Efficient synthesis of 2-arylindoles, 2-arylimidazo[1,2-a]pyridines and 2-arylquinoxalines, and their bis-derivatives using [Hmim]OTf ionic liquid supported on nano-silica as a reusable catalyst

Article abstract of DOI:10.1007/s13738-015-0603-2

Abstract An efficient and facile method for the synthesis of 2-arylindoles, 2-arylimidazo[1,2-a]pyridines and 2-arylquinoxalines by the reaction of various α-bromo ketones with anilines, 2-aminopyridine and 1,2-phenylenediamine, respectively, in the presence of N-methylimidazolium trifluoromethanesulfonate ionic liquid supported on nano-silica ([Hmim]OTf@nano-SiO₂) as a reusable catalyst under solvent-free conditions has been developed. The bis-derivatives of these compounds were also prepared efficiently, for the first time, using this catalytic system. All products were obtained in high yields and in short reaction times.

Full text of DOI:10.1007/s13738-015-0603-2

J IRAN CHEM SOC
DOI 10.1007/s13738-015-0603-2
ORIGINAL PAPER
Efficient synthesis of 2‑arylindoles, 2‑arylimidazo[1,2‑a]pyridines
and 2‑arylquinoxalines, and their bis‑derivatives using [Hmim]
OTf ionic liquid supported on nano‑silica as a reusable catalyst
Mohammad Soltani · Iraj Mohammadpoor‑Baltork ·
Ahmad R. Khosropour · Majid Moghadam ·
Shahram Tangestaninejad · Valiollah Mirkhani
Received: 16 January 2015 / Accepted: 5 February 2015
© Iranian Chemical Society 2015
Abstract An efficient and facile method for the synthe-
sis of 2-arylindoles, 2-arylimidazo[1,2-a]pyridines and
2-arylquinoxalines by the reaction of various α-bromo
ketones with anilines, 2-aminopyridine and 1,2-phenylen-
ediamine, respectively, in the presence of N-methylimida-
zolium trifluoromethanesulfonate ionic liquid supported
on nano-silica ([Hmim]OTf@nano-SiO2) as a reusable
catalyst under solvent-free conditions has been developed.
The bis-derivatives of these compounds were also prepared
efficiently, for the first time, using this catalytic system. All
products were obtained in high yields and in short reaction
times.
Keywords 2-Arylindoles · 2-Arylimidazo[1,2-a]
pyridines · 2-Arylquinoxalines · α-Bromo ketones ·
Supported ionic liquid
Introduction
Nitrogen-containing heterocyclic compounds such as
indoles, imidazo[1,2-a]pyridines and quinoxalines are
of significant importance owing to their abundant exist-
ence in natural products as well as their extensive appli-
cations in the fields of pharmaceutical, medicinal, and
synthetic organic chemistry [1–12]. These compounds
also exhibit a wide range of biological properties, such as
Graphical abstract
anti-inflammatory [13–16], antibacterial [17–20], antipro-
tozoal [21–24], antidepressant [25, 26], and antiviral [27–
30] activities. Due to the significant applications of these
heterocyclic compounds, a number of synthetic methods
for their preparation have been reported in the literature
[31–62]. However, some of these methods suffer from dis-
advantages such as long reaction times, usage of expen-
sive and nonrecoverable catalysts, low yields of products
and tedious workup. Consequently, the development of an
M. Soltani · I. Mohammadpoor-Baltork (*) ·
A. R. Khosropour (*) · M. Moghadam · S. Tangestaninejad ·
V. Mirkhani
Catalysis Division, Department of Chemistry, University
of Isfahan, 81746-73441 Isfahan, Iran
e-mail: imbaltork@sci.ui.ac.ir
A. R. Khosropour
e-mail: khosropour@chem.ui.ac.ir
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J IRAN CHEM SOC
Scheme 1 Synthesis of 2-arylindoles, 2-arylimidazo[1,2-a]pyridines and 2-arylquinoxalines and also their bis-derivatives catalyzed by [Hmim]
OTf@nano-SiO2
efficient and convenient method using a reusable catalyst
for the synthesis of these widely used heterocyclic com-
pounds is highly desirable.
400 MHz spectrometer using CDCl3 and DMSO-d6 as
solvent. Elemental analysis was performed on a LECO,
CHNS-932 analyzer.
