Straightforward synthesis of various 2,3-diarylimidazo[1,2-a]pyridines in peg400 medium through one-pot condensation and C-H arylation

Article abstract of DOI:10.1002/ejoc.201402079

PEG₄₀₀ is described herein as a suitable medium for the condensation of various 2-amino pyridines with α-bromo ketones. 2-Arylimidazo[1,2-a]pyridines were synthetized in a short time through microwave irradiation in moderate to excellent yields

Full text of DOI:10.1002/ejoc.201402079

Job/Unit: O42079
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Date: 12-06-14 17:05:48
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FULL PAPER
DOI: 10.1002/ejoc.201402079
Straightforward Synthesis of Various 2,3-Diarylimidazo[1,2-a]pyridines in
PEG400 Medium through One-Pot Condensation and C–H Arylation
Marie-Aude Hiebel,[a] Yacoub Fall,[a] Marie-Christine Scherrmann,[b] and
Sabine Berteina-Raboin*[a]
Keywords: Synthetic methods / Nitrogen heterocycles / C–H activation
PEG400 is described herein as a suitable medium for the con-
densation of various 2-amino pyridines with α-bromo
ketones. 2-Arylimidazo[1,2-a]pyridines were synthetized in
a short time through microwave irradiation in moderate to
excellent yields. After optimization, a convenient one-pot
process enabled access to 2,3-diarylimidazo[1,2-a]pyridines
by using a reduced amount of palladium catalyst without li-
gand for the C–H arylation step in the same environmentally-
sound medium.
azo[1,2-a]pyridines are generally synthesized through a con-
densation between 2-aminopyridines and α-haloketones in
polar organic solvents.[1–7] To introduce further diversity
our group, among others, reported metal-catalyzed cross-
coupling reactions. However, these methods such as
Suzuki-,[8] Stille-,[9] Heck-,[10] Sonogashira-,[11] or Negishi-
type[12] reactions require a halogenated precursor, which
makes the sequence longer and increases waste production.
Recently, direct C–H bond functionalization became an ele-
gant and requisite method to introduce various substitu-
tions in an environmentally improved route.[6,13] In our ef-
fort to develop environmentally benign tools, we have con-
tinuously tried to promote the use of non-toxic media.[14]
Recently, some polymer media have been used as new sol-
vents in organic synthesis, in particular polyethylene glycol
(PEG).[15] By convention, PEG usually represents polymers
with a molecular weight that does not exceed 20000 and
the notation PEG400 means poly(ethylene glycol) with an
average molecular weight of 400. PEG400 is a viscous sus-
tainable liquid soluble in water and many organic solvents.
This medium has the advantage of being non-toxic, odor-
less, neutral, non-volatile, and non-irritating and is used in
a variety of pharmaceuticals and medications. Herein we
report the use of PEG400 as an efficient medium to synthe-
size and functionalize the imidazo[1,2-a]pyridine moiety in
a one-pot condensation and C–H-activation process.
Introduction
Imidazo[1,2-a]pyridines exhibit a broad range of bio-
logical activities.[1] Some synthetic drugs that contain this
pyridine core have been commercialized such as the sedative
Zolpidem, the anxiolytic Alpidem or Saridipem, and the
heart-failure drug Olprione (Figure 1).
Figure 1. Examples of imidazoheterocyclic-containing therapeutics.
More specifically, the 2,3-diarylimidazo[1,2-a]pyridine
family has shown antiprotozoal,[2] antiherpes,[3] and anti-
apoptotic activities,[4] and also acts as a kinase inhibitor[5]
and antileishmanial agent.[6] Its value in the pharmaceutical
and agrochemical area has therefore prompted continued
effort to obtain efficiently this key structural unit.[1–6] Imid-
Results and Discussion
[a] Institut de Chimie Organique et Analytique (ICOA), Université
d’Orléans, UMR-CNRS 7311,
BP 6759, rue de Chartres, 45067 Orléans cedex 2, France
E-mail: sabine.berteina-raboin@univ-orleans.fr
www.icoa.fr
We first focused on the condensation of 2-aminopryrid-
ine (1 equiv.) and 2-bromoacetophenone (1 equiv.) and de-
cided to optimize the conditions by using benign solvents.
In the presence of sodium hydrogen carbonate (2 equiv.) at
room temperature in PEG400, 2-phenylimidazo[1,2-a]pyr-
idine (1a) was obtained in moderate yield after 22 h
[b] Institut de Chimie Moléculaire et des Matériaux d’Orsay, UMR
CNRS 8182, Université Paris-Sud,
Bâtiment 410, 91400 Orsay, France
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402079.
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M.-A. Hiebel, Y. Fall, M.-C. Scherrmann, S. Berteina-Raboin
FULL PAPER
(Table 1, Entry 1). A decrease in the yield was noticed in Table 1. Optimization of the condensation step in PEG400 media.
water, perhaps owing to the poor solubility of the reagents
in this medium. To shorten the reaction time, microwave
irradiation was used, and completion of the reaction was
obtained after 10 min. With its permanent dipole and its
high boiling point, PEG is an excellent solvent for micro-
wave irradiation.[16] However, some degradation was ob-
Entry Base [equiv.]
V [mL] T [°C][a] t [min] Yield[b] [%]
served when the temperature rose above 120 °C (Table 1,
Entries 2–4). Then, the amount of base was studied, and
even if 1a was obtained in 78% with 3 equiv. of NaHCO3,
the improvement was not sufficient to justify the use of ex-
cess base (Table 1, Entries 3 and 5–6).
Dilution of the mixture appeared to have no influence
on the reaction, nor did the use of potassium carbonate,
whereas cesium carbonate induced a drastic drop in yield
(Table 1, Entries 9 and 10). Finally, the optimal reaction
conditions chosen were irradiation of a stoichiometric
amount of 2-aminopyridine and 2-bromoacetophenone,
and NaHCO3 at 120 °C for 10 min in PEG400 (8 mL/mmol).
1
2
3
4
5
6
7
8
9
10
NaHCO3 (2)
NaHCO3 (2)
NaHCO3 (2)
NaHCO3 (2)
NaHCO3 (1)
NaHCO3 (3)
NaHCO3 (1)
NaHCO3 (1)
Cs2CO3 (1)
8
8
8
8
8
8
16
4
8
8
r.t.
