Comprehensive Organic Functional Group Transformations, Volume 6 (Synthesis: Carbon with Three or...

Comprehensive Organic Functional Group Transformations, Volume 6 Elsevier, 2003 Editors-in-Chief: Alan R. Katritzky, Otho Meth-Cohn, and Charles W. Rees Synthesis: Carbon with Three or Four Attached Heteroatoms

Part I: Tetracoordinated Carbon with Three Attached Heteroatoms, RCXX′X″

6.01 Trihalides, Pages 1-33, Richard D. Chambers and John Hutchinson 6.02 Functions Containing Halogens and Any Other Elements, Pages 35-66, Graham B. Jones and Jude E. Matthews 6.03 Functions Containing Three Chalcogens (and No Halogens), Pages 67-102, Glynn Mitchell 6.04 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen, Pages 103-136, Martin J. Rice 6.05 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen), Pages 137-170, David P. J. Pearson 6.06 Functions Containing at Least One Metalloid (Si, Ge, or B) and No Halogen, Chalcogen or Group 15 Element; Also Functions Containing Three Metals, Pages 171-210, Vadim D. Romanenko, Michel Sanchez and Jean-Marc Sotiropoulos

Part II: Tetracoordinated Carbon with Four Attached Heteroatoms, CXX′X″X‴

6.07 Functions Containing Four Halogens or Three Halogens and One Other Heteroatom Substituent, Pages 211-247, Alex H. Gouliaev and Alexander Senning 6.08 Functions Containing Two Halogens and Two Other Heteroatom Substituents, Pages 249-270, Anastassios Varvoglis by kmno4

6.09 Functions Containing One Halogen and Three Other Heteroatom Substituents, Pages 271-293, Angela Marinetti and Philippe Savignac 6.10 Functions Containing Four or Three Chalcogens (and No Halogens), Pages 295-318, Alex H. Gouliaev and Alexander Senning 6.11 Functions Containing Two or One Chalcogens (and No Halogens), Pages 319-358, Wolfgang Petz and Frank Weller 6.12 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen), Pages 359-375, Duncan Carmichael, Angela Marinetti and Philippe Savignac 6.13 Functions Containing at Least One Metalloid (Si, Ge or B) and No Halogen, Chalcogen or Group 15 Element; Also Functions Containing Four Metals, Pages 377-406, Paul D. Lickiss

Part III: Tricoordinated Carbon with Three Attached Heteroatoms, Y=CXX′

6.14 Functions Containing a Carbonyl Group and at Least One Halogen, Pages 407-457, Geoffrey E. Gymer and Subramaniyan Narayanaswami 6.15 Functions Containing a Carbonyl Group and at Least One Chalcogen (but No Halogen), Pages 459-498, Heiner Eckert and Alfons Nestl 6.16 Functions Containing a Carbonyl Group and Two Heteroatoms Other Than a Halogen or Chalcogen, Pages 499-526, Anthony F. Hegarty and Leo J. Drennan 6.17 Functions Containing a Thiocarbonyl Group and at Least One Halogen; Also at Least One Chalcogen and No Halogen, Pages 527-567, Erich Kleinpeter and Kalevi Pihlaja 6.18 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms Other Than a Halogen or Chalcogen, Pages 569-585, José Barluenga, Eduardo Rubio and Miguel Tomás 6.19 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group—SeC(X)X′ and TeC(X)X′, Pages 587-599, Frank S. Guziec and Lynn J. Guziec 6.20 Functions Containing an Iminocarbonyl Group and at Least One Halogen; Also One Chalcogen and No Halogen, Pages 601-637, Thomas L. Gilchrist 6.21 Functions Containing an Iminocarbonyl Group and Any Elements Other Than a Halogen or Chalcogen, Pages 639-675, Ian A. Cliffe 6.22 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B or a Metal, Pages 677-724, Vadim D. Romanenko, Michel Sanchez and Lydia Lamandé

Part IV: Tricoordinated Stabilized Cations and Radicals, +CXYZ and ·CXYZ

6.23 Tricoordinated Stabilized Cations and Radicals, +CXYZ and ·CXYZ, Pages 725-734, Thomas L. Gilchrist 6.24 References to Volume 6, Pages 735-844 by kmno4

6.01TrihalidesRICHARD D. CHAMBERSUniversity of Durham, UK

and

JOHN HUTCHINSONBNFL Fluorochemicals Ltd., Durham, UK

5[90[0 GENERAL METHODS 0

5[90[0[0 The Addition of Haloèns and Interhaloèn Compounds to Fluoroalkenes 15[90[0[1 The Addition of Haloalkanes to Haloalkenes 3

5[90[0[1[0 Lewis acid!catalysed addition of trihalomethyl cations to haloalkenes*the Prins reaction 35[90[0[1[1 Additions initiated by free radicals\ heat or radiation 35[90[0[1[2 Additions catalysed by salts and complexes of transition metals 55[90[0[1[3 Additions induced electrochemically 6

5[90[0[2 The Preparation of C1 Chloro~uorohydrocarbons 6

5[90[1 TRIFLUOROMETHYL DERIVATIVES*RCF2 8

5[90[1[0 General 85[90[1[1 Aryl Derivatives 8

5[90[1[1[0 Conversion of `roups attached to an aromatic rin` into the tri~uoromethyl `roup 85[90[1[1[1 Substitution by tri~uoromethyl radicals 005[90[1[1[2 Substitution of hydroèn by the tri~uoromethyl `roup actin` as an electrophile 015[90[1[1[3 Substitution of haloèns by the tri~uoromethyl `roup actin` as a nucleophile 025[90[1[1[4 Substitution of haloèns by the tri~uoromethyl `roup usin` derivatives of metals 03

5[90[1[2 Derivatives of Alkanes\ Alkenes\ Alkynes and Other Saturated Compounds 055[90[1[2[0 Haloèn exchanè 055[90[1[2[1 Conversions of other `roups to the tri~uoromethyl `roup 085[90[1[2[2 Transfer of tri~uoromethyl `roups as radicals 195[90[1[2[3 Reactions involvin` tri~uoromethyl derivatives of metals and metalloids 11

5[90[2 TRICHLOROMETHYL DERIVATIVES*RCCl2 12

5[90[2[0 Trichloromethyl Groups Attached to an Aliphatic Centre 125[90[2[0[0 Conversion of `roups attached to an aliphatic centre into the trichloromethyl `roup 125[90[2[0[1 Transfer of the trichloromethyl `roup to an aliphatic centre 12

5[90[2[1 Trichloromethyl Groups Attached to an Aromatic Rin` 165[90[2[1[0 Conversion of `roups attached to an aromatic rin` into the trichloromethyl `roup 175[90[2[1[1 Transfer of the trichloromethyl `roup to an aromatic rin` 18

5[90[3 TRIBROMOMETHYL DERIVATIVES*RBr2 20

5[90[4 MIXED SYSTEMS WITH FLUORINE*RCF1Hal 21

5[90[5 MIXED HALOFORMS*CHXY1 AND CHXYZ 21

5[90[0 GENERAL METHODS

There are several general methods which can lead to trihalomethyl compounds where the halogenatoms can be the same or di}erent[ It will be seen that some of these methods lead to compounds

0

1 Trihalides

in which there are two such trihalomethyl groups[ For simplicity\ the general methods are discussed_rst[

5[90[0[0 The Addition of Halogens and Interhalogen Compounds to Fluoroalkenes

The addition of halogens and interhalogen compounds to ~uoroalkenes a}ords a valuable methodfor the preparation of compounds containing the group0CHal2 where the halogen atoms may be thesame or di}erent[ The addition of halogens is conveniently carried out under ultraviolet irradiation"Equations "0# and "1## ð30JA2365\ 57JOC0905Ł\ but the addition of iodine to tetra~uoroethene occursonly at elevated temperatures "Equation "2## ð38JCS1837\ 38JOC636\ 42JCS0437\ 52USP2965930Ł[ Generallythe yields of the adducts are high\ but when 0\0!di~uoroethene is treated with iodine a mixture ofcompounds is obtained\ the most abundant of which is CF2CH1I "Equation "3## ð47JOC211Ł[

Cl

ClF

F3C

Cl

F3C

F

Cl

Cl

ClCl2, UV

(1)

F

FF Br

F

F

Br

F

OH

RF

OH

RFBr2, UV(2)

F

FF I

F

F

F

I

F

i, I2, Et2O, 60 °C, 15 h; ii, I2, 150 °C, 24 h; iii, I2, KI, H2O, 100 °C, 5 h

i, ii or iiiF

(3)

(4)

F

I2, 185 °C, 16 hF

F

F

F

I

F

I

F

F

F

F

F

F I

+ + +

The addition of the interhalogen compounds ICl and IBr to ~uoroalkenes also can be used togive compounds having the group0CHal2[ With asymmetric alkenes\ the addition is regioselective\but the precise composition of the product is in~uenced by the reaction conditions and the presenceof catalysts[ The reactions shown in Equations "4#Ð"8# were carried out by several workers and thusunder di}erent sets of conditions ð41JCS3312\ 43JCS812\ 50JCS2668\ 50JA1384\ 51JOC0371\ 53JOC141Ł^ theyields and\ where more than one isomer was obtained\ isomer ratios were correspondingly di}erent[

F

F F

Cl F

FF

Cl

I Cl

F

FF

Cl

Cl I+ ICl (5)+

F

F F

F

FF

I

F

FF

Cl+ ICl (6)+Cl I

F

F Cl

F

ClF

I

F

ClF

Cl+ ICl (7)+Cl ClCl

Cl I

F

F F

F

FF

I

F

FF

Br+ IBr (8)+Cl ClCl

Br I

F

F

F

IF

Br+ IBr (9)

The elements bromine and ~uorine\ or iodine and ~uorine\ can be added to ~uoroalkenes bytreating the alkene with a mixture of bromine tri~uoride and bromine\ or iodine penta~uoride andiodine "Equations "09#Ð"11##[ Here\ {IF| refers to a stoichiometric mixture of iodine penta~uoride

2General Methods

and iodine "IF4¦1I104{IF|#\ and {BrF| to a stoichiometric mixture of bromine tri~uoride andbromine "BrF2¦Br102{BrF|#[ While the addition of {BrF| to ~uoroalkenes is vigorous and needsto be moderated\ the corresponding reactions of {IF| are carried out at elevated temperaturesð50JCS2668Ł\ and catalysts may be added ð50JA1272\ 73JAP4840114Ł[ The addition of {IF| to tetra!~uoroethene is particularly important because the product\ penta~uoroiodoethane\ is a startingmaterial in one of the commercial routes to ~uorochemical surfactants and surface treatments ðB!68MI 590!90Ł[ Additions to hexa~uoropropene and 0\0!di~uoroethene give single isomers\ butadditions to chlorotri~uoroethene and 0\0!dichlorodi~uoroethene yield mixtures of isomers whosecomposition is related to the reaction conditions[ The reaction of {IF| to tetrachloroethene resultsin ~uorination only "Equation "07##[ For the addition of {IF| to internal alkenes with the formulaCF2"CF1#nCF1C"CF2#1\ special procedures are necessary "Equation "11##[ Either potassium ~uoridemust be added to the {IF| mixture\ or the alkene may _rst be treated with AgF or AgF:KF in apolar aprotic solvent to make the silver salt\ which in turn is treated with iodine to give the desiredproduct ð76JFC"26#112Ł[ These products are tertiary per~uoroiodoalkanes and are highly toxic\ sospecial care must be taken during their preparation[

(10)

F

F

F

FF

F+ 'IF'F

F F

I

(11)

F

F3C

F

FF3C

I+ 'IF'F

F F

F

(12)

F

F

F

FF

F+ 'IF'F

Cl Cl

I +F

FF

I

Cl

F

(13)

F

F

F

ClF

F+ 'IF'Cl

Cl Cl

I +F

ClF

I

Cl

F

(14)

Cl

F

Cl

FF

I+ 'IF'F

Cl Cl

F

(15)

F

F

F

ClF

F+ 'IF'Cl

I

(16)

F

F

F

FF

F+ 'IF'F

I

(17)

F

F

F

IF

F+ 'IF'

(18)

Cl

Cl

F

ClCl

Cl+ 'IF'Cl

Cl F

Cl

(19)

F

F

F

FF

F+ 'BrF'F

F Br

F

(20)

F

F3C

F

F3C F

F+ 'BrF'F

F Br

F

3 Trihalides

(21)

F

F

Cl

F F

F+ 'BrF'F

Cl F

Br +Cl

F F

Br

F

F

(22)

F

CF3(CF2)n

I

CF3(CF2)n CF3

CF3+ 'IF'CF3

CF3 F

F

5[90[0[1 The Addition of Haloalkanes to Haloalkenes

The addition of haloalkanes to haloalkenes can be used to generate alkanes which bear a tri!halomethyl group "Equation "12##[ If the alkene is perhalogenated\ then it can be seen that theadduct will have two trihalomethyl groups[ These addition reactions can be initiated in four mainways\ that is\ by Lewis acids\ by free radical initiators\ by salts and complexes of certain transitionmetals\ and electrochemically[

(23)XRX + R

5[90[0[1[0 Lewis acid!catalysed addition of trihalomethyl cations to haloalkenes*the Prins reaction

The aluminum chloride!catalysed addition of chloroalkanes to chloroalkenes has been knownsince the beginning of this century\ and is known as the Prins reaction ð03JPR304\ 24RTC138\ 24RTC296Ł[More recently\ the reaction has been extended to include the addition of chloro~uoromethanes to~uoroalkenes and chloro~uoroalkenes[ While most of the activity in this area occurred up to theearly 0869s\ and was reviewed by Paleta ð66FCR28Ł and by Paleta and Posta ð61CLY826Ł\ interesthas been renewed recently because the adducts may be intermediates in the manufacture of potentialreplacements for the higher!boiling chloro~uorocarbons "e[g[\ ð80MIP590!90\ 80EUP310211\ 81EUP362094\81JAP93053928Ł#[ Most commonly\ the halomethanes used in these reactions are CCl3\ CHCl2\ CFCl2and CFHCl1\ and these have been added to the alkenes CF11CF1\ CF11CFCl\ CF11CCl1\CFCl1CCl1\ CCl11CFCl\ C1Cl3\ CHCl1CHCl\ CF11CFH\ CF11CH1 and CF11CHCl "seeTable 0#[ The addition of halomethanes to asymmetric perhalogenated ~uoroalkenes proceedsnonregiospeci_cally\ but corresponding additions to the hydrogen!containing alkenes CFCl1CFH\CF11CFH\ CF11CH1 and CF11CHCl are highly regioselective\ with the electrophilic haloalkylgroup becoming attached to the carbon which bears the hydrogen[ This suggests that the preferredisomer is that in which most of the ~uorine atoms on the precursor alkene are attached to thecarbon where positive charge develops in the initial stages of the reaction[ In reactions with~uorotrichloromethane\ both C0F and C0Cl bonds are cleaved\ although cleavage of the C0Fbond is preferred due to the greater Al0F bond strength[ In its reaction with the alkenesCFCl1CHF and CF11CHCl the C0F bond is cleaved exclusively[ Some examples of thesereactions are given in Table 0\ where it can be seen how the approach can be used to give a varietyof propanes with various trihalomethyl groups attached to carbon atoms[ It is probable that theprimary products in each of these reactions undergo rearrangement or further reaction\ and thereforethe composition and nature of the observed products are dependent upon reaction conditions[

5[90[0[1[1 Additions initiated by free radicals\ heat or radiation

When subjected to heat\ light\ or free radical initiators such as peroxides or azo compounds\haloalkanes add to alkenes and haloalkenes "Scheme 0#[

Whether a simple adduct or a mixture of high molecular!weight telomers is obtained is determinedby the relative rates of the propagation\ transfer and termination reactions[ Thus\ compounds withthe weakest C0X bond\ that is\ iodides\ give lower molecular!weight products\ as do alkenes whichare di.cult to polymerize under the conditions of the reaction[ But if the alkene is easily polymerized\for example tetra~uoroethene\ or if the telogen is not particularly reactive\ high molecular!weight

4General Methods

Table 0 Lewis acid!catalysed addition of haloalkanes to haloalkenes[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐYield Composition

Reactants Conditions ")# Products ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐCFCl2 CF1CF1 ½14>C:2 h 69 CF2CF1CCl2\ CF1ClCF1CFCl1 72\ 06 60CCC0756CHFCl1 CF1CF1 04>C:2[4 h 47 CF2CF1CHCl1\ CF1ClCF1CHFCl 48\ 30 60CCC0756CFCl2 CF1CCl1 11>C:06 h 31 CF2CCl1CCl2\ CFCl1CF1CCl2\ 34\ 37\ 6 55CCC2473

CF1ClCCl1CFCl1CHFCl1 CF1CCl1 6>C:01 h 67 CFCl1CF1CHCl1\ 70\ 08 56CCC2777

CF2CCl1CHCl1\CCl2CF1CHFCl\CF1ClCCl1CHFCl\CF1ClCFClCHCl1

CFCl2 CF1CHF 9Ð03>C:6 h 54 CF2CHFCCl2\ CF1ClCHFCFCl1 69\ 29 63CCC0229CHFCl1 CF1CHF 9>C:6 h 72 CF2CHFCHCl1\ 47\ 31 63CCC0229

CF1ClCHFCHFCl*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Transfer

Termination

Scheme 1

RX R• + X•

or In2 2 In•

In• + RX R• + InX

R• + n R

•

n

R X

n

R

•

n

+ RX + R•

R

•

n

R

•

n

+ R R

2n

X• + X• X2

R

•

n

+ X• R X

Initiation

n

Propagation

material is obtained[ With easily polymerized alkenes\ the telomerization can be controlled by usinga large excess of the telogen "preferably an iodide or diiodide# and recycling the lower telomers[This addition of a haloalkane is often regioselective\ and it is observed that the incoming radicalgenerally attacks the least sterically hindered carbon[ However\ there is still debate on the factorswhich control the products of these reactions and the relative stability of the potential intermediateradicals\ and polar e}ects "note that trihalomethyl radicals are electrophilic# as well as steric e}ectsall play their part[

This approach is used in the manufacture of C7 or C8 per~uoroalkyl iodides\ which are inter!mediates in the preparation of per~uorocarbon surfactants and surface treatments ðB!68MI 590!90Ł[Illustrative examples of these addition reactions are given in Equations "13#Ð"24# "NB[ Highertelomers are also produced in these reactions# ð36JA0099\ 89JFC"36#150\ 49JA1102\ 42JOC217\ 42JCS811\42JCS2650\ 41JCS2389\ 53JOC0087\ 47JA740\ 76IZV797\ 44JA657\ 74T3492Ł "references refer to the respectiveEquations "13#Ð"24##\ but many more are recorded elsewhere ð52OR"02#80\ B!63MI 590!90\ B!65MI 590!90Ł[ It is noteworthy that\ unlike other polyhaloalkanes\ trichloromethane adds to alkenes byhydrogen transfer "Equation "15##[

5 Trihalides

CCl4 R+ClCl

RClCl (24)

F

RFCl

FClCl

RFF

F ClCCl4

F F

+ (25)

CCl3H n-C6H13+n-C6H13Cl

ClCl (26)

CCl3Br Ph+PhCl

ClCl (27)

Br

Cl

ClCl

I

F

FF

F

FFCCl3I (28)+

F

FF

FFF

FF

F ICF3I

F F

+ (29)

CN

CNF

IFFCF3I + (30)

OEt

OEtF

BrBrFCF2Br2 + (31)

F

F

F

F

F

F

F

F

F F

F

FF

BrCF2Br2 +

F Br

(32)

Br

BrF

F

FF

FF

BrCBr4 + (33)

Br

F

FF

ClFCF2BrCl

BrF+

F

(34)

CO2EtBr

CO2EtEtO2C

Cl

Cl

Cl

CCl3Br + EtO2C (35)

5[90[0[1[2 Additions catalysed by salts and complexes of transition metals

In 0845 ð45CI"M#260Ł\ unexpected results were obtained when the thermal additions of CCl3 andCCl2H to acrylonitrile were carried out using a steel autoclave[ More of the 0 ] 0 adduct was obtainedthan expected\ and trichloromethane gave the adduct CHCl1CH1CHClCN rather than

6General Methods

CCl2CH1CH1CN\ which is normally obtained in free radical additions to alkenes "vide supra#[Later ð52JCS0776Ł\ it was established that copper"II# and iron"III# both catalysed the addition oftetrachloromethane to a variety of vinylic monomers\ and that 0 ] 0 adducts were frequently the soleproducts\ even with easily polymerized alkenes[ This discovery led to extensive work in the area\and copper"II# has now been used to catalyse the addition of CCl3\ CCl2Br\ CCl1Br1\ CF2CCl2 andother chloro compounds to a large variety of alkenes and dienes[ It is worth noting that the additionof CF2CCl2 followed by hydrogenation of the adduct can be used to introduce a CF2CH1 group[While most investigations in this area have used copper! and iron!based catalysts\ other metal saltssuch as samarium diiodide ð89JCS"P0#1920Ł and vanadium dichloride ð89SL106Ł have been used morerecently[ As well as alkenes which contain only hydrogen\ halogenated alkenes and those whichcontain other groups have also been used[ Generally the 0 ] 0 adduct is the only product\ but highertelomers are produced when the alkene is halogenated[ However\ this method of initation alwaysgives lower molecular!weight material than the corresponding peroxide initiated reaction[ Aminesare often added to form complexes and {increase the solubility| of the copper\ and consequently toincrease the reaction rate[ The following is not a comprehensive list of references but will serve to leadthe reader into the area] ðB!63MI 590!90\ 64ACR054\ 65T1184\ 66TL3204\ 79CCC2377\ 79CCC2491\ 74PAC0716\76JPS"A#2914\ 78JFC"34#104\ 89JFC"36#84\ 80MI 590!90\ 81CCC0180\ 81JMOC40\ 82JFC"50#022Ł[

As well as metal oxides\ salts and their complexes with amines\ other transition metal complexessuch as carbonyls of iron ð56JCS"C#0049\ 79JOC2846Ł and cobalt ð69JOC1871Ł\ carbonyl complexes ofmolybdenum ð71JCS"D#1170\ 89JOM"286#40Ł\ iron ð89JOM"275#118Ł and chromium ð73JOM"159#C64Ł\and phosphine complexes of ruthenium ð62TL4036\ 64TL788\ 67JOC0623\ 74JOM"179#286\ 76JCS"P0#0404\81JOM40Ł\ rhodium ð70AG"E#364Ł\ rhenium ð76JCS"P0#0404Ł and palladium ð70CL0058\ 74T282Ł have allbeen found to be e.cient catalysts in this reaction[ When the chiral Ru2Cl3"diop#2 "diop\ 1\2!O!isopropylidene!1\2!dihydroxy!0\3!bis"diphenylphosphino#butane# was the catalyst\ chiral adductswere obtained ð76BCJ2576Ł[

Clearly the metal!catalysed additions of haloalkanes to haloalkenes proceed by a di}erentmechanism to those promoted by free radical initiators such as peroxides[ Any mechanism needs tobe able to explain the {abnormal| addition of trichloromethane\ the suppression of the propagationstep "0 ] 0 adducts are the main products#\ and the fact that the addition of tetrachloromethane tocyclohexene is highly stereoselective "with a ruthenium catalyst# compared with the situation whichobtains when conventional radical initiators are used[ It is unlikely that the details of the mechanismwill be the same for all the catalysts that have been identi_ed\ but it is generally believed that it isnot a simple redox process but one in which "e[g[\ for CCl3# a trichloromethyl radical is formed onand bound to the catalyst prior to the addition to the alkene which is itself coordinated to thecomplex[

5[90[0[1[3 Additions induced electrochemically

The free radical chain addition of various polyhalomethanes to alkenes has been initiated byelectrochemically in situ generated manganese salts used in a catalytic amount associated withan equimolecular amount of a manganese"III# oxidizable compound such as methyl cyano! oracetoacetate[ In particular\ tetrabromomethane\ bromotrichloromethane\ dibromodi~uoromethaneand n!heptadeca~uorooctyl iodide have been added to a variety of alkenes in high yield by thismeans "Equation "25## ð81TL102Ł[

R+ CX3Y

Mn(II)

anodic oxidationR

Y X

X X

(36)

CX3 = CBr3, Y = Br; CX3 = CCl3, Y = Br; CX3 = CBrF2, Y = Br; CX3 = C7F15, Y = I

5[90[0[2 The Preparation of C1 Chloro~uorohydrocarbons

The manufacture of saturated compounds having the general formula C1HxClyFz represents animportant part of the ~uorochemical industry[ These compounds "x�O# "chloro~uorocarbons*{CFC|s# have been used as refrigerants\ solvents and foam!blowing agents[ However\ because they

7 Trihalides

have been implicated in the destruction of ozone in the earth|s upper atmosphere\ they are beingreplaced\ under the terms of the Montreal Protocol\ by hydro~uorocarbons "y�O# "{HFC|s# and\for an interim period\ by hydrochloro~uorocarbons "{HCFC|s#[ The manufacture of thesecompounds is largely brought about by treating a chlorocarbon with hydrogen ~uoride andsometimes chlorine[ Other reactions in the process may include isomerization and hydrogenation[The ~uorinations are carried out in either the liquid phase using an antimony"V# catalyst"Swarts| catalyst# or in the gas phase using a chromia!based catalyst[ The main routes to the C1

chloro~uorocarbons and those compounds which are replacing them are outlined in Scheme 1[0\0\0\1!Tetra~uoroethane "R023a# is to be the main {high!temperature| refrigerant "e[g[\ mobile airconditioning\ and domestic and industrial refrigeration# while 0\0\0!tri~uoroethane "R032a# and0\0\0\1\1!penta~uoroethane "R014# will be used in compositions for {low!temperature| refrigerationand static air conditioning "e[g[\ ð82MI 590!90Ł#[ As well as having the uses outlined above\ some ofthese compounds are intermediates in the manufacture of products such as the anaesthetic halothane"CF2CHClBr#\ and monomers such as 0\0!di~uoroethene and chlorotri~uoroethene[

Cl

ClCl

F

ClF

F

F

FF

F

F

ClF

F

Br

Cl

ClCl

Cl F

ClF

Cl

Cl

F

F

FF

Cl

F

Cl

F

FF

F

F

Cl

F

ClF

F

Cl F

FF

F

FF

ClF

F

Cl

Cl

F

ClF

F

Cl

F

F

FF

F

F

F

F

R133a

Cl

F

Halothane

Cl

R141b

Cl

F

R115

F

R123

R142b

F

F

R125

F

R113a

R114a

R143a

+ +

R113

R134a

R114

Cl

Cl

R134a R143a

Scheme 2

8Tri~uoromethyl

5[90[1 TRIFLUOROMETHYL DERIVATIVES*RCF2

5[90[1[0 General

There is a very considerable literature relating to the synthesis of organic compounds containingthe tri~uoromethyl group\ and this stems principally from the importance of such compounds inthe plant protection industry ð80MI 590!91Ł and\ to a lesser extent\ the pharmaceutical industry ðB!80MI 590!92\ B!71MI 590!90Ł[ Amongst other e}ects\ the introduction of the tri~uoromethyl groupincreases the lipophilicity of bioactive molecules\ enhancing transport across cell walls\ and canreduce metabolism of a drug[ A major review ð81T5444Ł is focused on the synthesis of tri~uoromethylderivatives\ and others ð80T2196\ 81T078\ 83TA826Ł include discussions of relevant methodology[ Inconsidering this area\ it is appropriate to draw attention to the fact that processes which involvehalogen exchange for ~uorine\ using anhydrous hydrogen ~uoride "AHF# as the source of ~uorine\will be the most economically favourable for large!scale manufacture by industry\ which is remark!ably adept at handling AHF[ Such procedures are not\ however\ particularly easy on the laboratoryscale\ and other approaches described here will frequently be preferred[ Furthermore\ the sensitivityof the molecule under consideration may well dictate the route that is most appropriate[

The considerations described above relate to compounds containing the tri~uoromethyl group asthe only halocarbon unit\ but\ of course\ there is a very wide range of applications for more highly~uorinated systems\ including their use as refrigerants and for other volatile inert ~uid applications\membranes\ polymers and anaesthetics[

5[90[1[1 Aryl Derivatives

5[90[1[1[0 Conversion of groups attached to an aromatic ring into the tri~uoromethyl group

Only the most reactive of organic halides will react with anhydrous hydrogen ~uoride withoutcatalysis "see Section 5[90[0[2#\ but benzotrichloride is converted to the tri~uoride "Equation "26##ð41MI 590!90Ł\ and analogous systems\ including heterocyclic compounds\ may be obtained in thisway "Equation "27## ð70AHC"17#0Ł[ More sophisticated techniques have been used in processes tochloro~uorinate side chains in a continuous process "Equation "28## ð79GEP2997970Ł[ Alternatively\antimony tri~uoride may be used in classical ~uorination processes "Equation "39# ðB!65MI 590!91Ł\where the product is obtained by simply distilling from the ~uorinating agent\ but the trichloroethylmoiety is much less e.cient for conversion to the tri~uoroethyl group "Equation "30## ð77JOC2526Ł[A clever {one!pot| methodology is available for acid!induced trichloromethylation accompanied byexchange of chlorine for ~uorine "Equation "31## ð70JFC"07#170Ł[

AHF

40 °C, autoclave70%

CCl3 CF3

(37)

CCl3

N

CF3

NCCl3 CF3

HF

204 °C45%

(38)

Cl2, HF

300–600 °C33%N N Cl

F3C

(39)

SbF3

125 °C58–66%

CCl3 CF3

(40)

09 Trihalides

NO2 NO2NO2 NO2

CCl3 CF3

SbF3

SbCl5+ +

48%

Cl

FCl

ClCl

Cl

10% 33%

(41)

HF, CCl4CF3

α : β = 2 : 3

(42)

One of the most versatile methods available for introducing the tri~uoromethyl group involvesreactions of benzoic acid derivatives and corresponding heterocyclic compounds with sulfurtetra~uoride "Equations "32#\ "33# and "34## ð74OR"23#208\ 70AHC"17#0\ 76JOM"214#02\ 82JFC"59#122Ł\or the more convenient but less reactive diethylaminosulfur tri~uoride "DAST# ð64USP2803154\65USP2865580Ł and related systems "Equation "35## ð77OR"24#402Ł[

SF4, 150 °C

6 h

CO2H

CO2HHO2C

CF3

CF3F3C

33% conversion

(43)

(44)

CF3F3C

CF3F3C

F3C

F3C

O

FF

FF

O

FF

FF

O

FF

FF

+ +

66–76% 8–12% 0.8–1.7%

CO2HHO2C

CO2HHO2CSF4, 150–200°C

16 h

SF4, HF

80–140 °Cautoclave55–92%

CO2H CF3

XX

X = OMe, Me, H, Cl, NO2

(45)

Et2NSF3

NaF50%

CO2H CF3

(46)

Thio derivatives "e[g[\ ortho!thioesters# may also be used for conversion to the tri~uoro!methyl moiety\ using NBS\ or its equivalent\ followed by pyridineÐhydrogen ~uoride "Equation"36## ð75TL3750Ł[ Dithiocarboxylate esters are converted in a similar process "Equation "37##ð81CL716Ł\ and dithiocarboxylate derivatives are also converted in an interesting process thatinvolves xenon di~uoride "Equation "38## ð89TL2246Ł[ A very unusual conversion of a nitrile to thetri~uoromethyl derivative occurs\ using carbonyl ~uoride\ accompanied by other products "Equation"49## ð67IJ018Ł[

00Tri~uoromethyl

i, DBH

ii, HF–pyridine

C(SMe)3 CF3

NO2NO2

DBH = 1,3-dibromo-5,5-dimethylhydantoin

(47)

34%

DBH, Bu4N+H2F3–

CS2Me CF3

(48)

i, Mg, Et2O ii, CS2

iii, XeF2 40–77%

CF3

X

Ar-X

Ar = Ph, p-MeC6H4, m-CF3C6H4, α-naphthyl X = halogen (e.g., Br)

(49)

CN CF3

HF, NaF

4 d, 50 °C20%

+ COF2 (50)

5[90[1[1[1 Substitution by tri~uoromethyl radicals

Primary sources of tri~uoromethyl radicals include tri~uoroethanoic acid and tri~uoro!methanesulfonic acid\ but iodo! or bromotri~uoromethanes are important sources that have beenused extensively[ Various methods have been applied to generate tri~uoromethyl radicals from thesesources ð81T5474\ 80TL6414Ł\ and these radicals are\ of course\ electrophilic in character[ Conse!quently\ a wide range of radical aromatic substitutions occur\ and these probably proceed moree}ectively with the more electron!rich aromatic compounds\ but\ in general\ they are not high!yielding processes "Equations "40#Ð"47## ð70JFC"06#234\ 76CC0690Ł[

hν

DMF24%

+ CF3IO CF3O

(51)

hν+ CF3I N

NH

NNHN

NH

CF3

F3C+

32% 47%

(52)

Br Br

+ CF3ICF3

61%, o : m : p = 40 : 30 : 22

(53)

NH2 NH2

+ CF3BrCF3

(54)Zn, SO2

56%, o : p = 1.8 : 1

01 Trihalides

OH OH

+ CF3SO2NaCF3

ButOOH

Cu(II)

45%, o : m : p = 4 : 1 : 6

(55)

+ (CF3CO)2O70 °C

54%C6H6 C6H5CF3 (56)

X CF3XX = O (53%), NH (65%)

(57)[CF3(CO)O]2

O

HN

NH

CF3CO2H

electrolysis60%O

O

HN

NH

O

CF3(58)

Bis"tri~uoroacetyl# peroxide decomposes thermally and can be used to tri~uoromethylate elec!tron!rich aromatic compounds "Equations "48# and "59## ð89JFC"35#312Ł[ An atmosphere of ammoniahas been used to promote the reaction of iodotri~uoromethane with pyridine "Equation "50##ð68JAP68172Ł[ Remarkably\ some cross!coupling between hexa~uorobenzene and bromotri~uoro!methane occurs over copper chromite "Equation "51## ð82JFC"50#0Ł\ and\ in other high!temperaturechemistry\ polytetra~uoroethylene is used as a source of di~uorocarbene\ which\ under the con!ditions used\ is able to insert into carbonÐ~uorine bonds "Equation "52## ð58IZV085\ 63JCS"P0#097Ł[

60 °C

72%+ [CF3(CO)O]2

S CF3S(59)

CF370 °C

71%+ [CF3(CO)O]2 (60)

N N

CF3NH3

180 °C, 24 h60%

+ CF3I

α : β : γ = 46 : 40 : 13

(61)

+ CF3Brcopper chromite

600 °C, flow40%

C6F6 C6F5CF3 (62)

N

F + (–CF2–)n550 °C

N

F

F3C CF3

+

N

F

CF3

(63)

6% 60%

5[90[1[1[2 Substitution of hydrogen by the tri~uoromethyl group acting as an electrophile

Nucleophilic attack at a saturated carbon contained in a highly halogenated system is\ in general\very di.cult\ but Umemoto and co!workers have demonstrated that with superior leaving groupsit is possible to e}ect what is\ formally\ nucleophilic attack on the tri~uoromethyl group "Equation"53##[ Very powerful per~uoroalkylating agents are available through so!called {FITS| reagents""per~uoroalkyl#phenyliodonium iodides# ð73TL70\ 75JFC"20#26Ł[ So far\ the corresponding reagents

02Tri~uoromethyl

are not available for the introduction of the tri~uoromethyl group\ although this may be a practicaldi.culty\ rather than a fundamental di}erence in reactivity between tri~uoromethyl and otherper~uoroalkyl systems[ However\ a less powerful but e}ective series of salts of tellurium\ seleniumand sulfur heterocycles has been developed which will transfer the tri~uoromethyl moiety ð82JA1045Ł\and it is concluded that the process involves nucleophilic attack on the tri~uoromethyl group[ Theoverall process is illustrated in Scheme 2\ where the reactivity of the salts "0# varies in the seriesX�Te³Se³S\ while electron!withdrawing substituents in the aromatic ring also increase reac!tivity "1#[ Examples of tri~uoromethyl transfer from the salts "0# are shown "Equations "54#Ð"56##[The tri~uoromethylation of hydroquinone "Equation "55## e}ectively rules out a free radical processbecause hydroquinone is known to be an e.cient radical scavenger[

[Ar H] + F3C L [ArHCF3]+ + L– ArCF3 + H+ + L– (64)

XCF3X–

+ CF3IF2, CF3SO2OH

0 °C

X

CF3

+X

CF3

+

NO2O2N

(1) (2)

CF3SO2–

CF3SO2ONO2

Scheme 3

X = S, Se, Te

CF3OH

OH

CF3

OH+

52% 6%

+ (2) (X = S)

i, DMF (+ 4-dimethylaminopyridine)

(65)i

OH

+

61% 11%

+ (2) (X = S)i

OH

OH OH OH

OH

CF3

(CF3)2

i, DMF (+ pyridine)

(66)

+ (1) or (2)

NH2 NH2

CF3

Reactant(1) (X = S)(2) (X = S)

Conditions80 °C, 1 hRT, 0.5 h

Productso-CF3 (31%) + p-CF3 (15%)o-CF3 (54%) + p-CF3 (20%)

(67)

5[90[1[1[3 Substitution of halogens by the tri~uoromethyl group acting as a nucleophile

Tri~uoromethyllithium and !magnesium derivatives are unstable and\ therefore\ a methodologyfor the transfer of a tri~uoromethyl anion to electrophilic centres via silanes has been developed"Equation "57## ðB!81MI 590!90Ł[ A convenient synthesis of trimethyltri~uoromethylsilane has been

03 Trihalides

reported "Equation "58## ð79ZOB0786\ 73TL1084\ 82RHA121\ 81MI 590!91Ł\ and a process using tetra!kis"dimethylamino#ethene has also been described "Equation "69## ð78JFC"31#318Ł[ The key stepinvolves displacement of the tri~uoromethyl group from silicon\ using tetrabutylammonium ~uoride"which inevitably contains amine#[ Understandably\ reaction only occurs with the more activatedaromatic systems "Equations "60# and "61## ðB!81MI 590!92Ł[

+ Ar LCF3– [ArLCF3]– ArCF3 + L– (68)

TMS-Cl + CF3Br + (Et3N)3P TMS-CF3PhCN

(69)

Me2N

Me2N NMe2

NMe2

+ TMS-Cl TMS-CF3

PhCN

or CH2Cl2(70)

tbaf, 0 °C, 0.5 h, RT

NO2

(71)F C6F5NO2 + CF3C6F4NO2 + TMS-CF3

90% 10%

+ TMS-CF3

F

mixture of trifluoromethylated products

NO2

NO2

tbaf, 0 °C, THF(72)

5[90[1[1[4 Substitution of halogens by the tri~uoromethyl group using derivatives of metals

As indicated above\ lithium and magnesium derivatives are unstable and\ therefore\ are not viablereagents for the introduction of the tri~uoromethyl group[ Metals that form weaker bonds to~uorine generally give more stable tri~uoromethyl derivatives\ and consequently copper\ cadmiumand zinc compounds are particularly useful in synthesis ð81T078\ 81T5444Ł[ Therefore\ access totri~uoromethyl derivatives of these metals is of some importance[ Easily accessible sources for thee}ective use of the tri~uoromethyl moiety include CF2CO1H\ CF2SO1OH\ CF2I "usually made fromtri~uoroacetic acid by Hunsdiecker processes#\ CF2Br and CF1Br1[

Tri~uoromethylation of aryl halides occurs using CF2I or CF2Br in the presence of copper powderin aprotic solvents at elevated temperatures "Equation "62## ð79JCS"P0#1644Ł\ but direct reaction ofsodium tri~uoroacetate with CuI in N!methyl!1!pyrrolidone "NMP# is also possible ð70CL0608Ł\ andit has been concluded that the reaction proceeds via an intermediate like ðCF2CuIŁ=− rather thanðCF2CuIŁ = "Equations "63#Ð"65## ð77JCS"P0#810Ł[ Tri~uoromethanesulfonyl chloride can be used inan analogous way "Equation "66## ð78JFC"34#75Ł[

N

N HMPA

46%+ CF3Cu

NI

NH2

O

NAcO

AcO OAc

N

N

NCF3

NH2

O

NAcO

AcO OAc

HMPA = hexamethylphosphoramide

(73)

I CF3

CF3CO2Na, Cu, NMP

160 °C, 4 h98%

Cl Cl

(74)

04Tri~uoromethyl

41%

CF3CO2Na, Cu, NMP

160 °C, 4 h

Br

BrBr

CF3

CF3F3C

CF3

CF3

48%

+ (75)

CF3CO2Na, Cu, NMP

160 °C, 4 h85%N Cl N Cl

I F3C

(76)

Cl

NO2

NO2

+ CF3SO2ClCu, DMF

100 °C73%

CF3

NO2

NO2

(77)

A fascinating route to tri~uoromethylcadmium and !zinc has been developed by Burton and co!workers ð74JA4903Ł in which reaction of dihalodi~uoromethanes with cadmium or zinc powders inDMF gives stable solutions of the corresponding tri~uoromethyl derivatives "Scheme 3#\ which thenreact further[ Copper reacts in an analogous way but a mixture of homologues is obtained unless~uoride ion is added\ or other procedures used to prevent the di~uorocarbene generated reactingfurther with CF2MX "Scheme 3#[ Cadmium derivatives can also be converted to copper reagentsð75JA721Ł\ and these can be stabilized against formation of higher homologues by adding HMPAð78JA7491Ł "Equations "67# and "68##[ Tri~uoromethylation in dimethylacetamide "DMA# is alsoe.cient "Equation "79## ð77CC527Ł[ Transfer of the tri~uoromethyl group to amines\ using dibromo!di~uoromethane\ has also been reported ð80JFC"41#118Ł "Equation "70##[ Methyl ~uoro!sulfonyldi~uoroacetate in the presence of copper"I# iodide functions in a similar way ð78JCS"P0#1274Ł\and the corresponding iodide has also been used "Equations "71# and "72##[ The source of thestarting materials in the latter cases is tetra~uoroethene\ via formation and ring opening of a b!sulfone "Scheme 4# ð59JA5070Ł^ this is an attractively direct but\ unfortunately\ potentially hazardousprocess for laboratory application[

Me2N

F

F+ CO

DMFMXY + [CF2]

Me2NF

+ F–

CF2XY + MDMF, RT

80–95%[CF3MX + (CF3)2M]

Scheme 4

F– + [CF2] CF3–

CF3– + MXY CF3MX + (CF3)2M

CF3CuX + [CF2] CF3CF2CuX[CF2]

etc.

[CF3CdX + (CF3)2Cd]CuY

–40 °C90–100%

[CF3Cu]

Y = I, Br, Cl, CN

X = Br, Cl; Y = Br, Cl; M = Cd, Zn, Cu

05 Trihalides

I

NO2 + CF3Cu DMF

HMPA70 °C, 4–6 h

75%

CF3

NO2 (78)

+CF3Cu DMF

HMPA70 °CS

I

I

I

I S

CF3

CF3

F3C

F3C

(79)

Cl

NO2

NO2

+ CF2Br2

Cu, DMA

100 °C, 4 h93%

CF3

NO2

NO2

(80)

CF2Br2 + + R2NHMe2N

Me2N NMe2

NMe2

R2NCF3 (81)

I

NO2

+CuI, DMF

60–80 °C, 3 h80%

CF3

NO2

(82)FO2SCF2CO2Me

PhF

FFPh BrICF2SO2F +

Cu, DMF

80 °C83%

(83)

SO2OF

F F

F+ SO3

FF F

F

FCOCF2SO2FF–< 80 °C

~3 atm93%

Scheme 5

5[90[1[2 Derivatives of Alkanes\ Alkenes\ Alkynes and Other Saturated Compounds

5[90[1[2[0 Halogen exchange

These reactions ð52AFC"2#070\ B!78MI 590!90\ 30JA2367\ 36JA0719Ł involve\ essentially\ the nucleophilicdisplacement of other halogens by ~uorine using a metal ~uoride ðB!62MI 590!90\ B!65MI 590!92Ł\frequently in combination with hydrogen ~uoride[ An important part of the function of the metal~uoride is to act as a Lewis acid\ to assist the removal of the halogen as a halide ion[ Some of thereactions could involve carbocations "Scheme 5#[

As the number of ~uorine atoms attached to the chlorine!bearing carbon increases\ it becomesprogressively more di.cult to e}ect further ~uorination "Equation "73# and "Scheme 6##[ Never!theless\ the inhalation anaesthetic CF2CHBrCl may be obtained by an exchange process "Scheme7# ð46BRP656668Ł[ For a carbocation!type process\ it is understandable that the introduction ofunsaturated sites makes such exchange reactions much easier "Equations "74# ð30JA2367Ł and "75#ð36JA0719Ł#[ Fluorination of hexachlorobutadiene provides an accessible route to hexa~uoro!1!butyne "Equations "75# and "76## ð38JA187Ł[ Functional derivatives are also accessible by theseprocedures\ for example halo!ethers and !thioethers "Equation "77## ð41JA2483Ł as well as hexa!~uoroacetone\ which is made commercially by this route "Equation "78## ð53FRP0258673Ł[ Antimony~uorides and various other ~uorides have been used to promote exchange with hydrogen ~uoride\

06Tri~uoromethyl

Cl + MFx

+ [MFxCl]–

F + MFx-1Cl

Cl

F

MFx-1

δ –δ +

or

F– (HF)

Scheme 6

and very e.cient catalysts have been developed by industry\ including chromia catalysts for use invapour phase processes^ these are particularly important in the refrigerant industry "see Section5[90[0[2#[

CCl4HF, SbCl3, Cl2

110 °C, 3 atmCCl3F + CCl2F2 + CClF3 (84)

9% 90% 0.5%

CCl3CCl3 CCl3CCl2F CCl2FCCl2F CCl2FCClF2 CClF2CClF2 CF3CClF2

Scheme 7

Scheme 8

CCl3Me CF3Me CF3CH2Cl CF3CHBrClHF, SbF5 Cl2 Br2

425–475 °C

Cl

Cl

Cl

Cl

Cl

Cl

Cl

ClCl

F

F

F

Cl

ClCl

F

F

ClSbF3

150 °C+

28%43%

(85)

Cl

Cl

F

F

FF

FF

Cl

F

F

F

FF

FF

+

ClCl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

ClCl

ClCl

SbF3Cl2

(86)

Cl

Cl

F

F

F

F

F

F

F F

F

F

F

F

Zn, Ac2O

63%(87)

07 Trihalides

SMe

Cl

Cl

Cl SMe

F

F

FSMe

Cl

Cl

+SbF3, SbCl5

90 °C 73%(88)

O

Cl

ClCl

Cl

ClCl

O

F

FF

F

FF

HF, 350 °C

Cr (cat.)(89)

Alkali metal ~uorides\ although easily used\ have limited application for saturated sites "Equation"89## ð52JOC001Ł\ but such systems are extremely e}ective for attack at unsaturated sites "Equation"80##\ where even lithium ~uoride\ normally the least reactive of the alkali metal ~uorides\ can givesome ~uorination "Equation "81## ð48JA1967\ 59JA2980Ł[ These reactions probably involve nucleo!philic attack with allylic rearrangement\ and other metal ~uorides will also promote this process"Equation "82## ð59BRP712408Ł[ Terminal ~uorinated alkenes are rearranged to the thermo!dynamically more stable isomers by the ~uoride ion "Equation "83## ðB!62MI 590!91Ł[ Furthermore\hexa~uorobutadiene is converted into hexa~uoro!1!butyne by ~uoride ion "Equation "84##ð50JA0656Ł and\ more surprising\ hexa~uorocyclobutene also gives hexa~uoro!1!butyne when passedover hot caesium ~uoride or potassium ~uoride "Equation "85## ð68CC853Ł[ An even more remarkablerearrangement induced by hot metal ~uorides involves conversion of per~uorobicyclobutylidene toa product containing three tri~uoromethyl groups "Equation "86##[

Cl Cl

ClCl

ClCl

ClClF F

FF

FF

ClCl

KF, 190 °C

NMP~60%

(90)

(C2H5)4NF, CHCl327 °C, 12 h

90%(91)

Cl F

FFCl

F Cl

FFF

LiF, cellosolve(92)

Cl F

FFCl

F F

FFF

F F

HF, CoF2, 250 °C

90–95%(93)

Cl Cl

Cl

F

FF

F C4F9

FF

F

F

+ F–F

FF

F

–

F F

CsF, 100 °C

no solvent

F– +

F C4F9

FF

F

FF

F C4F9

F

F

FF

F– +

(94)C3F7

F

F –

FF

F

F

F

F

F

F

F

F

F

F+

CsF, 100 °C, no solvent+ F

– (95)

08Tri~uoromethyl

F F

F

F

F

F

i

i, CsF or KF, 510–590 °C, flow system in N2

80–90%(96)F

F

F

F

F

F

F

i

70%F

F

F

F F

F

F F

F

FF

i, KF, 510 °C, flow system in N2

(97)

F

F

5[90[1[2[1 Conversions of other groups to the tri~uoromethyl group

Use of sulfur tetra~uoride ð59JA432Ł to convert the carboxyl group to the tri~uoromethyl groupproceeds well\ except where formation of anhydrides is in competition "Equations "87# and "88##ð67PJC60Ł and in some cases other functional groups present also react preferentially "Scheme 8# ðB!78MI 590!91Ł[ Treatment of ~uorinated enols with DAST gives tri~uoromethyl derivatives with ahigh degree of regio! and stereoselectivity "Equation "099## ð80TL4852Ł[ An interesting in situelectrophilic formylation and subsequent reaction with sulfur tetra~uoride has been reported "Equa!tion "090## ð71ZOR117Ł[

F F

FF

FF

( )8

HO2C CO2H( )8

SF4, 120 °C, 6 h

87%(98)

F F

FF

FF

( )3O

F

F F

F

( )3

(99)

SF4, 5 °C, 48 h

F

FF

( )3 O

FF FF

F

FF

( )3

+ +

HO2C CO2H

34% 10% 16%

COFF

FF F F

F

FF F F

F

FF

O

HO2C CO2H + SF4

100 °C

50%

HF, 20 °C

60%

Scheme 9

FPh

OH F+ Et2NSF3

Ph F

FF (100)

CF3

SF4, HCO2H, HF(101)

Although halogen exchange to form the tri~uoromethyl group proceeds well "see above#\ pro!cedures to convert the methyl group to the tri~uoromethyl moiety directly are limited[ High!valencymetal ~uorides\ for example cobalt tri~uoride\ will carry out this conversion at high temperatures\

19 Trihalides

but the rest of the molecule is also ~uorinated in the process\ leading to very useful inert ~uids"Equation "091## ð59AFC"0#055Ł[ Various direct ~uorination procedures can also be used for suchtransformations "Equation "092## ðB!62MI 590!92Ł[

CoF3

FF

CF3

(102)

F2

Au on Cu

CF3

CF3

F(103)

Electrochemical ~uorination "ECF# is a procedure for converting C0H bonds to C0F bonds atthe anode of an electrochemical cell during the electrolysis of hydrogen ~uoride ð56FCR66Ł underconditions that do not generate elemental ~uorine[ The process is operated on an industrial scaleand is particularly e}ective for polar systems\ for example the synthesis of tri~uoromethanesulfonicacid "Scheme 09# and other functions "Equation "093# and Scheme 00#[ An interesting conversionof the amino group to the tri~uoromethyl group involves conversion to an azo derivative\ usingnitrosotri~uoromethane\ followed by photolytic elimination of nitrogen "Scheme 01# ð66AG"E#743Ł[

MeSO2F CF3SO2FECF

96%

H2OCF3SO2OH

Scheme 10

CS2 CF3SF5

ECF

90%(104)

Scheme 11

MeCOF CF3COFECF H2O

CF3CO2H

Scheme 12

C8H17NH2 + CF3NOhν

C8H17CF3NN

CF3

C8H1769%

5[90[1[2[2 Transfer of tri~uoromethyl groups as radicals

One of the most e}ective and e.cient procedures for transferring tri~uoromethyl radicals involvesthe use of iodo! or bromotri~uoromethane for addition to an unsaturated unit "see Section 5[90[0[1#[These are generally radical chain reactions\ and they proceed with very high e.ciency when arelatively nucleophilic centre is involved\ and a range of catalytic procedures have been developed\as illustrated in Table 1[

Electrolysis of tri~uoroacetic acid is a very direct and attractive route for generation of tri~uoro!methyl radicals[ Mixed Kolbe� processes lead to tri~uoromethyl derivatives by combination ofradicals "Equation "094## ð64CJC418Ł\ although the process is not e.cient[ Similarly\ addition oftri~uoromethyl radicals\ generated this way\ to alkenes and derivatives leads to mixtures of productswhere dimerization of the radical arising from addition of the tri~uoromethyl group can be asigni_cant pathway "Equation "095## ð63CC212\ 67JCS"P0#191Ł[ Products that arise from cyclization ofthe intermediate radical "Equation "096## ð80T438Ł and from di!addition have been observed "Equa!tions "097# ð68CJC1506Ł and "098# ð78TL098Ł#[ Enzymes have been used to promote radical additions

10Tri~uoromethyl

Table 1 Addition of halo~uoromethanes to alkenes[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐYield

Reactants Catalyst:conditions Product ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐCH1�CHSiMe2¦CF2I Ru2"CO#01 CF2CH1CHISiMe2 78 73TL292CH2CO"CH1#7CH� Et2B CH2OCO"CH1#7CHICH1CF2 75 78TL2048

CH1¦CF2ICH1�CHC5H02¦CF2Br NaSePh CF2CH1CH"SePh#C5H02¦ 15\ 23\ 20 80TL264\

CF2SePh¦PhSeSePh 80TL6314CH1�CHR¦CF2I Na1S1O3 NaHCO2 CF2CH1CHIR B!83MI 590!90CH1�CHR "R�Ph\ Ru"PPh2#2Cl1 CF2CH1CHClR 78CC0448

CO1Et\ alkyl#¦CF2SO1Cl*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

"Equation "009## ð77JOC1249Ł\ and it is probable that these are reacting as electron transfer agents\in the manner that various other transition metal systems behave[ Reactions of plasma!generatedradicals can be very e.cient "Scheme 02# ð68CC017Ł[

CO2HEtO2C + CF3CO2Helectrolysis

46%

EtO2CF

FF

(105)

F

FF

F

FF

F

FF

F FF

F FF

+ CF3CO2Helectrolysis

(106)+

major

+ +

+ CF3CO2Helectrolysis

NH

F

FF

F

FF

HN (107)

NEt

O

O

NEt

O

O

F

FF

F

FF

electrolysis

40%+ CF3CO2H (108)

CONH2

F FF

CONH2 F

F

+ CF3CO2H (109)

Felectrolysis

35%

urease

39%PhCF3I +

Ph

F

F

F

F

FF

(110)

CF3I CF3• CF3 +F3C

F3C

F3C I

F3C

F3C

F3CCI4

97%

plasma

1 : 3

Scheme 13

11 Trihalides

5[90[1[2[3 Reactions involving tri~uoromethyl derivatives of metals and metalloids

Electrophilic tri~uoromethylating agents "see Section 5[90[1[1[2# can be applied to transferringthe tri~uoromethyl group to an alkyne "Equation "000## ð89TL2468Ł\ and acidic sites derived fromalkyl pyridines may be tri~uoromethylated using tri~ic anhydride\ together with formation ofcorresponding tri~ates "Equation "001## ð72JOC0665Ł[

Se

CF3

+LiPh CF3Ph+

CF3SO2O–46%

(111)

62%

N N CH2OSO2CF3 N

5%

++ (CF3SO2)2O (112)

CF3

Nucleophilic tri~uoromethylation has been carried out directly with a system that is highlysusceptible to nucleophilic attack "Equation "002## ð89IZV380Ł\ although the nature of the inter!mediate is not clear[ Displacement of the tri~uoromethyl group from trimethyltri~uoromethylsilane\using the ~uoride ion "see Section 5[90[1[1[3#\ is applicable to a range of systems "Scheme 03# ðB!81MI 590!90Ł\ and\ used in conjunction with copper"I# salts\ trimethyltri~uoromethylsilane functionsas a tri~uoromethylcopper reagent which will tri~uoromethylate aryl\ benzyl and allyl halides"Equation "003## ð80TL80Ł[

F F

FF

FF

FFF

F FF

F F

FF

FF

FF

F FF

F FF

+ CF3Br/P[NC2H5)2]3

CH2Cl2, –78 °C, argon

45%(113)

CO2R2

F3C

HO

R1CO2R2

F3C

TMS-O

R1R1COCO2R2 + TMS-CF3

F–

THF

HCl

68–83%

R1 = alkyl, arylR2 = alkyl Scheme 14

R1X + CF3SiR23 R1CF3

KF, Cu(I)

DMF, 60–80 °C23–94%

(114)

Tri~uoromethylcopper reagents\ made by other routes\ react with various substrates "Equations"004# ð81CC42Ł\ "005# ð68TL3960Ł and "006# ð71CL0342Ł#\ and zinc reagents are also useful ð81T078Łin a variety of contexts[

BrPh CO2Me

F

Cl

+ F PhCF3

F–, CuI

84%(115)

(116)Ph

HMPA(CF3I + Cu)

65%Br + CuCF3

Ph F

FF

12Trichloromethyl

Zn, CuI

61%, (E):(Z) = 3:7+ CF3I F

FF

OH(117)OH

5[90[2 TRICHLOROMETHYL DERIVATIVES*RCCl2

5[90[2[0 Trichloromethyl Groups Attached to an Aliphatic Centre

Trichloromethyl compounds can be prepared either by converting an existing group into atrichloromethyl group or by introducing a trichloromethyl group on to a carbon atom in an existingmolecule "see also Section 5[90[0#[

5[90[2[0[0 Conversion of groups attached to an aliphatic centre into the trichloromethyl group

As with chloro~uorocarbons\ the manufacture of many chlorinated solvents is being phased out[Of these\ only 0\0\0!trichloroethane is relevant to this chapter[ Several routes are available\ and thechoice\ which makes use of permutations of chlorination\ hydrochlorination and dehydro!chlorination\ is outlined in Scheme 04[ Hydrochlorination is usually e}ected by Lewis acid catalysis"e[g[\ FeCl2#\ and dehydrochlorination by thermal cracking or by the action of base[ Chlorinationis catalysed by free radical sources in the liquid or gas phase[ The route chosen depends in part onhow much hydrogen chloride the operator is prepared to make[

ClCl Cl

Cl

Cl Cl

Cl

CH2H2C Cl

ClCl

Cl

Cl

Cl

ClC2H6

Scheme 15

5[90[2[0[1 Transfer of the trichloromethyl group to an aliphatic centre

"i# Preparation of trichloromethylalkanes

Trichloromethyl anions are an unstable species and decompose to give dichlorocarbenes[However\ the problem of their instability can be minimized by running reactions at low temperatureand by generating the trichloromethyl anion in the presence of the substrate[ Trichloro!methyllithium\ which can be made at about −099>C from trichloromethane and butyllithium inTHF\ reacts successfully with iodoalkanes at this same temperature to give a series of trichloromethylalkanes "Equation "007## ð89JOC0170Ł[

RCl

ClCl

R IBuLi, CHCl3, THF, –100 °C

HMPA(118)

–CH2R = –(CH2)nCH=CH2 (n = 2 or 3),

13 Trihalides

The trichloromethylation of activated alkyl halides can also be carried out by a cross!couplingreaction with tetrachloromethane in an undivided electrochemical cell with a sacri_cial anode[ Thepreferred anode is zinc\ with a stainless steel cathode\ and the preferred solvent is a mixture of THFand tetramethyl urea "Scheme 05# ð77TL0588Ł[

RX = PhCH2Br, MeCHClOCO2Et, BrCH2CO2Me, Me(CH2)9Br

Anode

Cathode

M Mn+ + ne–

CCl4 + 2e– CCl3– + Cl–

CCl3– + RX CCl3R + X–

Scheme 16

Trichloromethylated compounds can also be prepared by the action of trichloromethyl anionsgenerated by the action of a base on trichloromethane[ Thus\ by using catalytic amounts ofelectrochemically generated base\ a relatively stable anion is produced which reacts with a\b!unsaturated esters and nitriles to give the corresponding b!trichloromethyl adducts in good yield[The base is made by the electroreduction of 1!pyrrolidone in DMF using tetraalkylammonium saltsas supporting electrolytes "Scheme 06# ð89TL6070Ł[

N O

H

N O1

N O

–2

DMF R4N+ CCl3–CO2Me

CN

–

eg.

or

Cl CO2Me

+

ClCl

H2

+e–, 1.8 F mol–1

DMF, R4NXPt cathode

R4N+

Cl CN

CHCl3 +

ClCl

R = Et, X = OTs; R = Bun, X = BF4

R4N+

–

or

Scheme 17

b!"Trichloromethyl#nitroalkanes can be prepared in good yield by the reaction between trichloro!methyl anions\ generated from trichloromethyltrimethylsilane and caesium ~uoride "see also5[90[0[1#\ and nitroalkenes "Equation "008## ð80SC1078Ł[

R1

R2

NO2

R3

NO2

R3

Cl

ClCl

R1 R2

i, TMS-CCl3, CsF, THF, 25 °C

ii, H+(119)

R1

Bun

PhMeEtMe

R2

MeHHH

Me

R3

HHEtH

Me

Closely related to the trichloromethyl radical additions outlined in Section 5[90[0[1[2 is thereaction of trichloromethylsufonyl chloride with 0!alkenes in the presence of ruthenium complexessuch as dichlorotris"triphenylphosphine#ruthenium"II#[ In this reaction\ the elements of CCl2 andchlorine are added to the double bond in high yield under mild conditions with the extrusion ofsulfur dioxide ð72SUL020Ł[ When the chiral Ru2Cl3"diop#2 is the catalyst\ chiral adducts are obtainedð76BCJ2576Ł[

14Trichloromethyl

"ii# Preparation of a!trichloromethyl carbinols

a!Trichloromethyl carbinols are valuable intermediates for making compounds in which thetrichloromethyl group is preserved and also for making those in which the trichloromethyl group hasbeen transformed into other functions "e[g[\ ð60S020\ 71TL0598\ 77M0316\ 78S355\ 80RCR0207\ 81TL2324Ł#[Essentially\ their preparation comprises the formation of a trichloromethyl anion followed by itsattack on an aldehyde or ketone "Scheme 07#[

CCl3– + R1 R2

O

HO

R1

R2

Cl

Cl

Cl–O

R1

R2

Cl

Cl

Cl

CCl3–AcCl3

H+

Scheme 18

Carbonyl compounds have been treated successfully with trichloromethyllithium\ but becausethe reactions have to be carried out at −099>C\ only the more reactive carbonyls can be usedð53AG"E#402\ 56JOC0106\ 77M0316\ 89JOC0170Ł[ Reactions can be carried out at higher temperatures"−67>C# if lithium dicyclohexylamide is used to generate the trichloromethyllithium from trichloro!methane in the presence of the carbonyl "Equations "019#Ð"012##[ Equation "012# gives equally goodresults with tribromomethane in place of trichloromethane ð63JA2909Ł[

Ph2COHCCl3Ph2COi

ii

i, BunLi, CHCl3, –110 °C, THF/Et2O, petroleum ether; ii, H+

(120)

(121)(CF3)2COHCCl3(CF3)2CO i, BunLi, CHCl3, –100 °C, THF

ii, H+

i, BunLi, CHCl3, –100 °C, HMPA

ii, H+

R CHO R( )n (122)

COHCCl3( )n

RHHMe

n232

O CCl3HO

i(123)

i, Lithium dicyclohexylamide, CHCl3, –78 °C, THF, hexane

Trichloromethane and a base have been used extensively to generate the trichloromethyl anion[The base may be sodium or potassium hydroxide ð33JCS63\ 49JA4901\ 72M702\ 76JOC833Ł\ an alkalimetal alkoxide ð47CB1553\ 53JOC0037Ł\ or potassium ~uoride supported on alumina ð75TL2734Ł[ Theamount of base\ its nature and also the choice of solvent are particularly important when thecarbonyl compound is inclined to undergo an aldol condensation or the Cannizzaro reaction[Reactions are generally carried out below 9>C to help suppress dichlorocarbene formation[ Phasetransfer catalysts have been used in these reactions\ but they were only really successful with higheraldehydes and ketones ð79JOC4103\ 68TL0362Ł[

The thermal decomposition of sodium trichloroacetate in a solvent yields dichlorocarbeneð48PCS118Ł[ However\ the intermediate trichloromethyl anion can be trapped by aldehydes to yieldtrichloromethyl carbinols[ Under similar conditions\ anhydrides react to give trichloromethyl lactolsor their tautomeric keto acids "Equation "013## ð56JOC1055Ł[ Trichloromethyl carbinols are alsoobtained in high yield when\ in the presence of an aldehyde\ trichloroacetic acid decomposes inDMSO ð72CC172\ 73JCS"P1#0136\ 78JCS"P1#140Ł or HMPA ð89S216Ł\ or a 0 ] 0 mixture of the trichloro!

15 Trihalides

acetic acid and its sodium salt decomposes in DMF ð81TL2324Ł[ These reactions are successful withaliphatic as well as aromatic aldehydes[ They are less successful with ketones unless the ketone is"partially# ~uorinated and therefore more electrophilic\ in which case the yields are high ð81BAU269Ł[

O

O

O

CCl3

O

OH

O

O

O

CCl3HO

CCl3CO2Na

DME(124)

Trichloromethyl compounds of silicon and tin have been used as sources of trichloromethylanions in reactions with carbonyl compounds[ For example\ the reaction of trichloro!methyltrimethylsilane and trimethylsilyl trichloroacetate in the presence of the ~uoride ion witharomatic and aliphatic aldehydes ð74JA3974\ 76SC0936\ 77T3024Ł\ trimethylsilyl trichloroacetate in thepresence of potassium carbonate and 07!crown!5 with aromatic aldehydes and ketones ð74TL0064Ł\and tributyl"trichloromethyl#stannane with aliphatic and aromatic aldehydes ð64JOM"091#312Ł allgive the corresponding trichloromethylcarbinols in good yield "Equations "014#Ð"017##[ Equation"017# proceeds with equal success to give tribromomethylcarbinols when tribromomethyltributyltinis used instead of the trichloromethyl tin compound[

RCHOHO

R Cl

Cl

Cl i, TMS-CCl3, tas-F, THF, 0 °C

ii, H+(125)

R = Ph, n-C10H21, PhCH(Me); tas = tris(diethylamino)sulfonium

R1

R2

O

R1

R2

HO

Cl

Cl

Cl

R1

R2

i, CCl3CO2-TMS, F–, THF

ii, H+(126)

O

F = KF or tas-F

= cyclohexanone, benzaldehyde, pivaldehyde, 2-cyclohexenone, crotonaldehyde

R1

R2

O

R1

R2

HO

Cl

Cl

Cl

R1

R2

i, CCl3CO2-TMS, K2CO3, 18-crown-6

ii, H+(127)

O = e.g. benzaldehyde, 3,5-dichlorobenzaldehyde, 4-hydroxybenzaldehyde, cyclobutanone, cyclopentanone, cyclohexanone

(128)R

HO

Cl

Cl

Cl i, Bu3SnCCl3, 80 °C

ii, H+RCHO

R = Me, Et, Pri, Ph, PhCH = CH

The reductive addition of tetrachloromethane to aldehydes using a lead:aluminum bimetal redoxsystem has been reported to give high yields of trihalocarbinols[ While a variety of aliphatic andaromatic aldehydes give good yields\ ketones give less satisfactory results[ The use of bromo!trichloromethane instead of tetrachloromethane gives exclusively the same product "Scheme 08#ð78JOC333Ł[

A variety of aldehydes have been treated with trichloromethyl anions generated by the cathodicreduction of tetrachloromethane in trichloromethane[ Only relatively small amounts of tetra!chloromethane are used in this reaction\ since it is the trichloromethane which supplies the protonto the intermediate anion and thereby generates another trichloromethyl anion*steps "ii# and "iii#in Scheme 19[ The use of vinyl acetate instead of an aldehyde yields the acetate MeCH"OAc#CCl2ð70TL760\ 71TL0598\ 71TL3790Ł[ These same workers oxidized trichloromethyl carbinols with chromicoxide to give the corresponding trichloromethyl ketones ð71TL0598Ł[

16Trichloromethyl

RCHO + CX4

X

X

X

HO

RPbX2 (cat.)/Al, DMF

Pb(0) Pb(II)

Al(III) Al(0)

X = Cl or Br; R = alkyl, aryl

Scheme 19

R

–O Cl

Cl

Cl

R

–O Cl

Cl

Cl + CHCl3R

HO Cl

Cl

Cl

CCl4+2e–

CCl3– + RCHO

CCl3– + Cl–

+ CCl3–

(i)

(ii)

(iii)

Scheme 20

The other approach to making trichloromethyl carbinols is to start with trichloroacetaldehyde"chloral#[ This compound will condense with aromatic hydrocarbons with FriedelÐCraft catalysts"e[g[\ H1SO3\ HCl\ AlCl2\ BF2 and ZnCl1# ð12CB868\ 31JA1404\ 55CJC464\ 57CJC1122\ 79CJC374Ł or underthe in~uence of basic catalysts "e[g[\ potassium hydroxide\ potassium carbonate and pyridine#ð45CB1467\ 14JPR014\ 41CB890Ł to yield trichloromethyl carbinols[ Certain Grignard reagents will reactwith chloral to give trichloromethyl carbinols\ although reduction of the chloral to trichloroethanolcan be a problem "Equation "018## ð40M0997\ 45BSF0330Ł[ Finally\ silanes\ R!TMS\ in which thegroup R is electron!withdrawing\ have been shown to react with chloral in the presence of a Lewisacid to give the corresponding trichloromethyl carbinols "Scheme 10# ð64JOM"82#32Ł[

HO

R Cl

Cl

ClCHO

Cl

Cl

ClRMgBr + (129)

TMS-O

R Cl

Cl

ClCHO

Cl

Cl

Cl

HO

R Cl

Cl

ClAl, Ga or InCl3

R-TMS +MeOH

R = allyl, aryl, vinyl, ethynyl, propargyl

Scheme 21

5[90[2[1 Trichloromethyl Groups Attached to an Aromatic Ring

The high reactivity of trichloromethylarenes makes them valuable intermediates in the synthesisof acids and their derivatives\ heterocyclic compounds and the tri~uoromethyl group "which wehave seen is of great interest to the pharmaceutical and agrochemical industries#[ Similarly totrichloromethyl aliphatic compounds\ trichloromethylarenes may be made by converting a groupwhich is already attached to a ring into a trichloromethyl group or by transferring a trichloromethylgroup on to a ring[

17 Trihalides

5[90[2[1[0 Conversion of groups attached to an aromatic ring into the trichloromethyl group

Methyl groups in arenes can be trichlorinated using chlorine\ by a free radical mechanism"Equation "029## ð51HOU"4:2#624Ł[ 1! and 3!Methylpyridines and 1! and 3!methylquinolines are alsoreadily trichlorinated\ but here reactions are best carried out by passing the halogen into a solutionof the substrate in glacial acetic acid\ optionally acetic anhydride\ and sodium or potassium acetate\where the reaction is believed to proceed by an ionic process\ with the acetate acting as a baseð12JCS1771\ 28JCS670\ 40JCS0034Ł[ 2!Methylpyridine cannot be trichlorinated by this method\ but whenits vapour and chlorine are passed over a chromia catalyst\ pretreated with hydrogen ~uoride\ 2!trichloromethylpyridine is produced ð71EUP54247Ł in reasonable yield[

(130)Cl2

heat or UV

CCl3

While these methods are fairly general\ there are situations where other methods are necessary^for example\ in the preparation of methylbenzotrichlorides where chlorination of dimethyl com!pounds leads to chlorination in both side chains\ and in the preparation of compounds such as3!nitrobenzotrichloride where the electron!withdrawing group inhibits chlorination[ Thus\ car!boxylic acid groups in aromatic and heteroaromatic rings are converted into trichloromethyl groupsby treatment with phosphorus pentachloride in thionyl chloride ð66JHC770\ 67JHC782Ł\ or withphosphorus pentachloride alone ð78JCS"P0#172Ł[ This conversion can also be accomplished bytreating acids with chlorine in a mixture of phosphorus trichloride and phenylphosphonic dichlorideð72USP3308403Ł or phenyl dichlorophosphorane and phenylphosphonic dichloride ð78USP3722149Ł[Substituted benzal chlorides\ which can be prepared from the corresponding aldehydes ð67JOC3256Ł\can be chlorinated further to trichloromethyl compounds by treatment with isobutyl hypochloritein aqueous sodium hydroxide\ optionally in the presence of an alcohol\ and a phase transfer agentð67USP3987720Ł[ Substituted benzyl and benzal chlorides are also converted into the correspondingbenzotrichlorides when they are treated with tetrachloromethane or hexachloroethane and aqueoussodium hydroxide in the presence of a phase transfer catalyst "PTC# by a process which probablyinvolves nucleophilic attack on chlorine "Equation "020## ð75S113Ł[

CCl3

RR

CCl4 or CCl3CCl3

50% aqueous , NaOH, PTC, reflux(131)

Cl X

X = H; R = 2-NO2, 2-NO2, 3-MeX = Cl; R = 2-NO2, 2-NO2, 3-Me, 2-Me, 3-Me, 4-Me, 2-Me, 2-Cl, 4-Et

A similar range of compounds is made by treating appropriate dibenzyl sulphides with chlorineor sulfuryl chloride "Equation "021## ð71S840Ł^ or by chlorinating with sulfuryl chloride the productobtained from treating an aldehyde with a dithiol in the presence of acid "Scheme 11# ð75USP3464454Ł[Dichlorine monoxide can be used to chlorinate methyl groups in methylnitrobenzenes and othermethylbenzenes which have electron!withdrawing groups on the aromatic ring "Equation "022## ðB!71MI 590!91Ł[ While 3!nitrotoluene and highly deactivated compounds such as 1!chloro!3!nitro!\ 2\3!dinitro! and 2\4!dinitrotoluene are converted into the corresponding benzotrichlorides in very highyield\ 1!nitrotoluene is only dichlorinated by dichlorine monoxide to give the benzal chloride[ "NB[This compound could be chlorinated further by methods outlined above[# In the case of the othersubstituted toluenes with deactivating groups in the 3 position\ chlorination takes place exclusivelyin the methyl group with the exception of p!toluenesulfonic acid\ which undergoes chlorination onthe ring[

(132)Cl2 or SO2Cl2

CCl4, POCl3 or o-dichlorobenzeneCCl3

RR

S

R

2

R = 2-Mea, 3-Meb,c, 4-Mea, 2-Bra, 4-NO2d,e, 2,3-CH=CH–CH=CHa

aCl2/CCl4, bCl2, cSO2Cl2/CCl4, dCl2/POCl3, eCl2/o-dichlorobenzene

18Trichloromethyl

RCHO

RCCl3

RS

S ( )n

HS SH( )n

HCl in CHCl3

SO2Cl2

CCl4

Scheme 22

R = 3-Me, 4-NO2, 2-Cl, 4-MeO; n = 2 or 3

NO2

2 + 3Cl2OCCl4

NO2

CCl3

2 + 3H2O (133)

5[90[2[1[1 Transfer of the trichloromethyl group to an aromatic ring

Aromatic compounds can be trichloromethylated by reaction with tetrachloromethane in thepresence of excess Lewis acid\ which is most commonly aluminum trichloride "e[g[\ ð76JPR0020Ł#[Whilst the trichloromethyl compounds can be the main product\ diaryldichloromethanes are alsoproduced in signi_cant amounts "Equation "023##\ although it is claimed that the addition ofmordenite can reduce dimer formation ð81JAP93038032Ł[ The reaction is fairly general\ but there arecomplications when polymethyl aromatics are trichloromethylated[ Thus\ while m!xylene gives theexpected 1\3!dimethyltrichloromethylbenzene\ a Jacobson!type rearrangement occurs in the reactionwith p!xylene to give 1\3!dimethyltrichloromethylbenzene as the main product "o!xylene givesno trichloromethyl compounds but yields the dichloromethane\ "2\3!Me1C5H2#1CCl1# ð78CS70Ł[Similarly\ the trichloromethylation of mesitylene gives the expected product ð50JA3359Ł\ but duringthe trichloromethylation of pseudocumene ð78CS70Ł both the expected 1\3\4!trimethyltrichloro!methylbenzene and about 04) of the rearranged 1\3\5 isomer are produced "Scheme 12#[ Althoughmesitylene itself gives only the expected trichloromethylmesitylene\ 0\2\4!trimethylhalobenzenes givesigni_cant amounts of the rearranged product "Scheme 13^ in this scheme the products were isolatedas the corresponding methyl benzoates# ð69JOC2526Ł[ In the case of the tetramethylbenzenes "Scheme14#\ durene gives almost exclusively the rearranged product\ 1\2\3\4!tetramethyltrichloromethyl!benzene "a small amount of disproportionation took place under the conditions used#\ whereasisodurene gives predominantly 1\2\3\5!tetramethyltrichloromethylbenzene\ some of the 1\2\3\4 iso!mer and a trace of the 1\2\4\5 isomer ð50JA3359Ł[ It was suggested that rearranged products in thesereactions could arise by the trichloromethyl group attacking a ring carbon that is already substitutedfollowed by a 0\1!methyl migration and proton loss\ but rearrangements induced by acid\ HCl:AlCl2\are also possible[

ClCl

CCl3 +CCl4, AlCl3

(134)

CCl3

CCl3

mesitylene

pseudocumene

CCl4, AlCl3

CCl4, AlCl3

CCl4, AlCl3

100%

15%

85%

Scheme 23

29 Trihalides

X

CCl3

AlCl3, CCl4

X X

CCl3

Scheme 24

+

XHFClBr

100708893

030127

::::

CCl3

CCl3

durene

isodurene

CCl4, AlCl3

CCl4, AlCl3

CCl4, AlCl3

23%

2%

CCl3

Scheme 25

CCl4, AlCl3

73%

Highly chlorinated trichloromethyl and tri~uoromethyl aromatics are quite di.cult to prepare\but Castaner et al[ ð80JOC092Ł found that treatment of polychlorinated benzenes with aluminumtrichloride and ~uorotrichloromethane gives the tri~uoromethyl compound[ Treatment of this withmore aluminum trichloride in carbon disul_de yields the corresponding trichloromethyl compound[This reaction is reversed by treating the trichloromethyl compound with aluminum trichloride and~uorotrichloromethane[ Bis"trichloromethyl# and bis"tri~uoromethyl# compounds were also madeby these methods "Scheme 15#[

Cl Cl Cl

CF3 Cl3

CCl3F, AlCl3 AlCl3, CS2

CCl3F, AlCl3

Scheme 26

Trichloromethyl anions can be used to prepare trichloromethylated aromatics ð89TL5720\80JOM"308#246Ł[ In a one!pot reaction sequence\ a cyclopentadieneyliron!complexed arene is addedto a solution made from potassium t!butoxide and chloroform in THF at −67>C[ The mixture isallowed to warm to room temperature\ and the intermediate is demetallated in situ with iodine togive the trichloromethylarene in good yield "Scheme 16#[

Aromatic compounds that are susceptible to nucleophilic attack\ such as 0\2\4!trinitrobenzene\can be trichloromethylated by reaction with trichloromethyl anions generated by the decompositionof trichloroacetic acid in DMSO[ The _rst step is the formation of the Meisenheimer complex\which is then oxidized to give the trichloromethylated product "Scheme 17# ð72CC039\ 73JCS"P1#0128Ł[

20Tribromomethyl

R2

R1

FeCpPF6 R2

R1CCl3

R2

R1

FeCp

HCl3C

I2HCCl3, ButOK

–78 °C, THF

R1

MeMeMeHNO2HCl

R2

2-Me3-Me4-Me

p-TolSO24-MeBut

4-Clindanetetralin

benzosuberane

Scheme 27

Similarly\ hexachloroacetone can be used as the source of trichloromethyl anions[ The decompo!sition of hexachloroacetone in DMSO is slower than that of trichloroacetic acid\ but it is acceleratedby the addition of water[ It is believed that it is actually the hexachloroacetone hydrate thatdecomposes into the trichloromethyl anion\ and trichloroacetic acid which in turn decomposes togenerate a second trichloromethyl anion ð75JCS"P1#360Ł

O2N NO2

NO2

O2N NO2

NO2

O2N NO2

NO2

CCl3 CCl3

CCl3CO2H

DMSO

Scheme 28

–

5[90[3 TRIBROMOMETHYL DERIVATIVES*RBr2

Considerably less work has been carried out on making compounds bearing a tribromomethylgroup than on those bearing a trichloromethyl group[ With few exceptions\ the essentials of themethods for making tribromomethyl compounds are the same as those for making the trichloro!methyl analogues[

Thus\ tribromomethyl carbinols are produced when cyclohexanone is treated with tribromomethyllithium at −67>C in THF ð63JA2909Ł\ or when various 2!pyridyl ketones are reacted at −099>Cð77M0316Ł[

Corresponding to the decarboxylation of trichloroacetic acid and its sodium salt to give thetrichloromethyl anion is the decarboxylation of the analogous tribromo compounds[ The maindi}erence between the two systems is that the tribromo compounds are less stable[ Thus\ tribromo!methyl carbinols are obtained when sodium tribromoacetate decomposes in the presence of alde!hydes[ In a similar reaction\ anhydrides react to give tribromolactols or their tautomeric keto acidsð56JOC1055Ł[ Tribromomethyl carbinols are also obtained when\ in the presence of aldehydes\tribromoacetic acid decarboxylates in DMSO ð72CC172\ 73JCS"P1#0136Ł\ or a mixture of the acid andits sodium salt decarboxylates in DMF ð81TL2324Ł[

Again corresponding to the trichloromethyl case\ the reaction between tributyl"tribromo!methyl#stannane and an aldehyde gives a tribromomethyl carbinol[ The main di}erence betweenthe two reactions is that tribromomethylation is exothermic at room temperature whereas trichloro!methylation requires some heating ð64JOM"091#312Ł[

Finally\ tribromomethyl carbinols can be made by the reductive addition of tetrabromomethaneto aldehydes using a lead:aluminum bimetal system ð78JOC333Ł[

21 Trihalides

5[90[4 MIXED SYSTEMS WITH FLUORINE*RCF1Hal

Per~uoroalkyl iodides*CnF1n¦0I*are some of the most important intermediates in the prep!aration of compounds which bear the per~uoroalkyl group "e[g[\ ð73JFC"14#58\ 77MI 590!90Ł#[ Somemethods for the preparation of these compounds have been described previously "see Sections5[90[0[0 and 5[90[0[1[1#\ but there are others which need to be noted[ Most of these methods take aper~uorocarboxylic acid as their starting point[ For example\ the thermal decomposition of the acidin the presence of iodine ð42USP1536822Ł\ the decomposition of per~uoroacyl chlorides in the presenceof potassium iodide at 199>C ð47JOC1905Ł\ the decomposition of per~uoroacyl anhydrides in thepresence of iodine at 249Ð399>C ð46BRP646782Ł and the thermal decomposition of dry metal salts inthe presence of iodine all give per~uoroalkyl iodides[ Sodium\ potassium\ barium\ mercury and leadsalts have all been used in this last reaction\ but it is silver salts which give the best yields ð40JCS473\41JA737\ 41JA738Ł[ This is known as the Hunsdiecker reaction\ and it can also be used to obtain{dihalides| from the corresponding diacid salts\ although lactone formation can be a problemð41JA737\ 41JA0863Ł[ More recently\ it has been shown that treatment of sodium and potassium saltsof per~uorocarboxylic acids with iodine in re~uxing DMF gives per~uoroalkyl iodides in high yieldð56JOC722Ł[

One compound in this class which has attracted a lot of interest of late is per~uorooctyl bromide"PFOB# because of its potential use as a contrast agent for diagnostic imaging[ The telomerizationreaction between bromopenta~uoroethane and tetra~uoroethylene does not a}ord a convenientroute to PFOB because the propagation step is so much faster than chain transfer\ and a mixtureof high telomers is obtained[ Most of the practical routes for the manufacture of PFOB start fromper~uorooctyl iodide\ which of course is manufactured on a substantial scale\ and replace the iodineby bromine[ For example\ iodides can be treated with bromine in the vapour phase at 299Ð249>Cð80EUP349473\ 81EUP404147Ł\ or with ultraviolet irradiation for 09 h ð73MI 590!90Ł[ Also\ PFOB canbe made by re~uxing per~uorooctyl iodide with tetraalkylphosphonium bromide ð81GEP3914116Ł\or with sodium bromide ð80GEP2826456Ł in DMF "a certain amount of reduction to the monohydrocompound occurs here#\ and by heating with metal "Cs\ Mn"II#\ Fe"II# Fe"III# or Co"II## bromidesto 299>C in an autoclave ð80EUP350452Ł[

5[90[5 MIXED HALOFORMS*CHXY1 AND CHXYZ

Most methods for the preparation of mixed haloforms take the simple haloforms and replace oneor two of the original halogens by others[ Trichloromethane "chloroform# is ~uorinated on anindustrial scale in the liquid phase using Swarts| catalyst or in the vapour phase using chromia!based catalysts with hydrogen ~uoride as the ~uorinating agent "see also Section 5[90[0[2#[ Thecompound of greatest interest to the manufacturer is chlorodi~uoromethane\ since it is used in themanufacture of tetra~uoroethene\ but dichloro~uoromethane can also be made by this method[Similarly\ tribromomethane "bromoform# can be ~uorinated using antimony tri~uoride and bromineð54BRP0903141Ł\ or a ~uoride!type ion exchange resin ð51NKZ825Ł\ to give dibromo~uoromethane"Equation "024##[

CHBr3 CHBr2Fi, ii

(135)

i, SbF3, Br2, reflux; ii, amberlite IRA-400 (F type), 80 °C

Chloroform\ bromoform and iodoform can all be treated with an alkali metal halide and a basein the presence of a phase transfer agent to give mixed haloforms "e[g[\ Equations "025#Ð"039##ð78LA076\ 76TL1658Ł\ but satisfactory yields are not always obtained[ A single iodine in iodoform canbe replaced by bromine simply by stirring a mixture of iodoform and bromine in tetrachloromethanefor some 04 h "Equation "030## ð71CB2783Ł[

CHCl3 CHBrCl2NaBr, NaOH, PTC

(136)

CHCl3 CHCl2I + CHClI2NaI, NaOH, PTC

(137)

22Mixed Haloforms

CHBr3 CHBr2ClNaCl, NaOH, PTC

(138)

CHBr3 CHBr2INaI, NaOH, PTC

(139)

CHI3 CHClI2 + CHCl2INaCl, NaOH, PTC

(140)

CHI3 CHBrI2

Br2, CCl4 (141)

Dibromochloromethane reacts with sodium iodide and sodium methoxide in methanol to givebromochloroiodomethane "Equation "031## ð47JA3171Ł\ and with mercuric ~uoride to give bromo!chloro~uoromethane "Equation "032## ð45JA368\ 74JA5882Ł[ Bromochloro~uoromethane having highoptical purity has been made by pyrolysing the optically pure strychnine salt of bromochloro!~uoroacetic acid ð78JA7409Ł[

CHBr2Cl CHBrClINaI, NaOH, MeONa

(142)

CHBr2Cl CHBrClFHgF2

(143)

The thermal decarboxylation of silver salts of halogenated acetic acids in the presence of a halogen"the Hunsdiecker reaction*see Section 5[90[4# has been used to make the haloforms CHCl1F\CHClF1\ CHClBrF\ CHClFI\ CHBr1F\ CHBrFI\ CHFI1\ CHBrF1 and CHF1I "e[g[\ Equations "033#and "034## ð41JCS3148Ł[

CHF2CO2Ag + I2 CHF2I (144)

CHClFCO2Ag + Br2 CHClBrF (145)

All Rights Reserved# Copyright 1995, Elsevier Ltd. Comprehensive Organic Functional Group Transformations

6.02Functions Containing Halogensand Any Other ElementsGRAHAM B. JONES and JUDE E. MATTHEWSClemson University, SC, USA

5[91[0 FUNCTIONS CONTAINING HALOGEN AND A CHALCOGEN 25

5[91[0[0 Haloèn and Oxyèn Derivatives "R0CHal1OR1 and R0CHal"OR1#1# 255[91[0[0[0 Tetracoordinated carbon atoms with two identical haloèn and one oxyèn function

attached "R0CHal1OR1# 255[91[0[0[1 Tetracoordinated carbon atoms bearin` mixed haloèns and one oxyèn function

"R0CHal1OR1# 325[91[0[0[2 Tetracoordinated carbon atoms bearin` one haloèn and two oxyèn functions

"R0CHal"OR#11# 32

5[91[0[1 Haloèn and Sulfur Derivatives "R0CHal1SR1 and R0CHal"SR1#1# 335[91[0[1[0 Tetracoordinated carbon atoms with two identical haloèn and one sulfur function

attached "R0CHal1SR1# 335[91[0[1[1 Tetracoordinated carbon atoms bearin` mixed haloèns and one sulfur function

"R0CHal1SR1# 365[91[0[1[2 Tetracoordinated carbon atoms bearin` one haloèn and two sulfur functions

"R0CHal"SR1#1# 375[91[0[2 Haloèn and Se or Te Derivatives "R0CHal1SeR1 or R0CHal1TeR1# 38

5[91[0[2[0 Tetracoordinated carbon atoms bearin` two haloèns and one selenium function"R0CHal1SeR1# 38

5[91[0[2[1 Tetracoordinated carbon atoms bearin` two haloèn and one tellurium function"R0CHal1TeR1# 38

5[91[0[3 Haloèn and Mixed Chalcoèn Derivatives "R0CHal"OR1#"SR2## 49

5[91[1 FUNCTIONS CONTAINING HALOGEN AND A GROUP 04 ELEMENT ANDPOSSIBLY A CHALCOGEN 49

5[91[1[0 Haloèn and Nitroèn Derivatives] General Considerations 495[91[1[0[0 Tetracoordinate carbon atoms bearin` two haloèns and one nitroèn function 405[91[1[0[1 Tetracoordinate carbon atoms bearin` one haloèn and two nitroèn functions 445[91[1[0[2 Tetracoordinate carbon atoms bearin` one haloèn\ one nitroèn and one oxyèn function 465[91[1[0[3 Tetracoordinate carbon atoms bearin` one haloèn\ one nitroèn and one sulfur function 46

5[91[1[1 Haloèn and Phosphorus Derivatives 475[91[1[1[0 Tetracoordinate carbon atoms bearin` two haloèn and one phosphorus function and

one haloèn and two phosphorus functions 475[91[1[2 Haloèn and Arsenic Derivatives 59

5[91[1[2[0 Tetracoordinate carbon atoms bearin` two haloèns and one arsenic function 59

5[91[2 FUNCTIONS CONTAINING HALOGEN AND A METALLOID AND POSSIBLYA CHALCOGEN AND:OR GROUP 04 ELEMENT 59

5[91[2[0 Haloèn and Silicon Derivatives 595[91[2[1 Haloèn and Boron Derivatives 505[91[2[2 Haloèn and Germanium Derivatives 51

5[91[3 FUNCTIONS CONTAINING HALOGEN AND A METAL AND POSSIBLY A GROUP04 ELEMENT\ A CHALCOGEN OR A METALLOID 51

5[91[3[0 Haloèn and Lithium Derivatives 515[91[3[1 Haloèn and Ma`nesium Derivatives 525[91[3[2 Haloèn and Copper Derivatives 52

24

25 Haloèns and any other Elements

5[91[3[3 Haloèn and Silver Derivatives 525[91[3[4 Haloèn and Zinc Derivatives 535[91[3[5 Haloèn and Cadmium Derivatives 535[91[3[6 Haloèn and Mercury Derivatives 535[91[3[7 Haloèn and Tin Derivatives 545[91[3[8 Haloèn and Lead Derivatives 54

5[91[0 FUNCTIONS CONTAINING HALOGEN AND A CHALCOGEN

A general review on ortho!ester derivatives covering the literature up to 0873 has been publishedð74HOU"E4#Ł and provides a broad overview of several categories of haloalkyl systems relevant tothis chapter[

5[91[0[0 Halogen and Oxygen Derivatives "R0CHal1OR1 and R0CHal"OR1#1#

5[91[0[0[0 Tetracoordinated carbon atoms with two identical halogen and one oxygen functionattached "R0CHal1OR1#

"i# From ethers

Direct halogenation of ethers has proved a versatile technique for the synthesis of a variety ofperhalogenated compounds of this class[ Novel per~uorinated ethers have been obtained by direct~uorination of low molecular weight ethers with product ratios a function of the ~ow rate of~uorine and carrier gas "usually helium# "Scheme 0# ð62JOC2506Ł[ The method has also been appliedsuccessfully to the preparation of per~uorinated polymers\ although in these cases the mixturesrequired heating up to 009>C for e.cient conversion ð66CC148\ 70JCS"P0#0210Ł[ Electrochemical~uorination has also been investigated\ but it was found that\ under the optimum conditions used\primary alcohols were converted into cyclic per~uorinated ethers in only moderate yield "Equation"0## ð65BCJ0777Ł[ The electrochemical ~uorination of ethylene glycol ethers has also been reported\yielding complex mixtures of linear and cyclic per~uorinated compounds ð63ZOR1920Ł[

MeO

OMe

F3CO

OCF3

F F

F F

MeO

OO

Me F3CO

O

F F

F F

OCF3

F

F F

F

20 ml/min He, 0.5 ml/min F2, –78 °C, 12 h

21%

20 ml/min He, 0.5 ml/min F2, –40 °C

16%

Scheme 1

OH

O

FF

CF3

F

FF

F

F

HF, 3.5 A/1; 5 °C, 0–10 V

18%(1)

Photochlorination of mixed halogenated ethers has been used in the synthesis of a number ofanaesthetic agents "Scheme 1#[ Yields of the chlorinated systems are moderate to good\ reactivitybeing a function of carbon substitution patterns\ with monochlorinated carbon atoms being morereactive than the corresponding ~uoro!substituted carbons as expected ð41JA1181\ 60JMC406\60JMC482Ł[ Fluorination via direct substitution of chloro ethers has been accomplished using eitherHF or HF in the presence of SbF2 "Equation "1##[ Selectivity can be achieved by controlling HFintroduction\ monitoring the progress of the substitution reaction by the HCl liberated ð60JMC482Ł[Halogenation of heterocycles is a well!studied route to compounds of this class with trisubstituted

26Halo`en and a Chalco`en

carbon atoms[ Electrochemical ~uorination of a range of oxanes gave the corresponding per!~uorinated systems in moderate yield "Equation "2## ð68JFC"02#408\ 68JFC"04#242Ł[

Cl OF

F

FFCl O

F

F

FFCl

ClOF3C ClOF3C

Cl

FOF3C

FCl Cl

FOF3C

FCl

ClOF3C

ClCl2, hν

60%Me

OF3C

Cl2, hν

75%

Scheme 2

Cl2, hν

80%

Cl2, hν

80%

FOF3C

FCF3

ClOF3C

ClCF3 HF, SbCl5, 0 °C, 12 min

or SbF3, SbCl5, 53 °C, 3 h62%

(2)

O R O Rf

F

electrochemical fluorination, HF

5.0–6.2 V, 3.5 A/dm2, 7 h

R = Me, 28%; Et, 26%; Prn, 30%; Pri, 23%; Bun, 30%; Amn, 23%

(3)

Direct ~uorination of dioxane using elemental ~uorine is reported to give the per~uorinatedsystem in moderate yield "Scheme 2# ð64JOC2160Ł\ whereas treatment with a mixture of sulfurtetra~uoride and hydrogen ~uoride gave the 1\1\2!tri~uorodioxane in high yield "Scheme 2#ð72JFC"11#094Ł[ The same product is also reported using the potassium salt of cobalt tetra~uorideð60T3422Ł[ Finally\ ~uorination of 3!methylmorpholine using cobalt tri~uoride is reported to givethe di~uoromethyl derivative shown in moderate yield "Scheme 2# ð67T086Ł[

O

O

O

O

FSF4, 185 °C, 8 h; S2Cl2

89%

O

O

O

O F

F

F

KCoF4, 220 °C

65%

N NMe

F

F

FCoF3, 100 °C

31%

Scheme 3

"ii# From mixed trihalomethanes

Chlorodi~uoromethane has been used extensively as a source of di~uoromethylene\ which can beintercepted by alkoxide nucleophiles to give alkoxydi~uoromethane adducts[ The conditions used


are similar to those employed in the ReimerÐTiemann reaction\ and give good yields of productdi~uoro ethers "Equation "3## ð47JA2991\ 59JOC1998Ł[ A phase transfer method has also been used togenerate di~uorocarbene from chlorodi~uoromethane ð77JFC"30#136Ł[

R OH O

F

F

R i, NaOH, H2O, dioxane, 70 °Cii, CHFCl2

R = Ph, 65%; 4-MeC6H4, 66%; 4-MeOC6H4, 53%; 2,4-Me2C6H3, 56%; 2,4-Cl2C6H3, 44%; 2-naphthyl, 66%; Pri, 60%

(4)

The range of functionality tolerated by the reaction includes substituted primary and secondaryalkyl halides\ which provides access to heavily functionalized systems "Scheme 3# ð65CB1240Ł[Trihalomethylmercury compounds have also been used to deliver the dihalomethyl moiety toalcohols and carboxyl groups ð53JA1850\ 63JOM"56#230Ł[ Phenyl"bromodichloromethyl#mercury thusadds to carboxylic acids to yield the dichloromethyl esters shown "Scheme 4#\ and with butanol togive the dichloro ether shown in high yield\ producing phenylmercuric bromide as by!product inboth cases[ Di~uorocarbene has also been generated from FSO1CF1CO1H\ and it inserts intoalcohols in the presence of CuI ð78JFC"33#322Ł[

O F

Cl O

F

Cl

F Cl

F

OH

Cl

ClHClCF2

97%

Cl

OH

Cl

O

ClCl

O

F

FFF

HClCF2

98%

Scheme 4

Cl

O

O

ClR

Cl

PhHgCCl2Br + RCO2Hbenzene, 60 °C, 45 min

+ PhHgBr

R = Ph, 86%; Me, 92%; ClCH2, 86%; But, 81%

OBu

ClClPhHgCCl2Br + BuOH

PhEt, 80 °C, 30 min

85%+ PhHgBr

Scheme 5

"iii# From dihalo ethers

Treatment of dichloro ethers and bromochloro ethers with antimony tri~uoride results in halogensubstitution to yield the corresponding di~uoro ether "Scheme 5# ð52AFC"2#070\ 69ZOR033\ 61JMC593\61JMC595Ł[ Alternatively\ anhydrous hydrogen ~uoride can be used in the presence of antimonypenta~uoride giving high yields of the di~uoro adducts "Equation "4## ð61JMC593Ł[ Treatment of


cyclic per~uorinated ethers with aluminum trichloride is reported to give the corresponding a\a\a?!trichloro ether in good yield "Equation "5## ð67JFC"01#248Ł[

CF3OCl

ClCl

CF3OF

ClF

F OF

Cl

FFF

Cl OF

Cl

FFCl

MeO

Br

FBr

BrFMe

OBr

FBr

FF

O

ClCl

ClCl

CF3

C F3

O

FF

FF

CF3

CF3

MeOCl3C

F FMe

OCl3C

Cl Cl

SbF3, 60 °C

75%

SbF3, 60 °C

70%

SbF3, 117 °C

51%

SbF3, ∆

67%

SbF3, ∆

84%

Scheme 6

F OF

F

FFF

Cl OF

F

FFCl

(5)HF, SbCl3, 0 °C

80%

AlCl3, 143 °C, 19 min

53%OF3C O

Cl

F3C Cl

Cl(6)F F

"iv# From carbonyl derivatives

Electrochemical ~uorination of acyl chlorides and esters has been used to prepare compounds ofthis class[ The process gives moderate yields of cyclic per~uorinated ethers\ but often results information of mixtures "Scheme 6# ð67JFC"01#0\ 72JFC"12#012Ł[

Sulfur tetra~uoride has been shown to be e}ective for the conversion of the carbonyl group to adi~uoromethylene group[ Thus\ treatment of a variety of anhydrides\ esters\ and formate esters withsulfur tetra~uoride yields the corresponding di~uoromethylene systems\ often in high yield "Scheme7# ð59JA432\ 53JOC0\ 69ZOR033\ 64ZOR0561\ 65ZOR0176\ 65ZOR0687\ 72JFC"11#196Ł[ Exposure of aryl!ortho!diacid systems to the same conditions results in ring formation in addition to partial per~uorination"Scheme 8# ð69ZOR1387Ł[

Phosphorus pentachloride has been shown to react with a variety of formate esters to yield thecorresponding a\a!dichloro ethers "Equation "6## ð52CB0276\ 56OS"36#36\ 60RTC445Ł[ The analogousaddition reactions are also applicable to oxalates and other carboxylic esters\ which constitute high!yielding routes to dichloro ethers\ trichloro ethers\ and dichloroacetates "Scheme 09# ð40JA4057\45M212\ 64S416Ł[ a!Chlorination of a!chloro!a!alkoxyacyl chlorides has also been employed\ givingthe corresponding dichloroalkoxyacyl chloride in good yield "Scheme 09# ð48CB2069Ł[


OF3C

C3F7

Cl

O

OC2F5

C4H9

OMe

O

HF/3.5 A/dm2, 5 °C, 6.4 V, He 100 ml/min

20%

Scheme 7

HF/3.5 A/dm2, 5 °C, 6.4 V, He 100 ml/min

19%O

CF3OMe

O

F

HF/3.5 A/dm2, 5 °C, 6.4 V, He 100 ml/min

21%

F

FF

O

Cl Cl

OO O

Cl Cl

F

F F

FSF4, 300 °C, 10 h

46%

X

O CF3

OX

O CF3

F F

SF4, HF, ∆

OCOCF3

OCOCF3

OCOCF3

OCOCF3

OC2F5

OC2F5

OC2F5

OC2F5

SF4, HF, ∆

79%

Scheme 8

X = H, 61%; 4-NO2, 69%; 3-NO2, 83%; 2-Cl, 71%; 4-Cl, 74%; 4-F, 69%; 3-Me, 63%; 4-Me, 46%; 2-MeO, 36%

SF4, ∆

CO2H

CO2H

CO2H

CO2H

SF4, ∆

76%

CF3

CF3

O

O

FF

CF3

CF3

O

FF

FF

Scheme 9

RO Cl

Cl

RO

O PCl5, ∆+ POCl3

R = Me, 84%; But, 68%; Ph, 85%

(7)

Another versatile route is o}ered using a\a!dichloromethyl methyl ether as a transfer agent\ inthe presence of mercuric chloride[ A variety of aryl formate esters have been converted to thecorresponding dichloromethyl ethers using this very high!yielding method "Equation "7##ð60RTC445Ł[


O

OPh OPh

Cl Cl

O

ORO

R ORO

R

Cl

Cl Cl

O

OEtO

Et OEtO

Et

O

Cl Cl

O

ClEtO

O

Cl

ClEtO

PCl5, 80 °C

>50%

O

PCl5, 85–90 °C, 12 h

Cl

R = Me, 75%; Et, 85%

Cl

PCl5, 110 °C, 15 h

65%

Cl2, 150 °C

70%

Scheme 10

X

O Cl

ClX

O

O

MeOCHCl2, HgCl2

X = H, 85%; 2-Me, 94%; 3-Me, 90%; 4-Me, 90%; 3-Cl, 90%; 4-NO2, 86%; 3-HCl2CO, 90%

(8)

"v# From haloalkoxyalkenes

Chlorination of chloroalkoxyalkenes has been used successfully to give the correspondingdichloroalkoxyalkanes in good yield "Scheme 00#[ Typical conditions involve exposure of the alkeneto a stream of chlorine gas or dry hydrogen chloride "generated in situ# at −4>C followed bydistillation of the product ð46RTC858\ 47CB795Ł[

OEt

Cl

Cl

OEt

Cl

OEt

Cl

Cl

OEt

ClCl Cl

OEt

Cl

Cl

OEt

Cl

dry Cl2, –5 °C

74%EtO EtO

Cl Cl

Cl

dry HCl, 0 °C

88%

dry HCl, –5 °C

73%

Scheme 11

"vi# From haloalkenes

The addition of primary alcohols to halogenated alkenes proceeds rapidly\ giving dihaloalkoxy!alkanes in high yield[ The reactions are often catalyzed by trace amounts of the correspondingmetal alkoxide^ this is often required for addition of less reactive secondary and tertiary alcohols\which usually give mixtures of products "Scheme 01# ð59JOC882\ 54AFC"3#49\ 63BSF1961Ł[ Electron!withdrawing substituents on the alkene also accelerate the reaction^ thus\ methyl tri~uoroacrylate


reacts faster than methyl acrylate ð62CCC55\ 75ZOR0723Ł[ Addition of oximes has also beenaccomplished\ merely requiring more elevated temperatures "Scheme 01# ð62CCC55Ł[ Addition ofalkyl and trihaloalkyl hypohalites to haloalkenes is another useful route to this class[ A variety ofprimary and tertiary alkyl hypohalites add cleanly at low temperature "Scheme 01# to give high yieldsof the adducts ð69JOC2629\ 64JA02\ 64JFC"4#14Ł[ Bis"tri~uoromethyl#trioxide has also been employed forthis type of addition reaction\ which is applicable both to acyclic and cyclic alkenes "Scheme 01#ð63JOC0187Ł[ Per~uorinated alkenes are reported to react with sulfur trioxide to give cyclic per~uoro!1!b!sulfones in excellent yield ð75ZOR0731Ł[ Per~uoroalkenes also react with halogen mono~uoro!sulfates to yield both 1!haloalkyl~uoroalkyl ~uorosulfates and vicinal bis"halosulfonyloxy#~uoroalkanes ð74IZV548Ł[

F

FF

F F

FF

F

OBun

F

FF

Cl

Cl

O

F

F

FOH

F

FBr

Br

BrO

Et

Br

F F

F

F

FF

EtCO2

EtCO2 ON

F F FN

OH

F

BunOH, 10% Na, 0–38%

81%

F

FCl

OCF3

F F

, 5% Na, THF, –10 °C

F

FF

F3C

F3CO CF3

CF3CF3FF

FF

FO CF3

CF3

CF3

EtOH, 10% Na, –10 °C–>16 °C

79%

, DME, 10% Na, 25 °C

ClOMe, –80 °C

96%

92%

75%

, –62 °C–>25 °C

95%

F

F

O2CF3

OCF3

CF3OO2CF3, 67 °C, 8 h

80%

Scheme 12

Epoxidation of ~uoroalkenes is a convenient route to a\a!di~urorooxiranes[ High yields areattainable at low temperature using moderate to high strength hydrogen peroxide "Equation "8##ð55JOC1201\ 69JOC1943\ 61MI 591!90\ 62ZOR1902Ł[

F

F

F

C4F9

O

C4F9

F F

F60% H2O2, MeOH, –20 °C, 8 h

82%(9)

a\a!Dichlorooxiranes have been used by Corey in the enantioselective synthesis of azido andamino acids "Scheme 02#[ The oxiranes\ generated in situ from trichloromethyl carbinols\ areimmediately ring!opened by the SN1 attack of aqueous azide\ subsequent oxidation giving a!azidoacids in high yield ð81JA0895Ł[


R CCl3

H OH O

ClCl

H

R R CO2H

N3 HNaOH, NaN3

then KH2PO4

R = n-C5H11, 89%; C6H5(CH2)2, 91%; c-C6H11, 89%; But, 80%

Scheme 13

5[91[0[0[1 Tetracoordinated carbon atoms bearing mixed halogens and one oxygen function"R0CHal1OR1#

Selective mono~uorination of dichloro ethers has been used to prepare chloro~uoro ethers inmoderate to good yield "Scheme 03# ð60JMC482\ 61JMC593\ 64JFC"5#26Ł[ Another useful strategy isaddition of tri~uoromethyl hypochlorite to mixed 0\0!dihaloalkenes giving the dihalo ethers inexcellent yield "Scheme 03# ð69JOC2629\ 61JMC595Ł[ The ester BrCF"OPh#CO1Et has been preparedby bromination of ethyl~uoro"phenoxy#acetate ð75JOC844Ł[

Cl OF

Cl F F

FF

Cl OF

F F F

FF

F3CO

FF Cl

FCl

F

F F

Cl

anhydrous HF, SbCl5 (cat.), 0 °C

80%

ClOCF3, –80 °C

90%

Scheme 14

5[91[0[0[2 Tetracoordinated carbon atoms bearing one halogen and two oxygen functions"R0CHal"OR#1

1#

Numerous examples of compounds of this class exist\ as the corresponding carbenium ion halidesalt\ a consequence of stabilizing in~uence of the alkoxy functions ð61CRV246\ 71S0\ 74HOU"E4#Ł[ Thefollowing examples described are clear!cut cases where the chemistry is best described by the covalentspecies[

"i# From 0\2!dioxolanes

Direct formation of 1!~uoro!1!tri~uoromethyl!0\2!dioxolanes has been accomplished by treatingaryl ortho!bis"tri~uoroacetic# esters with a mixture of sulfur tetra~uoride and hydrogen ~uorideð65ZOR0176Ł[ Formation of 1!chloro!0\2!dioxolanes has been achieved using a variety of protocolsð56LA"696#24Ł[ Chlorination of derived ortho!esters with phosphorus pentachloride at elevated tem!peratures is a high!yielding process\ as is direct chlorination of unsubstituted 0\2!dioxolanes "Scheme04# ð50CB433\ 55CB1514\ 56LA"696#24\ 57LA"619#035Ł[ A related procedure used substitutive chlorinationof a 1!acetoxy!0\2!dioxolane using dichloromethyl ether ð58TL4992Ł[ Alternatively\ displacement ofchloride from 1\1!dichloro!0\2!dioxolanes has been used ð55CB1514Ł[

"ii# From ortho!formates

Decomposition of vinyl ortho!formates is a versatile route to dialkoxymethyl halides[ Treatmentof dialkoxy vinyl ortho!formates with either hydrogen chloride or hydrogen bromide results in


O

OCl

Cl

ClO

OCl

Cl

O

O R1

OR2 O

O R1

Cl

SOCl2, 80 °C

92%

PCl5, 110 °C

R1 = Ph, R2 = Me, 88%R1 = CO2Et, R2 = Et, 53%R1 = H, R2 = Et, 87%

Scheme 15

liberation of the dialkoxyhalomethane "Scheme 05# ð60RTC0012Ł[ Alternatively\ substitution oftriaryl ortho!formates with acetyl chloride has been reported to give good yields of the chloro!diaryloxymethane ð51CB0748Ł[

OR

RO O

OR

RO X

OPh

PhO OPh

OPh

PhO Cl

HCl or HBr, Et2O, 25 °C, 15 min

R = CH=CH2, X = Cl, 50%R = Ph, X = Cl, 60%R = Ph, X = Br, 50%R = p-Tol, X = Cl, 65%R = C(Me)=CH2, X = Cl, 90%

MeCOCl

81%

Scheme 16

5[91[0[1 Halogen and Sulfur Derivatives "R0CHal1SR1 and R0CHal"SR1#1#

5[91[0[1[0 Tetracoordinated carbon atoms with two identical halogen and one sulfur function attached"R0CHal1SR1#

"i# From sul_des

a!Chlorination of sul_des is a popular route to these compounds\ and a variety of di}erentprotocols have proved e}ective including photochemical chlorination and use of thionyl chloride"Scheme 06# ð41JA2483\ 42LA"470#022\ 47LA"505#0\ 48LA"510#7\ 54JOC3900Ł[ The ester MeSCH1CO1Me hasbeen converted into the corresponding a\a!dichloro ester using thionyl chloride and into the dibromoester by reaction with bromine ð70AG"E#474Ł[

Cl

S ClMeMe

SMe

Cl

S ClMe

S ClMe

SOCl2, 0 °C, 1.5 h then 95 °C, 4 h

77%

Cl2, CCl4, –20 °C

57%

Scheme 17


"ii# From iodo~uoroalkanes

The photochemical reaction of ~uoroiodo alkanes with both methyl sul_de and dimethyl disul_dehas been investigated extensively\ and the radical addition process was found to give good yields ofthe corresponding di~uoro sul_des "Scheme 07#\ the only drawback being the sluggishness of thereaction ð61JCS"P0#044\ 61JCS"P0#048\ 61JCS"P0#0495\ 61JCS"P0#1327Ł[ Metallation of terminal iodo~uoro!alkanes with methyllithium at −67>C\ followed by addition of sulfur dioxide\ results in formationof a lithium di~uoroalkylsul_nate by attack of the intermediate organolithium species ð78S352Ł[

F3CS

Me

F F

F FF3C

IF F

F F

SS

Me

F F

F FF

FI F

F I

MeSSMe, UV, 21 d

93%

MeMeSSMe, UV, 30 d

48%

Scheme 18

"iii# From a\a!dichloroalkyl sul_des

Dichloroalkyl sul_des react smoothly with antimony tri~uoride in the presence of catalyticquantities of antimony penta~uoride to yield the corresponding di~uoro sul_des "Scheme 08#ð41JA2483\ 54JOC3900Ł[ The substitutions are regioselective for the carbons alpha to the sulfur centeras shown by control reactions[

Scheme 19

MeS

BrF F

F

MeS

BrCl Cl

F

SbF3, SbF5 (cat.)

46%

Cl S Cl

ClCl

Cl

F S F

FF

F

SbF3, SbF5 (cat.)

75%

"iv# From chlorodi~uoromethane

Substitution of the chloro group of this haloform with thiols has been achieved using a variety ofconditions\ typically involving addition of a sodium thiolate followed by thermolysis "Scheme 19#ð46JA4382\ 68JOC0697\ 74S386Ł[ Some debate exists concerning the mechanism of the substitution\which appears to have both a carbene and SN1 type character[ A phase!transfer method\ whichundoubtedly involves di~uorocarbene\ has been described for preparation of sul_des ArSCHF1

from aromatic thiols ð77JFC"30#136Ł[

Cl F

F

PhS F

F

Na, MeOH then PhSH, 7 h

63%

Ph S F

F

Cl F

F

PhCH2SH, NaOH 50%, DMF, 65 °C

75%

Scheme 20


"v# From thioformates

Thioformates react cleanly with phosphorus pentachloride in carbon tetrachloride to yield thecorresponding a\a!dichloromethyl sul_des in high yield "Scheme 10#[ An alternative but slightly lesse.cient route to such compounds is via halomethylene transfer from dichloromethyl methyl ether\catalyzed by mercuric chloride ð61RTC238Ł[

PCl5, CCl4, –40 °C–>25 °C

76–87%R

S Cl

Cl

RS

O+ POCl3

RS Cl

ClMeOCCl2, HgCl2, reflux 4 h

75–93%R

S

O+ MeOCHO

Scheme 21

"vi# From alkenes

"a# Vinyl sul_des[ Chlorination of 0!chlorovinyl sul_des has been used to generatebis"alkylthio#tetrachloroethanes "Scheme 11#[ In this example the alkene is readily available viathiolate!induced substitution and elimination from the corresponding hexachloroethane ð47CB795Ł[

Cl3C CCl3

Cl

Cl

SEt

Cl

Cl

EtS

SEt

ClCl

EtSNaSEt Cl2

52%

Scheme 22

"b# 0\0!Dihaloalkenes[ Addition of thiols and disul_des to halogenated alkenes proceeds rapidlywhen they are subjected to either ultraviolet or x!ray radiation to give the corresponding additionproducts "Scheme 12#[ As expected\ addition of thiolates proceeds without photolytic conditions\but the reaction rates are heavily dependent on the nature of the haloalkene substitutents[ Mixedchloro! and bromo~uoroalkenes are far more reactive than tetra~uoroethylene\ which requiresforcing conditions ð59JA4005\ 50JA739\ 54JOC3900\ 55BCJ1080\ 61JCS"P0#23\ 63JFC"3#096\ 65JCS"P0#0067Ł[ Free!radical addition of tri~uoromethanesulfonyl chloride to haloalkenes under UV irradiation has beenemployed and gives moderate yields of the tri~uoromethylsul_de adducts "Scheme 12# ð51JA2037Ł[Thermolysis of tetra~uoroethylene with elemental sulfur is reported to produce _ve!\ and six!membered cyclic sul_des bearing a\a!di~uoromethyl groups in yields ranging from 09) to 59)ð51JOC2884Ł[ Addition of thiols to di~uoroalkenes catalyzed by Triton B is also reported to producea\a!di~uoroalkyl sul_des in high yield ð49JA2531Ł[ Activated haloalkenes\ including penta~uoro!propene!1!sulfonyl ~uoride\ undergo rapid addition of alkyl hydrosul_des\ yielding 0!alkylthio!1H!penta~uoropropane!1!sulfonyl ~uorides "Scheme 12# ð75ZOR0723Ł[

"vii# From carbon disul_de

Treatment of carbon disul_de with elemental ~uorine at −019>C is reported to yield octa~uoro!ethyl methyl sul_de in 59) yield ð66IC1863Ł[

"viii# From a!~uoroalkyl sulfoxides

The reaction of the sulfoxide of 3!MeOC5H3SOCH1F with "diethylamino#sulfur tri~uoride givesthe di~uorosul_de 3!MeOC5H3SCHF1 "57)# by a Pummerer!type reaction ð89JOC3646Ł[ The sul_de


F

F Cl

Cl

F

F

RSCl

Cl

RSH, x-rays, 3–4 weeks, 25 °C

R = Me, 71%; Et, 61%; Pri, 74%

F

F F

OMeF3C

SO

Me

F

FF

CF3SH, UV irradiation 15 min

71%

F

F F

ClMe

SCl

FF

FMeSH, 4M NaOMe

90%

F

F F

FS

F

FPh

F FPhSH, dioxane, 60–80 °C

91%

F

F F

R

SF

ClCF3

F F

R

ClSCF3, hν, 2 h (R = H)

R = H, 50%; CF3, 63%

F

F CF3

SO2FC4H9

SSO2F

FF

CF3C4H9SH, Et2O, –60 °C

66%

Scheme 23

can be oxidized to the corresponding sulfoxide and sulfone[ The reaction is\ however\ unsuccessfulwith PhSOCH1F[

5[91[0[1[1 Tetracoordinated carbon atoms bearing mixed halogens and one sulfur function"R0CHal1SR1#

Thiolate additions to mixed chloro~uoroalkenes under both radical and ionic conditions havebeen employed to synthesize mixed dihalo sul_des of this class "see Section 5[91[0[1[0#[ Typicalconditions parallel those for identically substituted haloalkenes\ and product yields are comparable"Scheme 13# ð48LA"510#7\ 51JA2037\ 55BCJ1080\ 63JFC"3#096\ 65JCS"P0#0067Ł[ Alternatively\ treatment ofdichloro sul_des with antimony tri~uoride results in monosubstitution of chlorine\ giving the mixed"chloro~uoro#sul_de in good yield "Scheme 13# ð48LA"510#7Ł[ The esters BrCF"SR#CO1Et "R�Etand Ph# have been prepared by NBS bromination of the corresponding "ethylthio#~uoroacetate or~uoro"phenylthio#acetate ð75JOC844Ł[

SF

FMe

F

Cl

ClF

F F

Cl

SMe

FCl

S Me

FF

SbF3

72%

MeS–, MeSSMe

56%

ClSMe, hν, 26 h

42%

SF3C

Cl

F

SF3C

Cl

Cl

Scheme 24


5[91[0[1[2 Tetracoordinated carbon atoms bearing one halogen and two sulfur functions"R0CHal"SR1#1#

As in the case of many compounds described in Section 5[91[0[0[2\ much of the chemistryof compounds of this class is represented by the corresponding halothiolium salts ð55AHC"6#28\79AHC"16#040Ł[ Cases illustrated below are con_ned to systems where the chemistry is best representedby the covalently bound species[

"i# From thioacetals

Chlorination of 0\2!dithianes has been used to generate versatile 1!chloro!0\2!dithianes which areuseful for coupling reactions of this masked carbonyl[ Typical conditions involve either sulfurylchloride or N!chlorosuccinimide\ and recovered yields are high "Scheme 14# ð65BCJ442\ 66TL774\68JOC0736Ł[

S S S S

Cl

SO2Cl2, CHCl3

95%

S S

S

S S

S

Cl

NCS, PhH, 20 °C, 30 min

95%

Scheme 25

"ii# From thioformates and ortho!thioesters

Ortho!thioesters can be monochlorinated successfully using either phosphorus chlorides or acetylchloride as donors\ giving moderate yields at elevated temperatures "Scheme 15# ð50LA"537#10\66JPR06Ł[ An alternative procedure involves treatment of thioesters with a dichloromethyl aryl etherin the presence of mercuric chloride "Scheme 15#[ This procedure\ however\ is less e.cient in that itrequires 1 equivalents of thioester ð61RTC238Ł[

SMe

MeS SMe

SEt

EtS SEt

O

SPh

S

F3C Cl

S

ClF2C F

SMe

Cl SMe

SEt

Cl SEt

SPh

Cl SPh

S

SCl

CF3

Cl

CF3

S

SF

CF2Cl

F

CF2Cl

OPCl3

O

MeCOCl, 70 °C

63%

CCl4, 78 °C, 1 h

70%

0.5 PhOCHCl2, HgCl2, 90 °C

80%

UV irradiation, 3 h, Cl2CF2

93%

UV irradiation, 3 h, Cl2CF2

83%

Scheme 26


"iii# Dimerization of thiocarbonyl compounds

A variety of substituted thiocarbonyl compounds are reported to undergo rapid dimerization onirradiation with UV light ð54JOC0264Ł[ The corresponding 0\2!dithietanes are formed in high yields\and are easily puri_ed by distillation "Scheme 15#[

5[91[0[2 Halogen and Se or Te Derivatives "R0CHal1SeR1 or R0CHal1TeR1#

5[91[0[2[0 Tetracoordinated carbon atoms bearing two halogens and one selenium function"R0CHal1SeR1#

A variety of examples of compounds from this class have been reported\ and their preparationoften involves transmetallation reactions of metal selenyl dihalomethyl derivatives[Bis"penta~uoroethyl# monoselenide has been prepared by reaction of selenium powder with thecorresponding penta~uoroethyl silver salt ð52JCS0157\ 62JCS"D#1203Ł[ Thermolysis of selenium metalwith tetra~uoroethylene in the presence of catalytic amounts of iodine\ however\ results in theformation of a mixture of octa~uoroselenolane and octa~uoro!0\3!diselenane "Scheme 16#ð51JOC2473Ł[ Tetra~uoroethylene also reacts with tetraselenium bis"hexa~uoroarsenate"V## overextended periods of time to yield bis"per~uoroethyl# diselenide in good yield "Scheme 16#ð66CJC2025Ł[ Similar reactions have been perfomed using Se7"AsF5#1\ and Se7"Sb1F00#1\ which bothreact with tetra~uoroethylene to give the bis"per~uoroethyl# diselenide in nearly quantitative yieldð62JCS"D#1203Ł[ Reaction of selenium metal with tri~uoroiodomethane results in the formation ofbis"tri~uoromethyl# mono! and diselenide ð47JCS1828Ł[ Similarly\ reaction of silver hepta~uoro!butyrate with selenium metal results in the formation of hepta~uoropropyl mono! and diselenideð48ZOB831Ł[ Reaction of this diselenide with mercury results in the formation of bis"hepta~uoro!propylseleno#mercury\ which is a versatile alkylseleno transfer agent "Scheme 16# ð52JCS0157Ł[Treatment of this\ and related mercurials\ with iodine results in near quantitative conversion backto the bis"hepta~uoropropyl# diselenide ð54JCS6400Ł\ whereas combination with 1 equivalents ofiodosilane results in good conversion to the corresponding silyl selenide "Scheme 16# ð51JCS1189Ł[Diselenides also react with manganese pentacarbonyl hydride to yield the corresponding organo!selenium manganese complexes ð54JCS6404Ł[ It has been reported that chlorination of 1\4!dibromo!selenophene results in the formation of 1\4!dibromoselenophene!1\2\3\4!tetrachloride\ although nodetails of conditions or yield were provided ð25BCJ046Ł[ Diphenyl diselenide reacts under dissolvingmetal reduction conditions to form an intermediate sodium selenide[ This species can be interceptedwith per~uoroalkyl iodides under photolytic conditions to yield per~uoroalkyl selenides in moderateyield "Scheme 16# ð66ZOR1997Ł[ Bis"per~uoroethyl# monoselenide reacts with iodine monochlorideto form di~uoro"per~uoroethyl#selenium in quantitative yield ð65JFC"6#150Ł[ Selenocarbonyl di~u!oride is reported to undergo addition with amines to yield an unstable amino di~uoromethyl adductð89JOM"275#210Ł[ Tri~uoromethyl selenocarbonyl ~uoride "Se1C"F#CF2#\ produced by thermal 0\1elimination of trimethyltin ~uoride from trimethylstannylpenta~uoroethylselenane\ is also reportedto undergo similar addition reactions ð89JOM"275#210Ł[ Di~uoromethyl selenoethers ArSeCHF1 canbe prepared from chlorodi~uoromethane and ArSe− ð74S386Ł[

5[91[0[2[1 Tetracoordinated carbon atoms bearing two halogen and one tellurium function"R0CHal1TeR1#

Di~uoromethyl compounds of tellurium were unknown until the mid!0889s[ A general protocolhas been reported in which dimethyl telluride is reacted with either a bis"tri~uoromethyl# cadmiumor tri~uoromethylzinc bromide in the presence of acetonitrile and boron tri~uoride "Scheme 17#ð83AG"E#212Ł[ The route is reported to be general for all chalcogens\ thus in a similar manner\ methyl"di~uoromethyl# selenide is also formed^ however\ isolated yields were not reported in either case[Per~uoroalkyl tellurides\ however\ have been prepared by a variety of means ð64JCS"D#377Ł[ Onemethod involves reaction of per~uoroalkyl radicals on a tellurium mirror\ giving low yields ofper~uoroalkyl ditelluride ð52AJC611Ł[ A more e.cient method for the preparation of bis~uoroethylmonotelluride is to react tetra~uoroethylene with Te3"AsF5#1 in a Monel reactor "Scheme 17#[ Thismethod is general\ and manipulation of conditions allows formation of varying amounts of the


F

F F

F Se Se

Se

F

F F

FF3C Se

Se CF3

F F

F F

SeCF3

F F

HgSe

F3CFFFF

F F

OAgF3CFF

F F O

SiSe C2F5

F F

H

HH

FF

PhSe CF3

F F

5%

Se4(AsF6)2, 14 d, 25 °C

87%

10%

+Se, I2, 250 °C, 7 h

PhSe

SePh

i, Se, 280 °C, 2 h

ii, Hg, 48 h 99%

+ HgI2Hg(SeC3F7)2

2 SiH3I, 25 °C

71%

i, Na, NH3(liq.)ii, C3F7I, hν

50%

Scheme 27

corresponding ditellurides ð64JCS"D#377Ł[ Per~uoroalkyl tellurides have also been prepared fromlithium aryl tellurides "obtained by reduction of diaryl ditellurides with LiAlH3# under photo!chemical conditions "Scheme 17# ð68ZOR0450Ł[

MeTe F

FMe2Te

Cd(CF3)2, MeCN, BF3, –30 °C

F

F F

F F3C Te CF3

F FFFTe4(AsF6)2, 100 °C, 15 atm

87%

TeLi Te

F

C2F5

F

C3F7I, hν, 30 min

44%

Scheme 28

5[91[0[3 Halogen and Mixed Chalcogen Derivatives "R0CHal"OR1#"SR2##

Chemistry of these systems is chie~y described by the corresponding oxathiolium salts\ thusexcluding their detailed coverage in this section[ The reader is encouraged to consult referencesdescribing such systems ð63JHC832Ł[

5[91[1 FUNCTIONS CONTAINING HALOGEN AND A GROUP 04 ELEMENT ANDPOSSIBLY A CHALCOGEN

5[91[1[0 Halogen and Nitrogen Derivatives] General Considerations

Compounds of this general class are somewhat unstable\ with the major contributing isomericforms being the corresponding haloiminium salts\ for example\ RCHal1NR0R1\ which behaves as

40Halo`en and a Group 04 Element

RC1N¦R0R1 Hal− ð59AG725Ł[ The degree to which such quaternary salts are formed depends onthe overall basicity of the amino "and chalcogen# groups^ thus\ for most compounds of the classesRCHal1NR0R1\ RCHalNR0R1OR2 and RCHalNR0R1SR2 both species must usually be consideredwhereas\ for compounds of class RCHal"NR0R1#1\ the overriding chemistry is that of the halidesalt\ the only exceptions being in cases where "NR0R1#11 "NO1#1\ where the electron!withdrawingcapacity of the nitro groups diminishes the tendency to ionize[ Several review works discuss thisdynamic equilibrium and should be consulted further ðB!65MI 591!90\ B!68MI 591!90\ B!68MI 591!91\B!68MI 591!92\ B!68MI 591!93\ B!68MI 591!94\ 74HOU"E4#Ł[

5[91[1[0[0 Tetracoordinate carbon atoms bearing two halogens and one nitrogen function

Numerous examples exist of compounds in this category[ In many cases\ however\ the chemistryof the product is often described by the corresponding haloiminium salt ð68S130Ł[ All examplesdescribed here re~ect cases where product equilibria lie in favour of the covalent species[

"i# From imines

Addition of halocarbenes to imines has been successfully used to form 1\1!dihaloaziridines bearinga variety of substituents "Scheme 18# ð48CI"L#0105\ 51JOC2575\ 60JOC2516\ 62ZOR1235\ 63JOC047\ 65JOC2683\66ZOR0746\ 67JOC0235\ 68H"01#526Ł[ Methods for formation of the requisite dihalocarbene vary as doesthe e.ciency of the addition reaction "Scheme 18#[ Addition of ClF to imines takes place at roomtemperature\ to give N!chloro~uoroalkanes in high yield "Scheme 18# ð64IC0112Ł[

XN

Ph

XN

Ph

ClCl

N

Br Cl

PhPh

N

Ph

Ph

N

Cl Cl

Ph

N

Cl

PhCl

Cl

Cl

CHCl3, KOBut, 25 °C, 18 h

X = H, 80%; Cl, 68%; OEt, 91%

HCBr2Cl, KOBut, hexane, 25 °C, 3 h

61%

PhHgCCl2F, benzene, 80 °C, 40 h

74%

Scheme 29

"ii# From amines

A variety of halogenation procedures have been applied to tertiary amines\ yielding the cor!responding dihaloaminoalkanes with good conversion[ Yields obtained for di~uoroaminoalkanesusing electrochemical ~uorination methods are usually modest\ halogen substitution using sulfurtetra~uoride being a far superior method "Equation "09##[ Perchlorination is also an e}ectiveroute\ giving high yields of a\a!dichloroalkylamines "Scheme 29# ð48CCC3937\ 58LA"629#039\ 66JFC"8#168\79JFC"06#54\ 70AG"E#536\ 70ZAAC"363#6Ł[


F3C N CF3

F FFF

Cl

N

F

F3C

CF3

F F

ClF, 6 h, 25 °C

98%(10)

F3C NCF3

FF

CF3

NMe

Me

F N F

F F

Me

Cl N Cl

Cl Cl

Me

Cl NMe

Me

Cl NCCl3

Cl Cl

Cl

Cl Cl

electrochemical

fluorination51%

SF4

quantitative

Cl2

80%

Scheme 30

"iii# From amides and thioamides

Treatment of formamides with chlorinating agents such as thionyl chloride and phosgene oftenresults in formation of dichloroaminoalkanes which exist in equilibrium with the derived chloro!iminium salts "Scheme 20# ð48HCA0542\ 53CB0250\ 68MI 591!91Ł[

R

NH

N

R

Cl

Cl

Cl

R

NH

N

R

Cl

Cl

R

NH

NCHO

R

MeN

Me

Cl

Cl

98%

Me

NMe

+

+

Cl

COCl2

Me

NMe

+Cl–

O

R = Me, 80%; Ph, 92%

Cl–

SOCl2Cl–

Scheme 31

Many such systems of this class have been prepared where electron!withdrawing groups limit thepossibility of salt formation[ A wide range of halogenation protocols have been successfully used inthese instances\ with a generally high level of conversion to product[ These methods are useful notonly for amides but also for thioamides "Scheme 21# ð59JA432\ 51JA3164\ 63JA814\ 64IC0112\ 65ZOR1102\67CB810\ 67JOC0616\ 68AG"E#504\ 70JFC"07#82\ 71PJC0258Ł[ Treatment of DMF with carbonyl di~uoride isalso reported to give a good "71)# yield of di~uoro"dimethylamino#methane ð51JA3164Ł[

"iv# From acyl halides

Treatment of acyl ~uorides with tetra~uorohydrazine under photolytic conditions results information of the corresponding N\N!di~uoroaminoalkane "Equation "00##[ One drawback of thisradical addition protocol is the requirement that quartz reaction vessels be used ð57JOC2564Ł[


O

F3C N CF3

CF3

F3C N CF3

CF3Cl ClPCl5, 25 °C, 6 h

99%

O

F15C7 NCF3

CF3

F15C7 NCF3

CF3

F FSF4, HF, 150 °C, 18 h

78%

O

NMe

Me

NMe

Me

F

FFCOF, 25 °C, 20 h

82%

NMe

Me

O

NMe

Me

F F

SF4, KF, 150 °C, 144 h

90%

O

F3C NEt

Et

F3C NEt

Et

Cl ClCl2, CCl4, 20 °C

70%

Scheme 32

O

C3F7 FC3F7NF2

N2F4, 40 h, 20 °C, hν

90%(11)

"v# From nitriles

Chloro~uorination of nitriles is a mild and convenient method for preparation of N\N!dihalo!aminoalkanes[ The reactions have only been reported for nitriles bearing electron!withdrawinggroups\ but yields are good to excellent "Scheme 22#[ The intermediate haloimine can be exposed toelemental ~uorine to give N!~uorochloroamines or it can be reacted sequentially with ClF to yieldN\N!dichloroamines ð55IC377\ 68JA6539\ 70IC0Ł[ Addition of hydrogen ~uoride to a mixture of HCNand carbonyl ~uoride\ catalyzed by caesium ~uoride\ is reported to yield di~uoromethylcarbamoyl~uoride\ CHF1NHCOF "69)# ð51JA3164Ł[ Treatment of per~uorinated cycloalkyl nitriles with silver~uoride at elevated temperature is reported to yield the corresponding per~uorinated cyclo!alkylmethylazo compounds ð73JCS"P0#344Ł[

R N NCl

F

R

N

Cl

ClR

F F

N

Cl

FR

F F

ClF, 0 °C

F2, –25 °C, 1 h

R = CF3, 75%; ClF2C, 70%

ClF, –195 °C

Scheme 33

"vi# From haloiminium salts

Treatment of haloiminium salts with hydrogen halides provides a facile route to a!dihaloamines"Equation "01##[ The reactions are typically conducted at or below 9>C in chlorinated solvents\ and


yields of addition products\ which are in equilibrium with their corresponding hydrohalide salts\are good to excellent ð50CCC2948\ 51CCC1775\ 52CCC1936Ł[

N

X

X Me

Me

N

X Me

Me

X–+ HX, CHCl3, 0 °C

X = Br, 98%; I, 82%; Cl, 77%(12)

"vii# From haloalkenes and haloalkanes

Addition of diethylamine to chlorotri~uoroethene results in the formation of the correspondingdiethylaminoalkane in moderate yield "Equation "02## ð70AG"E#536Ł[ The product\ 1!chloro!0\0\1!tri~uorotriethylamine "CTT#\ is a ~uorinating agent ð48JGU1014Ł[ A similar addition reaction hasbeen applied to related secondary amines ð70JFC"07#82Ł[ N!Iodobis"ditri~uoromethyl#amine isreported to add to hexa~uoropropene under photochemical conditions to give "F2C#1NCF1CFICF2

in low yield ð60JCS"C#2722Ł[ ð2¦1Ł Cycloaddition of benzyl azide to hexa~uoropropene gives anintermediate triazoline in 74) yield\ which undergoes thermal decomposition at 149>C to give thecorresponding 0!benzyl!1\2\2!tri~uoro!1!"tri~uoromethyl#aziridine "63)# ð55JOC678Ł[ Cyclo!addition of per~uorobutadiene to tri~uoronitrosomethane is reported to give per~uoro!1!methyl!2\5!dihydro!0\1!oxazine in 59) yield ð54JCS5038\ 55ZOB617\ 56JCS"C#1152Ł[ The azido esterBrCF"N2#CO1Et has been prepared "36)# by reaction of ethyl dibromo~uoroacetate with sodiumazide ð75JOC844Ł[

ClN

Et

F

F F

Et

Cl

F F

F

Et2NH

61%(13)

CTT

"viii# Routes speci_c to dihalonitroalkanes

"a# From nitromethanes[ Di~uoronitromethane reacts with formaldehyde under basic conditionsto give 0\0!di~uoro!0!nitroethanol in 77) yield "Scheme 23# ð56ZOB041Ł[ Reactivity of its stabilizedanion extends to Michael!type processes\ but only moderate yields of addition products are obtainedeven for addition to such activated systems as acrylonitrile and ethyl acrylate ð68IZV0800Ł[ Dibromo!nitromethane is reportedly formed when nitromethane is exposed to t!butyl hypobromiteð65JOC0174Ł\ and 0\0!dibromoethane has been prepared from nitroethane by sequential reactionwith butyllithium and bromine ð78ZOR1389Ł[

F

F NO2

HOF

FNO2

X F

FNO2

F

F NO2

X

HCHO, K2CO3, H2O

88%

, NaOEt, K2CO3

X = CO2Et, 27%; CN, 13%

Scheme 34

"b# From haloalkenes[ Fluoroalkenes are reported to react with sodium nitrite in polar aproticsolvents to furnish ~uoronitroalkanes in moderate yield "Scheme 24# ð63IZV1033Ł[ Similar additionreactions can be accomplished using perhaloalkenes and a mixture of concentrated nitric andhydro~uoric acids ð52IZV0835Ł[ 0\1!Dichloro!0\1!di~uoroethylene is converted by nitration followed


by reaction with fuming nitric acid into chloro~uoronitrosomethane\ which can then be oxidized tochloro~uoronitromethane ð89MI 591!90Ł[

F3COF

F

F3CO

F F

F FNO2

NaNO2, DMF, 3 d

50%

ClF

F

Cl

F F

F FNO2

FHNO3 (100%), HF, 20 °C, 7 h

88%

Scheme 35

"c# From nitro alcohols[ 1!Fluoro!1!nitro!0!butanol reacts with aqueous sodium hypobromite togive 0!bromo!0!~uoro!0!nitropropane "Equation "03##[ The reaction is believed to proceed via atransient a!~uoronitronate salt ð69JOC735Ł[

EtOH

F NO2

Et Br

F NO2NaOBr, NaOH (aq.), 10 °C, 40 min

57%(14)

5[91[1[0[1 Tetracoordinate carbon atoms bearing one halogen and two nitrogen functions

In all cases in which the nitrogen functions are amino groups\ attempts to prepare compounds ofthis class results in the formation of the corresponding haloiminium salts[ Examples are widespread\covering simple amines ð54CB0967\ 62LA39\ 64LA084Ł\ cyclic amines ð50CB1483\ 58RTC178Ł and hydra!zines ð60JOC0044Ł[

One class of compounds within this category which retains stability\ however\ are the halo!diazirines "Scheme 25#[ Typical conditions involve exposure of an acetamidine to bromide saturatedDMSO with sodium chlorite] the so!called {Graham conditions| ð54JA3285\ 56JA071\ 57JOC0736\70JA5053\ 76TL4790\ 78ACR04Ł or treating N\N!dihaloamidines with base "Scheme 25# ð70JOC4937Ł[

NN

ClR

N

R NHCl

Cl

NN

BrF3C

N

F3C NH2

H NN

FF3C

TRIGLYME, DMSO, 10% NaOH, NaCl, 0 °C

R = Pri, 49%; MeO, 43%

NaOCl, NaBr

DMSO, LiBr30%

tbaf, MeCN

50%

Scheme 36

"i# Tetracoordinate carbon atoms bearin` one halo`en and two nitro `roups "RCHal"NO1#1#

Nearly all compounds in this class have been prepared from the salts of dinitroalkane anions\reacting with a halogenating agent[ They are grouped according to the nature of the halogenationprocedure employed[

"a# Usin` elemental halo`ens[ Typically\ conditions involve formation of the potassium salt ofthe dinitroalkane\ followed by exposure to the halogen source in situ[ The salts are either preparedby treating the dinitroalkane with the required potassium base or\ in the case of dinitromethane\via a Ter Meer reaction with chloronitromethane\ itself available by chlorination of nitromethane[The most commonly used procedure is to pass a ~uorineÐnitrogen mixture into the aqueous solutionof the salt at or close to 9>C "Scheme 26# ð57IZV320\ 57IZV1296\ 58IZV0220\ 62IZV0313\ 67JOC2374Ł^ xenondi~uoride is also e}ective as a ~uorinating agent ð76ZOR0546Ł[ Similarly high yields have also


been obtained using the sodium or ammonium salts of dinitroalkanes ð57IZV801Ł and of 1\1!dinitropropane!0\2!diol in which one of the hydroxymethyl groups is cleaved "Scheme 26#ð57JOC2979Ł[ Chlorination of the sodium salts are also reported to give excellent yields of the derivedchlorodinitroalkane "Scheme 26# ð58IZV1506\ 76IZV295Ł\ and bromodinitromethane has been preparedby reaction of the sodium salt of dinitromethane with bromine[ ICl has been used to form thecorresponding iododinitroalkanes ð66IZV1947Ł[

NO2

R NO2

NO2

R NO2

F

NO2

NO2

NO2

R NO2

I

F2, H2O, 0–5 °C

ICl, CCl4, 10–15 °C

76%

F

O2N NO2O2N NO2

F2, N2, H2O, 1 h, 2–3 °C

90%

NO2

NO2

NO2

NO2

F

HO OHO2N NO2

HONO2

NO2F

–K+

NO2

NO2

–K+

–Na+ NO2

NO2

NH4+

Cl

+ NH4F–

NaOH, H2O, F2, 2 h, 0–5 °C

82%

NaOH, H2O, F2, 2.5 h, 0–5 °C

84%

Cl2, 0–5 °C

99%

Scheme 37

R = H, 65%; CH2CH2CN, 60%; CH2C(NO2)2, 81%; p-C6H4NO2, 62%; m-diC6H3NO2, 92%

"b# Usin` perchloryl ~uoride[ Most work in this category has been conducted using potassiumsalts of the dinitroalkanes\ providing a generally high yielding approach to the desired ~uoro!dinitroalkanes "Equation "04## ð57JOC2962\ 69IZV276\ 60IZV0376Ł^ similar results "albeit with inferioryields# are obtained using sodium salts ð61JOC041Ł[ For systems where the corresponding salts ofdinitroalkanes are unstable\ use of hexamethylphosphoramide "HMPA# and perchloryl ~uoride isreported to allow e.cient ~uorination within 1 hours "Scheme 27# ð58IZV0077Ł[ Interestingly\exposure of ClOSO1F to cyano!substituted dinitroalkane salts results in formation of the derivedN!chloroimidates "Scheme 27# ð65IZV378Ł[

NO2

R NO2

–K+

NO2

R NO2

FFClO3, MeOH, 25 °C

R = Ph, 95%; CH2CH2CO2Me, 88%; CH2NHCOPh, 88%; CH2CH2NHCOMe, 93%; CH2CH=CH2, 69%

(15)

"c# Usin` hydro`en halides[ Treatment of sulfonium dinitroylides with hydrogen halides resultsin rapid formation of the corresponding halodinitroalkane "Equation "05##[ The cleavage method isapplicable to a range of electrophilic halogen sources including elemental halogens and hypohalites\with a dialkyl sul_de being the chief by!product ð66IZV028Ł[

NO2

S NO2Me

Me

NO2

X NO2

–+ + Me2Sexcess HX, MeCN

X = Br, 76%; Cl, 89%(16)


O2N NO2

NO2 NO2

O2N F

NO2NO2

F NO2FClO3, HMPA, 2 h, 20 °C

88%

NC NO2

NO2

– Na+

O2NN

Cl

NO2Cl

OSO2F

ClOSO2F, 16 h, 20 °C

66%

Scheme 38

"d# Functional `roup interconversion of dinitrohaloalkanes[ The ~uorodinitromethanide anionundergoes a variety of additional transformations relevant for this section[ Most importantly\ underbasic conditions\ 0\ 1 additions to aldehydes are possible to yield secondary alcohols ð69JOC2077Ł\as are 0\ 3 additions to conjugated alkenes ð68S200Ł\ giving high yields of addition products in bothcases[ Related examples of compounds incorporating this functionality where the dinitrohalo groupis left intact include acid!catalyzed dimerization of dinitro~uoroalcohols ð58JOC34Ł\ hydrolysis of~uorodinitroacetonitrile to yield ~uorodinitroacetamide ð57JOC0146Ł and dehydroxymethylation of1\1!dinitro!1!~uoroethanol ð58JOC34Ł[

"ii# Tetracoordinate carbon atoms bearin` one halo`en\ one nitro `roup and one other nitro`enfunction

An example of this class is the ester BrC"N2#"NO1#CO1Et\ which was obtained in low yield fromethyl dibromonitroacetate by reaction with sodium azide ð75JOC844Ł[

5[91[1[0[2 Tetracoordinate carbon atoms bearing one halogen\ one nitrogen and one oxygen function

Based on the previous discussions concerning the stability of ortho!ester halides attached to basicfunctionality\ salt formation is predominant[ Probably the best studied example of this class is theVilsmeier reagent and related systems\ formed when formamides are exposed to chlorinating agents"Scheme 28# ð47CCC341\ 48HCA0548Ł[ The equilibrium lies heavily in favour of salt formation\ explain!ing in this case\ and related examples ð58TL1050\ 60CPB1518Ł\ why members of this class have receivedscant attention[ Other examples can be found describing intermediate formation of this class ofcompound\ which quickly undergoes rearrangement to give the halide salt ð57JOC0973\ 69CPB673\61TL3106\ 62TL3400\ B!68MI 591!92\ 79IZV1245Ł\ and in some cases to give enamines ð54JOC3292\ 57T3106Ł[

RN Cl

R

OPOCl2

RN

R

O

RN Cl

R

RN OPOCl2

R

+[PO2Cl2]–

Cl–

POCl3, CH2Cl2

+

Scheme 39

5[91[1[0[3 Tetracoordinate carbon atoms bearing one halogen\ one nitrogen and one sulfur function

Compounds of this class in which the nitrogen function is an amino group are nearly alwaysfound in the form of the corresponding iminium halide salt ðB!68MI 591!94Ł[ The exceptions arenitrohalosul_des[ 0!Chloro!0!chlorosulfenylnitroalkanes have been reported ð74HOU"E4#Ł and theesters PhS"NO1#CXCO1Et "X�Br\ and F# have been prepared by halogenation of the ester PhS!"NO1#CHCO1Et ð75JOC844Ł[


5[91[1[1 Halogen and Phosphorus Derivatives

5[91[1[1[0 Tetracoordinate carbon atoms bearing two halogen and one phosphorus function and onehalogen and two phosphorus functions

"i# From haloalkenes

Addition of phosphine to ~uoro and chloro~uoroalkenes is a general route to compounds of thisclass[ Generally\ the addition reactions are conducted at elevated temperatures\ often in sealedtubes[ Phenylphosphine has also been employed\ with only slight loss of e.ciency resulting "Scheme39# ð48JA3790\ 54AFC"3#49Ł[ If the reactions are conducted under photolytic conditions\ however\yields are often substantially improved\ with 73) for the addition to tetra~uoroethylene reportedð52JCS0972Ł[

X

F F

F

FP

H

X H

F FPH3, 150 °C, 8 h

X = F, 53%; Cl, 54%

F

F F

F

FP

Ph

F H

F FPPhH2, 150 °C, 8 h

45%

Scheme 40

"ii# From haloalkanes

Thermolysis of carbon tetra~uoride with red phosphorus in the presence of iodine results in theformation of a cyclic bis"phosphine# in moderate yield "Scheme 30# ð51JOC2473Ł[ 1\1\1!Trichloro!acetic amidines and imidates react with trialkyl phosphites to yield 1\1!dichloro!1!"dialkoxyphos!phinyl#acetamidines and acetimidates\ respectively "Scheme 30# in good to high levels of conversionð68ZOB0914Ł[ If the reactions are prolonged\ a second substitution occurs giving amonohalobis"dialkylphosphinyl# derivative[ Addition of chlorodi~uoromethane to sodiumdiethylphosphonate results in the formation of diethyl di~uoromethylphosphonate ð48JGU0004Ł[The mechanism of this reaction appears to involve capture of di~uorocarbene rather than an SN1type process[ Prompted by research on purine nucleoside phosphorylase inhibitors\ it has beenshown that diethylphosphinyldi~uoromethyllithium condenses with ortho!a!bromoxylene to givethe corresponding di~uorophosphonate in 32) yield "Scheme 30# ð81BMC396Ł[ Interestingly\ othermetal dialkylphosphinyldi~uoroalkane derivatives proved vastly inferior in this reaction[Diisopropylphosphinyldi~uoromethyllithium was shown to give good yields of the 0\1!additionproduct to o!tolualdehyde at low temperature "Scheme 30#^ the benzylic alcohol was subsequentlyconverted into the tri~uoro derivative using diethylaminosulfur tri~uoride ð81BMC396Ł[ Diethyl"lithiodi~uoromethyl#phosphonate has also been used to introduce the a\a!di~uorophosphonatemoiety into phosphate isosteres ð81TL0728\ 83TL2116Ł[ Though alkyl halides are often poor substratesin such coupling reactions\ Martin has reported conditions for addition to aldehydes\ where theresulting product carbinols are deoxygenated using a Barton!type protocol ð81TL0728Ł[ The processis versatile\ tolerant of latent functionality\ and complements existing methods for the introductionof this important moiety ð70JFC"07#086\ 71TL1212\ 78JOC502\ 78TL6902\ 80TL0908Ł[ Dialkyl "iodo~uoro!methyl#phosphonates\ available from dialkyl "bromodi~uoromethyl#phosphonates\ are reported toundergo reductive dimerization to yield tetra~uoroethyl derivatives using cadmium powder\ re~ux!ing in methylene chloride "Scheme 30# ð83JOC1282Ł[ The corresponding dialkyl "bromo!di~uoromethyl#phosphonates fail to undergo this coupling using cadmium\ but this was _nallye}ected using a nickel derivative[ The nickel approach also facilitated dimerization of a dialkyl"iodotetra~uoroethyl#phosphonate\ giving the coupled product in 37) yield ð83JOC1282Ł[ Theaddition of diethyl trichloromethylphosphonate to alkenes\ catalyzed by copper chloride\ has beenreported ð83TL2426Ł[ Ethyl acrylate thus gives the corresponding dichlorophosphonate in moderateyield "Scheme 30#[


P

P

I

I

F

F

F

F

FF

FF

O

PRO NH2

NH

ClCl

ROCl

NH2

NH

ClCl

O

PRO OMe

NH

ClCl

ROClOMe

NH

ClCl

O

PEtO NH2

NH

ClP

EtOCl

NH2

NH

ClCl

O

EtO

EtO

Br

P

O

F FOEt

OEt

Li P

O

F FOEt

OEt

CHO P

O

F FOPri

OPri

Li P

O

F FOPri

OPri

OH

P

O

EtO P

O

F FOEt

OEt

EtO

F F

PEtO

IEtO

F F

O

P

O

MeO P

O

F FOMe

OMe

MeO

F F

PMeO

BrMeO

F F

O

P

O

EtO

EtOP

EtO

EtO

F F

O

Br

FF

O

OEt

OEtP

F F

F F

F F

FF

EtOP

OEt

OOEt

ClClCl

O

P(red), I2, 220 °C, 8 h

28%CF4

EtO

O

(RO)3P, CH2Cl2, 50 °C, 1.5 h

R = Et, 84%; Prn, 62%

(RO)3P, CH2Cl2, 50 °C, 1.5 h

R = Et, 70%; Prn, 85%

Cl POEt

OOEt

, THF, –78 °C

43%

Cd, CH2Cl2

69%

80%

ClCl

(EtO)3P, CH2Cl2, 85%, 2 h

62%

Zn, NiCl2(PPh3)2Et4NI, MeCN, 45 °C

48%

Zn, NiCl2(PPh3)2Et4NI, MeCN, 45 °C

47 %

, CuCl

59%

Scheme 41


5[91[1[2 Halogen and Arsenic Derivatives

5[91[1[2[0 Tetracoordinate carbon atoms bearing two halogens and one arsenic function

Dimethylarsine is reported to add to hexa~uoropropene to give the corresponding dimethylarsenicderivative "Scheme 31# ð54AFC"3#49Ł[ Unfortunately\ no details either of yield or of conditions forthis process were reported[ Another report describes the reaction of tetramethyldiarsine "{cacodyl|#with hexa~uoropropene to produce a ~uorodiarsine in 07) yield "Scheme 31# ð53CJC0012Ł[

F

CF3F

FMe

AsMe CF3

F

FF

Me

AsMe As

FF3C

F FMe

Me

Me2AsH Me2AsAsMe2

18%

Scheme 42

5[91[2 FUNCTIONS CONTAINING HALOGEN AND A METALLOID AND POSSIBLY ACHALCOGEN AND:OR GROUP 04 ELEMENT

5[91[2[0 Halogen and Silicon Derivatives

A variety of a\a!dihaloalkylsilanes are known but few general methods for their preparation existð53CB0562Ł[ The following examples cover speci_c cases where conditions have been examined andoptimized[

"i# Dichlorocarbene additions

Addition of dichlorocarbene "generated from phenyl"bromodichloromethyl#mercury# to a varietyof silanes has been reported\ giving good yields of a dichloromethyl silanes "Scheme 32#[ Competitionexperiments have been carried out in order to determine the kinetics and the precise mechanism ofthis electrophilic addition process ð56JA0427\ 57JA1833\ 82T7376Ł[

SiSi Me

Me

Me MeCl

ClPhHgCCl2Br, PhH, 80 °C

58%

Si H

Me

Si

MeCl

Cl

PhHgCCl2Br, PhH, 80 °C

68%

R

SiMe

MeH

R

Si Cl

Cl

Me Me

PhHgCCl2Br, PhH, 80 °C

34–67%

Scheme 43

"ii# Other additions to silanes

Low temperature metal halogen exchange of bis"trimethylsilyl#dichloromethane followed byprotonation has been used to prepare bis"trimethylsilyl#chloromethane "Scheme 33# ð60JOM"18#278\89T2748Ł[ Bromination of alkynylsilanes has also been reported\ the major isolated addition productbeing the tetrabromosilane in nearly quantitative yield "Scheme 33# ð56IZV582Ł[ An alternative

50Halo`en and a Metalloid

approach to dihalosilanes is cleavage of a bis"trichloromethylsilyl#dichloromethane using hydro!chloric acid "Scheme 33#\ with the a\a!dichloromethylsilane being formed in 76) yield ð53CB0004Ł[Another report describes alkyl Grignard addition to trichlorosilyldichloromethane\ which yieldsusing methylmagnesium bromide\ trimethylsilyldichloromethane "50)# ð55CB682Ł[ Photochemicaladdition of silyl radicals to per~uorinated alkenes has also been employed\ UV irradiation of silanein the presence of tetra~uoroethylene giving a 50) yield of 0\0\1\1 tetra~uoroethylsilane in 07 hð54JCS1090Ł[ Similarly\ photochemical addition of the chlorosilyl radical derived from methyl!dichlorosilane to tetra~uoroethylene results in a 87) yield of the a\a!di~uorosilane adductð57ZOB1702Ł[ Lithiation of 0\5!dibromodeca~uorohexane\ followed by addition of trimethylsilylchloride\ results in formation of 0\5!bis"trimethylsilyl#deca~uorohexane in 55) yield ð58JOM"05#22Ł[

TMS TMS

Cl Cl

TMS TMS

Cl

Si

Me

Me

MeMe

SiBr

MeMe

Br

BrBr

TMS SMe TMS SMe

Cl

CH2Cl2 + 2 TMS-ClBunLi. –110 °C

64%

TMS SMe

i, BunLi, –110 °C

ii, EtOH, –65 °C 73%

OMe

Cl2(SiCl3 )2

Br2, 50 °C, then 80 °C, 12 h

97%

TMS OMe

HCl

87%

Cl

NCS, CCl4

60%

Cl2CHSiCl3 + SiCl4

Cl2, CCl4, Et3N

69%

Scheme 44

Preparation of systems containing a metalloid\ halogen and chalcogen have also been reported[Chlorination of "methylthiomethyl#trimethylsilane has been accomplished\ giving ðchloro!"methylthio#methylŁtrimethylsilane in 59) yield "Scheme 33# ð78T526Ł[ Additionally\ðmethoxy"methylthio#methylŁtrimethylsilane "itself prepared from ðchloro"methylthio#methylŁtrimethylsilane by addition of sodium methoxide# has been converted to ðchloro"methoxy#methylŁtrimethylsilane "Scheme 33# in 58) yield\ using traditional chlorination conditions ð78T526Ł[

5[91[2[1 Halogen and Boron Derivatives

Compounds of this class are extremely unstable\ which accounts in part for their general lack ofutility in synthesis[ The general mechanism for the decomposition of a!bromoalkylboranes "formedfrom trialkylboranes and bromine# appears to involve HBr!induced cleavage which may proceedvia a radical pathway\ rather than by simple rupture of the C0B bond ð69JA6101Ł[ Treatment ofa\a!dihaloalkylboranes with nucleophiles such as water also induces rearrangement\ providing aroute\ after oxidation\ to secondary alcohols ð60JA1685Ł[ An a\a!dichloroalkylborane was preparedby Seyferth by dichlorocarbene insertion into a trialkylborane "Scheme 34#^ however\ spontaneousrearrangement occurred with subsequent elimination from the chloroborane species ð55JA0723Ł[ Itis reported that the stability of the intermediate a\a!dichloroalkylborane is a function of the boraneR group\ and that triarylboranes "R�Ph# yield the more stable adducts[

R3BPhHgCCl2Br

70 °C, 40 min

R

BR

R

ClCl

R

BCl

R

RCl

R = Prn, Bun, Ph

Scheme 45


5[91[2[2 Halogen and Germanium Derivatives

Trichlorogermane has been shown to undergo addition to chlorinated alkenes\ and this constitutesan excellent route to a\a!dichloroalkylgermanes "Scheme 35# ð59DOK"020#87Ł[ Photochemical chlori!nation of alkylgermanium compounds has also been reported\ giving moderate yields of the a\a!dichloro species "Scheme 35# ð56ZOB0939Ł[ Bis"per~uoroalkyl#mercury compounds have been shownto react with germanium tetrahalides to produce per~uorogermanium alkyls in good yield "Scheme35# ð67JA0611Ł[ The trihalo"per~uoroalkyl#germanium compounds produced are versatile syntheticintermediates\ since they react with dialkylcadmium reagents to give alkyl "per~uoro!alkyl#germaniums ð67JA0611Ł[ Bis"triethylgermyl#mercury undergoes exchange with bis"halo!alkyl#mercury compounds\ to yield mixed haloalkyl "triethylgermyl#mercurials ð61JOM"23#188Ł[These mixed mercurials react with caesium ~uoride to produce haloalkyl germaniums in goodyield "Scheme 35# ð61JOM"23#188Ł[ Bis"trialkylgermyl#mercury reacts with bis"haloalkyl#mercurycompounds to produce a variety of mixed haloalkyl germanium species ð61IZV74Ł[ The intermediateis presumably a mixed "triethylgermyl#mercury species\ and the isolated yields are good to excellentð61IZV74Ł[

Cl

ClGeCl3

ClClCl

Cl Cl

Cl

F3CGeCl3

ClClF3C

GeCl3

G eEt

CF3

FF

Et

GeEt

CF3

FCl

Et

GeBr

CF3

FF

Br

HGeCl3, 80 °C, 2 h

48%

GeI

CF3

FF

CsF, THF, 5 min

75%

I

Cl2, hν

58%

(C2F5)2Hg

Et3GeHgCFClCF3

(C2F5)2HgGeI4, 135 °C

53%

CsF, THF, 5 min

75%

GeBr4, 195 °C

45%

Et3GeHgC2F5

Scheme 46

Et

Et

Br

I

5[91[3 FUNCTIONS CONTAINING HALOGEN AND A METAL AND POSSIBLY AGROUP 04 ELEMENT\ A CHALCOGEN OR A METALLOID

5[91[3[0 Halogen and Lithium Derivatives

Under the general heading of {lithium carbenoids|\ haloalkyllithium compounds have enjoyedwidespread use due to their unusual reactivity and their ability to deliver the versatile halomethylenefunctional group to suitable acceptors[ A critical aspect of these species is the role of solvent usedin their preparation\ THF being the solvent of choice\ owing to its ability to stabilize the carbenoidspecies[ However\ the increased viscosity of THF at the low temperatures typically employed togenerate carbenoids sometimes poses problems\ and often ether or petroleum ethers are used as co!solvents[ Typical conditions involve treating a dilute solution of either a dihaloalkane or a tri!haloalkene at −099>C with an alkyllithium reagent in THF "Scheme 36# ð54JA3036\ 54TL858\ 82T7376Ł[Since the carbenoids are typically thermally unstable "decomposing completely above −54>C#\ in

52Halo`en and a Metal

situ reaction with a suitable electrophile is usually carried out\ otherwise intramolecular carbenoidinsertions may take place[ Examples of lithiodi~uoroalkanes are common\ available either bymetallation of di~uoroiodoalkanes at low temperature ð74TL4132Ł or by metallation of di~uoro!alkanes with lithium amide bases at elevated temperature ð66JOC454Ł[ Terminal lithioper~uoro!alkanes often undergo spontaneous elimination of LiF to yield per~uorinated alkenes ð74TL4132Ł[The alkoxycarbenoid ClCH1CH1OCHClLi has been generated and used to cyclopropanate cyclo!hexene ð58OS"38#75\ 61JA014Ł[

I

I Li

Cl

Cl Li

CH2I2LDA, –78 °C, THF, 30 min

PhCCl3PhBuLi, THF, –100 °C

Scheme 47

5[91[3[1 Halogen and Magnesium Derivatives

Transmetallation reactions between Grignard reagents and perhalogenated systems is a versatileroute to compounds of this class[ Thus phenylmagnesium bromide reacts with 0!iodohepta~uoro!propane at low temperature to produce hepta~uoropropylmagnesium bromide in good yield "Sch!eme 37# ð46JA2240Ł[ Such Grignard reagents are useful for addition of perhaloalkyl functionality tocarbonyl compounds ð77BCJ2210Ł[ Other examples of this transmetallation protocol demonstrate itssynthetic utility "Scheme 37# including formation of bis"bromomagnesium# compoundsð64JFC"4#364Ł[

MgBr

FF

F3C

FF

I

FF

F3C

FF

PhMgBr, –78 °C, Et2O+ PhI

BrMg MgBrF F

FF

FF

I IF F

FF

FF

2 RMgBr, –70 °C, Et2O

Scheme 48

5[91[3[2 Halogen and Copper Derivatives

Reaction of copper metal with terminally iodo!substituted per~uoroalkanes at elevated tem!peratures results in formation of a per~uorinated alkylcopper"I# species\ together with copper"I#iodide "Equation "06## ð76JFC"26#060Ł[ Chain polymerization of these species has been reported onthermolysis in DMF ð77DIS"B#1862Ł[

F

F3C F

IF

F3C F

Cu + CuI2 Cu, DMSO, 110 °C

(17)

5[91[3[3 Halogen and Silver Derivatives

Addition of silver tri~uoroacetate to chlorotri~uoroethene in the presence of metal ~uoridesresults in the formation of an organosilver compound bearing an a\a!dihalo alkyl group "Equation


"07## ð62JOM"46#312Ł[ Caesium ~uoride is reported to promote this reaction more e.ciently thanother alkali metals[

Cl

F3C F

AgCF3CO2Ag, MF(18)

F

F F

Cl

5[91[3[4 Halogen and Zinc Derivatives

Zinc metal reacts with alkyl iodides\ chlorides and bromides to give the corresponding halozincreagents "Scheme 38# ð42JCS2596\ 46JA3048\ 73JFC"15#324\ 77JOM"228#06Ł[ Yields of organozinc reagentare heavily dependent on both concentration and temperature of reaction and\ where ethers are notemployed as solvents\ solvated products are formed\ for example\ with DMF[

F3CI

F F

F FF3C

ZnIF F

F F

F3C Cl

Zn, DMFCl

Cl

F3C Cl

ClZnCl(DMF)2

Zn, dioxane

75%

Scheme 49

5[91[3[5 Halogen and Cadmium Derivatives

Cadmium metal will insert between the carbonÐbromine or carbonÐiodine bond in mixed per!haloalkanes to yield a variety of organocadmium reagents "Scheme 49# ð77JFC"28#314\ 77JFC"30#074Ł[Alternatively\ transmetallation from dialkylcadmium reagents to dihaloiodoalkanes can beemployed to form perhalodialkylcadmium reagents of this class[

F3C Cd CF3

FF

FF + 2 MeI2 F5C2I

Me2Cd, MeCN

F

F X

F

F Cd-X

Cd, DMF, 50 °C

X = Br, 75%; I, 91%

Scheme 50

5[91[3[6 Halogen and Mercury Derivatives

Mercuric ~uoride will add to haloalkenes quite readily at elevated temperatures to yield per!halodialkylmercury compounds "Scheme 40# ð59JOC094\ 50JCS2714Ł[ Strict regiocontrol in theaddition reactions to mixed haloalkenes is usually observed[ It has been reported that per~uoro!propen!1!ol\ the meta!stable enol form of penta~uoroacetone\ reacts with mercury tri~uoroacetate

54Halo`en and a Metal

to yield tri~uoroacetoxymercuricper~uoroacetone "Scheme 40# ð64DOK"110#0220\ 65ZOR0266Ł[ Caremust be taken when handling this species\ as it is reported to undergo rapid hydration to form thecorresponding hydrate[

F

F CF3

OH

Scheme 51

(CF3CO2)2Hg, Et2O

20 °C, 12 h 79%

CF3CO2HgCF2COCF3

F3C Hg CF3

ClCl

ClCl

F

F Cl

Cl

HgF2, HF, ∆

69%

F3C Hg CF3

FF

FF

F

F F

F

HgF2, 100 °C

56%

5[91[3[7 Halogen and Tin Derivatives

Reaction of dialkyltin hydrides with tetra~uoroethylene is reported to give the 0 ] 1 adducts"Scheme 41# ð54AFC"3#49Ł[ Another route to these compounds is via insertion to iodoper~uoro!alkanes using either tin"II# chloride or tin"II# ~uoride "Scheme 41#[ The resulting organotin com!pounds retain the halogen atoms originally attached in this rapid reaction ð70CL0226Ł[ Reaction oftrimethyltin hydride with trialkyl"tri~uoromethyl#stannanes results in reduction to the cor!responding di~uoroalkyltin species "Scheme 41# ð69IC0571Ł[ Bis"per~uoroalkyl#cadmium com!pounds are reported to undergo transmetallation with Me2SnOCOCF2 to yield the correspondingper~uoro organotin derivatives "Scheme 41# ð74JFC"16#298Ł[ Tetrakis"tri~uoromethyl#germanium isreported to react with trimethyltin hydride to produce\ in addition to tris"tri~uoromethyl#germane\trimethyl"di~uoromethyl#tin in low yield ð83JOM"354#042Ł[

F

FF

F

SnF

F

F

F

F F F F

Bu Bu

Bu2SnH2

F3C(CF2)5I F3C(CF2)5SnCl2ISnCl2 (or SnF2), DMF, 25 °C

Me3SnCF3 Me3SnCHF2

Me3SnH, 150 °C

63%

(C2F5)2Cd Me3SnC2F5

Me3SnOCOCF3, 70 °C

64%

Scheme 52

5[91[3[8 Halogen and Lead Derivatives

Addition of tetramethyllead to iodopenta~uoroethane at elevated temperature results in for!mation of penta~uoroethyltrimethyllead in moderate yield "Scheme 42# ð59JA5117Ł[ In an analogousmanner to the corresponding organotin compounds\ bisper~uoroalkyl cadmium species undergo


transmetallation with Me2PbOCOCF2 to yield per~uoro organolead derivatives "Scheme 42#ð74JFC"16#298Ł[

CF3CF2I Me3PbCF2CF3

Me4Pb, 150 °C

28%

(C2F5)2Cd Me3PbC2F5

Me3PbOCOCF3, 70 °C

91%

Scheme 53


6.03Functions Containing ThreeChalcogens (and No Halogens)GLYNN MITCHELLZENECA Agrochemicals, Bracknell, UK

5[92[0 INTRODUCTION 57

5[92[1 FUNCTIONS BEARING THREE OXYGEN ATOMS 57

5[92[1[0 Methods for the Preparation of Carboxylic Ortho!esters and Related Compounds 575[92[1[0[0 Ortho!esters from 0\0\0!trihaloalkanes\ a\a!dihalo ethers and a!haloacetals 575[92[1[0[1 Ortho!esters from imidate ester salts 585[92[1[0[2 Ortho!esters from carboxylic acids and derivatives 605[92[1[0[3 Ortho!esters from dioxocarbenium salts 625[92[1[0[4 Ortho!esters from 0\0!dialkoxyalkenes\ 0\0!dihaloalkenes and 0!alkoxyalkynes 635[92[1[0[5 Ortho!esters from 0\0!dialkoxycyclopropanes and related compounds 655[92[1[0[6 Ortho!esters from acetals 665[92[1[0[7 Ortho!esters from ortho!carbonate esters and trialkoxyacetonitriles 66

5[92[1[1 Preparation of Carboxylic Ortho!Esters from Other Ortho!Esters 675[92[1[1[0 Trans!esteri_cation reactions 675[92[1[1[1 Modi_cation of R0 and R1 of R0C"OR1#2 79

5[92[2 FUNCTIONS BEARING THREE SULFUR ATOMS 70

5[92[2[0 Methods for the Preparation of Trithio!ortho!esters and Related Compounds 705[92[2[0[0 Trithio!ortho!esters from RC"X0#"X1#X2 705[92[2[0[1 Trithio!ortho!esters from thioimidate ester salts 725[92[2[0[2 Trithio!ortho!esters from carboxylic acids and derivatives 735[92[2[0[3 Trithio!ortho!esters from dithio! and trithiocarbenium salts 745[92[2[0[4 Trithio!ortho!esters from dithioacetals 745[92[2[0[5 Trithio!ortho!formates from trithiocarbonates 765[92[2[0[6 Trithio!ortho!formates from tetrathio!ortho!carbonates 76

5[92[2[1 Preparation of Trithio!ortho!esters from other Trithio!ortho!esters 775[92[2[1[0 Hi`her trithio!ortho!esters from trithioformate esters 775[92[2[1[1 Trans!esteri_cation of trithio!ortho!esters 775[92[2[1[2 Modi_cation of R0 and R1 of R0C"SR1#2 78

5[92[2[2 Methods for the Preparation of Oxidised Derivatives of Trithio!ortho!esters 895[92[2[2[0 Oxidised trithio!ortho!esters containin` at least one sulfoxide `roup 895[92[2[2[1 Oxidised trithio!ortho!esters containin` at least one sulfone `roup 895[92[2[2[2 Oxidised trithio!ortho!esters containin` at least one sulfonate `roup 80

5[92[3 FUNCTIONS BEARING THREE SELENIUM ATOMS 80

5[92[3[0 Methods for the Preparation of Triseleno!ortho!esters 815[92[3[0[0 Triseleno!ortho!esters from RC"X0#"X1#X2 815[92[3[0[1 Triseleno!ortho!esters from carboxylic acids 815[92[3[0[2 Triseleno!ortho!esters from triselenocarbenium salts 825[92[3[0[3 Triseleno!ortho!esters from diselenoacetals and related compounds 825[92[3[0[4 Triseleno!ortho!formates from tetraseleno!ortho!carbonates 825[92[3[0[5 Hi`her triseleno!ortho!esters from triseleno!ortho!formate esters 83

5[92[4 MIXED CHALCOGEN FUNCTIONS INCLUDING OXYGEN 84

5[92[4[0 Methods for the Preparation of Functions R0C"OR1#"OR2#SR3 845[92[4[0[0 From R0C"X0#"X1#X2 84

56

57 Three Chalco`ens

5[92[4[0[1 From monothiocarboxylic esters 855[92[4[0[2 From dioxo! and oxothiocarbenium salts 855[92[4[0[3 From monothioacetals and related compounds 865[92[4[0[4 From 1!alkoxythiophenes 86

5[92[4[1 Methods for the Preparation of Functions R0C"OR1#"SR2#SR3 865[92[4[1[0 From R0C"X0#"X1#X2 865[92[4[1[1 From dithiocarbenium salts 875[92[4[1[2 From mono! and dithioacetals and related compounds 875[92[4[1[3 Miscellaneous methods 88

5[92[4[2 Methods for the Preparation of Functions R0C"OR1#"OR2#SeR3 0995[92[4[2[0 From 1!alkoxyselenophenes 099

5[92[4[3 Methods for the Preparation of Functions R0C"OR1#"SeR2#SeR3 0995[92[4[3[0 From R0C"X0#"X1#X2 099

5[92[4[4 Methods for the Preparation of Functions R0C"OR1#"SR2#SeR3 0995[92[4[4[0 From monothioacetals and related compounds 099

5[92[5 MIXED SULFUR AND SELENIUM FUNCTIONS 090

5[92[5[0 Methods for the Preparation of Functions R0C"SR1#"SR2#SeR3 0905[92[5[0[0 From R0C"X0#"X1#X2 0905[92[5[0[1 From selenodithiocarbenium salts 0905[92[5[0[2 From dithioacetals 091

5[92[5[1 Methods for the Preparation of Functions R0C"SR1#"SeR2#SeR3 0915[92[5[1[0 From diseleno!ortho!esters 091

5[92[0 INTRODUCTION

The scope of this chapter is intended to cover the synthesis of compounds bearing the C"X#"Y#Zgroup in which each of X\ Y and Z are independently linked through O\ S\ Se and Te atoms[However\ at the time of writing no such compounds containing Te had been reported in theliterature\ so the discussion is limited to O\ S and Se containing compounds[

5[92[1 FUNCTIONS BEARING THREE OXYGEN ATOMS

Carboxylic ortho!esters contain a carbon atom bearing three alkoxy or aryloxy groups[ Closelyrelated to these are the corresponding acyloxy esters "bearing at least one RCOO group#\ peroxyesters "bearing at least one ROO group# and aminoxy esters "bearing at least one R0R1NO group#[Ortho!esters which contain one or more hydroxy groups are generally unstable and decompose tocarboxylic esters and alcohols\ though a few examples are known in which ortho!hydrogen estersare stabilised by electronic and:or ring strain e}ects ð15BSB301\ 54T1948\ 79JOC1985Ł[ Methods for thepreparation of ortho!esters and related compounds have been reviewed by Post ðB!32MI 592!90Ł\DeWolfe ðB!69MI 592!90\ 63S042Ł\ Sandler and Karo ðB!75MI 592!90Ł and Simchen ð74HOU"E4#2Ł[ Otherreviews concentrate on the reactions of ortho!esters ðB!58MI 592!90\ 75UK0792Ł\ and on their use inpolymerisation reactions ð74MI 592!90Ł[

5[92[1[0 Methods for the Preparation of Carboxylic Ortho!esters and Related Compounds

5[92[1[0[0 Ortho!esters from 0\0\0!trihaloalkanes\ a\a!dihalo ethers and a!haloacetals

Williamson and Kay reported the _rst synthesis of triethyl and tripentyl ortho!formates by reactionof the appropriate sodium alkoxide with chloroform "Equation "0## ð0743LA"81#235\ 0743PRS024Ł[ Thisprocedure has since been used to prepare a number of simple trialkyl ortho!formates ð0768CB004\21JA1853\ 22JA2740\ 53RTC008Ł[ The reaction is carried out either by adding chloroform to the alkoxide\or by adding sodium metal to a mixture of the alcohol and chloroform^ a typical procedure isdescribed in Or`anic Syntheses for the preparation of triethyl ortho!formate ð40OSC"0#147Ł[ Yieldsare generally low "29Ð34)#\ irrespective of the method used[

CHCl3 RO

OR

OR

NaOR(1)

58Three Oxy`ens

The use of ~uorodichloromethane or di~uorochloromethane in place of chloroform has beenreported to give higher yields of ortho!formates ð46JA4382\ 59JA0287Ł[ Carbon tetrachloride anddichlorodi~uoromethane have also been shown to give ortho!formates on reaction with sodiumalkoxides ð10JCS0111\ 47USP1742420Ł\ these reactions proceeding via the corresponding haloformswhich are generated in situ under the alkaline conditions[

Triaryl ortho!formates are not obtained in appreciable amounts from the reaction of activatedphenols with chloroform since the preferred pathway is that of the ReimerÐTiemann reaction^less activated phenols do give ortho!formates\ but yields are generally poor ð0771CB1574\ 13JA1989\44JA5533Ł[

The Williamson synthesis has been extended to the preparation of certain higher ortho!esters^trialkyl ortho!benzoates "0# ð31JA1414\ 49JA0550Ł and heterocyclic analogues\ for example "1#ð79LA0105Ł\ and trialkyl and triaryl ortho!esters of perhalogenated!acrylates "2# ð56CB1835\60ZOR1050Ł and !crotonates "3# ð59IZV120Ł have all been prepared from the appropriate trichloro!methyl compounds[ However\ the general utility of the method for the synthesis of ortho!esters fromtrihalomethyl compounds bearing a!hydrogen atoms is limited\ since these substrates may alsoundergo competing elimination reactions under the strongly basic reaction conditions ðB!69MI 592!90\ 63S042Ł[

Ar

OR

OR

OR

(1)

NN

S(MeO)3C C(OMe)3

(2)Cl OR

Cl OR

OR

Cl

(3)F OR

OR

OR

F

Cl

ClF

(4)

A variation of the Williamson synthesis was reported by Hill et al[ ð54JOC300Ł\ who obtainedortho!formates "4\ R�H# and ortho!benzoates "4\ R�Ph# derived from ~uorinated alcohols\ whichdo not undergo the base promoted reaction\ by the iron"III# chloride catalysed reaction of thealcohol with chloroform and a\a\a!trichlorotoluene respectively "Equation "1##[

R

Cl

Cl

Cl R

OCH2Rf

OCH2Rf

OCH2RfRf OH

, FeCl3 cat.

62–80%

(5)

(2)

Nucleophilic displacement of the halogen atoms of a\a!dihalo ethers and a!haloacetals withalkoxides also gives ortho!esters[ In these cases\ mixed ortho!esters "5#\ in which R1 and R2 aredi}erent\ may be obtained "Scheme 0# ð24CB1040\ 47JPR59\ 50CB427Ł[ The cyclic diacyloxy ester "6#was obtained from a\a!dichlorophthalide and 2!hydroxybutanoic acid "Equation "2## ð43LA"476#115Ł[

NaOR2

R1

OR3

Cl

OR3NaOR3

R1

OR2

OR3

OR3R1

OR2

Cl

Cl

(6)Scheme 1

a\a!Dihalo ethers and a!haloacetals may form as intermediates in the reactions between activated0\0!dihaloalkenes and alkoxides which yield ortho!esters^ these are discussed in Section 5[92[1[0[4[

45%

CO2HOH

, PhNMe2, 20 °CO

O

O

O

OO

OClCl

(7)

(3)

5[92[1[0[1 Ortho!esters from imidate ester salts

Imidate ester salts are transformed into ortho!esters by reaction with alcohols "Equation "3##[ Thereaction is normally carried out using imidate ester hydrochloride salts\ which are prepared by the

69 Three Chalco`ens

hydrogen chloride promoted addition of alcohols to nitriles\ and the two!step sequence "nitrile toortho!ester# is named after Pinner\ who _rst described the preparation of a series of trialkyl ortho!formates using this procedure ð0772CB241\ 0772CB0532Ł[ The method is widely applicable to thesynthesis of ortho!formic and higher aliphatic ortho!esters^ yields are generally in the 59Ð79) range\but are lower "29) or less# for aliphatic ortho!esters bearing two substituents a! and:or b! to theester function ð31JA0714\ 40JA1122Ł[ Ortho!benzoate esters may be prepared from benzimidate esterhydrochlorides\ but reported yields are low ð63S042Ł[ The procedure is normally used for thepreparation of trialkyl ortho!esters "7# in which R1 and R2 are the same\ but is also suitable for thesynthesis of mixed ortho!esters in which R1 and R2 are di}erent ð0772CB241\ 0772CB0532\ 22MI 592!90Ł[

R3OHR1

OR2

NH2 X–

R1

OR2

OR3

OR3

(8)

(4)+

The simplest procedure for the alcoholysis of an imidate ester is to allow a solution of the imidateester hydrochloride in an excess of the alcohol to stand at room temperature ð17JA405\ 24JA1379Ł[However\ reaction times can be long\ and yields are often low[ Improved procedures include heatingthe imidate ester salt with an excess of the alcohol in diethyl ether ð31JA0714\ 35JA0811Ł\ or petroleumether ð42JA2876\ 47JA2804Ł[ It is important to maintain strictly anhydrous conditions during thesealcoholysis reactions\ since the ortho!ester products are extremely prone to acid!catalysed hydrolysis[High temperatures also need to be avoided\ as imidate ester hydrochlorides decompose to alkylchlorides and the corresponding carboxamide at elevated temperatures ð40JA1122Ł[

Ortho!esters may be prepared from nitriles without isolation of the intermediate imidate estersalt[ Erickson synthesised a number of trialkyl ortho!formates in moderate yields "up to 45)# by aone!step process which involved the introduction of hydrogen chloride into a large excess of bothhydrogen cyanide and the alcohol ð44JOC0462Ł[ Later workers found that better yields were obtainedif the acidity of the reaction medium was reduced to pH 1Ð5 after initial formation of the formimidateester hydrochloride ð65JAP"K#65097901\ 79JAP"K#7972616\ 73MIP410261Ł[

Other methods for the preparation of ortho!esters which proceed via imidate ester salts have beendescribed[ A variation of the Pinner method involves the alcoholysis of O!methyl imidate salts"8^ Equation "4##\ which are prepared from amides and dimethyl sulfate ð79LA0566Ł[ Ethanolysisof imidoyl chloride salts "09\ R�Et\ Ph# produced triethyl ortho!propionate and triethyl ortho!benzoate in yields of 51) and 34) respectively\ via the corresponding O!ethylimidate ester saltsð52CB1560Ł[ Reaction of formamide with benzoyl chloride or ethyl chloroformate in the presence ofalcohols gave trialkyl ortho!formates in yields of 39Ð49) "Scheme 1# ð57LA"605#196Ł\ and mixedortho!esters\ "00# for example\ were similarly obtained by treatment of formamide with benzoylchloride in the presence of a mixture of a simple alcohol and a diol ð70MI 592!90Ł[

R1

OR2

N+ MeOSO3–

(9)

R3OHR1

OR3

OR3

OR3 (5)

R

Cl

N+ Cl–

(10)

EtOO

O

(11)

R2OHH

OR2

OR2

OR2H

O

NH2

R1COClH

NH2 Cl–

O COR1R2OH

H

NH2 Cl–

OR2

+ +

Scheme 2

60Three Oxy`ens

5[92[1[0[2 Ortho!esters from carboxylic acids and derivatives

"i# From carboxylic acids and esters

Tricyclic ortho!esters are obtained from the reaction of carboxylic acids with 1!alkyl!1!hydroxy!methyl!0\2!dihydroxypropanes "Equation "5## ð46MI 592!90\ 54NEP5301525Ł[ The method works bestfor carboxylic acids bearing electron withdrawing substituents\ and the reactions are forced tocompletion by azeotropic removal of water using benzene or xylene[ Ortho!esters derived from diolsor simple alcohols are not generally available by this method[

(6)R1

OH

O

R1

O

O

O R2H+

HOR2

OHHO

Aliphatic carboxylic esters of 2!methyl!2!hydroxymethyloxetane have been shown to rearrangesmoothly to bridged tricyclic ortho!esters in high yield on exposure to boron tri~uoride etherate attemperatures of 9>C or less "Scheme 2# ð72TL4460\ 89JCS"P0#264Ł[ The reaction is postulated to proceedvia cyclisation of the zwitterionic species "01#[

R

O

O

R

O

O

O66–91%

O

BF3•OEt2

O

O

R

OF3B

+

–

Scheme 3(12)

Formate esters react with epoxides in the presence of a catalytic amount of boron tri~uoride togive cyclic ortho!formate esters "Equation "6## ð44AG263Ł[ Acetate esters do not react with epoxidesunder these conditions[

BF3

H

O

OR1R1O

O

O R2O

R2(7)

Ethanolysis of the acetoxy p!toluenesulfonate "02# under basic conditions produced the cyclicortho!ester "03# ð32JA502Ł[ This product is formed by addition of ethoxide to the intermediatedioxocarbenium ion "04#\ which is itself formed by neighbouring group displacement of tolu!enesulfonate by the acetoxy group "Scheme 3#[ The ortho!ester "05# was formed similarly "Equation"7## ð52PCS263Ł[ Acyloxy ortho!esters were formed by a similar mechanism when acetoxyacyl chlor!ides were treated with alcohols in the presence of triethylamine "Equation "8## ð62JA3905Ł^ the useof alkyl hydroperoxides in place of alcohols produced the analogous peroxy acyloxy ortho!esters inhigh yields "69Ð099)# ð56AG"E#838Ł[ This method of ortho!ester synthesis has received considerableattention in the _eld of carbohydrate chemistry for the conversion of 0!halo!1!acyloxy carbohydratederivatives "both furanose and pyranose forms# into the corresponding ortho!esters[ Triethylamineð89LA388Ł\ 1\5!lutidine ð54CJC0807Ł\ 1\3\5!collidine ð45CB203Ł and silver"I# salts ð60CAR"08#028Ł havebeen used to catalyse the reactions of 0!halo!1!acyloxy carbohydrate derivatives with alcohols\ andamide acetals ð79MI 592!90Ł and alkoxystannanes ð65CAR"40#C02Ł have been used as alternativesources of the alkoxy group[ The exo!form of the ortho!ester product normally predominates\ andis often formed exclusively[ A representative example is illustrated in Equation "09# ð89LA388Ł[

Scheme 4

EtOH, KOAc

51%+

O

OOTs

O

O

O

O OEt

(13) (15) (14)

61 Three Chalco`ens

EtOH, KOAc

71%OAc(16)

OTs

O

OOEt (8)

ROH, Et3N

42–84%O O

Cl

O O

O

O

OR

(9)

EtOH, Me3N, C6H6

37%

O

OAc

Br

OAc

AcO

O

OAc

AcO O

O

OEt (10)

Aliphatic O!trimethylsilyl ortho!esters "07\ R�alkyl# were obtained from hydroxy esters "06# bydeprotonation using a strong base "n!butyllithium or lithium diisopropylamide# followed by reactionwith chlorotrimethylsilane "Equation "00## ð80SL059Ł[ This method is not suitable for the preparationof ortho!esters from a!branched carboxylic esters[

R

TMS-O

O

OPh

Ph

O

OR

Ph Ph

i, BunLi or LiN(Pri)2

ii, TMS-Cl 82–94%

(17) (18)

OH

Ph

Ph

(11)

"ii# From lactones

Several examples of the direct formation of ortho!esters from lactones and diols have beenreported[ Le Mahieu and Kierstead ð69TL4000Ł described the acid catalysed preparation of thesteroid ortho!esters "08\ R�H\ Br# from the corresponding lactones and 0\1!dihydroxyethane"Equation "01##\ and Tamaru et al[ ð79BCJ2576Ł prepared the carbohydrate ortho!esters "19#\ "10#and "11# similarly from 1\2\3\5!tetra!O!benzylgluconolactone and the appropriate diol in yields of66)\ 62) and 32) respectively[ A variation of this method\ which is reported to give higher yieldsof ortho!esters\ involves the trimethylsilyl tri~uoromethanesulfonate catalysed reaction betweenlactones and bis!O!trimethylsilyl!0\1!diols[ Yoshimura et al[ ð70CL264Ł prepared the ortho!esters"19#\ "10# and "11# from 1\2\3\5!tetra!O!benzylgluconolactone and the corresponding bis!O!tri!methylsilyl!0\1!diols in yields of 80)\ 78)\ and 53) respectively[ The ortho!ester "12# was obtainedin 73) yield from 2\3!dihydrocoumarin and 0\1!bis!O!trimethylsilyloxyethane ð78AJC0124Ł[

O

HO

H

H

RH

O

H

O

HO

H

H

RH

HO

O

, H+, C6H6

56–72%

HOOH

(19)

(12)

Lactones undergo Lewis acid catalysed reaction with epoxides in a similar manner to formateesters to give spirocyclic ortho!esters "Equation "02##[ Lewis acids commonly used are boron tri!~uoride\ tin"IV# chloride and antimony pentachloride[ The reaction is general\ and has been usedto prepare a number of ortho!esters[ Thus\ butyrolactone reacts with 0\1!epoxyethane\ 0\1!epoxypropane\ 0\ 1!epoxy!2!phenoxypropane\ 0\ 1!epoxy!2!"3!methoxyphenoxy#propane\ 0\ 1!epoxy!

62Three Oxy`ens

O

O

O

OBn

BnO

BnO OBn

(20)

O

O

O

OBn

BnO

BnO OBn

(21)

O

O

O

OBn

BnO

BnO OBn

(22)

OO

O

(23)

0!phenylethane and 0\1!epoxycyclohexane to give the ortho!esters "13\ R�H\ Me\ CH1OPh\CH1OC5H3OMe!p\ Ph# and "14# respectively ð48LA"512#072\ 59GEP0973622\ 71MI 592!90Ł[

Lewis acid

O

R

O O OO

OR

(13)

OO

O R

(24)

OO

O

(25)

"iii# From dithiocarboxylic esters

Dithiocarboxylic esters react with dialkoxystannanes at temperatures of 59Ð84>C to a}ord ortho!esters "Equation "03## ð65CL780Ł[ The method has been used to prepare aliphatic ortho!esters andsubstituted ortho!benzoate esters\ and reported yields "generally 59) or greater# are favourablecompared to some other methods[

Bun2Sn(OR2)2, 60–95 °C

45–98%

R1

SMe

S

R1

OR2

OR2

OR2 (14)

5[92[1[0[3 Ortho!esters from dioxocarbenium salts

Meerwein et al[ ð45CB1959Ł demonstrated that the O!alkyllactonium tetra~uoroborate salts "15\R�Me\ Et# react with alkoxides to form the cyclic ortho!esters "16\ R�Me\ Et# in high yields"Equation "04##[ Ortho!esters derived from the O!ethyl tetra~uoroborate salts of coumarin and 2\3!dihydrocoumarin have been prepared similarly ð54HOU"5#250Ł[ Alkoxides have also been added todioxolenium tetra~uoroborates "17\ R0�Me\ Ph# and to 1!phenylbenzo!0\2!dioxolium tetra~uo!roborate to give the cyclic ortho!esters "18^ Equation "05## ð59LA"521#27Ł and "29^ Equation "06##ð54AG"E#762Ł respectively[ Several further examples of the addition of alcohols to dioxolenium anddioxenium salts have been described ð56CC02\ 56JOC1529\ 56T3070Ł[

63 Three Chalco`ens

NaOR

69–85%O OOROR

ORBF4

–

(26) (27)

+ (15)

NaOR2O

O

O

OR1R1

OR2BF4–

(28) (29)

+ (16)

NaORO

O

O

OPh

Ph

ORBF4–

(30)

+ (17)

5[92[1[0[4 Ortho!esters from 0\0!dialkoxyalkenes\ 0\0!dihaloalkenes and 0!alkoxyalkynes

Alcohols and phenols add to 0\0!dialkoxyalkenes "ketene acetals# to give high yields of ortho!esters "Equation "07## ð25JA418Ł[ The reaction is catalysed by acids ð47JA0136Ł\ though ortho!estersare also formed under neutral and basic conditions ð26JA1155\ 31JA0852Ł[ This method is particularlyuseful for the preparation of hindered ortho!esters\ for example trimethyl ortho!diphenylacetateð40JA2796Ł\ trimethyl ortho!dimethoxyacetate ð55CB0781Ł and triphenyl ortho!acetate ð34JA549Ł\which are di.cult to prepare by other methods[ The procedure is also suitable for the synthesis ofmixed ortho!esters "20# in which R2 and R3 are di}erent ð25JA418\ 31JA1414\ 53JOC1662Ł^ use ofbenzaldoximes in place of alcohols or phenols gives rise to aminoxy ortho!ester derivatives "20\R3�NCHAr# ð50JOC1191Ł[

R4OHOR3

OR4

OR3

(31)R2

R1OR3

OR3R2

R1

(18)

Activated 0\0!dihaloalkenes undergo reaction with sodium alkoxides\ giving rise to ortho!esterproducts[ Thus\ ortho!ester "21\ R�Me^ X�H# was isolated in 68) yield from the reactionbetween 0\0!dichloro!1!nitroethene with sodium methoxide "Equation "08## ð67BSB582Ł\ "21\ R�Et^X�Cl# was obtained in 23) yield from 0\0\1!trichloro!1!nitroethene and sodium ethoxideð67ZOR1118Ł\ and "22# was prepared from per~uoropropene and sodium methoxide "Equation"19## ð62USP2634119Ł[ It is not known whether these reactions proceed by an additionÐeliminationmechanism via a 0\0!dialkoxyalkene intermediate\ or whether they proceed by an additionÐsub!stitution mechanism via a\a!dihaloether and a!haloacetal intermediates[

NaOR, ROH, 0 °C

34–79%

OR

OR

OR

(32)

O2N

XCl

ClO2N

X

(19)

(20)NaOMe, MeOH, 55 °C, 5 h

OMe

OMe

OMe

(33)

F3C

FF

FF3C

F

In a reaction related to the addition of alcohols to 0\0!dialkoxyalkenes\ mixed ortho!acetate estershave been prepared by the Lewis acid catalysed addition of alcohols and phenols to 0!ethoxyethyne"Equation "10## ð64RTC198Ł[ Zinc chloride is the preferred catalyst for the reaction with alcohols\whereas mercury"II# acetate is preferred for phenols[ Triethyl ortho!acetate has also been obtainedby treatment of 0!ethoxyethyne with ethanolic sodium ethoxide ð42MI 592!90Ł[ Addition of oximesto 0!ethoxyethyne a}orded the mixed ortho!ester derivatives "23\ R�NCR0R1# ð59RTC777Ł[

64Three Oxy`ens

(21)ROH, ZnCl2 or ArOH, Hg(OAc)2

35–79%

OEt

OR (Ar)

OR (Ar)

(34)

OEt

Tris"b!alkoxyalkyl# ortho!acetates have been obtained by treatment of 0\0!dichloroethene withthe appropriate sodium alkoxide ð53JOC1662Ł[ It has been proposed that these reactions proceedthrough a series of elimination and addition steps via a 0!alkoxyalkyne intermediate "Scheme 4#[

NaOR

41–57%

OR

OR

OROR

OR

ClCl

Cl

Cl

NaORNaORNaOR

Scheme 5

0\0!Dialkoxyalkenes undergo zinc chloride promoted reactions with epoxides to give cyclic ortho!esters "Equation "11## ð68TL1814Ł[ The epoxide generally undergoes attack at the least hinderedposition\ unless attack at the more substituted position is favoured on electronic grounds[

O

R3OR2

OR2R1 O OR2

OR2

R1

R3ZnCl2 40–60%

(22)

Triethyl ortho!cinnamate esters have been prepared by addition of ethanol to diethoxyethen!ylidinetriphenylphosphorane "24#\ followed by a Wittig reaction of the resulting phosphorane witharomatic aldehydes ð75S286Ł "Scheme 5#[ A related method for the preparation of a series ofunsaturated cyclic ortho!esters "25# involves the addition of an enolised 0\1!diketone to phosphorane"24#\ followed by intramolecular Wittig cyclisation of the intermediate ketophosphorane "Scheme6# ð72CB0352\ 72CB2371\ 77T4984Ł[

Ph3POEt

Ph3POEt

Ar OEtOEt OEtOEt

OEtOEt

EtOH

90%

ArCHO

42–67%

– –++

(35)Scheme 6

(35)

46–71%R1 R3

O R2

OHO

O

R3

PPh3R1

O OEt

OEt

R1

R2

R3

R2

OEt

OEt

(36)

+

Scheme 7

–

The preparation of cyclic ortho!esters by thermal ð3¦1Ł cycloaddition reactions of 0\0!dialkoxyalkenes and a\b!unsaturated carbonyl compounds was _rst described by McElvain et al["Equation "12## ð43JA4625Ł[ Many further examples of ortho!esters "26# have since been preparedby reaction of 0\0!dimethoxyethene\ 0\0!dimethoxy!0!propene\ 0\0!dimethoxy!1!methyl!0!propene\0\0\1!trimethoxyethene\ 0\0\1\1!tetramethoxyethene and 1!chloro!0\0!dimethoxyethene with a rangeof substituted a\b!unsaturated carbonyl compounds ð44JA4590\ 60CC272\ 61CC752\ 70RTC02Ł[ 0\0!Dial!koxyalkenes also undergo ð1¦1Ł cycloaddition reactions with electron de_cient carbonylcompounds\ such as acyl cyanides and aldehydes\ giving rise to the cyclic ortho!esters "27# "Equation"13## ð65JCS"P0#0937\ 66JOC2017Ł[ It has been shown that ð1¦1Ł cycloadducts are the products of thelow temperature reaction between 0\0!dialkoxyalkenes and a\b!unsaturated carbonyl compounds\and that this process is reversible at higher temperature\ when formation of the ð3¦1Ł cycloadductsis favoured on thermodynamic grounds ð70RTC02Ł[

65 Three Chalco`ens

O

R4

R1O

R3

OR1

R2

O

R5

R6

R7 R7

R6

R4R5

R2

R3

OR1

OR1

heat(23)

(37)

25–90%R1O

R3

OR1

R2

(38)

O

R4 R5

O

OR1OR1

R2R3R4

R5

(24)

A number of _ve!membered ring ortho!esters have been prepared by ð2¦1Ł cycloaddition reac!tions of 0\2!dipoles to 0\0!dialkoxyalkenes[ Some examples are given in Equations "14# ð75JMC442Ł\"15# ð48G0400Ł and "16# ð55G264Ł[

MeCOCHN2, Cu(acac)3, C6H6, 85 °C, 30 min

65%

PhOMe

O OMe

OMe

Ph

OMe(25)

ButCNO, 80 °C

30%

PhOMe

NO OMe

OMe

Ph

OMe

But

(26)

125 °C, 16 h84%

OEt

NO OEt

OEtOEt

p-ClC6H4NPh

OCl

(27)

Ph

–

+

5[92[1[0[5 Ortho!esters from 0\0!dialkoxycyclopropanes and related compounds

Alcohols add to 0\0!dialkoxycyclopropanes which bear an electron withdrawing group "EWG#"carboxylic ester or sulfone# at the 1!position to give ortho!esters "Equation "17## ð62JOC0250\ 74S651Ł[Mixed ortho!esters "28#\ in which R0 and R3 are di}erent\ have been prepared by this method\ whichis analogous to the addition of alcohols to 0\0!dialkoxyalkenes[ Examples of ortho!esters preparedusing this procedure are listed in Table 0[

OR1

OR1

R2 R3

EWG OR1

R2 R3OR4

OR1

EWG

R4OH, heat

65–78%

(39)

(28)

Ring opening of 0\0!dialkoxy!1\1!dichlorocyclopropanes with potassium t!butoxide isaccompanied by elimination to produce alkynyl ortho!esters "Equation "18## ð48JA1468Ł[ Additionof alcohols to 0\0!dimethoxycyclopropene produces the unsaturated ortho!esters "39\ R�Me\ Et\Prn\ Pri\ But^ Equation "29## ð66JOC568Ł[

KOBut

OR1

OR1

R2

R2

OBut

OR1

OR1 (29)

Cl Cl

66Three Oxy`ens

Table 0 Ortho!esters "28# prepared from 0\0!dialkoxypropanes[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

YieldR0 R1 R2 R3 EWG ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐMe H H Me CO1Et 62 74S651Et H H Et CO1Et 69 74S651Me Me H Me CO1Et 61 74S651Et Me H Et CO1Et 65 74S651Me Et H Me CO1Et 67 74S651Me Ph H Me CO1Et 56 74S651Me Me Me Me CO1Et 55 74S651Me Me Me Me SO1Ph 54 62JOC0250Et Me Me Et SO1Ph 60 62JOC0250Et Me Me Me SO1Ph 62JOC0250*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

(40)

ROH

OMe

OMe

OR

OMeOMe (30)

Alcohols also add to 1\1!dialkoxyaziridines and 1\1!dialkoxy!1H!azirines to give a!amino!and a!imino!ortho!esters "30^ Equation "20## ð58TL1112\ 62JMC867Ł and "31^ Equation "21## ð56JA4613Łrespectively[ These compounds are di.cult to prepare by other methods[

(41)

R1OH

NH

OR1

OR1

R2

OR1

OR1

OR1R2

NH2

(31)

(42)

PriOH

NOR1

OR1

R2

OPri

OR1

OR1R2

NH

(32)

5[92[1[0[6 Ortho!esters from acetals

Some acetals undergo electrochemical oxidation in the presence of methanol to give ortho!estersin reasonable yields "Equation "22##[ The reaction has been shown to be successful for 1!alkyl!0\2!dioxolanes ð67S172Ł\ 1!alkyl! and 1!aryl!0\2!benzodioxoles ð74S20Ł and dimethyl acetals ofbenzaldehydes ð75T442Ł[ Dimethyl acetals of simple aliphatic aldehydes gave lower yields of ortho!esters\ and the reaction failed completely for the corresponding diethyl acetals ð67S172Ł[ Table 1lists some representative examples of ortho!esters "32# prepared by this method[

–2e–(anode), MeOHR1

OR2

OR2

R1

OR2

OMe

OR3

(43)

(33)

5[92[1[0[7 Ortho!esters from ortho!carbonate esters and trialkoxyacetonitriles

Trialkyl ortho!benzoates have been reported to be formed in up to 66) yield by treatment ofthe appropriate tetraalkyl ortho!carbonate ester with phenylmagnesium bromide "Equation "23##ð94CB450\ B!32MI 592!90Ł\ and similar syntheses of triethyl ortho!phenylpropiolate ð00BSF0297Ł andtriethyl ortho!2!butynoate ð69AG"E#345Ł have been described[ However\ the reaction is not alwayssuccessful\ and other workers have isolated only ketals and ethers from reactions of ortho!carbonateesters with Grignard reagents ð31JA0714\ 38MI 592!90Ł[ No systematic survey of this method has been

67 Three Chalco`ens

Table 1 Examples of ortho!esters "32# prepared by electro!chemical oxidation of acetals[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐYield

R0 R1 R2 ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐH 0"CH1#10 33 67S172H 0C5H30 38 74S20Me 0"CH1#10 53 67S172Me 0C5H30 41 74S20Pri

0"CH1#10 43 67S172Pri

0C5H30 50 74S20But

0"CH1#10 10 67S172But

0C5H30 58 74S20Ph 0C5H30 49 74S20Ph Me Me 89 75T4423!ClC5H3 0C5H30 37 74S203!ClC5H3 Me Me 73 75T4423!MeOC5H3 0C5H30 33 74S203!MeOC5H3 Me Me 73 75T442*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

carried out\ though DeWolfe ð63S042Ł has suggested that the Grignard reagent needs to bear anelectron withdrawing organic moiety for the reaction to work successfully[

(34)Ph

OR

OR

ORRO

OR

OR

ORPhMgBr

77%

More recently\ it was reported that trialkyl ortho!benzoate esters are obtained from the reactionsof Grignard reagents with trialkoxyacetonitriles "Equation "24## ð70S279Ł[ Trimethyl ortho!benzoate\trimethyl 1!methyl!ortho!benzoate and triethyl 1!5!di~uoro!ortho!benzoate were prepared in yieldsof 73)\ 53) and 19) respectively[ Triethyl ortho!phenylpropiolate was prepared in 53) yieldfrom phenylethynyl magnesium bromide and triethoxyacetonitrile using this method ð70S279Ł[

(35)Ar

OR

OR

ORNC

OR

OR

ORArMgX

20–84%

5[92[1[1 Preparation of Carboxylic Ortho!Esters from Other Ortho!Esters

5[92[1[1[0 Trans!esteri_cation reactions

Ortho!formate esters undergo exchange reactions on treatment with alcohols "Scheme 7#[ Thereaction\ which is acid catalysed\ can be forced to completion by distilling out R0OH "preferablymethanol or ethanol# as it is formed\ and a number of trialkyl ortho!formates derived from higheralcohols\ including functionalised alcohols such as 1!chloroethanol and 0!chloro!1!propanol\ havebeen prepared by this method ð41JA443\ 44JA2790\ 69CB528Ł[ The reaction is subject to stericconstraints\ proceeding readily with primary alcohols and less readily with secondary alcohols[Trans!esteri_cation with tertiary alcohols does not proceed to completion^ treatment of triethylortho!formate with t!butanol gave a mixture of t!butyldiethyl and di!t!butylethyl ortho!formatesð52PIA"A#34Ł[ Relatively little has been published on the trans!esteri_cation reactions of higher ortho!esters\ though work that has been reported suggests that these proceed in much the same way as forortho!formate esters ð49DOK"69#120\ 45ACS0995\ 69CB528Ł[

R2OHR1O

OR1

OR1

R2OHR2O

OR1

OR1

R2OHR2O

OR2

OR1

R2O

OR2

OR2

Scheme 8

The preparation of mixed ortho!esters by exchange reactions of trialkyl ortho!esters with simplealcohols is not usually feasible since equilibration reactions lead to all possible ortho!ester products

68Three Oxy`ens

ð22JA2740Ł[ Among the few reported exceptions to this general trend are the reactions of ortho!esterswith phenol^ treatment of triethyl ortho!formate and triethyl ortho!acetate with one equivalent ofphenol produced good yields of the diethylphenyl ortho!esters "33\ R�H\ Me#\ and reaction oftriethyl ortho!formate with two equivalents of phenol gave a reasonable yield of the ethyldiphenylortho!ester "34^ Scheme 8# ð45ACS0995\ 69CB532Ł[ A recently reported trans!esteri_cation route tomixed ortho!esters\ which is potentially general\ involves the magnesium chloride catalysed exchangereaction with alcohols "Equation "25## ð77TL1912Ł[ Mixed ortho!esters have also been obtained fromthe O!acyl derivative "35# ð58RTC786Ł\ which was itself prepared by treatment of triethyl ortho!formate with one equivalent of acetic formic anhydride "Scheme 09# ð55RTC682Ł[ In contrast to theirreactions with alcohols\ ortho!esters react cleanly with peroxides to form monoperoxy ortho!esterderivatives in high yield ð47CB0831Ł[

Scheme 9

2 equiv. PhOH, heat

(R = H)51%

EtO

OPh

OPh

1 equiv. PhOH, heat

67–92%R

OEt

OEt

R

OEt

OPh

OEt OEt

(44)(45)

R2OH, MgCl2, CH2Cl2

56–96%R1

OEt

OEtR1

OR2

OEt

OEt OEt (36)

HCO2COMe

62%EtO

OEt

OEt

AcO

OEt

OEt

ROH, Et3N

48–86%RO

OEt

OEt(46)

Scheme 10

Trans!esteri_cation of simple trialkyl ortho!esters with aliphatic 0\1! and 0\2!diols proceeds cleanlyto give mixed cyclic ortho!esters in high yields "Equation "26##[ The reaction is catalysed by acidssuch as sulfuric acid ð47CB549Ł\ p!toluenesulfonic acid ð69JA473Ł and benzoic acid ð62JA167Ł[ Trans!esteri_cation reactions of trialkyl ortho!benzoates with benzene!0\1!diol proceed in the absence ofa catalyst ð54AG"E#762Ł[ Treatment of trialkyl ortho!esters with b!hydroxycarboxylic acids yieldscyclic acyloxy ortho!esters "36# ð58TL0936\ 76HCA0219Ł[ In contrast to the equilibration reactionsbetween simple trialkyl ortho!esters and alcohols\ the cyclic ortho!ester "00# reacts moderately cleanlywith alcohols to give the exchanged products "37# in yields of 30Ð47) "Equation "27## ð79JCS"P0#645Ł[

R1

OR2

OR2

O

OOR2

R2O

R1

OHHO(37)

O

O

R4

R4

R3

R2O

R1

O(47)

(38)OEtROH, H+

41–58%

O

OOR

O

O(11) (48)

Trialkyl ortho!esters react with conformationally ~exible triols such as glycerol\ 0\2!dihydroxy!1!hydroxymethyl!1!methylpropane and 0\1\3!trihydroxybutane to give good yields of the cor!responding tricyclic ortho!esters "38#\ "49# and "40# respectively ð79MM141\ 79CC196\ 77JA3033Ł\ andexchange with all cis!0\2\4!trihydroxycyclohexane gives high yields of polycyclic ortho!esters "41#

79 Three Chalco`ens

ð42CB689\ 43CB194Ł[ Trans!esteri_cation with conformationally restricted triols normally gives prod!ucts arising from exchange of only two of the alkoxy groups of the ortho!ester[ For example\exchange with 1\2\4!trihydroxy nucleoside analogues generally leads to exclusive formation of theortho!ester derived from the 1\2!dihydroxy unit of the triol "Equation "28## ð53CI"L#470\ 56CCC2953\74S397Ł[ The trans!esteri_cation method has been used for the preparation of many cyclic\ bicyclicand tricyclic ortho!esters from dihydroxy! and trihydroxy!carbohydrate\ nucleoside and steroidderivatives ðB!69MI 592!90\ 66USP3910348\ 77EUP159868Ł[

(49)

O

O

R O

(50)

O

O

R O

(51)O

O

R O

(52)

O OO

R

R1C(OR2)3

O HetHOH2C

OHHO

O HetHOH2C

O O

R1 OR2

(39)

Ortho!esters have also been prepared by the alcoholysis of amide acetals ð70JOC775Ł and trithio!ortho!esters ð37JA1157\ 79JOC639Ł[

5[92[1[1[1 Modi_cation of R0 and R1 of R0C"OR1#2

Ortho!esters bearing a!hydrogen atoms react with one equivalent of bromine to give a!bromoortho!esters "42# in up to 79) yield ð26JA0162\ 31JA1414\ 35JA0811Ł^ use of two equivalents of brominegives a\a!dibromo ortho!esters ð31JA0852Ł[ Dehydrobromination of a!bromo ortho!esters\ "e[g[\ "43##\to unsaturated ortho!esters\ "e[g[\ "44##\ has been achieved\ but yields are low "08Ð21)# ð62S196\74JAP"K#59197872Ł[ Reaction of triethyl ortho!acetate with tri~uoromethylselenenyl chloride gavetriethyl a!"tri~uoromethylselenenyl#ortho!acetate\ which was converted to the bis"tri~uoro!methylselenenyl# derivative by deprotonation with sodium hydride\ followed by treatment with afurther equivalent of tri~uoromethylselenenyl chloride "Scheme 00# ð81CB460Ł[ Trialkyl ortho!acetates have also been shown to react with perhalogenated aldehydes and ketones\ producing theadducts "45\ R0�H\ CF2\ CClF1^ R1�Me\ Et^ X�F\ Cl# in yields of 74Ð83) "Equation "39##ð66ZOR832Ł[

Br

OR3

R1 R2OR3

OR3

(53) (54)

O

OO

Br

(55)

O

OO

OEt

OEt

OEtF3CSeCl, Et2O, –20 °C

87%

OEt

OEt

OEt

OEt

OEt

OEtF3CSe

F3CSe

F3CSeNaH, F3CSeCl

Et2O, –20 °C97%

Scheme 11

O

R1

X

F

FOH OR2

R1 OR2

OR2F2XC

OR2

OR2OR2

(40)85–94%

(56)

Dehydrohalogenation of tris"b!chloroalkyl# ortho!esters yielded trialkenyl ortho!esters "Equation

70Three Sulfurs

"30## ð69CB528Ł[ Ozonolysis of tris"1!propenyl# ortho!formate gave tri!O!acetyl ortho!formate "Equa!tion "31## ð69CB528Ł[

KOBut

O

O

Cl

R2

R1

Cl

R2

O

R2

Cl

O

O

R2

R1

R2

O

R2

(41)

O3, –78 °C

60%O

O

O AcO

OAc

OAc

(42)

5[92[2 FUNCTIONS BEARING THREE SULFUR ATOMS

Trithio!ortho!esters contain a carbon atom bearing three alkanethio or arenethio groups[ Relatedto these are the analogous acylthio esters "containing at least one RCOS group#\ hydrogen esters"containing at least one HS group# and oxidised derivatives bearing sulfoxide\ sulfone and sulfonylgroups[ Methods for the preparation of trithio!ortho!esters and related compounds have beenreviewed by Post ðB!32MI 592!90Ł\ DeWolfe ðB!69MI 592!90Ł and Simchen ð74HOU"E4#2Ł[

5[92[2[0 Methods for the Preparation of Trithio!ortho!esters and Related Compounds

5[92[2[0[0 Trithio!ortho!esters from RC"X0#"X1#X2

"i# From 0\0\0!trihaloalkanes and a\a!dihalo ethers

Gabriel reported the _rst synthesis of triethyl trithio!ortho!formate and triphenyl trithio!ortho!formate by reaction of the appropriate thiolate salt with chloroform "Equation "32## ð0766CB074Ł[This method has since been used to prepare a range of trialkyl and triaryl trithio!ortho!formateesters ð0767CB1154\ 22RTC326\ 53CR"148#3940Ł^ yields from reactions with arenethiols are usually high"69) or greater#\ but are lower from reactions with aliphatic thiols[ Bromoform and chloro!di~uoromethane also react with sodium arenethiolate salts to give high yields of triaryl trithio!ortho!esters ð45JA368\ 59JA5007Ł[ Carbon tetrachloride reacts with alkanethiolates to give trialkyltrithio!ortho!esters\ the reactions proceeding via formation of chloroform under the alkaline reactionconditions ð22RTC326Ł[ Tris"tri~uoromethyl# trithio!ortho!formate "46# was prepared by reaction ofiodoform with Hg"SCF2#1 "Equation "33## ð56JOC1952Ł[

M+ –SRRS

SR

SR

CHCl3 (43)

Hg(SCF3)2, 130 °CF3CS

SCF3

SCF3

CHI3

(57)

(44)

Relatively few reports of the preparation of higher trithio!ortho!esters from 0\0\0!trihaloalkaneshave appeared[ 1!Trichloromethylbenzimidazole was converted to the trithio!ortho!esters "47\R�Me\ p!ClC5H3# by reaction with the corresponding thiol ð56JCS"C#29Ł\ and the activated tri!~uoromethyl group of the thiazole "48# underwent reaction with methanethiol to give the trithio!

71 Three Chalco`ens

ortho!ester "59# ð80JHC0902Ł[ A series of a\a\a!trihalotoluenes have been converted to tris"tri~uoromethyl# trithio!ortho!benzoate esters "50# by treatment with AgSCF2 ð58ZOB0644Ł[

NH

N SR

SR

SR

(58)

N

S

CF3

NH

NEt2Cl

O

(59)

N

S

C(SMe)3

NH

NEt2Cl

O

(60)

Ar

SCF3

SCF3

SCF3

(61)

Trithio!ortho!formate esters may also be prepared from dichloromethyl alkyl ethers^ treatmentwith lead"II# alkanethiolates gives trialkyl trithio!ortho!formates ð50CB427Ł\ whereas reaction witharenethiols in the presence of zinc produces triaryl trithio!ortho!formates ð60ZOR0776Ł "Scheme 01#[

R1O

Cl

Cl

SR2

SR2

SR2

ArS

SAr

SAr

Pb(SR2)2, Et2O

ArSH, Zn, Et2O, 35 °C

66–92%

Scheme 12

"ii# From a!halodithioacetals and a!acyloxy! and a!alkoxydithioacetals

Treatment of chlorobis"methanethio#methane with methanethiol produced trimethyl trithio!ortho!formate\ though reaction with higher alkanethiols was accompanied by disproportionation\giving rise to mixtures of trithio!ortho!esters ð50LA"537#10Ł[ Cyclic a!chlorodithioacetals "51\ X�S\CH1# reacted with benzenethiol to give high yields of the trithio!ortho!esters "52\ X�S\ CH1^Equation "34## ð65BCJ442Ł[ Reaction of the benzoyloxytrithiane "53# with a range of alkane! andarene!thiols produced the trithio!ortho!esters "54\ R�alkyl\ aryl^ Equation "35## ð63BCJ1346\64BCJ1385Ł[ The 1!alkoxybenzodithiole "55# reacted similarly with ethanethiol in the presence ofacetic acid to give 1!ethylthio!0\2!benzodithiole "Equation "36## ð64S325Ł[

PhSH, C6H6, RT

80–90% S

S

X SPh

S

S

X Cl

(62) (63)

(45)

(46)RSH

S

S

S SR

S

S

S OCOPh

(64) (65)

EtSH, AcOH, 20 C, 5 h

84%S

SO

S

SSEt

(66)

(47)

"iii# From carboxylic ortho!esters and related compounds

Carboxylic ortho!formate esters undergo exchange reactions with alkanethiols and arenethiols togive trithio!ortho!esters "Equation "37##[ The reaction may be catalysed using hydrogen chlorideð56AG"E#331Ł\ p!toluenesulfonic acid ð44JA498Ł\ zinc chloride ð53T306Ł\ boron tri~uoride etherateð61CB2179Ł and montmorillonite KSF ð78SC20Ł\ though it will often proceed in the absence of a

72Three Sulfurs

catalyst ð59IZV0890Ł[ Exchange of trialkyl ortho!formates with ethanedithiol and propanedithiolgave "56# and "57# respectively ð15JCS1152\ 56AG"E#331Ł\ and exchange of triethyl ortho!formate with1!methyl!1!thiohydroxymethylpropane!0\2!dithiol produced the tricyclic trithio!ortho!ester "58\R�H# ð44JA498Ł[ Little work has been reported on the exchange of higher ortho!esters with thiols\though triethyl ortho!acetate does undergo reaction with 1!methyl!1!thiohydroxymethylpropane!0\2!dithiol to give the tricyclic trithio!ortho!ester "58\ R�Me# ð44JA498Ł[

R2SHR1O

OR1

OR1

R2S

SR2

SR2

(48)

SS

S

S

S

S

(67)

S S

(68)

S

SS

S

(69)

S

S

R S

5[92[2[0[1 Trithio!ortho!esters from thioimidate ester salts

Thioimidate ester hydrochloride salts react with alkanethiols and arenethiols to yield the trithio!ortho!esters "69# ð42JA0557\ 51JOC1747Ł[ Although this method is analogous to the widely used Pinnersynthesis of ortho!esters\ relatively few reports of the preparation of trithio!ortho!esters using thisprocedure have appeared[ Some trithio!ortho!esters prepared by this method are listed in Table 2[

R3SHR1

SR2

NH2 Cl–R1

SR3

SR3

SR3

(70)

+(49)

Table 2 Trithio!ortho!esters "69# pre!pared from thioimidate ester hydro!

chloride salts[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR0 R2 Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐH Ph 42JA0557C1F4 Me 51JOC1747C2F6 Me 51JOC1747C2F6 Et 51JOC1747*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Other methods for the preparation of trithio!ortho!esters which proceed via thioimidate inter!mediates have been described[ Formamide undergoes an acid catalysed reaction with thiols togive trithio!ortho!esters "Scheme 02# ð96CB0639\ 96LA"242#020Ł\ and the formanilide "60# reacts withphosphorus oxychloride in the presence of thiols to give trithio!ortho!esters in yields of 33Ð58)"Scheme 03# ð59IZV0717Ł[ Acetamide derivatives do not react under similar conditions ð48RTC243Ł[

RSHH

O

NH2

H

SR

NH

RSHRS

SR

SR

Scheme 13

H

O

N

Me

PhH

Cl

N

Me

Ph Cl–H

SR

N

Me

Ph Cl–RS

SR

SR

Scheme 14

+ +44–69%

(71)

73 Three Chalco`ens

5[92[2[0[2 Trithio!ortho!esters from carboxylic acids and derivatives

"i# From acyl chlorides and anhydrides

A general method for the preparation of trithio!ortho!esters involves the treatment of acylchlorides with thiols in the presence of zinc chloride or aluminium trichloride "Equation "49##[ Thisprocedure has been used to prepare a range of trithio!ortho!esters derived from aliphatic ð48RTC243Łand aromatic ð42JA0557\ 79JOC639\ 75TL3750Ł acyl chlorides^ yields are usually greater than 39)[ Alimitation of the method is that acyl chlorides containing one or more a!hydrogen atoms give pooryields of trithio!ortho!esters due to competing elimination reactions\ though this problem can beovercome to some extent by using an excess of the thiol reagent ð48RTC243Ł[ Reaction of aceticanhydride with 2!methylbenzenethiol in the presence of boron tri~uoride has been reported to givetris"2!methylphenyl# trithio!ortho!actetate in 29) yield ð42JA0557Ł[

R2SH, ZnCl2 or AlCl3, heatR1

O

ClR1

SR2

SR2

SR2 (50)

"ii# From carboxylic esters and thioesters

In 0896\ Holmberg ð96CB0639\ 96LA"242#020Ł discovered that formate esters undergo an acid pro!moted reaction with alkanethiols and arenethiols to give trithio!ortho!esters "Equation "40##[ Arange of trialkyl and triaryl trithio!ortho!formates have been prepared using this method ð96CB0639\96LA"242#020\ 37JCS576\ 51RTC0998Ł[ These reactions simply involve saturating a mixture of the esterand thiol with hydrogen chloride\ and allowing the mixture to stand^ yields are normally greaterthan 49)[ Triaryl ortho!formates have also been obtained from the reactions of arenethiomagnesiumbromides with ethyl formate ð51ZOB634Ł[

R2SH, HClH

O

OR1R2S

SR2

SR2

(51)

The Holmberg method is not suitable for the preparation of trithio!ortho!esters from highercarboxylic esters[ In a modi_cation of the reaction\ triethyl trithio!ortho!acetate has been obtainedin low yield from the zinc chloride catalysed reaction of ethanethiol with ethyl acetate ð48RTC243Ł[More recently\ the synthesis of trialkyl trithio!ortho!benzoate esters by the aluminum trichloridecatalysed reaction of methyl benzoates with alkanethiotrimethylsilanes has been reported "Equation"41## ð79JOC639\ 75TL3750Ł[

RS-TMS, AlCl3Ar

O

OMeAr

SR

SR

SR (52)

Thiocarboxylic esters "61\ R0�H\ alkyl\ aryl# undergo acid or Lewis acid catalysed reactionswith thiols to give trithio!ortho!esters ð34USP1278042\ 42JA0557\ 64JOC852Ł[ Mixed trithio!ortho!esters"62#\ in which R1 and R2 are di}erent\ may be prepared by this method "Equation "42## ð34USP1278042\42JA0557Ł[

R3SH

HCl or ZnCl2 or BF3

R1

O

SR2R1

SR2

SR3

SR3

(72) (73)

(53)

"iii# From carboxylic acids

Formic acid reacts with alkanethiols and arenethiols to give trithio!ortho!formate esters ð00CB2124\01CB1831Ł[ Higher carboxylic acids do not generally undergo this reaction^ exceptions are thereactions of tri~uoroacetic acid with ethane!0\1!dithiol and propane!0\2!dithiol\ which give the

74Three Sulfurs

cyclic bistrithio!ortho!esters "63# and "64# respectively ð56CC0978\ 57JOC1493Ł[ Reaction of formicacid with hydrogen sul_de and acetic anhydride in the presence of zinc chloride a}orded tris"acetylthio#methane "65^ Equation "43## in 39) yield ð65CS011Ł[ This compound may also beprepared by treatment of formic acid with thioacetic acid and acetic anhydride in the presence ofzinc chloride ð65CS011Ł[

SS

(74)

S

S

S

SCF3

CF3 S S

S

SS

S

CF3 CF3

(75)

AcS

SAc

SAc

H2S, (MeCO)2O, ZnCl2, MeCO2H, 20–50 °C, 2 h

40%HCO2H (54)

(76)

5[92[2[0[3 Trithio!ortho!esters from dithio! and trithiocarbenium salts

Trithio!ortho!esters and related compounds are obtained from the addition of thiols and othersulfur nucleophiles to dithiocarbenium salts[ Reaction of the dithiolium tetra~uoroborate salt"66# with sodium benzenethiolate produced the 1!phenylthio!0\2!dithiole "67^ Equation "44##\ andreaction with N\N!dialkyldithiocarbamate salts gave 1!dithiocarbamoyldithioles "68# ð58CPB0820Ł[Treatment of the dithiolium perchlorate salt "79# with one equivalent of potassium ethyl xanthateyielded the analogous ethoxythiocarbonythio derivative "70#\ whereas the use of an excess ofpotassium ethyl xanthate produced the sul_de "71#\ the reaction being thought to proceed via furtherreaction of "70# with the xanthate "Scheme 04# ð66JOC0432Ł[

NaSPh, EtOH, 78 °C, 1 h

66%

(77) (78)

S

SPh SPh

S

SPh+ BF4

– (55)

(79)

S

SPh SCSNR1R2

(80)

S

SPh+ ClO4

–

(81)

S

SPh SCSOEt

S

SPh S–

S

S

EtO

S SCSOEtPh S–(81)

–EtOCSSCSOEt(80)EtOCS2K

S

S

S

S SPhPh

(82)Scheme 15

1!Methanethio!0\2!dithiolium salts may be reduced to 1!methanethio!0\2!dithioles using sodiumborohydride[ The dithiole "73# was prepared in 67) yield from the salt "72# by this method "Equation"45## ð81JOC0585Ł[

NaBH4, MeCN, 20 °C, 1 h

(83) (84)

S

SSMe BF4

–

MeSe

MeSe

+

S

SSMe

MeSe

MeSe

(56)

5[92[2[0[4 Trithio!ortho!esters from dithioacetals

Dithioacetals may be converted into trithio!ortho!esters by deprotonation with a strong base\followed by reaction of the metallated species "74# with a disul_de "Scheme 05#[ The reaction was

75 Three Chalco`ens

_rst described by Frohling and Arens ð51RTC0998Ł\ who prepared triethyl trithio!ortho!benzoate in65) yield from benzaldehyde diethyl dithioacetal using sodium amide and diethyl disul_de "Equa!tion "46##[ A procedure for the preparation of trithio!ortho!ester "75# from the cyclic dithioacetal"76# using n!butyl lithium and dimethyl disul_de is given in Or`anic Syntheses ð66OS"45#7Ł\ and thismethod has also been used for the preparation of a range of benzoic\ cinnamic and aliphatic trithio!ortho!esters ð61JOC1646Ł[ However\ the reaction may not be general for the preparation of aliphatictrithio!ortho!esters*trithioacetates and trithiopropionates could not be prepared from the cor!responding dithioacetals using sodium amide and dialkyl disul_des\ presumably because of com!peting elimination reactions ð51RTC0998Ł[ The preparation of trithio!ortho!formate esters by thismethod appears to be dependent on the nature of the substituents on sulfur\ and on the base used[Seebach et al[ prepared the mixed trithio!ortho!formate ester "77# in 84) yield from bis"ben!zenethio#methane using n!butyllithium and dimethyl disul_de "Equation "47## ð61CB2179Ł\ whereasFrohling and Arens obtained only tetraethyl tetrathio!ortho!carbonate from the reaction of thebis"ethanethio#methane with sodium amide and diethyl disul_de "Scheme 06# ð51RTC0998Ł[ Doubly02C!labelled trimethyl trithio!ortho!formate has been prepared by a related method\ in which thelithiated dithioacetal "78# is treated sequentially with elemental sulfur followed by 02C!labelledmethyl iodide "Scheme 07# ð73HCA0969Ł[

M+B– R3SSR3

R1

SR2

SR2

R1

SR2

SR2

R1

SR2

SR3

SR2M+–

(85)Scheme 16

i, NaNH2

ii, EtSSEt 76%

Ph

SEt

SEt

SEtPh

SEt

SEt

(57)

S

SMeS

Ph

(86)

S

S

(87)

Ph

(58) i, BunLi

ii, MeSSMe 95%

MeS

SPh

SPh

SPh

SPh(88)

NaNH2, EtSSEtEtS

SEt

SEt

SEt

SEt

EtS

SEt

SEt

NaNH2, EtSSEtSEt

Scheme 17

i, BunLi

ii, 1/8 S8

H

SMe

S– Li+

SMe

SMe

H

SMe

SMe

Me*I

58%SMeSMe* *Li+ – *

(89)

Scheme 18

*

76Three Sulfurs

Trithio!ortho!formates have been prepared by reaction of N!p!toluenesulfonylsul_limines "89#derived from dithioacetals of formaldehyde with alkanethiols and arenethiols under alkaline con!ditions "Equation "48## ð65S440Ł[ Mixed trithio!ortho!esters are available by this method[

R3SH, KOH

61–82%R1S

SR2

SR3S R2

SR1

TosN(90)

(59)

5[92[2[0[5 Trithio!ortho!formates from trithiocarbonates

Addition of phenyllithium to diphenyl trithiocarbonate at −67>C yields the triphenyl!thiomethylide anion "80^ Equation "59##[ This anion\ when prepared by a di}erent method\ hasbeen quenched with deuterated water to give the deuterated triphenyl trithio!ortho!formate "81#ð61CB376Ł[ Similar addition of methyllithium to the dithiolone "82#\ followed by quenching withacetic acid\ yielded the 1!methanethio!0\2!dithiole "83^ Scheme 08# ð76TL3042Ł[ The use of lithiatedtrithio!ortho!formates for the preparation of higher trithio!ortho!esters is discussed in Section5[92[2[1[0[

PhSLi, THF, –78 °CSPh

SPhLi+ –

(91)

SPhS

PhS

PhS(60)

D

SPh

SPh

SPh

(92)

MeLi, THF, –60 °C

S

S

S

SS

S

S

S

SSMe

S

S

S

SSMe–

Li+

AcOH

75%

(93) (94)Scheme 19

Diphenyl trithiocarbonate undergoes cycloaddition reactions with diaryldiazomethanes to pro!duce the cyclic trithio!ortho!ester derivatives "84^ Equation "50## ð54CB2292Ł[

Ar2CN2

S

PhS

PhS S

SPh

SPhAr

Ar(95)

(61)

5[92[2[0[6 Trithio!ortho!formates from tetrathio!ortho!carbonates

Seebach ð56AG"E#331Ł reported the preparation of the trithio!ortho!formate "86# by treatment ofthe tetrathio!ortho!carbonate "85# with n!butyllithium at −67>C\ followed by quenching the reactionwith water "Scheme 19#[ The reaction proceeds via the lithiated trithio!ortho!formate ester "87#[Similar treatment of tetraphenyl tetrathio!ortho!carbonate with n!butyllithium gave the tri!

77 Three Chalco`ens

phenylthiomethylide anion "80#\ which has been used to prepare the deuterated trithio!ortho!formate"81# ð61CB376Ł[ The use of lithiated trithio!ortho!formates for the preparation of higher trithio!ortho!esters is discussed in Section 5[92[2[1[0[

H2O

70%S

S

SMe

SMe

S

S

S

SSMe SMe

Li+

–BunLi, THF, –78 °C

(96) (98) (97)Scheme 20

5[92[2[1 Preparation of Trithio!ortho!esters from other Trithio!ortho!esters

5[92[2[1[0 Higher trithio!ortho!esters from trithioformate esters

In 0851\ Hine et al[ ð51JA0640Ł reported the generation of the potassium trithio!ortho!formate salt"88# by deprotonation of trimethyl trithio!ortho!formate with potassium amide\ and the reaction ofthis with methyl iodide to produce trimethyl trithio!ortho!acetate in 64) yield "Scheme 10#[ Seebachet al[ ð56AG"E#331\ 61CB376\ 61CB2179Ł later described the generation of several lithiated trithio!ortho!formate esters from the appropriate trithio!ortho!formate with n!butyllithium at −67>C\ and thesubsequent reactions of these with a range of electrophiles to yield higher trithio!ortho!esters[ Thishas since developed into a general method for the homologation of trithio!ortho!formates[ Thus\lithiated trithio!ortho!formates react with alkyl halides to give aliphatic trithio!ortho!estersð56AG"E#331\ 61CB376\ 61CB2179\ 65CL32\ 71TL2396Ł\ with aldehydes and ketones to give a!hydroxy!trithio!ortho!esters ð56AG"E#331\ 61CB376\ 65CL32\ 70TL3998Ł\ with epoxides to give b!hydroxy trithio!ortho!esters ð56AG"E#331\ 61CB376Ł\ with cyclic a\b!unsaturated ketones to give g!ketotrithio!ortho!esters ð64CC105\ 78TL4370Ł\ with carbon dioxide to give trithiomono!ortho!oxalates ð56M0932Ł\ withcarbon disul_de to give trithiomono!ortho!dithiooxalates ð77T1952Ł\ with chloroformate esters togive trithiomono!ortho!oxalate esters ð56AG"E#331\ 61CB376Ł and with iodine to give coupled hexa!thiodi!ortho!oxalates ð61CB2781Ł "Scheme 11#[ An example of the acylation of a lithiated trithio!ortho!formate by reaction with a lactone has been reported "Equation "51##\ but this reaction is notgeneral ð80CJC304Ł[ Since lithiated trithio!ortho!esters may also be obtained from trithiocarbonates"Section 5[92[2[0[5# and tetrathio!ortho!carbonates "Section 5[92[2[0[6#\ these compounds shouldalso be regarded as precursors of higher trithio!ortho!esters[

MeI

75%

–KNH2, NH3

MeS

SMe

SMe

K+ MeS

SMe

SMe

SMe

SMe

SMe

(99)Scheme 21

OO

S

S

Li+ MeS

S

SOH

O SMe

– (62)

Triethyl trithio!ortho!heptanoate has been prepared by a radical homologation procedure\ involv!ing treatment of triethyl trithio!ortho!formate with 0!hexene in the presence of t!butyl hydroperoxide"Equation "52## ð77MI 592!90Ł[

1-hexene, ButO2H, 130 °C

76%EtS

SEt

SEt SEt

SEtSEt (63)

5[92[2[1[1 Trans!esteri_cation of trithio!ortho!esters

In contrast to the chemistry of ortho!esters\ relatively little work has been published on thepreparation of trithio!ortho!esters by trans!esteri_cation reactions of other trithio!ortho!esters with

78Three Sulfurs

Scheme 22

R1S

SR2

SR3

R4

SR1

SR3

SR2 SR1

SR3R5

HO

R4 SR2

SR1

SR3

SR2

OH

R4

SR1

SR3HO

O

SR2

SR1

SR3HS

S

SR2

SR1

SR3R4O

O

SR2SR1

SR3R3S

R1S

R2S SR2

O

R4

SR1

SR3

SR2 BunLi, THF, –78 °C

Li+ –

R4X R4COR5

SR1

SR3

SR2

CO2

R4OCOCl

CS2

O

I2

O

thiols[ Mixed trithio!ortho!esters undergo rapid acid catalysed disproportionation reactions to yieldmixtures of trithio!ortho!esters "Scheme 12# ð50LA"537#10Ł[ The dithiolane "099# and dithiane "090#have been prepared by heating triethyl trithio!ortho!formate with the appropriate dithiol in thepresence of zinc chloride ð77URP0310633Ł[

R1

SR2

SR3

SR3 R1

SR2

SR2

SR2 R1

SR2

SR3

SR2 R1

SR3

SR3

SR3+ +H+

Scheme 23

SEtS

S(100)

S

S

SEt

(101)

5[92[2[1[2 Modi_cation of R0 and R1 of R0C"SR1#2

Treatment of triaryl trithio!ortho!acetates with deuterated tri~uoroacetic acid in deutero!chloroform results in a rapid proton exchange reaction to give the deuterated trithio!ortho!acetates"091^ Equation "53## ð64JOC852Ł[ However\ attempts to homologate triaryl trithio!ortho!acetates byreaction with electrophilic acylating agents have not been successful ð64JOC852Ł[

CF3CO2D, CDCl3, RT, 5 min

ca. 100%

SAr

SAr

SAr D3C

SAr

SAr

SAr

(102)

(64)

Deacetylation of tris"acetylthio#methane using methanolic hydrogen chloride produced meth!anetrithiol "092^ Equation "54## in 49) yield ð65CS011Ł[ This product is stable at −29>C\ although

89 Three Chalco`ens

it polymerises slowly at 19>C[ The hydrolysis proceeds via di! and monoacetyl trithiomethaneintermediates\ which can be detected in the 0H NMR spectrum of the reaction mixture[

2% HCl in MeOH, 6 h

50%AcS

SAc

SAc

HS

SH

SH(103)

(65)

5[92[2[2 Methods for the Preparation of Oxidised Derivatives of Trithio!ortho!esters

5[92[2[2[0 Oxidised trithio!ortho!esters containing at least one sulfoxide group

Triaryl trithio!ortho!formate esters are oxidised to the triaryl sulfoxide derivatives in high yieldson treatment with peroxyacetic acid "Equation "55## ð53CR"148#3940Ł[ The sulfoxide "093# has beenprepared by oxidation of the corresponding sul_de with peroxybenzoic acid "Equation "56##ð37RTC773Ł[

MeCO3H, Et2O

>90%ArS

SAr

SAr

ArOS

SOAr

SOAr

(66)

PhCO3HMeS

SO2Me

SO2Me

MeOS

SO2Me

SO2Me(104)

(67)

5[92[2[2[1 Oxidised trithio!ortho!esters containing at least one sulfone group

Treatment of the sulfone "094# with two equivalents of N!ethanethiophthalimide in the presenceof potassium t!butoxide produced the sulfonyldithio!ortho!ester derivative "095# in high yield "Equa!tion "57## ð71CC0072Ł[ Bis"sulfonyl#methanes "096# react with alkyl thioalkyl sulfones and alkane!sulfonyl or arenesulfonyl chlorides in the presence of sodium ethoxide to give disulfonylthiomethanes"097# ð22JCS295Ł and trisulfonylmethanes "098# ð30CB0556Ł respectively "Scheme 13#[ These oxidisedtrithio!ortho!formate derivatives produce the analogous trithio!ortho!acetate derivatives on treat!ment with methyl iodide in aqueous alkali "Equation "58## ð0781CB236\ 0781CB250Ł[

SO2Me

SEt87% SEt

SO2Me

N

O

O

SEt, KOBut, DMSO

(106)

Ph

O2 equiv.

Ph

O

(105)

(68)

R3SSO2R4, NaOEt, EtOHR3S

SO2R1

SO2R2

SO2R1

SO2R2

R3SO2Cl, NaOEt, EtOHR1SO2

SO2R2

SO2R3

(108) (107) (109)Scheme 24

MeI, aq. NaOH SO2R1

SOnR3

SO2R2R1SO2

SO2R2

SOnR3

(69)

80Three Seleniums

Trisulfones "009# are the products normally obtained from the oxidation of trialkyl and triaryltrithio!ortho!formates using acidic permanganate ð0781CB236\ 22RTC326Ł\ though Laves ð0789CB0303Łhas reported that controlled oxidation of triphenyl trithio!ortho!formate using this reagent producesthe disulfone "000#[ Yields from these permanganate oxidations are often low due to the competingformation of disulfonylmethanes and sulfonic acids ð96CB0639\ 22RTC326Ł[ Trialkyl trisulfones havebeen obtained from the oxidation of trialkyl trithio!ortho!formates with peroxyacetic and mon!operoxyphthalic acids ð35RTC42\ 42LA"470#022\ 56USP2222996Ł[ The tricyclic trisulfones "001\ R�H\Me# and triaryl sulfones "002# were prepared by oxidation of the corresponding trithio!ortho!estersusing hydrogen peroxide in acetic acid ð44JA498\ 53CR"148#3940Ł[ Oxidation of disulfones "003\ R�H\Me# with alkaline permanganate or hydrogen peroxide produced the corresponding trisulfones inhigh yields "Equation "69## ð0781CB236\ 20JCS1526\ 35RTC42Ł[

RO2S

SO2R

SO2R(110)

PhS

SO2Ph

SO2Ph(111)

SO2

SO2

R SO2

(112)

ArO2S

SO2Ar

SO2Ar(113)

R1

SO2R2

SR3

(114)

SO2R2KMnO4 / HO– or H2O2

R1

SO2R2

SO2R3

SO2R2 (70)

The disulfonylthiomethane "005# was obtained in 83) yield from the sodium ethanethiolatereduction of the disulfonyldithiomethane "004^ Equation "60## ð71CC0072Ł[

EtS

SO2Et

SEt(115)

SO2EtNaSEt, THF

94%EtS

SO2Et

SO2Et(116)

(71)

5[92[2[2[2 Oxidised trithio!ortho!esters containing at least one sulfonate group

Methanetrisulfonic acid "006# has been prepared by various methods\ including sulfonation ofmethanedisulfonic acid and oxidation of thiol methanetrisulfonic acid^ these have been reviewed byBacker ð29RTC0096Ł and summarised by DeWolfe ðB!69MI 592!90Ł[ The trimethyl and triethyl esters"008\ R�Me\ Et# were obtained by treatment of the silver"I# salt "007# with methyl iodide and ethyliodide respectively "Equation "61## ð38AK"0#120\ 49ACS286Ł[

HO3S

SO3H

SO3H(117)

–O3S

SO3–

SO3–

(118)

RI, C6H6RO3S

SO3R

SO3R

(119)

3Ag+ (72)

5[92[3 FUNCTIONS BEARING THREE SELENIUM ATOMS

Triseleno!ortho!esters contain a carbon atom bearing three alkaneseleno or areneseleno groups[Methods for the preparation of triseleno!ortho!esters have been reviewed brie~y by Krief and Hevesið73MI 592!90Ł[

81 Three Chalco`ens

5[92[3[0 Methods for the Preparation of Triseleno!ortho!esters

5[92[3[0[0 Triseleno!ortho!esters from RC"X0#"X1#X2

"i# From 0\0\0!trihaloalkanes

Triseleno!ortho!formates "019\ R�Me\ Ph# have been obtained from the treatment of bromoformwith the appropriate sodium selenolate "Equation "62## ð73HCA0969\ 73S328Ł[ The sodium selenolateswere prepared by reduction of diselenides in situ^ sodium methaneselenolate was prepared by thesodium:liquid ammonia reduction of dimethyl diselenide ð73HCA0969Ł\ and sodium benzene!selenolate was prepared by reduction of diphenyl diselenide using hydrazine ð73S328Ł[ Seebachð73HCA0969Ł prepared 02C!labelled trimethyl triseleno!ortho!formate from 02C!labelled bromoformusing this method[

NaSeRRSe

SeR

SeR(120)

CHBr3 (73)

"ii# From a\a!dihalo ethers

A range of alkane! and areneselenolates were shown to undergo a zinc promoted reaction withdichloromethyl methyl ether to give trialkyl and triaryl triseleno!ortho!formate esters in yields of39Ð35) "Equation "63## ð60ZOR362Ł[

RSeH, Zn, Et2O

40–46%RSe

SeR

SeR

OMe

Cl

Cl

(74)

"iii# From ortho!esters

Trans!esteri_cation of ortho!formate esters with methane! or benzeneselenol in the presence ofboron tri~uoride etherate produced the triseleno!ortho!formates "010\ R1�Me# and "010\ R1�Ph#in yields of 70) and 53) respectively "Equation "64## ð73JA2673\ 61CB400Ł[ Trimethyl ortho!acetateand methaneselenol gave trimethyl triseleno!ortho!acetate in 55) yield under these conditionsð68JOM"0660#Ł[ Ortho!esters have also been shown to undergo exchange reactions with boron tri!selenides to give triseleno!ortho!esters "Equation "65##\ though these reactions are subject to stericlimitations[ Thus\ boron tris"benzeneselenide# and triethyl ortho!formate gave triphenyl triseleno!ortho!formate in 65) yield\ boron tris"methaneselenide# and trimethyl ortho!acetate producedtrimethyl triseleno!ortho!acetate in 28) yield\ whereas the reaction between boron tris!"benzeneselenide# and trimethyl ortho!acetate proceeded only very slowly\ a}ording little of thetriseleno!ortho!ester product ð68JOC0772\ 68JOC3168Ł[

R2SeH, BF3•OEt2R2Se

SeR2

SeR2

OR1

R1O

R1O(121)

(75)

B(SeR3)3, cat. TFA, CHCl3R1

SeR3

SeR3

SeR3R1

OR2

OR2

OR2 (76)

5[92[3[0[1 Triseleno!ortho!esters from carboxylic acids02C!Labelled triphenyl triseleno!ortho!formate has been prepared in 37) yield by the acid

catalysed reaction of 02C!labelled formic acid with benzeneselenol "Equation "66## ð73HCA0969Ł[

82Three Seleniums

The preparation of triseleno!ortho!esters from other carboxylic acid derivatives has not beenreported[

PhSeH, HCl, 0 °C, 1 h

then RT, 30 d48%

HC*O2H HC*(SePh)3(77)

5[92[3[0[2 Triseleno!ortho!esters from triselenocarbenium salts

In a manner analogous to the reduction of trithiocarbenium salts discussed in Section 5[92[2[0[3\1!alkaneseleno!0\2!diselenoles may be prepared by sodium borohydride reduction of the cor!responding triselenocarbenium salts[ 1!Methaneseleno!0\2!diselenole "011\ R�Me# was preparedfrom the corresponding triselenocarbenium iodide in a yield of greater than 79) using this method"Equation "67## ð64TL0148Ł\ and the 1!ethaneseleno derivative "011\ R�Et# was similarly preparedfrom the analogous tetra~uoroborate salt ð75ZC027Ł[

NaBH4SeR

Se

Se

Se

Se+ SeR (78)

X–

(122)

5[92[3[0[3 Triseleno!ortho!esters from diselenoacetals and related compounds

A few derivatives of triseleno!ortho!esters have been prepared by the direct electrophilic selenationof diselenoacetals and related compounds[ Reaction of a\a!bis"benzeneseleno#acetaldehyde withmorpholinobenzeneselenamide produced the triseleno!ortho!ester "012^ Equation "68## ð71TL0446\74BSF0108Ł\ and reaction of the selenated enamine "013# with the same reagent gave the additionproduct "014# ð74BSF0108Ł[ Treatment of acetone with red selenium under basic conditions producedthe cyclic selenium salt "015# ð81CC0428Ł[ This reaction proceeds through the diselenoacetal!likeintermediates "016# and "017#\ and involves three electrophilic a!selenation steps "Scheme 14#^ it istherefore a counterpart of the haloform reaction[

CHO

PhSe

PhSe

CHO

PhSe

PhSe

PhSe

OPhSeN

(123)

(79)

PhSe

PhSe

N

O(124)

PhSe

PhSe

N

O(125)

N

O

PhSe

5[92[3[0[4 Triseleno!ortho!formates from tetraseleno!ortho!carbonates

Seebach ð58AG"E#349Ł showed that the lithium triselenomethylide "018# is generated by treatmentof tetraphenyl tetraseleno!ortho!carbonate with n!butyllithium at −67>C "Equation "79##\ and thatthis reacts with deuterated water to give the deuterated triseleno!ortho!formate "029#[ The use oflithiated triseleno!ortho!formates\ for example "018#\ for the preparation of higher triseleno!ortho!esters is discussed in the next section[

83 Three Chalco`ens

Red Se, K2CO3, (Ph3P)2NCl, RT, 16 h

26%

Sex

O

O

Sex

O

Sey

O

SeSe

Se

SeSe

O

SeSe

Se

SeSe

Se– N+(PPh3)2

(127) (128)

(126)

Scheme 25

PhSe

SePh

SePh

SePh Li+SePh

SePh

SePh

(129)

BunLi, THF, –78 °C (80)–

(130)

D

SePh

SePh

SePh

5[92[3[0[5 Higher triseleno!ortho!esters from triseleno!ortho!formate esters

Metallated triseleno!ortho!formates "020# are generated on treatment of triseleno!ortho!formateesters with strong bases^ the lithiated triseleno!ortho!formate "020\ R�Ph# is obtained from tri!phenyl triseleno!ortho!formate and lithium di!s!butylamide at −67>C ð58AG"E#349Ł\ and "020\R�Me# is generated from trimethyl triseleno!ortho!formate and n!butyllithium at −67>Cð68JOM"0660#Ł[ These lithiated triseleno!ortho!formates react with a range of electrophiles to yieldhigher triseleno!ortho!esters[ Thus\ lithiated triseleno!ortho!formates react with] alkyl halides to givealiphatic triseleno!ortho!esters ð58AG"E#349\ 68JOM"066#0\ 71TL2396Ł^ aldehydes to give a!hyd!roxytriseleno!ortho!esters ð58AG"E#349\ 70TL3998Ł\ and epoxides to give b!hydroxytriseleno!ortho!esters ð67TL2860Ł "Scheme 15#[ Tris"tri~uoromethyl# triseleno!ortho!formate yielded the cor!responding triseleno!ortho!acetate "021# on metallation with potassium di!i!propylamide\ followedby treatment with methyl iodide "Equation "70## ð73T3852Ł[ Since metallated triseleno!ortho!formatesmay also be obtained from tetraseleno!ortho!carbonates "Section 5[92[3[0[4#\ these should also beregarded as precursors of higher triseleno!ortho!esters[

R1Se

SeR1

SeR1

Li+SeR1

SeR1

SeR1

(131)

OH

R2 SeR1

SeR1SeR1

OH

R2

SeR1

SeR1

SeR1

R2

SeR1

SeR1

SeR1

O

R2

Li+ –B, THF, –78 °C R2CHO

R2X

Scheme 26

–

84Mixed Includin` Oxy`en

F3CSe

SeCF3

SeCF3

SeCF3

SeCF3

SeCF3

(132)

i, K+ –N(Pri)2

ii, MeI

(81)

5[92[4 MIXED CHALCOGEN FUNCTIONS INCLUDING OXYGEN

Mono! and dithio!ortho!esters are derivatives of carboxylic ortho!esters in which one and two ofthe oxygen substituents respectively are replaced with sulfur substituents[ Similarly\ mono! anddiseleno!ortho!esters are mixed oxygen and selenium functions containing one and two seleniumsubstituents respectively[ Monoselenomonothio!ortho!esters bear one oxygen\ one sulfur and oneselenium substituent[ Oxidised derivatives of several mixed functions containing sulfur are known[Methods for the preparation of mixed oxygen and sulfur functions have been reviewed by Simchenð74HOU"E4#2Ł[

5[92[4[0 Methods for the Preparation of Functions R0C"OR1#"OR2#SR3

5[92[4[0[0 From R0C"X0#"X1#X2

Triphenyl monothio!ortho!formate has been prepared in 31) yield by reaction of chloro!diphenoxymethane with benzenethiol in the presence of pyridine "Equation "71## ð51CB0748Ł[

Cl

OPh

OPh

PhS

OPh

OPh

PhSH, pyridine

42%

(82)

Monothio!ortho!esters have been prepared from the reactions of ortho!ester derivatives withthiols[ Ortho!esters react with one equivalent of n!butanethiol in the presence of aluminum tri!chloride to give monothio!ortho!esters "Equation "72##^ yields are reasonable "54Ð79)# for mono!thio!ortho!formates and !acetates\ but are lower "ca[ 24)# for thio!ortho!benzoates ð57CR"C#0495Ł[This reaction will also proceed in the absence of a catalyst^ monothio!ortho!formates are obtainedin high yields ð58BSF214Ł\ though yields are low for monothio!ortho!acetates and !ortho!benzoates\which are obtained as mixtures with dithio!ortho!esters ð69MI 592!91Ł[ Treatment of the O!acyl ortho!formate ester "35# with a range of thiols in the presence of triethylamine produced the monothio!ortho!esters "022# in yields of 34Ð64) "Equation "73## ð58RTC786Ł[ The acid catalysed trans!esteri!_cation of ortho!esters with 1!hydroxybenzenethiol produced the cyclic monothio!ortho!esters "023#in good yields "69Ð66)# "Equation "74## ð64S559Ł[ Cyclic monothio!ortho!ester derivatives have alsobeen obtained from the exchange reactions of ortho!esters with 1!hydroxyethanethiol ð66MI 592!90Łand 1!thiohydroxyacetic acid ð67IZV357Ł[

R1

OR2

OR2

R1

OR2

OR2

OR2 (83)SBu1 equiv. BunSH, AlCl3, heat

AcO

OEt

OEt

RSH, Et3N, RT, 20 min

45–75%RS

OEt

OEt(46) (133)

(84)

R1

OR2

OR2

,H2SO4, 100 °C, 15 min

70–77%

OH

SH

O

S

R1

OR2

OR2

(134)

(85)

85 Three Chalco`ens

5[92[4[0[1 From monothiocarboxylic esters

Monothio!ortho!benzoate esters have been prepared in yields of 55) or more by reaction of amonothiobenzoate ester with a sodium alkoxide\ followed by alkylation of the thiolate intermediatewith an alkyl iodide "Scheme 16# ð78S573Ł[ However\ this procedure is not suitable for the preparationof monothio!ortho!esters from simple aliphatic monothio esters\ which may undergo deprotonationunder the reaction conditions ð78S573Ł[ Treatment of the hydroxy monothioesters "024\ n�9\ 0#with sodium hydride gave the cyclic thiolate intermediates "025\ n�9\ 0#\ which were methylatedin situ to yield monothio!ortho!esters "026\ n�9\ 0# in overall yields of 24Ð67) "Scheme 17#ð75JA5572Ł[ Unlike the reaction of simple monothio!ortho!esters with alkoxides\ this procedure isapplicable to the preparation of cyclic monothio!ortho!acetate esters as well as monothio!ortho!benzoates[

Ar

S

OR1

Ar

S–

OR1

OR1 Ar

SR2

OR1

OR1NaOR1, R1OH or THF R2I

Scheme 27

NaH, MeCN, 0 °C Me3O+BF4– or MeI

35–78%O

O

O

S

OH

RS–

R O

OMeS

R( )n ( )n ( )n

(135) (136) (137)

Scheme 28

5[92[4[0[2 From dioxo! and oxothiocarbenium salts

Monothio!ortho!esters are obtained from the treatment of dioxocarbenium salts with thiols[ Thisreaction is analogous to the preparation of ortho!esters from dioxocarbenium salts and alcoholsdescribed in Section 5[92[1[0[3[ Reaction of the dimethyl dioxocarbenium salt "027# with meth!anethiol in the presence of triethylamine produced the monothio!ortho!ester "028^ Equation "75##ð76JOC1546Ł\ and the cyclic dioxocarbenium tetra~uoroborate salts "039\ R�Me\ Ph^ n�9\ 0# gavemonothio!ortho!esters "030\ R�Me\ Ph^ n�9\ 0# on treatment with lithium methanethiolate"Equation "76## ð75JA5572Ł[ Alternatively\ the salts "039# could be converted to monothio!ortho!esters "030# by treatment with sodium sul_de\ followed by methylation of the thiolate intermediatewith trimethyloxonium tetra~uoroborate or methyl iodide ð75JA5572Ł[ The stable monothio!ortho!hydrogen ester "032# was obtained by treatment of the bicyclic dioxocarbenium tetra~uoroborate"031# with sodium hydrosul_de "Equation "77## ð79JA6468Ł[

(86)MeSH, Et3N

MeO

OMe

OMeMeO

SMe

OMe

OMe

(138) (139)

+ BF4–

LiSMe

O

OMeS

R( )n

O

O( )nR + BF4

–

(140) (141)

(87)

NaSH

O O O O+

BF4– SH

(142) (143)

(88)

Monothio!ortho!esters may also be prepared from oxothiocarbenium salts by addition of alk!oxides[ Reaction of 1!ethoxythiolenium tetra~uoroborate with sodium ethoxide gave 1\1!diethoxy!


thiolane "Equation "78## ð45CB1959Ł\ and the 1!alkyl! and 1!aryl!1!alkoxy!0\2!benzoxathioles "034#were prepared by treatment of the oxathiolium salts "033# with alcohols in the presence of sodiumhydrogen carbonate "Equation "89## ð68S112Ł[

NaOEt

+

BF4–

S OEt S OEt

OEt(89)

R2OH, NaHCO3, MeCN, 0–5 °C, 10 min

78–97%O

S

O

SR1

OR2

R1

(144) (145)

+

BF4–

(90)

5[92[4[0[3 From monothioacetals and related compounds

The cyclic monothio!ortho!formate "036# has been prepared in 23) yield by methanolysis of theN!p!toluenesulfonylsul_limine "035^ Equation "80## ð74JOC546Ł[ The alkaline reaction conditionshelp prevent the product from undergoing disproportionation reactions[ This procedure is analogousto the preparation of trithio!ortho!esters discussed in Section 5[92[2[0[4[

MeOH, KOH

34%O

S

O

S

OMe

NTos

(146) (147)

(91)

5[92[4[0[4 From 1!alkoxythiophenes

Terrier et al[ demonstrated that the highly electron de_cient 1\3!dinitro!4!methoxythiopheneundergoes addition of methanol on treatment with potassium methoxide to produce the stable salt"037#\ which was isolated as a purple solid in virtually quantitative yield "Equation "81## ð64JOC1800Ł[

KOMe, MeOH, RT, 15 min

ca. 100%S

NO2

OMeO2N S

NO2

O2NOMe

OMe

(148)

K+– (92)

5[92[4[1 Methods for the Preparation of Functions R0C"OR1#"SR2#SR3

5[92[4[1[0 From R0C"X0#"X1#X2

Cyclic dithio!ortho!esters have been obtained from the reactions of a\a!dichloro ethers withdithiolates[ Treatment of dichloromethyl methyl ether with disodium ethane!0\1!dithiolate "gen!erated from ethanedithiol and sodium# gave 1!methoxy!0\2!dithiolane in 57) yield\ and dilithiumpropane!0\2!dithiolate "generated from propane!0\2!dithiol and n!butyllithium# reacted with di!chloromethyl methyl ether to produce 1!methoxy!0\2!dithiane in 34) yield "Scheme 18#ð61HCA64Ł[

HS(CH2)2SH, Na, MeCN

68%

HS(CH2)3SH, BunLi, THF

45%OMe OMeOMe

Cl

ClS

S

S

SScheme 29

87 Three Chalco`ens

Dithio!ortho!esters have also been obtained from exchange reactions of ortho!esters with n!butanethiol ð58BSF214Ł\ though these are normally isolated as side!products from the preparationof monothio!ortho!esters by this method "see Section 5[92[4[0[0# ð69MI 592!91Ł[

5[92[4[1[1 From dithiocarbenium salts

Okuyama et al[ ð76JOC1546Ł prepared the dithio!ortho!ester "049# by addition of sodium methoxideto the dithiocarbenium perchlorate "038^ Equation "82##[ This procedure is analogous to the prep!aration of trithio!ortho!esters by the addition of thiols to dithiocarbenium salts discussed in Section5[92[2[0[3[

(93)NaOMe, MeOH, MeCN

MeO

SMe

SMe

MeO

SMe

OMe

SMe

(149) (150)

+ ClO4–

5[92[4[1[2 From mono! and dithioacetals and related compounds

Dithio!ortho!ester derivatives may be prepared by the reaction of metallated monothioacetals withdisul_des[ Deprotonation of 0\2!oxathiane by treatment with n!butyllithium at −67>C\ followed byreaction with dimethyl disul_de produced 1!methanethio!0\2!oxathiane in 71) yield "Scheme 29#ð70TL1994\ 74JOC546Ł[ In a similar manner\ lithiation of a series of sulfonyl oxiranes "040# followedby treatment with diphenyl disul_de gave the oxidised dithio!ortho!ester derivatives "041# in yieldsof 34Ð89) "Scheme 20# ð80JCS"P0#2980Ł[

i, BunLi, THF, –100 °C

O

S

SMe

O

S ii, MeSSMe

82%O

S– Li+

Scheme 30

i, BunLi, THF, –100 °C ii, PhSSPhO

SPh

SO2PhR1

R2

OSO2PhR1

R2

OSO2PhR1

R2–

Li+

(151) (152)Scheme 31

Lithiation of the unsaturated dithioacetal "042# followed by reaction with benzophenone producedthe bicyclic dithio!ortho!ester "043# in 87) yield "Scheme 21# ð58S06Ł[ This reaction proceeds viacyclisation of the intermediate ketene dithioacetal "044#[ Selenocyclisation of the related hydroxyketenedithioacetal "045# gave the spirobicyclic dithio!ortho!ester "046^ Equation "83## ð79JOC1125Ł[

i, BunLi

ii, Ph2CO S

S

S

S

98%S

S

Li+ OPh

Ph–O

PhPh

(153) (155) (154)Scheme 32


PhSeCl, Et3N, THF, –78 °C

64%S

S

HO S

S

OPh

SePh

Ph

(156) (157)

(94)

Some dithioacetals undergo direct oxygenation on treatment with organic peroxides[ Reaction oftrithiane with t!butyl peroxybenzoate in the presence of copper"I# chloride gave the benz!oyloxytrithiane "53# and dibenzoyloxytrithiane "047^ Equation "84##^ the yield of "53# was at anoptimum "69Ð79) based on recovered trithiane# when 9[6 equivalents of t!butyl peroxybenzoatewere used\ and "047# was obtained as the major product when 2[9 equivalents of t!butyl per!oxybenzoate were used ð63BCJ0385Ł[ 1!Benzoyloxydithiane has been generated by an analogousmethod\ though this product was too unstable to isolate and characterise ð63BCJ0385Ł[

PhCO3But, CuCl, C6H6, heatS

S

S

OCOPhS

S

SS

S

S

OCOPh

PhOCO

+

(64) (158)

(95)

Cyclic dithio!ortho!formates have been prepared by reaction of N!p!toluenesulfonylsul_limines"89# derived from dithioacetals of formaldehyde with alcohols under alkaline conditions "Equation"85## ð65S440Ł[

R3OH, KOH

56–93%SR2

SR1

TosN

R3O

SR1

SR2

(90)

(96)

5[92[4[1[3 Miscellaneous methods

Generation of benzyne in the presence of carbon disul_de and methanol gave 1!methoxy!0\2!benzodithiole in 67) yield "Scheme 22# ð63CC055Ł[ The reaction proceeds via addition of methanolto the carbene "048#\ which is formed by the cycloaddition of carbon disul_de to benzyne[ Amodi_cation of this reaction involves the generation of benzyne by diazotisation of anthranilic acidusing an alkyl nitrite^ in this case\ the alkoxy group of the alkyl nitrite is the source of the 1!substituent of the product benzodithiole "Equation "86## ð64S27Ł[

Pb(OAc)4 CS2 MeOH

S

S

S

S

NN

N

NH2

OMe:

(159)Scheme 33

RONO, CS2

S

SOR

CO2H

NH2

(97)

A series of cyclic oxidised derivatives of dithio!ortho!esters "050# has been prepared by the lithiumt!butyl peroxide oxidation of alkenes "059^ "Equation "87## ð80JCS"P0#2980Ł[

LiO2But, THF, –78 °C to –18 °CO

SR2

SO2Ar

R1

SO2Ar

SR2R1

(160) (161)

(98)

099 Three Chalco`ens

5[92[4[2 Methods for the Preparation of Functions R0C"OR1#"OR2#SeR3

5[92[4[2[0 From 1!alkoxyselenophenes

In an analogous reaction to that described in Section 5[92[4[0[4\ addition of potassium methoxideto 1\3!dinitro!4!methoxyselenophene produced the stable salt "051#\ which was isolated as a purplesolid in virtually quantitative yield "Equation "88## ð64JOC1800Ł[

KOMe, MeOH, RT, 15 min

ca. 100%Se

NO2

OMeO2N Se

NO2

O2NOMe

OMe

(162)

K+– (99)

5[92[4[3 Methods for the Preparation of Functions R0C"OR1#"SeR2#SeR3

5[92[4[3[0 From R0C"X0#"X1#X2

Dihalomethyl methyl ethers react with selenolates to give diseleno!ortho!esters[ Treatment ofdichloromethyl methyl ether with sodium benzeneselenolate "generated by the sodium borohydridereduction of diphenyl diselenide# gave the diseleno!ortho!formate ester "052# in 67) yield "Equation"099## ð68JA5527Ł[ Other dichloromethyl alkyl and aryl ethers gave diseleno!ortho!formates "053\R�alkyl\ aryl# in yields of 31Ð65) on treatment with sodium areneselenolates "generated from theselenophenol and metallic sodium# "Equation "090## ð75ZOR096Ł[ Dichloromethyl ethers also reactwith areneselenomagnesium halides to give diseleno!ortho!formates\ though yields are usually lowerthan those obtained from reaction with the corresponding sodium selenolates ð75ZOR096Ł[ Reactionof dibromomethyl methyl ether with dilithium benzene!0\1!diselenolate gave 1!methoxy!0\2!di!selenole in 27) yield "Scheme 23# ð77HCA0131Ł[

OMe

Cl

Cl

OMe

PhSe

PhSe

NaSePh

78%(100)

(163)

OR

Cl

Cl

OR

PhSe

PhSe

ArSeH/Na, MeO(CH2)2OMe

42–76%

(164)

(101)

Br2CHOMe

38% Se

SeOMe

Li

Li

2 Se, THF/Et2O, –60 °C Se– Li+

Se– Li+

Scheme 34

The cyclic diseleno!ortho!esters "055\ R�H\ Me# have been generated from the boron tri~uorideetherate catalysed exchange reactions between triethyl ortho!formate and the 0\2!diselenolates "054\R�H\ Me^ "Equation "091##[ However\ these products were not isolated and characterised\ butwere used in situ for the preparation of diselenothio!ortho!esters "see Section 5[92[5[1[0# ð78H"17#278Ł[

HC(OEt)3, BF3•OEt2

Se– Li+

Se– Li+

R Se

Se

ROEt

(165) (166)

(102)

5[92[4[4 Methods for the Preparation of Functions R0C"OR1#"SR2#SeR3

5[92[4[4[0 From monothioacetals and related compounds

Monoselenomonothio!ortho!ester derivatives have been prepared from the reactions of lithiatedmonothioacetals with diselenides[ Lithiation of 0\2!oxathiane with n!butyllithium followed by reac!

