Substituent effects in the acid solvolysis of para-substituted hippuric acids in acetic acid at low water concentrations. Neighbouring group participation by the carboxy-group

Abstract

The rates of acid solvolysis of the para-substituted hippuric acids in acetic acid decrease with an increasing acid concentration for Cl, H, Me, and OMe indicating that the rate-controlling step is the ring closure reaction by the non-protonated amide to form an intermediate azlactone or its solvate. The acid–base equilibrium constants derived from the kinetic data vary in accordance with their substituent effects. Although the velocity constants show an irregular sequence, the products of the equilibrium and velocity constants vary as required by the substituent effects. This is in agreement with the reaction rate being dependent upon the zwitterion concentration through which the ring closure proceeds. The NO2 group behaves differently from the other groups and gives only increasing rates with increasing acid concentrations and this behaviour is consistent with that of other strongly electronegative groups such as the trifluoroacetyl and the positive terminal amino-group of a dipeptide. These groups favour ring closure so that the acid catalysed ring fission of the azlactone solvate becomes the slow reaction.