Palladium-Catalyzed Synthesis of Fluorescent Benzo[4,5]imidazo[1,2-a]pyridines through Annulation Reaction of Benzimidazoles and Alkynyl Bromides with Internal Alkynes

Article abstract of DOI:10.1021/acs.joc.0c02126

An efficient synthesis of fused azapolycycles based on (benz)imidazole and pyridine scaffolds has been developed. In all cases, the first nucleophilic addition of (benz)imidazoles to alkynyl bromides in tert-pentyl alcohol can proceed in a stereoselective manner to provide (Z)-N-(1-bromo-1-alken-2-yl)benzimidazoles at 110 °C. Sequentially, these adducts containing alkenyl bromide can undergo Pd-catalyzed intermolecular C-H annulation in the presence of internal alkynes in dimethylacetamide, affording fluorescent (benz)imidazole-fused pyridines in good to high yields. These compounds generally exhibit blue or green fluorescences (454-503 nm for solution states and 472-506 nm for solid states), and the fluorescence quantum yields remained in 0.19-0.89 and 0.02-0.74 for solution and solid states, respectively.

Full text of DOI:10.1021/acs.joc.0c02126

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Article
Palladium-Catalyzed Synthesis of Fluorescent
Benzo[4,5]imidazo[1,2-a]pyridines through Annulation Reaction of
Benzimidazoles and Alkynyl Bromides with Internal Alkynes
Xin Chen,§ Peng Sun,§ Baichuan Mo, Chunxia Chen,* and Jinsong Peng*
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ABSTRACT: An efficient synthesis of fused azapolycycles based on (benz)imidazole and pyridine scaffolds has been developed. In
all cases, the first nucleophilic addition of (benz)imidazoles to alkynyl bromides in tert-pentyl alcohol can proceed in a stereoselective
manner to provide (Z)-N-(1-bromo-1-alken-2-yl)benzimidazoles at 110 °C. Sequentially, these adducts containing alkenyl bromide
can undergo Pd-catalyzed intermolecular C−H annulation in the presence of internal alkynes in dimethylacetamide, affording
fluorescent (benz)imidazole-fused pyridines in good to high yields. These compounds generally exhibit blue or green fluorescences
(454−503 nm for solution states and 472−506 nm for solid states), and the fluorescence quantum yields remained in 0.19−0.89 and
0.02−0.74 for solution and solid states, respectively.
reactions for the synthesis of multisubstituted π-expanded
novel benzimidazoles are still highly desired.
INTRODUCTION
■
Substituted (hetero)polycyclic aromatic hydrocarbons have
been playing important roles in the discovery of electronic and
optical materials1 that are desirable for organic photovoltaic
devices,2 field effect transistors,3 redox flow batteries,4 and
light-emitting diodes.5 In particular, aryl-fused (benz)-
imidazoles as electron-transporting and emission functional
units have recently received significant attention in the design,
synthesis, and applications of organic materials.6 These π-
extended benzimidazoles feature increasingly complex designs,
and substituents influence electron mobility, energy levels,
band gaps, solution conformation, and crystal packing. Highly
substituted novel aryl-annulated (benz)imidazoles will further
offer new insights into photophysical processes and in turn
enhance device performance. Therefore, much effort has been
focused on the synthetic methods of (benz)imidazole
derivatives.7a
Recent studies reveal that haloacetylenes can undergo
addition by certain nucleophiles to give halosubstituted olefins
as valuable intermediates for various synthetic processes.16
This chemistry opened up new opportunities for metal-
catalyzed C−H functionalization, and some elegant work has
been done to construct diverse heterocyclic architectures by
Wang,17 Urabe,18 Wu and Jiang,19 and our group20 in recent
years. In parallel with our continuous efforts on the synthesis of
imidazole-based fluorophores through Pd-catalyzed C−H
coupling reactions,20a,b,21 herein we envisioned that (benz)-
imidazoles, alkynyl bromides, and internal alkynes should be
suitable substrates for sequential nucleophilic addition
followed by Pd-catalyzed C−H annulation (Scheme 1).
RESULTS AND DISCUSSION
■
Over the past decades, direct C−H annulation has emerged
as an attractive and powerful tool to construct an π-extended
imidazole-fused architecture.7 The most common approaches
include transition metal-catalyzed cross-coupling reactions
between (benz)imidazoles and internal alkynes. For instances,
For the initial experiments, benzimidazole (1a), bromoethy-
nylbenzene (2a), and diphenylacetylene (4a) as model
Received: September 3, 2020
Miura,8 Dong,9 Hua,10 Li,11 Choudhury,12 Fan,13 Wang,14 and
15
́
Saa reported Rh or Pd-catalyzed various oxidative C−H
annulations of imidazoles and alkynes to build π-extended aryl-
fused imidazole scaffolds, respectively. Despite major advance-
ments in this field, metal-catalyzed alkyne benzannulation
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Scheme 1. Reaction Design for the Construction of π-Extended Polyheterocycles
Scheme 2. Fundamental Data for Nucleophilic Addition
substrates were selected for sequential nucleophilic addition/
Pd-catalyzed intermolecular C−H annulation reaction to
construct π-extended (benz)imidazole 5aaa (Scheme 2 and
Table 1). Our recent study reveals that alkynyl bromides can
undergo addition by the nitrogen nucleophilic reagent
(quinolin-4-ones) to give (Z)-alkenyl bromides regio- and
stereoselectively with good yields in the presence of a base
using tert-pentyl alcohol as the solvent at 110 °C.22 On the
basis of this reaction condition, some new investigations are
summarized in Scheme 2 using benzimidazole (1a) as the
nucleophilic reagent. Using K2CO3 as the base, protonic
solvents (methanol and n-butanol) provided better yields than
nonprotonic solvents such as dimethylformamide (DMF),20a
dimethylacetamide (DMA), dimethyl sulfoxide (DMSO),
toluene, tetrahydrofuran (THF), dichloromethane, DCE, and
acetonitrile (left column, Scheme 2). The effect of other bases
such as K2CO3, K3PO4,22 NaOAc, NaOtBu, KHCO3, Et3N,
Na2CO3, and KOtBu on the reaction is shown in the second
column of Scheme 2, and Cs2CO3 gave a better result,
providing 3a in 78% yield. A set of experiments were carried
out to reveal the role of the reaction temperature and time
(right column, Scheme 2); 110 °C for 24 h was found to be
suitable for this nucleophilic addition.
Based on the above results, the palladium-catalyzed
intermolecular aromatic C−H annulation process of 3a with
diphenylacetylene was then examined. Some fundamental data
are summarized in Table 1, including the catalyst, ligand, and
other reaction conditions such as the solvent, base, temper-
ature, and reaction time. The tert-pentyl alcohol provided the
adduct 3aa in a good yield (78%, Scheme 2); however, it is not
suitable for the Pd-catalyzed C−H annulation as the solvent,
and no desired product was obtained (entry 27, Table 1). We
then examined the model reaction in DMF using Cs2CO3 as
the base, an initial screen of various palladium catalysts (5 mol
%) with Xphos (10 mol %) as the ligand, and we found that
the use of PdCl2(CH3CN)2 gave the best result in 48% yield
(entries 1−6, Table 1). With PdCl2(CH3CN)2 as the catalyst,
the effect of monophosphorus ligands (PCy3, PPh3, JohnPhos,
MePhos, DavePhos, Cy-JohnPhos, tBu-XPhos, and tBu-
MePhos) or bidented phosphorus ligands (DPPB and
DPPE) on the reaction was investigated (entries 7−16,
Table 1). DPPB provided a similar result to PCy3 and
sterically hindered biaryl phosphines (XPhos, JohnPhos,
MePhos, and DavePhos) in yields about 45%, entries 5, 7,
9−11, and 15. DPPE gave a better result, and the yield was
improved to 53% (entry 16). The effect of other bases such as
K2CO3, K3PO4, NaOAc, NaOtBu, KHCO3, Et3N, Na2CO3,
KOtBu, and NaOH on the reaction was next examined (entries
17−25); K2CO3 provided a better result with 75% isolated
yield (entry 17). A survey of reaction media showed that DMA
provided a better yield (83%, entry 28) than those obtained in
DMF, DMSO, tert-pentyl alcohol, toluene, 1,4-dioxane, DCE,
and THF (entries 26−27, and 29−32). Finally, a set of
experiments were carried out to reveal the role of the reaction
temperature (from 80 to 120 °C, entry 33) and time (from 6
to 24 h, entry 34). In general, with increased reaction
temperature and time, higher yields were obtained (from 65 to
83%, entries 28, 33, and 34, Table 1).
Having established the feasibility of this nucleophilic
addition/Pd-catalyzed C−H annulation sequence, we then
explored the scope and generality of (benz)imidazoles and
alkynyl bromides with diphenylacetylene as the partner (Table
2). Under palladium-free reaction conditions, a variety of
(benz)imidazoles 1 reacted smoothly with alkynyl bromides 2
to generate the corresponding addition products 3 in good to
high yields (50−84%, 3aa−3ha and 3ab−3ak, Table 2) with
specific regio- and stereoselectivity. The electronic nature of
benzimidazole affected the outcome to some extent;
benzimidazoles without a substituted group and with
electron-donating substituents at the 5 and 6 positions afforded
higher yields than benzimidazole with an electron-withdrawing
group (entries 1−3 and 6−8, Table 2). Asymmetrically
substituted benzimidazole was used to investigate the
regioselectivity of the N-atoms in the nucleophilic addition
step. In the case of 4-methyl-substituted benzimidazole 1d
(entry 4, Table 2), the reaction occurred mainly at the
sterically accessible N-atom to give 3da as the major
regioisomer.20a The structure of 3da and 3da′ was elucidated
by 2D 1H-NOESY spectra of the corresponding pure annulated
products 5daa and 5daa′ (Supporting Information). For 5-
substituted benzimidazoles 1f−1h, all the cases provided the
two regioisomers in a ratio of ca. 1:1 (entries 6−8, Table 2). 2-
Methylimidazole 1e was transformed into the corresponding
products 3ea in a modest yield (57%) probably because of the
B
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a
Table 1. Annulation Reaction Condition Optimization
b
entry
catalyst/ligand
Pd(OAc)2/XPhos
base/solvent
yield
1
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
Cs2CO3/DMF
K2CO3/DMF
K3PO4/DMF
NaOAc/DMF
NaOtBu/DMF
KHCO3/DMF
Et3N/DMF
Na2CO3/DMF
KOtBu/DMF
NaOH/DMF
K2CO3/DMSO
K2CO3/tert-pentyl alcohol
K2CO3/DMA
K2CO3/toluene
K2CO3/1,4-dioxane
K2CO3/DCE
42
38
40
28
48
35
47
38
48
45
40
35
35
37
45
53
75
66
68
70
63
58
70
68
0
2
3
4
5
6
7
8
9
Pd2(dba)3/XPhos
PdCl2/XPhos
PdCl2(PPh3)2/XPhos
PdCl2(CH3CN)2/XPhos
Pd(PPh3)4/XPhos
PdCl2(CH3CN)2/PCy3
PdCl2(CH3CN)2/PPh3
PdCl2(CH3CN)2/JohnPhos
PdCl2(CH3CN)2/MePhos
PdCl2(CH3CN)2/DavePhos
PdCl2(CH3CN)2/Cy-JohnPhos
PdCl2(CH3CN)2/tBu-XPhos
PdCl2(CH3CN)2/tBu-MePhos
PdCl2(CH3CN)2/DPPB
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
PdCl2(CH3CN)2/DPPE
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
58
0
83
63
53
54
32
K2CO3/THF
K2CO3/DMA
K2CO3/DMA
c
d
e
65 /67 /73
f
g
h
65 /73 /75
a
Reaction conditions: 3aa (0.2 mmol), 4a (0.24 mmol), base (0.24 mmol), catalyst (0.01 mmol), ligand (0.02 mmol), and solvent (1.5 mL), 120
b
c
d
e
f
g
h
°C, 24 h. Isolated yields. 80 °C. 100 °C. 110 °C. 6 h. 12 h. 18 h.
