Study On The Synthesis Of Imines And Nitrogen-containing Heterocyclic Compounds By TEMPO-mediated Oxidation Of Methyl CH Bond

The sp~3C-H bond widely exists in various organic compounds,and tremendous progress has been made in the research on the selective oxidative functionalization of sp~3C-H bond in recent years.Directly construct C-N bond through transition metal catalysis and redox has been successfully applied to pharmaceuticals,fine chemicals and functional materials.However,due to the high dissociation energy,inert to chemical reactions and thermodynamic stability of sp~3C-H bonds,selective activation of sp~3C-H bonds under mild conditions to construct C-N bond requires overcoming both thermodynamic and kinetic challenges.Therefore,although important progress has been made in this area in the past decades,there are still some problems for the construction of C-N bond,including harsh reaction conditions,expensive and complex catalysts,low conversion efficiency,poor selectivity and low atom economy.In view of this,the construction of C-N bond by simple and mild methods has significant importance.2,2,6,6-tetramethylpiperidin-1-oxo(TEMPO)is an air-stable tetraalkyl nitro radical,which has been widely used for the oxidation of alcohols,sulfides,metal organic compounds and as trapping reagents in radical chemistry.This paper focuses on exploring TEMPO mediated metal-free oxidation procedures for the methyl C-H bond oxidative transformation to C-N bond,realizing the synthesis of imines and N-heterocyclic compounds.The specific contents and research results are as follows:1.The methyl C-H bond cleavage of 2,6-di-tert-butyl-4-methylphenol(BHT)for the synthesis of imines and N-heterocyclic compounds.The reaction proceeds using BHT and amines as the substrates,and imines and N-heterocyclic compounds are synthesized under oxidant/TEMPO.The reaction exhibits good functional group tolerance under simple and mild reaction conditions;alkyl,alkoxy,halogen and ester substituted aromatic amines can be obtained in moderate to excellent yields.When o-aminophenol,o-aminophenol and o-phenylenediamine compounds participate in the reaction,benzoxazole,benzothiazole and benzimidazole compounds can be obtained;it provides a simple and practical method for the modification and transformation of BHT.2.TEMPO-mediated synthesis of 1H-and 2H-imidazoles from aryl methyl ketones with amines and ammonium acetate.Under weakly acidic conditions,1H-imidazoles were prepared by direct oxidation and cyclization of arylmethyl ketones and primary amines.By replacing the amines with ammonium acetate,2H-imidazole skeleton was obtained from simple and readily available aryl methyl ketones,which avoids the tedious and poorly selective prefunctionalization of substrates.A multitude of functional groups,such as alkyl,aryl,naphthalene,halogen(F,Cl,Br,I),nitro,trifluoromethyl,sulfonyl ester,furan,thiophene and pyridine,are easily transferred to the desired products.The application potential of the method is verified by the amplification synthesis of imidazole and Sonogashira coupling functionalization.The reaction makes direct use of simple and abundant starting materials,the mild reaction conditions,simple experiment procedure,and no transition metal is needed for the reaction.In view of the wide functional group tolerance,which provides a new strategy for the synthesis of 1H-and 2H-imidazoles.