6- Amino-5-nitroquinoline

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... 

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). 

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. 

Primaquine Primaquine, 8-[(4-amino-l-methylbutyryl)amino]-6-methoxyquinoline (37.1.2.4), is made from 6-methoxy-8-nitroquinoline (37.1.2.1), which is synthesized in a Skraup reaction from 4-methoxy-2-nitroaniline and glycerol in the presence of sulfuric acid. The nitro group in this compound is reduced to make 6-methoxy-8-aminoquinoline (37.1.2.2). Alkylating the amino group with 4-bromo-l-phthalimidopentane gives 8-[(4-phthalimido-l-methylbutyryl)amino]-6-methoxyquinoline (37.1.2.3), the hydrazi-nolysis of which removes the phthalimide protection, giving primaqnine [28,29]. 

The introduction of methoxy substituents increases the ease of removal of trityl groups under acid conditions, but also decreases the selectivity for the primary hydroxyl group [377]. As a compromise, the monomethoxytrityl and dimethoxy-trityl groups found widespread use for the protection of primary positions of glycosides (see, e.g. Ref. [378]) and, especially for the OH-5 function of nucleosides [377]. The use of 6-nitroquinoline instead of pyridine was described [379] to improve the selectivity of monomethoxytritylation of nucleosides and nucleotides bearing free amino groups. A general and rapid procedure was developed for the preparation and isolation of 5 -0-dimethoxy trityl derivatives [380]. 

The Sandmeyer procedure for the synthesis of aryl halides from arylamines has been applied, with modification, to the conversion of 5- and 8-aminoquinolines to the iodo and bromo derivative. 8-Aminoquinoline is converted to 8-bromoquinoline in good yield on treatment with /-butyl nitrite in the presence of CuBr in acetonitrile at 60 °C <2003JOC5123> and 5-amino-6-nitroquinoline is converted to the 5-iodo derivative under equally mild conditions using potassium nitrite and copper iodide in DMSO at 60 °C <2005JOC2445>. 

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). 

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... 

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