O. Lefebvre, M. Marull, M. Schlosser
FULL PAPER
1.0 Hz, 1 H), 7.43 (d, J ϭ 8.5 Hz, 1 H), 7.32 (td, J ϭ 7.7, 1.0 Hz,
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m.p. 248Ϫ251 °C (from ethanol; reprod.); yield: 4.77 g (21%). H
1 H), 6.98 (s, 1 H) ppm. 13C NMR (D3CSOCD3): δ ϭ 160.0, 139.8, NMR (D3CSOCD3): δ ϭ 7.68 (d, J ϭ 7.3 Hz, 1 H), 7.60 (d, J ϭ
136.6 (q, J ϭ 31 Hz), 131.7, 124.3, 122.8, 122.6 (q, J ϭ 277 Hz),
7.0 Hz, 1 H), 7.34 (t, J ϭ 7.6 Hz, 1 H), 7.11 (s, 1 H), 2.61 (s, 3 H)
122.0 (q, J ϭ 5 Hz), 116.5, 113.1 ppm. MS (c.i.): m/z (%) ϭ 231 ppm. 13C NMR (D3CSOCD3): δ ϭ 161.3, 139.0, 137.9 (q, J ϭ
(27) [Mϩ ϩ 18], 214 (100) [Mϩ ϩ 1], 213 (34) [Mϩ], 185 (8), 166 31 Hz), 133.8, 125.9, 123.7 (q, J ϭ 272 Hz), 123.5, 123.0, 122.6,
(2). C10H6F3NO (213.16): calcd. C 56.35, H 2.84; found C 56.19,
H 3.00.
114.1, 18.8 ppm. MS (c.i.): m/z (%) ϭ 245 (0) [Mϩ ϩ 18], 228 (100)
[Mϩ ϩ 1], 227 (35), 198 (2), 130 (1). C11H8F3NO (227.15): calcd.
C 58.16, H 3.55, N 6.17; found C 57.93, H 3.29, N 6.18.
6-Methyl-4-trifluoromethyl-2(1H)-quinolinone (1b): Analogously,
using p-toluidine (11 g, 0.10 mol); colorless needles; m.p. 257Ϫ269
°C (from ethanol; reprod.); yield: 7.27 g (32%). 1H NMR
(D3CSOCD3): δ ϭ 7.6 (m, 2 H), 7.47 (d, J ϭ 8.5 Hz, 1 H), 7.07 (s,
1 H), 2.54 (s, 3 H) ppm. 13C NMR (D3CSOCD3): δ ϭ 160.9, 138.9,
137.3 (q, J ϭ 33 Hz), 134.9, 133.3, 133.1, 123.7, 123.5 (q, J ϭ
277 Hz), 117.4, 114.0, 21.7 ppm. MS (c.i.): m/z (%) ϭ 246 (0) [Mϩ
ϩ 18], 228 (100) [Mϩ ϩ 1], 198 (4). C11H8F3NO (227.15): calcd. C
58.16, H 3.55, N 6.17; found C 58.09, H 3.55, N 6.12.
4-Trifluoromethyl-Substituted 2-Bromoquinolines 2
2-Bromo-4-(trifluoromethyl)quinoline (2a): At 60 °C, quinolinone 1a
(11 g, 50 mmol) was added to an excess of phosphorus oxybromide
(29 g, 0.10 mol). The mixture was heated at 140 °C for 2 h before
being poured onto ice (0.20 L). The precipitated brown mass was
collected and dissolved in methanol (0.20 L) containing charcoal
(3 g). The slurry was stirred at 25 °C for 1 h before being filtered
through a pad of diatomaceous earth. The residue left after evapor-
ation of the solvent was crystallized from methanol; colorless
needles; m.p. 56Ϫ57 °C (after sublimation); yield: 9.11 g (66%). 1H
NMR: δ ϭ 8.15 (d, J ϭ 8.5 Hz, 1 H), 8.11 (d, J ϭ 8.5 Hz, 1 H),
7.83 (m, 2 H), 7.71 (ddd, J ϭ 8.4, 7.0, 1.3 Hz, 1 H) ppm. 13C NMR:
δ ϭ 149.5, 140.6, 136.2 (q, J ϭ 33 Hz), 131.4, 129.6, 128.6, 124.1,
123.1 (q, J ϭ 6 Hz), 122.5 (q, J ϭ 277 Hz), 121.9 ppm. MS (c.i.):
m/z (%) ϭ 294 (0) [Mϩ ϩ 18], 277 (100) [Mϩ ϩ 1], 276 (82) [Mϩ],
213 (14), 196 (67), 176 (47). C10H5BrF3N (276.05): calcd. C 43.51,
H 1.83; found C 43.43, H 1.71.
