Rhodium(iii)-catalyzed vinylic sp2 C-H bond functionalization: Efficient synthesis of pyrido[1,2-α]benzimidazoles and imidazo[1,2-α]pyridines

Article abstract of DOI:10.1039/c3ob41177j

A simple approach for synthesis of novel aza-fused scaffolds such as pyrido[1,2-α]benzimidazoles and imidazo[1,2-α]pyridines was developed by Rh(iii)-catalyzed direct oxidative coupling between alkenes and unactivated alkynes without an extra directing group. The method would allow a broad substrate scope, providing fused heterocycles with potential biological properties. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3ob41177j

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ARTICLE TYPE
Rhodium(III)-catalyzed Vinylic sp2 C-H Bond Functionalization:
Efficient Synthesis of Pyrido[1,2-α]benzimidazoles and Imidazo[1,2-
α]pyridines †
Lin Dong,*a Ji-Rong Huang,a Chuan-Hua Qu,a Qian-Ru Zhang,a Wei Zhang,a Bo Han, b and Cheng
5
Peng*b
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
DOI: 10.1039/b000000x
Previous work: synthetic strategy based on the formation of the imidazole ring
A simple approach for synthesis of novel aza-fused scaffolds
such as pyrido[1,2-]benzimidazoles and imidazo[1,2-
R
N
NH2
EWG
R1
R1
+
N
N
R2
10 ]pyridines was developed by Rh(III)-catalyzed direct
oxidative coupling between alkenes and unactivated alkynes
without an extra directing group. The method would render a
broad substrate scope, providing fused heterocycles with
potential biological preperties.
R2
R1
H
N
R2
n=0, 1
N
R1
(1)
N
N
R2
This work: synthetic strategy based on the formation of the pyridine ring via
direct vinylic sp2 C-H activation without extra directing group
15 Heterocyclic frameworks are found in a large number of
biologically active compounds.1 The aza-fused scaffolds such as
pyrido[1,2-]benzimidazoles and imidazo[1,2-]pyridines are the
key structural motifs in some drug candidates,1ci including
Rifaximin,1j alpidem,2 zolpidem,3 zolimidine and GSK8123974
20 (Figure 1). The classical synthetic approaches for preparation of
those hetercycles mostly rely on the formation of the imidazole
ring (eq 1).5,6 However, these methods generally suffer from
multiple preparative steps or narrow substrate scope.
R3
R3
R4
R4
R2
R2
[RhCp*Cl2]2
R5
R5
N
N
+
(2)
H
Cu(OAc)2 H2O
toluene
H
N
R1
N
R1
Scheme 1 Synthetic strategy of aza-fused scaffolds
30
Transition-metal-catalyzed organic reactions have been
significantly developed over the past decade because they can
minimize waste formation and pre-functionalize steps via CH
activation.711 Recently, Rh(III)-catalyzed vinylic sp2 CH
activation followed by an annulation with a variety of internal
35 alkynes using directing groups has been used to construct various
heterocycles.8c,8g,12 Based on recent work in our group,13 herein,
we report an efficient construction of pyridines by double CH
activations of C2-H of imidazole ring and sp2 C-H of alkene and
subsequent coupling with internal alkynes without directing
40 groups. Both substituted pyrido[1,2-]benzimidazoles and
imidazo[1,2-]pyridines could be prepared (eq 2).
Results and Discussion
We commenced our investigation with the screening of
reaction conditions between N-vinyl-benzimidazole 1a and
45 diphenylacetylene 2a. Different oxidants have been examined
first. AgOAc gave 3aa in 72% yield (Table 1, entry 1). However,
NaOAc with BQ didn’t work in this reaction (entry 2). Only trace
amount of product was observed when the reaction was carried
out under O2 (entry 3). A fair yield (44%) was isolated when
50 Cu(acac)2 was utilized (entry 4). Pleasingly, Cu(OAc)2 provided
an excellent improvement in 91% yield (entry 5). These results
indicate that the oxidant plays a significant role in reaction
efficiency. In addition, a series of bases were further tested,
including Cs2CO3 and TEA, which did not improve the yield
25 Figure 1 Selected biologically active aza-fused heterocycles
aKey Laboratory of Drug-Targeting and Drug Delivery System of the
Education Ministry, Department of Medicinal Chemistry, West China
School of Pharmacy, Sichuan University, Chengdu 610041, China.
E-mail: dongl@scu.edu.cn.
bState Key Laboratory Breeding Base of Systematic research,
Development and Utilization of Chinese Medicine Resources, School of
Pharmacy, Chengdu University of Traditional Chinese Medicine,
Chengdu, 610075, China
† Electronic Supplementary Information (ESI) available: Experimental
procedures, structural proofs. See http://dx.doi.org/10.1039/b000000x/
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 1

Organic & Biomolecular Chemistry
Page 2 of 7
(entries 6 and 7). Furthermore, the choice of solvent was vital to
the catalytic reaction, since t-AmOH and DMF afforded 3aa in
70% and 14% yield, respectively (entries 8 and 9).
reacted smoothly to produce the complex imidazo[1,2-
]pyridines in moderate to good yields (3la3na).
View Article Online
Table 2 Alkynes scopea
DOI: 10.1039/C3OB41177J
Table 1 Conditions screeninga
[Cp*RhCl2]2 (5 mol %)
Cu(OAc)2 H2O
R2
N
N
+
R1
R1
N
toluene, 110
C
R2
N
1a
2
3
Yield (%)b
5
Entry
Alkynes 2
Entry Additive
Base
/
Solvent
toluene
toluene
toluene
toluene
toluene
toluene
toluene
t-AmOH
DMF
Yieldb (%)
72
2a (R1 = R2 = Ph)
1
2
3
4
5
6
3aa, 91
3ab, 99
3ac, 69c
3ad, 75
3ae, 99
3af, 86
2b (R1 = R2 = p-MePh)
2c (R1 = R2 = p-MeOPh)
2d (R1 = R2 = p-ClPh)
2e (R1 = R2 = 3-Py)
AgOAc
1
2
3
4
5
6
7
8
9
NaOAc/BQ
O2
/
n.r.
