A Cu(II)-promoted tandem decarboxylative halogenation and oxidative diamination reaction of 2-aminopyridines with alkynoic acids for the synthesis of 2-haloimidazo[1,2-: A] pyridines

Article abstract of DOI:10.1039/c7ob02014g

A copper-promoted cascade decarboxylative halogenation and oxidative diamination reaction sequence of 2-aminopyridines with alkynoic acids has been developed for the synthesis of 2-haloimidazo[1,2-a]pyridines. In this reaction, two C-N bonds and one C-halogen bond are formed in one pot, generating the desired products in good yields. This is the first report on the synthesis of 2-haloimidazo[1,2-a]pyridine derivatives from alkynoic acids.

Full text of DOI:10.1039/c7ob02014g

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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Cu(II)-promoted Tandem Decarboxylative Halogenation and
Oxidative Diamination Reaction of 2-Aminopyridines with
Alkynoic Acids for the Synthesis of 2-Haloimidazo[1,2-a]pyridines
Received 00th January 20xx,
Accepted 00th January 20xx
Yun Liu,a,b,* Wenhui Wanga Junwen Hana and Jinwei Sunb,*
DOI: 10.1039/x0xx00000x
A
copper-promoted cascade decarboxylative halogention and oxidative diamination reaction sequence of 2-
www.rsc.org/
aminopyridines with alkynoic acids has been developed for the synthesis of 2-haloimidazo[1,2-a]pyridines. In this reaction,
two C-N bonds and one C-halogen bond are formed in one pot, generating the desired products in good yields. This is the
first report for the synthesis of 2- haloimidazo [1,2-a]pyridine derivatives from alkynoic acids.
involve three routes: (i) copper-catalyzed oxidative cyclization
of 2-aminopyridines with halogenated alkynes preprepared by
oxidative halogenation of the terminal alkynes (Scheme 2a);8
Introduction
Imidazo[1,2-a]pyridines are privileged heterocycles1 due to
their remarkable diversified biological activities and their
widespread pharmaceutical use as inhibitors of virus,2 cyclin-
dependent kinase,3 and human rhinovirus4 et al.5 Some of the
representative imidazo[1,2-a]pyridine drugs in current use are
shown in Scheme 1 and it is seen that all of them are 2-
arylated derivatives. Furthermore, imidazo[1,2-a]pyridines
have wide application in material science field.6 Consequently,
the synthesis of imidazo[1,2-a] pyridine derivatives has drawn
much attention in the past decades.7
(ii) copper salt catalyzed cyclization of 2-aminopyridines with
terminal alkynes in the presence of an equimolar amount of
molecular iodine to afford 2-iodoimidazo[1,2-a]pyridines
(Scheme 2b and 2c);9 (iii) chlorocyclization of 2-aminopyridines
with carboxylic acid under metal-free conditions (Scheme
2d).10 However, there are some limitations and inconveniences
to these protocols, such as the necessity of using
prefunctionalized haloalkynes, restricted substituent type at
C3 position of the imidazo[1,2-a]pyridine core, as well as
limited halogen kinds. Therefore, more general synthetic
protocols to these compounds are highly desired.
NMe2
N(n-Pr)2
O
i-Bu
Me
N
O
N
Me
O
N
Me
Cl
A) Previous work
Me
N
Et
Cl
N
R
R
R
N
N
N
Cu(OTf)2 (20 mol%)
CH3CN, O2, 60 o
Zolpidem
R1
C
C
C
X
(a)
(b)
Necopidem
X
I
Alpidem
+
+
n-Pr
N
N
C
Me
N
N
N
NH2
NH2
N
R1
O
S
Me
O
N
R
O
N
Cl
Cu(OAc)2 (10 mol%)
N
R1
CH
N
Zolimidine
I2 (1.0 eq)
DCB, 120 oC, air
Saripidem
R1
Scheme 1 Representative Imidazo[1,2-a]pyridine Drugs
R
R
R
R
N
CuI (10 mol%)
R1
C
CH
+
+
I
N
N
(c)
(d)
I2 (1.5 eq)
CH3CN, 80 oC, O2
N
N
NH2
NH2
2-Haloimidazo[1,2-a]pyridines represent an important class
of imidazo[1,2-a]pyridine derivatives and can be transformed
into the much interested 2-arylated derivatives via cross
coupling reactions. However, there are only a few current
synthetic protocols to these compounds and they mainly
R1
SOCl2 (3.0 eq)
Et3N (2 eq)
N
R1CH2CO2
H
Cl
CHCl3, 90 o
C
R1
B)This work
R
R
N
CuX2 (1.0 eq)
R1
C
C
CO2
H
X
(e)
+
N
CH3CN, air, 90 o
C
N
NH2
R1
Scheme 2 Synthesis of 2-Haloimidazo[1,2-a]pyridines.
In recent years, transition metal-catalyzed decarboxylative
coupling reaction has become a powerful tool to construct
organic molecules.11,12 Among this, alkynoic acid is a common
coupling partner.13 Herein, we report an efficient synthesis of
2-haloimidazo[1,2-a]pyridines via copper-promoted sequential
decarboxylative halogenation and oxidative diamination
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reaction of 2-aminopyridines with alkynoic acids (Scheme 2e). Therefore, the optimal reaction conditions were set to heating
To the best of our knowledge, this is the first report for the 1a (1.5 mmol) and 2a (0.5 mmol) in acetonitrile at 90 oC for 12
synthesis of 2-haloimidazo[1,2-a]pyridines using alkynoic acids h in the presence of 1.0 equiv of CuBr2.
as the starting materials.
With the optimal conditions in hand, we then investigated
the scope of alkynoic acids (Table 2). It showed that either
steric or electronic effect is not important to this reaction and
Results and Discussion
various alkynoic acids
alkynoic acids attached with F, Cl, Me, Et or OMe group at
para-position of benzene ring led to 3b 3f in 72%-86% yields.
2 reacted with 1a well. For instance, aryl
To begin our work, we chose 2-aminopyridine 1a and
phenylpropiolic acid 2a as the model reactants for the
optimization of reaction conditions (Table 1). Initially, by
heating 1a (0.5 mmol), 2a (0.5 mmol), pyridine (1.0 mmol) and
CuBr2 (0.5 mmol) in 1,2-dichloroethane (DCE) at 90 oC in a
sealed tube for 12 h, we got only trace amount of 3a (entry 1).