22[c]
10
10
10
10
10
10
10
10
10
61 (49)[d]
100
120
160
120
120
120
120
120
120
73
73 (72)[e]
61
73 (55)[f]
78
68
70
38
68
K2CO3 (1)
[a] Microwave irradiation. [b] Isolated yields. [c] Hours. [d] Reac-
tion in water. [e] 20 min of irradiation. [f] Reaction performed at
100 °C.
Table 2. Condensation of various 2-aminopyridine with α-bromo ketones in PEG400 media.
2
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Synthesis of Various 2,3-Diarylimidazo[1,2-a]pyridines
With optimized conditions in hand, the scope and limita- substrates with substitutions in ortho and meta positions
tion of the reaction were examined (Table 2). Initially, con- indicated that steric hindrance had an influence on the C–
densation with different α-bromo ketones with 2-amino- H-arylation step (2b and 2c). An unusual solubility issue
pyridine was attempted. Electron-withdrawing or donating with intermediate 1g in PEG400 could explain the moderate
groups on various positions on the aromatic ring exhibited yield of 2g. In addition, various aryl bromides were used.
no influence and the expected product was obtained in ex- Unfortunately, failure in the introduction of 2-bromotolu-
cellent yield (1a–1g).
ene confirmed that bulky substituents disturbed the reac-
Different 2-aminopyridines were then used for the reac- tion even if the reaction time was increased (2h).
tion. 2-Phenylimidazo[1,2-a]pyridines substituted in posi-
tion 6, 7 and 8 were isolated in good yield with electron-
donating substituents (1h–1j and 1l). However, mild or
moderate electron-attracting groups in 6 and 7, such as
halogen, trifluoromethyl or ester groups reduced the
nucleophilic activity of the primary amine or of the endo-
cyclic nitrogen, moderating the yield of the reaction (1k and
1m–1p). Finally, this reaction tolerated alkyl, ether, ester,
nitroso, trifluoromethyl, and halogen-containing moieties.
We studied C–H activation at C3 position (Table 3). The
experimental conditions described by Doucet[13g] were at-
tempted, but only traces of the desired product were ob-
tained. Fortunately, a higher amount of Pd(OAc)2 (1 mol-
%) enabled formation of 2a in excellent yield without extra
addition of ligand (Table 3, Entry 2), and the reaction was
almost quantitative when 2.5 mol-% of catalyst was used.
However we decided to promote a lower catalyst loading.
We then examined the influence of the nature of the base
on conversion. Surprisingly, conversion of the reaction was
incomplete with CsOAc and NaOAc, (26 and 64%, respec-
tively). On the other hand, carbonated bases gave poorer
results (Table 3, Entries 6–8) and despite the possible crown
effect of PEG400, only starting material was recovered with
potassium carbonate and potassium hydroxide.[17] Micro-
wave irradiation significantly reduced the reaction time
from 24 to 1 h. The resulting optimal reaction conditions
were irradiation of 1a with bromobenzene (1.5 equiv.),
KOAc (2 equiv.), and Pd(OAc)2 (1 mol-%) in PEG400
(8 mL/mmol) at 180 °C for 1 h. With these optimized condi-
tions for C–H arylation, we decided to apply them in the
sequential one-pot condensation and C–H arylation pro-
cedure (Table 3, Entries 12–16). Disappointingly, in this
case the conversion was incomplete because 34% of 1a was
isolated after the second microwave irradiation. A longer
reaction time and an increase in the amount of catalyst re-
sulted in no significant change. However a larger amount
of base combined with a higher temperature led to comple-
tion of the reaction (Table 3, Entry 16) and 2a was isolated
in 69% yield, which was consistent with the result of the
two-step procedure (66%). In an endeavor to expand the
scope of the methodology, the one-pot procedure was ap-
plied to different α-bromo ketones, aryl bromides, and 2-
aminopyridines (Table 4). To our delight, the expected
Table 3. C–H arylation and one-pot optimization in PEG400 media.
[a]
Entry Pd(OAc)2
Base
t [h]
T [°C]
Yield[b]
1
2
3
4
5
6
7
8
9
10
0.1
1
2.5
1
1
1
1
1
1
1
KOAc
KOAc
KOAc
CsOAc
NaOAc
NaHCO3
Cs2CO3
K2CO3
KOH
16
24
24
24
24
24
24
24
24
2
150
150
150
150
150
150
150
150
150
180
(MW)
180
(MW)
180
(MW)
180
(MW)
180
(MW)
180
(MW)
220
traces[c]
93
96
26[d]
64[d]
17[d]
[e]
–
[f]
–
[f]
–
KOAc
93
90
11
12
13
14
15
16
1
1
1
2
1
1
KOAc
1
1
2
1
1
1
KOAc
48[g]
KOAc
75[d]
KOAc
72[d]
KOAc[h]
KOAc[h]
49[d]
100[d] (69)[g]
(MW)
[a] In mol-%. [b] Isolated yields. [c] 1 equiv. of PhBr and 1.5 equiv.
1
of 1a were used. [d] Yield as calculated by H NMR spectroscopy.
[e] 1a recovered. [f] Degradation. [g] Isolated yield from the sequen-
tial one-pot procedure; 34% of 1a was recovered. [h] Introduction
of 4 equiv. of KOAc.
However functional groups including electron-rich and
products were exclusively afforded in moderate to excellent electron-withdrawing groups in the para and meta positions
yields. Significant steric and/or electronic effects of the sub- were well tolerated. 4-Bromoanisole and 4-bromotoluene
stituents on the reactivity were observed. The result re- required only a longer reaction time for the C–H-arylation
vealed that varying the aryl group at C2 induced moderate step. Modification of the imidazo core was then attempted.
changes in reactivity on C3. Electron-rich and electron- Mild electron-donating and -withdrawing groups gave the
withdrawing groups in the para position were well tolerated expected products in moderate to good yields over the two-
(2d–2f). However, partial conversion or a lower yield for step process (2s–2w), but no coupling product was observed
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M.-A. Hiebel, Y. Fall, M.-C. Scherrmann, S. Berteina-Raboin
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Table 4. Synthesis of various 2,3-diarylimidazo[1,2-a]pyridines in a cept for the synthesis of 2u in which significant degradation
sequential one-pot process in PEG400 medium.
was observed, no cleavage of the C–Cl bond was noticed,
allowing further transformations (2e and 2x). A series of
functional groups such as alkyl, ether, halogen, nitro, tri-
fluoromethyl, and aldehyde were compatible under these ex-
perimental conditions. But unlike previously, ester groups
were not tolerated (2q and 2y).
