Metal-free oxidative coupling of aminopyridines with nitroolefins to imidazo [1,2-α]pyridine in the presence of i2-tbhp-pyridine

Article abstract of DOI:10.1515/znb-2015-0171

A facile metal-free approach to the synthesis of imidazo [1,2-α]pyridine was developed through a tandem reaction of Michael addition and oxidative coupling. Iodine-t-butyl hydroperoxide-pyridine was found to be a green and efficient catalytic system for t

Full text of DOI:10.1515/znb-2015-0171

Z. Naturforsch. 2016; aop
LMitaeo Atna*,lX-ifarojeuneSuon,xMiedngaLtv,iJviaenfecngoZuhopu,lFiennggxiaoZhfuaanmd Hiuni Zohopnyg ridines
with nitroolefins to imidazo[1,2-a]pyridine
in the presence of I2–TBHP–pyridine
DOI 10.1515/znb-2015-0171
nitrogen-containing fused heterocycles and are known
for a plethora of biological and pharmacological proper-
ties [9], such as antidepressant [10], anticancer, antiviral,
antiparasitic, and anti–human immunodeficiency virus
activities. Furthermore, they are also the core structure
of some currently marketed drugs, such as zolimidine,
zolpidem, loprinone, and alpidem. Therefore, much inter-
est has been drawn to develop the imidazo[1,2-a]pyridine
Received October 21, 2015; accepted November 26, 2015
Abstract: A facile metal-free approach to the synthesis
of imidazo[1,2-a]pyridine was developed through a tan-
dem reaction of Michael addition and oxidative coupling.
Iodine–t-butyl hydroperoxide–pyridine was found to be a
green and efficient catalytic system for this approach.
Keywords: imidazo[1,2-a]pyridine; metal free; Michael preparation.
addition; oxidative coupling.
Traditionally, coupling of 2-aminopyridines with
α-halocarbonyl compounds provides a practical method
to imidazo[1,2-a]pyridine [11–13]. This protocol was also
extended to similar α-functionalized ketones [14, 15]. Other
methods included (i) the condensation of 2-aminopyridines
and aromatic ketones [16–18]; (ii) one-pot condensations
of 2-aminopyridines, aldehydes, and isonitriles [19–22];
(iii) three-component reactions of 2-aminopyridines, alde-
hydes, and alkynes [13–25], or oxidative cross-coupling/
cyclization between 2-aminopyridines and terminal
alkynes [26]; (iv) condensation of 2-aminopyridines with
1,3-dicarbonyl compounds [27, 28]; and (v) condensation
of 2-aminopyridines with chalcones [29, 30]. (vi) More-
over, recently, Yan and co-workers have developed a CuBr-
catalyzed method for the preparation of imidazo[1,2-a]
pyridines from aminopyridines and nitroolefins [31]. Sub-
1 Introduction
Metal-catalyzed coupling reactions have provided pow-
erful tools for the formation of carbon–carbon bonds
and carbon–heteroatom bonds to a wide range of com-
pounds in many areas [1–4]. Coupling reactions have been
extensively studied to develop innovative and greener
approaches. Metal-free coupling is an important and
increasingly trendy highlight that has attracted much
attention in recent years [5–7]. Although traditional metal-
catalyzed coupling reactions have been proven effective
in many industrial applications, they are also generat-
ing harmful metal waste and much other organic waste.
In addition, some metal catalysts are moisture and/or air
sensitive. Owing to mild conditions, low cost, and good
efficiency, metal-free catalysts could be candidates for
many green processes in both academic and industrial
research.
sequently, FeCl2
[32] and FeCl3 [33, 34] were developed to
promote the construction of imidazo[1,2-a]pyridine from
in situ–generated or as-prepared nitroolefins. However,
there are very few reports on metal-free catalysts for this
route [35, 36]. In the former example, the authors found
that Bu4NI–TBHP (t-butyl hydroperoxide) was an effi-
cient catalytic system [35]. In the more recent example, a
new protocol was presented in which the cycloaddition
of N-aminopyridines and β-nitroolefins to substituted
pyrazolo[1,5-a]pyridines had been developed [36]. Thus,
a mild, green protocol for the synthesis of imidazo[1,2-a]
pyridine is still desirable. Encouraged by the previous
reports and as a part of our continuing study on metal-
free/catalyst-free reactions in green chemistry [37, 38],
we wish to report herein a metal-free I2–TBHP–pyridine
combination mediated by the formation of imidazo[1,2-a]
pyridine via Michael addition and oxidative coupling.
