An eco-friendly one-pot synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) using [Et3NH][HSO4] as a recyclable catalyst

Article abstract of DOI:10.4067/S0717-97072015000300003

A simple and efficient procedure for synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) by one-pot three-component condensation of aromatic aldehydes, ethyl acetoacetate, and phenylhydrazine/hydrazine hydrate under solvent-free conditions in the prese

Full text of DOI:10.4067/S0717-97072015000300003

J. Chil. Chem. Soc., 60, Nº 3 (2015)
AN ECO-FRIENDLY ONE-POT SYNTHESIS OF 4,4′-(ARYLMETHYLENE)BIS(1H-PYRAZOL-5-OLS) USING
[Et3NH][HSO4] AS A RECYCLABLE CATALYST
ZHONGQIANG ZHOU1*, YULIANG ZHANG
College of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan 430074, China
ABSTRACT
A simple and efficient procedure for synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) by one-pot three-component condensation of aromatic aldehydes,
ethyl acetoacetate, and phenylhydrazine/hydrazine hydrate under solvent-free conditions in the presence of [Et NH][HSO4] as catalyst is described. The present
protocol offers several advantages such as using a reusable and cost-effective ionic liquid, high yields, simple p3rocedure, easy work-up and eco-friendly reaction
conditions.
Keywords: 4,4′-(Arylmethylene)bis(1H-pyrazol-5-ols); [Et3NH][HSO4]; Solvent-free; Multicomponent reaction
In green chemistry, elimination of volatile organic solvents in organic
synthesis is a most important goal. Solvent-free conditions makes synthesis
INTRODUCTION
simpler, save energy, and prevent solvent waste, hazards, and toxicity28-29
.
4,4′-(Arylmethylene)bis(1H-pyrazol-5-ols) are applied as fungicides1,
pesticides2 and dyestuffs3. The condensation of aldehydes with two equivalents
of 3-methyl-1-phenyl-5- pyrazolone is a conventional chemical approach to
4,4′-(arylmethylene)bis(1H-pyrazol-5-ols). Many catalysts have been used for
this transformation such as xanthan sulfuric acid4, phosphomolybdic acid5,
silica sulfuric acid6, 3-aminopropylated silica gel7, sodium dodecyl sulfate8,
[Cu(3,4-tmtppa)](MeSO4)4 9, PEG-SO3H10, cellulose sulfuric acid11, lithium
hydroxide monohydrate12, 1,3,5-tris(hydrogensulfato) benzene13, sulfuric acid
([3-(3-silicapropyl)sulfanyl]propyl)ester14, ethylenediammonium diacetate15,
[Sipmim]HSO4 16, TEBA17, ceric ammonium nitrate18, silica-bonded S-sulfonic
acid19, 2-hydroxyethylammonium acetate20, 1,3-disulfonic acid imidazolium
tetrachloroaluminate21 and 1-sulfopyridinium chloride22. Catalyst-free protocol
and the electrocatalytic procedure were also applied to the preparation of
Ionic liquids have been widely used as environmentally benign reaction
media and catalysts in organic synthesis because of their unique properties
of nonvolatility, nonflammability, and recyclability30-31. Recently, the use of
acidic ionic liquid [Et3NH][HSO4] has received considerable attention as a
cheap and easily available reagent in organic reactions 32-37. In continuation of
our work on the application of acidic ionic liquid for development of useful
synthetic methodologies37-38, we report herein, an alternative protocol for the
one-pot three-component synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-
ols) derivatives starting directly from aldehydes, phenylhydrazine/hydrazine
hydrate and ethyl acetoacetate using [Et3NH][HSO ] as an efficient, cost-
effective and recyclable catalyst under solvent-free co4nditions (Scheme 1).
4,4’-(arylmethylene)bis(1H-pyrazol-5-ols)23-26
. All of the aforementioned
EXPERIMENTAL
procedures include two main steps: (1) 3-methyl-1-phenyl-5-pyrazolone should
be synthesized from phenylhydrazine and ethyl acetoacetate firstly27, and (2)
then 3-methyl-1-phenyl-5-pyrazolone reacted with aldehydes. Even though,
4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) could be synthesized by these
methods, most of the methods suffer from limitations such as long reaction
time, use of expensive catalysts, the requirement of special apparatus, tedious
work-up procedures and noncompliance with green chemistry protocols.
Therefore, finding an efficient and eco-friendly protocol for the preparation of
4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) is of obvious importance.