Using Et3N, K2CO3 or Cs2CO3 as base respectively instead of
pyridine in this reaction did not give any improvement.
However, we found that when the amount of 1a was increased
to 3.0 equiv without adding additional base, 3a was formed in
70% yield (entry 2). Based on this result, other solvents
including DMF, benzene, dioxane and acetonitrile were tried,
and acetonitrile provided the best result (entry 3-6). With
acetonitrile as solvent, we employed 1.0 equiv of CuBr in place
of CuBr2 in the reaction, but only trace amount of 3a was
isolated (entry 7). To reduce the loading of copper salt, we
attempted to use NaBr as bromine source in combination with
0.2 equiv of copper salts, but did not get satisfied result (entry
8-11). Carrying out the reaction without CuBr2, no 3a was
formed (entry 12). Under O2 atmosphere, 3a was obtained in
similar yield as that in the air, while using other oxidants as
TBHP or DTBP led to decreased yields (entry 13-15). Besides,
no better results were obtained by increasing the amount of
CuBr2 or lowering the reaction temperature (entry 16-17).
-
Similarly, aryl alkynoic acids bearing meta- or ortho-
substituent on the benzene ring afforded 3g and 3h in good
yields. Additionally, aliphatic alkynoic acids afforded 3-
unsubstituted and 3-alkylated 2-haloimidazo[1,2-a]pyridines
3i-3l in moderate to good yields which are difficultly prepared
before. Compared to previous examples using terminal alkynes
or halogenated alkynes as reactants which generally led to 2-
haloimidazo[1,2-a]pyridines with aryl or bulky alkyl at C3
position,8,9 this protocol showed more broad product scope
mainly due to the fact that alkynoic acids have higher boiling
point than the corresponding terminal alkynes and haloalkynes,
and are easy to handle at higher reaction temperature.
Table 2 Scope of Alkynoic acidsa,b
Table 1 Optimization of Reaction Conditionsa
Entry Solvent
Copper (eq.)
CuBr2 (1)
CuBr2 (1)
CuBr2 (1)
CuBr2 (1)
CuBr2 (1)
CuBr2 (1)
CuBr (1)
Oxidant (eq.)
Yield (%)b
trace
70
1c
DCE
DCE
air
air
2
3
DMF
air
48
a Conditions: 1a (1.5 mmol), 2 (0.5 mmol), CuBr2 (0.5 mmol), heating in CH3CN (5
mL) at 90 oC for 12 h in a sealed tube. b Isolated yield.
4
C6H6
air
62
5
Dioxane
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
air
51
6
air
78
Next, the scope of 2-aminopyridines was examined. As
shown in table 3, a range of 2-aminopyridine derivatives with
different substituents (F, Cl or Me) on the pyridine ring were
7
air
trace
72
8d
9d
10d
11d
12
13
14
15
16
17e
CuBr2 (0.2)
CuCl2 (0.2)
Cu(OAc)2 (0.2)
Cu(OTf )2 (0.2)
none
air
air
70
air
55
compatible with this reaction, furnishing products 4a-4g in 76%
air
61
to 87% yields. 2-Aminoquinoline was also proven to be good
reactant and afforded 4h in 82% yield. Besides, the reactions
of 2-aminopyridine derivatives with aliphatic alkynoic acids
air
0
CuBr2 (1)
CuBr2 (1)
CuBr2 (1)
CuBr2 (1.2)
CuBr2 (1)
O2
77
TBHP (2)
DTBP (2)
air
28
resulted in products 4i-4p in 48% to 71% yields.
25
Table 3 Scope of 2-Aminopyridinesa,b
78
air
53
R
R
N
a
CuBr2 (1.0 eq)
Conditions: 1a (1.5 mmol), 2a (0.5 mmol), copper salt, oxidant, heating in
Br
R
C
C
CO2H
+
solvent (5 mL) at 90 oC for 12 h in a sealed tube. b Isolated yield. c Using 0.5 mmol
of 1a, adding 1.0 mmol of pyridine. d Adding 2.0 equiv of NaBr. e Heating at 60 oC.
N
CH3CN
90 oC, 12 h
N
NH2
2
R
1
4
2 | J. Name., 2012, 00, 1-3
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F
Me
Cl
N
N
N
N
Br
Br
Br
Br
N
N
N
N
Cl
4b, 82%
4a, 76%
4d
, 87%
4c, 79%
Scheme 3 Gram Scale Synthesis
Me
Me
N
N
N
N
N
N
Br
Br
Br
Br
N
N
pyridine in acetonitrile for 3 h afforded alkyne dimerization
product and bromoalkyne stimutanously (Scheme 4a).
Meanwhile, could generate 3a in 66% yield under the
optimal conditions (Scheme 4b). These result raised the
possibility of bromoalkyne as the reaction intermediate.
Me
Me
6
7
7
OMe
Br
4h, 82%
4g, 83%
4f, 85%
4e, 86%
N
N
N
N
Br
7
Br
N
Br
N
N
N
Cl
Second, no reaction occurred by prolonged heating of 3-
phenylimidazo[1,2-a]pyridine 814 with 2-aminopyridine 1a and
CuBr2 in acetonitrile (Scheme 4c). This illustrated that the
reaction did not proceed via bromination of an intermediate
Me
Cl
Me
Me
4i, 48%
4j, 52%
4k, 56%
4l, 63%
N
N
N
Cl
N
Br
Br
Br
N
Br
N
N
Me
N
Cl
Et
Et
product
8. Finally, the reaction of imidazo[1,2-a]pyridine-2-
Et
n-Pr
4p, 71%
carboxylic acid
9
with CuBr2 and 1a did not lead to 3i, which
4o,68%
4m, 63%
4n, 65%
dispelled the pathway of first diamination of alkynoic acid
followed by decarboxylative bromination (Scheme 4d).
a Conditions: 1 (1.5 mmol), 2 (0.5 mmol), CuBr2 (0.5 mmol), heating in CH3CN (5
mL) at 90 oC for 12 h in a sealed tube. b Isolated yield.
To expand the reaction scope further, we subsequently
surveyed CuCl2-promoted reaction of 2-aminopyridines
alkynoic acids , to synthesize chlorinated products (Table 4).
Pleasingly, aryl propionic acids participating in this reaction
smoothly, resulting in 2-chloroimidazo[1,2-a]pyridines 5a 5e in
68% to 75% yields. Meanwhile, aliphatic propiolic acids gave
1 with
2
-
the chlorinated products 5f-5h in good yields under the
standard conditions.
