The imidazole-catalysed isomerisation of benzylpenicillin

Abstract

The isomerisation of benzylpenicillin to benzylpenicillenic acid is catalysed by imidazole, N-methylimidazole, and 2-methylimidazole. For each catalyst there is a different rate equation. The dominant reaction path is general acid assisted reaction of benzylpenicillin with imidazole. A mechanism is proposed in which, after reaction with the imidazole at the carbonyl group of the β-lactam ring, there is protonation of the β-lactam nitrogen and ring-opening. The mechanism proposed parallels that suggested by Morris and Page for the aminolysis of penicillins.