Study On The One-Pot Multicomponent Synthesis Of New Spiroheterocyclic Compounds

Following the main line of green chemistry and the principle of"atom economy", and to enhance the efficiency of multicomponent reactions, the traditional synthetic strategy of 1,3-dipolar cycloaddition reaction was changed. In this paper, one-pot multi-component synthetic method for spiroheterocyclic compounds allows 1,3-dipole Azomethine ylide and dipolarophile generated in situ was firstly reported.In the first chapter, multicomponent reactions and their wildly use in the research and development of new pharmaceutical were reviewed firstly, which based on the cycloaddition reactions were introduced especially. Then 1,3-dipolar cycloaddition reaction, azomethine ylide and spiroheterocyclic compounds were summarized.In the second chapter, twenty-seven new dispiropyrrolidines were synthesized by the one-pot four-component reactions of isatin or acenaphthylene-1,2-dione, sarcosine, 1,3-indanedione and aldehyde without any catalyst. Different solvents and the mole ratio of reactants for this MCR were investigated. Using ethanol as solvent and the mole ratio of isatin or acenaphthylene-1,2-dione/sarcosine/1,3-indanedione/aldehyde = 1:1.2:1.2:1 were deemed to the optimum reaction condition. Aromatic aldehydes bearing either electron-withdrawing or electron-donating substituents in the meta or para positions were employed, the reaction proceeded very efficiently in all cases and afforded only one diastereomer of dispiropyrrolidines; while for aromatic aldehydes with ortho substituents, the mixture of two diasteromeric dispiropyrrolidines was obtained. This can be ascribed to the severe steric interaction between the ortho substituents aromatic aldehydes and 1,3-indanedione.In the third chapter, thirteen new spiropyrrolidines were synthesized by the one-pot five-component reactions of indene-1,2,3-trione, benzene-1,2-diamine, sarcosine, aldehyde and 1,3-indanedione or malononitrile. The solventhermal synthesis was firstly employed in 1,3-dipolar cycloaddition reaction while use malononitrile as reactant. The method is fit for green chemistry with the advantages of avoiding the volatilization of solvent and giving a good yield in shorter reaction time.Forty compounds were synthesized, and the structures of all the synthesized compounds were characterized by IR, 1H NMR, 13C NMR, MS and elemental analysis. Three single-crystals were cultured and the structure of the unknown compounds could be confirmed conveniently byΧ-ray single-crystal diffraction analysis.