The Mechanisms of Hydrolysis of the y-Lactam lsatin and its Derivatives

The pH dependences of the rates of hydrolysis of isatin, its N-carboxymethyl derivative and its 5-nitro substituted analogues exhibit a complex behaviour, showing a first- and second-order dependence upon hydroxide ion concentration, as well as a pH-independent pathway. The pH dependence is interpreted in terms of the formation of tetrahedral intermediates in different protonic states which may break down to products via hydroxide ion, hydronium ion and water catalysed pathways. These γ-lactams are as reactive, or more reactive, than benzylpenicillin.