MnCl2-promoted synthesis of quinoxaline derivatives at room temperature

Article abstract of DOI:10.1002/hc.20401

MnCl₂ efficiently catalyzes the condensation of o-phenylenediamine derivatives with 1,2-diketones at room temperature to afford the corresponding quinoxaline derivatives in high yields.

Full text of DOI:10.1002/hc.20401

Heteroatom Chemistry
Volume 19, Number 2, 2008
M
nCl -Promoted Synthesis of Quinoxaline
2
Derivatives at Room Temperature
Majid M. Heravi, Khadijeh Bakhtiari, Hossein A. Oskooie,
and Shima Taheri
Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran
Received 11 June 2006; revised 17 December 2006
conditions. However, many improved methods have
been reported for the synthesis of quinoxalines us-
ing catalytic amount of variety of metal precursors,
acids, zeolites, and molecular iodine [10–12]. These
methods have their own merits and drawbacks.
Very recently, we have developed convenient and
efficient procedures for the synthesis of quinoxaline
derivatives using cupric sulfate pentahydrate, IBX,
and Zn [l-proline] as catalysts [13].
ABSTRACT: MnCl efficiently catalyzes the conden-
2
sation of o-phenylenediamine derivatives with 1,2-
diketones at room temperature to afford the cor-
responding quinoxaline derivatives in high yields.
ꢀ
2
C
2008 Wiley Periodicals, Inc. Heteroatom Chem 19:218–
20, 2008; Published online in Wiley InterScience
(
www.interscience.wiley.com). DOI 10.1002/hc.20401
As part of our ongoing interest in synthesis of
heterocyclic compounds containing nitrogen [14],
in this communication, we report a facile method
for the synthesis of quinoxaline derivatives by the
INTRODUCTION
Quinoxaline and their derivatives are an impor-
tant class of bioactive molecules and are widely
used as anticancer and anthelmintic agents [1], an-
tiviral, antibacterial [2], anti-inflammatory, and as
kinase inhibitors [3]. They have been reported for
their applications in dyes [4], pharmaceuticals [5],
and have been used as building blocks for the syn-
thesis of organic semiconductors [6], and they also
serve as useful rigid subunits in macrocyclic recep-
tors or molecular recognition [7] and chemically
controllable switches [8]. By far, the most common
method used for the synthesis of quinoxaline is based
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 [9].
Nevertheless, most of these methods suffer from un-
satisfactory product isolation procedures, expensive
detrimental metal precursors, and harsh reaction
ꢁ
condensation of 1,2-phenylenediamines with 4,4 -
disubstituted benzils catalyzed by MnCl
temperature.
2
at room
RESULTS AND DISCUSSION
A mixture of benzil (1 mmol), o-phenylenediamine
1 mmol), and a catalytic amount of MnCl (0.01 g,
0 mol%) was stirred in EtOH at ambient temper-
(
2
1
ature and after 17 min the mixture was solidified.
At this stage, TLC analysis showed that both reac-
tants have been completely consumed and the cor-
responding quinoxaline 3 was formed. After that,
the reaction was heated, the product was dissolved
in ethanol, and the catalyst was separated easily
from the reaction mixture without any further re-
crystallization; the pure product was obtained in
9
4% yield. To establish the generality of the pro-
Correspondence to: Majid M. Heravi; e-mail: mmh1331@
yahoo.com.
c 2008 Wiley Periodicals, Inc.
cedure, in a similar manner, other 4-substituted
1,2-phenylenediamines also reacted smoothly with
ꢀ
218

