E1cB mechanisms. Part III. Effect of ionisation of amido-NH on reaction of hydroxide ion with methyl 3- and 4-benzamidobenzoates

Abstract

Rate constants for hydrolysis of methyl 4-(substituted benzamido)benzoates and the corresponding 3-isomers have been measured over a range of hydroxide-ion concentrations (20% dioxan–water, v/v) spanning the ionisation of the amido-NH group. The pseudo-first-order rate constants obeyed a kinetic law (i) derived from a mechanism, k=k₂{1 +(K_a/K_w)(k₄/k₂)[OH^–]}[OH^–]/(1 +(K_a/K_w)[OH^–])(i) involving bimolecular attack (B_Ac2) of hydroxide ion on both neutral and ionised ester. Neutral ester reacted five times more rapidly than conjugate base with hydroxide ion. Ionisation of the amido-NH functions were measured separately by spectrophotometric titration and the pK_a values varied from 12 to 14·5. Values of K_a for the methyl 4-(substituted benzamido)benzoates and the 3-isomers had Hammett sensitivities of +1·53 (r= 0·999) and +1·37 (r= 0·993) respectively. Sensitivity of k₂ and k₄(hydroxide on neutral ester and hydroxide on conjugate base respectively) to Hammett σ values were very small, in agreement with other workers' results for sensitivities for ionisation of substituted benzamidophenols and anilines.