090Mixed Sulfur And Selenium

tion with dimethyl diselenide produced 1!methaneseleno!0\2!oxathiane in 49) yield "Scheme 24#ð70TL1994\ 74JOC546Ł[ In a similar manner\ lithiation of the sulfonyl oxiranes "040# followed bytreatment with diphenyl diselenide gave the oxidised selenothio!ortho!ester derivatives "056# in yieldsof 14Ð81) "Scheme 25# ð80JCS"P0#2980Ł[


O

S

SeMe

O

S ii, MeSeSeMe

50%O

S– Li+

Scheme 35

i, BunLi, THF, –100 °C ii, PhSeSePh

25–92%

O

SePh

SO2PhR1

R2

OSO2PhR1

R2

OSO2PhR1

R2–

Li+

(151) (167)

Scheme 36

5[92[5 MIXED SULFUR AND SELENIUM FUNCTIONS

Monoselenodithio! and diselenomonothio!ortho!esters are mixed sulfur and selenium functionswhich bear one and two selenium substituents respectively[

5[92[5[0 Methods for the Preparation of Functions R0C"SR1#"SR2#SeR3

5[92[5[0[0 From R0C"X0#"X1#X2

1!Chloro!0\2!dithianes react with areneselenolates to give 1!areneseleno!0\2!dithianes[ Thus\ di!thianes "058\ R0�H^ R1�H\ Me\ OMe\ F\ Cl\ NMe1\ CF2# were prepared from 1!chloro!0\2!dithiane and the appropriate sodium areneselenolates "prepared by reduction of the correspondingdiaryl diselenide using either sodium borohydride or metallic sodium and ultrasound# ð77JOC2655Ł[Similar reaction of the 1!chloro!3\5!dimethyl!0\2!dithiane "057\ R0�Me# with sodium "p!methoxy!benzene#selenolate gave the selenodithio!ortho!ester "058\ R0�Me^ R1�OMe#\ which was obtainedas a ca[ 4 ] 0 mixture of diastereoisomers "Equation "092## ð77JOC4557Ł[

S

S

Cl

R1

R1

S

S

Se

R1

R1

R2

Na+ –Se R2, C6H6

(168) (169)

(103)

5[92[5[0[1 From selenodithiocarbenium salts

1!Methanethio!0\2!selenothiolium salts are reduced to 1!methanethio!0\2!selenothioles by sodiumborohydride[ Reduction of the ~uorosulfonate salt "069# gave the 1!methanethio!0\2!selenothiole"060# in 69) yield "Equation "093## ð79H"03#160Ł\ and similar treatment of the iodide salts "061\R�H\ Me# produced the analogous selenothioles "062\ R�H\ Me# ð64TL0148Ł[

091 Three Chalco`ens

NaBH4, EtOH

70%

SMeSe

SPh

SMe FSO3–

Se

SPh

+

(170) (171)

(104)

SMe I–Se

SR

+

(172)

SMeSe

SR(173)

5[92[5[0[2 From dithioacetals

Selenodithio!ortho!esters may be prepared by the selenation of lithiated dithioacetals[ Deprot!onation of 0\2!dithiane using n!butyllithium followed by reaction with p!nitrobenzeneselenyl cyanideproduced the 1!seleno!0\2!dithiane "063# in 12) yield "Scheme 26# ð77JOC2655Ł[ However\ treatmentof lithiated 0\2!dithiane with the diaryl diselenides "064\ R�OMe\ CF2# gave only very low yieldsof the selenated compounds "065\ R�OMe\ CF2# ð75CJC621Ł[

S

S O2N SeCN

23%

BunLi, THF, –20 °C

S

S– Li+

S

S

Se NO2

(174)Scheme 37

Se R

(175)

SeRS

S

Se R

(176)

5[92[5[1 Methods for the Preparation of Functions R0C"SR1#"SeR2#SeR3

5[92[5[1[0 From diseleno!ortho!esters

Pinto et al[ ð78H"17#278Ł reported the preparation of the diselenothio!ortho!esters "066\ R�H\Me# from the corresponding O!ethyl diseleno!ortho!esters by treatment with benzenethiol[ Thestarting diseleno!ortho!esters were generated by the boron tri~uoride etherate catalysed reactionbetween dilithium diselenides and triethyl ortho!formate "see Section 5[92[4[3[0#\ and were used insitu[

PhSH

Se

Se

ROEt

Se

Se

RSPh

(177)

(105)


6.04Functions Containing aChalcogen and Any OtherHeteroatoms Other Than aHalogenMARTIN J. RICEZENECA Agrochemicals, Bracknell, UK

5[93[0 FUNCTIONS CONTAINING CHALCOGEN AND A GROUP 04 ELEMENT 093

5[93[0[0 Functions Bearin` Chalcoèn and Nitroèn 0935[93[0[0[0 Functions bearin` oxyèn and nitroèn 0935[93[0[0[1 Functions bearin` sulfur and nitroèn 0005[93[0[0[2 Functions bearin` selenium and nitroèn 004

5[93[0[1 Functions Bearin` Chalcoèn and P\ As\ Sb or Bi 0055[93[0[1[0 Functions bearin` oxyèn and P\ As\ Sb or Bi 0055[93[0[1[1 Functions bearin` sulfur and P\ As\ Sb or Bi 0085[93[0[1[2 Functions bearin` selenium and P\ As\ Sb or Bi 012

5[93[1 FUNCTIONS CONTAINING CHALCOGEN AND A METALLOID AND POSSIBLY AGROUP 04 ELEMENT 013

5[93[1[0 Functions Bearin` Chalcoèn and Boron 0135[93[1[1 Functions Bearin` Chalcoèn and Silicon 013

5[93[1[1[0 Functions bearin` oxyèn and silicon 0135[93[1[1[1 Functions bearin` sulfur and silicon 0155[93[1[1[2 Functions bearin` selenium and silicon 029

5[93[1[2 Functions Bearin` Chalcoèn and Germanium 0295[93[1[2[0 Functions bearin` oxyèn and èrmanium 0295[93[1[2[1 Functions bearin` sulfur and èrmanium 021

5[93[2 FUNCTIONS CONTAINING CHALCOGEN AND A METAL AND POSSIBLY A GROUP 04ELEMENT OR A METALLOID 022

5[93[2[0 Functions Bearin` Oxyèn and a Metal 0225[93[2[0[0 Functions bearin` two oxyèns and a metal 0225[93[2[0[1 Functions bearin` oxyèn\ silicon and a metal 0225[93[2[0[2 Functions bearin` oxyèn and two metals 022

5[93[2[1 Functions Bearin` Sulfur and a Metal 0225[93[2[1[0 Functions bearin` sulfur\ oxyèn and a metal 0225[93[2[1[1 Functions bearin` two sulfurs and a metal 0235[93[2[1[2 Functions bearin` sulfur\ boron and a metal 0245[93[2[1[3 Functions bearin` sulfur\ silicon and a metal 0245[93[2[1[4 Functions bearin` sulfur and two metals 024

5[93[2[2 Functions Bearin` Selenium and a Metal 0245[93[2[2[0 Functions bearin` selenium\ sulfur and a metal 0245[93[2[2[1 Functions bearin` two seleniums and a metal 024

092

093 Chalcoèn and Any Other Heteroatoms

5[93[2[2[2 Functions bearin` selenium\ phosphorus and a metal 0255[93[2[2[3 Functions bearin` selenium\ silicon and a metal 025

5[93[0 FUNCTIONS CONTAINING CHALCOGEN AND A GROUP 04 ELEMENT

The compounds in this class have been the subject of several reviews ð58ZC190\ B!69MI 593!90\ 60S05\66UK574\ B!68MI 593!90\ 68T0564\ 74HOU"E4#2Ł[

5[93[0[0 Functions Bearing Chalcogen and Nitrogen

Functional groups bearing chalcogen and nitrogen are available by modi_cation of precursorswhich contain sp2! or sp1!carbon atoms\ via cycloadditions or by other miscellaneous methods[ Thisgeneral order is adhered to throughout this section[

5[93[0[0[0 Functions bearing oxygen and nitrogen

"i# Functions bearin` two oxyèn and one nitroèn substituent

The functional group containing two ether type oxygens and one amine type nitrogen singlybonded to a carbon is most commonly referred to as an amide acetal[ In the majority of cases\ allthe heteroatoms are substituted further[ Exceptions are the cyclols which have one unsubstitutedoxygen atom[

"a# From sp2!carbon compounds[ Amide acetals can be accessed by transacetalation of otheramide acetals ð50LA"530#0\ 52AG185\ 53CCC534\ 54HCA0635\ 57CB30Ł with alcohols[ Typically\ the startingmaterial is N\N!dimethylformamide dimethyl acetal "0#[ The uncatalysed reaction is driven tocompletion by the removal of generated methanol by distillation[ The use of sterically hinderedalcohols can\ however\ lower the reaction yields signi_cantly[ Cyclic amide acetals "1# are availablefrom diols "Scheme 0# ð50LA"530#0\ 53CCC534\ 57CB30Ł[ Transamidation can be achieved with highboiling amines such as morpholine and piperidine ð50LA"530#0\ 55USP2128408Ł[ Simultaneous trans!acetalation and transamidation has also been reported ð53CCC534Ł[

Scheme 1

Me2N

OMe

OMe O

OMe2N

Me2N

OR

OR

HOOH

ROH

(1)

(2)

Cyclols "3# are relatively rare in the literature\ existing as equilibrium mixtures with the cor!responding ring!opened hydroxyamides "2#\ and more commonly they have been proposed astransient reaction intermediates "Equation "0## ð59CRV43\ 52CCC1939\ 52TL328\ 53JOC1658\ 53TL36\55UKZ193\ 57TL1602Ł[ O!Alkylation ð51TL690\ 52T0550\ 52T0564\ 54T2426Ł generates fully substitutedamide acetals[

O

NH RHO NH

OHO

R

(3) (4)

(1)

Symmetrical amide acetals "4# are obtained from ortho!esters with a variety of nitrogen nucleo!philes such as sulfonamides "Equation "1## ð50JOC3204\ 54AJC0856\ 79JOC3927\ 71JCS"P0#1760\ 77JHC896Ł\ureas ð42JA560\ 52HCA1295Ł\ imidazoles ð79JOC3927Ł and di~uoroamine ð56JA605Ł[

094Chalco`en and Group 04

R1

OR2

OR2

OR2 R1

OR2

OR2

NR3R4R3R4NH

(5)

(2)

Under Lewis acid catalysis\ isocyanates will react to give N!carboxy compounds "5# "Equation"2## ð51AG"E#481\ 55GEP0045679Ł[ Cyanide can be displaced from "a!alkoxy!a!alkylamino#acetonitriles"6# ð61CB0239Ł or\ in addition to one of the alkylamino groups\ from a\a!bis"dialkylamino#acetonitriles "7# by alkoxides ð38LA"451#118\ 61CB0239Ł[ Both halogens in a\a!di~uorotrialkylamines"8# have been replaced by alcohols ð52USP2981526\ 53USP2010973\ 54USP2103301\ 72TL0924Ł[ Chloro!diaryloxymethanes have been used to generate diaryloxymethyltriethylammonium chlorides "09#with triethylamine ð47JPR"6#69Ł[ Such reactive compounds give amide acetals on further reactionwith amines ð61S21\ 61S307\ 62S312\ 64S161Ł[

R1O

OR1

OR1

R1O

OR1

NR2CO2R1

R2NCO, BF3

(6)

(3)

NC

NR12

OR2

(7)

NC

NMe2

NMe2

(8)

R1

F

F(9)

NR22 Et3N+

OAr

OAr(10)

Cl–

"b# From sp1!carbon compounds[ The halogen in N\N!dialkyliminium chlorides "00# can be dis!placed on treatment with alkoxides to yield amide acetals "01# "Equation "3## ðB!69MI 593!90\ 61TL3106\B!68MI 593!90Ł[ In a similar manner\ alkoxide can be displaced from alkoxyiminium salts "02#ð50LA"530#0\ 57PAC408\ B!69MI 593!90\ B!68MI 593!90Ł and thiolate from alkylthioiminium salts "03#ð56BCJ1530Ł[ Lactam acetals are also accessible by this methodology ð52USP2981526\ B!68MI 593!90Ł[In addition\ pyridine has been demonstrated to react with the oxonium salt "04# to give thepyridinium species "05# ð60S201Ł[ The adduct "06# is formed by capture of the N!acyloxazolium saltwith methoxide ð64JCS"P0#0291Ł[

(4)R12N

OR2

OR2

NaOR2

(12)

Cl

H NR12

+

(11)

OR2

H NR12

+

(13)

SEt

H NMe2+

(14)

+

(15)

EtO OEtBF4

–

(16)

N

OEt

OEt

+

(17)

N

O

O

NO

MeO

O

Formamide acetals are produced by the reaction of N\N\N?\N?!tetrasubstituted formamidium saltswith sodium alkoxides ð59AG845\ 51JOC2553\ 52GEP0035781\ 53CCC534Ł[ Tetrakis"dimethylamino#ethene"07# is converted by methanol into a mixture of amide acetals "08# and "19# ð61T0854Ł[ Hexa!~uoropropene "10# combines with diethanolamine "11# to generate an azadioxabicycloð2[2[9Łoctane


"12# ð61TL2846Ł[ Similar systems\ such as "14#\ are obtained by the reaction of the sodium salts ofdialkanolamines such as "13# with nitriles "Scheme 1# ð62AG"E#885Ł[

NMe2

NMe2Me2N

Me2N OMe

OMe

Me2N

OMe

OMe

MeO

Me2N

NMe2

HO

HN

OH CF3

F

N

OO

F3C F

i, Naii, EtCN

Et3N

(18) (19) (20)

(22) (21)

HO

HN

OHN

OO

+MeOH

+

(23)

(24) (25)

F

F

Scheme 2

"c# Cycloaddition methods[ The unsubstituted ketene acetal "15# reacts with isocyanates to givebarbituric acid acetals "16# ð48MI 593!90\ 51AG"E#220\ 55CB2781Ł while the cyclic analogue "17# generatesthe b!lactam "18# ð77TL1216Ł[ Similarly\ tetramethoxyethene gives the azetidin!1!one "29# "Scheme2# ð48MI 593!90\ 53AG"E#279Ł[ Ketene acetals will also react with nitrosobenzene\ with dialkyl azo!dicarboxylates ð60CB762Ł and with ketenimines ð65IZV747Ł to give four!membered ring products"20#\ "21# and "22#[

OEt

OEt

EtO

EtO

NHPh

O

N

N

O

Ph

O

PhOEt

OEt

O

O

O

O

NO

Ph

MeO

MeO

OMePhNCO

OMeN

MeOMeO

MeOMeO

O

Ph

PhNCO

(27)(26)

PhNCO

PhNCO

(29)(28)

(30)

Scheme 3

N

O

MeOMeO

MeOMeO Ph

(31)

N

N

MeOMeO

MeOMeO CO2Me

(32)

CO2Me

N

(33)

Ph

OEtOEt

CF3

F3C

Dichloroketene acetals such as "23# react with sulfamyl chlorides to give four!membered ringproducts "24# "Equation "4## ð56JA1491\ 61JA5024Ł[ a\b!Unsaturated ketones combine with ynaminesð69CR"C#357Ł and with 0!dialkylamino!0!alkylthioethenes ð56BCJ1530Ł to give bicyclic amide acetals"Scheme 3# ð57TL386Ł[


O O

Cl ClSO2

N

ClCl

EtEtNHSO2Cl

O

O

(34) (35)

(5)

R2N

MeS

O2

O ONR2

O2

R2N

Scheme 4

An unsymmetrical bicyclic amide acetal "26# has been obtained by treatment of the dihydrooxazole"25# with benzonitrile oxide ð60AG"E#709Ł[ Dialkoxydihydro!0\1\2!triazoles such as "27# are producedby the reaction of azides with some ketene acetals ð52G831\ 57G570\ 61JHC0976\ 65JHC194Ł[ Cyclo!propanone acetals such as "28# undergo ring expansion with aryl isocyanates to give g!lactam acetals"39# "Scheme 4# ð76JCR"S#251Ł[

(40)

O

NN+ O–Ph N

O ON

Ph

PhNCO

(36)

PhN N+ N–

MeO

MeO

N

NN

MeO

MeO

Ph

+

(37)

N

O

Ph

OMeOMe

OMeMeO

HEtO2C

H

EtO2C

H

+

(38)

(39)

Scheme 5

"d# Miscellaneous reactions yieldin` amide acetals[ The imidate "30# has been oxidized by mcpbato the corresponding oxaziridine ð60TL3408\ 62TL0796Ł[ t!Butyl hypochlorite has been used to oxidisea 3!oxa!b!lactam "31# to the amide acetal ð71H"07#190Ł[ Benzoylhydrazones "32# react with leadtetraacetate to give 1\4!dihydro!0\2\3!oxadiazoles ð56TL2490\ 57CB2740Ł[ Reductive conditions areexempli_ed by the reaction of N\N!dimethylformamide and N\N!dimethylacetamide with 0\2!dibro!moketones and a zinc:copper couple to give amide acetals "33# "Scheme 5# ð61JA2190Ł[

The insertion of ethoxycarbonylnitrene\ generated by photolysis of ethyl azidoformate\ intoacetals ð56T34Ł and ketene acetals ð61JHC0976Ł leads to N!carboxy amide acetals such as "34#[Dichlorocarbene reacts with dialkylamines and sodium alkoxides to give the amide acetalsHC"OR0#NR1

1 resulting from insertion and double halogen displacement ð53GEP0050174\ 58LA"614#04\58RTC178Ł while the diazo compound "35# on photolysis undergoes cyclisation to the dihydrooxazole"36# ð63JHC418Ł[ Epoxides add to dihydrooxazoles "37# and 4\5!dihydro!3H!0\2!oxazines to givebicyclic amide acetals such as "38# ð55AG"E#764\ 55AG"E#783\ 55LA"587#063Ł[ The bicyclic amide acetal"49# was obtained by the addition of diketene to the C1N bond of a chiral oxazoline "Scheme 6#ð80TL486Ł[

N!Methylpyrrole undergoes anodic oxidation in methanol to generate the symmetrical product"40# ð55JOC3943Ł[ Under basic conditions\ the diazene oxide "41# reacts with methanol to give theazo compound "42# ð67JOC0348Ł[ Ozonides "43# are formed by the reaction of ozone with indoles


LiOMe, ButOClN

OOMe

O

HN

O-TMS

PhO

O O

Ph Ph

N

O

O

HN

O-TMS

PhO

O O

Ph Ph

NN

O

N

Et

Et

NH O

Ph Et

Et OAc

PhPb(OAc)4

(42)

(43)

Scheme 6

Zn–Cu OO

R3

R4

O

R1

BrR2

R3

BrR4

NMe2R5

mcpba, CH2Cl2

R2R1

(41)

(44)

+ R5CONMe2

MeO NBut

ONMeO

But

OO

O

ONH

CO2Et

N

OPh OEtN2

Ph

HN

CO2EtMeO OMe

MeOOMe

LiClN

OOO

N O Ph

EtPh

Et

(45)

(47)

+ N3CO2Ethν

(50)

hν

N

O O

O

H

But

(49)(48)

+

Scheme 7

(46)

ð41JA2744Ł[ Compounds of this type have also been obtained by cyclisation of hydroperoxidesð41CB838Ł[ The reaction of some cyclic ortho!esters with TMS azide leads to the formation ofdisplacement products such as "44# "Scheme 7# ð68TL402Ł[

"ii# Functions bearin` one oxy`en and two nitro`en substituents

Functions bearing two nitrogens and one oxygen are known commonly as ester aminals[ Aswith the amide acetals\ they are synthetically accessible from sp2! and sp1!carbon compounds\ bycyclisations\ by cycloadditions and by other miscellaneous methods[


N

Me

N

Me

OMe

OMeMeO

MeO

Et3N, MeOHN N

Ph

OPrn

MeO

N N

Ph

OPrn

(51)

–O

hν

+

(52) (53)

Scheme 8

NH

O

R

Ar

O

O

(54) (55)

O O

N3

"a# From sp2!carbon compounds[ Some examples of the formation of ester aminals by dis!placement reactions are shown in Scheme 8[ Treatment of bis"dimethylamino#acetonitrile withsodium ethoxide yields the ester aminal "45# ð61CB0239Ł[ The base induced cyclisation of 0!chloro!4\4\4!trinitropentan!1!ol "46# occurs with the elimination of nitrite ð54AG316Ł[ All three halogensare displaced in the reaction of chloroform with aziridine and sodium methoxide ð58LA"614#04Ł[Reaction of triethyl ortho!acetate with the 1!aminobenzenecarboxamide "47# leads to the 1!ethoxyquinazolinone "48# ð89JHC0842Ł[

NC

NMe2

NMe2

EtO

NMe2

NMe2

OH

C(NO2)3

O NO2

NO2

ClCl

(57)

HN

OMe

N NNaOMe

NaOH

CHCl3 +

NaOEt

(56)

Scheme 9

AcOH

NH2

NH

OOEt

OEtNH

N

O

OEt

+

(58) (59)

OEt

"b# From sp1!carbon compounds[ Electron!de_cient heterocycles undergo a range of relatedadditions of water and alcohols ð73CHEC"2#80Ł[ Some examples of these reactions are shown inScheme 09[ {Covalent hydration| is exempli_ed by the addition of the elements of water to thetetrazoloquinazoline "59# ð54JOC718\ 56KGS0985Ł[ An intramolecular addition occurs when the dini!tropyridine "50# is treated with base ð57TL548Ł[ Diethylamine reacts with 4!phenyl!0\1\3!dioxazolin!2!one "51# ð61JPR034Ł[ An analogous reaction occurs when 0\2\3!oxadiazolium salts are treated


with secondary amines leading to tertiary products^ primary amines lead to ring!opened productsð60JCS"C#398Ł[

N N NN

N

HN N NN

N

OH

N

O2N NO2

OOH

NH

O2N NO2

O

ONaOMe

Et2NH

NH

OO

ON

OO

O

PhPh

Et2N

2M HCl

(60)

(61)

(62)

Scheme 10

In a reaction analogous to that with the oxazoline "37#\ epoxides have been demonstrated to reactwith dihydroimidazoles and tetrahydropyrimidines to give ester aminals ð69LA"631#017Ł[

"c# Cycloaddition methods[ Reaction of p!nitrophenyl isocyanate with O!alkyllactims such as"52# leads to 3!alkoxy!0\2!diazetin!1!ones "Equation "5## ð62TL0108Ł[

N

N

N

NO2

O

OMe

OMeNCO

O2N

+

(63)

(6)

"d# Miscellaneous reactions yieldin` ester aminals[ Addition of a!tetralone to the bisurea "53#in ethanolic hydrogen chloride a}ords a 1!hydroxyhexahydroquinazoline "54# ð55IZV87Ł[ A 2!"dimethylamino#oxaziridine "55# is formed by photocyclisation of the nitrone "56# ð60JA3964Ł[ Thereaction of hydrazoic acid with ethoxypropyne gives bisazide "57# "Scheme 00# ð46RTC838Ł[

O NHH N

OH

ArH2NCONH

H2NCONH Ar

N

O

N+

Ph NMe2

Me O–Me

Me2N

Ph

+

(65)

OEt

(64)

Et

N3

N3

OEt

hν

+ HN3

(67) (66)

(68)

Scheme 11


5[93[0[0[1 Functions bearing sulfur and nitrogen

"i# Functions bearin` one sulfur\ one nitroèn and one oxyèn substituent

Functional groups bearing oxygen\ sulfur and nitrogen are nonsymmetrical\ and this reduces thenumber of synthetic routes available for their preparation compared to their symmetrical analogues[

"a# From sp2!carbon compounds[ Two examples of formation of this functional group by dis!placement are shown in Scheme 01[ Triethyl ortho!formate reacts with 1!thiolbenzamide to give adihydrobenzothiazine "58# ð58T4884Ł[ Displacement of aniline from the 0\2\3!thiadiazoline "69# byethanol produces the 4!ethoxy analogue "60# ð65ACS"B#726Ł[

Scheme 12

S

NH

O

EtO

OEt

OEt OEtSH

CONH2

EtOH

S

NNPh Ph

NHPhPh S

NNPh Ph

OEtPh

+2-Naphthyl-SO3H

(69)

(70) (71)

"b# From sp1!carbon compounds[ The N!alkylbenzothiazolium cation "61# reacts with the 1!hydroxybenzaldehyde "62# to give the spiro compound "63# ð61HCA0671Ł^ there are other examples ofintramolecular cyclisation of benzothiazolium cations with phenolic ð58T4884Ł and ketonic functionsð89IJC"B#079Ł in the presence of base\ and related reactions of thiazoles ð73H"11#170Ł[ The dime!thylformamide monothioacetal "64# is prepared by O!methylation of N\N!dimethylformamide withdimethyl sulfate\ and subsequent interception of the iminium cation "65# with sodium ethanethiolateð60BSF2243Ł[ An alternative approach\ the interception of a thioimidate with an alcohol\ has alsobeen reported ð73H"11#02Ł[ Reaction of 1!"1?!thiolphenyl#dihydroimidazole "66# with phthalolylchloride gave the spiro thioacetal "67#[ In this reaction it may be the cyclic tautomer "68# of phthaloylchloride which is the reactive species "Scheme 02# ð77LA488Ł[

"c# Cycloaddition methods[ Benzonitrile oxide can undergo 0\2!dipolar cycloadditions to C1Sor to C1N bonds which lead to amide thioacetals[ Two examples of such reactions\ leading to theoxathiazole "79# ð68CB0762Ł and to the fused azetidine "70# ð89TL012\ 80JHC370Ł are shown in Scheme03[ The reaction of keteneÐsulfur dioxide adduct with the 1!aryldihydrooxazoles "71# gives thecycloadduct "72# ð58JHC618Ł[ The dihydroindole "74# was obtained from the reaction of dichloro!ketene with the indole "73# "Scheme 04# ð78JOC0671Ł[

"d# Miscellaneous reactions yieldin` amide monothioacetals[ 3!Thio!b!lactam "75^ R�H# under!goes oxidation with lead tetraacetate ð63JCS"P0#11Ł or with t!butyl perbenzoate in benzene ð68CC374Łto give O!acylated derivatives "75^ R�OCOMe or OCOPh#[ Phenacyl bromide reacts with phenyl!propiolic thioanilide "76# in the presence of acetone to produce a 0\2!oxathiole "77# "Scheme 05#ð64LA847Ł[

"ii# Functions bearin` two sulfur and one nitroèn substituent

There are many parallels that can be drawn between the preparation of thioamide acetals andtheir oxa analogues[ It is likely that many of the principles behind the methods for preparation ofthe latter could be applied to the former[

"a# From sp2!carbon compounds[ Reaction of amide acetals with thiols provides a route to bothacyclic and cyclic thioamide acetals "78# and "89# "Scheme 06# ð58BSF221\ 69BSF1902Ł[ Replacementof the alkoxy function of the dithio!ortho!ester "80# has been demonstrated to give the amidedithioacetal "81# ð79PJC034Ł[ a!Chlorothioacetals such as "82# are converted into amide thioacetals"e[g[ "83## by treatment with amines ð50LA"530#10Ł[

"b# From sp1!carbon compounds[ The reaction of alkoxyiminium cations such as "65# with thiolatesalts in excess leads to amide thioacetals HC"SR0#1NR1

1 ð54IZV1068\ 62CB2614Ł[ Chloroiminium saltsreact with thiols in a similar way ð59MI 593!90Ł and "alkylthio#iminium cations "84# have also been


Cl

Cl

O

O

piperidine

(75)

Na2CO3

PhCH2NEt3Cl–

N+

S

OMe

Me

CHO

HO

MeO NO2N

S

Me

O NO2

MeO

MeO

+

(72) (73) (74)

Me2N

OMe

SEtN+

Me

OMe

Me(76)

S

N

N

O

O

SH

ONH

N O

ClCl

EtS–

+

(77) (79) (78)

Scheme 13

+

N

CN

ON

SS

Ph

O

PhCN

N O

PhN+ O–Ph

N

SEt

NN

OSEt

Ph

N+ O–Ph

Scheme 14(81)

(80)

O2NO

NO2N N

O2S

O

O i, SO2ii, ketene

(82) (83)

Scheme 15

Zn–Cu

N

SO2Ph

N

SO2Ph

S+

O–

Me

O

O

SMe

ClCl

+ Cl3CCOCl

(84) (85)


Scheme 16

N

BrBr SMe

R

CO2Me

O

PhBr Ph

S

NHPhO S

Ph

NHPh

Ph

O+

(86) (87) (88)

Scheme 17

Me2N

OMe

OMe

HSC7H15

(89)

Me2N

SC7H15

SC7H15

HSSH S S

NMe2

(90)

(91)

S S

Ph Ph

OMe

(92)

S S

Ph Ph

NO O

(93)

Cl

SMe

SMe

(94)

Me2N

SMe

SMe

intercepted with thiols to give thioamide acetals ð54BCJ1096\ 55BCJ1994\ 72CI"L#194Ł[ 0\2!Thiazoliumcations "85# undergo reaction with azide anions and with amines to give the addition products "86^X�N2 or NR1# ð54JCS21\ 65BCJ2456\ 65JPR016\ 79JOC1913\ 70JCS"P0#507Ł[ Reduction of the C1Nbond of the iminium salt "87# with sodium borohydride yields the corresponding amide thioacetalð58CPB0813Ł[ A more unusual example is that provided by the reaction of the tris"alkylthio#boranederivatives "88# with amides "Equation "6## ð55IZV253\ 68ZN"B#888Ł[

(95)

+NR32

R1 SR2

(96)S

S+

(97)S

SX

S S

Ph

N+

(98)

X–

O

R1 NR22

R3S B

SR3

SR3

R1

SR3

SR3

NR22+

(99)

(7)

"c# Cycloaddition methods[ The ð1¦1Ł cycloaddition of ketenes to iminodithiocarbonate estershas been used as a route to b!lactams which incorporate the amide dithioacetal function[ Exampleswith cyclic ð46CB1359\ 62JHC680Ł and acyclic ð65JOC0001\ 76S889Ł iminodithiocarbonates are shownin Scheme 07[ Dihydrothiazoles also react with the keteneÐsulfur dioxide adduct "in a manner


analogous to that shown for the oxazoline "71## to give products which contain this functionalityð58JHC618Ł[

N

N3

O

CO2But

MeSMeS

N

MeS SMe

CO2But

+ ClCOCH2OMeEt3N

+ ClCOCH2ON3

Et3N

N

S

N

SMeS

O

MeO SMe

Scheme 18

"d# Miscellaneous reactions yieldin` amide thioacetals[ Photo!rearrangement of N!"ethoxy!acetyl#tetrahydro!0\2!thiazine!1!thione gives the thiazolidinone "099# "Equation "7## ð75TL0224Ł[There are several routes to compounds containing methanesulfonyl functions[ The azo compound"090^ R�H# has been obtained by the reaction of bis"methanesulfonyl#methane with benzene!diazonium chloride ð40RTC622Ł and from its analogue "090^ R�SMe# by reaction with piperidineð40RTC781Ł[ Reaction of diazomethane with the oxime "091# gave the N!methoxyaziridine "092#ð49RTC0112Ł[

N S

N

SS

SO

EtO

O

EtOhν

(100)

(8)

N NPh

R

SO2Me

(101)

SO2Me

(102)

N

MeO2S SO2Me

OMe

(103)

N

MeO2SSO2Me

OMe

"iii# Functions bearin` one sulfur and two nitro`en substituents

"a# From sp1!carbon compounds[ Addition to alkylthioiminium salts "093# by sodium azide andsubsequent cyclisation gives thiatriazoles "094# ð63JCS"P0#439Ł[ Amines will add in a similar mannerto the C1N bond of thiazolium cations such as "095# ð60CPB1111\ 76JOC1904Ł and to 2!methylthio!0\1\3!dithiazolium cations "096# ð63JCS"P0#439Ł[ Phenylmagnesium bromide adds to both the C1Cand the C1N bonds of 4!arylidine!1!phenyliminothiazolidin!3!ones "097# ð53T14Ł[ Treatment ofhydrazonyl halides with thioamides leads to 1\1!disubstituted dihydro!0\2\3!thiadiazoles "098#ð65ACS"B#726Ł[

+

O

N Ph

SMe

(104) (105)

O

N Ph

S

NN

NMe

(106)

N S

Ar

+

"b# Cycloaddition methods[ Cycloaddition of cyclopentadiene to thiocarbonylbis"0\1\3!triazole#"009# gives the adduct "000# ð79JOC2602Ł[ Diphenylethyne reacts under photochemical conditions tothe C1S bond of "001# to give both four! "002# and six! "003# membered ring adducts "Scheme 08#ð65TL2452\ 79LA762Ł depending on the wavelength employed[ Acid chloride derived ketenes undergo


(107)

+SS

NPh SMe

(108)

HN

S NPh

O

Ph

(109)

HNN

S

Ph

NHPh

Ph

Ph

ð1¦1Ł cycloaddition with tetrahydro!1!alkylthiopyrimidines to yield thio substituted b!lactams suchas "004# ð73TL0738Ł[ Trichloroacetyl isocyanate reacts with mesoionic thiazoles to give cycloadductssuch as "005# ð65ACS"B#726\ 65JOC702Ł[ Amide thioacetals react with aryl isocyanates to furnishthe imidazolinediones "006# ð62CB2614\ B!68MI 593!91Ł^ a similar reaction occurs with N!alkyl!0\2\3!thiadiazolium salts ð77LA594Ł[

"c# Photoreduction[ The C1S bond of 0\2!diphenyl!1!thioparabonate "007# undergoes photo!reduction in ethanol ð58BCJ1212Ł[

S

N N

N

N N

NN

N

NN

N N

S

NNNN

SN

NSMe

S

Me

OO

Ph Ph

Ph

Ph

MeMe

O O

Me

MeO

O

+

(110)

Ph

(111)

+ orhν

(112) (113) (114)

Scheme 19

(115)

N N

OCBZ

MeS

PhO

(116)

N N

O O

COCCl3Ph

Ar

S

N

N

Ar

O

ArO(117)

RS

Me2N NNPh

S

Ph

OO

(118)

5[93[0[0[2 Functions bearing selenium and nitrogen

"i# Functions bearin` one selenium\ one oxy`en and one nitro`en substituent

The 1!methoxydihydroselenazole "008^ Ar�3!PhC5H3# has been obtained from the correspondingN!methylselenazolium cation by reaction with sodium methoxide ð70ZOB0731Ł[ Similarly\ treatmentof a N!alkylbenzoselenazolium cation "019# with a 1!hydroxybenzaldehyde derivative generates a1!spiro derivative "010# ð60BSF445\ 80CL0762\ 82CL02Ł[

N

SePh

Me

(119)OMe

Ar

Se

N

R1

(120)

+

(121)

Se

N

O NO2

R2O

R1


"ii# Functions bearin` one selenium\ one sulfur and one nitroèn substituent

Selenium substituted b!lactams such as "011# have been obtained by cycloaddition of ketenes to1!alkylselenothiazolines ð75JAP50047875\ 75JOC3626\ 76NKK0336Ł[

(122)

N

S

CO2Me

MeO

O

SeMe

"iii# Functions bearin` one selenium and two nitroèn substituents

Two examples of such compounds are provided by the selenide "012# which was obtained from0\0!dinitroethane and benzeneselenyl chloride ð71IZV050Ł and by the 0\2\3!selenadiazole "013#\ whichis formed by addition of a hydrazonyl chloride to the C1Se bond of a selenamide ð89ZOR0018Ł[

(123)

NO2

NO2

SePh

NSe

NN

Ph

O

Ph

(124)

5[93[0[1 Functions Bearing Chalcogen and P\ As\ Sb or Bi

5[93[0[1[0 Functions bearing oxygen and P\ As\ Sb or Bi

"i# Functions bearin` two oxyèn and one phosphorus substituent

Ortho!esters and amide acetals may be converted into phosphorus containing functions bytreatment with a phosphorus"III# nucleophile ð75MI 593!90Ł[ A 1!trimethylammonium!0!2!dioxane"014# reacts with isopropyl diphenylphosphinate to give the phosphine oxide "015# "Equation "8##ð77JOC2598Ł[ Similarly\ triethyl phosphite combines with 1!trimethylammonium!0\2!dioxolanea}ording the phosphonate ester ð63JPR802Ł[ Chlorodiphenylphosphine and dichloromethyl!phosphine react with ortho!formate esters to give the phosphine oxides "016# and phosphonateesters "017#\ respectively ð72TL0292\ 78T2676Ł[ Related reactions with hypophosphorous acidð79AJC176Ł and with diethyl phosphinate ð66TL1876Ł have been reported[ Triethyl phosphite\ incombination with phosphorus trichloride and zinc chloride\ reacts with triethyl ortho!acetate toform the phosphonate diester acetals "018# ð62S436Ł[ The adduct "029# formed from phosphorustrichloride and acetaldehyde reacts with triethyl ortho!formate to give the mixed phosphonate diesteracetal "020# ð89CC0022Ł[

O

O

N+Me3

O

O

PPh2

O

+

(125) (126)

(9)Ph2P OPri

(127)

Ph2P

OR

OR

OP

OR

OR

O

Me

OEt(128)

P

OEt

OEt

O

EtO

OEt(129)


(130)O

PCl2

Cl

(131)

OP

Cl

OMe

OMe

O

MeO

Dialkyl phosphinates react with the 2!acetylcoumarin to give the hemiacetal "021# ð80PS"46#100Ł[Hydration of a!phosphono!a!oxo esters "022# proceeds in high yield to give the hydrates "023^R�H#[ Similarly\ alcohols yield the corresponding hemiketals "023^ R�alkyl# "Scheme 19#[ Theyield is higher for methanol than for t!amyl alcohol as branching leads to steric congestion at thequaternary centre ð78CC135Ł[ 1\1!Dimethylpropylidynylphosphine "024# undergoes a double 0\2!dipolar cycloaddition with 3!chlorobenzonitrile oxide to yield the bicyclic product "025# ð73CC0523Ł[

O O

O

O

O

OH

PO(OR)2

(132)

H2O or ROH(Et2O)P CO2Et

O

O

(Et2O)P CO2Et

O

HO OR

HOP(OR)2

(133) (134)

Scheme 20

(135)

PBut

P

NO

ON

Ar

Ar

But

(136) (Ar = 4-ClC6H4)

Functions which already contain two oxygens and a phosphorus can be elaborated further at thephosphorus atom by standard methods[ Phosphinite acetals "026# undergo an Arbuzov reactionwith alkyl iodides "Equation "09## ð77PS"24#218Ł\ and the trimethylsilyl group of the phosphinites"027# is lost in the Arbuzov reaction with alkyl chloroformates which gives the phosphinates "028#ð75ZOB1316Ł[ Examples of aminoalkylation of phosphorus are also known ð78JCS"P0#0208Ł[

P

OR2

OR2

O

R1O

R3

(137)

(R1O)2P

OR2

OR2

R3I(10)

P

OR2

OR2

(138)

TMS-O

R1O

P

OR2

OR2

O

R1O

R3O2C

(139)

"ii# Functions bearin` one oxy`en\ one phosphorus and one nitro`en substituent

Electrochemical oxidation of the a!acylamino phosphonate "039# in methanol with a carbonanode gives the methoxylated compound "030# "Equation "00## ð78T0580Ł[ In an unexpected reaction\


the phosphonate "031# is generated from the treatment of the tosylate "032# with sodium diethyl!phosphinite ð82HCA1396Ł[

(140)

Ph NH

P(OEt)2

O

O(141)

Ph NH

P(OEt)2

O

O

OMeMeOH, NaCl

C anode(11)

N

O

O(EtO)2P

O(142) (143)

N

O

O

OTs

"iii# Functions bearin` one oxy`en and two phosphorus substituents

Double addition of phosphinic acids and phosphites to activated carboxylic acid derivativessuch as acid chlorides and anhydrides leads to a\a!diphosphino and a\a!diphosphono alcohols\respectively ð45JA3349\ 56JCS"C#0436\ 60JOC2732\ 62ZAAC"288#0\ 66TL0954\ 67CC174\ 68S70Ł[ An example ofthe reaction sequence is shown in Scheme 10[ Carboxylic acids combine with phosphorus trichloridebisphosphonic acids ð61MI 593!90\ 71MI 593!90Ł^ thus\ acetic acid gives MeC"OH#ðPO"OH#1Ł1[ Reactionof chlorodiphenylphosphine with acetic acid and then with acetic anhydride a}ords the bisphosphineoxide "033^ R�H# via the intermediate ketone "034# "Scheme 11#[ The acetylated analogue "033^R�Ac# is obtained after prolonged reaction times ð66JCS"P0#0787Ł[ Products analogous to "033^R�H# have also been obtained by hydrolysis of acylphosphine oxides ð67ZN"B#738Ł[

Ph Cl

O

Ph P(OMe)2

O

O

P(OMe)2

P(OMe)2HO

Ph

O

O

(MeO)3P HPO(OMe)2

Scheme 21

PPh2

PPh2RO

O

O

Ph2P

O

Ph2PH

OPh2PCl

AcOH Ac2O Ph2PH

O

(145) (144)

Scheme 22

O

The diazophosphonate "035# reacts with cyclohexenol in the presence of rhodium acetate to givethe ether "036# "Equation "01## ð81JOC067Ł[ Photochemical oxidation of a!diazophosphonates inmethanol leads to the formation of products of an analogous type ð71JOC0173Ł[ Cycloaddition ofthe silylnitronate "037# to the vinylbis"phosphonate# "038# leads to the formation of the dihy!droisoxazole "049# "Equation "02## ð81PS"58#64Ł[ Oxygen functions can also be introduced by reactionwith hydrogen peroxide\ as shown in Scheme 12 ð78JOC3161\ 82JOC3048Ł[

(MeO)2P P(OMe)2

O O

N2

O

(MeO)2P P(OMe)2

O O

OH, Rh2(OAc)4

(146) (147)

(12)


(EtO)2P P(OEt)2

O O

(148) (149) (150)

Ph

(13)TMS-O

N+

O–

+N

Ph

O P(OEt)2

P(OEt)2

O

O

O

P(OH)2

O

P(OH)2

O

P(OH)2

O

P(OH)2HO

HO

Na2CO3, H2O2, Na2WO4

H2O2, NaHCO3

O

P(OR)2

O

P(OR)2

O

P(OR)2

O

P(OR)2O

Scheme 23

"iv# Functions bearin` two oxy`en and one arsenic substituent

The cycloaddition of the benzoxarsole "040# to tetrachloro!o!benzoquinone gives a product "041#bearing this array of functional groups "Equation "03## ð72TL4370Ł[

O

As

O

AsO

O

Cl Cl

Cl

Cl

But

O

O

Cl

Cl

Cl

Cl

But +

(151) (152)

(14)

5[93[0[1[1 Functions bearing sulfur and P\ As\ Sb or Bi

"i# Functions bearin` one sulfur\ one oxy`en and one phosphorus substituent

Removal of an acidic proton from a!oxygen substituted phosphonic acid derivatives gives theopportunity for reaction with electrophilic sulfenylating reagents[ Diethyl a!methoxy phosphonate"042# when treated sequentially with a mixture of n!butyllithium and potassium t!butoxide\ elementalsulfur and iodomethane gives the methylthio product "043# ð65TL366Ł[ The use of n!butyllithiumalone gives compounds resulting from transesteri_cation ð68JOC1856Ł[ Similarly\ the a!sily!loxyphosphonate "044# reacts with LDA and diphenyl disul_de a}ording the trisubstituted product"045# ð67TL252Ł[ Activation of the a!carbon atom in a!"alkylthio#phosphonates can be achieved byhalogenation[ Treatment of the phosphonate "046# with N!chlorosuccinimide gives the a!chloroderivative "047# which\ in the presence of methanol\ is converted into the a!methoxy compound"048# "Scheme 13# ð74TL2368Ł[ The same substitution can be achieved using electrochemical oxidationin methanol ð76S33Ł\ and a similar halogenationÐsubstitution sequence takes place with sulfoxidesanalogous to "046# ð67JOC1407Ł[

1!Lithio!0\2!oxathiane reacts with dimethyl thiophosphonyl chloride to give the substitutionproduct "059# ð74JOC551\ 78JPO238Ł[ The ability of a sulfoxide to activate a neighbouring carbonatom is employed in the Pummerer rearrangement of a!sul_nyl phosphonates such as "050# in thepresence of acid anhydrides ð66S070\ 67JOC1407\ 75BCJ2182Ł[ In a reaction analogous to that of thediazo compound "035# the ether "051# is formed from the rhodium catalysed solvolysis of the a!diazophosphonate "052# in 1!propanol "Scheme 14# ð81SL864Ł[ Oxygen substitution can also beachieved by photolysis ð71JOC0173Ł[


(EtO)2P OMe

O

(EtO)2P OMe

O

SMe

(EtO)2P Ph

O

O-TMS

(EtO)2P Ph

O

SPhO-TMS

NCS, CCl4 MeOH(EtO)2P SMe

O

(157)

(EtO)2P SMe

O

(153)

(158)Cl

(154)

(EtO)2P SMe

O

(155)

i, LDAii, (PhS)2

i, BunLi, ButOK ii, S8iii, MeI

(159)OMe

(156)

Scheme 24

P(OEt)2

SS

O

Li

S

O

(EtO)2P SMe

O

(EtO)2P SMe

O

OAc

O

(163) (162)

P(OEt)2PhO2S

O

Ac2O, MeSO3H

(160)

Me2PSCl, THF

OPri

(161)

P(OEt)2PhO2S

O

N2

Rh2(NHCOCF3)4PriOH

Scheme 25

"ii# Functions bearin` two sulfur and one phosphorus substituent

0\2!Dithianes and 0\2!dithiolanes substituted at the 1!position with leaving groups can react withtriphenylphosphine ð66TL774\ 70S42Ł\ to give phosphonium salts such as "053# and "054#[ Similarly\trialkyl phosphites undergo Arbuzov reactions forming phosphonate diesters such as "055# "Equa!tion "04## ð66TL774\ 67JPR144\ 79S016\ 75MI 593!91Ł[ The alternative approach\ the reaction of 1!lithio!0\2!dithiane with an electrophilic phosphorus species\ chlorodiphenylphosphine ð75T0852\80JOC4808Ł or diethyl chlorophosphonate ð67S298Ł\ has also been reported[ Phosphorus substituentscan also be introduced by nucleophilic addition\ as with the benzo!0\2!dithiolium salt "056# ð65TL2584\89CC369\ 80JCS"P0#046Ł[ Reaction of the dithiocarbonate "057# with trialkyl phosphites generates thephosphonates "058# ð64JOC1466Ł[

S

S

PPh3 Cl–

(164)

+PPh3 BF4

–

(165)

+S

S

S

S

Cl

S

S

P(OEt)2

OP(OEt)3, Et3N

(166)

(15)


BF4–

S

S+

(167) (168)

S

SNC

NC

O

(169)

S

SNC

NC

P(OR)2

O

Sulfur functionality can be introduced into phosphorus!containing compounds by nucleophilicdisplacement of chloride by thiols\ in a manner analogous to that in which "047# is formed from "046#ð77SC0500Ł[ More commonly\ sulfur is introduced as an electrophile[ Sulfenylation of phosphorusstabilised carbanions is a useful general method for the formation of compounds containing twosulfurs and phosphorus[ A further sulfur substituent can be introduced into a species containingone sulfur and one phosphorus substituent\ as in sulfenylation of the ylide Ph2P1CHSPh ð89TL3248Łand of the phosphonate Ph1POCH1SPh ð66JCS"P0#1152\ 79S016Ł[ Alternatively\ both sulfur substituentscan be introduced by sequential sulfenylation^ two examples are shown in Scheme 15 ð77S451\81SC0248Ł\ and other examples are known ð74JCS"P0#1474Ł[

PPh2

NPh

PPh2

NPh

SMe

PPh2

NPh

MeS SMe

i, LDA, THFii, (MeS)2

i, LDA, THFii, (MeS)2

CO2Et(EtO)2P

O

SMeMeS

CO2Et(EtO)2P

O Al2O3-KF, MeSSO2Memicrowave

Scheme 26

S!Methyl "diisopropoxyphosphonyl#dithioformate "069# reacts with carbon nucleophiles on sulfurto give S!alkylated products such as "060# "Equation "05## ð76JCS"P0#070\ 78TL2304Ł[ A similar attackon sulfur occurs with thiols ð81JOC3496Ł[

SMe(PriO)2P

O

S

(170)

SMe(PriO)2P

O

(171)

S P(OEt)2

O

F F

(EtO)2POCF2Li(16)

Trialkylphosphines add to carbon disul_de to give zwitterionic adducts "061#[ These will undergocycloaddition with acetylenedicarboxylic esters leading to the ylides "062# ð64CC859\ 65BCJ0885\68JOC829\ 80JOC0705Ł[ Benzyl thiol reacts with the bisisothiocyanate "063# to give the symmetricalproduct "064# arising from double cyclisation ð81HAC004Ł[ Similar compounds are obtained by thetreatment of compound "065# with acid chlorides with aluminum trichloride catalysis[ The product"066# is a result of a carbon for phosphorus replacement[ Oxidation with hydrogen peroxide givesthe phosphine oxide "067# "Scheme 16# ð89JCS"P0#08Ł[

Preformed diethyl a\a!bis"methylthio#phosphonate undergoes lithiation and subsequent 0\1!addition on to a\b!unsaturated aldehydes and ketones to give the alcohols "068# "Equation "06##ð81T7586Ł[ The phosphine sul_de "079# can be methylated with methyl tri~ate to give the S!methyl!phosphonium salt\ which on reaction with HMPA is reduced to the corresponding phosphineð80TL6218Ł[

O

(EtO)2PR1

COR1+O

(EtO)2P

(179)

(17)

SMe

SMe

Li

R2

MeS SMeOH

R1


R13P

S

S–

CO2R2R2O2C SS

R2O2C CO2R2

PR13

PN

S S

NO

O

PSCN NCS

CHCl2

Ph SH

P

P

S S

P

S S

R13P + CS2

R

+

RCOCl, AlCl3 H2O2P

S S

–

+

(172) (173)

R

(174)

O

(175)

(176) (177) (178)

Scheme 27

(180)S

S

PPh2

S

"iii# Functions bearin` one sulfur\ one phosphorus and one nitro`en substituent

This functionality can be produced by reaction of suitably substituted carbanions with elec!trophilic sulfur reagents[ Compounds "070# ð81SC1270Ł and "071# ð74RTC066Ł are examples ofcompounds formed in this way\ by sulfenylation a! to phosphorus[ The same type of sulfenylationcan be achieved starting with a haloalkane and elemental sulfur ð71TL802Ł[ A di}erent method isthe addition of a nucleophilic phosphorus reagent to a thioimidate\ as in the conversion of thethioimidate "072# into "073# with sodium diethyl phosphite ð67JCR"S#30Ł[ The same product can beformed by addition of methylmagnesium iodide to the C1N bond of compound "074# "Scheme 17#ð64S674Ł[

(181)

Ph NH

PPh2

O SMe

O(182)

(EtO)2P

O

NC

SR

NCO2Et

MeS

O

(EtO)2P NHCO2Et

SMe NCO2Et

MeS

(EtO)2P

O

(184)

(EtO)2PO–Na+ MeMgI

(185)(183)

Scheme 28

Diazomethane undergoes cycloaddition with the vinyl sulfone "075# yielding initially the dihy!dropyrazole "076# "Equation "07## ð74CL0988Ł[


(187)

O

(EtO)2P

(186)

SO2Me

Ph

NN(EtO)2P

MeO2S

O

CH2N2(18)

Ph

"iv# Functions bearin` one sulfur and two phosphorus substituents

The sulfenylation of carbanions a! to phosphorus is used to produce this type of compoundð79S016\ 89H"29#744Ł^ an example is the bis"phosphonate# "077# ð79S016Ł[ Trialkyl phosphites reactwith thiophosgene to give compounds containing this functionality "Scheme 18# ð77PS"39#0Ł[ Arelated reaction has also been reported ð89TL0040Ł[

O

(EtO)2P

SPh

P(OEt)2

O

(188)

O

(RO)2P

S

P(OR)2

O

P(OR)2

O

O

(RO)2P

S

P+(OR)3 Cl–

P(OR)2

O

(RO)3P + CSCl2∆

Scheme 29

5[93[0[1[2 Functions bearing selenium and P\ As\ Sb or Bi

"i# Functions bearin` one selenium\ one sulfur and one phosphorus substituent

Selenylation of the anion of the a!sul_nylphosphonate "078# can be accomplished with phenyl!selenyl bromide "Equation "08## ð81TA0404Ł[ Similar selenylations can be achieved using seleniumand iodomethane ð70TL2986Ł[ Phenylselenyl chloride also adds to the phosponium ylide Ph2P1CHSPh ð72CB0844Ł[ Alternatively\ a compound with this functionality is formed by addition oftrimethyl phosphite to the heterocyclic cation "089# ð89CC369\ 80JCS"P0#046Ł[

S

O

(EtO)2P

O

S

O

(EtO)2P

O

PhSe i, BunLi

ii, PhSeBr(19)

(189)

Se

S+

(190)

"ii# Functions bearin` two selenium and one phosphorus substituent

Reaction of diethyl methylphosphonate with LDA and then with phenylselenyl bromide givesthe diselenated product ð81TL4264Ł[ In a similar fashion\ double selenation of the ylide Ph2P1CHMehas been observed ð68CB244Ł[ Trialkyl phosphites add to 0\2!diselenonium cations in a manner


analogous to that with the cation "089# ð77HCA0131\ 81TA0404Ł^ a similar reaction is known withtributylphosphine ð73TL3116Ł[ The a!diazophosphonate "081# undergoes insertion into the diselenoheterocycle "080# in the presence of boron tri~uoride etherate "Equation "19## ð80TL3078Ł[

Se

Se

Se

SeP(OMe)2

O

N2 P(OMe)2

O

+BF3•Et2O

(191) (192)

(20)

5[93[1 FUNCTIONS CONTAINING CHALCOGEN AND A METALLOID AND POSSIBLYA GROUP 04 ELEMENT

5[93[1[0 Functions Bearing Chalcogen and Boron

No compounds in this category have been noted[ It is possible\ however\ that the anion whichcan be formed from a!phenylthioalkylboronic esters "082# ð67JA0214Ł could react with a range ofsulfur\ selenium and phosphorus electrophiles[

OB

O

R1

PhS

(193)

5[93[1[1 Functions Bearing Chalcogen and Silicon

5[93[1[1[0 Functions bearing oxygen and silicon

"i# Functions bearin` two oxy`en and one silicon substituent

Silyl ketals such as "083# are produced from the reaction of alkyl benzoates with TMS!Cl\magnesium and HMPA ð60JOM"15#072\ 68JOC319Ł[ Silylated hemiketals are also accessible from theTMS!Cl\ magnesium and HMPA reagent combination ð60JOM"15#072Ł[ Acetals with a su.cientlyacidic a!hydrogen atom can be deprotonated and silylated using TMS!Cl ð80T2060Ł[ An alternativeapproach is to form acetals from silyl ketones such as "084# "Scheme 29# ð58CJC3236\ 79TL0246\89JA0851Ł[

O

Ph OMePh

OMe

TMS

O-TMS

(194)

O

Ph SiPh3

O O

Ph SiPh3

HOOH

TMS-Cl, Mg, HMPA

, BF3, Et2O

(195)

Scheme 30

Oxidation of compounds containing a vinylsilane moiety provides another route into functionsbearing two oxygens and a silicon[ Treatment of a highly strained 0!trimethylsilylcyclopropenederivative "085# with excess mcpba leads to the formation of the epoxide "086# ð75TL4032Ł[ Oxidationof the compound "087# containing two furan rings with singlet oxygen selectively gives the product"088# resulting from cycloaddition to the silylated ring ð89TL6190Ł[ Two other methods starting fromvinylsilanes are the rearrangement of the trimethylsilylallene "199# to the dihydrofuran "190#ð71TL298Ł and the addition of dichlorocarbene to 1!trimethylsilyldihydrofuran "191# and sub!sequent reaction with methanol ð73JOM"154#126Ł[ 0!Ethoxy!0!trimethylsilylallene also undergoes

014Chalcoèn and a Metalloid

cycloaddition with enones at the substituted double bond to give products containing this func!tionality "Scheme 20# ð80CB0314Ł[

TMS

TMS

OCHO

O

OCHO

TMS

O O

TMS

O O

O

O

TMS

O

HO

TMSMeO

•

TMS

OMe

O O

TMSCl

TMS

Cl

mcpba

(197)(196)

1O2

O

Cl

TMS

OMe

(198)

(200)

(199)

(201)

:CCl2 MeOH

(202)

Scheme 31

The disilene "192# and methylfuran!1!carboxylate give a ð1¦1Ł cycloaddition product "193#[ Thisreaction is particular to the methyl ester\ higher homologues failing to react "Equation "10##ð80OM2355Ł[

Si SiAr

Ar Ar

Ar O CO2Me OMeO

Si

SiO

ArAr

ArAr

+

(203) (204)

(21)

"ii# Functions bearin` one oxyèn\ one phosphorus and one silicon substituent

Deprotonation of the a!"trimethylsilyloxy#phosphonate ester "194# with LDA and quenching withTMS!Cl gives the silylated adduct "195# ð70CC858Ł[ Quenching of the lithiated intermediate generatedfrom the a!substituted!a!trimethylsilyloxy phosphonate "196# a}ords some of the alcohol "197#by Wittig rearrangement in addition to recovered starting material ð68TL3364\ 71BCJ113Ł[ The a!diazophosphonamide "198# reacts with aldehydes to yield epoxides "109# "Scheme 21# ð78AG506\80NJC282Ł[

"iii# Functions bearin` one oxyèn and two silicon substituents

Two silicons can be introduced into a variety of carboxylic acid derivatives by reaction withTMS!Cl and Group 0 or Group 1 metals "Equation "11##[ The addition of HMPA and the use ofcoordinating solvents often leads to improved yields[ Thus\ primary amides react in the presence oflithium ð68JOM"066#026Ł^ carboxylic acids ð65TL0480Ł\ esters ð67BCJ1280Ł and silyl ketones ð65TL0480Łutilise sodium while silyl ketones ð78JOC4502Ł and acid chlorides ð61JOM"28#C38Ł are converted withthe addition of magnesium[ Other reactions of this type which have been described include theaddition of triphenylsilyllithium to ethyl formate ð57CJC1008Ł and the interaction of methyl benzoatewith aluminum chloride and tris"trimethylsilyl#aluminum ð70AG"E#470Ł[


TMS-O P(OEt)2

O

TMS-O P(OEt)2

O

TMS

TMS-O P(OEt)2

O

Ph

TMS P(OEt)2

O

Ph OH

(PriNH)2P TMS

O

N2

(205)

(209)

(PriNH)2P TMS

O

i, LDAii, TMS-Cl

(207)

(206)

(210)

OR

i, LDAii, H2O

(208)

heat, RCHO

Scheme 32

O

R XR

TMS

TMS

O-TMSTMS-Cl, M

(22)

Triphenylsilylsilyloxirane can be deprotonated with n!butyl lithium at the substituted carbonatom[ Quenching of the intermediate with TMS!Cl a}ords the bis"silyl#oxirane "100#[ 0\0!Bis"tri!methylsilyl#ethene undergoes 0\2!dipolar cycloaddition with benzonitrile oxide giving the dihy!droisoxazole "101# ð72JOC2078Ł[

OPh3Si

TMS(211) (212)

ON

TMSTMS

Ph

5[93[1[1[1 Functions bearing sulfur and silicon

"i# Functions bearin` one sulfur\ one oxy`en and one silicon substituent

The acidity of the proton located on a methylene or methyne unit between a sulfur and anoxygen facilitates deprotonation and subsequent quenching with activated silyl compounds[ Prop!0!enyloxathiane "102#\ on treatment with s!butyllithium and TMS!Cl gives the a!silylated product"103# "Equation "12## ð81T1490Ł[ The acidity of the proton is increased when the sulfur atom ispresent at its highest oxidation state\ i[e[\ as a sulfone\ when n!butyllithium will su.ce to causereaction ð68TL2264\ 77CC534\ 89TL0766\ 80JCS"P0#786Ł[

S

O

(213)

S

O

(214)

TMS

i, BusLiii, TMS-Cl

(23)

Once formed\ these silylated compounds can undergo further deprotonation and alkylation[ Thus\1!trimethylsilyl!0\2!oxathiane "104# is methylated after treatment with s!butyllithium "Equation "13##ð74JOC551Ł[ Other alkylations of this type are known ð74TL1564\ 76JAP5150876\ 76TL1036\ 78JOC4992\81JAP3038042Ł[


(215)

i, BusLiii, MeIO S

TMS

(24)O S

TMS

Cycloadditions o}er a further route into this trisubstituted functionality[ Phenyl trimethylsilylthioketone\ which can be generated by the rearrangement of 1!phenyl!1!silylthiirane\ ð56JA320Ł willreact with nitrile oxides ð70CC711\ 89H"20#36Ł\ a!nitrosostyrene ð74TL1020\ 76JCS"P0#1536Ł and silylenones ð80TL1860Ł to a}ord cyclic products "Scheme 22#[

STMS

Ph Ph TMS

S

ON

SPhTMS

Ph

S

ON

Ph

O

S

TMS

TMS

Ph

TMS

Ph

PhCNO

Ph NO

O

TMS

Scheme 33

"ii# Functions bearin` two sulfur and one silicon substituent

Bis"alkylthio#methanes such as "105#\ on treatment with base and on subsequent addition of asilylating agent o}er facile access to both tertiary "106# ð64ZAAC"307#197\ 89CL0300\ 89JOM"277#36\80TL5790Ł and quaternary ð66JOC0556\ 74S587\ 75HCA33\ 75JCS"P0#084\ 77ZOB0955Ł bis"alkyl!thio#trialkylsilylmethanes "Equation "14##[ The preferred reagent for deprotonation is n!butyl!lithium\ and trialkylsilyl chlorides are used most often to quench the lithiated intermediate[ Theseconditions are general enough to allow silylation at hindered positions ð75HCA33Ł[ The presence ofTMEDA can lead to higher yields ð77ZOB0955Ł[ Dichlorodimethylsilane has been demonstrated toundergo double substitution of chloride by 1!lithio!1!methyl!0\2!dithiane ð56JA323Ł[

EtS SEt EtS SEt

TMS i, BuLiii, TMS-Cl

(25)

(216) (217)

With 1!allyl substituted 0\2!dithianes\ the lithiated intermediate conceivably could be silylated ateither the a! or the g!position of the allyl substitutent[ It is found that silylation usually occursmainly at the a!position\ even when this leads to the more sterically congested of the two possibleproducts "Scheme 23# ð68TL0716\ 79JCS"P0#1567\ 75HCA0267\ 76JOC744Ł[ In the case of the dithianederivatives "107#\ deprotonation by LDA and silylation takes place a! to the ring for R�Me but atboth the a! and the g!positions for R�Ph ð77JCS"P0#2256Ł[

S

SPh

S

SPh i, BuLiii, TMS-Cl

TMS

Scheme 34

S

S

SR

(218)


Products which contain sulfur in a higher oxidation state can be accessed by the use of startingmaterials at the required level of oxidation[ Thus\ the sulfone "108# reacts with trialkylsilyl per!~uorobutanesulfonates and two equivalents of n!butyllithium to give the products "119# "Equation"15## ð82CB426Ł[ Alternatively\ oxidation can be performed on the silylated compound ð65JOC2864Ł[

(219)

S

S

OO

O O(220)

S

S

OO

O O

R3Si SiR3

C4F9SO3SiR3(26)

There are many examples of the lithiation of bis"alkylthio#trimethylsilylmethanes and reactionwith electrophiles to generate quaternary products "Equation "16##[ Alkylations have been performedwith iodoalkanes ð79JA5050\ 80TL1710Ł with the optional addition of HMPA ð73HCA0623Ł[ Thesulfone "119^ R�Me# is methylated with methyl per~uorobutanesulfonate after deprotonation withtwo equivalents of n!butyllithium ð80CB0794Ł[ Acetylation of 1!trimethylsilyl!0\2!dithiane has beenaccomplished by the use of acetyl chloride ð62JCS"P0#1161Ł[ Michael addition of lithiated bis"phen!ylthio#! ð78JOC0189Ł and bis"methylthio#! ð66CB730Ł trimethylsilylmethanes occurs with cyclo!pentenone^ the bis"methylthio# intermediate also adds 0\3! to t!butyl cinnamate ð74TL2920Ł[1!Lithio!1!trimethylsilyl!0\2!dithiane undergoes 0\1!addition to cyclohex!1!enone but addition ofHMPA to the reaction mixture promotes 0\3!addition ð68CC099Ł[

(27)R1S SR1

LiTMS

R1S SR1

R2TMSR2X

"iii# Functions bearin` one sulfur\ one nitro`en and one silicon substituent

The examples of compounds falling into this class in the literature are formed exclusively bycycloaddition[ The thioketone "110# reacts with diazomethane to give the dihydro!0\2\3!thiadiazole"111# ð80MI 593!90Ł[ A dihydro!0\2\3!thiadiazole "112# is obtained from the treatment of thioketone"113# with the hydrazonyl chloride "114# in the presence of triethylamine ð89H"20#36Ł[ The tri!methylsilylallene "115# undergoes a ð1¦1Ł cycloaddition with chlorosulfonyl isocyanate leading tothe b!lactam "116# "Scheme 24# ð74TL4990Ł[

S

But TMSNN

S

But

TMS

S

Ph TMSNN

S

Ph

TMS

Ph

Ph

i, CSIii, Na2SO3

•

TMS

SAr

(224)

(221)

NH

TMS

SAr

O

PhCH(Cl)=NNHPh (225), Et3N

(222)

CH2N2

(223)

(226) (Ar = 4-ClC6H4) (227)

Scheme 35


"iv# Functions bearin` one sulfur\ one phosphorus and one silicon substituent

Pairwise combinations of sulfur\ phosphorus and silicon attached to the same carbon atom willall activate the carbon atom towards anion formation or radical halogenation[ The introduction ofthe remaining element as an electrophile or nucleophile\ as appropriate\ will allow the formation ofthe complete functional group[ Thus\ deprotonation of diethyl "methylthio#methylphosphonate ordiethyl "trimethylsilyl#methylphosphonate with n!butyllithium and quenching with TMS!Cl or withdimethyl disul_de\ respectively\ leads to the same trisubstituted product "Scheme 25#[ The samecompound can be prepared by the radical bromination of trimethylsilyl"methylthio#methane andsubsequent Arbuzov reaction with triethyl phosphite[ Of these reactions\ the silylation confers thebest yield ð78S090Ł[ 0\2!Dipolar cycloaddition of nitrile sul_des to the silylated phosphaalkene "117#and subsequent elimination of a nitrile leads to the formation of the three!membered ring species"118# "Scheme 26# ð78TL3490Ł[ An alternative route to this ring system has been described ð76TL5010Ł[

i, BunLi; ii, TMS-Cl(EtO)2P SMe

O

i, BunLi; ii, Me2S2(EtO)2P TMS

O

TMS SMe i, NBS

ii, P(OEt)3

(EtO)2P SMe

O

TMS

Scheme 36

R N S+

–

P

Ph TMS

Cl

N

P

S

R

ClTMS

Ph

P S

TMSPh

Cl

Scheme 37

– RCN

(228) (229)

"v# Functions bearin` one sulfur and two silicon substituents

Treatment of phenylthio"trimethylsilyl#methane sequentially with n!butyllithium and TMS!Clgives phenylthiobis"trimethylsilyl#methane[ This can be alkylated by the addition of further n!butyllithium and an alkyl halide ð80T504Ł or it can be oxidised to the sulfone with peroxybenzoicacid ð73JOC4976Ł "Scheme 27#[ Examples of double silylation by TMS!Cl of a carbanion adjacent toa sulfone function are also known ð78LA864Ł[ More bulky silylating agents such as triethylsilylchloride give selective monosilylation ð78TL1762Ł[

Scheme 38

PhS TMS

i, BunLi

ii, TMS-Cl PhS TMS

TMS

i, BunLi

ii, BrC3H6Ph PhSPh

PhCO3HPhSO2 TMS

TMS

TMSTMS

The cycloaddition of the thiocarbonyl ylide "129# to dipolarophiles such as methyl acrylate"Equation 17# ð76CPB0623Ł and acrylonitrile ð75H"13#0460Ł gives bis"trimethylsilyl# substitutedtetrahydrothiophenes[ The alkene "120# undergoes thermal isomerisation to the bis"trimethylsilyl#thiirane "121# "Equation "18## ð76CL1066Ł[

TMS

TMS

S CH2+ –

X

S

X

TMS

TMS

S TMS

TMS

X

+

(230) (X = CN, CO2Me)

(28)


(231)

(29)

S

Ph

PhTMS

TMS

S

TMS

TMS Ph

Ph

∆

(232)

5[93[1[1[2 Functions bearing selenium and silicon

"i# Functions bearin` one selenium\ one sulfur and one silicon substituent

Deprotonation of methyl phenyl sulfone with LDA and reaction of the carbanion with TBDMS!Cl gives the silylated product[ Addition of a further equivalent of LDA and conversion to thecuprate can be followed by reaction with selenocyanogen to give the selenocyanate "122# ð76TL4010\77JA7560Ł[ 0!Benzenesulfonyl!0!trimethylsilylalkenes such as "123# undergo Michael addition byalkyllithium reagents and the resultant lithiated species can be quenched with phenylselenyl chloride"Scheme 28# ð70TL3176\ 73TL1910Ł[

PhSO2 SiMe2ButPhSO2 SiMe2But

SeCN

O

TMS

PhSO2

OMe

O

TMS

PhSO2

OMe

i, LDA ii, CuCN

iii, (SeCN)2

PhSO2Me

i, LDAii, TBDMS-Cl

PhSe

(233)

i, MeLiii, PhSeCl

(234)Scheme 39

"ii# Functions bearin` one selenium and two silicon substituents

Reaction of a!trimethylsilyl!a!phenylselenyltoluene "124# with LDA and TMS!Cl gives theproduct "125# bearing two trimethylsilyl groups "Equation "29## ð66JOC0662Ł[

i, LDAii, TMS-ClPhSe Ph

TMS

(235) (236)

(30)Ph

TMS

TMS

SePh

5[93[1[2 Functions Bearing Chalcogen and Germanium

5[93[1[2[0 Functions bearing oxygen and germanium

"i# Functions bearin` two oxy`en and one `ermanium substituent

Only one example of this functional group has been reported[ Reaction of the ketal "126# withtrimethylgermyl chloride gives the substitution product "127# "Equation "20## ð72CC128\ 72T2962Ł[

Li

TMS

(238)

Me3GeClOO

(237)

(31)GeMe3

TMS

OO


"ii# Functions bearin` one oxyèn\ one nitroèn and one èrmanium substituent

One class of compound has been noted with this grouping[ Treatment of dimethylamides withtriethylgermyllithium gives the O!lithiated intermediates "128# resulting from addition to the car!bonyl group[ On workup\ these intermediates are converted into the ketones "139# "Scheme 39#ð72JOM"137#40\ 77JOM"230#182\ 77JOM"237#206Ł[

O

R NMe2 R NMe2

GeEt3LiO O

R GeEt3

Scheme 40

(239) (240)

Et3GeLi

"iii# Functions bearin` one oxyèn\ one phosphorus and one èrmanium substituent

Addition of dimethyl"trimethylgermyl#phosphine to phenyl trimethylsilyl ketone generates the O!silylylated product "131#[ This is believed to be obtained via the O!germyl isomer "130# "Scheme 30#ð66JOM"030#24Ł[

Scheme 41

O

Ph TMS

(241) (242)

Me3GePMe2 + Ph

PMe2

TMS

OGeMe3 Ph

PMe2

O-TMS

GeMe3

"iv# Functions bearin` one oxyèn\ one èrmanium and one silicon substituent

Treatment of phenyl triethylgermyl ketone "132# with triethylsilyllithium yields the alcohol "133#ð77MI 593!90Ł[ O!Alkylated functions such as "134# are accessible from the reaction of bromo!trialkylgermanes with lithiated trimethylsilylmethyl methyl ether[ These compounds can be furtheralkylated at the central carbon atom "Scheme 31# ð81SL732Ł[

(245)

MeO TMS

i, BusLi

ii, BrGeMe3MeO TMS

GeMe3

Scheme 42

O

Et3Ge Ph

(243) (244)

Et3SiLiPh

OH

GeEt3

SiEt3

"v# Functions bearin` one oxyèn and two èrmanium substituents

In a reaction analogous to that shown with triethylsilyllithium\ the ketone "132# reacts withtriethylgermyllithium to give bis"triethylgermyl# carbinol "135# ð76IZV1761\ 77MI 593!90Ł[ Ethyl for!mate reacts with triphenylgermyllithium to give a mixture of bis"triphenylgermyl#methanol "136#and its formate ester "137#[ The latter can be converted to the former by treatment with lithiumaluminum hydride ð57CJC1008Ł[


Ph

GeEt3

GeEt3

OH

(246)

Ph3Ge GePh3

(247)

OH

Ph3Ge GePh3

(248)

OCHO

5[93[1[2[1 Functions bearing sulfur and germanium

"i# Functions bearin` one sulfur\ one oxyèn and one èrmanium substituent

0\2!Oxathiane\ when reacted with s!butyllithium\ reacts with trimethylgermyl chloride to give the1!substitution product "138# "Equation "21## ð70TL1994\ 74JOC546\ 74JOC551Ł[

(249)

O

S i, BusLi

ii, Me3GeCl

O

S

GeMe3 (32)

"ii# Functions bearin` two sulfur and one èrmanium substituent

The reported preparations of these compounds are all the results of the formation of a carbanionbetween two sulfur atoms and quenching with an electrophilic germanium species[ 1!Lithio!0\2!dithiane has been reacted with triethylgermyl chloride ð57CJC1008Ł\ triethylgermyl bromide ð56JA320Łand triphenylgermyl bromide ð56JA320Ł to give products "149#[ Quaternary systems are also access!ible starting from 1!alkylated dithianes ð56JA320Ł[ Both 0\2\4!trithiane and 0\2\4\6!tetrathiocanecan be substituted in the same manner ð64ZAAC"307#197\ 65CB0128Ł[ The difunctional 0!gerana!0\0!dichloro!2!cyclopentene "140# reacts with two equivalents of 1!lithio!0\2!dithiane a}ording thequaternary germanium species "141# ð73JAP48082786Ł[ The bis"sulfone# "108# undergoes substitutionat both methylene groups by trimethylgermyl per~uorobutanesulfonate ð82CB426Ł[

(250)

S

S

GeR3

(251)

GeCl

Cl

(252)

Ge

S

SS

S

"iii# Functions bearin` one sulfur and two èrmanium substituents

The only example in the literature of compounds containing this grouping "142# is provided bythe reaction of methyl alkanesulfonates R0CH1SO2Me with trialkylgermyl halides and sodiumhexamethyldisilazide ð73ZOB0731Ł^ the reaction gives a mixture of products including "142#[

R1

GeR23

GeR23

SO3Me

(253)

022Chalco`en and a Metal

5[93[2 FUNCTIONS CONTAINING CHALCOGEN AND A METAL AND POSSIBLY AGROUP 04 ELEMENT OR A METALLOID

5[93[2[0 Functions Bearing Oxygen and a Metal

5[93[2[0[0 Functions bearing two oxygens and a metal

The 0\2!dioxane "143# reacts with n!butyllithium to generate the lithiated species "144# ð72T2962Ł[Further reaction with trimethyltin chloride a}ords the trimethylstannyl derivative "145# "Scheme32# ð72CC128\ 72T2962Ł[

O

O

TMS

O

O

Li

TMS

O

O

SnMe3

TMS

BuLi Me3SnCl

(254) (255) (256)

Scheme 43

5[93[2[0[1 Functions bearing oxygen\ silicon and a metal

Trimethylsilylmethyl methyl ether is lithiated at the methylene group by s!butyllithium ð78TL108Ł[The proton at the 1!position of 1!trimethylsilyloxiranes can be removed with retention of con!_guration by n!butyl! or s!butyllithium ð77JOM"230#182\ 78JOC3931Ł[ Further reaction with trimethyltinbromide gives the trimethylstannyl derivatives "146# "Scheme 33# ð78JOC3931Ł[

BusLi Me3SnBrO

H

TMSR

H

O

Li

TMSR

H

O

SnMe3

TMSR

H

Scheme 44

(257)

5[93[2[0[2 Functions bearing oxygen and two metals

Reaction of 1!"tributylstannyl#oxirane with n!butyllithium results in the formation of the 1!lithio!1!"trimethylstannyl#oxirane "147# "Equation "22## ð77JOM"230#182Ł[

(33)BuLi

(258)

O OBu3Sn

LiBu3Sn

5[93[2[1 Functions Bearing Sulfur and a Metal

5[93[2[1[0 Functions bearing sulfur\ oxygen and a metal

Functions bearing oxygen\ sulfur and lithium are generated as intermediates in reactions whichinvolve their subsequent reaction with electrophiles^ examples are provided by the reactions of 0\2!oxathianes "102# and "104# discussed in Section 5[93[1[1[1[ Sulfur can be present in any of itscommon oxidation states[ Lithiated compounds can also act as precursors to other metalled deriva!tives[ Treatment of 1!lithio!0\2!oxathiane with trimethyllead acetate results in the formation of


compound "148# by metal exchange ð70TL1994\ 74JOC546Ł[ Another approach to compounds withthese functional groups is exempli_ed by the reaction of tributylstannyllithium with the thion!olactone "159# and subsequent alkylation with iodomethane "Scheme 34# ð76JA1493\ 89JA2585Ł[

(259)

O

S

PbMe3

(260)

O

S

O

SnBu3MeS i, LiSnBu3ii, MeI

Scheme 45

5[93[2[1[1 Functions bearing two sulfurs and a metal

As with functions bearing oxygen\ sulfur and lithium\ lithiated derivatives are often used asintermediates\ generated in situ\ in the derivatisation at the carbon atom between two sulfur atoms[A range of strong bases such as the butyllithiums\ LDA\ lithium hexamethyldisilazide "LHMDS#and lithium phenylamide can be used in aprotic solvents at low temperatures to lithiate suchcompounds ð67JOC3124\ 67MI 593!90\ 70JOC0401\ 71JOC0034\ 75S522\ 89MI 593!90Ł[ In the lithiation of the0\2!dithiane derived from of 1\3!hexadienal\ reaction occurs exclusively at the 1!position ð81MI 593!90Ł[ Lithiated dithianes "151# are also available from the reaction of the dithioketene acetal "150#with alkyllithium reagents ð58TL062Ł[ Treatment of compounds bearing three phenylthio residuesattached to the same carbon atom with s!butyllithium leads to replacement of one of the heteroatomswith lithium ð73JOC594\ 74JOC2155Ł[ Exchange of trimethyltin for lithium has also been used toproduce a compound with this functionality "Equation "23## ð77BCJ1036Ł[

(261)

S

S

(262)

S

S

LiR

RLi(34)

Reaction of a dithioester with ethylmagnesium iodide results in addition to the C1S bond"Scheme 35# ð68JA3621Ł[

S

R SEtR

SEt

SEt

MgIEtMgI

Scheme 46

A variety of metallated 0\2!dithianes and related species can be prepared from the 1!lithiointermediate by metal exchange[ Thus\ the tris"isopropoxy#titanium derivative "152# can be formedby reaction with tris"isopropoxy#titanium chloride ð70HCA246Ł[ In a similar manner\ trialkyltin ortriaryltin derivatives can be obtained from 1!lithio!0\2!dithianes and !0\2\4!trithianes by reactionwith the appropriate trialkyltin chlorides or triaryltin chlorides ð64ZAAC"307#197\ 68PS"6#192\75JOM"292#078Ł[ Alternative routes to functions with two sulfur and one trialkyltin substituent areexempli_ed by the alkylation of 1!lithio!1!tributylstannyl!0\2!dithiane ð78TL04\ 89JA3441\ 81CJC1224Ł

S

S

Ti(OPri)3

(263)

024Chalco`en and a Metal

and by the conjugate addition of the intermediate "153# to cyclohexenone with the option ofalkylation of the generated lithium enolate "Equation "24## ð64AG26\ 66CB730Ł[

OO

Me3Sn

MeSMeS

R

Li

SMe

SMe

SnMe3

(264)

+RX

(35)

5[93[2[1[2 Functions bearing sulfur\ boron and a metal

a!"Phenylthio#alkylboronate esters such as "154# have been demonstrated to undergo lithiationwith LDA "Equation "25## ð67JA0214Ł[

(36)O

B O

O

B O

LDA

(265)

SPhSPhLi

5[93[2[1[3 Functions bearing sulfur\ silicon and a metal

a!"Trimethylsilyl#methyl sul_des and sulfones are readily metallated at the methylene group bybutyllithium ð75JCS"P0#084Ł[ Subsequent exchange reactions have been used to produce trialkyltinderivatives such as "155# ð75JCS"P0#084Ł and copper derivatives ð75JOC2872Ł[ An alternative route tolithiated species is the addition of alkyllithium reagents to vinylsilanes^ thus\ the intermediate "156#is produced from H1C1C"SPh#!TMS and methyllithium ð75JCS"P0#084Ł[ Multinuclear NMR studieshave demonstrated the conformational stability of the species "157# in etherÐTHF mixtures due toion pairing[ Addition of greater than three equivalents of HMPA causes a degree of racemisationto occur ð82AG"E#0358Ł[

SnBu3

PhS TMS

(266)

Li

SPh

TMS

Et

(267)

PhS

H

SiMe2Ph

Li

(268)

5[93[2[1[4 Functions bearing sulfur and two metals

Two tributyltin functions can be introduced on to a methylene group a! to a sulfone group bylithiation and reaction with tributyltin chloride ð81CC769Ł[

5[93[2[2 Functions Bearing Selenium and a Metal

5[93[2[2[0 Functions bearing selenium\ sulfur and a metal

LDA will lithiate "phenylthio#"phenylseleno#methane ð89JA4598Ł[

5[93[2[2[1 Functions bearing two seleniums and a metal

Bis"phenylseleno#methane can be lithiated with the hindered base LITMP and HMPA as acosolvent ð68JOM"066#0Ł[ As an alternative\ reaction of tris"methylseleno#methane with n!butyl!lithium results in replacement of one methylseleno group by lithium ð68TL2264Ł[


5[93[2[2[2 Functions bearing selenium\ phosphorus and a metal

Treatment of the a!"phenylseleno#methylphosphonate "EtO#1POCH1SePh with n!butyllithiumresults in lithiation at the methylene group ð76S058Ł[

5[93[2[2[3 Functions bearing selenium\ silicon and a metal

Lithium derivatives can be generated by hydrogenÐlithium exchange\ as in the generation of thespecies "158# from the corresponding allyl"phenylseleno#silane and lithium diethylamide ð64JOC1469Łor by exchange of a phenylseleno function for lithium\ as in the generation of the intermediate "169#from "160# and n!butyllithium "Scheme 36# ð67JOM"038#C09Ł[

PhSe

TMS

PhSe

TMSLi

LiNEt2

BuLi

(269)

(271) (270)

SePh

TMS

SePh

Scheme 47

SePh

TMS

Li


6.05Functions Containing at LeastOne Group 15 Element (and NoHalogen or Chalcogen)DAVID P. J. PEARSONZENECA Agrochemicals, Bracknell, UK

5[94[0 FUNCTIONS CONTAINING THREE GROUP 04 ELEMENTS 026

5[94[0[0 Functions Bearin` Three Nitroèn Atoms 0265[94[0[0[0 0\0\0!Triaminoalkanes 0265[94[0[0[1 0\0\0!Trinitroalkanes 0325[94[0[0[2 Mixed nitro and other functions 040

5[94[0[1 Functions Bearin` Three Phosphorus Atoms 0405[94[0[1[0 Introduction 0405[94[0[1[1 Functions bearin` tri! or pentavalent phosphorus 0405[94[0[1[2 Functions bearin` heptavalent phosphorus 043

5[94[0[2 Functions Bearin` Three Arsenic Atoms 0445[94[0[3 Functions Bearin` Three Antimony or Bismuth Atoms 0455[94[0[4 Functions Bearin` Nitroèn and Other Group 04 Elements 045

5[94[0[4[0 Functions bearin` two nitroèn atoms and one phosphorus atom 0455[94[0[4[1 Functions bearin` two phosphorus atoms and one nitroèn atom 0465[94[0[4[2 Functions bearin` nitroèn and other `roup 04 elements 050

5[94[1 FUNCTIONS CONTAINING GROUP 04 ELEMENTS WITH METALLOIDS 051

5[94[1[0 Functions Bearin` Group 04 Elements and Silicon 0515[94[1[0[0 Functions bearin` nitroèn and silicon 0515[94[1[0[1 Functions bearin` phosphorus and silicon 0525[94[1[0[2 Functions bearin` nitroèn\ phosphorus and silicon 0575[94[1[0[3 Functions bearin` arsenic\ antimony or bismuth 057

5[94[1[1 Functions Bearin` Group 04 Elements and Boron 0585[94[1[2 Functions Bearin` Group 04 Elements and Germanium 058

5[94[2 FUNCTIONS CONTAINING GROUP 04 AND METAL ELEMENTS\ AND POSSIBLYA METALLOID 069

5[94[0 FUNCTIONS CONTAINING THREE GROUP 04 ELEMENTS

5[94[0[0 Functions Bearing Three Nitrogen Atoms

5[94[0[0[0 0\0\0!Triaminoalkanes

"i# Introduction

Methods for the formation of compounds of general structure "0#\ commonly known as ortho!amides\ have been reviewed\ most recently bySimchen\ who has written two accounts ðB!63MI 594!91Ł

026

027 At Least One Group 04 Element

and ð74HOU"E4#2Ł\ but also by deWolfe ðB!69MI 594!92Ł and Kantlehner ðB!68MI 594!90Ł[ Each ofthese reviews is part of a more general treatment of ortho!acid derivatives but gives extensivereferences to their preparation[

R1

N

N

N

R3R2

R5

R4

R7 R6

(1)

As expected\ compounds of this type are moderate to strong bases "unless the nitrogen atomsare acylated# and dissociate to a signi_cant degree in solution as evidenced by the conductivitymeasurements of Bredereck ð58MI 594!90Ł "quoted in ðB!68MI 594!90Ł#[ This gives rise to their pro!pensity for elimination\ displacement and disproportionation reactions\ as shown in Scheme 0ð57CB40Ł\ and explains why examples from carboxylic acids higher than formic are relatively rare\why the amines involved are generally fully substituted and why the most common structural typehas three identically substituted nitrogen atoms[

R1

N

N

N

R3R2

R5

R4

R7 R6N

R1 NR3

R2

R5 R4

N

N

N

R3R2

R5

R4

R7 R6N

NR5

R4

R7 R6

+ HNR2R3R1

+

R1

–NR6R7

Scheme 1

This functional group occurs in some natural products\ e[g[\ oxaline "1# ð65T1514\ 79CPB1876Ł anddibromoagelaspongin "2# ð78T2376Ł[

N

N

OMe

O

NHMeO

O N NH

(2)

N

NHN

HN

HN

Br

Br

O

HO

(3)

"ii# Preparation

"a# From amidinium salts[ Formamidinium salts are reported by a number of authors to undergoreaction with secondary amines or their metal salts "Scheme 1#[ For example\ the sodium salts ofN!methylanilines react with a salt "3# to give the ortho!amides "4# in modest yield ð51JOC2553Ł[Lithium dialkylamides have been similarly used ð55AG"E#021Ł and this method was applied to thepreparation of unsymmetrical examples such as "5# ð57CB0774Ł[ Potassium t!butoxide has beenemployed as the base in a similar synthesis ð57CB2947Ł^ in this instance the reaction may occur bythe initial addition of the alkoxide moiety[ The unusual displacement of cyanide in Structure "6# ispresumed to occur via the intermediacy of an amidinium salt "7# ð68S231Ł[

"b# From other amide salts[ The Vilsmeier reagent "8# reacts with the potassium salts of saccharinand phthalimide to give the unsymmetrically substituted adducts "09# ð50CB2098Ł[ Bredereck et al[report the alkylation of N\N!diethylformamide "00# and its subsequent reaction with diethylamineto give "01# in low yield ð57CB2947Ł[ In previous studies by the same group triformamidomethane"03# was constructed from formamide via similar intermediates "02# "Scheme 2# and a comparison

028Three Group 04 Elements

MeN N

Me

Ar Ar

N

N NMe

Ar

Me

Ar

Me Ar

MeN N

Me

Me Me

N

N

N

Me Me

Me

MeMe

Me

N

N N

Et Et

Me

Me

Me

Me

N NMe

Me

Me

Me

N

N NMe

Me

Me

Me

+

(4)I–

–CN+

LiNMe2

73% N

N

N

Me Me

Me

MeMe

Me

(5)

Cl–

ArNHMe, NaH

Ar = Ph44%

+

42%

LiNMe2, Et2O–20 °C

LiNEt2, Et2O

(6)

63%

(7) (8)

Scheme 2

was made of various alkylating and acylating agents ð48CB218Ł[ When dialkyl sulfates were usedthe yield increased with the bulk of the alkyl group\ perhaps re~ecting the ease of the subsequentdisplacement step[

NMe

Me

(10)

Cl

N

N N

X

X

O

OMe Me

XNK

O

O NEt

EtO N

Et

Et

MeN

N NEt

Et

Et

Et

Et Et

O NH2 O NH

H

Cl–

Me+

+

MeSO4–

Me2SO4 HCONH2

36%

(13) (14)

N

N

H

O N O

H

O

H

+Me2SO4

(11)

(9)

MeSO4–

(12)

Et2NH

20 °C

CHCl3, 20 °C

X = CO, 46%X = SO2, 24%

Scheme 3

+

"c# From `uanidines and their salts[ Weingarten ð57T1656Ł described the displacement of a singledimethylamino group from the tetramine "04# by heating it with phenylacetylene[ In the early 0889s\Kantlehner et al[ used the sodium salt of alkyne to achieve a similar reaction with hexa!methylguanidinium chloride] the monoadduct "05# giving rise to a proportion of the interesting 1 ] 0adduct "06# on distillation ð89CZ065Ł[ This latter material could be more conveniently prepared


directly by bubbling alkyne through a mixture of the other reagents[ The reaction of the sameguanidinium salt with phenyllithium gave a reasonable yield of the triamine "07# ð60JOC1774Ł[

Kantlehner et al[ have also published a route to triaminomethanes "08# by mixed hydride reductionof guanidinium salts ð72S894Ł^ in this case the yield steadily declines with the increasing size ofsubstituents on nitrogen\ perhaps re~ecting the stability of the products[

The alkyltitanium complex "19# has been found to insert into tetramethylguanidine "10# to givethe cyclic triamine complex "11# in very high yield "Scheme 3# ð77BCJ060Ł[

Ph Ph

NMe2

NMe2

NMe2

Ph

NMe2

NMe2

NMe2NMe2

Me2N NMe2

NMe2

NMe2

NMe2

Me2N

Me2N NMe2

NMe2

Me2N NMe2

NR2

R2N NR2 NR2

R2N NR2

+

Cp2Ti

Ph

Ph

heat

88%(15)

C(NMe2)4

+

NH

Me2N NMe2

+

, THF

Cl–

Cl–

HN

Cp2TiPh

Ph

∆, distil20%

PhLi, Et2O

52%

NaH, (16)

NMe2Me2N

76%

(17)

NaH2[Al(OCH2CH2OMe)2]

33–55 %(19)

+

CNaHC

92%

(22)

Scheme 4

CHHC

57%

(18)

(20) (21)

"d# From ortho!acid derivatives[ The _rst reported synthesis of this type came from Bredereck etal[ who prepared triformamidomethane "03# by treating triethyl ortho!formate with formamide inthe presence of an acid catalyst "Scheme 4# ð48CB218Ł[ Follow!up studies were made in which thenature of the amide was varied and\ by controlling the stoichiometry of the reaction together withthe use of toluene as solvent\ the yields were signi_cantly improved ð59CB0287\ 52CB0494Ł[ The formylgroups in "03# could be exchanged for other acyl derivatives to give "12# by reaction with anappropriate acid anhydride ð59CB0287Ł[ Urethane has been used in this context with high yields ofthe tricarbamate "13# reported ð56ZOR0638Ł[

Triethyl ortho!formate will also react with N!methylaniline to give the product "4# "Scheme 5# inmoderate yield ð51JOC2553Ł[ Triethoxyacetonitrile "14# reacts with pyrrolidine among other aminesto give the unusual nitrile "15# ð68GEP1713917Ł[

Heating diaminoalkoxymethanes of type "16# gives rise to disproportionation to amide acetals"17# and triaminomethanes "08# "Scheme 6# ð57CB40Ł[ Dithioacetals such as "29# react with suc!cinimide "18# to give the substitution products "20# ð54IZV1068Ł^ phthalimide behaves similarly[

Weisman et al[ synthesised the interesting tricyclic examples "23# by reaction of formamide oracetamide acetal "21# with macrocyclic triamines "22# ð70TL3254Ł[ They found that acetals such as"21# were preferable to simple ortho!esters[ Triazaadamantane "25# was made by condensation oftriethyl orthoformate with cyclohexanetriamine "24# "Scheme 7# ð62CB1412Ł[

"e# From alkyl halides[ Clemens et al[ prepared triamines "4# by treating the sodium salts of N!alkylanilines with trihalomethanes ð51JOC2553Ł^ for this conversion di~uorochloromethane wasbetter than either chloroform or dichloro~uoromethane[ This reaction may well proceed through acarbene intermediate and in support of this the pyrolysis of sodium trichloroacetate in the presenceof such anilines gave "4# in modest yields "Scheme 8#[ Similar chemistry has been successful using a


OEt

EtO OEt

HN O

HNHN

O

O

(14)

NH O

HNHN

O

(23)

R

R

R

O

NH O

HNHN

O

(24)

OEt

OEt

OEt

O

(RCO)2O, ∆HCONH2, H+

32%

H2NCO2Et

90%

Scheme 5

OEt

EtO OEt

N

N NMe Me

PhPh

Me Ph

N

OEt

OEt

OEtNH

+Et2O, ∆

57% N

N

NN

(5)

PhNHMe, ∆

57%

(26)

(25)

Scheme 6

+

(19)(27) (28)

Scheme 7

OR

R2N NR2

OR

R2N OR

NR2

R2N NR22

NH

+50%

(31)

(30)

O OSEt

SEtMe2N

(29)

N

Me2N N

O OO

O

pyrazole as the amine component ð65S687\ 68LA0345Ł although 0\1\3!triazoles ð58JCS"C#1140Ł andindazoles ð68LA0345Ł gave very poor yields[

"f# From titanium salts[ Tetrakis"dimethylamino#titanium "26# reacts with DMF in ether to givea high yield of triaminomethane "27#\ whereas the corresponding acetamide derivative gave thediaminoethylene "28# ð55JA749\ 55JOC1763Ł[ Similarly\ oxamide "39# gave the same product "27#although no yield was reported "Scheme 09# ð57JOC0135Ł[

"`# Addition to polyaminoethenes[ Tetraaminoethenes "30# react with lactams and imides to givethe cyclic triamines "31# ð64CB104Ł^ this type of reaction is covered in a review of similar chemistryð61AG"E#853Ł[ Exomethylene triazinediones "32# have been shown to combine with some substituted


HC(OEt)3, ∆

27–31%

(36)(35)

NHRNHR

NHR NN

NRR

R

Scheme 8

N

NH HN

(CH2)n

(CH2)p

(CH2)m N

N N

(CH2)n

(CH2)p

(CH2)m

R

H

+NMe2

MeO OMeR

43–89%

(33)(32) (34)

H

NAr Me

CHClF2, NaH

Ar = Ph58%

N

N N

Me Ar

Me

Ar

Me

Ar

Cl3CCO2Na, ∆

20% (5)

Scheme 9

Ti(NMe2)4NMe2

Me2N NMe2

(37)

(Me2NCO)2 (40)

Me2NH

Ti(NMe2)4 + MeCONMe2

(37)87%

NMe2

NMe2

(38)HCONMe2

Et2O83%

(39)

Scheme 10

hydrazines by reaction at the ring carbon giving products such as Structure "33# "Scheme 00#ð64CR"C#452Ł[

N

N N

N

Ph Ph

PhPh

NN

N

Ph

Ph O

HN

O

H2NNMe2N

N

NRR

R

O O

N

N

NRR

R

O O

(CH2)n+

(41)

toluene, ∆

67–91%

N NMe2

H

(42)

(CH2)n

(43) (44)

Scheme 11

"h# Heterocyclisation reactions[ In an attempt to prepare an oxazoline "35# by pyrolysis ofhydroxyethylamide "34#\ Slusarczuk and Joullie� obtained the tricyclic compound "36# in modestyield ð69CC358Ł[ The bis"amide# "37# is reported to extrude one molecule of benzimidazole on


sublimation giving triamine "38# ð66JCS"P0#0051Ł\ and in a similar transformation\ the acylation ofdiamide "49# with chloroacetyl chloride gave the tetracycle "40# in high yield "Scheme 01# ð70JOC0460Ł[

F3C NH

OH

O O

N

N

N

N

F3 C

CF3

HN

N O NO

N N

HN

H2N O NH2O

N N

N

O

O

N

NH

NH

O

O

Cl

∆

30%

(47)

(46)

(48) (49)

(50) (51)

∆, sublime

92%

83%

ClCl

O

(45)

Scheme 12

"i# Radical methods[ The dimerisation of triarylimidazoles by treatment with potassium fer!ricyanide under appropriate conditions gave the photochromic dimers "41# among other products"Scheme 02# ð55JA2714\ 60JOC1151Ł[ Treatment of acetonitrile with the N!bromosuccinimide complex"42# gave the trisubstituted acetonitrile "43# ð77ACS"B#555Ł^ other aminoacetonitrile derivatives "44#and "45# gave better yields of similar products[

"j# From other triamines[ As part of a wider study\ Katritzky et al[ have trapped the anion oftris"benzotriazolyl#methane "46# with a variety of electrophiles such as alkyl halides and alkylchloroformates "Scheme 03# ð89S555Ł[

"k# From isocyanates[ Working independently\ two research groups have found that DMF reactswith phenyl isocyanate to give the bicyclic triamine "47# ð57JOC2817\ 57JOC2820Ł[ According to thelatter report this product was also obtained from amidine "48#[ Since then a number of similarreactions have been described] among other similar substrates\ lactams ð62JOC1503Ł\ amidinesð57CB2991\ 58CB820Ł\ amidinium salts ð60LA"640#034\ 79HCA0847\ 71CB0610Ł\ tetraaminoethylenesð60LA"637#0\ 63CB0820Ł and 0\0!diaminoethylenes ð66CR"C#210Ł have all been utilised in place of DMF"Scheme 04#[ Thiocyanates also reacted similarly ð64CB0031Ł[ The cyclic selenourea "59# has beenused as a source of the carbene "50# "which can also be formulated as an amidinium ylide# ð72CB1957Ł^this reacts with phenyl isocyanate to a}ord the product "51#[ Reduction of isocyanates in situ hasbeen used to provide the source of the spiro carbon atom in "52# ð74CB2848Ł[

5[94[0[0[1 0\0\0!Trinitroalkanes

"i# Introduction

Much work has been done in this area of chemistry but the special advantages o}ered by thesematerials in the _eld of propellants and explosives represent a signi_cant hazard in the hands of the


N

O

O

NO O

N

O

O

CN

N–O ONO O

Br

N

HNAr

Ar

Ar

N

NAr

Ar

Ar

N

NAr

Ar

Ar

N

O

O

CN

(54)

Bu4N+

N

O

O

CN

(53)

K3Fe(CN)6

43–95%

MeCN

22%

(52)

(55) (56)

Scheme 13

i, BuLi, THF; ii, EX

E = PhCH2, CO2Et, Bun inter alia

Scheme 14

NN

N

NN

N

NN N

(57)

NN

N

NN

N

NN NE

i, ii

58–98%

unwary[ Several reviews have been published\ the most recent being in the Patai series ðB!69MI 594!91Ł^ others cover more general aspects of nitroalkane chemistry as well as their synthesis ð48UK373\52T"S#044\ 52T"S#066\ 53CRV08\ 55UK0639Ł[

The presence of three strongly electron!withdrawing nitro groups attached to a single carbonatom has a profound in~uence on the chemistry of such compounds and even though not all thenitro groups are coplanar\ they are still prone to elimination and substitution reactions as well asrendering b!heteroatoms virtually non!basic[

"ii# Preparation

There are two fundamental approaches to the synthesis of such compounds] the introduction ofan intact trinitromethyl group "most commonly as a nucleophile but also as a radical# and thestepwise introduction of the required nitro groups[

"a# Addition of an intact trinitromethyl `roup[ The trinitromethyl anion adds readily to Michaelacceptors as shown in Equation "0#[ Such reactions are typically carried out in protic solvents andin the absence of added base which can give rise to complicating by!products[ Kaplan and Kamletreport that for addition to acrylates the optimum pH is around 2[4 ð51JOC679Ł[ Addition occurs tounsaturated ketones ð57JOC0136Ł\ aldehydes ð57JCED326Ł\ phosphonates ð67MI 594!90Ł\ oximes


N

N

N

N

N

Ph

O O

O Ph

OPhPh Ph

NMe Me

N

Ph

N

N

Ph

Se

PhN

N

Ph

PhN

N+

Ph

Ph

N

N

N

N

Ph

Ph

O

PhO

Ph

N

N

N

N

N

R

O O

O R

ORR

:

(61)

(59)(58)

140–150 °C

96%

HCONMe2 + PhCNO

R

–

(63)

PhNCO

47%

(60) (62)

53%

RNCO[HRu3(CO)10(SiEt2)]N(PPh3)2, Et3SiH

22–69%

Scheme 15

ð79MI 594!91Ł\ lactones ð75JHC70Ł and to acrylonitrile ð60ZOR29Ł[ However\ according to Kaplan\addition to symmetrically disubstituted Michael acceptors does not occur ðB!69MI 594!91Ł[

NO2

O2N NO2

EWGEWGO2N

NO2O2N+ (1)

EWG = CO2R, CHO, COR, PO(OR)2, CHNOH, CN

A detailed study of the alkylation of the silver salt of trinitromethane has been made ð52T"S#066Ł\and although this method worked well for simple alkyl\ allyl and benzyl groups it failed for otherelectrophiles such as haloacetates[ One particular complication is the occurrence of competing O!alkylation ð57IZV336\ 66IZV025Ł[ Nevertheless\ variations on this method\ including the use of othersalts\ have allowed reactions to occur with diiodomethane ð60ZOR0293Ł\ 0!bromoadamantaneð65KFZ24Ł\ a!chloroamines ð70IZV1035Ł\ ferrocene derivatives ð75ZOR0282Ł\ triazolyl diazonium saltsð61KGS602Ł and a!chloroethers ð89SC2292Ł as illustrated in Scheme 05[ At the beginning of the 0889s\a study of the phase transfer catalysed methylation of the potassium salt of trinitromethane waspublished ð89IZV0705Ł in which the addition of a crown ether or polythylene glycols was shown tobe advantageous[ This salt has also been used to substitute the pyridinium salt "53# in modest yieldsð72IZV1544\ 89TL6268Ł[

Iodotrinitromethane and tetranitromethane are methylated in dipolar aprotic solvents "seeScheme 06# either via intermediate solvent alkylated species or perhaps through preliminary homo!lytic dissociation ð69ZOR078\ 63ZOR1992Ł[

Trinitromethane is methylated by diazomethane ð69IZV837Ł[ Diazo compounds such as "54# insertinto bromo! or iodotrinitromethane to give trinitro derivatives "55# ð60ZOR0015\ 66ZOR0448Ł[ Tri!and tetranitromethane react with other nitroalkanes to give trinitromethyl derivatives such as "56#ð62IZV011Ł and "57# ð56USP2205200Ł\ and\ in the presence of a silylating agent\ with "58# to give ethersof "69# "Scheme 07# ð78MI 594!90Ł[

Shechter and Cates\ Jr[ found that trinitromethane reacted with enol ethers "60# at the oxygen!bearing carbon to give "61# ð50JOC40Ł^ this reaction is also reported for enol acetates in alcoholicsolvents giving products of type "62# "Scheme 08# ð58IZV1455Ł[

Trinitromethane reacts with formaldehyde to give alcohol "63# ð49JA4218\ 59JOC1958Ł[ In the


N N N

F

O2N NO2

NO2

NO2

NO2NO2

NN

NH

RNO2

NO2

NO2

O2N NO2

NO2

RN

O2N

RNO2O2N

ORO2N

NO2O2N

IO2N

NO2O2N

NO2O2N

NO2

R2N Cl

X–+

RO I

KC(NO2)3

(64)

AgO2N

NO2O2N

7%21%

Scheme 16

41%7%

H2OMeCN

RO2N

NO2O2N

RBr, AgObenzene

44%53–75%

Et3N

O2N

NO2

35%

Ag, salt, CH2I2Et2O

NOR

O–

CH2Cl2/DMF

HetN2+14–61%

++RX

CO2EtN2Br

NO2

NO2NO2

CO2Et

BrNO2

NO2

dioxan

51%

X = NO2, 64%X = I, 90%

67%

NO2

NO2

NO2

X

NO2

NO2

NO2

O2NNO2

NO2

DMSO or DMFMeI

CH2N2

Scheme 17

(65) (66)


O

O

NO2

NO2

O2N+OH

OO2N

NO2O2N

(67)

water, ∆

32%

TMS-I,

–78 °C

65%

ClCl

(68)

, base

(69)

O2NNO2

NO2

NO2

NO2NO2

NO2

NO2

ONO2

NO2

ONO2

NO2NO2

O2NNO2

NO2

(70)

Scheme 18

R NO2

NO2NO2

OR

NO2

NO2NO2

OR

ROR

OAc

O2NNO2

NO2

O2NNO2

NO2

ROH, ∆

28–76%

dioxan

50–81%

(71) (72)

(73)

Scheme 19

presence of amines such as "64# ð51JOC0344Ł and using hydroxymethylamides "65# ð50JOC280Ł\ theMannich reaction occurs[ In the mid 0879s\ silylaminal "66# has been shown to react with silylatedtrinitromethane "67# under non!aqueous conditions to give amine "68# ð74IZV1524Ł[ Similar additionsto higher aldehydes and ketones are reversible "Scheme 19# ð59JOC1958Ł[ Trinitromethane has alsobeen reported to add to preformed imines such as "79# and "70#\ in these cases in halocarbon solventsð57IZV1268\ 58IZV1298Ł[

Polynitromethanes have been added to various substrates via a radical mechanism to providetrinitromethane derivatives[ Tetranitromethane is reported to form charge transfer complexes withelectron!rich aromatics such as anthracene^ subsequent photolysis can give rise to trinitroarenes"71# "Equation "1## ð74JOC4134Ł[ Other aromatic systems can lead to products such as "72# ð75RTC167Łand "73# ð79MI 594!90Ł[ Products such as those of direct nitration may also be formed and the exactcourse of the reaction can be di.cult to predict ð75RTC167Ł[

XX NO2

O2N NO2

NO2

C(NO2)4hν >500 nm, CH2Cl2

16–93%(2)

(82)

Tetranitromethane will add across alkenes such as "74# ð58ZOR1135Ł and "75# ð75RTC175Ł and in


NO2

O2N NO2

O2NOH

NO2O2N

HONH2

HO

HN

NO2

O2NNO2

HN

O

OHHN

O

NO2

O2NNO2

N

R

RO-TMS N

–O O-TMS

O2N NO2

NNO2

O2NNO2

R

R

NO2

O2N

HN

N

NO2

O2N

HN

NH

CH2O

NO2

O2NNO2

(74)

HC(NO2)3, H2O

87%

HC(NO2)3, aq. CH2O

34%

NO2 NO2

(75)

(76)

+

+

N

(77)

NH

(78)

O2N NO2

NO2

HC(NO2)3, CHCl3

76%

(80)

(79)

(81)

HC(NO2)3, CCl4

73%

Scheme 20

OMe

NO2

NO2NO2

(83)

NO2

NO2NO2

(84)

such cases light is not always required "Scheme 10#[ Insertion into a C0H bond of THF a}orded"56# ð62IZV0038Ł^ a similar reaction occured with iodotrinitromethane "Scheme 11# ð61IZV389Ł[

MeO MeO

NO2

O2N

NO2

NO2

NN

O2N

NO2O2N

(85)

C(NO2)4

80%

C(NO2)4

40%

(86)

Scheme 21

NO2


O O ORX

NO2

NO2

NO2O

NO2

NO2

NO2+ +

C(NO2)4

35%

THF, ∆X = H, NO2, I

30–50%

(67)

Scheme 22

Electrolysis of salts of trinitromethane as shown in Scheme 12 leads to radicals which react withcyclic ethers ð61IZV1592Ł or with toluene ð61IZV0606Ł and other aromatic systems ð71IZV1526Ł[

NO2

NO2

NO2–

(67)

M+

NO2

NO2NO2

NO2

NO2NO2

R O

NO2

NO2

NO2

e–, toluene e–, PhR

3–25%

e–, THF

Scheme 23

The mercury salt "76# has been shown to add across the double bonds of allyl alcohol ð51IZV161Ł\methyl acrylate ð58IZV0734Ł and vinyltrimethylsilane "Scheme 13# ð62RZC0132Ł[

TMS

CO2Me

OHHg

R

R

NO2

NO2NO2

O2N NO2NO2

Hg(C(NO2)3)2 (87)

Scheme 24

Trinitroacetonitrile undergoes cycloaddition reactions with TMS azide\ diazo compounds andnitrile oxides to give trinitromethyl!substituted tetrazoles "77# ð70JHC0366Ł\ 0\1\2!triazoles "78#ð76ZOR1513\ 77ZOR533Ł and 0\1\3!oxadiazoles "89# ð75ZOR1507Ł respectively[

N

NNH

N

NO2

O2N

O2NN

NN

NO2

O2N

O2N

N

NO

Ar

R

R

NO2

NO2

NO2

(88) (89) (90)

There have been many reports of the cycloaddition of trinitromethane derivatives with alkenes"Equation "2## to give products of type "80#[ Tetranitromethane has been shown to react directlywith cyclohexene ð56ACS"C#0281Ł\ ethylene ð55ZOR0891Ł\ vinyl ethers ð58ZOR119Ł and butadieneð58ZOR0202Ł[ Bromo! and iodotrinitromethane have taken part in similar reactions ð56ZOB0052\57IZV510\ 62ZOR158Ł[ Trinitromethane can be O!silylated ð62ZOR785Ł and the resulting adduct reactswith styrene to a}ord "81#[ O!methylation with diazomethane followed by reaction with butadieneyields "82# "Scheme 14# ð57ZOR120Ł[


R

R

XC(NO2)3

X = Br, I, NO2

NO

R

O

NO2O2N

R

R

R

X

(3)

(91)

NO2

O2N NO2

N+

O2N NO2

TMS-O O–O

N

NO2

O2N

O-TMSPh

N+

O2N NO2

MeO O–O

N

NO2

O2N

OMe

(92)

(93)

styrene

94%

butadiene

70%

TMS-Cl

CH2N2

Scheme 25

"b# Successive nitration reactions[ The trinitromethyl group has been assembled by successivenitration from various starting materials[ For example\ trinitromethane itself can be made on acommercial scale by treatment of acetylene with concentrated nitric acid in 63) yield ð52T"S#044Ł[Cyanoacetic acid has been converted to trinitroacetonitrile in good yield using a mixture of nitricacid and sulfur trioxide ð51T68Ł[ Nitrile oxides "83# react with dinitrogen tetroxide to give arylderivatives "84# "Equation "3## ð89IZV0519\ 89IZV0512Ł[ Oximes have been converted to either di!ð77BCJ1816Ł or trinitromethanes ð59IZV0672\ 69KGS489Ł using nitrogen dioxide[

Ar N O–+

Ar

NO2

NO2

NO2

N2O4, CH2Cl2

45–79%

(94) (95)

(4)

Dinitromethanes may be prepared as precursors to their trinitro counterparts^ Kaplan andShechter used silver nitrate:sodium nitrite on the silver nitronates "85# ð50JA2424Ł[ Less conveniently\chloronitromethanes can be nitrated ð53CRV08Ł and tetranitromethane treatment of nitroalkaneshas also been used ð50USP1880204\ 56USP2205200Ł[ Other reagents have been used for the furthernitration of dinitro analogues\ e[g[\ nitryl ~uoride "86# ð60IZV0483Ł[ Tri~uoroacetic anhydride"TFAA# and nitric acid react with dinitroalkenes such as "87# but less successfully with mononitroanalogues such as "88# "Scheme 15# ð81JOC2915Ł[

N

O–

O–

TFAA, CH2Cl290% HNO3

NH

HN NO2

NO2

(98)89%

22%

NH

HN

NO2

+

(99)

NH

HN

AgNO3, NaNO2, NaOHEt2O, 0–5 °C

78%Ag+

NO2

NO2

NO2

MeCH(NO2)2 MeC(NO2)3

FNO2 (97)MeCN

43–67%

Scheme 26

(96)


5[94[0[0[2 Mixed nitro and other functions

One nitro group in trinitroethane has been displaced by azide in DMF as shown in Scheme 16ð73BRP1012718Ł[ The same product was obtained by electrolysis of the sodium salt of dinitroethanein dilute sodium azide ð64USP2772266Ł and other examples have been similarly prepared ð89MI 594!90Ł[

NO2

NO2

NO2

NO2

NO2

NaN3, DMF

28%

aq. NaN3, e–NO2

NO2

N3

Scheme 27

5[94[0[1 Functions Bearing Three Phosphorus Atoms

5[94[0[1[0 Introduction

Functional groups of this type fall into two main classes] those with tri! or pentavalent phosphoruswhich are predominantly used as ligands in organometallic chemistry "e[g[\ ð81OM15Ł#\ and tris"phosphonato#methanes which have been used as surfactants "e[g[\ ð66USP3919980Ł#[

5[94[0[1[1 Functions bearing tri! or pentavalent phosphorus

"i# From functions bearin` two phosphorus `roups

The method _rst reported by Issleib and Abicht for the reaction of methylenebisphosphines witha chlorophosphine has been subsequently much utilised to prepare ligands for organometalliccomplexes "Scheme 17# ð69JPR345Ł[ The original workers described the reaction of lithium saltsof bisphosphine "099# and its corresponding bisphosphine oxide "090# with diphenylphosphinylchloride to form tris"phosphino#methanes in good yields[ Karsch et al[ extended the work to includealkyl substituents\ preparing methylphosphines "091# ð68AG"E#373\ 68ZN"B#0060Ł[ Grim and Waltonreport phosphine sul_des "092# made by the same basic method ð79PS"8#012Ł^ the paper contains noexperimental details even though a report from the same group mentions the preparation ofasymmetric tris"phosphino#methane "093# ð75IC1588Ł[ In this case\ the reaction was carried out ontransition metal carbonyl complexes of the carbanion of bis"phosphino#methane "094# to improvethe chemoselectivity ð71CC175Ł[

"ii# By further reaction of tris"phosphino#methanes

Tris"phosphino#methanes have been modi_ed at phosphorus to produce a number of oxides\sul_des and selenides in various combinations[ The _rst report was by Issleib and Abichtð69JPR"201#345Ł who converted tris"diphenylphosphino#methane "095# into its trisul_de "096# byheating with sulfur[ This method ð71CB707Ł failed to produce the alkyl analogue "097# which could\however\ be prepared from a bis"thiophosphinoyl#methane by the standard method "Scheme 18#[

Grim et al[ report the modi_cation of a variety of tris"phosphino#methanes] the mild oxidationof phosphine "095# to phosphine oxide "098# avoids the cleavage of one of the carbonÐphosphorusbonds which occurs under harsher conditions ð75IC1588Ł[ This method was then applied to a numberof phosphine sul_des and selenides[ Red selenium was also used to convert phosphine sul_de "009#into "000# although an earlier paper mentions that carbonÐphosphorus bond cleavage occurred insimilar reactions ð79PS"8#012Ł[ Grim also reports that salts of phosphines react more readily withselenium because of a reduction in steric crowding ð76PS"27#68Ł[ The functionalisation of phosphorusin metal carbonyl complexes by oxidation using either hydrogen peroxide or sulfur has been claimedalthough no details are given ð71CC175Ł[ The phosphine imine "001# was prepared in excellent yieldby reaction of phosphine "009# with p!tolyl azide "Scheme 29# ð80CC868Ł[

Karsch et al[ describe the methylation of the lithium salt of tris"dimethylphosphino#methane


PPh2

PPh2Ph2P

Li

PPh2Ph2PPPh2Ph2P

PPh2Ph2P

i, BuLiii, Ph2PCl

O O

PPh2Ph2P

O O

PPh2

Scheme 28

(104)

Ph2PCl

R1, R2, R3 = Ph, Me

PR32

PR22R1

2P

(103)

PR22R1

2P

73%

(101)

i, BuLiii, Ph2PCl

i, Ph2PSCH2Liii, Ph2PCl

(102)

i, BuLi

ii, R32PCl

Ph2P Li

S

– M = Cr, W, Mo

(105)

Ph2P PPh2

S

(100)

Ph2PCl

61%

Ph2P PPh2

S

PPh2

BuLi

86%

Ph2P PPh2

O S

Ph2P PPh2

O S

PPh2

PPh2

PPh2

(CO)4M

Ph2P

Ph2P PPh2

S S

SPPh2

Ph2P PPh2

S8, C6H6

56%

(106) (107)

PMe2

Me2P PMe2

Me2P

Me2P PMe2

S S

S

Me2P PMe2

S S

S8

i, ButLi

ii, Me2PSCl

(108)

41%

Scheme 29

"002#] using low temperatures and ether solvents alkylation occurs at carbon to give "003# whereasin pentane with TMEDA alkylation takes place on phosphorus to a}ord the ylide "004# "Scheme20# ð73ZN"B#0407Ł[

"iii# From phosphaalkynes

Phosphaalkynes\ their oligomers and derived metal complexes have been used to prepare complexpolycyclic analogues of tris"phosphino#methanes[ This chemistry has been reviewed ð77AG"E#0373\


Ph2P

Ph2P PPh2

O O

OPPh2

Ph2P PPh2

Se, ∆

PPh2

Ph2P PPh2

S SPh2P PPh2

S S

(106) (109)

(110)

Scheme 30

TolN3, ∆

>95%

Ph2PNTol

Ph2P PPh2

S S

H2O2, acetone, 0 °C

81%

Ph2PSe

(111) (112)

Me3P

PMe2

PMe2

Li

PMe2

PMe2

PMe2

PMe2

–

(115)(113)

PMe2

(114)

PMe2+MeI, TMEDA, pentane

80%

MeI, Et2O, THF

–115 °C to 20 °C65%

Scheme 31

89CRV080Ł[ Wettling et al[ report that the prolonged pyrolysis of "005# gave the tetraphosphacubanederivative "006#\ albeit in very low yield ð78AG"E#0902Ł[ Prior reaction of the alkyne to form azirconium complex "007# greatly improves the conversion ð81AG"E#647Ł[ The phosphacubane "006#has been functionalised at a single phosphorus vertex using a number of reagents ð81AG"E#768\82JOC3094Ł[ The zirconium complex "007# has been treated with phosphorus trichloride to form thebicyclic compound "008# "Scheme 21# ð80AG"E#196Ł[

But

PP

PP

But

But

But

PBut

PCp2Zr P

But

But

P

PBut

But

PP P

But

Cl

Scheme 32

130 °C, 65 h

8%

(116) (117)

(118)

Cp2ZrCl2BuLi 70% 70%

CCl3CCl3, C6H6

But

PCl3, hexane110 °C

75%

(119)


Aluminum chloride catalysed tetramerisation of the phosphaalkyne "005# yielded polycyclicderivatives such as "019# ð81AG"E#0944Ł[ Tungsten ð80CC0294Ł\ manganese ð82AG"E#0313Ł\ ironð78AG818Ł and vanadium complexes ð76AG"E#897Ł have been converted to related polycyclic systems\for example "010# "Scheme 22#[

(120)

P(CO)5W

NR2

P

P

(CO)5W NR2

P

PP

P

R2N NR2

But

W(CO)5

(116)

i, AlCl3, CH2Cl2, 0–25 °Cii,

But

95%

But

(121)

30%

Scheme 33

PButPBut

P

P

PP

But

But

But

But

Phosphaalkyne "005# reacts with phosphorus ð77AG"E#278Ł and arsenic ð77AG"E#698Ł heterocycles"011#[ In the former case a 1 ] 0 cycloaddition product is obtained whereas in the latter the reactionleads to a 2 ] 0 cycloaddition product minus the elements of benzonitrile "Scheme 23#[

X

N

Ph

Ph PhP

P

AsP

Ph

PhBut

But

But

N

P

P

P

But

Ph Ph

But

Ph

PBut

(122)

X = P

15%

PBut

70%

X = As

Scheme 34

"iv# From phosphorus analo`ues of cyclopentadiene

Di! and triphosphacyclopentadiene anions oligomerise under the in~uence of transition metalsto give complex polycyclic products such as "012# "Equation "4## ð78CC0935\ 81JOM"322#C00\ 82CC200Ł[

P P

P

–PP

–But But

But But

But

+

Li+Li+

P

P

P

P P

But

But

But

But

But

FeCl3 or CoBr2

24%

(123)

(5)

5[94[0[1[2 Functions bearing heptavalent phosphorus

The _rst report of this type of function utilised the reaction of triethyl phosphite with benzoylperoxide in chloroform to form the tris"phosphonate# "013# ð52JCS0416Ł^ the same product wasobtained from the benzoylphosphonate "014#[ The authors report that neither carbon tetrachloride


nor diethyl ether were satisfactory solvents for this reaction[ Several patents claiming similarcompounds as detergents appeared subsequent to this report ð58USP2360395\ 64USP2781565\66USP3919980\ 73USP3339535Ł[ More recently\ generation of the quinonoid "015# and subsequentreaction with diethyl phosphite in the presence of a base has been used to prepare the tris"phos!phonate# "016# in good yield "Scheme 24# ð89PS"36#6Ł[ Gross et al[ have developed this basic methodfurther to produce compounds bearing di}erently substituted phosphorus functions\ e[g[\ "017#ð80PS"51#24Ł[

But

HO

But

PO(OEt)2

PO(OEt)2

But

But

PO(OEt)2

PO(OEt)2

O

But

HO

But

PO(OEt)2

PO(OEt)2

PO(OEt)2

P(OEt)3

(PhCO2)2, CHCl3, 48 h

40%

P(OEt)3, CHCl3

32%

But

HO

But

POPh2

PO(OEt)2

PbO2

80%

HPO(OEt)2NaOEt

71%

(126)

PO(OEt)2

(127)

(128)

Scheme 35

O

Ph P(OEt)2(EtO)OP PO(OEt)

Ph

PO(OEt)

(124) (125)O

5[94[0[2 Functions Bearing Three Arsenic Atoms

This author could locate only two reports referring to this functional group[ Tris"diphenyl!arsino#methane "029# was prepared by reaction of the lithium salt of bis"arsine# "018# with chloro!diphenylarsine ð71OM0003Ł[ The product was used in a study of its complexation properties[ In thesecond report ð82AG"E#092Ł tris"trimethylsilyl#phosphine was desilylated with butyllithium and theresulting lithium salt "020# treated with the arsaalkene "021# in the presence of cobalt"II# chlorideto give tetraarsacubane "022# in moderate yield[ The reaction probably proceeds via an intermediatearsaalkyne "Scheme 25#[

As

AsAs

AsAsBut

But

But

But

But

TMS-As

O-TMS

But

Ph2As AsPh2

Scheme 36

(133)

Ph2As AsPh2

CoCl2

35%

(TMS)2PLi

(131)

AsPh2

(132)

i, BuLi, TMEDAii, Ph2AsCl

60%

(129) (130)


5[94[0[3 Functions Bearing Three Antimony or Bismuth Atoms

This author was unable to locate any references to the functional groups of either of these typesin the literature[

5[94[0[4 Functions Bearing Nitrogen and Other Group 04 Elements

5[94[0[4[0 Functions bearing two nitrogen atoms and one phosphorus atom

Gross and Costisella prepared compound "024# from the amidinium salt "023# by reaction withthe sodium salt of diethyl phosphite ð58JPR814Ł^ Structure "024# was also made by treating uroniumsalts "025# with diethyl phosphite "Scheme 26# ð77ZOB1056Ł[

Me2N OMe Me2N NMe2 OR

Me2N

Me2N

PO(OEt)2

Me2N

Me2N

MeSO4–

+ +

MeSO4–

+

O

X–

Me2NH

O

(EtO)2PNa (EtO)2PH

(134) (135) (136)

R = Me, X = MeSO4–

R = Et, X = BF4–

Scheme 37

The iminium salt "027#\ which was prepared from phosphonate "026# ð60LA"649#33Ł\ reacted readilywith a variety of amines to give the phosphonates "028# or with arylsulfonamides to give "039#[Similarly\ ammonia was added across the imine bond of phosphonates "030# "Scheme 27#ð80PS"52#84Ł[

O

PRO

ROOMe

NMe2

O

PRO

RO

NMe2

O

PEtO

EtONR2

NMe2

O

PEtO

EtONHSO2Ar

NMe2

(137)

Cl–

Cl3C

NCHO

PO(OR)2

(138)

SOCl2

+

Cl3C

NH2

PO(OR)2

(139)

ArSO2NH2

R2NH

39–95%

NHCHO

(140)

NH4OH/CH2Cl2

R = Et, 85%

R = Pri, 73%(141)

Scheme 38

The cyclic orthoamide "031# was treated _rst with diethyl phosphite then with benzylamine toyield the bis"amino#methylphosphonate "032# ð89PS"36#150Ł[ The reaction of the tetraaminoalkene"033# with two equivalents of a dialkyl phosphite gave good yields of the imidazolidines "034# asillustrated in Scheme 28 ð67LA05Ł[

Heating a mixture of pyrazolone "035#\ diethanolamine and phosphite "036# gave the heterocycle"037# ð67MIP76757Ł[ Other cyclic examples "049# were prepared by the cycloaddition of an azide toaminophosphenes "038# but these derivatives were unstable above −59>C ð78NJC780Ł[ The reactionof N!phenylbenzohydrazonoyl chloride to 1\4!dimethyl!0\1\2!diazaphosphole "040# occurs by amultistage cycloaddition process involving two equivalents of the derived nitrile imine and theelimination of benzonitrile to give the bicyclic example "041#\ albeit in low yield "Scheme 39#ð72CB438Ł[


O

ii, Ph NH2

NH

O OEt

O

HN

OH

O

HN

PO(OEt)2

Ph

Scheme 39

O

(RO)2PH, ∆

R = Me, 92%R = Et, 93%R = Bun, 82%

N

N

Ph

Ph

N

N

Ph

Ph

N

N

Ph

Ph

32%

i, (EtO)2PH, ∆

P(OR)2

O

(143)(142)

(144) (145)

NNMe

Ph

NNMe

PhPO(OR)2

N

OH

OHO

O

PRO OR

H

HN

OH

OH

P

NN

N

Ph

Ph

N(Me)R1

R2

PhP

R2

N(Me)R1

NMeN

PNNHPh

Cl

Ph NMeN

P NHPh

NNHPhCl

Ph

(147) (148)(146)

+

NMeN

P

R = CH2CH(Me)Cl

, ∆

+ PhN3

NN

NHPh

Ph Ph

< –60 °C

(149) (150)

+base

Et3N21%

(151) (152)Scheme 40

5[94[0[4[1 Functions bearing two phosphorus atoms and one nitrogen atom

"i# Introduction

This type of functional group has been most widely prepared in the pharmaceutical industry\where such compounds are patented as agents for treating abnormal calcium and phosphatemetabolism such as the bone disorder Paget|s disease\ "e[g[\ ð78EUP187442Ł#[

"ii# Synthesis from ortho!esters and similar derivatives

Gross et al[ have published details of the preparation of aminobis"phosphonato#methanes "042#and the corresponding bis"phosphine# oxides "043# by a method which involves heating ortho!amideseither with dialkyl phosphites or with phosphine oxides "Scheme 30# ð57AG"E#280\ 57AG"E#352\58JPR466Ł[ Thus\ the cyclic ortho!amide "031# was treated _rst with diethyl phosphite and thendiethyl trimethylsilylphosphite to give bis"phosphonato#methane "044# in moderate yieldð89PS"36#150Ł[ The aminopyridine derivative "046# was prepared by the reaction of triethyl ortho!formate with 2!methyl!1!aminopyridine and two equivalents of phosphinite "045# ð70PS"00#200Ł[


Similar chemistry using a mixture of phosphorus species resulted in the analogues "047#ð89PS"40:41#12Ł\ which were also made from the diethoxyphosphinyl acetal "048#[

Me2N

OMe

OMe

Me2N

PO(OR)2

PO(OR)2

O

(RO)2P H, ∆

60–69%

O

R2PH, ∆

55–70%Me2N

POR2

POR2

R = Me, Et(153)

R = Bun, Ph(154)

Scheme 41

NH

O OEt

O

NH

O PO(OEt)2

O

HN

OH

O

PO(OEt)2

PO(OEt)2

HPO(OEt)2

58%

TMS-PO(OEt)2

48%(6)

(142) (155)

N NH2

+ HC(OEt)3 + 2 MeP(OH)OEt150 °C

68%N N

HP

P(7)

(156)

(157)

OMe

OEt

OOEtMe

N NH

P(OEt)2

P

(158)

O

OOH

R (EtO)2PCH(OEt)2

(159)

"iii# Synthesis from amides

Amides have been treated with hydrochloric and phosphorous acids to give variable yieldsof aminobis"phosphonates# "059# ð61ZAAC"278#008Ł^ the reaction of formamides with phosphorustrichloride or tribromide followed by acid hydrolysis resulted in similar compounds ð64BCJ0929Ł[Using a similar procedure\ chloroacetamide "050# was transformed into the corresponding derivative"051# by a mixture of phosphorus trichloride and phosphorous acid ð68ZAAC"346#103Ł and the samemethod was used to prepare "052# ð74LA444Ł[ The unusual phosphorous oxide "P3O5# has also beenapplied to the synthesis of these functions "Scheme 31# ð89PS"40:41#042Ł[ Wet DMF when treatedwith two equivalents of phosphorus trichloride and then more water\ gave the dimethylaminoderivative "053# in good yield\ as shown in Equation "7# ð80PS"45#006Ł[

R2R3N

PO(OH)2

R1

PO(OH)2

ClNH2

O

R1CONR2R3•HClH3PO3

21–77%

ClPO(OH)2

NH2

(160)

PO(OH)2

2 RCONH2 + P4O6 + 4 H2O70–98%

R

NH2

PO(OH)2

PO(OH)2

42%

i, PCl3/H3PO3, dioxanii, H2O, ∆

(162)(161)

Scheme 42


H2N

PO(OH)2

PO(OH)2

(163)

Me2NCHO

i, PCl3ii, H2O

70%Me2N

PO(OH)2

PO(OH)2

(164)

(8)

"iv# Synthesis from nitriles

The earliest report of the preparation of this type of functional group utilised the reaction ofnitriles with phosphorus trihalides and water ð46GEP091244Ł[ This method was subsequently usedby Worms and Blum to prepare aryl derivatives "054# ð68ZAAC"346#198Ł[ In addition\ these workersused the reaction of cyanocyclohexane with phosphorous acid to obtain the cyclohexyl analogue"055#[ This transformation can be carried out in the presence of a ketone] Blum and Hemmanreported that ketone "057# was made from the nitrile "056# and a mixture of phosphorus tribromideand phosphoric acid "Scheme 32# ð77GEP2500411\ 77ZN"B#64Ł[

Ar

PO(OH)2

NH2

PO(OH)2

CN

NH2

PO(OH)2PO(OH)2

H3PO4, PBr3, dioxan

R = t-alkyl38–66%

RCN

O

R

O

PBr3, H2O

Ar = Ph60%

ArCN

NH2

PO(OH)2PO(OH)2

H3PO3

74%

(166)

(165)

(167) (168)

Scheme 43

"v# Synthesis from imidoyl compounds

The reaction of imidate "058# with sodium diethyl phosphite in benzene gave tetraethyl bis"phos!phonato#benzylamine "069# ð48LA"512#092Ł[ In a similar way\ diethyl phosphite was added to imidoyl!phosphonate "060# to give aminobis"phosphonato#methane "061# "Scheme 33# ð60LA"649#33Ł[ Thetreatment of imidoyl halides with phosphorous acid gave rise to the parent acids "062#ð61ZAAC"278#008Ł and similar functions "063# and "064# were obtained using triethyl phosphiteð70PS"00#200\ 71SC304Ł and diethyl phosphinite ð70PS"00#200Ł\ respectively[

"vi# Synthesis from other bisphosphorus species

In attempts to prepare aminotris"phosphonato#methanes "066# by addition of diethylphosphiteto the imine bond in "065# Gross and Costisella actually obtained the product of reduction "067#via an unexpected carbon to nitrogen phosphorus migration "Scheme 34# ð61JPR858Ł[ This methodhas since been used to prepare similar derivatives "068# ð63PS"3#130\ 65JPR161Ł[


Ph

PO(OEt)2

NH2

PO(OEt)2

O

(EtO)2PH

Ph

NH

OEt

O

(EtO)2PH

(EtO)2P NMe2

O

(170)

, Na, benzene

H2N

PO(OEt)2

PO(OEt)2

R1 NR2R3

(169)

(173)

63%

+Cl–

Cl

39%

R1

PO(OH)2

NR2R3

+

(171)

PO(OH)2

Cl–

(172)

H3PO3

15–78%

Scheme 44

R2N

PO(OEt)2

PO(OEt)2

(174)

Me2N

P

P

O

O

OEt

Me

OEt

Me

(175)

Scheme 45

R1HN

PO(OEt)2

PO(OEt)2

PO(OEt)2

O

(EtO)2PH

(177)

R1HN

PO(OEt)2

PO(OEt)2

(178)

R1N

PO(OEt)2

PO(OEt)2

(176)

R1 = Ar, 23–71%

R1HN

POPh2

POPh2

(179)

"vii# Miscellaneous syntheses

The reaction of aryl isocyanides "079# with dialkyl phosphites and base is reported to give theanilines "070# ð64ZOB0349Ł[ Ferric chloride catalysed displacement of chloride from isocyanate "071#by ~uorophosphite yields the unusual isocyanate "072# ð66ZOB210Ł[ Dehydration of the aminoalcohol"073# by heating with hexamethyldisilazane gave rise to a mixture of bis"phosphonato#pyrrolidine"074# and the product of further loss of phosphite "Scheme 35# ð89PS"43#086Ł[ Diphosphacyclobutanes"076# have been obtained by dimerisation of the phosphorous analogues "075# of amidinesð79ZAAC"351#029\ 71ZAAC"374#12\ 72PS"07#16\ 80PS"50#250Ł[


OCN

P

P

OOEt

FOEt

FO

OCN

Cl

Cl

O

R2PH

R1 NC R1 NH

POR2

R2OP

58–75%

(180)

, alkoxide

(181)R = alkoxy, alkyl

FeCl3

30%

(183)

+ 2 (EtO)2PF

(182)

N PO(O-TMS)2NH PO(O-TMS)2

PO(O-TMS)2

NH2

OH

PO(OH)2

PO(OH)2 +(TMS)2NH

(184) (185)

RP

PR

NMe2

Me2N

RP

NMe2

(186) (187)Scheme 46

5[94[0[4[2 Functions bearing nitrogen and other group 04 elements

Kellner et al[ described the reaction of diphenylarsane with tetramethylamidinium chloride inacetonitrile to give bis"dimethylamino#methyldiphenylarsane "077# ð67JOM"038#056Ł[ This reactionproceeds in poorer yield when the sodium salt of the arsane is used in THF[ Imidoyl chloride"089# forms the cyclic derivative "080# by reaction with aminoarsane "078# "Scheme 36# ð67ZC341Ł[Treatment of arsenadiazole "081# with diphenylnitrile imine gives the bicyclic analogue "082#ð75TL1846Ł[

HAsPh2, MeCN

78%

AsPh2

Me2N NMe2

20 °C

70%+

Me2N NMe2

+BuLi, Et2O

Cl–

+

(188)

N

As

NHPh

But

Et

EtNH

NH

As

Et

But

Et

But NPh

ClNH

AsH

Et

Et

(189) (190) (191)

N

N As

Ph NNHPh

Cl AsN

NNN

Ph

MeOC

MeOC Ph

(192) (193)

Scheme 47

The bis"nitro#methylstibane "083# is formed when the silver salt of 0\0!dinitroethane is treatedwith diphenylstibyl chloride\ as shown in Equation "8# ð74IZV328Ł[


MeC(NO2)2Ag + Ph2SbCl Ph2Sb

NO2

NO2

CH2Cl2, <10 °C

90%(194)

(9)

5[94[1 FUNCTIONS CONTAINING GROUP 04 ELEMENTS WITH METALLOIDS

5[94[1[0 Functions Bearing Group 04 Elements and Silicon

5[94[1[0[0 Functions bearing nitrogen and silicon

"i# From silyl halides

This general method involves deprotonation of the carbon atom attached to a nitrogen functionfollowed by silylation[ Thus\ methyl isocyanide has been successively deprotonated and silylated toa}ord bis"trimethylsilyl#methyl isocyanide "084# ð69JOM"14#274Ł\ the second silylation going in muchpoorer yield than the _rst[ The product "084# was converted to the corresponding isothiocyanateusing sulfur ð71BCJ0052Ł[ Katritzky et al[ prepared bis"trimethylsilyl#methylbenzotriazole "085# bythe same method and studied its further alkylation "Scheme 37# ð77RTC530Ł[ More recently\ Snieckusand co!workers showed ð78TL4730Ł that whereas N\N!dimethylbenzamide could be readily silylatedusing lithium tetramethylpiperidide to yield "086#\ the corresponding diethylamide or piperididegave O!silyl products[

TMS NCTMS NC

TMS

NN

N

TMSTMS

NN

N

TMSTMS

R

NN

N

TMS

MeNC

i, BuLi, –78 °Cii, TMS-Cl

80%

i, BuLiii, TMS-Cl

40%

i, BuLiii, RX

NMe

O

TMS

TMS

(195)

(196)

R = Me, 90%R = PhCH2, 95%

(197)

NMe2

O

90%

i, LDA/THF –78 °Cii, TMS-Cl

i, LiTMP, THFii, TMS-Cl

LDA = lithium diisopropylamide

Scheme 48

"ii# By reductive silylation

Amides have been treated with silyl halides in the presence of metals to give bis"tri!methylsilyl#aminomethanes[ Thus\ N\N!dimethylbenzamide\ when added to TMS!Cl and mag!nesium in hexamethylphosphoramide "HMPA#\ gave "087# in modest yield ð60JOM"21#68Ł[ Theauthors report that the reaction fails using N!methylbenzamide[ Ekouya et al[ studied the samereaction using formamides and lithium metal in THF and found the addition of triethylamine to beadvantageous ð68JOM"066#026Ł[ In this case\ the product "088# was formed in only trace amounts inthe absence of base "Scheme 38#[ Picard et al[ made bis"trimethylsilyl#aminomethane "199# in goodyield by treatment of TMS!CN with TMS!Cl and lithium in HMPA ð80JOM"308#C0Ł[

052Group 04 with Metalloid"s#

Ph

NMe2

TMS

TMS

(198)

PhCONMe2

TMS-Cl, Mg, HMPA

32%

N

TMS

TMS

(199)

HCONH2

TMS-Cl, Li, THF, Et3N

30%

TMS

TMS

H2N

TMS

TMS

(200)

i, TMS-Cl, Li, HMPAii, MeOH

65%TMS-CN

Scheme 49

"iii# Miscellaneous methods

Bis"trimethylsilyl#chloromethane has been reported to react with sodium azide in HMPA^ sub!sequent reduction using LAH leads to the amine "199# "Equation "09## "ð80JOM"308#C0\ 81TL2892Ł#[

Cl

TMS

TMS

N3

TMS

TMS

H2N

TMS

TMS

NaN3, HMPA LAH, Et2O

76%

(200)

(10)

Silaneimine "190#\ when treated with dimethylethylamine at elevated temperatures\ inserts intotwo of the C0H bonds of a methyl group of the amine resulting in the formation of the silaneamine"191# "Scheme 49# ð76CB0246Ł[

MeEtN

SiMe2NHSiBut3

SiMe2NHSiBut3

Me2Si

NMe2Et

NSiBut3

NSiBut3Me2Si

NH

TMSMe2Si TMS

HNN

TMSMe2Si TMS

N

(202)

+

NC

–

(201)

EtNMe2

67%

Me2SiTMS

TMSLAH, Et2O

85%

135°C

39%

Pd(OAc)2

56%

(203) (204) (205)

Scheme 50

The aryl isocyanide "192# reacts with octamethyltrisilane in the presence of a palladium catalystto give the bis"silylimine# "193# which when reduced with LAH results in the formation of thecorresponding amine "194# in good yield ð77JA2581Ł[

5[94[1[0[1 Functions bearing phosphorus and silicon

"i# From silyl halides

In a manner exactly analogous to the nitrogen series\ the quenching of a phosphorus stabilisedcarbanion by a silylating agent has been widely used to prepare this functional group[ Phosphine


sul_de "196# was prepared by reaction of the lithium salt "195# with excess TMS!Cl ð63ZAAC"393#193Ł[Phosphines "197# have been further silylated in good yields ð70ZAAC"364#07\ 73CB1952Ł and phos!phonates "198# have been similarly treated "Scheme 40# ð76JOM"212#024Ł[ Trimethylphosphine hasbeen doubly deprotonated using t!butyllithium and successively silylated to give "109# ð77ZN"B#0305Ł[

PhPTMS

SPh

TMS

PhPLi

SPh

PhPTMS

TMS

R

PhPTMS

R

ORPTMS

OOR

TMS

ORPTMS

OOR

TMSORP

OOR

Me

(207)(206)

MePTMS

TMS

i, BuLi, TMEDAii, TMS-Cl

R = alkyl, Ph, 41–65%

(208)

Me

i, LDA, THFii, TMS-Cl

TMS-Cl

65%

MePTMS

91–92%

i, LDAii, MeI

Me

(209)

R = alkyl, 25–85%

PMe3

i, ButLiii, TMS-Cl

i, ButLiii, TMS-Cl

(210)Scheme 51

LDA = lithium diisopropylamide

Bis"phosphino#methanes "100# have been silylated using butyllithium as a base to a}ord bis"phos!phino#trimethylsilylmethanes "101# "Equation "00## ð68CB537\ 77ZN"B#0305Ł[

i, ButLiii, TMS-Cl

TMS

R2P PR2R2P PR2

(211) (212)

(11)

R = Ph, Me

Phosphorus double bonded systems such as "102# and "103# react with nucleophiles at phosphorus"Scheme 41# ð72PS"07#32Ł[ Subsequent silylation in the case of "102# gave "104# whereas protonationat carbon in the case of "103# yielded "105#[

R2NP

TMS

TMS

But2P

TMS

TMS

i, MeLiii, MeOH

P

(214)

P

(216)

TMS

TMS

i, ButLiii, TMS-Cl

(215)

Me

TMS

TMS

(213)

Scheme 52

"ii# From phosphorus halides

Sequential replacement of halogens in phosphorus halides using silyl stabilised carbanions isanother common method for the synthesis of this group[ Phosphorus trichloride when treated with


the lithium salt of bis"trimethylsilyl#methane was converted to either the dichloro compound "106#or its analogous monochloride "107#\ depending on the proportions of the reagents ð79JCS"D#1317Ł[Dialkyl! ð80AG"E#698Ł and diarylchlorophosphines ð72JCS"D#894Ł produce similar products and Grig!nard reagents have also been used with phosphorus trichloride ð89TL2748Ł and aryldichloro!phosphine "108# ð74OM228Ł "Scheme 42#[ Phosphinylidene chloride "119# was converted to theunsaturated derivative "110# in high yield ð71OM0619Ł[

Li

TMS TMS

TMS P

TMS

Cl

Cl

Li

TMS TMS

TMS P

TMS

Cl

TMS

TMS

P

TMS

TMS

2

ClLi

TMS TMS

Et2O, 25 °C

73%+ 1 PCl3

(220)

P

TMS

TMS

(217)

1

+ 1 PCl3

TMS

TMS

(218)

Et2O, ∆

60%

79%

P

(219)

TMS

TMS

ClTHF

PCl2

MgCl

TMS TMS

(221)

+

Scheme 53

The reaction of tris"trimethylsilyl#methyllithium with phosphorus trichloride produced thedichloride "111# ð78JOM"255#28Ł\ which\ after replacement of the halides using sodium methoxide\gave dimethoxyphosphine "112# which readily desilylated in methanol to give bis"trimethylsilyl#!methane "113#[ This desilylation was previously noted in diphenylphosphine "114#\ which althoughstable under basic conditions was much less so at lower pH "Scheme 43# ð72JCS"D#894Ł[

Li

TMS

TMS

TMS P

TMS

TMS

TMS

Cl

Cl

P

TMS

TMS

TMS

OMe

OMe

P

TMS

TMS

OMe

OMe

PPh2

TMS

TMS

TMS

(222) (223)

PCl3, Et2O-THF

65%

(225)

PPh2

TMS

TMS

NaOMe

95%

MeOH

97%

(224)

MeOH, RT

72%

Scheme 54

"iii# Miscellaneous methods

Phosphinylidene derivatives have been reduced under a variety of conditions[ For example\ thephosphine "115# was produced e}ectively by the transfer of hydride from a phosphinyl methyl groupð73ZAAC"400#097Ł[ In another case\ phenylphosphinylidene disilane "116#\ when treated with anequimolar mixture of phenylphosphine and its sodium salt ð76CB0696Ł\ gave the product "117# in


high yield and the chloro analogue "118# has been reduced with concomitant disproportionationusing LAH "Scheme 44# ð76CC0981Ł[

PMe2

TMS

TMSMe2P

TMS

TMS

PMe2

(229)

TMS

TMS

(226)

(228)

Cl

Cl

(227)

toluene, 100 °C

60%

PPh

TMS

TMS

PHPh

TMS

TMSPhPH2, PhPHNa

82%

PCl

TMS

TMS H

PTMS

TMS

TMS

TMS

LAH

Scheme 55

+ TMS-PMe2

The displacement of chloride ion from phosphinylidene chloride "129# with acetylide anions givesrise to the diphosphacyclobutane "120# after dimerisation as a mixture of stereoisomers ð73CB1582Ł[Interestingly\ the aminophosphinylidene compound "121# dimerises with rearrangement to theunusual small ring compound "122# "Scheme 45# ð89CB0134Ł[ Phosphinylidene compounds alsoundergo cycloadditions[ For example\ 1\2!dimethylbutadiene gave the phosphorus heterocycle "123#ð74CB703Ł and diphenyldiazomethane the three!membered epiphosphine "124# ð75CB0866Ł[

TMS M + ClP

TMS

Ph

PPTMS TMS

Ph TMS

TMSPh

P

P

(TMS)2N TMS

N TMS

TMS

TMSTMS-NHP

TMS

TMS

P

Cl TMSTMS

ClP

TMS

TMS

, C6H6, RT

89%

ButP

TMS

TMS

P

TMS

TMSPh

Ph

But

(233)

(230)

(232)

∆

65%

(231)

Ph2CN2

77%

(234)

(235)

Scheme 56

Pentamethylcyclopentadiene groups in the diphosphene "125# have been displaced by the lithium saltof bis"trimethylsilyl#methane to form the newdiphosphene "126# as shown inEquation "01#ð75AG"E#808Ł[

PP

TMS

TMSTMS

TMS

PP

LiTMS

TMS

(236) (237)

(12)


"iv# Modi_cation at phosphorus

There have been a number of reports in which previously formed functions have been modi_edat phosphorus[ Chlorophosphines such as "127# have been reduced using\ for example\ sodiummetal or LAH ð71OM0619\ 74OM228Ł[ Alternatively\ the halogen was replaced by a methyl group"Scheme 46# ð73CC0558Ł[ The phosphine oxide "139# has been produced from its parent compound"128# by a mild oxidation which avoids decomposition ð73JOC4976Ł\ and the reaction of bis"phos!phino#methane "130# with sulfur gives the analogous thio compound "131# ð81CB0222Ł[

Cl

PTMS

TMS

TMS

TMS

H

PTMS

TMS

TMS

TMS

Me

PTMS

TMS

TMS

TMS

O

P

TMS

TMSPh

Ph

(240)(239)

P

TMS

TMSPh

LAH

82%

(241) (242)

Li, MeCl

Ph

S8, toluene, 50 °C

95%

H2O2, acetone, 4 °C

89%

P

S

TMS

P

S

Me Me

MeMeP

TMS

PMe Me

Me Me

(238)

Scheme 57

The bis"trimethylsilyl#methyl group has\ by virtue of its steric bulk\ been used as a stabilisinggroup in the preparation of bisphosphenes "for a review see ð73POL278Ł# e[g[\ the reaction ofdichloride "106# with hindered phosphine "132# in the presence of 0\4!diazabicyclo ð4[3[9Ł undec!4!ene "dbu# gives bisphosphene "133# ð72CC417Ł[ The analogue "126#\ prepared by treating di~uoride"134# with lithiophosphine "135#\ had a half!life of one week at 19>C ð76PS"20#70Ł[ The samestabilising e}ect has been utilised in producing phosphinyl radicals "136# ð79JCS"D#1317Ł which weresubsequently shown to add to 1\2!dimethylbutadiene to give the corresponding bis"phosphines#"137# "Scheme 47# ð73TL2408Ł[

PH2

But But

But

P

But

But

But

P

TMS

TMS

P

TMS

TMS

PF2 +TMS

TMS

PHLi

TMS

TMS

P

TMS

P

TMS

TMS TMS

TMS PP TMS

TMS

TMS

TMS TMS

TMS TMS

(245)

(243)(217) (244)

TMS P

TMS

(246)

TMS

TMS

i, Et2O, pentaneii, dbu

85%

(237)

THF, dbu

78%

•

(247) (248)

Scheme 58

Cl

Cl


5[94[1[0[2 Functions bearing nitrogen\ phosphorus and silicon

The cycloadditions of t!butyl! ð70AG"E#020Ł and trimethylsilyldiazomethane ð72CC0060Ł withphosphinylidenemethylsilane "138# gave the corresponding heterocyclic examples "149# shown inEquation "02#[

PN

TMS

TMS

TMSN

NPN

TMS

TMS

TMS

R

RCHN2, THF

R = But, TMS

(249) (250)

(13)

5[94[1[0[3 Functions bearing arsenic\ antimony or bismuth

"i# From trihalides

The displacement of one or more halides from the appropriate trihalides has proved the methodof choice for the preparation of these functions[ Gynane et al[ ð79JCS"D#1317Ł produced arsenic andantimony derivatives with either one "140# or two bis"trimethylsilyl#methyl groups "141# by thereaction of appropriate trichlorides with the correct proportions of bis"trimethylsilyl#methyllithium[Bismuth derivatives with three such substituents "142# were similarly prepared ð72IC2310Ł andGrignard reagents have also been used for the synthesis of stibanes "143# ð72POL180\ 73IC1471Ł[ Morerecently\ the pyridyl derivatives "144# were produced in a similar way ð80CC0459Ł "Scheme 48#[

Li

TMS

TMS

MCl2TMS

TMS

Li

TMS

TMS

MCl

TMS

TMS

Li

TMS

TMS

Bi

TMS

TMS

(252)

2

MgCl

TMS

TMS

MCl3 + Et2O

M = As, 70% Sb, 60%

SbCl2TMS

TMS

MCl3 + Et2O

M = As, 61% Sb, 65%

(251)

2

NTMS

LiTMS

Et2O, 0 °C

90%BiCl3 + 3

(253)

NTMS

MCl2TMS

3

Et2O, –40 °C

74%

(254)

SbCl3 +

MCl3, Et2O, –80 °C

M = As, 55%Sb, 70%Bi, 44%

(255)

Scheme 59

"ii# By modi_cation of the `roup 04 element

As in the case of the diphosphenes\ bis"trimethylsilyl#methyl groups have been used to stabiliseheteroatomic double bonds[ Diarsenes "147# were prepared ð72JA4495Ł by reaction of aryl arsane


"145# with dichloroarsane "146# "Equation "03##\ whereas mixed functions "148# were made byreacting the corresponding phosphine with arsenic and antimony dichlorides ð72CC770Ł[

AsCl2TMS

TMS+

AsH2

But But

But

THF, dbu

72%As

But

But

ButAs

TMS

TMS

(14)

(256) (257) (258)

(259) M = As, Sb

P

But

But

ButM

TMS

TMS

The chloroarsane "159# was metallated on treatment with lithium[ Subsequent protonation ormethylation produced the arsanes "150# whereas reaction with stannous chloride gave diarsane"151# ð76JOM"219#C16Ł[ Treatment of dichlorostibane "143# with magnesium in THF resulted in theformation of the unusual cyclotetrastibane "152# "Scheme 59# ð81OM034Ł[

AsCl

TMS

TMS

AsE

TMS

TMS

AsTMS

TMS

TMS

TMS

As

SbCl2TMS

TMS

(262)

Sb

Sb Sb

Sb

(254)

i, Liii, electrophile

2

(263)

TMS

TMS TMS

TMS

TMS

TMSTMS

TMS

22

70%

(261)(260)

E = H ex HCl, 90%E = Me ex MeCl, 73%2

i, Liii, SnCl2, Et2O

Mg, THF

Scheme 60

5[94[1[1 Functions Bearing Group 04 Elements and Boron

A search of the literature revealed many references to carborane chemistry and readers arereferred to specialist texts for further information on this complex subject ðB!69MI 594!90\ 71COMC!I300\ 71COMCI!I432\ 81CRV198Ł[

In the sole report of a simple example uncovered by this author\ Io}e et al[\ disclosed the synthesisof "153# by treatment of dinitromethane salts with chlorodiethylborane "Equation "04## ð63MI 594!90Ł[

Et2BCl + (NO2)2CH2 Et2BCH(NO2)2base

(264)(15)

5[94[1[2 Functions Bearing Group 04 Elements and Germanium

Karsch et al[ ð75JOM"201#C0Ł made germanium compounds "154# and analogous lead derivativesby the reaction of the lithium salt of bis"diphenylphosphinyl#methane with germanium"II# chloride"Equation "05##[

(16)(Ph2P)2CHLi Ge[CH(PPh2)2]2

GeCl2, –40 °C

93% (265)


5[94[2 FUNCTIONS CONTAINING GROUP 04 AND METAL ELEMENTS\ ANDPOSSIBLY A METALLOID

Many such compounds have been prepared without isolation or characterisation as precursorsto the functional groups mentioned earlier in this chapter and hence relevant references can befound above[ The subsequent discussion will refer only to those areas previously uncovered or wherethe chemistry is signi_cant enough to be considered separately[ Work has been done in the area oforganometallic cluster compounds but this falls outside the scope of this chapter[

Many alkali metal salts of dinitromethane derivatives have been made ð46JA3697\ 50JOC3623Ł[ Ithas been shown by x!ray di}raction that the rubidium salt of cyanodinitromethane exists in a formin which the metal atom is closely associated with one of the oxygens ð61ACS0763Ł[ It seems highlylikely that alkali metal salts of other systems\ where delocalisation is possible\ will behave similarly[The reaction of dinitromethane with triethylthallium gave a compound of Structure "155# in whichthe metal is reported to coordinate to both carbon and oxygen atoms "Equation "06## ð60IZV0494Ł[

(17)CH2(NO2)2 + TlEt3 Et2TlCH(NO2)2Et2O

95% (266)

The deprotonation of bispyrrole "156# has been achieved using methyllithium and although formalresonance structures are di.cult to write for the lithium salt\ NMR studies indicate extensivedelocalisation of charge ð79HCA0089Ł[ Katritzky et al[ have studied the use of benzotriazole as astabilising group for anionic centres^ among recent publications is one concerning the generationand use of organolithium species "157# ð80JOC1032Ł[

N N

(267)

NN

N

LiN

(268)

Kau}mann and his group have studied the chemistry of the deprotonation of carbon atomsattached to heavy metals and metalloids\ and a review has appeared ð71AG"E#309Ł[ In some casesthe loss of one of the metal substituents is observed[ The preparation of lithium salts of bis"di!phenylstibanyl#methane and bis"diphenylarsanyl#methane and the subsequent deuteration of theproducts "158# has also been described "Equation "07## ð68TL490Ł[

(Ph2M)2CH2 (Ph2M)2CHLi (Ph2M)CHD

(269)

c-Hex2NLi, HMPA D2O

M = Sb, 68%As, 63%

(18)

M =


6.06Functions Containing at LeastOne Metalloid (Si, Ge, or B)and No Halogen, Chalcogenor Group 15 Element; AlsoFunctions Containing ThreeMetalsVADIM D. ROMANENKOInstitute of Organic Chemistry, Kiev, Ukraine

MICHEL SANCHEZUniversite Paul Sabatier, Toulouse, France

and

JEAN-MARC SOTIROPOULOSUniversite de Pau et Pays de l’Adour, Pau, France


5[95[1 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION "AND NO HALOGEN\CHALCOGEN\ OR GROUP 04 ELEMENT# 061

5[95[1[0 Functions Containin` Three Metalloids 0615[95[1[0[0 Functions bearin` three silicons 0615[95[1[0[1 Functions bearin` three borons 0795[95[1[0[2 Functions bearin` three `ermaniums 0745[95[1[0[3 Functions bearin` mixed metalloids 075

5[95[1[1 Functions Containin` Metalloids and Metals 0785[95[1[1[0 Functions bearin` silicon"s# and metals"s# 0785[95[1[1[1 Functions bearin` boron"s# and metal"s# 0875[95[1[1[2 Functions bearin` `ermanium"s# and metal"s# 1915[95[1[1[3 Functions with mixed metalloid"s# and metal"s# 192

5[95[2 FUNCTIONS CONTAINING THREE METALS 193

5[95[2[0 Three Similar Metals 1935[95[2[0[0 Lithium derivatives\ RCLi2 193

060

061 At Least One Metalloid or Metal

5[95[2[0[1 Mercury derivatives\ RC"H`X#2 1955[95[2[0[2 Aluminum derivatives\ RC"AlX1#2 1975[95[2[0[3 Tin and lead derivatives\ RC"MX2#2 "M�Sn or Pb# 197

5[95[2[1 Three Dissimilar Metals 198

5[95[0 INTRODUCTION

This chapter deals with compounds of the general formula RC"EXm#n"MLk#2−n "E�Si\ Ge\ orB^ M�metal^ R�H or organyl^ X�any substituent^ n�9Ð2# having three heteroatoms "E\ M#bonded to the same carbon[ Most of the organoelement species of this type contain classical two!center\ two!electron {{single|| bonds and formally arise through the replacement of hydrogen atomswith the heteroatoms mentioned[ It is the purpose of this chapter to discuss the preparation andsome of the chemical transformations of these compounds[ A discussion of carboranes\ metalclusters\ and other electron!de_cient molecules which cannot be portrayed in the same manner andexhibit quite di}erent reactivities\ is not included[ For the same reason\ p!metal complexes containinga C"EXm#n"MLk#2−n fragment are also ignored[ However\ the organometallic compounds of thetype RC"EXm#nM2−n "M�alkali metal#\ often better described as heteroatom!stabilized carbanions\are considered[

As will become evident\ the methods of preparation of the above functions are wide and varied[Some of these methods are discussed in monographs by Colvin ðB!70MI 595!90Ł\ Weber ðB!72MI 595!90Ł\ Pereyre et al[ ðB!76MI 595!90Ł\ and Negishi ðB!79MI 595!90Ł[ The latter also contains a detaileddiscussion of standard methods of carbonÐmetalloid and carbonÐmetal bond formation[ Houben!Weyl|s Methoden der Orànischen Chemie ð63HOU"02:1b#0\ 64HOU"02:6#0\ 67HOU"02:5#070\ 79HOU"02:4#16\71HOU"02:2a#0Ł and the appropriate reviews in Comprehensive Orànometallic Chemistry ð71COMC!I"1#0\ 71COMC!I"6#154\ 71COMC!I"6#404Ł etc[ and Comprehensive Orànic Chemistry ð68COC"2#576Ł coverparts of the literature up to 0871[ The preparation and properties of some polyborylated compoundsare also discussed in a monograph by Pelter et al[ ðB!77MI 595!90Ł and in a book by Pelter ðB!76MI595!91Ł[ The chemistry of polylithiated aliphatic hydrocarbons has been reviewed by Maercker andTheis ð76TCC"027#0Ł[ Discussion of certain aspects of the topic can also be found in ComprehensiveOrànic Synthesis ð80COS"0#0\ 80COS"0#376Ł and in a number of other references[ ð53AOC"1#146\ B!56MI595!90\ B!74MI 595!90\ B!74MI 595!91\ 75MI 595!90\ 78MI 595!90\ B!78MI 595!91\ B!81MI 595!90Ł[

5[95[1 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION "AND NOHALOGEN\ CHALCOGEN\ OR GROUP 04 ELEMENT#

5[95[1[0 Functions Containing Three Metalloids

5[95[1[0[0 Functions bearing three silicons

Trisilylmethyl groups\ especially tris"trimethylsilyl#methyl\ "TMS#2C\ have been widely recognizedas versatile building blocks in organic synthesis which have proven their synthetic utility in hundredsof reactions ð71JOM"128#82\ B!74MI 595!90\ 80MI 595!90\ 80MI 595!91Ł[ These burgeoning applications arisefrom the unique properties of trisilylmethyl derivatives[ Trialkylsilyl groups "R2Si# can be considered{{bulky protons|| and have been widely used for the synthesis of sterically protected molecules[ Dueto the acidity of the Si2C0H hydrogen "and hence the availability of the corresponding metalderivatives#\ trisilylmethyl groups can be easily attached to a range of metals and metalloids[ Manyof the resulting compounds show enhanced stability compared to the corresponding unsubstitutedmethyl derivatives and thus are easily handled and studied[ Lastly\ due to the steric as well as to theelectronic e}ects trisilylmethyl groups can stabilize an adjacent carbanionic center or an adjacentcarbonÐheteroatom double or triple bond[

The main synthetic pathways to 0\0\0!trisilylalkanes are]"a# {{direct synthesis|| in the gas phase involving insertion of silicon into a carbonÐhalogen bond^"b# reductive silylation of trihalomethanes^"c# reactions of organometallic carbon nucleophiles with chlorosilanes^

062At Least One Metalloid

"d# derivatization and rearrangements of the compounds already containing polysilylated C0

units[A number of other reactions in which an Si2C function is created are known\ but they are more

of academic interest[

"i# Trisilylmethanes and their linear C!or`anyl derivatives\ RC"SiX2#2

Compounds of this type are known with R�H\ alkyl\ aryl\ hetaryl\ acyl\ and with a variety ofsubstituents on silicon[ The parent tris"silyl#methane "0# is formed in very low yield via LAHreduction of the corresponding chloro derivative "1# ð53CB0888\ 75ZN"B#0416Ł[ This precursor isavailable\ along with other trisilylated methanes such as structures "2#Ð"5#\ in the {{direct synthesis||using a copper catalyzed reaction of elemental silicon with chloroform ð47CB11Ł or other halo!hydrocarbons ð74ZC298\ 82ZAAC"508#0383Ł[

SiH3

H3Si SiH3

SiCl3

Cl3Si SiCl3

TMS

TMS TMS(3)(1) (2)

HC(SiHCl2)n(SiCl3)3–n

(4)-(6); n = 1–3

Attempts were made to obtain tris"silyl#methane by the reaction of silylpotassium\ KSiH2\ withhalomethanes ð50JA791\ 56IC0640\ 64JOM"81#052Ł and the pyrolysis of methylchlorosilanesð56AG"E#566Ł\ but the yields were again in the lower region[ More recently\ tris"silyl#methane wasobtained in high yield by a three!step synthesis presented in Scheme 0 ð78CB1004Ł[ An in situGrignard reaction of easily accessible chlorophenylsilane with bromoform and magnesium gavetris"phenylsilyl#methane "6# in ca[ 49) yield[ The _nal conversion of bromo derivative "7# intotris"silyl#methane "0# has been accomplished through reduction with LAH in a two!phase systememploying a phase transfer catalyst[ A similar route is suitable for the preparation of the homologousbis"silyl#methane ð89CB1976Ł and tetrakis"silyl#methane ð89AG"E#190Ł[

Br

Br Br

SiH2Ph

PhH2Si SiH2Ph

(7)

PhSiH2Cl/Mg

THF, reflux45%

HBr

84%

LAH

83%

SiH2Br

BrH2Si SiH2Br

(8)

SiH3

H3Si SiH3

(1)

Scheme 1

Among the methods which can be employed to prepare tris"organosilyl#methanes the moststraightforward one involves the MerkerÐScott procedure using magnesium or lithium reduction ofhalohydrocarbons and halosilanes in a polar solvent ð52JA1132\ 53JOC842\ 54JOM"3#87\ 69JOM"13#536Ł[The reaction is usually performed by the addition of 0\0\0!trichloro! or tribromoalkane to ahaloorganosilane "usually chlorotrimethylsilane# and Mg"Li# in THF[ In principle the synthesisprovides a general route to symmetrically substituted tris"organosilyl#methanes\ but the correctchoice of reagents and conditions is essential if good yields of pure compounds are to be obtained[Experimental details for the preparation of tris"TMS#methane "2# from chloroform\ chloro!trimethylsilane and lithium metal are described in Inor`anic Synthesis "Equation "0## ð89IS128Ł[A related preparation of the compound "Me1PhSi#2CH "69)# has been described starting fromthe corresponding chlorosilane\ bromoform\ and n!butyllithium ð74JCS"P1#618\ 82JOM"351#34Ł[ Thetrichloromethyl groups of a\a\a!trichloroethane ð52JA1132Ł\ 0\0\0!trichlorotoluene ð67CB2462Ł\ anda\a\a\a?a?a?!hexachloro!p!xylene ð56AG"E#831Ł can also be transformed into the tris"TMS#methylgroups[

Cl

Cl Cl

TMS

TMS TMS(3)

TMS-Cl/Li

THF, reflux72%

(1)

The reductive silylation was shown to tolerate an alkyne function[ Thus hexachlorobutyne!1 and


chlorotrimethylsilane react with lithium metal to furnish hexa"TMS#butyne!1 "8# in 47) yield"Equation "1## ð82JOM"351#20Ł[ Remarkably\ this compound\ owing to the steric shielding of thecentral p!system\ resembles trisilylmethanes in reactivity^ its C2C triple bond cannot be hydro!genated at 199>C:49 atm in the presence of a palladiumÐcharcoal catalyst[

TMS-Cl/Li

THF, 20 °C TMS

TMSTMS

TMS

TMSTMS

Cl

ClCl

Cl

ClCl

(9)

(2)

The partially alkylated halosilanes can also be used to obtain trisilylmethanes[ An example is thepreparation of tris"dimethylsilyl#methanes "09# from dimethylchlorosilane and bromoform or a\a\a!tribromotoluene "Scheme 1#[ Bromination of silanes "09# and the subsequent reactions of thebromosilanes "00# with AgBF3\ t!butylamine\ and water illustrate the possible synthetic routes toSi!functionalized trisilylated methanes ð72JOM"141#170\ 82IC1297Ł[

Me2SiHCl/Mg

THF, reflux

R

Br BrBr

R

Me2(H)Si Si(H)Me2Me2(H)Si

Br2

benzene, 5 °C

R

Me2BrSi SiBrMe2

Me2BrSi(10) (11)

R = H, Ph

AgBF4

ButNH2

H2O

(FMe2Si)3CH

(ButNHMe2Si)3CH

(HOMe2Si)3CH

(BrMe2Si)3CH

Scheme 2

A potentially very promising method for the build up of trisilylated C!0 units is the direct reductivesilylation of carboxylic acid derivatives[ However\ whereas a!bis"TMS#alkanols can be readilyobtained from esters using TMS!Cl:Na in THF ðB!70MI 595!90Ł\ attempts to realize the directconversion of esters into trisilylated alkanes has so far had only limited success[ For example\hexakis"TMS#!1!butene "01# could only be synthesized from dimethyl maleate in 0[4) yield "Equa!tion "2## ð82CB1116Ł[

OMe

OMe

O

O

TMS

TMSTMS

TMS

TMS TMS

TMS-Cl/Mg/TiCl4

HMPA

(12)

HMPA = hexamethyl phosphoramide

(3)

For the synthesis of trisilylmethanes with di}erent silyl groups attached to the carbon atom themajor synthetic pathway is a multistep reaction involving the interaction of a suitable Si!func!tionalized organometallic carbon nucleophile with a halosilane[ Scheme 2 illustrates this method!ology ð65JCS"D#1157\ 71CC0212\ 721AAC"386#10\ 74S606Ł[ Other typical examples are given in Schemes 3Ð5 ð75CB0344\ 76AG"E#473\ 81ZN"B#794Ł[

Direct incorporation of a trisilylmethyl group into organic molecules may be achieved via organo!lithium or organomagnesium derivatives[ The organolithium reagents\ "R2Si#2CLi\ are available bymetallation of tris"silyl#methanes with methyllithium in ether:THF ð69JOM"13#418\ 62JOM"44#198\72CC716\ 73JOM"158#106\ 75CC858\ 89IS128Ł\ but can also be generated at low temperatures from thetris"silyl#methyl halides and lithium metal or via the halogenÐmetal interconversion with phenyl!lithium "Table 0# ð75CC0932\ 81JCS"D#0904\ 81OM1827Ł[ Tris"TMS#methylmagnesium bromide is formedin 64Ð89) yields from "TMS#2CBr "in turn obtained by photobromination of neat "TMS#2CH at079Ð089>C# and magnesium metal in diethyl ether ð81OM1827Ł[

Tris"TMS#methyllithium couples normally with methyl iodide to give the 0\0\0!tris"TMS#ethane[Carbonylation leads to the acid "TMS#2CCO1H in 65) yield ð69JOM"13#418Ł[ The Grignard reagent


TMS TMS

TMS

LiMe4Si

TMS

MgClTMS

Cl

TMS Li (TMEDA)

TMS

TMS Li (HMPA)

TMS

TMS Cl

TMS

TMS SiR3

TMS

TMS Li (THF)

TMS

(PMDETA)

i

ii

iiiii

ivv

viivii

vii

vi

Reagents: i, BunLi/PMDETA, hexane, 20 °C; ii, TMS-Cl, hexane/ether; iii, Mg, ether, 20 °C; iv, ButLi/HMPA, THF,

–40 °C, 5 h; v, BunLi/TMEDA, hexane, 25 °C, 12 h; vi, Li, ether, reflux, 24 h; vii, Me2PhSiCl, THF, 20 °C.

(PMDETA = pentamethyldiethylenetriamine)

Scheme 3

Li

TMS TMSSi

H

H

TMS

TMSTMS

TMS

Si Si

TMS

TMS

TMS

TMS

TMS

TMS

TMS

TMS

Si

I

I

TMS

TMSTMS

TMS2

i ii iii

i, SiH2Cl2, ether/pentane, –78 °C, 66%; ii, I2, 100 °C, 24 h, 37%; iii, C10H8Li, THF, –78 °C, 40%

Scheme 4

Br

TMS TMS

Li

TMS TMS

Si(H)But2

TMS TMS

BunLi

ether, –78 °C

But2SiHF

130 °C, 12 h90%

Br2

CCl4, 0 °C95%

SiBrBut2

TMS TMS

SiMeBut2

TMS TMS

i, MeLiii, H2O

THF/ether97%

Scheme 5

NSi

N

TMS

TMS

ClTMS

TMS

But

NSi

N

TMS

TMS

Cl

TMS

NSi

N

TMS

TMS

Cl

TMS

LiButButLi

pentane–78 °C

CF3SO2O-TMS

Scheme 6

a}orded 0\0\0!tris"TMS#!1!phenylethane "63)# when derivatized with benzyl chloride ð81OM1827Ł[Other carbon electrophiles such as nonenolizable aldehydes\ ketones\ acid chlorides\ and epoxidesreact with "TMS#2CLi to give the functionalized silanes "Scheme 6# ð70JCS"P0#858Ł[ However\ themethod is not completely general^ it is limited by the readiness with which "TMS#2CLi abstracts aproton\ if one is available\ rather than attacks a carbon ð63AG"E#72\ 66CB741\ 70JCS"P0#858Ł[


Table 0 Preparation of trisilylmethyllithium species[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐSubstrate Rea`ent Reaction conditions Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ"TMS#2CH MeLi Et1O:THF\ re~ux\ 4 h 89IS128"Me1Ph#2CH MeLi THF\ re~ux\ 5 h 72CC0289"TMS#2CBr Li ether\ 19>C\ 0 h 81OM1827"TMS#2CBr PhLi ether\ 9>C\ 2 h 81OM1827"MeOMe1Si#2CCl BunLi THF\ −67>C 75CC0932\ 81JCS"D#0904"MeOMe1Si#1"TMS#CCl BunLi hexane\ −67>C 81JCS"D#0904"MeOMe1Si#"TMS#1CCl BunLi THF:ether\ −099>C\ 0 h 74JCS"P1#0576\ 80JOM"394#038*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Li

TMS

TMS

TMS

TMS

TMSTMS

OR

TMS

TMSTMS

Ph

TMS

TMSTMS

O

TMS

TMSTMS

OH

TMS

TMS

TMS

TMSTMS

Br

TMS

TMS O-TMS

Ph

COR

TMS

TMSTMS

MeOCH2Cl or MeOCH2CH2OCH2Cl

78–82%

Br

BCl3 or ZnBr2

65%

66%

NBS

74%

PhCOCl

ethylene oxide

90%

PCC

95%

Scheme 7

R = H or OH

The reaction of tris"TMS#methyllithium with O!ethyl thioformate gave the stable aliphatic thio!aldehyde "02#[ This was reduced with sodium borohydride to give the corresponding thiol "03#"Scheme 7# ð76JA168Ł[

Li

TMS

TMS

TMS +S

TMS

TMS TMS

S

OEtTMS

TMS TMS

HSTHF, –78 °C

16%

NaBH4

100%

(13) (14)

Scheme 8

Tris"TMS#methyl!substituted ethene "04# is reported to be obtained by the reaction of 0\1!dilithioðtetrakis"TMS#Łethane with paraformaldehyde[ The formation of the compound implies 0\1!dianionic rearrangement of the silyl group "Equation "3## ð78JA2637Ł[

Li

TMS

TMS

Li

TMS

TMSHCHO

THF73% TMS

TMS

TMS

TMS

(15)

(4)


A quite di}erent route to trisilylated methanes and their derivatives involves the use as substratesof low!coordinate silicon derivatives[ In principle the insertion of unsaturated silicon compoundsof the type "X2Si#1C1SiR1 into a polar elementÐhydrogen bond provides a general approach totris"silyl#methanes[ Since the silaethenes are initially obtained from polysilylated methanes\ thisappears to be a circuitous technique[ However\ it does lead to the speci_c polyfunctional compoundswhich are di.cult to prepare by other reactions ð73JOM"162#030Ł[ Thus alcohols\ phenols\ thiols\hydrogen halides\ and amines add to the silaethenes "05# and "06# to give the insertion products"Equation "4##[ Ionic reagents like PhSLi and "PhO#1P"O#OLi have been employed in these reactionswith equal success ð70CB2407\ 73JOM"162#030Ł[ The 0\0!dimethyl!1\1!bis"TMS#silaethene also insertsinto the a!CH bond of pyridine to yield the trisilylmethane "07# "Scheme 8# ð75JOM"204#8Ł[ For allthese reactions a nucleophilic attack mechanism can be invoked[

SiMe

Me

X

TMS(5)Si

A

Me

H

TMS

X MeAH

(16) X = TMS

(17) X = But2MeSi

AH = H2O, ROH, RSH, R2NH, HHal

SiMe

Me

TMS

TMS

NN

Si Me

Me

TMS

TMS

H

N

Si Me

Me

TMS

TMS

N+

Si Me

Me

TMS

TMS

δ++

(16)

δ–

–

(18)

Scheme 9

The formation of trisilylmethane derivatives proceeds equally well when in situ generated sila!ethene is treated with a proton donor reagent ð73JOM"162#030\ 74CRV308\ B!78MI 595!90Ł[ For example\trisilylated methanes "08# have been isolated in good yield from reacting tris"TMS#methylsiliconhalides with methanolic sodium methoxide[ The reaction is believed to proceed through an elim!ination\ analogous to E1 eliminations of alkyl halides\ involving synchronous attack of MeO− at aTMS group\ liberation of X−\ and formation of the transient silaethene followed by addition ofmethanol across the C1Si bond "Scheme 09#[ The compounds "TMS#2CSiPhMeF and "TMS#2CSi!PhCl1 react analogously to give "TMS#1CHSiPhMe"OMe# and "TMS#1CHSiPhCl"OMe#1ð67JOM"046#C49\ 79JOM"080#244Ł[ It should be noted that in contrast to the silicon species\ the ger!manium compounds "TMS#2CGeR1X undergo normal "though very slow# direct nucleophilic sub!stitution at germanium ð79JOM"191#046Ł[

SiR

R

TMS

TMS

(19)TMS

TMS

SiR2X

TMS

TMS

SiR2OMeMeOH/NaOH

refluxTMS

MeOH

>60%

R = Me or Ph, X = Cl, Br or IR = Ph, X = F

Scheme 10

The ene reactions of silaethenes are also potentially useful for the preparation of functionalizedtrisilylmethanes[ Thus silaethene "05# reacts with isobutene at −09>C to give compound "19#[ Asimilar reaction occurs between "05# and other alkenes ð76ZN"B#0951Ł[ The rates of these reactionsare sensitive to steric hindrance but even the sterically encumbered silaethene "06# still adds propene


and isobutene ð75CB0356Ł[ The ene reactions of silaethenes with carbonyl compounds containing aproton in the a!position such as acetone\ cyclohexanone\ or ethyl acetate are also potentially usefulfor the preparation of functionalized trisilylmethanes "Scheme 00# ð72AG"E#0994\ 75CB0356\ 75JOM"204#8\76ZN"B#0951Ł[

TMSSi

TMS

Si

TMS

TMS Me

Me

MeMe

(20)

TMSSi

TMSMeMe

R

XSi

O

TMSMeMe

R

Si

TMS

X

Me

Me

R

(16) X = TMS(17) X = TBDMS

ether–78 to 20 °C

X = TMS

(16)

R = Me

O

R

ether, –78 °C

Scheme 11

"ii# Compounds with an Si2C function as part of one or more rin` systems

These can be prepared by a variety of methods of which the main ones are]"a# reductive silylation of a halohydrocarbon with a suitable halosilane "the MerkerÐScott

procedure#^"b# metal!induced coupling of chloromethylchlorosilanes^"c# reaction between a lithiated cyclic carbosilane and a silicon electrophile^ and"d# cycloaddition to multiple carbonÐsilicon bond bearing silicon substituents at the carbon atom[Synthesis of the tricyclic carbosilane "11# was accomplished by preparing the cyclic carbosilane

"10# and reacting it with bromoform and lithium metal "Equation "5## ð61ZAAC"289#046Ł[ A similarreductive silylation route with silane "12# gave the tetrasilabicycloð1[1[1Łoctane "13# "Scheme 01#ð61ZAAC"289#080Ł[ 0\2!Disilabicycloð0[0[9Łbutane "15# has been synthesized by a method involving thelow temperature reaction of carbosilane "14# with butyllithium in THF "Scheme 02# ð70ZAAC"364#76\73JOM"160#096Ł[ From the trisilylmethane "16# tris"dimethylchlorosilyl#ethene results in a remarkableyield "×74)# presumably via a silacyclopropane intermediate "Scheme 03# ð66ZAAC"329#010Ł[

Si Si

Si

Si SiSi

Me Me

Me Me

Me

MeMe

Me

Me

Si

Si

Si

Si

Si

Si

Me

Br

Br

MeMe

Br

Me

MeMe

Me

Me Me

HCBr3/Li

(21) (22)

(6)

Synthesis of cyclocarbosilanes including an Si2C unit from {{carbon anion|| precursors appearsto be a generally applicable method that is primarily limited by the availability of suitablestarting materials ð63TCC32Ł[ Typically a lithiated cyclocarbosilane is generated in solution andthen treated with the appropriate silylating reagent[ For example\ the conversion of 0\2\4!trisilacyclohexane "17# into trisilylated derivative "18# has been achieved by lithiation withBunLi:TMEDA complex followed by treatment with a chlorosilane "Scheme 04# ð72ZAAC"386#10Ł[

Among the many reactions of unsaturated siliconÐcarbon compounds which lead to cyclo!carbosilanes\ several include photochemical or thermal generation of silaethenes and their sub!sequent conversion into cyclic compounds containing an Si2C unit[ Thus irradiation of a benzenesolution of "29# with a high!pressure mercury lamp gave 0\1!disilacyclobutane "20# in 89) yield"Scheme 05# ð68JA0237\ 70JA1213Ł[

Both photolysis and thermolysis of bis"TMS#diazomethane produce a carbene which rearranges


SiPhMe2

SiMe

SiPhMe2

SiPhMe2Br SiPhMe2 Li SiPhMe2

HCBr3

THF, 0 °C25%

(23) (24)

SiMe2BrSiMe

SiMe2Br

SiMe2Br

Si

SiSi

Si

Me

Li

ether, –10 °C

Br2

CCl4, 30 °C95%

MeSiCl3

79%

Scheme 12

Si

Si

TMS

Cl

Cl

TMS

Me Me

Me Me

TMS SiMe2Cl

Cl Li

TMS SiMe2Cl

Cl Cl

Si

Si

TMS TMS

MeMe

Me Me

(25)

BunLi

THF/ether–100 °C

(26)

Scheme 13

SiMe Me

Me2ClSi Cl

Me2ClSi SiMe2CHCl

Me2ClSi Cl

Me2ClSi Cl

SiMeMe

–

ClMe2ClSi

Me2ClSiMe2ClSi

Me2ClSi SiMe2Cl

BunLi

ether/pentane–100 °C

(27)

85%

Scheme 14

SiSi

Si

MeMe

Me

Me

SiSi

Si

MeMe

Me

Me

LiMeMe

SiSi

Si

MeMe

Me

Me

TMSMeMe

(28)

TMS-ClBunLi/TMEDA

hexane

Me Me

(29)

Scheme 15

via methyl migration to silaethene Me"TMS#C1SiMe1[ The latter dimerizes to produce as the majorproducts cis! and trans!0\2!disilacyclobutanes\ Me"TMS#C"SiMe1#1C"TMS#Me "35)# ð79JA0473Ł[

Decomposition of compound "21# in the gas phase at 349>C a}ords product "22# via the cor!responding silaethene "Scheme 06# ð79JOM"075#298Ł[

Unsaturated systems of the type a1b\ a0b1c\ and a1b0c1d often combine with the C\C!disilyl!substituted silaethenes to give ð1¦1Ł!\ ð1¦2Ł!\ and ð1¦3Ł!cycloadducts containing Si2C units


SiSi

Ph

Ph

Ph Ph

TMS TMS

•

TMS

TMSSi Si

TMS

TMS TMS

TMS

Ph

Ph

Ph

Ph

Si•

TMS

TMS

Ph

PhSi

Ph

Ph

1/290%

TMSTMS

Scheme 16

(31)

(30)

hν

benzene, 20 °C

1/2

Si

TMS

TMS

(33)(32)

450 °CPh

PhTMS TMS

SiPh2FTMS

Si

SiPh

Me

MeMe

TMS

Scheme 17

ð73JOM"162#030Ł[ However\ practically all such reactions are only useful for speci_c derivatives orspeci_c groups of compounds[ Characteristic examples are given in Scheme 07[ The review byWiberg contains experimental details for the preparation of compounds "23#Ð"25# ð73JOM"162#030Ł[

Scheme 18

N

Si Me

Me

TMS

TMS

Si

TMS

TMS

Me

Me

N

Si

RR R R

NN

Z

Ph

TMSTMS Me

Me

(34)

(35)

Ph

ZSi

MeMe TMS

TMS

(36)

Z = O-, N-TMS

(16)

5[95[1[0[1 Functions bearing three borons

Tri!coordinate boron compounds\ BX2\ have a formally vacant orbital in the valence shell andare isoelectronic with the corresponding carbocations\ ¦CX2[ For triorganoboranes\ BR2\ there islittle possibility of populating this orbital by conjugative interaction "apart from hyperconjugation#with the substituents[ It is hardly surprising\ therefore\ that the simple tris"boryl#methanes such asHC"BH2#2 or HC"BMe2#2 are highly reactive\ unstable compounds[ This is also a major reason why


compounds of the type HC"BX1#2 that have actually been isolated\ have X groups in which aheteroatom capable of donating p!electron density is bound to boron[ The preparation and proper!ties of the species containing a B2C function vary a great deal with the structural type and characterof substituents\ and they will therefore be discussed under these headings[

"i# Tris"dihaloboryl#methanes\ RC"BHal1#2

The homologous C"BHal1#nHal3−n "n�0Ð3# were observed in the reaction between various boronhalides and carbon vapor generated from a carbon arc[ In this manner B1Cl3 a}orded a mixtureof C"BCl1#3\ ClC"BCl1#2\ and Cl1C"BCl1#1^ and BCl2 yielded the last two compounds as well asCl"Cl1B#C1C"BCl1#1[ Compounds ClC"BCl1#2 and Cl1C"BCl1#1 are thermally unstable above−19>C[ From the reaction of B1F3 and carbon vapor\ C"BF1#3 was only isolated in a small amountð58JCS"A#0771Ł[

The method for synthesizing tris"dichloroboryl#methane "26# is the exchange reaction of tris!"dimethoxyboryl#methane with boron trichloride and a catalytic amount of lithium borohydride"Equation "6##[ Reaction conditions were found to be critical^ it is important that a large excess ofboron trichloride be used and that the crude product be distilled rapidly\ since it is particularlyunstable to be stored ð62IC1361Ł[ Reaction of structure "26# with boron tribromide failed to lead topure tris"dibromoboryl#methane\ HC"BBr1#2\ but bromineÐchlorine exchange did occur and theHCB2 signal of HC"BBr1#2 appeared in the NMR spectrum ð61MI 595!90\ 62IC1361Ł[

B(OMe)2

(MeO)2B B(OMe)2

BCl2

Cl2B BCl2

BCl3/LiBH4(cat.)

31%

(37)

(7)

There are several reports in the literature that the addition of boron halides across multiple bondsleads to 0\0!diboryl!substituted alkanes ð71HOU"02:2a#0\ 80CRV24Ł[ Thus\ diboron tetrachloride addstwice to alkyne giving CH"BCl1#1CH"BCl1#1\ and dehydroboration of alkynes with dichloroboraneethyl etherate "BHCl1=Et1O# in the presence of BCl2 yields `em!diboryl compounds RCH1CH"BCl#1ð65JA0687Ł[ However\ despite many unique advantages associated with hydroboration and halo!boration\ the synthesis of 0\0\0!tris"dihaloboryl#alkanes via alkynes has not yet been realized[

"ii# Tris"dialkoxyboryl#methanes\ RC"B"OAlk#1#2

These compounds have also been called methanetriboronic esters[ The compound HC"B"OMe#1#2is named in Chemical Abstracts as methylidynetrisboronic acid hexamethyl ester[

The preparation and properties of tris"dialkoxyboryl#methanes have been reviewed up to 0865ð64S036\ B!66MI 595!90Ł[ Tris"dimethoxyboryl#methane "27# is readily available on a large scale bydirect reaction of chloroform with dimethoxyboron chloride and lithium metal in THF "Equation"7## ð57JA1083\ 58JOM"19#08Ł[ The procedure has been described in detail^ the product is isolatedby distillation ð64S036Ł[ 0\0\0!Trichloroethane and a\a\a!trichlorotoluene react analogously\ butattempts to condense polyhalomethanes with bis"dimethylamino#boron chloride\ ClB"NMe1#1\ havefailed[

Cl

Cl Cl

B(OMe)2

(MeO)2B B(OMe)2

ClB(OMe)2/Li

THF, –40 °C25–35%

(38)

(8)

Transesteri_cation of structure "27# with ethylene glycol in THF precipitates cyclic boronic ester"28# "74)# ð64JA4597\ 65JOM"009#14Ł[ Similarly the cyclic boronic esters "39# and "30# were formedfrom the tris"dimethoxyboryl#methane and pinacol or 0\2!propanediol in the presence of a catalyticamount of boron tri~uoride etherate ð69JOM"13#152\ 63JOM"58#34\ 64JOM"82#10Ł[ These compounds


proved to be more stable than their acyclic analogues and better yields of products have beenobtained from them in a wide variety of reactions ð64S036Ł[

B

B B

OO

O

OO

O

(39)

B

B B

OO

O

OO

O

(40)

B

B B

(41)

OO

O

OO

O

The transborylation reaction of tris"dimethoxyboryl#methane "27# with triethylborane in thepresence of {{ethylborane|| provides a route to the only known 0\0\0!tris"dialkylboryl#methane "32#[The initially formed mixed triborylmethane "31# undergoes transformation to the compound "32#on heating at about 099>C "Scheme 08# ð64LA0228Ł[ The full scope of this reaction\ however\ remainsto be explored further[

B(OMe)2

(MeO)2B B(OMe)2

B(OMe)Et

Et2B BEt2

BEt3/[>BH] BEt3/[>BH] BEt2

Et2B BEt2B(OMe)3

(38) (42) (43)

Scheme 19

The alkylation of the anionic species derived from methanetetraboronic esters ð62JA4985Ł byalkyl halides was found to proceed readily\ but unfortunately the reaction leads to a mixture ofmonoalkylated and dialkylated derivatives\ as illustrated in Scheme 19 ð69JOM"13#152\ 64S036Ł[ Evi!dently the initially formed 0\0\0!triborylalkane "35# is able to transfer a dimethoxyboryl groupto tris"dimethoxyboryl#methide ion "34#\ thus undergoing disproportionation[ Condensation oftriborylmethide anions with aldehydes and ketones a}ords alkene!0\0!diboronic esters "37#\ pre!sumably via the unstable cyclic borate anion "36# "Scheme 10# ð69JOM"10#P5\ 63JOM"58#42Ł[ Thereaction is a general one and tolerates other functional groups\ including a!chloro\ carbethoxy\ ortertiary amino substituents ð63JOM"58#52\ 64JOM"82#10\ 67JOC849\ 67JOM"041#0Ł[

(MeO)2B B(OMe)2

B(OMe)2(MeO)2B

(MeO)2B B(OMe)2

B(OMe)2Li

(MeO)2B B(OMe)2

B(OMe)2RMeLi

THF, –70 °C

RI (45)

–(44)

(MeO)2B B(OMe)2

LiR

(MeO)2B B(OMe)2

RRRI

(44) (45) (46)

R = Me, Et

Scheme 20

OB(OR)2 = B(OMe)2, B

O O

O

, BO

, BO

(RO)2B B(OR)2

O BLi B(OR)2

OR

OR

B(OR)2

B(OR)2

R1

R2R2

R1 B(OR)2

B(OR)2

Scheme 21

–

(47)

R1COR2

THF, –70 °C

41–93%

(48)


Finally\ it should be noted that metallation of triborylmethide anions with Ph2ECl\ where E�Si\Ge\ Sn\ or Pb\ provides a useful method for the synthesis of compounds Ph2EC"B"OR#1#2 ð58JA5430\62JA4985\ 62JOM"46#114\ 62JOM"46#120\ 63JOM"58#52Ł[

"iii# Boracycloalkanes involvin` a B2C function

There are several speci_c methods which are useful for the preparation of boracycloalkanescontaining a B2C unit[

Compounds "49# are obtained in up to 49) yield via the isolable 0\0!bis"dialkylboryl#!0!alkenes"38# from dialkyl"0!alkynyl#boranes and dialkylboranes "Scheme 11# ð53TL0556\ 64LA0228\73HOU"02:2c#051Ł[ These have been classi_ed as pentaalkyl!0\4!dicarba!closo!pentaboranes"4#\ butthe valency requirements of all atoms can be satis_ed without the need to involve electron!de_cientbonding ð69JA3047\ 63JCS"D#554\ 80CB1534Ł[

HBR12

R12B

R12B R2

HBR12

5 °CBB

BR1R1

R2

R1

R2R12B

R1 = Me, Et, or PrR2 = H, Me, or C6H13

(49)

(50)Scheme 22

R2

An e.cient synthesis of 1\2\4\5!tetraborabicyclo ð1[0[0Łhexane "40# utilizes the reaction of 0\0\1\1!tetrakis"chloro"diisopropylamino#boryl#ethane with sodium:potassium alloy in benzene "Equation"8## ð89AG"E#181Ł[

B

B B

B

B

B BR

R

RR

B

HH

R

Cl

R

Cl

R

Cl

R

Cl

Na/K

benzene, reflux73%

(51)R = Pri2N

(9)

Sealed!tube pyrolysis of BMe2 permits isolation of 1\3\5\7\8\09!hexaboraadamantane "41# in 14)yield ð62CC421\ 64JCS"D#037Ł[ This boronÐcarbon cage compound appears to be unique in having astoichiometry expected of a carborane and yet not possessing the usual carborane type of structureð66JCS"D#025Ł[ The ethyl analogue "42# is produced by thermal decomposition of the tris!"diethylboryl#methane or polyboryl compounds\ themselves obtainable by hydroboration of dial!kyl"alkynyl#boranes ð64LA0228Ł[

B BB

BB

BRR

RRR

R

(52) R = Me(53) R = Et(54) R = But

(55) R = Cl(56) R =Br(57) R = Me2N

Pyrolysis of alkyldichloroboranes such as MeBCl1\ Cl1BCH1CHBCl1 or "Cl1B#2CH at 349>Cforms hexachlorohexaboraadamantane "44# "4Ð17)#[ The synthesis of hexabromohexabora!adamantane "45# has been achieved by heating Me1BBr or MeBBr1 to 419>C[ The reactions ofstructure "44# with t!butyllithium and diethylamine at −59>C lead to the formation of the cor!responding t!butyl! "43# and dimethylamino! "46# derivatives ð78JOM"256#08Ł[

Another route to compounds possessing C3B5Ðadamantane structure uses dimerization of theC1B2!closo!carbaborane "49# by treatment with potassium followed by iodine "Equation "09##ð74AG"E#215Ł[


(50)

2K/I2

THF, 20 °C, 4 d27% B B

B

BB

BEtEt

BBB

EtEt

Et

EtEt

Et (10)

(58)

The formation of compounds C5H8=x"BNPri1# "x�0Ð5# from the reaction of benzene with dich!

loro"diisopropylamino#borane and sodium:potassium alloy in 0\1!dimethoxyethane has been con!_rmed by mass spectroscopic studies[ The compound with x�2 was separated from the reactionmixture and identi_ed as 1\7\8!triborabicycloð2[2[0Łnona!2\5!diene!1\7\8!triamine "48# "Equation"00## ð77JOM"236#00Ł[ Similarly\ 0\3\5!triboraspiroð3[3Łnona!1[7!diene "59# has been isolated from thereaction of benzene with subvalent boron species ð89CC630Ł[

BBPri

2N

NPri2

B NPri2

(59)

2n Na/Kn Cl2BNPri

2

–2n MICl(DME)

C6H6•xBNPri210n (11)

(60)

B

B

B

Pri2N NPri

2

Pri2N

Addition of a mixture of bis"TMS#butadiyne or 1\4!dimethyl!1\3!hexadiene with Pri1NBCl1

to Na:K alloy in hexane gave the 1\3\4!triborabicycloð0[0[0Łpentane "23)# "Equation "01##ð81CB0796Ł[

Na/K,Cl2BNPri2

hexane, RTTMSTMS

BB

Pri2N

NPri2TMS

NPri2

(12)

TMS

A unique method for the synthesis of compounds containing a B2C function utilizes low!coor!dinate boron derivatives[ 1!Boranediyl!0\2!diboretanes "50# smoothly add ethanol to give com!pounds of structure "51# in quantitative yields "Equation "02## ð78AG"E#670Ł[ Despite considerablesynthetic potential\ this method is clearly limited by the availability of the requisite boron substrates[

EtOH

100% (NMR)

B

B

Ar

Ar

B ArTMS

TMS

B

B

Ar

Ar

TMS

TMS

Ar

OEt

(61) (62)Ar = 2,4,6-Me3C6H2, 2,3,5,6-Me4C6H

(13)


5[95[1[0[2 Functions bearing three germaniums

In contrast to numerous publications dealing with trisilylmethanes\ literature reporting tri!germylmethyl derivatives are sparse[

It is curious that straightforward synthetic routes are known for compounds containing Si2Cfunctions but not for those with functions bearing three germaniums[ It appears that many of themethods suitable for the synthesis of mono! and bisgermylalkanes are ine}ective or not applicableto trigermylmethanes[ For example\ although the compound "Et2Ge#1CH1 was successfully obtainedby the reaction of triethylgermylpotassium with dichloromethane\ attempts to prepare "Et2Ge#2CHby a similar route have failed\ because the metalÐhalogen exchange reaction\ followed by conden!sation\ predominated ð56TL0332Ł[ The reaction of Ph2GeNa with chloroform in liquid ammonia wasalso unsuccessful[ Only one of the three chlorine atoms bonded with a carbon is quantitativelyreplaced by the Ph2Ge group^ a second chlorine is largely substituted while the third is completelyreplaced by hydrogen ð21JA0511\ 41JA0307Ł[

The _rst stable compound with a Ge2C function\ 0\4\4\4!tetrakis"trimethylgermyl#!0\2!pentadiyne"53#\ has been synthesized by condensation of the tetralithium compound from 0\2!pentadiyne withchlorotrimethylgermane "Scheme 12# ð62JA2213Ł[ Reaction leads to a mixture of two pergermylatedisomers\ "52# "31)# and "53# "06)#\ which were separated by preparative gas chromatography[ Themethod is only of limited value\ since polylithiated species are not readily available[

BunLi/TMEDA

n-butane

Me3GeCl

THFC5Li4

(63) (64)Scheme 23

GeMe3

•

Me3Ge

Me3Ge

+ Me3Ge

GeMe3

GeMe3

GeMe3

GeMe3

0\0\0!Tris"triethylgermyl#acetone was reported to form in very low yield from the reaction oftriethylgermyldiazoacetone with an equimolar amount of bis"triethylgermyl#mercury in the presenceof metallic copper ð66JOM"031#044Ł[ Although this transformation is of some mechanistic interest\ itdoes not provide a synthetically viable route to trigermylmethyl species[

The more ~exible and useful route to 0\0\0!trigermylalkanes involves stepwise base!assistedintroduction of an R2Ge group into compounds containing an activated methyl group[ Sato and co!workers have prepared a series of trigermylacetic acid derivatives using this approach ð77JOM"243#044\77OM628\ 89OM0214Ł[ Some of these reactions are outlined in Schemes 13\ 14\ and 15[ The reactionof the lithium salt of trimethylgermylacetonitrile with bromotrimethylgermane is not straight!forward and leads to a mixture of germylated species "Scheme 13#[ Detailed investigation showedthat the trimethylgermylacetonitrile anion readily reacts with Me2GeCH1CN via intermolecularanionic rearrangement of the Me2Ge group to give bis"trimethylgermyl#acetonitrile anion andMeCN[ Anion "Me2Ge#1C−CN\ prepared from structure "55# with an equimolar amount of lithiumdiisopropylamide "LDA#\ is stable enough at low temperature[ However\ treatment of "55# with a9[4 molar equivalent of LDA gives a mixture of germylated products ð76SC0162Ł[

+CN

Me3Ge GeMe3 Me3Ge GeMe3

GeMe3NC

i, 2 BunLiii, 2 Me3GeBr

ether, –78 °C

Me3GeBr/Zn

benzene/THF71% (65)

Cl CN Me3Ge CN

Scheme 24

(66) (67)

Trimethylgermylation of ethyl lithioacetate gave a high yield of ethyl"trimethylgermyl#acetate"57#[ The use of excess amounts of LDA and Me2GeCl a}orded ethyl tris"trimethylgermyl#acetate"58# in high yield "Scheme 14# ð77OM628Ł[ Under approximately the same conditions\ the tris!"trimethylgermyl#acetamide "69# has been obtained in 61) yield "Scheme 15# ð77JOM"243#044Ł[


(68)

i, 2 LDAii, 2 Me3GeCl

THF –78 °C 82%

Me3Ge COOEt

i, LDAii, Me3GeCl

ether, –78 °C 78%

O

OEtMe3Ge

GeMe3Me3Ge

MeCOOEt

(69)Scheme 25

i, BunLiii, Me3GeCl

0 °C, 72%

O

NMe3Ge

GeMe3 i, 2 LDAii, 2 Me3GeCl

THF –78 °C 82%

N

O

O

NMe3Ge

GeMe3Me3Ge

(70)Scheme 26

The LAH reduction of structure "58# gave a 67) yield of 1\1\1!tris"trimethylgermyl#ethanol\ andtreatment with n!butyllithium at room temperature a}orded an 75) yield of 0\0\0!tris!"trimethylgermyl#!1!hexanone ð77OM628Ł[

5[95[1[0[3 Functions bearing mixed metalloids

Several procedures are available for the synthesis of compounds of the type RC"E0Xm#!"E1Xn#"E2X"m#n#\ where E0\ E1\ and E2�Si\ B\ or Ge\ but two groups of reactions are mostimportant[ The _rst group includes the reactions of organometallics RC"M#"E0Xm#"E1Xn# withinorganic or organoelement halides\ Xm"n#E2Hal\ and the second is the reactions based on unsatu!rated germanium or boron compounds containing elementÐcarbon double bond\ XmE0�C"E1Xn#"E2Xm"n##[

"i# Synthesis based on a!silyl!\ boryl!\ or `ermyl!substituted or`anometallics

Three typical examples illustrating this methodology are shown in Equations "03#Ð"05#ð65JOM"009#14\ 67JOM"042#142\ 78AG"E#44Ł[ The requisite organometallics can be obtained by methodswhich are discussed in Section 5[95[1[1[

MgCl

TMS TMS

GeCl4

ether, 80%

GeCl3

TMS TMS(14)

Li

TMS TMS

BCl3

ether, 20 °C38%

B

TMS

TMS

Cl

TMS

TMS(15)

Li

B B

Ph3GeCl

ether, 20 °C42%O

OO

O

GePh3

B B

O

OO

O

(16)

In principle\ the approach provides a general synthetic pathway to compounds containing mixedmetalloid functions\ but the correct choice of the reactants and reaction conditions is very important[The best results were obtained by the low temperature reaction of a functionalized organolithiumor organomagnesium compound with a metalloidal halide in ethereal or THF solution[ The group onmetalloid which is usually replaced includes Cl\ F\ RO\ or "TMS#1N ð75CB1855\ 78CB0946\ 80POL0042Ł[

Germanium chlorides react with a!silylated organometallics with retention of the oxidative stateof germanium[ For example\ treatment of GeCl1"diox# or Ge"N"TMS#1#1 with an equimolar amountof MgCl"CH"TMS#1# or Mg"CH"TMS#1#1 in ether leads to the bis"bis"TMS#methy#lgermylene "60#in 59Ð69) yield "Equation "06## ð65CC150\ 65JCS"D#1157\ 71CC0396\ 73CC379\ 75JCS"D#0440Ł[ The relatedpreparation of bis"TMS#methyl"pentamethylcyclopentadienyl#germylene "61# has been described


starting from Me4C4GeCl and "TMS#1CHLi "Equation "07## ð75OM0833Ł[ It should be noted thatbis"TMS#methyl!substituted germylenes such as structures "60# and "61# and "TMS#2CGeCH"TMS#1ð80OM0536Ł represent a unique class of compounds\ which can exist as monomers "carbene ana!logues# or dimers "alkene analogues# depending on the structure and phase state ð80CRV200Ł[ If anelectrophile such as iodine\ methyl iodide\ acetyl chloride\ a diazoalkane\ or a diazidosilane isadded to the germylene "61#\ then high yields of the oxidative addition products containing theGe"IV#CH"TMS#1 unit are obtained ð75OM629\ 83OM323\ 83OM325Ł[ A reaction of germylene "60#with an alcohol provides the functionalized germane HGe"CH"TMS#1#1OEt ð70JOM"101#C3Ł[

[(TMS)2CH]2Mg

ether, 60–70% TMS

TMS Ge TMS

TMS(71)

GeCl2(diox) (17)

(TMS)2CHLi

benzene/ether–80 °C, 76%

Me5C5Ge TMS

TMS(72)

Me5C5GeCl (18)

"ii# Synthesis based on low!coordinate boron and `ermanium derivatives

C\C!Disilyl!substituted methyleneboranes\ XB1C"TMS#1 ð82AG"E#874Ł\ and germaethenes\X1Ge1C"SiR2#1 ð73JOM"162#030\ 89CRV172Ł\ provide access to a variety of compounds containingmixed metalloid functions\ but the scope of the reactions is restricted to the preparation of speci_cpolyfunctional compounds[

At a temperature of 499Ð599>C methyleneboranes "62# and "63# undergo rearrangement intocyclic compounds in excellent yield ð89CB636Ł[ In analogous conditions the methyleneborane "64#is transformed to an azasilaboratedine "Scheme 16# ð78CB484Ł[

Scheme 27

B

TMS

TMSR

560 °C

R = Ph, 79%

580 °C

R = PhCH2, 92%

520 °C

R = Pri2N, 46%

Si

B

Si

B

Me

TMS

Me

TMS

N

B

Si Me

Me

Me Me

MeMe

Pri

TMSMe

(73) R = Ph(74) R = PhCH2(75) R = Pri

2N

Treatment of the trisilyl"germyl#methane "65# with CsF in DIGLYME leads to a compound ofstructure "67#[ The reaction is believed to take place by initial formation of the unstable germaethene"66#\ which because of steric hindrance\ cannot undergo cyclodimerization and looses a TMS groupto give a second transient germaethene "Scheme 17# ð72IZV848Ł[

CsF

DIGLYME48%

TMS TMS

GePh2ClTMSGe

TMS

TMS Ph

PhGe

TMS Ph

Ph Ge

Ge

Ph Ph

PhPh

TMS TMS

(76) (77) (78)

Scheme 28


A variety of disilyl"boryl#methanes has been prepared by making use of the high reactivity of theB1C double bond towards protic agents and organolithium compounds ð82AG"E#874Ł[ Some ofthese reactions are outlined in Scheme 18 ð76CB0958\ 78CB484Ł[ Borinanes "79# were obtained fromthe addition of HCl or HN"TMS#1 to the B1C bonds of boranediylborinanes "68# "Equation "08##ð81AG"E#0273Ł[ A related preparation of the 0\2!diboretane "71# has been described starting fromgermaethene "70# "Equation "19## ð76AG"E#687Ł[

HX

X = Hal, RO, R2N

B

TMS

TMS

Pri2N

B

X

Pri2N TMS

TMS

i, MeLi/TMEDAii, H+

hexane, –78 °C 79%

B

Me

Pri2N TMS

TMS

Scheme 29

HXBBTMS

TMS

BTMS

TMS

RR

R

B(X)R

(79) (80)

R = But, 2,3,5,6-tetremethylphenylX = Cl, (TMS)2N

(19)

(20)HCl

TMS

TMS

B

B

R

R

GeX2ClTMS

TMS

B

B

R

R

Ge

X

X

(81) (82)

R = But, X = (TMS)2N

Germaethene "72# generated as a reaction intermediate by thermal elimination of LiCl fromMe1ClGe0C"Li#"TMS#1\ can be converted into various compounds containing an Si1"Ge#C functionand in some cases this provides the best route to the new species "Scheme 29# ð75CB1855\ 75CB1879\76CB0192Ł[ Compound "74# has been synthesized by a method involving the low temperature reactionof kinetically stabilized germaethene "73# with methanol "Equation "10## ð80POL0042Ł[

MeOH

ether, –20 °c81%

GeTMS

TMS

TMS

TMS

TMS

TMS

Ge

TMS

TMS

OMe

TMS

TMS

TMS TMS

(84) (85)

(21)

"iii# Miscellaneous

0\2!Digermacyclobutane "75# has been found among the products of {{direct synthesis|| fromTMS"dichloromethyl#silane "Equation "11## ð61ZOB0410Ł[ The reaction of 0\2!diborete "76# withpotassium or lithium in THF leads to compounds 1K¦"76#1− or 1Li¦"76#1−\ which are protonatedwith "TMS#1NH to yield the 0\2!diboretane "77#[ Reaction of "76#1− with MeI a}ords the 0\2!diboretane "78# "Scheme 20# ð78CB0770Ł[

"Ge/Cu"

370–390 °C4%

Ge

Ge

Cl Cl

ClCl

TMS TMS

(86)

Cl

Cl TMS(22)


GeTMS

TMS

Me

Me

Me2Ge TMS

TMS

OMe

Me2Ge TMSTMS

R R

TMS

Me2Ge

TMS

TMS

TMSMeO

R R

MeOH

(R = H, Me, CMe=CH2)R

Scheme 30

OMe

(83)

(88) (89)

2K

THFB

TMSTMS

NR2R2NTMS

TMS B Cl

R2N

B

R2N

Cl

2M

THF2M+ (87)2–

2 MeIB B

NR2R2N

(TMS)2NH

TMSTMS

B B

TMSTMS

NR2R2N

(87)2–

Scheme 31

(87)

B

5[95[1[1 Functions Containing Metalloids and Metals

5[95[1[1[0 Functions bearing silicon"s# and metals"s#

This section is devoted to methods of preparing a!silylated organometallics having the generalstructure RC"SiX2#n"MLm#2−n\ where M is a metal\ n�0 or 1\ and R�H\ alkyl\ aryl\ or hetaryl[These compounds are of special interest due mainly to _ndings that silylmethyl groups like"TMS#1CH or "TMS#2C combine bulkiness with the capability to form strong metalÐcarbon bondsand that organometallic compounds bearing the polysilylmethyl group often possess unique proper!ties and have unusual structures ðB!74MI 595!90\ B!80MI 595!90Ł[ Although a!metallated organosilanechemistry has been reviewed extensively since the early 0879s ð79HOU"02:4#16\ B!70MI 595!90\ B!72MI595!90Ł\ polysilylated organometallics have received only passing comment within reviews with muchwider scope ðB!74MI 595!90\ 80COS"0#0Ł[

"i# Alkali metal and ma`nesium derivatives of silylmethanes

In the mid 0889s there are four general methods for the production of compounds of this type[These are]

"a# metalÐhydrogen exchange reactions of silylmethanes with basic metal!containing reagents^"b# oxidative metallation of halo"silyl#methanes^"c# organometallic addition to vinylsilanes^ and"d# transmetallation of an already a!metallated organosilanes[Representative examples illustrating the synthesis of alkali metal and magnesium derivatives of


silylmethanes which have obvious potential synthetic utility are given in Table 1[ A few of thesilylmethyl derivatives of the alkali metals display unique aggregate structures and these are discussedby Williard ð80COS"0#0Ł[

Table 1 Preparation of trisilylmethyllithium derivatives of the alkali metals and magnesium[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐCompound Method of preparation Reaction conditions Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ"TMS#1CHLi "TMS#1CH1¦ButLi THF:HMPA "ca[ 3 ] 0#\ 66CB741\ 79JA0473

−67>C"TMS#1CHLi "TMS#1CH1¦BunLi¦TMEDA hexane\ 01 h\ 14>C 71CC0212"TMS#1CHLi "TMS#1CH1¦BunLi¦PMEDA hexane\ 9[4 h\ 19>C 71CC0212"TMS#1CHLi "TMS#1CHCl¦Li ether\ re~ux 65JCS"D#1157\ 79JA0473"TMS#1CHLi "TMS#2CH¦MeOLi HMPA\ 19>C 62TL3082"TMS#"MeOMe1Si#CHLi "TMS#"MeOMe1Si#CH1¦ButLi pentane\ 19>C 78JOC0673"TMS#1CRLia "TMS#1CHR¦BunLi THF:hexane 75CC561"TMS#1CRLia "TMS#1CHR¦BunLi¦TMEDA hexane 73CC0697"TMS#1CRLia "TMS#1CHR¦BunLi hexane:ether\ 19>C\ 0 h 72CC0308\ 73CC0697"TMS#1CRLib "TMS#1CHR¦BunLi¦TMEDA hexane\ 19>C 73JCS"D#0790"TMS#1CHNa "TMS#2CH¦NaOMe HMPA\ 19>C 62TL3082"TMS#1CHK "TMS#1CHLi¦ButOK hexane\ 19>C\ 05 h 80OM0693"TMS#1CHMgCl "TMS#1CHCl¦Mg ether\ re~ux\ 3 h 80JOM"310#064ð"TMS#1CRŁ1Mga "TMS#1CHR¦MgBunBus heptane 75CC561TMS!CH"MgBr#1 TMSCHBr1¦Mg"Hg# diisopropyl ether 75TL5012*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐa R�1!pyridyl[ b R�3!methylphenyl[

"a# MetalÐhydro`en exchan`e[ The methylene group between two silicon atoms shows enhancedreactivity with respect to proton abstraction by strong bases\ therefore many bis"silyl#methanesundergo metalÐhydrogen exchange on reaction with alkyllithium reagents ð66CB741\ B!72MI 595!90\72ZAAC"386#10Ł[ In practice\ these reactions require strongly coordinating solvents or the use ofalkyllithiums in the activating presence of TMEDA or potassium t!butoxide[ The successful prep!aration of bis"TMS#methyllithium can be achieved from the bis"TMS#methane using t!butyllithiumin hexamethylphosphoramide "HMPA# ð62TL3082\ 63AG"E#72Ł\ t!butyllithium in THF with HMPAat −67>C ð66CB741\ 79JA0473Ł\ BunLi:ButOK reagent in THF solution ð80OM440Ł or the TMEDAcomplex of n!butyllithium in hexane ð71CC0212Ł[ The last procedure provides one of the simplestroutes to "TMS#1CHLi[ In addition\ a feature of the use of TMEDA is that it enables crystallinemonomeric lithium derivatives to be isolated[ Silylated product yields for the system TMS!CH1TMS:BunLi:ButOK were in the range 67Ð80) ð80OM440Ł[ Metallation of the carbosilane"TMS#1CHSiMe1CH1TMS gave\ as expected\ "TMS#1C"Li#SiMe1CH1TMS\ since the indicated car!banion is stabilized by three silyl groups[ Only monometallation could be achieved for thecarbosilane TMS!CH1SiMe1CH1SiMe2 ð80OM440Ł[ Poly"dimethylsilene#\ "Me1SiCH1#n\ the poly!mer formally derived from dimethylsilaethene\ Me1Si1CH1\ has been shown to be metallated byBunLi:ButOK in THF to give a polycarbosilane in which\ on average\ every fourth CH1 group inan SiCH1Si environment is metallated ð80OM440Ł[

Methoxydimethylsilyl"TMS#methyl lithium\ HC"Li#"TMS#SiMe1OMe\ a reagent useful for thedirect conversion of aldehydes and ketones to vinylsilanes\ is readily formed in hydrocarbon solventfrom the appropriate silane and t!butyllithium ð78JOC0673Ł[ Access to the p!xylene compound p!MeC5H3CH"TMS#1Li is possible by using BunLi:TMEDA in hexane ð73JCS"D#0790Ł[ However\organolithium tertiary amines reagents failed to yield the dilithium derivative from 0\3!bis"bis!"TMS#methyl#benzene ð73JCS"D#0790Ł[

Lithium t!butylbis"TMS#acetate\ "TMS#1C"Li#CO1But\ results from the appropriately substitutedacetate using LDA in THF at −67>C ð65TL1626\ 66JOC1927Ł[ This organolithium compound is auseful synthetic intermediate in the Peterson alkenation reaction ðB!72MI 595!90Ł[

Reaction of the pyridine functionalized bis"TMS#methane "89# with n!butyllithium in hexaneyields complex "80#\ whereas metallation of "89# with BunLi and TMEDA in hexane a}ords lithiumderivative "81#[ Both compounds contain unprecedented h2!azaallyl ligand geometries ð73CC0697Ł[Treatment of 1!bis"TMS#methylpyridine with BunLi in ether or THF yields binuclear complex "82#"Scheme 21# ð72CC0308Ł[

A procedure for the preparation of 1!lithio!0\0\2\2\4\4!hexamethyl!0\2\4!trisilacyclohexane by themetallation of cyclo!ðMe1SiCH1Ł2 with BunLi:TMEDA in hexane has been developed ð72ZAAC"386#10\81OM2353Ł[ The yields of monolithium derivative in this synthesis is very good\ but further met!allation did not occur at 19>C even when excess metallation reagent was used[ Similarly 0!TMS!0\2\4!trisilacyclohexane can be selectively metallated at the more sterically available ring proton^


N

Li Li

NTMS

TMS

TMS

TMS

N

Li

(TMS)2HC

:

N CH(TMS)2

N

Li

:

Me2N NMe2

(90)

(92) (93)

(91)

Scheme 32

TMS

TMS

TMS

TMS

BunLi in hexane 20 °C

BunLi in hexane, 20 °C+ TMEDA

BunLi in ether20 °C, 1 h

ether, 20 °C

however\ if not immediately quenched the kinetic product "83# rearranges to the more stablelithium derivative "84# "Scheme 22# ð72ZAAC"386#10Ł[ In contrast to 0\2\4!trisilacyclohexane\ 0\0\2\2!tetramethyl!0\2!disilacyclobutane "85# reacts with n!butyl\ methyl!\ and phenyllithium to open theSi1C1 ring ð64JCS"D#0323\ 89OM1566Ł[ Even so\ the solutions of 1!lithio!0\2!disilacyclobutane "86#could be prepared by the action of ButLi:TMEDA on "85# in hexane "Scheme 23# ð89OM1566Ł[ Inreactions of "86# with TMS!Cl\ Me1HSiCl\ Me2SnCl\ n!PrI\ XCH1CH1X "X�Br\ I#\ Me1S1\ and I1\the disilacyclobutane ring is retained while the methylene carbon atom is functionalized ð89OM1566Ł[

Si

Si

Si

TMS

Si

Si

Si

TMS

Si

Si

Si

TMS

LiBunLi/TMEDA

hexane, 20 °C

(94) (95)

Li

Scheme 33

MeLi

ether, reflux>74%

ButLi/TMEDA

hexane>60%

Me2Si SiMe2

Li

TMSMe

SiMe

Li

Me2Si SiMe2

(96)

(97)

Scheme 34

"b# Oxidative metallation of halo"silyl#methanes[ This is a superior method for generating avariety of silyl!substituted organometallics from readily available starting materials[ The synthesisis very simple to carry out in the laboratory and yields are normally excellent[ For example\chlorobis"TMS#methane reacts with lithium metal in ether to give the corresponding lithium deriva!tive in virtually quantitative yield ð65JCS"D#1157Ł[ The starting functionalized methane may be readilyprepared from CH1Cl1\ TMS!Cl\ and BunLi as shown in Scheme 24 ð60JOM"18#278\ 70SRI480Ł[ In theopinion of the present authors\ this route is best for the preparation of "TMS#1CHLi[ One limitationof this scheme is that the synthesis of compounds "TMS#1C"R#Li is di.cult or impossible if group


R is methyl or primary alkyl[ Thus the reaction of "TMS#1C"Me#Cl with lithium metal leads to"TMS#1C1CH1 and "TMS#1C"H#Me instead of the expected lithium species ð68ZAAC"337#39Ł[

BunLi

THF/Et2O/penatne–110 °C

BunLiCl Cl

TMS TMS

ClCl+ 2 TMS-Cl

TMS TMS

LiCl

TMS TMS

Cl Li

ether, reflux TMS TMS

LiEtOH

–100 °C78%

Scheme 35

The preparation of bis"TMS#methylmagnesium halides can be performed in ether or THF usinghalobis"TMS#methane and magnesium powder ð72POL180\ 75JCS"D#0440\ 80JOM"310#064Ł[

The method can be extended to the preparation of bis"metallated# silylmethanes[ Thus\ dili!thio"TMS#methane "87# was obtained by reaction of dichloro"TMS#methane with lithium vapor"Equation "12## ð73CC0553Ł[ It should be noted that an alternative approach to this compound isthe thermolysis of TMS!CH1Li ð77POL1912Ł[ The bulky TMS groups seem to prevent extensivepolymerization of the dilithium derivative[ In both preparations the only by!products were lithiatedmethanes and silanes[ No higher polymers such as those observed for "CH1Li1#n were seen ð73CC0553Ł[

TMS Cl

Cl Li (vapour)

700–720 °C10-4 Torr

TMS Li

Li

(98)

(23)

Bis"bromomagnesio#TMSmethane "88# has been prepared directly from the reaction of TMS!CHBr1 and magnesium amalgam in diisopropyl ether "69)# "Equation "13## ð75TL5012Ł[ In relationto CH1"MgBr#1\ compound "88# is less reactive^ this must be due to the anion!stabilizing e}ect ofthe TMS group and possibly to steric hindrance[

TMS Br

Br Mg/Br

Pri2O, 20 °C TMS MgBr

MgBr

(99)

(24)

"c# Or`anometallic addition to vinylsilanes[ While organolithium compounds and Grignardreagents will not\ in general\ add to isolated C1C double bonds\ they will add to the silyl!substitutedalkenes to form a!silyllithium or a!silylmagnesium derivatives ð41JA3471\ 43JOC0167\ 69CJC450\69TL0026Ł[ The examples provided in Scheme 25 illustrate the application of the method for thesynthesis of lithiated bis"silyl#methanes[ Compounds of structure "099# are prepared in more than89) yield ð63AG"E#72Ł[ The a!lithio derivative "090# can be trapped by trimethylsilyl tri~ate to givecompound "091#\ and is a useful silaethene precursor "Scheme 25# ð81ZN"B#794Ł[

TMS TMS

CH2O

TMS(100)

TMSLi LiTMS

R

RLi

TMS

TMS

R = Bun, Bus, or But

TMS TMS

Cl

TMS

TMS TMS

Cl

TMS

LiBut

TMS TMS

Cl

TMS

TMSButButLi

pentane, –78 °C

CF3SO2O-TMS

(101) (102)

Scheme 36

It has been established\ by analogy to 0\0!bis"TMS#ethenes\ that silaethenes\ germaethenes\ andtheir analogues add organolithium reagents to form the appropriate polyfunctional derivatives


ð73JOM"162#030\ 74OM228\ 80AG"E#82Ł[ For instance\ the lithium species "093# was generated as shownin Scheme 26 by addition of phenyllithium to a solution of stannaethene "092# ð80AG"E#82Ł[

TMS TMS

MeOHLiMe2PhSnSn

TMS

TMS PhLi

hexane, –78 °CMe

Me

TMS TMS

SnPhMe2

(103) (104)

Scheme 37

0\1!Dilithio"tetrakis"TMS##ethane "094# results directly from the reaction of tetrakis"TMS#ethylene with excess lithium metal in dry!oxygen!free THF "Equation "14## ð78JA2637Ł[ The structureof "094# has been unequivocally con_rmed by x!ray crystallography and chemical transformations[Treatment of the dilithium compound with H1O and D1O cleanly produced tetrakis"TMS#ethane"095#[ The reaction with paraformaldehyde a}orded alkene "096# "62)# probably via 0\1!anionicrearrangement of the silyl group "Scheme 27#[ After prolonged standing "8 days#\ quenching theTHF solution of "094# with water led to the formation of compounds "097# and "098# together withsmall amounts of cyclic compounds "009# and "000# "Scheme 28# ð82CL156Ł[ These reactions probablyinvolve intramolecular proton abstraction from a methyl group on silicon followed by subsequentanionic rearrangement[

2Li

THFTMS

TMS

TMS

TMS

Li

Li

TMS

TMSTMS

TMS

THF

THF(105)

(25)

X2O (X = H, D)

THF, –78 °C

HCOH

THF, –78 °CTMS

TMS

(105)

TMSTMS

TMS

XX

TMS

TMSTMS

(106)

(107)Scheme 38

TMS SiMe2

TMS

Me2Si

Me2Si

SiMe2

SiMe2Me2Si

TMS TMSTMS

TMSTMS

TMSTMS

TMS+ + +

i, THF/9 daysii, H2O, –78 °C

(108), 45% (109), 13% (110), 4% (111), 1%

(105)

Scheme 39

Similarly\ phenyl"tris"TMS#ethylene participates readily in oxidative metallation reaction to give0\1!dilithiophenyl"tris"TMS##ethane[ Hydrolysis of the dilithio derivative leads to the formation oftris"TMS#phenylethane\ Ph"TMS#CHCH"TMS#1\ in almost quantitative yield ð81CL756Ł[

"d# Transmetallation and related reactions[ There are several useful syntheses using trans!metallation reactions for the preparation of silylmethyl derivatives of alkali and alkaline earth metals[

Bis"bis"TMS#methyl#mercury\ which can be prepared from the Grignard reagent and mercury"II#chloride\ exchanges mercury with lithium and the heavier alkali metals "Equation "15## ð79POL1912Ł[This procedure has been shown to be a particularly clean method for the generation of a!silylcarbanions[ However\ the dangers inherent in handling volatile mercury compounds make this routesomewhat less than attractive[ Bis"TMS#methylpotassium can also be prepared by transmetallationof bis"TMS#methyllithium with potassium t!butoxide in hexane "71)# "Equation "16## ð80OM0693Ł[


Hg

TMS

TMS M (M = Li, Na, or K)

ether, 20 °C TMS TMS

M(26)2

TMS

TMS

ButOK

hexane, 20 °C, 16 h TMS TMS

K

TMS TMS

Li(27)

Also included in this category are desilylation of tris"TMS#methane with sodium methoxide inHMPA "Equation "17## ð62TL3082Ł[ The driving force for this reaction may be the formation of astrong Si0O bond of methoxytrimethylsilane[ Similar reactions occur with tetrakis"TMS#methaneand bis"TMS#methane ð62TL3082Ł[

NaOMe

HMPA, 20 °C TMS TMS

Na

TMS TMS

TMS(28)

Dibromo"TMS#methane has been shown to react with a zincÐcopper couple in THF to give thedizinc derivative "TMS#CH"ZnBr#1[ Transmetallation of the compound with magnesium metala}ords the Grignard reagent "TMS#CH"MgBr#1 ð61JOM"39#C42Ł[

"ii# Bis"TMS#methyl derivatives of transition metals and `roup 02 and 03 metals

Practically all compounds of the type RC"SiX2#1"MLm# containing a metal of which the elec!tronegativity is greater than those of lithium and magnesium\ have been prepared by transmetallationreactions starting from a!silyl!substituted organolithiums or Grignard reagents and inorganic ororganometallic halides[ A listing of many of these reactions is given in Table 2[ Some speci_cexamples are discussed below[

Lithium bis"TMS#methanide reacts with lanthanum aryloxides "Ln�La or Sm# under ambientconditions to yield Ln"CH"TMS#1#2*the _rst structurally characterized neutral homoleptic alkyl ofthe lanthanide metals ð77CC0996Ł[

The conversion of several bis"polymethylcyclopentadienyl#!stabilized lanthanide complexes intobis"TMS#methyl derivatives "001# has been achieved by a low!temperature reaction withbis"TMS#methyllithium[ E}orts to abstract a proton from the a!carbon atom of the lanthanidecomplex "001^ M�Lu# did not yield an alkylidene[ Rather\ a salt "002# was isolated which wasassigned a metallacyclobutane structure "Scheme 39# ð74JA7092Ł[

The bis"TMS#methylyttrium complex "003#\ which can be prepared from Cp�1YCl and"TMS#1CHLi\ readily undergoes insertion reactions into the s!yttriumÐcarbon bond to produce newmonomeric complexes\ such as "004# and "005#\ stabilized by Cp� ligands and "TMS#1CH group"Scheme 30# ð76OM0498Ł[

Compounds "006# have been prepared from the appropriate metallocene dichlorides and anequimolar amount of "TMS#1CHLi in ether[ Sodium amalgam in THF under dinitrogen smoothlyreduces the bis"TMS#methylzirconium"IV# metallocenes "006# to complexes of structure "007#\containing {{side!on|| bonded dinitrogen according to Scheme 31 ð68JOM"070#14Ł[ These resultsprovide a further demonstration that the bulky bis"TMS#methyl ligand may stabilize unusual metalcomplexes[

The preparation of bis"bis"TMS#methyl#manganese "008# was accomplished by treating anhy!drous manganese"II# chloride with the Grignard reagent in THF as indicated in Scheme 32[ Thiscompound has proved to be a useful agent for transferring the ligand "TMS#1CH from Mn toanother metal site[ Thus\ the yield of Pb"CH"TMS#1#1 obtained from structure "008# and PbX1

"X�Cl or N"TMS#1# is certainly superior to that achieved in the direct reaction between"TMS#1CHLi and PbX1 ð89JOM"283#46Ł[

Mononuclear cuprate "019# was prepared as its lithium crown ether salt by addition of theorganolithium reagent to CuBr in THF[ Its structure consists of a well!separated cation\ "Li"01!crown!3#1#¦\ and a cuprate anion "Equation "18## ð74JA3226Ł[


Table 2 Preparation of bis"TMS#methyl derivatives of transition metals and group 02 and 03 metals[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Silyl rea`ent YieldMetal substratea ðR�"TMS#1CHŁ Product ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐScCl2 RLi ScR2=1THF 63JOM"65#C34YCl2 RLi YR2 63JOM"65#C34YCp1�Cl RLi YCp1�R 58 75OM0615YCp1�"OAr#1 RK YCp1�"OAr#R 61 83OM58La"OAr#2 RLi LaR2 77CC0996ðLaCp1�Cl1Ł

−Li¦ RLi LaCp1�R 59 74JA7980CeCp�"OAr#1 RLi CeCp�R1 77CC851ðNdCp1�Cl1Ł

−Li¦ RLi NdCp1�R 79 74JA7980Sm"OAr#2 RLi SmR2 77CC0996ðSmCp1�Cl1Ł

−Li¦ RLi SmCp1�R 34 74JA7980ECl2 RLi ðER2ClŁðLi"THF#3Ł 67CC039YbCl2 RLi ðYbR2ClŁðLi"THF#3Ł 67CC039LuCl2 RK LuR2"m!Cl#K"OEt#1 80OM0693ðLuCp1�Cl1Ł

−Li¦ RLi LuCp1�R 53 74JA7980TiCl2"Me2N#1 RLi TiR2 5 67JCS"D#623TiCp1Cl1 RLi TiCp1R 52 66JA5534\ 67JCS"D#623ZrCl3 RLi ZrClR2 34 67JCS"D#623ZrCp1Cl1 RLi ZrCp1ClR 32 66JA5534ZrCp1?Cl1 RLi ZrCp1?ClR 32Ð68 68JOM"070#14\ 70JCS"D#703HfCl3 RLi HfClR2 42 67JCS"D#623HfCp1Cl1 RLi HfCp1R 26 66JA5534VCl2"Me2N#1 RLi VR2 03 67JCS"D#623VCp1Cl1 RLi VCp1R 31 66JA5534VCp1Br RLi VCp1R 79 66JA5534CrCl2 RLi CrR2 60 67JCS"D#623MnCl1 RMgCl MnR1=THF 61 89JOM"283#46CuBr RLi ðCuBrRŁLi 74JA3226ZnCl1 RLi ZnR1 67 80JOM"310#064ZnCl1 RLi:TMEDA ðZnR2ŁLi 62 82ZAAC"508#564CdCl1 RLi CdR1 23 67JOM"042#142HgCl1 RLi HgR1 86 67JOM"042#142HgCl1 "TMS#1CMeLi HgðC"Me#"TMS#1Ł1 23 67JOM"042#142HgCl1 RMgCl HgR1 66 55JOM"5#340HgCl1 R1Hg HgClR 61 55JOM"5#340HgBr1 RLi HgR1 05 69JOM"13#536HgBr1 R1Hg HgBrR 25 67JOM"042#142AlCl2 RLi AlClR1 36 67JOM"042#142AlCl2 RLi AlR2 58 78ZAAC"468#64"AlBrBut

1#1 RLi AlBut1R 59 81ZAAC"502#56

"AlBr1But#1 RLi AlButR1 67 80ZAAC"484#114"AlCl1#1CH1 RLi "AlR1#1CH1 34 89POL166GaCl2 RLi GaR2 71 79IC2526Ga1Br3 RLi GaR2 31 78JOM"253#178Ga1Br3"diox#1 RLi GaR1Br 43 81CB0436Ga1Br3"diox#1 RLi ðGaR1Ł1 52 78JOM"253#178InCl2 RLi InR2 89 79IC2526InPriCl1 RLi InCl"R#Pri

1 50 80ZN"B#0428In1Br3"TMEDA#1 RLi ðInR1Ł1 43 78JOM"257#028SnCl1 RLi SnR1 60 75JCS"D#0440\ 65JCS"D#1157"SnClðN"TMS#1Ł#n RLi SnR1 60 65JCS"D#1157SnðN"TMS#1Ł1 RLi SnR1 08 65JCS"D#1157SnCl3 RLi SnCl1R1 73 75JCS"D#0440\ 71CC0396PbCl1 RLi PbR1 2 65JCS"D#1157*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐaAbbreviations] Ar�1\5!But

1C5H2\ Cp�h!C4H4\ Cp��h!C4Me4\ Cp?�h!C4H3X "X�H\ Me\ Et\ Pri\ But\ or TMS#[

Studies in the 0879s and early 0889s on the transmetallation reactions of nitrogen!functionalizedlithium bis"TMS#methanide "82# have yielded a series of molecules with unusual bonding con!_gurations[ For example\ the reaction of 1!bis"TMS#methylpyridine with butyllithium in THFfollowed by CuCl\ yields a binuclear complex "010# in which the metal is not involved in electron!de_cient bonding ð72CC0308Ł[ The silver"I# bis"TMS#methyl derivative "011# was prepared by asimilar method "Scheme 33# ð73CC501Ł[ The thermally stable N!functionalized bis"TMS#methylcobalt"II# complex has been prepared by reacting the lithium derivative "82# with cobalt"II#chloride in ether ð82JOM"332#C28Ł[ An x!ray structural study has revealed a centrosymmetric molec!ular skeleton in which a pair of pyridine ligands are trans!chelated to the central planar four!


Me2SiCp*2M

ButLi/TMEDA

hexane (M = Lu)TMS

TMS(TMS)2CHLi[Me2SiCp*

2MCl2]–Li(THF)+2

Me2SiCp*2Lu Si

Me

Me

TMS

–

Li(TMEDA)+3

(113)

M = Nd, Sm, or Lu

Scheme 40

(112)

TMS TMS

YCp*2N

ButTMS

TMS Y(NCBut)Cp*2

TMS

TMS

OYCp*2

O 2ButCN

toluene, 20 °C76%

CO2

benzene, 20 °C27%

(116) (114) (115)

Scheme 41

Na/ –Hg/N2

THF, 20 °CZr(η-C5H4R)2(N2)

TMS

TMS(TMS)2CHLi

ether, 20 °CZr(η-C5H4R)2Cl

TMS

TMS(Zr(η-C5H4R)2Cl2)

(117) (118)R = H, MeScheme 42

Sn[N(TMS)2]2

pentane, –10 °C71%

PbCl2

hexane, 20 °C64%

(119)

1/2 Sn2[CH(TMS)2]4

Pb[CH(TMS)2]2

MnCl2 Mn[CH(TMS)2]2(THF)[Mg(TMS)(µ-Cl)(THF)]2

THF, 20 °C, 18 h72% (119)

Scheme 43

CuBr Li(12-crown-4)2+

(TMS)2CHLi/12-crown-4

THF/toluene/hexane

CuBr

TMS TMS

–

(29)

(120)

coordinate cobalt"II# atom[ The complexes "M"NC4H3C"TMS#1!1#1#\ where M�Zn\ Cd\ or Hg\accessible from structure "82# and MCl1\ are mononuclear metal"II# alkyls in which the dative metalÐnitrogen interactions progressively weaken in the sequence Zn×Cd×Hg ð75CC561\ 82JCS"D#1542Ł[Monomeric 1!pyridylbis"TMS#methyltin"II# compounds of structures "012#Ð"014# were preparedfrom "82# and SnCl1 or Sn"N"TMS#1#1 "Scheme 34# ð77CC225Ł[

Bis"1!pyridylbis"TMS#methyl#stannylene "013# upon treatment with aryl azides forms the 0!aza!7!stannabicycloð2[1[9Łocta!1\3\5!triene system "015# via stannaimine intermediate "Scheme 35#ð82CB1136Ł[

The pentacoordinate aluminum derivative "016# is reported to be formed by reaction of lithiumbis"TMS#methanide with AlCl2[ Compound "016# rapidly underwent metalÐhalogen cleavage withAlCl2 in benzene yielding the salt!like adduct "017# "Scheme 36# ð76AG"E#570Ł[


N

M M

NTMS

TMS

TMS

TMS

(121) M = Cu(122) M = Ag

i, ii

THF, 20 °C

N

Li Li

NTMS

TMS

TMS

TMS

(93)

i, BuLi, ether, 1 h at 20 °C; ii, CuCl, THF, 1 h, 20 °C or AgBF4, THF, –78 °CScheme 44

Scheme 45

Sn N

TMS

TMS

(TMS)2N

Sn N

TMS

ClSn N

TMS

TMS

N

TMS

TMS

TMS

(123) (124)

(125)

(93)

2Sn[N(TMS)2]2 ether SnCl2, THF

or ether

2SnCl2ether

Sn NN

TMS

TMS

(126)

RN3

hexane, RT

~TMS

N

TMS

TMS

Sn Nr(124)

R

TMS2

R = 2,6 Pri2C6H3, 68%, 2,4,6-Me3C6H2, 79%

Scheme 46

AlN

N

TMS

TMS

TMS

TMS

AlN

NN

TMS

LiTMS

Cl

+

(128)

TMS TMS

Scheme 47

AlCl4–AlCl3

ether, 20 °C54%

AlCl3

benzene, 20 °C83%

(127)

TMSTMS

E}orts to generate a carbanionic species by the reaction of Al"CH"TMS#1#2 with t!butyllithiumin the presence of TMEDA have led to 0!sila!2!alanatetane "018#[ The reaction probably involvesan attack of the strong base to the bis"TMS#methyl substituent followed by intramolecular additionof a carbanionic center to the coordinatively unsaturated aluminum atom "Equation "29##ð78ZAAC"468#64\ 82CB1526Ł[ In contrast to Al"CH"TMS#1#2\ a sterically less crowded compound "029#reacts with t!butyllithium in the presence of N\N?!dimethylpiperazine "DMP# to give lithium "m!hydrido#trialkylalanate "020# "Equation "20## ð80ZAAC"484#114Ł[


ButLi/TMEDA


Al TMS

TMS

TMS

TMS

TMS TMS

Al SiMe

Me

TMS

TMS

TMS

TMS

TMS

–

Li(TMEDA)+

(129)

(30)

But Al

TMS

TMS

TMS

TMS

(131)

Al But

TMS TMS

TMS TMS

N

N

Me

Me

(31)

(130)

HButLi/DMP


A rare example of the double transmetallation reaction is shown in Equation "21#[ Bis"bro!momagnesio#TMS!methane reacts with chlorotrimethylstannane in THF to form bis"tri!methylstannyl#TMS!methane "021# in almost quantitative yield ð75TL5012Ł[

2Me3SnCl

THF, 20 °C94%

TMS SnMe3

SnMe3

TMS MgBr

MgBr

(132)

(32)

5[95[1[1[1 Functions bearing boron"s# and metal"s#

The chemistry and preparation of lithium poly"boryl#methides derived from methanetriboronicesters were reviewed in 0864 ð64S036Ł[ Since the late 0879s\ reviews containing information on thepreparation of boron!stabilized carbanions "borylmethide salts# have also appeared ðB!76MI 595!91\B!77MI 595!90\ 80COS"0#376Ł[ The present section considers the preparation of polyheteroatom speciesof the general formula RC"BX1#n"MLm#2−n\ where n�0 or 1\ M is metal\ and R�H\ alkyl\ or aryl[No methods exist which can be used to prepare all these types of compounds but there are syntheticroutes which have some generality[

"i# Synthesis via metalÐhydro`en exchan`e

Alkyllithium reagents and other strong bases can abstract a proton from carbon adjacent to aboryl group generating the metallated borylmethane[ In principle\ the reaction could provide ageneral method of synthesis\ but in certain cases highly nucleophilic bases react predominantly atthe boron atom leading to formation of {{ate|| complexes "Scheme 37# ð54TL2318\ 55TL3204\ 62S26Ł[Successful metalÐhydrogen exchange may be achieved in several ways as follows]

"a# the reagent can be a hindered\ nonnucleophilic base^"b# the groups around boron can be highly branched so that attack on boron is inhibited on steric

grounds^ or"c# the electrophilicity of the boron atom may be lowered by the use of heteroatom substituents

ð80COS"0#376Ł[

R2M

–R2H

R2M

R1

Y BX2

Y BX2

MR1

R1

Y B(R2)X2–

M+

Scheme 48


The example provided in Scheme 38 illustrates the generation of potassium bis"boryl#methanide"023# from sterically overcrowded bis"dimesitylboryl#methane ð71JCR"S#021Ł[ Interestingly\ while thereaction of structure "022# with lithium dicyclohexylamide gives lithium dimesitylborylmethide\Mes1BCH1Li\ in preparatively useful yield\ n!butyllithium attacks at boron to give the borate andt!butyllithium gives the hydroborate by b!hydrogen transfer ð72TL512Ł[

i, (c-C6H11)2NLiii, Mes2BF

THF, 20 °C Mes2B BMes2

K

(134)

KH

THFMes2B BMes2

Mes2BMe

(133)

Scheme 49

The deprotonation of bis"dialkoxyboryl#methanes has been accomplished with lithium 1\1\5\5!tetramethylpiperidine "LITMP# in the presence of TMEDA in THF "Equation "22## ð71OM19Ł[However\ the reaction is not completely general[ Thus\ the compound "025# undergoes cleavageinstead of deprotonation to give lithiated monoborylmethane "026# "Equation "23## ð71OM19Ł[

OB

OO

O

BO

BOO

O

BO

BO

BO

XO

=

, , , ,

LITMP/TMEDA

THF, –78 °CB B

O X

OO

X O

Li

B B

O X

OO

X O

(135)

(33)

LITMP/TMEDA

THF, –78 °CLi B

Ph

O

OB B

Ph

O

OO

O

(136) (137)

(34)

Diborylmethide salts can be alkylated by alkyl halides to form 0\0!bis"dialkoxyboryl#alkanes\which in turn can be deprotonated and alkylated with a second alkyl halide to form `em!diboronicesters\ R0R1C"B"OAlk1##1 ð71OM19Ł[

"ii# Synthesis via transmetallation reactions

A transmetallation reaction\ for the purposes of this section\ can be de_ned as a reaction in whicha borylalkyl group is transferred from boron to a metal atom by the reaction of an organometalliccompound with a suitable polyborylated methane[ The method is widely used for the preparationof lithium tris! and bis"boryl#methides starting from the corresponding polyborylated methanesand organolithium reagents "Equations "24# and "25## ð62JA4985\ 63JOM"58#34\ 64JA4597\ 65JOM"009#14\65JOM"003#0Ł[ In a typical procedure\ the tris"dialkoxyboryl#methane and methyllithium are stirredat −67>C in a polar solvent "normally THF or a mixture of THF and dichloromethane#[ Thereaction time appears to be substrate!dependent\ but the reaction is generally complete after about1[4 h at −67>C[ A borylmethide salt can be isolated or used in situ for subsequent derivatization[It should be noted that compounds such as "024# and "027# are very interesting as reagents forconversion of a carbonyl compound to the homologous aldehyde ðB!66MI 595!91\ 67JOC849\ 79JOC0980Ł[

MeLi

THF, –70 °C B B

O X

OO

X O

Li

B B

O X

OO

X O (135)

BO

XO

OB

O O

O

BO

BO

BO

XO

=

(35)

, ,


BunLi

THFB

B

B

B

O

O

O

O

O

O

O

O

B

B

B

Li

O

OO

O

O

O

(138)

(36)

The reaction of lithium bis"dialkoxyboryl#methides with organoelement halides\ such as Ph2MCl"M�Ge\ Sn\ or Pb#\ provides a general route to bis"boryl#"germyl#methanes and their tin and leadanalogues "Equation "26## ð65JOM"009#14Ł[ A further extension of this type of chemistry was thesuccessful conversion of the tin compound "028# to the methide salt "039# stabilized by one boronand one tin atom\ and _nally to bis"triphenylstannyl#ethylenedioxyborylmethane "030# "Scheme 49#ð65JOM"009#14Ł[ Tris"dialkoxyboryl#methide salts react with Ph2MCl in a similar fashion to formcompound Ph2MC"B"OAlk#1#2 ð58JA5430\ 62JOM"46#114\ 62JOM"46#120\ 63JOM"58#52Ł[

Ph3MCl

THF/ether36–77%

B B

O X

OO

X O

MPh3

B B

O X

OO

X O

Li

O

O

BO

BO

BO

XO

= or

M = Ge, Sn, or Pb

(37)

MeLi

THF, –78 °CB B

SnPh3

O

OO

O

B Li

SnPh3

O

O

B SnPh3

SnPh3

O

O

Ph3SnCl

47%

(139) (140) (141)

Scheme 50

Treatment of tetrakis"dimethoxyboryl#methane with butyllithium or\ preferably\ lithium methox!ide\ followed by triphenyltin chloride yields tris"boryl#stannylmethane "031#\ which on furthertreatment with butyllithium disproportionates to form bis"boryl#bis"stannyl#methane "032# "Scheme40#[ Reaction of the monotin compound "031# with ethylene glycol resulted in the loss of one of thethree boron atoms to give "triphenylstannyl#bis"ethylenedioxyboryl#methane "028# "Equation "27##[The tin compound "032# undergoes similar reaction on treatment with lithium methoxide in meth!anol\ providing an alternative route to "boryl#bis"stannyl#!substituted methanes "Equation "28##ð62JOM"46#114Ł[

MeOLi or BunLi

THF, 20 °C

Ph3SnCl

65%(MeO)2B B(OMe)2

B(OMe)2(MeO)2B

(MeO)2B B(OMe)2

Li(MeO)2B

BunLi

THF, –78 °C93%

(MeO)2B B(OMe)2

SnPh3(MeO)2B

(MeO)2B B(OMe)2

SnPh3Ph3Sn

(142) (143)

Scheme 51

1/2

HO(CH2)2OH

acetone, 20 °C90%

B B

SnPh3

O

OO

O(139)

(142) (38)


MeOLi

MeOH, reflux57%

Ph3Sn B(OMe)2

SnPh3

(143) (39)

The reaction of benzylbis"boryl#methane "033# with mercuric dichloride and lithium methoxidein anhydrous methanol resulted in the selective replacement of one boron atom by mercury to formthe a!metallated borylmethane "034# "Equation "39## ð65JOM"003#0Ł[ Interaction of boryl"stannyl#!alkanes with alkyllithiums generally leads to cleavage of the tin moiety "Equation "30## ð74OM0589Ł[A useful reaction of dimesitylboryl"TMS#alkanes is that they readily undergo silicon:lithium ex!change with LiF to form lithium borylmethides ð80COS"0#376Ł[

HgCl2/NaOMe

MeOH, 25 °C77%

B B

CH2Ph

O

OO

O(144)

ClHg B

CH2Ph

O

O

(145)

(40)

MeLi

THF, –100 °C

Me3Sn B

O

OLi B

O

O(41)

"iii# Synthesis via addition to vinylboranes and methyleneboranes

The very low yields of lithium borylmethide salts "ca[ 4)# obtained from the reactions ofalkenyldimesitylboranes with organometallic compounds demonstrates that this is not a very usefulmethod for the synthesis of simple a!metallated borylmethanes[ However\ this approach has provedsuccessful for the preparation of a!metallated silyl"boryl#methanes from 0!TMS!0!dimesityl!borylethylenes "see Section 5[95[1[1[3# and several alkali metal polyborylmethides from methylene!boranes ð80COS"0#376Ł[

A speci_c reaction useful for the synthesis of diboriranide "035#\ is shown in Scheme 41[ Treatmentof "035# with the very weak acid t!butyl"TMS#amine leads to formation of "036# ð74AG"E#677Ł[

K/Na

THF, 82%

R1R2NH

>90%

B

B

R2

Cl

R2

ClR1

R1

K

R1

R2

K

BB

R2

R2

R2

R1

K

BB

R2

R2

(146) (147)

R1 = TMS, R2 = But

Scheme 52

C!Borylborataalkyne "037# with t!butyllithium yields 0\2!diborataallene "038#\ which containsa second t!butyl group in place of the "TMS#1CH group[ Upon treatment with one equiv[ ofcyclopentadiene\ the 0\2!diborataallene is transformed into the lithium bis"boryl#methide "049#"Scheme 42# ð77AG"E#0269Ł[ Several cyclic compounds\ such as "040# and "041#\ incorporating aC"Li#B1 unit\ have been made by a related 0\1!addition of the C0Li bond to the B1C multiplebond "Equations "31# and "32## ð89AG"E#0929\ 81AG"E#0127Ł[ Readers are referred to a review byBerndt ð82AG"E#874Ł for more detailed information concerning the synthetic potential of meth!yleneboranes in carbometallation reactions[

ButLi

50%B • B

But

MesMes

But

Li

B BBut

Mes

But

Mes

CpHB • B

Mes

TMSTMS

Mes

(148) (149) (150)

Scheme 53

2Li+–

– –


PhLiBB TMS

TMS

Ar

Ar

BTMS

TMSB

Li

ArPh

Ar(151)

Ar = 2,3,5,6-Me4C6H (Dur)

(42)

(152)

ButLi

20%B

B

TMS

TMS

Ar

BAr

Ar

B

B

TMS

TMS

Ar

Ar

BBut

Li

Ar

Ar = Dur, Mes

(43)

A unique reaction leading to the formation of a C"Sn#B1 function has been described by Berndtand co!workers ð76AG"E#435Ł[ The boranediylborirane "042# which\ according to calculations\ hasthe nonclassical structure shown in Scheme 43\ behaves toward suitable reagents as if it were thecarbene[ Reaction of "042# with a stannylene in pentane led to formation of the stannaethene "043#in quantitative yield[ Compound "043# reacts with HCl to give the 0\2!diboretane "044#[

BBTMS

TMS

R

R B

B

TMS

TMS

R

R

(154)

HCl

~100%

Sn[CH(TMS)2]2

pentane, 20 °C

:

B

B

TMS

TMS

R

Sn

R

B

B

R

R

TMS

TMSCH(TMS)2

CH(TMS)2

Sn

(153)

(155)

TMS

TMS

Cl

R = But

Scheme 54

5[95[1[1[2 Functions bearing germanium"s# and metal"s#

Isolable examples of compounds of the type RC"GeX2#n"MLm#2−n "n�0 or 1# are virtuallyunknown[ The signi_cant contribution to this class of compounds was made by Barton andHockman who reported the preparation and synthetic utilization of lithium bis"tri!methylgermyl#methide "045# ð79JA0473Ł[ This reagent is formed in good yield by methods similarto those described for the analogous silicon compound "Scheme 44#[ The synthetic utility of "045#has been demonstrated by the reaction with tosyl azide leading to the formation ofbis"trimethylgermyl#diazomethane[

The triphenylgermyl group seems to have no acidifying e}ect^ lithiation of "Ph2Ge#1CH1 was

Me3Ge Cl Me3Ge GeMe3

Me3Ge GeMe3

Li

Me3Ge GeMe3

Cl

i, ii

iv

v

iii

(156)

i, Li, ether, –23 °C; ii, Me3GeCl; iii, ButLi, THF/HMPA, –78 °C; iv, BusLi, THF, –78 °C; v, Li, etherScheme 55


neither possible with lithium dicyclohexylamide nor with n!butyllithium or t!butyllithium in thepresence of HMPA ð79TCC"81#098Ł[

Treatment of "Ph2Pb#1CHLi with Ph2GeCl produced the germylbis"stannyl#methane "046#\ whichwas converted into functionalized lithium methide "047# by a transmetallation reaction with phe!nyllithium "Equations "33# and "34## ð79TL1796Ł[

Ph3Pb PbPh3

GePh3(Ph3Pb)2CHLi

THF, 87%

(157)

Ph3GeBr (44)

Ph3Pb Li

GePh3PhLi

>78%

(158)Ph3Pb PbPh3

GePh3(45)

5[95[1[1[3 Functions with mixed metalloid"s# and metal"s#

Only a few totally mixed RC"E0Xn#"E1Ym#MLk molecules "E0 and E1�Si\ Ge\ or B^ M�metal#have been described[ If unsymmetrical compounds such as XnE0CH1E1Ym or XnE0CH"Hal#E1Ym

are available\ then metalÐhydrogen or metalÐhalogen exchange reactions seem to be the mostpractical routes to metallated derivatives[ Redistribution represents a potential problem and can beavoided by mild reaction conditions and rapid experimental work up procedures[

Several metallating reagents have been examined\ but the most satisfactory method for metallationof TMS"ethylenedioxyboryl#methane "048# involves the use of LITMP:TMEDA in THF "Scheme45# ð79CC28\ 72OM129Ł[ In contrast to "048#\ substituted TMS"ethylenedioxyboryl#methanes\TMSCH"R#BO1C1Me3 "R�alkyl\ aryl# have proved resistant to the usual deprotonation conditionsð79JOM"073#C30Ł[

LITMP/TMEDA

THF, 0 °C

TMS B

O

OTMS B

O

O

Li

(159)

RHa1

53–85%

TMS B

O

O

R

R = Bu, Am, Hex, PhCH2, PhCH2CH2, PhOCH2CH2

Scheme 56

Lithiation of TMS"trimethylgermyl#methane may be accomplished with t!butyllithium in a mix!ture THF:HMPA at −67>C[ A successful alternative method utilizes the chloro derivative "Scheme46# ð79JA0473Ł[

TMS GeMe3

Li

ButLi

THF/HMPA, –78 °C

Li

ether, reflux

TMS GeMe3

TMS GeMe3

Cl

Scheme 57

A versatile approach to metallated polyheteroatom!substituted methanes based on the reactionsof tris"triphenylplumbyl#methane has been developed by Kau}mann and co!workers ð79TCC098\79TL1796Ł[ Germyl"plumbyl#methide "047# undergoes coupling reactions with TMS!Cl to yield thefunctionalized methane "059# "Equation "35##[ Transmetallation of silylbis"plumbyl#methanes "051#with PhLi gives a new organolithium reagent as shown in Scheme 47 ð79TL1796Ł[ The required


lithium bis"plumbyl#methide "050# can be obtained by a transmetallation reaction of "Ph2Pb#2CHwith PhLi ð79TL1796Ł[

Ph3Pb GePh3

TMSTMS-Cl

78%

(160)(158)Ph3Pb GePh3

Li(46)

Ph3Pb PbPh3

TMSTMS-Cl

89%

(162)(161)

Ph3Pb PbPh3

Li

Ph3Pb Li

TMSPhLi

>70%

Scheme 58

5[95[2 FUNCTIONS CONTAINING THREE METALS

5[95[2[0 Three Similar Metals

Isolable compounds of the type RC"MLm#2 "M�metal# are known with M�Li\ Hg\ Al\ Sn\ andPb[ Methods of synthesizing polylithiated aliphatic hydrocarbons have been reviewed previouslyðB!74MI 595!91\ 76TCC0Ł[ The chemistry and preparation of acyclic compounds with functionscontaining three heavy main group metals have not been surveyed and only passing comments canbe found in appropriate sections of Methoden der Or`anischen Chemie ð69HOU"02:3#0\ 63HOU"02:1b#0\67HOU"02:5#070Ł\ Comprehensive Or`anometallic Chemistry ð71COMC!I"6#154Ł and in several spe!cialized books ð53AOC"1#146\ 79TCC"81#098\ B!70MI 595!91\ B!76MI 595!90Ł[

5[95[2[0[0 Lithium derivatives\ RCLi2

Polylithium organic compounds can be prepared by a variety of methods and several have beenextensively studied ð76TCC"027#0\ 81MI 595!91Ł[ However\ only a few of these methods are readilyapplicable to the preparation of geminal trilithioalkanes with at least some degree of generality[These are]

"a# reactions of hydrocarbons or halocarbons with lithium vapor^"b# transmetallation reactions^"c# metallation of acidic hydrocarbons^ and"d# pyrolysis reactions[When applicable\ transmetallation\ especially mercuryÐlithium exchange\ is usually the most

convenient and is therefore the method of choice[ On the other hand\ reactions of hydrocarbon orhalocarbon substrates with lithium vapor probably represent the most general approach[ CarbonÐlithium bonds in polylithiated alkanes are very susceptible to hydrolysis and the handling of anysuch compound requires the use of vacuum systems and other specialized techniques[

"i# Reactions with lithium vapor

Direct halogenÐmetal exchange in polyhaloalkanes by treatment with lithium metal\ the mostpopular method for the synthesis of alkyllithium compounds\ is only of limited value for thepreparation of polylithiated alkanes due to a!elimination of lithium halide after the _rst step beingfaster than the halogenÐmetal exchange ð68AG"E#674\ 79HCA1935Ł[ These di.culties can be overcomeby high!temperature reaction of polyhaloalkanes with lithium vapor[

Thus\ tetralithiomethane\ CLi3\ and hexalithiomethane\ C1Li5\ the _rst examples of perlithiatedalkanes\ were prepared by the reaction of lithium vapor with the appropriate perchlorocarbonsunder vacuum at high temperatures "649Ð0999>C# ð61CC0967\ 72JOM"138#0Ł[ The reactions are carriedout in a stainless steel reactor consisting of a Knudsen cell containing lithium metal heated in afurnace\ an inlet tube\ and a liquid nitrogen cold _nger[ The main advantage of this technique\besides the high reactivity of lithium vapor\ is the reduction of rearrangements and secondary

194Three Metals

reactions from rapid quenching of the products onto the cold _nger ð76TCC0Ł[ In both prep!arations\ depicted in Equations "36# and "37#\ the main by!products were C1Li3 and C1Li1[ Furtherinvestigations showed that the selectivity can be improved by working at 649>C instead of 749>Cð64CC291\ 68JOC1200\ 71JA6234Ł[ However\ the method although optimized\ still provides a maximumof 39) CLi3 together with 47) C1Li1 ð72JOM"138#0Ł[ When chloroform was used as a substrate\trilithiomethane was obtained in 04[4) yield "Equation "38##^ the main side products being 28[6)C1Li1\ 19[0) CLi3\ and 08[0) CH1Li1 ð71JA6234\ 72JOM"138#0Ł[ Similarly\ the reaction of dich!loro"TMS#methane with lithium vapor gave TMS!CHLi1 in only 00) yield "Equation "49##ð73CC0553Ł[

850 °CCCl4 + 8Li(g) CLi4 + 4LiCl (47)

850 °CC2Cl6 + 12Li(g) C2Li6 + 6LiCl (48)

750 °CCHCl3 + 6Li(g) CHLi3 + 3LiCl (49)

720 °CTMS-CHCl2 + 4Li(g) TMS-CHLi2 + 2LiCl (50)

The purest perlithiated ethane "C1Li5# was prepared by using diethylmercury instead of hexa!chloroethane as the starting material ð68JA1103Ł[ It was also reported that the vapor phase reactionof carbon with atomic lithium yielded perlithiopropyne "C2Li3# as the main product ð62JA0232Ł[

The major drawback of a technique utilizing reactions between organic substrates and lithiumvapor lies in the separation of a mixture of lithium!substituted hydrocarbons[ Unfortunately\ it hasnot yet been possible to separate the resulting mixtures\ and even separation from the lithium matrixis di.cult ð72JOM"138#0\ 81AG"E#473Ł[

"ii# Transmetallation reactions

In many cases of synthesis of substantial amounts of pure polylithiated alkanes there is nopractical alternative to transmetallation reactions ð76TCC"027#0Ł[ However\ since the transmetallationroute requires the intermediacy of another organometallic compound\ polylithiated alkanes pre!pared by this method share the same limitations and restrictions that the parent organometalliccompound encounters[ In practice\ mercuryÐlithium exchange reactions represent one of the moste}ective routes to the di! and trilithiomethanes because the corresponding organopolymercurycompounds are comparatively readily available[ Thus\ trilithiomethane "HCLi2# can be prepared ingood yield by treating tris"chloromercurio#methane with lithium metal in dry THF "Equation "40##ð71MI 595!90Ł[ Unfortunately\ direct mercuryÐlithium exchange reaction is not suitable for thesynthesis of tetralithiomethane "CLi3#[ Treating C"HgCl#3 with lithium metal in diethyl ether resultedin the dimeric products hexalithioethane "C1Li5# and tetralithioethylene "C1Li3#[ The reaction isbelieved to proceed via radical intermediates ð76TCC"027#0Ł[

Li Li

LiLi

THF, 20 °CClHg HgCl

HgCl(51)

A variant of the mercuryÐlithium exchange method is provided by the reaction of organomercurycompounds with n!butyllithium[ Many of the polymercury compounds\ including C"HgCl#3ð73AG"E#884\ 75OS267Ł and CH1"HgCl#1 ð72AG"E#622Ł\ are useful in this reaction[ However\ the pro!cedure has not yet been adequately developed for synthesis of trilithiated hydrocarbons[

Transmetallation reactions with several other elements\ such as boron and tin\ can also be usedfor the generation of polylithiated organic compounds ð79TCC"81#098\ 71AG"E#309Ł but trilithiatedhydrocarbons have not yet been prepared this way[

"iii# Metallation of acidic hydrocarbons

Much more easily accessible than the 0\0\0!trilithiated alkanes are certain perlithioalkynes\ sincealkyllithium reagents can abstract quantitatively not only the hydrogen atoms on sp!hybridized


carbon atom\ but also those of the adjacent methyl group ð63MI 595!90\ 71AG"E#309\ 72T1622Ł[ Forexample\ the conversion of propyne into perlithiated derivative can be achieved by reaction with n!butyllithium in hexane "Equation "41## ð54JA2677\ 58JA5045\ 73AG"E#884Ł[

BunLi

hexane, 75%C3Li4 (52)

The pattern of reactivity of conjugated diynes closely resembles that of the propyne[ Thus\reaction of the 0\2!pentadiyne with excess n!butyllithium:TMEDA in hexane gives the perlithiatedhydrocarbon C4Li3 "Equation "42## ð62JA2213Ł[ 1\3!Hexadiyne under the same conditions ð65JA7315Łor even in the absence of TMEDA ð62JCS"P1#488Ł has been converted into the trilithiated product"Equation "43##[ Metallation of 1\3!octadiyne in diethyl ether or THF a}ords another {{lithiocarbon||"Equation "44## ð62JCS"P1#488Ł[

BunLi

hexaneC5Li4 (53)

BunLi

hexaneMeC5Li3 (54)

C3H7C5Li3 (55)BunLi

ether or THFC3H7

Unlike alkynes\ linear and branched alkenes upon treatment with organolithium reagents formonly mono! and dilithiated hydrocarbons[ For example\ propene is dilithiated with n!butyl!lithium:TMEDA in hexane to give the corresponding dianion ð64CC766Ł[ Isobutylene under theseconditions yields the cross!conjugated trimethylenemethane dianion ð65T0728Ł[ The isomeric 1!butene can be dilithiated to give 0\3!dilithio!1!butene ð63JA4539Ł[

"iv# Pyrolysis reactions

The pioneering work in this _eld is due to Ziegler et al[ who reported that pyrolysis of halide!free methyllithium resulted in the formation of dilithiomethane in excellent yield "Equation "45##ð44ZAAC"171#234Ł[ This procedure is still the method of choice for the preparation of CH1Li1\however\ it is not the best route to 0\0\0!trilithiated hydrocarbons[ Although perlithiopropyne"C2Li3# was detected among the products of the thermal decomposition of CH1Li1 and CLi3 "Equa!tions "46# and "47##\ it could not be separated from the resulting mixtures ð70JA4840\ 71JA1526\74JA4202Ł[

225 °CMeLi CH4 + CH2Li2 (56)

350 °C

6 minCH2Li2 C3Li4 + C2Li2

20% 80%

(57)

225 °C

8 minCLi4 CLi4 + C3Li4

20% 40%

+ C2Li4 + C2Li230% 10%

(58)

5[95[2[0[1 Mercury derivatives\ RC"HgX#2

As in many other cases\ transmetallation represents a valuable route to polymercurated methanes[Thus\ tris"dimethoxyboryl#methane\ readily available via the reaction of chloroform with di!methoxyboron chloride and lithium metal "see Section 5[95[1[0[1#\ undergoes a rapid reaction withmercuric salts to produce trimercurated methanes "Equation "48## ð79JOM"080#6\ 72JOM"132#134Ł[

196Three Metals

XHg HgX

HgXHgX2

THF, RT(MeO)2B B(OMe)2

B(OMe)2

X = Cl, 62%; AcO, 38%

(59)

However\ despite the usefulness of transmetallation reactions\ this route to trimercurated deriva!tives has rarely been used\ because access is easier via direct mercuration of organic compoundscontaining an activated methyl group ðB!56MI 595!90\ 57MI 595!90\ 60MI 595!90\ 63HOU"02:1b#0\ B!70MI 595!91Ł[ Treatment of methyl derivatives containing electron!withdrawing groups with a mercuric salt\HgX1\ results in electrophilic mercuration giving a mercury derivative[ Use of an excess of HgX1

may give rise to trimercurated compounds[ Typical examples from the literature are given in Table3[ The reactions are normally carried out in aqueous acidic solutions or without solvent at elevatedtemperatures[ For example\ acetonitrile reacts with anhydrous mercuric acetate at 049>C for 19 hin a bomb tube to give the trimercurated product in 82) yield "Table 3\ entry 7#[ Conditionsfor preparing the mono! and dimercurated derivatives of acetonitrile have also been describedð63JPR446Ł[

Table 3 Preparation of 0\0\0!trimercurioalkane derivatives[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

YieldEntry Compound Method of preparation ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ0 HC"HgCl#2 HCðB"OMe#1Ł2¦HgCl1 51 79JOM"080#61 HC"HgBr#2 HCðB"OMe#1Ł2¦HgBr1 72JOM"132#1342 HC"HgI#2 HC"HgOAc#2¦KI 71 72JOM"132#1343 HC"HgOAc#2 HCðB"OMe#1Ł2¦Hg"OAc#1 27 72JOM"132#1344 HC"HgSCN#2 HC"HgOAc#2¦KSCN 72JOM"145#1065 HC"HgCN#2 HC"HgOAc#2¦KCN 72 72JOM"132#1346 HC"HgMe#2 HCðB"OMe#1Ł2¦MeHgOAc 75JOM"290#07 NCC"HgOAc#2 MeCN¦Hg"OAc#1 82 63JPR4468 NCC"HgMe#2 MeCN¦"MeHg#1O 84 64ZAAC"304#122

09 OHCC"HgCl#2 EtOH¦HgCl1:NaOAc 71JOM"127#21600 OHCC"HgBr#2 EtOH¦HgBr1:NaOAc 71JOM"127#21601 OHCC"HgBr#2 AcH¦Hg"NO2#1 76JOM"208#002a HO1CC"HgCl#2 {mercuretin|¦HCl 84 73JOM"165#003a HO1CC"HgOAc#2 {mercuretin|¦AcOH 43 73JOM"165#004a HO1CC"HgNO2#2 {mercuretin|¦HNO2 75JOM"295#0*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐa{{Mercuretin||] AcOðHgC"HgOAc#1CO1ŁnH "n½9#[

Mercuration of C0H bonds a to carbonyl groups also occurs readily[ Thus\ reaction of aceticaldehyde with HgCl1 led to the formation of "ClHg#2CCHO in almost quantitative yield[ Mer!curation of the aldehyde RCH1CHO "R�Me\ Et# gave "ClCH1#1CRCHO "74Ð77)# ð73CCA578Ł[The product obtained by boiling an ethanolic solution of mercuric chloride with sodium acetateð0788CB769Ł has also been identi_ed as tris"chloromercurio#acetaldehyde "Table 3\ entry 09#[ Thebromine analogue was obtained in the same way ð71JOM"127#216Ł[ The crystal structures of solvates"ClHg#2CCHO=DMF and "BrHg#2CCHO=DMSO have been determined by x!ray di}ractionmethods ð71CSC0460\ 71JOM"127#216Ł[

Mercuration of acetaldehyde with mercuric nitrate in aqueous nitric acid always leads to tri!mercurated acetaldehyde\ which separates from the solution in the form of various nitrates whosetype and composition depends upon the acid concentration ð76JOM"208#0Ł[ Addition of an ethanolicsolution of acetaldehyde to an aqueous solution of mercuric nitrate gives a hydrated oxoniumnitrate of tris"mercurio#acetaldehyde\ "OHg2CCHO#NO2=H1O ð72JOM"142#172Ł[

It has been con_rmed that the compounds obtained by melting mercuric acetate\ named mer!curetin ð16JCS1547Ł\ is identical with the compound prepared by heating mercuric acetate in aceticanhydride ð92LA"218#005Ł[ Mercuretin\ prepared by both routes\ has been identi_ed as the con!densation polymer of tris"acetoxymercurio#acetic acid\ AcO"HgC"HgOAc#1CO1#nH\ with n approxi!mately equal to 09[ Its hydrolysis in dilute HCl gives tris"chloromercurio#acetic acid as the only Hg!containing product "Table 3\ entry 02#[ Two nitrates of trimercurated acetic acid\ obtained fromthe solution of mercuretin in nitric acid were identi_ed as ð"Hg"H1OHg#"NO2Hg#CCO1#NO2Ł and"1"NO2Hg#2CCO1H=HNO2# ð75JOM"295#0\ 80JOM"300#08Ł[

The reaction of 1!ethyl! and 1\3\3\4\4!pentamethyl!0\2!dioxalanium perchlorate with Hg"OAc#1and Hg"OCOCF2#1 leads to the formation of mono!\ di!\ and trimercurated carboxylic acids depend!


ing upon the ratio of reagents ð70ZOB1130Ł[ Mercuration of acetone in acidic aqueous solutionsproduces at least nine mono!\ poly!\ and permercurated species\ all of which can exist in equilibriumsimultaneously ð78OM1535Ł[

5[95[2[0[2 Aluminum derivatives\ RC"AlX1#2

Geminal trialuminioalkanes are available via bishydroalumination of alkynyldialkylalanesð69HOU"02:3#0Ł[ In general\ the reaction of terminal alkynes with two molar equiv[ of a dialkyl!aluminum hydride in ether or THF lead to 0\0!dialuminioalkanes "Equation "59## ð59LA"518#111\55TL5910\ 60CC0482Ł[ However\ in basic solvents such as triethylamine\ the reaction of alkynes withone molar equiv[ of dialkylaluminum hydride produces metallation rather than hydroaluminationð52AG"E#575\ 57IZV809Ł[ This has been used synthetically to prepare alkynylalanes[ Further treatmentof the resultant alkynylalanes with excess dialkylaluminum hydride a}ords trialuminioalkanes "052#"Scheme 48# ð59LA"518#111\ 52BSF0351Ł[

R22Al AlR2

2

2R22AlH

ether or THF(60)R1

R1

R1 = Bun, R2 = EtScheme 59

R22Al AlR2

2

2R22AlH

70 °C

AlR222R2

2AlH

Et3N, 20 °CR1

(163)

2R22AlH

70 °CAlR2

2R1

R1

Related preparation of 0\0\0!trialuminioalkanes involves bishydroalumination of alkynylalanesderived from the reaction of alkali metal acetylides with dialkylaluminum chlorides "Scheme 59#ð59LA"518#111\ 57BSF105Ł[

R = Me, Et

Scheme 60

R2Al AlR2

AlR2R2R22AlH

NaR2AlCl

80–90%R AlR2R

The chemistry of 0\0\0!trialuminioalkanes is not well developed\ and only the reactions of com!pound "052# with electron!donor molecules\ such as LiH\ KF\ Et1O\ and pyridine have been reportedð72IZV525Ł[

5[95[2[0[3 Tin and lead derivatives\ RC"MX2#2 "M�Sn or Pb#

Tris"trimethylstannyl#methane "053# can be readily synthesized via interaction of chloroform withtrimethylstannyllithium ð64OMS"09#07Ł or via reaction of bromoform with the Grignard reagentobtained from chlorotrimethylstannane and magnesium turning "Scheme 50# ð73JOM"155#26Ł[ Bothprocedures give the crude product containing substantial quantities of bis"trimethylstannyl#methane[Distillation and subsequent crystallization from ethanol a}ord a pure substance in average yield[

Me3Sn SnMe3

SnMe3

Me3SnLi

THF, 20 °CCl Cl

Br Br

Br Me3SnCl/Mg

THF

Cl

Scheme 61

(164)

198Three Metals

A more general route to 0\0\0!tristannylalkanes involves the hydrostannation of 0!stannyl!0!alkynes[ Trimethyltin hydride has been shown to react with 0!stannyl!0!alkynes in the presence ofcatalytic amounts of azobisisobutyronitrile "AIBN# to form predominantly 0\0!distannyl!0!alkenes"054#[ The latter undergo a second hydrostannation to give the corresponding 0\0\0!tristannylalkanes"Scheme 51# ð72JOM"141#36\ 74OM0933Ł[

Me3SnH

70 °C, AlBN8 h

SnMe3R

SnMe3

SnMe3

R SnMe3R

Me3Sn+

(165) (166)

Me3Sn SnMe3

SnMe3RMe3SnH

52–80%(165)

R(ratio (165)/(166), %): Me (97/3), Bun (96/4), But (98/2), Ph (95/5), MeOCH2 (59/41), PhOCH2 (61/39), PhO

R = Me, Bun, Ph, PhCH2, MeOCH2, PhOCH2, PhO

Scheme 62

0\0!Distannyl!1\1!diorganyl!0!alkenes\ resulting from the coupling reaction of geminal dibro!moalkenes with Me2SnLi\ have also been successfully transformed into the corresponding tri!stannylalkanes "Scheme 52# ð75OM0880Ł[

Me3SnLi

THF, –78 °C

SnMe3

SnMe3

R1

R2

Me3SnH

hν

Br

Br

R1

R2

R1 = Me, CH2OMe; R2 = Me, Et, Ph, CH2CH2OMe, CH(Me)OMe, CH2CH2OEt, CH2OMeScheme 63

SnMe3

SnMe3

R1

R2

SnMe3

Oxymetallation of the alkene derivative "056#\ which is achieved by using Me2SnOMe in hexane\yields functionalized tristannylalkanes "057# "Equation "50## ð80CB492Ł[ The reaction is believed toinvolve the formation of adduct at the boryl group followed by intramolecular rearrangements[

Me3SnOMe

hexane, 25 °C

SnMe3

SnMe3

B

R

SnMe3

SnMe3

R2B

R

R

MeO

R SnMe3

(167) (168)

(61)

R = Et

The preparative chemistry of triplumbylmethane derivatives is considerably less rich as comparedto the chemistry of tristannylmethanes[ The coupling reaction between chloroform and trior!ganylplumbyllithium is the sole valuable route to tris"triorganylplumbyl#methanes ð69JOM"12#360\74CB279\ 80SA"A#738Ł[ The method is especially e.cient for triphenylplumbyl derivatives since thePh2PbLi is readily available from Ph2PbCl and lithium metal "Equation "51## ð74CB279Ł[

Ph3Pb PbPh3

PbPh3HCCl3

THF, –60 °C91%

LiPh3PbCl Ph3PbLi (62)

The following compounds were made analogously^ "Ph2Pb#3C\ "Ph2Pb#1CCl1\ Ph2PbCHCl1\ and"Ph2Pb#1CH1[ Attempts to prepare "Ph2Pb#2CCl and "Ph2Pb#1CHCl failed\ because of further reac!tion with triphenylplumbyllithium ð69JOM"12#360Ł[

5[95[2[1 Three Dissimilar Metals

Trimetallated alkanes with di}erent metals attached to carbon are rare[ Even so\ access to thesespecies is of great interest because it is usually di.cult to reach such structures by classical routes[


A few of the compounds have been prepared by transmetallation or metallation reactions andexamples are described in reviews by Kau}mann ð79TCC098\ 71AG"E#309Ł[

The conversion of 0\0\0!tris"diethylaluminio#hexane "052# into lithiobis"diethylaluminio#hexanehas been achieved using reactions with n!butyllithium[ It was noted that only one diethylaluminiogroup can be replaced by lithium even when an excess lithium reagent was used "Scheme 52#ð72IZV525Ł[

Et2Al AlEt2

BunLi

C6H6, 20 °C

LiH11C5

Et2Al AlEt2

AlEt2H11C5

(163)

(63)

Compounds with the grouping Sn0C"Li#0Sn are accessible via the reaction of bis"tri!methylstannyl#methane with lithium dicyclohexylamide "LDCA# in presence of 0 mol HMPAð68TL490Ł[ The nature of the lithium reagent is critical^ generally\ deprotonation occurs with lithiumamides\ while transmetallation occurs with alkyllithiums ð79TCC098\ 89S148Ł[ An alternative methodfor the preparation of lithium bis"stannyl#methide "058# consists of treating a tristannylated com!pound with phenyllithium in ether "Scheme 53#[ Reaction of lithium derivative "058# with Ph2SnClgave tris"triphenylstannyl#methane ð79TCC"81#098Ł[

Ph3Sn SnPh3

Li

LDCA/HMPA

THF, 20 °CPh3Sn SnPh3

Ph3Sn SnPh3

SnPh3 PhLi

ether, 20 °C

Scheme 64

(169)

LDCA = lithium dicyclohexylamide

The lithium bis"triphenylplumbyl#methide "069# has been synthesized via several routes^ met!allation of bis"triphenylstannyl#methane\ transmetallation reaction using "Ph2Pb#2CH and phenyl!lithium\ or by halogenÐmetal exchange starting from bromobis"triphenylplumbyl#methaneð79TL1796Ł[ Lithium derivative "069# reacts smoothly with Me2SnCl to give the expected "stan!nyl#bis"plumbyl#methane "060# "Equation "53##[

Ph3Pb PbPh3

SnMe3Me3SnCl

THF, 88%Ph3Pb PbPh3

Li

(170) (171)

(64)

The synthetic potential of compounds of structures "058# and "069# in reactions with other metalhalides remains unexplored[


6.07Functions Containing FourHalogens or Three Halogensand One Other HeteroatomSubstituentALEX H. GOULIAEVAarhus University, Arhus, Denmark

and

ALEXANDER SENNINGTechnical University of Denmark, Lyngby, Denmark

5[96[0 TETRAHALOMETHANES*C"Hal#3 101

5[96[0[0 Four Similar Haloèns 1015[96[0[0[0 Tetra~uoromethane\ CF3 1015[96[0[0[1 Tetrachloromethane\ CCl3 1035[96[0[0[2 Tetrabromomethane\ CBr3 1045[96[0[0[3 Tetraiodomethane\ CI3 105

5[96[0[1 Three Similar and One Different Haloèn 1065[96[0[1[0 Tri~uoromethyl halides 1065[96[0[1[1 Trichloromethyl halides 1195[96[0[1[2 Tribromomethyl halides 1115[96[0[1[3 Triiodomethyl halides 112

5[96[0[2 Two Similar Haloèns 1125[96[0[2[0 Di~uoromethylene dihalides 1125[96[0[2[1 Dichloromethylene dihalides 1135[96[0[2[2 Dibromomethylene dihalides 1155[96[0[2[3 Diiodomethylene dihalides 116

5[96[0[3 Bromochloro~uoroiodomethane\ CBrClFI 117

5[96[1 METHANES BEARING THREE HALOGENS 117

5[96[1[0 Three Haloèns and a Chalcoèn 1175[96[1[0[0 Three haloèns and an oxyèn function 1175[96[1[0[1 Three haloèns and a sulfur function 1215[96[1[0[2 Three haloèns and an Se or Te function 126

5[96[1[1 Three Haloèns and a Group 04 Element 1265[96[1[1[0 Three haloèns and a nitroèn function 1265[96[1[1[1 Three haloèns and a phosphorus function 1315[96[1[1[2 Three haloèns and an As\ Sb\ or Bi function 132

5[96[1[2 Three Haloèns and a Metalloid 1325[96[1[2[0 Three haloèns and a silicon function 132

100

101 Four Haloèns or Three Haloèns and One Other Heteroatom

5[96[1[2[1 Three haloèns and a boron function 1325[96[1[2[2 Three haloèns and a èrmanium function 133

5[96[1[3 Three Haloèns and a Metal Function 133

5[96[0 TETRAHALOMETHANES*C"Hal#3

The _rst part of this chapter is con_ned to a limited number of compounds\ they are the24 possible tetrahalomethanes "Table 0# of which many are commercially available plus a fewtri~uoromethyl compounds of hypervalent iodine which have been prepared[ Most of the tetra!halomethanes have been prepared with the exception of the eight iodine!containing tetra!halomethanes\ CClI2\ CFI2\ CBrCl1I\ CBr1ClI\ CBr1I1\ CClFI1\ CBrClI1 and the chiral CBrClFI[Information on high yielding and selective syntheses of CBrI2\ CCl1I1 "formed as a by!product# andCBrFI1 "04) as a by!product# is\ however\ also rather sparse[

Organic per~uoro compounds have many practical applications\ such as in refrigerants\ aspropellants\ as _re extinguishers\ in the plastics industry as well as in the manufacture of phar!maceuticals\ whereas perchloro "apart from CCl3#\ perbromo and periodo compounds are more orless only of academic interest[

Methods for introducing ~uorine into organic compounds are presented elsewhere in this volumeand are not discussed in this chapter[ For more information there is a number of excellent bookson haloorganic compounds[ Organic ~uorine compounds have been treated by several authors[

The most recent handbook is Hudlicky|s Chemistry of Orànic Fluorine Compounds ðB!81MI596!90Ł[ This book covers all _elds of organic ~uorine chemistry\ including methods for introducing~uorine into organic compounds\ reactions\ properties\ analysis and practical applications of these\as well as synthetic procedures and the synthesis of ~uorinating agents[ Olah et al[ ðB!81MI 596!91Łhave published a book covering the synthesis of ~uorine compounds\ as have Liebman etal[ ðB!77MI 596!90Ł\ whereas German and Zemskov mainly cover reagents for the synthesis of~uorine compounds ðB!78MI 596!90Ł[ Older books include Chambers| Fluorine in Orànic ChemistryðB!62MI 596!90Ł\ Sheppard and Sharts| Orànic Fluorine Chemistry ðB!58MI 596!90Ł\ and\ _nally\Emele�us| The Chemistry of Fluorine and Its Compounds ðB!58MI 596!91Ł\ which covers mainly theinorganic chemistry of ~uorides[ Organic bromine compounds have been described by Jolles inBromine and its Compounds ðB!55MI 596!90Ł[

5[96[0[0 Four Similar Halogens

5[96[0[0[0 Tetra~uoromethane\ CF3

Treatment of metal carbides with ~uorine at 19>C for 89 min or with CoF2 at 339>C for 8 h leadsto mixtures of various ~uorocarbons among which CF3 predominates[ Thus\ Cr1C2 yields 80) CF3\as do Al3C2 "77)#\ B3C "77)#\ TiC "75)#\ Fe2C "75)#\ CaC1 "64)# and WC "56)# ð48JA795Ł[Fluorination of silicon carbide with F1 also leads to CF3 "Equation "0## ð49IS060Ł[

MnCm + F2 CF4 + C2F6 + C3F8 + C4F1020 °C, 90 min

68–91% 6–26% 2–14% 0–2%

(1)

relative yields:

M, n, m: see text for specification.

