Oxidation of quinoline

Ochiai and Ohta have used lead tetraacetate in benzene to convert aromatic iV-oxides (67) to the corresponding acetylated hydroxamic acids (68). Similar oxidation of quinoline and isoquinoline JV-oxides... 

This enzyme [EC 1.2.3.1] catalyzes the reaction of an aldehyde with water and dioxygen to produce a carboxylic acid and hydrogen peroxide. The enzyme uses both heme and molybdenum as cofactors. In addition, the enzyme can also catalyze the oxidation of quinoline and pyridine derivatives. In some systems this enzyme may be identical with xanthine oxidase. 

Oxidation of quinoline fused thiadiazoles occurs selectively at the quinoline nitrogen to provide the quinoline-Ai-oxide (78) in 70% yield <86IJC(B)271>. 

Oxidation of quinoline and isoquinoline under vigorous conditions with potassium permanganate results in oxidative degradation of the benzo-fused ring and formation of pyridine-2,3- and -3,4-dicarboxylic acid respectively. As expected, the presence of electron-donating substituents facilitates the reaction while electron-withdrawing substituents make oxidation much more difficult. Apart from A-oxide formation, little study has been devoted to the oxidation of other benzo-fused 7r-deficient systems. 

Radical attack on isoquinoline, as either free base or isoquinolinium cation, always occurs at position 1 and the method is not suitable for the preparation of benzo ring-substituted products. The same can be said of radical attack on the JV-oxides of quinoline and isoquinoline. 

Problem 20.36 Which dicarboxylic acid is formed on oxidation of quinoline The pyridine ring is more stable than the benzene ring [Problem 20.19(ft)J. 

Aldehyde oxidase, a non-microsomal enzyme discussed in more detail below, may also be involved in the oxidation of quinoline to give 2-hydroxyquinoline (Fig. 4.14). The heterocyclic phthalazine ring in the drug hydralazine is oxidized by the microsomal enzymes to phthalazinone. The mechanism, which may involve nitrogen oxidation, is possibly involved in the toxicity of this drug (see chap. 7). Again, other enzymes may also be involved (Fig. 4.15). 

Deoxygenation of N-oxides,4 TiCl4 -NaBH4 (1 2) in DME reduces the N-oxide of pyridine and mcthylpyridines (picolines) to the corresponding heterocycles in high yield. However the N-oxide of quinolines and isoquinolines is reduced further to dihydro derivatives of the hetcrocyclcs. Pyridine, quinoline, and isoquinoline themselves are not reduced by this low-valent titanium species. Reduction of heterocyclic N-oxides with TiCI, has been reported (6, 588). 

An efficient procedure for the reduction of pyridine iV-oxides to piperidines using ammonium formate and palladium on carbon has been developed (Equation 98) <2001JOC5264>. The reaction conditions are mild and can also be applied to the iV-oxides of quinoline and isoquinoline. 

Valentine RL, Wang HCA. Iron oxide surface catalyzed oxidation of quinoline by hydrogen peroxide. J Environ Eng 1998 124 31-38. 

A number of different Ar-oxides have been investigated polaro-graphically, such as the A-oxides of quinoline,252 acridine,244 pyra-zine,254 quinoxaline,243 phenazine,246 and adenine,248 and the influence of substituents has been discussed. 

Anodic oxidation of quinoline at a platinum anode in 75% sulfuric acid yields quinolinic acid (77%) [269] other quinolines bearing substituents in the hetero ring in the 3-position may do similarly, whereas some 2- and 4-substituted derivatives form tar [261]. 

A number of different A-oxides have been investigated polarographically, such as N-oxides of quinoline [421], acridine [422], pyrazine [423], benzimidazole [424], quinoxaline [415], phenazine [416], and adenine [425], and the influence of substituents was discussed. 

The classic SsAi substitution of activated aryl halides by protected cyanohydrin anions provides substituted benzophenones. Another procedure for the arylation of protected cyanohydrin anions involves the use of aromatic substrates activated as their rr-chromium tricarbonyl complexes. - Addition of the anion of (32) to the 1,3-dimethoxybenzene complex, for example, leads principally to the meta-suh-stituted isomer (33 equation 20). Preferential meta regioselectivity is also noted with other -rr-chromium tricarbonyl complexes of arenes. Other arylations of cyanohydrin anions include interesting but synthetically limited additions at the a-position of quinoline N-oxides. In a similar manner, cyanohydrin carbonates of aromatic aldehydes react with A -oxides of quinoline and isoquinoline. ... 

Dioarbopyridic acids—C H3N(C00H)i.—The six acids whose existence is indicated by theory are all known. Among them are quinolinic acid, formed by tlie oxidation of quinolin, and cin-chomeric acid, produced by the oxidation of cinehonin, cinchoni-din or quinin. 

A -Oxides of quinolines and isoquinolines also undergo this type of reaction [56]. 

A number of publications also describe the air oxidation of the same pyridine substrates in the presence of cupric nitrate. Extensive work has also been reported on the fixed or fluidized bed vapor phase of alkylpyridines using vanadium catalysts. " The intermediate aldehydes can be isolated, but usually the conditions are set to minimize this side reaction. Vanadates, molybdates, and tin salts of these two oxyacids are also described as efTective catalysts in the high temperature oxidation of quinolines and isoquinolines. " ... 

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