M. Schlosser, J.-N. Volle, F. Leroux, K. Schenk
FULL PAPER
(c.i.): m/z (%) ϭ 195 (21) [Mϩ ϩ 1], 194 (37) [Mϩ], 178 (7), 177
(100), 155 (23).
Treatment of the acid 16 (10 mmol) with ethereal diazomethane
gave the methyl ester as a colorless viscous oil; m.p. 21Ϫ23 °C; b.p.
60Ϫ61 °C/0.1 Torr; yield: 2.5 g (93%). 1H NMR: δ ϭ 8.12 (s, 1 H),
7.5 (m, 3 H), 7.4 (m, 2 H), 3.92 (s, 3 H) ppm. 19F NMR: δ ϭ Ϫ56.0
4-Bromo-1-methyl-3-trifluoromethyl-5-pyrazolecarboxylic Acid (15):
Prepared from 4-bromo-1-methyl-3-(trifluoromethyl)pyrazole (4;
4.6 g, 20 mmol) and lithium diisopropylamide (20 mmol) as de-
scribed above (see acid 12); colorless prisms; m.p. 194Ϫ196 °C
(from ethyl acetate and hexanes); yield: 4.9 g (90%). 1H NMR: δ ϭ
4.27 (s, 3 H) ppm. 19F NMR: δ ϭ Ϫ62.9 ppm. MS (c.i.): m/z (%) ϭ
275 (13) [Mϩ ϩ 1], 274 (100) [Mϩ], 273 (18), 272 (97), 271 (6), 255
(21). C6H4BrF3N2O2 (273.01): calcd. C 26.40, H 1.48; found C
26.15, H 1.08.
ppm. MS (c.i.): m/z (%) ϭ 288 (4) [Mϩ ϩ NH4], 272 (19) [Mϩ
ϩ
2], 2 71 (100) [Mϩ ϩ 1], 270 (23) [Mϩ], 239 (15). C12H9F3N2
(270.21): calcd. C 53.34, H 3.36; found C 53.41, H 3.15.
1-Phenyl-5-trifluoromethyl-4-pyrazolecarbaldehyde: 1-Phenyl-5-(tri-
fluoromethyl)pyrazole (5; 4.2 g, 20 mmol) was treated as described
in the preceding paragraph (see acid 16) but at the end N,N-di-
methylformamide (3.1 mL, 2.9 g, 40 mmol) was added rather than
carbon dioxide. At 25 °C, the mixture was poured into water (0.10
L) and extracted with diethyl ether (3 ϫ 50 mL). The combined
organic layers were concentrated, absorbed on silica gel (20 mL)
and eluted with a 1:9 (v/v) mixture of ethyl acetate and hexanes
from a column filled with more silica (0.20 L). Crystallization af-
forded small yellow cubes; m.p. 93Ϫ95 °C (from chloroform and
3. Transformation of Trifluoromethyl-Substituted 1-Arylpyrazoles
(E)-4,4,4-Trifluoro-2-phenylamino-2-butenenitrile (17): Diisopropyl-
amine (2.8 mL, 2.0 g, 20 mmol) and 1-phenyl-5-(trifluoromethyl)-
pyrazole (5; 4.2 g, 20 mmol) were added consecutively to a solution
of butyllithium (20 mmol) in tetrahydrofuran (25 mL) and hexanes
(15 mL) kept in a dry ice bath. After 6 h at Ϫ75 °C, the mixture
was allowed to reach 0 °C. It was concentrated, poured into water
(0.10 L) and extracted with diethyl ether (3 ϫ 50 mL). The com-
bined organic layers were washed with brine (2 ϫ 25 mL), dried
and the solvents evaporated. The residue was crystallized; yellow
stars; m.p. 97Ϫ99 °C (from chloroform and hexanes; yield: 3.2 g
(75%). 1H NMR: δ ϭ 7.45 (t, J ϭ 7.9 Hz, 2 H), 7.30 (t, J ϭ 7.5 Hz,
1 H), 7.20 (d, J ϭ 7.5 Hz, 2 H), 6.21 (br. s, 1 H), 4.76 (s, 1 H) ppm.
19F NMR: δ ϭ Ϫ67.9 ppm. MS (c.i.): m/z (%) ϭ 231 (13), 230
(100) [Mϩ ϩ NH4], 214 (11) [Mϩ ϩ 2], 2 13 (83) [Mϩ ϩ 1], 212
(47) [Mϩ]. C10H7F3N2 (212.17): calcd. C 56.61, H 3.33; found C
56.46, H 3.40.
