Microwave-assisted aromatization of 1,3,5-trisubstituted 2-pyrazolines by Bi(NO3)3 · 5H2O, as a novel and convenient oxidizing agent

Article abstract of DOI:10.1080/00397910500214136

Bismuth(III) nitrate pentahydrate, Bi(NO₃)₃ · 5H₂O, has been used as a mild, efficient, and inexpensive oxidant for the oxidative aromatization of several 1,3,5-trisubstituted 2-pyrazolines to pyrazoles in acetic acid unde

Full text of DOI:10.1080/00397910500214136

This article was downloaded by: [University of California, San Diego]
On: 13 September 2014, At: 13:14
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Microwave‐Assisted
Aromatization of
1
2
,3,5‐Trisubstituted
‐Pyrazolines by
Bi(NO ) ꢀ·ꢀ5H O, as a Novel and
3
3
2
Convenient Oxidizing Agent
a
a
Davood Azarifar & Behrooz Maleki
a
Department of Chemistry, School of Science ,
Bu‐Ali Sina University , Hamadan, Iran
Published online: 18 Aug 2006.
To cite this article: Davood Azarifar & Behrooz Maleki (2005) Microwave‐Assisted
Aromatization of 1,3,5‐Trisubstituted 2‐Pyrazolines by Bi(NO ) ꢀ·ꢀ5H O, as a Novel and
3
3
2
Convenient Oxidizing Agent, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 35:19, 2581-2585
To link to this article: http://dx.doi.org/10.1080/00397910500214136
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views

expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

w
Synthetic Communications , 35: 2581–2585, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500214136
Microwave-Assisted Aromatization of
1
Bi(NO ) 5H O, as a Novel and Convenient
,3,5-Trisubstituted 2-Pyrazolines by
.
3
3
2
Oxidizing Agent
Davood Azarifar and Behrooz Maleki
Department of Chemistry, School of Science, Bu-Ali Sina University,
Hamadan, Iran
.
3 3 2
Abstract: Bismuth(III) nitrate pentahydrate, Bi(NO ) 5H O, has been used as a mild,
efficient, and inexpensive oxidant for the oxidative aromatization of several 1,3,5-
trisubstituted 2-pyrazolines to pyrazoles in acetic acid under microwave irradiation
with good to excellent yields.
.
Keywords: Aromatization, Bi(NO3)3 5H O, bismuth(III) nitrate pentahydrate,
microwave irradiation, 1,3,5-trisubstituted pyrazolines
2
During the past few decades, a considerable portion of research publications
and reviews have been allocated to the application of microwave technology
[
1]
in organic synthesis. Microwave irradiation has received much attention
because it requires short reaction times and provides simplicity in handling,
enhanced reaction yields, and high-purity products. Furthermore, the
oxidative aromatization of 1,3,5-trisubstituted 2-pyrazolines to pyrazoles is
of great biological importance because of their analgesic, antiinflammatory,
antipyretic, antiarrhythmic, muscle relaxant, psychoanaleptic, antidiabetic,
Received in Poland May 5, 2005
Address correspondence to Davood Azarifar, Department of Chemistry, School of
Science, Bu-Ali Sina University, Postal Code 65174, Hamadan, Iran. Fax: þ98(811)
8
272404; E-mail: azarifar@basu.ac.ir
2
581