6-Fluoro-4-trifluoromethyl-2(1H)-quinolinone (1c): Analogously,
using p-fluoroaniline (9.5 mL, 11 g, 0.10 mol); colorless needles;
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m.p. 252Ϫ253 °C (from ethanol; decomp.); yield: 2.54 g (11%). H
NMR (D3CSOCD3): δ ϭ 7.59 (td, J ϭ 9.2, 2.6 Hz, 1 H), 7.49 (dd,
J ϭ 9.1, 4.9 Hz, 1 H), 7.41 (d, J ϭ 9.5 Hz, 1 H), 7.08 (s, 1 H) ppm.
13C NMR (D3CSOCD3): δ ϭ 159.6, 156.4 (d, J ϭ 238 Hz), 136.5,
135.7 (q, J ϭ 34 Hz), 123.1 (d, J ϭ 5 Hz), 121.9 (q, J ϭ 275 Hz),
120.0 (d, J ϭ 25 Hz), 118.4 (d, J ϭ 18 Hz), 113.4 (d, J ϭ 9 Hz),
109.3 (d, J ϭ 25 Hz) ppm. MS (c.i.): m/z (%) ϭ 249 (0) [Mϩ ϩ 18],
232 (40) [Mϩ ϩ 1], 231 (100) [Mϩ], 203 (26), 184 (19), 107 (9).
C10H5F4NO (231.15): calcd. C 51.96, H 2.18, N 6.06; found C
52.03, H 2.10, N 6.11.
2-Bromo-6-methyl-4-(trifluoromethyl)quinoline (2b): Analogously,
from quinolinone 1b (11 g, 50 mmol); colorless needles; m.p. 97Ϫ99
°C (from methanol); yield: 8.56 g (59%). 1H NMR: δ ϭ 8.03 (d,
J ϭ 8.5 Hz, 1 H), 7.83 (s, 1 H), 7.76 (s, 1 H), 7.65 (dd, J ϭ 8.5,
1.7 Hz, 1 H), 2.57 (s, 3 H) ppm. 13C NMR: δ ϭ 147.8, 139.3, 139.2,
135.7 (qr, J ϭ 32 Hz), 133.6, 129.0, 122.9, 122.4 (qr, J ϭ 276 Hz),
121.7, 22.0 ppm. MS (c.i.): m/z (%) ϭ 308 (0) [Mϩ ϩ 18], 291 (38)
[Mϩ ϩ 1], 290 (100) [Mϩ], 227 (11), 212 (5). C11H7BrF3N (290.06):
calcd. C 44.55, H 2.43, N 4.83; found C 45.15, H 2.32, N 4.89.
7-Methyl-4-trifluoromethyl-2(1H)-quinolinone (1d): Analogously,
using m-toluidine (11 mL, 11 g, 0.10 mol); colorless needles; m.p.
210Ϫ213 °C (from ethanol; reprod.); yield: 6.59 g (29%). 1H NMR
(D3CSOCD3): δ ϭ 7.59 (d, J ϭ 8.6 Hz, 1 H), 7.22 (s, 1 H), 7.14
(d, J ϭ 8.2 Hz, 1 H), 6.89 (s, 1 H), 2.41 (s, 3 H) ppm. 13C NMR
(D3CSOCD3): δ ϭ 160.1, 142.0, 139.7, 136.2 (q, J ϭ 31 Hz), 124.2,
123.8, 122.5 (q, J ϭ 276 Hz), 120.5 (q, J ϭ 5 Hz), 116.0, 110.9,
21.1 ppm. MS (c.i.): m/z (%) ϭ 245 (0) [Mϩ ϩ 18], 228 (100) [Mϩ
ϩ 1], 198 (7), 130 (3), 102 (1). C11H8F3NO (227.15): calcd. C 58.16,
H 3.55, N 6.17; found C 58.06, H 3.64, N 6.31.
2-Bromo-6-fluoro-4-(trifluoromethyl)quinoline (2c): Analogously,
from quinolinone 1c (12 g, 50 mmol); colorless needles; m.p.
1
108Ϫ109 °C (from methanol); yield: 8.67 g (59%). H NMR: δ ϭ
8.16 (dd, J ϭ 9.3, 5.4 Hz, 1 H), 7.85 (s, 1 H), 7.73 (dm, J ϭ 9.4 Hz,
1 H), 7.61 (ddd, J ϭ 9.2, 7.9, 2.7 Hz, 1 H) ppm. 13C NMR: δ ϭ
161.4 (d, J ϭ 257 Hz), 146.5, 139.8, 136.1 (qr, J ϭ 35 Hz), 132.2
(qr, J ϭ 5 Hz), 124.0 (d, J ϭ 25 Hz), 122.8, 122.2 (qr, J ϭ 275 Hz),
121.8 (d, J ϭ 26 Hz), 108.7 (d, J ϭ 25 Hz) ppm. MS (c.i.): m/z
(%) ϭ 312 (0) [Mϩ ϩ 18], 295 (62) [Mϩ ϩ 1], 294 (100) [Mϩ], 276
(2), 214 (5), 145 (2). C10H4BrF4N (294.04): calcd. C 40.85, H 1.37;
found C 40.82, H 1.81.