Tetra~uoromethane is furthermore formed\ in better than 49) yield\ upon ~uorination of acti!vated charcoal with F1 ð28JA1851Ł\ or upon ~uorination of graphite with PF2\ AsF2\ SF5\ CuF1\FeF2\ VF4 at 899Ð0199>C ð44USP1698075\ 44USP1698077\ 44USP1698089Ł\ PF4 at 1339>C ð47GEP0939900Łor HgF1 at 459Ð799>C ð44USP1698076Ł[

Fluorination "F1# of tri~uoromethane ð26JA0199\ 25CB188Ł or tetrachloromethane at 69>C in thepresence of As gives a relative yield of 63) CF3 with CClF2 as the main by!product ð39JA2366Ł[Treatment of tetrachloromethane ð20USP0850511Ł or tetraiodomethane ð37JCS1077Ł\ under readilyavailable laboratory conditions\ with BrF2 as ~uorinating agent also leads to tetra~uoromethane"Equation "1#\ Table 1#[

102Tetrahalomethanes

Table 0 Bibliographic information on the preparation\ melting points and boiling points of the tetra!halomethanes[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐFormula CA Re`[ no[ Beilsteins Handbuch der Gmelin Handbuch der M[p[ B[p[

Orànischen Chemiea Anorànischen Chemieb ">C# ">C#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐCX3

CF3 64!62!9 H 48\ I 7\ II 00\ III 24\ IV 15 81:82 −073c −029c

CCl3 45!12!4 H 53\ I 01\ II 11\ III 53\ IV 45 028:039 −12c 66c

CBr3 447!02!3 H 57\ I 06\ II 24\ III 81\ IV 74 143 77Ð89c 089c

Cl3 496!14!4 H 63\ I 08\ II 28\ III 093\ IV 87 162:172 057c 029Ð039 "0!1 torr#

CF2X

CClF2 64!61!8 III 31\ IV 23 181:182 −070c −79c

CBrF2 64!52!7 III 72\ IV 62 295:296 −057c −46 to −47c

CF2I 1203!86!7 III 87\ IV 81 203 −11[4c

CCl2X

CCl2F 64!58!3 H 53\ III 52\ IV 43 212 −000 to −009c 12[6c

CBrCl2 64!51!6 H 56\ II 20\ III 74\ IV 66 228 −5c 094c

CCl2I 483!11!8 H 60\ III 88\ IV 84 172:181\ 186:187\ 238 −08a 031a

CBr2X

CBr2F 242!43!7 I 06\ III 80\ IV 74 173:181\ 186\ 226:228 −62[5c 095Ð096c

CBr2Cl 483!04!9 H 57\ II 24\ III 80\ IV 74 172:181\ 186\ 238:240 44a 059a

CBr2I 03238!79!4 H 60\ IV 85 186:187\ 240 24d"dec[#

CI2X

CFI2 0384!38!3 186::187CClI2 03238!71!6 186:187\ 240CBrI2 447!05!6 H 63 186:187\ 240 002a

CF1X1

CBrClF1 242!48!2 IV 64 241:243\ 271:274 −048[4b\e −3f

CClF1I 319!38!4 IV 83 272\ 274 22f

CBrF1I 642!55!1 272\ 274 53[4Ð54[4g

"635 mmHg#

CCl1X1

CCl1F1 64!60!7 H 50\ III 37\ IV 39 243\ 272\ 274 −047c −18[7c

CBrCl1F 242!47!1 IV 65 243\ 272\ 274 −095b 40Ð41f

CCl1FI 319!37!3 IV 84 272\ 275 −096b 89b

CBrCl1I 39798!80!3 272\ 275

CBr1X1

CBr1F1 64!50!5 I 05\ III 76\ IV 79 241:243\ 264:267 −039h 12[7b\e

CBr1Cl1 483!07!2 H 57\ III 77\ IV 71 242:243\ 268:271 11a 024a

CBr1ClF 242!44!8 III 76\ IV 71 243\ 272\ 275 68Ð79c

CBr1FI 0367!93!1 272\ 275CBr1ClI 39798!82!5 272\ 275

CI1X1

CF1I1 0073!65!4 243\ 267:268 79[4b\e

CCl1I1 483!12!9 271 74i

CBr1I1 03948!89!5 271CClFI1 242!38!0 272\ 275CBrFI1 642!56!2 272\ 275CBrClI1 39798!83!6 272\ 275

CBrClFI

CBrClFI "R#CBrClFI "S#CBrClFI "2#CBrClFI " # 642!54!0 275*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

a Beilsteins Handbuch der Orànischen Chemie ðB!07MI 596!90\ B!17MI 596!90\ B!30MI 596!90\ B!48MI 596!90\ B!61MI 596!91Ł[b Gmelin Handbuch der Anorànischen Chemie ðB!63MI 596!91Ł[ c From Aldrich|s catalog of chemicals ðB!82MI 596!90Ł[d From Dehn ð98JA0119Ł[ e Calculated value[ f From Haszeldine ð41JCS3148Ł[ g From Burton et al[ ð71JFC"19#78Ł[ h From Millerand Smyth ð46JA19Ł[ i From Ho�land ð0776LA"139#114Ł[


Table 1 Synthesis of ~uorotrihalo!\ di~uorodihalo!\ tri~uorohalo! and tetra~uoromethanes with BrF2 and IF4[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Tetrahalomethane Relative Relative Temp[ Reaction Total Productsa

"relative amount 0# amount amount ">C# time yield ")# "ratio#of BrF2 of IF4

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐCCl3 9[22 RT 50 CCl1F1 "4# CCl2F "84#

9[5 −67 to RTb 78 CCl1F1 "74# CCl2F "04#9[73Ð0[95c RT 54Ð69 CCl1F1"04Ð32# CClF2 "46Ð74#

CCl2F 9[7 RT 85 CCl1F1

CBr3 9[22 −9 83 CBr2F "½099# CBr1F1 "trace#9[55 9 75 CBr2F "½11# CBr1F1

"½77# CBrF2 "trace#0d 9 83 CBrF2

9[52 89 2 h 72 CBr2F "trace# CBr1F1 "¼099#CBrF2 "trace# CF3 "trace#

CI3e 0[81 RT 37 CBr1F1 "22# CF3 "56#

9[77 RT to 89Ð099 29 min 54 CIF2

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐSource] Banks et al[ ð37JCS1077Ł[ a Volatile products were collected in cold traps[ b Tetrachloromethane was added to solid BrF2 in

carbon dioxide[ c The reaction was conducted in an autoclave[ d Bromine tri~uoride was added dropwise[ e Tetraiodomethane was addeddropwise over 1 h[

CI4 + BrF3 CBr2F2 + CF4RT

48% (33:67)

(2)

(1:2)

Tetra~uoromethane can furthermore be made by electrochemical means with HF as the ~uorinedonor[ Thus\ electrochemical ~uorination of trimethylamine yields mainly tris"tri~uoromethyl#!amine\ but also some tetra~uoromethane "Equation "2## ð41USP1505816Ł\ whereas electro!chemical ~uorination of dimethyl sul_de "Equation "3## yields CF3 as well as sulfur hexa~uorideand tri~uoromethylsulfur penta~uoride ð42JCS1261Ł[ Electrochemical ~uorination of acetic acid\acetyl chloride\ acetone\ trimethylacetic acid\ acetonitrile or methanol in HF with nickelanodes and iron cathodes as well as acetic acid with a KF¦2 HF melt have also been applied inthe synthesis of tetra~uoromethane ð38MI 596!90Ł as has the electrolysis of concentrated tri!~uoroacetic acid solutions with platinum electrodes "Equation "4## ð22BSB091Ł[

NMe3 N(CF3)3 + CHF3 + CF4 + NF3

HF, electrolysis(3)

SMe2 (CF3)2SF4 + CF3SF5 + CF4 + SF6

HF, electrolysis

97%(4)

2% 21% 60% 17%

CF3CO2H CF4 + C2F6 + CO2 + O2

electrolysis(5)

Other possibilities involve bond breaking in per~uoroalkenes\ for example oxidation of tetra!~uoroethylene with dioxygen which yields carbon dioxide and tetra~uoromethane "Equation "5##ð33USP1240289Ł[

(6)

F

F F

F

CF4 + CO2

O2

5[96[0[0[1 Tetrachloromethane\ CCl3

An old review on the preparation of tetrachloromethane exists ðB!37MI 596!90Ł[A major technical preparation uses chlorination of carbon disul_de at 29>C in the presence of an

iron catalyst with formation of tetrachloromethane and disulfur dichloride[ The actual chlorinatingagent is S1Cl1 and the sulfur formed is rechlorinated to S1Cl1 "Scheme 0# ð63MI 596!90\ B!82MI 596!92Ł[


Tetrachloromethane and disulfur dichloride can be separated by careful distillation in an inert gasstream ð64USP2773874Ł[

CCl4 + S2Cl2CS2 + 3Cl2

CCl4 + 6S

2S2Cl22Cl2 + 4S

2CCl4 + S2Cl2 + 2S2CS2 + 5Cl2

CS2 + 2S2Cl2

iron catalyst30 °C

Scheme 1

Tetrachloromethane is also commercially prepared by chlorination of chloromethane\ formed bychlorination of methane or\ more commonly\ by treatment of methanol with hydrogen chlorideð56MI 596!90\ 63MI 596!90\ 70MI 596!90\ B!80MI 596!91\ B!82MI 596!91Ł[ Another industrial procedure for themanufacture of chloromethanes uses a CuCl1:KCl melt as catalyst and chlorine source[ This meltis regenerated by an oxychlorination procedure which uses the HCl produced in the chlorinationreaction[ The overall reaction is presented in Equation "6# ðB!82MI 596!91Ł[

CH4 + HCl + O2 MeCl + higher chloromethanes + H2OCuCl2/KCl melt

(7)

Other processes involve heating of animal charcoal\ CO\ Cl1 and PCl2 at 399>C at 09 atm in anautoclave with AlCl2 and FeCl2 as catalyst\ which gives an 74) conversion to CCl3 ð56MI 596!90Ł[

Pyrolysis of hexachloroethane at 299Ð319>C yields a mixture of CCl3 and CCl1CCl1 ð49TFS184Ł[Increasing the temperature to 699Ð799>C causes further degradation of tetrachloroethylene totetrachloromethane "Scheme 1# ð26GEP57954\ 45BRP638397Ł\ and subjecting propene to chlorinolysisat 349Ð449>C produces a mixture of tetrachloroethylene and CCl3 the ratio of which ranges from24 ] 54 to 54 ] 24 depending on the exact conditions used "Equation "7## ðB!82MI 596!91Ł[

CCl4300–420 °C

Cl3C CCl3 CCl4 +

Cl

Cl Cl

Cl

700–800 °C

Scheme 2

Cl2

450–500 °CCCl4 +

Cl

Cl Cl

Cl

(8)

(35:65 to 65:35)

Thermal decomposition at 599>C of trichloroacetyl chloride gave a low yield "16)# of tetra!chloromethane in admixture with hexachloroethane "Table 2# ð28JA324Ł[ Under severe conditions"499>C\ in the presence of FeCl2# it is also possible to chlorinate benzene and naphthalene to CCl3in high yields "83)# ð56MI 596!90Ł[ Finally\ yields of 89) or more have been achieved by passingthiophosgene with gaseous MoCl4 or WCl5 at 7 atm over activated charcoal at 329>C ð56MI 596!90Ł[

5[96[0[0[2 Tetrabromomethane\ CBr3

Tetrabromomethane is formed in a relative yield of 83) with an admixture of 5) CClBr2 upontreatment of CCl3 with HBr:AlBr2^ overall yield 76) "Equation "8## ð40USP1442407Ł[ It can be made\furthermore\ from tribromomethane "or acetone# by oxidation with a sodium hypobromite solutioncontaining excess bromine ð21JA1914Ł[ This reaction is probably catalyzed by antimony"III# chlorideð0769LA"045#59Ł[

HBr/AlBr3CBr4 + CClBr3 (9)CCl4

87% (94:6)

Tetrabromomethane can also be made in a manner similar to the method used in the manu!facturing of CCl3\ but with CS1 and Br1 ðB!82MI 596!91Ł[


Table 2 Synthesis of tetrahalomethanes by thermal decomposition of trihaloacetyl halides or metal halo!acetates in the presence of halogen[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐStartin` material X1 Temp[ Yield Products Ref[

">C# ")# "ratio#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐCCl2COCl 599 29 CCl3"78# CCl2CCl2"00# 28JA324CCl2COBr 399 04 CBrCl2"56# CCl2CCl2"22# 28JA324CCl2COI 039 79 CBrCl2"83# CCl2CCl2"5# 28JA324CF2CO1Na I1

a 179 50 CF2Ib 40JCS473

CF2CO1K I1a 179 44 CF2I

b 40JCS473"CF2CO1#1Bag I1

a 179 21 CF2Ib 40JCS473

"CF2CO1#1Hgg I1a 149 24 CF2I

b 40JCS473"CF2CO1#1Pbg I1

a 149 15 CF2Ib 40JCS473

CF2CO1Ag Cl1a RT 89 CClF2

b 40JCS473Br1

a 49 77 CBrF2b 40JCS473

I1a 78Ð83 CF2I

b 40JCS473CCl2CO1K Cl1 009Ð019 "trace# CCl3 0766CB567

Br1 009Ð019 ×69 CBrCl2 0766CB567I1 009Ð019 "trace# CCl2I 0766CB567

ClI 009Ð019 "trace# CCl3 0766CB567CClF1CO1Agc Cl1

a 079Ð159 77 CCl1F1b 41JCS3148

Br1a 079Ð159 80 CBrClF1

b 41JCS3148I1

a 079Ð159 67 CClF1Ib 41JCS3148

CBrF1CO1Agd Br1a 079Ð159 70 CBr1F1

b 41JCS3148I1

a 079Ð159 4 CBrF1Ib 41JCS3148

CCl1FCO1Age Cl1a 079Ð159 52 CCl2F

b 41JCS3148Br1

a 079Ð159 47 CBrCl1Fb 41JCS3148

I1a 079Ð159 09 CCl1FIb 41JCS3148

CBrClFCO1Agf Cl1a 079Ð159 52 CBrCl1F

b 41JCS3148Br1

a 079Ð159 60 CBr1ClFb 41JCS3148*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

a Excess X1 "0[4 times the amount of metal haloacetate# was used[ b The products were continously removed by pumping through a coldtrap cooled with liquid air[ c Silver chlorodi~uoroacetate was prepared in 54) yield by permanganate oxidation of 0\0\1\2!tetrachloro!2\2!di~uoropropene\ followed by Ag1O:P1O4 treatment[ d Bromodi~uoroacetic acid was prepared "7) yield# by Swarts| method 92MI 596!90and converted to the silver salt by Ag1O:P1O4 treatment[ e Prepared as a mixture of CCl1FCO1Ag and CHClFCO1Ag "22 ] 56# by treatmentof chloro~uoroacetic acid with 19) excess Cl1\ followed by hydrolysis of the intermediate acid chloride[ The silver salts were prepared bytreatment of the corresponding acids with Ag1O:P1O4 "46)#[ f Silver bromochloro~uoroacetate was prepared in an overall yield of 12) bytreatment of bromo~uoroacetic acid with 19) excess Cl1\ followed by hydrolysis of the intermediate acid chloride[ The silver salt was preparedby treatment of the corresponding acids with Ag1O:P1O4[ g Barium tri~uoroacetate was prepared from tri~uoroacetic acid and Ba"OH#1[Mercury and lead salts were made similarly from tri~uoroacetic acid and mercury"II# and lead"II# oxide\ respectively[

5[96[0[0[3 Tetraiodomethane\ CI3

Tetraiodomethane may be made in the laboratory by heating CCl3 with CaI1¦1 H1O or LiI¦0[4H1O for 4 days at 89Ð81>C in an evacuated reaction vessel "yield 49Ð44)# ð04CR"045#541\ B!82MI 596!93Ł\ by treatment of acetone with KI:NaOCl "sat[# ð04CR"045#541Ł or by treating triiodomethanewith potassium hypoiodite under exclusion of light at 79Ð89>C ð16BSF0140Ł[

The synthesis of tetraiodomethane from acetone or triiodomethane su}ers from the fact that onlysmall quantities are preparable and that puri_cation is di.cult[

On the other hand\ the synthesis from tetrachloromethane and lower alkyl iodides allows thepreparation of larger quantities of tetraiodomethane\ giving nearly quantitative yields and a high!purity product\ for example starting from CCl3 in the presence of AlCl2 and iodoethane "0 ] 9[1 ] 3[9#ð49IS26Ł or iodomethane "0 ] 9[91 ] 3[1# ð34JA0531Ł as the iodine donor[ The chloromethane orchloroethane formed during the reaction is distilled o} from the reaction vessel "Equations "09# and"00##[

AlCl3 (cat.)

40 °C, 2 hCI4 + MeCl (10)CCl4 + MeI

92% (purity 99%)(1:4)

AlCl3 (cat.)

RT, 45 minCI4 + EtCl (11)CCl4 + EtI

quant.(1:4)

Crystalline CI3 can be prepared by irradiation of a mixture of CF2I and CO1 at 29 torr[ Carbondioxide seems\ under these conditions\ important for the formation of CI3 ð75MI 596!90Ł[


Tetraiodomethane may be puri_ed by recrystallization from chloroform or benzene in vacuoð34JA0531\ 26JOC65Ł[ When stored\ tetraiodomethane should\ like other iodine containing tetra!halomethanes\ be protected from oxygen\ water and light ð26JOC65Ł[

5[96[0[1 Three Similar and One Different Halogen

5[96[0[1[0 Tri~uoromethyl halides

"i# Chlorotri~uoromethane\ CClF2

Chlorotri~uoromethane also known as Freon 02\ is formed in 84) yield upon treatment oftetra~uoromethane with SbF2Cl1 = 1HF at 059>C and 69 atm ð36CI"L#316Ł\ and furthermore as a by!product "06)# in the preparation of CF3 from CCl3 with F1:As\ as mentioned previously ð39JA2366Ł[

Chlorotri~uoromethane has\ however\ been prepared in numerous ways such as by treatment ofCCl3 with ~uorine in the presence of iodine or CoF2 ð20ZAAC"190#134Ł\ as well as with HF anddi}erent oxometal ~uoride or metal ~uoride catalysts "Equation "01## ð45USP1633036\ 45USP1633037\45USP1634775\ 45USP1637066Ł and with antimony"V# chloride as catalyst at 79Ð059>C ð42USP1547816Ł[Chlorotri~uoromethane is also formed when CCl1F1 is kept in contact with oxoaluminum chlorideð43USP1583628Ł or\ under more severe conditions\ upon treatment of CCl1F1 with F1 in the presenceof Hg at 239Ð269>C ð39JA2366Ł[

AlF3

300 °CCCl2F2 + CCl3F + CClF3 (12)CCl4 + HF

90% (35:60:5)(1:1.25)

Chlorotri~uoromethane also constitutes the main product of the chlorination of graphite in thepresence of HF "Equation "02##[ This reaction has been optimized and found to be most e.cient whenconducted at 499>C[ The e}ects of di}erent catalysts have also been investigated ð44USP1698073Ł[

(13)Cl2, HF

500 °C, 3 hCCl3F + CCl2F2 + CClF3 + CF4 + haloethanesC

89% (7:21:53:14:5)

By use of BrF2 as ~uorinating agent chlorotri~uoromethane may be prepared in the laboratoryð37JCS1077Ł[ Banks et al[ ð37JCS1077Ł found that slow addition of the ~uorinating agent "BrF2 orIF4#\ lowering of the ratio of tetrahalomethane to ~uorinating agent as well as low temperature andan e.cient condensing system "in order to keep the more volatile intermediates in contact with BrF2

or IF4# favors the formation of tri~uorohalomethanes and tetra~uoromethane[ Bromine tri~uoridereacts smoothly\ but vigorously with CCl3 "Equation "03## and CBr3 whereas the reaction is violentin the case of CI3[ These reactions can be conducted at 9>C[ Iodine penta~uoride\ on the otherhand\ is less reactive and the reactions were conducted at 89Ð099>C "vide infra# "Table 1#[

(14)RT

CCl2F2 + CClF3CCl4 + BrF3

65–70% (15–43 to 57–85)(1:0.84–1)

Other possibilities include ~uorination of CHCl2 by the versatile ~uorinating agent CF2OF whichyields a mixture of CCl1F1 "5)#\ CClF2 "72)# and CF3 "00)# ð48JA0978Ł[ Carbonyl di~uoride mayby PCl4 treatment at 154Ð249>C be converted to a mixture of ~uorochloromethanes "Equation "04##as may phosgene by treatment with HF:Cl1:FeCl2 at 314>C for 06 h "Equation "05## ð46JA4790Ł[Calcium ~uoride:antimony penta~uoride treatment of phosgene at 499>C for 5 h ð45USP1646103Łleads to a mixture with CClF2 as the main product "Equation "06##[

(15)autoclave

CCl2F2 + CClF3 + CCl4 + COXY + CO2COF2 + PCl5

15% (67:33:0:–:–)(1:1.25)

(1:2.7) 35% (14:0:86:–:–)

265 °C, 16 h

350 °C, 12 hX, Y = Cl, F


(16)FeCl3/C

425 °C, 17 hautoclave

CCl2F2 + CClF3 + CF4COCl2 + HF + Cl2

72% (19:75:6)(6:6:1)

(17)CaF2/SbCl5

500 °C, 6 hCClF3 + CCl2F2 + CClF3 + CF4 + CCl4COCl2

(65:30:5:trace:trace)

Silver tri~uoroacetate when treated with chlorine also forms chlorotri~uoromethane ð40JCS473Ł\as does photochlorination of tri~uoromethane ð26JA0199Ł and cleavage of hexa~uoroethane withCl1 at 899>C ð38JA1388Ł[

Isotopically labeled CClF107F has been prepared by irradiation of a mixture of CClF2 and 07F08F[

CF207F was the main by!product ð68MI 596!90Ł[

"ii# Bromotri~uoromethane\ CBrF2

Bromotri~uoromethane may be synthesized in 89) yield under severe conditions "544Ð579>C#by treatment of tri~uoromethane with bromine ð35JA857\ 48USP1764143Ł or in 83) yield under milderconditions by ~uorination of tetrabromomethane at 9>C with BrF2 being added dropwise "Equation"07#\ Table 1# ð37JCS1077Ł[ Furthermore\ it can be made from tetrabromomethane with SbF2:Br1 at199>C ð49USP1420261Ł or in low yield with TiF3 at 019>C ð47JCS3134Ł[ Individual products areseparated from the reaction mixture by condensation in cold traps[

(18)BrF3, 0 °C

94%CF3BrCBr4

Hofmann rearrangement of tri~uoroacetamide with sodium hypobromite does not yield tri!~uoromethylamine\ but instead bromotri~uoromethane "Equation "08## ð46JCS29Ł[ This reaction isonly useful for the generation of CBrF2 and cannot be used for CClF2 and CF2I ð43JA4030Ł[Other degradative processes involve the Hunsdiecker reaction\ for example the heating of silvertri~uoroacetate and bromine at 54Ð029>C with formation of bromotri~uoromethane in 77) yield"Equation "19#^ Table 2# ð40JCS473\ 41JA0236Ł\ and the heating of tri~uoroacetyl bromide to 549>Ccausing elimination of carbon monoxide and formation of CBrF2 "Equation "10## ð44USP1693665Ł[Bromination\ with elemental bromine\ of tri~uoroacetic acid at 439>C "Equation "11## or tri!~uoroacetic acid anhydride at 299>C "Equation "12## in contact with activated carbon also leads tobromotri~uoromethane ð42USP1536822Ł[

(19)NaOBr

–NaNCOCF3BrCF3CONH2

(20)65–130 °C

CF3CO2Ag CF3Br + CO2

(21)650 °C

CF3COBr CF3Br + CO

(22)Br2, activated charcoal

540 °CCF3CO2H CF3Br + CO2

(23)Br2, activated charcoal

300 °C(CF3CO)2O CF3Br + CO2

Bromotri~uoromethane has also been made by plasma chemical means[ The reaction conditionswere applied for 3Ð4 min[ Thus\ treatment of hexa~uoroethane with bromine under the in~uence ofhigh!frequency electrical discharges "01 MHz\ 0 kV# at 3Ð19 torr gave 62) conversion and a 66)yield of CBrF2[ Treatment of CF2Cl under the same conditions gave only 12) conversion and a yieldof 50) ð64ZAAC"307#098Ł[ As was the case with chlorotri~uoromethane\ bromotri~uoromethane isalso formed upon bromination of hexa~uoroethane at 899>C ð38JA1388Ł[


Bromotri~uoromethane may\ furthermore\ be prepared by Cl:Br exchange[ Thus\ treatment ofCClF2 with HBr at 399>C in the presence of a ZnBr1:C catalyst leads to CBrF2 in 16) yieldð66BEP745122Ł[

"iii# Iodotri~uoromethane\ CF2I

The preparation and reactions of per~uoroiodoalkanes have recently been reviewed by Deev etal[ ð81RCR64Ł[

Synthesis in high yield "80)#\ of iodotri~uoromethane is possible by the Hunsdiecker reaction\for example from silver tri~uoroacetate and iodine\ and is used industrially "Equation "13## ð40JA1350\40JCS473Ł[ Sodium\ potassium\ barium\ mercury"II# and lead"II# tri~uoroacetate give in generallower yields of CF2I\ but the yield can be improved "79)# when sodium tri~uoroacetate is treatedwith excess iodine in the presence of CuI at 049>C in DMF ð56JOC722Ł or DMSO ð78MI 596!91Ł[Other decomposition reactions have also been applied\ such as the heating of tri~uoroacetyl chloridewith KI at 199>C for 5 h "Equation "14## giving 30) conversion and a yield of 58) iodo!tri~uoromethane under elimination of CO ð47JOC1905Ł\ or a procedure where tri~uoroacetyl ~uorideand lithium iodide at high temperature give CF2I in 69) yield "Equation "15## ð89CL702Ł[

(24)I2

CF3CO2Ag CF3I + AgI + CO2

91%

(25)KI, 200 °C

6 hCF3COCl CF3I + KCl + CO

69%

(26)LiI

CF3COF CF3I + LiF + CO70%

In the laboratory\ iodotri~uoromethane may also be conveniently made from the commerciallyavailable methyl chlorodi~uoroacetate "Equation "16## which\ on the other hand\ can be preparedfrom CF1CF1 "Scheme 2#[ Thus\ treatment of CClF1CO1Me with equimolar potassium ~uoride andiodine at 099Ð019>C in DMF and in the presence of catalytic amounts of CuI gives a yield of 69Ð79)[ CuI is essential for the high yield which in its absence drops to about 09)[ Omission ofpotassium ~uoride results in the formation of chlorodi~uoroacetamide in 03) yield as the onlyidenti_ed product[ Furthermore\ substitution of methyl chlorodi~uoroacetate with the bromo ana!logue gives a yield of 69) upon heating to 79>C in DMF for 4 h ð81CC796Ł[

(27)

CuI (cat.)100–120 °C, 2–3 h

DMFClCF2CO2Me + KF + I2 CF3I + CF2I2 + CH3I + CO2 + KCl

80–90% (88:12)

F

F F

F

ClCF2CF2I ClCF2COF ClCF2CO2MeICl fuming H2SO4 MeOH

Scheme 3

Other reactions include the reaction of tri~uoronitrosomethane with iodine at 49Ð69>C\ with ayield of 79Ð84) ð54IZV0762Ł\ and\ in low yield\ the ~uorination of CI3 with TiF3 ð47JCS3134Ł\ orwith IF4 "Table 1# in a yield of 54) ð37JCS1077\ 38JCS1745Ł[ Due to the inferior reactivity of iodinepenta~uoride compared to bromine tri~uoride\ the reaction requires heating at 89Ð099>C for 29min[

Furthermore\ prolonged UV irradiation of methyl tri~uoromethyl sul_de or bis"tri~uoromethyl#sul_de in the presence of sources of iodine radicals yields 29Ð53) iodotri~uoromethaneð61JCS"P0#0495\ 63JCS"P0#0695Ł[

Iodotri~uoromethane can\ like bromotri~uoromethane\ be made by plasma chemical means "seethe previous section#\ but only in modest yields[ Thus\ treatment of hexa~uoroethane with iodine


under the in~uence of high frequency electrical discharges "01 MHz\ 0 kV# at 3Ð19 torr gave 29)conversion\ but only a yield of 4) CF2I[ Treatment of CF2Cl under the same conditions gave only03) conversion but a yield of 17) ð64ZAAC"307#098Ł[

"iv# Tri~uoromethyliodine"III# compounds\ "CF2#nIZ2−n "n�0\ 1#

The preparation and isolation of CF2IF1 ð48AG413Ł\ CF2ICl1 ð78JFC"34#390Ł\ CF2I"ONO1#1ð63IC1700Ł and CF2I"OCOCF2#1 ð65JFC"7#066Ł have been reported in the literature[Tri~uoromethyliodine"III# di~uoride\ for instance\ is prepared by oxidative ~uorination "F1# at−79>C of tri~uoroiodomethane with trichloro~uoromethane as solvent ð48AG413Ł[

Bis"tri~uoromethyl#iodine derivatives "n�1\ Z�ONO1\ OCOCF2\ F\ Cl# have been prepared byTyrra and Naumann ð80CJC216Ł by tri~uoromethylation of tri~uoromethyliodine"III# dichloride\dinitrate\ di~uoride or bis"tri~uoroacetate# with either Cd"CF2#1 = 1 glyme or Bi"CF2#2[ None of thesewere\ however\ isolated\ but only detected and investigated by NMR[

5[96[0[1[1 Trichloromethyl halides

"i# Trichloro~uoromethane\ CCl2F

Trichloro~uoromethane has been widely used as refrigerant and propellant and is known asFreon 00[ Industrial preparations include Cl:F exchange of HF with CCl3\ in a gas phase reactionat 049>C with catalysis from aluminum\ chromium\ nickel or calcium ~uoride[ The main by!productis Freon 01\ CCl1F1[ Alternatively\ the reaction may be conducted in the liquid phase under pressureat 099>C and with antimony ~uoride catalysis ð45USP1628878\ B!82MI 596!91Ł[

The product of the reaction between tetrachloromethane and HF is highly dependent on therelative amounts of CCl3 and HF as well as on the temperature[ At an HF ]CCl3 ratio of 0 ] 8\ atemperature of 324>C and a pressure of 69 atm\ the total yield is 84)\ consisting of 66) CCl2F\07) CCl3 and 4) CCl1F1 "Equation "17## ð36IEC393Ł[ In liquid phase reactions antimony chlorides\such as SbCl2\ together with a certain amount of chlorine or even better\ SbCl4 have been usedð36JA836Ł[

CCl4 + HF CCl3F + CCl4 + CCl2F2

cat.435 °C, 70 atm

95% (77:18:5)

(28)

Trichloro~uoromethane is also formed as one of the minor products in the reaction of graphitewith Cl1 and HF at 499>C as described above ð44USP1698073Ł[

Sodium hexa~uorosilicate under pressure at 169>C "Equation "18## ð48AG163Ł\ titanium tetra!~uoride ð47JCS3134Ł\ chlorine tri~uoride:cobalt tri~uoride at 14>C ð42JCS0952Ł\ iodine penta~uorideat 29Ð24>C ð20ZAAC"190#134Ł and bromine tri~uoride "Table 1\ Equation "29## ð37JCS1077Ł are alsouseful as ~uorinating agents for tetrachloromethane[

(29)CCl4 + Na2SiF6 CCl3F + CCl2F2 + CClF3 + NaCl + SiF4

autoclave270 °C, 2 h

~100% (33:66:trace)

(30)CCl4 + BrF3 CCl2F2 + CCl3FRT

61% (5:95)(1:0.33)

In the laboratory the Hunsdiecker reaction may be applied for the synthesis of trichloro!~uoromethane "in 52) yield# from silver dichloro~uoroacetate and chlorine "Table 2\ Equation"20## ð41JCS3148Ł[


(31)CCl2FCO2Ag + Cl2 CCl3F + CO2 + AgCl180–260 °C

63%(1:1.5)

"ii# Bromotrichloromethane\ CBrCl2

Treatment of tetrachloromethane with HBr:AlBr2 leads to bromotrichloromethane ð23JA0344Ł[Bromotrichloromethane is formed by treatment of trichloromethane with bromine at 114Ð349>C

ð26CR"193#0816\ 36JCS563Ł\ or in 79Ð74) yield at 319Ð349>C by recycling the material with b[p[ below64>C ð41MI 596!90Ł\ and\ furthermore\ under the in~uence of light ð31JA0231Ł[

Older methods involve heating potassium trichloroacetate with bromine at 019>C "Equation "21#\Table 2# ð0766CB567Ł or heating trichloromethanesulfonyl bromide with ethanol at 099>Cð0758ZC513Ł[ Low yields "09)# of bromotrichloromethane have been achieved by heating tri!chloroacetyl bromide to 399>C[ Most of the trichloroacetyl bromide was recovered "Table 2#ð28JA324Ł[

(32)Cl3CCO2K + Br2 CBrCl3 + CO2 + KBr110–120 °C

>70%

The less easily available tetrahalomethanes may\ however\ also be prepared by base!catalyzed{{halogen dance|| "Scheme 3# ð81MI 596!92\ 82BSF488Ł[

Heating chloroform with tetrabromomethane and dibenzoyl peroxide ð40USP1442799Ł or N!bromosuccinimide ð41MI 596!91Ł also yields bromotrichloromethane[

F3CCCl3 + CBr4

base/solvent

RT, 0.5–11 hF3CCCl3 + CBr4

base/solvent

RT, 0.5–11 h

CBrCl3 CCl4 + CBr2Cl2 + CBr3Cl + CBr4base

solvent: DMF, CH2Cl2base: TBAF, NaOPh, NaOH, KOH, NaOEt, NaNH2

Scheme 4

F3CCBrCl2 + F3CCBr2Cl + F3CCBr3 + CBrCl3 + CBr2Cl2 + CBr3Cl

"iii# Trichloroiodomethane\ CCl2I

Good yields "64)# of trichloroiodomethane in admixture with hexachloroethane "05)# areachieved by distillation "039>C# at atmospheric pressure of trichloroacetyl iodide "Scheme 4\Table 2# ð28JA324Ł\ prepared from hydrogen iodide and trichloroacetyl chloride[ Treatment ofbromotrichloromethane with aluminum iodide leads to trichloroiodomethane ð42JCS811Ł[

Cl3CCOCl Cl3CCOI Cl3CCCl3 + CCl3IHI

distillation140 °C

80% (6:94)Scheme 5

Trichloromethane treated with iodine and sodium hydroxide at 9>C for 04 h\ gave 09) di!chloroiodomethane as well as 0) trichloroiodomethane[ The iodinating agent in this medium issodium hypoiodite generated in situ[ Use of tetrachloromethane\ excess iodine and sodium hydroxideat 9>C for _ve days gave trichloroiodomethane in less than 4) yield[ An attempt to iodinatetetrachloromethane with NaI in acetone failed ð68JCED140Ł[


5[96[0[1[2 Tribromomethyl halides

"i# Tribromo~uoromethane\ CBr2F

Tribromo~uoromethane is formed as a coproduct "20)# in the reaction of "dibromo!~uoromethyl#triphenylphosphonium bromide\ formed from triphenylphosphine and CFBr2 inTHF\ with iodine monobromide in tetraglyme "Scheme 5# ð71JFC"19#78Ł\ and under controlledreaction conditions\ in high yield "83)# upon ~uorination of tetrabromomethane with brominetri~uoride "Equation "22#\ Table 1# ð37JCS1077Ł[

R3P + CFXYZsolvent

[R3PCFXY]+ Z–

[R3PCFXY]+ Z– + X'Y' + KF CFXYX'solvent'

solvent' = triglyme, tetraglyme or DMFsolvent = THF, diethyl ether or triglyme

R = Ph or (NMe2)X, Y, Z = F, Cl or Br

X', Y' = Cl, Br, IScheme 6

CBr4 + BrF3~0 °C

CBr3F + CBr2F2 (33)(1:0.33) 94% (100:trace)

Furthermore\ it is available by ~uorination of tetrabromomethane with antimony tri~uoride"08Ð81) yield# ð07CB558\ 46JA4543\ 47BSB565\ 48JCS02Ł[ Birchall and Haszeldine heated tetrabromo!methane with antimony tri~uoride and bromine "1 ] 0 ] 9[0# 0 h at 019Ð029>C\ followed by 29 min at049Ð059>C\ with a yield of 54Ð69) after distillation "Equation "23## ð48JCS02Ł[ Silver ~uoride hasalso been applied as ~uorinating agent in a distillation apparatus*allowing bromotri~uoromethaneto distil out of the reaction mixture ð07CB558Ł[

(34)CBr4 + Br2 + SbF3 CBr3F(2:0.1:1) 65–70%

i, 120–130 °C, 1 hii, 150–160 °C, 0.5 h

"ii# Tribromochloromethane\ CBr2Cl

Tribromochloromethane is formed as the main product "relative yield 31)# after base!catalyzed{{halogen dance|| reactions "Scheme 3# ð81MI 596!92\ 82BSF488Ł[ Thus\ after treatment of CF2CCl2:CBr3

with KOH in DMF at RT for 3 h\ tribromochloromethane is formed with the following by!products]CF2CCl1Br "relative yield 21)#\ CF2CClBr1 "10)# and CBr1Cl1 "08)# ð81MI 596!92Ł[

Dibromochloronitrosomethane may be re~uxed with bromine for 2 h giving a 84) yield oftribromochloromethane[ Dibromochloronitrosomethane is in turn accessible from Br1C1NOH"Scheme 6# ð21CB435Ł[

ClBr2CNO CBr3Cl95%

Br2, reflux, 3 hN

Br

Br OH

Scheme 7

75–80%

i, HgCl2 (aq.)ii, Br2, NaOAc

Treatment of CCl3 with an equimolar amount of Br1 for 1 h at 114>C leads to tri!bromochloromethane in admixture with bromotrichloromethane and dibromodichloromethaneð0781CB077Ł[ Trichloromethane heated with bromine for 03 h at 114Ð164>C ð26CR"193#0816Ł as wellas HBr:AlCl2 treatment of tetrachloromethane gives tribromochloromethane[ In the latter reaction\HBr is bubbled into a solution of CCl3 and AlCl2 and the temperature raised to 89>C[ The productcontains 5) tribromochloromethane and 83) tetrabromomethane with an 76) conversion oftetrachloromethane[


"iii# Tribromoiodomethane\ CBr2I

Treatment of CHBr2 with KI\ NaOCl and NaOH for 13 h gave mainly CHBr1I "09)# and onlytraces "9[0)# of tribromoiodomethane could be detected[ The same reaction conditions were alsoapplied to CBr3 for six days\ but again only a very low yield "³0)# of CBr2I was obtained[ On theother hand\ when CBr3 was treated with NaI in acetone for 4 min a yield of more than 29)CBr2I was observed\ although the product was contaminated with CBrI2 and brominated acetone"Equation "24## ð68JCED140Ł[ According to an old procedure by Dehn ð98JA0119Ł it should\ however\be possible to prepare tribromoiodomethane from tribromomethane and nitrosyl iodide[ Dehnreported the product as a solid darkening at 24>C[

CBr4 CBr3I + CBrI3 + brominated acetoneNaI, acetone

5 min(35)

~30%

5[96[0[1[3 Triiodomethyl halides

"i# Fluorotriiodomethane\ CFI2 and chlorotriiodomethane\ CClI2

Fluorotriiodomethane and chlorotriiodomethane still await preparation\ but theoretical dis!cussions of their physical properties are on record ð47MI 596!90\ 48MI 596!92\ 55ZOB0244\ 61MI 596!90\65ZC266\ 66MI 596!90\ 68JMR448\ 72MI 596!90\ 80MI 596!90Ł[

"ii# Bromotriiodomethane\ CBrI2

Bromotriiodomethane has been prepared by Dehn ð98JA0119Ł by treatment of triiodomethanewith NaOBr[ It is an unstable solid which liberates iodine upon exposure to light or upon dissolution[Bromotriiodomethane has also been reported as a by!product in the Finkelstein reaction mentionedabove\ that is the treatment of tetrabromomethane with sodium iodide in acetone "Equation "24##ð68JCED140Ł[

5[96[0[2 Two Similar Halogens

5[96[0[2[0 Di~uoromethylene dihalides

"i# Bromochlorodi~uoromethane\ CBrClF1

Bromochlorodi~uoromethane may be prepared in 80) yield by the heating of silver chloro!di~uoroacetate with bromine "Equation "25#\ Table 2# ð41JCS3148Ł[

(36)CClF2CO2Ag + Br2 CBrClF2 + CO2 + AgBr180–260 °C

(1:1.5) 91%

Bromochlorodi~uoromethane is formed\ but only in very low yield "4)#\ in the reaction oftris"dimethylamino#"chlorodi~uoromethyl#phosphonium chloride\ formed from tris"dimethyl!amino#phosphine and CF1Cl1 in triglyme\ with bromine in triglyme "Scheme 5# ð71JFC"19#78Ł[

Trabalka et al[ describe in a patent ð70MIP57244Ł the formation of bromochlorodi~uoromethaneby heating of chlorodi~uoromethane with bromine and chlorine at 499Ð799>C[ Other syntheticmethods include the preparation from chlorodi~uoromethane\ bromine and oxygen with catalysisfrom chromium trioxide at 499>C[ The yield was 75) and the reaction product consisted ofCBrClF1\ CBr1F1 and CHClF1 "47 ] 6 ] 24^ Equation "26## ð48USP1760163Ł[ Other sources are bro!modi~uoromethane by vapor phase chlorination ð42USP1528291Ł or UV irradiation of a mixture of


chlorodi~uoroiodomethane and bromine ð41JCS3148Ł[ Finally\ treatment of 0\2!dichloro!0\0\2\2!tetra~uoroacetone with bromine at 479Ð549>C yields bromochlorodi~uoromethane ð48USP1774349Ł[

(37)CHClF2 + Br2 + O2 CBrClF2 + CBr2F2 + CHClF2

CrO3

500 °C 86% (58:7:35)

"ii# Chlorodi~uoroiodomethane\ CClF1I

Chlorodi~uoroiodomethane has been prepared by Haszeldine "Equation "27#\ Table 2#ð41JCS3148Ł in 67) yield by heating silver chlorodi~uoroacetate with iodine[ This halomethane is\however\ unstable and liberates iodine on exposure to O1 or light ð41JCS3148Ł[

(38)CClF2CO2Ag + I2 CClF2I + CO2 + AgBr180–260 °C

78%(1:1.5)

Di~uorocarbene is generated from methyl chlorodi~uoroacetate by treatment with LiCl:HMPAand may\ when formed in the presence of I1 or IBr\ be used to prepare chlorodi~uoroiodomethanein 04) yield "contaminated with 4) CF1I1# and 29) "contaminated with 09) CBrF1I#\ as shownin Equations "28# and "39#\ respectively ð67JOC1532Ł[

(39)CClF2CO2Me + LiCl/HMPA + I2 CClF2I + CF2I2

90–95 °C, 48 htriglyme

20% (75:25)

(40)CClF2CO2Me + LiCl/HMPA + IBr CClF2I + CBrF2I

90–95 °C, 48 htriglyme

40% (75:25)

Another method is the reaction of ð"Me1N#2P"CF1Cl#ŁCl\ formed from tris"dimethylamino#!phosphine and CF1Cl1 in triglyme\ with dry potassium ~uoride and iodine at 9>C for 1 h andthen overnight at room temperature[ The isolated yield of CClF1I is 23) "Scheme 5# ð71JFC"19#78Ł[

Chlorodi~uoroiodomethane can\ like bromo! and iodotri~uoromethane\ be made by plasmachemical means\ but only in modest yields[ Thus\ treatment of chlorotri~uoromethane with iodineunder the in~uence of high!frequency electrical discharges "01 MHz\ 0 kV# at 3Ð19 torr gave 6)conversion\ and a relative yield of 10) ð64ZAAC"307#098Ł[

"iii# Bromodi~uoroiodomethane\ CBrF1I

When di~uorocarbene is generated in the presence of IBr\ bromodi~uoroiodomethane is formedas a by!product "09)# "Equation "39## ð67JOC1532Ł[ Another method is the reaction of "bromo!di~uoromethyl#triphenylphosphonium bromide\ formed from triphenylphosphine and CF1Br1 intriglyme\ with dry potassium ~uoride and iodine in triglyme[ The isolated yield of CBrF1I is 30)"Scheme 5# ð72JFC"12#228\ 71JFC"19#78Ł[

Bromodi~uoroiodomethane is one of the few tetrahalomethanes which could not be preparedexcept in poor yield "³4)# by the Hunsdiecker method "Table 2#[

5[96[0[2[1 Dichloromethylene dihalides

"i# Dichlorodi~uoromethane\ CCl1F1

The industrial preparation of dichlorodi~uoromethane\ known as Freon 01\ involves halogenexchange of CCl3 with HF\ as described above for CFCl2 ðB!82MI 596!91Ł[

At a HF ]CCl3 ratio of 3 ] 8\ a temperature of 389>C and a pressure of 69 atm\ the total yield inthe reaction between CCl3 and HF has been reported to be 48)\ consisting of 68) CCl1F1 and


10) CCl2F "Equation "30## ð36IEC393Ł\ whereas in the presence of SbCl2 and Cl1 at 009>C and29 atm\ CCl1F1 constitutes 89) of the product ðB!81MI 596!93Ł[ Furthermore\ treatment of phosgenewith chlorine and anhydrous hydrogen ~uoride at 314>C in the presence of FeCl2:C also yields amixture consisting of CCl1F1\ CClF2 and CF3 "Equation "06## ð46JA4790Ł[ Trichloromethane does\as mentioned above\ also form a CClmFn mixture when treated with CF2OF ð48JA0978Ł\ anddichlorodi~uoromethane is formed as one of the minor products in the reaction of graphite withCl1 and HF at 499>C as described above ð44USP1698073Ł[

(41)CCl4 + HF CCl2F2 + CCl3F490 °C, 70 atm

59% (79:21)(9:4)

In the laboratory\ dichlorodi~uoromethane may be prepared in high yield "85)# by ~uorinationof CCl2F with BrF2\ or as the main product of the ~uorination of CCl3 with BrF2 at −67>C:RTin a total yield of 78) "Scheme 7\ Table 1#[ Trichloro~uoromethane is the only by!productð20USP0850511\ 37JCS1077Ł[

CCl4 + BrF3 CCl2F2 + CCl3F–78 °C to RT

89% (85:15)(1:0.6)

CCl4 + BrF3 CCl2F2

96%(1:0.8)

RT

Scheme 8

Treatment of tetrachloromethane with sodium hexa~uorosilicate under pressure at 169>C in anautoclave yields a mixture of CClnF3−n with dichlorodi~uoromethane as the major product "Equa!tion "18## ð48AG163Ł[

Degradative reactions forming CCl1F1 include the chlorinolysis at 449>C of 0\0!di~uoroethane\formed by treatment of acetylene with HF ðB!48MI 596!91Ł and the heating of silver chloro!di~uoroacetate with chlorine "Equation "31#\ Table 2# ð41JCS3148Ł[

CClF2CO2Ag + Cl2 CCl2F2 + CO2 + AgCl180–260 °C

(1:1.5)

(42)88%

Dichlorodi~uoromethane may _nally also be made by electrolysis of chlorodi~uoroacetic acidð22BSB091Ł[

"ii# Bromodichloro~uoromethane\ CBrCl1F

Bromodichloro~uoromethane has been prepared by Haszeldine ð41JCS3148Ł by use of theHunsdiecker reaction\ in 47) yield by heating silver dichloro~uoroacetate with bromine "Equation"32## and in 52) yield by heating silver bromochloro~uoroacetate with chlorine "Equation "33#\Table 2#\ and also by bromination of dichloro~uoromethane at 364>C "30) conversion\ yield 67)#ð45USP1644203\ 46JA3048\ 48JA1967Ł[

CCl2FCO2Ag + Br2 CBrCl2F + CO2 + AgBr180–260 °C

(1:1.5)

(43)58%

CBrClFCO2Ag + Cl2 CBrCl2F + CO2 + AgCl180–260 °C

(1:1.5)

(44)63%

"iii# Dichloro~uoroiodomethane\ CCl1FI

Dichloro~uoroiodomethane has been prepared in poor yield by heating silver dichloro!~uoroacetate with iodine[ Dichloro~uoroiodomethane turned out to be unstable to storage at RT[It forms di}erent haloethanes with liberation of iodine ð41JCS3148Ł "Table 2#[

It has been prepared in 33) yield "52Ð62) yield according to Fried and Miller ð48JA1967Ł# by a


Finkelstein reaction from bromodichloro~uoromethane:NaI:acetone in a closed vessel for 2 h at019>C "Equation "34## ð46JA3048Ł[

(45)CBrCl2F + NaI CCl2FI + NaBr

acetone120 °C, 3 h

44–73%

"iv# Bromodichloroiodomethane\ CBrCl1I

Bromodichloroiodomethane has not been prepared yet\ but theoretical discussions of its physicalproperties are on record ð61MI 596!90\ 68JMR448\ 80MI 596!90Ł[

5[96[0[2[2 Dibromomethylene dihalides

"i# Dibromodi~uoromethane\ CBr1F1

Dibromodi~uoromethane may be prepared in 72) as the only product by ~uorination of tetra!bromomethane with IF4 "Equation "35##\ as the major product "relative yield 65)# by ~uorinationwith BrF2\ and as a minor product "relative yield 05)# by ~uorination of tetraiodomethane withIF4 "Table 1# ð37JCS1077Ł[ Fluorination of tetrabromomethane with TiF3 forms dibromo!di~uoromethane in low yield as a mixture with bromotri~uoromethane ð47JCS3134Ł[ Furthermore\CBr1F1 is formed in high yield "70)# by the heating of silver bromodi~uoroacetate with bromine"Equation "36#\ Table 2# ð41JCS3148Ł[

CBr4 + IF5 CBr2F2 + CBr3F + CBrF3 + CF490 °C, 3 h

(46)

83% (100:trace:trace:trace)(1:0.6)

CBrF2CO2Ag + Br2 CBr2F2 + CO2 + AgBr180–260 °C

(47)

81%(1:1.5)

Other methods involve vapor phase bromination of di~uoromethane at 499>C "50) conversion^the product is a mixture of CHBrF1 and CBr1F1 ð42USP1528290Ł# and treatment of di~uoromethanewith a mixture of bromine and chlorine at 249>C ð42USP1547975Ł[ Furthermore\ a low yield isobtained from bromochlorodi~uoromethane and HBr:Br1 at 599>C "55) conversion^ the productis a 83 ] 5 mixture of CHBrF1 and CBr1F1 ð45USP1618576Ł#\ or from tribromo~uoromethane\ HF anda chromium oxo~uoride catalyst at 149>C ð45USP1634775Ł[ Reaction between tetrabromomethane\HF and an aluminum oxo~uoride catalyst at 129Ð149>C\ 0\2!dichloro!0\0\2\2!tetra~uoroacetoneand bromine at 479Ð549>C ð48USP1774349Ł or the heating of tetrabromomethane with AgF "0 ] 1#\allowing distillation from the reaction mixture to occur ð07CB558Ł\ all lead to dibromodi~uoro!methane[

Dibromodi~uoromethane is formed\ but only in a very low yield "2)#\ in the reaction of tris!"dimethylamino#"chlorodi~uoromethyl#phosphonium chloride\ formed from tris"dimethylamino#!phosphine and CF1Cl1 in triglyme\ with bromine in triglyme "Scheme 5# ð71JFC"19#78Ł[

"ii# Dibromodichloromethane\ CBr1Cl1

Bromotrichloromethane disproportionates in the presence of tetrabutylammonium ~uoride to amixture of tetrachloromethane\ dibromodichloromethane\ tribromochloromethane and tetra!bromomethane ð82BSF488Ł[ Other bases and solvent systems have also been tried in such base!catalyzed {{halogen dance|| reactions[ The individual halomethanes were obtained by fractionaldistillation "Scheme 3# ð81MI 596!92Ł[

It is also obtained\ in admixture with other halomethanes\ from tetrachloromethane treated withbromine tri~uoride in the presence of AlCl2 or BBr2[

Dichloromethane and bromine react under formation of dibromodichloromethane on illumi!nation ð31JA0231Ł or after heating in a sealed vessel at 119Ð149>C for more than a week


ð0776LA"139#081Ł[ Furthermore\ impure CBr1Cl1 is obtained upon treatment of trichloromethanewith bromine in a closed reaction vessel at 114Ð164>C ð26CR"193#0816Ł or by heating dichloro!bromonitrosomethane with bromine "vide supra# ð21CB435Ł[

"iii# Dibromochloro~uoromethane\ CBr1ClF

Dibromochloro~uoromethane is formed in 60) yield upon heating of silver bromo!chloro~uoroacetate with bromine "Equation "37#\ Table 2# ð41JCS3148Ł and by vapor phase bro!mination of dichloro~uoromethane at 549>C ð45USP1644203Ł[

(48)CBrClFCO2Ag + Br2 CBr2ClF + CO2 + AgBr180–260 °C

71%(1:1.5)

"iv# Dibromo~uoroiodomethane\ CBr1FI

Dibromo~uoroiodomethane is formed as the major product "46)# in the reaction of "dibromo!~uoromethyl#triphenylphosphonium bromide\ formed from triphenylphosphine and CBr2F inTHF\ with iodine in tetraglyme[ The crude product is\ however\ contaminated with substantialamounts of other halomethanes "Scheme 5# ð71JFC"19#78Ł[

"v# Dibromochloroiodomethane\ CBr1ClI

Dibromochloroiodomethane still awaits preparation\ but theoretical discussions of its physicalproperties are on record ð61MI 596!90\ 68JMR448\ 80MI 596!90Ł[

5[96[0[2[3 Diiodomethylene dihalides

"i# Di~uorodiiodomethane\ CF1I1

Di~uorodiiodomethane has been prepared in low yield "16)# by ~uorination of CI3 with HgF1

in 0\1!dichlorobenzene[ Excessive ~uorination is minimized by distillation of the CF1I1 formed inthe reaction ð73JOC194\ 74DIS"B#739Ł[ A better method has\ however\ been reported by Su et al[ð81CC796Ł who discovered a convenient method for obtaining pure CF1I1 in fair yield "49Ð59)isolated yield^ 79) by 08F NMR#[ Treatment of methyl bromodi~uoro! or chlorodi~uoroacetatewith equimolar amounts of KI\ I1 and a catalytic amount of CuI leads to the formation of CF1I1

"Equation "16##[ This method is\ however\ somewhat compromized by di.culties in the separationof CH2I and CF1I1[ Pure di~uorodiiodomethane is obtained from potassium bromodi~uoroacetateby heating with equimolar amounts of KI\ CuI and I1 in DMF at 39>C for 09 h[ The use of only acatalytic amount of CuI causes the yield to drop to 09) "Equation "38## ð81CC796Ł[

(49)CBrF2CO2K + KI + CuI + I2 CF2I2 + KBr + CO2

90% (50–60% isolated)

DMF40 °C, 10 h

"ii# Dichlorodiiodomethane\ CCl1I1

Dichlorodiiodomethane has been prepared by Ho�land in 0776 ð0776LA"139#114Ł by treatment ofCH1Cl1 with Br1:I1 "0 ] 3:3# at 099Ð199>C for several weeks[ Distillation of the crude product gavedichloroiodomethane and dichlorodiiodomethane[ Dichlorodiiodomethane melts at 74>C underliberation of iodine and is probably unstable in solution ð0776LA"139#114Ł[


"iii# Bromo~uorodiiodomethane\ CBrFI1

Bromo~uorodiiodomethane is formed as a minor by!product "04)# in the reaction of "dibromo!~uoromethyl#triphenylphosphonium bromide\ formed from triphenylphosphine and CBr2F inTHF\ with iodine in DMF "Scheme 15# ð71JFC"19#78Ł[

"iv# Dibromodiiodomethane\ CBr1I1^ chloro~uorodiiodomethane\ CClFI1^ andbromochlorodiiodomethane\ CBrClI1

Dibromodiiodomethane\ chloro~uorodiiodomethane and bromochlorodiiodomethane still awaitpreparation\ but theoretical discussions of their physical properties are on record ð47MI 596!90\ 48MI596!92\ 55ZOB0244\ 61MI 596!90\ 65ZC266\ 66MI 596!90\ 68JMR448\ 72MI 596!90\ 80MI 596!92Ł[

5[96[0[3 Bromochloro~uoroiodomethane\ CBrClFI

Bromochloro~uoroiodomethane\ although often mentioned as the prototype of a chiralcompound\ has not been prepared yet[ MO calculations indicate that it is the second least stablechiral halomethane judged from the enthalpies of formation ð89BCJ0167Ł[ The only chiral halo!methane which has been prepared is CHBrClF\ and it has been shown that this derivative hydrolyzesmuch faster than other mixed halomethanes ð45JA368Ł^ this may also be the case with bromo!chloro~uoroiodomethane[

It would be interesting to try the Hunsdiecker reaction on silver bromochloro~uoroacetate whichreacts with both chlorine and bromine as mentioned above[ It may\ however\ turn out to be a verylow yielding reaction\ as was the case with the treatment of silver bromodi~uoroacetate with iodine"Table 2# ð41JCS3148Ł[

Theoretical discussions of the physical properties of so far unsynthesized tetrahalomethanes areon record ð47MI 596!90\ 48MI 596!90\ 55ZOB0244\ 61MI 596!90\ 65ZC266\ 66MI 596!90\ 68JMR448\ 72MI 596!90\80MI 596!90Ł[

5[96[1 METHANES BEARING THREE HALOGENS

5[96[1[0 Three Halogens and a Chalcogen

Trihalomethoxy as well as trihalomethylthio groups may be regarded as superhalo`ens and behaveas such[ They are\ for example deactivating and ortho!\ para!directing substituents in electrophilicaromatic substitution[ As superhalo`ens\ they have been used as alternative substituents to cir!cumvent existing patents and to impart increased lipophilicity to compounds relative to their halogensubstituted counterparts[ For more information see a comparison and discussion on trihalomethyl"and other pseudohalogens# vs[ halogen by Haas\ who has made a large contribution to this synthetic_eld ð71CZ128\ 73MI 596!90Ł[

The subject of trihalomethoxy and trihalomethylthio containing compounds has previously beenreviewed by Marhold ð72HOU"E3#514\ 72HOU"E3#0192Ł\ Hocker ð72HOU"E3#0257Ł and McClinton andMcClinton ð81T5444Ł[

5[96[1[0[0 Three halogens and an oxygen function

"i# Trihalomethanols\ CHal2OH

Tri~uoromethanol is a rather unstable compound which\ above −19>C\ eliminates hydrogen~uoride under formation of carbonyl ~uoride[ It was therefore not synthesized until 0866\ whenSeppelt prepared tri~uoromethanol by treating tri~uoromethyl hypochlorite with HCl at −019>Cð66AG214Ł[

118Three Halo`ens

"ii# Trihalomethyl ethers\ CHal2OR

Aryl tri~uoromethyl ethers may be prepared from the corresponding phenols by treatment withtetrachloromethane and hydrogen ~uoride\ with the exception of phenols with ortho!substituentscapable of hydrogen bonding to the hydroxy group[ The yields are generally best when electron!withdrawing substituents are present ð68JOC1896Ł[ Chlorine may be used as such and later removedby hydrogenation ð76JA2697Ł[ The reaction is catalyzed by antimony trichloride and probably passesthrough the trichloro derivative ð68JOC1896Ł[

Trichloromethyl ethers "aryl and alkyl# can in turn be transformed to tri~uoromethyl ethers bytreatment with F1:SnF1 ð80CL0310Ł\ HF ð75BSF814Ł\ HF:SbCl4 ð61GEP1018199Ł\ SbF2 ð44DOK"094#099Łor even better SbF2:SbCl4 ð47JGU1428Ł[ Mixed trihalomethyl ethers may be prepared by decreasingthe reaction temperature and the amount of HF "HF:SbCl2# used ð61GEP1018199\ 68JOC1896\ 75BSF814Ł[

Rico and Wakselman made mixed trihalomethyl ethers from potassium phenoxides\ CBr1F1 orCBrClF1 and a catalytic amount of 0!propanethiol kept in DMF at RT for 3 h[ Unfortunately\ lowyields "5Ð49)# were obtained with aryl di~uoromethyl ethers as the major and aryl bromo!di~uoromethyl ethers as the minor product ð70T3198Ł[

Synthesis of aryl trichloromethyl ethers from the corresponding nonhalogenated ether is achievedby photochlorination "69) yield# or by use of Cl1:PCl4 "60) yield# ð66CI"L#016\ 75BSF814Ł[

A carbonyl function can be regarded as a latent CF1 function[ The corresponding transformationis e}ected by SF3\ sometimes in the presence of HF[ Other reagents include the more easily handledalkylsulfur tri~uorides\ MoF5:BF2\ COF1 or the more reactive SeF3 ðB!81MI 596!90Ł[ According toHudlicky� ðB!81MI 596!90Ł the following order of reactivity is observed with SF3 as ~uorinating agent]alcohols×aldehydes\ ketones×acids\ amides×esters\ acid anhydrides×alkyl halides[

This has been exploited in the synthesis of tri~uoromethyl ethers[ Thus\ treatment of ~uoroformicacid esters "FC"1O#OR# with sulfur tetra~uoride leads to tri~uoromethyl ethers[ This reaction isespecially convenient for the synthesis of aryl tri~uoromethyl ethers\ and only when electron!withdrawing groups are present in the b!position can the aliphatic counterparts be synthesized insatisfactory yields ð50JA3759\ 53JOC0\ 53JOC00Ł[ Analogous to this O!alkyl chlorothioformic acidesters "ClC"1S#OR# can also be transformed to tri~uoromethyl ethers by treatment with MoF5\ in39Ð89) yield ð62TL1142Ł[ Trichloromethyl ethers are prepared similarly by chlorination with Cl1 ofZC"1S#OR "Z�Cl\ SMe# and ðROC"1S#SŁ1 ð44JA0788\ 45JA5969\ 47JGU1428\ 47ZOB1495\ 53ZOB0868\61JOC1540Ł[

A very mild method for the transformation of xanthates or "di~uoro"methylthio#methyl#ethers into tri~uoromethyl ethers was introduced by Kuroboshi et al[ They made use of "HF#8:pyridine:0\2!dibromo!4\4!dimethylhydantoin "DBH# as oxidative desulfurization!~uorinating agentand achieved yields of 37Ð79) ð81TL3062Ł[

Electrophilic addition of halogens to alkenes is a standard reaction in organic chemistry\ andaddition of trihalomethyl hypohalites\ which may be considered as a halogen bound to a super!halogen\ should therefore be expected to constitute a similar reaction\ which is exactly the case[ Thus\b!~uoro! or b!chloroalkyl tri~uoromethyl ethers may be prepared by addition of tri~uoromethylhypo~uorite or hypochlorite to alkenes[

The reaction of tri~uoromethyl hypochlorite with unsubstituted alkenes can be controlled attemperatures below −000>C\ whereas the reaction with electron!poor alkenes only proceeds at asigni_cantly higher temperature "½49>C#[ The addition is most probably polar in nature\ withMarkovnikov regiochemistry\ and gives syn!addition products[ Tri~uoromethyl hypo~uorite\ onthe other hand\ is more reactive and its reactions have to be conducted at much lower temperature[They are most probably of free!radical nature\ that is anti!Markovnikov and lack stereoselectivity[The yields are in most cases quantitative ð72JOC131\ 75IC265\ 80CL0310Ł[

Bis"tri~uoromethyl# and bis"trichloromethyl# ether are prepared from dimethyl ether by electro!~uorination "HF# ð49USP1499277Ł and photochlorination "Cl1# ð47CT404Ł\ respectively[

Tri~uoromethoxide is a rather poor nucleophile but\ with tris"dimethylamino#sulfonium""Me1N#2S¦^ TAS¦# as counterion\ nucleophilic substitution is possible[ Fluorination instead oftri~uoromethoxylation may\ however\ be expected at secondary substitution sites due to the elevatedreaction temperature required ð74JA3454\ 74MI 596!90Ł[

Transformation of an enol group into a di~uorohalomethoxy group has been accomplished byreaction with di~uorocarbene[ Thus\ 5!substituted 1!quinoxalones upon treatment with dibromo!di~uoromethane gave 5!substituted 1!"bromodi~uoromethoxy#quinoxalines[ Further treatment withpoly"hydrogen ~uoride#:pyridine yields the corresponding tri~uoromethyl ethers "Scheme 8#ð81JFC"48#306Ł[ A summary of selected methods for the synthesis of trihalomethyl ethers is found inTable 3[


R

NH

N

O

R

N

N

OCBrF2

R

N

N

OCF3

R

N

N

OCHF2

poly (HF)/pyridineCBr2F2

+

R = H, OMe, CF3, Cl

Scheme 9

Table 3 Selected methods for the formation of trihalomethyl ethers[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Startin` material Rea`ent"s# Reaction conditions Product"s# Ref["yield# ")#

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐAr0OH CCl3:HF 049>C\ 7 h Ar0OCF2 "09Ð62# 68JOC1896

R0OCCl2 HF:SbCl4 039>C\ R0OCF2 "64Ð75# 61GEP1018199R�aryl or alkyl

Ar0OMe Ar0OCCl2Cl1:hn 79>C\ "69# 66CI"L#016

Cl1:PCl4 089Ð199>C\ "60# 75BSF814

R0OC"1O#F SF3 099Ð064>C\ 5 h R0OCF2 53JOC0R�aryl or alkyl "07Ð61# 53JOC00

R0OC"1S#Z R0OCCl2Z�Cl\ SMe\ Cl1 9:49>Ca "14Ð89# "see text#SSC"1S#OR

R�aryl or alkyl MoF5 −14Ð029Ð089>C "39Ð89# 62TL1142

R0OC"1S#SMe Poly!HF:pyridine:DBHb −67Ð9>C\ 0 h R0OCF2 81TL3062R�aryl or alkyl "49Ð79#

CR11CR1 CF2OF varying CF2O0CR10CR10F 80CL0310CF2OCl CF2O0CR10CR10Cl 75IC265

"½quant[# 72JOC131

R0OTf CF2O−TAS¦c R0OCF2 ] R0F 74MI 596!90

R�alkyl "77\ 61 ] 17#d 74JA3454*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

a Depending on the actual compound type[ b DBH\ 0\2!dibromo!4\4!dimethylhydantoin[ c TAS¦\ tris"dimethylamino#sulfonium[ d Thisratio "tri~uoromethoxylation vs[ ~uorination# was achieved at a secondary site[ Milder conditions may be used at primary sites which favortri~uoromethoxylation[

"iii# Trihalomethyl esters\ CHal2OC"1O#R

Trihalomethyl esters may be considered as carboxylic acid superhalides and therefore expected tobe very reactive[ They may\ furthermore\ be expected to be thermally unstable and to releasecarbonyl dihalide with formation of the corresponding carboxylic acid halide\ as is the case withtrichloromethyl perhalobutanoic acid esters ð58CB2016Ł[

Only very few compounds containing a CHal2ZC"1Z?#R "Z\ Z?�O\ S\ Se\ Te# substructure areknown[ They are in general formed by halogenation of the corresponding methyl esters[ Thus\aerosol ~uorination of methyl per~uoroadamantaneacetate yields the tri~uoromethyl ester plus theacid ~uoride in 00) yield ð81JOC3638Ł and low yields were also obtained after electro~uorinationof methyl esters ð89JFC"49#062Ł\ whereas photochlorination of methyl perchloro!2!butenoate at RTgave the corresponding trichloromethyl ester in more than 82) yield ð58CB2016Ł\ and pho!tochlorination of dimethyl carbonate yields bis"trichloromethyl# carbonate in quantitative yieldð72HOU"E3#0257Ł[ Trichloromethyl esters are\ furthermore\ formed by the reaction between analcohol and diphosgene "CCl2C"1O#Cl# in 51Ð64) yield ð29JPR109\ 29JPR70Ł and obtained in71Ð80) yield by photochlorination of methyl chloroformate ð79OS"48#084Ł[ Bis"tri~uoromethyl#oxalate has been obtained in 80) yield by irradiation of a mixture of "CF2#1O1 and CO with a low!pressure Hg!lamp ð56MI 596!91\ 57MI 596!90Ł[ Other methods include thermal decomposition ofmethyl"tri~uoromethyl#dioxirane which yields tri~uoromethyl acetate "Equation "49## ð80JA6543Ł

120Three Halo`ens

and cleavage of amides with CF2OF at RT which gives N\N!dihaloamines and tri~uoromethyl esters"Scheme 09# ð63JCS"P0#621\ 79JFC"04#190Ł[

O

O

F3CMeCO2CF3 + F3CCO2Me

∆(50)

N

O

NO2

RR

RR

O2N CO2CF3

R1 NH

R2

O

R1 OCF3

O

R = H, Me

F3COCR2CR2NF2 +F3COF (excess)

F3COF+ F2NR2

Scheme 10

"iv# Trihalomethyl hypohalites\ CHal02OHal1

The ~uorinating agent tri~uoromethyl hypo~uorite may be prepared in good yields from COð37JA2875Ł\ CO1 ð55IS054Ł and COF1 ð58JA3321Ł by treatment with elemental ~uorine in the presenceof silver"II# ~uoride[ The hypo~uorite is quite thermostable and does not eliminate ~uorine unlessheated above 164>C[

Tri~uoromethyl hypochlorite is prepared in 88) yield from carbonyl ~uoride by treatment withchlorine mono~uoride:cesium ~uoride ð58JA1891Ł[

"v# O!Trihalomethyl peroxides\ CHal2OOR and trihalomethyl sulfonates\ CHal2OSO1R

Tri~uoromethyl hydroperoxide "CF2OOH# is prepared in 79) yield by hydrolysis of CF2OOCOFð60JA2771Ł or by thermal decomposition of 0!hydroxy!1\1\1!tri~uoro!0!"tri~uoromethyl#ethylhydroperoxide "0#\ which is prepared by oxidation of hexa~uoroacetone with 89) H1O1 ð60CC673Ł[Bis"tri~uoromethyl# peroxide is prepared in 81) yield from carbonyl ~uoride and chlorinetri~uoride "4 h at 149>C# ð54USP2191607Ł or tri~uoromethyl hypo~uorite ð46JA4517Ł[ Chloro tri!~uoromethyl peroxide adds to alkenes "−000>C:RT\ 1:26 h "depending on the alkene type## inanalogy with tri~uoromethyl hypochlorite^ b!chloroalkyl tri~uoromethyl peroxides are formed "09Ð64) yield# "Equation "40## ð64JA02Ł[

OHF3C

F3C O OH

(1)

F3COOCl +

R2

R1 R3

R4

–111 °C

R2

R1 R3

R4

ClF3COO

34–75%

(51)

Trichloromethyl hydroperoxide has also been prepared by photoperoxidation of trichloromethaneat RT "Equation "41## ð74AG37Ł[

(52)CHCl3O2, hν

20 °CCl3COOH

Acylation of tri~uoromethyl hydroperoxide is achieved by treatment with an acyl ~uoride underdry conditions[ Tri~uoroacetyl tri~uoromethyl peroxide has been prepared in this way "07 h\


RT# in 84) yield ð60JA2771Ł[ Acetyl trichloromethyl peroxide has been prepared similarly fromtrichloromethyl hydroperoxide and acetyl chloride ð74AG37Ł[

Tri~uoromethyl tri~uoromethanesulfonate may be prepared from the silver"I# sulfonate andtri~uoroiodomethane "199>C\ 13 h# in 75) yield ð68TL2754Ł or from tri~uoromethanesulfonylhypochlorite and tri~uorobromomethane "−000>C\ 0 h# in 84) yield ð79JA1570Ł[ Trichloromethyltri~uoromethanesulfonate has been prepared from mercury"II# tri~uoromethanesulfonate andbromotrichloromethane "9>C\ 01 h# in 67) yield ð58CB1049Ł[

"vi# N!Trihalomethoxy compounds\ CHal2ON"1O#nR

A general review of the synthesis of O!alkylated hydroxylamines has recently been given byAndree and Kluth ð89HOU"E05a#103\ 89HOU"E05a#160Ł[

O!"Tri~uoromethyl#di~uoroformaldehyde oxime has been prepared in excellent yield by de!hydro~uorination of CF2ONHCF2 with KF[ It is thermally stable at RT but dimerizes at RT in thepresence of CsF to CF2N"OCF2#CF1NOCF2 ð70JFC"07#330Ł[

Treatment of trichloromethyl hydroperoxide with N1O4:NaHCO2 at −14>C leads to trichloro!methyl pernitrate "CCl2COONO1# ð74AG37Ł[

"vii# Metal trihalomethoxides\ CHal2OM

Potassium tri~uoromethoxide may be prepared from carbonyl ~uoride and potassium ~uoride inacetonitrile at 19>C[ This salt is more stable than the corresponding alcohol and can be heated insolution to 79>C without formation of carbonyl ~uoride ð54CJC0782Ł[

5[96[1[0[1 Three halogens and a sulfur function

"i# Trihalomethanethiols\ CHal2SH

Tri~uoromethanethiol is a stable compound whereas the other trihalomethanethiols may beexpected to be rather unstable ð72HOU"E3#514\ 82TL1862Ł[ The former has been prepared from mer!cury"II# tri~uoromethanethiolate in 88) yield by treatment with hydrogen chloride ð42JCS2108Ł orin 89) yield by treating "tri~uoromethylthio#silane with hydrogen iodide ð59JCS2405Ł[ The synthesisof trichloromethanethiol has previously been claimed by Connolly and Dyson ð23JCS711Ł\ but arecent investigation showed this to be in error ð82TL1862Ł[

"ii# Trihalomethyl sul_des\ CHal2SR

The synthesis of sul_des has previously been reviewed by Gundermann and Hu�mkeð74HOU"E00#047Ł[

Photochlorination of aryl methyl sul_des leads to aryl trichloromethyl sul_des which may betransformed to the corresponding tri~uoromethyl analogues by treatment with SbF2 ð26FRP719684\27BRP368663\ 41ZOB1105\ 43JGU774\ 59JOC59Ł[ In the presence of electron!withdrawing groups in thearomatic moiety BF2 catalysis and higher reaction temperatures are required for the ~uorinationstep ð64S610Ł[

Aryl tri~uoromethyl sul_des have\ furthermore\ been prepared from the corresponding arylhalides by direct tri~uoromethylthiolation with methyl ~uorosulfonyldi~uoroacetate "FSO1CF1!CO1Me#\ CuI and S7[ The choice of solvent and of aryl halide as well as of the metal iodide isof great importance[ Yields ranging from 30) to 63) have been reported in HMPA and N!methylpyrrolidone whereas no reaction is observed in DMF[ Aryl iodides were found to be mostreactive and aryl chlorides inactive ð82CC807Ł[ Replacement of CuI by KI results in the formationof tri~uoromethane after work!up ð78CC694Ł[

Replacement of aryl bound halogen by a tri~uoromethylthio group can also be accomplishedwith di}erent soft metal tri~uoromethanethiolates\ CF2SM\ M being Cu"I#\ Ag"I# or Hg"II#[

Thus\ CF2SCu "74Ð029>C\ 0[4Ð5 h in DMF\ HMPA or N!methylpyrrolidone#\ tri~uoro!methanethiolates aryl iodides in yields of approximately 64) ð74S556Ł[ This method is also

122Three Halo`ens

available for the synthesis of tri~uoromethylthio substituted heteroaromatics\ and the best yieldsare achieved with electron!poor systems ð64S610Ł[ Yields may\ furthermore\ be improved by use ofcopper"I# tri~uoromethanethiolate on alumina support ð89JFC"37#138Ł[

Mercury"II# bis"tri~uoromethanethiolate#\ "CF2S#1Hg\ reacts with alkyl and allyl chlorides withformation of the corresponding tri~uoromethyl sul_des ð48JA2464\ 56JOC1952\ 70TL2936Ł[

Silver"I# tri~uoromethanethiolate\ CF2SAg\ reacts with alkyl halides under formation of alkyltri~uoromethyl sul_des with an insoluble silver halide as a convenient by!product ð50JCS1486\54ZOB0517Ł[

Other sources of tri~uoromethanethiolate ions which have been used in nucleophilic aromaticsubstitution include the in situ formation of tri~uoromethanethiolate from thiocarbonyl ~uoride orbis"tri~uoromethyl# trithiocarbonate ""CF2S#1C1S# and calcium\ potassium or caesium ~uorideð41JCS1087\ 74C074\ 76JCS"P0#1008\ 77JCS"P0#0068Ł[

Electron!rich aromatic systems undergo substitution with tri~uoromethanesulfenyl chlorideð49JA2418\ 42CB446\ 53JOC787\ 66CB56\ 67JFC"00#498Ł and trichloromethanesulfenyl chloride ð52ACS1469Ł\in some cases under free radical conditions\ yielding aryl tri~uoromethyl sul_des in good yields"generally in excess of 59)# and aryl trichloromethyl sul_des\ respectively[ Tri~uoromethanesulfenylchloride as well as tri~uoromethanesulfenyl ~uoride reacts with nucleophiles^ with alkenes theyform b!halo"tri~uoromethylthio#alkanes ð51JA2037\ 56JOC1952\ 76JFC"23#364Ł\ and with aryl Grignardreagents\ tri~uoromethanesulfenyl chloride "at 9>C# forms aryl tri~uoromethyl sul_des\ which are\however\ contaminated with the corresponding aryl chlorides ð53JOC784Ł[ Tri~uoromethanethiolalso reacts with alkenes under UV irradiation with formation of the corresponding alkyl tri!~uoromethyl sul_des ð50JA739Ł[

Aromatic potassium thiolates react with bromotri~uoromethane under pressure "1Ð2 atm\ RT\DMF# to give the corresponding tri~uoromethyl sul_des "6Ð64) yield# ð73CC682\ 74JOC3936Ł[ Theuse of mixed tetrahalomethanes such as dibromodi~uoromethane or bromochlorodi~uoromethaneleads to mixed halomethyl sul_des ð70TL0886\ 70TL212Ł[

Alkylation of aliphatic and aromatic disul_des may be conducted in DMF:H1O at RT underradical conditions by treatment of bromotri~uoromethane with sulfur dioxide radical anion "derivedfrom Na1S1O3:NaO1SCH1OH# and Na1HPO3 to neutralize the sulfur dioxide formed during thereaction "20Ð82) yield# ð80CC882Ł[ Tri~uoroiodomethane reacts similarly with sul_des under UVirradiation\ but more slowly\ for example\ the reaction with dimethyl sul_de "hn\ 10 days# gives a81) yield of tri~uoromethyl methyl sul_de ð61JCS"P0#1079Ł[ This reaction has been extended toalkane!\ arene! and heteroarenethiols as well ð68ZOR285\ 68ZOR0134Ł and may\ furthermore\ beconducted under phase transfer conditions "41Ð74) yield# ð71JFC"10#254Ł[

N!"Tri~uoromethyl#!N!nitrosobenzenesulfonamide "CF2N"NO#SO1Ph\ TNS!B#\ N!"tri~uoro!methyl#!N!nitrosotri~uoromethanesulfonamide "CF2N"NO#SO1CF2\ TNS!Tf#\ S!"tri~uoromethyl#!dibenzothiophenium tri~ate "TBT!Tf# and its seleno analogue "TBSe!Tf# "1#\ and "3!chlorophenyl#!"1\5!dimethylphenyl#tri~uoromethylsulfonium hexa~uoroantimonate "2# have been developed ase.cient tri~uoromethylating agents and are more easily handled than tri~uoroiodomethane gas[Thus\ TNS!B reacts with dialkyl sul_des to give the corresponding tri~uoromethyl alkyl sul_des in44Ð53) yield ð71TL2818Ł[ TNS!Tf gives generally higher yields of tri~uoromethyl sul_des fromthiols and dialkyl sul_des after shorter reaction times ð75BCJ336Ł[ The reaction of sodium alkane!thiolates with "1# ð89TL2468Ł produces the corresponding tri~uoromethyl sul_des in 36Ð76) yield\as does treatment with "2# ð73ZOR004Ł[

(2)

Z

CF3

+

TfO–

Z = S, Se, Te

Cl

S

CF3

(3)

+

SbF6–

Direct chlorination of methyl sul_des leads to trichloromethyl sul_des in yields ranging from45Ð099)\ as does chlorination of alkyl halodithioformates a reaction which also may be used forthe formation of dichlorohalomethyl sul_des ð28AG346\ 48ZOB2675\ 59ACS1129\ 51ACS006Ł[

Trichloromethyl sul_des have\ furthermore\ been prepared in 59Ð65) yield from thiocyanates bytreatment with trichloromethyl anions "derived from CHCl2:NaOH# under phase transfer conditionsð63S163Ł[

Finally\ trihalomethyl sul_des can be interconverted] CF2SR:CCl2SR "with AlCl2#^ CF2SR:


CBr2SR "with BBr2 or AlBr2#^ CCl2SR:CF2SR "with KF:07!crown!5\ SbF2 or HF#^ CCl2SR:CBr2SR "with HBr#[ Other ~uorinating agents include AgBF3\ Hg1F1 and ðBnNMe2Ł¦F−

ð27USP1097595\ 41JA2483\ 45CB0059\ 56ZOB0669\ 60GEP1992032\ 66JOC1913\ 70TL0886Ł[Kolomeitsev et al[ have developed a method for the synthesis of tri~uoromethyl sul_des from the

corresponding alcohols[ The alcohol is treated with bis"diethylamino# chloro phosphite which givesthe intermediate diethylamino alkyl phosphite "ROP"NEt1#1# in 79Ð89) yield[ Further treatmentwith bis"tri~uoromethyl# disul_de gives the tri~uoromethyl alkyl sul_de in 89Ð84) yield[ The overallyields in this two step procedure are excellent "61Ð75)# ð83S034Ł[ Table 4 presents a summary ofselected methods for the formation of trihalomethyl sul_des[

Table 4 Selected methods for the formation of trihalomethyl sul_des[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Startin` material Rea`ent"s# Reaction Product Ref[conditions "yield# ")#

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐAr0SMe Cl1\ hn Ar0SCCl2 "45Ð099# "see text#

R0SC"1S#X R�aryl Cl1 ½39>C\ R0SCCl2 "04Ð79# 48ZOB2675or alkyl X�Cl\ F

Ar0X\ X�Br or I FSO1CF1CO1Me\ S7\ CuI 099Ð019>C\ 4Ð7 h Ar0SCF2 "30Ð63# 82CC807\Ar�Ph or 78CC694

heteroaromatics

Ar0I\ Ar�Ph or CF2YCu Y�S\ Se 74Ð029>C\ 4Ð5 h Ar0SCF2 "30Ð84# 89JFC"37#138\pyridine 74S556\ 64S610

ArH\ ArH�elec[ rich CF2SCl\ Lewis cat[ 59>C\ 19 h Ar0SCF2 "39Ð67# "see text#aromatics

R1C1CR1 CF2SCl\ hn CF2S0CR1CR10Cl 56JOC1952\"40Ð72# 51JA2037

Ar0MgX CF2SCl 9>C Ar0SCF2 "½49)# 53JOC784

R1C1CR1 CF2SH\ hn CF2S0CR1CR10H 50JA739"45Ð71#

Ar0SK CF2Br 1Ð2 atm\ RT\ 2 h Ar0SCF2 "6Ð64# 74JOC3936\73CC682

R0SNa "1# or "2# R0SCF2 "36Ð76# 89TL2468\73ZOR004

R1S TNS!B or TNS!Tfa R0SCF2 "44Ð53# 75BCJ336\71TL2818

R1S\ R�aryl or alkyl CF2Br\ Na1S1O3\ RT R0SCF2 80CC882NaO1SCH1OH\

Na1HPO3

Ph0SCCl2 SbF2\ "BF2# Ph0SCF2 "69# "see text#

R0SCX2\ X�F\ Cl\ Br "see text# R0SCY2 Y�F\ Cl\ "see text#Br

R0OH\ R�alkyl i\ "Et1N#1PCl:NEt2^ i\ −39>C\ 1 h^ R0SCF2 83S034or benzyl ii\ CF2SSCF2 ii\ −49Ð19>C\ 4 min[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐa N!"Tri~uoromethyl#!N!nitrosobenzenesulfonamide "CF2N"NO#SO1Ph\ TNS!B#\ N!"tri~uoromethyl#!N!nitrosotri~uoromethanesulfon!

amide "CF2N"NO#SO1CF2\ TNS!Tf#[

"iii# Trihalomethyl sulfoxides and trihalomethyl sulfones\ CHal2S"1O#nR

The synthesis of sulfoxides and sulfones has previously been reviewed by Gundermann andHu�mke ð74HOU"E00#554Ł and by Schank ð74HOU"E00#0018Ł[

Partial oxidation of alkyl:aryl tri~uoromethyl sul_des with 16) hydrogen peroxide in acetic acid"1 h re~ux# yields the corresponding sulfoxides ð54ZOB0517Ł[ More drastic oxidation with nitric acid\hydrogen peroxide or chromium trioxide in glacial acetic acid gives the corresponding sulfonesð41JA2483\ 54ZOB0517\ 56JOC1952\ 76JCS"P0#1008\ 82CC807Ł[

The transfer of CX2SO1 groups is possible by reactions of nucleophiles such as BuLi withelectrophilic species like "CF2SO1#1O\ "CF2SO1#1NPh and CF2SO1Cl[ In the case of primary or

124Three Halo`ens

secondary organometallics ditri~ation is possible due to the presence of acidic a!protons in themonotri~ated products ð66JOC2764Ł[ Alkynyl tri~uoromethyl sulfones have been prepared fromsodium alkynides and tri~ic anhydride in 06Ð64) yield ð81T078Ł[

Monotri~ation of aromatic compounds can be carried out as FriedelÐCrafts tri~ation with"CF2SO1#1O:AlCl2\ but only aromatic compounds of at least intermediate reactivity such as xylene\toluene\ and benzene are tri~ated ð66JOC2764Ł[

Aryl tri~uoromethyl sulfones have been prepared in high yields "69Ð88)# by di~uorocarbeneinsertion into arenesulfonyl ~uorides[ The reagent mixture used is Me2SiCF2 or Me2SnCF2 and"Me1N#2S¦Me2SiF1

−"TASF#[ The yield is una}ected by electronic e}ects of arene substituents"Equation "42## ð89S0040Ł[

(53)ArSO2F2Me3MCF3, TASF

THF, 20 °CArSO2CF2F

TASF = (Me2N)3S+ Me3SiF2–

M = Sn, Si

70–99%

Transformation of an arenesulfonamide into an N!"tri~uoromethyl#azosulfonylarene is e}ectedby treatment of the amide with tri~uoronitrosomethane in base "70Ð81) yield#[ This intermediateeliminates N1 on heating to form the corresponding tri~uoromethyl phenyl sulfone "½39) yield#"Scheme 00# ð71CL0408Ł[

baseF3CNO + H2NSO2Ar

∆

–N2

F3CSO2Ar

81–92% ~40%Scheme 11

F3CN=NSO2Ar

"iv# S!Trihalomethyl thio! and dithioesters\ CHal2SC"1Z#R "Z�O or S#

Tri~uoromethyl thioesters have been prepared by the reaction of mercury"II# bis"tri~uoro!methanethiolate#\ "CF2S#1Hg\ with acyl chlorides "39Ð49>C\ 12Ð40) yield# ð48JA2464Ł[ Bis"tri!~uoromethyl# trithiocarbonate is formed in ½099) yield by CsF treatment at 9>C of thiocarbonyldi~uoride ð55AG895\ 57CB1598Ł[

FriedelÐCrafts "tri~uoromethyl#thiothioacylations have been achieved with HF:SbF4 andFC"1S#SCF2 ð76CB318Ł with the latter formed from thiocarbonyl ~uoride and potassium ~uorideð57CB1598Ł "Scheme 01#[The corresponding "trichloromethyl#thiothioacylation "69>C\ 3 h^ RT 05 h#has been achieved in 15) yield by treating anthracene with trichloromethyl chlorodithioformateformed in 64) yield from trichloromethanesulfenyl chloride and CS ð73JOC2743Ł[ Condensation ofbis"tri~uoromethyl# trithiocarbonate ""CF2S#1C1S# with "CF2S#1C1C"SCF2#1 in the presence ofa catalytic amount of HgCl1 "2 d at 069>C# gives 0\0!bis"tri~uoromethylthio#!1\1!bisð"tri~uoro!methylthio#thiocarbonylŁethene in 09) yield\ with bis"tri~uoromethyl# disul_de as the main productð66CB805Ł[

S

FF

S

SCF3F

S

SCF3F3CS

Scheme 12

+ MF (SCF2)x + +

M = K 3 1 –20–0 °C, 1 h

HF/SbF5 +S

SCF3F

10–15%M = Cs

58%

R

1

Et2O–50 °C–RT

SCF3

S

R

100%–78 °C, 18 h1

RH4-MeO3-CF32,5-F2

Yield (%)65542735


"v# Trihalomethanesulfenyl\ !sul_nyl and !sulfonyl halides^ CHal02S"1O#n"Hal1#

The synthesis of sulfenyl\ sul_nyl and sulfonyl halides has previously been reviewed by Schubartð74HOU"E00#52Ł\ Krauthausen ð74HOU"E00#503Ł and Pawlenko ð74HOU"E00#0956Ł[ See also the reviewby Sizov et al[ on the formation of poly~uoroalkanesulfenyl chlorides ð81RCR406Ł[ In this sectiononly sulfenyl halides are treated\ due to their synthetic importance in the synthesis of trihalomethylsul_des[

Umpolun` of metal trihalomethanethiolates can be achieved by chlorination to the correspondingtrihalomethanesulfenyl chlorides ð50JCS1486Ł[ Bromine and iodine\ however\ oxidize silver"I# tri!~uoromethanethiolate to bis"tri~uoromethyl# disul_de ð50JCS1486Ł[

The industrial preparation of trichloromethanesulfenyl chloride takes place by chlorination ofcarbon disul_de under conditions which suppress the formation of bis"trichloromethyl# disul_deð60S367\ 55FRP0326897Ł[

A general method for the synthesis of trihalomethanesulfenyl halides is to halogenate "Hal1#thiocarbonyl halides and this method can therefore also be used to prepare mixed tri!halomethanesulfenyl halides ð48ZOB2681\ 51JCS3250\ 53AG796\ 65CB2321Ł^ furthermore\ by halogenexchange in trihalomethanesulfenyl halides with SbF2:SbCl4 "Br:F#\ HF "Cl:F#\ NaF "Cl:F#\HF:CrOF "Cl:F# or HBr "Cl:Br# ð47USP1710443\ 48ZOB2390\ 48ZOB2673\ 59JOC1905\ 56GEP0121843Ł[

Still other methods include chlorination of disul_des\ for example chlorination of dimethyldisul_de leads to trichloromethanesulfenyl chloride in 79) yield and high purity while photo!chlorination at RT of bis"tri~uoromethyl# disul_de leads to tri~uoromethanesulfenyl chloride in44) yield ð42JCS2108\ 50USP2903960Ł[

"vi# Trihalomethanesulfenic\ !sul_nic and !sulfonic derivatives^ CHal2S"1O#nZR

The trihalomethanesulfenyl\ !sul_nyl\ and !sulfonyl halides are important starting materials forthe synthesis of other trihalomethanesulfenyl\ !sul_nyl\ and sulfonyl derivatives[ For examplemercury"II# bis"tri~uoromethanethiolate# ð"CF2S#1HgŁ\ reacts with sulfenyl chlorides with formationof the corresponding tri~uoromethyl disul_des ð48JA2464Ł[ Other methods which allow the formationof mixed trihalomethyl disul_des are the photoreaction between thiocarbonyl halides and trihalo!methanesulfenyl halides ð57CB1506Ł and the photoreductive dimerization of trihalomethanesulfenylchlorides with\ for example\ CO as reductant ð56JINC1708Ł[

Trihalomethanesulfenic acids are\ as most other sulfenic acids\ unstable[ Trichloro!methanesulfenic acid for instance eliminates HCl with formation of dichlorosul_ne "Cl1C1S1O#ð58CC767Ł\ whereas the sul_nic and sulfonic acids are stable compounds[

A preparative method which gives access to halodi~uoromethanesulfonic acid derivatives in highyields is the decarbonylative photolysis of HalC"1O#CF1SO1F "the reaction is conducted at79Ð89>C for Hal�Cl\ 49>C for Hal�Br\ RT for Hal�I# ð68S861Ł[

The synthesis of sulfenic\ sul_nic and sulfonic acid derivatives has been reviewed previously bySchubart ð74HOU"E00#52Ł\ Krauthausen ð74HOU503Ł\ Pawlenko ð74HOU"E00#0944\ 74HOU"E00#0973Łand Ja�ger ð74HOU"E00#0962Ł and is not discussed here[ See\ however\ the review by Sizov et al[ ontransformation of poly~uoroalkanesulfenyl chlorides ð81RCR406Ł[

The CF2SO1 group "in CF2SO1Ar# was found by NMR measurements to be even more electron!attracting than the NMe2 group "in ArNMe2

¦# ð57ZOB1480Ł[

"vii# Metal trihalomethanethiolates^ CHal2SM

Metal trihalomethanethiolates are important as precursors of aryl trihalomethyl sul_des "videsupra# and their synthesis is therefore mentioned here[

Copper"I# tri~uoromethanethiolate\ CF2SCu\ is obtained in nearly quantitative yield by heating"49Ð59>C# CF2SSCF2 with copper powder in DMF\ HMPA or N!methylpyrrolidone for 0Ð2 h\depending on the activity of the copper powder ð74S556Ł[ The thiolate can be used in situ\ but alsoisolated and stored until needed[ The copper"I# thiolate can also be prepared by reaction ofmercury"II# bis"tri~uoromethanethiolate# with copper powder ð48JA2464Ł or by reaction of AgSCF2

with Cu:CuBr ð74S556Ł[Mercury"II# bis"tri~uoromethanethiolate#\ "CF2S#1Hg\ may be prepared from HgF1 and carbon

disul_de in 61) yield after heating 3 h at 149>C in a steel autoclave ð48JA2464Ł or photochemicallyin 89) yield from bis"tri~uoromethyl# disul_de and metallic mercury ð42JCS2108Ł[

126Three Halo`ens

Silver"I# tri~uoromethanethiolate\ CF2SAg\ is formed in 68) yield by the reaction of dry silver"I#~uoride with dry carbon disul_de after heating 01 h at 039>C in a steel autoclave ð50JCS1486Ł^ itreacts with alkyl halides with formation of alkyl tri~uoromethyl sul_des and an insoluble silverhalide as a convenient by!product ð50JCS1486\ 54ZOB0517Ł[

5[96[1[0[2 Three halogens and a Se or Te function

"i# Tri~uoromethylselenium compounds^ CF2SeR

The chemistry of tri~uoromethylselenium compounds has been reviewed and compared with thatof the corresponding sulfur compounds ð75JFC"21#304Ł[

Aryl tri~uoromethyl selenides can be prepared from aryl halides and "CF2#SeCu in analogy withthe synthesis of the corresponding tri~uoromethyl sul_des "Equation "43## ð74S556Ł[ Se!"Tri!~uoromethyl#dibenzoselenophenium tri~uoromethanesulfonate "1^ Z�Se# can be obtained by ~uo!rination of a mixture of 1!ð"tri~uoromethyl#selenoŁbiphenyl with CF2SO2H and by treatment ofthe corresponding sulfoxide with "CF2SO1#1O[ Compound "1# can be used as an electrophilictri~uoromethylation reagent "vide supra# ð82JA1045Ł[ Bis"tri~uoromethylseleno#ketene is available bydehydration of bis"tri~uoromethylseleno#acetic acid or by dehydrochlorination of the correspondingacid chloride ð81CB460Ł[

Z I

X

Z YCF3

X (54)+ CuI+ F3CYCu

85–130 °C1.5–6 h

41–95%

X = H, Me, NO2; Y = S, Se; Z = CH, N

Mercury"II# tri~uoromethaneselenolate reacts with S!tri~uoromethyl bromothioformateð"CF2#SC"1O#BrŁ "029>C for 05 h# with formation of "CF2S#C"1O#Se"CF2# ð67CB1780Ł[ Runovernight at 9>C the same reaction gives a yield of 75) ð65CB2321Ł[

Oxidation of an aryl tri~uoromethyl selenide with chlorine yields the corresponding aryl!dichloro"tri~uoromethyl#selenane\ ArSeCl1"CF2# ð74S556Ł[ Aryl tri~uoromethyl selenides can beoxidized with chlorine:water to the corresponding selenoxides and with tri~uoroperacetic acid tothe corresponding selenones ð57ZOB1498Ł[ Tri~uoromethaneselenonic acid\ CF2SeO2H was preparedfor the _rst time by Haas and Weiler in 0874 by oxidation of CF2SeO1H with KMnO3 under neutralaqueous conditions[ Upon attempted puri_cation it decomposes "at concentrations higher than89)# to CF3\ COF1\ SeO1 and H1O ð74CB832Ł[

"ii# Tri~uoromethyltellurium compounds^ CF2TeR

Mixtures of bis"tri~uoromethyl# telluride and dialkyl tellurides are subject to ligand exchangeand form alkyl tri~uoromethyl tellurides such as BnTe"CF2# and ButTe"CF2# ð81C67\ 81OM1836Ł[Mixtures of "CF2#1Te and "C5F4#1Te as well as of "CF2#1Te1 and "C5F4#1Te1 undergo scramblingunder irradiation to give "CF2#Te"C5F4# and "CF2#TeTe"C5F4#\ respectively ð89JFC"37#196\ 82CM0210Ł[An 75) yield of dimethyl"tri~uoromethyl#telluronium iodide is obtained in the photoreaction"at −67>C# of Me1Te and CF2I ð78ZAAC"465#114Ł[ Te!"Tri~uoromethyl#dibenzotelluropheniumtri~uoromethanesulfonate "1^ Z�Te# can be obtained by treatment of 1!ð"tri~uoromethyl#telluroŁbiphenyl with "CF2SO1#1O and DMSO[ Compound "1# can be used as an electrophilictri~uoromethylation reagent ð82JA1045Ł[ Tetrakis"tri~uoromethyl#tellurane "CF2#3Te\ which hasbeen obtained from dichlorobis"tri~uoromethyl#tellurane and "CF2#1Cd\ reacts with ~uorideions to form ð"CF2#3TeFŁ−\ with ~uoride ion acceptors to form ð"CF2#2TeŁ¦\ and with XeF1 to formthe hypervalent tellurium compound "CF2#3TeF1 ð81ZAAC"597#58Ł[

5[96[1[1 Three Halogens and a Group 04 Element

5[96[1[1[0 Three halogens and a nitrogen function

This subject has previously been reviewed by Marhold ð72HOU"E3#514Ł[


"i# Trihalomethylamines\ CHal2NR1

The unsubstituted and monosubstituted trihalomethylamines possess more or less salt characterand are quite unstable[ The phosgeneiminium character makes them prone to hydrolysis "Equation"44##[

NH2

X

X

X NH2+ X–

X

X

(55)

"a# Primary trihalomethylamines\ CHal2NH1[ Tri~uoromethylamine has been prepared by treat!ing N\N!dichloro!N!"tri~uoromethyl#amine with HCl at −67>C which gives the hydrochloride[The free base is stable below ½−29>C\ above which it eliminates HF with formation of di~uoro!phosgeneimine "Scheme 02# ð68JA236Ł[ Synthesis of trichloromethylamine is achieved by treatingClCN with HCl[ The intermediate hydrochloride is unstable\ but addition of antimony"V# chlorideconverts it into the stable hexachloroantimonate salt ð53CB0175\ 62BSB12Ł[

F3CNCl2 + 3HCl–Cl2 amine base

F3CNH3+ Cl– F3CNH2

Scheme 13

"b# Secondary trihalomethylamines\ CHal2NHR[ Secondary tri~uoromethylamines have beenprepared from N!substituted isocyanide dichlorides "CCl11NR# by reaction with HF[ Yields of58Ð87) have been achieved with N!aryl substituted compounds\ whereas the aliphatic counterpartsdimerize and:or polymerize "Equation "45## ð52BEP521254Ł[ Bis"tri~uoromethyl#amine may be syn!thesized by addition of HF to tri~uoromethyl isocyanide di~uoride "CF2N1CF1# in 78) yieldð48ZOB1048Ł or by HF treatment of trichloromethyl isocyanide dichloride in 34) yield ð44JCS1421\47JA2593Ł[

HFF3CNHRN

Cl

Cl R

R = aryl 69–98%

(56)

"c# Tertiary trihalomethylamines\ CHal2NR1[ Tertiary tri~uoromethylamines are stable com!pounds which have been prepared by ~uorination of R1NC"1S#SSC"1S#NR1 with either SF3 orCOF1\ or by ~uorination of N\N!disubstituted ~uorothioformamides "FC"1S#NR1# with SF3[ Thesemethods may be applied to both aryl and alkyl tri~uoromethylamines "Equation "46## ð50JA2311\51JA3164\ 60ZOR1999Ł[

R2NCF3

58–73%R2N S

S NR2

S

S

SF4(57)

Tertiary trichloromethylamines have been made similarly by chlorination of N\N!disubstitutedchlorothioformamides with Cl1 or PCl4 "½65) yield# ð48ZOB2675\ 60ZOR1973Ł\ by chlorination ofR1NC"1S#SC"1S#NR1 with COCl1 "82) for R�Me# ð72HOU"E3#514Ł\ by chlorination of N\N!diarylthioformamides "HC"1S#NAr1# and of alkanesulfonylthioformamides "RSO1C"1S#NR1#ð71GEP2933105\ 61CB1743Ł[ N!"1\3\5!Trichlorophenyl#!N\N!bis"trichloromethyl#amine has been pre!pared by chlorination at 039>C of the corresponding N\N!dimethylamine ð58LA"629#039Ł[ Alkylationof N!substituted phosgeneimines with strong alkylating agents such as RO2SF\ followed byCl−:FSO2

−!anion exchange\ gives the corresponding dichlorophosgeneiminium chloridesð62AG726Ł[ Dimethyl"tribromomethyl#amine has been prepared similarly to the trichloromethyl andtri~uoromethyl analogues\ for example\ by bromination with Br1 of Me1NC"1S#SS"C1S#NMe1

ð61LA"644#034Ł[Tertiary tri~uoromethylamines may alternatively be synthesized from the corresponding tri!

chloromethylamines by treatment with HF or SbF2 under anhydrous conditions in 47Ð68) yieldð55ZOB0298\ 71GEP2933105Ł[

Bis"tri~uoromethyl#alkylamines are formed by alkylation of metal "K¦\ Cs¦\ Hg1¦# bis"tri!~uoromethyl#amides in 33Ð73) yield ð79JCS"P0#1143\ 64IZV1168Ł[

N!Bromo! and N!iodo!N\N!bis"tri~uoromethyl#amines add to double bonds with formation

128Three Halo`ens

of b!bromo! and b!iodoalkyl bis"tri~uoromethyl#amines\ respectively\ in 61Ð87) yield ð47JA2593\54JCS5030\ 57JCS"C#685\ 79JCS"P0#0433Ł[

Tris"tri~uoromethyl#amine has been prepared by treatment of tri~uoromethyl isocyanide di!~uoride with CF2SF4 ð46JA58Ł and as a by!product "11) yield# of the reaction between O\N\N!tris"tri~uoromethyl#hydroxylamine and tri~uoromethyl isocyanide di~uoride where N\N\N?\N?!tetrakis"tri~uoromethyl#hydrazine is the main product ð56JCS"C#0130Ł[

Mixed N\N!dihalo"trihalomethyl#amines "halo equals chlorine or ~uorine# have been prepared in59Ð64) yield from the corresponding imines by treatment "−19>C for 2Ð3 h# with chlorinemono~uoride ð60IC0524Ł[

"ii# N!Trihalomethylamides\ CHal2NRC"1O#R

Isocyanates are used as starting materials for the synthesis of N!alkyl!N!"tri~uoromethyl#!carbamoyl ~uorides and of O!alkyl!N!"tri~uoromethyl#carbamates[ Thus\ tri~uoromethyl iso!cyanate reacts with CsF and subsequently with an alkyl halide\ with formation of N!alkyl!N!"tri~uoromethyl#carbamoyl ~uorides "Scheme 03# ð65IZV198Ł while the reaction of tri~uoromethylisocyanate with alcohols yields O!alkyl!N!"tri~uoromethyl#carbamates in 55Ð73) yield "Equation"47## ð48ZOB1046Ł[ Aryl isothiocyanates are converted into N!aryl!N!"tri~uoromethyl#carbamoyl~uorides in 32Ð72) yield by treatment with HgF1\ followed by COF1:CsF "Equation "48##ð54JA3227Ł[

CsF RBrF3CN • O O

F

NCF3–Cs+

F

O NCF3

RScheme 14

(58)F3CN • O + ROH

O

NH

ORF3C

66–84%

i, HgF2ii, COF2/CsF

N • S

R

N

R

CF3O

F

(59)

43–83%

Hydrolysis of N\N!bis"tri~uoromethyl#carbodiimide gives N\N?!bis"tri~uoromethyl#ureað56JCS"C#1291Ł[

"iii# Trihalomethyl isocyanates\ CHal2N1C1O^ trihalomethyl isocyanide dihalides\CHal2N1CHal1 and N!"trihalomethyl#carbodiimides CHal2N1C1NR

Key starting materials in the synthesis of bis"tri~uoromethyl#amines are\ as mentioned above\tri~uoromethyl isocyanide di~uoride "CF2N1CF1# and trichloromethyl isocyanide dichloride"CCl2N1CCl1#[ One high yielding method for the synthesis of these is the chlorination of N\N!dimethylcarbamoyl chloride which gives trichloromethyl isocyanide dichloride in 76) yieldð52GEP0111806\ 69GEP0815548Ł^ further treatment with sodium ~uoride yields tri~uoromethyl iso!


cyanide di~uoride which distills o} from the reaction mixture "67) yield\ Scheme 04#ð61CA"66#014841Ł[ Other methods of preparation of these compounds are described in Section 5[19[0[

N

Me

Me O

Cl

N

Cl3C Cl

Cl

N

F3C F

F

Cl2

250–300 °C

NaF

150 °C

87% 78%

Scheme 15

Other key starting materials in the synthesis of "trihalomethyl#amines are the trihalomethylisocyanates "CHal2N1C1O#[ Tri~uoromethyl isocyanate is formed in 64) yield from tri!~uoroacetyl chloride by treatment with azidotrimethylsilane and thermolysis of the intermediarytri~uoroacetyl azide by Curtius amide degradation "Scheme 05# ð68CB1047Ł[ Tri~uoromethyl iso!thiocyanate is formed in 59) yield upon H1S treatment of tri~uoromethyl isocyanide di~uoride\followed by distillation from NaF ð58ZOB088Ł[ Trichloromethyl isocyanate is unstable andrearranges quantitatively to chloroformyl isocyanide dichloride[ The same product is obtained in78) yield by photochlorination of methyl isocyanate "Scheme 05# ð65CA"74#031557Ł[ Tribromomethylisocyanate is formed in 58) yield by NBS bromination of methyl isocyanate "Scheme 05# ð71CB759Ł[

N!"Tri~uoromethyl#carbodiimides are formed in 35Ð79) yield by the reaction between tri!~uoromethyl isocyanide di~uoride and an alkyl! or arylamine in the presence of KF:Et2Nð79JFC"04#058Ł[

F3C

O

Cl F3C

O

N3

F3CN • O

MeN • O Cl3CN • ON

Cl

Cl

O

Cl

MeN • O

NBS16 h

69%

N

Br

Br

O

Br

TMS-N3autoclave

20 °C, 2 h

hν, Cl2autoclave

70 °C, 15 h89%

∆, –N2

60 °C, 12 h

Scheme 16

75%

Br3CN • O

"iv# N!Halo"trihalomethyl#amines\ CHal02NRHal1

N!Bromo! and N!iodo!N\N!bis"tri~uoromethyl#amine are to be considered as umpoled aminesand thus as key intermediates for the introduction of the bis"tri~uoromethyl#amine functionality byreaction with nucleophiles such as alkenes "vide supra#[ They are formed by bromination andiodination of mercury"II# bis"tri~uoromethyl#amide in 89) and 56) yield\ respectively ð47JA2593\55JCS"A#256Ł[ N!Chloro!N\N!bis"tri~uoromethyl#amine is similarly formed in 69) yield by chlori!nation of potassium bis"tri~uoromethyl#amide and N!~uoro!N\N!bis"tri~uoromethyl#amine isobtained by ~uorination of tri~uoromethyl isocyanide di~uoride with elemental ~uorineð70JFC"06#352Ł[

Addition of halogen to N!halo isocyanide dihalides "Hal1C1NHal# or cyanogen chloride leadsto N\N!dihalo!N!"trihalomethyl#amines in 59Ð86) yield ð69CC284\ 61LA"644#034\ 70JFC"06#352Ł[

"v# N!"Trihalomethyl#hydroxylamines\ CHal2NR0OR1^ trihalonitrosomethanes\ CHal2NO andtrihalonitromethanes\ CHal2NO1

Photodimerization of tri~uoronitrosomethane\ followed by acid hydrolysis and oxidation withsilver oxide\ lead to bis"tri~uoromethyl#aminoxyl radical ð46JCS0630Ł which reacts with alkyl halideswith formation of O!alkyl!N\N!bis"tri~uoromethyl#hydroxylamines[ The O!methyl compound wasprepared in this way by reaction with iodomethane at RT "Scheme 06# ð58JCS"A#320Ł[ The bis"tri!~uoromethyl#aminoxyl radical also reacts with activated positions of alkanes with formation of N\N!

130Three Halo`ens

bis"tri~uoromethyl#hydroxylamine and O!alkyl!N\N!bis"tri~uoromethyl#hydroxylamines "Scheme07# ð62JCS"P0#0981\ 64JCS"D#1114\ 64JCS"P0#1922\ 79JFC"05#280\ 70JCS"P0#344\ 70JFC"06#220Ł[

F3CNO N O

F3C

F3C

NO N OH

F3C

F3C

N O•

F3C

F3C

N OMe

F3C

F3CHCl/H2O Ag2O MeI

96%

hν

Scheme 17

Scheme 18

N OH

F3C

F3C

N O•

F3C

F3C

N OR

F3C

F3CAg2O RH

N OH

F3C

F3C+

R = CMe2, CH2TMS, CH(Ph)CN, CH2SMe, CH2Ar

9–98%

N!"Tri~uoromethyl#hydroxylamine "as its diethyl ether adduct# is formed in 37) yield whentri~uoronitrosomethane is treated with potassium hydrogen sul_te in H1O:Et1O\ followed byhydrolysis "Scheme 08# ð71JCS"P0#574Ł[ Tri~uoronitrosomethane reacts as an ene reaction compon!ent\ for instance with propene with formation of N!"tri~uoromethyl#!N!allylhydroxylamine in 89)yield "Equation "59## ð79JCS"P0#0859Ł[ O!Aryl!N\N!bis"tri~uoromethyl#hydroxylamines are preparedin high yield "×79)# from the sodium salt of N\N!bis"tri~uoromethyl#hydroxylamine and an arylchloride ð70JFC"06#74\ 70JFC"06#480Ł[ O!Benzylated derivatives have been prepared in high yield"×79)# from benzyl chlorides and mercury"II# bisðbis"tri~uoromethyl#aminoxideŁ ð62JCS"P0#0981Ł[

Scheme 19

N SO3– K+

F3C

HOKHSO3

H2O/Et2O–196–20 °C, 2h

NH•OEt2F3C

HOF3CN O

H3O+

48%

F3CN O + F3C N

OH

(60)

Tri~uoronitrosomethane may be prepared by di}erent methods\ for example by free radicalsubstitution of iodotri~uoromethane with NO:Hg:hn "78) yield# ð43JCS801Ł or by the heating ofCF2C"1O#ONO "089>C\ 45) yield# ð51JOC0953Ł or CF2C"1O#NHOH "52) yield# ð59DOK"021#591Ł[Trichloronitrosomethane has been prepared similarly by the heating of CCl2C"1O#NHOH"89Ð84>C\ 51) yield# ð42JCS1964Ł and by treatment of CCl2SO1Na with HNO2 "45) yield#ð59DOK"021#591Ł[

Nitrotri~uoromethane is available in 38) yield by oxidation of the corresponding nitroso com!pound with Mn1O6 ð42JCS1964Ł[ Trichloronitromethane "chloropicrin# which is commercially avail!able and useful as an insecticide and as a synthetic building block\ can be prepared in a number ofways including the chlorination of nitromethane with strongly alkaline aqueous sodium hypochlorite"89) yield# ð33USP1254870Ł[

"vi# N!"Trihalomethyl#sulfenamides\ CHal2NR0SR1

N\N!Bis"tri~uoromethyl#alkanesulfenamides may be prepared by the reaction of mercury"II#bis"tri~uoromethyl#amide with an alkanesulfenyl chloride[ N\N!Bis"tri~uoromethyl#methane!sulfenamide has been prepared in 85) yield by this method ð55JINC0712Ł[ Another method is theaddition of N\N!bis"tri~uoromethyl#!S!"chloro#thiohydroxylamine\ formed by the reaction of N!chloro!N\N!bis"tri~uoromethyl#amine with elemental sulfur ð53USP2010001Ł\ to alkenes which leadsto N\N!bis"tri~uoromethyl#!1!chloroalkanesulfenamides "Scheme 19# ð70JFC"08#80Ł[


F3CN

F

F

N Cl

F3C

F3C

N SCl

F3C

F3CN S

F3C

F3C

CClMe2

i, KFii, Cl2

S225 °C

Scheme 2070% 81%

"vii# Metal "trihalomethyl#amides\ CHal2NRM

"Trihalomethyl#amines are poor nucleophiles\ but may be converted into stronger nucleophilesby conversion to metal "trihalomethyl#amides[ The starting material for metal "tri~uoromethyl#!amides is tri~uoromethyl isocyanide di~uoride "CF2N1CF1# which by reaction with HgF1 or KFforms the corresponding metal amides ð47JA2593\ 64IZV1168Ł[

"viii# Miscellaneous compounds

Tri~uoronitrosomethane reacts with amines with formation of N!tri~uoromethyldiazenes"CF2N1NR# ð50DOK"030#246\ 57ZOB698Ł[ N\N!Bis"dibromomethylene#hydrazine "Br1C1NN1CBr1#reacts with silver"II# ~uoride with formation of N\N!bis"tri~uoromethyl#diazene "CF2N1NCF2# in81) yield\ which may be further transformed into the corresponding hydrazine "CF2NHNHCF2#by treatment with H1S\ HI or PH2 ð51DOK"031#243\ 51JA1226\ 55JOC2722Ł[

5[96[1[1[1 Three halogens and a phosphorus function

Dialkyl! and diarylphosphines react with tetrachloromethane in the presence of triethylamine toyield the corresponding phosphines "CCl2#PR1 in 76Ð84) yield ð80PS"44#074Ł and dichloro!methylenephosphines CCl11PR react with CCl3 in ether in the presence of "Et1N#2P to formbis"trichloromethyl#phosphines "CCl2#1PR in 67Ð70) yield ð81ZOB837Ł[ Tri~uoromethylphos!phaalkenes "CF2#P1CFOR have been prepared from the corresponding di~uoromethylenecompounds ð82ZN"B#47Ł[ The iminomethylenephosphine "CF2#P1C1NBut has been prepared from"CF2#P1CF1 and t!butylamine and the cyclic diphosphane "3# is available from "CF2#P1CF1 and1\2!dimethyl!1\3!butadiene ð80ZN"B#867Ł[ Per~uoro!1!phosphapropene upon addition of an alcoholand subsequent treatment with a secondary amine yields the derivative "CF2#P1C"OR#NR1

"R�Me\ Et# in 47) yield ð80HAC274Ł[

(4)

P

PCF3

CF3

Tri~uoromethanephosphonic acid can be obtained by hydrolysis of diiodo"tri~uoromethyl#!phosphine ð43JCS2487Ł[ With alcohols diiodo"tri~uoromethyl#phosphine forms tri~uoromethane!phosphonic acid monoalkyl esters in 17Ð48) yield ð77ZOB0414Ł[ Trimethyl phosphite reactsupon re~ux with tetrachloromethane to form dimethyl trichloromethanephosphonate in 80) yieldð35ZOB0410Ł[ This ester\ when re~uxed with concentrated hydrochloric acid\ is quantitativelyconverted to trichloromethanephosphonic acid dihydrate ð44JA1758Ł[

Azidobis"tri~uoromethyl#phosphine reacts with "CF2#1P0N1PPh2 to form "CF2#1P0N1P!"CF2#10N1PPh2 ð82JOM"337#108Ł[ Aminobis"trichloromethyl#phosphines such as Me1NP"CCl2#1can be oxidized with hydrogen peroxide to the corresponding phosphine oxides and with S7 tothe corresponding phosphine sul_des[ With chlorine the corresponding chlorophosphoniumchlorides are formed which are dealkylated upon heating to MeN1P"CCl2#1[ Aminobis"tri!chloromethyl#phosphines can be cleaved with HCl to form ClP"CCl2#1 ð82ZOB0139Ł[ Dibromo"tri!~uoromethyl#phosphine "CF2#PBr1 can be converted to the corresponding "tri~uoromethyl#!phosphinylbistriazolide which is useful for the tri~uoromethylphosphonation of carbohydratesð82TL038Ł[

132Three Halo`ens

5[96[1[1[2 Three halogens and an As\ Sb\ or Bi function

Mixed di~uorohalomethylarsines are accessible by treatment of arsenic"III# chloride\ bromide oriodide\ respectively\ with di~uorocarbene\ generated from "CF2#1Cd = 1MeCN[ Arsenic"III# ~uoridereacts with the same cadmium reagent with tri~uoromethylation ð89ZAAC"477#15Ł[ Tris"tri~uoro!methyl#stilbine ð89JFC"35#154Ł and tris"tri~uoromethyl#bismuthine ð76JOM"223#212Ł are accessiblefrom the appropriate element halides and "CF2#1Cd[ Diphenyl"tri~uoromethyl#bismuthine andphenylbis"tri~uoromethyl#bismuthine have been prepared from the corresponding phenyl!halobismuthines and "CF2#1Cd ð80JOM"306#C36Ł[ Bis"tri~uoromethyl#chloroarsine yields the cor!responding azide when treated with sodium azide ð81JST"157#278Ł and azidobis"tri~uoromethyl#arsinereacts with triphenylphosphine to give "CF2#1As0N1PPh2 ð82JCS"D#552Ł[

5[96[1[2 Three Halogens and a Metalloid

5[96[1[2[0 Three halogens and a silicon function

Compounds with an "a! or b!~uoroalkyl#silane structure are prone to rearrangement with elim!ination of a ~uorosilane R2SiF ð48QR122\ 53AOC"0#032Ł[

The construction of the CF2SiR2 moiety requires several steps such as insertion of di~uorosilyleneinto the C0I bond of tri~uoroiodomethane\ metathesis of CF2SiFI with SbF2 to yield CF2SiF1\ andsubsequent reduction with LAH to tri~uoromethylsilane ð75JOM"205#30Ł^ also bis"tri~uoromethyl#!silane has been prepared ð89JOM"274#196Ł[ A more convenient procedure starts from bromo!tri~uoromethane\ tris"diethylamino#phosphine\ and an appropriate silicon halideð82OM3829Ł[ Tetra!kis"trichloromethyl#silane has been prepared in 53) yield by photochlorination of "CH1Cl#Me2Si[The corresponding chlorination of TMS leads to destruction of the reaction mixtureð78ZOB1517Ł[

A reagent prepared from tetrakis"dimethylamino#ethylene and CBr2F reacts with organo!chlorosilanes RnSiCl3−n to give dibromo~uoromethylsilanes "CBr1F#SiRnCl2−n in 16Ð43) yieldð82OM3829Ł[

5[96[1[2[1 Three halogens and a boron function

Many tri~uoromethyl boranes are unstable due to the vacant orbital on boron\ which causes halidemigration from carbon to boron with formation of di~uorocarbene[ Oxygen or nitrogen"III# ligandsas well as tetracoordination of the boron atom increase stability[

Dibutyl"tri~uoromethyl#borane\ "CF2#BBu1\ is formed in the reaction between potassium di!butylborate"I# and tri~uoroiodomethane[ The former reacts with boron tri~uoride to yield di~uo!ro"tri~uoromethyl#borane\ CF2BF1\ ð56JA2335Ł[Tris"tri~uoromethyl#borane\ "CF2#2B\ is an extremelystrong Lewis acid and can only be isolated in the shape of adducts with Lewis bases[ For example\"CF2#2B =NR0R1R2 can be obtained from "dialkylamino#dichloroboranes "R0R1N#BCl1and bromotri~uoromethane:tris"diethylamino#phosphine or tri~uoroiodomethane:tetrakis"di!methylamino#ethylene and subsequent alkylation of the secondary amine adducts so formedð82JOM"335#14Ł[

In dichloromethane solution aminohaloboranes such as Et1NBCl1 and Et1NBBr1 react withCF2Br:P"NEt1#2 to yield the corresponding "CF2#BClNR1\ "CF2#BBrNR1\ and "CF2#1BNR1

ð78JOM"267#014Ł[Dimethylaminobis"tri~uoromethyl#borane "CF2#1BNMe1 "4# inserts into oxiranes to form the

corresponding oxaazoniaboratacyclopentanes "5# ð82ZN"B#824Ł[ Compound "4# also undergoes enereactions with alkenes ð82JOM"345#08Ł[ With diazoalkanes "4# forms the corresponding three!membered rings "6# ð82AG318Ł[

B

N

F3C CF3

Me Me

(5)

Me2NB

O

R

F3C CF3

R = Me, CH2F, CF3, Et, Bn

(6)

+

–NMe2

B

R1

R2

F3C CF3

R1, R2 = H, Bn, TMS

+

(7)

–


Hexamethyldistannane reacts metathetically with tri~uoroiodomethane to form "tri~uoro!methyl#trimethylstannane[ The latter reacts further with boron tri~uoride to generate ðMe2SnŁ¦

ð"CF2#BF2Ł− which in turn can be converted to the corresponding potassium salt ð59JA4187Ł[

5[96[1[2[2 Three halogens and a germanium function

Germanium"II# iodide has been treated with tri~uoroiodomethane in an autoclave at 029Ð024>Cand found to give triiodo"tri~uoromethyl#germane\ "CF2#GeI2\ and diiodobis"tri~uoromethyl#germane\ "CF2#1GeI1[ The iodine atoms of the former can be exchanged for chlorine by treatmentwith silver"I# chloride with formation of "CF2#GeCl2 ð51JA787Ł[ The compounds "CF2#GeF2

and K1ð"CF2#GeF4Ł have been similarly prepared ð59JA5117Ł[Atomic germanium in a solvent slurry reacts with tetrachloromethane to form "CCl2#GeCl2 and

with bromotrichloromethane to form "CCl2#GeBr2 in low yield ð77BCJ2991Ł[

5[96[1[3 Three Halogens and a Metal Function

The chemistry of "tri~uoroalkyl#metal compounds has previously been presented in a textbook byEmele�us ðB!58MI 596!91Ł and in reviews by Trichel and Stone ð53AOC"0#032Ł[ The synthetic methodsfor the preparation of "per~uoroorgano#metallic compounds have been reviewed by ChambersðB!62MI 596!90Ł\ and tri~uoromethyl!containing transition metal complexes by Morrisonð82AOC"24#100Ł[

Of the di}erent "tri~uoromethyl#metal complexes prepared to date\ donor ð0\1!dimethoxy!ethanel"glyme# or DMFŁ stabilized bis"tri~uoromethyl#cadmium seems to be the most reliable ande.cient tri~uoromethylating agent[ Other "tri~uoromethyl#metal complexes have been prepared\ forwhich some application in the electronic industry may be found\ such as the stable gold complexes[

"i# Trihalomethyl alkali and earth alkali metals\ CHal2M "M�Li\ Na\ K\ Cs\ M`#

The preparation of a!haloalkyl Grignard reagents has been reviewed byVillie�ras ð60MI 596!90Ł[ Thetrihalomethyl alkali and earth alkali metals are very di.cult to isolate due to the dihalocarbenecharacter of the carbon[ They are therefore most often prepared in situ and used without isolation[ Inthe case of "trichloromethyl#lithium the position of the equilibrium at −099>C "Equation "50## lies tothe side of "trichloromethyl#lithium ð64JA076Ł[

Cl3CLi :CCl2 + LiCl (61)

Ligand exchange has been attempted in the synthesis of "tri~uoromethyl#lithium and !magnesium[When tri~uoroiodomethane is treated with methyllithium in diethyl ether\ "tri~uoromethyl#lithium isformed initially\ but this complex decomposes into lithium ~uoride and di~uorocarbene whichdimerizes[ This is also the case with magnesium ð43JA363\ 53AOC"0#032Ł[

According to Ko�brich\ lithiation of 1\1!diphenyl!0!bromoethene with "dichloromethyl#lithiumand subsequent treatment with tetrachloromethane gives "trichloromethyl#lithium and 1\1!diphenyl!0\0!dichloroethene[ "Trichloromethyl#lithium has also been prepared in situ from butyllithium andtetrachloromethane or trichloromethane and then treated with a number of electrophiles by Hoeget al[ ð54JA3036Ł[ "Trichloromethyl#lithium\ !sodium\ !potassium and !caesium have\ furthermore\been prepared and investigated by IR in an Ar:CCl3 matrix at 04 K ð64JA076Ł[

"Tribromomethyl#lithium should be available by the reaction of butyllithium with tetra!bromomethane[ No data have\ however\ been presented ð56AG04Ł[

"Trichloromethyl#magnesium chloride has been prepared from isopropylmagnesium chloride andCCl3 at −004>C in THF or with CHCl2 at −67>C in THF:hexamethylphosphoric triamide "HMPT#"79:19# in 59) and 69) yield\ respectively[ "Tribromomethyl#magnesium chloride was preparedsimilarly with CBr3 at −004>C in THF or with CHBr2 at −84>C in THF:HMPT "79:19# in 49)yield ð56BSF0419Ł[

134Three Halo`ens

"ii# Trihalomethylaluminum\ !`allium\ !indium and !thallium\ CHal2MRn\ "M�Al\ Ga\ In\ Tl#compounds

Tris"tri~uoromethyl#gallane has been prepared in 25) yield by Guerra et al[ by treating galliumtribromide with a slight excess of Cd"CF2#1 = glyme in CH1Cl1[ Further treatment with tri!methylphosphine or trimethylarsine leads to ð"CF2#2GaPMe2Ł and ð"CF2#2GaAsMe2Ł in quan!titative yields ð89JOM"289#C62Ł[ Naumann et al[ were able to prepare the following tri~uoromethylgroup 02 metal complexes ðGa"CF2#1Cl =DMFŁ "in 28) yield#\ ðGa"CF2#2 =DMFŁ "31)#\ðCd"NCMe#1ŁðGa"CF2#3Ł "38)#\ ðIn"CF2#1Cl =DMFŁ "21)#\ ðIn"CF2#2 = 1NCMeŁ "25)# andðTl"CF2#2 = 1DMFŁ "34)# from ðCd"CF2#1 =D\ D�glyme\ diglyme\ MeCNŁ and GaCl2\ InCl2 orTlCl2[ The reactions were conducted in CH1Cl1\ MeCN or DMF at −29 to 39>C ð80JOM"396#0Ł[

"iii# Trihalomethyltin and !lead\ CHal2MRn "M�Sn"II#\ Sn"IV#\ Pb"IV## compounds

Tri~uoromethyl"trimethyl#stannane has been prepared in 70) yield by heating at 79>C for 19 hor irradiation of a mixture of tri~uoroiodomethane and hexamethyldistannane "Me2SnSnMe2#[Chlorination of "tri~uoromethyl#trimethylstannane leads to "tri~uoromethyl#dimethyltin chloride"Scheme 10# ð47JOC0454\ 59JA0777Ł[

SnCl4 + MeMgI

dibutyl etherreflux

SnMe4

89%

SnBr4

120 °C, 3 hMe3SnBr

89%

Na/NH3 (l)Me3SnSnMe3

71%

Me3SnSnMe3

CF3I80 °C, 20 h

closed vessel–Me3SnI

Me3SnCF3

Cl2Me2(CF3)SnCl + MeCl

Scheme 21

The "tri~uoromethyl#tin halides have been prepared[ Thus\ when tin tetrabromide is heated for1×04 h at 009>C in an ampoule with Hg"CF2#1\ "CF2#2SnBr "7)#\ "CF2#1SnBr1 "05)#\ and CF2SnBr2

"44)# are formed\ whereas when "CF2#1Cd =diglyme is used as tri~uoromethylating reagent"CF2#3Sn "34)# and CF2SnBr2 "09Ð14)# are collected ð81JOM"322#52Ł[ Tris"tri~uoromethyl#tin iod!ide may be prepared from tetrakis"tri~uoromethyl#stannane^ either by treatment with HI or BrI2

"giving 49Ð79) yield of "CF2#2SnI and 19Ð49) yield of "CF2#1SnI1#[ "Tri~uoromethyl#tin triiodideis formed similarly by HI treatment of tri~uoromethyltin tribromide in 83) yield[ When theseproducts are treated with AgCl for 2 h at 49>C\ the corresponding chlorides are formed in 84)yield[ Tris"tri~uoromethyl#tin ~uoride is formed upon heating "2 h at 099>C# of tetrakis!"tri~uoromethyl#stannane ð81JOM"322#52Ł[

Mixed "tri~uoromethyl#methylstannanes ð"CF2#nSnMe3−nŁ have been prepared by ligand exchangebetween tetramethylstannane and tetrakis"tri~uoromethyl#stannane ð81JOM"322#52Ł[

Mono!\ bis! and tris"tri~uoromethyl#stannane may be prepared by reduction of "CF2#nSnX3−n

with tributylstannane at −49>C for 1 h[ The yields were 78)\ 81) and 34)\ respectivelyð81JOM"323#048Ł[

A number of "tri~uoromethyl#lead complexes have been prepared in a stepwise manner by Eujenand Patorra ð81JOM"327#46Ł[ Bis"tri~uoromethyl#cadmium reacts with trimethyl! and triethylleadbromide in sulfolane at 69>C to give "CF2#PbMe2 "40) yield# and "CF2#PbEt2 "45)#[ Bromination"Br1# at 9>C or iodination "I1# at RT gave the corresponding "tri~uoromethyl#dialkyllead halides"alkyl�methyl or ethyl# in quantitative yields[ The "tri~uoromethyl#dialkyllead bromides may betransformed into the bis"tri~uoromethyl#dialkyllead complexes ""CF2#1PbMe1 "36) yield# and"CF2#1PbEt1 "49)## by treatment with Cd"CF2#1[ Bis"tri~uoromethyl#methyllead bromide wasthen prepared in 64) yield\ by bromination at −14>C "61 h# of bis"tri~uoromethyl#dimethyllead\which by further reaction with Cd"CF2#1 gave tris"tri~uoromethyl#methyllead in 18) yield[Tetrakis"tri~uoromethyl#lead has not been prepared and must be expected to be rather unstablelike the analogous tetrahalolead complexes ð81JOM"327#46Ł[

"iv# Trihalomethylzinc\ !cadmium and !mercury\ CHal2MR "M�Zn\ Cd\ H`"II## compounds

Miller et al[ failed to prepare trihalomethylzinc iodides or bromides from zinc and tri!haloiodomethanes or trihalobromomethanes in glyme ð46JA3048Ł whereas Burton and Wiemers


did so by treating activated "acid washed# zinc or cadmium with dibromodi~uoromethane orbromochlorodi~uoromethane in DMF for 1 h at RT[ When dichlorodi~uoromethane was used\ thereaction had to be carried out at 79>C in a sealed ampoule[ A yield of 79Ð84) of "tri!~uoromethyl#cadmium halide and a yield of 79Ð74) of "tri~uoromethyl#zinc halide was achieved[The "tri~uoromethyl#metal halides were not isolated but stored for later use as 0 M solutions inDMF ð74JA4903Ł[

Bis"tri~uoromethyl#cadmium "00) yield\ 88) purity# and bis"tri~uoromethyl#zinc "7) yield#were prepared at low temperature "³34>C# by the reaction of the metal with hexa~uoroethane in aradio frequency discharge[ The {{naked||\ that is nondonor stabilized\ compounds Cd"CF2#1 andZn"CF2#1 decompose at 9>C and −39>C\ respectively\ but may be stabilized with glymeðCd"CF2#1 = glymeŁ and pyridine ðZn"CF2#1 = 1pyridineŁ ð75JA3092\ 80CJC216Ł[ The bis"tri~uoro!methyl#cadmium glyme adduct may also be prepared from dimethylcadmium and bis"tri~uoro!methyl#mercury in glyme ð79CC560\ 70JA1884\ 75JA721Ł[

Alkali metal tetrakis"tri~uoromethyl#cadmates have been prepared and investigated by NMR\but not puri_ed ð78JOM"257#020Ł[

The formation of "tri~uoromethyl#mercury iodide is accomplished photochemically in 79) yieldby treatment of tri~uoroiodomethane with mercury at 049>C ð37JCS1077Ł[ Further treatment of thisisolatable intermediate with cadmium amalgam at 019Ð029>C causes the formation of bis"tri!~uoromethyl#mercury in 79Ð89) yield ð38JCS1842Ł[ Bis"tri~uoromethyl#mercury is also formedfrom mercury"II# oxide and tris"tri~uoromethyl#phosphine upon 11 h heating at 099>C in a sealedtube "73) yield# ð59JA4648Ł[ "Trichloromethyl#mercury"II# chloride and bis"trichloro!methyl#mercury have been prepared\ by halide substitution\ from mercury"II# chloride or mercuricbromide with sodium trichloroacetate[ The intermediate mercury"II# trichloroacetate decomposesinto the trichloromethyl derivative with elimination of carbon dioxide[ The reaction is conductedin diglyme at re~ux temperature for 0 h with yields of 58Ð66)[ The actual ratio of sodiumtrichloroacetate to mercury"II# chloride determines whether the product is bis"trichloro!methyl#mercury or the "trichloromethyl# mercury"II# halide ð52JOC0018Ł[

"v# Trihalomethylcopper\ !silver and !`old\ CHal2MRn "M�Cu"I#\ A`"I#\ Au"I#\ Au"III##compounds

The tri~uoromethyl complexes of group 00 may be arranged into the following order of stabilityaccording to Nair and Morrison] AuCF2×AgCF2×CuCF2 ð78JOM"265#038Ł[

"Tri~uoromethyl#copper"I# is probably formed initially in some coupling reactions\ for example\when tri~uoroiodomethane is heated "029Ð039>C# with metallic copper in DMF[ This intermediateis trapped by aryl iodides with formation of the corresponding tri~uoromethylarenes ð58TL3984\69CPB1223Ł[ This method has later been improved by Kobayashi et al[ to include the correspondingreaction with aliphatic halides[ They shook tri~uoroiodomethane and copper powder in HMPA at019>C for 1[4 h[ After removal of excess copper powder the aliphatic halide was added and themixture stirred at RT or 69>C under N1 atmosphere[ They were able to tri~uoromethylate aliphaticand vinylic halides in 02Ð70) yield by the "tri~uoromethyl#copper"II# iodide formed in situð68TL3960Ł[

The "tri~uoromethyl#silver"I# trimethylphosphine complex has been prepared from silver acetateand Cd"CF2#1 = glyme in Et1O^ after 09 min trimethylphosphine was condensed into the reactionvessel[ The "tri~uoromethyl#silver"I# trimethylphosphine complex\ ð"CF2#AgPMe2Ł was isolated in25) yield ð78JOM"265#038Ł[

"Tri~uoromethyl#gold"I# complexes stabilized "air and moisture insensitive# by trimethyl!\ triethyl!or triphenylphosphine ""CF2#AuL\ L�PMe2\ PEt2 or PPh2# have been prepared in 54Ð64) yieldfrom ClAuL "L�PMe2\ PEt2 or PPh2# and Cd"CF2#1 = glyme in CH1Cl1[ Bis"tri~uoromethyl#mercurywas ine}ective as a tri~uoromethylating agent\ even at 049>C ð78JOM"265#038\ 78OM0387Ł[ Thesegold"I# complexes are oxidized by elemental bromine or iodine with formation of phosphine stabil!ized "tri~uoromethyl#gold"III# dihalides in ½24) yield ""CF2#AuX1L\ L�PMe2\ PEt2 or PPh2#[The analogous addition of tri~uoroiodomethane to "CF2#AuL "L�PMe2 or PEt2# in CH1Cl1 leadsto bis"tri~uoromethyl#gold"III# iodide in 79) yield "87) cis\ 1) trans# ð78JOM"265#038\ 78OM0387Ł[The unstable tris"tri~uoromethyl#gold"III# complex has been prepared by Guerra et al[\ from goldvapors and plasma!generated tri~uoromethyl radicals at −085>C ð75JOM"296#C47Ł\ and may alsobe obtained as the trimethylphosphine stabilized analog ð"CF2#2Au"PMe2#Ł by reaction of "CF2#1!AuI"PMe2# with Cd"CF2#1 = glyme in the presence of excess tri~uoroiodomethane in 79) yield

136Three Halo`ens

ð78OM0387Ł[ The organogold"I# complex ð"CF2#Au"−C2N¦0Me#Ł was prepared similarly by

Dryden et al[ in 67) yield ð81CM868Ł[ Nair and Morrison made ð"CF2#2Au"PEt2#Ł in 19Ð49) yieldfrom CF2I and ð"CF2#Au"PEt2#Ł ð78JOM"265#038Ł[

Bis"tri~uoromethyl#gold"III# m!halide dimers ðAu"CF2#1"m!X#Ł1 have also been prepared\ by avapor deposition technique\ from gold treated with excess "0 ] 099# of either bromotri~uoromethaneor tri~uoroiodomethane[ The products may be recrystallized from pentane and are moderately airand light sensitive[ The m!bromide was isolated in 05) yield wheras the m!iodide was isolated in7) yield ð89IC2141Ł[

"vi# Miscellaneous trihalomethyl transition metal\ CHal2MRn "M�transition metal# compounds

A number of platinum complexes containing tri~uoromethyl as a ligand have been prepared byligand exchange from Pt"CF2#nMe1−nNBD "NBD\ norbornadiene# ð82JOM"342#296Ł[ This complexis itself made from PtMe1NBD by tri~uoromethyl:methyl exchange with CF2I ð77JOM"231#288\82JOM"342#188Ł[ Tri~uoromethyl:methyl exchange has also been used to prepare other platinumcomplexes containing tri~uoromethyl as a ligand ð89IC1385Ł[

Tri~uoroiodomethane adds to cis!PtMe1L1 "L�PMe1Ph# at 079>C under vacuum to givePtMe1L1"CF2#I with CF2 and I in axial positions ð69IC1445Ł[ Hydrido tri~uoromethyl complexes ofplatinum"II# have been prepared by Michelin et al[ ð89OM0338\ 78JCS"D#0038Ł[

Other transition metal complexes with tri~uoromethyl as ligand have been prepared[ Theseinclude rhodium ð89JOM"277#280\ 80CC054Ł\ ruthenium ð89JOM"284#216\ 89JOM"286#198Ł\ osmiumð89JOM"284#216Ł\ iridium ð89JOM"283#504Ł\ manganese ð50JA0487Ł and cobalt complexes ð50JA2482Ł[


6.08Functions Containing TwoHalogens and Two OtherHeteroatom SubstituentsANASTASSIOS VARVOGLISUniversity of Thessaloniki, Greece


5[97[1 TWO HALOGENS AND TWO CHALCOGEN FUNCTIONS 149

5[97[1[0 Two Haloèns and Two Oxyèn Functions 1495[97[1[0[0 Di~uoro compounds 1495[97[1[0[1 Dichloro and dibromo compounds 140

5[97[1[1 Two Haloèns and Two Sulfur Functions 1415[97[1[1[0 Di~uoro compounds 1415[97[1[1[1 Dichloro\ dibromo\ and diiodo compounds 143

5[97[1[2 Two Haloèns\ an Oxyèn\ and a Sulfur Function 1445[97[1[3 Two Haloèns and Other Chalcoèn Functions 145

5[97[2 TWO HALOGENS AND ONE CHALCOGEN FUNCTION 145

5[97[2[0 Two Haloèns\ a Chalcoèn\ and a Nitroèn Function 1455[97[2[0[0 Oxyèn compounds 1455[97[2[0[1 Sulfur compounds 146

5[97[2[1 Two Haloèns\ a Chalcoèn\ and Other Functions 147

5[97[3 TWO HALOGENS AND TWO GROUP 04 ELEMENT FUNCTIONS 147

5[97[3[0 Two Haloèns and Two Nitroèn Functions 1475[97[3[0[0 Diamines and their derivatives 1475[97[3[0[1 Dinitro compounds 1595[97[3[0[2 Cyclic compounds 150

5[97[3[1 Two Haloèns and Two Phosphorus Functions 1525[97[3[1[0 Bis"phosphonates# 1525[97[3[1[1 Cyclic compounds 1535[97[3[1[2 Miscellaneous compounds 154

5[97[3[2 Two Haloèns and Two Other Group 04 Element Functions 155

5[97[4 TWO HALOGENS AND ONE GROUP 04 ELEMENT FUNCTION 155

5[97[4[0 Two Haloèns\ a Phosphorus\ and a Metalloid or Metal Function 155

5[97[5 TWO HALOGENS AND TWO METALLOID FUNCTIONS 156

5[97[5[0 Two Haloèns and Two Silicon Functions 1565[97[5[0[0 Linear carbosilanes 1565[97[5[0[1 Cyclic carbosilanes 157

5[97[5[1 Two Haloèns and Two Boron or Other Metalloid Functions 158

5[97[6 TWO HALOGENS AND ONE METALLOID FUNCTION 158

5[97[6[0 Two Haloèns\ a Silicon\ and a Metal Function 158

5[97[7 TWO HALOGENS AND TWO METAL FUNCTIONS 169

138

149 Two Haloèns and Two Other Heteroatoms

5[97[0 INTRODUCTION

A great variety of functionalities characterize the family of compounds containing functions withtwo halogens and two other heteroatom substituents^ however\ the family has few representatives[Heteroatom substituents include O\ S\ Se\ Te\ B\ N\ P\ As\ Si\ Ge\ and some metals\ and the halogenatoms are F and Cl in most cases[ Several members of the family stand on the verge of organic andinorganic chemistry\ particularly when relatively small molecules are involved without hydrogenatoms[ It is emphasized that the experimental work with elemental ~uorine requires special con!ditions and considerable expertise[

5[97[1 TWO HALOGENS AND TWO CHALCOGEN FUNCTIONS

5[97[1[0 Two Halogens and Two Oxygen Functions

5[97[1[0[0 Di~uoro compounds

Addition of ~uorine to the carbonyl bond of simple per~uorooxo compounds leads to theformation of either stable adducts "èm!~uorohypo~uorites# or to products of further trans!formation[ In the case of FC"O#OF "0#\ both types of product may be formed[ Thus\ the simplestcompound of this class\ di~uorodioxirane "3#\ has been obtained from "0# and either ~uorine orchlorine ~uoride in a ~ow system using a pelletized caesium ~uoride catalyst[ After the initial attackof ~uoride on carbon\ an electron transfer follows between "1# and the halogen^ the free radicalintermediate "2# cyclizes to "3#\ or may produce "4# when ClF is used "Scheme 0# ð82AG"E#894Ł[Bis"~uoroxy#di~uoromethane was the unique product obtained from the reaction between FC"O#OFand ~uorine\ again in the presence of caesium ~uoride\ in a Monel bomb "Equation "0## ð56JA4050Ł[The same product was also formed from the double addition of ~uorine to CO1\ catalyzed bycaesium ~uoride ð56JA0798\ 56JA0851Ł[ A variation involves the action of ~uorine upon sodiumtri~uoroacetate or sodium oxalate ð56JA0700Ł[ Another hypo~uorite\ the peroxide "6#\ was producedby the addition of ~uorine to the carbonyl bonds of "5# "Equation "1## ð56CC769Ł[ In some esters ofthionocarbonic acid the C1S group was directly transformed into CF1 upon treatment with ~uorineîn this way\ compounds of the type "RCH1O#1CF1 were formed "where R is a polynitromethylgroup# ð78IZV002\ 82IZV1402Ł[ Similar compounds were obtained by substitution from the cor!responding CCl1 analogues and SbF4 in SO1Cl1[

F

O

OF

O–

OF

F

F

O•

OF

F

F O

OF

F

OCl

OF

F

F

CsF, RT F2 or ClF+

Scheme 1

(1) (2) (3) (4) 20–50% (5) 0–70%

F

O

OF

OF

OF

F

F

CsF, RT+ F2 (1)

F OO F

O

O

F OO F

FO

OF

+ 2F2

F

F

KF, –95 °C(2)

(6) (7)

Bis"~uoroxy#di~uoromethane reacts with halogenated alkenes\ probably through the free radical"2# which transfers its OCF1O group to the double bond[ The products are either halogenatedacetals of methanal\ for example "7#\ or 0\2!dioxolanes\ for example "8# "Scheme 1#[ Upon treatmentof the latter with Zn and K1CO2 in DMF\ chlorine was eliminated and per~uoro!0\2!dioxole wasproduced ð57IC513\ 81EUP388046\ 81EUP388047\ 81JFC"47#032\ 81JFC"47#189Ł[ Photochemically\ F1C"OF#1also adds its OCF1O group to the double bond of per~uoro Dewar benzene^ the reaction is complexand the major product "5) yield# "09# rearranges thermally to "00# "Scheme 2#[ ð68JOC1702Ł[ Cyclic

140Two Chalco`ens

thionocarbonates have been converted into 1\1!di~uoro!0\2!dioxolanes by ~uorinolysis of the C1Sfunction using Bu3NH1F2 and N!iodosuccinimide ð83SL140Ł[

(8) 90%

F3CF2CO OCF2CF3

F F OF

OFF

F

F

F F

F F

Cl Cl

F, –180 °CO O

FClCl

F

F F(9)

Scheme 2

(11)(10)

OF

OFF

F

hν ∆

F

F

F

F

F

F+ O

OF

FF

FF

FF

F

OO

O

O

FF

FF

F

FF

F

Scheme 3

Some di~uorodialkoxymethanes are produced in a di}erent way\ after halogenolysis of the doublebond of either F2CN1C"OR#1 or F4SN1C"OR#1 by chlorine ~uoride "Equation "2## ð89JFC"37#284Ł[In some cases ~uorine can substitute for hydrogen attached to an sp2 carbon[ Per~uorodi!methoxymethane and per~uoro!0\2!dioxane*as well as other products*have been reported toresult from electrochemical ~uorination of methyl 2!methoxypropionate ð65ZOR656Ł[ The physicalproperties of such compounds have been described but their preparation has not yet been docu!mented ð81MI 597!90\ 82MI 597!90Ł[ Chemical and electrochemical methods have been used to ~uorinatethe methanal derivative "01# to "02# "Equation "3## ð80JFC"44#202Ł[

N

OCH2CF3

OCH2CF3F3C OCH2CF3

OCH2CF3F

F+ 2ClF + F3CNCl2 (3)

(4)

OCF2CF2SO2F

OCF2CF2SO2F

OCF2CF2SO2F

OCF2CF2SO2FF

F

F2, NaF

(12) (13)

The action of ~uorine on polymethylene oxide gives mainly a per~uoropolymer\ but it also bringsabout ~uorinolysis\ with partial ~uorination and depolymerization^ among the products identi_edwere F2COCF1OCF1H and HF1COCF1OCF1H ð70JCS"P0#0210Ł[ Chlorine in F1CCl1 is substitutedby two ~uorosulfato groups in its reaction with ClOSO1F^ F1CBr1 reacts similarly with the peroxycompound FO1SOOSO1F[ In both cases the product is F1C"OSO1F#1 ð54IC0717\ 63IZV224Ł[ Ozonationof tetra~uoroethylene gave rise to an apparently stable moleozonide ð57CI"M#086Ł[ Singlet oxygenreacted with tetra~uoroethylene at −49>C to produce peroxidic per~uoroethers\ which upon strongand prolonged heating were converted into a mixture containing\ inter alia\ per~uoro!0\2!dioxetane\per~uoro!0\2\4!trioxane\ and per~uoro!0\2\4\6!tetraoxocane ð61GEP1000585Ł[ In another patent\ thereaction of the adduct from the reaction between "F1N#1C1NF and KCN with F1C"OF#1 is claimedto give a mixture of products\ including the peroxide F2COOCF1OF ð60USP2474107Ł[ The unusualcompound F2COOCF1OOOCF2\ bearing both peroxide and trioxide functions\ was formed amongother products from a complex reaction between F1C"OF#1 and CsOCF2 ð60IC1068Ł[

5[97[1[0[1 Dichloro and dibromo compounds

The number of compounds in this category is few[ The compounds can be obtained either bycarbonyl "or thiocarbonyl# transformation or by chlorination of a methylene group[ Dichloro!diphenoxymethane "03# was produced upon heating diphenyl carbonate with PCl4^ similarly\phenylene carbonate gave 1\1!dichloro!benzo!0\2!dioxole "04# ð50CB433\ 71JHC0194Ł[ Some diethyl


thionocarbonates of the general formula "RCH1O#1C1S "where R is CF2\ CF1NO1 or CF"NO1#1#were converted into the corresponding CCl1 compounds using either SO1Cl1 or Cl1 ð78IZV002Ł[Photochemical chlorination of 0\2!dioxolane converted it into its perchloro analogue "05#ð61JOC0347Ł[ Some dichlorobis"aryloxy#methanes were similarly prepared via radical!induced chlori!nation of the formaldehyde diaryl acetals with SO1Cl1 or Cl1 ð77S850Ł[ Dibromomethylal\CBr1"OMe#1\ was obtained by simply dropping Br1 into cooled methylal ð11AG378Ł[

OPh

OPhCl

Cl

(14)

O

O

Cl

Cl

(15) (16)

OO

ClCl

ClClCl

Cl

5[97[1[1 Two Halogens and Two Sulfur Functions

5[97[1[1[0 Di~uoro compounds

The reaction of ~uorine with thiocarbonyl compounds usually gives addition products in whichsulfur has also been oxidized[ Carbon disul_de is thus converted into the isolable compound "06#and subsequently into "07# "Scheme 3# ð66IC1863Ł[ The yield of "07# increased when caesium ~uoridewas used as a catalyst^ chlorine ~uoride reacts in a similar way\ leading to the formation of "trans!ClSF3#1CF1 ð72JFC"12#214Ł[ The pseudohalogen CF2SF was also added to carbon disul_de^ nooxidation occurred and the double adduct "CF2SS#1CF1 was obtained in high yield ð81ZN"B#258Ł[The related reaction of F1C1S with CF2SCl gave the adduct "F2CS#CF1SCl ð57CB1506Ł[ The sameproduct was formed upon addition of ClF to F2CSC"S#F\ while a related addition of ClF occurredto the C1S bond of FC"S#SCN ð63CZ098Ł[ Compound "06# reacts with metal ~uorides\ a}ordingrelatively stable anions or cations[ For example\ with CsF a symmetrically bridged anion wasformed\ while with AsF4 in liquid SO1 the stable sulfonium salt F1C"SF2#SF1

¦AsF5− resulted

ð80CB0242\ 81CC0906Ł[ When BF2 in SO1 was used\ "06# a}orded the solvolysis product "08#\ as amixture of two diastereoisomers[ With silylated amines\ "08# was converted into sul_nimides\ forexample "19# or "10# "Scheme 4#[ From the reaction between "08# and HCl\ the rather unstableF1C"S"O#Cl#1 was produced\ which upon hydrolysis gave the bis"sul_nic acid# F1C"SO1H#1[ Direct~uorination at an sp2 carbon has been e}ected in some cases\ for example with "11# which wasconverted into "12#^ this was hydrolyzed to the sulfonic acid "14# through its salt "13# "Scheme 5#ð89IC3477Ł[

(17)

CS2

SF3

SF3F

F SF5

SF5F

F

F2/He, –120 °C F2/He, –80 °C

(18)Scheme 4

S

SF

F

O

O

S

SF

F

O

O

NMe2

NMe2 Me2N-TMS F

F

F

F

(19)

MeN(TMS)2

SNMe

SF

F

(21)

O

O

Scheme 5(20)

(25)Scheme 6

(23)

F2, NaF Ba(OH)2

SO2F

SF5

F

SO2F

SF5F

F SO3H

SF5F

F

(24)

H+(F5SCF2SO3)2Ba

(22)

142Two Chalco`ens

Electrochemical methods have been used for the preparation of "07# and F1C"SO1F#1 ð48JA463\75JFC"21#78Ł[ While the latter was formed from CH1"SO1F#1 in 79) yield\ the former was one ofmany products into which 0\2\4!trithiane was transformed\ for example\ F2CSF3CF1SF4\ and thetrithianic derivative "CF1SF3#2[ A di}erent approach was used for the preparation of the sulfone\PhSO1CF1SPh\ which was obtained from the reaction of PhSO1CHF1 and aqueous NaOH in a two!phase system "CH1Cl1 with Aliquat 225#^ the sulfone was oxidized with H1O1 to F1C"SO1Ph#1ð78JFC"32#42Ł[

A fairly large family of perhalogenated 0\2!dithietanes and their sulfur derivatives is known[Photochemical dimerization of thiophosgene leads in a straightforward way to the formation of"15# ð22CB456Ł[ Upon treatment with SbF4\ this gives rise mainly to compound "16#\ along with somemono! and dichloroper~uoro!0\2!dithietanes "Scheme 6# ð54JOC0264Ł[ A related method started withcompound "17#\ which was converted by strong acids into the isolable salt "18#^ treatment withcaesium ~uoride a}orded the tri~uorodithietane "29# "Scheme 7# ð76CB318Ł[ A similar compound to"18# is the salt "20#\ which can undergo a variety of transformations at its carbocationic center\ asshown in Scheme 8 ð89CB0524Ł[

Scheme 7

(26)

hν SbF5

60%Cl

Cl

S

(27)

2S

S

Cl

Cl Cl

Cl S

S

F

F F

F

(29)

HF/SbF5 or FSO3H/SbF5 F–

X

F

S

(30)

2S

S

F

X

S

S

F

X F

FF+ SbF6

–

(28) X = Cl or SCF3

Scheme 8

S

S

F

FF

S

S X

FF

F

S

S

F

FSCF3

AsF6–

S

S

F

F

S

S

F

FS O

+

(31)

+ AsF6–

Scheme 9

SF

F

X–, SO2, RT

BaCS3 Na2S2O3

X = F, Cl, Br, I

The majority of the reactions of per~uoro!0\2!dithietane involve oxidation at the sulfur[ Depend!ing on the oxidant and the conditions\ several products can be obtained using ~uorine or xenondi~uoride ð73JFC"15#248\ 78JFC"34#114Ł^ chlorine ~uoride ð62JFC"2#06\ 81CB424Ł^ chromium trioxideð79AG"E#192Ł^ tri~uoromethyl hypochlorite or per~uoro!t!butyl hypochlorite ð66JA3083\ 67IC1062\68JA4838\ 70JA395\ 75IC164Ł^ and tri~uoromethaneperoxysulfonic acid ð72CB0512Ł[ Examples of theoxidation products are the structures "21#Ð"24#[ When "24# was heated with chlorine ~uoride\ it wastransformed into the open chain compound F2CSO1CF1SF3Cl ð81CB424Ł[

O2S

SO2

F

FF

F

(32)

F4S

SF4

F

FF

F

(33)

S

S F

FF

F

OCF3F3CO

F3CO OCF3

(34)

F4S

SO2

F

FF

F

(35)


5[97[1[1[1 Dichloro\ dibromo\ and diiodo compounds

Halogenated 0\2!dithietanes result from the photochemical dimerization of chloro!~uorothiophosgene\ chlorobromothiophosgene\ and dibromothiophosgene ð65CB2321\ 66CB805\76CB0388Ł[ Tetrabromo!0\2!dithietane was also obtained from its tetrachloro analogue by sub!stitution using BBr2\ in 67) yield ð66CB805Ł[ These compounds\ along with tetrachloro!0\2!dithi!etane undergo various reactions at either carbon or sulfur\ in much the same way as tetra~uoro!0\2!dithietane ð22CB456\ 66CB805\ 72CB0512\ 76SUL48\ 77JFC"28#218Ł[ Some transformations of the parentdisulfone 0\0\2\2!tetraoxo!0\2!dithietane "25# are of interest] it can be halogenated by aqueouschlorine or bromine\ a}ording tetrachloro or tetrabromo disulfones in high yields "an analogousiodination does not occur#[ Chlorination was also e}ected using C3F8SO1Cl and Et2N[ The tetra!chlorodisulfone "26#\ upon mild hydrolysis\ was converted quantitatively into the sulfonic acid "27#"Scheme 09#[ Trichloro disulfone "39# was obtained from the silylated disulfone "28# upon treatmentwith butyllithium and C3F8SO1Cl:Et2N "Equation "4## ð72CB0174\ 74CB1197Ł[ Treatment of dibro!mothiophosgene "Br1C1S# with ozone at −79>C resulted in its partial trimerization^ hexabromo!0\2\4!trithiane was formed in 4) yield ð66CB805Ł[

O2S

SO2

SO2

O2SCl

Cl Cl

Cl ClO2S SO3H

Cl Cl Cl

Cl2/H2O, RT

88%

H2O, 40 °C

(36) (37) (38)

Scheme 10

O2S

SO2

SO2

O2SCl

Cl

i, BuLiii, C4F9SO2Cl/Et3N

(39) (40)

TMS TMS Cl (5)

Bis"halogenated# open chain èm!disulfones exist for all four halogens^ some have been knownsince the end of the nineteenth century\ for example Br1C"SO1Et#1 ð0789CB2115Ł[ They may beproduced by direct chlorination or bromination of èm!disulfones using aqueous halogen^ sulfurylchloride or sulfuryl bromide may also be used ð24JA106\ 62JOC2247\ 64CJC1553\ 64JOC0167\ 79CJC0885\77ZOR0216Ł[ The trisulfone of 0\2\4!trithiane has been fully chlorinated photochemically\ whiletrithiane itself can be converted directly into the same product\ that is\ hexachloro!0\0\2\2\4\4!hexaoxo!0\2\4!trithiane "30#\ when heated with aqueous chlorine and MoO2 ð52JPR0\ 53ZC346Ł[ Aninteresting transformation of this trisulfone occurred when it was heated with SbF2 and catalyticamounts of SbCl4 in sulfolane\ resulting in the isolation of "31#[ The hexabromo analogue of "30#gave the tetrabromo analogue of "31# under milder conditions\ in dioxaneÐwater[ With tertiaryamines or phosphines\ these trisulfones a}orded stable salts such as "32# "Scheme 00# ð75CB2520Ł[Under certain conditions*when 0\2\4!trithiane is treated with sodium hypochlorite in an alkalineenvironment*chlorination occurs\ but oxidation stops at the disulfone stage and "33# is producedð45JCS497Ł[ When treated with a tertiary amine\ the monosulfone of hexachloro!0\2\4!trithiane wasconverted to "34# ð57USP2265203Ł[

Et3N

(43) (41)

SbF3/SbCl5, sulfolane, 190 °C

O2S SO2

O2S Cl

Cl

Cl

Cl Cl

–

Et3NH+O2S SO2

O2S

Cl

Cl

Cl Cl

Cl

Cl

O2S SO2

Cl Cl

Cl Cl

(42) 62%

Scheme 11

The potassium salts of monohalogenated èm!disulfones have also been halogenated "Equation"5## ð62JOC2247Ł[ Phenyliodonium ylides undergo brominolysis\ a}ording dibromo!èm!disulfonesð89CC0348\ 80CC369Ł[ Alternatively\ the halosuccinimides NCS\ NBS and NIS give the correspondingdihalodisulfones "Equation "6## ð77JCR"S#295Ł[ Chlorination of a methylene group in some sulfonesbearing another sulfur!containing group has been e}ected by aqueous chlorine in acetic acid^ in

144Two Chalco`ens

(44)

O2S SO2

O2S

Cl

Cl

Cl Cl

Cl

Cl

(45)

S

SO2

Cl

ClCl

Cl

some cases further transformations led to the isolation of interesting products\ as depicted in Scheme01 ð45JCS497\ 64CJC1553\ 79CJC0885\ 72CJC509\ 80CJC1016Ł[ N!Chlorosuccinimide and sulfuryl chloridewere used in order to convert H1C"SO1Cl#1 into Cl1C"SO1Cl#1 ð65CZ280Ł[

F3CSO2

F3CSO2

Y– K+X2, CCl4

F3CSO2

F3CSO2Y

X

X = Y = BrX = Y = Cl

(6)

(7)CH2Cl2, RT

NI

O

O

PhI

SO2Ph

SO2Ph

SO2Ph

SO2Ph

I

I2+

79%

Cl2, AcOHMeSO2CH2SH or MeSO2CH2SO2OPh MeSO2CCl2SO2OPh

Cl2/H2O

AcOHMeSO2CH2SCH2Ph MeSO2CCl2SO2Cl

NaOCl4-ClC6H4SCH2SO3Na 4-ClC6H4SO2CCl2SO3Na

Scheme 12

The transformation of a thiocarbonyl group into CCl1 can be achieved by chlorination[ Oneexample involved photochemical addition of chlorine to carbon disul_de^ the dichloromethanebis"sulfuryl chloride#\ Cl1C"SCl#1\ formed initially was used for the preparation of the heterocycle"35# "Scheme 02# ð89JCS"P0#498Ł[ In another example\ the heterocycle "36# was heated in a sealedtube with PCl4 and was converted directly into "37# "Equation "7## ð80CB1914Ł[

TMS-N=S=N-TMSClS SCl

ClClCS2

Cl2

hν

N

S S

NS

Cl Cl

56%

Scheme 13(46)

PCl5

∆S

SF3C

F3C

SS

SF3C

F3CCl

Cl

(47) (48)

(8)

5[97[1[2 Two Halogens\ an Oxygen\ and a Sulfur Function

Only one compound of this type is known[ It was obtained from the addition of chlorine to eitherMeOC"S#SMe or MeOC"S#SSC"S#OMe\ both of which a}orded the same product\ MeOCCl1SClð42JA3471\ 45JA5969Ł[


5[97[1[3 Two Halogens and Other Chalcogen Functions

Tetra~uoro!\ tetrachloro!\ and tetrabromo!0\2!diselenetanes are known[ The ~uoro compound"49# was obtained by heating polymeric F1C1Se\ which in turn was formed from the boroncompound "38# "Scheme 03# ð65ZAAC"316#003Ł[ Treatment of "49# with BCl2 or BBr2 gave its tetra!chloro or tetrabromo analogues[ 0!Tri~uoromethyl!0\2\2!tri~uoro!0\2!diselenetane was formedfrom the interaction of "CF2CF1Se#1Hg and "CF2Se#1Hg\ followed by treatment with Et1AlIð80CB40Ł[ Two cyclic ethers*oxetane and tetrahydropyran "40#*were converted into "42# whentreated with the selenoxide "41# and acetic anhydride\ in a Pummerer!type reaction "Equation"8## ð82TL0200Ł[ Tetra~uoro!0\2!ditelluretane was obtained by thermolysis of Me2SnTeCF2\ whichinitially "at −085>C# gave the monomer F1C1Te ð81C67Ł[ The same compound "43# was producedfrom the reaction of Hg"TeCF2#1 with two equivalents of Et1AlI^ when the monomer F1C1Te wasallowed to react with F1C1Se\ tetra~uoro!0\2!selenatelluretane "44# was formed[ Compound "43#was converted into its tetrachloro analogue with BCl2 ð82JCS"D#1436Ł[

KF

∆

(49) (50)

B(SeCF3)3 Se

F

F

polymeric

Se

Se

F

F F

F∆

Scheme 14

(51) (53)

Ac2O, CH2Cl2

X = CH2 or (CH2)3

(52)

(9)O

X

F SePh

F

+

O

AcOCH2XOCF2SePh

(54)

Te

Te

F

F F

F

(55)

Se

Te

F

F F

F

5[97[2 TWO HALOGENS AND ONE CHALCOGEN FUNCTION

5[97[2[0 Two Halogens\ a Chalcogen\ and a Nitrogen Function

5[97[2[0[0 Oxygen compounds

Per~uoromethyleneimine "N!~uorocarbonimidic di~uoride# "45# is a good precursor for the prep!aration of several compounds in this category\ especially compound "47#\ through the addition ofFSO1OX "46# to its double bond "Equation "09##[ The related compound FSO1OCF1N"OSO1F#Fwas also obtained from "45# and the peroxide FO1SOOSO1F ð72IC794Ł[ However\ the reactionbetween F1C1NCl and FSO1OX led to the formation of a di}erent product\ that is\ the azocompound FSO1OCF1N1NCF1OSO1F ð73JOC2489Ł[ Other additions to the double bond of per!halogenated imines include the reactions in Scheme 04 ð65JA2418\ 72JOC3733\ 76AG"E#203\ 89JFC"37#284Ł[Some of these compounds were cyclized to form oxaziridines\ upon reaction with metal ~uoridesat a low temperature "Scheme 05# ð65JA2418\ 68IC808\ 79IC0229\ 72JOC3733Ł[ Direct epoxidation ofper~uoroazaalkenes is not normally possible\ except with F1C1NCF2 which\ with mcpba\ gave thecorresponding oxaziridine in 49) yield ð82JOC3643Ł[

NF

F

F+ FSO2OX FSO2OCF2NFX (10)

(56) (57) (58)X = F, Cl, Br

Oxaziridine "48# underwent cycloaddition reactions with tetrahalogenated ethylenes and also withmethyl ketones\ a}ording _ve!membered heterocycles such as "59# and "50# "Scheme 06# ð71JA3923\

146One Chalco`en

NCl

Cl

Cl

NCF3

F

F

NCF2CFClX

F

F

F5SOCCl2NCl2

+ F3COOH

F5SOCl

F3COOCF2NHCF3

+

+

NCF3

F3CCH2O

(CF3)2NX = F, Cl or Br

+ 2 ClF

F3COOCF2NHCF2CFClX

(CF3)2NCF2OCH2CF3

F3COOH

–F3CNCl2

Scheme 15

Scheme 16

F3COOCF2NHCF2CFClXKHF2, –196 °C

NaF, –196 °C

N

OF

FX

FCl

F F

N

OF

FCF3

F3COOCF2NHCF3

NSF5

F

F i, F3CO2Hii, NaF

N

OF

FSF5

75JOC3355Ł[ The per~uoro oxazolidine "59# was also formed in low yield upon pyrolysis of per!~uoromorpholine ð54JCS5966Ł[ The same compound and some related per~uoro!0\2!oxazolidines"51#Ð"53# were produced electrochemically from various precursors ð45JA4526\ 47JA0778\ 89JFC"37#146Ł[The potassium and caesium salts of F1NCF1OH have been formed upon reaction of di~uo!roaminocarbonyl ~uoride "F1NCOF# with KF or CsF ð56IC0600Ł[

Scheme 17

N

OF

FCF3

F

F X

Y

RCOMe

(59)

N

O

F3C

F

F F

F

XY

N O

O

F3C

F

F R

(60)

(61)

X, Y = halogens

N

O

F3C

F

F F

F

FCF3

(62)

N

O

F3C

F

F N(CF3)2

F

FF

(63)

N

O

F5C2

F

F F

F

FF

(64)

5[97[2[0[1 Sulfur compounds

Some unusual reactions have been reported with thiocyanates and ~uorine[ Methyl thiocyanatewas converted into F4SCF1NF1 when heated with elemental ~uorine ð48JA2488Ł[ Potassium or silver


thiocyanate in the presence of catalytic amounts of CaF1 gave\ among several other products\FSCF1NF1 ð54ZOB0301Ł[ An interesting conversion of compound "54# occurred upon its treatmentwith triethylamine\ when the zwitterion "55# was obtained "Equation "00## ð89AG"E#59Ł[ The anal!ogous reaction between "56# and quinuclidine "57# resulted in the formation of another zwitterion\"58# "Equation "01## ð78AG"E#110Ł[

O2S

SO2

F

FF

F

(65)

+ 2 Et3NTHF, –70 °C

2 Et3N+CF2SO2–

(66)

(11)

S

SO2

F

FF

F

(69)

+

(67)

N N CF2SCF2SO2– (12)

+

(68)

Addition of chlorine to "69# gave "60#[ Upon heating this was converted into a mixture ofheterocycles "61# and "62# "Scheme 07# ð60CB1621Ł[ Compound "61# was converted by Hg"SCF2#1into F2CSSCF1NCS\ while "69# added photochemically F2CSCl to a}ord F2CSSCFCl "NCS#[

(70) (72)(71)

70 °CF

S

NCS NCS

SClF

Cl

N

SS Cl

FF N

SS Cl

ClClCl2

+

(73)

Scheme 18

5[97[2[1 Two Halogens\ a Chalcogen\ and Other Functions

Per~uoro!1!phosphapropene\ F2CP1CF1\ when added to methanol forms F2CPHCF1OMe^C1F4P1CF1 reacts similarly ð75ZN"B#038\ 89ZN"B#037Ł[ The sul_nic salt "64# was obtained from "63#and sodium sul_te or sodium dithionite^ its oxidation with H1O1 gave the corresponding sulfonateand\ upon acidi_cation\ the free acid "Equation "02## ð78JA0662Ł[ A similar reaction occurred using"EtO#1P"O#CFBr1 and Na1S1O3 ð78CJC0684Ł[ The halogenated sulfones "65# were converted to "66#when their anion attacked PhHgCl "Equation "03## ð63JOM"60#224Ł[ Another organometallic mercurycompound\ HOHgCI1SO2Na\ was obtained from the reaction of HgO and CHI1SO2Na ð24CB0402Ł[

(74) (75)

+(EtO)2P Br

O

F F

Na2SO3(EtO)2P SO2Na

O

F F

(13)

(14)

(76) (77)X = Cl, Br

+ PhHgClPhSO2CHX2 PhSO2CX2HgPhButOK, THF, –60 °C

5[97[3 TWO HALOGENS AND TWO GROUP 04 ELEMENT FUNCTIONS

5[97[3[0 Two Halogens and Two Nitrogen Functions

5[97[3[0[0 Diamines and their derivatives

The simplest compound of this class is per~uorodiaminomethane "68#\ which can be prepared by~uorination either of cyanuric chloride "67# or of aminoiminomethane!sul_nic acid "79# "Scheme

148Two Group 04 Elements

08# ð54ZOB0301\ 55JOC3121Ł[ The C!monochloro analogue of "68#\ that is FClC"NF1#1\ was formedfrom per~uoroguanidine and ClNO1 ð67IZV375Ł[ Tetramethylurea was converted into "Me1N#1CF1

when treated with COF1 in the presence of NaF ð51JA3164Ł[ Fluorine or chlorine ~uoride adds tothe nitrile function in some per~uorocyanamides\ with the formation of perhalogenated methane!diamines\ as illustrated in Scheme 19 ð89JA617\ 81IC377Ł[ Chlorine ~uoride has also been added tothe N1C bond of some halogenated imines\ in the presence of CsF^ for example\ "70# was convertedinto "71# "Equation "04## ð89JFC"37#284Ł[ A related addition of ClF occurred to the C1N bond of"73#\ which was obtained from "72# and LiORf "where Rf is a per~uoro group# "Equation "05##ð81JFC"46#182Ł[ When "73# "n�0\ Rf�C"CF2#1CH2# was treated with C5F4SiMe2 and CsF\ ~uorineat the sp1 carbon was replaced by the C5F4 group ð82IC3791Ł[

(78) (80)

F2, 125 °CN

N

N

Cl

Cl ClNF2

NF2F

F H2N SO2H

NHF2

(79)

Scheme 19

Scheme 20

(CF3)2N N

(CF3)2N N

F3CN(F) N

F2, CsF

ClF

ClF

(CF3)2NCF2NF2

(CF3)2NCF2NCl2

F3CN(F)CF2NCl2

ClF, CsF(CF3)2NCF2NCl(CF3)(CF3)2NC(F) NCF3

(81) (82)

(15)

(CF3)2NCF2N

(83)

F

F(84)

(CF3)2NCF2N

F(2–n)

(ORf)n

LiORf(16)

Insertion of alkenes and nitriles into the N0Cl bond of "71#\ as well as photolytic reactions ofthe latter with SF4Cl and CF2COCl\ occur readily ð89JFC"37#284Ł[ Several higher halogenated `em!diamines were produced in a similar way from "74# and halogenated alkenes which inserted into theN0Cl bond thermally^ for example "75# was obtained using CF11CClF "Equation "06## ð81IC377Ł[When photolyzed alone "75# formed the imine "72# in high yield^ in the presence of halogenatedalkenes\ insertion occurred and compounds such as "76# were formed "Scheme 10#[ Photolysis ofthe simpler N!chlorodiamine "71# led to the formation of the diazane derivative "77# "Equation"07##[ Compound "71# added to 0\0!di~uoroethylene and tri~uoroethylene on irradiation formingadducts such as "78# "Equation "08##[

(CF3)2NCF2NCl2

(85)F

F F

Cl(86)

∆(CF3)2NCF2N(Cl)CF2CCl2F (17)+

(83)(87)

F

F

CF2CCl2F

CH2CCl2F

(CF3)2NCF2N, hν

CF2CCl2F

Cl

(CF3)2NCF2Nhν, –CCl3F

N

F

F(CF3)2NCF2

(86)

Scheme 21


(82)

hν

(88)

CF3

Cl

(CF3)NCF2N (CF3)NCF2N(CF3)N(CF3)CF2N(CF3)2 (18)

(82)

(CF3)2NCF2N(CF3)CH2CClF2

CF3

Cl

(CF3)2NCF2N

(89)

hνF

F(19)+

Chlorine ~uoride has also been added to the C1N bond of a per~uorohydrazone^ the adduct\upon irradiation with UV light\ was converted into a complex tetrazane having two CF1 groups~anked by nitrogen functions ð78IC2234Ł[ A related per~uorohydrazone\ "89#\ added a methyl groupand ~uorine to its double bond upon reaction with iodomethane and silver ~uoride^ compound "80#was formed "Equation "19## ð81IC3806Ł[ Some di~uoromethylene `em!diamines with alkyl or phenylgroups are also known[ A `em!diamine with two phenyl groups\ PhNHCF1NHPh\ was preparedfrom PhNHCF2 and aniline ð48ZOB1058Ł[ The bis"azo compound# O1NC5H3N1NCF1N1NC5H3NO1 was the product from the reaction of di~uorodinitromethane with 3!nitroanilineð81IC218Ł[ The preparation of the nitramine F1NCF1NO1 from CF1"OF#1 and F1NC"F#1NF hasbeen described ð57USP2276922Ł[ A simple amine derivative\ di~uoro"bisisocyanato#methane "82#\ wasproduced upon thermolysis of "81# "Equation "10## ð73JOC3430Ł[ Some sulfur!containing aminederivatives have been reported\ derived from various simple compounds bearing a cyano group^some examples are illustrated in Scheme 11 ð56MI 597!90\ 57ZN"B#632\ 75CB096Ł[

(CF3)2NN(Me)CF2N(CF3)N(CF3)2

(90)

(CF3)2NN

(91)

F

N(CF3)N(CF3)2

MeI, AgF(20)

NN

O-TMSTMS-O

O-TMSTMS-O

F F NCO

NCOF

F

∆

(92) (93)

(21)

H2N NN N

SF2F2SF F

N NSF2F2S

F F

N NBr2F2SF F

N NSF2F2S

F F

N NCl2F2S

F F

OO

O

O

F2S(O)N N

F2SN N

Scheme 22

SF4

F2S(O)N N

F4SO

Br2, HgF2

F2S(O)N NCl2, HgF2

SF4

5[97[3[0[1 Dinitro compounds

Di"halo#dinitromethanes of the general formula X1C"NO1#1 are known with all four halogens^some mixed halogen compounds have also been reported[ Dichloro! and dibromodinitromethanesare formed in several degradative reactions of a variety of precursors "too many to mention in thespace available here# by nitric acid[ The conversion of 1\3\5!trichloro! and 1\3\5!tribromoanilineinto dichloro! and dibromodinitromethane\ respectively\ is an important preparative method


ð33JOC308Ł[ A more conventional method for the preparation of dibromodinitromethane involvedthe reaction of sodium dinitromethanide with bromine after treatment with butyllithium\ or directlywith bromine in THFÐHMPA "hexamethylphosphoramide# ð78ZOR1389Ł[ Phenyliodonium dinitro!methylide was converted in high yields into either dichloro! or dibromodinitromethane with theappropriate halogen\ NCS or NBS "Equation "11## ð67IZV1237Ł[ The very unstable diiodo!dinitromethane was reported to be formed upon acidi_cation of potassium iododinitromethanideð13JCS331Ł[ Di~uorodinitromethane "84# was _rst prepared from di~uorodiazirine "83# and N1O3

"Equation "12## ð53JHC122Ł[ The same substrate "83#\ which on photolysis generates di~uorocarbene\gave a 4) yield of "84# with NO^ the photochemical reaction of di~uorodiiodomethane in excessNO a}orded a 09) yield of "84# ð81IC218Ł[ The reactions of potassium trinitromethanide with~uorineÐsodium ~uoride and also with potassium ~uoride again led to the formation of "84#ð57IZV318\ 57JOC2962Ł[ Di~uorodinitromethane was also formed in 27) yield from the reactionof di~uoronitroacetic acid with XeF1^ in a similar way\ ~uorochloronitroacetic acid produced~uorochlorodinitromethane ð77IZV355\ 77IZV1528Ł[ The same compound was obtainedwhen chlorotrinitromethane was treated with CsF in DMF ð69IZV1442Ł[ Chlorobromodinitro!methane was prepared from chlorine and ammonium bromodinitromethanide^ the latter was formedfrom dibromodinitromethane in liquid ammonia "Equation "13## ð33JOC308Ł[

PhI

NO2

NO2

+ X2 or NX

O

ONO2

NO2X

X(22)

X = Cl, Br

+ N2O4

NO2

NO2F

F(23)

N

NF

F

hν, –N2

(94) (95)

NO2

NO2Br

ClNH4

+

NO2

NO2Br

Br NO2

NO2

Br (24)Cl2–

NH3

5[97[3[0[2 Cyclic compounds

Several methods have been developed for the preparation of the important heterocycle di~uo!rodiazirine "83#[ Historically\ the _rst method involved cyclization of F1C"NF1#1 by ferroceneð55JHC134Ł[ The same substrate was converted more e.ciently into "83# using tetrabutylammoniumiodide "Scheme 12# ð56JOC0833\ 57JOC0736Ł[ Tetra~uoroformamidine "85# was also transformede.ciently into "83#\ using either ferrocene or potassium iodide ð56JOC3934\ 57JOC0736Ł[ Tetra~uoro!formamidine was isomerized by potassium ~uoride at a low temperature to per~uorodiaziridine"86#\ an unstable compound which frequently exploded] with ferrocene this gave "83#^ when heatedwith caesium ~uoride it dimerized to form "87# "Scheme 13# ð57JOC2378Ł[ Curiously\ compound "87#was claimed in a patent to be a possible heat transfer ~uid ð81JAP93009272Ł[ A unique rearrangementleading to the formation of "83# occurred when di~uorocyanamide "F1NCN# was treated withcaesium ~uoride at room temperature ð55IC0344Ł[ Chloro~uorodiazirine was obtained from di!chlorobis"di~uoramino#methane\ Cl1C"NF1#1\ after treatment with boric acid^ the precursor wasprepared from per~uoroguanidine\ HCl and HNO2 ð56JOC0833\ 56USP2244381Ł[ Some further per!halogenated diaziridines are compounds "88#Ð"091#[ Their preparation involved the use of CsF orKF as catalysts at low temperatures[ Compound "88# was obtained from CF11NF orCF2N"F#C"F#1NF ð72JOC660Ł[ Compound "099# was formed from CF11NCl^ on treatment withmercury in tri~uoroacetic acid\ chlorine was replaced by hydrogen ð73JOC2489Ł[ Compound "090#was formed from CF11NF and CF11NBr\ which _rst gave CF2N"F#C"F#1NBr ð77JOC3332Ł[Compound "091# was prepared from CF11NF and CF11NCF2 ð89JA617Ł[

Fluorine and chlorine*from either ClF or a mixture of chlorine and mercury di~uoride*readilyadd to cyanuric ~uoride "092# a}ording compound "093# "Equation "14## ð64MI 597!90\ 75CB096Ł[Fluorine added to "092# in a complex way^ in addition to the per~uoro analogue of "093#\ per~uoro!


(96)(94)

NF2

NF2F

F

F

F N

N NF

F NF2

Bu4N+ I–

100%

KF, MeCN/H2O

100%

Scheme 23

(96) (97)

F

F N

NNF

F NF2

KF, –160 °C CsF, dimer

F

F

F

F2N N

N

F

NF2FF

Scheme 24

(98)

(99)

F

F N

N

F

CF3

(100)

F

F N

N

Cl

CF3

(101)

F

F N

N

Br

CF3

(102)

F

F N

N

CF3

CF3

0\2!diazolidine and noncyclic compounds such as CF2N"F#CF1N"F#CF2 were formed ð51JA1640Ł[Per~uoro!1\4!diazahexa!1\3!diene "094#\ when heated with CsF\ was cyclized to a mixture of isomeric0\2!diazolines "095# and "096#[ In acetonitrile in the presence of CsF\ both products gave the anion"097#\ which reacted with alkyl halides a}ording N!alkyl compounds\ for example "098# withiodomethane[ Compounds "097#\ "095# and "096# also underwent ~uoride ion induced reactions withper~uoroalkenes^ the main product\ when per~uorocyclopentene was used was "009# "Scheme 14#ð74JCS"P0#0080Ł[ The per~uoro analogue of "098# was converted to 1\1!dichloro! or 1\1!dibromo!dimethyl!0\2!diazolidine ð73JFC"13#346Ł[ Another heterocycle "001#\ was formed from "000# uponheating with CsF^ when irradiated in the presence of CsF\ "000# was transformed into a complexdimer "Equation "15## ð89HAC056\ 81ICA416Ł[ Compound "001# was also formed upon dimerizationof "095# and "096# ð74JCS"P0#0080Ł[

(103)

N N

NF F

F

(104)

N N

N

Cl

Cl Cl

F

Cl F

Cl

F Cl

ClF or Cl2 + HgF2(25)

F3CNNCF3

F

F

N NF3C

F

FF F

F

N NF3C

FF

F F

F

+CsF, 220 °C

(105) (106) 65% (107) 16%

MeCN, F–

N N–F3C

FF F

F

F F

MeI

F

F

FF

F

F F FN NF3C

FF F

F

F F

F

F

FFF

N NF3C

FF F

F

F F

Me

(110) (108) (109)

Scheme 25


NCClF2

F

F

NCClF2CsF, 110 °C N NF3C

FF F

F

F F N

N CF3

(111)F

F

FF

(112)

(26)

5[97[3[1 Two Halogens and Two Phosphorus Functions

5[97[3[1[0 Bis"phosphonates#

The study of these compounds has been intensi_ed since two important discoveries were made]"i# the ability of Cl1C"PO2H1#1 "clodronic acid\ "004## to help in the process of bone formation^ and"ii# the various physiological properties of nucleotide analogues\ especially ATP\ in which an oxygenatom in the triphosphate unit is replaced by a di~uoromethylene group ð67JCE659\ 73JCS"P0#0008Ł[Bis"halogenated# methylenebisphosphonic acids are usually prepared through halogenation of theappropriate tetraesters\ which are subsequently hydrolyzed[ The ester Cl1C"PO"OEt#1#1 was obtainedin 61) yield by heating H1C"PO"OEt#1#1 with PCl4 at 039>C ð59ZOB0591Ł[ However\ the cheapercommercially available isopropyl tetraester "002# is the preferred starting material[ This was con!verted into its dichloro derivative "003# and then hydrolyzed to the acid "004# by heating inconcentrated hydrochloric acid "Scheme 15# ð55BEP561194\ 57JOM"02#088\ 74JOM"180#034Ł[ The dibromoanalogues and the relatively unstable diiodo analogues of "003# were prepared in a similar way bythe hypohalite method ð60JOC0724Ł[ Several other tetraesters "symmetrical or mixed# of the generalformula X1C"PO2R1#1 "where R was an alkyl group and X was chlorine or bromine# were preparedby the hypohalite method^ in which careful control of temperature\ pH\ and reaction time led tohigh yields ð81JCS"P1#724\ 81PS"69#072Ł[ The ester "003# was also converted to the acid "004# withouthydrolysis by heating in sym!tetrachloroethane\ with evolution of propene ð56JOC3000Ł[ Since thisacid is highly polar\ it was desirable to prepare some partial ester derivatives[ This was achieved viatwo methods] silyl derivatives and selective hydrolysis[ The _rst method was based on the obser!vations that the rate of silylation of methyl!containing mixed tetraesters follows the order methyl×primary alkyl×secondary alkyl\ whereas the hydrolysis rate of silyl and alkyl esters follows theorder SiMe2×tertiary alkyl×secondary alkyl×primary alkyl[ Taking into account these factors\the preparation of several tri!\ di!\ and mono!esters was e}ected[ For example\ the ester "005# wasconverted _rst to "006# and then to the salt "007# in 76) yield "Scheme 16#[ The second approachwas suitable for n!alkyl esters\ since branched chain alkyl groups in acidic conditions undergohydrolysis faster than n!alkyl groups[ Thus\ "008# was transformed into "019# in 33) yield "Scheme17# ð82TL3440Ł[

P(OPri)2

P(OPri)2

O

O

P(OPri)2

P(OPri)2

O

O

P(OH)2

P(OH)2

O

O

Cl

Cl

Cl

Cl

Scheme 26

i, Na/tolueneii, Cl2 or NaOCl HCl

∆

(113) (114) (115)

P(OPri)2

P

O

TMS-Cl, NaI, MeCN

∆

MeOH, NaOH

(116)

OOPri

OMe

Cl

Cl

P(OPri)2

P

O

(117)

OOPri

O-TMS

Cl

Cl

P(OPri)2

P

O

(118)

OOPri

ONa

Scheme 27

Cl

Cl

Di~uoro tetraesters\ as well as the free bisphosphonic acid "011# which is an isopolar analogue ofpyrophosphoric acid\ were prepared by several routes[ Fluorination of "010# with perchloryl ~uoride


P(OPri)2

P(OHex)2

O i, MeSO3H, toluene, ∆ii, NaOH

(119) Hex = n-C6H13

O

Cl

Cl

P(ONa)2

P(OHex)2

O

(120)

O

Cl

Cl

Scheme 28

in a strongly basic environment gave "011# in good yields "R�Et or Pri#^ this was converted withtrimethylsilyl bromide into the silyl derivative "012#\ which then was hydrolyzed to the free acid"013#\ isolated as its trisdicyclohexylammonium salt "Scheme 18# ð70JOC3462\ 71JFC"19#506Ł[ Acetylhypo~uorite was also an e.cient ~uorinating agent ð80BMC246Ł[ Coupling reactions have also beenused^ for example\ the lithium salt obtained from HCF1P"O#"OEt#1 and lithium diisopropylamide"LDA# gave\ on reaction with "EtO#1P"O#Cl\ the tetraester "EtO#1P"O#CF1P"O#"EtO#1 in 63) yieldð71TL1212Ł[ The reaction between BrF1CPO"OPri#1 and "PriO#1PONa also gave "011# "R�Pri#ð70CC829Ł[ The same compound was formed using CBr1F1 and "PriO#1PONa^ the mixed halogentetraester FBrC"PO"OPri#1#1 was obtained from FCH"PO"OPri#1#1 and tetraisopropyl pyro!phosphate\ upon treatment with bromine in aqueous K1CO2 ð77JOM"239#82Ł[ The application of theMichaelisÐBecker variation to the preparation of di~uoromethylene esters has also been describedð79JFC"04#152\ 71JFC"19#010Ł\ as have other routes to compounds of this type ð83JOC1282Ł[

P(OR)2

P(OR)2

O

FClO3, ButOK

(121)

O

P(OR)2

P(OR)2

O

(122)

O

F

F

TMS-Br H2OP(O-TMS)2

P(O-TMS)2

O

(123)

O

F

F

P(OH)2

P(OH)2

O

(124)

O

F

F

Scheme 29

Coupling of X1C"PO2H1#1 with 4?!phosphoromorpholidate of adenosine resulted in the formationof "014# ð73JCS"P0#0008Ł[ In the same way\ the CF1 analogue of 2?!azido!2!deoxythymidine tri!phosphate was obtained ð80BMC246Ł[ Other nucleotide analogues with a CF1 group in the place ofan oxygen next to the _rst phosphorus atom\ of the general formula "015#\ were prepared from thetris"tetrabutylammonium# salt of F1C"PO2H1#1 and the tosylate of the nucleoside^ these initiallygave the CF1 pyrophosphate analogues\ which were converted with phosphate into "015# ð80TL5314Ł[Isopentenyl and geranyl di~uoromethylenephosphonates and some nucleotide analogues were alsoprepared using this methodology ð75JOC3657\ 76JA4431\ 76JOC0683Ł[

O

OHHO

adenineO

PO

PHO3P

XX O

OH

O

OH

(125)X = F, Cl

O

HO

baseO

PPO

HO3P

OH OH

(126)

F

F

O O

5[97[3[1[1 Cyclic compounds

Reaction of the ylides "016# with triphenylphosphine led to the formation of diphosphiranes "017#"Equation "16## ð79IJC"B#509Ł[ Similar compounds "029# were obtained stereospeci_cally from trans!diphosphene "018# and dichloro! or dibromocarbenes "Equation "17## ð76T0682Ł[ Yields becamequantitative when sonication was applied ð80TL4854Ł[ Bis"tri~uoromethyl#phosphine "020#\ upontreatment with ZnMe1 or triethylamine\ was converted via F2CP1CF1 to 0\2!diphosphetane "021#"Equation "18## ð61CC562\ 72IC1462\ 74PS"10#238Ł[ Thermolysis of Me2SnP"CF2#1\ however\ was moree.cient^ this initially gave F2CP1CF1\ which was found to be fairly stable[ Depending on the


conditions\ the thermolysis products could be either F2CP1CF1 or "021# "a mixture of cis and transisomers#\ along with some trimer\ that is\ 1\3\5!tris"tri~uoromethyl#!0\2\4!triphosphorinð73AG"E#609Ł[ Similar thermolysis at 9[990 torr "9[02 Pa# of Me1NP"SnMe2#CF2 resulted in theformation of the monomer Me1NP1CF1\ which underwent polymerization^ when the polymerwas heated at 499Ð599>C\ the dimeric compound "022# was formed ð81ZN"B#210Ł[ Treatment ofCl1PCHCl1 with triethylamine led to the formation of "023# via ClP1CCl1 ð70ZOB1529Ł[Another heterocycle "024# was formed from the reaction of Cl1P"S#CF1P"S#Cl1 and butylamineð76CZ065Ł[

(127)X = Cl, Br

Ph3P

X

X

+ – + PPh3Ph3P

Ph3P

X

X

(128)

(27)

(28)

(129)

Ar = 2, 4, 6-But3C6H2

X = Cl, Br

+CHX3P

P

X

X

(130)

Ar

Ar

KOH+P P

Ar

Ar

(29)2 (CF3)2PH

(132)

Et3N, – 2HF

(131)

P

P

F

F

F

F

F3C

CF3

(133)

P

P

F

F

F

F

Me2N

NMe2

(134)

P

P

Cl

Cl

Cl

Cl

Cl

Cl

P

P

N

F

F

Cl

Cl

(135)

But

5[97[3[1[2 Miscellaneous compounds

When Me2GePMe1 was heated in benzene with Hg"CF2#1\ a mixture of products was formed\including Me1PCF1PMe1 ð67BSF"1#250Ł[ Both isomeric 0\2!diphosphetanes "021# reacted with meth!anol "the cis isomer reacted faster#\ a}ording F2CP"OMe#CF1P"CF2#CHF1 and other products offurther methanolysis ð74IC037Ł[ The chlorophosphine Cl1PCHCl1\ when heated with triethylamineand PCl2\ was transformed into Cl1PCCl1PCl1 ð70ZOB1529Ł[ The monomeric F1C1PCF2 reactedwith several dialkylphosphines forming "025#\ which upon heating with elemental sulfur a}orded"026# "Scheme 29# ð89ZN"B#188Ł[ Compound "027# was converted into several derivatives\ as illus!trated in Scheme 20 ð76CZ065Ł[ Carbon vapour reacted with PCl2 forming Cl1PCCl1PCl1ð69JCS"A#20Ł[ Some chlorinated and ~uorinated bis"phosphoranium# salts of the general formulaR2P¦C−"X#P¦R2X− are formed in solution when phosphines are treated with CCl3\ CFCl2\ orCFBr2 ð66S588\ 77JOC255Ł[

(136)

PCF3

F

F+ R2PH

'S'R2PHCF2PHCF3 R2P(S)CF2PHCF3

(137)

Scheme 30


Scheme 31

Cl2PCF2PCl2

F2PCF2PF2

(138)

Cl2P(S)CF2P(S)Cl2

(NMe2)2PCF2P(NMe2)2

(PriO)2P(S)CF2P(S)(OPri)2 PriOH

TMS-NMe2

SbF3

PhPCl2

5[97[3[2 Two Halogens and Two Other Group 04 Element Functions

The sole compounds in this category are "039# and "030#\ which were obtained upon thermolysisof "028# "Equation "29## ð73AG"E#609Ł[

(140)

Me3SnAs(CF3)2∆

As As

FF

F F

CF3F3C

cis and trans

As

As

As

FF

F

FF

F

CF3F3C

CF3

(30)+

(141)(139)

5[97[4 TWO HALOGENS AND ONE GROUP 04 ELEMENT FUNCTION

5[97[4[0 Two Halogens\ a Phosphorus\ and a Metalloid or Metal Function

When reacted with butyllithium in THF solution\ diethyl trichloromethylphosphonate "031# givesthe salt "032# which can be converted into "033# upon treatment with trimethylsilyl chloride "Scheme21# ð62JOM"48#126Ł[ The same salt "032# was formed from diethyl chloromethylphosphonate upontreatment with butyllithium and then CCl3 ð64S424Ł[ The di~uoro analogue of "032# was similarlyobtained in situ from diethyl di~uoromethylphosphonate and LDA[ With TMS!Cl this a}ordedTMS!CF1P"O#"OEt#1 in 76) yield\ while with Bu2SnCl the phosphonate Bu2SnCF1P"O#"OEt#1 wasobtained in 66) yield ð71TL1212Ł[ The salt LiCF1P"O#Ph1 was formed in situ from HCF1P"O#Ph1

and LDA ð89TL4460Ł[ Several compounds with a P0Ge bond\ mainly germylphospholanes\ under!went CF1 insertion into this bond^ the mildest way to produce di~uorocarbene was the thermaldecomposition of Hg"CF2#1 in benzene ð67BSF"1#250Ł[ Upon reaction with metallic cadmium thephosphonate "034# was converted into the stable salts "035# and "036# "Equation "20## ð70JFC"07#086Ł[The same phosphonate "034# reacted similarly with metallic zinc to a}ord BrZnCF1P"O#"OEt#1^after several days in contact with PhHgCl\ this gave another stable organometallic compound\PhHgCF1P"O#"OEt#1 ð78JOC502\ 89JFC"38#64Ł[ The related compound PhHgCCl1P"O#"OMe#1 wasformed from PhHgCCl1Br and P"OMe#2 ð55JOM"4#074Ł[ The stable copper compounds BrM!CuCF1P"O#"EtO#1 "M�Cd\ Zn# were produced from the corresponding cadmium or zinc phos!phonates and CuBr ð81T078Ł[ A stable rhodium complex containing the group PCF1P has beendescribed ð89JOM"288#078Ł[

(143) (144)(142)

Cl3C P(OEt)2

O

P(OEt)2

OCl

Li

Cl P(OEt)2

OCl

TMS

Cl

Scheme 32

BuLi, THF, –80 °C TMS-Cl, –80 °C

(146) (147)(145)

P(OEt)2

O

P(OEt)2

OF

BrCd

FCd

F

Br

F +P(OEt)2

OF

F

(31)P(OEt)2

OF

Cd

F

156Two Metalloids

5[97[5 TWO HALOGENS AND TWO METALLOID FUNCTIONS

5[97[5[0 Two Halogens and Two Silicon Functions

The chemistry of these compounds is dominated by the work of G[ Fritz on carbosilanes^ mostof his results have been summarized in a book and a review article ðB!75MI 597!90\ 76AG"E#0000Ł[

5[97[5[0[0 Linear carbosilanes

A simple compound of this class is perchloro!0\2!disilapropane "037#\ which was obtained byphotochlorination of the main product resulting from the reaction between chloroform and elemen!tal silicon in the presence of copper ð47CB11Ł[ It was also produced by photochlorination ofCl2SiCH1SiCl2 ð46IZV088\ 53CB0562Ł[ Perchloro!0\2!disilapropane "037# readily replaced one or moreof its silicon!bound chlorine atoms^ for example\ upon treatment with SbF2 or ZnF1 it was convertedto "038# ð53CB0562\ 60AG"E#409\ 61ZAAC"280#108Ł[ Further transformations were e}ected with LiAlH3]to "049# and to "040# "the latter with one equivalent of MeMgCl# "Scheme 22# ð60ZAAC"271#8\60ZN"B#379Ł[ Interestingly\ MeLi methylated exclusively the carbon atom of compound "037#[ Incontrast\ the reaction of "049# with MeLi was very complex\ the major products being MeH1SiCCl1SiH2 and CCl1!containing 0\2\4!trisilapentanes[ The reaction of "049# with MeMgCl wassimilarly complex^ however\ in the presence of a great excess of MeMgCl\ the main product wasTMS!CH1SiHMe1 ð67ZAAC"330#014Ł[ Photobromination of Cl2SiCH1SiCl2 by BrCl readily a}ordedCl2SiCBr1SiCl2 ð65ZAAC"308#102Ł[ A well!studied compound related to "037# is "042#^ it has beenprepared by several methods[ One method was by reaction of "038# with MeLi ð60ZN"B#379Ł[ Anotherapproach involved lithiation of dichloromethane "two equivalents of BuLi# and subsequent reactionwith trimethylsilyl chloride ð56JCS"C#0369\ 61JOC1551Ł[ Alternatively\ the lithiated "041# a}orded "042#\again with TMS!Cl "Scheme 23# ð69JOM"12#250Ł[ A better yield was achieved upon insertion ofdichlorocarbene into the Si0Si bond of "043#[ The dibromo analogue at the central carbon of "042#was prepared from TMS!CBr1Li and TMS!Cl\ and also from the complex TMS!BrP"NEt1#2 andTMS!Br ð69JOM"13#536\ 69TL3582\ 89ZOB698Ł[

Scheme 33

ZnF2

LiAlH4

MeMgCl

Cl3Si SiCl3

Cl Cl

(148)

F3Si SiF3

Cl Cl

(149)

H3Si SiH3

Cl Cl

(150)

Cl3Si SiMeCl2

Cl Cl

(151)

TMS-Cl CHCl3/KOH, 18-crown-6

61%

TMS Li

Cl Cl

(152)

TMS TMS

Cl Cl

(153) (154)

TMS TMS

Scheme 34

Partially chlorinated 1\1!dichloro!0\2!disilapropanes such as "044# and "045# were also obtainedfrom "041# and Me1SiCl1 or MeSiCl2 "Scheme 24# ð68ZAAC"337#44Ł[ Starting with PhMe1SiCCl1Li\similar compounds were also formed[ A di}erent method is also accessible for such compounds^for example\ Cl2SiCCl1SiMeCl1 was obtained through methylation of "Cl2Si#1CCl1 with MeMgClð60ZN"B#379Ł[ Full methylation of "038# at the silicon resulted in the formation of "042#[ Apartfrom halogenated silapropanes\ some related 0\2\4!trisilapentanes were also studied[ Photochemicalchlorination of "046# produced "047#\ which reacted further with ZnF1 and with MeMgCl in thesame manner as "037# "Equation "21## ð67ZAAC"328#050Ł[ Partial chlorination of "046# is also possible\using sulfuryl chloride and benzoyl peroxide ð60ZAAC"271#106Ł[ The most interesting reaction of"047# was methylation with MeMgCl] when MeMgCl was in large excess "07 ] 0#\ the main productswere TMS!C2C!TMS "36)# and CH11C"TMS#CH"TMS#1 "13)# ð63ZAAC"393#092Ł[ The same


reaction was studied with some ~uorinated silicon compounds such as F2SiCCl1SiF1CH1SiF2 andF2SiCCl1SiF1CHClSiF2 ð67ZAAC"328#050Ł[ An octahedral silicon complex has been described\ result!ing from the reaction between 1\1?!bipyridyl and "Cl2Si#1CCl1 ð89CB834Ł[

Scheme 35

MeSiCl3TMS SiMeCl2

Cl Cl

(155)

TMS Li

Cl Cl

(152)

Me2SiCl2 TMS SiMe2Cl

Cl Cl

(156)

SiCl Cl

(157)

Cl2, hνCl3Si SiCl3 SiCl Cl

(158)

Cl3Si SiCl3

ClCl ClCl

(32)

A fair number of di~uorocarbodisilanes are known[ Several disilanes of the general formula "048#and other related compounds reacted readily with di~uorocarbene\ produced by thermolysis ofMe2SnCF2^ the products "059# resulted from CF1 insertion into the Si0Si bond "Equation "22##[Some trisilanes also reacted in the same way[ For example\ FMe1Si"SiMe1#SiMe1F\ which wasconverted by single or double CF1 insertion to FMe1SiCF1SiMe1SiMe1F or "FMe1SiCF1#1SiMe1[Compound "059# "X�F# can react with Grignard and organolithium compounds "MeMgCl\ MeLi\PhLi\ etc[#^ one or both silicon!bound ~uorine atoms are then replaced by an alkyl or phenyl group\so that with MeLi either TMS!CF1SiMe1F or "TMS#1CF1 is obtained[ Other reactions at the Si0Fbond in "FMe1Si#1CF1 involved LiAlH3\ which converted it to "HMe1Si#1CF1\ and Me1PLi\ whichproduced Me1PMe1SiCF1SiMe1F as well as "Me1PSiMe1#1CF1 ð72AG"E#629Ł[

(159)

[CF2] XMe2Si SiMe2X

F F

(160)X = F, Cl, Br, OMe

(33)XMe2Si SiMe2X

5[97[5[0[1 Cyclic carbosilanes

Reaction of Cl2SiCH1CH1SiCl1CH1Cl with magnesium produced 0\2!disilacyclopentane "050#\which upon photochlorination eventually gave the fully chlorinated compound "051# "Scheme 25#[An interesting solvent e}ect was observed in the reaction of "051# with an excess of MeMgCl^ whilein ether several products were formed\ the main product "55) yield# being Cl1C1CClSiMe1CCl1!TMS\ in pentane\ compound "052# was formed exclusively ð69ZAAC"261#10\ 68ZAAC"347#26Ł[ WhenMeSiCl2 or Me1SiCl1 are heated at 699>C\ they are converted to the cyclic carbosilane "053#\ whichupon photochlorination a}ords the perchloro compound "054# "Scheme 26# ð59ZAAC"292#74Ł[ Thepartially brominated "055# was obtained from the photochemical reaction of "053# and brominechloride\ whereas the bromo analogue of "053# gave the octabromo analogue of "055# "Scheme 26#ð64ZAAC"308#102Ł[ The hexa~uoro analogue of "053# underwent photochlorination to produce amixture of 1\1!dichloro!\ 1\1\3\3!tetrachloro!\ and 1\1\3\3\5\5!hexachloro!hexa~uoro trisilacyclo!hexanes ð64ZN"B#854Ł[ The reactivity of these compounds is analogous to that already mentionedfor their linear analogues\ for example "054# was converted by LiAlH3 into 1\1\3\3\5\5!hexa!chlorotrisilacyclohexane ð60ZAAC"271#8Ł[ Unusual reactivity was\ however\ noted in the case ofMeMgCl^ with "054#\ four equivalents of MeMgCl gave the ring!contracted "056# in high yield[Further reaction of "056# with more MeMgCl a}orded several products\ the major being "057#"Scheme 27# ð62ZAAC"284#048\ 62ZAAC"288#179Ł[ Several partially chlorinated 0\2\4!trisilacyclohexanesare known\ some resulting from the interaction of "054# with its fully hydrogenated analogue\ thatis "H1SiCH1#2 ð60ZAAC"271#106Ł[ Their reactivity with MeMgCl is of interest\ since di}erent productsare obtained in each case depending on the structure of the substrate "Scheme 28#[ The reactivitiesof partly brominated trisilacyclohexanes with Grignard and organolithium compounds exhibit somesimilarity to and a number of di}erences from their chloro analogues^ the most notable di}erenceis the double substitution of carbon!bound bromine by butyl groups when butyllithium is used"Equation "23##[ Generally\ more results are available in the carbosilane _eld\ with ample discussionand mechanistic details ðB!75MI 597!90Ł[

158One Metalloid

(161)

Cl2, hνSiCl2Cl2Si

(162)

SiCl2Cl2Si

ClCl

ClClCl

Cl(163)

SiMe2Me2Si

ClCl

ClClCl

Cl

Scheme 36

MeMgCl

pentane

(166)

BrCl, hν

(164) (165)

hν, Cl2, CCl4, ∆

Si Si

SiClCl

Cl

ClCl

Cl

Si Si

SiClCl

Cl

ClCl

Cl

Si Si

Si

ClCl

Cl

Cl

Cl

Cl

Cl Cl

Cl

Cl

ClCl

Br Br

Scheme 37

(165)MeMgCl4MeMgCl SiCl2Cl2Si

ClCl

TMSCl

TMSSi

TMS

ClCl

ClCl

Scheme 38

(167) (168)

MeMgCl MeMgCl MeMgCl

Cl2Si

Si

SiCl2

Cl

ClCl

ClCl Cl

H2Si

SiH2

SiH2

ClCl

SiH2

SiH2H2SiCl

Cl Cl

Cl

Me2Si

SiH2

SiMe2

ClCl

Si

SiMe2Me2SiCl

Cl Cl

Cl

H Me

Scheme 39

SiMe2Me2Si

SiMe2

Me2Si

SiMe2

SiMe2

BrBr

Br

BrMe2Si

SiMe2

SiMe2

BuBu

Br

Br (34)BuLi

5[97[5[1 Two Halogens and Two Boron or Other Metalloid Functions

Two compounds of this type are known[ The _rst is Cl1BCCl1BCl1\ which was formed whencarbon vapour reacted with either BCl2 or B1Cl3 ð58JCS"A#0771Ł[ The other is Cl2GeCCl1GeCl2^ thiswas obtained in a similar way from carbon vapour and GeCl3 ð69JCS"A#20Ł[

5[97[6 TWO HALOGENS AND ONE METALLOID FUNCTION

5[97[6[0 Two Halogens\ a Silicon\ and a Metal Function

Apart from Grignard and organolithium compounds which exist only in solution "Section5[97[5[0#\ some stable compounds of this category are known with tin and mercury[ They are


normally formed from the appropriate organometallic compound coupled with metal or silylchlorides^ in one case\ an exchange reaction between organomercurials was noted[ Examples aregiven in Scheme 39 ð69JOM"12#250\ 69JOM"13#563\ 60JOM"16#08Ł[ Dichlorocarbene insertion into theSi0Hg and Si0Ge bond also occurs\ but the products are further transformed ð56JOM"6#P19Ł[

TMS Li

Cl Cl

TMS SnMe3

Cl Cl

TMS Li

Cl Cl

TMS HgCl

Cl Cl

+

+

Me3SnCl

TMS

Cl Cl

TMS

Cl Cl

+

Hg

TMS Li

Br Br

TMS SnMe3

Br Br

Me3Sn MgCl

Br Br

Me3Sn TMS

Br Br

TMS HgCl

Cl Cl

TMS HgPh

Cl Cl+

TMS

Cl Cl

TMS-Cl

Me3SnCl

TMS

Cl Cl

HgCl2 ++

Hg+ HgPh2HgPh2

Scheme 40

12–1

2–

5[97[7 TWO HALOGENS AND TWO METAL FUNCTIONS

Stable isolable compounds of this category involve tin[ Most were prepared by insertion ofdihalocarbenes\ from organomercurial precursors or chloroform "Equation "24## ð56JA1689\ 58JA0843\80SRI390Ł[ Coupling of Me2SnCBr1!TMS with Me2SnCBr1MgCl also produced "Me2Sn#1CBr1

ð69JOM"13#536Ł[ The theoretically interesting dilithiodi~uoromethane was shown by ab initio cal!culations to have a planar lithium bridged structure of CLi1F¦ F− ion pair character ð74CC4Ł[

R3Sn SnR3 + [CX2]R3Sn SnR3

X X(35)


6.09Functions Containing OneHalogen and Three OtherHeteroatom SubstituentsANGELA MARINETTI and PHILIPPE SAVIGNACDCPH - Ecole Polytechnique, Palaiseau, France

5[98[0 ONE HALOGEN AND THREE CHALCOGENS 161

5[98[0[0 One Haloèn and Three Oxyèn Functions 1615[98[0[1 One Haloèn\ Sulfur\ and Oxyèn Function 162

5[98[0[1[0 One haloèn and three sulfur functions 1625[98[0[1[1 One haloèn\ two sulfur\ and one oxyèn function 165

5[98[0[2 One Haloèn\ Selenium\ and Sulfur Function 165

5[98[1 ONE HALOGEN AND TWO CHALCOGENS 166

5[98[1[0 One Haloèn\ Two Chalcoèns\ and a Nitroèn Function 1665[98[1[1 One Haloèn\ Two Sulfur\ and a Phosphorus Function 1675[98[1[2 One Haloèn\ Two Sulfur\ and a Metal Function 167

5[98[2 ONE HALOGEN AND ONE CHALCOGEN 168

5[98[2[0 One Haloèn\ One Chalcoèn\ and Two Group 04 Elements 1685[98[2[0[0 One haloèn\ one oxyèn\ and two nitroèn functions 1685[98[2[0[1 One haloèn\ one sulfur\ and two nitroèn functions 1705[98[2[0[2 One haloèn\ one chalcoèn\ and two phosphorus functions 170

5[98[2[1 One Haloèn\ One Sulfur\ and Two Silicon Functions 171

5[98[3 ONE HALOGEN AND THREE GROUP 04 ELEMENTS 171

5[98[3[0 One Haloèn and Three Nitroèn Functions 1715[98[3[0[0 Halotrinitromethanes 1715[98[3[0[1 Miscellaneous halonitromethanes 1735[98[3[0[2 Halotriaminomethanes 1735[98[3[0[3 "Di~uoroamino#~uorodiazirine 1745[98[3[0[4 Fluorine!containin` diaziridines 174

5[98[3[1 One Haloèn\ One Nitroèn\ and Two Phosphorus Functions 1745[98[3[2 One Haloèn and Three Phosphorus Functions 175

5[98[4 ONE HALOGEN AND TWO GROUP 04 ELEMENTS 175

5[98[4[0 Metal Halodinitromethides 1755[98[4[1 Metal Bis"phosphonyl#halomethides 176

5[98[5 ONE HALOGEN AND ONE GROUP 04 ELEMENT 177

5[98[6 ONE HALOGEN AND METALLOID FUNCTION "THREE\ TWO OR ONE\TOGETHER WITH METALS# 178

5[98[6[0 One Haloèn and Three Metalloid Functions 1785[98[6[0[0 Three silicon functions 1785[98[6[0[1 Two silicon and a èrmanium function 1815[98[6[0[2 Two silicon and a boron function 1815[98[6[0[3 Three boron functions or two boron and a metal function 181

160

161 One Halo`en and Three Other Heteroatoms

5[98[6[1 One Halo`en\ Two Metalloid\ and One Metal Function 182

5[98[7 ACKNOWLEDGEMENTS 182

5[98[0 ONE HALOGEN AND THREE CHALCOGENS

5[98[0[0 One Halogen and Three Oxygen Functions

Acyclic covalent halogenides having the general structure*one halogen and three oxygen func!tions*are known for chlorine and ~uorine[ In most cases\ the oxygen substituents are poly!~uorinated or polynitrated groups[

Poly"nitro#alkyl chloro ortho!formates are reactive intermediates in the synthesis of explosiveortho!carbonates and are themselves explosive compounds ð72USP356604Ł[ They have been preparedby chlorination of the corresponding trichloromethyl disul_des "Scheme 0#^ their reaction with theHFÐpyridine complex yields ~uoro ortho!formates ð72JEM84Ł through a chlorineÐ~uorine exchangereaction[ Highly ~uorinated peroxide derivatives*exhibiting a better thermal stability than non!~uorinated analogues*are prepared by CsF!catalyzed ~uorination of the corresponding carbonylcompounds "Equation "0## ð57JOC1984\ 65JFC"6#490Ł[ In both cases\ limitation of sample size andsuitable safety equipment are required[

R

O

O

R

SOR

S

Cl

Cl

Cl

R

O

O

R

ClORCl

Cl

+ Cl2 + SCl2 + ClSCCl360 °C95%

R = C(NO2)2F

Scheme 1

R

O

O

R

ClOR

R

O

O

R

FOR+ HF/pyridine25 °C79%

O

O

ORO

RO

F

O

O

FO

RO

RO

(1)CsF

–78 °C

R = CF3, 100%SF5, 60%

+ F2

Reaction of carbon tetrachloride with penta~uorophenol in the presence of aluminum chloride\or with bromine ~uorosulfate\ gives the trisubstituted species in low yields and as a mixture withseveral by!products "Scheme 1# ð57IC323\ 77ZOR0402Ł[

50%

16%

Cl

F5C6O

F5C6O

F5C6O

25%

+ (F5C6O)4C

22 °CCl

FSO2O

FSO2O

FSO2O

FSO2O

FSO2O

+ ...

