Green and Eco-Friendly Synthesis of Quinoxalines by Br?nsted Acidic Ionic Liquid Supported on Nano-SiO2 under Solvent-Free Conditions

Full text of DOI:10.1080/00304948.2018.1462056

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
ISSN: 0030-4948 (Print) 1945-5453 (Online) Journal homepage: http://www.tandfonline.com/loi/uopp20
Green and Eco-Friendly Synthesis of Quinoxalines
by Brönsted Acidic Ionic Liquid Supported on
Nano-SiO under Solvent-Free Conditions
2
Seyed Arash Hosseini Daragahi, Razieh Mohebat & Mohammad Hossein
Mosslemin
To cite this article: Seyed Arash Hosseini Daragahi, Razieh Mohebat & Mohammad Hossein
Mosslemin (2018) Green and Eco-Friendly Synthesis of Quinoxalines by Brönsted Acidic Ionic
Liquid Supported on Nano-SiO under Solvent-Free Conditions, Organic Preparations and
2
Procedures International, 50:3, 301-313, DOI: 10.1080/00304948.2018.1462056
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Organic Preparations and Procedures International, 50:301–313, 2018
Copyright Ó Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2018.1462056
Green and Eco-Friendly Synthesis of Quinoxalines
by Br €o nsted Acidic Ionic Liquid Supported
on Nano-SiO under Solvent-Free Conditions
2
Seyed Arash Hosseini Daragahi, Razieh Mohebat, and Mohammad
Hossein Mosslemin
Department of Chemistry, Yazd Branch, Islamic Azad University, Yazd, Iran
Quinoxalines are a class of nitrogen containing heterocycles that have attracted significant
attention due to their prolific bioactivity profiles. They have anti-tubercular, anti-HIV,
anti-inflammatory, antimalarial, anticancer, antidepressant, antibacterial and antifungal
1
–3
activities (Figure 1). Quinoxalines feature in numerous therapeutic agents (e. g., echi-
nomycin, levomycin and actinoleutin) and natural products (e. g., vitamins, alkaloids and
4
–8
antibiotics).
In addition, molecular architectures that incorporate the quinoxaline framework have
9
–11
demonstrated the potential of this unit in diverse areas of materials science.
Fusion of
the quinoxaline moiety with another ring system and covalent attachment to other bioac-
tive fragments such as indole, leads to compounds with diverse pharmaceutical proper-
1
2–14
ties.
Due to the biological activities of quinoxalines and their applications in the pharma-
ceutical, agriculture and chemical industries, there has been increasing attention from
synthetic organic and medicinal chemists to develop newer and more effective methodol-
1
5–18
ogies for this privileged class of compounds.
Indeed, many methods have been pub-
1
9
lished for the synthesis of quinoxalines. The most common strategy for the synthesis of
quinoxalines involves the reaction of o-phenylenediamine with 1, 2-diketones, a-hydrox-
yketones, a-haloketones, or 1,2-diols in the presence of Lewis or Br €o nsted acid cata-
2
0–22
lysts.
However, most of these methods need prolonged reaction times, high
temperatures or harsh conditions. Consequently, the development of an efficient and
convenient method using a reusable catalyst for the synthesis of these heterocyclic
compounds is highly desirable.
At the same time, there is an ongoing demand for the development of green and eco-
friendly methods in organic synthesis. Due to the favorable properties of ionic liquids,
such as high polarity, high thermal and chemical stability, non-flammability and low
vapor pressure, the application of ionic liquids as green media and catalysts in chemical
and biochemical transformations is highly desirable. Among the ionic liquids, sulfonic
acid (—SO H)-functionalized Br €o nsted acidic ionic liquids have attracted considerable
3
3,24
2
attention.
Received December 6, 2016; in final form November 13, 2017.
Address correspondence to Razieh Mohebat, Department of Chemistry, Yazd Branch, Islamic
Azad University, Yazd, Iran. E-mail: mohebat@iauyazd.ac.ir
3
01

3
02
Mohebat et al.