Conclusions
We have developed an efficient method to obtain various
2,3-diarylimidazo[1,2-a]pyridines in PEG400. The salient
features of our method are the facile introduction of miscel-
laneous aryl substituents in a one-pot manner from com-
mercially available starting materials in an environmentally-
friendly alternative solvent. The first step is the formation
of the 2-arylimidazo[1,2-a]pyridine core by condensation
between different 2-aminopyridines and α-bromo ketones,
followed directly by C–H activation at C3. Various 2,3-di-
arylimidazo[1,2-a]pyridines have been synthetized in mod-
erate to excellent yields that demonstrates the generality of
this method.
Experimental Section
General: All reagents were purchased from commercial suppliers
and were used without further purification. Microwave assisted re-
actions were carried out in a Biotage Initiator microwave synthesis
instrument and temperatures were measured with an IR sensor.
The reactions were monitored by thin-layer chromatography (TLC)
analysis with silica gel (60 F254) plates. Compounds were visual-
ized by UV irradiation. Flash column chromatography was per-
formed with silica gel 60 (230–400 mesh, 0.040–0.063 mm). Melting
1
points were recorded with samples in open capillary tubes. H and
13C NMR spectra were recorded with a Bruker spectrometer at
250 MHz (13C, 62.9 MHz). Chemical shift signals are reported rela-
tive to tetramethylsilane as internal standard. HRMS were per-
formed on a Maxis Bruker 4G by the “Federation de Recherche”
ICOA/CBM (FR2708) platform.
General Procedure for the Synthesis of 1a–1o: 2-Aminopyridine
(1 mmol), α-bromo ketone (1 mmol) and NaHCO3 (1 mmol) were
dissolved in PEG400 (8 mL) in a sealed vial before being irradiated
for 10 min at 120 °C. Then AcOEt (10 mL) and a saturated solu-
tion of NaHCO3 (10 mL) were added to the reaction mixture. The
resulting aqueous layer was extracted with AcOEt (3ϫ 5 mL). The
combined organic phase was then washed with a saturated solution
of NaHCO3 (5ϫ 5 mL) and dried with MgSO4. After filtration
and concentration under reduced pressure the crude product was
purified either by recrystallization when specified or by flash
chromatography with a mixture of ethyl acetate and petroleum
ether (10–40%) as eluent to provide the expected product.
2-Phenylimidazo[1,2-a]pyridine (1a):[18] White solid, m.p. 131.6–
1
[a] 35% of 1b was recovered. [b] 2 h of irradiation at 220 °C with
ArBr. [c] Synthesis of 1a only. [d] 37% of 1i was isolated. [e] 35%
of 1h was recovered.
132.3 °C (lit. m.p. 131–133 °C). H NMR (250 MHz, CDCl3): δ =
8.10 (dt, J = 6.8, 1.1 Hz, 1 H), 8.00–7.91 (m, 2 H), 7.85 (s, 1 H),
7.63 (dq, J = 9.1, 1.0 Hz, 1 H), 7.50–7.39 (m, 2 H), 7.38–7.28 (m,
1 H), 7.16 (ddd, J = 9.1, 6.8, 1.3 Hz, 1 H), 6.76 (td, J = 6.8, 1.2 Hz,
1 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 146.0, 145.8, 133.9,
for 2r. In this case, the reactivity of the C3 position dropped
completely. It is worth noting that during the reaction, ex- 128.8, 128.1, 126.2, 125.7, 124.7, 117.7, 112.5, 108.2 ppm.
4
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Synthesis of Various 2,3-Diarylimidazo[1,2-a]pyridines
2-(2-Methoxyphenyl)imidazo[1,2-a]pyridine (1b):[19] Brown solid,
136.4, 133.8, 128.6, 128.6, 127.8, 127.2, 126.3, 118.8, 112.1, 109.2,
m.p. 91.0–93.9 °C (lit. m.p. 94–96 °C). 1H NMR (250 MHz, 103.2, 70.8 ppm.
CDCl3): δ = 8.41 (dd, J = 7.7, 1.8 Hz, 1 H), 8.18 (s, 1 H), 8.09 (br.
7-Methyl-2-phenylimidazo[1,2-a]pyridine (1j):[19] Recrystallized
d, J = 6.8 Hz, 1 H), 7.61 (br. d, J = 9.1 Hz, 1 H), 7.30 (ddd, J =
8.2, 7.3, 1.8 Hz, 1 H), 7.19–7.05 (m, 2 H), 6.99 (dd, J = 8.2, 1.2 Hz,
1 H), 6.71 (ddd, J = 6.8, 6.7, 1.2 Hz, 1 H), 3.98 (s, 3 H) ppm. 13C
NMR (62.5 MHz, CDCl3): δ = 156.8, 144.5, 141.3, 128.9, 128.7,
125.7, 124.5, 122.5, 121.1, 117.4, 112.6, 112.0, 110.5, 55.5 ppm.
from EtOH. White solid, m.p. 164.3–164.7 °C (lit. m.p. 165–
1
167 °C). H NMR (250 MHz, CDCl3): δ = 7.93 (br. d, J = 7.1 Hz,
3 H), 7.73 (s, 1 H), 7.46–7.26 (m, 4 H), 6.56 (br. d, J = 7.0 Hz, 1
H), 2.37 (s, 3 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 146.2,
145.6, 135.6, 134.0, 128.7, 127.9, 126.0, 124.9, 116.0, 115.1, 107.6,
21.5 ppm.
2-(3-Methoxyphenyl)imidazo[1,2-a]pyridine (1c):[20] Orange solid,
1
m.p. 62.4–63.5 °C. H NMR (250 MHz, CDCl3): δ = 8.07 (br. d, J
7-Chloro-2-phenylimidazo[1,2-a]pyridine (1k):[25] Beige solid, m.p.
181.5–183.0 °C (lit. m.p. 180–181 °C). 1H NMR (250 MHz,
CDCl3): δ = 7.98 (dd, J = 7.2, 0.9 Hz, 1 H), 7.95–7.88 (m, 2 H),
7.78 (d, J = 0.7 Hz, 1 H), 7.61 (dd, J = 1.9, 0.9 Hz, 1 H), 7.47–7.38
(m, 3 H), 7.37–7.29 (m, 1 H), 6.74 (dd, J = 7.2, 2.1 Hz, 1 H) ppm.
