Skip to main content
SpringerLink
Log in

Modeling and Optimizing the Biphasic Enantioselective Partitioning of 2-Fluoro-phenylalanine Enantiomers with BINAP–Metal Complexes as Chiral Selector

  • Published:
Journal of Solution Chemistry Aims and scope Submit manuscript

Abstract

2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene (BINAP), which is a highly versatile ligand in asymmetric catalysis, can be used as a very promising chiral ligand for synthesis of chiral extractants. This paper reports an enantioselective liquid–liquid extraction system containing (S)-BINAP–metal complex as chiral extractant (selector) to separate the enantiomers of 2-fluoro-phenylalanine (FPA). An interfacial reaction model was established for modeling the equilibrium of the system and excellent agreement between the model predictions and the experimental results was observed. Operation conditions were optimized by modeling and a high enantioselectivity (α op) of 3.64 and performance factor (pf) of 0.1998 was achieved under the optimal extraction conditions, involving pH value of 8, selector concentration of 1 mmol·L−1 and FPA concentration of 2 mmol·L−1 at a temperature of 5 °C. The data presented indicates that the model provides a powerful tool for modeling two-phase enantioselective reactive extraction systems, which is important for designing industrial processes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

Abbreviations

FPA:

2-Fluoro-phenylalanine

BINAP:

2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene

k :

Distribution ratio, org/aq concentration, dimensionless

k D :

Distribution ratio of d-enantiomer, org/aq concentration, dimensionless

k L :

Distribution ratio of l-enantiomer, org/aq concentration, dimensionless

K D :

Complexation equilibrium constant for d-enantiomer, dimensionless

K L :

Complexation equilibrium constant for l-enantiomer, dimensionless

K a :

Acid dissociation constant (mol·L−1)

ee :

Enantiomeric excess, dimensionless

f :

The fraction of an enantiomer extracted into the organic phase, dimensionless

pf :

Performance factor, dimensionless

C :

Total concentration (mol·L−1)

[]:

Equilibrium concentration (mol·L−1)

t :

Temperature (°C)

α :

Enantioselectivity (dimensionless)

D:

d-Enantiomer

L:

l-Enantiomer

w:

Aqueous phase

org:

Organic phase

0:

Initial value

int:

Intrinsic

op:

Operational

total:

Total value

tot:

Total

References

  1. Joshua, D.H., Anjanette, K., Preeti, K., David, S.S., Andrew, J.G.: Enantioselective separation on a naturally chiral surface. J. Am. Chem. Soc. 126, 14988–14994 (2004)

    Article  Google Scholar 

  2. Yang, W., Wang, K., Hu, Y., Shen, F., Feng, J.: Solubility of L-tartaric acid in ethanol, propanol, isopropanol, n-butanol, acetone and acetonitrile. J. Solution Chem. 42, 485–493 (2013)

    Article  CAS  Google Scholar 

  3. Maier, N.M., Franco, P., Lindner, W.: Separation of enantiomers: needs, challenges, perspectives. J. Chromatogr. A 906, 3–33 (2001)

    Article  CAS  Google Scholar 

  4. Balawejder, M., Mossety-Leszczak, B., Poplewska, I., Lorenz, H., Seidel-Morgenstern, A., Piatkowski, W., Antos, D.: Modeling and predictions of solid–liquid equilibria for citalopram oxalate as a representative of a solid solution forming system. Fluid Phase Equilib. 346, 8–19 (2013)

    Article  CAS  Google Scholar 

  5. Pellissier, H.: Recent developments in dynamic kinetic resolution. Tetrahedron 67, 3769–3802 (2011)

    Article  CAS  Google Scholar 

  6. van der Ent, E.M., Thielen, T.P.H., Stuart, M.A.C., van der Padt, A., Keurentjes, J.T.F.: Electrodialysis system for large-scale enantiomer separation. Ind. Eng. Chem. Res. 40, 6021–6027 (2001)

    Article  Google Scholar 

  7. Duan, G., Ching, C.B., Swarup, S.: Kinetic and equilibrium study of the separation of propranolol enantiomers by high performance liquid chromatography on a chiral adsorbent. Chem. Eng. J. 69, 111–117 (1998)

    Article  CAS  Google Scholar 

  8. Tian, M.L., Yan, H.Y., Row, K.H.: Investigation of ofloxacin enantioseparation by ligand exchange chromatography. J. Chem. Technol. Biotechnol. 84, 1001–1006 (2009)

    Article  CAS  Google Scholar 

  9. Zhou, S.Y., Zuo, H., Stobaugh, J.F., Lunte, C.E., Lunte, S.M.: Continuous in vivo monitoring of amino acid neurotransmitters by microdialysis sampling with online derivatization and capillary electrophoresis separation. Anal. Chem. 67, 594–599 (1995)

    Article  CAS  Google Scholar 

  10. Schuur, B., Floure, J., Hallett, A.J., Winkelman, J.G.M., de Vries, J.G., Heeres, H.J.: Continuous chiral separation of amino acid derivatives by enantioselective liquid–liquid extraction in centrifugal contactor separators. Org. Process Res. Dev. 12, 950–955 (2008)

    Article  CAS  Google Scholar 

  11. Schuur, B., Winkelman, J.G.M., Heeres, H.J.: Equilibrium studies on enantioselective liquid–liquid amino acid extraction using a cinchona alkaloid extractant. Ind. Eng. Chem. Res. 47, 10027–10033 (2008)

    Article  CAS  Google Scholar 

  12. Prelog, V., Kovačević, M., Egli, M.: Lipophilic tartaric acid esters as enantioselective ionophores. Angew. Chem. Int. Ed. 28, 1147–1152 (1989)