Figure 1 Quinoxaline derivatives with biological activity.
Although the utility of ionic liquids as both solvents and catalysts has been amply
demonstrated, several drawbacks, such as separation and reusability limitations, have
restricted their widespread practical application. These limitations can be overcome by
the immobilization of ionic liquids on solid supports, which provide the advantages of
both ionic liquids and heterogeneous catalysts, including the ease of work-up and
2
5–28
reusability of the catalysts.
As part of our ongoing research towards privileged scaffolds, we report here a facile
and integrated strategy to synthesize diverse quinoxalines using Br €o nsted acidic ionic
liquids supported on nano-SiO under solvent-free conditions (Scheme 1).
2
Scheme 1 Synthesis of quinoxalines by Br €o nsted acidic ionic liquid supported on nano-SiO under
2
solvent-free conditions.
The synthesis of the catalyst was performed in four steps, as illustrated in Scheme 2.
Scheme 2 Preparation of Br €o nsted Acidic Ionic Liquid@nano-SiO
(BAIL@nano-SiO ).
2 2

Synthesis of Quinoxalines
303
The catalyst was characterized by the means of FT-IR spectroscopy, elemental
analysis and SEM images. The FT-IR spectra of nano-SiO (a), nano-SiO bonded
2
2
n-propyl chloride (b), n-propyl-4-aza-1-azoniabicyclo[2.2.2]octane chloride immobi-
lized on nano-SiO (c) and Br €o nsted acidic ionic liquid@nano-SiO (d) are presented
2
2
in Figure 2.
In the spectrum of nano-silica bonded n-propyl chloride, absorbances at 1477
¡
1
and 1245 cm indicate the presence of CH bending and Si–C stretching, respec-
2
¡
1
tively. The bands at around 3000, 3069 and 2844 cm are attributed to the C–H
stretching vibrations of the alkyl moieties. For silica (a), silica bonded n-propyl
chloride (b), n-propyl-4-aza-1-azoniabicyclo[2.2.2]octane chloride immobilized on
SiO (c), and Br €o nsted acidic ionic liquid@nano-SiO , the bands due to the Si–O–Si
2
2
¡
1
stretching vibrations are observed at about 1105 and 810 cm , and a broad band
¡
1
belonging to the Si–OH groups and adsorbed water is seen at around 3436 cm
For n-propyl-4-aza-1-azoniabicyclo[2.2.2]octane chloride immobilized on nano-SiO ,
.
2
¡1
C
¡1
the IR spectra shows C–N stretching at 1660 cm , C-N stretching at 1155 cm ,
1
CH2 bending at 1477 cm , and Si–O stretching at 1070 cm as a broad band.
¡
¡1
These characteristic bands are not observed in the FT-IR spectrum of silica and sil-
ica bonded n-propyl chloride. In the spectrum of Br €o nsted acidic ionic liquid@nano-
¡
1
SiO the bands at 2948 cm belong to the C–H stretching vibrations of the alkyl
2
moieties. The bands due to the S D O stretching vibrations are observed at about
¡
1
401 cm .
1
Figure 2 FT-IR spectra of nano-SiO (a), nano-SiO bonded n-propyl chloride (b), n-propyl-4-aza-
2
2
1-azoniabicyclo[2.2.2]octane chloride immobilized on nano-SiO
liquid@nano-SiO (d).
(c), and Br €o nsted acidic ionic
2
2

3
04
Mohebat et al.
Figure 3 SEM images of: (a) nano- SiO
2 2
and (b,c) BAIL@nano-SiO .
The scanning electron microscope (SEM) images of nano-silica and BAIL@nano-
SiO revealed that the surface morphology of the two samples is different (Figure 3).
2
The differences in SEM images illustrate that immobilization and supporting of IL on
nano-SiO changes the morphological structure of nano-SiO surface considerably, sug-
2
2
gesting that the Br €o nsted acidic ionic liquid was successfully immobilized on nano-SiO2.
