Cu(I)-catalyzed synthesis of imidazo[1,2-a]pyridines from aminopyridines and nitroolefins using air as the oxidant

Article abstract of DOI:10.1021/jo202447p

A copper-catalyzed method for the synthesis of imidazo[1,2-a]pyridines with aminopyridines and nitroolefins using air as oxidation agent in a one-pot procedure has been developed. In this process, the reaction appears to be very general and suitable for c

Full text of DOI:10.1021/jo202447p

Note
pubs.acs.org/joc
Cu(I)-Catalyzed Synthesis of Imidazo[1,2-a]pyridines from
Aminopyridines and Nitroolefins Using Air as the Oxidant
Ru-Long Yan,* Hao Yan, Chao Ma, Zhi-Yong Ren, Xi-Ai Gao, Guo-Sheng Huang,* and Yong-Min Liang
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Key Laboratory of Nonferrous Metal Chemistry and
Resources Utilization of Gansu Province, Lanzhou 730000, P. R. of China
S
* Supporting Information
ABSTRACT: A copper-catalyzed method for the synthesis of
imidazo[1,2-a]pyridines with aminopyridines and nitroolefins
using air as oxidation agent in a one-pot procedure has been
developed. In this process, the reaction appears to be very
general and suitable for construction of a variety of
imidazo[1,2-a]pyridines.
he imidazo[1,2-a]pyridine core is one of the most
important heterocycles since it has not only found
60 °C (Table 1, entries 3 and 4). Furthermore, when the
copper salts were changed to CuBr, CuCl, CuOTf, Cu(OAc)2,
and Cu(OTf)2, CuBr showed the highest activity for this
reaction and resulted in 90% yield (Table 1, entries 5−9).
Other solvents such as DMSO, NMP, CH3CN, and CH3OH
were also evaluated, and no better result was obtained (Table 1,
entries 11−14). In addition, in a control reaction with no metal
salts as catalyst, no target product was obtained (Table 1, entry
10).
Under the optimized reaction conditions, we examined a
series of aminopyridines and nitroolefins to establish the scope
and limitations of this process. Generally, the reaction of
aminopyridines and nitroolefins proceeded smoothly and
afforded the corresponding imidazo[1,2-a] 3 with great
efficiency (Table 2). To our delight, a wide range substituted
groups of nitroolefins or aminopyridines all gave the desired
products in good yields, which include methyl, methoxyl, ester,
naphthyl, piperonyl, bromo, or chloro groups. For the
electronic effects of these reactions, we found the electron-
rich nitroolefins or aminopyridines show better reactivity and
gave higher yields than electron-deficient ones. Further
investigations demonstrated that the steric hindrance of the
substitutes on the pyridine rings can affect the yields, the
substrates 1a and 1d reacted with 2e and 2a to form the
products 3ae and 3da in 68% and 49%, respectively (Table 2,
entries 5 and 20). Moreover, heteroaryl species such as furanyl
also underwent the desired reaction to give the corresponding
product in 38% yield (Table 2, entry 14).
T
widespread applications in medicinal chemistry and drug
synthesis1 but because it is also broadly used in material
science.2 Consequently, it has attracted considerable interest for
synthetic chemists and stimulated the development of
numerous methods for their preparation.3 Recently, several
new approaches based on dehydrogenation through C−H
activation catalyzed by transition metals4 and tetrabutylammo-
nium iodide (TBAI)-catalyzed oxidative coupling5 have been
developed for the construction of imidazo[1,2-a]pyridines.
However, there are very few general methods that convert
commercially available or readily accessible materials in one
step to polysubstituted imidazo[1,2-a]pyridines. Thus, there is
still a need for direct and efficient methods to afford
functionalized imidazo[1,2-a]pyridines.
In accordance with the ideology of green chemistry,6 air is
the ideal oxidant because of its abundance, low cost, and lack of
toxic byproduct.7 With the development of C−H activation, air
has attracted much attention because it is safe and cheap in
industrial applications.8 Therefore, using air as the oxidant to
construct heterocycles with simple and readily accessible
substrates is a challenging area. As part of our continuing
study on the utilization of oxygen in organic chemistry,9 we
report here a facile and efficient method to synthesize
polysubstituted imidazo[1,2-a]pyridines using air as the
oxidant.
