双相（O/W）识别手性萃取芳香酸对映体的动力学研究

【作者】 李洪建；

【导师】 唐有根； 唐课文；

【作者基本信息】 中南大学 ， 有机化学， 2011， 硕士

【摘要】 本文采用一种新的手性萃取分离技术——双相识别手性萃取法对苯基琥珀酸、a-环己基扁桃酸和萘普生三种外消旋手性化合物进行萃取拆分的动力学研究。实验是在优化的萃取体系下进行的,以便为药物对映体的萃取分离提供理论依据和技术参数。主要内容和结果如下：(1).采用双相(O／W)识别手性萃取体系对苯基琥珀酸对映体进行动力学拆分,通过恒界面池法研究了反应萃取的动力学特性；以具有工业应用前景的亲水性羟丙基-B-环糊精以及疏水性的酒石酸衍生物作为手性萃取剂,以传质速率为基准考察搅拌速度、水相pH、水相中萃取剂浓度、有机相中萃取剂浓度、对映体浓度以及两相接触面积等因素对苯基琥珀酸对映体萃取速率的影响。实验结果表明：双相(O／W)识别手性萃取苯基琥珀酸对映体的反应,其Has和HaR分别为5.9、4.2,属于“快反应”；而搅拌速度、水相pH、水相中萃取剂浓度、有机相中萃取剂浓度、对映体浓度对手性分离能力有显著的影响；反应是对映体浓度的一级反应,是萃取剂浓度的二级反应;R-PSA和S-PSA的反应速率常数分别为1.6×10-4m6/(mol2·s)和3.3×10-4 m6/(mol2·s)。(2).采用双相(O／W)识别手性萃取体系对a-环己基扁桃酸对映体进行动力学拆分,通过恒界面池法研究了双向识别体系对a-环己基扁桃酸对映体反应萃取的动力学特性；水相中使用亲水性的羟丙基-β-环糊精作为手性萃取剂,有机相中使用酒石酸衍生物作为手性选择体,以传质速率为基准考察搅拌速度、水相pH、水相中萃取剂浓度、有机相中萃取剂浓度、对映体浓度以及两相接触面积等因素对a-环己基扁桃酸对映体萃取速率的影响。实验结果表明：双相(O／W)识别手性萃取a-环己基扁桃酸对映体的反应,其Has和HaR分别为6.98、7.14,属于“快反应”；而搅拌速度、水相pH、水相中萃取剂浓度、有机相中萃取剂浓度、对映体浓度对手性分离能力有显著的影响；反应是对映体浓度的一级反应,是萃取剂浓度的二级反应；S-a-CHMA和R-a-CHNA.的反应速率常数分别为6.54x10-4mol-2 m6 s-1和6.84×10-4mol-2 m6 s-1。(3).采用双相(O／W)识别手性萃取体系对萘普生对映体进行动力学拆分,通过恒界面池法研究了双向识别体系对萘普生对映体反应萃取的动力学特性；水相中使用亲水性的羟丙基-β-环糊精作为手性萃取剂,有机相中使用酒石酸衍生物作为手性选择体,以传质速率为基准考察搅拌速度、水相pH、水相中萃取剂浓度、有机相中萃取剂浓度、对映体浓度以及两相接触面积等因素对萘普生对映体萃取速率的影响。实验结果表明：双相(O／W)识别手性萃取萘普生对映体的反应,其HaR和Has分别为13.27、9.33,属于“快反应”；而搅拌速度、水相pH、水相中萃取剂浓度、有机相中萃取剂浓度、对映体浓度对手性分离能力有显著的影响；反应是对映体浓度的一级反应,是萃取剂浓度的二级反应；S-NAP和R-NAP.的反应速率常数分别为1.26x10-4mol-2 m6s-1和2.52×10-4mol-2m6s-1。更多还原

