Optimization Of Chiral Epichlorohydrin Resolution Process And Its Application

Chiral epichlorohydrin is an important chiral intermediate in organic synthetic reaction.Many chiral drugs or intermediates can be synthesized in a high optical purity by usingchiral epichlorohydrin as a reagent, such as aromatic amino-propanol drugs (timolol,bisoprolol, esmolol, etc), L-carnitine, atorvastatin, radioactive sensitizers, heterocycliccompounds.(R, R)-Salen-Co (Ⅲ) catalyst was synthesized referring to Jacobsen’s report inthis paper, which was used in HKR of epichlorohydrin、styrene oxide and propylene oxide.Various factors in resolution process (reaction temperature, amount of catalyst, amount ofwater, the reaction time, the following treatment methods, etc) had been explored andoptimized.(S)-epichlorohydrin was obtained in42%yield and98%ee (determined by GCusing an Astec CHIRALDEX G-TA Capillary GC Column). The results of HKR of styreneoxide and propylene oxide consistented with the literature. The by-product (R)-3-chloro-1,2-propanediol was obtained in46%yield and was reused to prepare epichlorohydrin in ahigh recovery rate of73%. The catalyst was also recycled to be used in HKR and thecatalytic activity of the recycled catalyst wasn’t decreased after being cycled twice. And theobtained product (S)-epichlorohydrin was used to synthesize (R)-timolol in89%ee(determined by HPLC using a OD-H column).