At the beginning of our study, pyridin-2-amine (1a) and (E)-
(2-nitrovinyl)benzene (2a) were chosen as test substrates for
this cyclization using CuI in DMF under air at 80 °C to achieve
the transformation. Gratifyingly, the desired 3-nitro-2-
phenylimidazo[1,2-a]pyridine (3aa) was obtained in 88%
yield after 4 h (Table 1, entry 1). It is worth mentioning that
we confirmed the structure of 3ba unambiguously through an
X-ray crystal analysis.10 When O2 was employed as the oxidant,
only 84% of 3aa was isolated (Table 1, entry 2). Thus, air was
chosen as oxidant for its abundance, low cost, and convenience.
The yield decreased when the temperature changed to 110 or
On the basis of the results obtained above, a plausible
mechanism of this reaction is illustrated in Scheme 1.The
reaction may undergo the following steps. The first step
involves a coupling of the substrates 1 and 2 to produce the
Michael addition intermediate 4. A one-electron oxidation of
intermediate 4 with copper catalyst generates radical cation 5,
which is followed by hydrogen abstraction with oxidation
Received: December 1, 2011
Published: January 12, 2012
© 2012 American Chemical Society
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Note
a
Table 1. Optimization of the Reaction Conditions
entry
1
catalyst
CuI
oxidant
solvent
temp (°C)
yield (%)
air
O2
air
air
air
air
air
air
air
air
air
air
air
air
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
NMP
CH3CN
CH3OH
80
80
110
60
80
80
80
80
80
80
80
80
80
80
88
84
85
73
90
81
72
79
86
0
b
2
CuI
3
CuI
4
CuI
5
CuBr
6
CuCl
7
Cu(OTf)2
Cu(OAc)2
CuOTf
8
9
10
11
12
13
14
CuBr
CuBr
CuBr
CuBr
87
83
48
53
a
b
Reaction conditions: 1a (0.30 mmol), 2a (0.36 mmol), catalysts (0.03 mmol), 2 mL of solvent, in an open tube, 4 h. O2 (1 atm).
a
Table 2. Synthesis of Imidazo[1,2-a]pyridines from Aminopyridines and Nitroolefins
entry
R1
R2
product
yield (%)
1
2
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1c
1d
1e
1f
H
2a
2b
2c
2d
2e
2f
Ph
3aa
3ab
3ac
3ad
3ae
3af
90
95
84
81
68
86
80
86
70
88
66
92
65
38
94
70
72
76
86
49
61
56
H
3-Me-Ph
4-Me-Ph
3,4-diMe-Ph
2-MeO-Ph
4-MeO-Ph
2-Cl-Ph
3-Cl-Ph
4-Cl-Ph
3-Br-Ph
4-Br-Ph
1-naphthyl
piperonyl
2-furyl
3
H
4
H
5
H
6
H
7
H
2g
2h
2i
3ag
3ah
3ai
8
H
9
H
10
11
12
13
14
15
16
17
18
19
20
21
22
H
2j
3aj
H
2k
2l
3ak
3al
H
H
2m
2n
2a
2b
2j
3am
3an
3ba
3bb
3bj
3bc
3ca
3da
3ea
3fa
H
3-Me
3-Me
3-Me
3-Me
5-Me
6-Me
5-Cl
4-COOEt
Ph
3-Me-Ph
3-Br-Ph
4-Me-Ph
Ph
2c
2a
2a
2a
2a
Ph
Ph
Ph
a
Reaction conditions: 1 (0.3 mmol), 2 (0.36 mmol), CuBr (0.03 mmol), 2 mL DMF, in an open tube, 80 °C, 4 h.
resulting in the formation of nitrenium ion 6.11 The imine 7 is
then formed by proton elimination and equilibrates to enamine
8. Similarly, intermediate 9, produced by one-electron oxidation
with copper catalyst from enamine 8, generates the nitrenium
ion 10 by hydride abstraction with oxidation. Finally,
intermediate 10 undergoes intramolecular nucleophilic addition
to give intermediate 11 and the subsequent proton elimination
to afford product 3.
In conclusion, we have developed a direct Cu(I)-catalyzed
method for the synthesis of imidazo[1,2-a]pyridines with
aminopyridines and nitroolefins in a one-pot manner under air.