/
trace
2f (R1 = R2 = nBu)
Cu(acac)2
/
44
99(91c)
14
N
/
Cu(OAc)2H2O
Cu(OAc)2H2O
Cu(OAc)2H2O
Cu(OAc)2H2O
Cu(OAc)2H2O
N
Ph
Ph
7
N
CsCO3
N
Ph
2g
TEA
81
3ag+3ag', 91(1.85:1)d
/
/
70
N
N
8
nBu
Ph
n-Bu
Ph
14
N
N
a
2h
Ph
nBu
Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), [Cp*RhCl2]2 (5
mol %), additive (0.12 mmol), base (0.12 mmol), solvent (1.0 mL), under
3ah+3ah', 99(1.75:1)d
OEt
OEt
b
OEt
OEt
Ar or O2 (balloon pressure) atmosphere, 110 C. Yields of 3aa were
N
N
9
determined by 1H NMR spectroscopy. c Isolated yield is given.
Ph
Ph
Ph
Ph
N
N
Ph
2i
2j
OEt
EtO
3ai+3ai', 97(2.41:1)d
Having established the optimized reaction conditions, the
substrate scope was examined with respect to various alkynes
(Table 2). The present process showed wide substrate tolerance
10
11
12
13
N
COOEt
OEt
Ph
N
COOEt
3aj, 49e
10 with internal alkynes. Diarylalkynes bearing either electron-
donating or -withdrawing groups reacted without incident to give
good yields (entries 14). Furthermore, the alkynes are not
limited to aryl groups, heteroaryl and alkyl-substituted alkynes
also proceeded smoothly (entries 5 and 6). Unsymmetrical
15 alkynes occurred in high reactivity albeit with moderate
regioselectivity (entries 79). Fortunately, when electron-
deficient alkynes 2j and 2k were applied, pyrido[1,2-
]benzimidazoles 3aj and 3ak could be produced as the sole
isomer due to the strong electronic effect (entries 10 and 11).
20 Surprisingly, the regioselectivity could be reversed by employing
the enyne ester 2l, presumably as a result of the interaction
between the catalyst and the olefin (entry 12). Previous studies on
vinylic sp2 CH activation revealed that the reaction is controlled
by electronic effects while little influence is resulted from steric
25 effects in the alkyne insertion event. However, terminal alkyne
failed to work in this reaction (entry 13).
Next, various substituted imidazoles and other azoles with
diverse N-vinly groups were tested under the optimized
conditions (Table 3). Both alkyl and aryl substituents exhibited
30 good reactivity. -methyl and -phenyl substituted vinyl
substituents could react well with 2a to afford the tri-substituted
pyrido[1,2-]benzimidazole 3ba and 3ca in moderate yield.
Moreover, -substituted vinyl substrates were also tolerated in
this system (3da3ga). Disubstituted vinyl substrate could
35 proceed smoothly under the optimized conditions, and qua-
substituted pyrido[1,2-]benzimidazoles 3ha and 3ia were
obtained with moderate yields. 5,6-dimethyl substituted
benzimidazole 1j with 2a gave the corresponding pyrido[1,2-
]benzimidazole 3ja in 80% yield. Importantly, purine
40 derivatives 1k also lead to the fused heterocycles 3ka in 67%
yield. Substituted-imidazoles exhibited the similar high reactivity,
N
P
OEt
Ph
OEt
N
O
P
2k
OEt
O
3ak, 67
N
N
COOEt
Ph
Ph
Ph
N
N
COOEt
Ph
2l
3al+3al', 76(1:2.71)d
COOEt
H
N.R.
2m
45
a Unless otherwise specified, reactions were carried out by treatment of a
mixture of N-vinyl benzimidazole 1a (0.1 mmol) and alkyne 2 (0.2 mmol)
with [Cp*RhCl2]2 (5 mol %) and Cu(OAc)2H2O (0.12 mmol) in toluene
b
(1 mL) at 110 C under Ar atmosphere for 717 h. Isolated yield. c N-
50 vinyl benzimidazole 1a (0.2 mmol) and alkyne 2c (0.1 mmol) were used.
d
e
Regioselectivity determined by 1H NMR analysis. 2j (4 equiv) was
added to the reaction partially.
Subsequently, we conducted intermolecular competition
55 experiments with different substituted azoles. Aryl sp2 CH
exhibited higher reactivity than vinylic sp2 CH, and the ratio of
1
3aa/3a’a was detected to be 1/1.4 by H NMR analysis (eq 3).
This result was contrary to the early observation on the C(5)-H
oxidative annulations of 2-substituted imidazoles and alkynes, in
60 which the vinylic sp2 CH prevailed over the aryl CH (eq 3’).13b,
14
Those experiments suggested that there were two major rate-
limiting steps had been involved in the reaction: one could be the
formation of the Rh-NHC complex, in which step alkenyl had an
advantage over aryl to assist the transition metal center,
65 furthermore the Rh-NHC was more stable at C2 position with
double vicinal heteroatom than C5 position with single vicinal
heteroatom; another could be activation of the sp2 CH, in which
step the vinylic sp2 CH presented more challenge than aryl sp2
2
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 3 of 7
Organic & Biomolecular Chemistry
CH. In addition, the oxidative annulations were favored for
benzimidazole derivatives more than imidazoles for easier
formation of Rh-NHC complex on the former structure (eq 4).
Competition experiments with different alkynes revealed that the
diarylalkynes had the similar reactivity as the alkyl-substituted
alkynes while electron-donating substituents on the aryl moiety
were beneficial for this reaction (eqs 5, 6).
View Article Online
DOI: 10.1039/C3OB41177J
5
Table 3 Scope of azolesa
Conclusion
In summary, we have successfully developed a Rh(III)-
catalyzed oxidative coupling between vinylic sp2 CH activation
35 and unactivated alkynes without an extra directing group,
providing
complex
pyrido[1,2-]benzimidazoles
and
imidazo[1,2-]pyridines. Our approach exhibits broad substrate
scope and high efficacy to access aza-fused scaffolds. Further
studies on the catalytic mechanism and the application of this
40 method to built biologically active compounds are being
conducted in our laboratory.