Material and instruments
Melting points were determined on a X-4 micro melting point apparatus
and are uncorrected. FT-IR spectra were obtained as KBr pellets on a Nexus
470 spectrophotometer. 1H NMR spectra were recorded on a Bruker Avance III
400 with TMS as internal standard. All chemicals were commercial products.
[Et3NH][HSO4], [Et3NH][H2PO4], [BPy][HSO4] and [BPy][H2PO4] were
prepared according to the literature method32,38-39
.
General procedure for the synthesis of 4,4′-(arylmethylene)bis(1H-
pyrazol-5-ols)
Scheme 1. [Et3NH][HSO4] catalyzed synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols)
A mixture of aldehyde (5 mmol), ethyl acetoacetate (10 mmol),
4,4′-(Phenylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) (Table 2,
entry 1): H NMR (DMSO-d6, 400 MHz) δ: 2.32 (s, 6H, 2CH3), 4.96 (s, 1H,
CH), 7.17-7.30 (m, 7H, ArH), 7.44 (t, J=7.6 Hz, 4H, ArH), 7.71 (d, J=8.0 Hz,
4H, ArH). IR (KBr) ν: 3358, 3061, 2965, 2582, 1596, 1495, 1414, 1272, 1074,
792, 734, 689 cm-1.
1
phenylhydrazine (10 mmol), and [Et3NH][HSO ] (0.5 mmol) was stirred at 90
°C under solvent-free conditions. The progress4of the reaction was monitored
by TLC using EtOAc/petroleum ether (1/2) as eluent. During the reaction
process, a solid product spontaneously formed. After completion of the
reaction, the reaction mixture was cooled to room temperature. The resulting
solid was recrystallized by using ethanol (95%) to afford the pure product. The
filtrate containing catalyst was evaporated under reduced pressure to give the
catalyst which was used for the next run under similar reaction conditions. All
the products are known and were identified by comparison of their physical
and spectroscopic data with those of authentic samples. The spectral data of
products are given below:
4,4′-[(4-Methylphenyl)methylene]-bis(3-methyl-1-phenyl-1H-pyrazol-5-
1
ol) (Table 2, entry 2): H NMR (DMSO-d6, 400 MHz) δ: 2.24 (s, 3H, CH3),
2.30 (s, 6H, 2CH3), 4.90 (s, 1H, CH), 7.09 (d, J=8.4 Hz, 2H, ArH), 7.13 (d,
J=8.0 Hz, 2H, ArH), 7.24 (t, J=7.2 Hz, 2H, ArH), 7.44 (t, J=7.6 Hz, 4H, ArH),
7.70 (d, J=7.6 Hz, 4H, ArH). IR (KBr) ν: 3413, 3051, 2928, 1604, 1581, 1507,
1414, 1299, 806, 752, 695 cm-1.
4,4′-[(4-Methoxyphenyl)methylene]-bis(3-methyl-1-phenyl-1H-pyrazol-
e-mail: zhou-zq@hotmail.com
2992

J. Chil. Chem. Soc., 60, Nº 3 (2015)
5-ol) (Table 2, entry 3): 1H NMR (DMSO-d6, 400 MHz) δ: 2.32 (s, 6H, 2CH3),
3.72 (s, 3H, CH3O), 4.93 (s, 1H, CH), 6.87 (d, J=8.8 Hz, 2H, ArH), 7.18 (d,
J=8.4 Hz, 2H, ArH), 7.23-7.31 (m, 2H, ArH), 7.45-7.49 (m, 4H, ArH), 7.72-
7.73 (m, 4H, ArH). IR (KBr) ν: 3437, 3068, 2918, 2559, 1606, 1584, 1510,
1411, 1378, 1039, 801, 755 cm-1.
4,4′-[(4-Flurophenyl)methylene]-bis(3-methyl-1-phenyl-1H-pyrazol-5-ol)
(Table 2, entry 4): 1H NMR (DMSO-d6, 400 MHz) δ: 2.32 (s, 6H, 2CH3), 4.96
(s, 1H, CH), 7.09 (t, J=8.0 Hz, 2H, ArH), 7.24-7.32 (m, 4H, ArH), 7.45 (t, J=7.6
Hz, 4H, ArH), 7.72 (d, J=8.0 Hz, 4H, ArH). IR (KBr) ν: 3445, 3080, 288, 1590,
1495, 1401, 1380, 1308, 1121, 902, 842, 788, 690 cm-1.