Imidazo[1,2-a]pyrimidines are important het-
erocyclic compounds [8]. They are prominent among
*Corresponding author: Litao An, Jiangsu Key Laboratory for
Chemistry of Low-Dimensional Materials, College of Chemistry and
Chemical Engineering, Huaiyin Normal University, Huaian 223300,
Jiangsu Province, P.R. China, Tel.: +86 517-83525083,
Fax: +86 517-83525663, E-mail: anlitao@hotmail.com
Xiaojun Sun, Meng Lv, Jianfeng Zhou, Fengxia Zhu and Hui Zhong:
Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials,
College of Chemistry and Chemical Engineering, Huaiyin Normal
University, Huaian 223300, Jiangsu Province, P.R. China
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ꢀꢀꢀꢁ
2ꢀ ꢀL. An et al.: Metal-free oxidative coupling of aminopyridines with nitroolefins
I2–TBHP–Py [40]. However, the model reaction under the
optimal condition without any solvent gave a negative
2 Results and discussion
To begin with our study, the reaction of 2-aminopyri- result (Table 1, entry 6). Besides these trials, other candi-
dine and β-nitrostyrene was chosen as a model reac- dates were also investigated, but they could not lead to
tion to screen the conditions (Table 1). The reaction better results (Table 1, entries 7–12).
occurred at room temperature, resulting in poor yield
The substrate scope then was investigated under the
(Table 1, entry 1). Even at an elevated temperature, the optimized reaction conditions (Table 2). In most cases,
material could not be consumed completely. Inspired the reaction proceeded smoothly in moderate to good
by I2–TBHP in the C–N oxidative coupling [29, 39], the yield. It was observed that some functional groups, such
catalytic system was also tested for the model reaction. as amino, nitro, halo, and methoxy, were tolerable in the
Fortunately, a good yield was achieved (Table 1, entry 2). catalytic system. Generally speaking, 2-aminopyridine
When a catalytic amount of pyridine was added to the resulted in better yields than 3-methyl 2-aminopyridine.
reaction mixture, the material was consumed in shorter It was reported that ortho-substituted nitroolefins did not
time with comparative yield (Table 1, entry 3). When the give the desired imidazo[1,2-a]pyridines in the presence
loading of I2 was increased to 0.2 equiv, a better yield of Bu4NI–TBHP [35]. It is noteworthy that fairly moderate
was given (Table 1, entry 4). Similarly, less TBHP gave yields were achieved for ortho-substituted nitroolefins
poor yield (Table 1, entry 5). It is shown that it may be under our catalytic system (Table 2, 3e, 3m). It was inter-
due to the synergistic effect in the catalytic system of esting that the catalytic system was effective even at room
temperature in some cases (Table 2, 3d–i, 3k, 3m, 3o).
Based on TLC analysis, a reaction at room temperature
Table 1:ꢀOptimization of reaction conditions.a
gave fewer spots than those at elevated temperature in
these cases. Finally, the scope was extended to other sub-
strates (Table 3). As for a heterocycle-substituted nitroole-
fin, it produced a complex mixture (Table 3, entry 1). It
was the same when (E)-(2-nitroprop-1-en-1-yl)benzene was
used instead of β-nitrostyrene (Table 3, entry 2). The reac-
tion of β-nitrostyrene with acetylated 2-aminopyridine did
not occur (Table 3, entry 3). It might be due to reduced
activity of an amino in the presence of an acetyl group.
If the amino was replaced with a benzyl group, only a
NO2
N
cat.
