Manganese(IV) dioxide-catalyzed synthesis of quinoxalines under microwave irradiation

Article abstract of DOI:10.1039/b417556e

We synthesize quinoxalines, catalyzed by manganese(IV) dioxide, from a variety of α-hydroxyketones followed by trapping with aromatic or aliphatic 1,2-diamines without using a solvent, within one minute under microwave irradiation. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b417556e

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Manganese(IV) dioxide-catalyzed synthesis of quinoxalines under
microwave irradiation
So Yeon Kim, Kang Hyun Park and Young Keun Chung*
Received (in Cambridge, UK) 18th November 2004, Accepted 6th December 2004
First published as an Advance Article on the web 20th January 2005
DOI: 10.1039/b417556e
Recently, microwave-assisted reactions have been highlighted
due to their short reaction times compared to those of the
conventionally heated reactions.6,7 Thus, we used microwave as
an energy source in our reaction. As expected, the reaction time
was shortened to 1 min, but with a poor yield. We used
dichloromethane as a solvent in order to compare with the case of
the conventional heating, although dichloromethane has been
known as a poor solvent under microwave heating. We also
screened other solvents such as methanol and water (entries 6
and 7). The use of water as a solvent seemed likely to be unsuitable
because of water condensation reactions. In any case, when water
was used as a reaction medium, the yield was poor. Thus, the
change of the reaction medium did not help the yield of the
reaction. However, when the reaction was carried out without a
solvent (entry 8), the yield was dramatically improved to 81%.
Interestingly, when the reaction was conducted in an open vessel
(entry 9), a much lower yield (36%) was obtained. Thus, all other
reactions were performed in a pressurized reactor. Moreover, with
this technique, when the amount of MnO2 used was cut down to
0.1 mol% (entry 10), the yield was still 63%. Thus, by using
0.1 mol% of MnO2 under microwave irradiation without using a
solvent, the reaction can be carried out within 1 min.
We synthesize quinoxalines, catalyzed by manganese(IV)
dioxide, from a variety of a-hydroxyketones followed by
trapping with aromatic or aliphatic 1,2-diamines without using
a solvent, within one minute under microwave irradiation.
While we have been studying the use of transition metal
nanoparticles in catalysis,1 a recent publication about the
preparation of nanoparticles of MnO/Mn3O4 attracted our
attention.2 Thus, we decided to study the use of nanoparticles of
manganese oxides in catalysis. To begin with, we surveyed the use
of manganese dioxide in organic synthesis. Manganese dioxide is
widely used as an oxidant in many organic reactions.3 Among
them, the work4 reported by Taylor’s group attracted our
attention. Taylor and other researchers used 10 equiv MnO2 in
their oxidation reactions.4,5 For example, quinoxalines have been
prepared by the reaction of a-hydroxyketone (1 equiv) with 1,2-
diamine (2 equiv) in the presence of molecular sieves and MnO2
(10 equiv) in dichloromethane for 90 min.4a We noted that the use
of a large excess of MnO2 may result in the production of chemical
waste. Recently, we found that quinoxalines could be obtained in
high yields within 1 min by using a catalytic amount of MnO2
under microwave irradiation without using a solvent. Thus, as a
result of this study, we have developed an environmentally-friendly
process of quinoxaline production.
Next we screened other a-hydroxyketones under the same
reaction conditions as above (Table 2).8 Most of the reactions went
to completion within 1 min although the yields were highly
dependent upon the substrate used. When a methyl group was
introduced to one of amines (entry 2), a steric effect of the methyl
group might be reflected on the yield, resulting in a moderate
yield (48%). An aliphatic diamine (entry 3) was also as a good
substrate as aromatic diamines. When hydroxy acetophenone
(CH3C(O)CH2OH) was used instead of PhC(O)CH2OH, the
We first studied a reaction between 1,2-diaminobenzene and
2-hydroxyacetophenone (PhC(O)CH2OH) by screening the reac-
tion conditions, including the amount of MnO2, the reaction time,
the reaction temperature, and the solvent (Scheme 1, Table 1).
First, the use of MnO2 was cut down to 10 mol% using
dichloromethane as a solvent (entry 1). As the table shows, the
reaction went to completion without any problems. Moreover, no
diazo compounds were formed as byproducts. When MnO was
used instead of MnO2, the yield (86%) was almost the same. Thus,
both MnO and MnO2 are effective catalysts in the tandem
oxidative reaction. However, due to economic reasons, we chose
commercially available MnO2. The use of manganese oxide
nanoparticles (entry 3) was not helpful for the yield of the
reaction. When 1 mol% of MnO2 was used (entry 4), the yield
was still 53%.
Table 1 Optimization of the reaction conditionsa
Temp/
uC
Yield
(%)b
Entry
Catalyst
Time
Solvent
1
2
3
10 mol % MnO
10 mol % MnO2
10 mol % Mn
100
100
100
3 h
3 h
3 h
CH2Cl2
CH2Cl2
CH2Cl2
86c
88c
78c
nanoparticles
4
5
6
7
8
1 mol % MnO2
1 mol % MnO2
1 mol % MnO2
1 mol % MnO2
1 mol % MnO2
0.1 mol % MnO2
1 mol % MnO2
1 mol % MnO2
100
70
70
70
70
70
70
70
3 h
CH2Cl2
CH2Cl2
MeOH
H2O
—
—
CH2Cl2
—
53c
17
15
21
1 min
1 min
1 min
1 min
1 min
1 min
1 min
81
9
63
10
11
a
19d
36d
Scheme 1
b
Reaction conditions: sealed tube, MW 70 uC. Isolated yield.
c
d
conventional thermal heating. Open tube.
*ykchung@snu.ac.kr
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Chem. Commun., 2005, 1321–1323 | 1321

