The sanlfohaloform reaction. The stepwise conversion of ...

The sanlfohaloform reaction. The stepwise conversion of dialkyl sulfides into alkanesulfonyl chlorides

J. STUART GROSSERT AND RICHARD F. LANGLER Clzernistr? Department, Dall~ousie U~~i, ,ersi iy. Halifnx, N.S. , Canada B3H4J3

Received October 10, 1975l

J. STUART GROSSERT and RICHARD F. LAKGLER. Can. J. Chem. 55, 407 (1977). A thorough examination of the aqueous oxidative chlorination of 1,3,5-trithiane is described.

The results are utilized to explore and delineate the scope of a general, stepwise, oxidative cleavage reaction of dialkyl sulfides in which they are successively halogenated and oxidized to a-polychloros~~lfoxides; subsequently, these cleave to form sulfinyl chlorides, which hydrolyze and become further oxidized to yield alkanesulfonyl chlorides. The overall stepwise process is named the 'Sulfohaloform reaction' and the structural requirements of the substrates at each step are explored in detail. A practical, general synthesis of sulfonyl chlorides is presented.

J. STUART GROSSERT et RICHARD F. LANGLER. Can. J. Chem. 55, 407 (1977) On a examine la chloruration oxydative du trithiane-1,3,5 eEectuCe en phase aqueuse. On

utilise les resultats obtenus pour explorer et delimiter I'etendue d'une reaction de clivage oxydative generale qui s'opkre par etape et au cours de laquelle des sulfures de dialkyles sont successivement halogenes, oxydes en sulfoxyde d'a-polychlores et par la suite clivCs de facon a fournir des chlorures de sulfinyles qui par hydrolyse et oxydation subsequentes peuvent Ctre transformis en chlorures d'alkanesulfonyles. On a appele ce processus global par etape 'reaction sulfohaloforrnique' et on a determine en detail les conditions de structures du substrat qui sont necessaires B chaque etape. On presente une synthkse gCnCrale et pratique des chlorures de sulfonyle.

[Traduit par le journal]

Introduction Some time ago, we outlined ( I ) the preliminary

results from a study of the pathway by which 1,3,5-trithiane, 1, is converted upon treatment with molecular chlorine in aqueous media, into chloromethanesulfony1 chloride, CICH,~SO,~CI, 2. We now wish to report the results in detail.

In 1940, Lee and Dougherty (2) reexamined the chlorination of 1,3,5-trithiane 1 in aqueous medium, which had originally been reported on by Kostsova (3) in 1935. Lee and Dougherty concluded that 1,4-dichloro-2,3-dithiabutane might be an intermediate and showed that no sulfone could be intervening. In a subsequent study, Douglass et a/. (4) concluded that chloromethanesulfenyl chloride might be a short-lived intermediate.

Results and Discussion The Aqueous Chloriization of /,3,5-Trithiane

When we attempted to prepare 2 using the Lee and Dougherty procedure, it became obvious that 2 was grossly contaminated by other products and the mixture could not be separated

'Revision received September 20, 1976.

conveniently. The nature of these other products was revealed by carrying out a partial chlorination af 1, from which it was ascertained that no 2 had been formed but rather a number of intermediate products as detailed in Table 1. The results suggested the intermediacy of 1,3- dichloro-2-thiapropane, 3, and this was confirmed by exhaustive chlorination of 3 in aqueous acetic acid from which 2 was isolated in 70z yield. Since Lee and Dougherty had already shown that oxidative chlorination of sulfides into sulfonyl chlorides did not proceed via sulfones, it became apparent that a study of the pathway of this conversion could be fruitful. In particular, the question as to whether C-S bond cleavage and S-CI bond formation occurred at the sulfenyl or sulfinyl oxidation level was intriguing. Answers to these questions were obtained from a detailed examination of what emerged as a stepwise pathway by which the dichlorosulfide 3 is converted into the sulfonyl chloride 2 upon chlorination in aqueous medium. The study began with chlorination of the dicl~lorosulfide 3 in glacial acetic acid with varying water-sulfide ratios. This reaction provided the results shown in Scheme I .

CAN. J. CHEM. VOL. 55. 1977

TABLE 1. Products from partial chlorination of 1,3,5-trithiane (1 mol) in glacial acetic acid containing water (5 mol)

Number of moles Yield Product* Yield (g) isolated (%)

-

CHzO 0.52 0.14 14 Co2 0.57 0.11 11 CICH~OAC (41, 42) 2.29 0.18 18 ClCH,.O.CH,Cl (43, 44) 1 .49 0.11 22 CICH2.S.CH2Cl 3 (40) 8.00 0.53 53 C1CH2.SS.CH2CI i. 0.06 6 Unreacted (CH2S), 1 1.00 0.06 6

"NO CCI,, CHCl,, CH~CII, HC02H, CICH2.S02.CI, or ClCH2.S.CI was detected TYleld determined on a separate run.

These experiments conclusively established 1,3-dichloro-2-thiapropane-2-oxide, 4, as the next intermediate in the sequence. In a similar manner, chlorination of the dichlorosulfoxide 4 established the intermediacy of 1,1,3-trichloro- 2-thiapropane-2-oxide (CI,CH.SO.CH,CI, 5) as the subsequent intermediate.

When the trichlorosulfoxide 5 was chlorinated in aqueous acetic acid, only chloromethanesulfonyl chloride, 2, could be obtained. Although Lee and Dougherty (2) had demonstrated that some sulfones were inert to chlorine-water oxidation, we prepared 1,1,3-trichloro-2-tl~ia- propane-2,2-dioxide and subjected it to chlorination in aqueous acetic acid, from which it was recovered unchanged. Hence it was clear that the intermediate sulfoxide(s) must have reacted with chlorine and cleaved to furnish chloromethanesulfinyl chloride, 6 . Since sulfinyl chlorides are readily hydrolyzed to sulfinic acids ( 5 ) , it would have been futile to attempt the isolation of 6 from aqueous medium. When the trichlorosulfoxide 5 was chlorinated in dry acetic acid, chloron~ethanesulfinyl chloride, 6, could be observed in the nmr of the crude reaction mixture. This was demonstrated by adding authentic 6 to a sample of the crude and following the change in intensity of the chloromethyl signal.

Attempts to isolate the sulfinyl chloride 6 from acetic acid solution were unsuccessful. However, further chlorination led to a good conversion of 6 to the sulfonyl chloride 2 which could be isolated without difficulty.

CI, CI,CH SO CHzCl HOAc r CICHL SO CI + CHCI,

6 (75%)

CICH, S02CI + 4cC1

In order to obviate the difficulties experienced in isolating 6 from acetic acid, the trichlorosulfoxide 5 was chlorinated in methylene chloride which permitted the isolation of 6 without complication.

A summary of the pathway for the conversion of 1,3,5-trithiane, 1, appears in Scheme 2. The grounds for including 1,1,1,3-tetrachloro-2- thiapropane-2-oxide, 7, in Scheme 2 are presented later.

Mechanisms of Suljid~ und Suljbxide Cl~louinu- fions

Mechanisms for the various steps outlined in Scheme 2 are available from previous work. The pathway by which 1,3-dichloro-2-thiapro-

GROSSERT AND LANGLER

pane, 3, is converted to the corresponding ylene chloride are the most direct evidence sulfoxide involves chlorosulfonium chloride salt available that the chlorination of sulfoxides 8 formation prior to nucleophilic attack by water proceeds through an intermediate species having on the sulfur atom of the sulfoniurn salt. This a sulfur-chlorine bond. reaction has ample precedent (6-10). The inter-

The Chloritie-itiduced C-S Cleat.nge Reactior~ oj ~nediacy of a species with a sulfur-chlorine bond is supported in a more direct fashion by later r-PoI~~c/i loros~~,foxi~/es

work in which chlorination of selected sulfides Although the reactions of sulfides and sulf-

has been shown to furnish sulfenyl chlorides oxides with chlorine to furnish cc-chloro com-

(1 1-18). pounds via Pummerer rearrangements and/or to hydrolyze to gi~te sulfoxides or sulfones had

The mechanism for the Pummerer rearrangement of chlorosulfoniurn chlorides has been carefally examined by Wilson et 01. (13, 14). The mechan~sm basically involves an E2 type elimination of HCI from the intermediate chlorosulfonium chloride salt with attack by chloride ion on the resultant carbonium-sulfonium ion.

The chlorination of sulfoxides has receibed a great deal of attention (19-30) since 1968 and this now includes stereochemical studies (24, 27) also. These have led Montanari's group to postulate that the intermediate oxochlorosulfonium chloride 9 undergoes simultaneous proton abstraction and chlorine atom migratio~l to furnish the cc-chlorosulfoxide.

Our own observations that cc-trichlorosulfoxides, such as 5, furnish sulfinyl chlorides and chlorocarbons upon chlorination in meth-

beeil.observed previously, the c lea~age reaction of the c/.-polychlorosulfoxide 5 had not been previously reported. We therefore examined it in some detail, by comparison of products fornied in three solvents of different polarities.

Chlorination of 5 in rnethylene chloride fi~rnished chloro~iiethanesulfinyl chloride, 6 (72)",), chloroform (53%), and carbon tetrachloride (11z). Direct cleavage of the oxo- chlorosulfoniurn chloride salt derived from 5 gives 6 and chloroforni. However, the presence of carbon tetrachloride as a product implicated the intermediacy of the tetrachlorosulfoxide 7 (see Scheme 3).'

Chlorination of the trichlorosulfoxide 5 in glacial acetic acid furnished chloromethane- suifinyl chloride (isolated as the sulfonyl chloride) and chloroform. N o carbon tetrachloride was formed indicating that direct

- 'An alterngive formulation in which trichloromethyl

carbanion (:CCl,) Is displaced by attack of CI- at sulfur in 7 is untenable in view of the product distribu- tion when 10 or 11 are chlorinated (oide infva).

410 CAN. J. CHEM [. VOL. 55, 1977

cleavage rather than Pummerer-type rearrangement is more favored in acetic acid than in the less polar methylene chloride.

By contrast, the results in [ I ] showed that chlorination of 5 in water permitted solvolysis to compete with cleavage by chloride ion.

see footnote 3

The isolation of carbon dioxide indicated that much of the cleavage occurred by nucleophilic attack of water on the most electrophilic carbon atom of the intermediate oxochlorosulfonium chloride salt. The nucleophilic competition observed when the chlorinations were carried out in aqueous media is the basis for treating the cleavage step as an ionic rather than free- radical reaction.

Chlorination of the tetrachlorosulfoxide 7 in water afforded chloromethanesulfonyl chloride 2 (68%), carbon tetrachloride (2073, and carbon dioxide (60z). Simple calculations per-

3Formic acid is readily oxidized to carbon dioxide under the reaction conditions.

mit the forn~ulation of a detailed pathway for the chlorination of 5 in water (see Scheme 4).

The reactions which involve sulfinyl chloride intermediates in aqueous medium are assumed to proceed through the sulfinic acids. However, in dry acetic acid, sulfinic acids cannot intervene. Amongst the mechanistic possibilities is the elimination of HCl from the intermediate oxodichlorosulfonium chloride salt 9 to furnish an intermediate analogous to sulfene ( 3 1). Should this have been the case, then chlorination of a sulfinyl chloride in acetic acid-d, would have furnished monodeuterated sulfonyl chloride. In fact, chlorination of methanesulfinyl chloride in acetic acid-d, furnished undeuterated methanesulfonyl chloride, thereby requiring acetolysis of the intermediate oxodichlorosulfonium chloride or, alternatively, the formation of a sulfinate- acetate mixed anhydride before reaction with molecular chlorine.

Hence, the complete pathway for the conversion of 1,3-dichloro-2-thiapropane, 3, into chloromethanesulfonyl chloride, 2, has been established and the cleavage step shown to occur on 1,1,3-trichloro-2-thiapropane-2-oxide, 5. I t seemed appropriate at this point to examine the structural requirements of the chlorosulfoxide substrates in general in terms of the cleavage step. I t will be shown In the ensuing sections how both a-chlorosulfides and -sulfoxides, or just simply dialkylsulfides, may be subjected to stepwise chlorination, oxidation, and cleavage steps, leading ultimately to sulfonyl chlorides, by a process which we propose is aptly named the 'sulfohaloform reaction'.

Chlorination of Methyl Sulfoxides In order to complement the work described

above on sl,u'-polychlorosulfoxides, I , l-dichloro-2-thiapropane-2-oxide, 10, was chlorinated in methylene chloride and the results in [2] were obtained.

C H , SO CI + CC14 + CHCI ,

(76%) ( 5 5 % ) (12%)

Since carbon tetrachloride was formed it is obvious that most of the cleavage reaction was occurring on the more highly chlorinated sulfoxide 11. Similar results were observed when either PO or 11 were chlorinated in glacial


5 C1, CICHz SO C1 + HC02H CKH, SO, C1 + C 0 2

F (27%) (37%)

CI, CICHz SO CI + CHCI, - CICH, SOz C1

(6%) (4%) CI,C SO CHzCl

7 (50%) C I \ ClCH2 SO Cl + C 0 2 A H,O CICHz S02Cl

(30%) (26%)

CI, CICH, SO C1 s CCI, A H 2 0 CICH, SO2 CI

(10%) ( 8%)

SLHEXIE 4

acetic acid: CH, .SO,.Cl CC1, AcCl

CI,CH,SO.CH, -+ 75% 76% 67%

Hence, when cleavage occurs via nucleophilic attack by chloride ion, it is necessary for the sulfoxide substrate to have at least three a- chlorine atonis, regardless of the substitution pattern. I t is interesting to note that the third chlorine atom 1s approximately equally effective in promoting smooth chlorinolysis of the sulfoxide (in methylene chloride or acetic acid) either when it is deployed to increase the electrophilicity of the carbon atom undergoing nucleophilic attack (e.g. 11) or when it is located in a position which enhances the electronegativity of the leaving group (e.g. 5).

Chlorination of 10, 11, and 7 in water furnished markedly different results, as follows :

CI,IH,O CH3.SOz CI 2 CCL, CO,

ClzCH SO CH, .--+ 70% 40% 22% 68% 10

CI,C SO CH, - 50% 24% 20% 56%

11

C1,C SO CHzCl - 0% 68% 20% 60%

7

The intermediacy of 11 in the chlorination of 10 and of 7 in the chlorination of 11 was established by isolating 11 and 7 from the chlorination. A straightforward analysis per-

mits the formulation of a detailed pathway for the reaction of 10 with chlorine in water (see Scheme 5). I t is now evident that, unlike the haloform reaction which requires a-trichloro substrates (ketones) for cleavage to occur in aqueous medium, the sulfohaloform reaction can take place with a-dichloro substrates (sulfoxides) in aqueous medium.

Chlorination of a-Chlorosu@des to Form Sulfonyl Clilorides

Since the isolation of the intermediate sulfoxides in the sulfohaloform reaction was ex- perimentally rather difficult we undertook an examination of the chlorination of a-chlorosulfides in aqueous medium in order to find evidence for the intermediacy of the a-chlorosulfoxides. The chlorination of 1,3-dichloro-2- thiapropane, 3, in water furnished the corresponding sulfone (4z) and chloromethanesulfonyl chloride 2 (70x1.

We have already established that chlorination of 3 proceeds primarily through the corresponding sulfoxide even in dilute aqueous medium. Thus the observation of low yields of the corresponding sulfone in this type of reaction can be taken to implicate the intermediacy of the sulfoxide since the sulfone must, of necessity, have been formed via the sulfoxide. Application of this criterion to I-chloro-2- thiapropane, 12, was successful in implicating the intermediacy of the corresponding sulfoxide also, since the sulfone was isolated in 1% yield.

These results along with those from 2-chloro-

CAN. J. CHEM. VOL. 5 5 , 1977

C1, CI, C12CH SO CH, HZO t CH, SO C1 HCO,H CH? SO2 C1 +CO: (60%) (60%)

10

CH, S O C1 + CO, b CH, SO, C1

(9%) H,O

(9%)

CI;C SO CH3

11 (16%) C1 CH; SO C1 T CCI, ---L H:O CH, SO, C1

I (1%) i 1%)

CI, ClCH2 SO C1 + CO, H:O CCIH, SO, C1

(3%) (3%)

CI,C S O CH,Cl

7 (6%) CI, CICH, S O Cl + CCI, H20 * CICH, SO, C1

i 1%) ( 1%)

3-thiapentane and 4-chloro-5-thianonane are tabulated in Table 2. The process is obviously a potentially useful sulfonyl chloride synthesis.

The overall results from the chlorination of chloromethyl phenyl sulfide in aqueous medium also showed the same behaviour, i.e. the formation of chloromethyl phenyl sulfone (2.5%) (along with benzenesulfonyl chloride (68%)) implicated the intermediacy of the chloromethyl sulfoxide. In contrast to the previous cases, the chlorination of chloromethyl phenyl sulfide took a long time to reach completion.

sulfinyl group of the intermediate oxochlorosulfonium chloride.

Thus far we had observed that cr-polychlo- rinated sulfoxides could be converted to sulfonyl chlorides without the formation of any sulfones. Chlorination of a-dichloro and simple a - chlorosulfoxides gave rise to minor amounts of sulfones. It appeared, however, that a potential barrier to extending this reaction to unchlorinated sulfides and sulfoxides might be the formation of substantial amounts of unchlorinated sulfones. This problem was solved as follows.

Furthermore, analysis of the partially chlorinated reaction mixture indicated that large Chlorination o f S~rlJides fo Form Sulfonyl

amounts of trichlorometl~yl phenyl sulfoxide Chlorides We began this portion of the work by ex-

were present before any significant amount of ploring reactions of some conveniently available

benzenesulfonyl chloride was formed. This result indicated that the phenyl ring virtually nullifies sulfoxides in order both to maximize sulfone

formation and to see if we could find reaction the electron-withdrawing effect of one chlorine

conditions which would suppress it. Such atom. Such an observation can be readily

chlorinations of DMSO were illuminating, rationalized via resonance forms in which the phenyl ring shares its n electrons with the giving the results in [3] and [4]. Similar results

H,O-HOAci 1 1) TABLE 2 Ylelds of sulfonyl chlorides prepared by [31 CH3 So CH3 *

shlorlnatlon of r-chlorosulfides In water CH, SO, C1 + C H 3 SO, CH, +CICHz SO2 CH,

(48%) ( 15%) (3%) Sulfide Sulfonyl chlor~de Yleld (%)

CICH2.S.CH2CI CICH2.SOz.Cl 70 CH3.S,CH2C1 CH3,SO,.CI 75 [4] CH, S O CH, t Clz

H,O +

Ph.S.CH2C1 Ph.S02.CI 67 CH3CH2.S.CHClCH3 CH3CH2.SOz.Cl 90 CH, SO2 C1 + CH, SO, CH, n-C4H9.SCHCl,n.C3H7 iz-C,H,.S02.CI 94 (26%) (70%)

GROSSERT AND LAWGLER 413

were obtained from the chlorination of di-n- propyl sulfoxide in water. Hence, sulfone formation was indeed a major potential complication to the useful formation of sulfonyl chlorides from unchlorinated sulfides and sulfoxides. This was not surprising since the results are consistent with those of Durst and Tin (32) and of Cinquini and co-workers (33), both of whom have observed sulfone formation via nucleophilic attack on oxochlorosulfonium cations.

However, after experimentation, it was found that chlorination of su@des in dilute aqueous acetic acid was s~~ccessful in concerting the su@des into sulfonyl chlorides, in high yield, without the interference of sulfone formation (see Table 3). By contrast, chlorination of the corresponding sulfoxides under the same conditions furnished significantly larger quantities of sulfones, implying that the reactlon pathway from the sulfides does not proceed through the corresponding sulfoxides but rather through the corresponding a-chlorosulfides, and hence through the E-chlorosulfoxides, etc.

Since the conditions had been established, which permitted direct chlorination of sulfides to sulfonyl chlorides by controlling the amount of water present in the solvent, one final mechanistic problem remained. In water, the cleavage step is primarily achieved with water functioning as the nucleophile. In dry acetic acid, chloride ion is the exclusive nucleophile. I t was not obvious just how competitive chloride ions would be zis-&cis water in dilute aqueous acetic acid, and in order to monitor this, we have chlorinated thiacyclopentane and isolated the a-chlorinated butanesulfonyl chlorides, as in [ 5 ] .

The formation of 13 was not unexpected, since chlorination of thiacyclopentane in glacial acetic acid permits its isolation in 28.64, yield as reported by Runge et al. (34). Since chloro-

TABLE 3. Yields of sulfonyl chlorides prepared from sulfides and sulfoxides by chlorination in dilute aqueous

acetic acid

Yield Sulfides/sulfoxide Sulfonyl chloride (%)

CH3CH2,S.CHZCH3 CH3CHZ.SO2.Cl 97 CH3(CH2),,S.(CHZ)3CH3 CH3(CH2)3.S02.CI 86 PhCH2.S,CH2Ph PhCH2.SOz.Cl 74 CH~(CH~)~ 'SO. (CHZ)ZCH~ CH3(CH2)2.S02.C1 76

sulfonium chloride salts are inert to acetolysis (35), the origin of this nionochlorosulfonyl chloride, under either conditions, is undoubtedly through direct chlorinolysis of thiacyclopenta~le to give 4-chlorobutane sulfenyl chloride. The driving force for this reaction is the release of ring strain and is parallel to the reactions of thiacyclobutane with chlorine in chloroform, or with sulfuryl chloride in pentane (36), which furnish 3-chloropropanesulfenyl chloride. There- fore the formation of 13 is not relevant to a consideration of the normal cleavage step in the sulfohaloform reaction.

However, Runge et a/. (34) did not report the formation of 4,4-dichlorobutanesulfonyl chloride, 14, upon chlorinating thiacyclopentane in glacial acetic acid. The sensitivity of Y-

chloro-chlorosulfonium chloride salts to hydrolysis, implicates the intermediacy of the a- chlorosulfoxide in the formation of 14. The absence of larger amounts of the o-dichloro- sulfonyl chloride, as well as the failure of any o - trichlorobutanesulfonyl chloride to form, indicate quite clearly that cleavage by chloride ions in dilute aqueous acetic acid is not an important or competitive process and therefore cleavage by the nucleophilic attack of water remains the major process in the cleavage step in dilute aqueous acetic acid.

The major pathways in the generalized sulfohaloform reaction have therefore been defined, and the overall reaction is outlined in Scheme 6.

SCHEME 6. The sulfohalofo~~m reaction

414 CAN. J . CHEM. VOL. 5 5 , 1977

Experimental General

Most experimental details have been described previously (37). Mass spectral samples were directly introduced using an all-glass probe and the spectra run at 40 eV with a source temperature of 15OCC. Elemental analyses were by Dr. F. Pascher (Bonn) or Galbraith Laboratories (Knoxville, Tenn.). Gas-liquid chro- matographic analyses were carried out with an N2 flow rate of 50 mllmin and the column temperature was 40 to 50 'C. Unless otherwise indicated, "washing an organic layer with NaOH" means that a 2 .5z w/v solution of NaOH was used to wash the organic layer, usually 100 ml aliquots, until the aqueous layer remained basic. "Standard work-up" of hydrophobic solvents implies that they were dried (MgSO,), filtered, and then rotary evaporated.

Chlorinations Chlorine flow rates were standardized by the use of a

calibrated rotameter. All chlorinations were maintained at 25-30-C by an ice-water bath. Unless otherwise stated, rates and reaction times are given in the form "232/50". This means a flow rate of 232 mllmin and a reaction time of 50 min. All times are given in minutes.

Yields It was often necessary to analyze reaction mixtures

quantitatively before work-up in order to avoid obtaining yields which reflected losses during work-up. None of the sulfur-containing con~pounds were detectable on glc. All sulfur compounds were observable in the nrnr and integration of the nrnr spectrum furnished satisfactory molar ratios. Carbon tetrachloride was detectable on glc and could be interrelated with the sulfur compounds by the addition of methylene chloride which appeared both in the glc trace and the nmr spectrum. The molar ratios, the total sample weight, and the following equa- tion permit the calculation of the weight of each component in any mixture.

where x, = mole fraction of 'i'th component, a ; = molecular weight of 'i'th component, K , ~ = weight (in grams) of the 'i'th component, T = total sample weight (in grams).

COz Deierminations Full details are provided elsewhere (37).

Chlorination of 1,3,5-Tvithiane 1,3,5-trithiane (17.11 g) was suspended in glacial

acetic acid (38 ml) and distilled water (8 ml) was added. The reaction became non-exothermic by the end of the chlorination (232140). The reaction mixture was diluted with ice water (25 ml), the organic phase separated, and the aqueous phase set aside.

The organic ohase was diluted with CHC1,4 (150 ml).

