Temperature cycle induced deracemization

Intaraboonrod, Kritsada; Lerdwiriyanupap, Tharit; Hoquante, Marine; Coquerel, Gérard; Flood, Adrian E.

doi:10.1016/j.mencom.2020.07.002

Cited by 24 publications

(30 citation statements)

References 56 publications

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“…This information is crucial when studying, for example, the deracemization of conglomerates by preferential crystallization 84 or attrition methods such as Viedma ripening 85 or Temperature Cycling Induced Deracemization. 86 Since these crystallization techniques rely, at least partially, on secondary nucleation and Ostwald ripening, it is the number of crystals of a given configuration that is of interest, not the overall molecular proportions.…”

Section: Crystal Assembliesmentioning

confidence: 99%

Chirality determination in crystals

2021

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This tutorial review article discusses chirality determination in the solid state, both in single crystals and in crystal assemblies, with an emphasis on X-ray diffraction. The main principles of using X-ray diffraction to reliably determine absolute structure are summarized, and the complexity which can be encountered in chiral structures-kryptoracemates, scalemates, and inversion twinning-is illustrated with examples from our laboratories and the literature. We then address the problem of the bulk crystallization and discuss different techniques to determine chirality in a large assembly of crystal structures, with a special prominence given to an X-ray natural circular dichroism mapping technique that we recently reported.

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Section: Crystal Assembliesmentioning

confidence: 99%

Chirality determination in crystals

2021

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“…Under those circumstances, any energy flux passing through the suspension for long enough will lead to the disappearance of one population of homochiral crystals. A constant mechanical stress such as grinding (known as Viedma ripening) [22], numerous temperature cycles [23], long exposure to ultrasound [24], pressure stress [25] or microwaves [26] are general methods enabling the evolution of the initial dual population of particles to a single population of crystals containing a single enantiomer only, i.e., deracemization. Those methods operate rather close to thermodynamic equilibrium.…”

Section: Deracemization Induced By a Flux Of Energy Crossing The Susp...mentioning

confidence: 99%

“…Symmetry 2020, 12, x FOR PEER REVIEW 5 of 18 Repetitive oscillations of temperature are also able to induce deracemization in the system without limiting scale. This spontaneous process is known as Temperature Cycle-Induced Deracemization (known as TCID) [23]. The temperature gradient could be in space [30] or in time [31], or even both [32].…”

Section: Deracemization Induced By a Flux Of Energy Crossing The Susp...mentioning

confidence: 99%

Spontaneous and Controlled Macroscopic Chiral Symmetry Breaking by Means of Crystallization

Coquerel

Hoquante

2020

Symmetry

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In this paper, macroscopic chiral symmetry breaking refers to as the process in which a mixture of enantiomers departs from 50–50 symmetry to favor one chirality, resulting in either a scalemic mixture or a pure enantiomer. In this domain, crystallization offers various possibilities, from the classical Viedma ripening or Temperature Cycle-Induced Deracemization to the famous Kondepudi experiment and then to so-called Preferential Enrichment. These processes, together with some variants, will be depicted in terms of thermodynamic pathways, departure from equilibrium and operating conditions. Influential parameters on the final state will be reviewed as well as the impact of kinetics of the R ⇔ S equilibrium in solution on chiral symmetry breaking. How one can control the outcome of symmetry breaking is examined. Several open questions are detailed and different interpretations are discussed.

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“…The batch implementation of such a process is defined as attrition-enhanced deracemization if particles’ dissolution and growth are induced by grinding the solids to form small fragments that can easily dissolve 7 , 8 , 10 or deracemization via temperature cycles if the suspension undergoes periodic temperature variations. 6 , 11 The latter method has been widely studied in the past years because of its easy implementation in a thermostated stirred tank reactor and the availability of numerous operating parameters, which can be adjusted to achieve the target specifications. Different works focused on the effect of such operating conditions on the process performance in order to master the design of highly productive operations.…”

Section: Introductionmentioning

confidence: 99%

“…This feature is particularly relevant for pharmaceutical applications, which require isolating the pure target enantiomer (eutomer) to avoid the effects caused by the undesired species (distomer). , To address this challenging separation task, several processes have been developed . Among them, crystallization-based methods, such as preferential crystallization and solid-state deracemization, − are preferred since they enable to collect a highly pure product in its solid form. Particularly, deracemization processes have the advantage of transforming the undesired enantiomer of a racemizable conglomerate-forming compound into the desired one, thus increasing the process yield.…”

Section: Introductionmentioning

confidence: 99%

Deracemization via Periodic and Non-periodic Temperature Cycles: Rationalization and Experimental Validation of a Simplified Process Design Approach

Breveglieri

Bodák

Mazzotti

2021

Org. Process Res. Dev.

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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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Temperature cycle induced deracemization

Cited by 24 publications

References 56 publications

Chirality determination in crystals

Chirality determination in crystals

Spontaneous and Controlled Macroscopic Chiral Symmetry Breaking by Means of Crystallization

Deracemization via Periodic and Non-periodic Temperature Cycles: Rationalization and Experimental Validation of a Simplified Process Design Approach

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