1
hexanes); yield: 2.5 g (52%). H NMR: δ ϭ 10.15 (s, 1 H), 8.21 (s,
1 H), 7.5 (m, 5 H) ppm. 19F NMR: δ ϭ Ϫ55.2 ppm. MS (c.i.): m/
z (%) ϭ 241 (36) [Mϩ ϩ 1], 2 40 (100) [Mϩ], 239 (93) [Mϩ], 238
(14). C11H7F3N2O (240.18): calcd. C 55.01, H 2.94; found C 55.21,
H 2.62.
4-Iodo-1-phenyl-5-(trifluoromethyl)pyrazole: The iodo derivative
was prepared from 1-phenyl-5-(trifluoromethyl)pyrazole (5; 4.2 g,
20 mmol) using iodine (2.6 g, 20 mmol) instead of carbon dioxide
(see acid 16) or N,N-dimethylformamide (see preceding paragraph)
to intercept the organometallic intermediate. The product was isol-
ated by column chromatography (under identical conditions to
those reported in the preceding paragraph) as a colorless viscous
oil (after distillation); b.p. 73Ϫ75 °C/0.2 Torr; yield: 3.0 g (44%).
1H NMR: δ ϭ 7.75 (s, 1 H), 7.5 (m, 3 H), 7.4 (m, 2 H) ppm. 19F
Crystal Structure of Nitrile 17: The compound crystallized from a
NMR: δ ϭ Ϫ55.8 (s) ppm. MS (c.i.): m/z (%) ϭ 340 (15) [Mϩ
ϩ
chloroform/hexanes mixture in the orthorhombic space group
˚
2], 339 (65) [Mϩ ϩ1], 338 (46) [Mϩ], 213 (29). C10H6F3IN2
Pbn21. At Z ϭ 4, a ϭ 7.2381(14), b ϭ 7.525(2), c ϭ 17.556(4) A
and Mr
ϭ 212.18, the calculated density, ρcalc, became
(338.07): calcd. C 35.53, H 1.79; found C 35.28, H 1.65.
1.474 g·cmϪ1. The structure was solved by direct methods as imple-
mented in the program SIR97.[47] A total of 5393 reflections were
collected on a Stoe IPDS diffractometer using Mo-Kα radiation
2-(5-Trifluoromethyl-1-pyrazolyl)benzoic Acid (18): At Ϫ75 °C, tert-
butyllithium (40 mmol) in pentanes (25 mL) was added to 1-(2-
bromophenyl)-5-(trifluoromethyl)pyrazole (6; 5.8 g, 20 mmol) in
diethyl ether (50 mL). After 5 min, the mixture was poured onto
an excess of freshly crushed dry ice. The product was isolated as
described above (see acid 9); colorless stars; m.p. 121Ϫ123 °C (from
(λ ϭ 0.71073 A), µ ϭ 0.131 mmϪ1, no absorption correction being
˚
made. Using 2128 reflections with I Ն 2σ(I), the final full-matrix
least-squares refinement[48] of 136 variables converged to R1
ϭ
0.0563 {wR2 ϭ 0.0818, w ϭ [σ2(F2o)]Ϫ1}. The residual electron den-
1
ethyl acetate and hexanes); yield: 4.2 g (82%). H NMR: δ ϭ 8.14
sity fell in the range ∆ρ ϭ [Ϫ0.351,ϩ0.238] e·AϪ3. Hydrogen atoms
˚
(dd, J ϭ 7.8, 1.6 Hz, 1 H), 7.7 (m, 2 H), 7.63 (td, J ϭ 7.8, 1.4 Hz,
1 H), 7.48 (d, J ϭ 7.8 Hz, 1 H), 6.8 (m, 1 H) ppm. 19F NMR: δ ϭ
Ϫ59.2 (s) ppm. MS (c.i.): m/z (%) ϭ 270 (12) [Mϩ ϩ NH4], 257 (5)
[Mϩ ϩ 1], 239 (22), 212 (93), 84 (100). C11H7F3N2O2 (256.18):
calcd. C 51.57, H 2.75; found C 51.48, H 3.01.
