Ultrasound-assisted synthesis of benzazole-based imidate derivatives: a DFT investigation of the thermodynamic stability and electronic properties of the synthesized products.

A rapid, efficient, and simple ultrasonic-assisted protocol is reported herein for the synthesis of benzazoles bearing an imidate skeleton via the one-pot reaction of isocyanides, various alcohols, and benzo(thiazole-oxazole-imidazole) using Cs2CO3 as an active base, a THF solvent, and a copper catalyst, without the use of additional ligands under ultrasonic conditions for 50 minutes with good efficiency. The role of ultrasound in this reaction is to reduce the reaction time, increase the efficiency of product preparation, and simplify the work-up process. The use of simple and available raw materials, mild copper catalytic reaction conditions, easy purification with the help of solvents, and finally the synthesis of 12 new compounds from benzazoles with an imidate skeleton are the notable features of this protocol. Moreover, in this study, density functional theory (DFT) calculations were performed to investigate the thermodynamic stability and electronic properties of benzazole derivatives containing different heteroatoms (X = O, S, N-H, and N-CH3) in THF using the SMD solvation model. The calculated thermodynamic parameters reveal that all the investigated systems are enthalpically stabilized, while the negative entropy contributions partially offset this stabilization. Among the studied derivatives, the N-H system exhibits the most favorable Gibbs free energy, whereas the oxygen-containing derivative shows a larger entropic penalty. Frontier molecular orbital analysis indicates that heteroatom substitution significantly affects the electronic structure of the benzazole framework. The HOMO-LUMO energy gap decreases upon replacing the N-methyl group with the oxygen substituent, accompanied by an increase in electrophilicity and more negative chemical potential values. These results demonstrate that the nature of the heteroatom plays an important role in controlling the thermodynamic stability and electronic reactivity of benzazole derivatives in solution.