Cooperative Hydration and Hydrogen-Bond Regulation in Salt–Sugar Hybrid Media Enables Exceptional Alcohol–Water Demixing

Efficient recovery of biobutanol from concentrated fermentation broths is hindered by strong alcohol–water interactions and azeotrope formation. Herein, salt–sugar hybrid systems composed of glucose and potassium salts were developed to investigate the synergistic effects of salting-out and sugaring-out in butanol–water mixtures. Different from single salting-out or sugaring-out systems that suffer from saturation limitation at low total solute concentration, this work reveals a cooperative solvation regulation mechanism combining ionic hydration and hydrogen-bond network reconstruction, and realizes an expanded effective phase-separation operating window up to 700 g·kg–1. The hybrid systems significantly enhanced phase separation, achieving butanol recoveries above 99.5%, dehydration efficiencies up to 96%, and water contents as low as 2.28 wt % in the butanol-rich phase. Mechanistic studies revealed that highly hydrated salt ions strongly compete for water molecules, while glucose regulates the hydrogen-bond network and stabilizes phase interfaces. Such salt–sugar complementarity alleviates high-salt-induced viscosity rise and phase-interface deterioration, avoiding premature separation saturation of single-agent systems. This cooperative solvation regulation weakens alcohol–water association, promotes liquid–liquid demixing, and expands the effective phase-separation region. The findings not only provide fundamental insights into coupled salting-out and sugaring-out phenomena, but also offer a green, energy-efficient strategy with great application potential for biofuel purification and alcohol dehydration in practical fermentation–separation coupling processes.