Studies On PIDA Oxidative Direct And Selective Functionalization Of Quinolineamides At The 5-Position

In this paper, we introduced the research of functionalization of quinolineamides at the 5-position trifluoromethylation and halogenations in the synthesis. The method of PIDA oxidative direct and selective functionalization of quinolineamide derivatives at the 5-Position was reasarched, introducing the trifluoromethylation and halogenations group. The article is divided into four chapters:Chapter one: giving a brief introduction on development of functionalization of quinoline at the 5-positionThe broad distribution of quinoline scaffolds in bioactive molecules and natural products has spurred considerable efforts toward the development of efficient strategies to the functionalization of these appealing structural motifs. Successful examples in the field typically focus on the transformation of C-H bonds at the C-2, C-3, and C-8 positions of quinolines. In contrast, efficient approaches to the C-5 functionalization of quinolines are still rare.Chapter two: Reviewing the recent studies about trifluoromethyl reactions.Many modern pharmaceuticals contain fluorine atoms because fluorinated organic compounds have enhanced lipophilicity and membrane permeability, elevated electronegativity and oxidation resistance. Therefore, the trifluoromethylated molecules are becoming increasingly important in potential application. In recent years, new trifluoromethylation reagents have been developed, which have been applied to achieveing trifluoromethylation of olefins, aromatic and heterocyclic compounds.Chapter three: Studies on PIDA oxidative direct and selective trifluoromethylation of quinolineamide derivatives at the 5-PositionGiving an account of the investigation PIDA oxidative trifluoromethylation of quinolineamides at the 5-Position. Then the reaction conditions were optimized, the substrate scopes of trifluoromethylation with different aminoquinolines were investigated, a plausible mechanism is proposed, Gram-scale trifluoromethylation of quinolineamides were obtained.In the presence of PIDA as the oxidant, NH2SO3 H as the additive in DCE, quinolineamides react with NaSO2CF3. In the intermolecular, sp2C-H(quinoline) bond activation was supplied successively to form C-CF3 bond, which generated the C-5 trifluoromethylated quinolineamides. As a result, this reaction can be compatible with a large number of functional groups.Chapter four: Studies on PIDA oxidative direct and selective halogenations of quinolineamide derivatives at the 5-PositionWe have developed a efficient method of PIDA oxidative halogenation of quinolineamides at the 5-Position. Then the reaction conditions were optimized, and the reaction substrates were expanded. These reaction proceed under mild condition and obtain high applicability and good yields. The product was characterized, by X-ray single crystal diffraction, nuclear magnetic resonance(NMR), high resolution mass spectrometry and melting point instrument examination to determine the correctness of the structure.