Complete chiral resolution in a continuous flow crystallizer with recycle stream

Peter Neugebauer*, Andrea Triebl, Heidrun Gruber-Woelfler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Repeated temperature cycling of crystals from a conglomerate forming chiral substance suspended in their saturated solution has shown to be effective in converting a mixture of both enantiomers into an enantiomerically pure state. While by now a large number of different setups has been demonstrated, here we show for the first time how a continuous flow temperature cycler with recycle stream is capable of establishing enantiopurity while converting a racemic starting suspension. By capturing the most significant parameters influencing the process kinetics a competitive productivity could be achieved. We show, that fast crystal dissolution at high undersaturations and fast crystal growth at high supersaturations are speeding up the process as long as nucleation can be kept to a minimum or avoided at all. Temperature cycling has shown to result in a shift towards larger sizes for the particle size distribution of the crystals suspended, which is detrimental to the present process governed by size-dependent solubility. By implementing an ultrasound unit recycled material was comminuted, resulting in nearly stable deracemization rates. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)483-493
Number of pages11
JournalJournal of Flow Chemistry
Issue number3
Publication statusPublished - Sept 2021


  • Chiral resolution
  • Deracemization
  • Temperature cycling
  • Tubular crystallizer

ASJC Scopus subject areas

  • Chemistry (miscellaneous)
  • Fluid Flow and Transfer Processes
  • Organic Chemistry


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