Kinetic Study for Biphasic Recognition Chiral Extraction of Naproxen Enantiomers with Hydrophobic L-iso-butyl Tartrate and Hydrophilic Hydroxypropyl-β-Cyclodextrin

The kinetics of biphasic recognition chiral extraction of naproxen (HA) enantiomers was investigated to determine the extraction mechanism, with hydrophobic L-iso-butyl tartrate (L-IBTA) in the organic phase and hydrophilic hydroxypropyl-β-cyclodextrin (HP--CD) in the aqueous phase. The two-phase homogeneous reaction model was selected over the interfacial reaction model, because there is a clear physical solubility of naproxen enantiomers in both the aqueous phase and the organic phase. The reactions between the HA enantiomers and L-iso-butyl tartrate in a stirred cell fall in Regime 3; the extraction is accompanied by two fast chemical reactions in the diffusion film. The reactions have been found to be first order with respect to HA enantiomers and second order with respect to L-IBTA. The forward rate constants for S-HA and R-HA are 1.26?×?10^?4 mol^?2 m⁶ s^?1 and 2.52?×?10^?4 mol^?2 m⁶ s^?1, respectively. With the increase of HP--CD concentration in the aqueous phase, high enantioselectivity was obtained, but the extraction rates decreased. These data will be useful in the design of extraction processes.     

羟丙基-β-环糊精萃取苯基琥珀酸的动力学特性

为研究β-环糊精衍生物类萃取剂萃取芳香酸对映体的动力学行为,以苯基琥珀酸对映体（PSA）为分离溶质,羟丙基-β-环糊精（HP-β-CD）为萃取剂,采用恒界面池法考察了搅拌速率、两相接触面积、萃取剂和溶质浓度等操作参数对苯基琥珀酸对映体萃取动力学的影响。实验结果表明：HP-β-CD萃取PSA为准一级反应萃取过程;且萃取发生在相界面,萃取速率随PSA的初始浓度的增大而增大,且呈线性关系。     

Selective Enantioseparation of Racemic Amlodipine by Biphasic Recognition Chiral Separation System

The biphasic recognition chiral extraction process was developed and applied to separate amlodipine enantiomer. The chiral extraction system contained tartaric acid derivatives in the organic phase and β-cyclodextrin derivatives in the aqueous phase. The effect of extraction equilibrium time and the influence of different types of tartaric acids, types of β-cyclodextrin derivatives, organic solvents, and buffer pH were investigated. The results indicated that hydroxypropyl-β-cyclodextrin (HP-β-CD) showed a higher recognition ability toward (S)-amlodipine than (R)-amlodipine while dibenzoyl-D-tartrate demonstrated the strongest ability among tartaric acid derivatives to bind with (R)-amlodipine. The distribution ratios for (S)-amlodipine (k_S) and (R)-amlodipine (k_R) gave optimum values at pH 5.0 of 16.54 and 0.78, respectively. Biphasic chiral recognition extraction has great significance for preparative separation of (S)-amlodipine. It can also be used to design and apply the enantioseparation process.     

Experimental and Simulation on Enantioselective Extraction in Centrifugal Contactor Separators

The increasing demand for optically pure compounds stimulates the development of new chiral separation processes on an industrial scale. The enantioselective liquid–liquid extraction (ELLE) of phenylsuccinic acid (PSA) enantiomers using hydrophilic hydroxyphenyl‐β‐CD as extractant (C) was studied experimentally in a countercurrent cascade of 10 centrifugal contactor separators at 293 K. Based on a single‐stage equilibrium model and the law of conservation of mass, a multistage equilibrium model of ELLE was developed to investigate the influence of changes in the process parameterssuch as phase ratios and concentrations on extraction efficiency. The multistage equilibrium model was verified experimentally with a good agreement. The model was applied to predict the symmetrical separation of PSA enantiomers. By modeling, optimal process parameters for the symmetrical separation of PSA enantiomers can beachieved. The minimum number of stages was determined at 22 and 24 for ee_eq>98% and ee_eq>99%, respectively. © 2013 American Institute of Chemical Engineers AIChE J, 59: 2594–2602, 2013     

手性表面活性剂在手性合成、识别及拆分中的应用

当今社会对单一对映体的需求越来越大,由于手性表面活性剂具有区域选择性、手性催化能力及手性识别能力,因而在手性合成、手性识别及手性拆分中的应用也越来越受封重视。文章综述了近年来手性表面活性剂在不对称催化、乎性识剐及手性拆分中的应用。     

手性化合物的萃取拆分研究

分析了目前外消旋体拆分方法 ,对萃取拆分法作了分析总结。至少存在三种萃取拆分体系 ,即 :亲和萃取拆分体系 ,配位萃取拆分体系和形成非对映体立体异构体萃取拆分体系。膜技术用于萃取拆分过程有助于实现萃取拆分分离。萃取拆分技术适用性强、便于连续拆分有望成为外消旋体拆分分离操作的先进技术。     

