Direct catalytic C-H arylation of imidazo[1,2-a]pyridine with aryl bromides using magnetically recyclable Pd-Fe3O4 nanoparticles

Article abstract of DOI:10.1016/j.tet.2013.04.031

The direct C-H arylation of a heteroarene with aryl bromides has been achieved under the catalysis of magnetic nanoparticles. In the presence of bimetallic Pd-Fe₃O₄ heterodimer nanocrystals (1 mol % in palladium), the reaction of imi

Full text of DOI:10.1016/j.tet.2013.04.031

Tetrahedron xxx (2013) 1e5
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Direct catalytic CeH arylation of imidazo[1,2-a]pyridine with aryl
bromides using magnetically recyclable PdeFe3O4 nanoparticles
*
*
Jaewoo Lee, Jooyoung Chung, Sang Moon Byun, B. Moon Kim , Chulbom Lee
Department of Chemistry, Seoul National University, Seoul 151-747, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
The direct CeH arylation of a heteroarene with aryl bromides has been achieved under the catalysis of
magnetic nanoparticles. In the presence of bimetallic PdeFe3O4 heterodimer nanocrystals (1 mol % in
palladium), the reaction of imidazo[1,2-a]pyridine with various aryl bromides gives the corresponding
arylated products with exclusive C3-selectivity. The highly regioselective method is applicable to a wide
range of aryl bromides with varying electronic and steric properties. The PdeFe3O4 nanocrystals can be
recoverable by simple magnetic separation and have been recycled ten times without loss of catalytic
activity.
Received 9 March 2013
Received in revised form 7 April 2013
Accepted 9 April 2013
Available online xxx
Keywords:
Direct arylation
Recyclable magnetic nanoparticles
PdeFe3O4
Ó 2013 Elsevier Ltd. All rights reserved.
Imidazo[1,2-a]pyridine
Aryl bromides
1. Introduction
interest to examine whether the good catalytic activity displayed by
these nanocrystals in Suzuki coupling reactions could be translated
The aryleheteroaryl linkage is an important structural motif in
a wide array of pharmaceuticals, natural products, and functional
materials.1 Among the methods for the formation of heterobiaryl
CeC bonds, transition metal-catalyzed cross-coupling reactions
have been most popular, providing numerous applications.2 How-
ever, traditional cross-couplings, despite their widespread utility,
are unfavorable from the vantage point of atom-economy since they
require preformation of organometallic reagents and inevitably
produce metallic waste of a stoichiometric amount. In this regard,
recent approaches based on transition metal-catalyzed CeH func-
tionalization are attractive, as a specific CeH bond of heteroarenes
may be directly activated to undergo regioselective arylation.3 Great
advances have indeed been made in the last decade for the direct
CeH arylation of heteroarenes using various transition metal cata-
lysts, such as Pd, Rh, Cu, Ni, Ir, Ru, and Fe.4 Notably, phosphine-free
conditions, which presumably involve nanoparticle formations have
also made their way to heterobiaryl synthesis with potential ad-
vantages from both homogeneous and heterogeneous catalysis.5
In conjunction with our studies on the utility of magnetically
separable Fe3O4 nanoparticles,6 we questioned about the ability of
the bimetallic PdeFe3O4 nanocrystals with a unique hetero-dimeric
morphology to mediate catalytic reactions.7 It was of particular
into other types of transformations. Recently, a variety of magnetic
nanoparticles amenable for easy separation and recovery have been
synthesized and applied as catalysts to a range of chemical reactions.8
However, their utility in direct CeH functionalization processes re-
mains largely to be established.9 Given the importance of hetero-
biaryl synthesis and the practical benefits associated with using
magnetic nanoparticles, it would be of great significance to develop
a protocol for the direct CeH arylation of heteroarenes that takes
advantage of magnetically recoverable nanocatalysts. Described here
are the results of our studies on the CeH arylation of imidazo[1,2-a]
pyridine with aryl bromides through a catalysis mediated by mag-
netically separable and hence reusable PdeFe3O4 nanocrystals.