were located and refined isotropically, whereas the remainder of the
atoms were optimized anisotropically. CCDC-179870 contains the
supplementary crystallographic data for this work. These data can
be obtained free of charge at www.ccdc.cam.ac.uk/conts/retriev-
ing.html [or from the Cambridge Crystallographic Data Centre, 12,
Union Road, Cambridge CB2 1EZ, UK; Fax: (internat.) ϩ44-1223/
336-033; E-mail: deposit@ccdc.cam.ac.uk].
The acid 18 (2.6 g, 10 mmol) was converted into the methyl ester
using ethereal diazomethane; white waxy mass; m.p. 29Ϫ31 °C; b.p.
1
76Ϫ78 g/0.1 Torr; yield: 2.5 g (93%). H NMR: δ ϭ 8.09 (dd, J ϭ
1-Phenyl-5-trifluoromethyl-4-pyrazolecarboxylic Acid (16): Diiso-
propylamine (2.8 mL, 2.0 g, 20 mmol), N,N,NЈ,NЈЈ,NЈЈ-pentame-
thyldiethylenetriamine (4.2 mL, 3.5 g, 20 mmol) and 1-phenyl-5-
(trifluoromethyl)pyrazole (5; 4.2 g, 20 mmol) were added consecut-
ively to a solution of butyllithium (20 mmol) in tetrahydrofuran (25
mL) and hexanes (10 mL) kept in a dry ice bath. After 5 min at
Ϫ75 °C, the mixture was poured onto an excess of freshly crushed
carbon dioxide, before being worked up as described above (see
acid 9). The product was purified by recrystallization; colorless
cubes; m.p. 132Ϫ134 °C (from chloroform and hexanes; ref.:[46]
7.8, 1.8 Hz, 1 H), 7.71 (td, J ϭ 7.8, 1.5 Hz, 1 H), 7.67 (td, J ϭ 7.8,
1.8 Hz, 1 H), 7.48 (d, J ϭ 7.8 Hz, 1 H), 6.81 (d, J ϭ 1.8 Hz, 1 H),
3.68 (s, 3 H) ppm. 19F NMR: δ ϭ Ϫ59.3 (s) ppm. MS (c.i.): m/z
(%) ϭ 271 (24) [Mϩ ϩ 1], 270 (69) [Mϩ], 240 (27), 239 (100), 212
(20). C12H9F3N2O2 (270.21): calcd. C 53.34, H 3.36; found C 53.61,
H 3.13.
4-Bromo-1-phenyl-5-trifluoromethyl-3-pyrazolecarboxylic Acid (19):
Diisopropylamine (1.4 mL, 1.0 g, 10 mmol), N,N,NЈ,NЈЈ,NЈЈ-penta-
methyldiethylenetriamine (2.1 mL, 1.7 g, 10 mmol) and 4-bromo-1-
phenyl-5-(trifluoromethyl)pyrazole (7; 3.0 g, 10 mmol) were added
consecutively to a solution of butyllithium (10 mmol) in tetrahy-
drofuran (20 mL) and hexanes (5 mL) kept in a dry ice bath. After
1
m.p. 129Ϫ131 °C); yield: 3.2 g (62%). H NMR: δ ϭ 8.22 (s, 1 H),
7.5 (m, 3 H), 7.4 (m, 2 H) ppm. 19F NMR: δ ϭ Ϫ55.9 ppm. MS
(c.i.): m/z (%) ϭ 257 (73) [Mϩ ϩ 1], 256 (100) [Mϩ], 239 (33).
2918
Eur. J. Org. Chem. 2002, 2913Ϫ2920