Catalytic Synthesis Of Amides And N-alkyl Amides By Hydration Of Nitriles

As a prevalent and essential linkages for pharmaceutical intermediates,amides were widely used in many pharmaceuticals and chemical industry.The amide bond(-CO-NH-)plays an irreplaceable role in polypeptide compound.The N-alkylamides are important organic compounds containing amide bond.They are widely present in natural products,pharmaceuticals,fine chemical products,polymers and polymer materials.At present,the reported methods of amides' synthesis usually existed some disadvantages:required large quantity of catalyst;using toxic organic solvents;needed excessive alkali;limited substrate scope;harsh reaction conditions etc.In this paper,we used metal catalyst[Cp*Rh(H20)3](OTf)2 to synthesize amides via hydration of nitriles by using acetaldehyde oxime as the water source.Then,we expanded the scope of the reaction substrates.Less amount of catalyst,less amount of acetaldehyde oxime and mild reaction conditions were fully extruded the superiority of the method.What's more,this method was suitable for a wide range of substrates,including aromatic nitriles,fatty nitriles and even the nitriles with sensitive groups.In the third chapter,we researched the hydrolyzation and N-alkylation cascade reaction of nitriles and alcohols to synthesize N-alkylamides by using iridium catalyst.In this process,the catalyst[Cp*IrCl2]2 catalyzed two steps reaction from hydrolysis of nitrile to alkylation of primary amides,showed very high catalytic activity.Firstly,we explored the N-alkylation of various nitriles reacted with butyraldoxime and benzyl alcohol;then,we explored cyanophenyl hydrolyzed to corresponding benzamide,then N-alkylation with various alcohols under tandem reaction conditions.The method had the advantages of less catalyst addition,simple operation and broad substrates scope.The product of amides and N-alkylamides obtained by aforementioned methods were characterized by NMR.This study further extended the synthesis of amides and facilitated the use of alcohols as electrophilic reagents in organic synthesis.