NEW REACTIONS IN ORGANOSELENIUM CHEMISTRY...of organoselenium chemistry, covering the literature up...
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1. NEW REACTIONS IN ORGANOSELENIUM CHEMISTRY a thesis presented by ANDREW GEORGE BREWSTER in partial fulfilment of the requirements for the award of the degree of DOCTOR OF PHILOSOPHY OF THE UNIVERSITY OF LONDON WHIFFEN LABORATORY ) CHEMISTRY DEPARTMENT, IMPERIAL (ALLEGE) LONDON SW7 2AY AUGUST) 1977,
Transcript of NEW REACTIONS IN ORGANOSELENIUM CHEMISTRY...of organoselenium chemistry, covering the literature up...
1.
NEW REACTIONS IN ORGANOSELENIUM CHEMISTRY
a thesis presented by
ANDREW GEORGE BREWSTER
in partial fulfilment of the requirements
for the award of the degree of
DOCTOR OF PHILOSOPHY
OF THE
UNIVERSITY OF LONDON
WHIFFEN LABORATORY)
CHEMISTRY DEPARTMENT,
IMPERIAL (ALLEGE)
LONDON SW7 2AY
AUGUST) 1977,
2.
ACKNOWLEDGEMENTS
I thank Professor Sir Derek Barton, F.R.S., for his encourage-
ment, guidance and tolerance throughout the course of this work.
I also thank Dr. S.V. Ley for his enthusiasm and assistance,
Mr. K.I. Jones and his staff for the microanalytical service, Mrs. Lee
for the mass-spectrometry service, Mr. T. Adey for technical assistance,
Mrs. Day for her kindness and cooperation in the stores and Miss
Maria C. Serrano for her patience and helpfulness during the typing
of this Thesis.
Finally, I wish to thank the Science Research Council for a student-
ship for the period of this research.
Andrew G. Brewster,
Whiffen Laboratory,
August, 1977.
3.
ABSTRACT
Reviews of some interesting new reactions in organoselenium
chemistry and of the synthesis of ortho-quinones are presented and
the properties and reactions of benzeneseleninic anhydride are
summarised.
Benzeneseleninic anhydride has been used to oxidise simple
phenols, the major products being the para-hydroxydienones, eg. (A)
OH
OH
(A)
Reaction of the anhydride with the phenolate anion did not
noticeably affect the results.
Oxidation of many phenols with benzeneseleninic anhydride at 50°
gives ortho-quinones in yields of 50-70%. The procedure is almost
exclusively ortho-selective and represents the best method yet developed
for the conversion of phenols to o-quinones. The previously unreported
compound, 3-methyl-6-isopropyl-1,2-benzoquinone (B) was prepared in this
manner but some simple phenols, eg. 2,4-xylenol, give complicated
mixtures of products from which no quinones can be isolated.
4.
OH OSePh
(B)
(C)
Attempts to isolate or trap likely intermediates of type (C) were
unsuccessful.
Treatment of some catechols and quinols with the anhydride at 50°
gave the corresponding quinones in high yield.
The reaction of phenols with hexamethyldisilazane and the anhy-
dride to give selenoimines, (D), has been examined. Several selenoimines
have been prepared and the mildness of the procedure has been demonstrated.
Compound (D) has also been the subject of an X-ray crystallographic study.
NSePh 0 SiMe / 3 Ph —Se —N
Si Me3
(o)
(E)
The mechanism of selenoimine formation has been studied but attempts
to synthesise potential reactive intermediates, eg. (E), have failed.
A redox titration study of benzeneseleninic anhydride oxidations
has enabled the relative rates of reaction to be qualitatively estimated
5.
and has given support to mechanistic conclusions reached previously.
A series of benzylic alcohols was smoothly oxidised to the
corresponding carbonyl compounds in high yield using benzeneseleninic
anLydride.
6.
CONTENTS
Page
Acknowledgements 2
Abstract 3
Review 7
New Reactions in Organoselenium Chemistry 7
The Synthesis of Ortho-Quinones 27
References 34
Benzeneseleninic Anhydride; Previous Work 38
References 47
Results and Discussion 49
(1) Hydroxylation of Phenols with Benzene- 49 seleninic Anhydride
(2) Conversion of Phenols to Quinones 55
(3) Conversion of Catechols and Quinols to 65 Quinones
(4) Formation of Selenoimines 66
(5) Mechanism of Selenoimine Formation 81
(6) Redox- Titration Study of Benzeneseleninic 84 Anhydride Oxidations
(7) Oxidation of Benzylic Alcohols with 93 Benzeneseleninic Anhydride
Experimental 95
References 125
7.
NEW REACTIONS IN ORGANO-SELENIUM CHEMISTRY
An exhaustive review1 of organoselenium chemistry, covering the
literature up to the end of 1972 was recently published. This section
examines some of the more significant work which has appeared since that
date, but is not meant to be a comprehensive survey.
1- Selenoxide Eliminations
Selenoxides are preparedby oxidation of selenides2, usually with
ozone or peracid. The products are stable at room temperature unless there
is a s-hydrogen atom present in the molecule, in which case a facile elimi-
nation of the selenenic acid takes place to yield the olefin.
0 t.
H Se ,/
13 RCH2CH2SeR --------+ R--CH--CH2 ----4 RCH==CH2+ RSeOH
This elimination process was first observed by Jones3 et al. who found
that both diastereomers of the 6-phenylseleninocholestane derivative (1),
which were separable at low temperature (-500), gave A6-cholestene on warming
to room temperature. At 0°C however, one isomer was inert whilst the other
gave the olefin after four hours.
,c
RT
0.)
Ph Me
.E--/ H
• (A) electrons reversed]
[(B) as for (A) with Ph and lone pair of
0 (21.1 3 (z) (E)
Ph 15% 42%
H3 H202/THF
PhSe
H
(2)
PhSe
H
,Ph
C H3 C H3
(3)
13% 45%
8.
It was deduced that a syn-elimination process was taking place and
the rate difference between the two isomers was attributed to steric
crowding in the transition-state. Thus in transition-state (A), from the
(S)-isomer, there is less compression so the elimination is rapid. In the
case of the (R)-isomer the steric factor makes the cyclic transition-state
(B) harder to attain, so the elimination is slower.
Further evidence for the syn-nature of the elimination was obtained
from a study4 of the ratios of olefins produced by selenoxide elimination
after oxidation of selenides (2) and (3). As shown below, formation of the
2-phenyl-2-butenes occurred by stereospecific syn-elimination. The erythro-
isomer (2) gave only the (Z)-olefin and the threo-isomer (3) gave only the
(E)-olefin, while the major product in both cases was the 3-phenyl-1-butene.
PRODUCTS
Ph> P h Ph
N
25°, 2.5 h
Ac
IllithSeBr,Et20, 0o (1) Ag02CCF3
(2) Hydrolysis
9.
The ease with which selenoxides undergo hydration has also been
demonstrated Treatment of selenide (4) with aqueous hydrogen peroxide
solution at room temperature gave only 6% of the olefin after sixteen
hours. On addition of anhydrous magnesium sulphate, however, the olefin was
produced in 77% yield after only two and a half hours. It would appear
that, in this case, the hydrate is actually the predominant species in
solution.
1:111
RCH2CH2SePh THF RCH CH RCH CH SePh----R
70% H202 2 21 2 21
(4) OH -0
(R = n-decyl)
The phenomenon of selenoxide fragmentation at, or below, room temp-
erature was applied to the introduction of a,6-unsaturation into ketones.5
Thus treatment of the enol acetate of cyclohexanone with silver trifluoro-
acetate and benzeneselenenyl bromide in ether at 0°, followed by hydrolysis,
gave the a-phenylselenoketone in 70% yield. Oxidation with sodium periodate
gave the enone in 92% yield.
Sharpless and Lauer6
developed a route to allylic alcohols via the
nucleophilic action of the benzeneselenolate anion on an epoxide to give
6-hydroxyalkyl phenylselenides. Oxidation and elimination then gave the
(E)-alcohol in high yield. It was noted that the elimination always
SePh
1)H202'0-25° HO-_,./\,/
2h, RT
EtOH
10.
appears to occur away from the hydroxyl group.
SePh
B-HydroXyalkyl phenylselenides have also been obtained by the addition
of benzeneselenenyl trifluoroacetate to olefins, followed by hydrolysis.7
PhSeOCOCF3 0 KOH 0 EtOH
SePh
The reaction is not highly regioselective for unsymmetrical olefins
but in all cases studied the addition was stereospecific. Cis and trans-
butenes gave different products while cyclohexene gave a single adduct with
both substituents in an equatorial environment.
Benzeneselenenyl bromide and acetate undergo electrophilic trans-
1,2-addition to olefins and this has been used8 as a basis for a new route
to allylic acetates and ethers. For example, oxidation of the adduct (5)
gave predominantly the allylic derivative since, as noted previously,
elimination shows a marked preference for occurring away from the functional
group, (Interestingly, when X = Cl,elimination occurs equally in both
directions.) Solvolysis of the adduct (5) followed by oxidation gave the
allylic ethers.
ROM SePh CI:
(5) 'X
+ PhSeX
X = Br, Cl, OAc
+
02/THF
OR
11.
(MAJOR)
Treatment of ketones and aldehydes with benzeneselenenyl chloride
has been shown9 to give the a-phenylseleno-derivatives in high yield.
Methods for the introduction of the selenide function a-to an ester group
were also developed and oxidation of the product yielded the a,8-unsaturated
compounds.
R SePh
0
R\
X = H, alkyl or
o
0-alkyl
a-Phenylseleno-carbonyl compounds have been obtained10 by the low
temperature (-78°) reaction between benzeneselenenyl bromide and lithium
enolates. Oxidation of the product yielded the unsaturated compounds by
an even milder procedure. In this manner, 1,4-dipheny1-1-butanone (6)
SePh
12.
'was converted to (7) in 84% yield. Less than 0.5% of the more stable
phenyl-conjugated isomer (8) was formed.
0 Ph
Ph
Ph
0 Ph
\ Ph
Ph
(6)
(7) (8)
Reich11 recognised that the necessity for achieving a cyclic transition-
state in the selenoxide elimination may impose conflicting conformational
demands on cyclic systems and an investigation was carried out into why
only a limited range of cyclic enones (five and six membered rings) had
been prepared. It was concluded that in many cases a Pummerer-type reaction
was occurring to give unwanted byproducts.
1)K 0 SePh
t_0
H+
SePh 1-1 t0H
€Ph
6H2 +0 H2
This reaction depends on the acidity of proton Ha. If this is a-
to a carbonyl group the reaction is facile. Thus in the oxidation of
selenide (9) the desired product (10) is obtained in low yield and the
byproducts (11) and (12) may be directly attributable to the Pummerer
reaction.
13.
Se Ph (iii) (iv)
ePh
(i) LiNR2
( 9)
(10),48%. (11),17% (12),9%
(ii) PhSeBr
(iii) 03, -78°
(iv) 25°
However the ketal (13) undergoes oxidation and elimination to give
enone ketal (14) in good yield, since the ketal function does not enhance
the acidity of the a-proton.
1---\ 0 o 0
Se Ph ((i;20H )2 SePh H202 ■„;><
Ts0H
(9)
(13),81% (14),80%
Using this procedure 8-dicarbonyl compounds may be converted to
enediones11, a transformation which is difficult using classical methods.
Thus 2-carboethoxycyclohexanone gave the alkenone in 78% overall yield.
14.
Owing to the mild reaction conditions the non-enolised ft-dicarbonyl
enones were formed exclusively in all cases even though a number of these
systems are known to be significantly, or even predominantly, enolic at
eLyilibrium12 .
1 Grieco3 et al. developed a route to a-methylene lactones involving
the stereospecific alkylation of the lactone enolate. In the case of the
trans-fused y-butyrolactone (15), conversion to the trans-a-methylene-y-
butyrolactone (16) was readily achieved with complete exclusion of the endo-
cyclic isomer (17).
(15)
(17)
H
Me
This example provides further support for the involvement of a cyclic
transition-state during selenoxide elimination.
A study14 of the nucleophilic action of anions a- to a selenoxide
showed that two different reactions were possible (pathway (a) or (b),
below) depending on the direction of elimination.
) > < (a) OH
Ph
Ph.
15.
H6
x
0 PhSe
0 PhSe
Ha b/
Ha Li
b
In order to block one of these pathways it was necessary to choose
systems containing either no Ha or no Hb. Thus with benzaldehyde, anion
(18) gave the path (a) product, the net reaction being therefore equivalent
to the operation of a vinyl anion.
Reaction of anion (19), which contains no 8-hydrogen atom, with
cinnamyl bromide gave the path (b) type product only.
0 II
PhSe + Ph Br
(19)
(b)
,N̂ Ph
75%
16.
Since the selenide precursor to (19) is prepared from the halide,
this reaction is equivalent to a coupling of two halides to give an
olefin.
In a full paper, Reich15 has summarised his work on the conversion of
ketones to enones using selenoxide elimination. The best methods for
initial phenylselenenylation are discussed and several procedures for
subsequent oxidation and elimination are also presented.
In addition to the Pummerer-type byproducts, a further side reaction
was detected involving the reaction between the enolate (or enol) of
a-phenylselenino ketones and selenenylating species formed during the
disproportionation of benzeneselenenic acid. Hence the selenide (21)
was shown by means of cross-over experiments to be derived from (20).
PhSeX
(21)
(20)
The most likely selenenylating agent was thought to be PhSeOSePh
but this could not be isolated.
Direct introduction of the benzeneseleninyl group a- to the carbonyl
function, followed by syn-elimination in one step was possible but the
yields were variable and frequently lower than those obtained by the two-
step procedure,
01
0
v,c.,Se Ph II 0
17.
Since benzeneseleninyl chloride is extremely hygroscopic it is
recommended that this method only be used when the normal selenide
oxidation procedure fails because of competing or preferential oxidation
elsewhere in the molecule.
A study16
has been made of the effect of electron-withdrawing subs-
tituents on the rate of selenoxide decomposition, and this showed that
such groups increase both the rate and the yield of olefin produced.
A route to terminal olefins was developed but although the final step
was efficient, the initial alkylation step suffered due to the decreased
nucleophilicity of the selenium anion.
Et0H + CH3(CH2)11Br
2
Se(CH2)11CH3
NO2 THE
CH3(CH2)9CH==CH2
91%
The overall yield was 76%, compared with 59% obtained when diphenyl-
diselenide was used as a source of phenylselenolate anion.
The mildness of the selenoxide elimination process makes this an
attractive method for the introduction of unsaturation into complex molecules.
The synthesis of the important natural product vernolepin17 involved the
89%
OAc
NO2 OMe
H THE
02Me
DAC NN,/d//,, sON 50% H202
Me02C
18.
following transformation:
The final step in the synthesis18 of the naturally occurring lactone
(±) -diplodialide-A also utilised selenoxide fragmentation:
NaI04 o
0
SePh (±)-diplodialide-A
Nicolaou19
has developed a route to cyclic ethers which utilises
the high electrophilicity of selenenyl halides combined with the facile
fragmentation of selenoxides.
CO2Me
HO%s OR
SePh OH
HO'' OR
19.
OH
(1E)
PhSeC1 H202
CH2C12
THF 0-25o
"H,\ -78°
S ,......, .2
SePh +Se ...' * 0 ' \Ph
Raney Ni THF, 25°
I
This method has also been used20
to synthesise an analogue of
prostacyclin, (below)
CO2Me
1) H202 2) Li0H/Me0H
20.
A similar procedure21 was also developed for the preparation of
lactones.
CO2H
cl,) PhSeC1 -Et3N
CH2C12' -78° THF, 90%
H202 >
100% SePh
Raney Ni, THF,
25°, 85% . 25
030 2. Selenone Esters
Earlier work22
utilised the action of pyridine and hydrogen selenide
on the imidate ester hydrochloride to give moderate yields of selenonesters
e.g. methylselenonebenzoate (22)
OPh
(22)
Recently, 0-cholesterylselenonebenzoate (24) has been obtained23 in
good yield by treating the salt (23) with sodium hydrogen selenide, prepared
by the borohydride reduction of elemental selenium.
1 R....Thr, OR
N+ / \C1
(23)
,-- OR
ROH + Ri Cl
Nt - / \C1
21.
Se + NaBH4 Et0H --). (Et0)3B + 3H2 + NaHSe
NaHSe
(24) R1=Ph,R=cholesteryl (78%)
(25) R1=H,R=cholesteryl (44%)
The selenone formate (25) was prepared in lower yields and decomposed
rapidly in air.
Aryl or alkylethynylthiolates were known to react with alcohols under
certain conditions to give thionesters24. Recently in a similar reaction
it was found25 that in very dilute solutions the corresponding selenium
analogues (26) reacted with solvent alcohol to give selenoesters. In more
concentrated solutions, however, the diselenafulvene was formed. The
latter reaction was catalysed by traces of acid.
Se
R1OH II 1 R--CEEC--Se- K+ > R-- CH2-- C-- OR dilute
1
H+ (26) base
fe-
R---CH=C---OR1
R = PhCH2
R1= Me
The selenonesters were formed in only moderate yield and were not
mCPBA __Se --.) )== Sep 7
n 0' e-----,
0 + Se
(31)
22.
submitted for microanalysis. On treatment with base a bathochromic shift
was observed in the ultraviolet spectrum and this may be attributed to
enolisation, as shown above.
3. Selenoketones
In 1927, Lyons and Bradt26
claimed to have prepared monomeric aliphatic
selenoketones but their products were poorly characterised and the claim
was almost certainly unjustified. Barton et alr,28 heated a mixture of
the phosphoranylidene hydrazone (27) and selenium powder in the presence of
a trace of.butylamine and obtained the selone (28) as a blue liquid in 35%
yield. Use of the fenchylidene hydrazone derivative (29) gave the corres-
ponding selone (30) as blue crystals in 28% yield.