+ + BrClCCl4 + FSO2OBr

AlCl3

80 °C

27%

CCl4 + F5C6OH

Cl

Cl

Scheme 2

162Three Chalcoèns

5[98[0[1 One Halogen\ Sulfur\ and Oxygen Function

5[98[0[1[0 One halogen and three sulfur functions

"i# Acyclic covalent haloènides

Compounds of this type have been reported with sul_de\ oligosul_de\ and sulfone substructures[Polyhalogenated derivatives are by far the most numerous[ The principal methods of preparationare exempli_ed below[

"a# From thiocarbonyl compounds and haloèns[ The oldest method of preparation was describedby Hass and Klug ð55AG"E#734\ 57CB1598Ł[ This involves the rapid and quantitative addition ofchlorine "or bromine# to bis"tri~uoromethyl# trithiocarbonate to give the sulfenyl chloride "Equation"1##[ Several examples of halogenations using chlorine and thionyl chloride have been describedsubsequently "Equation "2# and Table 0#[ Starting materials are either trithiocarbonates with strongelectron withdrawing groups\ R0 and R1\ or sulfone derivatives[ Under similar conditions\ bromineand iodine failed to react with trithiocarbonate!S\S!dioxides "entries 1 and 2 in Table 0#[

Cl

F3CS

ClS

F3CS Br

F3CS

BrS

F3CSS

F3CS

F3CS

+ Cl2 (or Br2) (or )–78 °C, 1h

90% 60%

(2)

X

R2S

XS

R1SS

R2S

R1S "X2"(3)

Table 0 Halogenation of thiocarbonyl compounds[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐEntry R0 R1 Reaènts and conditions Yield ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ0 CF2 CF2 FCl\ −79>C "mixture# 65CB08651 PhS PhSO1 Cl1\ CCl3 79 65CB09582 PhS 3!Me[C5H3SO1 Cl1\ CCl3 77 65CB09583 CN CN Cl1\ −09>C\ CH1Cl1 79 70CB00214 Cl2CS Cl2CS Cl1\ CCl3 80 73SUL745 Cl2CCCl1S Cl2CCCl1S Cl1\ CCl3 099 74T40346 PhCH1 Cl2CS SO1Cl1\ CH1Cl1 87 74T40347 Me Me SO1Cl1\ −04>C\ pentane 42 73SUL130*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Chlorination with chlorine or thionyl chloride is a very e.cient approach to sulfenyl chlorides]most of the reactions reported in Table 0 are rapid\ clean\ and quantitative[ The sulfenyl chloridesthus obtained are useful starting materials for the synthesis of more elaborate\ trisubstituted trithioortho!formates[ The most signi_cant examples of nucleophilic substitution reactions of the SClfunction by amines\ thiols\ and amides "Equation "3## are given in Table 1[ The reactivity of theS0Cl bond is generally increased by electron withdrawing substituents R0 and R1[ Some of thepoly~uoro derivatives are claimed to be fungicidal agents\ and the synthesis of the phthalimidoderivative "entry 1 in Table 1# has been patented ð69GEP0897579Ł[

X

R2S

XS

R1S X

R2S

NuS

R1SNu–

X = Cl or F(4)

"b# From thiocarbonyl compounds and sulfenyl haloènides[ Thiocarbonates having the generalstructure ðR"S#nSŁ1C1S "n�0\ 1 and 2# are formed from thallium or barium thiocarbonates byreaction with sulfenyl chlorides "Equation "4# and Table 2#[ When an excess of sulfenyl chloride isused\ the transient thiocarbonate reacts further to give the chlorothio ortho!formate in fair tomoderate yields "entries 0 and 1 in Table 2#[ The synthesis of various polyhalogenated ortho!formates bearing disul_de or trisul_de units has also been reported ð74T4034Ł[


Table 1 Nucleophilic substitution reactions of sulfenyl chlorides[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR0 R1 Nu Conditions Yield ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐCF2 CF2 Et1NH petroleum 71 65CB0865CF2 CF2 phthalimide C5H5\ Et2N 43 69GEP0897579\ 65CB0865CF2 CF2 K!pyrrole pentane 55 72CB2214Cl2CS Cl2CS Na phthalimide CH1Cl1\ H1O 49 74T4034CF2 CF2 NH2 −79>C 56 63CZ098PhS 3!Me[C5H3SO1 morpholine CHCl2 89 65CB0958PhS Ph!SO1 morpholine CHCl2 76 65CB0958PhS 3!Me[C5H3SO1 PhSH CHCl2 64 65CB0958PhS 3!Me[C5H3SO1 ButSH CHCl2 76 65CB0958PhS 3!Me[C5H3SO1 3!Me[C5H3SO1Na C5H5 17 65CB0958PhS 3!Me[C5H3SO1 MeCOSH CCl3\ 49>C 84 75T628CF2 CF2 AgCN 19>C 86 65CB0865CF2 CF2 AgOCN 49>C 5 65CB0865CF2 CF2 AgSCN 19>C 55 65CB0865CF2 CF2 AgSeCN 19>C 68 65CB0865CN CN H3NSCN SO1\ −19>C 81 70CB0021CF2 CF2 F1C�S hn 29 65CB0865*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

X

R1S

R2SS

R1SS

R1S

R1SR2SX

(5)

Table 2 Addition of sulfenyl chlorides to thiocarbonyl compounds[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR0 R1 Rea`ents and conditions Yield ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐCF2S CF2 Tl1CS2¦F2CSCl 24 65CB2321Cl2CS1 Cl2CS BaCS2¦Cl2C!S1Cl\ MeCN 09 74T4034Cl2CS Cl2C Cl2CSCl\ MeCN\ 79>C 74T4034Cl2CCl1CS Cl2CCl1C Cl2C!Cl1CSCl\ MeCN\ 79>C 45 74T4034FCl1CCl1CS FCl1CCl1C FCl1C!Cl1C!SCl\ MeCN\ 79>C 74T4034Cl2CS Cl SCl1\ 9>C 099 73SUL74CF2 CF2 F2CSF\ −085 to −59>C 40 81ZN"B#258*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Sulfur dichloride reacts cleanly at low temperature with bis"trichloromethylthio# trithiocarbonateto give the corresponding chlorothio ortho!formate in quantitative yield "entry 5 in Table 2#[The reaction of bis"tri~uoromethyl# thiocarbonate with tri~uoromethylsulfenyl ~uoride must beperformed at very low temperature "−089>C#\ because of the much higher reactivity of F2CSFcompared to F2CSCl[ The structures of tris"trichloromethyldithio#! and "trichloro!methyltrithio#chloro ortho!formate "entries 1 and 2 in Table 2# have been established by x!raycrystallography[

"c# By halo`enation of trisulfonylmethanes[ Trialkyl!\ triaryl!\ and tri~uoro!sulfonylmethanes arevery strong acids^ in the presence of bases "Ag1CO2 or NaOH# the corresponding silver or sodiumsalts are formed[ They react smoothly with halogens "Cl1\ Br1\ and I1# "Equation "5# and Table 3#[The iodo derivatives are generally less stable than their chloro or bromo analogs[ The ~uoroderivative could not to be isolated from the reaction of "F2CSO1#2C−Ag¦ with XeF1 ð77IC1024Ł\ but"FSO1#2CF is obtained from reaction of "FSO1#2CH with XeF1 ð79AG"E#831Ł[ A few examples ofdirect halogenation of trisulfonylmethanes in re~uxing CCl3 in the absence of any deprotonatingagents have been reported "entries 7Ð05 in Table 3#[ Yields are satisfactory[

SO2R2

R1SO2

R1SO2

X

R2SO2

R1SO2

R1SO2

X2/Ag2CO3

or X2

(6)

Only two examples of lithiated chlorobis"sulfonyl#methanes have been reported[ They react with

164Three Chalcoèns

Table 3 Halogenation of trisulfonylmethanes[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR0 R1 Reaènts and conditions Yield ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐMe Me Cl1\ NaOH\ H1O 77 35RTC42Me Me Br1\ NaOH\ H1O 84 35RTC42F F Br1\ Ag1CO2 85 79AG"E#831\ 72ZOR68F F l1\ Ag1CO2 85 79AG"E#831\ 72ZOR68F F XeF1\ −09>C\ CF1Cl1 79AG"E#831CF2 CF2 Cl1\ Ag1CO2\ 9>C\ CH1Cl1 89 77IC1024CF2 CF2 Br1\ Ag1CO2\ 9>C\ CH1Cl1 83 77IC1024Et Me Cl1\ 69>C\ CCl3ÐCHCl2 54 65ZOR447Et Me Br1\ 69>C\ CCl3ÐCHCl2 81 65ZOR447Ph Me Cl1\ 69>C\ CCl3ÐCHCl2 64 65ZOR447Ph Me Br1\ 69>C\ CCl3ÐCHCl2 84 65ZOR4473!Me[C5H3 Me Cl1\ 69>C\ CCl3ÐCHCl2 69 65ZOR4473!Me[C5H3 Me Br1\ 69>C\ CCl3ÐCHCl2 79 65ZOR4473!Cl[C5H3 Me Cl1\ 69>C\ CCl3ÐCHCl2 59 65ZOR4473!Cl[C5H3 Me Br1\ 69>C\ CCl3ÐCHCl2 89 65ZOR4473!Me!2!NO1[C5H2 Me Br1\ 69>C\ CCl3 52 65ZOR1472*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

phenylsulfenyl chloride at room temperature to a}ord chloro"phenylthio#bis"sulfonyl#methanes inlow to moderate yield "Equation "6## ð61LA"647#021Ł[

R = Et, 17% Ph, 61%

Cl

RSO2

PhS

RSO2Cl

RSO2

RSO2 i, BunLi ii, PhSCl

RT(7)

"ii# Cyclic covalent haloènides

"a# From thiocarbonyl compounds and haloèns or sulfenyl halides[ The previously describedaddition of halogens or sulfenyl halides to trithiocarbonates has been applied e.ciently to thesynthesis of cyclic derivatives "Scheme 2# ð76SUL48\ 80CB1914Ł[ The four!membered cyclic thio!carbonyl compounds react considerably faster than their acyclic analogues[ This re~ects the dimin!ished ring strain upon sp1Ðsp2 rehybridization of the C!1 center in the dithietane[

SS

S

F3C

F3C

S

S

F3C

F3CCl

SCl+ Cl2

CH2Cl2

0 °C100%

S

SS

S

S

Cl

SSRCl

ClRSCl

Cl

Cl+

25 °C

Scheme 3

R = CCl3, 86%C2Cl5, 75%SCCl3, 58%SC2Cl5, 68%

"b# Fluorination of trithiosubstituted carbocations[ Exchange of the AsF5− counterion with a~uoride anion in cationic 0\2!dithietane derivatives gives rise to a stable ~uorinated compound whenR�CF2\ or to an unstable one when R�Me "Equation "7## ð89CB0524Ł[ Previously\ the sameapproach had been applied to the synthesis of symmetrical dithietanes from trithiomethyl car!bocations "Scheme 3# ð76CB318Ł[ The _rst step of the reaction is the dimerization of a ~uoro!dithioformate\ induced by the strong acidic medium[ Formation of the covalent C0F bond is thenpromoted by addition of ether\ as a solvent\ to the reaction mixture[


S

SSR

S

S

F

SR

R = CF3, 98%Me, unstable

NaF

AsF6–

SO2

25 °C+ NaAsF6+

F

F

F

F(8)+

S

SSCF3

S

S

F

SCF3F3CS

F

F3CS

FS

F

F3CS F–

ether48%

SbF5, HF

–30 °C2

SbF6–

+

Scheme 4

5[98[0[1[1 One halogen\ two sulfur\ and one oxygen function

Only two examples of this class of compounds have been isolated and identi_ed] both arederived from carbohydrates and both are symmetrical disul_des resulting from chlorine addition todithiocarbonates "Equation "8## ð58JOC0531Ł[ The _nal products precipitate from the solution aswhite solids[ They are used as intermediates in the synthesis of sugar chlorothioformatesð60CAR"05#034Ł[

S

RO

S

S

S

OR

S

RO

S

S

S

OR

S

Cl

ClS

S

SCl

Cl

ORROether

+ Cl2

=

(9)

bis (1,2:5,6-di-O-isopropylidine-3-O-thiocarbonyl-α-D-glucofuranose) disulfide, 100%

bis (methyl 4,6-O-benzylidine-2-(and 3-) O-thio-carbonyl-α-D-glucopyranoside) disulfide, 35%

Work done in the early 0879s has shown that O\S!dimethyl dithiocarbonate reacts at 9>C withsulfuryl chloride to give the expected chlorinated adduct which undergoes a rapid intramolecularrearrangement to a}ord a methoxydichloro"methyldithio# derivative "Scheme 4# ð72TL4572Ł[ In thelight of this result\ a reinterpretation of the earlier literature data on chlorination of thioesters seemsto be necessary[

Cl

MeS

ClS

MeOS

MeS

MeOCl

MeSS

Cl

MeO+ SO2Cl2

Scheme 5

5[98[0[2 One Halogen\ Selenium\ and Sulfur Function

The methods available for the synthesis of haloselenothio ortho!formates are analogous to thoseused for the corresponding trithio ortho!formates\ but with fewer examples[ When sulfur andselenium substituents are perhalomethyl\ CFnCl"2−n#\ chloro ortho!formates have been isolated"Equation "09##^ the only bromo derivative cited ð75ZN"B#302Ł seems to be unstable[ "CF2Se#1C1Sreacts with chlorine at low temperature by addition of halogen to the thiocarbonyl group "Equation"00## ð63CZ400Ł[ No experimental details have been given[ A report from the mid 0879s concernsthe addition of sulfuryl "or selenyl# chlorides to thiocarbonyl derivatives under UV irradiation[Physical and spectroscopical data of the new substances are provided[ "Table 4# ð75ZN"B#302Ł[

Cl

F3CSe

ClS

F3CSeS

F3CSe

F3CSe

+ Cl2–80 °C

(10)

166Two Chalco`ens

Cl

F3CY

RS

F3CSeS

F3CY

F3CSeRCl

(11)

Table 4 Addition of sulfuryl and selenyl chlorides to thio!carbonyl derivatives[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐEntry Y Rea`ents and conditions Yield ")#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ0 Se F2CSCl\ hn 771 Se F2CSeCl\ hn 742 Se F1ClCSCl\ hn 403 Se FCl1CSCl\ hn 274 S F2CSeCl\ hn 765 S F2CSCl\ hn 67*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

5[98[1 ONE HALOGEN AND TWO CHALCOGENS

5[98[1[0 One Halogen\ Two Chalcogens\ and a Nitrogen Function

As far as covalent halides are concerned\ a few examples of this type have been described\ witheither oxygen or sulfur as the chalcogens[ A unique compound containing two oxygen and anitrogen functions was obtained by reaction of peroxydisulfuryl di~uoride with ClCN under thermalconditions "Equation "01## ð64IC481Ł[ The suggested mechanism involves formation of a nitrene andthe reaction pathway shown in Scheme 5 is proposed to account for the addition of the FSO1O =radical to the unsaturated carbonÐnitrogen system[ This radical addition to ClCN occurs quan!titatively and is su.ciently facile to be synthetically useful[

Cl

FSO2O

(FSO2O)2N

FSO2OCICN + (FSO2O)2

80 °C, 12 h

82%(12)

N:Cl

FSO2O

FSO2ON

Cl

FSO2O

ClCN FSO2O• FSO2O•

•

Cl

FSO2O

(FSO2O)2N

FSO2ON:Cl

FSO2O

FSO2O + (FSO2O)2

Scheme 6

Bis"2!nitroarylsulfonyl#bromonitromethanes are obtained from bis"arylsulfonyl#"methylsulfonyl#methanes "Scheme 6#[ After polynitration with HNO2ÐH1SO3 the methylsulfonyl group is easilyremoved in basic medium[ Two bromination methods\ direct bromination with potassium hypo!bromite and basic cleavage followed by bromine addition\ were outlined ð65ZOR1472Ł[

Arylazo derivatives of bis"arylsulfonyl#chloromethanes are yellow crystalline compounds whichare readily soluble in most organic solvents[ They are prepared from bis"arylsulfonyl#chloro!methanes in basic medium by reaction with aryldiazonium chlorides "Equation "02## ð57ZOR213Ł[

Cl

4-RC6H4SO2

4-RC6H4SO2

Cl

4-RC6H4SO2

N

4-RC6H4SO2

ArN

+ ArN2+Cl–

NaOH

RT, 30min80–94%

R = H, Me, Cl, NO2Ar = C6H5, 4-Me-C6H4, 4-Cl-C6H4, 4-O2N-C6H4, 4-MeO-C6H4, 4-HO2C-C6H4, 2-MeO, 5-Cl-C6H3, 2-Me, 5-Cl-C6H3

(13)


SO2Me

4-RC6H4SO2

4-RC6H4SO2

SO2Me

ArSO2

O2N

ArSO2

ArSO2

ArSO2

Br

ArSO2

O2N

ArSO2

HNO3/H2SO4

RT, 3hR = H, 75%

Me, 73%Cl, 80%

R = Me, 90%Cl, 85%

Br2,CCl4

70 °C, 4h

R = H, 80%Me, 95%Cl, 85%

ArSO2 = 4-R, 3-O2N-C6H3

NaHCO3 KOBr

Scheme 7

NO2

5[98[1[1 One Halogen\ Two Sulfur\ and a Phosphorus Function

Triethoxyphosphonium bis"phenylsulfonyl#methylide is one of the few known stabletrialkoxyphosphonium ylides\ most of which are only reaction intermediates[ It reacts as a veryweak nucleophile^ for example\ with bromine it gives the 0!bromomethylphosphonate in very goodyield "Scheme 7# ð77S802Ł[

IPh

PhSO2

PhSO2

Br

PhSO2

(EtO)2P(O)

PhSO2P(OEt)3

PhSO2

PhSO2

(EtO)3P+Cu(acac)3, CHCl3

80 °C, 7.5 h

87% 98%

Br2, CCl4

RT, 1h

Scheme 8

Mixed sulfonicÐphosphonic acids have been synthesized for evaluation as potential electrolytesin fuel cells[ The starting material "EtO#1P"O#CFBr1 was converted into its disodium 0!~uoro!0\0!disulfonylmethylphosphonate salt by repeated reaction with sodium dithionite and hydrogenperoxide "Scheme 8# ð78CJC0684Ł[ Yields were satisfactory[

F

Br

(EtO)2P(O)

NaSO3 F

NaSO2

(EtO)2P(O)

NaSO3 F

NaSO3

(EtO)2P(O)

NaSO3

F

Br

(EtO)2P(O)

Br F

Br

(EtO)2P(O)

NaSO2 F

Br

(EtO)2P(O)

NaSO3

H2O2

–15 °C, 1 h80%

H2O2

0 °C, 5 h

Na2S2O4, MeCN/H2O

RT, 4 h

NaS2O4

0 °C, 4 h32%

75%64%

Scheme 9

5[98[1[2 One Halogen\ Two Sulfur\ and a Metal Function

All the known compounds bearing one halogen\ two sulfur\ and one metal function on the samecarbon atom have the general structure "0#[

X = Cl,BrM = Li,Na,K,AgR = Ph,CF3

X M+

RSO2

RSO2

(1)

–

It has been found that the action of strong bases "for R�Ph# or even weak bases "for R�CF2#leads to metallation at the C0H bond of bis"sulfonyl#halomethanes "Equation "03## ð61LA"647#021\62JOC2247\ 66ZOR164Ł[

168One Chalco`en

X + MY

RSO2

RSO2

X M+

RSO2

RSO2

+ YH–

X = Cl, Br Cl, Br Cl, Br

R = Ph CF3 Ph, Me, Et

MY = BunLi, MeONa / MeOH, KOH / H2O K2CO3 / MeOH, Na2CO3 / MeOH, Ag2CO3 / MeOH MeONa / MeOH, BunLi

(14)

pKa values for some monohalodisulfonylmethanes "R�Ph\ Me\ Et# have been established bypotentiometric titration in waterÐdioxane "0 ] 0# ð61LA"647#021Ł[ The metallohalomethanes are crys!talline substances\ soluble in water\ but insoluble in nonpolar or low polarity organic solvents[ Theyare very stable under ordinary conditions and have been found to be stable up to 149>C in somecases[

5[98[2 ONE HALOGEN AND ONE CHALCOGEN

5[98[2[0 One Halogen\ One Chalcogen\ and Two Group 04 Elements

5[98[2[0[0 One halogen\ one oxygen\ and two nitrogen functions

"i# From per~uoroimines

Addition of alcohols to N!~uoroimines gives adducts the stability which depends on the electronwithdrawing character of the carbon substituents[ If these substituents are F and NF1 or F and CF2\the adduct decomposes spontaneously with HF elimination to yield mainly a new ~uoroimine"Scheme 09#[ If both carbon substituents are NF1 groups\ stable adducts are obtained[ Interactionof these stable liquid compounds with NOF or NO1Cl causes replacement of the NHF group by F\through an unstable intermediate bearing an N"F#NO substituent "Equation "04##[ The compoundsdescribed here are patented as good oxidants ð61USP2696444Ł and are shatteringly explosive undercertain conditions[ Suitable protective equipment should be used during all phases of workð62JOC0954Ł[

NF

F2N

F

F

FHN

MeO

F2N NF

F2N

MeO

+ ...MeOH –HF

Scheme 10

NF2

FHN

MeO

F2N F

F2N

MeO

F2N + NNO (or NNO2)+ NOF–HF

(–HCl)

(or NO2Cl)

(15)

Oxidation of per~uoroimines by aromatic peroxyacids or H1O1 a}ords oxaziridines "1#ð78USP3763764\ 81EUP385302Ł[

N

O

RF

R1R2N

(2)

"ii# From ~uorotrinitromethane

In marked contrast to chloro! and bromotrinitromethane\ whose reactions with bases and reduc!ing reagents generally lead to nitroform anions\ ~uorotrinitromethane reacts with certain nucleo!philes with formal substitution of a nitro group "Equation "05## ð57JOC2962Ł[


F

O2N

O2N

O2N F

O2N

RO

O2N + NaNO2+ RONa/ROH

R = Et, 74%CF3CH2, 55%

(16)

"iii# Diazirines from amidinium salts or ~uoroimines

In 0854\ Graham reported the direct preparation of 2 aryloxy!2!halodiazirines by the action ofaqueous NaOCl "or NaOBr# on various isoureas "Equation "06# and Table 5# ð54JA3285Ł[ Despitethe importance of this interconversion\ the mechanism remains only partly elucidated[ The originalsuggestions are summarized in Scheme 00[ Not all of these intermediates have been isolated andcharacterized ð70JOC4937Ł[

NH

R2HN

R1O

N

N

X

OR1NaOX

(17)

Table 5 Preparation of 2!halo!\ 2!alkoxy!\ or aryloxy!diazirines[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR0 R1 X Rea`ents and conditions Yield ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐMe H Cl NaOCl\ NaCl\ LiCl\ 14>C\ DMSO 59 54JA3285Me H Cl NaOCl\ NaCl\ 14>C\ DMSO 53 68JCS"P1#0187Bui H Cl NaOCl\ NaCl\ 14>C\ DMSO 47 68JCS"P1#0187Ph PhSO2 Cl NaOCl\ LiCl\ −4>C\ DMSOÐpentane 26 71JOC3066CD2 H Cl NaOCl\ NaCl\ LiCl\ 14>C\ DMSO 75JA88Me07O H Cl NaOCl\ NaCl\ LiCl\ 14>C\ DMSO 75JA88PhCH1 H Cl NaOCl\ NaCl\ LiCl\ 14>C\ DMSO 46 76TL0858PhCH1 H Br NaOBr\ 9>C\ DMSOÐpentane 24 89JPO583PhCHD H Cl NaOCl\ 04>C\ DMSOÐpentane 89TL3604c!C2H4CH1 H Cl NaOCl\ LiCl\ 4>C\ DMSOÐpentane 78TL1362EtCHMe H Cl NaOCl\ LiCl\ 09>C\ DMSOÐpentane 81JA8275*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

NH

H2N

RO

NX

H2N

RO

NX

XHN

RONaOX NaOX

NX

XN

RON:

XN

RON

N X

OROH– –X–

Scheme 11

–

Diazirines have been widely investigated as sources of numerous halocarbenes[ Successiveimprovement of the synthetic approach\ by using N!substituted isoureas as starting materials\greatly enlarged the scope and potential of diazirine chemistry[ As neat liquids\ the diazirines areunpredictably explosive at ambient temperatures\ but in solution they can be handled safely[ Chloro!or bromoalkoxydiazirines are converted into the corresponding ~uoroalkoxydiazirines simply uponstirring with anhydrous tetra!n!butylammonium ~uoride "tbaf# in acetonitrile "Equation "07##ð72JA5402\ 75JOC1057\ 75TL308\ 89JPO583Ł[

N

N F

ORN

N X

OR Bun4NF, MeCN

0–25 °C, 2–6 h

R = Cl, 55%Cl, 39%Br, -Cl, 40%

X = PhPhMeCH2Ph

(18)

170One Chalco`en

The reductive de~uorinationÐcyclization of methoxytri~uoroformamidine in the presence offerrocene at room temperature represents an alternative approach to 2!~uoromethoxydiazirine"Equation "08## ð62JOC0954Ł[

N

N F

OMeNF

F2N

MeO Ferrocene

30%(19)

5[98[2[0[1 One halogen\ one sulfur\ and two nitrogen functions

0!Chloro!0\0!dinitromethyl sul_des or sulfones are the only reported representatives of this classof compounds[ They are usually obtained by treatment of the potassium salts of dinitromethylsul_des or sulfones with chlorine "Equation "19## ð62IZV249\ 64IZV1649Ł[ The nucleophilicity of thepotassium salts is so weak that they do not react even with iodomethane[ An alternative route tothe analogous sul_de derivatives "Scheme 01# involves the addition of PhSCl to iodonium nitroylides\which proceeds by cleavage of the intermediate iodonium salt ð67IZV1237Ł[ The iodonium nitroylideis a thermally unstable crystalline compound which decomposes rapidly in solvents like acetone\ethanol\ and dichloromethane and explosively after isolation in air or under an inert gas[ Substituentssuch as NO1 on the benzene ring increase the stability of these dinitroylides[

R K+

O2N

O2N

Cl

O2N

R

O2NCl2

ether or CH2Cl2

R = MeSO2, 92%2,4-(O2N)2-C6H3SO2, 30%MeS, 90%2,4-(O2N)2-C6H3, 65%

– (20)

IPh

O2N

O2NIPh

O2N

PhS

O2N Cl

O2N

PhS

O2N + (PhS)2C(NO2)2

+

Cl–

45%

excess PhSCl

Scheme 12

5[98[2[0[2 One halogen\ one chalcogen\ and two phosphorus functions

The _rst approach to this kind of compound is a traditional MichaelisÐArbuzov reaction betweentriethyl phosphite and trichloromethyl phenyl ether "Scheme 02# ð69JPR364Ł[ Analogous tetraethylhalomethoxymethylene bisphosphonates are obtained by radical halogenation of the correspondingmethoxymethylene bisphosphonates "Equation "10## ð73ZOB1493Ł[

Cl

PhO

(EtO)2P(O)

(EtO)2P(O)(EtO)3P

160 °C64%

(EtO)3P + PhOCCl3120 °C

(EtO)2P(O)CCl2OPh

Scheme 13

OMe

(EtO)2P(O)

(EtO)2P(O)

Br

MeO

(EtO)2P(O)

(EtO)2P(O)NBS, benzene

AIBN, 80 °C, 2-5 h, 52%(21)

Unexpectedly\ two products were obtained during the reaction of the methylene bisphosphonatesalts\ ð""RO#1PO#1CHŁ−M¦ "M�Li\ Na\ K#\ with CF2SCl[ The expected sulfenyl derivative isobtained in a mixture with chloro"tri~uoromethylthio#methylene bisphosphonate\ which resultsfrom a chlorination process "Equation "11##[ The use of aluminum trichloride reduces the proportion


of chlorinated by!product "05)# with respect to the sulfonylated product "63)# ð74JCS"P0#0824Ł[CClF1SCl and CCl1FSCl have also been used in analogous reactions[

SCF3

(PriO)2P(O)

(PriO)2P(O)

Cl

F3CS

(PriO)2P(O)

(PriO)2P(O)

i, BunLi ii, CF3SCl

ether

43% 14%

(PriO)2P(O)

(PriO)2P(O)

+ (22)

(PriO)2P(O)

(PriO)2P(O)

43%

+

5[98[2[1 One Halogen\ One Sulfur\ and Two Silicon Functions

Only one member of this family has been reported in the literature of the late 0879s onwards[ It wasprepared by NBS bromination of bis"trimethylsilyl#methyl "trimethylsilyl#methyl sul_de "Scheme 03#ð76CPB0623Ł[ This compound is used as a precursor for the generation of a thiocarbonyl ylide\ whose0\2 cycloaddition to several dipolarophiles leads to tetrahydrothiophene derivatives[

TMS ClNa2S•5H2O

Bu4N+Br–, H2O, 100 °C, 5h

86%

S

TMS

TMS

i, BusLi, ii, TMS-Cl

THF, TMEDA, 0 °C 72%

Scheme 14

S

TMS

TMS

Br

TMS

S

TMS

NBS, CCl4

RT. 100%

TMSTMS

5[98[3 ONE HALOGEN AND THREE GROUP 04 ELEMENTS

5[98[3[0 One Halogen and Three Nitrogen Functions

5[98[3[0[0 Halotrinitromethanes

Halotrinitromethanes have been extensively studied in view of their use as oxidants in mono!propellant fuels and in bipropellant systems with hypergolic fuels ð57USP2308514Ł[ The best methodsfor the preparation of halotrinitromethanes are electrophilic halogenations of trinitromethane salts"Equation "12##[ A wide range of halogenating agents has been tested in various reaction conditions^the most successful syntheses are collected in Table 6[ In entry 0\ the reaction conditions have beenoptimized] aprotic solvents and room temperature "19>C# are essential factors[ Direct ~uorinationof trinitromethane with ~uorine in water "89) yield# or methanol "69) yield# was also reportedð57IZV545\ 57IZV565Ł as a satisfactory synthetic method[

O2N

O2N

X

O2N

O2N

O2NNO2 M+ + M+Y–X-Y

(23)–

Table 6 Electrophilic halogenation of nitroform salts[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐM XY Conditions X Yield ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐK FClO2 THF\ 14>C\ 00 h F 61 60IZV0376K F1Xe MeCN\ 19>C F 67 76ZOR0546Na F1:N1 H1O\ 9>C\ 0[4 h F 81 57JOC2979NH3 F1:N1 H1O\ 9>C F 69 57IZV545Na NCS H1O\ 9>C\ 19 min Cl 88 58IZV1506K ClSO2F Cl1FC!CClF1\ −29Ð9>C Cl 71 65IZV378Na NBS H1O\ 9>C\ 19 min Br 87 58IZV1506K ICl CCl3\ 09>C\ 29 min l 60 66IZV1947*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

172Three Group 04

When tetranitromethane reacts with anhydrous metal halides in aprotic dipolar solvents one of thenitro groups is replaced by a halogen "Equation "13## ð57USP2308514\ 58ZOR0206\ 69IZV1442\ 60IZV0962\61IZV0610\ 67USP3019893Ł[

X

O2N

O2N

O2NNO2

O2N

O2N

O2NDMF (or MeCN)

++ MX MNO2

MX = KF, RbF, 58%CsF, 49%KF/OC(CF3)2, 90%LiCl, KCl, RbCl, CsCl, 40–60%LiBr, KBr, 23–30%Na(Cl)NSO2Ph, 49%

(24)

Halotrinitromethanes have also been obtained from arylthio!\ arylseleno!\ and arylantimono!trinitromethanes by cleavage of the carbonÐheteroatom bond\ through treatment with halogens\ orwith sulfuryl chloride under mild conditions "Equation "14## ð63IZV0249\ 71IZV050\ 74IZV328Ł[ Treat!ment of arylthio! or arylseleno!trinitromethanes with gaseous hydrogen halides "HCl\ HF# in thepresence of Lewis acids or mineral acids a}ords the corresponding halotrinitromethanes "Equation"15##[ The addition of a Lewis acid promotes the nucleophilic substitution of the chalcogenidegroup\ but yields remain unsatisfactory "0Ð29)# ð78IZV1095Ł[

X

O2N

O2N

O2NYR

O2N

O2N

O2NX2

+ RYX

Y = S

SbSe

X2 = Cl2SO2Cl2Br2Cl2Cl2Br2

R = Ph2,4-(O2N)2-C6H32,4-(O2N)2-C6H3PhPhPh

DME, 0 °C, 2 hMeCN, 20 °C, 5 minMeCN, 20 °C, 5 minCH2Cl2, 20 °C, 3 hCH2Cl2, 20 °C, 1hCH2Cl2, 20 °C, 1h

86%80%78%52%79%75%

(25)

X

O2N

O2N

O2NYR

O2N

O2N

O2N + RYH+ HXLewis acid

20 °C, 1h

Y = S, Se X = F, Cl Lewis acid = AlCl3, SbCl5Solvent = CH2Cl2, MeCN, DMSO

(26)

Trinitromethyl sulfones were also tested as starting materials for the synthesis of halo!trinitromethanes "Equation "16##[ The C0SO1 bond was cleaved e.ciently by halogenated electro!philes "X1\ BrONO1\ HCl# ð66IZV264Ł[

X

O2N

O2N

O2NSO2Ph

O2N

O2N

O2NMeCN

20 °C, 0.5–2.4 h

RSO2X+ X2 +

X2 = Cl2, 80% Br2, 80%

(27)

Electrophiles "X1�Cl1\ Br1\ SO1Cl1\ NCS or NBS# very readily cleave the S0C bond of dimethyl!"trinitromethyl#sulfonium tetra~uoroborate to give the corresponding halotrinitromethanes in fairto good yields "59Ð79)# "Equation "17## ð66IZV1429Ł[ The starting material\ obtained by nitrationof dimethylsulfonium dinitromethylide with nitronium tetra~uoroborate\ is stable for at least 13 hat 19>C[ It also reacts under mild conditions with nucleophiles "HCl\ HBr# to give the expectedhalotrinitromethanes[ In this case\ yields are low "05Ð22)# because of competing reactions betweenthe product halotrinitromethanes and dimethyl sul_de[

X

O2N

O2N

O2NSMe2

O2N

O2N

O2NMeCN

–20 °C, 20 min

+XSMe2 BF4

+ X2 ++

BF4–

– (28)


All the approaches described above employ the halogenation of preformed trinitromethyl moi!eties[ There is only one report of the nitration of a halodinitromethane[ Nitryl ~uoride was employedas the nitrating agent "Equation "18##[ The reaction did not require prior salt formation\ but the useof ammonium salts of halodinitromethane slightly increases the yield "to 44)# ð63IZV804Ł[

X

O2N

O2N

O2NX

O2N

O2NMeCN

–15 °C

+ FNO2

X = F, 47% Br, 39%

(29)

5[98[3[0[1 Miscellaneous halonitromethanes

Bromo! and chlorodinitromethanes react with a\a?!dicarbonylazo compounds to give N!"halodinitromethyl#hydrazine derivatives "Equation "29## ð64IZV1727Ł[ "Arylazoxy#dinitromethanes\bearing an acidic proton\ undergo facile bromination in basic medium to give the "aryloxy#bromo!dinitromethanes "Equation "20## ð81MC41Ł[ Finally\ bis"di~uoroamino#~uoronitromethaneð"F1N#1"NO1#CFŁ has been identi_ed as a colorless gas ð57USP2276922Ł[

ClClBrBr

X =

N

X

O2N

O2NX

O2N

O2NROC

NN

COR+

HN

COR

COR

R =

(30)

OMe, 81%NHMe, 67%OEt, 98%NH2, 87%

(31)N

Br

O2N

O2NN

O2N

O2NKOH

+ Br2

O–

NAr

O–

NAr

Ar = 2,4-(O2N)2•C6H3, 80%

++

5[98[3[0[2 Halotriaminomethanes

Several poly"~uoroamino#halomethanes "Scheme 04# have been patented as precursors for bleach!ing agents\ explosives\ rocket fuels\ and pyrotechnic agents ð56JOC2748\ 56USP2243106\ 57IC0536\58USP2349651\ 61IC307\ 61USP2578459\ 62JOC0964\ 62USP2644393Ł[ This compilation is not exhaustive[ Thevarious reported syntheses are performed on small scale and generally a}ord complex mixtures of~uorinated products\ including those having the general structure "R1N#2CF[ The reaction betweenNCl2 and CCl3 in the presence of AlCl2 gives a mixture of four compounds\ one of them being"Cl1C1N#2CCl "16)# "Scheme 05# ð61RTC220Ł[

F

F2N

F2N

F2N Br

F2N

F2N

F2N F

RFN

F2N

F2N

F

H2N

F2N

F2N F

O2N

F2N

F2N F

N

F2N

F2N(NF2)3C-N

Scheme 15

Cl

N

N

N

Cl2C

Cl2C

Cl2C

N

N

Cl2C

Cl2CCl3CNNCl3 + CCl4

AlCl3+ (ClCN)3 +

27% 35% 32% 0.7%

+

Scheme 16

Cl

Cl

Cl

Cl

174Three Group 04

5[98[3[0[3 "Di~uoroamino#~uorodiazirine

"Di~uoroamino#~uorodiazirine was prepared from tris"di~uoroamino#~uoromethane by a reductivede~uorinationÐcyclization reaction with iodide ion in acetonitrile or with ferrocene "06)# "Equation"21## ð56JOC3934\ 57JOC0736\ 61USP2526552Ł[ Extreme caution should be used when manipulatin` "di~uoro!amino#~uorodiazirine because it can explode violently and it is sensitive to phase chan`es[

F

F2N

F2N

F2NN

N F

NF2KI or ferrocene(32)

5[98[3[0[4 Fluorine!containing diaziridines

Penta~uoroguanidine undergoes rearrangement to a diaziridine in the presence of alkali metal~uorides "MF# "Equation "22##[ CF3\ SiF3\ CO1\ and other impurites were observed in the reactionmixture[ Explosions occurred when the volatile diaziridine was condensed or volatilized[ Thediaziridine is unstable at room temperature and must be stored at −67>C ð57JOC2378Ł[ A similardiaziridine was also obtained by a reductive de~uorinationÐcyclization reaction of bis"di~uoramino#ð"tri~uoromethyl#~uoraminoŁ~uoromethane "Equation "23## ð57JOC0736Ł[

NF

F2N

F2NFN

FN F

NF2

25%

MF

M = K, Rb

(33)

F

(F3C)FN

F2N FN

N F

NF2

F2N33%

ferrocene

F3C

(34)

5[98[3[1 One Halogen\ One Nitrogen\ and Two Phosphorus Functions

Compounds of this class bear\ essentially\ two phosphoryl groups and an isocyanate or ammoniumfunction on the carbon atom[

The reaction of trichloromethyl isocyanate with various amounts of triethyl phosphite was studiedunder several conditions in order to determine the number of chlorine atoms of the trichloromethylgroup which are active in the MichaelisÐArbuzov reaction[ With optimized stoichiometry of thereagents and reaction conditions\ a 22Ð31) yield of the diphosphonyl substituted derivative isobtained "Equation "24##[ In all cases side products are formed ð62ZOB433Ł[ The analogous reactionswith a dialkyl halophosphite and trichloromethyl isocyanate a}orded only the correspondingbis"phosphoryl#halomethyl isocyanate in moderate to good yields "Equation "25##[ This reactionwas extended to 1!chloro!0\2!dioxaphospholanes] as expected\ the MichaelisÐArbuzov rearrange!ment led to ring opening^ the yield is very low "5)# ð66ZOB1655Ł[

Cl

OCN

(EtO)2P(O)

(EtO)2P(O)2 (EtO)3P + Cl3CNCOtoluene

70-100 °C[(EtO)2P(O)]2O(EtO)3P(O)+ + (35)

Cl

OCN

X(EtO)P(O)

X(EtO)P(O)(EtO)2P-X + Cl3C-NCO2∆

X = Cl, 42% F, 79%

(36)

Dichloro~uoromethyl isocyanate has been used in a reaction with dialkyl chlorophosphites witha reagent ratio of 0 ] 1[ The main product was the "alkoxychlorophosphonyl#"alkoxy~uoro!phosphonyl#chloromethyl isocyanate^ it resulted from the reaction of the tautomericform\ Cl1C1NC"O#F\ of the starting isocyanate with the chlorophosphite\ followed by a second


MichaelisÐArbuzov reaction "Scheme 06# ð77ZOB0405Ł[ The same approach was extended to thesynthesis of other substituted isocyanates by reaction of monophosphorylated dichloromethylisocyanates with trialkyl! or dialkyl chlorophosphites "Equation "26## ð64ZOB0854Ł[ Tetraethyl"dimethylamino#methylbis"phosphonate# is methylated by dimethyl sulfate^ upon addition of gas!eous chlorine\ the resulting ylide undergoes a chlorinationÐelimination reaction to give the innersalt of triethyl chloro"trimethylammonium#methylbis"phosphonate# "Scheme 07# ð65JPR005Ł[ Theinner salt was further hydrolyzed by aqueous HCl to the corresponding bisphosphonic acid "52)#[Analogous aminophosphonic acids have been patented as herbicides ð79JAP7978109Ł[

P CCl2NCORO

RO

F

Cl

2 (RO)2PCl + Cl2FCNCO–RCl

Cl

OCN

F(RO)P(O)

Cl Cl

OCN

F(RO)P(O)

Cl(RO)P(O)(RO)2PCl

–RCl

R = Me, 42%Et, 60%

Scheme 17

Cl

OCN

X(EtO)P(O)

(Z1)(Z2)P(O)(EtO)2P X + (Z1)(Z2)P(O)CCl2(NCO)∆

X = EtO, Z1 = Z2 = Cl, 36%EtO, Z1 = Cl, Z2 = EtO, 6.5%Cl, Z1 = Z2 = Cl, 61%

(37)

NMe2

(EtO)2P(O)

(EtO)2P(O)

NMe3

(EtO)2P(O)

(EtO)2P(O)Cl

Me3N

(EtO)2P(O)

(O–)(EtO)P(O)+

+

Me2SO4

–HMeSO4

Cl2

-EtCl85%

–

Scheme 18

5[98[3[2 One Halogen and Three Phosphorus Functions

Only one representative of this family is described^ it contains one bromine and three diethylphosphoryl groups "Equation "27##[ Carbon tetrabromide reacts with triethyl phosphite undermilder conditions than does carbon tetrachloride] in re~uxing benzene the reaction is complete after0 h[ The yield of isolated product is 56) ð68ZOB0369Ł[

Br

(EtO)2P(O)

(EtO)2P(O)

(EtO)2P(O)3 (EtO)3P + CBr4

benzene

∆(38)

5[98[4 ONE HALOGEN AND TWO GROUP 04 ELEMENTS

Compounds of this class are essentially carbanions bearing `em!dinitro or diphosphorus functionsand the halogen substituent^ they occur as reaction intermediates[

5[98[4[0 Metal Halodinitromethides

The compounds described here are explosives and may detonate on grinding or impact[ Further!more\ ~uorodinitro compounds show varying degrees of toxicity and may cause painful burns whenbrought into contact with the skin[ Consequently\ they should be handled with care[

176Two Group 04

The potassium bromo! and chlorodinitromethides were prepared from the corresponding 1!halo!1\1!dinitroethanol in basic medium "Scheme 08#[ Unlike the chloro derivative which is unstable inthe free state at room temperature\ the bromo derivative can be isolated\ recrystallized\ and airdried ð53JOC2476Ł[

X = Cl, Br, 50%O2N

O2NX

O2N

O2N X K++ KOHMeOH/H2O

RTHO

–

Scheme 19

The ~uorodinitromethide was obtained by reaction of ~uorotrinitromethane with hydroperoxideions through displacement of one of the nitro groups "Scheme 19#[ The ~uorinated carbanion isunstable in solution and has been trapped by acid hydrolysis or reacted immediately ð57JOC2962Ł[The silver salt of ~uorodinitromethane is equally unstable[ It is obtained by reaction of silver oxidewith ~uorodinitromethane and reacts in situ with electrophiles to give C0C coupling reactions"Scheme 10# ð62S594Ł[

O2N

O2N

F

O2N

O2N

O2N F K+

O2N

O2N

F + H2O2 + KOHMeOH/H2O

–10 °C

H2SO4

X = Cl, Br, 50%Scheme 20

–

F

R

O2N

O2NO2N

O2N

F

O2N

O2N

F Ag+2+ Ag2O + H2Oacetone

0 °C, 18 h

R-X

RX = MeI, 53%PhCH2Br, 20%CH2=CHCH2Cl, 68%

Scheme 21

–

In contrast to the potassium and silver salts\ bis"~uorodinitromethyl#mercury is a white crystallinesubstance which is stable enough to be stored[ It reacts readily at room temperature with KI orKOH through a metal exchange reaction^ the potassium salt is formed according to Equation "28#[It is slowly hydrolyzed in the presence of moisture[ The same mercury derivative is used as a startingmaterial for the synthesis of symmetrical bis"chlorodinitromethyl#mercury by a transmercurationreaction "Equation "39##] the reaction with polynitro compounds bearing a labile hydrogen atom isperformed in moist ether at room temperature ð56DOK"065#0975Ł[

F

O2N

O2NO2N

O2N

F K+Hg + KI (or KOH) 2

2

(39)–

F

O2N

O2N

O2N

O2N

ClCl

O2N

O2NHg + 2

2

Hg

2

79%(40)

5[98[4[1 Metal Bis"phosphonyl#halomethides

Halogenated methylenebis"phosphonic acids# have biological applications which are associatedwith their complexing properties for metal cations "Ca1¦\ Zn1¦\ etc[#[ Alkali metal salts ofalkylidenebis"phosphonic acid# are known to improve the cleaning power of soaps and detergentsð55BEP561194Ł^ 0\0!bis"phosphonyl#!0!halo!0!metal derivatives are useful intermediates for the syn!thesis of substituted bis"phosphonic acids#[ The _rst preparation used a chlorineÐlithium exchange


between dichloromethylenebis"phosphonate# and butyllithium "Equation "30## ð62JOM"48#126Ł[Other metals "Na\ Tl# have been used as counterions ð74JOM"180#034\ 75JOM"298#C6Ł[

(RO)2P(O)

(RO)2P(O)Cl Li+

(RO)2P(O)

(RO)2P(O)

+ BunClBunLi

THF, –80 °C(41)

Cl

Cl–

A second approach uses a!lithio!a!chloromethylphosphonates as starting materials[ Condensationwith chlorophosphates in the presence of base "lithium diisopropylamide*LDA# a}ords the targetcompounds in quantitative yield "Equation "31## ð75JOM"293#172\ 76SC0448Ł[

Cl Li+

(RO)2P(O)

(RO)2P(O)

+ (RO)2P(O)Cl2 LDA

THF, –78 °C(RO)2P(O) Cl – (42)

Only one type of 0!halocarbanion bearing a phosphorus and a nitrogen function is known"Equation "32##[ It is used as an alkeneation reagent ð77JAP52116484Ł[

X

CN

(RO)2P(O)

X Li+

CN

(RO)2P(O)BunLi

–78 °C

X = Cl, Br

(43)–

5[98[5 ONE HALOGEN AND ONE GROUP 04 ELEMENT

Compounds of this class with a phosphorus and two silicon groups or with a phosphorus andone silicon group\ together with a lithium substituent\ have been described[ Most of them wereprepared by reaction of dichlorobis"trimethylsilyl#methane with butyllithium and a trivalent chloro!phosphane "Scheme 11 and Table 7#[ The a!chlorophosphanes shown in entries 2\ 3\ and 4 are stablecompounds\ while the analogous derivatives described in entries 0\ 1\ and 5 give spontaneouslyrearranged products at room temperature[ The product shown in entry 6 is stable at room tempera!ture\ but it rearranges to a 0!chlorophosphorane at 059>C[

TMS

TMS

Cl Li+

TMS

TMSCl

R2R1P

TMS

TMS

P

R2

Cl

R1

TMS

TMSP

TMS

TMS

TMS

ClTMS

R1R2P-ClBunLi

R1 = R2 = PhR1 = R2 = NMe2

R1 = R2 = (TMS)2CCl-Cl2C(TMS)2

Scheme 22

–

Cl

Cl

Table 7 Synthesis of chlorobis"trimethylsilyl#methylphosphanes[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐEnt R0 R1 Chlorophosphane Yield ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ0 Ph Ph Ph1PCl 72CB0031 NMe1 NME1 "Me1N#1PCl 53a 72CB0032 NMe1 Cl Me1NPCl1 57 72CB0033 Ph Cl PhPCl1 72CB0034 Cl Cl PCl2 "0 eq# 72CB0035 ClC"TMS#1 ClC"TMS#1 PCl2 "9[22 eq# 43a 71TL1906\ 75IS0066 Cl "TMS#1CH "TMS#1CHPCl1 78CB342*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐReaction conditions] −009>C\ THF:ether:pentane[ a Yields of _nal rearranged products[

178Metalloid

In a second approach\ treatment of an a!lithio!a!~uoromethylphosphonate with bromo! orchlorotrimethylsilane gives a mixture of mono and bis"trimethylsilyl# derivatives because of afacile proton transfer "Equation "33##[ These products could not be usefully separated ð72CC775\75JCS"P0#0314Ł[

F

TMS

(PriO)2P(O)

TMS F

TMS

(PriO)2P(O)(PriO)2P(O) F + TMS-Br (or TMS-Cl)

LDA

THF, –78 °C+ (44)

Only one example of a compound bearing a phosphorus\ a silicon\ a metal\ and a halogen functionon the same carbon has been described[ It was prepared from diethyl trichloromethylphosphonateby chlorineÐlithium exchange in the presence of butyllithium and chlorotrimethylsilane at lowtemperature "Equation "34##[ The compound is obtained in quantitative yield and it can either beprotonated by acids or alkylated ð77JOM"227#184Ł[

Cl

Cl

(EtO)2P(O)

Cl Cl Li+

TMS

(EtO)2P(O)BunLi

THF, –80 °C+ TMS-Cl – (45)

5[98[6 ONE HALOGEN AND METALLOID FUNCTION "THREE\ TWO OR ONE\TOGETHER WITH METALS#

5[98[6[0 One Halogen and Three Metalloid Functions

5[98[6[0[0 Three silicon functions

Organosilanes of this family have been widely investigated and several useful synthetic approacheshave been described[

The _rst one is a carbonÐhalogen bond forming reaction] tris"trimethylsilyl#methane was halo!genated by means of NBS ð57CB1704\ 60JOM"18#278Ł or bromine under UV irradiation with orwithout solvents "Scheme 12# ð81OM1827Ł[ An alternative route consists of metallation of tris!"trialkylsilyl#methanes followed by halogenation of the resulting anions "Scheme 13# ð69JOM"13#418\75CB0344\ 78JOM"255#28Ł[ Halogenating agents are tetrabromomethane or dibromodi~uoromethane[Crystal structure determinations of the silylated carbanionÐTHF adducts have been performedð72CC716\ 72CC0289Ł[

TMS

TMS

TMS

Br

TMS

TMS

TMSBenzoylperoxide

CCl4, 80 °C52%

+ NBS

TMS

TMS

TMS hν

180–190 °C75%

+ Br2 Br

TMS

TMS

TMS

Scheme 23

SiR3

TMS

TMS

TMS Li+

TMS

R3SiBr

TMS

R3Si

TMSMeLi "Br"

THF-ether

R3Si = But2HSi

But2FSi

Me2PhSi

CBr2F2CBr2F2CBr4

85%90%50%

"Br" =

Scheme 24

–

The most widely and routinely used approach is the silylation of lithiated carbanions derivedfrom `em!dihalobis"trialkylsilyl#methanes[ While chlorobis"trialkylsilyl#methanes are not suitablereagents for preparation of the corresponding carbanions\ dichlorobis! or dibromo!bis"trialkylsilyl#methanes are readily metallated through halogenÐlithium exchange reactions[ Theorganolithium derivatives thus formed react with various chlorosilanes at low temperature to give the


halotris"trialkylsilyl#methanes "Scheme 14# ð69JOM250\ 69JOM418\ 69JOM536\ 70CB1976\ 73ZAAC"409#058\75JOM"204#C4\ 76CB542\ 76CC0350\ 76JCS"P1#0936\ 78CC484Ł[ More often\ the halotris"trialkylsilyl#methanes were converted directly into new derivatives\ either by halogen substitution or by reactionsat the silicon substituents[

X

TMS

XX Li+

TMS

TMS

X

TMS

R3Si

TMSBunLi

THF, –100 °C

R3SiY–TMS

XCl

BrClBrBrClCl

ClClClCl

R3SiYTMS-Cl

TMS-ClMe2PhSiClMe2PhSiCl

(D3C)2PhSiCl(CH2=CH)Me2SiCl

Y-C6H4SiMe2FY = H, 4-MeO, 4-Cl, 3-CF3

Me2HSiClEt2HSiClMe2SiF2

MePhSiF2

Yield (%)697478-

955258-

--

5644

Scheme 25

Sodium metal may also be used to metallate dibromobis"trimethylsilyl#methane in a couplingreaction with chlorodiphenylsilane[ Bromine is then added in situ in order to perform brominationat both the carbon and silicon atoms "Scheme 15# ð78CB398Ł[ Other examples of carbonÐsiliconbond forming reactions from various starting materials have been described "Equation "35##ð66ZAAC"329#010\ 68JOM"067#00Ł[ When R0

2Si is a trichlorosilyl group and the electrophile isiodotrimethylsilane\ a signi_cant amount of bis"trichlorosilyl#trimethylsilylmethane "33)# isformed[ The same reaction was applied to the silylation of a cyclic six!membered carbosilane"Equation "36## ð68JOM"067#00Ł[ The _nal carbosilane could not be separated from the polymericside products[ The yield was established after reduction of the SiCl and CCl groups with LiAlH3[

Br

TMS

Br

SiPh2H Na+

TMS

TMS

Br

TMS

BrPh2Si

TMSNa

–2NaBr–NaCl

Br2

51%–TMS + Ph2HSiCl

Scheme 26

–

Cl

R13Si

Cl

Cl

R13Si

R23Si

R13Si

i, BunLiii, R2

3SiXR1

3Si (46)

PhMe2SiCl3SiCl3Si

PhMe2SiClTMS-I

TMS-Cl

404225

R13Si R2

3SiX Yield (%)

i, BunLiii, TMS-I

THF, –100 °C 42%

Si

Si

SiCl

ClCl

Cl

ClCl

ClCl

Si

Si

SiCl

TMSCl

Cl

ClCl

ClCl

+ polymers (47)

After reaction between TMSCCl1SiMe1Cl and butyllithium at −099>C in ether\ and subsequentwarming to 19>C\ dimeric carbosilanes are formed as the main products "Equation "37##[ Puri_cationby HPLC allowed elimination of the by!products and a}orded a mixture of the two isomersð73JOM"160#096Ł[

180Metalloid

Cl

TMS

ClMe2Si

TMSSi

Si TMS

Cl

Me Me

MeMeTMS

Cl

Si

Si Cl

TMS

Me Me

MeMeTMS

Cl

BunLi

ether, –100–20 °C+ (48)

A great number of bromotris"trialkylsilyl#methane derivatives "Table 8# have been obtained inhigh yields through further displacement of a phenyl or a hydrogen "Y# by chlorine or bromine in"YR1Si#"TMS#1CBr\ as shown in Equation "38#[ Bromine substitution reactions at the silicon atomare also e}ected by various nucleophiles "AgF\ MeOH\ AgOP"O#Ph1\ etc[#\ as shown in Equation"49# and Table 09[

Table 8 Synthesis of "XR1Si#"TMS#1CBr "X�Cl\ Br#[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR Y X Rea`ents and conditions Yield ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐMe Ph Br Br1\ 59>C\ 1 h 85 70CB1976Me Ph Cl Cll\ 69>C\ 19 h 63 70CB1976Me Ph I I1\ 029>C\ 7 h 59 70CB1976CD2 Ph Br Br1\ 59>C 71 76CB542Ph H Br Br1 85 78CB398Ph H Cl Cl1 77 78CB398But H Br Br1\ CCl3 099 75CB0344*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Br

TMS

YR2Si

TMS Br

TMS

XR2Si

TMS+ X2 + YX (49)

Br

TMS

BrR2Si

TMS Br

TMS

XR2Si

TMS+ X – + Br– (50)

Table 09 Synthesis of "XR1Si#"TMS#1CBr[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐEnt R X Rea`ents and conditions Yield ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ0 CD2 F AgF\ 59>C\ THF 56 76CB5421 Me F AgF\ 55>C\ 49 h\ THF 37 70CB19762 Ph F KHF1\ 53>C\ 1[4 h\ MeOH 78 78CB3983 Ph OH H1O\ 14>C\ 61 h\ THF 82 78CB3984 Me OH H1O\ 14>C\ 0 h\ pentane 84 70CB19765 Me MeO MeOH : Et2N\ 54>C\ 09 h 58 70CB19766 Ph MeO MeOH\ 53>C\ 5 h 89 78CB3987 Me PhO PhONa\ 000>C\ 099 h\ toluene 76 70CB19768 Me PhS PhSNa\ THF 40 70CB1976

09 Me 3!Me[C5H3SO1 AgX\ 14>C\ 3 h\ THF 77 70CB197600 Me 3!Me[C5H3SO1 AgX\ 045>C\ 0[4 h\Bu1O 64 70CB197601 Me MesSO2 AgX\ 14>C\ 3 h\ THF 79 70CB197602 Me Ph1P"O#O AgX\ 14>C\ 3 h\ THF 74 70CB197603 Me "PhO#PhP"O#O AgX\ 14>C\ 3 h\ THF 84 70CB197604 Me "PhO#1P"O#O AgX\ 14>C\ 3 h\ THF 79 70CB1976*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Chlorotris"methoxydimethylsilyl#chloromethane can be prepared from chlorotris"trimethyl!silyl#methane by addition of a large excess of ICl in tetrachloromethane\ followed by a methanolÐtriethylamine mixture "Scheme 16# ð81JCS"D#0904Ł[

Cl

TMS

TMS

TMS Cl

ClMe2Si

ClMe2Si

ClMe2Si Cl

MeOMe2Si

MeOMe2Si

MeOMe2SiICl

CCl4, 20 °C, 4 h

MeOH/Et3N

20 °C, 72 h65%

Scheme 27


5[98[6[0[1 Two silicon and a germanium function

Compounds containing two silicon functions and one germanium function have been preparedaccording to the general approaches reported above for the synthesis of halo!tris"trialkylsilyl#methanes "see Section 5[98[6[0[0#[ Thus\ chlorodimethylphenylgermane reacted withbromotris"trimethylsilyl#methyllithium at low temperature to give the corresponding germyldisilylderivative "Equation "40## ð75CB1855Ł[ Cleavage of the phenyl substituent was then performed withbromine "Equation "41##[ The colorless\ solid product was obtained in good yield[ As reportedabove for silicon "Section 5[98[6[0[0#\ the bromo function on germanium can participate in furthersubstitution reactions[

Br

TMS

Br

TMS Br

TMS

PhMe2Ge

TMS

i, BunLiii, PhMe2Ge-Cl

THF, Et2O, –110 °C 86%

(51)

Br

TMS

PhMe2Ge

TMS Br

TMS

BrMe2Ge

TMSBr2

60 °C, 2 h88%

(52)

5[98[6[0[2 Two silicon and a boron function

The only example of such compounds is bromoðbromobis"isopropyl#aminoborylŁbis"trimethyl!silyl#methane[ It is prepared by bromine addition to the corresponding methylidene!bis"isopropyl#aminoborane\ as shown in Equation "42# ð78CB484Ł[ The starting material is obtainedby the thermolysis of ð~uorobis"isopropyl#aminoborylŁtris"trimethylsilyl#methane in the gas phaseat 419>C "Equation "43##[

Br

TMS

Pri2NB

TMSPri

2NB

TMS

TMS

Br

TMS

TMS

Pri2NB

(53)

Br

+ Br2 +

79% 21%

TMS

TMS

Pri2NB

TMSPri

2NB

TMS

TMS

F520 °C

–TMS-F(54)

5[98[6[0[3 Three boron functions or two boron and a metal function

Conversion of tetrakis"tetramethylethylenedioxyboryl#methane to the corresponding tri!borylmethide anion is performed by adding two equivalents of methyllithium at low temperatureð63JOM"58#34Ł[ The lithiated carbanion is treated in situ with bromine in dichloromethane to a}ordthe crystalline bromotriborylmethane "Scheme 17#[ This last compound reacts with one equivalentof methyllithium to give the bromodiborylmethide anion^ however the conversion is incompleteunder these conditions[ The reaction of the carbanion with chlorotriphenyltin was performed butthe _nal product was not completely characterized "Scheme 18#[ An analogous iodo derivative"C2H5O1B#1"Ph2Sn#CI was more fully characterized ð62JOM"46#120Ł[ The same approach has beenapplied to the synthesis of tris"trimethylenedioxyboryl#methane derivatives ð62JA4985\ 64JOM"82#10Ł[The THF insoluble boryl substituted lithium salt was puri_ed by precipitation\ before reaction withbromine "Scheme 29#[

OB

O

OB

O

OB

OC– Li+ CBr

Br2

CH2Cl282%

3 3

2 MeLi

Scheme 28

C

4

182Metalloid

OB

O

OB

O

OB

OCBr

SnPh3

BrBr23

MeLi

2

Li+Ph3Sn-Cl

–

Scheme 29

O

B

O

CO

B

O

C– Li+

O

B

O

CBr2 BunLi Br2

CH2Cl2, –75–25 °C42%4 3 3

Scheme 30

5[98[6[1 One Halogen\ Two Metalloid\ and One Metal Function

This class of compounds contains\ principally\ bis"trimethylsilyl#lithium derivatives which havebeen studied as potential precursors for metalloid substituted carbenes[

Dihalobis"trimethylsilyl#methanes are readily metallated with butyllithium at low temperaturethrough a halogenÐlithium exchange reaction "Equation "44## ð69JOM"12#250\ 69JOM"13#536\ 69TL3582Ł[The lithium salts are stable at −009>C[ In the absence of a trapping reagent\ the salts dimerize togive tetrasubstituted ethylene derivatives ð56AG"E#30\ 61AG"E#362Ł[ They were reacted with silicon\ tin\germanium\ and phosphorus dihalogenides to a}ord 0\2!disila!\ distanna!\ or digerma!cyclobutanesð63JA5126Ł and bis"methylene#phosphoranes\ respectively ð71AG"E#79Ł[ Preparation of the analogousorganomercury reagent was carried out with "TMS#1C"Cl#Li and mercuric chloride in a 2 ] 0 ratio^the yield of ð"TMS#1ClCŁ1Hg was 47)[ The major by!product has been isolated and characterizedas a dimercury compound "Equation "45## ð69JOM"12#250Ł[

X

TMS

X

TMS X Li+

TMS

TMSBunLi

THF, Et2O, pentane–110 °C

–

X = Cl, Br

(55)

Cl Li+

TMS

TMS

TMS

Cl

TMS

TMS

Cl

TMS Hg Hg

TMS

TMS TMS

Cl

TMSHg

2

HgCl2

58% 3.4%

– +– (56)

5[98[7 ACKNOWLEDGEMENTS

In collecting the literature\ the authors have bene_ted greatly from collaboration with MrsFrancžoise Girard and Martine Rouyer\ who are gratefully acknowledged[


6.10Functions Containing Four orThree Chalcogens (and NoHalogens)ALEX H. GOULIAEVAarhus University, Arhus, Denmark

and

ALEXANDER SENNINGTechnical University of Denmark, Lyngby, Denmark

5[09[0 TETRACHALCOGENOMETHANES 184

5[09[0[0 Four Similar Chalcoèns 1855[09[0[0[0 Four oxyèn functions 1855[09[0[0[1 Four sulfur functions 2905[09[0[0[2 Four selenium or tellurium functions 296

5[09[0[1 Three Similar and One Different Chalcoèn 2975[09[0[1[0 Trioxyèn!substituted methyl chalcoèns 2975[09[0[1[1 Trisulfur!substituted methyl chalcoèns 2985[09[0[1[2 Triselenium! or tritellurium!substituted methyl chalcoèns 200

5[09[0[2 Two Similar and Two Different Chalcoèns 2005[09[0[2[0 Dioxyèn!substituted methylene dichalcoèns 2015[09[0[2[1 Disulfur!substituted methylene dichalcoèns 2015[09[0[2[2 Diselenium! or ditellurium!substituted methylene dichalcoèns 202

5[09[1 TRICHALCOGENOMETHANES 202

5[09[1[0 Methanes Bearin` Three Oxyèns and a Group 04 Element\ Metalloid or Metal Function 2025[09[1[1 Methanes Bearin` Three Sulfurs and a Group 04 Element\ Metalloid or Metal Function 2035[09[1[2 Methanes Bearin` Three Seleniums or Three Telluriums and a Group 04 Element\ Metalloid or

Metal Function 2065[09[1[3 Methanes Bearin` Three Dissimilar Chalcoèns and a Group 04 Element\ Metalloid or Metal Function 206

5[09[0 TETRACHALCOGENOMETHANES

The compounds discussed here conform to the general formula "0#\ where X is a chalcogen[

R1X1

X2R2

X4R4

X3R3

(1)

184

185 Four or Three Chalco`ens

5[09[0[0 Four Similar Chalcogens

Only the fully substituted derivatives of ortho!carbonic acid "1#\ tetrathioortho!carbonic acid "2#\and tetraselenoortho!carbonic acid "3# are of preparative signi_cance in the synthesis of tetra!chalcogenomethanes with four similar chalcogens\ ðB!69MI 509!90\ B!69MI 509!91Ł[ With just oneR group equaling hydrogen\ the lability of the compounds restricts them to being intermediates\if present at all\ in solvolytic reaction sequences\ etc[ Tetratelluroortho!carbonates "4# are unknown[Most known examples of "0# are symmetrically substituted^ acyclic as well as cyclic and spirocyclicversions of "0# have been prepared[ Examples of "0# where one or several chalcogen atoms "X�S\Se# are in a higher oxidation state than 1 are known\ but are rather rare ðB!69MI 509!91Ł[

R1O

OR2

OR4

OR3

(2)

R1S

SR2

SR4

SR3

(3)

R1Se

SeR2

SeR4

SeR3

(4)

R1Te

TeR2

TeR4

TeR3

(5)

5[09[0[0[0 Four oxygen functions

Derivatives with four oxygen functions are derivatives of ortho!carbonic acid\ C"OH#3\ and havebeen reviewed extensively ðB!69MI 509!90\ 72HOU"E3#583Ł[ The vast majority are simple ortho!esters""1# with R�alkyl or aryl\ including cyclic and spirocyclic compounds#\ but mixed ester ortho!esters""1# with R�acyl# have also been described[ The available synthetic methods can be classi_ed asinvolving basic or acidic conditions[ In the latter case simple alkanols "which readily form carbeniumions under acidic conditions and are thus subject to C0O bond cleavage# can often not be used asstarting materials[ An exception are 0!alkanols with strongly electron!withdrawing substituents"such as chlorine\ ~uorine\ or nitro substituents# in the 1!position\ where the formation of thecorresponding carbenium ions is disfavored[ Those synthetic methods which also allow the elabo!ration of unsymmetrically substitutedortho!carbonic acid esters are particularly valuable "Tables 0Ð4#[

The preparation of symmetrical ortho!carbonates "1# is possible from appropriate C0 synthons"e[g[\ tetrachloromethane "5#\ trichloronitromethane "chloropicrin# "6#\ trichloromethanesulfenylchloride "perchloromethyl thiol# "7#\ trichloroacetonitrile "8#\ trialkoxyacetonitriles "09#\ tri!chloromethyl isocyanide dichloride "00#\ aryl cyanates "01#\ and trialkoxycarbenium salts "02# andalkanols:metal alkoxides or phenols:phenoxides ð72HOU"E3#583Ł[ While the tetrasubstitution oftetrachloromethane "5# generally fails with simple alkoxides\ it does proceed satisfactorily withcopper"I# phenoxides "Equation "0## ð63TL3398Ł[ The catalytic action of iron"III# chloride permitsthe corresponding synthesis of aliphatic ortho!carbonates "1# derived from 1!~uoro and:or 1!nitrosubstituted alkanols under acidic conditions "Equation "1## ð54JOC300Ł[

CCl4 + 4ArOCuMeCN

40–60%C(OAr)4

(6) (2)

(1)

(2)CCl4 +FeCl3

–4HCl20–92%(6) (2)

OHX

XR

C(OCH2CX2R)4

Trichloronitromethane "6# and trichloromethanesulfenyl chloride "7# are more generally appli!cable as C0 synthons "Scheme 0# ð37JOC154Ł[ These reactions fail when applied to branched alkoxides[Trialkoxyacetonitriles "09# have been particularly focused upon as precursors of ortho!carbonates"1# ð66S62\ 71LA496Ł[ Trichloroacetonitrile "8# reacts with alkoxides "including branched alkoxides#via the corresponding trialkoxyacetonitriles "09# to form ortho!carbonates "1# "Scheme 1#[ Bothsymmetrical "Alk0�Alk1# and unsymmetrical "Alk0�Alk1# tetraalkyl ortho!carbonates "1# areaccessible in this way[

A broadly applicable synthesis of symmetrical tetraaryl ortho!carbonates "1# "including spirocyclicortho!carbonates derived from dihydroxyarenes# employs trichloromethyl isocyanide dichloride

186Tetrachalco`enomethanes

Table 0 Selected symmetrical acyclic ortho!carbonates C"OR#3 "1#[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR Boilin` point Meltin` point Ref[

">C:torr# ">C#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐMe 003 −4[4 66S62CF2 19[7 78JOC0889Et 048 66S62CCl2CH1 020 61S488CClF1CH1 79:1[7 54JOC300CF"NO1#1CH1 025 57USP2277036C"NO1#2CH1 052 56USP2295828CF2CF1 79 78JOC0889Pr 113 37JOC154Pri 69:09 66S62CH11CHCH1 099:00 71LA496CHF1CF1CH1 54:9[0 54JOC300CF2CF1CH1 021 78JOC0889Bu 162 37JOC154Bui 134 26JCS716CHF1"CF1#1CH1 024:9[94 54JOC300Pri"CH1#1 70Ð71:9[9990 66S62Me1CH"CH1#1 057:00 71LA496ButCH1 67Ð68 66S62CHF1"CF1#2CH1 024:9[94 54JOC300Me"CH1#4 073Ð074:1 38DOK"57#404c!C5H00 090Ð092 66S62CHF1"CF1#4CH1 069:9[997 54JOC300Me"CH1#6 131:1 −21 64FRP1124077Me"CH1#7 126Ð139:0[4 38DOK"57#404Me"CH1#8 177Ð189:1 38DOK"57#404Ph"CH1#1 098Ð009:9[997 B!69MI 509!90Ph 87 61S4882!MeC5H3 73Ð74 63TL33983!MeC5H3 090 63TL33981!ButC5H3 148Ð159 61S4881!ClC5H3 044 61S4883!ClC5H3 018Ð029 63TL33983!"O1N#C5H3 116 61S4883!"MeO1C#C5H3 001 61S488*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Table 1 Selected unsymmetrical acyclic ortho!carbonates C"OR0#2OR1 "1#[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR0 R1 Boilin` point Ref[

">C:torr#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐMe Bu 71LA496Me Bus 71LA496Me Et1N"CH1#1 71Ð72:04 71LA496Et Me 051 66S62Et Pr 53Ð55:09 71LA496Et Et1N"CH1#1 89Ð81:09 71LA496Et Ph 59Ð51:9[990 71LA496Et 3!ClC5H3 89Ð81:9[990 71LA496Bu Me 72HOU"E3#583*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Table 2 Selected unsymmetrical acyclic ortho!carbonatesC"OR0#1"OR1#1 "1#[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR0 R1 Boilin` point Ref[

">C:torr#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐMe Et 71LA496Me Bu 72HOU"E3#583Et c!C5H00 82Ð88:00 71LA496*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ


Table 3 Selected unsymmetrical cyclic ortho!carbonates "1#[

O

O

OMe

OMe

O

O

OMe

OMe

O

O

O

OMe

OMe

O

O

OEt

OEt

O

O

OPr

OPr

Compound Boiling point(°C/torr)

Ref.

71/15 84S837

62/0.15 70USP3503993

114.5/16 82LA507

123/15 64LA(675)142

147/12 64LA(675)142

Table 4 Selected spirocyclic ortho!carbonates "1#[

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O Ph

Ph

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

Compound Melting point(°C)

Boiling point(°C/torr)

145121.0–121.5

Ref.

77S7392MM3829

86JAP(K)61289091

90–94/11 77S73

84S837109–110

92MM382958

68/1.0 84S837

84S83770/5

82LA507138

138.5 77S73

82LA507138.5


Table 4 "continued#[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐCompound Boilin` point Meltin` point Ref[

">C:torr# ">C#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

O

O

O

O

O

O

O

O

O

O

O

O

But

But

O

O

O

O

O

O

O

O

O

O

O

O

111 84S837

110 67JHC166

O

O

O

O

Cl

Cl

Cl

Cl

113 72S599

156–157 86JOC370

>340 86JOC370

340 72S599

225 72S599

CCl3NO2 + 4AlkO–

(7) (2)

C(OAlk)4

CCl3SCl

(8) (2)

C(OAlk)4AlkO– 3AlkO–

CCl3SOAlk

Scheme 1

CCl3CN

(9) (2)

C(OAlk1)3OAlk2Alk1O– Alk2O–

60–80%

(Alk1O)3CCN

(10)

Scheme 2

"N!trichloromethylcarbonimidic dichloride# "00# as its C0 synthon "Equation "2## ð61S488Ł[ Thismethod is unsuitable for the preparation of aliphatic ortho!carbonates "1# "with the exception oftetrakis"1\1\1!trichloroethyl# ortho!carbonate#\ since these are cleaved by the hydrogen chlorideevolved[

(3)N

Cl

ClC(OAr)4

(11)

1,2-C6H4Cl2

170 °C66–92%

Cl3C+ 4ArOH

(2)


Aryl cyanates "01# react with alkanols under acidic conditions to form tetraalkyl ortho!carbonates"1# in 19Ð39) yield "Equation "3## ð54CB2175Ł[

ArOCN + 4AlkOH

(12) (2)

C(OAlk)4 (4)H+

20–40%

Symmetrical tetraalkyl ortho!carbonates "1# are obtained from trialkoxycarbenium tetra~uoro!borates "02# and alkoxides "Equation "4## ð45CB1959Ł[

(AlkO)3C+ BF4–

(13) (2)

C(OAlk)4 (5)AlkO–

Treatment of thallium"I# alkoxides with carbon disul_de leads to O\O?!dialkyl thiocarbonates"03#\ which react further with the starting thallium compound to yield tetraalkyl ortho!carbonates"1#\ the driving force undoubtedly being the formation of the extremely insoluble thallium"I# sul_de"Scheme 2# ð61JOC3087Ł[ Dialkoxydibutylstannanes and carbon disul_de react similarly "Scheme 3#ð60JOC0065Ł[ Thiocarbonates "03# can also be similarly desulfurized by treatment with sodiumcarbonate to yield spirocyclic ortho!carbonates "1# ð56JHC055Ł[

2RO– Tl+ + CS2

(14) (2)

C(OR)4

2RO– Tl+

–Tl2SS

RO

RO–Tl2S

Scheme 3

Scheme 4

Bu2Sn(OR)2 + CS2

(14) (2)

C(OR)4

Bu2Sn(OR)2

–Bu2SnSS

RO

RO–Bu2SnS

Carbonic acid diesters "04# can be converted to the corresponding dichloro derivatives "05# withphosphorus pentachloride^ these in turn are treated with phenols or phenoxide ions to yield tetra!aryl ortho!carbonates "1#[ Unsymmetrical ortho!carbonates "1# can also be prepared in this way"Scheme 4# ð53LA"564#031Ł[

2R2OH

–2HCl78–93%

O

R1O

R1O PCl5

–POCl3 R1O

R1O

Cl

Cl

R1O

R1O

(2)(16)

OR2

OR2

(15)

Scheme 5

Trans!esteri_cation of ortho!carbonates "1# with alkanols is another method for the preparationof ortho!carbonates\ even allowing the synthesis of unsymmetrically substituted esters[ Spirocyclicortho!carbonates are obtained with a\v!alkanediols ð66S62\ 71LA496\ 81MM2718Ł[ With equimolaramounts of a\v!diol and tetramethyl ortho!carbonate\ a half!exchanged monocyclic intermediatecan be isolated which\ with a second a\v!diol\ can form an unsymmetrical spirocyclic compound"Scheme 5# ð73S726Ł[ In principle all possible scrambling products of the trans!esteri_cation ofortho!carbonates C"OR0#3 with alcohols R1OH can be obtained "Scheme 6#[ Spirocyclic and oli!gospirocyclic ortho!carbonates "1#\ including unsymmetrical and substituted versions\ have beenprepared in considerable variety as monomers for the production of polymers ð81JAP"K#93053974Ł[Typical examples are 0\3\5\8!tetraoxaspiroð3[3Łnonane\ 0\3\5\09!tetraoxaspiroð3[4Łdecane\ 0\4\6\00!tetraoxaspiroð4[4Łundecane\ 0\4\6\01!tetraoxaspiroð4[5Łdodecane\ 0\5\7\02!tetraoxaspiroð5[5Łtri!decane\ and 7\09\08\19!tetraoxatrispiroð4[1[1[4[1[1Łheneicosane[ Trans!esteri_cation of spirocyclicortho!carbonates with diols to yield new spirocyclic ortho!carbonates "1# has also been reportedð75JAP"K#50178980Ł[


R2OHH+

C(OR2)4

R1O

R1O

(2)(2)

OR2

OR2

(2)

C(OR1)4 + R2OH

Scheme 6

Scheme 7

(2)

Alk2OHC(OAlk1)4

(2)

C(OAlk1)3OAlk2 Alk2OH

(2)

C(OAlk1)2(OAlk2)2Alk2OH

(2)

COAlk1(OAlk2)3Alk2OH

(2)

C(OAlk2)4

Simple ortho!carbonates such as tetramethyl\ tetraethyl\ and tetrapropyl ortho!carbonate can be~uorinated with helium!diluted ~uorine in a cryogenic reactor to yield the corresponding per!~uorinated ortho!esters[ The hydrogen ~uoride formed during the ~uorination is scavenged withsolid sodium ~uoride to prevent cleavage of the carbonÐoxygen bonds "Equation "5## ð76JFC"26#216\78JOC0889Ł[

(2)n = 1, 2, 3

F2/NaF

–120 °C18–56%

C(OCnH2n+1)4

(2)

C(OCnF2n+1)4 (6)

5[09[0[0[1 Four sulfur functions

Compounds "2#\ including a considerable number of heterocyclic and spiroheterocyclic tetrathio!ortho!carbonic acid esters such as 1\1!dithio substituted 0\2!dithioles and 0\2!dithianes\ werebrie~y reviewed in 0880 ð80SUL136Ł[ Tetrathioortho!carbonic acid and its tetrasodium salt are known\but they are without preparative importance[ The simplest type of organic compounds _ttingthe above description are the symmetrical tetrathioortho!carbonates C"SR#3\ available from thecorresponding alkali metal thiolate and a C0 synthon such as tetrachloromethane "5# "Scheme 7#ð72HOU"E3#694Ł[ With trichloromethanesulfenyl chloride "7# the corresponding reaction leads totetrathiomethane units containing symmetrical disul_des "RS#2CSSC"SR#2 "06# "R�Et\ Pr\ Bu\ But#in the case of aliphatic thiols "Equation "6## and trisul_des "RS#2CSSSC"SR#2 "R�Ph\ 1!ClC5H3\3!ClC5H3\ 2!MeC5H3\ 3!MeC5H3\ 1\3\5!Me2C5H1\ 3!ButC5H3# in the case of aromatic thiolsð41RTC0960Ł[ Examples of "2# are shown in Tables 5Ð8[

–4NaCl

(3)CCl4 + 4RSNa(6)

C(SR)4

RSSR + HC(SR)3

Scheme 8

–RSSR

(17)CCl3SCl + RSNa

(8)(RS)3CSSC(SR)3 (7)

Tris"methylthio#carbenium cations react with excess thiols\ RSH\ to give the correspondingtetrathioortho!carbonates C"SR#3 "Equation "7## ð57JOC2222Ł[ Unsymmetrical tetrathioortho!carbonates "R0S#1C"SMe#SR1 can be obtained from 1!"methylthio#!0\2!dithiolium cations and thi!olate anions R1S− "Equation "8## ð53ZC273Ł[ N\N?!Dinitroso!S!alkyl! or !arylisothioureas "08#\obtained in situ from isothioureas "07# and nitrous acid\ have been reported to yield unsymmetricalor symmetrical tetrathioortho!carbonates "2# with thiols and symmetrical tetrathioortho!carbonateswith base "Scheme 8 and Equations "09# and "00##[ The impossibility of obtaining tetra!t!butyltetrathioortho!carbonate C"SBut#3 in this way has been stressed[ This is probably not due to problemswith the method\ but rather to prohibitive steric congestion ð72HOU"E3#694Ł[


Table 5 Selected symmetrical acyclic tetrathioortho!carbonates C"SR#3 "2#[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR Boilin` point Meltin` point Ref[

">C:torr# ">C#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐMe 016:00 55 77S11CF2 71:69 56JOC1952Et 24[4 61RTC0006Pr 012:9[05 57JOC2222Pri 50[3 61RTC0006c!C5H00 058 70JAP"K#45014215Me"CH1#4CHMe 75MI 509!90Me"CH1#09 75MI 509!90Me"CH1#00 75MI 509!90Me"CH1#06 62GEP0583109Ph 048 61CB21793!BrC5H3 100 56BSF21223!ClC5H3 101[5Ð102[5 61CB21793!FC5H3 058 63CC5231!MeC5H3 015[2Ð016[7 61CB28943!MeC5H3 036 63CC5233!MeOC5H3 045 63CC5231!naphthyl 025 57JOC2222*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Table 6 Selected unsymmetrical acyclic tetrathioortho!carbonates C"SR0#2SR1 "2#[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR0 R1 Boilin` point Meltin` point Ref[

">C:torr# ">C#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐPri Me 74Ð75:9[1 61CB2179Ph Me 84[1Ð84[7 61CB376Ph CF2 58ZOB0644Ph 3!ClC5H3 080 02LA"285#01!MeC5H3 3!CIC5H3 082 02LA"285#0*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

(8)–3MeSH

–H[BF4] (3)[(MeS)3C]+ [BF4]– + 4RSH C(SR)4

(3)

S

SSMe+ + RS–

S

S

SR

SMe(9)

Scheme 9

NH

RS NH2

N

RS NH

NO

NO

(18)

HNO2 3RSH

–2N2, –2H2OC(SR)4

(19) (3)

N

S NH

NO

NO (10)–2N2

–2H2OC(SAlk)4

(19) (3)

Alk + 3AlkSH

N

RS NH

NO

NObase

–6N2, –4H2OC(SR)4

(19) (3)

+NH

RS NH2

(11)

(18)


Table 7 Selected cyclic tetrathioortho!carbonates "2#[

S

S

F3CS

F3CSO

S

S

F3CS

F3CS SCF3

SCF3

S

S

SMe

SMe

S

S

SMe

SMe

S

S

SMe

SPh

S

S

SMe

SC6H4Cl-4

Compound

S

S

SMe

SC6H4(NO2)-4

77CB916

77CB916

Ref.Melting point(°C)

S

S

SMe

SMe

64ZC384

64ZC384

64ZC384

67AG(E)442

SS

S S

S

64ZC384

MeS

MeS SMe

SMe

72CB3280

75RTC1

72BCJ960

(boiling point 50 °C/10 torr)

(boiling point 44 °C/5 torr)

32.7

38

63

88

S S

4-MeC6H4SO2 SO2C6H4Me-4

93

21.5 (boiling point 88 °C/0.6 torr)

148.0–148.5

(30)

(35)

Dithio! ð51RTC0998Ł and trithiomethanide ð61CB2179Ł ions can be sulfenylated with dialkyl ordiaryl disul_des to yield the corresponding symmetrical or mixed tetrathioortho!carbonates "2#"Equations "01#Ð"04##[

(12)NaNH2/NH3

C(SEt)4

(3)Na+ –[CH(SEt)2] + EtSSEt

(13)–MeSLi

C(SMe)4

(3)Li+ –[C(SMe)3] + MeSSMe

S

SS+ MeSSMe

–MeSLi S

SS

(3)

(14)

MeS–Li+


Table 8 Selected spirocyclic tetrathioortho!carbonates "2#[

S

S

S

S

CF3

CF3

S

S

S

S

S

S

S

S CF3

CF3

S

S

S

S

S

S

S

S SMe

SAc

S

S

S

S CF3

CF3

F3C

F3C

S

S

S

S

S

S

S

S

S

S

S

S

S

S

S

S

S

S

S

S

Compound Melting point(°C)

S

S

S

S

70JOC3470

Ref.

91CB2025

67JOC2567

88EUP293749

S

S

S

S

83MI 610-01

91CB2025

67JOC2567

67JOC2567

S

S

S

S

75JCS(P1)270

142–143

85.5–86.5

117.5–120.0

O

O O

O

209

165 70JHC201

44

S S

S

SS

S

O

O

O

O

Ph

120

82BCJ1106

163 76JPR(318)127

120–121 61E566

130

237–238 65LA(689)179

160.5–161.0 (dec.) 67CB767

(32)

(27)

(33)


Table 8 "continued#[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐCompound Boilin` point Ref[

">C#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

S S

S S86JOC370187–188

–CH2(SR1)2

–2R2SLi

2Li+ –[CH(SR1)2] + 2R2SSR2 C(SR1)2(SR2)2

(3)

(15)

The cyclic trithiocarbonate 0\2!dithiane!1!thione "19# has been treated with a secondary amine toform the corresponding spirocyclic tetrathioortho!carbonate "2# "Equation "05## ð51JOC3957Ł[ 0\2!Dithiolane!1!thione "12# reacts with 1!phenyloxirane "44^ R�Ph# to yield the corresponding mono!substituted 0\3\5\8!tetrathiaspiroð3[3Łnonane as a by!product "cf[ Scheme 08# ð80HCA0499Ł[

(20)S

S

S2 + HN(CH2CH2OH)2

–S=C[N(CH2CH2OH)2]2

–H2S S

S

S

S(16)

(3)

Similarly\ cyclic trithiocarbonates such as "19# and cyclic "N!cyanoimino#dithiocarbonates "10#react with a\v!alkanedithiols to form the corresponding symmetrical or unsymmetrical spirocycliccompounds "2# "Scheme 09 and Equation "06## ð56JOC1456\ 61USP2541145Ł[

(20)S

S

S +–H2S

S

S

S

S

(3)

HS SHS

S(3)

SH

S

Scheme 10

SH

(17)

(21) (3)

HS SH

S

SN

CN

n( )( )m

S

S S

Sn( ) ( )m

Carbon disul_de has been subjected to double insertion of an a!thioxo carbene leading to asymmetrical spirocyclic compound "Equation "07## ð50E455Ł[

(18)

(3)S

NN

S

S

S

S+ CS2

∆

–2N2

2

The ð1¦1Ł addition of a thioketene such as bis"tri~uoromethyl#thioketene "11# to a cyclic tri!thiocarbonate such as 0\2!dithiolane!1!thione "12# has been shown to yield the correspondingunsymmetrical spirocyclic compound "Equation "08## ð69JOC2369Ł[

(19)

(3)

+•

F3C

F3C

SS

SS

S

S

S

S CF3

CF3(22) (23)

The 1!azido!0\2!dithiole "13# decomposes in boiling dioxan with formation of the corresponding


spirocyclic tetrathioortho!carbonate "16#[ The corresponding carbene "14# "formed by loss of hydra!zoic acid# and 0\1!cyclohexanedithione "15# "formed by loss of nitrogen and hydrogen cyanide# havebeen invoked as putative intermediates "Scheme 00#[ A more rational synthesis of "16# from sodium0\1!cyclohexenedithiolate "18# and a trithiocarbenium salt "17# "Equation "19## has been developedby the same author ð65JPR016Ł[

(24) (27)

(25)

S

SN3

S

S

S

S:

S

S

S

S(26)

–HN3

–N2

–HCN19%

m.p. 162–164 °C

Scheme 11

(28) (27)

S

SSMe

S–Na+

S–Na+

S

S

S

S

(29)

EtOH

reflux, 30 min61%

++ I– (20)

The obscure reaction of methyl chlorodithioformate with methylmagnesium iodide furnishes thetetrathiepane derivative "29# "Table 7# ð64RTC0Ł[

Finally\ trans!esteri_cation of symmetrical tetrathioortho!carbonates "2# with thiols\ includinga\v!alkanedithiols\ is possible "Equation "10## ð69JHC190Ł[ A number of benzo annellated 0\3\5\8!tetrathiaspiroð3[3Łnonanes with polymerizable alkenyl side chains have been prepared in this wayð78JAP"K#90071200Ł[ Interestingly\ there is no record of the corresponding trans!esteri_cation of ortho!carbonates "1# with thiols[

(3) (3)

TsOH/C6H6(21)

HS SH S

S S

SC(SMe)4 ( )n

( )n

n( )

Treatment of 1\1!dichloro!2\3!bis"tri~uoromethyl#!0\2!dithiole "20# with 0\1!ethanedithiol leadsto the corresponding unsymmetrical tetrathiaspiro compound "21#[ The latter reacts with 0\0\0\2\2\2!hexa~uoro!1!butyne to yield 1\2\6\7!tetrakis"tri~uoromethyl#!0\3\5\8!tetrathiaspiroð3[3Łnona!1\6!diene "22#\ which is also formed by oxidation of the corresponding monocyclic sul_ne "23# with m!chloroperbenzoic acid "Scheme 01# ð80CB1914\ 83CB422Ł[

S

S CF3

CF3S

S

S

S CF3

CF3S

S

F3C

F3C

S

S

F3C

F3C

S

O

F3C CF3

HSCH2CH2SH

57%

–CH2=CH2

(32)m.p. 209 °C

(32)m.p. 209 °C

(33)m.p. 44 °C

S

SF3C

F3CCl

Cl S

S CF3

CF3S

S

mcpba

42%

(31)

(34)

Scheme 12

Of the many theoretically possible partially or fully oxidized derivatives of tetrathioortho!carbon!ates\ only a few have been prepared[ Partially ð22RTC812\ 22RTC0928Ł and fully ð00LA"273#211Ł S!brominated derivatives of symmetrical compounds are known "Scheme 02#[ The corresponding S!iodination of tetramethyl tetrathioortho!carbonate stops after the introduction of three S!iodo


functions[ Additional iodine does not attack the fourth sulfur atom\ instead it attacks the iodideions to form triiodide ions "Scheme 03#[

CHCl3C(SR)4 + 4Br2

–2Br2 EtOHSR

Br

C ( )4+

[ ] 4Br– SR

Br

(RS)2C ( )2+

[ ] 2Br– SR

O

(RS)2C

Scheme 13

( )2

(3)

[

Scheme 14

SMe

I

(MeS)2CC(SMe)4 + 2I2I2 I2

( )2+

SMe

I

MeSC[ ] 2I– ( )3+

SMe

I

MeSC] 3I–CS2

( )+

[ ] 3I3–

(3)

The disulfoxide tetraphenyl tetrathioortho!carbonate S\S?!dioxide has been prepared by solvolysisof the corresponding S\S\S?\S?!tetrabromo derivative "Scheme 02# ð22RTC0928Ł[

Disulfones "R0S#1C"SO1R1#1 ð37RTC783\ 41RTC398\ 61LA"647#021\ 71CC0072Ł and trisulfones"R0S#C"SO1R1#1SO1R2 ðB!69MI 509!90Ł are also accessible "Scheme 04#[ The disulfone "24# "Table 7#has been prepared in 77) yield by copper"II#!catalyzed copyrolysis of the corresponding cyclicdisul_de and di"p!tolylsulfonyl#diazomethane ð61BCJ859Ł[

MeSCH(SO2Me)2 + MeSO2SMe (MeS)2C(SO2Me)2

H2C(SO2Et)2 + 2 N

O

O

MeS

EtO–/EtOH

H–/THFCHCl(SO2Me)2 + PhSCl (PhS)2C(SO2Me)2

Et3N/CH2Cl2(MeS)2C(SO2Et)2

Scheme 15

The failure in a number of attempts to obtain octaoxides C"SO1R#3 of tetrathioortho!carbonates"2# has been attributed to the fact that they must be regarded as mixed anhydrides of two extremelystrong acids\ the trisulfone CH"SO1R#2 and the sulfonic acid RSO2H\ and thus subject to facilehydrolysis[

The synthesis of the sulfenic acid derivatives trisð"tri~uoromethyl#thioŁmethanesulfenyl chloride"CF2S#2CSCl and N\N!diethyl!trisð"tri~uoromethyl#thioŁmethanesulfenamide "CF2S#2CSNEt1 is par!ticularly intriguing "Scheme 05# ð65CB0865Ł[

Scheme 16

[(CF3)S]2CCl–S–NR2 + Hg[S(CF3)]2HCl

[(CF3)S]3C–S–NR2 [(CF3)S]3CSCl

5[09[0[0[2 Four selenium or tellurium functions

The chemistry of tetraselenoortho!carbonic esters "3# is not well developed^ only two compounds\tetrakis"tri~uoromethyl# tetraselenoortho!carbonate CðSe"CF2#Ł3 and tetraphenyl tetraselenoortho!carbonate C"SePh#3\ have been synthesized so far[ The former is prepared by reaction of mercury"II#tri~uoromethaneselenolate "25# with tetrabromomethane^ a contamination with 4) unreactedtetrabromomethane could not be removed "Equation "11## ð73T3852Ł[ The latter is obtained byselenenylation of tris"phenylseleno#methanide ion with diphenyl diselenide "Scheme 06# ð61CB400Ł[While this is the only reported application of this synthetic concept\ it should also be useful for thepreparation of unsymmetrical tetraselenoortho!carbonates "3#[

[(CF3)Se]2Hg + CBr4 C[Se(CF3)]465 °C

(36) (4)

(22)


C(SePh)4

PhSeSePh

THF/–40 °C89%

(4)(PhSe)3CH [(PhSe)3C]– Li+

LiN[CH2CHMe2]2

Scheme 17

No tetratelluroortho!carbonates "4# have been reported so far ðB!75MI 509!91\ B!76MI 509!90\89HOU"E01:b#0Ł[ The reason that their synthesis does not even seem to have been attempted must betheir expected instability\ with the possible exception of per~uoroalkyl tetratelluroortho!carbonates[

5[09[0[1 Three Similar and One Different Chalcogen

This category theoretically consists of thioortho!carbonates "26#\ selenoortho!carbonates "27#\telluroortho!carbonates "28#\ trithioortho!carbonates "39#\ selenotrithioortho!carbonates "30#\ tel!lurotrithioortho!carbonates "31#\ triselenoortho!carbonates "32#\ triselenothioortho!carbonates "33#\triselenotelluroortho!carbonates "34#\ tritelluroortho!carbonates "35#\ tritellurothioortho!carbonates"36#\ and selenotritelluroortho!carbonates "37#[ None of the above selenium! and:or tellurium!containing compounds have yet been reported ðB!75MI 509!91\ B!75MI 509!92\ B!76MI 509!90\89HOU"E01:b#0Ł[

R1O

OR2

SR4

OR3

(37)

R1O

OR2

SeR4

OR3

(38)

R1O

OR2

TeR4

OR3

(39)

R1S

SR2

OR4

SR3

(40)

R1S

SR2

SeR4

SR3

(41)

R1S

SR2

TeR4

SR3

(42)

R1Se

SeR2

OR4

SeR3

(43)

R1Se

SeR2

SR4

SeR3

(44)

R1Se

SeR2

TeR4

SeR3

(45)

R1Te

TeR2

OR4

TeR3

(46)

R1Te

TeR2

SR4

TeR3

(47)

R1Te

TeR2

SeR4

TeR3

(48)

5[09[0[1[0 Trioxygen!substituted methyl chalcogens

The vast majority of known thioortho!carbonates "26# are cyclic ortho!esters^ the simple compound"MeO#2CSMe has\ however\ been prepared ð72HOU"E3#692\ 89MI 509!90Ł[ Thioortho!carbonic acidtetraalkyl esters "26# have been postulated as intermediates in the preparation of tetraalkyl ortho!carbonates "1# from trichloromethanesulfenyl chloride "7# and sodium alkoxides "cf[ Scheme 0#ð37JOC154Ł[ Disul_des of the type "RO#2CSSCCl2 "38# and "RO#2CSSC"OR#2 "49# are formed con!comitantly upon treatment of 1!~uoro! and:or 1!nitroalkanols with trichloromethanesulfenyl chlor!ide "7# and base under phase!transfer conditions "Scheme 07 with\ for example\ R�"O1N#1CFCH1#ð72JOC2243Ł[

S

RO

RO

S

RO

RO

(14)

+ ROH + CCl3SCl

(8)

HO–/PTC

CH2Cl2/H2O

(RO)3CS

SCCl3

(RO)3CS

SC(OR)3

HO–/PTC

CH2Cl2/H2O

(8) (14)

ROH + CCl3SCl

+

(49)65–80%

(50)6–11%

Scheme 18


O\O!Disubstituted thiocarbonates "03# react with nitrile oxides such as "40# to give the cor!responding cyclic ortho!ester such as "41# "Equation "12## ð50AG545\ 61CB1704Ł[

S

PhO

PhO

(14)

+

(51)

(52)m.p. 79 °C

Ph CNON

S O

Ph

PhO OPh

(23)

The oxidation of 0\2!benzodioxole!1!thione "42# with lead"IV# acetate to yield the disul_de "43#is hardly a general reaction "Equation "13## ð56JCS"C#796Ł[

(53) (54)m.p. 156 °C

(24)O

OS

O

O SS

O

O

OAc AcO

lead tetraacetate

5[09[0[1[1 Trisulfur!substituted methyl chalcogens

The chemistry of trithioortho!carbonates "39# is strongly dominated by cyclic compoundsð72HOU"E3#693Ł[ See Table 09 for examples[

Spirocyclic trithioortho!carbonates "39# are accessible from 0\2!dithiole!1!thione "45# and 0\2!dithiolane!1!thione "12#\ and 1!substituted oxiranes "44#\ both possible isomers being formed intotal yields of 39Ð59) "Scheme 08# ð80HCA0499Ł[

Acyclic ð50AG545\ 61CB1704\ 80TL3218Ł as well as cyclic ð56BSF1128Ł trithiocarbonates "46# and C!sulfonyldithioformates "59# add nitrile oxides "47# to give the corresponding 0\3\1!oxathiazoles "48#and "50#\ respectively "Scheme 19# ð65CB0958Ł[ Nitrosoalkenes such as 0!nitroso!0!phenylethene "51#react with trithiocarbonates such as diphenyl trithiocarbonate to form the corresponding 3H!0\4\1!oxathiazines such as "52# "Equation "14## ð74TL1020Ł[

NO

S

PhS

PhS

+CH2Cl2

20–30 h93%

NO

SPh

SPh

SPh

(63)m.p. 124–125 °C

(62)

(25)

Pyrolysis of O\O?!alkanediyl S\S?!dimethyl bis"dithiocarbonates# "53# yields the correspondingO\S!alkanediyl S\S!dimethyl trithioortho!carbonates "54# "Scheme 10# ð67S175Ł[ Carbohydratederivatives containing cyclic trithioortho!carbonate groups have been prepared in the same wayð65S338\ 68CAR"63#016Ł^ cf[ ð65JCS"P0#1001Ł[

0!Oxa!3\5\8!trithiaspiroð3[3Łnon!1!ene derivatives "56# are accessible by S!alkylation of 0\2!dithio!lane!1!thione "12# and subsequent deprotonation to the corresponding thiocarbonyl ylide "55#\which _nally rearranges "Scheme 11# ð61BCJ0686Ł[

The trithiocarbenium salt "57# can be treated with simple primary or secondary alkanols to yieldthe corresponding trithioortho!carbonates "58# "Equation "15## ð53ZC273Ł[

S

SSMe+ –HI

(68)

R = Me, Pr, Pri

+ ROHI– S

S

OR

SMe

(69)

(26)


Table 09 Selected cyclic trithioortho!carbonates "39#[

S

O

SMe

SMe

S

O

SMe

SMe

S

O

SMe

SMe

S

O

SMe

SMe

S

O

SMe

SMe

S

S

SMe

OR

S

S

S

O R

S

S

S

O

Compound Boiling point(°C/torr)

R

78S286

S

S

S

O

78S286

Ref.

78S286

78S286

R

78S286

S

S

S

O

91HCA1500

64ZC384

91HCA1500

91HCA1500

R

110–112/4

S

S

S

O

140–142/8

(melting point 29 °C)

91HCA1500

91HCA1500

R

190–193/2

(69)

S

SS

O

R S

S

S

O

R

S

S

O

S

R

(56)S

SS

TiCl4

DCE–20 °C

+O

R

(55)S

S

S

O

(55)

R

(23)

S

S

O

S

+TiCl4

DCE–20 °C

R

(40)

+

+

(40)

(40) (40)

R = Me, CH2Cl, Et, Bu, CH2COBut, Ph

DCE = ClCH2CH2Cl

Scheme 19


R1S

R1SS R2 CNO

N

S O

R2

R1S SR1

(60)R2S

R1SO2

S +

(58)(61)

R3 CNON

S O

R3

R1SO2 SR2

(58)

+

(59)(57)

Scheme 20

MeS O O SMe

S SO S

MeS SMe

∆

90%

MeS O O SMe

S S

∆

( )n

(64)n = 2

O S

MeS SMe

(CH2)n

(64) (65)

( )n

(65)n = 2

b.p. 110–112 °C (at 4 torr)

Scheme 21

S

SS

ArBr

OS

SS

O

Ar

Scheme 22

S

SS

O

Ar+ +

MeCN

S

S

O

S

Ar

Br–

NaH

MeCN+

90%

–

(67)

(23) (66)

Bis"tri~uoromethyl#thioketene "11# adds to O\S!dialkyl dithiocarbonates "69# to form the cor!responding 0\2!dithietanes "60# in high yields "Equation "16## ð69JOC2369Ł[

(27)•

F3C

F3C

S S

R2S

R1O

F3C

F3C

S

S

SR2

OR1

+

(22) (70) (71)

5[09[0[1[2 Triselenium! or tritellurium!substituted methyl chalcogens

No compounds answering this description appear to be on record\ cf[ ðB!75MI 509!91\ B!75MI 509!92\B!76MI 509!90\ 89HOU"E01:b#0Ł[

5[09[0[2 Two Similar and Two Different Chalcogens

This category theoretically includes selenothioortho!carbonates "61#\ tellurothioortho!carbonates"62#\ selenotelluroortho!carbonates "63#\ selenodithioortho!carbonates "64#\ tellurodithioortho!


carbonates "65#\ selenotellurodithioortho!carbonates "66#\ diselenotelluroortho!carbonates "67#\diselenotellurothioortho!carbonates "68#\ ditellurothioortho!carbonates "79#\ selenoditelluro!ortho!carbonates "70#\ and selenoditellurothioortho!carbonates "71#\ none of which are knownðB!75MI 509!91\ B!75MI 509!92\ B!76MI 509!90\ 89HOU"E01:b#0Ł[

R1O

OR2

SeR4

SR3

(72)

R1O

OR2

TeR4

SR3

(73)

R1O

OR2

TeR4

SeR3

(74)

R1S

SR2

SeR4

OR3

(75)

R1S

SR2

TeR4

OR3

(76)

R1S

SR2

TeR4

SeR3

(77)

R1Se

SeR2

TeR4

OR3

(78)

R1Se

SeR2

TeR4

SR3

(79)

R1Te

TeR2

SR4

OR3

(80)

R1Te

TeR2

SeR4

OR3

(81)

R1Te

TeR2

SeR4

SR3

(82)

5[09[0[2[0 Dioxygen!substituted methylene dichalcogens

No examples of selenothioortho!carbonates "72#\ tellurothioortho!carbonates "73#\ or seleno!telluroortho!carbonates "74# are known ðB!75MI 509!91\ B!75MI 509!92\ B!76MI 509!90\ 89HOU"E01:b#0Ł[

R1O

OR2

SeR4

SR3

(83)

R1O

OR2

TeR4

SR3

(84)

R1O

OR2

TeR4

SeR3

(85)

5[09[0[2[1 Disulfur!substituted methylene dichalcogens

1\1!Dichloro!0\2!benzodioxole "75# reacts with benzenethiolate to give the dithioortho!carbonate1\1!bis"phenylthio#!0\2!benzodioxole "76# "Equation "17## ð53LA"564#031Ł[ Bis"tri~uoromethyl#thioketene "11# undergoes cycloaddition with O\O!disubstituted thiocarbonates "03# to yield thecorresponding 0\2!dithietanes "77# "Equation "18## ð69JOC2369Ł[

(28)

(86) (87)m.p. 98.5–99.5 °C

O

O

Cl

Cl

O

O

SPh

SPhPhSH/Et3N

THF

70 °C, 30 min61%

(29)S

RO

RO

F3C

F3C

S

S

OR

OR+

(14) (88)

•

F3C

F3C

S

(22)

The mercury"II# salt of N\N!bis"tri~uoromethyl#hydroxylamine\ ð"CF2#1NOŁ1Hg\ reacts with thio!phosgene with the formation of the transient corresponding O\O!disubstituted thiocarbonate\ whichin turn dimerizes to 1\1\3\3!tetrakisðbis"tri~uoromethyl#aminoxyŁ!0\2!dithietane ð73JFC"13#374Ł[

Cyclic trithiocarbonates "89# react with 2\3\4\5!tetrachloro!o!benzoquinone "o!chloranil# "78# toform spirocyclic dithioortho!carbonates "80# "Equation "29## ð62ZC354Ł[

202Trichalco`enomethanes

S

S

S

(30)O

O

S

S

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

+

(89)

O

O

(90) (91)

–[S]20–70%

Aryl N\N!dimethyldithiocarbamates with electron!withdrawing substituents in the aryl groupsuch as "81# react with methanolic sodium nitrite to form cyclic bis"dithioortho!carbonates# linkedvia a peroxide group such as "82# "Equation "20## ð68JOC156Ł[

(93)m.p. 177.0–178.5 °C(92)

NaNO2MeOH

48 h15%

O2N NO2

CF3

S NMe2

S

S

S S

SOMe MeO

OO

NO2

CF3

NO2

F3C

(31)

Tellurodithioortho!carbonates "83# and selenotellurodithioortho!carbonates "84# are unknownðB!75MI 509!91\ B!75MI 509!92\ B!76MI 509!90\ 89HOU"E01:b#0Ł[

R1S

SR2

TeR4

OR3

(94)

R1S

SR2

TeR4

SeR3

(95)

5[09[0[2[2 Diselenium! or ditellurium!substituted methylene dichalcogens

No selenium and:or tellurium compounds _tting this description appear to be on record ðB!75MI509!91\ B!75MI 509!92\ B!76MI 509!90\ 89HOU"E01:b#0Ł[

5[09[1 TRICHALCOGENOMETHANES

5[09[1[0 Methanes Bearing Three Oxygens and a Group 04 Element\ Metalloid or Metal Function

Ethyl N\N!dimethylcarbamate upon sequential treatment with triethyloxonium tetra~uoroborateand sodium ethoxide yields 25) of the corresponding acetal Me1NC"OEt#2 ð50LA"530#0Ł[ N\N\N?\N?!Tetrasubstituted ureas upon treatment with phosgene yield the corresponding formamidiniumchlorides which form the corresponding urea acetals with ethoxide[ The latter react with ethanol togive R1NC"OEt#2 ð53CB0121Ł[ Corresponding methyl compounds R1NC"OMe#2 have also beenprepared[ These compounds are remarkably stable to hydrolysis[ Transesteri_cation is possibleð72HOU"E3#609Ł\ for example of Me1NC"OMe#2 with isopropanol to yield Me1NC"OPri#2 ð66S62Ł[

N!Methyl!N\O!bis"tributylstannyl#!1!aminoethanol "85# reacts with 0\2!dioxolane!1!thione "86#to form the corresponding spirocyclic compound "87# "Equation "21## ð63JOM"61#092Ł[

(32)

(96)

Bu3SnN

OSnBu3

Me

O

OS

O

O

NMe

O

(97) (98)

+

Trialkoxycarbenium ions "typically obtained by alkylation of carbonates# react with sodiumdialkylphosphites to form the corresponding phosphonates in 48Ð57) yield\ for example "88#"Equation "22## ð77ZOB1056\ 77ZOB1057Ł[ The same products are accessible in 51Ð79) yield by


reaction of symmetrical ortho!carbonates C"OR0#3 with dialkylphosphorous acid anhydrides"R1O#1P0O0P"OR1#1 ð56ZOB1026\ 77ZOB0816Ł[ The reaction of trialkoxycarbenium ions with lithiumdialkylphosphides gives "trialkoxymethyl#phosphines such as "099# "Equation "23## ð77ZOB0336Ł[Dioxymethanephosphonates such as "090# upon electrochemical methoxylation yield the cor!responding ortho!esters such as "091# in 27Ð61) yield "Equation "24## ð76S33Ł[

(33)

(99)

[(EtO)3C]+ + (BuO)2PONa P(OBu)2

OEtO

EtO

EtO

(34)

(100)

(BuO)3C+ + Bu2PLi PBu2

BuO

BuO

BuO

(35)

(102)(101)

O

OCl

Cl

P(OPh)2

O

O

OCl

Cl P(OPh)2

OMe

O

MeOH/0.1 M MeONa

2e–

5[09[1[1 Methanes Bearing Three Sulfurs and a Group 04 Element\ Metalloid or Metal Function

Methyl N\N!dimethyldithiocarbamate after S!methylation with dimethyl sulfate and subsequenttreatment with sodium ethanethiolate forms Me1N0C"SMe#1SEt ð69BCJ2417Ł[ Aminotrithio!ortho!formates such as "093^ Z�S# have been prepared from trithiocarbenium salts and imidazolesð50LA"530#0Ł[ 1!Alkylthio!0\2!dithiolylium cations "e[g[\ 092^ Z�S# react correspondingly "Equation"25## ð69TL370Ł[ Heterocyclic aminotrithioortho!formates such as "095# are accessible by doubleaddition of 1!alkylthiiranes "094# to methyl isothiocyanate "Equation "26## ð78NKK52Ł[ A similarreaction of 1!iodoalkyl isothiocyanates with sulfur nucleophiles has been reported ð70JCS"P0#41Ł[Methyl isothiocyanate reacts with undiluted bis"tri~uoromethyl#thioketene "11# in a 0 ] 2 ratio toform the spirocyclic aminotrithioortho!formate "096# "Equation "27## ð67JOC1499Ł[ In an obscurereaction between 4!chloro!1!nitroaniline and 0\2!thiazolidine!1!thione "097#\ the correspondingbicyclic aminotrithioortho!formate "098# is formed "Equation "28## ð66USP3920117Ł[ 2\4!Dimethyl!thiazoloð1\2!bŁthiazolium bromide "009#\ upon heating with aqueous base\ forms the amino!trithioortho!formate "000# "Equation "39## ð56JOC1963Ł[ 1\2\4\5!Tetrahydrothiazoloð1\2!bŁthiazolium bromide "001# reacts with sodium benzenethiolate in ethanol to form the bicyclicaminotrithioortho!formate "002# "Equation "30##^ analogous compounds have been prepared in asimilar manner ð60JCS"C#092Ł[ The betaine "004# formed by reaction of benzo!0\2!dithiole!1!thione"003# and triethyl phosphite has been reported to interact with 0!"0!propenyl#piperidine to formthe aminotrithioortho!formate "005# "Scheme 12# ð63CB2044Ł[ The corresponding reaction withpiperidine yields the derivative "006# "Scheme 13# ð63CB2044Ł[ Thiobenzoyliminodithiocarbonatessuch as "007# have been shown to react with diphenyldiazomethane with 0\3!cycloaddition to formtwo stereoisomers of the spiro heterocycle "008# "Equation "31##\ the reaction probably taking placeby way of a thiirane intermediate ð67BCJ290Ł[

(104)(103)Z = S, Se

Et3N

MeCNS Z

Ph

SEt

+

N

NH

Ph

+ S

Z

N

SEt

NPh

Ph(36)

(37)

(106)(105)R = Me, Et

+ Me N • SS

R S

S

S

MeN

R R

2


(107)m.p. 121.5–122.5 °C

+Me N • S

(22)

•

F3C

F3C

S

S

MeN

SS

S CF3

CF3

CF3

F3C

CF3

F3C

(38)undiluted

0 °C3

(39)

(109)

+

(108)

NH2

Cl

NO2

NH

SS

N

SSS

Ar

(40)

(111)m.p. 194–194.5 °C (dec.)

N

SSS

(110)

N

SS

+

Br–

HO–/H2O

30 min67%

N

S

O

(112)

PhSNaEtOH

24 h20%

(41)N

S S

(113)m.p. 80–81 °C

Br–

+ N

S SSPh

(116)b.p. 190 °C (at 0.6 torr)

(114)

S

SS

S

SSP(OEt)3+

– S

S

N

SEtN

30%+ P(OEt)3

(115)

Scheme 23

Scheme 24

S

SS S

S

N

S

(117)

42%NH

m.p. 158 °C

55%S

S

N

SH

S

S

+

(114)

(118)

S

SN + Ph2CN2

Et2O, RT

–N251%S

Ph S

S

S

N Ph

Ph

Ph

(119)two stereoisomers

(42)


Azidotrithioortho!formates such as "010# can be obtained from trithiocarbenium salts such as "019#and azide ions "Equation "32## ð54ZC275\ 65JPR"207#016\ 70JCS"P0#507Ł[ Although azidotrithioortho!formates "011# can be isolated at low temperatures they are mostly used in situ for the elaboration ofnitrogen! and sulfur!containing heterocycles[ With triphenylphosphine\ azidotrithioortho!formates"011# form the corresponding adducts "012# "Equation "33## ð65JPR016Ł[ Trichloronitromethane "6#reacts with potassium O\O!diethyldithiophosphate with substitution of the three chlorine atomsto yield the nitrotrithioortho!formate "013# "Equation "34## ð59JAP5907088Ł[ A similar reaction oftrichloromethyl isocyanide dichloride "00# with ammonium O\O!diethylthiophosphate leads to theð"dichloromethylene#aminoŁtrithioortho!formate "014# "Equation "35## ð52BEP516375Ł[ Analogousreactions of trichloromethyl isocyanide dichloride "00# with sodium N\N!dimethyl! and N\N!diethyl!dithiocarbamate have been reported ð57BRP0986126Ł[

(120)S

S NaN3

MeCN S

S

(121)

(43)SMeSMe

N3+

ClO4–

(122)

(44)

SR3

SR1

N3 SR2

(123)SR3

SR1

N SR2NNPh3P+ PPh3

(45)

(7) (124)

Cl3CNO2 + 3(EtO)2PS2K (O2N)C[SP(S)(OEt)2]3

(46)

(11) (125)

+ 3(EtO)2POSNH4N

Cl

Cl

N

Cl

Cl

C[SP(O)(OEt)2]3

Cl3C

Bis"phenylthio#sul_ne "015# reacts with 1!diazopropane with 0\2!dipolar addition across the C1Sbond to form the corresponding thiadiazole derivative "016# "Equation "36## ð62TL2478Ł[

(47) + Me2CN2S

OPhS

PhS

(126)

NN

S

O

PhS

PhS

(127)m.p. 55 °C (dec.)

C6H6

–10 °C58%

Trisulfonylmethanes CH"SO1R#2 when treated with nitric acid:sulfuric acid yield the corres!ponding C!nitro compounds "O1N#C"SO1R#2[ In cases where R is an electron!rich aryl group\aromatic nitration takes place simultaneously ð65ZOR1472Ł[

Trithiosubstituted methanephosphonic acid diesters "020# have been prepared in 53Ð62) yieldby addition of alkanethiols to phosphonodithioformates "017#\ followed by subsequent S!alkylationand deprotonation of the asymmetrical disul_des "018# formed to the corresponding ylides "029#\which then rearrange to "020# "Scheme 14\ where LDA is lithium diisopropylamide# ð81JOC3496Ł[Methyl diethylphosphonodithioformate "021# yields the symmetrical sul_de "022# in poor yield whensubsequently treated with ethylmagnesium bromide and diethyl disul_de "Scheme 15# ð78TL2304Ł[2\3!Dicyano!0\2!dithiole!1!thione "023# reacts with trimethyl phosphite in boiling toluene to givethe corresponding 1!methylthio substituted 1!phosphonic acid dimethyl ester "024# "Equation "37##ð67JOC484Ł[

R3SH(R1O)2P

O

SR2

S

(R1O)2P

O

SSR3

SR2

(R1O)2P SR4

SR2

SR3O+

– (R1O)2P

O

SR4

SR2

SR3LDA, R4X

64–73%

(128) (129) (130) (131)Scheme 25


(EtO)2P

O

SMe

STHF

–78 °C

(132)

+ EtMgBr(EtO)2P S P(OEt)2

EtSMeS SMe

MgBr

O O

EtSSEt

–78 °C9%

(EtO)2P S P(OEt)2

EtSMeS SMe

SEt

O O

Scheme 26(133)

PhMe

reflux, 6 h15%

S S

NC CN

S

+ P(OMe)3S S

NC CN

MeS P(OMe)2

O(134) (135)

m.p. 140–141 °C

(48)

The anions of trithioortho!formates "including oligothiaadamantanes# can be silylated with tri!methylchlorosilane to yield "trimethylsilyl#trithioortho!formates "Me2Si#C"SR#2 ð56AG"E#331\ 61CB376\66CB1779Ł[ The anion of tri!t!butyl trithioortho!formate CH"ButS#2\ however\ resists trimethyl!silylation ð66CB1779Ł[ Methanetrisulfonyl tri~uoride and trimethylchlorosilane form "trimethyl!silyl#methanetrisulfonyl tri~uoride "Me2Si#C"SO1F#2 ð72ZOR68Ł[

The lithium salts of trithioortho!formates\ "RS#2CLi\ are important intermediates in a number ofsynthetic procedures[ Lithiated trithioortho!formates "including mixed compounds#*obtained bymetalation of a trithioortho!formate CH"SR#2 ð64CC105Ł\ by cleavage of a tetrathioortho!carbonateC"SR#3 with butyllithium ð61CB376Ł\ or by addition of an organolithium compound to a trithio!carbonate ð73TL880Ł*play an important role as in situ synthetic intermediates\ that is as acyl anionequivalents ð61CB2179\ 61CB2781\ 80S236\ 80TL5218\ 81BMC0596Ł and in the synthesis of tetrathioortho!carbonates "2# "see Section 5[09[0[0[1#[ In a {{one!pot|| reaction\ trithiocarbenium saltsðC"SR1#1SR0

1ŁX can be reduced with sodium borohydride and subsequently metalated with methyl!lithium to yield mixed lithiotrithioortho!formates "R0S#1"R1S#CLi ð82T2924Ł[ Isotopically labeledlithiotrithioortho!formates "RS#2CLi have also been prepared ð73HCA0972Ł[ In solution\ lithio!trithioortho!formates are in equilibrium with the corresponding dithiocarbene and lithium thiolateð56AG"E#332\ 61CB376\ 61CB2179\ 67CB2533Ł[ Silylation of lithiotrithioortho!formates leads to the cor!responding trialkylsilyl derivatives\ for example triphenyl "trimethylsilyl#trithioortho!formate\"Me2Si#C"SPh#2[

The lithium salt of tris"tri~uoromethylsulfonyl#methane\ ð"CF2#SO1Ł2CLi\ is a key electrolyte innonaqueous batteries ð82JAP"K#94951589Ł[

Sodiotrithioformates\ "RS#2CNa\ are analogously prepared from trithioortho!formates andsodium amide in liquid ammonia ð74HOU"E4#2Ł[ Like their lithium counterparts they are used in situfor synthetic purposes[

5[09[1[2 Methanes Bearing Three Seleniums or Three Telluriums and a Group 04 Element\ Metalloidor Metal Function

Triselenoortho!formates such as trimethyl triselenoortho!formate\ CH"SeMe#2 ð68JOM"066#0\70TL3998Ł\ and triphenyl triselenoortho!formate\ CH"SePh#2 ð61CB400Ł\ have been lithiated withlithium diisopropylamide and other metalation reagents[ The lithio derivatives are useful as syntheticacyl anion equivalents[

No tellurium compounds of the above description are on record ðB!75MI 509!91\ B!76MI 509!90\89HOU"E01:b#0Ł[

5[09[1[3 Methanes Bearing Three Dissimilar Chalcogens and a Group 04 Element\ Metalloid orMetal Function

1!Alkylthio!0\2!thiaselenolylium cations "e[g[\ "092^ Z�Se## probably react with imidazoles toform "093^ Z�Se# "Equation "25## ð69TL370Ł[ Subsequent treatment of 2!methyl!0\2!benzothiazol!1!one "025# with triethyloxonium tetra~uoroborate and sodium ethoxide leads to 1\1!diethoxy!2!


methyl!1\2!dihydro!0\2!benzothiazole "026# "Scheme 16# ð50LA"530#0Ł^ the corresponding reactionbetween 1!chloro!2!methyl!0\2!benzothiazolium tetra~uoroborate "027# and resorcinol "028# leadsto the spirocyclic compound "039# "Equation "38## ð57CB0026Ł[

(136) (137)b.p. 126 °C (at 1 torr), m.p. 28 °C

EtO– Na+

EtOH75%

NMe

SO

NMe

SOEt+

BF4–

NMe

S

OEt

OEtEt3O+ BF4–

CH2Cl250 °C, 3 h

98%

Scheme 27

(140)m.p. 117–119 °C

NEt3

MeCN1–2 h95%

NMe

SCl

+

BF4–

+

(138)

OH

OH NMe

S

(49)O

O

(139)


6.11Functions Containing Two orOne Chalcogens (and NoHalogens)WOLFGANG PETZGmelin-Institut der Max-Planck-Gesellschaft, Frankfurt, Germany

and

FRANK WELLERFachbereich Chemie der Universitat Marburg, Germany


5[00[1 DICHALCOGENOMETHANES 219

5[00[1[0 Methanes Bearin` Two Similar Chalcoèns 2195[00[1[0[0 Two oxyèns and a `roup 04 element and:or a metalloid and:or a metal function 2195[00[1[0[1 Two sulfurs and a `roup 04 element and:or a metalloid and:or a metal function 2115[00[1[0[2 Two seleniums or two telluriums and a `roup 04 element and:or a metalloid and:or

a metal function 2235[00[1[1 Methanes Bearin` Two Dissimilar Chalcoèns 224

5[00[1[1[0 Oxyèn\ sulfur and two functions derived from a `roup 04 element\ metalloid and:or a metal 2245[00[1[1[1 Oxyèn and selenium\ or oxyèn and tellurium and two functions derived from a `roup 04

element\ metalloid and:or a metal 2255[00[1[1[2 Sulfur and selenium\ or sulfur and tellurium and two functions derived from a `roup 04

element\ metalloid and:or a metal 225

5[00[2 MONOCHALCOGENOMETHANES 225

5[00[2[0 Methanes Bearin` One Oxyèn Function and Three Functions Derived From the Group 04Element\ Metalloid and:or a Metal 226

5[00[2[0[0 Compounds with the OCN2 core 2265[00[2[0[1 Compounds with the OCNSiTa core 2265[00[2[0[2 Compounds with the OCPSiTa core 2275[00[2[0[3 Compounds with the OCFe2 core 2275[00[2[0[4 Compounds with the OCCo2 core 2395[00[2[0[5 Compounds with the OCW2 core 2315[00[2[0[6 Compounds with the OCRu2 core 2325[00[2[0[7 Compounds with the OCOs2 core 2335[00[2[0[8 Compounds with the OCFe1Ni core 2355[00[2[0[09 Compounds with the OCFe1Co core 2355[00[2[0[00 Compounds with the OCFe1Rh core 2365[00[2[0[01 Compounds with the OCFe1Mn core 2365[00[2[0[02 Compounds with the OCRu1W core 2375[00[2[0[03 Compounds with the OCW1Ru core 237

5[00[2[1 Methanes Bearin` One Sulfur Function and Three Functions Derived from the Group 04Element\ Metalloid and:or a Metal 237

208

219 Two Or One Chalco`ens

5[00[2[1[0 Compounds with the SCN2 core 2375[00[2[1[1 Compounds with the SCSi2 core 2385[00[2[1[2 Compounds with the SCSi1P core 2495[00[2[1[3 Compounds with the SCPSiLi core 2405[00[2[1[4 Compounds with the SCSi1Li core 2405[00[2[1[5 Compounds with the SCN1Fe core 2405[00[2[1[6 Compounds with the SCNSnPt core 2405[00[2[1[7 Compounds with the SCSiSnLi core 2405[00[2[1[8 Compounds with the SCFe2 core 2415[00[2[1[09 Compounds with the SCCo2 core 2415[00[2[1[00 Compounds with the SCFe1Co core 2415[00[2[1[01 Compounds with the SCCo1W core 242

5[00[2[2 Methanes Bearin` One Selenium or One Tellurium Function and Three Functions Derivedfrom the Group 04 Element\ Metalloid and:or a Metal 243

5[00[2[2[0 Compounds with the SeCN2 core 2445[00[2[2[1 Compounds with the SeCSi2 core 2445[00[2[2[2 Compounds with the TeCSi2 core 245

5[00[0 INTRODUCTION

The compounds in Chapter 5[00 are discussed as follows] _rst those compounds with a group 04element at the carbon atom^ second those compounds with metalloids "other main group elements#^and _nally transition metal functions[ Compounds with dissimilar atoms at the carbon atom arediscussed after compounds with similar atoms[

5[00[1 DICHALCOGENOMETHANES

5[00[1[0 Methanes Bearing Two Similar Chalcogens

Dichalcogenomethanes with similar chalcogens and further atoms other than chalcogens orhalogens have only been described with the O1C\ S1C\ and Se1C units^ compounds with the Te1Cunit could not be found[

5[00[1[0[0 Two oxygens and a group 04 element and:or a metalloid and:or a metal function

Up to 0884\ compounds with the "RO#1C unit bonded to group 04 elements other than N havenot yet been described[ Compounds in which this unit is connected to metalloids or metal functionscould also not be found[

"i# Compounds with the O1CN1 core

Compounds with the O1CN1 core are urea acetals and the chemistry of these compounds andother O! and N!functional orthocarbonic acid derivatives has been reviewed by Kantlehner et al[ð66S62Ł[

No common method exists to prepare all these types of compounds\ but there are some generalprocedures[ As illustrated in Scheme 0\ Meerwein has reported that various dialkyl!aminoethoxycarbenium tetra~uoroborates can be reversibly converted into the acetals "0# bytreatment with anhydrous NaOEt in acetonitrile ""0a#\ 45)^ "0c#\ 54)^ "0d#\ high#^ with BF2^reconversion into the water!soluble salts occurs quantitatively[ The preparation of the acetals "0#

210Dichalco`enomethanes

cannot be performed in alcohol because in this solvent one NMe1 group is readily replaced to giveR1NC"OEt#2 compounds ð50LA"530#0Ł[

OR

Me2N

Me2N

Me2N

Me2N OR

OR

N

N

Me

OEt

Me

N

N

Me

Me

OEt

OEt

N

N

Me

OEt

Me

+

+

N

N

Me

Me

(1)

NaOR

a; R = Etb; R = Me

+

OEt

OEt

(1c)

NaOEt

(1d)

NaOEt

Scheme 1

Compound "0a# and the corresponding methoxy derivative "Me1N#1C"OMe#1 "0b# are obtainedby reacting NaOR in a similar procedure with ð"Me1N#1CClŁCl ð53CB0121Ł\ "Me1N#1CF1 ð66S62Ł\ or"Me1N#1C"OR#CN ð71LA496\ 89LA854Ł^ the compounds are also formed as a side product during thepreparation of the triamine "Me1N#2COR in a one!pot reaction from the formamidinium chlorideð"Me1N#1CClŁCl and HNMe1 "to give ðC"NMe1#2ŁCl and ðH1NMe1ŁCl# followed by treating themixture with NaOR in THF^ the alcohol formed reacts further with the triamine to give "Me1N#1C"OMe#1 or "Me1N#1C"OEt#1\ respectively ð68LA1978Ł[ The reactions are shown in Scheme 1[

NaOR

OEt

Me2N

Me2N

+

Me2N

Me2N OR

CNCN–

Cl

Me2N

Me2N

+ Cl–

Me2N

Me2N OR

OR

(1)

NaOR

Me2N

Me2N F

F

Me2N

Me2N OR

NMe2

NMe2

Me2N

Me2N

+–OR

HOR

Scheme 2

The _rst report about acetals with the O1CN1 core appeared in 0848 in a short note by Stachel[As depicted in Scheme 2\ alcoholysis of the cyclic N\N?!diacylurea dichloride derivative\ which hasbeen obtained from oxalyl chloride and diisopropylcarbodiimide\ produces the correspondingacetals "0# ""0e#\ R�Me\ m[p[ 014>C^ "0f#\ R�Et\ m[p[ 036>C#[ With ethylene glycol the stablespiroacetal "0g# "m[p[ 134>C\ dec[# is formed ð48AG135Ł[

Whereas the methods in Schemes 0 to 2 comprise alcoholysis of diaminodihalogenomethanes\acetals can also be produced by aminolysis of dioxodihalogenomethanes[ Thus\ 1\1!dichloro!0\2!benzodioxole in ether reacts with piperidine ð53LA"564#031Ł or morpholine ð61G447Ł with cooling to


N

N

O

OO

O

Pri

Pri

(1g)

N

NO

O

Pri

Pri

Cl

ClN

NO

O

Pri

Pri

OR

OR

(1e, f)

HORHO

OH

Scheme 3

give the corresponding acetals "1a# and "1b# in 73) and 61) yield\ respectively ""1a#\ m[p[ 73Ð74>C^ "1b#\ m[p[ 019Ð011>C# "Scheme 3#[

O

O N

N

O

O

(2b)

O

O N

N

(2a)

O

O Cl

Cl

NH

O

NH

Scheme 4

A more complicated procedure for the preparation of acetals is based on the extrusion of "Bu2Sn#1Sduring the reaction of N\N?!bis"tributylstannyl#!N\N?!dimethylethylenediamine with ethylenethionocarbonate in chloroform to form the spiroacetal "2# in 76) yield "b[p[ 68Ð78>C:3 mm Hg#[Analogously\ the symmetrical acetal "3# "b[p[ 30>C:0 mm Hg# was obtained in 89) yield by react!ing the bifunctional organotin compounds O\N!bis"tributylstannyl#!N!methylethanolamine with2!methyl!1!oxazolidinethione[ The compounds have been puri_ed by distillation ð69MI 500!90Ł"Scheme 4#[

N

N

O

O

Me

O

OS

MeN

N

Me

SnBu3

Me

SnBu3 +

Scheme 5

(3)

(4)

O

N

N

O

Me

Me

OSnBu3 +

N

Me

O

N

Me

S

The structure of the anhydronucleoside "4# has been con_rmed by x!ray structure analysis[ Thecompound was obtained in 54) yield by treatment of the epoxide "a mixture of isomers# with BF2

etherate in THF at room temperature[ Compound "5# was crystallized by slow evaporation ofacetoneÐacetonitrile solution ð70CC679Ł[

5[00[1[0[1 Two sulfurs and a group 04 element and:or a metalloid and:or a metal function

Most of the compounds in this section are based on the coordination chemistry of the fragmentS1CPR2 in which the two sulfur atoms and the carbon atom interact with a mononuclear or dinucleartransition metal fragment in an allyl!like manner[ Compounds with the S1CPMo\ S1CPW\ andS1CPMn core have been described[ The coordination mode of the S1CPR2 ligand has been studiedð82OM3156Ł[


O O

OO

N

N

O

NHAc

(5)

O O

O

N

(6)

NO

O

NHAc

"i# Compounds with the S1CN1 core

There are only few compounds described in the literature with the S1CN1 core and because of thedi}erent natures of the compounds a common method of preparation for these compounds cannotbe formulated[

The starting materials for the preparation of "PhS#1C"NO1#1 "6# are various highly reactive ylides^these are treated with benzensulfenyl chloride as shown by pathways "a#Ð"d# in Scheme 5[ Thus\ theylide Me1S¦

0C−"NO1#1 in acetonitrile or dichloromethane "pathway "a## with 1 moles of PhSCl atroom temperature produces "6# "colorless crystals\ m[p[ 50Ð51>C# in 59) or 39) yield\ respectively[It was assumed that the salt "7# is formed in the _rst step\ which is further converted into "6# withthe liberation of Me1SCl1[ With the ylide Ph1S¦

0C−"NO1#1 under similar conditions "pathway"b##\ "6# was obtained in 81) yield ð64IZV1510\ 66IZV028Ł[ Similarly\ the selenium dinitro ylidePh1Se¦

0C−"NO1#1 was reacted "pathway "c## to give "6# in 74) yield with removal of the seleniumas Ph1SeCl1[ Puri_cation was achieved by extraction of the dried reaction mixture with hot heptanefollowed by cooling with dry ice ð67IZV0980Ł[ The iodonium ylide PhI¦

0C−"NO1#1 in ether produces"6# in only 19) yield "pathway "d## along with PhSC"NO1#1Cl "34)#^ the compounds were separatedby preparative TLC ð65IZV1539\ 67IZV1237Ł[

Me2S

NO2

NO2

–

+

Ph2Se

NO2

NO2

–

+Ph2S

NO2

NO2

–

+

PhI

NO2

NO2

–

+

NO2

NO2

PhS

Me2S

PhSCl

PhSCl

PhSCl

(b)

PhSCl

PhSCl

(c)

NO2

NO2

PhS

PhS

(8)

(7)

Cl

(a)

(d)

Scheme 6

Thiourea derivatives such as S1C"NHAc#1 containing electron!acceptor substituents on nitrogenundergo a radical S!arylation by phenyl radicals "generated from N!nitrosoacetanilide# to generatethe radical ðPhSC"NHAc#1Ł = [ Decomposition produces further radicals from which "8# "m[p[ 099Ð094>C# could be isolated as a product of recombination in 05) yield "Equation "0##[ The reactionwas carried out in acetone followed by addition of alcohol ð71IZV359Ł[


PhS + PhS

NHAc

NHAc

NHAc

NHAc

PhS

PhS

(9)

(1)

Yellow crystals of "09# "m[p[ 034Ð035>C# have been obtained in 10) yield by reacting 1!methyl!cyclopentanone with CS1 in aqueous ammonia at 9>C[ The product was puri_ed by recrystallizationfrom acetic acidÐwater ð62JCS"P0#0998Ł "Equation "1##[

N SH

NH2

SH

(10)

CS2, NH4OHO (2)

Compound "00# was shown by NMR spectroscopic studies to be formed when the trimerizationproduct of 1 moles of MeN1C1S and 0 mole of MeN1C1O was allowed to react with ethyleneoxide as depicted in Equation "2# ð52BAU0273Ł[ The preparation of "01# has also been describedð57MI 500!90Ł[

N N

NS S

O

Me Me

MeO

N N

NO

O

Me Me

Me

S

S

(11)

(3)

N

N

N

N

S

S

PhO

O

O

PhO

O

O

Cl

Cl

(12)

The cyclic cationic cobalt carbene complex "02# reacts with CS1 in acetone "1 h at 59>C# to thedark brown dimetallaspirocarbene complex "03# as depicted in Equation "3#^ the structure of thecompound was con_rmed by x!ray analysis[ The dication was obtained in 47) yield as the PF5 saltand crystallizes with 9[4 mole of acetone ð74CB2040Ł[

(4)Co S

N

N

CoS

Me

Me

Cp

Me3P

Cp

PMe3Co

O N Me

PMe3

Cp

(14)(13)

2

CS2

2++

"ii# Compounds with the S1CP1 core

There are only three quite di}erent compounds known with the S1CP1 core[ The 0\2!dimethyl!1\1\3\3!tetrakis"trimethylsilylsulfano#!0\2!diphosphetane "04# "m[p[ 009>C# has been prepared in68) yield from the reaction of methylbis"trimethylsilyl#phosphine with CS1 in 0\1!dimethoxyethaneat −29>C[ In the _rst step CS1 inserts into the starting material and the insertion product dimerizesto "04#[ The compound crystallizes from cyclopentane at −67>C as shown in Equation "4#ð73ZAAC"406#64Ł[


Me P

TMS

TMS

P

P

Me

Me

S

S

TMS

TMS

STMS

STMS

(15)

(5)CS2

The dithioacetal "05# is formed in 84) yield by sulfenation of the corresponding methylenecompound with MeSSO1Me[ The starting materials were adsorbed on Al1O2ÐKF and left at roomtemperature for 0 h according to Equation "5#[ The compound was extracted with dichloromethaneand puri_ed by chromatography ð81SC0248Ł[

O

(EtO)2P

(EtO)2P

O

SMe

SMe

(16)

O

(EtO)2P

(EtO)2P

O

(6)Al2O3–KF

MeSSO2Me

Green crystals of the cationic complex "06# form in 39) yield from a hot mixture of MeC!"CH1PEt1#2 "triphos# and Fe"BF3#1 = 5 H1O in dichloromethaneÐethanol when CS1 is passed throughthe solution ð79AG0944\ 70JOM"107#70Ł[

P

P

EtEt

EtEt

S

SP

EtEt

P

Fe

PEtEt

Et Et(17)

[BF4]2–

2+

"iii# Compounds with the S1CSi1 core

The compounds of the type "R0S#1C"SiMe1R1#1 "07# have been prepared by three related methods[The methods described in Table 0 start from various lithium salts[ Method 0 is the reaction of"TMS#1CLi1 with 3 moles of MeSSO1Me in at −67>C in THF ð77TL4126Ł[ Method 1 is the reactionof the corresponding "RS#1CH1 with BuLi followed by addition of RMe1SiCl to give _rst "RS#1CH!"SiMe1R#\ which is again treated with BuLi:RMe1SiCl ð89CL0300Ł[ A similar procedure generatesthe heterocycles "07e# and "07f# ð56JA320\ 56JA323Ł[ Method 2 is the reaction of "TMS#1C"SPh#Liwith PhSSPh in THF ð73JOC057Ł[ The compound "07a# forms also as an equimolar mixture with"TMS#1C1O during the reaction of "TMS#2CSMe with mcpba at −67>C in dichloromethaneð75TL4874Ł[

Table 0 Preparation of "R0S#1C"SiR12#1\ compounds "07a#Ð"07f#[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ"07# R SiR0

2 M[p[ Method Yield Ref[">C# ")#

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐa Me TMS 0 74 77TL4126b Me SiMe1Ph 1 59 89CL0300c Et TMS 1 89CL0300d Ph TMS 1\ 2 61\ 50 73JOC057e 0"CH1#20 TMS 18[5Ð29 1 85 56JA323f 0"CH1#20 SiPh2 106 1 56JA320*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

The compound "TMS#1C"SH#SOEt was proposed to be an intermediate during the thermaldecomposition of "TMS#1CHSSOEt to give _nally TMS!C"S#SEt via a sila!Pummerer typerearrangement ð74TL1148Ł[


"iv# Compounds with the S1CGe1 core

The germanium derivative "08#\ analogous to the heterocycles "07e#\ has been prepared in a similartwo!step procedure as described in method 1 in Table 0 ð56JA320Ł[

S S

Et3Ge GeEt3

(19)

"v# Compounds with the S1CSn1 core

One compound of this type is described in the literature[ Colorless crystals of "MeS#1C"SnMe2#1"19# "m[p[ 80Ð81>C# have been obtained in 89) yield by addition of ClSnMe2 to a solution of"MeS#1"Me2Sn#CLi in THF at −67>C[ The compound was puri_ed by vacuum distilation ð66CB730Ł[

"vi# Compounds with the S1CNa1 core

Only one compound with this core\ "PhOSO1#1CNa1\ has been mentioned in the literature ð57MI500!90Ł^ nothing is reported about the nature of the C0Na bond[

"vii# Compounds with the S1CNSi core

The compound "MeS#1C"N1CHPh#TMS "10# has been obtained by the reaction ofPhCH1N1C"SMe#1 with lithium diisopropylamide "LDA# in THF at −67>C followed by additionof TMS!Cl together with the silylated product PhCH1N1C"SMe#"SCH1TMS#[ The compoundratio varies between 29:69 and 64:14 as monitored by NMR spectroscopy and depends on the timewhen TMS!Cl was added to the reaction mixture^ chromatography over silica gel with petroleumether:benzene produces "10# in 7) yield ð64AG338\ 79LA0640Ł[

"viii# Compounds with the S1CPSi core

Mikolajczyk and co!workers describe the formation of "MeS#1C"P"1O#"OEt#1#"TMS# "11#\ whenthe salt ð"MeS#1C"P"1O#"OEt#1#ŁLi is treated with TMS!Cl in THF at −67>C[ The compound wascharacterized by a 20P NMR signal at d�26[3 ppm ð78S090Ł[

"ix# Compounds with the S1CSiGe core

The only compound with this core has been reported by Brook et al[ In a procedure describedfor the heterocycles "07e#\ "07f#\ and "08#\ the 1\1!disubstituted 0\2!dithiane "12# has been obtainedin two steps by lithiation of the 1!germyl!0\2!dithiane followed by addition of TMS!Cl "method 1for "07## ð56JA320Ł[

S S

Et3Ge TMS

(23)

"x# Compounds with the S1CSiLi core

The structure of compounds with this core is not reported[ Ionic "ð"RS#1C"SiR2#ŁLi# or covalentformulation is possible[ Reich reported a low!temperature multi!NMR study involving


"PhS#1C"SiMe1 Ph#Li "and similar compounds#[ In THFÐether the compounds are present as contaction pairs\ whereas in hexamethylphosphoric triamide "HMPTA# weakening of the C0Li bondoccurs with formation of separated ion pairs ð82AG0378Ł[

The compounds have generally been obtained by treating the corresponding "RS#1C"SiR2#H withBuLi or a lithium amide in a polar solvent such as THF or diethyl ether[ Thus\ a solution of"MeS#1C"TMS#Li is obtained by addition of "MeS#1C"TMS#H to a solution of LDA in a mixture ofTHF\ hexane\ and HMPTA at −67>C ð66CB730Ł[ Similarly\ addition of BuLi to a THF solution at−69 to −49>C of the appropriate "RS#1C"SiR2#H species can also be achieved ð62CB1166Ł[

In most cases the compounds have been generated in situ and used as nucleophiles to producean elementÐcarbon bond in the reaction with elementÐhalogen compounds[ The following specieshave been used in this manner] "MeS#1C"TMS#Li ð62CB1166\ 64AG26\ 72JA6608\ 74TL2920\ 78TL6922\89CL0300Ł\ "PhS#1C"TMS#Li ð73JOC057Ł\ "MeS#1C"SiMe1Ph#Li\ "EtS#1C"TMS#Li\ "EtS#1C"SiMe1

Ph#Lið89CL0300Ł\ "MeS#1C"SiMe1But#Li ð74TL0892Ł\ "SCH1CH1CH1S#C"TMS#Li\ and "SCH1SCH1

S#C"TMS#Li ð62CB1166Ł[

"xi# Compounds with the S1CSnLi core

The compounds "MeS#1C"SnPh2#Li\ "MeS#1C"SnBu2#Li\ and "MeS#1C"SnMe2#Li have beenobtained by reacting "MeS#1CHLi with the corresponding R2SnCl compounds followed by treatingof the resulting "MeS#1CHSnR2 with LDA in THFÐHMPTA at −67>C ð64AG26Ł[ The compound"MeS#1C"SnMe2#Li has similarly been prepared in a THFÐhexaneÐHMPTA mixture ð66CB730Ł[ Inall cases the compounds were used in solution for further reactions[

"xii# Compounds with the S1CPCr core

The compound "PhS#1C"PPh2#Cr"CO#4 "13# was presented at a symposium without further detailsof its preparation ð64JOM"83#118Ł[ The compound can be considered to result from the coordinationof the ylide "PhS#1 C1PPh2 to the 05!electron fragment Cr"CO#4 via the carbon atom[

(CO)5Cr

SPh

SPh

PPh3

(24)

"xiii# Compounds with the S1CPMo core

The coordination chemistry of the adduct S1CPR2 "R�Me\ Et\ cyclohexyl "Cy## towards variousmolybdenum compounds has been explored by the group of Miguel\ Carmona and others[ Thisligand coordinates in a h2!pseudoallylic manner to one or two transition metals or to one transitionmetal and a main group element with formation of a S1CPMo core[

The _rst compound in this series\ the dimeric species "Mo"CO#1"S1CPEt2#"PEt2##1 "14#\ has beendetected by Bianchini and prepared either from Mo"CO#2"C6H7# and S1CPEt2 or from irradiatingthe h0!bonded complex "CO#4MoS1CPEt2 in 59) and 39) yield\ respectively ð71OM667Ł[ Theaddition of SnBuCl2 to "14# leads to "15# "58) yield# in which the two sulfur atoms form bridges tothe tin atom ð81AG70Ł^ the reactions are summarized in Scheme 6[

Red crystals of "16# have been obtained by two routes[ Starting from MoHCl"CO#1"PMe2#2 thecomplex is formed in low yield with CS1 by elimination of HCl[ The compound is also formed inan unusual reaction on heating a solution of Mo"C1S3#"C1H3#"PMe2#2 at 49>C under 1 atm CO[Alkylation leads to the cationic species "17# as depicted in Scheme 7 ð81JCS"D#1296\ 82IC4458Ł[

The related mononuclear compound "18# is produced in 64) yield by insertion of CS1 into theMo0P bond of MoCl"NO#"PMe2#3[ Replacement of Cl and one PMe2 by the chelating ligandðS1CNMe1Ł− results in the formation of the yellow complex "29# in about 49) yield as shown inScheme 8 ð78IC1019Ł[


SMo

S

Mo

S

S

PR3

R3PCO

PR3

CO

PR3

OCOC

Mo(CO)3C7H8 (CO)5MoS2CPEt3S2 CPEt3 UV, THF

(25) R = cyclohexylR = EtR = Bu

S

Mo

SPR3

COPR3

COSnCl

Cl

Cl

Bu

NCMe

Mo

NCMe

CO

CO

Cl

OCSn

Cl

Bu

ClS2CPR3

(26)

SnBuCl3

Scheme 7

S

Mo

SPMe3

(27)

COCO

Me3PMe3P

S

Mo

SPMe3

(28) R = Me, Et

COCO

Me3PMe3P

R

RI

CS2 COMo(C2S4)C2H4)(PMe3)3MoH(Cl)(CO)2(PMe3)3

+

Scheme 8

S

Mo

SPMe3

(29)

NOPMe3

Me3PCl

CS2MoCl(NO)(PMe3)4

Na[S2CNMe2]

(30)

S

Mo

SPMe3

NOPMe3

SS

Me2N

Scheme 9

Dinuclear compounds\ in which the S1CPR2 group is bridging to another transition metal via thesulfur atoms\ have been realized with Mn!\ Re!\ and Ru!containing fragments[ Thus\ reaction of"CO#2"Br#Mn"S1CPR2# with Mo"CO#2"NCMe#2 in THF produces the purpleÐred complex "20# inquantitative yields as shown in Scheme 09 "M�Mn#[ One CO group at the Mo atom can bereplaced by monodentate phosphines to give "21# ð80JOM"319#C01\ 82OM0283Ł^ whereas the action ofchelating ligands R1PEPR1 "E�O\ R�Et^ E�CH1\ R�Me\ Ph# produce red "22# in 69Ð79)yield ð82OM0283Ł[ Reduction of "20# with Na0Hg in THF produces the anion "23#\ probably with


formation of a Mo0Mn bond ð82OM1777Ł[ The analogous Re!containing compounds "20Ð23^M�Re# have been obtained ð83JOM"356#120Ł[

SPR3

COCO

Br

MCOCO

CO

COMo

S

(31)

SPR3

COCO

MCOCO

CO

COMo

S

(34)

SPR3

LCO

Br

MCOCO

CO

COMo

S

(32)

SPR3

PR2

COBr

MCOCO

CO

COMo

S

R2PE

(33)

MS

SBr

CO

PR3

CO

CO Mo(CO)3(NCMe)3 Na/Hg

LR2P

EPR2

a; E = O; R = Etb; E = CH2; R = Mec; E = CH2; R = Ph

Scheme 10

If the starting complex Mo"CO#2"NCMe#2 is treated with the cationic species ð"h!Me5C5#ClRuC"S1CPCy2#Ł¦ in THF\ "24# is formed instantaneously as depicted in Scheme 00[ This complexundergoes substitution of one CO group to a}ord the cationic dicarbonyls "25#^ all compounds havebeen prepared as the PF5

− salts ð81POL1602Ł[

RuS

SPCy3

Cl

Cy = cyclohexyl

+ +

(36) a; L = PEt3b; L = P(OMe)3

+

Mo(CO)3(NCMe)3

SPCy3

LCO

Cl

Ru COMo

SS

PCy3

COCO

Cl

Ru COMo

S

Scheme 11

L

(35)

A further series of compounds with the S1CPMo core is depicted in Equation "6#[ The reactionof "h2!allyl#"CO#1BrM"h1!S1CPR2# "M�Mo\ W^ R�cyclohexyl\ Pri# with Mo"CO#2"NCMe#2 indichloromethane produces a series of four compounds of the type "26# with M?�Mo\ M�Mo orW in yields up to 89) ð83OM0225Ł[

MS

SPR3

Mo(CO)3(NCMe)3

S PR3

COCO

Br

M1 COM2

S

(37)

Br

COCO

CO

CO

(7)

M1 = Mo, WM2 = Mo, WR = Cy, Pri


"xiv# Compounds with the S1CPW core

There are only few compounds with this core which resemble those of the corresponding Mocompounds[ Thus\ the series of four compounds "26# in Equation "6# have also been obtained withM?�W ð83OM0225Ł[ The reaction sequence shown in Scheme 00 under similar conditions withW"CO#2"NCMe#2 leads to the corresponding cation "27# and the substitution product "28#ð81POL1602Ł[

+SPCy3

COCO

Cl

Ru COW

S

(38)

+SPEt3

PEt3CO

Cl

Ru COW

S

(39)Cy = cyclohexyl

Starting with WHCl"CO#1PMe2\ the red complex "39# is formed in 79) yield by reacting withCS1^ HCl is eliminated[ This compound can be transferred into the cationic species "30# in 49)yield upon alkylation with MeI^ the corresponding reaction of the analogous Mo compounds isdepicted in Scheme 7 ð82IC4458Ł[

S

W

SPMe3

(40)

COCO

Me3PMe3P

S

W

SPMe3

(41)

COCO

Me3PMe3P

Me +

The tungsten ylide compound "PhS#1C"PPh2#W"CO#4 "31# was presented at a symposium withoutfurther details of preparation ð64JOM"83#118Ł^ it is the tungsten analogue of the chromium complex"13#[

(CO)5W

SPh

SPh

PPh3

(42)

"xv# Compounds with the S1CPMn core

Compounds with this core are only known with the S1CPR2 ligand bonded in a h2!manner andbridging two transition metals[ Starting with the ionic compound "23# "M�Mn# in which the ligandis h2!bonded to the Mo atom\ the reaction with ClSnPh2 in THF induces a change in the coordinationmode and leads to the red compounds "32# "R�cyclohexyl\ Pri# in 69Ð79) yield ð82OM1777Ł[

SPR3

COCO

MoCOCO

CO

COMn

SPh3Sn

(43)

The heterobimetallic compound ReMn"CO#5S1CPCy2 "33#\ in which the Mo"CO#2SnPh2 fragmentof "32# is replaced by the isoelectronic Re"CO#2 fragment\ is obtained in 43) yield either by thereaction of "CO#2BrMn"h1!S1CPCy2# or the cation ð"CO#3Mn"h1!S1CPCy2#Ł¦ with NaðRe"CO#4Ł in


THF or by the reaction of "CO#2BrRe"h1!S1CPCy2# with NaðMn"CO#4Ł as shown in Scheme 01ð80OM273Ł[

SPR3

COCO

ReCOCO

CO

COMn

S

MnS

SBr

CO

PCy3

CO

CO

(44)

ReS

SBr

CO

PCy3

CO

CO

MnS

SCO

CO

PCy3

CO

CO

+

Na[Re(CO)5] Na[Mn(CO)5]

Na[Re(CO)5]

Cy = cyclohexyl

Scheme 12

The preparation of a series of homobinuclear compounds starting from "34# is summarized inScheme 02[ The basic compound "34# can be prepared by several routes[ Thus\ similar to its Reanalogue "33#\ it forms by the action of NaðMn"CO#4Ł on "CO#2BrMn"h1!S1CPCy2# or the cationicspecies ð"CO#3Mn"h1!S1CPCy2#Ł¦ ð80OM273Ł[ Yields of about 79Ð89) are obtained when Mn1"CO#09

is re~uxed with S1CPCy2 or S1CP"Pri#2 in toluene or dichloromethane ð76CC361\ 80OM0572Ł[ Astepwise CO substitution of "34# by monodentate ligands or by the chelating ligand Ph1PCH1PPh1

generates the derivatives "35#Ð"37# ð76CC361\ 80OM0572Ł[ Reduction of "34# with LiðBHEt2Ł leads tothe intermediate lithium salt "38# which\ on alkylation\ can be transformed into the orange hydridocompounds "49# ð80OM2994Ł[

SPR1

3

(CO)3Mn Mn(CO)3

S(CO)3BrMn

S

SPR1

3

(CO)4MnS

SPR1

3

SPR1

3

(CO)3Mn Mn(CO)3

S SPR1

3

(CO)3Mn Mn(CO)3

SR2

SPR1

3

L(CO)2Mn Mn(CO)3

S

Scheme 13

+(45) R = Cy, Pri

S

Mn(CO)5Br

PR13

L(CO)2Mn

S2CPR13

Mn(CO)2L

S

Mn2(CO)10

NaMn(CO)5

S2CPR13

(49)

–

S

Li[HBEt3]

PR13

(CO)2Mn

R2X

Mn(CO)2

S

(50) R2 = Me, CH2Cl

P P

(46)

L

(47)

P P

L = P(OMe)3, P(OPh)3, P(OEt)3, PEt3, CNBut

(48) Cy = cyclohexyl

HH


"xvi# Compounds with the S1CPNi core

Two types of compounds with the S1CPNi core have been described[ Bianchini reported thestructure of the cationic brown complex "40#\ which has been obtained in 75) yield by reacting thenickel"9# complex NiN"CH1CH1PPh1#2 with MeSO2F in CS1 solution and crystallization with NaBH3

from acetoneÐether ð72JOM"135#C02\ 73JOM"169#140Ł[

S

S Ni

N

Ni PPh2

S

PR3

R3PSS

Ph2PPh2P

MeS

(52)(51)

The second type was prepared by Ibers and co!workers[ Thus\ addition of 1 equivalents of S1CPR2

to a solution of Ni"cod#1 in THF produced the compounds "41# "R�Me\ Et# containing two S1CPR2

units under head!to!tail dimerization of two CS1 molecules and movement of one PR2 molecule tothe nickel atom ð72IC300Ł[ The compound "41# with R�Me has also been obtained according toEquation "7# by reacting the nickel acyclic compound with CS1 in ether ð77OM1466Ł[

(52)

Ni

Me3PPMe3

+ CS2 (8)

"xvii# Compounds with the S1CPPt core

One type of compound with the S1CPPt core has been reported[ Thus\ S!alkyl "triphenyl!stannyl#dithioformates Ph2SnC"S#SR "R�Me\ CH1Ph\ allyl# react in benzene solution with oneequivalent of the Pt"9# complex "PPh2#1Pt"h!CH11CH1# to give the corresponding pale yellow "42#in quantitative yields as shown in Equation "8#[ The molecular structure of the methyl derivative isreported ð72IC2699Ł[

(9)S

PtSnPh3

RS

Pt

Ph3P

Ph3P

+ Ph3Sn

S

SR

Ph3P

Ph3P(53)

–C2H4

"xviii# Compounds with the S1CFe1 core

Various di}erent types of compounds have been described[ Seyferth reported the preparation of"43# in a two!step reaction starting from a dithioformate esterÐFe1"CO#5 complex which containsan acidic hydrogen atom[ Deprotonation with LDA followed by treatment with iodomethaneproduce orange "43^ R0�R1�Me# in 66) yield ð72OM0585Ł[ The starting lithiated species "havinga S1CLiFe core# rearranges to a salt!like product which on alkylation with R?X compounds can betransformed into "43#\ in which di}erent organic groups are located on sulfur as depicted in Scheme03[ The compounds can be viewed as complexes of Fe1"CO#5 with the six!electron sulfonium ylidedonor R1S1C1S ð76OM172Ł[

A related complex has been prepared by Busetto and co!workers[ The complex "44# with fouriron atoms\ in which the CS1 group functions as an eight!electron donor\ was prepared by reactingFpC"S#SFp "Fp�CpFe"CO#1# with excess Fe1"CO#8 in toluene[ Among others\ the dark greencompound "44# could be separated by column chromatography in 8) yield ð75G090Ł[

A series of compounds in which a carbene ligand C"SR#1 functions as a four!electron donorforming a S1CFe1 core has been described by Angelici and co!workers[ The cationic carbene complexðCp"CO#"MeCN#Fe1C"SR#1Ł¦ reacts in THF with ð"CO#2FeNOŁ− to give the violet compounds"46# in 39Ð64) yield[ The route outlined in Scheme 04 can also be extended to produce compounds


(CO)3Fe Fe(CO)3

SS(CO)3Fe Fe(CO)3

SR1S

R2

R1

LDA

(CO)3Fe Fe(CO)3

SS R1

Li

LDA

(CO)3Fe Fe(CO)3

SR1S

(54)

R2X

R1 = Me, EtR2 = Me, Et, allyl

Scheme 14

–

(CO)3Fe Fe(CO)3

SS

FeCp(CO)Cp(CO)Fe

O

(55) (56)

S SFe(CO)3

S(CO)3Fe Fe(CO)3

with the S1CFeCo and S1CRuCo core[ With PEt2\ the complex "46# containing the C"SMe#1 ligandis transformed into the black complex "47# "m[p[ 091Ð093>C# in 82) yield ð75IC1766Ł[ One 49!electron trinuclear complex with the S1CFe1 core is also described[ As depicted in the structure of"45#\ the carbene ligand of "46# can also serve as a m2!3!electron donor[ Compound "45# was one ofthe compounds obtained from irradiating a mixture of Fe"CO#4 with the trithiocarbonate complex"CO#4Cr0S1CS"CH1#1S in THF^ column chromatography yields black crystals "m[p[ 019>C# inabout 03) yield ð73JOM"151#58Ł[

Fe(CO)(NO)

SRS

R

O

OC

SR

SRMeCN

OC FeFe Fe(NO)(PEt3)

SRS

R

O

OC

Fe

S

S

S

S

SMe

SMe

+

(57)

[(Ph3P)2N][(CO)3FeNO]

=SR

SR

PEt3

(58)

Scheme 15

, ,

"xix# Compounds with the S1CFeCo core

The single type of compound with this core resembles compounds "46# and "47# in which the 02!electron fragment Fe"CO#NO is replaced by the isoelectronic fragment Co"CO#1 as depicted inScheme 05[ A solution of the appropriate cationic carbene complex ðCp"CO#"MeCN#Fe1C"SR#1Ł¦

in THF was combined with an equimolar solution of NaðCo"CO#3Ł[ Red to black solids "48# wereobtained in 59Ð69) yield by column chromatography on silica gel[ The compounds "48# can beconverted into the phosphine!substituted derivatives "59# in similar yields as reported for the iron


analogues by reacting with PEt2 in dichloromethane ð75IC1766Ł[ The chemistry of "48# has beendescribed ð73OM0927\ 74OM0115Ł[

Co(CO)2

SRS

R

O

OC

SR

SRMeCN

OC FeFe Co(CO)(PEt3)

SRS

R

O

OC

Fe

S

S

S

S

SMe

SMe

+

(59)

[(Ph3P)2N][Co(CO)4]

=SR

SR

PEt3

(60)

Scheme 16

, ,

"xx# Compounds with the S1CCoRu core

The compound Cp"CO#1Ru"m!C"SMe#1#Co"CO#1 "50# has been prepared analogously to "48# inScheme 05 but starting with the cationic carbene complex ðCp"CO#1"MeCN#Ru1C"SMe#1Ł¦^ redcrystals of "50# "m[p[ 009Ð001>C# are produced in 51) yield ð75IC1766Ł[

Co(CO)2

SMeS

Me

O

OC

Ru

(61)

5[00[1[0[2 Two seleniums or two telluriums and a group 04 element and:or a metalloid and:or a metalfunction

"i# Compounds with the Se1CSi1 core

Only one compound with this core has been described[ DuMont and co!workers reported theformation of the yellow triselenacyclopentane derivative "51# "m[p[ 048>C# in less than 4) yield byreacting a solution of "TMS#2CSeSeSeC"TMS#2 in dioxane with copper powder for 2 days at79Ð89>C^ the main product is "TMS#2CSeSeC"TMS#2 ð89CB1214Ł[

Se Se

SeTMS

TMS TMS

TMS

(62)

"ii# Compounds with the Se1CSiLi core

The compound "PhSe#1C"TMS#Li has been mentioned as being formed in situ by the consecutivereaction of "PhSe#1CH1 with LDA followed by treatment with TMS!Cl[ Further reactions withketones are described ð66CB741Ł[

"iii# Compounds with the Se1CPPd core

The redÐviolet to blueÐviolet compounds "52a#Ð"52c#\ containing two Se1CPPd centers\ form inabout 79) yield upon the reaction of "Ph2P#1Pd"h1!CSe1# with various methyl substituted


phosphine "PR2�PMe2\ PMe1Ph\ PMePh1# ligands as depicted in Equation "09#[ The compoundsshow decomposition points "DTA# of 040\ 048\ and 005>C\ respectively ð74ZN"B#0240Ł[ The structureof one derivative "PR2�PMe2# has been con_rmed by an x!ray di}raction study ð75JOM"200#52Ł[

SePd

Se

PdSe

PdSe

Se

SeR3P

R3P

PR3

R3P

R3P

PR3

PR3

(63) a; PR3 = PMe3b; PR3 = PMe2Phc; PR3 = PMePh2

(10)

5[00[1[1 Methanes Bearing Two Dissimilar Chalcogens

5[00[1[1[0 Oxygen\ sulfur and two functions derived from a group 04 element\ metalloid and:or ametal

"i# Compounds with the OSCN1 core

Compounds with this core are restricted to the species "53#Ð"55# and there is no common methodof preparation[ The spirocyclic compound "53# was obtained when the N!TMS ester of tri!thioisocyanuric acid was reacted with ethylene oxide in the presence of tetramethylethylammoniumbromide[ The compounds have been characterized by 0H NMR spectroscopy^ no further details ofpreparation are available ð52BAU0273Ł[ The compound "54# has been described ð64YGK025Ł[ Thecompound "55# "m[p[ 055Ð057>C# has been obtained in 80) yield by reacting 3!"2!methyl!thioureido#phenyl N!methoxycarbonyl!N!methylcarbamate with dimethyl sulfate in acetone ð64MI500!90Ł[ The radical "56# was reported to be formed upon x!ray irradiation of hydrous carnidazoleat 66 K^ addition of a radiogenic NO1 radical to the C1S bond was postulated ð81C029Ł[

N

N

N S

O

N

N

S

Me

S Me

MeCNN

H

N CN

SMe

O

HO

MeS

O

N

O

Me

O

OMe

N

H

N

H

MeMeS

MeOS(O)2O

NO2

N

NO2

S

OMe

(67)(66)

(64) (65)

H

"ii# Compounds with the OSCSi1 core

The preparation of the O!Si hemithioacetals "57# and "58# have been reported by Ricci et al[Thus\ treatment of "TMS#1CHSMe with n!buthyllithium in ether at −59>C followed by additionof bis"trimethylsilyl# peroxide "BTMSPO# for oxysilylation produced a 0 ] 0 mixture of unreactedstarting material and "57#[ Minor amounts of "58# were detected by GCÐMS analysis upon reacting"TMS#1CHSMe with mcpba in dry dichloromethane at −67>C ð75TL4874Ł[


MeS OR

TMS TMS

(68) R = TMS(69) R = OCOC6H4Cl-3

PhS OMe

TMS Li

(70)

"iii# Compounds with the OSCSiLi core

Lithiation of the O\S!acetal MeO"PhS#CHTMS with s!butyllithium in the presence of TMEDA at−67>C generates "69# ð75JOC768Ł[ A similar preparation with n!butyllithium in THF was describedð72SC874Ł[ The lithiated acetal has not been isolated and was used for the conversion of ketonesinto ketene!O\S!acetals[

5[00[1[1[1 Oxygen and selenium\ or oxygen and tellurium and two functions derived from a group 04element\ metalloid and:or a metal

Compounds with OSeC or OTeC fragments with adjacent group 04 elements\ metalloids ortransition metals have not yet been described[

5[00[1[1[2 Sulfur and selenium\ or sulfur and tellurium and two functions derived from a group 04element\ metalloid and:or a metal

"i# Compounds with the SSeCSiLi core

According to low!temperature 0H NMR studies\ the compound PhS"PhSe#CLiSiMe1Ph is presentin THF and also in THFÐHMPTA solution as a separated ion pair with diastereomeric TMS groupsup to −19>C[ At about 6>C in THFÐether\ the signals coalesce^ a rotation barrier around the C0Sbond was suggested ð82AG0378Ł[

"ii# Compounds with the SSeCPPd core

The only three compounds in this series are reported by Werner et al[ As with their S1 analoguesand in a manner related to Equation "09#\ various Pd"PR2#3 compounds "PR2�PMe2\ PMe1Ph\PMePh1# add CSSe in ether to give the dimeric red compounds "60a#Ð"60c# in about 74) yield asshown in Equation "00#[ From spectroscopic data the authors could not decide between the twopossible isomers involving a Se or a S bridge of the Pd0C bond ð74ZN"B#0240Ł[

(71) a; PR3 = PMe3b; PR3 = PMe2Phc; PR3 = PMePh2

S

PdS

PdSe

Se

R3P

PR3

PR3

R3P

Se

PdSe

PdS

S

R3P

PR3

PR3

R3P+ (11)CSSe

Pd(PR3)4

5[00[2 MONOCHALCOGENOMETHANES

The majority of compounds in this section contain a m2!CER carbyne ligand "E�chalcogen#bridging a triangular face of a transition metal cluster compound[ R can also be a 05! or 06!electrontransition metal fragment\ for example C4H4Fe"CO#1\ Mn"CO#4\ etc[ In this case the CE unit can beconsidered as m3!bridging[ Not included are cluster compounds in which only the 05!electron ligandCE coordinates at an appropriate trinuclear cluster in a m2!manner[ Many compounds in this seriesalso arise from the coordination of a E1CXY compound at a transition metal in an h1!manner[

The bonding of a CER fragment to main group elements is restricted to few examples bearingthe OCN2 core[ Thus\ no compounds with the ECSi2\ ECP2\ or related units have been described[

226Monochalco`enomethanes

The compounds are arranged in a manner such that the CER fragment "E�chalcogen# is bondedto three identical main group elements\ mixed main group elements\ mixed main and group transitionmetal elements\ three equal transition metal elements\ and di}erent transition metal elements[

5[00[2[0 Methanes Bearing One Oxygen Function and Three Functions Derived From the Group 04Element\ Metalloid and:or a Metal

5[00[2[0[0 Compounds with the OCN2 core

Two types of compounds with the OCN2 core have been described[ Kantlehner et al[ reportedthe preparation of the carbonic orthoamide derivatives "61a#Ð"61c# "R�Me\ Et\ Pri# which formupon addition of the corresponding alcohol!free NaOR to ðC"NMe1#2ŁCl in THF solution[ Fractionaldistillation produced "61a# "m[p[ 39Ð31>C#\ "61b# "b[p[ 59Ð64>C at 09 torr#\ and "61c# "b[p[ 28Ð39>Cat 9[0 torr# in 43)\ 28) and 53) yields\ respectively ð68LA1978Ł[ Compounds "61a# and "61b# havealso been obtained by treating C"NMe1#3 with an equimolar amount of the corresponding HOR asdepicted in Scheme 06 ð65JOM"094#C08Ł[

OR

Me2N

Me2N

Me2N NMe2

Me2N

Me2N

Me2NNMe2 Cl–

Me2N

Me2N

+NaOR HOR

(72) a; R = Meb; R = Etc; R = Pri

Scheme 17

Spirocyclic compounds in this series form as 2 ] 0 adducts of various alkyl isocyanides withaminoaziridines in acetonitrile "Scheme 07#[ The compounds "62a# "m[p[ 064Ð071>C# and "62b#"m[p[ 050Ð051>C# are formed in 82) and 53) yield\ respectively[ Protonation of "62a# with aqueousHCl results in the formation of the cationic compound "63# in 32) yield ð70LA153Ł[

N

N

NO

N

Ph

Me2N

R1 O

OR1

N

NMe2

PhN •

R1

O

R2

N

N

NO

NH

Ph

Et

Me2N

Me O

OMe

+

(74)

+

a; R1 = Me; R2 = Me

b; R1 = Et; R2 = H

HCl

Cl–

Scheme 18

3

(73)

R2

The spirocyclic compound "64# is probably formed as an intermediate similar to Scheme 4\ whenMe2SnNMeCH1CH1NMeSnMe2 is allowed to react with the appropriate ethylene thionocarbonate^the compound could not be isolated ð69MI 500!90Ł[

N

N

N

O

Me Me

Me

(75)

5[00[2[0[1 Compounds with the OCNSiTa core

Compounds with this core can formally be considered as adducts of pyridine derivatives at h1!bonded tantalum silaacyl compounds via the acyl carbon atom[ The starting unstable silaacyl


complex C4"Me#4Cl2Ta"h1!C"O#TMS# has been obtained by CO insertion into the Ta0Si bond ofC4"Me#4Cl2TaTMS[ The orange compounds "65# precipitate from pentane solution in about 89)yield upon addition of the appropriate pyridine derivative NR1 ""65a#\ NR1�pyridine\ m[p[84Ð87>C^ "65b#\ NR1�NC4H3Me!3^ "65c# NR1�NC4H2Me1!1\5# as follows from Scheme 08[ Donorexchange occurs in "65a# with the stronger base 3!methylpyridine to give "65b# and excess pyridine!d4 liberates 0 equiv[ of pyridine from "65a# with incorporation of the deuteriated donor ð78JA038Ł[

(77) (76)a; R = Meb; R = Etc; R = OMe

a; NR2 = NC5H5b; NR2 = NC5H4Me-pc; NR2 = NC5H3Me2-o,o

O(C5Me5)Cl3Ta

R2NTMS

O(C5Me5)Cl3Ta

Pr3PTMS

PR3 NR2

CO/NR2CO/PR3

O(C5Me5)Cl3Ta

TMS

(C5Me5)Cl3Ta-TMS

CO

PR3

Scheme 19

5[00[2[0[2 Compounds with the OCPSiTa core

Closely related to the compounds with the OCNSiTa core are those with the OCPSiTa core whichwere prepared in a manner analogous to the pyridine derivatives "65# as depicted in Scheme 08[Starting again with C4"Me#4Cl2TaTMS\ addition of PR2 under CO pressure "9[44 MPa^ 79 psi#produced the compounds "66# in about 74Ð89) yield as pale yellow powders[ However\ solutionsof "66# in benzene or diethyl ether are intensely colored ""66a#\ blue^ "66b#\ deep purple^ "66c#\ darkred# and decomposition occurs within a few hours[ PMe2 converts "65a# into "66a# in 89) yieldð78JA038Ł[ The structure of "66b# was established by an x!ray study ð78JA038\ 89AX1263Ł[

5[00[2[0[3 Compounds with the OCFe2 core

This section includes compounds in which the m2!bonded COR group bridges the face of atriangular cluster or one face of a tetrahedral cluster\ contributing three electrons to the number of37 or 59 CVE[ Not included are butter~y clusters with 51 CVE\ in which the carbon atom is bondedto four Fe atoms ð74JA7025\ 74JA7036Ł[

The neutral orangeÐred biscarbyne complexes "67# "a\ R�Me# can be prepared either by alky!lation of the anion ðFe2"CO#8"m2!MeCO#Ł− with excess MeSO2F in dichloromethane at elevatedtemperature in about 09) yield ð72CC0446Ł or in not speci_ed yield "b\ R�Et# by alkylation of theanion ðFe2"CO#8"m2!CMe#"m2!CO#Ł− with ðEt2OŁBF3 ð74OM0325Ł[ Replacement of CO in "67b# byPPh2 leads to "68# in about 84) yield[ Both compounds can also be generated from the cor!responding m2!h1 alkyne complexes as depicted in Scheme 19 ð74OM0325Ł[

The dark red ferrocenyl derivative "79# forms in 2) yield along with bisalkylidyne complexes"70a# and "70b#\ and "67a# by reacting ferrocenyllithium with Fe1"CO#8 in THF at room temperature^the compounds could be separated by column chromatography over silica gel ð89ZN"B#336Ł[

The bisalkylidyne complex "70a# in which two m2!COMe groups are symmetrically bonded to atrinuclear cluster was earlier prepared in about 04) yield by reduction of Fe2"CO#01 with n!butyllithium and subsequent treatment of the reaction mixture with ðMe2OŁBF3 or in a similarprocedure from HFe2"m1!COMe#"CO#09 in 11) yield using t!butyllithium ð77OM701Ł[

Anionic species with one m2!COR and one m2!CO function have also been isolated[ One routestarts with the trinuclear dianion ðFe2"CO#00#Ł1−\ which reacts with the electrophiles MeSO2F\EtSO2F and MeCOCl to produce the red compounds "71a#Ð"71c# "R�Me\ Et\ MeCO# obtained asthe ð"Ph2P#1NŁ salts in 62)\ 32) and 75) yield\ respectively ð68IC0125Ł[ A similar reaction using


(CO)3FeFe(CO)3

Fe(CO)3

OR

(CO)3FeFe(CO)3

Fe(CO)3

O

(CO)3Fe

OFe(CO)3

Fe(CO)3

––

Me+

(CO)3FeFe(CO)3

Fe(CO)2PPh3

OEt

Et+

Fe(CO)4(CO)3Fe

Fe(CO)3

OEt

(78) a; R = Meb; R = Et

Fe(CO)3PPh3(CO)3Fe

Fe(CO)3

CO

(79)OEt

–CO

TPPh3

PPh3

Scheme 20

(CO)3FeFe(CO)3

Fe(CO)3

OMe

OR

(CO)3FeFe(CO)3

Fe(CO)3

O

OR

(CO)3FeFe(CO)3

Fe(CO)3

(81) a; R = Meb; R = O(CH2)4OMe

–OMe

Fc

(82)(80) a; R = Meb; R = Etc; R = COMed; R = COCH=CHMee; R = COCH=CHPhf; R = CH2OMe

unsaturated acyl halides as electrophiles gave "71d# and "71e# in low yields ð78JOM"257#088Ł[ Theother route comprises the reaction of ðFe1"CO#7Ł1− with ClCH1OMe in THF to produce the red salt"71f# "R�CH1OMe#\ which was isolated in 11) yield as the NEt3 salt ð70CC078\ 70CC1385Ł[

The brown complex "72# with one Cp ring coordinated at one Fe atom of the trinuclear corehas only been obtained as a by!product during the formation of heterodinuclear and trinuclearcompounds[ The structure was con_rmed by an x!ray determination ð76OM708Ł[ The complex formsin 2[3) yield upon reacting HFe2"m!COMe#"CO#09 with "Ni"m!CO#"Cp1#1 ð75OM0092Ł or in about4) yield from "cyclooctene#1Fe"CO#2 and Cp"CO#Fe"m!CO#"m!COMe#Mn"CO#"h4!CH2C4H3#\ withthe main product being a complex with a OCFe1Mn core ð76JA1732Ł[

CpFeFe(CO)3

Fe(CO)3

OMe

(83)

O

O


The unstable hydrido complex "73# was mentioned as being formed from hydrogenation of thecluster HFe2"m!COMe#"CO#09^ however\ its stable dark purple SbPh2 derivative "74# can be isolatedin 11) yield if the reaction is carried out in the presence of excess of the ligand ð72OM108Ł[ Therelated complex "75# in which the three hydrogen atoms\ serving as one!electron donors\ arereplaced by the three!electron donor Bi atom is obtained in 54) yield by alkylation of the anionðBiFe2"CO#09Ł− with MeSO2CF2 in CH1Cl1 solution ð75IC1361Ł[

H

(CO)3Fe

Fe(CO)3

Fe(CO)3

OMe

H

H

H

(CO)3Fe

Fe(CO)2

Fe(CO)2

OMe

H

H

SbPh3

SbPh3

(CO)3Fe

Fe(CO)3

Fe(CO)3

OMe

Bi

(CO)3Fe

Fe(CO)3

Fe(CO)3

Pt

(84)

H

OMe

Ph3P CO

(85) (86) (87)

The trinuclear hydrido cluster HFe2"m!COMe#"CO#09 gave black crystals of the heteronucleartetrahedral cluster Fe2Pt"m2!H#"m2!COMe#"CO#09"PPh2# "76# in about 49) yield when it was allowedto react with Pt"C1H3#1PPh2 at room temperature in ether ð71CC40Ł[

The anionic tetranuclear black purple cluster ðFe3"m!CO#"m2!COMe#"CO#00Ł− "77# was obtainedby alkylation of the dianion ðFe3"CO#02Ł1− with either ðMe2OŁ¦ðBF3Ł− ð79CC679\ 79CC670Ł or MeSO2Fð79CC667\ 71JA4510Ł\ both in dichloromethane\ in about 44) yield^ the compound was isolated asthe ð"Ph2P#1NŁ salt[

(CO)2Fe

Fe(CO)3

Fe(CO)3

Fe(CO)3

(88)

O

OMe

–

5[00[2[0[4 Compounds with the OCCo2 core

This section contains two types of compounds with this core[ A few derivatives of the trinuclearcluster Cp2Co2"m2!COR#1 are known\ whereas the majority of compounds are based on the trinuclearcluster Co2"CO#8"m2!COR#\ in which R represents various organic substituents including main groupor transition metal elements[ Starting material for the second series is mainly Co1"CO#7 or thecovalent trinuclear cluster Co2"CO#8"m2!COLi#[

Thus\ the reaction of Co1"CO#7 with the trialkylborane adducts R2NBH2 produces the blackcompounds "78a# and "78b# in moderate yields ð57IC1154Ł[ A similar treatment of Co1"CO#7 in THFwith the adducts Et2NBX2 "X�Cl\ Br# gives "78c# and "78d# ð61JOM"35#038\ 64JOM"091#098\ 65ZN"B#231Ł[Co1"CO#7 is also the starting material for the preparation of the red siloxy compound "89c#\ whichcan be obtained in 43) yield by reacting with 0!hydrosilatrane in THF ð82IC4772Ł\ whereas redÐblack "89a# "m[p[ 097>C dec[# and "89b# "m[p[ 80Ð82>C# have been obtained by the reaction of"CO#8Co2"m2!COLi# with the corresponding ClSiR2 in diethyl ether in 33) and 19) yield\ respec!tively ð69JOM"13#C50Ł[

Various compounds with Ti\ Zr or Hf ""80#Ð"82## in the apical position have also been prepared[Thus\ one equivalent of "CO#8Co2"m2!COLi# reacts with Cp1MCl1 "M�Ti\ Zr\ Hf# in toluene toproduce the deep red to black colored cluster compounds "80# "a\ m[p[ 023>C\ 46) yield^ b\ m[p[027Ð030>C\ 61) yield^ c\ m[p[ 028Ð031>C\ 77) yield#[ Two equivalents of "CO#8Co2"m2!COLi# ina similar procedure leads to the disubstituted compounds "81# "a\ m[p[ 047Ð059>C\ 28) yield^ b\m[p[ 034>C\ 24) yield^ c\ m[p[ 034>C\ 54) yield#[ Treatment of "80# with solid NaOH in tolueneresults in the formation of the oxo!bridged derivatives "82# "a\ m[p[ 054>C\ 25) yield^ b\ m[p[ 059Ð053>C\ 04) yield^ c\ m[p[ 045Ð059>C\ 08) yield# ð67CB0592Ł[ Compound "80a# can also be obtainedfrom Co1"CO#7 and Cp1TiCl1 ð65JOM"002#56Ł[ Black crystals of "83# are formed in 12) yield fromNaðCo"CO#3Ł and CpTiCl2 in toluene ð67CB0128Ł[ The chromium!substituted complex "84#\ which


is extremely sensitive to atmospheric oxygen and moisture\ forms in about 59) yield by treatmentof Co1"CO#7 with Cp1Cr1"m!OCMe2#1 ð89JOM"273#168Ł\ while the red complex "85# is the product ofthe reaction of Co1"CO#7 with one equivalent of pyridine in similar yield ð76AG570Ł[ All the maingroup and transition metal!substituted compounds are summarized in Scheme 10[

(CO)3CoCo(CO)3

Co(CO)3

[Co]3 OLi

O OTi

Cp Co(CO)4

[Co]3 [Co]3

CrCp

But

But

O

CpCr

[Co]3

CoO O

pypy

py py

[Co]3

[Co]3

OBX2NR3

[Co]3

OSiR3

[Co]3

OMCpCl

[Co]3

O O

Cp2M

[Co]3 [Co]3

(95)(94) (96)

O

Cp2M

[Co]3

Cp2Cr2(OBut)2

LiCo(CO)4

CpTiCl3

R3NBX3

O

Cp2M

O

[Co]3

(90)

py

R3SiCl

(89)

Co2(CO)8

[Co]3 OLi(91)

HSi(C2H4)3NCp2MCl2 a; R = Me, X = Hb; R = Et, X = H c; R = Et, X = Cld; R = Et, X = Br

[Co]3 O =

(92)

a; SiR3 = SiMe3b; SiR3 = SiPh3c; SiR3 = Si(C2H4)3N

O

NaOH

(93)(91)–(93) a; M = Ti

b; M = Zrc; M = Hf

Scheme 21

The starting material for many compounds in Scheme 10\ black crystals of "CO#8Co2"m2!COLi#\have been obtained from LiCo"CO#3 and Co3"CO#01 or Co1"CO#7 in ether as Et1O ð68CC285Ł orPri

1O adducts ð79AG300Ł[ The compound can be freed from ether upon reacting with Ph1O ð70AG83Ł[Addition of dry HCl in hexane gives red crystals of the corresponding acid "CO#8Co2"m2!COH# "86#\which rapidly decomposes at room temperature ð68CC286Ł^ the acid can be stored under CO or Arat liquid!nitrogen temperature ð70AG83Ł[ With NEt2 the dark violet adduct "CO#8Co2"m2!COH =NEt2# is obtained ð70AG104Ł[ Acetylation of "CO#8Co2"m2!COLi# with MeCOBr in benzeneat room temperature gives "CO#8Co2"m2!COCOMe ""87#\ m[p[ 012>C# in 56) yield ð65CB2228Ł[ Thealkyl derivatives "88# have been obtained by di}erent routes[ The red!black methyl derivative"88a# can be obtained from Co1"CO#7 either by reacting with MeOCHCl1 in THF in 16) yieldð62JOM"49#154Ł or by reacting with Fe2"H#"m!COMe#"CO#09 in 37) yield ð76OM708Ł[ The consecutiveaddition of LiPh:ether at −59>C and Et2OBF3 in CH1Cl1 at −09>C to a solution of Co1"CO#7 doesnot form a Fischer!type carbene complex but leads to the formation of "88b# "the ethyl derivative#in about 3) yield ð72M740Ł[ The organic species are shown in Scheme 11[

The second type of compound with the Co2CO core comprises two species and has been reportedby the group of Floriani[ The compounds originate from trimerization of a CpCo fragment which


[Co]3 OLiLiCo(CO)4

HCl

i, LiPhii, Et3OBF4

O

[Co]3

(98)

O

OEt

[Co]3

(99b)

Co2(CO)8

OH

[Co]3

(97)

OMe

[Co]3

(99a)

MeCOBr MeOCHCl2

(CO)3CoCo(CO)3

Co(CO)3

[Co]3 O =

O

Scheme 22

forms from CpCo"CH11CH1#1 upon losing the labile bonded ethylene molecules[ Thus\ blackcrystals of "099# crystallized in 37) yield from a toluene solution when the ethylene complex wasallowed to react with Cp1Ti"CO#1^ in contrast to the other m2!COTi species discussed above withTi"IV#\ the titanium atom has the oxidation number 2[ Reaction of "099# with excess TMS!Cl inTHF replaces both Cp1Ti fragments by TMS groups with formation of red!violet "090# in about45) yield ð75AG172\ 77NJC510Ł[ The formation of the compounds is depicted in Scheme 12[

CpCo

CoCp

CoCp

O-TMS

O-TMS

CpCo

CoCp

CoCp

OTiCp2

OTiCp2

(100) (101)

TMS-ClCp2Ti(CO)2 + CpCo(CH2=CH2)2 – CH2=CH2

Scheme 23

5[00[2[0[5 Compounds with the OCW2 core

The only compound with this core\ W3"OCH1Pri#01"CO#2 "091#\ has a structure equivalent to a{{spiked triangle[|| The dark green compound forms in ½49) yield when CO is added to a hexanesolution of the butter~y cluster W3"OCH1Pri#01 for 13 h^ _ve bridging OR groups "R�CH1Pri#stabilize the W0W bonds and the two CO groups are cis at one basal W atom ð78JA6172\89JOM"283#154Ł[

W

W(CO)2(RO)2W

RO

OR

OR

OW(OR)3

RO OR

OR

OR

(102)


5[00[2[0[6 Compounds with the OCRu2 core

Compounds with this core comprise homometallic and heterometallic species\ both with the samem2!COMe ligand[ The homometallic compounds are collected in Scheme 13[

The Ru analog H2Ru2"m2!COMe#"CO#8 "092# of the Fe cluster "73# has been obtained as brightorange crystals in 82) yield upon heating the trinuclear precursor HRu2"m!COMe#"CO#09 in hexanein the presence of H1 ð74JOM"176#246Ł[ Replacement of three CO groups in the basal plane by thetripod ligand MeC"CH1PPh1#2 gives the yellow "093# in about 49) yield with a face!capped structure[The introduction of the smaller tridentate ligand HC"PPh1#2 under the same conditions gives orange"094#\ in which the ligand behaves as a bidentate bridge spanning two equatorial sites on two Ruatoms ð80OM1273Ł[ PPh2 replaces one or two CO groups to give "095# and "096# in 29) and 03)yield\ respectively ð78OM0169Ł[ 0\2!Cyclohexadiene behaves as a 3!electron donor to one Ru atomand replaces one CO and H1 and reacts in the presence of diethyl fumarate to give "097# in low yieldð72OM0068Ł[ Deprotonation of "092# with K!Selectride:THF gives the anion "098#\ which can beisolated as the ð"Ph2P#1NŁ salt ð78OM0169Ł[

Ru(CO)3

Ru(CO)2PPh3(CO)3Ru

H

H

H

(106)

OMe

Ru(CO)2PPh3

Ru(CO)2PPh3(CO)3Ru

H

H

H

(107)

OMe

+

PPh3

Ru(CO)3

Ru(CO)3(CO)3Ru

H

H

H

(103)

OMe

Ru(CO)3

Ru(CO)3(CO)3Ru

H

H

(109)

OMe

K

–

Ru(CO)3

Ru(CO)2

(CO)3Ru

(108)

OMe

H Ru(CO)2

(CO)3Ru

H

H

H

OMe

PPh2Ph2PPPh2

(104)

Ru

Ru(CO)2

(CO)3Ru

H

H

H

(105)

OMe

PPh2

PPh2

(CO)2PPh2

Ru(CO)4

Ru(CO)3(CO)3Ru

H

OMe

H2

(Ph2PCH2)3CMe

(Ph2P)3CH

Scheme 24

Ru(CO)2

A series of heterometallic compounds are summarized in Scheme 14[ Some compounds are derivedfrom a homometallic trinuclear species by replacement of one or more bridging H atoms by theisolable AuPR2 group or a similar one!electron donating group[ Thus\ treatment of the basiccompound "092# with AuMePPh2 under mild conditions produces three orange compounds in whichone "000#\ two "001#\ or all "002# bridging H atoms of "092# are replaced by the AuPPh2 unitð71CC662\ 72JCS"D#1488\ 72JOM"138#162\ 78OM0169Ł[ A similar reaction starting from the anion "098# andthe corresponding ClMPPh2 produces "000# "M�Au#\ "003# "M�Ag# and "004# "M�Cu# in about54Ð64) yield^ these compounds can be converted into "005#Ð"007# by treating with PPh2 in re~uxingCH1Cl1 in yields greater than 89) ð78OM0169Ł[ The anion "098# reacts with ðRh"CO#2"PPh2#1Ł− inmethanol at −19>C to form the red air!stable tetranuclear complex "008# in 79) yield ð78CC0918Ł[


Ru(CO)3

Ru(CO)3(CO)3Ru

H

H

MPPh3

OMe

Ru(CO)3

Ru(CO)3(CO)3Ru

H

H

OMe

Ru(CO)3

Ru(CO)3(CO)3Ru H

OMe

Ph3PAuAuPPh3

Ru

RuRu

OMe

AuAu

Au

Ru(CO)3

Ru(CO)2PPh3(CO)3Ru

H

H

MPPh3

(109)

–

(111), (114), (115)

ClMPPh3

OMe

AuMePPh3 (103) (111) +

(113)

Ru(CO)3

Ru(CO)3(CO)3Ru

H

Rh(CO)2PPh3

(116), (117), (118)

+PPh3(111), (116)(114), (117)(115), (118)

OMe

; M = Au; M = Ag; M = Cu

Ru = Ru(CO)3Au = AuPPh3Scheme 25

H

(119)

[Rh(CO)3(PPh3)2]–

AuMePPh3

(112)

The red compound "019# with three transition metals is obtained in about 4) yield by reducing thetetrahedral cluster Ru2RhH1"CO#09"PPh2#"m!COMe# in THF with KðBHBu2Ł followed by addition ofsolid Au"PPh2#Cl in dichloromethane at −89>C ð80JCS"D#0906Ł^ the reaction is depicted in Equation"01#[

Ru(CO)3

Ru(CO)2(CO)3Ru

H

H

(CO)2Rh

PPh3

Ru(CO)2

Ru(CO)3(CO)3Ru

AuPPh3

Rh

O

MeO PPh3

(120)

(12)

(CO)2K[BHBu3]

Au(PPh3)Cl

The only compound with a m2!CORu ligand spanning a Ru2 plane is described by Geo}roy andco!workers[ The complex "010# forms either in about 4) yield by reacting the cluster Ru2"CO#8"m2!CO#"m2!NPh# with diphenylacetylene or in 38) by reacting the starting cluster with one of theother reaction products\ a metallapyrrolidone complex as depicted in Scheme 15 ð75OM1450Ł[

5[00[2[0[7 Compounds with the OCOs2 core

Closely related to the iron cluster "73# and its ruthenium derivative "092# is the correspondingosmium compound "011#[ It is similarly obtained in about 82) yield by heating HOs2"m!COMe#"CO#09 with H1 in hexane for 1 h ð72OM108Ł^ as depicted in Equation "02#\ the reaction is reversibleand carbonylation regenerates the starting complex ð74JOM"176#246Ł[


Ru(CO)3

Ru(CO)3

(CO)3Ru

N

Ph

O

(CO)3RuN

PhPh

O

Ru(CO)3Ph

(CO)3RuN

Ph

O

Ru(CO)2

Ph

Ru(CO)3

Ru(CO)3Ru

N

Ph

O

PhC2Ph

PhC2Ph

(121)

Scheme 26

Os(CO)3

Os(CO)3(CO)3Os

H

H

H

(122)

OMe

Os(CO)4

Os(CO)3(CO)3Os

H

OMe

(13)CO

H2

The related compound "012# with a boroxine center could be isolated as a pale yellow precipitateupon hydroboration of "m!H#1Os2"CO#09 by THF =BH2 in dichloromethane solution\ and the struc!ture was con_rmed by an x!ray structure determination ð73CC281Ł[

Os(CO)3

Os(CO)3(CO)3Os

H

H

H

(123)

O

OCOs3 =

B

OB

O

BOOs3CO OCOs3

OCOs3

A series of compounds with two bridging carbyne ligands have been described by Shapley andco!workers as shown in Scheme 16[ Thus\ sequential addition of phenyllithium and MeSO2CF2 ina Fischer!type manner to an ethereal solution of HOs2"m!COMe#"CO#09 at 9>C produces orangeÐred air!stable crystals of "013# "m[p[ 026Ð028>C# in 30) yield[ Protonation with HSO2CF2 retainsthe framework and gives the anionic complex "014#^ the proton bridges one Os0Os bond[ COsubstitution with excess of PPh2 gives a mixture of the orangeÐred compounds "015# "19) yield#and "016# "43) yield#\ which could be separated by TLC techniques ð75OM0646Ł[ Treatment of"013# sequentially with phenyllithium and MeSO2CF2 provided red crystals of the Fischer!typecarbene complex "017# in 55) yield^ the structure was con_rmed by an x!ray analysisð78JOM"260#146Ł[

Small amounts "09)# of the cluster "018# "Os5"CO#06"py#1# were formed\ when Os5"CO#07

was treated with excess pyridine "py# in dichloromethane^ the major product was thedianion ðOs4"CO#04Ł1−^ the yield can be enhanced to 19) by addition of Me2NO to the reactionmixture[ An x!ray analysis con_rmed the structure with one osmium atom in a {{spike|| arrangementð73CC0978Ł[


(CO)3Os

Os(CO)3

Os(CO)2PPh3

OMe

Ph

(CO)3Os

Os(CO)3

Os(CO)3

OMe

Ph

H

(CO)3Os

Os(CO)3

Os(CO)3

OMe

Ph

(CO)3Os

Os(CO)4

Os(CO)3

OMe

H

Ph3P(CO)2Os

Os(CO)3

Os(CO)2PPh3

(125)

OMe

Ph

(126)OH–

+

(CO)3Os

Os(CO)3

Os(CO)2

H+

OMe

Ph

PPh3

(124)

2 PPh3

i, PhLiii, MeSO3CF3

(127) (128)

Ph

OMe

Scheme 27

Ph–/Me+

(CO)3Os

Os(CO)2

Os(CO)3

O

(CO)3Os

(129)

Os(CO)2(py)2

Os(CO)3

py = pyridine

5[00[2[0[8 Compounds with the OCFe1Ni core

Only one compound with this core has been described[ BlueÐgreen crystals of Fe1Ni"m2!COMe#"m2CO#"Cp# "029# were obtained in 34) yield when HFe2"m!COMe#"CO#09 was allowed to reactwith "Ni"CO#Cp#1 in toluene on heating in a Carius tube[ The compound was separated bychromatography and the structure was con_rmed by an x!ray analysis ð75OM0092Ł[

(CO)3Fe

Ni

Fe(CO)3

OMe

O

(CO)3Fe

M

Fe(CO)3

OMe

O

(130)

H

(131) a; M = Cob; M = Rh

5[00[2[0[09 Compounds with the OCFe1Co core

The related complex "020a^ M�Co# is derived from "029# by replacement of the Ni atom by theisoelectronic CoH unit[ The greenÐbrown complex in which the hydrogen atom bridges the Fe0Fe


bond has similarly been obtained in 46) yield by reacting HFe2"m!COMe#"CO#09 with Co"CO#1Cp[Reaction of "020a# with MeAuPPh2 leads to the replacement of hydrogen by AuPPh2 with result ofblack crystals of "021# in about 52) yield ð75OM0092Ł[ As shown by the same group\ HgPh1 intoluene at 89>C similarly produces "022a^ M�Co# as the sole product ð76CC036Ł[

(132)

(CO)3Fe

M

Fe(CO)3

OMe

O

(133) a; M = Cob; M = Rh

(CO)3Fe

Co

Fe(CO)3

OMe

O

Ph3PAu(CO)3Fe

Hg

Fe(CO)3

OMe

O

M

5[00[2[0[00 Compounds with the OCFe1Rh core

The preparation of "020b^ M�Rh# is carried out in a manner similar to its cobalt derivativeby reacting HFe2"m!COMe#"CO#09 with Rh"CO#1Cp^ black crystals are obtained in 54) yieldð75JOM"209#56Ł[ The analogous reaction with HgPh1 leads to "022b^ M�Rh#^ however\ the solid!state structure shows bridging of the mercury atom the Fe0Rh bonds[ In solution a polytopalrearrangement takes place with the mercury atom migrating around the Fe1Rh triangle ð76CC036Ł[

5[00[2[0[01 Compounds with the OCFe1Mn core

The heterotrinuclear cluster "023# has been prepared in 79) yield from "cyclooctene#1Fe"CO#2and Cp"CO#Fe"m!CO#"m!COMe#Mn"CO#"h4!MeC4H3#^ a minor product is a similar complex with aOCFe2 core ð76JA1732Ł[ As depicted in Scheme 17\ addition of excess diazomethane ð76JA1732Ł ordiazoethane ð77OM683Ł to "023# stereospeci_cally yields the m2!methoxycarbyne\ m1!alkylidene cluster"024# in 04) "a\ R�H# or 51) "b\ R�Me# yield\ respectively[ The ethylidene cluster "024b^R�Me# decomposes at room temperature within 7Ð09 days to give small amounts of the isomer"024c# by ethylidene {{rotation[|| Further decomposition products comprise other dinuclear andtrinuclear species ð77OM683Ł[

(134)

CpFe

MnCpMe

Fe(CO)3

OMe

O

O

OCp(CO)Fe Mn(CO)CpMe

OMe

O

a; R = Hb; R = Me

(135)

(C8H14)2Fe(CO)3

Scheme 28

CHRN2

CpFe

MnCpMe

Fe(CO)3

OMeO

OCpFe

MnCpMe

Fe(CO)3

OMeO

O

R

(135c)

8 d


5[00[2[0[02 Compounds with the OCRu1W core

The tetranuclear species "025# "a\ R�H^ b\ R�Me#\ in which the m!COMe group bridges oneheteronuclear face of the tetrahedral cluster have been prepared by heating a mixture of Ru2"CO#09"m!COMe#H and the corresponding hydrido complex Cp?W"CO#2H "Cp?�C4H4\ C4Me4# in toluenefor 0 h ð89JCS"D#2922Ł[ The same group reported a similar reaction with CpW"CO#2C2CPh\ whichleads to "026# ð80OM1374Ł[

(CO)3Ru

Ru(CO)2

W(CO)Cp

OMe

Ru(CO)2

Ph

O

(CO)3Ru

Ru(CO)3

W(CO)2C5R5

OMe

Ru(CO)3

(136) (137)

5[00[2[0[03 Compounds with the OCW1Ru core

With one equivalent of CpW"CO#2H the tetranuclear complex "026# is converted into the penta!nuclear complex "027# in which the COMe group bridges a W1Ru face in a m2!manner[ The reactionhas been performed in re~uxing toluene to give red crystals in 13) yield ð80OM1374Ł[

Ru

W

W

OMe

Ru

(138)

CO

Ph

ORu

CO

Ru = Ru(CO)2W = WCp

5[00[2[1 Methanes Bearing One Sulfur Function and Three Functions Derived from the Group 04Element\ Metalloid and:or a Metal

The compounds in which two or three di}erent elements are attached to the SC carbon atom arerepresented by only a few examples[ Main group compounds consist with few exceptions of specieswith the SC"TMS#2 fragment[ The majority of samples in this section\ however\ are based on Co2

cluster compounds with a m2!C1S ligand or similar clusters in which one or two Co atoms arereplaced by other transition metals^ addition of an electrophile at the C1S sulfur atom gives a m2!methylidine ligand which contributes three electrons to the cluster[

5[00[2[1[0 Compounds with the SCN2 core

A series of compounds of the general type RSC"NO1#2\ in which the NO1 groups are bound tothe carbon atom via the nitrogen atoms\ have been described by a Russian group[ The compoundshave been obtained by the reaction of KC"NO1#2 with the appropriate RSCl in dimethoxyethane orether at about 9>C[ Recrystallization from chloroformÐhexane produced 1\3!"NO1#1C5H2SC"NO1#2"m[p[ 57Ð58>C# in 49) yield and PhSC"NO#2 "m[p[ 01Ð02>C# in 82) yield\ respectively ð62IZV249Ł[MeSC"NO1#2 was similarly obtained in 82) yield but puri_ed by distillation "b[p[ 39>C at0 mm Hg# ð62IZV249\ 64IZV0558Ł[ The compounds 3!"NO1#C5H3SC"NO1#2 "m[p[ 014Ð016>C# and 3!MeOC5H3SC"NO1#2 "m[p[ 25Ð28>C# have been prepared in the same manner in dichloromethane


solution in 76) and 69) yield\ respectively ð63IZV0249Ł[ PhSC"NO1#2 is also produced in 19) yieldby the reaction of K"C"NO1#2 with ðPhSŁðBF3Ł ð64IZV0558Ł[ Reactions with hydrogen halides havebeen described ð78IZV1095Ł[

5[00[2[1[1 Compounds with the SCSi2 core

The key compound for this series is HC"TMS#2\ which can be converted into HSC"TMS#2 "028#in 35) yield by treatment with MeLi and then with elemental sulfur after extractive puri_cationwith methanolÐKOH followed by sublimation ð74TL0980\ 74TL1148Ł[ A similar procedure with HC"Si!Me1Ph#2 generates pale yellow crystals of HSC"SiMe1Ph#2 "039# in 09) yield\ melting at 190Ð192>Cð76IC0377Ł[ DuMont and others obtained several sulfur!rich species using HC"TMS#2 or HSC"TMS#2as starting materials as shown in Scheme 18[ Thus\ treatment of "028# with SCl1 gives yellow "030#in 34) yield[ This compound is also produced along with "031# by oxidation of "028# with airð74TL0980\ 82CB0244Ł[ Desulfurization of the tetrasulfane "031# to "030# can be performed withelemental mercury[ The corresponding disulfane "032# forms as a mixture with the methyl derivative"033# ð82CB0244Ł[ The latter can also be obtained from "TMS#2CLi and Me1S ð89JOM"287#54Ł[ Startingwith a lithiated 1!ðð"trimethylsilyl#methylŁthioŁtetrahydropyran and TMS!Cl the compound "034#was prepared in 72) yield ð74JA5618Ł "Equation "03##[

SS

SS TMS

TMSTMS

TMSTMS

TMS

(142)

SS

TMS

TMSTMS

(141)

TMS

TMSTMS

Hg

(143)

SMe

TMS

TMS

TMS

(144)

SH

TMS

TMS

TMS

(139)

TMS

TMS

TMS

MeLi/S8/H+

SCl2

O2

Me/LiBr2

+

Scheme 29

SS

S TMSTMS

TMSTMS

TMSTMS

O S TMS

i, BuLi

ii, TMS-Cl

(145)

O S TMS

TMSTMS (14)

Several S!metalated derivatives have been prepared by the groups of Power and Lappert and thecompounds are summarized in Scheme 29^ starting materials are the hydrogen compounds "028#and "039# or the corresponding lithium salts[ The pale yellow trimeric and tetrameric silver com!pounds "035# "55) yield# and "036# "81) yield\ m[p[ 124>C# are the result of the reaction with NEt2and AgNO2 in re~uxing benzene or acetonitrile\ respectively^ the compounds contain six! and eight!membered AgS rings ð76IC0377Ł[ A similar tetrameric gold compound "037# has been prepared in58) yield from the lithium compound and AuCl\ whereas Ph2PAuCl produces the monomericcompound "038# "m[p[ 193Ð196>C# as colorless crystals in 58) yield ð82IC4015Ł[ The reaction of"028# with MðN"TMS#1Ł1 compounds "M�Sn\ Pb# produces various dimeric or polymeric species"049#Ð"041# containing the SCSi2 core^ the polymeric lithium salt was obtained with butyllithium inhexane ð74CC0665Ł[ The lithium salt LiSC"TMS#2 = 2[4THF was reported to be a dimer with a squareLi1S1 core and was prepared in the presence of small amounts of THF ð74CC0563Ł[


SAuPPh3

TMS

TMS

TMS SAu

TMS

TMS

TMSSLi

TMS

TMS

TMS

SH

RMe2Si

RMe2Si

RMe2Si SAg

RMe2Si

RMe2Si

RMe2Si

SPb

SPb

TMS TMSTMS

TMS TMSTMS

SS TMS

TMSTMS

TMS

TMSTMS

(149)

SPb

SPb

TMS TMSTMS

TMS TMSTMS

NR2R2N

(148)

AuClAuClPPh3

Li

(139)(140)

AgNO3

S

Sn

S

TMS

TMS

TMS

TMS

TMS

TMS

(151)(150)

Pb(NMe2)2

4R = MeR = Ph

R = MeR = Ph

(146)(147)

M[N(TMS)2]2M = Sn, Pb

4

(152)

Scheme 30

n

5[00[2[1[2 Compounds with the SCSi1P core

Two di}erent compounds with this core have been described[ The reaction of MesP1C"TMS#1"Mes�mesityl# with 0

3S7 leads to an inseparable mixture of MesP"S#1C"TMS#1 and the thiaphos!

phirane MesP"1S#"m!S#C"TMS#1 "042#[ The mixture is completely converted into "042# by additionof a second equivalent of sulfur "Scheme 20# ð73CC587Ł[ An additional compound with the SCSi1Pcore\ "043#\ has been described as very water sensitive and has been prepared by reacting "EtO#1P"O#CSMe"TMS#Li with TMS!Cl in THF at −67>C ð78S090Ł[

mes P

S

P

TMS

TMS

mes

mes P

STMS

TMS

TMS

TMS

(153)

S8

1/8 S8

1/4 S8

Scheme 31

P

O

EtOEtO

TMS

TMSTMS

(154)


5[00[2[1[3 Compounds with the SCPSiLi core

"EtO#1P"O#CSMe"TMS#Li results from lithiation of "EtO#1P"O#CHSMe"TMS# with BunLi inTHF at −67>C and was not isolated[ The species reacts with ketones and aldehydes and can beused to transfer the "EtO#1P"O#CSMe"TMS# fragment to various substrates ð78S090Ł[

5[00[2[1[4 Compounds with the SCSi1Li core

PhSCLi"TMS#1 "044^ R�Ph# is obtained in situ by dropwise addition of butyllithium in hexaneto PhSCH"TMS#1 in THF at −67>C[ This and similar lithium compounds have been formulatedas ionic species and have been used to replace the oxygen atom of various epoxides by the carbenePhS"TMS#C to give cyclopropanes ð78TL6922Ł[ The methyl derivative has been obtained similarlyin 099) yield ð66CB741Ł[

TMS TMS

RS Li

(155)

5[00[2[1[5 Compounds with the SCN1Fe core

The reaction of Fe1"CO#8 with tetramethylthiourea in ether for 13 h followed by chromatographyin Fluorosil leads to Fe1"CO#5"SC"NMe1#1# "045# in 1[5) yield along with Fe2"CO#8S1 "9[0)# and"Me1N#1C1S0Fe"CO#3 "5[1)# "Equation "04## ð63IC114Ł[

Fe2(CO)9 + (Me2N)2CS Fe3(CO)9S2 + (CO)4FeS

NMe2

NMe2

+ S

Fe(CO)3(CO)3Fe

N

NMe2Me

Me

(156)

(15)

5[00[2[1[6 Compounds with the SCNSnPt core

Compounds of the general type "PPh2#1Pt"SCSnPh2NR1# "046^ NR1�NMeH\ N"CH1#3# areprepared by the reaction of the corresponding Ph2SnC"S#NR1 with "PPh2#1PtC1H3 in benzene for13 h[ The pale yellow products were precipitated with hexane and recrystallized from benzeneÐhexane[ The yields were approximately 49)^ by!products are the corresponding Sn!bonded species"PPh2#1PhPtSn"Ph#1C"S#NR1 "Equation "05## ð72IC2699Ł[ The compounds can also be considered interms of an h1!coordination of S1C"SnPh2#NR1 at the Pt fragment[

SPt

Ph3P

Ph3PPh3Sn

NR2

PtPh3P

Ph3P+ Ph3Sn

S

NR2

(157)

–C2H4

NR2 = NMeH, N

(16)

5[00[2[1[7 Compounds with the SCSiSnLi core

The compounds RSCLi"TMS#"SnMe2# "047^ R�Me\ Ph# have been obtained in 099) yield bylithiation of the corresponding RSCH"TMS#"SnMe2# with LDA in THFÐHMPTA ð66CB741Ł[

Me3Sn Li

RS TMS

(158)


5[00[2[1[8 Compounds with the SCFe2 core

Only one compound of this type has been described[ The tetranuclear compound Fe3"CO#00"CS#S"048# was obtained as one of the products from the reaction of Fe2"CO#01 with CS1 in hexanesolution at 79>C under 09 atm COÐAr pressure[ Both the compounds in Equation "06# have beenformed in about 3) yield ð79CC701Ł[

(CO)3Fe

Fe(CO)2

Fe(CO)3

S

S

(159)

Fe(CO)3

Fe3(CO)12 + CS2 + Fe3(CO)9S2 (17)

5[00[2[1[09 Compounds with the SCCo2 core

The compounds with this core are derived from Co2Cp2"m2!CS#"m2!S# and the hypothetical clusteranion ðCo2"CO#8"m2!CS#Ł−^ both are electron precise cluster compounds[ Of the two sulfur atoms ofthe _rst species\ only that at the m2!C1S ligand is nucleophilic enough to react with a variety ofelectrophilic reagents Y to produce compounds of the general type Co2Cp2"m2!CSY#"m2!S#^ thecorresponding Co2"CO#8"m2!CSY# compounds are formed in a complex reaction from Co1"CO#7[The electrophile Y can be a cationic group R¦ or a 05!electron transition metal Lewis acid as shownin Scheme 21[

Starting from Co2Cp2"m2!CS#"m2!S#\ the alkylating agents RI "R�Me\ Et\ Pri# produce the blacksalts ðCo2Cp2"m2!CSR#"m2!S#ŁI "059aÐc# from a THF solution in about quantative yields[ The reactionwith PriI has only been conducted in an NMR tube[ A decreasing reactivity order MeI×EtI×PriIwas found\ indicated by an increasing reaction time in the order 0 h\ 4 h\ 4 days\ respectively[ Blackcrystals of Co2Cp2"m2!CSCr"CO#4#"m2!S# "050# have been obtained in 24) yield by treating a freshlyprepared THF solution of "CO#4CrTHF with Co2Cp2"m2!CS#"m2!S#^ the complex could be puri_edby recrystallization from THFÐhexane ð68AG552\ 79CB0543Ł[

CpCo

CoCp

CoCp

S

S(160)

R

CpCo

CoCp

CoCp

S

S

(161)

Cr(CO)5

(CO)5CrTHF RICpCo

CoCp

CoCp

S

Sa; R = Meb; R = Etc; R = Pri

Scheme 32

+

The reaction of CS1 with Co1"CO#7 results in the formation of more than eight di}erent sulfur!containing products\ similar to that with Fe2"CO#01[ Separation by column chromatography or bythin!layer chromatography gave compounds which could be isolated in low yields and identi_ed byx!ray di}raction analysis[ Reaction time\ solvents\ and the workup procedure all a}ect the productdistribution found[ Thus\ a 3 ] 0 mixture of the components in light petroleum gave "051# after areaction time of 7 h and puri_cation by thin!layer chromatography ð72CC0502Ł^ additionally\ isomershave also been isolated ð71IC2670Ł[ Wei described the preparation of "052# and unidenti_ed productsusing the same or a slightly modi_ed procedure ð73IC1862Ł^ some of the products are summarizedin Scheme 22[ Earlier results concerning these compounds have been reported from the group ofMarko and co!workers ð57JOM"00#196Ł[

5[00[2[1[00 Compounds with the SCFe1Co core

The 49!electron cluster compounds Fe1CoCp1"CO#4CSR "053# "a^ R�Me^ b^ R�CH1Ph# can beprepared by the reaction of the corresponding bridging thiocarbyne complexes ðCp"CO#Fe"m!CO#


Co(CO)3(CO)3Co

Co(CO)3

S Co(CO)3

Co(CO)3

(CO)3CoO

Co(CO)3(CO)3Co

Co(CO)3

SCo(CO)2

CoSS

Co(CO)3

Co(CO)2

CoS

Co(CO)3

S

+ (CO)9Co3CC

SCo(CO)2

CoS

Co(CO)3

(CO)2

(CO)2S

+ (CO)8Co3C

S

(162)

(163)

Co2(CO)8

CS2

8 h

(CO)2

CS2

24 h

Scheme 33

"m!SR#ŁPF5 with excess NaðCo"CO#3Ł "prepared in situ by combining Co1"CO#7 with _nely groundNaOH# in THF under UV photolysis at room temperature[ Extraction of the neutral clustercompounds with benzene and recrystallization from dichloromethaneÐhexane produces brownish!purple crystals[ Whereas "053a# is isolated in a yield of about 79)\ the similar route to "053b# givesthe compound in 17) yield but requires photolysis at 01>C[ Phosphines replace one CO group atthe Co atom when the reaction is carried out in dichloromethane to give "054# and "055# in goodyields "Table 1\ entries 0 to 5# as illustrated in Scheme 23 ð77JOM"283#072Ł[

CpFe

Co

FeCp

O

O

MeS

COPh2P

PPh2

CpFe

Co(CO)2

FeCp(CO)

O

O

SR

CpFe

Co(CO)PR3

FeCp(CO)

O

O

MeS

Cp(CO)Fe FeCp(CO)

SR

O

(166) a; PR3 = PMe3b; PR3 = PEt3c; PR3 = PCy3d; PR3 = PHPh2e; PR3 = PMePh2

Ph2P PPh2

+

Na[Co(CO)4]

PR3

(165)

(164) a; R = Meb; R = CH2Ph

Cy = Cyclohexyl

Scheme 34

5[00[2[1[01 Compounds with the SCCo1W core

Only one set of compounds of this type has been described[ The 37!electron cluster compounds"056a#Ð"056e# "Table 2# have been obtained by addition of Co1"CO#7 to an equilibrium mixture of


Table 1 Preparation of "054# and "055# from "053^ R � Me# by CO:phosphine exchange[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐEntry Product Phosphine Decomp[ temp[ Time Yield

">C# "h# ")#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ0 "055a# PPh2 097 8 821 "055b# PEt2 84 0[4 572 "055c# PCy2 84 01 433 "055d# PHPh1 89 4 524 "055e# PMePh1 45 "054# Ph1PCH1PPh1 89 34 46*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Table 2 Properties of the compounds "056a#Ð"056e#[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ"056# R2 R0 R1 Yield M[p[

")# ">C#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐa Ph CO1Me CO1Me 70 47b Me CO1Me CO1Me 55c Ph CF2 CF2 28d Me CF2 CF2 34e Me CO1Me H 79 013*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

the two isomers of the carbene complex "diphos#"CO#2W1CS1C1R0R1 in dichlormethane solution[After 01 h reaction time the compounds could be precipitated with hexane[ From "056e# two isomerswere formed according to the orientation of the R0CCR1 unit[ The yields of the compounds aregiven in Scheme 24 ð77JOM"283#072Ł[

PW

P Co

Co(CO)2

S

SO

R32

R32

R32

CO

R32

O

R32

R1

R2

R32

(167)

S S

R1 R2

CO

CO

COPW

P

CO

PW

P

CO

S

S

R2

CO

Co2(CO)8

R1

Scheme 35

(CO)2

5[00[2[2 Methanes Bearing One Selenium or One Tellurium Function and Three Functions Derivedfrom the Group 04 Element\ Metalloid and:or a Metal

The compounds bearing the SeC or TeC unit\ with few exceptions\ are restricted to samples withthe TMS group and thus contain the tris"trimethylsily#methyl function\ "TMS#2C[ This section refersmainly to work of the research groups of Sladky\ duMont\ and Arnold[


5[00[2[2[0 Compounds with the SeCN2 core

Only one compound in this series has been described\ by a Russian group in connection withcompounds containing the related SC"NO1#2 fragment[ The compound PhSeC"NO1#2 has beenprepared by addition of KðC"NO1#2Ł to a solution of PhSeCl in CH1Cl1 solution[ KCl was removedand the resulting dried oil was triturated with hexane^ the reaction could also be carried out withPhSeBr and the yield of the compound was about 099) in each case ð71IZV050Ł[ Reactions of thecompound with various M0Hal compounds have been described ð78IZV1095Ł[

5[00[2[2[1 Compounds with the SeCSi2 core

This section contains compounds of the general type "TMS#2CSeX in which the selenium atom isfurther bonded to either hydrogen\ alkyl\ aryl\ halogen\ chalcogen\ or gold[ The "TMS#2C group isabbreviated below as Tsi[ A list of compounds prepared by the groups of Sladky\ duMont andArnold along with conditions and yields are collected in Table 3 and a survey of reactions is shownin Schemes 25Ð27[

Table 3 Preparation and properties of compounds with the Si2CSe core[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐEntry Structure Color Preparation Yield Ref[

"m[p[^ >C# ")#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ0 "060# Red "193# TSiLi ¦ Se^ H1O\ O1 74CC07991 "064# ¦ Se:I1 84 82ZAAC"508#05822 "064# Red "192# "060# ¦ Cu^ 89 >C\ THF 35 89CB12143 "065# RedÐbrown "081# "060# ¦ Br1 84Ð87 82ZAAC"508#05824 "067# YellowÐbrown "190# "060# ¦ SO1Cl1 85 82ZAAC"508#05825 "066# BlackÐviolet "060# ¦ I1^ toluene 68 77CB10986 "068# Yellow "012# "067# ¦ Me2SiCN\ CH2CN 78 82ZAAC"508#05827 "079# Orange "039# "067# ¦ KSCN in CH1Cl1 53 82ZAAC"508#05828 "070# Yellow "83# "066# ¦ S^ toluene 4 82ZAAC"508#0582

09 "064# ¦ S:I1 in toluene 3700 "071# "066# ¦ Se^ toulene 4 82ZAAC"508#058201 "072# "066# ¦ S^ toluene 09 82ZAAC"508#058202 "073# Colorless "064# ¦ MeLi^ THF 42 78CB116803 "074# Colorless "064# ¦ PhLi 32 78CB116804 "063# Colorless "74# "064# ¦ TSiLi:THF 62 78CB116805 "069# Colorless "69# "064# ¦ TSiLi:THF 7 78CB116806 Pale yellow "058#"THF¦#HSO2CF2 82 82JA566607 "058# Light orange TSiLi ¦ Se^ DMF 62 82JA566608 "061# Colorless "dec[# "058# ¦ AuCl^ THF 54 82IC401519 "062# Colorless "073Ð078# "058# ¦ Ph2PAuCl^ ether 64 82IC401510 "069# ¦ Ph2PAuN"SiMe2#1 65*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

TsiLi has been reported to undergo insertion of two equivalents of selenium to give TsiSeSeLi"057# in THF solution ð74CC0799Ł and insertion of one equivalent of selenium to give "058# in thepresence of dimethoxyethane\ which on protonolysis leads to the hydride "069# ð82JA5666Ł^ additionof H1O and oxidation with O1 give bisðtris"trimethylsilyl#methylŁtriselenide\ TsiSeSeSeTsi "060#ð74CC0799Ł "Scheme 25#[

The middle selenium atom of "060# can be removed to give TsiSeSeTsi "064#\ which has been usedas starting material for a variety of other TsiSeR compounds ð78CB1168\ 89CB1214\ 82ZAAC0582Ł[

TsiLiSe/DME Se

TsiSeSeLiH2O2/O2

TsiSeSeSeTsiTsiSeLi•DMEH+/ether

TsiSeH TsiSeSeTsiCu

(170) (169) (168) (171) (175)

Scheme 36

The gold compounds "061# and "062# have been obtained by treatment of TsiLi =DME with AuClor AuClPPh2\ respectively\ as depicted in Scheme 26 ð82IC4015Ł[


The production of TsiSeH "069# and TsiSeC3H6O "063# from TsiSeSeTsi "064# in THF wasreported to be a result of a single electron!transfer reaction "SET# via the TsiSe = radical ð78CB1168Ł[

TsiSeLi•DMEPh3PAuCl

TsiSeAuPPh3

(173) (169)

AuClSe Au Se

Au

SeAuSe

Au

TMS

TMS TMS

TMS

TMS TMS

TMS

TMS

TMS

TMS

TMS

TMS

(172)

Scheme 37

TSi = (TMS)3C

As shown in Scheme 27 the Se0Se bond in the diselenide "064# can be cleaved by various oxidizingagents[ While Br1 ð89CB1214Ł and I1 ð77CB1098Ł lead to the corresponding halides "065# and "066#\respectively\ the chloride "067# is obtained by reacting with SO1Cl1^ the introductions of pseudo!halogen CN− or SCN− can by achieved by treating the chloride with the appropriate TMS!Xð82ZAAC"508#0582Ł[ A reversible reaction with elemental sulfur or selenium generates a mixtureof further chalcogen!rich derivatives "070Ð072# which can also be obtained starting from "064#ð82ZAAC0582Ł[

The action of LiR "R�Me\ Ph# on the diselenide "064# generates the species TsiSeMe "073# andTsiSePh "074#\ respectively ð82ZAAC"508#0582Ł[

O SeTsi

(174)

(170) +

TsiLi

TsiSeSeTsi

(175)

I2SO2Cl2

TsiSeCl TsiSeI

(178) (177)

TsiSeBr

(176)

TsiSeR

(184)(185)

TSiSeSeSeTsi(171)

TsiSeSeSeSeTsi(182)

HgTSiSeSSeTsi

(181)TsiSeSSSeTsi

(183)

HgSe S

; R = Me; R = Ph

RLi Br2

TMS-X

TsiSeX

(179)(180)

; X = CN; X = SCN

Scheme 38

Tsi = (TMS)3C

5[00[2[2[2 Compounds with the TeCSi2 core

Most of the compounds which have been described with the SeCSi2 core are also known with theTeCSi2 core and\ similarly to the selenium derivatives\ only compounds with the TMS group areknown[ Thus\ compounds of the general type "TMS#2CTeX in which the tellurium atom is furtherbonded to hydrogen\ alkyl\ aryl\ halogen\ chalcogen\ or some transition metals have been preparedby the same working groups as reported for the corresponding selenium compounds[ A list ofcompounds along with conditions and yields are collected in Table 4 and a survey of reactions isshown in the Schemes 28Ð39[

As with selenium\ insertion of two equivalents of tellurium into the C0Li bond of TsiLi producesTsiTeTeLi "075#\ which can also be obtained by addition of tellurium to the monotelluride "076#[Oxidation of the lithium salt "075# with H1O:O1 generates the tritelluride TsiTeTeTeTsi "077# from


Table 4 Preparation and properties of compounds with the Si2CTe core[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐEntry Structure Color Preparation Yield Ref[

"m[p[\ >C# ")#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ0 "075# "076# ¦ Te 74CC07991 "076# Orange "030Ð034# THF!adduct^ TsiLi ¦ Te\ THF 45 82JA56662 "078# ¦ Li 74CC07993 "077# RedÐblack From decomp[ of "089# 74JOM"184#C04 "075# ¦ H1O:O1 59 74CC07995 "078# "076# ¦ Se 74CC07996 "089# "075# ¦ ClP"But#1^ not isol[ 74JOM"184#C07 "080# "076# ¦ SeCl1 74CC07998 "081# Red "080# ¦ Hg in pentane 74CC0799

09 "078# ¦ Se\ ultrasound 29 h 84 80OM109000 "082# "076# ¦ ClP"But#1 74JOM"184#C001 "083# From decomp[ of "082# 74JOM"184#C002 "084# Yellow "042Ð043# "076# ¦ H¦ in ether 70 82JA566603 "085# Colorless "076# ¦ AuCl 31 82IC401504 "086# Yellow "076# ¦ ClAuPPh2 54 82IC401505 "087# "076# ¦ Cp1TiCl1^ unstable 82JA43406 "088# Red "076# ¦ Cp1ZrCl1 46 82JA43407 "199# Orange "078# ¦ S\ ultrasound 29 h 84 80OM109008 "190# BlueÐblack "009# "078# ¦ SO1Cl1 84 78CB014419 "191# BlueÐblack "009# "078# ¦ Br1 84 78CB014410 "192# BlueÐblack "009# "078# ¦ I1 84 78CB014411 "193# Bright yellow "79# Tsi1Te1 ¦ RLi in THF 50 78CB116812 "192# ¦ MeLi in THF 74 78CB014413 "194# Bright yellow "36# Tsi1Te1 ¦ RLi in THF 46 78CB116814 "192# ¦ PhLi in THF 79 78CB014415 "195# Yellow "039#a "192# ¦ AgCNb 61 80CB002016 "196# Dark red "014#a "192# ¦ AgSCNb 76 80CB002017 "197# Red "029#a "192# ¦ AgSeCNb 71 80CB002018 "198# Red "½019#a "192# ¦ AgNCOb 62 80CB002029 "109# Deep red "024#a "192# ¦ AgN2

b 80CB002020 "192# ¦ TlOEt:TMS!N2

b 7321 "100# Dark red "034#a "192# ¦ Ag1NCNb 76 80CB002022 "101# Orange "039#a "192# ¦ K1NSNb 81 80CB002023 "102# Colorless "58# "078# ¦ TSiLi in THF 65 78CB1168*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐa With decomposition[ b In benzene[

which the middle tellurium atom can be removed with mercury to give "078#^ the latter compoundis also formed by oxidation of the lithium salt "076# with elemental Se ð74CC0799Ł[ Reaction of "075#with ClP"But#1 produces the ditellurophosphine "089# ð74JOM"184#C0Ł[ The reactions are summarizedin Scheme 28[

TsiLi

Te

TsiTeTeLi

(186)

H2O/O2

TsiTeTeTeLi

(188)

Te

Hg

TsiTeLi

(187)

Se

TsiTeTeLi

(189)

TsiTeTePBut2

(190)

ClPBut2

Scheme 39

Li

TsiTeLi "076# is starting material for a variety of derivatives as depicted in Scheme 39[ Thiscompound has also been described as the THF solvate TsiTeLi"THF#1 ð82JA5666Ł[ Action of SeCl1leads to "080# ð74CC0799Ł\ which can be deselenated to "081#\ while reaction with ClP"But#1 gives thetellurophosphine "082#[ At room temperature this tellurophosphine is not stable and converts into


"083# and TeðP"But#1Ł1 ð74JOM"184#C0Ł[ With tri~ic acid and the THF solvate "076# the correspondingacid "084# is obtained ð82JA5666Ł[

The THF solvate "076# is also the starting material for some transition metal derivatives[ WithAuCl and Ph2PAuCl the tetranuclear species "085# and the mononuclear compound "086#\ respec!tively\ have been prepared^ the structure of the tetranuclear compound is identical to the structureof the corresponding selenium compound "061# ð82IC4015Ł[ LiCl elimination proceeds also withCp1MCl1 "M�Ti\ Zr#\ to give the Cp1M"TeTsi#1 compounds "087# and "088#\ respectively ð82JA434Ł[

Scheme 40

TsiTeH

H+

TsiTeLi

(187)

TsiTePBut2

(193)

SeCl2TsiTeSeSeTeTsi

(191)

Hg

TsiTeSeTeTsi

(192)

TsiTeAuPPh3

(197)

ClPBut2

(195)

TsiTeTsi

(194)

AuCl

ClAuPPh3

Cp2MCl2

Au4(TeTsi)4

(196)

Cp2M(TeTsi)2

(198); M = Ti(199); M = Zr

The chemistry of TsiTeTeTsi "078# is summarized in Scheme 30[ Ultrasonic activation in thepresence of elemental sulfur or selenium leads to the insertion of one chalcogen molecule to give"TsiTe#1E "199^ E�S#\ "081^ E�Se# ð80OM1090Ł[

The tellurohalogenides "190#Ð"192# have been prepared by the reaction of "078# with SO1Cl1\ Br1\or I1\ respectively[ The chloride "190# can be alkylated with MeLi to give "193# or arylated withPhLi or PhMgBr to produce "194# ð78CB0144Ł^ both compounds can also be prepared from Tsi1Te1

and the corresponding RLi ð78CB1168Ł[ Halogen exchange in the iodide "192# with various AgXcompounds leads to the compounds "195#Ð"109#[ A similar reaction with two equivalents of theiodide and Ag1NCN or Ag1NSN generates the carbodiimide "100# and the sulfur diimide "101#\respectively[ The compound TsiTeOEt was mentioned in a dissertation ð80CB0020Ł[ Finally\ theaddition of TsiLi to a solution of "078# leads to the incorporation of a THF molecule to produceair!stable "102# "m[p[ 58>C# in about 65) yield ð78CB1168Ł[

TsiTeETeTsi

(200); E = S(192); E = Se

ETsiTeTeTsi

(189) (201); X = Cl(202); X = Br(203); X = I

TsiTeX

O TeTsi

(213)(206); Y = CN(207); Y = SCN(208); Y = SeCN(209); Y = NCO(210); Y = N3

TsiTeY

TsiLi/THFAgY LiR

(204); R = Me(205); R = Ph

TsiTeR

(211); E = C(212); E = S

TsiTeNENTeTsi

Ag2NEN

Scheme 41


6.12Functions Containing at LeastOne Group 15 Element (and NoHalogen or Chalcogen)DUNCAN CARMICHAEL, ANGELA MARINETTI andPHILIPPE SAVIGNACDCPH–Ecole Polytechnique, Palaiseau, France

5[01[0 METHANES BEARING FOUR GROUP 04 ELEMENTS 259

5[01[0[0 Four Similar Group 04 Element Functions 2595[01[0[0[0 Four nitroèn functions 2595[01[0[0[1 Four phosphorus functions 254

5[01[0[1 Three Similar and One Different Group 04 Element Functions 2555[01[0[1[0 Three nitroèn functions 2555[01[0[1[1 Three phosphorus functions 255

5[01[0[2 Two Similar and Two Different Group 04 Element Functions 2565[01[0[2[0 Two nitroèn functions 2565[01[0[2[1 Two phosphorus functions 256

5[01[1 METHANES BEARING THREE GROUP 04 ELEMENTS AND A METALLOID OR AMETAL 257

5[01[1[0 Three Similar Group 04 Elements 2575[01[1[0[0 Three nitroèn functions 2575[01[1[0[1 Three phosphorus functions 258

5[01[2 METHANES BEARING TWO GROUP 04 ELEMENTS AND METALLOID AND:OR METALFUNCTIONS 269

5[01[2[0 Two Similar Group 04 Elements 2695[01[2[0[0 Two nitroèn functions 2695[01[2[0[1 Two phosphorus functions 269

5[01[3 METHANES BEARING ONE GROUP 04 ELEMENT AND METALLOID AND:OR METALFUNCTIONS 261

5[01[3[0 Nitroèn Functions 2615[01[3[1 Phosphorus Functions 261

5[01[3[1[0 One phosphorus and three silicon functions 2615[01[3[1[1 One phosphorus\ one metal and two silicon functions 262

5[01[3[2 Arsenic or Antimony Functions 263

248


5[01[0 METHANES BEARING FOUR GROUP 04 ELEMENTS

5[01[0[0 Four Similar Group 04 Element Functions

5[01[0[0[0 Four nitrogen functions

Cyclic\ acyclic and spirocyclic compounds bearing four nitrogen functions are known[ In allcases\ at least two of the nitrogen functions are identical\ and totally symmetrical compoundsalso exist[ Examples of this class of compound\ where the tetracoordinated carbon is bound tothe nitrogen atom of amino\ dialkyl or diarylamino\ ~uoroamino\ amido\ hydrazino\ nitro\ andisocyano functions\ have been prepared[ No single method has been shown to be compatible withevery one of these functions\ but a number of syntheses are reasonably general[ These are detailedbelow[

"i# By nucleophilic exchanè of chlorine atoms

"a# From 1\1!dichloro!3\4!imidazolidinediones and analoùes[ The 1\1!dichloro!3\4!imidazolidi!nediones react with primary or secondary amines to give the corresponding tetraaminomethanes\by successive replacement of both chlorine atoms[ Dehydrohalogenation may be e}ected by anexcess of the amine itself\ or by the addition of bases such as triethylamine or K1CO2 "Equation "0#and Table 0#[

N

N

R1

R2

O

OCl

Cl+ 2R3

2NH

N

N

R1

R2

O

ONR3

2

NR32

(1)

Table 0 Nucleophilic exchange of chlorine atoms with amines on 1\1!dichloro!3\4!imidazolidinediones[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

YieldR0\ R1 Reaènts Conditions ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐMe1CH morpholine Dioxane\ Et2N\ 14>C\ 1 h 17 69CB655Me1CH N!Me!piperazine Dioxane\ Et2N\ 14>C\ 1 h 52 69CB655Me1CH pyrrolidine Dioxane\ 3 equiv[ amine\ 14>C 35 62CB1204Me1CH piperidine Dioxane\ 3 equiv[ amine\ 14>C 70 62CB12043!NO1C5H3 morpholine Dioxane\ 3 equiv[ amine\ 14>C 64 62CB12041!MeC5H3 morpholine Dioxane\ 3 equiv[ amine\ 14>C 76 62CB1204C5H00 morpholine Dioxane\ 3 equiv[ amine\ 14>C 52 62CB1204*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

The benzylthiolate leaving group may also be used in place of chloride ð67JPR224Ł[ Diamines leadto spirocyclic derivatives "Equation "1# and Table 1#[ 1\1?!Spiroimidazolidine!3?\4?!dione derivativeshave been patented as stabilizers for color photographic materials ð65GEP1359229Ł[

N

N

R1

R2

O

OCl

Cl+

N

N

R1

R2

O

ONR3

NR3

(2)HR3N

HR3N

Et3N

dioxane, 25 or 60 °C

A related reaction of 1\1!dichloro!1\5!dihydro!3\5!pyrimidinediones with simple or chelatingamines proceeds through a substitution of both chlorine atoms to give open or spirocyclic tetraa!mines\ respectively "Equation "2##[ Yields are moderate to good "Table 2# ð77CZ271Ł[

250Four Group 04 Elements

Table 1 Nucleophilic exchange of chlorine atoms with diamines on 1\1!dichloro!3\4!imidazolidinediones[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐYield

R0\ R1 Rea`ents ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐMe1CH "MeNHCH1#1 34 69CB655C5H00 "MeNHCH1#1 41 69CB655Me\ C5H00 "MeNHCH1#1 00 69CB655Me1CH 0\1!"NH1#1C5H3 65 69CB655c!C5H00 0\1!"NH1#1C5H3 81 69CB6553!MeC5H3 0\1!"NH1#1C5H3 54 69CB655H\ Ph 0\1!"NH1#1C5H3 56 67JPR224H\ 1!ClC5H3 0\1!"NH1#1C5H3 44 67JPR224H\ PhCO 0\1!"NH1#1C5H3 67 67JPR224H\ PhCH1 0\1!"NH1#1C5H3 46 67JPR224Me1CH triphenylguanidine 27 69ZC29c!C5H00 triphenylguanidine 04 69ZC29*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

+ amine

N

NR2

R3 Cl

Cl

O

O

R1

R1

N

NR2

R3 NR42

NR42

O

O

R1

R1

(3)

Table 2 Nucleophilic exchange of chlorine atoms with amines on 1\1!dichloro!1\5!dihydro!3\5!pyrimidinediones[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐYield

R0\ R1\ R2 Rea`ents Conditions ")#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐc!C5H00^ Cl^ Cl pyrazole THF\ 14>C 68c!C5H00^ Cl^ Cl phenoxazine THF\ 14>C 25c!C5H00^ Cl^ Cl "PhNHCH1#1 THF\ 14>C 33c!C5H00^ Cl^ Cl 3!Ph!0\1!"NH1#1C5H2 THF\ 14>C 25Ph^ Ph^ Cl phenoxazine THF\ 14>C 67Ph^ Ph^ Cl 0\1!"NH1#1C5H3 THF\ 14>C 12Me1CH^ Cl^ Cl tetramethyl!1\1?!diimidazole THF\ Et2N\ 14>C 23c!C5H00\ Me\ Me "PhNHCH1#1 THF\ 14>C 33c!C5H00\ Me\ Me homopiperazine THF\ K1CO2\ 14>C 07*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

"b# From 1!chloro\1!aminoiminium salts[ Tetrakis"dimethylamino#methane\ the _rst tetra!aminomethane described in the literature\ was synthesized in 69) yield by allowing tetra!methylchloroformamidinium chloride to react with lithium dimethylamide in benzene at roomtemperature "Equation "3## ð55JA1774Ł[ Homologous tetraaminomethanes\ prepared analogously\have been patented as aminating agents\ herbicides\ insecticides\ bactericides\ and catalysts forurethane polymerization ð69USP2440307Ł[

(4)Cl

Me2N

Me2N

Me2N

NMe2

NMe2

NMe2

+

Cl–2Me2NLi

C6H6, 25 °C70%

The preparation of a dibenzoanellated tetraaminomethane from 1!chloro!0\2!dimethyl!benzo!imidazolium tetra~uoroborate and N\N!dimethyl!ortho!phenylenediamine has been reported "Equa!tion "4## ð57CB0026Ł[

(5)Cl

+

BF4–

Et3N

MeCN, 25 °C32%

N

N

Me

Me

+

NHMe

NHMe N

N

N

N

Me Me

MeMe


This synthetic methodology has been extended to the synthesis of the tetraazamethanes indicatedin Scheme 0[ The properties of these compounds were subsequently investigated by photoelectronspectroscopy ð75JOC269Ł[

N

N

N

N

Me Me

MeMe

N

N

Me

Me

N

N

Me

Me

N

N

Me

Me

N

N

Me

Me

Scheme 1

"c# Tetrakis"0!pyrazolyl#methane from CCl3[ Tetrakis"0!pyrazolyl#methanes have been widelyinvestigated as polydentate ligands in transition metal organometallic complexes[ The parent com!pound was _rst synthesized in low yield "01)# from carbon tetrachloride and an alkali!metalpyrazolide ð69JA4007Ł[ The conversion was improved slightly "19)# under solidÐliquid phase transfercatalysis conditions "Equation "5## ð73OPP188Ł[ Nonetheless\ these syntheses remain less e.cient thana two!step procedure starting from phosgene and sodium pyrazolide salts "see Section 5[01[0[0[0["v##[

(6)N

NH4 + CCl4KOH, K2CO3

Bun4NHSO4, CCl4

NN C

4

"d# Tetrakis"di~uorosulfoximidoyl#methane from CCl3[ The title compound may be prepareddirectly from CBr3 and the corresponding organomercury reagent\ but the reaction gives a numberof products and yields are poor] the desired compound was only detected by mass spectroscopy[ Amore practical synthesis involves the interaction of carbon tetrachloride with bis"di~uoro!sulfoximidoyl#mercury and treatment of the resulting intermediate with tris"di~uorosulf!oximidoyl#borane[ Nonetheless\ the yield remains low "5)# "Scheme 1# ð68CB0078Ł[

Hg(NSOF2)2

CCl4

145 °C, 20 h82%

B(NSOF2)3

–78 °C, 3 h6%

C(NSOF2)4F2C(NSOF2)2

Scheme 2

"ii# By addition to carbonÐnitro`en double bonds

A wide variety of NH functionalities add to activated carbonÐnitrogen double bonds[ Thus\ammonia\ 3!cyanoaniline\ 3!tri~uoromethylaniline\ hydrazine\ tri~uoroacetylhydrazine and suc!cinimide react with penta~uoroguanidine at low temperatures to give the corresponding tetraa!zamethanes "Scheme 2# ð62JOC0964Ł[ In the case of relatively basic amines\ such as NH2\ BunNH1

and Me1NH\ spontaneous elimination of HNF1 occurs below room temperature\ to give a poly!~uoroguanidine having a di}erent substitution pattern[ These reactions are dan`erous\ and shouldbe performed in polar solvents in order to reduce the risks of explosion] suitable protective equipmentshould be used durin` all phases of work[

R1R2NH

dimethylether–63 °C

20 °CNF

F2N

F2N

F2N

F2N

NHF

NR1R2

NF

F2N

R1R2N

Scheme 3

+ F2NH

The _rst!formed tetraaminomethanes "Scheme 2# are useful synthetic intermediates[ Bis"di!~uoroamino#"~uoroamino#aminomethane may be treated with elemental ~uorine at low tem!perature to give\ amongst other products\ the highly explosive tetrakis"di~uoroamino#methaneð61USP2578459\ 61USP2552510\ 62JOC0964Ł\ C"F1N#3 which has been patented as a rocket!propellantoxidizer "Equation "6## ð61USP2588983\ 62USP2644393Ł[


F2/N2

–30 °C, 5 hF2N

F2N

NHF

NH2C(NF2)4 (7)

Similarly\ ammonia adds to ðbis"di~uoroamino#~uoromethylazoŁtri~uoroformamidine giving anunstable adduct\ which undergoes low temperature ~uorination[ Fluoropentakis"di~uoroamino#azomethane is formed in low yield by this method "Scheme 3# ð61IC307Ł[

N

F2N

N

(F2N)2FC

NF

N

F2N

N

(F2N)2FC

NHF

NH2

N N CF(NF2)2(F2N)3C

NH3

CCl2F2, –96 °C, 2.5 h

F2/N2

CCl2F2, –110 °C, 6 h10%

Scheme 4

Penta~uoroguanidine may be subjected to an analogous addition of isocyanic acid\ which givesbis"di~uoroamino#~uoroaminomethyl isocyanate[ This isocyanate and the other derivatives describedin this section are reported to be very powerful explosives which are extremely sensitive to impact\friction\ and perhaps temperature chanès[ Quantities as small as 099 m` should be reàrded asdanèrous[ The _rst formed isocyanate product may react with a further equivalent of isocyanicacid to give the cyclic derivative shown in Equation "7# ð62JOC0979Ł[

(8)HNCO

urea (cat.), –30 °C, 3 hNF

F2N

F2N

F2N

F2N

NHF

NCO

N

N

HN

O

O

F

F

NF2

NF2+

Other tetraazamethanes may be obtained from bis"di~uoroamino#~uoroaminomethyl isocyanate[Treatment with elemental ~uorine alone permits substitution of hydrogen by ~uorine without acompeting reaction at the isocyanate moiety[ However\ ~uorination in the presence of sodium~uoride gives tetrakis"di~uoroamino#methane "81)# "Scheme 4# ð62JOC0977\ 62USP2622259Ł[

F2/He

0 °CF2N

F2N

NHF

NCO F2/NaFNCO

F2N

F2N

F2N NF2

F2N

F2N

F2N

Scheme 5

Addition of ethanol to bis"di~uoroamino#~uoroaminomethyl isocyanate results in the trans!formation of the NCO function into the corresponding ethylcarbamate ð62JOC0979Ł[ Tris"di~uoroamino#methyl isocyanate also undergoes addition of alcohols\ water and amines at theisocyanate function "Table 3# ð62JOC0972Ł[

Table 3 Addition of water\ alcohols and amines at the isocyanate function[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

YieldIsocyanate Reaènts and conditions Products ")#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ"F1N#1"HNF#C"NCO# EtOH\ −085:14>C "F1N#1"NHF#C"NHCO1Et#"F1N#2C"NCO# HOCH1CH1OH\ 14>C ""F1N#2CNHCO1CH1#1 69"F1N#2C"NCO# H1C1CHCH1OH\ 14>C "F1N#2CNHCO1CH1CH1CH1 80"F1N#2C"NCO# ether\ NH2\ −085:14>C "F1N#2CNHCONH1 62"F1N#2C"NCO# ether\ 9[2NH2\ −085:14>C ""F1N#2CNHCO#1NH 49"F1N#2C"NCO# "H1N#1\ MeCN\ −085:14>C ""F1N#2CNHCONH#1 40"F1N#2C"NCO# H1O "F1N#2CNH1

"F1N#2C"NCO# "F1N#2CNH1:Ph2PO ""F1N#2CNH#1CO*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Although most of the compounds described in this section are high explosives\ some relatedmethodologies have been applied to more classical synthetic procedures[

Thus\ 0\2!bis"methoxycarbonyl#!S!methyl isothiourea "BMMTU#\ a widely used reagent for thepreparation of benzimidazole!1!carbamates from ortho!phenylenediamines\ reacts in slightly acid


media with 1!aminobenzamides\ to give 1\1!biscarbamates in yields ranging from 45) to 64)"Scheme 5#[ This reaction permits the synthesis of potential medicinal products\ fungicides andantiparasitic agents ð89S040Ł[

X

Y

Z

NO2

NH2

O

X

Y

Z

NH2

NH2

O

H H 61H

X

Y

Z

NH

NH

O

OMe OMe OMe

YX

56

NHCO2Me

NHCO2Me

Yield (%)Z

i ii

i, Raney - Ni, N2H4, MeOH, 25 °C, 3 h

ii, MeO2CN=C(SMe)NHCO2Me, MeOH, MeCO2H, reflux, 2 hOMe OMe H 75

Scheme 6

The reaction of two equivalents of isocyanate with pentasubstituted guanidines gives a cyclo!adduct having an s!triazine structure[ This reaction does not appear to be completely general[ Thus\pentamethylguanidine reacts with both phenyl and methyl isocyanate\ but N!phenyl!tetramethylguanidine undergoes reaction with methyl isocyanate but not with phenyl isocyanate[With N!phenyltetramethylguanidine and an equimolar mixture of the two isocyanates\ an unsym!metrically substituted s!triazine is produced "Equation "8## ð57TL4926Ł[

2R1NCO

ether, RTNR2

R12N

R12N

N

N

N

O

O

R2

R1

R1

NR12

NR12

R1, R2 = Me, C6H5

(9)

"iii# By addition to nitroènÐnitroèn double bonds

Azodicarboxylate esters react either with trinitromethane in dioxane ð64IZV1727Ł\ or with itsmercury salts in water ð66IZV0452Ł\ to give "trinitromethyl#hydrazine derivatives[ Nitroform reactsanalogously with azocarboxamides "Scheme 6#[

EtO2CN NCONHMe (O2N)3C N NHCO2Et

CONHMe

i, H2O, 20 °C

ii, HCl conc.EtO2CN NCO2Et

+ (O2N)3CHdioxane, 20 °C, 4 d

90%

+ Hg(C(NO2)3)2 (O2N)3C N NHCO2Et

CO2Et88%

Scheme 7

"iv# From carbanions bearin` two nitroèn substituents

Ammonium trinitromethanide reacts readily with nitryl ~uoride to form tetranitromethane inexcellent yield[ Trinitromethane itself is ionized su.ciently in acetonitrile to interact directly withnitryl ~uoride but the yield is slightly poorer in this case "Equation "09## ð60IZV0483\ 63IZV804Ł[

(10)NO2F

MeCN90%

(O2N)3C– NH4+ C(NO2)4

Reaction of bis"benzotriazolyl#methane with n!butyllithium and tosyl azide gave the èm!diazidocompound in moderate yield] the expected monoazido compound appears to be more reactive than


the starting material[ A further Staudinger phosphorylation reaction with triphenylphosphine gavea product\ presumed to be the corresponding bis"triphenylphosphoranylidene# compound\ whichwas too unstable to be isolated "Scheme 7# ð89JCR"S#229Ł[

BunLi, TsN3

THF, –78 °C22%

NN

N

NN

N

NN

N

NN

N N3

N3 PPh3

THF, 25 °C, 5 h

PPh3N

N PPh3

N

N

N

N

N

N

Scheme 8

"v# Miscellaneous syntheses

This section comprises a number of unrelated synthesis of which two are particularly important[The _rst constitutes the most e}ective preparation of tetranitromethane\ which is obtained in

approximately 59) yield by the reaction of anhydrous nitric acid with acetic anhydride below 09>C"Equation "00## ð44OSC"2#792Ł[ The product is a high explosive\ and should be puri_ed only by steamdistillation[ The synthesis has been adapted to the preparation of the labelled compound C"NO1

04#3in 39) overall yield from sodium nitrate ð89MI 501!90Ł[

10 °C4(MeCO)2O + 4HNO3 C(NO2)4 + 7MeCO2H + CO2 (11)

The second important synthesis produces tetrakis"0!pyrazolyl#methanes\ which have been pre!pared through a two!step process from the appropriate pyrazolide salt and phosgene[ Thermolysisof the intermediate 0\0?carbonyldipyrazole at 089>C in the presence of cobalt"II# chloride inducesan autocondensation reaction which gives the tetrakis"0!pyrazolyl#methanes in a total yield of 49)"Scheme 8# ð62CJC1337Ł[

COCl2

ether, reflux80%

CoCl2

190 °C, 16 h50%

NN C

4

NN CO

2

NN– Na+

Scheme 9

Interaction of 0\3\6\09!tetraazacyclododecane and ethyl orthocarbonate in acidic ethanol givessolutions which contain a tricyclic guanidinium ion!amino compound] the reaction proceeds innearly quantitative yield[ The corresponding covalent tetracyclic tetraazatridecane may be obtainedby neutralization\ extraction into benzene\ and subsequent drying by azeotropic distillation "Scheme09#[ The conformation of the two macrocycles\ and the equilibrium which relates them\ was studiedby NMR spectroscopy ð63T0658Ł[

C(OEt)4, HCl

EtOH

NaOH

C6H6, H2ONH HN

HNNH

N N

NN

Scheme 10

N N

NNH+

Cl–

5[01[0[0[1 Four phosphorus functions

Very few papers dealing with the synthesis of this class of compounds have appeared[ Nonetheless\a number of patents describing the use of methanetetraphosphonic acid and its derivatives in


detergents ð64USP2781565Ł or as chelating agents for heavy metal ions ð73USP3339535Ł have beendisclosed[

Chlorodimethylphosphine displaces all four chlorine atoms of carbon tetrachloride\ to givetetrakis"dichlorodimethylphosphoranyl#methane in 71) yield[ The pentacoordinated phosphorusderivative was converted into the corresponding oxide upon basic hydrolysis "79) yield# "Scheme00#[ The reaction is not general and fails for reagents such as PCl2 and MePCl1\ presumably becauseof their lower electron density at the phosphorus atom ð56ZOB1402Ł[

NaOH, H2O

81%

CCl4

160 °C, 3 h82%

Me2PCl C[Me2PCl2]4 C[P(O)Me2]4

Scheme 11

The only spiroð1[1Łtetraphosphapentane which is known to date was prepared by the reaction ofcarbon tetrachloride with 0\1!dipotassium di!tert!butyldiphosphide\ in 1) yield after chro!matography on alumina[ Of the two anti!isomers which are observed\ the sterically more hinderedone converts slowly into the favored isomer at room temperature "Scheme 01# ð72AG"E#521Ł[

CCl4

pentane, –78 °C(ButP—PBut)2– 2K+

PP

P

P

But

But

But

But

PP

P

P

But

But

But

But

Scheme 12

+

5[01[0[1 Three Similar and One Different Group 04 Element Functions

5[01[0[1[0 Three nitrogen functions

Only two compounds bearing three nitrogen functions are known] both are cyclic compoundscontaining three nitrogens and a phosphorus atom[ Both syntheses involve the participation of aphosphorus substituted C0N double bond\ and in each case two of the nitrogen atoms are includedin the ring[

In the _rst case\ the interaction of diethyl phosphite with diphenylcarbodiimide gave an inter!mediate amidinophosphinic acid which underwent a ð1¦1Ł cycloaddition reaction with phenylisocyanate[ The _nal product is obtained in 54) yield "Scheme 02# ð70ZOB0924Ł[

(EtO)2P(O)HPhN • NPh

PhNCO

80 °C, 5 h65%

PhN

NHPh

P(O)(OEt)2

N

N

OPh

PhPhHN

(EtO)2(O)PScheme 13

In the second case\ two equivalents of C!phosphorylated C!chlorohydrazones are reacted withthe potassium salt of alanine[ Both the amino and the carboxylate groups act as nucleophilesresulting in substitution of the chlorine atom of the phosphorylated substrate[ The linear productis converted\ through the steric pressure\ into the cyclic tautomer by addition of the N0H functionto the C1N double bond "Scheme 03# ð89ZOB0879Ł[

5[01[0[1[1 Three phosphorus functions

The only representatives of this class of compound bear one nitrogen and three phosphorusfunctions[ All the synthetic methods involve at least one MichaelisÐArbuzov type reaction as anintermediate step[

Reactions between triethyl phosphite and trichloromethylamines or trichloromethyl isocyanatea}ord tris"diethoxyphosphinyl#methylamines or isocyanates\ respectively "Equation "01# and Table 4#[


H2N CO2– K+

(4-O2NC6H4)NHN

P(O)(OMe)2

Cl

(4-O2NC6H4)NHN

HN-CHMe-C(O)

P(O)(OMe)2

N

C6H4(4-NO2)

NH(CO)-P(O)(OMe)2 HN

N

N

O

C6H4(4-NO2)

C(O)P(O)(OMe)2

NHNHC6H4(4-NO2)(MeO)2(O)P

+

Scheme 14

(12)3(EtO)3P + ZCX3 ZC[P(O)(OEt)2]3

Table 4 Reactions of triethyl phosphite with trichloromethylamines or iso!cyanate[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐYield

ZCX2 Conditions ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ"Me1N#CCl2 CH1Cl1\ −39>C\ 0 h 60 61ZOB0058"0!morpholino#CCl2 CH1Cl1\ −39>C\ 0 h 66 61ZOB0058"OCN#CCl2 toluene\ 89>C\ 0[4 h 45 62ZOB433"OCN#CBr2 toluene\ 89>C\ 0[4 h 12 78ZOB460"Me1N#CCl2 CH1Cl1\ −79:14>C 63GEP1126768*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Unsymmetrically substituted tris"phosphoryl#methylanilines were obtained transiently through atwo!step synthesis starting from N!phenylcarbonimidic dichloride[ An initial MichaelisÐArbuzovreaction between a trialkyl phosphite and the dichloroimine led to the corresponding bis"phos!phoryl#imine which was then reacted with various R1P"O#H compounds] addition of the P0Hfunction to the C1N double bond a}orded the tris"phosphoryl#methylanilines[ These compounds\which were originally thought to be stable ð61JPR76Ł\ rearrange spontaneously by migration of oneof the phosphoryl groups from the carbon to the nitrogen atom "Scheme 04# ð61JPR858\ 75JPR120Ł[

Cl2C NPh [R2P(O)]2C NPh

R2P(O)H[R2P(O)]2C NPh PhHN

P(O)R2

P(O)R2

P(O)R2 PhN

P(O)R2

P(O)R2R2(O)P

2R2POR +

Scheme 15

5[01[0[2 Two Similar and Two Different Group 04 Element Functions

5[01[0[2[0 Two nitrogen functions

Only one report of compounds bearing two nitrogen functions exists[Treatment of a benzene solution of amidines with chlorobis"diethoxyphosphonyl#methyl iso!

cyanate in the presence of triethylamine readily yields cyclic s!triazin!1"0H#!ones "Equation "02##ð64ZOB1982Ł[

+NHEt3N

C6H6, 20 °C, 2 hR

H2NNCO

Cl

(EtO)2P(O)

(EtO)2P(O) N NH

HNO

R

P(O)(OEt)2

P(O)(OEt)2

(13)

R = CCl3, 79%; Ph, 75%

5[01[0[2[1 Two phosphorus functions

See Section 5[01[0[2[0[


5[01[1 METHANES BEARING THREE GROUP 04 ELEMENTS AND A METALLOID ORA METAL

5[01[1[0 Three Similar Group 04 Elements

5[01[1[0[0 Three nitrogen functions

Compounds bearing three nitrogen functions essentially comprise derivatives of trinitromethane[In cases where they are not explicitly described as stable\ they are probably best treated as explosiveand should be handled with care[

The most widely studied reagent of this class is bis"trinitromethyl#mercury which may be easilyprepared\ in 79) yield\ by reaction of HgO with trinitromethane in ether at room temperature"Equation "03## ð59IZV494Ł[

HC(NO2)3 + HgOether

15 min(14)Hg[C(NO2)3]2

The interaction of this reagent with a wide range of ethers\ aliphatic and aromatic nitrocompounds\ nitramines and halocarbons has been investigated[ The molecular complexes which areformed have been studied by IR and NMR spectroscopy[ A number of lead references may beconsulted ð57IZV1728\ 58IZV1293\ 61MI 501!90Ł[

Bis"trinitromethyl#mercury undergoes metathesis reactions with R1Hg species to a}ord the mixedderivatives RHgC"NO1#2 "Equation "04##[ In the case where R�Bun\ the direct reaction of tri!nitromethane with dibutylmercury in ethanol leads to the same product ð56JOM"8#4Ł[

(15)HgR2 + Hg[C(NO2)3]2

EtOH

reflux, 6 hRHgC(NO2)3

R = Ph, 86%; Bun, 50%

The related aryl"trinitromethyl#mercury may also be prepared from diphenylmercury and tetra!nitromethane in a wide range of solvents such as MeCN\ sulfolane and chloroform\ probably by aradical mechanism "Equation "05## ð63ZOR0682Ł[

(16)HgPh2 + C(NO2)4

sulfolane

80 °C, 10 h46%

PhHgC(NO2)3

Bis"trinitromethyl#mercury reacts with either piperidine or chlorodialkylamines to give "tri!nitromethyl#mercuric amides in very high yields "Equation "06## ð56IZV1697Ł[

(17)Hg[C(NO2)3]2 + R2NXether

0 °C, 3 hR2NHgC(NO2)3

R2NX = N-chloropiperidine, 92%; N-chlorodimethylamine, 91%; piperidine (2 equiv.), 30%

The adduct of 1\1?!azobis"isobutyronitrile# with Hg"C"NO1#2#1 reacts as a mercurating agenttowards 1\3!dioxypentane to a}ord 2!"1\3!dioxopentyl#trinitromethylmercury "Equation "07##ð66IZV0452Ł[

(18)Hg[C(NO2)3]2 + MeCOCH2COMeAIBN

(MeCO)2CHHgC(NO2)3

Insertion of alkenes into the C0Hg bond of bis"trinitromethyl#mercury has been studied[Cyclohexene undergoes trans!addition whilst norbornene gives an exo!cis product\ as found in thecase of more classical mercuration reactions "Equation "08## ð57IZV0527Ł[

(19)Hg[C(NO2)3]2 + MeNO2

20 °C, 10 d42% C(NO2)3

HgC(NO2)3

258Three Group 04 Elements and a Metalloid

A similar addition to 2\4!dinitrocyclopentene has been reported ð69IZV1097Ł but the stereo!chemistry of the addition was not de_ned[

The reaction with allyltrimethylsilane is relatively complex] after the _rst mercuration\ the elim!ination of trimethylsilane generates a new site of unsaturation which undergoes a second additionof the organomercury reagent "Equation "19## ð62RZC0132Ł[

(20)2Hg[C(NO2)3]2 + TMS(O2N)3CHg HgC(NO2)3

C(NO2)3(O2N)3C

62%

Several metal salts of trinitromethane\ M¦−C"NO1#2\ have been prepared] their stability dependsquite strongly upon the counterion[ Alkaline metals and ammonium salts are reported to decomposeexothermically\ without explosion\ upon heating ð66IZV0854Ł[ The speci_c impulse properties ofcompounds such as Me1AlC"NO1#2 and LiC"NO1#2 have been measured ð60USP2451298Ł\ and Me2SiC"NO1#2 decomposes violently ð82TL0748Ł[ The alkali metal salts "K\ Rb\ Cs# and ammoniumcompounds of the trinitromethanide anion may be prepared by reaction of trinitromethane withthe corresponding hydroxide ð66IZV0854Ł\ whilst the Al\ Mg\ B\ Be and Li salts were prepared fromthe metal alkyls and a stoichiometric amount of HC"NO1#2 or BrC"NO1#2 in pentane ð60USP2451298Ł[The silver salt may be prepared in situ from HC"NO1#2 and silver oxide in MeCN ð52T"S#066Ł[It reacts with chlorodiphenylstibine to a}ord diphenyl"trinitromethyl#stibine "64Ð79) yield#\ whichis also accessible less e.ciently in 29Ð49) yield from the potassium salt "Equation "10## ð74IZV328Ł[

(21)MC(NO2)3 + Ph2SbClCH2Cl2

20 °C, 4 hPh2SbC(NO2)3

M = K, Ag

Finally\ two potassium salts of a "dinitromethyl#hydrazine\ K¦−C"NO1#1N"COR#NHCOR\ havebeen very brie~y described\ but no synthetic details were given ð64IZV1727Ł[

5[01[1[0[1 Three phosphorus functions

A wide variety of methanes having a lithium or sodium atom and three phosphorus substituentshave been prepared as anionic tripod ligands for coordination chemistry[ Variants having tri! andpentavalent phosphorus atoms are known\ and syntheses have been devised which permit thetargeting of ligands containing any desired combination of oxygen and sulfur!bound phosphorusatoms[ The synthesis of the alkali!metal derivatives has been accomplished by proton abstractionfrom the parent methane\ HtrisXYZ\ with various reagents[ Selected examples are given in Table 5"Equation "11##[ The lithium salts containing phosphorus"V# atoms are fairly air stable and can bestored for several months without change[ An x!ray crystal structure determination of LiC"PMe1#2shows that the lithium atom is bound to both of the phosphorus lone pairs and to the carbon atomð73CC458Ł[ This implies that the charge is delocalized over the phosphorus and the carbon atomsand indicates that reactivity towards electrophiles is complex[

(22)R1M

R2(X)P

P(Y)R2

P(Z)R2

M

P(X)R2

P(Z)R2

P(Y)R2

Table 5 Metalation reactions of HtrisXYZ[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

YieldHTrisXYZ Rea`ents and conditions ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐHCðP"O#Ph1Ł2 LiOMe\ CH1Cl1\ 14>C\ 4 h 67 75IC1588HCðP"O#Ph1Ł2 NaH\ THF 89JA6873HCðP"O#Ph1Ł1ðP"S#Ph1Ł LiOMe\ CH1Cl1\ 14>C\ 4 h 71 75IC1588HCðP"O#Ph1ŁðP"S#Ph1Ł1 LiOMe\ CH1Cl1\ 14>C\ 4 h 62 75IC1588HCðP"S#Ph1Ł2 LiOMe\ CH1Cl1\ 14>C\ 4 h 61 75IC1588\ 71CC829HCðP"S#Me1Ł2 ButLi\ THF\ −19:14>C\ 4 h 65 71CB707HC"PMe1#2 ButLi\ pentane\ 14>C\ 09 h 62 68ZN"B#0067HCðPPh1Ł2 LiOMe\ MeOH ×55 75IC1588*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ


The analogous Hg {{trisS2|| derivatives are prepared directly by reaction of the parent methane{{HtrisS2|| with the corresponding metal halides in ethanol solution] the cadmium analogues maybe prepared similarly in the presence of a mild base such as triethylamine "Equation "12## ð74IC1778Ł[In the solid state\ the complexes are bound through the sulfur atoms\ but there is some circumstantialevidence for coordination to carbon in solution[

(23)MX2

R2(Y)P

P(Y)R2

P(Y)R2

XM

P(Y)R2

P(Y)R2

P(Y)R2

M 3P(Y)R2 X Yield (%)Hg 3P(S)Ph2 Cl 92Hg P(S)Ph2[P(S)Me2]2 Cl 85Cd 3P(S)Ph2 Cl 94Cd P(S)Ph2[P(S)Me2]2 Cl 56

5[01[2 METHANES BEARING TWO GROUP 04 ELEMENTS AND METALLOID AND:ORMETAL FUNCTIONS

5[01[2[0 Two Similar Group 04 Elements

5[01[2[0[0 Two nitrogen functions

There appears to be only one compound of this general class which has featured in the literature[Lithiation of N!"benzotriazol!0!ylmethyl# pyrrole with n!butyllithium and subsequent addition ofchlorotrimethylsilane gave a mixture of products which included the bis"trimethylsilyl# derivative"Equation "13## ð78JHC718Ł[ The reported yield was relatively low "25)#\ but it appears that themethod could be synthetically useful if two equivalents of n!butyllithium and chlorotrimethylsilanewere used[

i, BunLi

ii, TMS-ClN

N NN

N

N NN

TMS

TMS

(24)

5[01[2[0[1 Two phosphorus functions

A few compounds in which a carbon atom bears two phosphorus and two silicon functions havebeen described[ All have trimethylsilyl substituents\ but the phosphorus moieties may be eitherphosphines "PR1#\ phosphonium salts "PR2

¦#\ phosphorus ylides "1PR1# or phosphaalkenes"R1C1P#[

The earliest report of such a compound concerned a bisphosphonium salt\ prepared by addition oftwo equivalents of chlorotrimethylsilane to a symmetrical dimethyltetraphenylcarbo!diphosphorane"Equation "14##[ This phosphonium salt is relatively unstable and decomposes within a few minutesð65ZN"B#610Ł[

TMS-Cl

C6H6

Ph2MeP • PMePh2 (25)Ph2MeP PMePh2

TMS TMS

+ +

2Cl–

A second example involves the addition of a chlorophosphaalkene to a phenyl! or alkylnyllithiumreagent\ which gives a phosphinomethyl substituted phosphaalkene[ It is proposed that the reaction

260Two Group 04 Elements and Metalloid

proceeds through the intermediacy of a lithium bis"trimethylsilyl# phosphinomethanide which reactswith a second equivalent of the chlorophosphaalkene "Scheme 05# ð75CB1598Ł[

2RLi

ether, –78 °C, 2 h

ClPTMS

TMS

ether, –78 °C, 2 hClP

TMS

TMS

TMS

TMS

Li

R2P

TMS

TMS

P

R2P

TMS

TMS

Scheme 16

R = TMSC≡C, 70%; PhC≡C, 60%; Ph, 54%

In the case where R�TMS!C2C\ a subsequent pyrolysis gave a bis"trimethylsilyl#!substituteddiphosphirane in 31) yield] this reaction proceeds through an intramolecular ð1¦1Ł cycloadditioninvolving the P0C double bond and one of the C0C triple bonds\ and a subsequent rearrangement"Equation "15## ð75CB1598Ł[

∆

toluene, 100 °C, 20 min

TMS

TMS

P

(TMSC≡C)2P

TMS

TMSP

PTMS

TMS

•

TMS

TMS

TMSTMS

(26)

The last compound is a phosphino!phosphorane derivative\ which is prepared in poor yield bymeans of a zirconium!mediated synthesis "Scheme 06# ð82OM1646Ł[

LiC(PMe)2(TMS)2

ether, –78/25 °C(C5H5)2ZrCl2

(C5H5)2ClZr

PTMS

TMS

Me Me

LiC(PMe)2(TMS)2

ether, –78/25 °C, 18 h

P

PMe2

TMS

TMS

TMS

TMS

Scheme 17

Compounds containing two phosphorus\ a silicon and a lithium function as substituents at thecentral carbon are also known[ Bis"phosphino#methanides and a bis"thiophosphinyl#methanidehave been prepared by metalation with n!butyllithium of the corresponding trisubstituted methanes"Equation "16## ð77ZN"B#0305\ 81CB0222Ł[

BunLiMe2(X)P

P(X)Me2

TMS

Li

P(X)Me2

TMS

P(X)Me2 (27)

X = lone pair, hexane, 30 °C, several days, 99%X = S, toluene, –78/25 °C, 12 h, 95%

The mercuration of methylenediphosphonate compounds which contain an acidic hydrogen isknown[ Reaction of mercuric acetate with a methylenediphosphonate in re~uxing tetrahydrofuranprovokes bis"mercuration# at the carbon atom with the loss of acetic acid[ The product undergoesredistribution reactions with other organomercurials "Scheme 07# ð62JOM"48#120Ł

X = Br, THF, 17 h, 73%; Cl, THF, ∆, 26 h, 72%; Ph, EtOH, ∆, 60%

Hg(OAc)2

THF, 70 °C

P(O)(OEt)2

P(O)(OEt)2

AcOHg

AcOHg

P(O)(OEt)2

P(O)(OEt)2

XHg

XHg

(EtO)2(O)P P(O)(OEt)2

Scheme 18

HgX2

Methylenediphosphines react in a similar fashion with a mixture of mercuric acetate and theDMSO adduct of mercuric tri~ate\ Hg"DMSO#5"OSO1CF2#1[ The _rst\ monomercurated\ productreacts further with mercuric acetate to give an unstable dimercurated compound which could not


be isolated "Equation "17## ð73OM0805Ł[ It should be noted that such a mercuration reaction failedfor a related tris"phosphino#methane ð75JOM"290#158Ł[

Hg(OAc)2, Hg(DMSO)6(OTf)2

MeOH, 25 °CPh2P PPh2

2+

2TfO–AcOHgPh2P

HgOAc

PPh2HgOAc

HgOAc (28)

5[01[3 METHANES BEARING ONE GROUP 04 ELEMENT AND METALLOID AND:ORMETAL FUNCTIONS

5[01[3[0 Nitrogen Functions

A computer search of the Chemical Abstract Data Base has not revealed any compound belongingto this subgroup[

5[01[3[1 Phosphorus Functions

5[01[3[1[0 One phosphorus and three silicon functions

The most important compounds bearing one phosphorus and three silicon functions are methaneswhich carry one phosphorus and three trimethylsilyl functions[ Many of these compounds may beprepared directly from PCl2\ or the corresponding chlorophosphine\ and tris"trimethyl!silyl#methyllithium "Equation "18## according to the conditions outlined in Table 6[ The experimentalprocedure employed for this transformation appear to be quite critical to the success of the reaction[A similar series of reactions which involve the related reagent "PhMe1Si#2CLi has been described]the reaction with PCl2 proceeds in 50) yield ð78JOM"255#28Ł[

(29)Li

TMS

TMS

TMSR2PCl

PR2

TMS

TMS

TMS

Table 6 Reactions of tris"trimethylsilyl#methyllithium with chlorophosphanes[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

YieldR1PX Conditions ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐPCl2 THF\ 9>C\ 1 h 54 79ZC042

THF!ether\ 19>C\ 1 h 54 78JOM"255#28THF\ 9:14>C\ 1 h 56 89IS124

MePCl1\ ButPCl1\ Et2CPCl1\ PhPCl1\ THF\ 55>C\ 7 h ×69 79ZC308\ 70ZAAC"362#74TMSCH1PCl1\ 1\3\5!Me2!C5H1PCl1

Ph1PCl ether\ 39>C\ 1 h 37 72JCS"D#894*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Treatment of tris"trimethylsilyl#methyllithium with "trimethylsilyl#aminodi~uorophosphinescauses the replacement of one of the ~uorine atoms by tris"trimethylsilyl#methyl group[ Smallquantities of tris"trimethylsilyl#methyldi~uorophosphine are also formed[ Upon heating\ these com!pounds are easily transformed in phosphaalkenes through elimination of ~uorotrimethylsilane\presumably because of sterical pressure "Scheme 08# ð73ZN"B#0499Ł[

Li

TMS

TMS

TMSP

TMS

TMS

TMS+ NF2P

TMS

R

N

F

TMS

R P

TMS

TMS

N

R

TMS∆

R = adamantyl, 46%; But, 79%; mesityl, 60%; TMS, 48%

Scheme 19

262One Group 04 Element and Metalloid

The reactivity of tris"trimethylsilyl#methyllithium towards electrophiles is complicated by ex!change reactions[ Thus\ this lithium reagent reacts with phosphorus tribromide to give principallybromotris"trimethylsilyl#methane\ and only traces of dibromo"tris"trimethylsilyl#methyl#phosphine[If required\ dibromo"tris"trimethylsilyl#methyl#phosphine may be prepared e.ciently by reactionof BBr2 with the corresponding dichloro derivative[ The compound "TMS#2CPCl1 has also beenused for the synthesis of "TMS#2CPH1\ "TMS#2CPH1 =BH2 and "TMS#2CP"O#Cl1 by reaction withLiAlH3\ NaBH3 and AgNO2 respectively ð78JOM"255#28Ł[

Reduction of "TMS#2CPCl1 with ButLi\ sodium naphthalenide or "TMS#2CLi gives the bis"tri!s"trimethylsilyl#methyl#diphosphene "Equation "29## ð71TL3830\ 71JA4719Ł[

PCl2TMS

TMS

TMS P

TMS

TMS

TMS P

TMS

TMS

TMS (30)

A similar interaction of "TMS#2CPCl1 with lithium trimethylsilylphosphides leads to silyl!sub!stituted diphosphines[ The triphenylsilyl derivative is stable but its trimethylsilyl analogue evolvesto give a compound having a tetraphosphabicyclobutane structure "Scheme 19# ð78OM1389Ł[

PCl2TMS

TMS

TMS P

TMS

TMS

TMS PSiR3

LiP(TMS)SiR3

ether, –70/25 °C

R = Me PP

PP

TMS

TMS

TMS

TMS

TMS

TMS

R = Me, unstable; Ph, 61%

Scheme 20

The diphosphene "TMS#2CP1PC"TMS#2 undergoes further transformations at the phosphorusÐphosphorus double bond[ These include ozonolysis ð73CC0511Ł\ ð1¦0Ł cycloadditions with carbenesð78CC482Ł or isonitriles ð81ZAAC"506#42Ł and reactions with HCl ð75JCS"D#0790Ł] each of thesetransformations leaves the tetrasubstituted carbon atom unchanged[

A reaction producing a carbon atom bearing one phosphorus and three silicon functions throughaddition of a phosphorusÐoxygen bond to a transient silaethene is known[ The additionof "PhO#1P"O#OSiMe2 to the silicon carbon double bond is favored over a competing insertion ofthe C1Si function into the O0Si linkage "Scheme 10# ð70CB2494Ł[

Si

TMS

TMS

BrBunLi

ether, –78 °C

TMS-OP(O)(OPh)2

ether, –78/25 °C82%

Me2Si

TMS

TMS(PhO)2(O)P

Me

Me

SiMe2(O-TMS)

TMS

TMS

(PhO)2(O)P

Scheme 21

Finally\ the reaction of iodotrimethylsilane with bis"trimethylsilyl#methylene trimethylphos!phorane leads to an iodophosphonium compound in 74) yield "Equation "20## ð69CB2337Ł[

Me3P

TMS

TMS

+ TMS-I25 °C, 4 d

85%

Me3P

TMS

TMS

TMS+

I– (31)

5[01[3[1[1 One phosphorus\ one metal and two silicon functions

Most of the compounds which fall within this section are organolithium reagents\ but a numberof organoaluminum compounds are also known[

Bis"trimethylsilyl#phosphinomethanes\ R1PCH"TMS#1\ may be metalated by BunLi to give thecorresponding organolithium reagents "Equation "21## "R�Ph ð73CB1952Ł^ R�Me ð77ZN"B#0305Ł#[A crystal structure determination of bis"trimethylsilyl#dimethylphosphinylmethyllithium shows adimeric structure for its TMEDA adduct[ In accordance with the ambidentate reactivity which thesecompounds show towards electrophiles\ each lithium atom is bound to carbon and to phosphorusð73CB1952Ł[


(32)TMS

TMS

BunLiR2P

TMS

TMS

LiR2P

R = Me, TMEDA, hexane, 25 °C, 7 d, 76%R = Ph, DME, hexane, 25 °C, 12 h, 95%

Bis"trimethylsilyl#methylphosphonates and !phosphine oxides are also metalated by LDA andmethyllithium\ respectively[ Yields are good to excellent "Equation "22## ð73JOC4976\ 76JOM"212#024Ł[The metalation of dialkylmethyl phosphonates by three equivalents of LDA and subsequent treat!ment with two equivalents of chlorotrimethylsilane also provides a simple and e.cient route to thesame carbanions "X�MeO\ 57)^ EtO\ 74)^ PriO\ 14)# ð76JOM"212#024Ł[

(33)TMS

TMS

RLiX2(O)P

TMS

TMS

LiX2(O)P

X RLi Conditions Yield (%)EtO LDA THF, –50 °C >91MeO LDA THF, –50 °C >92Ph MeLi 0 °C

Lithium to aluminum exchange reactions of bis"trimethylsilyl#dimethylphosphinomethyllithiumhave been reported[ The reactions are generally complex and give cyclic structures[ A number ofexamples are given in Scheme 11 ð89"CC#0510\ 80"CC#355\ 80OM1773Ł[

TMS

TMS

Me2P Li(TMEDA)Me2P

SiPMe2

AlTMS

TMSClMe

Me MeTMS

TMS

TMS

pentane/toluene

–78/25 °C84%

Me2P Li(TMEDA) + Me2AlCl

Me2Al

PMe2

Li(TMEDA)Cl

TMS

TMS

pentane, –78/25 °C80%

+ AlCl3

Scheme 22

5[01[3[2 Arsenic or Antimony Functions

Tris"trimethylsilyl#methyldichloroarsane\ which forms the starting point for the preparation ofeach arsenic containing compound of this general type\ may be prepared from AsCl2 and "TMS#2CLi"Equation "23## ð72TL1658Ł[ The conditions employed were similar to those used for the preparationof its phosphorus analogue ð79ZC042Ł[

Li

TMS

TMS

TMS + AsCl3 AsCl2TMS

TMS

TMS (34)

The chlorine atoms of "TMS#2CAsCl1 may be substituted either by a methoxyl group or by anallenyl function[ Subsequent transformations give a dimer which results from the head!to!taildimerization of the As0C double bonds of two 0!arsabutatriene units "Scheme 12# ð89TL5220Ł[

Scheme 23

•

Cl

As

TMS Ph

Ph NaOH

MeOH82%

•

OMe

As

Ph

Ph ButLi

–78 °C47%

As

As••

Ph

Ph Ph

Ph

TMS TMSTMS

TMS TMSTMS

TMS

TMS

TMS

TMS

TMS

TMS

264One Group 04 Element and Metalloid

Reduction of "TMS#2CAsCl1 by t!butyllithium ð72TL1658Ł or organometallic complexesð75ZN"B#080Ł leads to a tris"trimethylsilyl#methyl!substituted diarsene\ whose crystal structureð74JCS"D#272Ł\ electrochemical properties ð76JCS"D#138Ł\ oligomerization reactions ð73JCR"S#163Ł\and sulfuration ð72TL1658Ł have been described "Equation "24##[

AsCl2TMS

TMS

TMS As

TMS

TMS

TMS

TMS

TMS

TMSAs (35)

Reduction of a mixture of "TMS#2CAsCl1 and "TMS#2CPCl1 by t!butyllithium gave the phos!phaarsene "TMS#2CAs1PC"TMS#2\ and the symmetrical diarsene and diphosphene in unspeci_edyield ð72TL2514Ł[

Finally\ the synthesis of the highly photosensitive "TMS#2CSbCl1 from "TMS#2CLi and SbCl2 hasbeen described brie~y\ but no experimental details were given ð74JA7100Ł[

5[01[4 ACKNOWLEDGEMENTS

In collecting the literature\ the authors have bene_ted greatly from collaboration with MsFrancžoise Girard\ who is gratefully acknowledged[


6.13Functions Containing at LeastOne Metalloid (Si, Ge or B)and No Halogen, Chalcogen orGroup 15 Element; Also FunctionsContaining Four MetalsPAUL D. LICKISSImperial College of Science, Technology and Medicine, London,UK

5[02[0 METHANES CONTAINING AT LEAST ONE METALLOID "AND NO HALOGEN\CHALCOGEN OR GROUP 04 ELEMENT# 267

5[02[0[0 Methanes Bearin` Four Metalloid Functions 2675[02[0[0[0 Four similar metalloid functions 2675[02[0[0[1 Three similar and one different metalloid function 2765[02[0[0[2 Two similar and two different metalloid functions 277

5[02[0[1 Methanes Bearin` Three Metalloid Functions and a Metal Function 2895[02[0[1[0 Three similar metalloid functions 2895[02[0[1[1 Other mixed metalloid functions 286

5[02[0[2 Methanes Bearin` Two Metalloid and Two Metal Functions 2875[02[0[2[0 Two Si and two metal functions 2875[02[0[2[1 Two Ge and two metal functions 3995[02[0[2[2 Two B and two metal functions 3995[02[0[2[3 Other combinations of two metalloids and two metal functions 390

5[02[0[3 Methanes Bearin` One Metalloid and Three Metal Functions 3905[02[0[3[0 One Si and three metal functions 3905[02[0[3[1 One Ge and three metal functions 3935[02[0[3[2 One B and three metal functions 393

5[02[1 METHANES BEARING FOUR METAL FUNCTIONS 393

5[02[1[0 Methanes Bearin` Four Similar Metals 3935[02[1[1 Methanes Bearin` Three Similar and One Different Metal Function 3945[02[1[2 Methanes Bearin` Two Similar and Two Different Metal Functions 3945[02[1[3 Methanes Bearin` Four Different Metal Functions 394

5[02[2 METHANES BEARING MORE THAN FOUR METALLOID OR METAL FUNCTIONS 395

266


5[02[0 METHANES CONTAINING AT LEAST ONE METALLOID "AND NO HALOGEN\CHALCOGEN OR GROUP 04 ELEMENT#

There are a huge number of potential substitution patterns at tetravalent carbon covered by thetitle of this section[ Besides the elements speci_cally excluded in the title of the section and thelanthanides\ the actinides and Fr\ Ra and Tc*there are 36 elements which could be considered assubstituents to be covered in the section[ There are 129299 possible combinations""3¦n−0#;:3;"n−0#; for n�36# of these 36 elements at four coordinate carbons "not including afurther 067254 optical isomers generated by having four di}erent elements as substituents#[ About59 i[e[\ 9[915) are discussed below[ Thus it is clear that there is still enormous scope for the syntheticchemist in the preparation of such organometallic compounds[ It has been impossible to carry outa comprehensive search of the literature for all the possible functions covered under this heading\but it is hoped that the majority of important functions have been found[ In some cases\ carbonsubstituted by four metals may better be regarded as an interstitial carbide and more the provinceof the inorganic chemist^ such species have been omitted[

5[02[0[0 Methanes Bearing Four Metalloid Functions

There are a large number of compounds known containing a carbon substituted by four siliconfunctions^ such compounds may be prepared in a wide variety of ways[ In view of the number oftetrasilylmethanes known\ surprisingly\ there seems to be no analogous germanium substitutedspecies\ although this is presumably due to a lack of synthetic e}ort rather than any inherentinstability[ A relatively small number of methanes substituted by four boron functions have beenprepared\ and there is also a range of compounds containing either a variety of metalloid functionsor mixed metalloid and metal functions[

5[02[0[0[0 Four similar metalloid functions

"i# Four Si functions

"a# Tetrasilylmethanes from in situ couplin` reactions[ A range of compounds containing the Si3Cfunction has been prepared by in situ coupling reactions in which most\ if not all of the four Si0Cbonds are formed in the same reaction[ Simple compounds of the type "R0

1R1Si#3C can be made bycoupling reactions using di}erent metals and di}erent halomethanes according to the generalreaction "Equation "0##[ The range of precursors used for this type of synthesis and the productsobtained are given in Table 0[

R12R2SiCl + metal + tetrahalomethane (R1

2R2Si)4C + metal halide (1)

Table 0 Reagents used in and products formed from in situ coupling reactions[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

YieldChlorosilane Metal Halomethane Si3C Product ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐTMSCl Mg CBr3 "TMS#3C 17 53JOC842TMSCl Mg CBrCl2 "TMS#3C 19 53JOC842TMSCl Mg CBr1Cl1 "TMS#3C 29 53JOC842TMSCl Li CBr3 "TMS#3C 17 54JOM"3#87TMSCl Li CCl3 "TMS#3C 22Ð55[4 53MI 502!90\ 54JOM"3#87Me1SiHCl Mg CBr3 "Me1HSi#3C 44Ð59 53JOC842\ 74JOM"183#294PhMe1SiCl Mg CCl3 "PhMe1Si#3C 00 69JOM"13#78PhH1SiCl Mg CBr3 "PhH1Si#3C ca[ 34 89AG"E#190MeSiCl2 Mg CBr3 "MeCl1Si#3C 75ZN"B#0416SiCl3 Mg CBr3 "Cl2Si#3C 75ZN"B#0416*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

The in situ tetrasilylation reactions may be written as simple sequential metallationÐsilylationsteps\ but actually the mechanism is likely to be rather more complicated as rapid ligand exchangebetween TMS\ Br and Li has been shown to occur even at low temperatures in the TMSCl:CBr3:Lisystem ð69TL3582Ł[ Sequential lithiationÐsilylation reactions can also be carried out using CH1Cl1


and BunLi in a 0 ] 3[4 ratio\ quenching with TMSCl to give "TMS#3C in 25) yield ð61JOC1551Ł[ Thecoupling of CLi3\ either as a solid or in solution\ with TMSCl gives a 4) yield of "TMS#3C ð61CC0967\73AG"E#884Ł[ The tetrasilylation of CCl3 can also be achieved electrochemically\ silylation usingTMSCl and an aluminium anode giving "TMS#3C in 59) yield along with di! and trisilylatedproducts ð77JOM"247#20Ł[ The coupling reaction between "0# and CCl3 in the presence of lithium"Equation "1## a}ords the heptasilað3[3[3Łpropellane "1#^ again all four Si0C bonds are formed ina single reaction[ This reaction presumably proceeds in a stepwise manner with sequential formationof chloromethyl lithium reagents which react in turn with the four Si0Br groups in the organosiliconprecursor[ However\ there may be rapid exchanges between Li\ Cl\ Br and silyl groups also takingplace as mentioned above for the TMSCl:CBr3:Li system[ Perhaps not surprisingly for such acomplicated reaction\ the yield is low "4)# ð65ZAAC"308#1Ł[

Si

SiMe2

SiMe2Me2Si

Me2SiSiMe2

Me2Si Si

SiMe2

SiMe2Me2Si

SiMe2

SiMe2

Me2SiBr

BrBr

Br

+ CCl4 + 8Li (2)

+ 8LiCl

(1) (2)

The phenylsilylmethane "PhH1Si#3C "see Table 0 for its synthesis# is of interest as it is the precursorto "BrH1Si#3C\ via Si0Ph bond cleavage by HBr\ which may then be reduced under phase transferconditions using LiAlH3 to give "H2Si#3C\ the Si:C inverse of the well!known Me3Si ð89AG"E#190Ł[This silane cannot be prepared from "Cl2Si#3C as both trisilylmethyl and Cl2Si− anions are goodleaving groups and attempted reductions lead to Si0C bond cleavage[ Interest in "H2Si#3C andother H2Si substituted methanes stems from their potential as chemical vapour deposition precursorsto thin _lms of amorphous hydrogenated silicon carbide ð81JOM"318#0Ł[

"b# Formation by reaction between a trisilyllithiomethane and a halo! or pseudohalosilane[ Thereactions between tris"trimethylsilylmethyl#lithium "for its synthesis see 5[02[0[1[0 "i# "a## and halo!or pseudohalosilanes have been used to prepare a large number of tetrasilylmethanes via the simplecoupling reaction outlined in Equation "2#[

(TMS)3CLi + R1R2R3SiX (3)(TMS)3CSiR1R2R3 + LiX

The range and yields of compounds prepared by the method given in Equation "2# are given inTable 1[ The formation of such compounds is greatly a}ected by steric factors^ for example\ additionof more than one equiv[ of the lithium reagent "TMS#2CLi "{TsiLi|# to a di!\ tri! or tetrahalosilanedoes not lead to the substitution of more than one Tsi group for a halide^ i[e[\ it does not seem tobe possible to attach more than one Tsi group to any one Si atom[ It should also be noted that\ forthe synthesis of the most sterically hindered compounds\ improved yields are obtained if silyl~uorides are used rather than silyl chlorides "presumably again for steric reasons#^ for example\TsiLi reacts with Ph1SiCl1 and with Ph1SiF1 to give TsiSiPh1X products in 7 and 65) yield\respectively^ see Table 1[

A variety of other trisilylmethyllithium reagents that are less symmetrical than TsiLi have alsobeen prepared "see 5[02[0[1[0["i#"a##\ and they react in a similar way with halosilanes to givetetrasilylmethanes "Table 2#[ The variety of functional groups that may be present in the tri!silylmethyllithium reagents is greater than might be expected considering the reactivity of normalalkyllithium reagents with functional organosilanes[ This unusual compatibility of a functionalgroup on silicon and an alkyllithium function is presumably due to the fact that the reagents areoften prepared at very low temperatures and also because steric constraints are likely to hinder theattack of one bulky molecule on another[

Tetrasilylmethane products may also be formed in the reactions of disilylmethane derivativeswith lithium or organolithium reagents[ The reaction of "TMS#1CCl1 with four equivalents of lithiumin the presence of PriSiF2 at room temperature gives "TMS#1C"SiPriF1#1 in 37) yield ð74JOM"180#166Ł[Alternatively\ "TMS#1CLi1 can be prepared "see 5[02[0[2[0# at room temperature and it reacts withTMSCl to give "TMS#3C in 20) yield ð77TL4126Ł[ The reactions of "TMS#1CClLi with halosilanesoften gives mixtures containing tetrasilylmethane products as well as the expected trisilylmethanes"Equation "3## ð73ZAAC"409#058Ł[


Table 1 Products obtained from the reaction between "TMS#2CLi "TsiLi# and halo! or pseudohalosilanesR0R1R2SiX[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐYield

RR0R1SiX Product ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐTMSCl TsiTMS 46Ð74 69JOM"13#418\ 66JOM"031#28\ 81OM1827TMSCN TsiTMS 67 75JOC2434Me1Si"N2#1 TsiSiMe1N2 71AG"E#332SiH1Cl1 TsiSiH1Cl 82TH50290MeSiHCl1 TsiSiMeHCl 08Ð44 69JOM"13#418\ 68JCR"S#01MeSiF2 TsiSiMeF1 58 74ZN"B#0912SiF3 TsiSiF2 57Ð63 73ZAAC"409#064\ 75JOM"298#136ButSiF2 TsiSi"But#F1 41Ð60 73ZAAC"409#064\ 75JOM"298#136PriSiF2 TsiSi"Pri#F1 56 76JOM"212#0Me1SiF1 TsiSiMe1F 54 76JOM"212#0Et1SiF1 TsiSiEt1F 39 69JOM"13#418Pri

1SiF1 TsiSi"Pri#1F 51 76JOM"212#0PhSiF2 TsiSiPhF1 56 73ZAAC"409#064Me1SiHCl TsiSiMe1H 76 69JOM"13#418SiCl3 TsiSiCl2 67 69JOM"13#418Me1SiCl"OMe# TsiSiMe1OMe 59 69JOM"13#418Si"OPri#Cl2 TsiSiCl1"OPri# 39 69JOM"13#418Me1SiCl1 TsiSiMe1Cl 71 69JOM"13#418Et1SiCl1 TsiSiEt1Cl 37 69JOM"13#418EtMeSiHCl TsiSiEtMeH 59 69JOM"13#418PhSiCl2 TsiSiPhCl1 64 69JOM"13#418PhSiHCl1 TsiSiPhHCl 06 69JOM"13#418Ph1SiCl1 TsiSiPh1Cl 7 69JOM"13#418Ph1SiF1 TsiSiPh1F 65 69JOM"13#418PhMeSiHCl TsiSiPhMeH 79 69JOM"13#418PhMeSiF1 TsiSiPhMeF 63 69JOM"13#418Ph1SiF"OMe# TsiSiPh1OMe 8 69JOM"13#418PhMe1SiF TsiSiMe1Ph 02 70JOM"110#02Me1"CH11CH#SiCl TsiSiMe1"CH1CH1# 44 74JOM"180#14Me1"CH11CHCH1#SiCl TsiSiMe1"CH1CH1CH1# 27 74JOM"180#14Me1"PhC2C#SiF TsiSiMe1"C2CPh# 05 74JOM"180#14Me1"PhCH1#SiF TsiSiMe1"CH1Ph# 19 74JOM"180#14"CH11CH#1SiCl1 TsiSi"CH1CH1#1Cl 40 75JCS"P1#0178"Cl2Si#1O "TsiSiCl1#1O 04[4 89JOM"287#48*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐTsi�"Me2Si#2C[

Cl

LiTMS

TMS SiR1R2F

SiR1R2F(4)

TMS

TMS + R1R2SiF2 trisilyl products +

R1 = R2 = F, 41%

R1 = F, R2 = Me, 36%

R1 = Me, R2 = Ph, 36%

R1 = F, R2 = Ph, 29%

R1 = F, R2 = But, 71%

"c# Formation via addition reactions of silenes[ Cyclic compounds containing an Si3C function inthe ring are formed in similar reactions to those shown in Equation "3#^ for example\ in Scheme 0the initial metallation gives rise to a lithium reagent that can readily eliminate a salt to give ahighly reactive silene "Si1C containing species# which rapidly dimerises in a head!to!tail manner togive "2# in 31) yield ð73ZAAC"409#058Ł[ Similarly\ the reaction between "TMS#1CBrLi and Me1SiCl1gives a 29) yield of "3#\ presumably via initial formation of "TMS#1CBr"SiMe1Cl#\ which undergoesLi:Br exchange with the original lithium reagent to give "TMS#1CLi"SiMe1Cl#\ which then eliminatesLiCl[ Finally\ the silene "TMS#1C1SiMe1 which is formed\ dimerises ð65JOM"005#146Ł[

A range of trisilylmethyllithium species "TMS#1CLi"SiMe1X# "X�F\ Cl\ Br\ I\ PhS\ Ts\ TsO\MsO\ Ph1PO1\ Ph1PO2\ Ph1PO3# have been prepared "see 5[02[0[1[0["i#"a# for details# which\ in theabsence of any trapping reagent\ "cf[ reactions in Table 2# eliminate LiX at various temperaturesranging from about −099>C to above room temperature to give the silene "TMS#1C1SiMe1 whichrapidly dimerises to give the disilacyclobutane "3# ð70CB1976\ 70CB2494\ 70CB2407Ł[ "For reactions


Table 2 Tetrasilylmethanes from the reaction of miscellaneous trisilyllithiomethanes with halosilanes[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

YieldLithiomethane Halosilane Product ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ"PhMe1Si#2CLi SiCl3 "PhMe1Si#2CSiCl2 81JOM"316#8"PhMe1Si#2CLi SiH1Cl1 "PhMe1Si#2CSiH1Cl 48 82TH50290"PhMe1Si#2CLi MeSiHCl1 "PhMe1Si#2CSiMeHCl 72 74JCS"P1#618"PhMe1Si#2CLi Me1SiHCl "PhMe1Si#2CSiMe1H 64 74JCS"P1#618"p!MeC5H3SiMe1#2CLi Me1SiHCl "p!MeC5H3SiMe1#2CSiMe1H 83JOM"355#24"MeOMe1Si#2CLi Me1SiHCl "MeOMe1Si#2CSiMe1H 78 75CC0932\

81JCS"D#0904"MeOMe1Si#2CLi Me1SiCl1 "MeOMe1Si#2CSiMe1Cl 33 81JCS"D#0904"MeOMe1Si#2CLi Ph1SiClH "MeOMe1Si#2CSiPh1H 54 81JCS"D#0904R1C"SiMe1Ph#Lia Me1SiHCl R1C"SiMe1Ph#"SiMe1H# 51 82JCS"P1#48\

83JOM"355#24R1C"SiMe1Ph#Li Et1SiHCl R1C"SiMe1Ph#"SiEt1H# 43 82JCS"P1#48R1C"SiMe1Ph#Li Et1SiF1 R1C"SiMe1Ph#"SiEt1F# 29 82JCS"P1#48R1C"SiMe1Ph#Li Et1SiCl1 R1C"SiMe1Ph#"SiEt1Cl# 8[4 82JCS"P1#48R1C"SiMe1C5H3Y#Lib Me1SiHCl R1C"SiMe1C5H3Y#"SiMe1H# 83JOM"355#24R1C"SiMe1OMe#Li TMSCl R2C"SiMe1OMe# 70CB1976R1C"SiMe1OMe#Li Me1SiHCl R1C"SiMe1OMe#"SiMe1H# 51 75JCS"P1#0252R1C"SiMe1OMe#Li Me1SiCl1 R1C"SiMe1OMe#"SiMe1Cl# 34 74JCS"P1#0576R1C"SiMe1OMe#Li Ph1SiHCl R1C"SiMe1OMe#"SiPh1H# 30 76JCS"P1#780RC"SiMe1OMe#1Li Me1SiCl1 RC"SiMe1OMe#1"SiMe1Cl# 81JCS"D#0904R1C"SiMe1H#Li Et1SiCl1 R1C"SiMe1H#"SiEt1Cl# 71 82JCS"P1#280R1C"SiMe1H#Li Me1SiCl1 R1C"SiMe1H#"SiMe1Cl# 64 82JOM"340#34R1C"SiMe1Cl#Li Me1SiCl1 R1C"SiMe1Cl#1 20 65JOM"005#146R1C"SiMe1Bun#Li TMSCl R2CSiMe1Bun 70CB1976R1C"SiMe1N2#Li Me1SiHCl R1C"SiMe1N2#"SiMe1H# 39 82JOM"340#34R1C"SiEt1H#Li Me1SiCl1 R1C"SiEt1H#"SiMe1Cl# 54 82JCS"P1#280R1C"SiMe1CH1CH1#Li Me1Si"CH1CH1#Cl R1C"SiMe1CH1CH1#1 59 76JCS"P1#0936R1C"SiMe1CH1CH1#Li Me1SiHCl R1C"SiMe1CH1CH1#"SiMe1H# 56 76JCS"P1#0936R1C"SiMe1CH1CH1#Li Me1SiCl1 R1C"SiMe1CH1CH1#"SiMe1Cl# 55 76JCS"P1#0936R1C"SiMe1CH1CH1#Li TMSCl R2CSiMe1"CH1CH1# 77 76JCS"P1#0936R1C"SiMe1CH1CH1#Li Et1SiCl1 R1C"SiMe1CH1CH1#"SiEt1Cl# 43 76JCS"P1#0936R1C"SiMe1CH1CH1#Li Et1SiHCl R1C"SiMe1CH1CH1#"SiEt1H# 54 76JCS"P1#0936R1C"SiMe1CH1CH1#Li Ph1SiHCl R1C"SiMe1CH1CH1"SiPh1H# 47 76JCS"P1#0936R1C"SiMe1CH1CH1#Li PhMeSiHCl R1C"SiMe1CH1CH1#"SiPhMeH# 58 76JCS"P1#0936R1C"SiMe1CH1SiMe2#Li TMSCl R2CSiMe1CH1TMS 89 80OM440"21# TMSCl "22# 72ZAAC"386#008"24# ClSi"CH1TMS#2 "25# 72ZAAC"386#008*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐa R�TMS[ b Y�p!OMe\ p!Me\ p!Cl or m!CF2[

TMS

TMS

SiMe

PhPhMeSi

SiMePh

TMS

TMS

TMS

TMS

(3) cis and trans

TMS

TMS

Cl

SiPhMeF

TMS

TMS

Li

SiPhMeF

Me2Si

SiMe2

TMS

TMS

TMS

TMS

+ BunLi

x 2

–LiF

(4)

Scheme 1


involving the thermally generated silene "Cl2Si#1C1SiCl1 see 5[02[0[0[0"i#"d#[# Addition of variousorganosilanes to a reactive Si1C bond can also lead to formation of the Si3C function[ Thus\addition of "PhO#1P"O#TMS to the silene "TMS#1C1SiMe1 "4# gives "TMS#2CSiMe1OP"O#"OPh#1ð70CB2494Ł while addition of TMSX gives "TMS#2CSiMe1X "X�Cl\ OMe\ NMe1 or OPh#ð70CB2494Ł and addition of Ph1C1NSiMe2 a}ords "5#\ which when heated at 058>C rearranges togive "TMS#2CSiMe1N1CPh1 "Scheme 1# ð70CB2407\ 76ZN"B#0944\ 76ZN"B#0951Ł[ The silene "4# alsoreacts with SiF3 "but not with SiCl3# to give "TMS#1C"SiF2#"SiMe1F# ð73JOM"162#030Ł[ Addition ofPhCN to two equivs[ of the silene "4# gives "6# which rearranges to give "7# which reacts withmethanol at 059>C to give "8# "Scheme 1# ð70CB2407\ 76ZN"B#0951\ 76ZN"B#0944Ł[

SiMe2

TMS

TMS

N-TMSPh

Ph

Ph N

SiMe2

Me2SiN

PhTMS

TMS

TMSTMS

Me2Si

N

TMS

TMS

Ph

Ph

(TMS)3CSiMe2N

Ph

Ph

Scheme 2

SiMe2

Me2SiN

PhTMS

TMS

(5)

TMS

TMS

(7)

SiMe2OMe

SiMe2OMeTMS

TMS

(6)

169 °C

SiMe2X

TMS

TMS

TMS

(8)

MeOH

160 °C

(9)

TMS-X

X = Cl, OMe, NMe2 or OPh

TMS

Intramolecular elimination of LiBr may also lead to cyclic products "09# from simple Si0Cbond formation "Scheme 2# ð70ZAAC"370#59Ł[ Alternatively\ elimination of LiBr from "00^ n�9#presumably forms silene "01#\ which dimerises to give "02# "Scheme 2# ð70ZAAC"370#59Ł[ The organo!metallic syntheses of carbosilanes are reviewed in ð63TCC32Ł[

Me2Si

SiMe2

SiMe2

BrMe2Si

(CH2—SiMe2)nBr

Me2Si

SiMe2

SiMe2

LiMe2Si

(CH2—SiMe2)nBr

Me2Si

SiMe2

SiMe2

SiMe2

CMe2Si

Me2Si

SiMe2

SiMe2

SiMe2

–LiBr

(11) (10)

Me2Si

SiMe2

SiMe2

n = 1 or 2

Scheme 3

SiMe2Me2Si

SiMe2

Me2Si

Me2Si

BunLi

n = 0

(12)

x 2

(13)

H2

n

The very slow di}usion of oxygen from the air into an Et1O solution of the NMe2 adduct of sileneMe1Si1C"SiMe2#"SiMeBut

1# a}ords "03#[ Although it is unclear how "03# is formed it may again be


via an initial head!to!tail dimerisation of the silene and then further reaction with the oxygenð78ZN"B#685Ł[

Me2Si SiMe2

O

Me2Si

SiMe2

But2MeSi

But2MeSi

(14)

"d# Thermolytic or photolytic methods[ The perchlorotetrasilylmethane "Cl2Si#3C is a high meltingproduct from a {direct synthesis| type of reaction in which CCl3 is passed over an Si:Cu mixture "ina manner reminiscent of the preparation of methylchlorosilanes from MeCl and Si:Cu# at tem!peratures above 299>C[ This again is likely to be a stepwise reaction "as in the in situ couplingsabove# in which C0Cl groups are replaced sequentially by SiCl2 groups ð48CB0907Ł[ Similar reactionsinvolving "Cl2Si#2CCl in SiCl3 or Si1Cl5 over Si:Cu at high temperatures also yield "Cl2Si#3C in up to33) yield[ A surprising coproduct in this type of reaction is "04# which could be formed from thedimerisation of the silene "Cl2Si#1C1SiCl1 ð50EGP11058\ 52CB1783\ 73ZAAC"401#020Ł[ Compound "04#is also formed in 15) yield when "Cl2Si#2CCl is passed over a 09 ] 0 Fe:Cu mixture at 249>Cð53CB0000Ł[ The disilylmethane "Cl2Si#1CCl1 reacts with Si:Cu at 299Ð249>C to give "Cl2Si#3C "04#and the spirocyclic compounds "05^ n�0 to 2# ð76AG"E#0000Ł[ Thermolysis of "06# similarly a}ordsthe spirocyclic compound "07# "Equation 4# ð76AG"E#0000\ 82ZAAC"508#0383Ł[

Cl2Si

SiCl2

SiCl3

SiCl3Cl3Si

Cl3Si

(15)

SiCl2

Cl2Si

SiCl2

Cl2SiCl3Si

Cl3Si SiCl3

SiCl3

(16) n = 1, 2 or 3

n

(17) (18)

SiCl2

SiCl2

Cl2SiCl

Cl

Si

330 °CCl2Si

SiCl2

Cl2Si

SiCl2

Cl2Si

SiCl2

SiCl2

Cl2Si

(5)

The thermolysis of 0\1!disilacyclobutanes "08# with exocyclic double bonds causes rearrangementto a 0\2!disilacyclobutane system "19# or "10# containing an Si3 substituted carbon ð68JA0237\71JOM"125#6\ 77CL0330Ł[ The two types of product "19# and "10# may arise from di}erent mechanisticpathways^ product "19# from a concerted 0\1!silyl shift and product "10# by breakdown of "08# intotwo silenes\ one of which can undergo rapid ligand exchange "which is thought to occur in a numberof other related silenes# to give "11# which then reacts with the silatriene in a head!to!tail fashion togive "10#[ Alternatively\ the two silenes may recombine\ without rearrangement\ in a head!to!tailfashion "Scheme 3# ð68JA0237\ 71JOM"125#6\ 77CL0330Ł[

The gas phase pyrolysis of Me3Si at 699>C a}ords a large number of compounds\ many of whichare carbosilanes containing the 0\2\4\6!tetrasilaadamantane framework[ However\ some that areformed in low yield contain Si2C2 rings having a boat conformation such as "12# and "13# ð62AG"E#543\63ZAAC"393#0Ł[ The pyrolytic preparation of the carbosilanes is not very convenient as it leads to theformation of a large number of products which have to be separated by distillation\ fractionalcrystallisation\ or high!performance liquid chromatography "HPLC# ð73ZAAC"401#82Ł[ The synthesisof carbosilanes by pyrolysis or organometallic synthetic routes has been reviewed ð76AG"E#0000Ł\and discussed in detail ð54MI 502!90Ł[

Photolysis "or thermolysis for R�Me# of the bis"silyldiazomethyl# compounds "14#\ in the absenceof trapping agents\ gives rise to low yields of "15# "a much higher yield is obtained by thermolysis#presumably via dicarbene "16# which undergoes the well!known silylcarbene to silene rearrangementto give "17# which cyclises in a predominantly head!to!tail fashion to give "15# "Scheme 4# ð80JA6689Ł[


(19) (20)

silyl migration•

TMS

TMS

SiR2

R2Si

TMS TMS

•

TMS

TMS

SiR2

R2Si

TMS

TMS

sileneformation

•

TMS

TMS

• + SiR2

TMS

TMS R groupscrambling

SiMe2

RMe2Si

RMe2Si

•

TMS

TMS

SiMe2

R2Si

SiMe2R

SiMe2R

head-to-tailcycloaddition with

(21)

head-to-tailcycloaddition

(20)

(22)

Scheme 4

R = Me, Ph, m-tolyl or p-tolyl

SiR2

•TMS

TMS• SiR2

(23)

MeSiSi

Si SiMe

Si

MeSi

Si

MeSi

MeSiSi

Si SiMe

Si SiSi

Me

Me Me

Me

(24)

RMe2Si SiMe2

Me2Si

SiMe2

SiMe2R

N2 N2

RMe2Si SiMe2

Me2Si

SiMe2

SiMe2R

: :

RMe2Si

Me2Si

RMe2Si

SiMe2

SiMe2

hν

(25) (27)

(26) (28)

Me2Si SiMe2

SiMe2R

SiMe2R

SiMe2

Scheme 5

R = Me or Ph

"e# Transition metal catalysed reactions[ The palladium catalysed reactions between isocyanidesand oligosilanes in the presence of 0\0\2\2!tetramethylbutyl isocyanide gives products "18# fromtetrasilanes ""29# from the hexasilane TMS"SiMe1#3TMS# in which both the C to N triple bond andthree Si0Si bonds have been broken[ The mechanism of this surprising reaction is unclear "thereaction works\ but less well\ in the absence of the butyl isocyanide# but the _rst step is thought toinvolve insertion of the RNC into a terminal Si0Si bond of the oligosilane "Equation "5## ð78"CC#0383\80JA7788Ł[


MeSi

Me2Si

SiMe2

Si

R2R1

R2

MeR1

R3

R3

NC+10 mol% Pd(OAc)2

ButNC

N

Me2Si

SiMe2

R1R2MeSi

R1R2MeSi

R3

R3

(6)

R1 = R2 = R3 = Me, 40%

R1 = R2 = Me, R3 = Pri, 45%

R1 = R2 = Ph, R3 = Me, 31%

R1 = R2 = Ph, R3 = Pri, 62%

(29)

(30)

N

Me2Si

SiMe2

TMS

SiMe2

TMS

Pri

Pri

"f# Rearran`ements of carbosilanes caused by AlBr2[ A range of cyclic compounds containingSi3C functions has been prepared by treatment of a carbosilane containing an Si2C or Si3C centre\to which is attached a carbosilane chain\ with AlBr2[ The reactions proceed at between roomtemperature and 79>C and usually lead to Si0C bond cleavage and formation of Me3Si as a by!product as the ring is formed[ Thus\ "TMS#2C"SiMe1CH1#1TMS "prepared from "TMS#2CSiMe1Cl\see Table 1# initially a}ords cyclic compound "20#\ which reacts further with AlBr2 to give additionalSi3C substituted products "Scheme 5# ð72ZAAC"386#10\ 72ZAAC"386#008\ 72ZAAC"386#023Ł[

Me2Si

SiSiMe2

TMS

TMS

SiMe2

Me2Si

Si

Me2Si

Me TMS

SiMe2

Me2Si

Si

Me2Si

SiMe2

Si

Si

Me2Si

+ Me4SiAlBr3

Me2

(TMS)3C(SiMe2CH2)2TMS

+Br TMS Me TMS

AlBr3

(31)

BrMe

+ CH4 + Me4Si +(TMS)4C + (TMS)3CSiMe2Br +

Scheme 6

Cyclic trisilylmethyllithium reagents may also be used as precursors to complicated carbosilanes^thus "21# reacts with TMSCl to give "22# "see Table 2#\ which reacts with AlBr2 to give "23#\ andlithium reagent "24# can be used to prepare the cyclic compound "25# which contains an Si3Cgroup "see Table 2# "Scheme 6# ð72ZAAC"386#008Ł[ Lithium compounds "51# which are formed by arearrangement "see Section 5[02[0[1[0"i#"a## also react with TMSCl to give tetrasilyl substitutedproducts "26# ð66ZAAC"329#026Ł[


SiMe2

Me2Si

Si

Me2Si

SiMe2

MeSi

Si

Me2Si

Me Li Me Si(CH2TMS)3

Me2

Scheme 7

Me2Si

Si

MeSi

SiSiMe2

Me2Li

Me2Si

Si

MeSi

SiSiMe2

Me2 Me2TMS

(32) (33)

TMS-Cl AlBr3

MeSi SiSi

SiMe

Me2Si

Me2Si

Me

Me

(34)

ClSi(CH2TMS)3

(35) (36)

"ii# Four Ge functions

The abundance of compounds containing the Si3C group discussed in the previous section mightsuggest that at least some similar Ge3C containing compounds should be known[ However\ theredo not seem to have been any compounds containing this grouping prepared[ There would notappear to be any inherent reason why such compounds should not be stable^ ab initio calculationson "H2Ge#3C suggest a greater stability than "H2Si#3Si\ a known stable "albeit highly reactive#compound ð70TCA174Ł[ The reasons for the rarity of tetragermylmethanes are probably the highercosts involved for germanium compounds\ the relative lack of interest in organogermanium chem!istry generally when compared with organosilicon chemistry\ and some of the preparative routesused for the silicon compounds not being readily applicable to corresponding germanium species[It should\ however\ be possible to prepare compounds containing the Ge3C group by\ for example\a route involving sequential metallations of a halomethane followed by reaction with an organo!germanium halide[

"iii# Four B functions

Although the synthesis of such compounds does not seem to have been achieved*calculationson the structures of C"BH1#3 and the spirocycle "27# have been carried out[ Both compounds\ despitethe presence of electropositive substituents and:or small rings\ were found to prefer the usualtetrahedral geometry at carbon rather than a planar geometry ð65JA4308Ł[

Compounds containing the CB3 function can be prepared by an in situ coupling in a mannersimilar to that for CSi3 functions as described above[ Thus the reaction "Equation "6## gives themethanetetraboronic ester in 49Ð59) yield and can be carried out easily on a scale giving 019Ð049g product ð57JA1083\ 58JOM"19#08Ł[ The preparation of ð02CŁC"B"OMe#1#3 starting from ð02CŁCCl3 hasbeen reported to occur in a similar manner ð80AG"E#0377Ł[ Disproportionation of HC"B"OMe#1#2 inthe presence of Et2B also occurs to give low yields of C"B"OMe#1#3 ð64LA0228Ł[ Reactions ofC"B"OMe#1#3 with the a\ v!alkanediols HO"CH1#nOH "n�1 or 2# gives products "28# which havebeen found to be more synthetically useful than the methyl ester ð62JOM"46#120Ł[ The pinacol esterC"BO1C1Me3# is similarly prepared from the methyl ester and pinacol ð63JOM"58#34Ł[

C B

O

O

(39)

( )n

4

n = 2 or 3

Me2Si

SiMe2

SiMe2

TMS

TMS

BH

BHHB

HB

(37) R = H or TMS

B

X

N R

R

TMS

TMS

TMS

(38) (40)

R

R = Me; X = ClR = H; X = F


4ClB(OMe)2 + CCl4 + 8LiTHF

C[B(OMe)2]4 + 8LiCl (7)

Carbon vapour produced from arcing electrodes reacts with B1Cl3 to give C"BCl1#3 as a whitecrystalline solid\ presumably formed by insertion of C atoms into the B0B bond of B1Cl3[ Thereaction of C atoms with B1F3 gives low yields of C"BF1#3 in a similar manner ð58JCS"A#0771Ł[

5[02[0[0[1 Three similar and one different metalloid function

"i# Three Si functions and one Ge function

The reactions of trisilyllithiomethanes with germanium halides proceed in a manner similar tothose described above for silicon halides and the expected products from lithium halide eliminationare formed[ Thus "TMS#1"MeOMe1Si#CLi and Me2GeBr give "TMS#1"MeOMe1Si#CGeMe2 in 78)yield ð76JCS"P1#664Ł[ The disilylgermyllithiomethane "TMS#1"Me2Ge#CLi reacts similarly withMe1SiHCl to a}ord "TMS#1"Me2Ge#CSiMe1H in 35) yield ð76JCS"P1#668Ł[ The reaction of TsiLiwith Me2GeBr\ Me1GeCl1\ Et1GeBr1\ GeCl3\ EtGeCl2\ Et1GeCl1 or Ph1GeCl1 gives TsiGeMe2 "69Ð79)#\ TsiGeMe1Cl "59)#\ TsiGeEt1Br "47)#\ TsiGeCl2\ TsiGeEtCl1\ TsiGeEt1Cl and TsiGePh1Cl\respectively ð69JOM"13#418\ 68JCR"S#01\ 68BAU1111\ 79JOM"191#046Ł[

In a manner reminiscent of the silicon analogues described above\ a germanium halide may alsoadd across the reactive double bond of a silene\ i[e[\ "TMS#1C1SiMe1 reacts with Me2GeCl to give"TMS#1C"GeMe2#"SiMe1Cl# in 74) yield ð76ZN"B#0951Ł[

In an Si2Ge substituted methane the germanium may also be divalent rather than the more usualtetravalent[ For example\ the reaction between TsiLi and Me4C4GeCl gives TsiGeMe4C4 in 51)yield ð80OM2727Ł and in a transmetallation reaction TsiLi reacts with the bulky germyleneC4Me4GeCH"TMS#1 to give TsiGeCH"TMS#1 in 54) yield ð80OM0536Ł[

"ii# Three Si functions and one B function

The reaction of TsiLi with B"OMe#2 does not proceed in the simple manner expected\ but use ofthree equivs[ of B"OMe#2 a}ords\ after an aqueous workup\ a mixture of TsiB"OMe#1\ TsiB"OMe#OH and TsiB"OH#1 ð75JOM"297#150Ł\ while a nonaqueous workup allows TsiB"OMe#1 to beisolated as product in good yield ð78JCS"D#336\ 78CB0946Ł[ Surprisingly\ the reaction between TsiLiand BF2 in Et1O:THF does not a}ord TsiBF1 but rather TsiB"F#O"CH1#3Tsi in 44) yield in whicha ring!opened THF molecule has been incorporated into the product[ The mechanism by which thiscompound is formed is not known in detail^ the product is unusual as reactions between TsiLi andother metal or metalloid halides generally give products derived from the simple elimination of alithium halide ð71JOM"124#154Ł\ and the reaction between TsiLi and Ph1BBr does a}ord TsiBPh1

ð73JOM"161#0Ł[ In contrast to the TsiLi analogue\ the reaction between "PhMe1Si#2CLi and BF2 =Et1Oin THF does give the expected product\ "PhMe1Si#2CBF1\ in 74) yield ð78JCS"D#336Ł[ The lowerreactivity of "PhMe1Si#2CLi compared with TsiLi towards the BF2:THF system and towards othermetalloid halides is probably associated with their di}erence in structure\ the compound containingphenyl being a molecular species and TsiLi ionic "see 5[02[0[1[0"i#"a# for further details of theseorganolithium compounds#[

Addition of BF2 across the reactive double bond of the silene "MeBut1Si#"TMS#C1SiMe1 gives

"MeBut1Si#"TMS#C"BF1#"SiMe1F# in about 69) yield ð72AG"E#0994\ 75CB0356Ł[ Surprisingly\ this

product is also formed in 54) yield from the reaction between "TMS#1CLi"SiBut1F# and BF2\

presumably via rearrangement to "TMS#"FMe1Si#CLi"SiBut1Me# and subsequent formation of the

silene to which the BF2 adds ð75CB0356Ł[ Although the reaction between TsiLi and BF2 is compli!cated\ the reaction between TsiLi and "TMS#1NBF1 a}ords TsiB"F#N"TMS#1 ð74AG"E#213Ł[ Thereaction between PhCH1B"OMe#1 and TsiLi in a 0 ] 0 ratio gives TsiB"OMe#CH1Ph in 35) yieldð89CB636Ł and the reaction between TsiLi and ButBF1 a}ords TsiB"F#But in 67) yield ð78CB0946Ł[TsiLi also reacts with "TMS#RNBF1 "R�Me\ Pri\ TMS\ But

2# to give TsiB"F#NR"TMS# in yields


of 48) "R�Me# and 72) "R�Pri# and with dichloro"1\1\5\5!tetramethylpiperidino#borane togive chloro"1\1\5\5!tetramethylpiperidino#!tris"trimethylsilyl#methylborane "39^ R�Me\ X�Cl# in21) yield ð75CB0006Ł[ Such compounds readily eliminate TMSF to give TsiB2NR species "R�But

or TMS#[ Similarly TsiLi reacts with Pri1N1BF1 to give TsiB"F#NPri

1 in 67) yield ð76CB0958Ł[ Thereaction between TsiLi and "1\5!dimethylpiperidino#di~uoroborane gives the ~uoroborane "39#"R�H\ X�F# as an oil in 60) yield ð78CB484Ł[

"iii# Three Ge functions and one Si or B function[ Also three B functions and one Si or Ge function

No compounds containing these functions seem to have been prepared[ This is not surprising forthe case of the CGe2 compounds when it is taken into account that there are neither CGe3 functionsas described in 5[02[0[0[0["ii# nor CGe2M species[ Again this lack of compounds is not likely to bedue to a problem of inherent instability of such species but rather a lack of interest in their synthesis[The lack of CB2Si or CB2Ge functions is more surprising as both the CB3 function and variousCB2M functions are known "see 5[02[0[1[0"ii# below#[ The synthesis of these mixed metalloidcompounds could probably be easily achieved in a manner similar to those\ for example\ of CB2Snfunctions^ i[e[\ by reaction between a CB2Li function and a silicon or germanium halide such asTMSCl or Ph2GeCl[

5[02[0[0[2 Two similar and two different metalloid functions

"i# Two Si and two Ge functions

When it is considered that there are a large number of compounds containing the CSi3 function\and no compounds containing the CGe3 function known\ it can be expected that there will only bea handful of compounds known which contain the CSi1Ge1 function[ Such compounds have beenprepared using methods that have been widely used for the synthesis of CSi3 functions\ and manymore species could no doubt be prepared in similar ways[ The reaction between the highly reactivedilithiomethane "TMS#1CLi1 and Me2GeCl gives the expected "TMS#1C"GeMe2#1 in 79) yieldð77TL4126Ł[ This compound is also produced as a by!product "in up to 29) yield# from the lowtemperature reaction between "TMS#1CCl1\BunLi and Me2GeBr ""TMS#1C"GeMe2#Cl being thedesired product# ð76JCS"P1#668Ł[ The reaction between Me1GeBr1 and two equivs[ of "TMS#1CBrLiat low temperature gives compounds "30# and "31# in 06 and 3[3) yields respectively[ These productspresumably arise from lithium:halogen exchange after the initial C0Ge bond formation as shownin Scheme 7 ð65JOM"005#146Ł[ Wiberg has shown independently that a variety of lithium compounds"TMS#1C"GeMe1X#Li "X�F\ Br\ OMe\ etc[^ see 5[02[0[1[1"i## eliminate LiX to give germene "32#which does then dimerise ð75CB1855\ 75CB1879Ł[

Br

LiR

R Br

GeMe2BrR

R

Br

LiR

R

Li

GeMe2BrR

R

GeMe2Br

GeMe2BrR

R

R

R

GeMe2

(43)

+ Me2GeBr2

R = TMS

Me2Ge

GeMe2

R

R

+ R2CBr2

Me2GeBr2

(42)(41)

–LiBr

x 2

Scheme 8

R

R

"ii# Two Si\ one Ge and one B function

Compounds containing the CSi1GeB function do not appear to be known[ However\ they arelikely to be readily available from the reaction of one of the several known CSi1GeLi containingcompounds with a boron halide or B"OMe2#[


"iii# Two Si and two B functions

As for the case of the CSi1Ge1 function there are very few compounds known containing theCSi1B1 group[ The reaction of the unsaturated boron compound "33# with RBBr1 species givesproducts "34# "32) yield# and "35# "42) yield# that are the result of a formal addition across theC1B bond "Scheme 8# ð78CB484Ł[

Scheme 9

(46)(44)

(45)

+ BBr3

MeBBr2

B NPri2

TMS

TMS

B

NPri2

BrBr2B

TMS

TMS B

NPri2

BrMeBrB

BrMe2Si

TMS

B

NPri2

BrMeBrB

TMS

TMS

The reactions of the dilithium reagent "36# give a variety of cyclic compounds containing theCSi1B1 function "see also Equation "05## which appear to arise via an intramolecular cyclisation anda double substitution at the triply bonded carbon "Scheme 09# ð78AG"E#670\ 78AG"E#673Ł[

Scheme 10

(47)

F2BArB

Ar

B Ar

TMS

TMS

LiLi Ar

B

BAr

BArTMS

TMS

Ar = mesityl, 92%Ar = 2, 3, 5, 6-Me4C6H, 81%

ArB

BAr

TMS

TMS

Ar = 2, 4, 6-Me3C6H2, 89%Ar = 2, 3, 5, 6-Me4C6H, 100%

2 MeI

The unsaturated borane "72# "see 5[02[0[1[1"ii## reacts with Ar1BBF1 to give the cyclic species "37#which rearranges slowly to give "38# "Equation "7##[ This has been structurally characterised byx!ray crystallography ð80AG"E#483Ł[

Ar = 2, 4, 6-Me3C6H2Ar1 = 2, 3, 5, 6-Me4C6H or 2, 4, 6-Me3C6H2

(48)

BBAr1

Ar1

B

TMS

TMSAr2B

B

TMS

TMSAr2B

Ar1B BAr1

(8)

(49)

Treatment of the dianion "49# with Ph2PAuCl or CH1Br1 gives compounds "40#\ "41# and "42# in11\ 29\ and 42) yields respectively\ all of which seem to have been formed via a silyl migration anda geminal substitution "Scheme 00# ð75AG"E#0001\ 78CB0770Ł[

"iv# Two Ge and two B functions[ Also two Ge\ one Si and one B function[ Also two B\ one Si and oneGe function

As might be expected from the paucity of CSi1Ge1 and CSi1B1 containing species\ there appear tobe have been no compounds prepared containing the CGe1B1\ CGe1SiB\ or CB1SiGe functions[Again there is not likely to be any good reason why such compounds should not be made[ Reactionsbetween appropriately substituted lithiomethanes and halometalloids should readily a}ord therequired functions[


NPri2

B

BNPri

2

(50)

+ Ph3PAuCl0 °C

NPri2

B

BNPri

2

AuPPh3

AuPPh3TMS

TMS

(51)

NPri2

B

BNPri

2

TMS

TMS

(53)

CH2Br2

NPri2

B

BNPri

2

TMS

TMS

(52)

AuPPh3

Ph3PAuCl–50 °C

Scheme 11

2–

TMS TMS

5[02[0[1 Methanes Bearing Three Metalloid Functions and a Metal Function

5[02[0[1[0 Three similar metalloid functions

"i# Three Si functions

"a# Three Si and one `roup 0 metal function[ The "TMS#2C "Tsi# group has been attached to awide variety of metals and metalloids usually using the lithium reagent TsiLi[ The bulk of the Tsigroup means that molecules containing it often have novel structures or contain elements in unusualoxidation states[ The size of the Tsi group has been discussed in terms of a {cone angle| "a termmore commonly used in phosphine chemistry# and when attached to Si\ Ge\ or Sn it has a coneangle of 197>\ 085>\ and 089> respectively ð80MI 502!90Ł[

The metallation of TsiH by MeLi in THF:Et1O occurs readily to give a dark\ redÐbrown solutionof TsiLi in about 5 h at the re~ux temperature or 19 h at room temperature ð69JOM"13#418\ 66CB741Ł[Improvements to this preparation have been reported[ These involve removal of the Et1O from thereaction solution by distillation\ thus allowing a higher re~ux temperature and complete metallationin 1 h^ removal of any residual MeLi from the reaction mixture by addition of TMSOMe orTMSOEt which reacts with MeLi but not TsiLi^ determination of the extent of reaction by treatmentof an aliquot of the reaction solution with TMSCl and determining the "TMS#3CÐ"TMS#2CH ratioby 0H NMR spectroscopy ð73JOM"158#106Ł[ The TsiLi produced in this way is remarkably stable foran alkyllithium reagent\ a 9[04 M solution in THF having a half!life in re~uxing THF of 69 hð69JOM"13#418Ł[ The ease of preparation\ relative stability "and hence relative ease of handling# andthe steric requirements of the bulky Tsi group have made TsiLi a useful and widely applicablereagent in the preparation of unusual organometallic compounds many of which are describedelsewhere in this chapter[

Metallation of TsiH does not occur with BunLi:Et1O:THF\ BunLi:C4H01:TMEDA\ ButLi:C4H01\or ButLi:THF[ As these are more powerful metallating agents than MeLi\ steric e}ects would seemto play an important role in these reactions ð62JOM"44#198Ł[ The addition of the base hexa!methylphosphoric triamide "HMPT# to reaction solutions does\ however\ promote metallation andTsiLi is formed in good yield from TsiH using ButLi:THF:HMPT as the metallating agent at−67>C ð74CB1382Ł[ "See below for the reaction between TsiH and ButLi:C4H01:TMEDA at roomtemperature[# When prepared in THF from TsiH and MeLi\ the TsiLi may be isolated as a crystallinesolid in 54) yield[ Characterisation by x!ray crystallography shows that\ in the solid state\ thelithium compound is not simply TsiLi\ but that it actually has an unusual ate composition "Tsi1Li#"Li"THF#3# ð72CC716Ł[ In THF or toluene solution the unusual ionic form is also predominant\but at low temperatures and low concentration a second form thought to be TsiLi"THF#n "n�0 or1# can be detected by NMR spectroscopy[ A di}erent form\ thought to be an aggregate of somekind\ is also observed in toluene[ At higher temperatures the two forms interconvert rapidly on theNMR timescale and the 0H NMR signal for the TMS groups is commonly seen as a broad singletat 89 MHz or two singlets at 299 MHz at room temperature ð82JCS"D#2148Ł[


Preparation of TsiLi may also be achieved by reaction of TsiBr with BunLi "at −64>C#\ PhLi orwith lithium metal ð66JOM"031#28\ 81OM1827Ł[ These methods give good yields which may be deter!mined by derivatisation with TMSCl\ but the method involving the metallation of TsiH by MeLi isto be preferred in most cases as TsiH is much more readily available than TsiBr[ TsiLi may also beprepared by treatment of TsiSPh with Linaphth:THF at −67>C^ however\ this is again not a veryconvenient route as the phenylthio starting material is much more di.cult to prepare than TsiH[However\ this route may be of use on occasions when a complete absence of halogen in the systemis required as the methods involving transmetallation using\ for example\ MeLi or BuLi usuallyhave some residual halogen present from the lithium reagents preparation ð73JOC057Ł[

TsiLi as a TMEDA adduct "Tsi1Li#"LiTMEDA1# is formed in 53) yield by metallation of TsiHin hexane in the presence of TMEDA over 79 h at room temperature ð76CB0958Ł[ The reactionbetween TsiH and MeLi "evidently containing some LiCl from the MeLi preparation# in thepresence of Me1N"CH1#1NMe"CH1#1NMe1 "PMDETA# again gives a TsiLi!like species[ Againcrystallography shows that an ate species is present in the solid state\ this time containing a novel\linear\ chlorine centred cation as shown in "43# ð75CC858Ł[ The reaction between TsiHgBun andBunLi at 54Ð69>C in the absence of solvent gives the highly reactive\ solvent!free TsiLi which hasbeen characterised by x!ray crystallography and found to be a bridged dimer "TsiLi#1 in the solidstate[ Although this synthesis of TsiLi requires several more steps than the others described\ theabsence of solvent\ particularly THF*which can cause side reactions when the lithium reagent isused*may mean that this is the method of choice if a coordinated solvent is likely to be troublesomeð80AG"E#213Ł[

(54)

Li

TMS

TMS TMS

TMS

TMS TMS

–+

Li Cl Li NMe

Me2N

Me2N

NMe2

MeN

NMe2

The metallation of "PhMe1Si#2CH with MeLi proceeds in a similar manner to TsiH to give"PhMe1Si#2CLi which can be isolated as a solid in 56) yield[ This reagent is generally less reactivethan TsiLi "it does not react with TMSCl or Me1SiCl1# and has been found to have a monomericstructure "44# in the solid state ð72CC0289\ 74JCS"P1#618Ł[

(55)

Me2Si

Li

PhMe2Si

PhMe2Si

THF

The metallation of several other Si2CH functional trisilylmethanes by MeLi or BunLi has alsobeen reported to occur easily and to give preparatively useful reagents[ For example\ compounds"21# and "24# are formed from the corresponding C0H compounds by treatment with MeLi:THFand with BunLi:TMEDA respectively ð72ZAAC"386#008Ł[ The lithium reagent "TMS#1"PhMe1Si#CLiis formed from the metallation of "TMS#1"PhMe1Si#CH with MeLi in re~uxing THF ð76CC0350Ł\and trisilylmethane "45# is also metallated by MeLi to give "46# "Equation "8## ð72ZAAC"386#10Ł[ Thetrisilylmethane derivative "47# may also be metallated by MeLi in THF:Et1O "Equation 09# to givelithium reagent "48# but little chemistry has been carried out with the reagent ð77JOM"230#098Ł[

(56)

Me2Si

SiMe2

SiMe2

SiMe2Ph

(57)

Me2Si

SiMe2

SiMe2MeLi

SiMe2PhLi

(9)


Me2Si

MeSi

MeSi

MeSi

SiMe2

Me2Si

Me2Si

MeSi

MeSi

MeSi

SiMe2

MeLi

(58) (59)Li

(10)Me2Si

The stabilising e}ect of three a!silyl groups can be seen in the reactions of species "59# withBunLi:TMEDA[ The initial reaction products are the HSi1C carbanions "50# but these rearrange togive the more stable Si2C carbanions "51# "Equation "00## ð66ZAAC"329#026Ł[

(60) R = H or TMS

BunLi/TMEDAMe2Si

SiMe2

SiMe2

TMSR

(61)

Me2Si

SiMe2

SiMe2

TMSR

Li

(62)

Me2Si

SiMe2

SiMe2

RLi

TMS(11)

More reactive metallating agents such as ButLi:TMEDA and BunLi:ButOK react readily with"TMS#1CHSiMe1CH1TMS to give "TMS#1CLiSiMe1CH1TMS in ×89) yield ð80OM440Ł[ This is\perhaps\ surprising as although the carbanion is stabilised by three a!silyl groups "rather than twoif the CH1 group had been metallated# reaction of the closely related "TMS#2CH with ButLi:C4H01:TMEDA gives "TMS#1CHSiMe1CH1Li in which metallation of a methyl group ratherthan the central methine CH has occured ð62JOM"44#198Ł[ The highly sterically hindered ~uorosilaneBut

1FSiCH"TMS#1 reacts with MeLi in THF at room temperature over a period of a week togive the alkyllithium reagent But

1FSiCLi"TMS#1 which rearranges over a period of weeks to giveMe1FSiCLi"TMS#"SiBut

1Me# which has been characterised by x!ray crystallography ð76OM24Ł[ Themetallation of the central carbon by MeLi rather than substitution of F for Me on the silicon issurprising and is presumably due to the severe steric hindrance at the silicon bearing the ~uorinetogether with the fact that the carbanion formed is stabilised by three a!silyl groups ð72AG"E#0994\73JOM"160#270\ 75CB0344Ł[

The formation of Si2LiC functions may also be achieved from Si2XC substituted methanes"X�halogen# using either other lithium reagents or lithium metal[ A range of substituted arylsilanes "TMS#1"YC5H3Me1Si#CCl "Y�H\ p!OMe\ p!Me\ p!Cl\ m!CF2# reacts with BunLi at −009>Cto give the corresponding lithium reagents "TMS#1"YC5H3Me1Si#CLi which react readily withchlorosilanes to give Si3C containing compounds ð83JOM"355#24Ł[ A range of "TMS#1"XMe1Si#CLispecies may be prepared according to the general Equation "01#[ Such compounds are usefulprecursors to "TMS#1C1SiMe1 via LiX elimination "which takes place readily except whenX�MeO\ PhO\ Bun or Ph which are stable# and the lithium reagents are not\ therefore\ usuallyisolated as pure compounds ð66AG"E#217\ 70CB1976\ 70CB2494\ 70CB2407\ 75JOM"204#8Ł[ The reactionbetween "TMS#1"MeOMe1Si#CCl and BunLi in THF:hexane at −79>C gives "TMS#1"MeOMe1Si#CLi which reacts with silyl halides to give CSi3 functions ð76JCS"P1#780Ł[ The reagentcan similarly be prepared at −009>C in THF:Et1O:pentane ð81JOM"326#30Ł[ The phenyl containingcompound "TMS#1"PhMe1Si#CLi can be prepared from the corresponding chloride using BunLi at−009>C ð81JOM"326#30Ł[ The vinylsilane "TMS#1"CH11CHMe1Si#CCl and BunLi at −099>C inTHF:Et1O:pentane gives the organolithium compound "TMS#1"CH11CHMe1Si#CLi which reactswith various organosilicon halides to give tetrasilylmethanes ð76JCS"P1#270\ 76JCS"P1#0936Ł[ The silylhydride "TMS#1"HMe1Si#CCl reacts with BunLi at −009>C in THF:Et1O:pentane to give "TMS#1"HMe1Si#CLi ð81JOM"326#30Ł[

Br

SiMe2XTMS

TMS Li

SiMe2XTMS

TMS(12)

< –78 °C+ BunLi + BuBr

X = F, Cl, Br, I, OMe, OPh, Ph, Bun, Ph2, PO2, etc.

