T. Hanamoto et al. / Tetrahedron 63 (2007) 5062–5070
5067
(
CDCl , 300 MHz) d 7.57 (1H, d, J¼4.6 Hz), 8.04 (2H, dt,
3139, 2915, 1627, 1601, 1538, 1471, 1435, 1296, 1248,
1209, 1176, 1064, 1035, 941, 837, 768, 696 cm ; H
NMR (CDCl , 300 MHz) d 3.85 (3H, s), 6.89–6.94 (1H,
3
3
ꢀ
1
1
J¼9.0, 2.2 Hz), 8.30 (2H, dt, J¼9.0, 2.2 Hz), 10.03 (1H, br
1
3
s); C NMR (CDCl , 150 MHz) d 124.1, 126.4 (d,
3
1
9
J¼3.7 Hz), 147.2, 148.2 (d, J¼251.3 Hz);
F NMR
m), 7.32–7.39 (3H, m), 7.50 (1H, d, J¼4.6 Hz), 10.33 (1H,
1
3
(
m/z 207 (100, M ), 206 (13), 177 (40), 149 (32), 134 (56),
CDCl , 283 MHz) d ꢀ175.4 (1F, d, J¼4.6 Hz); GC–MS
br s); C NMR (CDCl , 75 MHz) d 55.1, 111.1, 114.0,
3
3
+
118.3, 121.1 (d, J¼20.6 Hz), 129.9, 130.2, 133.2, 147.1 (d,
1
9
1
5
07 (11), 75 (50), 50 (17). Anal. Calcd for C H FN O : C,
9
J¼247.9 Hz), 159.8;
F NMR (CDCl , 283 MHz)
3
6
3
2
+
2.18; H, 2.92; N, 20.28. Found: C, 52.31; H, 2.99; N, 20.10.
d ꢀ177.2 (1F, d, J¼4.6 Hz); GC–MS m/z 192 (100, M ),
91 (33), 163 (19), 162 (22), 149 (24), 120 (6), 101 (7), 77
(13), 63 (4). Anal. Calcd for C H FN O: C, 62.49; H,
1
3
yield 99%; mp 82.5–83.3 C; IR (KBr) 3166, 3140, 2890,
.1.6. 4-Fluoro-5-phenyl-1H-pyrazole (6f). White solid;
ꢁ
1
0
9
2
4.72; N, 14.58. Found: C, 62.57; H, 4.82; N, 14.47.
ꢀ
1
1
600, 1532, 1447, 1363, 1187, 1097, 940, 759, 691 cm
H NMR (CDCl , 300 MHz) d 7.33–7.47 (3H, m), 7.50
;
1
0
To a solution containing 91.0 mg
(0.243 mmol) of pyrazole 3 and 4 -iodoacetophenone
3.1.11. Preparation of 5-(4 -acetylbenzoyl)-4-fluoro-1H-
pyrazole (7a).
3
1
9
(
s);
1H, d, J¼4.4 Hz), 7.76 (2H, dt, J¼7.5 Hz), 10.35 (1H, br
1
3
0
(65.2 mg, 0.265 mmol) in DMSO (1 mL) was added a cata-
C NMR (CDCl , 75 MHz) d 121.1, 125.9 (d,
3
1
9
J¼3.7 Hz), 128.3, 128.9, 129.1, 147.2 (d, J¼247.9 Hz);
F
NMR (CDCl , 283 MHz) d ꢀ178.2 (1F, s); GC–MS m/z
lytic amount of Pd(PPh ) (14.1 mg, 5 mol %). After argon
3 4
3
+
1
62 (51, M ), 161 (100), 133 (11), 108 (47), 107 (68), 106
18), 104 (15), 77 (67), 76 (35), 51 (22). Anal. Calcd for
in the flask was replaced with carbon monoxide (balloon),
ꢁ
(
C H FN : C, 66.66; H, 4.35; N, 17.27. Found: C, 66.38; H,
4
the whole mixture was heated to 80 C. After being stirred
for 24 h at this temperature, the resulting mixture was cooled
to room temperature. After removal of remaining carbon
monoxide, the reaction mixture was quenched with hexane/
ethyl acetate¼3/1 solution and brine, and then extracted
with ethyl acetate. The combined organic layer was dried
over Na SO , and concentrated under reduced pressure. To
9
7
2
.44; N, 17.04.
