Study On The Synthesis Of Imidazo[1,2-α]Pyridine Derivatives Using The Heterocyclic Ketene Aminals And Thioamides As Synthons

Heterocyclic ketene aminals are a class of very important synthons in the form of heterocyclic compounds because of its high reactivity. Thioamides as a class of particular polarized ketene N, S-acetals with general structures, are also important synthons and applied to construct heterocyclic systems. New strategy of organic synthesis-multicomponent tandem reaction can synthesize libraries of compounds with structural diversity rapidly, by virtue of their atom economy, ease of execution, and generally high yields of products. The thesis focuses on constructing new framework of imidazo[1,2-a]pyridines from high functional heterocyclic ketene aminals and thioamides using "one-pot" method. This method is flexible, which contains the advantages of catalyst-free, high yield and mild conditions in various and oriented synthesis.In this thesis, tetrahydroimidazo[1,2-a]pyridine derivatives unreported in the literatures have been synthesized by the multicomponent tandem reactions via heterocyclic ketene aminals and thioamides in the absence of any catalyst. The reaction conditions including solvent, catalyst and temperature were examined. The optimal condition was molar ratio of heterocyclic ketene aminals, aromatic aldehydes, thioamides with1:1:1and methanol as solvent without any catalyst. The intermediates did not need to be separated, and then proceeded intramolecular regio-selecti" cyclization reactions in the presence of DMF/K2CO3or CH3OH/H2SO4to obtain t final products in high yields. These reactions were very mild, convenient and effective.31target compounds were synthesized.In this reaction, one new ring and four new bonds were constructed via a sequence of Knoevenagel condensation, aza-ene reaction, regio-selective cyclization reactions.The structures of all the target compounds were confirmed by IR,1H NMR,13C NMR, and HRMS, and the unambiguous molecular structure was determined by X-ray diffraction analysis. The plausible mechanism was also presented.