13C NMR (62.5 MHz, CDCl3): δ = 146.9, 145.5, 133.4, 131.1,
128.9, 128.4, 126.2, 125.9, 116.4, 114.2, 108.3 ppm.
= 6.6 Hz, 1 H), 7.82 (s, 1 H), 7.63 (d, J = 9.1 Hz, 1 H), 7.58–7.54
(m, 1 H), 7.50 (br. d, J = 7.6 Hz, 1 H), 7.33 (dd, J = 7.7, 7.7 Hz,
1 H), 7.14 (br. dd, J = 7.8, 6.7 Hz, 1 H), 6.88 (br. dd, J = 8.2,
2.6 Hz, 1 H), 6.74 (dd, J = 7.1, 6.1 Hz, 1 H), 3.88 (s, 3 H) ppm.
13C NMR (62.5 MHz, CDCl3): δ = 160.1, 145.7, 145.7, 135.3,
129.8, 125.7, 124.8, 118.6, 117.6, 114.3, 112.6, 111.1, 108.5,
55.5 ppm.
6-Methyl-2-phenylimidazo[1,2-a]pyridine (1l):[26] Beige solid, m.p.
172.0–172.5 °C (lit. m.p. 171–173 °C). 1H NMR (250 MHz,
CDCl3): δ = 7.99–7.98 (m, 2 H), 7.86–7.78 (m, 1 H), 7.75–7.69 (m,
1 H), 7.51 (d, J = 9.2 Hz, 1 H), 7.46–7.37 (m, 2 H), 7.35–7.26 (m,
1 H), 6.97 (dd, J = 9.2, 1.9 Hz, 1 H), 2.27 (s, 3 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 145.6, 144.8, 134.1, 128.8, 127.9, 126.0,
123.4, 122.0, 116.9, 107.9, 18.2 ppm.
2-(4-Methoxyphenyl)imidazo[1,2-a]pyridine (1d):[7c] Recrystallized
from EtOH. Beige solid, m.p. 136.8–137.4 °C (lit. m.p. 135–136 °C).
1H NMR (250 MHz, CDCl3): δ = 8.06 (br. d, J = 6.7 Hz, 1 H),
7.88 (br. d, J = 8.9 Hz, 2 H), 7.74 (s, 1 H), 7.60 (d, J = 9.1 Hz, 1
H), 7.13 (ddd, J = 9.0, 6.8, 1.3 Hz, 1 H), 7.96 (br. d, J = 8.8 Hz, 2
H), 6.73 (ddd, J = 6.8, 6.6, 1.1 Hz, 1 H), 3.84 (s, 3 H) ppm. 13C
NMR (62.5 MHz, CDCl3): δ = 159.7, 145.8, 145.7, 127.4, 126.6,
125.6, 124.6, 117.4, 114.2, 112.3, 107.3, 55.4 ppm.
2-Phenyl-6-(trifluoromethyl)imidazo[1,2-a]pyridine (1m): Yellow
1
solid, m.p. 191.5–192.7 °C. H NMR (250 MHz, CDCl3): δ = 8.49
2-(4-Chlorophenyl)imidazo[1,2-a]pyridine (1e):[7c] Recrystallized
(br. s, 1 H), 8.00–7.97 (m, 1 H), 7.94 (br. s, 2 H), 7.72 (br. d, J =
9.5 Hz, 1 H), 7.51–7.41 (m, 2 H), 7.41–7.35 (m, 1 H), 7.32 (dd, J
= 9.5, 1.8 Hz, 1 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 148.0,
145.5, 133.1, 129.0, 128.8, 126.4, 125.8, 124.7 (q, J = 5.8 Hz), 121.5,
120.7 (q, J = 2.7 Hz), 118.3, 117.0 (q, J = 33.9 Hz), 109.3 ppm.
HRMS (ESI): m/z [M + H]+ calcd. for C14H10F3N2 263.079059;
found 263.079503.
from MeOH. White solid, m.p. 206.5–207.0 °C (lit. m.p. 207–
209 °C). H NMR (250 MHz, CDCl3): δ = 8.06 (br. d, J = 6.7 Hz,
1
1 H), 7.86 (br. d, J = 8.5 Hz, 2 H), 7.79 (s, 1 H), 7.60 (d, J = 9.1 Hz,
1 H), 7.38 (br. d, J = 8.5 Hz, 2 H), 7.15 (br. dd, J = 9.1, 6.7 Hz, 1
H), 6.75 (br. dd, J = 6.8, 6.7 Hz, 1 H) ppm. 13C NMR (62.5 MHz,
CDCl3): δ = 145.8, 144.7, 133.8, 132.4, 129.0, 127.3, 125.7, 125.0,
117.6, 112.7, 108.3 ppm.
6-Bromo-2-phenylimidazo[1,2-a]pyridine (1n):[27] Recrystallized
from EtOH. Beige solid, m.p. 200.0–201.0 °C (lit. m.p. 201–202 °C).
1H NMR (250 MHz, CDCl3): δ = 8.24 (dd, J = 1.9, 0.8 Hz, 1 H),
7.96–7.88 (m, 2 H), 7.80 (s, 1 H), 7.53 (d, J = 9.5 Hz, 1 H), 7.48–
7.39 (m, 2 H), 7.38–7.29 (m, 1 H), 7.22 (dd, J = 9.5, 1.8 Hz, 1
H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 146.7, 144.2, 133.3,
128.9, 128.5, 128.3, 126.2, 125.7, 118.2, 108.4, 107.1 ppm.
2-(4-Fluorophenyl)imidazo[1,2-a]pyridine (1f):[21] Recrystallized
from MeOH. White solid, m.p. 163.1–163.4 °C (lit. m.p. 165–
166 °C). 1H NMR (250 MHz, CDCl3): δ = 8.10 (dt, J = 6.8, 1.2 Hz,
1 H), 7.96–7.84 (m, 2 H), 7.79 (br. s, 1 H), 7.61 (ddd, J = 9.1, 1.1,
1.0 Hz, 1 H), 7.21–7.05 (m, 3 H), 6.77 (ddd, J = 6.8, 6.8, 1.2 Hz, 1
H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 164.8, 160.9, 145.5 (d,
J = 45.5 Hz), 130.2 (d, J = 3.1 Hz), 127.8 (d, J = 8.1 Hz), 125.7,
124.9, 117.7, 155.8 (d, J = 21.6 Hz), 112.6, 107.9 ppm.
