8- Nitroquinoline, reaction with

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). 

In the Meisenheimer reaction of quinoline 1-oxides chlorine atoms usually enter the 2-and 4-positions, but not exclusively. 2,4-Dibromoquinoline 1-oxide was 6-chlorinated (57MI1), and the 5- and 6-nitroquinoline 1-oxides were 3-chlorinated to some extent (44JOC302). This reaction with phosphoryl chloride-phosphorus pentachloride has also been used in the preparation of chlorinated phenanthrolines (88YZ1148). 

Electronegative groups do not invariably prevent nuclear bromination, but reaction conditions must be much more severe, and the orientation of substitution may be affected by the substituent. Thus 6-nitroquinoline was brominated in sulfuric acid at 100°C to give the 8-bromo product (71) in 51% yield 8-methyl-5-nitroquinoline gave a 69% yield of the 7-bromo derivative (72) under similar conditions, whereas 7-chloroquinoline was transformed into the 5-bromo product (93%) (88CHE892) (Scheme 35). In a sealed tube reaction with bromine, 8-nitroquinoline gave a mixture... 

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

These systems nitrate aromatic compounds by a process of electrophilic substitution, the character of which is now understood in some detail ( 6.1). It should be noted, however, that some of them can cause nitration and various other reactions by less well understood processes. Among such nitrations that of nitration via nitrosation is especially important when the aromatic substrate is a reactive one ( 4.3). In reaction with lithium nitrate in acetic anhydride, or with fuming nitric acid, quinoline gives a small yield of 3-nitroquinoline this untypical orientation (cf. 10.4.246) may be a consequence of nitration following nucleophilic addition.5... 

Reaction of 5-R-l-nitronaphthalenes and 5-nitroquinoline 288 with a-chloropropyl-/Molylsulfone in NaOH/DMSO leads to oxazinones 289, although in diminished yields (Scheme 84) [86LAC69, 87LAC711],... 

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>. 

Trifluoromethylquinoline-N-oxide under similar conditions gave 4-cyano-3-trifluoromethylquinoline in 48% yield [91], while 4-nitroquinoline-N-oxide gave (31) on reaction with potassium cyanide and ethyl cyanoacetate [92]. 

Ried and his group have continued their work with benzo[6]thiophen derivatives, and have shown that they may be converted to a number of heterocycles [e.g. (267) and (268)] upon reaction with dicyclohexyl carbodi-imide and cyanamides. Some Japanese workers have followed up an earlier report concerning nitroquinolines with an interesting reaction in the naphthalene series. The potassium salt (269), which is formed from 2-nitronaphthalene cyclizes on treatment with HCl to give naphtho-l,3-oxazines (270), and these in turn can be further modified. 

Because 2-nitroquinoline and 4-nitroquinoline were no reactive in all the experiences development in this reaction conditions, the study started by testing the reactivity of 5-nitroquinoline 84 and 8-nitroquinoline 85, with the dienes 5,7, 8 and l-trimethylsyliloxy-1,3-butadiene 63. When 84 was heated with the less reactive isoprene 5 it gave as principal product the 5-(3-methyl-lH-pyrrolil)-quinoline 86, through the participation of the nitro group in a hetero DA process followed by a thermal rearrangement -hetero DA pathway-. (Cancian, et al, 2010)... 

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 ... 

A few comments on the polar effects of the substituents reported in Tables IX—XI are now relevant. With the exception of 4-chloro-5-nitroquinoline (see Section IV, C, l,c), they involve only positions not subject to primary steric effects. The relations to the reaction center are of the conjugative cata, amphi) as well as of the non-conjugative class meta, epi, pros) as shown in Chart 3 by structures 45 and 46. 

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. ... 

Various reactions of nitroquinolines with hydroxylamine in potassium hydroxide alkalinity afforded oxadiazoloquinolines besides the known aminonitroquinolines. l,2,5-Oxadiazolo[3,4-/]quinolines were obtained from the 5- or 6-nitroquinolines. The 7- and 8-nitroquinolines gave the appropriate l,2,5-oxadiazolo[3,4-/i]quino-lines. 

The key intermediate for the preparation of the 8-aminoquin-oline antimalarial agents is obtained by condensation of the substituted aniline, 90, with "dynamite-grade" glycerol in concentrated sulfuric acid. (The reaction may well follow some scheme such as that depicted below.) Ihe nitroquinoline obtained from... 

Likewise with 2-nitronaphthalcne (6), 1 //-2-benzazepin-l -yl phosphonates 7 are formed in good yields, and the method can also be used to synthesize pyridoazepines from nitroquinolines (see Section 3.2.1.4.1.5.). The reaction fails, however, with 2-substituted 1-nitronaphthalenes. 

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]. 

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. 

As part of a chemical study of the antibiotic X-537A, 1, the latter was treated with 5 equivalents of concentrated nitric acid in glacial acetic acid. The major product from this reaction was a dinitro derivative of 1 which, on treatment with dilute aqueous sodium hydroxide solution, gave a mixture of products one of which was shown to be 6-hydroxy-2,7-dimethyl-5-nitroquinoline. 

---