【Abstract】 In this paper, a new chiral extract separation technique-biphasic (O/W) recognition chiral extraction was applied to investigate the kinetic mechanism of benzylsuccinic acid enantiomers, a- Cyclohexyl mandelic acid enantiomers and naproxen enantiomers. The experiments were carried out under the optimized system to provide theoretical bases and technique parameters for enantioseparation process. The main contents and results can be summarized as follows:(1). The kinetics of biphasic (O/W) recognition chiral extraction of benzylsuccinic acid enantiomers was investigated to determine the extraction mechanism. Study on the reactive extraction kinetics of phenylsuccinic acid enantiomers using a modified Lewise cell, with hydrophobic tartaric acid derivative in organic phase and hydrophilic hydroxypropyl-?-cyclodextrin (HP-?-CD) in aqueous phase as chiral selector; the mass transfer rate was chosed as the benchmark. The effects of agitation speed, interfacial area, initial enantiomers concentration in aqueous phase, initial extractants concentration of HP-?-CD and L-IBTA, pH of aqueous phase on initial extraction rate were separately researched.The experiment results demonstrate that, the kinetics of the extract reaction is fast with the values of Has and HaR were 5.9 and 4.2 respectively; and the effects of agitation speed, interfacial area, initial enantiomers concentration in aqueous phase, initial extractants concentration of HP-?-CD and L-IBTA, pH of aqueous phase on the chiral separation ability was significant. The reactions are found to be first order with respect to PSA enantiomers and second order with respect to Chiral extractants with the forward rate constants of 1.6×10-4 m6/(mol2·s) for R-PSA and 3.3x10-4 m6/(mol2·s) for S-PSA.(2). The kinetics of biphasic (O/W) recognition chiral extraction of a- Cyclohexyl mandelic acid enantiomers was investigated to determine the extraction mechanism. Study on the reactive extraction kinetics of a-Cyclohexyl mandelic acid enantiomers using a modified Lewise cell, with hydrophobic tartaric acid derivative in organic phase and hydrophilic hydroxypropyl-?-cyclodextrin (HP-?-CD) in aqueous phase as chiral selector; the mass transfer rate was chosed as the benchmark. The effects of agitation speed, interfacial area, initial enantiomers concentration in aqueous phase, initial extractants concentration of HP-?-CD and D-IBTA, pH of aqueous phase on initial extraction rate were separately researched.The experiment results demonstrate that, the kinetics of the extract reaction is fast with the values of Has and HaR were 6.98 and 7.14 respectively; and the effects of agitation speed, interfacial area, initial enantiomers concentration in aqueous phase, initial extractants concentration of HP-?-CD and D-IBTA, pH of aqueous phase on the chiral separation ability was significant. The reactions are found to be first order with respect to a-CHMA enantiomers and second order with respect to Chiral extractants with the forward rate constants of 6.54×10-4 m6/(mol2·s) for S-a-CHMA and 6.84×10-4 m6/(mol2·s) for R-a-CHMA.(3). The kinetics of biphasic (O/W) recognition chiral extraction of Naproxen enantiomers was investigated to determine the extraction mechanism. Study on the reactive extraction kinetics of Naproxen enantiomers using a modified Lewise cell, with hydrophobic tartaric acid derivative in organic phase and hydrophilic hydroxypropyl-?-cyclodextrin (HP-B-CD) in aqueous phase as chiral selector; the mass transfer rate was chosed as the benchmark. The effects of agitation speed, interfacial area, initial enantiomers concentration in aqueous phase, initial extractants concentration of HP-?-CD and L-IBTA, pH of aqueous phase on initial extraction rate were separately researched.The experiment results demonstrate that, the kinetics of the extract reaction is fast with the values of HaR and HaS were 13.27 and 9.33 respectively; and the effects of agitation speed, interfacial area, initial enantiomers concentration in aqueous phase, initial extractants concentration of HP-?-CD and L-IBTA, pH of aqueous phase on the chiral separation ability was significant. The reactions are found to be first order with respect to PSA enantiomers and second order with respect to Chiral extractants with the forward rate constants of 1.26×10-4 m6/(mol2·s) for S-NAP and 2.52×10-4m6/(mol2·s) for S-NAP和R-NAP.更多还原