Ⅰ. Research On One-step Conversion Of Acetophenones To α-Haloacetophen-one Dimethyl AcetalsⅡ. Synthesis Of Derivatives Of The Lignans Hydroxyotobain

The first part of this paper relates to the research on the synthesis of a-haloacetophenone dimethyl acetals by one-step.a-haloacetophenone dimethyl acetals are a kind of important synthetic intermediates which were widely used in the fields of pharmacy, pesticides, perfume, etc. Traditionally two steps is needed if we want to prepare a-haloacetophenone dimethyl acetals:(1) firstly, substituented acetophenone were converted to a-haloacetophenones, the conventional halo-agents including bromine(Br2), N-bromosuccinirmide(NBS), N-chorosuccinimide(NCS), N-bromoacetamide(NBA), N-chloroacetamide(NCA),1,3-dichoro-5,5-dimethylhydantoin(DCDMH),1,3-dibro mo-5,5-dimethylhydantoin (DBDMH);(2) a-haloacetophenones reacted with methol or trimethyl orthoformate catalysed by acid to prepare a-haloacetophenone dimethyl acetals. But this reaction was an equilibrium reaction, so hexane, benzene or other water-removing agents was added which was beneficial to the generation of acetals. In spite, the yield of acetals was not very good.During our research73%a-chloro-4-nitroacetophenone dimethyl acetals was found as by-product when4-nitroacetophenone was reacted with DCDMH in methol catalysed by SiO2. On this basis, after explored the best catalyst, the mount of catalyst and other factors, we developed a method which could prepare a-haloacetophenone dimethyl acetals by one-step. When substituented acetophenone reacted with DCDMH catalysed by4A molecular sieve and piperidine under refluxing12h in anhydrous methol, a-chloroacetophenone dimethyl acetals were obtained by50%～100%. As to the substrates with electron-withdrawing groups, the conversions were relatively high. Similarly, when substituented acetophenone reacted with DBDMH catalysed by4A molecular sieve and piperidine under50℃-52℃, a-bromoacetophenone dimethyl acetals also could be obtained by50%-100%. We think this is a good method for preparing a-haloacetophenone dimethyl acetals which could be applied to organic syntheses. In addition,1,3-chloro(dibromo)-5,5- dimethylhydantoin(DCDMH/DBDMH) were a kind of disinfectant which were available, cheap and harmfulless. They have lots of advantages such as environment-friendly, simple operation which were used as halo agent and acetal agent.The second part of this paper relates to synthesis of derivatives of the lignans HydroxyotobainNatural drugs is one important part of drugs. So far, a number of bioactive drugs were extracted from animals, plants, microbes, halobios and other natural resources. But some natural drugs could not be clinical drugs because poor bioavailability, high toxicity or other drawbacks. So natural drugs had to modified the structure in order to develop efficient, high bioavailability and low toxicity drugs. This is also the "shortcuts" to develop new drugs. Myristica fragrans Houtt is a large and evergreen wood which was edible and medical. Some extractions from its fruit and bark have much medical value. Hydroxyotobain was one kind of lignans extracted from the bark of Myristica Fragrans Houtt and biological test suggested that it had some anticancer activity. In order to research the relation between structure and bioactivity, Xu Zijing prepared four terminal compounds Didehydro-otobain(otobaene), Methoxyotobain, Benzyloxyotobain, Allyloxyotobain from the Hydroxyotobain as the raw material. And for the sake of further research between structure and bioactivity, we designed two Hydroxyotobain derivatives. In the end, we smoothly get the key intermediate of two derivatives by Bromination, Demethylation, methylenation, carbonyl protection, nucleophilic addition, oxidation from2-bromo-3-hydroxy-4-methoxybenzaldehyde as the raw material.