Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter September 17, 2013

Equilibrium of chiral extraction of 4-nitro-d,l-phenylalanine with BINAP metal complexes

Jia-Jia Liu, Guo-Hui Wu, Ke-Wen Tang, Xiong Liu and Pan-Liang Zhang
From the journal Chemical Papers


The enantioselective extraction of 4-nitro-phenylalanine (Nphy) was studied with metal-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) complexes as the chiral selector. The complex with palladium (BINAP-Pd) exhibits the highest selectivity out of the selectors studied, which is solubilised in the organic phase and preferentially extracts d-Nphy from the aqueous phase. Efficiency of extraction depends, often substantially, on a number of process variables, including types of organic solvents and metal precursors, concentration of ligand, pH, and temperature. A reactive extraction model was established to interpret the experimental data. The equilibrium formation constants and other important parameters required by the model were determined experimentally. The equilibrium formation constants were 6.73 and 1.93 for d-Nphy and l-Nphy. By way of modelling and experiment, an optimal extraction condition with pH of 7 and BINAP-Pd concentration of 1 mmol L−1 was obtained with enantioselectivity (α) of 3.37, which was close to the maximum of 3.48, and a performance factor (pf) of 0.195. The model was verified experimentally with excellent results.

[1] Atkins, P. W. (1994). Physical chemistry (5th ed.). New York, NY, USA: Oxford University Press. Search in Google Scholar

[2] Bora, M. M., Ghosh, A. C., Dutta, N. N., & Mathur, R. K. (1997). Reactive extraction of 6-aminopenicillanic acid with aliquat-336: Equilibrium and kinetics. Canadian Journal of Chemical Engineering, 75, 520–526. DOI: 10.1002/cjce.5450750305. in Google Scholar

[3] Davankov, V. A. (1994). Chiral selectors with chelating properties in liquid chromatography: Fundamental reflections and selective review of recent developments. Journal of Chromatography A, 666, 55–76. DOI: 10.1016/0021-9673(94)80 370-6. in Google Scholar

[4] Garcia-Chavez, L. Y., Shazad, M., Schuur, B., & de Haan, A. B. (2012). (Liquid + liquid) equilibrium data for the system (propyleneglycol + water + tetraoctyl ammonium 2-methyl-1-naphthoate). Journal of Chemical Thermodynamics, 55, 238–244. DOI: 10.1016/j.jct.2012.04.002. in Google Scholar

[5] Gutierrez, J. P., Meindersma, W., & de Haan, A. B. (2011). Binary and ternary (liquid + liquid) equilibrium for {methylcycloexane (1) + toluene (2) + 1-hexyl-3-methylimidazolium tetracyanoborate (3)/1-butyl-3-methylimidazolium tetracyanoborate (3)}. Journal of Chemical Thermodynamics, 43, 1672–1677. DOI: 10.1016/j.jct.2011.05.029. in Google Scholar

[6] Hödl, H., Schmid, M. G., & Gübitz, G. (2008). Chiral separation of amino acids and glycyl dipeptides by chiral ligand-exchange capillary electrophoresis comparing Cu(II), Co(II), Ni(II) and Zn(II) complexes of three different sugar acids. Journal of Chromatography A, 1204, 210–218. DOI: 10.1016/j.chroma.2008.05.071. in Google Scholar

[7] Jiao, F. P., Chen, X. Q., Hu, W. G., Ning, F. R., & Huang, K. L. (2007). Enantioselective extraction of mandelic acid enantiomers by L-dipentyl tartrate and β-cyclodextrin as binary chiral selectors. Chemical Papers, 61, 326–328. DOI: 10.2478/s11696-007-0041-4. in Google Scholar

[8] Jira, T., Bunke, A., Schmid, M. G., & Gübitz, G. (1997). Chiral resolution of diols by capillary electrophores using boratecyclodextrin complexation. Journal of Chromatography A, 761, 269–275. DOI: 10.1016/s0021-9673(96)00836-9. in Google Scholar

[9] Keurentjes, J. T. F., Nabuurs, L. J. W. M., & Vegter, E. A. (1996). Liquid membrane technology for the sepapation of racemic mixtures. Journal of Membrane Science, 113, 351–360. DOI: 10.1016/0376-7388(95)00176-x. in Google Scholar