2. Results and discussion
The PdeFe3O4 heterodimer nanocrystals were prepared from
a solution of Pd(acac)2, Fe(acac)2, oleylamine, and oleic acid using
a two-step thermal decomposition procedure according to the
previous report.7 The synthesis could be easily practiced up to a 2 g
scale (2.45 wt % Pd), and the obtained nanocrystals were bench
stable and could be stored at ambient temperature for several weeks
without alteration in shape or reactivity. As shown in the trans-
mission electron microscopy (TEM) images (Fig. 1a and b), nearly all
of the nanoparticles were a 1:1 hybrid bimetallic system composed
of a single Pd nanosphere (w6 nm in diameter) and a faceted Fe3O4
nanocrystal (w30 nm in dimension). All of the peaks in the X-ray
* Corresponding authors. Tel.: þ82 2 880 6650; fax: þ82 2 875 6636; e-mail
addresses: kimbm@snu.ac.kr (B.M. Kim), chulbom@snu.ac.kr (C. Lee).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.031
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2
J. Lee et al. / Tetrahedron xxx (2013) 1e5
under reflux (166 ꢀC) in the presence of PdeFe3O4 nanocrystals
(1 mol % in Pd) and NaOAc (2 equiv), the reaction was completed in
12 h to give rise to the C3-arylated product 3a exclusively in 88%
yield (Table 1, entry 1). Similarly, the reactions employing KOAc or
CsOAc as a base also gave 3a, but in lower yields (Table 1, entries 2
and 3). In contrast, the use of AgOAc resulted in a low conversion,
and 3a was obtained only in a yield of 5% from a sluggish reaction
(Table 1, entry 4). Various carbonate bases were also examined,
among, which K2CO3 proved to be most effective (Table 1, entries
ꢀ
5e7). It was notable that Na2CO3 performed poorly vis-a-vis NaOAc,
whereas K2CO3 and KOAc gave comparable results (Table 1, entries
1 and 2 vs 5 and 6). In a brief survey of solvents, N-methyl-2-
pyrrolidone (NMP) was found to be equally effective as DMA
while the reaction in N,N-dimethylformamide (DMF) led to a sig-
nificant decrease in both the reaction rate and yield. It should be
noted that in contrast to the report on arene CeH arylation,9 the
PdeFe3O4 nanocrystals were absolutely necessary for this hetero-
arene CeH arylation reaction as verified by a control experiments
where no reaction occurred in the absence of PdeFe3O4 or in the
presence of only Fe3O4 even at a higher reaction temperature for
a prolonged reaction time. The arylation was also performed with
chloro and iodo substrates for comparison with 2a. Whereas 4-
chloronitrobenzene did not undergo the arylation but instead
decomposed slowly under the conditions of entry 1, the reaction of
4-iodonitrobenzene was completed in 9 h to produce 3a in 87%
yield, indicating the differential reactivity of aryl halides in this
process.
Fig. 1. (a) TEM image, (b) HRTEM image, (c) XRD pattern, and (d) VSM MeH curve of
PdeFe3O4 measured at 300 K.
Having established the viability of PdeFe3O4 nanocrystals as the
catalyst to effect the direct CeH arylation of imidazo[1,2-a]pyridine,
we set out to examine the scope of the reaction. It was found that
the conditions were general and efficient with a wide range of aryl
bromides (Table 2). Under the optimal conditions derived from
screening experiments (1.0 mol % Pd catalyst, NaOAc, DMA, 166 ꢀC,
12 h), aryl bromides having differential electronic and steric
properties participated well in the cross-coupling reaction with
imidazo[1,2-a]pyridine (1) to afford the corresponding C3-arylated
products 3. In no case, was detected the formation of other
regioisomers including the C2-arylated product. While electron-
poor (Table 2, entries 1e4) as well as electron-rich (Table 2, entry
6) aryl bromides underwent the direct CeH arylation, the reaction
of the latter was less efficient to give a low yield.13 A variety of
functional groups, such as nitrile (3b and 3h), aldehyde (3c and 3i),
ketone (3d), chloride (3e), and ether (3g), were tolerated. When the
reaction was performed with 4-bromochlorobenzene (2e), the de-
sired arylated product 3e was produced in 67% yield with the
chloride group unaffected, suggesting the possibility of carrying out
an additional cross-coupling process. The CeH arylation reaction
was insensitive to the substituent present in aryl bromides as
shown by the comparable outcomes from the reactions of para- and
meta-substituted aryl bromides (Table 2, entries 1 and 2 vs 7 and 8).
