The effect of solvent on the crystallization behavior of the polymorphs of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid (BPT) was investigated under rapid cooling. From methanol (MeOH) and ethanol (EtOH) solutions, only the solvated crystals of the D forms of methanol (D(MeOH)) and ethanol (D(EtOH)) crystallized. Both D forms are stable and have similar crystal structures. However, the solubility of the D(EtOH) form is 1.5 times higher than that of the D(MeOH) form. With the release of alcohol molecules, both D forms transformed to the C form with an increase in temperature for the DSC measurement. After that, the C form transformed to the A form via a melt-mediated mechanism. The release temperature of alcohol was higher for D(EtOH) than for D(MeOH). When the crystallization was performed in 1-propanol (1-PrOH) and 2-propanol (2-PrOH), the metastable A form preferentially crystallized. On the other hand, in acetonitrile (MeCN) solutions the stable C form was selectively obtained. These crystallization behaviors in each solvent did not depend on supersaturation in solutions. The FTIR spectra of BPT in EtOH and 1-PrOH suggested that BPT molecules in solution take a conformation similar to that in each crystal. These results suggest that the solvent effect is controlled by the thermodynamic equilibrium properties such as the conformation of the solute and the solute–solvent interactions rather than the crystallization kinetics of the polymorphs. Furthermore, the solution-mediated transformation rate from the A form to the C form is higher in MeCN than those in 1-PrOH and 2-PrOH. In the mixed solvents of 1-PrOH and MeCN with water, the same polymorphs crystallized as those obtained in pure solvents in the water volume fraction up to the range of 0.1. However, the hydrated crystals (BH form) predominantly crystallized with further addition of water. Solubility measurements suggested that such behavior is related to the solvated structure surrounding the BPT molecule.
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