An E1cB mechanism for the alkaline hydrolysis of thiolesters of fluorene-9-carboxylic acid: effect of ester conjugate base structure on differential eliminative reactivity of oxygen and sulphur nucleofuges

Abstract

The alkaline hydrolysis of a series of thiolesters of fluorene-9-carboxylic acid has been studied and pseudo-first-order rate constants, k_obs(hydroxide ion in excess), showed saturation with respect to hydroxide ion concentration for any given ester. The kinetic expression describing such behaviour was found to be k_obs=k′/(1 +K_w/K_a[HO^–]) where k′ is the limiting rate constant at high base concentrations and K_a is the acid dissociation constant of the acidic ester. Values of log₁₀k′ followed a Brønsted correlation (with the pK_a of the conjugate acid of the appropriate leaving group) with equation log₁₀k′= 6.10 – 1.14 pK_1.g. (r 0.9700). There was no significant steric effect on k′ as the 2′-methoxythiophenyl ester obeyed the above relationship. Esters with poorer leaving groups (S-benzyl, S-n-propyl) deviated positively from the correlation. For active thiolesters of fluorene-9-carboxylic acid the highly negative value of β_1.g. for the k′ term (slope of the Brønsted plot), along with the saturation kinetics and a positive/zero value (+4.6 ± 6.1 J K^–1 mol^–1) for the entropy of activation for the S-phenyl ester was evidence of an E1cB alkaline hydrolytic mechanism. In support of this were the low solvent deuterium kinetic solvent isotope effect on k′(k_H/k_D= 1.37) and the rate inhibition on 9-methylation. Comparison of fluorene-9-esters with acetoacetic esters showed that there was less difference in reactivity between oxygen and sulphur esters for the former, an effect explained as lying in the highly delocalised nature of the fluorene ester conjugate bases.