The Study Of The New Synthetic Reactions For The Five-membered Heterocyclic Compounds

The alkylation of aromatic N-heterocyclic compounds (pyridine, isoquinoline, quinoline, o-phenanthroline, etc.) with reactive alkylating reagents (phenacyl bromide, benzyl bromide, ethyl bromoacetate, etc.) can afford aromatic quaternary ammonium salts. This kind of quaternary ammonium salts are ionic compounds. Under the action of a strong base, aza-aromatic quaternary ammonium salts can be deprotonated to form aromatic nitrogen ylides. These nitrogen ylides have versatile reactivities and could undergo nucleophilic substitution, nucleophilic addition, Michael addition,1,3-dipolar cycloaddition, and rearrangement reaction. Furtherly the aza-aromatic quaternary ammonium salt and its ylide could be prepared conveniently from simple chemicals. They are often used as important synthons to construct multisubstituted nitrogen-containing heterocyclic compounds in synthetic organic chemistry. On the other hand nitrogen-containing heterocyclic compounds are basic skeletons of many natural drugs such as antiviral drugs, alkaloids and the structural unit of the functional material with very important physiological activity. In this paper we concentrated our research work on the development of new effective synthetic reaction for the five-membered nitrogen-containing heterocyclic compounds. 1. A sequential one-pot two-step reaction for efficient synthesis of pyrrolo[2,1-a]isoquinoline and pyrrolo[1,2-a]quinoline derivatives in good yields has been successfully developed. The reaction included firstly Cu-catalyzed three-component reaction of isoquinoline (quinoline), acetylenedicarboxylate and alkynylbenzene; then Pd-catalyzed or Cs2CO3-promoted intramolecular C(sp)-C(sp2) coupling reaction of initially formed1-alkenyl-2-alkynyl-1,2-dihydroisoquinoline (1,2-dihydroquinoline). 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.2. A series of complex spiro [indoline-3,3’-pyrrolo[1,2-a]quinolines] were efficiently synthesized by1,3-diploar cycloaddition reactions of N-phenacylquinolinium bromides with3-phenacylideneoxindoles in ethanol with triethylamine as base. Under similar conditions the1,3-cycloadditions of N-phenacylisoquinolinium and N-phenacyl-1,10-phenanthrolinium bromides with3-phenacylideneoxindoles resulted in the corresponding spiro [indoline-3,1’-pyrrolo[2,1-a]isoquinoline] and spiro [benzo[h]pyrrolo[1,2-a]quinoline-3,3’-indoline] derivatives in good yields. The characterization data of spiro compounds and single crystal determination indicated that this1,3-cycloaddition reaction is a regioselective and diaseteroseletive reaction and all prepared spiro compounds exist in the thermodynamically stable trans isomer. 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. Under similar conditions the1,3-cycloadditions of N-phenacylisoquinolinium and N-ethoxycarbonylmethylisoquinolinium salts with various isatylidene malononitriles afforded cyano susbtituted [indoline-3,1’-pyrrolo[2,1-a]isoquinoline] derivatives in good yields. All the products were characterized by IR,1H NMR,13C NMR, LC-MS spectroscopy. The single crystal structures of two products were determined by X-ray diffraction method.