Solubility Measurement and Modeling of 2-Amino-4,6-dichoropyrimidine in Ten Pure Solvents and (Ethyl Acetate + Ethanol) Solvent Mixtures

Abstract

The basis of purification and further theoretical studies of 2-amino-4, 6-dichoropyrimidine is the solubility and solution thermodynamics in different solvents. In this paper, the solubility of 2-amino-4,6-dichoropyrimidine in 10 neat solvents (methanol, ethanol, n-propanol, isopropanol, acetone, acetonitrile, ethyl acetate, 1,4-dioxane, toluene, and cyclohexane) and binary liquid mixtures (ethyl acetate + ethanol) was measured by the isothermal saturation method at temperatures range from 278.15 to 318.15 K, at p = 101.2 kPa. High-performance liquid chromatography (HPLC) was used to analyze the solubility of 2-amino-4,6-dichoropyrimidine in selected solvents. To sum up, the equilibrium mole fraction solubility was highest in 1,4-dioxane (2.619 × 10 −2 at 318.15 K) and lowest in cyclohexane (0.02238 × 10 −2 at 318.15 K), and ranked as 1,4-dioxane (2.619 × 10 −2 at 318.15 K) > acetone (1.630 × 10 −2 at 318.15 K) > ethyl acetate (1.471 × 10 −2 at 318.15 K) > acetonitrile (0.5048 × 10 −2 at 318.15 K) > methanol (0.3888 × 10 −2 at 318.15 K) > ethanol (0.3391 × 10 −2 at 318.15 K) > n-propanol (0.3133 × 10 −2 at 318.15 K) > toluene (0.2737 × 10 −2 at 318.15 K) > isopropanol (0.2574 × 10 −2 at 318.15 K) > cyclohexane (0.02238 × 10 −2 at 318.15 K). The achieved solubility values in monosolvents were correlated by the modified Apelblat equation, λh equation, Wilson model, and NRTL model and in solvent mixtures by three cosolvency models including Jouyban-Acree model, van't Hoff-Jouyban-Acree model, and Apelblat-Jouyban-Acree model. Calculated results fitted well with experimental data. Consequently, for the monosolvents, the values of rootmean-square deviation (RMSD) and relative average deviation (RAD) were less than 0.58 × 10 −4 and 0.80%, respectively, and for the binary solvent mixtures were 0.49 × 10 −4 and 0.46%. Furthermore, the Gibbs energy, mixing enthalpy, mixing entropy, activity coefficient at infinitesimal concentration (γ 1 ∞ ) and reduced excess enthalpy (H 1 E,∞ ) in monosolvents, and dissolution property in mixed solvents were computed. The mixing process of 2-amino-4,6-dichoropyrimidine in the studied solvents was spontaneous and endothermic. The obtained solubility and thermodynamic studies would be used to optimize the purification process of 2-amino-4,6-dichoropyrimidine.

Solubility and Thermodynamic Modeling of Sulfanilamide in 12 Mono Solvents and 4 Binary Solvent Mixtures from 278.15 to 318.15 K

“…The van’t Hoff–Jouyban–Acree model is the combination of the van’t Hoff model shown in eq and the Jouyban–Acree model shown in eq , and the mathematical representation of this model shown in eq . − van’t Hoff–Jouyban–Acree equation is ideal, which relates the dependence of the logarithm of mole fraction solubility of the solute upon the inverse proportion of temperature. where x w , T is the mole fraction solubility of sulfanilamide in binary solvent mixtures at the temperature T in kelvin, w 1 and w 2 denotes the mass fraction of solvent 1 (acetone) and solvent 2 (methanol, ethanol, ethyl acetate, and toluene) in the absence of solute (sulfanilamide), and A 1 , B 1 , A 2 , B 2 , and J i are the model parameters of van’t Hoff–Jouyban–Acree model and were determined by solubility fittings.…”

“…The Apelblat–Jouyban–Acree equation is a semiempirical model employed to correlate the solubility of a solute against the solvent composition at the same time absolute temperature and described in eq . This model is developed by combining eq and eq . ,− Here A 1 , B 1 , C 1 , A 2 , B 2 , C 2 , and J i are the model parameters of the Apelblat–Jouyban–Acree model.…”

Measurement of the Solubility of Diclazuril and Discussion of the Effect of the Cosolvent

“…The isothermal saturation method was used to study the solid–liquid equilibrium for diclazuril at the temperature range from 283.15 to 323.15 K. − Our previous work has verified the reliability of the experimental method …”

“…The isothermal saturation method was used to study the solid−liquid equilibrium for diclazuril at the temperature range from 283.15 to 323.15 K. 10−12 Our previous work has verified the reliability of the experimental method. 13 The solvent mixtures were prepared by using the analytical balance (CPA225D). Excess diclazuril and about 60 mL of solvent were added into a 100 mL glass vessel for each experiment.…”

Solubility Measurement and Thermodynamic Properties of Levetiracetam in Pure and Mixed Solvents

“…The solid–liquid equilibria for the monosolvent and the solvent mixtures systems were measured by the isothermal saturation method in the temperature range of 283.15 to 323.15 K, − and the solubility of levetiracetam was tested by HPLC.…”