2-(4-Nitrophenyl)imidazo[1,2-a]pyridine (1g):[22] Recrystallized from
EtOH. Yellow solid, m.p.Ͼ 260 °C (lit. m.p. 266–267 °C). 1H NMR
(250 MHz, CDCl3): δ = 8.30 (br. d, J = 9.0 Hz, 2 H), 8.18–8.08 (m,
3 H), 8.00 (d, J = 0.8 Hz, 1 H), 7.66 (ddd, J = 9.2, 1.0, 1.0 Hz, 1
H), 7.29–7.19 (m, 1 H), 6.85 (ddd, J = 6.9, 6.8, 1.2 Hz, 1 H) ppm.
13C NMR (62.5 MHz, [D6]DMSO): δ = 146.5, 145.2, 142.0, 140.5,
127.3, 126.3, 125.9, 124.2, 117.0, 112.9, 111.7 ppm.
8-Methyl-2-phenylimidazo[1,2-a]pyridine (1h):[23] Recrystallized
from EtOH. Beige solid, m.p. 104.9–105.2 °C (lit. m.p. 105–106 °C).
1H NMR (250 MHz, CDCl3): δ = 8.02–7.90 (m, 3 H), 7.81 (s, 1
H), 7.49–7.39 (m, 2 H), 7.37–7.27 (m, 1 H), 6.93 (d, J = 6.8 Hz, 1
H), 6.65 (dd, J = 6.8, 6.7 Hz, 1 H), 2.70 (s, 3 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = . 146.3, 145.3, 134.2, 128.8, 127.8, 128.7,
126.2, 123.5, 123.3, 112.4, 108.7, 17.2 ppm.
6-Chloro-2-phenylimidazo[1,2-a]pyridine (1o):[7c] White solid, m.p.
199.7–202.4 °C (lit. m.p. 204–206 °C). 1H NMR (250 MHz,
CDCl3): δ = 8.12 (dd, J = 2.0, 0.9 Hz, 1 H), 7.95–7.88 (m, 2 H),
7.78 (br. s, 1 H), 7.58 (br. d, J = 9.6 Hz, 1 H), 7.47–7.39 (m, 2 H),
7.38–7.29 (m, 1 H), 7.12 (dd, J = 9.6, 2.0 Hz, 1 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 146.8, 144.1, 133.2, 128.9, 128.4, 126.3,
126.2, 123.5, 120.7, 117.9, 108.6 ppm.
Methyl 2-Phenylimidazo[1,2-a]pyridine-6-carboxylate (1p):[28] Beige
solid, m.p. 180.5–181.4 °C (lit. m.p. 180–181 °C). 1H NMR
(250 MHz, CDCl3): δ = 8.92 (br. s, 1 H), 8.01–7.95 (m, 2 H), 7.94
(s, 1 H), 7.73 (dd, J = 9.5, 1.6 Hz, 1 H), 7.63 (d, J = 9.6 Hz, 1 H),
7.51–7.32 (m, 3 H), 3.97 (s, 3 H) ppm. 13C NMR (62.5 MHz,
CDCl3): δ = 165.5, 147.8, 146.3, 133.2, 129.9, 129.0, 128.6, 126.4,
124.5, 116.9, 116.6, 109.6, 52.6 ppm.
General Procedure for the Synthesis of 2a–2w: 2-Aminopyridine
(1 mmol), α-bromo ketone (1 mmol) and NaHCO3 (1 mmol) were
8-(Benzyloxy)-2-phenylimidazo[1,2-a]pyridine (1i):[24] Yellow solid,
m.p. 130.9–133.6 °C (lit. m.p. 132–135 °C). 1H NMR (250 MHz, dissolved in PEG400 (8 mL) in a sealed vial before being irradiated
CDCl3): δ = 8.06–7.98 (m, 2 H), 7.84 (s, 1 H), 7.75 (dd, J = 6.7, for 10 min at 120 °C. Then ArBr (1.5 mmol), KOAc (4 mmol) and
1.0 Hz, 1 H), 7.52 (d, J = 6.8 Hz, 2 H), 7.46–7.29 (m, 6 H), 6.59
(dd, J = 7.7, 6.7 Hz, 1 H), 6.43 (d, J = 7.5 Hz, 1 H), 5.43 (s, 2
Pd(OAc)2 (1 mol-%) were added and the reaction mixture was irra-
diated for 1 or 2 h at 220 °C. AcOEt (10 mL) and a saturated solu-
H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 147.9, 145.0, 140.3, tion of NaHCO3 (10 mL) were added to the reaction mixture. The
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O42079
/KAP1
Date: 12-06-14 17:05:48
Pages: 9
M.-A. Hiebel, Y. Fall, M.-C. Scherrmann, S. Berteina-Raboin
FULL PAPER
resulting aqueous layer was extracted with AcOEt (3ϫ 5 mL). The
7.96–7.90 (m, 1 H), 7.87–7.79 (m, 2 H), 7.69 (br. d, J = 9.1 Hz, 1
combined organic phase was then washed with a saturated solution
H), 7.64–7.53 (m, 3 H), 7.49–7.41 (m, 2 H), 7.30–7.21 (m, 1 H),
of NaHCO3 (5ϫ 5 mL) and dried with MgSO4. After filtration 6.79 (br. dd, J = 6.9, 6.9 Hz, 1 H) ppm. 13C NMR (62.5 MHz,
and concentration under reduced pressure the crude product was
purified by flash chromatography with a mixture of ethyl acetate
and petroleum ether (10–40%) as eluent or recrystallization when
specified to provide the expected product.
CDCl3): δ = 146.9, 145.2, 141.0, 140.0, 130.7, 130.0, 129.7, 129.1,
128.4, 125.7, 123.7, 123.7, 123.1, 117.9, 113.0 ppm.
2-Phenyl-3-(m-tolyl)imidazo[1,2-a]pyridine (2i):[13a] Beige solid, m.p.
