Structure–reactivity relationships and the mechanism of general base catalysis in the hydrolysis of a hydroxy-amide. Concerted breakdown of a tetrahedral intermediate

Abstract

Kinetic general base catalysis is observed in the lactonisation of N-substituted endo-6-hydroxybicyclo[2.2.1]-heptane-endo-2-carboxamides. The reaction mechanism is thought to involve the kinetically equivalent general-acid-catalysed breakdown of the tetrahedral intermediate, T^–. The Brønsted β values for the catalysed lactonisation of the N-propyl- and N-trifluoroethyl-amides are 0.70 and 0.50, respectively which are equivalent to α values of 0.30 and 0.50, respectively. These values are indicative of a concerted reaction in which proton transfer occurs synchronously with carbon–nitrogen bond fission. The dependence of the rate of reaction of N-substituted amides upon the acidity of the catalyst shows that β_1g decreases with increasing acidity of the catalyst. The behaviour of the observed structure–reactivity coefficients is discussed with the aid of energy diagrams and it is concluded that proton transfer makes a significant contribution to the reaction co-ordinate. The structure–reactivity coefficients also indicate a degree of charge imbalance in the transition state.