7-Methoxy-4-trifluoromethyl-2(1H)-quinolinone (1e): Analogously,
using p-anisidine (11 mL, 12 g, 0.10 mol); tiny yellowish needles;
m.p. 219Ϫ222 °C (from ethanol; reprod.); yield: 7.29 g (30%). H
1
NMR (D3CSOCD3): δ ϭ 7.72 (dm, J ϭ 8.0 Hz, 1 H), 7.05 (dd,
J ϭ 9.5, 2.5 Hz, 1 H), 7.04 (s, 1 H), 6.89 (s, 1 H), 3.94 (s, 3 H)
ppm. 13C NMR (D3CSOCD3): δ ϭ 162.9, 161.7, 143.0, 137.5 (q,
J ϭ 31 Hz), 126.8, 123.8 (q, J ϭ 278 Hz), 119.4 (q, J ϭ 6 Hz),
113.3, 108.1, 100.2, 56.7 ppm. MS (c.i.): m/z (%) ϭ 261 (0) [Mϩ
ϩ
18], 244 (100) [Mϩ ϩ 1]. C11H8F3NO2 (243.14): calcd. C 54.34, H
2-Bromo-7-methyl-4-(trifluoromethyl)quinoline (2d): Analogously,
from quinolinone 1d (11 g, 50 mmol); colorless needles; m.p. 49Ϫ51
°C (from methanol); yield: 8.99 g (62%). 1H NMR: δ ϭ 8.00 (d,
J ϭ 8.9 Hz, 1 H), 7.92 (s, 1 H), 7.75 (s, 1 H), 7.55 (d, J ϭ 8.9 Hz,
1 H), 2.60 (s, 3 H) ppm. 13C NMR: δ ϭ 149.7, 142.3, 140.7, 136.2
(qr, J ϭ 32 Hz), 131.0, 128.7, 123.7, 122.7 (qr, J ϭ 276 Hz), 122.1,
120.9, 21.6 ppm. MS (c.i.): m/z (%) ϭ 308 (0) [Mϩ ϩ 18], 290 (100)
[Mϩ], 227 (7), 190 (3). C11H7BrF3N (290.06): calcd. C 45.55, H
2.43, N 4.83; found C 45.55, H 2.23, N 4.90.
3.32, N 5.76; found C 54.46, H 3.32, N 5.88.
7-Fluoro-4-trifluoromethyl-2(1H)-quinolinone (1f): Analogously,
using m-fluoroaniline (11 mL, 11 g, 0.10 mol); tiny colorless
needles; m.p. 166Ϫ167 °C (from ethanol; decomp.); yield: 7.16 g
(31%). 1H NMR (D3CSOCD3): δ ϭ 7.87 (tm, J ϭ 8.0 Hz, 1 H),
7.30 (m, 2 H), 7.05 (s, 1 H) ppm. 13C NMR (D3CSOCD3): δ ϭ
164.2 (d, J ϭ 247 Hz), 161.2, 142.6 (d, J ϭ 12 Hz), 137.4 (d, J ϭ
31 Hz), 128.0 (d, J ϭ 10 Hz), 123.2 (q, J ϭ 267 Hz), 121.5, 112.4
(d, J ϭ 23 Hz), 111.2, 103.1 (d, J ϭ 26 Hz) ppm. MS (c.i.): m/z
(%) ϭ 249 (0) [Mϩ ϩ 18], 232 (100) [Mϩ ϩ 1], 231 (88) [Mϩ], 203
(19), 184 (8). C10H5F4NO (231.10): calcd. C 51.97, H 2.18, N 6.06;
found C 52.03, H 1.95, N 6.18.
2-Bromo-7-methoxy-4-(trifluoromethyl)quinoline (2e): Analogously,
from quinolinone 1e (12 g, 50 mmol); colorless needles; m.p. 76Ϫ78
1
°C (from methanol); yield: 8.11 g (53%). H NMR: δ ϭ 7.96 (dd,
J ϭ 9.2, 2.0 Hz, 1 H), 7.66 (s, 1 H), 7.44 (d, J ϭ 2.3 Hz, 1 H), 7.31
(dd, J ϭ 9.2, 2.8 Hz, 1 H), 3.95 (s, 3 H) ppm. 13C NMR: δ ϭ 161.9,
151.4, 141.0, 136.1 (qr, J ϭ 32 Hz), 125.1, 122.5 (qr, J ϭ 282 Hz),
8-Methyl-4-trifluoromethyl-2(1H)-quinolinone (1g): Analogously
using o-toluidine (11 mL, 11 g, 0.10 mol); tiny colorless needles;
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2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2003, 2115Ϫ2121