Continuous enantioselective crystallization of chiral compounds in coupled fluidized beds

Gänsch, Jonathan; Huskova, Nadiia; Kerst, Kristin; Temmel, Erik; Lorenz, Heike; Mangold, Michael; Janiga, Gábor; Seidel‐Morgenstern, Andreas

doi:10.1016/j.cej.2021.129627

Cited by 12 publications

(2 citation statements)

References 54 publications

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“…In recent years, numerous studies on improved variants of PC have been reported, mainly focused on delaying the nucleation of the nontarget enantiomer in two coupled crystallizers, − enabling continuous mode in coupled PC, , fluidized bed crystallization, , or coupling PC with selective dissolution …”

Section: Batchwise Pcmentioning

confidence: 99%

Shortcut Model for Batch Preferential Crystallization Coupled with Racemization for Conglomerate-Forming Chiral Systems

Bhandari

Carneiro

Lorenz

et al. 2022

Crystal Growth & Design

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Kinetically controlled preferential crystallization (PC) is a well-established elegant concept to separate mixtures of enantiomers of conglomerate-forming systems. Based on a smaller number of laboratory investigations, the key parameters of an available shortcut model (SCM) can be estimated, allowing for a rapid and reliable process design. This paper addresses a severe limitation of the method, namely, the limitation of the yield to 50%. In order to exploit the valuable counter enantiomer, the crystallization process is studied, coupled with a racemization reaction and a recycling step. It will be shown that the process integration can be performed in various ways. To quantify the different options in a unified manner and to provide a more general design concept, the SCM of PC is extended to include a kinetic model for the enzymatically catalyzed reaction. For illustration, model parameters are used, which characterize the resolution of the enantiomers of asparagine monohydrate and the racemization rate using an amino acid racemase. The theoretical study highlights the importance of exploiting the best stop time for batch operations in order to achieve the highest process productivity.

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Section: Batchwise Pcmentioning

confidence: 99%

Shortcut Model for Batch Preferential Crystallization Coupled with Racemization for Conglomerate-Forming Chiral Systems

Bhandari

Carneiro

Lorenz

et al. 2022

Crystal Growth & Design

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show abstract

“…Continuous production is projected to be adopted in the pharmaceutical industry, and the field of continuous synthesis of compounds has shown significant progress. − The continuous purification process represents a critical foundational technology for establishing fully continuous production. Resolution of chiral compounds is an essential technique for efficient separation and purification, and resolution by crystallization, a method applicable to compounds forming conglomerates, is a vital development subject due to its simplicity and scalability. − The preferential crystallization has been widely used as a classic resolution, − and its continuous operation has been thoroughly studied through various methods such as the mixed suspension mixed product removal method, , coupled preferential crystallization, − and fluidized bed crystallization. − However, when the products are racemates, the theoretical maximum yield of preferential crystallization is 50%. , …”

Section: Introductionmentioning

confidence: 99%

Semicontinuous Temperature Cycle-Induced Deracemization Using an Axially Chiral Naphthamide

Oketani,

Naito,

Hisaki

2024

Org. Process Res. Dev.

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This study outlines a practical, semicontinuous method for temperature cycle-induced deracemization (TCID) using a batch-mode crystallizer. We employed an axially chiral naphthamide derivative as a model compound and deracemized the crystalline phase by conventional TCID. To achieve continuity of deracemization, we harvested a part of the suspension after the conventional TCID, and then we fed a new racemic suspension into the enriched suspension and applied temperature cycles. By leaving a highly enriched crystalline phase as seed crystals to direct the chirality of the following enrichment, the enrichment process was significantly accelerated, verifying a stable and high production efficiency. Furthermore, from the perspective of process productivity, the moderate suspension density is optimal for efficient deracemization. In the naphthamide system, up to 7.71 g•L −1 • h −1 of productivity was achieved. Thanks to the simple operation, the method described here is applicable for most batch-mode deracemizations reported to date. In terms of industrial applications, semicontinuous deracemization could be a good option to utilize the existing batch-mode crystallizers.

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Optimization of a Continuous Fluidized Bed Process for the Separation of Enantiomers by Preferential Crystallization

Huskova

Mangold

Seidel‐Morgenstern

2021

31st European Symposium on Computer Aided Process Engineering

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Continuous enantioselective crystallization of chiral compounds in coupled fluidized beds

Cited by 12 publications

References 54 publications

Shortcut Model for Batch Preferential Crystallization Coupled with Racemization for Conglomerate-Forming Chiral Systems

Shortcut Model for Batch Preferential Crystallization Coupled with Racemization for Conglomerate-Forming Chiral Systems

Semicontinuous Temperature Cycle-Induced Deracemization Using an Axially Chiral Naphthamide

Optimization of a Continuous Fluidized Bed Process for the Separation of Enantiomers by Preferential Crystallization

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