Regioselective N‐Acylation of Thiazol‐4(5H)‐ones Enabled by AlCl ₃ : Experimental, Docking and DFT Investigations

An efficient and selective AlCl 3 ‐mediated protocol for the N‐acylation of 2‐(phenylamino)thiazol‐4(5H)‐ones has been developed. The reaction proceeds smoothly under mild conditions, affording N‐(4‐oxo‐4,5‐dihydrothiazol‐2‐yl)‐N‐phenylpropionamide derivatives in excellent yields. In comparison with Brønsted acids and other Lewis acids, AlCl 3 exhibits superior control over monoacylation, effectively suppressing competing diacylation pathways. The observed regioselectivity is rationalized using density functional theory (DFT) calculations. Molecular docking studies were employed to examine possible binding modes and non–covalent interactions, providing complementary structure–interaction insights without implying biological activity.