In the recent years, ionic liquids (ILs) have received
significant attention because of their special character-
istic features such as undetectable vapor pressure, non-
flammability, high thermal stability, wide liquid range,
and the ability to dissolve many organic and inorganic
substances. These compounds have also found many
applications in sensors, batteries, plasticizers, electro-
chemistry, extraction, and absorption [63–69]. In addi-
tion, ionic liquids have been examined extensively in
organic synthesis as reaction media or catalysts [70–73].
Despite their outstanding utilities, reactions involving
homogeneous ILs suffer from drawbacks such as difficult
product isolation, catalyst recovery, and the use of rela-
tively large amounts of ILs. However, 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 such as high
interfacial surface area, ease of handling, separation,
recycling and decreasing the amount of IL utilized in a
potential process [74–77].
Preparation of [Hmim]OTf@nano-SiO2
To a 50-mL round-bottomed flask containing N-methyl-
imidazole (20 mmol, 1.64 g) at 0 °C, trifluoromethane-
sulfonic acid (20 mmol, 1.77 mL) was added dropwise
and the mixture was stirred for 2 h. After completion of
the reaction, the mixture was diluted with chloroform
(20 mL) and filtered. The solid material was washed
with chloroform and dried in vacuum to give N-meth-
ylimidazolium trifluoromethanesulfonate ([Hmim]OTf).
Then, a mixture of nano-silica (1.0 g) and [Hmim]OTf
(0.3 g) in distilled water (20 mL) was stirred for 12 h.
Water was removed under reduced pressure and the cat-
alyst was dried in vacuo to produce the [Hmim]OTf@
nano-SiO2 as a white powder (30 wt % [Hmim]OTf/
nano-silica).
General procedure for the synthesis 2-arylindoles,
2-arylimidazo[1,2-a]pyridines and 2-arylquinoxalines
catalyzed by [Hmim]OTf@nano-SiO2
During the course of our studies toward the synthesis of
heterocyclic compounds [78–82], herein we wish to report
an efficient and convenient method for the synthesis of
2-arylindoles, 2-arylimidazo[1,2-a]pyridines and 2-arylqui-
noxalines and also their bis-derivatives in the presence of
[Hmim]OTf@nano-SiO2 as a reusable catalyst under sol-
vent-free conditions (Scheme 1).
To a mixture of aniline, 2-aminopyridine or 1,2-phenylen-
ediamine (1 mmol) and α-bromo ketone (1 mmol), was
added [Hmim]OTf@nano-SiO2 (0.3 mmol). The reaction
mixture was stirred at 110 °C (in the case of 1,2-phenylen-
ediamine, the reaction was performed at room temperature)
for the appropriate time according to Table 2. The progress
of the reaction was monitored by TLC (eluent: ethyl ace-
tate/petroleum ether, 1:20). After completion of the reac-
tion, ethyl acetate (10 mL) was added and the catalyst was
separated by simple filtration. Evaporation of the solvent
followed by purification of the crude product by column
chromatography on silica gel (eluent: ethyl acetate/petro-
leum ether, 1:20) afforded the pure product.
Experimental section
Melting points were determined using a Stuart Scientific
SMP2 apparatus. FT-IR spectra were recorded on a Nico-
let-Impact 400D spectrophotometer. 1H and 13C NMR (400
and 100 MHz) spectra were recorded on a Bruker Avance
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J IRAN CHEM SOC
Characterization data of some representative compounds
16.23), 287.11 ([M+2]+, 97.32), 285.14 ([M]+, 100),
270.02 (75.02), 77.09 (29.40), 75.04 (93.78), 63.07 (28.76),
57.12 (29.53), 50.10 (82.90). Anal. Calcd for C15H12NBr:
C, 62.96; H, 4.23; N, 4.89. Found: C, 63.05; H, 4.27; N,
4.96.
2-(4-Cyclohexylphenyl)-1H-indole (Table 2, entry
6): Mp178–180 °C. IR (KBr): νmax 3427, 2923, 2854,
1
1655, 1229, 1051, 1026, 1005, 825, 763 cm−1. H NMR
(400 MHz, DMSO-d6): δ 1.26–1.48 (m, 6H), 1.70–1.82
(m, 4H), 2.50–2.51 (m, 1H), 6.83 (d, J = 1.2 Hz, 1H), 6.98
(td, J = 7.6, 0.8 Hz, 1H), 7.08 (td, J = 7.6, 0.8 Hz, 1H),
7.30 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.4 Hz, 1H), 7.77 (d,
J = 8.4 Hz, 2H), 7.88 (d, J = 8.4 Hz, 1H), 11.46 (s, 1H).
