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Synthesis 2005(10): 1555-1568  
DOI: 10.1055/s-2005-869903
REVIEW
© Georg Thieme Verlag Stuttgart · New York

Resolution of Enantiomers by Non-Conventional Methods

Elemér Fogassy*a, Mihály Nógrádi*b, Emese Pálovicsc, József Schindlerc
a Institute for Organic Chemical Technology, Technical University of Budapest, P.O.Box 91, Budapest, Hungary
b Institute for Organic Chemistry, Technical University of Budapest, P.O.Box 91, Budapest, Hungary
c Research Group for Organic Chemical Technology, Budapest University of Technology and Economics, P.O.Box 91, Budapest, Hungary
Fax: +36(1)2463648; e-Mail: epalo@mail.bme.hu;
Further Information

Publication History

Received 12 January 2005
Publication Date:
18 May 2005 (online)

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Abstract

Despite unprecedented advances in enantioselective synthesis and separation techniques, large scale production of enantiopure substances, such as required by the pharmaceutical and pesticide industries, is still heavily dependent upon the separation of diastereomers obtained from the enantiomers and an optically active resolving agent. Economy of the process can be much enhanced when only a half-equivalent of the resolving agent is used. Substitution of the other half-equivalent by some achiral compound, as well as separation of the unreacted portion of the substrate from the diastereomer by various physical methods, is discussed. Methods for selecting optimal conditions of resolution and for the purification of partially resolved mixtures are also discussed.

  • 1 Introduction and Historical Background

  • 2 Resolution Methods Using a Half-Equivalent of Resolving Agent

  • 3 Selection of the Optimal Resolving Agent and Solvent

  • 4 Phase Transformations of Diastereomeric Salts or Complexes (Kinetic and Thermodynamic Control)

  • 5 Resolution by Formation of Covalently Bound Diastereo­mers

  • 6 Racemization of an Unwanted Enantiomer

  • 7 Deracemization

  • 8 Resolution of Conglomerate-Forming Racemates by Induced Crystallization

  • 9 Purification of Partially Resolved Mixtures by Crystallization of Conglomerate-Forming and Racemic-Phase-Forming Compounds

  • 10 Purification of a Partially Resolved Mixture of Racemic-Phase-Forming Enantiomers by Fractional Precipitation

  • 11 Resolution by Supercritical Fluid Extraction or Distillation

  • 12 The Non-Linear Character of the Resolution Processes

Key words

resolution of enantiomers - half-equivalent methods - choice of optimal conditions

1

Present-day nomenclature will be used throughout this review.

3

Catalog prices, 2004: (R)-1,1′-binaphthol: ı 44/g; (R)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (BINAP): ı 335/g; (-)-α-pinene: ı 12/g; (+)-α-pinene: ı 13/g; (+)-1,4-bis(diphenylphospino)-1,4-dideoxy-2,3-O-isopropylidene-d-threitol [(+)-DIOP]: ı 118/g; (R,R)-tartaric acid: ı 46/100 g; (S,S)-tartaric acid: ı 70/100 g; dibenzoyl-(R,R)-tartaric acid: ı 81/100 g; (S)-lactic acid: ı 33/kg; (R)-1-phenylethylamine: ı 82/100 mL; (R)-1-phenylethylamine: ı 84/100 g; brucine hydrate: ı 83/100 g; quinine: ı112/100 g.