4,4′-[(3-Methoxyphenyl)methylene]-bis(3-methyl-1-phenyl-1H-pyrazol-
5-ol) (Table 2, entry 5): 1H NMR (DMSO-d , 400 MHz) δ: 2.42 (s, 6H, 2CH3),
3.51 (s, 3H, CH3O), 4.71 (s, 1H, CH), 6.55 6(d, J=8.8 Hz, 2H, ArH), 6.66-6.72
(m, 2H, ArH), 7.89 (m, 1H, ArH), 7.32-7.45 (m, 4H, ArH), 7.73 (m, 4H, ArH).
IR (KBr) ν: 3428, 3085, 2920, 1580, 1508, 1410, 1133, 1025, 804, 685 cm-1.
4,4′-[(3-Nitrophenyl)methylene]bis(3-methyl-1-phenyl-1H-pyrazol-5-ol)
(Table 2, entry 6): 1H NMR (DMSO-d6, 400 MHz) δ: 2.30 (s, 6H, 2CH3), 4.95
(s, 1H, CH), 7.2 (t, J=7.2 Hz, 2H, ArH), 7.37 (t, J=8.0 Hz, 2H, ArH), 7.44 (t,
J=8.8 Hz, 2H, ArH), 7.67 (d, J=8.0 Hz, 4H, ArH), 8.07 (d, J=6.4 Hz, 4H, ArH).
IR (KBr) ν: 3078, 2918, 1599, 1523, 1502, 1346, 1269, 1093, 758, 734, 696
cm-1.
4,4′-(Phenylmethylene)bis(3-methyl-1H-pyrazol-5-ol) (Table 2, entry 16):
1H NMR (DMSO-d6, 400 MHz) δ: 2.07 (s, 6H, 2CH3), 4.82 (s, 1H, CH), 7.09-
7.14 (m, 3H, ArH), 7.19-7.22 (m, 2H, ArH). IR (KBr) ν: 3296, 2971, 1612,
1522, 1494, 1380, 1049, 825, 778, 717 cm-1.
4,4′-[(3-Nitrophenyl)methylene]bis(3-methyl-1H-pyrazol-5-ol) (Table 2,
1
entry 17): H NMR (DMSO-d6, 400 MHz) δ: 2.11 (s, 6H, CH3), 4.99 (s, 1H,
CH), 7.54-7.57 (m, 2H, ArH), 7.96 (s, 1H, ArH), 8.03 (s, 1H, ArH). IR (KBr):
3419, 2961, 1599, 1447, 1390, 1182, 837, 795, 764 cm-1.
4,4′-[(4-Chlorophenyl)methylene]bis(3-methyl-1H-pyrazol-5-ol) (Table
2, entry 18): 1H NMR (DMSO-d , 400 MHz) δ: 2.08 (s, 6H, CH3), 4.82 (s, 1H,
CH), 7.12 (s, 2H, ArH), 7.27 (m,62H, ArH). IR (KBr): 3437, 1614, 1488, 1388,
1094, 757 cm-1.
4,4′-[(4-Hydroxyphenyl)methylene]bis(3-methyl-1H-pyrazol-5-ol) (Table
2, entry 19): 1H NMR (DMSO-d6, 400 MHz) δ: 2.06 (s, 6H, CH3), 4.71 (s, 1H,
CH), 6.58 (d, J=8.4 Hz, 2H, ArH), 6.90 (d, J=8.4 Hz, 2H, ArH), 9.04(s, 1H). IR
(KBr): 3266, 1561, 1514, 1466, 1400, 1174, 872, 786, 731 cm-1.
RESULTS AND DISCUSSION
Inordertooptimizethereactionconditions,thereactionofphenylhydrazine,
ethyl acetoacetate and 2,4-dichlorobenzaldehyde was selected as a model
reaction. The reactions catalyzed by various ionic liquids were carried out
under solvent-free conditions at 50 °C. The product was obtained in 65%, 31%,
42% and 31% yield, respectively (Table 1, entries 1-4). The results clearly
showed that [Et3NH][HSO ] was an effective catalyst for this condensation.
Then the reaction tem4perature was examined and 90 °C was found to be
the optimum temperature. Reducing the temperature from 90 °C led to a longer
reaction time. Raising the reaction temperature from 90 to 100 °C did not
increase the yield and also did not improve the reaction rate. We also evaluated
the amount of catalyst required for this transformation using 5 mol% and we
obtained 69% yield. Maximum yield (86%) was obtained when the reaction
was carried out with 10 mol% of the catalyst. Any further increase of catalyst
loading does not affect the yield (Table 1, entry 12). So, the optimum amount
of [Et NH][HSO4] was found to be 10 mol% relative to reactants. The catalyst
plays 3a crucial role in the reaction. The condensation reaction gave very low
yield in the absence of catalyst (Table 1, entry 10).
