Formation of α,β-Unsaturated Imines in Apolar Aprotic Solvent: Effect of Hidden Acid Catalysts Analyzed by Theoretical Calculations

A theoretical investigation of the 1,2-additon and 1,4-addition reactions of benzylamine to crotonaldehyde in toluene solution is reported in this study, including the effect of trace amounts of acetic acid (AcOH) and methanesulfonic acid (CH₃SO₂OH). We have determined the reaction free energy profile and performed a detailed microkinetic analysis. Our results point out that this reaction system needs catalysis to take place and it was found that CH₃SO₂OH is a powerful catalyst, outperforming AcOH in lowering the free energy barrier for the 1,2-addition reaction, which leads to the formation of α,β-unsaturated imine. On the other hand, the 1,4-addition reaction has the direct nucleophilic attack of benzylamine to the β-carbon of s-cis conformation of crotonaldehyde as the rate-determining step, corresponding to slow kinetics. Our results suggest that the experimentally observed formation of the imine can be explained by the presence of hidden acid catalysts present in the reaction medium.

Keywords:
conjugated 1,4-addition; selectivity; Bronsted acid catalysis; reproducibility; microkinetic modeling