FULL PAPERS
Palladium-Catalysed CÀH Bond Electrophilic Fluorination
+
position occurs and even a recrystallisation was not efficient.
2.98, N 20.05; HR-MS (+p ESI): m/z=208.051 [M+H ],
1
H NMR (300 MHz, CDCl ): d=7.76 (s, 1H), 7.63 (s, 1H),
calcd. for C H FN O : 208.050.
3
9
6
3
2
19
7
.41–7.32 (m, 2H), 7.21–7.15 (m, 1H); F NMR (282 MHz,
3,5-Difluoro-4-(1H-pyrazol-1-yl)-nitrobenzene (17b): The
reaction of 4-(1H-pyrazol-1-yl)-nitrobenzene (94 mg,
0.5 mmol) and NFSI (788 mg, 2.5 mmol), affords 17b after
13
CDCl ): d=À118.4; C NMR (75 MHz, CDCl ): d=160.3
3
3
(
d, J=256.1 Hz), 142.2, 133.4, 132.2, 131.1 (d, J=9.0 Hz),
1
2
27.6 (d, J=6.8 Hz), 126.0 (d, J=3.7 Hz), 115.5 (d, J=
0.3 Hz), 95.0; HR-MS (+p ESI): m/z=276.934 [M+H ],
40 h; yield: 49.5 mg (44%); white solid; (ethyl acetate-hep-
+
1
tane=3:7); H NMR (300 MHz, CDCl ): d=8.04–7.97 (m,
3
calcd. for C H BrClFN : 276.930.
2H), 7.88 (d, J=1.73 Hz, 1H), 7.79–7.77 (m, 1H), 6.58 (dd,
9
5
2
1
9
3
-Fluoro-2-(4-methyl-1H-pyrazol-1-yl)-benzonitrile (10a):
The reaction of 2-(4-methyl-1H-pyrazol-1-yl)-benzonitrile
91.6 mg, 0.5 mmol) and NFSI (236.5 mg, 0.75 mmol), af-
J=2.57, 1.88 Hz, 1H); F NMR (282 MHz, CDCl ): d=
3
1
3
À114.1; C NMR (75 MHz, CDCl ): d=157.9 (dd, J=259.1,
3
(
3.94 Hz), 146.6 (m), 142.8, 132.2 (t, J=2.7 Hz), 124.3 (t, J=
14.0 Hz), 109.1 (m), 108.2; elemental analysis: calcd. (%) for
C H F N O : C 48.01, H 2.24, N 18.66; found: C 47.98, H
fords 10a; yield: 26.3 mg (26%); yellow oil; (ethyl acetate-
1
heptane=3:7); H NMR (300 MHz, CDCl ): d=7.67 (s,
3
9
6
2
3
2
+
1
H), 7.61–7.57 (m, 2H), 7.50-.38 (m, 2H), 2.18 (s, 3H);
2.66, N 18.03; HR-MS (+p ESI): m/z=226.041 [M+H ],
19
13
F NMR (470 MHz, CDCl ): d=À120.6;
C NMR
calcd. for C H F N O : 226.030.
3
9
6
2
3
2
(75 MHz, CDCl ): d=157.3 (d, J=253.6 Hz), 143.3, 131.2 (d,
1,3-Difluoro-2-(3-methyl-1H-pyrazol-1-yl)-benzene (19b):
The reaction of 3-methyl-1-phenyl-1H-pyrazole (79 mg,
0.5 mmol) and NFSI (788 mg, 2.5 mmol), affords 19b; yield:
3
J=15.3 Hz), 130.3 (d, J=4.0 Hz), 130.0 (d, J=4.8 Hz), 129.0
d, J=8.5 Hz), 121.7 (d, J=20.8 Hz), 119.0, 115.8 (d, J=
.0 Hz), 111.1 (d, J=2.0 Hz), 9.0; elemental analysis: calcd.
%) for C H FN : C 65.66, H 4.01, N 20.88, found: C 65.13,
(
4
34.7 mg (36%); yellow oil; (ethyl acetate-heptane=3:7);
1
(
H NMR (300 MHz, CDCl ): d=7.47 (m, 1H), 7.27–7.19 (m,
11
8
3
3
+
H 4.36, N 19.16; HR-MS (+p ESI): m/z=202.077 [M+H ],
1H), 7.00–6.92 (m, 2H), 6.20 (d, J=2.36 Hz, 1H), 2.31 (s,
1
9
13
calcd. for C H FN : 202.070.
