Design of Crystallization Processes for the Resolution of Conglomerate-Forming Chiral Compounds Exhibiting Oiling Out
2012 (English)In: Organic Process Research & Development, ISSN 1083-6160, E-ISSN 1520-586X, Vol. 16, no 2, 294-310 p.Article in journal (Refereed) Published
A methodology for the design of cooling crystallization processes for chiral resolution from nonracemic initial solutions is presented. Such processes are encountered when chiral resolution is attained by hybrid processes, where the crystallization step is preceded by a pre-enrichment step accomplished by either asymmetric synthesis or another separation technique. The work focuses on substances that crystallize as conglomerates and accounts for the occurrence of oiling out, i.e., an undesired liquid liquid phase separation during crystallization. The generic ternary phase diagrams for conglomerate-forming systems with and without oiling out are derived. This knowledge is then applied to identify suitable operating conditions for chiral resolution. As crystallization is started from saturated solutions, the crystallization process is characterized by three parameters: the initial enantiomeric excess and the initial temperature, which together implicitly define the position of the operating point in the phase diagram, and the final operating temperature, which defines the composition and the amount of the phases present at the end of crystallization. For any initial enantiomeric excess, the methodology yields distinct areas in the initial versus final temperature plane containing pairs of operating temperatures that are suitable for chiral resolution. Such operating map bears great potential in improving the design and optimization of chiral resolution processes by crystallization.
Place, publisher, year, edition, pages
2012. Vol. 16, no 2, 294-310 p.
IdentifiersURN: urn:nbn:se:kth:diva-91267DOI: 10.1021/op200191dISI: 000300339700019ScopusID: 2-s2.0-84857510888OAI: oai:DiVA.org:kth-91267DiVA: diva2:509033
FunderEU, European Research Council, 214 129
QC 201203122012-03-122012-03-122012-03-12Bibliographically approved