13C NMR (100 MHz, DMSO-d6): δ 25.6, 26.3, 33.8, 43.5,
98.0, 111.2, 119.2, 119.8, 121.3, 124.9, 127.1, 128.4, 129.8,
137.0, 137.8, 146.9 MS: m/z (%): 276.14 ([M+1]+, 76.08),
275.08 ([M]+, 100), 232.11 (77.25), 206.09 (85.10), 193.13
(63.53), 165.12 (40.39), 128.14 (15.00), 115.13 (65.10),
90.09 (80.00), 57.17 (73.73). Anal. Calcd for C20H21N: C,
87.23; H, 7.69; N, 5.09. Found: C, 87.31; H, 7.72; N, 5.03.
2-(4-Bromophenyl)imidazo[1,2-a]pyridine (Table
entry 13): Mp 215–217 °C. IR (KBr): νmax 3046, 2955,
2
2857, 1631, 1539, 1464, 1399, 1369, 1063, 933, 824,
1
739 cm−1. H NMR (400 MHz, DMSO-d6): δ 6.91 (td,
J = 7.0, 1.2 Hz, 1H), 7.26 (td, J = 7.0, 1.2 Hz, 1H),
7.58 (J = 9.2 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.93 (d,
J = 8.4 Hz, 2H), 8.46 (s, 1H), 8.53 (dd, J = 6.8, 1.2 Hz,
1H). 13C NMR (100 MHz, DMSO-d6): δ 109.3, 114.7,
119.6, 123.3, 124.7, 125.0, 125.6, 127.3, 129.3, 129.3,
133.5. MS: m/z (%): 274.98 ([M+2]+, 49.80), 273.00
([M]+, 64.71), 271.95 (94.90), 193.12 (84.71), 166.15
(37.65), 115.16 (50.59), 101.11 (75.69), 96.40 (100),
78.10 (98.02), 51.19 (89.41). Anal. Calcd for C13H9N2Br:
C, 57.17; H, 3.32; N, 10.26. Found: C, 57.25; H, 3.37; N,
10.35.
2-(4-Bromophenyl)-5-chloro-1H-indole
(Table
2,
entry 9): Mp 147–149 °C. IR (KBr): νmax 3357, 2928,
1
2859, 1650, 1508, 1284, 1188, 1117, 857, 797, 751. H
NMR (400 MHz, DMSO-d6): δ 7.34 (d, J = 8.4 Hz, 2H),
7.63 (d, J = 8.4 Hz, 2H), 7.90 (dd, J = 8.8, 2.4 Hz, 1H),
8.12 (d, J = 9.2 Hz, 1H), 8.31 (d, J = 2.0 Hz, 1H), 8.63
(s, 1H), 11.12 (s, 1H). 13C NMR (100 MHz, DMSO-d6):
δ 99.5, 116.5, 119.0, 122.3, 123.5, 124.6, 125.3, 126.3,
129.9, 131.8, 135.2, 137.5. MS: m/z (%): 308.96 ([M+2]+,
25.32), 306.96 ([M]+, 100), 271.34 (45.32), 91.08 (26.70),
90.08 (42.23), 63.11 (43.69), 52.12 (50.00), 46.10 (93.28).
Anal. Calcd for C14H9NBrCl: C, 54.85; H, 2.96; N, 4.57.
Found: C, 54.94; H, 2.99; N, 4.51.
1,4-Bis(1H-indol-2-yl)benzene (Table
3
entry 1):
Mp 210–212 °C. IR (KBr): νmax 3440, 3046, 2924,
2853, 1599, 1480, 1349, 1297, 798, 742 cm−1. H NMR
1
(400 MHz, CDCl3): δ 7.00 (t, J = 8.4 Hz, 2H), 7.71 (t,
J = 8.4 Hz, 2H), 7.91 (s, 2H), 7.94 (d, J = 8.4 Hz, 2H),
8.03 (d, J = 8.4 Hz, 2H), 8.07 (d, J = 6.8 Hz, 2H), 8.34
(d, J = 9.6 Hz, 2H), 8.52 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 98.1, 112.0, 118.2, 119.9, 122.0, 122.3, 122.4,
126.2, 127.3, 128.4, 138.5. MS: m/z (%): 310.14 ([M+2]+,
2.52), 309.13 ([M+1]+, 27.24), 308.13 ([M]+, 100), 193.09
(78.02), 116.05 (68.41), 85.15 (85.66), 71.15 (89.66),
57.15 (95.00). Anal. Calcd for C22H16N2: C, 85.69; H, 5.23;
N, 9.08. Found: C, 85.77; H, 5.19; N, 9.15.
