Nitro quinoline

Among the aromatics, it was found that 4-nitroquinoline N-oxide [56-57-5] is a powerful carcinogen producing malignant tumors when painted on the skin of mice (80). It was further estabUshed that the 2-methyl, 2-ethyl, and 6-chloro derivatives of 4-nitro quinoline oxide are also carcinogens (81). 

The A-oxidation of 3-chloropyridazines increases their reactivity toward methoxide and sulfanilamide anions.The reactivity of 4-chloro- or 4-nitro-quinoline and of chloropyridines toward methoxide ion and piperidine is less than that of the corresponding A-oxides (see Tables II and XI, pp. 270 and 338). The activating effect of the A-oxide moiety in 3-halopyridine A-oxides is greater than that of a nitro group, and in fluoroquinoline A-oxides the activation is transmitted to resonance-activated positions in the adjoining rings. 

The ring expansion of nitronaphthalenes with dimethyl phosphite and sodium methoxide in the presence of strong base to give 2-benzazepines (see Section 3.2.1.4.2.1.) has been adapted successfully to the synthesis of pyridoazepines, e.g. 24, 25, and 26, from 5-, 6-, and 8-nitro-quinoline, respectively43... 

Ar-[2-(dimethylamino)ethyl]-3-r-butyl-2-nitrobenzamide hydrochloride nitro quinolines H /CH3 92... 

Stich, H.F., R.H.C. San, and Y. Kawazoe. DNA repair synthesis in mammalian cells exposed to a series of oncogenic and non-oncogenic derivatives of 4-nitro-quinoline 1-oxide. Nature 229 416-419, 1971. 

Oxidative methylamination of 2-, 3-, 4-, 5-, 6-, 7-, and 8-nitroquinolines at —7 °C leads, as could be expected, to similar results as obtained in the oxidative amination (93LAC823). In general, the methylamination differs from the oxidative amination in several aspects (a) the reaction occurs faster than the amination, due to the higher temperature at which the reaction is carried out, (b) gives higher yields, (c) the site specificity is less than observed in the amination, as it appears by the sometimes occurring formation of mixtures of (methylamino)nitroquinolines, and even in the case of 5-nitro-quinoline formation of bis(methylamino)-5-nitroquinolines (Table III). 

On cooling, the sulfate salt of the 6-methoxy-8-nitro-quinoline partially crystallizes from the reaction mixture. By stirring the mixture, the product comes down as a fine tan, microcrystalline precipitate. This can be isolated and crystallized, but it is more convenient to work it up in the form of the base. 

These methanol washings remove much of the impurities, especially small amounts of unreacted nitroanisidine, with a minimum loss of product. The solubility of 6-methoxy-8-nitro-quinoline in methanol at room temperature is 0.8 g. per 100 g. of solvent and at the boiling point is 4.1 g. per 100 g. of solvent. The solubility in chloroform, on the other hand, is 3.9 g. per 100 g. of solvent at room temperature and 14.2 g. at the boiling point. It is possible to obtain about 12 g. of product by working up these washings, but it is usually not worth the trouble. 

A variant on this reaction makes use of l-anilino-l-methylmercapto-2-nitroethylene as the nitro-synthon. This leads to the 2-anilino-3-nitro-quinolines 88.7S The reaction is best carried out in acetic acid. The condensed thiophene derivatives 89 have been prepared similarly. The use of anthra-... 

The reaction of anilines with nitromalonaldehyde to form the 3-nitro-quinolines (96) is carried out in two steps. The cyclization is best catalyzed by the corresponding aniline hydrochloride in acetic acid (Scheme 19).89,90 The yields range from 40 to 77%, except in the case of o-toluidine, where the yield is very low. The tetracyclic compound 97 has been similarly prepared from 3-aminonaphthostyril.89... 

In addition to the ABC transporters, the MFS family transporters play an important role in clinical drug resistance [161]. The most prominent ones are Mdrl ]162, 163] and Flul ]164]. CaMDRl, formerly known as BEN confers resistance to a variety of different compounds. Cells lacking CaMDRl are susceptible to 4-nitro-quinoline-N-oxide, methotrexate, and cycloheximide ]165, 166]. The closest yeast homologue of CaMDRl is PLRl. As mentioned above, Flrl is known to be involved in drug transport and it mediates resistance to the same spectrum of drugs as CaMDRl. 

The positional selectivity for proton exchange is partly mirrored in nitrations, quinoline gives approximately equal amounts of 5- and 8-nitro-quinolines, whereas isoquinoline produces almost exclusively the... 

The photonucleophilic substitution of five-membered heteroaromatic nitrocompounds has been investigated with the nucleophiles CN-, CNO, OMe-, and water.108 Both 2-nitrofuran and the thiophen undergo smooth substitution of the nitro-group, but 2-nitropyrrole is stable to light. Such substitution reactions may be of synthetic importance as the 2-nitro-compounds are readily available. Light-induced nitro-group replacement has also been observed for 8-nitro-quinoline, which in the presence of a hydrogen donor yields 8-hydroxyquinoline.109 In carbon tetrachloride solution the keto-oxime (52) is reported to be formed. 

Endo, H., Ono, T. and Sugimura, T. (1970) Chemistry and Biological Actions of 4-Nitro-quinoline-1-oxide, Berlin Springer. 

M. Nagao and T. Sugimura, Sensitivity of repair-deficient mutants and similar mutants to 4-nitro-quinoline-1-oxide, 4-nitro-pyridine-l-oxide and their derivatives, Cancer Res. 32, 2369... 

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