[ C O N T R I B U T I O N FRObl T H E NOYES C H E M I C A L
LABORATORY, UNIVERSITY
OF
ILLIXOIS 1
2-CHLOROETHYL 2-HYDROXYETHYL SULFIDE' REYNOLD C. FUSON
AND
J. BENJAMIN ZIEGLER, JR.
Received March 15, 1946
2-Chloroethyl 2-hydroxyethyl sulfide (I) is of interest because it is the half hydrolysis product of mustard gas (1). Of the various methods which might be suitable for its synthesis (2) that of Saleberg and Lazier (3) seemed most promising. This method, which has been described also by Morrison, Rueggeberg, and Dawson (4),involves photochemical addition of mercaptans to olefins. I n the present work it has been found possible to condense monothioglycol with vinyl chloride in satisfactory yields. HOCHzCHzSH
+ CH:,=CHCl-+
HOCH2CH2SCH2CH2Cl
I
The same reaction was carried out, apparently while this work was in progress, by Rueggeherg and Cook ( 5 ) under somewhat different conditions. The 2-chloroethyl 2-hydroxyethyl sulfide can be converted to mustard gas in high yield by treatment with concentrated hydrochloric acid. It was characterized further by the preparation of the p-toluenesulfilimine, the morpholyldithiocarbamate, and the a-naphthylurethan. 2-Chloroethyl 2-hydroxyethyl sulfide was found to boil almost undecomposed at 100" (0.6 mm.). At room temperatures it decomposed almost completely in four days. The criterion of degree of decomposition was the change in the refractive index. The refractive index, when taken immediately after distillation, \vas ':n 1.5188. When the liquid was allowed to stand the index rose gradually to 1.5600. At temperatures near 0" the compound was comparatively Cl-CH,CH:,Cl +/ 2 HOCH2CH2SCHZCH2Cl -+ HOCHzCH2S
\
C1- CHzCH2 +/
/
S
CHZCH,
+
Cl\+
HOCHzCHzS
SCHzCHiOH
/
SCH2CHzOH CH:, CH:,
\
S
-+
+ 2 HOCH2CHzCl
1 This parer is based on work done for the Office of Scientific Research and Development under Contracts Nos. OEMsr-300 and OEMsr-48 with the Board of Trustees of the University of Illinois.
510
2-CHLOROETHYL 2-HYDROXYETHYL SULFIDE
511
stable; a sample which had been kept at this temperature for one week was distilled with 75% recovery of pure material. When the compound was stored in solid carbon dioxide it appeared to remain unchanged. The decomposition products of this compound have never been investigated thoroughly. It was noted, however, that large amounts of p-dithiane collected in the condenser during the distillation of the 2-chloroethyl 2-hydroxyethyl sulfide. The following mechanism for the formation of p-dithiane seems probable on the basis of the work of Bell, Bennett, and Hock (6). Treatment of 2-chloroethyl 2-hydroxyethyl sulfide with ethanolic sodium hydroxide yielded, instead of the desired 2-hydroxyethyl vinyl sulfide, a mixture of 1 , 4-tmhioxnneand 2-ethoxyethyl 2-hydroxyethyl sulfide. EXPERIMENTAL
Synthesis of 2-chloroethyl I-hydroxyethyl sulfide. The procedure of Salzberg and Lazier (3) w;ss followed. A mixture of 39 g. of redistilled monothioglycol, and 0.8 g. of benzoyl peroxide was placed in a EM-ml. quartz flask and cooled t o about -30" in a dry-ice bath. From 75 t o 95 g. of liquid vinyl chloride was added to the reaction mixture, which was connected immediately t o a thimble-type reflux condenser filled with powdered dry ice. A calcium chloride tube was connected t o the outlet tube of the condenser. The reaction mixture was irradiated for four hours with an ultraviolet lamp, an additional 0.4 g. of the peroxide added, and irradiation continued for another four hours. The mixture was allowed to stand overnight a t room temperature; during this time the vinyl chloride gradually volatilized. Residual low-boiling material was removed under diminished pressure and the crude 2-chloroethyl 2-hydroxyethyl sulfide was distilled i n vacuo; b.p. 100' (0.6 mm.) , yield 40 g. (57)%; n t 1.5260. Redistillation produced 31 g. of the pure compound; n! 1.5188. Anal. Calc'd for CJ~&lOS: C, 34.16; H, 6.45; C1, 25.22; S, 22.81. Found: C, 34.14; H, 6.46; C1, 28.39; S, 21.92. Fourteen grams of the chloro hydroxy sulfide was heated under reflux for one hour with 70 ml. of concentrated hydrochloric acid. The yield of mustard gas was 11.6 g.; b.p. 75-80" (0.9-1.0 mm.); m.p. 14.5'; n; 1.5262 (7). With Chloramine-T the compound yielded the m.p. 143.5' (8). known bis(2-chloroethyl)-p-toluenesulfilimine; p-!l'oluenesuljilimine. The p-toluenesulfilimine of 2-chloroethyl 2-hydroxyethyl sulfide, made by the general method of Mann and Pope (8), was found t o exist in dimorphs. The low-melting form crystallized from ethanol in colorless leaflets melting at 122.5-123'. An,rcl. Calc'd for CI1HIBC1NO3S2: C, 42.64; H, 5.21; N, 4.52. Found: C, 43.00; H, 5.03; N, 4.42. The product obtained in another experiment melted a t 137-138". Anal. Found: C, 43.03; H, 5.21; N, 4.72. Mixtures of the high-melting form with the p-toluenesulfilimine of mustard gas (m.p. 144") and with p-toluenesulfonamide(m.p.135") melted, respectively, at 122-123' and 103.5105.5'. A mixture of the dimorphic sulfilimines melted at 137-137.5". Seeding the lowmelting with the high-melting form caused the melting point t o change from 122.5-123' t o 137-138'. Morpholyldithiocarbamate. T o a solution of 7.5 g. of potassium morpholyldithiocarbamate (9) in 100 ml. of 45% ethanol was added a solution of 5.0 g. of 2-chloroethyl 2-hydroxyethyl sulfide in 10 ml. of 95% ethanol. The mixture was heated under reflux for one hour and poured into 500 ml. of water. The oil which separated was found to solidify; m.p. 64-65'. The solid was dissolved in the minimum amount of hot 75% ethanol and allowed to cool t o room temperature. The fine, long needles which separated were recrystallized from ethanol; m.p. 128.5-129'. A mixture of this material with an authentic specimen of the morpholyldithiocarbamate of mustard gas (2) showed no lowering of the melting point.
