[CONTRIBUTION FBOY T
m NOYJCS
CHEMICAL LABOBATORY, UNIVERSITY OF ILLINOIS]
LEVINSTEIN MUSTARD GAS. I. 2-HALOALKYLSULFENYL HALIDES' REYWOLD C. FUSON, CHARLES C. PRICE, ROBERT A. BAUMAN, ORVILLE H . BULLITT, JR., WILLIAM R. HATCHARD, AND EVERETT W. MAYNERT Received March 16, 19.46
Since the development, during World War I, of the Levinstein process for making mustard gas many attempts have been made to follow the course of the reaction and to determine the nature of the contaminants. The research reported in this series of papers was directed to this same end. It was a cooperative effort, valuable assistance being received from many sources, notably the Chemical Warfare Service. One of the most interesting theories in this connection, put forth by Conant, Hartshorn, and Richardson (l),postulated 2-chloroethylsulfenyl chloride (I) as an intermediate in the formation of mustard gas (11) by the condensation of ethylene with sulfur chlorides. With sulfur dichloride, for example, the reactions would be as follows:
+ SClp + ClCHsCHpSCl I ClCH2CH2SCl + C H I ~ * H (ClCH,CH&S ~ CHn--CH*
I1 Similar equations can be written for the Levinstein process, which involves the condensation of ethylene with sulfur monochloride a t 35". However, these investigators, as well as Mann and Pope (2), failed to obtain the sulfenyl chloride in pure form. In the present work it has been found possible to produce 2chloroethylsulfenyl chloride by the chlorinolysis of bis(2-chloroethyl) disulfide (111). (CICH&Hs)&
+ Cln
--+
2 ClCR&HsSCl
I11 The sulfenyl chloride is an orange-colored liquid with an odor resembling that of the sulfur halides. It decomposes, slowly at room temperature and very rapidly a t 110", with the evolution of hydrogen chloride and the formation of a black tar. The sulfenyl chloride can be purified by distillation; it boils undecomposed a t 47-47.5" (15 mm.). 2-Chloroethylsulfenyl chloride is the first sulfenyl halide with alpha hydrogen atoms to be prepared by the chlorinolysis of a disulfide. In fact, the only other sulfenyl halides with alpha hydrogen atoms are those formed by the action of 1 This paper is based on work done for the Officeof Scientific Research and Development under Contracts Nos. OEMsr-300 and OEMsr-48 with the Board of Trustees of the University of Illinois. 469
470
R. c. FUSOX, c. c. PRICE, et al.
sufur dichloride on N ,N’-di-n-propylmalonamide and the AT, N’-dir aphthylmalcnamides (3). The reacticns of 2-chloroethylsulfc1~ylchloride are similar t o thuse cf sulfcnyl halides in general. It was reccnverted t o the origin21 bis(2-chlorcethyl) disulfide with aqueous potassium icdide. Treatrrent cf the sulfenyl chlcride M ith water also produced the disulfide, together v ith unidentified malcdorous material which mas probably the thiolsulfcnic ester (4). Oxidatic n n ith dilute nitric acid yielded 2-chloroethanesulfcnic acid, n hich was isolated as the axxmi nium salt. 2-Chlcroethylsulfeny1chloride reacted readily with sulfur t o yield a mixture of products including sulfur monochloride, bis(2-chloroethyl) disulfide and bis(2-chloroethyl) trisulfide. 2 ClCHzCHzSCl
+ XS
+ (C1CHzCHz)zSX
+ SzClz
A similar result has been reported by Klascn (5) for the reacticn between sulfur and trichloromethylsulfenyl chloride. Such a reacticn was postulated by Conant, Hartshorn, and Richardscn (1) as a pcssible source of the polysulfides present in Levinstein mustard gas; the sulfur was assumed to arise from dismutaticn of the sulfur mcnochloride. The most interesting reacticns cf 2-chlorcethylsulfenyl chloride are those with olefins, particularly that 1% ith ethylene. When ethylene was bubbled through the pure sulfenyl chloride no reacticn took place. If the sulfenyl chloride was dissolved in carbon tetrachloride, however, reacticn m ith ethylene was extrerrely rapid with the evoluticn of heat and the formaticn of bis(2-chloroethyl) sulfide. This result substantiates the hypothesis of Conant, Hartshorn and Richards: n that 2-chlorcethylsulfer.yl chloride is an intermediate in the preparation of mustard gas from ethylene and sulfur chlorides. The failure to obtain a reaction in the absence of a solvent is probably due to the low solubility of ethylene in the sulfenyl chloride. A similar observaticn has been made in the reacticn of ethylene with sulfur mcn7chloride; the reaction is extremely slow unless a solvent or “seed charge’’ is employed (6). The cnly examples of the additicn of sulfenyl chlorides to olefins which are reported in the literature involve ethylene (7). In the present work it has been found that this type of reacticn is general for olefins. Cyclohexene, for example, combines with 2-chloroethylsulfenyl chloride to form 2-chlorocyclohexyl 2-chloroethyl sulfide.
