The Application Of Isocyanides In The 1, 3-Dipolar Cycloaddition Reactions

The multicomponent reaction(MCRs),which enable us to get the multifunctional compounds through rapid,efficient and environmentally friendly method,have attracted considerable interest in the last one centuries.Isocyanide based multicomponent reaction(IMCRs) are particularly interesting by virtue of their versatile.The zwitter ionic intermediates,formed by the addition of an isocyanide to a dimethyl acetylenedicarboxylate(DMAD),occupied most proportion in recent years.Generally, the intermediate can be as a catalyst and a reactant in further reaction,and their nucleophilicity were maintained.The 1,3-dipolar cycloaddition reaction Cycloaddition reactions are one of the most important class of reactions in synthetic chemistry.Within this class,azomethine imines ylides have found extensive use as a method for the synthesis of many bridgehead nitrogen heterocyclic compounds.In this paper,we presented our detailed investigations on the application of isocyanides in the 1,3-dipolar cycloaddition reactions.This one pot,three component reaction gave a new and convenient way for synthesizing pyrazolo[1'2-a]pyridazine derivatives under mild conditions in good yield(60%-85%).All the reactions were carried out in chloroform at reflux for 12 h.The structures of products further confirmed by from X-ray crystallographic analysis,IR,¹H NMR,¹³C NMR spectras and elemental analysis. In addition,on the basis of the electrons and structures of products,we established the mechanism of this reaction in an experimental manner.It is reasonable to assume that the functionalized pyrazolo[1,2-a]pyridazine derivatives may result from Michael addition of the isocyanides to DMAD and subsequent formation of the zwitter ionic intermediate,followed by attack of the 1,3-dipolars which can be produced.