(23f) Solid-State Deracemization of Conglomerate-Forming Chiral Compounds, Simple and Ubiquitous

Chiral compounds forming conglomerate crystals may experience solid-state deracemization, i.e., amplification of an initial enantiomeric excess in suspension up to homochirality, when in the presence of a racemization reaction in solution. There is a family of attractive paths to the manufacture through this route of enantiopure powders in the chemical and pharmaceutical industries, e.g., via Viedma ripening (an isothermal process, enhanced by crystal breakage and agglomeration) or via temperature cycles (with no obvious role of the other mechanisms). The same process has also been advocated to be a key component in the emergence of biological homochirality on Earth, hence closely linked to the origin and emergence of life. Different mechanisms and different mathematical models have been utilized to explain solid-state deracemization, though no consensus has been reached. In this work, through a simplified mathematical model (based on material balances and population balance equations) we demonstrate that there exists a simple necessary and sufficient condition for the attainment of solid-state deracemization via temperature cycles. Such condition is ubiquitous, thus making solid-state deracemization a common mechanism for the amplification of an enantiomeric asymmetry in conglomerate-forming chiral compounds. Using the model and through experiments with N-(2-methylbenzylidene)-phenylglycine amide (NMPA) we have demonstrated several features of the temperature cycles that induce solid-state deracemization, which allow arguing for the applicability of the same criterion to isothermal Viedma ripening and for their relevance to early Earth processes related to the origin of biological homochirality.