Kinetics and Mechanism of the Pyridinolysis of S-4-Nitrophenyl 4-Substituted Thiobenzoates in Aqueous Ethanol

Abstract

The pyridinolysis of S-4-nitrophenyl 4-X-substituted thiobenzoates (X = H, Cl, and NO2; 1, 2, and 3, respectively) is studied kinetically in 44 wt % ethanol-water, at 25.0 degrees C and an ionic strength of 0.2 M (KCl). The reactions are measured spectrophotometrically (420-425 nm) by following the appearance of 4-nitrobenzenethiolate anion. Pseudo-first-order rate coefficients (kobsd) are obtained throughout, under excess of amine over the substrate. Plots of kobsd vs [free amine] at constant pH are linear with the slope (kN) independent of pH. The Brnsted-type plot (log kN vs pKa0 of the conjugate acids of the pyridines) for the reactions of thiolbenzoate 1 is curved with a slope at high pKa, beta1 = 0.20, and slope at low pKa0, beta2 = 0.94. The pKa value for the center of the Brnsted curvature is pKa0 = 9.7. The pyridinolysis of thiolbenzoates 2 and 3 show linear Brnsted-type plots of slopes 0.94 and 1.0, respectively. These results and other evidence indicate that these reactions occur with the formation of a zwitterionic tetrahedral intermediate (T+/-). For the pyridinolysis of thiolbenzoate 1, breakdown of T+/- to products (k2 step) is rate-limiting for weakly basic pyridines and T+/- formation (k1 step) is rate-determining for very basic pyridines. The k2 step is rate-limiting for the reactions of thiolbenzoates 2 and 3. The smallest pKa0 value for the reaction of 1 is due to the weakest electron withdrawal of H (relative to Cl and NO2) in the acyl group, which results in the smallest k-1/k2 ratio. The pKa0 values for the title reactions are smaller than those for the reactions of secondary alicyclic amines with thiolbenzoates 1-3. This is attributed to a lower leaving ability from the T+/- of pyridines than isobasic alicyclic amines. The lower p value found for the pyridinolysis of 2,4-dinitrophenyl benzoate (pKa0 = 9.5), compared with that for the pyridinolysis of 1, is explained by the greater nucleofugality from T+/- of 2,4-dinitrophenoxide than 4-nitrobenzenethiolate, which renders the k-1/k2 ratio smaller for the reactions of the benzoate relative to thiolbenzoate 1. The title reactions are also compared with the aminolysis of similar thiolbenzoates in other solvents to assess the solvent effect.

Nucleophilic substitution reactions of diethyl 4‐nitrophenyl phosphate triester: Kinetics and mechanism

“…The p K a values for the phenols, SA amines, and pyridines were taken from 28–30. These p K a values were determined spectrophotometrically by the reported method 31.…”

Aminolysis of 2,4‐Dinitrophenyl X‐Substituted Benzoates and Y‐Substituted Phenyl Benzoates in MeCN: Effect of the Reaction Medium on Rate and Mechanism

“…For the pyridinolysis of 2,4‐dinitophenyl X‐substituted benzoates (X=H, 4‐Cl, and 4‐NO 2 ) in 44 % aqueous ethanol, Castro et al demonstrated that the Brønsted‐type plot is downwardly curved for the reactions of unsubstituted benzoate, but linear for the corresponding reactions of 4‐chloro and 4‐nitro derivatives 10. More recently, the p${K{{0\hfill \atop {\rm a}\hfill}}}$ value has been reported to increase from 9.7 to 9.9 and >10 as the substituent X changes from H to 4‐Cl and 4‐NO 2 , respectively, for the pyridinolysis of ( S )‐4‐nitrophenyl X‐substituted thiobenzoates in 44 % aqueous ethanol 11. Thus, Castro et al concluded that the p${K{{0\hfill \atop {\rm a}\hfill}}}$ value increases as the substituent X in the nonleaving group is substituted for a stronger electron‐withdrawing group 11.…”

“…More recently, the p${K{{0\hfill \atop {\rm a}\hfill}}}$ value has been reported to increase from 9.7 to 9.9 and >10 as the substituent X changes from H to 4‐Cl and 4‐NO 2 , respectively, for the pyridinolysis of ( S )‐4‐nitrophenyl X‐substituted thiobenzoates in 44 % aqueous ethanol 11. Thus, Castro et al concluded that the p${K{{0\hfill \atop {\rm a}\hfill}}}$ value increases as the substituent X in the nonleaving group is substituted for a stronger electron‐withdrawing group 11. This argument is consistent with the conclusion drawn by Gresser and Jencks from reactions of diaryl carbonates with quinuclidines 12.…”

Kinetics and mechanism of the anilinolysis of S‐aryl N‐arylthiocarbamates in acetonitrile

“…[34,35] For example, aminolyses of S-aryl-, [1] 4, S-aryl N-ethyl-, [2] 5, and p-nitrophenyl N-aryl carbamates, [3] 1, with benzylamines in acetonitrile were found to proceed by a concerted mechanism, while pyridinolyses of many aryl esters and carbonates are reported to proceed by a stepwise mechanism through a zwitterionic tetrahedral intermediate. [36][37][38][39][40][41][42][43] Anilines destabilize the tetrahedral intermediate relative to pyridines but stabilize it compared with benzylamines. The nucleofugality of anilines from T AE being intermediate between the two extremes, mechanistic changes can occur readily when Table 3.…”