Se N—N=PPh3 + Se )).-=
trace iN.C."1H, --
120o 20h `). =
(27) (28)
(29)
(30)
These selones were thermally stable, being recovered after prolonged
heating at 150° under a nitrogen atmosphere. Oxidation with mCPBA at -80°
caused loss of the blue colour, but warming to room temperature gave only
the ketone and selenium. It was thought that the selenine (31) was formed
at low temperatures but that this species decomposes, possibly via the three-
membered cyclic transition state (32) on warming.
23.
Treatment of the selone (28) with tributylphosphine or sodium-
potassium alloy gave 2,2,4,4-tetramethylpentane.
)—Se
Bu3P
or Na/K
Reduction with ethanolic borohydride however, gave the diselenide
(33).
Se Se (33)
The addition of radicals to di-t-butyl selone (28) shows it to be an
extremely good radical trap29.
RnM + Se R
nMSeBut
2
(34) (28) (35)
RnM = CH3, CF3, Me3Sn, Me3C0
The radicals (34) add rapidly to the selone and the adducts (35) are
fairly persistent. The addition of Me3C0• is so fast that it competes with
its attack on good H-donors, such as trimethylsilane, even when the latter
are present in one hundred-fold excess.
4. Episelenides
Although episelenides have not been isolated, evidence for their exis-
tence continues to accumulate. Clive and Denyer30 published a general route
to olefins involving the reaction of triphenylphosphine selenide and
trifluoroacetic acid with epoxides. It was believed that an episelenide
was formed but that this underwent spontaneous breakdown to the olefin and
24.
elemental selenium.
AoPhn r- -
Ph3P=Se 0 Se Se
\ cF3co2
Pq Pe Fr Ri R' Fe 14 Ize
The reaction was rapid at room temperature and the conversion was
stereospecific. Thus trans-stilbene oxide gave trans-stilbene in 71%
yield. Chan and Finkenbine31 reported the same reaction and they claimed
that n.m.r. studies further demonstrated the intermediacy of an episelenide.
The reaction mixture showed complete absence of epoxide at low temperature,
no selenium was precipitated and a new signal at 3.66 was observed. On
warming to room temperature, this signal vanished, selenium was precipitated
and the olefin was formed.
Olefins can also be obtained32 by treating epoxides with selenocyanate
ion in neutral or slightly alkaline conditions. An intermediate episelenide
was again implicated.
Fe
t Se
25,
In this way, trans-stilbene and cyclohexene were formed quantita-
tively from their epoxides, but the cyclooctene and cyclopentene systems
failed to react, probably because steric factors prevented the seleno-
cyanate nucleophile from attacking from the rear of the epoxide-ring.
Since epoxides are readily opened under acidic conditions, the selectivity
of this procedure affords a potential method for the protection of double
bonds which are in different environments.
Perhaps the most striking example of the use of episelenides in
olefin synthesis was provided by Barton et al.27,28 who synthesised hexa-
methy1-2,21-binorbornylidene (36), the most highly hindered olefin yet
prepared, by the reaction of the selone (30) with the phosphoranylidene
hydrazone (29). The mechanism involves nitrogen and selenium extrusion
from the isolable 1,3,4-selenadiazoline (37), and an episelenide is thought
to be an intermediate.
( Se N-N=PPh3
(30) (29) (37)
q'A (36), 24%
26.
A recent conversion33 of either epoxides or episulphides to olefins
utilises the novel reagent 3-methyl-2-selenooxobenzothiazole (38). Once
again the reaction is stereospecific and is thought to proceed via the
episelenide.
Me
N
S
Y = 0 or S
+ Se
In this way, trans-stilbene oxide afforded trans-stilbene in 97% yield.
27.
THE SYNTHESIS OF 0-QUINONES
As the synthesis of quinones was the subject of an extensive review34
in 1974, this section will summarise only those methods which are specific
for the preparation of o-quinones from non-quinoid precursors and will also
include a survey of the more recent literature.
Most of the known syntheses of ortho-quinones involve oxidative
procedures, the typical precursors being phenols, phenolic ethers or, in
some cases, hydrocarbons. However, by far the most general route to
o-quinones involves oxidation of catechols by a variety of oxidants. The
oxidation of monohydric phenols by either one- or two-electron oxidants is
also a common process although this generally shows a marked preference for
2:quinone formation.
The use of hydrocarbons as substrates is limited owing to the general
severity of the reaction conditions.
1. Oxidation of Catechols
Treatment of catechols with fresh silver oxide in dry ether or benzene
in the presence of anhydrous sodium sulphate35 gives the o-quinones in high
yield. A recent improvement36 of this reaction uses silver carbonate and
celite as the mild oxidant.
OH Ag20 or
OH Ag2CO3/Celite
28.
The rather unstable o-benzoquinone can also be prepared37
(86% yield)
by the reaction of a chloroform solution of catechol with ceric sulphate in
aqueous sulphuric acid.
Oxidation of catechols38 with tetrachloro- or tetrabromo-o-benzoqui-
none gives o-quinones provided that the redox potential of the catechol
is lower than that of the oxidant.
pcOH
OH
OH
OH
X = CI or Br o.-Quinones prepared in this way include (39)39, (40)
40, and (41)38.
However, the method fails with alizarin and related compounds.
(39), 84% (40), 94%
0 (41), 85%
(42)
29.
High potential quinones of type (42) are usually made by oxidising
alizarin, etc. with lead tetraacetate41.
Many other oxidants are suitable for o-quinone preparation including
dichlorodicyanoquinone42 i , iodate43, potassium ferricyanide
44 and periodate
45.
2. Oxidation of Catechol Ethers
. Treatment of monoethers of catechols with sodium periodate
45 in either
water or aqueous acetic acid gives o-quinones in good yield. The reaction
is regarded as a nucleophilic attack by water on a periodate ester to give a
hemi-ketal which subsequently yields the quinone.
H2O:
OMeID e OMe OMe
OH 0 0 17 -I 030 H
Oxidation of catechol dimethyl ethers is of little synthetic importance
unless there are substituents at positions 4 and 5, when treatment" with
silver oxide in cold aqueous dioxan acidified with nitric acid affords
o-quinones in moderate yields.
3. Fremy's Salt
The oxidation of monohydric phenols to quinones using Fremy's salt
(potassium nitrosodisulphonate (43)) proceeds rapidly and efficiently under
very mild conditions. In general, however, the major product is the p-quinone
and o-quinones are only formed in special cases. The mechanism for the
30.
formation of o-quinones (p-similar) is shown below.
OH
+ (K03S)2N0'
(43)
+ (K038)2NOH
(43)
HN(S03K)2 +
(44)
If the 4-position is unblocked then the -quinone is the
exclusive product. This result may be due to the large steric
requirement of the intermediate dienone (44) in the case of o-quinone
formation. Certain a-naphthols give a mixture of o- and p-quinones
(5-hydroxy-1,2- and 1,4-naphthoquinone from 1,5-dihydroxynaphthalene47)
which may be ascribed to steric restriction of -dienone formation
by the peri-substituent.
If the para-position is occupied by alkyl (or alkoxy) groups,
simpler phenols are converted to o-quinones in 70-90% yield.48 More
complex phenols such as (45) can also be selectively oxidised49 and,
in general, substituents and side chains are not attacked by Fremy's
salt.
+ 500
5 h
Br
+
0 (46), 30%
0
HO
31.
(45)
75%
4. Other Reagents
Hydrocarbons provide a relatively unfavourable substrate for oxi-
dation to quinones and the method is limited in practice to those few
hydrocarbons which are readily available and form stable quinones.
Treatment50 of 1-bromonaphthalene with ceric ammonium sulphate in
a mixture of dilute sulphuric acid and acetonitrile gave a mixture con-
taining a 30% yield of the o-quinone (46). However, this method is of
limited application and, generally, p-quinones are formed wherever possible.
0 0
10%
18%
OH
02' Cu2+
64% R2N
+ 2R2NH
32.
Many other procedures afford o-quinones but they are not general.
Thus lead tetracetate oxidation of phenols51 gives varying yields of,
inter alia, o-quinones, and 3-methyl-l-tetralone has been oxidised
with selenium dioxide52
to a mixture of the o- and p-quinones.
When the oxidation of phenols by molecular oxygen is accomplished,
in the presence of cupric ions and a secondary amine such as morpholine,
amino-substituted o-quinones are rapidly produced.53
Thus 1- and 2-naph-
thol are converted to 4-morpholine-.1,2-naphthoquinone, whereas phenol affords
4,5-dimorpholino-1,2-benzoquinone.
OH
R2NH
0 Cu2+
37%
OH
+ R2NH
2+ 2' 84%
NR 2
R2N H = 0 NH
33.
In conclusion, therefore, it is apparent that the only good general
synthesis of o-'quinones is via oxidation of catechols. Monohydric phenols
give, wherever possible, the p-quinones, and oxidation of hydrocarbons
requires vigorous conditions and usually gives complex mixtures of
products.
REFERENCES
1. D.L. Klayman and W.H.H. GIInther, "Organic Selenium Compounds:
Their Chemistry and Biology", Wiley and Sons, New York, 1973.
2. idem, ibid, p. 207.
3. D.N. Jones, D. Mundy, and R.D. Whitehouse, J.C.S. Chem. COMM.,
1970, 86.
4. K.B. Sharpless, M.W. Young, and R.F. Lauer, Tetrahedron Letters,
1973, 1979.
5. D.L.J. Clive, J. C. S. Chem. Comm., 1973, 695.
6. K.B. Sharpless and R.F. Lauer, J. Amer. Chem. Soc.,1973, 95, 2697.
7. H.J. Reich, J. Org. Chem., 1974, 39, 428.
8. K.B. Sharpless and R.F. Lauer, J. Org. Chem., 1974, 39, 429.
9. K.B. Sharpless, R.F. Lauer, and A.Y. Teranishi, J. Amer. Chem. Soc.,
1973, 95, 6137.
10. H.J. Reich, I.L. Reich, and J.M. Renga, J. Amer. Chem. Soc.,
1973, 95, 5813.
11. H.J. Reich, J.M. Renga, and I.L. Reich, J. Org. Chem.,
1974, 39, 2133.
12. D. Gorenstein and F.H. Westheimer, J. Amer. Chem. Soc.,
1970, 92, 634.
13. P.A. Grieco and M. Miyashita, J. Org. Chem., 1974, 39, 120.
14. H.J. Reich and K. Shah, J. Amer. Chem. Soc., 1975, 97, 3250.
3'4.
35.
15. H.J. Reich, J.M. Renga, and I.L. Reich, J. Amer. Chem. Soc.,
1975, 97, 5434.
16. K.B. Sharpless and M.W. Young, J. Org. Chem., 1975, 40, 947.
17. P.A. Grieco, M. Nishizawa, S.D. Burke, and N. Marinovic,
J. Amer, Chem. Soc., 1976, 98, 1612.
18. T. Ishida and K. Wada, J.C.S. Chem. Comm., 1977, 337.
19. K.C. Nicolaou and Z. Lysenko, Tetrahedron Letters, 1977, 1257.
20. K.C. Nicolaou and W.E. Barnette, J.C.S. Chem. Comm., 1977, 331.
21. K.C. Nicolaou, and Z. Lysenko, J. Amer. Chem. Soc., 1977, 99, 3185.
22. R. Mayer, S. Scheithauer, and D. Kunz, Chem. Ber., 1966, 99, 1393.
23. D.H.R. Barton and S.W. McCombie, J.C.S. Perkin I, 1975, 1574.
24. R. Raap, Can. J. Chem., 1968, 46, 2251.
25. F. Malek-Yazdi and M. Yalpani, J. Org. Chem., 1976, 41, 729.
26. R.E. Lyons and W.E. Bradt, Ber., 1927, 60, 824.
27. T.G. Back, D.H.R. Barton, M.R. Britten-Kelly, and F.S. Guziec Jr.,
J.C.S. Chem. Comm., 1975, 539.
28. T.G. Back, D.H.R. Barton, M.R. Britten-Kelly, and F.S. Guziec Jr.,
J.C.S. Perkin I, 1976, 2079.
29. J.C. Scaiano and K.U. Ingold, J.C.S. Chem. Comm., 1976, 205.
30. D.L.J, Clive and C.V. Denyer, J.C.S. Chem. Comm., 1973, 253.
31. T.H. Chan and J.R. Finkenbine, Tetrahedron Letters, 1974, 2091.
36.
32. J.M. Behan, R.A.W. Johnstone, and M.J. Wright, J.C.S. Perkin I,
1975, 1216.
33. V. Calo, L. Lopez, A. Mincuzzi, and G. Pesce, Synthesis,
1976, 200.
34. S. Patai, (Ed.), "The Chemistry of the Quinoid Compounds",
Wiley and Sons, 1974.
35. J. Cason, Org. Reactions, 1948, 4, 305.
36. V. Balogh, M. Fetizon, and M, Golfier, J. Org. Chem.,
1971, 36, 1339.
37. R. Brockhaus, Ann., 1968, 712, 214.
38. L. Horner and W. DUrckheimer, Z. Naturforsch., 1959,24b, 741.
39. L. Horner, W. DUrckheimer, K-H, Weber, and K. Dolling,
Chem. Ber,, 1964, 97, 312.
40. L. Horner and K-H. Weber, Chem. Ber., 1967, 100, 2842.
41. M.V. Gorelik, Zh. Org. Aim., 1968, 4, 513.
42. P. Boldt, Chem. Ber., 1966, 99, 2322.
43. L. Horner and K-H. Weber, Chem. Ber., 1965, 98, 1246.
44. Review; H, Musso, Angew.Chem., 1963, 75, 965;
Angew. Chem. Internat. Edn., 1963, 2, 723.
45. E. Alder and R. Magnusson, Acta. Chem. Scand., 1959, 13, 505.
46. C.D. Snyder and H. Rapoport, J. Amer. Chem. Soc., 1972, 94, 227.
47. H,J, Teuber and N. Getz, Chem. Ber., 1954, 87, 1236.
37.
48. F.R. Hewgill and B.S. Middleton, J. Chem. Soc., 1965, 2914.
49. H.J. Teuber, Chem. Ber., 1953, 86, 1495.
50. M. Periasamy and M. Bhatt, Synthesis,1977, 330.
51. F. Wessely and J. Kottan, Monatsh., 1953, 84, 291.
52. F. Weygand and K. Schr8der, Ber., 1941, 74, 1844.
53. W. Brackmann and E. Havinga,Rec. Tray. Chim.,
1955, 74, 1937, 1021, 1070, 1100, and 1107.
38.
BENZENESELENINIC ANHYDRIDE: PREVIOUS WORK
Benzeneseleninic anhydride (1) has recently been shown1'2 to be a
versatile reagent for the oxidation of organic substrates. In this section
some of the properties and reactions of this compound are described and
other related work performed in these laboratories is discussed.
1. Synthesis
Benzeneseleninic anhydride has been known since 19093 but an efficient
synthesis was not devised until 19624, when it was found that ozonolysis
of diphenyldiselenide gave the anhydride quantitatively. It was postulated
that three intermediates were involved:
0 0 I 0 0 02 H
PhSeSePh---- -> PhSeSePhc-----> PhSe0SePh4,----PhSeSePh --PhSe-O-SePh
(1)
However, these intermediates could not be prepared when the calculated
amounts of ozone were used and, to date, they are still unisolable, despite
current interest5 in their properties.
The large scale preparation of benzeneseleninic anhydride is most
conveniently achieved by the nitric acid oxidation of diphenyldiselenide.
The resulting seleninic acid hydronitrate6 (2) may be converted quantitative-
ly to the anhydride by heating at 130° in vacuo for several hours.
0 0 0 HNO3 II A U II PhSeSePh --------*PhSe0H.HNO -------4 PhSeOSePh 3 vac
(2)
2. Properties and Reactions
Benzeneseleninic anhydride has a molecular weight of 360.12.
39.
No molecular ion is apparent in the mass spectrum, and peaks are recorded
at 314(38.7), 234 (37.1), 174 (42.0), 157 (85.5), 154 (75.8), 93 (27.4),
77 (100) and 65 (22.5).
This fragmentation pattern is similar to the aromatic solenoxide
fragmentation investigated by Rebane7, and the following scheme may be
proposed,
[phseor [Phol+
[PhSe0SePh
m/e 174 m/e 93 m/e 65
Ephse] + [ph]
m/e 157 m/e 77
[PhSePhil [Ph-Phj÷
[PhSeSePhi +
m/e 314
m/e 234 m/e 154
The selenium atom gives a characteristic group of peaks in the mass
spectrum which results from the typical distribution of the six major
natural isotopes': 74Se (0.87%), 76Se (9.02%), 77Se (7.58%), 78Se
(23.52%), 80Se ( 49.82%), and 82Se (9.19%). The peak arising from the
most abundant 80Se isotope is generally chosen to represent a selenium-
containing fragment.
Use of infra-red and nuclear magnetic resonance spectroscopy has
helped to confirm that, in contrast to the sulphur analogue, benzenesele-
ninic anhydride is a true anhydride with the symmetrical structure (1)
shown above, The so-called sulphinic anhydrides are actually sulphinyl
sulphones9 (3).
40.
0 0 II II
R--S--S--R (3) 11 0
Analysis of the vibrational spectrum was particularly useful in
demonstrating the presence of the Se-O-Se bridge within the molecule.
The data obtained by Paetzold10
et al. are summarized below.
Benzeneseleninic anhydride
Wave Numbers (cm-1)
vas
vs
PhSe
SeOSe
SeOSe
687 vs
590 vs
557 m
= valency vibrations
vs = very strong,
m = medium
The equivalence of the two phenyl groups was shown by nuclear magnetic
resonance spectroscopy11. Thus the
1H spectrum showed only two signals,
T1 2.167 (2H, ortho) and 2.350 (2H, meta and 1H, para), while the 13C
spectrum showed only four signals due to Cl, C2 and C6, C3 and C5, and C4.