4,4′-[4-Hydroxy-3-methoxyphenyl)methylene]-bis(3-methyl-1-phenyl-
1
1H-pyrazol-5-ol) (Table 2, entry 7): H NMR (DMSO-d6, 400 MHz) δ: 2.33
(s, 6H, 2CH3), 3.69 (s, 3H, CH3O), 4.87 (s, 1H, CH), 6.71-6.74 (m, 2H, ArH),
6.88-6.89 (m, 1H, ArH), 7.24-7.26 (m, 2H, ArH), 7.43-7.47 (m, 4H, ArH),
7.72-7.74 (m, 4H, ArH), 8.81 (s, 1H, OH). IR (KBr) ν: 3213, 3071, 2561, 1609,
1507, 1422, 1264, 1131, 1044, 816, 789, 760, 693 cm-1.
4,4′-[(2-Chlorophenyl)methylene]-bis(3-methyl-1-phenyl-1H-pyrazol-5-
1
ol) (Table 2, entry 8): H NMR (DMSO-d6, 400 MHz) δ: 2.29 (s, 6H, 2CH3),
5.14 (s, 1H, CH), 7.22-7.33 (m, 4H, ArH), 7.41 (d, J=8.0 Hz, 1H, ArH), 7.46
(t, J=7.6 Hz, 4H, ArH), 7.70 (d, J=8.0 Hz, 4H, ArH), 7.80 (d, J=7.2 Hz, 1H,
ArH). IR (KBr) ν: 3435, 3066, 2916, 1615, 1562, 1503, 1404, 1374, 1310, 839,
752, 695 cm-1.
4,4′-[(4-Chlorophenyl)methylene]-bis(3-methyl-1-phenyl-1H-pyrazol-5-
1
ol) (Table 2, entry 9): H NMR (DMSO-d6, 400 MHz) δ: 2.30 (s, 6H, 2CH3),
4.98 (s, 1H, CH), 7.22-7.28 (m, 4H, ArH), 7.35 (d, J=8.4 Hz, 2H, ArH), 7.44
(t, J=8.0 Hz, 4H, ArH), 7.71 (d, J=8.0 Hz, 4H, ArH). IR (KBr) ν: 3432, 3068,
2924, 1601, 1496, 1412, 1296, 1196, 1094, 1019, 835, 752, 691 cm-1.
4,4′-[(4-Bromophenyl)methylene]bis(3-methyl-1-phenyl-1H-pyrazol-5-
ol) (Table 2, entry 10): 1H NMR (DMSO-d6, 400 MHz) δ: 2.32 (s, 6H, 2CH3),
4.95 (s, 1H, CH), 7.19-7.27 (m, 4H, ArH), 7.42-7.48 (m, 6H, ArH), 7.70 (d,
J=8.0 Hz, 4H, ArH). IR (KBr) ν: 3422, 3066, 2922, 2546, 1598, 1484, 1407,
1293, 1013, 809, 747, 687 cm-1.
4,4′-[(2,4-Dichlorophenyl)methylene]bis(3-methyl-1-phenyl-1H-pyrazol-
5-ol) (Table 2, entry 11): 1H NMR (DMSO-d6, 400 MHz) δ: 2.28 (s, 6H, 2CH3),
5.09 (s, 1H, CH), 7.25 (t, J=7.2 Hz, 2H, ArH), 7.40-7.46 (m, 5H, ArH), 7.56 (d,
J=2.0 Hz, 1H, ArH), 7.69 (d, J=8.0 Hz, 4H, ArH), 7.75 (d, J=8.4 Hz, 1H, ArH).
IR (KBr) ν: 3425, 3060, 2919, 1595, 1573, 1498, 1471, 1380, 1295, 1105, 843,
754, 690 cm-1.
To compare the efficiency as well as capacity of the solvent-free conditions
with respect to solution conditions, various solvents were examined. The
results showed that reactions in solvents take more time and also the yields
are low compared to the solvent-free conditions (Table 1, entries 13-18). Water
has been identified as an ideal solvent because it is abundant, inexpensive,
non-flammable and environmentally benign 40,41. However, when the reaction
was carried out in water, the expected product was obtained only in 18% yield
after 2 h. This may be explained due to the decreased diffusion of the reactant
molecules in the presence of the solvent. Considering the importance of green
chemistry, the solvent-free reaction conditions are the advantageous aspect of
the present method, since it avoids the use of environmental hazardous and
toxic solvents.
