Sulfonamides have been prepared in high yields by the reactions of N-silylamines with sulfonyl chlorides and fluorides. In a competition experiment, the sulfonyl chlorides were found to be far more reactive than sulfonyl fluorides. The chemistry may be used to prepare aliphatic, aromatic, tertiary, secondary, and primary sulfonamides. It may also be done in the absence of solvent and the byproduct trimethylsilyl chloride recovered in good yield. Primary sulfonamides were synthesized from the sulfonyl chloride with aminotriphenyl silane (Ph3SiNH2), a conversion demonstrated with the synthesis of the carbonic anhydrase inhibitor, acetazolamide.
Bibliographical noteFunding Information:
We gratefully acknowledge the support of the NIH-National Institute of General Medical Sciences (GM085736-01A1) and the Northern Illinois University for Great Journeys Fellowship (R.R.N.). This manuscript is dedicated to Rachel A. Klumpp on the occasion of her tenth birthday.
- Sulfonyl transfer