2CuOAc
N
Cu(OAc)2
N
Ph
Rh(I)
H
N
H
N
1a
Ph
10
3aa
a Unless otherwise specified, all reactions were carried out by treatment of
a mixture of azole 1 (0.1mmol) and alkyne 2a (0.2 mmol) with
[Cp*RhCl2]2 (5 mol %) and Cu(OAc)2·H2O (0.12 mmol) in toluene (1 mL)
at 110 C under Ar atmosphere for a certain time.
N
HOAc
2Cu(OAc)2
H
CuOAc
N
Rh Cp*
Ph
N
I
[RhCp*Cl2]2
N
V
Ph
CuCl2
15
On the basis of the chemistry of known metal catalyzed CH
bond activation/annulation reactions, a plausible mechanism was
proposed (Scheme 2). The C(2)H bond of benzimidazole is
initially cleaved by Cu(OAc)2 as Lewis acid, then
20 transmetallation between copper acetate intermediate I and the
rhodium catalyst takes place to afford the N-heterocyclic carbene
(NHC) complex II, which could be facilitated by the assistance of
adjacent π system. Then five-membered rhodacycle III is
generated via CH activation of ortho vinylic sp2 CH. Insertion
25 of alkyne 2a into the Rh-C bond of intermediate IV gives seven-
membered rhodacycle V, which would subsequent reductive
elimination to afford the product 3aa and an Rh(I) species, and
the latter can be oxidized by Cu(II) to complete the catalytic cycle.
N
H
Rh OAc
N
N
II Cp*
Rh Cp*
Ph
N
N
Ph
HOAc
IV
Rh
Cp*
N
III
Ph
Ph
2a
Scheme 2 Plausible mechanism
Acknowledgements
45
We are grateful for the financial support from the NSFC
(21202106), Sichuan University Scientific Research Foundation,
Sichuan University “985 project-Science and technology
innovation platform for novel drug development” and the Open
Research Fund from State Key Laboratory of Breeding Base of
50 Systematic Research, Development and Utilization of Chinese
Medicine Resources.
Experimental
General remarks
1
All NMR data were obtained for H at 400 MHz, and for 13C at
55 100 MHz. Chemical shifts were reported in ppm from
tetramethylsilane with the solvent resonance as the internal
standard in CDCl3 or DMSO-d6 solution. ESI HRMS was
recorded on a Bruker Apex-2. Infrared spectra were recorded on a
30
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

Organic & Biomolecular Chemistry
Page 4 of 7
VECTOR 22. UV detection was monitored at 220 nm. TLC was
performed on glass-backed silica plates. Column chromatography 60 h, 99% yield; H NMR (400 MHz, CDCl3): δ 8.59-8.53 (m, 5H),
3,4-di(pyridin-3-yl)benzo[4,5]imidazo[1,2-]pyridine (3ae). 7
1
was performed on silica gel (200-300 mesh), eluting with
methanol, ethyl acetate, methylene dichloride and petroleum
ether (EtOAc/PE or MeOH/DCM). All chemicals were used
without purification as commercially available unless otherwise
noted.
7.98-7.92 (m, 3H), 7.55 (t, J = 8.0 Hz, 1H), 7.48 (d,VJiew= A8r.t0icleHOzn,line
DOI: 10.1039/C3OB41177J
1H), 7.43 (t, J = 7.6 Hz, 1H), 7.37-7.34 (m, 1H), 7.24-7.21 (m,
1H), 7.00 (d, J = 7.2 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3):
 151.5, 150.1, 149.0, 148.9, 147.9, 145.0, 138.6, 137.2, 136.9,
65 128.8, 126.0, 125.4, 124.7, 123.3, 123.1, 121.8, 120.4, 112.8,
110.4 ppm. IR (KBr): ν 3054, 3036, 2923, 1493, 1406, 800, 743,
712 cm-1. ESI HRMS: calcd. for C21H14N4Na 345.1116, found
345.1116.
5
General
Procedure
for
Synthesis
of
pyrido[1,2-
]benzimidazole and imidazo[1,2-]pyridines
10 N-vinyl benzimidazole 1a (14.4 mg, 0.1 mmol, 1.0 equiv),
diphenyl acetylene 2a (35.6 mg, 0.2 mmol, 2.0 equiv),
3,4-dibutylbenzo[4,5]imidazo[1,2-]pyridine (3af). 7 h, 86%
1
[Cp*RhCl2]2 (3.1 mg, 5 mol %, 0.05 equiv) and Cu(OAc)2H2O 70 yield; H NMR (400 MHz, CDCl3): δ 8.20 (d, J = 6.8 Hz, 1H),
(24 mg, 0.12 mmol, 1.2 equiv) were stirred in toluene (1.0 mL)
under Ar at 110 C for 12 h. TLC analyses of the mixture
15 confirmed formation of 3aa. The reaction mixture was
neutralized with K2CO3, and flash chromatography on silica gel
7.96 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.47 (td, J =
8.4, 1.2 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 6.66 (d, J = 7.2 Hz, 1H),
3.11 (t, J = 8.0 Hz, 2H), 2.71 (t, J = 8.0 Hz, 2H), 1.78-1.70 (m,
2H), 1.67-1.59 (m, 2H), 1.55-1.42 (m, 4H), 1.00-0.95(m, 6H)
(EtOAc/PE = 1/10) to give the product 3aa as a yellow solid 75 ppm; 13C NMR (100 MHz, CDCl3):  149.5, 144.5, 140.6, 129.2,
(29.1 mg, 91%).
128.3, 125.0, 121.8, 120.2, 119.6, 113.2, 110.1, 32.8, 32.0, 31.7,
27.4, 23.1, 22.7, 14.1, 14.0 ppm. IR (KBr): ν 2958, 2866, 1638,
1609, 1493, 1466, 764, 739 cm-1. ESI HRMS: calcd. for
C19H24N2+H 281.2018, found 281.2019.