4,4′-[(4-Nitrophenyl)methylene]-bis(3-methyl-1-phenyl-1H-pyrazol-5-ol)
1
(Table 2, entry 12): H NMR (DMSO-d , 400 MHz) δ: 2.28 (s, 6H, 2CH3),
In order to establish the generality, the catalyst was successfully applied to
the reaction by using different aromatic aldehydes with a wide range of ortho-,
meta- and para-substitutions under the optimized reaction conditions. The
results are summarized in Table 2. It is clear from this table that, high product
yields were obtained with aromatic aldehydes containing electron-donating
and electron-withdrawing substituents. Furthermore, the reaction is compatible
in the presence of various functional groups such as -Cl, -OCH3, -NO2 and
-OH. When changing phenylhydrazine into hydrazine hydrate, a similar result
was given; the reaction gave the corresponding compounds in good yields.
The possibility of recycling the catalyst was examined using the reaction
of benzaldehyde, ethyl acetoacetate, and hydrazine hydrate under the
optimized reaction conditions. After completion of the reaction, the reaction
mixture was cooled to room temperature. The resulting solid was purified by
recrystallization from ethanol (95%). The filtrate (consisting of ethanol, acidic
ionic liquid and some other residual reactants or by-products) was further
evaporated under reduced pressure to dryness and the resulting catalyst was
reused directly for the next run without any further treatment. As can be seen
from Table 3, the catalyst was reused for successive reaction at least six times
without any appreciable loss of catalytic activity.
5.06 (s, 1H, CH), 7.18 (t, 2H, J=7.2 Hz,6ArH), 7.38 (t, J=7.2 Hz, 4H, ArH),
7.45 (d, J=8.4 Hz, 2H, ArH), 7.64 (d, J=8.0 Hz, 4H, ArH), 8.10 (d, J=8.8 Hz,
2H, ArH). IR (KBr) ν: 3423, 3071, 2925, 1599, 1518, 1502, 1348, 1299, 835,
759, 693 cm-1.
4,4′-[(2-Hydroxyphenyl)methylene]-bis(3-methyl-1-phenyl-1H-pyrazol-
5-ol) (Table 2, entry 13): 1H NMR (DMSO-d , 400 MHz) δ: 2.28 (s, 6H, 2CH ),
5.16 (s, 1H, CH), 6.70-6.74 (m, 2H, ArH), 6.696 (t, J=7.2 Hz, 1H, ArH), 7.22 3(t,
J=7.2 Hz, 2H, ArH), 7.42 (t, J=8.0 Hz, 4H, ArH), 7.57 (d, J=7.2 Hz, 1H, ArH),
7.71 (d, J=7.8 Hz, 4H, ArH). IR (KBr) ν: 3427, 3066, 2928, 2832, 1603, 1578,
1501, 1454, 1372, 1231, 754, 690 cm-1.
4,4′-[(4-Hydroxyphenyl)methylene]bis(3-methyl-1-phenyl-1H-pyrazol-5-
ol) (Table 2, entry 14): 1H NMR (DMSO-d6, 400 MHz) δ: 2.30 (s, 6H, 2CH3),
4.84 (s, 1H, CH), 6.66 (d, J=8.8 Hz, 2H, ArH), 7.04 (d, J=8.8 Hz, 2H, ArH),
7.22-7.26 (t, J=7.2 Hz, 2H, ArH), 7.44 (t, J=8.0 Hz, 4H, ArH), 7.71 (d, J=8.0
Hz, 4H, ArH), 9.16 (s, 1H, OH). IR (KBr) ν: 3413, 3158, 2969, 1597, 1502,
1427, 1275, 819, 756, 692 cm-1.
4,4′-[(2-Methoxyphenyl)methylene]-bis(3-methyl-1-phenyl-1H-pyrazol-
5-ol) (Table 2, entry 15): 1H NMR (DMSO-d , 400 MHz) δ: 2.26 (s, 6H, 2CH3),
3.79 (s, 3H, OCH ), 5.18 (s, 1H, CH), 6.82-66.93 (m, 2H, ArH), 7.11-7.24 (m,
3H, ArH), 7.41 (t,3J=7.2 Hz, 4H, ArH), 7.60 (d, J=7.6 Hz, 1H, ArH), 7.67-7.70
(m, 4H, ArH). IR (KBr) ν: 3427, 3062, 2922, 1598, 1575, 1497, 1241, 756 cm-1.
