An efficient one-pot synthesis of pyrazolone derivatives promoted by acidic ionic liquid

Article abstract of DOI:10.1002/cjoc.201180381

A new class of pyrazolone derivatives has been isolated in good to excellent yields from the 2 : 1 condensation reaction between 3-methyl-1-phenyl-5-pyrazolone and arylaldehydes in the presence of ionic liquid [HMIM]HSO₄. The compounds were cha

Full text of DOI:10.1002/cjoc.201180381

NOTE
An Efficient One-pot Synthesis of Pyrazolone Derivatives
Promoted by Acidic Ionic Liquid
Zang, Hongjun*,a(臧洪俊)
Su, Qiuhonga(苏秋红)
Guo, Songa(郭松)
Mo, Yingminga(莫颖明)
Cheng, Bowenb(程博闻)
a Department of Enviromental and Chemistry Engineering, Tianjin Polytechnic University, Tianjin 300160, China
b State Key Laboratory of Hollow Fiber Membrane Materials and Processes, Tianjin 300160, China
A new class of pyrazolone derivatives has been isolated in good to excellent yields from the 2∶ 1 condensation
reaction between 3-methyl-1-phenyl-5-pyrazolone and arylaldehydes in the presence of ionic liquid [HMIM]HSO4.
The compounds were characterised by their IR, NMR spectra, MS and elemental analyses. The important features
of the methodology are a wide application range of substrates, higher yields and shorter reaction time.
Keywords pyrazole, ionic liquid, 3-methyl-1-phenyl-5-pyrazolone, aldehydes
Introduction
context of green synthesis due to their many unique
properties. For example, they have practical non-
volatility, low melting point as well as good electro-
chemical and thermal stability. 1-Methylimidazolium
hydrogen sulfate ([HMIM]HSO4) is a Brφnted acidic
ionic liquid and has been used as catalyst in organic re-
actions.14,15 To the best of our knowledge, there is a lack
of literature on the synthesis of 4-[(5-hydroxy-3-
methyl-1-phenyl-1H-pyrazol-4-yl)-phenyl-methyl]-5-
methyl-2-phenyl-1,2-dihydro-pyrazol-3-ones catalyzed
by [HMIM]HSO4. In continuation of our interest in the
synthesis of heterocyclic compounds, we describe the
synthesis of 4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyra-
zol-4-yl)-phenyl-methyl]-5-methyl-2-phenyl-1,2-dihydro-
pyrazol-3-ones via the reaction between 3-methyl-1-
phenyl-5-pyrazolone and arylaldehydes catalyzed by
ionic liquid [HMIM]HSO4 in ethanol (Scheme 1).
The pyrazole moiety is one of the significant core
structures in natural and unnatural heterocyclic com-
pounds with prominent properties.1 Among pyrazoles,
2,4-dihydro-3H-pyrazol-3-one derivatives are of con-
siderable interests: some are biologically active with
anti-inflammatory, antipyretic, antibacterial, gastric se-
cretion stimulatory, antidepressant, and antifilarial ac-
tivity,2,3 others are important intermediates in organic
synthesis. For instance, aryl-bis(3-methyl-1-phenyl-5-
pyrazol-one-4-yl)methane forms the basis of nitro-
heterocycle to the dipyrazolo diazepine derivative.4
The condensation of aldehydes with 3-methyl-1-
phenyl-5-pyrazolone is a known used route for synthe-
sizing 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols). Acetic
acid or piperidine,5 sodium dodecyl sulfate,6 ETBA7 and
CAN8 can be used as catalysts for this transformation.
The electrocatalytic procedure and solid-state conden-
sation procedure were also applied to the preparation of
4,4'-(arylmethylene)bis(1H-pyrazol-5-ols).9-12 So far,
intensive work has been focused on developing efficient
catalytic systems for conforming to the concept of green
chemistry. Recently, Niknam et al. reported a reaction
for the synthesis of 4,4'-(arylmethylene)bis(1H-pyrazol-
5-ols) through the condensation of aldehydes with
3-methyl-1-phenyl-5-pyrazolone in the presence of sil-
ica-bonded S-sulfonic acid.13 However, the synthesis of
4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-
phenyl-methyl]-5-methyl-2-phenyl-1,2-dihydro-pyrazol-
3-ones 3a—3l from aldehydes and 3-methyl-1-phenyl-5-
pyrazolone has seldom been reported.
Scheme 1
Experimental
All reagents were purchased from Tianjin KEMIOU
Chemical Agents Co., Ltd. and liquid aldehydes were
purified by distillation before use. [HMIM]HSO4,
[BMIM]Cl, [BMIM]Br, [BMIM]BF4 and [BMIM]OAc
were synthesized based on the literature.16,17 Melting
Ionic liquids, especially those based on the imida-
zolium cation, have attracted increasing interest in the
*
E-mail: zanghongjun@tjpu.edu.cn or bowengc@163.com
Received January 7, 2011; revised March 9, 2011; accepted June 28, 2011.
Project supported by the National Natural Science Foundation of China (No. 51076174) and the Tianjin National Natural Science Foundation (No.
11JCZDJC21300).
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Chin. J. Chem. 2011, 29, 2202— 2204

