3206 Min et al.
Asian J. Chem.
R2
CDCl3) δ: 2.29 (s, 3H, CH3), 2.39 (s, 3H, CH3), 6.06 (s, 1H,
CH), 7.66 (d, 2H, J = 5.6 Hz, ArH), 8.30 (d, 2H, J = 5.6 Hz,
ArH); IR (KBr, νmax, cm-1): 3102, 2977, 1660, 1103, 852; ESI-
MS: 218 ([M + H]+).
(3,5-Dimethyl-1H-pyrazol-1-yl)(phenyl)methanone
(Table-2, entry 7)4a: Yellow oil; 1H NMR (400 MHz, CDCl3)
δ: 2.27 (s, 3H, CH3), 2.68 (s, 3H, CH3), 6.07 (s, 1H, CH),
7.45-7.56 (m, 3H, ArH), 7.98 (d, 2H, J = 7.2 Hz, ArH); IR
(KBr, νmax, cm-1): 3058, 2977, 2926, 1698, 1342, 709; ESI-
MS: 201 [M + H]+.
3-Butyl-6-(3,5-dimethyl-1H-pyrazol-1-yl)isobenzofu-
ran-1(3H)-one(Table-2, entry 8): Yellow oil; 1H NMR (400
MHz, CDCl3) δ: 0.92 (t, 3H, J = 14.2 Hz, CH3), 1.34-1.53 (m,
4H, 2CH2), 1.76-1.85 (m, 1H, CHH), 2.04-2.14 (m, 1H, CHH),
2.30 (s, 3H, CH3), 2.37 (s, 3H, CH3), 5.52-5.55 (m, 1H, CH),
6.05 (s, 1H, CH), 7.53(d, 1H, J = 8.1 Hz, ArH), 7.85-7.88 (m,
2H,ArH); 13C NMR (400 MHz, CDCl3) δ: 12.55, 13.45, 13.83,
22.39, 26.75, 34.33, 81.36, 107.94, 120.40, 122.67, 127.09,
N
glycerol-water
R2
90°C
O
O
N
NHNH2
R1
R1
R2
R2
O
O
glycerol-water
O
O
N
N
R2
NHNH2
R2
R2
90°C
R2
R1=H, 4-Cl, 4-CH3, 4-nitro, 2, 4-dinitro, furanone group, R2= CH3, (CH3)2CH
Scheme-I
(ppm) down field from tetramethyl silane (TMS) as the internal
standard. Mass spectra were recorded on an Agilent 1100 LC/
MSD Trap. The starting material, 3-n-butyl-6-hydrazinyliso-
benzofuran-1(3H)-one (Table-2, entry 8), was synthesized
according to the literature method10.
General procedure: Glycerol (2 mL) was dissolved in
water (2 mL), then phenylhydrazine derivative (1 mmol) was
added under stirring and the reaction mixture was heated to
90 °C followed by addition of 1,3-dicarbonyl compounds
(1 mmol). The progress of reaction was monitored by TLC.
When all the starting material had been consumed, the mixture
was cooled to room temperature and extracted with ethyl
acetate (2 × 5 mL). The organic phase was separated and dried
over anhydrous Na2SO4 and evaporated under reduced pressure
to give crude product. The pure product was isolated by silica
gel column chromatography to give the product as a yellow
oil or powder. Data of some compounds are shown below:
3,5-Dimethyl-1-phenyl-1H-pyrazole (Table-2, entry
1)4d: Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 2.28 (s, 3H,
CH3), 2.29 (s, 3H, CH3), 6.01(s, 1 H, CH), 7.30-7.43 (m, 5H,
ArH); IR (KBr, νmax/cm-1): 3057, 2978, 1342, 1045, 712; ESI-
MS: 173 ([M + H]+).
130.54, 139.62, 140.95, 148.28, 149.84, 169.72; IR (KBr, νmax
,
cm-1): 3076, 2982, 1749, 1613, 743; ESI-MS: 285 [M + H]+.
