Studies On The Process Of Key Intermediates Of Vitamin A And Pranlukast

The thesis focuses mainly on the process study of key intermediates of Vitamin A and Pranlukast. It consists of two Parts.In Part 1, the novel processes for producing the two key intermediates of Vitamin A-vinyl-β-ionol and (E)-4-acetoxy-2-methyl-2-butenal were developed, using commercially availableβ-ionone and isoprene as the starting materials respectively. During the synthesis of vinyl-β-ionol, the process for the preparation of Grignard reagent of vinylmagnesium chloride was further optimized, and the yield can be improved from the reported 92% to 98%. Furthermore, the amount of Grignard reagent was also reduced from the reported 1.8 equiv. to 1.3 equiv., which greatly decreased the production cost. During the preparation of (E)-4-acetoxy-2-methyl-2-butenal, two different kinds of oxidants-Urotropine and dimethyl sulfoxide (DMSO) were investigated, and DMSO proved to be the better one, improving the yield from the reported 80% to 85%.In Part 2, a practical and efficient process for the preparation of the key intermediate of Pranlukast-3-amino-2-hydrophenylethylketone was developed. Using 4-chlorophenol as the starting material,3-amino-2-hydrophenylethylketone hydrochloride can be obtained in 70% overall yield (literature yield:52%) by acetylation, Fries rearrangement, nitration, reduction and saltification. This novel process has several advantages:easy to operate, low cost and high yield, which could be applied to industrial production.