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

Evidence for a Catalytic Six-Membered Cyclic Transition State in Aminolysis of 4‑Nitrophenyl 3,5-Dinitrobenzoate in Acetonitrile: Comparative Brønsted-Type Plot, Entropy of Activation, and Deuterium Kinetic Isotope Effects

A kinetic study for reactions of 4-nitrophenyl 3,5-dinitrobenzoate (<b>1a</b>) with a series of cyclic secondary amines in acetonitrile is reported. Plots of the pseudo-first-order rate constant (<i>k</i>_obsd) vs [amine] curve upward, while those of <i>k</i>_obsd /[amine] vs [amine] exhibit excellent linear correlations with positive intercepts, indicating that the reaction proceeds through both uncatalyzed and catalyzed routes. Brønsted-type plots for uncatalyzed and catalyzed reactions are linear with β_nuc = 1.03 and 0.69, respectively. The Δ<i>H</i>^⧧ and Δ<i>S</i>^⧧ values measured for the catalytic reaction with morpholine are −0.80 kcal/mol and −61.7 cal/(mol K), respectively. The negative Δ<i>H</i>^⧧ with a large negative Δ<i>S</i>^⧧ suggests that the reaction proceeds through a highly ordered transition state (i.e., a six-membered cyclic transition state, which includes a second amine molecule that accepts a proton from the aminium moiety of the zwitterionic tetrahedral intermediate and simultaneously donates a proton to the aryloxyl oxygen of the nucleofuge with concomitant C–OAr bond scission). This proposal is consistent with the smaller β_nuc value for the catalyzed reaction as compared to the uncatalyzed reaction. An inverse deuterium kinetic isotope effect (DKIE) value of 0.93 and a contrasting normal primary DKIE value of 3.23 for the uncatalyzed and catalyzed routes, respectively, also support the proposed cyclic transition state