612
R.
C. FUSON AND J.
B. ZIEGLER,
JR.
Concentration of the mother liquor yielded a second crop of crystals weighing 4.9 g. It separated from aqueous ethanol in white, pearly leaflets; m.p. 66-67". Anal. Calc'd for C ~ H I ~ N O I SC, I : 40.42; H, 6.41. Found: C, 40.59; H, 6.20. a-Naphlhylurethan. This derivative was made in the usual way and recrystallized from high-boiling petroleum ether. The pure white needles melted at 96.5-97.5". Anal. Calc'd for CloHIGCINOtS: C, 58.15; H, 5.20; N, 4.52. Found: C, 58.15; H, 5.36; N, 4.38. Dehydrohalogenation. T o a solution of 0.21 mole of sodium hydroxide in 100 ml. of absolute ethanol at 10" was added 0.20 mole of 2-chloroethyl 2-hydroxyethyl sulfide. The mixture was heated under reflux for one hour and allowed to stand at room temperature for two days. The sodium chloride was removed by filtration and the filtrate acidified with dry ice. The solvent was removed under diminished pressure and the residue distilled in vacuo Two fractions were obtained. The first fraction (1-2 9.) distilled a t 45-55" (22 mm.); n: 1.4865. This distillate, upon treatment with aqueous Chloramine-T, yielded a sulfilimine; m.p. 147.5-148.5'. A mixture (m.p. 147.5melting point with an authentic sample of 1,4-thioxane-p-toluenesulfilimine 148.5') was not depressed. The sulfilimine used for comparison was prepared from 1,4thioxane which had been made by distilling a mixture of thiodiglycol and concentrated sulfuric acid, a modification of the method of Fromm and Unger (10). Anal. Calc'd for Cl~H15NO3S2: C, 48.33; H , 5.53; N, 5.13. Found: C, 48.04; H, 5.28; N, 5.05. The second fraction [6.3 g., b.p. 115-125' (22 mm.) ] waa redistilled through a modified Claisen head; b.p. 100' (1.5 mm.); n: 1.4800. This distillate absorbed very little bromine from a carbon tetrachloride solution, but reacted with sodium with the evolution of hydrogen. The boiling point and analysis correspond closely to the values for 2-ethoxyethyl 2-hydroxyethyl sulfide (11). Anal. Calc'd for CsHI,OS: C, 47.97; H. 9.39; S, 21.34. Found: C, 48.67; H , 9.54; S, 21.30. SUMMARY
The synthesis of 2-chloroethyl 2-hydroxyethyl sulfide has been accomplished by the addition of monothioglycol to vinyl chloride. The structure of the product has been confirmed by conversion to mustard gas and by the preparation of the p-tolueneaulfilimine, the morpholyldithiocarbamate, and the anaphthylurethan . URBANA,ILL. REFERENCES
PETERS AND WALKER, Biochem. J., 17, 260 (1923); Ogston, British Research Report. Chemical Warfare Service and O.S.R.D. Reports. AND LAZIER, N.D.R.C. Reports. SALZBERG MORRISON, RUEGGEBERG, AND DAWSON, Chemical Warfare Service Reporta. AND COOK,Chemical Warfare Service Report. RUEGGEBERG A N D HOCK,J. Chem. SOC., 1803 (1927). BELL,BENNETT, JACKSON, Chem. Revs.,16, 425 (1934). (8) MANNA N D POPE, J. Chem. SOC., 121, 1052 (1922). (9) FIJSON AND PARHAM, J. Org. Chem., Paper 111, Levinstein Mustard Gas series. (10) FROMM A N D UNGER,Ber., 66, 2286 (1923). A N D OXFORD, J. Chem. SOC.,234 (1931). (11) DAVIES (1) (2) (3) (4) (5) (6) (7)