2582
D. Azarifar and B. Maleki
[
2,3]
and antibacterial activities.
We have previously reported on the convenient
preparation of 2-pyrazolines from reactions between hydrazines and chalcone
intermediates, which can be generated from reactions of aromatic ketones with
[
4–6]
aldehyeds.
matization by suitable oxidants should provide a convenient approach to
In view of the simple preparation of 2-pyrazolines, their aro-
[7]
pyrazoles. In this regard, a variety of oxidizing agents such as Zr(NO ) ,
3
4
[8]
[9]
[10]
[11]
Pd/C, Co(II) and oxygen, MnO2,
tetraacetate
iodobenzene diacetate,
have been reported. However, most of these reagents present
and lead
[12]
several disadvantages including long reaction times, unavailability of the
reagents, toxicity because of the presence of certain toxic elements in these
reagents, hard workup, and unsatisfactory yields of the products. Thus, in
view of these drawbacks, there is a need to search for new high-yielding,
environmentally safe, and cheaply available reagents for conversion of 2-pyr-
azolines to pyrazoles. In continuation of our ongoing research on oxidation
[
13–19]
of 1,3,5-trisubstituted 2-pyrazolines,
oxidative aromatization of 1,3,5-trisubstituted 2-pyrazolines to their corre-
herein we report an efficient
.
sponding pyrazoles using crystalline Bi(NO3)3 5H O under microwave
2
irradiation (Scheme 1).
Because of the versatility of Bi(NO ) 5H O as a useful reagent in
.
3
3
2
[
20–23]
organic synthesis,
2
we examined the aromatization of 1,3,5-trisubstituted
-pyrazolines (1a–o) to their corresponding pyrazoles (2a–o) under
microwave irradiation using this reagent and found it to be an effective
oxidant with high yields of products (92–99%) and very short reaction
times (35–60 s) (Tables 1 and 2).
EXPERIMENTAL
All melting points were determined on a B u¨ chi 530 melting-point apparatus
and are uncorrected. IR spectra were recorded using a Shimadzu 435-U-04
1
13
spectrophotometer (KBr pellets). H NMR and C NMR spectra were
obtained using a 90-MHz JEOL FT NMR spectrometer. The CHN analysis
was carried out in Iranian Petroleum Research Center (Ray City, Tehran,
Iran).
Scheme 1.

Aromatization of 1,3,5-Trisubstituted 2-Pyrazolines
2583
Table 1. Substrates (1a–o) and their corresponding products (2a–o)
1
R
2
R
Substrate
Product
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
a
b
c
d
e
f
2a
2b
2c
2d
2e
2f
2-Naphthyl
Ph
o-CH C H
3 6 4
Ph
m-CH
o-CH C H
3 6 4
p-CH
C
3 6
H
4
3 6 4
C H
p-CH OC H
3
6
4
4
4
4
p-CH OC H
m-CH C H
6
3
3
3
6
6
6
3
4
p-CH
p-CH
OC
OC
H
H
Ph
p-ClC
g
h
i
2g
2h
2i
6
H
4
2-Naphthyl
2-Naphthyl
2-Naphthyl
p-CH OC H
m-CH C H
3
6
6
6
4
p-ClC
o-ClC
H
4
4
4
j
2j
H
k
l
2k
2l
o-ClC H
6
3
6
4
Ph
Ph
Ph
Ph
p-CH
p-NO
m-ClC H
3
OC
6
H
4
m
n
o
2m
2n
2o
2 6 4
C H
6
4
6 4
p-BrC H
Table 2. Microwave-assisted aromatization of 1,3,5-trisubstituted 2-pyrazolines by
.
Bi(NO3)3 5H O
2
Melting point (8C)
Found Literature
a
b
c
Substrate
Product
Time (s)
Yield (%)
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
a
b
c
d
e
f
2a
2b
2c
2d
2e
2f
40
35
55
50
60
45
40
60
50
45
45
50
50
55
55
99
98
96
98
95
99
97
99
94
96
94
98
94
92
95
148–150
139–141
100–102
73–76
151–152
136–138
95–98
70–72
84–86
75–77
101–103
75–78
130–133
72–75
63–65
77–78
143
82–84
77–79
g
h
i
2g
2h
2i
102–104
79–81
127–130
70–72
66–69
j
2j
k
l
2k
2l
75–77
m
n
o
2m
2n
2o
139–141
93–95
126–128
91
131
a
All the isolated products were characterized on the basis of their physical properties
1
13
and H NMR, C NMR, and IR spectra and by direct comparison with authentic
compounds.
b
Isolated yields.
Literature data, 2a–k,
c
[17]
[11]
[10]
and 2n–o.
2l–m,