2-(4-Bromophenyl)-5-nitro-1H-indole (Table 2, entry
10): Mp 187–189 °C. IR (KBr): νmax 3369, 2951, 2854,
1
1651, 1594, 1331, 1280, 1160, 854, 746 cm−1. H NMR
(400 MHz, DMSO-d6): δ 7.63 (d, J = 7.2 Hz, 2H), 7.79
(d, J = 7.2 Hz, 2H), 7.97 (d, J = 2.4 Hz, 1H), 8.02 (dd,
J = 8.4, 2.4 Hz, 1H), 8.08 (d, J = 7.2 Hz, 1H), 8.24 (d,
J = 3.2 Hz, 1H), 11.54 (s, 1H). 13C NMR (100 MHz,
DMSO-d6): δ 113.4, 116.3, 119.1, 120.2, 125.0, 125.1,
126.2, 128.8, 129.1, 130.1, 135.1, 138.6. MS: m/z (%):
319.78 ([M+4]+, 14.26), 317.78 ([M+2]+, 97.31), 315.82
([M]+, 100), 269.04 (4.32), 189.34 (5.00), 69.15 (34.78),
66.06 (76.32), 46.12 (80.70). Anal. Calcd for C14H9N-
2BrO2: C, 53.02; H, 2.86; N, 8.83. Found: C, 53.10; H,
2.83; N, 8.89.
1,4-Bis(5-chloro-1H-indol-2-yl)benzene (Table 3 entry
2): Mp 215-218 °C. IR (KBr): νmax 3441, 3046, 2923,
2854, 1541, 1478, 1349, 1297, 1094, 1008, 832, 742 cm−1
.
1H NMR (400 MHz, CDCl3): δ 6.80 (d, J = 8.0 Hz, 2H),
7.37 (d, J = 8.0 Hz, 2H), 7.39 (d, 7.6 Hz, 2H), 7.43 (d,
J = 2.4 Hz, 2H), 7.46 (d, 7.6 Hz, 2H), 8.31 (s, 2H), 8.54
(s, 2H). 13C NMR (100 MHz, CDCl3): δ 98.0, 112.1, 118.6,
123.4, 124.1, 125.1, 127.9, 130.0, 131.3, 146.7, 151.1.
MS: m/z (%): 378.06 ([M+2]+, 66.21), 377.06 ([M+1]+,
25.04), 376.05 ([M]+, 100), 341.09 (56.02), 306.13 (6514),
226.05 (78.02), 193.02 (96.00), 165.01 (84.31), 114.99
(50.20), 95.31 (98.30), 83.51 (96.08), 51.02 (85.10). Anal.
Calcd for C22H14N2Cl2: C, 70.04; H, 3.74; N, 7.43. Found:
C, 70.11; H, 3.77; N, 7.49.
2-(4-Bromophenyl)-5-methyl-1H-indole
(Table
2,
entry 11): Mp 103–106 °C. IR (KBr): νmax 3358, 2931,
1
2851, 1647, 1508, 1280, 1162, 1118, 884, 745. H NMR
(400 MHz, DMSO-d6): δ 2.60 (s, 3H), 7.57 (d, J = 8.4 Hz,
2H), 7.63 (dd, J = 8.6, 0.8 Hz, 1H), 7.68 (s, 1H), 7.77 (d,
J = 8.4 Hz, 2H), 8.04 (d, J = 8.4 Hz, 1H), 8.14 (s, 1H),
11.63 (s, 1H). 13C NMR (100 MHz, DMSO-d6): δ 23.8,
99.9, 110.9, 120.7, 121.6, 122.8, 125.5, 129.2, 130.2,
132.2, 136.0, 136.9, 138.0. MS: m/z (%): 289.12 ([M+4]+,
1,4-Bis(5-bromo-1H-indol-2-yl)benzene
entry 3): Mp 217–219 °C. IR (KBr): νmax 3420, 3046,
(Table
3
2923, 2854, 1540, 1480, 1351, 1297, 1094, 1008, 832,
1
742, 688 cm−1. H NMR (400 MHz, CDCl3): δ 6.90 (d,
J = 8.8 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.39 (d, 7.6 Hz,
2H), 7.40–7.44 (m, 4H), 8.31 (d, J = 1.2 Hz, 2H), 8.91 (s,
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J IRAN CHEM SOC
2H). 13C NMR (100 MHz, CDCl3): δ 99.0, 112.4, 118.5,
123.5, 124.1, 125.1, 127.9, 129.9, 131.3, 146.6, 150.9.
