Separation Of α-Cyano-3-phenoxybenzyl Alcohol From Its Acetate Using Liquid-Liquid Extraction

(S)-α-Cyano-3-phenoxybenzyl alcohol ((S)-CPBA) is an important chiral building block for the preparation of many high-level activity pyrethroid insecticides. Its optically active derivatives, such as a-hydroxy acid, a-hydroxy ketone and 6-hydroxy amine, are important for the production of pharmaceuticals and agrochemicals. Many methods can be used to prepare (S)-CPBA. Among them, the lipase-catalyzed asymmetric alcoholysis of α-Cyano-3-phenoxybenzyl acetate (CPBAc) should be especially mentioned because high optically pure (S)-CPBA can be obtained. This reaction is shown in scheme 1. During the resolution of racemic CPBAc by alcoholysis, (S)-CPBAc would be deacylated preferably if lipase showed high enantioselectivity. The undesired (R)-CPBAc can be easily racemized and reused. From Scheme 1, it can be indicated that the key step to ensure the cycle of the resolution is to separate (S)-CPBA from (R)-CPBAc efficiently.In our experiment, separation of CPBA from CPBAc by liquid-liquid extraction was investigated. The effects of the species and volume ratio of solvents on the distribution coefficients and solubility of CPBA and CPBAc in several extraction systems were also studied. Furthermore, effects of temperature and pH of water on the stability of CPBA were determined. Through screening, water:methanol:n-hexane:benzene=3:7:7:3 (volume ratio) was selected as an efficient extraction system to separate CPBA from CPBAc. At 25 ℃, after 5 extraction stages, the purity of CPBAc in the organic phase was 95.2% (mol) and the yield reached 80.6%;and the purity of CPBA in the aqueous phase was 98.8% (mol) and the yield reached 62.6%. The organic phase was dehydrated and vacuum distilled to get pure CPBAc;and the aqueous phase was extracted by benzene, then dehydrated and vacuum distilled to obtain pure CPBA.