Design of Crystallization Processes for the Resolution of Conglomerate-Forming Chiral Compounds Exhibiting Oiling Out (original) (raw)
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Conglomerate crystallisation is the behaviour responsible for spontaneous resolution and the discovery of molecular chirality by Pasteur. The phenomenon of conglomerate crystallisation of chiral organic molecules has been left largely undocumented and offers synthetic chemists a potential new chiral pool not reliant on biological systems to supply stereochemical information. While other crystallographic behaviours can be interrogated by automated searching, conglomerate crystallisations are not identified within the Cambridge Structural Database (CSD) and are therefore not accessible by conventional means. By conducting a manual search of the CSD, a list of over 1,700 chiral species capable of conglomerate crystallisation was curated by inspection of the synthetic routes described in each publication. The majority of these are produced by synthetic chemists who seldom note and rarely exploit the implications this phenomenon can have on the enantioenrichment of their crystalline mate...
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The purpose of this paper is to investigate the concept of preferential crystallization, with a focus on aspects of quantification and application from an engineering point of view. The amino acid threonine was used as a model system in the experiments performed. Application of on-line polarimetry in combination with measurements of an on-line density meter proved the general applicability of this method in order to monitor directly the resolution progress, to recognize the region of “safe” resolution, and to gain information about the crystallization kinetics. For evaluation of the crystal growth kinetics of the desired enantiomers, the method of moments was applied to analyze isothermal single-step crystallization experiments. A population balance model is used in order to simulate the time changes of liquid-phase composition during the preferential crystallization process. Finally, preliminary experimental results regarding the cyclic operation mode are presented. Chirality 17:S183–S195, 2005. © 2005 Wiley-Liss, Inc.