Reactivity and mechanism in the hydrolysis of β-sultams

beta-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 beta-lactams. The alkaline hydrolysis of some beta-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 Bronsted beta(Ig) value for the alkaline hydrolysis of N-aryl-beta-sultams is -0.58 and the kinetic solvent isotope effect k(OH)(H2O)/k(OD)(D2O) is 0.60,compatible with rate-limiting formation of the TBPI. Conversely, k(OH)(H2O)/k(OD)(D2O) for N-alhyl-beta-sultams is 1.55, indicative of rate-limiting breakdown of the TBPI. The acid-catalyzed hydrolysis of beta-sultams is strongly retarded by electron-withdrawing groups ct to the sulfonyl group, and it is suggested that the mechanism may involve unimolecular ring opening to generate a sulfonylium ion. The Bronsted beta(Ig) value for the acid-catalyzed hydrolysis of N-benzyl-beta-sultams is 0.32. The general-acid-catalyzed hydrolysis of N-benzyl-beta-sultam by carboxylic acids shows a Bronsted a value of 0.67 and is attributed to a specific acid-nucleophilic mechanism with the formation of a mixed-anhydride intermediate.