Mechanism and rate constant of proline-catalysed asymmetric aldol reaction of acetone and p-nitrobenzaldehyde in solution medium: Density-functional theory computation

In search of new ways to improve catalyst design, the current research focused on using quantum mechanical descriptors to investigate the effect of proline as a catalyst for mechanism and rate of asymmetric aldol reaction. A plausible mechanism of reaction between acetone and 4-nitrobenzaldehyde in acetone medium was developed using highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies calculated via density functional theory (DFT) at the 6-31G∗/B3LYP level of theory. New mechanistic steps were proposed and found to follow, with expansion, the previously reported iminium-enamine route of typical class 1 aldolase enzymes. From the elementary steps, the first step which involves a bimolecular collision of acetone and proline was considered as the rate-determining step, having the highest activation energy of 59.07 kJ mol(−1). The mechanism was used to develop the rate law from which the overall rate constant was calculated and found to be [Formula: see text]. The new mechanistic insights and the explicit computation of the rate constant further improve the kinetic knowledge of the reaction.