Equilibrium Studies on Enantioselective LiquidâLiquid Extraction of

Article pubs.acs.org/jced

Equilibrium Studies on Enantioselective Liquid−Liquid Extraction of Phenylalanine Enantiomers Using BINAP−Metal Complexes Kewen Tang,*,† Tao Fu,‡ and Panliang Zhang† †

Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang 414006, Hunan, China College of Chemical Engineering, Xiangtan University, Xiangtan 411105, Hunan, China

‡

ABSTRACT: The deparation of phenylalanine (Phe) enantiomers by reactive liquid−liquid extraction with (s)-BINAP-metal complexes as enantioselective extractants was investigated. Metal complexes formed by different central ions with (s)-BINAP as a ligand were used as chiral extractants, among which the CuPF6-(s)-BINAP complex (BINAP-Cu) allowed the separation of the Phe enantiomers with the highest operational selectivity. The efficiency of the extraction depends, often strongly, on a number of process variables, including the types of metal precursors and organic solvents, pH of the aqueous phase, concentration of extractant and substrate, and temperature. To better understand the extraction process, an interfacial reaction model was established. The best conditions involving a pH value of 7, feed concentration of 2.0·10−3 mol·kg−1, BINAP-Cu concentration of 1.59·10−3 mol·kg−1, and temperature of 5 °C are obtained by modeling and optimization with a high enantioselectivity of 5.2038. The model quantitatively predicts the extraction performance and provides a simple computational approach to process optimization.

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INTRODUCTION The availability of enantiopure compounds is of prime importance for the pharmaceutical industry and also to some extent for the agrochemical, flavor, and fragrance industries.1,2 So the demand for enantiopure compounds is growing rapidly,3 and the investigation on the preparation of enantiopure compounds has attracted lots of attention nowadays.4−8 Asymmetric synthesis is an important method to obtain enantiopure compounds. However, the method involves relatively high cost, is time-consuming, and produces low yield.9 Another kind of method is through chiral separation, including crystallization,8,10,11 chromatography,12 capillary electrophoresis,13 and enantioselective liquid−liquid extraction.14 Enantioselective liquid−liquid extraction is considered as a potentially attractive technique because it is cheaper and easier to scale up to commercial scale and has a large application range.15 Enantioselective extraction of α-amino acid enantiomers is a challenge in the field of enantioselective liquid−liquid extraction. The chiral extractant (selector) is the most important issue, and several chiral extractants have been reported, such as tartaric acid derivatives,16,17 crown ethers,18,19 cinchona alkaloids,20,21 β-CD derivatives,22,23 and so on.24,25 However, the low versatility and/or enantioselectivity of these selectors limits their wider application. So the development of improved chiral selector is essential.26 It has been reported that metal complexes can show good performance in enantioselective extraction.27−29 Chiral bisphosphine BINAP is wellknown as a highly versatile ligand in asymmetric catalysis.30 Using the metal−BINAP complex as a chiral selector has © 2012 American Chemical Society

attracted a lot of interest in the investigation of enantioselective extraction.31,32 Phenylalanine (Figure 1a) is one of the eight essential amino acids for human body. Phe is widely used in medicine, food, and chemical industries. L-Phe is the main raw material of aspartame and an essential ingredient of some medical infusion

Figure 1. Chemical structure of Phe (a) and the BINAP-Cu complex (b). Received: July 31, 2012 Accepted: October 3, 2012 Published: October 24, 2012 3628

dx.doi.org/10.1021/je300846m | J. Chem. Eng. Data 2012, 57, 3628−3635

Journal of Chemical & Engineering Data

Article

phosphate buffer solution (phosphate concentration = 0.1 mol·kg−1, pH = 7.0), and the concentration of racemic Phe was kept at 2.0·10−3 mol·kg−1. The extractant (complex of BINAPCu) was added to 1,2-dichloroethane with concentrations ranging from 0.25·10−3 mol·kg−1 to 2.0·10−3 mol·kg−1. The two phases were put together in a glass centrifuge tube in equal amounts (2 mL) and shaken sufficiently (12 h) before being kept in a water bath at a fixed temperature (24 h) to reach equilibrium. After equilibrium, the composition of the aqueous phase was analyzed by HPLC.

