Brominated 4-(Trifluoromethyl)pyrimidines
FULL PAPER
5-Chloro-4-(trifluoromethyl)pyrimidin-2(1H)-one (13): A solution of
4-(trifluoromethyl)pyrimidin-2(1H)-one (4; 25 g, 0.15 mol), sulfuryl
chloride (20 g, 12 mL, 0.15 mol) and iron() chloride (2.4 g,
15 mmol) in glacial acetic acid (0.15 L) was heated at 80 °C for 2 h
before the solvent was evaporated. The residue was triturated with
water (0.10 mL), collected by filtration, washed with water (2 ϫ
0.20 L) again and dried in a desiccator. Colorless prisms (from ethyl
acetate). Yield: 23.8 g (80%). M.p. 177Ϫ178 °C (reprod.). 1H
NMR*: δ ϭ 8.71 (s, 1 H) ppm. 13C NMR*: δ ϭ 160.7 (s), 158.6
(s), 155.6 (q, J ϭ 35 Hz), 120.6 (q, J ϭ 277 Hz), 115.3 (s) ppm.
MS: m/z (%) ϭ 119 (10) [Mϩ ϩ 1], 198 (21) [Mϩ], 170 (28), 131
(43), 129 (100), 101 (15). C5H2ClF3N2O (198.53): calcd. C 30.25,
H 1.02; found C 30.28, H 0.79.
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2,5-Dichloro-4-(trifluoromethyl)pyrimidine (15): Prepared as de-
scribed for pyrimidine 7 from 5-chloro-4-(trifluoromethyl)pyrimi-
din-2(1H)-one (13; 20 g, 0.10 mol). Colorless oil. Yield: 17.6 g
(81%). B.p. 40Ϫ41 °C/5 Torr. n2D0 ϭ 1.4691. d420 ϭ 1.606. 1H NMR:
δ ϭ 8.86 (s, 1 H). 13C NMR: δ ϭ 162.1 (s), 159.0 (s), 153.8 (q, J ϭ
37 Hz), 127.8 (s), 119.2 (q, J ϭ 276 Hz), 115.7 (s). MS: m/z (%) ϭ
217 (45) [Mϩ ϩ 1], 216 (100) [Mϩ], 189 (7), 147 (12), 128 (12).
C5HCl2F3N2 (216.98): calcd. C 27.68, H 0.46; found C 27.69, H
0.25.
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5-Iodo-4-(trifluoromethyl)pyrimidin-2(1H)-one (14): A solution of 4-
(trifluoromethyl)pyrimidin-2(1H)-one[15] (4; 25 g, 0.15 mol) and
iodine chloride (26 g, 0.15 mol) in glacial acetic acid (0.15 L) were
heated at 80 °C for 2 h, then the solvent was evaporated. The resi-
due was triturated with water (0.10 L), collected by filtration,
washed with water (2 ϫ 0.20 L) again and dried in a desiccator.
Colorless platelets (from ethyl acetate). Yield: 24.8 g (60%). M.p.
[14]
[15]
[16]
[17]
1
214Ϫ216 °C (dec.). H NMR*: δ ϭ 8.81 (s, 1 H) ppm. 13C NMR*
: δ ϭ 164.0 (s), 160.1 (q, J ϭ 35 Hz), 158.8 (s), 137.4(s), 120.2 (q,
J ϭ 278 Hz) ppm. MS: m/z (%) ϭ 308 (8), 291 (17) [Mϩ ϩ 1], 290
(100) [Mϩ], 239 (50), 221 (36), 163 (13), 127 (38). C5H2F3IN2O
(289.98): calcd. C 20.71, H 0.70; found C 20.84, H 0.64.
[18]
[19]
[20]
2-Chloro-5-iodo-4-(trifluoromethyl)pyrimidine (16): Prepared as de-
scribed for pyrimidine 7 from 5-iodo-4-(trifluoromethyl)pyrimidin-
2(1H)-one (14; 22 g, 75 mmol). Colorless oil. Yield: 17.8 g (77%).
B.p. 66Ϫ67 °C/2 Torr. n2D0 ϭ 1.5493. d420 ϭ 2.086. 1H NMR: δ ϭ
9.1 (s, 1 H) ppm. 13C NMR: δ ϭ 170.4 (s), 160.6 (s), 158.4 (q, J ϭ
36 Hz), 119.3 (q, J ϭ 272 Hz), 85.8 (s) ppm. MS: m/z (%) ϭ 309
(50) [Mϩ ϩ 1], 308 (100) [Mϩ], 239 (5), 220 (18), 178 (10), 161 (18),
127 (66). C5HClF3IN2 (308.42): calcd. C 19.46, H 0.33; found C
19.36, H 0.33.
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2,4-Dibromo-6-(trifluoromethyl)pyrimidine (18): Prepared as de-
[24]
scribed for pyrimidine
1
from 6-(trifluoromethy)pyrimidine-
[21]
2,4(1H,3H)-dione
(17; 9 g, 50 mmol) with a stoichiometric
[25]
[26]
[27]
[28]
amount of phosphorus tribromide (29 g, 0.10 mol). Colorless
prisms (from methanol). Yield: 12.1 g (79%). M.p. 81Ϫ83 °C (re-
1
prod.). H NMR: δ ϭ 7.83 (s, 1 H) ppm. 13C NMR: δ ϭ 157.5 (q,
J ϭ 38 Hz), 155.5 (s), 152.5 (s), 120.8 (s), 118.9 (q, J ϭ 278 Hz)
ppm. MS: m/z (%) ϭ 305 (67) [Mϩ ϩ 1], 304 (47) [Mϩ], 285 (26),
225 (58), 131 (100), 122 (92), 95 (88). C5HBr2F3N2 (305.88): calcd.
C 19.63, H 0.33; found C 19.40, H 0.34.
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Acknowledgments
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This work was financially supported by the Schweizerische
Nationalfonds zur Förderung der wissenschaftlichen Forschung,
Bern (grant 20-55Ј303-98) and the Bundesamt für Bildung und
Wissenschaft, Bern (grant 97.0083 linked to the TMR project
FMRXCT-970129).
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2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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