Study On The Cross-dehydrogenative Coupling Reaction Of Pyridone And The Nitrification Of Isatin

This thesis is divided into the following two parts:（1）Research on the cross-dehydrogenative coupling reaction of pyridone and acrylate;（2）Research on the nitration reaction of isatin.The first part is the study of the cross-dehydrogenative coupling reaction of pyridone.Pyridone structures are widely present in natural products and pharmaceutical active molecules.Many compounds containing pyridone structures have good biological activity and application prospects.In addition,the formation of carbon-carbon bonds is the focus and hotspot of organic synthesis reactions,and it is also one of the main ways to construct complex molecules.Coupling reactions catalyzed by transition metals have received extensive attention due to their high reaction efficiency and strong regioselectivity.Among them,the cross dehydrogenative coupling reaction（CDC）forms various oxidation intermediates in situ by adding transition metals and oxidants,which can realize the construction of carbon-carbon bonds,which is convenient,fast and efficient.In this paper,the cross-dehydrogenative coupling reaction of2-pyridone and acrylate was realized for the first time.The reaction is catalyzed by Pd（OAc）₂,AgTFA is used as the oxidant,and1,2-dichloroethane is used as the solvent.The cross-dehydrogenative coupling reaction of 2-pyridone and acrylate,which is cheap and easy to obtain,is obtained.Series of 3-pyridin-2-oxy acrylates with various substituents,the reaction yield is as high as 79%.This reaction has the advantages of good substrate adaptability,mild conditions and easy operation.This method provides new ideas for the synthesis of pharmaceutical intermediates and natural products in the future.The second part is the research on the nitration reaction of isatin.Indole derivatives have received extensive attention due to their special pharmacological activities.Isatin（indole-2,3-dione）is one of the simplest indole derivatives and is a leading compound with pharmacological activity in drug design"Priority Skeleton".For example,indigo can be used to treat granulocytic leukemia and is the active ingredient in the traditional Chinese medicine Danggui Longhui Pill;indirubin derivatives can inhibit signal transduction and activator of transcription 3（Stat3）signal transduction and induce cell apoptosis The expression in human cancer cells has an anti-proliferative effect on human cancer cells by inhibiting genes or proteins that regulate cell cycle progression.This article developed a new method of isatin nitrification.By using trifluoroacetic acid as the reaction solvent,silver nitrate as the nitration reagent,and easy-to-prepare nitrogen-methyl-protected isatin and its derivatives as raw materials,a series of various substituted 5-position or7-position nitration products were obtained..The reaction yield is as high as 94%,and it has the advantages of mild conditions,good regioselectivity,and rapid reaction.