products. It can also be used as the raw material or carrier of some drugs. This paper reports the investigation of enantioselective extraction of Phe enantiomers with the BINAP−metal complex as a chiral selector. Effects of process variables, such as types of the central ions and organic solvents, the pH of aqueous phase, and concentrations of selector and substrate and temperature, on the enantioselective extraction of Phe enantiomers were systematically investigated. A reactive extraction model based on an interfacial ligand exchange mechanism is established. Optimization of the extraction system was carried out by modeling and experiments.

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THEORY AND MODELING Theory of Reactive Extraction. To optimize a reactive extraction process, knowledge of the extraction mechanism is required. The two different types of extraction mechanism that have been proposed for enantioselective liquid−liquid extraction are the homogeneous ligand addition mechanism and the interfacial ligand exchange mechanism.34,35 The main difference between the two models is the locus of the complexation reaction. The interfacial reaction model obviously applies when the reaction take place at the interface. In the reactive extraction of Phe enantiomers by BINAP-Cu complexes, the BINAP-Cu complexes are highly hydrophobic, which exclude the possibility that the reaction takes place in the aqueous phase. Depending on the solubility of Phe enantiomers in the organic phase, the complexation reaction may be limited to the interface or may take place in the organic phase. It is observed from the extraction experiments without extractant that no Phe enantiomers distribute from the aqueous phase to the organic phase. So we have applied the interfacial ligand exchange mechanism in this paper (Figure 2).

EXPERIMENTAL SECTION Chemicals. Bi(acetonitrile)dichloropalladium ((CH3CN)2PdCl2, mass fraction > 99 %) was purchased from Metallurgy Institute of Zhejiang (Zhejiang, China). Bis(triphenylphosphine)nickel(II) ([(C6H5)3P]2NiCl2, mass fraction > 99 %) and tetrakis(acetonitrile)copper(I) hexafluorophosphate ((CH3CN)4CuPF6, mass fraction > 99 %) were purchased from Hewei Chemical Co. Ltd. (Guangzhou, China). (S)-(−)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene ((s)-BINAP, mass fraction > 99 %) was purchased from Shengjia Chemical Co. Ltd. (Heibei, China). Phenylalanine (racemate, mass fraction > 99 %) was purchased from Nantong Chemical (Jiangsu, China). The solvent for chromatography was of HPLC grade. All other chemicals were of analyticalreagent grade and bought from different suppliers. Analytical Method. The concentration of Phe enantiomers in aqueous phase was determined by high-performance liquid chromatography (HPLC) using an Agilent LC 1200 series apparatus (Agilent Technologies Co. Ltd., USA). The column was Inertsill ODS, 3.5 μm particle size of the packing material, 4.6 × 250 mm I.D. (GL Sciences Inc., Japan). The detection wavelength was set at 250 nm. The mobile phase was a mixture of methanol and an aqueous solution containing 0.75·10−3 mol·kg−1 of copper sulfate and 1.5·10−3 mol·kg−1 of L-proline with pH = 5.0 (pH was adjusted with ammonium acetate). The mass fraction of methanol is 0.165. The flow rate was set at 60 mL·h−1. Before sampling from the aqueous phases, a medical centrifuge (operated at 3000 rotations per minute; model: TD4A; supplied by Yingtai Instrument Co. Ltd., Changsha, China) was used to assist the phase separation of all the extraction systems. Extraction Experiments. The racemic Phe was dissolved in sodium phosphate buffer solution (phosphate concentration = 0.1 mol·kg−1), and the obtained solution was used as aqueous phase. The organic phase was prepared by dissolving (s)BIN AP a nd me tal p recu rs ors ( (CH 3 CN) 2 P d C l 2 , [(CH3CN)4Cu]PF6, [(C6H5)3P]2NiCl2) in organic solvent. Aqueous solution (2 mL) and organic solution (2 mL) were put together in a glass centrifuge tube and shaken sufficiently (12 h) before being kept in a water bath at a fixed temperature (24 h) to reach equilibrium. The concentration of Phe enantiomers in aqueous phase was analyzed using HPLC. Because the change of volumes of aqueous and organic phases is very small and can be neglected, the concentration of Phe enantiomers in organic phase can be calculated from mass balance. Determination of Complexation Equilibrium Constants KD and KL. Reactive extraction experiments were carried out to determine the complexation equilibrium constants of BINAP-Cu with Phe enantiomers in the biphasic system (Figure 1b).33 Racemic Phe was dissolved in sodium