0
azole (6g). White solid; yield 83%; mp 96.9–99.0 C; IR
3
.1.7. 4-Fluoro-5-(2 -methoxycarbonylphenyl)-1H-pyr-
ꢁ
(
1
3
KBr) 3316, 3170, 2953, 1728, 1587, 1435, 1296, 1263,
2
4
ꢀ1
1
129, 1092, 767, 720, 669 cm
00 MHz) d 3.81 (3H, s), 7.41–7.63 (4H, m), 7.87 (1H, d,
;
H NMR (CDCl3,
the residue was added hexane/ethyl acetate¼3/1 solution
(ca. 5 mL) and saturated aqueous KF solution (ca. 5 mL),
and the mixture stirred vigorously for a few minutes. The or-
ganic layer was separated, dried over Na SO , and concen-
1
3
J¼7.7 Hz), 10.26 (1H, br s); C NMR (CDCl , 75 MHz)
3
d 52.3, 119.1 (d, J¼21.2 Hz), 128.4, 128.8 (d, J¼3.7 Hz),
2
4
1
30.1, 130.25, 130.28, 130.4, 131.7, 147.1 (d,
F NMR (CDCl3, 283 MHz)
trated under reduced pressure. The residue was purified by
Florisil column chromatography (hexane/ethyl acetate/
triethylamine¼200/20/1, then 200/200/1) to give the desired
compound (7a) as a white solid (48.0 mg, 85%): mp 175.9–
1
9
J¼146.0 Hz), 168.5;
+
d ꢀ177.5 (1F, d, J¼5.8 Hz); GC–MS m/z 220 (11, M ),
1
(
6
89 (19), 188 (100), 133 (14), 132 (97), 131 (29), 106
16), 75 (6), 50 (7). Anal. Calcd for C H FN O : C,
ꢁ
176.6 C; IR (KBr) 3269, 3148, 3117, 1657, 1574, 1504,
1470, 1278, 1143, 915 cm ; H NMR (CDCl , 300 MHz)
1
1
9
2 2
ꢀ
1 1
0.00; H, 4.12; N, 12.72. Found: C, 60.21; H, 4.42; N, 12.22.
3
d 2.67 (3H, s), 7.59 (1H, d, J¼5.3 Hz), 8.04 (4H, br s),
0
White solid; yield 89%; mp 70.6–71.5 C; IR (KBr) 3161,
19
3
.1.8. 5-(2 -Chlorophenyl)-4-fluoro-1H-pyrazole (6h).
