Tetraisopropyl Titanate-Catalyzed Esterification Mechanism for the Synthesis of 1,2-Cyclohexanedicarboxylates

Abstract

Titanates (e.g., Ti(OiPr)4) serve as green, noncorrosive catalysts for synthesizing the new plasticizer bis(2-ethylhexyl) cyclohexane-1,2-dicarboxylate (DEHCH). However, the structural evolution of the Ti center and the microscopic mechanism remain elusive, hindering industrial process optimization. Herein, we used density functional theory (DFT), coupled with Atoms-in-Molecules (AIM) topological analysis and charge decomposition analysis (CDA), to investigate the diesterification mechanism. The reaction proceeds via four steps: alcoholysis/ligand exchange (ΔG = 36.46 kJ·mol–1); nucleophilic attack of the isooctyloxy group to form a tetrahedral intermediate (ΔG = 65.05 kJ·mol–1); proton transfer to form a tetrahedral geminal diol (ΔG = 36.46 kJ·mol–1); and intramolecular dehydration (ΔG = 156.28 kJ·mol–1). The lower ΔG of alcoholysis relative to the hydrolysis side reaction (48.27–69.74 kJ·mol–1) effectively mitigates water-induced catalyst deactivation. Notably, the Ti atom preferentially activates the isooctyloxy oxygen over the carboxylic carbonyl oxygen, dominating the subsequent nucleophilic attack. AIM and CDA results further reveal dynamic coordination behavior: the Ti center flexibly interconverts between geometries resembling a five-coordinate trigonal bipyramid and a six-coordinate regular octahedron, activating the carboxylic carbonyl oxygen via formation of a partial covalent Ti–O bond. These results suggest that an excess of 2-ethylhexanol (2-EH) not only promotes the desired esterification but also suppresses hydrolysis-induced catalyst deactivation.