0 0 II II
Ph Se 0 Se
Benzeneseleninic anhydride is a white powder melting at 164°, It is
hydrolysed by moist air giving benzeneseleninic acid but this process is
slow and no special precautions are needed when handling the reagent.
0 0 H
PhSeOSePh H2O
0
2PhSe0H
41.
The anhydride may be recovered unchanged after prolonged heating at
1600, although some sublimation occurs. It is unaffected by solvents such
as benzene, tetrahydrofuran and carbon tetrachloride at room temperature
but reacts rapidly with ethanol to give the ester (4) and benzeneseleninic
acid.
0 0 0 0 II II II iI
PhSeOSePh + EtOH PhSeOEt + PhSeOH
(4)
The reagent is only slightly soluble in tetrahydrofuran, dimethyl-
formamide and dimethylacetamide and does not dissolve in benzene, dichloro-
methane and diethyl ether. Consequently, the anhydride is most commonly
used as a suspension, and vigorous stirring during the reaction is
required.
During the course of studies on the synthesis of tetracycline carried
out in this department, it became necessary to introduce a hydroxyl group
into the 12a position of the derivative (5):
OH OH
OH
COR
OH
COR
HO 0 0 0 OH HO 0 0___/ 0
(5)
(6) R=OMe or NH
2
OH (11) (10)
OH
(7)
OH
OH +
0
(8) (12)
0 (14)
(9)
OH (13)
(15)
(16)
OH
42.
As standard methods, such as treatment with periodate12
,failed,
a new hydroxylation procedure was required.
Rosenfeld13 examined the effect of benzeneseleninic anhydride on the
simple phenols (7)-(9). Treatment of a solution of the phenols in dichlo-
romethane with excess benzeneseleninic anhydride gave mixtures of ortho-
and para-hydroxylated products. Thus 2,4-xylenol (7) gave the dimer of
the o-hydroxydienone (10) in 40% yield and the p-hydroxydienone (11) in
15% yield. Similarly, mesitol (8) gave the o-hydroxydienone dimer (12),
(48%) and the E:hydroxydienone (13), (30%). 2,6-xylenol (9) gave
2,6-dimethylbenzoquinone (14), (25%), 3,3',5,5'-tetramethylbiphenoquinone
(15) (40%) and a trace of the o-hydroxydienone dimer (16).
OH A OH OH
COR HO
COR COR OH 0
43.
However, when the phenols were first converted to the phenolate
anions (using sodium hydride), hydroxylation occurred specifically in the
ortho-position and only traces of a-isomer could be detected. Thus,
2,4-xylenol, (7) gave compound (10) in 45% yield, mesitol (8) gave compound
(12), (55%) and 2,6-xylenol (9), gave compound (16) in 44% yield.
Reaction of benzeneseleninic anhydride with the monoanions of the
tetracycline ring-A model compounds (17) gave the o-hydroxydienones (18)
in high yield.
R=NH2 (68%) (17) (18)
R=OMe (75%) (19)
The hydroxylated products (18) were sufficiently acidic to be
extracted into aqueous sodium bicarbonate solution, and subsequent acidi-
fication afforded the hydroxydienones, free from the quinones (19) and
other impurities. However, treatment of the tetracyclic derivative (5)
failed to yield the desired product (6) and a complex mixture of
products was obtained.
Hydroxylation of phenolate anions appeared therefore to exhibit much
greater ortho-selectivity than did the reaction with free phenols. In
the hope that increased yields of o-hydroxylated products might result,
the effect of generating the anions using a different base was examined.
When 2,4-xylenol (7) was treated first with sodium hexamethyldisilazide
and subsequently with benzeneseleninic anhydride a dark red compound was
rapidly produced. This material was isolated by chromatography and shown
to be the phenylselenoiminoquinone ((20), selenoimine).
OH
0 Na
44.
NaN(SiMe3)2
N SePh
(7) (20)
The first examples of this class of compound, (21) and (22), were
recently prepared14'15 by the reaction of selenenyl and seleninyl halides
with 1,1-di-ptolylmethenimine in the presence of triethylamine.
O C=--N H + PhSe(0)C1 2
C=N-Se(0)„Ph 2
(21) n=0
(22) n=1
The selenoimines obtained by Rosenfeld show similar spectral features
to the sulphur analogues (23) which result from the reaction of triben-
zenesulphenamide with phenols16.
OH
+ (Ph S)3N N SPh
(23)
Benzeneseleninic anhydride has also been used for the oxidation of
primary amines to carbonyl compounds17. Thus 2-adamantylamine was con-
verted quantitatively to adamant-2-one and 1-phenylbenzylamine gave
benzophenone in 97% yield.
1\1-N H
NH2
0
45.
100%
Ph Ph ›.-NH2 XO
Ph Ph
97%
When the procedure was applied to amines which could form enamines
however, only unrecognisable products were isolated.
Treatment of ketone hydrazones, oximes and semicarbazones with
benzeneseleninic anhydride affords the parent carbonyl compounds in good
yield.18 Some examples are shown below. Significantly, cholesta-1,4-
dienone was smoothly regenerated from the 27nitrophenylhydrazone derivative,
a transformation which could not be achieved using standard reagents.
Ph Derivative
Ph .11/ 0
Phenyl Hydrazone 90 57
Oxime 89 96
Semicarbazone 89 85
86%
46.
The 1,3-dithiolane and 1,3-dithiane protecting groups may be removed
from aldehydes and ketones by treatment with benzeneseleninic anhydride
at room temperature19. In the case of the tetracyclic carbinol (24),
the carbonyl compound was formed in 78% yield; all the standard methods
tried failed to achieve this conversion.
OH
OH
Ph
(24)
In other examples, the method is comparable or exceeds the literature
procedures.
47.
REFERENCES
1. D.H.R. Barton, P.D. Magnus, and M.N. Rosenfeld, J.C.S. Chem. Comm.,
1975, 301.
2. D.H.R. Barton, P.D. Magnus,S.V. Ley, and M.N. Rosenfeld,
J.C.S. Perkin I, 1977, 567.
3. H.W. Doughty, Amer. Chem. J., 1909, 41, 326. (Chem. Abs.,
1909, 3, 1749.)
4. G. Ayrey, D. Barnard)and D.T. Woodbridge, J. Chem. Soc.,
1962, 2089.
5. H.J. Reich, J.M. Renga, and I.L. Reich, J. Amer. Chem. Soc.,
1975, 97, 5434.
6. M. Stoecker and K. Krafft, Ber., 1906, 39, 2197.
7. E. Rebane, Acta. Chem. Scand., 1970, 24, 717.
8. L.B. AgenUs, Acta. Chem. Scand., 1968, 22, 1763.
9. H. Bredereck, A. Wagner, H. Beck, and R.-J. Klein, Chem. Ber.,
1960, 93, 2736.
10. R. Paetzold, S. Borek, and E. Wolfram, Z. Anorg. Chem.,
1967, 353, 53. R. Paetzold, A. Chem., 1964, 321.
11. M.N. Rosenfeld, Ph.D. Thesis, London, 1976, 46.
12. E. Adler, L. Junghahn, U. Lindberg, B. Berggren, and G. Westin,
Acta. Chem, Scand,, 1960, 14, 1261.
13. M.N. Rosenfeld, Ph.D. Thesis, London, 1976, 48.
14. F.A. Davis and E.W. Kluger, J. Amer. Chem. Soc., 1976, 98, 302.
48.
15. C.O. Meese, W. Walter, and H. Schmidt, Tetrahedron Letters, 1976, 3133.
C.O. Meese, W. Walter, and H-W. Muller, Tetrahedron Letters, 1977, 19.
16. D.H.R. Barton, I.A. Blair, P.D. Magnus, and R.K. Norris,
J.C.S. Perkin I, 1973, 1031.
17. M.R. Czarny, J.C.S. Chem. Comm., 1976, 81.
idem, Syn. Comm., 1976, 6, 285.
18. D.H.R. Barton, D.J. Lester, and S.V. Ley, J.C.S. Chem. Comm.,
1977, 445.
19. D.H.R. Barton, N.J. Cussans, and S.V. Ley, J.C.S. Chem. Comm.,
in press.
NaH
0 Na
OH
(1)
OH
(2)
OH
49.
RESULTS AND DISCUSSION
1. Hydroxylation of Phenols with Benzeneseleninic Anhydride
Earlier results1 indicated that treatment of phenolate anions with
benzeneseleninic anhydride afforded ortho-hydroxydienones in high yield,
with only traces of the para-isomers detectable. Further study of these
reactions, however, has shown that, in some cases, the selectivity is less
general than was at first recognised.
Thus, treatment of 2,4-xylenol with sodium hydride in tetrahydrofuran
followed by addition of one equivalent of benzeneseleninic anhydride gave
the p:hydroxydienone (1) as the major product (31%), identified by comparison
with an authentic sample2. No o-hydroxydienone dimer (2) could be detected,
but at least three other products were formed in low yield, and 34% of the
starting material was recovered.
When the reaction was performed using three equivalents of the
anhydride only 21% of 2,4-xylenol was recovered and the major product was
again the para-'isomer (1), (34%), with no o-hydroxylation being observed.
50.
Increasing the reaction time from two to twelve hours did not significantly
affect the result, and the same product distribution was obtained when the
reaction was carried out in glyme or benzene.
Reaction of 2,4-xylenol, without prior formation of the phenolate,
with the anhydride gave the same products in similar yields. It therefore
appears that use of the phenolate az substrate was without advantage.
An authentic sample of the o-hydroxydienone dimer (2) was prepared
by the periodate oxidation of 2,4-xyleno13.
OH
OH
104-
(2)
This compound exhibited characteristic peaks in the n.m.r, spectrum
at T: 8.3 (3H, s), 8.6 (6H, s) and 8.7 (3H, s) which were clearly not
present in the spectra of the crude products from the reaction of 2,4-
xylenol with benzeneseleninic anhydride.
When the sodium salt of 2,6-xylenol was treated with one equivalent
of the anhydride in tetrahydrofuran, the o-hydroxydienone dimer (3) was
isolated as an oil in 15% yield. Although a crystalline sample could not
be obtained, the spectral data were in good agreement with those previously
reported4, Other products isolated included 2,6-dimethylbenzoquinone (5%)
and 3,3',5,5'-tetramethylbiphenoquinone (4), (8%); 50% of the starting
material was also recovered.
0 (4)
OH
(3 )
•-• 4- 0 Na
OH HO
(5) (6)
Ph2Se203
51.
Attempts to increase the yield of the hydroxylation product either
by using three equivalents of oxidant or by heating the reaction mixture
merely increased the amount of quinone formed. Once again, essentially
the same result was obtained using the free phenol as substrate.
Oxidation of the sodium salt of mesitol with three equivalents of the
anhydride in tetrahydrofuran gave predominantly the 2.-hydroxydienone (5),
(48%) together with 17% of recovered starting material. A further product
(17%) melting at 111-112°, which gave T: 0.2 (1H, s), 2.5 (2H, s) and 7.7
(6H, s) in the n.m.r. spectrum, appeared to be the aldehyde (6) (lit.5 m.p.
113.5 -1140 ). This conclusion was supported by mass spectral and infrared
spectroscopic data (141- = 150, vmax.
3600 (br) and 1702 cm-1).
- 0 Na OH
OH
(7)
52.
There is some precedent for this observation, since benzeneseleninic
anhydride also oxidises the side chain methyl group of the xylenes in
boiling chlorobenzene.6
CHO
When the monosodium salt of the tetracycline ring-A model ester (7)
was similarly treated with one equivalent of benzenseleninic anhydride the
o-hydroxydienone (8) was obtained in 42% yield after chromatography. The
major byproduct was the quinone (9), (25%). Rosenfeld7 claimed that
chromatography was unnecessary since the pure hydroxydienone could be
extracted with aqueous sodium bicarbonate solution; however, it was found
that appreciable amounts of quinone (9) and benzeneseleninic acid were
also extracted.
1)NaH OH 2)Fh2se2o3
CO2Me -71/` HO CO2Me
0
(8) (9)
OH
CO2Me
Use of one third of an equivalent of the anhydride reagent, reported7
to give complete reaction, gave only 20% of the hydroxydienone.
The most plausible mechanism for the reaction of the phenolate with
benzeneseleninic anhydride is shown below. Initial nucleophilic attack
by the phenolic oxygen at the selenium atom of the reagent is followed
by a sigmatropic shift and subsequent cleavage of the Se-0 bond by, for
C 02Me step 2/ 0 H
OH CO2Me
the quinone may arise as follows:
OH 0
(9)
OH
CO2Me
step 1
Ph (10) 0= Se5
\ -'41 0
OSePh OH
1) step 1 2) step 2'
CO2Me
OH
CO2Me
OH
Ph Se° OSePh
0
H OSePh 0
02Me
OH
CO 2 eM 0) PhSel-
Nu (8 )
53.
example, water or benzeneseleninate anion.
OH
C 0 Me 2 0
%1,‘, 0
Ph Ph Se-0 Se(0)Ph
If the anion is instead formed on the 3-hydroxyl substituent then
Although pathway (a) involves less steps there would be a strong
driving force for rearomatisation of intermediate (10) so path (b)
cannot be discounted.
The initial step in these proposed mechanisms would be
Ph2Se203 10
Reactivity
: 1
: 1 PhCOC1/py 15
OH
OH
54.
expected to be strongly influenced by the nature of the substituents
ortho- to the phenolate anion. When a mixture of mesitol and the more
hindered 2,6-di-t-butyl-4-methyl phenol was treated with one equivalent
of benzeneseleninic anhydride at room temperature in tetrahydrofuran,
recovery of unreacted starting material after twenty minutes ohowed that
50% of the mesitol had been consumed compared with 5% of the 2,6-di-t-
buty1-4-methylphenol. This result suggests that mesitol reacted approxi-
mately ten times faster than the more hindered phenol. By comparison,
treatment of the same mixture of phenols with benzoyl chloride and pyridine
followed by recovery of the unreacted starting materials. showed that mesitol
was consumed approximately fifteen times as fast as the 2,6-di-t-butyl-
4-methyl phenol.
The reaction between benzeneseleninic anhydride and 2,6-di-t-butyl-
4-methyl phenol at room temperature gave a red oil as major product (11%).
N.m.r. spectroscopy showed peaks at T: 3.40 (1H, br.s.), 3.85 (1H, br.s.),
7.86 (3H, s) and 8.74 (9H, s) which are in good agreement with the reported
data8 for the quinone (11), (lit.
8 T: 3.37, 3.82, 7.84, and 8.74).
However, the sample could not be purified for further characterisation.
No hydroxydienones could be isolated from the reaction mixture.
55.
Loss of a t-butyl group suggests that the reaction might proceed
via a radical mechanism.
Attempts to prepare o-hydroxydienones by the reaction of benzene-
seleninic anhydride with thymol (12) or carvacrol (13) failed. The reactions
Un were complex, giving a number ofkidentifiable products.
OH
OH
(12)
(13)
2. Conversion of Phenols to Quinones
Consideration of the proposed mechanism for formation of the quinone
(9) from the tetracycline ring A model ester (7) suggested that treatment
of unblocked phenols with excess benzeneseleninic anhydride might provide
a general route to o-quinones, given suitable conditions.
When -naphthol was treated with three equivalents of the anhydride
at room temperature a slow reaction took place to yield o-naphthoquinone
(35%) and 1-phenylseleno-2-naphthol (14), (23%).
0 c0-5e-Ph
PhSe 0') OrSe Ph 0 0 0
+ Pi-de OSePh
(16) (15)
0 fr Ph Se0 SePh
,rb H
56.
(14)
On stirring the selenated naphthol (14) with the anhydride at
room temperature no reaction was observed. However, on warming the
mixture to 50° the quinone was formed in 85% yield. Accordingly when
oxidation of the naphthol was carried out at 50° no byproduct (14) was
observed and the quinone was formed in 63% yield.
The phenylseleno-naphthol (14) is probably formed by reaction of
the free phenol with an electrophilic phenylselenating agent. It is
possible that the seleninyl-selenenate (15), formed by attack of benzene-
seleninate anion on intermediate (16), or others, is capable of being the
selenating species.
(14 )
57.
Alternatively the free naphthol may be phenylselenated directly
by reaction with species such as intermediate (16).
It has been suggested that compound (15) may be an intermediate formed
during the ozonolysis of diphenyldiselenide9, but to date it has not been
isolated. Evidence for the existence of compound (15) has been obtained
by the reaction of the lithium salt of benzeneseleninic acid with benzene-
selenenyl chloride in tetrahydrofuran at 0°. The orange colour of the halide
disappeared to leave a pale yellow solution. No major product could be
isolated but treatment of the reaction mixture with 0-naphthol gave the
1-phenylseleno-derivative in 62% yield.
0 ti - 1 0-naphthol
PhSe02 Li + PhSeC1 [PhSe0SePhj
(15) (14)
Also, treatment of diphenyldiselenide with two equivalents of m-
chloroperbenzoic acid (mCPBA) gave a similar pale yellow solution which
gave compound (14) in 32% yield, on treatment with a-naphthol.
SePh 0 OH
PhSeSePh 222EL, [ PhSe0SePh) 0-naphthol
(15)
(14)
However, the possibility that the same transformation could be achieved by
an intermediate such as
0 II
PhSeSePh
0 cannot be discounted.
58.
Isolation of the ~-naphthoquinone from the reaction mixtures involved
initial dilution with chloroform followed by rapid washing with aqueous
sodium bicarbonate solution to remove benzeneseleninic acid. Finally,
passage through a short silica gel column removed diphenyldiselenide
(eluting with petrol) and the quinone was eluted with chloroform/petrol.