To evaluate the efficacy of our new catalyst, the reaction of a-haloketones with 1,2-
phenylendiamines for the synthesis of quinoxalines was studied. To obtain the optimal
reaction conditions, the reaction of a-bromoacetophenone (1 mmol) with 1,2-phenylendi-
amine (1 mmol) in the presence of different ionic liquids, Lewis acids and BAIL@nano-
SiO (35 mol%) was selected as a model and results are summarized at Table 1.
2
As shown in Table 1, Entry 9, the best results were achieved when we used BAIL@-
nano-SiO and it was found to be the most efficient catalyst for this reaction. When the
2
reaction was carried out in the absence of the catalyst, starting materials were recovered
(
Table 1, Entry 1). The influence of catalyst loading on the model reaction was
Table 1
Optimization of Reaction Conditions for the Synthesis of 2-phenylquinoxaline
a
Entry
Cat (mol %)
No catalyst
InCl (35)
Reaction conditions
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
240
30
30
30
30
30
30
30
30
30
30
30
—
45
37
61
36
38
49
76
98
98
98
92
3
ZnCl (35)
2
Bi(OTf) (35)
3
[Hmim]HSO (35)
4
[Bmim]BF (35)
4
[Hmim]OTf (35)
BAIL@SiO (35)
2
BAIL@nano-SiO (35)
2
ꢀ
10
11
12
BAIL@nano-SiO (35)
2
60 C
BAIL@nano-SiO (40)
2
r.t.
r.t.
BAIL@nano-SiO (30)
2
a
Isolated yields.

Synthesis of Quinoxalines
305
investigated using 30–40 mol% of catalyst, and the best yield was obtained in the pres-
ence of 35 mol% of catalyst. Finally, the effect of temperature was evaluated for the
model reaction, and room temperature was found to be the optimum.
To probe the efficiency and the scope of our method, we decided to employ different
a-bromoketones and benzil with various 1,2-phenylendiamines for the synthesis of qui-
noxalines and the results are displayed in Tables 2 and 3. The reaction of 1,2-phenylendi-
amines bearing electron-donating as well as electron-withdrawing functionalities
proceeded smoothly and cleanly with a-bromoketones and the corresponding 2-arylqui-
noxalines were obtained in high yields (Table 2, Entries 1–8). For the synthesis of 2,3-
diarylquinoxalines, the reaction of different 1,2-phenylendiamines bearing electron-
donating or electron-withdrawing functionalities proceeded smoothly with benzil
derivatives, and in all cases products were obtained in high yield (Table 3, Entries 1–9).
Recyclability of the catalyst was studied by the reaction of a-bromoacetophenone
(
1 mmol) with 1,2-phenylendiamine (1 mmol) in the presence of BAIL@nano-SiO2
catalyst (35 mol%) in the model reaction. The reaction proceeded smoothly yielding
8–91% of the product at room temperature for six successive runs (Table 4). The activity
9
of the catalyst was not much affected upon recycling six times.
In conclusion, the present protocol provides a novel, efficient, and recyclable procedure
for the preparation of 2-aryl-quinoxalines and 2,3-diaryl-quinoxalines in high yields. The
catalyst can be recovered and reused over several reaction cycles without considerable loss of
reactivity. Easy workup, environmental compatibility, very high activity and reusability of
19,29
catalyst are useful features of the present protocol over previous methods.
Experimental Section
Melting points were determined using a Stuart Scientific SMP2 apparatus and are uncor-
rected. The nanoparticle sizes were measured using scanning electron microscopy
(S-4700 SEM, HITACHI). FT-IR spectra were recorded on a Jasco 6300 instrument in
the range of 400–4000 cm . H and C NMR (400 and 100 MHz) spectra were
¡
1
1
13
recorded on a Bruker Avance 400 MHz spectrometer in CDCl solution. Mass spectra
3
were recorded on an Agilent Technology (HP) spectrometer operating at an ionization
potential of 70 eV. Elemental analysis was performed on a LECO CHNS-932 analyzer.
