Chemo-enzymatic Synthesis Of(R)-Epichlorohydrin Based On 3-chloro-1,2-propanediol Recycle

Chiral epichlorohydrin is a very important C₃ chiral synthon which was widely used in material,pesticide,chemical,medical and other field.In recent years,with the maturing technology and the application of a large-scale synthesis of epichlorohydrin from glycerol which is a by-product of biodiesel,the market price of epichlorohydrin has fallen.Therefore,the kinetic resolution of racemic epichlorohydrin by epoxide hydrolase had been one of the most effective ways for synthesis of chiral epichlorohydin.However,the theoretical yield of chiral epichlorohydrin would not exceed 50%by conventional kinetic resolution,and the material utilization rate was too low,to restrict its industrial application potential.In order to further improvethe atom economy in this process,the by-product of 3-chloro-1,2-propanediol was recycled to prepare racemic epichlorohydrin through chlorination and cyclization reaction to make the total yield of（R）-epichlorohydrin been improved which was based on synthesis of（R）-epichlorohydrin by kinetic resolution of racemic epichlorohydrin with epoxide hydrolase in this paper.The results were showed as follows:In order to improve the stability and batch,the immobilization of epoxide hydrolase was studyed in this thesis.The modified epoxy resin was taken to immobilize the epoxide hydrolase and then the condition of immobilization was optimized.The optimum temperature and pH were 15 C and 8.0,respectively.The amount of enzyme was 8.04 mg/mL and the time of immobilization was 24 h.The protein loaded and activity recovery of immobilized enzyme can reach its maximum value of 78.43%and 71.5%after optimization.The catalytic characteristic of immobilized enzyme was studyed and showed that the pH stability,thermal stability and storage stability of the enzyme are significantly improved after immobilization compared with the free enzyme.The immobilized enzyme still retain more than 80%enzyme activity after six recycles,which suggested the immobilized enzyme had a good operation stability.The best yield were 28.96%（e.e.>99%）when using the immobilized enyzme for preparing（R）-epichlorohydrin by kinetic resolution of 1.5%（v/v）racemic epichlorohydrin.By-product of 3-chloro-1,2-propanediol was taken as raw material for preparing racemic epichlorohydrin and thenthe optimal conditions of chlorination and cyclization reaction were obtained.The optimal chlorination conditions were as follows:6%（w/w）adipic acid was taken as catalyst.The reaction temperature was 110℃,9%（w/w）blue silica gel was taken as desiccant and reacted for 6 h.During this conditions,the yield of 1,3-dichloropropanol reached 85.34%.The optimal cyclization conditions were as follows:NaOH was used in the cyclization reaction,Mole ratio of NaOH and 1,3-dichloropropanol was 1.2:1.the reaction temperature was 50℃.Under these conditions,the yield of epichlorohydrin reached 80.6%.The process of the extraction of reaction product and cyclic synthesis of（R）-epichlorohydrin was investigated.The optimal extraction conditions of（R）-epichlorohydrin showed as follows.Methylene chloride was taken as extracting agent and extraction temperature was 25℃,the volume of extractant and liquid was 2:1.The extraction time was 20 min,number 2,During this conditions the extraction yield of（R）-epichlorohydrin reached 99.6%.The process of using epoxide hydrolase for synthesis of（R）-epichlorohydrin by kinetic resolution of racemic epichlorohydrin was set up based on the by-product recyle utilization.After fifth recycles 3-chloro-1,2-propanediol to prepare racemic epichlorohydrin,the actual yield of（R）-epichlorohydrin reach to 52.2%（e.e.>99%）compared with the before cycle（28.7%）,which increased by 81.9%.