Study On The Construction Of Nitrogen-containing Heterocyclic Rings Under Electrochemical Conditions

As a novel synthetical technology,organic chemical synthesis method is a process of organic synthesis using electrochemical methods.Through the"electrode-solution"interface,organic molecules or catalytic media can achieve charge transfer,realizing the conversion between electrical energy and chemical energy and enabling old bonds’cleavage and new bonds’formation.Compared with the traditional organic synthetical methods,as an effective green chemical method,electrochemical synthesis technology reduces the use of metal catalysts,oxidants and other additives,thus avoiding the generation of by-products in the reaction process.Heterocyclic skeletons are the core structure of many natural products and drug molecules.Among these,nitrogen-containing heterocyclic compounds are an important part of heterocyclic compounds,with high biological activity and pharmacological activity,which play an important role in the fields of chemistry,biology,and medicine.Therefore,exploring a novel,efficient and environmentally friendly method of synthesizing aza-heterocyclic derivatives has always been a hot topic in organic chemistry.The main research content of this thesis is to achieve the synthesis of nitrogen-containing heterocyclic compounds（quinazolinone and isoxazole compounds）by electrochemical methods.The specific content is as follows:（1）Quinazolinone compounds are important structures of a variety of alkaloids and have special physiological activities.In this thesis,a reaction for the synthesis of dihydroquinazolinones using electrochemical methods was designed,wherein methanol is activated and used as a C1 source.The cyclization of methanol with 2-aminobenzamide could be carried out without any homogeneous metal catalyst,external oxidants,or bases.The optimal conditions are as follows:Glass carbon electrode（GCE）as the anode,platinum electrode（Pt）as the cathode,tetraethyl ammonium hexafluorophosphate（Et₄NPF₆）as the electrolyte,methanol（Me OH）and hexafluoroisopropanol（HFIP）as the solvent（Me OH is also used as the starting material for the reaction）,the current was set as 5 m A,and the reaction was stirred at room temperature under air conditions for 16 h.The target product N,N’-dihydroquinazolinone could be obtained in 97%yield.Under optimal reaction conditions,22 products were isolated in moderate to good yields,and the final structures of the obtained compounds were determined by nuclear magnetic resonance and high-resolution mass spectrometry.In addition,when deuterated methanol was used,the deuterated methylene was incorporated into the nitrogen-containing heterocyclic rings,providing an efficient pathway for obtaining deuterated N-heterocyclic rings.（2）As a cheap and non-toxic chemical reagent,ethylene glycol（EG）is a good reagent that constitutes the skeleton of methyl,methylene,and carbonyl groups.Using ethylene glycol as the C1 source,dihydroquinazolinone could be also obtained under electrochemical conditions.With the glass carbon electrode as the anode,the platinum electrode as the cathode,ethylene glycol and hexafluoroisopropanol as the mixed solvent,and tetraethyl ammonium hexafluorophosphate as the electrolyte,the setting current as 5m A,N’,N-disubstituted dihydroquinazolinone could be obtained in 98%yield after 16 hours’reaction.Furthermore,32 products were separated in good yields,with broader substrate scope and better isolated yields.（3）Isoxazole compounds are five-membered heterocyclic compounds containing adjacent N and O atoms,which are widely used in organic synthesis.Using electrochemical technology,to avoid the use of oxidants,metal catalysts and other additives,benzaldehyde oxime and ethyl propionate could be converted to isoxazole compounds directly.Herein,platinum tablets were used as both anode and cathode,Bu₄NBr as the electrolyte,trifluoroethanol as the solvent.The isoxazole compound could be isolated in 90%yield after6 hours’stirring.