Determination and analysis of 4-hydroxyphenylacetamide solubility in different solvents by Hansen solubility parameters, solvent effect and thermodynamic properties

4-Hydroxyphenylacetamide (HPAD) is commonly used in the synthesis of high value-added chemicals in the fields of medicine, food and agriculture, such as atenolol, p-hydroxyphenylacetic acid, L-phenylalanine and D- phenylalanine. HPAD relies on chemical synthesis, involving multi-step reactions and multiple chemical catalysts. It is crucial to select appropriate organic solvent to improve yield and purity. In this work, the solubility of HPAD in 12 pure solvents (water, acetonitrile, methanol, ethanol, n-propanol, isopropanol, n-butanol, n-hexane, n-heptane, methyl acetate, ethyl acetate, n-butyl acetate) and 3 binary solvents (n-hexane + methanol, acetonitrile + methanol, n-heptane + methanol) was investigated in the range of 278.15-323.15 K. The solubility of HPAD in the selected solvents was positively correlated with the temperature. Hansen solubility parameters were used to study the dissolution behavior of HPAD. Then, the solvent effect was analyzed by KAT-LSER model, and it was found that the hydrogen bond acidity and nonspecific dipolarity/polarizability of solvents favored the dissolution of HPAD. Moreover, the modified Apelblat model (MA model), lambda h model, CNIBS/R-K model (CNK model), Jouyban-Acree model (JA model), and SUN model were used to fit and analyze experimental data. The results showed that the MA model and the CNK model were the best models for single and binary solvents, respectively. Finally, van't Hoff analysis showed that the dissolution of HPAD in the selected solvents was an endothermic and entropic driven process. This work provided reference data for the separation, purification and crystallization of HPAD, and had certain guiding significance for its industrial production and application.