On substituent effect on the benzodiazepinone system

► The substituent effect, aromaticity, and electron density were analyzed for benzodiazepinones. ► Regardless the environment and the substituent, the N1H tautomer is much more stable than the other. ► Higher aromaticity is the main reason for much higher stability of the N1H tautomers. ► Substituent in the benzo ring modifies electron density of the diazepinone ring. ► Possibly, benzodiazepinone pharmaceutical activity can be controlled by proper substitution.