The Study Of Multicomponent Reactions Of Aza-aromatic Quaternary Ammonium Salts

Aromatic quaternary ammonium salts, which can be generated by alkylation of aromatic nitrogen-containing heterocyclic compounds with alkyl halides, could be deprotonated by base to give the active nitrogen ylides. The sequential reaction of the nitrogen ylides with alkenes, alkynes, or nucleophile have been resulted in versatile heterocyclic compounds. Nitrogen-containing heterocyclic compounds such as multi-substituted isoquinoline derivatives or pyrroloisoquinoline derivatives are important substances with biological activity and medical values. The developments of the efficient synthetic method of them have become one of the important important subjects of chemistry.Multicomponent reaction (MCR) is the efficent one-pot synthetic reaction with at least three starting materials. Due to its simple process, easy operation, efficient and high atom economy, this method has been widely studied these days and has become a powerful tool for the rapid synthesis of diverse heterocyclic compounds. So we have carried out a series of MCRs with aromatic nitrogen-containing heterocyclic compounds such as isoquinoline, pyridine.1. The unprecedented isoquinolinium zwitterionic salts with an unusual C-4substitution pattern were efficiently prepared via the multi-component reactions of in situ formed N-benzylisoquinolinium bromide with aromatic aldehydes and cyclic1,3-dicarbonyl compounds. All products were characterized by IR,1H NMR,13C NMR, HRMS spectroscopy. The single crystal structures of two representative compounds were determined by X-ray diffraction method.2. A sequential one-pot two-step tandem reactions for selective and efficient synthesis of pyrrolo[2,1-a]-isoquinoline and its dihydro-and tetrahydro-detivatives has been developed. The tandem reactions of isoquinoline, a-halogenated methylene compounds, aromatic aldehydes, and cyanoacetamide firstly give tetrahydropyrrolo[2,1-a]isoquinolines. Its dihydro-and tetrahydro-detivatives can be obtained directly by controlling oxidation with DDQ. The mechanism of this tandem reaction involved the1,3-dipolar cycloaddition of isoquinolinium ylide as the key step. All the products were characterized by IR,1H NMR,13C NMR, LC-MS spectroscopy. The single crystal structures of five products were determined by X-ray diffraction method.3. An efficient, one-pot tandem reaction of pyridine, a-haloacetate, an aromatic aldehyde and cyclohexane-1,3-dione, dimedone or4-hydrocoumarin in acetonitrile was developed by using1,4-diazabicyclo-[2.2.2]octane as a base catalyst. The2,3,6,7-tetrahydro-4(5H)-benzo-furanones and2,3-dihydrofurocoumarins were obtained in a diastereoselective manner via a mechanism involving in situ formation of a pyridinium ylide. All the products were characterized by IR,1H NMR,13C NMR, LC-MS spectroscopy. The single crystal structures of four products were determined by X-ray diffraction method.