Rapid microwave-enhanced synthesis of 1-phenyl-3-methyl-5-Acyloxypyrazoles under solvent-free conditions

Article abstract of DOI:10.1081/SCC-120005938

The microwave-enhanced synthesis of 5-acyloxypyrazoles from 1-phenyl-3-methylpyrazole-5-one and acid chlorides under solvent-free conditions has been achieved in moderate to good yield.

Full text of DOI:10.1081/SCC-120005938

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RAPID MICROWAVE-ENHANCED SYNTHESIS OF 1-
PHENYL-3-METHYL- 5-ACYLOXYPYRAZOLES UNDER
SOLVENT-FREE CONDITIONS
a
a
a
a
Yinjuan Bai , Jun Lu , Haiying Gan & Zhenjun Wang
a
Department of Chemistry , Northwest University , Xi'an, 710069, P.R. China
Published online: 16 Aug 2006.
To cite this article: Yinjuan Bai , Jun Lu , Haiying Gan & Zhenjun Wang (2002) RAPID MICROWAVE-ENHANCED SYNTHESIS OF
-PHENYL-3-METHYL- 5-ACYLOXYPYRAZOLES UNDER SOLVENT-FREE CONDITIONS, Synthetic Communications: An International
1
Journal for Rapid Communication of Synthetic Organic Chemistry, 32:16, 2549-2553, DOI: 10.1081/SCC-120005938
To link to this article: http://dx.doi.org/10.1081/SCC-120005938
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 16, pp. 2549–2553, 2002
RAPID MICROWAVE-ENHANCED
SYNTHESIS OF 1-PHENYL-3-METHYL-
5
-ACYLOXYPYRAZOLES UNDER
SOLVENT-FREE CONDITIONS
Yinjuan Bai,* Jun Lu,Haiying Gan,
and Zhenjun Wang
Department of Chemistry, Northwest University,
Xi’an 710069, P.R. China
ABSTRACT
The microwave-enhanced synthesis of 5-acyloxypyrazoles
from 1-phenyl-3-methylpyrazole-5-one and acid chlorides
under solvent-free conditions has been achieved in moderate
to good yield.
Key Words: Microwave irradiation; Acylation; 1-Phenyl-3-
methylpyrazole-5-one
Microwave irradiation has been employed for the synthesis of a wide
variety of organic molecules. The benefit of microwave irradiation includes
reduction of reaction time, higher yields, greater selectivity, cleaner reaction
products and easier manipulation. Therefore, the application of microwave
irradiation in organic synthesis has been the focus of considerable attention
[
1,2]
in recent years and is becoming an increasingly popular technology.
*
Corresponding author. Fax: 86-29-8303798; E-mail: baiyinjuan@hotmail.com
549
2
DOI: 10.1081/SCC-120005938
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
2
550
BAI ET AL.
Reactions in ‘‘dry media’’ or under solvent-free conditions are especially
appealing as they provide an opportunity to work with open vessels, thus
avoiding the risk of high pressure development and with the possibility of
upscaling the reactions to larger scale. Solventless procedures without the
[
3,4]
use of supporting reagents are particularly eco-friendly.
Acyl derivatives of 1-phenyl-3-methylpyrazole-5-one are very attrac-
tive compounds. Certain acyl pyrazolones as well as their complexes have
[
5]
[6]
biological activities, such as antiviral, antiinflamatary, herbicidal and
[
7]
growth-regulating activities. Meanwhile, the 4-acylderivatives, as b-dike-
tone reagents, are widely used as chelating agents for preparation of coor-
[
8]
dination compounds,
and they have been extensively studied as
[
9]
extractants for the actinides, lanthanides and alkali-earth metals. Under
normal conditions, acylation of 1-phenyl-3-methylpyrazole-5-one with 1 mol
acid chlorides or anhydrides in the presence of calcium hydroxide in ethanol
or dioxoane gives the 4-acylderivatives,
solvent, 5-acyloxypyrazoles are obtained.
are obtained with 2 mol acid chlorides in ethyl ether.
reactions of 1-phenyl-3-methylpyrazole-5-one with carbonyl compounds
also gave 4-substituted pyrazolone derivatives.
Herein, we report the first microwave enhanced acylation of 1-phenyl-
-methylpyrazole-5-one with acid chlorides under solventless conditions.
[
10,11]
whereas in the absence of the
The 4-acyl-5-acyloxypyrazoles
[
11]
[
11]
The solid state
[
12]
3
The mixture of 1-phenyl-3-methylpyrazole-5-one and acid chlorides in
absence of solvent was irradiated for 8 min in an unmodified household
microwave oven, the contents were cooled to room temperature and
aqueous sodium hydroxide was added to decompose the unreacted acid
chloride. The product precipitated from the solution. The solid material
was filtered and recrystalized with ethanol or ethanol aqueous. Their m.p.,
1
13
IR, H NMR and C NMR indicated that they were 5-acyloxypyrazoles
derivatives rather than 4-acylderivatives. The results for a variety of
substrates are summarized in Scheme 1 and Table 1.
Optimal conditions for the synthesis were found to be 8 min reaction
time using 324 W of microwave irradiation power. These optimal conditions
Scheme 1.

