Deep eutectic solvent assisted synthesis of dihydropyrimidinones/thiones via Biginelli reaction: theoretical investigations on their electronic and global reactivity descriptors

Abstract

Deep eutectic solvents formed from hydrated metal chlorides and hydrogen bond donors (Type 4) were prepared and their catalytic activity was compared for the synthesis of dihydropyrimidinones/thiones via Biginelli reaction at room temperature. The one-pot multicomponent reaction was performed between ethyl acetoacetate, various aldehydes and urea/thiourea using DESs. Among the five DESs, excellent conversion was observed using DES 2 (ZrOCl₂·8H₂O with ethylene glycol at 1 : 2 ratio). The higher activity of DES 2 might be due to the strong hydrogen bonding ability and low viscosity of DES 2, which favoured the reaction as a catalyst. Further, the catalyst was recycled and reused up to four consecutive cycles without significant loss in its activity. The efficiency of the present catalyst was compared with some previous reports. Various structural and quantum chemical parameters (like energy gap), dipole moment, ionization potential, electron affinity, chemical potential (μ), global hardness (η), softness (μ), electronegativity (χ), electrophilicity index (ω) of the pharmaceutically important Biginelli products were investigated using B3LYP functional at 6-31G* level, as implemented in Gaussian 09.