Table 4 Synthesis of 2-Chloroimidazo[1,2-a]pyridinesa,b
Scheme 4 Control Experiments.
Based on these experimental results and previous
literature,8,15 a plausible mechanism was suggested (Scheme
5). At first, the reaction of alkynoic acid 2a with CuBr2 leads to
intermediate
intermediate
I
, dispelling HBr and CO2 molecules. Next,
is oxidized to the CuIII species II, which
I
undergoes reductive elimination to afford bromoalkyne
situ.16
CuBr2-promoted diamination of generates
intermediate III, which occurs oxidation to CuIII and reductive
7 in
A
7
elimination again to give the final product 3a
.
a Conditions: 1 (1.5 mmol), 2 (0.5 mmol), CuCl2 (0.5 mmol), heating in CH3CN (5
mL) at 90 oC for 12 h in a sealed tube. b Isolated yield.
Noteworthily, this reactions could be carried out on
enlarged gram scale. For example, the reaction of 1a (30 mmol,
2.82 g), 2a (10 mmol, 1.46 g) and CuBr2 (10 mmol, 2.21 g)
under the optimal conditions resulted in 1.87 g 3a, that is, a 69%
yield (Scheme 3).
To shed light on the reaction mechanism, we carried out
several control experiments. First, exposing 2a with CuBr2 and
Scheme 5 Possible Mechanism.
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To demonstrate the utility of these halogenated
Journal Name
79.8, 29.0, 15.1. HRMS (ESI) m/z calcd for C11H9O2 [MꢀH]ꢀ
173.0603, found 173.0603.
imidazo[1,2-a]pyridines, we attempted to synthesize 2-
phenylimidazo[1,2-a]pyridine 10 from 3i via Suzuki reaction. As
we expected, by heating 3i, phenyl boronic acid (1.5 equiv) at
100 oC under Ar atmosphere with 2 mol% of PdCl2(PPh3)2 as 2H), 7.56 (d, J = 8.8 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 161.9,
3-(4-Methoxyphenyl)propiolic acid (2f) Yellow solid, mp 140‒141
oC. 1H NMR (400 MHz, CDCl3) δ 3.84 (s, 3H), 6.89 (d, J = 9.2 Hz,
158.2, 135.3, 114.4, 110.9, 89.8, 79.7, 55.4. HRMS (ESI) m/z calcd
catalyst, we obtained product 10 in 86% yield (Scheme 6).
for C10H7O3 [MꢀH]ꢀ 175.0395, found 175.0406.
3-(3-Methoxyphenyl)propiolic acid (2g) Yellow solid, mp 102‒104
1
oC. H NMR (400 MHz, CDCl3) δ 3.81 (s, 3H), 7.01‒7.04 (m, 1H),
7.1‒7.12 (m, 1H), 7.20 (td, J = 7.6, 1.2 Hz, 1H), 7.29 (t, J = 8.0 Hz,
1H). 13C NMR (100 MHz, CDCl3) δ 159.3, 158.2, 129.8, 125.8,
120.0, 118.1, 117.6, 88.8, 79.8, 55.4. HRMS (ESI) m/z calcd for
C10H7O3 [MꢀH]ꢀ 175.0395, found 175.0395.
Scheme 6 Synthesis of 2-Phenylimidazo[1,2-a]pyridine
3-(2-Chlorophenyl)propiolic acid (2h) Yellow solid, mp 127‒128
Conclusions
1
oC. H NMR (400 MHz, CDCl3) δ 7.29 (td, J = 7.6, 1.2 Hz, 1H),
In summary, we have developed a versatile Cu(II)-promoted 7.40‒7.45 (m, 2H), 7.63 (dd, J = 7.6, 1.6 Hz, 1H). 13C NMR (100
MHz, CDCl3) δ 157.2, 137.6, 134.8, 131.9, 129.6, 126.6, 119.4, 84.7,
84.1. HRMS (ESI) m/z calcd for C9H4ClO2 [MꢀH]ꢀ 178.9900, found
178.9899.
reaction of 2-aminopyridines with alkynoic acids for the
synthesis of 2-haloimidazo[1,2-a]pyridines. In this reaction,
two C-N bond and one C-halogen bond are formed in one pot
and 2-haloimidazo[1,2-a]pyridines were formed in moderate
to high yields. With this protocol, 2-bromo and 2-chloro
imidazo[1,2-a]pyridines with diversified 3-aryl or alkyl group
can be selectively synthesized. We believed that this protocol
may open up a new way to the synthesis of other halogenated
heterocycles using alkynoic acids as coupling partner and
copper halide as halogen source.
General Procedure for the Preparation of 2-Bromo- imidazo[1,2-
a]pyridine 3:
2ꢀAminopyridine 1a (1.5 mmol), alkynoic acid 2 (0.5 mmol) and
CuBr2 (0.5 mmol) were mixed in 5 mL of CH3CN and heated at 90
oC for 12 h in a sealed tube. After completion of the reaction, the
mixture was cooled and separated by flash column chromatography
(ethyl acetate/hexane) on silica gel to afford product 3.
2-Bromo-3-phenylimidazo[1,2-a]pyridine (3a) White solid, mp
150‒152 oC. 1H NMR (400 MHz, CDCl3) δ 6.80 (td, J = 6.8, 1.6 Hz,
1H), 7.20‒7.24 (m, 1H), 7.47‒7.48 (m, 1H), 7.55‒7.60 (m, 5H), 8.11
(d, J = 6.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 144.6, 129.7,
129.3, 129.0, 127.6, 125.2, 123.2, 122.3, 117.3, 113.0. HRMS (ESI)
m/z calcd for C13H10BrN2 [M+H]+ 273.0027, found 273.0020.
Experimental
General: Melting points are uncorrected. 1H NMR spectra were
measured on 400 MHz with CDCl3 as solvent. The chemical shifts
(δ) are reported in parts per million relative to the residual deuterated
solvent signal, and coupling constants (J) are given in Hertz. 13C
NMR spectra were measured on 100 MHz with CDCl3 as solvent.
HRMS (ESI) data were obtained in the electron impact (EI) mode.
