Atropisomeric Properties of 5N-Benzoyl-1,5-benzodiazepin-2-ones: Substituent Effects on Rotation around the Ar−N(CO) Axis

5N-Benzoyl-1,5-benzodiazepin-2-ones with various substituents were synthesized and their atropisomeric properties were analyzed. For the rotational isomers (E/Z) based on the amide bond [N−C(=O)], the E-isomers were preferentially formed regardless of the substituents. Atropisomers (aR/aS) due to the Ar−N(CO) (sp²-sp²) axis were isolated using chiral HPLC, and the rotational barrier (ΔG^≠) in thermal isomerization was measured. The rotation barrier about the Ar−N(CO) axis was affected by both the substituents at the C6-position and the p-substituents on the benzoyl group. The substituents at C6 (R¹) caused both steric and electronic effects. On the other hand, the p-substituents (R²) on the benzoyl group caused electronic effects: the electron-donating group (EDG) lowered the ΔG^≠ value, whereas the electron-withdrawing group (EWG) raised it. The ΔG^≠ values were linearly correlated with the magnitude of the electronic effect (Hammett σ constants) of functional groups (R²). The EDG causes an increase in the electron density on the carbonyl moiety in the amide, which may disturb the planarity of the amide bond, resulting in a decrease in the ΔG^≠ value.