Furthermore, polycyclic aryl bromides including ortho-fused sub-
strates 2k and 2l could also be successfully employed for the re-
action (Table 2, entries 9e11). In these reactions, both 1- and 2-
bromonaphthalenes 2j and 2k proved to be equally competent
participants of the cross-coupling reaction with 1 to furnish 3j and
3k, respectively. It was worthy of note that 9-bromoanthracene (2l),
a substrate with high steric congestion, was also found to be suit-
able for the reaction, furnishing the anthracenylated product 3l in
58% yield (Table 2, entry 11).
diffraction (XRD) pattern could also be assigned to the corre-
sponding lattice planes of face-centered-cubic (fcc) Pd and Fe3O4
crystals in accordance with the bimetallic heterodimer structure
(Fig. 1c). The MeH curve analysis using a vibrating sample magne-
tometer (VSM) showed the hybrid nanocrystals to be soft ferri-
magnetic with a low coercivity, indicating the suitability for their
use in magnetic separation and recovery applications (Fig. 1d).10
The probe of PdeFe3O4 nanocrystals for their catalytic activity to
mediate a direct CeH arylation was conducted using imidazo[1,2-a]
pyridine (1),11 a key structural component of important pharma-
ceuticals as exemplified by Zolpidem and Miroprofen. Our explo-
ration began with screening various parameters of the cross-
coupling reaction between
1 and 4-bromonitrobenzene (2a)
employing phosphine-free conditions (Table 1).12 When a 1.5:1
mixture of 1 and 2a in N,N-dimethylacetamide (DMA) was heated
Table 1
Direct arylation of imidazo[1,2-a]pyridine with 4-bromonitrobenzenea
Entry
Solvent
Base
Temp (ꢀC)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMF
NMP
NMP
NaOAc
KOAc
166
166
166
166
166
166
166
120
166
180
12
12
12
18
30
12
12
21
12
10
88
75
62
5
30
82
58
12
87
88
CsOAc
AgOAc
Na2CO3
K2CO3
Cs2CO3
NaOAc
NaOAc
NaOAc
In order to investigate the recoverability and reusability of the
PdeFe3O4 nanocrystals, we carried out a set of catalyst recycling
experiments (Table 3). Under the standard conditions, the cross-
coupling reaction of 1 with 4-bromonitrobenzene (2a) was re-
peated using the nanocrystals that were recovered each time from
the previous run. Remarkably, the catalytic activity was found to
remain unaltered throughout 10 runs to produce 3a at the same
10
a
All reactions were carried out with 4-bromonitrobenzene (0.50 mmol), imidazo
[1,2-a]pyridine (0.75 mmol), base (1.0 mmol), and PdeFe3O4 (0.005 mmol, 1 mol %
in Pd) at 0.25 M concentrations.
b
Isolated yields based on 2a.
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J. Lee et al. / Tetrahedron xxx (2013) 1e5
3
Table 2
[1,2-a]pyridine with a wide variety of aryl bromides to give rise to
mono-arylated products in high yield. The reaction is highly regio-
selective to form only 3-arylated products exclusively. Also note-
worthy is that the reaction is carried out under phosphine-free
conditions. The PdeFe3O4 heterodimeric nanocrystals can be easily
recovered by using an external permanent magnet, and the catalytic
activity remains unaltered even after recycling 10 times. The effi-
ciency, operational simplicity, cost effectiveness, and environmen-
tally benign features of the present PdeFe3O4 catalyst system lends
itself to large-scale applications including industrial processes.
Current efforts are aimed at exploring the full potential of the
nanoparticle catalyst.
Scope of the direct arylation of imidazo[1,2-a]pyridine with aryl bromidesa
Entry
1
Aryl bromide
Br
Product
Yield (%)b
95
2b
2c
3b
CN
O
2
3c
82
Br
H
4. Experimental
O
2d
2e
3
4
3d
3e
94
67
4.1. General remarks
Br
Me
All the reactions were performed using oven-dried glassware
and commercial reagents were used without further purification
unless otherwise noted. Solvents were used by passing through
activated alumina columns of a solvent purification systems from
Glass Contour. Sonication was carried out in a 120 W ultrasonic
bath (Branson, B-3210). The progress of reactions was checked on
thin layer chromatography (TLC) plates and the spots were visu-
alized under UV light and/or by charring the TLC plate after dipping
it into a KMnO4 solution. Flash column chromatography was per-
formed on silica gel eluting with a mixture of hexaneseethyl ace-
tate. 1H and 13C NMR spectra were obtained on Agilent MR DD2
(400 MHz) spectrophotometer.