The reaction of "TMS#1CBr"SiPh1X# "X�F or Br# with PhLi gives the corresponding lithiumreagents "TMS#1CLi"SiPh1X# "again substitution of Ph for X does not occur#[ The Si0H compounds


"TMS#1CM"SiPh1H# "M�Li or Na# are also formed in good yield from the reaction between"TMS#1CBr1\ Ph1SiHCl and M in THF at −67>C[ Treatment of "TMS#1CBr"SiPh1Br# with twoequivs[ of RLi or treatment of "TMS#1CLi"SiPh1Br# with a second equiv[ of RLi a}ords furthertrisilyllithium reagents "TMS#1CLi"SiPh1R# "R�Me\ Bun\ Ph or OPh# ð78CB398Ł[ The metallation ofa trisilylmethylhalide may also be accomplished by reaction with lithium metal[ Thus\ "PhMe1Si#2CClreacts with two equivs[ of lithium to give "PhMe1Si#2CLi and LiCl ð66ZAAC"329#010Ł[ Lithium reagent"ClMe1Si#1CLi"SiMe1CCl1H# is probably formed as an intermediate "which rapidly eliminates LiCl#on treatment of "ClMe1Si#1CCl"SiMe1CCl1H# with BunLi ð66ZAAC"329#010Ł[

The methoxysilane "MeOMe1Si#2CCl reacts with BunLi at −67>C to give the lithium compound"MeOMe1Si#2CLi which\ in the solid state\ is actually a dimer\ ð"LiC"SiMe1OMe#2#1Ł having theunusual structure "52# where the lithium atoms are solvated intramolecularly by the methoxy groupsrather than by solvent molecules ð75CC0932Ł[

Li

Si O

Li

SiO

O Si

Si O

Si

O

O

Si

(63)

Coordination around the central carbonin [{LiC(SiMe2OMe)3}2].Methyl groups have been omitted for clarity.

The reaction between TsiH and methylsodium in Et1O in the presence of TMEDA gives adialkylsodiate "Na"TMEDA#"Et1O#"NaTsi1# containing a linear "Tsi0Na0Tsi#− anion in a mannersimilar to the metallation of TsiH by MeLi described above ð83AG"E#0157Ł[ A sodium reagentformulated as TsiNa\ which can be derivatised with MeI to give TsiMe\ appears to be formedin low yield in the reaction between "TMS#3C and NaOMe:hexamethylphosphoramide"HMPA#ð62TL3082Ł[ The alkylpotassium compounds TsiK and "PhMe1Si#2CK may both be made in twoways^ either by treating the analogous lithium reagents with ButOK\ or by treating the parenthydrocarbons with MeK\ the latter being preferred ð83OM642Ł[

"b# Three Si and one `roup 1 metal function[ The highly reactive source of magnesium "Mg"an!thracene#"THF## reacts with TsiCl in THF at 9>C to give the Grignard reagent TsiMgCl in 89)yield ð77JOC2023Ł[ The analogous bromide can also be prepared in 64) yield "determined by doubletitration# from the reaction between TsiBr and Mg in Et1O ð81OM1827Ł[ The reaction betweenmagnesium etherate and TsiLi in a 0 ] 0 ratio gives complex "53# "characterised by x!ray crys!tallography# ð77JCS"D#270Ł[ When "53# is heated it decomposes to give the lithium!free derivativeTsi1Mg which x!ray crystallography reveals has the linear structure "54# ð77JCS"D#270\ 78CC162Ł[Although this compound would appear to have potential as a mild alternative to TsiLi for theintroduction of the Tsi group into compounds it is rather unreactive[ For example\ it does not reactreadily with CO1\ MeI\ Me2COCl or TMSCl[ This is presumably because of the steric protection ofthe C0Mg bonds by the bulky alkyl groups ð78CC162\ 83JOM"379#088Ł[ The reaction between TsiBrand Mg in THF gives complex "55#[ Reactions of this type are complicated by the presence of MgBr1which arises from the reaction of Mg with BrCH1CH1Br used to activate the Mg ð83JOM"358#018Ł[

(64)

BrMg

Br

Li(THF)2

(THF)2

TMS

TMSTMS

(65)

Mg

TMS

TMSTMS

TMS

TMS TMSMg Br

TMS

TMS

TMS Mg(THF)3

Br

Br

(66)

"c# Three Si and one `roup 01 metal function[ The reaction of about 0[4 equivs[ of TsiLi with ZnCl1\CdCl1\ or HgCl1 a}ords the Tsi1M species in 31\ 11 and 24) yields respectively ð79JOM"089#090Ł[ Abetter yield is obtained in the reaction between two equivs[ of TsiLi "evidently containing someresidual MeLi from the metallation of TsiH# and anhydrous ZnCl1 which a}ords a mixture ofTsi1Zn "50)# and TsiZnMe "01)# as crystalline solids ð80JOM"310#064Ł[ These compounds areremarkably thermally and chemically stable because of the high degree of steric hindrance providedby the two bulky Tsi groups to the reactive M0C bonds ð79JOM"089#090Ł[ The reaction of TsiLiwith ZnX1 in a 0 ] 0 stoichiometry a}ords ð"TMS#2C#nXn¦0ŁLi[1THF =Et1O species "X�Cl\ n�1^X�Br\ n�0#^ the chloride reacts with a variety of lithium reagents to give TsiZnR compounds"R�Me\ Bun\ "TMS#1CH\ Tsi\ "TMS#1N\ etc[# ð83JOM"358#024Ł[


The reaction between "PhMe1Si#2CLi and anhydrous ZnCl1 in THF gives a product formulatedas Li"THF#1""PhMe1Si#2CZnCl1#\ probably having structure "56#[ When heated\ "56# a}ords asublimate "PhMe1Si#2CZnCl which is dimeric in the solid state "as are the analogous Cd and Hgcomplexes formed in a similar way# and which can be hydrolysed to give the corresponding hydroxide"PhMe1Si#2CZnOH ð75CC897\ 82JOM"351#34Ł[ In the solid state this unusual alkylzinc hydroxide hasthe OH bridged dimeric structure "57# ð75CC897Ł[ Reaction of the lithium reagent "TMS#1"HMe1Si#CLi with MBr1 a}ords ""TMS#1"HMe1Si#C#1M "M�Zn\ Cd or Hg# species in 07 and 19)yields for the M�Cd and Hg compounds respectively[ The Zn compound reacts with variouselectrophiles such as Br1 and CF2CO1H to give compounds that are the products from reactionswith the Si0H groups rather than the C0Zn bonds ð76JOM"219#026\ 89CC0360Ł[ The reaction ofZnBr1 with two equivs[ of the lithium reagents "TMS#1"XMe1Si#CLi a}ord ""TMS#1"XMe1Si#C#1Znin yields of 67 and 49) for X�H and X�OMe respectively ð81JOM"326#30Ł[ Similarly the reactionsof CdCl1 with "TMS#1"XMe1Si#CLi reagents a}ord ""TMS#1"XMe1Si#C#1Cd in yields of 39\ 55\and 29) respectively for X�H\ OMe and Ph ð81JOM"326#30Ł[ The reaction of two equivs[ of"TMS#1"MeOMe1Si#CLi with HgBr1 at −009>C gives ""TMS#1"MeOMe1Si#C#1Hg in 29) yieldð80JOM"394#038Ł[

(67)

Cl

ZnCl

Li(THF)2

PhMe2Si

PhMe2Si

PhMe2Si

HO

ZnOH

Zn

PhMe2Si

PhMe2Si

PhMe2Si

SiMe2Ph

SiMe2Ph

SiMe2Ph

(68)

The reaction of one equiv[ of TsiLi and one of CdBr1 in Et1O:THF a}ords\ after crystallisingfrom cyclohexane\ a 10) yield of the trimeric bridged complex "Li"THF#3#""CdTsi#2"m!Br#2"m2!Br##\the anion of which has the structure "58#\ which is based on a cube with one corner missing[ Asecond product "69# may be obtained from the reaction in 02) yield by extraction of the reactionresidue with heptane[ The mechanism by which "69# is formed is not known in detail but it is likelyto involve some accidental hydrolysis and formation of LiOTMS ð77JCS"D#270Ł[ The reaction ofslightly less than one equiv[ of TsiLi and CdCl1 gives some Tsi1Cd and a 49) yield of TsiCdCl1Li"THF#[ On sublimation\ the complex breaks down to give TsiCdCl ð77JCS"D#270Ł[ X!ray crys!tallography shows that the lithium salt and the alkylcadmium chloride have\ in fact\ the dimeric andtetrameric structures "60# and "61# ð77CC0278Ł[ A similar complex\ Li"THF#1CdBr1"C"SiMe1Ph#2#\ isformed in the reaction between "PhMe1Si#2CLi and CdBr1^ this also breaks down on heating to give"PhMe1Si#2CdBr ð77JCS"D#270Ł[ This complex\ which readily forms a hydrate when crystallised fromwet THF\ has also been shown to have a dimeric structure "62# ð77CC0278Ł[

(69)

Br

Cd Br

Cd

Br Cd

Br

R

R

R

R = (TMS)3C

Cd BrBr LiTHF

O

(TMS)3C

LiBr Li

(70)

THF

THF TMS

(71)

Cl

CdCl

Cd

ClLi

ClC(TMS)3(TMS)3C

(THF)2

CdCd Cl

CdClCl

R

R

RR = C(TMS)3Cd

Cl

R

(72)

Br

Cd

Br

Cd C(SiMe2Ph)3(PhMe2Si)3C

(73)

The reaction between one equiv[ of TsiLi and HgCl1 in re~uxing THF:Et1O a}ords Tsi1Hg in a09) yield "19) yield is obtained if HgBr1 is used instead of the chloride# as a colourless solid\ whilereaction of TsiLi with HgBrMe gives TsiHgMe in 31) yield ð66JCR"S#005Ł[ The reaction betweenone equiv[ of TsiLi and HgBr1 at 9>C a}ords TsiHgBr in a yield of 62) ð80AG"E#213Ł[ This bulkyalkylmercury bromide reacts with Grignard reagents to give TsiHgR species "R�Me\ Pri\ But or Ph#and the chloride "PhMe1Si#2CHgCl with lithium reagents or PhCH1MgCl to give "PhMe1Si#2CHgRcompounds "R�Me\ Bu\ Ph\ Tsi or PhCH1# ð84UP 502!90Ł[ The bromide TsiHgBr is also formedin the reaction between "Fe"CO#3"HgTsi#1# "obtained from the reaction between TsiHgCl and


"Fe"CO#3#1−# and either HgBr1 or "Fe"CO#3"HgBr#1# ð68JCS"D#656Ł[ The reaction of HgBr1 with oneequiv[ of the lithium reagent TMS1"H1C1CHMe1Si#CLi a}ords TMS1"H1C1CHMe1Si#CHgBr in14) yield ð76JOM"219#026Ł[ The reaction of HgCl1 and slightly less than two equivs[ of TsiLi inre~uxing Et1O has also been reported to give a 69) yield of Tsi1Hg and between HgCl1 and slightlyless than two equivs[ of TsiMgBr a 71) yield of the same dialkylmercury species[ This is one of thefew examples known of the use of a reagent other than TsiLi for the introduction of the Tsi groupð81OM1827Ł[

"d# Three Si and one `roup 02 metal function[ A low yield of TsiAlCl1 is obtained from thereaction between TsiLi and AlCl2 in THF:Et1O[ The low yield is probably due to the THF reactingand forming compounds of the type TsiAl"Cl#O"CH1#3Tsi as seen in the case of the reaction withBF2 "See 5[02[0[0[1"ii## ð72JOM"138#12Ł[ "See below for the formation of a further TsiAl derivativeformed by reduction of a TsiTl species[#

The reaction of Ga1Br3 = 1 dioxane with TsiLi coordinated to ether solvents "THF or Et1O# leadsonly to the isolation of TsiH but if solvent!free TsiLi is used "see 5[02[0[1[0"i#"a## then the unusualtetragallium tetrahedrane "63^ M�Ga# is formed as an air!stable solid in 45) yield[ The indiumanalogue of "63^ M�In# is similarly formed from TsiLi and In1Br3 = 1 TMEDA ð81AG"E#0253Ł[ Thebulky lithium reagents "PhMe1Si#2CLi and TsiLi react with GaCl2 to give products of formulaLi"THF#1GaCl2R "R�"PhMe1Si#2C or Tsi# in 81 and 43) yields respectively[ For the case whenR�"PhMe1Si#2C x!ray crystallography has shown that the structure of the alkylgallium complexhas the chlorine bridged structure "64# ð76JCS"D#636Ł[ The reaction between an excess of TsiLi"evidently containing some residual MeLi# and GaCl2 gives a solid thought to be TsiGa"OH#Mewhich is presumably formed by hydrolysis of TsiGaClMe in the work up ð72JOM"138#12Ł[

MM

M

M

C(TMS)3

C(TMS)3(TMS)3C

C(TMS)3

(74)

M = Ga or In

(75)

Cl

GaCl

Li(THF)2

Cl

(PhMe2Si)3C

The reaction between InCl2 and TsiLi gives a complicated alkylindium halide "65# containingcoordinated LiCl[ The indium complex has been reduced using LiAlH3 to give a complex metalhydride "66# which when hydrolysed gives a cage compound "O"TsiIn#3"OH#5# having the structure"67# ð75CC897\ 76JCS"D#636Ł[

Cl

Cl

In(TMS)3C ClLi(THF)3

(76)

H

InH

In

HLi

H

C(TMS)3(TMS)3C

H

(THF)2

(77) (78)

HO

In

OH

InOH

In

OH

R

R OH

O

In

OH

R

R

The reaction between TlCl2 and TsiLi gives a compound formulated as Li"THF#TlCl2C"TMS#2in 34) yield but it is not clear whether this compound has a structure containing two bridging Clsas in the gallium complex "64# above\ only one bridging Cl as in the indium compound "65#\ orsome other structure[ It is likely\ however\ that at least two Cls bridge to the Li in order to satisfythe coordination sphere of the Li present[ Reduction of the thallium compound with LiAlH3 leadsto transfer of the Tsi group and the formation of Li"THF#2AlH2Tsi ð76JCS"D#636Ł[

"e# Three Si and one `roup 03 metal function[ The reactions between TsiLi and Me2SnCl\Ph2SnCl\ "PhCH1#1SnCl1\ SnCl3\ EtSnCl2\ Me1SnCl1\ Ph1SnCl1\ or SnBr3 a}ord TsiSnMe2 "79)#\TsiSnPh2 "23)#\ TsiSn"CH1Ph#1Cl "30)#\ TsiSnCl2\ TsiSnEtCl1\ TsiSnMe1Cl\ TsiSnPh1Cl andTsiSnBr2 "containing some impurities# respectively ð68BAU1111\ 89JCS"D#1532Ł[ Treatment of"Me2Sn#3C with one equiv[ of MeLi followed by one equiv[ of TMSCl gives a low yield of TsiSnMe2

together with a variety of other tetrametallomethanes ð74JOM"180#068Ł[ The reactive silene"TMS#1C1SiMe1 undergoes addition with Me2SnCl to give "TMS#1C"SiMe1Cl#"SnMe2#


ð76ZN"B#0951Ł[ The reaction of "PhMe1Si#2CLi with Me1SnCl1 in THF:Et1O gives "PhMe1Si#2CSnMe1Cl in 79) yield ð76JOM"214#006\ 77JOM"244#22Ł[ This is in contrast to the lack of reactionbetween "PhMe1Si#2CLi and Me1SiCl1\ the longer C0Sn bond length presumably lowering thedegree of steric hindrance at the central carbon[ The reaction of TsiLi with Me1SnCl1 and Ph1SnCl1gives TsiSnMe1Cl and TsiSnPh1Cl in 64 and 39) yields respectively ð77JOM"244#22Ł[ The reactionof the related lithium reagent "TMS#1"Me2Sn#CLi with Me1SiCl1\ TMSCl or Me1SiHCl gives"TMS#1"Me2Sn#CSiMe1X species "X�Cl\ Me\ or H# in 64\ 73\ and 59) yields respectivelyð77JOM"244#22Ł[

The reactions of TsiLi with lead halides proceed in a manner similar to those for the tincompounds[ Thus reactions with Me2PbCl\ Et2PbCl and Ph2PbCl a}ord TsiPbMe2 "68)#\ TsiPbEt2"48)# and TsiPbPh2 "49)# respectively ð71ICA"47#038Ł[ The reaction between two equivs[ of TsiLiand Ph1PbCl1 does not lead to formation of Tsi1PbPh1 "presumably because of the severe stericrepulsion between two Tsi groups at a tetrahedral centre# but rather to the unexpected dileadcompound TsiPbPh1PbPh2 in 18) yield ð82JCS"D#1780Ł[

"f# Three Si and one transition metal function[ The reaction between 0 equiv[ of TsiLi and MnCl1gives a product "Li"THF#3#"Tsi2Mn2Cl3THF# "68# in 59) yield which may be regarded as an{alkylmanganese chloride|[ Reaction of TsiLi with CoCl1 is thought to give a similar cobalt con!taining species ð74CC423\ 77JCS"D#270Ł[ The monomeric two!coordinate manganese complex Tsi1Mnis formed in ca[ 54) yield as a pale yellow solid from the reaction between 1 equiv[ TsiLi andMnCl1 in THF ð74CC0279Ł[ The preparation of Tsi1Ni has been reported but few details of thecompound are available ð60SAP6993811Ł[

(79)

Cl Mn

Cl

MnCl

Mn Cl

C(TMS)3

C(TMS)3

(TMS)3C

THF

–

[Li(THF)4]+

The Gilman reagent "Li"THF#3#"CuTsi1# may be isolated as a solid in 15) yield from the reactionbetween TsiLi and CuI[ As in the case of other Tsi1M species there is a linear Tsi0M0Tsiarrangement in the solid state ð73JOM"152#C12Ł[ The reaction between TsiLi and AgI in THF givesthe ate complex "Li"THF#3#"Tsi1Ag# as a colourless solid in 69) yield which has been structurallycharacterised ð73CC769Ł[ The reaction of TsiLi with LAuCl"L�Et2P\ Ph2P or Ph2As# gives TsiAuLcomplexes as stable white crystalline solids ð67JCR"S#069Ł[

"ii# Three Ge functions

As has been seen in sections above there is a general lack of compounds containing severalgermanium atoms attached to the same carbon and there do not appear to be any compoundscontaining the Ge2MC grouping known[ Such compounds should be readily available via the routesused to prepare the many analogous Si2MC containing functions as described above[

"iii# Three B functions

The CB3 substituted compound C"B"OMe#1#3 reacts with bases MeLi\ LiOMe or BunLi to give acompound that may be formulated as C"B"OMe#1#2Li which reacts with Ph2SnCl or Ph2SnBr to giveC"B"OMe#1#2SnPh2 in 41 and 54) yield respectively ð58JA5430\ 62JOM"46#114\ 63JOM"58#42Ł[ The lith!ium compound also reacts with Me2SnCl to give C"B"OMe#1#2SnMe2\ but rapid disproportionationin the case of similar lead species means that C"B"OMe#1#2PbPh2 cannot be isolated from the reactionbetween the lithium reagent and Ph2PbCl ð58JA5430\ 62JOM"46#114Ł[ The pinacol ester C"BO1C1Me3#3also reacts with MeLi to give C"B1C1Me3#2Li in a similar manner ð63JOM"58#42Ł[ These lithiumreagents would no doubt react with a wide range of other metal and metalloid halides allowing alarge number of currently unknown CB2M functions to be prepared[


5[02[0[1[1 Other mixed metalloid functions

"i# Two Si\ one Ge and one metal function

Compounds of the general type "TMS#1C"XMe1Ge#CBr "X�F\ Br\ OMe\ OPh\ SPh\ "PhO#1PO1\etc[# react with BunLi or PhLi at low temperature "−67 to −019>C# to give lithium compounds"TMS#1"XMe1Ge#CLi\ many of which are thermally unstable\ eliminating LiX to give the germene"TMS#1C1GeMe1 in a manner analogous to that of the trisilyl substituted compounds "see5[02[0[1[0"i## ð75CB1855\ 75CB1879Ł[ The metallation of "TMS#1"Me2Ge#CCl can similarly be achievedby BunLi at −009>C to give "TMS#1"Me2Ge#CLi which is relatively thermally stable ð76JCS"P1#668Ł[This lithium compound would almost certainly react with many metal and metalloid halides to givea wide range of CSi1GeM species if required[

The reaction of "TMS#1"FMe1Ge#CBr with But2SiNa gives a quantitative yield of the cyclic species

"30# "see 5[02[0[0[2"i##[ This presumably arises by dimerisation of the germene "TMS#1C1GeMe1

formed by the elimination of NaF from the highly reactive "TMS#1"FMe1Ge#CNa intermediateð75CB1855\ 75CB1879Ł[

"ii# Two Si\ one B and one metal function

The reduction of "79# with four equivs[ of lithium "Scheme 01# a}ords the unsaturated boroncompound "70# which may also be written as its tautomer "71#[ Mono protonation a}ords acompound analogous to "70# containing the "TMS#1CH group which suggests that one of the lithiumatoms was associated with the Si1B substituted carbon ð77AG"E#850Ł[ The structure of the 1\2\4\5!Me3C5H analogue of "70# and "71# in the solid state shows that the structure is actually betterrepresented by "72# ð89AG"E#0921Ł[

B

B

Mes

Cl

Mes

Cl

TMS

TMSMes B B

Mes

C BMes B

Mes

TMS

TMS+ 4Li 2LiCl +

Li Li

(80) (81)

TMS

Li

TMS

(82)

Scheme 12

B C B

Li

Li

Ar

Et2O

Et2O

Ar

TMS

TMS

(83)Ar = 2, 3, 5, 6-Me4C6H

The addition of lithium to "TMS#1C1BAr "Ar�mesityl or 1\2\4\5!tetramethylphenyl# gives aradical anion which dimerises to give "73#[ X!ray crystallography shows that the compound "73#"with Ar�mesityl# has short C0Li and short B0Li distances[ The reaction of "74^ Ar�1\2\4\5!tetramethylphenyl# "see 5[02[0[0[2"iii## with ButLi gives "75# "Equation "02## in which there is againan L!aryl interaction ð89AG"E#0929Ł[

(84)

B

BLi

TMSTMS

TMSTMS

Li


B

BB

TMS

TMS

(85) (86)

B

B

B

But

Li

TMS

TMSButLi, ∆(13)

"iii# One Si\ one Ge\ one B and one metal function[ Also two Ge\ one Si and one metal function[ Alsotwo Ge\ one B and one metal function[ Also Two B\ one Si and one metal function[ Also two B\one Ge and one metal function

Very few examples of compounds containing these functions seem to have been prepared[ Com!pounds containing such functions should\ however\ be available from synthetic routes describedabove in this section[ In particular\ such functions should be available from the reactions betweensuitably substituted lithium reagents and appropriate metal halides[

The reaction of "76^ R�Pri1N# with two equivs[ of potassium gives "77^ M�K\ R�Pri

1N# inwhich the ring carbons can be considered to have B1KSiC substitution ð75AG"E#0001Ł[ The relatedlithium complex "77^ M�Li\ R�But# can be prepared in a similar way "Equation "03##\ althoughits actual structure is a {sandwich| with four lithium atoms between two puckered rings and acomplicated coordination pattern between the 3 Li\ 1 B and 1 ring carbon atoms ð75AG"E#0000Ł[

+ 2MRB BR

TMS

TMS

RB BR

TMS

TMS

::

2–

2M+

(87) (88)

R = NPri2, M = K

R = But, M = Li

(14)

5[02[0[2 Methanes Bearing Two Metalloid and Two Metal Functions

5[02[0[2[0 Two Si and two metal functions

The reaction between lithium vapour and "TMS#1CCl1 gives "TMS#1CLi1 in 15) yield as deter!mined by reaction with D1O ð73CC0553Ł[ The dilithium reagent is also produced\ together with"TMS#1CH1\ on the thermolysis of "TMS#CHLi at 059>C ð77PO1912Ł[ A more practical synthesis of"TMS#1CLi1 is from the reaction between "TMS#1CCl1 and four equivs[ of LiDBB "DBB�3\3?!di!t!butylbiphenyl#[ Relatively little synthetic work seems to have been done with this interestingdilithium reagent but it has been shown to react with Me2SnCl to give "TMS#1C"SnMe2#1 ð77TL4126Łand it is likely that it would react with other metal halides to give further novel Si1M1C substitutedcompounds[

The reaction of "36# "Scheme 09# with Me2SnCl not only gives compounds containing the CSi1B1

function but also the CSi1Sn1 function "see 5[02[0[0[2"iii## ð78AG"E#670\ 78AG"E#673Ł[ For a furtherexample of a compound containing the CSi1Li1 function\ see the CSi1BLi containing structure "72#ð89AG"E#0921Ł[

The di!Grignard reagent "TMS#1C"MgBr#1 may be prepared in several ways "Scheme 02#\ the bestprobably being the route using just Mg metal and the halomethane[ This route gives a yield of about


59) but the di!Grignard reagent is rather unreactive towards electrophiles and gives relatively lowyields of ditin compounds "presumably via halogen exchange# "TMS#1C"SnMe2#"SnMe1X# "X�Clor Br# when treated with Me2SnCl ð78TL5084Ł[ The low reactivity of the di!Grignard reagent isthought to be due to the shielding of the carbanionic centre by the four relatively bulky groups"1×TMS and 1×MgBr"THF#1# attached to it when crystallised from THF:hexane ð81JA6291Ł[

(TMS)2CBr2 + Mg (TMS)2C(MgBr)2 Mg/Hg + (TMS)2CBr2

(TMS)2CCl2 + MgBr2 + LiDBB DBB = ButBut

Scheme 13

The Al1Si1C species "78# and "89# are both predicted to have planar geometries at carbon and tobe stable in the gas phase or in an inert matrix[ It is not clear\ however\ how such unusual speciescould be prepared ð80CC0425Ł[

Si

Al Al

Si

(89)

Si

Al Si

Al

(90)

The reaction between "TMS#1CBrLi and Me1SnCl1\ Me1SiCl1\ or Me1GeBr1 in a 1 ] 0 ratio givesthe cyclobutane species "80# in 19\ 25 and 06) yields respectively[ Although the mechanism offormation of these rings was thought to be via a series of transmetallation steps\ more recent worksuggests that the doubly bonded species "TMS#1C1MMe1 which dimerise readily in a head!to!tailfashion may well be the source of the rings[ Acyclic species "81# and "82# are formed in the tin caseby treatment with Br1 and MeLi "Scheme 03# ð63JA5126\ 65JOM"005#146Ł[

Me2M MMe2

TMSTMS

TMS TMS

(91)

SnMe2

TMS

TMSTMS

TMS

BrMe2Sn Br

(92)

SnMe2

TMS

TMSTMS

TMS

Me3Sn

(93)

Br2

M = Sn

i, MeLiii, H2O

M = Sn

Scheme 14

The reaction between "TMS#1CCl1 and Me2SnLi in THF gives "TMS#1C"SnMe2#1 in 65) yield[Further reaction of this ditin compound with MeLi in THF gives the potentially useful lithiumreagent "TMS#1"Me2Sn#CLi which reacts with silylchlorides to give Si2SnC functions and could\ nodoubt\ be used to attach the "TMS#1"Me2Sn#C group to a variety of metals thus increasing thenumber of Si1SnMC functions known ð76CC0072\ 77JOM"244#22Ł[ The ditin compound is also formedin 12) yield as one component of a complicated mixture formed from the reaction of "Me2Sn#3Cwith one equiv[ of MeLi followed by one equiv[ of TMSCl ð74JOM"180#068Ł[

Treatment of "TMS#1"BrMe1Sn#CBr with PhLi at −009>C in Et1O a}ords "TMS#1"BrMe1Sn#CLiwhich readily eliminates LiBr to give the highly reactive unsaturated "TMS#1C1SnMe1^ this di!merises to give the distannacyclobutane in good yield ð80AG"E#82Ł[

The major product from the reaction between "TMS#1CClLi and HgCl1 is not the expected""TMS#1CCl#1Hg\ but the Hg1Si1C functional species "83# "27) yield# which is presumably formedfrom the desired product via transmetallation reactions ð69JOM"12#250Ł[

A transition metal complex "84# containing a carbon substituted by two silicon and two tungsten


atoms is formed in low yield in the reaction between WCl3 and Na:Hg in DME followed bytreatment with three equivs[ of "TMS#1NLi[ The mechanism by which "84# is formed is unknownð77POL1938Ł[

(94)

Hg Hg

TMSTMS

Cl

TMSTMS

ClTMS TMS

(95)

Me2Si

TMS-N

WW W

W

N-TMS

Me2Si

SiMe2

N-TMSTMS-N

SiMe2

NSiMe2

NSiMe2TMS TMS

5[02[0[2[1 Two Ge and two metal functions

There do not appear to be any compounds containing this function known but they could\ nodoubt\ be prepared in similar ways to the analogous Si1M1C containing species described above in5[02[0[2[0[

5[02[0[2[2 Two B and two metal functions

The CB2Sn substituted compound C"B"OMe#1#2SnPh2 rapidly undergoes base!catalysed dis!proportionation to give a high yield of C"B"OMe#1#1"SnPh2#1 together with C"B"OMe#1#3[ This typeof disproportionation occurs even more readily for the lead analogue and only C"B"OMe#1#1"PbPh2#1is isolated in attempts to prepare C"B"OMe#1#2PbPh2 ð58JA5430\ 62JOM"46#120Ł[ The propane!diolboronic esters "85# react with BuLi to give lithium compounds "86# which react with metalhalides Ph2MCl to give compounds "87# containing M1B1C functions in good yields "Scheme 04#[The lithium reagents "86# could presumably be used to prepare a wider range of M1B1C functionsby treatment with various metal halides ð62JOM"46#120Ł[

O

O

BPh3MC

3

(96)

BuLi

O

O

B

2

(97)

Li

Ph3M

Ph3M'Cl

O

O

B

2

(98)

Ph3M

Ph3M'

M = M' = Sn, 84%; M = M' = Pb, 39%; M = Sn, M' = Pb, 79%

Scheme 15

Addition of ButLi to the unsaturated boron species "88# leads to formation of a dilithium salt in49) yield which x!ray crystallography shows to have a diboraallene structure "099# in the solidstate "Equation "04## ð77AG"E#0269Ł[ The dilithium reagent has been used to prepare several othercompounds containing multiply bonded boron atoms ð89AG"E#288Ł[


ButLiMes B •

Mes

TMS

TMS

–

Li+ B

But But

BMes Mes

LiOEt2Et2OLi

(99) (100)

(15)

The reaction between a dilithium reagent and two equivs[ of Me2SnCl "Equation "05## a}ords aB1Sn1C substituted species "Ar�mesityl\ 82) Ar�1\2\4\5!Me3C5H\ 87)#[ Presumably treatmentof the dianion with other metal halides would lead to further B1M1C containing compoundsð78AG"E#673Ł[

B

Ar

Li

B

TMS

TMS

LiAr

(47)

+ 2Me3SnClB

B SnMe3

SnMe3TMS

TMS

Ar

Ar

+ 2LiCl (16)

Ar = 2, 4, 6-Me3C6H2, 93%Ar = 2, 3, 5, 6-Me4C6H, 98%

Treatment of the dianion "49# with Ph2PAuCl gives compounds "40# in 11) yield\ containingboth B1Si1C and Au1B1C groupings "see 5[02[0[0[2"iv## which seem to have been formed via a silylmigration and a geminal substitution ð75AG"E#0001\ 78CB0770Ł[

Calculations on the B1Li1C functional compound "090# have shown that a planar coordinationat C is energetically preferable to a tetrahedral con_guration but the compound does not seem tohave been made ð65JA4308\ 76T0908Ł[

(101)HB BH

LiLi

5[02[0[2[3 Other combinations of two metalloids and two metal functions

There are very few\ if any\ compounds known containing mixed metalloids and two metalfunctions[ However\ they should be available by the routes described above for related compoundscontaining two of the same metalloid[

5[02[0[3 Methanes Bearing One Metalloid and Three Metal Functions

5[02[0[3[0 One Si and three metal functions

The main component of the mixture formed on treating "Me2Sn#3C with MeLi followed by oneequiv[ of TMSCl is "Me2Sn#2CTMS\ but this does not seem to have been isolated as a pure compoundð74JOM"180#068Ł[ A similar lead compound\ "Me2Pb#2CTMS\ is formed in the reaction between"Me2Pb#2CLi "see 5[02[1[1# and TMSCl ð80SA"A#738Ł[ Reactions between the lead substituted lithiumreagent and other halosilanes would no doubt allow a range of "Me2Pb#2CSiR2 compounds to beprepared[

The reaction between trihalomethanes and Co1"CO#7 gives trinuclear complexes containing m2!carbyne ligands\ e[g[\ "091# in Equation "06#[ This reaction can be extended to include silyl substitutedtrihalomethanes^ thus\ Me1SiHCCl2\ TMSCX2 "X�Cl or Br#\ or PhMe1SiCCl2 react with Co1"CO#7to give complexes "091# "R0R1R2�Me1OH "after some hydrolysis in the workup#\ Me2 and PhMe1#ð62JOM"49#154\ 68JOM"067#116Ł[ Unfortunately\ silyltrihalomethanes are di.cult to make and an alter!native route to the carbyne species is to treat methylidyne or bromomethylidyne tricobalt!nonacarbonyl complexes with silanes R0R1R2SiH as shown by the general Equation "06# ð66JA4198\


68JOM"067#116\ 70JOM"110#146Ł[ The route using the m2!CH species is probably the better one as it doesnot generate HBr which can cause unwanted side reactions such as Si0Ph bond cleavage at thesilicon[ Once formed\ the complexes "091# can undergo a variety of reactions at silicon withoutdisrupting the cluster framework thus enabling a wider range of compounds to be easily preparedð66JA4198Ł[

(102)

+ R1R2R3SiH + HX (17)

X = H or Br

(CO)3CoCo(CO)3

Co(CO)3

X

(CO)3CoCo(CO)3

Co(CO)3

SiR1R2R3

The reaction of silicon hydrides that are themselves within a transition metal complex withHCCo2"CO#8 has also given compounds containing an SiCo2C grouping "see Scheme 05#ð81JOM"326#212Ł[

Fe

Fe

SiR2H

SiR2H

Fe

SiR2HSiR2CCo3(CO)9

Fe

SiR2CCo3(CO)9

SiR2CCo3(CO)9

HCCo3(CO)9

R = Me or Ph

R = Me, Et or Ph

Scheme 16

Cobalt bridged carbyne complexes of the type shown above in Equation "06# undergo metalsubstitution reactions giving mixed metal clusters as shown in Scheme 06[ Alternatively\ mixedmetal clusters may be prepared from mixed metal carbyne clusters "Scheme 06# ð89JOM"270#150Ł[

Scheme 17

M = Mo or W

Et3SiH

+ NaMCp(CO)3(CO)3Co

Co(CO)3

Co(CO)3

SiEt3

(CO)3CoCo(CO)3

MCp(CO)2

SiEt3

(CO)3CoCo(CO)3

MCp(CO)2

The cobalt mediated cleavage of alkynes and concomitant build!up of clusters seems to be ageneral reaction and a wide range of compounds have been prepared using this type of methodology[Thus various alkynes and dialkynes react with either "h4!C4H4#Co"CO#1 or "h1!C1H3#1Co"h4!C4H4#to give tricobalt cluster species containing m2!CSiMe2 ligands as outlined in Equation "07#ð70JOM"106#094\ 71JOC2081\ 75OM283Ł[ Such reactions are clearly complicated and often give low yieldsof the compounds shown in Equation "06# together with numerous other products although\ insome cases\ the intermediates may be isolated and fully characterised[


TMS

TMS

CoCpCpCoCo

Cp

CpCo

TMS

TMS

TMS

TMS

CoCpCpCoCo

Cp

TMS

TMS

CoCpCpCoCo

Cp

TMS

CoCpCpCoCo

+ CpCo(CO)2

Cp

(18)

TMS

n-decane

reflux

+ +

The reaction between CpCo"CO#1 and TMSC2CC2CTMS gives structure "092# ð68JA1657Ł[The hexametallic complexes "093# rearrange on ~ash vacuum pyrolysis at 449>C to give the isomers"094# containing two m2!CTMS ligands "Equation "08## ð72JA0273Ł[

(103)

CoCpCpCoCo

Cp

TMS

TMS

CoR1R1CoCo

R1 ∆

R1CoCo

R1

SiR23

SiR23

CoR1R1CoCo

R1

SiR23

CoR1R1CoCo

R1

SiR23

(104) (105)

R2 = Me R1 = η5-C5H5

R2 = Me R1 = η5-MeC5H4

R2 = Et R1 = η5-C5H5

(19)

CoR1

Cluster formation also occurs when nickelocene is treated with alkyllithium reagents[ ThusTMSCH1Li gives the carbyne bridged cluster "095# and "096# "if excess lithium reagent is used# as ablackÐviolet solid in 04) yield which may also be obtained from the reaction between nickeloceneand the nickel alkyl complex "097# "Scheme 07# ð68JOM"067#260Ł[

The bimetallic asymmetrically bridging alkylidyne complex "098# reacts with low valent transitionmetal fragments to form a range of trimetallic species\ "009#\ "000# and "001# in good yield containinga m2!CSiPh2 ligand which bridges three di}erent transition metals "Scheme 08# ð77JOM"244#120Ł[


NiPh3P

TMSTMS Li

CpNiNiCp

NiCp

TMS

TMS Li

Cp2Ni + BunLi, RT

NiNiCp

NiCp

TMS

(107)

(108)

Cp2Ni +

(106)

TMS

excess

Scheme 18

Scheme 19

CpCOWPt(PPri

3)

CuCl

SiPh3

OC

CpCOWCO

Pt(PPri3)

SiPh3

Cp(CO)2WFe(CO)3

Pt(CO)(PPri3)

SiPh3

Fe2(CO)9Et2O

(112)

CuCl Fe2(CO)9

Et2O/CO

(110) (109) (111)

CpCOWFe(CO)3

Pt(PPri3)

SiPh3

OC

5[02[0[3[1 One Ge and three metal functions

Germanes\ R2GeH\ react in a similar way to the silanes discussed above in 5[02[0[3[0 with themethylidyne cluster HCCo2"CO#8 to give germyl substituted methylidynes[ For example\ germanesPh2GeH\ MePh"0!naphth#GeH\ Et2GeH\ Bun

2GeH\ Et1ClGeH and "PhCH1#1ClGeH all give theappropriate R2GeCCo2"CO#8 species with structure similar to the silicon analogues "091# above"Equation "06## ð66JA4198\ 68JOM"067#116\ 79JOM"077#218\ 70JOM"110#146Ł[

5[02[0[3[2 One B and three metal functions

There seem to be few compounds known containing this type of function although they may beavailable by treatment of a methylidyne cluster with R1BH species in the same way that the silyland germyl substituted carbyne complexes described above are made[

5[02[1 METHANES BEARING FOUR METAL FUNCTIONS

5[02[1[0 Methanes Bearing Four Similar Metals

Calculations on the structures of CLi3 and C"BeH#3 have been carried out in order to ascertainwhether the small electropositive substituents might promote planar rather than tetrahedralgeometry at carbon[ In both cases tetrahedral geometry is still preferred ð65JA4308Ł[

The synthesis of CLi3 may be achieved in several ways[ The original synthesis involved the reactionof CCl3 with lithium vapour at 649>C giving a 39[4) yield as determined by deuterolysis to giveCD3 ð72JOM"138#0Ł[ More convenient and apparently higher yielding syntheses involve the reaction

394Four Metal Functions

between C"HgEt#3 and ButLi or those between C"HgCl#3 and either ButLi or lithium metalð73AG"E#884Ł[ Tetralithiomethane reacts in a variety of complicated ways with simple derivatisingagents and its synthetic use is therefore probably limited[

The tetrastannylmethane "Me2Sn#3C is formed as a readily sublimable solid from the reactionbetween Me2SnLi and either CHCl2 or CCl3 in THF ð64OMS"09#07\ 73JOM"155#26Ł[ The compound hasalso been prepared enriched in 02C at the central carbon by use of ð02CŁCCl3 in a similar reactionð68JOM"061#182Ł[ The reaction between CCl3 and four equivs[ of Me2SnNa a}ords only 07)"Me2Sn#3C at room temperature but 30) if carried out at −12>C ð65JOM"011#060Ł[ The reactionbetween "Me2Sn#3C and one equiv[ of MeLi followed by one equiv[ of Me2PbCl a}ords a mixtureof tetrametallomethanes including a very low yield of "Me2Pb#3C ð74JOM"180#068Ł[ The tetra!stannylmethane also reacts with various electrophilic reagents to give other substituted Sn3C com!pounds as a result of cleavage of the Sn0Me bonds only ð73JOM"155#26Ł[ The reaction between fourequivs[ of Ph2PbLi and CCl3 a}ords the stable crystalline solid "Ph2Pb#3C[ The compound issparingly soluble in organic solvents and only decomposes at 181Ð183>C ð54RTC32Ł[

The reaction of ethanol in alkaline solution with mercuric oxide gives a species C1Hg5"OH#5known as {ethane hexamercarbide|[ This material dissolves in aqueous solutions of carboxylic acidsto give crystalline compounds C"HgOCOR#3 "R�Me or CF2# which have been characterised byx!ray crystallography and which react with MeSH in H1O to give C"HgSMe#3 ð63CC535\ 66ZN"B#0911Ł[Tetramercuriomethanes may also be prepared from C"B"OMe#1#3 by treatment with various mercurycompounds[ Thus\ reactions with Hg"OAc#1 and with EtHgOAc a}ord C"HgOAc#3 and C"HgEt#3respectively ð69JA120\ 73AG"E#884Ł[ Reactions between the acetate C"HgOAc#3 and HF\ halide orcyanide ions gives the compounds C"HgX#3"X�F\ Cl\ Br\ I\ or CN# ð67JOM"042#0\ 68ZN"B#289\73AG"E#884Ł[

5[02[1[1 Methanes Bearing Three Similar and One Different Metal Function

The reaction between "Me2Sn#3C and one equiv[ of MeLi followed by one equiv[ of Me2PbCla}ords a mixture of tetrametallomethanes including "Me2Sn#2CPbMe2 and "Me2Pb#2CSnMe2 inyields of 33 and 7) yields respectively[ Unfortunately\ although the yield of the PbSn2C compoundis reasonable\ it is likely to be di.cult to separate such a mixture and the reaction is\ therefore\ oflittle synthetic use ð74JOM"180#068Ł[ The lithium reagent "Me2Sn#2CLi may be observed by NMRspectroscopy from the reaction between "Me2Sn#3C and MeLi in Et1O ð70JMR"33#43Ł[ A similar lead!substituted methyllithium "Me2Pb#2CLi may be prepared by treating "Me2Pb#2CH with MeLi inTHF ð80SA"A#738Ł in the same way as "TMS#2CLi is prepared from "TMS#2CH "5[02[0[1[0"i#"a##[The lead substituted compound could presumably be used in the same way as the silicon substitutedlithium reagent to prepare a wide variety of compounds containing the "Me2Pb#2C group by reactionwith suitable metal or metalloid halides[

5[02[1[2 Methanes Bearing Two Similar and Two Different Metal Functions

The reaction between "Me2Sn#3C and one equiv[ of MeLi followed by one equiv[ of Me2PbCla}ords a mixture of tetrametallomethanes including a 15) yield of "Me2Pb#1C"SnMe2#1ð74JOM"180#068Ł[

5[02[1[3 Methanes Bearing Four Different Metal Functions

Although there are a potential 024640 di}erent combinations "and their optical isomers# of 32di}erent metals at a tetrahedral carbon centre very few seem to have been prepared[ A comprehensivesearch of the literature for such a large number of functional groups is clearly very di.cult to carryout\ and it is quite possible that many such groupings have been missed in compiling this chapter[It is hoped that omission of such groupings will not be serious for the organic chemist[


5[02[2 METHANES BEARING MORE THAN FOUR METALLOID OR METALFUNCTIONS

The structures of magnesium ð80AOC"21#036Ł\ lithium ð74AOC"13#243Ł and Na\ K\ Rb\ or Csð76AOC"16#058Ł compounds are usually complicated in the solid state often having carbon with acoordination number greater than four[ Such species will not be further described here and are fullydiscussed in the reviews referred to[

There are a variety of carboranes known in which the cage carbons have a metal or metalloidsubstituent[ Such compounds usually contain carbon with a formal coordination number greaterthan four and are\ therefore\ strictly outside the coverage of this section\ however a few representativecompounds are given below[ The reaction between C1B09H01 with BuLi a}ords "002# which reactswith various mercury salts to give compounds of type "003# "Equation "19## ð56JOM"6#274\ 57BAU303\62JGU737Ł[ Such compounds will not be discussed further here but they have been the subject ofseveral reviews "see for example\ ð89AOC"29#88\ 81CRV114\ 81CRV140Ł and references therein#[

2RHgCl

(113)

BHBH

BH

BH

BHBH

HB

BH

BH

Li

Li

(114)

BHBH

BH

BH

BHBH

HB

BH

BH

HgR

HgR

(20)

Carbon may have six!coordinate octahedral geometry in complexes containing dicationic ionssuch as in "004# formed according to Equation "10#[ Such compounds may be characterised by x!ray crystallography and the central carbon observed by ð02CŁCNMR spectroscopy ð77AG"E#0433\80AG"E#0377Ł[

(115)

AuL

C

AuLLAu

LAu

AuL

AuL(21)C[B(OMe)2]4 + 6LAuCl + 6CsF 6CsCl + 2B(OMe)3 + [MeOBF3]–

2

2+

L = Ph3 or Ph2(p-Me2NC6H4)P


6.14Functions Containing aCarbonyl Group and at LeastOne HalogenGEOFFREY E. GYMER andSUBRAMANIYAN NARAYANASWAMIPfizer Central Research, Sandwich, UK

5[03[0 CARBONYL HALIDES WITH TWO SIMILAR HALOGENS 397

5[03[0[0 Carbonic Di~uoride\ COF1 3975[03[0[0[0 From carbonic dichloride "phosène# 3985[03[0[0[1 From carbon monoxide 3985[03[0[0[2 Oxidative methods 3095[03[0[0[3 Other methods 309

5[03[0[1 Carbonic Dichloride "Phosène#\ COCl1 3005[03[0[1[0 Phosène toxicity 3005[03[0[1[1 Handlin` phosène 3005[03[0[1[2 Preparation of phosène*an overview 3015[03[0[1[3 Laboratory methods suitable for preparin` phosène 3015[03[0[1[4 Other laboratory preparations of phosène 3025[03[0[1[5 Puri_cation of phosène 3035[03[0[1[6 Preparation of isotopically labelled phosène 3035[03[0[1[7 Phosène alternatives 304

5[03[0[2 Carbonic Dibromide\ COBr1 3065[03[0[3 Carbonic Diiodide\ COI1 307

5[03[1 CARBONYL HALIDES WITH TWO DISSIMILAR HALOGENS 307

5[03[1[0 One Fluorine and Chlorine\ Bromine or Iodine Function 3075[03[1[0[0 Carbonic chloride ~uoride\ COClF 3075[03[1[0[1 Carbonic bromide ~uoride\ COBrF 3195[03[1[0[2 Carbonic ~uoride iodide\ COFI 319

5[03[1[1 One Chlorine and Bromine or Iodine Function 3195[03[1[1[0 Carbonic bromide chloride\ COBrCl 3195[03[1[1[1 Carbonic chloride iodide\ COClI 310

5[03[1[2 One Bromine and One Iodine Function 3105[03[1[2[0 Carbonic bromide iodide\ COBrI 310

5[03[2 CARBONYL HALIDES WITH ONE HALOGEN AND ONE OTHER HETEROATOM FUNCTION 310

5[03[2[0 One Haloèn and One Oxyèn Function 3105[03[2[0[0 Fluoroformate esters\ ROCOF 3115[03[2[0[1 Preparation of chloroformate esters\ ROCOCl 3135[03[2[0[2 Preparation of bromoformate esters\ ROCOBr 3205[03[2[0[3 Preparation of iodoformates\ ROCOI 320

5[03[2[1 One Haloèn and One Sulfur Function 3205[03[2[1[0 Fluorothiolformate esters\ RSCOF 3215[03[2[1[1 Chlorothiolformate esters\ RSCOCl 3235[03[2[1[2 Bromothiolformate esters\ RSCOBr 3255[03[2[1[3 Iodothiolformate esters\ RSCOI 326

396

397 Carbonyl Group and at Least One Haloèn

5[03[2[2 One Haloèn and One Nitroèn Function 3265[03[2[2[0 Carbamoyl ~uorides\ R0R1NCOF\ and other N!~uorocarbonyl compounds 3265[03[2[2[1 Carbamoyl chlorides\ R0R1NCOCl\ and other N!chlorocarbonyl compounds 3315[03[2[2[2 Carbamoyl bromides\ R0R1NCOBr\ and other N!bromocarbonyl compounds 3415[03[2[2[3 Carbamoyl iodides\ R0R1NCOI 343

5[03[2[3 One Haloèn and One Phosphorus Function 3435[03[2[3[0 Chlorocarbonyl derivatives of phosphorus"III# 3435[03[2[3[1 Chlorocarbonyl derivatives of phosphorus"V# 343

5[03[2[4 One Haloèn and One As\ Sb or Bi Function 3445[03[2[5 One Haloèn and One Metalloid "B\ Si or Ge# Function 3445[03[2[6 One Haloèn and One Metal Function 344

5[03[2[6[0 Halocarbonyl complexes of _rst transition series metal "iron and chromium# 3445[03[2[6[1 Halocarbonyl complexes of second transition series metals "ruthenium and rhodium# 3455[03[2[6[2 Halocarbonyl complexes of third transition series metals "rhenium and iridium# 346

5[03[0 CARBONYL HALIDES WITH TWO SIMILAR HALOGENS

Compounds of formula X1C1O\ where X�F\ Cl\ Br or I\ are currently named in ChemicalAbstracts as carbonic dihalides[ Other names commonly applied to these compounds are carbonyldihalides\ carbonyl halides and halophosgenes[ The latter derives from the historical name phosgene\which is still the term most commonly used to describe carbonic dichloride[

Methods of synthesis have been previously reviewed^ the review by Hagemann ð72HOU"E3#0Ł isparticularly important because it also covers the remit of Section 5[03[1 and includes some pre!parative details[ This area is covered comprehensively in Beilstein up to the end of 0879[ By far themost important member of this class is carbonic dichloride\ which will henceforth be referred to byits more common name\ phosgene[ Phosgene is an important industrial chemical used mainly in themanufacture of polyurethanes and polycarbonates[ Although the organization of this section retainsthe logical sequence by commencing with discussion of the synthesis of carbonic di~uoride in Section5[03[0[0\ it may be prudent of the reader also to take note of some aspects discussed in Section5[03[0[1\ concerning the preparation and safe handling of phosgene\ and possible ways of avoidingits use[

5[03[0[0 Carbonic Di~uoride\ COF1

Carbonic di~uoride\ also called carbonyl di~uoride and ~uorophosgene\ is a stable\ colourlessgas\ b[p[ −72>C[ It is commercially available from several suppliers^ the industrial preparationprobably involves the reaction of carbon monoxide with elemental ~uorine[ In common with allcarbonyl dihalides\ it is extremely toxic[ In addition\ hydrolysis and other nucleophilic attack leadsto the formation of hydrogen ~uoride\ with all its attendant hazards[ The suitability of glassapparatus for the preparation or reaction of carbonic di~uoride should be carefully considered[ Ifsigni_cant quantities of hydrogen ~uoride could be generated during the reaction or work!upprocedure\ then failure of glass apparatus may occur with potentially disastrous results[ Gaseousproducts can be freed of hydrogen ~uoride by passage through a copper tube packed with sodium~uoride pellets ð59IS044Ł[ Glass is inert to pure carbonic di~uoride[

Three prinicipal routes to carbonic di~uoride have been described\ together with several mis!cellaneous preparations "Scheme 0#[

COCl2

COF2

Cl3COCOClCO

BrXCF2 (X = Cl, Br)F3C

F F

F

NaFor Et3N•3HF

or NH4FNH4F

SO3RuO4 (cat.)

AgF2

Scheme 1

NaOCl

⟨79JFC(13)175⟩ ⟨ 75GEP2261108⟩

⟨60IS(6)155⟩ ⟨84JAP8439705⟩

⟨62JA4275⟩⟨80JFC(15)423⟩

⟨71GEP2105907⟩

398Two Similar Halo`ens

5[03[0[0[0 From carbonic dichloride "phosgene#

Transhalogenation of phosgene with various ~uorine donors is a well!described method ofpreparing carbonic di~uoride[

The early work of Steinkopf and Herold led to the preparation of impure carbonic di~uoride inlow yield[ They achieved this by warming a mixture of arsenic tri~uoride and phosgene ð19JPR68Ł[Emele�us and Wood devised a substantially improved procedure using antimony tri~uoride^ theyobtained carbonic di~uoride of 89Ð84) purity\ free from hydrogen chloride\ from which it cannotbe separated by distillation ð37JCS1072Ł[ This method was further re_ned by Haszeldine and Iserson\who added chlorine to the mixture to form pentavalent antimony salts\ allowing them to obtaincarbonic di~uoride of 84) purity in 79Ð74) yield ð46JA4790Ł[ These reactions were performed atquite high pressures and temperatures\ and these methods were superseded by the work of Tullockand co!workers\ who were able to prepare carbonic di~uoride of 84) purity in 69Ð79) yieldthrough the reaction of phosgene and sodium ~uoride in acetonitrile at 29Ð24>C and atmosphericpressure ð51JA3164\ B!64MI 503!90Ł[ This is an excellent preparative method\ only equalled by thealternative of Franz\ who has used the triethylamine trishydrogen ~uoride complex and phosgenein acetonitrile at room temperature to give carbonic di~uoride in quantitative yield\ containingcarbon dioxide as the only impurity ð79JFC"04#312Ł[ A similar method employing ammoniumhydrogen ~uoride as the ~uorine source is also reported to give carbonic di~uoride in 89) yield\together with 7) carbonic chloride ~uoride ð60GEP1094896Ł[ Another potentially useful route in!volves substitution of trichloromethyl chloroformate for phosgene using similar reaction con!ditions\ thus avoiding to some extent the dangers associated with the handling of phosgeneð73JAP7328694Ł[ Because of the extreme toxicity of phosgene\ alternatives are described in Section5[03[0[1[7[

Two gas phase reactions leading to carbonic di~uoride are worthy of mention\ since they can berun as continuous ~ow procedures\ suitable for industrial production[ In the _rst\ thionyl ~uoride"from thionyl chloride and sodium ~uoride# and phosgene are passed as a 3 ] 0 mixture over iron"III#chloride at 399>C to give carbonic di~uoride in 85) yield ð79EGP028825Ł[ Many other catalysts havebeen examined\ and the SOFCl and SOCl1 formed during the reaction can be recycled by treatmentwith NaF to regenerate thionyl ~uoride[ The second method involves the preparation of carbonicchloride ~uoride by passing phosgene over calcium ~uoride at 199Ð449>C\ and then passing it overactivated carbon\ when metathesis to carbonic di~uoride and phosgene takes place ð77EUP142416Ł[In these last two preparations it should be borne in mind that at the elevated temperatures employed\phosgene is at least partly dissociated to carbon monoxide and chlorine\ and thus ~uorination ofcarbon monoxide may be the predominant reaction pathway[

Finally\ Glemser and Biermann have prepared carbonic di~uoride in quantitative yield by passinga 0 ] 0 mixture of phosgene and nitrogen tri~uoride through a nickel tube heated to 399>C ð56CB1373Ł[These workers were fully aware that ~uorination of carbon monoxide produced by thermal de!composition of phosgene could explain the reaction course observed[ The same workers have shownthat ~uorination of CO with NF2 does in fact yield COF1 in nearly quantitative yield ð56CB0073Ł[

5[03[0[0[1 From carbon monoxide

The ~uorination of carbon monoxide with elemental ~uorine is probably the preferred methodof production of carbonic di~uoride on an industrial scale\ since it is amenable to continuous ~owtechnology ðB!78MI 503!90Ł[ As with many reactions employing elemental ~uorine\ this does notappear to be a straightforward process ð23ZAAC"110#043Ł^ however\ it had already been found to besatisfactory as a preparative procedure by the 0839s ð33MI 503!90\ B!52MI 503!90Ł[ In the latterpreparation\ carbon monoxide is actually burnt in an atmosphere of electrolytically generated~uorine\ and Kwasnik refers to the risk of violent explosion if the procedure is incorrectly conducted[This method has now been improved by introducing carbon monoxide into the liquid HF electrolyteused for the ~uorine preparation ð69JAP6915500Ł[ The purity of the COF1 produced is apparentlyimproved when potassium ~uoride is added to the electrolyte ð58USP2350949Ł when COF1 is the soleproduct[

A well!described laboratory procedure by Tullock and co!workers exists for the ~uorination ofcarbon monoxide by a more amenable method[ Carbon monoxide and helium are mixed togetherand passed through a copper tube containing silver"II# ~uoride[ An exothermic reaction ensues\ togive COF1 contaminated with HF\ which is removed by passing the e/uent gases through sodium~uoride pellets[ Upon condensation\ the COF1 is obtained in 69Ð74) yield and greater than 88)


purity[ This method avoids the low!temperature fractional distillation usually necessary to obtainpure product ð59IS044Ł[

Fluorination of carbon monoxide with sulfur hexa~uoride under the in~uence of IR radiationhas also been claimed as a simultaneous preparation of carbonic di~uoride and sulfur tetra~uorideð70CZP197140Ł[ A less attractive but high!yielding method involves passing an equimolar mixture ofcarbon monoxide and NF2 through a nickel tube heated to 349Ð419>C\ to give COF1 in 89Ð84)yield based on NF2 ð56CB0073Ł[ NF2 is prepared by electrolysis of molten ammonium ~uoridehydro~uoride\ so this is not normally an accessible laboratory method ð55CB260Ł[

Olah and Kuhn prepared carbonic di~uoride as a pure side!product in 50) yield when in pursuitof carbonic bromide ~uoride by the exothermic reaction of bromine tri~uoride with carbonmonoxide ð45JOC0208Ł[ This method is well described\ but is probably unacceptably hazardousðB!52MI 503!90Ł[

5[03[0[0[2 Oxidative methods

Oxidation of terminal 0\0!di~uoroalkenes*in practice usually per~uoroalkenes*leads to car!bonic di~uoride[ One method stands out as being particularly suitable for laboratory use\ namelycatalytic ruthenium tetroxide oxidative cleavage[ Commercially available per~uoropropene can beoxidized by a catalytic quantity of ruthenium tetroxide in Freon 002 with gradual addition ofperacetic acid\ periodic acid or sodium hypochlorite to regenerate the catalyst[ The products areTFA and COF1\ both in high yield ð68JFC"02#064Ł[ It is reasonable to speculate that if tetra!~uoroethylene was used in the reaction\ the sole product would be COF1\ possibly constituting avery simple and controllable small!scale laboratory preparation[ Oxidation of tetra~uoroethylenewith oxygen at 199Ð349>C has been used as a very high!yielding industrial preparationð54NEP5498407Ł\ which can be made more controllable by dilution with Freons ð63URP313798Ł[Carbonic di~uoride is also produced in quantitative yield from per~uoropropene and oxygen underIR radiation\ in the presence of SF5 as a radiation absorber ð89CZP153247Ł[

Terminal 0\0!di~uoroalkenes can also be ozonised to give carbonic di~uoride with high impliedyields^ however\ this has not yet been developed as a synthetic route to COF1 ð79JA6461\ 78BAU0469Ł[Finally\ carbonic di~uoride can be prepared by oxidation of chloro! or bromodi~uoromethane withoxygen at 199Ð499>C\ a method suitable for an industrial ~ow process ð78EUP209144Ł[

5[03[0[0[3 Other methods

The reaction of ~uorohalomethanes with sulfur trioxide provides a versatile route to allcarbonic ~uoride halides[ Carbonic di~uoride is thus available by reaction of either dibro!modi~uoromethane or bromochlorodi~uoromethane with SO2[ The presence of catalysts such assulfuric acid or mercury"I# or mercury"II# salts is bene_cial\ and is in fact necessary for e.cientreaction of the second substrate[ In this manner\ dropwise addition of dibromodi~uoromethane toSO2 at 24Ð33>C gave 52) carbonic di~uoride based on starting material consumed ð63GEP1150097Ł[The scope of this reaction in fact extends beyond that encompassed above\ as will be demonstratedin subsequent sections of this chapter\ making it probably the most general laboratory methodavailable[

Fluorination of carbonyl sul_de also provides a route to carbonic di~uoride[ When carbonylsul_de is passed through a copper tube packed with cobalt tri~uoride maintained at 199>C\ thee/uent gases comprise only COF1 and SF5\ which are readily separated by low!temperature frac!tionation ð41JA4681Ł[ In a second example\ carbonyl sul_de diluted with helium is introduced intoan electrolyte consisting of sodium ~uoride in anhydrous hydrogen ~uoride[ Electrolysis producescarbonic di~uoride\ 70)\ and sulfur hexa~uoride\ 88) ð65JAP6529923Ł[

Lastly\ in a patent to the Dow Chemical Company\ heating a mixture of calcium ~uoride\ titaniumdioxide and carbon at 1799Ð2499>C under argon gives rise to carbonic di~uoride as the only volatileproduct[ This industrial process uses very cheap starting materials which may compensate for thelarge of amount of energy consumed^ it can be operated continuously\ and various other ~uoridesources and oxides are also satisfactory ð56USP2211712Ł[


5[03[0[1 Carbonic Dichloride "Phosgene#\ COCl1

Named in Chemical Abstracts as carbonic dichloride\ COCl1 is more commonly known as phos!gene[ Other commonly encountered names are carbonic acid dichloride\ carbonyl dichloride andcarbonyl chloride[ It is an important building block for the chemical industry[ It is a colourless gas\b[p[ 7>C\ of legendary toxicity ðB!82MI 503!90Ł[ In 0877 the consumption of phosgene in the USAalone was 0[5×098 pounds "6[2×097 kg#\ of which approximately 89) was absorbed by themanufacturers of polyurethane plastics ðB!78MI 503!90Ł[ It is thus widely available\ and is suppliedeither as a liqui_ed gas in a pressurized cylinder\ or in solution\ most commonly as a 19) by weightsolution in toluene[

A comprehensive review of the methods of preparation of phosgene would not in the authors|opinion be of great value since the vast majority of methods are of no synthetic importance^phosgene is so widely available and so toxic that its preparation in the laboratory should be severelyquestioned[ Exceptions to this are the production of minute quantities of isotopically labelledmaterial\ which are covered in detail later in this section[ Instead the authors intend to devote partof this section to informing readers on the safe use of phosgene and its replacement by less hazardousalternatives[

Phosgene preparation has been reviewed up to the end of 0814 ð19JCS0309\ 16CRV098Ł[ Subsequentreviews relating to phosgene appear to pay little attention to its synthesis ð71KO"06#305\ 72HOU"E3#0Ł[This is not surprising since the current method of phosgene manufacture has been known since 0767ð0767G122Ł[

5[03[0[1[0 Phosgene toxicity

In order to handle phosgene in a safe manner\ an appreciation of its toxicity is necessary[ Phosgeneis an insidious poison[ The initial e}ects of irritation to the eyes and mucous membranes oftendisappear upon removal from exposure^ however\ within 13 h\ pulmonary oedema\ due to lungtissue acylation\ commonly develops[ This is often fatal[ At high exposures "×199 ppm#\ phosgenecan pass into the blood\ and death from congestive heart failure follows[ From animal and\ moresadly\ human experiments the following generalization emerges] LC49 "lethal concentration to 49)of recipients#�469 ppm min[ This implies that 09 ppm exposure for 0 h or 099 ppm for 5 minwould exceed the LC49[ In the event of phosgene exposure\ the casualty should be at once removedfrom exposure\ kept warm and rested[ Arti_cial respiration and external cardiac massage should beemployed where necessary[ Mouth to mouth resuscitation can be employed without undue risk tothe operator[ Removal of contaminated clothing and copious irrigation of the skin and eyes withwater are also necessary[ In all cases the casualty should be removed to hospital and kept underobservation[ Medical treatment may involve corticosteroids\ administration of oxygen and othersymptomatic measures ðB!82MI 503!91Ł[

5[03[0[1[1 Handling phosgene

Phosgene should always be used in a fume hood with powerful extraction[ Two persons shouldbe present during the entire period that exposure could occur[ A method of monitoring phosgeneconcentration is advisable[ A simple method is to tape phosgene indicator papers to the fume hoodsill[ These are prepared by soaking _lter papers in a 09) alcoholic solution of equal parts ofp!dimethylaminobenzaldehyde and diphenylamine\ and allowing to dry[ These yellow papers turndeep orange in the presence of dangerously high concentrations of phosgene ðB!78MI 503!91Ł[ ADraeger pump speci_c for phosgene is a more sophisticated safeguard[ Reactions quite often requirean excess of phosgene\ or fail to proceed\ in both cases leaving residual phosgene at the end of theexperiment[ This must be purged from the reaction mixture by a vigorous stream of nitrogen\ thee/uent gas being scrubbed with sodium hydroxide solution[ Phosgene may still be present after thisoperation\ so reaction solvent subsequently evaporated o} should also be freed from phosgenebefore being discarded[ This could be achieved by addition of a reactive amine or alcohol\ whichwould convert any remaining phosgene to a urea or carbonate[

Several excellent alternatives to phosgene have been developed^ these will be reviewed in Section5[03[0[1[7[ However\ sometimes phosgene provides the simplest\ cleanest way of accomplishing adesired reaction[


5[03[0[1[2 Preparation of phosgene*an overview

Phosgene was _rst prepared by the interaction of chlorine and carbon monoxide in the presenceof sunlight\ by John Davy "the brother of Sir Humphrey Davy# in 0701 ð19JCS0309Ł[ The nameis derived from two Greek words meaning {light| and {I produce|[ By 0767\ Paterno� replacedphotoinduction by passing the gases over active carbon in the form of animal charcoal ð0767G122Ł[This method is still employed today for the manufacture of billions of kilograms of phosgene eachyear[ Currently the process is run at 49>C and 4Ð09 atm in the presence of activated carbon toproduce phosgene at a cost of less than 49 cents per pound\ or 14 cents per kilogram ðB!78MI 503!90Ł[ In 0758 the only other preparation to have withstood the test of time was discovered bySchu�tzenberger ð0758BSF087Ł[ This involves reaction of carbon tetrachloride with sulfur trioxide[The reaction is conveniently done in oleum\ a solution of sulfur trioxide in sulfuric acid ð08CR"058#06Ł[Armstrong reported that hexachloroethane also produced phosgene under the same conditionsð0769CB629Ł[ It was also discovered that the use of sulfuric acid without the addition of sulfurtrioxide still led to the production of phosgene ð16CRV098Ł[ The oleum process was used to producephosgene in Italy during the First World War\ but could not compete with the continuous catalyticprocess discovered by Paterno� [ Many other methods have been developed\ often alternative waysof combining chlorine and carbon monoxide\ with chlorine present as a metallic chloride ð17G332\29CB0110Ł or nonmetallic chloride such as SCl1 ð57FRP0415847Ł[ Many catalysts have also beenconsidered as alternatives to activated carbon in the Paterno� process ð71MI 503!90Ł[ Several methodsinvolving the oxidation of chloroform or carbon tetrachloride were also developed\ using oxygenð13MI 503!90Ł or chromium reagents ð0782CB0889Ł[ Pyrolysis of various compounds containingchlorine\ carbon and oxygen has also often led to the production of phosgene\ notably oxalylchloride\ which when heated in a sealed vessel at 239>C for 69 h gave phosgene in quantitative yieldtogether with carbon monoxide ð02CB0315Ł[ A more recent example involves the decomposition oftrichloroacetic acid at 299Ð399>C ð61URP234983Ł[ Other substrates were also pyrolysed to givephosgene in this patent[

5[03[0[1[3 Laboratory methods suitable for preparing phosgene

Should the laboratory preparation of phosgene be undertaken\ great care must be taken that safehandling practices are adopted[ It is well to remember that the most hazardous part of any processis often the dismantling of apparatus and disposal of residues[ The reader is urged to consult Section5[03[0[1[1[ Some examples are shown in Scheme 1[

Scheme 2

COCl2

Cl3COCOClCO

Cl

Cl Cl

Cl

SO3 or H2SO4

CCl4

Cl2, Bun3PO

O2, hν

Active carbon or pyridine

⟨79JOC3573⟩

⟨88JAP88319205⟩

⟨82JAP8292513⟩⟨85JOC715⟩

⟨52HOU(8)84⟩⟨B-56MI 614-01⟩

"i# Preparation of phos`ene from carbon tetrachloride and sulfuric acid

In this method\ carbon tetrachloride is dropped into 099) sulfuric acid containing 1) by weightignited kieselguhr maintained at 019Ð029>C[ The evolved phosgene is absorbed into toluene\ inwhich it is extremely soluble\ whilst the hydrogen chloride produced passes through ðB!45MI 503!90Ł[


"ii# From carbon tetrachloride and oleum

This method is essentially that of Grignard and Urbain ð08CR"058#06Ł^ however\ it is moreaccessible through Houben!Weyl ð41HOU"7#73Ł[ When 34) oleum is heated to 67>C and treateddropwise with carbon tetrachloride\ phosgene is evolved\ which is passed through sulfuric acid andcollected "81)#[

"iii# From trichloromethyl chloroformate\ Cl2COCOCl

The use of trichloromethyl chloroformate as a phosgene alternative will be dealt with in detailin Section 5[03[0[1[7[ However\ dropwise addition of trichloromethyl chloroformate to carbontetrachloride containing a trace of pyridine gives\ after 29 min\ 89) conversion to phosgene\ withno chloroformate remaining ð71JAP7181402Ł[ The authors suggest that the less carcinogenic solventdichloromethane should be substituted for carbon tetrachloride in this preparation[

A solution of trichloromethyl chloroformate in THF is also rapidly decomposed to phosgene bythe addition of activated charcoal ð74JOC604Ł[

5[03[0[1[4 Other laboratory preparations of phosgene

Four methods follow which are possibly suitable for the small!scale preparation of phosgene[Three of these are less attractive because of special conditions employed "irradiation\ pressure# orlack of detail[ The fourth is a demonstration experiment designed for educational purposes andmay not be of synthetic utility[

"i# Phosphine oxide!catalysed reaction of chlorine and carbon monoxide

Workers at the Ube Chemical Industries Company have published a series of patents in whichphosgene is produced in high yield "×89)# by the phosphine oxide! or sul_de!catalysed reactionof chlorine with carbon monoxide under pressure in carbon tetrachloride\ tetrachloroethane\ chlo!robenzene or dichlorobenzene ð67GEP1700209\ 79JAP79025004\ 79JAP79051304Ł[ An example of this workhas appeared in a more accessible source ð68JOC2462Ł[ This reaction was carried out under a pressureof 4 kg cm−1 of carbon monoxide with tri!n!butylphosphine oxide as a catalyst[

"ii# From paraformaldehyde\ carbon tetrachloride and aluminum trichloride

Carbon tetrachloride\ paraformaldehyde and aluminum chloride in the mole ratio 0 ] 9[4 ] 9[4 werewarmed together at 24Ð39>C for 1Ð1[4 h\ then heated under re~ux for 9[4Ð0 h to give phosgene inquantitative yield after careful decomposition with ammonium hydroxide ð57ZPK0279Ł[ The quantityof ammonium hydroxide used is obviously crucial\ since phosgene reacts rapidly with ammonia[

"iii# Photochemical oxidation of tetrachloroethylene

Air or oxygen is bubbled through tetrachloroethylene whilst irradiation is carried out using lightwith a wavelength of 199Ð189 nm[ This method is claimed to be very controllable and capable ofproducing phosgene in high yield ð77JAP77208194Ł[

"iv# Oxidation of chloroform or carbon tetrachloride usin` a platinum metal catalyst

In experiments designed to demonstrate the preparation\ quanti_cation and reactions of phosgene\chloroform or carbon tetrachloride is oxidised with oxygen in the presence of platinum metal[ Theresulting phosgene is assayed by reaction with sodium iodide and titration\ and converted to crystalviolet dye with dimethylaniline and aluminum chloride ð67MI 503!90Ł[


5[03[0[1[5 Puri_cation of phosgene

Phosgene from cylinders is approximately 88) pure\ the remainder comprising of carbon mon!oxide\ carbon dioxide\ air\ hydrogen chloride and water[ Laboratory phosgene prepared by someroutes may also contain chlorine[ Glemser suggests that evaporation of 19) of the volume ofphosgene at room temperature and pressure\ and low!temperature vacuum distillation\ with frac!tionation of the remainder leads to a very pure product ðB!52MI 503!91Ł[ Chlorine in phosgene canbe detected by bubbling the gas through mercury[ Discolouration indicates the presence of chlorine\which can be removed by passage through two washbottles containing cottonseed oil ð52OSC"3#413Ł[A suitable method for removing bromine from carbonic bromide ~uoride involves passing the gasthrough irradiated trichloroethylene ð62AG"E#807Ł[ This method may also be suitable for removingchlorine from phosgene[

5[03[0[1[6 Preparation of isotopically labelled phosgene

Only phosgene labelled at the carbon atom with 00C\ 02C or 03C will be covered in this section\although other phosgenes labelled at oxygen and chlorine are known[ The authors feel that labellingat carbon is the most relevant\ particularly for the preparation of labelled drug molecules\ which isthe major use of labelled phosgenes[

"i# Carbon!00!labelled phos`ene

Two European groups have prepared 00C!labelled phosgene by several routes\ resulting in di}erentspeci_c activities[ This isotope is a positron emitter with a half!life of only 11 min and is valuablefor the study of interactions of drug molecules with receptors by positron emission tomography\and for nuclear medicine imaging[ It is obviously necessary to prepare and use the ð00CŁCOCl1rapidly\ and all methods use ~ow techniques to sequentially execute the various steps involved[Early work employed bombardment of nitrogen by a cyclotron proton beam in the presence ofoxygen to produce either ð00CŁCO ð67MI 503!91Ł or ð00CŁCO1 ð66MI 503!90\ 67MI 503!92Ł by the nuclearreaction 03N"pa#00C[ The latter was then reduced by zinc at 399>C to ð00CŁCO[ The ð00CŁCO wasthen either photochemically united with chlorine ð67MI 503!91\ 70MI 503!90Ł\ or chlorinated overplatininum"IV# chloride ð66MI 503!90\ 72MI 503!90Ł at 189Ð329>C to produce ð00CŁCOCl1[ By thephotolytic method\ the speci_c activity was below 099 mC mmol−0 19 min after the reactioncommenced ð67MI 503!91Ł[ This was improved to 399Ð499 mC mmol−0 by employing the pla!tininum"IV# chloride route ð72MI 503!90Ł[ However\ more recently a new route involving the pro!duction of ð00CŁCH3 by bombardment of nitrogen in the presence of hydrogen has been developed[The ð00CŁCH3 is then chlorinated by copper"II# chloride at 279>C\ and oxidized to ð00CŁCOCl1 overiron _lings ð76MI 503!90Ł[ The speci_c activity 29 min after the commencement of the process was0399Ð0599 mC mmol−0[ Many medically useful molecules have been prepared from ð00CŁCOCl1\including urea\ pimozide\ diphenylhydantoin\ dimethyloxazolidinedione and ketanserinð72MI 503!90Ł[

"ii# Carbon!02!labelled phos`ene

Great insight can be obtained into small moleculeÐenzyme interactions through 02C NMR studies[For this reason\ many 02C!labelled drug molecules have been synthesized\ and several of these haveemployed ð02CŁCOCl1 in their preparation[ Two methods of preparation have been used\ both scaled!down versions of standard phosgene preparations[

"a# From irradiation of 02CO and chlorine[ Stoichiometric amounts of chlorine and ð02CŁCO werecondensed into an evacuated ~ask and externally cooled with liquid nitrogen[ The ~ask was thenallowed to warm up and was irradiated for 2 h[ A quantitative yield of ð02CŁCOCl1 was claimed^however\ subsequent reaction gave phosgene!derived products in only 69) yield ð89MI 503!90Ł[

"b# From carbon tetrachloride and sulfuric acid[ Oleum was added dropwise to 87) sulfuric aciduntil a yellow colour persisted\ to give 099) sulfuric acid[ A small quantity of freshly ignited Celitewas added\ followed by ð02CŁCCl3[ The mixture was heated to 039>C\ and the ð02CŁCOCl1 evolvedwas collected in dry toluene cooled in an iceÐsalt bath\ whilst the hydrogen chloride produced was


allowed to escape through a calcium chloride drying tube[ Although the gain in weight of toluenesuggested almost quantitative conversion to ð02CŁCOCl1\ subsequent reaction with methanol gavephosgene!derived products in only 59) yield ð76MI 503!91Ł[

"iii# Carbon!03!labelled phos`ene

In all recent applications ð03CŁCOCl1 has been purchased from one of the established sources[However\ the methods used above for the preparation of ð00CŁCOCl1 and ð02CŁCOCl1 should also besuitable for ð03CŁCOCl1\ starting from ð03CŁCO1\ ð03CŁCO\ ð03CŁCH3 or ð03CŁCCl3[ An early preparationof ð03CŁCOCl1 from ð03CŁCO and chlorine by UV irradiation has been reported ð37JA0857Ł[

5[03[0[1[7 Phosgene alternatives

There has been rising pressure to avoid the use of isocyanates\ and their precursor phosgene\ inrecent years[ Since over 89) of world consumption of phosgene is in the preparation of isocyanatesfor polyurethane manufacture\ and a further 6) is destined for polycarbonate production\ if theseplastics could be formed by alternative routes the use of phosgene worldwide would virtually cease[As will be discussed later in this section\ the majority of phosgene alternatives suitable for thepreparation of _ne chemicals are not only expensive\ but are generally derived from phosgene[ Forproductions purposes\ the alternatives must be cheap and must be prepared in a manner whichavoids the use of hazardous reagents[ The candidate which ful_ls these criteria is dimethyl carbonate\prepared from methanol\ oxygen and carbon monoxide in the presence of a copper catalyst at lessthan ,0 per pound ",1 per kilogram#[ A discussion on the replacement of phosgene by dimethylcarbonate\ and on other nonphosgene routes to isocyanates\ carbonates and urethanes was publishedin 0878 ðB!78MI 503!90Ł[ Several laboratory alternatives to phosgene will now be discussed[

"i# Trichloromethyl chloroformate "diphos`ene#\ Cl2COCOCl

All compounds bearing the 0OCCl2 leaving group are potential phosgene sources\ and thisshould be borne in mind during their use and subsequent disposal[ Under many reaction conditions\trichloromethyl chloroformate reacts with nucleophiles in such a way that the phosgene formedduring the _rst acylation step is destroyed by a second molecule of the nucleophilic species at amore rapid rate than the original attack on trichloromethyl chloroformate^ thus\ 9[4 mol of thereagent is equivalent to 0[9 mol of phosgene\ the latter being present only in minute concentrationduring the reaction[ This leads to its common name\ {diphosgene| "Scheme 2#[ However\ there areseveral circumstances which lead to rapid and total conversion of trichloromethyl chloroformate intophosgene[ These include high temperature ð0776JPR88Ł or contact with iron"III# oxide ð08JPC387Ł\activated charcoal ð74JOC604Ł or pyridine ð71JAP7181402Ł[ It must be assumed that many othercommonly encountered substances will also catalyse this transformation[ Thus\ trichloromethylchloroformate\ b[p[ 017>C\ is a stable and easy to handle alternative to phosgene^ it is widely andcommercially available\ or readily prepared by chlorination of methyl chloroformate ð68OS"48#084Ł[In many transformations\ yields are comparable to those achieved with phosgene^ however\ in someinstances signi_cantly lower yields are reported ð79JOC3948Ł[ In a paper on the preparation of chiraloxazolidinones\ Pridgen et al[ list many applications for which trichloromethyl chloroformate hasproved satisfactory ð78JOC2120Ł[ The authors suggest that whilst the use of this reagent will normallybe much less hazardous than the use of phosgene\ the same high standard of safety precautionsmust be taken since there is a risk that considerable and unexpected concentrations of phosgenemay be present during and after reaction[

Cl O Cl

ClCl O

Nu Cl

O

Cl Cl

O

Nu

Nu Cl

O

Scheme 3

Nu

+ Cl–++ +RO Cl

O

2Cl–+2

2 Nu•HCl2 ROH


"ii# Bis"trichloromethyl# carbonate "triphos`ene#\ Cl2COCO1CCl2

The use of bis"trichloromethyl# carbonate as a phosgene alternative is a logical extension of thework described above[ This compound is a stable crystalline solid\ m[p[ 70Ð72>C\ commerciallyavailable\ or readily prepared by chlorination of dimethyl carbonate ð76AG"E#783Ł[ It has theadvantage as a solid of being easy to weigh\ thus simplifying quantitative additions[ As might bepredicted\ 0 mol of reagent is equivalent to 2 mol of phosgene\ although in practice this stoichiometrydoes not always lead to maximum yields "Scheme 3#[ Whilst no speci_c references to the extensivedecomposition of bis"trichloromethyl# carbonate to phosgene have been discovered\ its similarityto trichloromethyl chloroformate strongly suggests that the same safety precautions should beemployed[

Nu

O

Cl3CO O Cl

ClCl Nu

O

NuOCl

ClCl

Cl– + O

Cl

Cl

Cl

Cl

O

Nu

Cl– + +O

Cl+Nu+

Cl

Cl

O

Nu2 Nu

O

Cl+Nu

Scheme 4

3 + 3 Cl–

O

ClRO3 + 3 Nu•HCl

3 ROH

+

Eckert and Forster have described a range of applications for bis"trichloromethyl# carbonate\encompassing most of the reactions commonly achieved by phosgene[ The yields achieved withstrictly stoichiometric quantities of triphosgene range from 57) to 83) ð76AG"E#783Ł[ Subsequently\its use in the preparation of N!carboxyanhydrides of a!amino acids ð77TL4748Ł\ a!chloro!chloroformates ð78TL1922Ł and quinazolinediones ð80SC174Ł\ all in good yields\ has been reported[

"iii# N\N?!Carbonyldiimidazole

N\N?!Carbonyldiimidazole "0# appears an excellent substitute for phosgene when its role is toinsert a carbonyl function between two nucleophilic groups to complete a _ve! or six!memberedring[ The nucleophilic groups can be amines\ enamines\ alcohols\ enols\ thiols or enethiols\ and theheterocycles formed may be either aromatic or nonaromatic^ the examples are numerous\ and theyields normally high[ This application is exempli_ed by formation of the cyclic carbonate from cis!cyclohexane!0\1!diol in 83) yield ð64SC36Ł\ and by benzimidazolones from o!phenylenediaminesat room temperature ð45AG643\ 54JHC30Ł in yields of 79Ð89)[ The use of phosgene to performthis ring closure often requires high temperatures[ Examples of most other transformations morecommonly employing phosgene are also reported for carbonyldiimidazole^ a brief selection follows[

NN

NN

O

(1)

Symmetrical and unsymmetrical ureas can be prepared by reaction with a single amine ð45AG643Ł\or sequentially with two di}erent amines ð80JOC780Ł[ Carbamates can result from sequential reaction


with an alcohol and an amine ð80JOC780Ł[ Aldoximes are converted into nitriles in quantitative yieldð71SC14Ł[ Isocyanates may be prepared from amines in good yield ð50AG55Ł[ By preparing thebismesylate salt of carbonyldiimidazole\ formamides can be dehydrated to isonitriles ð71JCR"S#68Ł[

"iv# Carbonates as phos`ene alternatives

The role of dimethyl carbonate as an industrial substitute for phosgene has already been alludedto[ Such relatively unactivated molecules are used in laboratory synthesis\ but the reaction conditionsare often quite harsh^ for example\ 2!aminoalkanols and diethyl carbonate give high yields of thecyclic carbamates in the presence of sodium methoxide at 019>C ð79LA011Ł[ Many more activatedcarbonates have been developed[ Commercially available N\N?!disuccinimidyl carbonate "1# is avery useful reagent^ a recent example of sequential reaction with complex alcohols and a complexamine to give good yields of carbamates by workers from Merck\ Sharp + Dohme is worthy ofmention ð81TL1670Ł[ Bis"1!pyridyl# carbonate "2# also performs similar reactions\ and has beenexploited by the same workers to form carbamates[ In this case\ even tertiary alcohols give excellentyields providing the alkoxide salt is used ð80TL3140Ł[ Examples of high!yielding ring formation bycarbonyl insertion have also been reported for this reagent ð75H"13#0514Ł[ Ueda et al[ report thatN\N?!"carbonyldioxy#bisbenzotriazole "3# may have similar utility ð72S897Ł[

O

O ON N

O O

OO(2)

O

O O

(3)

N N

O

O ON N

(4)

NN N

N

"v# Chloroformates as phos`ene alternatives

The role of tricholoromethyl chloroformate as a phosgene substitute has already been discussed[Several other chloroformates also ful_l this role[ Amongst these\ commercially available 3!nitro!phenyl chloroformate is very useful[ The mixed carbonates formed by its reaction with alcohols areoften stable to ~ash chromatography\ yet are su.ciently reactive to form carbamates with aminesat room temperature ð81EUP375837Ł[ Further applications of 3!nitrophenyl chloroformate and sev!eral other bifunctional chloroformates have been reported ð82S092Ł[

5[03[0[2 Carbonic Dibromide\ COBr1

Carbonic dibromide\ also commonly called bromophosgene\ carbonyl bromide and carbonyldibromide\ is a colourless liquid\ b[p[ 54Ð56>C ð62T2298Ł[ It is stable in the absence of light at−09>C^ however\ at higher temperature or in the presence of light\ dissociation into bromine andcarbon monoxide takes place[ For this reason\ relatively little has been published on its preparationand reactions[ The _rst synthesis of pure carbonic dibromide was carried out by von Bartal in 0894ð95LA"234#223Ł[ It is to his credit that the yield and purity of COBr1 produced by his method havenot been signi_cantly improved[ The most accessible description of this preparation is that reportedby Fodor and co!workers ð62T2298Ł[ Carbon tetrabromide was melted and heated to 014>C\ andconcentrated sulfuric acid was added dropwise\ with vigorous stirring[ The crude distillate was freedfrom bromine by the passage of ethylene[ Redistillation gave pure carbonic dibromide in 57) yield[Storage of this material\ even at low temperature\ is not advisable\ since any decomposition canlead to a buildup of pressure because of the formation of carbon monoxide[ As with all the carbonichalides\ the extreme toxicity of carbonic dibromide dictates that all procedures should be carriedout in a fume hood with good extraction[

Several other preparations of carbonic dibromide have been attempted[ The thermal decompo!sition of oxalyl bromide at 049Ð044>C with subsequent cooling of the autoclave to −79>C beforeopening has been reported to give carbonic dibromide in a distilled yield of 19) ð02CB0315Ł[Attempts to prepare carbonic dibromide by passing carbon monoxide over heated bromides of


platinum and gold led only to evolution of bromine\ presumably by dissociation of carbonicdibromide at the elevated temperatures used ð29CB0110Ł[ Finally\ carbon tetrabromide has beenoxidised photochemically to carbonic dibromide by molecular oxygen in the presence of bromineas a sensitizer ð26CB0979Ł[ This experiment was not designed to be of synthetic utility\ but mightwarrant further investigation[

5[03[0[3 Carbonic Diiodide\ COI1

The preparation of carbonic diiodide has never been successfully demonstrated[ Theoreticalcalculations of its thermodynamic properties ð71MI 503!91Ł and of its electronic structure ð89MI 503!91Ł have been reported[ The dissociation temperature of carbonic dibromide is approximately−09>C ð62T2298Ł\ and for carbonic ~uoride iodide\ below −19>C ðB!52MI 503!90Ł^ thus\ carbonicdiiodide would be expected to dissociate at temperatures well below this[ Attempted preparationfrom carbon monoxide and platinum tetraiodide led to liberation of iodine at 024>C\ well belowthe thermal decomposition temperature of platinum tetraiodide[ This probably indicates the for!mation and instantaneous dissociation of carbonic diiodide ð29CB0110Ł[ In a less brutal series ofexperiments\ Staudinger and Anthes concluded that the dissociation temperature of carbonic di!iodide was below −79>C ð02CB0315Ł[ This result was based on the formation of iodine by thereaction of oxalyl chloride and sodium iodide at low temperature[

5[03[1 CARBONYL HALIDES WITH TWO DISSIMILAR HALOGENS

5[03[1[0 One Fluorine and Chlorine\ Bromine or Iodine Function

5[03[1[0[0 Carbonic chloride ~uoride\ COClF

Carbonic chloride ~uoride is a stable\ colourless gas\ b[p[ −36>C[ In company with all othercarbonic dihalides\ it is extremely toxic[ The production of hydrogen ~uoride on hydrolysis is anadded risk[ Some suggestions concerning the safe handling of this class of compounds can be foundin Section 5[03[0[1[1[

Other names which have been used for this compound are carbonyl chloride ~uoride\ carbonylchloro~uoride\ chlorocarbonyl ~uoride and chloro~uorophosgene[ It is not commercially available^however\ it is of some importance in the synthesis of ~uoroformates\ which are a valuable class ofintermediates[

Several methods are available for its preparation "Scheme 4#[

COClF

COCl2

COCl2

SO3

Cl3CF

COCl2

COCl2 COCl2

ClF

Cl2CFH

COF2 SOF2

SiF4or NF3

O2, e–

CO, –18 °C

SbF3or AsF3or CaF2

∆

HF

∆

⟨73CB1752⟩

⟨73AG(E)918⟩⟨74GEP22611088⟩⟨B-75MI 614-01⟩

⟨B-63MI 614-01⟩

⟨51MI 614-01⟩

⟨48JCS2183⟩⟨63JOC1639⟩

⟨88EUP253527⟩

⟨46JA1672⟩

⟨80EGP139936⟩

⟨64JOC3007⟩⟨67CB2484⟩

Scheme 5

308Two Dissimilar Haloèns

"i# From carbonic dichloride "phosène#

The _rst successful preparation of carbonic chloride ~uoride was by Emele�us and Wood\ whoheated phosgene with antimony tri~uoride in a 3 ] 0 molar ratio\ with the addition of some antimonypentachloride\ at 024>C for 0 h[ The condensed product was puri_ed by low!temperature distillation\and was isolated in 69) yield ð37JCS1072Ł[ Upon repeating this work\ Haszeldine and Isersonreported a purity of 84)\ with carbon dioxide as the major contaminant ð46JA4790Ł[ In an extensionof this work\ Christie and Pavlath substituted arsenic tri~uoride for antimony tri~uoride\ achievinga yield of over 89) ð54JOC0528\ 72HOU"E3#0Ł[ An industrial gas phase process has also been patentedby ICI in which phosgene is passed over calcium ~uoride at 199Ð449>C to give carbonic chloride~uoride as the major product ð77EUP142416Ł[ Several nonmetallic ~uorinating agents have also beensuccessfully employed[ Christie and Pavlath passed a 0 ] 0 molar ratio of phosgene and silicontetra~uoride through a quartz tube heated at 319>C to give carbonic chloride ~uoride in quantitativeyield\ with more than 39) conversion at a single pass ð53JOC2996Ł[ Glemser and Biermann obtainedcarbonic chloride ~uoride in 54) yield by passing nitrogen tri~uoride and phosgene in a 0 ] 1 molarratio through a metal tube heated at 209>C[ The only other product formed was carbonic di~uoride\with 71) conversion of phosgene[ Higher temperatures led exclusively to carbonic di~uorideð56CB1373Ł[ Finally\ by an industrial gas phase process it is claimed that the reaction of thionyl~uoride with phosgene over a Lewis acid catalyst at 299Ð399>C can be made to yield either carbonicdi~uoride or carbonic chloride ~uoride by varying molar ratios and conditions[ The thionyl ~uoridecould be regenerated by reaction of the sulfur!containing by!products with sodium ~uorideð79EGP028825Ł[ Carbonic chloride ~uoride has also been prepared in 49) yield by reaction ofphosgene with anhydrous hydrogen ~uoride at 79>C ð35JA0561Ł[

"ii# From sulfur trioxide and ~uorotrichloromethane

Preparations of carbonic chloride ~uoride from phosgene inevitably involve either gas streams\usually at high temperature\ or the use of pressure vessels[ For this reason\ its production from~uorotrichloromethane and oleum or sulfur trioxide is much more suitable for laboratory use[ Fourminor variations of this method are reported by Siegemund\ giving yields from 59) to 72)[ Thereaction appears quantitative\ but total conversion of the perhalogenomethane is not achieved[The highest yield resulted from slow treatment of sulfur trioxide with ~uorotrichloromethaneð62AG"E#807Ł^ however\ methods involving oleum may be more simple to carry out ð62AG"E#807\63GEP1150097\ B!64MI 503!90Ł[

"iii# From carbon monoxide and chlorine mono~uoride

Carbonic chloride ~uoride is formed in 74Ð89) yield by the combination of excess carbonmonoxide and chlorine mono~uoride at −07>C ðB!52MI 503!90Ł[ Small quantities of carbonicdi~uoride and phosgene are also formed in this reaction\ but can readily be removed by low!temperature distillation[

"iv# Metathesis from carbonic di~uoride and phosène

During experiments designed to prepare various perhalomethanes\ Haszeldine and Iserson fre!quently found carbonic chloride ~uoride amongst the products isolated from the co!pyrolysis ofcarbonic di~uoride and phosgene over carbon powder at temperatures of 399Ð349>C ð46JA4790Ł[Subsequently\ Ja�ckh and Sundermeyer have proposed this as a convenient synthetic method\claiming a 29) yield of carbonic chloride ~uoride from heating a 0 ] 0 molar ratio of phosgene andcarbonic di~uoride ð62CB0641Ł[ Unfortunately\ no details are given^ however\ in laboratories usedto the safe handling and distillation of gases\ this preparation\ which uses two commercially availablestarting materials\ may be worth pursuing[


"v# By photochemical oxidation of dichloro~uoromethane

A mechanistic investigation of the chlorine sensitised photochemical oxidation of dichloro!~uoromethane by molecular oxygen has been reported by Schumacher ð40MI50390Ł[ Whilst notsuitable as a preparative method in this form\ the high yield "84)# could prove attractive tolaboratories equipped to carry out photochemistry on a synthetic scale[

5[03[1[0[1 Carbonic bromide ~uoride\ COBrF

Carbonic bromide ~uoride is a stable\ colourless gas\ b[p[ −10>C[ It is also commonly calledbromo~uorophosgene\ carbonyl bromo~uoride and carbonyl bromide ~uoride[ It must be assumedto have the high toxicity associated with all phosgene analogues[ Carbonic bromide ~uoride hasbeen prepared by two methods[

"i# From bromine tri~uoride and carbon monoxide

Bromine tri~uoride is maintained at a temperature between 7>C and 29>C whilst a stream ofcarbon monoxide is passed through it[ This process must be carefully controlled\ since brominetri~uoride solidi_es at 7>C\ and the exothermic reaction can become explosive above 29>C[ Frac!tional condensation separates the carbonic bromide ~uoride from carbonic di~uoride\ which isformed in an equimolar amount[ Redistillation gives pure carbonic bromide ~uoride in 74) yieldð45JOC0208\ B!64MI 503!90Ł[ A minor variation of this preparation is reported to give COBrF in greaterthan 89) yield ðB!52MI 503!90Ł[

"ii# From tribromo~uoromethane and sulfur trioxide

Slow addition of tribromo~uoromethane to sulfur trioxide at 39>C yields carbonic bromide~uoride "53)#\ contaminated with a considerable amount of sulfur dioxide[ This method alsoproduces an equimolar amount of bromine\ which can be removed by passing the evolved gasesthrough irradiated trichloroethylene before condensation ð62AG"E#807\ 63GEP1150097Ł[

5[03[1[0[2 Carbonic ~uoride iodide\ COFI

Carbonic ~uoride iodide is a colourless gas\ b[p[ −19[5>C ðB!52MI 503!90Ł or ¦12[3>C ðB!64MI503!90Ł[ The great discrepancy between the two reported boiling points may be due to the instabilityof this rarely reported compound[ Above −19>C\ decomposition occurs with the liberation ofiodine[ The only published synthesis involves the agitation of iodine penta~uoride under 019 atmpressure of carbon monoxide for 6 d[ The major products are carbonic di~uoride and iodine^however\ carbonic ~uoride iodide can be isolated in 01) yield by low!temperature distillation atreduced pressure ðB!52MI 503!90\ B!64MI 503!90Ł[

5[03[1[1 One Chlorine and Bromine or Iodine Function

5[03[1[1[0 Carbonic bromide chloride\ COBrCl

Carbonic bromide chloride is a colourless gas\ b[p[ 24Ð26>C\ _rst prepared by Besson in 0784 bythe reaction of phosgene with boron tribromide at 049>C ð0784BSF333Ł[ Von Bartal repeated thiswork ð95LA"234#223Ł\ and also reported a preparation from phosgene and aluminum tribromideð96MI 503!90Ł[ The only other published account of the synthesis of this compound is by Garino\ whoclaimed that carbonic bromide chloride is formed by aerial oxidation of chlorobromoiodomethaneð15G736Ł[

310One Halo`en

5[03[1[1[1 Carbonic chloride iodide\ COClI

Carbonic chloride iodide has never been reported\ and\ by extrapolation from the stabilities ofother carbonic dihalides\ its decomposition temperature would be considerably below −19>C[

5[03[1[2 One Bromine and One Iodine Function

5[03[1[2[0 Carbonic bromide iodide\ COBrI

Carbonic bromide iodide has also never been reported\ and would be expected to be unstable attemperatures considerably below −19>C[

5[03[2 CARBONYL HALIDES WITH ONE HALOGEN AND ONE OTHER HETEROATOMFUNCTION

5[03[2[0 One Halogen and One Oxygen Function

Carbonyl halides with one halogen and one oxygen function are named in Chemical Abstracts asesters of the respective carbonohalidic acid^ however\ they are almost universally referred to ashalogenoformates in the chemical literature\ and this nomenclature will be adopted in this section[Other names sometimes encountered\ and exempli_ed by ethyl chloroformate\ are ethyl car!bonochloridate\ ethyl chloroformic ester\ ethoxycarbonyl chloride and ethyl chlorocarbonate[ Thefree parent halogenoformic acids are unknown\ but their esters are generally stable[ Chloroformatesare important in the preparation of many _ne chemicals\ particularly carbamates\ which are com!monly used as amine!protecting groups in peptide chemistry[ Fluoroformates are also used toprepare such carbamates\ especially when the oxygen substituent is a tertiary alkyl group\ wherethe improved thermal stability relative to the corresponding chloroformate is an advantage[ Onepotentially valuable attribute of ~uoroformates is their stability in dipolar aprotic solvents such asDMF and DMSO^ under these conditions\ chloroformates react exothermically to form complexproducts[ Thus\ where insolubility is a problem\ alkoxycarbonylation with ~uoroformates in a polarmedium provides an alternative[ This has been demonstrated by the protection of carbohydrates astheir carbonate derivatives ð89JOC0740Ł[ Another important use of ~uoroformates is in the con!version of alcohols to their respective ~uorides by catalysed or thermally induced loss of carbondioxide from the alcohol ~uoroformate ð44JA4922\ 54JOC3093Ł[ The carbonyl function of ~uoro!formates can also be ~uorinated with sulfur tetra~uoride to give the stable0OCF2 moiety "Scheme5# ð81GEP3912096Ł[

RF

ROCF3

–CO2

SF4

O

RO F

Scheme 6

⟨55JA5033⟩⟨65JOC4104⟩

⟨92GEP4023107⟩

The preparation of chloroformates has been comprehensively reviewed up to 0871 ð53CRV534\72HOU"E3#8Ł^ ~uoroformates have been similarly treated ðB!61MI 503!90\ 72HOU"E3#8Ł[

Bromoformates have been rarely reported\ and most aliphatic iodoformates are unstable^ someexamples of aromatic iodoformates and aliphatic iodoformates with stabilising features will bediscussed[

The sulfur analogues of haloformates and halothiolformates are also well known and are coveredin Section 5[03[2[1[ However\ the analogous sellenium and tellurium compounds have not beendescribed[


5[03[2[0[0 Fluoroformate esters\ ROCOF

Two general methods are available for the preparation of ~uoroformates^ preparations ofa!~uoroalkyl ~uoroformates and a!chloroalkyl ~uoroformates are covered separately[ The synthesisof several miscellaneous unusual ~uoroformates is also included[

"i# Preparation from alcohols or phenols and carbonic halide ~uorides

This method is not very attractive as a general laboratory method since the carbonic halide~uorides are highly toxic gases[ In addition\ only carbonic di~uoride is commercially available[Although not usually reported\ carbonates would be formed as by!products unless a large excess ofthe phosgene analogue is used[ This would not hinder isolation\ however\ which is normally carriedout by distillation[

Emele�us and Wood originally developed this method\ exploring the use of both carbonic di~uorideand carbonic chloride ~uoride in the presence of pyridine to prepare ethyl ~uoroformate and phenyl~uoroformate ð37JCS1072Ł[ It is notable in this report that whilst ethyl ~uoroformate could beprepared by merely bubbling carbonic di~uoride through a solution of ethanol and pyridine intoluene\ a similar experiment with phenol led to diphenyl carbonate in quantitative yield[ However\phenyl ~uoroformate was isolated in 49) yield when phenol and excess carbonic di~uoride wereheated in benzene solution to 099>C in an autoclave[ This suggests that in the presence of pyridine\phenyl ~uoroformate reacts much more rapidly with phenol than ethyl ~uoroformate reacts withethanol[ In reactions involving carbonic chloride ~uoride\ only ~uoroformates were formed*nochloroformates were detected[ Emele�us and Wood also state that the ~uoroformates they preparedwere more thermally stable and less rapidly hydrolysed than their chloroformate counterparts[ Apatent from Merck describes the preparation of ~uoroformates from primary and secondary alcoholsand carbonic di~uoride under pressure at 069>C ð81GEP3912096Ł[ A well!described method for thepreparation of t!butyl ~uoroformate by Ugi and Wackerle involves the generation of carbonicchloride ~uoride from ~uorotrichloromethane and oleum\ and immediate reaction with t!butanoland triethylamine in ether ð64S487Ł[ The reported yield exceeds 89)^ t!butyl ~uoroformate issu.ciently stable to be stored\ in contrast to the corresponding chloroformate\ which is stable onlyat low temperature\ rapidly decomposing to t!butyl chloride and carbon dioxide[ This compound isthus a useful reagent for amine protection[ Voelter and co!workers have also exploited the samemethod for the preparation of ~uoroformates for use as amine protecting group precursors[ Thus\Adpoc ~uoride "4# was prepared from 1!"0!adamantyl#propan!1!ol as a crystalline solid in 84)yield ð79CC0154Ł\ and t!Bumeoc ~uoride "5# as an unstable oil in 60) yield ð72LA137Ł[ Finally\ Ola�hand Kuhn have prepared alkyl ~uoroformates in good yield from primary and secondary alcoholsby reaction with carbonic bromide ~uoride ð45JOC0208Ł[ This method is technically very demanding\and in the authors| view should not be attempted[ A compilation of ~uoroformates prepared fromcarbonic dihalides up to 0868 has been published ð72HOU"E3#8Ł[

(5)

OCOF

(6)

But

But

OCOF

"ii# Preparation from chloroformates\ carbonates or carbamates and a ~uoride source

"a# From chloroformates[ In cases where the chloroformate is readily available\ several excellentmethods exist for transhalogenation to the corresponding ~uoroformate[ The early work of Gos!wami and Sarker ð22JIC426Ł\ extended by Nakanishi et al[ ð44JA2988Ł using thallium"I# ~uoride\ hasbeen superseded\ and it is recommended that this method should not be attempted[ By usingpotassium ~uoride and a catalytic 07!crown!5 phase transfer agent\ Olofson and Cuomo were ableto prepare aryl and primary and secondary alkyl ~uoroformates at room temperature in yields of79Ð84)[ Yields were diminished by conducting the exchange at elevated temperatures\ due to

312One Halo`en

catalysed decomposition of the products to ~uorides with the liberation of carbon dioxideð68JOC0905Ł[ A similar method has used tetrabutylammonium ~uoride or triethylbenzylammoniumchloride and potassium ~uoride to prepare primary and secondary alkyl ~uoroformates in yieldsranging from 31) to 81) ð71SC402Ł[ In 0875\ Japanese workers reported that a carefully driedmixture of calcium and potassium ~uorides e}ected 84) conversion of ethyl chloroformate to~uoroformate at room temperature in acetonitrile ð75CC682Ł[ These methods appear attractivebecause of their simplicity and high yields[ Other methods involving chloroformates and a ~uoridesource have also been reported ð72HOU"E3#8Ł[

"b# From 0!chloroethyl carbonates[ Olofson and co!workers have developed a very general andhigh yielding preparation of ~uoroformates by the reaction of potassium ~uoride with 0!chloroethylcarbonates of most alcohols or phenols\ catalysed by 07!crown!5 ð89JOC0736Ł[ The reaction proceedsby ~uoride attack on the carbonate to give the ~uoroformate and the 0!chloroethoxide anion\ whicheliminates chloride\ yielding acetaldehyde "Scheme 6#[ Removal of this volatile product ensures thereverse reaction does not occur[ The use of 0\1\1\1!tetrachloroethyl carbonates in this reaction alsoleads to high yields of ~uoroformates ð75EUP065031Ł[ The extra labour involved in preparing the0!chloroalkyl carbonates will in many cases be amply rewarded by the versatility of this reaction^the scope includes carbonates derived from tertiary and benzylic alcohols[

O

RO F+ MeCHOROH

O

RO O

Cl

F–

KF, 18-crown-6

O

Cl O

Cl

Scheme 7

R = n-octyl, But, Ph, PhCH2

"c# From alkyl carbamates[ Olah and Welch have devised a simple method for preparing primary\secondary and tertiary alkyl ~uoroformates in yields usually between 49) and 79) by the diazo!tisation of alkyl carbamates in commercially available pyridinium poly"hydrogen ~uoride# "Scheme7#[ Isolation is simply achieved by extraction with ether and removal of the solvent\ followed bydistillation ð63S543Ł[

O

RO F+ N2 + HF

O

RO N2+

HF

F–NaNO2, HF, pyridine

0 °C

O

RO NH2

R = Me, Pri, But

Scheme 8

"iii# Preparation of haloalkyl ~uoroformates

The reaction of carbonic di~uoride with ketones proceeds by addition of its elements across thecarbonyl group to yield a!~uoroalkyl ~uoroformates[ These can be stable compounds^ in the caseof cyclohexanone the adduct can be isolated in 67) yield as a distillable liquid[ Not surprisingly\thermal or boron tri~uoride!catalysed decomposition of these adducts yields `eminal di~uoroderivatives and carbon dioxide "Scheme 8# ð51JA3164Ł[ In a more complex manner\ reaction ofcarbonic di~uoride with DMSO yields ~uoromethyl ~uoroformate in 27) yield[ This reactionprobably proceeds by an initial Pummerer rearrangement\ but the mechanism of the subsequentsteps is not clear ð74JFC"17#108Ł[

The formation of v!chloroalkyl ~uoroformates by the reaction of carbonic chloride ~uoride with

OCOF

F

F

FO

COF2 ∆ or BF3

–CO2

Scheme 9


cyclic ethers has also been reported[ Excellent yields are obtained with oxirane\ oxetane andtetrahydrofuran in the presence of tri!n!butylamine[ Tetrahydropyran also gives the correspondingproduct\ but in much lower yield "Equation "0## ð54JOC0528Ł[ Carbonic di~uoride does not followthe same reaction course with oxirane\ instead giving 1!"tri~uoromethoxy#ethyl ~uoroformate\CF2O"CH1#1OCOF[ Larger ring sizes do not appear to have been studied ð53JOC00Ł[

F, n-Bu3NCl

O

FO

O

Cl( )

nn = 2–5

(CH2)n O (1)

"iv# Miscellaneous ~uoroformates

Tri~uoromethyl ~uoroformate\ CF2OCOF\ was formed in poor yield "04)# from the reaction ofcarbonic di~uoride with cyanogen ~uoride at low temperature[ A possible mechanism has beenproposed ð70JFC"07#148Ł[ This compound has also been prepared in high yield by the insertion ofcarbon monoxide into tri~uoromethyl hypo~uorite under photochemical conditions ð54CC130Ł[

The _nal three preparations in this section are included to exemplify unusual ~uoroformateswhich have been reported[ The authors suggest that these preparations are too hazardous to beundertaken except in laboratories where the handling of unpredictably explosive compounds isroutine[

Bis"~uoroformyl# peroxide has been studied by several groups as a radical source[ It is preparedby mixing streams of oxygen\ carbon monoxide and ~uorine in precise proportions[ Powerfulexplosions result if the conditions deviate from those reported ð61IC1420Ł[ Reaction of bis"~uoro!formyl# peroxide with a caesium ~uoride for a prolonged period at −39>C gave tri~uoromethyl~uoroformyl peroxide in 38) yield\ b[p[ −05>C[ A mechanism has been suggested ð61IC1420Ł[A low yield of the primitive ~uoroformate ~uorocarbonyl hypo~uorite can be prepared frombis"~uoroformyl# peroxide and ~uorine under UV irradiation and puri_ed by fractional distillation\m[p[ −030>C\ b[p[ −44>C ð56JA4050Ł[ Reaction of ~uorocarbonyl hypo~uorite with sulfurtetra~uoride under irradiation leads to a low yield of the unusual penta~uorosulfur ~uoroformateð56JA4050Ł[ These reactions are summarised in Scheme 09[

O2 + CO + F2F O

O

O

F

O F3CO

O F

O

FO F

O

F5SO F

OSF4, hνF2, hν

CsF

–40 °C

Scheme 10

5[03[2[0[1 Preparation of chloroformate esters\ ROCOCl

"i# From alcohols and phos`ene

Chloroformates are most commonly prepared from an alcohol or phenol and phosgene\ under avariety of conditions[ This method of synthesis has been thoroughly reviewed up to 0871ð41HOU"7#090\ 53CRV534\ 72HOU"E3#8Ł[ The authors will\ therefore\ restrict discussion to some generalcomments and recent modi_cations or extensions[ The articles cited above contain references tonumerous examples of aliphatic ð53CRV534Ł and aromatic ð53CRV534\ 72HOU"E3#8Ł chloroformatesmade by this method[ Although the use of phosgene can often be avoided by the use of variousmixed carbonates or phosgene equivalents "see Section 5[03[0[1[7#\ it is sometimes the best or mostconvenient method for the preparation of chloroformates on a laboratory scale[ Strict adherence tosafe working procedures must be practised at all times\ especially during workup procedures\ sincean excess of phosgene is often used "see Section 5[03[0[1[1#[

314One Halo`en

Primary and secondary alcohols can react with phosgene to form chloroformates in the absenceof a base[ An excess of phosgene is often employed\ which\ together with low temperatures "usuallyroom temperature or below#\ reduces the formation of carbonates formed by reaction of a furthermolecule of alcohol with the initially formed chloroformate[ On a laboratory scale\ commerciallyavailable 19) phosgene in toluene is a safe and convenient source of this reagent[ Many solventshave been used\ the only requirement being that they do not react rapidly with phosgene\ or withthe chloroformate produced[ DMF and DMSO cannot be used for this reason "see Section 5[03[2[0#^however\ high yields have been recorded in the presence of considerable concentrations of waterð63MIP50300Ł[ The use of a molar equivalent of a tertiary base\ most often triethylamine\ pyridineor dimethylaniline\ is often advantageous\ enabling the quantity of phosgene used to be reduced\and allowing reaction in the presence of acid!sensitive groups which would be otherwise destroyedby the hydrogen chloride produced as formation of the chloroformate proceeds[ The addition of atertiary base\ or preformation of the alcoholate anion\ is generally essential for the successfulpreparation of tertiary chloroformates^ they are also often thermally unstable\ undergoing quiteclean decomposition to the tertiary alkyl halide and carbon dioxide at or below room temperatureð70JOC0619Ł[ This occurs to a greater or lesser degree with retention of con_guration in the case ofoptically active alcohol substrates ð71JOC2410\ 75JOC0079Ł[ This complication can be avoided bysubstituting the corresponding tertiary ~uoroformate\ which is much more thermally stable "seeSection 5[03[2[0#[

Phenols do not generally react with phosgene at room temperature in the absence of an acidacceptor[ Good yields can\ however\ be achieved in chlorobenzene at 015>C with the addition of acatalytic quantity of stearyltrimethylammonium chloride[ The reaction will proceed slowly even atroom temperature ð54CI"L#680Ł[ In the presence of a base such as dimethylaniline\ reaction is oftenrapid and complete at 9>C ð56JOC299Ł[ Examples of the use of a two!phase system using concentratedaqueous sodium hydroxide as the base are well described in Houben!Weyl ð72HOU"E3#8Ł[

A few examples will now be discussed that illustrate a particular point\ or which may prove to beuseful extensions of the reaction of alcohols with phosgene[

Tertiary chloroformates bearing an electron!withdrawing group on the a carbon atom are ther!mally stable and apparently more resistant to hydrolysis than their unsubstituted analoguesð60JOU0832\ 67AG"E#250Ł[ Notwithstanding\ a satisfactory preparation of t!butyl chloroformate hasbeen reported[ By working at low temperature it proved possible to prepare t!butyl chloroformatefrom potassium t!butoxide and phosgene in a distilled yield of 50)[ This material showed noevidence of decomposition after 1 months of storage at −14>C ð70JOC0619Ł[ At the other extreme\primary and secondary alkyl chloroformates have been prepared from the corresponding alcoholsand phosgene in good yield in the vapour phase under continuous ~ow conditions\ using a reactiontime of 2Ð3 s at 099Ð149>C ð40JA2685Ł[ This method might form the basis of an industrial process[The problem of completely removing the tertiary base and its hydrochloride from chloroformateswhich cannot be distilled because of scale or instability may have been resolved by Dreiding andEgli\ who employed poly"3!vinylpyridine# as an acid acceptor to prepare chloroformate "6# inexcellent yield "Equation "1## ð75HCA0331Ł[ In this case\ the use of triethylamine caused partialdecomposition of the product[ During the preparation of a specialised amine!protecting group inthe "a!~uorenyl#methoxycarbonyl "Fmoc# family\ Ramage and Raphy found that the modi_ed~uorenylmethyl chloroformate could not be prepared by reaction of phosgene with the hydroxy!methyl~uorene in the presence of base because of spontaneous fragmentation to the corres!ponding alkene[ This was overcome by converting the alcohol into the O!trimethylsilyl ether\which with phosgene gave the chloroformate under neutral conditions "Scheme 00# ð81TL274Ł[Finally\ chloroformate preparation using phosgene generated in situ has been reported[ In a methodwhich may be of industrial signi_cance\ Japanese workers treated butanol with chlorine and carbonmonoxide in the presence of phosphine oxides at room temperature at 59 kg cm−1 pressure to givea 82) yield of butyl chloroformate ð68JAP6850010Ł[ On a laboratory scale\ should the preparationof a chloroformate using diphosgene "see Section 5[03[0[1[7# prove unsatisfactory\ addition ofactivated charcoal to the reaction will decompose the diphosgene completely to phosgene in solution[This method has been used to advantage in the preparation of carbamoyl chlorides\ and shouldalso be applicable to chloroformates ð74JOC604\ 89JMC1090Ł[

OOH

OH

OOH

OCOClCOCl2, poly(4-vinylpyridine), 0 °C

(7)

(2)


OH

Tbf

Tbf

OTbf Tbf

HO

Cl

NEt3

O-TMSTbf

OTbf

O

Cl

=

COCl2

TMS-Cl

–TMS-Cl

COCl2

Scheme 11

A series of chiral chloroformates has been prepared for the separation of optically active aminesby derivatization and reverse!phase liquid chromatography[ Formation from the respective alcoholswith phosgene in the presence of triethylamine proceeded in all cases without detectable racemizationð89JC482Ł[ Some representative structures\ "7#\ "8# and "09#\ are shown[ Finally\ the chloroformateof cyclic peroxide 2!hydroxymethyldioxetane "00# has been prepared with phosgene and pyridine inthe standard way[ In common with many less exotic chloroformates\ it is stable to ~ash chro!matography on silica ð75S229Ł[

OCOCl

CO2But OCOCl

OO

OCOCl

ONO2

OO

OCOCl

(8) (9) (10) (11)

"ii# From alcohols and diphos`ene or triphos`ene

The roles of diphosgene and triphosgene as alternatives to phosgene have already been explored"see Section 5[03[0[1[7#[ Konakahora et al[ have described the preparation of several sensitivechloroformates using these reagents\ and they discuss the e}ect of tertiary base nucleophilicity onthe yield obtained ð82S092Ł[ A potentially useful modi_cation of this method has been developed byJapanese workers\ who were able to prepare the chloroformate "01# in high yield using an in situtwo!step procedure[ Initial treatment of the alcohol with diphosgene and a tertiary base gave a largeamount of the corresponding carbonate[ This was avoided by _rst treating the alcohol with twoequivalents of diphosgene in the absence of base to give a 0 ] 0 mixture of chloroformate andcarbonate[ Addition of a catalytic amount of pyridine to this mixture converted the carbonate tochloroformate\ leading to its formation in an overall 67) yield "Scheme 01# ð80TL3260Ł[ The use ofdiphosgene and triphosgene in chloroformylation has been reviewed ð78MI 503!93\ 89MI 503!92Ł[

"iii# By chlorination of ROC"1X#Y compounds "X\ Y�S or O#

The chlorination of a variety of carbonates\ xanthates and thionoesters leads to chloroformatesð53CRV534Ł[ These methods are generally not of great synthetic importance because the startingmaterials are usually less available than the corresponding alcohol\ which is more commonly usedfor chloroformate synthesis[ In instances where attempts to form a chloroformate led only to thesymmetrical carbonate\ treatment of the latter with thionyl chloride or phosphorus pentachloridemay o}er a useful method of recovering the situation "Equation "2##[ Certain alcohols cannot readily

316One Halo`en

OH O O O

O

O O–Nu+

OO

Cl O Cl

ClCl

O Cl

O

3

Cl3COCOCl

OCl

O

Nu = pyridine 1 : 1

+

Nu

Cl–

+ COCl2 + Cl–

Cl

O

(12)

Scheme 12

Nu–

+ 3 Cl–

be converted to chloroformates with phosgene in the presence of base because of chemical instability[These include alcohols with a b electron!withdrawing group[ A high!yielding method of preparingchloroformates from alcohols of this type has been devised by Gilligan and Sta}ord\ who _rstconverted the alcohol to O!alkyl S!ethyl thiocarbonate with commercially available S!ethyl car!bonochloridothioate in the presence of iron"III# chloride[ This product is then treated with sulfurylchloride to provide the chloroformate in high yield "Scheme 02# ð68S599Ł[ Some of the alcoholsdescribed in this report contained b!nitro or b\b!dinitro functions^ compounds of this type presenta serious explosion hazard and should only be handled in laboratories equipped to deal with sucheventualities[ However\ this method is probably quite general^ it could also prove valuable inavoiding the symmetrical carbonate by!products which often reduce yields in chloroformatesynthesis[

O

RO OR

O

RO Cl(3)+ RCl + SO2

SOCl2

EtSCOClEWG

OHSO2Cl2EWG

O SEt

O

EWGO Cl

O

EWG = electron-withdrawing group

Scheme 13

Another use of this method is described by Folkmann and Lund in the preparation of acyl!oxymethyl chloroformates as precursors of pharmaceutical pro!drugs[ In this case\ chlorination ofthe intermediate thiocarbonate "02# is best achieved by sulfuryl chloride at room temperature in thepresence of BF2 =Et1O^ chlorine will also perform this cleavage "Equation "3## ð89S0048Ł[

SO2Cl2, BF3•OEt2, 0 °CO

R1 O O SR2

O O

R1 O O Cl

O

(13)

(4)

"iv# By electrophilic substitution of chloroformates containin` aromatic rin`s

A variety of aromatic electrophilic substitutions have been carried out on compounds in whichthe chloroformate group is already present[ In the search for new amine!protecting groups in the


Fmoc family\ Carpino brominated "8!~uorenyl#methyl chloroformate in the presence of iron"III#chloride to give the 1\6!dibromo analogue in 26) yield ð79JOC3149Ł[ Nitration of 3!methylphenylchloroformate is reported to give 3!methyl!2!nitrophenyl chloroformate "76)# ð79GEP1819275Ł[Phenyl chloroformate has been converted into its 3!sulfonic acid analogue by sulfur trioxide in asimilarly high yield ð80EUP304362Ł[

"v# Other methods

Hypochlorites bearing electron!withdrawing groups undergo carbon monoxide insertion intothe O0Cl bond at low temperatures to give chloroformates in excellent yield[ Thus\ a series ofper~uoroalkyl hypochlorites gave per~uoroalkyl chloroformates in quantitative yield ð58TL612Ł[Chlorine tri~uoromethanesulfonate "03# also undergoes a similar reaction to give the mixed anhy!dride "04# in 71) yield "Equation "4## ð71JFC"08#116Ł[

CO, –110–0 °C(5)ClOSO2CF3 ClCO2SO2CF3

(14) (15)

Electrophilic carbonylation of several substrates has been performed by treating an equimolarmixture of bromine and antimony pentachloride with carbon monoxide in liquid sulfur dioxide toyield the chloro!oxocarbonium ion "05#\ which can be captured by ethanol to give ethyl chloro!formate "Scheme 03# ð62TL1176Ł[

(16)

Br2 + SbCl5 + CO [BrCO]+ [SbCl5Br]– [ClCO]+ [SbCl4Br2]–liquid SO2 ROH

ROCOCl + H+ [SbCl4Br2]–

Scheme 14

Two methods of preparing methyl chloroformate from palladium bis"methoxycarbonyl# com!plexes have been reported ð82JOM"340#132Ł[ Since in these complexes the methoxycarbonyl ligand isobtained by treatment of a simple palladium complex with carbon monoxide in methanol\ and thechlorine atom for the decomposition step is supplied by copper"II# chloride or chlorine\ it is possiblethat this could form the basis of a catalytic preparation[

"vi# Preparation of halo`enated chloroformates

"a# a!Haloalkyl chloroformates[ Two important compounds in this class are commercially avail!able] trichloromethyl chloroformate\ which has been already discussed as a phosgene alternative"see Section 5[03[0[1[7#\ and a!chloroethyl chloroformate\ which has found use in the N!dealkylationof tertiary amines ð73JOC1970Ł[ The preparation of mono!a!chloroalkyl chloroformates can becarried out most conveniently by the reaction of phosgene ð73JOC1970Ł\ or a phosgene equivalentð78TL1922Ł\ with an aldehyde at or below room temperature "Scheme 04#[ Formaldehydeð72GEP2130457Ł and benzaldehyde ð72HOU"E3#8Ł also undergo this reaction\ but it has not beenreported for ketones[ Alternatively\ chloroformates bearing a hydrogen atoms can be readily chlori!nated photochemically[ Whilst this is an excellent method of preparing trichloromethyl chloro!formate ð68OS"48#084Ł\ and presumably other fully a!chloro!substituted chloroformates\ attemptsto prepare partially a!chlorinated compounds result in the formation of mixtures[ Thus\ partialchlorination of methyl chloroformate yields both chloromethyl chloroformate and dichloromethylchloroformate\ which can be isolated in moderate yield by fractional distillation[ These compoundscan be freed from associated trichloromethyl chloroformate by treatment with charcoal\ when onlythe latter decomposes to phosgene ð89S0048Ł[ An alternative radical chlorination employing sulfurylchloride can also be used to prepare a!chloroethyl chloroformate in 40) yield ð80JAN0972Ł[

RCHO + COCl2

SO2Cl2RCH2OCOCl O Cl

O

Scheme 15

R

Cl

R = H, alkyl, Ph

318One Halo`en

"b# b!Chloroalkyl chloroformates[ The preparation of b!chloroalkyl chloroformates is welldescribed ð72HOU"E3#8Ł[ The most general method involves pyridine!catalysed addition of phosgeneto an oxirane\ _rst described by Malinovsky and Modyantseva ð42JGU118Ł[ The reaction usuallyproceeds regiospeci_cally with unsymmetrical oxiranes to give the product with the chlorine on theless substituted carbon atom "Equation "5## ð42JGU118\ 46JCS1624Ł[ Several b!chloroalkyl chloro!formates have also been prepared by addition of chlorine to chloroformates bearing allyl orpropargyl groups ð48JAP483153Ł[ Treatment of ethylene carbonate with phosphorus"V# chloride alsogives b!chloroethyl chloroformate in high yield ð50CB433Ł[

COCl2, pyridineO

R3R1

R2

O

O ClCl

R3

R2R1

(6)

"vii# Preparation of enol chloroformates\ R0R1C1CR2OCOCl

The simplest member of this class\ vinyl chloroformate\ was the _rst to be prepared\ by pyrolysisof ethylene glycol bis"chloroformate#[ This has been well described by Lee\ who was able toachieve a moderate yield using a ~ow process ð54JA2832Ł[ An earlier report describing 1!propenylchloroformate ð23JA1996Ł has been reinvestigated by Olofson et al[\ who could not reproduce thework ð67JOC641Ł[ This group has subsequently carried out the majority of work in this area[ The_rst general synthesis emerged after failure to trap enolates prepared by many methods withphosgene[ The reaction of ethyl 1!propenyl ether with mercury"II# oxide gave di"ace!tonyl#mercury"II# in quantitative yield[ Reaction with phosgene at 9Ð14>C led to 1!propenyl chloro!formate in 75) distilled yield "Scheme 05# ð67JOC641Ł[ Another method of some generality hassince been developed[ Initially\ Olofson and co!workers developed a simple and convenient synthesisof 1\1!dichlorovinyl chloroformate by zinc dehalogenation of the adduct between phosgene andtrichloroacetaldehyde "Scheme 06# ð89JOC1139Ł[ Subsequently they have increased the scope of thismethod to the preparation of other enol chloroformates ð89JOC4871Ł[

COCl2OEt

O

O

Cl(MeCOCH2)2Hg

HgO, Hg(OAc)2

Scheme 16

COCl2 O

O

ClCl3CCHO

Cl

Cl3C O

O

Cl

Zn

Cl

Cl

Scheme 17

The corresponding imidate chloroformates "06#\ derived from secondary amides and phosgene\have also been reported "Equation "6## ð72HOU"E3#8Ł[

(17)

COCl2

ButN

O

O

ClButNHCOMe

•HCl(7)

"viii# Preparation of oxime chloroformates\ R0R1C1NOCOCl

Chloroformates derived from oximes and their tautomeric C!nitroso compounds have beenused as intermediates in the preparation of oxime carbonates\ which have been suggested ast!butoxycarbonylating agents ð66BCJ607Ł and as precursors to photolabile amine!protecting groupsð78TL0890Ł[ The oxime chloroformates were prepared in the standard way from the oxime and


phosgene or trichloromethyl chloroformate with pyridine or N\N!dimethylaniline\ in inert solvents"Equation "7##[

(8)NOH

R2

R1

NOCOCl

R2

R1COCl2

Conversion of the nitroso compound "07# to a mixture of "E#! and "Z#!oxime chloroformates "19#was accomplished by _rst treating "07# with TMS!Cl and zinc to give the silyl protected oxime "08#\followed by subsequent reaction with phosgene "Scheme 07# ð78IZV1738Ł[

COCl2NO-TMS

Cl

NOCOCl

Cl

Zn, TMS-ClN O

Cl

Cl(18) (19) (20)

Scheme 18

"ix# Formation of chloroformic acid anhydrides

Anhydrides of chloroformic acid with both carboxylic and sulfonic acids have been reported[They are prepared at low temperatures\ and are very reactive[ Amino acids protected as theirN!benzyloxycarbonyl derivatives form anhydrides on reaction with phosgene and triethylamine at−69>C ð46HCA593Ł[ These anhydrides react with alcohols at −69>C to form esters[ Reaction ofunprotected amino acids with phosgene or bis"trichloromethyl# carbonate "triphosgene# withoutbase at room temperature yields the cyclic amino acid carboxyanhydrides[ Since the amino groupof the amino acid is protonated to a great extent under these conditions\ it is possible that a similaranhydride formed by reaction of the carboxylate with phosgene is initially formed\ followed by ringclosure onto the amine function "Scheme 08# ð77TL4748Ł[

CbzNH CO2H

R1

CbzNH

R1

O

O

Cl

O

CbzNH CO2R2

R1

BnO2C CO2–

NH3+

Cl3COCOCl

50 °C BnO2CO

HN

O

O

COCl2, Et3N

–70 °C

R2OH

Scheme 19

The anhydride of chloroformic acid and tri~uoromethanesulfonic acid is formed by insertion ofcarbon monoxide into the O0Cl bond of chlorine tri~uoromethanesulfonate at low temperature"see Equation "4## ð71JFC"08#116Ł[

"x# Miscellaneous unusual chloroformates

The 06O NMR spectrum of the peroxy chloroformate "10# has been reported[ This compoundwas prepared from t!butyl hydroperoxide\ presumably by reaction with phosgene\ and is stable atroom temperature ð76TL5332Ł[

ButOOCOCl

(21)

Also reported is the reaction of phosgene with Hg"OSeF4#1 to give stable chlorocarbonyl penta!~uoroselenate\ ClCOOSeF4 ð70ZAAC"361#15Ł[ The corresponding ~uorocarbonyl derivative has beenknown for some time ð62IC658Ł\ but was prepared by the reaction of FOSeF4 with carbon monoxide[

320One Halo`en

5[03[2[0[2 Preparation of bromoformate esters\ ROCOBr

Bromoformates are poorly represented in the chemical literature[ Rosenmund and Do�ring pre!pared several alkyl bromoformates and benzyl bromoformate by the reaction of the appropriatealcohols with carbonic dibromide\ and reported that they tended to decompose within a fewdays ð17AP"155#166Ł[ A much more convenient method involves halogen exchange between thecorresponding chloroformate and anhydrous hydrogen bromide in methylene chloride\ catalysedby tetrabutylammonium bromide[ In this manner\ very high distilled yields of phenyl bromoformateand 1\1\1!trichloroethyl bromoformate were achieved ð77S396Ł[

5[03[2[0[3 Preparation of iodoformates\ ROCOI

Stable iodoformates have only been prepared in the last 19 years[ In general\ they require somesteric or electronic feature to render them su.ciently stable to allow their isolation[ Thus\ attemptsto form the iodoformate from cholesteryl chloroformate and sodium iodide led to 2!iodocholesterolin 49) yield\ presumably by decomposition of the unstable intermediate iodoformate ð56JOC1522Ł[Ho}mann and Iranshahi report that attempts to isolate iodoformates by halogen exchange wereunsuccessful with unhindered primary\ secondary or benzyl chloroformates ð73JOC0063Ł[ The _rststable iodoformate was prepared by irradiation of 8!triptycyl hydrogen oxalate "11# in the presenceof iodine and mercury"II# oxide[ The 8!triptycyl iodoformate "12# proved to be very stable to lossof carbon dioxide\ only decomposing to give 8!iodotriptycene "13# at 159>C "Scheme 19#[ This wouldbe expected for an ionic reaction occurring at the bridgehead carbon ð60JCS"C#2655Ł[ Subsequently\a range of carefully chosen iodoformates was prepared in high yield from the correspondingchloroformates by halogen exchange with sodium iodide in acetonitrile "Table 0#[ They could bestored at −19>C over copper powder[ Phenyl iodoformate was su.ciently stable to be distilled at57>C and 0 torr\ and underwent reaction with copper"I# cyanide to give the corresponding cyano!formate in good yield ð73JOC0063Ł[

(22)

= Trip TripO

OH

O

O

(23)

TripO I

O

(24)

Trip II2, HgO, hν

55%

260 °C

–CO2

Scheme 20

Table 0 Formation of iodoformates from chloroformates[

R Temperature(°C)

Yield(%)

CH2=CH 25 80

Ph 70 85

ButCH2 70 75

25 64

ROCOClNaI, MeCN

ROCOI

5[03[2[1 One Halogen and One Sulfur Function

Care should be exercised when searching or naming compounds of this class\ RSCOHal\ becauseconfusion can sometimes arise over the nature of the connectivity[ It is not always clear whether theacid component is connected to the alcohol or thiol by a C0S or C0O bond[ This ambiguity iscircumvented by the Chemical Abstracts nomenclature^ the title compounds are named as car!


bonohalidothioic acid S!esters[ Alternative names are formic acid halothio!S!esters or halo!thiolformate esters[ For convenience\ the last name will be used throughout this work[ However\many examples also exist where the sulfur atom is connected to atoms other than an alkyl or arylcarbon^ these can no longer be regarded as halothiolformates\ and are named appropriately as theyoccur\ for example chlorocarbonylsulfenyl chloride\ ClCOSCl[

5[03[2[1[0 Fluorothiolformate esters\ RSCOF

Several general methods of synthesis of ~uorothiolformate esters are described by Heywangð72HOU"E3#8Ł^ latterly\ publication in this area has been dominated by Haas and Della Ve�dovað80ZAAC"599#034Ł\ however their work has emphasized inorganic and spectroscopic aspects\ so it willnot be covered in depth here[

"i# Preparation from carbonic dihalides and thiols or thiophenols

Thiols and thiophenols react with carbonic chloride ~uoride and carbonic bromide ~uoride inthe presence of base to give ~uorothiolformate esters in good yields ð54JOC0206Ł[ It is also reportedthat tri~uoromethyl disul_de\ CF2SSH\ reacts with carbonic di~uoride in the presence of potassium~uoride at −14>C to give CF2SSCOF in 44) yield ð65JA5434Ł[ If the scope of this reaction can beextended to include thiols and thiophenols this could be a more convenient route\ since carbonicdi~uoride is commercially available[

"ii# Preparation from chlorothiolformates

The treatment of chlorothiolformate esters with hydrogen ~uoride at room temperature givesexcellent yields of ~uorothiolformate esters by halogen exchange ð54JOC0206Ł[

"iii# Preparation from ~uorocarbonylsulfenyl chloride and bromide\ FCOSHal

Fluorocarbonylsulfenyl halides react with a wide range of nucleophiles by displacement of thehalogen from the sulfenyl halide function ð56AG"E#694\ 58CB1607\ 69AG"E#355\ 62JFC"2#272\ 80SA"A#0508\80ZAAC"599#034Ł[ Some of these reactions are summarized in Scheme 10[ Fluorocarbonylsulfenylchloride is itself prepared by treating chlorocarbonylsulfenyl chloride with antimony tri~uoride insulfolane at 89>C ð58CB1607Ł\ whilst ~uorocarbonylsulfenyl bromide is prepared from ~uoro!carbonylsulfenyl chloride by reaction with trimethylsilyl bromide ð80ZAAC"599#034Ł[ A comparison ofthe reactivities of chlorocarbonylsulfenyl chloride and ~uorocarbonylsulfenyl chloride with aminesshows that chlorocarbonylsulfenyl chloride initially reacts at the carbonyl group\ whilst ~uoro!carbonylsulfenyl chloride reacts at the sulfur atom ð62JFC"2#272Ł[

"iv# Rearran`ement of aryl ~uorothionoformates

As the key step in the preparation of thiophenols from phenols\ aryl ~uorothionoformatesare thermally rearranged to ~uorothiolformates at temperatures of 199Ð499>C "Equation "8##ð77USP3643961Ł[

O F

S

S F

O

∆, 200–500 °C(9)

"v# Reaction of FCOSCl with electron!rich aromatic systems

Fluorocarbonylsulfenyl chloride reacts with pyrrole in the presence of pyridine at −19>C togive 1!pyrrolyl ~uorothiolformate in 68) yield ð66CB56Ł^ however\ whilst chlorocarbonylsulfenyl

322One Halo`en

O

F SCl(or Br)

O

F SSR

O

F SNSO

S

NR1 R2

NH

O

F SNCO

O

F SCF3

O

F NCS O

F S

S

Cl F, hν

SS F

O

O

F SCF3

O

F SSCN

O

F SCN

O

O CF3

Cl

Cl S

FS

F3CS F

S

F

O

F

Cl S

F3CSS

AgOCN

AgSCN

H2S

(CF3)2HgAgCN

F

O

–CO2

RSH

F

Cl S

FS F

O

S

F F, hνO

F

HN

R1 R2 TMS-NSO

NH

O

Scheme 21

hν

AgCO2CF3

H2O

SF

O

S

O

FSF

O

–CO2

⟨91SA(A)1619⟩⟨91ZAAC145⟩⟨73JFC(3)383⟩

⟨91ZAAC145⟩

⟨73JFC(3)383⟩⟨70AG(E)466⟩

⟨70AG(E)466⟩

⟨70AG(E)466⟩

⟨70AG(E)466⟩⟨91ZAAC145⟩

⟨73JFC(3)383⟩

⟨69CB2718⟩⟨67AG(E)705⟩

⟨69CB2718⟩⟨67AG(E)705⟩

⟨73JFC(3)383⟩⟨70AG(E)466⟩

⟨69CB2718⟩⟨67AG(E)705⟩

chloride undergoes the analogous reaction with thiophene in the presence of tin"IV# chloride\ the~uorocarbonyl analogue is prepared by reaction of ~uorocarbonylsulfenyl chloride with thi!enylmagnesium bromide only in poor yield "Equation "09## ð65CB1364Ł[

X = S; R = MgBr

X R X S

ClSCOF(10)

F

O

X = NH; R = H

"vi# Preparation of b!~uoroalkyl ~uorothiolformatesCompounds of the structure "14# have been reported to undergo chlorineÐ~uorine exchange with

spontaneous rearrangement in the presence of hydrogen ~uoride at −09>C to give b!~uoroalkyl~uorothiolformates "Equation "00## ð77JFC"39#254Ł[ The reaction appears quite general\ but yieldsvary in the range 29Ð59)[

HF, –10 °CR

S Hal

O

FHal

RS F

O

FF

(11)Hal = Cl, F

(25)

"vii# Other methods

Penta~uorosulfur carbonyl ~uoride F4SCOF has been prepared in low yield "09Ð04)#\ by theirradiation of oxalyl ~uoride in the presence of disulfur deca~uoride\ F4SSF4\ or penta~uorosulfurhypo~uorite F4SOF[ It appears to be a water!sensitive\ stable gas "b[p[ −09>C\ approximately#^ thestructure is supported by extensive spectroscopic and analytical evidence ð57JA2843Ł[


5[03[2[1[1 Chlorothiolformate esters\ RSCOCl

The preparation of chlorothiolformates has been thoroughly reviewed by Heywang up to 0871ð72HOU"E3#8Ł[ This section will thus brie~y cover the principal methods\ supplemented by anyrelevant material[

"i# Preparation from thiols or thiophenols and phos`ene

The overwhelming majority of alkyl or aryl chlorothiolformates are prepared from the cor!responding thiol or thiophenol or its sodium salt\ and phosgene ð72HOU"E3#8Ł[ If the sodium salt isnot used\ active carbon\ or an organic base such as triethylamine ð77EJM"12#450Ł\ pyridineð66JOC2575Ł or dimethylaniline ð60BCJ1404Ł is often added\ but the reaction will usually proceed inthe absence of base ð73ZAAC"497#025Ł[ Many literature examples employ a considerable excess ofphosgene\ often many times the theoretical amount necessary[ There is no evidence to suggest thatthis practice leads to increased yields providing a base is present\ and it should be vigorouslydiscouraged on the grounds of safety[ The replacement of phosgene by trichloromethyl chloro!formate has also been successfully achieved ð74JHC0532Ł[ In this report\ sodium hydride was usedto prepare heterocyclic thiol sodium salts in situ[ This is usually more convenient than forming thesalt using aqueous sodium hydroxide followed by precipitation and drying ð62BCJ0158Ł[ It appearsthat chlorothiolformates may be more thermally stable than their chloroformate counterparts^t!butyl chlorothiolformate can be distilled at 32>C and stored for several weeks at 3>C withoutsigns of decomposition ð66JOC2575Ł[

"ii# Preparation from sulfenyl chlorides and carbon monoxide

Alkyl and aryl sulfenyl chlorides are converted to chlorothiolformate esters in high yield whentreated with carbon monoxide at pressures of 69Ð399 bars[ Electronegatively substituted sulfenylchlorides such as 1\3!dinitrobenzenesulfenyl chloride and trichloromethanesulfenyl chloride failedto react under these conditions ð57CC416Ł[

"iii# Preparation from thiiranes and phos`ene

Ring opening of thiiranes with phosgene under pyridine catalysis gives b!chloroalkyl chloro!thiolformate esters in a manner analogous to the corresponding reactions with oxiranes "Equation"01## ð72HOU"E3#8Ł^ however\ the regioselectivity may not be the same[

COCl2 +pyridine

S

RR

S Cl

Cl

O

(12)

"iv# Preparation by controlled hydrolysis of trichloromethanethiol derivatives

Trichloromethanesulfenyl chloride can be hydrolysed in good yield to chlorocarbonylsulfenylchloride\ ClCOSCl\ by treatment with sulfuric acid containing the calculated quantity of waterð53GEP0113619Ł[ This method has also been employed in the preparation of bis"chlorocarbonyl#disul_de from bis"trichloromethyl# disul_de ð62CL0204Ł^ however\ other workers have had di.cultyreproducing this result ð72JOC3649Ł[ A milder hydrolysis using dilute hydrochloric acid in re~uxing

324One Halo`en

acetone enabled the preparation of "16# from "15# in 69) yield ð75SUL82Ł[ Previous attempts toprepare this compound by addition of chlorocarbonylsulfenyl chloride to cyclohexene resulted inthe formation of "18# through the intermediacy of the thiirane "17# "Scheme 11# ð69AG"E#43Ł[

SCCl3

Cl

S

Cl

Cl

O

S

Cl

Cl

OS

ClSCOCl

(26) (27)

(28)(27)

S

Cl

+ ClSCOCl

S

H2O, acetone, HCl

Cl

–COCl2

O

(29)

Scheme 22

"v# Preparation from alkoxydichloromethanesulfenyl derivatives

The thermal ð70LA0133Ł or Lewis acid!catalysed ð53FRP0261860Ł elimination of alkyl chloridesfrom a range of alkoxydichloromethanesulfenyl compounds "29# provides a general route to certainclasses of chlorocarbonylsulfenyl derivatives[ This area has been extensively covered in a series ofpublications by Barany and co!workers[ This work is summarized in Scheme 12 ð72JOC3649\ 72TL4572\73JCS"P0#1504\ 73JOC0932\ 75JOC0755Ł[ This reaction has been used for the e.cient preparation ofð07OŁchlorocarbonylsulfenyl chloride ð73MI 503!91Ł[

O

Cl SCl

S

RO Cl

S

RO SMe

S

RO Cl

Cl SS

S Cl

O O

RO SS

S OR

ClCl ClCl

O

Cl SX

+

RO SX

ClCl

(X = SMe)

SO2Cl2

Cl2

(X = Cl)

(X = SCOCl)

SCl2(X = SCl)

∆–RCl

∆, –2RCl

(X = SCl)

ROCSCl

Scheme 23

(30)

"vi# Miscellaneous reactions leadin` to chlorocarbonylsulfenyl derivatives

Chlorocarbonylsulfenyl chloride reacts with silver"I# cyanide to give chlorocarbonyl thiocyanate\in 54) yield ð58CB1607Ł^ several other nucleophiles also react preferentially at sulfur to give theproducts shown in Scheme 13 ð69AG"E#43Ł[ In the case of tri~uoroacetamide\ further reaction to the


1!oxo!0\2\3!oxathiazole occurs ð76JFC"25#318Ł[ In the reaction of bis"bistri~uoromethyl!aminoxy#mercury"II# "20# with thiophosgene\ migration of the bis"tri~uoromethyl#amino groupsfrom oxygen to sulfur occurs\ leading to "21# in 50) yield "Scheme 14# ð73JFC"13#374Ł[ Reaction ofthiophosgene with bis"tri~uoromethyl# sul_ne "22# also proceeds through a rearrangement to give"24#\ possibly through the intermediacy of "23# "Scheme 15# ð74CB3442Ł[ In the reaction of the allenicalcohol "25# with thiophosgene\ the initially formed carbonochloridothionic acid O!ester undergoesa ð2\2Ł sigmatropic rearrangement to the vinylic chlorothiolformate "26# ð81AG"E#755Ł[ This is anexample of the rearrangement of an allylic ester "Scheme 16#\ and thus may be very general^ however\no examples appear in Houben!Weyl ð72HOU"E3#8Ł[

O

Cl SCl

O

F SCl

O

Cl SSR

O

Cl S

O

Cl SORf

O

Cl SOR

O

RO SCl

O

R2N SCl

O

Cl SNR2

SN

OR O

O

Cl SNHCORO

Cl SCN

O

SCN SSCN

O

Cl SNCONF3C

F3C Li

SbF3AgSCN

AgCN

AgOCN

RSHRfOLi

ROH

CF3

CF3

RCONH2

R2NH

N

Scheme 24

⟨70AG(E)54⟩

⟨70AG(E)54⟩

⟨70AG(E)54⟩

⟨87JFC(36)429⟩ ⟨87JFC(36)429⟩

⟨69CB2718⟩

⟨69CB2718⟩

⟨69CB2718⟩

⟨69CB2718⟩⟨87JFC(36)429⟩

Scheme 25

CSCl2, –78 °C

(32)(31)

((CF3)2NO)2Hg

S

O Cl(CF3)2N

O

S Cl(CF3)2N

CSCl2

(34)(33)

S O

F3C

F3C

OS

S

F3C

F3CCl

Cl

Cl–

S

SClF3C

F3CCl

O

Cl

SClF3C

F3C

S

SF3C

F3C

–COS

–COCl2

(35)Scheme 26

∆

5[03[2[1[2 Bromothiolformate esters\ RSCOBr

Bromothiolformate esters have rarely been reported[ Haas and Lieb have prepared tri~uoromethylbromothiolformate by halogen exchange from tri~uoromethyl ~uorothiolformate and boron tri!bromide ð67CB1780Ł^ Haas et al[ also used the same method to prepare bis"bromocarbonyl# disul_de

326One Halo`en

•OH

•S

O

Cl S

O

Cl

∆

S

O

Cl

NaH, CSCl2

S

O

Cl

∆

(36) (37)

Scheme 27

from bis"~uorocarbonyl# disul_de ð62JFC"2#272Ł[ A poorly characterized example of carbon mon!oxide insertion into methanesulfenyl bromide to give methyl bromothiolformate is also reportedð72HOU"E3#8Ł[ This method is analogous to the reaction of sulfenyl chlorides with carbon monoxideand should proceed under milder conditions in view of the lower S0Br bond strength[

5[03[2[1[3 Iodothiolformate esters\ RSCOI

This class of compound does not appear to have been reported[

5[03[2[2 One Halogen and One Nitrogen Function

Compounds of the structure HalCONR0R1 are referred to in Chemical Abstracts as substitutedcarbamic halides[ Alternative names are halogenoformic amides\ carbamyl halides and carbamoylhalides[ The last name will be adopted in this work\ in line with common usage[ Other classes ofcompound incorporating the HalCON functionality also exist\ notably those where the nitrogenatom is part of a pseudohalide "e[g[\ isocyanate# or is part of an imide group[ These compoundsare variously named\ often as halogenocarbonyl derivatives[ The entire scope of this section iscomprehensively reviewed in Houben!Weyl up to 0871] carbamoyl halides by Heywangð72HOU"E3#25Ł^ bis"halogenocarbonyl# amines\ HalCONRCOHal\ by Hagemann ð72HOU"E3#0908Ł^halogenocarbonylcarbamic acid esters and amides\ HalCONRCOX "X�O\ N\ S# by Kraatzð72HOU"E3#0912Ł and Baasner ð72HOU"E3#0967Ł^ halogenocarbonylisocyanide dihalides and deriva!tives\ HalCON1CHal1\ by Hagemann ð72HOU"E3#0069Ł^ HalCON1CHalX "X�O\ N\ S# by Salz!burg ð72HOU"E3#0066Ł^ HalCONRCHal2 and derivatives by Marhold ð72HOU"E3#0192Ł^halogenocarbonyl isocyanates\ HalCONCO\ by Hagemann ð72HOU"E3#0123Ł^ and halogenocarbonylureas\ HalCONRCONRX "X�O\ N\ S#\ by Lieb ð72HOU"E3#0164Ł and Botta ð72HOU"E3#0202Ł[ Thepresent authors do not hope or wish to incorporate this vast\ well!researched body of knowledgeinto this review[ Their aim is to introduce readers to the main synthetic methods employed in thisarea\ incorporating some more recent references\ where they exist[

5[03[2[2[0 Carbamoyl ~uorides\ R0R1NCOF\ and other N!~uorocarbonyl compounds

The most important members of this class are carbamoyl ~uorides bearing one further substituenton the nitrogen atom\ RNHCOF[ Because of their thermal and chemical stability relative to thecorresponding carbamoyl chlorides\ they are used as intermediates in the synthesis of importantfungicides and insecticides where nitrogen substitution can be carried out\ even in the presence oftertiary bases\ without elimination to the isocyanate[ These N\N!disubstituted carbamoyl ~uoridescan then be further reacted with amines or alcohols to give\ respectively\ ureas and carbamates[

"i# Preparation from carbonic ~uoride halides

Although preparation from carbonic ~uoride halides is analogous to the very versatile reactionof phosgene with amines under base!catalysed conditions to form carbamoyl chlorides\ it is not areliable or accessible general method for the preparation of carbamoyl ~uorides[

Carbonic chloride ~uoride reacts predictably with diphenylamine to produce diphenylcarbamoyl


~uoride in good yield ð79EUP41731Ł^ however\ carbonic chloride ~uoride is not commercially avail!able\ so this method is not very attractive[ On the other hand\ carbonic di~uoride is commerciallyavailable^ however\ its reaction with amines does not usually result in the formation of carbamoyl~uorides^ reaction with piperidine or dimethylamine at room temperature leads to oxidative ~uo!rination to form the N!~uoro derivative in reasonable yield\ with the formation of carbon monoxideð73CC305Ł[ The same authors did isolate the carbamoyl ~uoride "28# in 69) yield from the reactionof "27# with carbonic di~uoride "Equation "02##[ However\ some classes of nitrogen compound are~uorocarbonylated by carbonic di~uoride[ Secondary amides give moderate yields of N!~uoro!carbonyl derivatives^ however\ it is di.cult to prevent concomitant conversion of the amide carbonylfunction to a èm!di~uoride ð51JA3164Ł[ The N!methoxycarbonyl!N!trimethylsilylhydrazine "39# isconverted to the N!~uorocarbonyl derivative "30# at −19>C in quantitative yield "Equation "03##ð71ZN"B#70Ł[ This may indicate that compounds with less basic nitrogen atoms are more likely tolead to N!~uorocarbonyl products[ Benzophenone imine is also reported to react with carbonicdi~uoride to give N!~uorocarbonylation in 39) yield ð57ZOR619Ł\ whilst at elevated temperaturesN!aryldi~uoroazomethines "31# add the elements of carbonic di~uoride under ~uoride catalysis togive N!~uorocarbonyl!N!tri~uoromethylanilines "32# in good yield "Scheme 17# ð54JOC3227Ł[ In asimilar reaction\ carbonic di~uoride adds to the imino~uoride from HF and HCN to giveCF1HNHCOF in 69) yield ð51JA3164Ł[ Phenyl isocyanate also adds carbonic di~uoride undercaesium ~uoride catalysis to give N\N!bis"~uorocarbonyl#aniline in 84) yield ð51JA3164Ł[ Finally\in a complex reaction\ carbonic di~uoride reacts with cyanogen ~uoride to give bis"tri!~uoromethyl#carbamoyl chloride\ "CF2#1NCOF\ in low yield ð70JFC"07#148Ł[ This compound canalso be prepared in high yield by the ~uorination of dimethylcarbamoyl chloride[

P

N

O O P

N

O O

COF

F

COF2, 25 °C

(38) (39)

(13)

COF2, –20 °C

(40) (41)

(14)NMe2N

CO2Me

TMS

NMe2N

CO2Me

COF

COF2

(42) (43)

PhNCS PhN

F

F

O

N FPh

CF3

Scheme 28

HgF2

"ii# Preparation from carbamoyl halides by haloènÐ~uorine exchanè

N!Carbonyl chlorides of many types of are readily prepared^ thus\ they make ideal startingmaterials for the preparation of the corresponding N!carbonyl ~uorides[ Several methods have beenreported[ The use of potassium ~uoride in sulfolane requires high temperatures\ and is thus limitedin its application^ any aliphatic chlorine atoms present are also likely to be exchanged ð67GEP1695572Ł[The use of the phase transfer catalyst 07!crown!5 enables the exchange to take place in high yieldat room temperature\ either in the presence or the absence of solvent ð68JOC0905Ł[ A more recentreport from Japanese workers suggests that a carefully dried mixture of potassium and calcium~uorides can e}ect quantitative exchange at 49>C in acetonitrile ð75CC682Ł[ Although reportedexamples are restricted to the preparation of N\N!disubstituted carbamoyl ~uorides\ the last twomethods may be applicable to N!monosubstituted derivatives\ unless the basic nature of potassium~uoride precludes this[

Predictably\ carbamoyl bromides are also reported to undergo exchange ð67GEP1695572Ł^ however\this is of little synthetic use\ due to their relative inaccessibility[

328One Halo`en

"iii# Preparation from alkyl or aryl isocyanates and hydro`en ~uoride or other ~uoride sources

The method of choice for the preparation of carbamoyl ~uorides bearing one further substituenton nitrogen involves addition of hydrogen ~uoride to an isocyanate[ Alkyl and aryl isocyanatesreact with hydrogen ~uoride in ether at room temperature to give quantitative yields of the cor!responding N!monosubstituted carbamoyl ~uorides ð34JCS753Ł[ By conducting the reaction at−79>C\ hydrogen ~uoride will also add to cyanic acid\ HOCN\ to give the unsubstituted carbamoyl~uoride\ H1NCOF\ which is a stable solid\ m[p[ 36>C ð39CB066Ł[ A more convenient\ but loweryielding\ method uses the commercially available\ stable pyridinium poly"hydrogen ~uoride# as botha solvent and hydrogen ~uoride source\ providing both alkyl and aryl carbamoyl ~uorides in39Ð59) yield ð68JOC2761Ł[

"iv# Preparation from other carbamoyl ~uorides

The thermal and base stability of monosubstituted carbamoyl ~uorides\ RNHCOF\ relative totheir carbamoyl chloride counterparts renders them excellent intermediates for the preparation offurther carbamoyl ~uorides by reaction at the nitrogen atom with a range of electrophilic reagents[The reaction with a wide variety of sulfenyl chlorides in the presence of a tertiary base has beenthoroughly investigated because the products can be transformed into a range of fungicidal andinsecticidal carbamates by reaction with hydroxyl compounds or amines "Scheme 18#[

O

N FAr

SCX3

O

N FMe

SNBun2

O

N NH

PhNH2

SCl2, pyridine

R = Me

Ar

SCX3

Bun2NSCl

R12NH

Ph X = halogen

R2OHO

NH

FR

O

N FMe

SCl

O

N OR2Me

SNR12

Scheme 29

R = Me

O

N FMe

SNR12

ClSCX3, Et3NR = Ar

pyridine⟨78JOC3953⟩

⟨82USP4333883⟩ ⟨84USP4473580⟩

⟨82EUP46557⟩⟨82JFC(19)553⟩

Other transformations which have been successfully carried out on particular carbamoyl ~uoridesare aromatic nitration and catalytic hydrogenation of aromatic nitro groups\ both in good yieldð79EUP41731Ł\ acylation with phosgene ð63GEP1200551Ł\ sulfoxide formation using m!chloro!perbenzoic acid ð70USP3144242Ł\ and stannylation with allyltin"II# halides ð66USP3947438Ł[

"v# Carbamoyl ~uorides arisin` from ~uorination

Carbamoyl ~uorides are often formed when appropriate substrates\ notably isocyanates\ are~uorinated[ However\ in common with many other ~uorinations of organic compounds\ the struc!ture of the products can rarely be predicted[ Fluorination of n!propyl isocyanate with ~uorine inFreon 00 can give n!propyl!N!~uorocarbamoyl ~uoride in up to 39) yield[ Further studies showthat the product does not arise from addition of ~uorine to the C1N of the isocyanate "Scheme29# ð56JOC0522Ł[ In two related reactions\ the ~uorination of tri~uoromethyl isocyanate ð68CB1047Łand tri~uoroacetyl isocyanate ð75JFC"23#140Ł with xenon di~uoride led to good yields of the ~uoro!carbonylhydrazines "34# and "35#\ respectively[ Their formation can be explained as arising from


elimination of xenon from intermediates of structure "33# "Scheme 20#[ Tri~uoromethyl isocyanatereacts with several other ~uoride sources to give a range of products "Scheme 21#[

HF F2Prn N • O

O

NH

FPrn

O

NF

FPrn

Scheme 30

Xe N

R

O

F

2

XeF2

R = CF3

XeF2

– CF4R = COF

R = COF

R = CF3

– Xe

– Xe

F3C NCO N N

FCO

CF3F3C

COF

N N

FCO

COFFCO

COF

F3C CONCO

Scheme 31

(44)

(45)

(46)

HF

N

CF3

COF

BrCsF

F3C N • O F3C N

Cl

COF

F3C N

COCl

COF

ClF CO, hν

O

NH

FF3C

Scheme 32

⟨73IC2890⟩

⟨57ZOB2243⟩

⟨76IZV209⟩

⟨74JA1770⟩

Electrochemical ~uorination of dimethylcarbamoyl chloride\ Me1NCOCl\ gives almost exclusivelythe per~uorinated product\ "CF2#1NCOF ð47JOC0465Ł[ When _ve! or six!membered cyclic ureas "36#are ~uorinated in water\ v!di~uoroaminoalkylcarbamoyl ~uorides "37# are formed in poor yield"Equation "04## ð69JA1985Ł[ Finally\ a range of "~uorocarbonyl#imidosulfur compoundsR0R1S1NCOF have been prepared^ ~uorination of CF2SNCO at low temperature leads to theformal 0\2!addition of ~uorine\ to give CF2FS1NCOF in good yield ð72CB0146Ł[ Compounds ofthe same class are formed in almost quantitative yield by the reaction of sulfur tetra~uoride ð75IS09Łor substituted analogues ð80CB1300Ł with silyl isocyanates "Scheme 22#[

O

NH

HN

F2NHN F

O

(15)F2, H2O

n = 2, 3

(47)

( )n( )n

(48)

"vi# Carbamoyl ~uorides from tri~uoromethylamines\ R0R1NCF2

N\N!Disubstituted formamides can be ~uorinated by silicon tetra~uoride in the presence ofpotassium ~uoride to give tri~uoromethylamines\ R0R1NCF2[ Where R0 and R1 are alkyl groups\addition of these compounds to crushed ice results in the carbamoyl ~uorides R0R1NCOF in over69) yield ð72JFC"12#196Ł[ Per~uoroalkyl tertiary amines bearing at least one CF2 group\ Rf

0Rf1NCF2\

are converted to the carbamoyl ~uorides Rf0Rf

1NCOF in 27Ð51) yield by 29) oleum\ preferablywith catalysis by MoCl4[ Where more than one NCF2 group is present\ only one is converted to givethe mono~uorocarbonyl derivative ð78JFC"34#182Ł[

330One Halo`en

SF4Si(NCO)4

Me2N

S

R

F

F

S NCOF

Me2N

R

S NCOF

F

F

TMS-NCOR = F, CF3

Scheme 33

"vii# Miscellaneous reactions yieldin` carbamoyl ~uorides

A variety of N!unsubstituted aziridines have been shown to react with tri~uoromethyl hypo!~uorite\ CF2OF\ at −39>C to give 49Ð099) yields of aziridine!N!carbonyl ~uorides "38#[ Thesecan rearrange on storing at room temperature to give high yields of b!~uoroalkyl isocyanates "49#in high yields "Scheme 23# ð79JFC"04#26Ł[

CF3OFNH

R2

R1

R3

R4

N

R2

R1

R3

R4

O

FF–

RT, several days

(at least two R groups = H)

R1

R4

R3

N

R2

F • O

Scheme 34

(49) (50)

R1, R2, R3, R4 = H, Me, Ph

The per~uorinated oxaziridine "40# reacts with a wide range of nucleophiles\ in the presence ofsodium ~uoride\ generally giving ~uorocarbonyl derivatives "41# in varying yields by attack at thenitrogen atom[ Reactions with diethylamine and potassium thiocyanate did not follow this course\and sodium azide and sodium cyanate failed to react "Scheme 24# ð68JFC"03#178Ł[ N!Monosubstitutedcarbamoyl ~uorides have been prepared by the reaction of an alcohol or an alkene with cyanogenchloride and HF "Equation "05## ð62GEP1231759Ł[ Finally\ a report claiming the formation ofF1NCOF in high yield by isomerisation of tri~uoronitrosomethane\ CF2NO ð25CB573Ł\ has beenreinvestigated and found to be incorrect^ the product appears to be a mixture of tri!~uoronitromethane and hexa~uoroazoxymethane "42# ð43JCS808Ł[

NuH = MeOH (80%), PriOH (88%), ButOH (93%), MeCO2H (32%), EtSH (30%); and KCN (40%)

Scheme 35

+

N

O

+ F–

F3CF

F

(51) (52)NuH

N

NuH

F3CF

O

N

Nu

F3CF

O

+ HF

(CH2)n (CH2)n

OH

(CH2)n

HN F

Oor

ClCN, HFn = 3, 4 (16)

N NCF3

O

F3C

–

+

(53)

"viii# Preparation of ~uorocarbonyl isocyanate

Whilst the chemistry of chlorocarbonyl isocyanate has been extensively explored\ and has beenthe subject of several reviews "see Section 5[03[2[2[1#\ the reactions of ~uorocarbonyl isocyanate do


not appear to have been similarly examined^ this is probably because no convenient synthesis yetexists[ Until the early 0889s\ all the methods available involved the use of COF1\ often at hightemperatures[ However it has been shown that commercially available chlorocarbonyl isocyanatewill undergo halogen exchange in moderate yield with chlorine ~uoride or xenon di~uoride[ Themethods available are summarized in Scheme 25[ Several preparations of ~uorocarbonyl iso!thiocyanate\ FCONCS\ have also been described "Scheme 26#[ These are mainly analogous tothose described for ~uorocarbonyl isocyanate^ formation by halogen exchange has not yet beeninvestigated[

Scheme 36

TMS-NCO

O

NCO

NCO

KOCN

Si(NCO)4

COF2180 °C100%

COF2400 °C

COF2280 °C

70%

22%

KOCN

75%

ClF

51%

XeF2

36%COF2280 °C

KF

8%

F NCO

O

b.p. 26 °CCl NCO

O

⟨73CB1752⟩

⟨73CB1752⟩

⟨92ZAAC150⟩

⟨67CB1082⟩

⟨67CB1082⟩

⟨67AG(E)871⟩

Scheme 37

TMS-NCS

b.p. 63.5 °C

O

NCS

NCS

KSCN

COF250 °C

COF2140 °C

20%

17%

COF250 °C

100%

AgCN

20%

F NCS

O

F SCl

O

⟨73CB1752⟩

⟨67AG(E)871⟩

⟨67AG(E)871⟩

⟨67AG(E)705⟩

5[03[2[2[1 Carbamoyl chlorides\ R0R1NCOCl\ and other N!chlorocarbonyl compounds

Carbamoyl chlorides are quite often rather unreactive towards nucleophiles\ and can often bepuri_ed by chromatography and recrystallised from alcohols without decomposition[ Perhapsbecause of their relative lack of reactivity\ or\ in 0882\ the discovery of their carcinogenic potentialðB!82MI 503!90Ł\ their use in synthesis has been quite limited[ Carbamoyl chlorides bearing one furthersubstituent on the nitrogen atom are important intermediates in the preparation of isocyanates\ butare not usually isolated[ Carbamoyl chloride itself\ H1NCOCl\ is well described but of limitedstability^ it has found use in the amidation of aromatic systems under FriedelÐCrafts conditions ðB!53MI 503!90Ł[ Some classes of N!chlorocarbonyl compounds are very reactive^ when the nitrogen ispart of an aromatic ring system\ reaction with alcohols is often instantaneous[

This section encompasses a diversity of compound types[ The authors have ordered the contentsby reagent and:or reaction type\ rather than by the structure of the product formed[ The exceptionto this is the _nal subsection\ which is devoted to the synthesis of chlorocarbonyl pseudohalogenides[This area\ up to 0871\ is covered in great depth in Houben!Weyl\ volume E3^ this work includesmany tables of speci_c compounds and synthetic details[

332One Haloèn

"i# Methods involvin` the use of phosène

Most compounds with a nitrogen atom bearing a hydrogen or TMS function\ or which cantautomerize to yield a nitrogen atom bearing a hydrogen\ will react with phosgene to give variousN!chlorocarbonyl compounds[ This is by far the most commonly encountered method of preparingsuch compounds[ The use of phosgene can often be avoided by substituting one of the phosgenealternatives\ diphosgene or triphosgene^ these are treated separately in the next subsection[ Whatfollows is an attempt to make some general comments for various classes of nitrogen compounds\which are summarized in Scheme 27Ð31[ Compounds which react abnormally with phosgene arediscussed at the end of this subsection[

"a# Reaction of phosène with secondary amines\ R0R1NH\ to ìve R0R1NCOCl[ Since reactionsof nucleophiles with phosgene proceed with the elimination of hydrogen chloride\ it might beexpected that the reaction of phosgene with basic secondary amines should proceed to the stagewhere 49) of the amine is converted to product\ whilst the remainder is converted to the non!nucleophilic amine hydrochloride[ This is in fact the case at temperatures near to ambient and belowð74CB1183Ł^ however\ at re~ux in toluene with an excess of phosgene\ total conversion to thecarbamoyl chloride can occur in excellent yield ð77MI 503!90Ł[ The addition of a tertiary base as anHCl acceptor not only allows full utilisation of the secondary amine\ but also enables the quantityof phosgene to be reduced[ Stoichiometric amounts of phosgene can sometimes lead to yieldsapproaching 84) ð78JCS"P0#0616Ł^ however\ the use of 0[4Ð1[9 equivalents is more usual[ As thequantity of phosgene is reduced\ the possibility of symmetrical urea formation increases[ This israrely speci_cally mentioned as a problem in the literature^ however\ isolated yields of carbamoylchlorides are often only moderate[ An internal tertiary basic centre obviates the need for the additionof a further HCl acceptor in some cases ð76IJC"B#637Ł^ the success of this reaction depends on thetertiary centre hydrochloride of the starting material being to some extent soluble in the reactionmedium\ so the use of a more polar solvent may be bene_cial in this case[

In the reaction of secondary amines with phosgene\ anion formation using sodium hydride canalso lead to high yields of carbamoyl chlorides ð78MI 503!92Ł^ this method is potentially useful whenseparation of the product from the tertiary base hydrochloride could be problematical[ Alternatively\the use of an N!trimethylsilylamine as the amine component should allow smooth reaction withphosgene\ volatile trimethylsilyl chloride being the only by!product ð58ZOB1487Ł[ N\N!Disubstitutedcarbamoyl chlorides can be very stable^ examples exist of reactions in tri~uoroacetic acid and waterleaving the carbamoyl chloride unchanged ð89S0954Ł[

"b# Reaction of phosène with primary amines\ RNH1\ and ammonia\ to ìve RNHCOCl andH1NCOCl[ Phosgene reacts with primary amines to give N!monosubstituted carbamoyl chlorides\RNHCOCl[ On treatment with tertiary bases\ or thermally\ under re~ux in benzene or toluene\these carbamoyl chlorides eliminate hydrogen chloride to give isocyanates in high yield[ Because ofthe uncertainty involved in isolating the carbamoyl chlorides due to their instability\ the preferredsubstrate for further reactions is usually the isocyanate^ the reaction of nucleophiles with isocyanatesgives rise to the same product as the corresponding N!monosubstituted carbamoyl chloride\ andoften with the advantage that no acid acceptor is necessary "Scheme 27#[ Mono! or bisilyl!substitutedprimary amines react with phosgene at 9>C to give isocyanates directly\ with no isolable carbamoylchloride intermediates ð58ZOB1487Ł[

R1NH2

COCl2R1NHCOCl R1NCO

R1NHCO2R2

R2OH–HCl

R2OH

HCl

∆ or Et3N

Scheme 38

Primary amines react cleanly with phosgene in the gas phase at 164>C to give 69Ð89) yields ofN!monosubstituted carbamoyl chlorides^ ammonia undergoes the same reaction at 399Ð499>C togive carbamoyl chloride ð38AG072\ 49JA0777Ł[ Although secondary amines also undergo this reaction\it is most unlikely to be the best method of preparation of any particular N\N!disubstitutedcarbamoyl chloride[

"c# Reaction of phosène with tertiary amines[ The initial reaction of phosgene with tertiaryamines gives rise to acylammonium salts ð81JOC4025Ł[ These will often eliminate an alkyl chlorideon standing for 13Ð61 h at room temperature to give N\N!disubstituted carbamoyl chlorides[ Onhydrolysis\ the unstable N!carboxylic acids lose carbon dioxide to give secondary amines "Scheme


28# ð64LA1116\ 72JHC0366\ 74AF106\ 78AF428Ł[ This dealkylation can proceed in good yield\ and is auseful alternative to the Von Braun reaction\ which utilises cyanogen bromide to accomplish thesame transformation ð19CB590Ł[ Pyridine was thought to form a stable bispyridinium salt "43# withphosgene ð45CB1451Ł[ Reinvestigation has led to reassignment of the structure as "44# ð77JOC5034Ł[

N Me

R2

R1

N

R2

R1

COCl

MeCOCl2 –MeCl

Cl–

+N COCl

R2

R1H2O

NH

R2

R1

+ CO2 + HCl

Scheme 39

N N

O

2Cl–

+ +

(54)

N+

(55)

N

COCl

H

Cl–

"d# Reaction of phosène at heteroaromatic nitroèn atoms[ Aromatic heterocycles which carry ahydrogen atom on a cyclic nitrogen\ or which can tautomerize to do so\ react with phosgene to giveN!chlorocarbonyl derivatives^ amongst these are imidazole ð68LA0645Ł\ benzimidazole ð66S693Ł and4!aryl!0\2\3!oxadiazol!1"2H#!ones ð78JHC120Ł[ Indole reacts with phosgene to give the unexpectedproduct "45# ð73IJC"B#875Ł[ N!Trimethylsilyl heterocycles also react with phosgene to give similarproducts^ examples include imidazoles and pyrazoles ð79ZOB764Ł\ and 0\1\3!triazoloð3\2!aŁpyridin!2"1H#!one ð72BCJ1858Ł[ In the latter example\ the N!trimethylsilyl derivative "46# and the parentheterocycle "47# react with phosgene to form di}erent N!chlorocarbonyl compounds "Scheme 39#[

N NH

COCl(56)

NN-TMS

N

O

NN

N

O–

NNCOR

N

O

COCl

NNH

N

O(58)

COCl2 RCO2H

–CO2NNCOCl

N

O

NN

N

O–

(57)

+COCl2

COR

RCO2H

–CO2

+

Scheme 40

These heterocyclic N!chlorocarbonyl compounds are usually very reactive towards nucleophiles["e# Reaction of other N0H compounds with phosène[ Many other classes of N0H!containing

compounds also react with phosgene with the elimination of HCl to give N!chlorocarbonyl deriva!tives[ These include oximes\ hydrazines\ ureas\ guanidines\ carbazates and sulfamoyl chlorides[Imines\ amides and N!silyl amides also react\ but the initial products can sometimes rearrange[Compounds which have tautomeric forms containing N0H bonds can also react to give theN!chlorocarbonyl derivatives of that tautomer^ N!substituted iminoethers "48# follow this path\

334One Haloèn

unless the oxygen substituent is a silyl group "59#\ when they give the product expected from theiramide tautomer[ These reactions are summarized in Scheme 30[

NCO

Ar RCl

NHN

O

N

OMe

Ph

NMeCOCl

N

NR3COCl

R2N

R1N

R4

R3 R2

NR1COCl

N

N

COCl

O

O

R

O

NHR2

O

RHN NRCOCl

N

COCl

Ar NHCO2R

N NR3COCl

R2

R1

COCl

COCl

R1

N

COCl

R SO2Cl

N

OMe

NHHN

O

O

RHN NHR

Cl

NHR2R1 MeN

RCO TMS

N

N

OR

TMS-O

NR1

R3

R4

R2

NHR3

R2N

R1N

PhNHMe

N

N NHR3

R2

R1

N

Ar R

COCl

N

COCl

R1 OR2

HN

R1 OR2

HN

R SO2Cl

R = alkyl

COCl2

ArNHNHCO2R

(59)

NH

Ar R

RCONMeCOCl

R2 = HR2 = COMe

Scheme 41

(60)

⟨80S85⟩

⟨72S81⟩

⟨72S39⟩

⟨80S85⟩⟨68ZOR720⟩⟨69CB2972⟩

⟨91AP917⟩

⟨86TL113⟩

⟨89JMC228⟩

⟨89MI 614-04⟩⟨69ZOB220⟩⟨77ZOB1063⟩

⟨61GEP115721O⟩⟨86JOC3494⟩

⟨64JOC2401⟩

⟨85SC697⟩

⟨78GEP2828969⟩

⟨82MI 614-03⟩

⟨8OT3543⟩⟨78JCS(P1)1066⟩

"f# Reactions of compounds containin` C0N multiple bonds with phosène[ Many compoundswhich contain carbon multiply bonded to nitrogen initially add phosgene across the carbonÐnitrogenbond to give a!chloroalkyl N!chlorocarbonyl derivatives[ If these adducts possess the capacity toeliminate HCl\ this is likely to occur[ This behaviour is found in suitably substituted imines[ Whereelimination of HCl cannot occur\ the initial adducts are stable\ and can be useful bifunctionalintermediates in heterocyclic synthesis[ Certain imines\ carbodiimides\ nitriles and cyanamides fallinto this category[ These reactions are summarized in Scheme 31[

"`# Abnormal reactions of N0H compounds with phosène[ N\N!Diphenylformamidine "50# reactswith two molecules of phosgene\ exemplifying at the same time the two modes of reaction discussedin the two previous subsections[ Although the initial product "51# cannot eliminate HCl readily\ itis extremely sensitive to hydrolysis\ and it is the initial hydrolysis product "52# which eliminates HClto form N!chlorocarbonyl!N!phenylformamide "53# "Scheme 32# ð75JOC3372Ł[

The rearrangement of v!alkoxyalkyl! and v!phenoxyalkylcarbamoyl chlorides "54# to thev!chloroalkyl carbamates "55# proceeds even at room temperature when n�1 or 2[ More vigorousheating leads to the cyclic carbamates "56# ð64JCS"P0#0725Ł "Scheme 33#[

When 2!hydroxymethylpiperidine reacts with phosgene as its PTSA salt the expected chloro!formate "57# is formed[ If the chloroformate free base is liberated at −59>C with triethylamine\


COCl2

NCOCl

Cl

Ph

NCOCl

Cl

Cl

NCOCl

Cl

Me2N

Cl

RN NRCOCl

ArN

COCl

Cl

NRCOCl

Cl

Ar

Cl

NR5COCl

R4

R3

R1

R2

R3

R2 R4

NR5COCl

R4

NR5R3

R1

R2

CH2NAr

NMe2N

NAr

R

NCl

Scheme 42

N •R

NR

NPh

–HCl

R1 = H

⟨87JHC945⟩

⟨73CJC333⟩

⟨72S39⟩

⟨77GEP2708024⟩

⟨69BRP1169158⟩

⟨71BCJ2182⟩

⟨63JOC1427⟩⟨78JOC4530⟩⟨81JOC5226⟩

(62)(61)

H2O2 COCl2H

PhN

PhNH

PhN

PhN

COCl

COCl

Cl

PhN

PhN

COCl

OH

ClO

COCl

CHO

NPh

Scheme 43

+ PhNCO

(63) (64)

O

N

(CH2)n

O

R2Cl–Cl–

Cl

N

(CH2)n

O

R2

O

R1 R1

+

O

N

(CH2)n

O

R1

N

(CH2)n

Cl

Scheme 44

R1

CO2R2

(65)

(66)

(67)

+ R2Cl

RT

180 °C

migration of the chlorocarbonyl group from oxygen to nitrogen occurs\ to give the stable carbamoylchloride "58# in high yield[ The same reaction course was observed for 2!hydroxypiperidine[ Com!pounds "57# and "58# readily cyclise in the presence of triethylamine to give the bicyclic carbamate"69# "Scheme 34# ð79JOC4214Ł[

The N!chlorocarbonyl derivatives of the O!benzylhydroxylamine "60# and proline "62# cyclisereadily to give the corresponding anhydrides "61# ð81TL1518Ł and "63# ð80JOC640Ł "Scheme 35#[

"ii# Methods involvin` diphos`ene or triphos`ene

The role of trichloromethyl chloroformate "diphosgene# and bis"trichloromethyl# carbonate "tri!phosgene# as alternatives to the use of phosgene has already been discussed "see Section 5[03[0[1[7#[In the preparation of carbamoyl chlorides both reagents react to give the same product as wouldhave been anticipated if phosgene had been employed to carry out the transformation "Scheme 36#[

336One Halo`en

(70)

(68)

(69)

NH2

OH

+NH2

OCOCl

+

NCOCl

OH

N

O O

NCOCl

OCOCl

Scheme 45

NH

OH

COCl2, 0 °C

H+

COCl2

Et3N, –60 °C

Et3N, RT

COCl2, RT

Et3N, RT

–65 °C

(73) (74)

NH

CO2HCOCl2, Et3N N

OH

O

O Cl

N

O

O

O

(71) (72)

COCl2, 45 °C 70 °C

Scheme 46

CO2H

NHOCH2Ph NPhCH2O

OH

O

Cl

O

NO

O

O

PhCH2O

Cl3COCOCl (diphosgene)Et3N

(Cl3CO)2CO (triphosgene)pyridine

N

O

COCl

HN

O

Ph N

R

COCl

Ph N

R

NBn

R

COCl

NHBn

R

NR

COCl

NHR

ClN

COCl2

ClNH

N

COCl

Me

O

Ar N

COCl

Me

NHMe

Ar NMe

O-TMS

Scheme 47

2

⟨92S1216⟩

⟨92TL3483⟩

⟨92JMC3641⟩

⟨86MI 614-01⟩

⟨91TL259⟩

⟨89TL3229⟩⟨87AG(E)894⟩


"iii# The reaction of isocyanates with X0Cl to `ive RNXCOCl

Isocyanates add hydrogen chloride\ acyl chlorides\ sulfur dichloride\ other sulfenyl chlorides andphosgene across the C1N bond to give N!carbonyl chlorides[ Vinyl isocyanates add two moleculesof hydrogen chloride to give reactive bifunctional electrophiles "64# ð79AG"E#190Ł\ and carbonylisocyanates R0CONCO react with phosphorus"V# chloride to give "65# ð54TL1312\ 55CB128Ł\ theunsaturated analogues of "64#[ Reaction with boron trichloride leads to dimerisation and formationof N!chlorocarbonyl ureas "66# ð69AG"E#261Ł[ These reactions are summarized in Scheme 37[ Manyof these products are useful intermediates for the synthesis of heterocycles^ several examples areillustrated[

O

H2N Cl ON

O

R

O

Cl

Cl

NR

COCl

COCl

R2

R1 NHCOX

X

NCOCl

Cl

R1

N

S

Cl

NRCOCl

R1

NS

N

O

R1

O

RNR

COCl

COR1

NR

COCl

COCl

Scheme 48

N N

O

O

R R

NR

SCl

COCl

NR

H

COCl

NR

H

N

O

COCl

R

N • O

R

R = Hi.e. HOCNHCl

(COCl)2

R = CH=CR1R2

2HX (X = Cl, Br, I)

R = R1CO

NSCl

ClR1

R1COClR = alkylCOCl2

active carbon

BCl3

HCl

∆ ortertiary base

SCl2

pyridine

PCl5

(75)

(76)

(77)

⟨1899CB1116⟩⟨71GEP2128672⟩

⟨86JOC3781⟩

⟨70AG(E)372⟩

⟨71GEP1932830⟩⟨85EUP136147⟩⟨70GEP2008115⟩

⟨66AG(E)672⟩

⟨66CB239⟩⟨65TL2423⟩

⟨80AG(E)201⟩

⟨84JOC3675⟩

"iv# Methods involvin` reaction with carbon monoxide

The N!chloro derivatives of primary and secondary alkylamines can be carbonylated by carbonmonoxide at 59 atm in the presence of palladium metal or palladium"II# salts[ The products areN!monosubstituted carbamoyl chlorides "29Ð39)# and N\N!disubstituted carbamoyl chlorides "51Ð88)#\ respectively "Scheme 38# ð60JOC747\ 81MI 503!90Ł[ The iron tricarbonyl complex "67# adds theisobutyronitrile anion[ Oxidation of the reaction mixture with copper"II# chloride produced thecarbamoyl chloride "68# in 61) yield "Equation "06## ð77MI 503!91Ł[

R1

HN

R2 R1N

R2

Cl

R1N

R2

COClHOCl CO, Pd

R1 = R2 = alkyl, 62–69%

R1 = H, R2 = alkyl, 33–38%

Scheme 49

338One Halo`en

(17)

(79)(78)

N, CuCl2, –78 °C–

72%NPh Ph NCOClPh

Fe(CO)3Ph

N

"v# Preparation from formamides\ R0R1NCHO

Several methods of converting formamides into carbamoyl chlorides have been reported\ employ!ing various chlorinating mixtures\ and usually proceeding in 59Ð69) distilled yields[ These methodsare summarized in Table 1[

Table 1 Methods for the conversion of formamides into carbamoyl chlorides[

R1 R2 Conditions Yield(%)

Ref.

Me Me SO2Cl2, 180 °C 62AG861

Me Me SO2Cl2, pyridine, CH2Cl2, RT 62 68CB113

Me Me 69

–(CH2)4– 77

–(CH2)5– 59

–(CH2)2O(CH2)2– 66

Me n-C8H18 70

Me Ph 62

SCl2, pyridine, CH2Cl2

PCl3, SOCl2 71CB969

68CB113

R1R2NCHO R1R2NCOCl

"vi# Chlorination of carbamic acid esters\ thiolesters and related compounds

Carbamic acid esters can be cleaved by various chlorinating agents to yield N!chlorocarbonylcompounds[ This provides a method of converting primary or secondary amines to carbamoylchlorides in good yield without the use of phosgene or a phosgene equivalent "Table 2#[ In a variantof this reaction\ chlorine cleaves 2\4!dioxo!0\1\3!dithiazolidines to yield bis"chlorocarbonyl#amines"Equation "07## ð69S431Ł^ in a similar reaction\ the compound "79# produces chlorocarbonyl iso!cyanide dichloride "70# "Equation "08## ð60CB1621Ł[

Table 2 Cleavage of carbamic acid esters[

R1 Yield(%)

Ref.R2 X Reagent

R1R2NCOX R1R2NCOClR1R2NHreagent

1° or 2° alkyl 1° or 2° alkyl OEt POCl3 42–79 87SC1887

Me Me O-TMS PCl5 83 81MI 614-02

Ph Me O-TMS PCl5 80 91OM366

(NO2)2CFCH2 (NO2)2CFCH2 SEt SO2Cl2 85 82JCED97

(NO2)3CCH2 H SEt PhSCl (or Cl2) 84 85JOC5879


S

SNR

O

O

NR

COCl

COCl

Cl2

25–83%

R = alkyl, Bn, Ar

(18)

(19)S

SN

Cl

O

N

COClCl2

53% Cl

Cl

(80) (81)

"vii# Other methods of preparin` N!chlorocarbonyl compounds

Photochemical chlorination of N!methylocta~uoropyrrolidine leads to the trichloromethyl deriva!tive "71# in 84) yield\ which can be converted to the N!chlorocarbonyl compound "72# by treatmentwith oleum at room temperature in 73) yield ð72JFC"11#410Ł[ N!Trichloromethyl!2\5!dihydro!0\1!oxazines "73# can also be hydrolysed to the corresponding N!chlorocarbonyl compounds "74# in goodyield^ however\ only brief treatment with water was necessary to accomplish this transformationð78CJC1042Ł[

N

N

O

RX

X

F

F

FF F

F

F

F

(82) X = CCl3(83) X = COCl

(84) X = CCl3(85) X = COCl

Certain strained heterocycles are cleaved by hydrogen chloride to give N!chlorocarbonyl products^thus 0\2!diazetidine!1\3!dione "75# provides the urea derivative "76# in 80) yield "Equation "19##ð55CB2092Ł\ whilst diaziridinones "77# lead to hydrazine derivatives "78# in good yield "Equation"10## ð58JOC1143Ł[

NHHN

O

O

H2NCONHCOClHCl

(86) (87)

(20)

N N

O

R R

(88) (89)

HClRNHNRCOCl (21)

Chlorocarbonyl isocyanate can undergo cycloadditions to multiple bonds to produce N!chloro!carbonyl derivatives^ in this way\ the enamine "89# gave the N!chlorocarbonylazetidine "80# in 75)yield "Equation "11## ð66ZOR189Ł\ and nitrile oxides "81# gave 0\1\3!oxadiazol!4!ones "82#\ also inhigh yields "Equation "12## ð77S883Ł[ Pyrrole forms a stable N!carboxylic acid\ which reacts normallywith oxalyl chloride or the Ghosez reagent to form unstable N!chlorocarbonylpyrrole ð73CC529\76JOC1208Ł[

340One Halo`en

–20 °C(22)N

(CH2)n (CH2)nN

O

COCl

N

O

O

n = 3, 85%n = 4, 86%

(91)

ClCON • O

(90)

+

(93)(92)

ClCON • O (23)+ N OArON

NAr O

COCl

+ –

"viii# Preparation of chlorocarbonyl isocyanate and isothiocyanate

Chlorocarbonyl isocyanate is a thermally stable\ very reactive bifunctional molecule\ and isof considerable importance\ particularly in the preparation of heterocyclic compounds[ It is acommercially available colourless liquid\ b[p[ 53>C\ which can be stored inde_nitely in the absenceof moisture[

It was _rst prepared in 0858 by Gottardi and Henn in poor yield by the photolysis of chlorineisocyanate ð58M0759Ł[ Several other methods have been reported\ involving high!temperature reac!tions of phosgene with isocyanates or cyanates ð62CB0641Ł^ however\ only one method\ due toHagemann\ has emerged as both high yielding and economical[ In this synthesis\ inexpensivemethyl isocyanate or cyanogen chloride is converted in high yield to N!chlorocarbonyl isocyanidedichloride\ which is partially hydrolysed with methanesulfonic acid under carefully controlledconditions to give N!chlorocarbonyl isocyanate in over 89) yield "Scheme 49# ð62AG"E#888Ł[ Thechemistry of chlorocarbonyl isocyanate has been extensively reviewed ð66AG"E#632\ 89H"20#0266\82T2116Ł[

COCl2

ClCN

Scheme 50

N • ON • O

Cl

• O)2

COCl2, 400 °C

2%

Cl

O2SO

NO Cl

Me

COCl2

89%

KOCN

90%

250 °C54%

180 °C56%

Cl2, hν

15%

(NO C • O)4Si(N

COCl2active carbon150 °C

N

Cl

Cl

N • O

Me

Cl

O

Cl2, hν

Cl

O

90%

MeSO3H

⟨73CB1752⟩ ⟨ 73CB1752⟩

⟨73CB1752⟩⟨69M1860⟩

⟨73AG(E)999⟩


The sulfur analogue\ N!chlorocarbonyl isothiocyanate\ may have been prepared as early as 0859by the reaction of phosgene with lead"II# thiocyanate ð59AP"182#049Ł^ however\ full characterisationwas not carried out[ Ja�ckh and Sundermeyer failed to prepare this compound from phosgene andpotassium thiocyanate\ probably due to its instability at the high temperatures employed ð62CB0641Ł[A further preparation from chlorocarbonyl isocyanide dichloride and phosphorus"V# sul_deð58AG"E#19Ł has been disputed by Bunnenberg and Jochims\ who failed to repeat this work^ however\these workers _nally successfully prepared N!chlorocarbonyl isothiocyanate in high yield by thermalelimination of carbon monoxide from oxalyl chloride isothiocyanate at 74>C in the presence ofactive carbon "Scheme 40# ð70CB0635Ł[

N • S

ClCO

N • S

ClCOCO(COCl)2

NH4SCN, liquid SO2

93%

85 °C

–CO87%

Scheme 51

5[03[2[2[2 Carbamoyl bromides\ R0R1NCOBr\ and other N!bromocarbonyl compounds

Although carbamoyl bromides have been known for well over 099 years\ their appearance in theliterature is quite rare\ and they do not seem to have any uses unique to themselves[

"i# Preparation of N!monosubstituted carbamoyl bromides from isocyanates and hydro`en bromide

This is the only important general synthetic method for N!monosubstituted carbamoyl bromides\RNHCOBr^ it can also be used to prepare the parent unsubstituted carbamoyl bromide\ H1NCOBr\which can be isolated as a pure solid\ m[p[ 16>C\ but is of very limited thermal stability[ Examplesof compounds prepared by this route are shown in Table 3[ Both N!aryl! and N!alkylcarbamoylbromides can be prepared by this method^ a\b!unsaturated isocyanates add a further molecule ofhydrogen bromide to form a!bromoalkylcarbamoyl bromides "Equation "13## ð79AG"E#190Ł[

R2

R1 X

NHCOXR2

R1

N • O

2 HX

X = Cl, Br, I(24)

Table 3 Reaction of isocyanates with hydrogen bromide[

RNHCOBrN • OR + HBr

H 40CB177

Me 64CB3162

Et 1866BSF435

Ph 1895MI 614-01

Ref.R

"ii# Preparation of N\N!disubstituted carbamoyl bromides

"a# Preparation from carbamoyl chlorides and hydro`en bromide[ Dimethylcarbamoyl chlorideundergoes halogen exchange with hydrogen bromide at room temperature without solvent to givedimethylcarbamoyl bromide in 89) distilled yield ð48CCC659Ł[ Presumably this method could beextended to the preparation of a wide range of N\N!disubstituted carbamoyl bromides[

"b# Preparation from N\N!disubstituted formamides[ N!Formylpiperidine is converted intopiperidine!N!carbonyl bromide in 11) yield by the reaction of phosphorus"III# chloride andthionyl bromide ð60CB858Ł[ In common with the preceding method\ this is likely to be of somegenerality for preparing N\N!disubstituted carbamoyl bromides[

"c# Preparation from secondary amines and carbonic dibromide[ Although this method has an

342One Halo`en

obvious analogy with the preparation of N\N!disubstituted carbamoyl chlorides from secondaryamines and phosgene\ it has not been used to prepare the bromine analogues[ This is principallybecause carbonic dibromide is not readily accessible[

"iii# Other methods of preparin` N!bromocarbonyl compounds

In common with many other isocyanates\ ~uorocarbonyl isocyanate\ FCONCO adds hydrogenbromide to give iminodicarboxylic acid bromide ~uoride\ FCONHCOBr\ as a hygroscopic solidthat is unstable in air ð62CB0641Ł[ Radical bromination of methyl isocyanate initially gives tri!bromomethyl isocyanate\ Br2CNCO\ which rapidly equilibrates with its isomer\ bromocarbonylisocyanide dibromide\ Br1C1N!COBr[ Radical bromination of neopentyl isocyanate follows thesame course\ resulting in a tautomeric mixture of ButCBr1NCO and ButCBr1NCOBr ð71CB759Ł[A similar tautomerism is observed when benzophenone imine\ Ph1C1NH reacts with oxalylbromide\ with loss of carbon monoxide\ to give a mixture of Ph1C1NCOBr and Ph1BrCNCOð60ZOR1118Ł[

Bromine will cleave thiol ester functions in the same manner as observed for chlorine^ thus\ thecyclic disul_de "83# and thiolcarbamate "84# both yield bis"bromocarbonyl#methylamine on treat!ment with bromine "Scheme 41# ð57FRP0406268\ 64GEP1240445Ł[ Formation of N!bromocarbonylcompounds from the corresponding N!~uorocarbonyl compounds by halogen exchange has alsobeen reported^ thus\ "85# on treatment with aluminum"III# bromide gave the bromocarbonyl deriva!tive "86# "Equation "14## ð62GEP1020678Ł[ Treatment of 3!bromo!2!arylsydnones bearing an ortho!carbonyl function in the aryl group "87# with bromine or hydrogen bromide leads to 0!bromo!carbonylindazoles "88#[ The reaction tolerates a wide variety of carbonyl functions\ and usuallyproceeds in high yield "Equation "15## ð82TL128Ł[

S

SNMe

O

O

NMe

COBr

COBr

(94)

N

O

COBr

SMe

Me

(95)

Br2 Br2

Scheme 52

Cl2FCSNRCOFAlBr3

(96)Cl2FCSNRCOBr

(97)

(25)

NN

COR

NN

O

Br

O–

R

COBr

Br2, hν or HBr

39–89%

(98) (99)

R = H, Me, CH2Br, CBr3, Ph, OMe, OEt, NHMe

(26)+

"iv# N!Bromocarbonyl isocyanate and isothiocyanate

N!Bromocarbonyl isocyanate\ BrCONCO\ has been prepared by the reaction of commerciallyavailable chlorocarbonyl isocyanate with boron tribromide ð80ZAAC"599#034\ 81SA"A#0068Ł[ The sulfuranalogue\ bromocarbonyl isothiocyanate\ was prepared 09 years previously by the same route aschlorocarbonyl isothiocyanate\ by thermal decarbonylation of oxalyl bromide thiocyanate\ BrCO!CONCS\ at 74>C in the presence of active carbon in 35) yield[ The compound is a distillable oil\stable at −07>C for more than 0 week ð70CB0635Ł[


5[03[2[2[3 Carbamoyl iodides\ R0R1NCOI

Only one instance of relatively stable carbamoyl iodides has been reported[ When a\b!unsaturatedisocyanates are treated with two equivalents of hydrogen iodide\ a!iodoalkylcarbamoyl iodides areformed "Equation "16## ð68EUP6387\ 79AG"E#190Ł[ Thus\ it appears that the stability of carbamoyliodides is such that more examples could perhaps be prepared[ By analogy with iodoformates\ROCOI "see Section 5[03[2[0[3#\ similar stabilising features could be incorporated to enable isolation[

(27)R I

NHCOI

R

N • O

R = H, Me (m.p. 10 °C, 77%), Et

2 HI

–50 °C

5[03[2[3 One Halogen and One Phosphorus Function

5[03[2[3[0 Chlorocarbonyl derivatives of phosphorus"III#

The reaction of trimethylsilylphosphines with one equivalent of phosgene gives rise to intermediatechlorocarbonyl phosphorus"III# compounds[ In the case of t!butyltrimethylsilylphosphine\ButPHTMS\ this intermediate\ ButPHCOCl "099#\ is stable at low temperatures\ but loses carbonmonoxide on warming[ Treatment with base leads to the phosphaketene ButP1C1O\ which isstable below −59>C\ and adds hydrogen chloride to regenerate the chlorocarbonyl derivative"099# ð72TL1528Ł[ The analogous reaction with t!butylbis"trimethylsilyl#phosphine gives the similarintermediate "090#^ however\ this loses TMS!Cl at −89>C to give the same phosphaketene[ WhenButP"TMS#1 is treated with two equivalents of phosgene\ the reaction follows a di}erent course\through the chlorocarbonyl compound "091#\ which was characterised at −39>C by 20P NMRspectroscopy\ to t!butyldichlorophosphine\ ButPCl1 ð72CB098Ł[ These transformations are sum!marized in Scheme 42[ Mesitylbis"trimethylsilyl#phosphine "092# reacts with phosgene via the uniso!lated chlorocarbonyl intermediate "093#\ which eliminates TMS!Cl to a}ord the stablephosphaketene "094# "Scheme 43# ð72AG"E#674Ł[

TMS

ButP

TMS

COCl

ButP

TMS

(101)

O-TMS

PBut

(102)

ClOC

ButP

COCl

ButP

H

(100)

Cl

ButP

H

ButP • O

Cl

ButP

Cl

TMS

ButP

H

COCl2

–CO

–HCl

–90 °C

–TMS-ClCOCl2

2 COCl2

+HCl

Scheme 53

5[03[2[3[1 Chlorocarbonyl derivatives of phosphorus"V#

Only one compound of this type has been reported in the literature^ "dimethoxyphosphinyl#formylchloride "MeO#1P"O#COCl "095# was characterized as a stable\ distillable liquid\ prepared by the

344One Halo`en

But

But

P(TMS)2

But

But

But

P

But

But

But

P

But

TMS

COCl

• O

(103) (104) (105)

Scheme 54

Arbuzov reaction of trimethyl phosphite with phosgene "Equation "17#\ R�Cl# ð46IZV37Ł[ In viewof the fact that a simple\ functionalised derivative such as "095# would be expected to have been thesubject of further investigations\ this report must be treated with some caution^ however\ theArbuzov reaction of trimethyl phosphite with aliphatic acid chlorides to yield stable a!keto!phosphonic acid dimethyl esters has also been described "Equation "17#\ R�Me# ð34BAU253Ł\ sothe analogous reaction with phosgene to yield "095^ R�Cl# would not be surprising[

(MeO)3P + RCOCl

O

(MeO)2PCOR

R = Cl, Me

(28)

(106)

5[03[2[4 One Halogen and One As\ Sb or Bi Function

Preparations of these classes of compound have not been reported[

5[03[2[5 One Halogen and One Metalloid "B\ Si or Ge# Function

Preparations of these classes of compound have not been reported[

5[03[2[6 One Halogen and One Metal Function

Metal complexes containing a metalÐhalocarbonyl bond have been reported in all three transitionmetal series\ but not for the lanthanides or actinides[ The stability of these complexes variesconsiderably\ the most stable being isolable solids\ una}ected by air^ most are intermediates of verylimited stability\ or unexpected products of little importance[

5[03[2[6[0 Halocarbonyl complexes of _rst transition series metal "iron and chromium#

"i# Iron complexes

Pentacarbonyl iron has been reported to form an iodocarbonyl iron intermediate on reactionwith iodine ð57JOM"02#300Ł[ Subsequently\ tricarbonyl"cyclohexadienyl#iron cation has been shownto give a similar iodocarbonyl complex "096# on treatment with tetraethylammonium iodide inacetone or methyl nitrite with the exclusion of light[ It can be isolated in admixture with a secondproduct\ where the cyclohexadiene ring has been iodinated[ It is stable in the absence of light andhas an iodocarbonyl C1O stretching frequency in the IR spectrum at 0624 cm−0 "Equation "18##ð75JOM"201#C10Ł[

Fe+

COOC CO

Fe

COOC COI

Et4NI

(107)

(29)


"ii# Chromium complexes

When a mixture of tricarbonyl"benzene#chromium and a sterically hindered nitroso compoundare subjected to photolysis in carbon tetrachloride\ the chlorocarbonyl chromium complex "097# isformed "Equation "29## ð73MI 503!90Ł[

Cr

COOC CO

Cr

NOC COCl

RN O, hν

R O

R = But,

But

But

But

(30)

(108)

CCl4

5[03[2[6[1 Halocarbonyl complexes of second transition series metals "ruthenium and rhodium#

"i# Ruthenium complexes

When Ru2"CO#01 and bis"triphenylphosphine#nitrogen chloride are stored in THF for 0 h at roomtemperature\ the dark redÐbrown solution formed contains the chlorocarbonyl ruthenium complex"098#\ which is not isolated\ but can be characterized by IR spectroscopy\ the chlorocarbonyl C1Ostretching frequency occurring at 0665 cm−0 ð76JA5904Ł[

Ru(CO)4(OC)4Ru

Ru

OC COCOClOC

(109)

"ii# Rhodium complexes

A stable chlorocarbonyl rhodium complex is formed when "009# is treated with oxalyl chloride intoluene at room temperature "Equation "20##[ The yellow precipitate of "000# is stable in airð58JOM"08#050Ł[ The chlorocarbonyl C1O stretching frequency is at 0579 cm−0[ A second stablecomplex "001# is formed from the reaction of bis"cyclooctene#chlororhodium with acrolein and 0\1!bis"diphenylphosphino#ethane ð63NKK621Ł[

RhI

PPh

Ph

PPh3Ph3P

(110)

PRh

Cl

OC

(111)Ph3P

ClOCPh

Ph(COCl)2, RT

(31)

Rh

Ph3PPPh3

COCl

CHO(112)

346One Halo`en

Another chlorocarbonylrhodium complex appears in Chemical Abstracts^ however\ this is a caseof ambiguous naming\ as the chlorine and carbonyl functions are individually bonded to rhodiumð57IS88\ 61CL372Ł[

5[03[2[6[2 Halocarbonyl complexes of third transition series metals "rhenium and iridium#

"i# Rhenium complexes

Bromination of tricarbonyl"cyclopentadienyl#rhenium"I# leads to an intermediate bromocarbonylrhenium complex "002# which can decarbonylate to the _nal product "003# "Scheme 44# ð76IZV0560Ł[

ReI

COOC CO

Re

CO

OCCOBr

Br Re

CO

OCBr

Br

(113) (114)

Br2 –CO

Scheme 55

"ii# Iridium complexes

A series of ~uorocarbonyl iridium"III# complexes have been prepared by the reaction of xenondi~uoride with a range of pentacoordinate iridium"I# cations[ Most of these complexes are stable atroom temperature[ Extensive structural studies have been carried out\ including an x!ray charac!terisation[ The ~uorocarbonyl C1O stretching frequency for "004# is at 0645 cm−0[ This work issummarised in Scheme 45 ð77CC418\ 82JCS"D#0920Ł[

L

Ir CO

L

OC

OC

L

Ir

L

OC

OC

F

COF

L

Ir CO

L

Cl

OC

L

Ir

L

Cl

F

CO

COF

L

Ir

L

OC

F

Cl

COF

L

Ir CO

L

L

L

+ L

Ir

L

L

L

XeF2, 0 °C

+

XeF2, –20 °C

+

F

COF

+

L = PMe3

XeF2, –60 °C

L = PMe3

+

L = PMe3 (115), PEt3, PMe2Ph, PEt2Ph, PEtPh2

1:3

Scheme 56


6.15Functions Containing aCarbonyl Group and at Least OneChalcogen (but No Halogen)HEINER ECKERT and ALFONS NESTLTechnischen Universitat Munchen, Garching, Germany

5[04[0 CARBONYL CHALCOGENIDES WITH TWO SIMILAR CHALCOGEN FUNCTIONS 359

5[04[0[0 Two Oxyèn Functions 3595[04[0[0[0 Dialkyl carbonates from phosène and substitutes 3595[04[0[0[1 Dialkyl carbonates from inorànic carbonates 3515[04[0[0[2 Dialkyl carbonates from urea derivatives 3525[04[0[0[3 Dialkyl carbonates from carbon oxides and alcohols 3525[04[0[0[4 Dialkyl carbonates from formates and ketones 3555[04[0[0[5 Cyclic carbonates and transesteri_cation 3565[04[0[0[6 Dialkyl carbonates by iodolactonization 3575[04[0[0[7 Acyl carbonates 3585[04[0[0[8 Carbonates by electrochemistry 3585[04[0[0[09 Carbonates via ozonolysis 3585[04[0[0[00 Carbonates by miscellaneous methods 3585[04[0[0[01 Monoalkyl carbonate complexes 3695[04[0[0[02 Polycarbonates 369

5[04[0[1 Two Sulfur Functions 3605[04[0[1[0 Dialkyl dithiocarbonates from phosène and COS 3605[04[0[1[1 Dialkyl dithiocarbonates by thioneÐthiol rearranèment 3605[04[0[1[2 Dialkyl dithiocarbonates by ð2\2Ł!si`matropic rearranèment 3615[04[0[1[3 Other methods 362

5[04[0[2 Two Selenium Functions 363

5[04[1 CARBONYL CHALCOGENIDES WITH TWO DISSIMILAR CHALCOGENIDEATOM FUNCTIONS 363

5[04[1[0 Oxyèn and Sulfur Functions 3635[04[1[0[0 Dialkyl thiocarbonates from activated carbonates 3635[04[1[0[1 Dialkyl thiocarbonates from alkoxycarbonyl sulfenyl chlorides 3675[04[1[0[2 Dialkyl thiocarbonates from orthoformates 3675[04[1[0[3 Dialkyl thiocarbonates from ethyl xanthate potassium salt 3675[04[1[0[4 Miscellaneous thiocarbonates from carbonothioic acid salts 3685[04[1[0[5 Other methods 3795[04[1[0[6 Alkoxycarbonyl protectin` `roups for sulfur!containin` amino acids 379

5[04[1[1 Oxyèn and Selenium or Tellurium Functions 3705[04[1[2 Other Dissimilar Chalcoènide Functions 371

5[04[1[2[0 Oxyèn and selenium functions 3715[04[1[2[1 Oxyèn and tellurium functions 3715[04[1[2[2 Sulfur and selenium functions 371

5[04[2 CARBONYL CHALCOGENIDES WITH A CHALCOGEN FUNCTION AND ONEOTHER HETEROATOM FUNCTION 372

5[04[2[0 Oxyèn and Nitroèn Functions 3725[04[2[0[0 Urethanes from chloroformates 372

348

359 Carbonyl Group and at Least One Chalcoèn

5[04[2[0[1 Urethanes from dialkyl carbonates 3735[04[2[0[2 Urethanes from urea 3735[04[2[0[3 Urethanes from isocyanates 3735[04[2[0[4 Urethanes from isocyanides 3745[04[2[0[5 Oxazolidones "cyclic urethanes# 3745[04[2[0[6 N!Carboxy a!amino acid anhydrides 3755[04[2[0[7 Urethanes as protection for amino functions 3755[04[2[0[8 Polyurethanes 3775[04[2[0[09 Carbazates 3775[04[2[0[00 Azidoformates 378

5[04[2[1 Oxyèn and Phosphorus Functions 3785[04[2[1[0 Phosphinecarboxylates from alkali metal phosphides and carbon dioxide 3785[04[2[1[1 Phosphinecarboxylates by the Arbuzov reaction and related methods 389

5[04[2[2 Oxyèn and Other Heteroatom Functions 3805[04[2[2[0 Oxyèn and boron functions 380

5[04[2[3 Sulfur and Nitroèn Functions 3815[04[2[3[0 Thiocarbamates from chlorothioformates and amines 3815[04[2[3[1 Thiocarbamates from carbamoyl chlorides and thiols 3825[04[2[3[2 Thiocarbamates from isocyanates and thiols 3835[04[2[3[3 Thiocarbamates from 0!chlorothioformimidates 3835[04[2[3[4 Thiocarbamates from alkylamide salts\ carbon monoxide\ and sulfur 3835[04[2[3[5 Thiocarbamates by ð2\2Ł!si`matropic rearranèment 3845[04[2[3[6 Thiocarbamates from 1!dialkyliminium!0\2!oxothiolane iodides 3855[04[2[3[7 Thiocarbamates as amine protective `roups 3855[04[2[3[8 Thiocarbamates by other methods 385

5[04[2[4 Sulfur and Phosphorus Functions 3865[04[2[5 Other Mixed Systems 386

5[04[2[5[0 Selenium and nitroèn functions 3865[04[2[5[1 Tellurium and nitroèn functions 387

5[04[0 CARBONYL CHALCOGENIDES WITH TWO SIMILAR CHALCOGENFUNCTIONS

5[04[0[0 Two Oxygen Functions

5[04[0[0[0 Dialkyl carbonates from phosgene and substitutes

Carbonic acid is principally a difunctional carboxylic acid\ therefore there are many preparativemethods which provide access to a great variety of its organic derivatives and which di}er widelyin rate and selectivity of reactions and reagents[

Phosgene ð53CRV534\ 62CRV64\ B!80MI 504!90Ł\ as the formal carboxylic acid dichloride of carbonicacid\ is a highly reactive reagent which a}ords high turnovers and good yields[ Thus\ both sym!metrical and unsymmetrical dicarbonates\ the latter via chloroformates\ can easily be produced[

Generally phosgene is blown into the reacting alcohol at temperatures of about 49Ð79>C[The reaction runs at lower temperatures in the presence of acid acceptors such as amines or

inorganic hydroxides[ It can also be accelerated catalytically with N\N!dialkylamides or quaternaryammonium salts\ particularly the adduct of two moles of pyridine and one mole of phosgene\ whichcan also be isolated[ Instead of alcohols and phenols\ the corresponding alcoholates and phenolatescan be reacted with phosgene[

The manufacture of diethyl carbonate from phosgene and ethanol with a purity of 88[8) isdescribed in a patent ð75JAP50007238Ł[

The phosgenation of alcohols can be carried out in a one!step as well as in a two!step process"Scheme 0#[

O

R1O Cl

O

Cl ClR1 OH +

O

R1O OR2+ HCl

O

R1O ClR2 OH +

+ HCl50–80 °C

50–80 °C

Scheme 1

350Two Similar Chalco`ens

The advantages of the two!step process for producing diethyl carbonate in technical plantshave been described ð83JAP95930908Ł[ The greatest advantage of this process is formation of theintermediate chloroformate\ which allows the preparation of a great number of mixed esters ofcarbonic acid in a well!de_ned way[

In a similar manner to that described for reactions of phosgene\ chloroformate esters react eitherwith alcohols under re~ux or in the presence of amines such as dimethylaniline or pyridine[ Herealso crystalline adducts of one mole of chloroformate ester and two moles of pyridine can beisolated[ Alkali alcoholates also react with success[

A useful building block for palladium!catalyzed carbonÐcarbon bond formation by conversionof the carbonic acid ester into a carbon acid ester is methyl propargyl carbonate\ which can beprepared from methyl chloroformate and propargyl alcohol in high yield "Equation "0## ð82S0098Ł[Even the lithium acetylide derived from this building block is stable under the reaction conditionsrequired for further C0C connections\ as shown in a stereoselective synthesis of the side chain ofglaucosterol ð76T4204Ł[

O

O OMeO

MeO Cl

OH

+pyridine

Et2O, RT, 3 h82%

(1)

Similar substituted 1!alkyl carbonates are used in a synthesis of 0\1!dien!3!ynes ð80JOM"306#294Ł[A structurally related carbonate with a terminal ethynyl group is prepared according to Equation "1#[It is a key intermediate in the preparation of "¦:−#!pentalenolactone "E#!methyl ester ð80HCA354Ł[Reduction of geranylacetone to the corresponding alcohol and conversion into the methyl carbonatea}ords a juvenile hormone analogue "III# ð77ZN"B#0927Ł[

CHOOCO2Me

MgBr i, ii, ClCO2Me

95%(2)

The conditions required to form the carbonate from an alcohol and methyl chloroformate are somild that allenes are stable and not subject to rearrangement as shown in Equation "2# ð89TL4518Ł[Optically active alcohols react with retention of con_guration "Equation "3## ð77JOC3308Ł[ Ninedi}erent alkyl allyl carbonates were prepared from allyl chloroformate and the correspondingracemic alcohols with _nal racemic resolution ð82T09614Ł[

ClCO2Me•

R1

R2

HO

•

R1

R2

MeO2CO

(3)

Ph

O

O

OMePh

OH+

Cl

O

MeO

pyridine(4)

In 0889 Olofson and co!workers reported the _rst synthesis of O!butadienyl carbonates derivedfrom a\b!unsaturated aldehydes[ Treatment of crotonaldehyde with KOBut in THF at −67>Ca}ords the enolate\ which is converted to the carbonate by treatment with the chloroformate"Scheme 1#[ If the aldehyde bears a substituent in the a!position the "E#!butadienyl carbonates areformed exclusively ð89TL0394Ł[

O OR

OO– K+O KOBut Cl OR

O

58–83%

Scheme 2

R = Et, neopentyl, allyl, CH2CCl3


Trialkylsilyl enol ethers react well with ~uoroformates in the presence of a catalytic amount ofPhCH1NMe2

¦F− "btaf#[ The enolcarbonate from 1!methylcyclohexanone is formed in this way ingood yield as illustrated in Equation "4# ð79TL708Ł[

OCO2Et

+ TMS-F

O-TMS

+

O

EtO F

btaf (cat.)

