Quinoline, 6-methoxy-8-nitro

METHOXY-8-NITRO QUIN OLINE (Quinoline, 6-methoxy-8-nitro-)... 

Quinoline, 4,7-dichloro-, 28, 38 Quinoline, 2,4-dimethyl-, 28, 49 Quinoline, 6-methoxy-8-nitro, 27, 48 Quinones, 22, 37... 

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 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. ... 

Under acidic conditions, the formation of a nearly 1 1 mixture of 5- and 7-substituted quinoline-3-carboxylates, with a slight excess of the former, was observed from the 3-chloro- and 3-methyl derivatives. The cycliza-tions of 3-nitro, 3-trifluoromethyl, and methoxy derivatives were carried out only in polyphosphate to give mainly the 7-substituted isomers. 

On cooling, the sulfate salt of the 6-methoxy-8-nitro-quinoline partially crystallizes from the reaction mixture. By stirring the mixture, the product comes down as a fine tan, microcrystalline precipitate. This can be isolated and crystallized, but it is more convenient to work it up in the form of the base. 

These methanol washings remove much of the impurities, especially small amounts of unreacted nitroanisidine, with a minimum loss of product. The solubility of 6-methoxy-8-nitro-quinoline in methanol at room temperature is 0.8 g. per 100 g. of solvent and at the boiling point is 4.1 g. per 100 g. of solvent. The solubility in chloroform, on the other hand, is 3.9 g. per 100 g. of solvent at room temperature and 14.2 g. at the boiling point. It is possible to obtain about 12 g. of product by working up these washings, but it is usually not worth the trouble. 

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). 

Substituent effects follow the general pattern of substituted benzene derivatives in that nitro, sulfonic acid, and carboxyalkyl groups deactivate the ring to further substitution, whereas amino and methoxy groups strongly activate, and methyl and chloro groups have little effect. Ridd383 has recently reviewed electrophilic substitutions on quinoline, pyridine, and imidazole. 

Indol l-Methoxycarbonyl-4-nitro-E6b/2, 1027 (NH - N-COOR) Quinolin 4-Hydroxy-6-methoxy-3-nitro- E7a, 319 (2-COOH-Ar-N = CH-CH2-N02)... 

Deady et al. used methyl 2-amino-3-formylbenzoate with o-methoxy-and o-nitro-phenylacetic acids, phenylpyruvic acid, and benzo[fc]thio-phen-2-one to prepare quinoline analogs (99SC4223, 00AJC143). 

The Doebner-von Miller reaction was used as a method of choice for the synthesis of several biological active quinoline compounds. The anti-malarial drug primaquine, which acts against the hepatic stage of plasmodia infection, was synthesized by a Skraup reaction fi om 4-methoxy-2-nitroaniline and glyceron in the presence of sulfiiric acid. The nitro group was then reduced and alkylated with 4-bromo-l-phthalimidopentane to provide the protected primaquine, which was deprotected by using hydrazine. ... 

A solution 1.5 g lran5-3- 2-[5-(4-methanesulfonylpiperazine-l-ylmethyl)-2-nitro-phenyl]vinyl -2-methoxyquinoline (3.10 mmol) in 15.5 mL P(OEt)3 was heated to 155°C for 2 h and the solvent was removed under reduced pressure. The residue was purified by flash silica gel chromatography to give 908 mg 2-methoxy-3-[5-[[4-(methysulfonyl)-l-piperazinyl]methyl]-l//-indol-2-yl]quinoline as a light yellow solid, in a yield of 62%, m.p. 197-198°C. 

Recently has been discovered that an oxoiso orphine derivative with an amino group at the position 6 called Lakshminine (Figure 7) (6-amino-l-aza-5-methoxy-7//-dibenzo[rfe,/ ]quinolin-7-one ) has presented an interesting antiproliferative activity. This rare natural product has now been synthesized in order to have sufficient amounts for biological testing, its 4-amino isomer, their 6- and 4-nitro precursors, the intermediate 5-methoxy-7//-dibenzo[Je,/z]quinolin-7-one, and the unsubstituted skeleton were tested against normal human fibroblasts and three human solid tumor cell line s. Only the 4-nitro precursor showed marginal antiproliferative activity [34],... 

---