1
163.1–163.4 °C. H NMR (250 MHz, CDCl3): δ = 7.93 (ddd, J =
2,3-Diphenylimidazo[1,2-a]pyridine (2a):[6] White solid, m.p. 145.3–
6.9, 1.2, 1.2 Hz, 1 H), 7.73–7.63 (m, 3 H), 7.41 (ddd, J = 7.3, 7.2,
1
148.1 °C (lit. m.p. 149–150 °C). H NMR (250 MHz, CDCl3): δ = 1.2 Hz, 1 H), 7.35–7.12 (m, 7 H), 6.71 (ddd, J = 6.9, 6.8, 1.2 Hz, 1
7.99 (d, J = 6.9 Hz, 1 H), 7.77–7.65 (m, 3 H), 7.60–7.42 (m, 5 H),
H), 2.40 (s, 3 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 144.8,
7.37–7.17 (m, 4 H), 6.77 (ddd, J = 6.8, 6.8, 1.2 Hz, 1 H) ppm. 13C 142.3, 139.4, 134.4, 131.3, 129.9, 129.8, 129.6, 128.4, 128.1, 128.0,
NMR (62.5 MHz, CDCl3): δ = 144.8, 142.4, 134.2, 130.7, 129.9, 128.0, 127.5, 124.7, 123.5, 121.4, 117.6, 112.3, 21.6 ppm.
129.6, 128.9, 128.3, 128.1, 128.0, 127.5, 124.7, 123.3, 121.1, 117.5,
112.9 ppm.
3-(3-Nitrophenyl)-2-phenylimidazo[1,2-a]pyridine (2j): Recrystallized
from EtOH. Yellow solid, m.p. 165.8–167.5 °C. 1H NMR
2-(2-Methoxyphenyl)-3-phenylimidazo[1,2-a]pyridine (2b):[6] Beige
(250 MHz, CDCl3): δ = 8.38 (br. s, 1 H), 8.32 (d, J = 8.1 Hz, 1 H),
solid, m.p. 121.8–123.0 °C (lit. m.p. 124–125 °C). 1H NMR 7.99 (d, J = 6.9 Hz, 1 H), 7.80–7.64 (m, 3 H), 7.59 (dd, J = 6.7,
(250 MHz, CDCl3): δ = 8.24 (ddd, J = 7.0, 1.2, 1.1 Hz, 1 H), 7.72
(ddd, J = 9.1, 1.2, 1.1 Hz, 1 H), 7.63 (dd, J = 7.5, 1.8 Hz, 1 H),
3.0 Hz, 2 H), 7.39–7.21 (m, 5 H), 6.83 (dd, J = 6.9, 6.7 Hz, 1
H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 149.1, 145.5, 144.0,
7.48–7.31 (m, 5 H), 7.21 (ddd, J = 9.1, 6.7, 1.3 Hz, 1 H), 7.02 (ddd, 137.1, 133.6, 131.9, 130.8, 128.6, 128.4, 128.2, 125.5, 125.2, 123.6,
J = 7.5, 7.4, 1.1 Hz, 1 H), 6.84 (dd, J = 8.3, 1.0 Hz, 1 H), 6.78
(ddd, J = 6.9, 6.8, 1.2 Hz, 1 H), 3.37 (s, 3 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 156.8, 144.9, 140.8, 132.2, 130.9, 129.3,
129.2, 128.9, 127.9, 124.2, 123.8, 123.2, 122.8, 120.7, 118.0, 112.3,
111.0, 54.8 ppm.
122.8, 118.5, 118.1, 113.2 ppm. HRMS (ESI): m/z [M + H]+ calcd.
for C19H14N3O2 316.108053; found 316.108243.
2-Phenyl-3-(p-tolyl)imidazo[1,2-a]pyridine (2k):[6] Beige solid, m.p.
133.2–135.6 °C (lit. m.p.136–137 °C). 1H NMR (250 MHz,
CDCl3): δ = 7.92 (br. d, J = 7.0 Hz, 1 H), 7.74–7.62 (m, 3 H), 7.32
(s, 4 H), 7.29–7.21 (m, 3 H), 7.21–7.12 (m, 1 H), 6.69 (br. dd, J =
6.9, 6.8 Hz, 1 H), 2.45 (s, 3 H) ppm. 13C NMR (62.5 MHz, CDCl3):
δ = 144.8, 142.3, 138.9, 132.2, 130.7, 130.4, 128.3, 128.1, 127.5,
126.9, 124.6, 123.4, 121.2, 117.6, 112.2, 21.6 ppm.
3-(4-Methoxyphenyl)-2-phenylimidazo[1,2-a]pyridine (2l):[6] White
solid, m.p. 125.0–126.1 °C (lit. m.p. 129–130 °C). 1H NMR
(250 MHz, CDCl3): δ = 7.91 (ddd, J = 6.9, 1.2, 1.2 Hz, 1 H), 7.73–
7.63 (m, 3 H), 7.37 (br. d, J = 8.8 Hz, 2 H), 7.33–7.24 (m, 3 H),
7.24–7.14 (m, 1 H), 7.06 (br. d, J = 8.8 Hz, 2 H), 6.72 (ddd, J =
6.8, 1.2, 1.2 Hz, 1 H), 3.90 (s, 3 H) ppm. 13C NMR (62.5 MHz,
2-(3-Methoxyphenyl)-3-phenylimidazo[1,2-a]pyridine (2c): Beige
1
solid, m.p. 99.0–100.8 °C. H NMR (250 MHz, CDCl3): δ = 7.94
(d, J = 6.9 Hz, 1 H), 7.68 (d, J = 9.0 Hz, 1 H), 7.60–7.40 (m, 5 H),
7.29–7.22 (dq, J = 4.0, 1.4 Hz, 2 H), 7.22–7.12 (m, 1 H), 6.80 (ddd,
J = 8.0, 2.6, 1.3 Hz, 1 H), 6.76–6.68 (m, 1 H), 3.68 (s, 3 H) ppm.
13C NMR (62.5 MHz, CDCl3): δ = 159.6, 144.8, 142.4, 135.6,
130.9, 130.1, 129.6, 129.4, 129.0, 124.8, 123.4, 121.3, 120.7, 117.7,
114.3, 112.7, 112.4, 55.2 ppm. HRMS (ESI): m/z [M + H]+ calcd.
for C20H17N2O 301.133893; found 301.133540.
2-(4-Methoxyphenyl)-3-phenylimidazo[1,2-a]pyridine (2d):[6] Beige
solid, m.p. 102.0–105.7 °C (lit. m.p. 101–102 °C). 1H NMR CDCl3): δ = 160.1, 144.8, 142.3, 134.5, 134.5, 132.2, 128.4, 128.1,
(250 MHz, CDCl3): δ = 7.92 (br. d, J = 6.6 Hz, 1 H), 7.70–7.56 (m, 127.5, 124.6, 123.5, 122.0, 117.6, 115.2, 112.3, 55.5 ppm.