乙草胺对映体的手性识别

乙草胺对映异构体在纤维素衍生物手性固定相上得到了分离,分离系统为高效液相色谱,流动相为正己烷和石油醚,流动相中添加了乙醇、内醇、异丙醇和丁醇为极性改性剂,考察了各种改性剂及其含量对拆分的影响。在0℃～25℃范围内研究了温度对拆分的影响。试验结果显示,丙醇和丁醇在2％～15％含量范围内对乙草胺没有分离效果,乙醇和异丙醇有一定的分离效果。流动相中醇含量的减少及温度的降低有利于对映体的拆分,在异丙醇含量为2％,温度为0℃时有最佳的分离效果,分离因子为1.20。     

反相手性液相色谱法在对映体拆分中的应用研究

手性分离是色谱分离的难点,且常见的手性分离多为正相色谱分离模式。然而,手性物质往往存在于含水体系中,手性化合物的拆分和检测在反相分离模式中具有更好的相容性。分别介绍了手性药物、手性氨基酸的反相色谱分析进展,并综述了手性添加剂在反相色谱手性分离中的应用,对手性分离和分析具有重要的参考意义。     

手性二氧大环多胺对苦杏仁酸的手性识别研究

以自合成的手性二氧大环多胺作为手性溶解剂,采用NMR技术对苦杏仁酸进行手性识别研究.当主客体混合后,主客体的质子峰在1HNMR图谱中均发生不同程度的化学位移,且苦杏仁酸的α-次甲基氢的化学位移变化值在主客体摩尔比为1:1时达到最大,从而表明主客体之间可能形成了较为稳定的摩尔比为1:1 的超分子复合物.这一研究结果表明手性二氧大环多胺与苦杏仁酸具有较强的超分子作用,可用于苦杏仁酸的手性识别及对映体拆分.     

双相（O/W）识别手性萃取分离多巴对映体研究

为了研究多巴在D（L）-2酒石酸异丁酯1,2二氯乙烷有机相和羟丙基-β-环糊精水相萃取体系中的分配行为;运用双相（O/W）识别手性萃取,考察酒石酸构型和浓度、羟丙基-β-环糊精浓度、水相pH值等因素对萃取性能的影响。羟丙基-β-环糊精对S-多巴对映体的识别能力大于对R-多巴对映体的识别能力,而L-酒石酸异丁酯的识别能力刚好相反;在羟丙基-β-环糊精和L-酒石酸异丁酯萃取体系中,多巴外消旋体一次萃取分离后R和S对映体的分配系数（kR和kS）分别为8.92和5.34,分离因子α达1.67;同时pH值和萃取剂浓度对手性分离能力有显著的影响。双相（O/W）识别手性萃取具有较强的手性分离能力,它对外消旋体化合物的制备性分离有着十分重要的意义。     

酒石酸衍生物作为手性选择剂在对映体的HPLC拆分中的应用

综述了近年来酒石酸衍生物作为手性选择剂在对映体的高效液相色谱 (HPLC)拆分中的应用。主要包括两个方面 :酒石酸衍生物作为手性流动相添加剂 (CMP)和酒石酸衍生物被制备成手性固定相 (CSP)的研究状况。阐述了酒石酸衍生物手性拆分对映体的多种机理 ,并对酒石酸衍生物在对映体的 HPLC手性拆分中的应用前景做了展望。     

Enantioseparation of Ofloxacin Enantiomers by Mixed Extractants in Biphasic System

The distribution behavior of ofloxacin enantiomers was examined in a biphasic system containing β-cyclodextrin in aqueous phase and a complex formation of O'O-dibenzoyl-(2R,3R)-tartaric acid (L-DBTA) and di(2-ethylhexyl)phosphoric acid in organic phase as the mixed extractants. The influences of pH, initial concentration of ofloxacin, phase ratio, and concentration of extractants were studied. The experimental results showed that both the distribution ratio and enantioselectivities of ofloxacin enantiomers were greatly improved. A higher enantioseparation efficiency with a maximum separation factor of 2.48 and enantiomeric excess of 40.4% can be obtained under the optimal experimental conditions. It could be very helpful to achieve high effective enantioseparation using the mixed extractants, which would be the guidelines for industrial amplification of chiral extraction separation.     

手性表面与对映异构体的结晶分离

近年来,手性表面在分离对映异构体方面的重要性引起科学工作者的很大兴趣。手性表面对手性分子的识别和区分能力成为人们最感兴趣的领域之一。文章回顾了用手性自组装单分子层做分离助剂来结晶分离外消旋物的研究进展。     

环糊精及其衍生物在气相色谱手性分离中的应用

阐述了手性化合物分离的必要性，以及环糊精(CD)及其衍生物(CDs)的结构特点和作为气相色谱固定相的可能性，并简要概括CDs在气相色谱手性分离中的应用。     

用微晶纤维素三醋酸酯研制的手性色谱柱分离E-二苯乙烯环氧化物对映体

采用化学接枝的方法制备了微晶纤维素三醋酸酯和氨基硅胶,减压蒸发溶剂法将微晶纤维素三醋酸酯涂布到氨基硅胶上制备成手性固定相,最后在高压气动泵下进行湿法装柱自制成手性柱。柱子对E-二苯乙烯环氧化物的对映体进行拆分:结果表明适宜分离条件为流动相v(正己烷)∶v(乙醇)=99∶1、温度为10℃、流速为0.4 mL/min时。     