N
+
solvent
O2N
N
NH2
Entryꢁ Catalyst
ꢁ
Solvent
ꢁ
Temp. (°C)ꢁ Reaction ꢁ Yieldb (%)
time (h)
1
2
3
4
5
6
7
8
9
ꢂ I2
ꢂ CH3CN
ꢂ CH3CN
ꢂ r. t.
ꢂ 80
ꢂ 80
ꢂ 80
ꢂ 80
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
24 ꢂ
20 ꢂ
12 ꢂ
12 ꢂ
12 ꢂ
24 ꢂ
24 ꢂ
24 ꢂ
12 ꢂ
24 ꢂ
12 ꢂ
17 ꢂ
36c poor yield could be obtained. It was more interesting that
ꢂ I2–TBHP
80d
the benzyl was removed in the reaction process (Table 3,
ꢂ I2–TBHP–Py ꢂ CH3CN
ꢂ I2–TBHP–Py ꢂ CH3CN
ꢂ I2–TBHP–Py ꢂ CH3CN
81e
entry 4).
90f
We have also attempted to construct new fused
thiazoles and imidazoles by this protocol. Structures
similar to 2-aminopyridine, such as 2-aminobenzi-
midazole and 2-aminobenzothiazole, were chosen as
candidates (Table 3, entries 5 and 6). However, neither
of them took part in the reaction. It was also observed
that 4-aminopyridine does not undergo the Michael
reaction with β-nitrostyrene under the catalytic condi-
tion (Table 3, entry 7). Activated alkene, 2-(2-fluoroben-
zylidene) malononitrile, which was suggested as a
Michael addition acceptor, did not proceed as well in the
reaction (Table 3, entry 8). Thus, this method showed
good selectivity.
66g,c
16f,c
ꢂ I2–TBHP–Py ꢂ Solventless ꢂ 80
h
ꢂ TBHP
ꢂ TBHP
ꢂ I2–Py
ꢂ CH3CN
ꢂ CH3CN
ꢂ CH3CN
ꢂ CH3CN
ꢂ r. t.
ꢂ 80
ꢂ 80
ꢂ 80
ꢂ 80
ꢂ 80
–
h
–
71i
80j
52k
65l
10 ꢂ TBHP–Py
11 ꢂ I2–30 % H2O2ꢂ CH3CN
12 ꢂ KI–TBHP ꢂ CH3CN
aReaction condition: 2-aminopyridine (1.0 mmol), nitroolefin
(1.05 mmol), solvent (10 mL), temperature means the oil bath
temperature; bisolated yields; cI2 (0.2 mmol) was used, and the
materials were not consumed completely; dI2 (0.1 mmol) and TBHP
(2.0mmol) were added; eI2 (0.1 mmol), pyridine (0.62 mmol), and
TBHP (2.0 mmol) were added; fI2 (0.2 mmol), pyridine (0.62 mmol),
and TBHP (2.0 mmol) were added; gI2 (0.2 mmol), pyridine
(0.62 mmol), and TBHP (1.0 mmol) were added; hno reaction, and
TBHP (2.0 mmol) was used; iI2 (0.2 mmol) and pyridine (0.62 mmol)
were added; jTBHP (2.0 mmol) and pyridine (0.62 mmol) were
added; k30 % H2O2 (1 mL) was used; lKI (0.2 mmol) and TBHP
(2.0 mmol) were added.
Based on the above results and previous reports [31,
35, 40], a plausible mechanism is put forward (Scheme 1).