10 In this manner, several phenols were converted to ~-quinones in
good yield.
Phenol
rQCr0H
OH
OH (12)
OH
Quinone
o
(17)
o
Yield (%)
63
62
59
60
68
(18)
OH ,H
-SePh
0 Ph SeCl
SePh OH 0 OSePh
OSePh
(18)
22%
OH
59.
As l,2-thymoquinone (17) was not previously reported in the litera-
ture it was fully characterised by spectroscopy and microanalytical data.
Mechanistic considerations suggested that a likely intermediate in
the conversion of phenols to quinones might be compound (18) which could
subsequently undergo nucleophilic attack by benzeneseleninate anion to
give quinone.
r-02SePh
It was hoped that in the absence of benzeneseleninate anion this
intermediate would be sufficiently stable to permit isolation. However,
the room temperature reaction of 2,4-di-t-butylphenol with benzeneseleninyl
chloride, where the only nucleophile present would be chloride ion, gave
none of the expected product (18). The quinone (22%) and unreacted starting
material (54%) were the only identifiable components of the reaction mixture.
60.
In an attempt to trap intermediate (18) the phenolate anion was
treated with benzeneseleninyl chloride at -78°, allowed to warm to room
temperature and mixed with excess benzene thiol, (a soft nucleophile), in
the hope that attack on selenium would occur to give catechol-type products.
0— 0
05e Ph 0 11
PhSeC1 RT
-78°
Ph OH sie
"0 S/111Ph
OH
(18)
However, no catechol could be isolated after hydrolytic work-up.
Attempts to trap intermediate (18) in a similar way using lithium cyanide
were also unsuccessful, possibly due to solubility problems.
Although quinone formation was known to be slow at room temperature
it was hoped that the reaction of 2,4-di-t-butylphenol with benzeneseleni-
nic anhydride at room temperature would afford compound (18). Reaction at
the other ortho-position was thought to be unlikely due to steric factors.
Unfortunately, the reaction gave a mixture of unidentifiable products and
intermediate (18) could not be detected.
When the reaction was carried out in the presence of either lithium
cyanide or benzenethiol no catechol-type products were formed at room
temperature, whilst at 50°, the quinone was formed as normal, the added
nucleophiles apparently having no effect.
OH
OH
OH
Ph2Se203 >
O Se Ph
(18)
OH SePh 0- SePh OH
(14) (18)
OH
61.
A further attempt to prepare intermediate (18) by the reaction of the
monoanion of 3,5-di-t-butylcatechol (formed using sodium hydride) with
benzeneselenenyl chloride gave 3,5-di-t-butyl-o-benzoquinone as the only
identifiable product (38%). This may have been formed by attack of the
unreacted phenolate anion on the intermediate (18) as shown.
Hr 1 - OAr
OH OH OH /-4 0
PhSeCl
(18)
To counter this possibility, the reaction was repeated using the
free catechol in the presence of excess pyridine. However, the quinone was
formed in even higher yield (78%) and no intermediate (18) could be detected.
It seemed likely that the proposed intermediate (18) could act as
a phenylselenating agent towards unreacted phenol. When 2,4-di--t-butyl-
phenol was stirred for two hours with one equivalent of benzeneseleninic
anhydride and the resulting solution treated with -naphthol, 1-phenylseleno-
2-naphthol (14) was isolated in 18% yield. No di-t-butylcatechol was detec-
ted however,
62.
When, instead of treating with 0-naphthol, the reaction mixture
was concentrated and reductively acetylated with zinc, acetic anhydride,
acetic acid and pyridine, no catechol diacetate (19) was obtained although
this would have been expected if intermediate (18) had been present.
OH
OAc OSePh OAc
Zn/HOAc Ac20/ py
(18) (19)
In conclusion, it appears that although quinone formation almost
certainly occurs via the proposed intermediate (18), this species is too
unstable to be isolated or trapped under the conditions employed.
The major advantage offered by this new method of oxidation is
the high degree of o--selectivity of quinone formation. In cases where
2.-quinone formation was possible, e.g. a-naphthol, only ca 10% was detec-
table and only traces of para-products were observed in the oxidations
of thymol (12) and carvacrol (13). No other methods are able to convert
phenols to o-quinones with this selectivity.
However, there are limitations; when the simple phenols (20)-(25)
were similarly treated with the anhydride, complex mixtures of products were
obtained and no o-quinones could be isolated.
OH OH OH OH
NO2
(20)
(21)
(22)
(23)
OH
OH
OH
63.
OH HO OH
PhSe
(24)
(25)
(26)
(27)
Presumably, the quinones are formed but further oxidation takes
place. Use of less anhydride or lower reaction temperatures failed to give
any o-quinones.
With 4-t-butylphenol (26), benzeneseleninic anhydride gave a mixture
of products from which the dark purple phenylselenated quinone (27)
could be isolated in 4% yield. The structure of this compound was eluci-
_ dated by Rosenreld7 . Another member of this class of quinone was compound
(28), formed when 3-naphthol was stirred with the anhydride for twenty four
hours, again in low yield.
OH Ph2Se,
SePh
(28)
The phenylselenoquinones appear to be produced after initial o-quinone
formation. Possible mechanisms for this reaction are summarised below.
64.
Path (A)
Ph Se—
SePh SePh
Path (B)
Path (A) involves Michael addition of phenylselenolate anion to the
quinone followed by oxidation and path (B) involves attack by the quinone
at an electrophilic Se atom. Since the presence of such electrophilic
species had already been indicated, path (B) therefore appeared more
likely. In an attempt to prepare the phenylselenoquinone (28) by this
type of process,• 1,2-naphthoquinone was treated with several phenyl-
selenating agents, as shown in the Table.
In all cases, the phenylselenating agent was present in five-fold
excess. Little useful information was gained from these results.
OJ 0 - Se Ph
(30) (29)
OH
65.
Quinone Selenating agent Yield of (28)
PhSeSePh, 24h, RT 0
0 Li02SePh + PhSeCl, 24h, RT 4%
(PhSe)2 + 2mCPBA, 24h, RT 0
Ph2Se203'
24h, RT 3%
3. Conversion of Catechols and Quinols to Quinones
Benzeneseleninic anhydride was also used to smoothly convert many
catechols to o-quinones and quinols to p-quinones. Thus, treatment of
3,5-di-t-butylcatechol with one equivalent of the anhydride at room
temperature in tetrahydrofuran gave the quinone (29) in 88% yield.
The mechanism probably involves attack by the phenolic oxygen at
the selenium atom of the oxidant to give intermediate (30), which breaks
down to give quinone as shown.
Although catechol gave a rapid reaction, no identifiable products
could be isolated, even at lower temperatures (0°).
Treatment of 2,6-dimethylhydroquinone with one equivalent of benzene-
seleninic anhydride at room temperature gave the p-quinone (31) in 88%
66.
yield. Hydroquinone and 1,4-dihydroxynaphthalene were also converted to
the £-quinones (32) and (33) in high yield.
Quinol Product Yield (%)
0
88
OH o (31)
OH 0
0 84
OH o (32)
OH o
92
o (33)
This new method of converting catechols and quinols to quinones is
11 very mild and compares favourably with other procedures .
4. Formation of Selenoimines
7 Rosenfeld had reported that reaction of benzeneseleninic anhydride
with 2,4-xylenol and either the sodium or lithium salt of hexamethyldi-
silazane gave the selenoimine (34) in 91% yield.
OH
67.
1) MN(SiMe3)2
2) Ph2Se203
N Se Ph
(34 )
M = Na or Li
This interesting discovery prompted further investigations. When
the experiment was repeated using sodium hexamethyldisilazide only a 38%
yield of the selenoimine (34) was obtained. However, use of hexamethyl-
disilazane instead of the salt gave the selenoimine in 61% yield, in an
equally rapid reaction.
The reaction conditions were varied to optimise the yield although
little improvement could be made. Thus at lower temperatures the reaction
was slower but the yield of selenoimine remained constant. Below -10°C no
reaction occurred. The reaction was equally fast in all solvents employed,
e.g. benzene, tetrahydrofuran and glyme. Different proportions of the
reagents were used and the results are summarised in the Table.
2,4-xylenol HN(SiMe3)2 Ph2Se203 Yield (34)
1 equivalent 1.1 equivalents 0.3 equivalents 23%
1 II 1.1 tt 1.0 II 61%
1 t, 1.1 11 2.0 it 64%
1 I, 2.1 II 1.0 I/ 64%
1 it 2.1 It 2.0 II 70%
It is clear that little advantage may be gained by use of excess
reagents. Neither performing the reaction under nitrogen nor passing
68.
oxygen through the reaction mixture affected the results. Also the
reaction gave a similar result when carried out with the strict exclusion
of laboratory light.
A number of other phenols ~-'lere converted to selenoirnines in compa-
rable yields12 (Table)
Phenol Selenoimine Yield (%)
OH o NSePh
64
(34)
OH
© 45
o
CrNsePh
I . ~
(35)
OH o 58
NSePh
(36)
NSePh
56
OH
(37)
The selenoimines were characterised spectroscopically and gave
satisfactory microanalytical data. These new compounds are dark red
/Ph Ph Se S
/
N.
69.
and show distinctive absorptions at Xmax.
250-275 and 460-490 nm in the
ultraviolet spectrum. The carbonyl group resonates at a surprisingly
low frequency in the infrared spectrum. Thus selenoimine (34) absorbs
at 1605 cm-1 and it appears likely that there is a significant
contribution from the cyclic selenoxazoline structure (38).
(38)
In accordance with this, X-ray crystallography13 showed that the
selenoimine group adopts a syn-conformation (39) with the Se...0
distance only 45% greater than that of a formal Se-0 bond. The data
are summarised overleaf.
(39)
(40)
This finding is in direct agreement with the analogous thioimine
case where the syn-conformation is again adopted.
It was hoped that the selenoimine might be induced to flip to
the anti-conformation by the action of heat. However, on cooling a
melt of selenoimine (34), the resulting crystals did not appear to have
X-RAY STRUCTURAL STUDY OF SELENOIMINE (34)
Bond Lengths (R)
Se...0 2.575
Se--N 1.805
Se--C 1.924
N=C 1.308
C==0 1.240
NHAc
OAc
NO2
OH
OH
71.
undergone any change in properties.
The selenoimines were further characterised by conversion to the
aromatic N,0-diacetates by reduction with zinc, acetic anhydride, acetic
acid and pyridine. As the diacltates of 2-aminothymol and 2-aminocarvacrol
were previously unreported in the literature, authentic samples were
prepared by nitration and subsequent acetylation.
OH OAc
NHAc
NSePh PhSH or
thioglycollic acid
OH NH2
OH OAc
HN(SiMe3)2
Ph2Se203 (35)
Zn/Ac20
AcOH/py
NSePh
72.
The ease with which selenoimines are reductively acetylated suggested
that it might be possible to convert them to aminophenols, thus achieving
a mild, two-step ortho-amination procedure for phenols. Treatment of
selenoimine (34) with five equivalents of benzenethiol in benzene gave
85% of the crude aminophenol, isolated by chromatography. These products
are unstable to air and decompose rapidly during work-up. Use of thio-
glycollic acid as reducing agent, a reagent easily removed from the reac-
tion mixture by washing with aqueous sodium bicarbonate solution, gave
the aminophenol in 40% yield. These reaction conditions were not
optimised.
(34)
Hydrogen sulphide did not react with selenoimine (34).
It is apparent that, as in the case of quinone formation, selenoimine
formation is extremely ortho-selective. When selenoimine (35) was
prepared from phenol, only 3% of the pTisomer (41) was isolated. This
was converted directly to the N,0-diacetate, mpt 148-1500 (lit.14 150-1510).
(41)
OH
0 OEt
0
(43)
NaN(SiMe3)2
Ph2Se203
(42)
73.
In all other cases, however, no ETselenoimines could be detected,
although many coloured compounds were formed in trace amounts.
Treatment of 2,6-xylenol with hexamethyldisilazane and benzene-
seleninic anhydride gave the p--selenoimine (42) in 48% yield.
OH
HN(SiMe3)2
Ph2Se203
Rosenfeld had been unable to obtain this selenoimine using the
sodium salt of hexamethyldisilazane7, but claimed that the product was
obtained in 85% yield by reaction of the cathylate (43) under the usual
conditions.
However, these results could not be reproduced and only a 28% yield
of selenoimine (42) could be obtained.
When the unblocked cathylate (44) was treated with hexamethyl-
disilazane and benzeneseleninic anhydride the selenoimine (45) was formed
in 45% yield,
HN(SiMe3)2 NSePh
Ph2Se203
OEt
(45)
NaN(SiMe3)2
NSiMe3 PhSeX
N Si Me3
(46)
NSePh
NSePh
74.
OH
The mildness of selenoimine formation is underlined by the fact
that the sensitive cathylate group remains unaffected during the reaction.
The mechanism of selenoimine formation is not clear. Since
benzeneseleninic anhydride is known-to convert phenols to o-quinones, it
appeared likely that this could be the first step. The reaction of quinones
with sodium hexamethyldisilazide to give the silylated iminoquinones (46)
is known15, and further reaction of these with an electrophilio phenyl-
selenating agent would presumably give the selenoimines.
However, several pieces of evidence suggest that this route is
not followed:
(1) The formation of selenoimines occurs rapidly at room temperature
whereas quinone formation is slower and often requires heating.
(2) Some simple substrates such as 2,4-xylenol and phenol, which
readily give selenoimines, do not afford quinones when treated with
75.
benzeneseleninic anhydride alone. If quinones were intermediates in
selenoimine formation, then very rapid trapping must occur to prevent
the further oxidation that is usually observed, (see page 62).
(3) Treatment of o-quinones with hexamethyldisilazane and benzene-
seleninic anhydride does not always give selenoimines. Thus 1,2-thymo-
quinone gave a mixture of unidentifiable products. Selenoimine (36) could
not be detected.
X
HN(SiMe3)2
Ph2Se203 (36)
(4) Conversion of quinone intermediates to selenoimines should give
a mixture of two isomeric compounds since attack on the quinone could
occur at either of two sites.
N SePh N SePh 0
However, in the majority of cases only one selenoimine could be
isolated.
When a-naphthol was treated with hexamethyldisilazane and the
anhydride two selenoimines were isolated and characterisation as the
N,0-diacetates showed them to be isomers (47) and (48).
76.
OH
HN(SiMe3)2 N Se Ph
Ph2Se203
(47)
(48)
Rosenfeld7 had only observed isomer (47) in this reaction. The total
yield of selenoimine was 66% and the product ratio (47):(48) was 75:25.
Using 13-naphthol the same products were obtained in total yield of 61%.
Here the product ratio (47):(48) was 40:60. It appears likely that some
selenoimine is formed via the quinone in this particular case, possibly
due to the high stability and ease of formation of o-naphthoquinone, but
since a- and (3-naphthol do not give identical product ratios at least
one other pathway must be operative. Under the same conditions o-naphtho-
quinone gave isomers (47) and (48) in total yield of 45%, in the ratio
77:23 respectively.
HN(SiMe3)2
(47) + (48) Ph2Se203
The use of other reagents to effect conversion of phenols to
selenoimines has also been investigated.
Treatment of 2,4-xylenol with hexamethyldisilazane and one equiva-
lent of benzeneselenenyl chloride gave selenoimine (34) in 40% yield.
The reaction was rapid at room temperature. Use of benzeneseleninic acid
as oxidant gave a 25% yield of selenoimine.
The presence of trimethylsilyl leaving groups in the amine appears
77.
to be essential for efficient formation of selenoimines. When 2,4-xylenol
was treated with benzeneseleninic anhydride and excess liquid ammonia only
a trace of selenoimine (34) was detectable. No selenoimine was formed
using t-butylamine.
Tris-(trimethylsily1)-amine (49) was prepared by reaction of sodium
hexamethyldisilazine with trimethylsilyl chloride in the hope that this
compound would assist formation of selenoimines.
Me3SiCl + NaN(SiMe3)2 —411(SiMe3)3
(49)
However, treatment of 2,6-xylenol with the anhydride and one equiv-
alent of tris-(trimethylsily1)-amine gave the selenoimine (42) in only
19% yield, The lower reactivity of the tris-substituted amine may be
attributed to the steric hindrance about the nitrogen atom and the possible
difference in basicity caused by the introduction of a third trimethyl-
silyl group.
Reaction of 2,4-xylenol with benzeneselenenylchloride and tris-
(trimethylsilyl)-amine gave a mixture of unidentifiable products. No
selenoimine could be detected. These results are summarised below.
Phenol Oxidant Amine Product Yield(%)
2,4-xylenol
It
n
tt
2,6-xylenol
2,4-xylenol
PhSeC1
PhSe02H
Ph2Se203
IT
n
PhSeC1
HU (SiMe3)2 n
NH3 tBuNH2 N(SIMe3)3
I!
(34) n
n
NONE
(42)
(34)
40
25
trace
19
0
78.
Since selenoimine formation had been shown not to occur via a
quinone intermediate, and hexamethyldisilazane does not react with
phenols, it appeared possible that benzeneseleninic anhydride could
react with disilazane to give a species of type (50) which would then
react with phenols to give selenoimines.
0 II SePh
0 a/ ,SiMe3
Ph— SiMe3 )2 Ph-- Se -- N \
0 SiMe3
OSiMe3
Ph—Se= N— SiMe3 PhSe = N
(50)
However, treatment of benzeneseleninic anhydride with one equivalent
of hexamethyldisilazane in tetrahydrofuran gave no reaction after twelve
hours and the starting materials could be recovered quantitatively. When
the mixture was heated at 100° in a sealed tube, a small amount of diphenyl-
diselenide was obtained, but the starting materials were recovered in
greater than 95% yield.
