Reactivity and Mechanism in the Hydrolysis of β-Sultams

Abstract

β-Sultams show extraordinary rate enhancements of 10 9 - and 10 7 -fold, respectively, compared with the acid- and base-catalyzed hydrolysis of corresponding acyclic sulfonamides. They are about 10 3 -fold more reactive than analogous β-lactams. The alkaline hydrolysis of some β-sultams shows a rate term that is second-order in hydroxide ion concentration, which is indicative of a stepwise mechanism involving a trigonal bipyramidal intermediate (TBPI). The Brønsted β lg value for the alkaline hydrolysis of N -aryl-β-sultams is −0.58 and the kinetic solvent isotope effect / is 0.60, compatible with rate-limiting formation of the TBPI. Conversely, / for N -alkyl-β-sultams is 1.55, indicative of rate-limiting breakdown of the TBPI. The acid-catalyzed hydrolysis of β-sultams is strongly retarded by electron-withdrawing groups α to the sulfonyl group, and it is suggested that the mechanism may involve unimolecular ring opening to generate a sulfonylium ion. The Brønsted β lg value for the acid-catalyzed hydrolysis of N -benzyl-β-sultams is 0.32. The general-acid-catalyzed hydrolysis of N -benzyl-β-sultam by carboxylic acids shows a Brønsted α value of 0.67 and is attributed to a specific acid−nucleophilic mechanism with the formation of a mixed-anhydride intermediate.