Mechanistic investigation of the uncatalyzed esterification reaction of acetic acid and acid halides with methanol: a DFT study

Implementation of catalysts to drive reactions from reactants to products remains a burden to synthetic and organic chemists. In spite of investigations into the kinetics and mechanism of catalyzed esterification reactions, less effort has been made to explore the possibility of an uncatalyzed esterification process. Therefore, a comprehensive mechanistic perspective for the uncatalyzed mechanism at the molecular level is presented. Herein, we describe the non-catalyzed esterification reaction of acetic acid and its halide derivatives (XAc, where X= OH, F, Cl, Br, I) with methanol (MeOH) through a concerted process. The reaction in vacuum and methanol was performed using the density functional theory (DFT) method at M06-2X level with def2-TZVP basis set after a careful literature survey and computations. Esterification through cyclic 4- or 6-membered transition state structures in one- or two-step concerted mechanisms were investigated. The present study outlines the possible cyclic geometry conformations that may occur during experiments at simple ratio of reactants. The free energy of activation for acetic acid and acetyl chloride are 36 kcal mol−1 and 21 kcal mol−1, respectively. These are in good agreement with available experimental results from the literature. The selected quantum chemical descriptors proved to be useful tools in chemical reactivity prediction for the reaction mechanism. This quantum mechanics study can serve as a necessary step towards revisiting uncatalyzed reaction mechanisms in some classical organic reactions.