Construction Of Heterocyclic Skeleton Using Multicomponent Reactions

Multicomponent reactions(MCRs) are an ecofriendly protocol because of the obviation of the need for isolation and purification of the intermediates results in maximization of yields and reduction of waste. The creation of diverse and complex molecules from readily available starting materials is a challenging theme. Multicomponent reactions(MCRs) have become especially important in this regard because of their convergent character, atom economy and operational simplicity. In this thesis, some novel heterocyclic skeletons have been constructed by multicomponent reactions(MCRs) using simple cheap and easily-available sython. The whole work composed of following six parts:In the first part, it is the summary of recent progress on the study of the multicomponent reactions(MCRs) and the bases of the selection of the subject.In the second part, a facile and efficient method for the synthesis of polysubstituted pyrroles have been developed via a novel four-component domino reaction of arylglyoxals, anilines, dialkyl but-2-ynedioate or alkyl acetoacetate and malononitrile under catalyst-free conditions. In accordance with reports from the literature and density functional theory calculations, we propose the mechanism for the reaction. The structures of the products were identified by IR, 1H NMR, 13 C NMR and HRMS. The structure of compound 5ar was further confirmed by X-ray diffraction analysis.In the third part, an environmentally benign and efficient method has been developed for the synthesis of functionalized tetrahydroindole derivatives in aqueous media under catalyst-free conditions, by simply combining a phenylglyoxal monohydrate, an enaminone, and a barbituric acid. The advantages of this method are that it is catalyst-free, has an easy work-up, provides good yields, and uses water as solvent, which make this procedure facile and practical. The structures of the products were identified by IR, 1H NMR, 13 C NMR and HRMS. The structure of compound 10 b was further confirmed by X-ray diffraction analysis.In the fourth part, a concise and efficient domino reaction has been developed for the synthesis of polyfunctionalized indenopyridine and hydroisoquinoline derivatives via the cleavage of a C-C bond. This reaction provides facile access to complex nitrogen-containing heterocycles by simply mixing three common starting materials in EtOH catalyzed by NaOH under microwave irradiation conditions. The structures of the products were identified by IR, 1H NMR, 13 C NMR and HRMS. The structures of compounds 13 h, 15 a and 17 a were further confirmed by X-ray diffraction analysis.In the fifth part, two series of novel functionalized polyhydroisoquinoline derivatives have been synthesized via the three-component domino reaction of glutaraldehyde and malononitrile with β-ketoamides catalyzed by Et3 N. This reaction represents the first reported process for the facile conversion of a β-ketoamide to a hydroisoquinoline via a C-N bond cleavage reaction. The structures of the products were identified by IR, 1H NMR, 13 C NMR and HRMS. The structures of compounds 18 c and 19 c were further confirmed by X-ray diffraction analysis.In the sixth part, a synthesis of dihydroisoindole derivations is described via three-component reactions of phthalaldehyde, aniline and malononitrile under catalyst-free conditions in HFIP is described. The structures of the products were identified by IR, 1H NMR, 13 C NMR and HRMS. The structure of compound 20 g was further confirmed by X-ray diffraction analysis.