Other attempts to prepare potential reactive intermediates were
also unsuccessful. Thus when tris-(trimethylsilyl)-amine was treated with
benzeneseleninic anhydride no reaction was observed after twelve hours.
Addition of benzeneselenenylchloride to either hexamethyldisilazane or
sodium hexamethyldisilazide gave intractable mixture of products from
which diphenyldiselenide could be isolated in yields of approximately
55%. Treatment of benzeneselenium trichloride with one equivalent of
tris-(trimethylsilyl)-amine gave no reaction and both starting materials
were recovered quantitatively.
79.
Reaction of benzeneseleninic anhydride with hexamethyldisilazane
might possibly be catalysed by the presence of the phenol. It was hoped
that a Lewis acid might exhibit a similar influence. However, when one
equivalent of boron trifluoride etherate was added to the anhydride, and
the mixture treated with hexamethyldisilazane no reaction occurred.
Benzeneseleninyl chloride (51onveniently prepared by ozonolysis of
a solution of benzeneselenenyl chloride in carbon tetrachloride16
, would
be expected to behave similarly to benzeneseleninic anhydride towards nucleo-
philes. Attention was therefore turned to this reagent.
PhSeC1
0 03 -0-PhSeC1 (51)
Treatment of 2,4-xylenol with one equivalent of benzeneselenenyl
chloride and hexamethyldisilazane gave selenoimine (34) in 18% yield.
OH 0 11
PhSeCl
HN(SiMe3)2
(34)
In an attempt to prepare the proposed reactive intermediate (50),
benzeneseleninyl chloride was treated at 0° under N2 with one equivalent
of lithium hexamethyldisilazide in THF. A white precipitate of lithium
chloride was formed but attempted work-up of the mixture either by
chromatography or crystallisation gave diphenyldiselenide (68%) as the
only identifiable product.
0 it
PhSeCl + LiN(SiMe3)2 -----s(PhSe)
2 + LiCl
OH 0 II
PhSeC1 LiN(SiNe3)2 +
(52)
so.
The same reaction was performed in the presence of 2,6-di--t-butyl-
phenol which, it was hoped, would be a good trap for PhSeN, but the major
product was the biphenoquinone (52), (24%).
The same product was obtained in 39% yield on treatment of 2,6-di-
t-butylphenol with hexamethyldisilazane and benzeneseleninic anhydride and
no selenoimine was observed. Formation of this type of product suggests
that a radical mechanism is operative.
When benzeneseleninyl chloride was treated with excess liquid
ammonia a white precipitate of ammonium chloride was rapidly produced. Fil-
tration and evaporation of unreacted ammonia gave a clear, pale yellow
solution which decomposed to a red oil on concentration. Attempts to
isolate a major component from the yellow solution by crystallisation failed.
When the clear yellow solution was treated with 2,4-xylenol the seleno-
imine (34) was formed in 4% yield. With 8-naphthol the solution gave
selenoimine (48) in 5% yield, free from positional isomer (47).
2,4-xylenol
NH3 ---* intermediate
Ph SeCI
0
z
\1-naphthole
(48), 5%
81.
This suggests that a small amount of a reactive intermediate may
be formed from ammonia and benzeneseleninyl chloride and that this gives
selenoimine (48) via a pathway which does not involve a quinone as
intermediate.
These results are summarised in the Table below.
Reaction Product
HN(SiMe3)2 + Ph2Se2' 100o no reaction observed
N(SiMe3)3 + Ph2Se203 RT II
HN(SiMe3)2 + PhSeC1 RT (PhSe)9 ca 55%
NaN(SiMe3)2 + PhSeC1 RT (PhSe)n ca 55%
N ( SiMe3)3 + PhSeC13 RT
L.
no reaction observed
HN(SiMe)+ PhSe0/BFRT II 32 2233 0
2,4-xylenol + HN(SiMe3)2 + PhSeC1 (34) 18%
-.0 -..-% LiN(SiMe)+ PhSe (PhSe)68% LiCl 32 N\ 2
Cl OH
LiN(SiMe3)2 + PhSe(0)C1 + (52), 2L%
HN(SIMe)3)2 + Ph2Se203 + 0 (52), 39%
NH3 + PhSe(0)C1 NH4C1
NH3 + PhSe(0)C1 + 2,4-xylenol (34), 4%
11 + 8-naphthol (48), 5%
5, Mechanism of Selenoimine Formation
The high degree of o-selectivity observed during selenoimine format-
ion suggests that the mechanism involves initial reaction of the phenolic
(a)
Ph (Se
0/ \\ f)(N-SiMe3
(a) ,
Ph (I
S%
0 0 NSePh SiMe3
Ph Se(0)-0X SePh
01 NSiMe3 OH ,SePh
H _A„ S iMe3 (b)
82.
oxygen with some species in the reaction mixture to give an intermediate
which is capable of delivering functionality into the ortho-position. A
sequence of this kind was postulated above to account for the region
specificity of quinone formation. Generation of the phenolate anion using
sodium hexamethyldisilazide would be expected to increase the rate of the
first step and thus improve the yield of selenoimine since undesirable side-
reactions would be disfavoured. However, this was not found to be the case.
It must therefore be concluded that the first step is fast compared with
subsequent steps and that increasing the electron-density on the phenolic
oxygen does not affect the overall reaction. The most probable mechanism
is shown below.
0 PhSel
,4 OX
.0H
( 5 3)
(Me3S0 NH Ph 2 t Se
t0H ,SePh
0' \`'l 1:Y \ 0— S Me3 SiMe3 (a) (a) ,
OSePh
,_N SePh SiMe3
NSePh
>
(54)
LO I-1 SePh
..7
H.N(SiMe3)2
83.
0 SePh
(18a)
This type of pathway is analogous to that postulated by Corey and
Schaefer7 to explain the behaviour of selenium dioxide towards ketones.
The intermediate (53) need not be formed; instead sequence (b) could
operate first to give intermediate (18a) which is then converted to seleno-
imine via sequence (a).
An alternative proposal is that the benzeneseleninic anhydride
reacts on carbon instead of oxygen as shown below:
o CSePh
t N-SiMe3 ■..A SiMe3
(55)
N SiMe3
Ph Se X
N Se Ph
84.
(Sharpless18 has suggested that intermediates of type (54) arc
involved in selenium dioxide oxidations). The regioselectivity is
explained by assuming a weak associative interaction between the
phenolic oxygen and the benzeneseleninic anhydride causing o-reaction
to predominate. The final step involves attack of an electrophilic
phenylselenating agent on the silylimine (55).
6. Redox Titration Study of Benzeneseleninic Anhydride Oxidations
The course of the reactions of benzeneseleninic anhydride with
phenols to give, under varying conditions, hydroxydienones, quinones
and selenoimines may be followed qualitatively by monitoring the disappear-
ance of phenol by t.l.c. However, a quantitative study of the relative
reaction rates of these three processes, which should provide valuable
mechanistic evidence, was complicated by several factors. Whilst
quinones (414 nm) and selenoimines (ca. 440 nm) have characteristic
absorptions in the ultraviolet spectrum, the principal absorption maxima
of the hydroxydienones (Amax:
225, 270, and 315 nm) are masked by other
components of the reaction mixture. A similar argument may be constructed
against the use of infrared spectroscopy, and an n.m.r. study would be
uninformative. Furthermore, since the benzeneseleninic anhydride is
used as a suspension, spectroscopic examination of the reaction mixture
would require considerable manipulation and significant errors could
result.
An attractive solution would be to observe the disappearance of
oxidant by a redox titration method. It seemed likely that iodide ion
should be oxidised by benzeneseleninic anhydride and other species which
were possibly present in the reaction mixture, according to the equations
below.
Iodide 21—
I2 + 2e
85.
Benzeneseleninic Ph2Se203
+ 611+
+ 6e r (PhSe)2 + 3H20
ie Ph2Se203 312
Benzeneseleninic 2PhSe02H + 6H+ + 6e -------4 (PhSe)2 + 4H2
0
ie PhSe02H ER 3/2 12
Benzeneselenenic 2PhSe0H + 2H+
+ 2e > (PhSe)2 + 2H20
ie PhSe0Ha---: 1/2 12
0
Reactive PhSeOSePh + 4H+ + 4e_
intermediate
(PhSe)2 + 2H20
ie PhSe02SePh 2 12
Thus, as the oxidation proceeds, the ability of the reaction mixture
to oxidise iodide ion to iodine should decrease and this would be
reflected in the titration results.
It was first necessary to show that benzeneseleninic anhydride would
liberate three equivalents of iodine. Early experiments were unable to
do this due to the low solubility of the anhydride, but when the reagent
was warmed in dilute sulphuric acid and excess acidic potassium iodide
solution was added, titration with N/10 aqueous sodium thiosulphate using
starch as indicator showed that 2.98 equivalents of iodine had been
liberated.
When the oxidising ability of a complete reaction mixture was to be
determined it was found advantageous to quench with sulphuric acid as
anhydride
acid
acid
86.
before but to subsequently extract the aqueous layer with ether to remove
diphenyldiselenide and other organic components. The resulting extract
would not oxidise iodide, and treatment of the aqueous phase with
potassium iodide and titration with sodium thiosulphate then gave the
oxidising ability of the reaction mixture. More consistent results were
obtained when the titration was performed in the presence of ethanol (ca.
20% by volume) as this helped to solubilise the liberated iodine. The
error due to aerial oxidation of the iodide was estimated to be ca 1%
and not significant. The oxidation of several phenols was studied and
in some cases the diphenyldiselenide produced was also recovered in order
to determine whether the loss in oxidising ability was equal to the per-
centage formation of diselenide. The titration data are shown in the
Table, and have been plotted as a function of time (graphs).
Titration Results
Reaction Time(min) Titre (ml) Oxidising Ability (%)
1. 2,4-xylenolate 0 14.9 99
+ Ph2Se203'
RT 5 12.7 85
20 11.5 78
120 10.2 68
2. 2,4-xylenolate 0 14.9 99
+ Ph2Se203' 0o
120 13.2 88
overnight 12.0 80
3. 2,4-xylenol 0 14.9 99
+ Ph2Se203' RT 5 13.8 92
120 13.2 88
120 8.6 58
87.
Titration Results/continued
Reaction Time(min) Titre(m1) Oxidising Ability (%)
. Mesitolate + 0 14.9 99 Ph2Se203' RT 20 13.1 88
60 12.5 83
120 12.3 82
5, 2,6-di-t-butyl- 0 14.9 99
4-methylphenolate 20 14.2 95
+ Ph2Se203' RT 60 12.6 84
120 12.2 81
6. 2,4-xylenol + 0 14.9 99
Ph2Se203 + 5 11.2 75
HN(SiMe3)2, RT 20 6.1 41
120 2.1 19
7. 2,4-xylenol 0 14.9 99
+ Ph2Se203 + 120 13.2 88
HN(SiMe3)2, 00 overnight 12.1 81
8. Cathylate (43) 0 14.9 99
+ Ph2Se203 + 120 8.1 54
HN(SiMe3)2' RT
. 2,4-di-t-butylphenol 0 14.9 99
+ Ph2Se203' RT 5 13.8 92
20 12.3 82
120 10.4 69
10, 2,4-di-t-butylphenol 0 13.5 90
+ Ph2Se203 5 6.9 46
A, 50° 20 6.8 45
120 4.8 32
88.
Diphenyldiselenide Recovery
Reaction Work-up Time(min) Yield
PhSeSePh (%)
la Acidic 0 0
5 10
20 12
120 13
lb Phosphate 0 0 Buffer
5 15
20 25
120 27
10 Normal 0 0
5 31
20 59
120 72
6 Normal 0 0
5 24
20 47
120 55
O\0
OXID
ISIN
G AB
ILIT
Y
100
90
0\0 80
OXID
ISIN
G A
BIL
ITY
70
60
50
40
30
20
10
89.
PLOTS OF TITRATION DATA OBTAINED FOR REACTIONS (1) - (10)
1. Hydroxylation conditions
100
50 .
0 10 20 30 60
120
TIME (mins)
2. Selenoimine and Quinone forming conditions
10 20 30 60 120
TIME (mins)
10 20 30 60
TIME (mins)
120
3. Diphenqldiselenide recovery
100
90
80 --, 0\° 70 .,
60 o w ri4 50
40
E 30 U 20
10
0
90.
91.
The reaction of 2,4-xylenolate anion with benzeneseleninic
anhydride at room te,Aperature appeared to be complete after about forty
minutes, by which time the oxidising ability of the reaction mixture had
dropped to 65%. When the reaction was performed at 0° the rate was very
slow and the oxidising ability had only dropped to 80% even after stirring
overnight. Reaction of the free phenol gave a similar titration curve
which showed a decrease in oxidising ability to 58%. From these results,
it appears that there is little advantage to be gained by using the
phenolate anion as far as reaction rates are concerned.
The reaction between mesitolate anion and benzeneseleninic anhydride
was slower (1 life: 9 min )than that of the less hindered xylenolate
(1 life; 6 min ) but similar to that of the anion of 2,6-di-t-buty1-4-
methyl phenol (1 life;10min). This suggests that the rate-limiting step
is not significantly affected by steric factors.
The rate of formation of the selenoimine from 2,4-xylenol appeared
to be slightly faster than hydroxylation (1 life: 5 min) and the oxidising
ability of the reaction mixture dropped to 19%. At 0° however, the
reaction was very slow and after fifteen hours the oxidising ability had
only decreased to 81%. The monocathylate of 2,6-dimethylhydroquinone was
treated with benzeneseleninic anhydride and hexamethyldisilazane and
after two hours the oxidising ability had decreased to 54%. This is a
higher value than for normal selenoimine formation because the phenol is
already in a higher oxidation level. The products were a mixture of
selenoimine and quinone.
Ortho-quinone formation appears to be slower than either hydroxylation
or selenoimine formation. Thus the reaction of 2,4-di-t-butylphenol with
benzeneseleninic anhydride in refluxing tetrahydrofuran gave t1 = 6 min -f
and the oxidising ability fell to 31%. At room temperature, however,
r.
OH
92.
the oxidising ability only decreased to 69% after two hours, although
the reaction appeared to have stopped. Only a trace of quinone was found
and this seems good evidence for the formation of intermediate of type
(18) (or its equivalent) as previously discussed.
OH OSePh
(18)
When the diphenyldiselenide was recovered from reactions where
either quinones or selenoimine was formed the yield was complementary to
the oxidising ability of the solution. Thus, for example, in run (6)
when the oxidising ability had decreased to 19% the yield of diphenyl-
diselenide was 72%. However, in the hydroxylation case this result could
not be obtained using an acidic work-up procedure, and the yield of dise-
lenide was low. When the reaction mixture was quenched with potassium
dihydrogenphosphate buffer solution however, the expected amount of
diselenide was recovered.
It seems likely that in the first two cases the diphenyldiselenide
comes from disproportionation of benzeneselenenic acid, which is formed
during the reactions.
3PhSe0H (PhSe)2 + PhSe02H + H2O
In the hydroxylation reaction, it is possible that the selenenic
acid is not formed and that some acid-stable, base-sensitive compound is
formed. This does not then give the diselenide on acidic work-up. Inter-
mediate (15) could be such a compound.
93.
0
PhSeOSePh (15)
However, when the pale yellow solution, prepared by treatment of benzene-
selenenyl chloride with the lithium salt of benzeneseleninic acid in
tetrahydrofuran, which is thought to contain (15) was treated with either
acid or buffer solution the diselenide was recovered quantitatively.
7. Oxidation of Benzylic Alcohols with Benzeneseleninic Anhydride
In view of the interesting results obtained from the reaction of
benzeneseleninic anhydride with phenols, a study of the reactions of alipha-
tic alcohols was undertaken.
Several benzylic alcohols were smoothly converted into ketones
in high yield. The results are tabulated below.
Alcohol Equivalents of anhydride
Product Yield
OH Ph I Ph 1 Ph2 C=0 85%
0 OH Ph H I Ph 1 PhCOCOPh 92%
OH OH Ph 1 1 Ph 2
le 770
However, the reaction between benzilic acid and the anhydride gave
only 5% of the ketone, even after heating in toluene for twenty four hours.
Previously23 it had been reported that this reaction gave benzophenone
in 65% yield at room temperature.
HO CO2H
Ph Ph Ph2Se2
03 Ph Ph
94.
5%
The mechanism of the oxidation of benzylic alcohols is probably
as follows:
0 Ph Se -(i0 Se(0)Ph 01 iii
O H O'Se Ph
Ph,,,L, ______,
Ph Ph ' Ph H
Ph
In contrast, cinnamyl alcohol did not react with the anhydride after
stirring for twenty four hours in tetrahydrofuran, although cinnamaldehyde
is formed at higher temperatures6
PhA/\ 0 H Ph2Se2
03
RT > Ph o
95.
EXPERIMENTAL
Melting points were determined on a Kofler hot stage and are
uncorrected. Infra-red spectra were recorded on a Unicam SP 200 or
Perkin Elmer 257 spectrophotometer. Ultra-violet spectra were recorded
in ethanol, unless otherwise stated, on a Unicam SP 800 spectrophotometer.
N,m,r, spectra were recorded in acid-free deuterochloroform with tetra-
methylsilane as an internal reference on a Varian EM 360 instrument. Mass
spectra were recorded on an A.E.I.M.S. 9 spectrometer. Microanalyses were
carried out within the Department of Imperial College.
Thin-layer chromatography, both preparative and analytical, was
carried out using GF254 silica plates.
Solvents were purified and dried according to standard19
techniques.
Petrol refers to the fraction with b.p. 40-60°. Removal of solvents under
reduced pressure was carried out below 40°.
The following abbreviations are used:
THE : Tetrahydrofuran
mCPBA meta-Chloroperbenzoic acid
P.l.c.: Preparative layer chromatography.
The following abbreviations apply to n.m.r. data:
singlet
doublet
triplet
quartet
broad singlet
multiplet
d
t
bs
m
96.
