Studies on the hydrolysis of 3,1-benzoxazin-4-ones

Abstract

The hydrolysis of 2-methyl-3,1-benzoxazin-4-one (I) obeys the rate law k=(31·6 ± 0·5)a_H++(56·2 ± 0·9)[OH^–] in dilute buffers at 25° and 0·1M ionic strength. In deuterium oxide solvent the rate law is k=(31·6 ± 1·5)a_D⁺+(10·0 ± 0·05)[OD^–]. The basic components of the buffers exerted a catalytic effect and the derived second-order rate constants obeyed a Brønsted relationship with exponent 0·67. The term for imidazole was of the same order of magnitude as that for phosphate, indicating general base catalysis by imidazole; the solvent deuterium isotope effect on the hydroxide ion term indicated general base catalysis. The reaction with azide ion was nucleophilic but did not yield hydrolysis products. Hydrolysis under acidic and basic conditions in oxygen-18 enriched water revealed that attack took place at C-2 and C-4, respectively. Hydrolysis of compound (I) in basic deuterium oxide gave product with no deuterium incorporation in the acetyl group, indicating the absence of an E1cB mechanism. Substituted 2-phenyl-3,1-benzoxazin-4-ones (II) showed Hammett ρ values under acidic and basic conditions of hydrolysis (–0·38 and +0·71) consistent with the foregoing cleavage patterns. Strongly acidic media inhibited hydrolysis of the phenyl and p-methoxyphenyl derivatives in accord with extensive protonation of N-1 and a lowering of the water activity with increase in acidity.