steric repulsion between the methyl substituent at the 2
position and alkynyl bromide (entry 5, Table 2). Using
benzimidazole 1a as the substrate, the scope of bromoacety-
lenes 2 was then investigated in the nucleophilic addition step
(entries 6−15, Table 2). Diverse substituted bromoacetylenes
such as aryl (entries 6−12), heteroaryl (entry 15), and alkyl
(entries 13 and 14) substituents gave the corresponding
adducts 3ab−3ak in good yields. For aryl-substituted alkynyl
bromides 2, this reaction condition was compatible with
various functionalities including methyl, methoxy, fluorine, and
chlorine on the aromatic ring (entries 6−12, Table 2). In
general, the reactivity of aryl bromoacetylenes 2 with an
electron-donating group at the para-, meta-, or ortho-positions
(entries 6−9 and 11) was more than that with an electron-
withdrawing group (entries 10 and 12). The reactive activity of
bromoacetylenes 2 can be further improved by the
replacement of the aryl group with alkyl substituents (n-
C4H9 and n-C6H13), affording the adducts 3ai and 3aj in 84
and 83% yield, respectively (entries 13 and 14, Table 2).
With prepared adducts (Z)-N-(1-bromo-1-alken-2-yl)-
benzimidazoles 3 in the hands, the scope and generality of
the second step were then examined (the right column of
Table 2, and Scheme 3). First, with diphenylacetylene 4a as the
coupling partner, 3aa−3ha and 3ab−3ak can be smoothly
transformed into the corresponding annulation products 5 in
moderate to good yields (38−86%, Table 2) through Pd-
catalyzed direct C−H bond functionalization. The electronic
nature of benzimidazole motifs of adducts 3 seemed to affect
the efficiency of this C−H annulation heavily. When electron-
withdrawing substituents (such as dichloro, 3ca, and 5-chloro,
3ha) were introduced, the corresponding products 5caa and
5haa were obtained in lower yields (38 and 45% respectively,
entries 3 and 8, Table 2). The electronic nature of R2 groups
did not seem to hamper the C−H annulation process; both
(hetero)aryl and alkyl substituents gave high yields (71−86%,
C
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Table 2. Addition Reaction of (Benz)imidazoles to Bromoalkynes and Sequential Intermolecular Cyclization with 1,2-
a
Diphenylethyne
b
b
entry
R1
R2
3, yield (%)
5, yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
13
14
15
16
H
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
p-Me-C6H4
p-MeO-C6H4
m-Me-C6H4
m-MeO-C6H4
m-Cl-C6H4
o-Me-C6H4
o-F-C6H4
3aa, 78
3ba, 75
3ca, 50
5aaa, 83
5baa, 78
5caa, 38
5daa, 75
5eaa, 46
5faa, 79
5gaa, 78
5haa, 45
5aba, 81
5aca, 81
5ada, 81
5aea, 83
5afa, 71
5aga, 75
5aha, 73
5aia, 86
5aja, 85
5aka, 72
5,6-dimethyl
5,6-dichloro
4-methyl
c
3da, 55
d
3ea, 57
e
5-methyl
5-methoxy
5-chloro
3fa, 74
e
3ga, 73
e
3ha, 68
H
H
H
H
H
H
H
H
H
H
3ab, 78
3ac, 77
3ad, 75
3ae, 77
3af, 65
3ag, 72
3ah, 65
3ai, 84
3aj, 83
3ak, 63
n-C4H9
n-C6H13
thiophen-2-yl
a
Reaction conditions: step 1: 1 (0.5 mmol), 2 (0.75 mmol), Cs2CO3 (0.75 mmol), tert-pentyl alcohol (2 mL), 120 °C, 24 h; step 2: 3aa (0.2
b
mmol), 4a (0.24 mmol), PdCl2(MeCN)2 (0.01 mmol), DPPE (0.02 mmol), K2CO3 (0.24 mmol), DMA (1.5 mL), 120 °C, 24 h. Isolated yields.
c
d
The mixture of 4-methyl and 7-methyl regioisomers was obtained, and the ratio (4.5:1) of two isomers was determined by NMR analysis. 2-
e
methyl imidazole 1e was used. The mixture of 5-substituted and 6-substituted regioisomers was obtained in the ratio of 1:1 as determined by
NMR analysis.
entries 9−16, Table 2). Second, the scope and limitation of
alkyne substrates 4 were next examined using 3aa as the other
substrate (Scheme 3). The effect of electron-rich and electron-
deficient aryl-substituted symmetrical alkynes was first
investigated (4b−4i and 4l, Scheme 3). A variety of
substituents (Me, OMe, F, Cl, Br, and CF3) on the internal
arylalkynes was applicable, providing the corresponding
products 5aab−5aai in 72−85% yields. Both electron-donating
(4b−c) and electron-withdrawing (4d−h) substituents can be
incorporated at the para- or metaposition (5aab−5aah,
Scheme 3). The introduction of electron-withdrawing
substituents (F, Cl, Br, and CF3) into the phenyl ring afforded
higher yields than electron-donating substituents (Me and
OMe). However, on extending the substrate scope to fused
aryl alkyne (α-naphthyl, 4l), the reaction cannot proceed to
give the corresponding product 5aal. In addition, hetero
alkynes (4i) can also be transformed into the corresponding
product 5aai in 72% yield. Because of the lack of conjugation,
the symmetrically substituted alkyl alkyne 4j is less reactive.23
The desired dialkyl-substituted product 5aaj was obtained in
48% yield. When ethyl phenylpropiolate 4k was used, the ethyl
1,3-diphenylbenzo[4,5]imidazo[1,2-a]pyridine-4-carboxylate
5aak was exclusively formed as a single regioisomer in 79%
yield. In addition, the Pd-catalyzed C−H annulation of 3aa and
internal arylalkyne (4f) can be carried out on a 1.0 mmol scale
to give 5aaf without compromising the yield (81 vs 75%,
Scheme 3). It is worth noting that C−Br or C−Cl compatible
with the reaction condition are particularly appealing, offering
great opportunity for further synthetic manipulations. For
instance, the reaction of 5aaf with phenyl boronic acid or
ethynylbenzene led to the formation of double arylated or
alkynated products 6 or 7 through the Suzuki or Sonogashira
cross-coupling in 83 and 45% yield, respectively (Scheme 4b).
Performing the nucleophilic addition and Pd-catalyzed C−H
annulation in one-pot manner potentially makes this synthetic
method more versatile and practical. Therefore, one-pot
approach was finally explored. As shown in Scheme 4a, the
reaction of benzimidazoles (1a−b), ethynyl bromides (2a and
2i), and diphenylacetylene 4a can smoothly proceed to
generate the corresponding products (5aaa, 5baa, and 5aia)
in 52, 58, and 47% yield, respectively.
Based on the above results and our previous
work20a,c,21b,22,24 and others,25 a plausible reaction pathway
for the synthesis of benzo[4,5]imidazo[1,2-a]pyridines was
outlined in Scheme 5. In the nucleophilic addition step,
benzimidazole 1 might form a hydrogen bond with the solvent
(tert-pentyl alcohol) to give hydrogen-bond structure 1′. After
the deprotonation of N−H by the base (Cs2CO3), 1
underwent the nucleophilic addition to 1-bromo-1-alkyne 2
in a specifically regio- and stereoselective manner to provide-
(Z)-N-alkenylated bromide 3 (step 1, Scheme 5). Using
PdCl2(CH3CN)2 as a precatalyst for the annulation reaction,
the formation of palladium black was observed after the
reaction was quenched by water, implying that the aromatic
C−H functionalization was promoted by the Pd0−PdII−Pd0
catalytic cycle.25 Taking this fact into account, a possible C−H
alkenylation catalytic cycle was outlined in the second step
(Scheme 5). After the reduction of PdCl2(CH3CN)2 to the
actual catalyst Pd(0), oxidative addition of the vinyl bromide 3
to Pd(0) is performed to produce a vinylpalladium 8. The
coordination and subsequent syn migratory insertion of the
internal alkyne to 8 would afford a new vinylic palladium
D
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a b
,
Scheme 3. Pd-Catalyzed Annulation of 3aa and Various Internal Alkynes
a
Reaction conditions: 3aa (0.2 mmol), 4 (0.24 mmol), PdCl2(MeCN)2 (0.01 mmol), DPPE (0.02 mmol), K2CO3 (0.24 mmol), DMA (1.5 mL),
b
c
120 °C, 24 h. Isolated yields. 1 mmol scale.
intermediate 10. The final product 5 can be formed possibly
through two distinct pathways (a C−H activation or
electrophilic palladation pathway)26 from an alkenyl-Pd(II)
species 10. Both a concerted metalation deprotonation
transition state 1127 and an electrophilic palladation−
deprotonation28 of the arene can form the same seven-
membered palladacycle 12, which underwent C−C bond-
forming reductive elimination to afford the desired benzo-
[4,5]imidazo[1,2-a]pyridine 5 and regenerated a Pd(0) species
for the next catalytic cycle.
The absorption and fluorescence spectra of π-extended
(benz)imidazole-fused aromatic polycycles 5 are shown in
Table 3 and Figure 1 for solution states and in Table 4 and
Figure 2 for solid states, respectively. These benzo[4,5]-
imidazo[1,2-a]pyridines generally exhibit blue or green
fluorescence, with a λmax of emission between 454 and 503
nm in CH2Cl2 (Table 3) and 472−506 nm in the solid state
(Table 4). The excitation curves feature two to three well-
defined peaks, which all produce the same emission peak
(Figure 1 and Table 3). The cause appears to be most likely
the result of nonradiative relaxation to the lowest electronic
excited state (S1) from a higher electronic level and radiative
relaxation to the ground state (S0).29 Functional group
modifications on the fused skeleton can affect the emissive
properties; electron-donating groups at the benzimidazole
moiety lead to a bathochromic shift of emission (entries 1−4,
Table 3). In addition, by the increasing the number of
conjugated aromatic rings and planarity, emission maxima of
(benz)imidazo[1,2-a]pyridines were bathochromically shifted
(entries 1−5, Table 3 and Figure 1A). For R2 substituents at
the C-1 position of the backbone (Figure 1B), the heteroaryl
group (thiophen-2-yl, compound 5aka) had the opposite
effect, and the emission band was significantly hypsochromi-
cally shifted compared with the compound 5aaa. A similar
result was also observed when adding two thiophen-2-yl or
alkyl groups at C-3 and C-4 (compounds 5aai and 5aaj, Figure
1C) compared with 5aaa. A change of less than 30 nm for λmax
was observed among these compounds, which emitted with
E
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Scheme 4. One-Pot Synthesis and Derivatives of Benzimidazole-fused Pyridines
3). ΦF of compounds 5−7 remained in the range of 0.02−0.74
in the solid state (Table 4).
