Site‐selective recognition and continuous separation of magnolol isomers via hydrogen‐bond‐driven associative extraction

Abstract Magnolol (MAG) and honokiol (HON) are a pair of typical positional isomers that are difficult to separate due to their highly similar physicochemical properties. In this study, 1,3‐dimethylurea (DMU) was screened from 46 candidates as the optimal extractant using the COSMO‐RS model, and a cyclohexane/aqueous DMU biphasic extraction system was constructed. Fourier transform infrared spectroscopy, 1 H NMR, and molecular dynamics simulations revealed the site‐selective recognition mechanism of DMU toward HON. The 4′‐OH of HON is preferentially hydrated at the polar interface due to its high spatial accessibility, releasing 2‐OH for selective hydrogen bonding with DMU. MAG cannot effectively bind DMU due to intramolecular hydrogen bond‐induced conformational locking. A process combining continuous fractional extraction with concentration‐swing back‐extraction was further developed. Simulations predicted product purities above 99.0% and overall recoveries above 98.9% for both isomers. The proposed process also enables closed‐loop extractant recycling.