Chirality Scaffolding Crystallization

Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo* Kuroda Chiromorphology Team, JST ERATO-SORST**
â—‹Reiko Kuroda* Sayoko Hasebe* Yoshitane Imai** Tomohiro Sato**

The polymorphism, a phenomenon to have crystals with the same composition but different structure, is of importance in pharmacology, solid-state chemistry, material science etc. Polymorphs usually differ in their chemical and physical properties such as melting point, density and lattice energy. Chiral crystals exhibit favorable properties, but are often meta stable and difficult to obtain selectively. The mechanism and control of polymorphism is not yet well understood. Here, we report a control of polymorphism of 2-arylthio-3-methylcyclohexen-1-one (compound I) under various conditions. Four polymorphs, a - d (a, b: achiral crystals, c, d: chiral crystals), were obtained which exhibit similar density and melting point. Crystal a is the most stable and was obtained most frequently. When polar solvent with hydroxyl groups was used, crystal c was sometime produced. Chirality recognition was observed, when I was crystallized in the presence of a chiral organic compound, II, where chirality control appears to be achieved in two steps: first, crystal I-c with a bigger (001) plane grew on top of the substrate, II, which also exposed a unusual crystal face. Then, crystal I-d grew on the (001) plane of I-c. We named this 'scaffolding crystallization'. Epitaxial growth was observed between the overlayer I-d and the substrate I-c. Chirality is recognized in both steps, and particularly in the latter step, 100% chirality transfer was achieved. Crystallization from the melt was found to produce different polymorphs depending on the crystallization speed. Various techniques including single or powder crystal X-ray diffractometry, 2D-NMR and DSC are used to analyze the interesting crystallization behaviour.