Nano-BF3·SiO2: A reusable and eco-friendly catalyst for synthesis of quinoxalines

Article abstract of DOI:10.1007/s10593-011-0785-1

2,3-Disubstituted quinoxalines were synthesized via condensation of α-diketones and 1,2-phenylenediamines. Nano-BF₃·SiO ₂ as a "green" and reusable solid acid was used as the catalyst for the synthesis of quinoxalines. The reaction was carried out at room temperature under sonication with high to excellent yields.

Full text of DOI:10.1007/s10593-011-0785-1

Chemistry of Heterocyclic Compounds, Vol. 47, No. 4, July 2011 (Russian original Vol. 47, No. 4, April, 2011)
3 2
NANO-BF ·SIO : A REUSABLE AND ECO-FRIENDLY CATALYST
FOR SYNTHESIS OF QUINOXALINES
1
2
1
B. B. F. Mirjalili *, A. Bamoniri , A. Akbari
2
,3-Disubstituted quinoxalines were synthesized via condensation of α-diketones and 1,2-phenylene-
diamines. Nano-BF ·SiO as a "green" and reusable solid acid was used as the catalyst for the synthesis
3
2
of quinoxalines. The reaction was carried out at room temperature under sonication with high to
excellent yields.
Keywords: α-diketones, nano-BF ·SiO , o-phenylenediamines, quinoxaline, sonication.
3
2
The quinoxaline core is present in the structures of many drugs with anticancer [1, 2], antiamoebic [3],
anticonvulsant [4], antimalarial [5], anti-inflamatory, antioxidant [6], and antiprotozoal activity [7]. Some of the
fluorescent dyes [8], electroluminescent materials [9], chemically controllable switches [10], and organic
semiconductors include the quinoxaline moiety [11]. Many protocols have been developed for the synthesis of
quinoxaline derivatives because of the important applications in medicinal chemistry and industry. The best
reported method for the synthesis of quinoxaline is the reaction of arene-1,2-diamine with a 1,2-dicarbonyl
compound in the presence of an acid catalyst. Acetic acid [12], iodine [13], CuSO ·5H O [14], Zn–L-proline
4
2
complex [15], Ni-nanoparticles [16], gallium(III) triflate [17], montmorillonite K10 [18], task-specific ionic
liquids [19], MnCl [20], and ZrO /Ga O /MCM-41 [21] have been applied in the above-mentioned method
2
2
2
3
(
MCM-41 – mesoporous molecular sieves with 3 nm pore diameter).
The use of ultrasound in organic transformations is well known to enhance reaction rates, yields, and
selectivity. Ultrasound facilitates organic transformations at ambient temperatures, which otherwise require
drastic conditions of high temperature and/or pressure.
BF ·Et O as a strong Lewis acid is corrosive, toxic, and volatile, and it also generates considerable
3
2
amounts of waste. In our laboratory, we are investigating the application of Lewis acids such as BF
3
in organic
reactions. Nano-BF ·SiO [22] and BF ·SiO [23–25] are bench-top catalysts that have many advantages such as
3
2
3
2
simple preparation, reusability, easy handling, and being environmentally benign.
In continuation of our investigations of the application of solid acids in organic synthesis, we have pre-
pared nano-BF ·SiO [22] and investigated its efficiency in the synthesis of quinoxalines under room
3
2
temperature or sonication conditions. The reaction of 1,2-phenylenediamine with benzil was investigated first in
order to find the optimal reaction conditions. Reaction at different temperatures and various molar ratios of
_
*
___________
To whom correspondence should be addressed. E-mail: fmirjalili@yazduni.ac.ir.
1
2
Department of Chemistry, College of Science, Yazd University, Yazd, P.O.Box 89195-741, I. R. Iran.
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, I. R. Iran.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 591–596, April, 2011. Original
_
article submitted March 23, 2011.
0
009-3122/11/4704-0487©2011 Springer Science+Business Media, Inc.
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87