Synthesis of n-Propyl-4-aza-1-azoniabicyclo[2.2.2]octane Chloride Immobilized on
Nano-SiO2
The synthesis of the catalyst was performed in four steps, as illustrated in Scheme 2. First,
the nano silica (1.0 g) was suspended in dry toluene (10 mL), and then an excess amount
of 3-chloropropyltrimethoxysilane (1.0 mL), and triethylamine (as a catalyst, 0.1 mL)
was added. The suspension was mechanically stirred and refluxed for 48 h. Afterward,
the reaction mixture was cooled to room temperature, transferred to a vacuum glass filter,
and washed with toluene, ethanol–water mixture, deionized water in turn and finally with
ꢀ
methanol. The resulting solid was dried under vacuum at 60 C for 4 h to give silica
bonded n-propyl chloride. Then, 3-chloropropyl@nano-silica (1 g) and 1,4-diazabicyclo
[2.2.2]octane (DABCO) (0.56 g, 5 mmol) were added to a 50 mL round-bottomed flask
containing dry acetone (30 mL), connected to a reflux condenser, and refluxed for 36 h.
Finally, the reaction mixture was cooled to room temperature, transferred to a vacuum
glass filter, and washed with acetone, ethanol, and methanol in turn. The resulting solid

3
06
Mohebat et al.
Table 2
Synthesis of 2-arylquinoxalines Using Br €o nsted Acidic Ionic Liquid Supported on Nano-
SiO under Solvent-free Conditions
2
a
Entry
1
Amine
a-Bromoketone
Product
Time (min) Yield (%)
30
98
2
3
4
30
30
30
98
97
95
5
6
30
30
96
97
7
30
30
87
85
8
a
Isolated yields.

Synthesis of Quinoxalines
307
Table 3
Synthesis of 1,2-diarylquinoxaline Using Br €o nsted Acidic Ionic Liquid Supported on
Nano-SiO under Solvent-free Conditions
2
a
Entry
1
Amine
Benzyl
Product
Time (min) Yield (%)
45
45
45
94
96
91
2
3
4
45
92
5
6
45
45
95
97
(
Continued on next page)

3
08
Mohebat et al.
Table 3
Synthesis of 1,2-diarylquinoxaline Using Br €o nsted Acidic Ionic Liquid Supported on
Nano-SiO under Solvent-free Conditions (Continued)
2
a
Entry
7
Amine
Benzyl
Product
Time (min) Yield (%)
45
92
8
45
45
92
84
9
a
Isolated yields.
ꢀ
was dried under vacuum at 50 C for 4 h to give n-propyl-4-aza-1-azoniabicyclo[2.2.2]
octane chloride immobilized on nano-SiO as a white powder.
2
Preparation of Nano-SiO Based Br o€ nsted Acidic Ionic Liquid
2
A solution of n-propyl-4-aza-1-azoniabicyclo[2.2.2]octane chloride@nano-SiO (1.0 g,
2
1
afford a solid zwitterion. The resulting solid was washed with Et O in order to remove
.32 mmol) and 1,3-propanesultone (1.4 mmol) in dry THF was refluxed for 24 h to
2
the unreacted starting materials and dried under vacuum. Then sulfuric acid (1.5 mmol)
ꢀ
was added to the solid zwitterion and the resulting mixture was stirred for 12 h at 150 C
and finally the desired nano-SiO based Br €o nsted acidic ionic liquid catalyst was afforded
2
in quantitative yield with a loading level (1.291 mmol/g) based on elemental analysis.
Sulfur content of Br €o nsted acidic ionic liquid@nano-SiO was 4.08% by elemental
analysis.
