4- Trifluoromethyl quinoline, preparation

N-Methoxy-N-methyl-2,8-bis(trifluoromethyl)-quinoline-4-carboxamide was prepared using synthetic methodology reported by Thiesen et al (J. Org. 

The addition of an aniline to an unsaturated trifluoromethyl ketone 437 or 438 provides a facile preparation of an enaminone 439. In polyphosphoric acid (PPA), this cyclizes to a 4-trifluoromethyl quinoline 440, Scheme 121 (89TL6173 90TL2689). 

Various trifluoromethylated quinolines also can be prepared in good yield by the liquid-phase fluorination of the corresponding trichloromethyl- derivatives using anhydrous HF and antimony pentafluoride (chloride) as a catalyst. 

Kobayashi, Y. Kumadaki, I Taguchi, S. Organic fluorine compounds. VI. Preparations and reactions of (trifluoromethyl)quinoline 7V-oxide. Chem. Pharm. Bull. 1969, 77(11), 2335-2339. 

A similar approach has been used to prepare triazoles 11 and 12, with good antifungal activity against Aspergillus flavus, Aspergillus fumigatus, Candida albicans, Penicillium marneffei, and Trichophyton mentagrophytes, from 4-azido-8-(trifluoromethyl) quinoline 7 [7]. 

An efficient synthetic sequence for the preparation of 2,4-b/s(trifluoromethyl)furan was developed by R. Filler and co-workers. " The potassium enolate of ethyl 4,4,4-trifluoroacetate was reacted with 3-bromo-1,1,1-trifluoroacetate in DMSO to afford 2,4-bis (trifluormethyl)-4-hydroxydihydro-3-furoate as a result of O-alkylation. Interestingly, under these conditions usually C-alkylation is preferred. Next, dehydration was performed to give the corresponding 2,4-bis (trifluoromethyl)-3-furoate in good yield. Finally, decarboxylation by heating with quinoline and CUSO4 yielded the target furan in excellent yield. 

An efficient method to prepare l /f-spiro-[indoline-3,3 -quinoline]-2, 4 -diones and their trifluoromethylated products was developed hy Wang and co-workers in 2014. The reaction proceeds via a palladium-catalyzed Sono-gashira coupling-Wacker-type ojqqjalladation-cyclization cascade reaction sequence. The amount of water in the reaction system played an important role in the in situ trifluoromethylation reaction, and the trifluoromethylation exhibited excellent molecular self-induced stereoselectivity. 

The Cu" complexes can be prepared directly from trifluoromethyl substituted 1,2-dihalobenzenes in the course of Rosemund-Braun reaction with copper(I) cyanide (Scheme 25). Thus, reaction of 3-, 4-trifluoromethyl and 3,5-difluoromethyl substituted 1,2-dichlorobenzenes 102a-c with CuCN in quinoline (Qn) leads to Cu" complexes of a- or 3-tetrafluoromethyl- or a,p -octatrifluoromethyl-phthalocyanines 103a-c [71],... 

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