Evidence for a trigonal bipyramidal intermediate during nucleophilic substitution at a sulfonyl centre and for a sulfonylium cation in the acid catalysed reaction

β-SultamsMechanism of Reactions and Use as Inhibitors of Serine Proteases

“…Electron-withdrawing substituents R to the sulfonyl group have a very large retarding effect upon the rate of acid-catalyzed hydrolysis and generate a very negative Hammett F I value. 15 These observations are compatible with a unimolecular process to form the sulfonylium ion 6. There are no well-established cases for these intermediates during substitution at sulfonyl centers, 4 but their intermediacy in β-sultam hydrolysis is compatible with the similar acylium ion mechanism suggested for the acid-catalyzed hydrolysis of β-lactams.…”

“…The combination of this with the relief of ring strain permits the possible involvement of a unimolecular A1 process to form an electron-deficient sulfonylium ion intermediate 6 , which could then be trapped by water to form the β-aminosulfonic acid product. Electron-withdrawing substituents α to the sulfonyl group have a very large retarding effect upon the rate of acid-catalyzed hydrolysis and generate a very negative Hammett ρ I value . These observations are compatible with a unimolecular process to form the sulfonylium ion 6 .…”

“…4 However, rates of the alkaline hydrolysis of some β-sultams are second-order in hydroxide ion, which is strong evidence for the formation of a trigonal bipyramidal intermediate (TBPI) with a hypervalent sulfur. 15 Initial but reversible attack of hydroxide ion on the β-sultam generates a monoanionic TBPI -, which requires deprotonation by a second hydroxide ion before the intermediate can collapse to products (Scheme 3). 8 There is a difference in the timing of the proton transfer and possibly rate-limiting steps for the alkaline hydrolysis of N-aryl and N-alkyl β-sultams.…”