Hydrolysis of 2-Oxoquazepam in Alkaline Solution

□ 2-Oxoquazepam [7-chloro-1 -(AA2,2,2-trif luoroethyl)-5-(2’- fluorophenyl)-1,3-dihydro-2W-1,4-benzodiazepin-2-one, OQZ], a major pharmacologically active metabolite of quazepam, was hydrolyzed in NaOH solution to form a sodium salt of 2-(/V-2,2,2-trifluoroethyl)amino- 5-chloro-a-(2’-fluorophenylben...

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Veröffentlicht in:Journal of pharmaceutical sciences 1994-01, Vol.83 (1), p.58-63
Hauptverfasser: Yang, Shen K., Yang, Michael S.
Format: Artikel
Sprache:eng
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Zusammenfassung:□ 2-Oxoquazepam [7-chloro-1 -(AA2,2,2-trif luoroethyl)-5-(2’- fluorophenyl)-1,3-dihydro-2W-1,4-benzodiazepin-2-one, OQZ], a major pharmacologically active metabolite of quazepam, was hydrolyzed in NaOH solution to form a sodium salt of 2-(/V-2,2,2-trifluoroethyl)amino- 5-chloro-a-(2’-fluorophenylbenzylidene)glycine. The hydrolysis product was formed via a rapidly established acid-base equilibrium, followed by a rate-determining, ring-opening reaction involving two negatively charged ions. Following neutralization, the hydrolysis product was isolated by reversed-phase HPLC and subsequently identified by its UV-vis absorption and MS analyses. Kinetics of the hydrolysis reaction in acetonitrile/water mixture was studied by reversed-phase HPLC analysis as a function of water content, NaOH concentration, temperature, and ionic strength. In acetonitrile:0.05 N NaOH (1:1, v/v), the hydrolysis of OQZ had an energy of activation of 14.4 kcal/ mol and at 25 °C {AH* = 13.8 kcal/mol, AS* = -31.2 cal/K/mol, and AG* = 23.1 kcal/mol).
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.2600830114