In a similar manner, it has been found possible to condense 2-chloroethylsulfenyl chloride with acetylene to produce 2-chloroethyl 2-chlorovinyl sulfide. A compariscn cf properties shows this sulfide to be identical with that obtained by Lawson and Dawson (8) by the action of clilorine on bis(2-chloroethyl)sulfide.
LEVINSTEIN MUSTARD GAS.
47 1
I
Thus t’he unequivocal synthesis reported here serves to confirm the conclusion of thefe authors that their product was 2-chloroet,hyl 2-chlorovinyl sulfide. 2-Chloroethylsulfeny1chloride reacts normally with active methylene compound:;; for example, its ccndensation 1%ith acetone produced acetonyl 2-chloroethyl sulfide. ClCHzCHzSCl
+ CH3COCHZ
--+
ClCHZCHzSCH2COCH3
+ HCI
Likewise, it condensed readily with piperazine to form a disulfenamide, N ,hr’bis(2-chloroethy1thio)piperazine. 2-Chloroethylsulfenyl bromide was prepared by a method simiiar to that used for making 2-chloroethylsulfenyl chloride. Treatment of bis(2-chloroethyl) disulfide with bromine produced a red liquid, which fumed in. moist air and possessed a characteristic sulfur halide odor. It was too unstable to be distilled. However, it was found possible t o condense the crude reaction product with cyclohexene to produce 2-bromocyclohexyl 2-chloroethyl sulfide.
+ Br1:
(C1CH2CH2)2S2
3
2 ClCH2CH2SBr
The mixed sulfide was characterized by the preparation of its p-toluenesulfilimine derivative . EXPERIMENTAL
8-Chloroethylsulfenyl chloride. To a well-agitated solution of 453 g. (2.37 moles) of bis(2-chloroethyl) disulfide, prepared according to the method of Bennett (9), in dry carbon tetrachloride was added 169 g. (2.88 moles) of chlorine at such a rate that the t :mperature did not rise above 10’. The solvent. was evaporated a t reduced pressure and the product was distilled; b.p. 47-47.5’ (15 mm.); n’,”1.5290; yield 355 g., or 5770. I n other runs yields up to 79% have been obtained. The sulfenyl chloride was a n orange liquid with avery unpleasant odor. It was moderately stable when stored in a brown bottle and kept in the refrigerator. It was necessary t o distil it immediately before using. Anal. Calc’d for C2H4Cl&: C, 18.33; H, 3.07. Found: C, 18.30; 13, 3.03. The residue from the original distillation of the 2-chloroethylsulfeny1 chloride weighed 173 g. and contained bis(2-chloroethyl) disulfide and a new compound which had the composition of a monochloro derivative of the disulfide. The two compounds were obtained from the residue by fractional distillation. The new compound was a yellow liquid (n*k81.5768) which on standing darkened and developed a disagreeable odor. Anal. Calc’d for C4H,C1&: C, 21.29; H, 3.13; C1, 47.15. Found: C, 21.94; H, 3.17; C1,47.02. Reactions of 2-chloroethylsulfenyl chloride. a. With potassium iodide. A sample of the sulfenyl chloride was dissolved in aqueous acetone and treated with potassium iodide. The iodine formed was removed with sodium sulfite, and the acetone was evaporated. The insoluble oil was taken up in chloroform and dried over sodium sulfate. Removal of the solvent left a colorless oil, n! 1.5608, with a n odor resembling that of bis(2-chloroethyl) disulfide (for the pure disulfide n; 1.5656). b. With water. Twenty grams of the sulfenyl chloride and 300 ml. of water were placed
472
R.
c.