2-Bromo-3-(4-fluorophenyl)imidazo[1,2-a]pyridine (3b) White
o
1
solid, mp 162‒163 C. H NMR (400 MHz, CDCl3) δ 6.83 (d, J =
6.8 Hz, 1H), 7.23‒7.27 (m, 3H), 7.52‒7.61 (m, 3H), 8.04 (d, J = 6.8
Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 162.9 (d, J = 248 Hz),
144.6, 131.7 (d, J = 8.0 Hz), 125.2, 123.6, 123.5, 123.0, 122.4,
121.3, 117.4, 116.5 (d, J = 21.7 Hz), 113.2. HRMS (ESI) m/z calcd
for C13H9BrFN2 [M+H]+ 290.9933, found 290.99218.
Alkynoic acids 2 were prepared according to literature 13c.
3-(4-Fluorophenyl)propiolic acid (2b) Yellow solid, mp 130‒132
1
oC. H NMR (400 MHz, CDCl3) δ 7.10 (t, J = 8.4 Hz, 2H), 7.60‒
7.64 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 164.2 (d, J = 253 Hz),
158.0, 135.6 (d, J = 9 Hz), 116.2 (d, J = 22 Hz), 115.3 (d, J = 3 Hz),
87.8, 80.1. HRMS (ESI) m/z calcd for C9H4FO2 [MꢀH]ꢀ 163.0196,
found 163.0195.
2-Bromo-3-(4-chlorophenyl)imidazo[1,2-a]pyridine (3c) White
o
1
solid, mp 178‒179 C. H NMR (400 MHz, CDCl3) δ 6.82 (dd, J =
7.2, 2.0 Hz, 1H), 7.48‒7.60 (m, 6H), 8.07 (d, J = 7.2 Hz, 1H). 13C
NMR (100 MHz, CDCl3) δ 142.9, 134.6, 131.8, 129.6, 129.4, 129.3,
129.2, 126.7, 123.6, 120.1, 116.2, 114.7. HRMS (ESI) m/z calcd for
C13H8BrClN2Na [M+Na]+ 328.9457, found 328.9456.
3-(4-Chlorophenyl)propiolic acid (2c) Yellow solid, mp 169‒170
oC. 1H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 8.4 Hz, 2H), 7.54 (d,
J = 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 156.3, 137.3, 134.3,
129.0, 117.7, 86.7, 80.9. HRMS (ESI) m/z calcd for C9H4ClO2 [Mꢀ
H]ꢀ 178.9900, found 178.9893.
2-Bromo-3-p-tolylimidazo[1,2-a]pyridine (3d) Colorless oil. 1H
NMR (400 MHz, CDCl3) δ 2.45 (s, 3H), 6.79 (t, J = 6.8 Hz, 1H),
7.21 (t, J = 8.0 Hz, 1H), 7.35 (d, J = 7.6 Hz, 2H), 7.45 (d, J = 8.0 Hz,
2H), 7.58 (d, J = 9.2 Hz, 1H), 8.09 (d, J =7.2 Hz, 1H). 13C NMR
(100 MHz, CDCl3) δ 144.5, 139.1, 129.9, 129.6, 125.0, 124.6, 123.3,
122.3, 122.1, 117.3, 112.9, 21.5. HRMS (ESI) m/z calcd for
C14H12BrN2 [M+H]+ 287.0184, found 287.0182.
3-(p-Tolyl)propiolic acid (2d) Yellow solid, mp 150‒152 oC. 1H
NMR (400 MHz, CDCl3) δ 2.39 (s, 3H), 7.19 (d, J = 8.0 Hz, 2H),
8.50 (d, J = 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 158.5,
141.9, 133.3, 129.4, 116.0, 89.5, 79.9, 21.8. HRMS (ESI) m/z calcd
for C10H7O2 [MꢀH]ꢀ 159.0446, found 159.0430.
2-Bromo-3-(4-ethylphenyl)imidazo[1,2-a]pyridine (3e) Colorless
oil. 1H NMR (400 MHz, CDCl3) δ 1.31 (t, J = 7.6 Hz, 3H), 2.73 (q, J
= 7.6 Hz, 2H), 6.77 (td, J = 6.8, 0.8 Hz, 1H), 7.19 (td, J = 7.6, 0.8
Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.57 (d, J
= 8.8 Hz, 1H), 8.10 (d, J = 7.2 Hz, 1H). 13C NMR (100 MHz,
CDCl3) δ 145.2, 144.3, 129.5, 128.6, 124.9, 124.6, 123.3, 122.2,
3-(4-Ethylphenyl)propiolic acid (2e) Yellow solid, mp 104‒106
oC.1H NMR (400 MHz, CDCl3) δ 1.24 (t, J = 7.6 Hz, 3H), 2.68 (q, J
= 7.6 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H). 13
C
NMR (100 MHz, CDCl3) δ 153.2, 148.0, 133.4, 128.3, 116.2, 89.4,
4 | J. Name., 2012, 00, 1-3
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121.9, 117.1, 112.8, 28.7, 15.3. HRMS (ESI) m/z calcd for 2-Bromo-8-fluoro-3-phenylimidazo[1,2-a]pyridine (4a) White
C15H14BrN2 [M+H]+ 301.0340, found 301.0348.
solid, mp 145‒146 oC. 1H NMR (400 MHz, CDCl3) δ 6.74‒6.76 (m,
1H), 6.92‒6.96 (m, 1H), 7.49‒7.58 (m, 5H), 7.93 (d, J = 7.2 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 150.9 (d, J = 254 Hz), 137.2 (d, J =
28.2 Hz), 129.7, 129.4, 129.3, 127.2, 124.0, 122.3, 119.7, 119.6,
112.2, 112.1, 107.8 (d, J = 26.1 Hz). HRMS (ESI) m/z calcd for
C13H9BrFN2 [M+H]+ 290.9933, found 290.9922.
