6- Chloro-8-nitroquinoline

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. 

By the same procedure the submitters have prepared 6-ethoxy-8-nitroquinoline in 70% yield, 8-methoxy-6-nitroquino-line in 68% yield, 6-chloro-8-nitroquinoline in 75% yield, and 6-methoxy-5-bromo-8-nitroquinoline in 69% yield from the properly substituted aromatic amines. 

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). 

A few comments on the polar effects of the substituents reported in Tables IX—XI are now relevant. With the exception of 4-chloro-5-nitroquinoline (see Section IV, C, l,c), they involve only positions not subject to primary steric effects. The relations to the reaction center are of the conjugative cata, amphi) as well as of the non-conjugative class meta, epi, pros) as shown in Chart 3 by structures 45 and 46. 

The order NO2 > Cl, which is known for the reactions of nitro-activated aromatic compounds, is also found for pyridine and quinoline derivatives. In the reaction of 2-chloro-4-nitroquinoline with methoxide ion, only the 4-methoxide derivative is formed, as shown by gas-chromatography, whereas 2,4-dichloroquinoline yields a mixture of the isomeric chloro-methoxy derivatives in comparable amounts. ... 

In 2-chloro-8-nitroquinoline (196), where resonance activation by the nitro group in the adjoining ring is possible, the chloro group is rapidly (10 min) displaced in boiling aqueous acid (cf. Table XI, p. 338). 

In a similar way, 3-amino-1,2,4-triazino[6,5-c]quinoline 4-oxides 127 were synthesized by the reaction of 4-chloro-3-nitroquinoline 128 with guanidine, followed by the cyclization of intermediate arylguanidines under basic conditions (81JHC1537). 

Reaction of 4-chloro-3-nitroquinoline 131 with guanidine or its deriva-... 

Electrophilic chlorination of quinoline under neutral conditions occurs in the orientation order 3 > 6 > 8. Hammett ct+ values predict an order for electrophilic substitution of 5 > 8 = 6 > 3. The reactivity order can be affected by substitution of an electron-withdrawing group in the benzene ring, which directs the chlorination to the pyridine ring. Thus, NCS in acetic acid or sulfuryl chloride in o-dichlorobenzene converts 8-nitroquinoline into 3-chloro-8-nitroquinoline in high yield (91M935). 

C9H5CIN203 5-chloro-4-nitroquinoline-1-oxide 14076-19-8 25.00 1.5169 2 15924 C9H60S2 di-2-thienylrnethanone 704-38-1 25.00 1.3236 2... 

C9H5CIN203 3>chloro-4 nitroquinoline-1-oxide 14100-52-8 405.90 34.922 2 16003 C9H7F302 a,a,a-trifluoro-p-tolyl)acetic acid 32857-62-8 476.15 41.597 2... 

As already mentioned in Section III,B> the volatile amines can be replaced by the corresponding formamides or phosphoramides. Thus, 2-chloro-5-nitroquinoline (80) affords, on heating in DMF, the corresponding 2-dimethylamino-5-nitroquinoline (104) in 94% yield with evolution of carbon monoxide and hydrochloric acid. The less reactive 2-chloro-quinoline gives 2-dimethylaminoquinoline in 76% yield (69CC38). 8-Amino-4-chloro-6-methoxyquinoline (105) furnishes analogously the 8-amino-4-dimethylamino-6-methoxyquinoline (106) in 65% yield (69CC38). 

A number of methods, based on [3+3] fragments, exploit the reactions of nitroaromatic compounds, donating the C-C-N fragment into the formed 1,2,4-triazine ring, with guanidine, which provides the N-C-N triad of atoms. This approach is illustrated by cyclizations of 2-fluoronitrobenzenes or 4-chloro-3-nitroquinoline into the corresponding... 

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