On the Effect of Secondary Nucleation on Deracemization through Temperature Cycles. Issue 6 (22nd January 2020)

• Record Type: Journal Article
• Authors: Cameli, Fabio; ter Horst, Joop H.; Steendam, René R. E.; Xiouras, Christos; Stefanidis, Georgios D.
• Is Part Of: Chemistry. Volume 26:Issue 6(2020)
• Page Start: 1344
• Page End: 1354
• Publication Date: 2020-01-22
• Subjects: chiral resolution -- crystal engineering -- crystal growth -- microwave chemistry -- secondary nucleation; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201904239
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Herein, the pivotal role of secondary nucleation in a crystallization‐enhanced deracemization process is reported. During this process, complete and rapid deracemization of chiral conglomerate crystals of an isoindolinone is attained through fast microwave‐assisted temperature cycling. A parametric study of the main factors that affect the occurrence of secondary nucleation in this process, namely agitation rate, suspension density, and solute supersaturation, confirms that an enhanced stereoselective secondary nucleation rate maximizes the deracemization rate. Analysis of the system during a single temperature cycle showed that, although stereoselective particle production during the crystallization stage leads to enantiomeric enrichment, undesired kinetic dissolution of smaller particles of the preferred enantiomer occurs during the dissolution step. Therefore, secondary nucleation is crucial for the enhancement of deracemization through temperature cycles and as such should be considered in further design and optimization of this process, as well as in other temperature cycling processes commonly applied in particle engineering. Abstract : Enhanced deracemization : Crystallization‐enhanced rapid and complete deracemization of a chiral isoindolinone was achieved by fast microwave‐assisted temperature cycling. The crucial role of stereoselective secondary nucleation in this process was elucidated in a targeted parametric study, which showed that optimization of this phenomenon leads to maximization of the deracemization rate (see figure).