Synthesis of α-fluoro- and α,α-difluoro-benzenemethanesulfonamides: new inhibitors of carbonic anhydrase

Abstract

Direct fluorination of arenemethanesulfonamide anions under mild conditions and in high yield has been accomplished using N-fluorobisbenzenesulfonimide, NFSi, on carbanions of N-tert-butyl- and N-bis-(4-methoxyphenyl-methyl)-benzenemethanesulfonamides giving novel α-fluoro- and α,α-difluoro-benzenemethanesulfonamides respectively: IC₅₀ and pK_a data show that α-halogenation enhances sulfonamide acidity incrementally and correlates well with increased carbonic anhydrase inhibition, while lipophilicity is also enhanced.