Scheme 5. Proposed Reaction Pathway
CONCLUSIONS
■
In conclusion, we have developed an efficient protocol for the
modular synthesis of (benz)imidazole-fused pyridine deriva-
tives. The process is based on stereoselective nucleophilic
addition of (benz)imidazoles to alkynyl bromides and
subsequent palladium-catalyzed intermolecular C−H annula-
tion with readily accessible internal alkynes. This synthetic
method exhibits a broad substrate scope with good to high
yields and excellent stereo- and regioselectivity. Because of the
interesting and important optical properties of π-extended
(benz)imidazoles, these fluorophores are good emitter
candidates for OLEDs, OFETs, and photovoltaic cells.
Therefore, the result presented here should be of considerable
interest for the discovery of fluorescent materials.
EXPERIMENTAL SECTION
■
General Information. Chemicals were all purchased from
commercial supplies and used without further purification unless
otherwise stated. Solvents were dried and purified according to the
standard procedures before use. Reactions were monitored by
analytical thin-layer chromatography. All reactions were conducted
in a dried glassware. Purification of reaction products was done by
flash chromatography with 230−400 mesh silica gel. Benzimidazoles
(1c31a and 1d31b), alkynyl bromides (2a−2k22), and internal alkynes
(4a−4j32) were prepared according to the literature methods. All
these substrates are known compounds, and the spectroscopic and
physical data are matched with those from the literature. Melting
points were determined on a melting point apparatus in open
capillaries and were uncorrected. 1H NMR spectra were recorded on a
500 MHz spectrometer, and 13C NMR spectra were recorded at 126
MHz. Unless otherwise stated, deuterochloroform (CDCl3) was used
as a solvent. Chemical shifts (δ) are given in parts per million
downfield relative to tetramethylsilane. Chemical shifts for carbon
resonances are reported in parts per million and are referenced to the
carbon resonance of the solvent CHCl3 (δ = 77.16 ppm). Coupling
constants are given in hertz. High-resolution mass spectra were
recorded on a BIO TOF Q mass spectrometer equipped with an
electrospray ion source (ESI), operated in the positive mode.
significantly improved Stokes shifts in the range of 0.49−0.73
μm−1 (entries 1−24, Table 3). The lowest wavelength peak
exhibited an unusually high excitation−emission differential of
1.87 μm−1.30 In these conjugated systems, the fluorescence
quantum yield (ΦF) remained in the range of 0.19−0.89 in
CH2Cl2, and the introduction of the alkyl and methoxyl group
into the (benz)imidazole-fused pyridine core showed a good
fluorescence quantum yield (entries 2, 8, 15, 16, and 23, Table
F
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mL) was added to the mixture via a syringe at room temperature. The
vial was sealed and put into a preheated oil bath at 120 °C for 24 h.
The mixture was cooled to room temperature, quenched with water
(5 mL), and diluted with dichloromethane (5 mL). The layers were
separated, and the aqueous layer was extracted with 3 × 5 mL of
dichloromethane. The combined organic extracts were dried over
anhydrous magnesium sulfate, filtered, and concentrated in vacuo.
The crude product was then purified by flash chromatography on
silica gel (H), eluting with the mixture of ethyl acetate and petroleum
ether (from 1:5 to 1:3).
Table 3. Photophysical Properties of π-Extended Aza-
Polycycles 5 in Solution
a
b
λmax (nm)
ε
)
λem
(nm)
excitation−emission
c
entry compd
(M−1cm−1
ΦF
differentials (μm−1
)
1
5aaa
5baa
5caa
5daa
5eaa
5aba
5aca
5ada
5aea
5afa
5aha
5aia
259 [47538]
370 [8733]
264 [53083]
377 [10866]
265 [65100]
375 [10700]
268 [57633]
375 [9836]
256 [59633]
374 [7988 ]
263 [45733]
369 [8533]
264 [47860]
381 [9733]
265 [45680]
365 [8736]
265 [56280]
366 [9866]
266 [43733]
365 [7763]
265 [56280]
366 [9866]
274 [6835]
368 [56280]
258 [33500]
369 [6659]
266 [57100]
367 [9766]
265 [36133]
372 [8533]
281 [52500]
374 [13966]
264 [45083]
374 [7599]
265 [46866]
373 [7963]
266 [50500]
376 [8399]
256 [42866]
375 [7883]
264 [44933]
374 [8133]
256 [7090]
308 [13966]
375 [47866]
250 [44233]
351 [7366]
256 [46966]
334 [8533]
374 [9033]
481
488
476
503
473
480
476
497
481
480
481
494
482
454
480
474
485
476
483
483
488
460
0.72
0.51
0.89
0.79
0.53
0.37
0.68
0.47
0.75
0.53
0.76
0.55
0.78
0.51
0.78
0.62
0.74
0.48
0.41
0.27
0.74
0.48
0.65
0.34
0.68
0.37
0.75
0.47
0.83
0.69
0.87
0.79
0.34
0.23
0.41
0.28
0.65
0.47
0.68
0.59
0.38
0.20
0.85
0.68
0.53
0.81
0.74
0.65
0.38
0.19
1.78
0.62
1.74
0.60
1.67
0.57
1.74
0.68
1.79
0.56
1.72
0.63
1.69
0.52
1.76
0.73
1.69
0.65
1.68
0.66
1.69
0.65
1.63
0.69
1.80
0.64
1.56
0.52
1.69
0.60
1.45
0.56
1.73
0.61
1.67
0.58
1.69
0.59
1.84
0.60
1.74
0.62
1.73
1.07
0.49
1.87
0.72
1.84
0.93
0.61
2
3
(Z)-1-(2-Bromo-1-phenylvinyl)-1H-benzo[d]imidazole (3aa).33
White solid, mp 123−125 °C; yield, 78% (116.2 mg, eluent:
1
4
EtOAc/petroleum ether = 1/4); H NMR (400 MHz, CDCl3): δ
8.07 (s, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.39 (t, J = 7.3 Hz, 1H), 7.33−
7.28 (m, 3H), 7.20 (t, J = 7.6 Hz, 1H), 7.17−7.14 (m, 2H), 7.03 (s,
1H), 6.98 (d, J = 8.0 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3): δ
143.4, 143.0, 139.5, 134.8, 132.9, 130.1, 129.2, 126.1, 123.7, 122.9,
120.6, 111.5, 104.6.
5
6
(Z)-1-(2-Bromo-1-phenylvinyl)-5,6-dimethyl-1H-benzo[d]-
7
imidazole (3ba).34 White solid, mp 153−155 °C; yield, 75% (122.2
1
mg, eluent: EtOAc/petroleum ether = 1/5); H NMR (400 MHz,
8
CDCl3): δ 7.96 (s, 1H), 7.67 (s, 1H), 7.41 (t, J = 7.3 Hz, 1H), 7.36−
7.32 (m, 2H), 7.20−7.18 (m, 2H), 7.04 (s, 1H), 6.81 (s, 1H), 2.39 (s,
3H), 2.29 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3): δ 142.3,
142.0, 139.6, 134.9, 133.0, 131.8, 131.5, 130.0, 129.2, 126.0, 120.6,
111.6, 104.7, 20.6, 20.3.
(Z)-1-(2-Bromo-1-phenylvinyl)-5,6-dichloro-1H-benzo[d]-
imidazole (3ca). White solid, mp 174−176 °C; yield, 50% (91.5 mg,
eluent: EtOAc/petroleum ether = 1/5); 1H NMR (500 MHz,
CDCl3): δ 7.97 (s, 1H), 7.87 (s, 1H), 7.34 (t, J = 7.4 Hz, 1H), 7.29−
7.24 (m, 2H), 7.07−7.04 (m, 3H), 7.00 (s, 1H). 13C{1H} NMR (126
MHz, CDCl3): δ 143.7, 141.6, 137.8, 133.0, 129.4, 128.4, 127.0,
126.2, 124.8, 120.8, 111.7, 104.7. HRMS (ESI) m/z: [M + H]+ calcd
for C15H10BrCl2N2, 366.9399; found, 366.9400, 368.9373.
Mixture of (Z)-1-(2-Bromo-1-phenylvinyl)-4-methyl-1H-benzo-
[d]imidazole (3da) and (Z)-1-(2-Bromo-1-phenylvinyl)-7-methyl-
1H-benzo[d]imidazole (3da′). White solid, mp 145−147 °C; yield,
55% (85.8 mg, eluent: EtOAc/petroleum ether = 1/4); the ratio
(3da:3da′ = 4.5:1) is determined by 1H NMR; 1H NMR (400 MHz,
CDCl3): δ 8.06 (s, 1H3da), 8.03 (s, 0.17H3da′), 7.43−7.30 (m,
4.62Hoverlap), 7.22−7.15 (m, 2.44Hoverlap), 7.12−7.09 (m, 2.49Hoverlap),
7.02 (s, 1H3da), 6.95 (d, J = 8.0 Hz, 0.23H3da′), 6.86−6.79 (m, 1H3da),
2.75 (s, 3H3da), 2.69 (s, 0.67H3da′). 13C{1H} NMR (151 MHz,
CDCl3): δ 141.5, 141.1, 140.6, 138.5, 133.7, 131.5, 131.2, 129.9,
129.5, 129.4, 129.1, 129.0, 128.1, 127.9, 127.8, 127.7, 127.6, 127.5,
125.0, 122.9, 122.6, 122.4, 122.2, 108.0, 107.6, 103.6, 15.6, 15.5.
HRMS (ESI) m/z: [M + H]+ calcd for C16H14BrN2, 313.0335; found,
313.0333, 315.0309.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
5aja
5aka
5aab
5aac
5aad
5aae
5aaf
5aag
5aah
5aai
(Z)-1-(2-Bromo-1-phenylvinyl)-2-methyl-1H-imidazole (3ea).
White solid, mp 173−174 °C; yield, 57% (74.6 mg, eluent: EtOAc/
1
petroleum ether = 1/5); H NMR (400 MHz, CDCl3): δ 7.41−7.35
(m, 3H), 7.17−7.09 (m, 3H), 7.07 (s, 1H), 6.89 (s, 1H), 2.25 (s, 3H).
13C{1H} NMR (151 MHz, CDCl3): δ 143.9, 139.9, 133.9, 128.8,
128.2, 127.3, 124.3, 118.4, 105.4, 12.2. HRMS (ESI) m/z: [M + H]+
calcd for C12H12BrN2, 263.0178; found, 263.0179, 265.0154.
