Preparation Of ?-nitro-?-amide Compounds Through The Ritter Reaction

?-nitro-?-amide compounds are very important organic intermediate compounds,which are widely used in biology,medicine and pesticide fields.However,the traditional synthesis methods are too complicated and lack of atom economy.Ritter reaction is a classic synthesis reaction which can be prepared the corresponding amide by reaction of alcohols or olefins and nitriles in the presence of acidic medium.It is not only simple reaction,but also has good atom economy.Therefore,preparation of a-nitro-p-amide compounds through the Ritter reaction has very important application and theoretical significance.In the paper,?-nitro-?-amide compounds were synthesized through the Ritter reaction with the ?-nitro alcohol and nitrile as the raw material.The optimal reaction conditions are followings.The trifluoromethanesulfonic acid(2 eq)is the catalyst.Dichloromethane is the solvent.The reaction temperature was 40? and the reaction time is 24 hours.Under the optimal conditions,a series of a-nitro-?-amide compounds were synthesized and the yield is up to 95%.At the same time,triethylene diamine was found firstly to be an efficient catalyt for the Henry reaction.The optimal conditions of Herry reaction are followings.The triethylene diamine is catalyst(0.5 eq).The nitrile is reacton solvent.the reaction temperature is 0 ?and the reaction time is 24 hours.Henry/Ritter tandem reaction was firstly used as an efficiency method to generate a-nitro-?-amide compounds.The best reaction conditions are followings.On the basis of Henry reaction,the dosage of acetonitrile is 0.5mL and the solvent is methylene chloride(1.5 mL).Trifluoromethanesulfonic acid(3 eq)is catalyst.The reaction temperature is 40 ? and the reaction time is 24 hours.Under the optimal conditions,a series of a-nitro-?-amide compounds were synthesized through Henry/Ritter reaction and the yield is up to 83%.Finally,on the basis of research on Henry/Ritter tandem reaction,we reported that the preparation of amides by the reduction/Adol/Ritter tandem reaction and optimized the conditions.And then 16 different new amides were synthesized and the yield is up to 67%.