Electrochemical Oxidation For The Construction Of Csp~2-Br/Csp~2-N Bonds

The construction of carbon hetero bonds is an extremely important reaction in the field of organic synthesis,which is widely used in the preparation of drug intermediates and in the total synthesis of natural products.The traditional methods to form carbon hetero bonds are mainly catalyzed by transition metals with ligands,strong bases or high boiling point solvents.Electrochemical synthesis is characterized by environmentally friendly,highly efficient and is also recognized as an important method for constructing challenging carbon heteroatom bonds.Therefore,based on our continued interest in electroorganic synthesis,this paper proposes the methods for constructing Csp~2-Br/Csp~2-N bonds under electrochemical conditions.The paper mainly includes the following two parts:First,based on a review of the electrochemical construction of aryl carbon-halide bonds and an analysis of the halogenation of imidazo[1,2-a]pyridine,a one-pot electrochemical synthesis of 3-bromoimidazo[1,2-a]pyridine was designed.Using 2-aminopyridine and2-bromoacetophenone as substrates,the reaction conditions of electrochemical synthesis of3-bromoimidazo[1,2-a]pyridine were optimized,such as solvent and current.The addition of chemical oxidant and acid or base additive,etc,was not necessary for this new method.The scope of this reaction was broad,and the substrates with either an electron-withdrawing group or an electron-donating group on the aryl ring could be transformed in good yields(46%-92%).In addition,after the studies of control experiments and CV,a possible mechanism had been proposed.Finally,the gram-scale reaction and the synthetic application of the product were carried out,which further showed the application prospect of the method.The second part of the work is to synthesize acetaminophen compounds by electrochemical direct oxidation of phenol to form Csp~2-N bond with acetonitrile.With the review of the electrochemical construction of Csp~2-N bonds in the past few years,and the previous synthesis of acetaminophen,we have envisioned a strategy for the synthesis of paracetamol compounds in one step using phenols and acetonitrile.In this thesis,a series of optimization were carried out by using 2,6-dimethylphenol as substrate through the control variable method,and finally N-(4-hydroxy-3,5-dimethylphenyl)acetamide was obtained in a73%yield.Further researches on substrate scope and mechanism are undergoing in our group.