Mixture of (Z)-1-(2-Bromo-1-phenylvinyl)-6-methyl-1H-benzo-
[d]imidazole (3fa) and (Z)-1-(2-Bromo-1-phenylvinyl)-5-methyl-
1H-benzo[d]imidazole (3fa′). Yellow oil; yield, 74% (115.9 mg,
eluent: EtOAc/petroleum ether = 1/5); the ratio (3fa:3fa′ = 1:1) is
23
24
5aaj
469
485
5aak
1
1
determined by H NMR; H NMR (500 MHz, CDCl3): δ 7.90 (s,
1H), 7.85 (s, 1H), 7.64 (d, J = 8.3 Hz, 1H), 7.55 (s, 1H), 7.28−7.22
(m, 2H), 7.21−7.14 (m, 4H), 7.06−6.99 (m, 5H), 6.94−6.86 (m,
3H), 6.74 (d, J = 8.3 Hz, 1H), 6.68 (s, 1H), 2.34 (s, 3H), 2.25 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 142.6, 141.9, 141.4, 140.3,
138.4, 138.3, 133.74, 133.71, 132.7, 132.1, 131.5, 129.9, 128.9, 128.1,
128.0, 125.0, 124.9, 124.1, 123.4, 119.2, 118.9, 110.2, 110.0, 103.9,
103.88, 103.34, 103.31, 20.7, 20.5. HRMS (ESI) m/z: [M + H]+ calcd
for C16H14BrN2, 313.0335; found, 313.0335.
a
b
Concentration: 1.0 × 10−5 M in CH2Cl2. Maxima of major well-
c
defined bands. Determined by p-terphenyl (ΦF = 0.87, excited at 265
nm) as a standard.
General Procedures for the Synthesis of (Z)-N-(1-Bromo-1-
alken-2-yl) (benz)imidazoles 3. A 10 mL vial equipped with a
magnetic stirring bar was charged with (benz)imidazoles 1 (0.5 mmol,
1.0 equiv), alkynyl bromides 2 (0.75 mmol, 1.5 equiv), and Cs2CO3
(244.5 mg, 0.75 mmol, 1.5 equiv), and then, tert-pentyl alcohol (2.0
Mixture of (Z)-1-(2-Bromo-1-phenylvinyl)-5-methoxy-1H-benzo-
[d]imidazole (3ga) and (Z)-1-(2-Bromo-1-phenylvinyl)-6-methoxy-
1H-benzo[d]imidazole (3ga′). Yellow oil; yield, 73% (120.2 mg,
G
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Figure 1. Absorption and Emission Spectra of Representative Benzo[4,5]imidazo[1,2-a]pyridines in CH2Cl2.
1
1
eluent: EtOAc/petroleum ether = 1/5); the ratio (3ga:3ga′ = 1:1) is
determined by H NMR; H NMR (500 MHz, CDCl3): δ 7.97 (s,
1H), 7.93 (s, 1H), 7.75 (d, J = 1.8 Hz, 1H), 7.67 (d, J = 8.6 Hz, 1H),
7.31−7.27 (m, 2H), 7.22 (td, J = 7.6, 3.3 Hz, 4H), 7.16 (dd, J = 8.6,
1.9 Hz, 1H), 7.08−7.02 (m, 5H), 6.97 (s, 1H), 6.94 (s, 1H), 6.91 (d, J
= 1.9 Hz, 1H), 6.79 (d, J = 8.6 Hz, 1H). 13C{1H} NMR (126 MHz,
CDCl3): δ 143.1, 142.6, 140.9, 138.0, 137.9, 133.4, 133.3, 132.4,
130.5, 129.8, 129.23, 129.19, 128.5, 128.3, 128.2, 127.8, 127.5, 124.9,
124.8, 123.2, 122.6, 120.3, 119.3, 111.2, 110.4, 104.5, 104.0. HRMS
(ESI) m/z: [M + H]+ calcd for C15H11BrClN2, 332.9789; found,
332.9792.
1
1
determined by H NMR; H NMR (500 MHz, CDCl3): δ 7.94 (s,
1H), 7.85 (s, 1H), 7.65 (d, J = 8.8 Hz, 1H), 7.31−7.27 (m, 2H),
7.25−7.20 (m, 6H), 7.08−7.05 (m, 5H), 6.94 (d, J = 1.1 Hz, 1H),
6.90 (d, J = 1.4 Hz, 1H), 6.84 (dt, J = 8.8, 1.9 Hz, 1H), 6.77−6.74 (m,
2H), 6.36 (d, J = 2.3 Hz, 1H), 3.75 (s, 3H), 3.60 (s, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 156.1, 155.5, 143.2, 142.2, 141.0, 140.9,
138.4, 138.3, 136.7, 133.8, 133.7, 132.6, 129.9, 129.0, 128.1, 127.8,
126.4, 125.0, 119.9, 112.7, 111.0, 110.9, 103.7, 103.2, 101.5, 94.0,
54.7, 54.6. HRMS (ESI) m/z: [M + H]+ calcd for C16H14BrN2O,
329.0284; found, 329.0289.
(Z)-1-(2-Bromo-1-(p-tolyl)vinyl)-1H-benzo[d]imidazole (3ab).33
White solid, mp 94−96 °C; yield, 78% (121.7 mg, eluent: EtOAc/
petroleum ether = 1/5); H NMR (400 MHz, CDCl3): δ 7.99 (s,
1H), 7.80 (d, J = 8.1 Hz, 1H), 7.23 (t, J = 7.1 Hz, 1H), 7.13 (t, J = 7.3
Hz, 1H), 7.05 (d, J = 8.1 Hz, 2H), 6.98 (d, J = 8.3 Hz, 2H), 6.91 (d, J
Mixture of (Z)-1-(2-Bromo-1-phenylvinyl)-5-chloro-1H-benzo[d]-
imidazole (3ha) and (Z)-1-(2-Bromo-1-phenylvinyl)-6-chloro-1H-
benzo[d]imidazole (3ha′). Yellow oil; yield, 68% (113.4 mg, eluent:
EtOAc/petroleum ether = 1/4); the ratio (3ha:3ha′ = 1:1) is
1
H
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(s, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.31−7.26 (m, 1H), 7.25−7.21 (m,
1H), 7.18−7.12 (m, 2H), 7.07−7.02 (m, 1H), 7.00−6.94 (m, 2H),
6.83 (td, J = 7.8, 1.7 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3): δ
142.3, 141.7, 137.2, 135.5, 134.3, 131.6, 129.4, 129.1, 125.0, 123.2,
122.9, 122.0, 119.7, 110.3, 105.3. HRMS (ESI) m/z: [M + H]+ calcd
for C15H11BrClN2, 332.9789; found, 332.9782, 334.9761.
Table 4. Photophysical Properties of Aza-Polycycles 5 in the
Solid State
a
entry
compd
Solid
a
b
λem (nm) (λex nm)
ΦF
1
2
3
4
5
6
7
8
5aaa
5caa
5daa
5eaa
5faa, 5ffa′
5gaa, 5gaa′
5haa, 5haa′
5aba
5aca
5ada
5afa
5aga
5aia
5aja
5aab
5aac
5aae
5aaf
5aah
5aai
5aaj
5aak
6
7
487/(379)
490/(382)
483/(382)
493/(381)
496/(381)
512/(379)
488/(380)
488/(379)
486/(379)
486/(379)
491/(381)
480/(379)
472/(383)
531/(385)
485/(379)
485/(381)
481/(381)
495/(382)
494/(382)
487/(380)
501/(356)
493/(381)
506/(382)
479/(381)
0.58
0.30
0.56
0.12
0.41
0.16
0.31
0.36
0.60
0.45
0.39
0.26
0.34
0.24
0.39
0.05
0.04
0.49
0.74
0.02
0.44
0.12
0.16
0.74
(Z)-1-(2-Bromo-1-(2-methoxyphenyl)vinyl)-1H-benzo[d]-
imidazole (3ag). White solid, mp 102−104 °C; yield, 72% (118.1
1
mg, eluent: EtOAc/petroleum ether = 1/4); H NMR (400 MHz,
CDCl3): δ 8.08 (s, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.34 (t, J = 7.7 Hz,
1H), 7.26 (t, J = 7.6 Hz, 1H), 7.18 (t, J = 7.6 Hz, 1H), 7.12 (s, 1H),
7.07 (d, J = 7.4 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 6.91 (t, J = 7.5 Hz,
1H), 6.86 (d, J = 8.3 Hz, 1H), 3.61 (s, 3H). 13C{1H} NMR (151
MHz, CDCl3): δ 157.2, 143.5, 143.2, 136.7, 133.2, 131.3, 129.7,
123.7, 123.4, 122.5, 120.9, 120.3, 111.5, 111.3, 107.8, 55.6. HRMS
(ESI) m/z: [M + H]+ calcd for C16H14BrN2O, 329.0284; found,
329.0285, 331.0265.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
(Z)-1-(2-Bromo-1-(2-fluorophenyl)vinyl)-1H-benzo[d]imidazole
(3ah). White solid, mp 125−127 °C; yield, 65% (102.7 mg, eluent:
EtOAc/petroleum ether = 1/3); 1H NMR (400 MHz, CDCl3): δ 7.98
(s, 1H), 7.81 (d, J = 8.1 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.25 (t, J =
7.2 Hz, 1H), 7.21−7.14 (m, 3H), 7.01 (s, 1H), 6.92 (d, J = 7.9 Hz,
2H). 13C{1H} NMR (151 MHz, CDCl3): δ 158.8 (159.6, 157.9, d,
4
1JC−F = 254 Hz), 142.2, 141.8, 132.7 (132.68, 132.66, d, JC−F = 3
3
Hz), 131.8, 130.5 (130.5, 130.45, d, JC‑F = 9 Hz), 128.0 (128.04.
4
3
128.02, d, JC−F = 3 Hz), 123.8 (123.83, 123.8, d, JC−F = 5 Hz),
3
122.7, 121.8, 121.5 (121.57, 121.5, d, JC−F = 10 Hz), 119.6, 115.7
(115.8, 115.6, d, 2JC−F = 22 Hz), 110.0, 109.0 (109.0, 108.9, d, 2JC−F
=
15 Hz). 19F NMR (376 MHz, CDCl3): δ −113.7. HRMS (ESI) m/z:
[M + H]+ calcd for C15H11BrFN2, 317.0084; found, 317.0087,
319.0064.
(Z)-1-(1-Bromohex-1-en-2-yl)-1H-benzo[d]imidazole (3ai). Yel-
low oil; yield, 84% (116.8 mg, eluent: EtOAc/petroleum ether = 1/
4); 1H NMR (400 MHz, CDCl3): δ 7.90 (s, 1H), 7.88−7.79 (m, 1H),
7.33−7.31 (m, 3H), 6.51 (s, 1H), 2.58 (t, J = 6.7 Hz, 2H), 1.31−1.27
(m, 4H), 0.83 (t, J = 6.8 Hz, 3H). 13C{1H} NMR (151 MHz,
CDCl3): δ 142.3, 140.8, 139.2, 131.4, 122.5, 121.6, 119.5, 109.9,
103.1, 34.8, 27.8, 20.9, 12.6. HRMS (ESI) m/z: [M + H]+ calcd for
C13H16BrN2, 279.0491; found, 279.0490, 281.0467.
a
Emission maximum in the solid state with the corresponding
b
wavelength of excitation in parentheses. Absolute fluorescence
quantum yields were measured in the solid film on a quartz slide
with an integrating sphere (excited at 265 nm).
