On the effect of secondary nucleation on deracemization through temperature cycles

Fabio Cameli, Joop H. ter Horst, René R. E. Steendam, Christos Xiouras, Georgios D. Stefanidis

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)1344-1354
Number of pages11
JournalChemistry - A European Journal
Issue number6
Early online date20 Nov 2019
Publication statusPublished - 27 Jan 2020


  • chiral resolution
  • crystal engineering
  • crystal growth
  • microwave chemistry
  • secondary nucleation


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