Nucleophilic Substitution Reactions of Thiophenyl 4-Nitrobenzoates with Pyridines in Acetonitrile

Abstract

The kinetics of reactions between Z-thiophenyl 4-nitrobenzoates and X-pyridines in acetonitrile at 55.0 degrees C are investigated. The Brönsted plots obtained for the pyridinolysis of thiophenyl benzoates are curved, with the center of curvature at pK(a) approximately 4.2 (pK(a)(0)). The Brönsted plots for these nucleophilic reactions show a change in slope from a large (beta(X) congruent with 0.64-0.72) to a small (beta(X) congruent with 0.19-0.23) value, which can be attributed to a change in the rate-determining step from breakdown to formation of a tetrahedral intermediate in the reaction path as the basicity of the pyridine nucleophile increases. This mechanism is supported by the change of the cross-interaction constant rho(XZ) from a large positive (rho(XZ) = 1.41) for the weakly basic pyridines to a small negative (rho(XZ) = -0.32) value for the strongly basic pyridines. The reactivity-selectivity principle (RSP) holds for the rate-limiting breakdown but fails for the formation of the intermediate. The aminolysis of thiophenyl benzoate with deuterated 4-chlorobenzylamine catalyzed by glymes has primary deuterium kinetic isotope effects (PKIEs), k(H(cat))/k(D(cat)) congruent with 1.28-1.62.

Kinetics and mechanism of the aminolysis ofO-ethylS-aryl thiocarbonates in acetonitrile

“…We note that the magnitudes of these selectivity parameters are in general considerably smaller than those for the aminolysis with benzylamines involving rate-limiting expulsion of the leaving group, ArSϪ, from a tetrahedral intermediate, T Ϯ . For example, for the aminolysis of thiolphenyl benzoates (structure I with R ϭ Ph) with benzylamines in acetonitrile [11], which is believed to proceed by a stepwise mechanism with rate-limiting breakdown T Ϯ , the magnitude of X (␤ X ) and Z (␤ Z ) values were much larger with Ϫ1.88 (1.86) and 3.84 Table I. The ␤ X value of 0.63 obtained in the present work is similar to those for the concerted reaction of structure (R ϭ EtO) with alicyclic (secondary) amines [7,8] (␤ X ϭ 0.56 for Ar ϭ 2,4-(NO 2 ) 2 C 6 H 3 and ␤ X ϭ 0.48 for Ar ϭ 2,4,6-(NO 2 ) 2 C 6 H 2 in structure I) in aqueous solution.…”

“…The failure of the RSP also supports the proposed concerted mechanism [17,18]. We therefore conclude that the aminolysis of thiophenyl derivatives, structure I (R ϭ EtO), is enforced to proceed through a concerted mechanism due to destabilization of the putative tetrahedral intermediate, T Ϯ , (i) by a strong electron releasing power of the R group (R ϭ EtO has a stronger electron-releasing effect ( R ϭ Ϫ0.50) than R ϭ Me ( R ϭ Ϫ0.18)) [21]; (ii) by a strong "push" provided by a primary amine in T Ϯ (the push provided by amines in the putative intermediate, T Ϯ , decreases in the order, primary Ͼ secondary Ͼ tertiary due to stabilization provided by the cationic charge dispersion by the amines within T Ϯ ) [11]; (iii) by a relatively strong leaving ability of the ArS group (lower pK a than the corresponding ArO group), and (iv) by a destabilizing effect of T Ϯ by the solvent, acetonitrile [3].…”

“…Quite interestingly, however, concerted processes are found only in the reactions between O-ethyl S-aryl-thiocarbonates (structure I with R ϭ EtO) with good leaving groups (Ar ϭ 2,4-(NO 2 ) 2 -and 2,4,6-(NO 2 ) 3 -C 6 H 2 ) and alicyclic secondary amines (␤ nuc ϭ 0.4 ϳ 0.6) [7,8]. The concerted mechanism has been shown to be enforced by (i) instability incurred by the ArS group because ArSϪ is much less basic than ArOϪ and a better nucleofuge from T Ϯ than ArOϪ group [4]; (ii) stronger push provided by EtO, which enhances the nucleofugality of both the amine and arylthiolate ion from the intermediate relative to other R groups [9 -11] (e.g., phenyl and alkyl); (iii) much faster expulsions of a given amine and ArSϪ from T Ϯ formed with structure I than those from T Ϯ with structures II and/or III due to a stronger -bonding energy of the carbonyl group compared with thiocarbonyl [9]; and (iv) greater "push" to expel ArSϪ from T Ϯ provided by the secondary (alicyclic) amines than the tertiary (pyridines) amines [11].…”

Kinetics and mechanism of the aminolysis of thiophenyl methylacetates in acetonitrile

“…This means that the observed ␤ X (␤ nuc ) ϭ 1.2 ϳ 2.5 for the aminolysis with benzylamines lead to the ␤ Ϫa (ϭ dlog k Ϫa / dpK a (X)) value of Ϫ0.9 ϳ Ϫ2.2 [ϭ (0.2 ϳ 0.3) Ϫ (1.2 ϳ 2.5)]. The pK a o was lower for pyridines than for alicyclic amines under the same reaction conditions due to the lower k Ϫa , whereas it was lower for a more delocalized phenolate ion (2,4,6-trinitrophenolate ion) expulsion due to the higher k b value [8,20]. Thus the loss of a strong localized cationic charge on the nitrogen atom of benzylammonium ion in the T Ϯ is so large that the benzylamine expulsion rates from T Ϯ are 2 ϳ 3 times more sensitive to the substituent variation in the benzylamine than the sensitivity of aniline expulsion rates from the corresponding T Ϯ to the substituent charge in the aniline.…”

Kinetics and Mechanism of the Aminolysis of O-Methyl S-Aryl Thiocarbonates in Acetonitrile

“…For example, for the aminolysis of thiophenyl benzoates (structure 2 with R = Ph) with benzylamines in acetonitrile, 7 which is believed to proceed by a stepwise mechanism with rate-limiting breakdown T ± , the magnitude of ρ X (β X ) and ρ Z (β Z ) values were much larger with −1.88 (1.86) and 3.84 (−1.63) for Z = H and X = H, respectively. These are larger by ca.…”