Various substitutes are tolerated in this reaction, which
proceeds smoothly in moderate to good yields. The procedure,
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Note
Scheme 1. Plausible Reaction Mechanism
H), 7.50−7.46 (m, 1 H), 7.27−7.24 (m, 1 H), 7.12−7.08 (t, J = 7.6
Hz, 1 H), 7.03−7.01 (d, J = 8.4, 1 H), 3.82 (s, 3 H); 13C NMR (100
MHz, CDCl3) δ 157.5, 146.9, 145.0, 131.3, 130.5, 130.1, 127.5, 121.8,
120.5, 118.1, 116.1, 110.8, 55.5; IR (neat, cm−1) 3068, 3037, 2926,
1631, 1537, 1438, 1368, 1216, 758; HRMS calcd for C14H12N3O3 [M
+ H]+ 270.0873, found 270.0878.
2-(4-Methoxyphenyl)-3-nitroimidazo[1,2-a]pyridine 3af: yel-
low solid; mp 168−170 °C; 1H NMR (400 MHz, CDCl3) δ 9.52−9.50
(d, J = 7.2 Hz, 1 H), 7.95−7.93 (d, J = 8.8 Hz, 2 H), 7.81−7.79 (d, J =
8.8 Hz, 1 H), 7.65−7.62 (t, 1 H), 7.25−7.23 (d, J = 6.8 Hz, 1 H),
7.03−7.01 (d, J = 8.8 Hz, 2 H), 3.89 (s, 3 H); 13C NMR (100 MHz,
CDCl3) δ 161.3,150.2, 145.2, 131.8, 130.8, 128.3, 124.0, 118.0, 116.1,
113.6, 55.3; IR (neat, cm−1) 3090, 3016, 2940, 1633, 1540, 1444, 1368,
1210, 961, 760, 705; HRMS calcd for C14H12N3O3 [M + H]+
270.0873, found 270.0874.
using air as oxidative agent, is a simple, economical, and
environmentally friendly protocol for the synthesis of imidazo-
[1,2-a]pyridines.
EXPERIMENTAL SECTION
■
Typical Procedure for the Preparation of Imidazo[1,2-
a]pyridines 3. A tube was charged with 1 (0.30 mmol), 2 (0.36
mmol), and CuBr (4.3 mg, 0.03 mmol). Then 2 mL of DMF was
added to the reaction system. The reaction mixture was stirred at 80
°C under air for 4 h. After the mixture was cooled to room
temperature, the solvent was diluted with 10 mL of ethyl acetate,
washed with 5 mL of brine, and dried over anhydrous Na2SO4. After
the solvent was evaporated in vacuo, the residues were purified by
column chromatography, eluting with petroleum ether/EtOAc to
afford pure 3.
2-(2-Chlorophenyl)-3-nitroimidazo[1,2-a]pyridine 3ag: yel-
1
3-Nitro-2-phenylimidazo[1,2-a]pyridine 3aa: yellow solid; mp
low viscous oil; H NMR (400 MHz, CDCl3) δ 9.52−9.50 (d, J =
1
172−174 °C; H NMR (400 MHz, CDCl3): δ 9.52−9.50 (d, J = 7.2
7.2 Hz, 1 H), 7.88−7.86 (d, J = 8.8 Hz, 1 H), 7.70−7.66 (m, 1 H),
7.55−7.52 (m, 2 H), 7.47−7.31 (m, 3 H); 13C NMR (100 MHz,
CDCl3) δ 147.3, 144.9, 133.9, 131.9, 130.8, 130.7, 130.6, 129.5, 127.7,
126.7, 118.5, 116.7; IR (neat, cm−1) 3053, 1672, 1632, 1539, 1369,
763, 732; HRMS calcd for C13H9ClN3O2 [M + H]+ 274.0378, found
274.0383.
Hz, 1 H), 7.92−7.89 (m, 2 H),7.85 −7.83 (d, J = 9.2 Hz, 1 H),7.67−
7.63 (m, 1 H), 7.51−7.50 (t, J = 3.2 Hz, 3 H), 7.29−7.26 (q, 1 H); 13C
NMR (100 MHz, CDCl3): δ 150.2, 145.1, 131.8, 130.8, 130.1, 130.0,
128.16, 128.12, 118.3, 116.4; IR (neat, cm−1) 3061, 3034, 1630, 1531,
+
1367, 923, 759, 693; HRMS calcd for C13H10N3O2 [M + H]
240.0768, found 240.0761.