The aqueous phase was diluted to a volume of 150 ml with 95% ethanol, from 100 ml of which authenticated 2,4-dinitrophenylhydrazone of formaldehyde (2.03 g) was isolated (39). The results obtained after isolation and identification of the major products are given in Table 1 . Full details of identification methods are provided elsewhere (37).

Preparation of l,3-Dichloro-2-ihiapropcme, 3 1,3-Dichloro-2-thiapropane 3 was prepared from 1,3,5-

trithiane as described by Truce ei 01. (40). The distilled material from this reaction contains a persistent im- purity which showed an ir band at 1523 cm-'. The contaminant was completely removed when the dichlorosulfide was chromatographed on silica gel with CCI, using sulfide-silica gel ratios as low as 1 : 3. In a typical run 1,3,5-trithiane (300 g) furnished crude 1,3-dichloro-2- thiapropane (170 g). After column chromatography and redistillation, high purity dichlorosulfide 3 (121 g, 42.59,) was obtained.

Chlorinaiion of 3 in H20/HOAc 1,3-Dichloro-2-thiapropane 3 was dissolved in glacial

acetic acid (50 ml) and distilled water added. Following chlorination (232 ml/min), ice water (75 ml) was added and the resultant mixture extracted with CHCI, (4 x 100 ml). The combined CHC1, layers were washed first with NaOH then with distilled water. Standard work-up afforded products which were isolated by fractional distillation. 1,3-Dichloro-2-thiapropane-2-oxide, 4, had mp 36.5-37.5 "C; tlc (37) RF 0.48 (ether), after recrystallization from CCI,; ir (CHCI,) 1070 cm-' (vso); nrnr (CDCI,) F 4.57 (q, J = 11.0 Hz); ms ions at m/e 146 (M t), 11 1 and 49. The dichlorosulfoxide 4 was identical with authentic material (45) by nmr, ir, mp, and mixture mp. See Table 5 for details of products obtained.

Chlorination of l,3-Dichloro-2-thiapropane-2-oxide, 4 1,3-Dichloro-2-thiapropane-2-oxide 4 was chlorinated

as described in the previous experiment. The products were isolated by fractional distillation:

1,1,3-trichloro-2-thiapropane-2-oxide, 5, had bp 94 ^C/ 0.25 torr; R, 0.55 on tlc (4: 1 CHC1,-ether); ir (CHCl,) 1080cm-' (vs,); nrnr (CDC1,) 6 4.70 (s, 2H) and 6.60 (s, 1H); ms ions at m/e 180 ( M i ) 83, 49. Oxidation of 5 (40) furnished material identical to authentic trichlorosulfone by ir, nmr, and bp. Details of the products obtained are found in Table 6.

Preparation of Cl, CH,S.CN, Cl Details are provided elsewhere (37). The product was

identical to known material (40).

Preparation of l,l,3-Trichlovo-2-thiaprogane-2-oside, 5 1,1,3-Trichloro-2-thiapropane (24.56 g) was dissolved

in glacial acetic acid (100 ml), distilled water (4.4 ml) was added, and the mixture was chlorinated (232150). The reaction mixture was fractionated, furnishing 1,1,3- trichloro-2-thiapropane-2-oxide (19.6 g, 72.5%).

dried (M&.o,): filtered, and the CHCI, distilied off. Chlorination of 5 in H20-HOAc The residue was fractionated giving the results out- 1,1,3-Trichloro-2-thiapropane-2-oxide 5 (16.17 g) was

lined in Table 4. dissolved in glacial acetic acid (50 ml) and distilled water (4.4 ml) was added. Following chlorination (232/39),

4An additional run was carried out using ether as the ice water (75 ml) was added and the organic phase was solvent in order to check for the presence of chloro- separated. The aqueous phase was washed with CHCI, carbons. (100ml) which was combined with the organic phase.


TABLE 4. Fractionation of the products from the chlorination of 1,3,5-trithiane

Boiling point Fraction ('Cjtorr) Components Weight (g)

2 20-40125 C1CH20Ac 0.71 CICHZ.O.CH2CI

3 40-68120 CICHZ.S.CHzC1 5.31

4 70-80120 CICHZ.S.CHZC1 3.87 ClCHZ.S.S.CH,Cl Unidentified products

5 Cold trap in C1CH,.0.CH2CI 3.23 vacuum line CICHZOAC

CICH2.S.CHzCi

6 Solid deposited 1,3,5-trithiane 1 . 0 in fractionating column

*CAUTION: b~schloromethyl ether 1s a potent carcinogen (38).

TABLE 5. Products of the chlorination of 3 in H,O/HOAc

Weight Chlorination Volume (8) time (min) H 2 0 (ml) Products Yield (g)*

*Percentage yield in parentheses

Standard work-up gave a concentrate which was fractionated (glass-bead column, 67 torr), to give chloromethanesulfonyl chloride 2 (8.48 g, 64.0z) and a distillation residue of unreacted 5 (1.80 g, 11.2%).

Chlorination of5 in HOAc 1,1,3-Trichloro-2-thiapropane-2-oxide 5 (15.85 g) was

chlorinated (232130) in glacial acetic acid (50 ml). An nmr spectrum of the reaction mixture showed a molar ratio of 100: 73 : 27, CHCI,;'CICH,~SO~CI~CICH2~S02~C1 respectively. The reaction was chlorinated further with progress being monitored hourly. After 3.5 h the sulfinyl chloride - suifonyl chloride ratio was 3 : 7.

Ice water (75 ml) was added to the reaction mixture and the organic phase was removed. The aqueous phase was extracted with ether (l00m1) and the ether layer combined with the organic layer. The combined organic portion was diluted with ether to 200 ml and then divided into equal portions, A and B.

A. Portion A was dried (MgSO,) and concentrated. The bulk of the acetic acid was distilled off at 75 torr. Thc residue was dissolved in CHCI, (50 ml) and continuously extracted with water for 1 h. The aqueous phase was discarded and the extraction resumed with

fresh water for I h. Standard work-up of the CHCI, gave a residue which was fractionated at reduced pressure to yield chloromethanesulfony1 chloride 2 (3.90 g).

B. Quantitative glc and nmr integration established the yield of CHCI, to be equal to 759,. The ether solution was extracted with NaOH, washed with distilled water, dried (MgSO,), and fractionated, to furnish pure CHCI, identical with authentic material by bp, glc, and nmr.

Chlorination of 5 in CH2C12 1,1,3-Trichloro-2-th1apropane-2-oxide 5 (1 5.34 g) wab

chlorinated (232130) in CH,C12 (50 ml). Methylene chloride (10 ml) was dist~lled off and the presence of both CHCI, (53.2%) and CC1, (10.7%) was demonstrated (glc). The bulk of the chlorocarbons were distilled off and the residue rectified at reduced pressure affording chloromethanesulfinyl chloride 6 (8.14 g, 71.7Y,), bp 163.5 TI760 torr; ir (CHCI,) 1150 cm-' (vso); nrnr (CDCI,) 6 4.83 (5); ms nz/e 62, 49. Hydrolysis in distilled water, followed by chlorination in CH,C12, furnished chloromethanesulfonyl chloride 2 as expected.

Chlorination of 5 in H20 1,1,3-Trichloro-2-thiapropane-2-oxide 5 (1 1.32 g) was

CAN. J. CHEM. VOL. 5 5 . 1977

TABLE 6. Products of the chlorination of 1,3-dichloro-2-thiapropane-2-oxide, 4

Weight Chlorination Volume (g) time (min) H 2 0 (ml) Products Yield (g)*

*Percentage yield in parentheses

chlorinated (2321'105) in distilled water (50 ml). The organic phase was pipetted off and dried (CaCI,). Gas- liquid chronlatography established the presence of CHCI, (6.3%) and CC1, (10%). The organic phase was distilled at reduced pressure furnishing chloromethanesulfonyl chloride 2 (6.05 g, 64.5%).

In a separate experiment on 5 (1.155 g), the CO2 was isolated as BaC03 (0.802 g, 66.6%). Chlorination time was 50 min (1 16 mljmin).

Preparation qf 1-Chloro-2-thiopropane, 12 Details of this preparation are given elsewhere (36, 37).

Preparatiorz of CI, C.S. CH2 CI I-Chloro-2-thiapropane 12 (100 g) was chlorinated

(4481330) in CCI, (250 ml). The reaction mlxture was rectified furnishing 1,1,3-tetrachloro-2-thiapropane (181.9 g, 87.4%); bp 188 C/760 torr; nmr 6 5.00 (s) (CDCI,).

Preparation of 1,1,1,3-Tetrachloro-2-thiapropane-2-oxide, 7

Distilled water (12 ml) was added to 1,1,1,3-tetrachloro-2-thiapropane (31.19 g) in acetic acid (100 ml). After chlorination (232/50), the reaction mixture was fractionated to give 7 (16.8 g, 50%), bp 78 "C10.5 torr; R, 0.65 (CHCI,) which could be crystallized from 95% ethanol at OcC but melted upon returning to ambient temperature; ir (CHCl,) 1135 cm-' (vso); nmr (CDCI,) 6 4.57 (q, J = 1l.OHz); ms rnle 117, 82, 62, and 49. Anal. calcd. for C,H,CI,SO: C 11.13, H 0.93, 0 7.41; found: C 11.35, H 0.98. 0 7.38. Oxidation of 7 (40) yielded material identical to authentic tetrachlorosulfon~ by nmr, ir, and mixture mp.

Chlorination of 7 in H,O 1,1,1,3-Tetrachloro-2-thiapropane-2-oxide 7 (1 6.56 g)

was chlorinated (448/240) in distilled water (50ml). The organic phase was pipetted off and dried (CaCI,). Gas-liquid chromatography showed that CC1, (20%) had been formed. The residue was distilled furnishing chloron~ethanesulfonyl chloride 2 (7.80 g, 67.5%).

In a separate experiment (C1, : 232150) on 7 (1.030 g) C 0 2 was isolated as BaC0, (0.500 g, 60%).

Preparation of I,]-Dichloro-2-thiapropane-2-oxide, IOs DMSO (16.21 g) was chlorinated (232143) in glacial

acetic acid (50 ml) and distilled water (6.6 ml). The reaction was repeated on a second portion of DMSO (1 6.01 g). The combined reaction mixtures were diluted with water (150 ml) and extracted (CHCI,, 6 x 100 ml). The CHCI, was washed with NaOH then with distilled water (100 ml), dried (MgSO,), and evaporated. The residue was distilled at reduced pressure to yield 1,l-dichloro-2-thiapropane-2- oxide lo5 (17.53 g, 28.8%). Recrystallization (CCI,) of the distilled material afforded pure 10 as bundles of crystals (mp 32-33 'C); R, 0.49 (ether); ir (CHCI,) 1080cm-I (vSO); nmr (CDCI,) 6 3.75 (3H, s) and 6.42 (IH, s); ms rnje 146 (Mt ) , 83 and 63. Oxidation of 10 (40) yielded material identical to authentic dichloro-

- sulfone by nmr, ir, and mixture mp.

Chlorination of 10 in CH2 C12 l,l-Dichloro-2-thiapropane-2-oxide 10 (1 6.22 g) was

chlorinated (232125) in CH2CI (50 ml). A fraction was distilled at atmospheric pressure (44-75 "C). The residue was rectified at reduced pressure with a -75 "C cold trap in the vacuum line. The fraction from the atmospheric distillation plus the trap material contained CHCI, (1.5 g, 11.8%) and CCI, (8.8 g, 51.8%). The vacuum distillation furnished methanesulfinyl chloride (8.24 g, 76.3%); bp 136.5"C/760 torr; ir (CHCI,) 1140cm-' (vso); nmr (CDCI,) 6 3.37 (s); ms rille 98 (M?), 82, 63, and 48. Hydrolysis in distilled water, followed by chlorination in CH,C12 furnished methanesulfonyl chloride.

Chlorination of I0 in HOAc I ,1-Dichloro-2-thiapropane-2-oxide 10 (1 5.81 g) was

chlorinated (232130) in glacial acetic acid (50 ml). Acetyl

5CAUTION: this sulfoxide (Cl,CH.SO.CH,) is very unstable at room temperature and if stored in a tightly stoppered container may generate sufficient gas pressure to explode the container within 4 h. Proper storage for periods of 2 weeks (maximum) requires that the sample be stored in the dark using an explosion-proof container, at or below - 32 'C.

GROSSERT A LND LANGLER 417

chloride was established as being present in a 1 :I ratio with CCI, by nmr and glc. The reaction mixture was added to CH2Clz (100 ml) and ice water (100 ml). The organic phase was separated, dried (MgSO,), filtered, and the CHzC12 distilled off. A fraction (bp 44-75 "C) was collected at atmospheric pressure and the residue was distilled at 50 torr with a cold trap in the vacuum line. The atmospheric pressure fraction plus the trap material contained CCI, (1 1.10 g, 66.6%). The vacuum distillation afforded methanesulfonyl chloride (9.2 g, 7573.

Chlorination of 10 in H20 (a ) Partial Chlorination 1,l-Dichloro-2-thiapropane-2-oxide 10 (4.30 g) was

chlorinated (232128) in distilled water (25 ml). The reaction mixture was extracted with CHCI, (100 ml) which was washed with NaOH (50 ml aliquots), then with distilled water (50 ml), followed by a standard work-up. The residue was the trichlorosulfoxide 11 (0.54 g, 10.3%), as established by nmr, ir, and tlc.

(b ) E.uhaustive Chlorination 1,l-Dichloro-2-thiapropane-2-oxide 10 (1 6.18 g) was

chlorinated (232185) in distilled water (50 ml). The organic phase was pipetted off and dried over CaCI,. Gas-liquid chromatography established the presence of CCI, (2.4%), a sample of which was obtained by distillation at atmospheric pressure and was shown to be identical with authentic material by glc, ms, and bp.

Distillation of the residue at reduced pressure yielded methanesulfonyl chloride (8.84 g, 70.0%).

In a separate experiment on 10, (1.130 g; CI,: 232/50), CO, was isolated as BaCO, (1.067 g, 67.5%).

Preparation of l,l,I-Trichloro-2-thiapropane 1-Chloro-2-thiapropane (16.01 g) was chlorinated

(232135) in CH,CI, (50 ml). The reaction mixture was distilled, furnishing 1,1,1-trichloro-2-thiapropane (16.88 g, 61%); bp 148-149 'C; nmr (CDCI,), singlet at 6 2.75.

Preparation of l,l,l-Trichloro-2-tJiiapropane-2-oxid (11) 1,1,1 -Trichloro-2-thiapropane (1 6.36 g) was chlorinated

(232127) in glacial acetic acid (50 ml) and distilled water (6.6 n~l) . Water (75 ml) was added and the solution was extracted with CHCI, (4 x 100 ml), which was washed with NaOH, followed by distilled water. After standard work-up, the residue was distilled furnishing 11 (1 1.00 g, 61.7%) bp 86-88 "C/1.6 torr; crystals (from methanol) had mp 63-65 "C; R, 0.62 (4: 1 chloroform-ether); ir (CHCI,) 1100cm-' (vs,); nmr (CDCI,) 6 2.92 (s); ms mle 180 (Mt ) , 117, 82, 63, and 47. Anal. calcd. for C2H3CI3SO: C 13.24, H 1.67, O 8.82, S 17.67; found: C 13.26, H 1.56, 0 8.74, S 17.27. Oxidation of 11 (40), yielded material identical to authentic trichlorosulfone by nmr, ir, and mixture mp.

Chlorirlation of 11 in HOAc l,l,l-Trichloro-2-thiapropane-2-oxide 11 (16.83 g) was

chlorinated (232130) in glacial acetic acid (50 ml). Acetyl chloride was established as being present in a 1 : 1 ratio with CCI, by glc on the crude mixture. A small amount of acetyl chloride was distilled off and identified by ir, nmr, and glc. Work-up identical to that described

under "Chlorination of 10 in HOAc" afforded CCI, (9.95 g, 69.9%) and methanesulfonyl chloride (9.20 g, 86.1%).

Chlorination of 11 in Hz0 ( a ) Partial Chlorination l,l,l-Trichloro-2-thiapropane-2-oxide 11 (5.01 g) was

chlorinated (232130) in distilled water (25 ml). The organic phase was pipetted off and added to CHCI, (100 ml), which was washed with NaOH (50 ml aliquots) and then with water. After standard work-up, the residue was a mixture of unreacted 11 (0.75 g) and 1,1,1,3- tetrachloro-2-thiapropane-2-oxide 7 (1.06 g, 18.5%). The sulfoxide mixture was chromatographed on a column of silica gel (180 g). Elution with CHCI, (1 100 ml) furnished 7 and an additional litre of CHCI, furnished 11. The tetrachlorosulfoxide 7 was distilled and shown to be identical with authentic material by bp, nmr, ir, and tlc.

( b ) Exhaustice Chlorination 1,1,1-Trichloro-2-thiapropane-2-oxide 11 (16.04 g) was

chlorinated (4481185) in distilled water (50ml). The organic phase was pipetted off and dried over CaCI,. Gas-liquid chromatography established that CCI, had formed in 20% yield. The aqueous phase was extracted with CHCI, (2 x 100 ml) which was combined with the original organic phase. Standard work-up gave a residue which was fractionated at reduced pressure to furnish a mixture of methanesulfonyl chloride (5.08 g, 50%) and chloromethanesulfony1 chloride (3.16 g, 23.8%). Further distillation at atmospheric pressure gave four fractions, each of which was still a mixture. Fraction 1 (bp 161- 163 "C) contained ca. 15% chloromethanesulfonyl chloride and 85% methanesulfonyl chloride.

A portion of fraction 1 (212 mg) was added dropwise to a cooled (5 'C) solution of vanillin (21 1 mg) in pyridine (0,5ml). The ice water bath was removed and the solution was stirred at room temperature for 1 h. The reaction

mixture was diluted with CHCI, (50ml) which was extracted with 2.5% NaOH (50 ml), 2.5% HCI (50 ml), and distilled water (50 ml). Standard work-up gave a pale yellow oil (287 mg) which was dissolved in 95% ethanol (3 ml) and stored in the refrigerator overnight. Colorless crystals were filtered off and dried affording vanillin methanesulfonate (186 mg). After recrystallization, the sulfonate ester was shown to be identical to authentic material by tlc, ir, and mixture mp.

The concentrated mother liquor from the first crystallization was chromatographed on a preparative-layer plate (ether-CHCl,, 1 : 19). Methanol extraction of the upper band ( R F 0.55, detected by 250nm uv light) furnished a colorless oil (30.2 mg), which was identical to vanillin chloromethanesulfonate by tlc, nmr, and ir.

In a separate experiment on 11 (1.030g) carbon dioxide was isolated as BaC0, (0.928 g, 55.5%). Chlorina- tion time was 45 min.

Chlorination of 3 in H20 1,3-Dichloro-2-thiapropane 3 (16.41 g) was chlorinated

(4481200) in distilled water (50ml). Ice water (75 ml) was added and the reaction mixture extracted with CHCI, (2 x 100 ml). The residue from standard work-up of the CHCI, was distilled at reduced pressure yielding

418 CAN. J. CHEM.

chloromethanesulfonyl chloride (13.07 g, 70.4%). The distillation residue was covered with sufficient 10% NaOH to establish a p H z 7. The solution was acidified (concentrated HCI) and poured into CHCI, (200 ml). Stan- dard work-up gave 1,3-dichloro-2,2-dioxide (790 mg, 3.8%); after recrystallization (95% ethanol), this was shown to be identical with authentic dichlorosulfone by nmr, ir, mp, and mixture mp.

Chlorination of 12 in H20 I-Chloro-2-thiapropane 12 (15.76 g) was chlorinated

(448198) in distilled water (50 ml) similarly to the chlorination of 3. Products were methanesulfonyl chloride (14.10 g, 75.4%) and 1-chloro-2-thiapropane-2,2-dioxide (193 mg, 1.2%). Details are provided elsewhere (37).

Cl~loririarion of Ph.S,CH2Cl in H20 Chloromethyl phenyl sulfide (16.01 g) was chlorinated

(4481130) in distilled water (50 ml). By the end of this time all of the organic material had crystallized from solution and all reaction had ceased. The reaction mixture was extracted with CHC1, (2 x 100ml), followed by standard work-up. Analytical tlc (CHC1, eluant) showed a spot at RF 0.49 (assumed to be C12CH.S0.Ph), a spot at RF 0.70 (identical to CI,C.SO,Ph), and a spot at R, 0.81 (identical to Ph.S02.CI). The bulk of the material was Cl3C.SO.Ph and an ir of the crude showed the expected band at 1100 cm-I (vso). The crude product was dissolved in acetic acid - H 2 0 , 1 : 1, (50 ml) and chlorination (4481130) was repeated. Repetition of the work-up outlined above furnished crude product which showed about a 1 : 1 mixture of CI,C.SO,Ph to Ph.SO2.C1 on tlc and the complete absence of the product previously observed at R, 0.49. This new crude product was further chlorinated (4481130) in glacial acetic acid (15 ml) and distilled water (25 ml). The reaction mixture was extracted with CHCI, (4 x 100ml) which was dried (MgSO,) and rotary evaporated. Analytical tlc (37) showed the absence of CI,C.SO.Ph. The residue was fractionated at reduced pressure providing benzenesulfonyl chloride (12.04 g, 67.3%), identical to authentic material by tlc, nmr, ir, and bp. The distillation residue contained Ph.S02.CH2.C1 (500 mg, 2.5%). Two preparative-layer plates were spotted with residue (100 mgl plate) and eluted with CHCI,. Methanol extraction of the bands at RF 0.70 furnished chloromethyl phenyl sulfone identical with authentic material by nmr, ir, and tlc.

Preparation of P/L.SO.CC~, Trichloromethyl phenyl sulfide (16.20 g) was chlori-

nated (232127) in glacial acetic acid (50 ml) and distilled water (6.6 ml). The reaction was rerun on more Ph.SO.C- CI3 (15.96 g). The combined reaction mixtures were diluted with water (100ml) and extracted with CHCI, (4 x 100ml) which was washed with 5% NaOH and then with distilled water. Standard work-up gave a residue which contained unreacted sulfide (10.44 g) and Ph.SO.CCI3 (20.19 g, 58.9%).

Some crude material (26.33 g) was chromatographed on silica gel (1560 g). Elution with CC1, (6 1) furnished trichloromethyl phenyl sulfide (8.86 g). Further elution with diethyl ether (5.2 1) yielded trichloroniethyl phenyl sulfoxide (17.35 g). Recrystallization (95x ethanol) to give colorless needles; mp 77-78 ' C ; RF 0.61 (CHCl,); ir (CHCI,) 1100cn1-' (vso); nmr 6 7.75 (m); ms mie

242 (Mt) , 125, 117, 109, 77, and 51. Anal. calcd. for C,H,CI,OS: C 34.52, H 2.07, C1 43.7; found: C 34.79, H 2.28, C1 42.9. Oxidation of the sulfoxide (40) gave sulfone identical to that obtained by oxidation of the sulfide by tlc, nmr, ir, and mixture mp.

Chlorination of CH3CH2.S.CHC1CH3 in H z 0 2-Chloro-3-thiapentanc (16.77 g) was chlorinated

(448/104) in distilled water (50 ml). The reaction mixture was partitioned between ice water (75 ml) and CH2C12 (10 ml). The aqueous phase was extracted with CH2CI, (100 ml). Standard work-up of the combined CH2C12 layers gave a residue which was rectified at reduced pressure giving ethanesulfonyl chloride (15.54 g, 89.6%) bp 90-92 "C/55 torr.

Chlorination of n-C4H,,S.CHCl.CH2CH2CH3 in H20 4-Chloro-5-thianonane (15.95 g) was chlorinated (448,

100) in distilled water (50 ml). The reaction mixture was extracted with CHCI, (2 x 100 ml) which was dried (MgS04), and evaporated. The residue was fractionated at reduced pressure furnishing 1-butanesulfonyl chloride (13.0 g, 94.3%).

Ci~lorit~ation of DMSO in I : I H20-HOAc DMSO (15.91 g) was chlorinated (4481110) in glacial

acetic acid (25 ml) and distilled water (25 ml). Products were methanesulfonyl chloride (1 1.30 g, 48%), dimethyl sulfone (2.78 g, 14.7%), and 1-chloro-2-thiapropane-2,2- dioxide (0.75 g, 2.9%). Details are provided elsewhere (37).

Chlorination of DMSO in H z 0 DMSO (16.11 g) was chlorinated (448197) in distilled

water. Total dimethyl sulfone isolated was 13.64 g (70.3%) and total methanesulfonyl chloride isolated was 6.23 g (26.2%). Details are provided elsewhere (37).