Br
Br
Br
Cl
2f
5
6
7
3f
81
42
94
Me
2g
2h
3g
3h
OMe
Br
Br
CN
O
2i
8
3i
74
4.2. Preparation of the catalyst
H
The synthesis of PdeFe3O4 was performed by two-step thermal
decomposition of a mixture composed of iron acetate, palladium
acetate, oleylamine, and oleic acid. In a typical experiment, 200 mg of
Pd(acac)2 (0.66 mmol) and 14 g of Fe(acac)3 (40 mmol) were added
into a solution containing 120 mL of oleylamine (350 mmol) and
80 mL of oleic acid (250 mmol), and the mixture was heated to 120 ꢀC
in reduced pressure with vigorous stirring for 2 h. The resulting dark
brown solution was heated to 220 ꢀC under Ar atmosphere at
a heating rate of 2 ꢀC/min and keptatthistemperature for 30min, and
then it was further heated to 300 ꢀC at the same heating rate and aged
for 30min. Aftercooled to ambient temperature, the reaction mixture
was treated with 250 mL of ethanol to induce precipitation, and the
resultant powdery nanocrystals were retrieved by centrifugation
(1700 rpm, 15 min). The nanocrystals were purified by dispersing in
150mL of hexanes and collectingwith a neodymiummagnet (3880 G,
50 mm diameterꢁ10 mm thick). These washing cycles were repeated
until the hexane layer showed no color, at which point the PdeFe3O4
nanocrystals were dried under vacuum (2.8 g).
2j
2k
9
3j
75
70
Br
10
3k
Br
Br
2l
11
3l
58
a
All reactions were carried out with imidazo[1,2-a]pyridine (0.75 mmol), aryl
bromide (0.50 mmol), NaOAc (1.0 mmol), and PdeFe3O4 (0.005 mmol, 1 mol % in Pd)
in DMA (0.25 M) at 166 ꢀC for 12 h.
b
Isolated yields based on aryl bromide 2.
Table 3
Recycling of the PdeFe3O4 nanocrystals for the reaction of 1 with 2a
Run
Yield
1
88
2
87
3
83
4
85
5
85
6
84
7
85
8
84
9
87
10
86
4.3. Characterization of the catalyst
All transmission electron microscopy (TEM) and high resolution
(HRTEM) images were obtained on a JEOL EM-2010 microscope at
an accelerating voltage of 200 kV. The powder X-ray diffraction
(XRD) was performed using a Rigaku D/Max-3C diffractometer (Cu
level of high efficiency (average yield 85%). In these recycling ex-
periments, more than 98% of the nanocrystals could be recovered
through a simple procedure involving separation by an outer
magnet and catalyst purification by dispersionecollection cycles.
Ka
radiation,
l¼0.15418 nm). The magnetic properties (MeH curve)
were characterized using
a
vibrating sample magnetometer
(Quantum Design PPMS VSM) at 300 K.
3. Conclusion
4.4. Recycle of the catalyst
In summary, we have described the direct CeH arylation of
a heteroarene via magnetically recoverable palladium nanoparticle-
mediated catalysis. The Pd nanosphere immobilized on faceted
Fe3O4 nanocrystals efficiently catalyzes the arylation of imidazo
After completion of the reaction, PdeFe3O4 nanocrystals were
placed on the bottom of the flask by a neodymium magnet, and the
supernatant solution was removed. The separated nanocrystal
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4
J. Lee et al. / Tetrahedron xxx (2013) 1e5
catalyst was washed successively with 10 mL of water, ethanol,
ethyl acetate, dichloromethane, and hexanes, and then dried. In
a typical recycling experiment, more than 98% of PdeFe3O4 could
be recovered.
3H); 13C NMR (100 MHz, CDCl3)
d 159.8,146.0,132.2,129.8,125.7,124.1,
123.5, 121.8, 118.4, 114.9, 112.5, 55.6.
4.6.8. 3-Imidazo[1,2-a]pyridine-3-ylbenzonitrile (3h).11f Yield (94%)
from 1 and 3-bromobenzonitrile (2h). 1H NMR (400 MHz, CDCl3)
4.5. General procedure for the Pd-catalyzed CeH arylation
d
8.27 (dd, J¼6.9, 1.1 Hz, 1H), 7.83 (s, 1H), 7.80e7.75 (m, 1H), 7.72 (s,
1H), 7.70e7.57 (m, 3H), 7.25e7.18 (m, 1H), 6.90e6.83 (m, 1H); 13C
NMR (100 MHz, CDCl3) 146.8, 133.7, 132.0, 131.5, 131.0, 130.9,
In DMA (2 mL) degassed by a stream of argon gas for 10 min
were dissolved aryl bromide 2 (0.5 mmol), imidazo[1,2-a]pyridine
(1, 0.0886 g, 0.75 mmol), NaOAc (0.0821 g, 1 mmol), and PdeFe3O4
(0.0217 g, 0.005 mmol). The resulting suspension was degassed by
argon for 10 min, sonicated for 3 min, and stirred at 166 ꢀC for 12 h.
