Water‐Promoted Synthesis of Functionalized 5‐Amino‐2‐Oxo‐1,3‐Oxazepine‐6‐Carbonitriles: An Unexpected Divergence From Arylidenemalononitriles

A novel and unexpected synthesis of 5‐amino‐2‐oxo‐7‐aryl‐2,3‐dihydro‐1,3‐oxazepine‐6‐carbonitriles was achieved through the reaction of arylidenemalononitriles in water‐containing DMF. Originally aiming to synthesize benzoimidazo‐pyranopyridines, we observed a chemo‐selective cyclization where water acts as a nucleophile rather than a simple impurity. Under optimized conditions (DMF/Et 3 N at 80°C), a series of functionalized 5‐amino‐2‐oxo‐7‐aryl‐2,3‐dihydro‐1,3‐oxazepine‐6‐carbonitriles were obtained in high yields (80%–92%), while the starting material 4 was recovered unchanged. The structural identity and the existence of an imine‐enamine tautomeric equilibrium were rigorously established using FT‐IR, multinuclear NMR ( 1 H and 13 C), and D 2 O exchange experiments. A plausible mechanism involving an aziridine intermediate and the elimination of HCN is proposed to account for this transformation.