Application Of Carbon-nitrogen Coupling Reaction In The Synthesis Of Hydrazine

Organic nitrogen-containing compounds（ie organic compounds containing C-N bonds in the molecule）are important compounds in organic synthesis.They not only widely present in various pesticides, medicines,dyes,but also are an important part of many natural products and functional materials. Inclouding,substances that necessary for life activities,such as macromolecular heterocyclic Porphyrin,are important component of chlorophyll and heme.Therefore,the construction of new C-N bonds based on the existing simple compounds is very important for the synthesis of nitrogen-containing compounds. Researchs in this field haves always been hot spot in organic synthesis.The Buchwald-Hartwing reaction catalyzed by palladium,the Ullmann reaction catalyzed by copper,and the Chan-Evans-Lam reaction are all been used to build C-N bonds and synthese the nitrogen-containing compounds.They all are classic method for C-N bond construction.This thesis is fixed on the Buchwald-Hartwing and Chan-Evans-Lam reactions for the related exploration and research.Aryl hydrazone and aryl hydrazine both are important intermediates in organic synthesis.They been widely used in the synthesis of some nitrogen-containing heterocycles which are biologically active molecules,including indole,indazole,pyrazole,triazole and so on.The traditional method to prepare aryl hydrazine typically with harsh reaction conditions,poor functional group tolerance,and a large amount of waste salts.More importantly,the direct preparation of hydrazine compounds is toxic.Our work is to use benzophenone hydrazone to couple with chloroarene or arylboronic acid to form aryl hydrazone,and then hydrolyze aryl hydrazone to obtain arylhydrazine,which provides an indirect way to obtain arylhydrazine.Using benzophenone hydrazone as a nucleophile can react well with chlorobenzene,in the Buchwald-Hartwing reaction system catalyzed by Pd（OAc）₂.The optimal conditions are as follows:0.5mol%of Pd（OAc）₂ as the catalyst,and 1 mol%of 2-（di-tert-butylphosphine）-2’-（N,N-dimethylamino）biphenyl as ligand,1.4 equiv NaOH,tert-butanol as solvent,and reacted at 90°C for 5 hours.The model reaction obtained a 87%yield.The system can be applied to the reaction of chlorobenzene with different substituted benzophenone hydrazone.The functional group is well tolerated,and the naphthalene ring structure can also achieve high yield.This work provides an effective way for the synthesis of hydrazines and their derivatives.On the basis of the previous work,the reaction of arylboronic acid with benzophenone hydrazone as the nucleophile was further studied.The C-N coupling reaction of aryl boronic acid and benzophenone hydrazone was achieved under the Chan-Evans-Lam reaction system.The optimal reaction conditions were:1.5 equiv Cu（OAc）₂,10 mol%ligand,2.0 eq pyridine N-O compound,dichloromethane as the solvent,and the reaction was performed at room temperature for 24 hours.The yield of the model reaction was 80%.Unfortunately,the applicability of the reaction is not very good,only 8 substrates have been expanded,with the yield is between 42%-80%.Based on the work in the previous works,we further realizes the selective coupling of arylboronic acid with 3-indazolidone,and prepared a series of monoaryl substituted and diaryl substituted indazole derivatives.The optimal conditions for monoaryl substitution are as follows:20 mol%Cu（OAc）₂,1.0 equiv Pyridine,1.0 equiv Benzoyl peroxide,DCM as the solvent,and the reaction at room temperature for 24 hours.The yield of the model reaction is 80%.The optimal reaction conditions for bisaryl substitution:20mol%Cu（OAc）₂,2.5 equiv K₂CO₃,DMSO as the solvent,performed at room temperature for 24 hours,and the yield of the model reaction was 81%.