Clzlorination of (n-C3H7)2S0 in H20 Di-n-propyl sulfoxide (15.79 g) was chlorinated (448/

105) in distilled water (50 ml). Ice water (75 ml) was added and the mixture was extracted with CHCI, (2 x 100 ml). Standard work-up gave a residue which was fractionated at reduced pressure to yield l-propanesulfonyl chloride (6.71 g, 39.8%); bp 104-106 "C/65 torr, and di-n-propyl sulfone (5.65 g, 31.3%); bp 88 "Ci0.1 torr.

Preparation of Sulfonyl Chlorides from the Coriesporiding Symmetric Sulfide or Sulfoxide

The substrate was dissolved in glacial acetic acid (50 ml) and the appropriate quantity of distilled water was added. Chlorine (448 m1,'min) was bubbled through the solution. Chlorination was interrupted as necessary to maintain the reaction at room temperature. Ice water (75 ml) was added to the reaction mixture which was then extracted with CHCI, (4 x 100ml). The CHCI, layers were washed with 2.5% ww,v NaOH (3 x 100 1111) and subjected to standard work-up.

Diethyl sulfide (16.01 g, 7.5 ml H,O, 108 min chlorination) gave a residue which was fractionated at reduced pressure to yield ethanesulfonyl chloride (22.12 g, 96.6%).

Di-n-propyl sulfoxide (16.00 g, 6.6 ml K 2 0 , 90 min chlorination) gave a residue which was fractionated at reduced pressure to yield di-n-propyl sulfone (1.50 g,

GROSSERT AND LANGLER 419

8.4%) and 1-propanesulfon~l chloride (12.94 g, 75.6%). postgraduate fellowship to one of us (R.F.L.) Di-n-butyl sulfide (16.00 g, 6.6 ml H 2 0 , 126 min is gratefully acknowledged.

chlorination) gave a residue which was rectified at reduced pressure to furnish 1-butanesulfanyl chloride (14.74 g, 86.2%). 1. J . S. GROSSERT and R. F. LANGLER. J. Cheni. Soc.

Dibenzyl sulfide (16.01 g, 6.6 ml H 2 0 , 75 min chlo- Chem. Commun. 49 (1973). rination) gave a residue which was crystallized from 2. S. W. LEE and G. DOUGHERTY. J . Org. Chem. 5. 81 benzene - low-boiling petroleum ether to yield phenyl- (1940). methanesulfonyl chloride (8.82 g). The mother liquor 3. A, G. K o s r s o v ~ . Acta Univ. Voroneg. 8. 92 (1935); furnished another 1.71 g to give a total yield of 73.3%. Chem. Abstr. 32.6618 (1938).

4. 1. B. DOLGLASS, V. G. SIMPSON, and A. K . SAWYER. Chlovir2ation of Thiacyclopentane in HOAc-Hz0 J . Org. Chem. 14, 272 (1949).

Thiacyclopentane (15.97 g) waschlorinated(4481106) in 5, F, WUDL, D, A , LIGHTYER, and D. J , CRAM, J , Am, glacial acetic acid (50 ml) and distilled water (7.5 ml). Ice 89. 4099 (1967), water (75 ml) was added and the mixture was extracted 6, W, E, LAWSON and T , P, DAWSON, J , Am, Chem, with CHCI, (4 x 100 ml). The CHCI, was washed with

Sot, 49, 3119(1927), 2.5%w/v NaOH(3 x 100 nll)anddistilledwater(100ml), 7, K , and W, VoGT, J~~~~~ ~ i ~ b i ~ ~ them. dried (MgSO,), and rotary evaporated. The residue was 381, 337 (1911). fractionated at reduced pressure to yield a mixture of 8, T , ZINCKE and W, FROHNEBERG, pr, nt sch , them, sulfonyl chlorides. The mixture contained C1(CH,),S02- Ges. 43. 837 (1910). C1 13 (3.10 g, 8.9%) and CI,CH(CH2)3SOzC114 (1.83 g, 9, T , Z I ~ C K E and W . RUPPERSBERG. Ber. ntsch. Chem. 4.573. A sample (2.01 g) of the distillate was chroma- Geb. 48, 120 (1915). tographed on a silica gel column (200 g). Elution with 10, T , zlNcKE and W, FROHNEBERG, B ~ ~ , ~ t ~ ~ h , Chem, CHCI, (650 ml) furnished a clean mixture of 13 and 14 Ges. 42,2721 (1909). ( 2 : 1). A second column run on 1.99 g of distillate 11, H, KWART L, J , M ~ ~ ~ ~ ~ . J, A ~ , Chem, sot, 80, furnished additional 2: 1 mixture. The total chroma- 884 (1958). tographed mixture from chromatography weighed 1.78 g. 12, W, G , p H l ~ ~ 1 ~ s and K . W. R ~ r r s . J . Org. Chem. 36. Strong bands at 1350 and 1162 cm-' were virtually 3145 (1971). the only bands present in the ir of the 2: 1 mixture. 13. G. E. W r ~ s o ~ , JR. and M. G. HUANG. J . Org. Chem.

A portion of the chromatographed mixture (1.01 g) 35, 3002(1970), was added drop-wise to a "Id solution of phenol 14, G. E. WILSON, JR. and R. ALBERT. J . Org. Chem. 38. (419 mg) in pyridine (3 ml) and the reaction mixture 2160(1973), was stirred at room temperature for 1 h. Chloroform 15, H , KWART andR. K . MILLER. J . Am. Chem. Soc. 78. (100 ml) was added and the solution washed with 2.5% 5008 (1956). N a 0 H (50 ml), 2.5% HCl (50 ml), and distilled water 16, H, KWART and R. W. BODY. J. Org. Chem. 30. 1188 (50 ml). The CHC1, was dried (MgS04), and rotary (1965). evaporated to yield a crude phenate mixture (938 mg), 17, H, KW,\RT. R , W, B ~ ~ ~ , alld D, M , H o F ~ ~ ~ ~ , crystallization of which (95% ethanol) afforded three Chem. Commun. 765 (1967). crops. Crops 1 and 2 (150 mg) were mixtures of ~henates . 18, H . KWART and P. S. STRILKO. Chem. Commun. 767 Crop 3 (130 mg) was pure C12CH(CH2)3S020Ph. The (1967). mother liquor from the third crystallization afforded 19, R , N , L~~~~~~ and D, C, K , cHANG, ~ ~ t ~ ~ h ~ d ~ ~ ~ residual phenate mixture (560 mg). Lett. 5415 (1968).

The (560mg) was chromatographed On five 20, G. T~UCHIHASHI and S. IRIUCHIJIMA. Bull. Chem. preparative tlc plates with benzene elution (2 x ). Each Sot, Jpn, 43. 2271 (1970), plate had five bands visible under uv light, i.e., RF 0.97, M , CINQUINI, S, coLONNA. and F, M ~ ~ ~ ~ ~ ~ ~ ~ . J , 0.91, 0.83, 0.77, 0.68. Chem. Soc. D, 607 (1969).

he band at R, 0.77 gave C1(CH2),S02OPh (251 mg) 22, S, I R ~ ~ C H ~ J ~ M A and G. TSUCHIHASHI. Tetrahedron as a colorless oil. Lett. 5259 (1969).

The band at R~ 0.83 gave C12CH(CH2)3S020Ph 23, M . CINQUINI and S. COLOKNA. J . Chem. Soc. Perkin (138mg) as fine needles from 95% ethanol, mp 60- Trans. 1, 1883 (1972). 61.5 'c; (CHCI,) 1375 and 1140 cm-' ( ~ ~ 0 2 ) ; nmr 2.25

24. M, CINQUINI, S. COLONNA, R. FORNASIER, and F. (4H, t), 3.34 (2H, t), 5.83 ( lH, t), and 7.34 (5H, s); MONTANARI. J . Chem. Soc. Perkin Trans. 1. 1886 ms m/e 125,94,65 and 53. Anal. calcd. for C, ,H, 2C1203S: (1972). 42.427 4.27, C1 25.04, O 16.95, 11.32; found: 25, M. CINQUINI, S. COLONNA, and D. IAROSSI. Boll. Sci. C 42.80, H 3.94, CI 24.84, 0 17.04, S 11.19. Fac. Chim. Ind. Bologna, 27, 197 (1969).

The remaining three bands gave minor quantities and 26, M, CINQUINI. S, COLoNNA, and D, LANDINI , J , were discarded. Chem. Soc. Perkin Trans. 2,296 (1972).

27. P. CALZAVARA, M. CINQUINI. S. COLONNA, R. FOR- NASIER, and F. MONTANARI. J . Am. Chem. Soc. 95.

Acknowledgements 7431 (1973). 28. J . K L E ~ N and H. STOLLAR. J . Am. Chem. Soc. 95,

We thank Dalhousie University and the 7437 (1973). National Research Council of Canada for 29. 6, TSUCHIHASHI and K . OGURA. ~ ~ 1 1 . Chenl. sot. financial support. The award of an NRCC Jpn. 44. 1726 (1971).

420 CAN. J. CNEM. VOL. 5 5 , 1977

30. K.-C, TIN and T. DURST. Tetrahedron Lett. 4643 (1970).

31. J . F . KING. ACC. Chem. Res. 8 , 10 (1973, and refer- ences therein.

32. T . DURST and K.-C. T IN. Can. J . Chem. 49, 2374 (1971).

33. R . ANNUNZIATA, M. CINQUINI, and S . COLONNA. J . Chem. Soc. Perkin Trans. 1,2057 (1972).

34. F. RUNGE, E. PROFFET, and R. DRUZ. J . Prakt. Chen~. 2,279 (1955).

35. J . S. GROSSERT, W. R . HARDSTAFF, and R. F. LANG- LER. J . Chem. Soc. Chem. Commun. 50 (1973).

36. F. G. BORDWELL and B. M. PITT. J . Am. Chem. Soc. 77,572 (1955).

37. G . K. CHIP and J. S. GROSSERT. Can. J . Chem. 50. 1233 (1972); J. S . GROSSERT and R. F. LAKGLER. J .

Chromatogr. 97, 83 (1974); R. F. LANGLER. Ph.D. Thesis, Dalhousie University. 1975.

38. Org. React. 19.422 (1972). 39. R. L. SHRINER. R. C. FUSON, and D. Y . CURTIN. The

systematic identification of organic compounds. 5th ed. Wiley. New York. 1964. p . 126.

40. W. E. TRUCE. G. H. BIRUM, and E. T. MCBEE. J . Am. Chem. Soc. 74,3594 (1952).

41. H. E. FRENCH and R. ADAMS. J . Am. Chem. Soc. 43. 651 (1921).

42. P. M. G . BAVIN. Can. J . Chem. 42.704 (1964). 43. F. S. H. HEAD. J . Chem. Soc. 2972 (1963). 44. S. R . Buc. U.S. Patent No. 2704299 (1955): Chem.

Abstr. 50. 1891c (1956). 45. F. 6 . MANN and W. J . POPE. J . Chem. Soc. Trans.

123, 1172 (1923).

Sulfides as precursors for sulfonyl chloride synthesis

RICHARD FRANCIS LANGLER,' ZOPITO ALESSIO MARIKI. AND EDWARD SOLIMERS PALD DING Cher?li.~frx Drprri.ttrzo~r, Dalholrsie Ut~i~.er..sir~, Hnl$o.~, .V.S., Car~n~lcr B3H4.33

Received April 16. 1979

RICHARD FRANCIS LANGLER, ZOPITO ALESSIO MARIKI, and EDWARD SOMMERS SPALDING. Can. J. Chem. 57,3193 (1979).

Sulfides are advanced as sulfonyl chloride precursors. SN2 cleavage of the intermediate sulfonium ions is discussed in conjunction with both the sulfohaloform pathway and our previous hypothesis that asymmetric chlorosulfoniuni chloride salts undergo Purnmerer rearrangements which exhibit regioselectivity that can be anticipated on the basis of substituent electronegativity difference (AX,). Thioglycolic acid is developed as a new sulfur transfer agent for sulfonyl chloride synthesis.

RICHARD FRANCIS LANGLER, ZOPITO ALESSIO MARINI et EDWARD SOMMERS SPALDING. Can. J. Chem, 57.3193 (1979).

On propose les sulfures colnme prCcu~.seurs des chlorures de sulfonyles. On discute du clivage des ions sulfoniums intermediaires selon un mCcanisnie S,2 conjointement avec le cheminenient du sulfohaloforme et de notre hypothkse anterieure. Cette derniere stipule que les chlorhydrates de chlorosulfonium asymetriques subissent des transpositions de Pummerer qui niontrent une rCgiosClectivitC et qui peuvent &ire prCvus & partir de la difference d'ClectronCgativite des substituants (AX,). On a rnis en evidence I'acide thioglycolique comme un nouvel agent de transfert de soufre dans la synthkse du chlorure de sulfonyle.


Imtroduetion The conversion of sulfides into sulfonyl chlorides

Our previous studies of the chlorinolysis of sulfur requires a cleavage step in the chlorinolysis reaction. compounds (1-8) have been directed toward the These reactions proceed, in general, by chlorosul- development of new synthetic methods for the pre- fonium cation intermediacy so that cleavage2 may

paration of sulfonyl chlorides (2, 4, 5). Sulfonyl Occur in either Or S ~ 2 fashion as shown in chlorides can furnish a variety of functionalities Scheme 1. We have previously reported the applica- (9-17) and may be prepared with well established tion of benzylic sulfides to the synthesis of sulfonyl methods (2, 9, 18, 19). A widely employed approach chlorides (5). We believe that the cleavage step in involves the aqueous chlorinolysis of sulfur-con- these an mechanism. tainirlg substrates viz. sulfenyl chlorides (20, 211, Extensions of the approach which utilizes sulfides mercaptans, disulfides, thiolesters, B~~~~ salts (221, in which one substituent attached to sulfur will form isothioureas (23), thiocyanates (24), sulfinyl chlorides a carbocation during chlorinolysis are readily en- (25), thiolsulfonates (26), and sulfinic acids (2, 27). visioned. In particular, in cases where the desired

We have beell developing the aqueous chlorinolysis sulfonyl chloride requires a carbon substituent which

of sulfides as an approach to the preparatioll of would itself form a stable carbocation, one would

sulfonyl chlorides (4, 5, 7). choose a sulfide in which the group to be lost would

excellent review of methods for the pre- give rise to a carbocation of superior stability to that paration of sulfides has recently become available ex~ec tedfor the group to be retained. unfortunately, (28). The most general approach to sulfide synthesis extensions of this approach have very little utility involves llucleophijic substitutioll by mercaptide since sulfonyl chlorides in which the carbon sub-

anions on carbon bearing a suitable leaving group, stituent can form a particularly stable carbocation This reaction has been extended to include simple are themselves unstable%nd cannot be prepared (12, aromatic substrates with a leaving group attached 15, 30); e.g., aqueous chlorinolysis of 1-naphthyl- directly to a phenyl ring (29). A simple general methyl mercaptan affords I-chloromethyl naphtha- scheme for sulfonyl chloride synthesis is shown in lene and not the expected sulfonyl chloride (15). eq. [I 1. - The detailed pathway by which alkyl sulfides are

g Cl,/H,O %vidence that these reactions are ionic and not free radical [ I ] R'SH + X-R" +R'SR" -R"S02CI has been presented previously (4).

HOAc 3We have suggested that the mode of decomposition is a 'Enquiries should be directed to Dr. R. F . Langler, unimolecular ionic process (15) whereas Kice has suggested a

Chemistry Department, Mount Allison University, Sackville, radical mechanism (12) or a cyclic transition state formed by N.B., Canada EOA 3C0. attack of chlorine on the ci carbon as it leaves from sulfur.

0008-40421791243 193-07$0 1 .OO/O 9 1979 National Research Council of CanadaIConseil national de recherches du Canada

CAN J . CHEbI. VOL 57. 1979

/ X = 0 or lone pair \

HOAc

transformed into sulfonyl chlorides without the intermediacy of carbocations in the cleavage step (the sulfohaloform reaction) has been reported recently (4). (See Scheme 2.)

+ R , SO. CC12R' - R , SO. CHCIR'

R.SO.C1 R.S02.C1

\ R,SO.OH ,-'

SCHEME 2. The sulfohaloform reaction

The cleavage step in the sulfohaloform reaction appears to proceed by an S,2 mechanism (4). Several recognized complications may arise which interfere with the cleavage step: (i) steric crowding may preclude the existence of the desired p r ~ d u c t , ~ (ii) steric crowding in the intermediate a-polychloro- oxochlorosulfonium chloride can shift preferred nucleophilic attack by H,O (4) to chloride ions with a consequent reduction in overall reaction rate and some concomitant shift in the electrophilic site at- tacked (la), and (iii) carbocation formation prior to formation of the requisite a-polychlorosulfoxide intermediate can give rise to a sulfonyl chloride in which the carbon a to the sulfonyl group bears chlorine atoms (6).

Application of the sulfohaloform pathway to the

4Reference 31 gives a possible example.

analysis of asymmetric sulfide chlorinations requires that one be able to predict which of the first formed a-chlorosulfides will predominate. The substituent which incorporates the first chlorine atom is the one which will be ultimately cleaved. We have previously (la) reported that asymmetric sulfide chlorinations in aprotic media introduce chlorine more readily on the a-carbon bearing the nlore electronegative substituent. If this postulate holds in protic media, the major sulfonyl chloride formed will be the one which retains the sulfide substituent having the a- carbon atom with the less electronegative group(s). Mercaptans could then be assessed as sulfur transfer agents for sulfonyl chloride synthesis by choosing R' (in eq. [I]) so that Xp(Rt) > XP(R1').

TABLE 1 . Group electronegativities*

Group

H- CH3- CH3CH2- CICHZ- PhCH,- CH30C(O)CH2- K02C- CI-I3(CH2)2 CH3tCH213- CH3iCHz)4- CHS(CHZ)S- CH~SOZ(CHZ)~- PhS0z(CH2)2-

Pauling electronegativity

(X,) a b

*Group electronegati~ities without a and b values are taken from Huheey's data (32, 33). Group electronegativities uhere a and b Palues are supplied were calculated using Huheey's method.

LANGLER E T AL

TABLE 2. Exhaustive chlorinations of asymmetric sulfides in aqueous acetic acid

Sulfonyl chlorides Sulfide substrates Ax, (RICH~SCHZRZ) Major (2 yield) Minor (2 yield) ( X R , - XR,)

'Exhaustive chlorinations of last 3 cases mere reported pre

Results and Discussion In order to test these proposals, a simple series of

sulfides was subjected to exhaustive chlorination in aqueous acetic acid. The appropriate substituent electronegativities are shown in Table 1. Results of the chlorinations with appropriate AX, values are presented in Table 2. These results are consistent with the outcomes expected on the basis of AX, and sulfohaloform reaction arguments as presented above.

Inspection of the substituent electronegativities tabulated by Huheey (32, 33) led to the conclusion that thioglycolic acid would be an excellent sulfur transfer agent for sulfonyl chloride synthesis as depicted in eq. [I]. We have prepared a series of sulfides from a variety of halides and thioglycolic acid as shown in eq. [ 2 ] .

C H 3 0 H (21 R-X + HSCH2C02H RSCH2COzH

CH,ONa 1

The first problem is that of delineating the pathway by which the sulfide acids 1 are transformed into sulfonyl chlorides upon exhaustive chlorination in aqueous acetic acid. The pathway study was carried out on the sulfide acid l a (R = CH,).

Chlorinolysis of l a in aqueous acetic acid for a short time furnished 1,1,1-trichloro-2-thiapropane- 2-oxide (2) in 75% yield. Since we have previously established (4) that 1,I-dichloro-2-thiapropane-2- oxide reacts5 under these conditions to furnish methanesulfonyl chloride in 60% yield without proceeding through the trichlorosulfoxide, it follows that the dichlorodimethyl sulfoxide is not the principal intermediate giving rise to 2. Furthermore, we have shown (la, 4) that sulfides with strongly electron-withdrawing groups on a carbon a to the sulfur atom furnish chlorosulfonium chloride salts

5The dichlorosulfoxide is converted to the trichlorosulfoxide in 16% yield under these conditions (4).

viously (4)

which hydrolyze to furnish the corresponding sulfoxides rather than Pummerer rearranging to the corresponding a-chlorosulfides. Therefore the sulfide acid l a must react as shown in Scheme 3. Details for the mechanisms have been given previously (la, 3, 4).

The pathway elaborated for the transformation of the sulfide acid la into a sulfonyl chloride mixture presents a problem. Namely, there is no Pulnmerer rearrangement of a chlorosulfoniuin chloride salt anywhere in the pathway. Since the first step very likely produces a sulfoxide, all Pummerer rearrangements are occurring from oxochlorosulfonium chloride salts. In order that substituent electronegativity be a useful basis for evaluating mercaptans as sulfur transfer agents vis-8-vis sulfonyl chloride synthesis, sulfoxide chlorinations must also exhibit regioselectivity which correlates with substituent electronegativity difference (AX,). Table 3 presents the asymmetric sulfoxide chlorinations which are presently known. The data in Table 3 suggest that AX, may very well continue as a useful basis for

CIz/H,O CH, . S .CH2C02H CH3. SO. CHzCO2H

l a HOAc

I C

CH3. SO. CC12COzH 4------ CH?. SO. CHCICOzH

CH,. SO. CCI, + CO, - CICH, . SO. CCI, 2

1

CH, . SO. C1+ CCI, + C 0 2 CICH,. SO. C1+ CCI, + C 0 2

TABLE 3. Regioiso~neric chlorosulfoxides from sulfoxide chlorinations

Sulfoxide substrate (R,CH,SOCH,R,)

Chlorosulfoxide products AX, (% yield) (XR, - XR,) Reference

*There has been a report that benzyi methyl sulfoxide chlorinates with l~ t t l e o r no reg~oselecti\,ity \\hen iodobenzene dichloride is em. ployed as the chlorinating agent (35).

TABLE 4. Yields* of sulfonyl chlorides obtained via sulfide acids 1

Substrate Product Overall yield (2)

CH3CH2Br CH,CH,SO,CI 70 CH3(CH2)2Br CH3(CH2),S0,C1 65 CH3(CH,)3CI CH3(CH2),S0,CI 60 CH3(CH2I45r CH3(CH,),SO2CI 80 CH3(CH2I5Br CH3(CH2)5S02CI 78 CH3S0,(CH2)3CI CH3S02(CH2)3S02CI (3n) 50 PhS02(CH2)3CI PhS02(CH2)3S02CI (30) 60

*Yields are reported for si~lfonyl chlorides after p i

assessing mercaptans as sulfur transfer agents whether chlorinolyses of the sulfide intermediates follow the sulfohaloform pathway or the closely related pathway shown in Scheme 3.

We have chlorinated a series of sulfide acids B which furnished the expected sulfonyl chlorides in good yields as shown in Table 4. The sulfonyl chlorides 3a and 3b were prepared as examples of more interesting substrates which can be accessed with this new method. The complete route for the preparation of their precursors 7a and 7b appears in Scheme 4.

All of the substrates examined for the development of both the present method and our previously published method (5) for the synthesis of sulfonyl

pyridine RSH + CHZ=CHCOZCH, ------+ RSCH,CH2C02CH3

40 R = CH,- 40 R = Ph-

SOCI, RSCH2CH,CH,CI - RSCH,CH,CH,OH

CHCI, 6u R = CH2- 5a R = CH,- 6b R = Ph- 5b R = Ph-

I Cr0,IHOAc

R . SO2. CH,CH,CH2CI 7<1 R = CHs- 7 b R = Ph-

irification by distillation or recrystallization

chlorides have substituents attached to sulfur via primary carbon atoms. Consequently we have examined a secondary system in order to compare the two methods. The results are shown in eqs. [3] and [4].

Clz/H20 [3] (CH3)2CHSCH2C02H - (CH3),CHOAc

10 HOAc 46%

+ (CH,),CHSO,CI + CI,CHS02C1 54% 46%

CIZ/H20 [4] (CH3)2CHSCH2Ph (CH3)2CHS02CI

HOAc + PhCH2C1

The results shown in eq. 131 indicate that chlorinolyses of the sulfide acids 1 are subject to complication by S,1 dissociation prior to formation of the a- polychlorosulfoxide intermediates necessary to obtain S,2 cleavage. However, as shown in eq. [4], benzylic sulfides are not susceptiblc to such a complication since S,1 cleavage of the benzyl group occurs very early in the reaction pathway (5). The pathway for the chlorinolysis of Ib appears in Scheme 5.