2
General Procedure for the Synthesis of 2-Arylquinoxalines (3a-h)
In 25 ml round-bottomed flask, a mixture of 1,2-phenylendiamine (1 mmol), a-bro-
moacetophenone (1 mmol) and BAIL@nano-SiO catalyst (35 mol%) was prepared
2
and the reaction mixture was stirred at room temperature for the time shown in
Table 2. The progress of the reaction was monitored by TLC. After completion of

Synthesis of Quinoxalines
309
Table 4
Recycling of BAIL@nano-SiO Catalyst in the Reaction of a-bromoacetophenone
2
(
1 mmol) with 1,2-phenylendiamine
a
Run
Cycle
Yield (%)
1
2
3
4
5
6
0
1
2
3
4
5
98
96
95
93
92
91
a
Isolated yields.
the reaction, ethyl acetate (5 mL) was added and the catalyst was separated by sim-
ple filtration. The residue was dried over anhydrous Na SO and after evaporation of
solvent the pure product was obtained by recrystallization from ethanol.
2
4
General Procedure for the Synthesis of 2,3-Diarylquinoxalines (5a-i)
In 25 ml round-bottomed flask, a mixture of 1,2-phenylendiamine (1 mmol), benzyl
(1 mmol) and BAIL@nano-SiO catalyst (35 mol%) prepared and the reaction mixture
2
was stirred at room temperature for the appropriate time according to Table 3. The prog-
ress of the reaction was monitored by TLC (eluent: ethyl acetate/petroleum ether, 1:7).
After completion of the reaction, ethyl acetate (5 mL) was added and the catalyst was
separated by simple filtration. Residue was dried over anhydrous Na SO and after evapo-
2
4
ration of solvent the pure product was obtained by recrystallization from ethanol.
Analytical and Spectroscopic Data
ꢀ
30
-Phenylquinoxaline (3a). Pale yellow solid; yield 98%, mp 76–78 C (lit mp 75–
7
2
ꢀ
¡1
1
6 C); FT-IR (KBr): 3041, 1611, 1531, 1493, 1455, 868 cm ; H NMR (400 MHz,
CDCl ): d 9.59 (s, 1H), 8.31 (dd, J D 6.4, 1.2 Hz, 2H), 8.15 (td, J D 8.8, 1.2 Hz, 2H),
3
1
3
.90–7.86 (m, 2H), 7.60–7.64 (m, 3H) ppm; C NMR (100 MHz, CDCl ): d 154.6,
7
3
1
43.7, 136.1, 130.7, 130.0, 129.2, 128.9, 127.5 ppm.
ꢀ
31
-(4-Bromophenyl)quinoxaline (3b). Cream solid; yield 98%, mp 132–134 C (lit mp
2
ꢀ
¡1
1
1
28–131 C); FT-IR (KBr): 3056, 1584, 1537, 1482, 1422, 826 cm
;
H NMR
(
400 MHz, CDCl ): d 8.91 (s, 1H); 8.31 (d, J D 8.4 Hz, 2 H), 8.15 (m, 2H), 7.89 (m, 2H),
3
1
3
7
.82 (d, J D 8.4 Hz, 2H) ppm; C NMR (100 MHz, CDCl ): d 153.1, 142.9, 132.4,
3
1
31.1, 130.4, 129.8, 129.6, 129.1, 125.1 ppm.
ꢀ
32
-(4-Chlorophenyl)quinoxaline (3c). Cream solid; yield 97%, mp 143–144 C (lit mp
2
1
8
ꢀ
¡1
1
44–145 C); FT-IR (KBr): 3029, 1531, 1488, 831 cm ; H NMR (400 MHz, CDCl ): d
3
.97 (s, 1H); 8.08 (d, J D 8.8 Hz, 2 H), 8.05 (d, J D 7.2, 2H), 7.67–7.75 (m, 2H), 7.46 (d,
1
3
J D 8.8 Hz, 2H) ppm; C NMR (100 MHz, CDCl ): d 155.1, 143.77, 131.06, 130.16,
3
1
29.54, 129.23, 129.18, 128.77, 128.35, 128.03 ppm.

3
10
Mohebat et al.
