2768 J . Org. Chem., Vol. 61, No. 8, 1996
Ichikawa et al.
was purified by thin layer chromatography on silica gel
(hexane-ethyl acetate 5:1) to give 3a and 2a (82 mg, 97%,
3a /2a ) 97/3) as a pale yellow liquid. 3a : 1H NMR (500 MHz,
CDCl3) δ 0.81 (3H, t, J ) 7.6 Hz), 1.24 (2H, tq, J ) 7.6, 7.6
Hz), 1.42 (2H, tt, J ) 7.6, 7.6 Hz), 2.30 (2H, t, J ) 7.6 Hz),
3.59 (3H, d, J HF ) 0.6 Hz), 7.28-7.32 (2H, m), 7.42-7.50 (3H,
m). 13C NMR (126 MHz, CDCl3) δ 13.7, 21.4 (d, J CF ) 3 Hz),
22.2, 32.2, 36.8, 102.4 (d, J CF ) 21 Hz), 128.7, 128.9, 129.7,
129.9, 142.5, 161.8 (d, J CF ) 243 Hz). 19F NMR (471 MHz,
CDCl3) 26.5 (1F, s) ppm. IR (neat) 2950, 2925, 2875, 1495,
1385, 1220, 1075, 1005, 770, 705 cm-1. MS (70 eV) m/ z (rel
intensity) 232 (M+; 32), 189 (100), 169 (9). Anal. Calcd for
C14H17N2F: C, 72.39; H, 7.38; N, 12.06. Found: C, 72.71; H,
7.37; N, 11.90.
µL, 0.46 mmol) in DMF (3 mL). Purification by thin layer
chromatography on silica gel (hexane-ethyl acetate 5:1) gave
3i and 4-butyl-5-fluoro-1-isopropyl-3-phenylpyrazole 2i (97 mg,
89%, 3i/2i ) 64/36) as a colorless liquid. 1H NMR (500 MHz,
CDCl3, for 3/2 3i/2i mixture) δ 0.81 (1.8H, t, J ) 7.4 Hz), 0.89
(1.2H, t, J ) 7.6 Hz), 1.22 (1.2H, tq, J ) 7.4, 7.4 Hz), 1.33
(0.8H, tq, J ) 7.6, 7.6 Hz), 1.35 (3.6H, d, J ) 6.7 Hz), 1.41
(1.2H, tt, J ) 7.4, 7.4 Hz), 1.51 (2.4H, d, J ) 6.7 Hz), 1.53
(0.8H, tt, J ) 7.6, 7.6 Hz), 2.26 (1.2H, t, J ) 7.4 Hz), 2.52 (0.8H,
t, J ) 7.6 Hz), 4.23 (0.6H, septd, J ) 6.7 Hz, J HF ) 2.8 Hz),
4.51 (0.4H, sept, J ) 6.7 Hz), 7.25-7.32 (1.6H, m), 7.38 (0.6H,
t, J ) 7.6 Hz), 7.41-7.49 (2.0H, m), 7.61 (0.8H, dd, J ) 8.2,
1.1 Hz). 13C NMR (126 MHz, CDCl3) 3i: δ 13.7, 21.3 (d, J CF
) 3 Hz), 21.8, 22.5, 32.3, 49.9, 101.9 (d, J CF ) 21 Hz), 127.5,
128.7, 129.8, 130.2, 141.6, 162.0 (d, J CF ) 242 Hz); 2i: δ 13.8,
22.1 (d, J CF ) 3 Hz), 22.2, 22.5, 32.0, 50.1, 98.4 (d, J CF ) 12
Hz), 127.5, 128.4, 128.9, 134.6, 147.9 (d, J CF ) 9 Hz), 151.0 (d,
J CF ) 275 Hz). IR (neat) 3280, 2940, 1725, 1670, 1600, 1495,
1,4-Dibu tyl-3-flu or o-5-p h en ylp yr a zole (3b). Compound
3b was prepared by the method described for 3a using sodium
hydride (17 mg, 60.4% dispersion in mineral oil, 0.44 mmol),
4a (84 mg, 0.39 mmol), and butyl iodide (49 µL, 0.43 mmol) in
