Comparison of Aminolysis of 2‑Pyridyl and 4‑Pyridyl X‑Substituted Benzoates in Acetonitrile: Evidence for a Concerted Mechanism Involving a Cyclic Transition State

A kinetic study on reactions of 2-pyridyl X-substituted benzoates (<b>6a</b>–<b>i</b>) with a series of cyclic secondary amines in MeCN is reported. The Hammett plot for the reaction of <b>6a</b>–<b>i</b> with piperidine consists of two intersecting straight lines while the Yukawa–Tsuno plot exhibits an excellent linear correlation with ρ_X = 1.28 and <i>r</i> = 0.63, indicating that the nonlinear Hammett plot is not caused by a change in the rate-determining step but rather by resonance stabilization of substrates possessing an electron-donating group (EDG) in the benzoyl moiety. The Brønsted-type plots are linear with β_nuc = 0.59 ± 0.02, which is typical of reactions reported to proceed through a concerted mechanism. A cyclic transition state (TS), which forces the reaction to proceed through a concerted mechanism, is proposed. The deuterium kinetic isotope effect of 1.3 ± 0.1 is consistent with the proposed mechanism. Analysis of activation parameters reveals that Δ<i>H</i>^‡ increases linearly as the substituent X changes from an electron-withdrawing group (EWG) to an EDG, while <i>T</i>Δ<i>S</i>^‡ remains nearly constant with a large negative value. The constant <i>T</i>Δ<i>S</i>^‡ value further supports the proposal that the reaction proceeds through a concerted mechanism with a cyclic TS