Solubility determination and crystallization thermodynamics of an intermediate in different organic solvents

Abstract

This study reported the solid–liquid equilibrium solubility of 4-nitropyrazole at the temperature ranging 288.15 K to 328.15 K in methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, isobutanol, 1-pentanol, isoamyl alcohol, acetonitrile, acetone, methyl acetate, ethyl acetate, tetrahydrofuran and water, respectively. All the experiments were performed with the gravimetric method under the ambient pressure of 0.1 MPa. At the temperature ranging from 288.15 K to 328.15 K, 4-nitropyrazole in methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, isobutanol, 1-pentanol, isoamyl alcohol, acetonitrile, acetone, methyl acetate, ethyl acetate, tetrahydrofuran and water exhibited the mole fraction solubility values of 0.109034–0.365964, 0.101321–0.310165, 0.087146–0.312564, 0.048152–0.238024, 0.079024–0.282653, 0.054890–0.247235, 0.071382–0.275687, 0.062864–0.21521, 0.039062–0.135087, 0.038140–0.058187, 0.007271–0.027222, 0.004829–026068, 0.004126–0.021975 and 0.002174–0.015095, respectively. The acquired solubility data of 4-nitropyrazole in the selected solvents was correlated with the modified Apelblat equation, λh equation, the ideal equation, as well as the polynomial empirical equation. Next, the correlated values of the four equations were significantly consistent with the experiment values, and the polynomial empirical equation yielded more effective correlated results than other equations. In addition, the solvent effect on 4-nitropyrazole solubility was investigated with Kamlet-Taft parameters. Moreover, to clarify the sequence of solubility in a range of solvents, the molecular modeling studies were conducted. Activity coefficient was to access the solute–solvent molecular interactions. Furthermore, the thermodynamic properties exhibited by 4-nitropyrazole (i.e., standard dissolution enthalpy (ΔdisHo), standard dissolution entropy (ΔdisSo) and standard dissolution Gibbs free energy (ΔdisGo)) in the selected solvents were characterized and then discussed from the experiment data. Besides, ΔdisHo, ΔdisSo and ΔdisGo at mean temperature in different pure solvents reached 22.40 kJ̣·mol−1-38.07 kJ̣·mol−1, 58.21 J̣·K-1̣·mol−1-81.10 J̣·K-1̣·mol−1 and 4.20 kJ̣·mol−1-13.13 kJ̣·mol−1, respectively. As revealed from the result, 4-nitropyrazole in solvents selected showed a non-spontaneous and entropy-driven dissolution. The present study could present the fundamental data to separate 4-nitropyrazole.