[10] Kodama, S., Yamamoto, A., Matsunaga, A., & Hayakawa, K. (2001). Direct chiral resolution of tartaric acid in food products by ligand exchange capillary electrophoresis using copper(II)-D-quinic acid as a chiral selector. Journal of Chromatography A, 932, 139–143. DOI: 10.1016/s0021-9673(01)01228-6. in Google Scholar

[11] Koska, J., & Haynes, C. A. (2001). Modelling multiple chemical in chiral partition systems. Chemical Engineering Science, 56, 5853–5864. DOI: 10.1016/s0009-2509(00)00419-x. in Google Scholar

[12] Koska, J., Mui, C., & Haynes, C. A. (2001). Solvent effects in chiral ligand exchange systems. Chemical Engineering Science, 56, 29–41. DOI: 10.1016/s0009-2509(00)00418-8. in Google Scholar

[13] Matsumoto, K., Okamoto, T., & Otsuka, K. (2004). Optical resolution of acyclic α-hydroxy ketone derivatives by inclusion complexation. Bulletin of the Chemical Society of Japan, 77, 2051–2056. DOI: 10.1246/bcsj.77.2051. in Google Scholar

[14] Maximini, A., Chmiel, H., Holdik, H., & Maier, N. W. (2006). Development of a supported liquid membrane process of separating enantiomers of N-protected amino acid derivatives. Journal of Membrane Science, 276, 221–231. DOI: 10.1016/j.memsci.2005.09.050. in Google Scholar

[15] Mishra, A. K., Panwar, P., Chopra, M., Sharma, R. K., Chatal, J. F. (2003). Synthesis of novel bifunctional Schiff-base ligands derived from condensation of 1-(p-nitrobenzyl)ethylenediamine and 2-(p-nitrobenzyl)-3-monooxo-1,4,7-triazaheptane with salicylaldehyde. New Journal of Chemistry, 27, 1054–1058. DOI: 10.1039/b300621m. in Google Scholar

[16] Miyamoto, H., Sakamoto, M., Yoshioka, K., Takaoka, R., & Toda, F. (2000). Resolution of hydrocarbons by inclusion complexation with a chiral host compound. Tetrahedron: Asymmetry, 11, 3045–3048. DOI: 10.1016/s0957-4166(00)00269-x. in Google Scholar

[17] Okudomi, M., Shimojo, M., Nogawa, M., Hamanaka, A., Taketa, N., & Matsumoto, K. (2007). Easy separation of optically active products by enzymatic hydrolysis of soluble polymer-supported substrates. Tetrahedron Letters, 48, 8540–8543. DOI: 10.1016/j.tetlet.2007.09.141. in Google Scholar

[18] Quallich, G. J. (2005). Development of the commercial process for Zoloft®/sertraline. Chirality, 17, S120–S126. DOI: 10.1002/chir.20113. in Google Scholar PubMed

[19] Sassatelli, M., Debition, É., Aboab, B., Prudhomme, M., & Moreau, P. (2006). Synthesis and antiproliferaties activies of indolin-2-one derivatives bearing amino acid moieties. European Journal of Medicinal Chemisty, 41, 709–716. DOI: 10.1016/j.ejmech.2006.03.021. in Google Scholar PubMed

[20] Schlichting, E., Halwachs, W., & Schügerl, K. (1987). Reactive extraction of salicylic acid and D,L-phenylalanine in a stirred cell. Chemical Engineering Communication, 51, 193–205. DOI: 10.1080/00986448708911843. in Google Scholar

[21] Schuur, B., Winkelmam, J. G. M., & Heeres, H. J. (2008). Equilibrium studies on enantioselective liquid-liquid amino acid extraction using a cinchona alkaloid extractant. Industrial & Engineering Chemistry Research, 47, 10027–10033. DOI: 10.1021/ie800668e. in Google Scholar

