The Research On The Construction Of 2-oxo-acetamidines From Methyl Ketones,Aromatic Amines And DMF Via Copper-Catalyzed C(sp~3)-H Amidination

Amidines are important structural motifs in natural products,bioactive molecules and functional materials because of their special N=C-N structure.Amidines are also valuable intermediates in organic synthesis.Therefore,direct and simple construction of amidine structures is an important and popular research area.Although considerable progress has been made in the synthesis of amidines,these methods usually use nitriles,isonitriles,organic azides,amines and amides as single nitrogen sources to construct cyclic and acyclic amidines.Most of these methods have harsh reaction conditions,unsatisfactory selectivity and provide a low overall rate of return.Amides are a key component of proteins and are widely fou nd in natural and synthetic organic molecules.Amide is also often used as a precursor molecule for the synthesis of amidine.Most amidines are synthesized from amides,and sulfonamides or polysubstituted amides are used.The method of constructing asymmet ric acyclic amidines from widely existed formamide as nitrogen source is seldom reported.It is necessary to develop a direct and effective method for the construction of asymmetric acyclic amidines from formamide.Therefore,the selective synthesis of2-oxo-acetamidine from simple small molecule materials is urgently needed.The specific research content is as follows:?1?the construction of amidines from different nitrogen sources and the synthesis of 2-oxo-amide compounds from methyl ketones and amines or amides were systematically summarized and compared.Meanwhile,the background,theoretical significance and specific experimental contents of this work were briefly introduced.?2?the coupling of methyl ketones,aromatic amines and formamides to constr uct asymmetric amidines was studied in detail.The optimal reaction conditions were obtained:acetophenone?0.5 mmol?,aniline?0.5 mmol?,CuCl ₂?20mol%?,1,10-phenanthroline monohydrate?20 mol%?,PhCOOK?1 equiv.?,di-tert-butyl peroxide?4 equiv.?,DMF?2.0 mL?,O₂?1 atm?,120 ^oC,36 h.The results showed that the reaction showed good compatibility with methyl ketones and aromatic amines with different substituents,and the target product could be obtained with medium to excellent yield.Aliphatic methyl ketones and heteraromatic amines also showed good reactivity.?3?The reaction mechanism of the coupling of methyl ketones,aromatic amines and formamides to construct asymmetric amidines was systematically studied.Through the design of control experiment,combined with the analysis of related experimental results and the report of related literature,the possible reaction mechanism of the reaction process was proposed.