Study On Selective Reduction Of N-methylanilides Controlled By Reaction Atmospheres

The selective reduction of amide is extremely importance in organic synthesis and in organic chemistry.It has very extensive examples in industrial synthesis,drug synthesis,and natural product synthesis.Usually,the amide compounds are complicated molecules with various functional groups,so whether the selective reduction of amide compounds could be realized,effecting its potential application.Current research of the reduction of amide compounds focused on find and synthesis of reducing agent with different structure to improve the selectivity of the reaction,generate the corresponding target products,including aldehydes,alcohols,imines and amines so on.Among them,the selective reduction of amides to amine compounds is the most important reaction.In this paper,an efficient,catalyst-free and highly selective C-N hydrogenolysis and C-O hydrogenation bond cleavage of N-methylformanilide and its derivatives were studied.Compared with previous methods,this method could achieve highly selective reduction of amide by adjusting the reaction atmosphere without any catalysts.And good substrate scope with many functional group tolerances was demonstrated.It is suitable for the selective reduction of aromatic amides and aliphatic amides,which further expands the synthesis method of amine compounds.The main research content of this article is roughly divided into two parts:(1)The C-N bond cleavage of tertiary formanilides was successfully conducted under nitrogen atmosphere.Under the optimal reaction conditions,the representative aromatic and aliphatic formanilides were screened,affording the corresponding products in high yields(up to 90 %).The reaction has good functional group tolerance and avoids the use of various complex catalysts.(2)The C-O hydrogenation bond cleavage of formanilides has been achieved via altering carbon dioxide atmosphere.The reactions were successfully conducted in 1,4-dioxane at 100 °C with moderate sodium borohydride using N-methylformanilides as model substrates,and the corresponding amines were obtained in over 90% yields.This transformation has higher selectivity without requiring any additives,in line with the concept of green chemistry.