DMF (3 mL). Purification by thin layer chromatography on
silica gel (hexane-ethyl acetate 3:1) gave 3b and 2b (102 mg,
96%, 3b/2b ) 84/16) as a pale yellow liquid. 3b: 1H NMR (500
MHz, CDCl3) δ 0.80 (3H, t, J ) 7.4 Hz), 0.80 (3H, t, J ) 7.4
Hz), 1.17 (2H, tq, J ) 7.4, 7.4 Hz), 1.23 (2H, tq, J ) 7.4, 7.4
Hz), 1.41 (2H, tt, J ) 7.4, 7.4 Hz), 1.68 (2H, tt, J ) 7.4, 7.4
Hz), 2.28 (2H, t, J ) 7.4 Hz), 3.81 (2H, t, J ) 7.4 Hz), 7.26-
7.30 (2H, m), 7.41-7.49 (3H, m). 13C NMR (126 MHz, CDCl3)
δ 13.6, 13.7, 19.7, 21.3 (d, J CF ) 4 Hz), 22.2, 32.2, 32.3, 48.9,
102.2 (d, J CF ) 20 Hz), 128.7, 128.9, 129.8, 130.1, 142.5, 161.9
(d, J CF ) 243 Hz). 19F NMR (471 MHz, CDCl3) 26.6 (1F, s)
ppm. IR (neat) 2975, 2950, 2900, 1575, 1500, 1470, 1405, 1390,
1220, 1050, 960, 850, 760, 700 cm-1
. MS (70 eV) m/ z (rel
intensity) 3i: 260 (M+; 42), 245 (14), 217 (100), 175 (93), 155
(14), 128 (10); 2i: 260 (M+; 46), 245 (36), 217 (83), 175 (100),
155 (13), 128 (10). HRMS 3i: Calcd for C16H21N2F 260.1689
(M+); found 260.1685; 2i: Calcd for C16H21N2F 260.1689 (M+);
found 260.1648. Anal. Calcd for C16H21N2F: C, 73.81; H, 8.13;
N, 10.76. Found: C, 73.76; H, 7.87; N, 10.48.
4-Bu tyl-3-flu or o-1-p-n itr oph en yl-5-ph en ylpyr azole (3j).
Compound 3j was prepared by the method described for 3a
using sodium hydride (20 mg, 62.0% dispersion in mineral oil,
0.51 mmol), 4a (101 mg, 0.46 mmol), and p-fluoronitrobenzene
(54 µL, 0.51 mmol) in DMF (3 mL). Purification by thin layer
chromatography on silica gel (hexane-ethyl acetate 20:1) gave
3j and 4-butyl-5-fluoro-1-(p-nitrophenyl)-3-phenylpyrazole (2j)
1220, 770, 710 cm-1
.
MS (70 eV) m/ z 274 (M+), 231 (base
peak), 189, 175, 128, 77. Anal. Calcd for C17H23N2F: C, 74.42;
H, 8.45; N, 10.21. Found: C, 74.59; H, 8.63; N, 10.02.
1
(151 mg, 96%, 3j/2j ) 68/32) as a pale yellow liquid. 3j: H
1-Ben zyl-4-bu tyl-3-flu or o-5-p h en ylp yr a zole (3c). Com-
pound 3c was prepared by the method described for 3a using
sodium hydride (16 mg, 60.4% dispersion in mineral oil, 0.40
mmol), 4a (80 mg, 0.37 mmol), and benzyl bromide (64 mg,
0.41 mmol) in DMF (2 mL). Purification by thin layer
chromatography on silica gel (hexane-ethyl acetate 5:1) gave
3c and 2c (110 mg, 98%, 3c/2c ) 90/10) as a pale yellow liquid.
