The Role of Nucleation Inhibition in Optical Resolutions with Families of Resolving Agents

Nieuwenhuijzen, José W.; Grimbergen, R. F. P.; Koopman, Corine; Kellogg, Richard M.; Vries, Ton R.; Pouwer, Kees; Echten, Erik van; Kaptein, Bernard; Hulshof, L.A.; Broxterman, Q. B.

doi:10.1002/1521-3773(20021115)41:22<4281::aid-anie4281>3.0.co;2-f

Cited by 62 publications

(12 citation statements)

References 2 publications

(3 reference statements)

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“…Inhibitor acts by widening the width of the metastable zone of supersaturation (the temperature of the zone between dissolution and the lower temperature at which precipitation begins) to a greater extent for the more soluble salt than the less soluble salt. 36,37 Therefore, to increase the optical purity of the less soluble salt, Dutch resolution of rac-1 was carried out with (R)-4 or (S)-4 as additive. 0.9 equimolar resolving agent and 0.1 equimolar (R)-4 or (S)-4 were used with rac-1 (186 mg, 1 mmol), the resolution solvent was isopropanol, and the volume was 1 ml.…”

Section: Dutch Resolution Of Rac-1 With Resolving Agentsmentioning

confidence: 99%

Diastereomeric Resolution of Racemic o‐Chloromandelic Acid

et al. 2012

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The separation of rac-o-chloromandelic acid 1 with enantiopure aryloxypropylamine via diastereomeric salt formation was investigated. (R)-o-chloromandelic acid (R)-1, a key intermediate for the antithrombotic agent clopidogrel, was obtained in 65% yield and 98% ee by Dutch resolution of rac-1 with (S)-2-hydroxyl-3-(p-chlorophenoxy) propylamine (S)-5 as resolving agent and (S)-2-hydroxyl-3-(o-nitrophenoxy) propylamine (S)-4 as nucleation inhibitor.

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Section: Dutch Resolution Of Rac-1 With Resolving Agentsmentioning

confidence: 99%

Diastereomeric Resolution of Racemic o‐Chloromandelic Acid

et al. 2012

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“…55,56 The use of family of resolving agents for the racemate resolution effectively changes trial-anderror resolution method into an acceptable and almost routine practice. [55][56][57][58][59][60][61][62][63][64][65][66] The extremely high success rate, defined in terms of yield and enantiomeric excess in a first trial, is the most attractive feature of this method. Out of the 1000 tested racemate resolutions, 95% have been reported as successful.…”

Section: Introductionmentioning

confidence: 99%

“…Family resolution approach called Dutch Resolution was discovered by Ton Vries and reported in a seminal paper in 1998 . The use of family of resolving agents for the racemate resolution effectively changes trial‐and‐error resolution method into an acceptable and almost routine practice . The extremely high success rate, defined in terms of yield and enantiomeric excess in a first trial, is the most attractive feature of this method.…”

Section: Introductionmentioning

confidence: 99%

Dutch Resolution of a configurationally stable [5]helquat

et al. 2018

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Synthesis and nontrivial optical resolution of a helicene-like dication, helquat 1, has been accomplished. Starting with gram scale of the racemic helquat 1 sample, Dutch Resolution using family of 3 tartrate anions was key to achieve successful separation of M and P helical enantiomers of 1. Hundreds of milligrams of each enantiomer of this configurationally stable C -symmetric helquat have been obtained. Racemization barrier of 1 has been determined. To our knowledge this is the first report on Dutch Resolution performed with a helicene-like compound. Moreover, there are no literature precedents for Dutch Resolution of chiral quaternary ammonium cations.

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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 Role of Nucleation Inhibition in Optical Resolutions with Families of Resolving Agents

Cited by 62 publications

References 2 publications

Diastereomeric Resolution of Racemic o‐Chloromandelic Acid

Diastereomeric Resolution of Racemic o‐Chloromandelic Acid

Dutch Resolution of a configurationally stable [5]helquat

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

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