ꢀ
31
-(4-Fluorophenyl)quinoxaline (3d). Yellow solid; yield 95%, mp 120–122 C (lit mp
2
1
8
ꢀ
¡1
1
20–121 C); FT-IR (KBr): 3040, 1509, 1452, 840 cm ; H NMR (400 MHz, CDCl ): d
3
.89 (s, 1 H), 8.61 (d, J D 8.4 Hz, 1 H), 8.57 (d, J D 8.6 Hz, 1H), 7.96 (m, 2H), 7.69 (td,
1
3
J D 7.0, 1.6 Hz, 1H), 7.65 (td, J D 7.0, 1.6 Hz, 1H), 7.37 (m, 2H) ppm; C NMR
(
100 MHz, CDCl ): d 165.9, 151.1, 141.2, 132.1, 131.3, 130.1, 129.9, 129.3, 126.9,
3
1
16.8 ppm.
ꢀ
33
2
mp 140–142 C); FT-IR (KBr): 3056, 1594, 855; H NMR (400 MHz, CDCl ): d 9.61 (s,
-(Naphthalen-2-yl)-Quinoxaline (3e). Yellow solid; yield 96%, mp 139–142 C (lit
1
ꢀ
3
1
7
1
H), 8.66 (s, 1H), 8.45 (d, J D 8.0 Hz, 1H), 8.23–8.20 (m, 2H), 8.01–7.89 (m, 3H), 7.82–
1
.78 (m, 2H), 7.64–7.61 (m, 2H) ppm; C NMR (100 MHz, CDCl ): d 153.2, 144.6,
3
3
43.2, 142.2, 132.3, 131.4, 130.0, 129.8, 129.7, 129.1, 128.3, 127.8, 126.9 ppm.
ꢀ
2
(
-(4-Bromophenyl)-6-chloroquinoxaline (3f). White solid; yield 97%, mp 145–148 C
3
lit mp 148–150 C); FT-IR (KBr): 1591, 961, 845 cm ; H NMR (400 MHz, CDCl ):
3
ꢀ
¡1
1
3
1
3
d 9.34 (s, 1H), 8.41–8.36 (m, 4H), 7.61–7.56 (m, 3H) ppm; C NMR (100 MHz, CDCl3):
d 145.2, 144.1, 143.4, 133.1, 131.6, 131.1, 130.8, 129.9, 129.4, 128.6, 127.9, 124.2ppm.
Methyl 2-(4-bromophenyl)quinoxaline-6-carboxylate (3 g). White solid; yield 87%,
ꢀ
34
mp 136–139 C (lit mp 135–137 C); FT-IR (KBr): 2959, 2875, 1588, 961, 841 cm ;
ꢀ
¡1
1
H NMR (400 MHz, CDCl ): d 9.43 (s, 1H), 8.76 (s, 1H), 8.21 (d, J D 7.0 Hz, 1H), 8.01–
3
1
3
7
d 166.7, 148.6, 147.3, 146.9, 143.2, 134.1, 133.0, 132.4, 132.1, 130.3, 128.7, 128.1,
.78 (m, 3H), 7.68 (d, 2H, J D 7.0 Hz), 3.98 (s, 3H) ppm; C NMR (100 MHz, CDCl ):
3
1
26.6, 54.3 ppm.
Methyl 2-(naphthalen-2-yl)quinoxaline-6-carboxylate (3h). Pale yellow solid; yield
35
ꢀ ꢀ
8
8
1
5%, mp 164–167 C (lit mp 164–166 C); FT-IR (KBr): 2966, 2854, 1568, 996,
¡
1 1
37 cm ; H NMR (400 MHz, CDCl ): d 9.63 (s, 1H), 8.77 (d, 1H, J D 8.6 Hz), 8.66 (s,
3
H), 8.41–8.38 (m, 2H), 7.99–7.89 (m, 1H), 7.86–7.81 (m, 3H), 7.57–7.53 (m, 3H), 3.96
13
(
s, 3H) ppm; C NMR (100 MHz, CDCl ): d 166.1, 149.8, 147.8, 144.1, 143.2, 134.1,
3
1
33.2, 132.6, 132.4, 130.3, 129.1, 128.1, 127.9, 126.9, 125.8, 54.1 ppm.