[22] Schuur, B., Winkelman, J. G. M., de Vries, J. G., & Heeres, H. J. (2010). Experimental and modeling studies on the enantioseparation of 3,5-dinitrobenzoyl-(R),(S)-leucine by continuous liquid-liquid extraction in a cascade of centrifugal contactor separators. Chemical Engineeering Science, 65, 4682–4690. DOI: 10.1016/j.ces.2010.05.015. in Google Scholar

[23] Schuur, B., Verkuijl, B. J. V., Minnaard, A. J., de Vries, J. G., Heeres, H. J., & Feringa, B. L. (2011). Chiral separation by enantioselective liquid-liquid extraction. Organic & Biomolecular Chemistry, 9, 36–51. DOI: 10.1039/c0ob00610f. in Google Scholar

[24] Steensma, M., Kuipers, N. J. M., de Haan, A. B., & Kwant, G. (2006). Influence of process parameters on extraction equilibria for the chiral separation of amines and amino-alcohols with a chiral crown ether. Journal of Chemical Technology and Biotechnology, 81, 588–597. DOI: 10.1002/jctb.1434. in Google Scholar

[25] Steensma, M., Kuipers, N. J. M., de Haan, A. B., & Kwant, G. (2007a). Analysis and optimization of enantioselective extraction in a multi-product environment with a multistage equilibrium model. Chemical Engineering and Processing: Process Intensification, 46, 996–1005. DOI: 10.1016/j.cep.2007.05.008. in Google Scholar

[26] Steensma, M., Kuipers, N. J. M., de Haan, A. B., & Kwant, G. (2007b). Modelling and experimental evalution of reaction kinetics in reactive extraction for chiral separation of amines, amino acids and amino-alcohols. Chemical Engineering Science, 62, 1395–1407. DOI: 10.1016/j.ces.2006.11.043. in Google Scholar

[27] Tang, K. W., & Zhang, P. L. (2011). Enantioselective extraction of terbutaline enantiomers with β-cyclodextrin derivaties as hydrophilic selectors. Chemical Papers, 65, 273–279. DOI: 10.2478/s11696-011-0011-8. in Google Scholar

[28] Tang, K. W., Zhang, P. L., Pan, C. Y., & Li, H. J. (2011). Equilibrium studies on enantioselective extraction of oxybuynin enantiomers by hydrophilic β-cyclodextrin derivatives. AIChE Journal, 57, 3027–3036. DOI: 10.1002/aic.12513. in Google Scholar

[29] Tang, K. W., Wu, G. H., Zhang, P. L., Zhou, C. S., & Liu, J. J. (2012). Experimental and model study on enantioseletive extraction of phenylglycine enantiomers with BINAPmetal complexes. Industrial & Engineering Chemistry Research, 51, 15233–15241. DOI: 10.1021/ie301976h. in Google Scholar

[30] Tombo, G. M. R., & Belluš, D. (1991). Chirality and crop protection. Angewandte Chemie International Edition, 30, 1193–1251. DOI: 10.1002/anie.199111933. in Google Scholar

[31] Tsunoda, T., Kaku, H., Nagaku, M., & Okuyama, E. (1997). Deracemization of 2-alkylcyclohexanones utilizing host-gust molecular association with optically active host compounds in basic suspension media. Tetrahedron Letters, 38, 7759–7760. DOI: 10.1016/s0040-4039(97)10071-5. in Google Scholar

[32] Verkuijl, B. J. V., Minnaard, A. J., de Vries, J. G., & Feringa, B. L. (2009). Chiral separation of underivatized amino acids by reactive extraction with palladium-BINAP complexes. Journal of Organic Chemistry, 74, 6526–6533. DOI: 10.1021/jo901002d. in Google Scholar PubMed

[33] Zhou, C. S., Xu, P., Tang, K. W., Jiang, X. Y., Yang, T., & Zhang, P. L. (2013). Enantioselective extraction of hydrophilic 2-chloromandelic acid enantiomers by hydroxypropyl-β-cyclodextrin: experiments and modeling. Chemical Papers, 67, 155–163. DOI: 10.2478/s11696-012-1268-6. in Google Scholar

Published Online: 2013-9-17
Published in Print: 2014-1-1

© 2013 Institute of Chemistry, Slovak Academy of Sciences