Synthesis Of Pyrazolines By Iron-catalyzed Intramolecular NN Bond Formation Reaction

Among the numerous nitrogen-containing heterocyclic compounds, pyrazoline is the important class containing the structure of ortho-nitrogen atom five-membered heterocyclic ring. Because of its characters of biocompatibility and structural diversity. Pyrazoline derivative has attracted more and more attention and has a very important value in the field of material, biology and organic synthsis.Nitrene intermediate from azide as nitrogen source to form N-N bond is very effective method to nitrogen-containing heterocyclic compounds. On one hand, nitrene can involve in a variety of reactions under moderate condition as the highly active electron-deficient intermediate. On the other hand, azide compound can be used as the ideal nitrogen source to form N-N bond. The reasons include:good processability and relatively low cost of raw materials, harmless by-products of N2, and higher atom utilization rate. In recent years, the methodological studies of azides as nitrogen source for constructing N-N bond, catalyzed by a variety of transition metal, has been reported. For example, in 2010, professor Driver reported intramolecular Fe-catalyzed N-O or N-N bond formation from aryl azide that only need 5 mol% FeBr2 as catalyst to transform azides into 2,1-benzisoxazoles or pyrazoles in high yield.This thesis explores the methodology of intramolecular Fe-catalytic N-N bond construction to transform 3-azide-N-propyl amine compounds into pyrazoline compounds. Firstly, different substituted azides with amino were synthesized by the reduction of ammoniation or nucleophilic reaction. Secondly, screening reactional condition resulted in the optimal condition:the azides (1 mmol), with FeCl3(5 mol%) as catalyst, was added to a sealing tube in anhydrous THF at 100? for 0.5 hours. Finally, we are able achieve intramolecular N-N bond formation reaction to synthesis different substitued pyrazoline compounds under the optimal condition. The reaction could be efficiently promoted by cheap catalysts FeCl3 under mild reaction conditions and has great broad functional group tolerance. At the same time, intramolecular N-N bond formation reaction of ring construction could be developed from five member ring to six member ring to produce pyridazines. This method provide an efficient synthetic strategy for the future development of intramolecular N-N bond formation reaction to generate ortho-two nitrogen heterocyclic compounds. The thesis consists of three chapters.The first chapter, introducing the important application of pyrazoline compounds; the research progress of pyrazoline compounds; chemical conversion of azide as nitrogen source and nitrene as intermediate; the brief summaries of this thesis.The second chapter, we chose an easily avaliable material of 3-azide-N-propyl benzylamine as the standard substrate to screen reactional conditions. Under the optimal reaction condition, we explored intramolecular Fe-catalyzed N-N bond construction of alkyl azide to synthesize 23 differert substituted pyrazoline compounds and 2 pyridazine compounds.The third chapter, experimental section and spectroscopic data.