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How to Use Pasteur’s Tweezers

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Advances in Organic Crystal Chemistry

Abstract

Pasteur introduced two techniques to separate enantiomers. The common visual imagery is that of the first technique, which pertains to the use of tweezers to separate the mirror image crystals of a tartaric acid salt. A second method discovered thereafter, not restricted to the conglomerates necessary for the tweezer approach, is diastereomeric resolution. In this chapter, a short discussion is given of the basic principles of diastereomeric resolutions followed by short analysis of Dutch Resolution, a method based on the use of families of resolving agents. The role of specific nucleation inhibition is discussed. Attention is then turned to conglomerates. Preferential crystallisation is discussed briefly. Particular attention is paid to the discovery of near-equilibrium methods to separate (racemisable) conglomerates by employment of constant attrition of the growing crystals. This methodology has been extended to preparation of the chiral components of some major drugs, and the methodology has also been adapted to separation of non-racemisable conglomerates.

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Notes

  1. 1.

    For cogent summaries of the Pasteur story, see [3, 4]. For a discussion of the behaviour of the Pasteur salt, see [5].

  2. 2.

    A recently published organic textbook with an alternative approach continues to emphasise this story with enthusiasm [6]. As do more classical texts, see, for example, Vollhardt and Schore [7]. For a discussion of the value of visual images in a modern historical different context, see Synder and Judt [8].

  3. 3.

    Undoubtedly, the best general discussion of diastereomeric resolutions and related matters including the history is that of Jacques et al. [12].

  4. 4.

    For a brief and clear discussion of Ostwald ripening and the Gibbs-Thompson effect, see Mullin [13] and Ostwald Ripening [14]. The Ostwald rule of stages, namely, attainment of the final crystal form through a sequence of transient metastable states, is a related, but different, phenomenon; see also Mullin [13]; for a dramatic illustration of Ostwald ripening in the form of huge crystals, see [15], for information about the huge CaSO4°2H2O crystals found in this cave in Mexico, which illustrate dramatically Ostwald ripening.

  5. 5.

    For an extremely early report on the problem of reaching equilibrium during crystallisation, see van’t Hoff [16].

  6. 6.

    For a general discussion of this problem and resolutions in general, see Kellogg and Leeman [24].

  7. 7.

    For an excellent tutorial on use and significance of phase diagrams, see Coquerel [29]; for an older, but excellent, discussion of the basics of the use of phase diagrams, see Jacques et al. [12, 9]. A very detailed discussion of phase diagrams and manner of presentation is given [30].

  8. 8.

    A particularly interesting new development is the Pasteurian resolution of trans-1,2-diaminocyclohexane on the surface of highly organised pyrolytic graphite (HOPG). It is clear that the concept of diastereomeric resolution can clearly be extended to two dimensional surfaces [38].

  9. 9.

    The left-handed and colour-blind author of this chapter confesses to bias with regard to this subject. These “significant minority” afflictions are frequently found together; see, for example, [41].

  10. 10.

    For a cogent discussion of reflection symmetry breaking in general and application to liquid crystals in particular, see Walba [44].

  11. 11.

    For a recent reference and compilation of much earlier work, see Stöhr et al. [49].

  12. 12.

    (S)-clopidogrel (Plavix) is a platelet aggregation inhibitor and is used for treatment of ischemic strokes, heart attacks and atherosclerosis as well as for prevention of thrombosis after placement of intracoronary artery stents. The market was reported to be $9.3 billion in 2010.

  13. 13.

    For a discussion of how Ostwald ripening could work and operate in attrition induced deracemisation, see McLaughlin et al. [74].

  14. 14.

    The following is a non-exhaustive list of articles on the possible mechanism of deracemisation whereby cluster forming is essential [77–83].

  15. 15.

    For an opposing view, see [84, 85] and references contained therein.

  16. 16.

    The mechanism of chiral growth of crystals of NaClO3, NaBrO3 and threonine has recently been investigated by use of dyes [86].

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    Richard M. Kellogg

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    Rui Tamura

  2. The Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan

    Mikiji Miyata

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Kellogg, R.M. (2015). How to Use Pasteur’s Tweezers. In: Tamura, R., Miyata, M. (eds) Advances in Organic Crystal Chemistry. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55555-1_21

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