Methoxycarbonylmethanesulfonyl Chloride

[56146-83-9]  · C3H5ClO4S  · Methoxycarbonylmethanesulfonyl Chloride  · (MW 172.60)

(synthesis of sultam analogs of b-lactams;3 synthesis of biologically active sulfonamides4-6)

Physical Data: bp 98 °C/8 mm Hg; d 1.505 g cm-3; fp >110 °C.

Solubility: sol C6H6, CH2Cl2, Et2O.

Form Supplied in: colorless liquid.

Analysis of Reagent Purity: reagent purity may be determined by standard analytical techniques.

Preparative Methods: from chlorosulfonylacetyl chloride by reaction with 1 equiv of methanol;1 may also be prepared by chlorination of sodium methoxycarbonylmethanesulfonate with Phosphorus(V) Chloride2 or by direct chlorination of methyl thioglycolate.3

Purification: distillation under reduced pressure.

Handling, Storage, and Precautions: moisture sensitive; causes burns.

Synthesis of b-Sultams.3

Formation of the b-sultam (eq 1) proceeds via addition of methoxycarbonylmethanesulfonyl chloride to a solution of the desired imine (1 equiv) and a tertiary amine base (1.5 equiv) at -78 °C. Best results are obtained using THF as the solvent and Pyridine as the base. Yields are moderate to high. In general, the yields are higher when the R1 substituent is aryl rather than alkyl.

Synthesis of Sulfonamides.4-6

Sulfonamides are formed in moderate to good yields by the reaction of methoxycarbonylmethanesulfonyl chloride with the desired amine in the presence of Triethylamine (eq 2). This reaction is usually carried out using arylamines, but can be extended to peptidic amines.6

1. Vieillefosse, R. BSF 1947, 351.
2. Oliver, J. E.; DeMilo, A. B. S 1975, 321.
3. Szymonifka, M. J.; Heck, J. V. TL 1989, 30, 2869.
4. Baltas, M.; Cazaux, L.; de Blic, A.; Gorrichon, L.; Tisnes, P.; Touati, A. BSF 1988, 79.
5. Musser, J. H.; Kreft, A. F.; Bender, R. W. H.; Kubrak, D. M.; Carlson, R. P.; Chang, J.; Hand, J. M. JMC 1989, 32, 1176.
6. Zecchini, G. P.; Paradisi, M. P.; Torrini, I.; Lucente, G.; Gavuzzo, E.; Mazza, F.; Pochetti, G. TL 1991, 32, 6779.

Susan Champion

University of Bristol, UK

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