2584
D. Azarifar and B. Maleki
Oxidation of 1,3,5-Trisubstituted 2-Pyrazolines
.
with Bi(NO3)3 5H O: General Procedure
2
.
Crystalline Bi(NO3)3 5H O (1.2 mmol) was added to a flask containing 1,3,5-
2
trisubstituted 2-pyrazolines (1a–o) (2 mmol) dissolved in glacial AcOH
(10 ml). The resulting mixture was then placed in an alumina bath inside a
microwave oven (900 W) and irradiated for 30–60 s. After complete conver-
sion of the substrate as monitored by TLC using a mixture of ethyl acetate and
n-hexane (1 : 9), the mixture was quenched with NaHCO solution (5%) and
3
extracted with CH Cl (2 ꢀ 10 ml). Then, the organic layer was dried over
2
2
anhydrous MgSO and evaporated to leave an oily residue, which, upon crys-
4
tallization from aqueous EtOH (96%), gave yellow crystalline products
(2a–o) in 92–99% yield (Table 1).
REFERENCES
1
2
3
. Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.; Jacquault, P.; Mathe, D. New
solvent-free organic synthesis using focused microwawes. Synthesis 1998,
1213–1234.
. Parmar, S. S.; Pandey, B. R.; Dwivedic, C.; Harbison, R. D. Anticonvulsant
activity and mono amine oxidase inhibitory properties of 1,3,5-trisubstituted pyra-
zolines. J. Pharm. Sci. 1974, 63, 1152.
. Takabatake, E.; Kodama, R.; Tanaka, Y.; Dohmori, R.; Tachizawa, H.; Naito, T.
Metabolic fate of 1-(4-methoxy-6-methyl-2-pyrimidinyl)-3-methyl-5-methoxy
pyrazole (mepirizole, DA-398) in rats and rabbits. Chem. Pharm. Bull. 1970, 18,
1900.
4
. Azarifar, D.; Shaebanzadeh, M. Synthesis and characterization of new 3,5-
dinaphthyl-substituted 2-pyrazolines and study of their antimicrobal activity.
Moleclues 2002, 7, 885–889.
5
6
. Azarifar, D.; Ghasemnejad, H. Microwave-assisted synthesis of some 3,5-arylated
2
-pyrazolines. Moleclues 2003, 8, 642–648.
. Azarifar, D.; Maleki, B. Silica-supported synthesis of some 1,3,5-trisubstituted
-Pyrazolines under solvent-free and microwave irradiation conditions.
2
J. Heterocycl. Chem. 2005, 157.
. Sabitha, G.; Kumar Reddy, G. S. K.; Reddy, Ch. S.; Fatima, N.; Yadav, J. S.
Zr(NO ) : A versatile oxidizing agent for aromatization of hantzsch 1,4-Dihydro-
3 4
pyridines and 1,3,5-trisubstituted pyrazolines. Synthesis 2003, 1267–1271.
. Nakamichi, N.; Kawashita, Y.; Hayashi, M. Oxidative aromatization of 1,3,5-tri-
substituted pyrazolines and hantzsch 1,4-dihydropyridines by Pd/C in acetic
acid. Org. Lett. 2002, 4, 3955.
. Shah, J. N.; Shah, C. K. Oxidative dehydrogenation of pyrazolines with cobalt(II)
And oxygen. J. Org. Chem. 1978, 43, 1266.
7
8
9
1
0. Bhatnage, I.; George, M. V. Oxidation with metal oxides—II. Oxidation of
chalcone phenylhydrazones, pyrazolines, o-aminobenzylidine anils, o-hydroxy
benzylidine anils with manganese dioxide. Tetrahedron 1967, 24, 1293–1298.
1. Singh, S. P.; Kumar, D.; Prakash, O.; Kapoor, R. P. Hypervalent iodine oxidation
of 1,3,5-trisubstituted pyrazolines: A facile synthesis of 1,3,5-trisubstituted pyra-
zolines. Synth. Commun. 1997, 27, 2683–2689.
1

