Application Of Copper-catalyzed Ullmann C-N Coupling Reaction In The Synthesis Of Benzo[e][1,2,4]Triazine Compounds

The structure of nitrogen heterocyclic ring is widely present in fields of biology, pharmaceuticals, pesticide, dyestuff and so on. Copper-catalyzed Ullmann coupling reaction is one of the most important approaches to construct C-N bond. Especially since the nineteen nineties, synthesis of compounds with the fragment of nitrogen heterocyclic ring in highly efficient, simple and convenient ways has been new hot spot of studies on Ullmann reaction with the development of catalytic system established from the combination of ligand and catalyst.Ullmann C-N coupling reaction of o-iodine amide aniline and the primary amine of hydrazide is achieved with highly chemical selectivity by using co-facilitated effect of 1H-pyrrole-2-carboxylic acid and ortho group. Then it is oxidized to azo compound under oxygen, and a following deprotection for ring-close is carried out to prepare the 1,2,4-benzotriazine compounds. The effect of variables including ligands, solvents, catalysts, bases, temperature and additives on the template reaction of N-(2-iodophenyl)butyramide and N-Boc hydrazinium has been studied, and the optimum cross-coupling condition is determined:15% 1H-pyrrole-2-carboxylic acid,5% CuI,200% K2CO3,20% NaI, DMSO, Ar,25 ℃,24 h.Then azo compound is obtained by oxidization of coupling product under oxygen. During deprotection process with trifluoroacetic acid, cyclization reaction comes out and then the substituted benzo[e][1,2,4]triazines is generated. After that, the scope of reaction is studied. And the result is satisfactory, that o-iodine amide aniline can react with hydrazide under a gentle condition. The results are all excellent whether the substrates with electron-withdrawing group or electron-donating group.