Study on 2-amino-4-chloro-6-methoxypyrimidine in four binary solvent mixtures: Solubility measurement, calculation, preferential solvation and extended Hildebrand solubility parameter approach analysis

Equilibrium mole fraction solubility of 2-amino-4-chloro-6-methoxypyrimidine in methanol/ethanol/acetone/ N,N -Dimethylformamide (DMF) plus water was experimentally measured by isothermal saturation method at 278.15–323.15 K under 101.2 kPa. The mixed solvents with low moisture and high temperature played a supportive role in the dissolution of 2-amino-4-chloro-6-methoxypyrimidine. The amount of 2-amino-4-chloro-6-methoxypyrimidine dissolved in DMF + water was more than that in other three systems and the ranges of values for the solubility (mole fraction) of 2-amino-4-chloro-6-methoxypyrimidine in methanol/ethanol/acetone/DMF + water were 0.0002046–0.009616, 0.0002046–0.01060, 0.0002046–0.04918 and 0.0002046–0.1197, respectively. The Jouyban-Acree (JA), Apelblat-Jouyban-Acree (AJA) and van’t Hoff-Jouyban-Acree (VJA) model were applied to calculate the solubility data of 2-amino-4-chloro-6-methoxypyrimidine in mixtures. The preferential solvation parameter δx 1,3  > 0 in 0.32 <  x methanol  < 1, 0.24 <  x ethanol  < 1, 0.21 <  x acetone  < 1 and 0.19 <  x DMF  < 1, the 2-amino-4-chloro-6-methoxypyrimidine was preferentially dissolved by cosolvents and the 2-amino-4-chloro-6-methoxypyrimidine was dissolved preferentially by water within δx 1,3  < 0. What’s more, the interaction between solute - solvent molecules and the internal interaction of molecules was analyzed by extend Hildebrand solubility approach (EHSA) and in the concentration range with W  >  δ 1+2 δ 3 , the hydrophobic groups in the 2-amino-4-chloro-6-methoxypyrimidine played a dominant role, while in other ranges self associations of solute, solvent or both were observed. The dissolution thermodynamic properties were obtained by van’t Hoff plots and the ranges of values for Δ sol H o (kJ∙mol −1 )/ Δ sol G o (kJ∙mol −1 )/ Δ sol S o (J∙mol −1 ) were 9.74 – 31.12, −17.84 – 4.96 and 33.79 – 161.89.