Hydrolysis of 1-(X-substituted-benzoyl)-4-aminopyridinium ions: effect of substituent X on reactivity and reaction mechanism

Abstract

A kinetic study is reported for hydrolysis of 1-(X-substituted-benzoyl)-4-aminopyridinium ions 2a–i, which were generated in situ from the nucleophilic substitution reaction of 2,4-dinitrophenyl X-substituted-benzoates 1a–i with 4-aminopyridine in 80 mol% H₂O/20 mol% DMSO at 25.0 ± 0.1 °C. The plots of pseudo-first-order rate constants k_obsdvs.pyridine concentration are linear with a large positive intercept, indicating that the hydrolysis of 2a–i proceeds through pyridine-catalyzed and uncatalyzed pathways with the rate constant k_cat and k_o, respectively. The Hammett plots for k_cat and k_o consist of two intersecting straight lines, which might be taken as evidence for a change in the rate-determining step (RDS). However, it has been proposed that the nonlinear Hammett plots are not due to a change in the RDS but are caused by stabilization of 2a–i in the ground state through a resonance interaction between the π-electron-donor substituent X and the carbonyl functionality. This is because the corresponding Yukawa-Tsuno plots exhibit excellent linear correlations with ρ_X = 1.45 and r = 0.76 for k_cat while ρ_X = 1.39 and r = 0.72 for k_o. A possibility that the hydrolysis of 2a–i proceeds through a concerted mechanism has been ruled out on the basis of the large ρ_X values. Thus, the reaction has been concluded to proceed through a stepwise mechanism in which the leaving group departs after the RDS since OH⁻ is more basic and a poorer nucleofuge than 4-aminopyridine.