Scaling up temperature cycling-induced deracemization by suppressing nonstereoselective processes

René R. E. Steendam, Joop H. ter Horst

Research output: Contribution to journalArticle

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Abstract

The scale-up of Temperature Cycling-Induced Deracemization (TCID) of sodium bromate is feasible provided that two nonstereoselective processes are suppressed. Both nonstereoselective processes occur as a result of insufficient crystal breakage or attrition. In the absence of crystal breakage or attrition during the temperature cycles, large crystals emerge and the resulting small total crystal surface area is unable to sufficiently consume the supersaturation during cooling, resulting in nonstereoselective nucleation. This nonstereoselective process can be avoided by applying small temperature cycles involving small dissolving solid fractions. However, this leads to a slow deracemization rate. In addition, crystals undergo nonstereoselective agglomeration, which leads to the formation of large racemic agglomerates constructed of both chiral forms. To counteract their formation, secondary nucleation through crystal breakage was found to be a key requirement. At a large scale, a homogenizer was used to induce crystal breakage which, in combination with temperature cycles, led to the removal of racemic agglomerates as well as a significant increase in the deracemization rate. Overusing the homogenizer, however, caused the enantiomeric excess increase to stop. Our experiments show the importance of secondary nucleation in TCID of sodium bromate. However, secondary nucleation is currently not incorporated in the TCID process models. In the presence of a large amount of crystals which facilitates a sufficiently large crystal surface area at the highest temperature and careful use of the homogenizer, TCID leads to complete deracemization in volumes up to 1 L, demonstrating the potential to extend TCID to industrial applications.

LanguageEnglish
Pages3008-3015
Number of pages8
JournalCrystal Growth and Design
Volume18
Issue number5
Early online date28 Mar 2018
DOIs
StatePublished - 2 May 2018

Fingerprint

scaling
Crystals
cycles
Temperature
crystals
nucleation
Nucleation
bromates
comminution
temperature
crystal surfaces
sodium
Sodium
supersaturation
agglomeration
Supersaturation
dissolving
Industrial applications
Agglomeration
cooling

Keywords

  • temperature cycling-induced deracemization
  • TCID
  • sodium bromate
  • crystal breakage
  • nonstereoselective process

Cite this

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title = "Scaling up temperature cycling-induced deracemization by suppressing nonstereoselective processes",
abstract = "The scale-up of Temperature Cycling-Induced Deracemization (TCID) of sodium bromate is feasible provided that two nonstereoselective processes are suppressed. Both nonstereoselective processes occur as a result of insufficient crystal breakage or attrition. In the absence of crystal breakage or attrition during the temperature cycles, large crystals emerge and the resulting small total crystal surface area is unable to sufficiently consume the supersaturation during cooling, resulting in nonstereoselective nucleation. This nonstereoselective process can be avoided by applying small temperature cycles involving small dissolving solid fractions. However, this leads to a slow deracemization rate. In addition, crystals undergo nonstereoselective agglomeration, which leads to the formation of large racemic agglomerates constructed of both chiral forms. To counteract their formation, secondary nucleation through crystal breakage was found to be a key requirement. At a large scale, a homogenizer was used to induce crystal breakage which, in combination with temperature cycles, led to the removal of racemic agglomerates as well as a significant increase in the deracemization rate. Overusing the homogenizer, however, caused the enantiomeric excess increase to stop. Our experiments show the importance of secondary nucleation in TCID of sodium bromate. However, secondary nucleation is currently not incorporated in the TCID process models. In the presence of a large amount of crystals which facilitates a sufficiently large crystal surface area at the highest temperature and careful use of the homogenizer, TCID leads to complete deracemization in volumes up to 1 L, demonstrating the potential to extend TCID to industrial applications.",
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Scaling up temperature cycling-induced deracemization by suppressing nonstereoselective processes. / Steendam, René R. E.; ter Horst, Joop H.

In: Crystal Growth and Design, Vol. 18, No. 5, 02.05.2018, p. 3008-3015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Scaling up temperature cycling-induced deracemization by suppressing nonstereoselective processes

AU - Steendam,René R. E.

AU - ter Horst,Joop H.

N1 - This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crustal Growth and Design, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see hrrps://doi.org/10.1021/acs.cgd.8b00121.

PY - 2018/5/2

Y1 - 2018/5/2

N2 - The scale-up of Temperature Cycling-Induced Deracemization (TCID) of sodium bromate is feasible provided that two nonstereoselective processes are suppressed. Both nonstereoselective processes occur as a result of insufficient crystal breakage or attrition. In the absence of crystal breakage or attrition during the temperature cycles, large crystals emerge and the resulting small total crystal surface area is unable to sufficiently consume the supersaturation during cooling, resulting in nonstereoselective nucleation. This nonstereoselective process can be avoided by applying small temperature cycles involving small dissolving solid fractions. However, this leads to a slow deracemization rate. In addition, crystals undergo nonstereoselective agglomeration, which leads to the formation of large racemic agglomerates constructed of both chiral forms. To counteract their formation, secondary nucleation through crystal breakage was found to be a key requirement. At a large scale, a homogenizer was used to induce crystal breakage which, in combination with temperature cycles, led to the removal of racemic agglomerates as well as a significant increase in the deracemization rate. Overusing the homogenizer, however, caused the enantiomeric excess increase to stop. Our experiments show the importance of secondary nucleation in TCID of sodium bromate. However, secondary nucleation is currently not incorporated in the TCID process models. In the presence of a large amount of crystals which facilitates a sufficiently large crystal surface area at the highest temperature and careful use of the homogenizer, TCID leads to complete deracemization in volumes up to 1 L, demonstrating the potential to extend TCID to industrial applications.

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