Figure 2. Interfacial ligand exchange mechanism of reactive extraction of Phe enantiomers by the BINAP-Cu complex.

Model Equation. Consider an organic phase of volume Vorg in equilibrium with an aqueous phase of volume Vaq. Species in both phases are in chemical equilibrium, and each phase is open with respect to the other. The reactive enantioselective liquid− liquid extraction system could be modeled by a series of coupled equilibrium relations and mass balances as follows. The dissociation constant of ionic D- and L-Phe is Ka =

[D−]w [H+] [L−]w [H+] = [DH]w [LH]w

(1)

The complexation equilibrium of CuPF 6 -(s)-BINAP (BINAP-Cu) with Phe enantiomers in the interface can be written as follows: 3629


Journal of Chemical & Engineering Data KD =

Article

[CuBD]org [PF6−]w

(KDKL − KDA − KLA + A2 )[CuB]3org

−

[CuB]org [D ]w

tot tot tot + (2KDACCuB + 2KLACCuB − 3A2 CCuB + KDKLC Dtot

(2)

[CuBL]org [PF6−]w

KL =

tot − KDC DtotA + KDKLC Ltot − KLC LtotA − KDKLCCuB )

[CuB]org [L−]w

2 tot tot [CuB]org + (KDC DtotACCuB + KLC LtotACCuB

(3)

2

Due to Vaq = Vorg, the following equations represent the mass balance for D- and L-Phe: C Dtot = [DH]w + [D−]w + [CuBD]org

(4)

C Ltot = [LH]w + [L−]w + [CuBL]org

(5)

3

tot − A2 CCuB =0

KD[CuB]org

kD =

{

[PF6−]w 1 +

{

[PF6−]w 1 +

eeorg =

(8)

[CuB]org [L−]w KL +

Let A = {1 + ([H ]/Ka)}, tot CCuB = [CuB]org +

tot tot + C D,org C L,org

=

CL 1 + 1 / kL CL 1 + 1 / kL

− +

CD 1 + 1 / kD CD 1 + 1 / kD

(16)

Citot ,org Citot

(17)

pfi = fi eeorg

[CuB]org KL

(18)

Regression of Complexation Equilibrium Constants. Regression of the complexation equilibrium constants of the complex formed at the interface (Figure 2) was carried out as follows: combining eqs 1 to 3, 12, and 13, the following equation can be achieved:

[PF6−]w KDC Dtot[CuB]org [CuB]org KD + A[PF6−]w

KLC Ltot[CuB]org [CuB]org KL + A[PF6−]w

tot tot − C D,org C L,org

where Ctot i,org represents the total concentration of the solute i in organic phase at equilibrium, and Ctot i represents the initial total concentration of the solute i. The extraction performance factor (pf) is defined as36

[PF6−]w

[CuB]org KL + A[PF6−]w

= [CuB]org + +

can be defined as

C Dtot[PF6−]w [CuB]org KD [CuB]org KD + A[PF6−]w

C Ltot[PF6−]w

+

fi =

(9)

Ctot CuB

(15)

where represents the total concentration of L-Phe in the organic phase; Ctot D,org represents the total concentration of DPhe in the organic phase. The fraction of the solute i (i = D or L) extracted (f i) into the organic phase is given by

[PF6−]w

[PF6 ]w

(14)

Ctot L,org

[CuB]org [D−]w KD

−

(13)

The enantiomeric excess in the organic phase can be expressed in terms of distribution ratio by the following equation:

(7)

