Studies On The Synthesis Of Novel Heterocyclic Compounds By Tandem Reaction

Heterocyclic compounds are important organic compounds found widely in natural products. They have been widely used in medicine, pesticide and materials due to their unique structural properties and biological activities. Developmenting the methods of new heterocyclic compounds is the pursuit of organic chemists. Tandem reaction is a concise and efficient protocol for construction of complex organic molecules with biological activities and has been widely used in the construction of natural-like heterocyclic skeletons. In this thesis, some novel bridged heterocyclic and polyheterocyclic compounds have been synthesized by the tandem reaction using some simple and easily available multi-active center synthon as substrates. This study contains six parts of work.In the first part, the progress of the tandem reactions and their applications in the construction of different heterocyclic compounds in recent years are reviewed.In the second part, a series of novel bridged heterocyclic compound 2H-9,15,10-(epibutane[1,1,4]triyl)-2,6-epiminobenzo[4,5]azocino[1,2-a][1,3]diazocine-9,15-dicarbonitrile have been synthesized by the six-component domino reaction of glutaraldehyde, malononitrile, cyclic 1,3-dicarbonyl compounds and amines under microwave irradiation catalyzed by piperidine. In this one-pot transformation, 11 new bonds and five new rings have been formed. The reaction mechanism has been proposed and supported by control experiments and density functional theory calculations of the possible configuration of some intermediates. The structures of products were identified by their IR, 1HNMR,13 C NMR and HRMS analysis. The structures of compounds 5aa and 7b were further confirmed by single crystal X-ray diffraction analysis. This method has the advantages of high regioselectivity, high efficiency, atom-economy and environmental friendliness.In the third part, a series of dibenzo[b,g][1,8]naphthyridin-1(5H)-one and 1H-chromeno[2,3-b]quinolin-1-one derivatives has been synthesized by the tandem reaction of 2-chloroquinoline-3-carbaldehydes and enaminones or dimedone. Most of the [1,8]naphthyridin-1(5H)-one synthesized were evaluated for their antiproliferative in vitro against cancer cells and several compounds were found to have high activities. The structures of products were identified by their IR, 1HNMR,13 C NMR and HRMS analysis. The structures of compounds 16 aa and 17 ha were further confirmed by single crystal X-ray diffraction analysis.In the fourth part, A facile and efficient one-pot procedure for the preparation of functionalized dibenzo[b,g][1,8]naphthyridin-1(2H)-ones via the three-component domino reaction of 2-chloroquinoline-3-carbaldehyde, enaminones and cyclic 1,3-dicarbonyl compounds catalyzed by L-proline is described. This protocol has the advantages of short reaction time, high yield, convenient operation and environmental friendliness.In the fifth part, a series of 4b,9b-(epoxyetheno)indeno[1,2-b]indole-11-carbonitrile derivatives has been synthesized via the three-component reaction of ninhydrin, enaminones and malononitrile catalyzed by L-proline. In this transformation, five new bonds and two rings have been formed. This method has the advantages of environmental friendliness, good yield and simple operation. The structures of products were identified by their IR, 1H NMR, 13 C NMR and HRMS analysis. The structure of compound 24 o was further confirmed by single crystal X-ray diffraction analysis.In the sixth part, A palladium-catalyzed sequential C-H activation/cyclization tandem reaction of N1-benzyl-N2,N3-diisopropyloxalamides with allyl acetates with oxalyl amide as a directing group providing dihydroisoquinoline derivatives has been developed. After removing the directing group, the aromatization product isoquinolines were obtained. This protocol proved an efficient and convenient method for the construction of isoquinoline skeleton.