On the one hand, “outer complex” 4 was formed from
pyridine and iodine. In the presence of TBHP, intermedi-
ate 5 was generated, which split into two kinds of radicals,
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ꢁꢀꢀꢀ
L. An et al.: Metal-free oxidative coupling of aminopyridines with nitroolefinsꢃ
ꢃ3
Table 2:ꢀSynthesis of imidazo[1,2-a]pyridines.a
R1
CH3CN
R1
NO2
N
N
2
+
R
I2-TBHP-Py
N
NH2
R2
NO2
ꢂ
ꢂ
ꢂ
N
N
N
N
N
N
N
N
O N
2
O2N
O2
N
O2N
O
O
O
3a, 80 °C, 90 %b ꢂ
3b, 80 °C, 85 % ꢂ
3c, 80 °C, 87 %ꢂ
3d, r. t., 69 %
ꢂ
ꢂ
ꢂ
N
N
N
N
N
N
N
N
F
O N
2
O N
O2N
2
O2N
Br
Cl
Br
3e, r. t., 40 %
ꢂ
ꢂ
3f, r. t., 71 %
ꢂ
ꢂ
3g, r. t., 70 %
ꢂ
ꢂ
3h, r. t., 78 %
N
N
N
N
N
N
N
N
O N
O N
2
2
O N
2
O2N
O
O
O
3i, r. t., 48 %
ꢂ
ꢂ
3j, 100 °C, 46 % ꢂ
3k, r. t., 58 %
ꢂ
ꢂ
3l, 80 °C, 71 %
ꢂ
N
N
N
N
N
N
F
O2N
O2N
O2N
Br
Cl
3m, r. t., 47 %
ꢂ
3n, 100 °C, 46 % ꢂ
3o, r. t., 65 %
ꢂ
aReaction conditions: 2-aminopyridine (1.0 mmol), nitroolefin (1.05 mmol), I2 (0.2 mmol), pyridine (0.62 mmol), and TBHP (2.0 mmol) were
added in CH3CN (10 mL). The reaction time was 12 h. Temperature means the oil bath temperature. bIsolated yields.
6 and 7. The radicals 6 or 7 resulted in PyHI 8 or TBHP
after activating the intermediate 12, which would be illus-
3 Conclusions
trated in the following step. PyHI 8 and HI were oxidized In summary, we have successfully developed a metal-
by TBHP to “outer complex” 4. Thus, the catalytic cycle free catalytic system for the synthesis of 3-nitro-
was achieved.
2-arylimidazo[1,2-a]pyridine derivatives. The component
On the other hand, intermediate 9 was produced in this system shows a synergistic effect for catalysis. It is
from β-nitrostyrene and 2-aminopyridine via Michael simple and environmentally benign.
addition. The intermediate 9 was oxidized to imine 10,
from which enamine 11 equilibrated. The intermediate
12, generated by one-electron oxidation, was abstracted
of hydrogen by radicals 6 or 7 to intermediate 13. After 4 Experimental section
intramolecular nucleophilic addition occurred, the final
product was obtained by proton elimination of interme- All materials were obtained from commercial suppli-
diate 14.
ers and were used without further purification unless
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ꢀꢀꢀꢁ
4ꢀ ꢀL. An et al.: Metal-free oxidative coupling of aminopyridines with nitroolefins
Table 3:ꢀThe trials on extension of scope under the present catalytic
otherwise noted. The nitroolefins were prepared by the
Henry reaction. All solvents were reagent grade. Flash
chromatography was performed with silica gel (200–
300 mesh). The nuclear magnetic resonance (NMR)
spectra were measured on an AVANCE 400 spectrometer
system.
Entryꢁ 1
ꢁ 2
ꢁ Product (yield) ꢁ Temp. (°C)
1
2
3
4
5
6
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ Complex mixtureꢂ 80
O2
N
O
N
N
N
NH
1
at 400 MHz for H and 100 MHz for 13C in CDCl3 solution
2
NO
NO
NO
NO
NO
NO
2 ꢂ Complex mixtureꢂ 100
with trimethylsilyl as an internal standard. Chemical
shifts (δ) are given in parts per million and coupling con-
stants (J) in Hertz. High-resolution mass spectroscopy
(HRMS) spectra were recorded on an LTQ-Orbitrap mass
spectrometer [(+)-ESI].
