Free Energy Profile of the Reaction between the Hydroxide Ion and Ethyl Acetate in Aqueous and Dimethyl Sulfoxide Solutions:  A Theoretical Analysis of the Changes Induced by the Solvent on the Different Reaction Pathways

Abstract

An extensive analysis of the free energy profile for the reaction of the hydroxide ion with ethyl acetate in both aqueous and dimethyl sulfoxide (DMSO) solutions has been carried out using ab initio calculations and including the solvent effect by the polarizable continuum model. Different reaction pathways were investigated, such as the usual B AC 2 mechanism, the carbanion mechanism, the elimination mechanism, and the S N 2 mechanism. Our calculation agrees with the view that in aqueous and DMSO solution basic hydrolysis occurs by the B AC 2 mechanism. In water, the predicted activation free energy value is 17.6 kcal mol -1 , which is in very good agreement with the experimental value of 18.8 kcal mol -1 . Using a new parametrization of the polarizable continuum model adequate to describe anions and neutral species in DMSO, the present study predicts a rate enhancement by a factor of 435 in the reaction when going from water (protic solvent) to DMSO (dipolar aprotic solvent). In this solvent, the activation free energy is predicted to drop to 14.0 kcal mol -1 . Furthermore, our results point out that the elimination mechanism is only 6.0 kcal mol -1 (∆G sol q ) 20.0 kcal mol -1 ) less favorable than the B AC 2 mechanism in DMSO solution, and 8.4 kcal mol -1 less favorable in water. The S N 2 and the carbanion mechanisms have barriers above 30 kcal mol -1 in water and DMSO and are thus highly unfavorable. These results suggest the elimination mechanism can become the dominant pathway in the basic hydrolysis of sterically crowded esters at the carbonyl center.

The role of nonelectrostatic solvation to chemical reactions in liquid phase

“…G nel = G cav + G dr (2) An important question to be analyzed is the level of importance of each nonelectrostatic term. It is known that both nonelectrostatic contributions can be relatively large and have opposite signals, leading to a small G nel .…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] Usually, the electrostatic solute-solvent interaction is the most important contribution of the solvent to the free energy of solvation ( G el ), mainly in polar media and in situations where ionic species are involved. The nonelectrostatic contribution ( G nel ) is regarded as playing a minor role, but it is important for a fine turning of the solvation process modeling.…”

Modelos contínuos do solvente: fundamentos

“…Esta falha do modelo se deve a interações específi-cas soluto-solvente, não descritas no modelo contínuo. Para modelar este efeito, é necessário definir cavidades que dependam do solvente e, em certos casos, incluir algumas moléculas explícitas do solvente, de forma que a especificidade da interação solutosolvente seja incluída 2,68,70,71 .…”

Influence of a β-OH substituent on SN2 reactions of fluoroethane: Intramolecular hydrogen bonding catalysis or inhibition? A theoretical study

“…Since most S N 2 reactions occur in solution, a large number of these studies have been devoted to the solvent effects [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. One of these effects that has been broadly examined is H-bonding via protic solvents that lowers the energy of an anionic nucleophile relative to the transition state, in which the charge is more diffuse, and results in an increase of activation energy [1,2].…”