2-Bromo-3-(4-methoxyphenyl)imidazo[1,2-a]pyridine (3f) White
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solid, mp 111‒112 C. H NMR (400 MHz, CDCl3) δ 3.89 (s, 3H),
6.79 (td, J = 6.8, 1.2 Hz, 1H), 7.08 (d, J = 6.8 Hz, 2H), 7.18‒7.23
(m, 1H), 7.47 (d, J = 6.8 Hz, 2H), 7.58 (d, J = 8.8 Hz, 1H), 8.05 (d, J
= 6.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 160.1, 144.4, 131.2,
124.9, 123.2, 122.1, 119.6, 117.2, 114.7, 112.9, 55.4. HRMS (ESI) 2-Bromo-7-chloro-3-phenylimidazo[1,2-a]pyridine (4b) White
m/z calcd for C14H12BrN2O [M+H]+ 303.0133, found 303.0139.
solid, mp 127‒128 C. H NMR (400 MHz, CDCl3) δ 6.80 (dd, J =
o
1
7.6, 2.0 Hz, 1H), 7.47‒7.60 (m, 6H), 8.03 (d, J = 7.6 Hz, 1H). 13
C
2-Bromo-3-(3-methoxyphenyl)imidazo[1,2-a]pyridine (3g) White
solid, mp 88‒89 oC. 1H NMR (400 MHz, CDCl3) δ 3.86 (s, 3H), 6.89
(td, J = 6.8, 0.8 Hz, 1H), 7.00 (dd, J = 8.0, 2.4 Hz, 1H), 7.10‒7.15
(m, 2H), 7.19‒7.24 (m, 1H), 7.46 (t, J = 8.0 Hz, 1H), 7.58 (d, J = 8.8
NMR (100 MHz, CDCl3) δ 144.2, 131.8, 129.6, 129.4, 129.3, 127.1,
123.6, 122.9, 122.7, 116.1, 114.7. HRMS (ESI) m/z calcd for
C13H9BrClN2 [M+H]+ 306.9638, found 306.9639.
Hz, 1H), 8.15 (d, J = 6.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 2-Bromo-6-chloro-3-phenylimidazo[1,2-a]pyridine (4c) White
o
1
160.1, 144.6, 130.3, 128.8, 125.2, 123.4, 122.2, 122.1, 121.7, 117.3, solid, mp 130‒132 C. H NMR (400 MHz, CDCl3) δ 7.20 (dd, J =
115.3, 114.5, 113.0, 55.4. HRMS (ESI) m/z calcd for C14H12BrN2O 9.6, 1.6 Hz, 1H), 7.51‒7.60 (m, 6H), 8.13 (d, J = 1.2 Hz, 1H). 13C
[M+H]+ 303.0133, found 303.0132.
NMR (100 MHz, CDCl3) δ 142.9, 129.6, 129.5, 129.4, 127.0, 126.5,
123.0, 122.9, 121.6, 121.1, 117.7. HRMS (ESI) m/z calcd for
C13H9BrClN2 [M+H]+ 306.9638, found 306.9646.
2-Bromo-3-(2-chlorophenyl)imidazo[1,2-a]pyridine (3h) White
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solid, mp 105‒106 C. H NMR (400 MHz, CDCl3) δ 6.83 (td, J =
6.8, 0.8 Hz, 1H), 7.25‒7.29 (m, 1H), 7.43‒7.52 (m, 3H), 7.58‒7.67 2-Bromo-8-methyl-3-phenylimidazo[1,2-a]pyridine (4d) White
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(m, 3H). 13C NMR (100 MHz, CDCl3) δ 144.8, 135.4, 133.9, 131.2, solid, mp 147‒148 C. H NMR (400 MHz, CDCl3) δ 2.63 (s, 3H),
130.2, 127.4, 126.7, 125.4, 124.3, 123.3, 120.3, 117.1, 112.8. HRMS 6.72 (t, J = 7.2 Hz, 1H), 7.02 (d, J = 6.8 Hz, 1H), 7.46‒7.56 (m, 5H),
(ESI) m/z calcd for C13H9BrClN2 [M+H]+ 306.9638, found 7.98 (d, J = 6.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 145.0,
306.9646.
129.7, 129.2, 128.9, 127.9, 127.2, 124.1, 122.6, 121.6, 121.1, 113.0,
17.0. HRMS (ESI) m/z calcd for C14H12BrN2 [M+H]+ 287.0184,
found 287.0188.
2-Bromoimidazo[1,2-a]pyridine (3i) White solid, mp 80‒81 oC. 1H
NMR (400 MHz, CDCl3) δ 6.84 (t, J = 6.8 Hz, 1H), 7.19‒7.23 (m,
1H), 7.56 (d, J = 8.8 Hz, 1H), 7.57 (s, 1H), 8.06 (d, J = 6.8 Hz, 1H). 2-Bromo-7-methyl-3-phenylimidazo[1,2-a]pyridine (4e) White
o
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13C NMR (100 MHz, CDCl3) δ 144.9, 125.4, 125.0, 122.1, 117.0, solid, mp 142‒143 C. H NMR (400 MHz, CDCl3) δ 2.41 (s, 3H),
113.2, 111.5. HRMS (ESI) m/z calcd for C7H6BrN2 [M+H]+ 6.63 (d, J = 7.2 Hz, 1H), 7.35 (s, 1H), 7.46‒7.56 (m, 5H), 8.00 (d, J
196.9714, found 196.9717.
= 7.2 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 145.0, 136.4, 129.6,
129.2, 128.8, 127.8, 122.5, 121.8, 121.6, 115.7, 115.6, 21.3. HRMS
(ESI) m/z calcd for C14H12BrN2 [M+H]+ 287.0184, found 287.0181.
2-Bromo-3-methylimidazo[1,2-a]pyridine (3j) White solid, mp
100‒101 oC. 1H NMR (400 MHz, CDCl3) δ 2.46 (s, 3H), 6.87 (t, J =
6.8 Hz, 1H), 7.19 (dd, J = 8.0, 0.8 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 2-Bromo-3-(4-methoxyphenyl)-7-methylimidazo[1,2-a]pyridine
7.83 (d, J = 6.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 144.0, (4f) White solid, mp 146‒147 oC. 1H NMR (400 MHz, CDCl3) δ
124.0, 122.8, 121.7, 117.5, 117.0, 112.7, 8.8. HRMS (ESI) m/z calcd 2.40 (s, 3H), 3.88 (s, 3H), 6.61 (dd, J = 6.8, 1.2 Hz, 1H), 7.06 (dt, J
for C8H8BrN2 [M+H]+ 210.9871, found 201.9879.
= 8.8, 2.0 Hz, 2H), 7.32 (s, 1H), 7.46 (dt, J = 8.8, 2.0 Hz, 2H), 7.93
(d, J = 6.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 159.9, 144.8,
136.0, 131.1, 122.5, 121.6, 119.9, 115.6, 115.4, 114.7, 55.4, 21.3.
