(391m) Purification of 2-Amino-1-Phenylethanol Enantiomers By Stripping Crystallization

Stripping crystallization (SC) is a new separation technique which combines distillation and crystallization. Basically, SC is operated at a triple-point condition, in which the liquid is simultaneously vaporized and crystallized due to the three-phase equilibrium. In essence, the process is continued until the liquid phase is completely eliminated and only the pure solid crystals remain in the feed. Thus, crystal washing is not required since only pure solid crystals remain in the feed and no impurities are adhered on the crystal surfaces at the end of SC. In the previous research, SC has been successfully applied to separate p-xylene from the mixed xylenes by Shiau et al. [Shiau et al., 2005; 2006; 2008].

    2-Amino-1-phenylethanol (2-APE) is an important basic skeleton in many adrenergic drugs and is often used as ingredients of cold medicines and anorectics. As the biological activity and pharmacokinetics of the enantiomers of a chiral drug can be different, the objective of this research is to apply SC to purify R-2-APE from the chiral 2-APE mixture. The results can provide important information in the pharmaceutical industry. A thermodynamic model is developed to simulate the three-phase equilibrium during the SC operation and to direct the batch SC experiments. The experiments show that no crystallization occurs during SC without seeding due to subcooling of the liquid enantiomers. On the other hand, seeding can eliminate subcooling during SC, leading to the R-2-APE crystals gradually formed preferentially on the seeds. Thus, seeding with magnetic stirring can be successfully employed to purify R-2-APE from the 2-APE enantiomers. The experimental purity of the resulting R-2-APE product is higher than predicted by the model although the experimental recovery ratio is slightly lower than the simulated recovery ratio.

References:

1.  Shiau, L. D., Wen, C. C. and Lin, B. S. Separation and purification of p-xylene from the mixture of m-xylene and p-xylene by distillative freezing, Ind. Eng. Chem. Res, 44(7), 2258-2265, 2005.

2.  Shiau, L. D., Wen, C. C. and Lin, B. S. Application of distillative freezing in the separation of o-xylene and p-xylene, A.I.Ch.E. Journal, 52(5), 1962-1967, 2006. 

3.  Shiau, L. D., Wen, C. C. and Lin, B. S. Separation of p-xylene from the multicomponent xylene system by stripping crystallization, A.I.Ch.E. Journal, 54(1), 337-342, 2008.