ꢂ
ꢂ
ꢂ
ꢂ
NH
2
2 ꢂ No reaction
2 ꢂ 3a (20 %)
ꢂ 100
ꢂ 100
ꢂ 100
ꢂ 100
ꢂ 100
NHAc
N
NHBn
S
2 ꢂ No reaction
2 ꢂ No reaction
2 ꢂ No reaction
SH
N
4.1 General procedure for the synthesis
N
of imidazo[1,2-a]pyridine derivatives
NH
2 ꢂ
N
H
In
a 50-mL round-bottomed flask, a mixture of
NH2
7
8
ꢂ
ꢂ
ꢂ
ꢂ
2-aminopyridine (1 mmol) and nitroolefin (1.05 mmol)
was stirred in 10 mL acetonitrile. Then, I2 (0.2 mmol),
TBHP (2 mmol), and pyridine (0.05 mL) were added to the
above mixture, and the resulting mixture was allowed to
stir under reflux or at room temperature for the specified
time (Table 2). The progress of the reaction was monitored
by thin-layer chromatography (TLC). After the completion
of the reaction, the reaction mixture was cooled to room
temperature and poured into saturated sodium bisulfite
N
F
CN
ꢂ No reaction
ꢂ 100
N
NH
2
CN
aReaction conditions: 2-aminopyridine (1.0 mmol), nitroolefin
(1.05 mmol), I2 (0.2 mmol), pyridine (0.62 mmol), TBHP (2.0 mmol),
and CH3CN (10 mL). Temperature means the oil bath temperature.
The reaction time was 12 h. bIsolated yields.
TBHP
PyI•
6
7
(PyI+)I−
PyIOOtBu
+
I2 + Py
tBuOO•
5
4
HI
H•
PyHI
8
+
TBHP
Michael
addition
[O]
NO2
NH
N
N
N
NO2
NO2
+
N
NH2
2a
1a
9
10
tBuOO•
PyI•
or
+
NH
[O]
N
N
N
N
NH
NO2
− e
NO2
NO2
PyHI or TBHP
11
12
13
N
− H+
NH
N
N
O2N
O2N
14
Scheme 1:ꢀProposed mechanism.
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ꢁꢀꢀꢀ
ꢃ5
L. An et al.: Metal-free oxidative coupling of aminopyridines with nitroolefinsꢃ
solution (15 mL). After sonication for 10 min, the mixture 4.1.5 2-(2-Fluorophenyl)-3-nitroimidazo[1,2-a]pyridine
was extracted with ethyl acetate (3 ꢀ×ꢀ 15 mL), followed by
(3e)
drying with anhydrous MgSO4. After evaporation of the
solvent, the residue was purified by flash chromatography 1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.47 (d, J ꢀ=ꢀ 7.0 Hz, 1H), 7.85
to afford the desired product.
(d, J ꢀ=ꢀ 8.9 Hz, 1H), 7.63–7.70 (m, 2H), 7.48–7.53 (m, 1H),
7.28–7.32 (m, 2H), 7.21 (t, J ꢀ=ꢀ 9.2 Hz, 1H) ppm. – 13C NMR
(100 MHz, CDCl3): δ ꢀ=ꢀ 161.8, 159.3, 145.2, 144.3, 131.9, 131.8,
131.1, 131.1, 130.7, 127.8, 124.2, 124.2, 121.0, 120.8, 118.4, 116.7,
115.9, 115.7 ppm. – HRMS [(+)-ESI]: m/z ꢀ=ꢀ 280.0496 (calcd.
4.1.1 3-Nitro-2-phenylimidazo[1,2-a]pyridine (3a) [35]
+
280.0498 for C13H8FN3O2Na, [M+Na] ).
1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.53 (d, J ꢀ=ꢀ 6.9 Hz, 1H),
7.91–7.92 (m, 2H), 7.86 (d, J ꢀ=ꢀ 8 Hz, 1H), 7.67 (t, J ꢀ=ꢀ 7.9 Hz,
1H), 7.52–7.53 (m, 3H), 7.28–7.32 (m, 1H) ppm. – 13C NMR
(100 MHz, CDCl3): δ ꢀ=ꢀ 150.3, 145.2, 131.9, 130.8, 130.2, 130.1,
128.2, 128.2, 118.3, 116.5. – HRMS [(+)-ESI]: m/z ꢀ=ꢀ 240.0776
4.1.6 2-(3-Bromophenyl)-3-nitroimidazo[1,2-a]pyridine
(3f) [31]
+
(calcd. 240.0773 for C13H10N3O2, [M+H] ).
