Chloromethyl Methyl Sulfide


[2375-51-5]  · C2H5ClS  · Chloromethyl Methyl Sulfide  · (MW 96.58)

(protection of carboxylic acids and alcohols;1 introduces a methyl2 or methylene3 unit on carbon or nitrogen;4 preparation of vinyl sulfides;5 corresponding Grignard reagent reacts with various electrophiles;6 oxidative additions with various metals7)

Alternate Name: methylthiomethyl chloride; MTMCl.

Physical Data: bp 38 °C/55 mmHg, 52 °C/100 mmHg, 107 °C/750 mmHg; d20 1.1773 g cm-3.

Solubility: sol acetonitrile, ether, dichloromethane.

Form Supplied in: colorless liquid; commercially available.

Handling, Storage, and Precautions: hydrolyzes easily; flammable; exhibits obnoxious odor. Use in a fume hood.

Protective Group.

Carboxylic acids react with chloromethyl methyl sulfide (MTMCl) to give MTM esters (eq 1).1,8-11 This protective group is stable for 1 h in contact with an aqueous solution of pH 0-15.9 It is also stable to sodium borohydride and Zn-MeOH.8 Primary and secondary alcohols12,13 and phenols14 react with MTMCl to yield the corresponding MTM ethers (eq 2). The MTM ether function is stable to basic, nucleophilic, and mild acidic conditions (aq AcOH).12,14 Various mild conditions can be used for selective deprotection.1

Electrophilic Reagent.

Silyl enol ethers react with MTMCl in the presence of Iodotrimethylsilane15 or Zinc Bromide3 to give methylthiomethylated products (eq 3).3 The methylthio group can be removed reductively to accomplish an overall methylation. Oxidative removal of the methylthio group provides a way for a-methylenation of carbonyl compounds (eq 3).3 Other carbon nucleophiles that react with MTMCl include aromatic compounds,2 stabilized carbanions,16,17 and organotin acetylides.18 Similarly, introduction of the MTM group on nitrogen with MTMCl provides a way for eventual methylation19 or methylenation.4,20,21 Phosphonates (eq 4),5,22 phosphine oxides,23 or phosphorus ylides24 derived from MTMCl have been used in the preparation of vinyl sulfides, which lead to the corresponding ketones after hydrolysis.5

Reaction with Metals.

The Grignard reagent prepared from MTMCl reacts with various electrophiles (eq 5).6 Oxidative additions of transition metals (Pt, Pd, Ni, Fe) with MTMCl give organometallic compounds containing the methylthiomethyl ligand.7,25-29 These compounds have been prepared because of interest in their structures and reactions.

Related Reagents.

Chloromethyl Phenyl Sulfide.

1. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; 2nd ed.; Wiley: New York, 1991.
2. Hendrickson, J. B.; DeCapite, P. M. JOC 1985, 50, 2112.
3. Paterson, I. T 1988, 44, 4207.
4. Khatri, N. A.; Schmitthenner, H. F.; Shringarpure, J.; Weinreb, S. M. JACS 1981, 103, 6387.
5. Corey, E. J.; Shulman, J. I. JOC 1970, 35, 777.
6. Ogura, K.; Fujita, M.; Takahashi, K.; Iida, H. CL 1982, 1697.
7. McPherson, H. D.; Wardell, J. L. JOM 1983, 254, 261.
8. Ho, T.-L.; Wong, C. M. CC 1973, 224.
9. Wade, L. G., Jr.; Gerdes, J. M.; Wirth, R. P. TL 1978, 731.
10. Ono, N.; Yamada, T.; Saito, T.; Tanaka, K.; Kaji, A. BCJ 1978, 51, 2401.
11. Shono, T.; Ishige, O.; Uyama, H.; Kashimura, S. JOC 1986, 51, 546.
12. Corey, E. J.; Bock, M. G. TL 1975, 3269.
13. Suzuki, K.; Inanaga, J.; Yamaguchi, M. CL 1979, 1277.
14. Holton, R. A.; Davis, R. G. TL 1977, 533.
15. Hosomi, A.; Sakata, Y.; Sakurai, H. CL 1983, 405.
16. Mock, W. L.; Tsay, J.-T. SC 1988, 18, 769.
17. Schöllkopf, U.; Busse, U.; Kilger, R.; Lehr, P. S 1984, 271.
18. Zhai, D.; Zhai, W.; Williams, R. M. JACS 1988, 110, 2501.
19. Bernardi, L.; de Castiglione, R.; Scarponi, U. CC 1975, 320.
20. Kim, J. K.; Souma, Y.; Beutow, N.; Ibbeson, C.; Caserio, M. C. JOC 1989, 54, 1714.
21. Fiocca, L.; Fiorenza, M.; Reginato, G.; Ricci, A. JOM 1988, 341, C23.
22. Green, M. JCS 1963, 1324.
23. Grayson, J. I.; Warren, S. JCS(P1) 1977, 2263.
24. Cameron, A. G.; Hewson, A. T. JCS(P1) 1983, 2979.
25. Yoshida, G.; Kurosawa, H.; Okawara, R. JOM 1977, 131, 309.
26. McPherson, H. M.; Wardell, J. L. ICA 1983, 75, 37.
27. Davidson, J. G.; Barefield, E. K.; van Derveer, D. G. OM 1985, 4, 1178.
28. Mattson, M. N.; Bays, J. P.; Zakutansky, J.; Stolarski, V.; Helquist, P. JOC 1989, 54, 2467.
29. Karsch, H. H. CB 1977, 110, 2699.

Yeun-Min Tsai

National Taiwan University, Taipei, Republic of China

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