Toward Sustainable Separation of Complex Azeotropic Mixture Methanol–Ethanol–Tetrahydrofuran Based on the Ionic Liquids Screening, Global Optimization, and Mechanism Analysis

Ionic liquids (ILs) have long been recognized as highly effective solvents for azeotrope separation and have attracted significant research attention over the past two decades. In this study, environmentally friendly and efficient ILs were screened using the COSMO-RS model for the separation of the ternary azeotropic mixture methanol/ethanol/tetrahydrofuran. Among the 4557 ILs, the ethyltrimethylammonium 2,2-dichloroethoxide (i.e., [EtMe3N]­[DCE]) was identified as a promising solvent based on its selectivity, capacity, and compliance with thermodynamic constraints. To further optimize the process, the nondominated sorting genetic algorithm-II (NSGA-II) was applied. The resulting processes were systematically evaluated in terms of economic performance and environmental impact. The results demonstrated that using [EtMe3N]­[DCE] and a mixed solvent ([EtMe3N]­[DCE] + dimethyl sulfoxide (DMSO)) reduced economic costs by 30.65% and 19.37%, and environmental burdens by 42.50% and 33.13%, respectively, compared with the conventional DMSO-based process. In the LCA, environmental impacts were further reduced by 98.32% and 31.69%, respectively. To gain molecular-level insight, quantum chemical calculations were performed to elucidate the separation mechanism. The analysis revealed that ethanol exhibited the strongest interaction with ILs, followed by methanol, while tetrahydrofuran displayed the weakest affinity, consistent with the COSMO-RS predictions. Overall, this study establishes a systematic framework for screening sustainable ILs for the separation of ternary azeotropic systems.