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 <b>5a</b>–<b>i</b>. Plots of pseudo-first-order rate constants (<i>k</i>_obsd) vs [amine] curve upward for the reactions of substrates possessing a strong electron-withdrawing group in the benzoyl moiety (<b>5a</b>–<b>d</b>) but are linear for the reactions of those bearing an electron-donating group (<b>5e</b>–<b>i</b>), indicating that the electronic nature of substituent X governs the reaction mechanism. The <i>k</i>₁<i>k</i>₂/<i>k</i>_–1 and <i>k</i>₁<i>k</i>₃/<i>k</i>_–1 values were calculated from the intercept and slope of the linear plots of <i>k</i>_obsd/[amine] vs [amine], respectively. The Hammett plot for <i>k</i>₁<i>k</i>₂/<i>k</i>_–1 consists of two intersecting straight lines, while the Yukawa–Tsuno plot exhibits an excellent linear correlation with ρ_X = 0.41 and <i>r</i> = 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 <i>k</i>₂/<i>k</i>_–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 β_nuc = 0.98 and 0.79 for <i>k</i>₁<i>k</i>₂/<i>k</i>_–1 and <i>k</i>₁<i>k</i>₃/<i>k</i>_–1, respectively. The effect of amine basicity on the microscopic rate constants is also discussed

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

Kinetic Study on Michael-Type Reactions of β‑Nitrostyrenes with Cyclic Secondary Amines in Acetonitrile: Transition-State Structures and Reaction Mechanism Deduced from Negative Enthalpy of Activation and Analyses of LFERs

A kinetic study is reported for the Michael-type reactions of X-substituted β-nitrostyrenes (<b>1a</b>–<b>j</b>) with a series of cyclic secondary amines in MeCN. The plots of pseudo-first-order rate constant <i>k</i>_obsd vs [amine] curve upward, indicating that the reactions proceed through catalyzed and uncatalyzed routes. The dissection of <i>k</i>_obsd into <i>Kk</i>₂ and <i>Kk</i>₃ (i.e., the rate constants for the uncatalyzed and catalyzed routes, respectively) revealed that <i>Kk</i>₃ is much larger than <i>Kk</i>₂, implying that the reactions proceed mainly through the catalyzed route when [amine] > 0.01 M. Strikingly, the reactivity of β-nitrostyrene (<b>1g</b>) toward piperidine decreases as the reaction temperature increases. Consequently, a negative enthalpy of activation is obtained, indicating that the reaction proceeds through a relatively stable intermediate. The Brønsted-type plots for the reactions of <b>1g</b> are linear with β_nuc = 0.51 and 0.61, and the Hammett plots for the reactions of <b>1a</b>–<b>j</b> are also linear with ρ_X = 0.84 and 2.10 for the uncatalyzed and catalyzed routes, respectively. The reactions are concluded to proceed through six-membered cyclic transition states for both the catalyzed and uncatalyzed routes. The effects of the substituent X on reactivity and factors influencing β_nuc and ρ_X obtained in this study are discussed

A Kinetic Study on Nucleophilic Displacement Reactions of Aryl Benzenesulfonates with Potassium Ethoxide: Role of K⁺ Ion and Reaction Mechanism Deduced from Analyses of LFERs and Activation Parameters

Pseudofirst-order rate constants (<i>k</i>_obsd) have been measured spectrophotometrically for the nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates <b>4a</b>–<b>f</b> and Y-substituted phenyl benzenesulfonates <b>5a</b>–<b>k</b> with EtOK in anhydrous ethanol. Dissection of <i>k</i>_obsd into <i>k</i>_EtO^– and <i>k</i>_EtOK (i.e., the second-order rate constants for the reactions with the dissociated EtO^– and ion-paired EtOK, respectively) shows that the ion-paired EtOK is more reactive than the dissociated EtO^–, indicating that K⁺ ion catalyzes the reaction. The catalytic effect exerted by K⁺ ion (e.g., the <i>k</i>_EtOK/<i>k</i>_EtO^– ratio) decreases linearly as the substituent X in the benzenesulfonyl moiety changes from an electron-donating group (EDG) to an electron-withdrawing group (EWG), but it is independent of the electronic nature of the substituent Y in the leaving group. The reactions have been concluded to proceed through a concerted mechanism from analyses of the kinetic data through linear free energy relationships (e.g., the Brønsted-type, Hammett, and Yukawa–Tsuno plots). K⁺ ion catalyzes the reactions by increasing the electrophilicity of the reaction center through a cyclic transition state (TS) rather than by increasing the nucleofugality of the leaving group. Activation parameters (e.g., Δ<i>H</i>^‡ and Δ<i>S</i>^‡) determined from the reactions performed at five different temperatures further support the proposed mechanism and TS structures

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

Mechanistic Assessment of S_NAr Displacement of Halides from 1‑Halo-2,4-dinitrobenzenes by Selected Primary and Secondary Amines: Brønsted and Mayr Analyses

Pseudo-first-order rate constants (<i>k</i>_obsd) have been measured spectrophotometrically for nucleophilic substitution reactions of 1-X-2,4-dinitrobenzenes (<b>1a</b>–<b>d</b>, X = F, Cl, Br, I) with various primary and secondary amines in MeCN and H₂O at 25.0 ± 0.1 °C. The plots of <i>k</i>_obsd vs [amine] curve upward for reactions of <b>1a</b> (X = F) with secondary amines in MeCN. In contrast, the corresponding plots for the other reactions of <b>1b</b>–<b>d</b> with primary and secondary amines in MeCN and H₂O are linear. The Brønsted-type plots for reactions of <b>1a</b>–<b>d</b> with a series of secondary amines are linear with β_nuc = 1.00 for the reaction of <b>1a</b> and 0.52 ± 0.01 for those of <b>1b</b>–<b>d</b>. Factors governing reaction mechanisms (e.g., solvent, halogen atoms, H-bonding interactions, amine types) have been discussed. Kinetic data were also analyzed in terms of the Mayr nucleophilicity parameter for the amines with each aromatic substrate. Provisional Mayr electrophilicity parameter (<i>E</i>) values for 1-X-2,4-dinitrobenzenes have been determined: <i>E</i> = −14.1 for X = F, <i>E</i> = −17.6 for X = Cl and Br, and <i>E</i> = −18.3 for X = I. These values are consistent with the range and order of <i>E</i> values for heteroaromatic superelectrophiles and normal 6-π aromatic electrophiles