3,4-diphenylbenzo[4,5]imidazo[1,2-]pyridine (3aa). 12 h,
1
20 91% yield; H NMR (400 MHz, CDCl3): δ 8.48 (d, J = 7.2 Hz,
1H), 7.99 (d, J = 8.0 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.52 (t, J
= 7.6 Hz, 1H), 7.44-7.20 (m, 11H), 7.00 (d, J = 7.2 Hz, 1H) ppm; 80 3-methyl-4-phenylbenzo[4,5]imidazo[1,2-]pyridine (3ag). 9 h,
13C NMR (100 MHz, CDCl3):  148.8, 145.1, 139.3, 135.1, 131.0,
129.6, 128.9, 128.1, 128.0, 127.7, 127.4, 125.4, 123.5, 121.0,
25 120.4, 113.7, 110.2 ppm. IR (KBr): ν 3052, 1497, 1482, 1228,
760, 737, 699 cm-1. ESI HRMS: calcd. for C23H16N2+H 321.1392,
found 321.1395.
59.1% yield; 1H NMR (400 MHz, CDCl3): δ 8.32 (d, J = 6.8 Hz,
1H), 7.93 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 8.0, 1H), 7.56-7.45 (m,
6H), 7.33 (t, J = 7.6 Hz, 1H), 6.78 (d, J = 7.2 Hz, 1H), 2.30 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3):  149.0, 144.8, 136.9, 135.5,
85 129.9, 129.0, 128.8, 128.5, 127.9, 125.1, 123.0, 120.5, 120.1,
114.0, 110.0, 20.0 ppm. IR (KBr): ν 3054, 2946, 2916, 1630,
1605, 1488, 1433, 777, 736 cm-1. ESI HRMS: calcd. for
C18H14N2+H 259.1235, found 259.1237.
3,4-di-p-tolylbenzo[4,5]imidazo[1,2-]pyridine (3ab). 7 h, 99%
1
yield; H NMR (400 MHz, CDCl3): δ 8.43 (d, J = 6.8 Hz, 1H),
30 7.98 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.49 (t, J = 8.0
Hz, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.16-
7.06 (m, 6H), 6.97 (d, J = 6.8 Hz, 1H), 2.36 (s, 3H), 2.33 (s, 3H) 90 h, 31.9% yield; H NMR (400 MHz, CDCl3): δ 8.33 (d, J = 6.8
4-methyl-3-phenylbenzo[4,5]imidazo[1,2-]pyridine (3ag’). 9
1
ppm; 13C NMR (100 MHz, CDCl3):  149.1, 145.1, 139.9, 137.2,
137.1, 136.5, 132.3, 130.8, 129.5, 128.9, 128.8, 128.0, 125.2,
35 123.2, 120.8, 120.4, 113.8, 110.1, 21.4, 21.2 ppm. IR (KBr): ν
3052, 3021, 2919, 1481, 1440, 820, 780, 736 cm-1. ESI HRMS:
calcd. for C25H20N2+H 349.1705, found 349.1706.
Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.54-
7.47 (m, 4H), 7.43-7.40 (m, 2H), 7.36 (t, J = 7.6 Hz, 1H), 6.83 (d,
J = 7.2 Hz, 1H), 2.67 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3):
 149.5, 144.7, 140.4, 139.4, 129.1, 128.4, 127.8, 125.4, 124.0,
95 121.8, 120.9, 119.8, 113.4, 110.4, 15.0 ppm. IR (KBr): ν 3056,
2925, 1631, 1602, 1501, 1483, 765, 742, 704 cm-1. ESI HRMS:
calcd. for C18H14N2+H 259.1235, found 259.1236.
3,4-bis(4-methoxyphenyl)benzo[4,5]imidazo[1,2-]pyridine
1
(3ac). 7 h, 69% yield; H NMR (400 MHz, CDCl3): δ 8.42 (d, J
40 = 7.2 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 8.0Hz, 1H),
7.51-7.47 (m, 1H), 7.37-7.34 (m, 3H), 7.14 (d, J = 8.8 Hz, 2H),
3-butyl-4-phenylbenzo[4,5]imidazo[1,2-]pyridine (3ah). 7 h,
63% yield; H NMR (400 MHz, CDCl3): δ 8.37 (d, J = 7.2 Hz,
1
6.97 (d, J = 7.2 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 8.4 100 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.54-7.50
Hz, 2H), 3.82 (s, 3H), 3.79 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3):  158.9, 158.8, 149.2, 145.1, 139.5, 132.3, 131.8, 130.9,
45 129.0, 127.6, 127.4, 125.3, 123.1, 120.8, 120.3, 113.9, 113.8,
113.6, 110.2, 55.2 ppm. IR (KBr): ν 3003, 2961, 2935, 2838,
(m, 2H), 7.47-7.42 (m, 4H), 7.34-7.30 (m, 1H), 6.83 (d, J = 6.8
Hz, 1H), 2.56 (t, J = 8.0 Hz, 2H), 1.59-1.51 (m, 2H), 1.31-1.21
(m, 2H), 0.82 (t, J = 7.6 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3):  149.2, 144.8, 141.8, 135.5, 130.0, 129.0, 128.8, 128.5,
1607, 1248, 1030, 835, 788, 742 cm-1. ESI HRMS: calcd. for 105 127.9, 125.1, 123.4, 120.6, 120.2, 112.8, 110.0, 32.8, 32.5, 22.4,
C25H20N2O2+H 381.1603, found 381.1605.
13.8 ppm. IR (KBr): ν 2953, 2919, 2863, 1631, 1605, 1489, 733,
701 cm-1. ESI HRMS: calcd. for C21H20N2+H 301.1705, found
301.1705.
3,4-bis(4-chlorophenyl)benzo[4,5]imidazo[1,2-]pyridine(3ad).
1
50 7 h, 75% yield; H NMR (400 MHz, CDCl3): δ 8.48 (d, J = 6.8
Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.52 (t,
J = 8.0 Hz, 1H), 7.41-7.31 (m, 5H), 7.26 (d, J = 8.4 Hz, 2H), 7.12 110 36% yield; H NMR (400 MHz, CDCl3): δ 8.33 (d, J = 7.2 Hz,
4-butyl-3-phenylbenzo[4,5]imidazo[1,2-]pyridine (3ah’). 7 h,
1
(d, J = 8.4 Hz, 2H), 6.94 (d, J = 6.8 Hz, 1H) ppm; 13C NMR (100
MHz, CDCl3):  148.3, 145.0, 138.9, 137.4, 133.9, 133.8, 133.3,
55 132.4, 130.9, 128.9, 128.6, 127.1, 125.7, 123.0, 121.4, 120.4,
113.2, 110.3 ppm. IR (KBr): ν 3060, 2924, 1499, 1090, 832, 778,
1H), 8.01 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.55-7.34
(m, 7H), 6.79 (d, J = 6.8 Hz, 1H), 3.07(t, J = 8.0 Hz, 2H), 1.78-
1.70 (m, 2H), 1.34-1.28 (m, 2H), 0.80 (t, J = 7.6 Hz, 3H) ppm;
13C NMR (100 MHz, CDCl3):  140.4, 139.8, 129.1, 128.8, 128.4,
745 cm-1. ESI HRMS: calcd. for C23H14Cl2N2+H 389.0612, found 115 127.7, 125.3, 121.8, 120.8, 119.9, 113.7, 110.3, 31.5, 28.3, 22.7,
389.0612.
