4-Methyl-8-nitroquinoline

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). 

Electronegative groups do not invariably prevent nuclear bromination, but reaction conditions must be much more severe, and the orientation of substitution may be affected by the substituent. Thus 6-nitroquinoline was brominated in sulfuric acid at 100°C to give the 8-bromo product (71) in 51% yield 8-methyl-5-nitroquinoline gave a 69% yield of the 7-bromo derivative (72) under similar conditions, whereas 7-chloroquinoline was transformed into the 5-bromo product (93%) (88CHE892) (Scheme 35). In a sealed tube reaction with bromine, 8-nitroquinoline gave a mixture... 

Nitropyridine yields a mixture of 2-, 4- and 6-amino-3-nitropyridines by this method142. An amino group is introduced into the 2-position of l,n-dinitronaphthalenes (.n = 3-8)143 and various 5- and 8-nitroquinolines, such as 8-methyl-5-nitroquinoline and 6-chloro-8-nitroquinoline, have been aminated adjacent to the nitro group144. Pteridines are converted into alkylarnino derivatives by the action of a solution of potassium permanganate in an alkylamine, e.g. equation 51145. 

Methylquinoline in sulfuric acid below 5 °C nitrates at positions 6 and 8 7-methylquinoline gives 7-methyl-8-nitroquinoline (77T1765). 

A new approach to the synthesis of 4-alkoxy-l-methyl-2-quinolones has been described (Scheme 3).18 Irradiation of 4-alkoxy-2-methylquinoline 1-oxides (12) (prepared from 2-methyl-4-nitroquinoline 1-oxide) results in photo-rearrangement to give the 2-quinolones (13) as major products a mechanism (Scheme 3) has been proposed. The alkaloids (13 R = Me) and ravenine (13 R = CH2CH=CMe2), which have been synthesized by other means, were prepared in this way. 

Cycloheximide (CYH), 4-nitroquinoline-oxide (4-NQO), sulfomethuron methyl (SMM), and 5-fluoro-orotic acid (5FOA) (BioMol, PA). 

Isatin has been reported to yield 3-nitrocinchoninic acid (92 R = C02H) with nitromethane in aqueous KOH.83 Although this seems like the use of a type 1 synthon, it is more appropriate to regard it as another example of a methazonic acid reaction. The reaction of nitroacetone with o-aminobenz-aldehyde leads to 2-methyl-3-nitroquinoline derivatives.84... 

If the N-oxides contain methyl groups, these can be chlorinated as discussed previously. Thus, 2-methyl-3-nitropyridine-A/-oxide (76) is converted by phosphorus pentachloride-phosphorus oxychloride to 6% of 77 and 8% of 78 (78T3445). More complicated is the reaction of 5-nitroquinoline-A-oxide (79) with POCI3 to give 35% of 80, 20% of 81, as... 

C10H8N2O3 5-methyl-4-nitroquinoline-1-oxide 14094-43-0 385.15 32.968 2 18890 C10H9NO N-hydroxy-1 -aminonaphthalene 607-30-7 533.60 47.122 2... 

Most activity in this area has centered around the isolation of so-called pseudo-bases (82) in which the cyano group is replaced by a hydroxy group. Thus the pseudo-base is obtained, in addition to the normal Reissert compound, from S-nitroisoquinoline, " 3-methyl-5-nitroisoquinoline, 6-nitroquinoline, and phthalazine. Heating the pseudo-bases in alcohol gives rise to the ethers 83. A discussion of some of the chemistry and properties of the pseudo-bases has appeared. The formation of the pseudo-bases can be suppressed and that of the Reissert compounds increased by the use of a phase-transfer catalyst. Pseudo-bases have also been obtained in attempts to form Reissert compounds from 1,6-naphthyridine and 4,6-phenanthroline. 2-Phenyl-1,2,3-thiadiazole and benzoyl chloride in the presence of cyanide gave 84 and imidazo[l,5-a]pyrazines with acid chloride gave 85 in reactions analogous to the pseudo-base formation. 

Inhibition of azoxymethane (AOM) induced colon tumors Inhibition of Af-methyl-A -nitrosourea (NMU) induced colon tumors Inhibition ofiV-diethylnitrosamine (DEN)/phenobarbital (PB) induced hepatic tumors Inhibition of sponateneous hepatoma development in C3H/HeNCrj mice Inhibition of 4-(methylnitrosoamino)-l-(3-pyridyl)-I-butanone (NNK) induced lung tumors Inhibition of 4-nitroquinoline-W-oxide (4-NQO)/glycerol induced pulmonaiy tumors Inhibition of NMU induced mammary tumors... 

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