Dimethyl Disulfide

MeSSMe

[624-92-0]  · C2H6S2  · Dimethyl Disulfide  · (MW 94.22)

(electrophilic trap for carbanions to prepare methyl sulfides; undergoes homolytic substitution at sulfur with radicals)

Physical Data: mp -85 °C; bp 110 °C; d 1.063 g cm-3.

Solubility: insol H2O; sol alcohol and ether.

Form Supplied in: liquid, widely available.

Purification: passage through neutral alumina.

Handling, Storage, and Precautions: use in a fume hood.

Electrophilic Carbanion Trap.

Dimethyl disulfide undergoes electrophilic attack by carbanions, with cleavage of the weak S-S bond to yield methyl sulfides. Aryllithiums have been most widely used; generation by ortho-lithiation (eq 1),1 metal-halogen exchange (eq 2),2 and intramolecular benzyne trapping (eq 3)3 has been demonstrated. Aryl Grignard reagents4 can also be used. Vinyllithiums effectively trap dimethyl disulfide, providing vinyl sulfides,5 which can be converted into the corresponding ketones. This procedure can be used to effect a 1,2 keto transposition (eq 4).6 Vinyl sulfides have also been prepared via lithiated diphenylphosphine oxide trapping of dimethyl disulfide followed by alkenation with aldehydes or ketones (eq 5).7

Dithioketene acetals can be prepared by metalation of geminal vinyl diiodides (eq 6);8 allenyl enol ethers can also be sulfenated (eq 7).9 Alkyllithiums are effectively sulfenylated (eq 8).10 Less reactive carbanions are also easily trapped by dimethyl disulfide; allyllithiums react to give allylmethyl sulfides (eq 9),11 and benzyllithiums provide benzyl sulfides.12

Sulfenylation a to carbonyl groups is accomplished via the respective enolates.13 Oxidation and subsequent thermally induced elimination provides a route to a,b-unsaturated carbonyls;14 however, this method has been largely supplanted by the corresponding selenenylation sequence15 in which the selenoxide elimination occurs at or below ambient temperature. The advantages of the sulfur variant are the lower cost and lower toxicity of the reagent. Sulfenylation a to carboxylic acids followed by oxidation by N-Chlorosuccinimide or Sodium Periodate effects oxidative decarboxylation16 via a putative Pummerer-like intermediate (eq 10). Introduction of a methyl sulfide group a to benzylic nitriles is best accomplished with the coaddition of Iodomethane (eq 11).17 Lithiated 1,3-dithianes (see 2-Lithio-1,3-dithiane) react readily to provide orthothioformates.18 Addition of an excess of Silver(I) Trifluoromethanesulfonate results in the um polung formation of dithiin carbocations (eq 12),19 whereas Mercury(II) Chloride alcoholysis provides a route to esters.20

Activated Electrophilic Forms of Dimethyl Disulfide.

Electrophilic attack on dimethyl disulfide by non-anionic carbon nucleophiles is best accomplished by the addition of a Lewis acid or a methylating agent to enhance the electrophilicity of the sulfur trap. Electron-rich aromatics and indoles21 are sulfenylated with dimethyl disulfide in the presence of Lewis acids. A combination of dimethyl disulfide and Sulfuryl Chloride can also be used, probably forming sulfenyl chloride in situ as the actual trapping agent (eq 13).22

A number of preformed electrophilic salt derivatives have been developed; the most popular is Dimethyl(methylthio)sulfonium Tetrafluoroborate (DMTSF),23 although sulfonate counterions24 are sometimes used. These reagents react with alkenes to give intermediate episulfonium ions which can be intercepted by nucleophiles such as azide,25 amines,26 acetate, carboxylate, DMSO, cyano,27 Triphenylphosphine,28 and alkynylaluminates (eq 14).29

Disulfenylation of alkenes using a premixed combination of Trifluoromethanesulfonic Acid and Iodosylbenzene with dimethyl disulfide is also effective.30 Reaction of dithioacetals with DMTSF results in thionium ions which can be trapped with allylstannanes (eq 15),31 vinylsilanes, and silyl enol ethers.32 Orthothioesters can be similarly ionized upon treatment with DMTSF.33

Higher order sulfenating reagents (see Methylbis(methylthio)sulfonium Hexachloroantimonate)34 have been developed to generate episulfonium intermediates from alkenes. In these cases, the byproduct dimethyl disulfide is less nucleophilic than the dimethyl sulfide present with DMTSF reactions (eq 16).

