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 (1a) with a series of cyclic secondary amines in acetonitrile is reported. Plots of the pseudo-first-order rate constant (kobsd) vs [amine] curve upward, while those of kobsd /[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 ßnuc = 1.03 and 0.69, respectively. The ΔH(⧧) and ΔS(⧧) values measured for the catalytic reaction with morpholine are -0.80 kcal/mol and -61.7 cal/(mol K), respectively. The negative ΔH(⧧) with a large negative ΔS(⧧) 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 ßnuc 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.

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 (6a-i) with a series of cyclic secondary amines in MeCN is reported. The Hammett plot for the reaction of 6a-i with piperidine consists of two intersecting straight lines while the Yukawa-Tsuno plot exhibits an excellent linear correlation with ρX = 1.28 and r = 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 ßnuc = 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 ΔH(‡) increases linearly as the substituent X changes from an electron-withdrawing group (EWG) to an EDG, while TΔS(‡) remains nearly constant with a large negative value. The constant TΔS(‡) value further supports the proposal that the reaction proceeds through a concerted mechanism with a cyclic TS.

Electronic nature of substituent X governs reaction mechanism in aminolysis of 4-pyridyl X-substituted-benzoates in acetonitrile.

A kinetic study is reported for aminolysis of 4-pyridyl X-substituted-benzoates 5a-i. Plots of pseudo-first-order rate constants (k(obsd)) vs [amine] curve upward for the reactions of substrates possessing a strong electron-withdrawing group in the benzoyl moiety (5a-d) but are linear for the reactions of those bearing an electron-donating group (5e-i), indicating that the electronic nature of substituent X governs the reaction mechanism. The k(1)k(2)/k(-1) and k(1)k(3)/k(-1) values were calculated from the intercept and slope of the linear plots of k(obsd)/[amine] vs [amine], respectively. The Hammett plot for k(1)k(2)/k(-1) consists of two intersecting straight lines, while the Yukawa-Tsuno plot exhibits an excellent linear correlation with ρ(X) = 0.41 and r = 1.58, implying that the nonlinear Hammett plot is not due to a change in rate-determining step but is caused by stabilization of substrates possessing an electron-donating group through resonance interactions. The small ρ(X) suggests that the k(2)/k(-1) ratio is little influenced by the nature of substituent X. The Brønsted-type plots for aminolysis of 4-pyridyl 3,5-dinitrobenzoate 5a are linear with ß(nuc) = 0.98 and 0.79 for k(1)k(2)/k(-1) and k(1)k(3)/k(-1), respectively. The effect of amine basicity on the microscopic rate constants is also discussed.

Aminolysis of Y-substituted-phenyl 2-methoxybenzoates in acetonitrile: effect of the o-methoxy group on reactivity and reaction mechanism.

Second-order rate constants (k(N)) were measured for aminolyses of Y-substituted-phenyl 2-methoxybenzoates 2a-i and 4-nitrophenyl X-substituted-benzoates 3a-j in MeCN at 25.0 °C. The Brønsted-type plot for the reactions of 2a-i with piperidine curves downward, indicating that a change in rate-determining step (RDS) occurs. The Hammett plot for the reactions of 3a-j with piperidine consists of two intersecting straight lines, which might be taken as evidence for a change in RDS. However, the nonlinear Hammett plot has been suggested not to be due to a change in RDS but rather to the stabilization of the ground state of substrates possessing an electron-donating group (EDG) (e.g., 3a-c) through a resonance interaction, since the corresponding Yukawa-Tsuno plot exhibits an excellent linear correlation with ρ = 0.54 and r = 1.54. The ρ value found for the reactions of 3a-j in MeCN is much smaller than that reported previously for the corresponding reactions in H(2)O (i.e., ρ = 0.75). It is proposed that the reactions of 3a-j in MeCN proceed through a forced concerted mechanism due to instability of T(±) in the aprotic solvent, while the reactions of 2a-i proceed through a stepwise pathway with a stabilized T(±) through an intramolecular H-bonding interaction.