HRMS (ESI) m/z calcd for C15H14BrN2O [M+H]+ 317.0290, found
317.0281.
2-Bromo-3-ethylimidazo[1,2-a]pyridine (3k) Colorless oil. 1H
NMR (400 MHz, CDCl3) δ 1.24 (t, J = 7.6 Hz, 3H), 2.94 (q, J = 7.6
Hz, 2H), 6.85 (t, J = 6.8 Hz, 1H), 7.17 (td, J = 8.0, 1.2 Hz, 1H), 7.54
(d, J = 9.2 Hz, 1H), 7.90 (d, J = 6.8 Hz, 1H). 13C NMR (100 MHz,
CDCl3) δ 144.1, 123.9, 122.9, 122.7, 121.0, 117.2, 112.6, 16.8, 11.6. 2-Bromo-6-methyl-3-phenylimidazo[1,2-a]pyridine (4g) White
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HRMS (ESI) m/z calcd for C9H10BrN2 [M+H]+ 225.0027, found solid, mp 107‒109 C. H NMR (400 MHz, CDCl3) δ 2.28 (s, 3H),
225.0029.
7.06 (dd, J = 6.8, 1.2 Hz, 1H), 7.47‒7.50 (m, 2H), 7.55‒7.56 (m,
4H), 7.88 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 143.7, 129.7,
129.2, 128.9, 128.3, 127.9, 122.8, 121.9, 121.8, 120.9, 116.6, 18.3.
HRMS (ESI) m/z calcd for C14H12BrN2 [M+H]+ 287.0184, found
287.0189..
2-Bromo-3-propylimidazo[1,2-a]pyridine (3l) Colorless oil. 1H
NMR (400 MHz, CDCl3) δ 0.99 (t, J = 7.6 Hz, 3H), 1.68 (q, J = 7.6
Hz, 2H), 2.90 (t, J = 7.6 Hz, 2H), 6.85 (td, J = 6.8, 0.8 Hz, 1H),
7.15‒7.19 (m, 1H), 7.54 (d, J = 9.2 Hz, 1H), 7.90 (d, J = 7.2 Hz,
1H). 13C NMR (100 MHz, CDCl3) δ 144.1, 123.9, 122.8, 121.9, 2-Bromo-1-phenylimidazo[1,2-a]quinoline (4h) White solid, mp
121.6, 117.2, 112.6, 25.1, 20.5, 13.7. HRMS (ESI) m/z calcd for 129‒130 oC. 1H NMR (400 MHz, CDCl3) δ 7.21 (td, J = 8.4, 1.2 Hz,
C10H12BrN2 [M+H]+ 239.0184, found 239.0181.
1H), 7.33‒7.36 (m, 2H), 7.47‒7.59 (m, 7H), 7.73 (d, J = 7.6 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 143.7, 133.3, 131.2, 130.8, 129.6,
129.3, 129.2, 128.2, 127.2, 125.5, 124.9, 124.3, 122.8, 116.6. HRMS
(ESI) m/z calcd for C17H12BrN2 [M+H]+ 323.0184, found 323.0180.
General Procedure for the Preparation of 2-Bromoimidazo[1,2-
a]pyridine 4:
2ꢀAminopyridine 1 (1.5 mmol), alkynoic acid 2 (0.5 mmol) and
CuBr2 (0.5 mmol) were mixed in 5 mL of CH3CN and heated at 90
oC for 12 h in a sealed tube. After completion of the reaction, the
mixture was cooled and separated by flash column chromatography
(ethyl acetate/hexane) on silica gel to afford product 4.
2-Bromo-6-chloroimidazo[1,2-a]pyridine (4i) White solid, mp
173‒174 oC. 1H NMR (400 MHz, CDCl3) δ 7.18 (dd, J = 9.6, 2.0 Hz,
1H), 7.51 (d, J = 9.6 Hz, 1H), 7.53 (s, 1H), 8.12 (d, J = 1.6 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 143.3, 126.7, 123.3, 122.8, 121.5,
117.4, 112.0. HRMS (ESI) m/z calcd for C7H5BrClN2 [M+H]+
230.9325, found 230.9324.
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2-Bromo-6-chloro-3-methylimidazo[1,2-a]pyridine (4j) White [M+H]+ 229.0533, found 229.0531. HRMS (ESI) m/z calcd for
solid, mp 181‒183 C. H NMR (400 MHz, CDCl3) δ 2.45 (s, 3H), C13H10ClN2 [M+H]+ 229.0533, found 229.0521.
7.14 (dd, J = 9.2, 2.0 Hz, 1H), 7.48 (d, J = 9.2 Hz, 1H), 7.87 (s, 1H).
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13C NMR (100 MHz, CDCl3) δ 142.6, 125.6, 123.0, 121.5, 121.0,
118.6, 117.6, 9.1. HRMS (ESI) m/z calcd for C8H7BrClN2 [M+H]+
244.9481, found 244.9481.
2-Chloro-8-fluoro-3-phenylimidazo[1,2-a]pyridine (5b) White
solid, mp 137‒138 oC. 1H NMR (400 MHz, CDCl3) δ 6.74‒6.79 (m,
1H), 6.93‒6.98 (m, 1H), 7.47‒7.57 (m, 5H), 7.97 (d, J = 7.2 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 150.8 (d, J = 253 Hz), 135.7 (d, J =
2-Bromo-3,7-dimethylimidazo[1,2-a]pyridine (4k) White solid, 28.4 Hz), 134.0, 129.4, 129.3, 129.2, 126.8, 121.4, 119.7 (d, J = 5.0
mp 155‒157 oC. 1H NMR (400 MHz, CDCl3) δ 2.40 (s, 3H), 2.42 (s, Hz), 112.2 (d, J = 6.7 Hz), 108.1, 107.9. HRMS (ESI) m/z calcd for
3H), 6.70 (dd, J = 6.8, 1.2 Hz, 1H), 7.29 (s, 1H), 7.70 (d, J = 7.2 Hz, C13H9ClFN2 [M+H]+ 247.0438, found 247.0449.
1H). 13C NMR (100 MHz, CDCl3) δ 144.4, 135.2, 122.1, 121.0,
2,7-Dichloro-3-phenylimidazo[1,2-a]pyridine (5c) White solid, mp
186‒187 oC. 1H NMR (400 MHz, CDCl3) δ 6.86 (t, J = 6.8 Hz, 1H),
7.27 (t, J = 7.6 Hz, 1H), 7.51‒7.61 (m, 5H), 8.11 (d, J = 6.8 Hz, 1H).
