Ethylene Sulfide1

[420-12-2]  · C2H4S  · Ethylene Sulfide  · (MW 60.13)

(mercaptoethylation reagent for primary and secondary amines2)

Alternate Name: thiirane.

Physical Data: bp 55-56 °C; d 1.010 g cm-3; nD20 1.4935.

Solubility: insol H2O; sol most common organic solvents.

Form Supplied in: colorless liquid; commercially available, stabilized with 0.5% BuSH.

Analysis of Reagent Purity: by IR,3a 1H NMR,3b and GLC.4

Preparative Methods: readily obtained from ethylene carbonate and Potassium Thiocyanate.5

Handling, Storage, and Precautions: highly toxic,6 flammable liquid; must be stored in a freezer to prevent gradual polymerization, which is promoted by mineral and organic acids, bases, aqueous ammonia, strong amines, and heavy metal salts. Stabilizers against polymerization: H2S, alkyl and benzyl thiols, alkyl sulfides, and thioacetamide. Use in a fume hood.

Mercaptoethylation of Amines.

Ethylene sulfide is widely used for mercaptoethylation of primary and secondary amine groups in various organic compounds to obtain aminothiols themselves or to convert them into sulfur heterocycles. Aqueous ammonia causes only a rapid polymerization of ethylene sulfide and no cysteamine formation. The action of anhydrous ammonia has not been investigated. Efforts to obtain monomeric ethylene sulfide addition products to Hydrazine and Hydroxylamine failed.

Mercaptoethylation of amines by ethylene sulfide proceeds with opening of the episulfide ring by an SN2 mechanism, the slow step being nucleophilic attack of the amine on the episulfide carbon atom followed by a rapid proton exchange between N and S atoms.7 Strongly basic amines react more rapidly,8 but high basicity promotes polymerization of ethylene sulfide as well.9 The latter reaction may be suppressed by using nonpolar solvents (benzene, ether, THF, dioxane) and an excess of the amine, which also prevents the formation of bis(mercaptoethyl) derivatives in the case of primary amines and further alkylation of product at sulfur (giving thioethers).10 Heating favors the mercaptoethylation reaction and diminishes the polymerization.11

A substantial improvement of the earlier synthetic procedures is the gradual addition of the ethylene sulfide to a refluxing amine solution in benzene, which diminishes the polymerization to less than 1%.2 This procedure with warm, but not refluxing, solution gives good yields even when stoichiometric amounts of reagents are used (eq 1).12 Primary aliphatic amines may be mercaptoethylated near room temperature in aqueous media containing the amine-silver complex, which finally is decomposed by H2S (eq 2).13

Weakly basic aryl amines,8 esters of aminobenzoic acids,14 and a-amino acids15 require more drastic conditions (100-105 °C, sealed tube, alcoholic solutions or absence of solvent) for mercaptoethylation.

The preparation of bis(mercaptoethyl)amines by means of ethylene sulfide has been little investigated,11,16 and reaction conditions have not been optimized. However, satisfactory yields of HN(CH2CH2SH)2 (83%) and N(CH2CH2SH)3 (72%) were obtained by slowly treating cysteamine with an excess of ethylene sulfide at rt in toluene followed by refluxing (24 and 36 h, respectively).17

Other Applications.

Other useful applications of ethylene sulfide for the synthesis of organosulfur compounds in excellent yields (>90%): PhCH2SCH2CH2Br,18 PhSCH2CH2SH,19 R2AsSCH2CH2SCN,20 1,4-dithiane,21 1,3-dithiolane-2-thione,22 and a thiazolidine derivative of the C20 diterpenoid alkaloid lindheimerine by cyclocondensation of its N=C bond with ethylene sulfide.23

Related Reagents.


1. (a) Reynolds, D. D.; Fields, D. L. Chemistry of Heterocyclic Compounds: Heterocyclic Compounds with Three- and Four-Membered Rings; Interscience: New York, 1964; Vol. 19, Part 1, pp 576-623. (b) Sander, M. CRV 1966, 66, 297. (c) Fokin, A. V.; Kolomiets, A. F. Usp. Khim. 1975, 44, 306. (d) Fokin, A. V.; Kolomiets, A. F. Usp. Khim. 1976, 45, 71. (e) Fokin, A. V.; Kolomiets, A. F. Chemistry of Thiiranes; Nauka: Moscow, 1978 (CA 1979, 91, 140 705n). (f) Zoller, U. Chemistry of Heterocyclic Compounds: Small Ring Heterocycles: Aziridines, Azirines, Thiiranes, Thiirenes; Wiley: New York, 1983; Vol. 42, Part 1, pp 333-630.
2. Wineman, R. J.; Gollis, M. N.; James J. C.; Pomponi, A. M. JOC 1962, 27, 4222.
3. (a) The Aldrich Library of FT-IR Spectra; Aldrich Chemical: Milwaukee, 1989; Vol. 3, p 354C. (b) The Aldrich Library of NMR Spectra, 2nd ed.; Aldrich Chemical: Milwaukee, 1983; Vol. 1, p 231C.
4. Golovnya, R. V.; Garbuzov, V. G.; Aerov, A. F. IZV (Engl. Transl.) 1979, 28, 1630.
5. Fieser, L. F.; Fieser, M. FF 1967, 1, 378.
6. Brown, J. R.; Mastromatteo, E. Am. Ind. Hyg. Assoc. J. 1964, 25, 560.
7. Oddon, A.; Wylde J. BSF(2) 1967, 1603.
8. Rachinskii, F. I.; Slavachevskaia, N. M.; Ioffe, D. V. JGU 1958, 28, 3027.
9. Braz, G. I. JGU 1951, 21, 757.
10. Snyder, H. R.; Stewart, J. M.; Ziegler, J. B. JACS 1947, 69, 2672.
11. Marabella, C. P.; Enemark, J. H.; Miller, K. F.; Bruce, A. E.; Pariyadath, N.; Corbin, J. L.; Stiefel E. I. IC 1983, 22, 3456.
12. Karlin, K. D.; Lippard S. J. JACS 1976, 98, 6951.
13. Luhowy, R.; Meneghini, F. JOC 1973, 38, 2405.
14. Yuryev, Yu. K.; Dyatlovitskaya, S. V. JGU 1957, 27, 1855.
15. Bulavin, L. G. JOU 1971, 7, 2168.
16. (a) Bulavin, L. G. JOU 1971, 7, 2703. (b) Corbin, J. L.; Miller, K. F.; Pariyadath, N.; Wherland, S.; Bruce A. E.; Stiefel, E. I. ICA 1984, 90, 41.
17. Rima, G.; Satge, J.; Fatome, M.; Laval, J. D.; Sentenac-Roumanou H.; Lion, C.; Lazraq, M. Eur. J. Med. Chem. 1991, 26, 291.
18. Trujillo, D. A.; McMahon, W. A., Jr.; Lyle, R. E. JOC 1987, 52, 2932.
19. Fokin, A. V.; Kolomiets, A. F.; Rudnitskaya, L. S.; Shevchenko, V. I. IZV(Engl. Transl.) 1975, 24, 582.
20. Fokin, A. V.; Kolomiets, A. F.; Levskaya, G. S. IZV (Engl. Transl.) 1975, 24, 334.
21. Yuryev, Yu. K.; German, L. S. JGU 1955, 25, 2421.
22. Razuvaev, G. A.; Etlis, V. S.; Grobov, L. N. JOU 1963, 33, 1335.
23. Pelletier, S. W.; Nowacki, J.; Mody, N. V. SC 1979, 9, 201.

Gunars Zelčans

Institute of Organic Synthesis, Riga, Latvia

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.