Combining eqs 2 to 8, eq 9 is deduced to

+

}

KL KD

a int =

where Ctot CuB is the initial concentration of BINAP-Cu in the organic phase. The [PF6−]w is the concentration of PF6− in the aqueous phase. There is the following equation for mass balance for CCuB:

tot CCuB = [CuB]org +

[H+] {K }a

Intrinsic enantioselectivity is given by

(6)

C Ltot = [LH]w + [L−]w + [CuBL]org

tot CCuB = [CuB]org + [CuBD]org + [CuBL]org

(12)

kL kD

aop =

−

[CuB]org [L−]w KL [L−]w [H+] − = + [L ]w + Ka [PF6−]w

}

Enantioselectivity is given by

= [DH]w + [D ]w + [CuBD]org [CuB]org [D ]w KD [D−]w [H+] + [D−]w + Ka [PF6−]w

[H+] Ka

KL[CuB]org

kL =

−

=

(11)

[CuB]org can be calculated from eq 11, and distribution ratios can be written as follows:

tot where Ctot D and CL are the initial concentrations of D- and L-Phe in the aqueous phase, respectively, and [DH]w and [LH]w are the concentrations of molecular D- and L-Phe in the aqueous phase, [D−]w and [L−]w are the concentrations of anion D- and L-Phe in the aqueous phase. [CuBD]org and [CuBL]org are the concentrations of the complexes of CuPF6-(s)-BINAP with Dand L-Phe in the organic phase; [CuB]org is the concentration of BINAP-Cu in the organic phase at equilibrium. Combining eqs 1 to 3, 6, and 7 are deduced to

C Dtot

2

2 tot tot − CCuB KDA − CCuB KLA + 3A2 CCuB )[CuB]org

AkD2C Dtot(kL + 1) + AkDkLC Ltot(kD + 1) (10)

tot = KD[CCuB (kD + 1)(kL + 1) − kDC Dtot(kL + 1)

With a further treatment of eq 10, the following equation can be deduced

− kLC Ltot(kD + 1)] 3630

(19)



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Table 1. Influence of Metal Precursor Typea

AkL2C Ltot(kD + 1) + AkDkLC Dtot(kL + 1) tot = KL[CCuB (kD + 1)(kL + 1) − kDC Dtot(kL + 1)

− kLC Ltot(kD + 1)]

(20)

By linear regression of the experimental data according to eqs 19 and 20, the equilibrium constants, KD and KL, are evaluated from the slope of the fitting lines.

metal precursor

kD

kL

α

(CH3CN)2PdCl2 (CH3CN)4CuPF6 [(C6H5)3P]2NiCl2

0.6698 0.1260 0.1264

0.2905 0.5295 0.1153

2.3058 4.2029 1.0964

Conditions: solvent = dichloromethane, T = 5 °C, pH = 7.0, ligand = (s)-BINAP, [metal precursor]0 = 0.796·10−3 mol·kg−1, [ligand]0 = 0.796·10−3 mol·kg−1, [Phe]0 = 2.0·10−3 mol·kg−1.

a

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RESULTS AND DISCUSSION Complexation Equilibrium Constants KD and KL. The complexation equilibrium constants of CuPF6-(s)-BINAP (BINAP-Cu) with D- and L-Phe were determined by a series of reactive extraction experiments as described in the Experimental Section. The experimental data were analyzed as described in the Regression of Complexation Equilibrium Constants Section. We defined B = AkD2Ctot D (kL + 1) + AkDkLCLtot(kD + 1) for D-Phe, B = AkD2CLtot(kD + 1) + tot AkDkLCtot D (kL + 1) for L-Phe, and X = CCuB(kD + 1)(kL + 1) tot tot − kDCD (kL + 1) − kLCL (kD + 1). As shown in Figure 3, the