90%(5)

btaf = benzyltrimethylammonium fluoride

This method cannot be used for enolate or silyl enol ethers derived from aldehydes because ofaldol or Michael condensation with another molecule of aldehyde[ To solve this problem\ aldehydesare treated with HF in the presence of an 07!crown!5 catalyst[ The enolates are generated and canbe trapped e.ciently as formed with ~uoroformates to give vinylic carbonates[ Fluoroformates canbe prepared by halide exchange from the chloroformates and two equivalents of KF "Scheme 2#ð89JOC0Ł[

O–R1

R2

+ KHF2

O

R2

R1

Scheme 3

+ F – + KF

+ OR3OR1

O

R2

O–R1

R2 OR3F

O+ F

–

In all the reactions so far described\ phosgene is the basic chemical used for the preparation ofcarbonates in a direct way as well as being used in the synthesis of the chloroformates[ To avoid thedi.culties associated with the toxicity of phosgene\ substitutes for phosgene have been developedðB!80MI 504!90Ł[ The liquid trichloromethyl chloroformate "diphosgene# was introduced by Kuritaand co!workers and by Ugi and co!workers ð65JOC1969\ 66AG"E#148Ł[ Much safer in storage\ trans!portation and handling is the crystalline bis"trichloromethyl# carbonate "triphosgene#\ which wasintroduced by Eckert in 0876 ð76AG"E#783\ 89MI 504!91Ł[ Since then\ triphosgene has become well!established for industrial use[ Bis"trichloromethyl# carbonate itself is a dialkyl carbonate and isprepared by radical chlorination of dimethyl carbonate in excellent yield up to 88)[

Carbonate esters 03C!labeled at the carbonyl group can be synthesized by a method utilizing thereadily available "03C#phosgene\ which is _rst converted to an isolable alkyl or aryl chloroformateand subsequently reacted with the appropriate alcohol to give the corresponding esterð75MI 504!90Ł[

5[04[0[0[1 Dialkyl carbonates from inorganic carbonates

Carbonic acid esters can be prepared in phase!transfer catalyzed reactions from primary alkylhalides and a mixture of dry potassium hydrogen carbonate and dry potassium carbonate innonpolar solvents[ The conversion is ine}ective in the absence of hydrogen carbonate and catalyst[This method uses methyltrioctylammonium chloride as catalyst and toluene or petroleum ether assolvent\ forming symmetric dialkyl carbonates in a one!step process with alkyl groups C5ÐC05 inyields of 56Ð75)[ The unsymmetrical benzyl hexyl carbonate is obtained by reacting dry potassiumhydrogen carbonate with benzyl bromide followed by reaction with dry potassium carbonate andhexyl bromide\ yielding 23) of product ð70CB0109Ł[ In a related publication the e}ect of variationof the phase!transfer catalyst is described ð73JOC0011Ł[

Dialkyl carbonates are also easily prepared by the heterogeneous reaction of solid potassiumcarbonate with alkyl bromides in DMF or DMSO in the presence of organostannyl compoundssuch as hexabutyldistannoxane or chlorotributylstannane[ A mixed catalytic system consisting of atributylstannyl compound and 07!crown!5 was e}ective even in less polar solvents[

Well!known phase!transfer catalysts such as 07!crown!5 or benzyltriethylammonium chloridewere slightly e}ective but not su.ciently so for this heterogeneous reaction[ It was found by the


authors that the reaction was distinctly accelerated by the addition of triorganostannyl compounds\especially tributylstannyl compounds\ while the tetrabutyl and dibutyl compounds were not active[DMF and DMSO were good solvents for this reaction[ Alkyl bromides were more e}ective reagentsthan the corresponding chlorides or iodides "Equation "5## ð70CL638Ł[

RO OR

OK2CO3 + 2RBr

cat.+ 2KBr (6)

5[04[0[0[2 Dialkyl carbonates from urea derivatives

A laboratory method for dialkyl carbonates makes use of 0\0?!carbonylbis"3!benzylidene!0\3!dihydropyridine# as a reagent "Equation "6## ð79S374Ł[ The required activation energy for thisreaction is delivered by the aromatization energy from the 0\3!dihydropyridine system to the 3!substituted pyridine[

O

N N

N+ 2

O

ButO OBut

THF, 25 °C+ 2ButOH

(7)

5[04[0[0[3 Dialkyl carbonates from carbon oxides and alcohols

Strong bases readily absorb carbon dioxide[ This fact is exploited in the synthesis of carbonateswith at least one tertiary alkyl group[ In a two!step process the sodium alcoholate of t!butanolreacts with carbon dioxide to form the stable sodium t!butyl carbonate which reacts with methyl orethyl iodide to the corresponding mixed carbonates "Scheme 3# ð60ZOR162Ł[

O

ButO OR+ NaI

O

ButO O– Na+ButOH + Na + CO2

6 h, reflux RI, DMF

R = Me, Et

Scheme 4

The reaction with carbon dioxide is also carried out with acetylenic alcohols catalyzed by cobalt!ocene "CoCp1#[ a!Ethynyl tertiary alcohols such as 1!methyl!2!butyn!1!ol undergo cycloadditionwith CO1\ yielding a!methylene cyclic carbonates in good yield in the presence of CoCp1 andtriethylamine[ In general the reaction is carried out in a temperature range of 79>C to 099>C\ givingyields from 71) to 76) depending on the alcohol "Equation "7##[ Propargyl alcohol\ an a!ethynylprimary alcohol\ a}ords dipropargyl carbonate in only 5) yield and a!"0!alkynyl# tertiary alcoholsdo not react with carbon dioxide[ It can be presumed that cobaltocene is oxidized to the cobalt!ocenium ion ðCoCp1Ł¦ in the presence of water or alcohol if air is present[

R2

R1

OH + CO2

CoCp2

NEt3O O

O

R2

R1

(8)

R1 = Me, EtR2 = Me, Et, Bui

R1 ≠ R2

Another method for obtaining symmetrical carbonates from CO1 and alcohols uses triphenyl!phosphane and diethyl azodicarboxylate "dead#[ The authors obtained dipentyl carbonate in 77)


yield by this route\ di!s!butyl carbonate in 79) yield\ bis"1!ethylhexyl# carbonate in 63) yield\ anddiallyl carbonate in 64) yield "Equation "8## ð71JOC4198Ł[

2ROH + CO2 + Ph3P + deadO

RO OR+ Ph3P O + EtO2C

HN

NH

CO2Et (9)

dead = diethyl azodicarboxylate

The _rst step of the reaction is the formation of monoalkyl carbonate ion from the alcohol andCO1[ The presence of triethylamine increases the amount of the ion[ The monoalkyl carbonate thenundergoes cyclization in the presence of cobaltocene as shown in Scheme 4 ð76BCJ0193Ł[

O O

O

CoII

O O

O

CoCp2

protonolysis

Scheme 5

OH + CO2 + NEt3O O

O–

[NHEt3H]+

Carbon monoxide alkoxylation reactions have been described[ CO is a low!cost product obtainedin many industrial processes and is a good ligand for transition metals^ transition metal catalyzedreactions are therefore obviously possible[ In the late 0859s\ Saegusa and co!workers described amethod for producingdimethyl carbonate[ This preparation is carried out by reaction between cupricmethoxide and carbon monoxide in pyridine as solvent[ It may be assumed that MeOCOCuOMe is_rst formed by the insertion of carbon monoxide into the copperÐoxygen linkage^ this then decom!poses to produce dimethyl carbonate "Scheme 5# ð57TL720Ł[ This reaction depends strongly on thetemperature and reaches its optimum at 69>C[

O

MeO OMe

O

MeO–Cu OMe

COCu(OMe)2

Scheme 6

In a similar process\ carbonylation of 0!propanol and 0!butanol in the presence of equivalentamounts of CuCl1 under a pressure of 19Ð099 atm of CO at 59>C yielded in the correspondingcarbonates dipropyl carbonate "71)# and dibutyl carbonate "53)#[ At temperatures above 099>Cthe proportion of the corresponding alkyl formates increases distinctly ð62IZV796Ł[ Nefedov andSergeeva in a series of three publications describe access to symmetrical and unsymmetrical car!bonates in one! or two!step processes using mercury"II# acetate[ The reactions are carried out in anautoclave with a CO pressure of 099 atm and temperatures of 199Ð119>C[ The formation of thecarbonates is described from the following alcohols\ the yield of the carbonate being given inparentheses] methanol "23)#\ ethanol "26)#\ 0!propanol "33)#\ 1!propanol "20)#\ 0!butanol"40)#\ 1!methyl!0!propanol "37)#\ 2!methyl!0!butanol "27)#\ 0!hexanol "33)#\ and 0!heptanol"31)# "Scheme 6# ð61IZV0524\ 61IZV1622\ 62IZV451Ł[

O

RO Hg OMe

O+ MeCO2H

O

MeO Hg OMe

O

+ Hg + MeCO2H+ ROH

+ CO + ROH

O

RO OR

O

RO Hg OMe

O

Scheme 7


All the methods described above use transition metal"II# salts as oxidizing agents[ Another reagentfor the oxidation is selenium[ Using a temperature of 19>C and 0 atm of CO\ carbonates frommethanol\ ethanol\ 0!propanol\ and 0!butanol were prepared in yields ranging from 83) to 88)[Benzyl alcohol a}ords the corresponding carbonate under these conditions in 65) yield[ Withsecondary alcohols such as 1!propanol and cyclohexanol\ and with t!butanol\ yields are 5) to 05)under these conditions[ THF is e}ectively used as solvent "Scheme 7# ð60TL3774Ł[ This approach isachieved more conveniently in a catalytic cycle using oxygen as the oxidizing agent[ For thepreparation of dialkyl carbonates derived from primary alcohols under conditions as describedabove\ reactions according to Scheme 8 are achieved in excellent yields[ The intervention of carbonylselenide as an intermediate in the catalytic cycle o}ers a reasonable interpretation "path a#\ althoughthere could be another path\ in which the intermediacy of carbonyl selenide is not required "path b#ð64BCJ097Ł[

O

RO Se

O

RO Se

Se + CORO–

SeCO

Na+

–

+ –ORO

RO OR

SeCO + RONa Na+

–

+ NaSe–

Scheme 8

Se

NaSeH SeCO

O

RO SeNa+

–

(path b)

(path a)

CO

NaORO2

NaOH

ROH

(RO)2CO NaOR

Scheme 9

The commercially available and cheap di!t!butyl peroxide is used in another catalytic cycle[ Di!t!butyl peroxide is an e.cient and convenient oxidant in the copper"I# chloride!catalyzed oxidativecarbonylation of alcohols to dialkyl carbonates[ The carbonate ester synthesis can be carried oute.ciently with a stoichiometric amount of methanol and "ButO#1 by using pyridine or a substitutedpyridine as a catalyst promoter at 89Ð099>C and with CuCl as catalyst[ With 1\5!dimethylpyridine"81>C\ 49 atm#\ yields of dimethyl carbonate and t!butanol are higher than 89) "Scheme 09#ð76CC309Ł[

For the preparation of dimethyl carbonate the best combination is carbon monoxide\ methanol\and air^ a good yield of 78) is obtainable[ The catalytic system for this purpose is MnCl1ÐCuCl1ÐLiCl "9[4 ] 1[4 ] 1[4# "Equation "09## ð66IZV252Ł[

Patents for producing dimethyl carbonate\ used commercially in the synthesis of triphosgene\ anddiethyl carbonate appeared during 0881 and 0882[ The catalysts are mostly copper"I# salts\ some!times promoted by amines such as trialkylamines\ 1!hydroxypyridine\ dipyridyl\ imidazole andphenanthroline^ good results can also be achieved using Co"acac#1 as catalyst[ One patent o}ers thepossibility of producing carbonates from C0 to C09 alkanols and from C2 to C5 cycloalkanolsð81JAP93943045\ 81JAP93097654\ 81JAP93245335\ 82EUP417387\ 82EUP423434\ 82JAP94144190\ 82JAP94209533Ł[Carbonates are also produced as described in a large group of patents using similar metal catalyststo those given above and additionally the nitrous acid ester from the alcohol which is introducedinto the carbonate ð82EUP447885\ 82EUP448990\ 82EUP448101\ 82GEP3023577\ 82JAP94144086\ 83EUP470139Ł[


O

RO OR

O

ROOR

O

C2H4 + 2 ROH + 2 CO + 1/2 O2

O

RO

2 ROH + CO + 1/2 O2 + H2O

+ H2OOR

O

2 ROH + 2 CO + 1/2 O2 + H2O

Scheme 10

MeO OMe

O

CO + O2 + MeOHcat. (10)

5[04[0[0[4 Dialkyl carbonates from formates and ketones

It is reported by Kondo et al[ that selenium acts as an unusual oxidizing agent of formates in thepresence of alkoxides to a}ord dialkyl carbonates in excellent yields at room temperature undernitrogen "Scheme 00\ reaction 0#\ and the facile oxidation of the NaSeH thus formed to Se withmolecular oxygen "reaction 1# initiates a catalytic reaction "reaction 2#[ Formation of the dialkylcarbonates is not observed when formates are allowed to react with sodium alkoxide under thesame conditions in the absence of Se "Scheme 00# ð63TL792Ł[

R2O OR1

O

R2O

O+ NaSeH

R2O OR1

O

NaOR1 + H2SeNaSeH + R1OH

+ NaOR1 + Se

+ NaOHR2O

O

Se + H2OO2

+ NaOR1 + 1/2 O2Se

Scheme 11

reaction 1

reaction 2

reaction 3

In contrast to the classical BaeyerÐVilliger oxidation of ketones to esters\ no simple methodologyexists for the double oxidation of ketones to carbonates[ It is reported that the formal equivalent ofa double BaeyerÐVilliger reaction is easily accomplished under mild conditions by oxidation ofdiethyl ketals with peroxycarboxylic acid[ This facile double oxidation of ketals to orthocarbonatesprovides an e.cient method for the removal of a carbonyl function from a ketone[ In this reactionthe diethyl carbonate is formed in a yield of 49) with 07) of the orthocarbonate "Equations "00#and "01## ð71JA0658Ł[

Et Et

O EtOH, H+

Et Et

EtO OEt(11)

EtO OEt

O2 mcpba

Et Et

EtO OEt+

EtO OEt

EtO OEt(12)


5[04[0[0[5 Cyclic carbonates and transesteri_cation

Cyclic carbonates are obtained most simply by reacting phosgene with ethane!0\1!diol at roomtemperature "Equation "02## ð13JCS"014#1148Ł[ Another method makes use of sodium hydro!gencarbonate as carbonyl source and 1!chloroethanol "Equation "03## ð17GEP405170Ł[ A further gas!phase process uses ethylene oxide and carbon dioxide to produce the cyclic carbonate over charcoalat a temperature of 109>C "Equation "04## ð28GEP639255Ł[

HOOH OO

O

+ COCl2 (13)

ClOH OO

O

+ NaHCO3 (14)+ NaCl + H2O

(15)OO

O

+ CO2O

A viable alternative to the traditional method of producing dimethyl carbonate is its generationthrough transesteri_cation of ethylene carbonate with methanol "Equation "05##[ Dimethyl car!bonate is useful as a gasoline octane enhancer\ methylating agent and urethane precursor[ Thisreaction is a classical ester exchange\ subject to the general rules of acid and base catalysis[ Basesare generally more e}ective\ the equilibrium being reached more rapidly with bases which havecomparable pKb values[ E}ective soluble bases include alkali metal alkoxides\ carbonates\ bicar!bonates and phenoxides^ particularly e}ective are sodium and potassium bicarbonate ð80JMOC278Ł[Transesteri_cation is also used industrially to produce dimethyl carbonate and diethyl carbonate asshown in recent patents[ Tertiary amines\ nitrogen heterocycles such as dbu\ and quaternaryammonium groups _xed on basic anion exchangers are used as catalysts ð77JAP52127932\ 82EUP432123\83EUP472678Ł[

HOOHOO

O

+ 2 MeOHMeO OMe

O(16)+

Laufer and co!workers have investigated the di}erence between the use of phosgene and triphos!gene to generate a cyclic carbonate derived from a catechol derivative[ Treatment of equimolaramounts of 3!nitrocatechol and dmap in THF with excess phosgene "19) in toluene# consistentlyproduces o!"3!nitrophenylene# carbonate as pale yellow needles in 39Ð34) yield[ Doubling theamount of dmap did not signi_cantly alter the yield of o!"3!nitrophenylene# carbonate\ but replacingphosgene by 1:2 mole of triphosgene per mole of 3!nitrocatechol and raising the temperature to49Ð59>C improved the yield to 70) "Equation "06## ð78OPP660Ł[

(17)+ 2/3Cl3CO OCCl3

O

O

OO

O2N

THF, dmap

50–60 °CO2N

OH

OH

dmap = dimethylaminopyridine

The proper choice of protecting groups is critical in the synthesis and derivatization of prosta!glandins[ During the course of the authors| research it was necessary to produce 0\2!hydroxy!prostanoid intermediates with a base!labile protecting group[ The reaction with triphosgene gavethe 0\2!cyclic carbonate of the prostaglandins "0# "Equation "07## ð82TL284Ł[

(18)Cl3CO OCCl3

O

OO

O

HO OHpyridine, CH2Cl2


O

OO

CO2Bn

O-TBDMS

(1)

Kang et al[ have described the regioselective protection of 0\1\2!\ 0\1\3!\ and 0\1\4!triols as 4!membered cyclic carbonates with triphosgene[ The substituted 0\1\2!triol "1S\2S#!3!benzyloxy!0\1\2!butanetriol\ "S#!0\1\3!butanetriol and "1R\2S#!4!tetradecene!0\1\2!triol all react with triphosgene toa}ord the 0\1!cyclic carbonates "Equations "08#Ð"10##[ "3S\4S#!5!Benzyloxy!0\3\4!hexanetriol alsoreacts in a regioselective manner to form the 3\4!cyclic carbonate "Equation "11## ð83SC294Ł[

BnO

OH

OH

OHBnO

OH

OO

O

triphosgene(19)

OH

OH

HOOH

OO

O

triphosgene(20)

OH

HO

OO

O

triphosgene(21)

OH

C8H17

OH

C8H17

OH

BnO triphosgene(22)

OH

OO

O

BnOOH

OH

5[04[0[0[6 Dialkyl carbonates by iodolactonization

Iodocyclization of a series of homoallylic t!butyl carbonates is an e.cient and moderately erythrostereoselective method for the functionalization of homoallylic alcohols with 0\2!relative asymmetricinduction\ as shown in the example in Equation "12# ð71JOC3902Ł[

O O

O

I+

erythro10 :

O O

O

I

threo1

O O

OBut

I2 (3 equiv.), MeCN

–20 °C, 5–10 h77%

(23)

In a variation of the method\ the iodolactonization is performed on lithium alkenyl carbonates\prepared in quantitative yield by bubbling CO1 through a THF solution of lithium alkoxides at


room temperature for 0 h[ The iodolactonization reaction is carried out in homogenous THFsolution at room temperature by adding 1[1 equivalents of I1 dissolved in THF to the carbonateð71JOC3515Ł[

An important intermediate in the total synthesis of nonactin is obtained by iodolactonization of0\6!octadien!"S#!3!ol!3!t!butylcarbonate to yield 0!iodo!6!octene!1\3!diol 1\3!cyclic carbonate in acis:trans ratio of 5[4 ] 0[ Further reduction of the iodo group leads to 6!octene!1\3!diol 1\3!cycliccarbonate in 44) yield ð73JA4293Ł[ The same reaction has also been used to solve problems in verycomplex syntheses of natural products ð82JOC2692Ł[

5[04[0[0[7 Acyl carbonates

A well!established coupling reagent in peptide chemistry is the tetraethylammonium salt of anacid\ usually an N!terminal protected amino acid or a peptide\ and a chloroformate "Equation "13##[The advantage of this acyl carbonate as a coupling reagent in peptide chemistry is that it can forma peptide bond in high yield and without racemization[ The by!products are gaseous carbon dioxideand the corresponding low!boiling alcohol\ which can easily be separated from the product[ Incontrast\ the by!products generated in some other methods are often di.cult to remove[ Thiscoupling technique using acyl carbonates proved its superiority in the synthesis of encephalinanalogues ð68HCA287Ł[

R O O

O O

Cl O

O

R O– NHEt3+

OTHF

–20 °C+ (24)

5[04[0[0[8 Carbonates by electrochemistry

Carbonic acid esters can be produced by electrolysis of carbon monoxide and the correspondingalcohol in the presence of a halide electrolyte[ The latter plays a catalytic role in carbonate formation[The e.ciency of the process depends\ among other variables\ on the starting alcohol ð67MI 504!90Ł[Electrolytic carbonylation of methanol in the gas phase under atmospheric pressure at 232 K isdescribed by Otsuka et al[ The anode in this process is doped with PdCl1 and CuCl1[ The desiredproduct\ dimethyl carbonate\ is produced at 9[79 V ð83CL384Ł[ Several carbonates are also formedin low yield by the anodic oxidation of aqueous potassium butyrate ð78JCR"S#04Ł[

5[04[0[0[09 Carbonates via ozonolysis

Ozonolysis of tetramethoxyethylene leads via the ozonide to dimethyl carbonate "19Ð39)#"Scheme 01#[ Higher temperatures and a lower initial concentration of tetramethoxyethylene resultin increased yields of dimethyl carbonate ð77CJC1123Ł[ Diethyl carbonate has also been reported asa product of ozonolysis of a ketene diacetal ð81CB1382Ł[

MeO

MeO OMe

OMe

OO

O

OMeOMeMeO

MeOMeO OMe

OO3+ other by-products

Scheme 12

5[04[0[0[00 Carbonates by miscellaneous methods

Diethyl carbonate is obtained in 01) yield by the reaction of di~uorodinitromethane with sodiumethoxide and _nal hydrolysis with H1SO3 "Equation "14## ð71JGU020Ł[ Treatment of carbon disul_dewith diethoxytin yields diethyl carbonate over several steps "xanthate\ orthothiocarbonate# "Scheme02# ð67BCJ2438Ł[


EtO OEt

O

F F

O2N NO22 NaOEt +

H2O, H2SO4

12%(25)

Sn(OEt)2

CS2

EtO OEt

S

S OEt

S

EtOSn

+ EtOSnSEt

Sn(OEt)2 + (EtOSn)2S Sn(OEt)2

EtO OEt

O

EtO OEt

EtOSnS OEt

Scheme 13

5[04[0[0[01 Monoalkyl carbonate complexes

The tertiary phosphine!coordinated palladium"9# complexes Pd"styrene#L1 "L�PMe2\ PMe1Ph\PMePh1# react readily with allylic carbonates "methyl 1!methylallyl carbonate and allyl ethyl car!bonate# in THF to a}ord cationic "p!allyl#palladium complexes having an alkyl carbonate anionðp!allylPdL1Ł¦ðOCOORŁ− "R�Me\ Et#[ These complexes are extremely moisture!sensitive and reactreadily with water to give the corresponding hydrogencarbonate[ Preparation of the corresponding"p!allyl#platinum carbonates leads to analogous products "Scheme 03\ Equation "15## ð81OM060Ł[

Pt

L

L

OCO2Me

Pt

L

L

O

O

O

HPt(cod)2

+

[OCO2Me]–

+

22

+H2O

–MeOH+ 2PMe3

L = PMe3

Scheme 14

+1/2

Pd

OCO2R

L

OCO2R + PdL(26)

5[04[0[0[02 Polycarbonates

Interfacial polycondensation is currently used for the industrial production of polycarbonates[Bisphenol A is reacted with phosgene at 19Ð39>C in a two!phase mixture consisting of an aqueousalkaline phase and an immiscible organic phase[ The reaction is described in Equation "16#[

Na+ O– O– Na+Cl Cl

Ox

O O

x+

O

20–40 °C

R3N

x

x NaCl+ 2 (27)

Another method is melt transesteri_cation[ Diphenyl carbonate is transesteri_ed in the melt with


bisphenol A to form polycarbonates[ During this process phenol is removed by distillation "Equation"17## ðB!81MI 504!90Ł[

HO OHPhO OPh

On n+

190–320 °C

(28)

O On

n PhOH+ 2O

As previously described diphenyl carbonate can be obtained from dialkyl carbonates[ The poly!carbonate is prepared using high!purity starting materials "diphenyl carbonate\ bisphenol A#\improved catalyst systems\ high!viscosity reactors\ and an alternative process route ð80AG"E#0487Ł[Such a process has been described in a patent ð82EUP450252Ł[

Triphosgene has recently received attention as a substitute for phosgene owing to the developmentof ecologically more favorable\ phosgene!free production processes[ The same polycarbonate canbe obtained by reaction of bisphenol A with triphosgene in the presence of triethylamine as describedby Eckert ð76AG"E#783Ł[

5[04[0[1 Two Sulfur Functions

5[04[0[1[0 Dialkyl dithiocarbonates from phosgene and COS

Symmetrical S\S?!dialkyl dithiocarbonates are usually synthesized by reacting phosgene withthiols or their sodium salts "Equation "18## ð0761JPR"1#366\ B!51MI 504!90Ł[

Cl Cl

O+ 2 NaSR

S S

O

R R (29)

Carbon oxysul_de is a good alternative to phosgene for making symmetrical S\S?!dialkyl dithio!carbonates[ Carbon oxysul_de is prepared by triethylamine catalysis from carbon monoxide andelemental sulfur[ With triethylamine and water the reactive species triethylammonium dithio!carbonate is formed[ The latter is alkylated by alkyl halides in 52Ð099) yield "Scheme 04# ð89CL700Ł[This preparative method is straightforward and convenient^ it avoids the use of toxic phosgene andof thiols[

HS S– Et3NH+

O

RS SR

O+ 2 RX

HS S– Et3NH+

O

Scheme 15

63–100%

2 COS + H2O + Et3N

X = Cl, Br, IR = Bn, Et, Bun, Hexn, Octn, CH2=CHCH2, 4-MeC6H4CH2, 3,4-Me2C6H3CH2

+ CO2

CO + SEt3N

COS

5[04[0[1[1 Dialkyl dithiocarbonates by thioneÐthiol rearrangement

Previously described synthetic routes restrict the variety of possible products to the symmetricalones[ For mixed dialkylated dithiocarbonates R0SCOSR1 "R0�R1#\ a common method is the


thioneÐthiol rearrangement "Schoenberg rearrangement#\ which makes use of an O\S!dialkyl xan!thate R0OCSSR1 "Equation "29##[ The alcohols which are used for this xanthate synthesis varyfrom simple saturated ð70JOC2030Ł and unsaturated ð61CPB1237\ 81JOC1412Ł alkanols up to complexprecursors of natural products\ for example "¦#!milbemycin!b2 ð71JA3697\ 74CC0215Ł\ angelasidineA ð77TL3846Ł\ and kaurenoide ð70JCS"P0#0182Ł[ Xanthates can also be prepared by methylation ofpotassium O!alkyl xanthates by dimethyl sulfate "alkyl�C0ÐC7 functions# in the presence of sodiumhydrogencarbonate in water ð70S038Ł[

R1O SR2

SR1 OH + CS2 + R2 I

NaH, Na or ButOK(30)

The thioneÐthiol rearrangement "Equation "20## is a formal interchange of the thione sulfur andthe oxygen from the ester component and is principally thermally activated[ It occurs in conjunctionwith the thermal elimination and is catalyzed by acids such as TFA ð70JOC2030Ł\ by amino com!pounds "for example tricaprylmethylammonium chloride#ð70S038Ł\ 3!piperidinopyridine ð81OPP199Ł\pyridine N!oxide ð76H"15#1472\ 78CPB465Ł\ 3!dimethylaminopyridine N!oxide ð77H"16#1216Ł\ andby other species including BF2 =Et1O ð67CPB2796Ł\ AlCl2 ð62CPB593Ł\ 1\3\5!trinitroalkoxybenzenesð63TL3368Ł\ palladium\ platinum\ rhodium\ iridium ð75IJ149Ł\ and phase!transfer catalysts ð79S264Ł[Yields of 47Ð099)\ mostly in the range 69Ð79)\ are obtained[

Two!phase reactions use quarternary ammonium salts as phase!transfer catalysts[ However\ theseconditions proved inadequate in the case in which the O!alkyl group was not methyl and when bothalkyl groups were methyl\ because side reactions "hydrolysis and subsequent reactions in the main#were in competition with the rearrangement to S\S?!dialkyl dithiocarbonates[ In this cases thetricaprylmethylammonium salts are used with advantage ð79S264\ 70S038Ł[

R1O SR2

S

R1S SR2

O(31)

cat. or∆

5[04[0[1[2 Dialkyl dithiocarbonates by ð2\2Ł!sigmatropic rearrangement

These rearrangements represent important organic transformations\ especially because of thehigh stereochemical control that accompanies them[ They are induced thermally[ The followingexamples of ð2\2Ł sigmatropic rearrangements a}ord S\S!dialkyl dithiocarbonates by intramolecularalkyl migration "Equation "21## ð61CPB1237Ł[ This is a convenient method for the syntheses ofdithiocarbonates "1#\ "2# and "3# from myrtenol\ trans!pinocarveol and perillyl alcohol\ respectivelyð74JOC007Ł[ Intermediate dithiocarbonates are useful in the preparation of methyl ent!06\06\06!tri~uorokaur!04!en!08!oate and ent!05\05!di~uoro!06!norkauran!08!oic acid ð70JCS"P0#0182Ł[ The_rst synthesis of angelasidine A was accomplished in eight steps starting from farnesol[ The quar!ternary carbon atom of the agelasidine A was constructed by the successful application of thehetero!Claisen allyl xanthate rearrangement[ This methodology provides the basis for a general ande.cient route to the agelasidinine skeleton ð77TL3846Ł[

S O

R

SMe

S O

R

SMe

∆(32)

S

SMeO

S

SMeO S SMe

O

(2) (3) (4)


An important step in the total synthesis of milbemicin!b2 is also a hetero!Claisen rearrangement"Equation "22## ð71JA3697\ 74CC0215Ł[ This natural product has enormous potential as a broad!spectrum antiparasitic agent[

O

SPh

OOH

OP

O

SPh

O

OP

S

OMeS

(33)

The next two examples deal with transfer of chirality\ since ð2\2Ł!sigmatropic rearrangement is animportant tool for regioselective transformation of allylic alcohols to allylically rearranged products[This is demonstrated in the asymmetric synthesis of thiotetronic acids\ which is based upon anallyl xanthate to dithiocarbonate rearrangement "Equation "23## ð76CC0117Ł[ For this purpose b!cyclodextrin is used as a catalyst to give the product in good yield and enantiomeric excess of 35)"Equation "24## ð80TL6446Ł[ b!Cyclodextrin provides a chiral environment of an inclusion complexwith the xanthates to induce chirality[ The application of ð2\2Ł!sigmatropic rearrangements in thelate stages of synthetic sequences has\ however\ been limited by the generally elevated temperaturesthat are required to induce reaction[ For this and other reasons a number of attempts have beenmade to _nd catalysts for these sigmatropic rearrangements[ Notable among the attempts is thework of Overman ð73AG"E#468Ł\ who observed that Hg"II# and Pd"II# complexes caused accelerationsof the order of 0909 over the thermal uncatalyzed Cope rearrangements[ The overall stereochemistryof the reaction was similar to that of the corresponding uncatalyzed rearrangement ð71JA6114Ł[ Anexample of this method is shown in Equation "25# ð75IJ149Ł[

(34)OCS2Me

EtO2C EtO2C SC(O)SMe

S

RS O

*

H

O

S

SR

HO

[3,3]

2–5 °C(35)

R = Me, Et, Bn

S SMe

O

S SMe

O

O SMe

S+ (36)


Besides these classical methods\ some less common synthetic approaches have been published[Sigmatropic rearrangements normally introduce the sulfur into position three of an alkene\ but

there is an example in which sulfur is transferred from position 5 to position 0 of a terminal alkene\accompanied by the formation of a carbonÐcarbon bond "ring closure#[ The authors propose a freeradical mechanism for this isomerization of an S!methyl hex!4!enyl xanthate to an S!cyclo!pentylmethyl S?!methyl dithiocarbonate "Equation "26## ð82JOC1783Ł[


O

O

O

MeOCO

H

S SMe

O

HHO

O

O

O

HMeOCO

H SMe

S

(37)

1

23

45

6

7

8

910

111213

14

15

A variation of thioneÐthiol rearrangement starting with O!alkyl S!methyl xanthates a}ordsbis"methylthio carbonyl# poly!sulfanes "4# via sulfenyl chloride intermediates ROC"SCl#"Cl#SMeð73JCS"P0#1504\ 72JOC3649Ł[

MeS Sn SMe

O O

(5) n = 1 to 6

A method which makes no use of rearrangement and works under very mild thermal conditionsis the oxygenation of the lithio derivatives of a!phosphoryl dithiocarbonates "Equation "27##ð73TL1378Ł[

RS SMe

OO

(EtO)2P SR

LiSMe

O2

–78 °C+ (EtO)2PO2Li

R = Me, Et

(38)

b!Amino!substituted dithiocarbonates are prepared in a simple HBr!catalyzed hydrolysis ofsubstituted thiazolines "Equation "28## ð53JOC1331Ł[

O

S SNH2•HBrHBr•H2N

6 mol l–1 HBr

4 h, reflux61%

N

SS

NH2•2HBr

(39)

5[04[0[2 Two Selenium Functions

Se\Se?!Dibenzyl diselenocarbonate is prepared in 48) yield by decomposition of dibenzyl tri!selenocarbonate in the presence of an oxygen base such as potassium hydrogencarbonate\ and ofmercury dichloride "Equation "39## ð79T0340Ł[ Mechanistic studies on this reaction showed thatoxygen bases react in a classic additionÐelimination reaction\ yielding an intermediate benzyldiselenocarbonate anion[

BnSe SeBn

Se

BnSe SeBn

O80% acetone/water, reflux

KHCO3, HgCl2(40)

5[04[1 CARBONYL CHALCOGENIDES WITH TWO DISSIMILAR CHALCOGENIDEATOM FUNCTIONS

5[04[1[0 Oxygen and Sulfur Functions

5[04[1[0[0 Dialkyl thiocarbonates from activated carbonates

The dominant method for producing dialkyl thiocarbonates and bis"dialkoxycarbonyl# sul_desuses alkyl chloroformates and sul_des[

Bis"methoxycarbonyl# sul_de can be prepared by reacting methyl chloroformate and lithium

364Two Dissimilar Chalco`enides

sul_de in THF to a}ord the product in 40) yield[ Commercial anhydrous Li1S does not dissolvein THF and has to be prepared freshly "Equation "30## ð68T1218\ 67CC727Ł[

MeO Cl

O

MeO S

OTHF

51%2

OMe

O(41)+ 2 LiCl+ Li2S

These compounds may also be obtained in very high yields by the reaction of alkyl chloroformateswith sodium sul_de nonahydrate in a solidÐliquid system consisting of dichloromethane\ the above!mentioned salt\ and hexadecyltributylphosphonium bromide as phase!transfer catalyst[ A typicalprocedure consists of the slow addition of 09 mol) excess of powdered sodium sul_de to a well!stirred solution of the alkyl chloroformate and hexadecyltributylphosphonium bromide "4 mol)with respect to the sul_de# in dichloromethane at 9>C[ Bis"alkoxycarbonyl# sul_des are not formedor formed only in low yields without the catalyst[ With the catalyst\ the high yields obtained undermild conditions\ the use of cheap and common laboratory reagents\ the absence of side reactions\and the simple workup\ make this procedure useful for preparation of bis"alkoxycarbonyl# sul_des"Equation "31## ð71SC786Ł[

MeO Cl

O

MeO S

Ocat., CH2Cl2

93%2

OMe

O(42)+ 2 NaCl+ Na2S

cat. = C16H33(C4H9)3P+ Br–

The above methods deal with the reaction of alkyl chloroformates with inorganic sul_des a}ordingS!acyl thiocarbonates[ By using thiols instead of inorganic sul_des\ mixed alkyl thiocarbonates canbe formed[

An obvious route to unsymmetric alkyl derivatives of thiocarbonic acid uses alkyl chloroformates\which are obtained from the corresponding alcohol and phosgene[ Because of the toxicity ofphosgene\ chloroformates can also be prepared with advantage using triphosgene[

The previously described alkyl chloroformates react with alkanethiols to give alkyl thiocarbonates[The reaction can be used to obtain branched and unsymmetric dialkyl thiocarbonates "Equation"32## ð65BSF490Ł[ Taylor and co!workers have synthesized S!ethyl O!methyl thiocarbonate\ S!isopropyl O!methyl thiocarbonate\ and S!butyl O!methyl thiocarbonate for use in mechanisticstudies of thermal eliminations[ They all are prepared by reacting methyl chloroformate and thecorresponding thiol in the presence of pyridine to trap the HCl evolved "Equation "33##ð72JCS"P1#180Ł[

O

S

O

O

Cl

O

SH+ (43)

MeO Cl

O

MeO SR

Opyridine(44)RSH + + Py•HCl

R = Et, Pri, Bu

1!Thiomethyl!1!phenyl!0\2!indanedione is also transformed to the corresponding thiocarbonatesas described by Marshalkin et al[ by using methyl and phenyl chloroformates in the presence of thebase triethylamine\ as outlined in Equation "34# ð74ZOR0569Ł[

RO Cl

OPh

SH

O

O

Ph

S

O

O

(45)Et3N

OR

O

+

R = Me, Ph


Polyethyleneoxydiisothiocyanates can be obtained by thermolysis of the thioacyl O!ethyl thio!carbonate\ which can easily be prepared by reacting ethylene dithiocarbamate\ ethyl chloroformate\and triethylamine "Scheme 05# ð74ZOB1099Ł[

N

S S

H ON

H

SS

n

OEtEtO

OSCN

ONCS

+n

+ EtOH∆

– COS

n = 1, 2, 3, 4

Scheme 16

EtO Cl

ON

S S– NEt3+

H ON

H

S– NEt3+S

O

n

The above examples all describe a simple way to obtain the alkyl thiocarbonates[ This class ofcompounds is also used\ for example\ in the synthesis of juvenile hormone analogues ð77ZN"B#0927Ł\and as intermediates in prodrug synthesis ð89S0048Ł[ S!Ethoxycarbonyl O!ethyl dithiocarbonate canbe obtained by the Holmberg method\ which consists of the reaction of sodium O!ethyl dithio!carbonate with ethyl chloroformate using acetone or ethanol as solvent "Equation "35## ð74PS"14#80Ł[

EtO SNa

S+

EtO S

S+ NaCl

EtO Cl

O

OEt

O(46)

1!Propoxycarbonyl thiocyanate can be prepared by the reaction of isopropyl chloroformatewith a rhodanide anion ð77PS"28#146Ł[ Ethyl"methoxycarbonylthio#phenylarsine sul_de "5# can beprepared as a by!product in a yield of 16) by reacting ethylmethylphenylarsine sul_de with methylchloroformate in boiling benzene ð65JGU1330Ł[

AsS

S

OMe

O

(6)

Et

Ph

Esters of O\O!dialkyl dithiophosphoric acids are of marked interest because of their exceptionalinsecticidal properties and low mammalian toxicity[ These esters can be prepared by reaction ofO\O!diethyl dithiophosphoric acid salts with methyl chloroformate\ isopropyl chloroformate\or benzyl chloroformate to a}ord the corresponding diethyl S!alkoxy!carbonyl dithiophosphatein yields from 51) to 79) depending on the reaction conditions[ The best results are obtainedin benzene at 79>C\ but yields are also acceptable when the reaction is carried out in acetonitrileat 19>C "Equation "36## ð75CI"L#039Ł[

PS

S

OR

O

EtO

EtO

PS– Et3NH+

S

EtO

EtO

+Cl OR

O

benzeneor

MeCN(47)

R = Me, Et, Pri, Bn

S!Vinyl O!t!butyl thiocarbonate is obtained "59)# from S!"b!chloroethyl# chlorothioformate byreaction with potassium t!butoxide at −29>C[ The chloroformate can be prepared by reactingphosgene with thiirane at −09>C "Scheme 06# ð66MI 504!91Ł[

S Cl

O

ClS OBut

OKOBut, –30 °C

S Cl Cl

O

+–10 °C

Scheme 17


Thiocarbonates are also important as nonisoprenoid juvenile hormone analogues[ For example\1!"2!phenoxyphenoxy#ethanol is condensed with ethyl chloroformate\ giving S!ethyl O!1!"2!phenoxyphenoxy#ethyl thiocarbonate "Equation "37## ð78ZN"B#872Ł[

EtS Cl

O+

O OO SEt

O

O OOH

(48)

Ethyl chloroformate also reacts with nitro alcohols in the presence of anhydrous iron"III# chlorideto form the respective O!alkyl S!ethyl thiocarbonates[ The reaction proceeds vigorously at ambienttemperature\ is complete in a few minutes\ and is essentially quantitative "Equation "38## ð68S599Ł[ Itis remarkable that iron"III# chloride exhibits no catalytic e}ect with other alkoxycarbonyl chlorides[

Cl SEt

O

RO SEt

OFeCl3/CH2Cl2

–HClOH +R (49)

R = (O2N)3CCH2, FC(NO2)CH2, MeC(NO2)2CH2, O2NCH2CH2

A substitute for an S!alkyl thiochloroformate is an S!alkyl thiocarbonylimidazolium chloride[Such nitrogen!containing compounds\ for example tertiary amines or imines\ are very good acylatingco!reagents ð67T2094Ł[ Another activation of the alkyl thioformate group is provided by the cor!responding bromothioformate\ an example of which is easily derived from tri~uoromethylthio~uoroformate by halogen interchange[ This species reacts well with sodium cyanide to a}ordthe tri~uoromethyl thiocyanoformate "Equation "49## ð67CB1780Ł[

S Br

O

S CN

O(50)+ NaBrF3C F3C+ NaCN

In the case of tertiary alkyl groups the corresponding chloroformate is unstable[ In these casesactivation is provided by the carbonic acid anhydride[ Both thiophenol and butanethiol reactrapidly with di!t!butyl dicarbonate under phase!transfer conditions using the anhydrous potassiumcarbonate 07!crown!5 system\ and a}ord good yields of the corresponding t!butoxycarbonyl deriva!tives "Equation "40##[ In contrast\ the reaction with aqueous sodium hydroxide and tetra!butylammonium hydrogensulfate does not lead to product\ because the thiocarbonates areimmediately hydrolyzed back to the starting thiols ð74CJC042Ł[

ButO O

O

OBut

O+ RSH

K2CO3, 18-crown-6

RS OBut

O(51)

R = Ph, 96%; Bun, 90%

Cyclic thiocarbonates are of especial interest in the chemistry of sugars[ Methyl 1\5!di!O!methyl!2\3!O!thiocarbonyl b!D!galactoside is added to a solution of methyl iodide and propylene oxidesealed in a glass ampoule and heated to 79>C for 03 h to a}ord the iodothiocarbonates in 88)yield "Equation "41## ð76AJC684Ł[ The importance of thiocarbonates formed by reaction with chloro!formates is also documented in several patents ð70USP113665\ 72MIP7292592\ 80MIP8009528\82GEP3039335Ł[

O

OMe

OMe

OMe

OS

O

MeI, O

14 h, 80 °CO

OMe

OMe

OMe

O

O

MeS

O

OMe

OMe

OMe

IO

MeS

O

+

I

(52)


5[04[1[0[1 Dialkyl thiocarbonates from alkoxycarbonyl sulfenyl chlorides

Alkoxycarbonyl sulfenyl chlorides are highly reactive electrophilic thiocarboxylating reagents[Methoxycarbonyl sulfenyl chloride is an established reagent[ This reagent can be used to form S!aryl thiocarbonates from aromatic compounds in the presence of Lewis acids such as AlCl2 or BF2

in methylene chloride or carbon disul_de "Equation "42##[ These thiocarbonates hydrolyze inmethanolic potassium hydroxide to the aryl mercaptans in yields of 89) ð66ZC300Ł[

S OMe

O

S OMe

O+

AlCl3

70%+

ClS OMe

O

3 : 1

(53)

a!Sulfenylated ketones are also available in a regioselective a!methoxycarbonyl sulfenylationof various ketones or aldehydes employing methoxycarbonyl sulfenyl chloride[ Addition of thecorresponding ketones or aldehydes to one equivalent of the reagent in chloroform at room tem!perature for 13 h provides a!methoxycarbonyl sulfenylated carbonyl compounds in good yields[ Asan example\ the reaction of nonan!3!one is shown in Equation "43# ð81JOC0942Ł[

(54)CHCl3

74%+

ClS OMe

O

O

S

O

OMe

O

Alkanesulfenyl methyl thiocarbonates can also be obtained[ Reaction of benzyl thiol withmethoxycarbonyl sulfenyl chloride in methanol yields the disul_de "Equation "44## ð79JOC160Ł[

ClS OMe

O

Ph SH +S OMe

O

SPh (55)

The reagent methoxycarbonyl sulfenyl chloride is easily prepared by reacting methanol withchlorocarbonyl sulfenyl chloride ð77JHC082Ł[

5[04[1[0[2 Dialkyl thiocarbonates from orthoformates

O\S!Diethyl thiocarbonate is prepared by reaction of 1!ethoxy!0\2!oxathiolane with t!butyl per!oxide as radical initiator "Equation "45##[ The key step is hydrogen atom abstraction by the initiator[Under same reaction conditions\ butyl diethoxymethyl sul_de is converted into S!butyl O!ethylthiocarbonate "Equation "46## ð70ZOR0428\ 74ZOR1195\ 75JOU169Ł[ Lauryl peroxide has also been usedas initiator instead of t!butyl peroxide ð76JGU254Ł[

EtS OEt

O

O

SOEt

But2O2

120–140 °C50%

(56)

S OEt

OBut2O2

50%(57)

S OEt

OEt

5[04[1[0[3 Dialkyl thiocarbonates from ethyl xanthate potassium salt

In research on model systems for disul_de prodrug formation\ dithiocarbonates are often inter!mediates[ They are obtained by the reaction of an alkyl iodide and ethyl xanthate potassium salt[The thiocarbonate from an alkyl isoalloxazine is obtained in good yield "Equation "47## ð80JMC1938Ł[


N

N

N

N O

I

O

( )n N

N

N

N O

S

O

( )nOEt

O

EtO S– K+

O+

0 °C to RTCH2Cl2

(58)

n = 3–8

5[04[1[0[4 Miscellaneous thiocarbonates from carbonothioic acid salts

In reactions analogous to the oxidation of xanthates to dixanthogens and the oxidation ofdixanthates to tetraxanthogens\ monothiocarbonates and bis"monothiocarbonates# can be oxidizedto the corresponding disul_des[ The oxidation of potassium monothiocarbonates is performedrapidly and quantitatively using iodine "Equation "48## ð62AJC644Ł[

RO S– K+

O

S OR

O

SRO (59)I2

O

Potassium monothiocarbonates such as potassium O!ethyl thiocarbonate can act as sulfur nucleo!philes and undergo addition to electrophiles such as epoxides or alkyl halides "Equations "59# and"50## ð72JOC4922Ł[

(60)EtO S– K+

OOH

SOEt

O

+16% + by-products

O

EtO S– K+

O+ S OEt

O

Br

BrBr

S OEt

O

S OEt

O

(61)+

28% 17%

It is known that the polarizability of chalocogens depends on their position in the periodic table[In the case of charged species the counterion also plays an important role[ If the counterion ischanged to a tertiary amine\ particularly dbu\ thiocarbonates are obtained in optimum yields by S!alkylation of the ammonium salts "Equations "51# and "52# and Table 0#[ The reagent itself is easilyprepared by reacting carbon monoxide\ elemental sulfur\ and an alcohol in an autoclave in thepresence of dbu "Equation "51## ð77TL3656Ł[

R1OH + CO + Sdbu

R1O S– (dbuH)+

O

(62)

dbu = 1,5-diazabicyclo[5.4.0]undec-5-ene

R2X

R1O SR2

O

R1O S– (dbuH)+

O

(63)

The nature of the alkylating agent is also important in this type of reaction[ If iodomethaneis used\ excellent yields of products are usually obtained ð89ZOB0715Ł[ The potassium O!alkylthiocarbonate\ used as above\ can also be prepared by a selenium!catalyzed reaction of alcohol\carbon monoxide\ and sulfur to react in a second step with alkyl halides to a}ord the desiredproduct ð89TL3662Ł[

Using a potassium O!alkyl thiocarbonate\ unsymmetrical dialkoxycarbonyl sul_des are obtainedin a reaction with O!alkyl chloroformates "Equation "53## ð89S714Ł[


Table 0 Formation of unsymmetrical thiocarbonates from alcohols and alkyl halides"Equations "51# and "52##[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐAlcohol Alkyl halide Product Yielda

")#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐBunOH PhCH1Br BunOC"O#SCH1Ph 75

CH11CHCH1Br BunOC"O#SCH1CH1CH1 099BunI BuOC"O#SBun 64

MeOH PhCH1Br MeOC"O#SCH1Ph 63EtOH PhCH1Br EtOC"O#SCH1Ph 82PrnOH PhCH1Br PrnOC"O#SCH1Ph 75PriOH PhCH1Br PriOC"O#SCH1Ph 71n!C09H10OH PhCH1Br n!C09H10OC"O#SCH1Ph 70PhCH1OH PhCH1Br PhCH1OC"O#SCH1Ph 72CH11CHCH1OH PhCH1Br CH11CHCH1OC"O#SCH1Ph 60CH2OCH1CH1OH PhCH1Br CH2OCH1CH1OC"O#SCH1Ph 76ButOH PhCH1Br ButOC"O#SCH1Ph 41*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐa Isolated yields based on alcohol used[

O

R1O S OR2

O

Cl OR2

OO

R1O S– K++

acetone/H2O0 °C to RT

93–98%(64)


Ozonolysis of 0!methoxyvinyl aryl sulfones leads to S!aryl O!methyl thiocarbonate S\S!dioxidesin good yield[ The ozonolysis is carried out in ethyl acetate in the presence of tetracyanoethylene"TCNE# "Equation "54## ð65S397Ł[

MeO SO2Ar

O

MeO SO2Ar

O3, MeCO2Et, TCNE(65)

Carbamoyldisul_des are obtained by reacting O!alkyl chlorothioformates with chlorocarbonylsulfenyl chloride in the presence of phenylmethylamine followed by hydrolysis "Equation "55##ð75JOC0755Ł[

ClS Cl

O+ S NMePh

O

SRO

RO Cl

S i, PhNHMe

ii, H2OO

(66)

5[04[1[0[6 Alkoxycarbonyl protecting groups for sulfur!containing amino acids

The sulfur terminus of cysteine is protected reversibly by easily removable protecting groups ofthe thiocarbonate type[ Cysteine can also be protected simultaneously at the thiol group and at theamino function "Equation "56##[ To prevent oxidation to the disul_de\ the sodium salt of the thiolgroup is dissolved in degassed oxygen!free water ð89MI 504!90Ł[ The allyloxycarbonyl residue canalso be introduced as a side chain protection for the SH group via the chloroformate "Equation"57## ð82MI 504!90Ł[ Other protecting groups such as isobutyloxycarbonyl are similarly introducedwith success to form the thiocarbonate from sulfur!containing amino acids ð81JC130Ł[

i, Na, NH3(l), –40 °C; ii, Ph O Cl,

O

–15 °C to –5 °C, 90 min, H2O, pH 9–10

Ph O S OH

OO

NH

O

O

Ph

HS OH

O

NH H

i, ii(67)


(68)O S OH

OO

NH t-BOC

O Cl

O

HS OH

O

NH t-BOC

+H2O, pH 7.5

t-BOC = t-butoxycarbonyl

5[04[1[1 Oxygen and Selenium or Tellurium Functions

Selenocarbonates are prepared in a convenient one!pot synthesis as described by Segi et al[ Thereaction of bis"trimethylsilyl# selenide with BunLi followed by alkylation with an alkyl halide givesalkyl silyl selenides[ The repetition of a similar one!pot reaction with another mole of BunLi\ andthe appropriate chloroformate yields unsymmetrical selenocarbonates[ By this route Se!hexyl O!ethyl selenocarbonate\ Se!benzyl O!ethyl selenocarbonate and Se!hexyl O!phenyl selenocarbonatehave been prepared in yields from 22) to 64) "Equations "58#Ð"61## ð78CL0998Ł[

TMS-SeMe3

BunLi

0 °C, 30 min, THFLiSe-TMS (69)

(70)R1Se-TMS30 °C, 2 h

LiSe-TMS + R1X

(71)R1Se-TMSBunLi

0 °C, 30 minR1SeLi

R1SeLi +30 °C, 2 hO

R2O Cl

O

R1Se OR2(72)

R1 = C6H13, PhCH2R2 = Et, Ph

Alternatively\ the reaction of BunLi and selenium gives lithium n!butyl selenide[ The latter reactsin a further step with ethyl chloroformate to produce the selenocarbonate in 04) yield "Scheme 07#ð64BCJ097Ł[ Instead of the lithium salt\ a sodium alkyl selenide can be used[ It is prepared from analkyl selenol and elemental sodium[ The subsequent step is the reaction with alkyl chloroformatesas described above "Scheme 08# ð73ZAAC"402#072Ł[

Se + BunLiTHF, 0 °C

BunSeLiClCO2Et, 0 °C

15%

O

BunSe OEt

Scheme 18

R1SeH + Na–H2

R1Se– Na+ClCO2R2 O

R1Se OR2

Scheme 19

Selenocarbonates with long!chain alkyl groups are prepared by reacting didecyl diselenide\ sodiumborohydride\ and methyl chloroformate[ The tellurocarbonates can be obtained in the same wayð80JCS"P1#490Ł[

Tellurodicarbonic acid diesters are obtained as reasonably stable oily compounds by reactingalkyl chloroformates with sodium telluride\ prepared in situ from sodium hydride and tellurium in


dry DMF\ under phase!transfer conditions[ The yields of diesters range from 28) to 58) "Equation"62## ð78BCJ1006Ł[

O

RO Te OR

OO

RO Cl2 + Na2Te

R = Me, Et, Pri, Bn

(73)

5[04[1[2 Other Dissimilar Chalcogenide Functions

5[04[1[2[0 Oxygen and selenium functions

Se!Decyl O!methyl carbonate is prepared by reacting elemental selenium\ hydrazine hydrate\ and0!bromodecane to yield didecyl selenide\ which reacts in a further step with methyl chloroformateto a}ord the product in 58) yield "Scheme 19# ð80JCS"P1#490Ł[

Se OMe

O

( )9Se

Se( )9 ( )

9Se +

Br( )

9

H2N NH2

NaOHMeOH

MeO Cl

O

MeOH

Scheme 20

5[04[1[2[1 Oxygen and tellurium functions

Te!Decyl O!methyl carbonate can be prepared "29)# from elemental tellurium by its reductionwith sodium borohydride and alkylation with 0!bromodecane\ followed by further reaction withmethyl chloroformate "Equation "63## ð80JCS"P1#490Ł[ Tellurodicarbonic acid diesters can be syn!thesized by reacting alkyl chloroformates with sodium telluride in the presence of tetrabutyl!ammonium bromide[ The products tellurodicarbonic acid dimethyl!\ diethyl!\ diisopropyl!\ anddibenzyl esters are obtained in reasonable yields of 28Ð58) ð78BCJ1006Ł "Equation "64##[

Te OMe

O

( )9

MeO Cl

O

i, NaBH4, Me(CH2)9Br, DMF

ii,

Te (74)

O

RO Te OR

OO

RO Cl2 + Na2Te

R = Me, Et, Pri, Bn

(75)benzene, RT

5[04[1[2[2 Sulfur and selenium functions

S\Se!Dialkyl thioselenocarbonates are prepared in an experimental route starting with thealkylselenol\ as described by Sturm and Gattow[ Sodium ethyl selenide undergoes reaction withS!ethyl thiocarbonate to a}ord S\Se!diethyl thioselenocarbonate in 35) yield "Equation "65##ð73ZAAC"403#019Ł[

Cl SEt

O

EtSe SEt

O

46%EtSeNa + (76)

S\Se!Dialkyl thioselenocarbonates are also prepared using mercury reagents[ A typical procedureuses tri~uoromethyl bromothioformate and bis"tri~uoromethylseleno#mercury[ The mixture is

372One Chalco`en

allowed to react to 029>C over 05 h[ S\Se!Bis"tri~uoromethyl# thioselenocarbonate is obtained in80) yield "Equation "66## ð67CB1780Ł[

(77)F3CS Br

O

F3CS SeCF3

O

91%+ CF3SeHgBr+ Hg(SeCF3)2

5[04[2 CARBONYL CHALCOGENIDES WITH A CHALCOGEN FUNCTION AND ONEOTHER HETEROATOM FUNCTION

5[04[2[0 Oxygen and Nitrogen Functions

Urethanes are carbonic acid derivatives containing a carbonyl function directly connected to analkoxy function and an amino function[ They are important for producing pharmaceuticals andpolymers\ and therefore many preparative methods exist[

The formal constitution allows a great deal of variety in the alkoxy component as well as thebasic amino function[ In general two synthetic approaches to urethanes can be distinguished^ the_rst method involves a carbonic acid derivative of an alcohol or of a phenol reacting with ammoniaor an amine^ the second method involves a carbonic acid derivative of ammonia or an amine reactingwith an alcohol or a phenol[

5[04[2[0[0 Urethanes from chloroformates

Chloroformates are easily prepared using the readily available triphosgene bis"trichloro!methyl#carbonate ð76AG"E#783Ł[ Chloroformates react easily with ammonia or amines[ n!Butylchloroformate reacts in concentrated aqueous ammonia to a}ord the corresponding urethane\ theexcess ammonia absorbing the hydrochloric acid "Equation "67## ð19JCS697Ł[ This reaction canalso be carried out in organic solvents such as ether or toluene[ Of course\ half of the ammonia\ andtherefore half of the amine\ is lost as its hydrochloride^ to prevent this\ a tertiary amine\ sodiumcarbonate or sodium hydroxide is used to absorb the HCl[ For example\ ethyl N!aziridinylurethaneis prepared by reacting ethyleneimine and ethyl chloroformate in the presence of triethylamine"Equation "68## ð49LA"455#118Ł[

O Cl

O+ 2 NH3 + NH4Cl

O NH2

O(78)

EtO Cl

ON H +

Et3N, benzene

60%

O

N OEt(79)

A cancer research group in Omaha has developed a convenient method for synthesizing N!ð2HŁmethyl N!nitroso carbamate transfer reagents[ The corresponding intermediates succinimidylN!methyl carbamate "6#\ penta~uorophenyl N!methyl carbamate "7# and 0\1\1\1!tetrachloroethyl N!methyl carbamate "8# are obtained by reacting triphosgene ð76AG"E#783Ł or 0\1\1\1!tetrachloroethylchloroformate with N!hydroxysuccinimide\ penta~uorophenol\ or tetrachloroethanol with methyl!amine[ Yields vary from 24) to 85) ð80MI 504!91Ł[

N

O

O

O

N

O Me

H

(7)

F

F

F

F

F

O N

O

Me

H

(8)

O NMe

O

H

Cl3C

Cl

(9)


5[04[2[0[1 Urethanes from dialkyl carbonates

Urethanes are also available from dialkyl carbonates by partial aminolysis[ This procedure isadvantageous if mild reaction conditions are necessary[ The components\ for example\ diethylcarbonate and ethylenediamine\ are mixed and heated gently to a}ord ethyl N!1!amino!ethylcarbamate "Equation "79## ð23GEP565938Ł[

EtO OEt

O

H2NN OEt

H

O

+ H2NNH2 (80)

Urethanes are also available from cyclic carbonates[ Einhorn obtained catechol carbonic aciddiethylamide from catechol carbonate and diethylamine "Equation "70## ð0787LA"299#034Ł[

OHO

O NEt2

O

OO + Et2NH (81)

Aminolysis of ethyl isopropenyl carbonate with 1!phenylethylamine a}ords O!ethyl N!1!phenyl!ethylurethane in excellent yield[ The advantages of this method are the mild reaction conditions\the high yield\ the absence of an additional base\ and the formation of acetone as the only by!product "Equation "71## ð67TL2626Ł[

O OEt

OOEtN

O

PhNH2

H

Ph

O+ + (82)

90%

5[04[2[0[2 Urethanes from urea

Urea is suitable as a cheap starting material for N!unsubstituted urethanes[ If urea and alcoholsare heated at high temperature\ the corresponding urethanes are obtained in good yields[ In thisway carbamic acid benzyl ester can be obtained in yields of 76) by heating benzyl alcohol and ureain the presence of Zn"OAc#1 for 7 h at 049>C "Equation "72## ð35ZN"B#407Ł[ Urea salts\ especiallyurea nitrates\ can also be used to obtain the urethanes ð0788GEP003285Ł[

H2N O

O

PhH2N NH2

O+ Ph OH

Zn(OAc)2

87%(83)

5[04[2[0[3 Urethanes from isocyanates

Isocyanates react easily and mostly quantitatively with alcohols\ particularly primary alcohols\to produce urethanes "Equation "73##[ However phenolic hydroxy functions react slowly and onlyin fair yields[ For this reason\ urethanes containing phenolic groups are prepared more advan!tageously by the chloroformate route ðB!20MI 504!90Ł[

OR2NR1

O

H

R1NCO + HOR2 (84)

Urethanes can also be formed if Hofmann degradation\ Curtius degradation\ or Lossen rearrange!ment is performed in the presence of alcohols or phenols[

374One Chalco`en

The cephalosporin derivative "09# was prepared in a study of the e}ect of varying the substituentat C!2[ The urethane is prepared by reaction of the 2!desacetyl cephalosporin derivative with benzylisocyanate "77) yield# ð81JMC2620Ł[

N

S

O

O O

O N

O

H

Ph

O NMe

O

OH

MeO

(10)

5[04[2[0[4 Urethanes from isocyanides

If isobutyraldehyde and cyclohexyl isocyanide are added to a solution of n!butylamine in methanolwhich is saturated with carbon dioxide\ and the solution is then allowed to stand for 19 h at about19>C\ the urethane can be isolated in almost quantitative yield "Scheme 10# ðB!60MI 504!90Ł[ Ananalogous four!component condensation "3CC# is observed with benzylamine\ n!butyraldehyde\and cyclohexyl isocyanide[

BunNH2 + MeOH + CO2 BunNH3+ MeOCO2

–PriCHO, c-C6H11NC

BunN

OMeO

Pri

O

NH-c-C6H11N-c-C6H11

O

O

MeO

Pri

BunNH

Scheme 21

5[04[2[0[5 Oxazolidones "cyclic urethanes#

Easy access to oxazolidones is given by reacting ethanolamine with potassium cyanate in anaqueous solution to a}ord 1!hydroxyethylurea\ which cyclizes on distillation to the desired product"Scheme 11# ð92CB0179Ł[ The hydroxyethylurea can also be prepared using methods described above[

NH2N

O

H

HO

H2ONH2HO + KNCO

distil.NHO

O

Scheme 22

1!Bromoethoxycarbonyl!protected amino acids\ glycine or L!valine\ can generate 1!oxazolidoneN!acetic acid "00# or 1!oxazolidone N!isovaleric acid "01# under very strongly alkaline conditions\like 0 mol l−0 sodium hydroxide\ as described by Eckert and Ugi ð68LA167Ł[

NO

O

OH

O

(11)

NO

O

OH

O

(12)


Oxazolidin!1!ones can be prepared in a simple one!step procedure using triphosgene ð76AG"E#783Ł[L!Serine reacts with 0:2 equivalent of triphosgene at room temperature in dioxan and sodiumhydroxide to yield 56) of 3!carboxyoxazolidin!1!one "Equation "74## ð82SC1728Ł[ 1!Amino!4!methoxyphenol can similarly be converted into 5!methoxybenzoxazolinone "Equation "75##ð78S764Ł[

Cl3CO OCCl3

OCO2H

NH2

OHO

NH

CO2H

O

+ 1/3

1 mol l–1 NaOH

dioxan(85)

Cl3CO OCCl3

O

+THF, RT, 30 min

75% N

OMeO

H

O

MeO OH

NH2

(86)1/3

5[04[2[0[6 N!Carboxy a!amino acid anhydrides

N!Carboxy a!amino acid anhydrides "NCAs#\ or Leuchs anhydrides ð95CB746\ 63HOU"04:1#076Ł\constitute a special category of mixed anhydrides which achieve both amino group protection andcarboxylate activation of a!amino acids simultaneously[ The apparent advantage of the concurrentamine protection and carboxylate activation in NCAs is\ however\ counterbalanced by their highreactivity[ These reagents are sensitive to moisture and are prone to polymerization[ NCAs can beprepared by a facile one!pot reaction at room temperature[ In a typical reaction a N!t!BOC!aminoacid and triphosgene are stirred in ethyl acetate at room temperature[ Triethylamine addition to thesolution is accompanied by an instantaneous precipitation of triethylammonium chloride to a}ordan intermediate\ which reacts with the loss of carbon dioxide within 1Ð19 h depending on the aminoacid to give the desired product[ By this method the NCA of glycine is obtained in a yield of 72)"Scheme 12# ð81JOC1644Ł[

Cl3CO OCCl3

O

ButO NH

OO O

O Cl

ButO NH

O

OH

O

O

HN

O

OEt3N

+ CO2 + ButCl

Scheme 23

Daly and co!workers describe a preparative route which also uses triphosgene[ Treatment of asuspension of L!phenylalanine in anhydrous tetrahydrofuran with 0:2 equivalent of triphosgene at39Ð49>C leads to a completely homogeneous solution a}ording L!phenylalanine NCA within 2 h ina yield of 72) "Equation "76## ð77TL4748Ł[

Cl3CO OCCl3

O

+50 °C, THF

(87)OH

O

NH2 HNO

O

O

1/3

5[04[2[0[7 Urethanes as protection for amino functions

To establish chemoselectivity it is often necessary to block amino functions\ particularly in peptideand nucleotide chemistry\ by reversibly protecting them\ mainly by protective groups of the urethanetype[ These can easily be introduced as well as cleaved by standard methods ð63HOU"04:0#35\ B!71MI

376One Chalco`en

504!91Ł[ Usually benzyloxycarbonyl! "Z!# ð21CB0081Ł\ t!butoxycarbonyl! "t!BOC!# ð46JA5079Ł\ and~uorenylmethoxycarbonyl! "FMOC!# ð69JA4637Ł residues are applied[ In some cases\ increasedselectivity combined with particularly mild reaction conditions is achieved by special methods[Examples include reagents with b!haloalkyl groups ð65AG"E#570\ 68LA167Ł particularly the 1\1\1!trichloro!t!butoxycarbonyl! "TCBOC!# residue ð67AG"E#250Ł[

A comprehensive survey of carbamate protection of amino functions is available ðB!80MI 504!92Ł[The following examples illustrate recent uses of carbamate protection in synthesis[

In a synthetic approach to the alkaloid lycorine the amino function of an intermediate is protectedby an ethoxycarbonyl residue\ which is introduced by ethyl chloroformate in the presence oftriethylamine ð89H"29#728Ł[

Water!soluble analogues of the important antitumor alkaloid camptothecin have been developedby SmithKline Beecham Pharmaceuticals[ The amino group in a polyfunctional intermediate isprotected by the Z!residue\ introduced with benzyl chloroformate\ as shown in Equation "77#ð80JMC87Ł[

NO2

O

NMe

H*HCl

Z–Cl

CH2Cl2, Et3N, 0 °C

NO2

O

NMe

Z(88)

The problem of guanidino function protection has been taken up by Dodd and Kozikowski inthe conversion of alcohols to guanidines[ The latter are blocked by Z! or t!BOC!groups[ Thus N\N?!bis"benzyloxycarbonyl#guanidine or N\N?!bis"t!butoxycarbonyl#guanidine react as nucleophiles inthe Mitsunobu protocol with several di}erent alcohols according to Equation "78#\ a}ording thecorresponding alkylguanidine in excellent yields\ in most cases more than 84) ð83TL866Ł[

(89)

R1 = t-BOC or Z

R1N N

R1

H

NH2

R2 R3

HO H+

dead

PPh3R2 R3

H N

R1

N

NH2

R1

As part of a total synthesis of thymosin b3\ an optimized conventional synthesis of the C!terminaltridecapeptide fragment "20Ð32# is described by Link and Voelter ð82ZN"B#0999Ł[ The N!terminal a!amino group is protected by Z! and the o!amino functions of lysines by t!BOC!residues\ as shownin the following sequence "20Ð32# of thyrosin b3] Z!Lys"t!BOC#!Glu"O!But#!Thr"But#!Ile!Glu"O!But#!Gln!Glu"O!But#!Lys"t!BOC#!Gln!Ala!Gly!Glu"O!But#!Ser"But#!OBut[

t!BOC!Group protection is also useful in an e.cient procedure for the synthesis of phos!phoropeptides by the t!BOC mode solid phase method[ A phosphothreonine!containing peptiderelated to the EGF receptor protein was synthesized by this methodology ð82CL0390Ł[

For alkylating both ends of tetraamines\ reversible masking of all amino groups is necessary andcan be performed by reaction with t!BOC!O!t!BOC ð80JMC458Ł[

Previously described protecting groups\ Z\ BOC\ and FMOC residues are also used in thepharmaceutical and other industries as amino function blocking groups\ as shown in some patentsfrom the 0889s ð82EUP459629\ 82EUP436588\ 82MIP8294915Ł[

An e.cient Leu!enkephalin synthesis using highly lipophilic ferrocenylmethyl "Fem#\ t!BOC\ andTCBOC residues has been performed by Eckert et al[ ð80ZN"B#228Ł[ Introduction of the TCBOC!residue into the building block H!Fem!Gly!OMe is carried out with 1\1\1!trichloro!t!butyl chloro!formate\ yielding 62) product\ as shown in Equation "89#[ The chloroformate TCBOC!Cl is easilyobtained by reaction of 1\1\1!trichloro!t!butanol with triphosgene\ as described by the same authorð76AG"E#783Ł[

Fe

N

TCBOC

OMe

O

Fe

N

H

OMe

O

+ TCBOC-Clpyridine

(90)

TCBOC = Cl3CCMe2OCO


The extremely selective and mild cleavage of b!haloalkoxycarbonyl groups makes them excep!tionally useful in semisyntheses of highly sensitive penicillin and cephalosporin derivatives\ asrecently demonstrated by Eckert ð89ZN"B#0604Ł[ Introduction of the 1\1!dibromopropoxycarbonylgroup by means of its chloroformate at D!phenylglycine produces 89) of the urethane[

The TCBOC!residue is also suitable for amino function protection in nucleotide chemistry[ Ugiand co!workers prepared all possible N!protected nucleosides with TCBOC!residue\ as exempli_edby the nucleic acid bases N!TCBOC!adenine "02# and N!TCBOC!uracil "03# ð72T1196\ 74ACS"B#650Ł[A di!TCBOC!adenine derivative is also described by Ugi in the direct synthesis of cyclic AMPderivatives ð82ACS014Ł[

N

NN

N

HN O

OCCl3

(13)

N

N

O

(14)

O

OCCl3

O

An example of another special protective group for amino function protection is the 1!trimethyl!silylethoxycarbonyl residue TMS!CH1CH1OCO "TEOC#[ It proved useful in the key step of a highlystereoselective three component coupling in the _rst total synthesis of the antitumor antibiotic "¦#!hitachimycin[ The urethane intermediate is obtained by reaction with the corresponding chloro!formate in excellent yield\ according to Equation "80# ð81JA7997Ł[

SS

HN

PMB

Ph

H

O-PMB

SS

TEOCN

PMB

Ph

H

O-PMB

TEOCCl

K2CO3, THF99%

(91)

TEOC = 2-trimethylsilylethoxycarbonylPMB = p-methoxybenzyl

5[04[2[0[8 Polyurethanes

Polyurethanes are an important class of polymers ðB!78MI 504!90Ł[ They are produced by poly!addition of diisocyanates with diols[ Typical representative monomers are hexamethylene!0\5!diisocyanate\ phenylene!0\3!diisocyanate\ diphenylmethane!3\3?!diisocyanate\ and naphthalene!0\4!diisocyanate as the isocyanate component and 0\3!butanediol\ 0\3!bis"2!hydroxypropyl#benzene\0\3!bis"1!hydroxyethoxy#benzene\ 1\1!bisð3!"1!hydroxyethoxy#phenylŁpropane as the diol com!ponent[ Patent literature in this _eld provides information on advances ð81GEP3104537\ 81GEP3108307\81JAP94228115\ 81JAP94228431\ 81JAP95922997Ł[

5[04[2[0[09 Carbazates

Generally carbazates can be divided into two groups] monoacylated and bisacylated derivatives[They are obtained simply by reacting alkyl or aryl chloroformates with hydrazine hydrate\ or withalkyl! or arylhydrazine derivatives[ Monocarbazates are formed exclusively by carrying out theabove reactions in organic solvents such as chloroform or acetone under ice cooling ð72HOU"E3#162\80TL09942\ 82JA7787Ł "Equation "81##[

NH

NH2

Ph

O

O

Cl

Ph

O

O + H2N–NH2•H2OCHCl3

(92)

378One Chalco`en

Instead of chloroformates\ unsymmetrically substituted O!alkyl O?!phenyl carbonates can beused^ the phenoxy group activates the carbonate ester ð57HCA511\ 73CJC463Ł Equation "82##[

Dpoc–ODpoc

NH

NH2H2NNH2

O

ODpoc =

(93)

Another method for preparing monoacylated carbazates makes use of dialkyl dicarbonates^ thus\0!ethoxycarbonyl!0!methylhydrazine is formed by reacting methylhydrazine and diethyl carbonateð72HOU"E3#163Ł "Equation "83##[

N NH2

OEt

O– CO2–EtOH Me

OEt

O

O

OEt

O

MeNH

NH2(94)+

Bisacylated hydrazines\ particularly the symmetrical ones\ are obtained very easily by reactingchloroformates and hydrazine hydrate in aqueous solution ð55CB1928\ 72HOU"E3#168Ł[

In aqueous solution dialkyl dicarbonates also react with hydrazine hydrate to give N\N?!bis!"alkoxycarbonyl#hydrazines[ Also\ mixed anhydrides prepared from potassium alcoholate\carbon dioxide\ and dialkyl chlorophosphate react with hydrazine to give bisacylated hydrazinesð72HOU"E3#168Ł[

An acylated carbazate derivative is generated in the reaction of a diaziridinone with the sodiumsalt of malonitrile in addition to a pyrazoline and a tetraazaspirononane derivative ð81JOC6248Ł[

5[04[2[0[00 Azidoformates

Azidoformate esters\ N2CO1R\ can be prepared by either of the following general routes] "0# thediazotization of the corresponding carbazates NH1NHCO1R^ "1# the reaction of chloroformatesClCO1R with sodium azide or a similar reagent ð72HOU"E3#173Ł[ The chloroformate can be generatedin situ from an alcohol and phosgene^ this is illustrated by the conversion of a 06!hydroxysteroid intothe corresponding chloroformate "Equation "84## ð80JCS"P0#26Ł[ Alkylcarbonic diethylphosphoricanhydrides\ RCOCO1P"O#"OEt#1\ have been used as alternatives to chloroformates^ for example\a convenient preparation of t!butyl azidoformate\ BOC!N2\ is the reaction of t!butylcarbonicdiethylphosphoric anhydride with potassium azide ð77OSC"5#196Ł[

O N3

O

MeO

OH

COCl2

NaN3

(95)

5[04[2[1 Oxygen and Phosphorus Functions

The main interest in phosphoryl O!alkyl carbonates is based on the potential biological activityof these phosphorus compounds ð77JMC0720\ 89BBR"060#347\ 82MI 504!92Ł[ In particular\ AZT phos!phonates have been investigated as possible prodrugs in HIV!research ð89BBR"061#177\ 80MI 504!91\82MI 504!91Ł[

5[04[2[1[0 Phosphinecarboxylates from alkali metal phosphides and carbon dioxide

Kuchen and co!workers have prepared the lithium and sodium salts of diphenylphos!phinecarboxylic acid from the easily available lithium and sodium diphenylphosphides and carbondioxide ð80PS"59#176\ 82PS"72#54Ł "Equation "85##[


Ph2PM + CO2

Ph2P O– M+

O

M = Na, Li

(96)

These compounds rapidly decompose in protic media\ undergoing decarboxylation and formationof diphenylphosphine[ Treatment of the phosphinecarboxylates with TMS!Cl leads to the trimethyl!silyl ester\ and with dimethyl sulfate to the methyl ester\ whereas reaction with alkyl iodides gaveonly the dialkyldiphenylphosphine with liberation of carbon dioxide "Scheme 13#[

Ph2P O– M+

O (MeO)2SO2

Ph2P OMe

O

Ph2P O-TMS

O

Ph2PH

H2O

Ph2PR

–CO2 RI

TMS-Cl

Scheme 24

Bubner and Balszuweit synthesized methyl di!n!butoxyphosphinecarboxylate oxide\ "BUO#1P"O#CO1Me\ in a similar way starting from sodium di!n!butyl phosphite ð76ZAAC"435#031Ł[

5[04[2[1[1 Phosphinecarboxylates by the Arbuzov reaction and related methods

Reaction of alkyl chloroformates with monoalkylphosphines a}ords monoalkylphos!phinecarboxylates^ for example\ phenyl phenylphosphinecarboxylate is obtained in 77) yieldð70ZN"B#809Ł "Equation "86##[

PhO Cl

O K2CO3

88%

P OPh

O

H

PhPH

H

Ph+ + HCl (97)

Alkyl dialkoxyphosphinecarboxylate oxides are prepared by reacting alkyl chloroformates andtrialkyl phosphites in a typical Arbuzov reaction ð89BBR"060#177Ł "Equation "87##[ If alkoxy"methyl#phosphinecarboxylate oxides are desired\ they can easily be prepared from dialkoxyphos!phinecarboxylates by addition of methyl iodide ð77PS"24#218Ł "Scheme 14#[

RO Cl

O+ (RO)3P RO P

O

O

OR

OR(98)

O

P OMeRO

OR

O

P OMeRO

MeRO

+I–

MeI

– RI

O

P OMeRO

OMe

Scheme 25

Similarly\ Prishchenko and co!workers have used methyl chloroformate instead of methyl iodideto obtain the phosphinedicarboxylate ð76JGU0373\ 76JGU0159\ 77PS"24#218Ł "Equation "88##[

O

(EtO)2P OMe+

O

Cl OMe

O

P OMe

O

MeO

OOEt

(99)

380One Chalco`en

Iyer et al[ produced bis"trimethylsilyloxy#phosphinecarboxylates by treatment of tris"trimethyl!silyl# phosphite with alkyl chloroformates ð78TL6030Ł "Scheme 15#[ In the same way\ alkyl"trimethyl!silyl#phosphinecarboxylates are prepared by the use of alkylbis"trimethylsiloxy#phosphinesð75ZAAC"431#26Ł[ A great variety of silylated phosphinecarboxylates have been prepared by Issleibet al[ ð74ZAAC"429#05Ł[ These silylated compounds are suitable for further derivatization[

R = Me, Et, Ph, 2,4-Cl2C6H3

P

O

TMS-OOR

OTMS-OOH

P

O

HOH

P O-TMS

TMS-O

TMS-OTMS-Cl ClCO2R

Scheme 26

Acylation of the silylated phosphinosaccharide shown in Equation "099# by benzyl chloroformateis the best method for introducing the carboxylate function at phosphorus ð78CAR"083#198Ł[

P

O

O

O

OO

O-TMS

ClCO2Bn

P

O

O

O

OO

O

OBn

O (100)

5[04[2[2 Oxygen and Other Heteroatom Functions

5[04[2[2[0 Oxygen and boron functions

Trimethylamine!carboxyborane is obtained by activating the cyano group in trimethylamine!cyanoborane by ethylation with triethyloxonium tetra~uoroborate\ followed by hydrolysis of theresulting nitrilium salt with water "Scheme 16#[

Me3NBH2CN + Et3O+ BF4–

CH2Cl2

∆Me3NBH2CNEt+ BF4

– + Et2O2 H2O

Me3NBH2CO2H + EtNH3+ BF4

–

Scheme 27

Similar amine!carboxyboranes are obtained by the same route ð68JINC0112\ 73IC2952\ 73IC3211\77JOM"233#18\ 78IS"14#68\ 89IC443Ł[

Esteri_cation of the alkylamine!carboxyboranes can be performed in di}erent ways[ Reactingtrimethylamine!carboxyborane with methanol using dcc as coupling reagent yields 71) of thecorresponding methyl ester ð75S722\ 78IS68Ł "Equation "090##[

BH2

OMe

O

Me3NBH2

OH

O

Me3N + MeOHdcc, CH2Cl2

RT, 1 week(101)

dcc = dicyclohexylcarbodiimide

To obtain the esters in good yields\ alkylamine!carboxyboranes can be treated with the cor!responding chloroformate of the alcohol[ For example\ trimethylamine!carboxy borane methylester is obtained "73)# by reacting trimethylamine!carboxyborane and methyl chloroformate withtriethylamine ð78IS"14#68Ł "Equation "091##[

Cl OMe

O

Me3NBH2CO2H + + Et3NCH2Cl2

cat., 0 °CMe3NBH2CO2Me + Et3N•HCl + CO2 (102)

The ester can also be prepared by reacting trimethylamine!carboxyborane with trimethyl ortho!formate in the presence of boron tri~uoride etherate ð81S279Ł "Equation "092##[ Another route


also starting with trimethylamine!carboxyborane uses N\N?!carbonyldiimidazole as the activatingreagent to obtain trimethylamine!imidazole!carbonylborane\ which then reacts with sodium ethox!ide to give the corresponding ethyl ester in a yield of 31) ð74ZN"C#233Ł[

BH2

OMe

O

Me3NBH2

OH

O

Me3N + HC(OMe)3

Et2O•BF3

98%(103)

A method that di}ers from the previously described routes has been developed by Miller\ whohas successfully synthesized the 1!carboxylic acid derivative of 0\0\3\3!tetramethyl!0\3!diazonia!1\4!diboratacyclohexane ð80IC1117Ł "Scheme 17#[

Me2N

H2B NMe2

BC + Me3N•BH2N

Me2N

H2B NMe2

B

H

NBH2NMe3+ I–

H

I

Me2N

H2B NMe2

B

H O

NH2

+ 2H2 + Me3N + B(OH)4– 0.15 mol l–1 H+

Me2N

H2B NMe2

B

H

CO2H

0.5 mol l–1 NaOH

Scheme 28

Alkylphosphine!carboxyboranes can be obtained in a similar manner[ Triphenylphosphine!car!boxyborane and tricyclohexylphosphine!carboxyborane both are obtained by reacting the cor!responding cyanoborate with triethyloxonium tetra~uoroborate followed by hydrolysis with waterto yield the products in 29) and 64) yields\ respectively ð70JINC346\ 81AP"214#156Ł "Equation "093##[

(104)BH2

OH

O

R3PBH2

CNR3P i, EtO3+ BF4

–

ii, H2O

R = Ph, cyclohexyl

Triethyl phosphite!carboxyborane is obtained by a di}erent hydrolysis procedure starting fromtriethyl phosphite!cyanoborane as outlined in Scheme 18 ð80T5804Ł[

BH2

NH

O

(EtO)3P i, EtO3

+ BF4–

ii, NaOH (aq.)BH2

CN(EtO)3PEt

3 mol l–1 HCl

BH2

OH

O

(EtO)3P

Scheme 29

5[04[2[3 Sulfur and Nitrogen Functions

5[04[2[3[0 Thiocarbamates from chlorothioformates and amines

The synthesis and use of disubstituted thiocarbamates has been well!documented in the literatureðB!69MI 504!90\ B!66MI 504!90\ B!71MI 504!90Ł[

Simple thiocarbamates\ such as N\S!diethyl thiocarbamate and S!ethyl N!phenyl thiocarbamate\are readily obtained from the reaction of the appropriate amine with ethyl chlorothioformate"Equation "094## ð74JOC4768Ł[

(105)NH

SEt

O

RCl SEt

OR–NH2 +

382One Chalco`en

5[04[2[3[1 Thiocarbamates from carbamoyl chlorides and thiols

Another method is based on the treatment of thiols with carbamoyl chlorides in the presence ofbases or alkali metal thiolates[ In an example reported in 0878\ Threadgill and Gledhill convertedN!t!BOC!cysteine methyl ester into the S!"N\N!dimethylcarbamoyl#cysteine derivative in excellentyield by reaction with dimethylcarbamoyl chloride and pyridine "Equation "095## ð78JOC1839Ł[

(106)Cl NMe2

O

t-BOC-NH CO2Me

SH

+

t-BOC-NH CO2Me

S

OMe2N

pyridine

96%

A special synthesis starting from dialkylcarbamoyl chlorides and episul_des in equimolar amountsat 099Ð019>C in the presence of triethylamine or pyridine as catalyst leads to S!1!chloroalkyl N\N!dialkyl thiocarbamates "in analogy to similar epoxide reactions# in yields of 49Ð79) ð57ZOR0550Ł"Equation "096##[

S

R1N S

O

R2

R2

R1

Cl

N Cl

O

R2

R2

+ (107)

D|Amico and Schafer reported an alternative synthesis of disubstituted thiocarbamates by usingpotassium alkyl or benzyl dithiocarbonates ð79PS"7#290Ł[ Treatment of these dithiocarbonates withdisubstituted carbamoyl chlorides a}ords disubstituted thiocarbamates "Scheme 29#[

N Cl

O

R2

R3R1O S– K+

S

R3N S OR1

R2

O O

R3N SR1

O

R2

R3N OR1

S

R2

+(A)

(B)

–COS

Scheme 30

R1 = Me, Et, Bu

In all probability a mixed anhydride is formed but immediately decomposes to give carbonylsul_de and the disubstituted thiocarbamate "A#[ The proposed nucleophilic displacement mechanismis depicted in Scheme 20[

S–N

O

Me

Me

SR1N

O

Me

Me

S

S OR1

N

O

Me

Me

S–N

O

Me

MeS

S OR1

N

O

Me

Me

+

–COS –COS

Nu

S–R1O

SNu =

+ R1Nu

Scheme 31


5[04[2[3[2 Thiocarbamates from isocyanates and thiols

A widely used route to thiocarbamates is the reaction of isocyanates with thiols "Equation "097##[In comparison with alcohols\ thiols are less reactive[ Thus the use of higher temperatures or ofcatalysts such as triethylamine ð46JA255Ł\ dabco\ diacetoxydibutyl stannate ð68GEP1810029Ł\ or tritonB "benzyltrimethylammonium hydroxide# ð79AP"202#884\ 70AP"203#204Ł is necessary[

N SR1

O

R2

HN C O

R2

+ HS–R1 (108)

Threadgill and Gledhill synthesized S!"N!alkylcarbamoyl# derivatives of cysteine\ cysteinylglycineand glutathione by this route ð78JOC1839Ł[ Thus N!t!BOC!cysteine methyl ester was carbamoylatedsmoothly using the appropriate isocyanate in dichloromethane "Equation "098##[

N C O

R

t-BOC-NH CO2Me

S NHR

Ot-BOC-NH CO2Me

SH

(109)+

Cysteinylglycine and glutathione derivatives were prepared in the same way[ Many of the depro!tected S!carbamoylamino acids and peptides are metabolites of the corresponding N!alkyl!for!mamides in rodents and in humans[

5[04[2[3[3 Thiocarbamates from 0!chlorothioformimidates

Hydrolysis of chlorothioformimidates is another way of preparing thiocarbamates ð55AG109Ł"Equation "009##[ The methods of preparation of the precursors are described in Section 5[19[0[2[1[

In an anhydrous medium these alkylimino chloromethyl sul_des give\ after addition of carboxylicacid and base\ N!acylated thiocarbamates "Scheme 21# ð71JCS"P0#1702Ł[ These are formed by acylmigration from oxygen to nitrogen[

NH

S

O

RCl

PhN S

Cl

RCl

Ph (110)

R = –(CH2)– , Pr

NaOH (aq.)

,

O R3

ONR1

R2SR3 N SR2

R1

O O

R1N

Cl

SR2

R3CO2H

base

Scheme 32

5[04[2[3[4 Thiocarbamates from alkylamide salts\ carbon monoxide\ and sulfur

An e.cient synthesis of S!alkyl thiocarbamates was developed by Mizuno et al[ ð80TL5756Ł[ Thekey step of this synthetic method is conversion of a carbamoyllithium species\ generated from alithium dialkylamide and carbon monoxide\ into the lithium thiocarbamate by addition of elementalsulfur[ In the subsequent step\ S!alkylation with alkyl halides a}ords various S!alkyl thiocarbamatesin yields of 44Ð88)[ The reaction provides a useful method for the synthesis of S!alkyl thio!

384One Chalco`en

carbamates because of the mild reaction conditions\ good yields and easy availability of the reagents"Scheme 22#[

R1R2NH + BuLiTHF

–78 °C to –20 °CR1R2NLi

CO (1atm)

–78 °C, 1 h

O

N SR3R1

R2

O

N S– Li+R1

R2

O

NR1

R2

– Li+S8

–78 °C to 0 °C

R3X

Scheme 33

In an earlier work\ Mizuno prepared ammonium thiocarbamates in the presence of selenium ascatalyst to obtain S!alkyl thio!carbamates ð78AG"E#341Ł[

The use of selenium as a catalyst for the synthesis of S!alkyl thiocarbamates was described byKoch ð64TL1976Ł\ who treated primary amines with disul_des and carbon monoxide in the presenceof selenium "Equation "000##[ The conditions required are mild and aromatic amines can be usedprovided that triethylamine is added as a cocatalyst[ In the catalyzed system a selenocarbamateintermediate may be involved similarly to the method described by Mizuno and co!workers "Equa!tion "001## ð78AG"E#341Ł[

O

N SR2R1

H

Se+ HSR2SS

R2

R2

R1–NH2 + + CO (111)

O

N SR2R1

H

+ R2S– + SeSS

R2

R2

+

O

N Se–R1

H

(112)

5[04[2[3[5 Thiocarbamates by ð2\2Ł!sigmatropic rearrangement

Various thiocarbamates were prepared by Koch[ An elegant path to S!aryl thiocarbamates isthe thermal rearrangement "NewmanÐKwast rearrangement# of O!aryl thiocarbamates "Equation"002##[

N S

O

R

R

ArN O

S

R

R

Ar ∆(113)

This reaction is formulated as an intramolecular four!membered ring process ð60BCJ0282Ł\ whereasthermal treatment of O!allyl thiocarbamates to S!allylthiocarbamates is described as a ð2\2Ł!sig!matropic rearrangement "Equation "003## ð68CL0250Ł[

∆

O

SR3

NMe

Me

R2

R1 R1 O

S

R2 NMe

Me

R3

(114)

The thiocarbamates are derived from allylic alcohols after treatment with sodium hydride andN\N!dimethylthiocarbamoyl chloride[ The distillation of this mixture provides the requisite allylicthiocarbamate[ The thiocarbamates have been used by Mimura and co!workers as key intermediatesfor the stereoselective synthesis of trisubstituted alkenes and of various types of a\b!unsaturatedcarbonyl compounds ð68CL0250Ł[

For the synthesis of N\N!disubstituted thiocarbamates it is also possible to use COS addition tosecondary amines and alkyl halides in aqueous sodium hydroxide "Equation "004##ð79PS"7#290Ł[ This


method requires the reaction to be carried out at low temperatures "9Ð09>C#[ An excess "29Ð39)#of the secondary amine must be employed in order to minimize the hydrolysis of carbonyl sul_deto carbon dioxide and hydrogen sul_de[

R2S N

O

R1

R1

N H + COS + NaOH + R2X

R1

R1

+ NaX + H2O (115)

5[04[2[3[6 Thiocarbamates from 1!dialkyliminium!0\2!oxothiolane iodides

When working with 1!alkylimino!0\2!oxathiolanes\ Hoppe and Follmann discovered a newmethod for the preparation of S!vinyl thiocarbamates ð66AG"E#351Ł[ By elimination of HI from 1!dialkyliminium!0\2!oxathiolane iodides\ S!vinyl thiocarbamates are formed "Scheme 23#[

OSS

R2

NMe2

O

R3

R2

NMe Me

R1R3

R2

+

–HI

MeIOS

NMe

R1R3

R2

I–

Scheme 34

5[04[2[3[7 Thiocarbamates as amine protective groups

The thiol!labile dithiasuccinoyl "Dts# Na!amino protecting group and N!thiocarboxy anhydridesof a!amino acids are reported to have certain advantages for peptide synthesis ð57JA2143Ł[ Theseamino function protecting groups are available from the appropriate ethoxythiocarbonyl derivativesof amino acids "Scheme 24#[ A convenient procedure for the synthesis of ethoxythiocarbonylderivatives was developed by Barany ð67JOC1829Ł[

Scheme 35

EtO NS

SN

O

O

R1

O

Y1 S

H

R1

Y1

OS

N

H

O

R1

O

Y1 = –OH, –OR2, –NHCH(R3)COY2

5[04[2[3[8 Thiocarbamates by other methods

Akiba and Inamoto developed a synthesis of S!alkyl thiocarbamates in which the conversion ofan imino group into a carbonyl group is achieved via a nitrosimine ð62CC02Ł[ A mixture of the S!alkylisothiourea or its hydrobromide and isopentyl nitrite in benzene was heated at 49Ð59>C toobtain the S!alkyl thiocarbamate in good yield "Scheme 25#[

+

R1S NR2R3

NH2Br–

R1S NR2R3

NNO

R1S NR2R3

O–N2Pri

ONO

Scheme 36

R1 = Bn, Et; R2 = Me, Et, Ph; R3 = Ph

386One Chalco`en

The synthesis of rather exotic thiocarbamates is described by Schroll and Barany ð75JOC0755Ł[The reaction of alkoxydichloromethyl chlorocarbonyl disul_des with an excess of N!methylanilineleads to the postulated key intermediate "A# in Scheme 26\ which o}ers three pathways to di}erentthiocarbamates[

S N

O

Me

Ph

SN

O

Me

Ph

S N

O

Me

Ph

SCl

ORCl

(A)

S N

O

Me

Ph

NMe

Ph

S Cl

O

SCl

ORCl

S N

O

Me

Ph

SRO

O

excess PhNHMe

Scheme 37

5[04[2[4 Sulfur and Phosphorus Functions

It is known that O!alkylthiocarbonyl compounds undergo alkyl migration from oxygen to sulfur[The ethyl ester of dibutylphosphonous acid reacts with alkyl chlorothioformates to yield phosphinylalkylthioformates "Equation "005##[ The reaction of the components is accompanied by a thioneÐthiol rearrangement which occurs at 09Ð24>C^ thus\ the expected phosphinyl thionoformates arenot obtained[ Two mechanisms of the rearrangement are possible at the stage of formation of theintermediate product of the Arbuzov reaction[ In the _rst case\ a four!centered cyclic transitionstate is formed\ similar to that in the thioneÐthiol rearrangement[ In a second variant the authorspropose that the phosphorus atom becomes pentavalent\ forming a P0S bond in a three!memberedring[ Stabilization is due to the transfer of the alkyl cation to the sulfur atom ð77ZOB15Ł[

Bun2P SMe

O

OMeO Cl

SBun

2POEt + + EtCl (116)

Analogous compounds from the patent literature are important as plant growth regulators\ andare obtained from trialkyl phosphites and chlorothioformates ð63USP2738091\ 64GEP1324396Ł[

5[04[2[5 Other Mixed Systems

5[04[2[5[0 Selenium and nitrogen functions

Selenocarbamates can be obtained as described by Kondo and co!workers by reaction of anamine\ carbon monoxide\ and elemental selenium\ followed by treatment with an alkyl halide\ ingood to excellent yields ð78AG"E#341Ł[ Se!n!Butyl N\N!diethyl selenocarbamate is prepared quan!titatively by this procedure using n!butyl iodide "Equation "006##[


Et2N SeBun

O

Et2NH + Se

i, CO (1 atm)ii, BunI, THF

(117)

A di}erent route to the same selenocarbamate uses N\N!diethylcarbamoyl chloride and lithiumn!butylselenide ð68S486Ł "Equation "007##[

Et2N SeBun

O

BunSeLi + + LiCl65%Et2N Cl

O(118)

3!Methyl!1!phenyl!0\1\3!selenadiazolidine!2\4!dione is obtained by pyrolyzing 1!methyl!3!phenylallophanoyl selenocyanate with elimination of HCN ð71TL1722Ł "Equation "008##[

N N

O

Se

O

CN

Me

Ph

H N Se

NO

Me

O

Ph

–HCN

∆(119)

5[04[2[5[1 Tellurium and nitrogen functions

A tellurocarbamate\ Te!butyl N\N!diethyl tellurocarbamate is synthesized by reacting metallictellurium with n!butyllithium at 9>C and further reaction with diethylcarbamoylchloride "Scheme27# ð89SC692Ł[

Et2N TeBun

OEt2N Cl, 25 °C

O

Te + BunLi0 °C, THF

BunTeLi

Scheme 38

Another convenient method to obtain unsymmetrical tellurocarbamates uses bis"N\N!dimethyl!carbamoyl# ditelluride\ which is prepared in 47) yield by treating DMF with sodium metal andelemental tellurium under argon ð74CL0560Ł[ Reduction of this reagent by sodium borohydride andfurther reaction of the resulting monotelluride with n!hexyl iodide a}ords Te!n!hexyl N\N!dimethyltellurocarbamate in an excellent yield of 81) "Equation "019## ð81CL0278Ł[

(120)Me2N TeC6H13

O

Me2N Te

O

Te NMe2

O

i, ii

i, NaBH4 (2.2 equiv.), Et2O, –50 °C; ii, n-C6H13I, EtOH, reflux


6.16Functions Containing aCarbonyl Group and TwoHeteroatoms Other Than aHalogen or ChalcogenANTHONY F. HEGARTY and LEO J. DRENNANUniversity College Dublin, Republic of Ireland

5[05[0 FUNCTIONS CONTAINING AT LEAST ONE NITROGEN FUNCTION "AND NOHALOGENS OR CHALCOGENS# 499

5[05[0[0 Carbonyl Derivatives with Two Nitroèn Functions 4995[05[0[0[0 Acyclic ureas 4995[05[0[0[1 Cyclic ureas 4955[05[0[0[2 Carbamoyl azides 400

5[05[0[1 Carbonyl Derivatives with One Nitroèn and One P\ As\ Sb or Bi Function 4005[05[0[1[0 Carbonyl derivatives with one nitroèn and one phosphorus"III# function 4005[05[0[1[1 Carbonyl derivatives with one nitroèn and one phosphorus"V# function 4015[05[0[1[2 Carbonyl derivatives with one nitroèn and one arsenic function "carbamoylarsines# 4025[05[0[1[3 Carbonyl derivatives with one nitroèn and one antimony function 4025[05[0[1[4 Carbonyl derivatives with one nitroèn and one bismuth function 402

5[05[0[2 Carbonyl Derivatives with One Nitroèn and One Metalloid "B\ Si\ Ge# Function 4035[05[0[2[0 Carbonyl derivatives with one nitroèn and one boron function 4035[05[0[2[1 Carbonyl derivatives with one nitroèn and one silicon function "carbamoylsilanes# 4045[05[0[2[2 Carbonyl derivatives with one nitroèn and one èrmanium function "carbamoylèrmanes# 404

5[05[0[3 Carbonyl Derivatives with One Nitroèn and One Metal Function 4055[05[0[3[0 Carbon monoxide insertion reactions 4055[05[0[3[1 Nucleophilic attack on metal carbonyl complexes 4065[05[0[3[2 Other methods 406

5[05[1 FUNCTIONS CONTAINING AT LEAST ONE PHOSPHORUS\ ARSENIC\ ANTIMONYOR BISMUTH FUNCTION "AND NO HALOGEN\ CHALCOGEN OR NITROGENFUNCTIONS# 406

5[05[1[0 Carbonyl Derivatives with Two P\ As\ Sb or Bi Functions 4065[05[1[1 Carbonyl Derivatives with One P\ As\ Sb or Bi Function Toèther with a Metalloid or

Metal Function 408

5[05[2 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION"AND NO HALOGEN\ CHALCOGEN OR GROUP 4 ELEMENT FUNCTIONS# 408

5[05[2[0 Carbonyl Derivatives with Two Silicon Functions 4085[05[2[1 Carbonyl Derivatives with Two Boron Functions 4195[05[2[2 Other Carbonyl Derivatives with Two Dissimilar Metalloid Functions 4195[05[2[3 Carbonyl Derivatives with One Metalloid and One Metal Function 419

5[05[3 CARBONYL DERIVATIVES CONTAINING TWO METAL FUNCTIONS 410

5[05[3[0 Metal Carbonyl Complexes and Fluxionality 410

388

499 Carbonyl and Two Heteroatoms Other Than a Haloèn or Chalcoèn

5[05[3[1 Preparation of Metal Carbonyls 4115[05[3[1[0 Metal carbonyls of titanium\ zirconium and hafnium 4115[05[3[1[1 Metal carbonyls of vanadium\ niobium and tantalum 4115[05[3[1[2 Metal carbonyls of chromium\ molybdenum and tun`sten 4115[05[3[1[3 Metal carbonyls of manànese\ technetium and rhenium 4125[05[3[1[4 Metal carbonyls of iron\ ruthenium and osmium 4125[05[3[1[5 Metal carbonyls of cobalt\ rhodium and iridium 4135[05[3[1[6 Metal carbonyls of nickel\ palladium and platinum 4145[05[3[1[7 Metal carbonyls of copper\ silver and òld 4145[05[3[1[8 Mixed metal carbonyls 414

5[05[0 FUNCTIONS CONTAINING AT LEAST ONE NITROGEN FUNCTION "AND NOHALOGENS OR CHALCOGENS#

5[05[0[0 Carbonyl Derivatives with Two Nitrogen Functions

5[05[0[0[0 Acyclic ureas

"i# Synthesis of urea

Urea "2#\ the parent compound of carbonyl derivatives with two nitrogen functions\ may beprepared by the action of ammonia "0# on hydrogen isocyanate "1# "Equation "0## or by usingammonia instead of a substituted amine in the reactions outlined in the subsequent sectionsð72HOU"E3#223Ł[ Urea is an important starting material for the synthesis of substituted ureas[ As aweak base it can be used as a catalyst in chemical reactions[

(1)NH3 + O C NHO

H2N NH2

(1) (2) (3)

"ii# Reaction of amines:imines with phosène

Phosgene "3# may be attacked by amines or imines to yield N!alkylated symmetrical ureas\ in allcases[ Primary amines require temperatures ×099>C to form substituted ureas successfully^ attemperatures ³099>C the isocyanate may be formed[ Equation "1# outlines the reaction of asecondary amine "4# with phosgene "3# to give the N\N\N ?\N ?!tetrasubstituted urea "5#[ The reactiontakes place in inert solvents and the generated hydrogen chloride reacts with excess amine[ Thisequation applies equally for primary amines[ For R0�1!nitrophenyl\ R1�H a yield of 70) hasbeen reported ð46JGU1489\ 46JGU1771\ 71JPR116Ł[ For tertiary amines "6# the reaction involves the lossof an alkyl chloride rather than hydrogen chloride[ Benzyl chloride is lost more easily than alkylchloride but aryl chlorides are more di.cult to remove "Equation "2### ð23BSF133\ 35MI 505!90\ B!60MI505!90\ 62OSC"4#190\ 70JOC2900Ł[ Imines "8# react similarly "Equation "3##\ usually involving the loss ofhydrogen chloride\ which can be reacted with excess imine or an added tertiary amine "e[g[\ pyridine#ð68JPR716Ł[

O

Cl Cl

(4)

+ R1

N NR2

O

R2 R1

(6)

NR1 R2

(5)

H –2[R1R2NH2]+Cl–

toluene, 100 °C, 35 min(2)

O

Cl Cl

(4)

+ 2R3N

(8)

R2N NR2

(7)

O–2RCl(3)

490At Least One Nitro`en

O

Cl Cl

(4)

+ 2 N N

O

(10)

R1 R2

(9)

NH CHCl3, pyridine

–2HCl(4)R2

R1

R2

R1

"iii# Reaction of amines with S!chlorothiocarbonyl chloride

The reaction of 0H!benzotriazole "01# with S!chlorothiocarbonyl chloride "00# in dichloromethaneat 19>C for 2 h results in the formation of 0!"0H!benzotriazolocarbonylthio#!0H!benzotriazole "02#which\ on heating at 29>C\ yields 0\0?!carbonyl!bisbenzotriazole "03# "51)# with loss of sulfur"Scheme 0# ð68LA0645Ł[

O

Cl SCl

NN

N

H

O

SN

N NN

NN

O

NNNN

NEt3, CH2Cl2

–2HCl

(12)(11)

+ 2

N N

(13) (14)

∆

–S

Scheme 1

"iv# Reaction of amines with carbamic acid chlorides

This synthesis allows the possibility of forming unsymmetrical ureas[ Again the reaction involvesthe formation of hydrogen chloride which may be precipitated as an amine hydrochloride salt eitherby using an excess of base or by adding a tertiary amine "Equation "4## ð25JCS0162\ 56JMC430\ 69JOC732\61GEP1195255\ 71JOU0847Ł[ For R0�Et\ R1�Ph\ R2�H\ R3�H the reaction involves the bubblingof ammonia gas "05# "R2�R3�H# through a solution of N!ethyl!N!phenylcarbamic acid chloride"04# and results in the precipitation of ammonium chloride and ½099) yield of the urea "06#ð25JCS0162Ł[ The major drawback of this method is that compound "04# is carcinogenic\ so othersynthetic pathways should be employed if possible[

O

Cl N

(15)

R3

N NR1

O

R4 R2

+ NR3 R4

(17)

H

(16)

base, 2:1 C6H6:EtOH

–HClR1

R2

(5)

"v# Reaction of amines with carbamic acid esters

The sodium methoxide!catalysed reaction of amines "08# with carbamic acid esters "07# at 054>Cresults in the formation of N!substituted ureas[ For R0�Et\ R1�Ph\ R2�H\ R3�Bu\ R4�Buthe product N\N!dibutyl!N?!phenylurea has been isolated in 84) yield "Equation "5## ð57T1256\61CL860Ł[ This method works well if the ester group is a good leaving group such as phenoxy\


3!nitrophenoxy or 1\3\4!trichlorophenoxy[ Both symmetrical and unsymmetrical ureas can be syn!thesized by this method[

O

O NR2

N NR5

O

R3 R4

(18)

NR4 R5+

H

(20)(19)

R3

R2

dioxane, NaOMe, 165 °C

–R1OH

R1(6)

"vi# Reaction of amines with carbonic acid esters

High temperatures and pressures must be used to e}ect the reaction of diphenyl carbonate "10#with dimethylamine "11#\ but the yield of N\N\N?\N?!tetramethylurea "12# is 62) "Equation "6##ð52AG0948\ 55JMC333\ 62GEP1130360\ 67JHC0120Ł[

O

O O Me2N NMe2

O

Ph Ph

H

NMe Me

(21)

+

(23)(22)

200 °C, ~200 atm., 4 h

73%(7)

"vii# Reaction of amines with 3\5!diphenylthienoð2\3!dŁ!0\2!dioxol!1!one 4\4!dioxide

The following is a general method for the preparation of tetrasubstituted symmetrical or unsym!metrical ureas in very high yields in which the leaving group can be recovered for re!use[ The cycliccarbonate "13# was reacted in THF with an equimolar quantity of amine "14# at 19>C for 29 min[Following addition of an equimolar quantity of the second amine "15# and re~ux for 19 min\ thetetrasubstituted urea "16# was isolated in overall 68Ð87) yield "Scheme 1# ð68CB616Ł[

SO2

O

OO

Ph

Ph

SO2

Ph

Ph

HO

O

O

N

N

R3

R4

R2

R1

+SO2

O

NR1 O

O

R2

Ph

Ph

(24) (27)

NHR1R2

(25)

THF, 20 °C

NHR3R4

(26)

reflux79–98%

Scheme 2

"viii# Reaction of amines with urea

This is a general method for the synthesis of N!mono! or N\N!disubstituted ureas[ Alkylamines"18# or hydrochloride salts of alkylamines "29# react with urea "17# in a replacement reactioninvolving the loss of ammonia or ammonium halide and yielding the required substituted urea"20# in high yield "Equation "7##[ The N\N!disubstituted urea contaminant can be removed byrecrystallization[ The above reaction using cyclohexylamine yields N!cyclohexylurea in 85) yieldð72GEP2024000Ł[

(28)

+ RNH2 (or +NRH3 X–)O

H2N NH2

(30)(29)

O

RHN NH2

–NH3

(or NH4X)(8)

(31)

"ix# Oxidation of thioureas

Thioureas "21# may be oxidized to the corresponding ureas "22# by a variety of reagents] manga!nese dioxide in dichloromethane ð67BCJ0134Ł\ t!butyl hypochlorite in carbon tetrachloride ð72T0618Ł\


sodium nitrite in 3 mol l−0 hydrochloric acid ð71T0052Ł\ or mercuric acetate in dichloromethane"Equation "8## ð89JHC1104\ 80TL3680Ł[

R1

N NR4

O

R2 R3

(33)

oxidation(9)R1

N NR4

S

R2 R3

(32)

"x# Addition to isoureas

Isoureas "23# may be cleaved by the addition of HX "where X�OH\ OR\ NHR# in a nucleophilicfashion to yield substituted ureas "24# as shown "Equation "09## ð63YGK825\ 70ACH46Ł[

O

N NMe2

O

X

O

N

H

NMe2

O

(34) (35)

+HX(10)

X = OH, OR, NHR

"xi# Preparation from ortho!carbonic acid derivatives

The hydrolysis of bis"dialkylamino#dichloromethanes "25# results in the isolation of ureas "26#"Scheme 2# ð67IZV119Ł[

O

N NH

R

H

R

N NH

R

H

R

Cl Cl

CCl42RNH2, CuCl2

–2HCl

+H2O

–2HCl

(36) (37)

Scheme 3

"xii# Addition of amines to carbon oxide sul_de

This is a two!step reaction which is carried out in inert solvents such as benzene\ toluene\methanol\ propanol or butanol and involves an intermediate which need not be puri_ed before thesubsequent reaction[ N\N!Dimethyl!N?!phenylurea "31# was prepared by the action of dimethyl!amine "28# on carbon oxide sul_de "27# in toluene and the subsequent reaction of aniline "30# withthe intermediate "39# formed[ The temperature was maintained at 19>C for 44 min then brought to71>C over 09 min before maintaining it at 71Ð78>C for 3 h to e}ect complete reaction[ The isolatedyield was 70) "Scheme 3# ð68GEP1631047Ł[

Scheme 4

(38) (39)

O

Me2N NHPh

(40) (41)

O

Me2N S–

+NH2Me2CO S + 2HNMe2

PhNH2

(41)

[Me2NH2] HS–+


"xiii# Addition of amines\ imines or water to isocyanates or alkali metal cyanates

For this reaction\ increasing the electron!withdrawing power on the isocyanate results in anincrease in the reactivity towards the nucleophile[ N?!Cyclohexyl!N!ð"1!methoxycarbonyl#phenylŁurea "34# can be prepared by the reaction of equimolar amounts of the methyl ester of 1!amino!benzoic acid "33# and cyclohexyl isocyanate "32# at re~ux for 19 min in petroleum ether "b[p[ 89Ð099>C# using a catalytic amount of triethylamine[ The isolated yield was 83) "Equation "00##ð50JOC4127Ł[ This reaction type is known for a large variety of amines and isocyanates ð15JA0625\38JA1186\ 46JA4606\ 46LA"598#72\ 51JOC1511\ 52JMC558\ 68JMC17\ 68JOU0966\ 79JCED181\ 79JOC775\ 71CPB423\72CPB30\ 89H"20#0282\ 89JOC2588\ 80IZV1482\ 81S186Ł[

(11)NCO

N

H

N

O

H

CO2Me

H2N

O OMe

(45)

(44)(43)

+pet. ether (90–100)

reflux, 20 min94%

N\N?!Diphenyl!N!"0!phenyl!0!propenyl#urea "37# can be prepared by reacting equimolar amountsof propiophenone phenylimine "36# with phenyl isocyanate "35# for 1 h at ½029>C[ The reportedyield is 66) "Equation "01## ð79CB1388Ł[ This reaction is also generally applicable ð75CB1442Ł[ Thereaction of water with alkyl isocyanates "38# leads to the production of primary amines "49# whichthen react with excess alkyl isocyanate "38# in the usual way to form symmetrical disubstituted ureas"40# "Scheme 4#[ The yield of N\N?!didodecylurea made in this manner has been reported as 80)ð54MI 505!90Ł[

H

NCO

N

Ph

N

O

Ph

(48)(47)(46)

Ph+

Ph NPh

Et 130 °C, 2 h

77%(12)Ph

NCO

NHR

NHR

O

Scheme 5

(51)(49)

+H2O

–CO2

RH2NR

NCOR

(50)

Alkali metal cyanates "41# react with amines "42# to form ureas "43# "Equation "02##[ In thesynthesis of N!heptylurea\ heptylamine\ ice\ ice!water and 4 mol l−0 hydrochloric acid were heatedto 69Ð79>C before the sodium cyanate was added portionwise[ After 1Ð3 h two phases separatedwhich\ following isolation\ yielded 75Ð77) of the desired monosubstituted urea ð52OSC"3#404Ł[

NH2

NR1R2

O

(54)(53)

H2O

HCl+ Na+ – NCO

(52)

NH

R1

R2(13)

"xiv# Hydrolysis of cyanamides

Ureas "45# are also formed by the action of water on cyanamides "44# in a reaction which can becatalysed by either acids or bases "Equation "03## ð55CB1826\ 70GEP1744771Ł[ The cyanamides decom!


pose to the corresponding amides on heating to 064>C with concentrated hydrochloric acid[ Thebest yields are obtained by using basic hydrogen peroxide under mild conditions[

NH2

N

O

(56)

NC

H

R

(55)

H

R

H2ON (14)

"xv# Oxidative amination of carbon monoxide

Two equivalents of amine may attack carbon monoxide to form ureas "46#\ provided an oxidationprocess also occurs "Equation "04##[ In the synthesis of N\N?!bis"ethoxycarbonylmethyl#urea\ carbonmonoxide is bubbled through a solution of glycine ethyl ester\ triethylamine and catalytic seleniumin THF at 19>C for 3 h[ The isolated yield was 87) ð68S624Ł[

NHR

NHR

O2 RNH2 + CO + 1/2 O2

(57)

Se

–H2O(15)

"xvi# Reaction of amines with isocyanides

Ureas may also be synthesized in a redox reaction of mercuric salts "47# and amine "48# onisocyanide "59# "Equation "05##[ For example\ N!butyl!N?!"1\5!dimethylphenyl#urea "50# is preparedas shown in 77) yield ð61TL3152Ł[ The order of decreasing reactivity of the mercuric salts isHg"OCOMe2#1×Hg"NO2#1×HgCl1ŁHg"CN#1[

NH

O

BunHN

CN

(61)(60)

Hg(OCOMe)2 + 3BunNH2 +

(58) (59)

–Hg, –2MeCONHBun

88%(16)

"xvii# Hydroxyureas and alkoxyureas

This class of compounds may be synthesized by the reaction of phosgene with hydroxylaminehydrochloride ð55JCS"C#249Ł\ with N!hydroxylamines ð64CZ134Ł or with O!methylhydroxylaminehydrochloride ð55JCS"C#249Ł in dioxane:water in the presence of potassium acetate to yield thesymmetrical N\N?!dihydroxyurea or N\N?!dimethoxyurea[

Carbamic acid chlorides react with hydroxylamine in dioxane\ in the presence of triethylamine\to form the corresponding N\N!dialkyl!N?!hydroxyurea derivatives[ The yield of N\N!diethyl!N?!hydroxyurea prepared by this method is 57)\ while the reported yield of the N\N!dimethyl derivativeis 75) ð63AP"296#6Ł[

N!Hydroxyurea has been prepared by the reaction of ethyl carbamate "urethane# with hydroxyl!amine hydrochloride in alkaline solution at ½19>C with reported yields of 42Ð62) "Equation "06##ð62OSC"4#534Ł[

HON N

H

O

H H

+~20 °C

(17)EtO N

H

O

H

HN

OH

H

•HCl

The addition reaction of isocyanates or alkali metal cyanates with hydroxylamine or hydroxyl!amine derivatives in benzene\ THF\ diethyl ether or dichloromethane solution occurs at ½19>C[


For example\ equimolar amounts of O!phenylhydroxylamine and methyl isocyanate react at 19>Cover 0 h to yield 81) of the required N!methyl!N?!phenoxyurea "51# "Equation "07## ð72S360Ł[

ON N

Me

O

H H

(62)

20 °CH

N

H+ Ph (18)

OPh

CN

Me

O

"xviii# Acylureas

The N!acyl derivative of urea can be prepared by the synthesis of the O!acyl derivative followedby an internal O:N rearrangement of the acyl group ð68COC"1#0983Ł[ For example\ the O!acylderivative is formed in the reaction of acryloyl chloride and urea[ The O:N rearrangement occursin inert solvents such as dioxane\ THF or chloroform at 19Ð39>C in the presence of triethylamineor sodium carbonate to give N!acryloylurea in 42[4) yield ð57CB1308Ł[

The reaction of acetamide with half an equivalent of bromine in base gives an isocyanateintermediate which reacts further with acetamide to form N!acetyl!N?!methylurea in 79Ð73) yieldð32OSC"1#351Ł[

Other methods which may be employed in the synthesis of acylureas include the reaction ofphosgene with acylamines ðB!54MI 505!91Ł\ the reaction of N!acylcarbamidic acid esters with aminesðB!54MI 505!91Ł\ the hydrolysis of N!acylcyanamides ð57USP2428458\ 57USP2464864Ł\ the reaction ofisocyanides with N!bromosuccinimide or with N!bromoacetamide ð52BCJ0203Ł\ the hydrolysis ofN!"0!chloro!0!alkenyl#urea ð61AG882Ł\ the addition of carboxylic acids to carbodiimides ð54JOC1738\55JA0913\ 56CRV096Ł and the reaction of N!hydroxyformamides with acyl chlorides ð68CZ064Ł[

"xix# Nitrosoureas

The synthesis of nitrosoureas may be carried out\ in good yield\ by reacting an N!nitrosocarbamicacid ester with an amine under mild conditions ð71JMC067Ł[

N!Methyl!N!nitroso!N?!"1!phenylethyl#urea "52# has been prepared by the reaction of a solutionof N!methyl!N?!"1!phenylethyl#urea in formic acid and water with an aqueous solution of sodiumnitrite at 9Ð4>C over 29 min "Equation "08##[ The isolated yield of the N!nitrosourea derivative isreported as 73) ð52JMC558\ 55JA2687Ł[

MeN N

O

NO H

HCO2H, H2O, NaNO2

0–5 °C, 30 min(19)

(63)

PhMe

N N

O

H H

Ph

"xx# Azodicarbonyl amides "bis"aminocarbonyl#diazines#

Members of this class of compounds have been prepared by the oxidation of the correspondingN\N?!bis"aminocarbonyl#hydrazines or by the reaction of bis"alkoxycarbonyl#diazines with primaryor secondary aliphatic amines ð55AG265\ 71AHC"29#0Ł[ The latter has been used to produce N\N\N?\N?!tetramethylazodicarboxamide in 68) yield ð62JOC0541Ł[

5[05[0[0[1 Cyclic ureas

"i# Reaction of diamines with phos`ene

Cyclic ureas are the products in this and subsequent reactions[ Diamines "53# do not react withphosgene "56# to form the required cyclic urea "58# directly but need to be activated[ Therefore\ the


diamine "53# is treated with hexamethyldisilazane "HMDS# "54# under re~ux for 09 h to yield 77)"n�3# of the bis"trimethylsilylamino#alkane "55#[ The reaction of "55# with phosgene "56# occurs intoluene at 9>C in 0 h\ facilitated by triethylamine[ For n�2\ the yield is 59)^ for n�3\ the yield is64)[ The 0\2!bis"trimethylsilyl#!1!oxo product "57# is readily hydrolysed in ½099) yield to formthe cyclic urea product "58# "Scheme 5# ð59CB1709\ 64JCS"P0#101\ 66AJC344Ł[ Polymeric ureas may beformed even if the reaction mixture is very dilute[

N

NO

H

H

N

NO

TMS

TMS

NTMS

H

N

H

TMS

( )n

(69)

TMSN

TMS

( )n

(68)

H

H2O, EtOH

100%

COCl2 (67), NEt3toluene, 0 °C, 1 h

( )n

(66)

H2N

H2N

(65)( )n

reflux, 10 h89%

(64)

Scheme 6

"ii# Reaction of imines with chloroformate esters

The one!step synthesis of 1!oxo!0\2\3\4!tetraarylimidazolidine "61# has been reported via thereaction of two equivalents of arylaldehyde arylimine "69# with sodium in ether "2 h re~ux# followedby the addition of ethyl chloroformate "60# to the _ltrate of the _ltered initial reaction mixture and0 h re~ux "Equation "19##[ The reaction yields 59) of a racemic mixture of d! and l! products and17) of the meso!compound[ The diastereomers can be separated by recrystallization ð69JOC1988\60JOC1405\ 79IJC"B#542\ 79S0990Ł[

N

NO

Ar2

Ar2

Ar1

Ar1

+N

NO

Ar2

Ar2

Ar1

Ar1

meso (72) d-, l-

NAr1

Ar2

(70)

i, Na, Et2O, reflux, 3 h

ii, ClCO2Et (71), reflux, 1 h2 (20)

"iii# Reaction of diamines with dialkyl carbonates

This reaction usually requires vigorous conditions but the reaction of 0\1!diaminoethane "63#with bis"succinimido#carbonate "62# occurs readily at 19>C in good yield "89)# to form 1!oxoimi!dazolidine "64# "Equation "10## ð71SC102Ł[

(21)+ NHO

O

O

(75)(74)

20 °C

90%

N

NO

H

H

H2N

H2N

O

O

O

N

N

O

O

O

O

+

(73)

"iv# Pyrolysis of bis"carboxyalkylamino#alkanes

An excellent yield "½099)# has been reported for the thermal conversion of 0\3!bis"carboxy!alkylamino#alkanes "65# into 0\2!dimethyl!1!oxoimidazolidine "66# "Equation "11## ð68AG"E#492Ł[


(22)

(77)(76)

pyrolysis, 350 °C, 20 torr

–K2CO3100%

N

NO

Me

Me

N

N

CO2– K+

Me

CO2– K+

Me

"v# Reaction of urea with aldehydes and ketones

The condensation of aldehydes and ketones with urea can lead to a large variety of mono! andpolycyclic ureas[ Cyclic ureas such as 2\6!dioxo!1\3\5\7!tetraazabicycloð2[2[9Łoctane "79# may besynthesized by the reaction of two equivalents of urea "67# with aldehydes such as glyoxal "68#"Equation "12## ð0766LA"078#048\ 41USP1481454Ł[

(23)

(80)(78)

H2O, H2SO4

70 °C, 1 h88%

N

NO

H

H

N

NO

H

H

+2 O

NH2

NH2

O

O

(79)

"vi# Cyclization of N!"v!haloalkyl#ureas

Ureas may be cyclized readily if there is a suitable leaving group on the N!alkyl chain[ Thesynthesis of 0\2!diphenyl!1!oxoimidazolidine "71# "R0�R1�Ph\ R2�R3�H# was carried out byreacting 09 mol l−0 sodium hydroxide in ethanol for 04 min at re~ux with 0!"1!chloroethyl#!0\2!diphenylurea "70# "R0�R1�Ph\ R2�R3�H#[ The yield was reported as 35) "Equation "13##ð62JHC528Ł[ This procedure is generally applicable for various R groups\ leading to a wide varietyof cyclic ureas "71# ð40JOC0718\ 42CJC785\ 42JA0019\ 54CJC0687\ 69JOC732\ 60JHC446\ 68JOU0966Ł[

N

NO

R2

R1

R3

R4

(24)N

N H

R3

R4

R2

O

R1

Cl

(82)(81)

NaOH, EtOH, reflux, 1.5 min

–HCl

"vii# Addition of diamines to alkali metal cyanates

Diamines "72# add to alkali metal cyanates "73# to yield cyclic ureas "74# "Equation "14##ð55JMC741Ł[ The reaction gives yields of 21Ð77) for various R groups "R�H\ Me\ CF2\ SMe\ Cl\Br# and is again applicable to other similar systems ð34JA1968\ 36JA2049\ 46JA4609\ 62JMC890Ł[

R

NH

H2N

(83)

R

N

N

O

H

i KOCN (84), H+

ii, 215–225 °C

(85)

(25)


"viii# Cyclization of N!"1!propynyl#ureas

N!"1!Propynyl#ureas "75# are cyclized in good yield at mild temperatures by the action of base toform cyclic ureas "76# "Equation "15## ð51JOC2968\ 52JOC880\ 53JOC0740\ 67JOC50Ł[

N

NO

R4

R1

(26)HN

N

R4

O

R1

(87)(86)

NaOEt, 20 °C, 1 h

80–90%R3

R2

R2

R3

"ix# Cyclization of N!haloureas

2!Membered ring cyclic ureas can be synthesized in good yield from N!haloureas[ The cyclizationis carried out by potassium in pentane or by potassium t!butoxide in t!butanol[ For example\ thereaction of bis"t!butyl#urea "77# in t!butanol with t!butyl hypochlorite yields the N!halourea "78#\which may then be cyclized by the addition of potassium t!butoxide to form the cyclic urea "89# inan overall 89) yield "Scheme 6# ð58JOC1143Ł[ This reaction also works for other N!substituted ureasð58JOC1152\ 61LA"654#83\ 67JOC811Ł[

HN

N H

But

O

But

(88)

ButOH, ButOCl

10 min

ClN

N H

But

O

But

(89)

ButO– K+

10 minO

N

N

But

But

(90)

Scheme 7

"x# Oxidation of cyclic thioureas

Cyclic thioureas "80# can be oxidized to the corresponding cyclic ureas "81# by the action of arange of oxidizing agents such as potassium permanganate ð66BSB552Ł\ hydrogen peroxide ð45CB232\47JA5398\ 70JMC0978Ł or dimethyl selenoxide ð67JOC1021Ł "Equation "16##[

oxidationS

N

N

(91)

O

N

N

(92)

(27)

"xi# Addition of diamines to carbon oxide sul_de

The synthesis of 1!oxo!perhydropyrimidine "84# involves the reaction of 0\2!diaminopropane "82#and carbon oxide sul_de in 49) ethanol at 56>C for 19 min followed by the addition of HCl andheating at 73>C for 0[4 h[ The isolated yield of "84# was 70) ð68USP3043820Ł[ The reaction goesthrough an intermediate "83# "Scheme 7#[


H2N NH2

(93)

COS

N

N

H

H

OH

H3N

N

O–S

+

–H2S

(94) (95)

Scheme 8

"xii# Reaction of isocyanates and aziridines

The reaction of isocyanates "85# with aziridines "86# proceeds smoothly at 099>C in the presenceof lithium halides to yield cyclic ureas "87#[ For R0�benzoyl and R1�1!phenylethyl the yield of0!benzoyl!1!oxo!2!"1!phenylethyl#imidazolidine "87# has been reported as 48) "Equation "17##ð55LA"587#079Ł[ Alkyl and aryl isocyanates also trimerize in a competing reaction[

N

NO

R1

R2

(28)

(98)(97)

LiX

100 °C, 1–3 hN R2

N C O

R1

(96)

+

X = Cl, Br

"xiii# Reaction of carbodiimides and oxiranes

This reaction is catalysed by alkali metal hydroxides\ tertiary amines or lithium chloride[ A cyclicurea "090# has been synthesized in the reaction of phenyl oxirane "099# with diphenylcarbodiimide"88# at 199>C under nitrogen for 6 h and in the presence of lithium chloride[ The reported yield was82) "Equation "18## ð50CB2176Ł[

(29)N

NO

Ph

Ph

(101)(100)

LiCl, N2

200 °C, 7 h

OPhN C N

Ph

(99)

+

Ph

Ph

"xiv# Reaction of diamines with carbon monoxide

The reaction of diamines "092# with carbon monoxide "091# takes place using various conditions\depending on the chain length\ to yield the cyclic ureas "093#[ Either sulfur in methanol or seleniumin THF can be used for the reaction and the conditions vary from 39Ð019>C\ and from 3Ð49 atmpressure to give yields of 47Ð87) "Equation "29## ð60JA5233Ł[

(30)58–98%

(103)

O

N

H

N

H

(104)

H2N

CO +

(102)

H2N

"xv# Rin` expansion of cyclic amidoximes

The synthesis of 1!oxo!0\2!diazacyclododecane "095^ x�6# is carried out by Beckmann rearrange!ment on 1!hydroximinoazacycloundecane "094^ x�6# in phosphoric acid for 09 min at 019>C\ then


49 min at 039Ð049>C[ The reported yield of the cyclic urea "095# was 65) "Equation "20##ð46LA"596#56\ 67JOC0433Ł[ This is a very good method for preparing cyclic ureas containing largerings[

N

N

N

NHO

H

O

H

H

( )x ( )x

H3PO4, 120–150 °C

76%

(105) (106)

(31)

5[05[0[0[2 Carbamoyl azides

Carbamoyl azides\ R0R1NCON2\ are most generally prepared by one of two routes[ The _rst ofthese is the displacement of chloride from the corresponding carbamoyl chloride\ R0R1NCOCl\ byreaction with sodium azide ð69JHC796Ł[ The second general route involves the diazotization of thehydrazides R0R1NCONHNH1 ð75T1566Ł[ The second method was used to prepare the highlyunstable and explosive carbonic diazide\ CO"N2#1\ ð0784JPR"1#361Ł which has subsequently beenshown to react with benzene to give N!"azidocarbonyl#azepine ð55CI"L#0155Ł[

Carbamoyl azides RNHCON2 can also be prepared directly from aldehydes RCHO by oxidationwith pyridinium chlorochromate "pcc# in the presence of sodium azide[ This method probablyinvolves the intermediacy of an acyl azide which undergoes Curtius rearrangement and furtherreaction with sodium azide ð77SC434Ł[

5[05[0[1 Carbonyl Derivatives with One Nitrogen and One P\ As\ Sb or Bi Function

5[05[0[1[0 Carbonyl derivatives with one nitrogen and one phosphorus"III# function

The synthesis of carbonyl derivatives with one nitrogen and one phosphorus function\ thephosphorus being a secondary phosphine "098#\ is achieved by reacting a phosphine "096# with anisocyanate "097# "Equation "21##[ The reaction has been carried out with R0�R2�phenyl andR1�"CH1#nSH "n�1\ 2# at room temperature and resulted in an isolated yield of 51Ð64)ð62JPR360Ł[ The same reaction with R0�Ph or cyclohexyl\ R1�CHPhCH1COR3 "R3�Me\ Ph\But#\ R2�Ph carried out in ethanol or acetone as solvents gave "098# in yields of 45Ð66) ð69JPR255Ł[

P NR3

O

R2 H

(109)

+ (32)CN

R3

OR1

HP

R2

R1

(107) (108)

Tris"trimethylsilyl#phosphane "009# and isopropyl isocyanate "000#\ when stirred in diethyletherfor 2 days\ react to form a compound of the required type "001b#[ However\ compound "001b# isunstable and reacts further to form compounds with phosphorusÐcarbon triple bonds "Scheme 8#ð78AG"E#42Ł[

N CPri

O(TMS)2P

O-TMS

N Pri

(TMS)2P

O

N Pri

TMS

C compoundsPP(TMS)3 + 87%

(110) (111) (112a) (112b)

Scheme 9

In an unusual reaction\ it has been reported that phosphiatriafulvene "002# and isocyanates "003#"R�Me\ Ph# react in diethylether over 5 h to form imidoesters "005# and amides "006# via a betaine


intermediate "004# "Scheme 09# ð80S0988Ł[ If the phosphine does not have a hydrogen substituent\the product of addition to isocyanates may be formed in very good yield and may also be stableð66CB1257Ł[

But

But

P

TMS

O

N

R+

But

But

P

N

OBut

But

P

–+

N

TMS-OTMS

R

R

(113)

+Et2O, 6 h

–78–20 °C

–

(115)(114)

(116)(117)

But

But

P

TMSN C O

R

Scheme 10

5[05[0[1[1 Carbonyl derivatives with one nitrogen and one phosphorus"V# function

These compounds "019# are formed when a phosphine oxide "007# reacts with an isocyanate "008#"Equation "22##[ This has been achieved with R0�R1�OMe and R2�SO1NCO[ The reaction inether at 9>C gave the required product "019#[ However\ if the reaction is carried out at 19>C for0 h a 1 ] 0 product is formed "i[e[\ ð"MeO#1P"O#NHŁ1SO1#[ This reaction is generally applicable andalso works for R0�R1�Et\ Pr\ Pri\ Bu and Bui ð57USP2390103\ 58RZC0332\ 62JGU0908Ł[ The reactionhas also been carried out with R0�R1�OMe and R2�Ts in benzene under re~ux for 4 h[ Therequired product "019# was isolated[ The same authors have synthesized several other compounds"019# bearing a variety of arenesulfonyl groups ð57USP2302271Ł[

N C O

R3

(119)

O

PR1 H

R2

P

O

R2N

O

R3

HR1

+

(118) (120)

(33)

The synthesis of compounds "013# has also been achieved by reacting compounds of type "TMS!O#PH"OR0# "010# with OCNCH1CO1R1 "011# in ether at ¾24>C for 0 h to give "012# in quantitativeyield^ these reacted with aqueous sodium hydroxide at −4>C to give the desired products "013#"Scheme 00# ð76EGP131701Ł[ This method is applicable for R0�H\ TMS\ alkali metal and "sub!stituted# ammonium and R1�H\ alkyl and an alkali metal[

O

PR1O

N

O

H

CO2R2

(124)

H

PTMS-O

N

O

H

CO2R2

O C N

O

OR2 R1O

PTMS-O OR1

H

(121)(122) (123)

Et2O

100%

NaOH (aq.)

–5 °C+

Scheme 11

The synthesis of phosphine oxides "016# can be achieved by the reaction of the phosphonate esters"014# with amines "015# "Equation "23## ð68EUP2997Ł[ For R0�R1�Et\ R2�R3�H\ R4�Me the


reaction involves the passing of ammonia into the reaction mixture at 39>C for 2 h to yield therequired product "016#[ A similar reaction with R0�R1�R4�Me and 0\0\2\2!tetramethylguanidineas the amine "015# gave "MeO#1P"O#CON1C"NMe1#1 as the product ð65GEP1442036Ł[

P

O

R2ON

O

R4

R1O

(126)

+

R3

P

O

R2ON

O

R5

R1O

N

H

R3 R4

(125) (127)

(34)

R5

The reaction of trialkyl phosphite "017# and alkyl chloroformate "018# at 014>C yields thephosphonate "029#\ which with ammonia\ or other amines\ gives the required carbamoyl phos!phonates "020# "Scheme 01#[ This method works for R0\ R1�alkyl\ allyl\ haloalkyl\ alkoxyalkyl andalkenyl^ R2�Me^ R3�Me and R4�alkyl\ alkynyl and hydroxyalkyl ð60GEP1939256\ 63USP2738091\66GEP1527643Ł[ In an Arbuzov reaction\ trimethyl phosphite "022# has been incorporated into com!pound "021# to form "023# in 87) yield at 19Ð29>C "Equation "24## ð71EUP32867Ł[

(129)

OR2

PR1O OR3

P

O

R2OO

O

R4

R1O+

(128) (130)

125 °CO

Cl OR4 P

O

R2ONH2

O

R1O

Scheme 12

(131)

NH3

P

O

MeON

O

MeO

(134)

(35)

Me

O

O

O

O

O

N

O

MeO

Cl

(MeO)3P (133)

20–30 °C98%

(132)

5[05[0[1[2 Carbonyl derivatives with one nitrogen and one arsenic function "carbamoylarsines#

The synthesis of carbamoylarsines "026# has been carried out by one of two methods^ the reactionof alkyl or aryl arsines "024# with phenyl isocyanate "025# in the presence of dibutyltinacetate toform N!phenylcarbamoyl arsines "Equation "25##\ or the reaction of lithium arsides "027# withcyclohexyl isocyanate "028# to form N!cyclohexylcarbamoyl arsines "039# "Scheme 02#[ The formerreaction does not work for cyclohexyl isocyanate ð56LA"698#137Ł[

RnAsH3–n + (3–n)N C

Ph

ORnAs

O

NHPh 3–n

Bu2Sn(OAc)2, dioxanereflux, 5 h

60–89%

(36)

(135) (136) (137)

R = Ph, n = 2; c-C6H11, n = 2; Ph, c-C6H11; Ph, n = 1; Bu, n = 1

5[05[0[1[3 Carbonyl derivatives with one nitrogen and one antimony function

No compounds of this type were found in the literature[

5[05[0[1[4 Carbonyl derivatives with one nitrogen and one bismuth function

The synthesis of compounds of this type was achieved by Mishra and Tandon _rst by forminga 0 ] 0 adduct of DMF "030# with bismuth trichloride "031# and then by reacting this with bases to


N C

c-C6H11

O

O

NLi3–nAsRn + (3–n) RnAs c-C6H11

(138) (139)

LiOEt + RnAs

O

N

Li+

–

3–n

(140)

c-C6H11

Scheme 13

H

3–n

H2O EtOH

41–71%

Et2O

RT

R = Ph, n = 2; c-C6H11, n = 2; Bu, n = 1

form the isolated compounds such as "032#[ The bases used were triethylamine\ diethylamine\ a!picoline and pyridine[ Scheme 03 gives an outline of the mechanism when pyridine is used ð60IC0785Ł[

MeN

O

MeN+

N BiCl

NMe2

O

Cl–

(141)

+ BiCl3 BiCl3•HCONMe2

(142) (143)

Scheme 14

5[05[0[2 Carbonyl Derivatives with One Nitrogen and One Metalloid "B\ Si\ Ge# Function

5[05[0[2[0 Carbonyl derivatives with one nitrogen and one boron function

Compounds of this type have been synthesized in many di}erent ways^ the reaction of H!Ala!OMe =HCl in dichloromethane with triethylamine\ Me2N =BH1CO1H and dicyclohexylcarbodiimide"dcc# gives L!Me2N =BH1CONHCHMeCO1H ð78EUP225661Ł[ Dipeptide and tripeptide esters cansimilarly be used ð89EJM290Ł[ Boron analogues of hydroxamic acids can be made by reactinghydroxylamine hydrochloride with Me2N =BH1CO1H in water to give an 74) yield of Me2N =BH1C"O#NHOH =HCl ð77IC291Ł^ Me2N =BH1CO1H reacts with R0R1NH in the presence of dcc inchloroform at room temperature to give Me2N =BH1CONR0R1 ð89BCJ2547Ł^ cyclic examples maybe synthesized "e[g[\ a carbamoyl analogue "033# of the cyanoborane oligomer "BH1CN#x# by putting"EtO#1P"O#CH1NMe1 =BH1CONHEt on silica gel ð80IC1322Ł[ The reaction of phenylaniline methylester hydrochloride with trimethylamine!carboxyborane\ triphenylphosphine\ carbon tetrachlorideand triethylamine in acetonitrile for 13 h yields Me2N =BH1CO!Ph!OMe ð81MI 505!90Ł[

N

BN

BH

Et

HH

H

Et

H H

O

O

(144)

A common way of making these compounds is exempli_ed by that reported by Sood et al[\ whichinvolved the reaction of cyanoborane "034# with triethyl phosphite "035# to form the triethylphos!phite!cyanoborane adduct "036# followed by ethylation with triethyloxonium tetra~uoroborate to


form the nitrilium ion "037#[ This was readily hydrolysed to triethyl phosphite!N!ethyl!carbamoylborane "038# "Scheme 04# ð80T5804Ł[ Many other papers make use of the same methodon di}erent substrates ð65JA4691\ 68JINC0112\ 70JINC346\ 78CC899\ 89IC443\ 89IC2107\ 80IC0935\ 81IC3800Ł[

(EtO)3P•BH2CNEt –BF4+

(148)

O

(EtO)3P•BH2 NHEt

Et3O+ BF4–, CH2Cl2

reflux, 48 h

(EtO)3P (146), DME

RT, 4 dor reflux, 2 d

58%(147)

(149)

1 mol l–1 NaOH to pH 11

73%

(BH2CN)x

(145)

(EtO)3P•BH2CN

Scheme 15

5[05[0[2[1 Carbonyl derivatives with one nitrogen and one silicon function "carbamoylsilanes#

Carbamoylsilanes may be made by the addition of hexamethyldisilathiane "040# to N\N!diethyl!carbamoylmercury "049# in ether[ The product\ N\N!diethylcarbamoylsilane "041#\ however\ candecarbonylate "Equation "26## ð58CC351Ł[

Hg(CONEt2)2 + (TMS)2S TMS-CONEt2Et2O

(150) (151) (152)

(37)

Hydrosilylation of alkyl isocyanates with triethylsilane in the presence of palladized charcoal orpalladium dichloride at 79Ð029>C for 5 h yields 39Ð89) of the desired product "RNHCOSiEt2#ð66JOM"039#86Ł[ Deoxygenation of cyclohexyl isocyanate with Ph1"Me2C#Si−Li¦ in an NMR tubeat −49>C in THF resulted in the identi_cation and isolation of N!cyclohexyl!t!butyldiphenyl!silylcarboxamide "042# ð72T1878Ł[ A solution of "TMS#2SiLi"THF#2 in pentaneÐTHF "09 ] 0# addedover 1 h to a solution of Me1NCOCl in dry pentane under dry nitrogen at −29>C then stirred atroom temperature yields 64) of "TMS#2SiCONMe1 ð80JOM"392#182Ł[

Ph2(But)SiCONH

(153)

5[05[0[2[2 Carbonyl derivatives with one nitrogen and one germanium function "carbamoylgermanes#

Carbamoylgermanes may be synthesized by treating lithium t!butylamide "043# with carbonmonoxide "044# to form "t!butylcarbamoyl#lithium "045#\ which reacts with trimethylgermyl chloride"046# to form the required product "047# "Scheme 05#[ Yields are in the region of 44) ð60AG"E#228Ł[

ButN GeMe3

H

O

ButN Li

H

O

ButN Li

H

ButN

Li

H

+ COC6H6, Et2O

50 °C ..

Me3GeCl (157)

–LiCl

(158)(156)(154) (155)

Scheme 16

Another method for the preparation of carbamoylgermanes is the reaction of triethyl!germyllithium "048# with amides "059# in hexane at −29>C for 4 h followed by hydrolysis[ For


R�Me\ the yield of N\N!dimethylamidetriethylgermylcarbonyl acid "050# is 34) "Equation "27##ð73IZV0786Ł[

R = Me, Et

TMS CONR2 TMSEt3GeLi + Et3GeCONR2 +

(159) (160) (161)

(38)

5[05[0[3 Carbonyl Derivatives with One Nitrogen and One Metal Function

5[05[0[3[0 Carbon monoxide insertion reactions

The insertion of carbon monoxide into a previously formed metalÐnitrogen bond is the most!studied method of synthesizing this type of compound ð76OM261\ 77AOC"17#028\ 77CRV0948\78CCR0Ł[ The _rst example of carbon monoxide insertion into a d! or f!element metal to di!alkylamide bond giving rise to carbamoyl insertion products was reported by Fagan ð70JA1195Ł[The facile insertion of carbon monoxide into chlorobis"pentamethylcyclopentadienyl#uranium andthorium dialkylamido complexes "051# led to the formation of the h1!carbamoyl complexes Mðh!Me4C4Ł1ðh1!CONR1ŁCl "052# "Equation "28##[ Bis"dialkylamido# compounds "053# are more reactivetoward carbon monoxide than the chloro analogues "051# "Scheme 06#[ The yield of bis"car!bamoyl#Mðh!Me4C4Ł1ðh1!CONR1Ł1 "055# is ½29)\ but when the solutions are maintained undervacuum at 099>C\ carbon monoxide loss occurs and the bis"carbamoyl# products "055# revert to themono insertion products Mðh!Me4C4Ł1ðh1!CONR1ŁNR1 "054#[

NR2

MCp* Cp*

Cl

+ CO MCp* Cp*

Cl

R2N O

(162) (163)

toluene95–100 °C

1 atm, 1.5–2.0 h55%

(39)

M = Th, U; R = Me, Et

NR2

MCp* NR2

Cp*

+ CO MNR2Cp*

Cp*

NR2O

(164) (165)

toluene

0 °C, 2 h40%

MCp*

Cp*

NR2O

(166)

NR2

O

Scheme 17

M = Th, U; R = Me, Et

65 °C, 1 atm CO, 1.5 h

vacuum, 100 °C

"dppe#PtMeðN"CH1Ph#"H#Ł "056# reacts with 2 atm of carbon monoxide at 14>C to give"dppe#PtMe"CONHCH1Ph# "057# in 79) yield "Equation "39## ð74OM828Ł[ Similarly\ the reactionof "dppe#PtMeNMe1 "generated in situ# with carbon monoxide leads to "dppe#PtMe"CONMe1# in65) isolated yield[

N

O

Pt

Me

(DPPE) Bn

H

(168)

N Bn

H

Pt

Me

(DPPE)

(167)

3 atm CO, 25 °C

80%(40)

Metals in groups 7\ 8 and 09 bearing amide ligands are not well known[ Cowan and Trogler havereported the carbon monoxide insertion reaction into the platinumÐamide bond of Pt"Ph1PCH1

CH1PPh1#"Me#ðNH"CH1Ph#Ł to generate the carbamoyl metal complex Pt"Ph1PCH1CH1PPh1#"Me#ðCONH"CH1Ph#Ł ð76OM1340Ł[ Carbon monoxide can also be inserted into the rutheniumÐamide bond[ When carbon monoxide is bubbled through a solution of h4!CpRu"NH1#"Cy1PCH1

CH1PCy1# "Cy�cyclohexyl#\ the carbamoyl complex h4!CpRu"CONH1#"Cy1PCH1CH1PCy1# is iso!lated ð80OM1670Ł[ An unusual reaction has been reported involving the insertion of carbon monoxideinto the iridiumÐnitrogen bond of Ir"CO#"NHAr#"PPh2#1 "058# "where Ar�Ph\ p!C5H3Me# at

406At Least One Phosphorus etc[

room temperature producing a 89) yield of the carbamoylÐmetal complex "069# "Equation "30##ð82OM1390Ł[

N

IrPh3P CO

PPh3

Ar HIr

Ph3PH

OC

Ph3P

R

N

O H

(169) (170)

CO (1 equiv.), RT

90%(41)

5[05[0[3[1 Nucleophilic attack on metal carbonyl complexes

CarbamoylÐmetal complexes can also be made by nucleophilic attack on metal carbonyls[ Thedirect addition of a nucleophilic nitrogen anion "Nu−# to a coordinated carbon monoxide ligand"M�Fe\ Ru\ Os\ Co\ Re\ Mo\ W# leads to the required compounds ð68JA0516\ 71IC0693\ 73JA0014\74JA1244\ 74M0092\ 74OM367\ 74OM0412\ 75JOM"201#C10\ 76IC415Ł[ The attack of the conjugate acid of anitrogen nucleophile "NuH# on metal carbonyls "M�Pt\ Ni\ Ir\ Fe\ Ru\ Os\ Mn# also results in thepreparation of carbamoylÐmetal complexes[ This method is restricted to strongly activated\ usuallycationic\ metal carbonyl complexes since NuH is always a much weaker nucleophile than Nu−

ð64IC1037\ 65IC1235\ 68IC0054\ 79AOC"07#0\ 73OM0412\ 74OM489Ł[ The attack of the nitrogen nucleophileon metal carbonyls "M�Fe\ Ni# can be aided by Y groups which make the nitrogen electron rich\thus promoting nucleophilic attack "Y�Li\ MgX "X�Hal#\ HgR\ C"NMe2#2\ HB"OR#1\ B"OR#2#ð72OM0933Ł[


CarbamoylÐmetal complexes can be synthesized by using an electron!rich transition!metal com!plex to displace a halide from an organic carbamoyl halide[ For example\ FeCp"CO#1CONR1

"R�Me\ Et# has been synthesized in this way ð52JA0807Ł[ WCp"CO#1CONHMe "062# has beenmade in the reaction of WCp"CO#1Me "060# with hydrogen isocyanate "061# "Equation "31##ð61JA2688Ł[ Trans!ðPt"PPh2#1"CNMe#CONHMeŁ¦ "064# has been made by the attack of hydroxideion on trans!ðPt"PPh2#1"CNMe#1Ł1¦ "063# "Equation "32## ð60JA4313Ł[

Me

WCp CO

CO

WCp CO

CO

O NHMeHNCO(172)

(171) (173)

(42)

(43)

CNMe

PtMeNC PPh3

PPh3

PtMeNC PPh3

PPh3

O NHMe

(174) (175)

+ HO–

5[05[1 FUNCTIONS CONTAINING AT LEAST ONE PHOSPHORUS\ ARSENIC\ANTIMONY OR BISMUTH FUNCTION "AND NO HALOGEN\ CHALCOGEN ORNITROGEN FUNCTIONS#

5[05[1[0 Carbonyl Derivatives with Two P\ As\ Sb or Bi Functions

Carbonyl bis"diphenylphosphide# "067# may be synthesized by adding a solution of diphenyl!"trimethylsilyl#phosgene "066# in diethyl ether dropwise to a solution of phosgene "065# in diethyl!


ether at −099>C under nitrogen[ The reported yield is 39) and involves the production oftrimethylsilyl chloride "068# "Equation "33## ð62AG"E#731Ł[

O

Cl Cl

O

Ph2P PPh2

+ 2 TMS-Cl+ 2 TMS-PPh2

Et2O, 100 °C

40%(44)

(176) (177) (178) (179)

Treatment of Cl1P"O#CH1CHOEt "079# with NOCl "070# in carbon tetrachloride at 9>C gives areported 74) yield of Cl1P"O#CH"NO#CH"OEt#Cl "071# which\ on ethanolysis\ gives a mixturecontaining Cl1CHOEt "072#\ EtO1CNHCH"OEt#1 "073#\ "EtO#1P"O#CONHCH"OEt#1 "074# andð"EtO#1P"O#Ł1CO "075# "Scheme 07# ð79MI 505!90Ł[ Carbonylbis"phosphonates# "077# are preparedby alkaline hydrolysis of a salt of a dihalomethylenediphosphonic acid "076#[ Thus\ compound "076#and sodium hydroxide are re~uxed for 0Ð5 h in water to yield 52) of compound "077# "Equation"34## ð56JOC3000\ 69USP2386202Ł[

Scheme 18

O

PEtO

EtOP

O

OEt

OOEt

O

PEtO

EtON

O

H

(185)

OEt

OEt

O

EtO N OEt

+ NOCl

H

EtOH

OEtOEt

Cl Cl

(180) (182)(181)

+

CCl4, 0 °C

85%

(186)(184)(183)

+ +

O

PCl

Cl

OEt

O

PCl

Cl

NO

OEt

Cl

O

P P–O

O

O–

O–O O–

(188)

4 Na–

POH

OOH

PHO O

OH

Cl

Cl

(187)

NaOH, H2O, pH > 10.5

63%(45)

Metal carbonyl complexes have also been prepared containing phosphorus ligands bridged bycarbonyl groups ð89JOM"272#184Ł[ The addition of Pri

1NPCl1 "089# to a solution of Na1Fe"CO#3 "078#in ether at −67>C\ followed by 13 h stirring at room temperature\ results in the isolation of a 24)yield of "Pri

1NP#1COFe1"CO#5 "080#[ The amine must be sterically hindered for this reaction tosucceed "Equation "35## ð74IC3338\ 76JA6653Ł[ These compounds may also be prepared by insertingcarbon monoxide into a P0P bond[ The reaction of the iron complex "081# with carbon monoxideat 79>C and 49 atm pressure results in the isolation of the phosphorus!bridging carbonyl derivative"082# as the major product "Equation "36## ð75AG"E#644\ 75ZN"B#172\ 76CB0310Ł[

NPri2

FeP

Fe

PO

NPri2

OC COOC

CO CO

CO

(191)

Na2Fe(CO)4 + Pri2NPCl2

Et2O

35%

(190)(189)

(46)

But

FeP

Fe

PO

But

OC COOC

CO CO

CO

(193)(192)

But

FeP

Fe

P

But

OC COOC

CO CO

CO

(47)+ CO

80 °C, 50 atm


Phosphoureas\ such as 0\2!bis"trimethylsilyl# substituted diphosphourea derivatives "083#\ maybe cyclized to form 0\2!di!t!butyl!1!alkyl!0\1\2!triphosphetan!3!ones "087# in good yield[ The reac!tion takes place at room temperature in toluene over 01Ð25 h "Scheme 08# ð72CB1260Ł[

R = Me, Ph, But

P

O-TMS

P

P

But

But

Cl

R

P

O

P

P

But

But

Cl

R

TMS

(196) (197)

PP

P

O

But

But But

+RPCl2

–TMS-Cl

(195)(194)

–TMS-Cl

(198)

O

P PBut

TMS

But

TMS

P

O-TMS

P

TMS

But

But

Scheme 19

No references were found to carbonyl derivatives with two As\ Sb or Bi functions[

5[05[1[1 Carbonyl Derivatives with One P\ As\ Sb or Bi Function Together with a Metalloid or MetalFunction

No references were found for carbonyl derivatives either with one P\ As\ Sb or Bi functiontogether with a metalloid function or with one As\ Sb or Bi function together with a metal function[There are\ however\ reports of carbonyl derivatives with one phosphorus and a metal function[They are made by carbon monoxide insertion into metalÐphosphorus bonds[ For example\Cp�HfCl1"PBut

1# "088# "Cp��h4!C4Me4# has been shown to react with 0 equivalent of carbonmonoxide within minutes at 14>C to generate the insertion product "199# "Equation "37## ð74JA3569\76JCS"D#1928\ 77CRV0948Ł[

But

PHf

But

Cl

Cp*

Cl

P(But)

Hf

O

Cl

Cp*

Cl

(200)(199)

CO, 2 atm, 25 °C

73%(48)

5[05[2 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION "AND NOHALOGEN\ CHALCOGEN OR GROUP 4 ELEMENT FUNCTIONS#

5[05[2[0 Carbonyl Derivatives with Two Silicon Functions

Bis"silyl# ketones may be prepared by the oxidation of the corresponding carbinol[ For example\bis"triphenylsilyl# ketone "191# has been synthesized by oxidizing 0\0!bis"triphenylsilyl#methanol"190# with chromium trioxide and sulfuric acid in diethylether at room temperature for 34 min"25) yield#^ by reacting the methanol derivative "190# in ether successively with dcc\ pyridiniumtri~uoroacetate and DMSO and stirring for 01 h at room temperature "15) yield#^ and by oxidizingthe methanol derivative "190# in carbon tetrachloride solution with benzoyl peroxide and N!bromo!succinimide at 54>C "5) yield# "Equation "38## ð57CJC1008Ł[

(202)(201)

oxidation(49)

SiPh3

Ph3Si OH

O

Ph3Si SiPh3


Bis"trimethylsilyl# ketone "194# has been prepared by the reaction of the bis!silylated ylide "192#with the freshly prepared adduct formed from ozone and triphenylphosphite "193# in toluene at−67>C for 4 h "Equation "49## ð74AG"E#0957\ 81AG"E#0953Ł[

(205)(203)

toluene, –78 °C, 5 h

50%(50)

O

TMS TMS

PPh3

TMS TMS+ O3•P(OPh)3

(204)

The oxidation of tris"trimethylsilyl#!methylthiomethane "195# with m!chloroperoxybenzoic acid"mcpba# leads to bis"trimethylsilyl# ketone "194# under very mild conditions[ A solution of mcpbain dichloromethane is added slowly\ under nitrogen\ to a solution of the thiomethane derivative"195# in dichloromethane at −67>C[ After 09 min stirring and workup\ the ketone "194# is isolatedin 34) yield "Equation "40## ð75TL4874Ł[

(205)(206)

O

TMS TMS

TMS

TMS S

TMS CH2Cl2, mcpba (207), –78 °C

45%Me (51)

5[05[2[1 Carbonyl Derivatives with Two Boron Functions

No references were found to carbonyl derivatives with two boron functions[

5[05[2[2 Other Carbonyl Derivatives with Two Dissimilar Metalloid Functions

Germyl silyl ketones have been prepared by hydrolysing the corresponding 1!substituted 0\2!dithianes[ For example\ triethylgermyl trimethylsilyl ketone "100# is synthesized by reacting1!triethylgermyl!0\2!dithiane "197# with n!butyllithium in THF over 0Ð2 h at −19>C to form thecarbanion which readily reacts with trimethylsilyl chloride at 9>C to form 1!triethylgermyl!1!trimethylsilyl!0\2!dithiane "198# in 68) yield[ Hydrolysis of the dithiane "198# with mercuric chloride"109# and cadmium carbonate in 09) water in methanolÐTHF at 14>C over 89 min yielded therequired ketone "100# "Scheme 19# ð56JA320Ł[

S

S

GeEt3S

S GeEt3

TMS

O

TMS GeEt3

i, BunLi

ii, TMS-Cl

CdCO3

HgCl2 (210)

(208) (209) (211)

Scheme 20

5[05[2[3 Carbonyl Derivatives with One Metalloid and One Metal Function

Transition!metal acylsilanes have been of some interest since the preparation of the _rst transition!metal!bonded acylsilane\ fac!Re"CO#2"diphos#ðCOSiPh2Ł "104#[ It is prepared by adding a THFsolution of Ph2SiLi to a slurry of ðRe"CO#3"diphos#ŁðClO3Ł "103# in THF at 14>C and reacting for89 min[ The transition!metal!bonded acylsilane "104# was isolated as air!stable purple crystals in14Ð29) yield "Scheme 10# ð65JA3567Ł[

410Two Metals

Re

CO

COOCOC

CO

Ph3Si O

Re

CO

CO

POCOC

PRe

CO

CO

POCOC

PClO4

–

+

(214) (215)

Re(CO)5Cldiphos i, AlCl3, CO

ii, HClO4

Ph3SiLi

(212) (213)

Scheme 21

Reaction of Cp1Zr"TMS#Cl "105# with carbon monoxide "578 kPa# provides the silaacyl Cp1Zr"h1!CO!TMS#Cl "106# and the _rst observation of carbon monoxide insertion into a transitionmetalÐsilicon bond[ The complex "106# was isolated in 89) yield[ "Equation "41## ð76JA1938Ł[

TMS

Cp2Zr

Cl

Cp2Zr

Cl

TMS

O

(216) (217)

Et2O, +CO, 689 kPa

–CO(52)

Pentane solutions of Cp1ZrðSi"TMS#2ŁTMS "107# react rapidly with carbon monoxide "578 kPa#to give an orange solution from which the silaacyl Cp1Zr"h1!COTMS#ðSi"TMS#2Ł "108# can becrystallized in 64) yield "Equation "42##[ This reaction is generally applicable and the carbonmonoxide insertion reaction of transition!metal silyl compounds has been widely reported ð74JA3973\74JA5398\ 75JA4244Ł[

Si(TMS)3

Cp2Zr

TMS

Cp2Zr

Si(TMS)3

TMS

O

(218) (219)

pentane, +CO, 689 kPa

75%(53)

5[05[3 CARBONYL DERIVATIVES CONTAINING TWO METAL FUNCTIONS

5[05[3[0 Metal Carbonyl Complexes and Fluxionality

Carbon monoxide reacts with transition metals to form transition!metal carbonyl complexes[Where two or more atoms of the transition metal are incorporated into the organometallic complex\the carbonyls adopt either a terminal or a bridged con_guration[ The energy di}erence betweenterminal and bridging carbonyls is usually low\ so a ~uxionality exists between the con_gurations[The compound "119# contains both terminal and bridging carbonyl ligands ð73AOC"12#108Ł[ In asimple C!bonded bridge\ the carbon monoxide ligand is perpendicular to the metalÐmetal axis andthe carbon is equally bound to both metals\ whereas the CO ligand may also be preferentially boundto one or other of the metal atoms in the bridging carbonyl complex[ The carbon monoxide ligandis usually bound to two or more metal atoms in one of the ways shown in Figure 0[ In "a# the M0Cbonds are of equal length^ in "b# the M0C bond lengths are signi_cantly di}erent^ in "c# and "d#the carbon monoxide ligand is triply bridging\ with the obvious di}erences between the bondlengths[

Ru Ru

O

O

Cp

OC

Cp

CO

(220)

M

MCO

M

M CO

MM

MCO

MM

MCO

(a) (b) (c) (d)

Figure 1


If a metal carbonyl complex is synthesized in which there is more than one metal atom\ some orall of the carbon monoxide ligands may bridge between two or more of the metal atoms[ Sometransition metals form only monomer complexes and so carbonyl bridging is impossible[ Thecarbonyl!bridged transition!metal complexes are polymers of metal carbonyls where polymerizationis possible[

5[05[3[1 Preparation of Metal Carbonyls

A large number of metal carbonyls is known and the following survey is intended to provide abrief summary of methods of preparation of the more common compounds[ For more information\appropriate volumes of Comprehensive Or`anometallic Chemistry and a specialist monographðB!82MI 505!90Ł should be consulted[

5[05[3[1[0 Metal carbonyls of titanium\ zirconium and hafnium

Titanium hexacarbonyl ðTi"CO#5Ł has been produced by condensation of titanium metal vapourwith carbon monoxide in a matrix of inert gases at 09Ð04 K and identi_ed spectroscopicallyð66IC711Ł[ The cyclopentadienyl derivative\ Ti"C4H4#1"CO#1\ has been prepared by treatingTiCl1"C4H4#1 with sodium cyclopentadienide and carbon monoxide under pressure ð50JA0176Ł[ The_rst hafnium carbonyl\ "h4!C4H4#1Hf"CO#1\ was prepared and studied by Sikora et al[ ð68JA4968Ł[None of the above transition metal carbonyl complexes contains bridging carbon monoxide ligands[

5[05[3[1[1 Metal carbonyls of vanadium\ niobium and tantalum

Reduction of vanadium trichloride "VCl2# by sodium in pyridine under 199 atm of carbonmonoxide yields\ following workup\ the vanadium hexacarbonyl ðV"CO#5Ł "an odd!electron tran!sition!metal carbonyl complex#\ which cannot be isolated[ The noble gas con_guration is attainedin the isolable anionic intermediate ðV"CO#5Ł− or in the super!reduced 07!electron species ðV"CO#4Ł2−

ð70JA5099Ł[ A direct synthesis of V"CO#5 and the dimer V1"CO#01 by condensation with carbonmonoxide in a matrix of noble gases has been reported ð65IC0555Ł[ All the transition!metal carbonylcomplexes of this group are extremely unstable[

5[05[3[1[2 Metal carbonyls of chromium\ molybdenum and tungsten

This is the _rst group to be discussed in which metal carbonyls have been known for some timeand are quite stable[ Molybdenum hexacarbonyl\ Mo"CO#5\ chromium hexacarbonyl\ Cr"CO#5\ andtungsten hexacarbonyl\ W"CO#5\ were all prepared for the _rst time in the early part of the twentiethcentury ð09JCS687\ 16BSF0930\ 17CR"076#453Ł[ The monomers have been made by the reaction of carbonmonoxide at 199Ð149 atm and 199Ð299>C with the metals "M�Mo\ W# ð29GEP420391\ 20GEP436914Łby reacting anhydrous metal"III# chloride "M�Cr# or metal"V# chloride "M�Mo\ W# with phenyl!magnesium bromide and carbon monoxide at 3>C and 0 atm and hydrolysing the reaction productsð16BSF0930\ 24ZAAC"110#210\ 36JA0612\ 49IS045Ł by reacting the metal chlorides with carbon monoxideat 099 atm and 9Ð09>C in the presence of zinc or iron powders "M�Mo\ W# ð39DOK"15#43\39DOK"15#46Ł[

Chromium hexacarbonyl has also been prepared using a metalÐpyridine system as the reducingagent[ The reaction of anhydrous pyridine\ magnesium powder and small amounts of iodine wasused to carbonylate chromium"III# and chromium"II# salts at 029Ð079>C and 099Ð299 atm for 3Ð01 h ð46JA2500\ 48G798Ł[ Lithium aluminum hydride has also been used as the reducing agent ð48MI505!91Ł[

The most versatile method of preparing the hexacarbonyls of this group is the reductive car!bonylation with trialkylaluminum compounds\ for which yields of 81)\ 65) and 81) have beenreported for Cr"CO#5\ Mo"CO#5 and W"CO#5\ respectively ð59JA0214Ł[

Reduction of the hexacarbonyls with a borohydride in liquid ammonia forms dimericðM1"CO#09Ł1−[ Chromium hexacarbonyl Cr"CO#5 forms chromocene Cr"h4!C4H4#1 on reaction with

412Two Metals

sodium cyclopentadienide\ while under the same conditions the molybdenum and tungsten hexa!carbonyls form only ð"h4!C4H4#M"CO#2Ł1[ The chromium analogue of these dimers can also beformed ðB!73MI 505!90Ł[

5[05[3[1[3 Metal carbonyls of manganese\ technetium and rhenium

Decacarbonyldirhenium\ Rh1"CO#09 was _rst prepared in 0830 by Hieber and Fuchsð30ZAAC"137#145Ł[ Decacarbonyldimanganese\ Mn1"CO#09\ was prepared and fully characterized in0843 by Brimm et al[ ð43JA2720Ł and the synthesis of decacarbonylditechnetium\ Tc1"CO#09\ was_rst described in 0850 ð50AG468\ 50JA1842\ 54ZN"B#0048Ł[

"i# Decacarbonyldiman`anese

Decacarbonyldimanganese has been prepared by reacting carbon monoxide at 199 atm at roomtemperature for 04Ð06 h with a mixture of magnesium powder\ manganese iodide\ copper andcopper iodide suspended in diethyl ether ð43JA2720Ł\ by the action of phenylmagnesium bromide orchloride and carbon monoxide at 29 atm on anhydrous MnCl1 in diethyl ether at −19 to 29>Cð47USP1711136Ł\ and by reducing manganese"II# salts with sodium benzophenone ketyl in THF\carbonylating the resulting mixture with carbon monoxide at 199Ð699 atm and 54Ð199>C andhydrolysing and steam distilling the Mn1"CO#09 from the resulting mixture ð47JA5056Ł[ The reductionof an anhydrous manganese"II# salt with a trialkylaluminum compound dissolved in an ether orbenzene in the presence of carbon monoxide under pressure results in a 59) yield of the requiredcompound ð47IZV099\ 59JA0214\ 54IC182Ł[

"ii# Decacarbonylditechnetium

This carbonyl has been prepared by the action of carbon monoxide at 149Ð249 atm on theheptoxide Tc1O6 at 119Ð164>C for 01Ð19 h ð50AG468\ 50JA1842\ B!53MI 505!90\ 54ZN"B#0048Ł[

"iii# Decacarbonyldirhenium and hi`her polymers of rhenium hexacarbonyl

Rhenium heptoxide\ Re1O6\ is reduced by carbon monoxide at high temperature and pressure togive Re1"CO#09 "110# "Equation "43## ð30ZAAC"137#145Ł[ The reaction of ReCl4 or ReCl2 with carbonmonoxide at 029>C and 149Ð179 atm for 7 h using sodium in THF as the reducing agent hasyielded 69) of Re1"CO#09 ð52JCS0022Ł[ The polynuclear tetracarbonylrhenium\ ðRe"CO#3Łn\ has beenprepared by reacting Re1S6 with carbon monoxide "74 atm# at 199>C in the presence of copperpowder[

Re2O7 + 17 CO Re2(CO)10 + 7 CO2

(221)

(54)

5[05[3[1[4 Metal carbonyls of iron\ ruthenium and osmium

"i# Iron carbonyls

The transition!metal carbonyls Fe1"CO#8 "111# and Fe2"CO#01 "112# are obtained by the action ofsunlight on Fe"CO#4 in glacial acetic acid or in acetic anhydride in vacuo ð16CB0313\ 18MI 505!90Ł[ Thetrimer "112# may also be prepared by oxidizing alkaline solutions containing carbonylferrates withmanganese dioxide\ MnO1\ followed by removal of excess MnO1\ acidi_cation and extraction of thecarbonyl with petroleum ether ð46ZAAC"178#213Ł[ The cyclopentadienyl iron carbonyl dimer "113#


has been prepared by reacting iron pentacarbonyl and dicyclopentadiene at 024>C in an auto!clave[ Prolonged reaction of the same reactants produces the tetrameric cluster compound\ðFe"h4!C4H4#"CO#Ł3\ which involves CO groups which are triply bridging ðB!67MI 505!90Ł[

Fe Fe

O

O

OC

OC

CO

CO

OC CO

O

Fe

Fe

O

OCCO

CO

O

Fe

CO

CO

OC

OCOC

OC

CO

Fe

Fe

COCO

Fe

CO

CO

OC

OCCO

COCOOC

COCO

Fe Fe

O

O

OC

OC

CO

CO

(223) (224)(222)

"ii# Ruthenium carbonyls

Both Ru"CO#4 and Ru2"CO#01 are formed when RuI2 is mixed with a large excess of silver powderand kept at 069>C for 13 h under carbon monoxide at about 349 atm in a rotating autoclave[ Thetrimer is prepared from the monomer by heating it in hydrocarbons or alcohols for a short time inthe presence of light ð25ZAAC"115#274Ł[

When ruthenium"III# acetylacetonate reacts with carbon monoxide and hydrogen "2 ] 0# underpressure "049Ð199 atm# at 039Ð059>C in acetone\ benzene or methanol\ yields as high as 71) ofRu2"CO#01 are obtained ð53CI"M#195Ł[

"iii# Osmium carbonyls

The carbonyls Os"CO#4 and Os2"CO#01 are formed when the halides "OsCl2 and Os1Br8# and anoxyiodide are mixed with powdered copper or silver and reacted with carbon monoxide at highpressure "199Ð299 atm# and temperature "049Ð299>C# ð32MI 505!90Ł[

5[05[3[1[5 Metal carbonyls of cobalt\ rhodium and iridium

Mononuclear carbonyls are not formed with this group of transition metals as the elements ofthis group can only satisfy the 07!electron rule in their carbonyls if metalÐmetal bonds are present[However\ multinuclear carbonyls such as Co5"CO#05\ Rh5"CO#05 and Ir3"CO#01 are readily formedð39ZAAC"134#210\ 55JA0710\ 56CC339Ł[

"i# Cobalt carbonyls

The octacarbonyl Co1"CO#7 has been prepared by the reaction of carbon monoxide at 29Ð39 atmand 049>C with _nely divided cobalt ð09JCS687Ł or by reacting cobalt halides and sul_des withcarbon monoxide in the presence of reducing metals\ such as copper ð28ZAAC"139#150Ł[ By treatingCoSO3 or CoCl1 in aqueous ammonia solution with carbon monoxide "84Ð009 atm# at 019Ð039>Cfor 05Ð07 h a yield of 59) of the required carbonyl may also be obtained ð42LA"471#005Ł[

Adkins and Krsek prepared solutions of Co1"CO#7 by reacting Raney cobalt suspended in diethylether with carbon monoxide at about 149 atm and 049>C ð37JA272Ł[ According to a Japanese patent\Co1O2 suspended in benzene is transformed into the carbonyl by reaction with carbon monoxideand hydrogen at 199 atm and 009>C in the presence of some pyridine and preformed Co1"CO#7ð45JAP09813Ł[ Another way to synthesize octacarbonyldicobalt is to use high pressures of carbonmonoxide "099Ð199 atm# at high temperatures "039Ð299>C# with anhydrous cobalt salts of organicor inorganic acids dissolved or suspended in nonaqueous media\ using hydrogen as the reducingagent[ The reaction is accelerated by the addition of preformed Co1"CO#7 ð38USP1362882\ 38USP1365152\38USP1366442\ 38USP1366443\ 59CI"M#022\ 59CI"M#026Ł[

The carbonyl Co3"CO#01 "115# is prepared by heating Co1"CO#7 "114# to 59>C for 13 h in aninert atmosphere with the evolution of carbon monoxide "Equation "44## ð09JCS687Ł\ or by usinghydrocarbons as solvents in the reaction ð44CI"M#5\ 44JA2840Ł[ A method has also been reported for

414Two Metals

the preparation of Co3"CO#01 "116# from cobalt"II# ethylhexanoate or cobalt"II# and cobalt"III#acetylacetonates[ These are reacted with hydrogen at 29Ð49 atm and with Co1"CO#7\ giving yieldsof over 89) "Equation "45## ð48CI"M#021Ł[

2 [Co2(CO)8] Co4(CO)12 + 4 CO60 °C

(55)

(225) (226)

2 (RCO2)2Co + 3 Co2(CO)8 + 2 H2 Co4(CO)12 + 4 RCO2H

(227)

(56)

"ii# Rhodium carbonyls

When rhodium metal is reacted at 199>C with carbon monoxide "349 atm# for 04 h\ the dimerRh1"CO#7 can be isolated[ The reaction of anhydrous RhCl2 and carbon monoxide at 199 atm for04 h in the presence of copper "or silver\ cadmium or zinc# results in the isolation of the otherpolymers[ At 49Ð79>C\ the tetramer Rh3"CO#01 is formed\ whereas at 79Ð129>C only Rh5"CO#05 ispresent ð32ZAAC"140#85Ł[

"iii# Iridium carbonyls

The reaction of iridium halides\ IrX2\ with carbon monoxide at 249 atm for 13Ð37 h at 099Ð039>Cin the presence of copper yields a mixture of Ir3"CO#01 and ðIr"CO#3Łn[ Separation is based on thesolubility of ðIr"CO#3Łn in ether and carbon tetrachloride relative to that of Ir3"CO#01

ð39ZAAC"134#210Ł[

5[05[3[1[6 Metal carbonyls of nickel\ palladium and platinum

The _rst transition!metal carbonyl to be discovered was nickel tetracarbonyl\ Ni"CO#3\ and it isused to produce metallic nickel[ Reduction of Ni"CO#3 leads to a number of polynuclear carbonylateanion clusters such as ðNi4"CO#01Ł1− and ðNi5"CO#01Ł1− ðB!73MI 505!90Ł[

Alkaline reduction of ðPtCl5Ł1− in an atmosphere of carbon monoxide yields a series of platinumcarbonylate anion clusters\ ðPt2"CO#5Łn1−[ By re~uxing salts of the n�2 anion in acetonitrile\ thecluster anion ðPt08"CO#11Ł3− has been obtained ð68JA5009Ł[

5[05[3[1[7 Metal carbonyls of copper\ silver and gold

Neutral binary carbonyls are not formed by these metals at room temperature\ but some have beensynthesized by the condensation of copper or silver vapour and carbon monoxide at temperatures of5Ð04 K "e[g[\ M1"CO#5# ð65JA2056Ł[

5[05[3[1[8 Mixed metal carbonyls

These are prepared by reacting a halogenocarbonylmetal with carbonylmetallates of alkali metals"Equations "46#\ "47#\ "48#\ and "59##[ The reactions are carried out in an ether\ such as THF\ andoccur very rapidly[

NaMn(CO)5 + ReCl(CO)5 NaCl + (CO)5MnRe(CO)5 (57)

NaCo(CO)4 + MnBr(CO)5 NaBr + (CO)4CoMn(CO)5 (58)

NaCo(CO)4 + Fe(C5H5)(CO)2I NaI + (CO)4CoFe(C5H5)(CO)2 (59)


NaRe(CO)5 + Fe(C5H5)(CO)2Cl NaCl + (CO)5ReFe(C5H5)(CO)2 (60)

The anion ðFeCo2"CO#01Ł− has been prepared by reacting Co1"CO#7 with Fe"CO#4 in the presenceof acetone ð59G0994Ł[ Ultraviolet radiation of a hexane solution of Fe"CO#4 and Mn1"CO#09 resultsin the formation of the mixed metal carbonyl ð"CO#4MnŁ1Fe"CO#3 ð54ZN"B#0295Ł[ Warming a THFsolution of the salt ðMn"CO#5ŁðCo"CO#3Ł to room temperature results in the formation of "CO#4MnCo"CO#3 ð53CB1178Ł[


6.17Functions Containing aThiocarbonyl Group and atLeast One Halogen; Also atLeast One Chalcogen and NoHalogenERICH KLEINPETERUniversity of Potsdam, Germany

and

KALEVI PIHLAJAUniversity of Turku, Finland

5[06[0 FUNCTIONS CONTAINING AT LEAST ONE HALOGEN 417

5[06[0[0 Thiocarbonyl Halides with Two Similar Haloèns 4175[06[0[0[0 Thiocarbonyl di~uoride 4175[06[0[0[1 Thiocarbonyl dichloride "thiophosène# 4185[06[0[0[2 Thiocarbonyl dibromide 4185[06[0[0[3 Thiocarbonyl diiodide 4295[06[0[0[4 Sulfoxides of thiocarbonyl halides "sul_nes# with two similar haloèns 429

5[06[0[1 Thiocarbonyl Halides with Two Dissimilar Haloèns 4205[06[0[1[0 Thiocarbonyl chloride ~uoride 4205[06[0[1[1 Thiocarbonyl bromide ~uoride 4215[06[0[1[2 Thiocarbonyl bromide chloride 4215[06[0[1[3 Sulfoxides of thiocarbonyl halides "sul_nes# with two dissimilar haloèns 421

5[06[0[2 Thiocarbonyl Halides with One Haloèn and one Other Heteroatom Function 4225[06[0[2[0 Fluorothioformates ROC"F#1S 4225[06[0[2[1 Chlorothioformates ROC"Cl#1S 4225[06[0[2[2 Fluorodithioformates RSC"F#1S 4235[06[0[2[3 Chlorodithioformates RSC"Cl#1S 4245[06[0[2[4 Bromodithioformates RSC"Br#1S 4255[06[0[2[5 Fluoroselenothioformates RSeC"F#1S 4255[06[0[2[6 Chloroselenothioformates RSeC"Cl#1S 4255[06[0[2[7 Bromoselenothioformates RSeC"Br#1S 4265[06[0[2[8 Sul_nes derived from CF2SeC"Cl#1S and CF2SeC"Br#1S 4265[06[0[2[09 Thiocarbamoyl ~uorides R1NC"F#1S 4265[06[0[2[00 Thiocarbamoyl chlorides R1NC"Cl#1S 4265[06[0[2[01 Thiocarbamoyl bromides R1NC"Br#1S 439

416

417 Thiocarbonyl and Halo`en or Chalco`en

5[06[1 FUNCTIONS CONTAINING AT LEAST ONE CHALCOGEN FUNCTION"AND NO HALOGEN# 439

5[06[1[0 Thionocarbonates "O\O!Diesters of Thiocarbonic Acid# 4395[06[1[1 Dithiocarbonates "O\S!Diesters of Dithiocarbonic Acid# 434

5[06[1[1[0 Salts of O!alkyl esters of dithiocarbonic acid 4345[06[1[1[1 O\ S!Diesters of dithiocarbonic acids 434

5[06[1[2 Derivatives of Trithiocarbonic Acid 4415[06[1[2[0 Salts of monoesters of trithiocarbonic acid 4415[06[1[2[1 Diesters of trithiocarbonic acid 441

5[06[1[3 Derivatives of Thiocarbamic Acid 4445[06[1[3[0 O!Esters of thiocarbamic acids 445

5[06[1[4 Derivatives of Dithiocarbamic Acid 4595[06[1[4[0 Salts of dithiocarbamic acids 4595[06[1[4[1 Esters of dithiocarbamic acids 450

5[06[0 FUNCTIONS CONTAINING AT LEAST ONE HALOGEN

Functions containing at least one halogen have been described in a volume of Houben!Weylð72HOU"E3#396Ł published in 0872[ Thus the literature search for related compounds in Chapter5[06 is based on Chemical Abstracts from 0879 to February 0883[ The present text concentrateson literature from the mid 0879s^ original references to synthetic methods given in Volume E3 ofHouben!Weyl are mentioned only in order to locate them in cases of need[ Volume E3 of Houben!Weyl can be strongly recommended because it includes detailed synthetic procedures ð72HOU"E3#396\72HOU"E3#319Ł[

A number of clathrate compounds have proved useful for facilitating the handling of thiophosgeneand similar reactive reagents ð81TL150Ł[

5[06[0[0 Thiocarbonyl Halides with Two Similar Halogens

5[06[0[0[0 Thiocarbonyl di~uoride

"i# From 1\1\3\3!tetra~uoro!0\2!dithietane

Middleton et al[ ð50JA1478\ 54JOC0264Ł prepared thiocarbonyl di~uoride F1C1S "a colorless gasboiling at −43>C# ð54JOC0264Ł in high purity and yield "×89)# by a three!step procedure^ _rstthiophosgene was dimerized and the dimer ~uorinated with SbF2[ Pyrolysis of the resulting 1\1\3\3!tetra~uoro!0\2!dithietane at 364Ð499>C led to thiocarbonyl di~uoride in nearly quantitative yield"Scheme 0#[

S

Cl

Cl

S

F

F

S

S

Cl

ClCl

Cl S

S

F

FF

F

Scheme 1

2 2

"ii# Other methods

Thiocarbonyl di~uoride was also obtained as a by!product of the reaction of bis"tri~uoromethyl#trisul_de with Grignard reagents RMgX "R�Et\ Pri# ð81JFC"48#80\ 82JFC"59#74Ł[ Middleton et al[ð54JOC0264Ł also obtained thiocarbonyl di~uoride from tetra~uoroethylene by reaction with sulfurat 349Ð499>C[ It was obtained in even higher yield "85)# by Marquis ð59USP1851418Ł from chloro!di~uoromethane by bubbling it through sulfur at 259>C[ Further F1C1S was obtained from thesulfenyl chloride FCl1CSCl by reduction with tin and concentrated HCl but in lower yield "36[4)#ð48ZOB2681Ł[

418At Least One Halo`en

5[06[0[0[1 Thiocarbonyl dichloride "thiophosgene#

"i# From trichloromethanesulfenyl chloride and other perchloromethyl derivatives containin` sulfur

One of the most useful methods for the synthesis of thiophosgene is the reduction of perchloro!methyl sulfenylchloride with H1S at 009Ð003>C^ this gives thiophosgene in 85) yield ð63S15Ł[ Anumber of other reducing agents have been used ð72HOU"E3#396Ł\ including tin and concentratedHCl "Equation "0## ð78JAP92959307Ł[

S

Cl

Clred.

Cl3C SCl (1)

Alternatively\ perchloromethyl derivatives containing sulfur can be thermally decomposedð54GEP0108344Ł[ A number of synthetic procedures are published which optimize the thiophosgeneyield^ in particular\ aqueous H1SO2 in the presence of catalysts "S1Cl1\ SCl1\ alkali metal iodideand:or I1# proved useful ð78JAP92926009\ 78JAP92959306\ 78JAP92959307\ 78JAP92086209\ 80JAP92959308Ł[

"ii# From trichloromethyl thiol

Thiophosgene\ a red liquid boiling at 62[4>C ð72HOU"E3#396Ł was also prepared by reducingtrichloromethyl thiol with SO1 in the presence of KI and S1Cl1 ð74JAP51002601\ 77JAP90146005Ł[When H1S was used in place of S1Cl1\ the yields obtained were higher than 86) "Equation "1##ð75JAP51065809Ł[

S

Cl

ClSO2

Cl3C SH (2)

"iii# From carbon monosul_de

Thiophosgene can be obtained from carbon monosul_de CS "continuously produced by dis!sociation of CS1 in a high!frequency discharge at 9[0 torr "mm Hg## ð63IC0667Ł by reaction with Cl1at room temperature ð56AG538\ 57ZAAC"250#079Ł[

5[06[0[0[2 Thiocarbonyl dibromide

"i# From carbon monosul_de

Carbon monosul_de\ continuously produced by dissociation of CS1 in a high!frequency discharge"9[0 torr "mm Hg##\ ð63IC0667Ł reacts at room temperature with Br1 giving thiocarbonyl dibromideð56AG538\ 57ZAAC"250#079Ł[ This compound is an orangeÐred liquid boiling at 031Ð033>Cð54JOC0264Ł[

"ii# Other methods

Thiocarbonyl dibromide was obtained from F1C1S in 86) yield ð54JOC0264Ł by addition ofanhydrous hydrogen bromide^ thiol intermediates eliminate the hydrogen ~uoride "Equation "2##[Thiocarbonyl dibromide could also be obtained from thiophosgene but only in 20) yield ð70CB718Ł^the halogens were exchanged in this case with BBr2 at 59Ð54>C[


S

Br

Br

S

F

F(3)

+2HBr

–2HF

5[06[0[0[3 Thiocarbonyl diiodide

"i# From carbon monosul_de

Thiocarbonyl diiodide can be synthesized in a similar way to thiophosgene and thiocarbonyldibromide\ from carbon monosul_de by reaction with I1 ð56AG538\ 57ZAAC"250#079Ł[ Although thediiodide could not be isolated\ it was identi_ed by IR spectroscopy "nC1S�0951 cm−0^ nC0I�591cm−0# ð56AG538\ 57ZAAC"250#079Ł[

5[06[0[0[4 Sulfoxides of thiocarbonyl halides "sul_nes# with two similar halogens

"i# Di~uorosul_ne\ F1C1SO

"a# From 0\0\3\3!tetra~uorodithietane[ It was much more di.cult to obtain this compound thanthe corresponding dichlorosul_ne Cl1C1SO "see below#[ 1\1\3\3!Tetra~uoro!0\2!dithietane waseasily oxidized with tri~uorotriacetic acid "in dichloromethane at 9>C# to 1\1\3\3!tetra~uoro!0\2!dithietane!0!oxide^ however\ to get the corresponding 0\2!dioxide\ Henn and Sundermeyerð77JFC"28#218Ł only succeeded by employing tri~uoromethanetrisulfonic acid as a new oxidizingagent "Scheme 1#^ pyrolysis at 379>C and 9[90 torr "mm Hg# yields F1C1SO quantitatively[Di~uorosul_ne was detected only by mass spectrometry and decomposes spontaneously at −099>Cto F1C1O and sulfur[

S

F

F

S

S

F

FF

F S

S

F

FF

F

O

S

S

F

FF

F

O

O

O

Scheme 2

MeCO3H, CH2Cl2, 0 °C

63%

F3CSO4H, 0 °C

39%

∆

"b# From allyl di~uorochloromethyl sulfoxide[ F1C1SO could also be obtained by pyrolysis ofF1ClCS"O#CH1CH1CH1 at 299Ð399>C ð75CB158Ł^ again\ it was identi_ed by mass spectrometry[

"ii# Dichlorosul_ne Cl1C1SO

The synthesis\ structure\ analysis\ and chemistry of thiophosgene!S!oxide "dichlorosul_ne# havebeen reviewed ð81SUL164Ł[

"a# From 1\1\3\3!tetrachloro!0\2!dithietane[ 1\1\3\3!Tetrachloro!0\2!dithietane was oxidized withtrichlorotriacetic acid "in dichloromethane at 9>C#\ and the 0!oxide thus obtained further oxidizedto the corresponding 0\2!dioxide ð72CB0512Ł[ The latter compound is cleaved quantitatively todichlorosul_ne by means of vacuum pyrolysis at 379>C and 9[4 torr "mm Hg# "Scheme 2#[

Scheme 3

S

Cl

Cl

S

S

Cl

ClCl

Cl S

S

Cl

ClCl

Cl

O

O

OMeCO3H, CH2Cl2, 0 °C

51%

∆


"b# From thiophos`ene[ Thiophosgene!S!oxide was synthesized from thiophosgene in 21) yieldby oxidation with mcpba "Equation "3## ð58TL3350Ł[ It is obtained as a yellow liquid "b[p[ 23Ð25>Cat 14 torr "mm Hg##[

S

Cl

Cl

OS

Cl

ClPhCO3H, 0 °C

(4)

"c# From trichloromethanesulfenyl chloride[ Cl1C1SO was also obtained by hydrolysis oftrichloromethanesulfenyl chloride Cl2CSCl in ca[ 29) yield "slightly dependent on the reactionconditions# and was found to be a thermally unstable compound ð58CC767Ł[

"d# From allyl trichloromethyl sulfoxide[ Cl1C1SO was obtained in 38) yield by pyrolysis ofCl2CS"O#CH1CH1CH1 at 299Ð399>C ð75CB158Ł[

"iii# Dibromosul_ne Br1C1SO

Dibromosul_ne "a reddish liquid# was described for the _rst time by Schork and Sundermeyerð74CB0304Ł[ Tetrabromo!0\2!dithietane was oxidized with tri~uorotriacetic acid in dichloromethanein two steps to the corresponding 0\2!dioxide^ the pyrolysis of this 0\2!dioxide gave dibromosul_nein 69) yield "Scheme 3#[

S

Br

Br

S

S

Br

BrBr

Br S

S

Br

BrBr

Br

O

S

S

Br

BrBr

Br

O

O

O

Scheme 4

F3CCO3H, CH2Cl2, 0 °C

24.6%

F3CCO3H, 0 °C

44.7%

∆

The IR spectra of F1C1SO\ Cl1C1SO and FClC1SO "Section 5[06[0[1[3# were obtained at 09Ð14 K in an argon matrix on a CsI window ð75SA"A#0170Ł in order to di}erentiate the sulfoxides fromthe corresponding dihalocarbonyls and thiocarbonyl compound[ Characteristic vibrations are givenin Table 0 ð75SA"A#0170Ł[

Table 0 Characteristic frequencies of halocarbonyls\ thiocarbonyls\ and the correspondingsulfoxides "wavenumbers in cm−0#[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐX0X1C1S X0X1C1O X0X1C1SO

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐX0 � X1 � Cl 0029"nC0S# 0706"nC0O# 0058"nC0S#

674"nassCCl1# 726"nassCCl1# 835"nassCCl1#X0 � F\ X1 � Cl 0146"nC0S# 0757"nC0O# 0186\ 0135"nC0S#

0903"nC0F# 0984"nC0F# 0020\ 0034"nC0S#501"nC0Cl# 665"nC0Cl# 539"nC0Cl#<

0949\ 0971"nS0O#X0 � X1 � F 0243"nC0S# 0829"nC0O# 0262"nC0S#

0079"nassCF1# 0133"nassCF1# 0185"nassCF1#0007"nS0O#

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

5[06[0[1 Thiocarbonyl Halides with Two Dissimilar Halogens

5[06[0[1[0 Thiocarbonyl chloride ~uoride

"i# From dichloro~uoromethanesulfenyl chloride

Thiocarbonyl chloride ~uoride FClC1S "a yellow liquid boiling at 6>C# can be readily synthesizedfrom the sulfenyl chloride FCl1CSCl in 76) yield by reduction with tin and concentrated HClð48ZOB2681Ł[


"ii# Other methods

FClC1S was obtained as a by!product of the F1C1S synthesis via the pyrolysis of 1!chloro!1\3\3!tri~uoro!0\2!dithietane and could be readily separated from F1C1S by distillationð54JOC0264Ł[ Also\ benzenethiosulfonic acid S!dichloro~uoromethyl ester can be thermally decom!posed "at 069Ð149>C# "Equation "4##^ the yields obtained were satisfactory ð72HOU"E3#396Ł[

(5)–C6H5SO2Cl

S

F

Cl

PhO2SS F

ClCl

5[06[0[1[1 Thiocarbonyl bromide ~uoride

Thiocarbonyl bromide ~uoride\ FBrC1S\ a yellow liquid boiling at 3Ð7>C and 099 torr "mmHg#\ can be obtained in 23) yield from thiocarbonyl chloride ~uoride by halogen exchange withBBr2 at 59Ð54>C ð70CB718Ł[ FBrC1S spontaneously decomposes at room temperature[

5[06[0[1[2 Thiocarbonyl bromide chloride

Thiocarbonyl chloride bromide\ ClBrC1S\ a red liquid boiling at 36>C and 79 torr "mm Hg#\has been obtained from thiophosgene in 03) yield by halogen exchange with BBr2 ð65CB2321\70CB718Ł[

5[06[0[1[3 Sulfoxides of thiocarbonyl halides "sul_nes# with two dissimilar halogens

"i# Chloro~uorosul_ne ClFC1SO

Chloro~uorosul_ne was synthesized from 1\3!dichloro!1\3!di~uoro!0\2!dithietane by oxidationwith tri~uoroperacetic acid at −09>C to the 0\2!dioxide^ pyrolysis at 349>C of the latter compoundgives ClFC1SO nearly quantitatively[ This could not be isolated but was identi_ed by on!line massspectrometry and photoelectron spectroscopy\ respectively "Scheme 4# ð76CB0388\ 77JFC"28#218Ł[ Theisomerism of the chloro~uorodithietanes was studied by 08F NMR spectroscopy and x!ray structureanalysis ð76CB0388Ł[ The two isomers of chloro~uorosul_ne "Equation "5## were identi_ed by IRand PE spectroscopy and\ synthetically\ by cycloaddition to 0\2!cyclopentadiene ð76CB0388Ł[

Scheme 5

S

F

Cl

S

S

F

ClCl

F S

S

F

ClCl

F

O

O

OMeCO3H, –10 °C ∆

S

Cl

F OS

F

Cl O

(6)

ClFC1SO was also obtained by pyrolysis of FCl1CS"O#CH1CH1CH1 at 299Ð399>C^ it wasidenti_ed by means of mass spectrometry ð75CB158Ł[


5[06[0[2 Thiocarbonyl Halides with One Halogen and one Other Heteroatom Function

5[06[0[2[0 Fluorothioformates ROC"F#1S

Thiocarbonyl chloride ~uoride reacts with alcohols at low temperature but without any solventleading selectively to the alkyl ~uorothioformates ROC"F#1S "R�Me\ Et\ Pri\ Ph# ð48ZOB2681Ł[

5[06[0[2[1 Chlorothioformates ROC"Cl#1S

"i# From phenols and naphthols

Phenols and naphthols readily react with thiophosgene in the presence of a base to give arylchlorothioformates in good yield "Equation "6## ð51JOC3498\ 54CB1952\ 54LA"570#53\ 56AG"E#170\72HOU"E3#396Ł[ Aryl chlorothioformates "in addition to those given in ð72HOU"E3#396Ł# which weresynthesized in this way are listed in Table 1[ Hydrocarbons and chlorohydrocarbons were used assolvents[ Phenyl chlorothioformate is a yellow liquid boiling at 80>C and 09 torr "mm Hg#ð48ZOB2681Ł[ In a number of cases\ the aryl chlorothioformates were not isolated but used for thesynthesis of thiocarbonic acid derivatives ð70JA821\ 71EUP51723\ 72JA3948\ 76USP3643961Ł[ In some casesthiophosgene was produced directly in the reaction mixture "see above# "a# by chlorination ofCS1 ð74JAP51019247\ 89JAP92119062Ł from which the corresponding phenyl chlorothioformates wereobtained in 82Ð85) yield^ "b# by reduction of CCl2CSCl ð74JAP50118759\ 74JAP50118750\ 77JAP1998747Ł\the aryl chlorothioformates being obtained in 52) yield and the corresponding naphthyl derivativesin 63) yield^ and "c# by reducing CCl2SH with SO1 ð75GEP2505998Ł[

OH S

Cl

Cl

+O

S

Cl

(7)NaOH

–HCl

Table 1 Aryl chlorothioformates synthesized from thiophosgene and phenols or napthols[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐAryl0OH Base Yield Ref[

")#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐPhenol NaOH:H1O 84[9 80JAP92107225

80JAP92082648m!tert!butyl!phenol NaOH:H1O 82JAP94947889m!tert!butyl!phenol NaOH:H1O 87[8 77JAP90290543m!R0!p!R!phenol NaOH:H1O 72JAP59044041R0 � halogen^ R � alkyl − 14\5\6\7!tetrahydro!naphthol!1 NaOH:H1O 78[8 89JAP939554554\5\6\7!tetrahydro!naphthol!1 NaOH:H1O 79[8 89JAP93017152

89JAP9492150576JAP90091947

4\5\6\7!tetrahydro!naphthol!1 NaOH:H1O:Na1S1O3 70[9 76JAP90964351C5Cl40OH NaOH 88[9a 74SUL501\3\5!Trimethyl!phenol NaOH 70[9b 74SUL501\5!di!OMe0C5H2ONa 37c 89CL72*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐa Colorless solid^ m[p[ 097Ð001 >C[ b Oily product^ m[p[ 39Ð32 >C[ c In THF at 9 >C[

The esters ROC"Cl#1S "R�succinimido\ phthalimido\ norborn!4!ene!1\2!dicarboximido#proved to be useful reagents for introducing the thiocarbonyl group into organic compoundsð77EGP162721Ł[

"ii# From alcohols\ alcoholates\ and alkoxytrimethylsilanes

Propargyl chlorothioformate "a light yellow liquid boiling at 30>C and 7 torr "mm Hg# wasobtained "41) yield# as above from propargyl alcohol and thiophosgene with sodium hydride asthe base "Equation "7## ð81AG"E#755Ł^ the corresponding allene\ CH11C1CHCH1OC"Cl#1S\ could


not be isolated owing to spontaneous ð2\2Ł!sigmatropic rearrangement to CH11C"CH1CH1#SC"Cl#1O ð81AG"E#755Ł[

S

Cl

ClOH

O Cl

S

(8)+NaH

Alkyl chlorothioformates have been synthesized in two di}erent ways[ The _rst is the reaction ofthiophosgene with a potassium alkoxide in the corresponding alcohol ROH "or in tetrahydrofuran#between −54>C and 04>C ð75S659Ł[ EtOC"Cl#1S was prepared from thiophosgene in 82) yieldwhen the reaction mixture was kept for 0 h at −59>C in ethanol and tetrachloromethane "Equation"8## and other alkyl chlorothioformates were similarly isolated in high yield[ When sodium alkoxidesRONa "R�Et\ Prn# were used\ the corresponding alkyl chlorothioformates "R�Et\ Prn# wereobtained in approximately 49) yield ð73ZAAC"497#025Ł[ As an alternative\ the reaction ofalkoxytrimethylsilanes with thiophosgene\ which does not require basic media\ was tried ð75S659Ł^the yields\ were\ however\ no higher than 24) "Equation "09##[

S

Cl

Cl

(9)+EtOK

–KCl, –EtOHROH

RO Cl

S

EtO

Cl

Ssolv./cat. at 80 °C

Cl

Cl

SEtO-TMS + (10)

The second method is the chlorolysis of bis"alkoxythiocarbonyl# disul_des with Cl1 or SOCl1ð46GEP0907943\ 54CB1948\ 72JOC3649Ł[ However\ the alkyl chlorothioformates are obtained in loweryield than from the _rst method\ the reagents must be very clean\ and the products are di.cult topurify by distillation "Equation "00## ð75S659Ł[

S S

SS

RO OR

Cl

S

RO (11)Cl2

2

5[06[0[2[2 Fluorodithioformates RSC"F#1S

"i# From chlorodithioformates

The alkyl ~uorodithioformates RSC"F#1S "R�Et\ Prn# have been synthesized in yields of 39)and 59)\ respectively\ from the corresponding chlorodithioformates with KF under solidÐliquidphase!transfer catalysis conditions "07!crown!5 in acetonitrile under argon#^ spectroscopic data wasobtained ð73ZAAC"498#56Ł[

"ii# Other methods

The reaction of thiols RSH "R�Me\ Et# with FClC1S\ but without any solvent\ is an alternativefor the synthesis of alkyl ~uorodithioformates ð48ZOB2681Ł[ Per~uoromethyl ~uorodithioformateCF2SC"F#1S can be synthesized from tri~uoromethyl thiol CF2SH with anhydrous NH2 ð44JCS2760Ł"yield 39)# or with KF ð57CB1598Ł "yield 47)# as HF acceptors[ The yield increases to ca[ 85) ifFClC1S and Hg"SCF2#1 are used at room temperature ð61CB719Ł^ CF2SC"F#1S is obtained in thisway as a yellow liquid boiling at 32>C ð57CB1598Ł and it can be readily converted into CF2SC"Cl#1S"yield 76)# with BCl2 ð65CB0865Ł[


5[06[0[2[3 Chlorodithioformates RSC"Cl#1S

"i# From thiols

Alkyl chlorodithioformates RSC"Cl#1S "R�Et\ Prn\ Pri\ Bun# were synthesized in yields of 44)to 69) from the corresponding thiols RSH and thiophosgene in dry CS1 at room temperatureð73ZAAC"497#025Ł[ The compounds could be readily stored at −19>C under argon^ spectroscopicdata was obtained[

"ii# From carbon monosul_de

The insertion of carbon monosul_de into the SCl bond of sulfenyl chlorides was used for thesynthesis of alkyl and aryl chlorodithioformates[ However\ the production of CS needs special careand equipment ð63IC0667Ł[ In this way\ trichloromethyl chlorodithioformate "an orange oil boilingat 87Ð099>C and 03 torr "mm Hg## was obtained from trichloromethanesulfenyl chloride in 64)yield "Equation "01## ð73JOC2743Ł and phenyl chlorodithioformate PhSC"Cl#1S from phenyl chloro!dithioformate in 62) yield ð73JA152Ł[ Chlorodithioformates which have been prepared by thismethod are S1C"Cl#SSC"Cl#1S "49) yield#\ Cl2CSCCl1SC"Cl#1S "38)# ð75SUL192Ł\ and a num!ber of other RSSC"Cl#1S derivatives ð75ACS"B#598Ł] R�COMe\ an orange oil "49)#\ R�COCl\a dark red oil boiling at 44Ð45>C and 9[93 torr "mm Hg# "42)#\ R�CCl2\ an orange oil boiling at67Ð79>C and 9[93 torr "mm Hg# "46)#\ and R�C1Cl4\ an orange oil boiling at 097Ð098>C and9[92 torr "mm Hg# "08)# ð75ACS"B#598Ł[

Cl

S

Cl3CS (12)Cl3C SCl + CS

S1C"Cl#CH1CH1SC"Cl#1S "a light yellow oil\ 27) yield# and 1\4!bis"chlorothiocarbonylthio#!0\2\3!thiadiazole "yellow needles melting at 58>C\ 099)# were obtained in the same way "Equation"02## ð80SUL032Ł[

NN

SClS SCl

NN

SS SCl

S

Cl

S

(13)2 CS

"iii# Other methods

Methyl chlorodithioformate MeSC"Cl#1S was obtained as the major product from"MeS#1C"Cl#SCl "with H1O\ 47)^ with aq[ KI\ 44)^ with MeSH\ 36)#\ from MeSCCl1SSMe "withH1O\ 70)^ with aq[ KI\ 61)^ with MeSH\ 59)# and from MeSCCl1SCl "with MeSH\ 25)#\respectively ð73SUL130Ł[

Alkali metal chlorodithioformates MSC"Cl#1S were prepared from the alkali metal chlorides"yields] M�Na\ 34)\ K\ 12)\ Rb\ 24)\ and Cs\ 20)# and CS1 in the presence of NaOH pelletsð72ZAAC"491#6Ł[ Ethyl chlorodithioformate EtSC"Cl#1S was obtained from KSC"Cl#1S and EtIbut only in 01) yield ð72ZAAC"491#6Ł[ Diazocarbonyl compounds can also give chlorodithioformateswith thiophosgene "Equation "03## ð53LA"563#013Ł[

S

Cl

Cl

+ 2

O

N2+

MeO

–

O

S

MeOCCl3

S

Cl

(14)–N2

"iv# Speci_c methods for aryl chlorodithioformates

The reaction of pentachlorobenzenesulfenyl chloride and sodium trithiocarbonate gave thepentachlorophenyl chlorodithioformate in 35) yield "Equation "04## ð74T4034Ł[


C6Cl5S SCl

ClCl (15)C6Cl5

S Cl

SNa2CS3

–2Cl–

Aryl chlorodithioformates were also obtained by the reaction of arenediazonium chlorides withCS1 under Sandmeyer conditions "copper powder or Cu"I#Cl at room temperature# "Equation "05##ð68ZC178Ł and\ in the usual manner\ from thiophosgene and arenethiols "Equation "06## ð74SUL50Ł[This last method gave 3!nitrobenzenethio! ð62CB0376Ł and 1!naphthalenethio! derivativesð64JCS"P1#805Ł[ Penta~uorobenzenethiocarbonic acid chloride was obtained "59)# by Haas andKempf ð73T3852Ł from bis"penta~uorobenzenethio#mercury and thiophosgene "Equation "07##[

N N Cl– + CS2

+ CuCl

XX

S

S

Cl

(16)

S

Cl

Cl

ArSH + S

ArS

Cl

(17)NaOH, CHCl3

–HCl

(18)S

Cl

Cl

Hg(SC6F5)2 + S

S

Clpentane, 12 h

c. 60% C6F5

2 + HgCl2

5[06[0[2[4 Bromodithioformates RSC"Br#1S

"i# From thiols

Alkyl bromodithioformates RSC"Br#1S were obtained in 20) yield "R�Et# and 33) yield"R�Prn# by treating the corresponding thiol RSH with Br1C1S in ether at room temperatureunder argon[ The deep red liquids could be stored at −19>C under argon ð73ZAAC"498#50Ł^ spec!troscopic data was obtained[

"ii# Other methods

Tri~uoromethyl bromodithioformate F2CSC"Br#1S\ a red liquid boiling at 56>C and 049 torr"mm Hg#\ was obtained in 72) yield from F2CSC"F#1S by halogen exchange with BBr2 at 24Ð39>C^ IR\ 08F NMR\ UV\ and MS data was obtained ð65CB2321Ł[

5[06[0[2[5 Fluoroselenothioformates RSeC"F#1S

Tri~uoromethyl ~uoroselenothioformate F2CSeC"F#1S\ a liquid boiling at 46Ð47>C\ was pre!pared from Hg"SeCF2#1 and FClC1S at −67>C^ the 08F chemical shifts "25[2 and −096[5 ppm#\the IR and MS data of the compound were measured ð65ZAAC"316#003Ł[

5[06[0[2[6 Chloroselenothioformates RSeC"Cl#1S

"i# From alkaneselenols

In a similar way to the corresponding alkyl chlorodithioformates\ the selenoesters RSeC"Cl#1S"R�Et\ Prn\ yellow viscous oils# were synthesized from the corresponding alkaneselenols andthiophosgene in dry CS1 as the solvent at room temperature in yields of 52Ð65) ð73ZAAC"498#50Ł[


"ii# Other methods

F2CSeC"Cl#1S was synthesized from F2CSeC"F#1S in 86) yield by halogen exchange withBCl2 ð65ZAAC"316#003Ł[

5[06[0[2[7 Bromoselenothioformates RSeC"Br#1S

F2CSeC"Cl#1S\ a liquid boiling at 43>C and 49 torr "mm Hg#\ was synthesized photochemically"UV irradiation for 3 h# from F2CSeBr in 40) yield and by halogen exchange with BBr2 fromF2CSeC"F#1S at 39>C in 63) yield ð75ZN"B#302Ł[

5[06[0[2[8 Sul_nes derived from CF2SeC"Cl#1S and CF2SeC"Br#1S

Fockenberg and Haas ð75ZN"B#302Ł obtained the S!oxides of CF2SeC"Cl#1S and CF2SeC"Br#1S\respectively\ by oxidation with mcpba[ CF2SeC"Cl#1SO\ a yellow liquid boiling at 36>C and 09torr "mm Hg#\ was obtained in 45) yield and CF2SeC"Br#1SO\ a yellow liquid boiling at 59>Cand 09 torr "mm Hg#\ in 14) yield[

5[06[0[2[09 Thiocarbamoyl ~uorides R1NC"F#1S

N\N!Diethylthiocarbamoyl ~uoride Et1NC"F#1S was obtained from diethylamine and thio!carbonyl chloride ~uoride in 34) yield ð52CJC0532\ 53LA"489#012\ 69LA"622#084\ 69LA"624#047\ 64LA0914Ł[N\N!Dimethylthiocarbamoyl ~uoride Me1NC"F#1S was also prepared by treating CF11CFR"R�F\ Cl\ CF2# with tetramethylthiuramide sul_de at 029Ð024>C ð70URP793523Ł[ N!"Fluo!rothiocarbonyl#imidosulfuryl di~uoride F1S1NC"F#1S was synthesized by reaction of Si"NCS#3with SF3 ð66MIP42425Ł[

5[06[0[2[00 Thiocarbamoyl chlorides R1NC"Cl#1S

"i# From secondary amines and related compounds

Thiocarbamoyl chlorides can be synthesized from thiophosgene and secondary amines "Equation"08## ð52CJC0532\ 53LA"489#012\ 69LA"624#047\ 64LA0914Ł[ Data published after 0879 is given in Table 2[In two cases ð74JAP50122551\ 74JAP50122552Ł\ thiophosgene\ which is added to aromatic amines\ wasproduced directly in the reaction mixture from trichloromethyl thiol and SO1 ð74JAP50122551Łor NaHSO2 ð74JAP50122552Ł[ Higher yields were obtained by replacing secondary amines withtrimethylsilylamines "Equation "19## ð79T428Ł and the chlorothiocarbamates produced in this wayproved easier to purify[ The TMS derivative RN"TMS#C"Cl#1S was also obtained ð75ZOB0436Ł[

S

Cl

Cl S

Cl

N

R2

R1

HN

R2

R1

(19)+–HCl

(20)S

Cl

Cl S

Cl

N

R2

R1

TMSN

R2

R1

+–TMS-Cl

Triphenylphosphine N!trimethylsilylimide and triphenylphosphiniminium chloride were similarlyadded to thiophosgene "Scheme 5# ð76UKZ284Ł[


Table 2 Chlorothiocarbamates as synthesized from secondary amines or amides and thiophosgene[

NMeO N

Me

Cl

S

Chlorothiocarbamate Solvent m.p. Yield(%)

Ref.

dry etherO N

S

Cl170 °C 62.5 80CB1898

pat. 83JAP60056958

N

N

R2

Cl

S

R1 = lower alkylR2 = halogen, lower alkyl, lower alkoxy

ether 85EGP256705

88EGP273832THF/benzene

R1

62–64 °C

NN

S

Cl

(succinimido, phthalimido and norborn-5-ene-2,3-dicarboximido analogues have also been synthesized)

N,N'-Me,Ph–C(Cl)=S SO2/CCl3SH/CCl4/KI 45.1

N

O

O

S

Cl

85JAP61233662

NaHSO3/CCl3SH/CCl4/KI 30 85JAP61233663

colorless crystals

Ph3P N–TMS

Ph3P NH2+ Cl–

SCl

Cl

Ph3P N

Cl

S

b.p. 182–184 °C

Scheme 6

"ii# From tetraalkylthiuramide disul_des

Another generally used method for the preparation of thiocarbamoyl chlorides is the chlorinationof tetraalkylthiuramide disul_des "Table 3 and Equation "10##[ Chlorine ð78JAP2919145\ 81MI 506!90Ł\SO1Cl1 ð72JOC0338\ 77ZOB0378\ 78IZV898\ 89SC1658Ł and S1Cl1 ð78EUP244467Ł have been used as thechlorinating agent[ N\N!Dimethylthiocarbamoyl chloride was also synthesized from the monosul_deby reaction with phosgene "Equation "11## ð81MI 506!91Ł[

(21)

S

Cl

R2N

S S

SS

R2N NR2 2Cl2

(22)S

Cl

Me2N2S

S

Me2N NMe2

OCl

Cl

S


Table 3 Chlorothiocarbamates synthesized by chlorination of thiuramide disul_des[

S

Me2N Cl

S

Me2N Cl

S

Me2N Cl

S

Me2N Cl

S

Me2N Cl

S

Et2N Cl

Chlorothiocarbamate

NMe

Cl

S

Chlorination b.p. (°C)

Yield(%)

Ref.

SO2Cl2 96/17 torr 83.2 89IZV90988ZOB1489

SO2Cl2 94 83JOC1449

SO2Cl2 43 (m.p.) 97 90S2769

S2Cl2 99 89EUP355578

Cl2 92 92MI-617-01

SO2Cl2 70/13 torr 87 89IZV90988ZOB1489

Cl2 pat. 89JAP03020256

"iii# From thioformamides

The third synthetic method\ which is a general one for thiocarbamoyl chlorides\ is the chlorinationof thioformamides "Equation "12## ð72HOU"E3#396Ł[ SCl1 ð69LA"622#084\ 78CB002Ł\ Cl1 ð69LA"622#084Łand SO1Cl1 have been used as the chlorinating agent[ The thioformamides can be synthesized fromthe corresponding formamides with Lawesson|s reagent "Scheme 6# ð74JAP51003855Ł[

(23)

S

Hal

N

R2

R1Hal2

S

N

R2

R1

+ HHal

HCO2H/(MeCO)2OLawesson's

reagent

NMeO NMe

H

NMeO NMe

O

NMeO NMe

SCl

SO2Cl2/Et3N, CCl4NMeO N

Me

S

Scheme 7

"iv# Other methods

N\N!Dimethylthiocarbamoyl chloride was obtained as a by!product in the synthesis of alkyl iso!cyanates RN1C1O from RNHC"OR?#1S and Cl1C1N¦Me1Cl− ð81ZOR596Ł[ The stable gold


chloride complexes ClAuS1C"Cl#NMe1 and Cl2AuS1C"Cl#NMe1 have been isolated and char!acterized ð81POL782Ł[

"v# Methods for thiocarbazic acid chlorides "R01NNR1C"Cl#1S#

Thiocarbazic acid chlorides R0R1NN"R2#C"Cl#1S were prepared from the corresponding tri!alkylhydrazines and thiophosgene ð61CB1743\ 80AP"213#806Ł "Table 4 and Equation "13##[ Thiocarbazicacid chlorides were employed for the thiocarbazoylation of thiazine!1!ones and thiazolidine!1!onesð80LA394Ł[

Table 4 Thiacarbazic acid chlorides\ R0R1N0N"R2#0C"Cl#1S\ obtained from thiophosgeneand the corresponding trialkyl hydrazine[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR0 R1 R2 m[p[ Yield Ref[

")#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐMe Me Me 53Ð54 >C 58 61CB1743

morpholino Me 82 >C 43 80AP"213#806piperidino Me 30Ð31 >C 02 80AP"213#806

Me Me cyclohexano 29 >C 18 80AP"213#806*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

NN

R2

R1 H

R3S

Cl

Cl+ NN

R2

R1

R3

(24)

S

ClCH2Cl2, –30 °C to –15 °C

–HCl

5[06[0[2[01 Thiocarbamoyl bromides R1NC"Br#1S

Thiocarbamoyl bromides can be synthesized from the corresponding thioformamides by reactionwith bromine "Equation "12## ð69LA"622#084\ 61LA"644#034Ł[ For example\ MePhNC"Br#1S wasformed in 67) yield and EtPhNC"Br#1S in 72) yield[

5[06[1 FUNCTIONS CONTAINING AT LEAST ONE CHALCOGEN FUNCTION "AND NOHALOGEN#

5[06[1[0 Thionocarbonates "O\O!Diesters of Thiocarbonic Acid#

The direct reaction of alcohols and phenols with thiocarbonylating agents usually leads tothionocarbonates in good yield ð72HOU"E3#319Ł[ Thiophosgene and chlorothionoformates are mostoften used for thiocarbonylation^ several other reagents are used in speci_c cases[

"i# From thiophos`ene

In these reactions thiophosgene is allowed to react with a hydroxy compound in the presence ofa base "Equation "14##^ bases used include potassium carbonate ð58JOC2900Ł\ pyridine ð44JA1368\51JOC3498\ 79CB649Ł and 3!dimethylaminopyridine "dmap# ð71TL0868\ 72TL754Ł[ 0\1!Diols "Equation"15## ð71TL0868Ł and enols also react easily ð79CB649\ 72HOU"E3#319Ł[

(25)S

Cl

Cl

+base

2ROH S

RO

RO

S

Cl

Cl

+ SO

O

Ph

PhOH

OHPh

Ph

(26)dmap

95%

430At Least One Chalco`en

The above method is successful with 1!~uoroalcohols\ an example being the formation of bis"1!~uoro!1\1!dinitroethyl# thionocarbonate "Equation "16##^ it is unsuitable for nitroalcohols such as1\1!dinitropropanol and 1\1\1!trinitroethanol ð72HOU"E3#319\ 72JCED020Ł[

S

Cl

Cl

+HO–O2N

OH

FO2N

O2N

O

FO2N

S

O

O2N

FO2N

(27)2

"ii# From chlorothionoformates

This is the most general method for the preparation of mixed thionocarbonates ð72HOU"E3#319Ł[After protection of the 2! and 4!hydroxyl groups of methyl shikimate\ the 3!hydroxyl group can betransformed into a thionocarbonate by reaction with phenyl chlorothionoformate in the presenceof an equivalent amount of dmap "Equation "17## ð74TL3830Ł[ Similarly the 1?!hydroxy groupof 0!"2?\4?!O!"0\0\2\2!tetraisopropyldisiloxane!0\2!diyl#!b!D!ribofuranosyl#!0H!benzimidazole wastransformed into a thionocarbonate by reaction with dmap and p!tolyl chlorothionoformate "Equa!tion "18## ð76HCA027Ł[

S

PhO

Cl+

CO2Me

O-TBDMS

OH

TBDMS-O

dmap

CO2Me

O-TBDMS

O

TBDMS-O

S

OPh

(28)

S

4-MeC6H4O

Cl+

dmapO

OH

O

OSiPri

2

Pri2Si

O

N

N

O

O

O

OSiPri

2

Pri2Si

O

N

N

S

4-MeC6H4O

(29)

Sometimes a hydroxy derivative is metallated before treatment with an aryl "or alkyl# chloro!thionoformate^ for example\ by adding methyllithium and then ClC"1S#OPh to a solution of 0!O!benzyl!1\2!isopropylidene!L!lyxose in THF at −67>C\ the corresponding thionocarbonate wasobtained in 89) yield "Equation "29## ð74T3968Ł[

S

PhO

Cl

+

OHO

OBn

OO

MeLi, –78 °C

90%

OO

OBn

OO

PhO

S(30)

The reaction of pyranosides which do not possess cis!vicinal hydroxyl groups "e[g[ Me a!D!glc\Me b!D!xyl# with dibutyltin oxide and then with phenyl chlorothionoformate gives mono!thionocarbonates in good yield "Scheme 7# ð75CPB329Ł[ They\ in turn\ can be used for preparing thedeoxy compounds[ Pyranosides with cis!vicinal hydroxyl groups "e[g[ Me a!D!gal\ Me!b!D!ara# givecyclic thionocarbonates instead "Scheme 7#[

The reaction of a sulfone with butyllithium and then with an aldehyde at −39>C gives the lithiumsalt of a b!hydroxysulfone\ which can be used in situ for the synthesis of the correspondingthionocarbonate "Scheme 8# ð80TL1692Ł[ When diethyl di~uoromethylphosphonate is metallated


OH

OH OSn

O

Bu

Bu

O

OS

PhO Cl

S

OH

OH

OH

O OPh

S

Scheme 8

Bu2SnO

i, Ac2O, py

ii, Bu3SnH

deoxycompounds

with lithium diisopropylamide "LDA# in THF at −67>C and then reacted with a series of aldehydes\intermediate alkoxy adducts are obtained which give thionocarbonates in 60Ð89) yield with phenylchlorothionoformate "Equation "20## ð81TL0728Ł[ These thionocarbonates can then be used for thesynthesis of 0\0!di~uoroalkylphosphonates[

SO2Ph( )7


ii, RCHO, THF, –40 °C R

LiO SO2Ph

n-C7H15THF, –40 °C

4-FC6H4O Cl

S

R

O SO2Ph

n-C7H15

4-FC6H4O

S

Scheme 9

O

(EtO)2P F

F

O

(EtO)2PR

O

F F

S

OPh i, LDA, THF, –78 °C ii, RCHO, THF, –78 °C

iii, PhOCSCl, –78 °C(31)

Diol monothionocarbonates can be prepared as illustrated in Scheme 09[ 4!Oxopentyl phenylthionocarbonate ð80CPB0548\ 81TL1432Ł and 4!oxohexyl phenyl thionocarbonate ð81T8322Ł were pre!pared in the usual manner by treating the respective hydroxy compound with phenyl chloro!thionoformate[

R2

R1 R3

M

+ R4O OPh

O

S

( )4 R2

R1 R3

OR4

OHOPh

S( )4

R4OH

O

( )4

R2

R1 R3

MgBr

+

M = Li or MgBr

R2

R1 R3

OHR4

OH

( )4

R4 = H or Me

PhO Cl

S

Scheme 10

Very often\ the thionocarbonate group serves as a reactive intermediate or as a protective group^further examples of their formation from chlorothionoformates are given in Table 5[


Table 5 Further examples of thionocarbonates prepared by treating a hydroxy compound with achlorothionoformate[

S

MeO OMe

S

MeO Cl

S

EtO OEt

S

MeO OEt

S

EtO Cl

S

EtO Cl

S

PhO ClOMe

O OPh

S

O

O

O

S

PhO ClO OPh

S

Thionocarbonate

OO

O O

OMe

Chlorothionoformate Base Yield(%)

OPh

S

PhO

S

Ref.

72MeONa 83JOC4750

EtONa 40–46

S

PhO Cl

28

83JOC4750

MeONa

O

TBDMS-O

O

CN

83JOC4750

pyridine

OPh

84 88S226

pyridine 62

S

PhO Cl

43

91T121

pyridine

S

PhO Cl

89

91T6381

dmap

O

OPh

Ph

S

91JCS(P1)787

pyridine 92 92JOC6803

S

"iii# From thiocarbonylbis"azoles#

Thiocarbonylbis"azoles# react with two alcohol molecules or with diols forming acyclic or cyclicthionocarbonates\ respectively ð72HOU"E3#319Ł[ Thiocarbonyldiimidazole is most often used but0\0?!thiocarbonylbis"0\1\3!triazole# can also serve as the thiocarbonylating reagent ð72HOU"E3#319Ł[The latter proved to be very e}ective in preparing thionocarbonates from 1\1!dinitropropanol andfrom 1\1!di~uoro!1!nitroethanol[ The same approach can also be applied to the preparation ofunsymmetrical thionocarbonates "Scheme 00# ð72JCED020Ł[

An example of the formation of a thionocarbonate from a 0\1!diol and thiocarbonyldiimidazoleis shown in Equation "21#[ Several cyclic thionocarbonates were prepared from various 0\1!diolsand thiocarbonyldiimidazole in order to be used as initiators for radical!based cyclization reactionsð76TL4862Ł[ Catechol has also been used as a diol with thiocarbonyldiimidazole\ the thionocarbonate"0\2!benzoxadiole!1!thione# being formed in 71) yield ð77JOC1152Ł[ Mixed thionocarbonates havebeen prepared by the successive displacement of imidazole from thiocarbonyldiimidazole by twodi}erent alcohols ð81JOC5792Ł[


OHO2N

FO2N N N

NN N

N

S

O N NN

S

O2N

FO2N

pyridine, CH2Cl2 F3CCH2OH

O O

S

Scheme 11

O2N

FO2N

+

CF3

N NN N

S

+O

HOOH

OO

OO

O

S

(32)toluene, heat

72%

"iv# Other methods

Several cyclic thionocarbonates have been prepared by cyclization reactions^ two examples areshown in Equations "22# and "23# ð81CPB1168\ 82JOC1783Ł[ The reaction shown in Equation "23#\ andthe substitution process shown in Equation "24# ð81T5772Ł\ involve intermediate thioacyl radicals[By adding NaSH to a stirred mixture of methyl 1!O!methyl!b!L!arabinopyranoside and Viehe|s salt\methyl 1!O!methyl!2\3!O!thiocarbonyl!b!L!arabinopyranoside was isolated in 62) yield "Equation"25## ð71AJC0698Ł^ other diols were similarly converted into thionocarbonates[ An interesting routeto diaryl thionocarbonates proceeds via CuI complexes which react with carbon disul_de "Scheme01# ð77TL716Ł[

(33)EtO OPh

OH

S

( )4

O

O

S

+ PhOLi(TMS)2NLi, THF, RT, <5 min

76%

OHO

HO

O

O SMe

S

O

O

O

O O

S

(34)

HBu3SnH, AIBN, toluene, reflux

15%

OR

O Im

S

OR

O OMe

S

Bu3SnOMe, AIBN, toluene(35)

(36)O

OH

HO

MeOOMe

+ Me2N

Cl

Cl

+Cl–

O

O

O

MeOOMe

SNaSH


2CuCl + 4Et3N + 2NaOArO

[Et3N]2CuO

Cu[NEt3]2

Ar

Ar

CS2

40–98% ArO OAr

S+ Cu2S

Scheme 12

5[06[1[1 Dithiocarbonates "O\S!Diesters of Dithiocarbonic Acid#

Dithiocarbonic acid itself is unstable and decomposes spontaneously to H1S and COS[ However\its O!alkyl esters "xanthates# and their salts are relatively stable[

5[06[1[1[0 Salts of O!alkyl esters of dithiocarbonic acid

The potassium salts can be easily prepared from alcohols\ carbon disul_de and KOH using theappropriate alcohol as the solvent "Equation "26## ð59CB2945\ 66S762\ 72HOU"E3#319Ł[ These salts arevery often used to synthesize other derivatives of dithiocarbonic acids[ For example\ the reaction of2!"1!hydroxyethyl#! or 2!"2!hydroxypropyl#benzothiazolin!1!ones with potassium hydroxide andexcess carbon disul_de a}orded the corresponding dithiocarbonates "Scheme 02# ð77JHC0590Ł whichwere converted by aqueous ammonium persulfate to the corresponding disul_des or by chloro!alkanes to the S!alkyl derivatives[

ROH + CS2 + KOHRO S– K+

S+ H2O (37)

N

SO

OH

N

SO

O

S– K+

S

N

SO

O

SRS

N

SO

O

( )n

SS

( )n

+ CS2 + KOH

( )n

( )n

2

(NH4)2S2O8

RX

Scheme 13

5[06[1[1[1 O\S!Diesters of dithiocarbonic acids

"i# From salts of O!esters of dithiocarbonic acids

A salt M¦−SC"1S#OR "M�K or Na# can be converted into the corresponding O\S!diester byreaction with a chloroalkane or a similar reagent[ This is exempli_ed in Scheme 02^ further examplesare shown in Equations "27# and "28#[ By heating equimolar amounts of 1!chloromethylpyridine or1!chloromethylquinoline with potassium O!ethyl dithiocarbonate for 1 h the correspondingdithiocarbonates were obtained "Equation "27## ð78JPR328Ł[ Similarly\ the reaction of 2!chloro!


methylbenzothiazolin!1!thione with sodium O!alkyl dithiocarbonates "alkyl�Me\ Et# gave thecorresponding esters "Equation "28## ð78JHC0134\ 78JPR328Ł[ The preparation of 30 compounds ofthe type "EtOC"S#SCH1C5H3#1Z "Z�"CH1#0Ð5\ O\ S or SO1# from potassium O!ethyl dithiocarbonateand the corresponding chloro compound has been described ð89MI 506!92Ł[ The reaction of bromo!triphenylmethane with potassium O!ethyl dithiocarbonate in various conditions a}ords O!ethylS!triphenylmethyl dithiocarbonate in 68Ð83) yield ð89JCS"P0#1998Ł[ S!Methyl O!trimethylsilyldithiocarbonate was obtained "27)# from sodium O!trimethylsilyl dithiocarbonate and chloro!methane ð73ZAAC"404#071Ł[ The corresponding S!ethyl derivative was obtained similarly in 30)yield with iodoethane[

R Cl +K+ –S OEt

S

R S OEt

S(38) + KCl

R = 2-pyridyl, 2-quinolyl

(39)+Na+ –S OR

SN

SS

Cl

N

SS

S

ROS

+ NaCl

Protected glycosyl bromides and chlorides can be converted into the corresponding S!glycosyl O!ethyl dithiocarbonates with complete anomeric inversion in high yield ð80TL6342\ 81MI 506!93Ł^ anexample ð81MI 506!93Ł is shown in Equation "39#[

OAcHN

AcO

CO2Me

XAcO

OAcOAc

OAcHN

AcO

S

CO2MeAcO

OAcOAc

SOEt

K+ –S OEt

S+ + KX (40)

a!Haloketones and a!haloketoximes undergo displacement easily[ For example\ the reaction of1!chlorocyclopentanone with potassium O!isopropyl dithiocarbonate in acetone led to the formationof the corresponding dithiocarbonate ð82H"24#66Ł\ and 2!bromo!4!methylhexan!1!one reacted withpotassium O!ethyl dithiocarbonate in acetone to give the dithiocarbonate in 75) yield ð76JHC470Ł[Chloroacetaldehyde reacts with potassium O!ethyldithiocarbonate in an analogous way to give thedithiocarbonate in 54) yield ð81HCA896Ł[ There are many other examples of displacement of halidefrom a!halocarbonyl compounds ð71JIC771\ 73MI 506!90\ 74JIC053\ 75MI 506!93\ 77MI 506!90Ł[ Sodium O!methyl dithiocarbonate and a!chloroacetophenone oxime reacted to give the displacement product"as a mixture of syn and anti isomers# in 76) yield ð76S238Ł[ This was converted into 2!phenyl!3H!0\4\1!oxathiazine!5!thione by heating with tosyl isocyanate "Scheme 03#[ Related reactions of a!haloketoximes have been described ð74TL4832Ł[

Na+ –S OMe

S+

ClPh

NOH

87%MeO S

Ph

S

NOH

TsNCO S

ON

S

Ph

Scheme 14

Carboxylic acid chlorides react readily with potassium O!alkyl dithiocarbonates[ Acetyl chloridereacts with potassium O!ethyl and O!methyl dithiocarbonate to give the corresponding anhydridesMeCOSC"1S#OR in high yield ð70LA0133Ł[ Similar reactions of 1!furoyl chloride ð74MI 506!92Ł andof phthaloyl chloride "Equation "30## ð76JIC083Ł have been described[ Alkyl chloroformates can beused to prepare anhydrides of dithiocarbonic acids ð67JOC1829Ł[ Thus\ O!butyl S!ethoxycarbonyldithiocarbonate was prepared by slow addition of potassium O!butyl dithiocarbonate to an excessof ethyl chloroformate in acetone at 9>C ð72JCS"P0#1530Ł[ Phthaloylglycyl chloride reacted withpotassium O!alkyl dithiocarbonates to give the corresponding O!alkyl S!phthaloylglycyl dithio!carbonates[ Irradiation of the latter in benzene with a mercury lamp gave the corresponding alkyl


dithiocarbonates "Scheme 04# ð74IJC"B#574Ł[ Analogous reactions\ involving the extrusion of COSfrom dithiocarbonic anhydrides\ have been reported ð78TL3256Ł[

(41)K+ –S OR

S+ 2

Cl

Cl

O

O

O

O

ClCl

O

O

SS OR

S

RO

S

K+ –S OR

SN

O

O

Cl

O

N

O

O

S

O

S

OR+

N

O

O

S

OR

S

hν, C6H6

Scheme 15

An alcohol can be converted to a dithiocarbonate by allowing it to react with phosgene andpotassium O!ethyl dithiocarbonate[ The products have been used as condensing agents for thepreparation of peptides ð74KPS733Ł[ When irradiated with visible light\ these compounds give thecorresponding S!alkyl dithiocarbonates "Scheme 05# ð89JA1923Ł[ The radical intermediates in thesereactions can also undergo cyclization\ as shown in Scheme 06[ Irradiation of S!4!hexenyloxy O!ethyl dithiocarbonate converted it smoothly in re~uxing heptane into S!cyclopentylmethyl O!ethyldithiocarbonate whereas S!2!butenyloxy O!ethyl dithiocarbonate gave a lactone[

Scheme 16

K+ –S OEt

S

ROH +Cl Cl

O

RO Cl

O

RO S

O

OEt

S hν

RS OEt

S

Scheme 17

O S OEt( )n

O Shν, n = 3

87%

hν, n = 1

84%S OEt

S

S OEt

S

OO

Several other types of activated halides have been shown to react with O!alkyldithiocarbonatesalts[ 1!Chloro!3\4!dihydroimidazole reacts with two moles of potassium O!alkyl dithiocarbonatesgiving the corresponding diesters ðROC"1S#Ł1S and imidazoline!1!thione ð81JCS"P0#36Ł[ Dis!placement of chloride from 0!chloro!0\2\2!triphenylallene by potassium O!ethyl dithiocarbonatehas also been reported ð78BCJ856Ł[ The reaction of triphenyltelluronium chloride with the equivalentamount of sodium O!alkyl dithiocarbonate gives the corresponding triphenyltelluronium dithio!carbonate "Equation "31##[ The same product can be obtained by reacting a triphenyltelluroniumalkoxide with carbon disul_de[ The reaction of freshly prepared dimethyltellurium diiodide with asodium O!alkyl dithiocarbonate leads to dimethyltellurium bis"O!alkyl dithiocarbonates# "Equation"32##\ which can also be obtained by inserting carbon disul_de into dimethyltellurium bis"alkoxides#ð74ZAAC"414#016Ł[ S!"Alkoxycarbonyl# O!alkyl dithiocarbonates have been prepared by the additionof a solution of a potassium O!alkyl dithiocarbonate to that of an O!alkyl chlorothiocarbonate"Equation "33## ð79AQ072\ 72JCS"P0#1530Ł[


(42)Ph3TeCl +Na+ –S

S

OR Ph3TeS

S

OR+ NaCl

Na+ –S

S

OR(43)Me2TeI2 + Te

SS

MeMe

RO

S

OR

S+ 2NaI2

K+ –S

S

OR2

+ KClS

S

OR2R1O

S+

R1O

S

Cl(44)

Bis"methoxythiocarbonyl#sulfanes have been prepared by a variety of di}erent methods as shownin Scheme 07 ð76ZAAC"441#070Ł[ Several analogous preparations have been reported ð75JOC0755Ł[Methoxydichloromethanesulfenyl chloride\ when added to a suspension of potassium O!methyldithiocarbonate in CDCl2 at 4>C\ gave the dithiocarbonate which underwent a further displacementreaction with N!methylaniline "Scheme 08# ð89JOC0364Ł[ ðMethoxy"thiocarbonyl#Ł"chloro!carbonyl#disulfane\ MeOC"1S#S1COCl\ is obtained "30)#\ together with bisðmethoxy"thiocarbonyl#Łsulfane\ when ClSCOCl is added to a suspension of potassium O!methyl dithio!carbonate in chloroform ð75JOC0755Ł[

O

OMeClS

S OMeMeO

S S

S OMeSMeO

S

S

S OMeMeO

S

SS

S

S OMeSMeO

S

SS

(0.5 mol.)

80%

I2

SCl2S2Cl2S

K+ –S OMe

85%

93%97%

Scheme 18

SCl

Cl

MeO

ClS

K+ –S OMe+ MeO S

S OMe

S

ClCl

PhNHMe

39% S

S OMeN

Me

Ph

Scheme 19

Salts of O!alkyl dithiocarbonates can act as nucleophiles towards a variety of reagents other thanhalides[ Methoxythiocarbonyl methylsulfane can be synthesized by the reaction of potassium O!methyl dithiocarbonate with the S!methyl ester of methanethiosulfonic acid "Equation "34##ð76ZAAC"449#098Ł[ In basic conditions\ and in the presence of excess KSC"1S#OMe\ a furtherreaction can occur leading to the formation of a symmetrical disulfane[ When potassium O!isopropyldithiocarbonate reacts with "Z#!3!phenylbut!2!enyl methanesulfonate in the presence of a phasetransfer catalyst O!isopropyl "Z#!S!3!phenylbut!2!enyl dithiocarbonate is obtained "Equation "35##ð77JCS"P0#0406Ł[

S

K+ –S OMe+MeSO2SMe

S

S OMeMeS + MeSO2K (45)


(46)S

K+ –S OPri

+ + MeSO3K

Ph

OSO2Me

Bu4N+ Cl–

Ph

S S

OPri

A mixture of 2!O!acetyl!1!azido!3!"benzyloxycarbonyl#amino!1\3\5!trideoxy!D!galactopyranosylnitrate and the minor talopyranoside was obtained by treating a D!galactal with sodium azide andcerium"IV# nitrate in acetonitrile at −14>C ð81MI 506!94Ł[ A reaction of the above mixture withpotassium O!ethyl dithiocarbonate in acetonitrile in turn gave O!ethyl S!"2!O!acetyl!1!azido!3!"benzyloxycarbonyl#amino!1\3\5!trideoxy!b!D!galactopyranosyl# dithiocarbonate "Scheme 19#ð81MI 506!94Ł[ Several similar reaction sequences have been reported ð77LA64\ 80T4038\ 82HCA884Ł[

O

ZHN

AcO

N3

ONO2O

ZHN

AcO ONO2

N3+

S

K+ –S OEt

O

ZHN

AcO

N3

O

ZHN

AcO

N3

+S SOEt

S

OEt

S

NaN3, (NH4)2Ce(NO3)6

71%

OZHN

AcO

Scheme 20

58%

The addition of V[ harveyi oxidoreductase "NADH oxidized by ribo~avin# to an anaerobicsolution of potassium O!ethyl dithiocarbonate\ 00!deoxydaunomycin\ and NADH led to two dithio!carbonates "6S and 6R# in an 74 ] 04 ratio "Equation "36## ð72JA6076Ł[ The cyclization shown inEquation "37# is initiated by nucleophilic opening of the three!membered ring by potassium O!ethyldithiocarbonate ð77ZOR006Ł[

O

OOMe OH OR

OH

O

S

OH

O

S

OH

O

OEt

S

OEt

S

S

OEtK+ –S++

87%(47)

7-(R)7-(S) 85:15R = daunosamine

S

OEtK+ –SN

N N

N

O

O

Me

Me

X

S

+reflux

N

N N

N

O

O

Me

Me

S

S OEt

S

(48)

X = Cl, Br

"ii# From carbon disul_de

It is possible to prepare O\S!dialkyl dithiocarbonates directly from alcohols by reaction with abase\ carbon disul_de and a haloalkane[ This is mechanistically equivalent to using salts of O!estersof dithiocarbonic acids "5[06[1[1[1"i##\ but experimentally more convenient\ and the procedure has


been widely used[ In a typical procedure\ the sodium salt of the alcohol is produced by its reactionwith sodium hydride and a catalytic amount of imidazole in THF^ carbon disul_de and a haloalkaneare then added sequentially[ An example is shown in Equation "38# ð81JA3000Ł^ many others\encompassing a wide range of primary alcohols ð71JOC021\ 78CC0154\ 80JOC1738\ 81JOC5792Ł\ secondaryalcohols ð68JA5005\ 70CC645\ 70JCS"P0#1252\ 71HCA260\ 71YGK241\ 72JOC3649\ 76CC0117\ 77CAR"070#142\89TL3820\ 80T010\ 80T5270\ 81TL4150\ 82CAR"131#170\ 82CAR"135#008\ 82JOC1783\ 82JOC2687Ł\ tertiary alcoholsð82TL1622Ł and phenols ð75T1218Ł\ have been described[

(49)

O2S

NC

OH

O2S

NC

OS

SMe i, NaH ii, CS2iii, MeI

61%

Sometimes butyllithium is used in place of sodium hydride for the preparation of dithiocarbonatesdirectly from alcohols[ An example is shown in Equation "49# ð74T3968Ł^ other examples have beendescribed ð76BCJ0742\ 77M016Ł[ Phase!transfer catalysts have also been used with aqueous sodiumhydroxide as the base ð77M016\ 78SC436Ł[

(50)

O

OO

HO OBnO

OO

O OBn

MeS

S

i, BuLi ii, CS2iii, MeI

88%

An extension of the methodology involves the generation of a carbanion using butyllithium andits aldol addition to an aldehyde^ the lithium salt of the aldehyde then reacts further with carbondisul_de and iodomethane ð77TL5014\ 80TL1692Ł[ An example of the reaction sequence is shown inScheme 10 ð80TL1692Ł[

SO2Ph( )6

i, BuLi

ii, RCHO R

LiO SO2Ph

n-C7H15

i, CS2

ii, MeIR

O SO2Ph

n-C7H15

S

MeS

Scheme 21

By treating carboxylic esters with lithium diisopropylamide "LDA# at 9>C\ lithium enolates weregenerated[ The latter were treated with carbon disul_de followed by a haloalkane to produce O!"0!alkoxy!1\1!dialkylvinyl# S!alkyl dithiocarbonates in very good yield "Scheme 11# ð78CC573\78JOC4592Ł[

OR3

R2

R1

O

OR3

R2

R1

OLi

OR3

R2

R1

O

SLi

S

OR3

R2

R1

O

SR4

S

Scheme 22

LDA, 0 °C CS2, –78 °C R4X

"iii# From thiocarbonyl chlorides

O\S!Dialkyl dithiocarbonates can be prepared by the displacement of chloride from alkoxy!thiocarbonyl chlorides by thiolate anions[ For example\ S!ethyl O!methyl dithiocarbonate wasobtained by adding sodium ethanethiolate to a solution of methoxythiocarbonyl chloride in etherat a rate to maintain a mild re~ux "Equation "40## ð72JOC3649Ł[ Silver salts have also been used forpreparations of this type ð75JOC3377Ł\ and imidazolides ROC"1S#Im "Im�0!imidazolyl# have beenused in place of alkoxythiocarbonyl chlorides ð75T1218Ł[


Cl

S

MeO+ NaSEt

SEt

S

MeO(51)+ NaCl

S!"Alkoxycarbonyl# O!alkyl dithiocarbonates have been prepared in high yield by the additionof a solution of a potassium O!alkyl monothiocarbonate to that of an O!alkyl chlorothiocarbonatein aqueous acetone "Equation "41## ð74PS"14#80Ł[ In the presence of a phase transfer catalyst andaqueous sodium thiosulfate\ methoxythiocarbonyl chloride gives bis"methoxythiocarbonyl# sul_de"63)# "Equation "42## ð72JOC3649Ł[

Cl

S

R1O+ KCl+

OR2

S

K+ –S S

S

R1O OR2

O(52)

Cl

S

MeO+ 2NaCl + SO3+

S

S

MeO OMe2 Na2S2O3

Bu4NI

74%(53)

S

An alternative procedure is to displace chloride from dithiocarbonyl chlorides such asPhSC"1S#Cl with alkoxide anions ð80T010Ł[

"iv# By radical addition to alkenes

Examples of intramolecular addition of radicals ROC"1S#S= to carbonÐcarbon double bondshave already been illustrated in Scheme 06[ Intermolecular radical addition reactions have also beenreported ð77CC297\ 78H"17#060Ł^ two examples are shown in Equations "43# and "44#[

Ph S OMe

S+ N

O

O

MeN

O

O

Me

S

Ph

MeO S

(54)hν

40%

But S OEt

S+

hν

45%O(55)SO2Ph

But

S

SO2Ph

OEt

S

"v# From other dithiocarbonates

The radical reaction of bromoalkanes with O!ethyl triphenyltin dithiocarbonate was initiated bytributyltin hydride and 1\1?!azobisisobutyronitrile "AIBN# or by visible light[ Dithiocarbonates wereobtained in good yield ð81JA6898Ł[ The reaction sequence is illustrated in Scheme 12 for a radicalwhich undergoes cyclization before capture^ the sequence depends on the ability of triphenyltinradicals to add reversibly to dithiocarbonates[

Ph3SnS OEt

S

Ph3SnS OEt

SR*

S OEt

SR*R•

O

Br

O O O

H

H

S

S

OEt

•R*• + + Ph3Sn•

Ph3SnS OEt

S

88%

Scheme 23

e.g.

Bu3SnH, AIBN or hνPh3Sn•

RBrR• + Ph3SnBr


O!Ethyl S!"1!hydroxy!3!oxo!3!phenylbutyl# dithiocarbonate and related esters were prepared byallowing lithium enolates of ketones to react with O!ethyl S!"1!oxoethyl# dithiocarbonateð81HCA896Ł[ An example is shown in Equation "45#[

Pr O

Et

Pr O

Et

S

S

OEt

OH

i, LiN(TMS)2 ii, ZnCl2

S S

OEtO

(56)

iii,

5[06[1[2 Derivatives of Trithiocarbonic Acid

Trithiocarbonic acid\ "HS#1C1S\ can be generated from barium trithiocarbonate by reaction withdilute HCl at 9>C ð52ZAAC"210#032Ł[ It is\ however\ stable only at −67>C^ otherwise it decomposes tohydrogen sul_de and carbon disul_de[ Salts of trithiocarbonic acid are obtained by the reaction ofcarbon disul_de with metal sul_des or metal hydrogen sul_des ð72HOU"E3#319Ł[ A 0\4!diazabi!cycloð4[3[9Łundec!4!ene "dbu# salt was obtained by heating a mixture of water\ CS1\ and dbu inmolar ratios 1 ] 2 ] 3 ð75CE200\ 76NKK0397Ł[

5[06[1[2[0 Salts of monoesters of trithiocarbonic acid

The reaction of aliphatic or aromatic thiolate salts with carbon disul_de gives salts of themonoesters of trithiocarbonic acid "Equation "46## ð69JA2231\ 69MI 506!90\ 61JA0452\ 79JOC064\ 82POL02Ł[In a few cases lithium salts have been generated by fragmentation of 0\2!dithiole derivativesð70TL4084\ 71BCJ228Ł^ an example ð70TL4084Ł is shown in Scheme 13[

S • S + RS– M+RS S– M+

S(57)

SS

S

S

S

S

SS

S

S

S

S

–

Li+

–

Li+

2BuLi

Li+ –S SS S– Li+

S

S

+ 2C2H4

Scheme 24

5[06[1[2[1 Diesters of trithiocarbonic acid

"i# From thiophos`ene

Diesters of trithiocarbonic acid can be prepared in very good yield from thiophosgene and saltsof thiols and thiophenols "Equation "47## ð50JOC3936\ 72HOU"E3#319Ł[ The reaction of thiophosgenewith dithiolates gives cyclic trithiocarbonic acid esters "Equation "48## ð66CC559\ 72HOU"E3#319Ł[


+ 2RS– M+S

ClCl+ 2MCl

S

SRRS(58)

+S

ClCl+ 2MCl

R

M+ –S S– M+

R

S

S S

R R

(59)

"ii# From S!esters of dithiocarbonic acid chloride

The starting acid chlorides can be isolated as intermediates from the reaction of thiophosgenewith thiols or thiophenols ð72HOU"E3#319Ł^ they form mixed esters when allowed to react furtherwith another alkanethiol or thiophenol "Equation "59## ð50JOC3936\ 60CC203Ł[

(60)+ R2S– M+S

ClR1S+ MCl

S

SR2R1S

"iii# From salts of monoesters of trithiocarbonic acid

The salts are excellent nucleophiles\ and they are alkylated by haloalkanes and a range of otheralkylating agents ð72HOU"E3#319Ł[ The reaction can also be conveniently carried out by generatingthe salt in situ from a thiol\ carbon disul_de\ and a base ð75S783Ł[ Phase transfer catalysts have beenused to achieve one!pot conversions of thiols to dithiocarbonates ð76BCJ324Ł[

An example of the alkylation reaction "which was used as a step in a penem synthesis# isshown in Equation "50# ð70TL2374Ł[ There are several other similar examples of the preparation oftrithiocarbonates derived from azetidinones ð70CPB2047\ 76H"14#012\ 81JOC3241Ł[ A reaction of pot!assium 0\1!ethanebis"trithiocarbonate# with HCl gave 0\1!ethanebis"trithiocarbonic acid#\HSCSSCH1CH1SCSSH[ Further reaction with iodoalkanes gave RSC"1S#SCH1CH1SC"1S#SR"R�Me\ 75)^ R�Et\ 71)# ð74ZAAC"429#090Ł[ An example of the use of a leaving group otherthan a halide is provided by the reaction of potassium S!methyl trithiocarbonate with the S!methyl ester of methanethiosulfonic acid\ MeSO1SMe\ which gave methyl methylthiothiocarbonyldisulfane\ MeSC"1S#S1Me ð76ZAAC"449#098Ł[

S

SEtK+ –S+

N

Cl

O O

MeO2C

O

O

OCl3C

N

S

O O

MeO2C

O

O

OCl3C

S

SEt(61)+ KCl

Many electrophiles other than alkylating agents have also been used\ and some of these areillustrated in Scheme 14[ Reactions of the salts are shown with 1!chloro!2\4!dinitropyridineð70JHC0470Ł\ methyl chlorodithioformate\ iodine\ sulfur monochloride\ and sulfur dichlorideð76ZAAC"434#014\ 76ZAAC"443#061Ł and trichloromethanesulfenyl chloride ð74T4034Ł[ The reaction ofRPCl1 or R1PCl "R�Me\ Pri\ Ph# with NaSCSSR0 "R0�Et\ Pri# gave RP"SCSSR0#1 andR1PSCSSR0\ respectively ð77PS"24#82Ł[ Triphenyltellurium chloride reacted with sodium S!alkyltrithiocarbonates giving the corresponding S!alkyl S!triphenyltellurium trithiocarbonates in highyield ð77ZAAC"445#078Ł[


S

RS S– M+

N

O2N NO2

S SBut

SS S

SCCl3

S

Ph

S SMe

S

SSMeS

S

S SMe

S

SS

SMeS

S

SMe

S

SMeS

S

S SMe

S

SMeS

S

N

O2N NO2

Cl

Scheme 25

R = But, M = Na

92%

ClSCCl3R = PhCH2, M = Na

81%

S

MeS ClI2

R = Me, M = K85%

S2Cl2R = Me, M = K

97%SCl2R = Me, M = K

86%

R = Me, M = K79%

"iv# From trithiocarbonate salts

Sodium\ potassium\ and barium salts of trithiocarbonic acid react with alkylating agents givingsymmetrical dialkyl trithiocarbonates "Equation "51## ð79CPB009\ 71BCJ0063\ 72HOU"E3#319Ł[ Theseesters were also synthesized in high yield in the presence of a phase transfer catalyst ð75S783\ 77S11\77SC0420Ł[ For example\ carbon disul_de and 22) aqueous sodium hydroxide were stirred together\and haloalkanes were then added in the presence of tetrabutylammonium hydrogensulfate "Scheme15# ð77SC0420Ł[ The dbu trithiocarbonate salt also reacts with alkylating agents to give dialkyltrithiocarbonates in good yields ð75CE200\ 76NKK0397Ł[ The method can be used to prepare cyclictrithiocarbonates^ for example\ cis!2\4!dibromocyclopentene reacted with sodium trithiocarbonatein DMF to give the cis!2\3!cyclopenteno!0\2!dithiolane!1!thione "Equation "52## ð82H"24#66Ł[

2RX +S

–S S–

S

RS SR+ 2X– (62)

S

Na+ –S S– Na+

S

RS SRS • S

Scheme 26

NaOH (aq.) i, Bu4NHSO4 (cat.)

ii, 2RX

(63)Na+ –S S– Na+

S+

Br

Br

S

SS + 2NaBr

58%

Other types of electrophile can be used to functionalize the trithiocarbonate salts[ For example\the reaction of sodium trithiocarbonate with trichloromethanesulfenyl chloride gave the crystalline"Cl2CS1#1CS\ which on oxidation gave the sul_ne "Cl2CS1#1CS1O ð73SUL74Ł[ The compounds"RS1#1C1S can be prepared by treating a sulfenyl chloride "R�CCl2\ CCl2CCl1\ CCl1FCCl1 orCClF1CCl1# with an excess of freshly prepared aqueous sodium trithiocarbonate in dichloromethane\or with anhydrous barium trithiocarbonate suspended in acetonitrile ð74T4034Ł[ Oxidation of thesecompounds with mcpba gave the sul_nes "Scheme 16#[

When thioureas are prepared by three!component reactions of amines\ carbon tetrachloride\ andsodium sul_de\ the reactions proceed exothermically in the presence of a phase!transfer catalystð72LA0728Ł[ Thiophosgene is an intermediate in this conversion\ and its phase!transfer catalyzedtransformation into carbon disul_de and trithiocarbonate can be demonstrated[ When the amine


RSClBaCS3 or Na2CS3 mcpbaRSS SSR

S

RSS SSR

SO

Scheme 27

was replaced by dibromomethane\ benzyl chloride or a\b!dibromostyrene\ the products included 0\2!dithietane!1!thione "4)#\ dibenzyl trithiocarbonate "34)#\ and 3!phenyl!0\2!dithiolane!1!thione"49)#\ respectively ð72LA0728Ł[ An analogous reaction\ in which 3!chloromethyl!0\2!dioxolane isthe electrophile\ has been reported ð80JPR028Ł[

"v# Methods leadin` to cyclic trithiocarbonates

Five!membered cyclic trithiocarbonates are accessible by a variety of routes ð54JA823\ 64JOC2941\65JOC515\ 70TL4084Ł and several of the general routes described above can be used "e[g[ those inEquations "48# and "52##[ The following are some speci_c methods[

Several cyclic trithiocarbonates have been prepared from the corresponding dithio!N\N!dimethyl!iminium salts by reaction with hydrogen sul_de or with sodium hydrogensul_de ð81CC0309\81KGS0006\ 82H"24#66Ł[ An example of the process is shown in Equation "53# ð82H"24#66Ł[ A di}erentroute to cyclic trithiocarbonates is shown in Equation "54#[ A suspension of tetraethylammoniumtetrathiooxalate in acetonitrile was stirred with carbon disul_de at ambient temperature until theformer had dissolved[ Chloromethane was then bubbled through the solution[ The precipitateobtained consisted of 64Ð89) of 3\4!bis"methylthio#!0\2!dithiole!1!thione and 09Ð14) of dimethyltrithiocarbonate ð75ACS"B#482Ł[

(64)S

SNMe2 BF4

–+

S

SS

H2S, –40 °C

86%

S

SS

MeS

MeSS– Et4N+S

S S– Et4N+ i, CS2

ii, MeCl+ S

MeS

MeS(65)

1!Pyridyl! and 1!quinolyl dithiocarbonates cyclocondense with carbon disul_de to yield 3\4!disubstituted 0\2!dithiole!1!thiones in 04 to 59) yield "Scheme 17# ð78JPR"220#328Ł[

R1 ClK+ –S OEt

S

S OEt

S

R1 S OEt

S

R1

S––S

S

SR1

R2S

S

R2I+

i, NaH

ii, CS2

R1 = 2-pyridyl, 2-quinolyl

Scheme 28

5[06[1[3 Derivatives of Thiocarbamic Acid

Thiocarbamic acid has the structure H1NC"1S#OH[ The free acids R0R1NC"1S#OH decomposeto COS and the corresponding amine when their preparation is attempted\ but their salts can beprepared by treating COS with amines in the presence of an alkali metal hydroxide[ Alkylation oracylation of these salts usually gives S!esters of thiocarbamic acid ð70S511\ 70ZAAC"370#015Ł[ The O!esters are isolable but when heated those bearing a dialkylamino group can isomerize to S!estersð55JOC2879\ 58JOC2593\ 62JOC1095Ł^ those with a monoalkylamino function can decompose to iso!thiocyanates and alcohols ð72HOU"E3#319Ł[


5[06[1[3[0 O!Esters of thiocarbamic acids

"i# From O!alkyl or O!aryl chlorothioformates

The reaction of O!alkyl or O!aryl chlorothioformates with amines is a general method for thepreparation of O!esters of thiocarbamic acids ð72HOU"E3#319Ł^ the following are examples of themethod[

N\N\O!Trimethyl thiocarbamate was prepared from dimethylamine and O!methyl chloro!thioformate "Equation "55## ð76CB876Ł[ 0\1\2\3!Tetrahydro!1!"methoxythiocarbonyl#!b!carboline!2!carboxylic acid was obtained by adding an ethereal solution of O!methyl chlorothioformate andaqueous sodium hydroxide to an aqueous solution of sodium 0\1\2\3!tetrahydro!b!carboline!2!carboxylate "Equation "56## ð76CPB1739Ł[ 3!"Nitrophenylamino#aniline reacted with O!phenylchlorothioformate and pyridine in acetone to give the corresponding O!phenyl thiocarbamateð77MI 506!91Ł[ The amino group of 3!cyano!2!methylthiopyrazol!4!amine was similarly substitutedð81PHA140Ł[

MeO Cl

S+ 2Me2NH

MeO NMe2

S+ Me2N+H2 Cl– (66)

MeO Cl

S+

NH

NH

CO2Na

NH

N

CO2Na

OMe

S

(67)+ NaClNaOH

35%

The reaction of an O!aryl chlorothioformate "one equivalent# with an alkyl or aryl bis"tri!methylsilylamine# "three equivalents# in ether at room temperature gave the corresponding thi!ocarbamate in good yield "Scheme 18# ð74PS"10#180Ł[ If the chlorothioformates were used in excess\the products were the corresponding N!alkyl or N!aryl bis"O!arylthionocarbonates# "Scheme 18#[

ArO

S

Cl+ RN(TMS)2

ArO

S

NTMS

R

ArO

S

N

R

OAr

S

Scheme 29

"ii# From N\N!dialkylthiocarbamoyl chlorides

This general method is exempli_ed by the preparation of N\N!diethyl O!phenyl dithiocarbamatefrom phenol "Equation "57##[ A solution of phenol in DMF was poured into a suspension of sodiumhydride in DMF and stirred at 9>C[ After hydrogen evolution was over\ N\N!diethylthiocarbamoylchloride was added and the mixture was heated for 0 h at 79>C[ After separation\ 65) of N\N!diethyl O!phenyl thiocarbamate was obtained ð55JOC2879\ 81S001Ł[ Similar preparations have beenreported from N\N!dialkylcarbamoyl chlorides and the following] substituted phenols ð48JA603\80CPB0828Ł\ 0!naphthol ð81S001Ł\ 2!hydroxypyridine ð81S001Ł\ methyl 2!hydroxythiophene!1!carb!oxylate ð73S061Ł\ "R#!"¦#!0\0?!binaphthol ð82JOC0637Ł\ other binaphthols ð80PS"52#40Ł and calix!ð3Łarenes ð89CC0321Ł[

(68)Et2N Cl

S+ + NaCl

76%PhO– Na+

Et2N OPh

S

2!Methyl!1!ð"dimethylthiocarbamoyl#oxyŁ!2!methylcyclopent!1!en!0!one and related compounds


ð75JOC3630Ł can be prepared by adding lithium hydroxide solution at room temperature to a stirredsolution of the ketone in chloroform\ and then a solution of N\N!dimethylthiocarbamoyl chloridein chloroform "Equation "58## ð76JOC4529Ł[ Cyclohexane!0\1!diones have been used as the startingmaterials for similar preparations ð77JOC0009Ł[

(69)Me2N Cl

S+

HOO

OO

Me2N

S

The thiocarbamoyl chloride can be generated in situ and then reacted with the appropriate alcoholor phenol] an example of this approach is shown in Scheme 29 ð89OPP017Ł[

Cl2 2-naphthol

80%

N Cl

S

Ar

Me

N SS N

Ar

S

Ar

Me S

Me

N O

S

Ar

Me

Scheme 30

Ar = 3-MeC6H4

"iii# From N\N?!thiocarbonyldiimidazole and related compounds

A mild procedure for the functionalization of alcohols is to heat the alcohol with N\N?!thio!carbonyldiimidazole in a solvent such as dichloromethane or THF "Equation "69##[ This procedurewas used to convert several epoxyalcohols into the thiocarbonylimidazolides in high yieldð70JCS"P0#1252Ł\ and there are several other examples of similar procedures ð64JCS"P0#0463\ 74T3968\76JA598\ 81JOC5792\ 81T5772\ 81T7920\ 81TL4150Ł[

N NN N

S

N ORN

S

HN N++ ROH (70)

O\N!Dibenzyl N!methyl thiocarbamate was prepared by adding sodium hydride to a solution of0!"N!benzyl N!methyl thiocarbamoyl#imidazole and benzyl alcohol in acetonitrile "Equation "60##ð77JOC1152Ł[ 0!ð"Benzyloxy#thiocarbonylŁimidazole was obtained from N\N?!thiocarbonyl!diimidazole\ benzyl alcohol\ and sodium hydride^ this compound also gave O\N!dibenzyl N!methylthiocarbamate when benzylamine was added ð77JOC1152Ł[

N N N

S

N O

S

HN N++ PhCH2OH Ph

Me

Ph (71)Ph

Me

"iv# From aminoalcohols and carbon disul_de and related methods

Several fused tetrahydro!0\2!oxazine!1!thiones were prepared from aminoalcohols "as in theexample shown in Scheme 20# by cooling a solution of the aminoalcohol in aqueous potassiumhydroxide to 9>C\ and then mixing the solution with a solution of carbon disul_de in dioxane[Aqueous lead"II# nitrate was then added and lead sul_de precipitated[ The oxazine!1!thiones wereobtained by extraction with ethanol ð72T0718Ł[ An alternative procedure is to add thiophosgene toa solution of the aminoalcohol and triethylamine ð72T0718Ł[ There are other reports of the prep!


aration of a variety of oxazine!1!thiones from aminoalcohols by similar methods ð71H"08#0080\72JHC0070\ 73JHC0262\ 74S0038\ 74T0242\ 89MRC0934Ł[

O

N

H

H

R

SOH

NH2

OH

NHMe

i, KOH (aq.) ii, CS2iii, PbNO2

42% (R = H)

Cl2CS, Et3N

23% (R = Me)

Scheme 31

0\2\3!Oxadiazole!1!thiones were obtained by reacting the respective hydrazides with carbondisul_de in the presence of potassium hydroxide "Equation "61## ð82JMC0989\ 82JMC0791Ł[

R NHNH2

O+ S • S

KOH NN

OR S

H

(72)

"v# From isothiocyanates

The addition of alcohols to isothiocyanates "Equation "62## is a general method for the preparationof O!alkyl thiocarbamates^ many examples of the procedure have been reported ð72JHC0112\ 72ZOR81\73CCC0466\ 73ZOR1047\ 74JPR0996\ 74KGS228\ 74MI 506!90\ 74S312\ 75MI 506!91\ 76CCC0653\ 78CPB0138\78MI 506!90\ 89JHC396\ 89JHC532\ 89JOC4129\ 89MI 506!91\ 89ZOR0311\ 80S154\ 82OPP72\ 82TL2634Ł[ Othersinclude the preparation of the N!penta~uorosulfanyl derivative SF4NHC"1S#OMe "76)#ð73CB0696Ł and the reaction of hydroxypyridones with alkyl isothiocyanates ð76MI 506!91\ 80PJS311Ł[A cyclic trimeric isothiocyanato phosphazene reacts with alcohols "R�Me\ Et\ Pr\ Bu\ Pri# giving_rst "at 14>C# a species in which three of the six thiocyanato groups have reacted\ a highertemperature "55>C# being necessary to bring about reaction of all the isothiocyanato groups "Scheme21# ð80IC0665Ł[ Butadien!0!yl thiocyanate undergoes a DielsÐAlder reaction with dienophiles\ andthe cycloadducts were intercepted by reaction with ethanol "Equation "63## ð75HCA0787Ł[ Thehydroxyl group of ~uorenone oxime adds to benzoyl isothiocyanate to give the thiocarbamateð74CC0394Ł[ O\O!Dialkyl imidodicarbonothioates R0OC"1S#NHC"1S#OR1 can be obtained byreaction of O!alkyl carbonochlorodithioates R0OC"1S#Cl with sodium isothiocyanate and treat!ment of the resultant alkoxythiocarbonyl isothiocyanates with alcohols R1OH ð74S864Ł[

(73)+R1N • S R2OH N OR2

S

R1

H

(74)

Z

NH

EtO

SEtOH, 110 °C

Z+N

•S

ROH

25 °C

ROH

66 °C

N

PN

P

NP

NN

N

NN

N

•S

•S

• S

•

S

•

S

•SN

PN

P

NP

HNN

HN

NN

NH

•S

• S•S

S

O R

S

OR

S

RO

N

PN

P

NP

HN

HN

HN

HN

HN

NH

S

RO OR

S

SORRO

S

Scheme 32

OR

SS

RO


The reaction of phosgene with one or two equivalents of ammonium thiocyanate gives thio!carbonyl chloride thiocyanate "8)# or thiocarbonyl dithiocyanate "62)#\ respectively ð70CB0021Ł[The latter compound reacts with alcohols to give O!alkyl imidodi"thiocarbonic acids#\ðROC"1S#Ł1NH[ Carbonyl isocyanate isothiocyanate\ SCNC"1O#NCO can be obtained by con!densing carbonyl chloride isocyanate with ammonium thiocyanate ð70CB1953Ł[ This reacts furtherwith an alcohol giving O!alkyl "isothiocyanatocarbonyl# carbamates\ ROC"1O#NHC"1O#NCS[These can react further with a second equivalent of an alcohol "which can be the same alcohol or adi}erent one# to give the esters ROC"1O#NHC"1O#NHC"1S#OR ð70CB1953Ł[

"vi# From O!alkyl thiocarbamic acids and their salts

O!Methyl thiocarbamic acid\ MeOC"1S#NH1\ can be obtained in 56) yield by treating thecorresponding potassium salt in water with chloroacetic acid ð70ZAAC"370#015Ł[ O!Ethyl thio!carbamic acid\ EtOC"1S#NH1 was obtained "35Ð49)# from dry ammonium thiocyanate in ethanolat 01Ð04>C after adding sulfuric acid ð71CB0141Ł[ It reacts with oxalyl chloride giving a mixture ofethoxy"thiocarbonyl# isocyanate\ EtOC"1S#NCO and its dimer "Scheme 22#[ Ethoxy"thiocarbonyl#isocyanate reacts further with alcohols and amines as shown in Scheme 22 ð71CB0148Ł[

(COCl)2EtO NH2

S

EtO N

S

•O + N

S

N

O

OEt

S

OEtO

ROH R2NH

EtOHN OR

S O

EtOHN NR2

S O

Scheme 33

"vii# Other methods

O!Ethyl thiocarbamates were prepared by the reaction of potassium O!ethyl dithiocarbonate withamines ð78JOC1867Ł[ When N!arylbenzimidoyl chlorides were added to various potassium O!alkyldithiocarbonates\ O!alkyl esters of the corresponding N!aryl!N!thiobenzoyl thiocarbamic acidswere obtained "Equation "64## ð70ZC327Ł[ Other imidoyl chlorides reacted similarly ð74ZC108Ł[A rearrangement is also involved in the alkylation of some dithiocarbamates "Equation "65##ð77JCS"P0#702Ł[ Alkylation of the potassium salts K¦−SC"1S#O"CH1#nOC"1S#S− K¦ gave dialkylbis"dithiocarbonates#\ which on reaction with amines RNH1 gave the bis"thiocarbamates#RNHC"1S#O"CH1#nOC"1S#NHR ð71MI 506!92Ł[

Ph Cl

NAr+

S

K+ –S ORPh N OR

S S

Ar

(75)+ KCl

S

S N

O

Ph + PhCH2Cl

O

O

PhS

N

S

O

Ph

(76)base

96%

N\N!Dimethyl!N?!phenylthiourea\ PhNHC"1S#NMe1\ reacts with ethyl bromocyanoacetate togive O!ethyl N!phenylthiocarbamate\ EtOC"1S#NHPh ð71JCS"P0#542Ł[ The reaction of 1\2!dihydro!


