Nonideality and cocrystal formation in l-menthol/xylenol eutectic systems

• The solid–liquid phase diagram of five L-menthol/xylenol eutectic systems was measured. • Three cocrystals were observed in the studied eutectic systems, and a new 3,4-xylenol polymorph was identified. • L-menthol does not form cocrystals with xylenol isomers bearing a methyl group at position 2. • COSMO-RS with the TZVP and TZVPD_FINE parameterizations was used to predict the phase diagrams. • COSMO-RS predicts well the eutectic points of the studied systems. Nonideality and cocrystal formation affect the solid–liquid equilibria (SLE) in eutectic systems. This study investigates the influence of the molecular structure of xylenol (dimethylphenol) isomers on the nonideality and cocrystal formation in eutectic systems containing L-menthol and five different xylenol isomers. Differential scanning calorimetry and powder X-ray diffraction analyses were employed to comprehend the SLE phase diagram of the studied systems. L-Menthol did not form cocrystals with xylenol isomers having a methyl group at position 2. In contrast, two cocrystals were observed in the L-menthol/3,4-xylenol systems at 1:2 and 2:1 ratios, and one cocrystal was observed in the 1:1 L-menthol/3,5-xylenol system. The liquid phase of all systems showed a strong negative deviation from ideality, except the L-menthol/2,6-xylenol eutectic system, which exhibited a near-ideal behavior. The nonideality of the liquid phase was modeled using the conductor-like screening model for realistic solvation (COSMO-RS) using TZVP and TZVPD_FINE parameterizations, finding that COSMO-RS can reasonably describe the liquid phase nonideality and predict the SLE phase diagram of simple eutectic systems and systems with cocrystal formation.