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U. Yunus et al. / Journal of Molecular Structure 995 (2011) 173–180
OH
2
N
2
N
CH3
H3C
1
N
1
N
HO
3
3
5
5
4
4
R
R
R = H, 2-OCH3, 4-OCH3
Fig. 1. General structure and numbering scheme of synthesized regioisomeric pyrazoles.
2.2.1. General procedure for the preparation of 1,3,5-trisubstituted
pyrazoles (7/9 a,b)
37.38; MS m/z (%) 250.4 (M+, 100), 222.3 (23), 207.3 (23), 178
(30), 152 (13), 118.2 (70), 91.1 (10), 77.1 (23), 51 (8).
0.5 mol of b-diketone (4,6) was dissolved in ethanol (130 mL) in
a round bottom flask fitted with a reflux condenser. When all the b-
diketone was dissolved, 0.5 mol of methyl hydrazine was added
drop wise. After the addition of methyl hydrazine, the reaction
mixture was refluxed for 6 h. The major isomer 7/9 was separated
as soon as formed as fine crystals which was filtered and recrystal-
lized from ethanol. The filtrate was concentrated and the crude so-
lid was purified by column chromatography, which gave the minor
isomer 7/9b, which was recrystallized from ethanol.
2.2.1.3. 1-Methyl-5-(20-hydroxyphenyl)-3-(400-methoxyphenyl)pyra-
zole (9a). Yield 54%; m.p. 160–162 °C; Rf value 0.11 (1,2-dichloro-
ethane); FT-IR (KBr cmꢀ1) 3620 (OH), 1640 (C@N), 1607 (C@C),
1365 (CAN), 1250 (OCH3); 1H NMR (DMSO, d ppm) 9.89 (s, 1H,
ArAOH), 7.74–6.69 (m, 8H, ArAH), 6.58 (s, 1H, pyrazole-H4), 3.76
(s, 3H, OCH3), 3.69 (s, 3H, NCH3); 13C NMR (DMSO, d ppm)
158.63, 154.95, 148.67, 141.88, 131.21 (2C), 130.24, 126.29,
126.18, 119.10, 117.48, 115.93, 113.97, 103.02, 54.01, 37.05; MS
m/z (%) 280 (M+, 100), 237 (21), 193.9 (6), 165 (24), 146 (14),
139 (11), 118 (12), 77 (27), 63 (33).
2.2.1.1. 1-Methyl-5-(20-hydroxyphenyl)-3-phenylpyrazole (7a). Yield
53%; m.p. 163–165 °C; Rf value 0.13 (1,2-dichloroethane); FT-IR
(KBr cmꢀ1) 3605 (OH), 1629 (C@N); 1615 (C@C), 1364 (CAN); 1H
NMR (DMSO, d ppm) 9.95 (s, 1H, ArAOH), 7.33–6.91 (m, 9H, ArAH),
6.69 (s, 1H, pyrazole-H4); 3.72 (s, 3H, NCH3): 13C NMR (DMSO, d
ppm) 155.02, 148.78, 142.07, 133.57, 131.28, 130.38, 128.59 (2C),
127.21, 124.93 (2C), 119.16, 117.39, 115.96, 103.66, 37.22; MS
m/z (%) 250.2 (M+, 100), 224 (30), 205 (20), 178 (35), 153 (13),
118 (75), 91 (5), 77 (25), 51 (9).
2.2.1.4. 1-Methyl-3-(20-hydroxyphenyl)-5-(400-methoxyphenyl)pyra-
zole (9b). Yield 7%; m.p. 95–97 °C; Rf value 0.81 (1,2-dichloroeth-
ane); FT-IR (KBr cmꢀ1) 3610 (OH), 1640 (C@N), 1600 (C@C), 1364
(CAN), 1230 (OCH3); 1H NMR (DMSO, d ppm) 10.88 (s, 1H, ArAOH),
7.56–6.86 (m, 8H, ArAH), 6.59 (s, 1H, pyrazole-H4), 3.85 (s, 3H,
OCH3), 3.58 (s, 3H, NCH3); 13C NMR (DMSO, d ppm) 160.10,
155.95, 150.27, 144.46, 130.09 (2C), 128.93, 126.13, 122.19,
119.15, 116.97, 116.64, 114.23 (2C), 102.10, 55.35, 37.32; MS m/z
(%) 280 (M+, 100), 265 (46), 252 (10), 237 (12), 165 (17), 148
(55), 140 (32), 118 (9), 77 (6).
2.2.1.2. 1-Methyl-3-(20-hydroxyphenyl)-5-phenylpyrazole (7b). Yield
17.4%; m.p. 98–100 °C; Rf value 0.69 (1,2-dichloroethane); FT-IR
(KBr cmꢀ1) 3620 (OH), 1630 (C@N), 1610 (C@C), 1370 (CAN); 1H
NMR (DMSO, d ppm) 10.88 (s, 1H, ArAOH), 7.58–6.91 (m, 9H,
ArAH), 6.65 (s, 1H, pyrazole-H4), 3.88 (s, 3H, NCH3): 13C NMR
(DMSO, d ppm) 155.92, 150.31, 144.61, 129.86, 128.98, 128.89,
128.75 (2C), 127.93, 126.14, 119.17, 116.97, 116.53, 102.42,
2.2.2. Preparation of 1,3,5 –trisubstituted pyrazoles (8a,b)
0.5 mol of b-diketone 5 was dissolved in ethanol (130 mL) in a
round bottom flask fitted with a reflux condenser and 3 mL of gla-
cial acetic acid was added. When the whole b-diketone was dis-
Table 1
Crystal data and structure refinements for compounds 7a, 7b, 8b and 10.
Compound 7a
Compound 7b
Compound 8b
Compound 10 [25]
Empirical formula
Formula weight
Crystal shape (colour)
Crystal system
Space group
Unit cell dimension
a (Å)
C
16H14N2O
C16H14N2O
250.29
Block (colourless)
Monoclinic
Pꢁ21/c
C17H16N2O2
280.32
Block (colourless)
Monoclinic
Pꢁ21/n
C16H14N2O2
266.29
Block (yellow)
Orthorhombic
Pꢁ2c–2n
250.29
Block (yellow)
Orthorhombic
Pꢁ21ꢁ21ꢁ21
4.6677(4)
12.3866(10)
21.6888(18)
90.00
90.00
90.00
1253.98(18)
4
1.326
10.3020(8)
6.9323(6)
18.6692(15)
90.00
100.2200(10)
90.00
1312.14(19)
4
1.267
10.4877(7)
12.4162(8)
11.4276(8)
90.00
96.9640(10)
90.00
1477.09(17)
4
1.261
17.5093(16)
10.1881(9)
7.4386(7)
90.00
90.00
90.00
1326.9(2)
4
1.333
b (Å)
c (Å)
a
(°)
b (°)
(°)
c
3
V (Å
)
Z
Dcalc (g cmꢀ3
)
Crystal size (mm)
F(0 0 0)
0.32 ꢂ 0.28 ꢂ 0.25
0.32 ꢂ 0.28 ꢂ 0.24
0.28 ꢂ 0.26 ꢂ 0.24
0.32 ꢂ 0.26 ꢂ 0.25
528
528
592
560
Total reflections
Goodness-of-fit
1812
1.069
3170
0.990
3602
1.026
1735
1.071
h Range for data collection (°)
2.50–28.28
2.72–28.28
2.43–28.33
3.07–28.25