Thermodynamics and Kinetics of Spiro-Heterocycle Formation Mechanism: Computational Study

Abstract

Reaction mechanism among indoline-2,3-dione, pyrrolidine-2-carboxylic acid and (Z)-2-(1-(2-hydroxynaphthalen-1-yl)ethylidene)hydroxycarboxamide to form 1'-((((aminooxy)carbonyl)amino)methyl)-2'-(1-hydroxynaphthalen-2-yl)-2'-methyl-1',2',5',6',7',7a'-hexahydrospiro[indoline-3,3'-pyrrolo[1,2-a]imidazole-2-one was investigated using density functional theory (DFT) at B3LYP basis theory. The three-step reaction occurred via five stationary points that include two van der Waals complexes (1 and 2), two intermediates and one transition state. The entropy change across the various steps indicated an appreciable interaction or overlap within the reacting molecules. This is evident in variations in the geometries of the optimized species as the reaction progressed from the intermediates through the transition state to the final product. The steps leading to the van der Waals complexes (1 and 2) formation were found to be thermodynamically feasible compare to the bimolecular transition step. From the equilibrium constant value, the transition step was found to be the rate-determining step. The study was able to provide information on the energy demand of the individual step of the reaction and the overall process in addition to change in geometry as the molecules undergo transformation to the final product.