Copper Nitrate-Mediated Synthesis Of Benzo[1,2]oxazin-4-ones

Benzoxazinone is an important and ubiquitous structural unit in natural products and commercial drugs with a broad range of biological activities including antitumor,anti-bacterial,antiarrhythmia and antivirus,and plays an important role in organic synthesis.Copper salts have been widely used in organic synthesis as catalysts,mediators or oxidants,however,it is still employed at a limited level for the prompt construction of drug-like nitrogen-containing heterocycles.In this thesis,a novel copper nitrate-mediated cyclization of alkenes was developed to afford benzo[1,2]oxazin-4-ones successfully.The given approach features operational simplicity,high reaction efficiency,mild conditions and good functional group tolerance.The whole thesis contains four parts as follows:Part One: Benzoxazin-4-ones skeleton is an important structure that is found in a number of physiologically bioactive natural products and drug molecules.The recent advances of basic skeleton,biological activities and synthestic methods,for the preparation of benzoxazine-4-ones were briefly introduced.The reactions of copper nitrate as a source of nitrogen and oxygen were introduced.Finally,the research design of this thesis was present based on the preliminary works.Part Two: Several uncommercial or expensive alkenes were synthesized according to the literatures firstly.A novel and efficient copper nitrate-mediated cyclization reaction was developed from easily accessible alkenes to afford benzo[1,2]oxazin-4-ones successfully.The given method provides a new route for the synthesis of drug-like molecules.Part Three: Gram-scale reaction was conducted and the chemical transformation of the synthesized benzo[1,2]oxazin-4-one products were explored.Several nucleophilic reactions were realized efficiently as well as the radical C-H bond functionalization reaction.Part Four: Based on the documented reports and our previous results,a plausible mechanism was proposed accordingly.