Alkylation Of 1,2,3-triazoles On The Nitrogen Atom

Since the copper-catalysed alkyne-azide click reaction has been proposed,1,2,3-triazoles have received considerable attention and were widely used in medical chemistry,materials chemistry,synthetic organic chemistry and other fields application.Most 1,2,3-triazoles are obtained by the reactions of organic azides with other reactants such as click reactions with an alkyne,multi-component reactions with activated carbonyl compounds,and condensation reactions with activated olefins.Later,other azide-free strategies were also proposed.These methods typically produce N¹ or N^1’-substituted 1,2,3-triazoles.On the other hand,the post-N-functionalization of NH-1,2,3-triazole is also an alternative strategy for the synthesis of diverse1,2,3-triazoles and,more importantly,it is also an important approach to synthesize N²-substituted 1,2,3-triazoles.The reactants in this type of reaction may be halogenated alkanes,alcohols,alkynes and alkenes.At the same time,cross-dehydrogenation coupling（CDC）reactions have become powerful tools for organic synthesis due to the high atomic and step economy.Recently,there have been cases of synthesizingN-substituted heterocyclesusing cross-oxidative dehydrogenation coupling reactions.However,as mentioned above,the synthesis of N¹-substituted 1,2,3-triazoles was mature at present and the synthesis of N²-substituted 1,2,3-triazoles was relatively rare,and alkylation and arylation of NH-1,2,3-triazoles are the major ones.In this paper,we first use 4-phenyl-NH-1,2,3-triazole as raw material,DMF as solvent and reactants,potassium peroxodisulfate as oxidant,copper acetate as catalyst,and sodium carbonate as base,under these conditions alkanoylation products was genarated in high conversion yields,but there are two isomers because of the different nitrogen substitution positions;On this basis,in order to improve the selectivity of the reaction,wechosetouse4-methyl-5-phenyl-NH-1,2,3-triazoleand4-bromo-5-phenyl-NH-1,2,3-triazole as starting materials to improve the regioselectivity of nitrogen functionalization through the introduction of the steric hindrance.We then demonstrated and explained the regioselectivity of this reaction from the related literatures and NMR spectros;Finally,in order to improve the yield of the reaction of 4-phenyl-NH-1,2,3-triazole,we also refered to the relevant literature to give a multi-step,high total yield scheme.