Tuning organic crystal chirality by enantiomer-specific oriented attachment

Abstract

Enantiomer-specific oriented attachment (abbreviation ESOA), a non-classical crystallization phenomenon, has been used for chiral crystal separation since Viedma for symmetry breaking of chiral substances. The so-called enantiomer-specific oriented attachment is mainly manifested by spontaneous chiral recognition of neighboring crystals during self-assembly through specific crystal faces, which leads to chiral amplification, and thus the possible formation of purely chiral crystal aggregates. However, as of now, this method enables chiral separation of achiral molecules, while it is rarely applied in the chiral separation of conglomerates. In view of this, we verified the stability and practicality of the ESOA method in chiral crystal separation by N-benzoylglycine and N-succinopyridine from the perspective of achiral molecules and conglomerates, respectively. Besides, we tried to explore whether ESOA can be used for the resolution of racemic compounds. To this aim, we boiled ethanol aqueous (V_EtOH : V_Water = 3 : 2) saturated solutions of DL-isoleucine, DL-leucine or DL-valine, but did not succeed in obtaining a single chiral crystal agglomerate. This is not the result we expected, but it reinforces the fact that most of the conditions for the success of the ESOA method are that the chiral substrate is a conglomerate. And it appears that we have discovered a way to prepare a conglomerate of DL-isoleucine, DL-leucine, and DL-valine on a large scale by this method, with a view to playing a role in other special complex chiral drugs in the future.