Molecular mechanism based extractant screening and process design for the separation of 2-methyltetrahydrofuran-acetonitrile azeotrope

2-methyltetrahydrofuran (2-MeTHF) and acetonitrile (ACN) are widely used as solvents in the pharmaceutical industry. As 2-MeTHF and ACN form azeotrope that cannot be separated via regular distillation. Therefore, in this study, the molecular mechanism, experiment-based extractant screening, and process design for the separation of the 2-MeTHF-ACN azeotrope were investigated. According to Fourier-transform infrared spectroscopy and density functional theory, the azeotropy was destroyed via the formation of hydrogen bonds between the extractant dimethyl sulfoxide, 2-MeTHF, and ACN. Vapor–liquid phase equilibrium experiments validated the screening results and develop a thermodynamic model of the binary system. Batch distillation experiments obtained 2-MeTHF with a mass purity of 99.6 wt% and ACN with a mass purity of 99.8 wt%. The ED process was designed using Aspen Plus and improved via the integration of the recovered waste heat (ED-HI). A sequential iterative approach was used to minimize the total annual cost (TAC). The ED-HI process resulted in reductions in the TAC, reboiler heat load, and CO 2 emissions of 20.06 %, 25.77 %, and 22.77 %, respectively, compared to those of the ED process. This study provides valuable insight into the effective separation of 2-MeTHF and ACN.