After cooled to room temperature, the reaction mixture was filtered
with a short silica gel pad and concentrated under reduced pres-
sure. Alternatively, the reaction mixture was concentrated after
magnetic separation of PdeFe3O4. The crude product was purified
by flash column chromatography on a silica gel column.
d
130.4, 125.1, 123.5, 123.0, 118.7, 118.4, 113.7, 113.4.
4.6.9. 3-Imidazo[1,2-a]pyridin-3-ylbenzaldehyde (3i).11f Yield (74%)
from 1 and 3-bromobenzaldehyde (2i). 1H NMR (400 MHz, CDCl3)
d
10.05 (s, 1H), 8.30 (dd, J¼6.9, 1.0 Hz,1H), 8.04 (t, J¼1.4 Hz,1H), 7.87
(dt, J¼7.6, 1.3 Hz, 1H), 7.82e7.75 (m, 1H), 7.72 (s, 1H), 7.68e7.60 (m,
2H), 7.24e7.14 (m, 1H), 6.82 (td, J¼6.9, 1.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3)
d 191.8, 146.6, 137.3, 133.7, 133.3, 130.5, 130.2,
129.6, 128.3, 124.9, 124.4, 123.2, 118.5, 113.2.
4.6. Characterization of the arylation products
4.6.10. 3-Naphthalene-2-yl-imidazo[1,2-a]pyridine (3j).11f Yield (75%)
from 1 and 2-bromonaphthalene (2j). 1H NMR (400 MHz, CDCl3)
4.6.1. 3-(4-Nitrophenyl)-imidazo[1,2-a]pyridine (3a).14 Yield (88%)
from 1 and 4-bromonitrobenzene (2a). 1H NMR (400 MHz, CDCl3)
d
8.44 (d, J¼7.0 Hz, 1H), 8.03 (s, 1H), 7.98 (d, J¼8.5 Hz, 1H), 7.93e7.87
(m, 2H), 7.81 (s, 1H), 7.71 (d, J¼9.1 Hz, 1H), 7.67 (dd, J¼8.5,1.7 Hz, 1H),
7.59e7.51 (m, 2H), 7.23 (ddd, J¼9.1, 6.7, 1.2 Hz, 1H), 6.84 (td, J¼6.8,
d
8.42 (d, J¼7.0 Hz, 1H), 8.38 (d, J¼8.7 Hz, 2H), 7.86 (s, 1H), 7.81e7.69
(m, 3H), 7.30 (ddd, J¼8.6, 6.8, 0.7 Hz, 1H), 6.94 (t, J¼6.6 Hz, 1H); 13
C
1.1 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 146.5, 133.8, 133.2, 133.0,
NMR (100 MHz, CDCl3)
d
147.5, 147.0,136.1,134.9,127.7, 125.6,125.0,
129.2, 128.2, 128.1, 127.0, 126.89, 126.87, 126.7, 126.0, 124.5, 123.6,
118.6, 112.9.
123.9, 123.4, 119.0, 113.8.
4.6.2. 4-Imidazo[1,2-a]pyridine-3-ylbenzonitrile (3b).11f Yield (95%)
from 1 and 4-bromobenzonitrile (2b). 1H NMR (400 MHz, CDCl3)
4.6.11. 3-Naphthalene-1-yl-imidazo[1,2-a]pyridine (3k).15 Yield (70%)
from 1 and 1-bromonaphthalene (2k). 1H NMR (400 MHz, CDCl3)
d
8.37 (dt, J¼7.0, 1.1 Hz,1H), 7.86e7.76 (m, 3H), 7.71 (qt, J¼2.1, 1.4 Hz,
d
7.98 (dt, J¼16.0, 6.3 Hz, 2H), 7.80 (s, 1H), 7.74 (d, J¼9.1 Hz, 1H), 7.71
3H), 7.32e7.23 (m, 1H), 6.90 (td, J¼6.9, 1.2 Hz, 1H); 13C NMR
(d, J¼6.9 Hz, 1H), 7.62e7.56 (m, 2H), 7.55e7.47 (m, 2H), 7.46e7.38 (m,
(100 MHz, CDCl3)
123.3, 118.9, 118.8, 113.6, 111.4.
d 147.3, 134.4, 134.2, 133.3, 127.9, 125.4, 124.2,
1H), 7.21 (tt, J¼17.6, 6.1 Hz, 1H), 6.69 (t, J¼6.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 146.0, 134.1, 134.0, 132.2, 129.8, 129.3, 128.9, 127.1,
126.6, 126.4, 125.8, 125.4, 124.5, 124.3, 118.2, 112.5.
