Solubility Behavior and Data Correlation of N-Acetyl-l-valine in 12 Individual Solvents at Multiple Temperatures

N-Acetyl-l-valine is a crucial pharmaceutical intermediate, and research on the solubility behavior of N-acetyl-l-valine in organic solvents is necessary for processes of crystallization and separation. The solubility data of N-acetyl-l-valine in 12 pure solvents (water, 2-butanone, dimethyl carbonate, n-propanol, isopropanol, n-butanol, isobutanol, acetone, acetonitrile, methyl acetate, ethyl acetate, and 1,4-dioxane) ranging from 283.15 to 323.15 K were measured by the static gravimetric method. Its solubility in all studied solvents increases with the increase of temperature. Moreover, the solubility sequence at 298.15 K is n-propanol > isopropanol > n-butanol > isobutanol > 1,4-dioxane > acetone > 2-butanone > water > methyl acetate > ethyl acetate > acetonitrile > dimethyl carbonate. The solubility behavior is primarily determined by the solvent polarity (ET(30)), hydrogen bonding, and cohesive energy density. Hirshfeld surface analysis (HS) and molecular electrostatic potential surface (MEPS) analysis were used to determine the internal interactions within N-acetyl-l-valine solutions. Four solubility fitting models were used to correlate the experimental mole fraction solubility data, including the modified Apelblat model, the λh equation, the NRTL model, and the UNIQUAC model. Furthermore, the NRTL model was utilized to calculate the mixing thermodynamic characteristics of N-acetyl-l-valine in these solvents. The results indicated that the mixing process was entropy-driven and spontaneous.