116.9, 115.4, 115.3, 21.3, 8.8. HRMS (ESI) m/z calcd for C9H10BrN2
[M+H]+ 225.0027, found 225.0029.
2-Bromo-1-methylimidazo[1,2-a]quinoline (4l) White solid, mp 13C NMR (100 MHz, CDCl3) δ 143.4, 134.9, 134.2, 130.6, 129.6,
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105‒107 C. H NMR (400 MHz, CDCl3) δ 2.94 (s, 3H), 7.47‒7.51 125.7, 125.5, 123.0, 118.5, 117.5, 113.3. HRMS (ESI) m/z calcd for
(m, 3H), 7.60‒7.64 (m, 1H), 7.80 (dd, J = 8.0, 1.6 Hz, 1H), 8.35 (d, J C13H9Cl2N2 [M+H]+ 263.0143, found 263.0140.
= 8.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 143.3, 134.3, 129.3,
2,6-Dichloro-3-phenylimidazo[1,2-a]pyridine (5d) White solid,
mp 126‒127 oC. 1H NMR (400 MHz, CDCl3) δ 7.20 (dd, J = 9.6, 2.0
Hz, 1H), 7.48‒7.60 (m, 6H), 8.17 (dd, J = 2.0, 0.8 Hz, 1H). 13C
128.3, 126.3, 124.8, 124.4, 122.0, 121.6, 116.7, 115.6, 14.7. HRMS
(ESI) m/z calcd for C12H10BrN2 [M+H]+ 261.0027, found 261.0027.
2-Bromo-6-chloro-3-ethylimidazo[1,2-a]pyridine (4m) White NMR (100 MHz, CDCl3) δ 141.5, 134.7, 129.4, 129.3, 129.2, 126.6,
solid, mp 129‒131 oC. 1H NMR (400 MHz, CDCl3) δ 1.24 (t, J = 7.6 121.6, 121.1, 120.4, 117.7. HRMS (ESI) m/z calcd for C13H9Cl2N2
Hz, 3H), 2.91 (q, J = 7.6 Hz, 2H), 7.12 (dd, J = 9.6, 2.0 Hz, 1H), [M+H]+ 263.0143, found 263.0136.
7.87 (d, J = 9.6 Hz, 1H), 7.92 (d, J = 1.2 Hz, 1H). 13C NMR (100
2-Chloro-1-phenylimidazo[1,2-a]quinoline (5e) Colorꢀless oil. 1H
MHz, CDCl3) δ 142.4, 125.3, 123.7, 121.2, 120.6, 117.6, 16.8, 11.6.
HRMS (ESI) m/z calcd for C9H9BrClN2 [M+H]+ 258.9638, found
NMR (400 MHz, CDCl3) δ 7.25‒7.28 (m, 1H), 7.36‒7.41 (m, 2H),
7.51‒7.59 (m, 7H), 7.78 (dd, J = 8.0, 1.2 Hz, 1H). 13C NMR (100
258.9630.
MHz, CDCl3) δ 142.4, 134.2, 133.5, 131.3, 131.1, 130.2, 129.5,
2-Bromo-3-ethyl-6-methylimidazo[1,2-a]pyridine (4n) White 129.3, 129.1, 128.2, 127.2, 124.9, 124.4, 122.9, 116.7, 116.6. HRMS
solid, mp 109‒111 oC. 1H NMR (400 MHz, CDCl3) δ 1.23 (t, J = 7.6 (ESI) m/z calcd for C17H12ClN2 [M+H]+ 279.0689, found 279.0682.
Hz, 3H), 2.35 (d, J = 0.8 Hz, 3H), 2.90 (q, J = 7.6 Hz, 2H), 7.01 (dd,
2-Chloro-3-ethylimidazo[1,2-a]pyridine (5f) Colorless oil. 1H
NMR (400 MHz, CDCl3) δ 1.27 (t, J = 7.6 Hz, 3H), 2.96 (q, J = 7.6
Hz, 2H), 6.89 (td, J = 6.8, 0.8 Hz, 1H), 7.19‒7.24 (m, 1H), 7.56 (d, J
= 9.2 Hz, 1H), 7.90 (d, J = 6.8 Hz, 1H). 13C NMR (100 MHz,
CDCl3) δ 142.3, 124.9, 122.9, 120.6, 116.9, 113.2, 16.1, 11.5.
J = 9.2, 1.6 Hz, 1H), 7.43 (d, J = 9.2 Hz, 1H), 7.66 (s, 1H). 13C NMR
(100 MHz, CDCl3) δ 143.1, 127.0, 122.6, 122.3, 120.6, 120.5, 116.5,
18.4, 16.8, 11.7. HRMS (ESI) m/z calcd for C10H12BrN2 [M+H]+
239.0184, found 239.0189.
2-Bromo-1-ethylimidazo[1,2-a]quinoline (4o) White solid, mp HRMS (ESI) m/z calcd for C9H10ClN2 [M+H]+ 181.0533, found
112‒114 oC. 1H NMR (400 MHz, CDCl3) δ 1.39 (t, J = 7.6 Hz, 3H), 181.0533.
3.35 (q, J = 7.6 Hz, 2H), 7.46‒7.50 (m, 3H), 7.62‒7.66 (m, 1H), 7.80
(dd, J = 8.0, 1.6 Hz, 1H), 8.22 (d, J = 8.8 Hz, 1H). 13C NMR (100
2,6-Dichloro-3-ethylimidazo[1,2-a]pyridine (5g) White solid, mp
140‒142 oC.. 1H NMR (400 MHz, CDCl3) δ 1.27 (t, J = 7.6 Hz, 3H),
MHz, CDCl3) δ 143.3, 133.7, 129.4, 128.5, 127.1, 126.3, 124.8,
2.93 (q, J = 7.6 Hz, 2H), 7.16 (dd, J = 9.6, 2.0 Hz, 1H), 7.48 (d, J =
9.6 Hz, 1H), 7.93 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 140.9,
133.5, 125.2, 121.1, 120.6, 117.5, 16.1, 11.4. HRMS (ESI) m/z calcd
124.4, 121.6, 116.8, 115.6, 20.4, 12.9. HRMS (ESI) m/z calcd for
C13H12BrN2 [M+H]+ 275.0184, found 275.0194.