et al., selectivity was improved considerably by replacing the central ion palladium with copper. This will hold a lot of economic advantages.32 It is also observed from Table 1 that DPhe is the preferred enantiomer when extracted by palladium or nickel BINAP complexes. But when BINAP-Cu complex is used as an extractant, L-Phe is the preferred enantiomer. Because enantioselectivity is the most important factor, (CH3CN)4CuPF6 is chosen as the suitable metal precursor for the extraction of Phe enantiomers. Screening of Organic Solvents. The organic solvent has a clear influence on both distribution ratios and enantioselectivity. The solvent can influence the noncovalent interactions and the conformation of the chiral partners in enantioselective host−guest complexation.35 Distribution ratios and operational selectivity for Phe enantiomers extracted by BINAP-Cu complexes with four different organic solvents are shown in Table 2. When Table 2. Influence of Organic Solvent Typea solvent

kD

kL

α

dichloromethane 1,2-dichloroethane chloroform chlorobenzene

0.0779 0.0857 0.1154 0.1026

0.3628 0.4458 0.3553 0.1709

4.6541 5.2038 3.0789 1.6656

a Conditions: T = 5 °C, pH = 7.0, metal precursor = (CH3CN)4CuPF6, ligand = (s)-BINAP, [metal precursor]0 = 0.796·10−3 mol·kg−1, [ligand]0 = 0.796·10−3 mol·kg−1, [Phe]0 = 2.0·10−3 mol·kg−1.

Figure 3. Plot of B versus X for Phe enantiomers in 1,2dichloroethane/water two-phase system at 5 °C. B = Ak2DCtot D (kL + 2 tot 1) + AkDkLCtot L (kD + 1) for ■, D-Phe and B = AkDCL (kD + 1) + tot tot AkDkLCtot D (kL + 1) for ●, L-Phe; X = CCuB(kD + 1)(kL + 1) − kDCD (kL 2 + 1) − kLCtot (k + 1); ―, line fits; R = 0.986 for D -Phe and R2 = L D 0.981 for L-Phe.

chlorobenzene is used as organic solvent, no significant αop was observed, and distribution ratios are also very low. The aromatic nature of the solvent is likely to influence the enantioselective complexation adversely, suggesting that π−π interactions between Phe enantiomers and BINAP-Cu complex are an important factor in chiral recognition.31 Three halogenated hydrocarbon solvents were also tested, and distribution ratios and enantioselectivities are clearly improved. The highest distribution ratios and enantioselectivity were obtained with 1,2-dichloroethane as the organic solvent. Therefore, 1,2-dichloroethane was chosen as the suitable solvent for the extraction of Phe enantiomers. Influence of pH. The effect of pH of the aqueous phase on the distribution ratios and operational selectivity was investigated. Influence of pH is also predicted by the interfacial reaction model. Comparison of the experimental values with the model predictions is shown in Figure 4. It is observed that experimental values are in good agreement with the model predictions indicating that the interfacial reaction model is capable of predicting the influence of pH. As shown in Figure 4, distribution ratios (kD and kL) increase with the rising of pH in the range of pH = 5 to pH = 7 and then increase slightly when pH > 7. The increased distribution ratios in response to increasing pH may result from the fact that only

plot of B versus X for D-Phe yields a straight line, and the slope of the line was used to evaluate KD as 0.09 (dimensionless quantity). A similar data treatment according to eq 20 can be performed to evaluate KL as 0.46. The intrinsic selectivity αint (KL/KD) is estimated as 5.11. Screening of Metal Precursors. Different extractants synthesized by complexation of (s)-BINAP with different metal precursors were tested for screening of the metal precursors. Distribution ratios (kD and kL) and operational selectivity (αop) with different (s)-BINAP-metal complexes in dichloromethane are shown in Table 1. With (CH3CN)2PdCl2 as a metal precursor, an operational selectivity of 2.306 was obtained. The obtained selectivity is very close with that obtained by Verkuijl et al.32 The lowest distribution and operational selectivity were obtained with [(C6H5)3P]2NiCl2 as metal precursor. The highest selectivity is achieved by using (CH3CN)4CuPF6 as metal precursor and αop of 4.202; a kD and a kL of 0.126 and 0.530 are obtained. When compared with the work of Verkuijl 3631



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Figure 5. Dependence of the distribution and operational selectivity on extractant (BINAP-Cu) concentration. Solid lines: model predictions. Symbols: experimental data: ●, kL; ⧫, kD; ■, operational selectivity. Conditions: T = 5 °C, pH = 7.0, [Phe]0 = 2.0·10−3 mol·kg−1.