= 8.0 Hz, 1H), 6.89 (s, 1H), 2.26 (s, 3H). 13C{1H} NMR (151 MHz,
CDCl3): δ 142.3, 142.0, 139.4, 138.4, 131.9, 131.0, 128.8, 125.0,
122.6, 121.7, 119.5, 110.5, 102.4, 20.3.
(Z)-1-(1-Bromooct-1-en-2-yl)-1H-benzo[d]imidazole (3aj).35 Yel-
low oil; yield, 83% (127.1 mg, eluent: EtOAc/petroleum ether = 1/
5); 1H NMR (400 MHz, CDCl3): δ 7.77 (s, 1H), 7.70 (br, 1H), 7.13
(br, 3H), 6.31 (s, 1H), 2.35 (br, 2H), 1.11−0.94 (m, 8H), 0.65 (t, J =
6.4 Hz, 3H).
(Z)-1-(2-Bromo-1-(4-methoxyphenyl)vinyl)-1H-benzo[d]-
imidazole (3ac).33 White solid, mp 140−142 °C; yield, 77% (126.2
mg, eluent: EtOAc/petroleum ether = 1/5); H NMR (400 MHz,
CDCl3): δ 8.00 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.26 (t, J = 7.7 Hz,
1H), 7.18 (t, J = 7.6 Hz, 1H), 7.10 (t, J = 7.6 Hz, 1H), 7.04 (s, 1H),
6.97 (dd, J = 17.5, 7.7 Hz, 2H), 6.83 (t, J = 7.5 Hz, 1H), 6.78 (d, J =
8.3 Hz, 1H), 3.53 (s, 3H). HRMS (ESI) m/z: [M + H]+ calcd for
C16H14BrN2O, 329.0284; found, 329.0290, 331.0263.
(Z)-1-(2-Bromo-1-(m-tolyl)vinyl)-1H-benzo[d]imidazole (3ad).
White solid, mp 89−91 °C; yield, 75% (117.0 mg, eluent: EtOAc/
petroleum ether = 1/4); H NMR (400 MHz, CDCl3): δ 7.96 (s,
1H), 7.79 (d, J = 8.1 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.15−7.09 (m,
3H), 6.93−6.91 (m, 3H), 6.86 (t, J = 4.4 Hz, 1H), 2.19 (s, 3H).
13C{1H} NMR (151 MHz, CDCl3): δ 142.3, 142.0, 138.5, 138.0,
133.8, 131.9, 129.9, 128.0, 125.6, 122.6, 122.3, 121.7, 119.4, 110.5,
103.4, 20.3. HRMS (ESI) m/z: [M + H]+ calcd for C16H14BrN2,
313.0335; found, 313.0338, 315.0319.
(Z)-1-(2-Bromo-1-(3-methoxyphenyl)vinyl)-1H-benzo[d]-
imidazole (3ae). White solid, mp 142−144 °C; yield, 77% (126.2 mg,
eluent: EtOAc/petroleum ether = 1/5); 1H NMR (400 MHz,
CDCl3): δ 7.96 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.19 (t, J = 7.5 Hz,
1H), 7.13−7.08 (m, 2H), 6.95−6.88 (m, 2H), 6.83−6.80 (m, 1H),
6.62−6.60 (m, 2H), 3.60 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3):
δ 159.0, 142.2, 141.9, 138.2, 135.1, 131.8, 129.2, 122.6, 121.8, 119.4,
117.4, 114.2, 110.8, 110.5, 103.9, 54.3. HRMS (ESI) m/z: [M + H]+
calcd for C16H14BrN2O, 329.0284; found, 329.0290, 331.0265.
(Z)-1-(2-Bromo-1-(3-chlorophenyl)vinyl)-1H-benzo[d]imidazole
(3af). White solid, mp 112−114 °C; yield, 65% (112.8 mg, eluent:
EtOAc/petroleum ether = 1/3); 1H NMR (400 MHz, CDCl3): δ 8.00
1
(Z)-1-(2-Bromo-1-(thiophen-2-yl)vinyl)-1H-benzo[d]imidazole
(3ak). Brown solid, mp 102−104 °C; yield, 63% (97.6 mg, eluent:
EtOAc/petroleum ether = 1/4); 1H NMR (400 MHz, CDCl3): δ 8.05
(s, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.36−7.32 (m, 2H), 7.27 (t, J = 7.6
Hz, 1H), 7.15 (d, J = 8.0 Hz, 1H), 7.05 (s, 1H), 6.97−6.92 (m, 1H),
6.75 (d, J = 3.6 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3): δ 143.2,
142.6, 138.2, 134.0, 132.8, 128.1, 127.5, 126.7, 123.8, 123.0, 120.6,
111.3, 103.9. HRMS (ESI) m/z: [M + H]+ calcd for C13H10BrN2S,
304.9743; found, 304.9744, 306.9727.
General Procedures for the Synthesis of Benzo[4,5]-
imidazo[1,2-a] Pyridines. A 10 mL Schlenk tube equipped with a
magnetic stirring bar was charged with alkenyl bromides 3 (0.2 mmol,
1.0 equiv), internal alkynes 4 (0.24 mmol, 1.2 equiv), and K2CO3
(33.1 mg, 0.24 mmol, 1.2 equiv), and then, PdCl2(MeCN)2 (0.01
mmol, 2.6 mg) and dppe (0.02 mmol, 8 mg) were added. Finally,
DMA (1.5 mL) was added to the mixture via a syringe at room
temperature under air. The tube was sealed and put into a preheated
oil bath at 130 °C for 24 h. The mixture was cooled to room
temperature, quenched with water (5 mL), and diluted with ethyl
acetate (6 mL). The layers were separated, and the aqueous layer was
extracted with 3 × 5 mL of ethyl acetate. The combined organic
extracts were dried over anhydrous sodium sulfate, filtered, and
concentrated in vacuo. The crude product was then purified by flash
chromatography on silica gel (H), eluting with 10−20% ethyl acetate/
petroleum ether.
1
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Figure 2. Absorption and Emission Spectra of Representative Benzo[4,5]imidazo[1,2-a]pyridines in the solid state.
J
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Article
1,3,4-Triphenylbenzo[4,5]imidazo[1,2-a]pyridine (5aaa).36 Yel-
low-green solid, mp 274−276 °C; yield, 83% (65.7 mg, eluent:
EtOAc/petroleum ether = 1/6); 1H NMR (400 MHz, CDCl3): δ 7.86
(d, J = 8.2 Hz, 1H), 7.59−7.52 (m, 5H), 7.41−7.39 (m, 2H), 7.33−
7.20 (m, 4H), 7.15 (br, 5H), 6.89 (t, J = 7.3 Hz, 1H), 6.78 (s, 1H),
6.57 (d, J = 8.5 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 148.8,
144.6, 139.0, 138.6, 138.4, 134.5, 133.5, 130.3, 129.0, 128.7, 128.5,
128.2, 128.1, 127.2, 127.1, 126.7, 126.3, 126.0, 123.8, 119.3, 119.2,
114.4, 113.5.
7,8-Dimethyl-1,3,4-triphenylbenzo[4,5]imidazo[1,2-a]pyridine
(5baa). Yellow-green solid, mp 249−251 °C; yield, 78% (66.1mg,
eluent: EtOAc/petroleum ether = 1/7); 1H NMR (400 MHz,
CDCl3): δ 7.69 (s, 1H), 7.65−7.59 (m, 5H), 7.46 (d, J = 7.0 Hz, 2H),
7.35−7.28 (m, 3H), 7.21 (br, 5H), 6.80 (s, 1H), 6.37 (s, 1H), 2.34 (s,
3H), 2.14 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3): δ 149.4,
144.5, 139.6, 139.3, 139.2, 135.7, 134.7, 134.2, 131.4, 129.9, 129.8,
129.5, 129.2, 129.0, 128.1, 128.0, 127.9, 127.6, 127.3, 126.8, 120.0,
114.9, 114.5, 20.8, 20.6. HRMS (ESI) m/z: [M + H]+ calcd for
C31H25N2, 425.2012; found, 425.2012.
7,8-Dichloro-1,3,4-triphenylbenzo[4,5]imidazo[1,2-a]pyridine
(5caa). Yellow-green solid, mp 253−255 °C; yield, 38% (35.3 mg,
eluent: EtOAc/petroleum ether = 1/7); 1H NMR (400 MHz,
CDCl3): δ 8.00 (s, 1H), 7.70−7.62 (m, 5H), 7.44 (d, J = 7.4 Hz, 2H),
7.37−7.31 (m, 3H), 7.23 (br, 5H), 6.90 (s, 1H), 6.68 (s, 1H).
13C{1H} NMR (151 MHz, CDCl3): δ 151.3, 144.9, 141.1, 139.5,
138.9, 135.0, 133.5, 131.2, 130.6, 129.7, 129.5, 129.2, 129.0, 128.5,
128.3, 128.2, 128.0, 127.7, 127.1, 123.9, 120.9, 116.1, 115.7. HRMS
(ESI) m/z: [M + H]+ calcd for C29H19Cl2N2, 465.0920; found,
465.0919.
6-Methyl-1,3,4-triphenylbenzo[4,5]imidazo[1,2-a]pyridine
(5daa). Yellow-green solid, mp 276−278 °C; 49%, (40.2 mg, eluent:
EtOAc/petroleum ether = 1/6); 1H NMR (600 MHz, CDCl3): δ 7.65
(dt, J = 18.9, 7.4 Hz, 5H), 7.59 (d, J = 6.8 Hz, 2H), 7.36 (dt, J = 12.6,
6.9 Hz, 3H), 7.28 (d, J = 5.5 Hz, 5H), 7.23 (d, J = 7.1 Hz, 1H), 6.93−
6.90 (m, 1H), 6.86 (s, 1H), 6.53 (s, 1H), 2.75 (s, 3H). 13C{1H} NMR
(151 MHz, CDCl3): δ 149.17, 145.21, 139.71, 139.53, 139.40, 135.56,
134.60, 131.88, 130.05, 129.92, 129.84, 129.20, 129.10, 129.04,
128.11, 127.81, 127.47, 127.30, 126.94, 124.86, 120.22, 115.36,
111.97, 17.16. HRMS (ESI) m/z: [M + H]+ calcd for C30H23N2,
411.1856; found, 411.1856.
9-Methyl-1,3,4-triphenylbenzo[4,5]imidazo[1,2-a]pyridine
(5daa′). Yellow-green solid, mp 272−274 °C; yield, 28% (23.1 mg,
eluent: EtOAc/petroleum ether = 1/8); 1H NMR (400 MHz, CDCl3)
δ 7.80 (d, J = 8.1 Hz, 1H), 7.64−7.57 (m, 2H), 7.51−7.42 (m, 5H),
7.35−7.32 (m, 4H), 7.23 (br, 5H), 6.90 (d, J = 7.2 Hz, 1H), 6.87 (s,
1H), 1.64 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3): δ 151.3,
146.7, 140.7, 139.9, 139.2, 138.3, 135.5, 131.4, 129.9, 129.6, 129.4,
129.3, 128.2, 128.1, 127.7, 127.4, 127.1, 127.0, 125.4, 125.2, 124.3,
117.8, 117.1, 21.4. HRMS (ESI): [M + H]+ m/z calcd for C30H23N2,
411.1856; found, 411.1856.