1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.42 (d, J ꢀ=ꢀ 7.2 Hz, 1H),
8.01 (s, 1H), 7.81 (t, J ꢀ=ꢀ 8.4 Hz, 2H), 7.57–7.66 (m, 2H), 7.24–
7.35(m, 2H) ppm. – 13C NMR (100 MHz, CDCl3): δ ꢀ=ꢀ 148.2,
145.0, 133.9, 133.0, 132.8, 131.1, 129.6, 128.8, 128.0, 122.0,
118.3, 116.8 ppm. – HRMS [(+)-ESI]: m/z ꢀ=ꢀ 339.9702 (calcd.
4.1.2 2-(4-Methoxyphenyl)-3-nitroimidazo[1,2-a]
pyridine (3b) [31]
+
339.9698 for C13H8BrN3O2Na, [M+Na] ).
1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.50 (d, J ꢀ=ꢀ 6.8 Hz, 1H),
7.95 (d, J ꢀ=ꢀ 8.5 Hz, 2H), 7.81 (d, J ꢀ=ꢀ 8.8 Hz, 1H), 7.64 (t, J ꢀ=ꢀ
8 Hz, 1H), 7.24 (d, J ꢀ=ꢀ 6.8 Hz, 1H), 7.02 (d, J ꢀ=ꢀ 8.5 Hz, 2H), 4.1.7 2-(4-Bromophenyl)-3-nitroimidazo[1,2-a]pyridine
3.89 (s, 3H) ppm. – HRMS [(+)-ESI]: m/z ꢀ=ꢀ 270.0871 (calcd.
(3g) [41]
+
270.0879 for C14H12N3O3, [M+H] ).
1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.5 (d, J ꢀ=ꢀ 7.2 Hz, 1H),
7.80–7.85 (m, 3H), 7.63–7.69 (m, 3H), 7.27–7.32 (m, 1H) ppm.
–
13C NMR (100 MHz, CDCl3): δ ꢀ=ꢀ 149.1, 145.2, 131.7, 131.4,
4.1.3 3-Nitro-2-p-tolylimidazo[1,2-a]pyridine (3c) [35]
131.1, 130.8, 128.2, 124.9, 118.4, 116.7 ppm. – HRMS [(+)-
ESI]: m/z ꢀ=ꢀ 339.9695 (calcd. 339.9698 for C13H8BrN3O2Na,
1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.51 (d, J ꢀ=ꢀ 6.9 Hz, 1H),
7.83 (d, J ꢀ=ꢀ 8.0 Hz, 3H), 7.64 (t, J ꢀ=ꢀ 7.9 Hz, 1H), 7.31 (d, J ꢀ=ꢀ
8 Hz, 2H), 7.22–7.27 (m, 1H), 2.44 (s, 3H) ppm. – 13C NMR
(100 MHz, CDCl3): δ ꢀ=ꢀ 150.4, 145.2, 140.5, 130.7, 130.0,
129.0, 128.9, 128.2, 118.2, 116.3, 21.5 ppm. – HRMS [(+)-
ESI]: m/z ꢀ=ꢀ 276.0740 (calcd. 276.0749 for C14H11N3O2Na,
+
[M+Na] ).
4.1.8 2-(4-Chlorophenyl)-3-nitroimidazo[1,2-a]pyridine
(3h) [31]
+
[M+Na] ).
1H NMR (400 MHz, DMSO): δ ꢀ=ꢀ 9.42 (d, J ꢀ=ꢀ 6.8 Hz, 1H), 7.97
(d, J ꢀ=ꢀ 8.8, 1H), 7.82–7.88 (m, 3H), 7.59 (d, J ꢀ=ꢀ 8 Hz, 2H),
7.49 (t, J ꢀ=ꢀ 7.2 Hz, 1H). – 13C NMR (100 MHz, DMSO): δ ꢀ=ꢀ
148.3, 145.2, 135.1, 132.4, 132.2, 131.6, 128.9, 128.5, 118.3,
117.7. – HRMS [(+)-ESI]: m/z ꢀ=ꢀ 274.0387 (calcd. 274.0383 for
4.1.4 2-(Benzo[d][1, 3]dioxol-5-yl)-3-nitroimidazo[1,2-a]
pyridine (3d) [41]
+
C13H9ClN3O2, [M+H] ).