5!methoxy!1!thioxo!3H!0\2\4!thiadiazine!3!one with dibenzylamine resulted in the formation of adithiocarbamate by ring cleavage "Equation "66## ð70CB1964Ł[

HN

S

N

O

S OMe

+ PhHN Ph N

HN OMe

O S

Ph

Ph (77)–HSCN

87%

Several routes to dithiocarbamates involve the displacement of sulfur functions by amino func!tions[ Some of these are illustrated in Equation "67# ð89ZC89Ł\ Equation "68# ð76CPB045Ł\ Equation"79# ð72JCS"P0#1900Ł\ and Equation "70# ð75JOC0755Ł[ The reaction of dithiocarbonate esters withN\N!dimethylhydrazine leads to mixtures of thionocarbamates and thionocarbazates whereasalkoxythiocarbonylimidazoles give cleanly the latter ð73JCS"P0#0994Ł[

(78)R1O S OEt

S O

R1O NHR2

SR2NH2+ + EtOH + COS

(79)RS OEt

SN

NH2 I–

base N– N

+

OEt

S

+ +

(80)EtO SMe

S+

93%H2NNH2

EtO NHNH2

S

(81)S OMe

S+

89%PhNHMe

MeO

S

MeO N

S

Ph

Me

5[06[1[4 Derivatives of Dithiocarbamic Acid

The parent compound\ dithiocarbamidic acid\ can be obtained as an unstable crystalline solidfrom the reaction of ammonium dithiocarbamate and concentrated HCl at 9>C[ Other dithio!carbamic acids\ R0R1NC"1S#SH\ are also unstable compounds which can be generated from theirsalts with HCl ðB!51MI 506!90\ B!66MI 506!90Ł^ they decompose to amines R0R1NH and carbon disul_deð72HOU"E3#319Ł[

5[06[1[4[0 Salts of dithiocarbamic acids

Alkylammonium dithiocarbamates are prepared from carbon disul_de and two moles of theamines in solvents such as acetone or ethanol ðB!51MI 506!91\ 68JINC0166\ 79ZC090\ 72HOU"E3#319Ł[When the reaction is carried out in aqueous sodium hydroxide or potassium hydroxide\ the sodiumor potassium dithiocarbamates are formed ð40RTC806\ 40RTC838\ 54JMC063Ł[ Formamide reacts withcarbon disul_de in the presence of sodium hydroxide to give sodium N!formyl dithiocarbamate\Na¦−SC"1S#NHCHO ð74ZAAC"411#034Ł[ The reaction of hydrazine hydrate with carbon disul_deand methanolic potassium hydroxide gives potassium dithiocarbazate\ K¦−SC"1S#NHNH1

ð74ZAAC"420#090Ł[ With a 1 ] 0 ratio of carbon disul_de to hydrazine\ the product is the salt1K¦−SC"1S#NHNHC"1S#S− ð74ZAAC"420#71Ł[ Carbon disul_de reacts with methylhydrazine atthe substituted nitrogen atom ð78S812Ł whereas it reacts with arylhydrazines at the unsubstitutednitrogen atom ð81CCC0588Ł[ Lithium dithiocarbamates were obtained from secondary amines bydeprotonation of the amine using butyllithium in THF at 9>C followed by the addition of carbon


disul_de in THF at 9>C ð80S526Ł[ This procedure is particularly useful with cyclic secondary aminessuch as indoline since the salt can be further deprotonated at C!1 by s!butyllithium ð83S872Ł andthis allows electrophiles to be introduced at C!1[

5[06[1[4[1 Esters of dithiocarbamic acids

"i# From dithiocarbamates

The S!alkylation of alkali metal or ammonium dithiocarbamates by haloalkanes and relatedcompounds is the most general method for the preparation of esters of N!alkyl or N!aryl dithio!carbamates "Equation "71##[ The method is fully documented in earlier reviews ðB!51MI 506!90\ B!51MI 506!91\ 72HOU"E3#319Ł\ and there are many more recent examples[ A wide range of electrophileshas been used^ these include haloalkanes\ alkyl nitrates\ a!haloketones\ a!haloesters\ activatedheteroaryl halides\ aromatic diazonium salts\ acyl halides\ and activated alkenes[ A selection ofexamples from the 0879s is given below[

(82)+ R3XS– M+R1R2N

S

SR3R1R2N

S+ MX

The standard method for S!methyl esters is the reaction of dithiocarbamate salts with iodo!methane ð71ZAAC"377#83Ł[ S!Alkyl esters\ "H1N#1C1NC"1S#SR\ of guanidinothioformic acid wereprepared from its potassium salt and iodoalkanes "e[g[\ R�Me\ 72)^ R�Bn\ 32)#ð71ZAAC"374#192Ł[ S!Alkyl!N!formyl!N!methyl dithiocarbamates\ OHCN"Me#C"1S#SR\ wereobtained from the potassium salt of the corresponding acid in an analogous mannerð74ZAAC"416#029Ł[ The S!alkyl esters\ S1CHNHC"1S#SR\ of N!thioformyl dithiocarbamic acidwere prepared by reaction of iodoalkanes with tetra!n!butyl N!thioformyl dithiocarbamateð74ZAAC"414#001Ł[ Several examples of the formation of dithiocarbamates from disaccharides bydisplacement of bromide have been described ð80CAR"105#160Ł^ one of these is shown in Equation"72#[ 1!Chloromethylquinoline and other halomethyl!substituted heterocycles have also been con!verted into dithiocarbamates by displacement of halide ð76BCJ0796\ 78JPR"220#328Ł[

NMe2Na+ –S

SOO

AcO

OOAcO

OAcOMe

BrO

OAcO

OOAcO

OAcOMe

S

+ NaBr

NMe2

S58%

(83)+

There are many examples of the displacement of halide from a!halocarbonyl compounds bydithiocarbamate anions[ These include reactions of 0!"chloroacetyl#piperidine ð70UKZ15Ł\ 1!"chloro!acetamido#benzothiazole ð71FES194Ł\ 1!"chloromethyl#benzimidazole ð74IJC"B#0187Ł\ and of severalchloroacetyl substituted heterocycles ð74MI 506!93\ 74IJC"B#479\ 75MI 506!91\ 76MI 506!90\ 78JIC59\81AF0342Ł[ The reaction of chloroacetonitrile with sodium N\N!dimethyl dithiocarbamate in thepresence of a phase!transfer catalyst\ tetrabutylammonium iodide\ has been reported ð77BCJ1192Ł[The reaction of a!bromocarboxylic acids with sodium or potassium N\N!dialkyl dithiocarbamate isillustrated in Equation "73# ð80JOC4573Ł[ The ester "−#!menthyl chloroacetate ð74MI 506!90Ł\ a!chloroalkylnitrosamines "RN"NO#CH1Cl# ð76LA472Ł\ and chloromethyl oximes ð76S238Ł have beenused in similar displacement reactions[ a!Haloketones undergo displacement of halide easilyð74H"12#2988Ł\ and some of the dithiocarbamates formed in this type of process have been reducedby baker|s yeast to chiral alcohols\ as illustrated in Scheme 23 ð77BCJ2194Ł[

CO2H

Br+

–S NMe2

S 73%S NMe2

S

CO2H

(84)+ Br–


Cl

O+

Na+ –S NMe2

SS

O

NMe2

S

S

OH

NMe2

S

88%

baker's yeast

91%, >96% ee

Scheme 34

Carbon electrophiles other than halides can be used] there are examples of the formation ofdithiocarbamates from epoxides ð73AP"206#0931Ł and from tosylates ð77S113\ 81JA09462Ł[ Dithio!carbamates can also be formed by conjugate addition reactions or by conjugate additionÐeliminationreactions with activated alkenes ð73MI 506!91Ł[ An example of conjugate addition followed bycyclization is illustrated in Scheme 24 ð80M0936Ł\ and related reactions of 3!benzylideneoxazoloneshave been described ð81S808Ł[ 3!Chloro!2!nitrocoumarin reacts with potassium N\N!dialkyl dithio!carbamates in acetone by displacement of the nitro group\ whereas chloride is displaced in thereaction with potassium N!phenyl dithiocarbamate "Scheme 25# ð81JHC272Ł[ Examples of additionÐelimination reactions of a\b!unsaturated sulfones ð70KGS896\ 73ZOR1003Ł include the preparation ofsulfolene derivatives "Equation "74## ð70KGS896Ł[

Ar

O

+HS

HN Ph

S

Ar

O

S N

S

H

PhN

S

Ar

S

Ph

Scheme 35

HCl, –5 °C 20 °C

Scheme 36

O

Cl

NO2

OO

Cl

S

OO

S

NO2

O

NR2

S

NHPh

SK+ –S NR2

S

K+ –S NHPh

S

–S NR2

SSO2

Cl

SO2

SNR2

S+ (85) + Cl–

Acid chlorides react readily with dithiocarbamate salts ð70LA0277\ 73MI 506!93\ 77ZOR1908Ł[ Aryl a!chlorooxime O!methanesulfonates also react to give isolable but unstable dithiocarbamates whichcan be cyclized to dithiazolium salts with ~uoroboric acid "Scheme 26# ð74CC0530Ł[ Acetylenereacts with amines and carbon disul_de to give either mono! or bis"dithiocarbamates# "Scheme 27#depending upon the temperature and the reaction conditions ð70ZOR1158Ł[

S!Aryl dithiocarbamates have been prepared from sodium dithiocarbamates and diaryliodoniumsalts "Equation "75## ð76JCS"P0#1648\ 76JOC3006Ł[

Na+ –S NR2

S

Cl Ar

NOSO2Me

SAr

NMeO2SO

NR2

S

SN

SAr NR2 BF4–

+HBF4

+

Scheme 37


H + R2NH + 2H S • S R2N S

S

S

NR2

SSR2N

S

Scheme 38

Ar2I+ X– +Na+ –S NR2

S

ArS NR2

S+ ArI + NaX (86)

There are several examples of the use of heteroatomic electrophiles for the substitution ofdithiocarbamate salts[ For example\ salts M¦−SC"1S#NMe1 react with iodine to give"SC"1S#NMe1#1 and with SCl1 and S1Cl1 to give the corresponding tri! and tetrasulfanes\ respectivelyð77ZAAC"445#030Ł[ Other iodine coupling reactions are reported ð74ZAAC"413#000\ 74ZAAC"416#014Ł[Reaction with MeSO1SMe gives MeS1C"1S#NMe1 ð76ZAAC"440#080Ł[ Substitution reactions usingphosphorus halides ð70ZOB429\ 71MI 506!91\ 72JIC795Ł and tellurium halides ð77JCS"D#1252Ł have alsobeen reported[ TMS esters are formed with TMS!Cl ð77JOC1152Ł[

"ii# From carbon disul_de

The reaction between amines and carbon disul_de to give dithiocarbamates was described in "i#above[ Procedures in which dithiocarbamate S!esters are made in one pot from carbon disul_de\ anamine\ and an electrophile are therefore not essentially di}erent from those already described[However\ examples of the procedure are given here since the method is experimentally convenient[

A typical procedure is described for the preparation of N!aryl S!methyl dithiocarbamates fromanilines ð70S850Ł[ The compounds were obtained by adding aqueous sodium hydroxide and carbondisul_de to a vigorously stirred solution of the aniline derivative in DMSO at room temperature[Iodomethane was then added a with ice cooling[ The mixture was poured into water\ and theprecipitated product was isolated and recrystallized from ethanol[ Similar procedures have beendescribed for N!aryl S!nonyl dithiocarbamates ð71JMC446Ł and for S!allyl N!aryl dithiocarbamatesð80S036Ł[ Other procedures have been described for the preparation of N\N\S!trialkyl dithio!carbamates ð73MI 506!92\ 77S664\ 80S526Ł and for the formation of dithiocarbamates from chloroaceticacid and carbon disul_de ð71MI 506!90Ł[

The reaction of sodium N!formyl dithiocarbamate\ Na¦−SC"1S#NHCHO\ obtained from for!mamide\ carbon disul_de and sodium hydride\ with iodomethane or iodoethane in ether gives therespective S!alkyl N!formyl dithiocarbamates ð74ZAAC"413#006Ł[ Acyl dithiocarbazatesRC"1O#NHNHC"1S#SR were prepared from acylhydrazines by reaction with carbon disul_deand aqueous potassium hydroxide\ followed by alkylation with an iodoalkane ð71JMC446Ł[Methylhydrazine has also often been used in this type of preparation ð61ICA00\ 67JINC340\ 77S589Ł[The reaction of methylhydrazine\ carbon disul_de and potassium hydroxide with 0\1!bis"bromo!methyl#benzene gave the bis"N!methyl dithiocarbazate# "Equation "76## ð80POL712Ł[ Dibromo!methane has been used as the electrophile in the formation of 0\0!bis"dithiocarbamates# ð80ANC0184Ł[

+ 2 S • SBr

Br+ 2MeNHNH2

KOH S

S

N(Me)NH2

S

N(Me)NH2

S

(87)+ 2KBr

A large number of heterocycles containing the NC"1S#S function are known\ and many of themare prepared using carbon disul_de[ A few representative examples are given below[

Reactions of b!lactones with dithiocarbamates\ generated in situ from amines and carbon disul_dein the presence of a base\ lead to 0\2!thiazine!1!thiones by way of intermediate dithiocarbamates


"Scheme 28# ð70AP"203#476\ 71AP"204#092\ 73AP"206#186\ 74AP"207#737\ 75AP"208#0953\ 78IJC"B#328Ł[ 0\2!Thia!zoline!1!thiones were prepared in high yield by the route shown in Equation "77# ð78M760Ł[

O

R2

R1 R4

R3

O

S • S R5HN SCO2

–

R3

R4

R1 R2S

N

S

O

R5

S

R4

R3

R2

R1+ R5NH2 +

Ac2O/H+base

Scheme 39

S • S+EtO2C N SEt

S

R1

i, NaOBut

ii, R2X

S

N

R2S

EtO2C S

R1

(88)

The oxidation by iodine of potassium N!methyl N!thioformyl dithiocarbamate\K¦−SC"1S#NMeC"1S#H\ obtained in 79) yield from N!methylthioformamide\ carbon disul_de\and potassium hydroxide at −04>C\ gives N!methyl!0\1\3!dithiazol!2\4!dithione "Equation "78##ð74ZAAC"417#057Ł[ Similarly\ 0\2\3!oxadiazol!1!ylmethyl N!aryl dithiocarbamates undergo oxidativecyclization with thionyl chloride or iodine to yield 4!aryl!0\2\3!oxadiazoloð2\1!dŁð0\2\3Łthiadiazine!5"4H#!thiones "Equation "89## ð78IJC"B#328Ł[ Various 0\2\3!thiadiazole!1"2H#!2!thiones have beenprepared from hydrazine derivatives and carbon disul_de ð82JMC0989\ 82JMC0791Ł[ 4!Phenyl!0\1\3!dithiazole!2!thione was obtained from its sodium salt formed from sodium hydride\ thiobenzamide\and carbon disul_de in dry pyridine after treating the latter with HCl ð74ZAAC"414#001Ł[ The reactionof a primary alkylamine and carbon disul_de with 0\3!dibromobutane!1\2!dione also results in theformation of a heterocycle\ 3\3?!bis"2!alkyl!3!hydroxy!thiazolidine!1!thione# ð78SUL012Ł[

(89)N S– K+

S

Me

S SS

NS S

Me

I2

32%

NN

OR S NHAr

S

I2 or SOCl2N

S

NN

OR

Ar

S(90)

Many heterocyclic amines have been functionalized on nitrogen by reaction in basic conditionswith carbon disul_de and an alkylating agent[ For example\ carbon disul_de was reacted with thelithium salt of imidazoline 1!thione in THF\ and iodomethane was then added to give S!methyl1!methylthio!3\4!dihydroimidazole!0!carbodithioate "Equation "80## ð70JCS"P0#1388\ 70S897Ł[ The re!action of 4!amino!0\1\3!triazoles with carbon disul_de "9[0 mole#\ potassium hydroxide "9[0 mole#\and alkylating agents results in substitution of either the exocyclic amino group or a ring nitrogenatom\ depending on the amount of base used ð89JHC0138Ł[ 1!Aminothiazole has similarly beenconverted into a dithiocarbamate ð70ZOR080Ł[ The reactions of pipecolic acid\ 0\1\2\3!tetra!hydroisoquinoline!2!carboxylic acid\ and 0\1\2\3!tetrahydro!b!carboline!2!carboxylic acid with car!bon disul_de in the presence of sodium hydroxide followed by alkylation with methyl iodide readilygave the corresponding dithiocarbamates ð76CPB1739Ł[

(91)+ S • S + 2MeIN

HN

S

– Li+79%

N

N SMe

S SMe

Carbon disul_de inserts into the P0N bonds of 1!dimethylamino! or 1!diethylamino!2!phenyl!0\2\1!oxazaphospholanes "Equation "81## ð70ZOB17Ł[ Analogous insertion reactions of carbon dis!ul_de into P0N bonds ð72ZOB674Ł and into As0N bonds ð78ZOB1419Ł have been reported[


Formamide reacts with carbon disul_de in the presence of sodium hydroxide to yield crude sodiumN!formyl dithiocarbamate\ NaSC"1S#NHCHO ð74ZAAC"11#034Ł[

+ S • SO

PNPh

NR2

94% (R = Me)86% (R = Et) O

PNPh

S NR2

S

(92)

Dithiocarbamic acids derived from amines and carbon disul_de add to vinyl ethers and thioethers"Equation "82## ð75ZOR1034\ 76ZC13Ł[ Additions to alkoxyallenes have also been reportedð89ZOR0253Ł[ Hydroxybenzyl dialkyldithiocarbamates were prepared in 34Ð78) yields from thecorresponding phenols by aminomethylation with formaldehyde and secondary amines followed bythiocarbamoylation with carbon disul_de ð75MI 506!92Ł[ Bis"dithiocarbamates# have been preparedby treating diamines with CS1[ Thus the reaction of m!phenylenediamine with carbon disul_de andammonium hydroxide gave the bis"dithiocarbamate# in 69) yield ð75MI 506!94Ł[ Dialkylaminesreact similarly ð76ZPK0718Ł[ The reaction of ethynyl ketones\ ArCOC2CTMS\ with amines andcarbon disul_de in MeCN gave the adducts ArCOCH1C"TMS#SC"1S#NR1 ð89ZOB591Ł[

(93)+ S • S +R12NH XR2 R1

2N S XR2

S

X = O, S

"iii# From isothiocyanates

Two general procedures for obtaining dithiocarbamates from isothiocyanates are outlined inEquation "83# and in Scheme 39[ The addition of thiols to isothiocyanates is represented by thereaction of benzenethiol and phenyl isothiocyanate to give 62) of S!benzyl N!phenyl dithio!carbamate ð70CCC0869\ 73CCC0466Ł and by the addition of methanethiol to penta~uorosulfanylisothiocyanate ð73CB0696Ł[ The general procedure of Scheme 39 is illustrated by the reaction ofbenzoyl chloride\ potassium isothiocyanate\ and alkanethiols ð70ZAAC"365#6\ 71JMC446Ł[ The additionof potassium isothiocyanate and benzenethiol or methanethiol to a solution of 2!chloro!benzoðbŁthiophene!1!carbonyl chloride similarly gives the dithiocarbamates ð73JPR522Ł[ In ananalogous reaction\ S!ethyl and S!propyl isothiocyanodithioformic acids are obtained fromRSC"1S#Cl "R�Et\ Pr# and potassium isothiocyanate in the presence of phase!transfer catalyst\07!crown!5 ð73ZAAC"401#120Ł[

(94)R1N • S + R2SHR1HN SR2

S

R1 Cl

O+ KNCS

R1 N

O

•S

R2SH R1HN

O

R2

S

Scheme 40

Carbonyl diisothiocyanate reacts with a range of nucleophiles to give cyclic dithiocarbamates"Scheme 30# ð70CB0021\ 70CB1964Ł[ Analogous reactions of carbonyl isocyanate isothiocyanate havebeen described ð70CB1953Ł[ N!"1\5!Dimethylphenyl#!N!isothiocyanatomethyl chloroacetamidereacts with aqueous sodium hydrogen sul_de giving\ after stirring for 0 h\ 1!"1\5!dimethylphenyl#!5!oxo!1!thioxo!hexahydro!0\2\4!thiadiazepine in 75) yield ð75S706Ł[

Several 0\2!thiazolidine!1!thiones were prepared from 0!iodo!1!isothiocyanatocycloalkane andsodium sul_des^ an example is shown in Equation "84# ð70JCS"P0#41Ł[ 0\2!Thiazine!1!thiones areformed by the cyclization of appropriate dithiocarbamates[ For instance\ treatment of PhCH!1CRC"1O#NCS "R�H\ Me\ Ph# with NaSH in methanol gave dithiocarbamatesH1NC"1S#SCHPhCHRCO1Me which then cyclized to 1!thioxo!0\2!thiazin!3!ones ð89MI 506!90Ł[


N N

O

•S

•S

HN

S

NH

O

S X

HN

S

N

O

S XR

HN

S

N

O

S NR2

H2O or H2S

ROH or RSH

R2NH

X = O, S

Scheme 41

Similarly\ the condensation of RCOCHR0CR1R2NCS with NaHS gave RCOCHR0CR1R2NHC"1S#S−Na¦ which reacted with iodomethane to a}ord the corresponding S!methyl dithio!carbamates[ With mineral acids the latter give the corresponding dithiocarbamic acids and theirring tautomers\ thiazinethiones ð80KGS305Ł[ 1!Thioxo!5!nitro!1\2!dihydro!3H!0\2!benzothiazin!3!one can be obtained by the reaction of 1!chloro!4!nitrobenzoyl isothiocyanate with sodium hydrogensul_de ð81MI 506!92Ł[

N•

S

INa2S

NH

SS (95)

"iv# From thiocarbamoyl chlorides

Several dithiocarbamates were prepared by stirring a mixture of a thiophenol\ dimethyl!thiocarbamoyl chloride\ potassium t!butoxide\ and DMF at room temperature\ as illustrated inEquation "85# ð80CPB0828Ł[ The reaction of benzimidazole!1!thiol with N\N!diethylthiocarbamoylchloride in the presence of anhydrous potassium carbonate in re~uxing THF a}orded the cor!responding dithiocarbamates ð74JHC0158Ł[ Reactions of thiazolidine!1!thione with thiocarbamoylor thiocarbazic acid chlorides led to S!substitution products "Scheme 31# ð81AP"214#062Ł[

(96)Me2N Cl

S+ PhSH

Me2N SPh

S+ KCl

KOBut

Scheme 42

HN S

SMe2N S S

NS

Me2N(Me)N S S

NSMe2N Cl

S

Me2N(Me)N Cl

S

"v# From thiuram disul_des

N\N!Dimethyl dithiocarbamates can be prepared from thiuram disul_des as shown in Equation"86# ð82S372Ł[ This approach has been used with other aryllithium derivatives ð76JHC638Ł[ Com!pounds of the type R0

1TeðSC"1S#NR11Ł1 were obtained by reaction of dimethyltellurium with


thiuram disul_des ð77ZAAC"445#068Ł[ Sodium cyclopentadienide cleaves thiuram disul_des] afteracidi_cation\ a mixture of tautomeric S!cyclopentadienyl dithiocarbamates was isolated ð82H"24#66Ł[

RLi

Me2N SR

S

Me2N S

S

S NMe2

S

(97)

"vi# Other methods

S!Methyl N\N!dimethyl dithiocarbamate was prepared from dimethylamine and MeSC"1S#Clð76CB876Ł[ Similarly\ condensation of the latter with methylphenylamine gave the N!methyl!N!phenyldithiocarbamate ð72JOC3649Ł[ A few thiazolidine!1!thiones were prepared from vic!iodoal!kanecarbamates\ potassium S!ethyl dithiocarbonate\ and aqueous sodium hydroxide ð74H"12#0070Ł[A method of preparing N!hydroxydithiocarbamates is illustrated in Equation "87# ð74TL4832Ł[7!Hydrazino!4!chloro!2\3!dihydro!1\5!dimethylbenzopyran reacts readily with allyl chloro!dithioformates in the presence of diisopropylethylamine "Hu�nig|s base# to give the correspondingallyl hydrazinecarbodithioates ð77JOC27Ł[

(98)PhS Cl

S+ MeNHOH

PhS NHOH

S


6.18Functions Containing aThiocarbonyl Group Bearing TwoHeteroatoms Other Than aHalogen or ChalcogenJOSE BARLUENGA, EDUARDO RUBIO and MIGUEL TOMASUniversidad de Oviedo, Spain

5[07[0 THIOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE NITROGENFUNCTION "AND NO HALOGEN OR CHALCOGEN FUNCTIONS# 458

5[07[0[0 Thiocarbonyl Derivatives with Two Nitroèn Functions 4585[07[0[0[0 From isothiocyanates 4585[07[0[0[1 From carbon disul_de 4635[07[0[0[2 From thiophosène 4655[07[0[0[3 From thiocarbonyl transfer reaènts 4665[07[0[0[4 From ureas 4675[07[0[0[5 Miscellaneous methods 479

5[07[0[1 Thiocarbonyl Derivatives with One Nitroèn and One Phosphorus Function 4795[07[0[1[0 From isothiocyanates 4705[07[0[1[1 From halothioamides 4735[07[0[1[2 From thiophosphinoyldithioformates 473

5[07[1 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION 473

5[07[0 THIOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE NITROGENFUNCTION "AND NO HALOGEN OR CHALCOGEN FUNCTIONS#

5[07[0[0 Thiocarbonyl Derivatives with Two Nitrogen Functions

The synthesis of thioureas and their derivatives have been reviewed previously ð68COC"2#262\72HOU"E3#396Ł[ This chapter has been organized according to the principal reagents used as primarysources for the synthesis of these compounds[

5[07[0[0[0 From isothiocyanates

Isothiocyanates are\ probably\ the most powerful starting materials for preparing thioureas andderivatives[ Thus\ in a general manner\ alkyl or aryl isothiocyanates react with ammonia\ primaryamines\ and secondary amines to give 0!substituted\ 0\2!disubstituted and trisubstituted thioureas\respectively ð44CRV070Ł[ This reaction generally takes place with good yields and works better inpolar solvents such as diethyl ether\ ethanol\ water\ or acetone "Equation "0##[ One of the main

458

469 Thiocarbonyl and Two Other Heteroatoms

advantages of the method is its versatility\ allowing the use of reagents with a wide range ofsubstitutents\ both in the amine and in the isothiocyanate components[

N •

R1

S+

S

R1HN NR2R3N

R2 R3

H(1)

R1 = alkyl, ArR2, R3 = H, alkyl, Ar

35–100%

The amine component can be extensively functionalized[ Thus\ v!aminoalcohols and amino!phenols react chemoselectively in boiling chloroform with isothiocyanates through the aminogroup exclusively "Equation "1## ð64JMC89Ł[ Aminothiols also react with phenyl isothiocyanatethrough the amino group\ while alkyl isothiocyanates produce a 0 ] 0 mixture of isomers "0# and "1#resulting from competitive addition of the amino and the thiol group[ If the hydrochloride derivativeis used instead of the free amine\ the reaction leads to the exclusive formation of the dithiocarbamatederivative "1# "Scheme 0# ð52JOC2039Ł[

N •

R1

S

S

R1HN NN

R2

H

OH+ (2)( )n

R2

( )

CHCl3

reflux OHn

N •

R1

S+

S

R1HN N

NR2

H

SH( )n

( )R1 = Ph

R1 = alkyl

R2

SHn

S

R1HN N( )

R2

SHn

S

R1HN S( )

NHR2n+

(1) (2)

47–66%

Scheme 1

Hydroxylamine and substituted hydroxylamines react with alkyl and aryl isothiocyanates to givethe corresponding hydroxythiourea derivatives "2# in variable yields^ the best results are obtainedwith aromatic isothiocyanates and N! or O!alkylhydroxylamines\ while isothiocyanates havingbulky substituents\ such as t!butyl\ give rise to lower yields "Equation "2#\ Table 0# ð0786JPR60\55PHA12\ 58ACS213Ł[

N •

R1

S

S

R1HN NN

R2 OR3

H

OR3+ (3)

R2

31–97%

Table 0 Thioureas "2# from hydroxylamines and isothio!cyanates[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR0 R1 R2 Yield Ref[

")#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐMe H Me 41 55PHA12Bun H H 37 55PHA12But H H 20 69JMC266Ph Me H 86 50AP654Ph H Et 59 58ACS213*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ


Steroids containing fused heterocycles\ such as the thiazole ring\ have been the subject of attentiondue to the in~uence exerted by the heterocyclic component on their pharmacological behavior[ Thistype of compound has been prepared stereospeci_cally by employing a general method of ringexpansion of N!thioacylaziridines[ Thus\ steroidal 1\2!aziridines react with phenyl isothiocyanateto give unstable thiourea intermediates which\ with sodium iodide\ undergo ring expansion to givethe _nal derivatives "3# and "4# "Scheme 1# ð79JCS"P0#655Ł[

OO

HN

N

S

PhHN S

NPhHN

OO

HN

PhNCSN

S

PhHN NaI

78%

S

NPhHN

NaI

66%

PhNCS

(4)

(5)

Scheme 2

The N0Si bond of trimethylsilylamines has also been found to insert into the C1N bond ofisothiocyanates[ The reaction takes place in ether at room temperature to give N!silylated thioureas\which can in turn be easily hydrolyzed to the corresponding derivatives "Scheme 2# ð68LA152Ł[

N •

R1

S

S

N NNR2 R2

TMSTMS

R1

R2

R2

S

N NHR1R2

R2

+R1 = Me, R2 = Et, 75%

Scheme 3

In a similar way\ trimethylstannylthioureas have been prepared in essentially quantitative yieldfrom phenyl isothiocyanate and stannylamines ð54JCS1046Ł[ This aminostannylation reaction ise}ected under mild conditions and appears to involve a cyclic transition state as suggested by thelow activation parameters found "Scheme 3#[

N •

Ph

S NMe Me

SnMe3+

S

N NMe2Ph

SnMe3

Scheme 4

N •

Ph

S

NMe3Sn

Me

Me

The N0H bond of imines also reacts with isothiocyanates[ For instance\ diphenylmethyleneaminereacts with phenyl isothiocyanate to give methylenethioureas "5#\ which have the structure of 1!amino!2!aza!0!thiabutadienes ð89JOC0610Ł[ The same compounds are obtained by reacting methyland phenyl isothiocyanate with N!tributylstannyldiphenylmethyleneamine ð61JCS"P0#029Ł[ TheN!phenyl derivative is stable and may also be prepared frombis"tributyltin# oxide and N!phenyl!N?!diphenylmethyleneaminothiourea in boiling benzene[ Methyl isothiocyanate\ however\ undergoesaddition at the carbonÐsulfur double bond and requires hydrolysis to yield the thiourea derivative[The related reaction of N!silylated methyleneamines is also known and represents a more generalentry into this type of compound ð61JCS"P0#0567\ 78S117Ł[ Another approach to these compoundsinvolves the reaction of secondary amines with 0!bromoalkyl isothiocyanates^ the reaction takesplace in ether at low temperature\ and the brominated intermediate is transformed with loss ofhydrogen bromide into the azathiabutadiene "Scheme 4# ð68CB0845Ł[

An interesting example of the insertion of a nitrogenÐmetalloid bond into isothiocyanates is the


N

Ph

PhS

NHR

N

Ph

PhHN •

R

S

N

Ph

PhS

S SnBu3

N

Ph

PhS

N R

Bu3Sn

N •

R

S N

Bu3Sn

Ph

Ph

N

R2

R3S

N R1

TMS

N •

R1

SN

TMS

R2

R3

R3 = H, Ar

N • S

59–92%+

H2O

+ N

R2

R2

+50%

H

(Bu3Sn)2O

+

–HBr

R1 = c-C6H11; NR22 = piperidino, 90%

R = Me, Ph

N

R1

S

N R2

R2

Scheme 5

(6)

R1

Br

reaction of diazaboracyclohexane with phenyl isothiocyanate which results in the formation of therare eight!membered boratriaza heterocycle "6# "Equation "3## ð65JOM"009#04Ł[

NN

BN

NB

NH

Ph

HSH

Ph

Ph

H

N • S

Ph+

CCl4

90%(4)

(7)

Functionalized isothiocyanates appear to be adequate starting materials for the synthesis ofN!unsubstituted thioureas for which the preparation seems to be otherwise di.cult or requirescumbersome procedures[ For instance\ alkanoyl isothiocyanates\ easily available from acid chloridesand lead"II# thiocyanate\ react with secondary amines in acetone to yield N!alkanoylthioureas whichare in turn deprotected with aqueous base ð44OSC"2#662\ 76JCS"P0#0042Ł[ Thioureas of this sort arealso available by reaction of alkoxycarbonyl isothiocyanates with amines followed by acid hydrolysisof the carbamate moiety "Scheme 5# ð62JPR033Ł[

Silicon"IV# isothiocyanate reacts in benzene with secondary amines to give\ after solvolysiswith a mixture of water and isopropanol\ 0\0!disubstituted thioureas ð62OSC"3#790Ł[ Phosphorusderivatives\ such as 1!isothiocyanatobenzo!0\2\1!dioxophosphole\ react with secondary amines tofurnish the corresponding addition compounds "7#^ further treatment with aqueous sodium hydrox!ide allows the removal of the phosphorus group yielding 0\0!disubstituted thioureas "Scheme 6#ð60LA"632#056Ł[

In what constitutes a special reaction\ aliphatic and aromatic isothiocyanates dimerize on heatingin DMSO to a}ord N\N?!symmetrically substituted thioureas "Equation "4## ð63S178Ł[

N • S S

NHR

NHR

R(5)

DMSO, heat

32–87%

R = Me, Tol, 4-Cl-C6H4


N

S

N R2

R2

N • S

+ N

R2

R2

H

H

COR1

30–99%O

R1

NH2

S

N R2

R2N

S

N R2

R2

N • S

+ N

R2

R2

H

H

CO2R1

42–63%O

OR1H3O+

OH–

Scheme 6

N • S N

R

R

HSiSi N

H

S

N

R

R

S

NH2

N

R

R

N • S N

R

R

HS

NH2

N+

R

R

NaOH

40%N

H

S

N

P R

R

O

O

Scheme 7

+

PO

O

PriOH, H2O

–SiO2

4

4

(8)

The synthesis of heterocyclic derivatives of thioureas has been reviewed by Mukerjee and Ashareð80CRV0Ł[ The strategies developed are based on the idea of the counter!attack reagent\ since thethiourea adduct resulting from the addition of one equivalent of amine to an isothiocyanate mightstill undergo a subsequent intramolecular cyclization if adequate functionalization is present[ Aminoacids and their derivatives\ amino aldehydes\ amino ketones\ amino oximes\ hydrazines\ and hydra!zides are among the many reagents employed for this purpose[ Thus\ a wide variety of _ve! and six!membered heterocycles has been easily prepared "Equation "5##[

N • S

RH2N

X

+N Y

N

R

SH

( )n

n = 1, 19–49%; n >1, 15–85%

Y = CH(OH)Y = CR(OH)Y = C=O

n = 1, 2

X = CHOX = RC=OX = CO2H, CO2R

( )n(6)

Thiosemicarbazides are also prepared in a general manner from isothiocyanates[ Thus\ alkyl andaryl isothiocyanates react exothermically with mono!\ di!\ or trisubstituted hydrazines\ as well aswith hydrazine itself\ to give thiosemicarbazides in good yield[ When unsymmetrical mono! anddisubstituted hydrazines are employed both of the two possible regioisomers "8# and "09# are actuallyobtained\ although the thiosemicarbazides resulting from the attack of the less!substituted nitrogenpredominate in the case of monosubstituted hydrazines "Scheme 7# ð50ZOB2615\ 69MI 507!90Ł[

Another entry into thiosemicarbazides is provided by the reaction of isothiocyanates\ preparedfrom azides and carbon disul_de\ with triphenylphosphine and hydrazine[ However\ the yieldsobtained through this method are only moderate "Scheme 8# ð81T6494Ł[

Functionalized hydrazines have also been used as suitable precursors of thiourea derivatives[ Forinstance\ acylhydrazines ð57JOC740\ 61TL1828\ 79JHC0258Ł and sulfonylhydrazines ð69JMC223Ł reactregioselectively through the free amino group with isothiocyanates in ethanol to give thiosemi!carbazides in good yields "Equation "6##[


N • S N

R3

R4

N

S

NHR1

N

R2

N

+

(9)

R1N

H

R2

R3

R4

S

NHR1

N

R2

NHR3

(10)

+

R2, R3, R4≠ Hor R2 = R3

56–100%

R2 ≠ R3, R4= H S

NHR1

N

R3

NHR2

Scheme 8

ArN N

NH2

H

S

H

ArN3 Ar

N•

S

i, Ph3P

ii, CS2

H2N–NH2•H2O

26%

Scheme 9

Ar = Ph

N • S

S

NHR

N

R(7)+ H2N N

H

XH

NHX

OMeR = Ph, X = O2S

X = COR2, SO2R2

EtOH

88%

Thiosemicarbazides are also available from amino isothiocyanates[ In this case\ reaction of2!aminopyridine with substituted amino isothiocyanates represents another route to 0\0\3!tri!substituted thiosemicarbazides "Equation "7## ð57ACS0787Ł[

N • S

S

N

NN HR

R

H

N

R

R

N

N

H2NEtOH

40%+

R = Pri

(8)

It is also possible to obtain cyclic derivatives of thiosemicarbazides from properly functionalizedisothiocyanates following the same pattern described above for thioureas[ Thus\ hydrazine reactswith 1!acetoxyvinyl isothiocyanate in re~uxing ether to give 3\4!dihydro!0\1\3!triazine!2"1H#!thione"00# "Equation "8## ð68JCR"S#139Ł[

N

NN

H

S

H+ H2N NH2

N • S

O

O

ether, reflux

57%

(11)

(9)

5[07[0[0[1 From carbon disul_de

Symmetrical thioureas are synthesized inexpensively by reacting primary amines with carbondisul_de in the presence of a catalyst\ such as sulfur\ hydrogen peroxide\ hydroxide ion\ iodine\ orpyridine[ The reaction appears to involve an ammonium dithiocarbamate intermediate which upon


loss of hydrogen sul_de and addition of a second equivalent of amine yields 0\2!disubstitutedthioureas[ This reaction pathway is supported by the formation of unsymmetrical thioureas whenthe reaction is carried out in the presence of ammonia or other amine "Scheme 09# ð44CRV070Ł[

S

NHR1

NHR1(R2)

R1NH2

or R2NH2~100%

•S N

R1S

NHR1

SH–SH2

•S S + R1NH2cat.

Scheme 10

Trisubstituted thioureas are synthesized from carbon disul_de\ aliphatic or aromatic primaryamines and hexaalkylphosphorus triamides\ which transfer one of their dialkylamino groups[ Thereaction takes place in pyridine giving the thioureas in almost quantitative yield "Equation "09##ð64S273Ł[

(10)

R2 = Ph, Bn, c-C6H11

S

NR12

NHR2

•S S + (R12N)3P + R2NH2

pyridine

~100%

Carbon disul_de condenses with three molar equivalents of dialkylcyanamides at 099>C and highpressure to give substituted thiocarbamoylimino!0\2\4!thiadiazines "01# in good yields[ The reactionis thought to proceed through a repeated ð1¦1Ł cycloadditionÐretroaddition cycle "Scheme 00#ð89JCS"P0#0107Ł[

S

NR2

N

•S S + S

NR2

NR2N N

• S

N

S

N

NR2

NR2

500 MPa

100 °C

2 R2N N

NR2 = NMe2, pyrrolidine, piperidine, 55–84%

Scheme 11

(12)

Hydroxylamines show anomalous behavior towards carbon disul_de in DMF since the formationof monohydroxythioureas "02# instead of the expected N\N?!dihydroxy derivatives has been reportedto occur "Equation "00## ð69LA"620#060Ł[

S

NHR

N

R

OH•S S + RNHOH

DMF

82%

(13)

(11)

R = c-C6H11

As expected\ a\v!diamines react with carbon disul_de in ethanol to give cyclic thioureasð52FCF443Ł[ The method allows the preparation of heterocycles of various ring sizes\ includingmedium ring\ macrocyclic\ and benzocondensed products as is exempli_ed in Scheme 01 by thereaction of 0\7!diaminooctane ð79TL202Ł and 1!aminobenzylamine ð58JOC2593\ 60ZC01Ł with carbondisul_de[ Substituted pyrimidine!1"0H#!thiones "03# are available in a regioselective fashion byre~uxing 3!amino!0!azabutadienes in carbon disul_de "Scheme 01# ð68CC564\ 71JCS"P0#1038Ł[

1!Thiohydantoins are immediate precursors of imidazothiazoles\ potential central nervous systemantitumor agents[ These thiohydantoins are generally prepared in good yields from a!amino acidsor a!amino esters and isothiocyanates[ Alternatively\ they can be obtained in one pot by reactionof dithiocarbamic esters\ generated in situ from a primary amine\ carbon disul_de and methyl iodide\and a!amino acids "Scheme 02# ð72S280Ł[

The Schi} bases derived from aromatic aldehydes and arylamines are precursors of imidazole!1!thione in a reaction sequence that comprises three steps^ thus\ the sodium cyanide promoteddimerization of the imines in DMF giving the benzil dianil is followed by reduction with sodium inether and cyclization with carbon disul_de[ This method is restricted to all!aryl substituted com!


S•+ SN N

S

R R

( )n–2R

N NR

H H

∆

80–95%

∆

(14)

( )n

EtOH/H2O

13–72%

n = 1, 2, 6

N

N

NH2

NH2

H

S

HS•+ S

N

N

R2

R3 R1

SR4NH

NHR1

R2

R3

R4

S•+ S

Scheme 12

S

NHR

SMe

EtOHN N

O

H

S

RS • SRNH2 + MeI +

DL-alanine/Et3N

76–97%

Scheme 13

pounds since only aromatic aldimines undergo cyanide!catalyzed dimerisation to form dianils"Scheme 03# ð79S0990Ł[

Scheme 14

N

N

Ar2

S

Ar2Ar1

Ar1

Ar1 N

Ar2

Ar1 N

Ar2

NAr2Ar1 NaCN

DMF

i, Na, ether

ii, CS2

65%Ar1 = Ar2 = Ph

Carbon disul_de also inserts into the N0Si bond of siladiazoles to give an unstable intermediate"04# which readily decomposes to the corresponding thiourea[ The reaction takes place at or belowroom temperature and sometimes requires the use of a high excess of carbon disul_de ð80JOM"308#8Ł[Other reactive amines such as bis"tributyltin#ethylene diamine have also been reported to a}ordcyclic thioureas "Scheme 04# ð69MI 507!91Ł[

5[07[0[0[2 From thiophosgene

Substituted thioureas can also be prepared by reaction of thiophosgene with primary and sec!ondary amines[ This method is closely related to the one described in Section 5[07[0[0[0\ and involvesthe formation of isothiocyanates and thiocarbamoyl chlorides as the intermediates in the reactionwith primary or secondary amines\ respectively ð44CRV070\ 62RCR476Ł[ Accordingly\ when the reac!tion is carried out using equimolecular amounts of thiophosgene and secondary amine\ the cor!responding thiocarbamoyl chloride is isolated^ this intermediate can in turn react with anotherequivalent of a di}erent amine\ thus allowing the synthesis of unsymmetrically substituted thioureas"Scheme 05#[


N

N

NS

Si

N

R2

S

R3

S

R2R1

R1

R3

SiS

R1

R1N

Si

N

R2

R3

R1

R1

Bu3SnN N

SnBu3

H H+ S • S

N

N

H

S

H

83–87%

(15)

CS2 (1–10 equiv.)

25 °C

–

Scheme 15

S

NR1R2

NR1R2

HNR1R2

S

NR1R2

NR3R4

HNR3R4

S

NR1R2

Cl

HNR1R2

S

Cl

Cl

Scheme 16

77–87%

Thiophosgene also reacts with nitrogen heterocycles to give bis"heterocyclic# thiocarbonyl com!pounds which have found utility as thiocarbonyl transfer reagents in other syntheses of thioureaderivatives "see Section 5[07[0[0[3#[ The synthesis of these compounds can be achieved either fromN0H containing heterocycles\ mostly azoles\ or activated derivatives thereof[ For instance\ N!trimethylsilylimidazole reacts with thiophosgene in carbon tetrachloride at room temperature tofurnish N\N?!thiocarbonylbis"imidazole# "Equation "01## ð67JOC226\ 68LA0645Ł[

S

Cl

Cl

S

Het

Het

(12)

Het = NN

,

N

N, N

N,

NN

N

N

N

N

R = H, TMS

, ,

+ Het–R

As in the case of carbon disul_de\ aliphatic diamines produce cyclic thioureas ð64JCS"P0#101\64JMC802\ 79JMC0150Ł[ 0\2!Dimethyl!1\1!diethyl!0\2!diaza!1!germacyclopentane reacts with thio!phosgene at room temperature to give 0\2!dimethylimidazolidine!1!thione "05# in 67) yield "Equa!tion "02## ð64JOM"77#C24\ 80JOM"308#8Ł[

(13)S

Cl

Cl

+ N

N

Me

Me

SN

Et2GeN

Me

Me

78%

(16)

5[07[0[0[3 From thiocarbonyl transfer reagents

As has been indicated above\ heterocyclic thiocarbonyl transfer reagents have been used increas!ingly for the synthesis of thiourea derivatives[ For instance\ N\N?!thiocarbonyl!bis"imidazole# reacts


with two equivalents of aliphatic or aromatic primary amines in CH1Cl1 or chloroform at roomtemperature to give 0\2!disubstituted thioureas in nearly quantitative yield ð67JOC226\ 79JCS"P0#655Ł[Secondary amines such as diethylamine expel just one imidazole group to furnish the mixed thiourea"06# "Scheme 06# ð51LA"546#87Ł[ The other azoles studied\ while usually less reactive\ may in certainsituations o}er some advantages due to their higher stability to moisture and the low solubility ofthe free heterocycle recovered "Scheme 06# ð67JOC226Ł[

S

NHR

NHR

S

N N

N N

S

NR2

N

N

RNH2

90–100%

(17)

R2NH

Scheme 17

N\N?!Thiocarbonylbis"2\4!dimethyl#pyrazole has been reported to give N\N?!diphenylthioureaand benzimidazoline!1!thione on reaction with aniline and 0\1!diaminobenzene\ respectively[ When0\3!diaminobenzene is used the reaction results in the formation of a thiourea derived polymer[Aliphatic primary diamines show di}ering behavior depending on the length of the methylene chain[Thus\ while 0\2!diaminopropane and 0\3!diaminobutane form the bis"2\4!dimethyl!0!pyra!zolylthioformyl#diamines "DMP�2\4!dimethylpyrazolyl#\ 0\4!diaminopentane produces a thermo!plastic polymer "Scheme 07# ð50LA"535#85Ł[

S

NHPh

NHPh

S

N N

N N

PhNH2

70%

N

N

H

S

H

polymer

DMP N N DMP

S

HH

S

( )n

polymer

H2N NH2

NH2

NH2

H2N NH2( )n

H2N NH2( )5

Scheme 18

70%

n = 3, 70%n = 4, 80%

A particularly useful preparation of thiourea derivatives takes advantage of the in situ formationof thiocarbonylbis"imidazole# from imidazole\ carbon disul_de and a 1!halothiazolium salt "molarratio 1 ] 1 ] 0#\ thus avoiding the use of thiophosgene[ The utility of this in situ generated thiocarbonyl!bis"imidazole# has been demonstrated in the preparation of unsymmetrical thioureas "07# andthiosemicarbazides "08# by stepwise addition of two di}erent amines or an amine and hydrazinehydrate\ respectively "Table 1\ Scheme 08# ð77JOC1152Ł[

5[07[0[0[4 From ureas

The direct conversion of the carbonyl moiety into a thiocarbonyl function is possible in generalwith some phosphorus derivatives\ such as P3S09 and the popular Lawesson|s reagent[ Some examples


Table 1 Thioureas "07# and thiosemicarbazides "08#from thiocarbonylbis"imidazole#[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR0R1NH R2R3NH Yield

")#*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐPhCH1MeNH NH2 47PhMeNH NH2 64Morpholine NH2 37PhCH1MeNH NH1NH1 = xH1O 30PhMeNH NH1NH1 = xH1O 63Morpholine NH1NH1 = xH1O 41PhMeNH Piperidine 77*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

NHN NN

S

SNa

S

N S N

S

NN

NS

Ph

XR

N N

S

NN

S

NR1R2

NR3R4

Y–+

(0.5 equiv.)

(18)

S

NR1R2

NHNH2

NaH, CS2

THF, 0 °C X = Br, ClY = BF4

–, FSO3

–CS2

(19)

i, R1R2NHii, R3R4NH

i, R1R2NHii, NH2NH2

48–88%

41–74%

Scheme 19

involving P3S09 and tetrasubstituted thioureas have been described[ The yields vary from moderateto poor ð60LA"635#81Ł\ a notable exception being the transformation of imidazolidin!1!one into thethione "19# which has been achieved in nearly quantitative yield "Equation "03##[

N NR R

O

P4S10

~100%N NR R

S

(20)

(14)

High yields are obtained with some heterocyclic derivatives[ Thus\ 0\3\5!trisubstituted 1"0H#!pyrimidones are converted into the corresponding pyrimidine!1!thiones "10# by re~uxing in benzenewith Lawesson|s reagent[ In this case the yields vary from poor to quantitative "Equation "04##ð71H"08#1172Ł[

(15)

N

N

O

R2

R3

R1Lawesson's reagent

benzene, reflux15–100% N

N

S

R2

R3

R1

(21)R1 = H, Me, ArR2 = Me, ArR3 = Me, Ar


5[07[0[0[5 Miscellaneous methods

A nearly quantitative conversion of symmetrical thioureas into unsymmetrical thioureas\ byexchange of one amino group\ has been described ð82TL5336Ł[ The process is accomplished byre~uxing 0\2!diphenylthiourea with di}erent types of amines and triethylamine in acetonitrile givinghigh yields of 0!phenylthiourea derivatives "11#^ the reaction also works\ though in lower yields\ inother polar solvents such as methanol\ ethanol\ THF\ or DMF[ The procedure has also been shownto take place under phase transfer catalysis\ thus allowing aqueous solutions of low boiling pointamines to be used "Equation "05##[ Sodium cyanothioformate reacts with primary diamines inre~uxing butanol to a}ord heterocyclic derivatives "12# in good yields "Equation "06## ð44MI 507!90\70JPR30Ł[

S

NHPh

NHPh

+ R1R2NHEt3N, MeCN

reflux70–90%

S

NHPh

NR1R2

(22)

(16)

(17)S

CN

SNa+ H2N(CH2)nNH2

BunOH

reflux81–89%

S

(23)

N

N( )n

H

H

n = 1, 2

Thiourea S\S!dioxide derivatives have found application in the reduction of di}erent compounds\such as dinitrodiaryl derivatives ð77AJC884Ł\ organoselenium and tellurium halides\ and oxidesð77SC290Ł as well as azobenzenes ð77MI 507!90Ł[ Thiourea itself can be quantitatively converted intoits dioxide by treatment with H1O1 and sodium acetate in water at 4>C ð89MI 507!90Ł[ The S\S!dioxides derived from monosubstituted thioureas are stable and can be obtained in a similar wayby treatment with two equivalents of hydrogen peroxide in ethanol at low temperature ð58LA"611#79Ł[When the thiourea bears bulky substituents at both nitrogen atoms\ the oxidation process stops atthe S!oxide stage ð58LA"611#41Ł[ The oxidation of the thioxo function of 0!aryl thiosemicarbazideswith hydrogen peroxide leads to the S!oxide derivative but it is also accompanied with the additionaloxidation of the hydrazo group to the azo function "Scheme 19# ð55TL2584Ł[

S

NH2

NH2

O2S

NH2

NH2

S

NH2

NHR

O2S

NH2

NHR

S

NHBut

N

OS

NHBut

N

H Et H Et

Scheme 20

S

NH2

N

H2O2 OS

NH2

N

H

NHAr

H2O2, NaOAc, H2O

97%

NAr

H2O2, EtOH

48%

30% H2O2, EtOH

64%

R = Prn

5[07[0[1 Thiocarbonyl Derivatives with One Nitrogen and One Phosphorus Function

Phosphinothioformamides\ also named thiocarbamoylphosphines\ are generally used as ligandsin organometallic chemistry[ The related compounds containing nitrogen and one atom of group04 other than phosphorus "As\ Sb\ Bi# are not known[


5[07[0[1[0 From isothiocyanates

Isothiocyanates are the most valuable source for preparing phosphinothioformamides[ Typically\the P0H bond of phosphines adds to isothiocyanates to give the title compounds "Equation "07##ð76ZN"B#66Ł[ Thioalkyl phosphines\ prepared from sodium phosphines and chloroalkyl thiols\ reactwith PhNCS to give the thioalkylphosphinothioformamide derivatives which can undergo a sub!sequent intramolecular cyclization to the thiocarbonylphosphazine "13# "Scheme 10# ð62JPR360Ł[Bis"ethylthio#alkylphosphines undergo reduction of the phosphorusÐsulfur bond with dibutyltindihydride giving rise to the corresponding species with a P0H bond\ which yields alkylthiophos!phinothioformamides upon reaction with phenyl isothiocyanate "Scheme 11# ð77ZOB0357Ł[ Thereaction of phosphonate and thiophosphonate isothiocyanates with secondary phosphines resultsin the formation of the corresponding phosphonates and thiophosphonates "Equation "08##ð81PS"62#70Ł[

N • SS

NHR2

P

R2

H +P

Ph

R1R1

Ph(18)

N • SS

NHPh

P

PhH +P

Ph

PhHS

SH

N

PPh

Ph

S–H2S

(24)Scheme 21

S

NHPh

PR1P

H

R1

SEtEtS

PhNCS

49–67%R1 + Bu2SnH2P

EtS

EtS

Scheme 22R1 = But, Et, SEt

(19)N • S

S

PR12

N(PriO)2(X)P

H P

R1

R1H

P(X)(OPri)2+

X = O, S

The P0H bond of phosphorus"V# derivatives also adds to isothiocyanates to yield phos!phinothioformamides "Equation "19## ð58BCJ1864\ 76ZN"B#759Ł[ Chiral phosphinothioformamides"14# are obtained when using isothiocyanates prepared from optically active amines\ such as "S#!and "R#!phenylethylamine "Equation "10## ð75ZN"B#0031Ł[ "N!Alkylthiocarbamoyl#phosphonic acidesters "15# have been prepared and shown to be versatile precursors of a!substituted methyl phos!phonate derivatives which display interesting biological activity[ Their preparation cannot beachieved by the Arbuzov!type reaction of trialkyl phosphites and isothiocyanates[ However\ whendialkyl phosphates are used instead\ the reaction works well and addition of the P0H bond to theC1N double bond of the isothiocyanate takes place[ The process is base catalyzed and the reactionis usually run in the presence of alkoxide ion\ except for compounds sensitive to these reagents suchas phosphonates^ in these cases\ triethylamine is a good alternative "Equation "11## ð64ZOB0373\71JOC2901Ł[ The related "N!alkylthiocarbamoyl#thiophosphonic acid esters have been prepared in asimilar way by starting from the corresponding thiophosphonic esters "Equation "12## ð72JOC2855Ł[

N • S

S

P(O)Ph2

N

H

R

R

RR

P

O

Ph H Ph

(20)+


N • S

S

P(O)Ph2

N

H Ph

Ph P

O

*

(25)

Ph H Ph

*(21)+

N • S

S

P(O)(OR2)2

N

R1

H

R1+ P

O

(26)

R2O H R2O

R1 = Me, BnR2O = OMe, OPh(R2O)2 = O(CH2)3O

(22)base

25–85%

N • S

S

P(S)(OR2)2

N

R1

H

R1+ P

S

R2O H R2O

(23)30–70%

Trimethylsilyl tetraethylphosphorodiamidite reacts with phenyl isothiocyanate yielding\ afterhydrolysis of the N0Si bond\ the thiocarbamoylphosphonate derivative "16# "Scheme 12#ð65IZV344Ł[ Thiocarbamoylphosphonic acids have also been prepared by reaction of tris"trimethyl!silyl# phosphite with alkyl and aryl isothiocyanates[ The exothermic reaction takes place very rapidlyat room temperature to give an adduct which upon treatment with aniline in methanol furnishesthe monoanilinium salt of thiocarbamoylphosphonic acid "17# in almost quantitative yield "Scheme13# ð68TL2902Ł[

N • S

S

P(O)(NEt2)2

NPh

Ph

H+ (Et2N)2P–OTMSH3O+

87%

(27)

S

P(O)(NEt2)2

N

Ph

TMS

Scheme 23

N • SS

P

N

R

R

H

Scheme 24

RN

P

S TMS

OOHO– +NH3Ph

OO-TMSO-TMS

(28)

PhNH2, MeOH

90–98%+ P(O-TMS)3

Alkyl and aryl isothiocyanates react with trimethylsilyldiphenylphosphine at 79>C to give theexpected N!silylated derivatives arising from addition of the P0Si bond\ which undergo easymethanolysis producing diphenylphosphinothioformamides "18# "Scheme 14# ð57JCS"A#0094Ł[ Theinsertion of isothiocyanates into the P0Si bond has also been described in several other phosphorusderivatives^ thus\ bis"trimethylsilyl#phosphines give similar insertion products with phenyl iso!thiocyanate "Equation "13## ð74ZAAC"419#019\ 74ZAAC"419#028Ł[ The P0Si bond of trimethylsilylphosphatriafulvenes also inserts into the C1N bond of isothiocyanates yielding compounds "29#through the betaine intermediate shown "Scheme 15# ð80S0988Ł[ Silylphosphines and germylphos!phines react at room temperature\ in almost quantitative yield\ with equimolar amounts of phenylisothiocyanate to give the corresponding phosphinothioformamide derivatives "20#[ The reactionproceeds with retention of the con_guration at the silicon or germanium centers suggesting a four!center mechanism "Equation "14## ð68TL2496Ł[


R = alkyl, aryl

N • S

S

PPh2

N

R

R

H+ Ph2P-TMS

MeOH

67–70%

S

PPh2

N

R

TMS

(29)

Scheme 25

(24)N • S

S

P

N

Ph

Ph

TMS+ RP(TMS)2

R

TMS

R = Me, Ph, But, mesityl

S

N

P

TMS

R

P-TMS

But

But

N •

R

S

But

But

P+ +

TMS

N

S

(30)

But

But –

65–73 %

R

Scheme 26

N •

Ph

SM

S

PEt2

N

Ph

M

MeEt2P Me

+ (25)

(31)M = Si, Ge

Phosphorus"III# acid amides react rapidly with isothiocyanates to form an addition intermediatewhich\ upon hydrolysis\ furnishes phosphinothioformamides "21# "Equation "15## ð66IZV0066Ł[ Also\phosphorus"V# acid t!butyl esters and amides react with phenyl isothiocyanate to give phos!phinothioformamides "Equation "16## ð89ZOB452Ł[

(26)S

P(OR)NHPh

N

O

Ph

H

(32)

i, PhNCS

ii, H2O(RO)2PNHPh

S

PR2

N

O

Ph

H62–82%

+ N •

Ph

SP

O

R But

R

(27)

R = EtO, Me2N

N!Thiophosphonate phosphinothioformamides "22# can be prepared by reaction ofdialkoxythiophosphoryl isothiocyanates with sodium dialkylphosphites in ethanol[ However\ theyield in this reaction is very low\ and heating in benzene does not improve the synthesis of "22#\ butresults in phosphonateÐthiophosphate rearrangement "Equation "17## ð82ZOB522Ł[

(33)

S

P(OEt)2

N

O

H

P(S)(OPri)218%

+ (EtO)2PONa

N •

(PriO)2P

S

S

(28)


5[07[0[1[1 From halothioamides

Chlorothioamides are the main alternative to isothiocyanates for preparing thiocarbonyl deriva!tives containing nitrogen and phosphorus atoms[ Thus\ lithium diphenylphosphide reacts withN!alkyl! and N!arylthioformamidoyl chlorides to give diphenylphosphinothioformamides "23# in43Ð62) yield ð74CB116Ł[ Good yields are also obtained in the reaction of lithium trimethyl!silylphosphides with thioformamidoyl chlorides to give the trimethylsilylphosphinothioformamidederivatives "24# ð73ZAAC"407#10Ł[ Phosphorus"III# esters react with dialkylamides of chloro!thioformic acid to give phosphinothioformamides "25# in moderate to good yields "Scheme 16#ð77ZOB0378Ł[

P Ph

R1N

S

R1

Ph

(34)

R1 = Me, Ph57–73%

P TMS

R1N

S

R1

R2

(35)

R1 = MeR2 = Me, But, Ph, TMS

P OR3

R1N

S

R1

R2

(36)

R2 = Me, EtR3 = Et, Pr, Bu

Ph2PLi

R2P(TMS)Li

77–89%

R2P(OR3)2

45–83%

Cl

R1N

S

R1

Scheme 27

5[07[0[1[2 From thiophosphinoyldithioformates

Substituted thiophosphinoylthioformamides "26# are obtained by aminolysis reaction of thiophos!phinoyldithioformates[ The reaction works well for ammonia and primary aliphatic amines withmoderate steric hindrance "Equation "18## ð69ACS0983Ł[

(29)S

SR3

PR1R2

S

S

NHR4

PR1R2

S

(37)

R4NH2

R4 = H, alkyl

5[07[1 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION

Thiocarbonyl compounds bearing metalloid functions are almost unknown[ Two di}erentapproaches for the synthesis of bis"trimethylsilyl#thioketone have been described up to now\ andsome controversy has been generated concerning the stability of this compound[ Block et al[proposed in 0874 the intermediacy of bis"trimethylsilyl# thioketone "27# in the serendipitous synthesisof alkyltrimethylsilyldithioformates from alkanesulfenic acids[ This bis"trimethylsilyl# thioketonewas prepared by pyrolysis of the corresponding thiosul_nate and trapped in situ with 1\2!dimethyl!


butadiene to give the corresponding DielsÐAlder cycloadduct[ In the absence of the trapping agent\the major product is the trimethylsilyldithioformate "28# "Scheme 17# ð74TL1148\ 77T170Ł[

SH +TMS

TMS

OS

Cl

Et

S

TMS

TMS

S

Et

O

S + EtSOH

TMS

TMS

S

TMS

TMS

S

EtS

TMS

heat

46%

pyridine

–TMS-OH

2,3-dimethylbutadiene

Scheme 28

(38)

22%

(39)

Ricci et al[ almost simultaneously reported the _rst synthesis of bis"trimethylsilyl# thioketone "27#starting from tris"trimethylsilyl#methane[ Thus\ the treatment of the latter with one equivalent ofMeLi followed by addition of elemental sulfur and acidic hydrolysis leads to tris"trimethyl!silyl#methanethiol which is transformed into tris"trimethylsilyl#methanesulfenyl bromide by reactionwith MeLi and bromine[ Finally\ heating of the sulfenyl bromide results in loss of bromo!trimethylsilane and formation of the target compound "27# "Scheme 18# ð74TL0980Ł[

TMS

TMS

TMS heat

–Br-TMS50%

S

TMS

TMS

(38)

SH

TMS

TMS

TMS SBr

TMS

TMS

TMS

i, MeLi ii, S8

iii, H3O+

i, MeLiii, Br2

Scheme 29


6.19Functions Containing aSelenocarbonyl orTellurocarbonyl Group—SeC(X)X? and TeC(X)X ?FRANK S. GUZIEC, Jr. and LYNN JAMES GUZIECNew Mexico State University, Las Cruces, NM, USA

5[08[0 OVERVIEW 476

5[08[1 SELENO! AND TELLUROCARBONYL FUNCTIONS CONTAINING AT LEAST ONEATTACHED HALOGEN 477

5[08[2 SELENOCARBONYL FUNCTIONS CONTAINING AT LEAST ONE ATTACHEDCHALCOGEN "AND NO HALOGENS# 477

5[08[2[0 Dialkoxy!substituted Selenocarbonates\ "RO#1C1Se 4775[08[2[1 Dithio!substituted Selenocarbonates "RS#1C1Se 4785[08[2[2 Selenocarbonyl Functions Flanked by Two Selenium Atoms\ "RSe#1C1Se 4895[08[2[3 Selenocarbonyl Functions Flanked by Two Different Chalco`en Atoms\ RX"C1Se#YR 4815[08[2[4 Selenocarbamates RO"C1Se#NHR\ RS"C1Se#NHR\ and RSe"C1Se#NHR 4825[08[2[5 Phosphorus!substituted Selenocarbonyl Derivatives 485

5[08[3 FUNCTIONS CONTAINING AT LEAST ONE NITROGEN FUNCTION "AND NO HALOGENOR CHALCOGEN FUNCTIONS# 485

5[08[3[0 Selenoureas "R1N#1C1Se 4855[08[3[1 Telluroureas "R1N#1C1Te 488

5[08[0 OVERVIEW

Initially it should be noted that examples of selenocarbonyl analogues of well!known carbonyl!based functional groups are much less common than the corresponding oxygen and sulfurcompounds[ The related tellurocarbonyl compounds are even more rare[ This scarcity is probablydue to a number of factors[ Selenocarbonyl and tellurocarbonyl compounds are much less stablethan their oxygen and sulfur analogues\ presumably owing to poor overlap in the p bonds of theselenium and tellurium compounds[ These compounds are also prone to lose volatile selenium andtellurium species and are therefore often unpleasant to work with and potentially toxic[ The earlyliterature associated with selenocarbonyl or tellurocarbonyl compounds is fraught with errors[ Eventhe nomenclature describing these analogues is often inconsistent\ leading to di.culties in searchingthe literature "e[g[\ the term {selenone| is often used incorrectly to designate a carbonÐseleniumdouble bond instead of the accepted term {selone|#[ A number of reports dealing with these problemshave been published ðB!62MI 508!90\ B!62MI 508!91\ B!75MI 508!90\ B!76MI 508!90\ B!76MI 508!91Ł[ On a

476

477 Selenocarbonyl or Tellurocarbonyl

positive note it should also be stated that advances in the availability of novel reagents for theintroduction of selenium and tellurium into organic molecules and progress in spectroscopic charac!terization may make further examples of these compounds more common in the near future[

5[08[1 SELENO! AND TELLUROCARBONYL FUNCTIONS CONTAINING AT LEASTONE ATTACHED HALOGEN

Compounds containing a halogen directly attached to a selenocarbonyl or tellurocarbonyl moietyare quite rare[ In addition\ very little has been reported on the reactions of these compounds[Selenocarbonyl di~uoride "0# is quite unstable to dimerization in solution and to polymerization inthe presence of Lewis acids[ It can be obtained by pyrolysis of the dimer at 259>C "Equation "0##\or on a preparative scale by treatment of aluminum triiodide with Hg"SeCF2#1 "Equation "1##ð79ZN"B#415Ł[ Its tellurium analogue "1# can be prepared similarly using diethylaluminum iodide asa Lewis acid "Equation "2## ð80CC0267Ł[ This compound is also highly reactive and prone todimerization[

(1)Se

Se

F

FF

F2 Se

F

F

360 °C

hν

(1)

(2)2 Se

F

FHg(SeCF3)2 + AlI3

(3)2 Te

F

FHg(TeCF3)2 + Et2AlI

(2)

Selenophosgene "2# can be prepared by vacuum pyrolysis of 1\1\3\3!tetrachloro!0\2!diseletane"Equation "3##\ but is stable only below −029>C ð70ZN"B#0150Ł[

(4)Se

Se

Cl

ClCl

Cl2 Se

Cl

Cl

>300 °C

(3)

A single example of a monosubstituted selenoacyl halide has been reported[ It is prepared startingfrom selenocarbonyl di~uoride "Equation "4## ð79ZN"B#415Ł[

(5)Se

F

F

Se

F

SeCF3

+ B(SeCF3)3

5[08[2 SELENOCARBONYL FUNCTIONS CONTAINING AT LEAST ONE ATTACHEDCHALCOGEN "AND NO HALOGENS#

Note that no tellurocarbonyl compounds of this class have been reported to date[

5[08[2[0 Dialkoxy!substituted Selenocarbonates\ "RO#1C1Se

Oxygen!substituted selenocarbonates are not particularly well represented in the literature\ andgenerally appear only as minor by!products in the preparations of selenium!containing compounds


ð77AJC438Ł[ Treatment of sugar!derived cis!vicinal diols with phosgeneiminium chloride "3#\ fol!lowed by sodium hydrogen selenide treatment\ a}orded the corresponding cyclic selenocarbonates"4# in good yield "Equation "5## ð77AJC438Ł[ This reaction is reported to fail in the case of catechol\a}ording instead the open!chain selenourethane "5# "Equation "6## ð77AJC438Ł[

(6)

HO

R R

OHO O

Se

R R

Me2N

Cl

Cl

CH2Cl2

(5)

+Cl–

NaHSe

(4)

+

(7)

OH

OH

Me2N

Cl

Cl

OH

O NMe2

Se

(4)

CH2Cl2 NaHSe+

(6)

+Cl–

5[08[2[1 Dithio!substituted Selenocarbonates "RS#1C1Se

Cyclic dithio!substituted selenocarbonates are important intermediates in the preparation oftetrathiafulvalenes[ A general route to these compounds involves alkylation of dithiocarbamateanions "6#\ readily obtained by reaction of secondary amines with carbon disul_de in the presenceof base\ followed by cyclization in strong acid to the corresponding iminium salts "7#[ Treatment ofthis isolable salt with NaHSe or H1Se a}ords the desired cyclic selenocarbonate "8# "Scheme 0#ð78JCS"P0#0957Ł[

N HN

S

S– K+

OMe

OMeBr

+ CS2KOH

(7)

S

SSe

S

SN+

N SOMe

OMe

NaHSe i, H2SO4, 60 °C

ii, NaBPh4

(9)(8)

SPh4B–

Scheme 1

The previously mentioned phosgeneiminium chloride route to dialkoxy!substituted seleno!carbonates can also be used in the preparation of dithio!substituted derivatives[ Treatment ofbutanethiol with Viehe|s salt "3#\ followed by addition of sodium hydrogen selenide\ a}orded thedithioselenocarbonate "09# in good yield "Scheme 1#[ Cyclic dithioselenocarbonate derivatives "00#and "01# have also been prepared using this method ð77AJC438Ł[

Me2N

Cl

Cl

Me2N

SBu

SBu

Se

SBu

SBu

+BuSH

(4) (10)

73%Cl–

NaHSe+ +

Cl–

Scheme 2

S

SSe

(11) (12)S

S

Se


Complex selenocarbonates can be prepared by direct metallation of 3\4!unsubstituted seleno!carbonates[ For example\ consecutive treatment of the cyclic unsaturated dithioselenocarbonate "8#with lithium diisopropylamide "LDA#\ selenium\ zinc chloride\ and tetrabutylammonium bromidea}ords a diselenolate salt that can be acylated to the complex selenocarbonate "02# "Scheme 2#ð81JOM"316#102Ł[

Similar metallation reactions have been reported for other selenocarbonate derivatives[

SeS

SSe

S

S

PhCOSe

PhCOSe

SeS

S

SeZn

Se

Scheme 3

2

(Bu4N)2

(13)(9)

i, LDA, THF, –78 °C ii, Se

iii, ZnCl2iv, Bu4NBr

PhCOCl

5[08[2[2 Selenocarbonyl Functions Flanked by Two Selenium Atoms\ "RSe#1C1Se

Compounds of this type are generally referred to as triselenocarbonates in the literature[ A varietyof preparations of this class of compounds\ particularly the cyclic triselenocarbonates\ have beenreported owing to their importance as intermediates in the preparation of tetraselenafulvalenes[ Theparent acid\ triselenocarbonic acid "03#\ can be prepared by acidi_cation of barium tri!selenocarbonate "Equation "7##[ It is unstable even at low temperatures\ liberating hydrogen selenideand polymeric selenium!containing materials[ The chemistry of this and related selenium!substitutedcarbonic acids has been reviewed ð57AG"E#757\ B!62MI 508!92Ł[

Se

SeH

SeH

H+

(14)

(8)BaCSe3

A number of triselenocarbonate preparations begin with carbon diselenide as a starting material["It should be noted that carbon diselenide is a remarkably unpleasant reagent and should be usedonly with great care ðB!62MI 508!93Ł[# Reaction of sodium acetylide with carbon diselenide in thepresence of selenium\ followed by acidi_cation\ a}ords the cyclic unsaturated triselenocarbonate"04# "Scheme 3# ð66JA4898Ł[ Electrochemical reduction of carbon diselenide\ followed by alkylationof the intermediate dianion\ can be used to prepare complex selenium!substituted tri!selenocarbonates such as "05# "Scheme 4# ð65CC037\ 72CC124Ł[ Heating 0\1\2!benzoselenadiazole inre~uxing xylene in the presence of a two!fold excess of carbon diselenide a}ords benzo!0\2!diselena!1!selone "06# in 58) yield "Equation "8## ð72CC184Ł[

SeSe

SeNaC CH

Se

Se Se– Na++ CSe2 +

Scheme 4

H+

(15)

Se

SeSe

SeSe

Se

Se

Se

Se

–Se

–Se

BrBr

(16)

CSe2e–

Scheme 5

(9)SeSe

SeN

N

Se

(17)

CSe2

∆


Treatment of alkyl halides with carbon diselenide and potassium hydroxide in dimethyl sulfoxidea}ords a variety of both cyclic and acyclic triselenocarbonates "07# in moderate yields "Equation"09## ð56ACS0870Ł[ It should be noted that the expected direct preparation of acyclic triseleno!carbonates via reaction of a selenolate with carbon diselenide\ followed by alkylation\ fails to a}ordthe desired product "Equation "00## ðB!62MI 508!94Ł[

(10)Se

RSe SeRRX + CSe2 + KOH

DMSO

(18)

R = –(CH2)2–, –(CH2)3–, –CH2Ph, –CH2CO2H, –Me

(11)Se

RSe Se–

Se

RSe SeR+ CSe2RSe–

Reaction of cyclic iminium intermediates such as "08# with hydrogen selenide provides a con!venient route to substituted unsaturated triselenocarbonates "Scheme 5 ð64JOC635Ł\ Scheme 6ð73CC78Ł\ Scheme 7 ð66CC494Ł and Scheme 8 ð79CC755A\ 79CC755BŁ#[ The required iminium salts canbe obtained by cyclization of diselenocarbamates[ The latter two approaches have the advantagethat they avoid the use of carbon diselenide as a source of selenium[

N

Se

NSe

Se

R

O

R

Se– BrR

O

R H2SO4HClO4+

NSe

SeSe

Se

Se

R

R

R

R

H2SeClO4

–+

Scheme 6

(19)

N Se

Se

N Se

Se

O

O

Se

2

+

2

NSe

SeSe

Se

Se

H+

H2SO4, 0°C H2Se

(15)

Scheme 7

+

O

RBr

R R O

R Se NMe2

NMe2Se

Me2N NMe2

+

+H2Se

NSe

SeR

R

SeSe

SeR

RMe

Me

R O

R Se NMe2

Se H2SeH+ +

Scheme 8


Se

Me2N Se– Et3NH

R

SeMe2N

Se

R

O

Me2N

Cl

Cl

+

+

H2Se

Et3N

RR

O

BrCl–

+

NSe

SeR

R

SeSe

SeR

RMe

Me

Scheme 9

H2Se

CF3CO2H

H2SO4

Thiocarbonyl compounds can similarly be converted to the corresponding selenocarbonyl deriva!tives by alkylation followed by hydrogen selenide treatment "Scheme 09# ð72CC183Ł[ The tri!selenocarbonate moiety has been incorporated into more complex structures by an extrusionÐcycloaddition sequence "Equation "01## ð78CC0419Ł[ The previously described metallation route toother selenocarbonates "Scheme 2# has also been used for functionalization of cyclic 3\4!unsaturatedtriselenocarbonates ð81JOM"316#102Ł[

SeSe

SeS

Se

SeS

Se

Se

Me(MeO)2

+ CHBF4– H2Se+

Scheme 10

(12)SeSe

Se

OHC

SeSe

SeOHC

toluene

reflux

OEt

OEt

+EtO

EtO

Bis"tri~uoromethyl# triselenocarbonate "19# has been prepared from 1\1\3\3!tetra~uoro!0\1!selenetane and B"SeCF2#2 "Equation "02## ð79ZN"B#415Ł[ Another less general triselenocarbonatepreparation involves the alkylation of barium triselenocarbonate "Equation "03## ð60CB0318Ł^however\ whether the structure of the product obtained is in fact a triselenocarbonate appears tobe questionable ðB!62MI 508!92Ł[

(20)Se

Se

F

FF

F

Se

F3CSe SeCF3

B(SeCF3)3+ (13)

(14)Se

SeMe

SeMe

BaCSe3 + 2 MeI

5[08[2[3 Selenocarbonyl Functions Flanked by Two Different Chalcogen Atoms\ RX"C1Se#YR

Compounds of this type are best prepared from intermediate diselenoxanthate salts[ For example\treatment of carbon diselenide with alkoxides and alkylation a}ords O!alkyl diselenocarbonates"10# "Scheme 00# ð69ACS1950Ł[ S!Alkyl derivatives "11# can be similarly prepared using thiolates"Scheme 01# ð69ACS1944Ł[

Se

RO Se–

Se

RO SeRRO– + CSe2

(21)

RX

Scheme 11


Se

RS Se–

Se

RS SeRRS– + CSe2

(22)

RX

Scheme 12

The cyclic selenocarbonate "12# can be prepared by treatment of 1!hydroxythiophenol with Viehe|ssalt\ followed by addition of sodium hydrogen selenide "Equation "04##[ The acyclic derivative "13#could be similarly prepared by consecutive treatment of Viehe|s salt with phenol and butanethiol\followed by sodium hydrogen selenide treatment "Equation "05## ð77AJC438Ł[

(15)SeO

Se

OH

SH

Me2N CCl2 Cl–++ NaHSe

(23)

(16)Me2N CCl2 Cl–Se

PhO SBu(24)

i, PhOH ii, BuSHiii, NaHSe+

Heterocyclic organometallic selenocarbonate derivatives such as "14# have been prepared byaddition of osmiumÐformaldehyde complexes to carbon diselenide "Equation "06## ð72JOM"133#C42Ł[Mixed selenocarbonates can also be metallated to more complex derivatives as previously described"Scheme 2# ð81JOM"316#102Ł[

(17)L2(CO)2OsO

OL2(CO)2Os

Se Se

CSe2

(25)

5[08[2[4 Selenocarbamates RO"C1Se#NHR\ RS"C1Se#NHR\ and RSe"C1Se#NHR

Monoselenocarbamates can be prepared by a variety of methods[ Treatment of an alcohol withan isoselenocyanate a}ords the corresponding selenourethane "15# in good yield "Equation "07##ð61BCJ1826Ł[ Addition of hydrogen selenide to an alkyl cyanate a}ords primary mono!selenourethanes "16# "Equation "08## ð55ACS1980Ł[ These compounds can also be prepared byammonolysis or hydrazinolysis of diselenocarbonates "Equations "19#\ "10## ð53ACS1306\ 69ACS1950\61ANY"081#090Ł[

(18)

Se

RHN OR1RNCSe + R1OH

(26)

(19)

Se

RO NH2(27)

ROCN + H2Se

(20)Se

RO NH2

Se

RO SeR1

NH3

(21)Se

RO NHNH2

Se

RO SeR1

NH2NH2

An aryl selenocarbamate "5# was the unexpected major product in the previously describedattempt to prepare a cyclic dioxygen!substituted selenocarbonate "Equation "6##[


Selenothiocarbamates "17# can readily be prepared by alkylation of thioureas\ followed by treat!ment of the intermediate salts with sodium hydrogen selenide under slightly acidic conditions"Scheme 02# ð58JOC2438Ł[ Under basic conditions the corresponding selenoureas are obtained "seebelow\ Equation "17##[

S

R2N NR2

SMe

R2N NR2

Se

R2N SMe

MeI

(28)

HSe–

pH 5–6+

Scheme 13

Reactions of carbon diselenide with secondary amines a}ord salts of diselenocarbamic acids "18#"Equation "11## ð56ACS1893\ 57ZC129\ 69ACS240\ 61IJS"A#022Ł[ Related salts can be prepared by thereaction of phosgeneiminium chloride with hydrogen selenide in the presence of triethylamine "seeabove\ Scheme 8#[ This route avoids the use of carbon diselenide ð79CC755A\ 79CC755B\ 75BCJ0630Ł[Such salts can readily be alkylated to the corresponding diselenocarbamates "29# "Equation "12##ð50JCS1811\ 75BCJ0630Ł[

2 R2NH + CSe2 R2NCSe2– R2NH2

+

(29)

(22)

(23)

(30)

N Se–

Se

NSe

Se

R

O

O

RBr

R

+

R

Salts of dialkyl selenocarbamates under mild oxidative conditions a}ord mixtures of bis"seleno!carbamoyl# selenides "21# and the corresponding triselenides "22# "Scheme 03# ð50JCS1811\69ACS848\ 71S660Ł[ This reaction proceeds through an intermediate unstable diselenide "20# that is inequilibrium with these species[ The monoselenide "21# can be converted to the triselenide "22# upontreatment with elemental selenium[ Conversely\ treatment of the triselenide with triethyl phosphitea}ords the monoselenide "Equation "13## ð71S660Ł[

Se

R2N SeSe NR2

Se

2 R2NCSe2– R2NH2

+[O]

(31)

2

Se

R2N Se NR2

Se

Se

SeSe

Se

Se

(32) (33)

+ R2N NR2

Scheme 14

Se

R2N Se NR2

Se

Se

SeSe

Se

SeR2N NR2

Se8

P(OEt)3

(32) (33)

(24)

Hydrazines react with carbon diselenide to a}ord diselenocarbazate salts "23# "Equation "14##ð55ACS1631Ł[ Nickel complexes of these compounds can be prepared but appear to have eneselenolatestructures such as "24# ð55ACS1631Ł[ The free diselenocarbazic acids "25#\ which can be prepared by


acidi_cation of the simple salts "Scheme 04#\ are reported in some cases to be more stable than thecorresponding dithiocarbazic acids ð69ACS848Ł[

Se

NH

Se–Me2HNMe2NNH2 + CSe2

+

(34)

(25)

Me2NN

SeH

Se Ni2

(35)

Se

MeNH2NMe Se–

Se

MeNHNMe SeH

(36)

MeNHNHMe + CSe2 +HCl

Scheme 15

Heterocyclic selenocarbamate derivatives*oxazolidine!1!selones "26#*have been prepared by avariety of routes[ Mercuric chloride!promoted reaction of 0\1!amino alcohols with carbon diselenidereadily a}ords this class of compounds in moderate yields "Equation "15## ð79JHC460\ 78H"17#158Ł[Another route to these compounds that avoids the problems associated with the use of carbondiselenide is outlined in Scheme 05 ð80JCS"P0#1384Ł[ This route allows a large!scale preparation ofchiral oxazolidineselones such as "27#\ useful as NMR shift reagents[ A more direct route tothese compounds involves metallation and direct selenation of the corresponding readily availableoxazolines "28# "Equation "16## ð80JOC5622Ł[

(26)

R2

NH2

R3

HO

R1

RO

N

R1

R

R3

R2Se+ CSe2

HgCl2

MeCN

(37)

H

NH2

Ph

HO NH2

Ph

TBDMS-O NH

Ph

TBDMS-O

OHC

TBDMS-Cl

TEA

HCO2H POCl3

N+

Ph

TBDMS-O N

Ph

TBDMS-O • SeNHO

Se

Ph(38)

Se0 tbaf

TBDMS = t-butyldimethylsilyl

Scheme 16

C–

ON

R R1

OHN

Se

R R1

i, base ii, Se0

iii, citric acid(27)


5[08[2[5 Phosphorus!substituted Selenocarbonyl Derivatives

Reaction of trialkylphosphines with carbon diselenide a}ords moderately stable zwitterionicselenocarbonyl compounds "39# "Equation "17## ð52ACS438\ 69QRS34Ł[ Complex reaction mixtureswere obtained using triphenylphosphine[

(28)Se

R3P Se–

R3P + CSe2 +

(40)R=Me, Et, Pr

5[08[3 FUNCTIONS CONTAINING AT LEAST ONE NITROGEN FUNCTION "AND NOHALOGEN OR CHALCOGEN FUNCTIONS#

5[08[3[0 Selenoureas "R1N#1C1Se

Selenoureas are probably the most widely studied selenocarbonyl derivatives[ The early chemistryassociated with the preparation and reactions of this class of compounds has been reviewedðB!62MI 508!95Ł[

Selenoureas can be prepared using a variety of general methods[ Thioureas can be converted toselenoureas "30# via an alkylationÐdisplacement sequence\ provided the pH is kept in the range 7Ð8"Scheme 06# ð52BSB038\ 58JOC2438Ł[ Reaction at a more acidic pH a}ords the selenocarbamateinstead "see Scheme 02#[ This route provides a convenient method for the preparation of both tri!and tetrasubstituted selenoureas[

S

Me2N NMe2

SMe

Me2N NMe2

Se

Me2N NMe2

MeI

(41)

NaHSe

pH 8–9

+I–

Scheme 17

Reaction of isoselenocyanates with ammonia\ primary amines\ or secondary amines providesanother general route to mono!\ di!\ or trisubstituted selenoureas "Equation "18## ð48M30\ 52JOC0531\52ZC237\ 56CB0262\ 56CB0348\ 79S59Ł[ Reaction of a primary ammonium salt with selenocyanate ionalso a}ords the monosubstituted selenourea "Equation "29## ð48G582Ł[

(29)

Se

RHN NR12

RNCSe + R12NH

(30)

Se

NH

NH2PhPhCH2NH3Cl– + KSeCN

+

Carbodiimides react with hydrogen selenide to a}ord 0\2!disubstituted selenoureas "Equation"20## ð42JOC181Ł[ Cyanamides also react with H1Se to a}ord unsubstituted\ mono! or 0\0!di!substituted selenoureas "Equation "21## ð36JA0722\ 40JA0753\ 42JOC181\ 52OSC"3#248Ł[

Se

RHN NHRRN • NR + H2Se (31)

Se

R2N NH2

R2N N (32)+ H2Se

Cyanamide and cyanamide salts are reported to react with phosphorus pentaselenide in aqueoussolution\ presumably via formation of H1Se\ to a}ord selenourea "Equation "22## ð80EGP180641Ł[Phosphorus pentaselenide is reported to convert urea into selenourea in only poor yield "Equation


"23## ð55ACS170Ł[ N\N!Dimethylcyanamide is also reported to react with another selenating reagent\bis"trimethylsilyl# selenide\ to a}ord 0\0!dimethylselenourea in low yield "Equation "24## ð89CL0392Ł[

Se

H2N NH2N +H2N

H2O

50–100 °C(P2Se5)n (33)

(34)

Se

H2N NH2

O

H2N NH2

(P2Se5)n+

(35)

Se

Me2N NH2

NMe2N + (TMS)2Se

Treatment of dibenzyl triselenocarbonate "31# with excess primary amine a}ords symmetrical0\2!disubstituted selenoureas\ presumably via an isoselenocyanate intermediate "32# "Scheme 07#ð61ANY"081#090Ł[ Treatment of carbon diselenide with excess primary amine also a}ords a 0\2!di!substituted selenourea ð25CB0245Ł[ This reaction also probably involves an isoselenocyanate inter!mediate "Scheme 08#[

Se

Se Se PhPh

Se

Se NHRPh+ RNH2

(42)

–PhCH2SeH

RN • SeSe

RHN NHR(43)

RNH2

Scheme 18

Se

RHN Se– RNH3RNH2 + CSe2

–RNH3SeH+

+ –

RN • Se

Se

RHN NHR

RNH2

Scheme 19

Tetrasubstituted selenoureas can be prepared from selenocarbamoyl selenides or triselenides "33#"see Scheme 03# by treatment with secondary amines at elevated temperature in the presence ofoxygen "Equation "25## ð71S660Ł[

(36)Se

R2N Sen

Se

R2N NR2

2 R2NHO2

70 °C+

2

n = 1, 3(44)

Selenobiurets "34# can be prepared from the corresponding thiocarbonyl analogs by an alkylationÐselenation procedure similar to that used for the preparation of simple selenoureas "Equation"26##[

(37)

X = O, S, Se

S

H2N NH

NH2

X Se

H2N NH

NH2

X

(45)

i, MeI

ii, NaHSe


Heterocyclic selenoureas such as selenopyrimidines "35# and selenobarbiturates "36# have beenprepared from selenourea and b!dicarbonyl compounds "Equations "27# and "28## ð45JA4181\48JA5169Ł[

(38)

ONaR

EtO2CHN

NH

O

R

Se

selenourea

(46)

(39)HN

NH

O

Se

R

R

O

(EtO2C)2CR2selenourea

(47)

Metallation of N!methylimidazole at low temperature followed by selenation with elementalselenium a}ords the selenium analogue "37# of the antithyroid drug MMI "Equation "39##ð83JOC3580Ł[

(40)N

NN NH

SeMe

Me

(48)

i, BuLi, –78 °C

ii, Se0

iii, H+

Selenosemicarbazides "38# can be prepared by reaction of an isoselenocyanate with a hydrazine"Equation "30## ð51BSB430\ 55ACS167\ 56CB0262Ł[ These compounds can be converted to the cor!responding selenosemicarbazones ð45JA86\ 51BSB430\ 55ACS167\ 56CB0262Ł[

(41)

Se

RHN NH

HN

R1

(49)

RNCSe + R1NHNH2

Other biologically interesting complex selenocarbonyl derivatives have also been prepared viadisplacements using selenourea[ These include the selenium analogue of the benzodiazepin drug{{TIBO|| "49# "Equation "31## ð80JMC2076Ł and selenoguanosine derivatives "40# and "41# "Scheme19# ð80TL3712Ł[ The latter compound is formed via a novel polyhetero!Claisen rearrangement[Finally\ tris"methylphenylamino#methane "42# reacts with elemental selenium to a}ord the cor!responding selenourea in good yield "Equation "32## ð76CB0470Ł[

NN

NH

Cl

N

HN

NH

Se

Se

H2N NH2(42)

(50)

(43)

Se

N NPhPh

Me Me

HC N

Me

Ph

+ Se°220 °C

melt

(53)

3


(51)

HN

N N

N

O

O

Br

H2N

OH

OH

HO

HN

N N

HN

O

O

Se

H2N

OH

OH

HO

Se

H2N NH2

Br

+

HN

N N

N

O

O

Se

H2N

OH

OH

HO

HN

N N

N

O

O

Se

H2N

OH

OH

HO

heat

(52)

Scheme 20

5[08[3[1 Telluroureas "R1N#1C1Te

Cyclic telluroureas "44# have been prepared by tellurium!promoted cleavage of the tetra!aminoethylene derivatives such as "43# "Equation "33## ð79CC524Ł[ A variety of metal penta!carbonyl complexes of these compounds "46# have also been prepared by treatment of thetelluroureas with the metal isonitrile pentacarbonyl complex "45# "Equation "34## ð79CC524Ł[

(44)N

N N

N

R

R R

R

TeN

N

(55)(54)

2 Te

∆

R = Me, Et

R

R

(45)TeN

N

Et

Et

TeN

N

Et

Et

M(CO)5

(56) (57)

+ M(CO)5(NCMe)

M = Cr, W, Mo

Tellurium is also reported to react with 0\2!dimethylbenzimidazoline at elevated temperature toa}ord the corresponding cyclic tellurourea "47# "Equation "35## ð58ZOB830Ł[

(58)

(46)TeN

N

Me

Me

N

N

Me

Me

2 Te

∆


6.20Functions Containing anIminocarbonyl Group and atLeast One Halogen; AlsoOne Chalcogen and NoHalogen

THOMAS L. GILCHRISTUniversity of Liverpool, UK

5[19[0 FUNCTIONS CONTAINING AT LEAST ONE HALOGEN 591

5[19[0[0 Iminocarbonyl Halides with Two Similar Haloèn Functions 5915[19[0[0[0 Carbonimidic di~uorides\ F1C1NR 5915[19[0[0[1 Carbonimidic dichlorides\ Cl1C1NR 5935[19[0[0[2 Carbonimidic dibromides\ Br1C1NR 5095[19[0[0[3 Carbonimidic diiodides\ I1C1NR 501

5[19[0[1 Iminocarbonyl Halides with Two Dissimilar Haloèn Functions 5015[19[0[1[0 Carbonimidic chloride ~uorides\ ClFC1NR 5015[19[0[1[1 Carbonimidic bromide ~uorides\ BrFC1NR 5025[19[0[1[2 Carbonimidic bromide chlorides and carbonimidic chloride iodides\ ClXC1NR "X�Br or I# 502

5[19[0[2 Iminocarbonyl Halides with One Haloèn and One Other Heteroatom Function 5035[19[0[2[0 Iminocarbonyl ~uorides with one other heteroatom function 5035[19[0[2[1 Iminocarbonyl chlorides with one other heteroatom function 5055[19[0[2[2 Iminocarbonyl bromides and iodides with one other heteroatom function 512

5[19[1 FUNCTIONS CONTAINING AT LEAST ONE CHALCOGEN "AND NO HALOGENS# 512

5[19[1[0 Iminocarbonyl Compounds with Two Similar Chalcoèn Functions 5125[19[1[0[0 Iminocarbonyl compounds with two oxyèn functions 5125[19[1[0[1 Iminocarbonyl compounds with two sulfur functions 5155[19[1[0[2 Iminocarbonyl compounds with two selenium functions 517

5[19[1[1 Iminocarbonyl Compounds with Two Dissimilar Chalcoèn Functions 5175[19[1[1[0 Iminocarbonyl compounds with one oxyèn and one sulfur function 5175[19[1[1[1 Iminocarbonyl compounds with one oxyèn or sulfur and one selenium or tellurium function 529

5[19[1[2 Iminocarbonyl Compounds with One Chalcoèn and One Other Heteroatom Function 5205[19[1[2[0 Iminocarbonyl compounds with one oxyèn and one nitroèn function 5205[19[1[2[1 Iminocarbonyl compounds with one oxyèn and one phosphorus function 5235[19[1[2[2 Iminocarbonyl compounds with one oxyèn and one metalloid or metal function 523

5[19[1[3 Iminocarbonyl Compounds with One Sulfur and One Other Heteroatom Function 5235[19[1[3[0 Iminocarbonyl compounds with one sulfur and one nitroèn function 5235[19[1[3[1 Iminocarbonyl compounds with one sulfur and one phosphorus function 5255[19[1[3[2 Iminocarbonyl compounds with one sulfur and one metalloid or metal function 526

5[19[1[4 Iminocarbonyl Compounds with One Selenium and One Other Heteroatom Function 526

590

591 Iminocarbonyl and Haloèn or Chalcoèn

5[19[0 FUNCTIONS CONTAINING AT LEAST ONE HALOGEN

5[19[0[0 Iminocarbonyl Halides with Two Similar Halogen Functions

In the mid!0889s these iminocarbonyl halide compounds XYC1NR "X\ Y�halogen# are namedin Chemical Abstracts as carbonimidic dihalides^ they are also commonly called isocyanide dihalides[Methods of synthesis of compounds of this type have been reviewed previously[ The most importantof these reviews are by Ulrich ðB!57MI 519!90Ł\ by Ulrich and Richter ðB!66MI 519!90Ł\ by Ku�hle etal[ ð56AG"E#538\ B!60MI 519!90Ł and by Ku�hle ð72HOU"E3#411Ł[ The reviews by Ulrich and those byKu�hle and colleagues all contain experimental details for the preparation of some compounds ofthis class[ Several speci_c compounds containing ~uorine are covered in appropriate sections of theGmelin Handbooks on per~uorohaloorganic compounds ðB!68MI 519!90\ B!79MI 519!90\ B!70MI 519!90Ł[

5[19[0[0[0 Carbonimidic di~uorides\ F1C1NR

Carbonimidic di~uoride compounds have been reported with R�H\ D\ alkyl\ perhaloalkyl\ aryl\hetaryl\ acyl! and with a variety of heteroatomic substituents on nitrogen[ No methods exist whichcan be used to prepare all these types of compound but there are methods which have somegenerality\ these are listed below[ Methods which are speci_c to derivatives of one type are describedfor the compounds concerned[

"i# From tri~uoromethylamines\ F2CNHR

Tri~uoromethylamines serve as precursors to carbonimidic di~uorides of various types\ includingthe parent compound "R�H#[ Conditions and reagents used to bring about the dehydro~uorinationvary depending upon the substituent\ but low temperatures are desirable because several types ofcarbonimidic di~uoride dimerise easily at ambient temperatures[ Triethylamine and potassium~uoride have been used most often as co!reagents[

Examples of carbonimidic di~uorides which have been prepared by this method are listed inTable 0[

Table 0 Carbonimidic di~uorides formed by dehydro~uorination of tri~uoramines\ F2CNHR[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

YieldR Reaènts and conditions ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐH NEt2\ 084Ð152 K 77CC094CF2 NaF\ 039>C 69 48JGU1551Ph KF\ 039>C 48JGU1551 B!60MI 519!90C5H3Cl!3 NEt2\ MeCOCl\ 39>C 27 B!60MI 519!90OMe\ OBut\ OCF2 KF\ −085Ð13>C 70JFC"07#330OCF1CF2 KF\ −085Ð13>C 81 89EUP242632*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

"ii# From carbonimidic dichlorides

Some carbonimidic dichlorides have been converted into the corresponding di~uorides[ Tri!~uoroamines can be intermediates\ so that in such examples the method is an extension of method"i#[ This is illustrated by the reaction of N!arylcarbonimidic dichlorides with hydrogen ~uoride togive N!aryltri~uoroamines which are then dehydro~uorinated by heating with potassium ~uoride"Scheme 0# ð55AG"E#737\ B!60MI 519!90Ł[ Aromatic carbonimidic dichlorides can also be convertedinto the di~uorides by heating with an alkali metal ~uoride in a high boiling inert solvent^ forexample\ N!pentachlorophenylcarbonimidic di~uoride is obtained from the dichloride and pot!assium ~uoride in 57) yield ðB!60MI 519!90Ł[ Related preparations of compounds F1C1NXF4

"X�S or Te# have been described starting from the corresponding carbonimidic dichlorides "Scheme


1# "X�S] ð65IC03\ 77IC469Ł\ X�Te] ð74IC3060Ł# and the azine F1C1NN1CF1 has been preparedby heating the corresponding tetrabromide with silver ~uoride ð51JOC1478Ł[ F1C1NCF2 is preparedin good yield by heating Cl1C1NCCl2 with an excess of sodium ~uoride in sulfolane ð61GEP1090096Ł[

NR

Cl

Cl

NR

F

F

F

F

FHF

Scheme 1

NHR

Scheme 2

NXF5

Cl

Cl

NXF5

F

FHgF2

heat

CF3

Hg N

XF52

"iii# From isothiocyanates

The conversion of several aryl isothiocyanates into carbonimidic di~uorides has been achievedby reaction with mercury"II# ~uoride and other metal ~uorides ð54JA3227Ł[ N!Ethylcarbonimidicdi~uoride was also prepared "26)# by this method[

"iv# From isocyanides

The reaction of isocyanides RNC "R�But\ Ph\ 1!ClC5H3\ and 1!FC5H3# with ~uorine at −67>Cleads to the formation of the corresponding carbonimidic di~uorides ð79TL3782Ł[

"v# Dehalo`enation methods

The best methods for the preparation of the N!halocarbonimidic di~uorides start from nitriles[An e.cient synthesis of the N!chloro compound is shown in Scheme 2 ð72JOC3733Ł and the N!~uoroanalogue can be prepared in a related way by dechlorination of ClCF1NClF with mercury intri~uoroacetic anhydride ð70JOC0166\ 73IC1077Ł[ Several N!per~uoroalkyl compounds\ includingF1C1NCF2 and F1C1NCF1CF1N1CF1\ have been made by a related photochemical dechlori!nation method ð89IC460Ł[ N!Bromocarbonimidic di~uoride is prepared from cyanogen ~uoride\bromine and potassium ~uoride ð73JA3155\ 77JOC3332Ł[ The reaction of "CF2#1NX "X�Br or Cl#with iron pentacarbonyl leads to the formation of F1C1NCF2 in high yield ð54JCS4663Ł[

A related reductive method has provided a route to carbonimidic di~uorides "0# "Equation "0##[The reaction of chlorodi~uoronitrosomethane with diethyl phosphite gave "0# "31)# ð58JGU0583Ł[

Scheme 3

NCl

F

F

F

Cl

FClF

85%NCl

135 °C

85%NCl2

N

F

F

P

EtO

H(1)

O P

OEt

O

OEt

O

F

Cl

N O +F42%

EtO

(1)

"vi# Speci_c methods

Some methods which are useful for speci_c derivatives or for speci_c groups of compounds arediscussed under this heading[


The hydrolysis of tri~uoromethyl isocyanate in triethylamine has been used to prepare car!bonimidic di~uoride^ F1C1ND has also been made in this way ð81ZN"B#240Ł[ Among the manymethods which can be used to prepare N!tri~uoromethylcarbonimidic di~uoride ðB!68MI 519!90Ł\several involve the vapour phase pyrolysis of copolymers of tri~uoronitrosomethane and per!haloalkenes ð44JCS0770\ 53JCS0240\ 54JCS5198\ 80MI 519!90Ł[ The compound can also be formed bydecomposition of "CF2#1NOSN ð75JFC"23#35Ł[ The vapour phase pyrolysis of oxazetidines "1#^R�CF2\ C1F4 and C2F6# also provides a route to the corresponding per~uoroalkylcarbonimidicdi~uorides "Equation "1## ð45JCS2305\ 53JCS0240\ 53JCS3955Ł[ The imine "CF2#1C1NCF2 is isomerisedto F1C1NCF"CF2#1 by heating with caesium ~uoride as a catalyst ð80JFC"42#070Ł[

(2)NR

F

F

O N

FF F

F

R(2)

The pyrolysis of di~uorodiazirine provides a route to F1C1NN1CF1 ð57JHC30\ 73USP3335957Ł[Perhaloalkenes can be inserted into the N0N bond of this azine by irradiation of the mixtureto give new carbonimidic di~uorides "for example\ the compound F1C1NCF1CF1N1CF1 fromtetra~uoroethylene# ð56JA2757Ł[ The hydrazone "2# has been isolated from the photolysis of theazoalkane "3#^ the reaction sequence shown in Scheme 3 can account for its formation ð89JOC0492Ł[

N

F

F

N

Et

F

F

NF

N

HN

F

F

N

Et

F

(3)

F

F

NF

N

•

•

(4)

RH

Scheme 4

5[19[0[0[1 Carbonimidic dichlorides\ Cl1C1NR

The dichlorides are by far the most numerous of the carbonimidic dihalides^ a few compounds ofthis class have been identi_ed as natural products ð66JA6256\ 67TL0280\ 67TL0284Ł and there are severalwell!established methods of synthesis of dichlorides bearing a wide variety of functional groups onnitrogen[ The review by Ku�hle ð72HOU"E3#411Ł provides a valuable survey of the literature up to0871^ this and the earlier review by Ku�hle et al[ ðB!60MI 519!90Ł contain experimental details ofpreparations and tables of examples which are not readily accessible from other sources[ The majormethods of preparation are detailed below and\ where appropriate\ examples of their use are quoted\particularly when the original paper gives experimental details[

"i# From isothiocyanates

The oldest method of preparation is from isothiocyanates] it is known for alkyl!\ aryl!\ acyl!\phosphoryl! and sulfonyl!substituted carbonimidic dichlorides[ The chlorination of alkyl and acylisothiocyanates is usually carried out with chlorine in an inert solvent and the products cansometimes be isolated in good yield\ for example R�Me\ 74) ð48JGU1020Ł^ R�Ph\ 85) ðB!60MI519!90Ł^ R�b!tetraacetylglucosyl\ 81) ð76AG"E#248Ł[ The method is not completely general] theproducts can be unstable "as with 1!nitrophenyl isothiocyanate# or they can undergo further reactionwith chlorine "e[g[\ reaction of phenyl isothiocyanate with an excess of chlorine in chloroform resultsin further chlorination at the 3!position of the ring ð53JOC0502Ł#[ The course of the reaction ofchlorine with isothiocyanates is shown in Scheme 4\ the intermediate sulfenyl chlorides "4# havingbeen isolated in a few cases[

Scheme 5

NR

Cl

Cl

Cl

ClS

NRCl2

S•RN

(5)


Acyl isothiocyanates can be chlorinated in much the same way\ with chlorine in an inert solventðB!60MI 519!90\ 64JCS"P1#0935Ł[ A Lewis acid catalyst facilitates the reaction and both aluminium"III#chloride and titanium"IV# chloride have been used[ An example of the e}ect of a catalyst is shownin Scheme 5[ Chlorination of carbonyl diisothiocyanate "5# in the absence of a catalyst gave thecarbonimidic dichloride "6# but in the presence of iodine both functional groups were chlorinatedto give "7# ð71CB2476Ł[ The thiocyanato group of carbonyl isocyanate isothiothiocyanate "8# hasalso been selectively chlorinated to give compound "09# in good yield^ the isocyanate function canthen be selectively hydrolysed ð70CB1953Ł[

N •

•N

O

S

S

N

•N

O

S

Cl

Cl

Cl

ClN

N

O

Cl

Cl

Cl2

82%

H2O

quant.N •

•N

O

S

O

(9)

N

•N

O

O

(6)

Cl

Cl

(7)

(10)

N

NH2

O

Cl2

68%

(8)

Cl

Cl

78%

Cl2, I2(cat.)

Scheme 6

Phosphoryl isothiocyanates are similarly readily chlorinated but the chlorination of sulfonylisothiocyanates is more sluggish[ An alternative is to use related reagents such as the dithiocarbamatesalts "00# ðB!60MI 519!90Ł or the corresponding bismethyl compounds "01# ð72AQ"C#004Ł\ both readilyavailable from the corresponding sulfonamide[ Both are more readily chlorinated than the iso!thiocyanate[ The benzothiazolyl!substituted carbonimidic dichloride "02# has been obtained "54)#in an analogous manner by chlorination of the corresponding bis"methylthio# compound ð73S419Ł[The _nal product of chlorination of trimethylsilyl isothiocyanate is the sulfenyl chloride Cl1C1NSClðB!60MI 519!90Ł[

NSO2Ar

Na+ –S

Na+ –S

(11)

NSO2Ar

MeS

MeS

(12) (13)

NS Cl

N

Cl

Cl

"ii# From isocyanides

The addition of chlorine to isocyanides in the cold is also a long!established method for thepreparation of carbonimidic dichlorides[ It has been used mainly for alkyl derivatives\ for exampleR�But\ 41) ðB!60MI 519!90Ł\ R�TsCH1\ 56) ð70JHC0016Ł and R�PhCH1\ 57) ð75T1566Ł[ Arylderivatives can also be prepared by this method and because of the mild reaction conditions it canbe useful for the preparation of compounds which are sensitive to further chlorination ð76CB310Ł[A speci_c preparation based on an isocyanide is the formation of chromium carbene complexes by


reaction of coordinated trichloromethyl isocyanide with secondary amines "Equation "2##ð77AG"E#0233\ 78CB0896Ł[

R2N

N

Cl

Cl

: Cr(CO)5Cl3CNCCr(CO)5

R2NH

17–73%(3)

"iii# From formanilides

Many N!arylcarbonimidic dichlorides have been prepared in good yield from the correspondingformanilides by chlorination in thionyl chloride as a solvent "Equation "3## ð51AG"E#536\ B!60MI 519!90Ł[ Sulfuryl chloride is most often used as the chlorinating agent[ The method is most e.cient foraryl derivatives with deactivating groups on the ring which inhibit ring chlorination[ Examples frommore recent literature include preparation of the 2!tri~uoromethylphenyl derivative ð76JCS"P0#0958Ł\the 3!cyanophenyl derivative ð81SC0080Ł and the 1\5!dichloro!3!nitrophenyl derivative ð76JMC0130Ł[

ArN

Cl

ClArNHCHO

SO2Cl2, SOCl2(4)

An example of the use of an analogous procedure for the preparation of an aliphatic carbonimidicdichloride is the preparation of Cl1C1NCH1CH1CN by chlorination of the corresponding for!mamide ð68GEP1642193\ 68GEP1643593Ł[

"iv# From isocyanates

The reaction of several aliphatic isocyanates with chlorinating agents such as phosphorus penta!chloride is reported to give N!alkylcarbonimidic dichlorides[ For example\ methyl isocyanate ðB!57MI 519!90Ł and butyl isocyanate ðB!60MI 519!90Ł have been converted into the correspondingdichlorides "in 72) and 49) yields# by reaction with a mixture of phosphorus pentachlorideand phosphorus oxychloride[ The method is not a useful one for aryl derivatives because at thetemperatures required for reaction phosgene is eliminated[ However\ there are examples of successfulchlorination of phosphoryl and sulfonyl isocyanates ðB!57MI 519!90Ł[

Some a!chloroalkyl isocyanates exist in tautomeric equilibrium with carbonimidic dichlorides[For example\ trichloromethyl isocyanate is in equilibrium with the chloroformyl derivative "03#"Scheme 6# and reaction of the mixture with antimony penta~uoride gave the ~uoride "04# as themajor product ð77ZOB0405Ł[ Compound "03# is reported as the product of radical chlorination ofmethyl isocyanate ð74GEP2226828Ł^ it can be prepared in the laboratory by Curtius rearrangementof trichloroacetyl azide ð82T2116Ł[

SbF5

65%•N O

(14)F

N

O

(15)

Cl

Cl

Scheme 7

Cl

N

O

Cl

Cl

Cl

ClCl

"v# From cyano`en chloride

Cyanogen chloride is a very useful starting material for the preparation of a variety of car!bonimidic dichlorides[ Examples of several types which can be prepared from cyanogen chlorideare given in Table 1[ Reaction of cyanogen chloride with chlorine in the presence of alkenes leadsto the formation of N!"b!chloroalkyl#carbonimidic dichlorides "Equation "4## ð58JPR04\ 69S19Ł[These {three component| reactions may go by way of Cl1C1NCl since this compound has been


shown independently to add to the double bond of alkenes ð58AG"E#595Ł[ A tetramer of cyanogenchloride\ prepared in the presence of hydrogen chloride and DMF\ has also been shown to be acarbonimidic dichloride "05# ðB!60MI 519!90Ł[

N

N

N

Cl

Cl

N

Cl

Cl

(16)

R

N

Cl

Cl

Cl

Cl NCl2,

R (5)

Table 1 Carbonimidic dichlorides prepared from cyanogen chloride\ ClCN[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

YieldR Rea`ents and conditions ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐCH1OMe MeOCH1Cl\ 49>C\ 4 atm 09 55AG"E#734CH1CH1Cl Cl1\ H1C1CH1\ 9>C 08 58JPR04CH"Cl#CH1Cl Cl1\ H1C1CHCl\ FeCl2 89 69S19But Cl1\ ButCl\ FeCl2 80 62T186MeC1CHCl Cl1\ H1C1C"Cl#Me\ FeCl2 59 69S19COCH1Cl ClCH1COCl\ 49>C\ 4 atm 53 55AG"E#734COPh PhCOCl\ 49>C\ 4 atm 19 55AG"E#734Cl Cl1\ 59>C\ carbon 62 58AG"E#595\ 76JFC"26#18SCl SCl1\ 9>C 16 47JCS653S"CF2#SF3 CF2SF3Cl\ hn 39 65IC03TeF4 TeF4Cl\ hn 21 74IC3060N"CF2#1 "CF2#1NCl\ hn 099 55JCS"A#822\ 81IC377N"CF2#C1F4 CF2"C1F4#NCl\ hn 59 78IC2234*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

"vi# Other chlorination methods

There are several useful examples of the formation of carbonimidic dichlorides by chlorinationof amines and amides\ but none of the reactions is general[ Reaction of N\N!dimethylaniline withchlorine under carefully controlled conditions leads to the formation of the carbonimidic dichloride"06# in high yield ð51AG"E#521Ł[ Other examples of chlorination routes are shown in Scheme 7ð58LA"629#022\ 67CB0508\ 72MI 519!90Ł[

N

Cl

Cl

(17)

Cl

Cl

Cl

Scheme 8

N

CCl3

Cl

Cl

R

N

O

Cl

ClR

MeHN O

Cl

Me2N O

Cl2, hν

Cl2, heat


An important chlorination reaction is the reaction of glyoxylic acid aldoxime to give N!hydroxy!carbonimidic dichloride "Scheme 8#[ The chlorination has been carried out with chlorineð77SC0060Ł and also with N!chlorosuccinimide or t!butyl hypochlorite ð78LA874Ł[ "This oxime canalso be prepared by reductive methods ðB!60MI 519!90Ł^ e[g[\ it has been prepared by the reductionof trichloronitromethane with tin and HCl ð74USP3447059Ł[# The chlorination of glyoxylic acidaldoxime has an analogy in the formation of the hydrazone "07#\ a possible mechanism for whichis shown ð61JOC1994Ł[

N

OH

HO2C

N

OH

Cl

Cl

Cl

Cl

Cl

Cl2

(18)

Ar =

N

NHAr

HO2C

Cl

N

NHAr

Cl

Cl

Scheme 9

N

O H

NO Ar

ClCl

"vii# Methods involvin` introduction of the CCl1 fra`ment

Dichlorocarbene can be transferred to a variety of nitrogen compounds to produce carbonimidicdichlorides ð61TL2716\ 62ZOR0648\ B!66MI 519!90Ł[ Some of these reactions are outlined in Scheme 09ð57CC857\ 60JOC0675\ 62JA1871\ 72JPR676\ 81TL1228Ł[ The reaction of azidooctane with dichlorocarbeneappears to be capable of extension to the preparation of other carbonimidic dihalides[

NPri

Cl

Cl

NPriPriNNPri•PriN

Cl

Cl

N

Cl

Cl

Ph

+

NPh

NPh

Cl

Cl

–

Scheme 10

41%

63%

N

C8H17

Cl

Cl

PhHgCCl2Br

PhHgCCl3

n-C8H17N3

CHCl3, NaOH

39%

–

N

(CH2)2C4F9

Cl

Cl

+

CHCl3, KOBut

89%

C4F9(CH2)2N3

There are also some useful speci_c syntheses based on the formal transfer of CCl1 from tetra!chloromethane[ The hydrazone "08# has been synthesised by methods involving the low temperaturereaction of tetrachloromethane with the azosilane "19# and with salts of silylated hydrazinesð60CB2878\ 65ZN"B#0206\ 75JOM"290#04\ 80ZAAC"594#020Ł[ These reactions probably involve


dichlorocarbene as an intermediate since compound "08# is also formed from "19# and a di}erentsource of dichlorocarbene "Equation "5##[

N

N(TMS)2

Cl

Cl

N N

TMS

TMSCCl4, –78 °C

or CHCl3, (TMS)2N–Na+

70%(6)

(20) (19)

Some per~uoroaryl! and perchloroaryl!carbonimidic dichlorides can be synthesised by the reac!tion of the perhaloamine with tetrachloromethane and aluminium"III# chloride ð72JFC"11#328\72KGS687Ł and the same procedure has been used to convert penta~uorophenylhydrazine into thehydrazone "10# "Equation "6## ð75ZOR0186Ł[ N!Phenylcarbonimidic dichloride is one of the productsof photolysis of mixtures of aniline and tetrachloromethane or chloroform ð78ZN"B#0478Ł andpenta~uorophenylcarbonimidic dichloride is produced by the vapour phase pyrolysis of chloroformwith penta~uoroaniline ð66JFC"8#494Ł[

N

Cl

Cl3C

N C6F5

Cl

(21)

C6F5NHNH2

CCl4, AlCl3

49%(7)

"viii# From other carbonimidic dichlorides

Carbonimidic dichlorides with reactive functional groups attached to nitrogen can be convertedinto other carbonimidic dichlorides and in some cases this provides the best route to the new species[The addition of N!chlorocarbonimidic dichloride to carbonÐcarbon double bonds has been referredto earlier^ this compound also reacts with sulfur\ in a process catalysed by chloride ions ð63TL0576Łand with dimethyl or diphenyl disul_de "Scheme 00# ð63TL0580Ł[ The sulfenyl chloride Cl1C1NSCl\like other sulfenyl halides\ adds readily to alkenes] the adduct with cyclohexene has been isolatedin 79) yield ð47JCS653Ł[ New acylcarbonimidic dichlorides can also be formed from Cl1C1NCOCl\an example being the generation of the phosphorus!containing species "11# "Equation "7##ð67JGU0401Ł[

N

Cl S N

Cl

S8, Cl–

NCl

Cl

Cl

NSCl +Cl

Cl

NSPh

Cl

Cl

Cl

Cl

PhSSPh

90%

50% 30%

Scheme 11

N

Cl

O

N

ClP CCl3

Cl CCl3N

Cl

O

Cl

Cl

NHP

Cl

Cl3C

+ Cl3C

(22)

(8)

"ix# Methods for dichloroiminium cations

Salts of the type "12^ R0\ R1�alkyl# are very useful synthetic intermediates[ The methods ofpreparation and their chemistry have been reviewed by Janousek and Viehe ðB!65MI 519!90Ł and


by Marhold ð72HOU"E3#544Ł[ No new general preparative methods have been reported since thepublication of these reviews[ The most important methods are all of a similar type\ involving thechlorination of compounds of general structure "13^ X�H\ Cl\ SR or SO1R# "Equation "8##ð60ZOR1973\ 62ZOR28\ B!65MI 519!90Ł[ Salts derived from cyclic secondary amines have been synthesisedby reaction with carbon disul_de followed by chlorination ð78SC1714Ł[ On heating to 039>C theyundergo ring opening to carbonimidic dichlorides "Equation "09##[

(9)N

ClR2

Cl

S

R1R2N X

(23)

Cl2, PCl5R1

(24)

Cl–+

ClX

N ClNX

Cl

Cl

Cl

Cl–

140 °C

77–86%(10)

+

There are a few examples of the preparation of dichloroiminium salts "12# by N!alkylation ofcarbonimidic dichlorides ðB!65MI 519!90\ 81ZAAC"506#025Ł but this is not a general method since thecarbonimidic dichlorides are poor nucleophiles[ The compound Cl1C1NCl can be protonated in asuperacid medium ð81ZAAC"506#025Ł[ The parent dichloroiminium cation Cl1C1NH1

¦ has beengenerated from cyanogen chloride and hydrogen chloride and both tetrachloroferrate and hexa!chloroantimonate salts have been isolated ð62T186Ł[ A review of conjugated iminium salts "14#\which are prepared from a variety of chloroiminium salts and nitriles R0CN\ includes examples ofdichloroiminium salts "14^ R0�Cl# ð77S544Ł[

Cl N NR32 X–

R1 R2

(25)

+

A compound which can formally be regarded as a coordinated dichloroiminium cation is thedichlorodiazomethane complex "15#\ which has been generated from a structurally related diimidecomplex by CCl1 transfer ð79CC768\ 70JCR"S#165Ł[ The salt ð"CO#4Cr1C1N¦

1CCl1Ł AlCl3− has beenisolated from the reaction of the isocyanide complex "CO#4CrCNCCl2 with aluminium trichlorideð75OM1076Ł[

(26)

Cl

N Cl

N+

Br

WP

PP

P

P

P= dppe

5[19[0[0[2 Carbonimidic dibromides\ Br1C1NR

The methods available for the synthesis of carbonimidic dibromides are nearly all analogous tomethods used for the corresponding dichlorides\ but with fewer examples[

The most straightforward method of preparation is the addition of bromine in the cold toisocyanides\ a method which was _rst described in 0767 ð0767BSF"1#074Ł[ Experimental details havebeen given for the preparation "65)# of N!phenylcarbonimidic dibromide by this method ðB!60MI519!90Ł and the thermally unstable N!cyclohexyl analogue has been prepared in the same way[The low stability of simple N!alkyl derivatives can preclude their full characterisation[ Similarly\Br1C1NCN\ prepared by the addition of bromine to isocyanogen\ is unstable and polymeriseseasily ð82JOC5829Ł[

N!3!Bromophenylcarbonimidic dibromide is reported to be formed by bromination of phenyl!


thioformamide "Scheme 01# ð50MI 519!90Ł[ Other methods for the formation of N!aryl derivativeswhich are analogous to those used for carbonimidic dichlorides are also illustrated in Scheme 01ð68BSF"1#419\ 77CB0334Ł[

NHPh

S

N

Br

Br

Br

NC6F5

Br

BrC6F5NH2

MeO

Cl

Cl

N • OPhNMe3, Br3

+ –

NAr

Br

Br

CBr4, AlBr3

21%

Scheme 12

The bromination of methyl isocyanate with N!bromosuccinimide leads to the formation oftribromomethyl isocyanate "16a# "59)# ð71CB759Ł[ Like the corresponding trichloromethyl iso!cyanate this compound exists in equilibrium with a carbonimidic dihalide isomer "16b# "Equation"00##[ N!Tri~uoromethylcarbonimidic dibromide has been prepared by the reaction of the amine"CF2#1NH with boron tribromide ð73JFC"13#412Ł[

(11)N

Br

Br

O

Br

N

Br

Br

Br

(27a) (27b)

•

O

The best route to the oxime "17#\ a useful precursor to bromonitrile oxide\ is the bromination ofglyoxylic acid aldoxime "Equation "01##[ This reaction has been carried out using N!bromo!succinimide ð78LA874Ł and with bromine in water ð89JOC2934\ 81TL2002Ł[ The preparation has beenperformed on a 499 g scale ð73TL376Ł[ The oxime can be acylated on oxygen to give other car!bonimidic dibromides ð76EUP121901Ł[ There are also related bromination routes to the arylhy!drazones "18# ð61JOC1994\ 65CI"L#053Ł and to the N\N!dimethylhydrazone ð80ZOR422Ł[

(12)N

Br OH

Br

(28)

Br2, H2O

47%N

OH

HO2C

N

Br NHAr

Br

(29)

The bromination of tetrazolylhydrazones "29# has provided a route to several azines "20# whichhave been isolated in moderate to good yield "Equation "02## ð53CI"L#0646\ 68JCS"P0#613Ł[ The tetra!bromoazine "21# has been prepared by an analogous route ðB!60MI 519!90Ł[

(13)N

Br N

Br

(30)Ar

NN

NNH

NH

N Ar

(31)

Br2, AcOH


N

Br N

Br

Br

Br

(32)

Dibromoiminium salts Br1C1NR1¦Br− "R�Me or Et# have been prepared by routes analogous

to those used for the dichloroiminium salts ð63ZOR338\ 77AJC452Ł[ Thus\ the dimethyliminium saltwas formed by bromination of the disul_de "22# "Equation "03##[

Me2N SS NMe2

S

S

NMe2 Br–

Br

Br+Br2

(33)

(14)

5[19[0[0[3 Carbonimidic diiodides\ I1C1NR

Isolable examples of this class of compounds are virtually unknown[ The likely reason is theirtendency to dissociate to iodine and the isocyanide[ For example\ N!alkylcarbonimidic dichloridesreact with potassium iodide with the liberation of iodine ð48JGU1020Ł^ the probable explanation isthat carbonimidic diiodides are formed as intermediates but then dissociate "Scheme 02#[

NR

I

IKI

NR

Cl

Cl

I2 + RNC

Scheme 13

Diiodoformaldoxime "23# has been isolated in good yield from the reaction of mercury or sodiumfulminate with iodine ð20LA"378#6\ 21CB54Ł[ The iminium salt I1C1NMe1

¦I− has been prepared"79)# by the reaction of the corresponding dichloroiminium chloride with iodomethane ð68ZOR104\70ZOR079Ł[

N

I

I

OH(34)

5[19[0[1 Iminocarbonyl Halides with Two Dissimilar Halogen Functions

There are relatively few examples of carbonimidic dihalides with di}erent halogens attached tocarbon[ Most contain ~uorine\ with chlorine present as the second halogen[

5[19[0[1[0 Carbonimidic chloride ~uorides\ ClFC1NR

ClFC1NH has been suggested as an intermediate in the reaction of HF with cyanogen chloride\but it has not been detected directly ð58HCA701Ł[ Several methods of preparation of ClFC1NF


have been described and the "E#! and "Z#!isomers have been identi_ed ð69JA2554Ł[ The methods ofpreparation are summarised in Scheme 03 ð56JGU0232\ 58JGU0290\ 69JA2554\ 62JOC0964Ł[

NF

F2N

F2NH2NCONHNH2•HCl

NF

F

Cl

NF2

F

Cl

Cl

Scheme 14

i or ii

i, Hg, 100 °C, 52%(E), 39%(Z); ii, Fe(CO)5, 10 °C, 43%

ClFC1NCF2 has been produced by the high temperature pyrolysis of 1\2!dichloroper~uoro!N!methylazetine and of copolymers of tri~uoronitrosomethane with chloro~uoroalkenes such astri~uorochloroethylene ð54JCS5198\ 61GEP1090096Ł[ This compound is also one of the productsobtained from the reaction of tri~uoromethyl isocyanide with chlorine ~uoride ð74IC3554Ł[ Reductiveroutes to the azine "24# ð60ZOR1156Ł and to the oxime "25# ð59JGU3918Ł have been described andthese are outlined in Scheme 04[

N

F

Cl

N

Cl

F

ClHI ON

Cl

F N

F

Cl

OH

H2SF N

N F

ClF

ClF

Scheme 15

(35) (36)

Chloro~uoroformaldoxime "25# is not isolable^ it is converted into a crystalline polymer when thesolution is concentrated[ However\ several series of phosphorus!substituted oximes have beenisolated and characterised from the reaction of dichloro~uoronitrosomethane with phosphites andother phosphorus"III# reagents[ Two examples\ one resulting from oxidative addition to a cyclicphosphorus"III# reagent without ring opening ð61JGU182Ł and the other resulting from ring openingð58JGU0124Ł\ are shown in Scheme 05^ many related reactions have been described ð58JGU0581\69JGU439\ 61JGU688\ 61JGU792\ 77KFZ032\ 78ZOB0344Ł[

N

F

Cl

O P N

O

NP

OOMe

MeMeO

CFCl2NO

96%

SP

ONEt2

N

F

Cl

O P

O

NEt2

SCFCl2NO

83%

Cl

Scheme 16

5[19[0[1[1 Carbonimidic bromide ~uorides\ BrFC1NR

A few of these compounds have been described[ Photolysis of a mixture of N1F3 and ~uoro!tribromomethane gave BrFC1NF as a mixture of "E#! and "Z#!isomers ð55IC0684Ł[ Reaction oftetrabromoformaldazine "21# with silver ~uoride gave a mixture containing BrFC1NN1CF1 "themajor component#\ BrFC1NN1CBrF and BrFC1NN1CBr1 ð55JOC2722Ł[

5[19[0[1[2 Carbonimidic bromide chlorides and carbonimidic chloride iodides\ ClXC1NR "X�Bror I#

There are a few salts which contain these functional groups[ The salts ClXC1NH1¦SbCl5−

"X�Br and I# have been isolated from the reaction of cyanogen bromide and cyanogen iodide withantimony"V# chloride and HCl ð53CB0175Ł and the crystal structure of the salt formed from cyanogenbromide has been determined ð82ZN"B#08Ł[ There are also examples of salts of the type "14^ R0�Br#ð77S544Ł[


5[19[0[2 Iminocarbonyl Halides with One Halogen and One Other Heteroatom Function

Compounds having this general structure are known with ~uorine\ chlorine\ bromine and iodineas the heteroatom[ The second heteroatom is most commonly oxygen\ sulfur or nitrogen[ Themethods of preparation of the oxygen\ sulfur and nitrogen compounds have been reviewed byUlrich ðB!57MI 519!90Ł and by Ku�hle ð58AG"E#19\ 72HOU"E3#432Ł[ Similar displacement reactions ofdihaloiminium ions are reviewed by Janousek and Viehe ðB!65MI 519!90Ł and by Marholdð72HOU"E3#544Ł[

5[19[0[2[0 Iminocarbonyl ~uorides with one other heteroatom function

"i# Iminocarbonyl ~uorides with an oxy`en function\ F"R0O#C1NR1

The parent compound of this type "R0�R1�H# is named in Chemical Abstracts as car!bono~uoridoimidic acid[ A few of these compounds have been prepared by the selective displacementof ~uoride from carbonimidic di~uorides by oxygen nucleophiles[ The reaction can be carried outon N!per~uoroalkylcarbonimidic di~uorides with alkoxides "Scheme 06# ð65IZV1270\ 81JFC"46#182Ł[Nitric acid has also been used as the nucleophile^ dropwise addition of concentrated nitric acid at−67>C gave the nitrate "26# ð57JGU26Ł[ An example of a related method in which the oxygennucleophile is generated in situ is shown in Scheme 07 ð71POL018Ł[ Two speci_c methods based ondi}erent approaches are also shown[ Thermolysis of the diazirine "27# at 79>C gave the carbenedimer as the major product\ but the azine "28# as a minor product "02)# "Equation "04## ð75TL308Ł[Compounds of this class have also been formed by thermal rearrangement of per~uorinated oxazi!ridines^ a C!per~uoroalkyl substituent of the oxaziridine migrates to oxygen in the rearrangementð82JCS"P0#494Ł[ A reductive dechlorination method provided a route to compound "39# "as a mixtureof the two isomers# in 68) yield "Equation "05## ð76AG"E#023Ł[

NCF3

F

RO

NCF3

F

F

NCF3

F

O2NO

(37)

NaOR HNO3, –78 °C

60%

Scheme 17

O

F3C F

NF

F

F3CF2COCsF

55%

F3C F

O–

FNF

F

F

Scheme 18

N

F N

MeO

OMe

F

(39)

N

NMeO

F

80 °C

(38)

(15)

NCl

F

F5SOZn, 50 °C

F5SOCFClNCl2

(40)

(16)

"ii# Iminocarbonyl ~uorides with a sulfur function\ F"R0S#C1NR1

Such compounds can be prepared in a manner analogous to those with an oxygen function\ bydisplacement of one ~uoride of carbonimidic di~uorides using a thiol as the nucleophile ð58JGU072Ł[


"iii# Iminocarbonyl ~uorides with a nitro`en function\ F"R0R1N#C1NR2

These compounds are described in Chemical Abstracts as carbamimidic ~uorides[ The additionof ammonia ð72IZV583Ł or primary alkylamines ð79JFC"04#058Ł to F1C1NCF2 leads to compoundsof this type having the general structure "30# in good yield[ With an excess of the carbonimidicdi~uoride 1 ] 0 adducts "31# can be isolated ð72MI 519!91Ł[ Trimethylsilyl azide reacts with F1C1NCF2

to give the a!azidoimide F"N2#C1NCF2 which shows no tendency to cyclise to the correspondingtetrazole ð74IZV699Ł[ The carbonimidic di~uoride F1C1NCF2 also reacts with antimony"V# ~uoride\either to give a cyclic trimer ð72JFC"11#064Ł or\ in liquid sulfur dioxide\ to give the salt"CF2#1NC"F#1N¦

1CFN"CF2#1SbF5− ð73JFC"15#210Ł[

NCF3

F

RHN

(41)

NCF3

F

NR

F

NCF3

(42)

The most numerous examples of compounds of this class are formal dimers "32# of carbonimidicdi~uorides[ In the presence of ~uoride ions the carbonimidic di~uorides can dimerise by the routeshown in Scheme 08[ This is in e}ect a special case of nucleophilic displacement of ~uoride[ Someexamples of dimers formed in this manner are listed in Table 2[ Related reactions are the combinationof F1C1NF with F1C1NBr to form a {mixed dimer| "33# ð77JOC3332Ł and with F3S1NF to give

Table 2 Dimers "32# of carbonimidic di~uoridesF1C1NR[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐF 71POL018\ 72JOC660\ 89JA617But 79TL3782CF2 76JFC"26#148\ 65IZV101Ph 55AG"E#737\ 79TL3782OCF2 70JFC"07#330TeF4 74IC3060N"CF2#C1F4 78IC2234*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

NR

F

NR

(43)

F

F

F

NR

F

F

FNR

F

F

F– –

Scheme 19

NRF

F

NBr

F

F3CN

F

(44)

NF

F

F5SN

F

(45)

the 0 ] 0 adduct "34# ð73IC1077Ł[Some useful speci_c preparations of compounds of this class have been described[ The N!

bromoimide "35# has been prepared in 89) yield from "CF2#1NCN\ bromine and caesium ~uorideð89JA617Ł and compound "36# in 73) yield from ~uorocyclohexane\ cyanogen chloride and hydro!


gen ~uoride ð58HCA701Ł[ The reaction of TeF4NHCF2 with potassium ~uoride gives the imide "37#"38)# ð74IC3060Ł[ The azoimide "38^ R�CF1NF1# has been obtained in low yield by thermolysisof per~uoroaminodiazirine ð56JHC278Ł and the related compound "38^ R�C"F#1NF# by reactionof the azo compound "49# with carbon monoxide at 079>C ð61IC307Ł[ The per~uoro compoundF1NCF1NF is produced in low yield by ~uorination of guanylurea ð56JOC2748Ł[ A potentiallymore general method of synthesis of this class of compounds which has not been exploited is theexchange of the chlorine of the corresponding imidoyl chlorides for ~uorine by the action ofhydro~uoric acid ð58AG"E#19Ł[

NBr

F

(CF3)2N

(46)

NCF3

F

HN

(47)

NCF3

F

F5TeHN

(48)

NF

F

N

(49)

N

R

NF2

F

NN

NF2

F2N

FF2N

(50)

"iii# Iminocarbonyl ~uorides with a phosphorus function

The reaction of triethyl phosphite or trimethyl phosphite with F1C1NCF2 leads to the formationof the adducts "RO#2P"F#C"F#1NCF2 in good yield ð66IZV1268\ 70IZV1521Ł[

5[19[0[2[1 Iminocarbonyl chlorides with one other heteroatom function

"i# Iminocarbonyl chlorides with an oxy`en function\ Cl"R0O#C1NR1

There are two principal methods for the preparation of compounds of this type "named inChemical Abstracts as derivatives of carbonochloridoimidic acid#[ The _rst\ and older\ method isthe selective displacement of one chloride from a carbonimidic dichloride by an oxygen nucleophile\usually an alkoxide or a phenoxide ion[ Several examples of reactions of this type are described byKu�hle ð58AG"E#19\ 72HOU"E3#432Ł[ The method recommended for reaction of alkoxides with N!arylcarbonimidic dichlorides is to use a two!phase system of chlorobenzene and aqueous alkali^ thisprevents further displacement of chloride[ Examples of this method of preparation include thosefor R1�alkyl ð71TL2428Ł\ aryl ð64CB1189\ 71TL2428\ 73ZOR0086Ł and SF4 ð71JFC"08#300Ł[

Reaction with phenoxides has been performed with equimolar quantities of reagents in a polarsolvent such as dioxane ð58AG"E#19Ł[ An example is the selective displacement of chloride from thedichloride "40# with phenol in the presence of triethylamine "Equation "06## ð64JCS"P1#0935\ 66ZC061Ł[

Cl

O

N

Cl

Cl Cl

O

N

PhO

Cl

PhOH, NEt3(17)

(51)

The second general method of preparation of these compounds is the reaction of aryl cyanateswith acyl chlorides "Equation "07## and with other active chlorine compounds such as sulfenylchlorides[ Several examples of this reaction are described in a review by Grigat ð61AG"E#838Ł[ Therange of examples has subsequently been extended[ With phosphorus pentachloride at −49>C thesalts "41# were formed in high yield ð61JGU86Ł[ The pyrone derivatives "42# have been isolated inlow yield from the reactions of aryl cyanates with malonyl chloride "which behaves as the pyroneacid chloride# ð74CB0260Ł and the {mixed| imidoyl chlorides "43# were isolated in moderate yield


from the reaction of Cl1C1NCOCl with aryl cyanates ð70ZOR287Ł[ Cyanates also react withchloroiminium salts to give salts of the type "14# ð77S544Ł[

(18)

O

N

Cl R

ArO

ArOCNRCOCl

N PCl PCl6–

Cl

ArO

3

(52)

+

O

N

Cl

ArO

O

O

Cl

HO

(53)

O

N

Cl N

ArO

Cl

Cl(54)

In principle the reaction of carbamate esters R0NHCO1R1 with phosphorus pentachloride couldprovide a third general method of synthesis\ but such reactions normally go further and yieldisocyanates[ In the reaction of F4SNHCO1Ph with phosphorus pentachloride some of the imidoylhalide F4SN1C"Cl#OPh was isolated as well as the isocyanate ð72JFC"12#482Ł[

"ii# Iminocarbonyl chlorides with a sulfur function\ Cl"R0S#C1NR1

These compounds have also been called 0!halothioformimidates[ The parent compound"R0�R1�H# is named as carbonochloridimidothioic acid in Chemical Abstracts[ The four principalmethods of preparation are exempli_ed below[

"a# From carbonimidic dichlorides[ The displacement of chloride from carbonimidic dichloridesby sulfur nucleophiles has been used as a method of preparation for a few types of compounds ofthis type\ including N!aryl\ aroyl and phosphoryl derivatives ð58AG"E#19\ 64CB1189\ 64JCS"P1#0935\73JOC417Ł[ For example\ the imidoyl chloride "44# was isolated "59)# from the reaction of thecorresponding carbonimidic dichloride with phenylmethanethiol and triethylamine ð73JOC417Ł[ Arelated reaction is the preparation of the heterocycle "45# from the imidoyl chloride "46# and sulfur"Equation "08## ð65GEP1340524Ł[

NCOPh

Cl

PhCH2S

(55)

S

NN

SCl Cl

Cl Cl

N NCl

Cl

Cl

Cl

S8

(57) (56)

(19)

"b# From isocyanides[ The addition of sulfenyl chlorides to isocyanides provides a general routeto compounds of this class ð51AG"E#536\ 73T0964\ 74JOC660Ł[ With bis"trimethylsilyl#amino isocyanide arange of sulfenyl chlorides has been used "Scheme 19# ð66ZN"B#0992Ł[ The addition of methanesulfenylchloride to isocyanides XCH1NC "X�EtO1C or "EtO#1PO# gives the compoundsMeSC"Cl#1NCH1X which are useful precursors to nitrile ylides ð81TL5044Ł[

"c# From isothiocyanates and related compounds[ As shown in Scheme 4 the preparation ofcarbonimidic dichlorides by chlorination of isothiocyanates goes by way of sulfenyl chloride inter!mediates and some of these intermediates are isolable ðB!60MI 519!90Ł[ For example\ the sulfenylchlorides "47# have been isolated in good yield from the reaction of the isothiocyanates with chlorineð67CB587Ł[ Chlorination of aryl isothiocyanates in the presence of thiols RSH leads to the formationof the compounds "48# ð89JHC0080Ł[ A related high yielding preparative method is the reaction ofcompounds "59^ X�COAr or SO1Ar# with sulfuryl chloride to give the chlorides "50# ð64AP"297#268\73CZ393\ 80JPR076Ł[ Thio! and dithiocarbamic esters PhNHCXSR "X�O or S# have also been


NN(TMS)2

Cl

Cl3CS

NN(TMS)2

Cl

Me2NS

S

(TMS)2NN

Cl

Cl

NN(TMS)2(TMS)2NN

Cl

S )2

Me2NSCl

68%

S2Cl2

96%

Cl3CSCl

93%

SCl2

93%

(TMS)2NNC

Scheme 20

chlorinated in high yield by means of the Appel reagent "triphenylphosphine and tetra!chloromethane# to give compounds of this type ð65CB709Ł[

NCOAr

Cl

ClS

(58)

NAr

Cl

RS

(59)

NX

RS

RS

(60)

NX

Cl

RS

(61)

"d# From thiocyanates[ The reaction of cyanates with acyl chlorides described by Grigatð61AG"E#838Ł has an analogy in the reaction of methyl or ethyl thiocyanate with oxalyl chlorideð67LA0693Ł[ With 1 mol of methyl thiocyanate and in the presence of boron tri~uoride the imidoylchloride "51# was formed "55)#[ The N!chloro compounds "52# have been isolated from the reactionof thiocyanates with iodine monochloride ð71MI 519!91Ł[ By analogy with the reaction shown inEquation "4# the three!component reaction of alkyl thiocyanates with chlorine and alkenes gavethe adducts "53# in moderate yield ð58JPR04Ł[ Ethyl thiocyanate is also reported to react withhydrogen chloride to give the 1 ] 1 adduct "54# "39)# ð62BCJ292Ł[ Salts of the type "14# are formedfrom thiocyanates and imidoyl chlorides ð77S544\ 81T7160Ł[ The methods of preparation of saltsR0SC"Cl#1NR1

1¦X− have been reviewed by Kantlehner ð68MI 519!91Ł[

N

Cl

MeS

N

SMe

O

O

Cl

(62)

NCl

Cl

RS

(63)

N

Cl

R1S

ClR2

(64)

N

Cl

EtS

NH2 Cl–

EtS

(65)

+

"iii# Iminocarbonyl chlorides with a selenium function\ Cl"R0Se#C1NR1

An example of a compound with this functional group is the selenazinone "56#\ which was formedby cyclisation of the selenocyanate "55# with HCl ð57AG"E#353Ł[

(66)

SeCN

Cl

O

(67)

Se

N

O

Cl


"iv# Iminocarbonyl chlorides with a nitro`en function\ Cl"R0R1N#C1NR2

The current Chemical Abstracts name for the parent compound "R0�R1�R2�H# is car!bamimidic chloride[ This compound is still unknown but its salts and many substituted carbamimidicchlorides have been described[ There are _ve principal methods of preparation[

"a# From carbonimidic dichlorides and dichloroiminium salts[ In principle the reaction of car!bonimidic dichlorides with amines provides a general route to carbamimidic chlorides\ but thereaction must be carried out under carefully controlled conditions in order to be a useful syntheticmethod[ For example\ displacement of chloride from N!aroylcarbonimidic dichlorides takes placein high yield with dialkyltrimethylsilylamines at low temperature "Equation "19## ð78LA820Ł[ Thereare several other useful examples of displacement of chloride from carbonimidic dichlorides bysecondary amines ð79CC768\ 72KGS687\ 77AG"E#0233\ 77JFC"39#106\ 78CB0896Ł one of which was shownto lead speci_cally to the "Z#!isomer ð82JPO208Ł[ Primary amines tend to react further to giveguanidines[ N!Phenylcarbonimidic dichloride reacts with cyclic tertiary amines to give quaternaryammonium salts "Scheme 10# which either demethylate "n�4 and 5# or undergo ring opening"n�1Ð3# above room temperature ð63TL2654Ł[ Triazinones "57# have been prepared by the reactionof the carbonimidic dichloride "7# with arylamines ð71CB2476Ł[

PhN

N

Cl

(CH2)n

PhN

N

Cl

(CH2)n

Me

PhHN

N(CH2)nCl

O

Me

Scheme 21

+ Cl–

NCOAr

Cl

Cl

NCOAr

Cl

R2NR2N-TMS, –45 °C

(20)

N

N

N

O

Ar

Cl Cl

(68)

The major route to N\N!dimethylcarbamimidic chlorides "58# is provided by the displacement ofchloride from the iminium salt "69# by amines\ dichloroamines and other nitrogen nucleophiles"Scheme 11# ðB!65MI 519!90Ł[ This reaction provides a wide range of compounds having the generalstructure "58#[ Many of these compounds are described in the review by Janousek and VieheðB!65MI 519!90Ł^ representative examples of reactions of the salt "69# with reagents of the generaltype RNH1 from this review and from later references are given in Table 3[

NMe2 Cl–

Cl

Cl

NMe2 Cl–

Cl

RHN

NMe2

Cl

RN+ +RNH2 –HCl

(70) (69)

Scheme 22

N\N!Dichlorourethanes ð64ZOR60Ł and N\N!dichlorosulfonamides ð62ZOR32\ 67ZOR0730Ł alsoboth react with the iminium salt "69# to give compounds of general structure "58#\ with the elim!ination of chlorine[ A variety of other nitrogen compounds react with the salt "69#] some examplesare shown in Scheme 12 ð63ZOR25\ 64C198\ 67BSB280\ 68AG"E#222\ 73ZOB0009\ 75T5534Ł[

"b# From thioureas[ Several types of thiourea can be converted in good yield into carbamimidicchlorides by reaction with an equimolar amount of phosgene ðB!57MI 519!90Ł[ An example is thepreparation of the N!p!toluenesulfonylimide "60# "77)# from the thiourea[ A variant of this methodis provided by the reaction of N!acetylthiourea with phosphorus pentachloride\ which gave theimide "61# "60)# ð89ZOB695Ł[ N!Sulfonylcarbamimidic chlorides have also been obtained by chlori!nation of S!methylisothioureas ð64ZOR1132\ 79CP0965021Ł[


Table 3 Carbamimidic dichlorides "58# from the iminium salt "69#and RNH1[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐYield

R ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐC5H3NO1!3 79 60AG"E#462C5H3CN!1 quant[ 73TL0446CO1Et 61 B!65MI 519!90CH1C"CN#1 71UKZ284OCH1Ph 80 B!65MI 519!90SO1Ph 57 71LA1094N"Me#C5H2"NO1#1!1\3 77 79JCS"P1#756*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

Me2N NCN

CNCN

ClClMe2N

N3 Cl–

Cl

N

Cl

Me2N

Cl3C

Cl

CN

Me2N

N

Cl

• O

Me2N NF

Cl Cl

MeN

Cl

Me2N

Cl

Cl

Cl

NMe2 Cl–

N

N

N

O-TMS

O-TMSTMS-O

Cl

Cl

Cl

NCO

NCCHC(CN)2 K+

NC

+

NCN

CCl3

(70)

+

+

TMS

+

F CONHMe

SbCl5

Scheme 23

TMS-N3

62%

70%

70%

86%

–

Cl–

Cl

Cl

SbCl6–

(71)Cl

BuHN

NTs

(72)

Cl

N

Cl NPOCl2

Cl

H

"c# From ureas[ Ureas can also be chlorinated with phosgene\ but attack on oxygen\ rather thanon nitrogen\ which is the favoured reaction only with ureas having secondary or tertiary alkylsubstituents on nitrogen ðB!57MI 519!90Ł[ An example of the reaction is shown in Equation "10#ð75JOC0608Ł[ There are also several examples of chlorinations of this type which have been carriedout with the triphenylphosphineÐtetrachloromethane reagent ð62CB1982\ 63CB587\ 65CB0532\ 65CB1810\68CB539\ 79CB0984Ł and with phosphorus"V# chloride ð80ZOB532\ 81ZOB295\ 81ZOB213Ł[

Cl

Me2N

NPri

O

Me2N

NHPriCOCl2, 0 °C

99%(21)

"d# From cyanamides[ Dialkylcyanamides add to electron de_cient aroyl chlorides to give car!bamimidic chlorides\ generally in good yield[ The reaction was _rst described by Bredereck andRichter ð55CB1343Ł but was later greatly expanded\ especially by Ried et al[ ð79S508Ł[ The method


is exempli_ed by the preparation of the imidoyl chloride "62# "85)# from 3!nitrobenzoyl chlorideand N!cyanopyrrolidine "Equation "11##[ The reaction has been performed with a variety of aroylchlorides ð79CB1472\ 79S508Ł and other activated acyl chlorides ð79S508\ 70MI 519!91\ 75LA0886Ł[ Otheractivated halogen compounds also react with dialkylcyanamides to give carbamimidic chlorides]examples of reaction with sulfenyl chlorides ð79S508\ 76CZ228Ł\ sul_nyl chlorides ð79S508Ł\ di!arylimidoyl chlorides ð76CC88Ł\ chloroiminium salts ð73CC0094\ 77S544\ 78S807\ 81T7160\ 81JHC0440\82H"25#0410Ł\ thionyl chloride ð63ZOR0999Ł\ sulfur dichloride ð74IC1342Ł\ sulfuryl chloride ð62ZOR522Łand phosphorus trichloride ð67JGU0967Ł are known[ Some of these are illustrated in Scheme 13ð78S807Ł[

N N +

O

N

Cl

N

NO2

COClO2N (22)

(73)

R2N N

N

Cl

Me2N

N

Ar

Ar

NMe2

NAr

Ph

N

Cl

R2N

SAr

N

Cl

R2N

NMe2 Cl–

Cl

N

Cl

R2N

OS

Ar

N

Cl

R2N

PCl2

N

Cl

R2N

OS

Cl

N

Cl

R2N

Scheme 24

+

+

NMe2 Cl–

Cl

Ar2CCl+ SbCl6–

R = Me

ArN

Cl

Ph

ArSOCl

SOCl2 PCl3

ArSCl

+

SbCl6–

Cyanamide itself has long been known to add to dry hydrogen chloride to give iminium salt "63#ðB!57MI 519!90Ł[ The salt is a solid which can be stored for short periods in anhydrous conditionsð89JMC323Ł[ Cyanamide is also chlorinated by hypochlorous acid to give the perchloro compound"64# ð70MI 519!92Ł[ The N!chloroimide has been prepared by the reaction of thionyl chloride withsalts of dicyanamide ð69JCS"C#764Ł and several other carbamidic chlorides have been derived fromit by reaction with nucleophiles[

NH2 Cl–

Cl

H2N+

(74)

NCl

Cl

Cl2N

(75)

"e# From carbodiimides[ Diisopropylcarbodiimide and other carbodiimides with secondary alkylsubstituents have been shown to react with activated halogen compounds to give carbamimidic


chlorides[ The reaction has been described with phosgene and thiophosgene by UlrichðB!57MI 519!90Ł[The reaction with trichlorotriazine is shown in Equation "12# ð71KGS010Ł^ the same type ofreaction takes place with benzoyl chloride ð74AP"207#0946Ł\ aliphatic acid chlorides includingchloroacetyl chloride ð55CB2044\ 66JOC2119Ł\ squaric acid dichloride ð74AP"207#881Ł and hydrogenchloride ð78TL1268Ł[ The reaction with phosphorus pentachloride leads to the formation of six!coordinate phosphorus species "65# with partial CN double bonds and with two equivalent phos!phorusÐnitrogen bonds ð57AG"E#188\ 58AG"E#344\ 89IC4970Ł[

N

N

N

Cl Cl

PriN NPri

N

N

N

Cl Cl

Cl

•PriN NPri +85%

(23)

Cl

ClN

PN

Cl

Cl

Cl

Cl

R

R

(76)

"v# Iminocarbonyl chlorides with a phosphorus function

There are a few compounds containing this functional group[ The phosphonates "66# are formedin good yield by the reaction of the isocyanate Cl1P"O#CCl1NCO with alcohols ð60ZOB1044Ł[ Thechlorooxime "67# is the major product of the nitrosation of compound "68# ð89ZOB112Ł^ it is aprecursor to the phosphorus substituted nitrile oxide "79# ð82ZOB526Ł[

P

N

CO2RCl

(77)

O

RO

RO

P

N

OHCl

(78)

O

PriO

PriO

P

Cl

(79)

O

PriO

PriO

OH

(80)

N+ O–P

O

PriO

PriO

"vi# Iminocarbonyl chlorides with a metalloid or a metal function

The insertion of alkyl isocyanides into boronÐhalogen bonds of BX2 or into metalÐchlorine bondshas provided a route to compounds of this type[ The reactions are summarised in Scheme 14ð58M0712\ 64JOM"090#C0\ 66JCS"D#1904\ 68JOM"070#58Ł[ The unstable adducts formed with titanium"IV#chloride are useful synthetic intermediates ð77CB496Ł[

X3BNR

BX3

RNX

X

+

+

–

–

R N C[MCl4{C(Cl)=NR}CNR] [MCl3{C(Cl)=NR}CNR]2

MCl4

BX3

MCl5

M = Ta, Nb; R = Me, But M = Ti, Hf, Zr; R = But

Scheme 25


5[19[0[2[2 Iminocarbonyl bromides and iodides with one other heteroatom function

Several examples of compounds of this type have been described with either sulfur or nitrogen asthe second heteroatom attached to carbon[ The synthetic methods are analogous to some of thoseused for the corresponding iminocarbonyl chlorides[

Alkyl thiocyanates RSCN have been found to react with bromine and with iodine to give 0 ] 0adducts having the structure "70^ X�Br or I# ð71MI 519!90\ 71MI 519!91Ł[ The addition of SF4Br totri~uoromethyl isocyanide gave the imidoyl bromide "71# "51)# ð74IC3554Ł[ Compounds of thistype which have been prepared by nucleophilic displacement are the hydrazones "72#\ which arederived from the corresponding dibromo compounds by reaction with thiophenolate anionsð61JCS"P1#0949Ł and the iminium salt "73#\ which is formed from the chloroiminium salt by reactionwith iodomethane ð70ZOR079Ł[

RS

NX

X(81)

F5S

NCF3

Br(82)

Ar1S

NNHAr2

Br(83)

Me2N

NMe2 I–

I(84)

+

Addition reactions of cyanamides have also been used to prepare carbamimidic bromides andiodides[ Cyanamide reacted with hydrogen bromide and hydrogen iodide to give the salts "74# ingood yield ð69GEP0804557Ł and the addition of hydrogen bromide to diethylcyanamide or to N!cyanopyrrolidine also gave the corresponding bromoiminium salts ð77JCS"P0#788Ł[ Similarly theiminium salts "75^ X�Br and I# were formed from the sodium salt of the corresponding cyanamideby addition of hydrogen bromide or hydrogen iodide ð65CPB15Ł[ The squaric acid derivatives "76^X�Br and I# have been prepared by addition of the corresponding halides to N!cyanopyrrolidineð79S508Ł[

H2N

NH2 X–

X(85) X = Br or I

+NCCH2CONH

NH2 X–

X(86)

+

Ph

OO

NN

X

(87)

Examples of imidoyl halides with a phosphorus function are provided by the hydrazone "77#"which is prepared by a method analogous to that used for the oxime "67## ð78ZOB603Ł and by thediazo compounds "78^ X�Br and I\ R�Ph and OMe# which are prepared by halogenation of thecorresponding "78^ X�H# ð68LA0991Ł[

P

NNHAr

Br(88)

O

PriO

PriOP

N2

X(89)

O

R

R

5[19[1 FUNCTIONS CONTAINING AT LEAST ONE CHALCOGEN "AND NO HALOGENS#

5[19[1[0 Iminocarbonyl Compounds with Two Similar Chalcogen Functions

5[19[1[0[0 Iminocarbonyl compounds with two oxygen functions

The parent compound of this class\ "HO#1C1NH\ is named in Chemical Abstracts as carbonimidicacid[ Derivatives are also called iminocarbonates[ The most extensive review of the methods ofpreparation of these compounds is by Ku�hle ð72HOU"E3#450Ł[


"i# From carbonimidic halides and related compounds

The reaction of carbonimidic dichlorides with sodium alcoholates or phenolates in a 0 ] 1 molarratio\ and sometimes with alcohols in excess\ provides a general route to carbonimidic diesters "89#"Equation "13## ð58AG"E#19Ł[ Examples include the formation of the diethoxyiminium salt "80# fromthe corresponding dichloroiminium salt and ethanol ð55ZAAC"233#002Ł\ the diester "81# from thecarbonimidic dichloride and sodium methoxide ð70JHC0016Ł\ dimethyl N!cyclohexyliminocarbonatefrom the carbonimidic dichloride and sodium methoxide ð76CB228Ł and the polymer "82# from N!phenylcarbonimidic dichloride and bisphenol A ð80MM1291Ł[ N!Arylcarbonimidic dichlorides havealso been used to trap the intermediates formed in the electrochemical reduction of diaryl!0\1!diketones\ giving the cyclic iminocarbonates "83# ð83TL1254Ł[

NR1

Cl

Cl

NR1

R2O

R2O2 R2O–Na+

(90)

(24)

EtO

NH2+ SbCl6–

EtO(91)

MeO

NCH2Ts

MeO(92) (93)

O

O

PhN

n

(94)

O

O

Ar2

Ar2

NAr1

Carbonimidic diesters have also been prepared by displacement of ~uoride from the correspondingcarbonimidic di~uorides ð89JFC"37#284\ 81JFC"46#182Ł[ For example\ compound "84# was isolated"69)# from the reaction of the corresponding di~uoride with lithium 1\1\1!tri~uoroethoxideð89JFC"37#284Ł[ Instead of halide\ 0\1\3!triazolide can also act as a leaving group for the preparationof carbonimidic diesters ð62JPR539Ł[

CF3CH2O

N

CF3CH2O(95)

N(CF3)2

"ii# From cyano`en halides\ cyanates and isothiocyanates

N!Unsubstituted carbonimidic esters have been prepared by nucleophilic addition of alcohols tocyanogen chloride\ to cyanogen bromide or to cyanate esters ð72HOU"E3#450Ł[ The addition tocyanate esters allows esters to be prepared which have two di}erent oxygen substituents "Equation"14##[ An example is the preparation of the methyl 3!tolyl ester "R0�Me\ R1�3!MeC5H3#"84)# from 3!tolyl cyanate and methanol ð62JPR178Ł[ A useful method for the preparation of"PhO#1C1NH is the reaction of potassium cyanide with two equivs[ of phenyl cyanate] cyanidedisplaces phenoxide from one mole of phenyl cyanate and this then adds to the second mole togive the iminocarbonate in high yield ð54CB2551Ł[ Iminocarbonates can also be obtained fromisothiocyanates\ an example being the preparation of 1!"N!phenylimino#!0\2!dioxolane "82)# fromphenyl isothiocyanate and Bu1Sn"OCH1CH1O# ð66BCJ2160Ł[

NH

R2O

R1OR1OH

(25)NR2O

"iii# From dichlorobis"aryloxy#methanes and orthocarbonates

Dichlorodiphenoxymethane is a useful intermediate for the preparation of carbonimidic aciddiphenyl esters "Equation "15##[ It has been shown to react with cyanamide to give the N!cyano


compound "R�CN# "89)# ð71JHC0194Ł[ An analogous route has been used to prepare the amino!sulfonyl compound "R�SO1NH1# "56)# ð80S642Ł[

NR

PhO

PhO(26)

PhO

PhO

Cl

Cl RNH2

Reactions of primary amines with tetraethyl orthocarbonate and with trialkyl orthoformateshave also been used to prepare iminocarbonates ð69BCJ076\ 66MI 519!91Ł[ Triethyl orthocarbonatealso reacts with arenesulfonamides to give the N!arenesulfonyl iminocarbonates in good yieldð52JOC1891Ł[

"iv# By functional `roup interconversion on nitro`en

For several types of N!substituted carbonimidic diesters the most convenient method of prep!aration is from another carbonimidic diester "Equation "16##[ Examples of these reactions aresummarised in Table 4[ The simplest type is from N!unsubstituted compounds which are halo!genated\ alkylated or acylated\ but in other cases the imidoyl nitrogen of the product is derivedfrom the reagent[ Thus\ the conversion of dimethyl N!phenyl carbonimidate into the N!tosylcompound takes place by a ð1¦1Ł cycloadditionÐcycloreversion process ð76CB228Ł[

NR3

R1O

R1O(27)NR2

R1O

R1O

Table 4 Carbonimidic diesters prepared by exchange of N!substituents "Equation "16##[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

YieldR0 R1 R2 Rea`ent ")# Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐEt H Cl Cl1 47 25CB1247Et H CHPh1 Ph1CHNH2

¦Cl− 22 76CB0160Ph H CH1OMe ClCH1OMe 49 76CB0160Me H "CF1Cl#1COH "CF1Cl#1CO 72 51USP2004402Et H COMe MeCOCl 76 66ACH66Et H !COCO! "COCl#1 77 66ACH66Et H CO1Et ClCO1Et 57 75CB2125Et H CSNHPh PhNCS 11 64ZOR1112Et H PPh1 Ph1PCl ×79 60CB00881!NO1C5H3 H SO1NHMe ClSO1NHMe 71 74TL30381!NO1C5H3 H !SO! SOCl1 66 76S069Et H NHTs TsNHNH1 43 52PCS269Me H CN H1NCN 62 79EUP03953Et Cl OH NH1OH 79 02CB1336Et Cl 3!NO1C5H3SCl1 3!NO1C5H3SCl 72 74ZOR0170Me Ph Ts TsNCO 80 76CB228*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

"v# By O!alkylation of alkoxycarbonyl functions

Carbamate esters can be alkylated on oxygen with trialkyloxonium tetra~uoroborates\ andthis reaction provides a route to some carbonimidic diesters ð76CB228Ł[ Thus\ ethyl N!methyl!carbamate\ EtO1CNHMe\ gave diethyl N!methyliminocarbonate "42)# when alkylated with tri!ethyloxonium tetra~uoroborate[ Cationic species can also be produced by this method] someexamples are shown in Scheme 15 ð76CB0160\ 81CB1376Ł[ There are also examples of N!"tri!methylsilyl#carbamates which exist in equilibrium with O!trimethylsilyl isomers ð65IZV1436Ł[


NCO2Et

But

But

N

But

But OEt

OEtBF4

–+Et3O+BF4

–

72%

NCO2Et

MeO

MeO

Ph3P NCO2Et Ph3P N

OEt

OEtSbCl6–

+

N

MeO

MeO OEt

OEtBF4

–+Et3O+BF4

–

quant.

Et3O+SbCl6–

91%

Scheme 26

"vi# Other methods

Azodicarboxylic esters are useful partners in DielsÐAlder reactions[ They normally act as dieno!philes but they can sometimes act as heterodienes ð72CJC0102\ 78JA1884Ł^ for example\ 2\3!dihydro!1H!pyran and dibenzyl azodicarboxylate reacted to give the cycloadduct "85# "69)# ð78JA1884Ł[

(96)

O O

NN

CO2Bn

OBn

Hydrazine sulfate is reported to react with bis"trimethylsilyl#amine and carbon dioxide to givethe compound "86# as a separable component of a mixture with N!trimethylsilyl isomers ð77ZOB282\80ZOB0191Ł[

N

TMS-O

TMS-O

N

O-TMS

O-TMS

(97)

5[19[1[0[1 Iminocarbonyl compounds with two sulfur functions

The parent compound of this class\ "HS#1C1NH\ is named in Chemical Abstracts as car!bonimidodithioic acid[ The compounds are also often referred to as iminodithiocarbonates[ Methodsof preparation have previously been reviewed by Ku�hle ð72HOU"E3#468Ł[

Most of the methods of preparation of these compounds are analogous to those used foriminocarbonates^ however\ because of the relative ease with which sulfur can be alkylated\ alkylationmethods are more important than for the oxygen compounds[

"i# From carbonimidic halides

This method of preparation has not been used extensively[ Carbonimidic dichlorides react withthiols or thiolate anions with displacement of one "Section 5[19[0[2[1# or both chloride ions "Scheme16#[ The reaction is successful with carbonimidic dichlorides bearing a range of substituents onnitrogen ð72HOU"E3#468Ł[ Di}erent sulfur substituents can be introduced by successive displacement^for example\ compound "87^ R2�Ph# was prepared "57)# from the intermediate "88^ R0�Ts\R1�Me# and sodium thiophenolate ð75ZC193Ł[ Successive displacement of bromide by di}erentsulfur nucleophiles has also been carried out with a carbonimidic dibromide Br1C1NN1CHAr


ð61JCS"P1#0949Ł[ The carbonimidic di~uoride F1C1NCF2 reacts in an analogous way with thiolsð58JGU072Ł[

NR1

Cl

Cl

NR1

Cl

R2S

NR1

R3S

R2S

(99) (98)

Scheme 27

"ii# From cyano`en chloride and thiocyanates

Cyanogen chloride reacts with dithiols such as ethane!0\1!dithiol and benzene!0\1!dithiol in thepresence of HCl to give hydrochloride salts of N!unsubstituted iminodithiocarbonates^ an exampleis the salt "099# derived "53)# from propane!0\2!dithiol ð72HOU"E3#468Ł[ Alkyl thiocyanates alsoreact with thiols to give compounds of this type\ including those in which the sulfur substituents aredi}erent ð72HOU"E3#468Ł[

NH2+ Cl–

S

S

(100)

"iii# Methods involvin` S!alkylation

A variety of activated amino compounds can be converted into S\S!dialkyl iminodithiocarbonatesby reaction with a base\ carbon disul_de and a haloalkane "usually iodomethane# "Scheme 17#ð72HOU"E3#468Ł[ The method was used initially to convert sulfonamides into the dithioestersRSO1N1C"SMe#1 ð55CB1774\ 80S119Ł but it also works well with cyanamides ð66ZAAC"323#004\73CCC1174Ł\ with aromatic primary carboxamides ð68S443Ł and with heteroaromatic amines includ!ing 1!aminothiazoles ð80JCR"S#059Ł and 1!aminobenzothiazoles ð71S489Ł[ S!Alkylation and S!acyl!ation of the intermediates shown in Scheme 17 can also be used as a method of preparation[Dithiocarbamates R0NHCS1R1 can be alkylated in high yield to give iminodithiocarbonates bearingeither identical or di}erent substituents on sulfur ð71LA120\ 72HOU"E3#468\ 72S264\ 74S780Ł[ Dithio!carbamates R0

1NCS1R1 can also be alkylated on sulfur to give salts[ The salt "Me1S#1C1NMe1¦I−

has been prepared "79)# in this way^ it can also be made by N!alkylation of "Me1S#1C1NMeð55CB2157Ł[ The tosylhydrazones "090#\ which are useful as precursors to bis"alkylthio#carbenes\can similarly be made by alkylation of TsNHNHCS1Me ð61CC243\ 76S156Ł or of the potassium saltTsNHNHCS1

−K¦ ð55LA"583#33Ł[ Reaction of this salt with a!chloroketones results in the formationof the cyclic iminodithiocarbonates "091# in good yield ð78S021Ł[ An intramolecular S!alkylationoccurs when the dithiocarbamate "092# is treated with isocyanates^ the thiadiazoles "093# are formedin high yield ð73JOC0692Ł[ Similarly\ attempts to prepare compound "095# by S!methylation of thesalt "094^ X�NHCS1Me# resulted in its formation in poor yield\ the major product being 1\4!bis"methylthio#!0\2\3!thiadiazole resulting from intramolecular S!acylation ð75ZAAC"422#88Ł[

Scheme 28

XNH2 NHX–S

S

NHX

RS

SCS2, base RHal RHal

NX

RS

RS

NNHTs

RS

MeS

(101)

NNHTsS

S

R1

R2

(102)

NNHCS2Me

(103)


N

S N

MeS

CONHR

(104)

NX

(105)

K+ –S

K+ –SN

MeS

MeS N

SMe

SMe

(106)

The salt "094^ X�CN# can also be protonated by treatment with HCl in ether at −19>C^ however\protonation occurs predominantly on nitrogen to give a zwitterionic product ð66ZAAC"323#009Ł[


The NH group of iminodithiocarbonates can be substituted by a variety of electrophilesð72HOU"E3#468Ł\ including isocyanates\ acyl chlorides\ sulfamoyl chlorides ð74TL0094Ł and aromaticsulfenyl chlorides[ N!Hydroxyiminodithiocarbonates can be made using hydroxylamine[ The reac!tions are analogous to those of iminocarbonates shown in Equation "16# and Table 4[

"v# Other methods

Diazosulfones "R�Ph\ Ar or Et# have been prepared by diazo transfer "Equation "17## usingtosyl azide and a base ð53CB624\ 83T2084Ł[

N2

RO2S

RO2S

RO2S

RO2STsN3, base

(28)

5[19[1[0[2 Iminocarbonyl compounds with two selenium functions

A few compounds with this functional group are known ð60JPR793\ 61BCJ378\ 79CC755Ł[ Oneexample is the salt "096#\ which was prepared from Cl1C1NMe1

¦Cl− by successive reaction withhydrogen selenide and triethylamine\ then 2!bromobutan!1!one and tri~uoroacetic acid ð79CC755Ł[

NMe2+ –OCOCF3

Se

Se

(107)

5[19[1[1 Iminocarbonyl Compounds with Two Dissimilar Chalcogen Functions

5[19[1[1[0 Iminocarbonyl compounds with one oxygen and one sulfur function

The parent compound of this class\ HO"HS#C1NH\ is named as carbonimidothioic acid inChemical Abstracts[ Most of the methods for the preparation of derivatives are analogous to thoseused for compounds with two oxygen or two sulfur functions[


Carbonimidothioic esters "097# bearing a variety of substituents have been prepared by dis!placement of chloride from carbonimidic chlorides and appropriate oxygen or sulfur nucleophiles"Scheme 18# ð53JGU3038\ 72HOU"E3#450Ł[ Both chloride functions of N!benzenesulfonylcarbonimidicdichloride can be displaced by 1!thiolethanol and similar bidentate nucleophiles^ thus\ the oxathi!


olane "098# is prepared in good yield ð56AP"299#442Ł[ The reaction is probably a general one] it hasalso been reported for the N!phenyl! ð53JGU3038Ł and the N!benzoyl! ð55CB0801Ł carbonimidicdichlorides[

NR3

R2S

Cl

NR3

R2S

R1O

NR3

Cl

R1OR2S– R1O–

(108)

Scheme 29

NSO2PhO

S

(109)

"ii# From cyanates and thiocyanates

N!Unsubstituted compounds of this class are most easily prepared either by the addition of thiolsto cyanates or from alcohols and thiocyanates "Scheme 29# ð53CB2911\ 72HOU"E3#450Ł[ Cyanogenchloride can also be used as a starting material\ with 1!thiolethanol and related compounds\ for thepreparation of cyclic derivatives such as "009#[ An alternative method of preparation of the salt"009# is the reaction of HSCN with ethylene oxide and HCl ð47HCA266Ł[

Scheme 30

NH

R2S

R1OR2SH R1OH

NR1O NR2S

NH2+Cl–

O

S(110)

"iii# S!Alkylation methods

A simple method for the preparation of compounds of this class is\ in principle\ the S!alkylationof anions "000# derived from O!alkyl thiocarbamates ð62JCS"P0#1533Ł[ In practice the most e.cientway of bringing about the reaction is often to generate the anions in situ from isothiocyanates andalkoxide ions "Scheme 20# ð64ZOR0517\ 81TL0914Ł[ A variant of this reaction is the reaction of acylisothiocyanates with propargyl alcohol] the intermediates "001# undergo spontaneous cyclisation togive the cyclic iminothiocarbonates "002# ð62CPB51Ł[ An intramolecular alkylation also accountsfor the formation of the dihydrothiazole "003# "61)# from Br"CH1#1NCS and phenoxide anionsð73CCC184Ł[ Oxiranes ð67JOC2621Ł and nitrile oxides ð54T0426Ł can also add across the C1S bondof isothiocyanates[

Scheme 31

NR3

–S

R1OR1O– R2Hal

NR3•S NR3

R2S

R1O

(111)

The procedure illustrated in Scheme 17 for the preparation of iminodithiocarbonates has beenapplied to the preparation of compounds such as "004# by using the sodium salt of cyanamide and


NCOR

(112)

O

HS

NCORO

S

(113) (114)

N

S

PhO

COS in place of CS1 ð72ZAAC"490#046\ 72ZAAC"490#065Ł[ O!Acyl compounds can also be prepared bysuccessive S!alkylation and O!acylation of the intermediate formed from sodium cyanamide andCOS ð72ZAAC"490#058Ł[

NCN

(115)

MeO

MeS


Reactions of the type shown in Equation "16# and Table 4 are also possible with this class ofcompounds\ although fewer examples have been reported ð72HOU"E3#450Ł[ N!Acylation can becarried out using acyl chlorides and sulfonation by sulfonyl chlorides ð89GEP2730074Ł[ Hydroxyl!amine reacts with salts such as "009# to give the corresponding hydroxyimino derivatives\ andpotassium cyanate introduces the CONH1 group on to nitrogen ð47HCA266Ł[

"v# Other methods

The diester "005# has been prepared "69)# by heating phenyl isothiocyanate with dimethylformamide diethyl acetal\ Me1NCH"OEt#1 ð66CB26Ł[ A good route to compounds "097^ R2�CN#is the reaction of the dithioesters "006# with cyanamide and a base\ followed by S!alkylationð69AP"292#514\ 73JHC50Ł[ The salts "007# have been obtained from the iminodithiocarbonates "008#and potassium hydroxide ð76PS"18#0Ł[

NPh

(116)

EtO

EtSS

(117)

R1O

EtS

NCN

(118)

K+ –O

RS

NCN

(119)

RS

RS

5[19[1[1[1 Iminocarbonyl compounds with one oxygen or sulfur and one selenium or telluriumfunction

Several cyclic structures incorporate functional groups of these types[ The salts "019# have beenprepared by acid catalysed cyclisation of a!selenocyanoketones\ R0COCH1R1SeCN ð78EGP169429Ł[Analogous thiaselenoliminium salts\ such as "010#\ are formed when the thiaselenazines "011# aretreated with HI ð73S556Ł[ The imines "012^ X�NPh or NCO1Et# are conveniently prepared from thecorresponding thiones "X�S# by reaction with azidobenzene or with ethyl azidoformate ð79JHC006Ł[


Compound "012^ X�NPh# has also been prepared from phenyl isothiocyanate and the anionPhC2CSe− ð60JPR793Ł[ Reaction of the tellurium compound "013# with bromine gave a solidproduct which was formulated as "014# but it was too unstable to characterise fully ð70JOM"106#218Ł[

NH2+X–

O

Se

R1

R2

(120)

NH2+ I–

S

Se

Ph

(121)Se

N

SPh SEt

(122)

XS

Se

Ph

(123) (124)

Te NMe2

S NMe2+Br3

–S

Te

BrBr

Br

(125)

5[19[1[2 Iminocarbonyl Compounds with One Chalcogen and One Other Heteroatom Function

5[19[1[2[0 Iminocarbonyl compounds with one oxygen and one nitrogen function

These compounds\ commonly called isoureas and named in Chemical Abstracts as derivatives ofcarbamimidic acid\ H1N"HO#C1NH\ are widely represented in the literature[ The most com!prehensive survey of methods of preparation is by Ku�hle ð72HOU"E3#476Ł[ A review by Mathiasð68S450Ł on isoureas as alkylating agents also contains a survey of methods for their preparation[

"i# From carbonimidic halides\ esters and thioesters

One of the most general methods of preparation of isoureas "015# is the displacement of a leavinggroup on the imidoyl carbon of carbonimidic halides\ esters and thioesters by a nucleophile[ Thetypes of reaction which have been used are outlined in Scheme 21[

NR4

R2R3N

Hal

NR4

R2R3N

R1O

(126)

C R1O–

NR4

Hal

Hal

NR4

R1S

R1S

NR4

R1O

R1O

NR4

Hal

R1O

R2R3NH

B

A E

HOCH2CH2NH2*

D

R2R3NH

HOCH2CH2NH2*

* Methods D and E require this or a similar bidentate nucleophile

Scheme 32

Method A\ the displacement of halide from haloformamidic esters\ is a useful one when appro!priately substituted starting materials are available[ An example is the formation of "015^R0�R1�R2�Me\ R3�Ph# in high yield from methyl N!phenylchloroformamidate and di!methylamine ð72HOU"E3#476Ł[ The zwitterionic triazolones "016# are also formed by a reaction ofthis type from PhO"Cl#C1NCOCl and 0\0\disubstituted hydrazines ð73JOC1393Ł[ The displacementof an oxygen function by an amine "method B# has been used more widely[ Several iminocarbonates\especially those with an electron!withdrawing substituent R3 on nitrogen\ participate in this reaction


readily[ Some compounds of this type which react with primary and secondary amines are listed inTable 5[

Table 5 Carbonimidic diesters "R0O#1C1NR3 useful for preparation ofisoureas "method B in Scheme 21#[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐR0 R3 Ref[*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐEt Ts 52JOC1891Et CN 56CB1593Me CN 74OPP145\ 80OPP610Ph CN 76AF0997\ 76JHC164\ 77AF6\ 78JOC0951Ph COPh 76AF0992Ph SO1NH1 80S642Ph SO1C5H3Cl!1 77GEP"O#2523818*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

N–N

N

PhO

O

RR

(127)

+

Formamidinium chlorides bearing a variety of substituents on nitrogen react with alcoholates orphenolates to give isoureas "method C# ð72HOU"E3#476\ 75GEP"O#2493342Ł[ Fluoride can also bedisplaced\ as in the formation of the isourea "017# from the corresponding formamidinium ~uorideð73JFC"15#210Ł[ Methods D and E require the introduction of both nitrogen and oxygen functions^both are therefore essentially restricted to the formation of cyclic isoureas from 1!aminoethanoland related nucleophiles ð72HOU"E3#476\ 74BCJ2268Ł[

NCF2N(CF3)2

(128)

EtO

(F3C)2N

"ii# From cyano`en halides\ cyanates and cyanamides

The reaction of cyanate esters with amines leads to isoureas\ as shown in Scheme 22[ Stronglybasic aliphatic primary and secondary amines give 0 ] 0 adducts ð72HOU"E3#476Ł although in thepresence of an excess of the cyanate\ primary amines can give 1 ] 0 adducts ð53CB2916Ł[ Hydroxyl!amine adds to phenyl cyanate to give a 0 ] 0 adduct ð71JOC3066Ł[ Cyanogen chloride and cyanogenbromide can give isoureas with suitable bidentate nucleophiles such as 1!aminophenols[ A morewidely used method is the addition of alcohols to cyanamides[ This approach is illustrated by theformation of the isourea "018# "57)# from dimethylcyanamide and but!2!en!1!ol ð80S75Ł and of"029# "70)# from benzyl alcohol\ cyanamide and p!toluenesulfonic acid ð76TL0858\ 89TL3604Ł[ Arelated reaction is the conversion of the nitrilium salt "020# "Ad�0!adamantyl# into the isouroniumsalt "021# by reaction with methanol ð73CB491Ł[

NH

R22N

R1OR3NH2R2

2NHNR1O

NH

R3N

R1O

R1O

NH

Scheme 33


O

Me2N

NH

(129)

O

H2N

NH2+ –OTs

Ph

(130)

NAd+ SbCl6–N

Ph

Ph

(131)

N

MeO

NHAd+ SbCl6–

Ph

Ph

(132)

"iii# From carbodiimides

N\N ?!Disubstituted isoureas can be formed by the addition of alcohols or phenols to carbodi!imides[ The reaction can be catalysed by bases but also goes well in the presence of copper"I#chloride\ which allows even hindered alcohols to react[ Thus\ a range of alcohols can be added todiisopropylcarbodiimide in the presence of CuCl to give the isoureas ROC"�NPri#NHPri in highyield ð76TL3334Ł[ The reaction is useful because it converts the oxygen function into a good leavinggroup[ This application is illustrated by the reaction of "S#!octan!1!ol and dcc\ which gave theisourea with retention of con_guration "Scheme 23#^ the leaving group can then be displaced withinversion of con_guration ð80S354Ł[

C6H13 OH

H

C6H13 O

H

C6H13 OH

H

NC6H11

NHC6H11dcc, CuCl

90%

i, AcOH

ii, NaOH

Scheme 34


Isoureas with one or more hydrogen atoms attached to nitrogen can be functionalised using acylchlorides and alkanesulfonyl chlorides ð72HOU"E3#476Ł[ Other types of electrophilic substitutionhave been reported^ thus\ MeOC"1NH#NH1 can be selectively mono! and dichlorinated by reactionwith sodium hypochlorite ð70JOC4937Ł and the isourea "022# reacted with thionyl chloride to givethiatriazine S!oxide "023# ð74TL0094Ł[ There are also several examples of intramolecular N!alkylationof isoureas ð77CC0064\ 78CC341Ł[

TMS-N

N

N-TMS

Me

OArArO

(133) Ar = 4-MeC6H4

N

N

NS

O

Me

OArArO

(134)

"v# Other methods

Isoureas can be prepared by O!alkylation of ureas using trialkyloxonium tetra~uoroboratesð76CB228Ł[ Some examples of intramolecular O!alkylation have also been reported ð72HOU"E3#476\


78CC341Ł[ Dimethyl formamide diethyl acetal reacts with N!chloroamides to give isoureasRCON1C"OMe#NMe1 ð69CB145Ł[ A series of cyclic isoureas has been prepared using a 0\2!dipolar cycloaddition route "Scheme 24# ð80TL4876Ł[

TMS N NR1

SMe

R2N

OAr

NR1

R2

N NR1

R2

+–CsF ArCHO

Scheme 35

5[19[1[2[1 Iminocarbonyl compounds with one oxygen and one phosphorus function

Compounds of this class have been prepared by nucleophilic displacement of chloride fromcarbonimidic chlorides with a phosphorus function ð60ZOB1044\ 89ZOB111Ł[ An example is thearylhydrazone "024#\ which was prepared from the corresponding chloro compound\ sodium sul_teand HCl ð89ZOB111Ł[

NNHC6H4Br-4

(PriO)2P

HSO2O

O(135)

5[19[1[2[2 Iminocarbonyl compounds with one oxygen and one metalloid or metal function

Oxazoles bearing a trimethylsilyl or a trimethylstannyl function at the 1!position are rep!resentatives of this type ð76JOC2302Ł[ The dihydrooxazole "025# was prepared "69)# from theoxazolinyllithium intermediate "026# and trimethyltin chloride\ but attempts to form the cor!responding trimethylsilyl derivative led only to opening of the ring ð76S582Ł[ The correspondingboron substituted species "027# were generated as intermediates when "026# was treated with tri!alkylboranes ð72SC256Ł[

O

NSnMe3

(136)

O

NLi

(137)

O

NBR3

–

(138)

5[19[1[3 Iminocarbonyl Compounds with One Sulfur and One Other Heteroatom Function

5[19[1[3[0 Iminocarbonyl compounds with one sulfur and one nitrogen function

Compounds of this class are usually referred to as isothioureas^ the parent compound"HS#"H1N#C1NH is named as carbamidothioic acid in Chemical Abstracts[ There are many com!pounds of this type in the literature and by far the most common method of preparation is fromthioureas\ by alkylation or other electrophilic substitution on sulfur[ More highly functionalisedcompounds can be obtained from thioureas by successive substitution on sulfur and on nitrogen[ Areview by Ku�hle ð72HOU"E3#486Ł provides a comprehensive survey of methods of preparation[ Themajor methods are summarised below[



Carbonimidic dichlorides have been used only infrequently as starting materials for isothioureas\because of the problems associated with introducing two nucleophiles successively[ Compounds ofthe type RS"PhNH#C1NSO1Ph have been prepared in moderate yield by successive displacementof chloride by thiols and by aniline ð74M540Ł[ When both nucleophiles are in the same molecule\ aswith 1!aminothiophenol\ the method works well[ If the precursor imidoyl chloride already containsthe sulfur function\ replacement of chloride by a nitrogen nucleophile occurs readily ð80JPR076Ł[The nucleophile is normally a primary or secondary amine but sodium thiocyanate has been usedto prepare compound "028# from the corresponding chloride ð75JOC3932Ł^ benzophenone imine\Ph1C1NH\ has also been used in this type of displacement ð78JOC0074Ł[ The chloride of chloro!formamides is similarly readily replaced by sulfur nucleophiles to give isothioureas[

NBut

SCN

MeS

(139)

"ii# From cyanamides\ carbodiimides or thiocyanates

The addition of sulfur nucleophiles\ usually thiols\ to cyanamides or to carbodiimides producesisoureas "Scheme 25#[ The sulfur function of thiophosphoric diesters "RO#1P"1S#OH also adds tocarbodiimides but the isothioureas so formed are unstable and readily rearrange to thioureasð66JOC2518Ł[ Isothioureas unsubstituted on nitrogen can also be prepared by the addition of aminesto thiocyanates "Scheme 25#[

Scheme 36

NR4

R2R3N

R1S

NR2R3N

• NR4R2N

NR1SR2R3NH

(R4 = H)

R1SH

(R4 = H)

R1SH(R2 = R4, R3 = H)

"iii# From thioureas

A wide range of alkylating agents has been used to convert thioureas bearing one or morehydrogen atom on nitrogen into isothioureas ð72HOU"E3#486Ł[ Alkyl halides are most commonlyused ð77S359Ł but there are many examples of the use of other types of alkylating agent[ Even thetertiary bromide 0!bromoadamantane reacted with thiourea to give the isothiourea "039^ Ad�0!adamantyl# in 10) yield ð81CCC0836Ł[ It is also possible to introduce aryl substituents on sulfur byusing activated aryl halides or arenediazonium salts as electrophiles[ Thioureas can be phos!phorylated on sulfur by reaction with a variety of phosphorus electrophiles ð89ZOB687\ 81IZV314Ł[

NH2+Br–

H2N

AdS

(140)


"iv# From iminodithiocarbonates

Compounds of the type "MeS#1C1NX "X�CN\ COR\ SO1R\ etc[# react readily with nitrogennucleophiles "including amines and sulfonamides#[ Usually one of the sulfur functions can bedisplaced selectively to give an isothiourea\ although the use of nucleophilic amines in excess canlead to the formation of guanidines[ Diamines can give either guanidines or bis"isothioureas# "030#\depending on the dilution ð82BCJ037Ł[ The reaction has proved to be widely used for the preparationof N!cyano substituted thioureas ð73CPB3782\ 77JOC2019Ł[

NSO2ArNH

SMe

NH

(141)

ArSO2N

SMe

( )n

"v# By substitution on nitro`en

Isothioureas with a free NH group can be acylated by a wide range of reagents including acylchlorides\ isocyanates and isothiocyanates ð72HOU"E3#486Ł[

"vi# Cycloaddition methods

A ð1¦1Ł cycloadditionÐcycloreversion method of preparing isothioureas from arenesulfonylisocyanates and dithiocarbamates is illustrated in Scheme 26[ Conjugated isothioureas "031#ð77CPB3644Ł act as dienes and undergo ð3¦1Ł cycloaddition to sulfene "H1C1SO1Ł to give thethiadiazine dioxides "032# ð76TL1530Ł[

S

R1R2N

R3S• O +NArSO2

N

S

O

R1R2NSR3

NSO2Ar

R1R2N

R3S–COS

ArSO2

Scheme 37

N

N

Ar

NMe2

(142)

MeS

N

SO2N

Ar

NMe2

(143)

MeS

5[19[1[3[1 Iminocarbonyl compounds with one sulfur and one phosphorus function

Diazo compounds "033# ð71JOC0173Ł and "034# ð83T2084Ł bearing a sulfur and a phosphorussubstituent have been prepared in good yield from the corresponding methylene compounds bydiazo transfer using tosyl azide and a base[

N2

(MeO)2P

Et2NSO2

O

(144)

N2

(EtO)2P

PhSO2

O

(145)


5[19[1[3[2 Iminocarbonyl compounds with one sulfur and one metalloid or metal function

1!Trimethylsilylthiazole "035# provides an example of this class of compounds ð89PAC532Ł[ Dihy!drothiazoles bearing both trimethylsilyl and trimethylstannyl substituents are also knownð89H"20#0102\ 82H"25#362Ł[ The route to these compounds is illustrated in Scheme 27[ The boroncontaining species "036# has been generated from methyl isocyanide ð61LA"644#56Ł but it is unstableand reacts further to give a zwitterionic 1 ] 0 adduct "Scheme 28#[

(146)

N

S TMS

N

S TMS

RRN

S SnMe3

RR

Me3SnCl R = H, 44% R = H, 42%R = Me, 53%

N

S

RR N

S Li

RR

SLi

NCRR

S-TMS

NCRR

TMS-ClBuLi

120 °C

Scheme 38

N

Et2BS

BEt2

PhS

Ph

R

MeNC + Et2BSPh NMe

Et2B

PhS Et2BSPh

91%

+

+– –

Scheme 39

(147)

5[19[1[4 Iminocarbonyl Compounds with One Selenium and One Other Heteroatom Function

Compounds of the type R0Se"R1R2N#C1NR3 are isoselenoureas[ Although not as numerous asisothioureas\ they can be prepared by analogous methods[ The most common method of preparationis the alkylation of selenoureas ð51JOC1788\ 67JHC362\ 75NJC40\ 78MI 519!90Ł[

An intramolecular addition of an amine to a selenocyanide leads to the formation of a cyclicselenourea "Scheme 39#[ The selenocyanide was generated in situ from 1!aminoethylselenosulfuricacid and cyanide ð54JOC1343Ł[ An intermediate isoselenocyanate is formed by the ring opening ofthe azirine "037# by carbon diselenide "Scheme 30# and its reaction with dimethylamine theniodomethane gives the isoselenourea "038# ð71CB1405Ł[

H2NSeSO3H

N

SeNH2

H2NSeCN

CN–

Scheme 40

N

NMe2

N

NMe2

Se Se–

Se

•N

Me2N

Se

O

N

Me2N

SeMe

NMe2

+

(149)

CSe2

i, Me2NHii, MeI

(148)Scheme 41


6.21Functions Containing anIminocarbonyl Group and AnyElements Other Than a Halogenor ChalcogenIAN A. CLIFFEWyeth Research (UK), Taplow, UK

5[10[0 IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE NITROGENFUNCTION "AND NO HALOGEN OR CHALCOGEN FUNCTIONS# 539

5[10[0[0 Iminocarbonyl Derivatives with Two Nitroèn Functions 5395[10[0[0[0 N!Unsubstituted iminocarbonyl derivatives 5395[10[0[0[1 N!Alkyliminocarbonyl derivatives 5315[10[0[0[2 N!Alkenyliminocarbonyl derivatives 5335[10[0[0[3 N!Aryliminocarbonyl derivatives 5335[10[0[0[4 N!Alkynyliminocarbonyl derivatives 5355[10[0[0[5 N!Acyliminocarbonyl derivatives 5355[10[0[0[6 N!Cyanoiminocarbonyl derivatives 5365[10[0[0[7 N!Haloiminocarbonyl derivatives 5375[10[0[0[8 N!Chalcoènoiminocarbonyl derivatives 5495[10[0[0[09 N!Aminoiminocarbonyl derivatives 5425[10[0[0[00 N!P\ N!As\ N!Sb and N!Bi iminocarbonyl derivatives 5445[10[0[0[01 N!Si\ N!Ge and N!B iminocarbonyl derivatives 545

5[10[0[1 Iminocarbonyl Derivatives with One Nitroèn and One P\ As\ Sb or Bi Function 5455[10[0[1[0 N!Alkylimino derivatives with one P or As function 5465[10[0[1[1 N!Arylimino derivatives with one P function 5465[10[0[1[2 N!Acylimino derivatives with one P function 5475[10[0[1[3 Hydrazono derivatives with one P function 5485[10[0[1[4 Diazonium derivatives with one P function 5595[10[0[1[5 N\N!Dialkyliminium derivatives with one P function 559

5[10[0[2 Iminocarbonyl Derivatives with One Nitroèn and One Metalloid Function 5505[10[0[2[0 Silicon derivatives 5505[10[0[2[1 Boron derivatives 551

5[10[0[3 Iminocarbonyl Derivatives with One Nitroèn and One Metal Function 5525[10[0[3[0 Group 07 transition!metal derivatives 5525[10[0[3[1 Other metal derivatives 553

5[10[1 IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE P\ As\ SbOR Bi FUNCTION "AND NO HALOGEN\ CHALCOGEN OR NITROGENFUNCTIONS# 554

5[10[1[0 Iminocarbonyl Derivatives with One P\ As\ Sb or Bi Function and One P\ As\ Sb or Bi Function 5545[10[1[0[0 Iminocarbonyl derivatives with one P function and one P\ As\ Sb or Bi function 5545[10[1[0[1 Iminocarbonyl derivatives with one As\ Sb or Bi function and another As\ Sb or Bi function 557

5[10[1[1 Iminocarbonyl Derivatives with One P\ As\ Sb or Bi Function and One Si\ Ge\ or B Function 5575[10[1[1[0 Iminocarbonyl derivatives with one P function and one Si\ Ge or B function 5575[10[1[1[1 Iminocarbonyl derivatives with one As\ Sb or Bi function and one Si\ Ge or B function 558

5[10[1[2 Iminocarbonyl Derivatives with One P\ As\ Sb and Bi Function and One Metal Function 569

528

539 Iminocarbonyl and Any Other Elements

5[10[1[2[0 Iminocarbonyl derivatives with one P function and one metal function 5695[10[1[2[1 Iminocarbonyl derivatives with one As\ Sb and Bi function and one metal function 560

5[10[2 IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE METALLOIDFUNCTION "AND NO HALOGEN\ CHALCOGEN\ OR GROUP 4 ELEMENTFUNCTIONS# 560

5[10[2[0 Iminocarbonyl Derivatives with Two Metalloid Functions 5605[10[2[0[0 N!Unsubstituted iminocarbonyl derivatives 5605[10[2[0[1 N!Alkyl! and N!aryliminocarbonyl derivatives 5605[10[2[0[2 N!Haloiminocarbonyl derivatives 5615[10[2[0[3 N!Aminoiminocarbonyl "diazomethane# derivatives 5615[10[2[0[4 N!Silyliminocarbonyl derivatives 562

5[10[2[1 Iminocarbonyl Derivatives with One Metalloid Function and One Metal Function 5635[10[2[1[0 N!Alkyl! and N!aryliminocarbonyl derivatives 5635[10[2[1[1 N!Aminoiminocarbonyl "diazomethane# derivatives 563

5[10[3 IMINOCARBONYL DERIVATIVES CONTAINING TWO METAL FUNCTIONS 564

5[10[0 IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE NITROGENFUNCTION "AND NO HALOGEN OR CHALCOGEN FUNCTIONS#

5[10[0[0 Iminocarbonyl Derivatives with Two Nitrogen Functions

Iminocarbonyl derivatives with two nitrogen functions are called guanidines[ Common methodsof preparation of this class of compounds are shown in outline in Scheme 0[ The following sectionsare ordered by type of substituent on the imino N1!atom[

S

NR2R3

NR4R5

X

NR2R3

NR4R5

O

NR2R3

NR4R5

N

NHR3

NR4R5

R1

N

NR2R3

NR4R5

R1

N

NR3

NR4R5

R1

H

N

Cl

Cl

R1

(3)

+MeI (or Me2SO4)or COCl2

X = MeS, Cl

MeI or COCl2 or POCl3

X = MeO, Cl, Cl2PO2

(1) (2)

N C N

R2

R3

i R1NH2

(4)

R2Hal

v

R2 = H

N • N

R1

R2

(5a) (5b) (6)

i, R2R3NHii, R4R5NH

ii

(7)

R4R5NH

iv

(8)

R4R5NH

iii

i, S -methylisothiouronium, O-methylisouronium, O-phosphorylisouronium or chloroformamidinium salts; ii, carbonimidic dichlorides; iii, carbodiimides; iv, cyanamides; v, guanidines

Scheme 1

5[10[0[0[0 N!Unsubstituted iminocarbonyl derivatives

The preparation of guanidine "4a^ R0ÐR4�H# ð72HOU"E3#597\ 80MI 510!90Ł and biguanide "4a^ R0ÐR3�H\ R4�C"1NH#NH1# ð48JA2617\ 50CRV202Ł will not be discussed here[


"i# N!Unsubstituted iminocarbonyl derivatives from amidinium salts and urea derivatives

The reaction of amines with S!methylisothiouronium salts "1^ X�MeS# produces guanidiniumsalts in high yields "Scheme 0\ i#[ Common variants of this classic reaction\ known as the Rathkeguanidine synthesis ð0773CB186Ł\ involve the use of O!methylisouronium\ O!phosphorylisouroniumand chloroformamidinium "Vilsmeier# salts in place of S!methylisothiouronium salt[ The methodproduces a wide range of substituted guanidines and is particularly suitable when ammonia andprimary alkylamines are used as nucleophiles ðB!82MI 510!90Ł[ The reaction with secondary aminesis generally less facile than with primary ð52JMC164Ł\ whilst hindered amines such as t!butylaminefail to react ð53CPB835Ł[ 0!t!Butylguanidine "4b^ R0�But\ R2ÐR4�H# may\ however\ be preparedin 49) yield by using the more reactive zwitterionic aminoiminomethane sulfonic acid "1^ X�SO2

−\R1ÐR4�H# as the electrophile[ This reagent converts primary amines to guanidine derivatives inhigh yields under mild conditions at room temperature ð77TL2072\ 81JCS"P0#2068Ł and has the advan!tage over the Rathke procedure of not producing unpleasant methanethiol as a by!product[ Ther!mally stable N!substituted aminoiminomethanesulfonic acids "1^ X�SO2

−\ R1�alkyl\ R2ÐR3�H\alkyl# are prepared by direct oxidation of thioureas "0^ R1�alkyl\ R2ÐR3�H\ alkyl# with peracidsin the absence ð75S666Ł or presence ð75JOC0771Ł of sodium molybdate as catalyst[ Vilsmeier saltsare also more reactive than isothiouronium salts and the highly hindered 0\0\2\2!tetra!isopropylguanidine "4a^ R0�H\ R1ÐR4�Pri# is obtained in 70) yield by treating the Vilsmeier salt"1^ X�Cl\ R1ÐR4�Pri# with ammonia ð71JCS"P0#1974Ł[

Other variants of the Rathke synthesis utilise heteroaromatic species as leaving groups[2\4!Dimethyl!0H!pyrazole!0!carboxamidine nitrate "1^ X�2\4!Me1!pyrazol!0!yl\ R1ÐR4�H#ð42JA3942\ 47CJC0430Ł and 0H!pyrazole!0!carboxamidine hydrochloride "1^ X�pyrazol!0!yl\ R1ÐR4�H# ð81JOC1386Ł both appear to be superior to S!methylisothiouronium sulfate as guanylatingagents for the preparation of monoalkylguanidines "4b^ R0�alkyl\ R2ÐR4�H#[ The second reagentis the more reactive of the two\ producing products which can be puri_ed by simple crystallisation\but both reagents are poor for preparing guanidine derivatives of sterically hindered\ more basicsecondary amines[ However\ the use of heteroaromatic leaving groups has been extended by the_nding that N\N ?!bisurethane!protected carboxamidines are a very reactive species "Scheme 1^R0�t!butoxycarbonyl "t!BOC# PhCH1OCO#] in reactions with weak nucleophiles such as 1\1\1!tri~uoroethylamine or aniline they give high yields of guanidines after deprotection "using TFA forR0�t!BOC and catalytic hydrogenation for R0�PhCH1OCO#[ This observation indicates that theelectrophilicity of neutral diacylated derivatives is greater than that of protonated unacylatedanalogues ð82TL2278Ł[ Pyrazole!containing guanylating agents show utility as reagents for theconversion of ornithine to arginine in solid!phase peptide synthesis ð82SC546Ł[

N

N

R2

R1 H

N

H

R1

N

N

R2

H H

N

H

H

deprotectR2NH2, THF, 22 °C

Scheme 2

N

NR1

N

H

R1

N

N!Unsubstituted iminocarbonyl derivatives may be prepared directly and in good yields by thetreatment of thiourea derivatives "0# with ammonia in the presence of zinc"II# or preferably lead"II#salts "e[g[\ PbO# with concomitant formation of metal"II# sul_des ð57JMC0157Ł[

0\2!Dialkylguanidines are prepared from 0!alkylthiourea derivatives by formation of a 0!alkyl!2!t!BOC!thiourea\ reaction with an alkylamine in the presence of a water!soluble carbodiimide "WSC#\and deprotection "Scheme 2# ð81TL4822Ł[ 0!Alkylguanidines are obtained in an analogous fashionfrom 0\2!di!t!BOC!thiourea[

S

NHR1

NH2

S

NHR1

NHBOC

HN

NHR1

NHR2

NaH, BOC2O

>82%

i, R2NH2, WSC, DMF >80%

ii, HCl or TMS-OTf

Tf = trifluoromethanesulfonyl

Scheme 3


"ii# N!Unsubstituted iminocarbonyl derivatives from cyanamides

The preparation of 0!alkyl! and 0\0!dialkylguanidines "4a^ R0ÐR2�H\ R3\ R4�H\ alkyl# by thereaction of amine salts with cyanamide "6^ R1�R2�H# in aqueous or alcoholic solution gives lowyields "9Ð19)# of products "Scheme 0\ iv#[ The reaction only works well when metal "e[g[\ calcium#cyanamides are fused with alkylammonium salts ð47CJC0430Ł[ A far more important and widelyused preparative reaction is that of a mono! or dialkylamine base or salt with a monoalkylcyanamide"6^ R1�H\ R2�alkyl#\ which gives 0\0!di and 0\0\1!trialkylguanidines "4a^ R0�R1�H\R2�R3�alkyl\ R4�H\ alkyl# in high yields over a wide temperature range "9Ð079>C# ð57JMC0018\72HOU"E3#597Ł[

0!Cyano!2H!guanidines such as 0!cyano!0\2\2!triethylguanidine are obtained when N!alkyl!dicyanamides are treated with dialkylamines at room temperature "Scheme 3^ R0�R1�Et# but\ onstanding\ they decompose into a mixture of mono! and dialkylcyanamides ð62TL2542Ł[

Scheme 4

NCN

CN

R1N

N

N

R1

CN

R2

R2

HNC N

R2

R2

+ N CN

H

R1R2

2NH, Et2O slow decomposition

"iii# N!Unsubstituted iminocarbonyl derivatives from `uanidines

The alkylation of unsubstituted guanidine with simple alkyl halides usually gives multicomponentmixtures "Scheme 0\ v#[ The few reports of good yields of monoalkylated products include thereaction of guanidine with tosylates in the presence of sodium hydride "Equation "0## ð54JMC335Łand the reaction of 1!"arylamino#imidazolines with alkyl halides "Equation "1##\ which gives exocyclicN!alkylation with Na1CO2 or NEt2 as base\ and endocyclic N!alkylation with NaH ð79JMC0106Ł[

H2N N

NH2+ Cl–

NH2 O

OTsO

+

O

ON

H

HN

NH2

2 NaH, ButOH, reflux(1)

N

N

N

H

Ar

H

N

N

N

R

Ar

H

N

N

N

H

Ar

R

RHal+ (2)

The reaction of guanidines with aryl halides occurs only when the aromatic group is eitheractivated by electron!withdrawing substituents ð53RTC0294Ł or is itself an electron!de_cient hetero!cycle ð51JOC1493Ł "Scheme 0\ v^ R0\ R2ÐR4�H\ R1�1\3!"NO1#1C5H2 or 2!NO1!pyridin!1!yl\ respec!tively#[ An alternative method involving the electrophilic substitution of benzene withhydroxyguanidine!O!sulfonate requires Lewis acid catalyst activation "Equation "2## ð56ZN"B#719Ł[

(3)AlCl3

+H2N

NHOSO3–

NH2

+

HN

N

NH2

H

PhPhH

5[10[0[0[1 N!Alkyliminocarbonyl derivatives

"i# N!Alkyliminocarbonyl derivatives from amidinium salts and urea derivatives

There are many examples of the Rathke synthesis of N!alkylguanidines from S!alkyl!isothiouronium salts "1^ X�SMe\ SEt# and product yields are usually excellent "Scheme 0\ i#ð72HOU"E3#597\ 82MI 510!90Ł[ Preparation from ureas may also be carried out conveniently via


O!alkylisouronium "1^ X�OMe# ð47CJC0430\ 58JMC601Ł or O!phosphorylisouronium salts "1^X�Cl1PO1# ð76CJC515Ł\ but the preferred method\ via the reactive chloroformamidinium "Vilsme!ier# salts "1^ X�Cl#\ permits the preparation of sterically hindered pentaalkylguanidines "4a^ R0ÐR4�alkyl# ð73LA097\ 74LA1067\ 89T0728Ł and highly hindered analogues "e[g[\ 4a^ R0�But\ R1ÐR4�Pri# ð71JCS"P0#1974Ł[ The direct reaction of thioureas "0# with alkylamines in hot ethanolproduces good yields of guanidines "4a^ e[g[\ R0�methyl\ R1ÐR4�H# in the presence of lead oxideð58JMC447Ł[

"ii# N!Alkyliminocarbonyl derivatives from carbonimidic dihalides

Tri!\ tetra! and pentaalkylguanidines are obtained from the reaction of carbonimidic dichloride"5# with two molar equivs of the same amine or one each of two di}erent amines ð58AG"E#19Ł"Scheme 0\ ii#[ An example of the reaction of a carbonimidic di~uoride is provided by per~uoro!1!azapropene "CF2N1CF1#\ which reacts with various dialkylamines such as dimethylamine ð67MI501!90Ł and TMS diethylamide ð81IC377Ł to give 1!tri~uoromethylguanidines "4a^ R0�CF2\ R1ÐR4�Me\ Et#[

"iii# N!Alkyliminocarbonyl derivatives from carbodiimides

The reactions of N\N?!dialkylcarbodiimides "7^ R0\ R1�alkyl# with ammonium or mono! anddialkylammonium salts at room temperature give high yields of di!\ tri! or tetraalkylguanidines "4a^R0�R1�alkyl\ R2�H\ R3\ R4�H\ alkyl# "Scheme 0\ iii# ð51JA2562Ł[

Carbodiimides of type ButN1C1NCHR01 "8^ R0�But\ NMe1# react with NBS to a}ord unstable

alkylidenecyanamidinium bromides "09^ R0�But\ NMe1\ X�Br# which undergo von Braun elim!ination of ButBr to give alkylidenecyanamides "01^ R0�But\ NMe1# "Scheme 4#[ Treating thealkylidenecyanamide "01^ R0�But\ NMe1# with t!butyl chloride and antimony pentachloride pro!duces the stable hexachloroantimonate "09^ R0�But\ NMe1\ X�SbCl5# in quantitative yield andthis reacts with amines to give alkylideneuronium salts "00^ R0�But\ NMe1# ð73CB491Ł[

N • NBut

R1

R1

N

R1

R1

NBut

N

N

N

R1

R1

But

H

H

But

N

R1

R1NC

(9)

NBS, CCl4, refux(11)X–

(10)

ButNH2, CH2Cl2–50 °C, X = SbCl670%

(12)

–ButX, X = Br, 70%

ButCl, SbCl5, CH2Cl2–30 °C, 100%

Scheme 5

+

"iv# N!Alkyliminocarbonyl derivatives from cyanamides

Reactions of amines or amine salts with alkylcyanamides at room temperature give high yieldsof guanidines "Scheme 0\ iv# ð72HOU"E3#597Ł[ A particularly mild method performed at very lowtemperatures involves the reaction of cyanamidinium hexachloroantimonates with ammonia ormono! or dialkylamines "Scheme 5^ R1�R2�alkyl\ R3\ R4�H\ alkyl# ð73CB0050Ł[

NC N

R2

R3

N

R2

R3

N N

N

N

R2

R3

R5

R4

But+

SbCl6–

Scheme 6

i, SbCl5, CH2Cl2, –78 °Cii, ButCl, CH2Cl2, –15 °C

>90%

R4R5NH, CH2Cl2, –78 °C

>90%But + HSbCl6


"v# N!Alkyliminocarbonyl derivatives by miscellaneous methods

Complexes of mercury"II# chloride and t!butyl isocyanide react with an excess of mono! anddialkylamines to give guanidine derivatives and mercury through a redox decomposition reaction"Equation "3#^ R1�Bu\ R2�H or R1�R2�Et#[ The reaction with weak nucleophiles "e[g[\ aniline#is enhanced by the addition of strong bases "e[g[\ triethylamine# and a mechanism for the reactionhas been proposed ð64JOM"83#222Ł[

N

N

N

R2

R3

R2

R3

But

(4)3R2R3NH, THF, reflux

[–Hg, –R2R3NH2+ Cl–]

>39–70%

But N C•HgCl2 •HCl

Lithium aluminum hydride reduction of various alkyl!substituted acylguanidines "4a^ R0�acyl\R1ÐR4�H\ alkyl# gives alkylguanidines in yields ranging from 40) to 51)[ The rate of the reactiondepends on the number of NH atoms\ and yields are improved by using excess reducing agent inTHF at room temperature ð66JOC2597Ł[

5[10[0[0[2 N!Alkenyliminocarbonyl derivatives

"i# N!Alkenyliminocarbonyl derivatives from amidinium salts

Ketone imines react with Vilsmeier salts to give amino!substituted enimines "Equation "4#^ R�H\Me# ð64C403Ł[

R Ph

NH

R Ph

N

NMe2

NMe2(Me2N)2C+Cl Cl–, 2NEt3, CH2Cl2, reflux

R = Me, 52%; R = H, 55%(5)

"ii# N!Alkenyliminocarbonyl derivatives from `uanidines

0\0\2\2!Tetramethylguanidine reacts with isobutyraldehyde or with dimethyl acetylenedi!carboxylate to give amino!substituted enimines "Scheme 6#[ The former reaction fails with aldehydesbearing one or no a!substituent\ and yields in the latter reaction are often poor owing to the base!sensitive nature of the acetylene ð64C403Ł[

N

NMe2

NMe2 HN

NMe2

NMe2MeO2C N

NMe2

NMe2

CO2MeMe2CHCHOTsOH (cat.)

62%

CO2MeMeO2CEt2O, –10 °C

20%

Scheme 7

5[10[0[0[3 N!Aryliminocarbonyl derivatives

The methods of synthesis of N!aryliminocarbonyl derivatives "i[e[\ 1!arylguanidines# are essen!tially the same as those used for 1!alkylguanidines[

"i# N!Aryliminocarbonyl derivatives from amidinium salts and urea derivatives

Although anilines are less nucleophilic than alkylamines they will react with S!alkyl!isothiouronium salts "Scheme 0\ i# to give 1!arylguanidines "4a^ R0�aryl# ð55BSF62Ł\ and high yieldsof 1!phenyl!0\0\2\2!tetrabutylguanidine "4a^ R0�Ph\ R1ÐR4�Me# have been obtained from the


reaction of aniline with chloroformamidinium "1^ X�Cl\ R1ÐR4�Me\ yield�73)# ð89T0728Ł andO!phosphorylisouronium salts "1^ X�Cl1PO1\ R1ÐR4�Me\ yield�35)# ð50CB1167Ł[ 1!"Arylimino#tetrahydroimidazoles such as clonidine "4a^ R0�1\5!Cl1C5H2\ R1�R3�H\R2R4�"CH1#1# are prepared by the reaction of "a# S!methylisothiouronium salts "1^ X�SMe\R1�aryl\ R2ÐR4�H# with ethylenediamine ð67RTC40Ł^ "b# sulfonic acid derivatives "1^ X�SO2

−\R1�R3�H\ R2R4�"CH1#1# with anilines ð75JOC0771Ł^ and "c# the complex formed from 0!acetyl!imidazolidinone and phosphorus oxychloride "1^ X�Cl1PO1\ R1�H\ R3�MeCO\R2R4�"CH1#1# with anilines followed by deacylation ð79AF0622Ł[

The transimination reaction of N!arylphosphimides with thioureas gives 1!arylguanidines in highyield "Equation "5## ð80MIP43525Ł[

BuS

O2N N PPh3

+S

N

NHCO2Me

H

SO3H

PhH, reflux

91%

BuS

O2N N

N

NHCO2Me

H

SO3H

(6)

"ii# N!Aryliminocarbonyl derivatives from carbonimidic dichlorides

The stepwise replacement of the two chlorine atoms of the N!arylcarbonimidic dichloride "5^R0�3!NCC5H3# by two di}erent monoalkylamines gives 0\2!dialkyl!1!arylguanidines "4a^ R0�3!NCC5H3\ R1�R3�alkyl\ R2�R4�H# in high yields "Scheme 0\ ii# ð81SC0080Ł[ The reactionof N!phenylcarbonimidic dichloride with TMS!dialkylamides gives high yields of intermediate chloro!formamidines which react further\ only in the case of sterically unhindered chloroformamidines"Scheme 7^ R0�Me# and TMS!dimethylamide\ to give 0\0\2\2!tetramethyl!1!phenylguanidine"R0�R1�Me# ð58TL0310Ł[ Organothallium amides "Me1TlNMe1# undergo related reactionsð62ZC081Ł[ The reaction of N!"1\3!dichlorophenyl#carbonimidic dichloride "5^ R0�1\3!Cl1C5H2#with ethylenediamine gives clonidine "4a^ R0�1\5!Cl1C5H2\ R1�R3�H\ R2R4�"CH1#1#ð67RTC40Ł[

PhN

Cl

Cl

PhN

NR12

Cl

PhN

NR12

NR22

TMS-NR12, 85 °C, 24 h

–TMS-ClR1 = Me, Et, Pr

54–84%

TMS-NR22, 85 °C, 24 h

–TMS-ClR1 = R2 = Me

98.5%

Scheme 8

"iii# N!Aryliminocarbonyl derivatives from carbodiimides

1!Aryl!0\2!disubstituted guanidines are prepared in good yields from N\N?!disubstituted car!bodiimides and anilines in the absence of solvent with or without heating^ in re~uxing toluene^ orin DMF at room temperature in the presence of sodium hydride "Scheme 0\ iii# ð79JMC02Ł[

"iv# N!Aryliminocarbonyl derivatives from cyanamides

Arylcyanamides "6^ R1�H\ R2�aryl# react with ammonia and primary amines "Scheme 0\ iv# inmethanol at 099>C in a steel bomb to give 1!arylguanidines "4b^ R0�R3�H\ R2�aryl\ R4�H\alkyl# in reasonable yields "31Ð74)# ð64JMC89Ł[


"v# N!Aryliminocarbonyl derivatives by miscellaneous methods

Triarylguanidines are obtained in good yield by the reaction of anilines with 1\1!dichloro!0\2!benzodioxole "Equation "6## ð53LA"564#031Ł[

(7)O O

Cl Cl

PhN

NHPh

NHPh

5 PhNH2, THF, reflux

97%

5[10[0[0[4 N!Alkynyliminocarbonyl derivatives

1!"Phenylethynyl#!0\0\2\2!tetramethylguanidine is formed as a transient intermediate in the ~ashphotolysis of phenylguanidinocyclopropenones "Scheme 8#[ An acylguanidine is the _nal productin aqueous solution ð80AG"E#0245Ł[

N NMe2

NMe2

Ph

O

NPh

NMe2

Me2N

N

NMe2

NMe2

Ph

Ohν, H2O

–CO

H2O

Scheme 9

5[10[0[0[5 N!Acyliminocarbonyl derivatives

The tautomerism of monoacylguanidines has been studied ð50CJC0906Ł[

"i# N!Acyliminocarbonyl derivatives from S!methylisothiourea

Acylation of the free base of S!methylisothiouronium salts "1^ X�SMe\ R1�alkyl\ R2ÐR4�H#with acid chlorides followed by treatment of the resulting S!methyl!N!acylthioureas with appropriatemonoalkylamines gives 0!acyl!1\2!dialkylguanidines "4a^ R0�R1�alkyl\ R2�R3�H\ R4�acyl#ð64AF0366Ł[

"ii# N!Acyliminocarbonyl derivatives from cyanamides

The reaction of N\N!dialkylcyanamides with acid chlorides gives acylated chloroformamidiniumsalts which on reaction with secondary amines produce acylated guanidines "Scheme 09^ R�Me\Et\ allyl# ð70MI 510!90Ł[

Scheme 10

N

NR2

NR2

C4F9

O

N

NR2

Cl

C4F9

O

NC NR2

C4F9COCl

72–94%

R2NH

51–57%

"iii# N!Acyliminocarbonyl derivatives from `uanidines

Unsubstituted and monosubstituted guanidines are acylated by condensation of the requisiteguanidine free base with the appropriate acid ester ð50CJC0906\ 64AF0366Ł[ The preparation of di!and trisubstituted guanidines takes longer and in these cases acylation of guanidines with acidchlorides or anhydrides is the normal practice ð57JOC441Ł\ although mixtures of products invariably


result ð64AF0366Ł[ Di! and triacylated guanidines have been deacylated selectively to give monoacyl!guanidines with either ethanol or a quaternary ammonium hydroxide ion!exchange resinð66JOC2597Ł[

1!Phenyl!0\0\2\2!tetramethylguanidine undergoes exchange reactions with benzoyl and thio!benzoyl isocyanates to give high yields of acylated or thioacylated guanidines "Equation "7##ð67LA0432Ł[

N

NMe2

NMe2

Ph

X

PhN

NMe2

NMe2

PhX

NCO

X = O, S76–93%

(8)

1!"Thiocarbamoyl#guanidines are produced by the reaction of 0\0\2\2!tetramethylguanidine withN\N!dimethylthiocarbamoyl chloride ð61IJS"A#094Ł or isothiocyanates "Equation "8## ð71PIA330Ł[

N

NMe2

NMe2

N

S

HN

NMe2

NMe2R2

R1

ClN

S

R2

R1

(9)

MeCN, refluxR1, R2 = Me, 46%

or

R1NCS, PriOH, 22 °CR1 = Me, Ph; R2 = H

70–90%

1!Amidinoureas "4a^ R0�ArNHCO# are obtained from the reaction of guanidines with arylisocyanates "ArNCO# and:or carbamoyl chlorides "ArNRCOCl# ð67AF0324Ł[

"iv# N!Acyliminocarbonyl derivatives by miscellaneous methods

Carbonic acid ortho!amides react with acid amides to give acylguanidines "Equation "09#^ R�H\Et\ Ph# ð68LA1985Ł[

R

O

NH2

+ PriO

NMe2

NMe2

NMe2 N

NMe2

NMe2

R

O

(10)

5[10[0[0[6 N!Cyanoiminocarbonyl derivatives

"i# N!Cyanoiminocarbonyl derivatives from thioureas and their derivatives

Cimetidine "05^ R�1!""4!methylimidazol!3!yl#methylthio#ethyl# "Scheme 00# is an example of anN!cyanoiminocarbonyl derivative which has been prepared by several methods[ These methodsinclude the reaction of amine "02# with methyl isothiocyanate to give the thiourea "03#\ which istreated with lead cyanamide "i#^ the reaction of amine "02# with N!cyano!N?\S!dimethylisothiourea"ii#^ and the reaction of amine "02# with dimethylcyanodithioimidocarbonate followed by treatmentof the intermediate S!methylisothiourea "04# with methylamine "iii# ð66JMC890Ł[ The Rathke reactionis acid catalysed and so the use of the weak base N!cyano!N?\S!dimethylisothiourea in "ii# leads toa low yield of product[ This limitation has been circumvented by the room temperature reaction ofN!aryl! or N!alkyl!N?!cyanothioureas "0^ R1�R3�H\ R2�CN\ R4�aryl\ alkyl# with monoalkyl!amines in DMF in the presence of a water!soluble carbodiimide\ which gives 1!cyanoguanidines"4b^ R0�alkyl\ R2�CN\ R3�H\ R4�aryl\ alkyl# in a single step in high yields "×54)# ð78TL6202Ł[The reaction works well with sterically hindered t!alkylamines and N\N!dialkylamines and is animprovement over the earlier procedure using dicyclohexylcarbodiimide"dcc# ð73SC0164Ł[ The roomtemperature reaction of cyanamide "R0NH1\ R0�CN# with a range of N!"3!pyridyl#thioureas "0^


R1�R4�H\ R2�3!pyridyl\ R3�Ph\ neopentyl\ etc[# in the presence of dcc also gives 1!cyano!0!"3!pyridyl#guanidines "4b^ R0�CN\ R2�3!pyridyl\ R3�Ph\ neopentyl\ etc[\ R4�H# in good yields"×39)# ð67JMC662Ł[

S

NHR

NHMe

R NH2 N

NHR

NHMe

NC

N

NHR

SMe

NC

MeNCS, EtOH>80%

NNHMe

SMe

NCi

NSMe

SMe

NC

ii

iii

R = N

NH

S

PbNCN, DMF, reflux43%

MeNH2, EtOH90%

Scheme 11

(13)

(14)

(15)

(16)

EtOH, 73%

MeCN, 20%

"ii# N!Cyanoiminocarbonyl derivatives from carbodiimides

The reaction of cyanamide "H1NCN# with carbodiimides gives 1!cyanoguanidines in high yields"Scheme 0\ iii#[ The reaction with hindered carbodiimides "7^ R0�aryl\ R1�t!alkyl# in the absenceof solvent occurs smoothly in the presence of catalytic diisopropylethylamine\ whilst reaction withless!hindered carbodiimides is exothermic ð67JMC662Ł[

"iii# N!Cyanoiminocarbonyl derivatives from cyanamides

The synthesis of monosubstituted 1!cyanoguanidines "4b^ R0�R4�H\ R2�CN\ R3�alkyl# isaccomplished in reasonable yields by the condensation of sodium "or lithium# dicyanamide "6^R1�Na\ R2�CN# with monoalkylammonium salts in either re~uxing t!butanol or water "Scheme0\ iv# ð57JMC700Ł[

A cyanoguanidine is formed from the reaction of N!methyl!N!phenylcyanamide with sodium"Equation "00##[ The reaction is highly dependent on the nature of the nitrogen substituents andproceeds via an electron transfer mechanism involving the formation of a catalytic quantity ofPhMeN− ð80CJC750Ł[ The same product is formed in a multistep sequence from the reaction of N!methyl!N!phenylcyanamide with phenyllithium in 47) yield ð60CJC1204Ł[

NC N(Me)Ph N

N(Me)Ph

N(Me)Ph

NCNa, PhMe

61%(11)

5[10[0[0[7 N!Haloiminocarbonyl derivatives

The most common method of preparation of N!haloiminocarbonyl derivatives "N!halo!guanidines# is the elemental halogenation of appropriately substituted guanidines[ It should be


noted that many N!haloguanidines are unstable and:or explosive and consequently most halo!genations in the laboratory are carried out on a small scale and with appropriate shielding andprotective equipment[ The issue of tautomerism and double bond isomerism in unsymmetricalcompounds has been studied ð56TL2740Ł[

Per~uoroguanidine is produced by the reaction of guanidine salts with elemental ~uorine eitherin aqueous solution ð64USP2857047Ł or in the absence of solvent but in the presence of alkali metal~uorides as diluents ð56JOC0551\ 56JOC2748Ł "Equation "01##[ The latter technique has been extendedto the direct ~uorination of cyanoguanidine in the presence of a large amount of sodium ~uoride"Equation "02## ð57JOC1411Ł[ In a similar way\ guanidine nitrate has been chlorinated to give a 26)yield of perchloroguanidine using a two!phase system consisting of water and chloroform in thepresence of _nely divided marble and NaCl at −09>C "Equation "03## ð70MI 510!91Ł[ Fluorinationof monoalkoxycarbonylguanidines gives tetra~uoro derivatives "Equation "04##\ whilst ~uorinationof 0\2!bis"alkoxycarbonyl#guanidines gives not only the expected ~uorinated product\ but alsoproduces some ~uorinolysis of the alkoxycarbonyl groups so that bis"alkoxycarbonyl#~uoro!guanidines and alkoxycarbonyltetra~uoroguanidines are both formed "Equation "05## ð58JOC1739Ł[1!Chloro! and 1!bromotetramethylguanidines are prepared by the direct halogenation of 0\0\2\2!tetramethylguanidine "Equation "06#^ Hal�Cl\ Br# ð55JOC0315Ł[

(12)HN

NH2

NH2

FN

NF2

NF2

excess F2

HN

N

NH2

FN

N

NF2

excess F2, NaFCN

H

CF2NF2

F

(13)

(14)HN

NH2

NH2

ClN

NCl2

NCl2

excess Cl2

marble, NaCl

HN

N

NH2

H O

ORexcess F2

FN

N

NF2

F O

OR(15)

HN

N

N

H O

OR excess F2

H

O

RO

FN

N

N

F O

ORF

O

RO

FN

N

NF2

F O

OR(16)+

(17)HN

NMe2

NMe2

Hal2HalN

NMe2

NMe2

1!Chloro!0\0!dialkylguanidines may be prepared by an oxidation route in which the appropriateunchlorinated guanidine salt is reacted with sodium hypochlorite in a two!phase solvent system atlow temperature "Equation "07#^ X�Cl\ NO2\ SO3#[ 0!Aryl!1!chloroguanidines "Equation "07#^R0�Ph\ R1�H# are obtained in low yields "³09)# by this route owing to oxidative side reactions^however\ if the possibility of the interfering aromatic quinone!type intermediates is eliminated"because\ e[g[\ R0�Ph\ R1�Me#\ then 1!chloro derivatives are obtained in high yieldsð54ZN"B#0054Ł[

(18)HN

NR1R2

NH2

ClN

NR1R2

NH2

•HXNaOCl, –5 °C, H2O–Et2O


An example where a 1!haloguanidine is not prepared by the formation of a nitrogen0halogenbond is the reaction of an amine with an N!~uoroimine] the reaction of electron!de_cientpenta~uoroguanidine with alkyl! or arylamines at low temperatures gives an adduct which onwarming loses di~uoroamine to yield a tri~uorinated product "Scheme 01#[ The rate of reaction andthe type of product formed depends upon the nucleophilicity of the amino component ð62JOC0964Ł[

FN

NF2

NF2

FN

NF2

NR1R2

R1R2NH, –110 °C –HNF2, 25 °CFHN

NF2

NF2

NR1R2

Scheme 12

5[10[0[0[8 N!Chalcogenoiminocarbonyl derivatives

"i# Oxy`en derivatives

The most common methods of synthesis of hydroxyguanidines involve the reactions of N!substituted or unsubstituted hydroxylamines with S!alkylisothioureas ð56ZN"B#719\ 63JOC0055Ł orchloroformamidines ð57JA5735Ł\ carbodiimides ð61CB0698\ 62ZC47Ł\ and cyanamides "Scheme 02\ "i#Ð"iii#\ respectively# ð55JCS"C#1920\ 69CC795Ł[

N

NR2R3

X

R4NHOH

i

R1

N

NR2R3

N

R1

R4

HO

R4NHOH

iiR3 = H

N • N

R1

R2

H2NOHR1 = R4 = H

NC N

R2

R3

Scheme 13

iii

i, S-alkylisothioureas or chloroformamidines; ii, carbodiimides; iii, cyanamides

X = SR, Cl

Tetrasubstituted hydroxyguanidines are best prepared from chloroformamidinium chlorides viareaction with O!"THP#hydroxylamine followed by removal of the protecting group with acid"Equation "08##[ Cyclic tri! and tetrasubstituted hydroxyguanidines are prepared by the reaction ofphosgene!O!"THP#oxime with a diamine\ followed by removal of the protecting group "Equation"19## ð65JOC2142Ł[ Other methods for the formation of hydroxyguanidine!like compounds employthe reduction of nitro precursors[ Dinitroformaldehyde oxime is formed by the reduction of tri!nitromethane in an acid medium on a mercury cathode "Equation "10## ð64MI 510!90\ 65MI 510!90Ł\and 0\0?!"hydroxyimidoyl#bis"1!aryl#diazenes are produced when 2!nitroformazans are reduced byH1S in aqueous alcoholic ammonia solution at 9>C "Equation "11## ð79MI 510!90Ł[

N

NR1R2

NR3R4

HO

Cl

NR1R2

NR3R4+

i, THP-ONH2, NEt3ii, H3O+

31–65%(19)

N

Cl

Cl

THP-O(CH2)nN

N

N

HO

R1

R2

(20)

i, R1NH(CH2)nNHR2, NEt3ii, 3 mol l–1 HCl

n = 2, 3 31–58%


O2N

NO2

NO2

N

NO2

NO2

HO+2e–, + 2H+

–H2O(21)

N

N

N

HOH2S

N

Ar

N

Ar

O2N

N

N

N

Ar

NHAr

(22)

Alkoxyguanidines are prepared by methods analogous to those used for the hydroxy derivativesabove but with O!alkylhydroxylamines in place of hydroxylamines[ They are also obtained byalkylation of hydroxyguanidines with alkyl bromides or iodides "Scheme 03# ð63JPR323Ł[ Acetoxy!and benzoyloxyguanidines are prepared by acylation of hydroxyguanidines "Scheme 03# ð69BAP458\63JPR323Ł[

N

NR1R2

NR3R4

R5OR5Hal

N

NR1R2

NR3R4

HO

N

NR1R2

NR3R4

O

O

R

Scheme 14

RCOCl

"ii# Sulfur derivatives

Penta~uorosulfenylguanidines are obtained from the reaction of SF4N1CCl1 either with dial!kylamines ð71JFC"08#300Ł or with more nucleophilic dialkylaminosilanes "Equation "12#^ R�alkyl^X�H\ TMS# ð81IC377Ł[ They are also formed by the reaction of guanidine N0H bonds withsulfenyl chlorides ð48CB1452Ł[

(23)N

NR2

NR2

F5SR2NX

R = alkyl; X = H, TMSN

Cl

Cl

F5S

Several methods for the synthesis of sulfonylguanidines are known[ The simplest method employsthe condensation of an arylsulfonyl chloride with guanidine "Equation "13## ð39USP1107389Ł[

(24)N

NH2

NH2

ArO2SH2O–Me2CO, NaOH

HN

NH2•HNO3

NH2

ArSO2Cl +

The Rathke guanidine synthesis using S!methylisothiouronium salts tends to give low yields ofsulfonylguanidines "Equation "14#^ X�SMe# ð62JOC0480Ł\ and so the more reactive amidiniumchlorides are usually employed "Equation "14#^ X�Cl\ R0�Ar\ R1ÐR4�alkyl ð62JOC0480\ 68ZC149Ł^X�Cl\ R0�Me\ R1�Bui\ R2�H\ R3�R4�alkyl ð56AP"299#456Ł^ and X�Cl R0�R1�Ph\ R2ÐR4�H ð63ZOR31Ł#[ Amidinium chlorides will react with a range of nitrogen nucleophiles otherthan amines\ such as sodium azide and hydrazine\ to give sulfonylcarbamimidic azides andN!""dialkylamino#hydrazinomethylene#sulfonamides "Scheme 04^ R1\ R2�Me\ Ph#[ Sulfonyl!carbamimidic azides react with triphenylphosphane to give iminophosphoranes ð71LA1094Ł[ Theleaving!group ability of cyanide has been exploited in a sequence involving the room temperaturereaction of 3!chloro!4!Ts!0\1\2!dithiazole with secondary amines to give N\N!dialkylcyano!formamidines which on heating with excess secondary amine give 1!Ts!tetraalkylguanidines "Scheme05# ð81TL3852Ł[ The aryl! or alkylsulfonyl group can be attached to the nucleophile instead ofthe electrophile as in the reaction of arylsulfonamides with S!alkylisothioureas "Equation "15##ð56AG"E#751Ł[ "Alkylaminosulfonyl#guanidines have been prepared by the reaction of N\N!dialkyl!N?!chlorosulfonylchloroformamidines with primary or secondary amines "Equation "16##ð77JPR899Ł[ N!Sulfonylguanidines are also prepared by the reaction of amines with either S\S!dimethyl!N!arylsulfonyliminodithiocarbonimidate ð55CB1774Ł or N!Ts!carbonimidic dichloride"Equation "17#^ X�MeS\ Cl# ð62JOC0480\ 66AP719\ 68JOC3425Ł[


(25)N

NR2R3

NR4R5

R1O2SR4R5NH

N

NR2R3

X

R1O2S

N

NR2R3

NHNH2

ArO2SH2NNH2

72–86%N

NR2R3

Cl

ArO2S

NaN346–86%

N

NR2R3

N3

ArO2S PPh3

20–86%

AmiONO

N

NR2R3

N

ArO2S

PPh3

Scheme 15

SS

N

TsN Cl

TsN

NR12

CN

TsN

NR12

NR22

R12NH, 22 °C

53–79%

R22NH, CH2Cl2, reflux

40–99%

Scheme 16

TsNH2

41%MeS

N

N

H CO2Me

Ph

TsN

N

N

H CO2Me

PhH

(26)

(27)N

NR1R2

Cl

ClO2S4 R3R4NH

N

NR1R2

NR3R4

R3R4NO2S

(28)N

X

X

RO2S2 R1R2NH

N

NR1R2

NR1R2

RO2S

A further method for the preparation of sulfonylguanidines involves the reaction of either N!sulfonyl!N?!alkylcarbodiimides with alkylamines "Scheme 06\ path "a#^ R0�Ph\ R1�But\R2R3�"CH1#3# ð56AP"299#456Ł or N\N?!dialkylcarbodiimides with sulfonamides "Scheme 06\ path"b## ð69JCS"C#0318Ł[

N

NHR2

NR3R4

R1O2SR3R4NH

path aN • N

R1O2S

R2

N • N

R3

R2

R1SO2NH2

path b

Scheme 17

Finally\ sulfonylguanidines may by prepared by ð1¦1Ł cycloaddition reactions "Scheme 07#involving sulfonyl isocyanates and guanidines "Ar�3!MeC5H3\ X�C\ Y�O\ Z�NPh#ð57AG"E#180Ł^ sulfonyl isocyanates and thioureas "Ar�3!MeC5H3\ X�C\ Y�O\ Z�S# ð80CPB0828\81MI 510!91Ł^ and N!sul_nylsulfonamides and thioureas "Ar�Me\ X�S\ Y�O\ Z�S# ð56ACS0182Ł[In a related reaction\ the crystalline bis"imino#thiazetidine\ formed from the reaction of methyl!t!butylcarbodiimide with tosyl isothiocyanate\ undergoes a reaction with excess dimethylamine at9>C to give a tosylguanidine "Scheme 08# ð70BSB52Ł[

The anion of trinitromethane reacts with soft electrophiles like phenylsulfenyl chloride at thecarbon atom to give C!substituted trinitromethane derivatives "Scheme 19^ M�K\ Ag\ piperi!


N X Y

ArO2S+ Z

NR2

NR2

X

N

ZY

ArO2S NR2

NR2

Scheme 18

N

NR2

NR2

ArO2S

ButN C NMeN C S

Ts+ S

NMeTsN

22 °C

95%NBut

Scheme 19

Me2NH, 0 °C

51% TsN

N

NMe2

Me NHBut

S

dinium# ð63MI 510!91Ł and with hard electrophiles like phenylsulfenyl tetra~uoroborateð64IZV0558Ł\ acetyl chloride ð62IZV708Ł\ or TMS!Cl ð62ZOR785Ł at the oxygen atom to give aci!nitroderivatives "R�PhS\ Ac\ TMS\ respectively#[

PhSCl RXPhS

NO2

NO2

NO2

NO2

NO2

NO2–M+ N

NO2

NO2RO

–O+

Scheme 20

5[10[0[0[09 N!Aminoiminocarbonyl derivatives

"i# Alkyl and aryl derivatives

The methods of synthesis of N!aminoiminocarbonyl derivatives "N!aminoguanidines# are anal!ogous to those used for guanidines and will not be discussed in detail[ Scheme 10 shows the generalmethods of preparation from amidinium salts and hydrazines "i# ð89T2786Ł^ from thioureas andhydrazines "ii# ð99CB0947Ł^ from S!alkylisothiosemicarbazide "salts# and amines "iii# ð69JHC578Ł^from cyanamides and hydrazines "iv# ð69CC795Ł^ from carbodiimides and hydrazines "v# ð55AP698Ł^from S!alkylthiourea "salts# and hydrazines "vi# ð51LA"540#78Ł^ and from N!aminocarbonimidicdichlorides and amines ð61JOC1994Ł or the more reactive silylated amines\ e[g[\ TMS!NMe1 ð81IC377Ł"vii#[ These methods will not be discussed further[ All the theoretically possible methylated amino!guanidines "H1NNRC"1NR1#NR1\ where R�Me or H# have been prepared ð52JMC172Ł[

"ii# Imino\ nitro\ nitroso and azido derivatives

A wide range of imino and nitro derivatives of guanidines have been prepared by the reaction ofaryl diazonium salts with nitroalkyl derivatives "the Bamberger reaction\ ð15LA"335#159Ł[ 0\4!Diaryl!2!nitroformazans "07# are readily obtained by this procedure "Scheme 11#\ and any tendency to tarformation is minimised by keeping the temperature below 9>C\ waiting long enough for the nitrogenoxides to escape after diazotization\ and employing pure nitromethane and freshly distilled aryl!amines ð25JCS0582\ 32JA1289\ 46ZOB1023\ 76POL02Ł[ The reaction of nitromalonyl aldehyde anion "08#with aryl diazonium salts gives analogous products "Scheme 11^ X�Cl\ BF3# ð54ZOR624\ 61ZOR221Ł[Dinitroformaldehyde hydrazones have also been prepared from nitroalkyl derivatives by the con!densation of hydrazines with tetranitromethane at low temperatures "Scheme 12^ R0�R1�Me\ Et\Ph# ð68IZV702\ 80CL458Ł and by the diazo coupling reaction of arylhydrazines with dinitromethane"Scheme 12^ R0�H\ R1�1!3!dinitrophenyl "dnp# ð66ACS"B#478Ł[ The reaction of aromatic diazocompounds with malonic acid instead of a nitroalkyl derivative "Equation "18## gives 0\4!diaryl!2!arylazoformazans ð63MI 510!90Ł via a 0\4!diarylformazan intermediate ð51MI 510!90\ 53ZOB1744Ł[


Cl

N+R3R4

NR5R6

NC N

R5

R6

N

NR3R4

NR5R6

R1R2N

N

NR4

NR5R6

R1R2N

S

NR3R4

NR5R6

N • N

R4

R5

N

NR3R4

SR

R1R2N

RS

NR4

NR5R6

R1R2NNH2

R3 = HR1R2NNH2

ii

N

Cl

Cl

i

R1R2N

ivR1R2NNH2

Scheme 21

R1R2NNH2

v

i, R3R4NHii, R5R6NH

vii

R5R6NHiii vi

R1R2NNH2

H

i, amidinium salts; ii, thioureas; iii, S-alkylisothiosemicarbazides; iv, cyanamides and hydrazines; v, carbodiimides; vi, S-alkylthioureas; vii, dichlorocarbiimides

ArNHN

NO2

N N

Ar

ArNHN

NO2

CHO

MeNO2

(17)

O2N

CHO

CHO

(18) (20) (19)

– Na+2 ArN2

+

13–68%

ArN2+ X–, H2O

>60%

ArN2+ X–, DMF

21–70%

Scheme 22

R1R2N NH2 R1R2NN

NO2

NO2O2N

NO2

N2+

C(NO2)4

40–90%

NO2

NO2

Scheme 23

OH

OH

O

O

N NAr

NArN

ArNHNArN2

+, pH 5–6

18–40%(29)

0\4!Diaryl!2!aminoformazans are prepared by nucleophilic displacement reactions of amines with2!chloro! ð52ZOB002Ł or 2!nitro!0\4!diarylformazans "Equation "29#^ X�Cl\ NO1\ R0\ R1�H\alkyl# ð74JHC702Ł[ In a similar fashion\ N!aryl!0!nitromethanehydrazonyl azides are prepared bythe reaction of sodium azide with bromo derivatives in aqueous alcoholic media "Equation "20##ð61ZOR28Ł\ and a wide range of "heteroarylmethyl#nitroguanidines have been prepared in the patentliterature using the reaction of S!methyl!N!nitroisothioureas with amines "e[g[\ Equation "21##ð80EUP314867Ł[

(30)

NR1R2

NArN

ArNHN

X

NArN

ArNHNHNR1R2

>50%

(31)

NO2

N3

ArNHN

NO2

Br

ArNHNNaN3

47–78%


SMe

NH2

O2NNEtOH, reflux

40%+ S

N

Cl

NMe

HS

N

Cl

N

Me

NH2

O2NN (32)

A kinetic study indicates that the nitration of syn!tetraethylguanidine with nitric acid is 699 timesslower than the nitration of guanidine and occurs in sulfuric acid but not in acetic acid "Equation"22## ð46CJC416Ł[

HN

NEt2

NEt2

O2NN

NEt2

NEt2

HNO3–H2SO4

60%(33)

Most 1!nitrosoguanidines are unstable and decompose to give the corresponding ureas andnitrogen^ however\ the 0\0\2\2!tetraphenyl derivative obtained by nitrosylation of 0\0\2\2!tetra!phenylguanidine is a stable solid at 19>C "Scheme 13# ð63BCJ824Ł[ 2!Nitrosoformazans are obtainedby the reduction of 0\4!diaryl!2!nitroformazans with H1S "Equation "23## ð79MI 510!90Ł[

HN

NR2

NR2

ONN

NR2

NR2

NOCl, CCl4, –20 °C

R = Ph, 92%O

NR2

NR2

Scheme 24

–N2

R ≠ Ph

ArNHN

N

NO2

H2S, EtOH–NH3NAr

ArNHN

N

NO

NAr

(34)

5[10[0[0[00 N!P\ N!As\ N!Sb and N!Bi iminocarbonyl derivatives

"i# Phosphorus"III# derivatives

The few examples of this class of compounds are iminophosphinoguanidines which have beenmade by reaction of iminochlorophosphines with silylated guanidines "Equation "24## ð80ZOB390Ł[Tris"trichlorophosphoranediylamino#carbenium salts are prepared by the photolysis of tri!azidocarbenium hexachloroantimonate in PCl2 "Equation "25## ð68AG"E#582Ł via a mechanism whichis analogous to the Staudinger reaction of organic azides with phosphanes[

TMS-N

NMe2

NMe2

+ But

But

But

N PCl>91%

But

But

But

N P

N

NMe2

NMe2 (35)

Cl3P–N

N

N

PCl3

PCl3

+

SbCl6–N3

N3

N3

+ SbCl6–3 PCl3, hν

–3 N2

(36)

"ii# Phosphorus"V# derivatives

Two major synthetic methods exist for this class of compound[ The _rst route entails formationof the amide bond by the reaction of phosphoryl chlorides with guanidines to give\ e[g[\guanidinylphosphoric diamides "Equation "26## ð56JMC007\ 56JMC162Ł[ The second route involvesthe formation of two guanidinyl C0N bonds by the reaction of dichloromethylenephosphoramidicderivatives with dialkylamines "Equation "27##] thus\ reactions with excess dialkylamines produce


bis"dialkylamino#methylenephosphoramidic esters "X�O\ R0�R1�Me\ Et\ allyl# ð58IZV008Ł andphosphoramidothioic acid derivatives "X�S\ R0�R1�Me\ Et# ð63OMR"5#383\ 63ZOB427Ł\ whilstreactions with two di}erent amines produce mixed amide products "X�O\ R0�Ph\ R1�Et#ð55ZOB350Ł[ A combination of both methods is provided by the reaction of dialkylcyanamides withphosphoryl chloride followed by treatment with dialkylamines "Scheme 14^ R0\ R1�various alkylgroups# ð63ZOB0153Ł[

PCl

OMe2N

Me2N+ HN

NR2

NR2

NR2

NR2

PN

OMe2N

Me2NR = H, 11%R = Me, 31%

(37)

(38)NR1

2

NR22

PN

XEtO

EtOCl

Cl

PN

XEtO

EtO

i, R12NH, NEt3

ii, R22NH, 2 NEt3

>50%

POCl3R1

2NCN

45–75% N

NR12

Cl

P

ClO

ClN

NR12

NR22

P

R22N

O

R22N

R22NH

>50%

Scheme 25

"iii# As\ Sb and Bi derivatives

The single report of guanidines attached to group 04 elements other than N or P refers to dative!bonded complexes of guanidines and bismuth or antimony trihalides ð77EUP162347Ł[

5[10[0[0[01 N!Si\ N!Ge and N!B iminocarbonyl derivatives

N!Silylated guanidines are prepared by treating the corresponding guanidine with a chlorosilanein the presence of a base "Equation "28## ð64ZOR651Ł[ In the absence of added base\ a stableguanidinium salt ""Me1N#1CNHTMS#¦ Hal− is formed ð77JOM"228#130Ł[

HN

NMe2

NMe2

TMS-N

NMe2

NMe2

TMS-Cl, NEt3(39)

The only example of N!germylated or N!borated guanidine derivatives are triarylboron complexes"Equation "39#^ R�H\ Ph# ð67ZOB700\ 70ZOB779Ł[

HN

NHR

NHR

N

NHR

NHR

BAr3

18–99% Ar3B

H(40)

+

–

5[10[0[1 Iminocarbonyl Derivatives with One Nitrogen and One P\ As\ Sb or Bi Function

The majority of compounds in this class contain a phosphorus function[ Very few compoundscontain arsenic functions\ and none contain antimony or bismuth functions[ The compounds willbe discussed in the order of the substituent on the imino nitrogen atom[


5[10[0[1[0 N!Alkylimino derivatives with one P or As function

The starting materials for N!alkyl! and N!arylimino derivatives are either chloroimine analoguesor carbodiimides[ The few examples of N!alkylimino derivatives include compound "11^ R�Bu#\prepared by a MichaelisÐArbuzov reaction of the carbamimidic chloride "10# with trimethyl phos!phite "Equation "30## ð51BEP501114Ł\ and the amidinoarsine "13^ R0�C5H00\ Ph\ R1�C5H00\ R2�H\Et#\ formed from the attack of alkali metal organoarsides on N\N?!dialkylcarbodiimides "12^R0�C5H00\ Ph# "Equation "31## followed by hydrolysis or alkylation of the intermediate "lithio!amidino#arsines ð57JOM"02#252Ł[

RN

N

Cl

P(OMe)3

Bun

CO2EtRN

N

P

Bun

CO2Et

MeOOMe

O (41)

(21) (22)

R1N

NR1R3

AsR22

(23) (24)

N • N

R1

R1

(42)

i, LiAsR22

ii, H2O or EtBr

5[10[0[1[1 N!Arylimino derivatives with one P function

"i# Amidinophosphonates

Amidinophosphonates "16# have been obtained by three di}erent methods "Scheme 15#[ The _rstmethod involves the reversible reaction of N\N?!diphenylcarbodiimide "14# with the phosphitetriester "15# to give the amidinophosphonates "16^ Ar�Ph\ R0�Me\ Et\ Bu\ Pri\ R1�Ph\R2�TMS# ð89ZOB667Ł[ The second method is the direct aminolysis of imino chlorides "17#\ whichhas been used to give a wide range of amidinophosphonates "16^ Ar�Ph\ 3!ClC5H3\ 2!MeC5H3\3\1!Cl"Me#C5H2\ R0�Me\ Et\ Pri\ R1�H\ R2�Me\ Et\ Pr\ Pri\ Bu\ But\ C5H02\ C5H00 orR1�R2�Me\ Et\ Pr\ Pri# ð66GEP1436401Ł[ The third method yields the amidinophosphonates "16^Ar�Ph\ R0�Me\ R1�Ph\ R2�COP"O#"OMe#1# via an exothermic MichaelisÐArbuzov reactionof trialkyl phosphites and the amidino chlorides "18# ð51BEP501114Ł[

ArN

Cl

P(OR1)2

O

ArN

NR2R3

P(OR1)2

(25) (27)

N • N

Ar

Ar

TMS-OP(OR1)2

(26)

O

PhN

N

Cl

Ph O

Cl

(28)

(29)

(MeO)3P, 100 °C

98%

HNR2R3

10–96%

Scheme 26

"ii# Alkylideneamidophosphonates

In a variant of the trialkyl phosphite and carbodiimide reaction\ treatment of triethyl phosphitewith the chloroalkylcarbodiimide "29# gives the alkylideneamidophosphonate "20# "Equation "32##ð67ZOB0314Ł[


(30)

N • N

Ph

Ph

F3C Cl

P(OEt)3 PhN

N

P(OEt)2

O

Ph

CF3

(31)

(43)

"iii# Amidinophosphines

Phosphines which contain P0H or P0Si bonds will add across the C1N bond of carbodiimideswith transfer of hydrogen or silicon from phosphorus to nitrogen "Scheme 16#^ thus\ the reaction ofN\N?!diphenylcarbodiimide "21# with monophenylphosphine gives the bis"amidino#phosphine "22#^with diphenylphosphine "23^ R0�R1�Ph\ R2�H# the product is the mono"amidino#phosphine "24^R0�R1�Ph\ R2�H#^ and with tris"TMS#phosphine "23^ R0�R1�R2�TMS# it is the trisilylatedamidinophosphine "24^ R0�R1�R2�TMS# ð71IZV0315Ł[ Treatment of compound "24^ R0�H\TMS\ R1�R2�TMS# with methanol gives the desilylated product "26#[ Reaction of compound"24^ R0�R1�R2�TMS# with N\N?!diphenylcarbodiimide or reaction of excess compound "21#with tris"TMS#phosphine gives the product "25# ð70SRI168Ł[ Silicon appears to be transferred inpreference to hydrogen because the reaction of bis"TMS#phosphine "23^ R0�H\ R1�R2�TMS#gives the product "24^ R0�H\ R1�R2�TMS#[

(32)

N • N

Ph

Ph

PhPH2NPh

PhP

PhHN

PhHN

NPh

PhN

N(Ph)R3

PR1R2

(33)

PhN

P

N(Ph)TMS

N(Ph)TMS

N(Ph)TMS

(36)

PhN

NHPh

PH2

(37)

(35)

R1 PR2

R3

(34)

MeOHR1 = H, TMSR2 = R3 = TMS

N • NPh

PhR1 = R2 = R3 = TMS

Scheme 27

5[10[0[1[2 N!Acylimino derivatives with one P function

N!Acylimino derivatives are obtained from dichloromethyl isocyanate precursors[ The reactionof "dichlorophosphinyl#dichloromethyl isocyanate "27# with an alcohol ROH "R�Me\ Et# in thecold gives the chloroimine "28^ R�Me\ Et# which on treatment with diethylamine gives the N!acylimino compound "39^ R�Me\ Et# "Scheme 17# ð60ZOB1044Ł[ Similarly\ the N!phos!phinylcarbonylimino derivative "31\ R�Me\ Et# is obtained by treating the isocyanate "30^ R�Me\Et# with triethylphosphite "Equation "33## ð62ZOR0704Ł[

P

O

Cl

Cl

Cl

OCN

Cl RO N POR

O Cl

OOR

RO N POR

O NEt

OOR

ROH, NEt3 Et2NH

(38) (39) (40)

Scheme 28


OCN

NR2

Cl

ClP(OEt)3

50% P N POEt

O NR2

OOEt

EtO

OEtO

(41) (42)

(44)

5[10[0[1[3 Hydrazono derivatives with one P function

Hydrazono derivatives are obtained by several di}erent reactions] the reaction of chloro!hydrazones with nitrogen nucleophiles^ the 0\2!addition reaction of amines and nitrile amines^ thetreatment of diazonium salts with a!phosphineacetyl derivatives^ alkylation reactions^ and oxidationreactions[

N?!Aryl!C!"dialkoxyphosphoryl#formamidrazones "33^ X�NR11\ Ar�3!NO1C5H3\ 3!HalC5H3\

3!MeC5H3\ Hal�F\ Cl\ Br\ I\ R0�OMe\ OEt\ OPri\ R1�Me\ Ph# are prepared in a yield of 18Ð88) by the treatment of chlorohydrazono derivatives "32# with aqueous solutions of amines"Equation "34## ð89ZOB0182\ 89ZOB1583Ł[ Phosphonic acid diamides "33^ X�NMe1\ Ar�3!NO1C5H3\R0�NEt1# are prepared in a similar fashion ð89ZOB0875Ł\ whilst treating compound "32^ Ar�3!NO1C5H3\ R0�OPri# with sodium azide or sodium nitrite gives the azido! and nitrohydrazones "33^X�N2\ NO1\ Ar�3!NO1C5H3\ R0�OPri# ð89ZOB0879Ł[

(45)ArHNN P

R1

X

OR1

(44)

ArHNN P

R1

Cl

OR1

(43)

R22NH or

NaN3 or

NaNO2 orR3NHNH2

N?!Phosphineformamidrazone "35# is obtained by the 0\2!addition of diisopropylamine to thenitrile imine "34# "Equation "35## ð80CB0628Ł[ Related 0\2!additions of monoalkylamines to nitrileimines have been reported ð81CC0163Ł[

(45) (46)

P N

CF3

F3C

F3C

N

P

NPri2

NPri2

S

+

– P N

CF3

F3C

F3C

H

N

P

NPri2

NPri2

NPri2

S

(46)Pri

2NH

54%

An interesting solvent e}ect is observed in the preparation of "arylhydrazono#"arylazomethyl#phosphonates "49^ Ar�Ph\ 3!MeOC5H3\ 3!NO1C5H3\ 3!ClC5H3\ 3!BrC5H3\ 3!IC5H3\ R�Me\ Et\Pri#[ The reaction of the phosphinylaldehyde "36# with diazonium salts "37^ X�Cl\ BF3# gives thephosphonate "49# as the major product in pyridine\ and compound "38# as the major product inwater "Equation "36## ð75ZOB0316\ 76ZOB1356Ł[ Phosphonate "49^ Ar�3!NO1C5H3\ R�Pri# has alsobeen prepared by the reaction of compound "32^ Ar�3!NO1C5H3\ R0�Pri# with 3!nitrophenyl!hydrazine "Equation "34#^ R2�3!NO1C5H3# ð89ZOB0177Ł[ The coupling reaction of the phos!phineacetic acid salt "40# with 1 molar equivalents of diazonium salt "41# gives thebis"arylazo#methylenephosphine "42#\ which is isolated as the tetra~uoroborate salt "43^ Ar�Ph\3!NO1C5H3\ 3!Me1NC5H3\ 1!MeOC5H3# "Scheme 18# ð51ZN"B#671Ł[

P

O

OR

OR

OHC

+ ArN2+ X–

ArHNN

CHO

P

OR

O

RO

ArHNN

N

P

OR

O

RO

NAr

(47) (48) (49) (50)

(47)+


+ ArN2+

–CO2

71–90%N

N

PPh3

(51) (52) (53)

HO2C PPh3 Cl–+

ArN NAr

N

N

PPh3

(54)

ArHN NAr

BF4–

+

HBF4

Scheme 29

Other preparations of compounds in this class include the isolation of the inner salt "45# from thealkylation of the formamidrazone "44# with methyl iodide "Equation "37## ð80ZOB665Ł\ and oxidationof the amidrazone "46^ R�But# with silver"I# oxide to give the N!"arylazo#"dialkoxyphos!phoryl#methylene!t!butylamine "47^ R�But# "Equation "38## ð82S48Ł[ The "arylazo#imines "47#cannot be made with an N2!methylene group "e[g[\ R�Me\ PhCH1# because the products of suchreactions tautomerise to give N!alkylideneamide arylhydrazones which then cyclise to form dihydro!0\1\3!triazoles[

N

N

H

P

NMe2

OPri

O

PriO

N

N

H

P

NMe2

O–

O

PriOMe

+

(55) (56)

MeI

60%(48)

N

P

RHN

OPri

O

(57) (58)

Ag2O

70%(49)

NH

NO2

PriO

N

P

RN

OPri

O

N

NO2

PriO

5[10[0[1[4 Diazonium derivatives with one P function

The diazonitromethyl derivatives "59^ R0�Ph\ R1�OMe^ R0�R1�Ph\ OMe\ OEt# and thenitrate side products "50# are obtained by treating the diazomethylphosphonates "48# with dinitrogenpentoxide "Equation "49## ð68LA0991Ł[

N2

PO

R2

R1

(59)

N2

PO

R2

R1

(60)

NO2

PO

R2

R1

(61)

ONO2N2O5, –20 °C

+ (50)

5[10[0[1[5 N\N!Dialkyliminium derivatives with one P function

1!Phosphaallylic salts and phosphorylated amidinium salts may be prepared from chloro!amidinium salts or phosphaalkenes[

1!Phosphaallylic salt "57^ R1�Me\ X�Cl# is formed in high yield by the reaction oftris"TMS#phosphane with two molar equivalents of the imidoyl chloride "55^ R1�Me# "Scheme 29#ð72AG"E#434\ 73AG"E#892Ł[ The analogous compound "57^ R1�Et\ X�CF2SO2#\ along with otherunidenti_ed products\ is formed by rearrangement of the 0\2!tetraalkylformamidinium!substitutedcyclotetraphosphane "56# produced by cyclisation of the cationic diphosphene "53^ R0

1N�Pri1N\

1\1\5\5!tetramethylpiperidinyl^ R1�Et^ X�CF2SO2#[ Diphosphene cation "53# is obtained by thereaction of the chlorophosphine "52# with TMS trifylate or by the condensation of phosphaalkene"51# with chlorophosphenium cation\ followed by valence isomerism of the _rst!formed phos!phaalkeneÐphosphenium cation "54# ð80TL1664Ł[ The 1!phosphaallylic salt "57^ R1�Me\ Et\ X�Cl#


is also prepared by leaving benzene solutions of the phosphaalkene "52# standing at room tem!perature for several hours[

P

P P

PNR1

2

R12N

NR22

R22N

NR22

R22N

(62)

+

X–

(63)

(64)

+ X–

(65)

+Cl–

R22N

NR22

P

NR22

+

+

(66)

+

X–NR22

(67) (68)

R22N

NR22

P P

NR12

R22N

NR22

P P

NR12

R22N

NR22

Cl

R22N

NR22

P TMS

R22N

NR22

P P

NR12

Cl

ClP+NR12 CF3SO3

– CF3SO3-TMS

22 °CP(TMS)3

MeCN80–96%

PhMe, 22 °C

Scheme 30

2

2 X–

The synthesis of phosphorylated amidinium salts is shown in Scheme 20[ Reaction of the cation"60^ R1�Me# with triethyl phosphite gives the phosphonic anhydride inner salt "62^ R1�Me#ð61JOC1629Ł via the monophosphorylated amidinium salt intermediate "58^ R1�Me# which canalso\ depending upon reaction conditions\ give the betaine "69^ R1�Me# as the major productð61JCS"D#1156\ 67JPR278Ł[ The reaction of the cation "60^ R1�Me# with an excess of diethyl phenyl!phosphonite gives the salt "65^ R1�Me#\ which is converted to the stable inner salt "61^ R1�Me#by gentle warming ð61JOC1629Ł[ In contrast\ ethyl and isopropyl diphenylphosphinite "63^ R2�Et\Pri# have only one displaceable alkyl group and undergo a standard MichaelisÐArbuzov reactionwith cation "60# to give the salt "64^ R1�Me# ð61JOC1629\ 67JPR278Ł[ The inner salt "61^ R1�Me# isalso prepared by oxidation of the electron!rich phosphaalkene "66^ R1�Me# with ozoneð75AG"E#346Ł[

5[10[0[2 Iminocarbonyl Derivatives with One Nitrogen and One Metalloid Function

This class of compounds consists largely of boron!containing compounds[ There appear to be nogermanium!containing compounds and only one example of a silanecarboximidamide[

5[10[0[2[0 Silicon derivatives

Silanecarboximidamide "68# is prepared from the reaction of N\N?!diphenylcarbodiimide "21# andbis"TMS#mercury "67# "Equation "40## ð61JOM"31#182Ł[


R22N

NR22

P

OEt

OEt

O

R22N

NR22

P

OEt

O–

O

R22N

NR22

Cl

R22N

NR22

P

Ph

O–

O

R22N

NR22

P O

P

NR22

NR22–O

O –OO

R22N

NR22

P

+

Ph

Ph

O

+

–EtCl

Cl–+

R22N

NR22

P

(70)

(69)

+

Ph

OEt

O

(70)

(72)

+

(71)

+

(73)

+ +

(75) (76) (77)

Cl–

P

NR22

R22N

Ph2POR3

(74) PhP(OEt)2

Ph

2 O3

–2 O2

P(OEt)3

–EtCl

Scheme 31

N • N

Ph

Ph

Hg(TMS)2 (78)PhN

N(Ph)TMS

TMS(32) (79)

(51)

5[10[0[2[1 Boron derivatives

Borane carboximidamides "71# are crystalline compounds which are stabilised by internal donorÐacceptor bonding ð71IZV1269Ł[ Compounds "71^ R0�Ph\ R1�R2�Me\ Pri\ R3�Bu\ Pri^ R0�Me\R1�R2�Ph\ R3�Bu# ð68DOK"134#010Ł and "71^ R0�Ph\ R1�R3�Pri\ R2�H# ð71IZV1269Ł areprepared by the exothermic reaction of phenyl isocyanide with either a dialkylboryl derivative "70#or a boraneamidine "72^ R1�Pri#\ respectively "Scheme 21#[ The mechanism of the latter reactionmay involve the intermediate "73#\ which undergoes an electrocyclic reaction[ The sterically hinderedboraneamidine "72^ R1�But# gives the related product "71^ R0�Ph\ R1�H\ R2�But\ R3�Pri#via the insertion of phenylisonitrile into the nitrogenÐboron bond of the compound "72# instead ofan electrocyclic reaction ð71IZV1269Ł[ The reaction of the 1!"dialkylboryl#aminopyridine "74# withphenyl isocyanide gives the product "75# by the electrocyclic and not the insertion mechanism"Equation "41## ð76IZV0028Ł[

N NH

BBu2 PhN

PhNC

87%

(85)

B N

N

BuBu

(86)

H

(52)+

–

The only examples of N?!alkylboranecarboximidamides reported in the literature are car!boximidamides "76^ R0�But\ R1�NMe1^ R0�Pri\ R1�Me# formed in very low yields as sideproducts of other reactions ð79ZAAC"375#88\ 71JOM"120#080Ł[


R2N

R1

NHR3

R43B or

R42BSalk

NB

N

R1

R2 R3

R4 R4

+

–

(80) (81)

(84)

PhNC

77–89%

N

BNH

R2 Ph

Pri Pri

–PhN

(82)

N

BN

R2 R1

R4 R4

–PhN R3+

+R2HN

Ph

N

Pri2B

(83)

i, PhNC

ii, [1,3]-H shift

Scheme 32

(87)

R1N

NMe2

BR22

5[10[0[3 Iminocarbonyl Derivatives with One Nitrogen and One Metal Function

Most of the compounds in this section are carbene complexes of Group 07 transition metalsthat are formed by nucleophilic reactions of amines with isocyanide ligands of transition!metalcomplexes[

5[10[0[3[0 Group 07 transition!metal derivatives

Azetidine reacts with the coordinated isocyanide ligand of the neutral complex "cis!77^ M�Pd\Pt\ R�But\ 3!MeOC5H3# and the cationic complex "trans!89^ M�Pd\ Pt# in THF to form thecorresponding diaminocarbene derivatives "78 and 80# "Equations "42# and "43## ð89JCS"D#0086Ł[Azetidine also reacts with the bis"isocyanide# complexes "cis!81^ R�But\ 3!MeOC5H3#\ convertingone or two ligands into acyclic carbenes "82^ R�But and 83^ R�3!MeOC5H3# "Equation "44##[The isocyanide complexes "cis!84^ M�Pd\ Pt# react in THF with two equivs of azetidine to a}ordthe cationic acyclic diaminocarbene complexes "85# containing a metal!coordinated azetidine ligand"Equation "45## ð89JCS"D#0086Ł[ Hydrido alkyl carbene complexes "87^ R�CH1CN\ CH1CF2# areprepared by reaction of azetidine with hydrido alkyl isocyanide complexes "86# "Scheme 22#[ Theselatter complexes react with triphenylphosphine with elimination of HR to give the complex "trans!88# by a nonreductive elimination pathway ð89OM0338Ł[

cis R N C M(PPh3)Cl2

NH

N

NHR

M(PPh3)Cl2(88) (89)

(53)cis-

(54)N C M(PPh3)Cl

NH

N

N

M(PPh3)2Cl

(90) (91)

MeOtrans-

H

OMeBF4

–BF4

–

++

trans-


(55)

NH

N

NHR

Pd(NCR)Cl2(93)

cis-

cis-(RCN)2PdCl2(92)

R = But

R = 4-MeOC6H4

RHN

N PdCl2

2

(94)

trans-

cis-R N C M(PPhMe2)Cl2

NH

2

RHN

N M

Cl

N

PPhMe2

H (56)

+

Cl–

(96)(95)

N C Pt

NH

NH

N Pt

Ph3P

R

H

(98)(97)

MeO

R

PPh3

H

MeO

PPh3

–HRN

N Pt

Ph3P

PPh3

H

(99)MeO

Scheme 33

Dimethylamine and diethylamine have been used in place of azetidine in reactions with thetetrakis"t!butyl isocyanide#rhodium"I# salt "099# to give crystalline 0 ] 0 adducts "090^ R�Me\ Et#containing a s!bonded amidinium cation "Equation "46## ð61JCS"D#0292Ł[

[(ButN≡C)4Rh]+ BF4–

R2NHRh(C≡NBut)3 BF4

–

ButHN

R2N

(100) (101)

(57)

+

5[10[0[3[1 Other metal derivatives

The few examples of non group 07 transition metal derivatives include the trialkylstannyl!and trialkylplumbylformamidines "093^ M�Sn\ Ar�3!MeC5H3\ R0�R1�Me^ M�Pb\ Ar�Ph\R0�Bu\ R1�Et# obtained by the 0\0!addition of a metal amide "091# to an aryl isocyanide "092#"Equation "47## ð55TL2312\ 57JOM"03#216Ł and the bis"diazonitromethyl#mercury "095# prepared bythe reaction of nitrodiazomethane "094# with mercury"II# oxide "Equation "48## ð60LA"642#032Ł[

(58)R13MNR2

2 + ArNC ArN

MR13

NR22

(103) (104)(102)

N2

NO2 + HgON2

Hg

N2

NO2

NO2

(59)

(105) (106)

554At Least One P\ As\ Sb or Bi

5[10[1 IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE P\ As\ Sb OR BiFUNCTION "AND NO HALOGEN\ CHALCOGEN OR NITROGEN FUNCTIONS#

5[10[1[0 Iminocarbonyl Derivatives with One P\ As\ Sb or Bi Function and One P\ As\ Sb or BiFunction

Although a number of iminocarbonyl derivatives containing two phosphorus functions exist\there are no examples where the _rst function is phosphorus and the second function is arsenic\antimony or bismuth[ Iminocarbonyl derivatives in which the _rst function is arsenic\ antimony orbismuth are known only for organometallic diazomethanes[

5[10[1[0[0 Iminocarbonyl derivatives with one P function and one P\ As\ Sb or Bi function

"i# Bis"phosphino#iminocarbonyl derivatives

Low!coordination phosphorus compounds such as the methylenephosphines "R�\S�!096# and"R�\R�!097# in which the carbon atom of the iminocarbonyl group is connected to two 2!valentphosphorus atoms\ are relatively unstable and have been studied very little ð71AG"E#337Ł[ However\"diazomethylene#bis"phosphonous diamides# "000^ R�Pri# are more stable and are formed in goodyield by the addition of the chlorophosphane "009^ R�Pri# to the lithium salt of the "bisphos!phanyl#diazomethane "098^ R�Pri# "Equation "59## ð75JA6757\ 77JA1552\ 78JOM"261#190\ 89JA5166Ł[Minor modi_cation to one of the reagents dramatically alters the course of the reaction\ andtreatment of compound "098^ R�C5H00# with compound "009^ R�C5H00# gives a mixture of thediazo derivative "000^ R�C5H00# and the nitrile imine "001^ R�C5H00# in a 3 ] 10 ratio ð81JA5948Ł[

N

P

P

Cl

TMS

Ph

Ph

TMS

(107)

N

P

P

Cl

TMS

Ph

Ph

TMS

(108)

N2

P(NR2)2

Li+ ClP(NR2)2

(109) (110) (111) (112)

N2

P(NR2)2

P(NR2)2

–78 °C+ N N

P(NR2)2

(R2N)2P

+–(60)

"ii# Bis"phosphinyl#iminocarbonyl derivatives

The long list of compounds containing 4!valent phosphorus atoms includes diphenyl!\ dialkoxy!\diamino!\ alkoxyamino! and alkoxy~uorophosphinyl derivatives\ and phosphinothioyl derivatives[The methods of synthesis of all these compounds are essentially the same[

"a# Bis"phosphinyl#iminocarbonyl derivatives from carbonimidic dichlorides and or`anophosphorusrea`ents[ The reaction of carbonimidic dichlorides and organophosphorus compounds is the mostpopular method of synthesis of bis"phosphinyl#iminocarbonyl derivatives[ Gross et al[ have prepareda large number of "arylcarbonimidoyl#bisphosphonic acid esters by the reaction of a carbonimidicdichloride with "EtO#1P"O#R "Equation "50#^ R�OEt ð61EGP82655Ł^ R�Me or Et ð61JPR76Ł[ N!"Bis"diphenylphosphinyl#methylene#arylamines are produced in a similar fashion with Ph1P"O#"OR#"Equation "51#^ R�Me\ Et# ð61EGP82655\ 61JPR76Ł[

(61)ArN

Cl

Cl+ (EtO)2P(O)R ArN

P(O)(OEt)2

P(O)(OEt)2


(62)ArN

Cl

Cl

+ 2 Ph2P(O)OMe ArN

P(O)Ph2

P(O)Ph275–84%

The MichaelisÐArbuzov reaction of trichloromethyl isocyanate "002# with alkyldihalo!\ dial!kylhalo! and trialkyl phosphites has been studied extensively by Shokol et al[ "Scheme 23#[ Treatmentof trichloromethyl isocyanate with two molar equivs of ClP"OEt#1 in the presence of FeCl2 ascatalyst gives an intermediate "003# which can be reacted with a variety of nucleophiles^ for example\ethanol gives the carbamate "005^ R�OEt# ð64ZOB0854Ł[ In a similar fashion\ reaction of trichloro!methyl isocyanate with two molar equivs of "EtO#2P gives a related intermediate "004# which canbe converted to either the ester "005^ R�EtO# or urea "005^ R�PhNH# by reaction with ethanolor aniline\ respectively ð62ZOB433Ł[ Phenylsulfonylimino derivatives "008^ R�Me\ Et# are alsoprepared by the MichaelisÐArbuzov reaction "Equation "52## ð55CB0141Ł[

OCN CCl32 ClP(OEt)2, FeCl3 (cat.)

