Study on protolytic equilibria of lorazepam and oxazepam by UV and NMR spectroscopy.

Protolytic equilibria in homogeneous and heterogeneous systems of lorazepam and oxazepam, which are sparingly soluble ampholytes from the class of 1,4-benzodiazepines, were studied at 25 degrees C and ionic strength of 0.1 M. Acidity constants and equilibrium constants in a heterogeneous system were determined. On the basis of the analysis of the corresponding 13C- and 1H-NMR spectra, deprotonation site in the molecules of the investigated compounds was predicted. Finally, the correlation between chemical shifts in the 1H-NMR spectra and the acidity of the amide proton of 1,4-benzodiazepines was established.