Solubility Determination and Correlation Analysis of 5‑Chloropyrazin-2-Amine in Several Mixed Solvents

In this study, the solubility of 5-chloropyrazin-2-amine in four aqueous solutions (methanol, ethanol, n-propanol, and ethylene glycol (EG)) plus water was determined by a gravimetric method at temperatures ranging from T = 278.15 to 323.15 K at 101.2 kPa pressure. Experimental results indicated that 5-chloropyrazin-2-amine solubility positively increased with increasing temperature at a given solvent composition and decreased with increasing mass fraction of water in each system. The order of solubility from high to low on the mole fraction scale was as follows: methanol (0.02007, 323.15 K) > ethanol (0.01308, 323.15 K) > n-propanol (3.827 × 10–3, 323.15 K) > water (1.569 × 10–3, 323.15 K). Similarly, the solubility of 5-chloropyrazin-2-amine was higher in (methanol + water) than in the other three cosolvent mixtures. The solid phase crystal of 5-chloropyrazin-2-amine was tested by X-ray powder diffraction (XPRD) and the results showed no polymorphic transformation, solvate formation, or crystal transition during entire experiments. The experimental solubility values of 5-chloropyrazin-2-amine were correlated by three thermodynamic models. The results show that the largest relative average deviation (RAD) and root mean square deviation (RMSD) data were no more than 5.38% and 2.34 × 10–4, respectively. The Jouyban–Acree model gave the best correlation result in this study.