Silica sulfuric acid-activated poly-1,3-dichloro-5methyl-5-(4'-vinylphenyl)hydantoin (PDCVH) as an effective reagent for oxidation of 1,3,5-trisubstituted 2-pyrazolines both under microwave irradiation and thermal conditions

Article abstract of DOI:10.3987/COM-07-11248

Oxidation of 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazoles to the corresponding pyrazoles has been achieved by utilizing silica sulfuric acidactivated poly-1,3-dichloro-5-methyl-5(4'-vinylphenyl)hydantoin in EtOH under both microwave irradiation and conve

Full text of DOI:10.3987/COM-07-11248

HETEROCYCLES, Vol. 75, No. 3, 2008
669
HETEROCYCLES, Vol. 75, No. 3, 2008, pp. 669 - 673. © The Japan Institute of Heterocyclic Chemistry
Received, 21st October, 2007, Accepted, 3rd December, 2007, Published online, 7th December, 2007. COM-07-11248
SILICA SULFURIC ACID-ACTIVATED POLY-1,3-DICHLORO-5-
METHYL-5-(4’-VINYLPHENYL)HYDANTOIN
(PDCVH)
AS
AN
EFFECTIVE REAGENT FOR OXIDATION OF 1,3,5-TRISUBSTITUTED
2-PYRAZOLINES BOTH UNDER MICROWAVE IRRADIATION AND
THERMAL CONDITIONS
Davood Azarifar,* Behrooz Maleki, and Mehrnaz Setayeshnazar
Faculty of Chemistry, Bu-Ali Sina University, Zip Code 65178, Hamedan, Iran
*Corresponding author; Fax: +98(811)8257407; E-mail: azarifar@basu.ac.ir
Abstract – Oxidation of 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazoles to the
corresponding pyrazoles has been achieved by utilizing silica sulfuric acid-
activated poly-1,3-dichloro-5-methyl-5(4’-vinylphenyl)hydantoin in EtOH under
both microwave irradiation and conventional thermal conditions at room
temperature with good yields.
Pyrazole derivatives, amongst five-membered heterocycles, are interesting heterocyclic compounds since
they show a wide range of pharmacological properties including anti-inflammatory,1 anti-cancer,2
anti-bacterial,3 anti-viral,4 anti-diabetic,5 anti-microbial, and anti-fungal activities.6 Some pyrazoles
display agrochemical properties (i.e., herbicidal and soil fungicidal activity) and have applications as
pesticides and insecticides.7 1,3,5-Trisubstituted pyrazoles can be easily obtained by oxidation of their
corresponding pyrazolines produced by cyclization of chalcones with arylhydrazines.8 There is an
obvious demand for oxidation of pyrazolines to pyrazoles due to their importance both as
pharmacological targets and synthetic intermediates. A number of methods have been previously reported
on the oxidation of pyrazolines using a variety of oxidants including Zr(NO3)4,9 carbon-activated
oxygen,10 Pd/C/AcOH,11 Co(II)/O2,12 iodobenzene diacetate,13 Pb(OAc)4,14 MnO2,15 KMnO4,16
Ag(NO3)2,17 HgO,18 N-hydroxyphthalimide (NHPI) 19 and I2O5/KBr.20 However, many suffer from certain
drawbacks such as the use of expensive reagents, longer reaction times, low yields of products and
toxicity of certain elements embodied in these reagents. These limitations necessitate further demand for
new environmentally benign and easily accessible reagents for conversion of 2-pyrazolines to pyrazoles.
In this article, as part of our ongoing efforts to develop more robust methods for oxidative aromatization
of various heterocycles including pyrazolines,21 we describe the use of silica-sulfuric acid-activated

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HETEROCYCLES, Vol. 75, No. 3, 2008
poly-1,3-dichloro-5-methyl-5(4’-vinylphenyl)hydantoin (PDCVH) as a new and efficient system for
aromatization of 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazoles, under microwave irradiation.
In this approach, we have observed that the coupling of microwave irradiation with the use of PDCVH,22
activated by silica sulfuric acid, provides smooth conversion of 2-pyrazolines (1a-m) to 2-pyrazoles
(2a-m) in EtOH with special attributes such as enhanced reaction rates, higher yields of products and
improved ease of manipulation (Scheme 1). The reactions were conducted under microwave irradiation as
well as conventional thermal heating. The results (summarized in Table 1) display the superiority of
microwave irradiation to thermal heating in providing enhanced reaction rates and improved yields.
n
n
R1
R2
R1
R2
O
O
SiO2-OSO3H / EtOH
MW or rt
+
+
N
N
N
N
N
N
N
N
H
H
Cl
Cl
Ph
Ph
2a-m
O
O
1a-m
Scheme 1
It is interesting to know that, the reagent PDCVH can only affect the conversion of pyrazolines to
pyrazoles if a suitable promoter is used in the reaction either under microwave irradiation or thermal
conditions. Several acids including AcOH, TsOH and silica-sulfuric acid have been examined to activate
the reagent to release Cl+ cation. It is noticed that, silica-sulfuric acid appears as the most effective
activator providing highest yields and least reaction times. In addition, when the reactions are allowed to
run in the absence of PDCVH with using solely silica-sulfuric acid in the reaction mixture, no oxidation
of pyrazolines is resulted. This evidence substantiates the role of PDCVH as the main species acting as
oxidant, and any involvement of silica sulfuric acid as the oxidant is ruled out. According to the
experimental results shown in Table 1, more efficient conversion of 2-pyrazolines occurs under
microwave irradiation in EtOH to yield the corresponding pyrazoles in shorter reaction times and higher
yields (78-98%) when compared with the yields obtained under thermal conditions at room temperature
(68-90%). The actual role of PDCVH is not clear at this time. However, a plausible explanation is that
PDCVH might act as a source for Cl+, which in turn activates silica sulfuric acid for further reaction with
pyrazolines.
In conclusion, we have developed a new and mild procedure for oxidation of 2-pyrazolines to 2-pyrazoles
utilizing poly-1,3-dichloro-5-methyl-5(4’-vinylphenyl)hydantoin (PDCVH) as a cheap, non-toxic and
easily recoverable reagent which operates both under microwave irradiation and conventional thermal
conditions at rt.

