Study On The Methodology Of Novel Multicomponent Reaction From Thioacetanilides

In the 20th century, organic synthesis as an important branch of organic chemistry plays a very important role in scientific development and has made great contributions to the development of human society. Now various substances whether it is complex natural products extracted from the nature or the small molecules with biological activity which was designed according to mechanism in vivo or the organic functional molecules which have various physical and chemical properties can be synthesized in the laboratory. Therefore, the research of organic synthesis methods has become particularly important.In the past more than one century, multicomponent reaction has made important contributions to modern organic synthesis and has potential applications in complex organic synthesis. Nowadays, with the development of high capacity screening of biological activity and the coming of gene protein age, the demand of organic compounds for drug research is rapidly increasing. Multicomponent reaction which has unique super synthetic ability has attracted much attention in academic and the business community. The related research to multi-component reaction has become a rapidly developing field since 1995. This paper focuses on one-pot synthesis of tetrahydropyridine derivatives and thiochromeno[2,3-b]pyridines derivatives from functional thioacetanilides.In the first chapter, the overview of the development of the methodology of organic synthesis was briefly introduced. The concept and application of combinatorial chemistry and the broad application of multicomponent reactions in organic synthesis were reviewed in brief. Then the use of thioacetanilides in organic industry and several synthetic methods of pyridine derivatives were introduced.In the second chapter, a series of novel fused tetrahydropyridine derivatives were successfully synthesized by Knoevenagel condensation and tandem annulation from thioacetanilides, aromatic aldehydes and benzoyl acetonitrile. These reactions can occur at very mild condition, convenient and simply purified. To the best of our knowledge, this fused tetrahydropyridine derivatives skeleton has not been reported before.In the third chapter, a series of new thiochromeno[2,3-b]pyridines derivatives were synthesized by tandem [3+3] annulation and intramolecular SNAr ofβ-(2-haloaroyl) thioacetanilides with aromatic aldehydes and benzoyl acetonitrile catalyzed by DABCO. This is a new strategy for the synthesis of thiochromeno[2,3-b]pyridines derivatives, which has not been found in literature. In the fourth chapter, two single-crystals of the two series of target compounds were cultured and the structure of the compounds were ultimately characterized by X-ray single-crystal diffraction analysis.In this paper, thirty-one new compounds were synthesized. The structures of all the target compounds were characterized by the IR, 1 H NMR, 13 C NMR and HRMS. Moreover, the crystal structures of 4i and 5a have been studied by X-ray diffraction.