Reactions of carbonyl compounds in basic solutions. Part 14. The alkaline hydrolysis of substituted N-methylformanilides, N-methylacetanilides, 1-phenylazetidin-2-ones, 1-phenyl-2-pyrrolidones, and 1-phenyl-2-piperidones

Abstract

The rate coefficients for the alkaline hydrolysis of a series of substituted 1-phenylazetidin-2-ones, -2-pyrrolidones, and -2-piperidones, and N-methylacetanilides and N-methylformanilides in aqueous dimethyl sulphoxide and in aqueous dioxane or water have been measured at several temperatures. The reactions were first order in substrate and, for the lactams and acetanilides, first order in base and, for the formanilides, both first and second order in base. Hammett reaction constants and activation parameters have been evaluated for each system. The relative reactivity, salt, solvent and solvent isotope effects have been examined. The following mechanisms for the reactions are suggested. For the β-lactams, the pathway appears to be the rate-determining attack by hydroxide and, for the γ- and δ-lactams and acetanilides, rate-determining fission of the carbon–nitrogen link, which follows equilibrium addition of the base. The formanilides appear to form a tetrahedral intermediate with hydroxide which can collapse to product via rate-determining water- or base-catalysis.