Thermodynamic Insights into 3-Acetylcoumarin Solubility in Cosolvent Mixtures of (Methanol, Ethanol, 1-Propanol) + 1,4-Dioxane

Abstract

3-Acetylcoumarin (3AC) is a vital intermediate in pharmaceutical synthesis, particularly for the development of anticoagulant and antimicrobial agents. This study investigates the solubility characteristics of 3AC in binary solvent systems, specifically combinations of 1,4-dioxane with methanol, ethanol, and 1-propanol. The solubility was assessed over a temperature range of 288.15–328.15 K using gravimetric analysis, allowing for precise quantification of solute dissolution. Results demonstrated a consistent increase in solubility with rising temperatures, attributed to enhanced interactions and improved solute diffusion. The highest mole fraction solubility values observed were 0.0822 for 1,4-dioxane with methanol, 0.0518 for ethanol, and 0.0493 for 1-propanol at 328.15 K. The experimental mole fraction solubility data were correlated with various theoretical models, including Apelblat, Yaws, Van’t Hoff, modified Jouyban–Acree, and CNIBS/R–K models. The findings indicate that theoretical predictions closely align with experimental results, as evidenced by the small average relative deviation (ARD) and root-mean-square deviation (RMSD) values. Furthermore, Gibb’s Free energy and enthalpy were determined using Van’t Hoff equations. This investigation enhances our understanding of 3AC’s behavior in diverse solvent environments, facilitating optimized solvent selection for pharmaceutical applications and improving drug formulation processes.