Quazepam在鹼性溶液中轉換成2-Oxoquazepam   全文下載

Conversion of Quazepam to 2-Oxoquazepam in Alkaline Solution

Quazepam [7-chloro-1-（N-2,2,2-trifluoroethyl）-5-（2 -fluorophenyl）-1,3-dihydro-2H-1,4-benzodiazepin-2-thione, QZ]是在臨床上使用的一種抗焦慮劑。QZ在鹼性溶液中會轉換成11個以逆相高壓液相層析能檢測得到的產物。其中最多的是2-Oxoquazepam [7-chloro-1-（N-2,2,2-trifluoroethyl）-5-（2'-fluorophenyl）-1,3-dihydro-2H-1,4-benzodiazepin-2-one, OQZ]。鹼性溶液中的反應動力學經由逆相高壓液相層析法分析，及自紫外與可見光吸收圖譜與時間的依存關係研究指出，QZ轉換成OQZ的反應是先形成一中間體，再形成OQZ主產物。反應機制可能是因QZ的C2缺電子，致使氫氧離子在C2產生親核加成反應，故而形成OQZ及其他之次產物。"

Quazepam [7-chloro-1-(N-2,2,2-trifluoroethyl)-5-(2 -fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-thione, QZ], an anxiolytic drug in clinical use, was converted in an alkaline solution to form 11 detectable products. 2-Oxoquazepam [7-chloro-1-(N-2,2,2-trifluoroethyl)-5-(2'-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one, OQZ] was the most abundant product formed. Reaction kinetics in alkaline solutions were analyzed by reversed-phase high-performance liquid chromatography. Time-dependent ultraviolet-visible absorption spectral measurements indicated an initial formation of an intermediate, followed by the formation of OQZ as the most abundant product. The electron-deficient C2 carbon of QZ probably undergoes a nucleophilic addition reaction by a hydroxide ion, resulting in the formation of primarily OQZ and other minor products.