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Table 2 MnO2-catalyzed formation of quinoxalinesa
Entry
1
a-Hydroxyketones
1,2-Diamines
Product
Yield (%)b
81
2
48c
3
4
5
85
47
59
6
72
7
46
8
42
a
b
c
All reactions were carried out on a 1 mol% scale. Isolated yield. 1-Methyl-3-phenyl-1,2-dihydro-quinoxaline: 1H NMR (CDCl3, 300 MHz):
d 7.95–7.92 (m, 2H), 7.48–7.45 (m, 3H), 7.40–7.37 (m, 1H), 7.14 (td, J 5 7.97 Hz, 1.53Hz, 1H), 6.81 (td, J 5 7.53Hz, 1.22Hz, 1H), 6.69–
6.62 (m, 1H), 4.24 (s, 2H), 2.88 (s, 3H); 13C NMR (CDCl3, 75 MHz): d 130.7, 128.9, 128.7, 128.2, 127.2, 126.4, 118.6, 110.5, 50.1, 37.3; HRMS
for C15H14N2: calcd. 222.1157, obsd. 222.1161.
change of the phenyl group to the methyl group was manifested in
the yield. We envisioned that a furanyl group would be similar
to the phenyl group. However, the yield dropped to 59%.
Introduction of a functional group such as methyl, bromide, and
methoxy to the phenyl group of PhC(O)CH2OH was not helpful
to the yield. A relatively high yield was obtained when a methyl
group was introduced.
Next we investigated the extension of our discoveries to other
similar reactions. A number of synthetic methods have been
developed for the production of 2-substituted benzimidazoles.9
Recently, Wilfred and Taylor reported10 a one-pot procedure for
the preparation of 2-substituted benzimidazoles from activated
alcohols and 1,2-diaminobenzene using an MnO2 tandem oxida-
tion process. However, no catalytic reactions have been reported
1322 | Chem. Commun., 2005, 1321–1323
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Scheme 2
until now. Thus, we applied our discoveries to the synthesis of
benzimidazoles via an MnO2-catalyzed reaction between aldehydes
and 1,2-diaminobenzene (Scheme 2).
5 (a) X. Fernandez and E. Dun˜ach, Tetrahedron: Asymmetry, 2001, 12,
1279; (b) O. Delacroix, B. Andriamihaja, S. Picart-Goetgheluck and
J. Brocard, Tetrahedron, 2004, 60, 1549.
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H. E. Blackwell, Org. Biomol. Chem., 2003, 1, 1251; (c) N. Kuhnert,
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Tetrahedron, 2004, 60, 1309; (c) W.-C. Shieh, S. Dell and O. Repic,
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7859.
The yield was not as high as those in the synthesis of
quinoxalines. However, the expected products were obtained in
reasonable yields within 1 min of reaction time.
In conclusion, we have developed an environmentally friendly
process for the MnO2-catalyzed synthesis of quinoxalines, from a
variety of a-hydroxyketones followed by trapping with aromatic
or aliphatic 1,2-diamines without using a solvent, within 1 min
under microwave irradiation.
This work was supported by the Ministry of Science and
Technology of Korea through Research Center for Nanocatalysis,
one of the National Science Programs for Key Nanotechnology
and by grant No. (R02-2004-000-10005-0(2004)) from the Basic
Research Program of the Korea Science
& Engineering
Foundation. K.H.P. and S.Y.K. give thanks for BK21 fellowships.
8 A typical experimental procedure: To a 10 mL glass vial were added
2-hydroxyacetophenone (0.133 g, 0.97 mmol), 1,2-diaminobenzene
˚
(0.211 g, 1.95 mmol), 4A molecular sieves (1.0 g), and activated
So Yeon Kim, Kang Hyun Park and Young Keun Chung*
Depratmentl of Chemistry, College of Natural Sciences, Seoul National
University, Seoul, 151-747, Korea. E-mail: ykchung@snu.ac.kr;
Fax: +82 2 889 0310; Tel: +82 2 880 6662
MnO2 (Aldrich, product No. 21764-6; 1 mg). The vessel was then heated
to 70 uC under microwave irradiation using the Discover Synthesizer
(monomode microwave cavity at 2.45 GHz; temperature control by
automated adjustment of irradiation power in a range from 0 to 300 W).
After 1 min the vial was cooled to r.t. The solution was filtered and
concentrated under reduced pressure and purified by flash chromato-
graphy on silica eluting with hexane/ether to give 163 mg (81% yield) of
2-phenyl-quinoxaline.
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Notes and references
1 (a) S.-W. Kim, S. U. Son, Y. K. Chung and T. Hyeon, Chem. Commun.,
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(g) K. H. Park, S.-Y. Kim and Y. K. Chung, Org. Lett., 2003, 5, 4967;
(h) K. H. Park, S. U. Son and Y. K. Chung, Org. Lett., 2004, 6, 1183.
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This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 1321–1323 | 1323