Wei Deng, Y Li, Juncong Wu, Zong Yang Kong, Joo Yee Heah, Jun Zhang, Zhigang Lei, Ao Yang
Abstract Recent studies have shown that hybrid ionic liquid (IL)‐deep eutectic solvent (DES) systems exhibit synergistic physicochemical properties in various applications. Such promising findings had motivated us to conceptually explore the feasibility of hybrid IL + DES entrainers for extractive distillation by integrating COSMO‐RS screening, process simulation, and multi‐objective optimization. The optimum system, 1,1‐dimethylpyrrolidinium isopropoxide ([DMPyrr][iPrO]) and methyl tributyl ammonium acetate: tartaric acid (1: 1) (i.e., MTBAA: TA (1: 1)), achieves reductions of 29.81% in total cost and 28.26% in carbon emissions compared to conventional ethylene glycol entrainer. Quantum chemical analysis reveals that the hybrid solvent strengthens intermolecular interactions with target components, outperforming single IL entrainers. These findings demonstrate that IL‐DES synergy can be effectively leveraged to enhance separation performance while reducing environmental impact.