Investigation On Synthesis Of Nitrogen-containing Heterocycles Via ?-halogeno Hydrazones-Based Cycloadditions

Nitrogen-containing heterocyclic compounds are widely distributed in nature,and they are concerned by organic and medicinal chemists due to their important biological activities and unique chemical structures.Cycloaddition reaction can build a variety of nitrogen-containing heterocyclic compounds efficiently and concisely.In this paper,the novel nitrogen-containing heterocycles with potential bioactivities were synthesized by cycloaddition reactions of ?-halogeno hydrazones.The research contents are classified into the following three parts:I.Construction of 1,2,4,5-oxatriazepines via [4+3] cycloadditions of ?-halogeno hydrazones with nitronesUnder a mild condition,the novel [4+3] cycloaddition of ?-halogeno hydrazones with nitrones was developed and afforded a series of structurally diverse sevenmembered oxazepine compounds.Firstly,we used model reaction of ?-halogeno hydrazone and nitrone to optimize the reaction conditions by screening bases,solvents and base loading.Then,with the optimized reaction conditions in hand,we extended the reaction scope of the [4+3] cycloadditions by diversifying ?-halogeno hydrazones and nitrones,and obtained twenty two target products with the highest yield of 99%.Lastly,the chemical structure of the target product was unambiguously determined by single crystal X-ray analysis.According to the possible transition states obtained by DFT calculation,we proposed the reaction mechanism for the corresponding [4+3] cycloaddition reaction.II.Direct access to 1,2,3,4-tetrazines via [4+2] cycloaddition of ?-halogeno hydrazones and azodicarboxylic acid derivativesIn the presence of potassium carbonate,we established the [4+2] cycloaddition of ?-halogeno hydrazones with azodicarboxylic acid derivatives.The reaction conditions were optimized systematically by screening different factors such as inorganic bases,organic bases and solvents.Under the optimized reaction conditions,the [4+2] cycloadditions efficiently furnished structurally diverse non-aromatic 1,2,3,4-tetrazines in moderate to excellent yields(50-99% yield).The structure of the target product was determined by single crystal X-ray analysis.Moreover,we predicted the formation mechanism of 1,2,3,4-tetrazine compounds on the basis of the identified transition states by DFT calculationIII.Construction of 1,2,4-triazines via [4+2] cycloaddition of ?-halogeno hydrazones to iminesThe [4+2] cycloaddition of ?-halogeno hydrazones with imines was designed in this part.First,we screened the effects of inorganic bases,organic bases and different solvents with varied polarities on the model reaction.Next,under the optimal reaction conditions,we broadened the reaction scope of the [4+2] cycloaddition by diversifying ?-halogeno hydrazones and imines,and gained the desired 1,2,4-triazines bearing potential biological activities in moderate to good chemical yields.Last,the chemical structure of the target product was determined by single crystal X-ray analysis.And we also assumed the reaction mechanism for the [4+2] cycloaddition of ?-halogeno hydrazones with imines.