125.7, 125.6, 121.1, 118.7, 114.2, 113.3, 112.9, 20.9, 20.7. HRMS
(ESI) m/z: [M + H]+ calcd for C30H23N2, 411.1856; found, 411.1856.
Mixture of 7-Methoxy-1,3,4-triphenylbenzo[4,5]imidazo[1,2-a]-
pyridine (5gaa) and 8-Methoxy-1,3,4-triphenylbenzo[4,5]imidazo-
[1,2-a]pyridine (5gaa′). Yellow-green solid, mp 234−236 °C; yield,
78% (66.5 mg, eluent: EtOAc/petroleum ether = 1/6); the ratio
(5gaa:5gaa′ = 1:3) is determined by 1H NMR; 1H NMR (500 MHz,
CDCl3): δ 7.74 (d, J = 9.0 Hz, 1H), 7.60−7.54 (m, 6.6H), 7.39 (d, J =
7.0 Hz, 2.64H), 7.30−7.20 (m, 4.58H), 7.14 (br, 6H), 6.96 (dd, J =
9.0, 2.5 Hz, 1H), 6.77 (s, 0.33H), 6.75 (s, 1H), 6.53 (dd, J = 9.2, 2.5
Hz, 0.32H), 6.43 (d, J = 9.2 Hz, 0.32H), 5.97 (d, J = 2.4 Hz, 1H),
3.75 (s, 1H), 3.40 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ
156.8, 153.2, 148.3, 139.2, 138.4, 138.3, 138.1, 138.0, 137.8, 134.5,
133.4, 130.3, 130.2, 129.0, 128.9, 128.7, 128.5, 128.49, 128.1, 128.08,
127.9, 127.14, 127.12, 126.6, 126.58, 126.3, 126.2, 126.1, 125.4, 122.9,
119.7, 114.3, 114.2, 114.1, 114.0, 110.3, 99.8, 96.2, 54.5, 54.2. HRMS
(ESI) m/z: [M + H]+ calcd for C30H22N2O, 427.1805; found,
427.1806.
Mixture of 7-Chloro-1,3,4-triphenylbenzo[4,5]imidazo[1,2-a]-
pyridine (5haa) and 8-Chloro-1,3,4-triphenylbenzo[4,5]imidazo-
[1,2-a]pyridine (5haa′). Yellow-green solid, mp 201−203 °C; yield,
45% (38.8 mg, eluent: EtOAc/petroleum ether = 1/6); the ratio
(5haa:5haa′ = 1:1) is determined by 1H NMR; 1H NMR (500 MHz,
CDCl3): δ 7.82 (d, J = 1.7 Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.58−
7.53 (m, 9H), 7.37 (d, J = 7.7 Hz, 4H), 7.29−7.22 (m, 8H), 7.15 (br,
10H), 6.84 (dd, J = 9.0, 1.9 Hz, 1H), 6.80 (d, J = 2.5 Hz, 2H), 6.51
(d, J = 1.6 Hz, 1H), 6.45 (d, J = 9.0 Hz, 1H). 13C{1H} NMR (126
MHz, CDCl3): δ 149.7, 149.4, 145.4, 143.0, 139.7, 139.4, 138.43,
138.42, 138.0, 134.14, 134.1, 133.0, 132.8, 130.2, 130.19, 129.6, 129.4,
129.2, 128.7, 128.6, 128.3, 128.2, 128.0, 127.9, 127.2, 127.1, 127.0,
126.8, 126.5, 126.1, 125.9, 124.63, 124.61, 119.9, 119.8, 118.6, 114.8,
114.2, 113.4. HRMS (ESI) m/z: [M + H]+ calcd for C29H20ClN2,
431.1310; found, 431.1314.
3,4-Diphenyl-1-(p-tolyl)benzo[4,5]imidazo[1,2-a]pyridine
(5aba). Yellow-green solid, mp 253−255 °C; yield, 81% (66.4 mg,
eluent: EtOAc/petroleum ether = 1/6); 1H NMR (400 MHz,
CDCl3): δ 7.94 (d, J = 8.2 Hz, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.49−
7.46 (m, 2H), 7.43−7.40 (m, 2H), 7.38−7.30 (m, 4H), 7.23 (br, 5H),
6.99 (t, J = 7.8 Hz, 1H), 6.83 (s, 1H), 6.74 (d, J = 8.5 Hz, 1H), 2.55
(s, 3H). 13C{1H} NMR (151 MHz, CDCl3): δ 148.9, 144.6, 139.1,
139.0, 138.8, 138.4, 134.5, 130.6, 130.3, 128.7, 128.5, 128.0, 127.1,
127.0, 126.6, 126.3, 125.7, 123.8, 119.2, 119.1, 114.4, 113.6, 20.6.
HRMS (ESI) m/z: [M + H]+ calcd for C30H23N2, 411.1856; found,
411.1856.
1-(4-Methoxyphenyl)-3,4-diphenylbenzo[4,5]imidazo[1,2-a]-
pyridine (5aca).37 Yellow-green solid, mp 238−240 °C; yield, 81%
1
(69.0 mg, eluent: EtOAc/petroleum ether = 1/7); H NMR (400
MHz, CDCl3): δ 7.94 (d, J = 8.2 Hz, 1H), 7.57 (d, J = 8.7 Hz, 2H),
7.47 (d, J = 6.7 Hz, 2H), 7.40−7.30 (m, 4H), 7.23 (br, 5H), 7.13 (d, J
= 8.7 Hz, 2H), 7.00 (t, J = 7.8 Hz, 1H), 6.83 (s, 1H), 6.76 (d, J = 8.5
Hz, 1H), 3.96 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3): δ 159.8,
148.9, 144.6, 139.0, 138.5, 138.4, 134.5, 130.3, 129.5, 128.7, 128.6,
127.1, 127.0, 126.6, 126.3, 125.8, 125.7, 123.8, 119.3, 119.2, 114.5,
113.6, 113.4, 54.5.
3,4-Diphenyl-1-(m-tolyl)benzo[4,5]imidazo[1,2-a]pyridine
(5ada). Yellow-green solid, mp 236−238 °C; yield, 81% (66.4 mg,
eluent: EtOAc/petroleum ether = 1/8); 1H NMR (400 MHz,
CDCl3): δ 7.94 (d, J = 8.2 Hz, 1H), 7.55−7.53 (m, 2H), 7.49−7.46
(m, 2H), 7.43−7.40 (m, 2H), 7.39−7.30 (m, 4H), 7.23 (br, 5H), 6.99
(t, J = 8.4 Hz, 1H), 6.83 (s, 1H), 6.76−6.71 (m, 1H), 2.55 (s, 3H).
13C{1H} NMR (151 MHz, CDCl3): δ 148.9, 144.6, 139.1, 139.0,
3-Methyl-5,7,8-triphenylimidazo[1,5-a]pyridine (5eaa). Yellow-
green solid, mp 232−235 °C; yield, 46% (33.1 mg, eluent: EtOAc/
1
petroleum ether = 1/6); H NMR (400 MHz, CDCl3): δ 7.52−7.50
(m, 6H), 7.35−7.31 (m, 5H), 7.18−7.16 (m, 5H), 6.60 (s, 1H), 2.09
(s, 3H). 13C{1H} NMR (151 MHz, CDCl3): δ 139.1, 137.2, 136.5,
135.1, 134.5, 133.6, 130.2, 130.0, 129.8, 129.3, 128.9, 128.5, 128.4,
128.1, 128.0, 127.7, 126.8, 120.6, 118.4, 17.7. HRMS (ESI) m/z: [M
+ H]+ calcd for C26H21N2, 361.1699; found, 361.1697.
Mixture of 7-Methyl-1,3,4-triphenylbenzo[4,5]imidazo[1,2-a]-
pyridine (5faa) and 8-Methyl-1,3,4-triphenylbenzo[4,5]imidazo-
[1,2-a]pyridine (5faa′). Yellow-green solid, mp 207−209 °C; yield,
79% (64.8 mg, eluent: EtOAc/petroleum ether = 1/6); the ratio
138.8, 138.4, 134.5, 130.6, 130.3, 128.7, 128.5, 128.0, 127.1, 127.0,
126.6, 126.3, 125.8, 123.8, 119.2, 119.1, 114.4, 113.6, 20.6. HRMS
(ESI) m/z: [M + H]+ calcd for C30H23N2, 411.1856; found, 411.1857.
1-(3-Methoxyphenyl)-3,4-diphenylbenzo[4,5]imidazo[1,2-a]-
pyridine (5aea). Yellow-green solid, mp 227−229 °C; yield, 83%
1
1
(5faa:5faa′ = 1:1) is determined by H NMR; H NMR (500 MHz,
CDCl3): δ 7.74 (d, J = 8.4 Hz, 1H), 7.64 (s, 1H), 7.59−7.51 (m,
10H), 7.39 (d, J = 8.0 Hz, 4H), 7.28−7.20 (m, 6H), 7.14 (br, 11H),
6.79−6.69 (m, 3H), 6.45 (d, J = 8.5 Hz, 1H), 6.31 (s, 1H), 2.37 (s,
3H), 2.18 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 148.8,
148.5, 142.71, 142.69, 138.8, 138.41, 138.38, 134.5, 134.48, 133.8,
133.5, 133.47, 130.3, 130.28, 129.1, 129.0, 128.9, 128.7, 128.5, 128.1,
128.08, 128.03, 128.0, 127.1, 127.0, 126.6, 126.5, 126.3, 126.26, 125.9,
1
(70.7 mg, eluent: EtOAc/petroleum ether = 1/6); H NMR (400
MHz, CDCl3): δ 7.85 (d, J = 8.2 Hz, 1H), 7.47−7.36 (m, 3H), 7.31−
7.21 (m, 4H), 7.16−7.13 (br, 6H), 7.10−7.08 (m, 2H), 6.91 (t, J =
7.5 Hz, 1H), 6.78 (s, 1H), 6.65 (d, J = 8.5 Hz, 1H), 3.77 (s, 3H).
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13C{1H} NMR (151 MHz, CDCl3): δ 159.0, 148.8, 144.6, 138.9,
138.4, 138.3, 134.5, 134.4, 130.3, 129.2, 128.7, 128.4, 127.1, 127.0,
126.6, 126.3, 125.9, 123.8, 120.3, 119.4, 119.2, 114.9, 114.2, 113.6,
113.2, 54.5.
NMR (151 MHz, CDCl3): δ 149.1, 144.6, 138.6, 138.2, 136.2, 136.1,
135.5, 133.5, 131.6, 130.1, 128.9, 128.6, 128.5, 128.1, 128.0, 127.9,
127.8, 125.7, 123.7, 119.2, 119.1, 114.5, 113.4, 20.4, 20.2. HRMS
(ESI) m/z: [M + H]+ calcd for C31H25N2, 425.2012; found, 425.2011.
