One‐Pot Multicomponent Regioselective Synthesis of Novel 2‐(Phenylamino)‐5‐(Trifluoromethyl)‐5,6‐Dihydro‐4 <i>H</i> ‐1,3,4‐Thiadiazin‐5‐ol Derivatives and Insight Mechanism Through DFT Studies

Abstract Herein, we report one‐pot, multicomponent regioselective synthesis of novel 2‐(phenylamino)‐5‐(trifluoromethyl)‐5,6‐dihydro‐4 H ‐1,3,4‐thiadiazin‐5‐ol derivatives under the mild basic reaction condition. The reaction of aromatic hydrazines with various substituted phenyl isothiocyanate and 3‐bromo‐1,1,1‐trifluoroacetone in DMF ( N,N ‐dimethylformamide) with catalytic amount of DABCO (1,4‐diazabicyclo[2.2.2]octane) affords 2‐(phenylamino)‐5‐(trifluoromethyl)‐5,6‐dihydro‐4 H ‐1,3,4‐thiadiazin‐5‐ols. Further, the novel synthesized compounds were characterized by FT‐IR, 1 H/ 13 C NMR spectroscopy, and LC–MS spectroscopic techniques. To understand the deeper insight into the regioselectivity and structural preference of the synthesized product, density functional theory (DFT) calculations were performed. DFT studies supported the experimental observations toward the formation of 6‐membered thiadiazin‐5‐ol regioisomer in major over the 5‐membered thiazolidinol heterocycle. Ultimately, the easy handling of all substrates and catalyst, mild reaction condition, short reaction time, simple work‐up procedure, and moderate‐to‐excellent product yield are some of the notable advantages of this development.