1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.50 (d, J ꢀ=ꢀ 6.8 Hz, 1H),
7.80 (d, J ꢀ=ꢀ 8.9 Hz, 1H), 7.64 (t, J ꢀ=ꢀ 7.9 Hz, 1H), 7.52 (dd,
J ꢀ=ꢀ 8.1, 1.4 Hz, 1H), 7.43 (d, J ꢀ=ꢀ 1.2 Hz, 1H), 7.24–7.27 (m, 4.1.9 8-Methyl-3-nitro-2-phenylimidazo[1,2-a]pyridine
1H), 6.93 (d, J ꢀ=ꢀ 8.1 Hz, 1H), 6.05 (s, 1H) ppm. – 13C NMR
(100 MHz, CDCl3): δ ꢀ=ꢀ 150.0, 149.5, 147.5, 145.1, 131.0, 128.3,
(3i) [31]
125.5, 125.1, 118.2, 116.3, 110.5, 108.2, 101.5 ppm. – HRMS 1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.35 (d, J ꢀ=ꢀ 6.8 Hz, 1H), 7.91
[(+)-ESI]: m/z ꢀ=ꢀ 284.0670 (calcd. 284.0671 for C14H10N3O4, (d, J ꢀ=ꢀ 3.6 Hz, 2H), 7.48–7.50 (m, 3H), 7.43 (d, J ꢀ=ꢀ 6.8 Hz,
+
[M+H] ).
1H),7.16 (t, J ꢀ=ꢀ 8 Hz, 1H), 2.73 (s, 3H) ppm. – 13C NMR
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(100 MHz, CDCl3): δ ꢀ=ꢀ 149.7, 145.2, 132.3, 130.1, 130.0, 129.9, 4.1.14 2-(4-Bromophenyl)-8-methyl-3-
128.7, 128.1, 125.9, 116.5, 77.4, 77.1, 76.7, 16.6 ppm. – HRMS
nitroimidazo[1,2-a]pyridine (3n)
[(+)-ESI]: m/z ꢀ=ꢀ 254.0933 (calcd. 254.0930 for C14H12N3O2,
+
[M+H] ).
1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.37 (d, J ꢀ=ꢀ 6.9 Hz, 1H), 7.82
(d, J ꢀ=ꢀ 8.4 Hz, 1H), 7.65 (d, J ꢀ=ꢀ 8.4 Hz, 1H), 7.47 (d, J ꢀ=ꢀ 7.0
Hz, 1H), 7.20 (t, J ꢀ=ꢀ 7.0 Hz, 1H), 2.73 (s, 2H) ppm. – 13C NMR
(100 MHz, CDCl3): δ ꢀ=ꢀ 148.5, 145.2, 131.8, 131.4, 131.1, 130.1,
128.7, 125.9, 124.6, 116.7, 16.6 ppm. – HRMS [(+)-ESI]: m/z ꢀ=ꢀ
4.1.10 2-(4-Methoxyphenyl)-8-methyl-3-
nitroimidazo[1,2-a]pyridine (3j)
+
332.0016 (calcd. 332.0029 for C14H11BrN3O2, [M+H] ).
1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.32 (d, J ꢀ=ꢀ 6.0 Hz, 1H),
7.94 (d, J ꢀ=ꢀ 8.6 Hz, 2H), 7.40 (d, J ꢀ=ꢀ 6.9 Hz, 1H), 7.11 (t, J ꢀ=ꢀ
6.9 Hz, 1H), 7.00 (d, J ꢀ=ꢀ 8.4 Hz, 2H), 3.87 (s, 3H), 2.69 (s,
3H) ppm. – 13C NMR (100 MHz, CDCl3): δ ꢀ=ꢀ 161.22, 149.59,
145.21, 131.89, 129.85, 128.32, 125.97, 124.48, 116.11, 113.59,
55.37, 16.52 ppm. – HRMS [(+)-ESI]: m/z ꢀ=ꢀ 306.0857 (calcd.
