Tricholoroisocyanuric acid as a useful reagent in microwave-assisted aromatization of 1,3,5-trisubstituted 2-pyrazolines

Article abstract of DOI:10.1002/jccs.200500174

An efficient aromatization of 1,3,5-trisubstituted 2-pyrazolines to their corresponding pyrazoles has been performed by tricholoroisocyanuric acid [TCCA] under microwave irradiation in excellent yields. It has been observed that the reactions occur more r

Full text of DOI:10.1002/jccs.200500174

Journal of the Chinese Chemical Society, 2005, 52, 1215-1217
1215
Tricholoroisocyanuric Acid as a Useful Reagent in Microwave-assisted
Aromatization of 1,3,5-Trisubstituted 2-Pyrazolines
Davood Azarifar* and Behrooz Maleki
Department of Chemistry, School of Science, Bu-Ali Sina University, Postal code 65174, Hamadan, Iran
An efficient aromatization of 1,3,5-trisubstituted 2-pyrazolines to their corresponding pyrazoles has been
performed by tricholoroisocyanuric acid [TCCA] under microwave irradiation in excellent yields. It has been
observed that the reactions occur more rapidly under microwave irradiation conditions, and the amount of the
reagent TCCA consumed is considerably reduced to afford better yields when compared with conventional
thermal conditions at the same temperature.
Keywords: 2-Pyrazolines; Pyrazoles; Oxidation; Aromatization; Microwave irradiation;
Tricholoroisocyanuric acid; [TCCA].
INTRODUCTION
The use of microwave irradiation as a non-conventional
our previously reported protocols on the oxidative aromatiza-
tion of pyrazolines,12 we report herein on a facile micro-
wave-accelerated oxidation of 2-pyrazolines to pyrazoles by
tricholoroisocyanuric acid [TCCA] under microwave irradi-
ation. Our objective in this work focused on some interesting
features such as (a) the rapid reaction rates (b) higher yields
of products and cleaner reaction conditions and (c) the low
consumption of the oxidant.
energy source has become of considerable interest in organic
chemistry. The frequency of publications and reviews during
the last few decades has substantiated the advantages and ver-
satility of microwave irradiation in easy and high yielding
oxidation of organic compounds. This novel method is there-
fore a fast growing and clean practice in organic synthesis
which has several advantages over classical thermal condi-
tions in providing increased reaction rates, simplicity and im-
proved yields.1 The oxidative aromatization of 1,3,5-trisub-
stituted 2-pyrazolines to pyrazoles is biologically important,
since many pyrazole derivatives possess analgesic, anti-in-
flammatory, antipyretic, antiarrhythmic, muscle relaxant,
psychoanaleptic, antidiabetic and antibacterial activities.2
1,3,5-Trisubstituted 2-pyrazolines can be conveniently pre-
pared from hydrazines and chalcone intermediates.3 There-
fore, oxidative aromatization of 2-pyrazolines by oxidizing
agents should provide an efficient method for the prepara-
tion of pyrazole derivatives. A variety of oxidants such as
Zr(NO3)4,4 Pd/C,5 carbon-promoted oxygen,6 Co(II) and oxy-
gen,7 iodobenzene diacetate,8 lead tetraacetate,9 MnO2,10 and
KMnO4,11 have been previously reported; most suffer from
the use of excess reagent, longer reaction times, higher tem-
peratures, acidic media, formation of side products and toxic-
ity due to the presence of toxic transition metal cations like
Co(II), Pb(IV), Hg(II), Mn(IV and VII), Ag(I), Zr(IV) within
the structural formula of the reagents employed. Following
The reaction of 1,3,5-trisubstituted 2-pyrazolines with
TCCA under microwave irradiation afforded pyrazoles with
no side products (Scheme I).
Scheme I
O
R1
R1
R2
R2
Cl
O
Cl
O
N
N
AcOH
+
Microwave
N
N
N
N
N
Ph
Ph
Cl
[1a-p]
[2a-p]
The results obtained from the conversion of various
1,3,5-trisubstituted 2-pyrazolines 1a-p into their correspond-
ing pyrazoles 2a-p are summarized in Tables 1 and 2.
EXPERIMENTAL
All the melting points were determined on a Büchi 530
melting point apparatus and reported uncorrected. IR spectra
* Corresponding author. Fax: +98-811-8272404; E-mail: azarifar@basu.ac.ir

1216 J. Chin. Chem. Soc., Vol. 52, No. 6, 2005
Azarifar and Maleki
Table 1. Substrates 1a-p and their corresponding products 2a-p
Procedure for oxidation of 1,3,5-trisubstituted
R1
R2
2-pyrazolines by TCCA
Substrate
Product
To a stirred solution of acetic acid (5 mL) was added the
substrate 1a-p (1 mmol) and TCCA in appropriate amounts
(Table 2). The resulting mixture was then placed in an alu-
mina bath inside an MW oven (900 W) and irradiated for 3-5
min. After the complete conversion of the substrate as moni-
tored by TLC, the solvent was evaporated under reduced
pressure and the products were extracted with dicholoro-
methane. The solid residue was purified by flash chromatog-
raphy (using n-hexane/ethyl acetate 10:1) to give the corre-
sponding pyrazoles 2a-p (Table 2).
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2-Naphthyl
Ph
o-CH3C6H4
Ph
m-CH3C6H4
o-CH3C6H4
m-CH3C6H4
Ph
p-ClC6H4
m-CH3C6H4
p-ClC6H4
o-ClC6H4
p-(CH3)2NC6H4
o-ClC6H4
Ph
p-(CH3)2NC6H4
p-BrC6H4
m-ClC6H4
p-CH3C6H4
p-CH3OC6H4
p-CH3OC6H4
p-CH3OC6H4
p-CH3OC6H4
2-Naphthyl
2-Naphthyl
2-Naphthyl
m-CH3C6H4
p-CH3OC6H4
2-Naphthyl
o-CH3C6H4
Ph
Received April 25, 2005.
Ph
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78
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90
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74
80
96
94
96
96
94
92
92
94
96
92
92
96
94
96
90
90
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