Modeling and synthesis of bifunctional dual activation thiourea organocatalysts for Michael addition of pyrazole

Modeling of Michael addition of pyrazole to cinnamaldehyde in the presence of six thiourea catalysts has been done at the DFT (B3LYP/6-31+G(d,p)) level. Four catalysts incorporating 2-pyridyl moiety are found to exhibit bifunctional dual activation by encapsulating pyrazole molecule in the cavity of cinnamaldehyde-catalyst complex thereby mimicking biosystem to bring the two reactants closer and also narrowing down the HOMO-LUMO gap. Guided by the theoretical results, four new N-bis(3,5-trifluoromethyl)phenyl-N’-2-pyridylthiourea catalysts were synthesized and well characterized on the basis of IR, 1 H and 13 C NMR and HRMS studies. X-ray crystal structure of one catalyst could also be done. On determining comparative catalytic efficacies of these catalysts experimentally for the model reaction of pyrazole with cinnamaldehyde, the catalyst N-bis(3,5-trifluoromethyl)phenyl-N’-2-(5-chloropyridyl)thiourea was found to be most effective, which is in accordance with the theoretical modeling results.