Crystallization of enantiomers

Abstract Pure enantiomers are of large interest for several industries. Chemical synthesis is frequently not selective and provides racemic mixtures causing a large interest in efficient separation processes. Preparative chromatography is nowadays a powerful and flexible but expensive technology. As an alternative there exists the possibility to apply cheaper crystallization processes. Based on classifying enantiomeric systems according to their type of solid–liquid equilibria, crystallization processes will be discussed which are capable to provide pure enantiomers. Two separation problems studied in our laboratory will be considered for illustration. Preferential crystallization was used to separate racemic threonine dissolved in water. Cooling crystallization was applied to separate a non-racemic solution of mandelic acid enantiomers dissolved also in water.

[1]  Andreas Seidel-Morgenstern,et al.  Solubility Equilibria in Chiral Systems and Their Importance for Enantioseparation , 2003 .

[2]  A. Mersmann Crystallization Technology Handbook , 2001 .

[3]  J. Nývlt,et al.  The Kinetics of industrial crystallization , 1984 .

[4]  A. Seidel-Morgenstern,et al.  Enantiomeric mandelic acid system-melting point phase diagram and solubility in water , 2002 .

[5]  A. Seidel-Morgenstern,et al.  Impact of adsorption isotherm parameters on the performance of enantioseparation using simulated moving bed chromatography. , 2002, Journal of chromatography. A.

[6]  G. Subramanian,et al.  Chiral separation techniques : a practical approach , 2001 .

[7]  Stephen Stinson,et al.  CHIRAL PHARMACEUTICALS: Drug firms continue to develop chiral drugs as single enantiomers, to carry out racemic switches, and to use chirality to manage drug life cycles , 2001 .

[8]  A. Seidel-Morgenstern,et al.  Coupling of simulated moving bed chromatography and fractional crystallisation for efficient enantioseparation. , 2001, Journal of chromatography. A.

[9]  M. Morbidelli,et al.  Simulated moving-bed chromatography and its application to chirotechnology. , 2000, Trends in biotechnology.

[10]  A. Seidel-Morgenstern,et al.  Crystal Growth Kinetics via Isothermal Seeded Batch Crystallization: Evaluation of Measurement Techniques and Application to Mandelic Acid in Water , 2005 .

[11]  Andreas Seidel-Morgenstern,et al.  Binary and ternary phase diagrams of two enantiomers in solvent systems , 2002 .

[12]  D. Grant,et al.  Effect of the opposite enantiomer on the physicochemical properties of (−)-ephedrinium 2-naphthalenesulfonate crystals , 1993 .

[13]  Malte Kaspereit,et al.  Shortcut method for evaluation and design of a hybrid process for enantioseparations. , 2005, Journal of chromatography. A.

[14]  Veronica M. Profir,et al.  Processes and phenomena of purity decrease during the optical resolution of dl-threonine by preferential crystallization , 2000 .

[15]  J. Strube,et al.  Preparative enantioseparation by simulated moving bed chromatography. , 2001, Journal of chromatography. A.

[16]  A. Myerson Handbook of Industrial Crystallization , 2002 .

[17]  A. Rouhi CHIRAL BUSINESS: Fine chemicals companies are jockeying for position to deliver the increasingly complicated chiral small molecules of the future , 2003 .

[18]  Andreas Seidel-Morgenstern,et al.  Experimental study and simplified mathematical description of preferential crystallization. , 2005, Chirality.

[19]  Andreas Seidel-Morgenstern,et al.  Coupling Chromatography and Crystallization for Efficient Separations of Isomers , 2005 .

[20]  G. Sheldrake,et al.  Developments in the commercial manufacture and applications of optically active compounds , 1995 .

[21]  Reginald B. H. Tan,et al.  Recovery of (−)-praziquantel from racemic mixtures by continuous chromatography and crystallisation , 1995 .

[22]  E. Francotte,et al.  Enantioselective chromatography as a powerful alternative for the preparation of drug enantiomers. , 2001, Journal of chromatography. A.

[23]  A. Randolph,et al.  Theory of Particulate Processes: Analysis and Techniques of Continuous Crystallization , 1971 .

[24]  M. Matsuoka Purity Drop in Optical Resolution of Racemic Mixtures , 1997 .

[25]  Veronica M. Profir,et al.  Influence of Solvent and the Operating Conditions on the Crystallization of Racemic Mandelic Acid , 2004 .

[26]  G. Coquerel Review on the heterogeneous equilibria between condensed phases in binary systems of enantiomers. , 2001, Enantiomer.

[27]  H. Miyazaki,et al.  Successive optical resolution by replacing crystallization of DL‐threonine , 1994 .

[28]  A. Seidel-Morgenstern,et al.  Online monitoring of preferential crystallization of enantiomers. , 2004, Chirality.

[29]  A. Maureen Rouhi,et al.  Chirality at work , 2003 .

[30]  A. Seidel-Morgenstern,et al.  A contribution to the mandelic acid phase diagram , 2004 .

[31]  M. Doyle,et al.  Basic Organic Stereochemistry , 2001 .

[32]  G. Subramanian A practical approach to chiral separations by liquid chromatography , 1994 .

[33]  Doraiswami Ramkrishna,et al.  Population Balances: Theory and Applications to Particulate Systems in Engineering , 2000 .

[34]  Andreas Seidel-Morgenstern,et al.  Scale up in preparative chromatography , 1996 .

[35]  W. Lindner,et al.  Separation of enantiomers: needs, challenges, perspectives. , 2001, Journal of chromatography. A.