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Communication Dans Un Congrès Année : 2024

Combining enantio-purification with mechanochemistry

Résumé

: In the pharmaceutical field, more than 50% of the commercialized organic molecules are chiral. 1 The corresponding enantiomers can have different biological and chemical properties in contact of a living organism due to their respective chirality. As the counter enantiomer can exhibit a potential toxicity, an enantiopure drug is preferred and required the use of a separation process. Many methods to access an enantiopure molecule have been developed. Among them, chiral HPLC or asymmetric organic synthesis are available, but crystallization processes are generally preferred due to their low cost. Among enantio-purification methods, the deracemization process combines enantioconversion (via a racemization thanks to the use of a racemizing agent) and crystals dissolution/crystallization.2 Despite its capacity to reach high enantiomeric excess (theoretically 100%), this process has some drawbacks : (i) the take-off time of the classical deracemization processes in solution reaches hours and even days and (ii) the racemization reaction (in solution) requires solvent that can be toxic and has to be treated. During the last decades, interest in mechanochemistry has significantly increased. Mechanochemical reactions are described as reactions induced by a mechanical impact by using no (or a minimum amount of) solvent. The present project has for objective to tackle deracemization issues by associating this process to mechanochemistry (Figure 1a). The model compound used for this proof of concept is the 1-(4-chlorophenyl)-4,4-dimethyl-2-(1,2,4-triazol-1-yl)pentan-3-one, (Cl-TAK, Fig. 1b). Results of this study demonstrate that this combination give access to enantiopure solid with a takeoff time of the process that is significantly reduced comparing to a classical deracemization.
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Dates et versions

hal-04619800 , version 1 (21-06-2024)

Identifiants

  • HAL Id : hal-04619800 , version 1

Citer

Chrystal Lopes, Clément Brandel, Valérie Dupray, Oleksii Shemchuk, Tom Leyssens, et al.. Combining enantio-purification with mechanochemistry. JNOEJC 24, Jun 2024, Mont-Saint-Aignan, France. ⟨hal-04619800⟩
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