13.8 ppm. IR (KBr): ν 3051, 2959, 2927, 2852, 1632, 1602, 1499,
4
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Organic & Biomolecular Chemistry
801, 765, 703 cm-1. ESI HRMS: calcd. for C21H20N2+H 301.1705,
found 301.1706.
3-(diethoxymethyl)-4-phenylbenzo[4,5]imidazo[1,2-
]pyridine (3ai). 7 h, 68.6% yield; 1H NMR (400 MHz, CDCl3):
δ 8.49 (d, J = 7.2 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.91 (d, J =
7.6 Hz, 1H), 7.58-7.47 (m, 6H), 7.39-7.35 (m, 1H), 7.27 (d, J =
7.40 (t, J = 7.6 Hz, 1H), 7.13 (d, J = 7.2 Hz, 1H), 6.49 (d, J =
60 16.0 Hz, 1H), 4.22 (q, J = 7.2 Hz, 2H), 1.29 (t, J = 7.2 Hz, 3H)
ppm; 13C NMR (100 MHz, CDCl3):  166.3, 148.1V,i1ew45A.r2ti,cl1e4O0n.l8in,e
DOI: 10.1039/C3OB41177J
133.5, 132.5, 131.8, 130.8, 129.2, 128.9, 128.5, 125.7, 123.8,
122.0, 121.3, 120.7, 110.3, 107.9, 60.7, 14.2 ppm. IR (KBr): ν
3060, 2988, 1705, 1627, 1285, 1183, 786, 740 cm-1. ESI HRMS:
5
7.6 Hz, 1H), 5.22 (s, 1H), 3.64-3.57 (m, 2H), 3.44-3.37 (m, 2H), 65 calcd. for C22H18N2O2+H 343.1447, found 343.1449.
1.19 (t, J = 7.2 Hz, 6H) ppm; 13C NMR (100 MHz, CDCl3): 
148.1, 144.7, 137.7, 133.9, 130.2, 129.4, 128.9, 128.4, 125.4,
1-methyl-3,4-diphenylbenzo[4,5]imidazo[1,2-]pyridine (3ba).
8 h, 66% yield; H NMR (400 MHz, CDCl3): δ 8.18 (d, J = 8.4
1
10 124.2, 121.3, 120.4, 110.3, 108.9, 99.6, 62.9, 15.1 ppm. IR (KBr):
ν 3056, 2973, 2925, 2872, 1489, 1104, 1059, 739, 700 cm-1. ESI
HRMS: calcd. for C22H22N2O2+H 347.1760, found347.1760.
4-(diethoxymethyl)-3-phenylbenzo[4,5]imidazo[1,2-
Hz, 1H), 7.98 (d, J = 8.0Hz, 1H), 7.50(t, J = 7.6 Hz, 1H), 7.41-
7.38 (m, 2H), 7.35-7.17 (m, 9H), 6.77 (s, 1H), 3.11 (s, 3H) ppm;
70 13C NMR (100 MHz, CDCl3):  149.9, 145.6, 140.2, 139.4, 137.2,
135.6, 131.3, 130.2, 129.6, 128.0, 128.0, 127.5, 127.3, 125.6,
124.9, 120.7, 120.3, 114.4, 114.1, 21.4 ppm. IR (KBr): ν 3049,
2919, 2850, 1632, 1602, 1501, 1440, 763, 733, 698 cm-1. ESI
HRMS: calcd. for C24H18N2+H 335.1548, found 335.1548.
]pyridine (3ai’). 7 h, 28.4% yield; 1H NMR (400 MHz, CDCl3):
15 δ 8.40 (d, J = 7.2 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.86 (d, J =
8.4 Hz, 1H), 7.53-7.42 (m, 6H), 7.35 (t, J = 7.6 Hz, 1H), 6.77 (d,
J = 7.2 Hz, 1H), 5.92 (s, 1H), 3.76-3.70 (m, 2H), 3.50-3.42 (m, 75 1,3,4-triphenylbenzo[4,5]imidazo[1,2-]pyridine (3ca). 12 h,
1
2H), 1.12 (t, J = 7.2 Hz, 6H) ppm; 13C NMR (100 MHz, CDCl3):
 147.0, 145.1, 141.6, 139.3, 129.1, 128.5, 127.9, 127.9, 125.4,
20 124.4, 124.0, 120.9, 120.5, 113.6, 110.0, 100.6, 63.6, 15.1 ppm.
IR (KBr): ν 2973, 2925, 2872, 1635, 1603, 1108, 1062, 739, 699
74% yield; H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 8.4 Hz,
1H), 7.67-7.62 (m, 5H), 7.48 (d, J = 7.2 Hz, 2H), 7.40-7.31 (m,
4H), 7.26-7.23 (m, 5H), 6.97 (t, J = 8.0 Hz, 1H), 6.86 (s, 1H),
6.65 (d, J = 8.4 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): 
cm-1. ESI HRMS: calcd. for C22H22N2O2+Na 369.1579, found 80 149.8, 145.6, 140.0, 139.5, 139.3, 135.5, 134.4, 131.3, 130.0,
369.1579.
ethyl
129.7, 129.4, 129.1, 129.1, 128.1, 128.0, 127.6, 127.3, 126.9,
124.8, 120.3, 120.2, 115.3, 114.5 ppm. IR (KBr): ν 3059, 3034,
1598, 1482, 1450, 1313, 766, 743 cm-1. ESI HRMS: calcd. for
C29H20N2+H 397.1705, found 397.1705.
