8-Methyl-2-quinolone

N.27) 2(177)-quinolinone, 4-methyl-, 4-methyl-2-quinolone, 4-methyl-1 (H) -qulnolin-2-one [607-66-9] tautomeric form 2-quinolinol, 4-methyl-, 4-methylquinolin-2-ol, 2-hydroxy-4-methylquinoline [84909-43-3]... 

The different long-range coupling of a methyl group to the ortho hydrogen in 4-methyl-2-quinolone (J = 1.3 Hz) and in 4-methyl-2-chloroquinoline (J = 1.0 Hz) may be attributed to a lower aromaticity of the former relative to the latter.279... 

Evodia rutaecarpa (Juss.) Berth Wu Zhu Yu (Evodia) (fruit) Alkyl methyl quinolone alkaloids, evodiamine, limonin, evocarpine, rutaecarpine, N-methyl anthranilic acid, evodol, hydroxyevodiamine, N-methylanthranflamide, N,N-dimethyl-5 -methoxytryptamine, dehydroevodiamine.32,33,237 Antiemetic, analgesic, lower blood pressure, antibacterial. 

The reaction of haplophyllidine (11) or its hydration product, perforine (12), with concentrated sulphuric acid results in dehydration, loss of methanol, and cyclization the structure (13) of the product was established by spectroscopy and by conversion, with methyl iodide, into the corresponding N-methyl-4-quinolone. The reaction of the Haplophyllum alkaloid haplatine (14) with methyl iodide also results in formation of an N-methyl-quinolone ( 15), and in this case the methylation of the allylic hydroxy-group gives a second product (16). Reductive cleavage of haplatine furnishes the 3-ethyl-2-quinolones (17) and (18). ... 

Transition-metal-catalyzed C-aUcylation methods have been successfully applied to the alkylation of several methyl-A-heteroaromatic compounds, including methyl pyrimidines and methyl quinolones. 

With regard to the alkylation of methyl quinolones, Obora and co-workers reported that the reaction of 2-methylquinoline (3.0 mmol) with benzyl alcohol (1.0 mmol) in the presence of [Ir(OH)(cod)]2 (5 mol%) combined with PPh3 (20 mol%) and t-BuOK (50 mol%) in 1,4-dioxane at 130 °C gave the desired C-alkylated product in 92 % isolated yield (Scheme 30) [175]. 

Zang Z, Zhou W, Yu A (2004) Synthesis and antibacterial activity of 7-(substituted)amino-methyl quinolones. Bioorg Med Chem Lett 14 393-395... 

Recently kinetic data have become available for the nitration in sulphuric acid of some of these hydroxy compounds (table 10.3). For 4-hydroxyquinoline and 4-methoxyquinoline the results verify the early conclusions regarding the nature of the substrate being nitrated in sulphuric acid. Plots of log Q against — (Lf + logioflHao) fo " these compounds and for i-methyl-4-quinolone have slopes of i-o, i-o and 0-97 at 25 C respectively, in accord with nitration via the majority species ( 8.2) which is in each case the corresponding cation of the type (iv). At a given acidity the similarity of the observed second-order rate constants for the nitrations of the quinolones and 4-methoxy-quinoline at 25 °C supports the view that similarly constructed cations are involved. Application of the encounter criterion eliminates the possibilities of a... 

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-hydroxyquinoline) 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 r-methyl-4-quinolone the total yield of nitro-compounds was not high (table ro.3). 

Echinopsine. From Echinops Ritro (seeds) and other Echinops spp. Greshoff isolated this alkaloid, which Spath and Kolbe have shown is l-methyl-4-quinolone. Greshoff also obtained from the same source fi-echinopsine, m.p. 135°, and echinopseine. 

Deactivation in the anion formed under the reaction conditions prevents alkoxy-dechlorination of 4-chloro-2-quinolone (222) with boding alkoxide solution while 4-chloroquinoline and its 2-ethoxy and 2-anilino derivatives react. 4-Chloro-iV -methyl-2-quinolone reacts readily. 

In cyclization of 6-aminoethylene substituted 1-methylbenzimidazole, an angularly annelated l//-l-methyl-8-ethoxycarbonyl-9-oxo-6,9-dihydroimidazo[5,4-/] quinolone 122 prevails over the sterically less hindered (9-oxo group vs 1-methyl group) linearly annelated imidazo[4,5-g]quinoline 123. Hydrolysis of the cyclization product produced the corresponding acid 124 (Scheme 39) (94CCC1145). 

These amines gave, with methyl propiolate, products of Michael mono- and bis-addition. Adducts underwent further reaction leading to triazolo[4,5-/]quinolones 181, after retro Diels-Alder reaction and acetylene elimination to its methoxycar-... 

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

X-ray investigations on 3,3-bis(tcrt-butoxycarbonyl)-4,5-difluoro-l-methyl-7-oxo-2,3-dihydro-l//,7//-pyrido[3,2,l-(/]cinnoline-8-carboxylate 57 revealed, that 1-methyl group is perpendicular to the plane of the 4-quinolone moiety (96BCJ1371). 

As a part of the total synthesis of (+ )-corydalic acid methyl ester (12), a reaction of a cyclic enolate with an imine has been applied. The 2-toluamide enolate 9, which in this case is substituted at the methyl group, adds stereospecifically to imine 10, affording mainly tram-iso-quinolone 11 with a d.r. (transjds) > 95 525. 

A kinetic study of the deuteration of pyridones and quinolones by deuterated sulphuric acid yielded the data in Table 148sl0. For the 4-pyridones, the rapid rise in rate with increasing acidity in strongly basic solutions, and the levelling off in rate at about H0 = 0 is consistent with reaction on the free base as is the small negative entropy of activation. The similarity in rate between 4-pyridone and its 1-methyl derivative shows reaction to take place on the form (XII) and not (XIII), viz. 

The Jacobs-Gould intramolecular cyclization of diethyl N-(6-methyl-2-pyridyl)amino-methylenemalonate to 3-ethoxycarbonyl-7-methyl-l,8-naphthyrid-4-one is another reaction ideally suited to microwave heating, although conductively heated equipment was employed for laboratory-scale experiments [45]. The product is a key intermediate in the synthesis of nalidixic acid, the first of the quinolone antibacterials. The process usually is conducted at temperatures of 200-250 °C and in high dilution, with heat transfer oils such as the eutectic mixture of diphenyl ether and biphenyl. However, it proceeded rapidly, predictably and controllably under solvent-free conditions. 

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