Highly Efficient Multicomponent One‐Pot Synthesis of Benzoxazin‐2‐one Using Yb‐triflate and Their Potential as AChE Inhibitor

AbstractIn this research we report a synthetic protocol for one‐pot synthesis of a cyclic carbamate‐ Benzo[e][1,3]oxazin‐2‐one by using Yb‐triflate as a catalyst from electron‐rich phenols, aliphatic aldehydes, and primary amines by incorporating CO from carbonyl diimidazole. The utilization of Yb‐triflate over other catalysts like Zn‐triflate, Cu‐triflate, Sm‐triflate, Fe‐triflate, BF3‐etherate, and TFA exhibits a 50%–75% yield of Benzo[e][1,3]oxazin‐2‐one. A total of 12 examples were synthesized. The cyclic carbamates were then checked for their potential as acetylcholine esterase (AChE enzyme) inhibitors using AutoDock Vina software. The molecular dynamics simulation study using GROMACS 2021.2 was also conducted to check the binding mechanism of the most active compounds, 4f and 4j (based on docking scores between −9.6 and −10.5 kcal/mol respectively) with the AChE enzyme (PDB ID 4EY6). The structures of the target compounds (4a–4l) were validated using IR, 1H, and 13C NMR spectroscopy, mass spectrometry, and elemental analysis demonstrating the effectiveness and practicality of the method developed.