2-(3-Chlorophenyl)-3-nitroimidazo[1,2-a]pyridine 3ah: yel-
3-Nitro-2-m-tolylimidazo[1,2-a]pyridine 3ab: yellow solid; mp
1
low solid; mp 180−182 °C; H NMR (400 MHz, CDCl3) δ 9.52−
1
140−142 °C; H NMR (400 MHz, CDCl3) δ 9.49−9.47 (t, 1 H),
9.50 (d, J = 7.2 Hz, 1 H), 7.91−7.79 (m, 3 H), 7.70−7.66 (m, 1 H),
7.50−7.42 (m, 2 H), 7.33−7.29 (m, 1 H); 13C NMR (100 MHz,
CDCl3) δ 148.5, 145.0, 134.0, 133.5, 131.0, 130.1, 130.0, 129.3, 128.2,
128.0, 118.3, 116.7; IR (neat, cm−1) 3030, 1631, 1529, 1477, 1366,
787, 746; HRMS calcd for C13H9ClN3O2 [M + H]+ 274.0378, found
274.0382.
7.83−7.80 (q, 1 H), 7.70−7.69 (d, J = 6.8 Hz, 2 H), 7.65−7.61 (t, 1
H), 7.40−7.36 (t, J = 8 Hz, 1 H), 7.32−7.30 (d, J = 7.6 Hz, 1 H),
7.27−7.23 (t, 1 H), 2.44 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ
150.3, 145.0, 137.7, 131.7, 130.9, 130.7, 130.3, 128.0, 127.9, 127.1,
118.1, 116.3, 21.3; IR (neat, cm−1) 3061, 3030, 2920, 1632, 1528,
1432, 1369, 751, 689; HRMS calcd for C14H12N3O2 [M + H]+
254.0924, found 254.0932.
2-(4-Chlorophenyl)-3-nitroimidazo[1,2-a]pyridine 3ai: yellow
solid; mp 184−186 °C; 1H NMR (400 MHz, CDCl3): δ 9.52−9.50 (d,
J = 6.8 Hz, 1H),7.89−7.83 (m, 3 H), 7.69−7.65 (m, 1 H), 7.49−7.47
(d, J = 8.8 Hz, 2 H), 7.31−7.28 (m, 1 H); 13C NMR (100 MHz,
CDCl3): δ 149.0, 145.1, 136.4, 131.4, 131.0, 130.2, 128.4, 128.1, 118.3,
116.6; IR (neat, cm−1) 3059, 3026, 1632, 1530, 1336, 861, 828; HRMS
calcd for C13H9ClN3O2 [M + H]+ 274.0378, found 274.0380 .
2-(3-Bromophenyl)-3-nitroimidazo[1,2-a]pyridine 3aj: yellow
solid; mp 138−140 °C; 1H NMR (400 MHz, CDCl3) δ 9.51−9.50 (d,
J = 6.8 Hz, 1 H), 8.06−8.05 (t, 1 H), 7.86−7.84 (d, J = 8.4 Hz, 2 H),
7.70−7.62 (m, 2 H), 7.39−7.35 (t, J = 8 Hz, 1 H), 7.33−7.29 (m, 1
H); 13C NMR (100 MHz, CDCl3): δ 148.4, 145.0, 133.8, 133.1, 132.8,
131.0, 129.6, 128.7, 128.1, 122.1, 118.4, 116.7; IR (neat, cm−1) 3031,
1630, 1529, 1371, 747, 723; HRMS calcd for C13H9BrN3O2 [M + H]+
317.9873, found 317.9876.
3-Nitro-2-p-tolylimidazo[1,2-a]pyridine 3ac: yellow solid; mp
1
204−206 °C; H NMR (400 MHz, CDCl3) δ 9.52−9.50 (d, J = 7.2
Hz, 1 H), 7.95−7.93 (d, J = 8.8 Hz, 2 H), 7.81−7.79 (d, J = 8.8 Hz, 1
H), 7.65−7.62 (t, 1 H), 7.25−7.23 (d, J = 6.8 Hz, 1 H), 7.03−7.01 (d,
J = 8.8 Hz, 2 H), 3.89 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 150.4,
145.1, 140.4, 130.7, 129.9, 128.9, 128.8, 128.1, 118.1, 116.2, 21.5; IR
(neat, cm−1) 3058, 3026, 2917, 1674, 1537, 1475, 1362, 1362, 750;
HRMS calcd for C14H12N3O2 [M + H]+ 254.0924, found 254.0921.
