Abstract

Conglomerate crystallization, also known as spontaneous resolution, occurs when molecules crystallize in a non-centrosymmetric space group. Both racemic and achiral building blocks can crystalize as conglomerates to form chiral crystals. The chiral outcome (i.e. the distribution of left- versus right-handed crystals) can be stochastic or non-stochastic depending on the environment and crystallization conditions. Herein the influence of primary and secondary nucleation in the conglomerate crystallization of benzil was explored. The results indicate that chiral amplification is favored under conditions that promote secondary nucleation. The complete and controlled chiral amplification of benzil was confirmed via attrition-enhanced deracemization (i.e. Viedma ripening) in under 2 hours, while the Viedma ripening of decacyclene was also demonstrated over a period of ca. 15 days. Viedma ripening provides non-equilibrium conditions that promote secondary nucleation through enantiomer-specific oriented attachment non-classical crystal growth.
Non-stochastic conglomerate crystallization from achiral building blocks is surprisingly common and not well understood. Herein, one of the earliest examples was investigated, where an overwhelming imbalance (134 right-handed crystals, 5 left-handed crystal) was confirmed in the conglomerate crystallization of magnesium sulfate heptahydrate (MgSO4·7H2O), epsomite. In such cases, it is believed that hidden chiral (cryptochiral) environments that influence the primary crystal nucleation are to blame. As such, chiral additives (L- and D-asparagine) were used to influence the mirror symmetry breaking in epsomite crystallization. The chiral distribution resulting from the conglomerate crystallization of achiral molecules is fascinating since it may provide insight regarding polymorphism and the outstanding question of the origin of biological homochirality.