4-(trifluoromethyl)quinoline derivatives

Under carefully controlled conditions, Et 4,4,4-trifluoroacetoacetate (Et 4,4,4-trifluoro-3-oxobutanoate) can be condensed with anilines and subsequently cyclized to give 4-trifluoromethyl-2-quinolinones although only in poor yield. Heating these products with phosphoryl tribromide affords 2-bromo-4-(trifluoromethyl)quinolines which can be converted into 4-(trifluoromethyl)quinolines by redn., 4-trifluoromethyl-2-quinolinecarboxylic acids by permutational halogen/metal exchange followed by carboxylation, and 2-bromo-4-trifluoromethyl-3-quinolinecarboxylic acids by consecutive treatment with lithium diisopropylamide and dry ice. Debromination of the acids makes 4-trifluoromethyl-3-quinolinecarboxylic acids available. As at any time 2-trifluoromethyl-4-quinolinones may form instead of the expected 4-trifluoromethyl-2-quinolinone isomers , the structures have to be assigned on the basis of unequivocal NMR spectral criteria. [on SciFinder (R)]