2-(3,4-Dimethylphenyl)-3-nitroimidazo[1,2-a]pyridine 3ad:
yellow solid; mp 146−148 °C; 1H NMR (400 MHz, CDCl3) δ
9.52−9.50 (d, J = 6.8 Hz, 1 H), 7.84−7.81 (d, J = 9.2 Hz, 1 H), 7.69−
7.62 (m, 3 H), 7.28−7.24 (d, 2 H), 2.35 (s, 6 H); 13C NMR (100
MHz, CDCl3) δ 150.6, 145.1, 139.2, 136.5, 130.9, 130.7, 129.4, 129.2,
128.2, 127.5, 118.2, 116.2, 19.8, 19.7; IR (neat, cm−1) 3064, 3031,
2916, 1628, 1534, 1478, 1374, 883; HRMS calcd for C15H14N3O2 [M
+ H]+ 268.1081, found 268.1084.
2-(4-Bromophenyl)-3-nitroimidazo[1,2-a]pyridine 3ak: yel-
1
low solid; mp 186−188 °C; H NMR (400 MHz, CDCl3) δ 9.52−
9.50 (d, J = 6.8 Hz, 1 H), 7.85−7.79 (m, 3 H), 7.69−7.63 (m, 3 H),
7.32−7.28 (m, 1 H); 13C NMR (100 MHz, CDCl3) δ 149.0, 145.1,
131.6, 131.3, 131.0, 130.7, 128.1, 124.8, 118.3, 116.6; IR (neat, cm−1)
2-(2-Methoxyphenyl)-3-nitroimidazo[1,2-a]pyridine 3ae: yel-
low solid; mp 200−202 °C; 1H NMR (400 MHz, CDCl3) δ 9.48−9.47
(d, J = 6.8 Hz, 1 H), 7.84−7.82 (d, J = 8.8 Hz, 1 H), 7.64−7.57 (m, 2
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Note
3029, 1630, 1594, 1530, 1370, 861, 827; HRMS calcd for
C13H9BrN3O2 [M + H]+ 317.9873, found 317.9876.
3054, 3025, 2919, 1651, 1527, 1481, 1353, 1218, 1199, 739, 693;
HRMS calcd for C14H12N3O2 [M + H]+ 254.0924, found 254.0920.
5-Methyl-3-nitro-2-phenylimidazo[1,2-a]pyridine 3da: yellow
2-(Naphthalen-2-yl)-3-nitroimidazo[1,2-a]pyridine 3al: yel-
1
1
viscous oil; H NMR (400 MHz, CDCl3) δ 8.01−7.98 (t, 2 H), 7.74
low solid; mp 118−120 °C; H NMR (400 MHz, CDCl3) δ 9.57−
(s, 1 H), 7.56−7.54 (d, J = 8.8 Hz, 1 H), 7.46−7.42 (t, 2 H), 7.34−
7.31 (t, J = 7.2 Hz, 1 H), 7.16−7.12 (q, 1 H), 6.62−6.60 (d, J = 6.8 Hz,
1 H), 2.61 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 146.1, 145.7,
134.3, 133.9, 128.6, 127.8, 126.0, 124.8, 114.9, 111.5, 18.7; IR (neat,
cm−1) 3064, 3033, 2921, 1679, 1547, 1479, 1273, 1154, 776, 742;
HRMS calcd for C14H12N3O2 [M + H]+ 254.0924, found 254.0928.
6-Chloro-3-nitro-2-phenylimidazo[1,2-a]pyridine 3ea: yellow
solid; mp 142−144 °C; 1H NMR (400 MHz, CDCl3) δ 9.56−9.55 (q,
1 H), 7.89−7.86 (m, 2 H), 7.77−7.75 (q, 1 H), 7.62−7.59 (d d, J =
9.2, 2 Hz, 1 H), 7.51−7.49 (q, 3 H); 13C NMR (100 MHz, CDCl3) δ
150.3, 143.3, 131.9, 131.4, 130.3, 129.9, 128.1, 126.0, 124.9,118.5; IR
(neat, cm−1) 3052, 3019, 1654, 1529, 1480, 1365, 738, 697; HRMS
calcd for C13H9ClN3O2 [M + H]+ 274.0378, found 274.0373.
