Palladium-catalyzed Synthesis Of Polysubstituted Quinolines From 2-amino Aromatic Ketones And Alkynes

Quinoline and its derivatives are a class of special structure and properties of aromatic heterocyclic compounds, which have been widely used in the field of medicinal chemistry, synthetic chemistry, materials chemistry, biochemistry, etc.Therefore exploring simple, economical, and environmentally friendly synthesis methods to construct this kind of compounds has important scientific significance and potential application value. Although there’re numerous methods of synthesis of quinolines, all the reported methods generally require stringent reaction conditions and tedious experimental procedures or produce a lot of waste, cause serious pollution to the environment. In this paper, we developed an one-step method for the synthesis of multi-substituted quinoline, which used palladium as the catalyst, 2-amino aromatic ketone and alkynes as the starting material. This method is convenient with cheap raw materials, and has good adaptability to the substrate. In addition, the whole reaction process of removing only one water molecule, which consistent with the guiding ideology of sustainable development of modern chemistry.The main research work of this paper includes the following parts:Firstly, the exploring of the synthesis of 2,3,4-triphenyl quinoline with 2-amino benzophenone and diphenyl acetylene as the start material. Through a series of condition optimization(change catalyst, ligand, solvent, additive, temperature ect.),and ultimately determine the optimal conditions were as follows: 5 mol% Pd Br2 as catalyst, 8 equivalent of Piv OH as additive, DCE and benzonitrile(1:1) mixture as solvent, 130 o C stirs 18 hours. The target product 2,3,4-triphenyl quinoline was obtained in 83% of separation yield.Secondly, the exploring of the reaction substrate and reaction mechanism under the optimal reaction conditions. With the different substituted 2-amino aryl ketone and acetylene as raw material under the optimum reaction conditions to test the substrates of applicability and functional group compatibility. Experiments show that this method has wide range of substrates and the functional group compatibility, provides a convenient way for the synthesis of 2,3,4-substituted quinoline.Finally, the preliminary study on reaction mechanismIn conclusion, through the design, we developed a new method of synthesis of quinoline with the reaction of broad substrate scope and good functional groupcompatibility. The study of certain innovation could provides experimental and theoretical basis for the research and development of other quinoline derivatives.