We have now successfully developed two sulfur transfer agents for sulfonyl chloride synthesis i.e. phenylmethanethiol (5) and thioglycolic acid. While yields are generally higher and reaction times shorter for chlorinolvses of benzylic sulfides. there is a drawback in thei; apglication;o the synthesis of smaller sulfonyl chlorides. When benzylic sulfides are exhaustively chlorinated in aqueous media the

sulfonyl chloride product is contaminated with approximately one equivalent of benzyl chloride and a small amount of benzyl acetate (5) . When the desired sulfonyl chloride has a volatility comparable to that of benzyl chloride, purification is tedious and time consuming. In contrast, the chlorinolysis of sulfide acids 1 produces the desired sulfonyl chlorides carbon dioxide and carbon tetrachloride and the sulfonyl chlorides are therefore isolated in good purity directly from the reaction mixtures. Thus thioglycolic acid is a superior sulfur transfer agent for the preparation of small sulfonyl chlorides where the carbon bearing the chlorosulfonyl group in the product will not be a suitable carbocationic centre. Phenylmethanethiol is a superior transfer agent for the preparation of crystalline or non-volatile sulfonyl chlorides or systems in which the carbon bearing the chlorosulfonyl group can bear positive charge with some facility.

In conclusion, we have developed thioglycolic acid as a new sulfur transfer reagent for sulfonyl chloride synthesis. Sulfonyl chloride synthesis requires substrate analysis in terms of (i) stability of carbocations which could be formed by S,1 dissociation of intermediate chlorosulfollium and oxochlorosulfonium cations, (ii) AX, for asymmetric sulfides for which neither carbon attached to sulfur is a potential carbocationic centre, and (iii) steric factors which may complicate the cleavage of a- polychloro-oxochlorosulfonium chloride intermediates.


The ir spectra were recorded on a Perkin-Elmer 237B spectrophotometer. The nmr spectra were obtained on a Varian T-60 instrument using TMS as the internal standard. The mass spectra were recorded on a Dupont-CEC model 21-104 mass spectrometer. The samples were directly introduced using an all glass probe and the spectra run at 30 eV with a source temperature of 150'C. Melting points were determined on a Fisher-Johns melting point apparatus and are uncorrected.

E.ulznustice Chlorinntions 111 Aqueo~ls Mediunz The sulfide substrate was dissolved in glacial acetic acid

(25 mL) and water (3 i11L). Chlorine (ca. 200 mL/min) was bubbled into the reaction mixture for 2.5 h with iceiwater cooling as necessary to maintain the temperature of the reaction lnixture between 20 and 30 C. Water (50 mL) was added and the resultant mixture washed with methylene chloride (100mL). The organic layer was washed with 2.5% wiv NaOH (two 50 mL aliquots), dried (MgSO,), filtered, and the solvent evaporated. The residue was distilled or recrystallized before yield was determined.

Pi,epamtion of PIzCH2CH2SCH3 Sodium metal (0.851 g) was dissolved in absolute ethanol

(100 mL). Methanethiol (5 mL) was slowly distilled into the cooled ethoxide solution. 2-Phenyl-1-chloroethane (5.021 g) in ethanol (10 mL) was added dropwise over 15 min and the rcaction mixturc stirred at ambient temperature for 48 h. Water (100 mL) was added and the resultant mixture washed with chloroform (three 100 mL aliquots). The combined organic layers were dried and concentrated. The crude concentrate was rectified at reduced pressure affording the sulfide (4.572 g, bp 96-C/5 Torr), nmr (CDCI,) 6 : 7.70 (5H, s), 3.00 (4H, m), and 2.10 (3H, s); ms n / e : 152 ( M f , 28Y,), 91 (5373, and 61 (100%).

0

Preprri rrr~on of CH,SCH2CH2C-0CH3 4a Sodium metal (4 210 g) was dissolved 111 methanol (200 mL)

and the solution cooled Methaneth~ol (10 mL) was d~st~l led Into the reactlon m~xture and methyl acrylate (15 691 g) added The reactlon ln~xture wab refluxed 1 h Water (250 mL) was added and the lesultant m~r tu re washed w ~ t h chloroform (four 200 niL aliquots). The combined organic layers were dried and concentrated. The residue was distilled at reduced pressure yielding the sulfide ester (8.586 g, bp 106-108'Cl 100Torr), ir (CHCI,): 1740cm-'; nmr (CDCI,) 6 : 3.76 (3H, s), 2.73 (4H, m), and 2.13 (3H, s); ms m/e : 134 ( M f , 64%), 74 (98%), and 61 (100%).

Chlorination of Asymmetric Szilfides A series of asymmetric sulfides were subjected to aqueous

chlorinolysis as described under "Exhaustive Chlorinations". The relative yields were determined by integration of the nmr spectru~n of the crude product. Results are shown in Table 2.

Preparation of CH3SCH2 CH2 CH20H 5a Lithium aluminum hydride (1.701 g) was covered with

T H F (15 mL) and the mixture refluxed for 0.5 h. The mixture was cooled to room temperature and a solution of CH3S-

(CH2),C0,CH3 (6.000 g) in THF (10 mL) added dropwise over 10 min. The reaction mixture was refluxed for 0.5 h. Upon conipletion of the reflux ethyl acetate (2.5 mL) was added dropwise; 10% HCI (30 mL) was added dropwise, the layers separated, and the organic layer dried and concentrated. The residue was fractionated at reduced pressure furnishing the sulfide alcohol (4.238 g, bp 136-C/100 Torr), ir (CHCl,): 3620 and 3450cm-I; nmr (CDCI,) 6 : 3.76 (2H, t), 2.60 (2H, t), 2.33 (IH, s), 2.13 (3H, s), and 1.90 (2H, m); ms twe: 106 (M*, 100%), 88 (67%), and 73 (40%).

Preparation of PIIS(CH,)~CI 6b and CH3S(CH2)3CI 6a CH,S(CH,),OH or PhS(CH,),OH (15) (10 g) was dis-

solved in chloroform (40 niL) and the solution brought to gentle reflux. Thionyl chloride (1 equiv.) in chloroform (20 mL) was added dropwise to the reaction mixture over 10 min. Upon completion of the addition the reaction mixture was refluxed.

After 4.5 h reflux the solvent was renloved and the residue distilled affording PhS(CH,),CI (4.876 g, bp 13OCC/2.2 Torr), nmr (CDCI,) 6: 7.20 (5H, s), 3.60 (2H, t), 3.03 (2H, t), and 2.00 (2H, m); ms m:e: 188 (19%), 186 (Mf , 5773, 123 (loo%), and 110 (82%).

After 24 h reflux the solvent was removed and the residue rectified yielding CH3S(CH2),C1 (8.309 g, bp 114-1 16'Ct 100 Torr), nmr (CDCI,) 6: 3.70 (2H, t), 2.70 (2H, t), 2.13 (5H, m); ms t71/e: 126 (4.473, 124 ( M t , 13.3%), 88 (42%), and 61 (100%).

Preprrration ~ ~ P / I S O ~ ( C H ~ ) ~ C I 7b and CH3SO,(CH2),C1 7a Chronliunl trioxide (2.5 equiv.) was covered with glacial

acetic acid (140 mL) and a solution of the appropriate chlorosulfide (5.00 g) in glacial acetic acid (10 mL) added. The reaction mixture was cigorouslj~ stirred and the temperature maintained at 90-100-C for 0.5 h. Water (150 mL) was added and the resultant mixture washed with methylene chloride (four 100 mL aliquots). The combined organic layers were washed with 5% NaOH (100 n1L aliquots) until the aqueous layer remained basic. The organic layer was dried, concentrated, and the residue distilled.

CH3SO2(CH2),C1 (3.816 g, bp 168-170 Ci4 Torr) had ir (CHCI,): 1325 and 1145 cm-'; nrnr (CDCI,) 6: 3.80 (2H, t), 3.26 (2H, t), 3.00 (3H, s), and 2.20 (2H, m); ms m,'e: 158 (3.1%), 156 ( M t , 9.373, 94 (60%), and 41 (100%).

PhSO2(CHZ),C1 (3.139 g, bp 180-182"C/1.9 Torr) had ir (CHC1,): 1325 and 1150 cm-' ; 11111r (CDCI,) 6 : 7.80 (5H, m), 3.60 (2H, t), 3.30 (2H, t), and 2.20 (2H, m); ms rille: 220 (2.7%), 218 (M+, 8.1%), 77 (loo%), and 41 (57%).

Preyai.ution of Sulfide Acids 1 The preparations of the sulfide acids were all carried out in

the same manner as illustrated for the preparation of the methyl system la . The crude samples were checked to confirm that the expected product had formed. Sodium metal (0.407 g) was dissolved in methanol (25 mL) and thioglycolic acid (0.807 g) added. A solution of methyl iodide (1.216 g) in methanol (1OmL) was added dropwise and the reaction mixture stirred at ambient temperature for 24 h. The solvent was evaporated and the residue tlzor.o~rghly dried. Water (5 mL) was added, followed by concentrated HC1 (1 mL). Chloroforn~ (250 mL) was added, the solution dried (Mg- SO,), filtered, and concentrated affording crude sulfide acid.

Preparation of CH3 CH2SCH2 C 0 2 CN, Crude sulfide acid was prepared from ethyl bromide

(4.264 g), thioglycolic acid (3.614 g), and sodium metal (1.866 g) in methanol (60 mL) as described for the sulfide acids 1.

The crude acid was covered with methanol (5 mL) and concentrated HC1 (6 mL). The reaction mixture was stirred at ambient temperature for 5 min. Chlorofornl (250 mL) was added and the mixture dried (MgSO,), filtered, and concentrated. The residue was rectified at red~lced pressure affording the sulfide acid methyl ester (1.820 g, bp 106-108'C/ 100 Torr); ir (CHCI,): 1730 cm-I ; nrnr (CDCI,) 6: 3.73 (3H, s), 3.23 (2H, s), 2.66 (2H, q), and 1.26 (3H, t); ms nzle: 134 ( M t , 38.0%), 75 (loo"%,), and 74 (60%). Anal. calcd. for C,H,,O,S: C 44.75, H 7.51; found: C 44.25, H 7.73.

CH3SCH2C02H l a had ir (CHCI,): 3000 and 1720 cm-'; nrnr (CDCI,) 6: 11.53 (IH, s), 3.23 (2H, s), and 2.26 (3H, s): ms m/e: 106 ( M t , 44%) and 61 (100%).

CH3CH2SCH2C02H had ir (CHCI,): 3000 and 1720 cm-' ; nmr (CDCI,) 6 : 11.50 ( lH , s), 3.26 (2H, s), 2.70 (2H, q), and 1.26 (3H, t).

CH3(CH2),SCH2C02H had ir (CHCI,): 2990 and 1720 cm- ' ; nrnr (CDC1,) 6 : 11.09 (IH, s), 3.26 (2H, s), 2.66 (2H, t), 1.73 (2H, m), and 1.00 (3H, t); ms m/e: 134 ( M f , 50%), 75 (loo%), and 47 (86%).

CH3(CHZ),SCH2CO2H had Ir (CHCI,): 3000 and 1720 c m - 5 nmr (CDCI,) 6: 11.10 (IH, s), 3.50 (2H, s), 2.70 (ZH, t), 1.60 (4H, m), and 1 .OO (3H, t) ; ms nl/e : 148 (M t , 5 I%), 89 (78%), 61 (51%), and 47 (100%).

CH3(CH,),SCH2C02H had ir (CHCI,): 3000 and 1720 cm-I ; nmr (CDCI,) 6: 11.23 ( lH, s), 3.23 (2H, s), 2.66 (2H, t), 1.40 (6H, m), and 0.90 (3H, t); nis mje: 162 ( M t , 3773, 103 (8021, and 69 (100%).

CH3(CH2),SCH2C0,H had ir (CHCI,): 3000 and 1720 cm-I ; nmr (CDCI,) 6 : 11.37 (IH, s), 3.23 (2H, s), 2.66 (2H, t), 1.40 (8H, m), and 0.90 (3H, t); ms t11,'e: 176 ( M t , 3421, 117 (loo%), and 83 (64%).

CH3S02(CH2)3SCH,C02H had Ir (CHCI,): 3000 and 1720 cni- : nrnr (CDCIA 6: 11.30 l lH. s). 3.30 (2H. s). 2.96 (7H, ni), and 2 .16 ' (2~, m); ms m/e: 195(27%), 121 (27%), and 73 (IOOZ).

PhS02(CH2),SCH2C02H had ir (CHCI,): 3000 and 1720 cm-' ; nrnr (CDCI,) 6 : 11.45 (IH, s), 7.90 (5H, m), 3.26 (4H, m), 2.83 (2H, t), and 2.13 (2H, m); ms m/e: 256 (50%), 143 (82%), and 77 (100%).

(CH3),CHSCH2CO2H Ib had ir (CHCI,): 3000 and 1720 cm-' ; nrnr (CDCI,) 6: 11.25 ( lH, s), 3.33 (3H, m), and 1.30 (6H, d); nis m/e: 134 (M?, 55%), 92 (42%), and 75 (100%).

Chlorinolysis of l a Crude sulfide acid l a (0.93 g) was chlorinated for 10 min

employing the procedure outlined under "Exhaustive Chlori- nations". Trichloromethyl methyl sulfoxide (1.212g) was obtained. After purification by column chromatography employing silica gel and chloroform elution, the product was shown to be identical to authentic material by nmr, ir, and tlc.

Chlorincrtiort of Sulfide Acids The desired alkyl sulfide acid (5 g) was chlorinated as

described under "Exhaustive Chlorinations" and the alkane sulfonyl chloride products distilled. In each case the product had the known ir, nmr, and bp. Overall yields for conversion of the alkyl halides into the corresponding sulfonyl chlorides are given in Table 4.

CH3S0,(CH2),S02C1 30 was recrystallized from chloroform and had mp 62-65,C; ir (CDCI,): 1380, 1310, 1170, and 1145 cm- l ; nrnr (CDCI,) 6 : 3.96 (2H, t), 3.26 (2H, t), 2.96 (3H, s), and 2.56 (2H, t); ms tnle: 143 (6.821, 141 (20.4%), 79 (13.3%), and 41 (100%). Anal. calcd. for C,H,C10,S2: C 21.76, El 4.11; found: C 21.35, H 4.18.

LANGLER ET AL. 3199

PhS02(CH2)3S02C1 36 was recrystallized from chloroform and shown to be identical to previously prepared material (15) by ir, nmr, mp, and mixture mp.

Cl~lo~.itzarion of (CH,) ,CHSCH2CO2H I b T h e sulfide acid (4.71 g) was subjected t o the procedure

outlined under "Exhaustive Chlorinations". The crude product contained 2-acetoxypropane (1.499 g), 2-propanesulfonyl chloride (2.284 g), and dichloromethanesulfonyl chloride (2.509 g) as determined by a method described previously (4). The identity of the constituents in the mixture was confirmed by the addition of authentic samples of each conlpound which resulted in the change of the intensities of the appropriate signals in the nmr spectrum of the mixture.

Chlorinariorr of (CN,) ,CHSCHzPlz The benzylic sulfide (5.84 g) was subjected to the procedure

outlined under "Exhaustive Chlorinations". The crude product contained 2-propanesulfonyl chloride (4.281 g). The identity of the sulfonyl chloride and benzyl chloride were confirmed by the addition of authentic samples to the crude which resulted in the change in intensities of the appropriate signals in the nmr spectrum of the mixture. N o isopropyl acetate was present in the crude.

The authors are indebted to Mr. T. P. Ahern for some technical assistance and to Dr. J. H. Kim for running the mass spectra. We are grateful to Dal- housie University for financial support in the form of a grant from the Research Development Fund.

1. ( 0 ) T. P. AHERIL. D. G . K A ) . and R. F. LANGLER. Can. J. Chem. 56,2422(1978): ( b ) D. G . K A Y . R. F. L ~ I \ G L ~ R . and J . E. TREYHOLM. Can. J. Chem. 57.2185 (1979).

2. R . F. LAUGLER. Z. A. MARINI . and J . A. P I ~ C O C K . Can. J . Chem. 56.903 (1978).

3. J . S . GROSSERT. W. R. HARDS~IAFF, and R. F. L A ~ G L ~ K . Can. J . Chem. 55,421 (1977).

4. J . S. GROSSERT and R. F. LANGLER. Can. J . Chenl. 55,407 (1977).

5. R. F . LAYGLER. Can. J . Chem. 54.498(1976). 6. W. R. HARDSTAFF, R. F. LA\GLLR, J . L E A H Y , and M. J .

NE\VI\IAN. Can. J . Chem. 53.2664(1975). 7 . 5. S. GROSSERT, W. R. HARDSIAFF. and R. F. LANGLER.

Chem. Commun. 50 (1973). 8 . J . S . GROSSERT and R. F . LANGLER. Chem. Commun. 49

(1973).

9. J . MARCH. Advanced organic chemistry. McGraw-Hill. New York. NY. 1968. pp. 373,374.

10. J . F. KIYG. Acc. Chem. Res. 8, 10 (1975). 11. W. E. T R U C ~ and A . M. MURPHY. Chem. Rev. 48. 69

(1951). 12. J . L. K I C t . in The chen~istr> of organic sulfur compounds.

Editril b? N . Kharasch and C. Y. hleycrs. Pergamon. NY. 1966. pp. 120. 121.

13. M. ASSCHER and D. VOFSI. J . Chem. Soc. 4962(1964). 14. F. G. BORD\\'LLL and H . M. AUDERSEN. J . Am. Chem.

Soc. 75,6019 (1953). 15. H . 0. Fo\o. W . R . HARDSTAFF. D. G . KAY. R. F. LA\G-

LER. R. H . MORSE.. and D. N . SANLIOVAL. Can. J . Chern. 57. 1206 (1979).

16. 6. OLAH. Friedel-Crafts and related reactions. Vol. 3. Part 2. Interscience, NY. 1964. p. 1319.

17. H . BURTO\ and W . A. DAVY. J . Chem. Soc. 528 (1948). 18. E . E. GILBERT. Sulfonation and related reactions. Inter-

science, NY. 1965. pp. 84 and 126. 19. L . A. P A Q U E T T ~ and R. B. HOUSLR. J . Am. Cheni. Soc. 91.

3870 (1969). 20. H. BR~NIZI \GER. H. KODDEBCSCH. K . KLILG. and G .

SUNG. Ber. 85.455 (1952). 21. 1 . B. DOUGLASS. V. SIMPSO\. and A. S A W Y E R . J . Org.

Chem. 14.272 (1949). 22. I . B. D o u c r s s and T. B. JDH%SON. J . Am. Chem. Soc. 60.

1486 (1938). 23. T . B. JOHYSON and J . M. SPRAGUL. J . Am. Chem. Soc. 58,

1348(1936). 24. T . B. JOHNSO% and I . B. D ~ U G I sss . J . Am. Chem. Soc. 61.

2548 (1939). 25. I . B. D o u c ~ l i s s . B. S. FARAH. and E . G. THOXIAS. J . Org.

Chem. 26. 1996 (1961). 26. I . B. D o u c ~ ~ s s a n d C. E. OSBORYE. J . Am. Chem. Soc. 75.

4582 (1953). 27. R . OTTO. Ann. Chern. 145,323 (1868). 28. W . TAGAKI. It? Organic chemistry of sulfur. Eilitc.d S.

Oae. Plenum Press. New York. NY. 1977. p. 231. 29. J . R . C ~ M P B E L L . J . Org. Chem. 29. 1830(1964). 30. 51. S. KHARASCH. E . N . MAY. and F. R. MAYO. J . Org.

Chem. 3. 189 (1940). 31. J . Bu.1LE.R and R. M. K ~ L L O G G . J . Org. Chem. 12. 973

(1977). 32. J . E. H U H ~ E ~ . J . P h y s Chem. 69.3284(1965). 33. J . E. HUHEEY. J . Phys. Chem. 70.2086(1966). 34. ( ( I ) K . C . T I N and T. D U R ~ T . Tetrahedron Lett. 4643 (1970):

(h) T. DURST. K. C . T I N . and M. 5 . V . MARCIL.. Can. J . Chem. 51. 1704 (1973).

35. M. C I ~ Q U I ~ I and S . COLO>YA. J . Chem. Soc. Perkin Trans. I , 1883 (1972).

Intermediate stages of the sulfohaloform reaction. Preparation sf a-halosulfoxides and sulifinyl chlorides. Oxygen-transfer reactions

J . STUART GROSSERT, WILLIAM R. HARDSTAFF, A ~ D RICHARD F. L A ~ G L E R Chernrrtr~ Deprirrmer~r, Drilhorrsre U ~ I I L ersro, Hallfak, A S , Car~citftr B3H4J3

Recelved October 10, 1975'

J. STUART GROSSERT, WILLIAM R. HARDSTAFF, and RICHARD F. LANGLER. Can. J. Chem. 55, 421 (1977).

Details are provided of synthetic routes from dialkyl sulfides to both a-halosulfoxides and sulfinyl chlorides. In the case of the former, oxidation of cr-halosulfides to the sulfoxide stage is achieved by chlorine in acetic acid containing controlled amounts of water. Sulfinyl chlorides are prepared by chlorination of a-polyhalosulfoxides in methylene chloride. During investigations into the details of the sulfohaloforn~ reaction, a number of novel redox reactions involving oxygen transfer between sulfur species have been observed and these are presented. They include a reduction of a sulfoxide with thionyl chloride.

J. STUART GROSSERT, WILLIAM R. HARDSTAFF et RICHARD F. LANGLER. Can. J. Chern. 55, 421 (1977).

On fournit des details permettant de synthetiser a la fois les a-halosulfoxydes et les chlorures de sulfinyles a partir des sulfures de dialkyles. Dans le premier cas, I'oxydation des sulfures a-haloginis en sulfoxyde est effectuee par du chlore dans de l'acide acetique contenant des quantites contr61Ces d'eau. On prepare les chlorures de sulfinyles par chloruration de sulfoxydes a-polyhalogenes dans le chlorure de methylene. Au cours des etudes effectukes afin d'elucider les dktails de la reaction sulfohaloformique, on a observe un certain nombre de nouvelles reactions d'oxydo reduction impliquant un transfert d'oxygtne entre des especes contenant du soufre; on presente ces nouvelles reactions. Elles colnprennent une reduction d'un sulfoxyde par le chlorure de thionyle.


Synthesis of a-Polyehlorosulfoxides Sulfoxides are usually synthesized by the con-

trolled oxidation of sulfides (1,2). Such a reaction always has the potential of giving higher oxidation products, for example, sulfones, and there is ample literature documentation of reactions designed to avoid such complications (2, 3). Initial investigations of the use of halogens in aqueous media to oxidize sulfides deinonstrated that molecular bromine afforded much smoother and more readily controlled reactions than did molecular chlorine (ref. 1, p. 216). Since the work of Fries and Vogt in 191 1 (4), no further attempts appear to have been made to use chlorine for the oxidation of sulfides to sulfoxides.

The excessive reactivity of chlorine becomes an advantage, however, when the oxidation of heavily chlorinated sulfides is attempted since the

R,RZR3C.S0.CH2R4

1 R1 = C1; R2 = R3 = R4 = H

2 R, = R Z = C 1 ; R 3 = R 4 = H


low nucleophilicity of such sulfides introduces a rate retardation, in comparison to that of unchlorinated sulfides, which makes the reaction easy to control. The complication involved in chlorinating more nucleophilic sulfides and sulfoxides is that the product is often nearly as reactive as the starting material. For example, chlorination of DMSO in aqueous acetic acid, a t room temperature, leads to the formation of i - chloro-2-thiapropane-2-oxide, 1, which is seri- ously contaminated with 1,l-dichloro-2-thiapropane-2-oxide. 2. The desired control for the oxidation of sulfides with chlorine in aqueous media does not obtain until the starting sulfide has a t least two a-chlorine atoms. Thus controlled chlorination of 1,3-dichloro-2-thiapropane furnished the corresponding sulfoxide 3 without difficulty ( 5 ) .

In a typical experiment, the polychlorosulfide

C 4 N . J. CHEM. VOL. 55. 1977

TABLE 1. Preparation of a-polychlorosulfoxides from a-polychlorosulfides by chlorination (232 ml/min) in glacial HOAc containing 3 equiv. of water

Yield Chlorination Starting sulfide Sulfoxide product (%I time (min)

(cri. 16 gm) was dissolved in acetic acid (50 ml) and 3 equiv. of water were added. Chlorine was bubbled into the solution and the temperature maintained at 25 to 30 "C. The results obtained on the systems utilized in this study are given in Table 1.

Many reagents available for the conversion of sulfides to sulfoxides give rise to some sulfone as well (2, 6). Although the preparation of a-polychlorosulfoxides utilizing chlorine and aqueous acetic acid is not complicated by sulfone formation, it is normally complicated by sulfonyl chloride formation. However, sulfonyl chloride formation occurs as a minor side reaction and the sulfonyl chloride can be readily removed by washing the sulfoxide with aqueous base. By contrast, sulfones are often difficult to remove from the corresponding sulfoxide, particularly when purification is attempted by recrystallization (6).

