Acid-base equilibria of 1,4-benzodiazepine 4-oxides by spectrophotometry.
Chlordiazepoxide (a 1,4-benzodiazepine 4-oxide) is an anxiolytic/hypnotic drug in clinical use. It was reported to be predominantly protonated at the N-oxide oxygen in acidic aqueous solutions at pH << 4.6 (pKa). We have studied the acid-base equilibria of three 1,4-benzodiazepine 4-oxides (chlordiazepoxide, diazepam 4-oxide, and nordiazepam 4-oxide) by ultraviolet-visible spectrophotometry. The results indicate that chlordiazepoxide is not protonated at the N-oxide oxygen, but rather at the nitrogen of an imine bond between C2 carbon and its nitrogen substituent in acidic media.
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002707:Chlordiazepoxide / Q000737:chemistry*; D003975:Diazepam / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D007700:Kinetics; D003708:Nordazepam / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
D007202:Indicators and Reagents; D003708:Nordazepam; D002707:Chlordiazepoxide; D003975:Diazepam