ꢁ
134, 2945, 1585, 1529, 1452, 1427, 1190, 1078, 937, 758,
10.66 (1H, br s); F NMR (CDCl , 283 MHz) d ꢀ176.4
3
+
(1F, s); GC–MS m/z 232 (0.4, M ), 216 (100), 133 (46),
3
7
113 (65), 107 (19), 104 (31), 90 (24), 76 (62), 57 (24), 50
(32). Anal. Calcd for C H FN O : C, 62.07; H, 3.91; N,
12.06. Found: C, 61.70; H, 4.10; N, 11.97.
ꢀ
1 1
41, 675 cm ; H NMR (CDCl , 300 MHz) d 7.31–7.59
3
12
9
2 2
1
3
(
5H, m), 11.09 (1H, br s); C NMR (CDCl , 75 MHz)
3
d 120.3, 126.8, 127.8 (d, J¼3.7 Hz), 129.99, 130.18,
1
9
0
azole (7b). White solid; yield 91%; mp 149.6–150.3 C; IR
1
31.05 (d, J¼2.5 Hz), 132.8, 147.1 (d, J¼247.9 Hz);
F
3.1.12. 5-(4 -Ethoxycarbonylbenzoyl)-4-fluoro-1H-pyr-
ꢁ
(KBr) 3188, 1717, 1634, 1567, 1448, 1280, 1201, 1023,
NMR (CDCl , 283 MHz) d ꢀ175.3 (1F, s); GC–MS m/z
3
+
1
(
96 (100, M ), 195 (12), 134 (25), 133 (12), 107 (16), 102
9), 75 (12). Anal. Calcd for C H ClFN : C, 54.98; H,
ꢀ
1
1
915, 831, 746, 722 cm ; H NMR (CDCl , 300 MHz)
3
9
6
2
3
.08; N, 14.25. Found: C, 55.31; H, 3.20; N, 14.07.
d 1.43 (3H, t, J¼7.2 Hz), 4.43 (2H, q, J¼7.2 Hz), 7.58 (1H,
19
d, J¼4.6 Hz), 8.00–8.10 (2H, m), 8.15–8.20 (2H, m), 10.61
0
6i). White solid; yield 94%; mp 90.2–91.3 C; IR (KBr)
0
3
(
.1.9. 4-Fluoro-5-(2 ,4 -dimethylphenyl)-1H-pyrazole
(1H, br s); F NMR (CDCl , 283 MHz) d ꢀ168.3 (1F, s);
3
ꢁ
157, 3087, 2927, 1608, 1527, 1445, 1357, 1098, 941, 817,
+
GC–MS m/z 262 (3.3, M ), 261 (30), 216 (100), 188 (48),
3
6
2
1
148 (46), 133 (40), 113 (74), 112 (90), 104 (56), 76 (69),
75 (79), 50 (43). Anal. Calcd for C H FN O : C, 59.54;
H, 4.23; N, 10.68. Found: C, 59.67; H, 4.52; N, 10.27.
ꢀ
1
1
75 cm ; H NMR (CDCl , 300 MHz) d 2.32 (3H, s),
3
13 11
2 3
.36 (3H, s), 7.05–7.26 (3H, m), 7.45 (1H, d, J¼4.6 Hz),
1
3
0.44 (1H, br s); C NMR (CDCl , 75 MHz) d 19.8 (d,
3
0
azole (7c). White solid; yield 67%; mp 154.8–156.3 C; IR
J¼3.7 Hz), 21.1, 121.8, 124.9, 129.52, 129.57, 131.3,
3.1.13. 4-Fluoro-5-(4 -trifluoromethylbenzoyl)-1H-pyr-
ꢁ
(KBr) 3155, 1651, 1574, 1446, 1337, 1066, 1017, 956, 914,
1
9
1
2
1
7
1
36.8, 138.8, 146.8 (d, J¼244.8 Hz); F NMR (CDCl ,
3
+
83 MHz) d ꢀ177.2 (1F, s); GC–MS m/z 190 (100, M ),
ꢀ
1
1
89 (17), 175 (13), 162 (30), 148 (21), 146 (11), 115 (11),
7 (10). Anal. Calcd for C H FN : C, 69.46; H, 5.83; N,
4.73. Found: C, 69.43; H, 5.88; N, 14.74.
860, 820, 783, 699, 666 cm
;
H NMR (CDCl3,
300 MHz) d 7.70 (1H, d, J¼4.6 Hz), 7.78 (2H, d, J¼
1
1
11
2
1
9
8.3 Hz), 8.12 (2H, d, J¼8.3 Hz), NH proton is missing;
F
NMR (CDCl , 283 MHz) d ꢀ64.4 (3F, s), ꢀ165.9 (1F, s);
3
0
White solid; yield 74%; mp 53.2–55.0 C; IR (KBr) 3168,
+
3
.1.10. 4-Fluoro-5-(3 -methoxylphenyl)-1H-pyrazole (6j).
ꢁ
GC–MS m/z 258 (0.9, M ), 257 (26), 173 (35), 172 (57),
145 (84), 144 (100), 113 (69), 112 (65), 95 (30), 75 (26),