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1
-PHENYL-3-METHYL-5-ACYLOXYPYRAZOLES
2551
Table 1. General Synthesis of 5-Acyloxypyrazoles Produces via
Scheme 1
Yield
a
(%)
Entry
R
3
3
3
3
3
3
3
3
a
b
c
d
e
f
C
6
H
5
87
79
40
81
86
48
37
68
2-ClC
2-NO
4-ClC H
4-NO
4-CH
4-CH C H
6 4
H
2
C
6
H
4
6
4
2 6
C H
4
3
6 4
OC H
g
h
3
6
4
3,5-(NO
2
)
2
C
H
6 3
a
All yields refer to isolated pure products.
were then applied for the synthesis of the other 5-acyloxypyrazoles. It has
been found that substituted group of acid chloride has effect on the yield.
When p-substituted group is electron-attracting group, the reaction gives
higher yield than the case where substituted group is electron-donating
group. When o-substituted group is nitro group, the yield is lower than
chloro-substituted one, this effect may be interpreted with the steric
hindrance of the substituted group in benzoyl chlorides. Under the same
conditions, acids did not react with 1-phenyl-3-methylpyrazole-5-one.
Meanwhile, the presence of excessive acid chlorides did not affect the
reaction results.
In conclusion, a rapid and practical procedure for the synthesis of
-acyloxypyrazoles from 1-phenyl-3-methylpyrazole-5-one and acid chlor-
5
ides under microwave irradiation was developed, which involves solvent-free
conditions. The operation simplicity, faster reaction rates, and ease of
manipulation render this a useful and attractive route for the synthesis of
5-acyloxypyrazoles.
EXPERIMENTAL
All melting points are uncorrected. Yields refer to isolated products.
The products were characterized by comparison of their spectral (IR,
1
13
H NMR, C NMR and MS).
-Acyloxypyrazoles (3d). A Typical Procedure: A mixture of 1-phenyl-
-methylpyrazole-5-one (6 mmol) and acid chloride (8 mmol) was mixed in a
5
3
beaker covered with a watch glass, was placed in an unmodified household

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552
BAI ET AL.
microwave oven and irradiated for 8 min at the power of 324 W. Then, 40%
aqueous sodium hydroxide was added till the pH of the solution was about 9,
and boiled the solution for a few minutes until the smell of acid chloride
disappeared. After cooling, the solid products were filtered, washed with
cold water, dried and recrystallized from ethanol or ethanol aqueous to
ꢀ
give crystals of the product 3d in 81% yield (1.5 g); m.p. 95–96 C. IR
(
KBr): 1748, 1592, 1548, 1500, 1443, 1392, 1250, 1145, 1065, 1007,
À1
1
45 cm . H NMR (400 MHz, CDCl ): 2.36 (s, 3H, Me), 6.27 (s, 1H, H-
8
4
8
3
), 7.28–7.33 (t, 1H, phenyl), 7.40–7.46 (m, 4H, phenyl), 7.55–7.59 (d, 2H, J
.4 Hz, chlorobenzoyl), 7.96–8.01 (d, 2H, J 8.4 Hz, chlorobenzoyl);
C NMR (400 MHz, CDCl ): 14.45, 95.74, 123.17, 126.38, 127.19, 129.04,
3
1
3
129.19, 131.58, 138.04, 140.90, 144.19, 149.04, 160.96. MS m/z: 312, 277,
173, 139(100), 111, 77, 51.
ACKNOWLEDGMENTS
We thank the science foundation of Northwest University (99NW48)
for financial support.
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(
Received in the UK June 22, 2001

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