MS: m/z (%): 467.95 ([M+2]+, 48.91), 466.95 ([M+1]+,
51.40), 465.95 ([M]+, 100), 464.94 (45.60), 385.04 (85.01),
306.14 (78.23), 270.76 (97.00), 191.06 (78.45), 165.02
(84.10), 136.68 (48.76), 113.01 (59.19), 82.59 (82.45),
69.33 (81.95), 50.02 (93.21). Anal. Calcd for C22H14N2Br2:
C, 56.68; H, 3.03; N, 6.01. Found: C, 56.78; H, 3.00; N,
6.09.
1078, 916, 741 cm−1
.
1H NMR (400 MHz, CDCl3): δ
6.90 (d, J = 6.4 Hz, 2H), 7.26 (t, J = 8.8 Hz, 2H), 7.31
(t, J = 8.4 Hz, 2H), 7.45 (d, J = 7.6 Hz, 2H), 7.54 (t,
J = 8.8 Hz, 2H), 7.98 (d, J = 7.6 Hz, 2H), 8.54 (s, 2H).
13C NMR (100 MHz, CDCl3): δ 109.1, 112.3, 116.6,
124.9, 125.5, 126.9, 127.7, 128.7, 133.9, 145.0. MS: m/z
(%): 312.13 ([M+2]+, 2.30), 311.13 ([M+1]+, 22.21),
310.12 ([M]+, 86.14), 194.19 (66.13), 123.13 (100), 117.05
(41.65), 78.16 (75.81), 57.20 (78.23). Anal. Calcd for
C20H14N4: C, 77.40; H, 4.55; N, 18.05. Found: C, 77.48; H,
4.59; N, 17.97.
1,4-Bis(5-methyl-1H-indol-2-yl)benzene (Table 3 entry
4): Mp 185–187 °C. IR (KBr): νmax 3415, 2930, 2851,
1
1653, 1510, 1282, 1162, 1118, 832, 798, 742 cm−1. H
1,4-Bis(quinoxalin-2-yl)benzene (Table 3 entry 7):
Mp 117–119 °C. IR (KBr): νmax 3030, 2849, 1530, 1491,
NMR (400 MHz, CDCl3): δ 2.69 (s, 6H), 7.31 (s, 2H), 7.66
(s, 2H), 8.03 (d, J = 8.4 Hz, 2H), 8.10 (d, J = 8.4 Hz, 2H),
8.43 (d, J = 8.0 Hz, 2H), 8.52 (s, 2H), 8.74 (d, J = 10.8 Hz,
2H). 13C NMR (100 MHz, CDCl3): δ 29.7, 99.0, 112.5,
118.5, 121.6, 121.9, 125.2, 127.9, 128.9, 129.1, 130.3,
158.7. MS: m/z (%): 338.17 ([M+2]+, 3.4), 337.17
([M+1]+, 26.17), 336.16 (100), 207.10 (91.32), 193.09
(81.54), 131.07 (68.65), 116.06 (91.36), 82.59(68.45),
69.33 (78.25), 50.02 (91.16). Anal. Calcd for C24H20N2: C,
85.68; H, 5.99; N, 8.33. Found: C, 85.75; H, 5.96; N, 8.38.
1331, 1227, 1029, 868, 774 cm−1. H NMR (400 MHz,
1
CDCl3): δ 7.81–7.86 (m, 4H), 8.18–8.23 (m, 2H), 8.24
(t, J = 8.0 Hz, 2H), 8.47 (s, 4H), 9.46 (s, 2H). 13C NMR
(100 MHz, CDCl3): δ 128.3, 129.2, 129.7, 129.9, 130.5,
141.8, 142.2, 143.2. MS: m/z (%): 336.13 ([M+2]+, 3.1),
335.13 ([M+1]+, 24.02), 334.12 ([M]+, 75.16), 206.16
(65.12), 179.16 (61.46), 167.12 (83.67), 149.09 (93.86),
97.19 (69.68), 71.17 (92.27), 57.16 (100). Anal. Calcd for
C22H14N4: C, 79.02; H, 4.22; N, 16.76. Found: C, 79.11; H,
4.19; N, 16.80.