Figure 4. Dependence of the distribution and operational selectivity on pH. Solid lines: model predictions. Symbols, experimental data: ●, kL; ⧫, kD; (■) represents operational selectivity. Conditions: T = 5 °C, metal precursor = (CH3CN)4CuPF6, ligand = (s)-BINAP, [metal precursor]0 = 0.796·10−3 mol·kg−1, [ligand]0 = 0.796·10−3 mol·kg−1, [Phe]0 = 2.0·10−3 mol·kg−1.

predictions shown in Figure 5 indicates that influence of the extractant concentration are predicted quite well by the model. It is observed from Figure 5 that kD and kL increase with the increase of extractant concentration while the operational enantioselectivity keeps constant. Phe enantiomers can form complexes with the extractant in organic phase; more complexes are formed in organic phase, and the distribution ratios consequently increase when the extractant concentration is increased. The operational enantioselectivity remains constant when the extractant concentration is increased, and the value of αop is close to αint which shows the model predicts enantioselectivity well. Influence of Temperature. The temperature has a strong influence on the distributions (kD and kL) and operational enantioselectivity (αop) which is shown in Figure 6. The rise in temperature leads to the decrease of distribution ratios and enantioselectivity. It is also observed that kL and αop have an obvious decrease, but kD decreases slightly. The possible reason for a decrease in distribution ratio and enantioselectivity is that the rising temperature weakens the selector−enantiomer

anion Phe binds to the BINAP-Cu complex and no physical partition (distribution ratios of the Phe enantiomers in the reactive extraction system without extractant) was observed in the pH range examined. With pH increasing from 5.0 to 7.0, large amounts of molecular Phe enantiomers are dissociated into anion Phe and form complexes with the extractant in the organic phase. Distribution ratios are therefore increased. When the pH is above 7.0, most of Phe enantiomers exist in anion form, and the amount of anion Phe enantiomers increases only a little, which leads to a slight increase of distribution ratios. It can also be observed from Figure 4 that pH has no influence on the operational enantioselectivity. This fits the predictions well. Influence of Extractant Concentration. The influence of extractant (BINAP-Cu complex) concentration on extraction performance was investigated at pH 7 and temperature of 5 °C. The influence of extractant concentration is also predicted by the model which is presented as solid lines in Figure 5. A comparison of the experimental values with the model 3632



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Figure 6. Dependence of the distribution and operational selectivity on temperature. Symbols: ●, kL; ■ in the top figure, kD; ■ in the bottom figure, operational selectivity. Conditions: solvent: 1,2dichloroethane; metal precursor = [(CH3CN)4CuPF6], ligand = (s)BINAP, [metal precursor]0 = 0.796·10−3 mol·kg−1, [ligand]0 = 0.796·10−3 mol·kg−1, [Phe]0 = 2.0·10−3 mol·kg−1, pH = 7.0.

Figure 7. Calculated distribution ratio for Phe enantiomers as a function of pH and extractant concentration. [Phe]0 = 2.0·10−3 mol·kg−1, temperature = 5 °C, solvent = 1,2-dichloroethane.

interaction and the discrimination ability of the selectors toward Phe enantiomers. Therefore, 5 °C is considered as the optimal temperature. Model Predictions in the Liquid−Liquid Extraction System. A comparison of the experimental values with the model predictions indicates that the interfacial reaction model is capable of predicting enantiomer partitioning over a range of experimental conditions. Therefore, we utilized the model to explore the influence of various operating conditions on extraction performance in a single stage extraction system. In Figure 7, the calculated distribution ratios (kD and kL) for Phe enantiomers as a function of pH and extractant concentration are shown. It can be seen from Figure 7 that kD and kL follow a similar tendency with the change of pH and the extractant concentration. The distribution ratios increase with the increase of pH and extractant concentration. Figure 8 shows the enantiomeric excess (ee) for Phe enantiomers in the organic phase as a function of pH and extractant concentration. When pH value and extractant concentration are low, ee is relatively higher. An increase of extractant concentration and pH value can increase distribution ratios but does not lead to an increase of ee value.

