Heteropolyacids as green and reusable catalysts for the synthesis of isoxazole derivatives

Article abstract of DOI:10.1080/00397910701651326

Heteropolyanions with different structures, including Keggin, Dawson, Preyssler, mixed addenda, and sandwich types, catalyzed the formation of 1,3-diphenyl-isoxazole from the condensation of 1,3-diphenyl-propane-1,3-dione and hydroxylamine hydrochloride in different solvents and under heating conditions. Our data vividly indicate that H3PW11CuO40 is the catalyst of choice and could catalyze the synthesis of other isoxazole derivatives in high yields and good selectivities. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701651326

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Heteropolyacids as Green and Reusable
Catalysts for the Synthesis of Isoxazole
Derivatives
a
a
a
Majid M. Heravi , Fatemeh Derikvand , Anahita Haeri , Hossein A.
a
b
Oskooie & Fatemeh F. Bamoharram
a
Department of Chemistry, School of Science, Azzahra University, Vanak,
Tehran, Iran
b
Department of Chemistry, Azad University of Mashhad, Mashad, Iran
Published online: 25 Jan 2008.
To cite this article: Majid M. Heravi , Fatemeh Derikvand , Anahita Haeri , Hossein A. Oskooie & Fatemeh
F. Bamoharram (2007): Heteropolyacids as Green and Reusable Catalysts for the Synthesis of Isoxazole
Derivatives, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 38:1, 135-140
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Synthetic Communications , 38: 135–140, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701651326
Heteropolyacids as Green and Reusable
Catalysts for the Synthesis of Isoxazole
Derivatives
1
Majid M. Heravi, Fatemeh Derikvand, Anahita Haeri,
1
1
1
Hossein A. Oskooie, and Fatemeh F. Bamoharram
2
1
Department of Chemistry, School of Science, Azzahra University,
Vanak, Tehran, Iran
Department of Chemistry, Azad University of Mashhad, Mashad, Iran
2
Abstract: Heteropolyanions with different structures, including Keggin, Dawson,
Preyssler, mixed addenda, and sandwich types, catalyzed the formation of 1,3-
diphenyl-isoxazole from the condensation of 1,3-diphenyl-propane-1,3-dione and
hydroxylamine hydrochloride in different solvents and under heating conditions. Our
3
data vividly indicate that H PW11CuO40 is the catalyst of choice and could catalyze
the synthesis of other isoxazole derivatives in high yields and good selectivities.
Keywords: b-dicarbonyl compounds, heteropolyacids, HPAs, hydroxyl amine,
isoxazole derivatives
INTRODUCTION
Heteroaromatic compounds have attracted considerable attention in the design
[1]
of biologically active molecules and advanced organic materials. Hence, a
practical method for the preparation of such compounds is of great interest
in synthetic organic chemistry.
Nitrogen-containing ring systems have been widely used as ligands in
organometallic chemistry, and their role as “tunable” ligands, as well as
[
2,3]
their application as cryptands, cannot be overstated.
of nitrogen-containing heterocycles includes the oxazole ring systems.
An important class
Received in Poland March 28, 2007
Address correspondence to Majid M. Heravi, Department of Chemistry, School of
Science, Azzahra University, Vanak, Tehran, Iran. E-mail: mmh1331@yahoo.com
1
35

1
36
M. M. Heravi et al.
Isoxazole moieties represent a class of unique pharmacophores, which are
[4]
constituent units of diverse therapeutic agents. Therefore, they are interest-
ing targets in the development of new drug leads in solid-phase combinatorial
chemistry. A considerable number of methods to synthesize substituted isoxa-
zoles have been published including approaches based on condensation of 1,3-
[5]
dicarbonyl compounds with hydroxylamine, addition of nitrile oxides to
[
supported alkynes or anchoring a nitrile oxide precursor onto the solid
6]
[
7]
[8]
[9]
phase, intermolecular cycloadditions, condensations, and intramolecu-
[
10]
lar cyclizations of amino acids.
The drive toward clean technologies, which was brought about by public,
legislative, and corporate force, will provide new and exciting opportunities
[
11]
for catalysis and catalytic processes.
chemistry has at its heart the utilization of methods that reduce or eliminate
Chemical clean technology or green
[12,13]
the use or generation of hazardous substances.
This embraces the
principle of clean synthesis, which involves improvements in process
selectivity, high atom efficiency, and easy separation with reuse of nonpro-
duct components. The efficient use of solid catalysts can go a long way to
[
14]
achieving these goals.
Heteropoly compounds have many advantages as
catalysts that make them economically and environmentally attractive both
in academic and industrial chemistry. They are effective catalysts for
[15,16]
various reactions and have high capability in practical uses, because
their redox and acidic activity can be controlled at the atomic/molecular
levels by changing the constituent elements wherever it is needed in the
[
17]
chemical processes.
forms and also in homogeneous and heterogeneous catalysis.
In continuation of our interest on the catalytic activities of heteropolya-
These solid acids are applied in bulk or supported
[18]
[
19–27]
cids,
herein we report that H PW CuO as a Keggin-type heteropo-
3 11 40
lyacid is an excellent and effective catalyst for the synthesis of isoxazole
derivatives in ethanol (Scheme 1).
To choose the most appropriate medium in this heterocyclization reaction,
synthesis of 3,5-diphenyl-isoxazole from the condensation of 1,3-diphenyl-
propane-1,3-dione and hydroxylamine hydrochloride in the presence of a
catalytic amount of H SiW O was selected as a model reaction. We
4
12 40
carried out the model reaction in different solvents. Among the tested
solvents, the best results were obtained in refluxing ethanol (Table 1).
The effect of a variety of heteropolyacids including Keggin, Dawson,
Preyssler, mixed addenda, and sandwich types in the synthesis of 3,5-
diphenyl-isoxazole in refluxing ethanol was also explored. As shown in
Scheme 1.