9.55 (d, J = 7.2 Hz, 1 H), 8.01−7.99 (d, J = 8 Hz, 1 H), 7.94−7.92 (d,
J = 8 Hz, 1 H), 7.89−7.87 (d, J = 9.2 Hz, 1 H), 7.71−7.65 (m, 3 H),
7.61−7.57 (t, 1 H), 7.53−7.49 (m,1 H), 7.46−7.42 (m,1 H), 7.33−
7.29 (m,1 H); 13C NMR (100 MHz, CDCl3) δ 149.3, 145.2, 133.3,
131.1, 130.8, 130.2, 129.9, 128.5, 128.2, 127.9, 126.8, 126.0, 124.9,
124.8, 118.4, 116.6; IR (neat, cm−1) 3052, 1630, 1532, 1481, 1364,
775, 743; HRMS calcd for C17H12N3O2 [M + H]+ 290.0924, found
290.0925.
2-(Benzo[d][1,3]dioxol-5-yl)-3-nitroimidazo[1,2-a]pyridine
1
3am: yellow solid; mp 198−200 °C; H NMR (400 MHz, CDCl3) δ
9.50−9.48 (d, J = 6.8 Hz, 1 H), 7.81−7.79 (d, J = 8.8 Hz, 1 H), 7.66−
7.62 (m, 1 H), 7.53−7.50 (q, 1 H), 7.429−7.425 (d, 1 H), 7.27−7.24
(m, 1 H), 6.94−6.92 (d, J = 8 Hz, 1 H), 6.05 (s, 2 H); 13C NMR (100
MHz, CDCl3) δ 149.9, 149.4, 147.4, 145.0, 130.9, 128.2, 125.4, 125.0,
118.1, 116.3, 110.4, 108.1, 101.4; IR (neat, cm−1) 3032, 2917, 1628,
1536, 1478, 1213, 1037, 762, 747; HRMS calcd for C14H10N3O4 [M +
H]+ 284.0666, found 284.0673.
Ethyl 3-nitro-2-phenylimidazo[1,2-a]pyridine-7-carboxylate
1
3fa: yellow solid; mp 118−120 °C; H NMR (400 MHz, CDCl3) δ
9.51−9.49 (d, J = 7.2 Hz, 1 H), 8.48 (s, 1 H), 7.92−7.89 (q, 2 H),
7.83−7.81 (q, 1 H), 7.52−7.51 (q, 3 H), 4.51−4.45 (q, J = 7.2 Hz, 2
H), 1.48−1.44 (t, J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ
163.7, 150.8, 144.2, 132.1, 131.4, 130.4, 130.0, 128.2, 127.7, 119.9,
115.4, 62.3, 14.1; IR (neat, cm−1) 3092, 3066, 2922, 2852, 1718, 1530,
1498, 1473, 1362, 1309, 1211, 759, 742, 699; HRMS calcd for
C16H14N3O4 [M + H]+ 312.0979, found 312.0972.
2-(Furan-2-yl)-3-nitroimidazo[1,2-a]pyridine 3an: yellow
1
solid; mp 190−192 °C; H NMR (400 MHz, CDCl3) δ 9.55−9.54
(d, J = 7.2 Hz, 1 H), 7.94−7.93(d, J = 3.6 Hz, 1 H), 7.87−7.85 (d, J =
8.8 Hz, 1 H),7.748−7.746 (d, 1 H), 7.69−7.64 (m, 1 H), 7.28−7.24
(m, 1 H), 6.68−6.66 (m, 1 H); 13C NMR (100 MHz, CDCl3) δ 145.8,
145.69, 145.64, 139.8, 131.4, 128.1, 118.4, 118.1, 116.3, 112.5; IR
(neat, cm−1) 3033, 1633, 1589, 1480, 1351, 1215, 1021, 747; HRMS
calcd for C11H8N3O3 [M + H]+ 230.0560, found 230.0564.
