Design, Synthesis And Characterization Of Novel Heterocyclic-fused Compounds Containing Benzo[h] Acridone Skeleton

Acridine derivatives are one of the more studied chemotherapeutic compounds,widely used as antimalaria, a antibacterial and antitumor agents. As a consequence, agreat deal of work has been devoted toward new type or structure modifications ofacridine derivatives in order to enhance the potency of acridines in last few years. Inthis thesis, we firstly designed and synthesized the paprent tricyclic compound9,11-dihydro-8H-benzo[h]pyrano[3,4-b]quinolin-8-one by five-step reaction. After thereduction of o-nitobenzaldehyde, the resultig o-aminobenzaldehyde was reacted withacetacetic ester via Friedlander condensation reaction under the catalysis of sodiumethoxide to give benzo[h]ethyl-2-methyl-3-quinoline carboxylate (II), the radicalbromination of which with NBS afforded the corresponding ethyl2-bromomethyl-3-quinoline carboxylate (III). In a Williamson-type reaction, compoundIII reacted with ethyl hydroxyacetate in anhydrous benzene to afford benzo[h]ethyl-2-[(2-ethoxy-2-oxoetho-xy)methyl]quinoline-3-carboxylate(2), which was thenunderwent the intramolecular Claisen condensation reaction under the catalysis ofsodium ethoxide in anhydrous toluene to give the comopund benzo[h]ethyl4-oxo-3,4-dihydro-1H-pyrano-[3,4-b]quinoline-3-carboxylate(3).Keto-enol tautomerismof the compound(3) was investigated by spectroscopic methods. Then, decarboxylationof compound(3) under acidic condition gave the paprent tricyclic compound (4).In the first part, the property and synthesis of9,11-dihydro-8H-benzo[h] pyrano[3,4-b] quinolin-8-one and its derivatives are reviewed on the basis of inspection of the110papers. with hydroxy ethyl acetate via Williamson reaction, Claisen condensationand decarboxylation reaction.In the second part, In a Williamson-type reaction, compound III reacted with ethylhydroxyacetate in anhydrous benzene to afford benzo[h]ethyl -2-[(2-ethoxy-2-oxoetho-xy)methyl]quinoline-3-carboxylate(2), which was thenunderwent the intramolecular Claisen condensation reaction under the catalysis ofsodium ethoxide in anhydrous toluene to give the comopund benzo[h]ethyl4-oxo-3,4-dihydro-1H-pyrano-[3,4-b]quinoline-3-carboxylate(3).Keto-enol tautomerismof the compound(3) was investigated by spectroscopic methods. Then, decarboxylationof compound(3) under acidic condition gave the paprent tricyclic compound (4).theproperty and synthesis of9,11-dihydro-8H-benzo[h] pyrano [3,4-b] quinolin-8-one withhydroxy ethyl acetate via Williamson reaction, Claisen condensation anddecarboxylation reaction.In the third part,(Z)-9-benzylidene-9,11-dihydro-8H-benzo[h] pyrano[3,4-b]quinolin-8-one was prepared by9,11-dihydro-8H-benzo[h] pyrano[3,4-b] quinolin-8-one with hydroxy ethyl acetate via Williamson reaction, Claisen condensation anddecarboxylation reaction. Then, compound18as a versatile intermediate reacted withvarious aldehydes under solvent-free conditions to give a variety of correspondings(5a-q) in the yields of65.5-85.0%. Furthermore,9-phenyl-8H-pyrano[3,2-b:5,4-b’]diquinoline (5r) was prepared by compound4with2-aminobenzaldehyde (5r) underthe condition of EtONa/EtOH via Friedl nder condensation reaction.In the fourth part, Subsequently, compound4as a versatile intermediate reactedwith various aldehydes under solvent-free conditions to give a variety ofbenzo[h]-2-arylidene-bearing3-oxa-acridinones (5a-i). The parent compound4also hasthe Pfitzinger to give the corresponding compounds (5a-i) respectively.In the fifth part, benzo[h]ethyl-2-(chloromethyl)-4-phenylquinoline-3-carboxylate(1)reacted with aniline derivatives to give the corresponding9-phenyl-9,10-dihydro-8H-benzo[h]pyrrolo[3,4-b]quinolin-8-one derivates (7a-m) in the yields of73.6-84.4%...