3,4-Bis(4-methoxyphenyl)-1-phenylbenzo[4,5]imidazo[1,2-a]-
pyridine (5aac). Yellow-green solid, mp 236−238 °C; yield, 75%
1-(3-Chlorophenyl)-3,4-diphenylbenzo[4,5]imidazo[1,2-a]-
pyridine (5afa). Yellow-green solid, mp 236−238 °C; yield, 71%
1
1
(68.4 mg, eluent: EtOAc/petroleum ether = 1/5); H NMR (400
(61.0 mg, eluent: EtOAc/petroleum ether = 1/6); H NMR (400
MHz, CDCl3): δ 7.92 (d, J = 8.2 Hz, 1H), 7.69−7.57 (m, 5H), 7.42
(d, J = 8.7 Hz, 2H), 7.36 (t, J = 7.7 Hz, 1H), 7.17 (d, J = 8.7 Hz, 2H),
6.97−6.89 (m, 3H), 6.81 (s, 1H), 6.78 (d, J = 8.7 Hz, 2H), 6.62 (d, J
= 8.4 Hz, 1H), 3.83 (s, 3H), 3.78 (s, 3H). 13C{1H} NMR (151 MHz,
CDCl3): δ 157.9, 157.8, 149.2, 144.6, 138.3, 138.1, 133.6, 131.5,
130.7, 129.9, 128.9, 128.5, 128.2, 128.1, 126.9, 125.1, 125.0, 123.7,
119.1, 114.5, 113.4, 112.8, 112.6, 54.2, 54.1. HRMS (ESI) m/z: [M +
H]+ calcd for C31H25N2O2, 457.1911; found, 457.1910.
MHz, CDCl3): δ 7.96 (d, J = 8.2 Hz, 1H), 7.68 (s, 1H), 7.66−7.61
(m, 1H), 7.57−7.56 (m, 2H), 7.48−7.46 (m, 2H), 7.43−7.31 (m,
4H), 7.23 (br, 5H), 7.04 (t, J = 7.8 Hz, 1H), 6.85 (s, 1H), 6.73 (d, J =
8.5 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3): δ 149.8, 145.7,
139.9, 139.2, 137.9, 136.1, 135.3, 135.2, 131.3, 130.4, 130.3, 129.7,
129.3, 128.2, 128.1, 127.8, 127.6, 127.5, 127.4, 125.1, 120.7, 120.5,
115.7, 114.3. HRMS (ESI) m/z: [M + H]+ calcd for C29H20ClN2,
431.1310; found, 431.1310.
3,4-Bis(4-fluorophenyl)-1-phenylbenzo[4,5]imidazo[1,2-a]-
1-(2-Methoxyphenyl)-3,4-diphenylbenzo[4,5]imidazo[1,2-a]-
pyridine (5aga).38 Yellow-green solid, mp 275−278 °C; yield, 75%
pyridine (5aad). Yellow-green solid, mp 282−284 °C; yield, 83%
1
1
(71.7 mg, eluent: EtOAc/petroleum ether = 1/6); H NMR (400
(63.9 mg, eluent: EtOAc/petroleum ether = 1/5); H NMR (400
MHz, CDCl3): δ 7.96 (d, J = 8.2 Hz, 1H), 7.67 (br, 5H), 7.47−7.35
(m, 5H), 7.27 (d, J = 8.3 Hz, 2H), 7.19 (d, J = 8.5 Hz, 2H), 7.02 (t, J
= 7.6 Hz, 1H), 6.82 (s, 1H), 6.67 (d, J = 8.5 Hz, 1H). 13C{1H} NMR
(151 MHz, CDCl3): δ 162.4 (163.2, 161.5, d, 1JC−F = 257 Hz), 162.2
MHz, CDCl3): δ 7.97 (d, J = 8.2 Hz, 1H), 7.68−7.64 (m, 1H), 7.58−
7.50 (m, 3H), 7.43−7.32 (m, 4H), 7.29−7.21 (m, 6H), 7.15 (d, J =
8.3 Hz, 1H), 7.01 (t, J = 7.8 Hz, 1H), 6.90 (s, 1H), 6.73 (d, J = 8.4
Hz, 1H), 3.68 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3): δ 158.0,
149.7, 145.5, 139.9, 139.5, 137.2, 135.8, 131.8, 131.4, 131.2, 130.0,
129.9, 128.2, 128.0, 127.6, 127.3, 126.7, 124.7, 123.6, 121.2, 120.5,
120.0, 115.6, 113.7, 111.0, 55.6.
1
(163.0, 161.3, d, JC−F = 257 Hz), 149.7, 145.6, 139.9, 139.1, 135.1
4
3
(135.2, 135.1, d, JC−F = 3.4 Hz), 134.3, 133.1 (133.1, 133.0, d, JC−F
= 8 Hz), 131.4 (131.5, 131.4, d, 3JC−F = 8 Hz), 131.2 (131.3, 131.2, d,
4JC−F = 3.4 Hz), 130.2, 129.5, 129.2 (129.2, 129.1, d, 2JC−F = 13 Hz),
1-(2-Fluorophenyl)-3,4-diphenylbenzo[4,5]imidazo[1,2-a]-
pyridine (5aha).37 Yellow-green solid, mp 235−237 °C; yield, 73%
2
125.9, 125.1, 120.6, 120.3, 115.5, 115.4, 115.3 (115.3, 115.2, d, JC−F
1
= 15 Hz), 115.1, 114.6. HRMS (ESI) m/z: [M + H]+ calcd for
C29H19F2N2, 433.1511; found, 433.1510.
(60.5 mg, eluent: EtOAc/petroleum ether = 1/6); H NMR (400
MHz, CDCl3): δ 7.96 (d, J = 8.3 Hz, 1H), 7.71−7.60 (m, 2H), 7.57
(d, J = 4.8 Hz, 1H), 7.48 (t, J = 6.6 Hz, 2H), 7.45−7.31 (m, 5H), 7.24
(br, 5H), 7.03 (t, J = 7.7 Hz, 1H), 6.92−7.85 (m, 1H), 6.72 (t, J = 8.4
Hz, 1H). 19F NMR (376 MHz, CDCl3): δ −112.5. HRMS (ESI) m/z:
[M + H]+ calcd for C29H20FN2, 415.1605; found, 415.1605.
1-Butyl-3,4-diphenylbenzo[4,5]imidazo[1,2-a]pyridine (5aia).
Yellow-green solid, mp 187−189 °C; yield, 86% (64.7 mg, eluent:
EtOAc/petroleum ether = 1/5); 1H NMR (400 MHz, CDCl3): δ 8.11
(d, J = 8.5 Hz, 1H), 8.03 (d, J = 8.2 Hz, 1H), 7.53 (t, J = 7.6 Hz, 1H),
7.45−7.43 (m, 2H), 7.38−7.22 (m, 9H), 6.80 (s, 1H), 3.49−3.38 (m,
2H), 2.04−1.96 (m, 2H), 1.73−1.64 (m, 2H), 1.10 (t, J = 7.3 Hz,
3H). 13C{1H} NMR (151 MHz, CDCl3): δ 150.2, 145.8, 141.5, 140.1,
139.7, 135.7, 131.4, 129.8, 129.6, 128.1, 128.0, 127.5, 127.3, 125.7,
124.8, 120.8, 120.5, 114.8, 112.9, 33.3, 29.2, 22.5, 14.0. HRMS (ESI)
m/z: [M + H]+ calcd for C27H25N2, 377.2012; found, 377.2012.
1-Hexyl-3,4-diphenylbenzo[4,5]imidazo[1,2-a]pyridine (5aja).
Yellow-green solid, mp 184−186 °C; yield, 85% (68.7 mg, eluent:
EtOAc/petroleum ether = 1/6); 1H NMR (400 MHz, CDCl3): δ 8.06
(d, J = 8.5 Hz, 1H), 7.98 (d, J = 8.2 Hz, 1H), 7.48 (t, J = 7.6 Hz, 1H),
7.40−7.38 (m, 2H), 7.35−7.30 (m, 2H), 7.28−7.26 (m, 1H), 7.26−
7.21 (m, 4H), 7.20−7.17 (m, 2H), 6.76 (s, 1H), 3.44−3.35 (m, 2H),
2.00−1.93 (m, 2H), 1.66−1.58 (m, 2H), 1.45−1.36 (m, 4H), 0.93 (t,
J = 7.0 Hz, 3H). 13C{1H} NMR (151 MHz, CDCl3): δ 150.2, 145.8,
141.5, 140.1, 139.7, 135.7, 131.4, 129.8, 129.6, 128.1, 128.0, 127.5,
127.3, 125.7, 124.8, 120.8, 120.5, 114.7, 112.8, 33.6, 31.7, 29.1, 27.1,
22.6, 14.1. HRMS (ESI) m/z: [M + H]+ calcd for C29H29N2,
405.2325; found, 405.2325.
3,4-Diphenyl-1-(thiophen-2-yl)benzo[4,5]imidazo[1,2-a]pyridine
(5aka).37 Dark green solid, mp 252−255 °C; yield, 72% (57.9 mg,
eluent: EtOAc/petroleum ether = 1/6); 1H NMR (400 MHz,
CDCl3): δ 7.95 (d, J = 8.2 Hz, 1H), 7.66 (d, J = 5.1 Hz, 1H), 7.50−
7.38 (m, 4H), 7.38−7.28 (m, 4H), 7.23 (br, 5H), 7.10−7.04 (m, 1H),
7.03 (s, 1H), 6.73 (d, J = 8.5 Hz, 1H). 13C{1H} NMR (151 MHz,
CDCl3): δ 149.8, 145.6, 139.5, 139.1, 135.3, 134.3, 132.1, 131.3,
129.8, 129.6, 129.5, 128.3, 128.2, 128.1, 127.8, 127.7, 127.5, 125.0,
120.8, 120.4, 117.8, 114.2.
1-Phenyl-3,4-di-p-tolylbenzo[4,5]imidazo[1,2-a]pyridine (5aab).
Yellow-green solid, mp 246−248 °C; yield, 76% (64.7mg, eluent:
EtOAc/petroleum ether = 1/6); 1H NMR (400 MHz, CDCl3): δ 7.93
(d, J = 8.2 Hz, 1H), 7.65−7.59 (m, 5H), 7.38−7.34 (m, 3H), 7.18−
7.13 (m, 4H), 7.05 (d, J = 8.0 Hz, 2H), 6.95 (t, J = 8.1 Hz, 1H), 6.83
(s, 1H), 6.63 (d, J = 8.5 Hz, 1H), 2.37 (s, 3H), 2.32 (s, 3H). 13C{1H}
3,4-Bis(4-chlorophenyl)-1-phenylbenzo[4,5]imidazo[1,2-a]-
pyridine (5aae). Yellow-green solid, mp 244−247 °C; yield, 82%
1
(76.1 mg, eluent: EtOAc/petroleum ether = 1/6); H NMR (400
MHz, CDCl3): δ 7.94 (d, J = 8.3 Hz, 1H), 7.64 (br, 5H), 7.47−7.43
(m, 2H), 7.39 (t, J = 7.7 Hz, 1H), 7.21−7.18 (m, 2H), 7.07 (t, J = 8.7
Hz, 2H), 7.00−6.94 (m, 3H), 6.81 (s, 1H), 6.65 (d, J = 8.5 Hz, 1H).