FUSON,
c. c. PRICE,
et
al.
in a glass-stoppered flask and agitated mechanically. The orange color of the chloride soon disappeared, leaving the hydrolysis product as a colorless oil. It was dried with sodium sulfate and fractionally distilled under diminished pressure. It was possible to isolate bis(2-chloroethyl) disulfide; b.p. 83-88' (2 mm.); n g 1.5670; m.p. 1'. A small amount of higher-boiling liquid could not be characterized. C . With sulfur. An equimolar mixture of 2-chloroethylsulfenyl chloride and sulfur was heated a t 60-65' for three hours. The product, a clear orange liquid, was distilled under diminished pressure. A volatile fraction containing sulfur monochloride was obtained followed by a higher-boiling fraction of bis(2-chloroethyl) disulfide (9) and trisulfide (IO). The latter were separated by fractionation in vacuo (0.2 mm.), and identified by comparison of their physical properties with authentic specimens. d. Oxidation with nitric acid. T o an aqueous solution of 4.8 g. of the sulfenyl chloride was added dropwise with stirring 30 ml. of nitric acid (d. 1.42). The mixture was heated on a steam-bath until clear, and evaporated t o dryness. An excess of ammonium hydroxide was added; the resulting solution, upon evaporation, yielded crystals which melted at 191-193' after recrystallization from ethanol. Ammonium 2-chloroethanesulfonate is reported (11) to melt a t 194". The total yield was 4.2 g. (79%). e. Wzfh ethylene. Ethylene gas was conducted into a solution of 10 g. of the sulfenyl chloride in 90 ml. of carbon tetrachloride. Heat was liberated and the reddish-orange color of the solution disappeared in a short time, leaving the reaction mixture water-white. The solvent was evaporated on a steam-bath and the product distilled under reduced presRure. It consisted of bis(2-chloroethyl) sulfide; b.p. 54-55' (1 mm.); n: 1.5281 (12). The yield was 7ooj0. f. With cyclohexene. T o 9.0 g. of the sulfenyl chloride was added slowly 7.0 g. of cyclohexene dissolved in 25 ml. of carbon tetrachloride. Distillation of the colorless reaction mixture yielded 10 g. (66%) of 2-chlorocyclohexyl 2-chloroethyl sulfide; b.p. 84-86' (0.2 mm.). The p-toluenesulfilimine was made by mixing a solution of 1 g. of the sulfide in 5 ml. of acetone with 20 ml. of a 10% aqueous solution of Chloramine-T. The mixture was warmed slightly, shaken for a few minutes, and allowed to stand one hour. The crystalline product was removed and recrystallized from ethanol; m.p. 145.5446" in a preheated bath. Anal. Calc'd for C16HllCI2NO&3):C, 47.12; H, 5.54; N, 3.66. Found: C, 47.04; H, 5.47; N, 3.69. g. Wilh acetylene. 2-Chloroethyl2-chlorovinyl sulfide was prepared by the condensation of the sulfenyl chloride with acetylene. Fifteen hundred milliliters of ethyl acetate was cooled in a n ice-salt bath and acetylene (dried by passing through concentrated sulfuric acid) was bubbled in, with stirring, for one and one-half hours. Then, with continued addition of acetylene, 185 g. of the sulfenyl chloride was added dropwise over a period of two hours. One hour later the addition of acetylene was discontinued and the solvent was removed by distillation with a water-pump. The residual oil was distilled through a 6-in column packed with Berl Saddles. The yield of colorless 2-chloroethyl 2-chlorovinyl sulfide was 125 g., or 56%; b.p. 46" (0.75 mm.), 30" (0.15 mm.); n: 1.5480; m.p. -24". Anal. Calc'd for CdHsCl*S: C, 30.60; H, 3.85; C1,45.16; S, 20.39. Found: C, 30.81; H, 3.99; C1,M.O; S, 21.2. The p-toluenesulfilimine of this product was prepared in the usual way. It was recryatallized successively from absolute ethanol and carbon tetrachloride ; m.p. 105405.5'. Anal. Calc'd for C1lH&lzNO&: C, 40.51; H, 4.02; N, 4.29. Found: C, 40.58; H, 4.18; N, 4.26. The sulfone, prepared in the usual way (13), crystallized from low-boiling petroleum ether in white platelets; m.p. 37.538". Anal. Calc'd for CdH&l*O&S: C, 25.41; H, 3.20. Found: C, 25.37; H, 3.18. h. W i t h acetone. Thirty-five grams of the freshly-distilled sulfenyl chloride was added to 50 g. of dry acetone. An exothermic reaction occurred, accompanied by rapid decoloriza-
