The Research On The Reaction Of Ortho-Functionalized Aryl Halides To Construct Nitrogen Heterocycle

Nitrogen-containing heterocycles as a kind of important organic small molecules,play an indispensable role in the fields of drug development,materials,life sciences and so on.Therefore,the development of efficient methods for the facile synthesis of nitrogen heterocycles is of important theoretical and practical value.Aromatic halides are a kind of common organic substrates.Due to the specific reactivity of aromatic halogen bonds,many reactions based on aromatic halides,including substitution reactions,coupling reactions and free radical reactions are gradually established.In this thesis,we envisage that using simple and readily available ortho-functional aryl halides as substrates,new synthetic methods and strategies for the synthesis of some important bioactive nitrogen heterocycles could be developed.This protocol uses nitrogen-containing small molecules and sodium azide as nitrogen source,based on the principle of self-organized reactions through integrated Ullmann couplings,nucleophilic substitutions,condensations,cyclizations,oxidations,cycloadditions,rearrangements and so on.In this thesis,five novel cascade reactions about o-halohydrazide,o-bromonitrobenzene,o-halobenzonitrile and o-halobenzald ehyde were designed,[1,2,4]triazolo[1,5-b]isoquinoline-5(1H)-one and other six nitrogen heterocycles were constructed.The main contents are as follows:In chapter 1,we firstly introduced the challenges in modern organic synthesis and the principles and significance of the self-organized reaction,and then summarized the related progress of the reactions about aryl halides in recent years.Finally,we proposed our research mentality of this thesis.In chapter 2,on the basis of copper-catalyzed Ullmann coupling,a highly efficient three-component domino protocol has been developed for the synthesis of[1,2,4]triazolo[1,5-b]isoquinolin-5(1H)-ones from simple and readily available o-halogenated benzohydrazides,aldehydes and nitriles.This domino process involves sequential condensation,copper-catalyzed intermolecular C-arylation and bicyclization.In chapter 3,we have developed a highly efficient domino protocol for the rapid synthesis of 5-phenyl-[1,2,3]triazolo[1,5-c]quinazo lines derivatives from simple and readily available(E)-1-bromo-2-(2-nitrovinyl)benzenes,aldehydes,and sodiunm azide.This elegant domino process integrated consecutive[3+2]cycloaddition,copper-catalyzed SNAr,reduction,cyclization,and oxidation sequences.Notably,sodium azide acted as a dual nitrogen source in the construction of this novel fused N-heterocycle.In chapter 4,on the basis of the previous chapter,A highly efficient Fe/Cu relay-catalyzed domino protocol has been developed for the synthesis of 2-phenyl-quinazolin-4-amines from commercially available ortho-halogenated benzonitriles,aldehydes,and sodium azide.This elegant domino process involved consecutive iron-mediated[3+2]cycloaddition,copper-catalyzed SNAr,reduction,cyclization,oxidation,and copper-catalyzed denitrogenation sequences.More importantly,this novel Fe/Cu relay catalyzed cascade strategy lprovides a concise patlhway for the synthesis of a kind of human adenosine A3 receptor inhibitor.In chapter 5,an benzannulation reaction has been realized by integrating intermolecular adol condensation with subsequent intramolercular base-promoted homolytic aromatic substitution.This novel cascade reaction provides a straightforward approach toward various naphtho-fused oxindoles from 2-halobenzaldehydes and indolin-2-ones.The biggest highlight of this reaction is the dual role of indolin-2-ones.In the presence of base,indolin-2-ones would be deprotonated to afford electron-rich enolates,most of which would condense with 2-halobenzaldehydes,and the rest would serve as electron donor to promote the following intramolecular C-H arylation.In chapter 6,a synergetic tent-butyl hydroperoxide/K3PO4-promoted oxidative cyclization has been developed for the facile synthesis of various functionalized quinazolin-4(3H)-ones from commercially available isatins and amidine hydrochlorides at room temperature The synthetic utility of this strategy was illustrated by the convenient synthesis of tryptanthrin derivatives via a self-dimerization of isatins in the absence of amidine hydrochlorides under the same conditions.In chapter 7,the summary of this thesis and the outlook of future work were given.