reactants in the presence of BF
3 2
·SiO revealed that the best were solvent-free conditions at room temperature
and a ratio of 1,2-phenylenediamine (mmol)–benzil (mmol)–37% nano-BF ·SiO (mg) equal to 1:1:7.5. The
3
2
3 2
feasibility of the ultrasound-assisted synthesis of quinoxaline in the presence of nano-BF ·SiO was also
demonstrated. The obtained results show that sonication in chloroform at room temperature has reduced the
reaction time to 4 min (Table 1).
TABLE 1. Synthesis of 2,3-Diphenylquinoxaline from 1,2-Pheny-
lenediamine (1 mmol) and Benzil (1 mmol) under Various Conditions
NH2
NH2
O
O
Ph
Ph
N
N
Ph
Ph
catalyst
+
Time,
min (h)
Entry*
Catalyst
Solvent
Yield, %
Ref.
1
2
3
4
5
6
7
8
9
28% BF
3
3
3
3
3
3
3
·SiO
2
2
2
2
2
2
2
/ 7.5**
/ 7.5
/ 7.5
/ 7.5
/ 4.0
/ 6.0
/ 7.5

8
8
58
62
95
96
47
56
95
95
92
88
17
27
63
78
48
96
98
98
95
96
97
99
96
99
85
100
97
33% BF
37% BF
45% BF
37% BF
37% BF
37% BF
·SiO
·SiO
·SiO
·SiO
·SiO
·SiO


8

8

8

8


8
37% nano-BF
37% nano-BF
37% nano-BF
3
3
3
·SiO
·SiO
·SiO
2
2
2
/ 2.5
8
nd
/ 2.5, 2 run

8
rd
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
/ 2.5, 3 run

8
37% BF
37% BF
37% BF
37% BF
37% BF
37% BF
3
3
3
3
3
3
·SiO
·SiO
·SiO
·SiO
·SiO
·SiO
2
/ 7.5
/ 7.5
/ 7.5
/ 7.5
/ 7.5
/ 7.5
EtOH
EtOH
8
2
2
2
2
2
5
CHCl
CHCl
CHCl
CHCl
CHCl
3
3
3
3
3
8
3
2
4
37% nano-BF
3
·SiO
2
/ 7.5
4
I
2
2
/ 10 mol %
/ 10 mol %
MeCN
DMSO
3
[13]
[13]
[14]
[14]
[15]
[17]
[12]
[12]
[18]
[21]
I
35
15
8
CuSO
CuSO
4
4
·5H
2
2
O / 10 mol %
O / 10 mol %
2
H O
·5H
EtOH
HOAc
EtOH
MeOH
EtOH
Zn(L-proline) / 10 mol %
Ga(OTf) / 5 mol %
5
3
5
HOAc / 15 ml
5
HOAc / 15 ml
(12)
(2.5)
(2)
Montmorillonite K10 / 10 mol %
H
2
O
ZrO
2
/Ga
2
O
3
/MCM-41/0.2 g
CH
3
CN
_
*
__________
Conditions: room temperature (entries 1–11, 13, 18–23, 26, 27), ultra-
sound, room temperature (entries 12, 14–17), MW (entry 24), reflux
entry 25).
* Mass of the respective BF ·SiO catalyst in mg (entries 1–17).
(
*
3
2
4
88

