Electrochemical Dehydrogenative N–N Bond Formation For The Synthesis Of [1,2,4]Triazolo[1,5-a]Pyridines

Triazole fused aromatic ring structure is the core skeleton of many bioactive molecules and functional materials,and triazole pyridine is one of the most important aromatic heterocyclic compounds.Among all kinds of triazolopyridine derivatives,[1,2,4]triazolopyridine skeleton widely exists in the fields of medicine,chemical industry and materials.The intramolecular N-N bond formation reaction involving transition metals or high-valent iodine reagents is one of the main methods for constructing[1,2,4]triazolo[1,5-a]pyridine compounds.However,there are some problems in these traditional methods,such as expensive metal reagents,harmful oxidants,high reaction temperature,and a large number of chemical wastes.Therefore,it is very important to develop a green,environmental friendly,cost-effective method for synthesizing[1,2,4]triazolo[1,5-a]pyridine.In the past twenty years,electrochemical synthesis has developed rapidly.As an electrically driven reaction mode,it not only has the advantages of mild reaction conditions,fast and efficient reaction,no need to add additional redox agents,but also has the advantages of good reaction selectivity.It is an environmental-friendly,atom-economical,green synthesis method that is increasingly valued by organic chemists.At present,the electrochemical synthesis of triazole heterocyclic compounds by intramolecular construction of N-N bond is relatively rare.Therefore,in order to enrich the synthetic methods of constructing triazole compounds,the development of new green and efficient electrochemical synthesis methods provides new ideas for related research.It is of great significance to develop a new method for the synthesis of[1,2,4]triazolo[1,5-a]pyridines by electrochemical intramolecular dehydrogenation.In this paper,A new method for the efficient synthesis of[1,2,4]triazolo[1,5-a]pyridine compounds by intramolecular electrochemical dehydrogenative N-N bond formation was reported.The reaction conducted at room temperature uses acetonitrile as the solvent,ⁿBu₄NBr as the redox medium and electrolyte.The target product can be obtained easily by performing the reactions under constant current electrolytic conditions in a simple undivided cell.The reaction conditions are mild,metal-and oxidant-free.All kinds of common functional groups can be tolerated,and the corresponding products can be obtained in moderate or higher yield,with the highest yield of 93%.In addition,the method can be conducted in gram scale with yield of 82%.It has potential for industrial application.At the same time,this method also can be applied for the efficient synthesis of key intermediates of anti-diabetics,and may be further applied in the subsequent drug development.