Preparation of Isolable Sulfenylation or Sulfoxylation Reagents.

Dimethyl disulfide is used in the preparation of Methanesulfenyl Chloride,35 methanesulfinyl chloride,36 and methyl methanesulfinate.37

Thiol Radical Source and Radical Trap Undergoing SH2 Reaction.

Photolysis of dimethyl disulfide and other disulfides causes homolytic cleavage of the disulfide bond, resulting in formation of thiol radicals, which can be observed by ESR via nitroxyl spin traps.38 Aryl,39 alkyl,40 and perfluoro41 radicals react with dimethyl disulfide in an SH2 displacement to yield the corresponding sulfides (eq 17). Distonic radical cations behave similarly, whereas conventional radical cations do not abstract the methyl sulfide group.42 Dialkyl and diaryl disulfides add to terminal alkenes by a radical mechanism (eq 18).43 The addition of dimethyl disulfide across the cyclopropyl bond of a [3.1.1]propellane is believed to occur by thiol radical attack followed by methyl sulfide abstraction (eq 19).44

Related Reagents.

Diphenyl Disulfide; 2,2-Dipyridyl Disulfide.


1. (a) Shimazaki, M.; Takahashi, M.; Komatsu, H.; Ohta, A.; Kajii, K.; Kodama, Y. S 1992, 555. (b) Stanetty, P.; Koller, H.; Mihovilovic, M. JOC 1992, 57, 6833. (c) Simig, G.; Schlosser, M. TL 1990, 31, 3125.
2. Lipshutz, B. H.; Hagen, W. TL 1992, 33, 5865.
3. Fisher, L. E.; Caroon, J. M. SC 1989, 19, 233.
4. Bordwell, F. G.; Boutan, P. J. JACS 1957, 79, 717.
5. Seebach, D.; Neumann, H. CB 1974, 107, 847.
6. (a) Nakai, T.; Mimura, T. TL 1979, 531. (b) Kano, S.; Yokomatsu, T.; Ono, T.; Hibino, S.; Shibuya, S. CC 1978, 414.
7. Fujimoto, T.; Hotei, Y.; Takeuchi, H.; Tanaka, S.; Ohta, K.; Yamamoto, I. JOC 1991, 56, 4799.
8. Barluenga, J.; Rodriguez, M. A.; Campos, P. J.; Asensio, G. JACS 1988, 110, 5567.
9. (a) Hoff, S.; Brandsma, L.; Arens, J. F. RTC 1968, 87, 1179. (b) Wildschut, G. A.; Brandsma, L.; Arens, J. F. RTC 1969, 88, 1132.
10. Reich, H. J.; Medina, M. A.; Bowe, M. D. JACS 1992, 114, 11003.
11. (a) Degl'Innocenti, A.; Mordini, A.; Pagliai, L.; Ricci, A. SL 1991, 155. (b) Klusener, P. A. A.; Tip, L.; Brandsma, L. T 1991, 47, 2041.
12. Poindexter, G. S.; Foley, M. A.; Licause, J. F. TL 1989, 30, 3393.
13. (a) Chelucci, G.; Giacomelli, G. JHC 1990, 27, 311. (b) Flores-Parra, A.; Gutiérrez-Avella, D. M.; Guzmán-Vázquez, Y. J.; Ariza-Castolo, A.; Contreras, R. JOC 1992, 57, 6067. (c) Gassman, P. G.; Gilbert, D. P.; Cole, S. M. JOC 1977, 42, 3233. (d) Seebach, D.; Teschner, M. TL 1973, 5113.
14. (a) Trost, B. M.; Salzmann, T. N. JACS 1973, 95, 6840. (b) Trost, B. M.; Salzmann, T. N. JOC 1975, 40, 148. (c) Trost, B. M. PAC 1975, 43, 563.
15. Reich, H. J.; Renga, J. M.; Reich, I. L. JACS 1975, 97, 5434.
16. Trost, B. M.; Tamaru, Y. JACS 1977, 99, 3101.