2-Bromo-7-chloro-3-propylimidazo[1,2-a]pyridine (4p) Colorless for C9H9Cl2N2 [M+H]+ 215.0143, found 215.0143.
oil. 1H NMR (400 MHz, CDCl3) δ 0.99 (t, J = 7.6 Hz, 3H), 1.67 (q, J
2-Chloro-3-propylimidazo[1,2-a]pyridine (5h) Colorless oil. 1H
= 7.6 Hz, 2H), 2.88 (t, J = 7.6 Hz, 2H), 6.85 (dd, J = 7.2, 2.0 Hz, 1H),
7.55 (d, J = 2.0 Hz, 1H), 7.82 (d, J = 7.2 Hz, 1H). 13C NMR (100
MHz, CDCl3) δ 143.7, 130.7, 123.1, 122.6, 122.1, 116.0, 114.3, 25.1,
20.5, 13.7. HRMS (ESI) m/z calcd for C10H11BrClN2 [M+H]+
272.9794, found 272.9793.
NMR (400 MHz, CDCl3) δ 0.99 (t, J = 7.6 Hz, 3H), 1.69 (q, J = 7.6
Hz, 2H), 2.90 (t, J = 7.6 Hz, 2H), 6.87 (td, J = 6.8, 0.8 Hz, 1H),
7.18‒7.22 (m, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.90 (d, J = 6.8 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 142.6, 133.3, 124.1, 122.8, 119.0,
117.1, 112.7, 24.5, 20.5, 13.7. HRMS (ESI) m/z calcd for
General Procedure for the Preparation of 2-Chloroimidazo[1,2- C10H12ClN2 [M+H]+ 195.0689, found 195.0699.
a]pyridine 5:
Compound 8 was prepared according to literature 14:
2ꢀAminopyridine 1 (1.5 mmol), alkynoic acid 2 (0.5 mmol) and
3-Phenylimidazo[1,2-a]pyridine (8) Colorless oil. 1H NMR (400
MHz, CDCl3) δ 6.79 (td, J = 6.8, 1.2 Hz, 1H), 7.17‒7.21 (m, 1H),
CuCl2 (0.5 mmol) were mixed in 5 mL of CH3CN and heated at 90
oC for 12 h in a sealed tube. After completion of the reaction, the
7.41 (tt, J = 7.2, 1.6 Hz, 1H), 7.49‒7.56 (m, 4H), 7.67 (dt, J = 8.8,
1.2 Hz, 1H), 7.69 (s, 1H), 8.33 (dt, J = 7.2, 1.2 Hz, 1H). C NMR
mixture was cooled and separated by flash column chromatography
(ethyl acetate/hexane) on silica gel to afford product 5.
3
(100 MHz, CDCl3) δ 145.6, 132.0, 128.8, 127.7, 127.6, 125.3, 123.8,
122.9, 117.8, 112.1.
2-Chloro-3-phenylimidazo[1,2-a]pyridine (5a) Colorless oil. 1H
NMR (400 MHz, CDCl3) δ 6.83 (td, J = 6.8, 1.2 Hz, 1H), 7.22‒7.26
(m, 1H), 7.47‒7.60 (m, 6H), 8.16 (d, J = 6.8 Hz, 1H). 13C NMR (100
MHz, CDCl3) δ 143.3, 133.9, 129.4, 129.2, 128.9, 127.3, 125.2,
123.2, 119.7, 117.4, 113.0. HRMS (ESI) m/z calcd for C13H10ClN2
Procedure for the Preparation of 10:
Imidazo[1,2ꢀa]pyridine 3i (0.2 mmol), phenyl boronic acid (0.3
mmol), PdCl2(PPh3)2 (0.004 mmol) and K3PO4 (0.4 mmol) were
6 | J. Name., 2012, 00, 1-3
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mixed in 2.0 mL of toluene and heated at 100 oC under Ar
atmosphere for 12 h. After completion of the reaction, the mixture
was cooled and separated by flash column chromatography (ethyl
acetate/hexane) on silica gel to afford product 10.
C.-X. Yan, G.-F. Shi and Y. Cheng, J. Org. Chem
7458; c) T. Mutai, H. Tomoda, T. Ohkawa, Y. Yabe and K.
Araki, Angew. Chem. Int. Ed 2008 120, 9522.
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10 X. Xiao, Y. Xie, S. Bai, Y. Deng, H. Jiang and W. Zeng, Org.
Lett 2015 17, 3998.
. 2011, 76,
.
,
7
.
,
2-Phenylimidazo[1,2-a]pyridine (10) White solid, mp 125‒127 oC.
1H NMR (400 MHz, CDCl3) δ 6.76 (td, J = 6.8, 1.2 Hz, 1H), 7.13‒
7.17 (m, 1H), 7.32 (t, J = 7.2 Hz, 1H), 7.43 (t, J = 7.2 Hz, 2H), 7.62
(d, J = 9.2 Hz, 1H), 7.84 (s, 1H), 7.94‒7.96 (m, 2H), 8.09 (d, J = 6.8
Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 146.0, 134.0, 129.0, 128.3,
126.3, 125.9, 125.0, 117.8, 112.7, 108.4. HRMS (ESI) m/z calcd for
C13H11N2 [M+H]+ 195.0922, found 195.0917.
,
.
,
,
.
8
9
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.
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Acknowledgements
.
,
This work was supported by Natural Science Foundation of
China (21571087), Natural science research project of Jiangsu
Higher Education Institutions (17KJB150016), Natural Science
Foundation of Jiangsu Province (BK20170939), Open fund by
Jiangsu Key Laboratory of Atmospheric Environment
Monitoring and Pollution Control (KHK1709) and Project
Funded by the Priority Academic Program Development of
Jiangsu Higher Education Institutions (PAPD).
11 For reviews of metal-catalyzed decarboxylation coupling
reaction, see: a) L. J. Goossen, N. Rodríguez and K. Goossen,
Angew. Chem., Int. Ed
.
2008
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47, 3100; b) W. I. Dzik, P. P.
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2011 40,
Lange and L. J. Goossen, Chem. Sci
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, 3
Rodríguez and L. J. Goossen, Chem. Soc. Rev
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,
5030.
12 For examples of metal-catalyzed decarboxylation coupling
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Rodríguez, Angew. Chem., Int. Ed
Zhang and M. F. Greaney, Angew. Chem., Int. Ed
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