Study on extraction kinetics of α-cyclopentylmandelic acid enantiomers with hydroxyethyl-β-cyclodextrin as chiral selector

In this work,the kinetic study on reactive extraction ofα-cyclopentylmandelic acid(α-CPMA)enantiomers was performed in a Lewis cell using hydroxyethyl-β-cyclodextrin(HE-β-CD)as chiral selector.The enantioselective complexation equilibrium between HE-β-CD andα-CPMA enantiomers was studied by phase solubility method.The important process parameters affecting the initial extraction rate were separately studied and the reaction rate equations were deduced.The optimal conditions for kinetic study were as follows:stirring speed of 75 r·min~(-1),interfacial area of 12.56 cm~2,pH of 2.5,initial HE-β-CD concentration of 0.05 mol·L~(-1),initialα-CPMA concentration of 5 mmol·L~(-1),and temperature of 278 K.The reaction has been found to be first order inα-CPMA and second order in HE-β-CD with the forward rate constants of 2.056×10~(-3)m~6·mol~(-2)·s~(-1)and 1.459×10~(-3)m~6·mol~(-2)·s~(-1)for(S)-α-CPMA and(R)-α-CPMA,respectively.The complexation equilibrium constants were evaluated as 61 L·mol~(-1) and 117 L·mol~(-1)for(S)-α-CPMA and(R)-α-CPMA,and the intrinsic enantioselectivity is estimated as 1.92.     

固定β-环糊精制备不溶性β-环糊精聚合物及其催化性能(英文)

Insoluble β-cyclodextrin polymers were prepared from β-cyclodextrin(β-CD) using epichlorohydrin(EPI) as crosslinking agent under basic conditions.The polymers were characterized by Fourier Transform Infrared(FTIR),Thermogravimetry(TG),X-ray diffraction(XRD) and TG-FTIR.The results demonstrated that the polym-erization between EPI and β-CD indeed occurred,and a number of CD rings were interconnected to form a three-dimensional network.Moreover,different factors influencing the polymerization,e.g.molar ratio of EPI to β-CD,the concentration of NaOH and reaction temperature,have been investigated.The polymer prepared under the optimal conditions(the molar ratio EPI:β-CD of 44,the NaOH concentration 50% in mass,and the temperature at 65 ℃) showed excellent thermal stability and insolubility in organic solvents or strong acid/base.In addition,the β-cyclodextrin polymers also presented high catalytic activity for aqueous oxidation of benzyl alcohol with hy-pochlorite as oxidant.     

Kinetics of Forward Extraction of Boric Acid from Salt Lake Brine by 2-Ethyl-1,3-hexanediol in Toluene Using Single Drop Technique

The kinetics of forward extraction of boric acid from salt lake brine by 2-ethyl-1,3-hexanediol in tolu-ene was investigated using the single drop technique. The factors affecting the extraction rate include interfacial area between aqueous phase and organic phase, initial concentration of boric acid in aqueous phase, initial concen-tration of 2-ethyl-1,3-hexanediol in organic phase, and extraction temperature. The experimental results show that the extraction rate increases with the increase of the initial concentration of boric acid and 2-ethyl-1,3-hexanediol, interfacial area of two phases, and temperature. With the temperature-dependence study, it is showed that the ex-traction is a diffusion-controlled process. The kinetic equation is presented for pH 1.0 in the aqueous phase and temperature of 318 K.     

具有羧酸官能团的功能性离子液体萃取分离钇的研究(英文)

A new kind of hydrophobic ionic liquids [1-alkyl-3-(1-carboxylpropyl)im][PF6] has been synthesized,and their extraction properties for Y(III) in the nitric acid medium was also investigated.The effects of extractant concentration,equilibrium pH of aqueous phase,salt concentration,temperature etc.were discussed.The results show that this kind of Task-Specific Ionic Liquid(TSIL) needs to be saponified before being used for the Y(III) ex-traction,and the extraction is acid dependent,and the extraction efficiency increases with the aqueous phase acidity decreasing.Furthermore,the loaded organic phase is easy to be stripped;more than 95% Y(III) could be stripped from the loaded organic phase when the stripping acidity is higher than 0.07 mol?L?1.The slope analysis technique is used to investigate the extraction mechanism,and a possible cation-exchange extraction mechanism is proposed in the present extraction system.     