ꢀ
36
2
1
,3-Diphenylquinoxaline (5a). White solid; yield 94%, mp 127–129 C (lit mp 128–
ꢀ
¡1
29 C); FT-IR (KBr): 1679, 1602, 1259, 1162, 835 cm ; H NMR (400 MHz, CDCl ):
3
1
1
3
d 7.99–8.01 (m, 2 H), 7.79–7.77 (m, 2H), 7.54–7.52 (m, 4H), 729–7.31 (m, 6H) ppm;
NMR (100 MHz, CDCl ): d 154.6, 142.4, 141.3, 132.1, 130.4, 129.7, 129.1, 128.8 ppm.
C
3
ꢀ
6
(
-Methyl-2,3-diphenylquinoxaline (5b). Pale brown solid; yield 96%, mp 114–116 C
3
7
ꢀ
¡1
1
lit mp 116–117 C); FT-IR (KBr): 2943, 1681, 1592, 1261, 1157, 839 cm ; H NMR
(
400 MHz, CDCl ): d 8.12 (s, 1H), 7.78 (d, J D 8.4 Hz, 1H), 7.59 (d, J D 8.4 Hz, 1H),
3
1
3
.51–7.49 (m, 4H), 7.34–7.32 (m, 6H), 2.61(s, 3H) ppm; C NMR (100 MHz, CDCl ): d
7
1
2
3
54.2, 153.1, 142.1, 141.8, 140.3, 139.8, 133.1, 131.7, 130.1, 129.1, 128.9, 127.9, 127.7,
2.1 ppm.
ꢀ
2
(
,3-bis(4-Methoxyphenyl)quinoxaline (5c). Yellow solid; yield 91%, mp 145–148 C
3
8
ꢀ
¡1
1
lit mp 148–150 C); FT-IR (KBr): 2941, 1679, 1602, 1259, 1162, 835 cm ; H NMR
(
400 MHz, CDCl ): d 8.11 (d, J D 7.6 Hz, 2H), 7.89 (d, J D 7.6 Hz, 4H), 7.69 (m, 2H),
3
1
3
6
.96 (d, J D 7.6 Hz, 4H), 3.83 (s, 6H) ppm; C NMR (100 MHz, CDCl ): d 159.7,
3
1
53.1, 141.2, 132.2, 130.4, 128.7, 126.5, 114.6, 55.8, 55.4 ppm.

Synthesis of Quinoxalines
311
2
1
,3-bis(4-Methoxyphenyl)-6-methylquinoxaline (5d). White solid; yield 92%, mp 124–
¡1
ꢀ ꢀ
37
1
27 C (lit mp 123–125 C); FT-IR (KBr): 2939, 1681, 1599, 1160, 839 cm ; H NMR
(
400 MHz, CDCl ): d 7.91 (m, 1H), 7.65–7.45 (m, 6H), 6.90–6.80 (m, 4H), 3.85 (s, 6H),
3
1
3
.84 (s, 3H) ppm; C NMR (100 MHz, CDCl ): d 160.6, 160.3, 152.4, 151.3, 141.0,
2
3
1
40.3, 137.3, 132.1, 131.4, 131.1, 129.4, 129.0, 126.8, 114.0, 113.4, 55.4, 55.3, 22.0 ppm.
ꢀ
,3-bis(4-Fluorophenyl)quinoxaline (5e). White solid; yield 95%, mp 135–138 C (lit
39
2
mp 135–137 C); FT-IR (KBr): 3048, 1602, 1564, 1509, 1349, 1228, 845, 801 cm . H
ꢀ
¡1
1
NMR (400 MHz, CDCl ): d 7.96 (2H, d, J D 6.4 Hz), 7.64 (2H, d, J D 6.4 Hz), 7.27–
3
1
3
7
.32 (4H, m), 6.92 (4H, d, J D 8.8 Hz) ppm; C NMR (100 MHz, CDCl ): d 162.1,
3
1
54.3, 142.1, 136.0, 130.9, 129.8, 129.1, 128.9, 116.2, 114.9 ppm.