1,4-Bis(5-methoxy-1H-indol-2-yl)benzene (Table
3
entry 5): Mp 195–198 °C. IR (KBr): νmax 3431, 2923, 2851,
1
1650, 1505, 1250, 1051, 1005, 831, 763 cm−1. H NMR
(400 MHz, CDCl3): δ 3.69 (s, 6H), 6.98 (d, J = 8.0 Hz,
2H), 7.43 (d, 8.0 Hz, 2H), 7.80 (s, 2H), 7.97 (d, J = 8.4 Hz,
2H), 8.07 (d, J = 8.4 Hz, 2H), 8.38 (s, 2H), 8.62 (d,
J = 9.6 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 66.8,
112.4, 119.3, 112.0, 127.4, 128.7, 128.8, 129.6, 129.7,
130.3, 130.9, 158.7. MS: m/z (%): 370.16 ([M+2]+, 3.71),
369.16 ([M+1]+, 26.40), 368.15 ([M]+, 41.03), 337.14
(86.26), 307.14 (78.62), 223.17 (23.10), 191.10 (62.15),
116.06 (41.21), 93.06 (100), 77.06 (68.62), 66.07 (71.29),
57.10 (96.00). Anal. Calcd for C24H20N2O2: C, 78.24; H,
5.47; N, 7.60. Found: C, 78.19; H, 5.51; N, 7.55.
Results and discussion
The synthesis of the catalyst was performed in two steps,
as illustrated in Scheme 2. First, an equimolar mixture of
trifluoromethanesulfonic acid and N-methylimidazole was
stirred at 0 °C for 2 h to afford N-methylimidazolium tri-
fluoromethanesulfonate ([Hmim]OTf) as a white powder.
Then, a mixture of nano-silica and [Hmim]OTf in distilled
water was stirred at room temperature for 12 h. Water was
removed in vacuum to produce the supported ionic liquid
([Hmim]OTf@nano-SiO2). The catalyst was characterized
by the means of FT-IR spectroscopy and SEM.
1,4-Bis(imidazo[1,2-a]pyridin-2-yl)benzene (Table
3
entry 6): Mp 159–161 °C. IR (KBr): νmax 3127, 3069,
2928, 2853, 1629, 1508, 1471, 1374, 1266, 1143,
The FT-IR spectra of nano-silica and [Hmim]OTf@
nano-SiO2 are depicted in Fig. 1. The FT-IR spectra of
Scheme 2 Synthesis of [Hmim]
OTf@nano-SiO2 catalyst
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J IRAN CHEM SOC
Fig. 1 FT-IR spectra of: a
nano-SiO2; b IL@nano-SiO2
and c the 5-times reused IL@
nano-SiO2
Fig. 2 SEM images of: a
nano-SiO2 and b [Hmim]OTf@
nano-SiO2
[Hmim]OTf@nano-SiO2 (Fig. 1b) show bands at around
1589 and 1549 cm−1 which are assigned to C=N and C=C
vibrations of the imidazole ring. The bands at around 3160,
2947 and 2888 cm−1 are attributed to the C–H stretching
vibrations of the imidazole and alkyl moieties. Moreover,
the bands related to the S=O and S–O stretching frequen-
differences in SEM images thus, illustrate that immobiliza-
tion and supporting of IL on nano-SiO2 changes the mor-
phological structure of nano-SiO2 surface considerably.
First, the reaction of α-bromo acetophenone (1 mmol)
with aniline (1 mmol) was used as a model to study the
catalytic activity of different ionic liquids (ILs) such as
[Hmim]HSO4, [Hmim]NO3, [Hmim]BF4, [Bmim]Br,
[Hmim]OTf, and supported [Hmim]OTf on the common
silica (60-100 mesh) and nano-silica. The results of these
studies are presented in Table 1. Among these ILs, [Hmim]
OTf supported on nano-silica was found to be the most
efficient catalyst for this reaction. When the reaction was
carried out in the absence of the catalyst, only 5 % of the
desired product was obtained (Table 1, entry 8) which
shows that the presence of the catalyst is necessary for
this reaction. The influence of the catalyst loading on the
model reaction was then investigated using 0.2–0.4 mmol
of [Hmim]OTf@nano-SiO2 and the best yield was obtained
cies are observed at around 1166, 1030 and 641 cm−1
.