Kinetic study on reactive extraction of phenylalanine enantiomers with BINAP-copper complexes

Enantioselective liquid–liquid extraction has attracted considerable attention for its potential use in large-scale production. Kinetic data are needed for the reliable scale-up of the process. This paper reports the kinetic study of reactive extraction of phenylalanine (Phe) enantiomers with BINAP–copper complex (BINAP–Cu) as a chiral selector. The theory of extraction accompanied by a chemical reaction was applied. The effects of agitation speed, interfacial area, pH value of aqueous phase, initial concentration of Phe enan-tiomers and initial concentration of BINAP–Cu on the specific rate of extraction were investigated. The for-ward rate constants of the reactions in the reactive extraction process are 7.93 × 10?5 m5/2·mol?1/2·s?1 for D-Phe and 1.29 × 10?4 m5/2·mol?1/2·s?1 for L-Phe.     

Equilibrium of liquid-liquid extraction of 2-phenylbutyric acid enantiomers: Experiment and model

The utilization of liquid–liquid extraction for the separation of 2-phenylbutyric acid(2-PBA) enantiomers was proposed. Factors affecting the extract process were investigated, including organic solvents, β-cyclodextrin derivatives, cyclodextrin concentration, p H and temperature. A model was proposed to describe the separation process based on the homogeneous phase reaction mechanism. Important parameters of this model were determined experimentally. The physical distribution coefficients for molecular and ionic 2-PBA were0.129 and 7.455, respectively. The equilibrium constants of the complexation reactions were 89.36 and36.78 L·mol~(-1) for(+)-and(-)-2-PBA, respectively. The model was verified by experiments and proved to be an excellent means to optimize the separation system. Through modeling prediction and experiment, the best conditions(e.g., pH value of 3.00, extractant concentration of 0.1 mol·L~(-1), temperature of 5.0 °C) were acquired. Under this condition, the maximum enantioselectivity(2.096) was obtained.     

用198Au示踪法研究季铵盐体系萃取金

The solvent extraction of KAu(CN)2 from alkaline solution by quaternary ammonium salts (trialkylmethylammonium chloride or cetyltrimethylammonium bromide) waw investigated by means of ^198Au radioactive tracer method. Various parameters,such as the gold (I) concentration in aqueous phase,the modiffer,emulsifiation at the interface of two phases, and phase ratio used in the extraction of gold (I) were studied. The results demonstrate that almost all gold (I) in the aqueous phase was practically extracted into the organic phase. The water content in the organic phase decreased significantly with increase of gold (I) concentration using long chain alcohol as modifier,in contrast with the system with tributyl phosphate (TBP) as modifier. Emulsification at the interface of two phases decreases with an increase of modifier concentration in the organic phase or with the addition of a small amount of lysozyme into the aqueous phase. The method with ^198Au tracer can be directly used to determine the Au(I) concentration both in aqueous and organic phases, which is especially suitable for the low concentration of Au(I).     

Direct extraction of Mo(Ⅵ) from sulfate solution by synergistic extractants in the rotation column

Direct extraction of molybdenum from sulfate solution with synergistic extractants(mixture of D_2EHPA and TBP)was studied in the rotation column. The influence of extractant concentration and initial pH of aqueous phase was studied in the bench scale experiments. The outcomes demonstrated that the synergistic solvent extraction enhances the constancy of the extracted complexes for transfer into the organic phase. In the continuous experiments, the effect of different operating parameters such as speed of agitation, inlet solvent flow rate and inlet aqueous flow rate on the holdup, mean drop size, drop size distribution, slip and characteristic velocities and extraction percentage were examined. Modified correlations were proposed for prediction of hydrodynamic parameters with consideration of reaction extraction condition in the rotation column. Furthermore, these correlations were compared with the experimental data. According to the results, the direct extraction of Mo(Ⅵ) from aqueous solution and sulfuric media with extraction efficiency of 90.4% was obtained at higher rotor speed(240 r·min~(–1) rpm) in this column.     

A novel constant interfacial area cell for determining the extraction kinetics of Er(Ⅲ) from chloride medium

A novel constant interfacial area cell(NCIAC),by spatially separating the agitation from liquid flow circulation of organic and aqueous two phases,was suggested to obtain detailed kinetic data for Er(Ⅲ) extraction from chloride medium by 2-ethyl-hexyl-phosphonic acid mono-(2-ethylhexyl) ester(EHEHPA).Different from the traditional Lewis cell and the constant interfacial area cell with laminar flow,the concentrations of Er(Ⅲ) in organic and aqueous two phases were uniform,and the stability of the interfacial area between the two phases could be controlled effectively.Therefore,the special requirements for the design of agitators in the traditional Lewis cell and the constant interfacial area cell for minimizing the influence of diffusion resistance could be avoided.Experimental results indicated that the extraction kinetics was mainly affected by the aqueous flow rate,interfacial area between organic and aqueous two phases,and the aqueous p H values.An extraction kinetic equation was suggested based on the experimental data.     