RESULTS AND DISCUSSION
Initially, we carried out the reaction between phenyl hydra-
zine and acetylacetone using aqueous glycerol as a solvent to
afford 1-phenyl-3,5-dimethypyrazole. A mixture of phenyl
hydrazine (1 mmol) and acetylacetone (1 mmol) in aqueous
glycerol was stirred at room temperature. It was observed that
the starting materials were consumed after long reaction time
as indicated by TLC analysis. To optimize the reaction condi-
tions to afford the desired pyrazole in good yield, the same
reaction was conducted at different temperature and it was
observed that as temperature increases, rate of reaction increases
and good amount of yield was obtained at 90 °C.At this tempe-
rature, different glycerol-water mixtures were used as solution,
the best yield was obtained within 30 min as the solvent mixed
in a 1:1 volume ratio (Table-1, entry 3). we also executed the
same reaction in absence of water or glycerol, but the yield of
the product decreased. For comparison, the reaction was perfor-
med in ethanol catalyzed. by hydrochloric acid (Table-1, entry
6), The results indicated that although the reaction in the
glycerol-water (1:1) proceeded more slowly than that in ethanol,
the yield was similar, importantly, the former didn't need acid
as a catalyst. Thus the glycerol-water (1:1) was a suitable
solvent for this transformation. Again the advantage of this
protocol was, after the work-up procedure, glycerol-water
system was successfully recovered and reused for another
reaction without affecting the yields.
3,5-Diisopropyl-1-phenyl-1H-pyrazole (Table-2, entry
2): Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 1.17 (d, 6H, J =
4.6 Hz, 2CH3), 1.30 (d, 6H, J = 4.7 Hz, 2CH3), 2.99-3.04 (m,
2H, 2CH), 6.04 (s, 1 H, CH), 7.33-7.44 (m, 5H, ArH); 13C
NMR (400 MHz, CDCl3) δ: 22.92, 25.48, 27.92, 99.51, 125.90,
127.65, 129.00, 140.23, 150.65, 159.19; IR (KBr, νmax, cm-1):
3057, 2986, 1340, 1041, 728; ESI-MS: 229 ([M+H]+).
1-(2,4-Dinitrophenyl)-3,5-dimethyl-1H-pyrazole
(Table-2, entry 3)4a: Yellow solid, m.p. 120-122 °C; 1H NMR
(400 MHz, CDCl3) δ: 2.26 (s, 3H, CH3), 2.27 (s, 3H, CH3),
6.11 (s, 1H, CH), 7.70 (d, 1H, J = 5.6 Hz, ArH), 8.54 (dd, 1H,
J1 = 5.8 Hz, J2 = 1.6 Hz, ArH), 8.80 (s, 1H, ArH); IR (KBr,
ν
max, cm-1): 3120, 3077, 2928, 1612, 1532, 1124, 671; ESI-
MS: 263 ([M + H]+).
3,5-Dimethyl-1-p-tolyl-1H-pyrazole (Table-2, entry 4)4d:
Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 2.28 (s, 3H, CH3),
2.30 (s, 3H, CH3), 2.39 (s, 3H, CH3), 5.98 (s, 1 H, CH), 7.24
(d, 2H, J = 5.4 Hz, 2ArH), 7.29 (d, 2H, J = 5.6 Hz, 2 ArH);
(KBr, νmax, cm-1): 3054, 2975, 2928, 1342, 712; ESI-MS: 187
([M + H]+).
1-(4-Chlorophenyl)-3,5-dimethyl-1H-pyrazole (Table-
2, entry 5)4d: Yellow oil; 1H NMR (400 MHz, CDCl3) δ: 2.29
(s, 3H, CH3), 2.30 (s, 3H, CH3), 6.01 (s, 1 H, CH), 7.37-7.42
(m, 4H, ArH); (KBr, νmax, cm-1): 3079, 2985, 1109, 709; ESI-
MS: 207 ([M + H]+).
TABLE-1
SCREENING FOR OPTIMAL REACTION CONDITIONS
Entry
Solvent
Time (min)
Yield (%)
1
2
3
Glycerol
45
40
30
43
48
20
85
92
95
82
70
94
Glycerol:H2O (2:1)
Glycerol:H2O (1:1)
Glycerol:H2O (1:2)
Glycerol:H2O (1:4)
C2H5OH
4
5
6a
3,5-Dimethyl-1-(4-nitrophenyl)-1H-pyrazole (Table-2,
aCatalyzed by hydrochloric acid
entry 6)4a: Yellow solid, m.p. 100-101 °C; 1H NMR (400 MHz,