A useful modification of this synthetic method involves the conversioil of a sulfide to the corresponding a-chlorosulfoxide in one step. Since chlorosulfonium chloride salts are inert t o acetolysis (7), the starting sulfide can be chlorinated in glacial acetic a c ~ d to furnish the homologous a-chlorosulfide. After the addition of water further chlorination affords the corresponding sulfoxide. In this way, 1,3-dichloro-2- thiapropane has been converted routinely into 1,1,3-trichloro-2-thiapropane-2-oxide, 4, in 50% yield.

Synthesis of Sulfinyl Chlorides The development of synthetic methods for the

preparation of sulfinyl chlorides has received relatively little attention. Most sulfinyl chlorides have been made by variations of the same reaction developed by Douglass, namely the controlled solvolysis of alkyldichlorosulfonium chloride salts (8,9). The chief difficulties with this

method center around finding a suitable solvent in which to carry out the solvolysis. For example, when acetic acid is employed as the solvent, excess chlorine initiates a slow but smooth transformation of the sulfinyl chloride into the corresponding sulfonyl chloride. However, this problem seems to have been overcome by employing acetic anhydride for the solvent. Using a different synthetic method, some aromatic sulfinyl chlorides have been prepared by reaction between the sulfinic acid and thionyl chloride (10).

Our studies on the cleavage of a-polychlorosulfoxides with chlorine (5) led to the selection of methylene chloride as the solvent in order to prevent solvolysis reactions. The results of the initial examination of this reaction indicated that a-trichlorosulfoxides would undergo facile cleavage when treated with chlorine in methylene chloride, whereas a-dichlorosulfoxides would not undergo cleavage in useful yields.

A summary of the sulfoxide substrates examined is presented in Table 2.

It is noteworthy that the yield of sulfinyl chloride from chlorination of phenyl trichloromethyl sulfoxide was poor and that the compound could not be separated intact from the reaction mixture. This observed poor yield and the long chlorination time are precisely what would have been expected from an alkyl u,a- dichloroalkyl sulfoxide. It appears, therefore, that the phenyl ring acts to suppress the electron- withdrawing effect of approximately one chlorine atom, which may be rationalized by postulating the delocalization in the intermediate oxochlorosulfonium chloride of positive charge on sulfur around the aromatic ring.

In its generalized form, this method of alkanesulfinyl chloride preparation requires that trichloromethyl alkyl sulfoxides be available. Since the chlorination of alkyl methyl sulfides normally

GROSSERT ET AL

TABLE 2. Preparation of alkanesulfinyl chlorides from a-polychlorosulfoxides by chlorination (232 ml/min) in CH2Cl2

Sulfinyl chloride Yield Chlorination Starting sulfoxide product (%I time (min)

C1CHz,SO.CHCl2 4 C1CH2.S0,Cl 72 30 CICH2.SO.CC13 5 ClCH2.SO.Cl 80 50 CH3.S0.CHC12 2 CH3.S0.CI 76 25 CH?.SO.CCl, 6 CH3.S0,CI 77 25

goes preferentially into the alkyl group ( l l ) , it might appear that this method is not generaliz- able on account of the lack of availability of the intermediate trichloromethyl sulfides. However, this is not so, since both chloromethyl and dichloromethyl aikyl sulfides are available through established methods. Bohme (12, 13) has developed the preparation of chloromethyl alkyl sulfides from alkyl thiols, paraformaldehyde, and HCI. More recently a method for the preparation of dichloromethyl alkyl sulfides from the thiol- formates and phosphorus pentachloride has been published by Holsboer and van der Veek (14). These authors have also reported the preparation of a number of trichloromethyl alkyl sulfides from the dichloromethyl alkyl sulfides.

It should be noted that the preferred method for the preparation of metha~lesulfinyl chloride utilizes 1,l -dichloro-2-thiapropane-2-oxide, 2, as starting material. Although the chlorination of 1,1,l-trichloro-2-thiapropane-2-oxide, 6 , has been examined and proceeds quite satisfactorily, 6 is considerably less convenient to prepare than is 2.

Oxygen-transfer Reactions Most of the reactions which we encountered

during our studies on the sulfohalofor~n reaction (5, 7 ) involved sulfur behaving as a nucleophile towards eiectrophilic chlorine. However, we also observed a number of reaction pathways in which sulfoxides acted as nucleophiles at oxygen. This type of reaction by sulfoxides is of course well documented (15, 16), but the reactions described below are novel and warrant a brief discussion.

Although chlorination of i,3-dichIor0-2-tllia- propane-2-oxide, 3, in dilute aqueous acetic acid was a relati.iely straightforward reaction yielding primarily 4 (5), the use of glacial acetic acid as solvent permitted the obser1-ation of a chlorinated sulfoxide behaving as an oxygen nucleophile in a more complex reaction. The products

shown in [I] were obtained. The previous report

+ C13C.S~CH2Cl (26%) + CHCI, (26%) 8

( 5 ) established that the chloromethanesulfony1 chloride, 9, is produced from the corresponding sulfinyl chloride which in turn is produced from the trichlorosulfoxide, 4. It is also clear that the sulfinyl chloride acquires an oxygen atom from a sulfoxide which is converted to the corresponding cx-chlorosulfide. The simplest assumption, since the isolated sulfide is in fact the tetrachlorosulfide 8, is that oxygen is transferred from the trichlorosulfoxide 4. Chlorination of the trichlorosulfoxide 4 in glacial HOAc furnishes no tetrachlorosulfide 8 as we have shown previously (5). It therefore follows that the oxygen transfer must have occurred from the dichlorosulfoxide 3. This reasoning was supported by chlorination of a -1 : 1 mixture in glacial acetic acid of chloro- nlethanesulfinyl chloride and the dichlorosulfoxide 3 which did indeed furnish the expected mixture of chloromethanesulfony1 chloride 9 and tetrachlorosulfide 8 in a 1 : 1 ratio. The pathway for the chiorination of the dichlorosulfide 3 in glacial acetic acid is depicted in Scheme 1.

It is interesting to compare the reactions of 3 (cf reaction 1 ) and 2 (reaction 2) (5) with chlorine in glacial acetic acid. No oxygen-

C12 [2] 2 - HOAc CH,,SOZ.CI (72%) t CC1, (72%)

transfer products were observed in 121. The differences between 2 and 3 may be explained by a number of factors. These include the fact that 2 undergoes rapid further chlorination to the less- nucleophilic trichlorosulfoxide 6 and the fact that in [I] , the oxygen transfer arises from the

CAN. J. CHEM. VOL. 55, 1977

CI, C1CH,.S0.CH2CI --A ClzCH.S0.CH2CI

HOAc 3 4

more nucleophilic sulfoxide 3 attacking the more C I ~ C H . S O . C H , CI,C. SO.CH,CI electrophilic oxodichlorosulfonium salt 10. This compares with [2] in which for a comparable process to occur, the predominant sulfoxide C1, / CH,CI, i Clz would be 6 and the comparable electrophilic species to 10 would be I1 (cf . Schemes 1 and 2).

That an oxygen-transfer reaction could occur CI3C'SO'CH3 C~CH:. SO.Ci + CCI,

in the case of dichlorosulfoxide, 2, was found by 6

a careful examination of its chlorination in 0 :a:- I II

methylene chloride solvent. The reaction is CH .I1+

depicted in [3]. J 1 11

cI2 CH3.S0.C1 + CCI, II

CI2CH.S.CH3 I31 2 7 CH,.SO.CI (75%) + CH, ,S02CI (1%)

CH,C12 2 ,

The chloromethanesulfinyl chloride must origi- nate from the tetrachlorosulfoxide 5 since methanesulfinyl chloride did not give rise to any :cj :- chloromethanesulfinyl chloride when chlorinated C1

I + '-\ + in methylene chloride. The selective oxidation of CI,CH CH, + SO, CI + C12CH,S ,CHI rnethanesulfinyl chloride to the sulfonyl chloride r" in the presence of chloromethanesulfinyl chloride :cI:- can be rationalized on the grounds that the concentration of methanesulfinyl chloride is much C I , ~ . s ,-H, -- Cl, C I , C . S . C H ~ C I greater during the reaction and that the methane- 8 sulfinyl chloride reacts at a faster rate with S C H E ~ I E 2

GROSSE

chlorine to form the oxodichlorosulfoniun~ chloride salt 11. A reasonable reaction pathway is outlined in Scheme 2.

It might have been expected that methanesulfinyl chloride would best be prepared by simple chlorination of DMSO, especially in light of the literature report that sulfoxides may be cleanly chlorinated in methylene chloride (17). However, in our hands, DMSO produced a plethora of products with chlorine in either methylene chloride or glacial acetic acid. T h ~ s is undoubtedly due to oxygen-transfer reactions. We did find that these processes could be sup- pressed to give a useful reaction by use of a controlled amount of water in the acetic acid (5).

We have also observed a novel oxygen transfer reaction which did not involve molecular chlorine. 111 1955, Bordwell and Pitt (18) examined the reaction of sulfoxides with thionyl chloride. Upon subjecting thiacyclopentane- 1 - oxide to the appropriate conditions, they reported the formation of "a dark colored material with a wide boding range". A reinvestigation of this reaction furnished the unexpected result that the major isolable product was thiacyclopentane (25% yield). As initially isolated, it was contaminated with a small amount of material that may have been the expected 2-chlorothiacyclopentane (nmr). Redistillation gave thiacyclopentane of satisfactory purity. This apparently unprece-

dented reduction of a sulfoxide by thionyl chloride (ref. 10, p. 341) can be rationalized as depicted in Scheme 3.


Details have been provided previously (5).

Preparation of Cl, CH.S0.CH2 Cl, 4 1,3-Dichloro-2-thiapropane (1 6.00 g) in glacial acetic

acid (50 ml) was chlorinated (232 ml/min) for 20 min. Water (6.6 ml) was added and C1, (232 ml!rnin) was bubbled through the reaction mixture for an additional 35 min. Water (75 nil) was added and the solution was extracted with chloroform (4 x 100 ml). The cornbinecl chloroform layers were washed with 2.5% NaOH until the p H of the aqueous layer remained basic, and then given a standard work-up. The residue was fractionated at reduced pressure to furnish 4 (11.08 g, 50%).

Chlorination of C13C,S0,CH2Cl, 5 5 (15.25 g) was dissolved in methylene chloride (50 ml)

and chlorine (232 ml/nlin) was bubbled through the reaction mixture for 50 min. The solvent was distilled off at atmospheric pressure and the residue was rectified at reduced pressure affordingchloromethanesulfinyl chloride 9 (7.62 g, 80.3%) bp 94 ' C 80 torr.

Chlorination of Cl,C.SO.C, H,, 7 7 (9.64 g) was dissolved in methylene chloride (50 nll)

and chlorine (232 mlln~in) was bubbled through the reaction mixture for 90 min. The methylene chloride was rotary evaporated to yield an orangish rcsiduc (10.02 g). Methanol (50 ml) was added to the residue and the solution stirred at ambient temperature for 60 min. The methanol was rotary evaporated affording a residue containing Ph,SO,OMe (1.90 g, 3973, unreacted Ph.SO.CC1, (2.25 g, 23Y,), as well as at least two other con~pounds. Some of this residue was chromatographed on two preparative-layer plates (150 mglplate) which were eluted with carbon tetrachloride. The lowest band (RF 0.12 detected by uv light) was removed, and chloroform extraction gave a partially crystalline residue (142.7 mg) which was about equal parts CI,C.SO.Phand Ph.SO.OMe. This residue was rechromatographed (plc, chloroform eluant), the lower band (R, 0.62) from which furnished methyl benzenesulfinate (66 mg), which was identical with authentic material by tlc, nmr, and ir, and the upper band (R, 0.83) from which furnished Ph,S0,CC13 7 (67 mg), identical with the starting material by tlc, nmr, and ir.

Chlorination of CICH,.SO. CH, CI, 3 3 (15.01 g) (5) was dissolved in glacial acetic acid (50nll)

and chlorinated (232 ml/min) for 30 min. The nmr of the crude showed that C1,C.SCH2C18 and C1CH2.S02CI 9 were presellt in a 1 : 1 ratio. Ice water (75 nil) was added and the solution extracted with chloroform (2 x 100 ml). The chloroform layer was extracted with 2.5% NaOH (100 ml aliquots) until the p H of the aqueous layer remained basic. Standard work-up gave a residue which was fractionated at reduced pressure affording CI3C,S.CH,CI 8 (5.47 g, 26.4%) and Cl,CH~SO~CH,CI 4 (3.72 g, 19.6%). Both compounds were identical with authentic sanlples by nmr, ir, and bp.

426 C A N . J . C H E M . VOL. 5 5 . 1977

The reaction was repeated. After addition o f water and chloroform extraction, a portion o f the chlorofor~n solution (50 ml ) was continuously extracted with water2 for 24 h . The chloroform was dried (MgSO,), filtered, and concentrated and a portion o f the residue (500 mg) was added drop-wise to a chilled solution o f vanillin (218 mg) in dry pyridine ( I ml). After the reaction mixture was stirred at ambient temperature for 1 h , work-up in the usual way gave a residue which was chromatographed on five preparative-layer plates usingether-chloroform, 5 : 95. Extraction o f the band visible under uv light furnished vanillin chloromesylate (152 mg) which was identical with authentic material by tlc, ir, and nmr.

Clzlorirtafion of CI,CH.SO.CH,, 2 2 (16.81 g) in rnethylene chloride was chlorinated (232

ml/min) for 25 min. The methylene chloride was distilled o f f at atmospheric pressure and the residue was fractionated at 34 torr. Methanesulfinyl chloride (bp 52- 54 'C:34 torr) was removed and a residue (1.00 g) was obtained. Nuclear magnetic resonance spectra indicated the presence o f Cl,C~S~CH,CI 8 (264 mg, 1.273, CICH2.S0.C1 (437 mg, 2.9%), CH3.S02.C1 (163 mg, 1 .2x) , and CH,.SO.Cl (139 mg, 1.273. The crude residue was treated with vanillin (1.002 g) in pyridine (2.5 mi) as outlined previously, the product o f which was evacuated (0.45 torr) and immersed in an oil bath (which had been preheated to 100 'C) , for 2 min. Condensation o f the distillate in a cold trap (- 50 ' C ) furnished 8 (153 mg) identical to authentic material by nmr, ir, and bp. The residue from the bulb-to-bulb distillation weighed 498 mg. A portion o f the residue (200 mg) was chroinatographed on two preparative tlc plates (silica gel HF-254) which were developed with 573 ether in chloroform. Vanillin mesylate (32.3 mg, R F 0.50) was isolated and shown t o be identical to authentic material by ir, nmr, and tlc.

The chlorination was rerun and a portion o f the distillation residue (250 mg) was chlorinated (232 mljmin) in distilled water (1.7 ml) for 5 min. The reaction mixture was diluted to 10 ml with distilled water and extracted with chloroform (3 x 10 ml). Standard work-LIP gave a residue which was treated with vanillin (200n1g) in pyridine (1.0 ml) as described previously. Vanillin chloromesylate (48.2 mg. R F 0.55) was isolated by preparative-layer chromatography, as outlined above and was shown to be identical to authentic material by nmr, ir, and tlc.

Renrtion of Tl~iacyclopenfa~~e-I-o.~ide cmd SOC/, Thiacyclopentane-I-oxide (28.85 g) was dissolved in

'The water was distilled from 5% NaOH to prevent recycling o f the acetic acid.

methylene chloride (40 ml) and was added drop-wise over a period o f 1 % h to a gently refluxing solution o f thionyl chloride (34.89 g) in methylene chloride (40 ml). Upon completion o f the addition the reaction mixture was fractionated and the material (7.32 g) which had bp 90- 120 ' C was collected. Redistillation furnished clean thiacyclopentane (bp 116-120 ' C , 3.65 g) which was identical with authentic material by bp, nmr, and ir.

Acknowledgements We thank Mr. J. Leahy for technical assistance

and the National Research Council of Canada for financial support, as well as for the award of a Postgraduate Fellowship to one of us (R.F.L.).

1 . A . SCHOBERL and A . WAGNER. In Methoden der or- ganischen Chemie (Houben-Weyl). Vol . 9. Edited by E . Miiller. G . Thieme. Stuttgart. 1955. p. 21 1 .

2. H. H . SZMANT. I12 Organic sulfur compounds. Vol. 1 . Editeclby N . Kharasch. Pergamon. N . Y . 1961.p. 154.

3 . G . C. BARRETT. In Organic compounds o f sulphur. selenium, and tellurium. Chem. Soc. Spec. Publ. London. 1,71 (1970); 2.35 (1973).

4. K . FRIES and W . VOGT. Justus Liebig's Ann. Chem. 381. 337 (1911).

5. J . S . G R ~ S S E R T and R. F . LANGLER. Can. J . Chem. This issue.

6 . F. G . B ~ R D W E L L and P . J . BOUTON. J . .4m. Chem. Soc. 79.717 (1957).

7 . J . S . GROSSEKT. W . R. HARDSTAFF, and R. F. LANG- L E R . J . Chem. Soc. Chem. Commun. 50(1973).

8. M. L . KEE and I . B. DOGGL.~SS. Org. Prep. Proc. 2, 235 (1970).

9. C . G . V E K I E R . H. H. H S I E H , and H . J . BARAGERIII. J . Org. Chem. 38. 17 (1973).

10. J . S. PIZEY. Synthetic reagents. Vol . 1 . Ellis Hor- woodIJ. Wiley. Chichestel-. 1974. p. 336.

11. D. L. TULEEY and T . B. S T E P I I E K S . J . Org. Chem. 34. 31 (1969).

12. H. BOHML. Bei-. Dtsch. Chem. Ges. 69, 1610 (1936). 13. H. BOHME. H. F I S H E R , andR. FRANK. J U S ~ L I S Liebig's

Ann. Chem. 563.54 (1949). 14. D. H. HOLSBOER and A . P . M. vi\r D E R V E E K . Recl.

Trav. Chim. Pays Bas. 91,349 (1972). 15. T . DLRST. Adv. Org. Chem. 6.285 (1969). 16: W . S . MACGREGOR. Q. Rep. Sulfur Chem. 3. 149

(1968). 17. K . C . T I N and T . DUKST. Tetrahedron Lett. 4643

(1970). 18. F . G . B ~ R D W E L L and B. P . PITT. J . Am. Chem. Soc.

77,572 (1955).

Mechanisms in the chlorinolysis of sulfinyl chlorides

TERENCE PATRICK AHERN, MICHAEL FRANCIS HALEY, RICHARD FRANCIS LANGLER,' AND JUNE ELLEN TRENHOLM Department of Chemistry, Mount Allison University, Sackville, N.B., Carlacla EOA 3C0

Received February l I , 1983'

TERENCE PATRICK AHERN, MICHAEL FRANCIS HALEY, RICHARD FRANCIS LANGLER, and JUNE ELLEN TRENHOLM. Can. J . Chem. 62, 610 (1984).

The successful synthesis and chlorinolysis of a-mercaptodimethyl sulfone have provided additional support for our contention that Pummerer rearrangements may occur during the chlorinolyses of a-sulfonyl sulfinyl chlorides. Further exploration of chlorinolyses of a-sulfonyl systems has uncovered the first observations of CS bond cleavage during the chlorinolyses of (i) a sulfinyl chloride and (ii) a sulfinate ester.

TERENCE PATRICK AHERN, MICHAEL FRANCIS HALEY, RICHARD FRANCIS LANGLER et JUNE ELLEN TRENHOLM. Can. J. Chem. 62, 610 (1984).

Le fait que des a-mercaptodimCthylsulfones aient pu Stre chlorolysCes fournit une preuve additionnelle a notre suggestion que des transpositions de Pummerer peuvent se produire lors de la chlorolyse de chlorures d'a-sulfonylsulfinyles. Une Ctude plus poussCe de chlorolyses de systkmes a-sulfonyles a permis de mettre en Cvidence les premikres observations de rupture de liaisons C-S au cours de chlorolyses (i) d'un chlorure de sulfinyle et (ii) d'un ester sulfinate.


Introduction Some time ago ( I ) , we reported the results of a study on the

chlorinolysis of the sulfone-sulfide 1 as shown in eq. [I].

CIZ/HxO [I] PhCH2SCH2SOzCH3 - CH3S02CC12SOzCI

HOAc + PhCHzCl

1 2 Our proposal for the pathway of this reaction involved the intermediacy of the sulfenyl chloride 3 a and the sulfinyl chloride 3b.

CH,.SOz.CH?.S.CI CH3. SOz. CHC1. SO. CI 3a 3b

CH3.SOz.CHZ.S.S.Ph CH3.SOz.CHZ.S H I 3c 3d

Subsequently, we have undertaken the synthesis of a variety of potential intermediates and intermediate precursors which resulted in the successful preparation of 3 c (2). Chlorinolysis of 3c, as w e have pointed out (2), is very likely to produce 3a and does furnish the sulfone-sulfonyl chloride 2 as we had hoped.

We wished to pursue this problem further in the hope that w e could establish the intervention of an unprecedented process in the chlorinolysis of sulfinyl chlorides, viz. facile Pummerer rearrangement of a dichlorooxosulfonium cation (3a).

Results and discussion Our initial efforts were focused on the preparation of the

I mercaptosulfone 3d. One of the earlier attempts is shown in e q PI.

Pyridine [2] CHzSCH2CI + AcSH - CHzSCH2SAc

'Author to whom correspondence should be directed at: Department of Chemistry and Chemical Engineering, Florida Institute of Technology, 150 West University Boulevard, Melbourne, Florida 32901, U.S.A.


Attempts to deacetylate the sulfone-thiolacetate with H20/ -OH, LiA1H4, or NaBH4 furnished complex mixtures a n d were abandoned. The successful conversion of the sulfide- thiolacetate into the corresponding sulfone-thiolacetate suggests that acetyl groups may have use in protecting mercaptans when peroxidic oxidation of substrates is intended to alter other functional groups.

The successful synthesis of 3 d was accomplished as shown in Eq. [3].

Pyridine [3] CHzSOzCHzSSPh + PhSH -CH3SO2CH2SH + (PhS)?

CH'Cll

The mercaptosulfone 3d appears to be the first known a-mercaptosulfone. As expected on the basis of the properties of the corresponding a-mercaptosulfide 3 e (4), the oily mercaptosulfone 3 d decomposed at room temperature depositing crystalline material which was insoluble in all common organic solvents (tl12 = 6 days). W e presume that the crystalline material was polymeric thioformaldehyde.

Aqueous chlorinolysis of freshly prepared 3d produced the sulfone-sulfonyl chloride 2 in a reaction which must involve the sulfone-sulfenyl chloride 3a as shown in e q . [4].

CIz/H?O [4] CH?SO2CH2SH - [CH3SOzCH?.SCI]

HOAc

While the results shown in eq. [4] prove our contention that 3a would be transformed into 2 under the reaction conditions employed for the reaction shown in eq. [I], thus confirming 3a as a possible intermediate for that reaction, further examination of the pathway followed by 3 a in this reaction would require the and chlori~olysis ("in an anhydrous medibm" (2)) of other potential intermediates (e.g. t h e sulfone-sulfinyl chloride 3b) .

Earlv svnthetic efforts aimed at 3 c were unsuccessful until - , w e adopted an approach which accomplished skeletal modification using a chlorinolysis step followed by a dechlorination step carried out on the appropriate ester. Consequently, w e began our efforts to produce the possible sulfone-sulfinyl chlo-

AHERN ET AL. 61 1

.. I . . <,>\O R R-S,

X

ride intermediates for the reaction in eq. [ I ] by preparing the sulfone-sulfinate ester 5 as shown in eq. [5].

CHZOH - CH,S02CCIZ. SO. OCH3

5 In addition to the spectroscopic evidence obtained for the structure of 4, we have subjected it to hydrolysis which was accom- panied by desulfinylation as shown in eq. [6].

[6] CH3SO2CCl2.SO.CI + Hz0 + CHSOzCHClz 4 6

This behaviour parallels that observed for the hydrolysis of 2 (1) and is entirely consistent with the intermediacy of a sulf in~c acid which has anion stabilizing groups on C ( l ) (5).

While the chlorinolysis of sulfenate esters (vide eq. [5]) is precedented (6, 7), previous groups were unable to isolate the expected sulfinyl chlorides. Our conversion of 3 f to 4 appears to be the first report of the successful isolation of a sulfinyl chloride from a sulfenate ester chlorinolysis. Chlorinolysis of a sulfenate ester produces an 0-alkylated oxochlorosulfonium cation. Douglass and Poole (8) have produced 0-alkylated oxochlorosulfonium cations by the alcoholysis of dichlorosul- fonium cations. The two approaches for generating 0-alkylated oxochlorosulfonium cations are depicted in Scheme 1 (X = : ).