4.1.15 2-(4-Chlorophenyl)-8-methyl-3-
nitroimidazo[1,2-a]pyridine (3o)
1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.36 (d, J ꢀ=ꢀ 6.9 Hz, 1H),
7.88 (d, J ꢀ=ꢀ 8.4 Hz, 2H), 7.47 (t, J ꢀ=ꢀ 7.2 Hz, 3H), 7.19 (t, J ꢀ=ꢀ
7.0 Hz, 1H), 2.72 (s, 3H) ppm. – 13C NMR (100 MHz, CDCl3):
δ ꢀ=ꢀ 148.5, 145.2, 136.2, 131.6, 130.7, 130.1, 128.7, 128.4, 125.9,
116.7, 16.6 ppm. – HRMS [(+)-ESI]: m/z ꢀ=ꢀ 288.0530 (calcd.
+
306.0855 for C15H13N3O3Na, [M+Na] ).
4.1.11 8-Methyl-3-nitro-2-p-tolylimidazo[1,2-a]pyridine
(3k) [31]
+
288.0540 for C14H11ClN3O2, [M+H] ).
1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.33 (d, J ꢀ=ꢀ 6.9 Hz, 1H),
7.83 (d, J ꢀ=ꢀ 7.9 Hz, 2H), 7.40 (d, J ꢀ=ꢀ 7.0 Hz, 1H), 7.30 (d, J ꢀ=ꢀ
7.8 Hz, 2H), 7.13 (t, J ꢀ=ꢀ 7.0 Hz, 1H), 2.70 (s, 3H), 2.43 (s, 3H)
ppm. – 13C NMR (100 MHz, CDCl3): δ ꢀ=ꢀ 149.8, 145.2, 140.3,
130.1, 129.8, 129.3, 128.8, 128.5, 125.9, 116.3, 21.5, 16.6 ppm.
– HRMS [(+)-ESI]: m/z ꢀ=ꢀ 268.1082 (calcd. 268.1086 for
5 Supporting Information
General experimental information, spectroscopic data,
and spectra of compounds 3a–3o are summarized as
Supporting Information available online (DOI: 10.1515/
znb-2015-0171).
+
C15H14N3O2, [M+H] ).
4.1.12 2-(Benzo[d][1,3]dioxol-5-yl)-8-methyl-3-
nitroimidazo[1,2-a]pyridine (3l)
Acknowledgments: We are grateful to the National
Natural Science Foundation of China (21375044), Uni-
versity Natural Science Foundation of Jiangsu Province
(12KJD150002), and Administration of Science & Technol-
ogy of Huaian City (HAG2013011) for financial support.
1H NMR (400 MHz, CDCl3): δ ꢀ=ꢀ 9.35 (d, J ꢀ=ꢀ 6.9 Hz, 1H), 7.51–
7.58 (dd, J ꢀ=ꢀ 6,4 Hz, 1.6 Hz, 1H), 7.43(d, J ꢀ=ꢀ 1.6 Hz, 2H), 7.15
(t, J ꢀ=ꢀ 7.1 Hz, 1H), 6.93 (d, J ꢀ=ꢀ 8.1 Hz, 1H), 6.04 (s, 1H), 2.71
(s, 3H) ppm. – 13C NMR (100 MHz, CDCl3): δ ꢀ=ꢀ 149.4, 149.3,
147.5, 145.1, 129.9, 128.4, 125.9, 125.1, 116.3, 110.6, 108.2,
101.5, 16.6 ppm. – HRMS [(+)-ESI]: m/z ꢀ=ꢀ 320.0626 (calcd.
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Z. Naturforsch.ꢃ
ꢃ2016 | Volume x | Issue x(b)
Graphical synopsis
Litao An, Xiaojun Sun, Meng Lv,
Jianfeng Zhou, Fengxia Zhu and
Hui Zhong
Metal-free oxidative coupling of
aminopyridines with nitroolefins to
imidazo[1,2-a]pyridine in the presence
of I2–TBHP–pyridine
DOI 10.1515/znb-2015-0171
Z. Naturforsch. 2016; x(x)b: xxx–xxx
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