Methoxy-8-nitroquinoline

Methoxy-6-nitroquinoline, 27, 52 6-Methoxy-8-nitroquinoline, 27, 48 6-Methoxy-8-nitroquinoline sulfate, 27,... 

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. ... 

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]. 

Thus, interaction of 3-nitroquinoline 242 with potassium cyanide in methanol furnishes a mixture of isoxazole 243 and 3-methoxy-4-cyanoquinoline 244 (Scheme 71) (68CPB1700, 69CPB140). Isomeric nitroquinolines 207, 245-247 enter a similar transformation (the arrow indicates the place of primary nucleophilic attack). 

The product may also be recrystallized from hot ethylene dichloride using 300 ml. of solvent for each 100 g. The recovery is 80-90% of 6-methoxy-8-nitroquinoline melting at 160-161°. 

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. 

Methoxy-8-nitroquinoline was first obtained by Schule-mann and coworkers 1 by a modification of the Skraup reaction. Various other modifications of this reaction have been used by Magidson,2 Fourncau,8 Altman/ tirahmachari,8 Misani and Bo-... 

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). 

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