Quinolines, nitro-, nitration

Quinoline, 5-nitro-oxidation, 2, 210 synthesis, 2, 318 Quinoline, 6-nitro-nitration, 2, 318 Quinoline, 7-nitro-nitration, 2, 318 synthesis, 2, 318 Quinoline, 8-nitro-... 

Den Hertog and Overhoff - observed that when pyridine in sulfuric acid is added to molten potassium sodium nitrate the 3-nitro derivative is formed at 300°C, whereas at 450°C 2-nitropyridme is the main product. The latter is probably a free-radical process. Schorigin and Toptschiew obtained 7-nitroquinoline by the action of nitrogen peroxide on quinoline at 100°C, possibly through the homolytic addition of NOa. Laville and Waters reported that during the decomposition of pernitrous acid in aqueous acetic acid, quinoline is nitrated in the 6- and 7-positions. They considered that the reaction proceeds as shown in Scheme 3. 

Little is known quantitatively about substituent effects in the nitration of derivatives of azanaphthalenes. In preparative experiments 4-hydroxy-quinoline, -cinnoline, and -quinazoline give the 6- and 8-nitro compounds, but with nitric acid alone 4-hydroxyquinoline and 2,4-di-hydroxyquinoline react at With nitric acid, 4-hydroxycinnoline... 

Ewins has synthesised both substances from m-methoxybenzoic acid, which on nitration gave 2-nitro-3-methoxybenzoic acid, and this, on reduction and treatment with methyl iodide, yielded damasceninic acid, which, by esterification with methyl alcohol, furnished damascenine. Kaufmann and Rothlen found that the additive product of 8-methoxy-quinoline and methyl sulphate, on oxidation with permanganate, yields formyldamasceninic acid, MeO. CgH3(NMe. CHO). COOH, which can be transformed into damasceninic acid by warming with dilute hydrochloric acid. ... 

The nitration of l,2,5-selenadiazolo[3,4-/] quinoline 77 with benzoyl nitrate affords the 8-nitro derivative 78, whereas methylation with methyl iodide or methyl sulfate afforded the corresponding 6-pyridinium methiodide 79 or methosulfate 80, respectively (Scheme 29). The pyridinium salt 80 was submitted to oxidation with potassium hexacyanoferrate and provided 7-oxo-6,7-dihydro derivative 81 or, by reaction of pyridinium salt 79 with phenylmagnesium bromide, the 7-phenyl-6,7-dihydro derivative 82. Nucleophilic substitution of the methiodide 79 with potassium cyanide resulted in the formation of 9-cyano-6,9-dihydroderivative 83, which can be oxidized by iodine to 9-cyano-l,2,5-selenadiazolo [3,4-/]quinoline methiodide 84. All the reactions proceeded in moderate yields (81IJC648). 

Nitration of quinoline 144 leads to the nitro derivative 145. Reduction of the nitro group leads to... 

Nitration of pyridines in other than nitric or sulfuric acids is of little interest here because either no reaction or N-nitration takes place (see Section 2.05.2.10). However, pyridine 1-oxide is considerably more reactive and treatment with benzoyl nitrate ultimately leads to the 3-nitro derivative (Scheme 25) (60CPB28). Annelation of a benzene ring bestows greater reactivity on the 3-position in quinoline, compared with pyridine, and reaction with nitric acid in acetic anhydride furnishes the 3-nitro derivative (ca. 6%) (Scheme 26). This isomer has also been obtained, again at low yield (6-10%), by treatment of quinoline with tetranitratotitanium(IV) in carbon tetrachloride (74JCS(P1)1751>. Nitration of benzo analogues of pyridine occurs much more readily in the benzene ring, and Chapter 2.06 should be consulted for these reactions. 

Benzo[/]quinoline (13 R=H) on nitration at -15 °C gives 7-nitrobenzo[/]quinoline (40%) (13 R = N02) together with smaller amounts of the 10- (13%) and 9-nitro derivatives (9%). At 0 °C the 7,9-dinitro derivative is obtained. Nitration of benzo[/]quinoline AT-oxide gives 7-nitrobenzo[/]quinoline Af-oxide. 

Nitraminopyridines, mentioned above, are intermediates formed during the nitration of aminopyridines. An example (96) from the quinoline series is shown in Scheme 84. The nitramines undergo acid-catalyzed rearrangement to ring nitro compounds (97). 

The first nitration of 1,10-phenanthroline in one of the pyridine rings has been accomplished by the use of fuming nitric acid in acetic anhydride.252 In this way 3-nitro-1,10-phenanthroline was obtained in very low yield. The mechanism proposed for the nitration is the same as that previously proposed for the similar nitration of quinoline.277 4,5-Diazafluorenone was again a coproduct. 

Substituents on the benzene rings exert their usual influence on the orientation and ease of electrophilic substitution reactions. For example, further nitration (HN03-H2S04-S03) of nitroquino-lines occurs meta to the nitro group as shown in diagrams (593) and (594). Friedel-Crafts acylation of 8-methoxyquinoline succeeds (cf. 595) although this reaction fails with quinoline itself. 

Nitration of ethyl l-oxo-l//-pyrimido[l,2-a]quinoline-2-carboxylate (38, R = Et) in 98% sulfuric acid with 100% nitric acid at 0°C for 15 min, then at room temperature for 90 min afforded the 5-nitro derivative (74MIP1). 

Mononitration of 3-phenylquinoline (mixed acid) yields 3-(4nitrophe-nyDquinoline as the only isolable product (64%). Further nitration gives two products, the main one is 5-nitro-3-(4-nitrophenyl)quinoline (65%), also obtained by the nitration of 5-nitro-3-phenylquinoIine, and the second (10%) was not established (58JOC271). 4-Phenylquinoline yields the 2-, 3-, and 4-nitrophenyl products in the ratio 60 30 5 (1887CB624). 

Little is known quantitatively about substituent effects in the nitration of derivatives of azanaphthalenes. In preparative experiments 4-hydroxy-quinoline, -cinnoline, and -quinazoline give the 6- and 8-nitro compounds, but with nitric acid alone 4-hydroxyquinoline and 2,4-di-hydroxyquinoline react at C(3).31 With nitric acid, 4-hydroxycinnoline still gives mainly 4-hydroxy-6-nitrocinnoline, but some of the 3-nitro compound can also be isolated.81 51 The change of orientation with reagent could be due to a change to free-base nitration in the more weakly acidic medium, or to the occurrence in nitric acid of nitration via nitrosation.31... 

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-hydroxy-quinoline) 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 i-methyl-4-quinolone the total yield of nitro-compounds was not high (table 10.3). 

In recent years, the reactivities of thieno[2,3-c]pyridine and its fused analogs have received considerable attention. Nitration of thieno[2,3-c]quinoline 5-N-oxide (225) gives rise to 1-nitro derivative 226 (1989CS305), whereas bromination affords a mixture of bromide 227 and dibromide 228 (1989CS309). 

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