    Article  Google Scholar 

  13. Viegas, R.M.C., Afonso, C.A.M., Crespo, J.G., Coelhoso, I.M.: Modeling of the enantio-selective extraction of propranolol in a biphasic system. Sep. Purif. Technol. 53, 224–234 (2007)

    Article  CAS  Google Scholar 

  14. Tan, B., Luo, G.S., Wang, J.D.: Extractive separation of amino acid enantiomers with co-extractants of tartaric acid derivative and aliquat-336. Sep. Purif. Technol. 53, 330–336 (2007)

    Article  CAS  Google Scholar 

  15. Pietraszkiewicz, M., Kozbia, M., Pietraszkiewicz, O.: Chiral discrimination of amino acids and their potassium or sodium salts by optically active crown ether derived from D-mannose. J. Membr. Sci. 138, 109–113 (1998)

    Article  CAS  Google Scholar 

  16. Steensma, M., Kuipers, N.J.M., de Haan, A.B., Kwant, G.: Influence of process parameters on extraction equilibria for the chiral separation of amines and amino-alcohols with a chiral crown ether. J. Chem. Technol. Biotechnol. 81, 588–597 (2006)

    Article  CAS  Google Scholar 

  17. Colera, M., Costero, A.M., Gaviña, P., Gil, S.: Synthesis of chiral 18-crown-6-ethers containing lipophilic chains and their enantiomeric recognition of chiral ammonium picrates. Tetrahedron Asymmetry 16, 2673–2679 (2005)

    Article  CAS  Google Scholar 

  18. Hallett, A.J., Kwant, G.J., de Vries, J.G.: Continuous separation of racemic 3,5-dinitrobenzoyl-amino acids in a centrifugal contact separator with the aid of cinchona-based chiral host compounds. Chem. Eur. J. 15, 2111–2120 (2009)

    Article  CAS  Google Scholar 

  19. Tang, K.W., Zhang, P.L., Pan, C.Y., Li, H.J.: Equilibrium studies on enantioselective extraction of oxybutynin enantiomers by hydrophilic β-cyclodextrin derivatives. AIChE J. 57, 3027–3036 (2011)

    Article  CAS  Google Scholar 

  20. Valle, E.M.M.D.: Cyclodextrins and their uses: a review. Process Biochem. 38, 373–377 (2002)

    Article  Google Scholar 

  21. Tang, K.W., Song, L.T., Liu, Y.B., Miao, J.B.: Enantioselective partitioning of 2-phenylpropionic acid enantiomers in a biphasic recognition chiral extraction system. Chem. Eng. J. 180, 293–298 (2012)

    Article  CAS  Google Scholar 

  22. Koska, J., Haynes, C.A.: Modeling multiple chemical equilibria in partition systems. Chem. Eng. Sci. 56, 5853–5864 (2001)

    Article  CAS  Google Scholar 

  23. Verkuijl, B.J.V., Minnaard, A.J., de Vries, J.G., Feringa, B.L.: Chiral separation of underivatized amino acids by reactive extraction with palladium-BINAP complexes. J. Org. Chem. 74, 6526–6533 (2009)

    Article  CAS  Google Scholar 

  24. Tang, L., Choi, S., Nandhakumar, R., Park, H., Chung, H., Chin, J., Kim, K.M.: Reactive extraction of enantiomers of 1,2-amino alcohols via stereoselective thermodynamic and kinetic processes. J. Org. Chem. 73, 5996–5999 (2008)

    Article  CAS  Google Scholar 

  25. Yoon, J., Cram, D.J.: Chiral recognition properties in complexation of two asymmetric hemicarcerands. J. Am. Chem. Soc. 119, 11796–11806 (1997)

    Article  CAS  Google Scholar 

  26. Ding, H.B., Carr, P.W., Cussler, E.L.: Racemic leucine separation by hollow-fiber extraction. AIChE J. 38, 1493–1498 (1998)

    Article  Google Scholar 

  27. Snyder, S.E., Carey, J.R., Pirkle, W.H.: Biphasic enantioselective partitioning studies using small-molecule chiral selectors. Tetrahedron 61, 7562–7567 (2005)

    Article  CAS  Google Scholar 

  28. Kocabas, E., Karakucuk, A., Sirit, A., Yilmaz, M.: Synthesis of new chiral calyx [4] arene diamide derivatives for liquid phase extraction of α-amina acid methylesters. Tetrahedron Asymmetry 17, 1514–1520 (2006)

    Article  CAS  Google Scholar 

  29. Hendry, A.T., Dillon, J.R.: Growth inhibition of Neisseria gonorrhoeae isolates by L-phenylalanine and its analogues in defined media. Can. J. Microbiol. 30, 1319–1325 (1984)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Science Foundation of China (No. 21171054), Key Laboratory of Hunan province, and Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province.

Author information

Authors and Affiliations

  1. Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China

    Panliang Zhang, Kewen Tang, Jie Hua & Ming Zhong

  2. College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, Hunan, China

    Chang Liu & Jiajia Liu

Authors
  1. Panliang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kewen Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiajia Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jie Hua
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ming Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kewen Tang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, P., Liu, C., Tang, K. et al. Modeling and Optimizing the Biphasic Enantioselective Partitioning of 2-Fluoro-phenylalanine Enantiomers with BINAP–Metal Complexes as Chiral Selector. J Solution Chem 44, 112–130 (2015). https://doi.org/10.1007/s10953-014-0287-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10953-014-0287-8

Keywords

Search

Navigation