Iron-Catalyzed Aryl Formyl Hydrazone Oxidative Cyclization Into 2,5-Substituted 1,3,4-Oxadiazoles

Aryl formyl hydrazone via oxidative cyclization to preparation of 2,5-substituted 1,3,4-oxadiazoles,that the reaction is a new method.This article choose O₂ as oxidant,since it has simple and easy,environmental protection and clean features,besides its by-product is only H₂ O.When oxygen as the oxidant,there are few instances of the class reactions,that is a valuable research direction.In this paper,the catalyst we also choose the Fe?NO₃?₃·9H₂O that is green,environmental protection,economic and non-toxic,then it is hard to find instance that basic Fe salt as catalyst to synthesis of 2,5-substituted 1,3,4-oxadiazoles.2,5-Substituted 1,3,4-oxadiazoles is a kind of molecular structure which has a wide application in the pharmaceutical,pesticide and material.It has good biological activity in drugs,it also has good photoelectric effect in terms of material.With the above situation shows that Fe salt catalytic and O₂ oxidation synthesis of 2,5-substituted 1,3,4-oxadiazoles has a good significance.First of all,N-amyl benzoyl hydrazone was chosen as a model reaction substrates to probe into the optimal reaction conditions that combined into 2,5-substituted 1,3,4-oxadiazoles with Fe catalytic by oxidative cyclization.Using the O₂ to replace the air in the 100 mL seal tube.Based on the system selection,all kinds of influence factors that include Fe salts,oxidants,additives,solvents,reaction temperatures,reaction time and so on,get the best reaction conditions: The substrate?0.5 eq.?,Fe?NO₃?3·9H₂O?10.0 mol %?,TEMPO?2,2,6,6-tetra-methyl piperidine oxygen??10.0 mol %?,MgSO4?2.0 eq.?,the DCE?CH₂ClCH₂Cl??5.0 mL?.Under the optimum conditions,a series of the substrates can be excellent oxidative cyclization into the target products,which reflects a good functional group tolerance.Second,N-benzyl benzoyl hydrazones as the research of the second part,continue to be studied with Fe salt for the substrate catalytic ring combined into 2,5-substituted 1,3,4-oxadiazoles.Through screening again for experimental conditions,and finding its optimal conditions,that other conditions are all the same but the solvent is replaced by DCM?CH₂Cl₂?.Under the optimal conditions,the scope of substrates focuses on benzyl,which also reflected the good functional group tolerance.In addition,when benzyl into aliphatic groups,the yields of reaction are reduced,so the optimal condition for screening again and get the optimal condition that is the TEMPO of the inputs 15 mol %,solvent change DCE.The study of its mechanism,add 0.5 eq.Butylated hydroxytoluene?4-methyl-2,6-di-tert-butyl phenol?,then the reaction was completely suppressed,it show that the reaction is the free radicals reaction.