Abstract
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.
Original language | English |
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Journal | European Journal of Organic Chemistry |
DOIs | |
Publication status | Accepted/In press - 2024 |
Keywords
- amide planarity
- atropisomers
- benzodiazepines
- hammett constants
- rotational barrier