Wells-Dawson type heteropolyacid catalyzed synthesis of quinoxaline derivatives at room temperature

Article abstract of DOI:10.1007/s00706-007-0594-5

Wells-Dawson heteropolyacid (H₆P₂W₁₈O ₆₂ ? 24H₂O) was used as an effective catalyst for the synthesis of biologically active quinoxaline derivatives from the condensation of o-phenylenediamines with 1,2-dicarbonyl compounds at room temperature in excellent yields. Springer-Verlag 2007.

Full text of DOI:10.1007/s00706-007-0594-5

Monatshefte fu¨r Chemie 138, 465–467 (2007)
DOI 10.1007/s00706-007-0594-5
Printed in The Netherlands
Wells-Dawson Type Heteropolyacid Catalyzed Synthesis of Quinoxaline
Derivatives at Room Temperature
Majid M. Heravi1;Ã, Khadijeh Bakhtiari1, Fatemeh F. Bamoharram2, and Maryam H. Tehrani1
1
Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran
2
Department of Chemistry, Azad University of Mashhad, Mashhad, Iran
Received January 13, 2007; accepted (revised) January 18, 2007; published online March 16, 2007
# Springer-Verlag 2007
Summary. Wells-Dawson heteropolyacid (H6P2W18O62
Á
[11–14]. Their synthesis on solid phase has also
been reported [15]. By far the most common method
relies on the condensation of an aryl 1,2-diamine
with a 1,2-dicarbonyl compound in refluxing ethanol
or acetic acid for 2–12 h giving 34–85% yields [16].
The problems associated with the handling and
disposal of inorganic acids, and their environmental
and potential hazards have raised our interest in the
development of alternative procedures using solid
acid catalysts [17, 18]. Due to their super-acidic
properties, heteropolyacids, HPAs, can be used in
reactions requiring electrophilic catalysis. HPAs are
applied both in bulk or supported form, with homo-
geneous and heterogeneous catalysis being possible.
The structure of the Wells-Dawson heteropolyacid
(H6P2W18O62 Á 24H2O) consists of a close-packed
framework of WO6 octahedra surrounding a central
P atom, two identical ‘half units’ PW9 are linked
through the oxygen atoms [19].
As a part of a research project to develop envi-
ronmentally friendly organic reactions [20, 21], we
have recently applied a variety of heteropolyacid
catalysts to different reactions, such as Biginelli re-
action [22], synthesis of 1,1-diacetates [23], and
others [24, 25].
Very recently, we have reported the synthesis of
quinoxaline derivatives catalyzed by CuSO4 Á 5H2O
[26], IBX [27] and Zn[(L)-proline] [28]. In this arti-
cle, we wish to report the catalytic activity of the
Wells-Dawson heteropolyacid H6P2W18O62 Á 24H2O
24H2O) was used as an effective catalyst for the synthesis
of biologically active quinoxaline derivatives from the con-
densation of o-phenylenediamines with 1,2-dicarbonyl com-
pounds at room temperature in excellent yields.
Keywords. Quinoxalines; 1,2-Diketones; o-Phenylenedi-
amines; Heteropolyacid H6P2W18O62 Á 24H2O; Wells-Dawson.
Introduction
In the past ten years, the average number of pub-
lications including the keywords ‘synthesis’ and
‘quinoxaline’ has doubled. A large part of these
papers concerns highly functionalized molecules with
a quinoxaline skeleton designed for biological activ-
ities. Quinoxaline derivatives are an important class
of nitrogen-containing heterocycles and have shown
a broad spectrum of biological activities, such as
antibacterial and anti-inflammatory activities [1, 2].
They have been reported for their applications in
dyes [3], pharmaceuticals [4, 5], and have also
been used as building blocks for the synthesis of
organic semiconductors [6, 7]. Quinoxaline ring
is part of various antibiotics such as Echinomycin,
Levomycin, and Actinoleutin [8, 9] that are known
to inhibit growth of Gram positive bacteria, and are
active against various transplantable tumors [10].
A number of synthesis strategies has been devel-
oped for the preparation of substituted quinoxalines
Ã
Corresponding author. E-mail: mmh1331@yahoo.com

