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 (<TEX>$k_N$</TEX>) have been measured spectrophotometrically for nucleophilic substitution reactions of 2-pyridyl X-substituted benzoates 8a-e with a series of alicyclic secondary amines in <TEX>$H_2O$</TEX> at <TEX>$25.0{\pm}0.1^{\circ}C$</TEX>. The <TEX>$k_N$</TEX> values for the reactions of 8a-e are slightly smaller than the corresponding reactions of 4-nitrophenyl X-substituted benzoates 1a-e (e.g., <TEX>$kN^{1a-e}/k_N^{8a-e}$</TEX> = 1.1 ~ 3.1), although 2-pyridinolate in 8a-e is ca. 4.5 <TEX>$pK_a$</TEX> units more basic than 4-nitrophenolate in 1a-e. The Br<TEX>$\o$</TEX>nsted-type plot for the aminolysis of 8c (X = H) is linear with <TEX>$\beta_{nuc}$</TEX> = 0.77 and <TEX>$R^2$</TEX> = 0.991 (Figure 1), which is typical for reactions reported previously to proceed through a stepwise mechanism with breakdown of a zwitterionic tetrahedral intermediate <TEX>$T^{\pm}$</TEX> being the rate-determining step (RDS), e.g., aminolysis of 4-nitrophenyl benzoate 1c. The Hammett plot for the reactions of 8a-e with piperidine consists of two intersecting straight lines (Figure 2), i.e., <TEX>$\rho$</TEX> = 1.71 for substrates possessing an electron-donating group (EDG) while <TEX>$\rho$</TEX> = 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 correlation with <TEX>$\rho$</TEX> = 0.85 and r = 0.62 (<TEX>$R^2$</TEX> = 0.995, Figure 3). Stabilization of substrates 8a-e in the ground state has been concluded to be responsible for the nonlinear Hammett plot.