Strain effects in acyl transfer reactions. Part III. Hydroxide and buffer-catalysed hydrolysis of small and medium ring lactones

Abstract

Second-order rate constants for the alkaline hydrolyses of lactones and esters at 319 K decrease in the order methyl formate > δ-valerolactone > β-propiolactone > γ-butyrolactone, ε-caprolactone > methyl acetate. The enhanced reactivity of the δ-lactone is due to a reduction in enthalpy of activation but the β-lactone derives its extra reactivity solely from a favourable increase in the entropy of activation for B_AC2 hydrolysis. Only the β-lactone exhibits detectable activity towards either pyridine or 1-methylimidazole in aqueous solution. For both amines, nucleophilic substitution with alkyl oxygen fission proceeds faster than attack at the acyl centre and results in the formation of a betaine as the major product. No reactivity could be detected for either amine with methyl formate or δ-valerolactone. It thus appears that conformational orientation factors are capable of accelerating the reaction of the ester group with strong nucleophiles whereas angle-strain effects become more important for weaker ones.