Investigation of Vilsmeier–Haack Formylation Reactions on Substituted 4-Aryl-2-Aminothiazole Derivatives

In this study, the Vilsmeier–Haack formylation reactions involving 4-phenyl-N-2-aminothiazole derivatives including urea, thiourea, methyl, and acetamide in the presence of POCl₃-DMF were systematically examined. The formylation reactions showed structural selectivity, such that either the thiazole ring, phenyl group, or amino group was formylated or instead compounds with N,N-dimethylformimidamide groups were formed by combining with the free amino group present in the reaction medium. The single crystals of the molecules (7) N-benzyl-4-phenylthiazol-2-amine and (17) N-(5-methyl-4-phenylthiazol-2-yl)acetamide were successfully obtained, and their structures were elucidated via X-ray crystallography. All the compounds were synthesized and characterized using FT-IR, ¹H-NMR, and ¹³C-NMR techniques. The crystal structure of compound (17) exhibits an O,S-syn conformation. Moreover, density functional theory (DFT) calculations for compounds (7 and 17) were conducted. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels along with the molecular electrostatic potential (MEP) surfaces were ascertained. Quantum chemical parameters obtained from the ∆E value of compounds (7 and 17) were used to evaluate the reactivity, stability, and electronic behavior of molecules.