Effects of solvent composition and temperature on polymorphism and crystallization behavior of thiazole-derivative

Abstract

The thermodynamic stability and transformation behaviors of the polymorphs (A and C) and solvated crystals (BH (BPT·0.5H 2O) and D (BPT·MeOH)) of the thiazole-derivative (BPT) were investigated. The thermodynamic stability and the transformation behavior were examined in relation with the chemical potential and the solubility of BPT in each crystal. The C form is basically the stable form and the A form is the metastable form at every temperature and methanol compositions ( V MeOH). However, the stability of BH and D forms remarkably changes with temperature and the methanol compositions. At 323 K with methanol compositions of 0.7 and 0.8 A, BH and D forms transformed to the stable form, C. However, at 0.5 of V MeOH A and D forms do not transform to the stable C form directly, but transform to the other metastable form of BH. This result may indicate the preferable nucleation and growth of BH crystals due to the specific solute–solvent interaction in comparison with C crystals. The small chemical potential difference between BH and C forms may also stabilize the BH form. The increase in the stability of D crystals and the decrease in the stability of BH with the methanol composition was related to the dissociation equilibrium of each crystal. At 313 K the BH form transformed to the other metastable form, D, while transforming to the stable form C. The transformation from the hydrated BH to the solvated D crystal seems to be relatively easy because of the similar configurations of carboxylic acid group in BPT. The thermodynamic stability of the solvated crystals of BH and D decreases with temperature. It is considered that the dissociation of both BH and D crystals is accelerated with increase of temperature. In the crystallization on adding water to BPT solution of methanol and water mixture, it became clear only the metastable form of A and B crystallizes and the crystallization of A form is remarkably accelerated by increasing the addition rate of water.