3-phenylbenzo[4,5]imidazo[1,2-]pyridine-4-
1
25 carboxylate (3aj). 7 h, 49% yield; H NMR (400 MHz, CDCl3):
δ 8.50 (d, J = 7.2 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.94 (d, J =
8.4 Hz, 1H), 7.56-7.41 (m, 7H), 7.28 (d, J = 7.2 Hz, 1H), 4.09 (q, 85 2-methyl-3,4-diphenylbenzo[4,5]imidazo[1,2-]pyridine (3da).
J = 7.2 Hz, 2H), 0.97 (t, J = 7.6 Hz, 3H) ppm; 13C NMR (100
MHz, CDCl3):  167.1, 147.7, 145.2, 135.3, 132.6, 130.1, 129.3,
30 128.9, 128.5, 128.3, 126.0, 123.9, 122.2, 120.9, 110.6, 110.3,
61.5, 13.5 ppm. IR (KBr): ν 3058, 2977, 1712, 1476, 1327, 1230,
10 h, 90% yield; 1H NMR (400 MHz, CDCl3): δ 8.34(s, 1H), 7.94
(d, J = 8.0 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 7.6 Hz,
1H), 7.36 (t, J = 7.6 Hz, 1H), 7.31-7.17 (m, 8H), 7.08 (d, J = 6.8
Hz, 2H), 2.16 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): 148.2,
1137, 1027, 743, 698 cm-1. ESI HRMS: calcd. for 90 144.8, 142.9, 137.9, 135.4, 130.7, 129.7, 129.2, 128.8, 127.9,
C20H16N2O2+Na 339.1109, found 339.1109.
127.8, 127.3, 127.1, 125.1, 121.8, 120.7, 120.3, 120.0, 110.2,
18.6 ppm. IR (KBr): ν 3051, 2958, 2918, 1636, 1600, 1487, 1443,
731, 697 cm-1. ESI HRMS: calcd. for C24H18N2+H 335.1548,
found 335.1548.
diethyl
(3-phenylbenzo[4,5]imidazo[1,2-]pyridin-4-
35 yl)phosphonate (3ak). 7 h, 67% yield; 1H NMR (400 MHz,
CDCl3): δ 8.52 (dd, J = 7.2 , 3.6 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H),
7.94 (d, J = 8.4 Hz, 1H), 7.60-7.58 (m, 2H), 7.54-7.40 (m, 6H), 95 2,3,4-triphenylbenzo[4,5]imidazo[1,2-]pyridine (3ea). 9 h,
4.00-3.92 (m, 2H), 3.89-3.83 (m, 2H), 1.17 (t, J = 7.2 Hz, 6H)
ppm; 13C NMR (100 MHz, CDCl3):  145.1, 137.0, 135.0, 135.0,
40 130.0, 128.8, 127.9, 126.1, 123.5, 123.4, 122.2, 121.1, 112.6,
112.5, 110.7, 62.3, 62.3, 16.1, 16.1 ppm. IR (KBr): ν 2986, 1481,
99% yield; 1H NMR (400 MHz, CDCl3): δ 8.48 (s, 1H), 7.99 (d, J
= 8.0, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.53-7.49 (m, 1H), 7.39-7.35
(m, 3H), 7.31-7.23 (m, 6H), 7.16-7.14 (m, 2H), 7.05-6.99 (m, 3H),
6.90-6.87 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3):  148.1,
1323, 1229, 1048, 1019, 771, 739 cm-1. ESI HRMS: calcd. for 100 145.1, 141.0, 137.6, 137.3, 135.5, 131.0, 130.9, 130.0, 129.3,
C21H21N2O3P+Na 403.1187, found 403.1189.
129.0, 127.9, 127.8, 127.4, 127.3, 127.0, 126.6, 126.6, 125.4,
123.3, 121.0, 120.4, 110.3 ppm. IR (KBr): ν 3056, 3027, 1476,
1319, 1259, 754, 698 cm-1. ESI HRMS: calcd. for C29H20N2+H
397.1705, found 397.1707.
(E)-ethyl
45 yl)acrylate
3-(3-phenylbenzo[4,5]imidazo[1,2-]pyridin-4-
(3al). 12 h, 20.5% yield; 1H NMR (400 MHz,
CDCl3): δ 8.44 (d, J = 6.8 Hz, 1H), 8.21 (d, J = 16.0 Hz, 1H),
8.03 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 105 2-(4-chlorophenyl)-3,4-diphenylbenzo[4,5]imidazo[1,2-
1
16.0 Hz, 1H), 7.58-7.39 (m, 7H), 6.90 (d, J = 6.8 Hz, 1H), 4.24 (q,
J = 7.2 Hz, 2H) , 1.32 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100
50 MHz, CDCl3):  168.0, 146.8, 145.3, 144.8, 138.2, 137.7, 129.7,
128.7, 128.6, 128.3, 125.9, 125.2, 124.6, 121.7, 120.5, 120.3,
]pyridine (3fa). 12 h, 89% yield; H NMR (400 MHz, CDCl3):
δ 8.47 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H),
7.51(t, J = 8.0 Hz, 1H), 7.38 (t, J = 7.2 Hz, 1H), 7.34-7.32 (m,
2H), 7.28-7.19 (m, 5H), 7.10 (t, J = 8.8 Hz, 1H), 7.06-7.02 (m,
113.4, 110.2, 60.3, 14.3 ppm. IR (KBr): ν 3058, 2980, 1706, 1601, 110 3H), 6.93 (d, J = 7.6 Hz, 1H) , 6.87-6.86 (m, 2H) ppm; 13C NMR
1283, 1182, 741, 703 cm-1. ESI HRMS: calcd. for C22H18N2O2+H
343.1447, found 343.1449
(100 MHz, CDCl3):  148.0, 145.2, 140.6, 139.5, 137.0, 135.3,
133.8, 130.9, 129.8, 129.6, 129.1, 129.0, 128.3, 127.9, 127.5,
127.2, 126.9, 125.6, 125.3, 123.4, 121.3, 120.6, 110.3 ppm. IR
(KBr): ν 3057, 3027, 1599, 1469, 1320, 787, 744, 702 cm-1. ESI
55 (E)-ethyl
3-(4-phenylbenzo[4,5]imidazo[1,2-]pyridin-3-
yl)acrylate (3al’). 12 h, 55.5% yield; 1H NMR (400 MHz,
CDCl3): δ 8.42 (d, J = 7.2 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.89 115 HRMS: calcd. for C29H19ClN2+H 431.1315, found 431.1315.
