Study On Synthesis Of ?-Oxo-acetamidine By Aromatic Methyl Ketone And Amine Compounds

The transition metal-catalyzed transformation of C-H bond to construct carbon-carbon bonds,and carbon-heteroatom bonds has always attached the attention of chemical researchers.In recent years,the construction of C-N bonds from C-H bonds,such as the amination and amidation of C-H bond,has been extensively studied and developed.However,the amidination of the C-H bond is rarely studied.Amidines and its derivatives are a class of compounds with N-C=N structure,which are commonly found in natural products and biologically active molecules.Amidines and its derivatives are widely used in the fields of pharmaceutical chemistry,organic synthesis intermediates,catalyst design,materials science,supramolecular chemistry and ligand chemistry.The classic synthesis methods of amidines include amide acetal method,amide method,nitrile amine method and the original formic acid ester method,etc.,in which the reaction conditions are harsh,long reaction time and other shortcomings.Transition metal-catalyzed midination of C-H bonds in line with green environmental protection,economic savings and other requirements,so the development of a transition metal-catalyzed amidination method is highly desired.In this paper,we used copper as a catalyst,with aromatic methyl ketone and amine as-substrates in the oxygen atmosphere,and successfully synthesized a series of amidinates.The main research contents are as follows:(1)The research progress of different types of amidines and its derivatives is briefly reviewed,and the main contents and significance of this thesis are expounded emphatically.(2)The reaction between aromatic methyl ketone and amine to synthesize ?-oxoacetamidine was studied systematically.Firstly,the reaction conditions such as catalyst,catalyst dosage,base type,solvent,different environment atmosphere,reaction temperature,reaction time and solvent were screened.The optimum reaction conditions were confirmed:acetophenone(0.5 mmol),aniline(1.1 mmol),CuCl2(20 mol%),PhCOONa(0.5 equiv.),Dimethyl sulfoxide(1.0 mL),80?,30 h,oxygen(1 atm).Under the optimum reaction conditions,First,we examine the reaction of different types of aromatic methyl ketone with aniline,The results showed that aromatic methyl ketones possessing electron-withdrawing or electron-donating functional groups reacted with aniline in higher yields.Subsequently,we investigated the reaction beween acetophenone and a series of substituted anilines.This approach displays good functional group compatibility.Finally,we synthesized unsymmetrical amidines via multicomponent reaction(MCRs)with acetophenone,aniline and secondary or primary amines as substrates under optimal reaction conditions The approach has the characteristics of easy available raw materials,convenient operation,mild reaction conditions and wide substrate scope.(3)The mechanism in the copper-catalyzed aerobic amidatiation of aromatic methyl ketone and amine to ?-oxoacetamidine was finally investigated.In view of the experimental results in this approach,and combined with the results of control experimental design and relative literature on synthesis of a-oxoacetamidines,we propsed the possible reaction mechanism,in which acetophenone was oxdized to the key intermediate phenylglyoxal,then phenylglyoxal reacted with aniline to produce imine,followed by nucleophilic reaction with aniline to give the title compound.