Benzeneseleninic Anhydride
A stirred suspension of diphenyldiselenide (10g) in water (10 ml)
at 60° was treated cautiously with concentrated nitric acid (ca. 10 ml)
in 1 ml aliquots until evolution of the oxides of nitrogen had ceased.
After cooling at 4° overnight, the white crystals of the nitric acid complex
of benzeneseleninic acid m.p. 112° were isolated by filtration, washed
with water and dried in air.
The complex was heated in vacuo at 120° for 72 h to give the
anhydride (ca 90%) as a white powder m.p. 164° (lit.,9 165°).
Benzeneselenenyl Chloride
A stirred solution of diphenyldiselenide (3.14 g, 10 mmol) in hexane
(25 ml) at 100 was treated with a solution of sulphuryl chloride (1.35 g,
10 mmol) in hexane (5 ml). After 30 min, the solvent was evaporated and
the orange solid was recrystallised from benzene to give benzeneselenenyl
chloride (306 mg, 80%) as large orange crystals, m.p. 62-63° (lit.16 m.p.
62,-,64°).
Benzeneseleninyl Chloride
A solution of benzeneselenenyl chloride (190 mg, 1 mmol) in dry
dichloromethane (3 ml) was treated with ozone, passed through a calcium
sulphate drying tube at 0° until the colour had faded to a pale yellow.
Dry oxygen (15 min) followed by nitrogen (15 min) was passed through the
solution to remove excess ozone. The benzeneseleninyl chloride solution
16 was used without further purification .
97.
Oxidation of Sodium 2,4-Xylenolatc with Benzeneseleninic Anhydride
A stirred solution of 2,4-xylenol (61 mg, 0.5 mmol) in dry THF
(4 ml) was treated with sodium hydride (80% suspension in oil, 22 mg,
1.5 equiv.) and to the resulting solution was added benzeneseleninic
anhydride (180 mg, 0.5 mmol). After 2 h the reaction was quenched with
aqueous potassium dihydrogenphosphate buffer solution (10%, 10 ml) and
extracted with chloroform (3 x 10 ml). The organic phase was dried
(anhydrous sodium sulphate) and concentrated and p.l.c. (on silica, using
ether/petrol, 1:1 as eluent) gave the p-hydroxydienone (1), (20 mg, 31%)
as an oil, T: 2,7-3.5 (2H, m), 3.95 (1H, d), 7.8 (1H, bs), 8.2 (3H, d),
and 8,7 (3H, s), m/e 138 (Mt).
2,4-Xylenol (21 mg, 34%) was also recovered.
Oxidation of 2,4-Xylenol with Benzeneseleninic Anhydride
The previous experiment was repeated without prior formation of the
xylenol sodium salt. The EThydroxydienone (1), (19 mg, 30%) was again
the only identifiable product.
Hydroxydienone Dimer (2)
Prepared by the sodium periodate oxidation of 2,4-xylenol according
to the method of Adler et al.3 in 19% yield (lit.3 20% yield) m.p. 236°
(lit.3 m.p. 237-238°).
Oxidation of Sodium 2,6-Xylenolate with Benzeneseleninic Anhydride
A stirred solution of 2,6-xylenol (61 mg, 0.5 mmol) in dry THF (4 ml)
was treated with sodium hydride (80% suspension in oil, 23 mg, 1.5 equiv.)
and to the resulting solution was added benzeneseleninic anhydride (180 mg,
98.
0,5 mmol). After 2 h the reaction was quenched with aqueous potassium
dihydrogenphosphate buffer solution (10%, 10 ml) and extracted with
chloroform (3 x 10 ml). The organic phase was dried (anhydrous sodium
sulphate) and concentrated. P.l.c. (on silica using ether/petrol, 1:1
as eluent) gave the o-hydroxydienone dimer (3) as an oil (9 mg, 15%),
T: 8.2 (3H, s), 8.7 (6H, bs), and 8.8 (3H, s), m/e 276 (M+), 2,6-dimethyl-
henzoquinone,(3mg, 5%), m,p. 71° (lit.5 m.p. 71-72°) and 3,3,5,5-tetra-
methylbiphenoquinone (5 mg, 8%), m.p. 210-213° (lit.27 m.p. 212-215°).
2,6-Xylenol (30 mg, 50%) was also recovered.
Oxidation of Sodium Mesitolate with Benzeneseleninic Anhydride
A stirred solution of mesitol (68 mg, 0.5 mmol) in dry THE (4 ml)
was treated with sodium hydride (80% suspension in oil, 20 mg, 1.25 equiv.).
To the resulting solution was added benzeneseleninic anhydride (180 mg,
0,5 mmol). After 2.5 h, the reaction was quenched with aqueous potassium
dihydrogenphosphate buffer solution (10%, 10 ml) and extracted with
chloroform (3 x 10 ml). The organic phase was dried (anhydrous sodium
sulphate) and concentrated. P.l.c. (on silica, using ether/petrol, 1:1
as eluent) gave the p-hydroxydienone (5), (36 mg, 48%) m.p. 121-123°
(lit.2° m.p. 123-4°), T: 3.35 (2H, s), 7.70-8.10 (1H, bs), 8.10 (6H, s),
and 8.55 (3H, s), m/e 152 (Mt).
A further product was obtained, believed to be 3,5-dimethy1-4-
hydroxybenzaldehyde (26 mg, 17%) m.p. 111-112° (lit.5 m.p. 113.5-114°),
vmax, (Nujol): 3600 (br) and 1702 cm.-1, T: 0.2 (1H, s), 2.5 (2H, s),
and 7.7 (6H, s), m/e 150 (e).
99.
Oxidation of the Sodium Salt of Tetracycline Ring-A Model Ester (7) with
Benzeneseleninic Anhydride
A stirred solution of the ester (196 mg, 1 mmol) in THF (5 ml)
has treated with sodium hydride (80% suspension in oil, 30 mg, 1 equiv.)
to form the monoanion. After 10 min benzeneseleninic anhydride (360 mg,
1 mmol) was added and stirring was continued for 45 min. Literature7
work-up gave a mixture of three products which was chromatographed on
silica plates using ether/ethyl acetate mixtures as eluent to give
hydroxydienone (8), (100 mg, 47%) m.p. 109-110° (lit.7 m.p. 111°), quinone
(9), (44 mg, 21%), m.p. 66-67° (lit.7 m.p. 68°•) and benzeneseleninic acid
(17 mg, 9%) m,p. 122-3° (lit.22 m.p. 122-4°).
Repeating the experiment using only 0.33 equivalents (120 mg) of
the anhydride gave the hydroxydienone (8), (47 mg, 22%) in reduced yield.
Competitive Oxidation of Mesitol and 2,6-Di-t-Butyl-4-Methylphenol with
Benzeneseleninic Anhydride
A stirred solution of mesitol (68 mg, 0.5 mmol) and 2,6-di-t-buty1-
4r,methylphenol (110 mg, 0.5 mmol) in dry THF (7 ml) was treated with
benzeneseleninic anhydride (180 mg, 0.5 mmol). After 20 min, the reaction
mixture was filtered and p.l.c. (on silica, using petrol followed by ether/
petrol mixtures as eluent gave unreacted mesitol (34 mg, 50%) and 2,6-di-
t-buty1-4,methylphenol (104 mg, 95%).
Competitive Benzoylation of Mesitol and 2,6-Di-t-Butyl-4-Methylphenol
A stirred solution of mesitol (68 mg, 0.5 mmol) and 2,6-di-t-butyl-
4-methylphenol (110 mg, 0.5 mmol) in benzene (5 ml) was treated with benzoyl
chloride (70 mg, 0.5 mmol) and pyridine (2 ml). After 2 h the reaction
mixture was diluted with chloroform (20 ml), washed with dilute aqueous
100.
hydrochloric acid (3 x 10 ml) and water (20 ml) and the organic pha,;e
was dried (anhydrous sodium sulphate). Concentration and p.l.c. on silica,
using petrol followed by petrol/ether mixtures as eluent gave unreacted
mesitol (37 mg, 55%) and 2,6-di-t-butyl-4-methylphenol (106 mg, 97%).
Oxidation of 2,6-Di-t-Butyl-4-Methylphenol with Benzeneseleninic Anhydride
A stirred solution of 2,6-di-t-butyl-4-methylphenol (110 mg, 0.5
mmol) in dry THF (5 ml) was treated with benzeneseleninic anhydride
(180 mg, 0.5 mmol). After 2 h the reaction mixture was filtered and
concentrated. P.l.c. (on silica, using ether/petrol, 1:1 as eluent) gave
a red oil (12 mg, 11%) T: 3,40 (1H, bs ), 3.85 (1H, bs), 7.86 (3H, s),
and 8,74 (9H, s), m/e 178. The oil decomposed rapidly and further puri-
fication could not be effected.
Oxidation of Thymol with Benzeneseleninic Anhydride
A stirred solution of thymol (75 mg, 0.5 mmol) in THF (5 ml) was
treated with benzeneseleninic anhydride (180 mg, 0.5 mmol). After 2 h
the reaction mixture was filtered and concentrated. No identifiable
products could be isolated by chromatography. Thymol (30 mg, 40%) was
recovered.
Oxidation of Carvacrol with Benzeneseleninic Anhydride
The previous experiment was repeated using carvacrol instead of
thymol. A mixture of unidentified products was again obtained and carvacrol
(35 mg, 47%) was recovered.
Oxidation of 2-Naphthol with Benzeneseleninic Anhydride
A stirred solution of 2-naphthol (72 mg, 0.5 mmol) in dry THF (5 ml)
101.
was treated with benzeneseleninic anhydride (540 mg, 1.5 mmol) at room
temperature. After 3 h the reaction mixture was filtered and concentrated.
Chromatography (silica gel column, using chloroform/petrol mixtures as
eluents)gave (i) 1-phenylseleno-2-naphthol (14) as white crystals (42 mg,
28%), m.p, 76-78° (lit.5 m,p. 77-78°) and (ii) 1,2-naphthoquinone (28 mg,
35%), m,p. 144-146° (lit.5 m.p. 145-6°).
Oxidation of 1-Phenylseleno-2-Naphthol with Benzeneseleninic Anhydride
A solution of 1-phenylseleno-2-naphthol (150 mg, 0.5 mmol) in dry
THF (5 ml) was added to a stirred suspension of benzeneseleninic anhydride
(180 mg, 0.5 mmol) in THF (5 ml), maintained at 50°. An orange colour
was rapidly produced. After 30 min the reaction mixture was diluted with
chloroform (20 ml), washed with aqueous sodium bicarbonate solution (10%,
2 x 20 ml) and water (20 ml), dried (anhydrous sodium sulphate) and evapora-
ted to dryness in vacuo. Chromatography (silica gel column, using ether/
petrol 20% as eluent) gave 1,2-naphthoquinone as orange crystals (72 mg,
89%) m.p. 143-145° (lit.5 m.p. 145-6°).
Lithium Phenylseleninate
A solution of benzeneseleninic acid (190 mg, 1 mmol) in dry THF
(5 ml) was treated with butyl lithium (64 mg, 1 mmol) at room temperature.
After 10 min, the solvent was removed under reduced pressure and the residue
was washed with ether (3 x 5 ml) and dried in vacuo to give lithium
phenylseleninate (182 mg, 92%) as a white powder.
Diphenylseleninylselenenate (15)
A solution of benzeneselenenyl chloride (95 mg, 0.5 mmol) in dry THF
(5 ml) was added to a stirred suspension of lithium phenylseleninate (107 mg,
102.
0.5 mmol) in THF (3 ml) with careful exclusion of moisture. The initial
orange colour disappeared rapidly to give a pale yellow solution. After
filtration, the mixture was chromatographed (silica gel column, using petrol/
chloroform mixtures as eluents) to give diphenyldiselenide (94 mg, 60%)
and benzeneseleninic acid (19 mg, 20%) as the only identifiable products.
Attempts to crystallise the seleninylselenenate (15) from the pale yellow
solution were unsuccessful. Subsequent experiments with the reagent (15)
were therefore carried out using the yellow solution without further
purification.
Reaction of 2-Naphthol with Diphenylseleneninylselenenate (15)
A solution of 2-naphthol (72 mg, 0.5 mmol) in THF was added to a
solution of the seleninylselenenate reagent (15) (0.5 mmol) in THF (8 ml)
After 2 h chromatography (silica gel column, using ether/petrol, 5% as
eluent) gave 1-phenylseleno-2-naphthol (93 mg, 62%) m.p. 75-77° (lit.7
m.p. 770).
Oxidation of Diphenyldiselenide with m-Chloroperbenzoic Acid
A solution of diphenyldiselenide (157 mg, 0.5 mmol) in THF (10 ml)
was treated with m-chloroperbenzoic acid. (180 mg, 2 equivs.) to give a
pale yellow solution. Chromatography gave diphenyldiselenide as the only
identifiable product.
A solution of 2-naphthol (72 mg, 0.5 mmol) in THF (3 ml) was added
to the pale yellow solution and after 2 h, p.l.c. (on silica gel, using
ether /petrol, 5% as eluent) yielded 1-phenylseleno-2-naphthol (48 mg,
32%) m.p, 75-77° (lit.7 m.p. 77°),
103.
Preparation of Quinones from Phenols (General Method)
A solution of the phenol (0.5 mmol) in dry THF (5 ml) was added
dropwise over 15 min to a stirred suspension of benzeneseleninic anhydride
(180 mg, 0.5 mmol) in THF (10 ml) at 50°. The disappearance of starting
material was monitored by analytical t.l.c, Further oxidant was added
(ca, 0,1 equiv.) until no phenol remained. The reaction mixture was
dissolved in chloroform (25 ml) washed with aqueous sodium bicarbonate
solution (10%, 2 x 20 ml) and water (20 ml) and dried (anhydrous sodium
sulphate). Evaporation under reduced pressure followed by chromatography
(silica gel column, using ether/petrol, 20%, followed by ether as eluent)
gave the quinone as a pure crystalline solid.
Conversion of 2-Naphthol to 1,2-Naphthoquinone
Using the above method 2-naphthol (72 mg, 0.5 mmol) was converted
to 1,2-naphthoquinone (51 mg, 63%) m.p. 144-6; (lit.5 m.p. 145-6°).
Conversion of 1-Naphthol to 1,2-Naphthoquinone
Using the general method 1-naphthol (72 mg, 0.5 mmol) was converted
to 1,2-naphthoquinone (50 mg, 62%) m.p. 146-7° (lit.5 m,p. 145-6°).
Conversion of Thymol to 3-Methy1-6-Isopropy1-1,2-BenZoquinone (1,2-Thymo-
quinone).
Using the general method thymol (75 mg, 0.5 mmol) was converted
to 1,2-thymoquinone (49 mg, 59%) m.p. 60-61°,v (Nujol): 1680 cm-1, max.
T (CDC13): 3.0-3.6 (2H, m), 6.6-7,2 (1H, m), 7.8 (3H, s), 8.7 (3H, s),
and 8.8 (3H, s),
m/e: 166 (M+), (Found: C, 73,26; H, 7.50; C10H1202
requires C, 73.20; _
Amax. (Et0H): 273 (e 2375) and 415 ( 1770) nm,
H, 7,32%).
104.
Conversion of Carvacrol to 1,2-Thymoquinone
Using the general method,. carvacrol (75 mg, 0.5 mmol) was converted
to 1,2-thymoquinone (50 mg, 60%) m.p. 60-61°.
Conversion of 2,4-Di-I:-Butylphenol to 3,5-Di-t-Butylbenzoquinone
Using the general method, 2,4-di-t-butylphenol (103 mg, 0.5 mmol)
was converted to 3,5-di-t-butylbenzoquinone (74 mg, 68%) m.p. 108-112°
(lit.11 m.p. 114°).
Reaction of 2,4-Di-t-Butylphenol with Benzeneseleninyl Chloride
A solution of 2,4-di-t-butylphenol (103 mg, 0.5 mmol) in dry THF
(5 ml) at -780 was treated with a solution of benzeneseleninyl chloride
(105 mg, 1 equiv) in THF (5 ml) and the mixture was allowed to warm to
room temperature. P.l.c. (on silica gel, using ether/petrol, 20% as eluent)
gave 3,5-di-t-butylbenzoquinone (24 mg, 22%) and unreacted starting
material (56 mg, 54%) as the only identifiable materials.
Attempted Trapping of Intermediate (18)
(i) A solution of 2,4-di-t-butylphenol (103 mg, 0.5 mmol) in dry THF
(5 ml) was treated with sodium hydride (80% suspension in oil, 23 mg, 1.5
equiv.) to give the anion. A solution of benzeneseleninyl chloride (105 mg,
1 equiv.) in THF (5 ml) was added at -78° and the reaction mixture was
allowed to warm to room temperature.
Treatment of the resulting solution with benzenethiol (500 mg)
gave no catechol-type products, as monitored by t.l.c. Addition of lithium
cyanide (150 mg) gave no catechol products after stirring for 12 h.
(ii) A solution of 2,4-di-t-butylphenol (103 mg, 0.5 mmol) in THF
105.
(5 ml) was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol)
and the mixture was stirred for 3 h. Filtration and chromatography gave
diphenyldiselenide (82 mg, 52%) as the only identifiable product.
Treatment of the reaction mixture with either benzenethiol (500 mg)
or lithium cyanide (150 mg) gave no catechol-type products.
(iii) A solution of 2,4-di-t-butylphenol (103 mg, 0.5 mmol) in THF
(5 ml) at 50o was treated with lithium cyanide (150 mg) and benzeneseleninic
anhydride (180 mg, 0.5 mmol). T.l.c. analysis showed that 3,5-di-t-butyl-
benzoquinone was the major product, and no catechols could be detected.
