The Behavior of 1,4-Benzodiazepine Drugs in Acidic Media. IV. Proton and Carbon-13 Nuclear Magnetic Resonance Spectra of Diazepam and Fludiazepam in Acidic Aqueous Solution

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Chemical species of diazepam and fludiazepam in an acidic aqueous solution (0.5 N DCl) were studied by means of proton and carbon-13 nuclear magnetic resonance (^<13>C-NMR) spectroscopy. These compounds were present in the form of a protonated iminium structure immediately after preparation of the solution and subsequently underwent slow hydrolysis of the iminium moiety to give a ring-opened benzophenone structure. The structures produced were in equilibrium with the corresponding ring-closed iminium structures. Furthermore, the benzophenone structures were present as an equilibrium mixture of rotating isomers around an amide (cis and trans isomers). The proportion of the benzophenone structure of fludiazepam in the equilibrium solution was greater than that of diazepam. The ratio of rotating isomers of the benzophenone structure that arose from fludiazepam was almost identical to that from diazepam. Assignments of the characteristic proton and carbon-13 resonances of these species and of the aromatic carbon-13 resonances of the iminium structure were carried out.
公益社団法人日本薬学会の論文
1985-12-25