Quantum Chemistry Studies On The Mechanism Of Baylis-Hillman Reaction

B3LYP method of density functional theory (DFT) was employed to study the mechanism of trimethylamine-catalyzed Baylis-Hillman reaction between acraldehyde and formaldehyde, both in gas and in methanol solvent. The solvent effect of methanol on the reaction process was investigated with the CPCM method of polarizable continuum model and the supermolecular handling, respectively.The optimized structures and energies of the reactants, intermediates, transition states and products of two reaction channels (corresponding to syn-acraldehyde and anti-acraldehyde) in gas or in methanol solvent were obtained. The potential energy profiles reveal the processes of the trimethylamine-catalyzed Baylis-Hillman reaction between acraldehyde and formaldehyde in gas or in methanol solvent at the microscope level.In gas, the reaction only involves the carbon-carbon bond formation process and the intramolecular proton-transfer process, and the former is the rate-determining step. The reaction process in methanol solvent can be deduced from the computational results with CPCM solvent model and the supermolecular handling, namely the reaction involves four steps in the methanol solvent. The nucleophilic addition of trimethylamine to acraldehyde generates an enolate. Nucleophilic attack of the enolate on the aldehyde forms the carbon-carbon bond, followed by the proton-transfer process and the further elimination generating the product and liberating the trimethylamine catalyst. Methanol molecule participates in the proton transfer process, which takes place by a intermolecular six-membered proton-transfer transition state structure instead of the intramolecular four- membered. Consequently, the activation energy of the proton-transfer process is reduced greatly,resulting in the carbon-carbon bond formation process become the rate-determining step. The results are consistent with Aggarwal's the latest dynamics experiments.