466
M. M. Heravi et al.
Scheme 1
Table 2. Reuse of the catalyst for synthesis of 2,3-diphenyl-
quinoxaline 3a
in a sustainable, simple preparation of functionalized
quinoxalines at room temperature in excellent yields
(Scheme 1).
Run
1
2
3
4
5
Yield=%a
99
97
94
92
89
Results and Discussion
a
Yields were analyzed by GC
The synthesis strategy involves the preparation of
quinoxalines 3 from diamines 1 and 1,2-dicarbonyl
compounds 2 using H6P2W18O62 Á 24H2O as the cat-
alyst. The reaction proceeds very cleanly at room
temperature and no undesirable side reactions were
observed. In the absence of the catalyst, the reaction
did not complete, even after 24 h. The results are
shown in Table 1.
The optimum yield of the product 3 was obtained
when 1 mol% of HPA was used. Among the solvents
tested for this reaction CHCl3, CH3CN, H2O, and
AcOH, the latter was found to be the most efficient
with respect to short reaction times and maximum
yield of the products.
o-Phenylenediamines and 1,2-dicarbonyl compounds
which have electron-donating or electron-withdraw-
ing groups were used and, as expected, in all cases
quinoxalines were obtained in good yields.
It is noteworthy to mention that the catalyst is re-
cyclable and could be reused without significant loss
of activity. Even after five runs the catalytic activity
of H6P2W18O62 Á 24H2O was almost the same as
that of the freshly used catalyst (see Table 2).
In conclusion, we developed the use of the Wells-
Dawson heteropolyacid H6P2W18O62 Á 24H2O as an
inexpensive, reusable, easy to handle, non-corrosive,
and environmentally benign catalyst for the synthe-
sis of biologically active quinoxalines from aromatic
o-diamines and 1,2-dicarbonyl compounds. The ad-
vantages of the present procedure are simplicity of
operation, the high yields of products, and the re-
cyclability of the catalyst. In this reaction the cata-
lyst can be recovered by filtration and washing with
n-hexane, and subjected to further reaction. Thus, the
recycled catalyst could be used for five successive
reactions without appreciable loss of activity.
Although water is a desirable solvent for chemical
reactions for reasons of cost, safety, and environ-
mental concerns, use of water in this reaction gave
only moderate yields of products (30% after 24 h).
Table 1. Synthesis of quinoxaline derivatives using the Wells-
Dawson heteropolyacid H6P2W18O62 Á 24H2O as the catalyst
Product
R
R1
Time=min Yield=%a,b mp=ꢀC
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
H
H
H
CH3
NO2
COOH
H
5
5
5
10
20
20
20
5
98
98
98
97
98
97
98
99
98
99
97
128–129
117–118
193–194
272
151–152.5
125–127
192–194
135–137
165–167
174–176
230
Experimental
All chemicals were purchased from commercial suppliers and
were used as received. All products were identified by their
spectra and physical data. Melting points were measured by
using the capillary tube method with an electrothermal 9100
apparatus. IR spectra were recorded from KBr disks on the
FT-IR Brucker Tensor 27. Mass spectra were recorded on MS
5973 Network Mass Selective detector. All yields were calcu-
lated from isolated products, and GC was used to establish
their purities. All products were well characterized by com-
parison of TLC, spectral and physical data with data of
authentic samples [26–30].
H
OCH3
OCH3 CH3
OCH3 NO2
F
F
F
F
H
CH3
NO2
COOH
5
2
5
3j
3k
a
1
All products were well characterized using H NMR and
b
IR spectra; Yields refer to isolated pure products

Wells-Dawson Type Heteropolyacid Catalyzed Synthesis
467
[9] Bailly C, Echepare S, Gago F, Waring MJ (1999) Anti-
Cancer Drug Des 15: 291
Preparation of Quinoxalines Catalyzed by Wells-Dawson
Heteropolyacid (General Procedure)
[10] Sato S, Shiratori O, Katagiri K (1967) JAntibiot 20: 270;
and reference cited therein
[11] Porter AE (1984) In: Katritzky AR, Rees CW (eds)
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cycl Chem 22: 367
In this condensation reaction, 1 mmol o-phenylenediamine
and 1 mmol 1,2-dicarbonyl compound were dissolved in
3 cm3 acetic acid. The mixture was stirred at room tempera-
ture in the presence of a catalytic amount of Wells-Dawson
H6P2W18O62 Á 24H2O (1mol%, 0.03g). The progress of the
reaction was monitored by TLC. After completion of the reac-
tion, the catalyst was filtered off and washed with 5 cm3 Et2O.
The filtrate then was washed with 5% NaHCO3 (5cm3) and
brine (2Â5 cm3) successively, and dried over MgSO4. The
solvent was evaporated under reduced pressure and the pure
product was obtained. A variety of substituted o-phenylene-
diamines were condensed with different 1,2-dicarbonyl com-
pounds. The results are shown in Table 1.
[14] Woo GHC, Snyder JK, Wan ZK (2002) Prog Heterocycl
Chem 14: 279
[15] Wu Z, Ede NJ (2001) Tetrahedron Lett 42: 8115
[16] Brown DJ (2004) Quinoxalines: Supplement II. In:
Taylor ECP, Wipf P (eds) The Chemistry of Heterocyclic
Compounds. John Wiley & Sons, New Jersey
[17] Romanelli GP, Autino JC, Baronetti G, Thomas H
(2004) Synth Commun 34: 3909
Reusability of the Catalyst
At the end of the reaction, the catalyst was filtered off, washed
with diethyl ether, dried at 130ꢀC for 1 h, and re-used in
another reaction (Table 2).
[18] Romanelli G, Autino JC, Baronetti G, Thomas H (2001)
Molecules 6: 1006
[19] Baronetti G, Briand L, Sedran U, Thomas H (1998) Appl
Catal A 172: 265
Acknowledgements
The authors are thankful to Azzahra University Council for the
partial financial support.
[20] Heravi MM, Tajbakhsh M, Ahmadi AN, Mohajerani B
(2006) Monatsh Chem 137: 175
[21] Heravi MM, Bakhtiari KH, Taheri SH, Oskooei HA
(2005) Green Chem 7: 867
[22] Heravi MM, Bakhtiari KH, Bamoharram FF (2006)
Catal Commun 7: 373
[23] Heravi MM, Bakhtiari KH, Bamoharram FF (2006)
Catal Commun 7: 499
[24] Bamoharram FF, Heravi MM, Roshani M, Jahangir M,
Gharib A (2006) Appl Catal A 302: 42
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