Study On Construction Of Heterocyclic Compounds With Multicomponent Reactions

Multicomponent reaction (MCR) is the one-pot method for the synthesis of compoundsby taking many substrates into a reactor without separating intermediate products. Becauseof its simple operation, continuous reaction, atom economy, and meeting the need oforganic and pharmaceutical synthesis, this method has brought the much attention of people.In this dissertation, we designed and prepared some containing nitrogen, oxygen and sulfurheterocyclic compounds using multicomponent reactions. At first, the recent review ofsynthesis heterocyclic compounds using multicomponent reaction at home and abroad wasintroduced. The contents, purpose, significance and the operation of multicomponentreaction experiments about this dissertation were also involved in this part.The larger steric hindrance pyrimidines have been synthetized by one-potmulticomponent reaction of1,2-diphenylethanone, aromatic aldehydes and urea (orguanidine carbonate) under solvent-free conditions. At the same time, somenitrogen-containing polydentate ligands have been prepared from the raction of aromaticaldehydes,1-(pyridin-2-yl)ethanone and guanidine carbonate (or cyanoguanidine). In partfour, an efficient and convenient method for the preparation of5-amino-dihydrothiophenederivatives by four-component reaction of thiazolidine-2,4-dione, aromatic aldehyde,malononitrile and n-butylamine (or cyclopropanamine, pyridin-3-ylmethanamine) withoutusing any other catalysts was reported. It was found that the thiazolidine-2,4-dione byopening its ring to take part in constructing thiophene derivatives. This is a new process forsynthesis of thiophene derivatives with good adaptability about the different structures ofthe amines, and is different from classical the Gewald reaction. Furthermore, a series of newtype kuinoline derivatives (containing1,4-dihydropyridines core) were synthetized byfour-component reaction of4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3-dione, aromaticaldehyde,5,5-dimethylcyclohexane-1,3-dione (dimedonecas) and ammonium acetatewithout using any catalysts under room temperature. Simultaneously, containing-thienylpyrimidine derivatives were synthetized from4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3-dione, aromatic aldehyde and urea, and this is the new development of Biginellireaction. The advantages of these processes are good selectivity, broad substrate scope, easyconstruction of compounds libraries. In part six, the containing oxygen heterocycliccompounds, xanthydrol derivatives were efficiently prepared by the three-componentreaction of aromatic aldehyde,3,4-dihydronaphthalen-1(2H)-one, and cyclohexanone undersolvent-free conditions. It shows the effectiveness of multicomponent reaction for the synthesis of these complex structures with a very simple operation. The products ofxanthydrol were the first reported. We find an unexpected way to synthesize cyclohexanolderivatives from five-component reaction, and this is the new development for synthesis ofthese compounds. At last, the pyridine compounds have been synthetized viamulticomponent reaction by malononitrile taking part in the reaction, and the unexpectedtetrahydronaphthalene derivatives have been obtained in our research. At the same time, wereported the efficient method for synthesis of isoquinoline derivatives. There are all newprocesses for synthesis of these compounds.The results of the experiment show that multicomponent reaction is an efficient methodfor constructing of nitrogen-containing, oxygen-containin and sulfur-containingheterocyclic compounds. Especially, it may be the best method for constructing somecomplex heterocyclic compounds. Becaue of synthetizing many compounds for each series,there would very easy to constructing small molecule heterocyclic compounds libraries. Inthis dissertation,139compounds have been synthesized and most of them were reported forthe first time. All the structures of the products were confirmed on the basis of IR,1H NMRspectra, and highresolution mass spectrometry (HRMS), and some compounds wereadditionally confirmed by X-ray diffraction analysis. The possible reaction mechanismswere proposed in the text. The advantages of these reported reactions are simple operation,mild reaction conditions, short reaction time, high yields, and atomic economy.