3c: 1H NMR (500 MHz, CDCl3) δ 0.81 (3H, t, J ) 7.4 Hz), 1.24
(2H, tq, J ) 7.4 , 7.4 Hz), 1.43 (2H, tt, J ) 7.4, 7.4 Hz), 2.30
(2H, t, J ) 7.4 Hz), 5.03 (2H, s), 7.01 (2H, d, J ) 7.5 Hz), 7.20-
7.27 (5H, m), 7.39-7.43 (3H, m). 13C NMR (68 MHz, CDCl3)
δ 13.6, 21.3 (d, J CF ) 4 Hz), 22.1, 32.1, 52.8, 103.0 (d, J CF ) 21
Hz), 127.0, 127.4, 128.4, 128.6, 128.9, 129.7, 129.8, 137.2,
142.9, 162.1 (d, J CF ) 244 Hz). 19F NMR (94 MHz, CDCl3)
27.6 (1F, s) ppm. IR (neat) 2950, 2850, 1605, 1555, 1490, 1215,
1155, 1070, 765, 700 cm-1. MS (70 eV) m/ z (rel intensity) 308
(M+; 32), 265 (73), 91 (100). Anal. Calcd for C20H21N2F: C,
77.89; H, 6.86; N, 9.08. Found: C, 77.93; H, 7.06; N, 8.89.
1-Allyl-4-bu tyl-3-flu or o-5-p h en ylp yr a zole (3d ). Com-
pound 3d was prepared by the method described for 3a using
sodium hydride (15 mg, 60.4% dispersion in mineral oil, 0.37
mmol), 4a (74 mg, 0.34 mmol), and allyl bromide (45 mg, 0.37
mmol) in DMF (2 mL). Purification by thin layer chromatog-
raphy on silica gel (hexane-ethyl acetate 3:1) gave 3d and
2d (86 mg, 98%, 3d /2d ) 88/12) as a pale yellow liquid. 3d :
1H NMR (500 MHz, CDCl3) δ 0.81 (3H, t, J ) 7.5 Hz), 1.24
(2H, tq, J ) 7.5, 7.5 Hz), 1.43 (2H, tt, J ) 7.5, 7.5 Hz), 2.30
NMR (500 MHz, CDCl3) δ 0.85 (3H, t, J ) 7.5 Hz), 1.29 (2H,
tq, J ) 7.5, 7.5 Hz), 1.50 (2H, tt, J ) 7.5, 7.5 Hz), 2.40 (2H, t,
J ) 7.5 Hz), 7.21-7.24 (2H, m), 7.29-7.33 (2H, m), 7.41-7.49
(3H, m), 8.07-8.11 (2H, m). 13C NMR (126 MHz, CDCl3) δ
13.7, 21.3 (d, J CF ) 3 Hz), 22.3, 31.9, 107.8 (d, J CF ) 21 Hz),
123.4, 124.4, 129.2, 129.6, 129.7, 142.2, 144.4, 145.3, 164.4 (d,
J CF ) 249 Hz). 19F NMR (471 MHz, CDCl3) 31.0 (1F, s) ppm.
IR (neat) 2925, 1595, 1495, 1335, 1110, 960, 855, 750, 700 cm-1
.
MS (70 eV) m/ z (rel intensity) 339 (M+; 25), 296 (100), 250
(21), 77 (8). Anal. Calcd for C19H18N3O2F: C, 67.25; H, 5.35;
N, 12.38. Found: C, 67.53; H, 5.58; N, 12.05. 2j: 1H NMR
(500 MHz, CDCl3) δ 0.92 (3H, t, J ) 7.5 Hz), 1.38 (2H, tq, J )
7.5, 7.5 Hz), 1.59 (2H, tt, J ) 7.5, 7.5 Hz), 2.63 (2H, t, J ) 7.5
Hz), 7.40-7.50 (3H, m), 7.68-7.72 (2H, m), 7.95-8.00 (2H,
m), 8.32-8.36 (2H, m). 13C NMR (126 MHz, CDCl3) δ 13.7,
21.9 (d, J CF ) 3 Hz), 22.4, 31.5, 102.2 (d, J CF ) 13 Hz), 119.9
(d, J CF ) 6 Hz), 125.1, 127.6, 128.7, 128.8, 133.0, 142.4 (d, J CF
) 3 Hz), 145.4, 151.7 (d, J CF ) 283 Hz), 151.8 (d, J CF ) 10
Hz). 19F NMR (471 MHz, CDCl3) 31.3 (1F, s) ppm. IR (neat)
2925, 1665, 1595, 1510, 1340, 1110, 855, 750 cm-1. MS (70
eV) m/ z (rel intensity) 339 (M+; 78), 296 (100), 249 (72), 149
(25), 77 (50). HRMS calcd for C19H18N3O2F 339.1383 (M+);
found 339.1394.