0-Alkylated dioxochlorosulfonium cations may be produced in similar manner (see Scheme 1; X = 0 ) . The usual fate of 0-alkylated dioxochlorosulfonium cations involves nucleophilic attack at carbon with resultant C O bond cleavage (3b).

Clz [7] PhCH2CHz. SO .OCH3 - PhCHzCHzSOzCl + [CH3C1]

CH2C12

Expecting to obtain the sulfonyl chloride 2, we have chlorinated the sulfinate ester 5 in order to obtain some simple chemical support for the structure of 5 . The unexpected observation of CS bond cleavage in the chlorinolysis of 5 prompted us to chlorinate the sulfinyl chloride 4 which furnished a similar result, as shown in Scheme 2.

C S bond cleavage is a well-known process in the chlorinolysis of sulfoxides (3). a-Polychlorosulfoxides are particu-

larly prone to undergo CS bond rupture pursuant to oxochlorosulfonium cation formation. Nucleophilic attack on the oxochlorosulfonium cation at the a-carbon bearing chlorine is usually the exclusive process. It is clear, however, that severe steric hindrance at the a-carbon bearing chlorine can shift some nucleophilic attack to the a'-carbon (9). A reasonably close sulfoxide relative of 4 has been shown to furnish 1 , l ,I-trichloro-2-thiapropane-2,2-dioxide in good yield (9) (see Scheme 3, pathway b).

In view of the results available from sulfoxide chlorinolyses, the rupture of a CS bond during the chlorinolysis of 4, while unprecedented, is not surprising. However, the results from the chlorinolysis of the sulfone-sulfinate ester 5 are remarkable indeed. Not only is the methyl group attached to oxygen (the usual electrophilic site in an 0-alkylated dioxochlorosulfonium cation) much less crowded, but it bears a superior leaving group, viz. 2 as opposed to the C 1 . S 0 . 0 C H 3 attached to the alternative electrophilic carbon. There can be n o question that the trichlorosulfone is an authentic chlorinolysis product since (i) both hydrolysis and alcoholysis of the sulfinate ester 5 furnish the dichlorosulfone 6, (ii) hydrolysis o f the sulfonyl chloride 2 furnishes 6, and (iii) one- to two-hour chlorinolvsis of simple sulfones like 6 affoids unchanged starting material (10).

W e were unaware of any examination of possible reactions between sulfinyl chlorides and molecular chlorine and were thus unable to judge whether the CS bond cleavage observed during the chlorinolysis of the sulfinyl chloride 4 was a typical or unusual result. Consequently, we have prepared a series of simple sulfinyl chlorides 7a --, 7c and subjected them to chlorinolysis in aprotic media.

The chlorinolysis of chloromethanesulfiny1 chloride3 70 in methylene chloride produced unchanged sulfinyl chloride quantitatively. A second run conducted in carbon tetrachloride showed no methylene chloride present in the product.

Chlorinolysis of methanesulfinyl chloride' 7b produced unchanged sulfinyl chloride along with a 13.5% yield of methanesulfonyl chloride, presumably arising from hydrolysis of the oxodichlorosulfonium cations by moisture present in the methylene chloride employed as solvent.

Both chloromethansulfinyl chloride 7a and methanesulfinyl chloride 7 b were produced free of the corresponding sulfonyl chlorides using our previously published method (1 I ) .

CAN. J . CHEM. VOL. 62. 1984

The phenethyl sulfinyl chloride 7c employed in our study was prepared by chlorinolysis of phenethyl thiolacetate following the procedure of Kee and Douglass ( 12). Hydrolysis of a sample of 7c prepared in this way showed it to contain ca. 20% phenethyl sulfonyl chloride. Chlorinolysis of phenethyl

I sulfinyl chloride 7c did not furnish any phenethyl chloride. The product was, in fact, ca. 50% 7c and ca. 50% phenethyl sulfonyl chloride.

These results indicate that the CS bond cleavage observed during the chlorinolysis of 4 is not a routine feature of sulfinyl chloride chlorinolyses.

Since our initial report of CS bond cleavage during the chlorinolyses of a-polychlorosulfoxides (13), we have been concerned about the probability that a nucleophile would be capable of attacking such severely hindered electrophilic carbon atoms. Our subsequent report (9) (see Scheme 2, Y = Ph) in which the substantially more crowded electrophilic carbon atoms in the sulfonium salts derived from a-sulfonyl-a-polychlorosulfoxides appeared to suffer nucleophilic attack, albeit more slowly, heightened our concern. In fact, on a number of occasions, referees of our papers have suggested an alternative mechanism for CS bond cleavage in these reactions (see Scheme 4). This mechanism would circumvent steric problems, although we have had serious reservations about the likelihood that the requisite ion pair formed in the cleavage step of Scheme 4 would actually form. In order to test this proposal

I I we have carried out the following reaction. I

I CH2CI2 [8] CH3S02 CC12.SO.Ph + CI2 I HCI - CH3SO2 CCI,

I

The absence of the dichlorosulfone, which would arise from proton capture by the carbanion pictured in Scheme 4, suggests that this mechanism is an unlikely one. Because the reaction pictured in eq. [8] is very slow (chlorination time 8 h), we have camed out a chlorination on 1,l-dichloro-2-thiapropane-2,2- dioxide.

SCHEME 4

The absence of dichlorosulfone in the product mixture (eq. [8]) cannot be rationalized by assuming that it was quantitatively converted to trichlorosulfone under the reaction conditions.

The results depicted in eq. [8] are of some interest. That reaction is the first example of an a-polychlorosulfoxide chlorinolysis in which attack at the a'-carbon is the major pathway. The absence of benzenesulfinyl or benzenesulfonyl chlorides in the product mixture implicates the dichlorosulfone-sulfinyI chloride as the intermediate leading to the trichlorosulfone. Despite our dissatisfaction with the Scheme 4 mechanism, the results from the chlorinolysis of the sulfinate ester 5, in our view, require a more complex mechanism than the simple picture presented in Scheme 2. The revised mechanism would apply to the cleavage steps in the chlorinolyses of all the a-sulfonyl systems we have studied (vide Schemes 2 and 3). At this stage, the most reasonable modification of the cleavage step mechanism would likely involve a complexing interaction between the incoming chloride ion and the a-sulfonyl group.

V ET AL. 613

Since we have recently initiated a program of theoretical calculations designed to clarify mechanistic details for the various steps of the Sulfohaloform reaction (see ref. 14, for example), we shall defer a more detailed proposal for cleavage step transition states for a-sulfonyl substituted systems until sup- porting calculations can be carried out.

In conclusion, we have prepared and chlorinated a- mercaptodimethyl sulfone which has established that the sulfenyl chloride 3a is transformed into 2 upon aqueous chlorinolysis, as we had proposed earlier (1). The role of Pummerer rearrangements in the transformations involved in the conversion 3a + 2 remains to be established. The chlorinolyses of both the sulfinyl chloride 4 and the sulfinate ester 5 have revealed unprecedented CS bond cleavage for these functional groups, indicating a need to revise the simple mechanism advanced previously for CS bond rupture during chlorinolysis of a-sulfonyl sulfoxides (9).


Details have been provided previously (10).

Preparation of CH3SCH2SAc A solution of thioacetic S-acid (0.739 g) in dry pyridine (25 mL)

was cooled and chloromethyl methyl sulfide (1.002 g) in carbon tetrachloride (2 mL) was added dropwise over 3 min. The reaction mixture was stirred at ambient temperature for 1 h. Methylene chloride (100 mL) was added and the resultant solution washed with 5% HC1 (100-mL aliquots) until the aqueous pH remained acidic. The organic layer was dried and concentrated and the residue distilled at reduced pressure, affording the sulfide-thiolacetate (0.544 g, bp 78-80"C/2.4 Torr); ir (CHCI,): 1695 cm-'; nrnr (CDCI,) 6: 4.13 (2H, s), 2.46 (3H, s), and 2.26 (3H, s); ms mle: 136 (M?, 35. I%), 61 (63.7%), and 43 (100%).

Preparation of CH3S02CH2SAc m-Chloroperoxybenzoic acid (85%, 3.145 g) was added to a cooled

solution of the sulfide-thiolacetate (1.002 g) in chloroform (30 mL). The reaction was allowed to reach ambient temperature while stirring overnight. Methylene chloride (170 mL) was added and the resultant solution washed with 1% NaOH (two 50-mL aliquots). The organic layer was dried and concentrated, affording clean sulfone-thiolacetate (1.20 g); ir (CHCI,): 1720, 1320, and I 1 10 cm-'; nrnr (CDCI,) 6: 4.50 (2H, s), 3.03 (3H, s), and 2.56 (3H, s); ms tnle: 168 (M?, 0.9%), 89 (13.6%), and 43 (100%).

Preparation of CH.qSOrCH2SH 3d The sulfone-disulfide 3c (0.200 g) (2) was dissolved in a solution

containing methylene chloride (10 mL), pyridine (0.1 mL), and benzenethiol (0.200 g). The reaction mixture was stirred at ambient temperature for 2 h and the solvent evaporated. The residue was chromatographed on silica gel (10 g) employing chloroform elution (5-mL fractions). Fractions 4 and 5 contained diphenyl disulfide and unreacted benzenethiol. Fractions 7-13 contained oily a-mercaptodimethyl sulfone 3d4 (0.078 g) which had ir (CHCI,): 2590, 1320, and 1125 cm-'; nrnr (CDCI,) 6: 3.83 (2H, d), 3.33 (3H, s), and 2.30 ( lH, t); ms m/e: 126 ( M I , 23.6%), 93 (24.7%), 81 (loo%), and 65 (62.5%).

Aqueous chlorinolysis of 3d Mercaptosulfone 3d (0.100 g) was dissolved in glacial acetic acid

(25 mL) and water (5 mL). C1, (ca. 200 mL/min) was bubbled into the reaction mixture for 0.5 h. Methylene chloride (I00 mL) and water (50 mL) were added and the layers separated. The organic layer was washed with 2.5% w/v sodium hydroxide solution (two 50-mL ali- quot~) , dried, and concentrated. The residue was the sulfone-sulfonyl

4 T h i ~ compound was too unstable for analysis, but its spectra provide unambiguous evidence for the structure.

chloride 2 (0.186 g) which was identical with authentic material ( I ) by ir, nmr, and tic.

Hydrolysis of 2 The dichlorosulfone-sulfonyl chloride (0.186 g) obtained from the

chlorinolysis of 3d (described above) was dissolved in water (I0 mL) and the reaction mixture refluxed for I h. Chloroform (200 mL) was added, and the mixture dried with MgS04 and filtered. The chloroform was evaporated, affording clean dichloromethyl methyl sulfone (0.072 g) which was identical to authentic material by ir, nmr, and mp (1).

Preparation of CH3SOZCC12 .SO. C14 The dichlorosulfone-sulfenate ester 3 f (2) (1.045 g) was dissolved

in methylene chloride (25 mL) and Clz (ca. 200 mL/min) bubbled into the reaction mixture for 0.5 h. The solvent was evaporated and the crude residue recrystallized from CCI,, affording pale yellow crystals of sulfone-sulfinyl chloride (0.637 g, mp 38-40°C). The sulfinyl chloride 4 had ir (CHCI,): 1350, 1 166, and 1 175 cm- ' ; A,,,,, (hex- anes):' 226 (E 3 488), 274 (E 377); nrnr (CDCI,) 6: 3.36 (s); ms mle: 79 (35.5%) and 63 (100%). Anal. calcd. for CzH3CI,03SZ: C 9.78, H 1.23; found: C 9.31, H 1.37.

Preparation of CH.3S02CC12.S0 OCH.< 5 The sulfone-sulfinyl chloride 4 (I .003 g) was dissolved in methanol

(25 mL) and the reaction mixture stirred at ambient temperature for 0.5 h. The solvent was evaporated, the residue dissolved in chloroform (5 mL), and the resultant mixture filtered. The chloroform was evaporated and the residue crystallized from methanol, affording clean 5 (0.820 g, mp 56-58°C). The product had ir (CHC13): 1345, 1200, and 1 150 cm- I; nrnr (CDCI,) 6: 3.33 (3H, s) and 4.10 (3H, s); ms m/e: 79 (100%) and 63 (27.8%). Anal. calcd. for C3H6CI2O4S2: C 14.94, H 2.51; found: C 14.86, H 2.59.

Hydrolysis of CH3SOZCClr.S0 - C 1 4 The sulfinyl chloride 4 (0.985 g) was added to distilled water

(10 mL) and the reaction mixture refluxed gently for 0.5 h. The reaction mixture was homogeneous by the time reflux began. The reaction mixture was cooled to room temperature and poured into chloroform (300 mL). The chloroform was dried (MgS04) and concentrated, affording the dichlorosulfone 6 (0.535 g). After recrystallization, the dichlorosulfone 6 was shown to be identical with authentic material by ir, nmr, mp, and mixture mp.

Chlorinolysis of CH3S02CClz - SO OCH.3 5 The sulfinate ester 5 (0.991 g) was dissolved in methylene chloride

(25 mL) and CIZ (ca. 200 mL/min) was bubbled into the solution for 1 h. The solvent was evaporated and the residue recrystallized from 95% ethanol, affording 1, l . l -trichloro-2-thiapropane-2,2-dioxide (0.464 g) which was identical with authentic material by nmr, ir, mp, and mixture mp.

Chlorinolysis of CH3S02CC12. SO. C14 The sulfinyl chloride 4 (1.000 g) was dissolved in methylene chlo-

ride (25 mL) and CI2 (ca. 200 mL/min) was bubbled into the reaction mixture for 2 h. The solvent was evaporated. The residue was recrystallized from 95% ethanol, affording 1,1,1 -trichloro-2-thiapropane-2,2-dioxide (0.202 g) which was identical with authentic material by ir, nmr, and ms. The mother liquor from the recrystallization contained 1,l-dichloro-2-thiapropane-2,2-dioxide (0.210 g) and residual trichlorosulfone (0.197 g).

Thus the sulfinyl chloride had been converted to the trichlorosulfone (50% yield) by the 2-hour chlorinolysis.

Preparation of PhCH2CHzSAc The mesylate of 2-phenyl ethanol (9.2278 g) and thioacetic S-acid

(3.517 g) were added to dry pyridine (100 mL) and the reaction mixture stirred at ambient temperature for 7 days.' Chloroform (200

5Compare with CH,-SOsC1, A,,, (hexane): 196 (E 6 320) and 289 (E 600) (1 5).

6~ run terminated after 3 days at room temperature afforded a mixture of thiolester (75%) and unchanged mesylate (25%).

614 CAN. J . CHEM. VOL. 62. 1984

mL) was added and the resultant mixture washed with 5% HCI (100-mL aliquots) until the aqueous pH remained acidic. The organic layer was dried (MgS04) and concentrated. The residue was rectified at reduced pressure, affording clean thiolester (5.096 g, bp 80-84"C/0.3 Torr). The product had ir (CHCI,): 1695 cm-'; nmr (CDCI,) 6: 7.26 (5H. s), 3.00 (4H, m), and 2.30 (3H, s); ms nl/e: 180 (M?, 3.8%), 104 (78.2%), 91 (36.9%). and 43 (100%). Anal. calcd. for Cl"HlzOS: C 66.62, H 6.70; found: C 66.83, H 6.74.

Preparation of PhCHzCHL. SO CI 7c C12 (ca. 200 mL/min) was bubbled into a solution of 2-phenethyl

thiolacetate (5.00 g) in acetic anhydride (2.83 g) for 0.5 h. The reaction temperature was maintained just above the freezing point with an acetone/Dry Ice bath as necessary. By the end of the reaction, the mixture had taken on a persistent orange color. The reaction mixture was concentrated in vacuo and the residue rectified, affording impure sulfinyl chloride (1.24 g, bp 128-130"C/0.5 Torr). The sulfinyl chloride7 had ir (CCI,): 1155 cm-'; nmr (CDCI,) 6: 7.30 (5H, s) and 3.45 (4H, m).

The purity of the sulfinyl chloride sample was established as follows. A sample of the sulfinyl chloride (1.0 g) was added to a solution of glacial acetic acid (25 mL) and water (5 mL) and the reaction mixture stirred at ambient temperature for 0.5 h. Water (35 mL) was added and the resultant mixture washed with chloroform (three 50-mL aliquots). The combined organic extracts were washed with 2.5% NaOH (50-mL aliquots) until the aqueous pH remained basic. The organic layer was dried (MgSO,) and concentrated. The residue was 2-phenethyl sulfonyl chloride (0.187 g) which was identical with authentic material by ir and nmr. Thus the original sulfinyl chloride sample was ca. 81% (by weight) sulfinyl chloride and 19% sulfonyl chloride.'

Preparation of CH3 SO CI 7b and CICHz. SO. CI 7a The sulfinyl chlorides 70 and 7b were prepared using our published

procedures (I I). The sulfinyl chlorides prepared in this way were not contaminated with the corresponding sulfonyl chlorides.

Chlorinol)~ses of 7a, 7b, 7c The appropriate sulfinyl chloride (I .O g) was dissolved in methy-

lene chl&ide-(25 mL) and CIz (ca. 200 momin) was bubbled into the reaction mixture for 2 h. The solvent was evaporated.

Chloromethane sulfinyl chloride 7a was recovered unchanged from the chlorinolysis.

Crude product from the chlorinolysis of 7c was subjected to hydrolysis in aqueous acetic acid as described under "Preparation of PhCHzCHz. SO. C17c". Phenethyl sulfinyl chloride 7c was converted into a mixture containing 7c (0.450 g) and phenethyl sulfonyl chloride (0.536 e ) .

~ethanesu l f in~ l chloride 7b was converted into a mixture of methanesulfinyl chloride (0.688 g) and methanesulfonyl chloride (0.158 g).

Chlorir~olysis of CHSO2CCIz .SO Ph Run 1 The dichlorosulfone-sulfoxide (0.5582 g) was dissolved in methyl-

ene chloride (50 mL). Clz (ca. 200 mL/min) and HCI (ca. 200 mL/min) were simultaneously bubbled into the reaction mixture for 8 h. The solvent was evaporated. The crude contained no

I 1,l-dichloro-2-thiapropane-2,2-dioxide as indicated by nmr. The

~ crude product was chromatographed on silica gel (45 g) employing carbon tetrachloride elution (thirty-one 50-mL fractions). Fractions 13-20 were combined and concentrated, afford~ng I, I , l -trichloro- 2-thiapropane-2,2-dioxide (0.0835 g) which was identical with authentic material by ir, nrnr, and mp. Further elution with chloroform (six 50-mL fractions) furnished a mixture of unchanged

-

7The ir indicated contaminating sulfonyl chloride was present. Moderate intensity bands were present at 1385 and 1170 cm-'.

"here is little or no hydrolysis of sulfonyl chlorides under the conditions employed. Such conditions permit the isolation of sulfonyl chlorides in high yields (16).

dichlorosulfone-sulfoxide (0. I91 g) and 1.1-dichloro-Zthiapropane- 2,2-dioxide (0.038 g)."he identity of the dichlorosulfone was confirmed by addition of authentic material to the mixture, which increased the relative intensity of the appropriate signals in the nrnr spectrum of the mixture.

Run 2 The dichlorosulfone-sulfoxide (0.5190 g) was dissolved in methy-

lene chloride (50 mL). CIZ (ca. 300 mL/min) and HCI (ca. 100 mL/min) were bubbled into the reaction mixture for 8 h. The reaction mixture was evaporated to ca. 20 mL. Gas chromatography carried out on the solution indicated the presence of chlorobenzene (peak intensity increased upon addition of authentic material). The solution was concentrated. Nuclear magnetic resonance indicated a 1 : 1 mixture of chlorobenzene (relative intensity of chlorobenzene signal increased upon addition of authentic material) and I , ] , 1 -trichloro-2-thiapropane-2,2-dioxide. Reflux of the crude in water (10 mL) for 1 h did not furnish any dichlorosulfone, indicating that the chlorinolysis had gone to completion. Product was isolated by pouring the aqueous mixture into methylene chloride (500 mL), drying (MgSO,), and concentrating the organic phase. The residue was recrystallized from methanol, affording 1,1,1 -trichloro-2-thiapropane-2Jdioxide (0.17 14 g).

Chlorino1)~sis of CH.3SOzCHCIZ The dichlorosulfone (0.4799 g) was dissolved in methylene chlo-

ride (50 mL). C12 (ca. 300 mL/min) was bubbled into the reaction mixture for 8 h and the solvent evaporated. The crystalline crude was a mixture of 1 ,I-dichloro-2-thiapropane-2,2-dioxide (86%) and 1,1,1 -trichloro-2-thiapropane-2,2-dioxide (14%). Identity of the trichlorosulfone was confirmed by the addition o f authentic material which increased the relative intensity of the appropriate signal in the nmr of the mixture.

Acknowledgements The authors are indebted to Dr. J. H. Kim for running the

mass spectra. W e are grateful to Dalhousie University a n d Mount Allison University for financial support in the form o f grants f rom their respective Research Development Funds.

1. W. R . HARDSTAFF, R. F. LANGLER, J . LEAHY, and M. J . NEW- MAN. Can. J . Chem. 53, 2664 (1975).

2. T. P. AHERN, R. F. LANGLER, and R. L. MCNEIL. Can. J . Chem. 58, 1996 (1980).

3. (a) W. R. HARDSTAFF and R. F. LANGLER. In Sulfur in organic and inorganic chemistry. Vol. 4. Edited by A. Senning. M. Dekker, Inc., New York. 1982. p. 229; (b) p. 230.

4. M. R. ALTAMURA, T. HASSELSTROM, and L. LONG, JR. J . Org. Chem. 28, 2438 (1963).

5. C. M. STIRLING. Int. J . Sulfur Chem. Part B , 6, 277 (1971). 6. H. KWART, E. N. GIVENS, and C. J . COLLINS. J . Am. Chem.

SOC. 91, 5532 (1969). 7. J. G. TRAYNHAM and A. W. FOSTER. J . Am. Chem. Soc. 93,

6216 (1971). 8. I. B. DOUGLASS and D. R. POOLE. J . Org. Chern. 22,536 (1957). 9. D. G. KAY, R. F. LANGLER, and J . E. TRENHOLM. Can. J . Chem.

57, 2185 (1979). 10. J . S. GROSSERT and R. F. LANGLER. Can. J . Chem. 55, 407

(1977). 11. J . S. GROSSERT, W. R. HARDSTAFF, and R. F. LANGLER. Can. I.

Chem. 55, 421 (1977). 12. M. L. KEE and I. B. DOUGLASS. Org. Prep. Proced. 2, 235

(1 970). 13. J . S. GROSSERT and R. F. LANGLER. Chem. Commun. 49 (1973). 14. J . L. GINSBURG and R. F. LANGLER. Can. J. Chem. 61, 589

(1983). 15. R. F. LANGLER. Ph.D. Thesis, Dalhousie University. 1975. 16. R. F. LANGLER. Can. J . Chem. 54, 498 (1976).

9The origin of the dichlorosulfone was very likely from hydrolysis of sulfinyl chloride 4 present in the crude.

The consequences of steric effects in the cleavage step of the sulfohaloform reaction

Dep(rrtmerrt ~$Cllctnistr?~, Doll~o~r.sie Utrioef-sity, HtrlV(i.v, N . S . , Crrtrotltt B3H 453

Received Febluary 16, 1979

DENIS GEORGE KAY, RICHARD FRANCIS LANGLER, and JUNE ELLEN TRENHOLM. Can. J. Chem. 57.2185 (1979).

The pathway for the aqueous chlorinolysis of a series of p-sulfonyl-sulfides is elucidated and the SN2 cleavage step examined. Steric effects in the cleavage of the a-polychloro-oxochlorosulfonium chloride intermediates are held to be responsible for the suppression of the established nucleophilic competition between water molecules and chloride ions with the result that all cleavage products arise from nucleophilic attack by chloride ions. This report details the second known example of successful SN2 displacement on a carbon atom ci to a sulfonyl group.

DENIS GEORGE KAY, RICHARD FRANCIS LANGLER et JUNE ELLEN TRENHOLM. Can. .I. Chem. 57,2185 (1979).

