Enantiomeric and racemic oxazepam (OX), 3-0-methyloxazepam (MeOX), and 3-0-ethyloxazepam (EtOX) were used to study racemization, heteronucleophilic, and homonucleophilic substitution reactions in anhydrous acidic methanol and ethanol. Kinetics of racemization and nucleophilic substitution reactions in nondeuterated and deuterated solvents were determined by circular dichroism spectropolarimetry, chiral stationary phase high-performance liquid chromatography (HPLC), reversed-phase HPLC, and mass spectrometry. Several reactions occurred when @)-OX, for example, was dissolved in acidic methanol: (1) (S)-OX itself underwent spontaneous racemization, (2) the 3-hydroxyl group of @)-OX was stereoselectively substituted by the methoxy group of methanol to form MeOX enriched in (S)-MeOX, (3) the 3-methoxy group of (S)-MeOX was stereoselectively substituted by the methoxy group of methanol to form MeOX enriched in (3-MeOX, and (4) the 3-methoxy group of (R)-MeOX was stereoselectively substituted by the methoxy group of methanol to form MeOX enriched in (R)-MeOX. Repetitive reactions 3 and 4 eventually resulted in a racemic MeOX. Similar reactions occurred for an enantiomeric OX in acidic ethanol.