The effect of the molecular structure in the polymorphic crystallization was investigated by the rapid cooling method in ethanol solutions using BPT methyl ester (Me-est: Methyl 2-(3-Cyano-4-(2-methylpropoxy)-phenyl)-4-methyl-thiazole-5-carboxylate) and BPT propyl ester (Pr-est: Propyl 2-(3-Cyano-4-(2-methylpropoxy)-phenyl)-4-methyl-thiazole-5-carboxylate). The crystallization of Me-est resulted in only one crystal form at every initial concentration. On the other hand, in the crystallization of Pr-est at high initial concentrations, meta-stable A form first appeared, and after then, the stable B form nucleated and the solution-mediated transformation occurred. At low initial concentrations the stable form directly crystallized. Crystallographic analysis indicated that the Me-est crystal is constructed by stacking the flat sheet of the molecules that are formed by the two hydrogen bonding between a couple of molecules. Both of the stable and meta-stable forms of Pr-est are constructed also by stacking the sheet structures of the molecules. In the meta-stable form no hydrogen bonding was observed in the crystal, however, the structure of the stable form is stabilized by the hydrogen bonding through nitrile and carbonyl group. These results indicate that even the small change in molecular structure give rise to the large difference of the polymorphic nucleation behavior and crystal structure. The solvent effect on the polymorphic nucleation behavior of the Pr-est was also examined. From c-Hxn solution two polymorphs appeared and the same transformation was observed as that in EtOH. However, from MeCN solution the stable form directly crystallized.
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Kitamura, M., Hara, T. (2009). Effect of Molecular Structure on Polymorphic Nucleation of BPT Derivatives. In: Åžener, B. (eds) Innovations in Chemical Biology. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6955-0_11
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DOI: https://doi.org/10.1007/978-1-4020-6955-0_11
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