Synthesis of Chromatography−Crystallization Hybrid Separation Processes

Fung, Ka Yip; Ng, Ka Ming; Wibowo, Christianto

doi:10.1021/ie0496075

Cited by 23 publications

(26 citation statements)

References 14 publications

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“…In most cases it requires an enriched solution with a molar excess of the desired enantiomer, which makes coupling it with chromatography a very attractive alternative. The design and optimization of the hybrid chromatography-crystallization process is discussed in Fung and Ng (2005), Ströhlein et al (2003), and Amanullah and Mazzoti (2006). The feasibility of crystallization as the predominant or the auxiliary process depends on the shape of the ternary phase diagram of the enantiomers in a suitable solvent.…”

Section: Enantioseparation Via Chromatography and Crystallizationmentioning

confidence: 99%

Ternary phase diagram of ketamine ((R,S)-2-(2-chlorophenyl)-2methylaminocyclohexanone) in ethanol and preliminary studies aiming at Enantioselective Crystallization of S-ketamine

Barros

Tamagawa

Santana

et al. 2009

Braz. J. Chem. Eng.

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-Crystallization is an important industrial-scale process for the purification of enantiomers that depends on a phase diagram. In this work, the ternary phase diagram of R-and S-ketamine in ethanol was determined. The eutectic point indicated that crystallization of pure enantiomers from solutions containing more than 75% of the desired enantiomer is feasible. Solubility studies showed the feasibility of using temperature control to conduct the process. Batch crystallization of ketamine (S/R:80/20) solutions at 25°C provided the isolation of S-ketamine (purity of 100%) with a yield from 65 to 70% and a productivity of 6.5 g/(l h).

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Section: Enantioseparation Via Chromatography and Crystallizationmentioning

confidence: 99%

Ternary phase diagram of ketamine ((R,S)-2-(2-chlorophenyl)-2methylaminocyclohexanone) in ethanol and preliminary studies aiming at Enantioselective Crystallization of S-ketamine

Barros

Tamagawa

Santana

et al. 2009

Braz. J. Chem. Eng.

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“…On the other hand, crystallization is appropriate for the isolation of a product with high purity from a multicomponent mixture, but separation effect and yield are strongly affected by the presence of other impurity compounds, especially those possessing similar molecular structures as the crystallizing product. Therefore, the hybrid between chromatography and crystallization can have a synergistic effect, which can be developed as a robust and efficient separation approach for the isolation of bioactive compounds from complex multicomponent mixtures [8]. It has been reported that a hybrid chromatography-crystallization separation process resulted in improved purification efficiency for the separation of a racemic mixture [9].…”

Section: Introductionmentioning

confidence: 99%

Chromatography‐Crystallization Hybrid Process for Artemisinin Purification from Artemisia annua

Christensen

Fretté

et al. 2010

Chem Eng & Technol

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The feasibility of using a chromatography-crystallization hybrid separation process for isolation and purification of artemisinin from the herbal plant Artemisia annua was studied. After separating the crude extracts of Artemisia annua by flash column chromatography, a two-step antisolvent crystallization process was used for further isolation and purification. The two-step antisolvent crystallization process was designed based on the solubility of artemisinin in different solvents and solvent mixtures. The first step crystallization process was to remove impurities from the solution and the second step to isolate artemisinin. The crystallization behavior of the two polymorphs of artemisinin during the antisolvent crystallization process was also studied by performing crystallization in solutions of artemisinin in acetonitrile and acetone, respectively. It was observed that the formation of the two polymorphs of artemisinin in acetone solution follows the Ostwald's rule of stages. Fast feeding of the antisolvent (water) resulted in crystallization of the metastable triclinic form which then transformed to the stable orthorhombic form through a solvent-mediated transformation mechanism. The stable orthorhombic form crystallized out when water was fed slowly. Crystallization from acetonitrile always yielded the stable orthorhombic form regardless of the feeding rate of the antisolvent. Finally, a chromatography-crystallization hybrid separation process was proposed and tested. The results of the present work demonstrated the feasibility of combining the advantages of column chromatography and crystallization to improve efficiency of the isolation of artemisinin from Artemisia annua.

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“…[9][10][11][12] Using a preliminary chromatographic step to achieve an enantiomeric enrichment exceeding the eutectic composition in the chiral system, sets the threshold for a subsequent enantioselective crystallization process. This approach has proved to be an adequate alternative to a single chromatographic separation.…”

Section: Introductionmentioning

confidence: 99%

Application of preferential crystallization to resolve racemic compounds in a hybrid process

2006

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The application of preferential crystallization is at present limited to conglomerate forming systems, which cover only a minor part of chiral substances. In this paper, a hybrid process is proposed that extends the applicability of the preferential crystallization principle to the more common racemic compound forming systems. It comprises a preliminary (e.g., chromatographic) enantiomeric enrichment step and preferential crystallization to finally produce the desired pure enantiomer(s). The applicability of preferential crystallization to racemic compounds is demonstrated on the example of mandelic acid as a model system. Direct monitoring of the separation progress is performed using combined online polarimetry and online density measurements. A cyclic crystallization process, which provides alternating the pure mandelic acid enantiomer and the racemic compound, is feasible and allows the resolution of rac-mandelic acid as part of the proposed hybrid approach.

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Synthesis of Chromatography−Crystallization Hybrid Separation Processes

Cited by 23 publications

References 14 publications

Ternary phase diagram of ketamine ((R,S)-2-(2-chlorophenyl)-2methylaminocyclohexanone) in ethanol and preliminary studies aiming at Enantioselective Crystallization of S-ketamine

Ternary phase diagram of ketamine ((R,S)-2-(2-chlorophenyl)-2methylaminocyclohexanone) in ethanol and preliminary studies aiming at Enantioselective Crystallization of S-ketamine

Chromatography‐Crystallization Hybrid Process for Artemisinin Purification from Artemisia annua

Application of preferential crystallization to resolve racemic compounds in a hybrid process

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