Mncl -Promoted Synthesis of Quinoxaline Derivatives at Room Temperature 219
2
SCHEME 1
ꢁ
4
,4 -disubstituted benzils to afford the correspond-
General Procedure for the Preparation
of Quinoxalines
ing quinoxalines in excellent yields (Scheme 1;
Table 1).
The results listed in Table 1 show that different
kinds of quinoxaline are prepared with ease in ex-
cellent yields. The reaction proceeds very cleanly
at room temperature and no undesirable side
products are observed. In the absence of MnCl , the
reaction did not proceed even after prolonged reflux
condition.
A mixture of 1,2-diketone 1 (1 mmol), 1,2-
diaminoarene 2 (1 mmol), and MnCl (10 mol%) in
2
EtOH (3 mL) was stirred at room temperature. The
progress of the reaction was monitored by TLC. After
completion of the reaction, the mixture was heated,
the product dissolves in ethanol, and the catalyst is
separated easily from the mixture. The pure product
2
3
was crystallized from ethanol. The products were
In summary, we describe a simple, efficient,
straightforward, and one-pot method for the syn-
characterized by spectra and physical data.
thesis of quinoxalines via MnCl -catalyzed conden-
2
sation ofa variety of 1,2-diamines and α-diketone
derivatives. The ambient conditions, high reaction
rates, excellent product yields, and easy work-up
procedure which avoids the use of corrosive solvents,
not only make this methodology an alternative plat-
form to the conventional acid/base catalyzed ther-
mal processes, but also make it significant under
the umbrella of environmentally greener and safer
processes.
Physical and Spectroscopic Data
for Selected Compounds
◦
◦
1
2
,3-Diphenylquinoxaline (1): mp = 128 C–129 C; H
NMR (CDC1
3
, 300 MHz) δ (ppm): 8.2 (dd, J = 3.43,
6
.30 Hz, 2H), 7.79 (dd, J = 3.43, 6.30 Hz, 2H), 7.55
−1
(
m, 4H), 7.39 (m, 6H); IR (KBr) νmax (cm ): 3055,
1541, 1345, 768, 729.
6
-Nitro-2,3-diphenylquinoxaline
(3):
mp =
◦
◦
1
1
9
1
93 C–194 C; H NMR (CDC1
3
, 300 MHz) δ (ppm):
.2 (d, J = 2.38 Hz, 1H), 8.53 (dd, J = 2.50, 9.10 Hz,
EXPERIMENTAL
H,), 8.39 (d, J = 9.17 Hz, 1H), 7.6 (m, 4H), 7.42 (m,
−
1
Melting points were measured by using the capillary
tube method with an electro thermal 9200 appara-
6H); IR (KBr) νmax (cm ): 3057, 2935, 1621, 1341,
1135, 699.
1
tus. H NMR spectra were recorded on a Bruker AQS
6-Methyl-2,3-diphenylquinoxaline (5): mp =
◦
◦
1
AVANCE-300 MHz spectrometer using TMS as an
117 C–118 C; H NMR (CDC1 , 300 MHz) δ (ppm):
3
internal standard (CDCl
recorded from KBr disk on the FT-IR Bruker Tensor
7. All products were characterized by spectra and
physical data.
3
solution). IR spectra were
8.1 (d, J = 8.55 Hz, 1H), 7.96 (s, 1H), 7.63 (dd,
J = 1.72, 8.56 Hz, 1H), 7.5 (m, 4H), 7.35 (m, 6H),
−
1
2
2.6 (s, 3H); IR (KBr) νmax (cm ): 3063, 1660, 1592,
1210, 874, 719, 640.
TABLE 1 Synthesis of Quinoxaline Derivatives Catalyzed by MnCl2
R1
R2
Producta
Time (min)
Yield (%)b
MP ( C)
◦
Entry
1
2
3
4
5
6
H
MeO
H
MeO
H
MeO
H
H
NO2
NO2
CH3
CH3
2,3-Diphenylquinoxaline
2,3-Bis(4-methoxyphenyl) quinoxaline
6-Nitro-2,3-diphenylquinoxaline
2,3-Bis(4-methoxyphenyl)-6-nitro quinoxaline
6-Methyl-2,3-diphenylquinoxaline
2,3-Bis(4-methoxyphenyl)-6-methyl quinoxaline
17
15
17
15
15
10
94
93
92
90
92
91
128–129
151–152.5
193–194
192–194
117–118
125–127
a
1
All products were well characterized using H NMR and IR spectra.
Yields refer to isolated pure products.
b
Heteroatom Chemistry DOI 10.1002/hc

220 Heravi et al.
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Heteroatom Chemistry DOI 10.1002/hc