Research On Denitrogenation/cyclization And Functionalized Reaction From α-Azido Ketones

α-Azido ketones is a kind of organic azide compounds with good activity,which can be used to construct various nitrogen-containing heterocyclic compounds.Our research group has been devoted to the study of various organic synthesis reactions withα-azido ketones as the substrate,that is,firstly,the appropriate catalyst is selected to realize the in-situ effective denitrogenation ofα-azido ketones,and then the corresponding intermediates are generated,which are captured by various reagents,and finally a series of nitrogen heterocyclic compounds are obtained.Based on this,α-azido ketones was used as the substrate to try to combine denitrogenation with cycloaddition or oxidation to synthesize quinazoline,ketoamide and other target molecules under the best conditions in this paper.In addition,we also tried to use easily available acetophenone as substrate to make it undergo functionalization reaction,and then synthesize ketoamide compounds.In a word,it is expected to provide a new simple and effective strategy for the synthesis of bioactive molecules.This paper mainly includes the following five chapters:In chapter 1,the preparation ofα-azido ketones and its research progress in organic synthesis were investigated and summarized.It is known that the three sites ofα-azido ketones have high reactivity,which can not only react independently,but also react at two or more sites at the same time to construct nitrogen heterocyclic compounds with complex structures.Based on this,this chapter mainly describes the different reactions ofα-azido ketones in different positions.In chapter 2,on the basis of investigating the related literature on the synthesis of quinazoline derivatives and the literature in chapter 1,we proposed a simple strategy for the synthesis of quinazoline compounds via Rh（III）catalyzed tandem reaction usingα-azido ketones and 2,1-benzisoxazoles as substrates.The reaction has the advantages of easily available substrates,simple operation,excellent yields,good tolerance of functional groups and easy gram-scale synthesis.In chapter 3,on the basis of investigating the related literature on the synthesis ofα-ketoamide compounds,we reported a copper（II）promoted denitrogenation and oxidation for the preparation of primaryα-ketoamides using simple and easily availableα-azido ketones as a single substrate and TEMPO as an oxidant.This method not only has short reaction time,simple operation and high yield,but also has strong tolerance of functional groups.Furthermore,gram-scale synthesis experiments have been completed.In chapter 4,although many methods for preparingα-ketoamides have been developed in recent years,there are still some shortcomings,which may be that the substrate is not easy to obtain,the reaction conditions are harsh,or the functional groups are not well tolerated.In view of the good physiological and pharmacological activities ofα-ketoamide compounds,it is a great research significance to develop a simple substrate,mild conditions and no transition metal catalysis reaction to synthesize these compounds.In addition,by investigating the related literature on the synthesis ofα-ketoamide compounds,we know that most methods for preparingα-ketoamide from acetophenone have the advantages of low cost,easy availability,simple operation and high atomic economy.Therefore,we designed a simple method to synthesize primaryα-ketoamides via I₂ mediated oxidative amidation using easily available acetophenone as substrate and ammonium carbamodithioate as amine surrogate.This method does not need transition metal catalysis,and the reaction conditions are mild.In chapter 5,the content of this master’s thesis is summarized,and the future work is discussed and prospected.