3 H), 7.55–7.36 (m, 5 H), 7.22–7.10 (m, 1 H), 6.81 (br. d, J =
3-(4-Nitrophenyl)-2-phenylimidazo[1,2-a]pyridine (2m):[30] Yellow
8.7 Hz, 2 H), 6.73–6.62 (m, 1 H), 3.77 (s, 3 H) ppm. 13C NMR
solid, m.p. 157.5–159.0 °C (lit. m.p. 150–152 °C). 1H NMR
(62.5 MHz, CDCl3): δ = 159.2, 144.8, 142.4, 130.8, 130.1, 129.6,
(250 MHz, CDCl3): δ = 8.34 (d, J = 8.8 Hz, 2 H), 8.08 (d, J =
126.4, 128.8, 126.9, 124.5, 123.2, 120.3, 117.4, 113.8, 112.1,
55.3 ppm.
7.3 Hz, 1 H), 7.72 (d, J = 8.8 Hz, 1 H), 7.64 (br. d, J = 8.8 Hz, 2
H), 7.61–7.57 (m, 2 H), 7.37–7.21 (m, 4 H), 6.81 (ddd, J = 6.9, 6.9,
2-(4-Chlorophenyl)-3-phenylimidazo[1,2-a]pyridine (2e): Beige solid,
1.1 Hz, 1 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 147.5, 145.7,
144.5, 136.7, 133.5, 131.1, 128.6, 128.6, 128.2, 125.7, 124.8, 122.9,
118.8, 118.1, 113.2 ppm.
1
m.p. 138.5–139.5 °C. H NMR (250 MHz, CDCl3): δ = 7.93 (dd, J
= 6.7, 1.5 Hz, 1 H), 7.66 (br. d, J = 9.3 Hz, 1 H), 7.60 (br. d, J =
8.7 Hz, 2 H), 7.55–7.35 (m, 5 H), 7.24 (br. d, J = 8.7 Hz, 2 H),
7.21–7.13 (m, 1 H), 6.72 (dd, J = 7.3, 6.9 Hz, 1 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 144.9, 141.4, 133.4, 132.9, 130.7, 129.8,
129.7, 129.4, 129.2, 128.6, 124.6, 125.0, 123.4, 121.3, 117.6,
112.5 ppm. HRMS (ESI): m/z [M + H]+ calcd. for C19H14ClN2
305.084003; found 305.084365.
2-Phenyl-3-[4-(trifluoromethyl)phenyl]imidazo[1,2-a]pyridine (2n):
Beige solid, m.p. 190.4–191.0 °C. 1H NMR (250 MHz, CDCl3): δ
= 8.00 (d, J = 6.9 Hz, 1 H), 7.78 (d, J = 8.1 Hz, 2 H), 7.71 (d, J =
9.1 Hz, 1 H), 7.66–7.55 (m, 4 H), 7.36–7.18 (m, 4 H), 6.79 (dd, J
= 6.7, 6.5 Hz, 1 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 145.3,
143.6, 133.9, 131.0, 130.8 (q, J = 35.4 Hz), 128.5, 128.4, 127.9,
2-(4-Fluorophenyl)-3-phenylimidazo[1,2-a]pyridine (2f):[29] Yellow 126.5 (d, J = 3.7 Hz), 126.2, 125.2, 123.0, 121.9, 119.6, 117.9, 117.5,
solid, m.p. 93.0–95.5 °C (lit. m.p. 104 °C). 1H NMR (250 MHz,
CDCl3): δ = 7.89 (ddd, J = 6.9, 1.2, 1.2 Hz, 1 H), 7.67–7.57 (m, 3
H), 7.53–7.35 (m, 5 H), 7.14 (ddd, J = 9.1, 6.7, 1.3 Hz, 1 H), 6.99–
6.88 (m, 2 H), 6.67 (ddd, J = 6.8, 6.8, 1.2 Hz, 1 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 164.3, 160.4, 144.8, 141.5, 130.4 (J =
33 Hz), 129.7 (J = 8.1 Hz), 129.6, 129.6, 129.0, 124.8, 123.3, 120.8,
117.4, 115.2 (J = 21.4 Hz), 112.3 ppm.
112.8 ppm. HRMS (ESI): m/z [M + H]+ calcd. for C20H14F3N2
339.110360; found 339.110713.
3-(4-Fluorophenyl)-2-phenylimidazo[1,2-a]pyridine (2o): Beige solid,
1
m.p. 146.4–147.4 °C. H NMR (250 MHz, CDCl3): δ = 7.89 (ddd,
J = 6.9, 1.2, 1.1 Hz, 1 H), 7.73–7.60 (m, 3 H), 7.51–7.37 (m, 2 H),
7.37–7.13 (m, 6 H), 6.73 (ddd, J = 6.8, 6.8, 1.2 Hz, 1 H) ppm. 13C
NMR (62.5 MHz, CDCl3): δ = 165.0, 161.1, 145.0, 142.8, 134.1,
132.9, 132.8, 128.4, 128.1, 127.7, 126.0, 129.0, 125.8, 123.2, 120.0,
117.7, 117.1, 113.7, 112.5 ppm. HRMS (ESI): m/z [M + H]+ calcd.
2-(4-Nitrophenyl)-3-phenylimidazo[1,2-a]pyridine (2g):[6] Recrys-
tallized from EtOH. Yellow solid, m.p. 164.8–166.8 °C (lit. m.p.
157–158 °C). 1H NMR (250 MHz, CDCl3): δ = 8.16–8.08 (m, 2 H), for C19H14FN2 289.113553; found 289.113979.
6
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42079
/KAP1
Date: 12-06-14 17:05:49
Pages: 9
Synthesis of Various 2,3-Diarylimidazo[1,2-a]pyridines
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4-(2-Phenylimidazo[1,2-a]pyridin-3-yl)benzaldehyde (2p): Yellow
solid, m.p. 189.7–192.2 °C. 1H NMR (250 MHz, CDCl3): δ = 10.09
(s, 1 H), 8.08 (br. d, J = 6.9 Hz, 1 H), 8.02 (br. d, J = 8.3 Hz, 2 H),
7.73 (br. d, J = 9.0 Hz, 1 H), 7.65 (br. d, J = 8.3 Hz, 2 H), 7.62–
7.54 (m, 2 H), 7.35–7.21 (m, 4 H), 6.81 (ddd, J = 6.9, 6.8, 1.3 Hz,
1 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 191.6, 145.6, 144.0,
136.2, 136.1, 133.8, 131.0, 130.8, 128.6, 128.1, 125.5, 123.1, 119.9,
118.0, 113.0 ppm. HRMS (ESI): m/z [M
C20H15N2O 299.117890; found 299.118222.
