Poster De Conférence Année : 2025

Mechanochemical racemization : key parameters for a reproducible method

Résumé

During the last decades, separation of enantiomers has become of paramount importance since more than 50% of the marketed drugs are chiral. Several methods have been developed to isolate pure enantiomers, aiming at the highest yield, productivity and lowest cost. Some of them rely on simple enantiomeric separation but result in a waste of 50% since the counter enantiomer is considered an impurity. To increase the yield and make these methods more attractive, the opposite handedness can be racemized in solution and separated again. However, the use of solvent presents an important drawback: in addition to potential toxicity, the solvent needs to be recycled, increasing the cost and the carbon footprint of the process. Besides, mechanochemistry refers to the use of high energy milling to overcome the energy barrier required for several chemical reactions. A mechanochemical process requires only a small amount of solvent, while maintaining a similar (or even better) yield of reaction compared to solutions. Thus, we managed to transfer racemization to high energy milling conditions, improving process productivity, and providing a greener approach to enantioconversion. Even if we proved the possibility to perform such reactions using high energy milling, we also demonstrated a potential lack of reproducibility in this approach. After discovering the emergence of a "snow-ball" effect but also studying the impact of water contamination on the racemization rate, we managed to find a set of parameters that sufficiently reduced both effects. Nevertheless, making the process more reproducible affects its kinetics, introducing a compromise between efficiency and reproducibility.

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Dates et versions

hal-05084985 , version 1 (26-05-2025)

Identifiants

  • HAL Id : hal-05084985 , version 1

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Chrystal Lopes, Clément Brandel, Tom Leyssens, Yohann Cartigny. Mechanochemical racemization : key parameters for a reproducible method. Cristal 11, May 2025, Marseille, France. ⟨hal-05084985⟩
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