2
1
,3-bis(4-Fluorophenyl)-6-methylquinoxaline (5f). White solid; yield 97%, mp 161–
¡1
ꢀ ꢀ
39
1
63 C (lit mp 165–167 C); FT-IR (KBr): 2941, 1679, 1602, 1259, 1162, 835 cm ; H
NMR (400 MHz, CDCl ): d 7.89 (1H, d, J D 8.8 Hz), 7.69 (1H, s), 7.39 (1H, d, J D
3
1
3
8
.8 Hz), 7.28 (4H, d, J D 8.5 Hz), 6.62 (4H, d, J D 8.8 Hz), 2.41 (3H, s) ppm; C NMR
3
(
100 MHz, CDCl ): d 162.0, 154.1, 150.4, 141.2, 141.0, 140.1, 137.1, 135.2, 131.9,
31.9, 131.8, 131.6, 130.5, 128.6, 116.1, 114.4, 22.1 ppm.
1
ꢀ
6
FT-IR (KBr): 1680, 1605, 1256, 1166, 835 cm ; H NMR (400 MHz, CDCl ) d 7.99–
7
-Chloro-2,3-diphenylquinoxaline (5 g). Pale cream solid; yield 92%, mp 116–118 C;
1 1
¡
3
1
3
.97 (m, 2H), 7.86 (dd, J D 8.4 Hz, J D 2.4 Hz, 1H), 7.51–7.47 (m, 10H) ppm; C NMR
(
100 MHz, CDCl ) d 154.4, 153.7, 142.2, 139.1, 139.0, 138.8, 136.1, 136.0, 135.3, 130.6,
3
C
1
8
6
30.1, 129.8ppm; MS (m/z, %): 316 (M );
Anal. Calcd for C H ClN : C, 75.83; H, 4.14; N, 8.84. Found: C, 76.03; H, 4.34; N,
.98.
2
0
13
2
ꢀ
-Bromo-2,3-diphenylquinoxaline (5 h). Pale cream solid; yield 92%, mp 112–114 C;
¡
1 1
FT-IR (KBr): 1683, 1595, 1006, 835 cm ; H NMR (400 MHz, CDCl ): d 8.01–7.98
3
1
3
(
(
m, 2H), 7.84 (dd, J D 8.4 Hz, J D 2.4 Hz, 1H), 7.49–7.46 (m, 10H) ppm; C NMR
100 MHz, CDCl ): d 154.2, 153.4, 139.1, 139.0, 138.8, 136.1, 136.0, 135.3, 130.6,
3
C
1
7
6
30.1, 129.8, 118.1ppm; MS (m/z, %): 360 (M );
Anal. Calcd for C H BrN : C, 66.50; H, 3.63; N, 7.75. Found: C, 66.44; H, 3.49; N,
2
0
13
2
.86.
ꢀ
37
-Nitro-2,3-diphenylquinoxaline (5i). Pale red solid; yield 84%, mp 186–187 C (lit
ꢀ
¡1 1
mp 185–187 C); FT-IR (KBr): 1679, 1602, 1554, 1338, 1259, 1162, 835 cm . H NMR
(
400 MHz, CDCl ): d 8.96 (s, 1H), 8.49 (d, J D 8.4 Hz, 1H), 7.94 (d, J D 8.4 Hz, 1H),
3
1
.53–7.51 (m, 4H), 7.41–7.38 (m, 6H) ppm; C NMR (100 MHz, CDCl ): d 156.2,
3
7
1
3
54.9, 147.6, 144.2, 140.1, 139.1, 131.2, 130.0, 129.9, 128.9, 128.1, 126.1, 123.3 ppm.
Acknowledgment
We gratefully acknowledge financial support from the Research Council of the Islamic
Azad University of Yazd.
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