| Friedel-Crafts reaction is one of the most important reactions for C-C bondformation in organic synthesis. It refers to a compound such as a halogenatedhydrocarbon, an alcohol, an olefin or an acyl halide, an acid anhydride and anelectron-rich aromatic ring or an heterocyclic ring occur electrophilic substitutionreaction, in the presence of a Lewis acid (e.g. AlCl3, FeCl3, etc.) or some proton acids. Ithas been widely used in the synthesis of aromatic compounds and heterocyclic.Based on our previous work, we develop a rapid synthesis of5,10-dihydro-pyrimido [4,5-b] quinoline through the reduction of intramolecular Friedel-Crafts reaction which occurs on the aldehyde of a pyrimidine ring and catalyzed by InCl3.Paper is divided into two sections.In the first chapter, Friedel-Crafts reactions with a carbonyl compound (aldehydeor ketone) as the alkylating or acylating agent were summarized. We also introduced thetrivalent indium salt played as a Lewis acid catalyst in such reactions. Based on ourprevious work, we also designed a series of tricyclic skeleton and summarized thebiological activity and synthetic methods of the disigned tricyclic compounds.In conventional Friedel-Crafts reaction with a carbonyl compound (aldehyde orketone) as the substrate, we should go through a two-step reaction. In recent years, somegroups have reported the use of a carbonyl compound (aldehyde or ketone) to a directstep Friedel-Crafts alkylation or acylation, which has the advantages of Simple, efficientand economical. The use of Lewis acid in Friedel-Crafts reactions has somedisadvantages such as bad catalytic selectivity, water-sensitive and difficult recovery.However trivalent indium compounds (InCl3, InBr3) have the advantages of water stability,high catalytic efficiency, and environmentally friendly. Currently, InCl3that reported has been used to catalyst Aldol reaction,1,4-addition reaction, Substitution reaction,Diels-Alder reaction, Rearrangement reaction of the epoxy compound and Friedel-Craftsreaction.The pyrimidine moiety was widely incorporated in the design of privilegedstructures in medicinal chemistry. We designed a series of tricyclic skeleton andsummarized the biological activity and synthetic methods of the disigned tricycliccompounds.In the second chapter, experimental design and synthesis work of5,10-dihydro-pyrimido [4,5-b] quinoline were introduced.4,6-dihydroxy-pyrimidine are starting materials for Vilsmeier-Hack reaction,followed by some simple substitution reactions. Then the synthesis of5,10-dihydro-pyrimido [4,5-b] quinoline through the reduction of intramolecular Friedel-Crafts reaction catalyzed by InCl3. We optimized cyclization conditions successfully andextended the range of application of the substrate. The reaction principles are asfollows:(1) The aromatic ring with electron donating groups may enhance the reactionrate.(2) Amino substituent located ortho position was prolonged on the reaction time andlower yield, compared para-position.(3) It has a certain influence on the reaction rate andthe yield when replaced by a different amino aliphatic chain.(4)The time of reaction wasprolonged when Pyrimidin-2was substituted by methylthio group. We consider that theintroduction of electron donating group to pyrimidine will reduce the electrophilicactivity of the aldehyde. It reduces the reaction rate and the time was prolonged.Cyclization products were substituted by various amines, alcohols, through Suzukicoupling, then we obtained a series of pyrimidine-fused compounds. The reactivity of6-chlorine atom is studied, which shows6-chlorine atom has a good reactivity withyield42-94%. The above results provides an efficient methodology to prepare librariesof novel5,10-dihydropyrimidine [4,5-b] quinolone. |
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