The Dutch Resolution Variant of the Classical Resolution of Racemates by Formation of Diastereomeric Salts: Family Behaviour in Nucleation Inhibition

Dalmolen, Jan; Tiemersma‐Wegman, Theodora D.; Nieuwenhuijzen, José W.; Sluis, M. van der; Echten, Erik van; Vries, Ton R.; Kaptein, Bernard; Broxterman, Q. B.; Kellogg, Richard M.

doi:10.1002/chem.200500440

Cited by 38 publications

(31 citation statements)

References 16 publications

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“…From the molar ratio of resolving reagents in the first salts summarized in Table 2, all three resolving reagents had incorporated into the diastereomeric salts and the resolving reagent with a high yield in the parallel approach (also see Table 1) is easy to incorporate into the salts with a higher ratio. These results showed that the family resolution may not be suitable to the resolution of rac-1, although a cooperative effect was observed in the resolution with the mixtures of (2a+2f+2g) and (2a+2b+2g) [15,16].…”

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confidence: 61%

A parallel approach to direct resolution of albuterol

Zhong

Peng

et al. 2010

Chin. Sci. Bull.

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A library consisting of a series of O,O′-diaryzoyl-L-(-)-tartaric acids (2) was designed and synthesized. The substituent on the aromatic ring of 2 significantly affects the diastereomeric excess and efficiency of the resolution of racemic albuterol (1). Excellent resolving reagent 2a was selected for the resolution of rac-1 via the parallel approach. However, a family of three resolving reagents failed to improve the resolution efficiency of rac-1. resolution of albuterol, O,O′-diaryzoyltartaric acids, parallel resolution, family resolution Citation:Zhong Q L, Peng X H, Wu T F, et al. A parallel approach to direct resolution of albuterol.

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confidence: 61%

A parallel approach to direct resolution of albuterol

Zhong

Peng

et al. 2010

Chin. Sci. Bull.

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“…We note, for example, the profound nucleation inhibition effects observed in certain diastereomeric resolutions [34][35][36]. It is clear that there is still much to learn about the interface between crystallisation and nucleation.…”

Section: Nucleationmentioning

confidence: 96%

“…The result is increase of the solubility window from the area denoted with (a C b) to the larger area now (a C b C c) in which precipitation of pure diastereomer (p-salt in the illustration) may be expected. This is possible by the process of nucleation inhibition, a major effect now known to be behind the phenomenon known as Dutch Resolution [31][32][33][34][35][36].…”

Section: Dutch Resolutionmentioning

confidence: 99%

How to Use Pasteur’s Tweezers

Kellogg

2015

Advances in Organic Crystal Chemistry

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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 nonracemisable conglomerates.

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“…It exists as a nucleation inhibitor and extends the metastable zone for the more soluble diastereomer over the less soluble diastereomer. 3,4 The above mentioned separations follow the classical Pasteur method. The total amount of resolving agent mixture is in equivalent molar ratio to the racemate, and the diastereomeric salts are separated via fractional crystallization.…”

Section: Introductionmentioning

confidence: 99%

Application of mixtures of tartaric acid derivatives in resolution via supercritical fluid extraction

et al. 2007

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Racemic N-methylamphetamine (rac-MA) was resolved with 2R,3R-tartaric acid (TA) and its derivatives (O,O'-dibenzoyl-(2R,3R)-tartaric acid monohydrate (DBTA) and O,O'-di-p-toluoyl-(2R,3R)-tartaric acid (DPTTA)), individually and using them in different combinations. After partial diastereomeric salt formation, the free enantiomers were extracted by supercritical fluid extraction using carbon dioxide as solvent. DBTA and DPTTA are efficient resolving agents for rac-MA, the best chiral separation being obtained at a molar ratio of 0.25 resolving agent to racemic compound for both resolving agents (ee(E) = 82.5% and ee(E) = 57.9%, respectively). Compared with the two other acids, TA is practically unsuitable for enantiomer separation (ee(E) < 5%). Applying a mixture of one individually active and one ineffective acid in half the equivalent molar ratio, when the acids are in 1:1 ratio in the mixture, the resolution efficiency values obtained exceeded those obtained by using the components individually. Decreasing the molar ratio of resolving agent mixture to 0.25, at which the individual resolving agents give the best chiral separation, the obtained resolution efficiency values did not differ significantly from those expected. The outcome of the resolution process depended only on the amount of the individually active resolving agents in the mixture.

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The Dutch Resolution Variant of the Classical Resolution of Racemates by Formation of Diastereomeric Salts: Family Behaviour in Nucleation Inhibition

Cited by 38 publications

References 16 publications

A parallel approach to direct resolution of albuterol

A parallel approach to direct resolution of albuterol

How to Use Pasteur’s Tweezers

Application of mixtures of tartaric acid derivatives in resolution via supercritical fluid extraction

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