Solubilities of gimeracil (form P) in aqueous co-solvent mixtures of isopropanol, N,N -dimethylformamide (DMF), ethylene glycol (EG) and dimethylsulfoxide (DMSO) were investigated via the isothermal dissolution equilibrium method at (283.15–328.15) K under ambient pressure p = 101.2 kPa. Experimental solubility was increased with increasing temperature and mass fraction of each co-solvent. The largest solubility was found in neat co-solvents. The solids equilibrated with liquid phase were characterized by X -ray power diffraction, indicating no polymorphic transformation, solvate formation or crystal transition according to the spectral data. The Jouyban-Acree model was adopted to correlate the obtained solubility. The highest RAD and RMSD values were, respectively, 2.61 × 10 −2 and 14.96 × 10 −4 . Quantitative values for the local mole fraction of DMF (EG, DMSO or isopropanol) and water around gimeracil (form P) were acquired by using the Inverse Kirkwood–Buff integrals method. The preferential solvation parameters for isopropanol were positive in the isopropanol mixtures in intermediate and isopropanol-rich compositions, which indicated that gimeracil (form P) was preferentially solvated by isopropanol. Gimeracil (form P) could act mainly as a Lewis acid interacting with proton-acceptor functional group of isopropanol. Within the same region, gimeracil (form P) was not preferentially solvated by DMF, EG and DMSO. Furthermore, the method of linear solvation energy relationships was performed with a suitable combination of solvent polarity descriptors to explain the nature of intermolecular interactions resulting in the solubility variation in the co-solvent mixtures.
Yang Cong,Cunbin Du,Meng Wang,Zhouyu Jiang,Mingliang Wang
In this work, the phase equilibrium solubility of 5-fluorocytosine (5-FC) in dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), 1-butanol, acetonitrile, 1-propanol, 1,4-dioxane, acetone, ethyl acetate, 2-propanol, 2-butanone, and mixture systems (DMSO + 2-propanol and DMF + 2-propanol) at a series of temperatures (283.15–323.15 K) is determined, and model correlation, solvent effect, and preferential solvation analysis are researched. The solubility of 5-FC is related to temperature, which decreases with decreasing temperature. For monosolvent systems, the mole solubility order is DMSO > DMF > 1-butanol > 1-propanol > 2-propanol > acetone > 2-butanone > 1,4-dioxane > acetonitrile > ethyl acetate. The solvent effect has been studied in monosolvents, hydrogen-bonding acceptor (HBA) interactions and nonspecific dipolarity/polarizability interactions favor dissolution, and solvent self-cohesiveness is not beneficial to dissolution. For two mixture systems, the mole solubility of 5-FC in DMSO + 2-propanol solvent systems is higher than that in DMF + 2-propanol solvent systems. A dimensionless parameter (δ) is defined to observe the deviation from ideality of mixed solvents whose values are all greater than zero. The equilibrium constant of the solvent exchange process (Kps) can be used to evaluate the preferential solvation of 5-FC. DMSO or DMF dissolves 5-FC in the local region around 5-FC preferentially. The equilibrium solubility data is correlated by four correlation models (modified Apelblat, λh, CNIBS/R-K, and Jouyban–Acree models). The greatest relative average deviation (RAD) and root-mean-square deviation (RMSD) values are 2.01% and 11.87 × 10–5 in pure solvent systems and 2.20% and 5.99 × 10–5 in mixture systems, respectively. These four models show excellent correlation with the experimental solubility data.
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.
危险品化学品经营许可证（带存储）