超临界流体色谱手性分离布洛芬

The separation method using chiral stationary phase （CSP） for the preparation of enantioselective compound was widely used. In this work, supercritical fluid chromatography（SFC） was proposed to resolve the chiral mixtures. To determine the optimum operating conditions for the chiral separation of the racemic ibuprofen, the retention factors and resolutions with the change in pressure, temperature and the content of IPA （%, by volume） in supercritical CO2 were investigated. Experiments showed that the retention factor decreased with the increase of pressure and decrease in temperature. The retention factor was also influenced by the content of IPA in mobile phase, as the content of IPA in the supercritical fluid increased, the retention factor decreased. The resolution of the enantiomers became worse with the increase of IPA in the supercritical fluid. Through optimizing the experimental conditions, a SFC procedure with 13MPa, 311.15K and 4% IPA in CO2 was obtained. The peak shape of the enantiomers was symmetric with supercritical fluid chromatography when compared to the asymmetric peak shape obtained by the conventional liquid chromatography. This work demonstrated that the developed supercritical fluid chromatography procedure was suitable for the chiral separation of ibuprofen enantiomers.     

Enantioselective separation of R,S-phenylsuccinic acid by biphasic recognition chiral extraction

A new process has been developed to separate phenylsuccinic acid (H₂A) enantiomers, based on the oppositely preferential recognition of hydrophobic and hydrophilic chiral selectors in organic and aqueous phases, respectively, which is named as biphasic recognition chiral extraction (BRCE). BRCE system is established by adding hydrophobic l-iso-butyl tartrate in organic phase and hydrophilic β-cyclodextrin (β-CD) derivative in aqueous phase, which preferentially recognize S-H₂A and R-H₂A, respectively. The studies performed involve two enantioselective extractions in a biphasic system, where H₂A enantiomers form four complexes with β-CD derivative in aqueous phase and l-iso-butyl tartrate in organic phase, respectively. Here it is shown that the efficiency of the extraction depends, often strongly, on a number of process variables, including the types of organic solvents and β-CD derivatives, iso-butyl tartrate configurations, the concentrations of the extractants and H₂A enantiomers, pH and temperature. Phase-equilibria in BRCE systems is governed by the complex chemical equilibria in both the organic and aqueous phases. By changing the monophasic recognition chiral extraction (MRCE) system into BRCE system, the enantioselectivity increases from 1.501 to 2.862. The maximum enantioselectivity for H₂A enantiomers is obtained at pH≤2.5 and the ratio of 2:1 of [l-(+)-iso-butyl tartrate] to [HP-β-CD]. The experimental results show that BRCE is of much stronger chiral separation ability than MRCE, which is due to utilization of the separation abilities of both tartrate and β-CD derivative. It may be very helpful to optimize the extraction systems and realize the large-scale production of pure enantiomers.     

Determination of Kinetics in Biphasic Recognition Chiral Extraction for Separation of Phenylsuccinic Acid Enantiomers

This paper reports on the determination of the intrinsic kinetics in biphasic recognition chiral extraction of phenylsuccinic acid enantiomers (H₂A) by L-IBTA and HP-β-CD in a modified Lewis cell. The two-phase homogeneous reaction model was selected, because there is a finite physical solubility of phenylsuccinic acid enantiomers in both the aqueous phase and the organic phase. The regime analysis was split up in three parts: a regime analysis on the aqueous phase reaction in the absence of organic phase reaction, a regime analysis of the organic phase reaction in the absence of the aqueous phase reaction, and a regime analysis of reactions in both phases. The reactions have been found to be first order with respect to H₂A and second order with respect to L-IBTA and HP-β-CD. Competitive extraction of H₂A enantiomers with HP-β-CD and L-IBTA has great influence on the extraction process. With increase of HP-β-CD concentration, high enantioselectivity was obtained, but the extraction rate decreases.     

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.     

反应萃取分离2-苯基丁酸对映体的动力学

通过恒界面池法进行了羟乙基-β-环糊精反应萃取2-苯基丁酸对映体的动力学研究。采用双膜理论和均相反应模型描述了萃取过程的相际传质机理,并考察了搅拌速率、界面面积、对映体初始浓度和萃取剂初始浓度等因素对2-苯基丁酸对映体的萃取动力学的影响。实验结果表明羟乙基-β-环糊精与2-苯基丁酸对映体之间的包合反应属于“快反应”;2-苯基丁酸对映体反应分级数为1,羟乙基-β-环糊精反应分级数为2;（+）-2-苯基丁酸和（-）-2-苯基丁酸在278 K下的反应速率常数分别为2.829×10^-4、1.803×10^-4 m⁶·mol^-2·s^-1。该萃取动力学研究为大规模生产中的反应萃取过程的设计和操作以及设备的设计和过程强化提供了科学的依据。     

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.     

