3- chloroquinoline-8-carboxylate

Chloro-2-hydroxypyridine-3-carboxylate is a terminal metabolite in the degradation of 3-chloroquinoline-8-carboxylate, but can be degraded by Mycobacterium sp. strain BA to chlorofumarate by reactions analogous to those described above for pyridine carboxylates (Figure 10.18) (Tibbies et al. 1989a). 

Tibbies PE, R Muller, F Lingens (1989b) Microbial metabolism of quinoline and related compounds. III. Degradation of 3-chloroquinoline-8-carboxylic acid by Pseudomonas spec. EKIII. Biol Chem Hoppe-Seyler 310 1191-1196. 

Chloroquinolines are reactive groupings due to electron-deficient carbon to which the halogen is attached. This carbon is electron-deficient due to the combined electron-withdrawing effects of the chlorine substituent and the quinoline nitrogen. The electrophilic carbon is thus able to react readily with nucleophiles present in the body. The impact of this grouping on a molecule is illustrated by 6-chloro-4-oxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate (Figure 8.28). In contrast to many related compounds (chromone-carboxylates) lacking the chloroquinoline, 6-chloro-4-oxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate is excreted as a... 

Fig. 8.28 Structure of 6-chloro-4-0X0-10-propyl-4 H-pyrano[3,2-g]quino-line-2,8-dicarboxylate which, in contrast to many related compounds (chromone-carboxylates) lacking the chloroquinoline, is excreted as a glutathione conjugate.

A convenient synthesis of thieno[2,3-6]quinoline (Scheme 111) (76ZN(B)1297,76ZN(B)1685, 77JCS(P1)2024) utilizes the readily available methyl 2-oxo-3-vinyl-l//-quinoIin-4-carboxylate (380) as starting material. Treatment of (380) with phosphorus oxychloride yields the chloroquinoline which on addition of bromine gives a trihalo compound. The cyclization to (381) is effected with thiourea in boiling ethanol. Elimination of the methoxycarbonyl group yields thieno[2,3-6]quinoline as colorless needles with m.p. 107-108 °C, which can be characterized as the picrate with m.p. 213-214 °C. 

Reaction with 6,7-disubstituted 4-chloroquinoline-S-carboxylates.7 Quinolines of this type (1) are converted into the corresponding 4-hydroxyquinolines (2) when heated... 

Pyrazolo[3,4-Z)]pyridines, the 7-chloro-6-fluoro-2,4-dimethylquinoline and its mercapto-thiadiazolyl or oxadiazolyl quinolines 21 were prepared via Diels-Alder reaction conversion of methyl 2-(3-oxo-3-phenylpropenylamino)benzoate into 3-benzoyl-l.S -quinolin-4-one 22 . A mixture of aniline derivatives and malonic ester gave a variety of 3-aryl-4-hydroxyquinolin-2(l//)-ones 23. Condensation of isatins with ketones afforded quinoline-4-carboxylic acids. 2-Aryl-l,2,3,4-tetrahydro-4-quinolinones 22 and carbazolylquinolone were also prepared. The substitution of 2-chloroquinoline gave the 2-substituted quinolines. Basic alumina has catalyzed the C-C bond formation between 2-hydroxy-1,4-naphthoquinone and 2-chloroquinoline derivative to give 21. Reaction of organic halides with 8-hydroxyquinolines gave the respective ethers. The azodye derivatives of 21 were prepared in the absence of solvent. Silica gel catalyzed the formation of 2-ketomethylquinolines from reaction of 2-methylquinolines with acyl chlorides. 

Needles from EtOH or AcOH. M.p. above 320°. Mod. sol. hot EtOH, hot AcOH. Spar, sol. hot H 0, E O. Brownish-red col. with FeCl, in BTjO. PCI5—> 2-chloroquinoline-3-carboxylic acid. 

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