(d, J = 8.0 Hz, 1H), 7.69 (d, J = 16.0 Hz, 1H), 7.57-7.48 (m, 6H),
2-(benzo[d][1,3]dioxol-5-yl)-3,4-diphenylbenzo[4,5]imidazo
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Organic & Biomolecular Chemistry
Page 6 of 7
[1,2-]pyridine (3ga). 8 h, 77% yield; 1H NMR (400 MHz,
6-(benzo[d][1,3]dioxol-5-yl)-7,8-diphenylimidazo[1,2-
CDCl3): δ 8.44 (s, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.0, 60 ]pyridine (3ma). 13 h, 77% yield; 1H NMR (400 MHz, CDCl3):
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1H), 7.49 (t, J = 8.0 Hz, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.33-7.31
(m, 2H), 7.28-7.21 (m, 3H), 7.05-7.03 (m, 3H), 6.89-6.87 (m, 2H),
6.68 (d, J = 8.0 Hz, 1H), 6.63 (dd, J = 8.0, 1.2 Hz, 1H), 6.56 (d, J
= 1.2 Hz, 1H), 5.90 (s, 2H) ppm; 13C NMR (100 MHz, CDCl3): 
δ 8.14 (s, 1H), 7.66 (d, J = 13.2 Hz, 2H), 7.2D8O-7I.:1190.(1m03,95/HC3),O7B.40131-77J
7.00 (m, 3H), 6.87-6.84 (m, 2H), 6.64 (d, J = 8.0 Hz, 1H), 6.57
(dd, J = 8.0, 1.6 Hz, 1H), 6.51 (d, J = 1.2 Hz, 1H), 5.89 (s, 2H)
ppm; 13C NMR (100 MHz, CDCl3):  147.1, 146.6, 144.8, 137.4,
5
148.1, 147.2, 146.7, 145.1, 141.1, 137.4, 135.5, 131.4, 130.9, 65 136.3, 135.6, 134.6, 131.6, 131.2, 130.7, 129.4, 128.1, 127.7,
130.9, 129.3, 129.0, 127.8, 127.4, 127.4, 126.7, 126.2, 125.4,
123.6, 123.1, 121.0, 120.5, 110.5, 110.3, 107.9, 101.0 ppm. IR
10 (KBr): ν 3062, 3026, 2895, 2207, 1476, 1232, 1034, 927, 728,
699 cm-1. ESI HRMS: calcd. for C30H2N2O2+H 441.1603, found
441.1604.
127.3, 127.2, 126.5, 123.9, 123.5, 112.4, 110.4, 107.8, 101.0 ppm.
IR (KBr): ν 3135, 3057, 3025, 1477, 1323, 1237, 1039, 745, 702
cm-1. ESI HRMS: calcd. for C26H18N2O2+H 391.1447, found
391.1449.
70 2-methyl-7,8-diphenylimidazo[1,2-]pyridine (3na). 8 h, 45%
1
4,5-diphenyl-2,3-dihydro-1H-benzo[4,5]imidazo[1,2-]
yield; H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 6.8 Hz, 1H),
1
cyclopenta [e] pyridine (3ha). 12 h, 53% yield; H NMR (400
7.40 (s, 1H), 7.35-7.34 (m, 2H), 7.29-7.19 (m, 6H), 7.13-7.11 (m,
2H), 6.86 (d, J = 7.2 Hz, 1H), 2.45 (s, 3H) ppm; 13C NMR (100
MHz, CDCl3):  144.3, 139.8, 135.4, 135.2, 131.1, 129.8, 127.9,
15 MHz, CDCl3): δ 8.04 (d, J = 8.0 Hz, 1H), 7.96 (d, J = 8.4 Hz,
1H),7.47 (t, J = 7.6 Hz, 1H), 7.33(t, J = 6.8 Hz, 2H), 7.29-7.19 (m,
7H), 7.12-7.10 (m, 2H), 3.73 (t, J = 7.6 Hz, 2H), 2.87 (t, J = 7.6 75 127.9, 127.4, 126.8, 123.6, 114.9, 109.7, 14.7 ppm. IR (KBr): ν
Hz, 2H), 2.41-2.34 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3): 
149.7, 145.2, 139.8, 139.0, 138.2, 135.8, 131.3, 129.6, 129.4,
20 127.8, 127.2, 127.0, 126.1, 124.8, 124.6, 120.5, 120.1, 112.9,
32.2, 30.7, 22.5 ppm. IR (KBr): ν 3057, 3025, 2926, 1500, 1478,
1028, 736, 695 cm-1. ESI HRMS: calcd. for C26H20N2+H
361.1705, found 361.1706.
5,6-diphenyl-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-
25 ]quinoline (3ia). 12 h, 60% yield; 1H NMR (400 MHz, CDCl3):
δ 8.23 (d, J = 8.8 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.46 (t, J =
8.0 Hz, 1H), 7.31-7.15 (m, 9H), 7.07-7.05 (m, 2H), 3.56 (t, J =
6.4 Hz, 2H), 2.44 (t, J = 6.0 Hz, 2H), 2.11-2.05 (m, 2H), 1.84-
1.78 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3):  177.1, 145.5,
30 142.7, 138.1, 136.6, 136.0, 130.9, 130.4, 129.8, 127.8, 127.7,
127.0, 126.9, 124.4, 120.2, 118.5, 115.4, 28.9, 28.0, 22.3, 22.2
ppm. IR (KBr): ν 3055, 3023, 2926, 1494, 1441, 1292, 728, 697
cm-1. ESI HRMS: calcd. for C27H22N2+H 375.1861, found
375.1863.
3025, 2919, 2853, 1319, 1269, 753, 733, 698 cm-1. ESI HRMS:
calcd. for C20H16N2+H 285.1392, found 285.1395.