Reaction kinetics in reactive extraction for chiral separation of α-cyclohexyl-mandelic acid enantiomers with hydroxypropyl-β-cyclodextrin

This paper reports on determination of the intrinsic reaction kinetics in reactive extraction of α-cyclohexyl-mandelic acid (α-CHMA) enantiomers with hydroxypropyl-β-cyclodextrin (HP-β-CD) in a modified Lewis cell, in which HP-β-CD dissolved in 0.1 mol/l NaH₂PO₄/H₃PO₄ buffer solution was selected as chiral extractant. α-CHMA enantiomers were extracted from an organic phase to an aqueous phase in the extraction module. The theory of extraction accompanied by chemical reactions has been used to obtain the intrinsic kinetics of this extraction module. The different factors affecting the extraction rate, such as agitation speed, interfacial area, initial enantiomers concentration in an organic phase as well as HP-β-CD concentration in an aqueous phase were separately studied. The experimental results demonstrate that the extraction reaction kinetics is fast. The reactions between α-CHMA enantiomers and HP-β-CD in a stirred cell fall in regime 3 and are first order with respect to α-CHMA enantiomers and second order with respect to HP-β-CD with forward rate constants of 6.9×10⁻² m⁶/(mol² s) and 2.5×10⁻² m⁶/(mol² s) for S-α-CHMA and R-α-CHMA, respectively. These data will be useful in the design of the extraction process.     

Enantioselective Extraction of Racemic Mandelic Acid by Di(2‐ethylhexyl) Phosphoric Acid and Tartaric Acid Derivatives as Mixed Complex Chiral Selectors

The distribution behavior of mandelic acid (MA) enantiomers was examined in a two‐phase system containing di(2‐ethylhexyl) phosphoric acid (D2EHPA) with two tartaric acid derivatives as complex chiral selectors in n‐octanol. Factors affecting the extraction were investigated, including the structure and concentration of tartaric acid as well as the concentration of D2EHPA and D,L‐MA. The results showed that both the distribution ratio and enantioselectivity were greatly improved by using a complex chiral selector rather than using the tartaric acid derivative by itself. Finally, it was found that the formation of mixed complex chiral selectors by mixing two tartaric acid derivatives with D2EHPA can improve the capacity of enantioselective extraction.     

Application and Comparison of High-Speed Countercurrent Chromatography and High Performance Liquid Chromatography in Preparative Enantioseparation of α-Substitution Mandelic Acids

This paper is mainly about extending research on application and comparison of preparative high-speed countercurrent chromatography (HSCCC) and preparative high performance liquid chromatography (HPLC) in chiral separations. Preparative enantioseparations of α-cyclopentylmandelic acid and α-methylmandelic acid by HSCCC and HPLC were compared using hydroxypropy-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD) as the chiral mobile phase additives. In preparative HPLC the enantioseparation was achieved on the ODS C₁₈ reverse phase column with the mobile phase composed of a mixture of acetonitrile and 0.10 mol L^?1 phosphate buffer at pH 2.68 containing 20 mmol L^?1 HP-β-CD for α-cyclopentylmandelic acid and 20 mmol L^?1 SBE-β-CD for α-methylmandelic acid. The maximum sample size for α-cyclopentylmandelic acid and α-methylmandelic acid was only about 10 mg and 5 mg, respectively. In preparative HSCCC the enantioseparations of these two racemates were performed with the two-phase solvent system composed of n-hexane-methyl tert.-butyl ether-0.1 molL^?1 phosphate buffer solution at pH 2.67 containing 0.1 mol L^?1 HP-β-CD for α-cyclopentylmandelic acid (8.5:1.5:10, v/v/v) and 0.1 mol L^?1 SBE-β-CD for α-methylmandelic acid (3:7:10, v/v/v). Under the optimum separation conditions, totally 250 mg of racemic α-cyclopentylmandelic acid could be completely enantioseparated by HSCCC with HP-β-CD as a chiral mobile phase additive in a single run, yielding 114-116 mg of enantiomers with 98-99% purity and 89-92% recovery. But, no complete enantioseparation of α-methylmandelic acid was achieved by preparative HSCCC with either of the chiral selectors due to their limited enantioselectivity. In this paper, preparative enantioseparation by HSCCC and HPLC was compared from various aspects.