HETEROCYCLES, Vol. 75, No. 3, 2008
671
Table 1 Oxidative aromatization of 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazoles (1 mmole) (1a-j) with silica sulfuric
acid-activated poly-1,3-dichloro-5-methyl-5(4’-vinylphenyl)hydantoin (PDCVH) in EtOH under both microwave
irradiation and thermal conditions at rt.a
Mp (°C)
Substrate
Productb
R1
R2
Time (min)
Yield (%)c
Found
140-141
79-81
139-142
114-115
80-82
131-133
72-74
152-154
127-129
92-94
70-72
100-102
92-94
Reported9,21
139-140
78-80
142-143
114-115
77-79
130-133
67-70
1a
1b
1c
1d
1e
1f
1g
1h
1i
2a
2b
2c
2d
2e
2f
2g
2h
2i
Ph
Ph
Ph
60 (1.5)
60 (1)
150 (2)
120 (2)
60 (1)
180 (2)
165 (2)
60 (1)
82 (82)
70 (88)
84 (90)
78 (92)
86 (98)
72 (86)
70 (80)
82 (85)
72 (85)
68 (82)
85 (96)
68 (78)
86 (96)
4-MeOC6H4
4-NO2C6H4
4-ClC6H4
Ph
Ph
Ph
4-MeOC6H4
2-naphthyl
2-naphthyl
2-naphthyl
Ph
4-ClC6H4
2-ClC6H4
2-MeC6H4
4-BrC6H4
3-ClC6H4
2-ClC6H4
3-MeC6H4
2-Furyl
148-150
126-128
93-95
150 (1.5)
120 (2)
150 (2)
120 (2)
1j
2j
Ph
1k
1l
2k
2l
4-MeOC6H4
4-MeC6H4
4-MeC6H4
66-68
95-98
1m
2m
150 (2)
93-95
a
b
The reaction data obtained under microwave irradiation are given in parentheses. All the isolated products were characterized on the basis of their
c
physical properties and IR, 1H NMR and 13C NMR spectral analysis and by direct comparison with authentic materials. Isolated yields.
EXPERIMENTAL
IR spectra were recorded using a Shimadzu 435-U-04 spectrophotometer (KBr pellets) and NMR spectra
were obtained using 90 MHz JEOL FT NMR spectrometer. Microwave-assisted reactions were
conducted in a commercial Black & Decker model MX30PG1000 watt microwave oven.
4,5-Dihydro-1H-pyrazoles were all prepared according to our previously reported procedure.8
Poly-1,3-dichloro-5-methyl-5(4’-vinylphenyl)hydantoin was provided by Halosource Company in USA.
1
13
2-Pyrazoles were characterized on the basis of their melting points and IR, H NMR, and C NMR
spectral analysis and compared with the reported data.9,21
Aromatization of 1,3,5-trisubstituted pyrazolines with silica sulfuric acid-activated PDCVH;
General Procedure:
Poly-1,3-dichloro-5-methyl-5(4’-vinylphenyl)hydantoin (0.45g) and silica-sulfuric acid (0.45g) were
added to a flask containing 1,3,5-trisubstituted 2-pyrazolines (1a-m) (1mmol) dissolved in EtOH (5 mL).
The reaction mixture was stirred at rt for the time given in table 1. After the complete conversion of the
substrate as indicated by TLC analysis, the reaction mixture was quenched with aqueous NaHCO3
solution (5%) and extracted with Et2O (10 mL). Then organic layer was dried over anhydrous Na2SO4 and
concentrated to leave the crude products (2a-m) which were purified by recrystallization from EtOH
(96%). In a separate set of experiments, these reactions were all repeated under microwave irradiation
condition in an alumina bath using a MX30PG1000 watt microwave oven.
ACKNOWLEDGEMENT
This project was financially supported by the Research Council of Bu-Ali Sina University (Hamedan,

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HETEROCYCLES, Vol. 75, No. 3, 2008
Iran). We wish to thank the Vanson Halosource Company in USA for generous dedication of PDCVH
reagent.
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