Computational Study of Reaction Mechanisms in Organic Chemical Reactions

Abstract

Computational chemistry has emerged as a transformative approach for elucidating mechanistic pathways in organic reactions where direct experimental observation of transition states remains experimentally inaccessible. This study computationally investigates five fundamental organic reactions SN2 nucleophilic substitution, E2 elimination, Diels-Alder cycloaddition, aldol condensation, and acid-catalyzed esterification employing Density Functional Theory (DFT) at the B3LYP/6-311+G(d,p) level using Gaussian 16 software. The principal objectives are to determine activation energies, characterize transition state geometries, and compare frontier molecular orbital (HOMO-LUMO) parameters as reactivity predictors across mechanistically distinct reactions. The central hypothesis is that DFT computed at B3LYP/6-311+G(d,p) predicts experimental activation barriers within ±2.5 kcal/mol. Results from six data tables reveal activation barriers between 12.6 and 24.5 kcal/mol, HOMO-LUMO gaps ranging from 3.31 to 4.23 eV, and Natural Bond Orbital (NBO) charge distributions consistent with established mechanistic frameworks. Functional benchmarking confirms that ωB97XD achieves the lowest mean absolute deviation of 1.1 kcal/mol. These findings validate DFT as a quantitatively reliable mechanistic tool with direct implications for pharmaceutical design and synthetic strategy.