Research On Palladium-Catalyzed Alkynyl Cyclization For The Synthesis Of Nitrogen-Containing Compounds

Nitrogen-containing compounds are an important kind of organic compounds which are widely found in animals,plants and natural products.Many biologically active macromolecules or compounds with potential medical value are nitrogen-containing compounds.Therefore it is widely used in many fields such as medicine,fuel,dyes,materials and food additives.In recent years,with the continuous development and progress of science and technology,more and more nitrogen-containing compounds with novel structures and unique properties have been synthesized,which greatly facilitates people’s production and life.Thus,the synthesis of nitrogen-containing compounds has become one of the hotspots and focuses in the field of organic synthesis.This thesis focused on the synthetic methodology of palladium-catalyzed synthesis of nitrogen-containing compounds.The thesis was divided into four parts:The first part systematically reviewed the research progress of palladium-catalyzed cyclization of alkyne to synthesize nitrogen-containing compounds.In the second part,a new method of palladium-catalyzed oxidative hydrolysis of 2-alkynylaryl azide to 2-benzamide benzoic acid was obtained.The synthesis method had many advantages such as short reaction time,mild reaction conditions and high yield.After a series of optimization experiments,the optimal reaction conditions were obtained then the substrate expansion was carried out under the optimal conditions.The results shown that 2-alkynylaryl azides with different substituents can perform the reaction well.Through the reaction mechanism verification test,the reaction mechanism was confirmed that 2-alkynylaryl azide first oxidized to 2-phenyl-3H-indol-3-one,then the Baeyer-Villiger oxidation rearrangement was happened to obtained 2-phenyl-4H-benzo[d][1,3]oxazin-4-one,finally the 2-phenyl-4H-benzo[d][1,3]oxazin-4-one hydrolyzed to obtain the target product.In the third part,a method for synthesizing 3-halogenindole by palladium-catalyzed reaction of 2-alkynylaryl azide with hydrohalic acid in the aqueous phase was obtained.The synthesis method was green and environmentally friendly under mild reaction conditions.The raw material sources were wide and the products was got under high yield.The substrate expansion was carried out under the optimal reaction conditions which confirmed that the 2-alkynylaryl azide with different substituents can be carried out.Combined with the previous research results of our research group,the reaction mechanism is speculated as follows: The α-imine palladium carbene was formed under the action of palladium-catalyzed 2-alkynylaryl azide and attacked by hydrohalic acid.Then the corresponding 3-halogenindole was obtained after catalyst released.In the fourth part,a method for synthesizing 3,3-dichloro-2-phenyl-3H-indole by palladium-catalyzed transformation 2-alkynylaryl azide was obtained.The reaction mechanism is that 2-alkynyl aryl azide reacts with hydrohalic acid to produce 3-chloroindole then reacted with N-chlorosuccinimide under alkaline conditions to got 3,3-dichloro-2-phenyl-3H-indole.The synthetic method was simple and efficient under mild reaction conditions,which provided t he desired product in up to 90% yield.