Quinoline-8-carboxylic acid

This is an example of the Doebner synthesis of quinoline-4-carboxylic acids (cinchoninic acids) the reaction consists in the condensation of an aromatic amine with pyruvic acid and an aldehj de. The mechanism is probably similar to that given for the Doebner-Miller sj nthesis of quinaldiiie (Section V,2), involving the intermediate formation of a dihydroquinoline derivative, which is subsequently dehydrogenated by the Schiff s base derived from the aromatic amine and aldehyde. 

Cinchoninic acid—see Quinoline-4-carboxylic acid Cinenic acid... 

Quinoline-4-carboxylic acid, 3-hydroxy-Pfitzinger synthesis, 2, 446 Quinoline-4-carboxylic acid, 2-methyl-synthesis, 2, 475... 

Friedlander synthesis, 2, 444 as antipyretic, 1, 172 Quinoline-4-carboxylic acids amination, 2, 236 Beyer synthesis, 2, 475 Pfitzinger synthesis, 2, 446... 

Preparation of 8-Methyl-2-phenyl-quinoline-4-carboxylic acid (32)... 

The Pfitzinger reaction describes the condensation of an o-aminophenylglyoxylic acid 16 (which can be generated in situ from an isatin IS) with 2 results in a quinoline-4-carboxylic acid (17), which is the subject of its own chapter in this book. ... 

The Pfitzinger reaction entails the synthesis of quinoline-4-carboxylic acids 2 via condensation of isatic acids formed from isatins 1 and a-methylene carbonyl compounds in the presence of strong aqueous bases. Subsequent decarboxylation can afford the corresponding quinolines. " ... 

Esterification of the corresponding quinoline-4-carboxylic acid gave the ester 511 which upon reaction with pyrrolidine in THE gave the amide 512. Its phosphorylation and reaction with 513 in presence of KOBu afforded 514 which is useful in the treatment of anxiety, sleep disorders, panic states, convulsions, muscle disorders (95WOP9514020) and chronic neurodegen-erative diseases (97WOP9700074) (Scheme 87). 

Bauer G, F Lingens (1992) Microbial metabolism of quinoline and related compounds XV. Quinoline-4-carboxylic acid oxidoreductase from Agrobacterum spec. IB a molybdenum-containing enzyme. Biol Chem Hoppe-Seyler 370 1183-1189. 

The Pfitzinger reaction of isatins with a-methylene carbonyl compounds is widely used for the synthesis of substituted quinoline-4-carboxylic acids. Ivachtchenko and colleagues have recently reported on the Pfitzinger reaction in a series of 5-sulfa-moylisatins (Scheme 6.239) [422]. Treatment of 5-sulfamoylisatins with diethyl mal-... 

Quinoid-type chromophoric structures, reactions of, 21 36-37 Quinoline (QI), 12 723, 725-726 soluble dyes, 7 373t Quinoline-4-carboxylic acids, 21 190 Quinoline derivatives, 21 196-214 Quinoline-derived drugs, 21 197-198t Quinoline dyes, 21 196 Quinoline, formation of, 21 109. See also Quinolines... 

Recent studies with quinoline-4-carboxylic acid angiotensin II receptor antagonists have confirmed the interest of (oxodioxolyl)methyl esters as prodrugs with improved oral bioavailability and efficacy in laboratory animals [79], Olmesartan, another angiotensin II receptor antagonist, has also been derivatized to a (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl carboxylate designated as olmesartan medoxomil [80], In this case, both human serum albumin and arylesterase (presumably EC 3.1.1.2, although paraoxonase cannot be excluded) were shown to be involved in hydrolysis. 

Three-component coupling of an aniline, pyruvic acid, and an aldehyde to provide a quinoline-4-carboxylic acid. 

Although aldehydes have not been used, oximes have been used to prepare 3-substituted quinoline-4-carboxylic acids.614 The dioxime of... 

Pfitzinger Reaction. Quinoline-4-carboxylic acids are easily prepared by the condensation of isatin with carbonyl compounds. The products may be decarboxylated to the corresponding quinolines. 

Published data on the Pfitzinger reaction and its modifications, leading to quinoline-4-carboxylic acids, are reviewed, analyzed, and classified. 

The condensation of isatin 7 with 2-acetyl-4-phenylquinoline (sodium hydroxide or potassium hydroxide, water, boiling, 1 h) gave an 80% yield of 2-(4-phenyl-2-quinolinyl)quinoline-4-carboxylic acid [114, 115],... 

Isatinates, obtained from the alkaline hydrolysis of isatin derivatives, are the precursors of the quinoline-4-carboxylic acids. These compounds are prepared by the Pfitzinger reaction from isatins in the presence of enolizable keto compounds in strongly alkaline medium, such as 8N KOH. In these solutions, isatinates condense with the keto compound and subsequently cyclize to the quinoline products. Recently, a modified procedure has been described, using acidic conditions. This methodology was subsequently applied to a concise manner for the preparation of derivatives of camptothecin, a topoisomerase I inhibitor23 (Scheme 115). 

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