Methanesulfonic Anhydride


[7143-01-3]  · C2H6O5S2  · Methanesulfonic Anhydride  · (MW 174.22)

(preparation of sulfonates1-3)

Physical Data: mp 69-70 °C; bp 125 °C/4 mmHg.

Solubility: sol organic solvents.

Form Supplied in: off-white powder; widely available.

Purification: can be recrystallized from diethyl ether.

Handling, Storage, and Precautions: corrosive; moisture sensitive. Store in a cool, dry place.

Sulfonate Formation.

The preparation of an alkyl methanesulfonate from an alcohol can be achieved by treatment of an alcohol with methanesulfonic anhydride in the presence of Pyridine or 2,4,6-Collidine (eq 1).1 The use of methanesulfonic anhydride rather than Methanesulfonyl Chloride eliminates the formation of small amounts of alkyl chlorides which occurs when methanesulfonyl chloride is used. Methanesulfonic anhydride, however, does not work very well for the formation of mesylates of unsaturated alcohols. Glycosyl mesylates (eq 2)2,3 and 11-O-methylsulfonylerythromycins4 have been synthesized using methanesulfonic anhydride.

Glycosyl mesylates can be converted to glycosides by treatment with alcohols, and have also been used as intermediates in the synthesis of oxyglycals. Preparation of methyl ethers by solvolysis of mesylates in methanol has been reported.5 Treatment of glycidols with methanesulfonic anhydride yields the epoxy mesylate which can then be treated with Tellurium to produce the allyl alcohol (eq 3).6

Sulfonamide Formation.

Treatment of amines with methanesulfonic anhydride in acetonitrile yields the methanesulfonamide (eq 4).7 Sulfonamides are versatile protecting groups for the amino group, displaying good stability to both acidic and basic conditions. The sulfonamide group can be cleaved by Lithium Aluminum Hydride or dissolving metal reductions. Methanesulfonamides are also present in some biologically active molecules.

Sulfone Formation.

Friedel-Crafts methylsulfonation of benzene or substituted benzenes can be achieved via treatment with methanesulfonic anhydride in the presence of a Lewis acid catalyst (eqs 5 and 6).8,9 Unlike methanesulfonyl chloride, which sulfonates only activated benzenes, treatment of deactivated benzenes with methanesulfonic anhydride produces the desired sulfones in good yields.8,10 Diaryl sulfones can be formed using methanesulfonic anhydride and Sulfuric Acid (eq 7).11

Oxidation of Alcohols.

Primary and secondary alcohols can be oxidized to aldehydes and ketones in good yields via treatment with methanesulfonic anhydride and Dimethyl Sulfoxide in HMPA (eqs 8 and 9). Dichloromethane can be substituted as the solvent, but the use of HMPA leads to cleaner products. Methanesulfonic anhydride works especially well for the conversion of primary alcohols to aldehydes.12 Benzylic aldehydes can also be formed using this method.

Related Reagents.

Acetic Anhydride; Benzoyl Chloride; Dimethyl Sulfoxide-Methanesulfonic Anhydride; Methanesulfonyl Chloride; p-Toluenesulfonyl Chloride; Trifluoroacetic Anhydride.

1. Mangold, H. K. Chem. Phys. Lipids 1973, 10, 354.
2. Leroux, J.; Perlin, A. S. Carbohydr. Res. 1978, 67, 163.
3. Jones, G. S.; Scott, W. J. JACS 1992, 114, 1491.
4. Tadanier, J.; Martin, J. R.; Egan, R. S.; Goldstein, A. W.; Stanaszek, R. S.; Hirner, E.; Fischer, F. JOC 1974, 39, 2495.
5. Danishefsky, S.; Morris, J.; Mullen, G.; Gammill, R. JACS 1980, 102, 2838.
6. Discordia, R. P.; Dittmer, D. C. JOC 1990, 55, 1414.
7. Lis, R.; Morgan, T. K., Jr.; Marisca, A. J.; Gomez, R. P.; Lind, J. M.; Davey, D. D.; Phillips, G. B.; Sullivan, M. E. JMC 1990, 33, 2883.
8. (a) Fieser, L. F.; Fieser, M. FF 1967, 1, 667. (b) Fieser, M. FF 1990, 15, 201.
9. Olah, G. A.; Kobayashi, S.; Nishimura, J. JACS 1973, 95, 564.
10. Ono, M.; Nakamura, Y.; Sato, S.; Itoh, I. CL 1988, 395.
11. (a) Tyobeka, T. E.; Weigel, H. S. Afr. J. Chem. 1990, 43, 71. (b) Tyobeka, T. E.; Hancock, R. A.; Weigel, H. CC 1980, 114.
12. Albright, J. D. JOC 1974, 39, 1977.

Valerie Vaillancourt & Michele M. Cudahy

The Upjohn Co., Kalamazoo, MI, USA

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