Study On The Synthesis Of Aminopyridine And Imidazo[4,5-b]pyridine From Halopyridines And Amidines

Nitrogen-containing heterocyclic compounds is the largest class of organic compounds in heterocyclic compound,which play an extremely important role in the fields of chemistry,function materials and medicine intermediate development,and the construction of C-N bonds.It is of great significance to employ cheap and available amidine salt as a nitrogen source to achieve C-N bond coupling in virtue of nucleophilic substitution reaction.In the first chapter,we present recent literature about the strategies and the state of art in construction of C-N bonds.According to the synthetic protocols of C-N bond construction,the reported work could be classified into cross coupling,C-H bond activation,and other synthetic methods.Among them,cross-coupling and C-H activation are the main access to form C-N bonds.Based on the previous literature review,we describe the research purpose,significance and research content of the topic.In the second chapter,we introduce a new method for the synthesis of 2-aminopyridine compounds through amination process of pyridyl halides derivatives.In the presence of strong base,2-fluoropyridine compound was added to cheap and easily available acetamidine hydrochloride to obtain corresponding 2-aminopyridine derivatives,via nucleophilic amination and hydrolysis reaction,with good functional group tolerance and high yields.It is worth mentioning that the amination reaction can occur without need of transition metal catalysts and expensive ligands,which thus could avoid environmental pollution and be confirmed to the principle of green chemistry.Moreover,the synthetic strategy is simple,clean and suitable in industrial application.In the third chapter,we discuss the synthesis of pyridylamide compounds and imidazo [4,5-b]pyridine compounds derivated from halopyridine and amidine salt starting materials.In the absence of metal catalyst,N-(pyridin-2-yl)acetamide can be obtained from dihalopyridine and amidine salts via C-N coupling reaction.In the presence of copper(I)iodide catalyst,nucleophilic cyclization occurred between dihalopyridine and amidine salts which gave target molecule 3H-imidazo[4,5-b]pyridine and 1H-imidazo[4,5-b]pyridine,through “one-pot” two-step-process.The strategy has some advantages such as good to excellent yield,simple operation and high chemselectivity.