2-Quinolone, from quinoline

The formation of 2-quinolone from quinoline, which is brought about by the action of alkali hydroxides at high temperature, can be formally regarded as an S Ar process with a hydride ion as leaving group ... 

Baylis-Hillman adducts such as 55 and 56 derived from 2-nitrobenzaldehydes were shown to function as useful precursors to functionalized (1H)-quinol-2-ones and quinolines. Treatment of 55 and 56 with iron and acetic acid at 110 °C afforded 57 and 58, respectively <02T3693>. A variety of other cyclization reactions utilized in the preparation of the quinoline scaffold were also reported. An iridium-catalyzed oxidative cyclization of 3-(2-aminophenyl)propanols afforded 1,2,3,4-tetrahydroquinolines <02OL2691>. The intramolecular cyclization of aryl radicals to prepare pyrrolo[3,2-c]quinolines was studied <02T1453>. Additionally, photocyclization reactions of /rans-o-aminocinnamoyl derivatives were reported to provide 2-quinolones and quinolines <02JHC61>. Enolizable quinone and mono- and diimide intermediates were shown to provide quinolines via a thermal 6jt-electrocyclization <02OL4265>. Quinoline derivatives were also prepared from nitrogen-tethered 2-methoxyphenols. The corresponding 2-methoxyphenols were subjected to a iodine(III)-mediated acetoxylation which was followed by an intramolecular Michael addition to afford the quinoline OAc O... 

Simple quinoline alkaloids have been isolated from several genera - e.g., 4-methoxy-l-2-quinolone from Fagara boniensis, and edulitine from Casimiroa edulis. 

Ca.ta.lysts, A small amount of quinoline promotes the formation of rigid foams (qv) from diols and unsaturated dicarboxyhc acids (100). Acrolein and methacrolein 1,4-addition polymerisation is catalysed by lithium complexes of quinoline (101). Organic bases, including quinoline, promote the dehydrogenation of unbranched alkanes to unbranched alkenes using platinum on sodium mordenite (102). The peracetic acid epoxidation of a wide range of alkenes is catalysed by 8-hydroxyquinoline (103). Hydroformylation catalysts have been improved using 2-quinolone [59-31-4] (104) (see Catalysis). 

Angularly annelated H- -methy 1-8-ethoxy carbonyl-9-oxo-6,9-dihydrotriazolo [5,4-/]quinolone is formed preferably 164 over the sterically less hindered (9-0X0 group vs 1-methyl group) linearly annelated triazolo[4,5-g]quinoline 165 in a reaction starting from 6-aminoethylene substituted 1-methyIbenzotriazole. Hydrolysis of the cyclization product produced the corresponding acid 166 (Scheme 52) (94CCC1145). 

In this chapter, an attempt has been made to present a total number of 20 QSAR models (12 QSAR models for topo I inhibitors and eight QSAR models for topo II inhibitors) on 11 different heterocyclic compound series (an-thrapyrazoles, benzimidazoles, benzonaphthofurandiones, camptothecins, desoxypodophyllotoxins, isoaurostatins, naphthyridinones, phenanthridines, quinolines, quinolones, and terpenes) as well as on some miscellaneous heterocyclic compounds for their inhibition against topo I and II. They have been found to be well-correlated with a number of physicochemical and structural parameters. The conclusion, from the analysis of these 20 QSAR, has been drawn that the inhibition of topo I is largely dependent on the hydrophobicity of the compounds/substituents. On the other hand, steric parameters (molar refractivity, molar volume, and Verloop s sterimol parameters) are important for topo II inhibition. 

American Home Products has patented molecules ranging from substituted quinoline, piperidine, and naphthpyridine compounds as immunomodulators. Ciprofloxacin, a quinolone antibiotic, reduced the extracellular IL-1 activity in human monocytes and delayed the peak production of IL-la IL-(3 by 24 h and decreased total IL-113 production, but did not change total IL-la production [75,76]. 

Intermolecular cycloaddition reactions include that of (158) and RCH = CHOEt to give quinoline (159). The 2-quinolone (161) is obtained from (160) and HC = COEt. 

Non-hemiterpenoid Quinolines.—A re-examination of the alkaloids of Haplophyllum dubium resulted in the isolation of two members of the 2-aryl-4-quinolone group, i.e. graveoline (2 R = Me) and the new alkaloid norgraveoline (2 R = H).5 A new bacterial pseudan (3) has been obtained from Pseudomonas aeruginosa.8... 

The first dimeric quinoline alkaloid, pteledimerine, was isolated recently from the root bark of Ptelea trifoliata (cf. Vol. 10, p. 80). Several related compounds have now been found in the same species, and the structure of one of them, pteledimeridine (16), was elucidated mainly by means of H n.m.r. and mass spectroscopy.9 The two dimeric alkaloids are isomeric and differ only in the nature of the furoquinolone portion, which has angular annelation (2-quinolone) in pteledimeridine and linear annelation (4-quinolone) in pteledimerine. 

The case of i-methyl-4-quinolone is puzzling. The large proportion of the 3-nitro isomer formed in the nitration (table 10.3 cf. 4-hydroxy-quinoline) might be a result of nitration via the free base but this is not substantiated by the acidity dependence of the rate of nitration or by the Arrhenius parameters. From i-methyl-4-quinolone the total yield of nitro-compounds was not high (table 10.3). 

Small structural changes from these quinolines to quinolones shift the activity to... 

The reduction of 2, either catalytically or with zinc in acetic acid, leads to 3-amino-4-hydroxy-2-quinolone 20 [72TH000], These amino compounds are rather unstable they dimerize with loss of ammonia to "bis-amines", which in turn are readily oxidized to dyes similar to those obtained from ninhydrin and primary amines [68M1205] [68M1543], The amino derivatives 20 are therefore conveniently converted into 0,N-diacetyl derivatives, the N-acetyl derivative 21, or its dehydrated form, the oxazolo derivative 22 [95MI000], The variety of biological activity of oxazolo-quinolines of type 22 has been detected only in recent years [94JHC1647],... 

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