Nitroquinolines, amination

The synthesis can be carried out with most aromatic amines and is usually termed the Skraup reaction. The nitrobenzene is frequently replaced by arsenic acid, as in the prep)aration of 8-nitroquinoline from o-nitroanUine ... 

Amination of heterocyclic nitro compounds such as nitroquinolines, nitroisoquinolines, or nitropyridines can be carried out by means of a liquid ammonia-KMn04 system, which has been studied by Wozniak and coworkers (Eq. 9.44). Frontier molecular orbital calculation can predict the reactivity and regioselectivity of this amination.75 In a similar way, nitroquinolines are methylaminated with a liquid methylamine solution of KMn04.76... 

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. 

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). 

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. 

An important use of the traditional Skraup synthesis is to make 6-methoxy-8-nitroquinoline from an aromatic amine with only one free ortho position, glycerol, the usual concentrated sulfuric acid, and the oxidant arsenic pentoxide. Though the reported procedure uses 588 grams of As2Os, which might disconcert many chemists, it works well and the product can be turned into other quinolines by reduction of the nitro group, diazotization, and nucleophilic substitution (Chapter 23). 

Low valent species of transition metals (Groups IVB, VB and VIB) have found widespread use in the reduction of nitro compounds. Chromium(II) chloride, titanium(III) chloride and vanadium(II) sulfate readily reduce aromatic nitro compounds to arylamines. Chromium(II) chloride also reduces nitrobenzene and nitroquinoline to the corresponding amines in excellent yields. ... 

C10H8N2O3 7-methyi-4-nitroquinoline-1 -oxide 14753-13-0 385.15 32.968 2 18892 C10H9NO 2-naphthylhydroxyl amine 613-47-8 533.60 47.122 2... 

Tondys, H., Van der Plas, H. C., Wozniak, M. a-Adduct formation in liquid ammonia. Part 41. On the Chichibabin amination of quinoline and some nitroquinolines. J. Heterocyd. Chem. 1985, 22, 353-355. 

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). 

An alternative method for the preparation of benz[c]azepines and their pyrido analogues is the treatment of nitronaphthalenes and nitroquinolines with dimethyl phosphate under basic conditions <85CC1792, 91J0C1283>. Thus, treatment of 2-nitronapthalene or 6-nitroquinoline with secondary amines and sodium methoxide affords the phosphonates (250 X = CH or N) whereas 1-nitro-naphthalene and 5-nitro- or 8-nitroquinoline form a mixture of the tautomers (251 X and Y = CH or N) and (252 X and Y = CH or N). 

In the series of azaaromatics pyridine appears to possess the least electron deficiency and cannot be aminated under these conditirms. In contrast, diazines, triazines, tetrazines, quinolines, quinoxalines, quinazolines, naphthiridines, polyazaaromatic compounds, and their nitro derivatives are able to undergo oxidative amination. Moreover, amination of highly Jt-deficient triazines, tetrazines, 3-nitropyridine, 3-nitroquinoline, etc. is possible to perform without KNH2, since ammonia itself serves as nucleophile in such cases (Scheme 6). However, the more electron deficiency of an azine substrate, the less regioselectivity of the reaction. Oxidative amination of 3-nitrop3ridine in Uquid ammonia with potassium permanganate affords a mixture of 2-amino-3-nitro- (33%), 4-amino-3-nitro- (24%), and... 

The aza group activation effect in the oxidative amination of azines is less than that of the nitro group. As an illustration the reaction of 4-nitroquinoline and liquid ammonia in the presence of KMn04 produced 3-amino-4-nitroquinoline only in 86% yield [52]. Oxidative amination of 5-nitroquinoline gave 6-amino derivative in... 

Nitroquinoline, 435 8-Nitroquinoline, 435 4-Nitroquinoline N-oxide, 437 Nitrosamine, 156, 203-220, 398 A -Nitrosoanatabine, 204 -Nitrosobis(2-oxopropyl)amine, 204 -Nitrosodibenzylamine, 214 Nitrosodiethanolamine, 204 N-Nitroso group, 414 N-Nitroso-2- hydioxymorpholine, 216 N-Nitrosomorpholine, 205, 214, 216 N -Nitrosonomicotine, 204, 205, 214, 217-220 N -Nitrosonomicotine 1-N-oxide, 217 Nitrosophenol, 38... 

Aliphatic and aromatic nitro compounds are reduced at relatively positive potentials via the hydroxylamines to the corresponding amines. The carcinogenic 4-nitroquinoline-/V-oxide is determined by DPP in the presence of 4-hydroxyam-inoquinoline-/V-oxide and 4-aminoquinoline-/V-oxide via the reduction of the nitro group [79]. Nitrazepam, parathion, nitrofurantoin, and the ni-troimidazoles in blood plasma or urine are also determined via the reduction of the respective nitro groups. 

Ogawa, Y., Iwasaki, S., and Okuda, S., Photochemical aromatic hydroxylation by aromatic amine N-oxides, remarkable solvent effect on the NlH-shift, Tetrahedron Lett., 22, 3637, 1981. Botchaway, S.W., Chakrabarti, S., and Makrigiorgios, G.M., Novel visible and ultraviolet light photogeneration of hydroxyl radicals by 2-methyl-4-nitroquinoline N-oxide (MNO) and 4,4 -dinitro-(2,2 )bipyridyl N,N -dioxide (DBD), Photochem. Photobiol, 67, 635, 1998. 

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