Resolution and stability of oxazepam enantiomers

Abstract

A solvent mixture containing dioxane, acetonitrile, and hexane was found to be suitable as a mobile phase to resolve oxazepam enantiomers by chiral stationary phase high performance liquid chromatography using covalent Pirkle columns. The resolved oxazepam enantiomers in this solvent mixture had a racemization half-life greater than 3 days at 23°C. When desiccated at 0°C as dried residue, OX enantiomers were stable for at least 50 days with less than 2% racemization. The conditions which stabilized OX enantiomers significantly facilitated the determination of racemization half-lives of OX enantiomers in a variety of aqueous and nonaqueous solvents and at different temperatures.

Investigation of the stereodynamics of molecules and catalyzed reactions by CE

“…Activation barriers and activation parameters were determined from temperature-dependent Table 2). These results suggested an acid or base catalyzed enantiomerization process via a keto-enol tautomerism [39] in contrast to a previously reported ring opening mechanism [77]. Recently, the enantiomerization barriers determined by DMEKC were confirmed by independent methods [78].…”

Racemization and stereoselective alcoholysis of temazepam

“…7,[12][13][14][15][16][17][18] Enantiomers of 3-hydroxy-1,4-benzodiazepines are stable in aprotic solvents and racemize with different rates in various protic solvents. 17,18 Lhoest and Frigerio 19 proposed a ring-chain tautomerism to account for the formation of 6-chloro-4-phenylquinazoline-2-carboxyaldehyde by thermolytic rearrangement of OX during gas chromatographic analysis. The lability of the C3-N4 bond of OX was also implied by the formation of 6-chloro-4-phenylquinazoline-2-carboxyaldehyde from OX following heating at 200°C for 5 min.…”

Acid‐catalyzed stereoselective heteronucleophilic substitution and racemization of 3‐O‐methyloxazepam and 3‐O‐ethyloxazepam

“…It appeared that the rate constant was insensitive to the dielectric constant of the solvent when the reaction proceeded at or near the maximum rate [k = k,' in Eqs. (6) and (7) in the Introduction section]. Taken together, the results indicated that the acid-catalyzed heteronucleophilic substitution of EtOX in MeOH was also a reaction between a positively charged molecule and a neutral molecule.…”