Mechanistic Insights into Growth-Dominated Chiral Amplification: Kinetic Control and Thermodynamic Constraints in Evaporative Crystallization

Deracemization via crystallization traditionally requires alternating dissolution–growth cycles. Although crystal growth has conventionally been regarded as a source of enantiomeric erosion, the emerging “growth-dominated” mechanism fundamentally challenges this view. This study provides the first systematic validation of this novel mechanism in evaporative crystallization. Using N-(2-methylbenzylidene)-phenylglycine amide (NMPA) as a model conglomerate, we reveal that amplification efficiency relies on a delicate interplay between kinetic control and thermodynamic constraints. Kinetically, the evaporation rate is the paramount determinant, as rapid evaporation generates high supersaturation, driving the system far from equilibrium to efficiently couple asymmetric crystal growth with racemization. Thermodynamically, the amplification potential is governed by the proportion of the newly grown material relative to the seeds, necessitating high temperatures and low solid loadings for optimal enantioenrichment. Additionally, the enantiopurity baseline, the competitive growth of the minor enantiomer, and mass transport limitations impose strict boundary conditions on the amplification performance. These findings extend the growth-dominated amplification mechanism to a practical evaporative crystallization environment and provide fundamental insights into the governing principles of asymmetric crystallization.