Gas Antisolvent Fractionation: A New Approach for the Optical Resolution of 4-chloromandelic Acid

Authors

  • Amit Zodge ORCID
    Affiliation

    Department of Chemical and Environmental Process Engineering, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary

  • Márton Kőrösi
    Affiliation

    Department of Chemical and Environmental Process Engineering, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary

  • János Madarász
    Affiliation

    Department of Inorganic and Analytical Chemistry, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary

  • Imre Miklós Szilágyi ORCID
    Affiliation

    Department of Inorganic and Analytical Chemistry, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3.,Hungary

  • Erzsébet Varga
    Affiliation

    CycloLab Cyclodextrin Research and Development Laboratory Ltd., H-1097 Budapest, Illatos út 7., Hungary

  • Edit Székely ORCID
    Affiliation

    Department of Chemical and Environmental Process Engineering, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary

https://doi.org/10.3311/PPch.12910

Abstract

A new, rapid optical resolution method of 4-chloromandelic acid is presented using (R)-1-phenylethanamine as the resolving agent. Gas antisolvent fractionation was investigated as the separation method, studying the effect of pressure, temperature and carbon dioxide to organic solvent mass ratio in details. Generally, the method offers green operation using supercritical carbon dioxide as the precipitative agent, and can be less time- and organic solvent-intensive than conventional processes. By upscaling, the possibility of controlling the crystal-morphology might also be improved. At 16 MPa, 40 °C and 7.5 carbon dioxide to methanol ratio 72 % enantiomeric excess was reached in the crystalline product, along a 73 % yield. The resolution efficiency was not affected by any of the operational parameters. Enantiomeric enrichment beyond 90 % can be carried out by repeated resolution of a scalemic mixture of the acid. Solid products were investigated using differential scanning calorimetry, powder X-ray diffraction and scanning electron microscopy confirming the formation of a crystalline (R)-1-phenylethanammonium-4-chloromandelate salt.

Keywords:

chiral, enantiomer, supercritical, carbon dioxide, optical resolution

Published Online

2019-03-18

How to Cite

Zodge, A., Kőrösi, M., Madarász, J., Szilágyi, I. M., Varga, E., Székely, E. “Gas Antisolvent Fractionation: A New Approach for the Optical Resolution of 4-chloromandelic Acid”, Periodica Polytechnica Chemical Engineering, 63(2), pp. 303–311, 2019. https://doi.org/10.3311/PPch.12910

Issue

Section

Articles