Quinoline, trifluoromethyl-, amination

Aromatic primary amines are not only binucleophiles at the amino group, but they also exhibit the properties of C,N-binucleophiles. Their reactions with internal perfluoroolefins lead to quinoline derivatives (98JFC(88)169, 94JCS(CC)134, 98T4949). Thus the reaction of aniline with 2//-heptafluorobut-2-ene yields phenyl(2-trifluoromethylquinolin-4-yl) amine (00ZOR109) when the reaction is carried out with the tetrafluoro-ethylene trimer, it leads to 2-trifluoromethyl-3-(l-N-phenylimino-2,2,2-trifluoroethyl)-4-(N-phenylamino)quinoline (98JFC(88)169). 

Hydroxy-2-(trifluoromethyl)pyridine derivatives 80 (Scheme 31) were linked [53] to the acetamide moiety in the usual way. Pyridyloxy-acetamides 81 smoothly rearranged into the respective 4-aminopyridines 82 when heated with potassium carbonate in DMF at 150 °C. Acid hydrolysis provided amines 83. In a similar way, hydroxy-quinolines and hydroxy-acridines were transformed into the respective amines [50,54]. 

Trifluoromethyl-3,l-benzoxazine-4-ones (255) react rapidly with enamines (256) at low temperatures to quinoline-8-carboxylic acids (258) and a secondary amine. Nucleophilic attack of (256) on (255) has been assumed, forming an intermediate vinamidine (257) which immediately undergoes cyclization103 ... 

Several primary and secondary amines have been used in the 5 2 ring opening of 2,8-bis(trifluoromethyl)quinoline-4-oxirane at the least-substituted carbon of the epoxide, giving possible antimalarial dmgs. Yields range from 35 to 98% with... 

Amination of 5,7-difluoro- and 5,7,8-trifluoroquinoline, 5,7-difluoro-8-chloro-quinoline and 6-trifluoromethyl-5,7,8-trifluoroquinoline leads to the formation of rather complicated mixtures of monoaminoquinolines [101]. The reaction of hepta-fluoroquinoline with S-nncleophiles (HS , PhS , MeS , PrS h BuS) is very indicative, since it demonstrates a high regioselectivity, resulting in displac ent of halogen at the position 4 [102]. 

Zhu M, Fu W, Xun C, Xun C, Deng D, Ji B (2012) An efficient synthesis of 2-trifluoromethyl quinolines via gold-catalyzed cycUzation of trifluoromethylated propargyl-amines. J Fluorine Chem 135 195-199... 

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