Atropisomeric Properties of N-Aryl 5H-dibenz[b,f]azepines
Ryota Takano, Koki Yamane, Masanobu Suzuki, Kayo Nakamura, Hidetsugu Tabata, Tetsuta Oshitari, Hideaki Natsugari, Hideyo TakahashiAbstract
The conformation of 5H-dibenz[b,f]azepine is known to be closely related to biological activity. N-aryl C4-substituted 5H-dibenz[b,f]azepine derivatives were synthesized and their atropisomeric properties were investigated. Each atropisomer was isolated by chiral HPLC. It was determined that introducing an electron-withdrawing substituent at the 4′-position in pendant-Ar increased the stability of axial chirality. The energy barriers for the interconversion between atropisomers were controlled by the electronic effects of the 4′-substituent of pendant-Ar. Conformational analysis based on computational chemistry suggested that increasing the degree of sp2 hybridization of the central nitrogen improves the stability of axial chirality. These insights are expected to be valuable for the further development of antidepressant drugs based on 5H-dibenz[b,f]azepine.