3H); F NMR (282 MHz, CDCl ): d=À120.0; C NMR
11
8
3
3
1
-[2,6-(Difluoro)phenyl]-1H-pyrazole (15b): The reaction
of 1-phenyl-1H-pyrazole (66 mL, 0.5 mmol) and NFSI
788.4 mg, 2.5 mmol), affords 15b; yield: 79 mg (88%):
(75 MHz, CDCl ): d=159.3 (d, J=254.0 Hz), 159.2 (d, J=
3
254.0 Hz), 151.1, 133.0, 129.4 (t, J=9.8 Hz), 119.0 (t, J=
14.6 Hz), 112.5 (AA’X, N=12.0 Hz), 107.1, 13.8; elemental
analysis: calcd. (%) for C H F N : C 61.85, H 4.15, N 14.43;
(
1
yellow oil; (ethyl acetate-heptane=3:7);
H NMR
1
0
8
2
2
(
(
2
300 MHz, CDCl ): d=7.80 (d, J=1.73 Hz, 1H), 7.67–7.65
found: C 62.10, H 4.85, N 14.75; HR-MS (+p ESI): m/z=
3
+
m, 1H), 7.38–7.29 (m, 1H), 7.09–7.01 (m, 2H), 6.48 (dd, J=
195.072 [M+H ], calcd. for C H F N : 195.070.
1
0
8
2
2
1
9
.32, 2.03 Hz, 1H); F NMR (282 MHz, CDCl ): d=À120.2;
1,3-Difluoro-2-(4-chloro-1H-pyrazol-1-yl)-benzene (20b):
The reaction of 4-chloro-1-phenyl-1H-pyrazole (89 mg,
0.5 mmol) and NFSI (788 mg, 2.5 mmol), affords 20b; yield:
3
1
3
C NMR (75 MHz, CDCl ): d=159.2 (d, J=254.3 Hz),
3
1
1
59.1 (d, J=254.3 Hz), 141.6, 132.3, 129.7 (t, J=9.8 Hz),
18.9 (t, J=14.9 Hz), 112.5 (AA’X, N=12.0 Hz), 107.0: ele-
36.8 mg (34%); white solid; (ethyl acetate-heptane=3:7);
1
mental analysis: calcd. (%) for C H F N : C 60.00, H 3.36,
N 15.50; found: C 59.62, H 3.33, N 16.10; HR-MS (+p ESI):
m/z=181.056 [M+H ], calcd. for C H F N : 181.050.
H NMR (300 MHz, CDCl ): d=7.73 (s, 1H), 7.66 (m, 1H),
9
6
2
2
3
1
9
7.44–7.35 (m, 1H), 7.12–7.04 (m, 2H); F NMR (282 MHz,
+
13
CDCl ): d=À120.1; C NMR (125 MHz, CDCl ): d=158.5
9
6
2
2
3
3
3,5-Difluoro-4-(1H-pyrazol-1-yl)-trifluoromethylbenzene
(d, J=255.2 Hz), 158.5 (d, J=255.2 Hz), 140.4, 130.2 (t, J=
9.8 Hz), 130.1 (s), 118.3 (t, J=14.0 Hz), 112.7 (AA’X, N=
11.9 Hz), 112.1; elemental analysis: calcd. (%) for
C H ClF N : C 50.37, H 2.35, Cl 16.52, F 17.71, N 13.05;
(16b): The reaction of 4-(1H-pyrazol-1-yl)-trifluoromethyl-
benzene (212 mg, 1 mmol) and NFSI (1.26 g, 4 mmol), af-
fords 16b; yield: 44.1 mg (18%); white solid; (dichlorome-
9
5
2
2
thane-heptane=8:2+3% TEA, and then ethyl acetate-hep-
found: C 48.65, H 2.41, N 12.62; HR-MS (+p ESI): m/z=
1
+
tane=3:7+3% TEA); H NMR (300 MHz, CDCl ): d=7.85
215.017 [M+H ], calcd. for C H ClF N : 215.600.