These characteristic bands are not observed in the FT-IR
spectrum of nano-silica. For nano-silica and [Hmim]OTf@
nano-SiO2, the bands due to the Si–O–Si stretching vibra-
tions are observed at about 1103 and 810 cm−1 and a broad
band belonging to the Si–OH groups and adsorbed water
is seen at around 3434 cm−1 (Fig. 1a, b). These observa-
tions indicate that IL has been successfully supported on
the nano-silica surface.
The scanning electron microscope (SEM) images of
nano-silica and IL@nano-SiO2 revealed that the surface
morphology of these two samples is different (Fig. 2). The
1 3

J IRAN CHEM SOC
Table 1 Optimization of reaction condition for the synthesis of
2-arylindole
of aniline and 2-aminopyridine for the preparation of
2-arylquinoxalines. Treatment of 1,2-phenylenediamine
with various α-bromo ketones under similar conditions at
room temperature resulted in the formation of the corre-
sponding 2-arylquinoxalines in excellent yields (Table 2,
entries 16–19). It is noteworthy that all the reactions pro-
ceeded very efficiently and cleanly, and no undesirable side
reactions were observed under these conditions.
o
Entry
Catalyst (mmol)
Time (min)
Yield (%)a
Another outstanding feature of this catalytic system
lies in the synthesis of bis-derivatives of the title com-
pounds. As shown in Table 3, condensation of 1 mmol
1,1′-(1,4-phenylene)bis(2-bromoethanone) with 2 mmol
each of anilines, 2-aminopyridine and 1,2-phenylenedi-
amine was performed efficiently in the presence of [Hmim]
OTf@nano-SiO2 under solvent-free conditions, affording
the corresponding bis-2-arylindoles, bis-2-arylimidazo[1,2-
a]pyridine and bis-2-arylquinoxaline in high yields. To the
best of our knowledge, the present report is the first exam-
ple of the use of 1,1′-(1,4-phenylene)bis(2-bromoethanone)
in the synthesis of bis-derivatives of these compounds.
Consequently, this new procedure is of practical impor-
tance and can be considered as a useful achievement in the
synthesis of these fundamental heterocycles.
Typically, the plausible reaction mechanism for the syn-
thesis of 2-arylquinoxaline from 1,2-phenylenediamine and
α-bromo ketone is outlined in Scheme 3. Initially, activa-
tion of the carbonyl group of α-bromo ketone by the cata-
lyst followed by condensation with one amino group of
1,2-phenylenediamine results in imine A. Then, intramo-
lecular nucleophilic attack by the remaining NH2 in imine
A leads to dehydrohalogenation and cyclization, giving
dihydroquionoxaline B. Finally, oxidative aromatization of
intermediate B under ambient atmosphere in the presence
of the catalyst furnishes the desired 2-arylquinoxaline C
and releases the catalyst for the next catalytic cycle.
Finally, the reusability of the catalyst was checked in
the reaction of aniline with α-bromo acetophenone. After
completion of the reaction, the mixture was cooled to room
temperature and ethyl acetate (10 mL) was added. The cat-
alyst was recovered by simple filtration, dried and reused
for subsequent experiments. The results of these experi-
ments show that the catalyst could be recycled and reused
five times without notable decline in its activity (Table 4).
Comparison of the FT-IR spectra of fresh and reused cat-
alysts showed no significant changes in the characteristic
bands, which indicates that the catalyst is stable during the
reaction (Fig. 1b, c).
1
[Hmim]HSO4 (0.3)
30
30
30
30
30
30
30
120
30
30
30
30
50
42
35
31
65
70
95
5
2
[Hmim]NO3 (0.3)
3
[Hmim]BF4 (0.3)
4
[Bmim]Br (0.3)
5
[Hmim]OTf (0.3)
6
[Hmim]OTf@SiO2 (0.3)
[Hmim]OTf@nano-SiO2 (0.3)
–
7
8
9
[Hmim]OTf@nano-SiO2 (0.2)
[Hmim]OTf@nano-SiO2 (0.4)
[Hmim]OTf@nano-SiO2 (0.3)
[Hmim]OTf@nano-SiO2 (0.3)
62
95
78
95
10
11b
12c
a
Isolated yield
b
c
Reaction was performed at 90 °C
Reaction was performed at 120 °C
in the presence of 0.3 mmol of catalyst. Finally, the effect
of temperature was evaluated for the model reaction in the
range of 90–120 and 110 °C was found to be the optimum
temperature.
