N-hydroxy-compounds as acyl transfer agents. Part 2. Kinetics and mechanism of hydrolysis and aminolysis of 1-hydroxypyrazole and 1-hydroxyimidazole esters

Abstract

Benzoate esters of 3-(alkyl or aryl)-1-hydroxy-4,5-dimethylpyrazole (1) and 1-hydroxy-4,5-dimethyl-2-phenylimidazole (2) react with hydroxide ion, water (via acid catalysis), and primary amines in aqueous dioxan at 25°, but at a much slower rate than the corresponding esters of 1-hydroxybenzotriazole, pydrolysis of the pyrazole esters (1 a and b) shows specific acid and base catalysis, giving Hammett ρ values of 1.1 and 1.5 respectively. For the acid-catalysed process, protonation of the heterocyclic ring rather than the carbonyl oxygen is invoked. Acidcatalysed hydrolysis of the imidazole ester (2a) occurs at about the same rate, but the hydroxide ion-catalysed process is much slower (k_OH^– 8.32 l mol^–1 s^–1). The rate of hydroxide attack on (1a and b) and (2a) has a lower sensitivity to the pK_a of the leaving group (β_1˙g˙–0.2), than phenyl acetates (β_1˙g˙–0.33). Only one pK_a(7.22) could be measured for (le), in contrast to two pK_a values reported previously (6.1 and 5.5). The reaction of (1 a) with primary amines gives β_nuc0.89, and general base catalysis was observed with ethylenediamine monocation and glycine ethyl ester (k_gb= 61.6 × 10^–3 l² mol^–2 s^–1 and 5.3 × 10^–3 l² mol^–3 s^–1). With amines the imidazole ester (2a) shows β_nuc 0.80 and no general base-catalysed process was observed. Above pH 9, 2-phenyloxazolin-5-one (12) was observed as an intermediate in the hydrolysis and aminolysis of the hippurate ester (1c). The ester (1d) reacts with nucleophiles by a B_AC2 mechanism at all pH. Compounds (1e and 1f) and (2b) and 1hydroxybenzotriazole catalyse the decomposition of p-nitrophenyl acetate, but the latter two compounds show a 50-fold negative deviation from structure–reactivity correlations (log k_nversus pK_a).