Attempted Preparation of Intermediate (18)
(i) A stirred solution of 3,5-di-t-butylcatechol (111 mg, 0.5 mmol)
in THF (5 ml) was treated with sodium hydride (80% suspension in oil,
20 mg, 1.3 equiv.) to form the monoanion. A solution of benzeneselenenyl
chloride (95 mg, 0.5 mmol) was added and stirring was continued for 2 h.
Chromatography (silica gel column, using ether/petrol, 10% as eluent)
gave 3,5-di-t-butylbenzoquinone (42 mg, 38%) as the only identifiable
product,
(ii) A solution of 3,5-di-t-butylcatechol (111 mg, 0.5 mmol) in THF
(5 ml) was treated with pyridine (1 ml) and benzeneselenenyl chloride
(95 mg, 0.5 mmol). Filtration and chromatography (silica gel column,
using ether/petrol, 10% as eluent gave 3,5-di-t-butylbenzoquinone (86 mg,
78%) as the only identifiable product.
Phenylselenation using Intermediate (18)
A solution of 2,4-di-t-butylphenol (103 mg, 0.5 mmol) in THF (5 ml)
was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol) and the
reaction mixture was stirred for 2 h. 2-Naphthol (72 mg, 0,5 mmol) was
106.
added and after 15 min, p.1,c. (on silica gel, using ether/petrol, 10% as
eluent) yielded 1-phenylseleno-2-naphthol (27 mg, 18%).
Attempted Trapping of Intermediate (18) as the Catechol Diacetate
A solution of 2,4-di-t-butylphenol (103 mg, 0.5 mmol) in THF (5 ml)
was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol) and the
reaction mixture was stirred for 2 h. Zinc (200 mg), acetic acid (3 drops),
acetic anhydride (3 ml) and pyridine (1 drop) were added and t.l.c.
analysis showed no catechol diacetate to be present.
Other Attempted Conversions of Phenols to o-Quinones
Using the general method, 2,4-xylenol (61 mg, 0.5 mmol), 3,4-xylenol
(61 mg, 0,5 mmol), o-cresol (56 mg, 0.5 mmol), o-nitrophenoi (70 mg,
0,5 mmol), resorcinol (55 mg, 0.5 mmol) and phloroglucinol (63 mg, 0.5 mmol)
all gave intractable mixtures of products from which no o-quinones could
be isolated.
Oxidation of 4-t-Butylphenol with Benzeneseleninic Anhydride
A solution of 4-t-butylphenol (75 mg, 0.5 mmol) in THF (5 ml) was
treated with benzeneseleninic anhydride at 50° in the usual way. A mixture
of products was observed. P.l.c. (on silica gel, using ether/petrol, 10%
as eluent) gave 4-t-buty1-6-phenylseleno-1,2-benzoquinone (6 mg, 4%) m.p.
11920° (lit.7 m.p. 120°).
4-Phenylseleno-1,2-Naphthoquinone (28)
A solution of 2-naphthol (72 mg, 0.5 mmol) in THF (5 ml) at 50°
was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol) and the
mixture was stirred for 24 h. Filtration and p.l.c. (on silica gel using
107.
ether/petrol, 10% as eluent) gave 4-phenylseleno-1,2-naphthoquinone (3 mg,
2%) m.p. 169-171° (lit.7 m.p. 172° (dec)).
Attempted Phenylselenation of 1,2-Naphthoquinone
(i) Using diphenyldiselenide: A solution of 1,2-naphthoquinone
(13 mg, 0.1 mmol) in THF (8 ml) was treated with diphenyldiselenide
(157 mg, 5 equiv.) at room temperature. After 24 h no phenylselenated
quinone could be detected by t.l.c.
(ii) Using diphenylseleninylselenenate (15): A solution of 1,2-
naphthoquinone (13 mg, 0.1 mmol) in THF (5 ml) was added to a solution
of reagent (15), (5 equiv.) and the mixture was stirred for 24 h. P.l.c.
(on silica gel, using ether/petrol, 10% as eluent) gave the phenyl-
selenonaphthoquinone (1.2 mg, 4%) m.p. 169-170° m.p. 172°).
(iii) Using diphenyldiselenide and mCPBA: The pale yellow solution
formed by reaction of diphenyldiselenide (157 mg, 0.5 mmol) with mCPBA
(180 mg, 1.0 mmol) in THF (8 ml) was treated with a solution of 1,2-
naphthoquinone (13 mg, 0.1 mmol) in THF (3 ml) and the mixture was stirred
for 24 h. No phenylselenoquinone could be detected by t.l.c.
(iv) Using benzeneseleninic anhydride: A solution of 1,2-naphtho-
quinone (13 mg, 0.1 mmol) in THF (5 ml) was treated with benzeneseleninic
anhydride (180 mg, 0.5 mmol) and the mixture was stirred for 24 h.
Filtration and p.l.c. (on silica gel, using ether/petrol, 10% as eluent)
gave the phenylselenoquinone (0.9 mg, 30) m.p. 169-170° (lit.7 m.p.
172°)
Oxidation of 3,5-Di-t-Butylcatechol with Benzeneseleninic Anhydride
A solution of 3,5-di-t-butylcatechol (111 mg, 0.5 mmol) in THF
108.
• (5 ml) was treated at room temperature with benzeneseleninic anhydride
(180 mg, 0.5 mmol). After 15 min the reaction mixture was filtered and
chromatographed (silica gel column, using petrol/chloroform mixtures as
eluents) to give 3,5-di-t-butylbenzoquinone (96 mg, 88%) m.p. 109-112°
(lit.11 m.p. 114
o).
Oxidation of catechol with Benzeneseleninic Anhydride
A solution of catechol (55 mg, 0.5 mmol) in THF (5 ml) was treated
at room temperature with benzeneseleninic anhydride (180 mg, 0.5 mmol).
An immediate reaction occurred but no identifiable products could be
isolated by chromatography.
Oxidation of 2,6-Dimethylhydroouinone with Benzeneseleninic Anhydride
A solution of 2,6-dimethylhydroquinone (69 mg, 0.5 mmol) in THF
(5 ml) was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol) at
room temperature. Further oxidant (ca. 0.2 mmol) was added until t.l.c.
showed complete disappearance of quinol. The reaction mixture was filtered
and, after p.l.c. (on silica gel using ether/petrol, 10% as eluent) gave 2,6-
diMethylbenzoquinone (60 mg, 88%) m.p. 71-73° (lit.5 m.p. 72-73°).
Oxidation of Hydroquinone using Benzeneseleninic Anhydride
A solution of hydroquinone (55 mg, 0.5 mmol) in THF (5 ml) was
treated with benzeneseleninic anhydride (180 mg, 0.5 mmol) at room tempera-
ture, Filtration and p.l.c. (on silica gel using ether/petrol, 10% as
eluent) gave benzoquinone (45 mg, 84%) m.p. 114-116° (lit.5 m.p. 115-117°).
Oxidation of 1,4-Dihydroxynaphthalene with Benzeneseleninic Anhydride
A solution of 1,4-dihydroxynaphthalene (80 mg, 0.5 mmol) in THF
109.
(5 ml) was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol) at
room temperature. Work-up in the usual way gave naphthoquinone (73 mg,
92%) m.p. 123-124° (lit.5 m.p. 125°).
Formation of Selenoimine (34) using Sodium Hexamethyldisilazide
A solution of 2,4-xylenol (25 mg, 0.2 mmol) in dry toluene (2 ml) was
treated with sodium hexamethyldisilazide (60 mg, 0.3 mmol, 1.5 equiv.)
and benzeneseleninic anhydride (75 mg, 0.2 mmol) under nitrogen with
stirring. A deep red colour developed. After 45 min the mixture was
poured into water (5 ml) and extracted with chloroform (2 x 5 ml). Chro-
matography (silica gel column, using ether/petrol, 20% as eluent) yielded
the selenoimine (34), (22 mg, 38%) m.p. 120-1° (lit.7 m.p. 120-10).
Formation of Selenoimine (34) using Hexamethyldisilazane
A solution of 2,4-xylenol (25 mg, 0.2 mmol) in dry benzene (2 ml) was
treated with hexamethyldisilazane (35 mg, 1.1 equiv) and benzeneseleninic
anhydride (75 mg, 0.2 mmol). Chromatography (silica gel column, using
ether/petrol, 20% as eluent) gave selenoimine (34), (35 mg, 61%).
Optimisation of Selenoimine Formation
Formation of selenoimine (34) was repeated, varying the reaction
conditions:
(i) 2,4-xylenol (25 mg, 0.2 mmol) was treated with hexamethyldisilazane
(35 mg, 1.1 equiv) and benzeneseleninic anhydride (25 mg, 0.33 equiv.)
to give selenoimine (34), (13 mg, 23%).
(ii) 2,4-xylenol (25 mg, 0.2 mmol) was treated with hexamethyldisilazane
110.
(35 mg, 1.1 equiv.) and benzeneseleninic anhydride (150 mg, 2 equiv.) to
give selenoimine (34), (37 mg, 6496);
(iii) 2,4-xylenol (25 mg, 0.2 mmol) was treated with hexamethyldisilazane
(70 mg, 2.2 equiv.) and benzeneseleninic anhydride (75 mg, 1 equiv.) to
give selenoimine (34), (37 mg, 64%);
(iv) 2,4-xylenol (25 mg, 0.2 mmol) was treated with hexamethyldisilazane
(70 mg, 2.2 equiv.) and benzeneseleninic anhydride (150 mg, 2 equivs.) to
give selenoimine (34), (41 mg, 70%);
(v) 2,4-xylenol (25 mg, 0.2 mmol) was treated with hexamethyldisilazane
(35 mg, 1.1 equivs.) and benzeneseleninic anhydride (75 mg, 1 equiv.) with
strict exclusion of laboratory light. Selenoimine (34) was again isolated
(35 mg, 61%) after 45 min.
With oxygen bubbled through the reaction mixture the same yield of
selenoimine was obtained.
General Method of Formation of Selenoimines
A solution of the phenol (0.5 mmol) in dry benzene (3 ml) was treated
with hexamethyldisilazane (88 mg, 1.1 equiv.) and benzeneseleninic an-
hydride (180 mg, 0.5 mmol) at room temperature, with stirring. After 30
mins the reaction mixture was diluted with chloroform (10 ml) and filtered.
P.1,c. (on silica gel, using ether/petrol mixtures as eluents) gave the
selenoimine as a crystalline solid.
Conversion of Phenol to Selenoimine (35)
Using the general method, phenol (47 mg, 0.5 mmol) was converted
to selenoimine (35), (59 mg, 45%), m.p. 75-76°, vmax. (Nujol): 1630,
1580, 1520, and 760 cm-1
, T: 3.0-3.3 (2H, m) and 2.0-2.9 (7H, m), Xmax.:
460 (e 3000 ) and 260 ( 2100 ) nm, m/e: 261 (M+), (Found:
C, 55.06; H, 3.46; N, 5.25. C12H9NOSe requires C, 55.0; H, 3.3; N, 5.3%).
Selenoimine (41) was also isolated as an unstable orange oil, and
tPis was immediately treated with zinc (50 mg), acetic acid (2 drops)
acetic anhydride (1 ml) and pyridine (1 drop) to give 4-aminophenol-
N,0-diacetate (9 mg, 10%), m.p. 148-150° (lit5 m.p. 150-157°).
Conversion of Carvacrol to Selenoimine (36)
Using the general method, carvacrol (75 mg, 0.5 mmol) was converted
to selenoimine (36), (92 mg, 58%), m.p. 59-60°, vmax.
1610 cm1, T:
2.0-3.8 (7H, m), 6.3-6.9 (1H, m), 8.0 (3H, s), 8.7 (3H, s), and 8.8 (3H,
s).Xmax.
264 (e 3300), 435 ( 11000), and 473 (9200)nm, m/e 319 (Mt)
(Found: C, 60.66; H, 5.27; N, 4.36. C1e17
NOSe requires C, 60.4; H, 5.3;
N, 4.4%).
Conversion of Thymol to Selenoimine (37)
Using the general method, thymol (75 mg, 0.5 mmol) was converted to
selenoimine (37), (89 mg, 56%), m.p. 39-40°, vmax. 1610 cm-1, T: 2.0-
3.7 (7H, m), 6.6-7.0 (1H, m), 7.6 (3H, s), 8.8 (3H, s), and 8.9 (3H,
0,A max, 272 (e 3250), 433 (9600), and 468 (10150) nm, m/e: 319 (Ml.),
(Found: C, 60.25; H, 5.30; N, 4.12. C16H17
NOSe requires C, 60.4; H, 5.3;
N, 4.4%).
Reductive Acetylation of Selenoimines (36) and (37)
(i) Selenoimine (36): The selenoimine (32 mg, 0,1 mmol) was dissol-
ved in acetic anhydride (2 ml), Zinc dust, (60 mg), acetic acid (3 drops)
and pyridine (1 drop) were then added. A vigorous reaction set in which
was moderated by ice cooling, The reaction mixture was diluted with
112.
chloroform (20 ml), filte-r.ed, washed with aqueous sodium bicarbonate
solution (2 x 20 ml) and water (20 ml), dried (anhydrous sodium sulphate)
and evaporated under reduced pressure. Trituration of the residual oil,
first with petrol then with ether gave the N,0-diacetate (18 mg, 81%)
m.p. 224-226°.
An authentic sample was prepared by nitrating thymol at -10° with
a four fold excess of nitric acid in acetic acid (20% solution). Steam
distillation gave the o-nitrophenol which was reductively acetylated with
zinc, acetic anhydride, acetic acid and pyridine to give the N,0-diacetate
(74%) m.p. 228-30°, The melting point was undepressed on admixture with
the material prepared by reductive acetylation of the selenoimine.
(ii) Selenoimine (37): The N,0-diacetate was prepared in the usual
way and compared (m.p. and mixed melting-point) with an authentic sample
prepared via the nitrophenol, as above.
N,O,diacetate from selenoimine (37) m.p. 164-166°
N,0-diacetate from nitrophenol m.p. 160-163°
Reduction of Selenoimine (34) to 6-Amino-2,4-Xylenol
(i) A solution of selenoimine (34), (15 mg, 0,05 mmol) in dry benzene
(2 ml) was treated with benzenethiol (0.3 ml). After 4 h, the mixture
became colourless and p.l,c. (on silica gel, using petrol/chloroform, 50%
as eluent) yielded the crude aminoxylenol (6 mg, 85%) as an oil, vmax.
3300 and 3400 cm-1, m/e: 137 (Mt).
(ii) A solution of selenoimine (34), (15 mg, 0.05 mmol) in dry ben-
zene (2 ml) was treated with thioglycollic acid (0.5 ml). After 12 h
the mixture became colourless and p.l.c. (on silica gel, using petrol/
chloroform, 50% as eluent) yielded the crude aminoxylenol (2.8 mg, 40%),
113.
as an oil.
(iii) A solution of selenoimine (34), (3 mg) in dry benzene (1 ml)
remained unchanged after 12 h passage of hydrogen sulphide gas.
Conversion of 2,6-Xylenol to Selenoimine (42)
(i) A solution of 2,6-xylenol (25 mg, 0.2 mmol) in dry benzene (2m1)
was treated with hexamethyldisilazane (35 mg, 1.1 equiv.) and benzene-
seleninic anhydride (75 mg, 0.2 mmol). A deep orange colour was produced.
P.l.c. (on silica gel, using ether/petrol, 20% as eluent)gave selenoimine
(42) as orange needles (27 mg, 48%), m.p. 140-141°, (lit.7, m.p. 140-141°).
Conversion of Monocathylate (43) to Selenoimine (42)
A solution of monocathylate (42 mg, 0.2 mmol) in dry benzene (3 ml)
was treated with sodium hexamethyldisilazide (60 mg, 1.5 equiv.) and benz-
eneseleninic anhydride (75 mg, 0.2 mmol). The reaction mixture was diluted
with chloroform (10 ml) and washed with water (10 ml). The organic phase
was dried (anhydrous sodium sulphate) and after p.l.c. (on silica gel,
using ether/petrol, 20% as eluent) gave selenoimine (42), (25 mg, 28%).
Conversion of Monocathylate (44) to Selenoimine (45)
A solution of hydroquinone monocathylate (44), (91 mg, 0.5 mmol) was
treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and benzenesele-
ninic anhydride (180 mg, 0.5 mmol). Filtration followed by p.l.c. (on
silica gel, using ether/petrol, 20% as eluent) gave the selenoimine (45),
(47 mg, 45%), m.p. 66-68°, vmax.(Nujol): 1740 and 1615 cm-1, T: 2.0-
2.6 (6H, m), 2.7-3.4 (2H, ABq, J = 9Hz), 5.5-5.9 (2H, q), and 8.6 (3H, t),
Xmax. 260 (e 5500), 410 (4000), and 464 (11000) nm, m/e: 210 (M)
114.
(Found: C, 51,53; H, 3.94; N, 3.98, C15H13N04Se requires C, 51.5;
H, 3.7; N, 4.0%).
Attempted Conversion of 1,2-Thymoquinone to Selenoimine (36)
A solution of 1,2-thymoquinone (82 mg, 0.5 mmol) in dry benzene
(3 ml) was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and
benzeneseleninic anhydride (180 mg, 0.5 mmol). After 3 h, t.l.c. showed
that no selenoimine (36) was present in the reaction mixture. Chromatogra-
phy yielded a mixture of unidentifiable products.
Conversion of 1-Naphthol to Selenoimines (47) and (48)
A solution of 1-naphthol (72 mg, 0.5 mmol) in dry benzene (3 ml) was
treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and benzeneseleni-
nic anhydride (180 mg, 0.5 mmol). After 30 min the reaction mixture was
filtered and p.l.c. (on silica gel, eluting three times with ether/petrol
5%) gave (i) selenoimine (47), (77 mg, 49%), m.p. 164-166° (lit.7, m.p.