Encouraged by the efficiency of the above reaction pro-
tocol, we then devised a novel synthesis of 2-arylindoles,
2-arylimidazo[1,2-a]pyridines and 2-arylquinoxalines
under solvent-free conditions. To scrutinize the scope and
generality of this protocol, we initially advocated a vari-
ety of α-bromo ketones with anilines for the synthesis of
2-arylindoles and the results are summarized in Table 2.
As can be seen, the reaction of aniline and anilines bear-
ing electron-donating as well as electron-withdrawing
functionalities proceeded smoothly and cleanly with
electron-withdrawing, and electron-releasing substi-
tuted α-bromo ketones under thermal conditions (110 °C)
and the corresponding 2-arylindoles were obtained in
high yields (Table 2, entries 1–11). With these remark-
able results in hand, we then examined the prepara-
tion of 2-arylimidazo[1,2-a]pyridines in the presence of
[Hmim]OTf@nano-SiO2 catalyst. As shown, 2-amino-
pyridine reacted efficiently with α-bromo ketones under
the identical reaction conditions to generate the desired
2-arylimidazo[1,2-a]pyridines in high yields (Table 2,
entries 12–15). To further expand the scope of application
of this protocol, 1,2-phenylenediamine was used instead
Conclusion
In conclusion, we have successfully developed a con-
venient and environmentally benign synthetic method to
1 3

J IRAN CHEM SOC
Table 2 Synthesis of 2-arylindoles, 2-arylimidazo[1,2-a]pyridines and 2-arylquinoxalines catalyzed by [Hmim]OTf@nano-SiO2
Time
(min)
Mp/oC (Lit)
Yield
(%)a
Entry α -Bromo ketone
Amine
Product
187–189
1b
30
30
30
30
35
95
92
90
95
87
(188–190 [84])
208–211
2b
3 b
4b
5b
(211–213 [84])
204–206
(206–208 [38])
186–188
(185–186 [83])
101–103
( 99–102 [86])
6b
7b
8b
40
40
30
85
86
95
178–180
226–228
(226–227 [87])
293–295
(293–295 [85])
9b
40
60
90
82
147–149
187–189
10b
afford 2-arylindoles, 2-arylimidazo[1,2-a]pyridines and
2-arylquinoxalines and also their bis-derivatives using
[Hmim]OTf@nano-SiO2 as a recyclable and reusable
catalyst under solvent-free conditions. To the best of our
knowledge, this is the first example of synthesizing bis-
derivatives of the title compounds using this catalytic
1 3

J IRAN CHEM SOC
Table 2 continued
11b
30
96
103–106
133–135
(131.6–132.3
[49])
12b
35
91
87
13b
35
215–217
205–207
14b
35
85
(206.5–207
[49])
163–165
(163.1–163.4
[49])
15b
16c
40
40
90
98
75–78
(75–76 [89])
132–134
17c
18c
19c
40
40
40
96
95
98
(128–131 [57])
142-144
(144–145 [88])
120–122
(120–121 [89])
a
Isolated yield
b
α-Bromo ketone (1 mmol), amine (1 mmol), Catalyst (0.3 mmol), 110 °C
c
α-Bromo ketone (1 mmol), 1,2-phenylenediamine (1 mmol), catalyst (0.3 mmol), room temperature
1 3

J IRAN CHEM SOC
Table 3 Synthesis of bis-derivatives of 2-arylindole, 2-arylimidazo[1,2-a]pyridine and 2-arylquinoxaline catalyzed by [Hmim]OTf@nano-SiO2a
Time
(min)
Yield
(%)b
Mp/oC
Entry α-Bromo ketone Amine
Product
1
45
45
45
78
73
70
210-212
2
3
215-218
217-219
4
5
6
7
45
45
45
45
75
73
72
70
185-187
195-198
159-161
117-119
a
1,1′-(1,4-Phenylene)bis(2-bromoethanone) (1 mmol), amine (2 mmol), catalyst (0.5 mmol), 110 °C
b
Isolated yield
1 3

J IRAN CHEM SOC
Scheme 3 Proposed mecha-
nism for the preparation of
2-arylquinoxaline catalyzed by
[Hmim]OTf@nano-SiO2
C
B
A
Table 4 Recycling of [Hmim]OTf@nano-SiO2 in the reaction of ani-
line with α-bromo acetophenonea
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