On a etudit les chemins reactionnels impliques lors de la scission d'une serie de p-sulfonyl- sulfures sous I'influence du chlore et on a examine l'etape de clivage SN2. On croit que des effets steriques dans le clivage d'interrnkdiaires chlorure d'a-polychloro-0x0-chlorosulfoniurn sont responsables de la suppression de la competition nucleophile bien etablie entre les molecules d'eau et les ions chlorures qui donne lieu au fait que tous les produits de clivages provien- nent d'une attaque nucleophile par les ions chlorures. Dans ce travail, on donne les dttails du deuxieme exemple d'une substitution SN2 reussie sur un atome de carbone en a d'un groupe sulfonyle.


Introduction As a part of our program to study the chlorination

of sulfur compounds (1-lo), we have recently published details which support a generalized pathway for the conversion of dialkyl sulfides into sulfonyl chlorides (5). The generalized pathway was called the sulfohaloform reaction (vide Scheme 1).

CIJH20 R. S. CH,R' - R. S. CHCIR' (R = CH2R1) HOAc

I

SCHEME 1. The sulfohaloform reaction

The intermediate cc-polychloro-oxochlorosulfonium chloride salts were shown (5) to undergo three competing processes, viz. (i) cleavage by nucleophilic attack of water molecules on the chlorine-bearing carbon cc to the sulfoniuln sulfur atom, (ii) cleavage by nucleophilic attack on the same carbon atom by chloride ions, and (iii) Pummerer rearrangement to

'To whom all correspondence should be addressed.

TABLE 1. * Relative percentages of oxochlorosulfonium chloride cleavage by

competing nucleophiles

Nucleophile (%) Sulfoxide precursors H z 0 CI -

'Data calculated from previously published results ( 5 ) .

furnish another a-polychlorosulfoxide. These competing processes are presented for trichloronlethyl methyl sulfoxide in Scheine 2.

low charts were detailed (5) defining the balance between the competing processes when the di- and trichlorodimethyl sulfoxides were converted into methane and chloromethane sulfonyl chlorides. Table 1 presents the relative percentages of the cleavage products from the oxochlorosulfonium chloride salts2 (derived from the sulfoxides listed) induced by nucleophilic attack of water molecules and chloride ions.

'Structure A, Scheme 2 depicts the structure of an oxochlorosulfonium chloride salt.

0008-40421791 162 185-06$0 1 .OO/O 01979 National Research Council of CanadaIConseil national de recherches du Canada

C A N . J . CHEM. VOL. 57, 1979

t

C 0 2 + HCI SCHEME 2

From the data in Table 1, we have tentatively inferred that increasing incorporation of bulky chlorine atoms in the oxochlorosulfonium chloride intermediates hinders nucleophilic attack by water molecules substantially more than nucleophilic attack by chloride ions. I11 order t o test this point experi- mentally, we have undertaken the preparation of systems which would (i) provide even more crowded a-polychloro-oxochlorosulfonium chloride intermediates and (ii) structurally preclude complicating Pummerer rearrangements. We have chosen to meet these objectives with substrates of the type shown below:

0

For some time, it was believed that leaving groups attached to a sulfonyl-bearing carbon atom could not be displaced (11-19). The lack of reactivity for these systems was ascribed to "the repulsion of the nucleophilic species by the negative field of the sulfonyl oxygen atoms" (17). An examination of models led to the conclusion that a mesyl group3 would have "only a small steric effect, unless it is assumed that the partial negative charge on the oxygen atoms would greatly extend their effective radius" (1 5).

3Mesyl is an abbreviation of methylsulfonyl.

Later, the surprising report of Robson et al. (20) documented, without comment, the successful dis- placeinent of the chlorine atom of chloroinethyl methyl sulfone by mercaptide anions. This reaction was subsequently exploited for synthetic purposes (8, 21) and formed the basis for a more extensive investigation of nucleophilic displacen~ents involving chlorinated sulfones and mercaptide anions (3). Furthermore, an examination of space-filling models convinced us that a mesyl group is very similar in volume to a tertiary butyl group and that the analogy of the mesylmethyl group with the neopentyl group, first suggested and discarded by Bordwell (15), is a very good one. I t appeared, a t least tentatively, that the assumption of nucleophilic repulsion by sulfonyl oxygen atoms might be unnecessary to account for the known chemistry. In this connection, it is interesting t o note that di-tert-butyl-methanesulfinyl chloride could not be converted t o the corresponding sulfonyl chloride, even under forcing conditions (22). Such an observation might well be a consequence of the crowding necessary to introduce a bulky chlorosulfonyl group into an already crowded molecule.

Results and Discussion

Our previous study (5) established two modes of behaviour for chlorosulfonium chloride salts gener- ated in aqueous media, i.e., ( i ) dialkyl chlorosulfonium chloride salts are very resistant t o hydrolysis

KAY ET AL.

TABLE 2. Chlorinolysis of 0.1 g CH3S02CH2SPh (la)

Volume of CIz/HzO' CH3S02CH2SPh CH3S02CH2SOPh CH3SO2CHC1SOPh CH3SO2CCI2SOPh

(mL) (7,) (%I (%I (%I

*H20 was saturated with CI2 at ambient temperature.

and react essentially exclusively by Pummerer rearrangement ( Ib ) and ( i i ) a-chlorodialkyl chlorosulfonium chloride salts undergo quantitative hydrolysis with essentially no Pummerer rearrangement as shown in Scheine 1 .

A priori, either reaction could be advanced as the first step in the pathway for the aqueous chlorinolyses of the sulfone-sulfides la-6a, since ( i ) the sulfonyl methyl groups are substantially more electron withdrawing than a chloromethyl group4 and therefore should enhance the electrophilicity of the sulfonium sulfur atom, thus facilitating hydrolysis of the chlorosulfonium chloride salts derived from la-6a, and (i i) the sulfonyl methyl groups greatly enhance the acidity of the protons adjacent to the sulfonium sulfur atom and consequently might be expected to enhance the rate of the elimination step by which the sulfenium ion (Pummerer intermediate ( Ib ) ) forms.

The results of a series of controlled chlorinolyses of l a are presented in Table 2. These results establish that the first formed chlorosulfonium chloride salt undergoes hydrolysis preferentially and that further products arise through the intermediacy of the unchlorinated sulfone-sulfoxide. Larger amounts of chlorine furnished the corresponding a,a-dichlorosulfoxide l b . Scheme 3 presents the synthesis and pathway for the reactions which provided the dichlorosulfone-sulfoxides lb-66. The structure of l b was confirmed by converting a sample into the corresponding dichlorodisulfone ( Id ) . The disulfone Id was shown to be identical to a sample prepared by oxidation of the dichlorosulfone-sulfide l c .

Exhaustive chlorinolysis of the dichlorosulfone- sulfoxides lb-66 furnished an equimolar mixture of the appropriate trichloromethyl sulfone and sulfonyl chloride shown in Table 3. Nucleophilic attack by water molecules at the carbon atom of the dichloro- methylene group in the intermediate oxochlorosulfonium chloride would result in the formation of an intermediate hydroxydichloromethy1 sulfone. Such a compound would be expected to eliminate

4Pauling electronegativities: X , (CICHZ) = 2.47, X, (CH3SO2CHZ) = 2.85, and X, (PhSOzCHZ) = 2.75 (lb, 23).

EtONa R. SOI,CHZCI + HSR' - R . SO2, CHZSR1

EtOH lrr-6n

R. S02CCIf SO. R' 2 R = CH,, R' = pClPh

lb-6b 3 R= CH,, R' = pCH,Ph 4 R = Ph,R'= Ph 5 R = Ph, R' = pClPh 6 R = Ph, R' = pCH,Ph

HCl, hydrolyze, decarboxylate, and react with molecular chlorine to furnish the appropriate sulfonyl chloride, e.g., this sequence in the case of l b would result in the formation of methanesulfonyl chloride. In no case was there any detectable sulfone-derived sulfonyl chloride present in the product mixture. Consequently the only nucleophiles to attack at the central carbon atom in the oxochlorosulfonium chlorides derived from lb-66 were chloride ions. Scheme 4 presents a rationale for the formation of the observed products.

TABLE 3. Yields* of sulfones and sulfonyl chlorides from exhaustive aqueous chlorinolyses of lb-66

Products

RSOZCI R'SOZCCI3 Substrate (% yield) (% yield)

l b R = Ph (80) R' = CH3 (78) 26 R = pC1-Ph (80) R' = CH3 (80) 36 R = pCH3Ph (75) R' = CH3 (83) 46 R = Ph (86) R' = Ph (90) 56 R = pClPh (72) R' = Ph (78) 66 R = pCH3Ph (83) R ' = P h (81)

*For mechanism see Scheme 4.

2188 CAN. J . CHEM. VOL. 57 . 1979

R SO: CCIZ SO. R' CIZIH,O lh-611

CI

R ' SO. CI + R. SO, CCI,

We have previously observed (5) a difference in the overall rate of reaction for the aqueous chlorinolysis of chloromethyl phenyl sulfide (product: benzenesulfonyl chloride; relative rate: 1) and the aqueous chlorinolysis of chloromethyl methyl sulfide (product: methanesulfonyl chloride, relative rate: 6.5). The slower reaction for the phenyl sulfide was attributed to an electron-donating effect from the phenyl group which would reduce the electrophilicity of the sulfonium sulfur atom in the oxochlorosulfonium chloride intermediate. However, a comparison of the overall rate of the chlorinolysis of the mesyl dichlorosulfoxide l b , and the rate of chlorinolysis of phenyl trichloromethyl sulfoxide (5) indicates that l b reacts some 22.3 times slower. This difference cannot be attributed to an electronic effect originating with the phenyl group. One might then examine the possible role of the mesyl group in terms of the effect of sulfonyl oxygen atoms on approaching nucleophiles, as outlined earlier. Clearly, if the sulfonyl oxygen atoms offer a 'negative field' they would repel incoming chloride ions much more than incoming water molecules. Since cleavage by nucleophilic attack a t the central carbon atom occurs exclusively by the agency of chloride ions we conclude that the effect of the mesyl group is not a special electronic effect but rather a more familiar steric effect.

In order to determine the relative sizes of chloride ions and water molecules, we have made accurate scaled drawings of each species. The somewhat remarkable conclusion was that there is essentially no difference in the cross-sectional area of a chloride ion and a water molecule. The most likely reason for the superior nucleophilicity of chloride ions lies with the greater polarizability of these nucleophiles. An interesting alternative or additional consideration arises from an overview of SN2 displacements of leaving groups a to sulfonyl groups.

The successful displacement of the sulfinyl chloride group by chloride ions represents the second known case of an S,2 displacement a to a sulfonyl group. Both nucleophiles, viz. chloride ions and mercaptide ions, which have been effective in accomplishing these displacements involve third-row nucleophiles. An intriguing possibility is that of a complexing interaction between these nucleophiles and the adjacent sulfonyl sulfur atom. We have recently proposed such an interaction in order to rationalize a novel thiolester hydrolysis (la).

The chlorinolyses of the sulfone-sulfoxides 16-3b resulted in the formation of a minor product (ca. 5%) which gave rise to a singlet in the nmr of the crude a t 6 3.50. Thin layer chromatography, visualized with NaI-acetone (7), showed the presence of a compound at R, 0.50. These properties are in accord with the presence of CH3S02CC12S02C1 (7) which we have characterized previously (8). Furthermore, column chromatography furnished dichloromethyl methyl sulfone which was absent in the crude reaction mixture.

Dichloromethyl methyl sulfone is the known hydrolysis product obtained from CH3S02CC12- S02Cl (3, 8). Chromatography has been shown to furnish substantial hydrolysis of a close structural relative of 7 (7).

It appears that the severe crowding in the oxochlorosulfonium chloride salts derived from lb-3b has succeeded in diverting some nucleophilic attack to the phenyl ring. Attack at the less crowded centre would presumably be carried out by water molecules. A rationale for this process is presented in Scheme 5. The preceding account details the first evidence that nucleophilic attack can be diverted from the chlorine- bearing carbon atom in the cleavage of a-polychloro- oxochlorosulfonium chlorides.

A consequence of the results reported in this paper is that methylsulfonyl groups have potential application in the design of molecules intended for the study of steric effects on chemical reactions. A feature worth noting is the great facility with which they may be introduced into substrates, a feature which they do not share with the ubiquitous tertiary butyl group. A potentially useful property of these groups is their destablization of nearby carbocationic centres (24) which would permit studies of SN2 cleavages without facilitating SN1 processes.

In conclusion, a study of sulfonyl substituted a-polychlorosulfoxide chlorinations has shown that the corresponding oxochlorosulfonium chlorides undergo cleavage in which steric factors favor nucleophilic attack by chloride ions and disfavor nucleophilic attack by water molecules. The results obtained are inconsistent with the view that the adjacent sulfonyl groups offer a 'negative field'

KAY ET AL. 2189

C H , SO, CCI,- S O ~ X

16 X = H 26 X = C1 311 X = CH,

C H , SOz CCIy SO. CI + HO [ ex]

which repels nucleophiles. Finally, the substantial crowding achieved in the transition state has shifted a small amount of the nucleophilic attack to the less crowded carbon attached to the sulfonium sulfur atom.

Experimental Getzero1

Their spectra were recorded on a Perkin Elmer 237B grating spectrophotometer. The nmr spectra were obtained on a Varian T-60 instrument using TMS as the internal standard. The mass spectra were recorded on a Dupont-CEC model 21-104 mass spectrometer. The samples were directly introduced using an all glass probe and the spectra run at 30 eV with a source temperature of 150°C. Melting points were determined on a Fisher-Johns melting point apparatus and are uncorrected.

Preparation of Suljbne-sulfides la-6a Sodium metal (1 equiv.) was dissolved in absolute ethanol

(100 mL) and the appropriate mercaptan (1 equiv.) added. Chloromethyl phenyl sulfone (25) or chloromethyl methyl sulfone (26) (10 g) was added and the reaction mixture refluxed for 24 h. Water (100 mL) was added and the resultant mixture was washed with chloroform (3 x 100 mL aliquots). The organic layers were combined, dried (MgS04), filtered, concentrated, and the residue recrystallized from 95% ethanol.

CH3S02CH2SPh l a (9.413 g, mp 4749°C); ir (CHCI,): 1320 and 1145 cm-'; nrnr (CDCI,) 6: 7.36 (5H, m), 4.23 (2H, s), and 2.93 (3H, s); ms tn/e: 202 ( M f , 4.7%), 123 (86%), and 45 (100%).

p-C1PhSCH2SO2CH3 20 (15.88 g, rnp 105-106°C); ir (CHCI,): 1320 and 1145cm-'; nmr (CDCI,) 6: 7.43 (4H, pseudo-quartet), 4.17 (2H, s), and 2.97 (3H, s); ms tnle: 238 (1.8%), 236 (M+, 5.773159 (33.379157 (100%),and 45 (80%).

p-CH3PhSCH2S02CH3 30 (14.67 g, mp 63.5-65°C); ir (CHCI,): 1320 and 1140 cm-'; nmr (CDCI,) 6: 7.37 (4H, pseudo-quartet), 4.20 (2H, s), 2.90 (3H, s), and 2.33 (3H, s); ms mle: 216 ( M t , 10.3%), 137 (loo%), and 45 (41.5%).

PhSO,CH,SPh 40 (1 1 .OO g, mp 56-58°C); ir (CHCI,): 1320 and 1140 cm- ' ; nmr (CDCI,) 6: 7.66 (lOH, m) and 4.40 (2H, s); ms tn/e: 264 ( M f , 7.3%), 123 (loo%), and 45 (30%).

p-C1PhSCH2S02Ph 5a (1 1.88 g, mp 67-69°C); ir (CHCI,) : 1320 and 1145 cm-'; nrnr (CDCI,) 6: 7.57 (9H, m) and 4.30 (2H, s); ms m/e: 300 (2.273, 298 ( M t , 6.673, 159 (33.373, 157 (loo%), and 45 (40%).

p-CH3PhSCH2S02Ph 60 (1 I .10 g, mp 8345°C); ir (CHCI,): 1320 and 1145 cm-'; nrnr (CDCI,) 6 : 7.40 (9H, m), 4.30 (2H, s), and 2.26 (3H, s); rns m/e: 141 (58%), 91 (33%), and 77 (100%).

Prepmation of CH3S02CCI,SPh (Ic) The sulfone-sulfide l a (1.000 g) was dissolved in carbon

tetrachloride (20 mL) and C12 (ca. 200 mL/min) was bubbled into the solution for 20 min. The solvent was evaporated and the residue recrystallized from 95% ethanol affording l c (1.176 g, rnp 53-54°C); ir (CHCI,): 1320 and 1145 cm-I ; nmr (CDCI,) 6: 7.66 (5H, m) and 3.50 (3H, s); ms tn/e: 195 (14%), 193 (69%), 191 (loo%), 109 (34x1, and 77 (44%).

Preparation of CH3S02 CC12S02P/1 (Id) The dichlorosulfone-sulfide l c (0.5002 g) was oxidized with

chromium trioxide in glacial acetic acid in standard fashion (3). The crude dichlorodisulfone was recrystallized from 95% ethanol (0.276 g, mp 102-105°C); ir: 1355 and 1152cm-'; nmr (CDCI,) 6: 7.90 (5H, m) and 3.53 (3H, s); ms m/e: 141 (7373, 125 (41%), and 77 (100%).

Preparation of Dichlorosulfone-s~rlfoxirles (Ib-6b) The desired sulfone-sulfide (10-60) (5.00 g) was added to a

solution of glacial acetic acid (25 mL) and water (5 mL). C1, (ca. 200 mL/min) was bubbled into the reaction mixture for 0.5 h. During the chlorination the product precipitates from solution. Upon completion of the chlorination water (50 mL) and methylene chloride (100 mL) were added. The layers were separated and the organic layer washed with 2.5% w/v NaOH (2 x 50 mL aliquots), dried (MgSO,), filtered, and the solvent evaporated. The residue was recrystallized from 95% ethanol affording the following compounds.

CH3S02CC12~S0.Ph 16 (5.284 g, mp 149-151°C); ir (CHCI,): 1345, 1150, and lO8Ocm-'; nmr (CDCI,) 6: 7.77 (5H, m) and 3.46 (3H, s); ms tn/e: 290 (0.1%), 288 (0.6%), 286 ( M t , I%), 125 (loo%), 109 (3973, and 77 (43%). Anal. calcd. for C8H8CI20,S2: C 33.45, H 2.80; found: C 33.07, H 2.91.

p-ClPhS(0)CC12S02CH3 26 (5.353 g, mp 8486°C); ir (CHCI,): 1340, 1145, and 1080 cm-' ; nmr (CDCI,) 6: 7.73 (4H, pseudo-quartet) and 3.50 (3H, s); ms nrle: 229 (2.2%), 227 (5.773, 225 (5.7%), 161 (33.373, and 159 (100%). Atiul. calcd. for CRH7ClaOaSz: C29.87. H 2.19; found: C29.95, . . -

H 2.15. p-CH,PhS(O)CCI,SO,CH, 36 (5.150 g, mp 145-147°C); ir

(CHCI,): 1345, 1150, and 1085 cm- ' ; nrnr (CDC13) 6: 7.73 (4H, pseudo-quartet), 3.50 (3H, s), and 2.53 (3H, s); ms m/e: 139 (loo%), 91 (27.5%), and 45 (12.5%). Anal. calcd. for CeH10CIZ03S2: C 35.88, H 3.34; found: C 35.83, H 3.14.

PhSO2CCI2,SO.Ph4b (4.894 g, mp 134136°C); ir (CHCI,): 1350, 1150, and 1 0 9 0 ~ m - ~ ; nmr (CDCI,) 6: 7.80 (m); ms tnje: 141 (36%), 125 (64%), 109 (48.6%), and 77 (100%). Anal. calcd. for C13HIOC1203S2: C44.70, H 2.88; found: C44.82, H 2.57.

p-CiPhS(O)CCI2SO2Ph 5b (3.8708, mp 115-117°C); ir (CHCI,): 1350, 1150, and 1095 cm-'; nrnr (CDCI,) 6: 7.83 (m); ms t~i/e: 161 (33.373 159 (loo%), 141 (43.6%), and 77 (65.9%). Anal. calcd. for Cl3H9CI3O3S2: C40.69, H 2.36; found: C 40.47, H 2.42.

p-CH3PhS(0)CC1,S02Ph 6b (4.563 g, mp 140-141°C); ir (CHCI,): 1350, 1150, and 1095 cm-'; nmr (CDCI,) 6: 7.70

2 190 CAN. J . CHEM.

(9H, m) and 2.46 (3H, s); ms m/e: 139 (loo%), 91 (16.6%), and 77 (26.8%). Anal. calcd. for Cl4Hl2ClZO3S2: C 46.28, H 3.32; found: C 46.01 and H 3.49.

Preparation of PII~SO~CH,SO,CH~ l e The sulfone-sulfide l a (1.002 g) was dissolved in a solution

of 30% H 2 0 z (0.568 g) in dioxane (25 mL). The reaction mixture was refluxed for 0.75 h. The solvent was evaporated and the residue recrystallized from 95% ethanol, (0.815 g, mp 88-90°C); ir (CHCI3): 1320, 1140, and 1045 cm-'; nmr (CDC13)S:7.60(5H,s),4.20(1H,d,J= 3Hz),4.13 ( lH ,d , J = 3 Hz) (26), and 3.23 (3H, s); ms tnle: 218 ( M i , 10.9%), 125 (loo%), 109 (23.1%), and 77 (32.9%). At~rrl. calcd. for C8H1003S3: C 44.01, H 4.61 ; found: C 43.89, H 4.21.

Cot~rrolled Aqrreolrs Cl~lorit~ol~~sis of l a A series of chlorinolyses of l o were conducted and the

results are tabulated in Table 2. Details below are provided for the run from which products were isolated.

The sulfone-sulfide l a (0.100 g) was dissolved in glacial acetic acid (75 mL) and distilled water (9 mL). Water (9 mL) which had been saturated with CIZ at ambient temperature was added and the reaction mixture stirred at room temperature for 0.5 h. Water (150 mL) was added and the reaction mixture washed with chloroform (300 mL). The organic layer was washed with 2.5% w/v NaOH (3 x 100 mL aliquots), dried, and concentrated. The residue showed four spots on analytical tlc (chloroform development). The nmr of the crude indicated the presence of l a (21%), the corresponding sulfone

0 /

sulfoxide (le) (31%), CH3S02CHC1SPh (2173, and l b (26%). The mixture was run on preparative tlc, developed with CHCI3-Et20 (1 :I). The band at R, 0.27 was scraped and washed with CHCI, (60 mL) affording l e which was identical with authentic material by nmr, ir, and tlc. The band at R, 0.57 was handled in the same way and furnished a mixture of l a and another compound. The identity of l a was confirmed by tlc and addition of authentic material which caused the expected change in the appropriate signals in the nmr of the mixture. Subtraction of the signals due to l o from the nmr of the mixture left the spectrum 6 : 7.50 (5H, m), 5.17 (IH, s), and 3.23 (3H, s). On this basis the second compound in the mixture was assigned the monochlorosulfone-sulfoxide structure shown above. The band at R, 0.81 was processed as described above, and afforded l b which was identical with authentic material by nmr, ir, and tlc.

Oxidation of l b The dichlorosulfone-sulfoxide l b (0.500 g) was oxidized to

the dichlorodisulfone I d in the same way described for the oxidation of lc. After recrystallization, the disulfone (0.350 g) was shown to be identical to authentic disulfone by ir, nmr, mp, and mixture mp.

Exl~austive Clllorit~ation of lb-6b Exhaustive chlorinations of the dichlorosulfone-sulfoxides

lb-6b were carried out as illustrated by the details provided below for the reaction on 2b. Results for these systems appear in Table 3.

The sulfone-sulfoxide 2b (0.500 g) was dissolved in glacial acetic acid (75 mL) and water (18 mL) added. CI, (ca. 200 mL/min) was bubbled into the reaction mixture for 8 h. Water (150 mL) was added and the resultant mixture washed with methylene chloride (3 x 100 mL aliquots). The combined organic layers were washed with 2.5% w/v NaOH (3 x 100 mL aliquots). The organic layer was dried and concentrated.

The residue was chromatographed on silica gel (50 g) employing carbon tetrachloride elution (50 mL aliquots). Fractions 6 9 were combined and concentrated affording

VOL. 57, 1979

p-chlorobenzenesulfonyl chloride (0.262 g) which was identical to authentic material by ir, nmr, ms, and tlc. Fractions 40-60 were combined and concentrated furnishing trichloromethyl methyl sulfone (0.245 g) which was identical to authentic material (27). Fraction 95 contained dichloromethyl methyl sulfone (0.015 g) which was identical to authentic material by ir, nmr, and mp (27).

Acknowledgements The authors are indebted to Dr. J. H. Kim for

running the mass spectra. We are grateful to Dal- housie University for financial support in the form of a grant from the Research Development Fund.

