Cocrystal Formation in L-Menthol/Phenol Eutectic System: Experimental Study and Thermodynamic Modeling

Deep eutectic solvents (DESs) are eutectic mixtures containing a hydrogen-bond acceptor and donor, forming a mixture with a significantly lower melting temperature than those of its pure constituents. DESs containing cyclohexyl and phenolic alcohols draw particular attention due to the observed large depression in the melting temperature of the mixture. The present study investigates in detail the solid-liquid equilibria (SLE) in the l-menthol/phenol eutectic system. Differential scanning calorimetry and powder X-ray diffraction (XRD) analysis were employed to obtain the phase diagram. Two cocrystals were identified with 1:2 and 2:1 ratios. The crystal structures were determined by single-crystal and powder XRD techniques. The SLE data were correlated using the nonrandom two-liquid (NRTL) model and the conductor-like screening model for realistic solvation (COSMO-RS). The two eutectic points determined by the NRTL and COSMO-RS models are x(e,1)(NRTL) = 0.69, T-e,1(NRTL) = 273.1 K, x(e,2)(NRTL) = 0.47 T-e,2(NRTL) = 261.3 K, x(e,1)(COSMO) = 0.70, T-e,1(COSMO) = 272.8 K, and x(e,2)(COSMO) = 0.48 T-e,2(COSMO) = 261.5 K, which are in good agreement with the experimental eutectic temperatures.