Meth yla tion of 4-Bu tyl-3(5)-p h en ylp yr a zole (7a ). 4-Bu-
tyl-1-methyl-3-phenylpyrazole (8a ) and 4-butyl-1-methyl-5-
phenylpyrazole (9a ) were prepared by the method described
for 3a using sodium hydride (18 mg, 62.0% dispersion in
mineral oil, 0.46 mmol), 7a (81 mg, 0.41 mmol), and methyl
iodide (28 µL, 0.45 mmol) in DMF (3 mL). Purification by thin
layer chromatography on silica gel (hexane-ethyl acetate 3:1)
gave 8a and 9a (61 mg, 70%, 8a /9a ) 55/45) as a pale yellow
liquid. 1H NMR (500 MHz, CDCl3, for 6/4 8a /9a mixture) δ
0.83 (1.2H, t, J ) 7.4 Hz), 0.90 (1.8H, t, J ) 7.4 Hz), 1.27 (0.8H,
tq, J ) 7.4, 7.4 Hz), 1.37 (1.2H, tq, J ) 7.4, 7.4 Hz), 1.46 (0.8H,
tt, J ) 7.4, 7.4 Hz), 1.55 (1.2H, tt, J ) 7.4, 7.4 Hz), 2.36 (0.8H,
t, J ) 7.4 Hz), 2.60 (1.2H, t, J ) 7.4 Hz), 3.72 (1.2H, s), 3.88
(1.8H, s), 7.19 (0.6H, s), 7.27-7.32 (1.4H, m), 7.36-7.42 (2.0H,
m), 7.45 (0.8H, tt, J ) 7.3, 1.8 Hz), 7.62 (1.2H, dd, J ) 8.2, 1.2
Hz). 13C NMR (126 MHz, CDCl3) 8a : δ 13.9, 22.5, 24.2, 32.8,
38.8, 119.6, 127.1, 127.7, 128.3, 129.7, 134.4, 149.6; 9a : δ 13.8,
22.3, 23.6, 33.1, 37.1, 120.1, 128.3, 128.6, 129.8, 130.7, 138.1,
140.5 IR (neat) 2920, 2850, 1730, 1605, 1450, 1175, 1025, 990,
780, 700 cm-1. MS (70 eV) m/ z (rel intensity) 8a : 214 (M+;
(2H, t, J ) 7.5 Hz), 4.44 (2H, dddd, J ) 5.3, 1.4, 1.4 Hz, J HF
)
1.4 Hz), 4.99 (1H, ddt, J ) 17.1, 1.4, 1.4 Hz), 5.15 (1H, ddt, J
) 10.2, 1.4, 1.4 Hz), 5.89 (1H, ddt, J ) 17.1, 10.2, 5.3 Hz),
7.28-7.32 (2H, m), 7.42-7.48 (3H, m). 13C NMR (126 MHz,
CDCl3) δ 13.7, 21.3 (d, J CF ) 3 Hz), 22.2, 32.2, 51.7, 102.8 (d,
J CF ) 21 Hz), 117.5, 128.7, 129.0, 129.8, 129.8, 133.5, 142.7,
162.2 (d, J CF ) 244 Hz). 19F NMR (471 MHz, CDCl3) 27.4 (1F,
s) ppm. IR (neat) 2975, 2950, 2875, 1500, 1470, 1220, 995,
925, 770, 705, 670 cm-1. MS (70 eV) m/ z (rel intensity) 258
(M+; 56), 215 (100), 184 (4), 155 (3), 77 (3). Anal. Calcd for
C16H19N2F: C, 74.39; H, 7.41; N, 10.84. Found: C, 74.39; H,
7.55; N, 10.63.
4-Bu t yl-3-flu or o-1-isop r op yl-5-p h en ylp yr a zole (3i).
Compound 3i was prepared by the method described for 3a
using sodium hydride (18 mg, 62.0% dispersion in mineral oil,
0.47 mmol), 4a (91 mg, 0.42 mmol), and isopropyl iodide (46