4-Quinolone nitration

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). 

The same methodology was also used starting from the ethyl 6-amino-7-chloro-l-ethyl-4-oxo-l,4-dihydroquinoline-3-carboxylate, prepared by reduction of the nitro derivative. The requisite nitro derivative was prepared by nitration of ethyl 7-chloro-l-ethyl-4-oxo-l,4-dihydroquinoline-3-carboxylate. A second isomer was prepared from 4-chloro-3-nitroaniline by reaction with diethyl ethoxymethylene-malonate, subsequent thermal cyclization, and further ethylation because of low solubility of the formed quinolone. After separation and reduction, the ethyl 7-amino-6-chloro-l-ethyl-4-oxo-l,4-dihydroquinoline-3-carboxylate 32 was obtained. The ort/io-chloroaminoquinolones 32,33 were cyclized to the corresponding 2-substituted thiazoloquinolines 34 and 35, and the latter were derivatized (Scheme 19) (74JAP(K)4, 79CPB1). 

N-ethyl nitro qninolones 6 E328 N-ethyl-6-nitro-2-quinolonium nitrate 6 E328 N-ethyl-5 (-6 or -7)-trinitro-2-quinolone 6 E329... 

Inorganic silver salts are strongly bactericidal. Silver nitrate, 1 1000, has been most commonly used, particularly as a preventive for gonococcal ophthalmitis in newborns. Antibiotic ointments have replaced silver nitrate for this indication. Silver sulfadiazine slowly releases silver and is used to suppress bacterial growth in burn wounds (see Chapter 46 Sulfonamides, Trimethoprim, Quinolones). 

As outlined above, the orientation of substitution in bicyclic benzazines frequently occurs preferentially at the 5- and/ or 8-positions. However, when the heterocyclic ring contains a carbonyl group, the orientation of substitution in a fused benzene ring frequently occurs in the 6-position, for example for 2-quinolone 618 (Z = NH) (nitration, H2SO4HNO3, 20 C) and for coumarin 618 (Z = 0) [nitration (H2S04HN03) and sulfonation (H2S04)], and this can be compared with the /wra-substitution of acetanilide and phenyl acetate, respectively. 

N12.84% yel ndls (ale), mp 183°, subl. Prepd by nitrating the parent, heating ethyliodide with.sodium -6mitro-2-quinolonate, or by the potassium ferricyanide oxidation as with the... 

The position of electrophilic substitution of quinolones and isoquinolones depends upon the pH of the reaction medium. Each type protonates on carbonyl oxygen, so reactions in strongly acidic media involve attack on this cation and therefore in the benzene ring the contrast is illustrated below by the nitration of... 

Syntheses of the antibiotic compounds deoxynybomycin (100) and nybomycin (102) as well as related heterocyclic compounds have been described (Scheme 7). The 8-hydroxy-2-quinolone (97), readily prepared from o-anisidine in three steps, was converted into the fused oxazoline-quinoline derivative (98) by successive nitration, reaction with dibromomethane, and hydrogenation. Adaptation of the Doebner-von Miller quinoline synthesis to (98) provided the tetracyclic product (99), which upon methylation and oxidation gave deoxynybomycin (100) in 0.83% overall yield from o-anisidine. The key intermediate... 

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