1. ((I) H. 0 . FONG. W. R. HARDSTAFF, D. G. KAY. R. F. L,INGLER, R . H. MORSL. and D. N . SANDOVAL. Can. J. Chem. 57. 1206 (1979); (h ) T. P. AHERN. D. G. KAY. and R. F. LANGLLR. Can. J. Chem. 56.2422 (1978).

2. R. F. LANGLER, 2 . A. MARINI. and J. A. PINCOCK. Can. J. Chem. 56.903 (1978).

3. R. F. LANGLER iind J. A. PINCOCK. Can. J. Chem. 55,2316 (1977).

4. J . S . GROSSERT. W. R. HARDSTAFF, and R. F. LANGLER. Can. J . Chem. 55,421 (1977).

5. J. S. GROSSEK.~ iind R. F. LANGLER. Can. J. Chem. 55, 407 (1977).

6. R. F. LANGLER. Can. J. Chem. 54,498 (1976). 7. J. R. JARDINE iind R. F. LANGLER. J. Chromatogr. 116,211

(1976). 8. W. R. HARDSTAFF, R. F . LANGLER, J. LEAHY, and M. J.

NEWCIAN. Can. J. Chem. 53,2664 (1975). 9. J . S. GROSSERT, W. R. HAKDS.~AFF, and R. F. LANGLER.

Chem. Commun. 50(1973). 10. J. S. GROSSERT i~nd R. F. LANGLEK. Chem. Commun. 49

(1973). 1 I. F. RASCHIG ilnd W. PRZHL. Justus Liebigs Ann. Chem. 448,

307 (1926). 12. T. THOMSON i~nd T. S. STEVENS. J . Chem. Soc. 69 ( 1932). 13. W. M. ~ I E G L E R and R. CONNOR. J. Am. Chem. SOC. 62.

2596 (1940). 14. T . B. JOHNSON and I. B. DOUGLASS. J. Am. Chem. Soc. 63,

1571 (1941). 15. F. G. B O R D W E L L ~ ~ ~ G. D. COOPER. J. Am. Chem. Soc. 73,

5184(1951). 16. F. G. BORDWELL and W. T. BRANNEN. J. Am. Chem. Soc.

86,4645 ( 1964). 17. L. A. PAQUETTE. J. Am. Chem. Soc. 86.4085 (1964). 18. F. G. BORDWELL and B. JARVIS. J. O g . Chem. 33, 1182

(1968). 19. M. CINQUINI, D. LANDINI, and A . MAIA. Chem. Commun.

734 (1972). 20. P. ROBSON, P. SPEAKMAN, iind D. STEWART. J.Chem. Soc.

C, 2180(1968). 21. W. G. PHILLIPS and K. W. RATTS. J. Org. Chem. 36. 3145

(1971). 22. J. BUTLER and R. M. KELLOGG. J. Org. Chem. 42, 973 -

(1977). 23. J. E. HUHEEY. J. Phys. Chem. 69. 3284 (1962): 70. 2086

( 1966). 24. T. DURST and F. DE REINACH-HIRTZBACH. Tetrahedron

Lett. 3677 (1976). 25. P. P. DAVIS, J. S. GROSSERT, R. F. LANGLER, and W. S.

MANTLE. Org. Mass Spectrom. 12.659 (1977). 26. W. R. HARDSTAFF and R. F. LANGLER. 01.g. Mass Spec-

trom. 10,215 (1975). 27. W. E. TRUCE, G. H. BIRUM, and E. T. MCBEE. J. Am.

Chem. Soc. 74,3594 (1952).

The sulfohaloform reaction revisited and revised

JAMES CLAYTON BAUM, WILLIAM RAYNE HARDSTAFF, RICHARD FRANCIS LANGLER,' A N D ANTHONY MAKKINJE Departtnent qf Chemistnj, Florida Institute of Technologj, Melbourtle, FL 32901, U.S.A.

Received November 20, 1983

JAMES CLAYTON BAUM, WILLIAM RAYNE HARDSTAFF, RICHARD FRANCIS LANGLER, and ANTHONY MAKKINJE. Can. J. Chem. 62, 1687 (1984).

A study of the aqueous chlorinolyses of a series of benzylic dithioacetals along with related a-chlorobenzylic sulfides is reported. These results require a modification of our previously proposed sulfohaloform reaction, so that thionium ion intermediates which have at least one alkyl group on sp2 carbon follow a different pathway.

JAMES CLAYTON BAUM, WILLIAM RAYNE HARDSTAFF, RICHARD FRANCIS LANGLER et ANTHONY MAKKINJE. Can. J. Chem. 62, 1687 (1984).

On rapporte une Ctude sur la chloronolyse, en milieu aqueux, d'une serie de dithioacktals benzyliques et des sulfures a-chlorobenzyliques apparentCs. Pour expliquer ces rCsultats, i l faut modifier le micanisme de reaction sulfohaloformique que nous avons proposi antkrieurement de facon B ce que les ions thionium intermediaires qui portent au moins un groupe alkyle sur le carbone sp2 suivent une voie diffkrente.


Introduction C1 Some time ago, we published an examination of the pathway

followed by dialkyl sulfides upon chlorinolysis in aqueous acetic acid ( I ) . The study involved a detailed examination of sulfides and led to a proposed general pathway which we called the sulfohaloform reaction. W e have subsequently carried out studies on the regiochemistry of the first step in aprotic media (2, 3) as well as an examination of steric effects in the cleavage step (4) in aqueous acetic acid.

The first step in the sulfohaloform pathway is believed to proceed as shown in Scheme 1 . The proposed intermediacy of a-chloro-chlorosulfonium cations (derived from a-chlorosulfides) in the sulfohaloform reaction rested on the following evidence: the chlorinolysis of the corresponding chlorine-free sulfoxides furnished different products from those obtained by chlorinolysis of the chlorine-free sulfides, thus ruling out sulfoxides as the first formed intermediates. The disturbing feature of the original proposal is the apparent inability of the thionium ion2 intermediates, formed in the second step, to undergo hydrolysis.

W e have subsequently developed benzylic sulfides as precursors for sulfonyl chlorides (8). While we did not establish whether aqueous chlorinolysis of benzylic sulfides proceeds by SN1 dissociation of the intermediate chlorosulfonium cations or by the intermediacy of the corresponding sulfoxides with unimolecular dissociation of the corresponding oxochlorosulfonium cations, we did demonstrate that these reactions proceed without Pummerer rearrangement (see Scheme 1 ). W e decided to generate benzylic thioniums ions, A, in order to determine whether they have any tendency to hydrolyze during exhaustive

+ RSCH2Cl t R.S=CH2 + HCI + Cl-

aqueous chlorinolyses. Such species, if hydrolyzed, would give rise to a-hydroxy sulfides which could dissociate to furnish phenylmethanethiol which would be transformed into phenylmethanesulfonyl chloride in aqueous acetic acid saturated with C12. On the other hand, if they undergo exclusive nucleophilic attack by chloride ions, the intermediate a-chlorosulfide would be transformed into the corresponding a-chlorosulfonyl chloride and benzyl chloride (8).

Simple alkyl benzylic sulfides are ruled out as precursors since ( i ) they appear to undergo dissociation into sulfenyl chlorides and benzyl cations after chlorosulfonium cation formation (8), and (ii) any thionium ion intermediates would form by abstraction of a benzylic proton rather than abstraction of a proton from the alkylated a-carbon (2, 3).

T o circumvent these problems we have decided to employ some dithioacetals, B, as precursors. Such substrates are

I + /R1 R2

PhCH2S=C B 'R2

A known to cleave pursuant to chlorosulfonium cation formation (9). The corresponding S-hydroxysulfonium sulfides are also known to dissociate in a parallel process (10). The expected ' Author to whom correspondence should be addressed. mechanism for thionium ion formation is shown in Scheme 2. ' Durst et a / . have called R . SO CHR an oxosulfenium ion 15). We . .

have called RSCHR a sulfenium ion (6) while Trost et a / . call it a Results and discussion thionium ion (7). A referee of this paper has pointed out that the term sulfenium ion has also been applied to RS'. To avoid confusion we T o begin our study of the simplest system, we have prepared shall refer to the first two species as oxothionium and thionium ions and chlorinated benzyl chloromethyl sulfide, which gave re- respectively. sults consistent with our previous report (8):

CAN. I. CHEM. VOL. 62, 1984

Volume of Volume of Volume of Clz/H20" Cl2/HOAcT HOAC (PhCH2S)I (PhCH2S)>CHCH1 PhCHrSOrCl PhCH2CI PhCH,OAc

(mL) (mL) (mL) (%I (%I (%I

10 - 50 8.8 69.2 - - -

10 25 25 10.1 17.8 30.9 18.0 20.6 10 50 - - - 52.0 24.5 26.5

" H 2 0 was saturated with CI, at ambient temperature. t HOAc was saturated with C12 at ambient temperature

[I] PhCH2SH + C H 2 0 HC1 + PhCH2SCH2C1 HOAc

[4] PhCH2SCHCICH, + C12/H20 PhCH2SOrCI

C12IH2O --------+ PhCH2C1 + ClCH2S02Cl HOAc

(38%) (54%)

We have, subsequently, subjected bis(thiobenzy1)methane to exhaustive aqueous chlorinolysis which furnished the results shown in eq. [2]

The results shown in eq. [2] are in complete accord with our previous results on methyl sulfides as well as with our ex- pectation that dithioacetals will dissociate to furnish thionium ions and sulfenyl chlorides following chlorosulfonium cation formation (vide Scheme 2). We note that these results (i) support our past proposal (1) that unsubstituted thionium ions react with chloride ions in preference to water molecules, (ii) offer further support to Wilson's proposal (I 1) that thionium ions are intermediates in the chlorinolyses of simple sulfides, and (iii) offer additional support to our contention (2) that thionium ions are unable to isomerize to the more stable regioisomeric thionium ions under normal conditions (2, 6).

We then chlorinated 1 ,I-bis(thiobenzy1)ethane 5 (eq. [3]) and a-chloroethyl benzyl sulfide 6 (eq. [4]).

These results suggest the intermediacy of the thionium ion derived from 6 via unimolecular dissociation followed by hydrolysis prior to reaction with Clz. Since we were concerned that significant hydrolysis may have occurred before the introduction of CI,, and because we wished to learn more about the course of the conversion of 6 + 4, we have undertaken a series of partial chlorinolyses of 6 in which chlorine was introduced before the sulfide. The results of this series of partial chlorinolyses are presented in Table 1, and show that a-alkyl-a- chlorosulfides dissociate to form chlorine-free thionium ions (in aqueous acetic acid) faster than they react with limited amounts of Clz to furnish chlorosulfonium cations, clearly ruling out a-chloro-chlorosulfonium cations as principal intermediates in the chlorinolysis of dialkyl sulfides.

While it remains unclear whether a-chlorosulfides intervene in these reactions, it is clear that hydrolysis of the chlorine-free thionium ion is the principal pathway by which the reactions proceed.

To complete our study of these systems we have chlorinated the dithioketal 7 as depicted in eq. [5].

C12/H20 [5] (PhCH2S)2C(CH,)r -2 PhCH2SOzCl

HOAc

The change in behaviour of unalkylated thionium ions vs. alkylated thionium ions vis-B-vis hydrolysis could have been anticipated on the grounds that alkyl groups are more electron releasing than hydrogen atoms. In order to see whether selected thionium ions have gas phase stabilities which parallel their ease of formation in solution, or whether solvent effects must be invoked to rationalize the apparently greater facility of alkylated thionium ion formation, we have undertaken a modest MNDO study of the appropriate species A,'

'We intend the present MNDO study to supplement the one we have recently published (6).

BAUM ET AL

TABLE 2. MNDO heats of formation and substituent effects on energetics of thionium ion formation

Sulfides AHc (kcal/mol) Thionium ions A H f (kcal/mol) A A H f AAHr

TABLE 3. MNDO results on selected thionium ions

AHr a Bond a Electron Thionium ion (kcal/mol) order CS population S

MNDO calculations - method and results Computations on a selected series of thionium ions and their

corresponding sulfides were done using the MNDO (Modified Neglect of Differential Overlap) semi-empirical method described previously (6). Geometries were fully optimized except that the phenyl rings were constrained to be planar, with equal C-C bond lengths, C-H bond lengths, and 120" HCC and CCC bond angles.

The calculated heats of formation for the compounds studied are listed in Table 2. The AHf's are consistent with our earlier results (6) except that the sulfide geometry is slightly more stable (0.2 kcal) with the Ph-C bond trans, instead of cis, to The 5 - c ~ ~ bond in benzyl methyl sulfide. This added stability for the phenyl-substituted sulfides increases with alkyl substitution. The important point is that the stability of the phenyl-substituted thionium ion increases with alkylation of the sp2 carbon, as indicated by the decreasing AHf's.

The CS .rr bond orders and .rr electron populations at S are tabulated for the thionium ions in Table 3. As the thionium ion stability increases, the .rr bond order decreases and the .rr electron population at S increases. These trends agree with our previous calculations (6) and indicate that the electron- releasing alkyl substituent is acting through the thionium ion .rr system to stabilize the system.

Mechanistic and pathway conclusions The calculated AH, values for the appropriate sulfides and

the corresponding thionium ions (see Table 2) permit one to obtain AAH, values for the reaction shown in eq. [6] relative to the reaction in eq. [7].

[6] ZYCHSCHZPH + ZYC = k H 2 P h + fi

Calculated AAH, results, reflecting the impact on thionium ion I energetics of progressively incoprorating methyl groups on sp2

carbon, are presented in Table 2. These results indicate that solvent effects, while potentially important, do not need to be invoked to make calculated gas phase stabilities compatible with our solution phase results. The higher presumed inherent reactivity of A (R' = R' = H) over the other thionium ions, previously advanced to rationalize the preference for the un-

substituted thionium ion for chloride ions over water molecules, is compatible with our MNDO results. Scheme 3 presents our conclusions about the pathway followed by dialkyl sulfides upon exhaustive aqueous chlorinolysis.

The original version of the sulfohaloform reaction (1) was based on an extrapolation of detailed study of aqueous chlorinolyses of a-polychloromethyl sulfides and sulfoxides. The first intermediate for this reaction is shown in eq. [8] (X = Cl).

Since that time, similar behaviour has been observed for sulfides bearing an a-sulfonyl group (4) or two a-fluorine atoms (12). Parallel behaviour has also been suggested for sulfides bearing an a-carboxyl group (13). The intermediacy of the corresponding sulfoxide in the aqueous chlorinolysis of a sulfide is clearly the result of hydrolysis of the first formed chlorosulfonium cation (depicted in Scheme 1). The hydrolysis is evidently faster than the competing elimination reaction which would otherwise produce a thionium ion.

We conclude that aqueous chlorinolysis of sulfides is not as simple as originally proposed. The following facts have emerged: ( i ) highly electronegative substituents attached to an a-carbon in the sulfide substrate accelerate hydrolysis of the first formed chlorosulfonium chloride salt leading to formation of a sulfoxide, (ii) sulfides without strongly electronegative a-groups form thionium ions which react preferentially with the chloride counter ions leading to formation of an a-chlorosulfide, and (iii) the presence of inductive stabilizers (i.e., alkyl groups) on sp2 carbon results in the intermediacy of thionium ions which hydrolyze. Scheme 4 presents this more complex array of pathways as The Revised Sulfohaloform Reaction.

Experimental Aqueous chlorinolysis of I

Crude benzyl chloromethyl sulfide (6.935 g) (14) was dissolved in glacial acetic acid (25 mL) and water (3 mL). Clz (ca. 200 mL/min) was bubbled into the reaction mixture for 2 h. The reaction mixture was maintained between 20 and 30°C with an ice/water bath as necessary. Methylene chloride (100 mL) and water (50 mL) were added and the layers separated. The organic layer was washed with 2.5% w/v sodium hydroxide (two 50-mL aliquots). The organic layer was dried (MgS04) and concentrated, affording a crude mixture which contained phenylmethanesulfonyl chloride (0.728 g) , chloromethanesulfonyl chloride (3.182 g), benzyl chloride (1.930 g), and benzyl acetate (0.970 g). The bulk of the phenylmethanesulfonyl chloride crystallized from the crude and was filtered off. It was shown to be identical to authentic material by ir, nmr, and tlc.

The filtered concentrated crude was chromatographed on silica gel (400 g) employing carbon tetrachloride elution (100-mL fractions). Fractions 12- 18 were concentrated and combined, affording benzyl chloride which was identical to authentic material by nmr, ir, and tlc.

CAN. J. CHEM. VOL. 62. 1984

-

C121H20 I R C H ~ ~ C H ~ R ' HOAc RCH2SCH2R' + :CI: ( R , R = alkyl)

Y

Fractions 37-40 were concentrated and combined, affording clean chloromethanesulfony1 chloride which was identical with authentic material by ir and nmr.

Aqueous chlorinolvsis of 3 Bis(thiobenzy1)methane 3 (5.007 g) was suspended in glacial acetic

acid (25 mL) and water (5 mL). The reaction mixture was chlorinated and worked up as described above. Phcnylmethanesulfonyl chloride (1.394 g) crystallized from the crude and was shown to be identical with authentic material by mp, ir, and nmr.

The filtered concentrated crude mixture was rectified at reduced pressure, affording a mixture (bp 120- 130°C/ 100 Torr) ( 1 Tom = 133.3 Pa) which contained chloromethanesulfonyl chloride (1.532 g), benzyl acetate (0.289 g), and benzyl chloride (1.729 g). The identity of the components was established by the addition of authentic compounds which, in each case, increased the intensity of the expected signals in the nmr spectrum of the mixture.

Aqueous chlorinol~ysis of 5 I , I-Bis(thiobenzy1)ethane 5 (5.002 g) was added to glacial acetic

acid (25 mL) and water (5 mL). The reaction mixture was chlorinated and worked up as described above. The residue (5.050 g) was shown to be identical to authentic phenylmethanesulfonyl chloride by nmr, tlc, and mp.

Preparation of PhCHZSCH=CH2 Sodium metal (0.8025 g) was dissolved in refluxing 2-propanol (30

mL). A solution of PhCHzSCHzCHzCl (6.038 g) (15) in 2-propanol (30 mL) was added and the reaction mixture refluxed for 1 h. Water (60 mL) was added and the resultant mixture washed with chloroform (four 60-mL portions). The combined organic layers were dried and concentrated. The residue was rectified at reduced pressure, affording clean benzyl vinyl sulfide (3.166 g, bp 52-56"C/0.4 Torr) which had ir (CHCI,): 1585 cm-'; nrnr (CDCI3) 6: 3.86 (2H, s), 5.20 ( I H, d , J,,, 2 15 HZ), 5.26 ( IH , d , J I 1 HZ), 6.36 (1H. 4, J A x = 15 HZ, JBX = 11 Hz); Cmr (CDCI,) 6: 35.71, 1 1 1.01, 126.73, 128.10, 128.34, 131.66, 136.75; ms tn/e: 150 (M:, 28.6%) and 91 (100%).

(50 mL). HCI (ca. 200 mL/min) was bubbled into the reaction mixture for 1 h. The solvent was evaporated and the residue rectified at reduced pressure, affording PhCH2SCHCICH3 (3.847 g. bp 92-93OC/ 0.9 Torr) which had nrnr (CDCI,) 6: 1.86 (3H. d). 3.90 (2H, s), 4.96 ( IH , q) , and 7.33 (5H, s); msmle: 188 (5.8%), 186(M:, 17.6%). 151 (25%), and 91 (!00%).

Exhaustive aqueous chlorinolysis of 6 The chlorosulfide (5.0160 g) was added to glacial acetic acid (25

mL) and water (5 mL). The reaction mixture was chlorinated and worked up as described above. An nrnr of the crude showed no observable a-chloroethanesulfonyl chloride present. 'The residue was crystallized from carbon tetrachloride, affording phenylmethanesulfonyl chloride (3.747 g) which was identical with authentic material by ir, nmr, mp, and mixture mp.

Controlled aqueorrs chlorinolysis of 6 A series of chlorinolyses of 6 were conducted. The results are

presented in Table 1. Details below are provided for the second run. Water (10 mL) was saturated with Clz at ambient temperature.

Glacial acetic acid (25 mL) was saturated with C12 at room temperature. The chlorosulfide 6 (1.0084 g) was added to the CI2/H20, HOAc/CI2, and glacial acetic acid (25 mL) and the reaction mixture stirred at ambient temperature for 0.5 h. Water (50 mL) was added and the resultant mixture bashed with chloroform (three 75-mL aliquots). The combined organic layers were washed with 2.5% w/v sodium hydroxide (four 50-mL aliquots). The organic layer was dried and concentrated, affording a residue which contained benzyl acetate (0.164 g), phenylmethanesulfonyl chloride (0.3 1 16 g), benzyl chloride (0.1205 g), dibenzyl disulfide (0.066 g). and 1.1-bis(thio- benzy1)ethane (0.129 g).

The crude residue was chromatographed on silica gel (100 g) employing carbon tetrachloride elution (100-mL fractions). Fraction 4 contained benzyl chloride and dibenzyl disulfide. The presence of benzyl chloride was confirmed by the addition of authentic material and observing the change in intensity of the appropriate signals in the nrnr spectrum of the mixture. Fraction 5 afforded clean dibenzyl

Preparation of 6 disulfide which was identical to authentic material by ir, nmr, and tlc. Benzyl vinyl sulfide (5.006 g) was dissolved in carbon tetrachloride Fractions 6- 10 were combined and concentrated, affording

BAUM ET AL.

SCHEME 4. The reviscd sulfohaloforrn reaction

I, I-bis(thiobenzyl)cthane which was identical with authentic material by ir, nmr, and tlc. Fractions 13- 18 were combined and concentrated, affording phenylrnethanesulfonyl chloride which was identical to authentic material by ir, nmr, and tlc. Fraction 31 was combined with a final elution with diethyl ether (400 rnL). Upon concentration of this eluent, benzyl acetate was obtaincd which was identical with authentic material by ir, nmr, and tlc.

Aqueous chlorinolysis of 7 2,2-Bis(thiobenzy1)propane (1.0190 g) was added to glacial acetic

acid (50 rnL) and water (10 mL). The reaction mixture was chlorinated and worked up as described above, furnishing clean crystalline phenylrnethancsulfonyl chloride (1.1948 g).

Acknowledgments T h e authors are indebted to Dr. J . H. K i m w h o ran the mass

spectra and Dr. D. L. Hooper who ran the I3C nmr spectrum. W e are grateful to Mount Allison University for financial support in the early stages o f the work and t o the Florida Institute of Technology for financial support in the latter stages o f the work and for the use o f F . I .T. computing facilities.

1. J . S. GROSSERT and R. F. LANGLER. Can. J . Chern. 55, 407 I ( 1977). I 2. T . P. AHERN, D. G. KAY, and R. F. LANGLER. Can. J . Chern. 56,

2422 (1978).

3. J. R. HANCOCK, W. R. HARDSTAFF, P . A. JOHNS, R . F. LAN- GLER, and W. S. MANTLE. Can. J . Chern. 61, 1472 (1983).

4. D. G. KAY, R. F. LANGLER, and J . E. TRENHOLM. Can J. Chern. 57, 2185 (1979).

5. T. DURST, K. C. T I N , and M. J . V. MARCIL. Can J. Chem. 51, 1704 ( 1973).

6. J. L. GINSBURG and R . F. LANGLER. Can J . Chern. 61, 589 (1983).

7. 9. M. TROST, M. VAULTIER, and M. L. SANTIAGO. J . Am. Chern. Soc. 102, 7029 ( 1 980).

8. R . F. LANGLER. Can J . Chern. 54, 498 (1976). 9 . H. BOHME and H. GRAN. Justus Licbigs Ann. Chern. 577, 68

(1952). 10. R. KUHN and F. A. NEUGEBAUER. Ber. Dtsch. Chern. Ges. 94,

2629 (1961). l I . G . E. WILSON, JR. and M. G. HUANG. J. Org. Chern. 35, 3002

(1970). 12. G. G. 1. Moore. J. Org. Chem. 44, 1708 (1979). 13. R. F. LANGLER, Z. A. MARINI, and E. S . SPALDING. Can. J.

Chem. 57, 3193 (1979). 14. L. A. PAQUEITE, L. S . WI~TENBROOK, and K. SCHREIBER. J.

Org. Chern. 33, 1080 (1968). 15. H. 0 . FONG, W. R. HARDSTAFF, D. G. KAY, R . F. LANGLER, R.

H. MORSE, and D. N. SANDOVAL. Can. J . Chem. 57, 1206 (1979).

The sanlfohaloform reaction. The stepwise conversion of ...

Documents

Transcript of The sanlfohaloform reaction. The stepwise conversion of ...