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Mechanochemical Deracemization: A Sustainable Approach to Enantiopurity

2025/01/03 by Job Gieling, Guillaume Wéry, Chrystal Lopes +5 · 1 voice
Chemistry · Physics and Astronomy · Biochemistry, Genetics and Molecular Biology · #Crystallography and molecular interactions #Origins and Evolution of Life #Protein Structure and Dynamics

paper · doi:10.1002/chem.202404120

openalex publication_date 2025/01/03 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/02

Abstract

We introduce mechanochemical deracemization (MCDR) as a novel strategy for obtaining enantiopure compounds. This study demonstrates the successful transposition of six archetypical deracemization reactions from a solvent-based to a solvent-minimized ball milling environment. The scope includes a ketone, isoindolinones, imines, an ester, and an inorganic compound, all of which deracemized successfully. Key parameters such as milling material, ball number and size, the use of a bulk material and liquid-assisted grinding (LAG) were systematically investigated, revealing their crucial role. Quantitative enantiomeric excesses (ee) were achieved, while reaction times were reduced by up to 97 % and solvent consumption by as much as 100 %. This work establishes MCDR as a versatile, sustainable pathway to enantiopure compounds. By highlighting the generalizability of this approach and its huge potential for minimizing waste, this study provides the foundation for future advancements in mechanochemical deracemization.

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