2.5 mmol), and CsF (0.15 g, 1.0 mmol) in dioxane (5 mL) was
degassed with Ar for 30 min before the addition of Pd(dba)2
(14 mg, 25 mmol), and PPh3 (26 mg, 0.10 mmol). The resulting
mixture was heated at 105 ◦C for 12 h, before cooling and dilution
with Et2O (30 mL), washing with H2O and extraction with
CH2Cl2 (3 ¥ 20 mL). After drying over Na2SO4, the solvent was
evaporated under reduced pressure, and the coupled product 4b
was isolated by purification by flash chromatography on silica
2.7 and JF = 5.4). 13C NMR (CDCl3, 75 MHz) 81.0 (d, JF = 28),
81.1, 115.5 (d, JF = 26), 118.0, 128.1 (d, JF = 8), 137.3 (d, JF
=
3), 143.2, 143.3, 161.7 (d, JF = 248). 19F NMR (CDCl3, 282 MHz)
-93.4. HRMS (ESI): calcd for C9H6FI2N2 [M + H]+ 414.8605,
found 414.8627.
5-Iodo-1-(2-iodo-4-methoxyphenyl)-1H-pyrazole
(3g). This
was prepared from 1g following the general procedure and was
obtained as a white solid (60% yield; mp = 98 ◦C). IR (ATR):
3005, 2925, 2852, 1592, 1567, 1496, 1396, 1384, 1291, 1231, 1221,
◦
gel as a white solid (73% yield; mp = 140 C). IR (ATR): 2891,
1
2805, 1624, 1524, 1361, 1068, 924, 803 cm-1. H NMR (CDCl3,
1
1027, 1017, 957, 917 cm-1. H NMR (CDCl3, 300 MHz) 3.86 (s,
300 MHz) 2.96 (s, 6H), 6.48 (d, 1H, J = 1.4), 6.65 (d, 2H, J = 8.8),
3H), 6.61 (d, 1H, J = 1.9), 6.98 (dd, 1H, J = 2.8 and 8.7), 7.25 (d,
1H, J = 8.7), 7.45 (d, 1H, J = 2.8), 7.71 (d, 1H, J = 1.9). 13C NMR
(CDCl3, 75 MHz) 56.0, 84.4, 98.8, 114.6, 116.2, 124.4, 130.0,
136.1, 142.8, 160.6. HRMS (ESI): calcd for C10H9I2N2O [M + H]+
426.8804, found 426.8811.
7.15 (d, 2H, J = 8.8), 7.25–7.29 (m, 5H), 7.68 (d, 1H, J = 1.4). 13
C
NMR (CDCl3, 75 MHz) 40.8 (2C), 107.1, 112.4 (2C), 126.3 (2C),
128.0, 128.5 (2C), 128.8 (2C), 131.0, 132.4, 139.7, 142.8, 149.6.
HRMS (ESI): calcd for C17H18N3 [M + H]+ 264.1501, found
264.1499.
5-Iodo-1-(3-methoxyphenyl)-1H-pyrazole (2h). This was pre-
pared from 1h following the general procedure and was obtained
as a yellow liquid (12% yield; 70% using 1.0 mmol of 2,2,6,6-
tetramethylpiperidine, 1.0 mmol of BuLi and 0.33 mmol of
ZnCl2·TMEDA). IR (ATR): 2961, 2835, 1606, 1593, 1497, 1384,
1-(4-Cyano-2-iodophenyl)-5-iodo-1H-pyrazole (3d). This was
prepared from 1d following the general procedure and was
obtained as a white solid (65% yield; mp = 112 ◦C). IR (ATR):
2924, 2852, 2230, 1608, 1525, 1493, 1389, 1026, 957, 837 cm-1. 1H
NMR (CDCl3, 300 MHz) 6.67 (d, 1H, J = 1.7), 7.45 (d, 1H, J =
8.1), 7.73 (d, 1H, J = 1.8), 7.79 (dd, 1H, J = 1.8 and 8.1), 8.25 (d,
1H, J = 1.7). 13C NMR (CDCl3, 75 MHz) 82.8, 98.8, 115.2, 116.2,
117.1, 130.3, 132.6, 142.9, 143.5, 146.7. HRMS (ESI): calcd for
C10H6I2N3 [M + H]+ 421.8651, found 421.8655.
1
1219, 1036, 971, 847 cm-1. H NMR (CDCl3, 300 MHz) 3.85 (s,
3H), 6.62 (d, 1H, J = 1.9), 6.98 (ddd, 1H, J = 0.9, 2.4 and 8.2), 7.06
(dd, 1H, J = 2.0 and 2.4), 7.11 (ddd, 1H, J = 0.9, 2.0 and 7.9), 7.38
(dd, 1H, J = 7.9 and 8.2), 7.68 (d, 1H, J = 1.9). 13C NMR (CDCl3,
75 MHz) 55.7, 80.8, 111.8, 115.0, 117.6, 118.6, 129.6, 141.2, 142.7,
159.9. HRMS (ESI): calcd for C10H10IN2O [M + H]+ 300.9838,
found 300.9836.
5-Iodo-1-[2-iodo-4-(trifluoromethyl)phenyl]-1H-pyrazole (3e).
This was prepared from 1e following the general procedure and
was obtained as a yellow liquid (84% yield). IR (ATR): 1604,
1501, 1397, 1383, 1317, 1169, 1126, 1070, 957, 709 cm-1. 1H
NMR (CDCl3, 300 MHz) 6.65 (d, 1H, J = 1.8), 7.46 (d, 1H, J =
8.2), 7.72 (d, 1H, J = 1.7), 7.76 (dd, 1H, J = 1.7 and 8.2), 8.21
(d, 1H, J = 1.8). 13C NMR (CDCl3, 75 MHz) 83.0, 98.6, 116.7,
122.3 (q, JF = 273), 125.9 (q, JF = 4), 130.1, 132.9 (q, JF = 33),
136.6 (q, JF = 4), 143.1, 146.0. 19F (CDCl3, 282 MHz) -62.6 (3F).