4.6.3. 4-Imidazo[1,2-a]pyridin-3-ylbenzaldehyde (3c).11f Yield (82%)
from 1 and 4-bromobenzaldehyde (2c). 1H NMR (400 MHz, CDCl3)
4.6.12. 3-Anthracen-9-ylimidazo[1,2-a]pyridine (3l).11f Yield (58%)
from 1 and 9-bromoanthracene (2l). 1H NMR (400 MHz, CDCl3)
d
10.07 (s, 1H), 8.44 (d, J¼6.9 Hz, 1H), 8.04 (t, J¼9.9 Hz, 2H), 7.84 (s,
1H), 7.77 (d, J¼8.1 Hz, 2H), 7.72 (d, J¼9.1 Hz, 1H), 7.34e7.21 (m, 1H),
d
8.49 (s, 1H), 7.96 (d, J¼8.4 Hz, 2H), 7.80 (s, 1H), 7.71 (d, J¼9.1 Hz,
6.91 (t, J¼6.7 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
191.5, 147.2,
1H), 7.42 (d, J¼8.7 Hz, 2H), 7.39e7.32 (m, 2H), 7.27e7.20 (m, 2H),
135.5, 134.4, 130.8, 127.7, 125.2, 124.7, 123.5, 118.8, 113.4.
7.17 (t, J¼6.9 Hz, 1H), 7.14e7.06 (m, 1H), 6.47 (t, J¼6.7 Hz, 1H); 13C
NMR (100 MHz, CDCl3)
d 146.1, 135.6, 133.6, 131.9, 131.6, 129.3,
4.6.4. 4-Imidazo[1,2-a]pyridin-3-ylacetophenone (3d).11f Yield (94%)
from 1 and 4-bromoacetophenone (2d). 1H NMR (400 MHz, CDCl3)
128.9, 126.9, 125.7, 124.5, 124.2, 122.1, 120.8, 118.1, 112.4.
d
8.42 (d, J¼7.0 Hz, 1H), 8.11 (d, J¼8.3 Hz, 2H), 7.81 (s, 1H), 7.74e7.65
Acknowledgements
(m, 3H), 7.29e7.22 (m, 1H), 6.89 (t, J¼6.8 Hz, 1H), 2.67 (s, 3H); 13C
NMR (100 MHz, CDCl3)
127.5, 125.0, 124.9, 123.5, 118.7, 113.3, 26.8.
d 197.4, 147.0, 136.3, 134.2, 134.0, 129.5,
Support for this work was provided through the BRL (Basic
Research Laboratory) program of the NRF (National Research
Foundation) of Korea.
4.6.5. 3-(4-Chlorophenyl)-imidazo[1,2-a]pyridine (3e).11e Yield (67%)
from 1 and 1-bromo-4-chlorobenzene (2e). 1H NMR (400 MHz,
Supplementary data
CDCl3)
d
8.27 (d, J¼7.0 Hz, 1H), 7.67 (d, J¼10.6 Hz, 2H), 7.49 (s, 4H),
7.21 (ddd, J¼9.0, 6.7, 1.1 Hz,1H), 6.82 (td, J¼6.9, 0.8 Hz, 1H); 13C NMR
1H and 13C NMR spectra for all compounds. Supplementary data
related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2013.04.031.
(100 MHz, CDCl3)
d 146.4, 134.2, 134.2, 133.0, 129.7, 129.4, 128.0,
124.6, 123.3, 118.6, 113.0.
4.6.6. 3-(4-Methylphenyl)-imidazo[1,2-a]pyridine (3f).15 Yield (81%)
References and notes
from 1 and 4-bromotoluene (2f). 1H NMR (400 MHz, CDCl3)
d 8.31
(d, J¼7.0 Hz, 1H), 7.66 (d, J¼8.2 Hz, 2H), 7.45 (d, J¼7.1 Hz, 2H), 7.32
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Please cite this article in press as: Lee, J.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.04.031