Establishment Of Screening Methods For Styrene Epoxidation And The Epoxidation Of Allyl Alcohol

Objective: Majority of chiral epoxy compound possess significantbiological activity, and can synthesis many important pharmaceuticalintermediates by selective ring opening and functional transformation.Chiral styrene oxide as an important intermediate in the synthesis ofpharmaceuticals and fine chemicals has been widespread concerned.Determination of chiral epoxides commonly used chiral HPLC or gaschromatography, but systematic studies of analysis for styreneepoxidation have not been reported. In this paper, we establishedscreening methods for asymmetric epoxidation of styrene, and optimizedthe reaction of asymmetric epoxidation of styrene by orthogonal. Basedon the asymmetric epoxidation of styrene and the screening methods, weexplored the asymmetric addition reaction of cinnamic aldehyde with1-octyne and the epoxidation reaction of addition product to expand thescope of the asymmetric epoxidation. Method: The mixture of styreneepoxidation was detected by chiral HPLC and GC-MS/SIM with internalstandard method, and the reaction conditions were optimized byorthogonal experiment. Meanwhile, the asymmetric addition of1-octyneand cinnamic aldehyde was catalyzed by BINOL/Ti(OiPr) system, and theepoxidation of its product was catalyzed by Sharpless system. Result:When analyzed by HPLC, excellent results for styrene and (R)/(S)-styreneoxide are obtained and listed as below: the correlation coefficients are0.9983,0.9996and0.9995respectively. The detection limits of styreneand (R)/(S)-styrene are respectively0.02,0.10and0.13μg/mL, recoveriesof three levels are in the range from100.2%to100.8%, and theprecisions of styrene and (R)/(S)-styrene oxides expressed in relative standard deviation are0.86%,1.52%and1.80%respectively. Whenanalyzed by GC-MS, good results are also acquired and presented asfollows: good precision (relative standard deviation are3.57%、3.08%and2.80%respectively, n=5), excellent linearity (styrene,(R)/(S)-styreneoxides are0.9997,0.9932and0.9963respectively, the detection limitsare separately1.3,1.1and0.7μg/L), reasonable recoveries(98.2%~116.1%). Asymmetric addition of cinnamic aldehyde and1-octyne has generated the chiral allyl alcohol with highenantioselectivity(up to80%) and high yield(up to70%), and epoxidationreaction of chiral allyl alcohol has produced epoxide with20%yield.Conclusion: styrene and enantiomers of styrene oxide could well beseparated by HPLC and GC-MS/SIM, and the yield and enantiomericexcess of styrene oxide could be determined. The two methods have highdegree of accuracy and precision, and could be applied to determine themixture of asymmetric epoxidation of styrene homologues and to screenepoxidation reaction. Chiral epoxy alcohols could stynthesizedsuccessfully by Sharpless epoxidation systems, but the factors ofaffecting the yield and enantiomeric excess will be further explored.