The reusability of the nano-BF
3 2 3
·SiO catalyst was also examined. After each run, CHCl was added, the
product was filtered, the solvent evaporated, and the residue on filter (catalyst) was washed with CHCl and
3
reused. Apparently, the treatment with CHCl
3
efficiently removes tar from the catalyst surface (Table 1, entries
9
and 10). This catalyst was reusable, although a gradual decline in activity was observed.
The applicability of the present method for larger-scale preparations was examined. We have condensed
2
0 mmol of 1,2-phenylenediamine and 20 mmol of benzil in the presence of 0.3 g of 37% nano-BF ·SiO under
3
2
solvent-free conditions at room temperature, which gave 2,3-diphenylquinoxaline in 93% yield. To extend the
reaction to substrates with different substituents, three substituted 1,2-phenylenediamines and four 1,2-diketones
were used for the synthesis of quinoxalines under solvent-free conditions at room temperature or under
sonication conditions (Table 2).
The same method can be applied to the reaction of α-hydroxy ketones with 1,2-phenylenediamines for a
two-step synthesis of quinoxalines. For the reaction of 1,2-phenylenediamine with benzoin, the best were
solvent-free conditions at room temperature and a ratio of 1,2-phenylenediamine (mmol)–benzoin (mmol)–
nano-BF ·SiO (mg) equal to 1:1:10. The subsequent oxidation of the intermediate 2,3-diphenyl-1,2-
3
2
dihydroquinoxaline with trichloromelamine gave 2,3-diphenylquinoxaline identical to that obtained from benzil
Scheme).
Nano-BF ·SiO is an easily available, noncorrosive, eco-friendly, and reusable solid acid. In this article,
(
3
2
we have reported a mild, fast, and efficient method for the preparation of quinoxalines from α-diketones and
,2-phenylenediamines using catalytic amount of nano-BF ·SiO . These reactions are characterized by good yields
1
3
2
and short reaction times. In contrast to other acids, this reagent does not need special precautions for handling or
storage, and it can be stored at ambient temperature for at least 6 months without loss of its catalytic activity.
TABLE 2. Synthesis of Quinoxaline in the Presence of nano-BF
Room Temperature (Method A) or under Sonication (Method B)
3 2
·SiO , at
X
NH2
NH2
O
O
R
R
.
X
N
N
R
R
37% nano-BF3
Solvent-free,
SiO2
+
room temperature
or sonication
Product*
Yield, %
Entry
mp, °C
Ref.
2
R
X
A*
B
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
H
95
96
90
94
92
93
98
98
95
85
80
96
93
92
89
90
84
92
97
91
92
90
127–128
115–116
191–92
151–152
126–127
192–193
134–135
164–165
175–176
98–99
[12]
[19]
[19]
[15]
[15]
[15]
[16]
[16]
[16]
Me
NO
H
2
4-MeOC
4-MeOC
4-MeOC
6
6
6
H
H
H
4
4
4
Me
NO
2
4-FC
4-FC
4-FC
6
6
6
H
H
H
4
4
4
H
Me
NO
2
1
0
1
Me
Me
H
[21, 17]
[20]
1
NO
2
135–136
_
*
_____________
All the products are known and were characterized by comparison of
their physical properties with those reported in the literature.
2
*
Method A, time, min: 8 (entries 1–9), 10 (entry 10), 13 (entry 11).
4
89

OH
NH2
.
N
N
N
37% nano-BF3
SiO2
TCM
+
Solvent-free
Solvent-free
O
NH2
N
H H
TCM – trichloromelamine
EXPERIMENTAL
The products were characterized by comparison of their physical properties with those reported in the
literature. Melting points were determined on a Buchi B-540 apparatus. BANDELIN Sonopuls HD 3200
ultrasonic apparatus (20 kHz, 150 W) was used for sonication. BF ·SiO and nano-BF ·SiO were prepared as
3
2
3
2
described earlier [22].
Synthesis of Quinoxaline (General Method). A. A mixture of 1,2-phenylenediamine (2 mmol), benzil
2 mmol), and nano-BF ·SiO (0.015 g) was stirred at room temperature for 8 min. The reaction was monitored
(
3
2
by TLC. After completion of the reaction, the mixture was diluted with chloroform (10 ml) and filtered to
recover the catalyst. The solvent was evaporated and the crude product recrystallized from ethanol (10 ml) to
afford pure quinoxaline derivatives.
B. The mixture of 1,2-phenylenediamine (2 mmol), benzil (2 mmol), nano-BF ·SiO (0.015 g), and chlo-
3
2
roform (10 ml) was placed in a flat bottom flask and irradiated in the ultrasonic apparatus for 4 min. After
completion of the reaction, the mixture was filtered to recover the catalyst, the solvent was evaporated, and the
residue was crystallized from ethanol (10 ml). All products were known and were identified by comparison of
their physical and spectral data with those of authentic samples.
2
,3-Diphenyl-1,2-dihydroquinoxaline. 1,2-Phenylenediamine (1 mmol), benzoin (1 mmol), and 37%
nano-BF ·SiO (0.01 g) were mixed at room temperature. After completion of the reaction, the mixture was
3
2
washed with ethanol (10 ml) on the filter. The filtrate was evaporated and the crude 2,3-diphenyl-1,2-dihyd-
roquinoxaline was used without further purification.
Oxidation of 2,3-Diphenyl-1,2-dihydroquinoxaline. 2,3-Diphenyl-1,2-dihydroquinoxaline (0.028 g,
0
.1 mmol) and trichloromelamine (0.05 mmol) were mixed at room temperature. The progress of the reaction
was monitored by TLC. After completion of the reaction, the mixture was washed with ethanol (10 ml) on the
filter. The filtrate was concentrated to obtain 2,3-diphenylquinoxaline. Yield 81% (2 steps).
The Research Council of Yazd University is gratefully acknowledged for the financial support for this
work.
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