8-Methyl-3-nitro-2-phenylimidazo[1,2-a]pyridine 3ba: yellow
solid; mp 166−168 °C; 1H NMR (400 MHz, CDCl3) δ 9.36−9.34 (d,
J = 6.8 Hz, 1 H), 7.91−7.89 (q, 2 H), 7.51−7.48 (m, 3 H), 7.44−7.42
(d, J = 7.2 Hz, 1 H), 7.17−7.14 (t, 1 H), 2.71 (s, 3 H); 13C NMR (100
MHz, CDCl3) δ 149.6, 145.1, 132.1, 130.0, 129.9, 129.8, 128.5, 128.0,
125.8, 116.3, 16.5; IR (neat, cm−1) 3059, 2923, 1623, 1533, 1474,
1364, 1237, 1154, 749, 695; HRMS calcd for C14H12N3O2 [M + H]+
254.0924, found 254.0916.
ASSOCIATED CONTENT
* Supporting Information
■
S
Spectral data for all new compounds and X-ray data for 3ba
(CIF). This material is available free of charge via the Internet
at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*e-mail: yanrl@lzu.edu.cn; hgs@lzu.edu.cn.
■
8-Methyl-3-nitro-2-m-tolylimidazo[1,2-a]pyridine 3bb: yel-
1
low solid; mp 190−192 °C; H NMR (400 MHz, CDCl3) δ 9.33−
ACKNOWLEDGMENTS
We thank the National Science Foundation (NSF-20732002,
NSF-20090443, and NSF-20872052) for financial support.
■
9.32 (d, J = 6.8 Hz, 1 H), 7.69−7.67 (d, J = 7.2 Hz, 2 H), 7.42−7.35
(m, 2 H), 7.30−7.28 (d, J = 7.6 Hz, 1 H), 7.15−7.12 (t, 1 H), 2.70 (s,
3 H), 2.43 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 149.8, 145.0,
137.7, 132.0, 130.7, 130.4, 129.7, 128.4, 127.9, 127.1, 125.7, 116.3,
21.3, 16.5; IR (neat, cm−1) 3036, 2922, 1621, 1529, 1476, 1363, 1235,
1149, 755, 709; HRMS calcd for C15H14N3O2 [M + H]+ 268.1081,
found 268.1089.
REFERENCES
■
(1) (a) Rupert, K. C.; Henry, J. R.; Dodd, J. H.; Wadsworth, S. A.;
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2-(3-Bromophenyl)-8-methyl-3-nitroimidazo[1,2-a]pyridine
1
3bj: yellow solid; mp 188−190 °C; H NMR (400 MHz, CDCl3) δ
9.35−9.34 (d, J = 6.8 Hz, 1 H), 8.05−8.04 (t, J = 1.6 Hz, 1 H), 7.85−
7.83 (d, J = 8 Hz, 1 H), 7.62−7.60 (q, 1 H), 7.47−7.45 (d, J = 7.2 Hz,
1 H), 7.38−7.34 (t, J = 8 Hz, 1 H), 7.21−7.18 (t, 1 H), 2.72 (s, 3 H);
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129.5, 128.77, 128.74, 125.7, 122.0, 116.7, 16.5; IR (neat, cm−1) 3064,
2924, 1622, 1529, 1473, 1448, 1360, 1233, 1155, 751, 723; HRMS
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8-Methyl-3-nitro-2-p-tolylimidazo[1,2-a]pyridine 3bc: yellow
solid; mp 102−104 °C; 1H NMR (400 MHz, CDCl3) δ 9.34−9.32 (d,
J = 6.8 Hz, 1 H), 7.83−7.81 (d, J = 8 Hz, 2 H), 7.41−7.39 (d, J = 7.2
Hz, 1 H), 7.30−7.28 (d, J = 8.0 Hz, 2 H), 7.14−7.11 (t, J = 7.2 Hz, 1
H), 2.69 (s, 3 H), 2.42 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ
149.8, 145.1, 140.1, 129.9, 129.7, 129.2, 128.7, 128.3, 125.8, 116.2,
21.4, 16.5; IR (neat, cm−1) 3028, 2922, 2854, 1651, 1543, 1476, 1363,
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7.90−7.87 (m, 2 H), 7.74−7.71 (d, J = 8.8 Hz, 1 H), 7.50−7.48 (q, 4
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