2993

J. Chil. Chem. Soc., 60, Nº 3 (2015)
Table 1 Effect of different reaction conditions on ionic liquids catalyzed synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) a
Catalyst loading
(mol%)
Time
(min)
Yieldb
(%)
Entry
Catalyst
Solvent
Temperature (°C)
1
2
[Et3NH][HSO4]
[Et3NH][H2PO4]
[BPy][HSO4]
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
THF
50
50
10
10
10
10
10
10
10
10
10
0
180
180
180
180
160
90
65
31
3
50
42
4
[BPy][H2PO4]
[Et3NH][HSO4]
[Et3NH][HSO4]
[Et3NH][HSO4]
[Et3NH][HSO4]
[Et3NH][HSO4]
No catalyst
50
31
5
60
80
6
70
85
7
80
55
85
8
90
35
86
9
100
90
35
86
10
11
12
13
14
15
16
17
18
210
35
7
[Et3NH][HSO4]
[Et3NH][HSO4]
[Et3NH][HSO4]
[Et3NH][HSO4]
[Et3NH][HSO4]
[Et3NH][HSO4]
[Et3NH][HSO4]
[Et3NH][HSO4]
90
5
69
90
20
10
10
10
10
10
10
35
86
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
120
120
120
120
120
120
trace
trace
34
CH3CN
CHCl3
C6H6
33
C2H5OH
15
H2O
18
a Reaction condition: 2,4-dichlorobenzaldehyde (5 mmol), ethyl acetoacetate (10 mmol), phenylhydrazine (10 mmol), solvent (10 mL).
b Isolated yield.
Table 2 [Et3NH][HSO4] catalyzed synthesis of 4,4′-(arylmethylene)bis (1H-pyrazol-5-ols) a
Mp. (°C)
Entry
R1
R2
Time (min)
Yield b (%)
Found
Reported
170-1726
201-20313
173-17524
182-18413
180-1825
149-1508
196-19717
235-23713
213-21521
183-18513
227-22913
219-2209
218-2205
154-15713
211-21413
230-2328
271-2728
224-2268
262-2648
1
2
C6H5
4-CH3C6H4
4-CH3OC6H4
4-FC6H4
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
H
45
30
30
30
35
25
30
30
30
25
35
45
30
30
45
30
20
25
20
90
92
97
83
90
82
93
90
87
91
86
79
90
97
92
93
87
88
84
171-172
201-203
172-174
181-183
181-183
151-153
195-197
236-238
215-216
201-203
227-229
217-219
222-224
161-163
210-211
229-231
272-274
223-225
263-265
3
4
5
3-CH3OC6H4
3-NO2C6H4
4-HO-3-MeOC6H3
2-ClC6H4
6
7
8
9
4-ClC6H4
10
11
12
13
14
15
16
17
18
19
4-BrC6H4
2,4-Cl2C6H3
4-NO2C6H4
2-HOC6H4
4-HOC6H4
2-CH3OC6H4
C6H5
3-NO2C6H4
4-ClC6H4
H
H
4-HOC6H4
H
a Reaction condition: aldehyde (5 mmol), ethyl acetoacetate (10 mmol), phenylhydrazine/ hydrazine hydrate (10 mmol), [Et3NH][HSO4] (0.5 mmol) at 90 °C
under solvent-free conditions.
b Isolated yield.
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J. Chil. Chem. Soc., 60, Nº 3 (2015)
Table 3 Recycling of the [Et3NH][HSO4] a
CONCLUSION
Run
1
Time (min)
Yieldb (%)
In summary, this paper describes a convenient and efficient process
for the solvent-free synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols)
through the three-component coupling of aldehydes, ethyl acetoacetate and
phenylhydrazine/hydrazine hydrate using [Et NH][HSO ] as a recyclable
catalyst. High yields of products, short reacti3on time, e4asily available and
cheap catalyst, simple experimental and isolation procedures, eco-friendly
reaction conditions make this methodology a valid contribution to the existing
processes in the field of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives
synthesis.
30
30
30
30
30
30
30
92
92
91
93
92
87
88
2
3
4
5
6
ACKNOWLEDGEMENTS
7
We thank the Natural Science Foundation of Hubei Province (grant No.
2007ABA291) for financial support.
a
Reaction condition: benzaldehyde (5 mmol), ethyl acetoacetate (10
mmol), hydrazine hydrate (10 mmol), [Et3NH][HSO4] (0.5 mmol) at 90 °C
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