17. Marchand, E.; Morel, G.; Foucaud, A. S 1978, 360.
18. (a) Ellison, R. A.; Woessner, W. D.; Williams, C. C. JOC 1972, 37, 2757. (b) Stütz, P.; Stadler, P. A. OS 1977, 56, 8.
19. Gamage, S. A.; Smith, R. A. J. T 1990, 46, 2111.
20. Woessner, W. D. CL 1976, 43.
21. (a) Ranken, P. F.; McKinnie, B. G. JOC 1989, 54, 2985. (b) Ranken, P. F.; McKinnie, B. G. S 1984, 117. (c) Mukaiyama, T.; Suzuki, K. CL 1993, 1.
22. Tupper, D. E.; Pullar, I. A.; Clemens, J. A.; Fairhurst, J.; Risius, F. C.; Timms, G. H.; Wedley, S. JMC 1993, 36, 912.
23. (a) Meerwein, H.; Zenner, K.-F.; Gipp, R. LA 1965, 688, 67. (b) Smallcombe, S. H.; Caserio, M. C. JACS 1971, 93, 5826.
24. (a) Helmkamp, G. K.; Cassey, H. N.; Olsen, B. A.; Pettitt, D. J. JOC 1965, 30, 933. (b) Helmkamp, G. K.; Olsen, B. A.; Koskinen, J. R. JOC 1965, 30, 1623. (c) Ravenscroft, M.; Roberts, R. M. G.; Tillett, J. G. JCS(P2) 1982, 1569.
25. Trost, B. M.; Shibata, T. JACS 1982, 104, 3225.
26. Caserio, M. C.; Kim, J. K.; JACS 1982, 104, 3231.
27. Trost, B. M.; Shibata, T.; Martin, S. J. JACS 1982, 104, 3228.
28. Okuma, K.; Koike, T.; Yamamoto, S.; Takeuchi, H.; Yonekura, K.; Ono, M.; Ohta, H. BCJ 1992, 65, 2375.
29. Trost, B. M.; Martin, S. J. JACS 1984, 106, 4263.
30. Kitamura, T.; Matsuyuki, J.; Taniguchi, H. JCS(P1) 1991, 1607.
31. Trost, B. M.; Sato, T. JACS 1985, 107, 719.
32. Trost, B. M.; Murayama, E. JACS 1981, 103, 6529.
33. Caserio, M. C.; Shih, P.; Fisher, C. L. JOC 1991, 56, 5517.
34. (a) Capozzi, G.; Ottana, R.; Romeo, G. H 1986, 24, 583. (b) Weiss, R.; Schlierf, C. S 1976, 323. (c) Capozzi, G.; De Lucchi, O.; Lucchini, V.; Modena, G. S 1976, 677. (d) Capozzi, G.; De Lucchi, O.; Lucchini, V.; Modena, G. TL 1975, 2603.
35. (a) Douglass, I. B.; Farah, B. S. JOC 1959, 24, 973. (b) Douglass, I. B.; Norton, R. V. OSC 1973, 5, 709.
36. Douglass, I. B.; Farah, B. S.; Thomas, E. G. JOC 1961, 26, 1996.
37. (a) Douglass, I. B. JOC 1965, 30, 633. (b) Douglass, I. B. JOC 1974, 39, 563.
38. Mile, B.; Rowlands, C. C.; Sillman, P. D.; Fildes, M. JCS(P2) 1992, 1431.
39. Oae, S.; Sinhama, K.; Kim, Y. H. CL 1979, 939.
40. Brown, H. C.; Midland, M. M. JACS 1971, 93, 3291.
41. (a) Clavel, J. L.; Langlois, B.; Nantermet, R.; Tordeux, M.; Wakselman, C. JCS(P1) 1992, 3371. (b) Haszeldine, R. N.; Rigby, R. B.; Tipping, A. E. JCS(P1) 1972, 159.
42. Stirk, K. M.; Orlowski, J. C.; Leeck, D. T.; Kenttämaa, H. I. JACS 1992, 114, 8604.
43. (a) Kuehne, M. E.; Damon, R. E. JOC 1977, 42, 1825. (b) McPhee, D. J.; Campredon, M.; Lesage, M.; Griller, D. JACS 1989, 111, 7563.
44. Mlinarić-Majerski, K.; Majerski, Z.; Rakvin, B.; Veksli, Z. JOC 1989, 54, 545.

Rebecca Braslau

University of California, Santa Cruz, CA, USA



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