Design, Synthesis And Characterization Of Fused Heterocyclic Compound Containing Quinoline Skeleton

Quinoline and its derivatives, as a class of significant nitrogen heterocyclic compounds, have been playing an important role in medicinal and organic chemistry. It was discovered that numerous heterocyclic-fused quinolines had exhibited potent anti-tumor and anti-cancer activities. As a consequence, extensive synthetic efforts have been invested in the design and synthesis of polycyclic-fused quinoline derivatives for current medicinal chemistry needs.. In this thesis, starting from ethyl 4-(bromomethyl)-2-(chloromethyl)-2-(chloromethyl)quinoline-3-carboxylate and 5-methyl-1H-pyrano[3,4-b]quinolin-4(3H)-one as the substrates, we successfully synthesized a variety of novel and interesting polycyclic-fused quinoline compounds.In the first part, we surveyed the related literatures in the last few years, wherein we made a comprehensively discussion concerning the chemical properties and synthetic methods to quinoline derivatives, 2-benzofuran compounds, acridine and acridone compounds, respectively.In the second part, we employed ethyl 4-(bromomethyl)-2-(chloromethyl) quinolin-3-carboxylate(2) as the substrate to carry out the one-pot reaction with salicylaldehyde and substituted salicylaldehyde in acetonitrile medium with the use of K2CO3 as weakly basic catalyst and PEG-400 as a phase transfer catalyst. After the reaction was complete followed by simple workup, the compounds 2,4-di(benzofuran-2-yl)quinoline-3-carboxylic acid derivatives(3a~h) were identified as the reaction products. Further, we used o-hydroxyacetophenone and its derivatives to subject to the reaction under the same reaction time. To our delight, the expected products 2,4-bis(3-methylbenzofuran-2-yl) quinoline-3-carboxylic acid derivatives(4a~c) could also be obtained with good yields. The structures of all the synthesized compounds were confirmed by IR, 1H NMR, 13 C NMR, ESI-MS and HR-MS spectra.In the third part, ethyl 4-(bromomethyl)-2-(chloromethyl)quinolin-3-carboxylate(2) as the substrate was treated with triethylphosphite to afford phosphorus ylide intermediates, which further reacted without isolation with respective benzaldehyde or substituted benzaldehydes, naphthaldehyde and heterocyclic aldehyde to give the corresponding ethyl 2,4-di((E)-styryl)quinoline-3-carboxylates(5a~w). The structures of all compounds were confirmed by IR, 1H NMR, 13 C NMR, ESI-MS and HR-MS spectral data.In the fourth part, we firstly used ethyl 2-(chloromethyl)-4-methylquinoline-3-carboxylate(1) as substrate to carry our the Williamson reaction in order to construct the diester intermediate(6), which was underwent the Claisen condensation reaction to obtain ethyl 5-methyl-4-oxo-3,4-dihydro-1Hpyrano[3,4-b]quinoline-3-carboxylate(7) using 18% diluted hydrochloric acid to give 5-methyl-1H-pyrano [3,4-b]quinolin-4(3H)-one(8). Thus, the resuling compound(8) reacted with o-amino carbonyl compounds and isatin as well as substituted isatins to obtain the corresponding 14-methyl-6H-pyrano[3,2-b:5,4-b’] diquinoline derivatives(9a~d) for 4 exampes and 14-methyl-6H-pyrano [3,2-b:5,4-b’]diquinoline-8-carboxylic acid derivatives(10a~r) for 18 examples. The structures of all the compounds were confirmed by IR, 1H NMR, 13 C NMR, ESI-MS and HR-MS spectra.In the fifth part, we selected 5-methyl-1H-pyrano[3,4-b] quinolin-4(3H)-one(8) as the raw material to conduct the Aldol condensation reaction under solvent-free grinding conditions with aromatic aldehydes to synthesize(Z)-3-benzylidene-5-methyl-1H-pyrano[3,4-b]quinolin-4(3H)-one derivatives(11a~r). The structures of all compounds were confirmed by IR, 1H NMR, 13 C NMR, ESI-MS and HR-MS spectra.