(113) (114)

(115) (116)

OCN

P(O)(OEt)Cl

P(O)(OEt)Cl

Cl

2 P(OEt)3 EtOH

EtOH or PhNH2OCN

P(O)(OEt)2

P(O)(OEt)2

Cl N

P(O)(OEt)2

P(O)(OEt)2

O

R

Scheme 34

PhSO2N

Cl

Cl+ (RO)3P

60 °C

>90%PhSO2N

P(O)(OR)2

P(O)(OR)2

(117) (118) (119)

(63)

"b# Bis"phosphinyl#iminocarbonyl derivatives from carbonimidic dichlorides by metalÐhalo`enexchan`e[ N!"Bis"diphenylphosphinyl#methylene#arylamines are produced from carbonimidicdichlorides by metalÐhalogen exchange with Me1TlP"O#Ph1 "Equation "53## ð62ZC081Ł[

ArN

P(O)Ph2

P(O)Ph2

ArN

Cl

Cl+ 2 Ph2P(O)TlMe2

43–88%(64)

"c# Bis"phosphinyl#iminocarbonyl derivatives from tosyl azides[ "Diazomethylene#bisphos!phonates are synthesised by reaction of tosyl azide with the corresponding C0H active methyleneprecursor in the presence of potassium t!butoxide "Equation "54#^ X�O\ R�OMe\ OEt#ð57CB2623\ 57TL2060\ 81JOC067Ł[ The yield in the reaction is improved by using 1!naphthalene!sulfonyl azide in place of tosyl azide and by separating the silica!sensitive product from theinsoluble sulfonamide by!product by _ltration rather than chromatography ð80S394Ł[ Bis"diphenyl!phosphinothioyl#imino derivatives are made by an analogous reaction "Equation "54#^ X�S\R�Ph# ð64MI 510!91\ 64OMS"09#0910\ 68T070Ł[ Mixed diesters of "diazomethylene#bisphosphonates"010# are obtained in excellent yield by treating the potassium salt of the methylenebisphosphonate"019# with tosyl azide in THF "Scheme 24# ð61S240\ 66JA0156\ 71JOC0173Ł[ The methyl ester group of"010# is hydrolysed with careful temperature control to the phosphonate salt "011# via a trans!esteri_cation reaction with TMS!Br ð71JOC0173Ł[ The a!diazophosphonate intermediate "012# maybe isolated by extraction from CCl3 solution into aqueous base or bu}er followed by evaporation[A study of the stability and photochemical behaviour of a!diazophosphonates has been carried outby Bartlett et al[ ð71CC425\ 71JOC0173Ł[


N2

P(X)R2

P(X)R2

base(65)

P(X)R2

P(X)R2

TsN3 +

N2

P(O)(OPri)2

P(O)(OMe)2

(121)

P(O)(OPri)2

P(O)(OMe)2

(120)

KH, TsN3

78%

TMS-Br

N2

P(O)(OPri)2

P(O)(O-TMS)2

(123)

i, K3PO4

ii, NaOHN2

P(O)(OPri)2

P(O)(ONa)2

(122)

Scheme 35

"d# Bis"phosphinyl#iminocarbonyl derivatives from diazometallic salts[ a!Diazophosphonothioicdiamides are made from diazolithium salts "Scheme 25#[ Addition of chlorophosphane derivatives"014^ R0�Ph\ NMe1# to the lithium salt of the thioxophosphoranyldiazomethane "013^ R1�NPri

1#leads to the diazo compounds "015^ R0�Ph\ NMe1\ R1�NPri

1#[ In contrast\ the chlorophosphanes"014^ R0�But\ NPri

1# react with compound "013^ R1�NPri1# to give the stable nitrile imines "016^

R0�But\ NPri1\ R1�NPri

1#[ In the same way\ chlorophosphane "014^ R0�NPri1# also reacts with

compound "013^ R1�But# to give the nitrile imine "016^ R0�NPri1\ R1�But#[ Nitrile imine "016^

R0�R1�NPri1# rearranges on heating into the isomeric diazo derivatives "015^ R0�R1�NPri

1#[Reaction of the diazo compounds "015^ R0�Ph\ NMe1\ R1�NPri

1# with elemental sulfur givesthe bis"thioxophosphoranyl#diazo derivatives "017^ R0�Ph\ NMe1\ R1�NPri

1# ð89JA5166Ł[ Thechemistry of phosphinothioyl derivatives "015^ R0�R1�NPri

1^ R0�NPri1\ R1�But^ and R0�Ph\

NMe1\ R1�NPri1# has been described by Bertrand and co!workers ð77AG"E#0249\ 77JA1552\ 89JA5166\

80CB0628Ł[

N2

P(S)R22

Li

R12PCl (125), –78 °C

(124)

N2

P(S)R22

PR12

(126)

R12PCl (125)–78 °C85%

N N

PR12

R22(S)P

–+

(127)

55 °CS8

N2

P(S)R22

P(S)R12

(128)

Scheme 36

The diazosilver derivative "018# reacts with the chlorophosphine "029# to give the unstable"bis"TMS#methylene#phosphino#diazomethylphosphine oxide "020#\ which undergoes an immedi!ate 0\4!cyclisation and a TMS shift at low temperature to give the phosphadiazole "021# "Scheme26# ð78S400Ł[

ClP

TMS

TMS

(130)

N2

P(O)Ph2

Ag

(129)

+–78 °C N2

P(O)Ph2

P

TMS

TMS

(131) (132)

P

NN

TMS

P(O)Ph2

TMS

Scheme 37


"e# Bis"phosphinyl#iminocarbonyl derivatives from arylisocyanates[ The only known example ofa P\P?!"carbonimidoyl#bis"phosphonic diamide# is prepared from the reaction of a phosphorus"III#acid anhydride with an aryl isocyanate "Equation "55## ð71ZOB1076Ł[

(Et2N)2PO

P(NEt2)2 + PhNCO PhN

P(O)(NEt2)2

P(O)(NEt2)2

(66)

5[10[1[0[1 Iminocarbonyl derivatives with one As\ Sb or Bi function and another As\ Sb or Bi function

The only representatives of this class of compound are the bis"2!valent# organometallicdiazomethanes "024^ M�As\ Sb\ Bi# prepared by treating arsino!\ stibino! and bismuthino dimethyl!amides "023^ M�As\ Sb\ Bi# with diazomethane "022# "Equation "56## ð64JOM"82#228Ł[ Mixedorganometallic derivatives arise from two step reactions ð66JOM"021#248Ł[

(67)+ Me2MNMe2 N2

MMe2

MMe2

N2

H

H(133) (134) (135)

5[10[1[1 Iminocarbonyl Derivatives with One P\ As\ Sb or Bi Function and One Si\ Ge\ or B Function

5[10[1[1[0 Iminocarbonyl derivatives with one P function and one Si\ Ge or B function

"i# Silicon derivatives

All of the compounds in this class are phosphorus!containing silyldiazomethane derivatives[They are often prepared by the reaction of the lithium salt of a diazomethane derivative witha stoichiometric amount of the requisite chlorophosphane or chlorosilane "Scheme 27#[ Thus\dialkylphosphanylsilyldiazomethanes "026^ X�lone pair\ R0R1R2Si�TMS\ R3�R4�But#ð89JA5166Ł and dialkylaminophosphanylsilyldiazomethanes "026^ X�lone pair\ R0R1R2Si�TMS\R3�R4�dialkylamino# ð81BSF256Ł are prepared readily from chlorophosphanes "025# at lowtemperature^ however\ the phosphavinyldiazoalkanes "026^ X�lone pair\ R0R1R2Si�TMS\R3R4�]C"TMS#1\ ]C"TMS#Ph# are only stable at −67>C and on warming undergo rearrangementreactions to give phosphadiazoles ð78S400Ł[ Silylated a!diazo phosphonates "026^ X�O\R0R1R2Si�TMS\ TBDMS\ SiPri

2\ R3�R4�OMe\ OEt# ð68LA0991\ 74JOM"189#22Ł and phos!phonothioic diamides "026^ X�S\ R0R1R2Si�TMS\ SiPh2\ R3�R4�NPri

1# ð77JA1552\ 80JOC0790Łare prepared from lithiated a!diazo phosphonates "027# by reaction with silyl electrophiles "Z�Cl\CF2SO2#[ The phosphonothioic diamides are formed via nitrile imine intermediates"R0R1R2SiN1N¦

1C−P"S#NPri1#\ which are the only products isolated in reactions with bulky

electrophiles\ "e[g[\ Pri2SiCl#[

N2

P(X)R4R5

SiR1R2R3

N2

Li

SiR1R2R3

(136) (137)

ClP(X)R4R5, –78 °C

X = lone pair

R1R2R3SiZN2

P(X)R4R5

Li(138)

Scheme 38

Dialkylaminophosphanylsilyldiazomethanes "026^ X�lone pair\ R0R1R2Si�TMS\ R3�R4�dialkylamino# are precursors of donor!substituted {stabilised| carbenes ð80AG"E#563\ 80NJC282\81BSF256Ł[ The diisopropylamino analogue "028# on ~ash thermolysis gives the stable phos!phanylcarbene "039# "Scheme 28#\ which undergoes a ð1¦2Ł cycloaddition followed by a ring!opening reaction with either N1O to give the diazo phosphonic diamide "031^ X�O# in a yield of


59) ð80NJC282Ł or TMS!N2 at −67>C to 3>C to form the diazo compound "031^ X�TMS!N#ð80AG"E#563Ł[ The reaction with N1O may be considered a formal oxidation of compound "028#[

N2

P(NPri2)2

TMS

(139) (141) (142)

heat

80%

(Pri2N)2P

TMS

:

(140)

N2O or TMS-N3

N

NZ

P

TMS

Pri2N

Pri2N N2

P(X)(NPri2)2

TMS

Scheme 39

a!Diazo phosphine sul_des "e[g[\ 033^ R�But# ð89JA5166Ł and a!diazo phosphonothioic diamides"e[g[\ 033^ R�NPri

1# ð78JOC3315Ł may be prepared by direct sulfuration of the phosphanyl pre!cursors "032# "Equation "57##[

N2

PR2

TMS

(143)

S8, 22 °C

65–85%N2

P(S)R2

TMS

(144)

(68)

"ii# Germanium derivatives

There are few reports of germanium derivatives\ but preparations involving the use of tri!alkylgermanium chloride are known[ Thus\ the a!diazo phosphonothioic diamide triethylgermaniumderivative "034# is prepared by the same method as the silicon analogue "031# ð77JA1552Ł[ A reactionwhich exploits the weakness of the Ge0P bond of germylphosphines involves an insertion reactionof phenyl isocyanide "Equation "58## ð61JOM"23#72Ł[

N2

P(S)(NPri2)2

GeEt3

(145)

Et3GePEt2Ph NC PhN

PEt2

GeEt3

(69)

"iii# Boron derivatives

The only examples of this class are the internal salts "037^ R�H\ F#[ These are synthesised byoxidative ylidation of the a!diazophosphane "035# with CCl3 followed by reaction with boron!containing Lewis acids "Scheme 39# ð80AG"E#0043\ 81BSF256Ł[

N2

P(NPri2)2

TMS

(146)

CCl4N2

P(NPri2)2

BR3

(148)

Cl+

–

BR3

>80%N2 •

(147)

P(NPri2)2

Scheme 40

Cl

5[10[1[1[1 Iminocarbonyl derivatives with one As\ Sb or Bi function and one Si\ Ge or B function

"a!Diazo"TMS#methyl#dimethyl arsines\ stibines and bismuthines "049^ M0�Si\ M1�As\ Sb\ Bi\R�Me\ n�2# are prepared by the reaction of "TMS#diazomethanes "038# with metal amides


"Equation "69##[ Trimethyltin chloride is used as a catalyst for the arsine derivative ð79JOM"080#260Ł[The "diazotrimethylgermylmethyl#dimethylarsine "049^ M0�Ge\ M1�As\ R�Me\ n�2# is pre!pared in a similar fashion ð66JOM"021#248Ł[

N2

M1Me3

(149)

N2

M1Me3

(150)

M2Me3

Me2NM2Me2, <0 °C(70)

5[10[1[2 Iminocarbonyl Derivatives with One P\ As\ Sb and Bi Function and One Metal Function

The only examples of this class are diazomethane derivatives prepared as intermediates for thestudy of carbenes[ Most of the compounds are prepared by metallation or transmetallation ofdiazomethane precursors[

5[10[1[2[0 Iminocarbonyl derivatives with one P function and one metal function

"i# Group 0 metals

Diazolithium salts "041^ X�lone pair\ R0�R1�NPri1^ X�S\ R0�R1�NPri

1\ But# are preparedat low temperature by treating the corresponding diazomethane precursors "042# with BuLi "Scheme30# ð89JA5166\ 80OM2194Ł[

N2

P(S)(NPri2)2

SnMe3

(151)

N2

P(X)R1R2

Li

(152)

Me3SnCl, –78 °C

95%

N2

P(X)R1R2

(153)

BuLi, –78 °CX = O or lone pair

HgO or Hg(acac)2X = O

Ag2O or Ag(acac)X = O

N2

P(O)R1R2

Hg

(154)

N2

P(O)R1R2

Ag

(155)N2

P(O)R1R2

Scheme 41

"ii# Transition metals

The phosphorus!containing diazomethylsilver "044^ R0�R1�OMe\ OEt^ R0�OMe\ R1�Ph#ð60LA"637#196\ 78MI 510!90Ł and the bis"diazomethyl#mercury "043^ R0�R1�OMe\ OEt\ Ph#ð60JOC0268\ 60LA"637#196Ł are prepared by metallation reactions with metal oxides or metal acetyl!acetonates "Scheme 30#[ The stannyldiazomethane "040# is prepared by transmetallation ofcompound "041^ X�S\ R0�R1�NPri

1# with trimethylstannyl chloride ð81JA5948Ł[ The crystallinebis"diazomethylene#mercury"II# salt "046# is produced by the catalytic decomposition of the


diazomethylenephosphorane "045# with mercury"II# chloride followed by anion exchange withpotassium hexa~uorophosphate "Equation "60## ð81BSF256Ł[

N2

P+Cl(NPri2)2

Hg

(157)

N2

P+Cl(NPri2)2

2 PF6–N2 • PCl(NPri

2)2

i, HgCl2ii, KPF6

90%

(156)

(71)

5[10[1[2[1 Iminocarbonyl derivatives with one As\ Sb and Bi function and one metal function

Diazomethylarsine derivatives with trimethylstannyl and trimethylplumbyl substituents "047^M�Sn\ Pb# are prepared by metallation of diazomethylarsines "048# with metal amides "Scheme31#[ Explosive bis"diazo"dimethylarsino#methyl#mercury "059# is produced using Hg"N"TMS#1#1 asmetallating agent ð66JOM"021#248Ł[

N2

AsMe2

MMe3

N2

AsMe2N2

AsMe2

Hg

AsMe2

N2

Me3SnNMe2 or

Me3PbN(TMS)2

(158) (159) (160)

Hg[N(TMS)2]2

Scheme 42

5[10[2 IMINOCARBONYL DERIVATIVES CONTAINING AT LEAST ONE METALLOIDFUNCTION "AND NO HALOGEN\ CHALCOGEN\ OR GROUP 4 ELEMENTFUNCTIONS#

5[10[2[0 Iminocarbonyl Derivatives with Two Metalloid Functions

5[10[2[0[0 N!Unsubstituted iminocarbonyl derivatives

The electronic structure of HN1C"TMS#1 has been calculated but its synthesis is not reportedð81MI 510!90Ł[

5[10[2[0[1 N!Alkyl! and N!aryliminocarbonyl derivatives

These compounds are prepared by the insertion of alkyl! or aryl isocyanides into metalÐmetalbonds or by transmetallation reactions[

N!Alkylbis"silyl#imines are less stable than their N!aryl analogues and only one N!alkyl!sub!stituted compound has been reported[ The N!cyclohexyl derivative "050^ R�C5H00# is prepared bythe insertion reaction of N!cyclohexyl isocyanide into the Si0Si bond of a disilane with catalysisby Pd"9# ð76TL0182Ł or Pt"9# ð89JAP1198768Ł "Equation "61#\ M�Pd\ Pt#[ Sterically!hindered t!alkylisocyanides fail to undergo the reaction[ A wide range of N!aryl analogues has been prepared by thePd"9#!catalysed method ð76TL0182Ł[ The reaction is exothermic with disilanes containing electron!withdrawing substituents[ A study of the insertion of aryl isocyanides into the Si0Si linkage ofpolysilanes indicates that palladium"II# acetate is a better catalyst for the preparation of poly"sila"N!substituted#imines# ð77JA2581\ 80JA7788Ł[

RNC + (R1R2R3Si)2

M(PPh3) (cat.) NR

R1R2R3Si SiR1R2R3

(161)

(72)


"1\5!Xylylimino#bissilanes "054^ SiR0R1R2�TMS\ t!butyldimethylsilyl"TBDMS## are made from"1\5!xylylimino#"TMS#methyllithium "052# by treatment with the requisite chlorosilane "Scheme 32#ð76JA6777Ł[ ""1\5!Xylylimino#trialkylsilyl#metal derivatives are of interest as acyl anion syntheticequivalents^ the 1\5!xylylimino copper!containing compound "053# is more stable than its 1!toly!limino counterpart[

N

SnMe3

SiR1R2R3

N

Li

SiR1R2R3

N

'Cu'

SiR3

(162) N

TMS

SiR1R2R3

BuLi, –78 °C(164)

(163)

(165)

'Cu'X, THF, –78 °C

TMS-Cl, >70%

Scheme 43

5[10[2[0[2 N!Haloiminocarbonyl derivatives

The electronic structures of the imines HalN1C"TMS#1 have been calculated but their synthesesare not reported ð81MI 510!90Ł[

5[10[2[0[3 N!Aminoiminocarbonyl "diazomethane# derivatives

The major methods of preparation of this class of compounds are transmetallation\ diazo grouptransfer and cycloaddition reactions[

Examples of metallation reactions include the treatment of silylated ð76OM0746Ł and germylatedð69JCS"A#1843Ł lithiodiazomethanes "055^ R0�TMS\ GeMe2# with chlorosilanes and chlorogermanesto give bis"silyl#diazomethanes "056^ R0�TMS\ R1�TMS\ "TMS#SiMe1\ "TMS#2Si# and bis"ger!myl#diazomethanes "056^ R0�R1�GeMe2#\ respectively "Scheme 33#[ Bis"germyl#diazomethane"056^ R0�R1�GeMe2# is much less stable than its silyl counterpart and has also been prepared bya dimethylamine elimination reaction with diazomethane "057# ð69JCS"A#1843Ł[ This method failsfor the less reactive amides of silicon "i[e[\ TMSNMe1# and boron "i[e[\ Ph1BNMe1# owing to theirless ionic character[ A further method of preparation of this class of compound involves the transferof the diazo group from tosyl azide to the carbanion "058^ R0�R1�TMS\ GeMe2# derived frombis"TMS#! or bis"germyl#methanes ð79JA0473Ł[

N2

R1

Li

(166)

N2

R1

R2

(167)

R2Cl

R1, R2 = TMS, Me3Ge

CH2N2

(168)

Me3GeNMe2

R1, R2 = Me3Ge

58%

TsN3

R1 = R2 = TMS, Me3Ge Li

R1

R2

Scheme 44

(169)

A more complex route to bismetallated diazomethanes involves cycloaddition reactions of met!alloethenes "Scheme 34#[ Bis"TMS#diazomethane "062^ R0�R1�TMS# is formed by decompositionof the unstable ð1¦2Ł cycloadduct "060# derived from silaethene "069^ R0�R1�TMS# and N1O


ð77CB0396Ł[ A similar reaction involving the ð1¦2Ł cycloaddition of silaethene "069^ R0�TMS\R1�TMS\ TBDMS# with a silyl azide R2N2 "R2�silyl group# forms siladihydrotriazole "063#\which undergoes a ð1¦2Ł cycloreversion to give the product "062^ R0�TMS\ R1�TMS\ TBDMS#ð75CB0356\ 75CC480\ 76CB0192Ł[ Siladihydrotriazoles also rearrange by an alternative mechanism togive bis"silyl!substituted#diazomethanes and this reaction has been used to prepare a wide range ofsilyl compounds "064^ R0ÐR2�silyl group# ð75CB0356\ 76CB0192\ 76CB0102Ł[ Similar reactions areobserved with the silaoxadiazole "060^ R0�R1�TMS#\ which rearranges to give the bis"silyl!substituted#diazomethane "061^ R0�R1�TMS# ð77CB0396Ł[

Me2Si

R1

R2

N2

R1

R2

N2

SiMe2

R2

– Me2Si N

R3

(170)

N N

Me2Si

OR2

R1

(171)

R1O

N2

SiMe2

R2

R1R3NN N

Me2Si

NR2

R1

R3

(174)

(172)

(173)

(175)

N2O

R3N3, –78 °C >22 °C

–1/n (Me2SiO)n

Scheme 45

The use of the germaethene "066# and the alkylidenaminoborane "068# in reactions analogous tothose shown for silaethene in Scheme 34 produces the respective germylsilyldiazomethanes "065 and067# "Scheme 35# ð75CB1879\ 76CB0192Ł and the boranylsilyldiazomethane "079# "Equation "62##ð78CB484Ł[

N2

GeMe2

TMS

TMS(But)N

Me2Ge

TMS

TMSN2

GeMe2

TMS

TMS-OButN3 N2O

(176) (177) (178)

Scheme 46

N2

BNPri2

TMS

(TMS)2N

(180)

TMS-N3Pri

2NB

TMS

TMS

(179)

(73)

Finally\ diazoalkanes are useful precursors to carbenoid species[ The transformation is catalysedby transition metals\ and an investigation of the reaction of the anion of "TMS#diazomethane withM"CO#4PPh2 "M�Cr\ W# "Scheme 36# resulted in the isolation of two stable crystalline N!bondeddiazoalkaneÐmetal complex intermediates "070^ M�Cr\ W# ð77CC0487Ł[

5[10[2[0[4 N!Silyliminocarbonyl derivatives

N!Silylated bis"TMS#imines "072^ R�TMS\ "TMS#1NSiMe1# are formed as side products in thereaction of silaethene "071# with silyl azides "RN2# "Scheme 37# ð70CB2407\ 76CB0192Ł[


(181)

TMS-Cl

–LiClN2

TMS

Li

M(CO)5PPh3

–CON

M

COOC

PPh3OC

CO

N

Li TMS

N

M

COOC

PPh3OC

CO

N

TMS TMS

Scheme 47

Me2Si

TMS

TMS

RN3

N N

Me2Si

NTMS

TMS

R

–Me2SiN2RN

TMS

TMS

(183)(182)

Scheme 48

5[10[2[1 Iminocarbonyl Derivatives with One Metalloid Function and One Metal Function

The only examples of this class of compound have silicon as the metalloid[

5[10[2[1[0 N!Alkyl! and N!aryliminocarbonyl derivatives

These compounds are similar to iminocarbonyl derivatives with two metalloid functions "Section5[10[2[0[1# and are prepared in a similar fashion by the insertion of alkyl! or aryl isocyanides intometalÐmetal bonds and by transmetallation reactions[

Organosilyl"N!alkylimino#stannanes "075^ R0�R1�Me\ R2�Pri\ C5H00\ C5H02\ 1!MeC5H3^R0�Bu\ R1�Me\ R2�Pri^ R0�Me\ R1�But\ R2�Pri# are produced by the Pd"9#!catalysedinsertion of isonitriles into the Si0Sn bond of organosilylstannanes "Equation "63## ð75CC879Ł[The reaction proceeds in competition with the disproportionation of compound "073# to give thedistannane "076# and disilane "077#[ The Pd"9#!catalysed reaction of "TMS#dimethylstannane withthe sterically bulky ButNC gives only disproportionation products[

R3N

SnR13

SiMe2R2

(186)

R13SnSiMe2R2 + R3NC

Pd(PPh3)4, PhMe

28–71%+ (R1

3Sn)2 + (R2Me2Si)2

(184) (185) (187) (188)

(74)

The lithium derivative "052^ SiR2�TMS\ TBDMS#\ generated in situ at −67>C by trans!metallation of the trialkylstannane "051^ SiR2�TMS\ TBDMS# with BuLi\ has been converted intovarious copper reagents "054^ SiR2�TMS# by reaction with CuBr =SMe1 or Cu acetylide "Scheme 32#ð76JA6777\ 77TL244Ł[ The trialkylstannane "051^ SiR2�TMS\ TBDMS# is prepared by the isonitrileinsertion reaction "Equation "63#^ R0�Me\ R1�Me\ But\ R2�1\5!Me1C5H2# ð76JA6777\ 77JA2581Ł[

An additional method of synthesis involves the deprotonation of carbene complexes of group 05metals "078^ M�Cr\ Mo\ W\ SiR2�Ph2Si\ Ph1MeSi# with strong bases to give carbene complexes"089# containing formal imino bonds "Equation "64## ð89JOM"274#110Ł[

M

CO

OC

CO

CO

OC

EtHN SiR3

(189) (190)

M

CO

OC

CO

CO

OC

EtN SiR3–

Li+base

(75)

5[10[2[1[1 N!Aminoiminocarbonyl "diazomethane# derivatives

These compounds are obtained by metallation reactions[ Lithium silyldiazomethides "080^SiR2�TMS\ tips\ TMS!SiMe1# are obtained by treatment of silyldiazomethanes "081# with BuLi or

564Two Metal Functions

LDA "Scheme 38#[ The reaction is usually carried out at low temperature "−67>C# in THF assolvent ð74H"12#1260\ 80OM2194Ł[ The plumbyl! and stannyl"TMS#diazomethanes "082^ SiR2�TMS\M�Pb\ Sn# are obtained by reaction of "TMS#diazomethane "081# with metal amidesð79JOM"080#260Ł[ The stannyl"triisopropylsilyl#diazomethane "085# is obtained from the reaction ofbis"trimethylstannyl#diazomethane "084# with Pri

2SiCl in a variety of solvents "THF\ CH1Cl1 ortoluene#\ but the same reaction performed in the absence of solvent gives the bis"tri!isopropylsilyl#nitrile imine "083# "Scheme "49##[ A discussion of the scope and mechanism of thesereactions has been provided by Bertrand and co!workers ð81JA5948Ł[

N2

SiR3

Li

BuLi or LDA

(191)

N2

SiR3

(192)

N2

SiR3

MMe3

(193)

Me3MN(TMS)2

>81%

Scheme 49

Scheme 50

N2

SnMe3

(195)

N2

SnMe3

SiPri3

(196)

2 Pri3SiCl

solventSnMe3

N N

SiPri3

Pri3Si

+–

(194)

2 Pri3SiCl

neat

Organic diazoalkanes are useful as precursors to carbenoid species or as 0\2!dipolar cycloadditionreagents in heterocyclic synthesis\ and consequently a number of N!coordinated diazoalkanetransition!metal complexes are known "see\ e[g[\ Scheme 36#[ C!Bonded metal diazoalkanecomplexes are fewer in number but examples include the crystalline "diazomethyl#trimethylsilanenickel"II# complex "088# which decomposes above −14>C[ It is formed by treatmentof lithium "TMS#diazomethide "086# with the nickel reagent "087# in a high!yielding reaction "Scheme40# ð89JA4240Ł[ The unstable "diazomethyl#trimethylsilanerhodium"I# complex "190# is preparedfrom the reagent "199#\ also in high yield\ and on reaction with iodomethane produces the morestable rhodium"III# diazo complex "191# ð76OM0711Ł[

N2

TMS

(199)

LiNi

N2 TMS

Me3P PMe3

Cl

Rh

N2 TMS

(197)

Me3P PMe3

Me3P PMe3Rh

N2 TMS

(201)

Me3P Me

I PMe3

(202)

Cl2Ni(PMe3)2 (198)

100%

Rh(PMe3)4Cl (200)

2 MeI

–Me4PI

PMe3

Scheme 51

5[10[3 IMINOCARBONYL DERIVATIVES CONTAINING TWO METAL FUNCTIONS

There are no examples of this class of compound\ if organometallic complexes with bridgingisocyanide ligands ð71COMC!I"3#412Ł are excluded[


6.22Functions Containing DoublyBonded P, As, Sb, Bi, Si, Ge, Bor a MetalVADIM D. ROMANENKOInstitute of Organic Chemistry, Kiev, Ukraine

and

MICHEL SANCHEZ and LYDIA LAMANDEUniversite Paul Sabatier, Toulouse, France

5[11[0 FUNCTIONS CONTAINING DOUBLY BONDED P\ As\ Sb or Bi 567

5[11[0[0 General Remarks 5675[11[0[1 Dicoordinate Phosphorus and Arsenic Derivatives 567

5[11[0[1[0 Dihalomethylenephosphines\ Hal1C1PY 5675[11[0[1[1 Oxyèn! and sulfur!substituted methylenephosphines\ RO"X#C1PY and RS"X#C1PY 5725[11[0[1[2 Nitroèn! and phosphorus!substituted methylenephosphines\ R1N"X#C1PY

and R1P"X#C1PY 5735[11[0[1[3 Silicon! and èrmanium!substituted methylenephosphines\ R2Si"X#C1PY

and R2Ge"X#C1PY 5775[11[0[1[4 Metallated methylenephosphines\ LnM"X#C1PY 5895[11[0[1[5 C\C!diheterosubstituted methylenearsines\ X1C1AsY 580

5[11[0[2 Tricoordinate Phosphorus Derivatives 5805[11[0[2[0 Stabilized ðX1C1PY1Ł

¦ species 5805[11[0[2[1 Functions with a phosphorus!metal s!donor bond\ X1C1P"MLn#Y 5815[11[0[2[2 s2l4!Methylenephosphoranes\ X1C1P"1Z#Y 581

5[11[0[3 Tetracoordinate Phosphorus Derivatives 5835[11[0[3[0 Dihalosubstituted ylides\ Hal1C1PY2 5835[11[0[3[1 Oxyèn!\ sulfur!\ and selenium!substituted ylides\ RE"X#C1PY2 "E�O\ S\ or Se# 5865[11[0[3[2 Nitroèn!\ phosphorus!\ arsenic! and antimony!substituted ylides\ R1E"X#C1PY2

"E�N\ P\ As or Sb# 6995[11[0[3[3 Silicon!\ èrmanium! and boron!substituted ylides\ R2E"X#C1PY2 "E�Si or Ge#

and R1B"X#C1PY2 6915[11[0[3[4 Metal substituted ylides\ LnM"X#C1PY2 694

5[11[0[4 Tetracoordinate Arsenic\ Antimony and Bismuth Derivatives 6965[11[0[4[0 C\C!Diheterosubstituted arsonium ylides\ X1C1AsY2 6965[11[0[4[1 Stibonium and bismuthonium ylides bearin` heterosubstituents\ X1C1EY2 "E�Sb or Bi# 697

5[11[1 FUNCTIONS CONTAINING A DOUBLY BONDED METALLOID 698

5[11[1[0 Tricoordinate Silicon and Germanium Derivatives 6985[11[1[0[0 Disilylsubstituted silaethenes\ "R2Si#1C1SiY1 6985[11[1[0[1 C\C!Diheterosubstituted èrmaethenes\ X1C1GeY1 609

5[11[1[1 Functions Incorporatin` a Doubly Bonded Boron 6015[11[1[1[0 Methyleneboranes\ X1C1B0Y 6015[11[1[1[1 1!Borataallenes\ ðX1C1B1CY1Ł

− 604

566

567 Doubly Bonded P\ As\ Sb\ Bi\ Si\ Ge\ B or a Metal

5[11[2 FUNCTIONS INCORPORATING A DOUBLY BONDED METAL 605

5[11[2[0 Transition Metal Carbene Complexes 6055[11[2[0[0 Dihalocarbene complexes\ Hal1C1MLn 6065[11[2[0[1 Oxy`en!\ sulfur! and nitro`en!substituted carbene complexes\ RE"X#C1MLn

"E�O or S# and R1N"X#CMLn 6085[11[2[0[2 Silicon!substituted carbene complexes\ R2Si"X#C1MLn 612

5[11[2[1 Functions With a Formal TinÐCarbon Double Bond 613

5[11[0 FUNCTIONS CONTAINING DOUBLY BONDED P\ As\ Sb or Bi

5[11[0[0 General Remarks

The chemistry of functions X0X1C1E "X0\ X1�heteroatom substituents\ E�P\ As\ Sb\ or Bi#featuring a double bond between carbon and the heavier Group 04 elements is centered largelyaround phosphorus[ The latter forms four types of isolable compounds "0Ð3# containing a formalC1P bond[

(1) (2) (3) (4)

P

X2

X1

P

X2

X1 Y

Y

P

X2

X1 Z

Y

Y P

X2

X1

Y

Y

Y

+

In contrast to the phosphorus species the chemistry of their arsenic analogues is in its infancy[Although several structural types of the coordinatively unsaturated arsenic derivatives are known\information about C\C!diheterosubstituted species X0X1C1As"Z#n"Y#m is very sparse[ There is noexperimental evidence for double bonding between a X0X1C unit and trivalent or tetravalentantimony or bismuth[

5[11[0[1 Dicoordinate Phosphorus and Arsenic Derivatives

The compounds X0X1C1EY "E�P\ As# are currently named in Chemical Abstracts as methyl!enephosphines or methylenearsines[ They possess a genuine "pÐp#p double bond and can be regardedas the heavier congeners of alkenes[ The chemistry of phosphaalkenes is documented by twomonographs ðB!77MI 511!90\ B!89MI 511!90Ł and by several comprehensive reviews ð70AG"E#620\75ZOB142\ 78T5908Ł that appeared in the last decade[ Individual aspects of phosphaalkene chemistryhave been covered in numerous review articles[ The most important of these are by Becker\ Beckerand Mundt ð72PS"03#156Ł\ Kroto ð71CSR324Ł\ Lutsenko ð73ZC234Ł\ and Grobe and co!workersð75PS"17#128Ł[ The methods of preparation of the low coordinate arsenic compounds have beenreviewed by Dianova and Zabotina ð80RCR051Ł[ This section concerns functions with two het!eroatomÐcarbon bonds\ whatever the nature of substituent on the phosphorus or arsenic[ Functionsof the type R"X#C1EY "E�P\ As^ R�Alk\ Ar# are discussed in Chapter 4[12[

Simple heterosubstituted phosphaalkenes and arsaalkenes like F1C1PH\ "MeO#1C1PPh orCl1C1AsPh are very unstable[ They polymerize rapidly\ forming\ dependent on the conditions\dimeric or oligomeric compounds "X0X1CEY#n with C0E s!bonds[ Special kinetic or ther!modynamic factors are required to increase the stability of X0X1C1EY species ð70AG"E#620\ 89MI511!90Ł[ Three general synthetic methods are applied to prepare the X0X1C1PY functions] "i# the0\1!elimination reactions of suitable organophosphines\ "ii# condensation reactions\ and "iii# 0\2!trimethylsilyl migration "Scheme 0#[ All other methods are of relatively minor importance and areused only in special cases[ Table 0 surveys the diversity of the known C\C!diheterosubstitutedphosphaalkenes reported to date with an example from each major class[ The list indicates thesection in which speci_c phosphaalkene is covered and also the routes used for its synthesis[

5[11[0[1[0 Dihalomethylenephosphines\ Hal1C1PY

The synthesis of compounds having this structure has been the subject of extensive investigations\largely because of the ease of making stable molecules of this kind and because of the interesting

568P\ As\ Sb Or Bi

P

Z

YR

X2

X1

X2

X1

R

R+ P Y

Z

Z

P

X1

Z SiR3

Y

P

X2

X1

Y

1,2-elimination

–RZ

condensation

–2 RZ

1,3-silatropy

RZ = HHal, TMS-Hal, (TMS)2O, Cl2

RZ = HHal, MHal, MeOH, TMS-F

Z = O, S, NR

Scheme 1

properties which they possess[ These phosphaalkenes allow derivatization at the sp1!hybridizedcarbon and they are therefore valuable synthons for the preparation of a large variety of novelfunctions\ such as Hal"X#C1PY\ X0X1C1PY and XC2P[ Practically all synthetic routes to thedihalomethylenephosphines are based on 0\1!elimination reactions[

As already noted\ F1C1PH is extremely unstable[ It has been identi_ed by microwave spec!troscopy as a product in the pyrolysis of CF2PH1 ð65CC402Ł or in the room temperature reactionsbetween CF2PH1 and solid KOH or NaOEt ð67JA335\ 68CC542Ł[ Unlike F1C1PH\ per~uoro!1!phosphapropene "4# containing a bulky CF2 group on phosphorus is stable enough to be isolatedin a pure state[ This compound was generated for the _rst time from the reaction of CF2PH1 withNaOMe ð54JCS5764Ł or ZnMe1 ð70IC2623\ 72IC1462Ł[ The product obtained by these methods isusually contaminated with other volatile substances and the starting phosphine[ In 0873 Grobe andLe Van developed a simple thermolysis procedure according to Equation "0# to produce "4# in almostquantitative yield ð73AG"E#609\ 76PS"29#390Ł[ The phosphaalkene formed at 09−2 torr is quenched fromthe gas phase at −085>C[ Unreacted starting phosphine is repeatedly fed through the hot zone untilthe conversion into "4# is complete[ The kinetic stability observed for the phosphaalkene "4# is ratherhigh^ thus\ in ca[ 09) toluene or pentane solutions the dimer is _rst detectable after about 09 h at14>C[ Therefore\ handling in vacuum lines and reactivity studies in organic solvents are possibleunder ordinary conditions[

F3C P

SnMe3

CF3

300–340 °C

10-3 torrP

F

F

CF3 + Me3SnF (1)

(5)

In analogy to "4#\ 1!phospha!0!per~uorobutene "5# is obtained from stannylphosphine[ Thereaction leads to the isomeric phosphaalkenes "5# and "6# in a molar ratio of 2 ] 0 respectively"Equation "1## ð89ZN"B#037Ł[

(2)F3C P

SnMe3

CF2CF3

330 °C

10-2 torrP

F

F

CF2CF3 +

(6)

P

F

F3C

CF3

(7)

Attempts to synthesize perchlorophosphaalkene "7# by means of dehydrohalogenation ofdichloromethyldichlorophosphine with triethylamine yielded four!membered 0\2!diphosphetane "8#ð70ZOB1529Ł[ Evidence for the transient formation of phosphaalkene "7# comes from its trappingwith the conjugated dienes to give 1!chlorophosphinines "Scheme 1# ð78TL706Ł[

Dichloromethylenephosphines having bulky substituents on phosphorus such as bis"trimethyl!silyl#amino!\ N!trimethylsilyl!t!butylamino! or 1\1\5\5!tetramethylpiperidino groups\ enjoy highthermal stability[ These may be prepared by the reaction of Cl1CHPCl1 with the correspondinglithium or sodium amides "Scheme 2#[ For example\ sodium bis"trimethylsilyl#amide reacts withCl1CHPCl1 as a nucleophile and as a dehydrohalogenating agent to give the phosphaalkene "09# ingood yield ð70DOK"145#0390\ 70ZOB1529Ł[ The reaction of But"TMS#NLi with Cl1CHPCl1 gives rise


Table 0 Known types of C\C!diheterosubstituted methylenephosphines[

P

X2

X1

Y

X1 X2 Method Section number Example Ref.

F F a 6.22.1.2.1 84AG(E)710F2C=PCF3

Cl Cl a 6.22.1.2.1 84ZOB1520

Br Cl a 6.22.1.2.1 87ZAAC(553)7

Br Br a 6.22.1.2.1 89ZOB1902

I I a 6.22.1.2.1 89ZOB1902

RO F a, b 6.22.1.2.2 86ZN(B)149

RO RO a, b 6.22.1.2.2 84TL4447

RS RS a, b

Cl2C=PN(TMS)2

Br(Cl)C=PAr*

Br2C=PAr*

I2C=PAr*

MeO(F)C=PCF3

(TMS-O)2C=PPh

6.22.1.2.2 (BuiS)2C=PBut 85ZOB264

R2N F a 6.22.1.2.3 R2N(F)C=PCF3 86ZN(B)149

R2N RO a 6.22.1.2.3 Me2N(MeO)C=PCF3 91HC385

R2N RS b 6.22.1.2.3 Me2N(TMS-S)C=PBut 84ZAAC(518)21

R2N R2N d 6.22.1.2.3 (Me2N)2C=PH 85ZOB1188

R2P F a 6.22.1.2.3 Me2P(F)C=PCF3 86ZN(B)149

R2P Cl e 6.22.1.2.3 [Cl(Ar*)P]ClC=PAr* 89TL177

R2P Br e 6.22.1.2.3 [Br(Ar*)P]BrC=PAr* 89TL177

R2P RO b

P

P

But

But

P Ar

6.22.1.2.3 Ar*PH(TMS-O)C=PAr* 84AG(E)619

R2P RS e 6.22.1.2.3 Ar*PH(HS)C=PAr* 84AG(E)970

R2P R2N e 6.22.1.2.3 (R2N)2P(R2N)C=PNR2 86JA7868

R3Si Br d 6.22.1.2.3 TMS(Br)C=PAr* 84TL4109

R—P—P—R 6.22.1.2.3 88CB281

(R = Pri)

Ar = 2,4-But2-4-MeC6H2

R3Si a 6.22.1.2.4 (TMS)2C=PCl 81ZC357

R3Ge R3Si e 6.22.1.2.4 92IC3493

Li Cl d 6.22.1.2.5 Li(Cl)C=PAr* 88CL1733

LnRe RO 6.22.1.2.5 85AG(E)53

LnPt Cl d 6.22.1.2.5 91JA9379

P

TMS

X2(Me2N)Ge

Y

d

R3Si

P

Cp(NO)(CO)Re

TMS-O

But

P

Cl

Cl(Et3P)2Pt

Ar*

X = (TMS)2NY = 2,2,6,6-tetramethyl-piperidino

570P\ As\ Sb Or Bi

Table 0 "continued#

LnPt LnPt d 6.22.1.2.5 91JA9379

R3Sn Cl d 85TL3551Me3Sn(Cl)C=PAr*6.22.1.2.5

R3Sn 6.22.1.2.5dBr Me3Sn(Br)C=PAr*

P

Cl(Et3P)Pt

Cl(Et3P)2Pt

Ar*

85TL3551

dR3SiR3Sn P

TMS

X2(Me2N)Sn

Y6.22.1.2.5 92IC3493

X = (TMS)2NY = 2,2,6,6-tetramethyl-piperidino

Ar* = 2,4,6-tri-t-butylphenyl. a 1,2-Elimination. b 1,3-Trimethylsilyl migration. c Condensation reactions. d Reactions at peripheral substituents.e Miscellaneous.

X1 X2 Method Section number Example Ref.

(9)P

ClCl

Cl

PCl2Cl

Cl

P

RR

ClCl

Cl

P

Cl

R R

P

P

Cl

Cl

Cl

ClCl

Cl

–2 HCl

Et3N

–HCl

(8)

20 °C

73%

RR

Et3N, benzene

5h, 80 °C

Scheme 2

1/2

R = HR = Me

33%35%

to the phosphaalkene "01# ð73ZOB0419Ł[ The dibromo!substituted methylenephosphines are alsoavailable by this method "00#\ however\ the di.culties of synthesizing starting dibromophosphineBr1CHPBr1 essentially limit this synthetic methodology[

PCl2X

X

R2NNaP

X

X NR2

X

P

X

X

NR2

P

Cl

Cl

N

R

But2 But(R)NLi

58%

(12)

(10) X = Cl(11) X = Br

76%70%

R2NNa

R = TMS; X = Cl, Br

Scheme 3

A simpler synthesis of dichloromethylenephosphines involves dechlorination of the compounds"02# with tris"diethylamido#phosphite as shown in Scheme 3 ð77ZOB0812Ł[ Trichloromethyl!phosphines "02# are accessible through a one!pot synthesis starting from R1NPCl1 and the two!component system CCl3:"Et1N#2P ð77ZOB371Ł[ Treatment of the bulky phosphites R1NPCl1 withCCl3 and But

2P in a molar ratio of 0 ] 0 ] 1 allows the preparation of the phosphaalkenes withoutisolation of the intermediate trichloromethylphosphines ð77ZOB0812Ł[

Phosphaalkenes Hal1C1PPh are not stable enough to permit isolation[ Methyl\ isopropyl ort!butyl substituents in the 1!\ 3!\ and 5!positions of the phenyl ring greatly increase the kineticstability[ Thus\ the compound "03# is air! and moisture!sensitive but very thermally stable "until


Cl P

CCl3

NR2

(13)

(13) P

NR2Cl

Cl

CCl4 + R2NPCl2 + (Et2N)3P–60 °C, ether

60–78%+ (Et2N)3P+Cl Cl–

(Et2N)3P

0 °C, ether, >95%CCl4 + R2NPCl2

R2N = Pri2N, But

2N, N

2 But3P

0 °C, ether

Scheme 4

049>C#^ it can be stored without change for months in an inert atmosphere[ The best route to "03#is the reaction of dichloromesitylphosphine with the system CCl3:"Et1N#2P ð81ZOB837Ł[Dihalomethylenephosphines "04# ð77CB170Ł and "05#Ð"08# which are sterically protected by the 1\3!di!t!butyl!3!methylphenyl or 1\3\5!tri!t!butylphenyl groups are not sensitive towards air[ Di~uoro!and dichloromethylenephosphines "05# ð76ZAAC"442#6Ł and "06# ð80CB1566Ł have been isolated ingood yield "53) and 62)# from the reaction of chloro"trihalomethyl#phosphines with n!butyl!lithium "Scheme 4# and dichloromethylenephosphines "04# and "06# ð74TL2440Ł were isolated inmoderate yields from the reactions of trichloromethylphosphines with 0\4!diazabicycloð4[3[9Łundec!4!ene "dbu# "Schemes 5 and 6#[ Although the latter methods are also applied to the synthesis ofdibromo! and diiodomethylenephosphines\ the more practical route to the compounds "06#Ð"08#starts from dichloro"1\3\5!tri!t!butylphenyl#phosphine[ This compound reacts with the two!com!ponent system CHal3:"Et1N#2P "Hal�Cl\ Br# in ether to give phosphaalkenes "06# and "07# "Scheme7# ð78ZOB0891Ł[ Extension of this procedure to the preparation of diiodomethylenephosphines "08#was unsuccessful[ However\ in the presence of tris"t!butyl#phosphine\ Ar�PCl1 "Ar��1\3\5!tri!t!butylphenyl# reacted smoothly with CHI2 to give the compound "08# in good yield "Scheme 8#[

P

Cl

ClP

Cl

Cl

But

But

(14) 70% (15) 41%

P

X

X

But

But

But

(16) X = F(17) X = Cl(18) X = Br(19) X = I

64% ⟨87ZAAC(553)7⟩62% ⟨89ZOB1902⟩; ⟨85TL3551⟩; 73% ⟨91CB2677⟩63% ⟨89ZOB1902⟩; ⟨85TL3551⟩; 55% ⟨91CB2677⟩34% ⟨89ZOB1902⟩; 93% ⟨91CB2677⟩

X3C PCl2 X3C P

Cl

Ar(16)

ArLi BunLi

X = F ⟨87ZAAC(553)7⟩ , Cl ⟨91CB2677⟩

Scheme 5

572P\ As\ Sb Or Bi

Ar P

H

Li

CCl4Cl3C P

H

Ar

dbu(15)

Scheme 6

Scheme 7

P

Cl

Ar

dbu(17)

Cl

Cl

ArPCl2 + CHal4 + 2 Et3P (17) or (18) + 2 Et3PHalCl

Scheme 8

Scheme 9ArPCl2 + 2CHI3 + 2 But

3P (19) + 2 But3P(Cl)I

The only known mixed chlorobromomethylenephosphine Cl"Br#C1PAr� has been obtained byaddition of bromine to the phosphaalkene H"Cl#C1PAr� "in turn obtained by base!catalyzedcondensation of Ar�PH1 with trichloromethane ð73AG"E#784Ł followed by dehydrohalogenation ofthe intermediate phosphine ClBr1CHP"Ar�#Br ð76ZAAC"442#6Ł#[

5[11[0[1[1 Oxygen! and sulfur!substituted methylenephosphines\ RO"X#C1PY and RS"X#C1PY

"i# Synthesis by dehydrochlorination reactions

Per~uoro!1!phosphapropene "4# reacts with alcohols to yield phosphines "19# which can be readilydehydrohalogenated to ~uoro"alkoxy#methylenephosphines "10#[ Sulfur!substituted methylene!phosphines could not be obtained by such a reaction because addition of thiols to "4# leads tocompounds having the structure "11# "Scheme 09# ð75ZN"B#038Ł[ In the presence of Pri

1NH thephosphines "19# react with AlkOH to give the phosphaalkenes AlkO"RO#C1PCF2[ With Et1NH\the compound F2CP"H#CO1Me undergoes an additionÐelimination process yielding the pushÐpullsystem Et1N"F#C1PCO1Me[ Phosphaalkenes "10# react with primary amines AlkNH1 "Alk�But\Me# with stereoselective formation of the fairly labile phosphaalkenes AlkNH"RO#C1PCF2

ð82ZN"B#47Ł[

P

F

F SMe

CF3

P

CF3

F

F

P

F

F

RO

H

CF3

P

CF3

F

RO

ROH

87–100%

Et3N

CHCl3, 20 °C>95%

MeSH

80%

(5) (20) (21)(22)

R = Me, Et, Pri, PhCH2

Scheme 10

Base!induced dehydrohalogenation is the best method for producing bis"alkylthio#methyl!enephosphines from readily available chlorophosphines "12# or "14# ð76PS"29#322Ł[ For instance\the compound "12# underwent dehydrochlorination when treated with an equimolar amount oftriethylamine "Equation "2## ð74ZOB153\ 74ZOB1686Ł[ Similarly\ compounds "15# may be prepared bytreatment of the chlorophosphines "14# with "TMS#1NLi "Equation "3## ð72ZOB362\ 74ZOB153Ł[Phosphaalkenes "13# are at the borderline of kinetic stability[ They are stable in solution up to 9>Cbut dimerize to 0\2!diphosphetanes within a few hours at ambient temperatures[ The displacementof a chloride from "13# by various kinds of nucleophiles such as primary or secondary amines andphosphines has been used for the preparation of novel P!functionalized phosphaalkenes ð74ZOB153Ł[

PCl2RS

RS

P

Cl

RS

RS

Et3N

–10 °C, ether90–95%

(24)(23)

R = Me, Bui

(3)


P

RS

RS

P

Y

RS

RS

(TMS)2NLi

–30 °C, THF50–90%

(25)

Cl

Y

Y = But, (TMS)2N

(4)

(26)

"ii# Synthesis by reactions includin` ð0\2Ł!silyl mi`ration

ð0\2Ł!Silyl migration is one of the most useful routes to numerous functions of the typeTMSO"X#C1PY or TMSS"X#C1PY[ The method is based on the ð0\2Ł migration of a P!silyl groupto doubly bonded oxygen or sulfur and is usually used in combination with the preceding additionor condensation reactions[

Scheme 00 illustrates the formation of oxygen! and sulfur!substituted functions X1C1PY viainsertion of carbon dioxide ð73TL3336Ł or carbon disul_de ð79ZAAC"352#033\ 73ZAAC"406#64\73ZAAC"406#78Ł between the P0Si bond followed by silyl migration[ Another possibility to generatethiol!substituted phosphaalkenes starts from lithium silylphosphide Ar�P"Li#TMS "Ar��1\3\5!tri!t!butylphenyl# which readily reacts with CS1 forming the lithium sul_domethylene!phosphineTMS"LiS#C1PAr� ð77MI 511!91Ł[

CO2

HMPA, 20 °C

CS2

DME, 20 °C82%

RP(TMS)2

TMS-O PTMS

O

R

P

R

TMS-O

TMS-O

P

R

TMS-S

TMS-S

S

–S P(TMS)2R

Scheme 11

+

R = Me, But, Ph

R = Me, But, Ph, Mes

HMPA = hexamethylphosphoramide

Although the method is successful for some other types of heterocumulenes "vide infra#\ it is notgeneral[ Depending upon the nature of the heterocumulene\ interaction of the reagents may lead tothe phosphaalkene or the reaction may be terminated by the formation of addition product[ Arylisocyanates ð68ZAAC"348#76\ 58JCS"C#1991Ł\ aryl isothiocyanates ð74ZAAC"419#019\ 74ZAAC"419#028Ł\ anddiphenylketene ð70ZOB1078Ł react with silylphosphines to give only addition products[

As it will be seen below some trimethylsilyloxy!substituted phosphaalkenes may be obtained fromsilylphosphines "TMS#1PR or "TMS#2P and carbonic acid halides[ However\ this method does notwork in the case of chlorides of the type ROC"O#Cl ð79ZOB122Ł or R1NC"S#Cl ð73ZAAC"407#10Ł[

A variant of the ð0\2Ł silatropic methodology is provided by the reaction of phosphenimidousamides "16# with 1!lithium!1!trimethylsilyl!0\2!dithiane[ The reaction proceeds via nucleophilicdisplacement at the dicoordinated phosphorus atom with subsequent silyl migration from carbonto nitrogen "Scheme 01# ð73ZOB854Ł[

S

S

TMS

Li

S

S

TMS

P

S

SP(TMS)2N NR

NRP N

TMS

R+

–78 °C, THF

–(TMS)2NLi

~[TMS]

59–68%

R = But, TMS

Scheme 12

(27)

5[11[0[1[2 Nitrogen! and phosphorus!substituted methylenephosphines\ R1N"X#C1PY andR1P"X#C1PY

"i# From C\C!dihalomethylenephosphines

There are several useful examples of the formation of amino!substituted phosphaalkenes startingfrom tri~uoromethylphosphines ð82PS"65#154Ł[ Thus ~uoro"amino#methylenephosphines "17# and

574P\ As\ Sb Or Bi

"18# have been prepared in high yields by reacting CF2PH1 or "CF2#1PH with Me1NH or Et1NH"Equations "4# and "5## ð77CB544\ 89CB1206Ł[ The reaction of di~uoromethylenephosphineF1C1PCF2 "4# with two equivalents of R1NH also gives phosphaalkenes "18# via a series of HFelimination and R1NH addition steps ð77CB544Ł[ A similar process has been employed for thesynthesis of the compound "29# "Scheme 02#[ The transformation can be carried out as a one!potreaction without isolating the known phosphaalkene "10# ð80HAC274Ł[ An alternative route tocompounds of type "29# could be the base!catalysed addition of alcohols to "18# followed by HFelimination[ In practice this route has failed because the aminomethylenephosphines do not reactwith alcohols[

F3CPH2

3 R2NH

40–60%PH

R2N

F

R = Me, Et, Prn

(5)

(28)

R = Me, Et, Prn

(6)(F3C)2PH3 R2NH

P

R2N

F

CF3

(29)

(5)ROH

P

CF3

HF

F

ROR2NH

P

CF3

F

RO

(21)

R2NHP

CF3

HF

R2N

ROR2NH

58%P

CF3

R2N

RO

(30)R = Me, Et

Scheme 13

Bis"amino#methylenephosphines have been suggested as intermediates in the reactions ofCl1C1PN"TMS#1 with "TMS#1NLi and But"TMS#NLi\ but they have not been detected directlyð78TL3702Ł[ However\ phosphino!substituted phosphaalkene "20# has been isolated and character!ized from the reaction of dichloromethylenephosphine "04# with 0\1!dipotassium diorganylphos!phides "Equation "6## ð77CB170Ł[

P

Cl

Cl

(15)

Ar*

K(But)P–P(But)K

n-pentane, –80 °C

P

PP

Ar*

But

But

(31)

(7)

Ar* = 2,4-But2-4-MeC6H2

"ii# Synthesis by condensation reactions

The simplest route for the synthesis of bis"amino#methylenephosphines is the condensation ofsilylphosphines with functionally substituted dihaloalkanes containing mobile halogen atoms[ Theformation of phosphaalkene "21# from bis"dialkylamino#di~uoromethanes and silylphosphines isillustrated in Equation "7#[ Due to the high a.nity of silicon for ~uorine\ the reaction proceedsunder mild conditions[ Yields are good to excellent in most examples ð71ZOB0814\ 89ZOB1127Ł[ Theuse of P"TMS#2 in the reaction makes it possible to obtain P!trimethylsilyl!substituted phos!phaalkenes "22# which are key compounds for the preparation of a broad spectrum P!functionalizedbis"amino#methylenephosphines "Equation "8## ð72ZOB0561\ 74ZOB110\ 74ZOB0326\ 76ZOB890\ 89ZOB1127\80ZOB390Ł[


(8)

Me2N

Me2N 20 °C

65–95%P

R(32)

Me2N

Me2NF

F+ (TMS)2PR

R = But, Ph, 2, 4, 6-But3C6H2

(9)–TMS-Cl

P

Y

R2N

R2N+ YClP

TMS(33)

R2N

R2N

Y = Ph3Ge, 20 °C, benzene, 75% ⟨85ZOB221⟩; Ph3Sn, 20 °C, benzene, 95%, ⟨85ZOB221⟩; But2P, 0 °C, ether, 80%

⟨90ZOB2238⟩; (TMS)2C=P, 0 °C, ether, >90% ⟨87ZOB901⟩; Ar*N=P, 0 °C, ether, 91% ⟨91ZOB401⟩

Unlike the covalent ~uorinated analogues\ the ionic imidoyl chlorides "23# react withtris"trimethylsilyl#phosphine in a 1 ] 0 ratio\ forming the mesomerically stabilized phosphaalkene"24# "Equation "09## ð72AG"E#434\ 73AG"E#892\ 76PS"29#384Ł[

2[(Me2N)2CCl]+Cl– + P(TMS)3

MeCN, 20 °C

32%P

Me2N

Me2N

NMe2

NMe2

Cl–+

(10)

(34) (35)

The successful alternative method for bis"amino#methylenephosphine synthesis involves reactionsof phosphines and metal phosphides with highly reactive masked carbonyl compounds[ For example\amide acetals condense with arylphosphines forming dialkylamino!substituted phosphaalkenesð79TL0030\ 72TL4774Ł[ Alkylphosphines are inert with respect to amide acetals[ However\ sodiumphosphides readily react with carbenium tetra~uoroborates giving phosphaalkenes "21# "Equation"00## ð70ZC396\ 70TL3364Ł[ The method is suitable for obtaining the P!hydrogen substituted derivative"21^ R�H# ð72ZC88Ł[

(11)[(Me2N)2(EtO)C]+BF4– + RPHNa

20 °C, THF

(32)

P

RMe2N

Me2N

"iii# Reactions involvin` trimethylsilyl mi`rations

There are some useful speci_c syntheses of the amino! and phosphino!substituted methyl!enephosphines based on the reactions of silylphosphines such as RP"TMS#1 and P"TMS#2 withcarbonic acid halides[ Phosgene ð68AG"E#358\ 72CB098Ł and isocyanide dichlorides ð68AG"E#762\71AG"E#337\ 71CB0506\ 72CB0762Ł were shown to undergo double substitution giving the phosphaalkenes"25# and "26# "Scheme 03#[

Cl2CO

(36)

P

RP

TMS-O

2 RP(TMS)2

Cl2C=NR1

R

TMS

(37)

PR

P

N

R

TMS

R1

TMSP

P

R1N

R

TMS

R

TMS

Scheme 14

In the reaction of COCl1 with ButP"TMS#1\ t!butylphosphaketene\ ButP1C1O\ has been detectedas an intermediate by 20P!NMR[ When the temperature exceeds −59>C it dimerizes yielding thecorresponding 0\2!diphosphetane[ The presence of silylphosphine in excess leads to the phos!phaalkene "25# ð72TL1528Ł[ Interaction of benzoylisocyanide dichloride with PhP"TMS#1 yields byhalosilane condensation the phosphaalkene "27#\ which then undergoes cyclization and phosphorus

576P\ As\ Sb Or Bi

to oxygen migration of the silyl group yielding the isomeric 0\2!azaphosphetidine "28# with anexocyclic P1C bond "Scheme 04# ð71CB1260Ł[

Scheme 15

N

Cl

Cl Ph

O2 PhP(TMS)2

P

P

N

Ph

TMS

Ph

TMS

Ph

O

MeCN, 20 °C

32%

N

P

TMS

P

Ph

Ph

TMS-O

Ph

(38) (39)

A number of amino! and phosphino!substituted methylenephosphines have been prepared byaddition of silylphosphines to heterocumulenes[ Examples of the successful application of thismethod are shown in Equations "01# ð79JOM"081#22\ 70SRI168Ł and "02# ð75TL0550\ 77ZAAC"445#6Ł[ Thesynthesis of "39# was achieved from 0\1!bisðbis"trimethylsilyl#phosphinoŁbenzene and diphenyl!carbodiimide ð74ZAAC"418#105Ł[ The treatment of silyldiphosphines TMS"R#PP"R#TMS by twomoles of 1\3\5!tri!t!butylphenylphosphaketene\ Ar�P1C1O\ leads to compounds "30# ð75CB1637Ł[The addition of Ar�P"H#TMS ð73AG"E#508Ł and But"RO#C1PR "R�TMS# ð75TL0550Ł to thephosphaketene Ar�P1C1O with the formation of the corresponding phosphaalkenes has beenreported[

PhN C NPh + RPY2

hexane, 20 °C

71–95%P

Ph(Y)N

Ph(Y)N

R(12)

R = Me, Cy, But, Ar; Y = TMS

X = O, PhN; Y = TMS

+ RPY2

hexane, 20 °C

52–62%2 Ar P C X R P

XY

P

Ar

XY

P

Ar

(13)

P[TMS(Ph)N]2C

P[TMS(Ph)N]2C

(40) (41)

P

P

R

R

P

TMS-O

P

TMS-O

Ar

Ar

Silylphosphine "31# containing the very bulky 1\3\5!tri!t!butylphenyl group reacts with thiophos!gene at −67>C to yield phosphaalkene "32# instead of the expected phosphathioketene[ The lattercan be regenerated from "32# by photolysis[ Its reaction with 1\3\5!tri!t!butylphenylphosphineprovides a convenient route to functionalized phosphaalkene "33# "Scheme 05# ð73AG"E#869Ł[

Ar*P(TMS)2 Ar* P C SCl2C=S

1/2S

PS P

Ar*Ar*

Ar*PH2

hν

P

P

HS

Ar*

H

Ar*

(44)

(42)

(43)

Ar* = 2, 4, 6-But3C6H2

Scheme 16

As noted previously\ alkyl! and aryl isocyanates react with silylphosphines to give the additionproducts which exist in the form of acylphosphides ð68ZAAC"348#76Ł[ In contrast to simple isocy!anates\ a reaction between a!methoxybenzyl isocyanate and ButP"TMS#1 led to the correspondingacylphosphide which underwent 0\1!elimination of TMS!OMe and ð0\2Ł trimethylsilyl shift fromphosphorus to oxygen\ to a}ord the functionalized phosphaalkene ð73ZOB604Ł[


"iv# Intramolecular rearran`ements

Diphosphiranes "34# formed in the reaction of diphosphenes with halocarbenes readily undergoa photoinduced rearrangement with migration of chlorine to the phosphorus atom ð76PS"29#384\78CC482\ 89JOC4649Ł[ The halocarbenes were generated by the reaction of ButOK or BuLi with anexcess of the corresponding haloform or alternatively from tetrahalomethanes and BuLi at lowtemperatures "Scheme 06#[ The scope of this method is restricted to 0\2!diphosphapropenes "35#containing very bulky substituents on phosphorus[

P P

R1

R2

[:CHal2]

pentane, 20 °C

PPR1 R2

Hal Hal

hν

50–80%Hal

P PR2Hal

R1

Scheme 17

R1, R2 = 2, 4, 6-But3C6H2

(45) (46)

5[11[0[1[3 Silicon! and germanium!substituted methylenephosphines\ R2Si"X#C1PY andR2Ge"X#C1PY

Starting in 0870 "with the synthesis of the _rst C!silylated phosphaalkene ð70ZAAC"362#74Ł\approximately forty stable silicon! and germanium!substituted methylenephosphines have beensynthesized so far\ the stability of which is due primarily to the presence of bulky silyl or germylsubstituents on the carbon atom ð77MI 511!90\ 89MI 511!90Ł[ Two principal methods for the preparationof the compounds include 0\1!elimination reactions and derivatization of the other types of low!coordinated phosphorus derivatives[

"i# Synthesis by elimination reactions

Several P!substituted bis"trimethylsilyl#methylenephosphines were obtained by dehydro!chlorination of the corresponding chlorophosphines "Scheme 07# ð70TL1048\ 70TL3846\ 74OM228Ł[Base!induced hydrogen halide elimination requires both strong and bulky bases to prevent nucle!ophilic substitution at the phosphorus atom or addition of the base to the P1C bond[ The bestreagents meeting these conditions are dbu and 0\3!diazabicycloð1[1[1Łoctane "dabco#^ triethylaminein most cases was not e}ective[

(TMS)2CHLiYPCl2

P

TMS

TMS Y

Cl

B

–HClP

Y

TMS

TMS

Scheme 18

Y = Cl, Br ⟨81TL2159⟩ , 2, 4, 6-Me3C6H2 ⟨85OM339⟩; B = dabco, dbu

The synthesis of bis"trimethylsilyl#methylenephosphines is sometimes more simple where the keystage is the thermal elimination of chlorotrimethylsilane[ The reaction is promoted by the energygained from Cl0Si bond formation and the reduction of steric hindrance at the phosphorus atomby cleavage of the bulky silyl group[ The latter circumstance is essential because sterically unhinderedhalophosphines\ containing the Hal0P0C0TMS skeleton\ are thermally quite stable[ Forinstance\ among the compounds TMSCH1PCl1\ "TMS#1CHPCl1 and "TMS#2CPCl1 only the last onesplits o} chlorosilane under su.ciently gentle conditions "049>C\ 9[90 torr#\ giving phosphaalkene"36# ð70ZC246Ł[ The syntheses of compounds "37# and "38# are examples of the use of chlorosilane

578P\ As\ Sb Or Bi

elimination methodology to obtain P!alkyl! and P!aryl!substituted phosphaalkenes "Scheme 08#ð70ZAAC"362#74Ł[

(TMS)3CLiYPCl2

ether, 20 °CP

TMS

TMS Y

Cl

150–200 °C0.01 torr

–TMS-ClP

Y

TMS

TMS

TMS

Scheme 19

(47)(48)(49)

Y = ClY = But

Y = Ph

74%23%69%

By analogy with the 0\1!dihalogen elimination of vicinal dihaloalkanes with electropositive metals\the dechlorination of P!chloro!a!chloroalkylphosphines with lithium provides an additional toolfor phosphaalkene synthesis ð70TL3846Ł[ The generality of this approach is restricted\ however\ bydi.culties in the preparation of the starting material[

"ii# Derivatization and rearran`ements

Treatment of the highly hindered phosphaalkene "49# with bromine leads to the compound "40#"Equation "03## ð73TL3098Ł[ When N!bromosuccinimide was utilized as a halogenating reagent\dibromomethylenephosphine was obtained ð74TL2440Ł[

Br2P

TMS

TMS

Ar*

P

TMS

Br

Ar*

(50) (51)

(14)

Ar* = 2, 4, 6-But3C6H2

P!Chloro!bis"trimethylsilyl#methylenephosphine "36# has a reactivity which is comparable to thatof the secondary chlorophosphines "R1PCl#[ It is therefore a key compound for the preparation ofP!functionalized derivatives such as alkoxy!\ alkylthio!\ amino! and phosphino!substituted deriva!tives ð70AG"E#620\ 71AG"E#108\ 77IC673\ 78S400Ł[ P!Fluoro!C\C!bis"trimethylsilyl#methylenephosphinewas obtained by exchange reactions with AgF ð73ZOB1799Ł\ and AgBF3 ð76ZAAC"434#6Ł[ Chlorinesubstitution at the two!coordinate phosphorus atom in "36# by bromine and iodine with TMS!Brand TMS!I proceeds as readily as with chlorophosphines ð73ZOB1799Ł[ The treatment of phos!phaalkene "36# with But

1AsLi gives a P!arsino!substituted phosphaalkene ð74ZOB0751Ł[ The couplingreactions of "36# with "R1N#1C1PTMS ð76ZOB890Ł and Ph2P1CH1 ð78TL5758Ł lead to the cor!responding diphosphabutadienes[ Even the selective replacement of the halogen by alkyl and arylgroups with organolithium and Grignard reagents can be accomplished under mild conditionsð73TL3098\ 73JA6904\ 74ZOB1103Ł[ The reaction of "36# with pentamethylcyclopentadienyllithium"Cp�Li# in hexane at room temperature a}ords moderate yields of the phosphaalkene"TMS#1C1PCp� ð74C166Ł[ P!"Ethynyl#phosphaalkenes were obtained in good yield by reacting "36#with alkynyl Grignard reagents ð73CB1582Ł[ Treatment of "36# with alkali metallates of molybdenumand tungsten yields the bis"trimethylsilyl#methylenephosphines in which metalÐligand fragments arebonded to the phosphorus ð74CC0576\ 75OM482Ł[ Another synthetic approach to the compounds"TMS#1C1P0MLn was developed by Niecke and co!workers ð74C166\ 76CC09Ł[ It is based oncleavage of the P0C bond of the phosphaalkene "TMS#1C1P0Cp� with complexes of the typeðM"CO#2"MeCN#2Ł "M�Mo\ W#[

There are several useful methods for the synthesis of silyl! and germyl!substituted phosphaalkenesbased on the reactions of other types of low!coordinate phosphorus compounds\ but none of thereactions is general ð76ZOB0322Ł[ For example\ the phosphaalkenes "42# have been synthesized fromthe aminoiminophosphines "41# by a reaction involving the nucleophilic displacement at the two!coordinate phosphorus atom with subsequent ð0\2Ł!silyl rearrangement "Scheme 19# ð73PS"08#078Ł[The mixed C!germyl!C!silyl!substituted phosphaalkenes\ X0X1

1Ge"TMS#C1PY\ have been recentlyobtained by reacting a stable phosphinocarbene ðTMS"X0YP#C]Ł "X0�Me1N\ Y�1\1\5\5!tetra!methylpiperidino# and germanediyls ðGeX1

1Ł "X1�"TMS#1N or Ar�NH# ð81IC2382Ł[


P N

R

(TMS)2N

+ LiC(TMS)3

THF, –78 °C

–(TMS)2NLiP NR

TMS

TMS

TMSP

TMS

TMS N TMS

R(52) (53)R = But, TMS

Scheme 20

5[11[0[1[4 Metallated methylenephosphines\ LnM"X#C1PY

HalogenÐlithium exchange reactions provide the most general method for the preparation ofmetallated methylenephosphines[ Thus\ the C0Cl bond in dichloromethylenephosphine "06# isselectively cleaved by n!butyllithium at −79>C in a mixture of ether and toluene ð74TL2440Ł[ Thesame lithio"chloro#methylenephosphine can be produced via the reaction of Br"Cl#C1PAr� with"TMS#1PLi ð76ZAAC"434#6Ł[ Alternatively\ the lithiated phosphaalkene "43# has been generated innear quantitative yield from phosphaalkene H"Cl#C1PAr� and t!butyllithium at −67>C in THFð77CL0622Ł[ The successive treatment of "06# with butyllithium followed by an electrophile such asTMS!Cl\ Me2GeCl or Me2SnCl gives trimethylsilyl!\ trimethylgermyl! or trimethylstannyl!sub!stituted methylenephosphines "44# "Scheme 10# ð74TL2440\ 80CB1566Ł[ At room temperaturelithiomethylenephosphine "43# is unstable and easily splits o} lithium chloride to yield the phos!phaalkyne Ar�CP ð77CL0622Ł[ A similar transformation has been described for C\C!dichloro!methylene!P!"1\1\5\5!tetramethylpiperidino#phosphine ð78ZOB1022Ł[

P

Ar*Cl

Cl

P

Cl

Li

Ar* P

Cl

Me3M

Ar*

(17) (54) (55)

BunLi

ether/toluene, –80 °C

Me3MCl

M = Si, Ge, Sn

Scheme 21

The silatropic route to the P1C bond formation represents an alternative strategy for thesynthesis of C!metallated methylenephosphines ð77CRV0216Ł[ For example\ treatment of the complexðRe"CO#1"NO#"h4!C4Me4#ŁðBF3Ł with LiP"R#TMS yields the phosphaalkenyl complexes "45#[ Thereaction involves formation of phosphino!carbonyl complexes via nucleophilic addition of phos!phide to a CO ligand prior to the ð0\2Ł!silyl migration from phosphorus to oxygen "Scheme 11#ð74AG"E#42Ł[ Cationic Fe and Ru complexes of the type ðM"h4!C4Me4#"CO#2Ł¦ react with lithiumphosphide LiP"Ar�#TMS analogously ð75CB0746Ł[

(55)

LiP(R)TMS

ether, –80 °C

20 °C

25–30%

Cp*

ReOC CO

NOOC

Re PTMS

Cp*

ONO

R

Scheme 22

OCRe P

Cp*

ONO-TMS

R

R = But, TMS

Another approach to metallated methylenephosphines is based on the oxidative insertion oftransition!metal complexes into the C0Hal bond of the C!halomethylenephosphine[ Angelici andco!workers used this method for preparing phosphaalkenylÐplatinum complexes "46# and "47#containing Pt0C s!bond "Scheme 12# ð80JA8268Ł[ Under similar conditions\ reaction of the phos!phaalkene "06# with Pd"PPh2#3 a}ords the phosphaalkyne\ Ar�CP[ The transformation was inter!preted as a multi!step process including the generation of the unstable palladium!substitutedmethylenephosphine\ Cl"L2Pd#C1PAr� "L�PPh2#\ and its subsequent conversion into phos!phaisocyanide which isomerizes to phosphaalkyne ð81TL1870\ 82OM3154Ł[

P

Cl

Cl

Ar*P

Cl

Pt

Ar*

ClL

LPt

PtP

Ar*

ClL

LCl

L

Scheme 23

PtL4

benzene, 20 °C85%

PtL4

benzene, 20 °C65%

Ar* = 2,4,6-But3C6H2; L = PEt3

(17) (57) (58)

580P\ As\ Sb Or Bi

5[11[0[1[5 C\C!diheterosubstituted methylenearsines\ X1C1AsY

Only sparse information is available concerning heterosubstituted arsaalkenes ð80RCR051Ł[ Thisneglect stems largely from the ease of their oligomerization and polymerization which not onlymakes them di.cult to isolate\ but hitherto has precluded their use in preparative chemistry[

Di~uoromethylenearsine\ F1C1AsCF2\ obtained by pyrolysis of a stannylarsine\ Me2SnAs"CF2#1\has been described by Grobe and Duc Le Van ð73AG"E#609Ł[ Despite its high reactivity\ the arsaalkenecould be unequivocally characterized by its 08F NMR spectrum at −009>C and _nally identi_ed byits dimerization products[

A dialkylamino group on sp1!hybridized carbon was found to stabilize methylenearsinesR1N"R#C1AsAr ð81PS"55#146Ł[ However\ no attempts have so far been made to obtain C\C!bis"amino#!substituted arsaalkenes[ An unexpected reaction leading to the formation of the stabletricyclic macroheterocycle "59# containing Si"N#C1As fragment was observed when silaarsene "48#was treated with 0\5!diisocyanohexane "Equation "04## ð82CC0474Ł[

Ar = 2,4,6-Pri3C6H2

Si As

Ar

Ar

SiPri3

toluene, –80 °C

(59)

(60)

CNNC

Si NN

SiNN

AsSiPri

3

AsPri

3Si

Ar

Ar

Ar

Ar(15)

5[11[0[2 Tricoordinate Phosphorus Derivatives

5[11[0[2[0 Stabilized ðX1C1PY1Ł¦ species

Stabilized ðX1C1PY1Ł¦ species are the heavier congeners of iminium ions ðX1C1NR1Ł¦\ and arenamed as methylenephosphonium ions[ They have been investigated only brie~y\ due primarily totheir low stability[ After several years of speculation about these species ð73JPC0870\ 75JA4284\76CC0288Ł Bertrand and co!workers were able to prepare\ isolate and characterize the _rst stablemethylenephosphonium salt "51# starting from the electron rich diazo compound "50# according toScheme 13 ð78JA5742Ł[ These same workers discovered that the diazo compound "50# reacts withtriethylboron in toluene at −79>C to give the borane!carbene adduct which can be regarded as amethylenephosphonium type compound ð82CC0243Ł[

Grutzmacher et al[ suggested the more general route to the compounds ðX1C1PY1Ł¦A− basedon chloride ion abstraction from P!chlorinated ylides as illustrated in Scheme 14 ð80AG"E#698\82CC562Ł[ The main side process is oxidation of the substrates by the system Al1Cl5ÐCH1Cl1 toradical cations ð"TMS#1CP"Cl#R1Ł=¦ and their subsequent transformation into chlorophosphoniumsalts ð"TMS#1CHP"Cl#R1Ł¦AlCl3− ð82PS"65#10Ł[ When P!chloro!P\P!bis"dialkylamino# substitutedylides react with Al1Cl5 in dichloromethane solution\ the side reaction now predominates and theonly reaction product is the phosphonium salt ð82PS"65#10Ł[

N2

TMS P(NPri2)2

P

NPri2

NPri2TMS

P

NPri2

NPri2

TMS P

NPri2

NPri2TMS

–

(61)

hν or ∆ +TMSCF3SO3TMS

Et2O, –78°C70%

+

CF3SO3–

(62)Scheme 24

Scheme 25

Li

TMS

TMS

P

TMS

TMS R

R

P

TMS

TMS R

R

Cl P

TMS

TMS R

R

+

AlCl4–

R2PCl

THF, –78 °C100%

CCl4

hexane, –78 °C100%

0.5 Al2Cl3

CH2Cl2, –78 °C


5[11[0[2[1 Functions with a phosphorus!metal s!donor bond\ X1C1P"MLn#Y

Phosphaalkene transition!metal complexes have been reviewed in 0874 by Scherer ð74AG"E#813Ł\in 0870 and 0878 by Appel and Knoll ð70AG"E#620\ B!78MI 511!90Ł\ and in 0877 by Nixon ð77CRV0216Ł[

Generally\ three synthetic methods can be applied to prepare h0"P#!coordinated methyl!enephosphines] "i# complexation of a phosphaalkene which already possesses the P1C double bond\"ii# the so!called {phospha!Wittig| synthesis ð89OM682\ 81ACR89Ł\ and "iii# an approach based on thereactions of terminal phosphinidene complexes ð76AG"E#164Ł "Scheme 15#[ However\ practically allknown C\C!diheterosubstituted phosphaalkene complexes X1C1P"MLn#Y were obtained by start!ing with compounds in which a phosphorus!carbon double bond already exists[ Table 1 summarizessome typical examples[ The formulation of the complexes was based on mass spectral and NMRdata and in many cases was con_rmed by single!crystal x!ray crystallographic studies[

P

YX2

X1

P

YX2

X1 MLn

O

X2

X1

Y P P

O OR

OR

LnMM1Ln

PMLnY

X1

X2

Scheme 26

P MLnY

+ MLn

ii iiiM1Ln

X2

X1–

+

i

+

MLn, M1Ln = Cr(CO)5, W(CO)5

∆

Table 1 h0!Metal complexes derived from C\C!diheterosubstituted phosphaalkenes[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐPhosphaalkene\ X0X1C1PY Rea`ent Complex Ref[X0 X1 Y*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐF F F2C Cr"CO#4"CH1Cl1# F1C1PðCr"CO#4ŁCF2 77CB544F Me1N F2C Cr"CO#4"THF# F"Me1N#C1PðCr"CO#4ŁCF2 77CB544EtO Me1N F2C Cr"CO#4"THF# EtO"Me1N#C1PðCr"CO#4ŁCF2 80HC274TMS TMS "TMS#1N Fe"CO#4 "TMS#1C1PðFe"CO#3ŁN"TMS#1 73OM0021TMS TMS Ar� Fe"CO#4 "TMS#1C1PðFe"CO#3ŁAr� 73TL3098TMS TMS Cl ðPtCl1"PEt2#Ł1 "TMS#1C1Pð"PEt2#Cl1ŁCl 81ZOB363TMS TMS Cl RhCl"PPh2#1 "TMS#1C1PðRhCl"PPh2#1ŁCl 78JOM"257#C18TMS TMS Me4C4 AgSO2CF2 ð"TMS#1C1P"Ag#C4Me4Ł

¦CF2SO2− 74C166

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐAr��1\3\5!tri!t!butylphenyl

5[11[0[2[2 s2l4!Methylenephosphoranes\ X1C1P"1Z#Y

Stable s2l4!methylenephosphoranes have been reported with Z�R1C\ O\ S\ Se and RN[ Thehetero substituents on the carbon atom "X# are almost completely restricted in the known examplesto silyl groups[

General aspects of the chemistry of s2l4!phosphoranes were covered in a recent monography ð81MI511!90Ł and several reviews ð70TCC60\ 71HOU"E0#472\ 75PS"15#216\ B!89MI 511!90Ł[ Tetrakis"trimethylsilyl#!substituted bis"methylene#phosphoranes\ ð"TMS#1C1Ł1PY\ can be obtained directly from organo!dichlorophosphines and lithium bis"trimethylsilyl#chloromethanide "vide infra#[ The synthesis ofother types of s2l4!methylenephosphoranes is based on 0\0!oxidative addition reactions to di!coordinated phosphorus derivatives[ Both methylenephosphines and iminophosphines can beemployed as substrates for the synthesis of methylene"imino#phosphoranes[ Since the stable oxo!\thioxo!\ and selenoxo!phosphines ðYP1O"S\Se#Ł are unknown\ the methods for preparingcorresponding phosphoranes consist of the reactions of methylenephosphines with elementaloxygen\ sulfur or selenium[

582P\ As\ Sb Or Bi

"i# From or`anodichlorophosphines

The bis"methylene#phosphoranes of type ðTMS#1C1Ł1PY can be obtained by reaction of thelithiated chlorobis"trimethylsilyl#methane with dichlorophosphines ð71AG"E#79\ 75CB424\ 77PS"25#036Ł[The synthesis is a three!step process as shown in Scheme 16[ All P!substituted bis"methyl!ene#phosphoranes bearing four silyl groups are thermally stable\ soluble in nonpolar solvents\ andsomewhat volatile[ Attempts to apply this approach to the synthesis of bis"methylene#!arsoraneswere unsuccessful[ Unlike the analogous phosphoranes\ bis"methylene#!arsoranes are unstable andisomerize within a short period of time into the stable arsiranes ð74AG"E#308Ł[

Y PCl2

LiCl

TMSTMS

P

Cl

Y Cl

TMS

TMS

LiCl

TMSTMS

P

Y TMS

TMS

LiCl

TMSTMS

P

TMS

TMS Y

ether/THF, –78 °C

Scheme 27

TMS

TMS

–LiCl–Cl2C(TMS)2

ether/THF, –78 °C55–80%

(63)

Y = Me2N, PhS, Ph2CH, C2H5CH(Me)

The reaction of PCl2 with three equivalents of "TMS#1CClLi leads to the stable bis"methyl!ene#chlorophosphorane "52^ Y�Cl# which is a key substance for the synthesis of other P!func!tionalized derivatives ð71TL1906Ł[ Another procedure to obtain this compound involves the reactionof bis"methylene#methoxyphosphorane ð"TMS#1C1Ł1POMe with BCl2[ The bromo! and iodo!sub!stituted compounds are also available by this method ð73ZC273Ł[

"ii# From methylenephosphines and iminophosphines

As shown in Scheme 17 the action of some carbenoids on phosphaalkenes a}ords monomericbis"methylene#phosphoranes of the type "53# ð75CB0866Ł[ The same approach has been employed forthe synthesis of some methylene"imino#phosphoranes[ For example\ when aminoiminophosphines\R1N0P1NR\ ð72ZOB582Ł or P!organoiminophosphines\ RP1NR\ ð80ZOB68Ł reacted with"TMS#1CClLi in THF at −099>C\ the corresponding methylene"imino#phosphoranes were isolatedin yields of 44Ð79)[ The mechanism postulated for the reactions includes addition of the organo!lithium derivative to the P1N bond followed by 0\1!elimination of lithium chloride[

P

Y

X1

X2

+ Li

X3

Cl

X4ether/THF, –78 °C P

X1

X2

Y

X3

X4

(64)

Entry123456

Y(TMS)2N

Et2NPri

2NBut

2, 4, 6-Me3C6H22, 4, 6-Me3C6H2

X1

ClCl

TMSHPh

TMS

X2

ClCl

TMSBut

PhTMS

X3

TMSTMS

HTMSTMSPh

X4

TMSTMS

HTMSTMSPh

Scheme 28

As an alternative to the synthesis of methylene"imino#phosphoranes from iminophosphines thereverse process\ namely the transfer of an imino group to methylenephosphine\ may be employedfor the preparation of these compounds[ Besides organic azides\ the synthetic application of whichin low coordinated phosphorus chemistry is widely discussed in references ðB!89MI 511!90\ 81MI 511!90Ł\ N!silylated chloroamines have been used as oxidants for methylenephosphines "Scheme 18#[The reaction was found to proceed via oxidative addition of the chloroamine to give a P!halogenated


ylide\ which is further converted into the methylene"imino#phosphorane by elimination of chloro!trimethylsilane ð78ZOB1020Ł[

Scheme 29

P

TMS

TMS

Y

N ClTMS

R

benzene, 0 °CP

TMS

TMS

Y

Cl

NR TMS

>20 °C

54–75%P

TMS

TMS Y

NR

R = But, TMS; Y = Ph, R2N

The methylene"oxo!\ thioxo! or selenoxo#phosphoranes\ X1C1P"1Z#R "Z�O\ S or Se#\ havebeen obtained by oxidation of the phosphaalkenes with ozone\ sulfur or selenium[ These tricoor!dinate pentavalent phosphorus species are stable only in the presence of sterically demandinggroups at the P1C bond[ Thus\ among the compounds X0X1C1P"1O#Y "X0\X1�heteroatomsubstituents# the methylene"oxo#!phosphorane "TMS#1C1P"1O#Ar� "Ar��1\3\5!tri!t!butyl!phenyl# is the only known stable compound ð73TL3098Ł[ The range of phosphoranesX0X1C1P"1S^Se#Y is somewhat larger than that of methylene"oxo#phosphoranes^ however\ thepossibilities for the synthesis of stable examples of these compounds are relatively limited ð70CC61\73CC587\ 73TL3098Ł[

5[11[0[3 Tetracoordinate Phosphorus Derivatives

Tetracoordinate phosphorus derivatives of the type X0X1CPY2 "methylenephosphoranes or phos!phonium ylides# have received considerable attention[ Their structure and chemical properties havebeen reviewed by several authors as part of a wider discussion of phosphonium ylide chemistryð71RCR0\ 71HOU"E0#505\ 72RCR0985\ 80RCR280\ 80COS"5#060Ł[ This survey covers only the major devel!opments in the synthesis of C\C!diheterosubstituted ylide functions^ readers are referred to pub!lications cited in the text for a more thorough treatment of other aspects of methylenephosphoranechemistry[

Structurally s3l4!methylenephosphoranes may be represented as hybrids of covalent\X0X1C1PY2 "ylene#\ and dipolar\ X0X1C−

0P¦Y2 "ylide#\ structures[ Hetero substituents at theylide carbon atom in~uence the stability of the compounds markedly since s!donor and p!acceptorgroups "e[g[\ electropositive elements# stabilize ylides\ whereas p!donors and s!acceptors "e[g[\electronegative elements# destabilize them ð68JA6058Ł[ Lifetimes of nonstabilized ylides vary fromseveral hours at ambient temperature to short periods at low temperatures[

Synthetic routes to the C\C!heterosubstituted phosphonium ylides are based on the followingprocedures] "i# the direct introduction of a methylene group "X0X1C# into tervalent phosphoruscompounds "PY2#^ "ii# the synthesis from phosphonium salts^ "iii# the oxidative ylidation of tertiaryphosphines containing a mobile hydrogen atom at the a!carbon atom and behaving as CH acids^"iv# the rearrangement of a!haloalkylphosphines into P!halogenated ylides[ The other methods ofsynthesis are used only in individual instances\ but they sometimes have an advantage over standardmethods[

5[11[0[3[0 Dihalosubstituted ylides\ Hal1C1PY2

C\C!Dihalomethylenephosphoranes are valuable synthons for the Wittig alkenation reactionsð51JA0634\ 78CRV752Ł[ Nevertheless\ the number of such compounds which have been isolated andcharacterized is rather limited[ Owing to their low stability and high reactivity dihalomethyleneylides are usually generated in situ and quenched with a carbonyl compound[

Barton and co!workers utilized such an in situ generationÐcapture methodology for the reactionsof tertiary phosphines "especially triphenylphosphine# with sodium chlorodi~uoroacetate and car!bonyl compounds "Scheme 29# ð56JOC0200\ 57JOC0743\ 60JFC"0#236\ 61JA719Ł[ Di~uoromethyl!

584P\ As\ Sb Or Bi

enetributylphosphorane\ F1C1PBun2\ has also been prepared in situ via the reaction of

tributylphosphine with sodium chlorodi~uoroacetate in N!methylpyrrolidone ð54JOC0916Ł[

CF2ClCO2NaPh3P

DIGLYME140–150 °C

PPh3

F

F OR1

R2

15–80%F

F R1

R2

Scheme 30

Triphenylphosphine assisted decomposition of mercurials\ PhHgCFCl1 ð65CAR"35#8Ł andPhHgCX1Br "X�Cl\ Br# ð54JOM"2#226Ł\ provided a route to a series of methylenephosphoranes"55#[ Mechanistic studies suggested the intermediacy of an ylideÐmercuric halide complex "54# whichdissociates to a}ord the reactive methylenephosphorane species "Scheme 20#[

Ph3PO

R1

R2

X2

X1 R1

R2

HgPh

Br

X1

X2 PPh3

X2

X1

PPh3

PhHg

X1

X2

X1 = X2 = Cl, Br; X1 = H, X2 = Cl, Br

Scheme 31

+Br– + PhHgBr

(65) (66)

The well known in situ synthesis of dihalomethylenephosphoranes involves the reaction of halo!form with potassium t!butoxide in the presence of tertiary phosphines[ This method has provedespecially successful for the formation of dihalomethylenetriphenylphosphoranes "Scheme 21#ð51JA743Ł[ Dichlorocarbene can also be generated from chloroform and 49) aq[ sodium hydroxidesolution under phase transfer conditions ð73T0412Ł[ Another e.cient route to dihalomethyleneylides is based on the dehalogenation of phosphonium salts with Group 1B metals ð68JOM"058#012\66JFC"09#020\ 64JOC1685Ł or suitable tervalent phosphorus derivatives ð71HOU"E0#505Ł[ The most directprocedure consists of interaction of phosphines with tetrahalomethanes "Scheme 22#[ Evidence hasbeen provided that the initial step of the reaction sequence is the formation of an ion pair formedvia attack of phosphorus on a halogen[ Subsequent recombination of the ion pair "in the absenceof a trapping agent# and dehalogenation of the resultant phosphonium salt results in the formationof the ylide and the dihalophosphorane[ The reaction is very simple to carry out in the laboratoryand is a good general preparative method[ In particular\ using this approach Appel and Veltmanwere able for the _rst time to isolate dichloromethylene!triphenylphosphorane in a pure stateð66TL288Ł[ From tertiary phosphines and mixed tetrahalomethanes di~uoro! and dichloro!methylenephosphoranes are formed preferentially ð64TL2678\ 65JA445Ł[ The addition of zinc dustproved to be favorable in the synthesis of the di~uoro ð68CL872\ 70TL0310Ł\ dibromo ð61TL2658\72TL2276Ł\ and diiodomethylenephosphoranes ð74CC185Ł[ Subsequent improvements include the useof activated magnesium instead of zinc ð81TL572Ł[ The method was also successful for a generationin situ of highly reactive tris"dialkylamido#phosphonium ylides containing a dihalomethylene groupð66TL0128\ 79S443\ 73JOC695Ł[

ButOK

heptane, 0 °C

OR1

R2

X

X R1

R2

PPh3

X

X

X = Cl, Br

9–81%CHX3 + PPh3

Scheme 32

X = Cl, Br; R = Alk, Ar, Alk2NScheme 33

R3PPR3

X

XCX4 { [X3C]– [R3PX]+ [X3CPR3] X– }

+ R3P+ R3PX2

In contrast to tertiary phosphines\ dialkyl! and diarylchlorophosphines do not react with tetra!halomethanes due to the low nucleophilicity of the phosphorus atom[ However\ di!t!butyl~uoro!phosphine can be converted into the ylides "56# by the reaction with tetrachloro! and


tetrabromomethane ð77ZOB1053Ł[ The compounds "56# are remarkably stable and can be recrys!tallized from pentane "Equation "05##[

X = Cl, Br; R = But

P

X

X

CX4 + 2R2PF35 °C, 72 h

92–95%

F

R

R

+ [R2P(F)X]+ X–

(67)

(16)

Dichloromethylene"amino#di~uorophosphoranes "58# have been produced in good yields fromthe phosphorane "57# by the reaction with amines followed by dechlorination with hexa!ethyltriamidophosphite "Scheme 23# ð89ZOB1703Ł[ The best method for preparing dichloro!methylenebis"amino#~uorophosphoranes "69# is based on the reaction of tetraalkyl!diamido~uorophosphites with carbon tetrachloride[ These ylides may be distilled and kept in aninert atmosphere without signi_cant decomposition ð76ZOB1683Ł[ P!Chlorinated analogues of theylide "69# can not be obtained by this route since they readily add tetraalkyldiamidochlorophosphitesto give the phosphonium salts "60# ð76ZOB1030Ł[ However\ the dechlorination of phosphonium salt"61# with hexamethyltriamidophosphite proceeded quite smoothly and enabled the ylide "62# to beprepared in high yield "Scheme 24# ð78ZOB848Ł[

P

Cl

Cl(Et2N)3P

ether, –30 °C62–75%

F

NR2

F

(69)

Cl3C P

F

FCl

NR2R2NY

ether–90 °C→ 0 °C

Cl3C P

F

FCl

Cl

Scheme 34

(68) R = Me, Et, Pri; Y = H, TMS

P

Cl

Cl NR2

F

NR2

(70) R = Me, Et, Pri

P C P

Cl Cl

Cl

NR2

NR2R2N

R2N

+

Cl–

(71) R = Et, Pri

Y2PI Cl3C PY2 Cl3C P

ClY

YP

Cl

Cl Cl

Y

Y(Et2N)3P

CH2Cl2, 20 °C90%

Cl–+Cl2(Et2N)3P/CCl4

(72) (73)Y = Pri2N

Scheme 35

A convenient method for the synthesis of P0Cl ylides containing a dihalomethylene groupinvolves 0\1"C to P#!halotropic rearrangement[ Lutsenko and co!workers obtained bis"dimethyl!amino#trichloromethylphosphine "63#\ which is stable at room temperature\ by an exchange reactionof dichloro"trichloromethyl#phosphine with dimethylamine[ The product was puri_ed by distillationin vacuum and was then converted into the P!chloro ylide "64# by boiling in dichloromethane"Scheme 25# ð74ZOB0083Ł[ It was shown that the rearrangement is strongly catalyzed by the phos!phonium salt ð"Me1N#1P"Cl#CCl2Ł¦Cl− ð77ZOB0350Ł[ Similar chlorotropic rearrangement wasobserved for trichloromethylphosphine "65#[ The latter\ in the absence of solvent\ in 1 h at roomtemperature is converted in 69) yield into ylide "66# "Scheme 26# ð78ZOB0893Ł[

Scheme 36

Cl3C PCl2 Cl3C P P

Cl

Cl NMe2

NMe2

ClCH2Cl2

45 °C, 2 h

Me2NH

(74) (75)

NMe2

NMe2

Other methods for the synthesis of dihalo ylides are restricted to examples including substitutionof a proton at the ylide carbon atom[ For example\ exchange of hydrogen atoms at the ylide carbonatom in the compounds R"H#C1P"F#"NEt1#1 "R�H\ Alk# by chlorine occurs on reaction withcarbon tetrachloride in ether at −09>C in yields of 69Ð74) ð78ZOB229Ł[ P!Halo ylides formed by

586P\ As\ Sb Or Bi

Scheme 37

R2PCl Cl3C P P

Cl

Cl R

R

Cl20 °C, 2 h

70%

(Et2N)3P/CCl4

(76) (77)

R

R

R = But

reaction of tervalent phosphorus compounds with carbon tetrahalides may also react with a secondmolecule of CCl3 or CBr3 exchanging a hydrogen atom at the a!carbon atom by an atom of halogenð77ZOB380Ł[ The preparative applicability of this approach\ however\ seems to be limited[

5[11[0[3[1 Oxygen!\ sulfur!\ and selenium!substituted ylides\ RE"X#C1PY2 "E�O\ S\ or Se#

Phosphorus ylides carrying at least one oxygen at the a!carbon atom are very unstable at roomtemperature and can only be generated and detected in situ ð50CB0262\ 51CB1403\ 53TL2212Ł[ Ylides ofthe type "RO#1C1PY2 have not yet been characterized[ Ab initio calculations show that substituentslike OH stabilize singlet carbenes but not the phosphonium ylides[ Therefore C0O substitutedmethylenephosphoranes have an enhanced tendency to dissociate\ in agreement with experimentalobservations ð75CB0220Ł[

The synthetic chemistry of C0S substituted phosphorus ylides is considerably richer than fortheir oxygen analogues[ Direct incorporation of "RS#1C units into tervalent phosphorus compoundsmay be achieved by the carbenoid method[ One of the earliest in situ syntheses involved the thermaldecomposition of p!toluenesulfonylhydrazone salts "67# in THF containing a severalfold excess oftriphenylphosphine "Scheme 27# ð53TL134Ł[ The reaction is not applicable to arylthiomethyl!enephosphoranes[ Subsequently\ Seebach and co!workers suggested an excellent one!pot synthesisof bis"phenylthio#methylene ylide "79# based on the reaction of tris"phenylthio#methyllithium "68#with phosphines "Scheme 28# ð61CB376Ł[ The reaction pathway was rationalized by assuming theexistence of an equilibrium between a carbenoid and a carbene[ Tris"phenylseleno#methyllithiumreacts with triphenylphosphine similarly to give the bis"phenylseleno#methylenephosphorane in54) yield ð61CB400Ł[ Comparison with the analogous sulfur ylide shows that PhSe groups stabilizeadjacent carbanionic centers nearly as well as PhS groups do[

NN(Na)Ts

RS

RS

(78)

PPh3

THF, ∆PPh3

RS

RSArCHO

64% RS

RS

Ar

R = Me, Et; Ar = 4-O2NC6H4

Scheme 38

R3P

24 h, 20 °C>77%

PR3

PhS

PhS

Li

PhS

PhS

PhSBuLi

THF, –30 °CSPh

PhS

PhS

(79) (80)R = Bun, Ph, MeO

Scheme 39

Methylenephosphoranes containing alkylthio or arylthio functionality may be readily synthesizedby the transylidation reaction of sulfenyl halides with two equivalents of an alkylidenephosphoraneð71HOU"E0#505Ł[ In methylenetriphenylphosphorane\ H1CPPh2\ both a!protons may be substitutedby sulfenyl groups[ The phenylthio and methylthio groups may also be introduced by N!methyl!N!phenylthioacetamide and dimethylsuccinimidosulfonium chloride[ These methods avoid the dis!advantage of requiring two moles of starting ylide as in the reaction with sulfenyl halidesð80COS"5#060Ł[

In a similar fashion\ seleno!substituted ylides can be synthesized using areneselenyl chlorides orbromides ð65JOM"003#170\ 68CB244Ł[ Mixed phenylseleno"phenylthio#methylenephosphorane "71# has


been prepared from chloromethyl phenyl sul_de via phenylthiomethylenephosphorane "70# "Scheme39# ð72CB0844Ł[

PhS ClPPh3

toluene14h, 110 °C

PhS PPh3+

Cl–BuLi

pentane/THF–50 °C

PPh3

PhS PhSeCl

THF, –50 °C49%

PPh3

PhS

PhSe

(81) (82)Scheme 40

Unlike bis"phenylthio#methylenetributylphosphorane "79^ R�Bun# which is stable enough to beisolated in pure state\ ylides of the type "73# can only be generated in situ[ These species have receivedincreased attention since they were shown to present great synthetic potential in the synthesis ofderivatives and analogues of bis"ethylenedithio#tetrathiafulvalene ð75T0198\ 82PS"63#168Ł[ The mostsimple synthetic route to ylides "73# is shown in Scheme 30[ Deprotonation of phosphonium salts"72# yields an ylide which can be trapped in good yield with a carbonyl compound to a}ord adithiafulvalene ð65TL2584\ 67JOC258\ 72TL2358\ 80S15Ł[ Taking into account the availability of startingmaterials and the usually high yields in all steps\ this is the method of choice for the synthesis ofylides "73# in cases where R0 and R1 equal H\ alkyl\ or a condensed p!donor ring[ However\ thissequence of reactions cannot be employed for the preparation of ylides in which R0 and R1 areelectron!withdrawing groups[ The latter are available from the reaction of carbon disul_de!tri!n!butylphosphine adduct with activated carbonÐcarbon multiple bonds ð60JA3850\ 64CC859\ 68JOC829Ł[For example\ when the CS1ÐBu2P adduct is treated with a mixture of dimethyl alkynedicarboxylateand ~uoroboric acid etherate at −54>C\ the initially produced phosphorane "74# is trapped byprotonation\ and the resulting phosphonium salt "75# can be isolated in yields up to 61)[ Underaprotic conditions\ salt "75# can be used for the in situ generation of the unstable ylide "74# "Scheme31# ð68JOC829Ł[ The same approach has proved successful for the preparation of selenium analoguesof the ylide "74# ð73TL3116Ł[

X

XR 1

R2 X

XR1

R2

PR3

= H/H,

BuLi or Et3N

THF

R3P

MeCN, 20 °C>90%

X

XR1

R2 X

XR1

R2

PR3

,

R1

R2

,

+

OR2

R1

BF4– BF4

–

+

75–95%

(83)

(84)

R1

R2 S

SX = S, Se; R = Alkyl, Aryl;

Scheme 41

Bun3P

S

S–

CO2MeMeO2C

S

SMeO2C

MeO2C

PBun3

HBF4

BuLi S

SMeO2C

MeO2C

PBun3

Bun3P + CS2

+

(85) (86)Scheme 42

+

Among chalcogen!substituted phosphonium ylides\ those containing the bis"arenesulfonyl oralkanesulfonyl#methylene functionality are the most available[ Due to the e.cient stabilization ofa negative charge on the ylidic carbon atom by hexavalent sulfur\ these species are very stable andcan be synthesized directly from the dichlorophosphoranes and bis"arenesulfonyl#methanes in thepresence of triethylamine ð47CB326\ 71HOU"E0#505Ł[ The reaction of polychlorophosphoranes with

588P\ As\ Sb Or Bi

activated methylene compounds a}ords bis"arenesulfonyl#methylene ylides "76# with both one andtwo chlorine atoms at the phosphorus atom "Scheme 32# ð66ZOB1289\ 71ZOB0427Ł[

ArO2S SO2Ar P(Cl4–n)Phn

ArO2S

ArO2S+ PhnPCl5–n

Et3N

THF, –30 °C

P(Cl3–n)Phn

ArO2S

ArO2S

+Et3N

>50%Cl–

(87)

n = 1, 2; Ar = 4-XC6H4 (X = H, Cl, Me, MeO)

Scheme 43

Bis"benzenesulfonyl#halomethanes\ being comparatively strong CH!acids\ react with chloro!diphenylphosphine in the presence of triethylamine with the formation of tertiary a!haloalkylphos!phines "77#[ The latter rearrange smoothly into P!halogenated ylides "78#\ which are isolated ingood yield as stable crystalline compounds and are used as reagents in various chemical conversions"Scheme 33# ð66ZOR164Ł[ A successful alternative approach to the ylide species such as "78# utilizesreaction of bis"arenesulfonyl#methylenephosphines\ "ArSO1#1CHPY1\ with carbon tetrahalidesð68ZOB093Ł[ Electronegative arenesulfonyl groups at the a!carbon atom reduce the reactivity of thetervalent phosphorus atom towards the polyhaloalkanes[ However the reaction rate may in thiscase be increased by the addition to the reaction medium of tertiary amines[

X = Cl, BrPhO2S

PhO2S+ ClPPh2

Et3N

ether, 0 °C

(88)

X~ [X]

PhO2S

PhO2S

X P

Ph

Ph(89)

PhO2S

PhO2S

P

Ph

Ph

Scheme 44

X

Sulfonyl stabilized methylenephosphoranes are also available from simple ylides\ R"H#CPPh2

"R�H\ alkyl\ aryl# and sulfonic acid halides in a transylidation reaction[ However\ this method isfar from straightforward[ Aromatic and aliphatic sulfonyl ~uorides are most suitable for theintroduction of a sulfonyl group into the a!position of methylenephosphoranes[ Aliphatic sulfonylchlorides give only poor yields of alkanesulfonyl substituted ylides[ With aromatic sulfonyl chlorideshalogenation and sulfenation may occur instead of sulfonation ð61RTC26\ 63JOC1617Ł[

Hadjiarapoglou and Varvoglis have reported a more direct and general approach to bis"arene!sulfonyl or alkanesulfonyl#methylenephosphoranes based on transylidation with phenylio!donium ylides "Equation "06## ð77S802Ł[ The reaction is catalyzed by cupric acetonylacetonateand most likely involves the initial complexing of the reactants with the Cu atom\ followed bytransylidation[ Among ylides obtained by this method tris"ethoxy#phosphonium ylide "89\X0�X1�PhSO1\ Y�EtO# is of special interest because it is one of the few known stabletrialkoxyphosphonium ylides ð77S802Ł[ As a further development of this work the synthesis of ylidescontaining bis"per~uoroalkanesulfonyl#methylene functionality has been achieved by reaction ofphenyliodonium bis"per~uoroalkanesulfonyl#methide with phosphines ð82JFC"59#064Ł[

X2

X1

+ PY3

Cu(acac)2/CHCl3

48–92%IPh

X2

X1

PY3

(90)

(17)

X1, X2 = PhSO2, 4-MeC6H4SO2, MeSO2, –SO2(CH2)3SO2–; Y = Ph, OEt

Certain P!functionalized phosphonium ylides may be synthesized starting from bis"arene!sulfonyl#methylphosphine oxides\ "ArSO1#1CHP"O#R1\ which exist in solution in equilibrium withthe corresponding methylenephosphoranes ð72RCR0985Ł[ For example\ the reactions of the titlephosphine oxides with phosphorus pentachloride and diazomethane lead to the formation of thecorresponding P!chloro and P!methoxy phosphonium ylides ð71ZOB0427Ł[ It should be noted thatP!alkoxy substituted phosphonium ylides readily rearrange into phosphonates with migration ofthe alkyl group to the ylide carbon atom "the ylide version of the Pishchimuka reaction ð64CB1354Ł#[However\ since the electron!withdrawing arenesulfonyl substituents reduce the nucleophilicity of


the ylide carbon\ the compounds "ArSO1#1C1P"OR#R1 are considerably more stable than theirC!alkylated or arylated analogues[ The ylide "PhSO1#1C1P"OMe#Ph1 was reported to be stable onheating to 199>C ð68ZOB093Ł[

5[11[0[3[2 Nitrogen!\ phosphorus!\ arsenic! and antimony!substituted ylides\ R1E"X#C1PY2

"E�N\ P\ As or Sb#

Ab initio calculations predict thermal instability for the aminomethylenephosphoraneH1N"H#C1PH2 with respect to dissociation to phosphine PH2 and singlet carbene ðH1N"H#C]Łð75CB0220Ł[ In accordance with the theoretical data simple C!amino!substituted phosphoniumylides are extremely labile compounds[ Few examples of this class have been isolated and fullycharacterized[

The _rst stable methylenephosphoranes with a dialkylamino group at the ylide carbon atom wereprepared by Grobe and co!workers in 0878 ð78NJC252Ł[ It was reported that ~uorophosphaalkenes"18# reacted with tertiary phosphines according to Equation "07# to give the phosphorus ylide "80#[The rate of reaction under discussion strongly depends on both substituents R0 and R1 and is mainlyin~uenced by steric e}ects[ This is demonstrated by the fact that phosphaalkenes "18# do notreact with tri!t!butylphosphine and triphenylphosphine[ The ylides "80# show a surprising thermalstability] slow decomposition occurs only at temperatures above 49>C[ A 29) solution of thecompound "80^ R0�Me\ X�Me1N# in toluene does not change even on heating to 79>C for severalhours[ The unusual stability of the ylides "80# has been explained by electron delocalization in theplanar PIIICNPV skeleton aided by the electron withdrawing substituents CF2 and F on the tervalentphosphorus atom[ As a further development of this work the synthesis of ylides "81# and "82# withother p!donor substituents has been achieved by reaction of di~uoro! and ~uoro!"alkoxy#methylenephosphines with trialkylphosphines ð81CB456Ł[ Compounds "81# and "82# arestable up to about 09>C\ but decompose at higher temperatures yielding in the case of the C0Fsubstituted ylide di~uorotrimethylphosphorane as the main product[ Similar to the ylide "80# the~uorine and oxygen substituted ylides owe their existence to the electron withdrawing e}ect of theF2C"F#P unit which overrides the destabilizing in~uence of the ~uorine or alkoxy substituents onthe ylide carbon atom[

(18)F

X+ PR1

3

toluene

–196 to 20 °C30–100%

PP

X

PR13

(91)–(93)

CF3 F

F3C

(1); (21) and (29)

X = R2N (29, 91), F (5, 92), R2O (21, 93); R1, R2 = Me, Et

At least in a very formal sense\ one can consider the compound "84# produced by reaction oftrimethylphosphine with cationic carbyne complex "83# as a C!dialkylamino!substituted phos!phonium salt\ although it is obvious that the real bonding pattern of this cationic half ylide is muchcloser to the mesomerically stabilized zwitterionic structure "Scheme 34# ð67CB1340Ł[

[(CO)5Cr=CNEt2]+ [BF4]–

(94)

2 Me3P

CH2Cl2, –40 °C(CO)5Cr NEt2

PMe3

PMe3

BF4–

+

PMe3

Me3P

Et2N

Scheme 45

+BF4

–89%

(95)

Unlike nitrogen\ the heavier Group 04 elements\ especially phosphorus\ exert a stabilizing e}ecton the ylide functions and consequently numerous phosphino substituted phosphonium ylides havebeen synthesized and thoroughly investigated[ These will\ however\ despite their abundance\ betreated brie~y here because of the availability of a series of review articles that provide quick accessto the original papers published up to 0878 ð72RCR0985\ 80COS"5#060\ 80RCR280Ł[

The most general synthesis of phosphino substituted phosphonium ylides is based on trans!ylidation methodology\ investigated by Schmidbaur and co!workers in the early 0869s ð69AG"E#66\60CB049Ł[ This route in generalized form is outlined in Scheme 35[ Ylides carrying at least onehydrogen atom at the a!carbon atom react with chlorodialkyl! or chlorodiarylphosphines with

690P\ As\ Sb Or Bi

the formation of a!substituted phosphonium salts\ from which phosphino!substituted ylides aregenerated by deprotonation[ If the reaction provides a salt whose acidity is greater than that of thestarting ylide precursor\ a second mole of the starting ylide reacts with the zwitterionic intermediatein a transylidation reaction ð80COS"5#060Ł[ A large variety of phosphino substituted ylides have beenmade by this method ðB!61MI 511!90\ 80RCR280Ł[ The synthesis of arsenic! and antimony!substitutedylides may be carried out analogously[ From methylenetriphenylphosphorane and phosphorus\arsenic\ and antimony halogen compounds the corresponding disubstituted ylides such as "85#Ð"87#are available via double transylidation ð55LA"588#39\ 69JPR345\ 73OM27\ 73ZN"B#0345Ł[

PY3

X R2PClPY3

R2P

X+

Cl–B

HCl•BPY3

X

R2P

Scheme 46

PPh3

Ph2E

Ph2E

(96)(97)(98)

E = P ⟨66LA(699)40, 70JPR(312)456⟩E = As ⟨84ZN(B)1456)E = Sb ⟨84OM38⟩

Reactions of ylide anions with electrophiles lead directly to functionalized ylides ð76AG"E#68\76TL1000Ł[ For instance\ the ylide "88# can be metallated at the methyl group by LiMe\ NaNH1 orKH to give partially solvated products "099#[ The reaction of the latter with chloro!diphenylphosphine leads to the new ylides "090# and "091# "Scheme 36# ð72CB0275Ł[ Pure "090# isobtained from "099^ M�Li# and chlorodiphenylphosphine in the presence of TMEDA[

P

Ph2P Me

Ph

Ph P

Ph2P CH2

Ph

Ph

PPh2 PPh2

PPhPh

PPh2 PPh2

PPhPh

–

M+MeLi, NaNH2 or KH

PPh2

Ph2PCl

THF, –40 °C

(101) (102)

+

(100)

Scheme 47

(99)

The convenient procedure for the synthesis of methylenephosphoranes bearing phosphorus\arsenic or antimony at the ylidic carbon atom is condensation of trimethylsilyl!substituted ylideswith chlorophosphines\ chloroarsines and chlorostibines[ The reactions proceed in a 0 ] 0 ratio ofstarting reagents and are followed by elimination of chlorotrimethylsilane[ This method permitsaccess to compounds which are often di.cult to obtain by other routes and produces salt!freefunctionalized ylides in good yield[ The silylated precursors\ representing the starting materials forthe syntheses are readily available with a large variety of substituents "cf[ Section 5[11[0[3[3#[ Thereactions in both Equation "08# and Scheme 37 constitute examples from the literature whichillustrate the synthetic potential of the method[

P

Cl3Si Me

Cl

Me2 PCl3

benzene, 0 °C78%

Cl3Si

P

Cl2P Me

Cl

Me

Cl2P

(19)

PMe3

TMS

2 Me2PCl

ether, 0 °C94%

TMS

PMe3

TMS

PMe2P MeMe

+

Cl–MeLi

ether/THF, –30 °C54%

PMe3

TMS

Me2P

Scheme 48


Ylides bearing s2l4 and s1l2 phosphorus at the anionic centre are stable enough to be isolated[ Amethylenephosphorane bearing two!coordinate phosphorus at the ylidic carbon atom was obtainedby reaction of phosphonium salt "092# with three equivalents of sodium bis"trimethylsilyl#amide inTHF at −67>C[ Compound "093# is probably formed via ð0\2Ł!silyl migration[ According to an x!ray analysis\ this ylide can be described as a hetero allyl anion with a three!center!four!electronbond C00P00N0[ Oxidative addition of sulfur or selenium results in the formation of theimino"thioxo#phosphorane "094# or imino"selenoxo#phosphorane "095# "Scheme 38# ð80CB218Ł[

Cl2P P(NMe2)3 BF4– N P

TMS

TMS

C P(NMe2)3

P(NMe2)3

P

TMS

NTMS(104)

1/n Zn P(NMe2)3

Scheme 49

P

TMS

NTMS

+

(103)

Z

3 NaN(TMS)2

THF, –78 °C

(105)(106)

Z = SZ = Se

5[11[0[3[3 Silicon!\ germanium! and boron!substituted ylides\ R2E"X#C1PY2 "E�Si or Ge# andR1B"X#C1PY2

Trialkylsilyl groups exhibit a pronounced stabilizing e}ect on ylidic carbanions^ therefore\numerous silicon substituted phosphonium ylides are available and widely used in preparativechemistry[ A few review articles serve very well as introductions to this _eld ð64ACR51\ 80RCR280\80COS"5#060Ł[ Germanium! and boron!substituted phosphonium ylides are considerably less studied[

A wide variety of a!silylated methylenephosphoranes have been synthesized from simple methyl!enephosphoranes and chloroalkyl"aryl#silanes "especially TMS!Cl# by transylidation ð71AG"E#434\74AG"E#0957\ 81S676Ł[ From methylenetrialkyl"aryl#phosphoranes both mono! or bis!silylated prod!ucts may result "Scheme 49# ð56CB0921\ 81CB0942Ł[ Apart from the above mentioned silicon halogencompounds\ siletanes\ 0\2!disiletanes and the highly strained hexamethylsiliranes have been reactedwith methylenephosphoranes to give the corresponding silicon substituted ylides ð80COS"5#060Ł[ Theintroduction of germanium substituents may be carried out analogously or starting from ylideanions "Scheme 40# ð56CB0921\ 66CB566Ł[ Mixed silicon:germanium or silicon:tin substituted ylideswere synthesized by reacting the monosilylmethylenephosphorane "096# with germyl or stannylchlorides "Equation "19## ð56CB0921Ł[

Scheme 50

H2C PR3

TMS-Cl

–[MePR3]+ Cl– PR3

TMS TMS-Cl

–[TMS-CH2PR3]+ Cl–PR3

TMS

TMSR = Me, Ph

3 2

Scheme 51

H2C PPh3

2 Me3GeCl

Et2O, 20 °C51%

PR3

Me3Ge

Me3Ge

3

i, 2 LiRii, Me3GeCl

THF, –10 °C60%

H2C PMe3

PMe3

TMSPMe3

TMS

Me3M

Me3MCl

ether, 20 °C52–62%(107)

2 (20)

M = Ge, Sn

The reaction of methylenetrimethylphosphorane with dichlorodimethylsilane leads via a twofoldtransylidation to the formation of Si!bridged bisphosphorane "097# "Scheme 41# ð69CB86Ł[ Atelevated temperatures and in the presence of excess ylide as a catalyst\ the four!membered ring

692P\ As\ Sb Or Bi

undergoes an isomerization through ring expansion "097#Ð"098# ð63AG"E#439Ł[ Methylenetriphenyl!phosphorane reacts with 0\1!dichlorotetramethyldisilane to give a methylenephosphorane "009#with two exocyclic ylide functions "Equation "10## ð69AG"E#626Ł[

H2C PMe362 Me2SiCl2

ether, 35 °C55%

Si

SiMe3P PMe3

MeMe

Me Me

(108)

∆

Si

PSi

MeMe

MeMe

Me3PMe

Me

(109)

Scheme 52

H2C PMe36Et2O, 20 °C

17% SiMe2

SiMe2

Me2Si

Me2Si

Me3P

(110)

PMe3Si SiCl

Me

Me

Me

Cl

Me2+ (21)

A moderately important process for the preparation of silyl ylides is transsilylation[ This methodprovides a means of introducing more complicated substituents\ starting from simple trimethylsilylylides[ Equation "11# gives some selected examples[ As a rule these reactions proceed su.cientlyrapidly even at room temperature to give pure products in high yields^ the only by!product formedin the reactions is the readily separable chlorotrialkylsilane ð60CB049\ 69AG"E#66Ł[

PMe3

TMS

TMS

+ 2 RnSiHal4–n62–69%

PMe3

Rn(Hal3–n)Si

Rn(Hal3–n)Si

(22)

RnSiHal4–n = Me2SiCl2, MeSiCl3, SiCl4, Me2SiBr2, SiBr4, Me(ClCH2)SiCl2, ClCH2SiCl3, MeSiHCl2, HSiCl3, Me2SiFCl

The silicon substituted P!chloro ylides are available by 0\1"C to P# halotropic rearrangements oftrimethylsilyl substituted a!haloalkylphosphines[ The latter may in turn be prepared by reactingsilylalkylphosphines with tetrahalomethanes or condensation of perchlorinated carbosilanes withlithio! and silylphosphines[ The interaction of compounds of the type "000# with carbon tetrahalides"CCl3\ CBrCl2\ CBr3# is usually carried out in dichloromethane at room temperature or below 9>C[Yields of ylides obtained in this way are usually very high "Equation "12## ð68CB0957Ł[ However\ incertain cases tervalent phosphorus compounds containing trimethylsilyl groups on the a!carbonatom react with carbon tetrahalides with elimination of trihalotrimethylsilylmethane instead ofhaloform[ It should be noted that ylide "001# containing a trimethylsilyl group at the sp1!hybridizedcarbon atom is readily desilylated by excess of carbon tetrachloride to give carbodiphosphorane"002# "Scheme 42# ð68CB537Ł[

P

TMS

XCHal4

CH2Cl2, <20 °C

Y

Hal

YP

Y

YTMS

X(23)

(111)

Hal = Cl, Br; X = TMS, Ph, H; Y = Ph, R2N, RO

P

TMS

Ph2PCCl4

CH2Cl2, ∆

Ph

Cl

PhTMS

PPh2

PPh2

CCl4

87%P C P

Ph

Cl Cl

Ph

Ph Ph

(112) (113)

Scheme 53

The a\a!disilyl substituted P!chloro ylides have been prepared in good yields via the reactionof chlorocarbosilanes with lithio! or silylphosphines "Schemes 43 and 44#[ If C\C!dihalo!0\2\4!trisilacyclohexanes are used the major products are methylenephosphoranes "003# with exocyclic


ylide functions "Equation "13##[ These are stable crystalline substances or liquids distillable invacuum ð70ZAAC"361#34\ 73ZAAC"400#84Ł[

Scheme 54

Me2PLi

DME, –30 °CCl4–nC(SiCl3)n Cl3–n(SiCl3)nCPMe2 Cl2–n(Cl3Si)nC P

Cl

Me

Me

n = 1, 2

Scheme 55

Me2P-TMS

DME, ∆TMS

TMS

Cl

Cl

TMS

TMS

Cl

P Me

Me

TMS

TMS

P

Me

Cl

Me

Me2P-TMS

DME, –20 °C29–78%

SiR2

R2Si

R2SiHal

Hal

SiR2

R2Si

R2Si P

Me

Cl

Me

(114)Hal = Cl, Br; R = F, Cl, Me

(24)

P!Chloro ylides "004# containing trichlorosilyl groups on the a!carbon selectively exchange thechlorine atom on phosphorus for a dimethylphosphine group on interaction with lithium dimethyl!phosphide^ the trichlorosilyl groups are una}ected by this[ In addition\ during the reaction of ylide"004# with Me"TMS#PLi\ the P0P ylide "005# is formed which reacts with a second molecule of theP0Cl ylide and is converted into a double ylide with a P0P bond "006# "Scheme 45#ð73ZAAC"407#03Ł[

R(Me)PLi

Cl3Si

Cl3Si

P

Me

Cl

Me

(115)Cl3Si

Cl3Si

P

(116)

P

Me

Me Me

R (115)

R = TMS Cl3Si

Cl3Si

P

(117)

P

Me

Me SiCl3

SiCl3Me

Me

R = Me, TMS

+ ClP(Me)R

Scheme 56

It has been reported that photolysis of phosphinodiazomethane "007# in benzene at room tem!perature in the presence of an excess of chlorotrimethylsilane gives the ylide "008# in almostquantitative yield ð77JA5352Ł "Scheme 46#[ The generality of this approach is restricted by possibledi.culties in the preparation of the requisite phosphinocarbenes[

Dialkylborylalkylidenetriphenylphosphoranes have been studied rarely[ They are available viatransylidation starting from simple alkylidenephosphoranes and chlorodialkyl! or dichloro!alkylboranes ð73AG"E#270\ 75AG"E#448Ł[ The synthesis of the mixed siliconÐboron substituted ylide"019# follows the reaction pathway analogous to the approach to disilylated methylenephosphorane"008# "Scheme 47# ð82CC0243Ł[

The _rst C!gallyl!substituted phosphorus ylide\ "R1N#1P"Me#1C"TMS#GaMe1\ was recently pre!pared by the reaction of a stable phosphinocarbene with GaMe2 ð83AG"E#467Ł[

Scheme 57

hν, 300 nm

C6H6, 20 °C

(118)

TMS C P

NR2

NR2

R = Pri

– +TMS C P

NR2

NR2.. ..TMS P(NR2)2

N2

TMS C P

NR2

NR2TMS-Cl

C6H6, 20 °CP

TMS

TMS NR2

Cl

NR2

(119)

694P\ As\ Sb Or Bi

Scheme 58

TMS C P

NR2

NR2.. ..P

(MeO)2B

TMS NR2

NR2

P

(MeO)3B

TMS NR2

NR2

MeO P

(MeO)2B

TMS NR2

OMe

B(OMe)3NR2

(120)R = Pri

5[11[0[3[4 Metal substituted ylides\ LnM"X#C1PY2

Whereas the chemistry of the metal complexes of phosphorus ylides "010# has been the subject ofintensive investigation and has developed into a rapidly growing _eld of research with importantapplications ðB!71MI 511!90\ 72AG"E#896\ 72CCR0Ł\ the chemistry of metal substituted ylides "011# hasbeen investigated relatively little[ Moreover\ most of the examples that have been studied in detailare derived from the simple methylenephosphoranes\ H1CPY2[

PY3

–M+

PY3

M+

–

PY3

X

M

(121) (122)

Under this heading\ only the synthesis of functions of the type "011# which formally arise fromsubstitution of a hydrogen atom at the ylidic carbon by a metal atom will be considered[ Metalcomplexes of phosphonium ylides will not be discussed[

"i# Ylides with a Li0C bond

The synthesis of lithiated ylides by direct substitution of a proton at the a!carbon atom seems tobe restricted to alkylidenephosphoranes[

In 0871 Corey and co!workers reported that a!lithiomethylenetriphenylphosphorane "015# isavailable by reaction of the corresponding ylide with t!butyllithium in THF solution at low tem!perature ð71JA3613Ł[ The same lithium substituted ylide can be generated by reaction of methyl!triphenylphosphonium bromide with 1 equivalents of s!butyllithium in ether[ However\ examinationof the reactions by means of low temperature NMR spectroscopy showed that the interaction ofthe methylenetriphenylphosphorane with lithium alkyls includes replacement of a phenyl group atthe phosphorus atom by an alkyl group with formation of the ylide "012# "route a# and metallationof a benzene ring with formation of the ylide "013# "route b#[ Spectral characteristics of the lithiatedylide obtained by the exchange reaction of bromomethylenephosphorane "014# with t!butyllithiumin hexane at −64>C di}ered from those for the lithiated ylide prepared by direct metallation ð72C09\73TL3986\ 74TL0512Ł[ To explain these results it was proposed that lithium methylide "015# exists in ametallotropic tautomeric equilibrium with the ylide "013# lithiated in the benzene ring "Scheme 48#ð74TL444Ł[

PPh3

H2C

Ph

R

Ph H2C

Ph

Ph Li

BrPPh3

Li Li PPh2

RLi

b –RHa

H2C PPh3

–PhLi

ButLi

hexane, –75 °C

(123)

(124)

Scheme 59

(125) (126)


The reaction of methylenetrialkylphosphoranes with equimolar amounts of methyl! or butyl!lithium proceeds with lithiation of one of alkyl groups[ The use of excess of organolithium com!pounds leads to the formation of twofold lithiated ylides "016# "Scheme 59# ð70JOM"198#C09Ł[Metallation of silylated methylenetrialkylphosphoranes "e[g[\ TMS"H#C1PMe2# again occurs inthe alkyl groups and a}ords products with two carbanionic centers[

H2C P

R

Me

MeBuLi BuLi

– H2C

P

– H2C

Me

R+Li+

– H2C

P

– H2C+

– H2C R 2 Li+

(127)Scheme 60

The monomeric phosphonium ylides a!substituted by Group I metals other than lithium or byalkaline earth metals have not been described[

"ii# Ylides with a transition metalÐcarbon bond

The _rst attempts to obtain phosphonium ylides with a transition metal atom in place of the ylidehydrogen atom met with little success since the simplest reactions "e[g[\ of metal halides withH1CPR2# yield only insoluble products which are di.cult to characterize ð66ZN"B#747Ł[ Kaska andco!workers have successfully exploited the stabilizing in~uence of the h4!cyclopentadienyl groupto e}ect substitution of a proton at the ylide carbon atom by a "h4!C4H4#1ZrCl group[ Bis"h4!cyclopentadienyl#chlorozirconylmethylenetriphenylphosphorane "017# was isolated as yellow!orange needles in 64) yield[ In a similar fashion "h4!C4H4#1HfCl1 reacts with two equivalents ofmethylenetriphenylphosphorane in THF for 03 days at room temperature to give hafnium!sub!stituted ylide "018# "Equation "14## ð79ZN"B#0178Ł[

(25)(η5-C5H5)2MCl2 + 2 H2C PPh3

THF, 20 °C

–[MePPh3]+ Cl– PPh3

(η5-C5H5)2M

Cl

(128)(129)

M = ZrM = Hf

Subsequently the series of complexes of Group 3 metals with bridging ylide ligands has beendescribed[ Thus\ when the methylenephosphorane "029# containing bulky diethylamino groups onthe phosphorus atom was allowed to react with TiCl3\ the bis"phosphoranylidene#dititanacyclobutane "020# has been isolated in over 69) yield "Equation "15## ð75AG"E#463Ł[ Anal!ogously\ reaction of the ylide H1CPMe2 with TiCl1"NMe1#1 a}ords the 0\2!bis"dimethyl!amino#dititanacyclobutane ð66ZN"B#747Ł[ In both reactions the ylides are deprotonating in themanner of a transylidation\ giving rise to the formation of a phosphonium salt as a by!product[ Whenan excess of methylenetris"dimethylamino#phosphorane was treated with TiCl1"NMe1#1 according tothe same procedure "by employing the phosphorus methylide as base as well as nucleophile#\compound "021# having di}erent terminal ligands on titanium was obtained in 2) yield[ Theaddition of 1\3\5!trimethylpyridine to an equimolar mixture of ylide and TiCl1"NMe1#1 providedthe metallacycle "022# in 06) yield "Scheme 50# ð82AG"E#443Ł[ Use of TiCl2"NMe1# in place ofTiCl1"NMe1#1 a}orded "022# in the same isolated yield[ Compound "022# underwent ligand exchangereactions at titanium without disruption of the metallacycle core[ Thus\ the addition of 1[4 equi!valents of Ti"NMe1#3 to "022# at ambient temperature a}orded "021# in quantitative yield[ It shouldbe noted that because of their two oxophilic centers\ the metal!substituted ylides of type "022# maybe regarded as a synthetic equivalent for a carbon atom for the selective production of allenes fromunhindered aromatic aldehydes[ For example\ metallacycle "022# reacted immediately with an excessof 3!methylbenzaldehyde or 3!methoxybenzaldehyde in THF solution to give the corresponding0\2!diarylallenes in 32) and 39) isolated yield\ respectively\ based on an expected two equivalentsof allene per metallacycle "Equation "16##[ The compound "022# underwent the same reaction with3!methylbenzaldehyde in 19) yield ð82AG"E#443Ł[

696P\ As\ Sb Or Bi

4 TiCl4 + 6 H2C P(NEt2)3

Et2O/toluene, 20 °C

–2 [(Et2N)3PMe]2TiCl6

Ti

Ti(Et2N)3P P(NEt2)3

ClCl

Cl Cl

(26)

(130) (131)

2 TiCl2(NMe2)2 + 3 H2C P(NMe2)3

Et2O/toluene, 20 °C Ti

Ti(Me2N)3P P(NMe2)3

NMe2Cl

Cl NMe2(132)

2 Ti(NMe2)3Cl

2 Ti(NMe2)4

Ti

Ti(Me2N)3P P(NMe2)3

ClCl

Cl Cl(133)

TiCl2(NMe2)2 + H2C P(NMe2)3N

toluene, 20 °C

Scheme 61

(133) + ArCHO •

Ar

ArTHF, 25 °C, <5 min

Ar = p-MeC6H4, p-MeOC6H4

(27)

0\2!Dizirconiacyclobutane containing exocyclic ylide functions has been synthesized fromðMe2CCH1Ł3Zr and excess H1CPMe2 ð72OM043Ł[

Tin! and lead!substituted ylides are available from methylenephosphoranes and stannyl or plum!byl chlorides via transylidation reactions "cf[ Section 5[11[0[3[3# ð66CB566Ł[

5[11[0[4 Tetracoordinate Arsenic\ Antimony and Bismuth Derivatives

In comparison with the phosphonium ylides "X0X1CPY2# relatively little information is availableregarding the synthesis of C\C!diheterosubstituted arsonium\ stibonium and bismuthonium ylides"X0X1CEY2# ðB!69MI 511!90\ 71AOC"19#004\ 71COMC!I"1#570\ 76CSR34Ł[ The size di}erence between car!bon and arsenic\ antimony and bismuth atoms leads to relatively ine.cient ppÐdp overlap betweenthe C!sp1 orbitals and the large and more di}use d!orbitals of the heteroatom "E#\ and to decreasedelectrostatic interaction across the ylide P¦

0E− bond[ Consequently\ arsonium\ and especiallystibonium and bismuthonium ylides\ are in general more dipolar than their phosphorus analogsand have a tendency to decompose both in solution and in the solid state unless there is electronicstabilization[ A signi_cant increase in stability of the ylides X0X1CEY2 is observed\ however\ ifelectron withdrawing groups "X0\ X1# are conjugated with the ylidic carbon atom[ For example\bis"arenesulfonyl#!substituted arsonium ylides are thermodynamically stable at ambient temperatureand may be kept in air without signi_cant decomposition[ Stibonium ylides need anhydrous con!ditions and are frequently not isolated but used in situ[ Bismuthonium ylides are the most unstableof all Group 4B ylides[

The methods available for the synthesis of arsonium\ stibonium and bismuthonium ylides arenearly all analogous to methods used for the corresponding phosphonium ylides[

5[11[0[4[0 C\C!Diheterosubstituted arsonium ylides\ X1C1AsY2

Among the above ylides the only well characterized and studied compounds arebis"arenesulfonyl#methylenetriarylarsoranes[ The most simple synthesis of these compounds is based


on the reaction of dichloroarsoranes with compounds having acidic methylene groups\ _rst inves!tigated by Horner and Oediger in the late 0849s ð47CB326\ 48LA"516#031Ł[ For example\ "PhSO1#1CAsPh2 is prepared in 38) yield by heating bis"benzenesulfonyl#methane with Ph2AsCl1 in benzenein the presence of triethylamine[ The strong stabilizing in~uence of the PhSO1 groups upon theC1As bond is clearly indicated by the remarkable stability of the triphenylarsoniumbis"benzenesulfonyl#methylide towards oxygen and water over a period of days[ The structure ofthis ylide was con_rmed by x!ray crystallography ð77JCS"P1#0718Ł[

Variants of the above method include reaction of "ArSO1#1CH1 with triphenylarsine oxide inre~uxing acetic anhydride ð62T0586Ł[ The reaction presumably proceeds with initial formation of anacetoxyarsonium cation ðPh2AsOAcŁ¦[ This then reacts with a carbanion ð"ArSO1#1CHŁ− to forman arsonium salt which is readily converted into an ylide by loss of a proton[ The method is limitedto the preparation of highly stabilized arsonium ylides since it is necessary that the methylenereactant should be a fairly strong carbon acid[ Almost all examples of this approach have utilizedtriphenyl substituted arsenic derivatives[

Silyl substituted arsonium ylides can be prepared by the salt method based on the reaction of anarsonium salt\ usually obtained from a functionalized alkyl halide and an arsine\ with a suitablebase[ Thus triphenylarsonium trimethylsilylmethylide\ TMSCHAsPh2\ has been prepared in goodyield by treatment of the corresponding a!trimethylsilyl substituted onium salt with butyllithium inethyl ether ð54IC0347Ł[ The compound is also available from the reaction of the simple ylideH1CAsPPh2 with chlorotrimethylsilane followed by dehydrochlorination of the so formed arsoniumsalt with phenyllithium ð73TL3314Ł[ The ylide TMSCHAsPh2 readily undergoes desilylation bytrimethylsilanol ð57IC057Ł[ Similar reaction of the ylide with TMSOGeMe2 leads to a monogermylsubstituted arsonium ylide which disproportionates in solution to give "Me2Ge#1CAsPh2 "61)#ð66CB566Ł[

The interaction of quaternary arsonium salt "023# with NaNH1 in liquid ammonia occurs asoutlined in Scheme 51 to give ylide "024#[ Treatment of the latter with Ph1AsCl a}ordsdiarsenylmethylenearsorane "025# as the product of a transylidation reaction ð74OM233\ 76CB0170Ł[

(134)

Ph2AsCl

benzene, 75 °C94%

AsMePh2

Ph2As

Ph2AsAsMePh2

Ph2As

(135)

Ph2As AsMePh2

(136)

+

I–NaNH2

Scheme 62

Another method for the synthesis of bis"arenesulfonyl#methylenearsoranes consists of thermaldecomposition of diazo compounds in the presence of an arsine "Equation "17##[ The initial meth!odology consisted of heating a mixture of the diazo compound with an excess of the trapping agent\without solvent\ above the decomposition point of the diazo compound[ Subsequent improvementincludes the use of bis"hexa~uoroacetylacetonato#copper\ Cu"hfacac#1\ as a homogeneous catalystð71T2244\ 77S208Ł[

Ar = Ph, 4-MeC6H4

(28)(ArSO2)2CN2 + Ph3AsCu(hfa)2

benzene, reflux58–69%

AsPPh3

ArO2S

ArO2S

Related to the conversion of diazo compounds into arsonium ylides is the formation of arsoniumylides by thermal or photolytical decomposition of iodonium ylides[ For example\ by analogy withthe synthesis of phosphonium ylides shown in Equation "06#\ arsonium ylides can be obtained fromphenyliodonium bis"arenesulfonyl#methylides and triphenylarsine in yields of 48Ð61) ð77S802Ł[

5[11[0[4[1 Stibonium and bismuthonium ylides bearing heterosubstituents\ X1C1EY2 "E�Sb or Bi#

Isolable examples of the above compounds\ with the exception of bis"arenesulfonyl#!substitutedylides\ are virtually unknown[ The likely reason is their low stability[ Use of copper hexa!~uoroacetylacetonate as a catalyst has enabled the ylides "ArSO1#1CSbPh2\ Ar�Ph "67)# and3!MeC5H3 "66)# to be obtained from triphenyl!antimony and the diazo compounds "ArSO1#1CN1

in boiling benzene ð75T2776Ł[ These stibonium ylides are stable for long periods if kept in a dryatmosphere but in solution they are readily hydrolysed if any moisture is present[ Being dipolar

698Metalloid

molecules the ylides are insoluble in alkanes and ether[ Attempts to prepare stibonium ylides fromdichlorotriphenylantimony always led to ylides contaminated with "Ph2SbCl#1O ð77JCS"P1#0718Ł[

The bismuthonium ylide "PhSO1#1CBiPh2 has been made by the same method ð77S208Ł[ Althoughreasonably stable as a solid it decomposed rapidly in solution and hence could not be puri_edð77S208Ł[ It was also reported that this ylide can be generated by interaction of "PhSO1#1CHNa withPh2BiCl1 or Ph2BiO "89BCJ849#[ It should be noted here that stibonium and bismuthonium ylideshave speci_c chemical properties which little resemble those of phosphonium ylides[ Thus they donot take part in Wittig reactions\ even with very reactive aldehydes ð75T2776\ 77JCS"P1#0718Ł[

5[11[1 FUNCTIONS CONTAINING A DOUBLY BONDED METALLOID

5[11[1[0 Tricoordinate Silicon and Germanium Derivatives

Despite the intense activity on multiply bonded silicon and germanium species ð74CRV308\B!78MI 511!91\ 89CRV172\ 89JOM"399#010\ 83CCR316Ł there is little information on C\C!dihetero!substituted functions X0X1C1EY1 "E�Si or Ge#[ Among the latter only disilicon!substituted "X0\X1�R2Si# silaethenes have been studied in considerable detail by Wiberg and co!workersð73JOM"162#030Ł over the past two decades[ The most successful method for the generation of thesecompounds involves 0\1!elimination from a!lithiated silanes carrying a good leaving group on thesilicon atom[

5[11[1[0[0 Disilylsubstituted silaethenes\ "R2Si#1C1SiY1

A synthetic approach to disilylsubstituted silaethenes is shown in Scheme 52[ Generally\ the 0\1!elimination of LiY from the silanes "026# is reversible[ With poor leaving groups\ such as Y�MeOor PhO\ the equilibrium disfavors the silaethene[ In the case of good leaving groups\ such as Hal\ArSO1 or "PhO#1PO1\ the equilibrium lies to the right ð73JOM"162#030\ 78CB398Ł[ The rate of elim!ination of LiY from "026# in ether obeys _rst!order kinetics and increases for substituent Y in thesequence Ph1PO1³F³SPh³Ph1PO3³I³Br³Cl³p!MeC5H3SO2 ð70CB2494Ł[ The solvent alsohas an important in~uence on the results of these reactions[ In general\ the silaethenes tend to beformed as intermediates in ether solutions\ while in tetrahydrofuran they are not[ In a less basicsolvent such as pentane\ silaethene formation would be favored even more\ but the lithiation stepthen proceeds too slowly[ Thus\ a solvent of intermediate basicity like diethyl ether is the bestcompromise medium for the formation of silaethenes[

(137) (138)

–LiY

+LiY

SiTMS

TMSRLi

R

RSi

Li

TMS R

Y

TMS RSiBr

TMS R

Y

TMS R

Scheme 63

R = Me, But, Ph

Thermal elimination of ~uorotrimethylsilane represents an alternative to the elimination reactionsin solution[ For example\ the silaethene "TMS#1C1SiPh1 can also be generated by the vapor phasepyrolysis of "TMS#2CSiFPh1 ð79JOM"075#298Ł[

Silaethenes "027# are unstable even at −67>C and their existence was demonstrated by charac!teristic trapping experiments ð76CB0594Ł as well as by the formation of remarkably stable adductswith Lewis bases such as trimethylamine ð75JOM"204#8Ł\ N!"trimethylsilyl#benzophenone imineð76ZN"B#0944\ 76ZN"B#0951Ł and benzophenone ð77ZN"B#0357Ł "Table 2#[ In the absence of trappingreagents\ the formation of dimers or rearrangement products was observed ð70CB1976\ 70CB2494\70CB2407Ł[ Note that some of the derivatives of "027# obtained by cycloaddition of unsaturatedcompounds\ for example\ N!"trimethylsilyl#benzophenone imine\ can be used as a {store| for sila!ethenes "027# since they decompose easily to the starting materials by thermal cycloreversionð80CB0870Ł[

An increase in the bulkiness of one of the substituents through the use of a TBDMS group led toan isolable silaethene "039# ð72AG"E#0994Ł[ Transformation of ð"TMS#1CLi0SiFBut

1 = 3THFŁ "028#into "039# proceeds in diethyl ether in the presence of chlorotrimethylsilane at room temperatureand leads to a monotetrahydrofuran adduct of "039# "34)# ð72AG"E#0994Ł[ Pure crystalline silaetheneis obtained from the adduct by removing THF by azeotropic distillation with benzene[ It is kinetically


Table 2 Generation and trapping of transient silaethenes R0"TMS#C1SiR11 "027#[

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐSilaethene Precursor Trappin` rea`ent or detected product Ref[R0 R1

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐTMS Me "TMS#1"Me1YSi#CLi Y�Ph1PO1\ 1\2!dimethylbutadiene\ TMSN1 66AG"E#217

Ph1PO2\ Ph1PO3\ p!MeC5H3SO2 NTMS and TMSN2^ dimerTMS Me "TMS#2CSiMe1Y Y�Cl\ Br\ I MeOH:MeONa 67JOM"046#C49\

79JOM"080#244TMS Ph "TMS#2CSiPh1Y Y�Cl\ Br\ I MeOH:MeONa 79JOM"080#244TMS Me "TMS#1"Me1YSi#CLi Y�F\ Cl\ 1\2!dimethylbutadiene^ dimer 70CB1976\ 70CB2494

Br\ I\ PhS\ p!MeC5H3SO2\ MeSO2\Ph1PO1\ Ph1PO2\ Ph1PO3

TMS Me "TMS#1"Me1YSi#CLi Y�"PhO#1PO1 TMS!OMe\ TMS!Cl\ TMSN1 70CB2407NTMS\ RN2\ N1O\ Ph1CO\PhCN\ Ph1C�NTMS\ butadiene\isoprene\ 1\2!dimethyl!butadieneand isobutene

TMS Ph "TMS#2CSiPh1F rearrangement products 79JOM"075#298MeBut

1Si Me "MeBut1Si#"TMS#"Me1FSi#CLi 0\2!butadiene 75CB0344

TMS Me Adduct of silaethene with Me2N ButN2\ Ph1CNTMS\ acetone\ 75JOM"204#8isobutene

TMS Me "TMS#1"Me1YSi#CLi Y�F\ Br\ benzophenone 77ZN"B#0357Ph1PO3

TMS Me "TMS#1"Me1YSi#CLi Y�F\ Br Ph1C1NTMS 76ZN"B#0944\76ZN"B#0951

TMS Me adduct of silaethene with organic dienes and trans!piperylene 75CB2387\ 75CB0594\Ph1CNTMS 80CB0870

TMS Ph "TMS#1"Ph1YSi#CLi Y�H\ Hal\ RLi\ Ph1CNTMS\ 1\2! 78CB398OMe\ OPh\ Bu\ Ph dimethylbutadiene

*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ

stable at ambient temperature and decomposes slowly at 59>C[ The 0H and 02C NMR spectra ofthe silaethene "039# indicate a rapid intramolecular methyl exchange "Scheme 53# ð74AG"E#118\75CB0356Ł[ X!ray!structure determinations are now available for free silaethene "039# ð74AG"E#118\76OM21Ł\ its donor adducts with THF ð73JOM"160#270Ł\ and ~uoride anion "as its Li"01!crown!3#1Ł¦

salt# ð76OM24Ł[

SiTMS

TMS But

ButSi

Li

TMS But

F

TMS But Li

Cl TMS

F

SiMeBut

2Si

TMS Me

Me

(140b) (140a)(140)

SiMeBut

2Si

TMS Me

Me

SiMe

Me TMS

SiBut2Me

TMS-Cl

ether, RT

TMS

TMS

SiBut2

–LiCl, –TMS-F

Scheme 64

(140)

(139)

5[11[1[0[1 C\C!Diheterosubstituted germaethenes\ X1C1GeY1

The formation of transient germaethene "030# was postulated in the reaction of chloro!diphenylðtris"trimethylsilyl#methylŁgermane with cesium ~uoride ð72IZV848Ł[ It can be speculated

600Metalloid

that the precursor of "031# is the germaethene "030#\ which loses a TMS group to give a secondunstable germaethene followed by cyclodimerization to give "031# "Scheme 54#[

GeTMS

TMS

TMS

Ph

Cl

Ph GePh2

TMS

TMS

GePh2

TMS

Ph2Ge

GePh2

TMS

TMS

Scheme 65

CsF

–TMS-Cl

(141) (142)

A more established process for the generation of germaethenes is based on the formation of theC1Ge double bond by the salt elimination method "Scheme 55# ð75CB1855Ł[ For example\ thermaldecomposition of germyldisilylmethanes "032# in diethyl ether at −009>C to 099>C "depending onX# leads to transient germaethene "033#[ The latter has been identi_ed by its chemical reactivity]both by insertion into the O0H bond of alcohols ð75CB1879Ł and by ene reactions ð75CB1855\76CB0192Ł[ Various cycloaddition reactions have also been observed] ð1¦1Ł cycloadditions areobtained with the C1C bond of CH11CHOMe and the C1O bond of ketones ð75CB1879Ł\ ð1¦2Łcycloadducts are obtained with azides and N1O4 ð76CB0192Ł\ and ð1¦3Ł cycloadducts with dienesð75CB1879\ 76CB0192Ł[ The unwanted side reactions can be reduced by adding a su.cient excess oftrapping agent\ by the slow generation of the germaethene\ and by increasing the reaction tempera!ture[ If no trapping agents are added during the elimination of LiX from "032# the formation of{head to tail dimer| is observed[ Under special conditions "high temperatures or reactive substituents#germaethenes also stabilize themselves by rearrangement ð73JOM"162#030Ł[ By comparison with thesilaethene "TMS#1C1SiMe1 the Lewis acidity of germaethene "033# is weaker and its double bondis less polar ð75CB1879Ł[

GeMe2

TMS

TMS

Scheme 66

GeBr

TMS

TMS

Me

X

MeMe2Ge

GeMe2

TMS

TMS

TMS

TMSGe

Li

TMS

TMS

Me

X

Me2RLi

RBr2 2

(143) (144)X = F, Br, OMe, OPh, OC6F5, SPh, Ph2PO4, Ph2PO2

So far\ evidence for a stable C\C!diheterosubstituted germaethene is scarce[ The only isolatedcompounds with three heteroatoms attached to sp1!hybridized carbon are germaethenes "037# and"038# obtained by the reaction between the electrophilic cryptocarbene "034# and the stable ger!mylenes "035# and "036# "Scheme 56# ð76AG"E#687\ 76PAC0900Ł[

B

B

But

But

TMS

TMS

B

B

But

But

TMS

TMSGe

N(TMS)2

N(TMS)2

B

B

But

But

TMS

TMSGe

NSiMe2

N

But

But

NSiMe2

N:Ge

But

But

(148) + HClB

B

But

But

TMS

TMS

: (148)

Ge

N(TMS)2

N(TMS)2

(149)

:Ge[N(TMS)2]2(146)

(147)

(150)

Cl

(145)

Scheme 67


The yellow crystals "037# and "038# very slowly decolorize on exposure to air and melt withoutdecomposition[ The presence of the C1Ge double bond in "037# has been con_rmed by x!raydi}raction[ Germaethene "037# adds HCl with quantitative formation of the 0\2!diboretane "049#[

5[11[1[1 Functions Incorporating a Doubly Bonded Boron

Like the silaethenes and the germaethenes\ compounds with a C1B double bond are stable onlywhen they are sterically shielded by large substituents[ In addition\ electronic stabilization of theelectron!de_cient boron center is necessary either through pÐp delocalization "classical methylene!boranes "040#\ or borataallenes "041# or through sÐp interaction of the neighboring C0X bondswith the dicoordinate boron atom "nonclassical methyleneboranes with the three!center\ two!electron 2c!1e bonds\ "042## "Scheme 57# ð74MI 511!90\ 76MI 511!90\ 82AG"E#874Ł[

B

X

X

NR2 B

X

X

N

R

R

B

X

X

B

X

X R

R

B

R1

X

R2

R

R

(151)

(152)

(153)

+

–

B

X

–

R

R1

–

..

Scheme 68

A few standard and many unique reactions have been used to prepare compounds with a C1Bbond[ For reason of space\ emphasis will be placed on the preparatively important methods for thesynthesis of C\C!diheterosubstituted methyleneboranes[ Some C!monoheterosubstituted derivativesare described because their reactions are useful for the preparation of functionalized methylene!boranes[ There are also a number of specialized methods for the formation of a C1B bond which\however\ do not seem to have general applicability[ For further details a comprehensive reviewon this subject should be consulted ð82AG"E#874Ł[ It should also be noted that the reactivity ofmethyleneboranes resembles that of vinyl cations and also that of silaethenes[ The tricoordinatesilicon atom is related to the dicoordinate boron atom through the diagonal relationship in theperiodic system of elements ð89AG"E#390\ 89CB636Ł[

5[11[1[1[0 Methyleneboranes\ X1C1B0Y

"i# 0\1!Elimination reactions

C\C!Disilyl!substituted methyleneboranes can be synthesized by the elimination of ~uoro!trimethylsilane or methoxytrimethylsilane from tris"trimethylsilyl#methylboranes at temperaturebetween 369>C and 459>C "Equation "18##[ This method has proved successful for the preparationnot only of the amino"methylene#boranes "045# ð76CB0958Ł and "046# ð78CB484Ł but also the methyl!eneboranes "043# and "044# with methyl and t!butyl groups on the boron atoms ð78CB0946Ł[ Com!pounds "044#Ð"046# are remarkably stable\ whereas methyleneborane "043# rapidly dimerizes to thecorresponding 0\2!diboretane[ X!ray structural data is available for the compounds "044# ð78CB0946Łand "045# ð76CB0958Ł[

B

R

YTMS

TMS

TMS B

TMS

TMS

R450–560 °C

–TMS-Y

Y = F, MeO (154)(155)(156)(157)

R = Me, 73%R = But, 54%R = Pri

2N, 67%R = 2,2,6,6-tetramethylpiperidino

(29)

602Metalloid

Attempts to prepare the halo"methylene#boranes "047# via elimination of TMSOMe from"TMS#2CB"OMe#Hal resulted in the rearrangement products "059# "Scheme 58# ð89CB636Ł[ Theauthors supposed that the anticipated compounds "047# underwent a double ð0\2Ł shift of the Meand Hal groups\ via the intermediates "048#[ The boranes "059a\b# cyclodimerize at the B1C bondat 14>C and 58>C\ respectively[ Benzophenone reacts easily with "059# to produce the cyclic 0\1!oxaboretanes ð89CB636Ł[

B

OMe

HalTMS

TMS

TMS B

TMS

TMS

Hal540 °C

B

Me2Si

TMS Me

Hal

B

Me2Si

TMS

Me

Hal

(158) (159) (160a)(160b)

Hal = ClHal = Br

Scheme 69

"ii# Cycloreversion reactions

The thermal cycloreversion of 0!bora!1\3!cyclohexadienes ð74AG"E#0954Ł\ 0\2!diboretanesð78AG"E#673Ł and 0\1!dihydroboretes ð89AG"E#390Ł is of considerable potential for the generation ofmethyleneboranes[ For example\ upon melting "037>C and 066>C\ respectively# 0\2!diboretanes"050a\b# furnish the readily volatile methyleneboranes "051a\b#\ which can be separated by con!densation "yield ca[ 24)# from mixtures of predominantly higher boiling products "Equation "29##ð78AG"E#673Ł[ The bis"stannyl#methyleneborane "052b# has been detected by multinuclear NMRspectroscopy ð89AG"E#390Ł[

B

TMS

TMS

Ar∆

35–42%

(162a, b)

B

Me3Sn

Me3Sn

Ar+

(163a, b)

B

B SnMe3

SnMe3TMS

TMS

Ar

Ar(161a)(161b)

(30)

Ar = 2, 4, 6-Me3C6H2Ar = 2, 3, 5, 6-Me4C6H

The thermal cycloreversion of 0\1!dihydroborete "053# takes place at 019>C "reverse reaction tothe formation of "053##[ Distillation into CD1Cl1 cooled to −79>C a}orded a solution of "054#\which was investigated spectroscopically and trapped in a subsequent reaction step by 3!t!butyl!pyridine "Scheme 69# ð89AG"E#390Ł[

∆B

Me3Sn

Me3Sn

Ar

(165)

TMSTMS

B

TMS

Ar

TMS

Me3Sn

Me3Sn

(164)

N

But

100% (NMR)

B

Me3Sn

Me3Sn

N

Ar

But

Scheme 70

Ar = 2,3,5,6-Me4C6H

"iii# Miscellaneous reactions

Berndt and co!workers obtained the methyleneboranes "057# from an attempt to trap an inter!mediate in the reductive dimerization of diboranes "055# by addition of bis"trimethylsilyl#acetyleneð71JOM"123#C06\ 73ZN"B#0931\ 89AG"E#287Ł[ They found that the diboranes "055# themselves reactedwith the alkyne\ and 0\0!diborylalkenes "056# could be reduced by a sodium:potassium alloy


ð77AG"E#850Ł\ magnesium under ultrasonication ð77ZN"B#790Ł or Bogdanovic|!magnesium in diethylether ð89AG"E#287Ł to yield boriranylideneboranes "057# "Scheme 60#[

B B

Cl

RR

Cl TMS

TMS B

B

R

Cl

R

Cl

B

R

B RTMS

TMS B

BTMS

TMS

R

R

TMS TMS +2 e–

–2 Cl–

(166) (167) (168a–c)

Scheme 71

R = 2,3,5,6-Me4C6H (a), 2,4,6-Me3C6H2 (b), But (c)

Reaction of "057a# with mesityl"trimethylsilyl#acetylene results in the formation of ðboryl"silyl#methyleneŁborane "058#[ Similarly\ treatment of "057a# with bis"trimethylstannyl#acetylenea}ords ðboryl"stannyl#methyleneŁborane "069# "Scheme 61# ð82AG"E#874Ł[

Scheme 72

B

BTMS

TMS

R

R

Mes

(168a) Me3Sn SnMe3

TMSR B

TMS

B R

Mes

•

TMS

TMS

R B

Me3Sn

B R

Me3Sn

•

TMS

TMS

(169)

(170)

The C0C bond of the three!membered ring in the compounds "057# is reductively cleaved bylithium in ether to give the borataalkynes "060# ð77AG"E#850Ł[ These compounds can also be obtainedby reaction of the 0\0!diborylalkenes "056# with an excess of lithium in diethyl ether "Scheme 62#ð78AG"E#670Ł[ The interaction of the borylborataalkynes with electrophiles has provided a route toseveral new methyleneboranes[ Thus\ the reaction of "060# with Me2SnCl gave theðboryl"stannyl#methyleneŁborane "061# ð89ZN"B#189Ł[ The action of aryldi~uoroboranes\ RBF1\ on"060# resulted in formation of the stable "diborylmethylene#boranes "062# ð78AG"E#670Ł[ In the samefashion the borataalkynes "060# react with 0\0!diaryl!1\1!di~uorodiborane\ Dur1BBF1\ to form theorange!red B!boryl"0\2!diboretane!1!ylidene#boranes "063# ð80AG"E#483Ł[

B

BTMS

TMS

R

R

B

R

B R

TMS

TMSTMS

TMS B

B

R

Cl

R

Cl

B

B

Me3Sn

RTMS

TMS RB

B

R

R

B RTMS

TMS

B

B

R

R

B BDur2

TMS

TMS

2 Li

100% (NMR)

(171) (167)

4 Li

(168)

Scheme 73

(172) R = Mes (173) (174)

– –

R = 2,4,6-Me3C6H2 (Mes), 2,3,5,6-Me4C6H (Dur)

2Li+

604Metalloid

5[11[1[1[1 1!Borataallenes\ ðX1C1B1CY1Ł−

Among the methods which can be used to prepare 1!borataallenes the most important oneinvolves the thermal isomerization of C!borylboriranides ð81AG"E#0127Ł[ 1!Borataallene "066# isformed together with the 0\2!diboretanide "065# by heating "009>C\ 2 h# a toluene solution of theboriranide "064#[ In this reaction\ the C0C bond of the three!membered ring is cleaved\ and foreach product a di}erent duryl group migrates from a boron atom to the carbon atom locatedbetween the two boron atoms "Scheme 63# ð82AG"E#874Ł[

B

B

R

Dur

B

BTMS

TMS R

B

Dur

R

B

TMSTMS

Dur

[1,2]-Dur1

Dur1 B TMS

TMSB

R

[1,2]-Dur2 R = Ph

–Li+

Li+–

Dur2

Scheme 74

B TMS

TMS

+RLi–

Dur2

(177)

(175)

B

R

Dur1

(176)

(168)

Li+

..

∆

DurTMS

TMS

B

Dur2

B

Dur1

Ph

TMS

TMS

Dur

–

Dur = 2,3,5,6-Me4C6H

The 1!borataallenes "079# are accessible through thermal isomerization of 1!boryl!0\2!dibor!etanides "067# "Scheme 64#[ Presumably\ this reaction initially involves a ring!opening to give "068#\a process typical of 0\2!diboretanes[ Then\ one aryl group undergoes a ð0\2Ł migration from a tri!to the dicoordinate boron atom[ Compound "067# is accessible from the methyleneborane "062# andt!butyllithium "19)# ð89AG"E#0929Ł[

The high reactivity of the boronÐcarbon double bond in the methyleneboranes "051# has also

B

B

R

R(173)

BTMS

TMSR

B

B

R

R(178)

BTMS

TMS

But

RLi+

–ButLi 220 °C

70%B

B

B

But

R

R

R TMS

TMS–

Li+

(180)

B

B

B

R TMS

TMS

R

But

R

–

Li+

(179)

Scheme 75

R = 2,3,5,6-tetramethylphenyl


been exploited in the synthesis of 1!borataallenes and 1\2!diboratabutadienes "Scheme 65#[ Themethyleneborane "051a# reacts with lithium in toluene at 14>C to give the 1\2!diboratabutadiene"071a#\ the symmetrical dimer of its radical anion "070a#[ Under the same conditions\ "051b# yieldsthe 1!borataallene "072b# "the unsymmetrical dimer of the radical anion "070b## as major product"45)# together with "071b# as minor product "05)# ð89AG"E#0929Ł[

B

TMS

TMS

Ar

B

TMS

TMS

Ar B

TMS

TMS

R2

R1

R1

B

B

Ar

Ar

TMS

TMS

TMS

TMS

2Li+–

–

(182a, b)

B

Ar

TMS

TMS

B

TMS

TMS

.–

Li

(162a, b)

Li+

R1 = H, R2 = MeR1 = R2 = Me

(181a)(181b)

– –

2Li+

(183b)

Ar = 2, 4, 6-Me3C6H2 (a); 2, 3, 5, 6-Me4C6H (b)

Scheme 76

The reactions of 1!borataallenes with electrophiles have been used as a method for preparationof a few types of heterosubstituted methyleneboranes\ including C\C!diboryl derivatives[ For exam!ple\ 0\0!diboryl!1!borataallenes "079# can be protonated with cyclopentadiene to give the"diborylmethylene#boranes[ In all cases the electrophiles attack the carbon atom bonded to the twotrimethylsilyl groups regioselectively\ with the result that only "diborylmethylene#boranes and notthe isomeric "disilylmethylene#boranes result ð82AG"E#874Ł[

5[11[2 FUNCTIONS INCORPORATING A DOUBLY BONDED METAL

5[11[2[0 Transition Metal Carbene Complexes

For the purpose of this survey\ transition metal C\C!diheterosubstituted carbene complexes willbe de_ned as the species of the formula X0X1C1MLn which formally contain a double bond betweencarbon and the transition metal[ Systematic "IUPAC# nomenclature for these compounds uses thesu.x {ylidene|\ the ligand being regarded as neutral with respect to the metal oxidation state^ thusthe complex ð"OC#4Cr1C"OMe#ClŁ is called pentacarbonylðchloro"methoxy#methylideneŁchromium"9#\ but trivially is chloro"methoxy#carbenepentacarbonylchromium"9#[

Complexes containing heterosubstituted carbene ligand were _rst prepared by Fischer in the0859s ð53AG"E#479\ 65AOC"03#0Ł[ Since then this _eld has experienced explosive growth and continuesto expand at a rapid rate ð61CRV434\ 62CSR88\ 79MI 511!90\ 78CRV0692Ł[ A large number of methodshave been developed\ providing access to a great variety of carbene complexes involving nearly allthe transition metals[ Various aspects of this chemistry have been reviewed extensively in recent yearsð75AOC"14#010\ 77CRV0182\ 80SL270\ 80CSR492Ł[ Therefore\ only most important synthetic examples willbe selected here from the abundance of material available ðB!73MI 511!90\ 78MI 511!92Ł[

606Metal

5[11[2[0[0 Dihalocarbene complexes\ Hal1C1MLn

The _rst transition metal dihalocarbene complex of the type Hal1C1MLn was prepared in 0866by reaction of tetraphenylporphyrinoiron"II#\ ð"TPP#FeIIŁ\ with CCl3 in the presence of excess ironpowder ð66CC537\ 77CSR0010Ł[ In 0867 the di~uorocarbene complex of molybdenum\ ð"h4!C4H4#"CO#2Mo1CF1Ł¦\ was detected in solution by 08F and 02C NMR spectroscopy ð67JOM"042#56Ł[ In0879 a stable dichlorocarbene complex of osmium"I# was described ð79JA0195Ł and since then alarge number of dihalocarbene complexes has been prepared and thoroughly characterized ð72MI511!90Ł[ The review by Brothers and Roper ð77CRV0182Ł provides a valuable survey of the literatureup to 0876[

Several synthetic routes to Hal1C1MLn species have been developed\ but each one is appropriatefor only a limited number of transition metal substrates[ The most general method for the prep!aration of the dihalocarbene complexes starts from metal trihalomethyl derivatives\ Hal2C0MLn[

"i# Synthesis from trihalomethyl complexes

The chemistry of tri~uoromethyl derivatives of the transition metals has been the focus of muchattention ð82AOC"24#100Ł[ As a result\ many transition metal tri~uoromethyl species are known\ andthese o}er the possibility of modi_cation of the CF2 ligand to form Hal1C1MLn carbene complexes[In principle an electrophilic attack on coordinated CF2 ligand using H¦\ TMS¦\ BF2 or SbF4

as ~uoride anion abstracting agents lead to di~uorocarbene complexes "Scheme 66#[ Thus\ theruthenium"II# complex "073#\ when treated with anhydrous HCl or TMS!Cl as ~uoride abstractingreagents forms the di~uorocarbene product "074# "Scheme 67# ð71JOM"123#C8Ł[ The attack of SbF4

on the CF2 group in CpMo"CF2#"CO#2 generates the cationic di~uorocarbene complexðF1C1Mo"Cp#"CO#2ŁSbF5 ð67JOM"042#56Ł[ Likewise\ ðF1C1Mn"CO#4ŁBF3 is obtained fromMn"CO#4"CF2# and BF2 ð74OM0729Ł[

F3C MLn–F–

MLn

F

F +

–LMLn-1

F

F

Scheme 77

L

Ru

LCF3

ClMeCN

Cl

L

Ru

LCF2

ClMeCN

OC

HCl or TMS-Cl

benzene, RT

+

Cl–

L

Ru

LCF2

ClCl

OC

(184) (185)L = PPh3

Scheme 78

Reaction of tri~uoromethyl complexes with BHal2 "Hal�Cl\ Br\ I# converts F2CMLn toHal2CMLn[ The use of excess BHal2 resulted in both halide exchange and stabilization of the cationicdihalocarbene complexes[ For example\ treatment of "075# with excess BCl2 produced the stabledichlorocarbene complex "076# which was fully characterized\ including an x!ray crystal structurestudy[ An analogous reaction was successfully used in the preparation of dibromocarbene complex"077# "Equation "20## ð73OM203\ 74OM0729\ 77CRV0182Ł[ Tri~uoromethyl species ðF2C"Cp#Fe"CO#"PPh2#Ł ð74OM0729Ł and ðF2C"Cl#Ru"CO#1"PPh2#1Ł ð75AOC"14#010Ł also react with BCl2 to givedichlorocarbene complexes[

CpFe(CF3)(CO)2 BHal4–Fe(Cp)(CO)2

Hal

Hal +2BHal3

benzene, RT(31)

(186) (187)(188)

Hal = ClHal = Br

"ii# From reactions with Cd"CF2#1 and H`"CCl2#1

Roper and co!workers found that the highly reactive complex ðCd"CF2#1 =GLYMEŁ ð75IS41Łcan be used for CF1 transfer to a suitable metal substrate ð75AOC"14#010Ł[ A good example of


this method is the synthesis of di~uorocarbene ruthenium and osmium complexes "078# "Equa!tion "21## ð75JOM"299#056\ 72CC608Ł[ The oxidative addition product F2CRu"CdCF2#"CO#1"PPh2#1is a likely intermediate in this reaction[ Other zerovalent ruthenium and osmium complexes\RuCl"NO#"PPh2#1\ OsCl"NO#"PPh2#2 and Os"CO#"CS#"PPh2#2\ react similarly\ giving F1C1MCl"NO#"PPh2#1 "M�Ru\ Os# and F1C1Os"CO#"CS#"PPh2#1\ respectively ð77CRV0182Ł[

(32)M(CO)2(PPh3)3 M(CO)2(PPh3)2

F

FCd(CF3)2•GLYME

(189) M = Ru, Os

The cadmium reagent was also successfully used for CF1 transfer to a d7 iridium center[ Anexample is the preparation of the di~uorocarbene complex F1C1Ir"I#"CO#"PPh2#1 from IrI"CO#"PPh2#1[ At higher temperatures\ reaction of ðCd"CF2#1 = glymeŁ with Vaska|s complex or withF2CIr"CO#"PPh2#1 results in transfer of a CF1 group and also\ for the former substrate\ replacementof chloride with CF2 "Equation "22## ð77CRV0182Ł[

(33)IrCl(CO)(PPh3)3 Ir(CF3)(CO)(PPh3)2

F

FCd(CF3)2•GLYME

The mercury compound Hg"CF2#1 oxidatively adds across one Hg0C bond to Ru"CO#1"PPh2#1producing the stable complex F2CRu"HgCF2#"CO#1"PPh2#1\ containing both F2C and F2CHg ligandsð71JOM"123#C8Ł[ However\ ruthenium ð71JOM"122#C48Ł\ osmium ð79JA0195Ł and iridiumð71JOM"125#C6Ł d5 complexes react with Hg"CCl2#1 to give the dichlorocarbene species "Equations"23# and "24##^ the probable explanation is that Cl2C0M derivatives are formed as intermediatesbut then lose a phosphine ligand\ HCCl2 and mercury[ The osmium and iridium complexes havebeen structurally characterized ð71JOM"125#C6Ł[

(34)MHCl(CO)(PPh3)3 MCl2(CO)(PPh3)2

Cl

ClHg(CCl3)2

toluene (reflux)80%M = Ru, Os

(35)IrHCl2(PPh3)3 IrCl3(PPh3)2

Cl

ClHg(CCl3)2

toluene (reflux)80%

"iii# Modi_cation of dichlorocarbene complexes

The displacement of chloride from a Cl1C ligand by other nucleophiles can\ in some cases\ beused for the preparation of new dihalocarbene complexes[ Thus\ by analogy with the conversion ofRCOBr to RCOF upon reaction with ðCd"CF2#1 = glymeŁ the reaction of the osmium complex "089#with the cadmium reagent includes exchange of a chloro for a ~uoro substituent in a metalcoordination sphere "Equation "25## ð73JOM"158#C44Ł[ The use of AgClO3ÐMeCN to abstract a labilechloride from a carbene complex\ with concomitant coordination of acetonitrile or CO\ is a usefulroute to several ruthenium and osmium cationic complexes "Structures "080#Ð"082#^ Equation "26##ð73JOM"158#C44\ 77CRV0182Ł[

(36)Os(CO)(PPh3)2

Cl

FCd(CF3)2•GLYME

MeCN, RTOs(CO)(PPh3)2

Cl

Cl

(190)

(37)MCl(MeCN)(CE)(PPh3)2

Cl

FAgClO4/MeCN

MCl2(CE)(PPh3)2

Cl

Cl +

ClO4–

(191)(192)(193)

M = Ru, E = OM = Os, E = OM = Os, E = S

608Metal

5[11[2[0[1 Oxygen!\ sulfur! and nitrogen!substituted carbene complexes\ RE"X#C1MLn "E�O orS# and R1N"X#CMLn

Since very authoritative reviews of the O!\ S! and N!substituted transition metal carbene com!plexes exist ð79MI 511!90\ B!73MI 511!90\ 80SL270Ł only a brief survey of some of the more generalsynthetic approaches will be provided here[ Basically\ three strategies are used for the preparationof the title compounds] "i# modi_cation of a coordinated "noncarbene# carbon ligand\ "ii# modi!_cation of a carbene or carbyne ligand coordinated to a metal\ "iii# reactions of transition metalcomplexes with organic carbene precursors[ The various types of synthesis have di}ered widely andit will be convenient to deal with each separately[

"i# From lithium acyl metallates

The route from lithium acyl metallates is the most useful and general approach to the preparationof oxygen!substituted carbene complexes from noncarbene precursors[ In this method a carbonylligand is converted into an alkoxy! or aryloxycarbene ligand by successive addition of a nucleophile"083# and an electrophile "Scheme 68# ð65AOC"03#0\ B!73MI 511!90Ł[ Various metal carbonyls havebeen used as precursors to carbene complexes\ including W"CO#5\ Cr"CO#5\ Mo"CO#5\ Mn1"CO#09\Tc1"CO#09\ Re1"CO#09\ Fe"CO#4 and Ni"CO#3[ These compounds are arranged in order of decreasingstability of the carbene product ð79MI 511!90Ł[

M(CO)m–1Ln–O

Nu

(194)

Nu– R+

(OC)mMLn M(CO)m–1Ln

RO

Nu

Scheme 79

Alkoxycarbene complexes are normally synthesized by the original Fischer procedure\ involvingthe reaction of an organolithium reagent with a metal carbonyl\ followed by alkylation of theresulting {ate| complex[ Alkylation can be performed with oxonium salts ð58CB0384Ł\ methyl ~uoro!sulfonate ð62SRI138Ł or methyl tri~ate ð89TL1418Ł[ More recently it was shown that the use of phasetransfer conditions su.ciently activate the acyl metallate to allow alkylation by readily accessiblealkyl halides[ The procedure is preparatively useful for accessing chromium containing carbenes\ butyields of the analogous molybdenum and tungsten containing species are only ³09) ð82OM1795Ł[Chlorosilanes have been used to generate silyloxycarbene complexes ð66CB1463\ 57JOM"01#P0Ł[ A widerange of other heterosubstituted carbene complexes has been synthesized via the metal carbonylroute ðB!73MI 511!90\ 78MI 511!92Ł[ Selected examples are presented in Table 3[

"ii# Electrophilic addition to coordinated acyl\ thioacyl and imidoyl li`ands

Alkylation of anionic acyl metallate is the second step in the classic Fischer synthesis of carbenecomplexes[ A related synthetic technique involves electrophilic addition to certain neutral acylcomplexes ð63JOM"79#C24\ 63JOM"70#C6\ 64BCJ2580\ 65JOM"001#116\ 67JOM"048#62Ł[ Selected reactions arepresented here to illustrate the scope of this type of transformation[

The adducts of alkoxy"dialkylamino#carbenes with Hg1¦ are synthesized by methylation ofbis"carbamoyl#mercury compounds with trimethyl! or triethyloxonium ~uoroborate "Equation "27##ð56AG"E#459Ł[ Thioacyl platinum complex reacts in a similar fashion "Equation "28## ð64IC0402Ł[ Theconversion of several acyl complexes into C\C!dioxygen!substituted cyclic carbene ligands has beenachieved by intramolecular alkylation reactions "Equations "39# and "30## ð63JCS"D#240\ 63JCS"D#0078\65JOM"002#C34Ł[

Hg(CONR2)2 {[MeO(R2N)C]2Hg}2+ 2BF4–

Me3O+ BF4–

CH2Cl2, RT(38)


Table 3 Selected examples illustrating the synthesis of diheterosubstituted metal carbene complexes viaacylmetallates[

Cr(CO)5

Et2N

EtO

Reaction

Cr(CO)5

N

EtO

Ref.Yield(%)

Ph

Ph

Cr(CO)6 20

(OC)5MoNMe

MeN

76JOM(118)C3370AG(E)309

Cr(CO)6 40

cis-(OC)4MoNMe

MeN

50

i, Et2NLi

ii, Et3O+BF4–

74JCS(D)1494

MeO

77JCS(D)1272

W(CO)4-cis

Me2P

EtO

W(CO)6 1.5 72CB2558

W(CO)6 W(CO)5

Ph3Si

EtO

Ph3SnCo(CO)4

77CB346776JOM(113)C31

15.4

Co(CO)3SnPh3

Cy2N

EtO

Cr(CO)6

88JOM(355)43775

Cr(CO)5

Mes2(H)Si

EtO

2

93JOM(459)5570

i, Ph2C=NLi

ii, Et3O+BF4–

i, MeLi

ii, MeOSO2F

i, Me2PLi

ii, Et3O+BF4–

i, Ph3SiLi

ii, Et3O+BF4–

i, Cy2NLi

ii, Et3O+BF4–

i, Mes2Si(H)Li

ii, Et3O+BF4–

MeSO3F

CH2Cl2, RT80%

S

trans-Cl(Ph3P)2Pt NMe2

trans- FSO3–Pt(PPh3)2Cl

MeS

MeS(39)

+

AgBF4

60%

Cl

O Mn(CO)5

OMn(CO)5

H

H

(40)BF4–

+

(41)HOCH2CH2Cl/Et3N

[OsCl(CO)2(CNR)(PPh3)2]+

O

OOsCl(CO)(CNR)(PPh3)2 Cl–

+

R = p-tolyl

Some dithiocarbene complexes can be obtained via h1!CS1 adducts of transition metals[ Anexample is alkylation of the osmium complex "084# with MeI "Equation "31## ð64JOM"89#C23Ł[ Cyclicdithio! and disilenocarbene ligands are formed when dihaloalkanes are used as the electrophilicreagents in these reactions "Equation "32## ð65JOM"096#C26Ł[

(OC)2(PPh3)2OsS

S

MeI

benzene, RTI(CO)2(PPh3)2Os

SMe

SMe

+

I– (42)

(195)

610Metal

(43)(OC)2(PPh3)2RuE

E

BrCH2CH2Br

Se

SeRuBr2(CO)(PPh3)2

E = S or Se

"iii# Nucleophilic addition to coordinated isocyanides

Coordinated isocyanides react with nucleophiles to yield carbene complexes[ Platinum"II# andpalladium"II# species have been most extensively investigated\ and the range of nucleophilic reagentsemployed in these reactions has included alcohols\ amines and thiols[ The typical examples areshown in Equations "33# and "34# ð58CC0211\ 60JCS"A#10\ 63JOM"70#C6Ł[ The method has been extendedto gold"I# ð62G262Ł\ mercury"II# ð58JOM"05#164\ 69JOM"14#144Ł\ iron"II# ð58CC312\ 69JOM"13#194\61JA306Ł\ nickel"II# ð63JCS"D#246Ł\ ruthenium"II# ð62JA3658\ 63IC810Ł and osmium"II# ð64JOM"80#C50Łcompounds[ Examples from more recent literature include preparation of chromium carbene com!plexes by reaction of coordinated trichloromethylisocyanide ð77AG"E#0233\ 78CB0896Ł and tri~uoro!methylisocyanide ð89CB640Ł with secondary amines and synthesis of neutral _ve!membered cyclicdiamino!\ aminothio!\ and aminooxycarbene derivatives of palladium"II# and platinum"II# startingfrom the isocyanide complexes cis!Cl1"PPh2#M"CNR# ð77IC1798Ł[

(44)RXH

40–90%PtBr2(PEt3)

MeHN

RX

(Et3P)Br2Pt(CNMe)

RXH = MeOH, PrnOH, PhNH2, BusNH2

(45)EtSH

[(MeNC)4Pt]2+ (PF6

–)2 Pt(CNMe)

MeHN

EtS

2

2+

2PF6–

"iv# From or`anic carbene precursors

A wide range of C\C!dinitrogen substituted carbene complexes has been synthesized via scissionof electron!rich alkenes ð79MI 511!90Ł[ The early works dealt with platinum complexes where thecarbene could be introduced via halogen!bridge cleavage or ligand displacement ð61CRV434\64JOM"099#028Ł[ The _rst carbene complex "085# prepared in this way is shown in Equation "35#ð60CC399Ł[ This reaction\ which is normally carried out in re~uxing xylene\ was generalized[ Othercarbene complexes have been obtained by this procedure including the complexes of chromium"9#ð66JCS"D#1059Ł\ molybdenum"9# ð66JCS"D#0161Ł\ tungsten"9# ð66JCS"D#0172Ł\ ruthenium"I# ð61CC816\66MI 511!90Ł\ iridium"I# ð63JCS"D#0716Ł\ osmium"II# ð67JCS"D#715\ 67JCS"D#726Ł\ and ruthenium"II#ð65CC533\ 66JCS"D#1061\ 67JCS"D#726\ 68JCS"D#0818Ł[

ClPt

ClPt

PEt3

ClEt3P

Cl N

N

N

N

Ph

Ph

Ph

Ph

+N

N

Ph

Ph

Pt PEt3

Cl

Cl

xylene (reflux)2 (46)

(196)

A related synthetic technique involves reactions of transition metal complexes with electron rich`em!dichlorides in which the C0Cl bonds have appreciable ionic character ð79MI 511!90Ł[ Twoexamples are shown in Equations "36# ð61CC740Ł and "37# ð64CC818Ł[ The procedure is signi_cant inthat it allows the preparation of carbene complexes in unusually high oxidation states ð63JCS"D#0480\67JCS"D#237Ł[ Imidazolium\ oxazolium and thiazolium salts have been used to obtain certain carbenecomplexes ð64JCS"D#828\ 75AOC"14#010Ł[ Although the products of these reactions are often di.cultto prepare by other methods\ this technique is of limited applicability[


(Ph3P)3RhCl + [(PhNH)2CCl]+ Cl–CHCl3, 20 °C

Rh(PPh3)2Cl3PhHN

PhHN

(47)

(48)(OC)5MnNa + (Me2NCCl2)+ Cl–LiClO4

THF, 20 °C24%

Mn(CO)5

Cl

Me2N

ClO4–

+

The homoleptic bis"carbene# adducts of silver"I# and copper"I# are available directly from thereaction of the stable nucleophilic carbene 0\2!dimesitylimidazol!1!ylidene and the correspondingmetal tri~ate ð82OM2394Ł[

"v# Syntheses involvin` functionalization of the carbene li`and

The nucleophilic substitution reactions at the carbene carbon have found wide application in themodi_cation of carbene ligands ð79MI 511!90\ B!73MI 511!90Ł[ The alkoxycarbene complexes\ whichare obtainable directly from the carbonylmetal compounds\ can be used as organometallic esterequivalents ð80SL270Ł[ Thiols\ primary and secondary amines\ and organolithium compounds reactby substituting for the alkoxy group\ leading to heteroatom!stabilized carbene complexes[ Reactionsnormally a}ord excellent yields\ and products are easily separated[ An example is the preparationof the carbene complex "086# by aminolysis of an alkoxycarbene substrate "Equation "38##ð65JOM"002#C20\ 66CB2356Ł[

Me2NH

ether, –78 °C89%

Cr(CO)5

Ph3Si

Me2N

Cr(CO)5

Ph3Si

EtO

(49)

(197)

Halide displacement from the dihalocarbene ligands by nitrogen\ oxygen and sulfur based nucleo!philes frequently leads to the formation of new heteroatom!substituted carbene complexes ð79MI511!90\ 77CRV0182Ł[Equations "49#Ð"41# illustrate the scope of this method[ Primary alkyl! and aryl!amines react with dihalocarbene complexes to give products containing isocyanide ligandsð71JOM"122#C48\ 71JOM"123#C8\ 73OM203\ 77JOM"227#282Ł[ The mechanism of isocyanide formation mayinvolve successive HCl loss from a Cl"RNH#C1MLn intermediate[ The reaction of the rutheniumcomplex ðCl1C1RuCl1"CO#"PPh2#1Ł with ethanolamine includes the formation of the isocyanidecomplex and its subsequent cyclization into an aminoalkoxycarbene complex ð71JOM"122#C48Ł[

Me2NHRuCl2(CO)(PPh3)2

Me2N

Cl

RuCl2(CO)(PPh3)2

Cl

Cl

(50)

RSH OsCl2(CO)(PPh3)2

RS

F

OsCl2(CO)(PPh3)2

Cl

F

(51)

IrCl3(PPh3)2IrCl3(PPh3)2

Cl

Cl S

S(52)

HSCH2CH2SH

"vi# Nucleophilic addition to carbyne complexes

Carbyne complexes can be converted into carbene complexes by the nucleophilic addition reac!tions ð66JOM"018#086Ł[ In some cases this route leads to transition metal carbenes that are inaccessibleby any of the other synthetic methods[ Two examples\ one resulting from nucleophilic addition to

612Metal

the carbyne complexes "087# ~uoride anion ð65AG"E#505Ł and the other resulting from addition oflithium thiocyanate ð66JOM"017#C38\ 67CB2431Ł\ are shown in Scheme 79[ Many related reactions havebeen described ð80AOC"21#116Ł[

[(OC)5Cr NR2]+ BF4–

Cr(CO)5

F

Et2N

Cr(CO)5

Et2N

SCN

Bun4N+F–

CH2Cl2/THF, –78 °C61%

LiSCN

CH2Cl2, 0 °C83%

(198)R = Me, Et

Scheme 80

"vii# Miscellaneous

Open chain Fischer type carbene complexes "CO#4Cr1C"OMe#CH1R0 react easily with N\N!dimethylformamideÐdialkyl acetal "dmfÐdaa#[ When R0�H\ the carbene complex "CO#4Cr1C"OMe#CH1CHNMe1 is formed in high yield^ however\ when R0�alkyl\ the reaction productsare dialkoxy complexes "CO#4Cr1C"OMe#OR1\ in which the OR1 group comes from the dmfÐdaað82OM1883Ł[ The latter reaction represents a new and general method for the synthesis of chromiumdialkoxycarbene complexes[

Various neutral and cationic gold"I# amino"thio#carbene complexes were obtained in satisfactoryyields on addition of lithiated 3!methylthiazole to gold"I# chloride compounds and subsequentprotonation or alkylation of the products formed ð89CC0611Ł[ Similarly\ the _rst monocarbenecomplex of copper"I# has recently been synthesized by alkylation of a thiazolyl cuprate"I#\ ðLinCuCl"dmt#mŁ "dmt�3\4!dimethylthiazolyl#\ with CF2SO2Me ð83AG"E#561Ł[

5[11[2[0[2 Silicon!substituted carbene complexes\ R2Si"X#C1MLn

The chemistry of silyl!substituted Fischer!type carbene complexes was reviewed by Schubertð77JOM"247#104Ł[ Compared with the rich chemistry of transition metal carbene complexes havingelectron!donating substituents at the carbene carbon center\ compounds R2Si"X#C1MLn have beeninvestigated only brie~y[ The alkoxy"silyl#carbene complexes R2Si"EtO#C1MLn "M�Cr\ Mo orW# can be prepared by standard methods from metal carbonyls and alkali!metal silyls\ followed byalkylation with EtO2

¦BF3− ð66CB2356\ 82JOM"348#44Ł[ Several alkylthio"silyl#carbene complexes were

obtained via the nucleophilic displacement of an alkoxy group from a complexed silyl!substitutedcarbene ligand ð75CB1899Ł[ For example\ Ph2Si"EtO#CW"CO#4 reacts with EtSH in the presence ofdisul_de "Et1S1# to give Ph2Si"EtS#CW"CO#4 in almost quantitative yield[

Reaction of alkoxy"silyl#carbene complexes with ammonia\ primary and secondary amines yieldsamino"silyl#carbene complexes if the amine is not too bulky ð75OM062\ 82JOM"348#44Ł[ With bulkyamines "e[g[\ HNPri

1\ HNCy1# no aminolysis takes place[ When the sterically demanding aminesHNEt1\ HNBunMe or HN"CH1Ph#Me are used\ monoalkylamino!substituted carbene complexesR2Si"AlkNH#CM"CO#4 are formed instead\ owing to cleavage of one of the N!alkyl substituentsð89JOM"274#110Ł[

Depending on the group X thermolysis of silyl!substituted carbene complexes R2Si"X#CM"CO#4results in fragmentation of the carbene ligand "X�OAlk or NHAlk#\ formation of stable 05!electron carbene complexes R2Si"Alk1N#CMLn\ or formation of ketenes Ph2Si"X#C1C1O "X�RO\RS# ð77JOM"244#132\ 78JOM"262#192\ 89JOM"274#110Ł[ The stabilities of the carbene complexesR2Si"Alk1N#CM"CO#3 decrease in the order W×Mo½Cr for a given R2Si group\ and in orderPh2Si×MePh1Si×Me1PhSi for a given metal ð77JOM"247#104Ł[


5[11[2[1 Functions With a Formal TinÐCarbon Double Bond

Isolable compounds of doubly bonded tin are very rare ð89CRV172\ 81OM1637Ł[ Up to 0884only two examples of the stable heterosubstituted stannaalkenes have been described[ The Berndtcompounds "088# were synthesized by the reaction between stannylenes and the cryptocarbene "034#"Equation "42## ð76AG"E#435Ł[ The structure of "088a# has been con_rmed by x!ray crystallography[

B

B

But

But

TMS

TMS B

B

But

But

TMS

TMSR2Sn

(145) (199a, b)

R2Sn + :

R2Sn = [(TMS)2CH]2Sn (a) or (b)N

SiN

Sn

But

But

Me

Me

(53)

The chemistry of stannaalkenes is not well developed\ and only the addition of HCl across thetinÐcarbon double bond has been performed[


6.23Tricoordinated StabilizedCations and Radicals, +CXYZand ·CXYZTHOMAS L. GILCHRISTUniversity of Liverpool, UK

5[12[0 CARBOCATIONS BEARING THREE HETEROATOM FUNCTIONS 614

5[12[0[0 Introduction 6155[12[0[1 Cations Bearin` Three Haloèns 6155[12[0[2 Cations Bearin` Haloèn and Chalcoèn Functions 6155[12[0[3 Cations Bearin` Haloèn\ Other Elements and "Possibly# Chalcoèn Functions 616

5[12[0[3[0 Cations bearin` two haloèns and one nitroèn function 6165[12[0[3[1 Cations bearin` two haloèns and one other heteroatom function 6165[12[0[3[2 Cations bearin` one haloèn\ one chalcoèn and one nitroèn function 6165[12[0[3[3 Cations bearin` one haloèn and two nitroèn functions 617

5[12[0[4 Cations Bearin` Three Chalcoèn Functions 6185[12[0[4[0 Three oxyèn functions 6185[12[0[4[1 Three sulfur functions 6185[12[0[4[2 Three selenium functions 618

5[12[0[5 Cations Bearin` Chalcoèn and Nitroèn Functions 6185[12[0[5[0 Two oxyèn and one nitroèn function 6185[12[0[5[1 Two sulfur and one nitroèn function 6295[12[0[5[2 Two selenium and one nitroèn function 6295[12[0[5[3 Two different chalcoèn and one nitroèn function 6295[12[0[5[4 One oxyèn and two nitroèn functions 6205[12[0[5[5 One sulfur and two nitroèn functions 6205[12[0[5[6 One selenium and two nitroèn functions 621

5[12[0[6 Cations Bearin` Chalcoèn\ Metal and "Possibly# Nitroèn Functions 6215[12[0[7 Cations Bearin` Three Nitroèn Functions 6215[12[0[8 Cations Bearin` Nitroèn and Other Element Functions 6225[12[0[09 Cations Bearin` Phosphorus and Silicon Functions 622

5[12[1 CARBON!CENTERED RADICALS BEARING THREE HETEROATOM FUNCTIONS 623

5[12[0 CARBOCATIONS BEARING THREE HETEROATOM FUNCTIONS

The aim of this chapter is to draw together the literature on the methods of preparation of saltsin which the positively charged component is\ at least formally\ a carbocation with three attachedheteroatom functions[ Many salts of this type are isolable and several methods of preparation havebeen discussed in earlier chapters of this volume[ The carbocations have been classi_ed accordingto the types of heteroatom attached to carbon[ This review also contains a brief discussion of

614

615 Tricoordinated Stabilized Cations and Radicals

carbon!centered radicals with three heteroatom functions[ None of these species is isolable but afew such radicals can be classi_ed as {persistent| ð65ACR02Ł[

5[12[0[0 Introduction

Tricoordinate carbocations are well established as reaction intermediates but special stabilizingfactors are necessary to permit salts containing such cations to be isolated[ Heteroatom substituentscan provide the necessary stabilization by electron donation from a lone pair into the vacant p!orbital on carbon[ Nitrogen is the most e}ective of the common heteroatoms at this type of electronpair donation\ to the extent that the presence of just one nitrogen substituent can enable salts of theformal carbocation to be isolated[ The structure of such a cation can be represented as a resonancehybrid of carbenium ion "0a# and iminium ion "0b# forms[ On the basis of x!ray crystal structuredata and spectroscopic evidence it is clear that the structures are much more accurately representedas the iminium ions "0b# containing a formal double bond\ and with the positive charge largelycentered on nitrogen[ When the formal carbocation bears more than one heteroatom substituentthere are further possibilities for charge delocalisation[

NR2

Y

X

NR2

Y

X++

(1a) carbenium ion (1b) iminium ion

This chapter includes examples of methods of preparation of salts in which the cations contain atricoordinate carbon atom with three attached heteroatoms[ The positive charge is delocalised\ to agreater or lesser extent\ over the heteroatom substituents and the bonds to the central carbon haveconsiderable p!bonding character[ The types of structure discussed include some species which arenot normally regarded as stabilized carbocations\ such as dichloroiminium cations and cationicmetal carbene complexes^ examples of these types are included to illustrate the range of possiblesubstituents[

5[12[0[1 Cations Bearing Three Halogens

The salts ¦CX2SbF4X− "X�Cl\ Br and I# have been generated at −67>C by reaction of theappropriate tetrahalides CX3 with antimony penta~uoride in SO1ClF ð78JA7919Ł[ The salts are stablein solution below −49>C and spectroscopic data were obtained[ The corresponding tri~uoromethylcation could not be generated in this way[ It has been suggested that the p!electron donor ability of~uorine is more than o}set by its electron!withdrawing inductive e}ect] calculations predict thatthe tri~uoromethyl cation should be less stable than the other trihalomethyl cations ð80CC864Ł[

5[12[0[2 Cations Bearing Halogen and Chalcogen Functions

There are few examples of isolable salts of this type[ The salt "1# bearing one ~uorine and twosulfur functions\ and analogues with one chlorine or one bromine substituent\ have been preparedfrom tetra~uoro!0\2!dithietane as shown in Scheme 0 ð74CB3886\ 89CB0524Ł[ X!ray data has beenobtained for "1# ð74CB4996Ł and a series of related salts has been studied spectroscopically ð76CB318Ł[

S

S

F

FF

F S

SF

F S

S

F

XF

F

AsF5

75%

X–

X = Cl, Br

AsF5F

S

SF

F

(2)

X

Scheme 1

+ +

AsF6–AsF6

–

616Carbocations

5[12[0[3 Cations Bearing Halogen\ Other Elements and "Possibly# Chalcogen Functions

5[12[0[3[0 Cations bearing two halogens and one nitrogen function

Dichloroiminium salts\ and in particular N\N!dimethyldichloroiminium chloride "2#\ are impor!tant reagents with a wide range of synthetic applications[ Dihaloiminium salts with bromine oriodine substituents are known but have been little studied[ Stable di~uoroiminium salts have notbeen described[ The chemistry of dihaloiminium salts has been reviewed by Janousek and Viehe ðB!65MI 512!90Ł and by Marhold ð72HOU"E3#544Ł[

The salt Cl1C1NH1¦SbCl5− has been prepared from cyanogen chloride\ HCl and antimony

pentachloride^ compounds BrClC1NH1¦SbCl5− and ClIC1NH1

¦SbCl5− are prepared anal!ogously from cyanogen bromide and cyanogen iodide ð53CB0175Ł[ Salts of this type can also beprepared by protonation or alkylation of carbonimidic dichlorides "isocyanide dichlorides#ð61CB2949\ 72HOU"E3#544\ 81ZAAC"506#025Ł^ an example is the protonation of Cl1C1NCl in a superacidmedium "HF and SbF5# ð81ZAAC"506#025Ł[ The method of choice for preparing N\N!dialkyl!dichloroiminium salts is\ however\ usually based on the chlorination of thiocarbonyl chloridesor thiocarbamates ð62ZOR28\ 72HOU"E3#544Ł[ The preparation can be carried out in one pot startingfrom a secondary amine\ carbon disul_de and a chlorinating agent such as chlorine or phosphoruspentachloride^ thus\ the salt "3# was prepared "80)# from pyrrolidine ð78SC1714Ł[ The dibromocompound "4# was obtained in a similar way\ by reaction of the disul_de "5# with bromine "Equation"0## ð63ZOR338Ł[ The corresponding diiodo compound "6# was prepared from the salt "2# in goodyield by heating with three equivalents of iodomethane ð68ZOR104Ł[

NMe2 Cl–

Cl

Cl+

(3)

N

Cl

Cl+

(4)

Cl– NMe2 I–

I

I+

(7)

NMe2 Br–

Br

Br+

(5)

S

S NMe2SMe2N

S(6)

Br2(1)

5[12[0[3[1 Cations bearing two halogens and one other heteroatom function

Several transition metal complexes exist in which a dihalocarbene acts as a ligand ð77CRV0182Ł[In some of these the metal complex bears an overall positive charge and the species can formally beregarded as a stabilized carbocation bearing three heteroatoms[ Structural studies have shown thatthere is considerable back donation of electrons from the metal to the dihalocarbene ligand in thesecomplexes\ so the metal to carbon bond is best regarded as a double bond[

Cationic complexes containing the CF1 ligand can be formed from tri~uoromethyl complexes byabstraction of ~uoride using antimony penta~uoride or boron tri~uoride[ The complexðCpMo"CF1#"CO#2Ł¦SbF5

− was detected in solution at low temperature from the reaction ofantimony penta~uoride with CpMoCF2"CO#2 ð67JOM"042#56Ł[ The iron complex ðCpFe"CF1#"CO#PPh2Ł¦BF3

−\ prepared in a similar manner\ was fully characterised ð74OM0729Ł[ The cor!responding dichlorocarbene complex ðCpFe"CCl1#"CO#PPh2Ł¦BF3

− was prepared by halideexchange\ with BCl2 as the Lewis acid ð74OM0729Ł[ Ruthenium"II# and osmium"II# complexes of thetype ðM"CClX#"MeCN#"CO#"PPh2#1Ł¦Y− "X�Cl or F# are formed by abstraction of a chlorideligand from neutral carbene complexes by silver"I# salts in acetonitrile ð73JOM"158#C44\ 77CRV0182Ł[

5[12[0[3[2 Cations bearing one halogen\ one chalcogen and one nitrogen function

The reaction of N\N!dimethyldichloroiminium chloride "2# with phenol or with thiophenol resultsin the formation of cations of this type "Scheme 1# ðB!65MI 512!90Ł[ Cations "7# with sulfur substituents


can also be prepared by chlorination of dithiocarbamate esters ðB!68MI 512!91Ł[ Thiocyanates RSCN"R�Me\ Ph# react with HBr to form isolable salts ðRSC"Br#NH1Ł¦Br− ð53CB2051Ł and the reactionof aryl cyanates with phosphorus pentachloride leads to the formation of the salts "8# in high yieldð61JGU86Ł[

NMe2

RS

SPCl5

X = SNMe2 Cl–

RX

Cl+

(8)

PhXH

X = O, S; R = PhNMe2 Cl–

Cl

Cl+

(3)

Scheme 2

N PCl

ArO

Cl+

(9)

3PCl6–

5[12[0[3[3 Cations bearing one halogen and two nitrogen functions

Salts of this type are well represented in the literature^ many are stable\ isolable solids[ Those inwhich the two nitrogen functions are dialkylamino groups are the best known and the methods ofpreparation of chloroformamidinium salts has been reviewed ðB!68MI 512!90Ł[ The simplest salts ofthis class are derived from cyanamides by reaction with HCl or HBr[ Cyanamide reacts with HClto give the salt H1NC"Cl#1NH1

¦Cl− as a solid which is stable for a month at room temperature inanhydrous conditions ð89JMC323Ł[ Dialkylcyanamides react with HBr in a similar wayð77JCS"P0#788Ł[ Carbodiimides react with 1 mol HCl to give salts ð"RNH#1CClŁ¦Cl− ðB!68MI 512!90Łand it is possible to form a crystalline ~uorine substituted salt "09# by reaction of"CF2#1NC"F#1NCF2 with HF:AsF4 below −29>C ð76JFC"26#148Ł[ Dimethylcyanamide has alsobeen used as the starting material for more complex salts^ examples include the sulfur!containingspecies "00# formed by reaction with sulfur dichloride ð74IC1342Ł and the conjugated iminium salts"01# which were produced from N!arylbenzamides\ phosphorus oxychloride and perchloric acidð76CC88Ł[

NHCF3 AsF6–•HF

(CF3)2N

F+

(10)

N S

Me2N

Cl+

(11)

3Cl3–

NH

Me2N

Cl+

(12)

Ph

NArClO4

–

The most general method for the preparation of chloroformamidinium salts is the chlorinationof ureas or thioureas using phosgene or similar reagents ðB!68MI 512!90Ł[ An example of the reaction\the chlorination of tetramethylurea\ is shown in Equation "1# ð68S228Ł[ Another potentially generalmethod is the reaction of dichloroiminium salts such as "2# with nitrogen nucleophiles but this isnot always successful since the reactions often proceed further\ particularly when basic amines areused as nucleophiles ðB!65MI 512!90Ł[ An example of a salt which has been prepared by this methodis "02#\ which was prepared from "2# and azidotrimethylsilane ð64C198Ł[

NMe2

Me2N

OCOCl2

89%NMe2

+ Cl–

Me2N

Cl(2)

NMe2+ Cl–

N3

Cl

(13)

618Carbocations

5[12[0[4 Cations Bearing Three Chalcogen Functions

5[12[0[4[0 Three oxygen functions

Tris"alkoxy#methylium salts\ "RO#2C¦BF3−\ are isolable species[ A review of the early work on

their preparation and properties is available ðB!60MI 512!90Ł and they are referred to in more recentreviews on carbenium ions ð76CSR64\ 82AG"E#656Ł[ The best method for their preparation is thereaction of the ortho!carbonate C"OR#3 with boron tri~uoride etherate and HBF3^ papers whichprovide good experimental details are available for the preparation of the triethoxy! ð76JOM"217#138Łand the trimethoxy! ð78SC1296Ł substituted carbenium tetra~uoroborates[ Hexachloroantimonatesalts can be made in an analogous manner[ The salt "EtO#2C¦BF3

− has also been prepared by O!alkylation of diethyl carbonate ð70LA69Ł[ The parent cation ¦C"OH#2 has been generated in asuperacid medium from di!t!butyl carbonate ð82AG"E#656Ł[

5[12[0[4[1 Three sulfur functions

There are several examples of the preparation of stable salts of carbenium ions bearing threesulfur functions[ The methods for their preparation are analogous to those used for the tris!"alkoxy#carbenium ions but\ since it is much easier to alkylate sulfur than oxygen\ a wider rangeof alkylating agents can be used[

The most convenient method of preparation is usually S!alkylation of trithiocarbonate diesters"Equation "2## ð56TL1636\ 77S11Ł[ This method has been reviewed brie~y ð55AHC"6#28Ł and there aremany more recent examples\ including the preparation of some species in which the substituentsprovide little stabilization to the cation[ Some examples "salts "03# ð67JOC567Ł\ "04# ð81JOC0585Ł and"05# ð89CB0524Ł# are shown[ Less commonly\ tetrathio!ortho!carbonates are used as startingmaterials ð56TL1636\ 83CB486Ł^ the stable salt "06# was prepared by this method ð83CB486Ł[ Tri!thiocarbonates have also been S!arylated using arenediazonium tetra~uoroborates ð71JPR558Ł[

SMe –OSO2FS

S

NC

NC

+ SMe BF4–

S

S

MeSe

MeSe

+ SMe AsF6–

S

S

F

F(F3CS)3C+ AsF6

–

(17)(14) (15) (16)

+

SR2 X–

R1S

R1SR2X

S

R1S

R1S+ (3)

5[12[0[4[2 Three selenium functions

The salt "07# was generated by Se!alkylation of the corresponding triselenocarbonate ð64TL0148Ł[Salts containing mixed sulfur and selenium substituents were also generated[

SeMe I–Se

Se

+

(18)

5[12[0[5 Cations Bearing Chalcogen and Nitrogen Functions

5[12[0[5[0 Two oxygen and one nitrogen function

In principle\ salts of this type are readily available from dichloroiminium salts and alcohols[ Thisreaction is successful with the salt "2# and phenol\ catechol and pinacol ðB!65MI 512!90Ł^ thus\ "08#was prepared from "2# and pinacol[ With simple alcohols the chloride salts are unstable\ chlorideacting as a nucleophile to displace one of the oxygen functions[ The problem is overcome with


nonnucleophilic counterions^ for example\ the salt "EtO#1C1NH1¦SbCl5− can be isolated

ð55ZAAC"233#002Ł[

NMe2 Cl–O

O

+

(19)

Another method of preparation is O!alkylation of urethanes[ N\N!Dimethylurethane wasethylated with triethyloxonium tetra~uoroborate to give "19# ð50LA"530#0Ł and the same methodwas used to prepare the salt "10# from "MeO#1C1NCO1Et ð81CB1376Ł[

NMe2 BF4–

EtO

EtO

N

MeO

MeO

OEt

OEt+ +

BF4–

(20) (21)

5[12[0[5[1 Two sulfur and one nitrogen function

These salts are most often prepared by S!alkylation of dithiocarbamates ð63BCJ287\ 74S780Ł^ forexample\ the salt "11# was prepared "74)# by methylation of the cyclic dithiocarbamate withdimethyl sulfate and subsequent reaction with sodium perchlorate "Equation "3## ð63BCJ287Ł[ Doublealkylation of dithiocarbamate salts is also possible] thus\ the salt "12# was derived fromMe1NCS1

−Na¦ and 0\1!bis"bromomethyl#benzene ð63BCJ287Ł[ An alternative method of prep!aration is N!alkylation of iminodithiocarbonates "R0S#1C1NR1 ð57T5374Ł[

SN

SSMe ClO4

–N

S

i, Me2SO4ii, NaClO4

85%+

Me Me

(22)

(4)

S

S

NMe2+ ClO4

–

(23)

5[12[0[5[2 Two selenium and one nitrogen function

Two examples of salts in which the cations bear these functional groups are "13# and "14#[ Bothwere prepared from salts containing the anion Me1NCSe1

−\ by alkylation with 0\2!dibromopropaneand 2!bromobutan!1!one\ respectively ð61BCJ378\ 79CC755Ł[

NMe2 Me2SnBr42–

Se

Se

+

2

NMe2+ –OCOCF3

Se

Se

(24) (25)

5[12[0[5[3 Two different chalcogen and one nitrogen function

Iminothiocarbonate salts unsubstituted on nitrogen can be prepared either by S!alkylation ofthiourethanes or by the addition of alcohols and HCl to thiocyanates "Scheme 2# ð72HOU"E3#566Ł[

620Carbocations

The dithiocarbamidic ester "15# can be cyclised by S!methylation and the salt "16# can be isolatedin good yield after the addition of sodium perchlorate ð68S071Ł[

NH2

R1O

S

R2I

X = INH2 X–

R2S

R1O+ R1OH, HCl

X = ClR2S N

Scheme 3

NMe2+ ClO4

–O

S

Ph

(27)

SPh

NMe2

S

O(26)

Several salts of cations bearing sulfur\ selenium and nitrogen functions have been isolated[ Anexample is the salt "17#^ this was obtained "in a 42) yield# by ring contraction of the six!memberedheterocycle "18# which was brought about by reaction with HI ð73S556Ł[

NH2+ I–

S

Se

Ph

(28)Se

N

SPh SEt

(29)

5[12[0[5[4 One oxygen and two nitrogen functions

Tetraalkylureas are alkylated on oxygen by trialkyloxonium tetra~uoroborates^ for example\ thesalt ð"Me1N#1COEtŁ¦BF3

− was prepared in high yield from tetramethylurea and triethyloxoniumtetra~uoroborate ð50LA"530#0Ł^ trimethyloxonium tetra~uoroborate has also been used ð60LA"632#0Ł[With some tetraalkyureas\ N!alkylation can compete[ An alternative procedure for the preparationof salts is the displacement of chloride from chloroformamidinium cations by alcohols or alkoxides[The salt "29# was prepared in this way "in a 46) yield# from ð"Me1N#1CClŁ¦Cl− ð60LA"632#0Ł[ Aninteresting example of this reaction is the preparation of the salt "20# "Equation "4## ð56CB2208Ł[Salts unsubstituted on nitrogen are obtained by the addition of alcohols to cyanamide^ thus\ðBnOC"NH1#1Ł¦ −OTs was prepared "in an 70) yield# from benzyl alcohol\ cyanamide and p!toluenesulfonic acid in dry chloroform ð76TL0858Ł[

NMe2 Cl–

Me2N

PhO+

(30)

MeOH

74%NH2 SbCl6–

N3

MeO+NH2 SbCl6–

N3

Cl+

(31)

(5)

5[12[0[5[5 One sulfur and two nitrogen functions

Thioureas are readily alkylated on sulfur by a wide range of electrophiles to give stable iso!thiouronium salts "21# "Equation "5## ð72HOU"E3#589Ł[ This is by far the most important method ofpreparation of these salts[ Thioureas can also be S!arylated by means of arenediazonium salts[ By


analogy with the preparation of the salt "29#\ S!arylisothiouronium salts can also be prepared bythe reaction of chloroformamidinium salts with thiophenols ð58LA"616#117Ł[

NR12

R12N

SR2X

NR12X–

R12N

R2S+

(32)

(6)

5[12[0[5[6 One selenium and two nitrogen functions

The reaction of selenoureas with alkylating agents is analogous to that of thioureas and stablesalts "22# can be isolated ð51JOC1788\ 75NJC40Ł[

NR12X–

R12N

R2Se+

(33)

5[12[0[6 Cations Bearing Chalcogen\ Metal and "Possibly# Nitrogen Functions

There are two general methods for the preparation of cationic carbene complexes of this class] "i#alkylation of a ligand on sulfur or oxygen and "ii# nucleophilic addition to an isocyanide ligand[ Anexample of a preparation of the _rst type is the formation of the mercury complex shown inEquation "6# ð56AG"E#459Ł[ The platinum complex "23# was similarly prepared by S!methylation ofa thioamide function ð64IC0402Ł[ The complex "24# was formed by alkylation of both sulfur atomsof a CS1 ligand by 0\1!dibromoethane ð65JOM"096#C26Ł[ Several related preparations have beenreported ð63JCS"D#240\ 64JCS"D#828\ 64JOM"89#C23Ł[ The second approach is illustrated by the prep!aration of the platinum complex "25# by addition of ethanethiol to isocyanide ligands of "26#ð61IC1958Ł[ Attempts to add alcohols to coordinated isocyanides are generally unsuccessful\ althoughan intramolecular addition has been reported ð63AG"E#488Ł[

(7)Me3O+ BF4

–

O

Et2N Hg NEt2

O MeO

Et2N Hg NEt2

MeO

2+

2BF4–

+

2PF6–Pt

SMe

NMe2

Cl

PPh3

PPh3

Os(Br)(CO)(PPh3)2 ClO4–

S

SFSO3

– Pt

MeHN SEt

MeHN SEt

NMeMeN

+

(34) (35) (36)

2+

[Pt(CNMe)4]2+ 2PF6–

(37)

5[12[0[7 Cations Bearing Three Nitrogen Functions

Methods for the preparation of guanidines have been described in Chapter 5[10[ Guanidines arestrong bases and excellent nucleophiles\ so that a great many guanidinium salts have been preparedby protonation or alkylation of guanidines[ Even guanidines bearing electron!withdrawing sub!stituents can be alkylated] an example is the preparation of the guanidinium salt "27# "in a 57)

622Carbocations

yield# by alkylation of N!cyano!N?\N?\N?\N?!tetramethylguanidine with triethyloxonium tetra!~uoroborate ð73CB491Ł[

NCNEt BF4–

Me2N

Me2N

+

(38)

Salts "28# and "39# with cations bearing one and two azido functions have been prepared bydisplacement of chloride from the corresponding chloro!substituted cations ð56CB2164Ł[ Tris"azido#carbenium hexachloroantimonate "30# is isolated in high yield from the reaction of tetra!chloroantimony"V# azide\ "SbCl3N2#1\ with carbon tetrachloride ð55AG"E#730\ 56CB2614Ł[ This saltreacts with PCl2 ð68AG"E#582Ł and with PBr2 ð79ZAAC"357#054Ł to give the new salts "31^ X�Cl orBr#[

NH2 Cl–N3

H2N

+

(39)

NH2 SbCl6–

N3

N3

+

(40)

N

N

N

+

(42)

X3P

X3P PX3

SbX6–

N3 SbCl6–

N3

N3

+

(41)

5[12[0[8 Cations Bearing Nitrogen and Other Element Functions

A few salts have been described in which the cation bears two nitrogen and one phosphorusfunction ð61JOC1629\ 67JPR278Ł[ The most stable of these is the crystalline salt "32# which was preparedas shown in Equation "7# ð67JPR278Ł[ The salt "33#\ described by the authors as a {cationic halfylide|\ has also been prepared ð67CB1340Ł[ There are a number of cationic carbene complexes of thisclass known\ of which "34# is an example ð82OM2394Ł^ this was prepared from the stable carbeneand silver tri~ate[

Cl Cl–Me2N

Me2N

+

P(O)Ph2 Cl–Me2N

Me2N

+

(43)

Ph2POPri

81%

(8)

NEt2 BF4–

Me3P

Me3P

(44)

AgNAr

ArN

ArN

NAr

+

Tf–

(45)

+

5[12[0[09 Cations Bearing Phosphorus and Silicon Functions

The salt "35# has been prepared as shown in Equation "8#^ it is a colourless solid which is unstableabove −29>C ð80AG"E#698\ 82PS"65#10Ł[ Crystal structure determinations carried out on closely relatedsalts show that both phosphorus and carbon are trigonal planar] the salt can be regarded as thephosphorus analogue of an iminium salt\ with stabilization of the carbenium ion by the lone pair


on phosphorus[ The salt "36# has also been isolated but in this case the nitrogen substituents onphosphorus bear much of the positive charge ð78JA5742Ł[

P(Cl)But2

TMS

TMS

PBut2 AlCl4–

TMS

TMS

+

(46)

AlCl3 (9)

P(NPri2)2 Tf–

TMS

TMS

(47)

+

5[12[1 CARBON!CENTERED RADICALS BEARING THREE HETEROATOMFUNCTIONS

No carbon!centered radicals bearing three heteroatom functions can be regarded as {stable| inthat they cannot be isolated and handled\ but a few such radicals have signi_cant lifetimes "rangingfrom a few seconds to a few hours# in solution[ Such radicals have been described as {persistent|ð65ACR02Ł[ These radicals bear silicon\ phosphorus or sulfur substituents and their increased lifetimecan be ascribed to steric factors rather than to electron delocalization[

The tris"trimethylsilyl#methyl radical =C"TMS#2 can be generated by decomposition ofð"TMS#2CŁ1Hg ð69CC448Ł or by reduction of "TMS#2CI ð80CC0597Ł[ This radical is long!lived insolution[ A number of carbon radicals bearing three sulfur functions can also be described aspersistent\ among them =C"SCF2#2\ which is generated reversibly from its dimer at room temperatureð68JA5171Ł\ and =C"SCF2#1SC5F4\ which is produced from its dimer at 039Ð089>C ð73T3852Ł[ Anumber of other radicals bearing three sulfur functions or two sulfur and one silicon function canbe produced by thermal dissociation of their dimers ð66CB1779Ł[ A series of persistent radicals "37#has been produced by the reaction of the dithioesters "38^ X�O or S# with a wide range of radicalsR=\ including MeS=\ Me= and Ph2Pb= ð82JA7333Ł[

P(OEt)2

MeS

S

P(OEt)2

MeS

RS

(48) (49)

•X X


References to Volume 6

EXPLANATION OF THE REFERENCE SYSTEM

Throughout this work, references are designated by a number-lettering coding of which the firsttwo numbers denote tens and units of the year of publication, the next one to three letters denotethe journal, and the final numbers denote the page. This code appears in the text each time areference is quoted; the advantages of this system are outlined in the Introduction. The system hasbeen used previously in "Comprehensive Heterocyclic Chemistry," eds A. R. Katritzky and C. W.Rees, Pergamon, Oxford, 1984 and is based on that used in the following two monographs: (a) A. R.Katritzky and J. M. Lagowski, "Chemistry of the Heterocyclic N-Oxides," Academic Press,New York, 1971; (b) J. Elguero, C. Marzin, A. R. Katritzky and P. Linda, "The Tautomerism ofHeterocycles," in "Advances in Heterocyclic Chemistry," Supplement 1, Academic Press, NewYork, 1976.

The following additional notes apply:

1. A list of journal codes in alphabetical order, together with the journals to which they refer, isgiven immediately following these notes. Journal names are abbreviated throughout using theCASSI (Chemical Abstracts Service Source Index) system.

2. Each volume contains all the references cited in that volume; no separate lists are given forindividual chapters.

3. The list of references is arranged in order of (a) year, (b) journal in alphabetical order ofjournal code, (c) part letter or number if relevant, (d) volume number if relevant, (e) page number.

4. In the reference list the code is followed by (a) the complete literature citation in the con-ventional manner and (b) the number(s) of the page(s) on which the reference appears, whether inthe text or in tables, schemes, etc.

5. For nontwentieth-century references the year is given in full in the code.6. For journals which are published in separate parts, the part letter or number is given (when

necessary) in parentheses immediately after the journal code letters.7. Journal volume numbers are not included in the code numbers unless more than one volume

was published in the year in question, in which case the volume number is included in parenthesesimmediately after the journal code letters.

8. Patents are assigned appropriate three-letter codes.9. Frequently cited books are assigned codes.10. Less common journals and books are given the code "MI" for miscellaneous with the whole

code for books prefixed by the letter "B-".11. Where journals have changed names, the same code is used throughout, e.g. CB refers to

both Chem. Ber. and to Bar. Dtsch. Chem. Ges.

Journal CodesAAC Antimicrob. Agents Chemother.ABC Agric. Biol. Chem.AC Appl. Catal.AC(P) Ann. Chim. (Paris)AC(R) Ann. Chim. (Rome)ACH Acta Chim. Acad. Sci. Hung.

735

736 References

ACR Ace. Chem. Res.ACS Acta Chem. Scand.ACS(A) Acta Chem. Scand., Ser. AACS(B) Acta Chem. Scand., Ser. BAF Arzneim.-Forsch.AFC Adv. Fluorine Chem.AG Angew. Chem.AG(E) Angew. Chem., Int. Ed. Engl.AHC Adv. Heterocycl. Chem.AHCS Adv. Heterocycl. Chem. SupplementAI Anal. Instrum.AJC Aust. J. Chem.AK Ark. KemiAKZ Arm. Khim. Zh.AM Adv. Mater. (Weinheim, Ger.)AMLS Adv. Mol. Spectrosc.AMS Adv. Mass. Spectrom.ANC Anal. Chem.ANL Acad. Naz. LnceiANY Ann. N. Y. Acad. Sci.AOC Adv. Organomet. Chem.AP Arch. Pharm. (Weinheim, Ger.)APO Adv. Phys. Org. Chem.AQ An. Quim.AR Annu. Rep. Prog. Chem.AR(A) Annu. Rep. Prog. Chem., Sect. AAR(B) Annu. Rep. Prog. Chem., Sect. BARP Annu. Rev. Phys. Chem.ASI Acta Chim. Sin. Engl. Ed.ASIN Acta Chim. Sin.AX Acta Crystallogr.AX(A) Acta Crystallogr., Part AAX(B) Acta Crystallogr., Part BB BiochemistryBAP Bull. Acad. Pol. Sci., Ser. Sci. Chim.BAU Bull. Acad. Sci. USSR, Div. Chim. Sci.BBA Biochim. Biophys. ActaBBR Biochim. Biophys. Res. Commun.BCJ Bull. Chem. Soc. Jpn.BEP Belg. Pat.BJ Biochem. J.BJP Br. J. Pharmacol.BMC Bioorg. Med. Chem. Lett.BP Biochem. Biopharmacol.BPJ Br. Polym. J.BRP Br. Pat.BSB Bull. Soc. Chim. Belg.BSF Bull. Soc. Chim. Fr.BSF(2) Bull. Soc. Chim. Fr., Part 2C ChimiaCA Chem. Abstr.CAN CancerCAR Carbohydr. Res.CAT Chim. Acta Turc.CB Chem. Ber.

References 131

CBR Chem. Br.CC J. Chem. Soc, Chem. Commun.CCA Croat. Chem. ActaCCC Collect. Czech. Chem. Commun.CCR Coord. Chem. Rev.CE Chem. ExpressCEN Chem. Eng. NewsCHE Chem. Heterocycl. Compd. (Engl. Transl.)CHEC Comp. Heterocycl. Chem.CI(L) Chem. Ind. (London)CI(M) Chem. Ind. (Milan)CJC Can. J. Chem.CJS Can. J. Spectrosc.CL Chem. Lett.CLY Chem. ListyCM Chem. Mater.CMC Comp. Med. Chem.COC Comp. Org. Chem.COMC-I Comp. Organomet. Chem., 1st edn.COS Comp. Org. Synth.CP Can. Pat.CPB Chem. Pharm. Bull.CPH Chem. Phys.CPL Chem. Phys. Lett.CR C. R. Hebd. Seances Acad. Sci.CR(A) C. R. Hebd. Seances Acad. Sci., Ser. ACR(B) C. R. Hebd. Seances Acad. Sci., Ser. BCR(C) C. R. Hebd. Seances Acad. Sci., Ser. CCRAC Crit. Rev. Anal. Chem.CRV Chem. Rev.CS Chem. Ser.CSC Cryst. Struct. Commun.CSR Chem. Soc. Rev.CT Chem. Tech.CZ Chem.-Ztg.CZP Czech. Pat.DIS Diss. Abstr.DIS(B) Diss. Abstr. Int. B.DOK Dokl. Akad. Nauk SSSRDP Dyes Pigm.E ExperientiaEC Educ. Chem.EF Energy FuelsEGP Ger. (East) Pat.EJM Eur. J. Med. Chem.EUP Eur. Pat.FCF Forschr. Chem. Forsch.FCR Fluorine Chem. Rev.FES Farmaco Ed. Sci.FOR Forschr. Chem. Org. Naturst.FRP Fr. Pat.G Gazz. Chim. Ital.GAK Gummi Asbest Kunstst.GEP Ger. Pat.GEP(O) Ger. Pat. Offen.

738 References

GSM Gen. Synth. MethodsH HeterocyclesHAC Heteroatom Chem.HC Chem. Heterocycl. Compd.HCA Helv. Chim. ActaHOU Methoden Org. Chem. (Houben-Weyl)HP Hydrocarbon ProcessIC Inorg. Chem.ICA Inorg. Chim. ActaIEC Ind. Eng. Chem. Res.IJ Isr. J. Chem.IJC Indian J. Chem.IJC(A) Indian J. Chem., Sect. AIJC(B) Indian J. Chem., Sect. BIJM Int. J. Mass Spectrom. Ion Phys.IJQ Int. J. Quantum Chem.US Int. J. Sulfur Chem.IJS(A) Int. J. Sulfur Chem., Part AIJS(B) Int. J. Sulfur Chem., Part BIS Inorg. SynthIZV Izv. Akad. Nauk SSSR Ser. Khim.JA J. Am. Chem. Soc.JAN J. Antibiot.JAP Jpn. Pat.JAP(K) Jpn. KokaiJBC J. Biol. Chem.JC J. Chromatogr.JCC J. Coord. Chem.JCE J. Chem. Ed.JCED J. Chem. Eng. DataJCI J. Chem. Inf. Comput. Sci.JCP J. Chem. Phys.JCPB J. Chim. Phys. Physico-Chim. Biol.JCR(M) J. Chem. Res. (M)JCR(S) J. Chem. Res. (S)JCS J. Chem. Soc.JCS(A) J. Chem. Soc. (A)JCS(B) J. Chem. Soc. (B)JCS(C) J. Chem. Soc. (C)JCS(D) J. Chem. Soc, Dalton Trans.JCS(Fl) J. Chem. Soc, Faraday Trans. 1JCS(F2) J. Chem. Soc, Faraday Trans. 2JCS(Pl) J. Chem. Soc, Perkin Trans. 1JCS(P2) J. Chem. Soc, Perkin Trans. 2JCS(S2) J. Chem. Soc. (Suppl. 2)JEC J. Electroanal. Chem. Interfacial Electrochem.JEM J. Energy Mater.JES J. Electron. Spectrosc.JFA J. Sci. Food. Agri.JFC J. Fluorine Chem.JGU J. Gen. Chem. USSR (Engl. Transl.)JHC J. Heterocycl. Chem.JIC J. Indian Chem. Soc.JINC J. Inorg. Nucl. Chem.JLC J. Liq. Chromatogr.

References 739

JMAS J. Mat. Sci.JMC J. Med. Chem.JMOC J. Mol. Catal.JMR J. Magn. Reson.JMS J. Mol. Sci.JOC J. Org. Chem.JOM J. Organomet. Chem.JOU J. Org. Chem. USSR (Engl. Transl.)JPC J. Phys. Chem.JPJ J. Pharm. Soc. Jpn.JPO J. Phys. Org. Chem.JPP J. Pharm. Pharmacol.JPR J. Prakt. Chem.JPS J. Pharm. Sci.JPS(A) J. Polym. Sci., Polym. Chem., Part AJPU J. Phys. Chem. USSR (Engl. Transl.)JSC J. Serbochem. Soc.JSP J. Mol. Spectrosc.JST J. Mol. Struct.K KristallografiyaKFZ Khim. Farm. Zh.KGS Khim. Geterotsikl. Soedin.KO Kirk-Othmer Encyc.KPS Khim. Prir. Soedin.L LangmuirLA Liebigs Ann. Chem.LC Liq. Cryst.LS Life Sci.M Monatsh. Chem.MAC Macromol. Chem.MC Mendeleev Chem. J. (Engl. Transl.)MCLC Mol. Cryst. Liq. Cryst.MI Miscellaneous [book/journal]MIP Miscellaneous Pat.MM MacromoleculesMP Mol. Phys.MRC Magn. Reson. Chem.N NaturwissenschaftenNAT Nat.NEP Neth. Pat.NJC Nouv. J. Chim.NKK Nippon Kagaku Kaishi (J. Chem. Soc. Jpn.)NKZ Nippon Kagaku ZasshiNZJ N. Z. J. Sci. Technol.OCS Organomet. Synth.OM OrganometallicsOMR Org. Magn. Reson.OMS Org. Mass Spectrom.OPP Org. Prep. Proced. Int.OR Org. React.OS Org. Synth.OSC Org. Synth., Coll. Vol.P PhytochemistryPA Polym. AgePAC Pure Appl. Chem.

740 References

PAS Pol. Acad. Sci.PB Polym. Bull.PC Personal CommunicationPCS Proc. Chem. Soc.PHA PharmaziPHC Prog. Heterocycl. Chem.PIA Proc. Indian Acad. Sci.PIA(A) Proc. Indian Acad. Sci., Sect. APJC Pol. J. Chem.PJS Pak. J. Sci. Ind. Res.PMH Phys. Methods Heterocycl. Chem.PNA Proc. Natl. Acad. Sci. USAPOL PolyhedronPP Polym. Prepr.PRS Proceed. Roy. Soc.PS Phosphorus SulfurQR Q. Rev., Chem. Soc.QRS Quart. Rep. Sulfur. Chem.QSAR Quant. Struct. Act. Relat. Pharmacol. Chem. Biol.RC Rubber Chem. Technol.RCM Rapid Commun. Mass Spectrom.RCP Rec. Chem. Prog.RCR Russ. Chem. Rev. (Engl. Transl.)RHA Rev. Heteroatom Chem.RJ Rubber J.RP Rev. Polarogr.RRC Rev. Roum. Chim.RS Ric. Sci.RTC Reel. Trav. Chim. Pays-BasRZC Rocz. Chem.S SynthesisSA Spectrochim. ActaSA(A) Spectrochim. Acta, Part ASAP S. Afr. Pat.SC Synth. Commun.SCI ScienceSL SynlettSM Synth. Met.SR Sulfur ReportsSRI Synth. React. Inorg. Metal-Org. Chem.SS Sch. Sci. Rev.SST Org. Compd. Sulphur, Selenium, Tellurium [R. Soc. Chem. series]SUL Sulfur LettersSZP Swiss Pat.T TetrahedronT(S) Tetrahedron, Suppl.TA Tetrahedron AsymmetryTAL TalantaTCA Theor. Chim. ActaTCC Top. Curr. Chem.TCM Tetrahedron, Comp. MethodTFS Trans. Faraday Soc.TH ThesisTL Tetrahedron Lett.TS Top. Stereochem.

References 741

UK Usp. Khim.UKZ Ukr. Khim. Zh. (Russ. Ed.)UP Unpublished ResultsURP USSR Pat.USP US Pat.WCH Wiadom. Chem.YGK Yuki Gosei Kagaku KyokaishiYZ Yakugaku Zasshi (J. Pharm. Soc. Jpn.)ZAAC Z. Anorg. Allg. Chem.ZAK Zh. Anal. Khim.ZC Z. Chem.ZN Z. Naturforsch.ZN(A) Z. Naturforsch., Teil AZN(B) Z. Naturforsch., Teil BZOB Zh. Obshch. Khim.

, ZOR Zh. Org. Khim.ZPC Hoppe-Seyler's Z. Physiol. Chem.ZPK Zh. Prikl. Khim.

VOLUME 6 REFERENCES

1854LA(92)346 A. W. Williamson and G. Kay; Justus Liebigs Ann. Chem., 1854, 92, 346. 68

1854PRS135 A. W. Williamson and G. Kay; Proceed. Roy. Soc, 1854,7, 135. 68

1866BSF435 M. H. Gal; Bull. Soc. Chim. Fr., 1866,6,435. 452

1869BSF198 M. D. Schiitzenberger; Bull. Soc. Chim. Fr., 1869, 12, 198. 4121869ZC624 O. Loew; Z. Chem., 1869,624. 2211870CB730 R. Gerstl; Ber. Dtsch. Chem. Ges., 1870,3,730. 412

1870LA(156)60 T. Bolas and C. E. Groves; Justus Liebigs Ann. Chem., 1870, 156, 60. 215

1872JPR(2)477 F. Salomon; J. Prakt. Chem. (2), 1872, 5, 477. 471

1877CB185 S. Gabriel; Ber. Dtsch. Chem. Ges., 1877,10, 185. 811877CB678 J. H. van't Hoff; Ber. Dtsch. Chem. Ges., 1877,10, 678. 216, 2211877LA(189)159 H. Schiff; Justus Liebigs Ann. Chem., 1877, 189, 159. 5081878BSF(2)185 M. Tschemiak; Bull. Soc. Chim. Fr., Part 2, 1878,30, 185. 6101878CB2265 M. Dennstedt; Ber. Dtsch. Chem. Ges., 1878, 11,2265. 811878G233 E. Paterno; Gazz. Chim. Ital., 1878,8,233. 411,412

1879CB115 A. Deutsch; Ber. Dtsch. Chem. Ges., 1879,12, 115. 68

1882CB2685 F. Tiemann; Ber. Dtsch. Chem. Ges., 1882, 13,2685. 69

1883CB352 A. Pinner; Ber. Dtsch. Chem. Ges., 1883, 16,352. 70

1883CB1643 A. Pinner; Ber. Dtsch. Chem. Ges., 1883, 16, 1643. 70

1884CB297 B. Rathke; Ber. Dtsch. Chem. Ges., 1884, 17,297. 641

1887JPR99 W. Hentschel; J. Prakt. Chem., 1887,36,99. 4151887LA(240)192 M. Arnhold; Justus Liebigs Ann. Chem., 1887, 240, 192. 2271887LA(240)225 R. Holand; Justus Liebigs Ann. Chem., 1887, 240, 225. 213, 2271890CB1414 E. Laves; Ber. Dtsch. Chem. Ges., 1890,23, 1414. 911890CB3226 E. Stauffer; Ber. Dtsch. Chem. Ges., 1890,23,3226. 254

1892CB188 A. Besson; Ber. Dtsch. Chem. Ges., 1892,25, 188. 2221892CB347 E. Laves; Ber. Dtsch. Chem. Ges., 1892, 25, 347. 90, 911892CB361 E. Laves; Ber. Dtsch. Chem. Ges., 1892,25,361. 90

1893CB1990 H. Erdmann; Ber. Dtsch. Chem. Ges., 1893,26, 1990. 412

742 References

1895BSF444 A. Besson; Bull. Soc. Chim. Fr., 1895, 13,444. 4201895JPR(2)472 T. Curtius and K. Heidenreich; J. Prakt. Chem. (2), 1895, 52, 472. 5111895MI 614-01 F. Lengfeld and J. Stieglitz; Am. Chem. J., 1895,17, 98. 452

1897JPR71 E. Beckmann;/. Prakt. Chem., 1897,56,71. 570,571

1898LA(300)145 A. Einhorn; Justus Liebigs Ann. Chem., 1898, 300, 145. 484

1899CB1116 L. Gattermann; Ber. Dtsch. Chem. Ges., 1899, 32, 1116. 448

1899GEP114396 Farbenfabrik Bayer, Ger. Pat. 114396 (1899). 484

OOCB1O58 M. Busch and P. Bauer; Ber. Dtsch. Chem. Ges., 1900,33, 1058. 653

03CB1280 L. Knorr and P. Rossler; Ber. Dtsch. Chem. Ges., 1903,36, 1280. 48503LA(329)l 16 J. Sand and F. Singer; Justus Liebigs Ann. Chem., 1903, 329, 116. 207

03MI607-01 F. Swarts; Chem. Zentr., 1903, II, 709. 216

05CB561 A. E. Tschitschibabin; Ber. Dtsch. Chem. Ges., 1905,38,561. 77

06CB857 H. Leuchs; Ber. Dtsch. Chem. Ges., 1906,39,857. 48606LA(345)334 A. von Bartal; Justus Liebigs Ann. Chem., 1906, 345, 334. 417, 42007CB1740 B. Holmberg; Ber. Dtsch. Chem. Ges., 1907,40, 1740. 83,84,9107LA(353) 131 B. Holmberg; Justus Liebigs Ann. Chem., 1907, 353, 131. 83, 8407MI614-01 A. von Bartal; Z. Anorg. Chem., 1907,56,49. 420

09JA1220 W. M. Dehn; J. Am. Chem. Soc, 1909,31, 1220. 213,223

10JCS798 L. Mond, H. Hirtz and M. D. Cowap; J. Chem. Soc, 1910, 798. 522, 524

11BSF1308 J. I. Iotsitch and F. Kochlelov; Bull. Soc Chim. Fr., 1911, 10, 1308. 7711CB3235 J. Houben and K. M. L. Schultze; Ber. Dtsch. Chem. Ges., 1911, 44, 3235. 84

11LA(384)322 F. Arndt; Justus Liebigs Ann. Chem., 1911, 384, 322. 306

12CB2942 J. Houben; Ber. Dtsch. Chem. Ges., 1912,45,2942. 84

13CB1426 H. Staudinger and E. Anthes; Ber. Dtsch. Chem. Ges., 1913, 46, 1426. 412, 417, 41813CB2447 J. Houben and E. Schmidt; Ber. Dtsch. Chem. Ges., 1913,46,2447. 625

13LA(396)1 F. Arndt; Justus Liebigs Ann. Chem., 1913,396, 1. 302

14JPR415 H. J. Prins; J. Prakt. Chem., 1914,89,415. 4

15CR(156)652 M. Lantenois; C. R. Hebd. Seances Acad. Sci., 1915,156, 652. 21618CB669 H. Rathsburg; Ber. Dtsch. Chem. Ges., 1918,51,669. 222,226B-18MI 607-01 B. Prager, P. Jacobsen, P. Schmidt and D. Stern; in "Beilsteins Handbuch der Organischen

Chemie," 4th edn., Hauptwerk, Deutsche Chemische Gesellschaft, Springer-Verlag, Berlin,1918. 118

19CR(169)17 V. Grignard and E. Urbain; C. R. Hebd. Seances Acad. Sci., 1919, 169, 17. 412, 41319JPC498 H. P. Hood and H. R. Murdock; J. Phys. Chem., 1919,23,498. 41520CB601 J. von Braun and K. Rath; Ber. Dtsch. Chem. Ges., 1920,53,601. 44420JCS708 F. D. Chattaway and E. Saerens; J. Chem. Soc, 1920,117,708. 48320JCS1410 R. H. Atkinson, C. T. Heycock and W. J. Pope; / . Chem. Soc, 1920,117, 1410. 411, 41220JPR79 W. Steinkopf and J. Herold; J. Prakt. Chem., 1920, 101,79. 409

21JCS1222 C. K. Ingold and W.J.Powell; J. Chem. Soc, 1921,119, 1222. 69

22AG489 F. Feist; Angew. Chem., 1922,35,489. 252

23CB979 H. Pauly and H. Schanz; Ber. Dtsch. Chem. Ges., 1923,56,979. 2723JCS2882 D. L. Hammick; J. Chem. Soc, 1923,2882. 28

24JA2090 J. E. Driver; J. Am. Chem. Soc, 1924,46,2090. 6924JCS442 R. A. Gotts and L. Hunter; J. Chem. Soc, 1924, 125,442. 26124JCS( 125)2259 C. F. Allpress and W. Maw; J. Chem. Soc, 1924, 125, 2259. 46724MI 614-01 E. Biesalski; Z. Angew. Chem., 1924, 37, 314 (Chem. Abslr., 1924, 18, 2480). 412

25JPR125 F. Mauthner; J. Prakt. Chem., 1925,110, 125. 27

26BSB412 F. Swarts; Bull. Soc Chim. Belg., 1926,35,412. 6826G847 M. Garino and E. Teofili; Gazz. Chim. Itai, 1926,56,847. 42026JA1736 H. E. French and A. F. Wirtel; / . Am. Chem. Soc, 1926,48, 1736. 504

References 143

26JCS2263 W. R. H. Hurtley and S. Smiles; J. Chem. Soc, 1926,2263. 8326LA(446)260 E. Bamberger, R. Padova and E. Ormerod; Justus Liebigs Ann. Chem., 1926, 446, 260. 653

27BSF1041 A. Job and A. Cassal; 5«//. Soc. Chim.Fr., 1927,41, 1041. 52227BSF1251 J.F.Dumnd; Bull. Soc. Chim.Fr., 1927,41, 1251. 21627CB1424 E. Speyer and H. Wolf; Ber. Dtsch. Chem. Ges., 1927,60, 1424. 52327CRV109 G. M. Dyson; Chem. Rev., 1927,4, 109. 411,41227JCS2658 J. E. Marsh and R. J. F. Struthers; J. Chem. Soc., 1927,2658. 207

28AP(266)277 K. W. Rosenmund and H. Doring; Arch. Pharm. (Weinheim, Ger.), 1928, 266, 277. 43128CR(187)564 A. Job and J. Rouvillois; C. R. Hebd. Seances Acad. Scl, 1928,187, 564. 52228GEP516281 G. Steimmig and M. Wittwer, Ger. Pat. 516281 (1928) {Chem. Abstr., 1931, 25, 1840). 46728G443 L. Belladen, M. Noli and A. Sommariva; Gazz. Chim. ltal, 1928, 58, 443. 41228JA516 P. P. T. San; J. Am. Chem. Soc, 1928,50,516. 70B-28MI 607-01 F. Richter; in "Beilsteins Handbuch der Organischen Chemie," 4th edn., Erstes Ergan-

zungswerk, Deutsche Chemische Gesellschaft, Springer-Verlag, Berlin, 1928. 213

29MI616-01 G. Eyber; Z. Phys. Chem., 1929, 144A, 1. 523

30CB1221 W. Manchot and G. Lehmann; Ber. Dtsch. Chem. Ges., 1930, 63, 1221. 412, 41830GEP531402 M. Naumann; Ger. Pat. 531402 (1930) (Chem. Abstr., 1931, 25, 5523). 5223OJPR81 V. V. Nekrasov and N. N. Mel'nikov; J. Prakt. Chem., 1930,126, 81. 23030JPR210 V. V. Nekrasov and N. N. Mel'nikov; J. Prakt. Chem., 1930,126, 210. 23030RTC1107 H. J. Backer; Reel. Trav. Chim. Pays-Bas, 1930,49, 1107. 91

31GEP547025 M. Naumann; Ger. Pat. 547 025 (1931) (Chem. Abstr., 1932, 26, 3632). 52231JCS2637 D. T. Gibson; J. Chem. Soc, 1931,2637. 9131LA(489)7 L. Birckenbach and K. Sennewald; Justus Liebigs Ann. Chem., 1931,489, 7. 612B-31MI 615-01 H. Meyer; "Analyse und Konstitutionsermittlung organischer Verbindungen," Springer,

Berlin, 1931, p. 367. 48431USP1961622 H. S. Nutting and P. S. Petrie (Dow Chem. Co.); US Pat., 1961622 (1931) (Chem. Abstr.,

1934, 28,4746). 212, 22531ZAAC(201)245 O. Ruff and R. Keim; Z. Anorg. Allg. Chem., 1931, 201, 245. 217, 220

32CB65 G. Endres; Ber. Dtsch. Chem. Ges., 1932,65,65. . 61232CB546 L. Birchenbach and K. Sennewald; Ber. Dtsch. Chem. Ges., 1932, 65, 546. 222, 22732CB1192 M. Bergmann and L. Zervas; Ber. Dtsch. Chem. Ges., 1932,65, 1192. 48732JA1622 C. A. Kraus and H. S. Nutting; J. Am. Chem. Soc, 1932,54, 1622. 18532JA2025 W. H. Hunter and D. E. Edgar; J. Am. Chem. Soc, 1932,54, 2025. 21532JA2964 P. P. T. Sah and T. S. Ma; J. Am. Chem. Soc, 1932, 54,2964. 68

33BSB102 F. Swarts; Bull. Soc. Chim. Belg., 1933,42, 102. 214,22533CB567 A. Schonberg and A. Stephenson; Ber. Dtsch. Chem. Ges., 1933, 66, 567. 253, 25433JA3851 H. W. Post and E. R. Erickson; / . Am. Chem. Soc, 1933, 55, 3851. 68, 7933JCS306 D. W. Cowie and D. T. Gibson; J. Chem. Soc, 1933, 306. 9033JIC537 H. C. Goswami and P. B. Sarker; J. Indian Chem. Soc, 1933,10, 537. 42233MI 603-01 P. P. T. Sah; J. Chinese Chem. Soc, 1933,1, 100 (Chem. Abstr., 1933, 27, 5729). 7033RTC437 H. J. Backer and P. L. Stedehouder; Reel. Trav. Chim. Pays Bas, 1933, 52, 437. 81, 9133RTC923 H. J. Backer and P. L. Stedehouder; Reel. Trav. Chim. Pays-Bas, 1933, 52, 923. 30633RTC1039 H. J. Backer and P. L. Stedehouder; Reel. Trav. Chim. Pays-Bas, 1933, 52, 1039. 306, 307

34BSF244 A. Wahl; Bull Soc. Chim. Fr., 1934,1,244. 50034GEP676049 K. W. Rosenmund, Ger. Pat. 676 049 (1934) (Chem. Abstr., 1939, 33, 6529). 48434JA1455 H. G. Vesper and G. K. Rollefson; J. Am. Chem. Soc, 1934, 56, 1455. 22134JA2007 M. P. Matuszak; J. Am. Chem. Soc, 1934,56,2007. 42934JCS822 J. M.Connolly and G.M.Dyson; J. Chem. Soc, 1934,822. 23234ZAAC(221)154 O. Ruff and G. Miltschitzky; Z. Anorg. Allgem. Chem., 1934, 221, 154. 409

35CB1513 A. Binz and B. Hughes; Ber. Dtsch. Chem. Ges., 1935,68, 1513. 25835CB2151 H. Scheibler and M. Depner; Ber. Dtsch. Chem. Ges., 1935,68B, 2151. 6935JA217 E. P. Kohler and M. Tishler; J. Am. Chem. Soc, 1935,57,217. 25435JA2480 L. G. S. Brooker and F. L. White; J. Am. Chem. Soc, 1935, 57, 2480. 7035RTC249 H. J. Prins; Reel. Trav. Chim. Pays-Bas, 1935,54,249. 435RTC307 H. J. Prins and F. J. W. Engelhard; Reel. Trav. Chim. Pays-Bas, 1935, 54, 307. 435ZAAC(221)321 W. Hieber and E. Romberg; Z. Anorg. Allg. Chem., 1935, 221, 321. 522

36BCJ157 H. Suginome and S. Umezawa; Bull. Chem. Soc. Jpn., 1936, 11, 157. 4936CB299 O. Ruff; Ber. Dtsch. Chem. Ges., 1936,69,299. 21236CB684 O. Ruff and M. Giese; Ber. Dtsch. Chem. Ges., 1936,69,684. 44136CB1356 H. G. Grimm and H. Metzger; Ber. Dtsch. Chem. Ges., 1936,69, 1356. 59736CB2358 J. Houben and R. Zivadinovitsch; Ber. Dtsch. Chem. Ges., 1936, 69, 2358. 62536JA529 F. Beyerstedt and S. M. McElvain; / . Am. Chem. Soc, 1936, 58, 529. 7436JCS1273 E. N. Abrahart; J. Chem. Soc, 1936, 1273. 501

744 References

36JCS1693 F. D. Chattaway, J. G. N. Drewitt and G. D. Parkes; J. Chem. Soc, 1936, 1693. 65336ZAAC(226)385 W. Manchot and W. J. Manchot; Z. Anorg. Allg. Chem., 1936, 226, 385. 524

37CB1080 W. Koblitz, H. Meissner and H. J. Schumacher; Ber. Dtsch. Chem. Ges., 1937, 70, 1080. 41837CR(204)1927 J. Lecomte, H. Volringer and A. Tchakirian; C. R. Hebd. Seances Acad. Sci., 1937, 204,

1927. 221,222,22737FRP820795 (I. G. Farbenindustrie AG); Fr. Pat. 820795 (1937) (Chem. Abstr., 1938, 32, 3422). 23237GEP68065 M. Mugdan (Consortium fur Elektrochemische Industrie); Ger. Pat. 680659 (1937). 21537JA1200 A. L. Henne; J. Am. Chem. Soc., 1937,59, 1200. 212,21837JA1273 F. Beyerstedt and S. M. McElvain; J. Am. Chem. Soc, 1937,59, 1273. 8037JA2266 F. Beyerstedt and S. M. McElvain; J. Am. Chem. Soc, 1937,59,2266. 7437JCS827 J. M. Connolly and G. M. Dyson; J. Chem. Soc, 1937,827. 29737JOC76 M. S. Kharasch.W. G. AlsopandF. R. Mayo; 7. Org. Chem., 1937, 2, 76. 217

38BRP479774 (I. G. Farbenindustrie AG); Br. Pat. 419114 (1938) (Chem. Abstr., 1938, 32, 5226). 23238USP2108606 F. Muller, O. Scherer and W. Schumacher (IG-Farben); US Pat. 2108606 (1938) (Chem.

Abstr., 1938, 32, 2958). 234

39AG457 I. G. Scherer; Angew. Chem., 1939,52,457. 23339GEP740366 K. Vierling, Ger. Pat. 740 366 (1939) (Chem. Abstr., 1945, 39, 2294). 46739JA435 J. H. Simons, T. K. Sloat and A. C. Meunier; / . Am. Chem. Soc, 1939, 61,435. 215, 216, 22139JA2962 J. H. Simons and L. P. Bloch; J. Am. Chem. Soc, 1939,61, 2962. 21239JCS781 P. Dyson and D. L. Hammick; J. Chem. Soc, 1939,781. 2839ZAAC(240)261 W. Hieber, H. Schulten and R. Marin; Z. Anorg. Allg. Chem., 1939, 240, 261. 524

40CB177 M. Linhard and K. Betz; Ber. Dtsch. Chem. Ges., 1940, 73, 177. 439, 45240DOK(26)54 K. A. Kocheshkov, A. N. Nesmeyanov, M. M. Nadj, I. M. Rossinskayaand L. M. Borissova;

Dokl. Akad. Nauk SSSR, 1940, 26, 54 (Chem. Abstr., 1940, 34, 6183). 52240DOK(26)57 K. N. Anisimov and A. N. Nesmeyanov; Dokl. Akad. Nauk SSSR, 1940, 26, 57 (Chem.

Abstr., 1940, 34, 6183). 52240JA3477 J. H. Simons, R. L. Bond and R. E. McArthur; / . Am. Chem. Soc, 1940, 62, 3477. 212, 21740USP2218490 American Cyanamid Co.; US Pat. 2 218490 (1940) (Chem. Abstr., 1941, 35, 1185). 65140ZAAC(245)321 W. Hieber and H. Lagally; Z. Anorg. Allg. Chem., 1940, 245, 321. 524, 525

41CB1667 H. Bohme and R. Marx; Ber. Dtsch. Chem. Ges., 1941,74, 1667. 9041JA3476 A. L. Henne and F. W. Haeckl; J. Am. Chem. Soc, 1941,63, 3476. 241JA3478 A. L. Henne, A. M. Whaley and J. K. Stevenson; / . Am. Chem. Soc, 1941,63, 3478. 16B-41MI 607-01 F. Richter; "Beilsteins Handbuch der Organischen Chemie," 4th edn., Zweites Ergan-

zungswerk, Deutsche Chemische Gesellschaft, Springer-Verlag, Berlin, 1941. 21341ZAAC(248)256 W. Hieber and H. Fuchs; Z. Anorg. Allg. Chem., 1941, 248, 256. 523

42JA1342 E. G. Bohlman and J. E. Willard; J. Am. Chem. Soc, 1942, 64, 1342. 221, 22642JA1825 S. M. McElvain and J. W. Nelson; J. Am. Chem. Soc, 1942, 64, 1825. 70, 7742JA1963 S. M. McElvain and P. M. Walters; J. Am. Chem. Soc, 1942, 64, 1963. 74, 8042JA2515 J. Malkeil and J. P. Mason; J. Am. Chem. Soc, 1942,64,2515. 2742JA2525 S. M. McElvain, H. I. Anthes and S. H. Shapiro; / . Am. Chem. Soc, 1942, 64, 2525. 69, 74, 80

43JA613 S. Winstein and R. E. Buckles;/. Am. Chem. Soc, 1943,65,613. 7143JA2390 D. M. Hubbard and E. W. Scott; J. Am. Chem. Soc, 1943,65,2390. 653B-43MI 603-01 H. W. Post; "The Chemistry of the Aliphatic Ortho Esters," Reinhold, New York, 1943. 68, 77, 8143MI616-01 W. Hieber and H. Stallman; Z. Electrochem., 1943,49,288. 52443OSC(2)462 E. D. Amstutz and R. R. Myers; Org. Synth., Coll. Vol., 1943, 2, 462. 50643ZAAC(251)96 H. Lagally; Z. Anorg. Allg. Chem., 1943, 251, 96. 525

44JCS74 W. S. Rapson, D. H. Saunder and E. T. Stewart; J. Chem. Soc, 1944, 74. 2544JOC419 F. C. Schmidt, C. E. Sunderling and Q. P. Cole; J. Org. Chem., 1944,9, 419. 26144MI 614-01 S.-C. Li; J. Chin. Chem. Soc, 1944,11, 14 (Chem. Abstr., 1945, 39, 1099). 40944USP2351390 A. F. Benning and J. D. Park; US Pat. 2351390 (1944) (Chem. Abstr., 1944, 38, 5228). 21444USP2365981 J. B. Tindall (Commercial Solvents Corp.); US Pat. 2365981, 1944 (Chem. Abstr., 1946, 40,

3126). 241

45BAU364 M. I. Kabachnik and P. A. Rossiiskaya; Bull. Acad. Sci. USSR, Div. Chim. Set, 1945, 364(Chem. Abstr., 1946,40, 4688). 455

45JA650 S. M. McElvain and B. Fajardo-Pinzon; J. Am. Chem. Soc, 1945, 67, 650. 7445JA1642 H. Soroos and J. B. Hinkamp; J. Am. Chem. Soc, 1945, 67, 1642. 216, 21745JA2079 R. Duschinsky and L. A. Dolan; J. Am. Chem. Soc, 1945,67,2079. 50845JCS864 G. D. Buckley, H. A. Piggott and A. J. E. Welch; J. Chem. Soc, 1945, 864. 43945USP2389153 J. D. Kendall; US Pat. 2389 153 (1945) (Chem. Abstr., 1946, 40, 1540). 84

46JA968 T. J. Brice, W. H. Pearlson and J. H. Simons; J. Am. Chem. Soc, 1946, 68, 968. 21846JA1672 J. H. Simons, D. F. Herman and W. H. Pearlson; J. Am. Chem. Soc, 1946, 68, 1672. 41946JA1922 S. M. McElvain, R. E. Kent and C. L. Stevens; J. Am. Chem. Soc, 1946, 68, 1922. 70, 8046MI 616-01 R. P. Lastovskii; J. Appl. Chem. (USSR), 1946, 19,440. 500

References 745

46RTC53 H. J. Backer; Reel. Trav. Chim. Pays-Bas, 1946,65,53. 91,27546ZN(B)518 A. M. Paquin; Z. Naturforsch., Teil B, 1946,1,518. 48446ZOB1521 G. Kamai and L. P. Egorova; Zh: Obshch. Khim., 1946, 16, 1521 {Chem. Abstr., 1947, 41,

5439). 242

47CI(L)427 W. B. Whalley; Chem. Ind. {London), 1947,66,427. 21747IEC404 E. T. McBee, H. B. Hass, L. W. Frost and Z. D. Welch; Ind. Eng. Chem. Res., 1947, 39,404. 220, 22547JA947 E. T. McBee, R. O. Bolt, P. J. Graham and R. F. Tebbe; / . Am. Chem. Soc, 1947, 69, 947. 22047JA1100 M. S. Kharasch, E. V. Jensen and W. H. Urry; / . Am. Chem. Soc, 1947, 69, 1100. 547JA1723 B. B. Owen, J. English Jr., H. G. Cassidy and C. V. Dundon; / . Am. Chem. Soc, 1947, 69,

1723. 52247JA1820 A. L. Henne and P. Trott; J. Am. Chem. Soc, 1947,69, 1820. 1647JA1833 R. E. Dunbar and E. P. Painter; J. Am. Chem. Soc, 1947,69, 1833. 59647JA3150 R. Duschinsky, L. A. Dolan, L. O. Randall and G. Lehmann; / . Am. Chem. Soc, 1947, 69,

3150. 50847JCS674 F. R. Atherton and A. R. Todd; J. Chem. Soc, 1947,674. 221

48JA383 H. Adkins and G. Krsek; J. Am. Chem. Soc, 1948,70,383. 52448JA1968 J. L. Hutson and T. H. Norris; J. Am. Chem. Soc, 1948,70, 1968. 41548JA2268 W. E. Mochel, C. L. Agre and W. E. Hanford; J. Am. Chem. Soc, 1948, 70, 2268. 8048JA3986 K. B. Kellogg and G. H. Cady; J. Am. Chem. Soc, 1948, 70, 3986. 23148JCS687 J. D. Kendall and J. R. Majer; / . Chem. Soc, 1948,687. 8448JCS2183 H. J. Emeleus and J. F. Wood; J. Chem. Soc, 1948,2183. 409,419,42248JCS2188 A. A. Banks, H. J. Emeleus, R. N. Haszeldine and V. Kerrigan; J. Chem. Soc, 1948, 2188.

212, 214, 217, 218, 219, 220, 222, 225, 226, 24648JOC265 H. Tieckelmann and H. W. Post; J. Org. Chem., 1948,13, 265. 296, 297, 308B-48MI607-01 E. H. Huntress; "Organic Chlorine Compounds," John Wiley & Sons, New York, 1948,

p. 576. 21448RTC884 H. J. Backer and G. J. de Jong; Reel. Trav. Chim. Pays-Bas, 1048, 67, 884. 9048RTC894 H. J. Backer; Reel. Trav. Chim. Pays-Bas, 1948,67,894. 307

49AG183 H. Hopff and H. Ohlinger; Angew. Chem., 1949,61, 183. 44349AK(1)231 E. Samen; Ark. Kemi, 1949,1,231. 9149DOK(68)515 B. A. Arbuzov and T. G. Shavsha; Dokl. Akad. Nauk SSSR, 1949, 68, 515 {Chem. Abstr.,

1950, 44, 392). 29749JA298 A. L. Henne and W. G. Finnegan; J. Am. Chem. Soc, 1949, 71, 298. 1649JA2297 R. A. Henry and W. M. Dehn; J. Am. Chem. Soc, 1949,71, 2297. 50449JA2499 T. J. Brice, W. H. Pearlson and J. H. Simons; J. Am. Chem. Soc, 1949, 71, 2499. 21849JCS2856 R. N. Haszeldine; J. Chem. Soc, 1949,2856. 21949JCS2948 H. J. Emeleus and R. N. Haszeldine; J. Chem. Soc, 1949, 2948. 249JCS2953 H. J. Emeleus and R. N. Haszeldine; J. Chem. Soc, 1949,2953. 24649JOC747 D. D. Coffman, M. S. Raasch, G. W. Rigby, P. L. Barrick and W. E. Hanford; J. Org.

Chem., 1949,14, 747. 249LA(562)229 A. Bertho; Justus Liebigs Ann. Chem., 1949, 562, 229. 10549MI 603-01 R. Barre and B. Ladouceur; Can. J. Res., 1949, B27, 61 {Chem. Abstr., 1949,43, 5365). 7749MI 607-01 J. H. Simons; / . Eleclrochem. Soc, 1949, 95, 47 {Chem. Abstr., 1949, 43, 2876). 21449USP2473993 W. F. Gresham and J. V. E. Hardy; US Pat. 2473993 (1949) {Chem. Abstr., 1949,43,9398). 52449USP2476263 C. H. McKeever; US Pat. 2476263 (1949) {Chem. Abstr., 1949, 43, 9397). 52449USP2477553 C. H. McKeever; US Pat. 2 All 553 (1949) {Chem. Abstr., 1949, 43, 8107). 52449USP2477554 C. H. McKeever; US Pat. 2477 554 (1949) {Chem. Abstr., 1949, 43, 8108). 524

50ACS397 E. Samen; Acta Chem. Scand., 1950,4,397. 9150DOK(70)231 B. A. Arbusov and E. K. Yuldasheva; Dokl. Akad. Nauk SSSR, 1950,70, 231 {Chem. Abstr.,

1950,44, 3 759). 7850IS37 R. E. McArthur and J. H. Simons; Inorg. Synth., 1950,3,37. 21650IS156 B. B. Owen, J. English, Jr., H. G. Cassidy and C. V. Dundon; Inorg. Synth., 1950, 3, 156. 52250IS171 H. F. Priest; Inorg. Synth., 1950,3, 171. 21250JA1661 S. M. McElvain and J. T. Venerable; J. Am. Chem. Soc, 1950, 72, 1661. 6950JA1888 R. J. Slocombe, E. E. Hardy, J. H. Saunders and R. L. Jenkins; / . Am. Chem. Soc, 1950,

72, 1888. 44350JA2213 J. Harmon, T. A. Ford, W. E. Hanford and R. M. Joyce; J. Am. Chem. Soc, 1950,72, 2213. 550JA3529 C. M. Buess and N. Kharasch; J. Am. Chem. Soc, 1950,72,3529. 23350JA3642 K. E. Rapp, R. L. Pruett, J. T. Barr, C. T. Bahner, J. D. Gibson and R. H. Lafferty, Jr.; J.

Am. Chem. Soc, 1950, 72, 3642. 4650JA5012 E. D. Bergmann, D. Ginsberg and D. Lavie; J. Am. Chem. Soc, 1950, 72, 5012. 2550JA5329 N. S. Marans and R. P. Zelinski; J. Am. Chem. Soc, 1950,72, 5329. 14550LA(566)229 H. Bestian; Justus Liebigs Ann. Chem., 1950,566, 229. 48350RTC1223 H. J. Backer and H. Bos; Reel. Trav. Chim. Pays-Bas, 1950, 69, 1223. 11450TFS295 F. S. Dainton and K. J. Irvin; Trans. Faraday Soc, 1950,46,295. 21550USP2500388 J. H. Simons (Minnesota Mining & Mfg. Co.); US Pat. 2500388 (1950) {Chem. Abstr., 1950,

44,5236). 22950USP2531372 H. Waterman (Minnesota Mining & Mfg. Co.); US Pat. 2521212 {1950) {Chem. Abstr., 1951,

45, 1705). 218

746 References

51JA1864 L. C. King and R. J. Hlavacek; J. Am. Chem. Soc, 1951,73, 1864. 59651JA2233 S. M. McElvain and B. E. Tate; J. Am. Chem. Soc, 1951,73, 2233. 7051JA2461 M. Hauptschein and A. V. Grosse; / . Am. Chem. Soc, 1951,73, 2461. 21951JA3796 J. H. Saunders, R. J. Slocombe and E. E. Hardy; J. Am. Chem. Soc, 1951, 73, 3796. 42551JA3807 S. M. McElvain, S. B. Mirviss and C. L. Stevens; J. Am. Chem. Soc, 1951, 73, 3807. 7451JA5168 R. G.Jones; J. Am. Chem. Soc, 1951,73,5168. 3951JCS584 R. N. Haszeldine; J. Chem. Soc, 1951,584. 32,216,218,21951JCS1145 B. R. Brown, D. L. Hammick and B. H. Thewlis; J. Chem. Soc, 1951, 1145. 2851JOC1829 A. F. McKay and R. O. Braun; X Org. Chem., 1951,16, 1829. 50851MI 614-01 H. J. Schumacher; Anales de la Asociucibn Quimica Argentina, 1951, 39, 159 (Chem. Abstr.,

1953, 46, 5439). 40951M1008 R. Riemschneider; Monatsh. Chem., 1951,82, 1008. 2751OSC(1)258 W. E. Kaufmann and E. E. Dreger; Org. Synth., Coll. Vol. 1, 1951, 258. 6851RTC733 H. J. Backer; Reel. Trav. Chim. Pays-Bos, 1951,70,733. 11451RTC892 H. J. Backer; Reel. Trav. Chim. Pays-Bas, 1951,70, 892. 11451RTC917 H. L. Klopping and G. J. M. van der Kerk; Reel. Trav. Chim. Pays-Bas, 1951, 70, 917. 56051RTC949 H. L. Klopping and G. J. M. van der Kerk; Reel. Trav. Chim. Pays-Bas, 1951,70, 949. 56051USP2553518 D. E. Lake and A. A. Asadorian (The Dow Chemical Company); US Pat. 2553518 (1951)

(Chem. Abstr., 1952, 46, 2561). 21551USP2553800 J. P. West and L. Schmerling (Universal Oil Products Co.); US Pat. 2553800 (1951) (Chem.

Abstr., 1952,46,2561). 221

52CB901 H. Schlenk; Chem. Ber., 1952,85,901. 2752CB949 B. Witkop, J. B. Patrick and H. M. Kissman; Chem. Ber., 1952, 85, 949. 10852HOU(8)84 S. Petersen; Methoden Org. Chem. (Houben-Weyt), 1952,8,84. 41352HOU(8)101 S. Petersen; Methoden Org. Chem. (Houben-Weyl), 1952,8, 101. 42452JA554 E. R. Alexander and H. M. Busch; J. Am. Chem. Soc, 1952, 74, 554. 7852JA848 M. Hauptschein, C. S. Stokes and A. V. Grosse; J. Am. Chem. Soc 1952, 74, 848. 3252JA849 M. Hauptschein, R. L. Kinsman and A. V. Grosse; J. Am. Chem. Soc. 1952,74, 849. 3252JA1347 M. Hauptschein, E. A. Nodiffand A. V. Grosse; J. Am. Chem. Soc, 1952, 74, 1347. 21852JA1418 F. B. Smith and C. A. Kraus; J. Am. Chem. Soc, 1952,74, 1418. 18552JA1974 M. Hauptschein, C. S. Stokes and A. V. Grosse; / . Am. Chem. Soc. 1952, 74, 1974. 3252JA2292 J. D. Park, D. M. Griffin and J. R. Lacher; J. Am. Chem. Soc, 1952, 74, 2292. 3652JA3594 W. E. Truce, G. H. Birum and E. T. McBee; J. Am. Chem. Soc, 1952,74, 3594. 16, 44, 45, 23452JA3855 B. Witkop and J. B. Patrick; J. Am. Chem. Soc, 1952,74, 3855. 10852JA4582 L. F. Cason and H. G. Brooks; J. Am. Chem. Soc, 1952,74,4582. 19252JA5792 G. A. Silvey and G. H. Cady; J. Am. Chem. Soc, 1952,74, 5792. 41052JCS2198 G. A. R.Brandt, H. J. Emeleus and R. N. Haszeldine; J. Chem. Soc, 1952, 2198. 23352JCS3490 R. N. Haszeldine; J. Chem. Soc, 1952,3490. 552JCS4259 R. N. Haszeldine; J. Chem. Soc, 1952, 4259. 213, 216, 220, 223, 224, 225, 226, 227, 22852JCS4423 R. N. Haszeldine; J. Chem. Soc, 1952,4423. 252MI 601-01 F. Smith, M. Stacey, J. C. Tatlow, J. K. Dawson and B. R. J. Thomas; J. Appl. Chem., 1952,

2,97. 952MI 607-01 L. I. Zakharkin; Sint. Org. Soedin. Sbornik, 1952, 2, 18 (Chem. Abstr., 1954,48, 547). 22152MI 607-02 O. O. Orazi, N. M. I. Mercere, R. A. Corral and J. Meseri; An. Asoc. Quim. Arg., 1952, 40,

91 (Chem. Abstr., 1953, 47, 8667). 22152RTC409 H. J. Backer; Reel. Trav. Chim. Pays-Bas, 1952,71,409. 30752RTC1071 H. J. Backer and E. Westerhuis; Reel. Trav. Chim. Pays-Bas, 1952, 71, 1071. 30152USP2592565 M. T. Harvey; US Pat. 2 592 565 (1952) (Chem. Abstr., 1953, 47, 601). 50852USP2616927 E. A. Kauck and J. H. Simons (Minnesota Mining & Mfg. Co.); US Pat. 2616927 (1952)

(Chem. Abstr., 1953, 47, 8771). 21452ZOB2216 L. B. Yagupol'skii and A. I. Kiprianov; Zhur. Obshch. Khim., 1952, 22, 2216 (Chem. Abstr.,

1953,47,4771). 232

53CB557 H. Brintzinger and S. M. Langheck; Chem. Ber., 1953,86,557. 23353CB790 H. Stetter and K. H. Steinacker; Chem. Ber., 1953,86,790. 8053CJC896 J. P. Picard and A. F. McKay; Can. J. Chem., 1953,31, 896. 50853JA671 C. W. Whitehead; J. Am. Chem. Soc, 1953,75,671. 10453JA1120 A. F. McKay, W. G. Hatton and G. W. Taylor; J. Am. Chem. Soc, 1953,75, 1120. 50853JA1668 D. S. Tarbell and A. H. Herz; / . Am. Chem. Soc, 1953,75, 1668. 83,8453JA3987 S. M. McElvain and C. L. Aldridge; J. Am. Chem. Soc, 1953, 75, 3987. 7053JA4053 F. L. Scott, D. G. O'Donovan and J. Reilly; J. Am. Chem. Soc, 1953, 75, 4053. 64153JA4582 I. B. Douglass and C. E. Osborne; J. Am. Chem. Soc, 1953, 75, 4582. 25553JCS922 R. N. Haszeldine; J. Chem. Soc, 1953,922. 5,22153JCS1063 J. F. Ellis and W. K. R. Musgrave; J. Chem. Soc, 1953, 1063. 22053JCS1548 R. N. Haszeldine and K. Leedham; J. Chem. Soc, 1953, 1548. 253JCS2075 R. N. Haszeldine; J. Chem. Soc, 1953,2075. 24153JCS2372 A. F. Clifford, H. K. El-Shamy, H. J. Emeleus and R. N. Haszeldine; / . Chem. Soc, 1953,

2372. 21453JCS3219 R. N. Haszeldine and J. M. Kidd; J. Chem. Soc, 1953, 3219. 232, 23653JCS3607 R. N. Haszeidine and E. G. Walaschewski; J. Chem. Soc, 1953, 3607. 6453JCS3761 R. N. Haszeldine; J. Chem. Soc, 1953,3761. 5

References 1A1

53JGU229 M. S. Malinovsky and N. M. Medyansteva; / . Gen. Chem. USSR (Engl. Trans!.), 1953, 23,229. 429

53JOC292 R. A. Zingaro, F. C. Bennett, Jr. and G. W. Hammar; J. Org. Chem., 1953,18, 292. 59653JOC328 M. S. Kharasch, E. Simon and W. Nudenberg; J. Org. Chem., 1953,18, 328. 553LA(581)133 H. Bohme and H. J. Gran; Justus Liebigs Ann. Chem., 1953, 581, 133. 44, 9153LA(582)116 W. Reppe; Justus Liebigs Ann. Chem., 1953, 582, 116. 52453MI 603-01 T. R. Rix and J. F. Arens; Koninkl. Ned. Akad. Wetenschap., Proc, 1953, B56, 364 {Chem.

Abstr., 1955, 49, 2299). 7453USP2639301 R. P. Ruh and R. A. Davis (Dow Chem. Co.); US Pat. 2639301 (1953) (Chem. Abstr., 1954,

48,3382). 22653USP2639302 R. P. Ruh and R. A. Davis (Dow Chem. Co.); US Pat. 2639302 (1953) (Chem. Abstr., 1954,

48,3382). 22353USP2647933 J. D. La Zerte, W. H. Pearlson and E. A. Kauck (Minnesota Mining & Mfg. Co.); US Pat.

2647933 (1953) (Chem. Abstr., 1954, 48, 7622). 32, 21853USP2658086 R. P. Ruh and R. A. Davis (Dow Chem. Co.); US Pat. 2658086 (1953) (Chem. Abstr., 1954,

48, 12787). 22653USP2658927 W. Kwasnik (Farbenfabr. Bayer AG); US Pat. 2658927 (1953) (Chem. Abstr., 1954, 48,

12787). 217

54CB205 H. StetterandK. H. Steinacker; C/zem. Ber., 1954,87,205. 8054JA474 O. R. Pierce, E. T. McBee and G. F. Judd; J. Am. Chem. Soc, 1954, 76, 474. 24454JA3831 E. O. Brimm, M. A. Lynch Jr. and W. J. Sesny; J. Am. Chem. Soc, 1954, 76, 3831. 52354JA5141 D. R. Husted and W. L. Kohlhase; J. Am. Chem. Soc, 1954, 76, 5141. 21854JA5736 S. M. McElvain, E. R. Degginger and J. D. Behun; J. Am. Chem. Soc, 1954, 76, 5736. 7554JCS912 J. Jander and R. N. Haszeldine; J. Chem. Soc, 1954,912. 24154JCS919 J. Jander and R. N. Haszeldine; 7. Chem. Soc, 1954,919. 44154JCS923 R. N. Haszeldine and B. R. Steele; J. Chem. Soc, 1954,923. 254JCS3598 F. W. Bennett, H. J. Emeleus and R. N. Haszeldine; / . Chem. Soc, 1954, 3598. 24254JGU885 L. M. Yagupol'skii and M. S. Marenets; J. Gen. Chem. USSR (Engl. Transl.), 1954, 24, 885. 23254JOC1278 L. F. Cason and H. G. Brooks; J. Org. Chem., 1954,19, 1278. 19254LA(587)226 H. P. Kaufmann, A. Seher and P. Hagedorn; Justus Liebigs Ann. Chem., 1954, 587, 226. 6954USP2694739 J. R. Pailthorp (du Pont de Nemours & Co); US Pat. 2694739 (1954) (Chem. Abstr., 1955,

49, 12526). 217

55AG374 H. Meerwein; Angew. Chem., 1955,67,374. 7155CI(M)6 G. Natta, R. Ercoli and S. Castellano; Chim. Ind. (Milan), 1955,37,6. 52455CRV181 D. C. Schroeder; Chem. Rev., 1955,55, 181. 569,57555DOK(105)100 L. M. Yagupol'skii, Dokl. Akad. Nauk SSSR, 1955,105,100 (Chem. Abstr., 1956,50,11270). 22955JA509 W. von E. Doering and L. K. Levy; J. Am. Chem. Soc, 1955, 77, 509. 82, 83, 9155JA768 P. Tarrant and A. M. Lovelace; J. Am. Chem. Soc, 1955,77,768. 555JA1899 I. B. Douglass and F. J. Marascia; J. Am. Chem. Soc, 1955, 77, 1899. 22955JA2479 H. R. Al-Kazimi, D. S. Tarbell and D. Plant; J. Am. Chem. Soc, 1954, 77, 2479. 54055JA2869 I. S. Bengelsdorf and L. B. Barron; J. Am. Chem. Soc, 1955, 77, 2869. 24255JA3099 S. Nakanishi, T. C. Meyers and E. V. Jensen; J. Am. Chem. Soc, 1955, 77, 3099. 42255JA3801 R. M. Roberts, T. D. Higgins, Jr. and P. R. Noyes; / . Am. Chem. Soc, 1955, 77, 3801. 7855JA3951 R. A. Friedel, I. Wender, S. L. Shufler and H. W. Sternberg; J. Am. Chem. Soc, 1955, 77,

3951. 52455JA5033 S. Nakanishi, T. C. Meyers and E. V. Jensen; J. Am. Chem. Soc, 1955, 77, 5033. 42155JA5601 S. M. McElvain and G. R. McKay; J. Am. Chem. Soc, 1955, 77, 5601. 7555JA6644 H. Gilman and R. G. Wilder; J. Am. Chem. Soc, 1955,77,6644. 6955JCS1881 D. A. Barr and R. N. Haszeldine; J. Chem. Soc, 1955, 1881. 60455JCS2532 D. A. Barr and R. N. Haszeldine; J. Am. Chem. Soc, 1955,2532. 23855JCS3871 R. N. Haszeldine and J. M. Kidd; J. Chem. Soc, 1955,3871. 53455JOC1573 J. G. Erickson; 7. Org. Chem., 1955,20, 1573. 7055MI 618-01 S. Kodama, S. Fukushima and S. Nose; Bull. Chem. Soc Jpn., 1955, 58, 211 (Chem. Abstr.,

1955,49,13 685). 58055OSC(3)773 R. L. Frank and P. V. Smith; Org. Synth., Coll. Vol., 1955, 3, 773. 57255OSC(3)803 P. Liang; Org. Synth. Coll. Vol., 1955,3, 803. 36555USP2704776 J. D. LaZerte, W. H. Pearlson and E. A. Kauck; US Pat. 2704776 (1955) (Chem. Abstr.,

1956,50,2650). 21855USP2709184 E. L. Muetterties (du Pont de Nemours & Co.); US Pat. 2709184 (1955) (Chem. Abstr., 1956,

50,6498). 217,220,22555USP2709186 M. W. Farlow and E. L. Muetterties (du Pont de Nemours & Co.); US Pat. 2709186 (1955)

(Chem. Abstr., 1956, 50, 6499). 21255USP2709187 M. W. Farlow and E. L. Muetterties (du Pont de Nemours & Co.); US Pat. 2709187 (1955)



(Chem. Abstr., 1956, 50, 6499). 21255ZAAC(282)345 K. Ziegler, K. Nagel and M. Patheiger; Z. Anorg. Allg. Chem., 1955, 282, 345. 206

56ACS1006 B. Smith; Ada Chem. Scand., 1956, 10, 1006. 78,79

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