Aromatization of 1,3,5-Trisubstituted 2-Pyrazolines
2585
1
1
2. Gladston, W. A.; Norman, O. C. Reaction of lead tetracetate. Part VII. Some
Reactions leading to pyrazoles. J. Chem. Soc. Chem. Commun. 1966, 1536.
3. Azarifar, D.; Zolfigol, M. A.; Maleki, B. 1,3-Dibromo-5,5-dimethylhydantoin as a
novel oxidizing agent for the oxidation of 1,2,3-trisubstituted pyrazolines under
both heterogeneous and solvent-free conditions. Bull. Korean Chem. Soc. 2004,
25, 23.
1
1
1
4. Zolfigol, M. A.; Azarifar, D.; Maleki, B. Trichloroisocyanuric acid as a novel
Oxidizing agent for the oxidation of 1,3,5-trisubstituted pyrazolines under both
Heterogeneous and solvent-free conditions. Tetrahedron Lett. 2004, 45, 2181.
5. Ghorbani-Vaghei, R.; Azarifar, D. B.; Maleki, B. N, N -dibromo-N,N -1,2-
ethanediylbis (P-toluenesulphonamide) as a useful reagent for oxidation of
0
0
1
,3,5-trisubstituted pyrazolines. Bull. Korean Chem. Soc. 2004, 25, 953.
0
0
6. Ghorbani-Vaghei, R.; Azarifar, D.; Khazaei, A.; Maleki, B. N,N ,N,N -tetrabromo-
benzene-1,3-disulfonylamide as a novel reagent for oxidative Aromatization of
1,3,5-trisubstituted 2-pyrazolines under heterogeneous and solvent-free con-
ditions. Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 1877–1881.
7. Azarifar, D.; Zolfigol, M. A.; Maleki, B. Silica-supported 1,3-dibromo-5,5-
dimethylhydantoin (DBH) as a useful reagent for microwave-assisted aromatization
of 1,3,5-trisubstituted 2-pyrazolines under solvent-free conditions. Synthesis
1
2004, 11, 1744.
1
1
2
2
2
2
8. Ghorbani-Vaghei, R.; Azarifar, D.; Maleki, B. Mild oxidation of 1,3,5-trisubsti-
tuted pyrazolines with N-bromo-sulphonamides. J. Chin. Chem. Soc. 2004, 51,
1
373.
9. Azarifar, D.; Maleki, B. Micriowave-assisted aromatization of 1,3,5-trisubstituted
- pyrazolines by silica-supported N-bromosuccinimide as a useful reagent under
2
solvent-free ‘dry’ conditions. Heterocycles 2005, 65, 865–870.
0. Mohammadpoor-Baltork, I.; Khosropour, A. R.; Aliyan, H. Efficient conversion of
epoxides to 1,3-dioxolanes catalyzed by bismuth(III) salts. Synth. Commun. 2001,
31, 3411–3416.
1. Firouzabadi, H.; Mohammadpoor-Baltork, I.; Kolagar, S. Arapid, selective, and
efficient method for deprotection of silyl ethers catalyzed by bismuth(III) salts.
Synth. Commun. 2001, 31, 905–909.
2. Mashraqui, S. H.; Karnik, M. A. Bismuth nitrate pentahydrate: A convenient
reagent for the oxidation of hantzch 1,4-dihydropyridines. Synthesis 1998,
713–714.
3. Mohammadpoor-Baltork, I.; Khosropour, A. R. Bismuth(III) salts as new Catalyst
for the selective conversion of trimethylsilyl and tetrahydropyranyl ethers to their
corresponding acetates and formats. Synth. Commun. 2002, 32, 2433–2439.