Competitive endo- and exo-cyclic C–N fission in the hydrolysis of N-aroyl β-lactams

Abstract

The balance between endo- and exo-cyclic C–N fission in the hydrolysis of N-aroyl β-lactams shows that the difference in reactivity between strained β-lactams and their acyclic analogues is minimal. Attack of hydroxide ion occurs preferentially at the exocyclic acyl centre rather than that of the β-lactam during the hydrolysis of N-p-nitrobenzoyl β-lactam. In general, both endo- and exo-cyclic C–N bond fission occurs in the alkaline hydrolysis of N-aroyl β-lactams, the ratio of which varies with the aryl substituent. Hence, the Brønsted β-values differ for the two processes: –0.55 for the ring-opening reaction and –1.54 for the exocyclic C–N bond fission reaction. For the pH-independent and acid-catalysed hydrolysis of N-benzoyl β-lactam, less than 3% of products are derived from exocyclic C–N bond fission. Key words: β-lactams, hydrolysis, linear free energy relationships, strain.