DFT study of the acid‐catalyzed esterification reaction mechanism of methanol with carboxylic acid and its halide derivatives

Abstract Extensive experimental studies have been dedicated to the esterification mechanisms from carboxylic acids and acid halides. However, attention on the theoretical aspect of the mechanism has been scarcely addressed. Herein, the acid‐catalyzed esterification mechanism of methanol with acetic acid and its halide derivatives is described using density functional theoretical method and solvation model based on density. The mechanistic investigation involved formation of cyclic prereaction and 6‐membered ring transition structures, which favors the esterification process and product formation. A good comparison with experimental data from literature for the esterification reaction of acetic acid with methanol was achieved through this in silico approach. Density Functional Theory‐based quantum descriptors were applied to provide a better understanding on the reactivity, selectivity, and stability of this reaction. This theoretical results provide a crucial guide to study classical acid‐catalyzed reaction mechanisms and applying a reasonable theoretical model to study similar organic reactions. In addition, it can be applied to larger systems such as enzymatic mechanism.