An improved access to 4-trifluoromethyl-2(1H)-quinolinones: The "watering protocol"

Condensation of anilines with Et 4,4,4-trifluoroacetoacetate to afford the corresponding 4,4,4-trifluoro-3-oxobutaneanilides, precursors to 4-(trifluoromethyl)-2-quinolinones, can be favored and the competing condensation to produce the Et 4,4,4-trifluoro-3-(phenylimino)butanoate, the precursor to 2-(trifluoromethyl)-4-quinolinones, avoided if water is occasionally added to the reaction mixt. while ethanol is continuously removed by distn. The 4,4,4-trifluoro-3-oxobutaneanilides also form selectively when 4,4,4-trifluoroacetoacetyl chloride is allowed to react with anilines. The cyclization of the anilides has to be accomplished under carefully controlled conditions. The resulting 4-(trifluoromethyl)-2-quinolinones can be converted into 4-(trifluoromethyl)quinolines, 4-(trifluoromethyl)-2-quinolinecarboxylic acids, and 2-bromo-4-(trifluoromethyl)quinolines, the last of which may in turn be converted into 2-bromo-4-(trifluoromethyl)-3-quinolinecarboxylic acids and eventually 4-trifluoromethyl-3-quinolinecarboxylic acids. [on SciFinder (R)]

Published in:
European Journal of Organic Chemistry, 1, 54-63
CAN 140:199185 27-17 Heterocyclic Compounds (One Hetero Atom) Institut de Chimie moleculaire et biologique,Ecole Polytechnique Federale, BCh,Lausanne,Switz. Journal 1434-193X written in English. 62-53-3 (Aniline); 95-51-2 (2-Chloroaniline); 95-53-4 (2-Methylaniline); 106-49-0 (4-Methylaniline); 108-44-1 (3-Methylaniline); 348-54-9 (2-Fluoroaniline); 371-40-4 (4-Fluoroaniline); 372-19-0 (3-Fluoroaniline); 372-31-6 (Ethyl 4,4,4-trifluoroacetoacetate); 461-82-5 (4-Trifluoromethoxyaniline); 536-90-3 (3-Methoxyaniline); 615-36-1 (2-Bromoaniline); 615-43-0 (2-Iodoaniline); 2261-53-2 (4,4,4-Trifluoroacetoacetyl chloride) Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of 4-trifluoromethyl-2(1H)-quinolinones); 836-31-7P; 1701-23-1P; 1828-96-2P; 25199-84-2P; 73496-31-8P; 328951-07-1P; 328955-68-6P; 328956-08-7P; 404597-27-9P; 590372-06-8P; 643734-90-1P; 643734-93-4P; 663191-92-2P; 663191-97-7P; 663192-00-5P; 663192-03-8P; 663192-06-1P; 663192-11-8P; 663192-13-0P; 663192-17-4P; 663192-22-1P; 663192-35-6P; 663192-66-3P; 663192-71-0P; 663193-19-9P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of 4-trifluoromethyl-2(1H)-quinolinones); 590372-08-0P; 663192-77-6P; 663192-84-5P; 663192-88-9P; 663192-94-7P; 663193-06-4P; 663193-12-2P; 663193-15-5P; 663193-23-5P; 663193-27-9P; 663193-30-4P; 663193-33-7P; 663193-35-9P; 663193-37-1P; 663193-39-3P; 663193-41-7P; 663193-43-9P; 663193-45-1P; 663193-47-3P; 663193-49-5P; 663193-51-9P; 663193-53-1P; 663193-55-3P; 663193-57-5P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of 4-trifluoromethyl-2(1H)-quinolinones)
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 Record created 2006-03-03, last modified 2018-01-27

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