A Kinetic Study on Aminolysis of 2-Pyridyl X-Substituted Benzoates: Effect of Changing Leaving Group from 4-Nitrophenolate to 2-Pyridinolate on Reactivity and Mechanism

Abstract

Second-order rate constants (kN) have been measured spectrophotometrically for nucleophilic substitution reactions of 2-pyridyl X-substituted benzoates 8a-e with a series of alicyclic secondary amines in H2O at 25.0 ± 0.1 oC. The kN values for the reactions of 8a-e are slightly smaller than the corresponding reactions of 4-nitrophenyl X-substituted benzoates 1a-e (e.g., kN1a-e/kN8a-e = 1.1 ~ 3.1), although 2-pyridinolate in 8a-e is ca. 4.5 pKa units more basic than 4-nitro-phenolate in 1a-e. The Brønsted-type plot for the aminolysis of 8c (X = H) is linear with βnuc = 0.77 and R2 = 0.991 (Figure 1), which is typical for reactions reported previously to proceed through a stepwise mechanism with break-down of a zwitterionic tetrahedral intermediate T ± being the rate-determining step (RDS), e.g., aminolysis of 4-nitro-phenyl benzoate 1c. The Hammett plot for the reactions of 8a-e with piperidine consists of two intersecting straight lines (Figure 2), i.e., ρ = 1.71 for substrates possessing an electron-donating group (EDG) while ρ = 0.86 for those bearing an electron-withdrawing group (EWG). Traditionally, such a nonlinear Hammett plot has been interpreted as a change in RDS upon changing substituent X in the benzoyl moiety. However, it has been proposed that the nonlinear Hammett is not due to a change in RDS since the corresponding Yukawa-Tsuno plot exhibits excellent linear correla-tion with ρ = 0.85 and r = 0.62 (R2 = 0.995, Figure 3). Stabilization of substrates 8a-e in the ground state has been con-cluded to be responsible for the nonlinear Hammett plot