3
9
5
2
2
(
6
d, J=1.71 Hz, 1H), 7.73–7.72 (m, 1H), 7.41–7.35 (m, 2H),
1,3-Difluoro-2-(4-bromo-1H-pyrazol-1-yl)-benzene (21b):
The reaction of 4-bromo-1-phenyl-1H-pyrazole (111 mg,
0.5 mmol) and NFSI (788 mg, 2.5 mmol), affords 21b; yield:
19
.54 (dd, J=2.44, 1.98 Hz,1 1H); F NMR (470 MHz,
3
CDCl ): d=À63.2, À116.1; C NMR (125 MHz, CDCl ):
3
3
d=158.0 (d, J=257.3 Hz), 158.0 (d, J=257.3 Hz), 142.4 (s),
49.9 mg (38%); yellow oil; (ethyl acetate-heptane=3:7);
1
1
3
32.2 (s), 131.8 (dt, J=35.1, 9.3 Hz), 123.6 (dt, J=272.5 Hz,
Hz), 121.9 (t, J=14.1 Hz), 110.6 (m), 107.8; elemental
H NMR (300 MHz, CDCl ): d=7.76 (s, 1H), 7.69 (m, 1H),
3
1
9
7.44–7.34 (m, 1H), 7.12–7.04 (m, 2H); F NMR (282 MHz,
1
3
analysis: calcd. (%) for C H F N : C 48.40, H 2.03, N 11.29;
found: C 49.20, H 2.57, N 10.94; HR-MS (+p ESI): m/z=
2
CDCl ): d=À120.0; C NMR (75 MHz, CDCl ): d=159.1
10
5
5
2
3
3
(d, J=255.2 Hz), 159.1 (d, J=255.2 Hz), 142.4, 132.3, 130.4
(t, J=9.7 Hz), 118. 5 (t, J=16.5 Hz), 112.7 (AA’X, N=
11,9 Hz), 95.3; elemental analysis: calcd. (%) for
C H BrF N : C 41.73, H 1.95, N 10.81; found: C 41.78, H
+
49.044 [M+H ], calcd. for C H F N : 249.040.
10 5 5 2
3
-Fluoro-4-(1H-pyrazol-1-yl)-nitrobenzene (17a): The re-
action of 4-(1H-pyrazol-1-yl)-nitrobenzene (94 mg,
.5 mmol) and NFSI (473 mg, 1.5 mmol), affords 17a after
7 h; yield: 26.8 mg (24%); white solid; (ethyl acetate-hep-
9
6
2
2
+
0
1
2.21, N 11.06; HR-MS (+p ESI): m/z=258.967 [M+H ],
calcd. for C H BrF N : 258.960.
9
6
2
2
1
tane=3:7); H NMR (300 MHz, CDCl ): d=8.30–8.27 (m,
1,3-Difluoro-2-(4-nitro-1H-pyrazol-1-yl)-benzene
(22b):
3
1
H), 8.20–8.13 (m, 3H), 7.82 (d, J=1.63 Hz, 1H), 6.57 (dd,
The reaction of 4-nitro-1-phenyl-1H-pyrazole (64.1 mg,
0.34 mmol) and NFSI (428.9 mg, 1.36 mmol), affords 22b
19
J=2.65, 1.79 Hz, 1H); F NMR (282 MHz, CDCl ): d=
3
13
À120.6; C NMR (75 MHz, CDCl ): d=153.5 (d, J=
after 40 h; yield: 44.2 mg (57%); yellow oil; (ethyl acetate-
3
1
2
1
52.4 Hz), 145.5 (b), 142.5, 133.5 (d, J=8.8 Hz), 131.4 (d, J=
4.3 Hz), 123.8 (d, J=1.2 Hz), 120.7 (d, J=3.4 Hz), 113.6 (d,
heptane=3:7); H NMR (300 MHz, CDCl ): d=8.41 (b,
3
1H), 8.34 (s, 1H), 7.55–7.45 (m, 1H), 7.19–7.15 (m, 2H);
1
9
13
J=26.2 Hz), 109.4; elemental analysis: calcd. (%) for
C H FN O : C 52.18, H 2.92, N 20.28; found: C 52.19, H
F NMR (282 MHz, CDCl ): d=À119.6;
C NMR
3
(75 MHz, CDCl ): d=159.0 (d, J=255.2 Hz), 158.9 (d, J=
9
6
3
2
3
Adv. Synth. Catal. 2015, 357, 2913 – 2923
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2921