2,8-Bis(trifluoromethyl)-4-quinolinol synthesis

Yield:35853-41-9 91%

Reaction Conditions:

with polyphosphoric acid at 150; for 3 h;

Steps:

1 4.1.1. 2,8-bis(trifluoromethyl)quinolin-4-ol (19)

To a solution of polyphosphoric acid (637.7 mmol) in 2-trifluoromethylaniline (77.6 mmol) was added ethyl 4,4,4-trifluoroacetoacetate(77.7 mmol). The reaction mixture was stirred for3 h at 150 °C. Completion of the reaction was monitored by TLC. After,the reaction mixture was poured into iced distilled water slowly withvigorous stirring to form yellow precipitate. The precipitate was vacuumfiltered and washed with cold distilled water to give yellow solidin 91% yield. m.p 128-130 °C; 1H NMR (400 MHZ; DMSO-d6, ppm): δ7.30 (s, 1H, H-3); 7.80 (t, 1H, H-6; J=7.9 Hz); 8.28 (d, 1H, H-5;J=7.2 Hz); 8.52 (d, 1H, H-7, J=8.2 Hz); 13C NMR (100 MHz, DMSO-d6, ppm): δ 101.0 (C-3); 119.9 (C-4a); 121.9 (C-6); 122.6 (q, C-9,J=273 Hz); 125.3 (q, C-10, J=276 Hz); 127.3 (C-7); 130.0 (q, C-8,J=58 Hz); 144.5 (C-5); 148.4 (q, C-2, J=67 Hz); 163.3 (C-4); 19FNMR (376 MHZ; DMSO-d6, ppm): δ -58.98 (s, 3F; F-10); -67.03 (s,3F; F-9).

References:

da Silva, Renata M.R.J.;Gandi, Marilia O.;Mendon?a, Jorge S.;Carvalho, Alcione S.;Coutinho, Julia Penna;Aguiar, Anna C.C.;Krettli, Antoniana U.;Boechat, Nubia [Bioorganic and Medicinal Chemistry,2019,vol. 27,# 6,p. 1002 - 1008]