The Behavior of 1, 4-Benzodiazepine Drugs in Acidic Media. XVI. Estimation of cis/trans Isomer Ratio of Benzodiazepinooxazoles Using Nuclear Magnetic Resonance Shift Reagent

Abstract

The ratio of cis/trans isomers (referring to 11b-substituent and 2- or 3-substituent) of benzodiazepinooxazoles was estimated by using the lanthanide shift reagent (Eu (fod)₃-d₂₇) for nuclear magnetic resonance (NMR) spectroscopy. The amide carbonyl oxygen at 6-position is considered to coordinate with the reagent, because the largest downfield shifts were observed at the amide carbonyl carbon (C-6) in ¹³C-NMR and the amide hydrogen (H-7) in ¹H-NMR. The ratios depend largely on the substituents at 11b-, 2-, and 3-positions. The cis isomer for compounds having 11b-hydrogen increases with an increase in the bulkiness of the substituents at 2-position. The cis isomer for compounds having 3-methyl group decreases with change from 11b-2'-chlorophenyl group (mexazolam) to 11b-hydrogen.