HRMS (ESI): calcd for C10H6F3I2N2 [M + H]+ 464.8573, found
464.8572.
5-Iodo-1-(2-iodo-3-methoxyphenyl)-1H-pyrazole
(3h). This
was prepared from 1h following the general procedure and was
obtained as a yellow solid (61% yield; 7% using 1.0 mmol of
2,2,6,6-tetramethylpiperidine, 1.0 mmol of BuLi and 0.33 mmol
◦
of ZnCl2·TMEDA; mp = 132 C). IR (ATR): 3005, 2934, 2836,
1733, 1575, 1472, 1400, 1218, 1130, 971 cm-1. 1H NMR (CDCl3,
300 MHz) 3.96 (s, 3H), 6.63 (d, 1H, J = 1.9), 6.93 (dd, 1H, J =
1.2 and 8.4), 6.99 (dd, 1H, J = 1.2 and 7.8), 7.44 (dd, 1H, J =
7.8 and 8.4), 7.70 (dd, 1H, J = 1.9). 13C NMR (CDCl3, 75 MHz)
57.0, 83.4, 91.3, 111.9, 116.5, 122.1, 129.7, 139.8, 142.7, 159.4.
HRMS (ESI): calcd for C10H9I2N2O [M + H]+ 426.8804, found
426.8810.
1-(4-Fluoro-2-iodophenyl)-5-iodo-1H-pyrazole (3f). This was
prepared from 1f following the general procedure and was
obtained as a yellow solid (31% yield; 57% using 3.0 mmol of
2,2,6,6-tetramethylpiperidine, 3.0 mmol of BuLi and 1.0 mmol of
ZnCl2·TMEDA; mp = 78 ◦C). IR (ATR): 3097, 1589, 1492, 1393,
1,1¢[1,4-(2-Iodophenylene)bis-(1H-5-iodopyrazole)] (5i). This
was prepared from 1i following the general procedure and
was obtained as a white solid (61% yield using 3.0 mmol of
2,2,6,6-tetramethylpiperidine, 3.0 mmol of BuLi and 1.0 mmol
1
1202, 1023, 958, 862 cm-1. H NMR (CDCl3, 300 MHz) 6.63 (d,
1H, J = 1.9), 7.19 (ddd, 1H, J = 2.7, 8.7 and JF = 7.7), 7.32 (dd,
1H, J = 8.7 and JF = 5.3), 7.67 (dd, 1H, J = 2.7 and JF = 7.7), 7.70
◦
(d, 1H, J = 1.9). 13C NMR (CDCl3, 75 MHz) 83.7, 98.6 (d, JF
=
of ZnCl2·TMEDA; mp = 174 C). IR (ATR): 3129, 2924, 2854,
1
1724, 1592, 1501, 1393, 1372, 954, 917 cm-1. H NMR (CDCl3,
9), 116.0 (d, JF = 23), 116.5, 126.5 (d, JF = 25), 130.6 (d, JF = 9),
139.4, (d, JF = 4), 143.0, 162.2 (d, JF = 255). 19F NMR (CDCl3,
282 MHz) -108.9. HRMS (ESI): calcd for C9H6FI2N2 [M + H]+
414.8605, found 414.8605.
300 MHz) 6.64 (d, 1H, J = 1.8), 6.65 (d, 1H, J = 1.8), 7.44 (d,
1H, J = 8.4), 7.70 (dd, 1H, J = 2.3 and 8.4), 7.71 (d, 1H, J = 1.8),
7.72 (d, 1H, J = 1.8), 8.17 (d, 1H, J = 2.3). 13C NMR (CDCl3,
75 MHz) 80.6, 83.6, 98.1, 116.7, 118.7, 126.3, 129.6, 136.7, 141.4,
142.8, 143.1, 143.6. HRMS (ESI): calcd for C12H8I3N4 [M + H]+
588.7883, found 588.7897.
1-(4-Fluoro-3-iodophenyl)-5-iodo-1H-pyrazole (3¢f). This was
prepared from 1f following the general procedure and was
obtained as a brown solid (22% yield using 3.0 mmol of 2,2,6,6-
tetramethylpiperidine, 3.0 mmol of BuLi and 1.0 mmol of
ZnCl2·TMEDA; mp = 61 ◦C). IR (ATR): 3097, 2924, 1591, 1491,
1,1¢[1,2-(3-Iodophenylene)bis(1H-5-iodopyrazole)] (5j). This
was prepared from 1j following the general procedure and
was obtained as a white solid (37% yield using 3.0 mmol of
2,2,6,6-tetramethylpiperidine, 3.0 mmol of BuLi and 1.0 mmol of
ZnCl2·TMEDA; mp = 214 ◦C). IR (ATR): 2924, 2853, 1731, 1485,
1
1389, 1038, 965, 819 cm-1. H NMR (CDCl3, 300 MHz) 6.62 (d,
1H, J = 1.8), 7.16 (dd, 1H, J = 8.9 and JF = 7.3), 7.51 (ddd, 1H,
J = 2.7, 8.9 and JF = 4.5), 7.67 (d, 1H, J = 1.8), 7.93 (dd, 1H, J =
4680 | Org. Biomol. Chem., 2011, 9, 4671–4684
This journal is
The Royal Society of Chemistry 2011
©