Figure 8. Calculated enantiomeric excess (ee) for Phe enantiomers in the organic phase as a function of pH and extractant concentration. [Phe]0 = 2.0·10−3 mol·kg−1, temperature = 5 °C, solvent = 1,2dichloroethane.

It is difficult to identify the optimal solution conditions for enantiomer resolution from Figures 7 and 8, because of the opposing trends of enantiomeric excess and distribution ratios. To facilitate optimization of the extraction system, the 3633



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performance factor (pf) is introduced. The pf is defined as the product of ee in the organic phase and the fraction of enantiomer extracted into the organic phase. A high performance factor indicates conditions where the given enantiomer can be purified to high purity with a maximum yield.36 Figure 9 shows the performance factors calculated as a function of pH and extractant concentration. The extractant

Figure 11. Performance factors as a function of extractant concentration. Solid lines: model predictions. Symbols: experimental data. Conditions: solvent = 1,2-dichloroethane; metal precursor = (CH3CN)4CuPF6, ligand = (s)-BINAP, [Phe]0 = 2.0·10−3 mol·kg−1, T = 5 °C, pH = 7.0. Figure 9. Calculated performance factor (pf) for Phe enantiomers as a function of pH and extractant concentration. [Phe]0 = 2.0·10−3 mol·kg−1, temperature = 5 °C, solvent = 1,2-dichloroethane.

performance factor increases with the rise in pH and reaches a plateau as pH value of above 7. As shown in Figure 11, the performance factor increases rapidly with the increasing of extractant concentration when extractant concentration is lower than 1.59·10−3 mol·kg−1, but a further increase of extractant concentration leads to only a slight increase of pf. It can be seen from Figures 10 and 11 that the experimental results are in good agreement with the model predictions, including the plateaus shown in Figure 9. These results therefore validate the model and its application for the optimization of the extraction system.

concentration and pH have a strong influence on the performance factor. A relatively high pH and extractant concentration will lead to a relatively high performance factor (pf). There is a plateau in which pH value is above 7 and extractant concentration is more than 1.59·10−3 mol·kg−1. Experimental performance factors were measured to support the model predictions at solution conditions explored in Figure 9. The experimental values and predictions are plotted in Figures 10 and 11 as a function of pH and extractant concentration, respectively. Figure 10 shows that the measured

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CONCLUSIONS The enantioselective reactive extraction of Phe enantiomers by the BINAP−metal complex has been investigated. The extraction performance is influenced by a series of process variables, such as types of organic solvents and metal precursors, concentration of extractant, pH, and temperature. The most suitable organic solvent is 1,2-dichloroethane, and the best selector for chiral separation of Phe enantiomers is the complex of BINAP-Cu. An interfacial ligand exchange model has been developed for modeling the reactive extraction system, and excellent agreement between the model predictions and experimental data was observed. The presented data indicate that the model provides a powerful tool for calculating the distribution ratio, enantioselectivity, enantiomeric excess, and performance factor. Therefore, it can be used for optimization of the reactive extraction systems. The best conditions involve the use of feed concentration of 2.0·10−3 mol·kg−1 and a BINAP-Cu complex concentration of 1.59·10−3 mol·kg−1 in 1,2-dichloroethane, and a pH value of 7 at 5 °C was obtained.

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Figure 10. Performance factors as a function of pH. Solid lines: model predictions. Symbols: experimental data. Conditions: solvent = 1,2dichloroethane; metal precursor = (CH3CN)4CuPF6, ligand = (s)BINAP, [metal precursor]0 = 0.796·10−3 mol·kg−1, [ligand]0 = 0.796·10−3 mol·kg−1, [Phe]0 = 2.0·10−3 mol·kg−1, T = 5 °C.

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Corresponding Author

*Tel.: +86-13762003936; fax: +86-730-8640921. E-mail address: [email protected] (K.W.T.). 3634



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This work was supported by the National Natural Science Foundation of China (No. 21171054), Hunan Provincial Natural Science Foundation of China (No. 10JJ1004), and Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province. Notes

The authors declare no competing financial interest.

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