Heteropolyacids as Green Catalysts
137
Table 1. Effect of the solvent on the synthesis of 3,5-diphenyl-isoxazole using
catalytic amount of H [Na P W O110]
1
4
5
30
Temperature
(8C)
a
Entry
Solvent
CH
Time (min)
Yield (%)
1
2
3
4
5
6
C H
5
3
110
100
118
64
240
240
90
50
50
65
97
99
H O
2
CH COOH
3
MeOH
EtOH
90
45
78
a
Yields were obtained using GC analysis.
Table 2, H PW CuO gave the best results in terms of yields and times. It is
3
11
40
difficult to clarify clearly the different activity between these catalysts.
Obviously there is a complex relationship between the activity and structure
of polyanions and by changing the constituent elements of polyanion (both
hetero and addenda atoms), the acid strength of HPAs is able to vary in a
wide range. It is suggested that the interactions of the polarized polyanion
with substrate is an important factor in catalytic activity in this reaction.
To establish the scope of this novel methodology, we tested a variety of
b-dicarbonyl- compounds under optimized reaction conditions (Table 3).
The reusability of the catalyst was also studied. After completing the
model reaction in refluxing ethanol (entry 1, Table 3), the catalyst was
removed by simple filtration, washed with diethyl ether, and subjected to a
second run of the reaction process with the same substrate. The results of
the first experiment and subsequent ones were almost consistent in yields
after three runs (99%, 97%, 95%).
In summary, we have developed an alternative simple procedure for the
synthesis of isoxazole derivatives using H PW CuO as an ecofriendly, inex-
pensive, and efficient catalyst. High yields, relatively short reaction times,
3
11
40
Table 2. Effect of the catalysts on the synthesis of 3,5-diphenyl-isoxazole
a
Entry
Catalyst
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
H
6
PMo
9
VO40
240
120
90
97
98
80
80
70
98
96
96
95
99
H SiW O
4
4
3
12 40
H
H
SiMo12
PW12
O
40
O
40
100
150
120
120
180
150
45
K Na P W O
7 18 62
3
2
H14NaP5W29MoO110
6 2 18 62
H P W O
H NaP W O
1 30 110
4
5
.
(H O) O62 20H O
K
10
P
2
W
18Co
4 2 2 2
1
0
H
3
PW11CuO40
a
Yields were obtained using GC analysis.

1
38
M. M. Heravi et al.
Table 3. Synthesis of isoxazole derivatives in the presence of a catalytic amount of
H [NaP W O110] under solvent-free conditions at 1308C
1
4
5
30
a
Entry
1
Substrate
Product
Time (min)
45
Yield (%)
99
1,3-Diphenyl-pro
pan1,3-dione
2
3
Acetylacetone
60
45
98
97
1,3-Di(tert-butyl)-
1
,3-propandione
4
5
6
7
8
Benzoylacetone
65
45
97
97
92
90
98
Ethyl benzoyl acetate
Ethylacetoacetate
Methylacetoacetate
140
140
30
2-Acetyl-
cyclohexanone
a
Yields were obtained using GC analysis.
simplicity of operation, and easy workup procedure are some advantages of this
protocol. We believe this methodology can find use in organic synthesis.
EXPERIMENTAL
All compounds were known, and their physical and spectroscopic data were
compared with those of authentic samples and found to be identical. Yields
were obtained using GC analysis.
Synthesis of Isoxazole Derivatives: General Procedure
A mixture of a b-dicarbonyl compound (1 mmol), hydroxylamine hydrochlo-
ride (1 mmol), and a catalytic amount of heteropolyacid (1 mol%) was

Heteropolyacids as Green Catalysts
139
refluxed in ethanol (5 cc) for the indicated time as required to complete the
reaction (Table 3). Upon completion of the reaction, monitored by thin-
layer chromatography (TLC), the mixture was filtered to separate the
insoluble catalyst and then cooled to room temperature. The precipitated
products were separated by filtration.
In the case of liquid products, after separation of catalyst, the solvent was
evaporated. More purification was obtained by column chromatography.
The separated catalyst could be washed with diethyl ether and reused.
Selected Spectroscopic Data
1
,5-Diphenyl-isoxazole (entry 1, Table 3): H NMR (80 MHz, CDCl ) d
3
3
(
ppm): 6.83 (s, 1H), 7.25–7.51 (m, 4H), 7.79–7.94 (m, 6H). IR, y (KBr):
2
1
3
114, 1649, 1619, 1594 cm
,5-Di(t-butyl)-isoxazole (entry 3, Table 3): H NMR (300 MHz, CDCl ) d
.
1
3
ppm): 1.28 (s, 3H), 1.32 (s, 3H), 6.12 (s, 1H). IR, y (KBr): 2971, 1590 cm .
3
21
(
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