Deracemization via Periodic and Non-periodic Temperature Cycles: Rationalization and Experimental Validation of a Simplified Process Design Approach
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Date
2021-11-19
Publication Type
Review Article
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yes
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Abstract
Solid-state deracemization via temperature cycles is a promising technique that combines crystallization and racemization in the same batch process to attain enantiomer purification. This method is particularly attractive because the target enantiomer can be isolated with a 100% yield, and a large number of operating parameters can be adjusted to do this effectively. However, this implies that several choices need to be made to design the process for a new compound. In this work, we provide a solution to this dilemma by suggesting a simplified model-free design approach based on a single dimensionless parameter, that is, the dissolution factor, that represents the cycle capacity. This quantity is obtained from a novel rescaling of the model equations proposed in previous work and acts as a handy design parameter because it only depends on the operating conditions, such as the suspension density, the enantiomeric excess, and the difference in solubility between high and low temperatures in the cycle. With extensive modeling studies, supported by experimental results, we demonstrate the primary and general effect of the dissolution factor on the deracemization process and thus its relevance for the process design. Through both experiments and simulations, we rationalize and evaluate the process performance when periodic and non-periodic temperature cycles are applied to the deracemization of virtual and real compounds with different properties, that is, growth rate and solubility. Based on the approach proposed here, we clarify how the combined effect of more operating conditions can be exploited to obtain quasi-optimal process performance, which results superior when deracemization via periodic temperature cycles is performed.
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published
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Journal / series
Volume
25 (11)
Pages / Article No.
2551 - 2565
Publisher
American Chemical Society
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Subject
Deracemization; temperature cycles; process design; effect of kinetics; compound-specific behavior
Organisational unit
03484 - Mazzotti, Marco (emeritus) / Mazzotti, Marco (emeritus)
Notes
Funding
722456 - Continuous Resolution and Deracemization of Chiral Compounds by Crystallization (EC)
788607 - Studying Secondary Nucleation for the Intensification of Continuous Crystallization (EC)
788607 - Studying Secondary Nucleation for the Intensification of Continuous Crystallization (EC)