In the industrial production of chloramphenicol, a ternary azeotrope consisting of isopropanol, benzene and water exists. A new process for the extractive distillation of recycling benzene and isopropanol from wastewater by mixed entrainer was proposed. Quantum chemical analysis and relative volatility analysis were employed to screen suitable entrainers. The multi-objective optimization scheme was established to determine the basic process parameters such as such as composition and ratio. Thermal coupled extractive distillation process and heat pump with an assisted extractive distillation process were used to improve energy saving. Subsequently, the interaction energy between the entrainer and the system was computed via molecular dynamics, and different processes are evaluated by economic analysis, environmental analysis, energy consumption analysis and exergy analysis. The results indicated that the optimal mixed entrainer under decompression pressure, it was 40.37 % dimethyl sulfoxide +59.63 % glycerol. The thermally coupled extractive distillation process 1 has the best economic benefits and has good thermodynamic efficiency and environmental advantages. Compared with ethylene glycol extractive distillation process, total annual cost is reduced by 16.93 % and gas emissions is reduced by 43.19 %.