3- Nitroquinoline

Twenty milliliters of nitric acid (sp. gr. 1.5) is added to 50 g. (0.39 mole) of quinoline at 0°. The solid formed is added in five portions to 50 ml. of concentrated sulfuric acid at 0°, and 10 ml. of fuming sulfuric acid (sp. gr. 2.0) is introduced after the addition of each portion. The mixture is diluted with water and neutralized with sodium hydroxide the precipitated oil is separated and dissolved in a large volume of water to which a small amount of nitric acid has been added. After filtration the solution is saturated with sodium acetate and allowed to stand. The precipitated 5-nitroquinoline is recrystallized from petroleum ether to give 32 g. (54%) of white needles melting at 72°. Nine grams (13%) of 8-nitroquinoline (p. 235) may be isolated by complete neutralization of the nitric acid solution. 

A mixture of 116 g. of arsenic acid, 220 g. of concentrated sulfuric acid, 240 g. of glycerol, and 112 g. (0.81 mole) of p-nitroaniline is heated carefully under a reflux condenser until the onset of an exothermic reaction. When the rate of reflux has decreased considerably, heat is again applied and the reflux temperature is maintained for 2.5-3 hours. The mixture is diluted with water, allowed to stand overnight, and filtered, and the filtrate is made alkaline with sodium hydroxide. The precipitated solid is separated, dissolved in hot dilute hydrochloric acid, and treated with activated carbon. Filtration followed by saturation of the filtrate with ammonia gas precipitates crystalline 6-nitroquinoline. Recrystallization from a mixture of ethanol and water gives 98 g. (70%) of product melting at 148-149°. 

8-Nitroquinoline, m.p. 88-89°, is prepared in similar manner and 74% yield from a mixture of 15.5 g. of arsenic acid, 100 g. of concentrated sulfuric acid, 110 g. of glycerol, and 50 g. (0.36 mole) of o-nitroaniline. 

---

These systems nitrate aromatie eompounds by a proeess of electro-philie substitution, the eharacter of whieh is now understood in some detail ( 6.1). It should be noted, however, that some of them ean eause nitration and various other reactions by less well understood processes. Among sueh nitrations that of nitration via nitrosation is especially important when the aromatic substrate is a reactive one ( 4.3). In reaetion with lithium nitrate in aeetie anhydride, or with fuming nitrie aeid, quinoline gives a small yield of 3-nitroquinoline this untypieal orientation (ef. 10.4.2 ) may be a eonsequenee of nitration following nucleophilic addition. ... 

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). 

QH AsNOjj 121-19-7) see Acetarsol 4-hydroxy-3-nitroquinoline (C HfiN203 50332-66-6) see Imiquimod 8-hydroxy-5-nitrosoquinoline (CijHf N202 3565-26-2) see Nitroxoline... 

Reaction of 4-chloro-3-nitroquinoline 131 with guanidine or its deriva-... 

Acids and Lewis acids react with quinoline at the basic nitrogen atom to form quinolinium salts, and there is a question over the nature of the substrate for electrophilic attack, i.e. is it quinoline or the quinolinium cation The answer is not a simple one and appears to depend upon the reagents and reaction conditions. Thus, whereas acetyl nitrate at 20 °C gives mainly 3-nitroquinoline (Scheme 3.2), fuming nitric acid in concentrated sulfuric acid containing sulfur trioxide at 15-20 °C yields a mixture of 5-nitroquinoline (35%) and 8-nitroquinoline (43%) (Scheme 3.3). In the case of acetyl nitrate, the reaction may proceed by the 1,4-addition of the reagent to quinoline, followed by electrophilic attack upon the 1,4-dihydro derivative. 

Pyruvic acid and isatins gave quinoline-2,4-dicarboxylic acids.16 36 Use of malonic acid with isatins gave 2-quinolone-4-carboxylic acids.169 620 Nitromethane and isatin with 50% potassium hydroxide gave 3-nitroquinoline-4-carboxylic acid.623... 

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). 

A series of l,2,4-triazino[5,6-c]quinolines have been prepared via a common route. Thus, 4-[fi-(ethoxymethylene)hydrazino]-3-nitroquinoline (244), prepared from 4-hydrazino-3-nitroquinoline (243) by reaction with triethyl orthoformate, was hydrogenated in ethanol over a palladium catalyst to give the dihydro compound (184) (96%). Dehydrogenation yielded the desired compound (185) (90%) (Scheme 19) <73GEP(0)2322394>. 

Nitroquinoline derivatives have been prepared by cyclization routes from type 2 or type 3 synthons. 

Isatin has been reported to yield 3-nitrocinchoninic acid (92 R = C02H) with nitromethane in aqueous KOH.83 Although this seems like the use of a type 1 synthon, it is more appropriate to regard it as another example of a methazonic acid reaction. The reaction of nitroacetone with o-aminobenz-aldehyde leads to 2-methyl-3-nitroquinoline derivatives.84... 

---