Intra- and inter-molecular catalysis in the aminolysis of benzylpenicillin

Abstract

The rate law for the aminolysis of benzylpenicillin in water is reported. The Brønsted β-values for the uncatalysed, the amine-catalysed, and hydroxide-ion catalysed reactions are 1.0, 1.09, and 0.96 respectively. This indicates that in the transition states for all three pathways the amine nucleophile contains a unit positive charge which is consistent with the formation of a tetrahedral intermediate. Intramolecular general base catalysis occurs with the reaction of ethylenediamine and, despite the importance of general base catalysis in the aminolysis reaction, the effective concentration of the catalysing base is only ca. 1M, which is attributed to the ‘loose’ transition state involved in intermolecular catalysis. Intramolecular general acid catalysis occurs with the reaction of ethylenediamine monocation. This suggests that nucleophilic attack takes place from the least hindered α-side.