164°, and (ii) selenoimine (48), (26 mg, 17%), m.p. 124-126° (lit.7
m.p, 126-7°).
Conversion of 2-Naphthol to Selenoimines (47) and (48)
A solution of 2-naphthol (72 mg, 0.5 mmol) in dry benzene (3 ml)
was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and benzene-
seleninic anhydride (180 mg, 0.5 mmol). After 30 min the reaction mixture
was filtered and p.l.c. (on silica gel, eluting three times with ether/
petrol, 5%) gave (i) selenoimine (47), (38 mg, 24%), m.p. 164-1660 and
(ii) selenoimine (48), (57 mg, 37%), m.p. 124-126°.
115.
Conversion of 1,2-1aphthoquinone to Selenoimines (47) and (48)
A solution of 1,2-naphthoquinone (79 mg, 0.5 mmol) in dry benzene
(3 ml) was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and
benzeneseleninic anhydride (180 mg, 0.5 mmol). After 30 min the reaction
mixture was filtered and p.l.c. (on silica gel, eluting three times with
ether/petrol, 5%) gave (i) selenoimine (47), (54 mg, 35%), m.p. 164-
166o and (2) selenoimine (48), (16 mg, 10%), m.p. 124-126°.
Formation of Selenoimine (34) using Benzeneselenenyl Chloride
A solution of 2,4-xylenol (61 mg, 0.5 mmol) in dry benzene (3 ml)
was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and ben-
zeneselenenyl chloride (95 mg, 0.5 mmol) at room temperature with stirring.
After 35 min, the reaction mixture was filtered and p.l.c. (on silica
gel, using ether/petrol, 20% as eluent) afforded selenoimine (34), (58mg,
40%), m.p. 120-121o, (lit.7 m.p. 120-1°).
Formation of Selenoimine (34) using Benzeneseleninic Acid
A solution of 2,4-xylenol (61 mg, 0.5 mmol) in dry benzene (3 ml)
was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and benzene-
seleninic acid (95 mg, 0.5 mmol) at room temperature with stirring. After
45 min the reaction mixture was filtered and p.l.c. (on silica-gel, using
ether/petrol, 20% as eluent) afforded selenoimine (34), (36 mg, 25%),
m,p, 120r,121° (lit.7 m.p. 120-121°).
Formation of Selenoimine (34) using Ammonia
A solution of 2,4-'xylenol (61 mg, 0.5 mmol) in dry THE (3 ml) was
treated with liquid ammonia (3 ml) with careful exclusion of moisture.
116.
Benzeneseleninic anhydride (180 mg, 0.5 mmol) was added and the
mixture was stirred at room temperature until all the excess ammonia had
evaporated. Filtration and p.l.c. (on silica-gel, using ether/petrol,
20% as eluent) afforded selenoimine (34), (1.5 mg, 1%) and unreacted
2,4-,,xylenol (48 mg, 79%) as the only identifiable products.
Attempted Formation of Selenoimine (34) using t-Butylamine
A solution of 2,4-xylenol (61 mg, 0.5 mmol) in dry benzene (3 ml)
was treated with t-butylamine (40 mg, 1.1 equiv.) and benzeneseleninic
anhydride (180 mg, 0.5 mmol). After 12 h, t.l.c. indicated that no
selenoimine (34) had been formed.
Preparation of. Tris-(trimethylsily1)-amine (49)
A solution of sodium hexamethyldisilazide (1.85 g, 10 mmol) in dry
toluene (5 ml) was treated with trimethylsilylchloride (1.1 g, 10 mmol)
and the mixture was heated to reflux for 18 h. Fractional vacuum
distillation of the resulting solution gave the tris-reagent (49), (1.4 g,
60%) as a white waxy solid, m.p. 69-70° (lit.23 m.p. 69-71°).
Formation of Selenoimine (42) using Tris-(trimethylsily1)-amine
A solution of 2,6-xylenol (61 mg, 0.5 mmol) in dry benzene (3 ml)
was treated with tris-(trimethylsily1)-amine (125 mg, 1.1 equiv.) and
benzeneseleninic anhydride (180 mg, 0.5 mmol). After 1 h the reaction
mixture was filtered and p.l.c. (on silica-gel, using ether/petrol, 20%
as eluent) gave selenoimine (42), (27 mg, 19%), m.p. 140-141° (lit.7,
m,p. 140-141°).
117.
• Attempted Formation of Selenoimine (34) using Tris-(trimethylsily1)-amine
and Benzeneselenenyl Chloride
A solution of 2,4-xylenol (61 mg, 0.5 mmol) in dry benzene (3 ml)
was treated with tris-(trimethylsilyl)-amine (125 mg, 1.1 equiv.) and
benzeneselenenyl chloride (95 mg, 0.5 mmol) with stirring at room
temperature. After 45 min the reaction mixture was filtered and p.l.c.
(on silica gel, using ether/petrol, 20% as eluent) gave a mixture of
unidentifiable products. No selenoimine (34) could be detected.
Reaction of Hexamethyldisilazane with Benzeneseleninic Anhydride
A solution of hexamethyldisilazane (163 mg, 1 mmol) in dry THF
(5 ml) was treated with benzeneseleninic anhydride (360 mg, 1.0 mmol) at
room temperature with stirring, A faint yellow colour was produced after
1 h, shown by t.l.c. to be due to formation of a trace of diphenyl-
diselenide. After 12 h, the reaction mixture was filtered to remove
O unreacted benzeneseleninic anhydride (342 mg, 95%) m.p. 164-5°, (lit.9
m t p, 164°) and distillation of the filtrate gave unreacted hexamethyl-
disilazane (150 mg, 92%).
The reagents (same quantities) were mixed with toluene (1 ml) in
a sealed tube and heated at 100° for 18 h. Benzeneseleninic anhydride
(346 mg, 96%) and hexamethyldisilazane (155 mg, 95%) were recovered
unchanged. Diphenyldiselenide (6 mg, 2%) was isolated from the reaction
mixture by chromatography (silica-gel column, eluting with petrol).
Reaction of Benzeneseleninic Anhydride with Tris-(trimethylsily1)-amine
A solution of tris-(trimethylsily1)-amine (125 mg, 0.53 mmol) in
dry THF (5 ml) was treated with benzeneseleninic anhydride (180 mg, 0.5
mmol) at room temperature with stirring. After 12 h, t.l.c. showed
118.
that no reaction had occurred and filtration gave unreacted benzene-
seleninic anhydride (167 mg, 93%). The silazane was recovered (119 mg,
95%) by chromatography (silica-gel column, eluting with chloroform).
Reaction of Hexamethyldisilazane with Benzeneselenenyl Chloride
A solution of hexamethyldisilazane (1.63 g, 10 mmol) in dry THF
(5 ml) was treated with a solution of benzeneselenenyl chloride (1.90 g,
10 mmol) in THF (3 ml) at room temperature. An immediate reaction
occurred to give a mixture of unidentifiable products. Diphenyldiselenide
(0,86 g, 5596) was isolated by chromatography (silica-gel column, eluting
With petrol),
The reaction was repeated at 0° but no difference was noted.
Reaction of Sodium Hexamethyldisilazide with Benzeneselenyl Chloride
A solution of benzeneselenenyl chloride (95 mg, 0.5 mmol) in dry
THF (5 ml) was treated with sodium hexamethyldisilazide (93 mg, 0.5 mmol)
at room temperature, with stirring. A rapid reaction took place to give
a mixture of unidentifiable products. Diphenyldiselenide (43 mg, 55%)
was isolated by chromatography (silica-gel column, using petrol as eluent).
The reaction was repeated at -10° and 0° but the same mixture of
products was obtained.
Benzeneselenium Trichloride
A solution of diphenyldiselenide (314 mg, 1 mmol) in hexane (3 ml)
was treated with sulphurylchloride (500 mg, 3.7 mmol), dropwise with
stirring, A white precipitate of benzeneselenium trichloride was formed.
Filtration followed by air drying (vacuum drying causes decomposition)
119.
gave the trichloride (430 mg, 80%) as a white powder, m.p. 130-132° (lit 4
m.p. 133-134°) which was stored in a desiccator over P205.
Reaction of Benzeneselenium Trichloride with Tris-(trimethylsilyl)-amine
A solution of tris-(trimethylsilyl)-amine (125 mg, 0.53 mmol) in
dry THF (5 ml) was treated at room temperature with benzeneselenium
trichloride (131 mg, 0.5 mmol) with stirring. After 12 h, t.l.c.
showed that no reaction had occurred. The reaction mixture was warmed
at 50o for 3 h, but again no reaction was observed. The solvent was
distilled off and the solid residue was triturated with hexane (2 x 5 ml).
Filtration gave the unreacted benzeneselenium trichloride (112 mg, 86%),
and evaporation of the filtrate gave crude tris-(trimethylsilyl)-amine
(115 mg, 92%). Diphenyldiselenide was shown by t.l.c. to be present
in trace amounts.
Reaction of Benzeneseleninic Anhydride with Hexamethyldisilazane in the
Presence of Boron Trifluoride
A suspension of benzeneseleninic anhydride (180 mg, 0,5 mmol) in
dry THF (5 ml) was treated with boron trifluoride etherate (70 mg, 1 equiv.)
The anhydride immediately dissolved. Hexamethyldisilazane (81 mg, 0.5 mmol)
was added and the mixture was stirred for 1 h. T.l.c. indicated that
no reaction had occurred. The solution was evaporated under reduced
pressure to give an oily solid. Trituration with petrol followed by fil-
tration yielded unreacted benzeneseleninic anhydride (170 mg, 94%).
Formation of Selenoimine (34) using Benzeneseleninyl Chloride
A solution of 2,4-xylenol (61 mg, 0,5 mmol) in dry THF (3 ml) was
treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and a solution of
120.
benzeneseleninyl chloride (103 mg, 0.5 mmol) in dichloromethane (5 ml)
was added dropwise, with stirring. After 40 min, the mixture was
concentrated under reduced pressure and p.l.c. (on silica-gel, using
ether/petrol, 15% as eluent) afforded selenoimine (34), (26 mg, 18%)
In e p t 120121°, (lit.7 m.p. 120-121°).
Reaction of Lithium Hexamethyldisilazide with Benzeneseleninyl Chloride
A solution of benzeneseleninyl chloride (103 mg, 0.5 mmol) in
dry dichloromethane (10 ml) was treated with lithium hexamethyldisilazide
(85 mg, 1 equiv.) with stirring, at room temperature. After 10 min, a
white precipitate of lithium chloride appeared. Filtration gave a colour-
less solution, which rapidly decomposed on concentration under reduced
pressure, Chromatography (silica-gel column, using petrol as eluent) gave
diphenyldiselenide (61 mg, 78%) as the only identifiable product.
The same reaction was performed in the presence of 2,6-di-t-butyl- ___
phenol (103 mg, 0,5 mmol). Diphenyldiselenide (40 mg, 51%.\ was again
obtained as the major product. 3,3,5,5-Tetra-t-butylbiphenoquinone (52)
(22 mg, 24%) was also isolated as yellow crystals, m.p. 227-228° (lit.25
m,p, 240241°), Amax.: 420 (c 35 000), 269 (3 000), 259 (3 500) and
249 (3680) nm, (lit.25 Amax.: 427 (66 000), 271 (4240), 262 (4800), and
253 (4320) nm, m/e 411 (Mt)).
Reaction of 2,6-Di-t-Butylphenol with Hexamethyldisilazane and Benzenesele-
ninic Anhydride
A solution of 2,6-di-t-butylphenol (103 mg, 0.5 mmol) in dry THE
(5 ml) was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and
benzeneseleninic anhydride (180 mg, 0.5 mmol) at room temperature, with
stirring. After 45 min, the reaction mixture was filtered and p.l.c.
121.
(on silica gel using petrol as eluent) gave (i) diphenyldiselenide (97 mg,
62%) and (ii) 3,3,5,5-tetra-t-butylbiphenoquinone (40 mg, 39%), m.p.
226n2280 (lit.25 m.p. 240-241o). No selenoimines could be detected.
Reaction of Benzeneseleninyl Chloride with Ammonia
A solution of benzeneseleninyl chloride (103 mg, 0.5 mmol) in dry
dichloromethane (10 ml) was treated with liquid ammonia (redistilled,
2 ml) and the reaction mixture was allowed to warm to room temperature.
After 20 min a white precipitate of ammonium chloride was observed.
When no ammonia remained in the solution, the reaction mixture was filtered
under nitrogen to give a pale yellow solution. Concentration under
reduced pressure caused the yellow solution to decompose to a red/black
oil, Storage of the yellow solution at 4° for 1 week did not cause any
product to crystallise. Addition of petrol was similarly unsuccessful.
Formation of Selenoimine (34) using Benzeneseleninyl Chloride and Ammonia
Using the method described above, benzeneseleninyl chloride (103
mg, 0.5 mmol) was treated with liquid ammonia (2 ml) to give after filtra-
tion, a clear pale yellow solution. A solution of 2,4-xylenol (61 mg,
0,5 mmol) in dichloromethane (3 ml) was added and the reaction mixture
was stirred at room temperature for 2 h. A pale red colour developed.
Concentration under reduced pressure followed by p.l.c. (on silica gel,
using ether/petrol, 20% as eluent) gave selenoimine (34), (6 mg, 4%),
ma), 120n121°, (lit.7 m.p. 120-1210).
Formation of Selenoimine (48) using Benzeneseleninyl Chloride and
Ammonia
To the pale yellow solution resulting from treatment of benzenese-
122.
leninyl chloride (103 mg, 0.5 mmol) with liquid ammonia (2 ml), (see above),
was added a solution of 2-naphthol (72 mg, 0.5 mmol) in dichloromethane
(3 ml). The mixture was stirred for 1 h, during which time a pale
orange colour developed. Concentration under reduced pressure, followed
by p.1,c. (on silica gel, eluting three times with ether/petrol, 5%) gave
selenoimine (48), (7.8 mg, 5%) m.p. 124-126° (lit.7 m.p. 126-127°). No
trace of selenoimine (47) could be detected.
Conversion of Benzhydrol to Benzophenone using Benzeneseleninic Anhydride
A solution of benzhydrol (92 mg, 0.5 mmol) in dry THF (15 ml) was
treated with benzeneseleninic anhydride (180 mg, 0.5 mmol). The mixture
was heated under reflux for 3 h, by which time t.l.c. showed complete
absence of benzhydrol. The solution was cooled to room temperature,
concentrated under reduced pressure and p.l.c. (on silica-gel using
ether/petrol, 5% as eluent) afforded benzophenone (77 mg, 85%) as white
crystals m.p. 47-49o (lit.
5 m,p. 49
o).
Conversion of Hydrobenzoin to Benzil using Benzeneseleninic Anhydride
A solution of hydrobenzoin (107 mg, 0.5 mmol) in dry THF (5 ml) was
treated with benzeneseleninic anhydride (360 mg, 1 mmol). The mixture
was heated under reflux for 3 h, by which time, t.l.c. showed complete
absence of hydrobenzoin. Benzoin was formed during the reaction but this
was subsequently oxidised further. the solution was cooled to room
temperature, concentrated under reduced pressure and p.l.c. (on silica
gel using ether/petrol, 5% as eluent) afforded benzil (81 mg, 77%) as
pale yellow crystals, m.p. 93-95°, (lit.5 m.p. 950).
123.
Conversion of Benzoin to Benzil using Benzenescloninic Anhydride
A solution of benzoin (106 mg, 0.5 mmol) in d22/ THE (15 ml ) was
treated with benzeneseleninic anhydride (180 mg, 0.5 mmol). The mixture
was heated under reflux for 3 h, by which time t.l.c. showed complete
absence of benzoin. The solution was cooled to room temperature, con-
centrated under reduced pressure and p.l.c. (on silica-gel, using ether/
petroleum, 5% as eluent) afforded benzil (96 mg, 92%) as pale yellow
crystals, m.p. 93-95°, (lit.5 m.p. 95°).
Conversion of Benzilic Acid to Benzophenone using Benzeneseleninic
Anhydride
A solution of benzilic acid (228 mg, 1 mmol) in dry toluene (10 ml)
was treated with benzeneseleninic anhydride (360 mg, 1 mmol). The
mixture was heated at 100° for 24 h. T.l.c. showed that most of the start-
ing material was still present. Addition of more oxidant had no notice-
able effect. The solution was cooled to room temperature, filtered and
concentrated under reduced pressure. P.l.c. (on silica-gel, using ether/
petrol, 5% as eluent)gave benzophenone (9 mg, 5% as a white crystalline
solid, m,p. 48-49o (lit.
5 m.p. 490).
Iodimetric Titration Procedure for Studying Phenol Oxidations with
Benzeneseleninic Anhydride
In a typical run, a solution of the phenol (0.25 mmol) in dry THE
(4 ml) was treated with benzeneseleninic anhydride (90 mg, 0.25 mmol)
with stirring at room temperature. To measure the oxidising ability of the
reaction mixture at a given time, the solution was quenched with dilute
sulphuric acid (2N, 10 ml) and extracted with diethylether (2 x 10 ml).
The aqueous phase was added to an acidic solution of potassium iodide
(0,5 g in 10 ml 2NH2SO4) and ethanol (10 ml) was added. The liberated
iodine was titrated with aqueous sodium thiosulphate solution (0.1 N)
124.
using starch indicator.
The diphenyldiselenide was recovered by column chromatography
(silica gel, using petrol as eluent).
The general procedure was also applicable where further reagents,
e,g, hexamethyldisilazane were present in the reaction mixture.
In order to recover the expected amount of diphenyldiselenide
from the hydroxylation reactions, it was found necessary to quench the
reaction mixture with an aqueous solution of potassium dihydrogen-
phosphate buffer solution (10%) instead of sulphuric acid.
The experimental results are tabulated in the Discussion section.
125.
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