Alcohol-catalysed hydrolysis of benzylpenicillin

The hydrolysis of benzylpenicillin is catalysed by alkoxide ions and other oxygen bases. Catalysis occurs by a nucleophilic pathway and the intermediate ester can be detected in some cases. The Brønsted nuc for alkoxide ions is 0.97, and is compatible with rate-limiting ring opening of the -lactam. A solvent isotope effect of 3.2 for the trifluoroethanol-catalysed reaction suggests protonation by water occurs to the departing -lactam nitrogen. Penicillin is not a particularly effective acylating agent of alcohols