Methanesulfenyl Chloride1

MeSCl

[5813-48-9]  · CH3ClS  · Methanesulfenyl Chloride  · (MW 82.56)

(reacts as a pseudohalogen;1 reacts with carbanions and enolates to add the thiomethyl group a to the carbonyl;2,3 adds across the double bonds of alkenes and allenes;4,5 adds across triple bond of alkynes6,7)

Physical Data: bp 27-28 °C/53-60 mmHg.

Solubility: sol ether, THF, dichloromethane, chloroform, carbon tetrachloride, dimethoxyethane.

Preparative Methods: by treatment of Dimethyl Disulfide at -15 °C with Sulfuryl Chloride, or by treatment of Methanethiol with Chlorine gas in CCl4 at -15 °C.1 The latter procedure may be considered a variation of the former since it involves the intermediate formation of the disulfide. The reagent is not commercially available.

Purification: can be used crude from the above preparations. If purification is necessary it must be distilled at low temperature, under vacuum, due to its instability.

Handling, Storage, and Precautions: undergoes decomposition within 1-2 d even when kept in a refrigerator; lasts less than 1 month when stored at -78 °C.

Reaction with Nucleophilic Heteroatoms.

Methanesulfenyl chloride reacts with most N nucleophiles in a manner which can be considered as a direct substitution. Reaction with amines has recently found a use in the preparation of 7-methoxycephalosporins (eq 1).8

Methanesulfenyl chloride reacts similarly with thiols and other sulfur nucleophiles to give disulfides.9 The reaction with alcohols gives complex mixtures of products and is not generally useful.10 Alkoxides, however, react with methanesulfenyl chloride to give methanesulfenate esters when 1 equiv or less of methanesulfenyl chloride is employed (eq 2); methylsulfinate esters are formed when a 0.5 M excess of methanesulfenyl chloride is used (eq 3).10

Reaction with Carbanions.

Methanesulfenyl chloride has also been used to thiomethylate carbanions, forming thiomethyl ethers (eq 4).2

Reaction with Alkenes, Allenes, and Alkynes.

Methanesulfenyl chloride adds to alkenes to give anti adducts with high stereoselectivity and proceeds through a thiiranium ion intermediate.1,4 For additions to unsymmetrically substituted alkenes the ratio of regioisomers is governed by the steric requirements of the alkene substituents, and to an extent the nature of the solvent used, but gives predominantly anti-Markovnikov addition with alkyl substituted alkenes (Table 1).4,6 In general, methanesulfenyl chloride tends to give a higher ratio of anti-Markovnikov adducts than do arenesulfenyl chlorides.11

Reaction with allenes is similar with addition generally occuring at the least substituted double bond.5

The reaction of methanesulfenyl chloride with alkynes is similar to that with alkenes.1 The addition is stereospecifically anti and goes through a thiirenium ion intermediate to give predominantly anti-Markovnikov products.6,7

The high regio- and stereoselectivity characteristic of the addition of methanesulfenyl chloride, and sulfenyl halides in general, to alkenes, allenes, alkynes, and other p-nucleophiles make this reaction very useful. This is especially so when the substrate contains an internal nucleophilic center capable of competing with chloride ion for attack of the thiiranium or thiirenium ion intermediate, such as in sulfenolactonization (eq 5),12 or when there is additional functionality present which may participate (eq 6).13 In eq 6 the methanesulfenyl chloride initially adds to the allene to give a thiiranium ion which is then attacked by the isolated double bond.

Reaction with Enols and Enolates.

Methanesulfenyl chloride reacts with enols and enolates to give a-sulfenylated carbonyls (eq 7).3,14,15


1. (a) Capozzi, G.; Modena, G.; Pasquato, L. In The Chemistry of Sulphenic Acids and their Derivatives; Patai, S., Ed.; Wiley: New York, 1990; p 403. (b) Kuehle, E. The Chemistry of Sulphenic Acids; Theime: Stuttgart, 1973.
2. Bravo, P.; Gaviraghi, G. JHC 1977, 14, 37.
3. Williams, R. M.; Rastetter, W. H. JOC 1980, 45, 2625.
4. Mueller, W. H. AG(E) 1969, 8, 482.
5. Mueller, W. H.; Butler, P. E. JOC 1968, 33, 1533.
6. Mueller, W. H.; Butler, P. E. JACS 1968, 2075.
7. Calo, V.; Scorrano, G. G 1968, 98, 545.
8. Tsuji, T.; Itani, H.; Ishitobi, H. TL 1987, 28, 2745.
9. Harpp, D. N.; Friedlander, B. T.; Larsen, C.; Steliou, K.; Stockton, A. JOC 1978, 43, 3481.
10. Moore, T. L.; O'Connor, D. E. JOC 1966, 31, 3587.
11. Schmid, G. H.; Csizmadia, V. M. CJC 1972, 50, 2465.
12. Huckstep, M. R.; Taylor, R. J. K. TL 1986, 27, 5919.
13. Angelov, C. M.; Kirilov, M.; Vachkov, K. V.; Spassov, S. L. TL 1980, 21, 3507.
14. Kissman, H. M.; Schaub, R. E.; Weiss, M. J. JMC 1967, 10, 252.
15. Mikolajczyk, M.; Kielbasinski, P.; Grzejszczak, S. S 1983, 332.

Helen M. Organ

Merck Research Laboratories, Rahway, NJ, USA



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