Scalable and Sustainable Mechanochemical Deracemisation by Resonant Acoustic Mixing

Abstract

Resonant Acoustic Mixing (RAM) is introduced as a solvent-minimised, scalable approach to deracemisation, achieving enantiomeric excesses of up to 91%. The influence of processing parameters such as amount and nature of liquid additive on the deracemisation outcome were systematically investigated. RAM furthermore shows seamless 5-fold upscaling ability, facilitating near-gram-scale deracemisation with minimal solvent use (η = 0.02), enhanced reproducibility and reduced reaction times without the need for milling media. Notably, a racemic mixture was deracemised to 73% ee in 1.5 hours, showing enhanced efficiency compared to ball-milling and solvent-based deracemisation approaches. Mechanochemical deracemisation by RAM is a significant advancement, offering a faster, waste-minimising and scalable method, enabling a pathway to large-scale deracemisation processes while reducing waste.