An Efficient One-pot Synthesis of Pyrazolone Derivatives Promoted by Acidic Ionic Liquid
points were measured on an electrothermal apparatus
and were uncorrected.
of stirring at room temperature (41%, Entry 1). To inves-
tigate the effect of [HMIM]HSO4, the synthesis of 3a as a
model was studied with and without [HMIM]HSO4 (Ta-
ble 1, Entryies 2, 7) at the same temperature (75 ℃). Fur-
thermore, other ionic liquids, such as [BMIM]Cl,
[BMIM]Br, [BMIM]BF4 and [BMIM]OAc, were exam-
ined as catalysts for the reaction between 3-methyl-1-
phenyl-5-pyrazolone and benzaldehyde (Table 1, Entryies
3—6). The products were obtained in 72%, 66%, 69% and
68% yields, respectively. It was obvious that [HMIM]-
HSO4 was an efficient catalyst for this transformation.
Subsequently, to show the role of the ratio of the
starting reactants, treatment of 4-chlorobenzaldehyde
with 3-methyl-1-phenyl-5-pyrazolone (molar ratio 1∶1)
was carried out. The mixture of 3b (74%) and the 1∶1
product 4b (22%) was obtained. However, when the
ratio of the starting reactants was 1∶2, 3b was pro-
duced as the single product. The results showed that the
ratio of the starting reactants has effect on the reaction
to some extent. Thus, the 1∶2 ratio of the starting reac-
tants was chosen in the subsequent reactions.
General procedure
To a solution of 1-phenyl-3-methyl-pyrazol-5-one (2
mmol) and [HMIM]HSO4 (10 mol%) in 5 mL ethanol
aromatic aldehyde (1 mmol) was added. The mixture
was stirred at refluxing for an appropriate time. After
the completion of the reaction followed by TLC and
cooling the reaction mixture to room temperature, 20
mL water was added. Then the obtained product was
filtered, dried and if necessary was purified by column
chromatography on silica gel to afford the pure product.
All the known products 3a—3l, 4m were fully charac-
1
terized by IR and H NMR spectroscopy, and melting
points, which were consistent with the literature data.
Rusults and discussion
As shown in Table 1, 3-methyl-1-phenyl-5-pyra-
zolone was treated with benzaldehyde in the presence of
10% of [HMIM]HSO4 in 5 mL ethanol under reflux
condition to afford 3a, which was obtained in higher
yield (81%, Entry 2) in comparsion with the condition
To examine the scope and limitation of this process,
we selected various arylaldehydes and conducted the
reactions in order to synthesize a series of pyrazolone
Table 1 Synthesis of 3a under different conditions
Catalyst loading/% Conditions
10 r.t., stirring
Entry
Catalyst
Time/min
Yield/%
41
1
2
3
4
5
6
7
[HMIM]HSO4
[HMIM]HSO4
[BMIM]Cl
20
20
20
20
20
20
20
10
10
10
10
10
0
reflux at 75 ℃
reflux at 75 ℃
reflux at 75 ℃
reflux at 75 ℃
reflux at 75 ℃
reflux at 75 ℃
81
72
[BMIM]Br
66
[BMIM]BF4
[BMIM]OAc
[HMIM]HSO4
69
68
46
Table 2 The condensation of arylaldehydes with 3-methyl-1-phenyl-5-pyrazolone catalyzed by [HMIM]HSO4 in ethanol under reflux at
75 ℃
m.p./℃
Entry
Ar
Product 3
Time/min
Yield/%
Found
Report
a
b
c
d
e
f
C6H5
3a
3b
3c
3d
3e
3f
20
10
10
10
15
20
15
5
81
88
83
81
77
90
91
80
82
85
93
87
72
167—169
214—215
235—238
226—228
230—232
218—220
153—155
219—221
223—225
158—159
210—212
172—173
193—195
169—17118
214—2118
235—23718
228—23018
229—23118
218—22018
153—15518
221—22218
222—22618
157—15918
210—21318
172—17318
194—19512
4-ClC6H4
2-ClC6H4
2,4-(Cl)2C6H3
2-BrC6H4
4-O2NC6H4
3-O2NC6H4
2-O2NC6H4
2-HOC6H4
4-HOC6H4
2-CH3OC6H4
4-CH3OC6H4
4-(CH3)2NC6H4
g
h
i
3g
3h
3i
35
35
25
35
17
j
3j
k
l
3k
3l
m
4m
Chin. J. Chem. 2011, 29, 2202— 2204
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
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Zang et al.
NOTE
2
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derivatives. The results are listed in Table 2. We found
that the reactions proceeded efficiently and provided the
corresponding products in good to excellent yields. The
substituents (either electron-withdrawing or electron-
donating groups, except p-dimethylamino) on the ben-
zene ring in the arylaldehydes do not significantly affect
neither the yields of the products nor the selectivities.
Although the differences in the reaction times were
slight, generally the electron-withdrawing (nitro groups)
were superior to the electron-donating ones (hydroxyl
groups and methoxy groups) in this regard. When the
condensation of p-(dimethylamino)benzaldehyde with
3-methyl-1-phenyl-5-pyrazolone was carried out under
the same conditions, the reaction mainly gave the 1∶1
product. Similar phenomenon and the reason have been
described in the literatures reported by Li et al. and
Devinder Singh.5,10
4
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Conclusions
In summary, a highly efficient method for the syn-
thesis of 4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-
4-yl)-phenyl-methyl]-5-methyl-2-phenyl-1,2-dihydro-
pyrazol-3-ones through the condensation of 3-methyl-1-
phenyl-5-pyrazolone with arylaldehydes under reflux
conditions has been described. The present methodology
offers several advantages such as short reaction times,
high yields, high selectivity, and easy separation of the
products.
References
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(E1101071 Cheng, F.; Zheng, G.)
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2202— 2204