LEVINSTEIN MUSTARD GAS. I
473
tion of the mixture and the evolution of hydrogen chloride. When the reaction was complete, waler was added and a n oily layer separated. It was dried over anhydrous sodium sulfate and distilled through a column packed with Berl Saddles; b.p. 76-85’ (0.75 mm.). The acetonyl2-chloroethyl sulfide was characterized by preparation of the semicarbazone, which Kas recrystallized from methanol; m.p. 145-146’. Anal. Calc’d for C&Il&lNSOS: C, 34.36; H, 5.77. Found: C, 34.31; H, 5.80. i. With piperazine. This reaction was carried out according to the directions of Rheinboldt and Mott (14) for the corresponding derivative with l-butylsulfenyl chloride. The N,N’-bis(2-~hloroethylthio)piperazinecrystallized from absolute ethanol as white needles; m.p. 117-118”. Anal. Calc’d for CoHlbCl*hT2S2: C, 34.90; H, 5.86. Found: C, 35.17; H, 5.55. 8-Bronzocyclohexyl 8-chloroethyl sulfide. Eighty grams of bromine was added over a period of one hour to a solution of 95 g. of bis(2-chloroethyl) disulfide in 150 ml. of carbon tetrachloride. After the mixture had been stirred overnight, the solvent and unchanged bromine were removed by distillation in vacuo a t room temperature. The 2-chloroethylsulfenyl bromide remained as a red liquid which had the odor characteristic of sulfur halides. It fumed when exposed to moist air and decomposed into the starting materials when attempts were made to distil i t at a pressure of 3 mm. I n another experiment cyclohexene was added to a carbon tetrachloride solution of the sulfenyl bromide. The red color of the solution gradually faded and the mixture assumed the light yellow color of the product, 2-bromocyclohexyl2-chloroethyl sulfide. The crude sulfide, which was obtained in a 75% yield, decomposed slightly during distillation a t 0.35 mm. The p-toZuenesul$Zimine, made in the usual way, was recrystallized from ethanol; map. 145-146”. Anal. Calc’d for ClsH21BrClN02S2:C, 42.21; H, 4.96. Found: C, 42.61; H, 4.77. SUMMARY
2-Chloroethylsuifenyl chloride has been made by the action of chlorine on bis(2-chloroethyl) disulfide. It has been cocdensed with ethylene to produce bis(Pchloroethy1) sulfide; this result further substantiates the belief that it is an intermediate in the formation of mustard gas from ethyleEe and sulfur chlorides. It has been colzdensed with cyclohexex?e to produce 2-chlorocyclohexyl 2chloroethyl sulfide, with acetylene to yield 2-chloroethyl 2-chlorovinyl sulfide, with acetoce to form acetonyl 2-chloroethyl sulfide, and with piperazine to give N ,N’-bis(2-~hloroethyIthio)piperazine. 2-Chloroethylsulfenyl bromide has been obtair.ed in crude form by the action of brorriii.e on bis(2-chloroethyl) disulfide. The bromide was found to combine nrith cyclohexene t o yield 2-bromocyclohexyl 2-chloroethyl sulfide. URBANA, ILL. REFERENCES (1) CONANT, HARTSHORN, AND RICHARDSON, J. Am. Chem. SOC.,42,585 (1920).
(2) h‘fANN A N D POPE, J. Chem. SOC., 121, 594 (1922). (3) NAIK AND JADHAR, Quarterly J. I n d . Chem. SOC., 3, 260 (1926). (4) CONNOB in Gilman, “Organic Chemistry,” Ed. 2, John Wiley, New York, 1943, p. 921.
474 (5) (6) (7) (8) (9)
(10) (11) (12) (13) (14)
R.
c.
FUSON,
c. c.
PRICE,
et aZ.
KLASON, Ber., 20, 2376 (1887). GIBSONAND POPE,J. Chem. Soc., 117, 271 (1920). LECHER, Ber., 68, 409 (1925). LAWSON AND DAWSON, J . Am. Chem. SOC.,49, 3119 (1927). J. Chem. Soc., 119, 418 (1921); see also BENNETT, FUSON,PRICE,BURNESS,FOSTER, HATCHARD, AND LIPSCOMB, J . Org. Chem., Paper IV of this series. MANN,POPE,AND VERNON, J . Chem. Soc., 119, 634 (1921). Am. Chem. J., 19, 749 (1897). KOHLER, JACKSON, Chem. Revs., 16, 425 (1934). Ber., 43, 289 (1910). HINSBEHO, AND MOTT,Ber., 72, 668 (1939). RHEINBOLDT
