Extraction of n-Butanol from Water Using Hydrophobic Deep Eutectic Solvents: A Combined Approach of COSMO-RS Screening, Liquid–Liquid Equilibrium, and Molecular Simulation

The industrial production of biobased n-butanol is primarily hindered by the high cost of separation, which results from its low concentration in the fermentation broth and the formation of a water–n-butanol azeotrope. Liquid–liquid extraction is a preferred separation method for azeotrope separation, with efficacy dependent on extractant choice. Thymol/carvacrol (hydrogen-bond donors, HBDs) and C8–C10 fatty acids (hydrogen-bond acceptors, HBAs) were selected based on COSMO-RS predictions and consideration of HDESs’ physicochemical properties. Six HDESs with varying compositions were synthesized. The liquid–liquid equilibrium (LLE) data for the corresponding water (1) n-butanol (2) and HDES (3) systems were measured at 303.15 K and 101.3 kPa. The effects of HBD structure, HBA chain length, and HBD/HBA ratio were systematically studied. The data were correlated with the NRTL model, and the extraction mechanism was elucidated via molecular dynamics (MD) simulations. All six HDESs proved effective for separating n-butanol from water, with HDES5 (thymol-capric acid, 1:1) identified as the optimal extractant. Extraction performance is governed by three key factors: thymol outperforms carvacrol as the HBD, longer fatty-acid alkyl chains enhance selectivity, and a higher thymol-to-acid molar ratio strengthens interactions. The NRTL model reliably correlates the experimental data. MD simulations confirm that van der Waals forces dominate the extraction.