三烷基胺萃取丙酸的动力学特性

为研究胺类萃取剂萃取有机酸的动力学行为 ,以丙酸稀溶液为分离溶质 ,三烷基胺 ( 730 1)为萃取剂 ,正辛醇和煤油的混合物为稀释剂 ,采用恒界面池法考察了萃取剂和溶质浓度、搅拌速率、两相接触面积、温度等操作参数对丙酸萃取动力学的影响。结果表明 :730 1萃取丙酸为准一级反应萃取过程 ;且萃取发生在相界面 ,即界面反应萃取机制 ;表观活化能为 2 8.5kJ/mol,萃取速率受温度的影响不显著 ;经计算 ,在一般的萃取塔操作条件下 ,该体系的萃取过程为反应和传质过程的混合控制。     

Kinetic study on biphasic recognition chiral extraction for separation of α‐cyclohexyl‐mandelic acid enantiomers

BACKGROUND: Chiral solvent extraction is a potentially attractive chiral separation technique. It is essential to know the intrinsic complexation kinetics for selection, design and operation of reactive extraction equipment and for reliable scale‐up. The objective of this research is to study the kinetics of biphasic recognition chiral extraction of α‐cyclohexyl‐mandelic acid (α‐CHMA) enantiomers using a modified Lewis cell. RESULTS: The experimental results demonstrate that the extraction reaction kinetics is fast, and the reactions are first order with respect to α‐CHMA and second order with respect to D‐IBTA, with forward rate constants of 6.54 × 10^?4 mol^?2 m⁶ s^?1 for S‐α‐CHMA and 6.84 × 10^?4 mol^?2 m⁶ s^?1 for R‐α‐CHMA. With increase of HP‐β‐CD concentration in aqueous phase, enantioselectivity increases, while the overall mass transfer coefficients decrease. CONCLUSIONS: Sufficient enantioselectivity and fast kinetics of extraction can be obtained in the BRCE system at HP‐β‐CD concentration of 0.1 mol L^?1 and D‐IBTA concentration of 0.2 mol L^?1. These data will be useful in the design of extraction processes. Copyright © 2012 Society of Chemical Industry     

Copper Extraction Kinetics by Beta-Diketone Derivatives (Acylpyrazolones and Acylisoxazolones) in Water/Chloroform Biphasic System

Abstract

Copper(II) extraction and back-extraction rates were determined in a water/chloroform system using a bell-shaped transport cell. Various 1-phenyl-3-methyl-4-acyl-pyrazol-5-ones (with acyl = benzoyl, 2-thenoyl, octadecanoyl, p-tert-butylbenzoyl, 3-phenyl-propanoyl, and iso-nonanoyl) and 3-phenyl-4-acylisoxazol-5-ones (with acyl = benzoyl and p-tert-butylbenzoyl) were considered. The back-extraction rate is shown to be limited by the diffusion of the complex in the organic unstirred layer, whatever the stirring speed and whatever the ligand considered. At low stirring speed, the extraction rate appears to be limited by the diffusion of either a complex or a ligand species in the unstirred layers, depending on the pH. At high stirring speed, the extraction rate is limited by the interfacial complexation. The extraction rate dependence on side-group variation cannot be correlated with hydrophobicity or acidity of the extractants and may be explained by structural differences of the CO vicinal group of the acyl.     

Chiral Separation of Ketoprofen Enantiomers by Preparative and Simulated Moving Bed Chromatography

The pharmaceutical industry is now directed to the market of more safety and efficient drugs, based on single enantiomers. Ketoprofen, still used as a racemic pharmaceutical drug, belongs to the profens class, one of the most representative of the non-steroidal anti-inflammatory drugs. This work presents the chiral separation of ketoprofen enantiomers by simulated moving bed technology, using a laboratory scale unit (the FlexSMB-LSRE®) with six columns, packed with the Chiralpak AD® stationary phase (20 μm). A comparative study between a mobile phase composed of a traditional high hydrocarbon content (10%ethanol/90%n-hexane/0.01%TFA) and a strong polar organic composition (100%ethanol/0.01%TFA) is presented. The study includes the measurement of the adsorption isotherms, elution, and frontal chromatography experiments, carried out on a SMB column for both compositions. The results obtained allowed the prediction and optimization of the SMB operation. Using pure ethanol as solvent and a racemic feed concentration of 40 g/L, purities above 98.6% on both outlet streams were obtained, with a productivity of 3.84 g_feed/(L_bed.hr) and a solvent consumption of 0.78 L_solvent/g_feed. The results obtained in the experimental separation of ketoprofen enantiomers by SMB chromatography indicates that pure ethanol presents better performances than the classic high hydrocarbon content composition.     

氨基酸的提取与精制

综合介绍了氨基酸提取过程中常用的分离技术以及近期的发展动态。如沉淀法、离子交换法、膜分离法和萃取法。并提出了氨基酸提纯精制的关键环节—结晶过程中应该注意的问题。