Notes and references
1
(a) A. T. Balaban, D. C. Oniciu, A. R. Katritzky, Chem. Rev., 2004,
104, 2777; (b) J. A. Joule, K. Mills, Heterocyclic Chemistry, 5th ed.;
Wiley: New York, 2010; For selected recent examples of biological
activity of imidazo[1,2-]pyridines: (c) M. Lhassani, O. Chavignon,
J. M. Chezal, J. C. Teulade, J. P. Chapat, R. Snoeck, G. Andrei, J.
Balzarini, E. De Clercq, A. Gueiffier, Eur. J. Med. Chem., 1999, 34,
271; (d) K. C. Rupert, J. R. Henry, J. H. Dodd, S. A. Wadsworth, D.
E. Cavender, G. C. Olini, B. Fahmy, J. Siekierka, Bioorg. Med.
Chem. Lett., 2003, 13, 347; (e) Y. Rival, G. Grassy, G. Michel,
Chem. Pharm. Bull., 1992, 40, 1170; (f) Y. Abe, H. Kayakiri, S.
Satoh, T. Inoue, Y. Sawada, K. Imai, N. Inamura, M. Asano, C.
Hatori, A. Katayama, T. Oku, H. Tanaka, J. Med. Chem., 1998, 41,
564; For selected recent examples of biological activity of
pyrido[1,2-]benzimidazoles: (g) M. Hammad, A. Mequid, M. E.
Ananni, N. Shafik, Egypt. J. Chem., 1987, 29, 5401; (h) M. Hranjec,
I. Piantanida, M. Kralj, L. Šuman, K. Pavelí, G. Karminski-Zamola,
J. Med. Chem., 2008, 51, 4899; (i) S. K. Kotovskaya, Z. M.
Baskakova, V. N. Charushin, O. N. Chupakhin, E. F. Belanov, N. I.
Bormotov, S. M. Balakhnin, O. A. Serova, Pharm. Chem. J., 2005,
39, 574; (j) H. L. Koo, H. L. Dupont, Curr. Opin. Gastroenterol.
2010, 26, 17.
80
85
90
95
35 7,8-dimethyl-3,4-diphenylbenzo[4,5]imidazo[1,2-]pyridine
(3ja). 7 h, 80% yield; 1H NMR (400 MHz, CDCl3): δ 8.38 (d, J =
7.2 Hz, 1H), 7.73 (s, 1H), 7.66 (s, 1H), 7.42-7.40 (m, 2H), 7.34-
7.17(m, 8H), 6.93 (d, J = 7.2 Hz, 1H), 2.48 (s, 3H), 2.44 （s,
3H） ppm; 13C NMR (100 MHz, CDCl3):  148.3, 143.8, 139.6,
40 139.3, 135.3, 134.7, 131.1, 130.5, 129.7, 128.1, 128.0, 127.5,
127.4, 127.2, 123.3, 120.2, 113.3, 110.1, 20.7, 20.6 ppm. IR
(KBr): ν 3049, 2968, 2917, 1615, 1498, 1433, 753, 701 cm-1. ESI
HRMS: calcd. for C25H20N2+H 349.1705, found 349.1706.
1,3-dimethyl-8,9-diphenyl-1,10a-dihydropyrido[2,1-f]purine-
100 2
(a) A. Berson, V. Descatoire, A. Sutton, D. Fau, B. Maulny, N.
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3
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Vadrot, G. Feldmann, B. Berthon, T. Tordjmann, D. J. Pessayre,
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105
1
45 2,4(3H,4aH)-dione (3ka). 9 h, 67% yield; H NMR (400 MHz,
CDCl3): δ 9.07 (d, J = 6.8 Hz, 1H), 7.36-7.30 (m, 5H), 7.27-7.16
(m, 6H), 3.62 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): 155.1,
152.0, 151.3, 147.5, 141.6, 138.7, 134.0, 131.2, 129.6, 128.2,
128.0, 127.9, 127.8, 127.4, 125.7, 117.0, 30.2, 27.8 ppm. IR
50 (KBr): ν 3057, 2956, 1700, 1660, 1540, 758, 702 cm-1. ESI
HRMS: calcd. for C23H18N4O2+K 421.1067, found421.1067.
110 4
(a) K. Gudmundsson, S. D. Boggs, PCT Int. Appl. WO 2006026703,
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5
For selected recent examples of synthesis of imidazo[1,2-
]pyridines, see: (a) N. Chernyak, V. Gevorgyan, Angew. Chem.,
Int. Ed., 2010, 49, 2743; (b) A. L. Rousseau, P. Matlaba, C. J.
Parkinson, Tetrahedron Lett., 2007, 48, 4079; (c) E. F. DiMauro, J.
M. Kennedy, J. Org. Chem., 2007, 72, 1013; (d) M. Aginagalde, Y.
Vara, A. Arrieta, R. Zangi, V. L. Cebolla, A. Delgado-Camon, F. P.
Cossio, J. Org. Chem., 2010, 75, 2776; (e) M. Adib, A. Mohamadi,
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1
7,8-diphenylimidazo[1,2-]pyridine (3la). 12 h, 81% yield; H
115
NMR (400 MHz, CDCl3): δ 8.16 (d, J = 6.8 Hz, 1H), 7.67-7.65
(m, 2H), 7.37-7.16 (m, 10H), 6.95 (d, J = 6.8, 1H) ppm; 13C
55 NMR (100 MHz, CDCl3):  145.4, 139.4, 135.5, 135.2, 134.3,
130.9, 129.7, 128.3, 128.0, 127.4, 127.0, 124.2, 115.6, 112.4 ppm.
IR (KBr): ν 3093, 3060, 1482, 1436, 1310, 1142, 756, 699 cm-1.
ESI HRMS: calcd. for C19H14N2+H 271.1235, found 271.1235.
120
6
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 7 of 7
Organic & Biomolecular Chemistry
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14 Determination of the activation of π system in the C-H activation
reaction.
Ph
1.0 equiv
Ph
N
N
N
N
N
N
N
(3')
+ N
Ph
+
standard conditions
Ph
5 h
86%
Ph
5a 5b = 1.2/1
Ph
4a
1.0 equiv
4b
1.0 equiv
/
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 7