+
H]+ calcd. for
8-Methyl-2,3-diphenylimidazo[1,2-a]pyridine (2s): Beige solid, m.p.
122.8–123.7 °C. 1H NMR (250 MHz, CDCl3): δ = 7.83 (d, J =
6.9 Hz, 1 H), 7.72–7.64 (m, 2 H), 7.56–7.39 (m, 5 H), 7.33–7.18 (m,
3 H), 6.98 (br. d, J = 6.8 Hz, 1 H), 6.63 (td, J = 6.9, 6.7, 1.2 Hz, 1
H), 2.70 (s, 3 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 145.4,
142.2, 134.6, 130.8, 130.4, 129.5, 128.8, 128.4, 128.4, 127.6, 127.4,
123.4, 121.6, 121.3, 112.4, 17.3 ppm. HRMS (ESI): m/z [M + H]+
calcd. for C20H17N2 285.138625; found 285.139121.
[3]
[4]
[5]
[6]
[7]
7-Methyl-2,3-diphenylimidazo[1,2-a]pyridine (2t):[31] Beige solid,
1
m.p. 145.9–146.2 °C (lit. m.p. 145.5–146 °C). H NMR (250 MHz,
CDCl3): δ = 7.86 (d, J = 7.0 Hz, 1 H), 7.69 (d, J = 7.6 Hz, 2 H),
7.59–7.39 (m, 6 H), 7.34–7.22 (m, 3 H), 6.57 (d, J = 6.8 Hz, 1 H),
2.43 (s, 3 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 145.3, 142.1,
135.7, 134.4, 130.8, 130.1, 129.5, 128.8, 128.3, 128.1, 127.4, 122.6,
120.6, 115.9, 115.0, 21.4 ppm.
6-Methyl-2,3-diphenylimidazo[1,2-a]pyridine (2v): Beige solid, m.p.
1
196.5–197.7 °C. H NMR (250 MHz, CDCl3): δ = 7.75–7.62 (m, 3
H), 7.58 (dd, J = 9.2, 1.0 Hz, 1 H), 7.53–7.40 (m, 5 H), 7.31–7.19
(m, 3 H), 7.03 (dd, J = 9.2, 1.7 Hz, 1 H), 2.24 (s, 3 H) ppm. 13C
NMR (62.5 MHz, CDCl3): δ = 144.0, 142.4, 134.5, 130.9, 130.3,
129.6, 128.9, 128.3, 128.1, 127.9, 127.4, 122.0, 121.0, 130.9, 117.0,
18.4 ppm. HRMS (ESI): m/z [M + H]+ calcd. for C20H17N2
285.138625; found 285.139062.
[8]
2,3-Diphenyl-6-(trifluoromethyl)imidazo[1,2-a]pyridine (2w): Yellow
1
solid, m.p. 141.9–144.2 °C. H NMR (250 MHz, CDCl3): δ = 8.28
(br. s, 1 H), 7.82–7.73 (m, 1 H), 7.70–7.64 (m, 2 H), 7.59–7.52
(m, 3 H), 7.49–7.43 (m, 2 H), 7.38–7.25 (m, 4 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 144.6, 144.4, 133.5, 130.7, 130.0, 129.7,
128.9, 128.5, 128.2, 128.2, 125.9, 122.4 (q, J = 5.8 Hz), 121.7, 120.6
(q, J = 2.6 Hz), 118.4, 116.9 (q, J = 34.3 Hz) ppm. HRMS (ESI):
m/z [M
339.110664.
+
H]+ calcd. for C20H14F3N2 339.110360; found
[9]
6-Chloro-2,3-diphenylimidazo[1,2-a]pyridine (2x): Beige solid, m.p.
159.9–161.0 °C. 1H NMR (250 MHz, CDCl3): δ = 7.96 (dd, J =
2.0, 0.9 Hz, 1 H), 7.69–7.58 (m, 3 H), 7.56–7.49 (m, 3 H), 7.48–
7.40 (m, 2 H), 7.32–7.23 (m, 3 H), 7.15 (dd, J = 9.5, 2.0 Hz, 1
H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 143.5, 143.2, 133.8,
130.7, 129.9, 129.4, 129.4, 128.5, 128.1, 127.9, 126.1, 121.7, 121.2,
[10]
a) C. Enguehard-Gueiffier, C. Croix, M. Hervet, J.-Y. Kazock,
A. Gueiffier, M. Abarbri, Helv. Chim. Acta 2007, 90, 2349–
2367; b) Z. Bahlaouan, M. Abarbri, A. Duchene, J. Thibonnet,
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+
H]+ calcd. for
C19H14ClN2 305.084003; found 305.084282.
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cle): Copies of 1H and 13C NMR spectra for compounds 1a–1p,
2a–2g, 2i–2p, 2s, 2t and 2v.
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Job/Unit: O42079
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Date: 12-06-14 17:05:49
Pages: 9
M.-A. Hiebel, Y. Fall, M.-C. Scherrmann, S. Berteina-Raboin
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Received: February 14, 2014
Published Online: ᭿
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42079
/KAP1
Date: 12-06-14 17:05:49
Pages: 9
Synthesis of Various 2,3-Diarylimidazo[1,2-a]pyridines
Heterocyclic Chemistry
M.-A. Hiebel, Y. Fall, M.-C. Scherrmann,
S. Berteina-Raboin* .......................... 1–9
Straightforward Synthesis of Various 2,3-
Diarylimidazo[1,2-a]pyridines in PEG400
Medium through One-Pot Condensation
and C–H Arylation
PEG400 was found to be a suitable solvent
for condensation of various 2-amino pyr-
idines with α-bromo ketones. 2-Arylimid-
A combination of the previous conden-
sation with a C–H arylation reaction was
developed to access various 2,3-diarylimid-
azo[1,2-a]pyridines with a reduced amount
of palladium catalyst and no ligand.
Keywords: Synthetic methods / Nitrogen
heterocycles / C–H activation
azo[1,2-a]pyridines were obtained in
a
short time through microwave irradiation.
Eur. J. Org. Chem. 0000, 0–0
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9