Abstract: Ionic liquids are a new type of reaction medium for the enzymatic hydrolysis of Naproxen methyl ester because they can not only enhance the water capacity but also promote the solubility of product Naproxen ((S)-(+)-2-(6-methoxy-2-naphthyl) propionic acid). In this paper, a water-saturated ionic liquid system has been selected to increase the conversion and product recovery for the hydrolysis of (R,S)-Naproxen methyl ester. Five imidazolium-based ionic liquids with different anions and organic cations were tested as the reaction medium. These ionic liquids can all facilitate the hydrolysis, but only the reaction in water-saturated ［bmim］PF6 (1-butyl-3-methylimidazolium hexafluorophosphate) proceeds rapidly and gives high conversion. The ionic liquids can slightly dissolve the lipase and make the dissolved lipase inactive. A rough correlation between the solubility of lipase in ionic liquids and its remaining activity is observed. To prevent the dissolving of lipase in ionic liquids, a nonpolar amorphous multiporous silica YWG-C6H5 with a high specific surface area has been used as the support to immobilize the lipase. Enzymatic resolution of (R,S)-Naproxen was conducted in a reactor containing immobilized lipase and water-saturated ［bmim］PF6. After 72 h reaction, 98.2% enantiomeric excess of (S)-Naproxen is obtained with 28.3% conversion. Further increasing the conversion leads to a great loss of the enantiomeric excess for the product. Based on the particular properties of ionic liquids, the reaction medium recycling, product recovery, and water recruiting have been studied. In the batch reaction, the immobilized lipase can be repeatedly used 5 times, and only a slight decrease in the conversion is found.

Key words: ionic liquid, lipase, immobilized enzyme, Naproxen methyl ester, stereoselective hydrolysis, Naproxen