13C{1H} NMR (151 MHz, CDCl3): δ 149.4, 145.6, 140.2, 138.8,
137.5, 134.2, 133.9, 133.8, 133.7, 132.7, 131.0, 130.3, 129.5, 129.2,
129.1, 128.7, 128.6, 125.8, 125.2, 120.7, 120.3, 114.8, 114.6. HRMS
(ESI) m/z: [M + H]+ calcd for C29H19Cl2N2, 465.0920; found
465.0919.
3,4-Bis(4-bromophenyl)-1-phenylbenzo[4,5]imidazo[1,2-a]-
pyridine (5aaf). The reaction was carried out on a 1.0 mmol scale:
yellow-green solid, mp 246−248 °C; yield, 75% (414 mg, eluent:
EtOAc/petroleum ether = 1/6); 1H NMR (400 MHz, CDCl3): δ 7.93
(d, J = 8.3 Hz, 1H), 7.64 (br, 5H), 7.51 (d, J = 8.4 Hz, 2H), 7.42−
7.35 (m, 5H), 7.10 (d, J = 8.4 Hz, 2H), 6.99 (t, J = 7.7 Hz, 1H), 6.78
(s, 1H), 6.64 (d, J = 8.5 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3):
δ 148.2, 144.6, 139.1, 137.6, 136.9, 133.1, 133.0, 131.9, 130.6, 130.5,
130.3, 129.2, 128.4, 128.2, 128.0, 124.7, 124.1, 121.2, 121.0, 119.7,
119.2, 113.7, 113.5. HRMS (ESI) m/z: [M + H]+ calcd for
C29H19Br2N2, 552.9910; found, 552.9910, 554.9885, 556.9863.
1-Phenyl-3,4-bis(4-(trifluoromethyl)phenyl)benzo[4,5]imidazo-
[1,2-a]pyridine (5aag). Yellow-green solid, mp 265−268 °C; yield,
85% (90.4mg, eluent: EtOAc/petroleum ether = 1/6); 1H NMR (400
MHz, CDCl3): δ 7.95 (d, J = 8.3 Hz, 1H), 7.72−7.59 (m, 9H), 7.54
(d, J = 8.2 Hz, 2H), 7.42 (t, J = 7.6 Hz, 1H), 7.35 (d, J = 8.1 Hz, 2H),
7.02 (t, J = 7.8 Hz, 1H), 6.83 (s, 1H), 6.67 (d, J = 8.5 Hz, 1H).
13C{1H} NMR (151 MHz, CDCl3): δ 149.0, 145.6, 142.5, 140.7,
138.8, 134.0, 131.8, 130.1, 130.0 (130. 3, 130. 1, 129.9, 129.6, q, 2JC−F
= 33 Hz), 129.9 (130.2, 130.0, 129.8, 129.5, q, 2JC−F = 33 Hz), 129.5,
129.3, 129.0, 125.9, 125.4, 125.38, 125.36, 125.34, 125.31, 124.1
1
(126.9, 125.1, 123.2, 121.4, q, JC−F = 273 Hz), 123.9 (126.6, 124.8,
123.0, 121.2, q, 1JC−F = 273 Hz), 121.0, 120.4, 114.7, 114.6. 19F NMR
(376 MHz, CDCl3): δ −62.6. HRMS (ESI) m/z: [M + H]+ calcd for
C31H19F6N2, 533.1447; found, 533.1442.
3,4-Bis(3-chlorophenyl)-1-phenylbenzo[4,5]imidazo[1,2-a]-
pyridine (5aah). Yellow-green solid, mp 210−212 °C; yield, 78%
1
(72.4 mg, eluent: EtOAc/petroleum ether = 1/7); H NMR (400
MHz, CDCl3): δ 7.97 (d, J = 8.2 Hz, 1H), 7.67 (br, 5H), 7.54 (s, 1H),
7.43 (t, J = 7.7 Hz, 1H), 7.38−7.30 (m, 4H), 7.29−7.25 (m, 1H),
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Article
7.19 (t, J = 7.8 Hz, 1H), 7.10−7.00 (m, 2H), 6.83 (s, 1H), 6.69 (d, J =
8.5 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3): δ 148.1, 144.5,
139.6, 139.3, 137.7, 135.8, 133.2, 133.1, 133.0, 130.2, 129.2, 128.5,
128.49, 128.4, 128.39, 128.2, 128.0, 127.2, 127.0, 126.8, 124.7, 124.2,
119.8, 119.3, 113.6, 113.5. HRMS (ESI) m/z: [M + H]+ calcd for
C29H19Cl2N2, 465.0920; found, 465.0922.
1-Phenyl-3,4-di(thiophen-2-yl)benzo[4,5]imidazo[1,2-a]pyridine
(5aai). Yellow-green solid, mp 250−252 °C; yield, 72% (58.7 mg,
eluent: EtOAc/petroleum ether = 1/6); 1H NMR (400 MHz,
CDCl3): δ 7.95 (d, J = 8.1 Hz, 1H), 7.69−7.62 (m, 5H), 7.54 (d, J =
5.1 Hz, 1H), 7.40−7.31 (m, 3H), 7.20−7.15 (m, 1H), 7.11 (d, J = 3.6
Hz, 1H), 7.02−6.92 (m, 3H), 6.58 (d, J = 8.5 Hz, 1H). 13C{1H}
NMR (101 MHz, CDCl3): δ 149.9, 145.6, 140.6, 140.0, 135.7, 134.3,
134.1, 130.3, 130.2, 129.6, 129.2, 129.1, 128.3, 128.1, 127.9, 127.4,
127.1, 125.1, 120.8, 120.4, 119.4, 114.4, 114.1. HRMS (ESI) m/z: [M
+ H]+ calcd for C25H17N2S2, 409.0828; found, 409.0827.
layer was extracted with 2 × 5 mL of ethyl acetate. The combined
organic extracts were dried over anhydrous sodium sulfate, filtered,
and concentrated in vacuo. The crude product was then purified by
flash chromatography on silica gel (H), eluting with ethyl acetate/
petroleum ether (1:6).
1-Phenyl-3,4-bis(4-(phenylethynyl)phenyl)benzo[4,5]imidazo-
[1,2-a]pyridine (7). Yellow-green solid, mp 232−235 °C; yield, 45%
1
(53.6 mg, Eluent: EtOAc/petroleum ether = 1/6); H NMR (400
MHz, CDCl3): δ 7.98 (d, J = 8.2 Hz, 1H), 7.73−7.64 (m, 5H), 7.59−
7.52 (m, 8H), 7.49−7.32 (m, 9H), 7.30−7.24 (m, 2H), 7.02 (t, J =
7.8 Hz, 1H), 6.88 (s, 1H), 6.68 (d, J = 8.5 Hz, 1H). 13C{1H} NMR
(151 MHz, CDCl3): δ 149.4, 145.6, 140.1, 139.3, 139.0, 135.4, 134.3,
131.7, 131.7, 131.6, 131.5, 131.4, 130.2, 129.8, 129.5, 129.2, 129.1,
128.5, 128.4, 128.3, 128.2, 126.3, 125.1, 123.4, 123.1, 122.8, 122.6,
120.7, 120.3, 115.0, 114.6, 90.5, 89.9, 89.7, 89.1. HRMS (ESI) m/z:
[M + H]+ calcd for C45H29N2, 597.2325; found, 597.2324.
1-Phenyl-3,4-dipropylbenzo[4,5]imidazo[1,2-a]pyridine (5aaj).
Yellow-green solid, mp 126−128 °C; yield, 48% (31.5 mg, eluent:
EtOAc/petroleum ether = 1/5); 1H NMR (400 MHz, CDCl3): δ 7.93
(d, J = 8.2 Hz, 1H), 7.62−7.53 (m, 5H), 7.36 (t, J = 7.7 Hz, 1H), 6.90
(t, J = 7.8 Hz, 1H), 6.57 (d, J = 8.4 Hz, 1H), 6.51 (s, 1H), 3.20−3.10
(m, 2H), 2.77−2.69 (m, 2H), 1.91−1.82 (m, 2H), 1.76−1.67 (m,
2H), 1.13 (t, J = 7.3 Hz, 3H), 1.04 (t, J = 7.3 Hz, 3H). 13C{1H} NMR
(151 MHz, CDCl3): δ 149.4, 144.0, 139.2, 136.8, 133.7, 128.7, 128.6,
128.2, 127.9, 125.9, 123.5, 118.5, 118.4, 113.8, 113.3, 33.2, 28.6, 22.8,
21.8, 13.5, 13.2. HRMS (ESI) m/z: [M + H]+ calcd for C23H25N2,
329.2012; found, 329.2013.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02126.
1H and 13C NMR spectra of the products and high-
resolution mass spectra of new compounds (PDF)
Ethyl 1,3-diphenylbenzo[4,5]imidazo[1,2-a]pyridine-4-carboxy-
AUTHOR INFORMATION
■
late (5aak). Yellow-green solid, mp 176−179 °C; yield, 79% (61.9
1
Corresponding Authors
mg, eluent: EtOAc/petroleum ether = 1/6); H NMR (400 MHz,
Chunxia Chen − College of Chemistry, Chemical Engineering
and Resource Utilization and Material Science and
Engineering College, Northeast Forestry University, Harbin
150040, P. R. China; Email: ccx1759@163.com
Jinsong Peng − College of Chemistry, Chemical Engineering
and Resource Utilization, Northeast Forestry University,
Harbin 150040, P. R. China; orcid.org/0000-0002-
7822-4560; Email: jspeng1998@nefu.edu.cn
CDCl3): δ 7.96 (d, J = 8.3 Hz, 1H), 7.67−7.60 (m, 7H), 7.55−7.46
(m, 3H), 7.40 (t, J = 7.7 Hz, 1H), 7.10 (s, 1H), 7.02 (t, J = 7.8 Hz,
1H), 6.64 (d, J = 8.5 Hz, 1H), 4.11 (q, J = 7.1 Hz, 2H), 0.99 (t, J = 7.1
Hz, 3H). 13C{1H} NMR (151 MHz, CDCl3): δ 167.3, 148.9, 145.8,
140.1, 135.7, 134.0, 131.2, 130.3, 130.0, 129.6, 129.2, 129.1, 128.5,
128.3, 125.4, 121.4, 120.8, 114.8, 111.7, 61.6, 13.6. HRMS (ESI) m/z:
[M + H]+ calcd for C26H21N2O2, 393.1598; found, 393.1597.
Procedure for the Synthesis of 6. A 10 mL Schlenk tube
equipped with a magnetic stirring bar was charged with 5aaf (110.4
mg, 0.2 mmol), phenylboronic acid (73.2 mg, 0.6 mmol), Pd(OAc)2
(2.2 mg, 0.01 mmol), and Et3N (61 mg, 0.6 mmol), and then, DMF
(1.0 mL) was added to the mixture via a syringe at room temperature.
The vial was sealed and put into a preheated oil bath at 120 °C for 24
h. The mixture was cooled to room temperature, quenched with water
(5 mL), and diluted with ethyl acetate (5 mL). The layers were
separated, and the aqueous layer was extracted with 2 × 5 mL of ethyl
acetate. The combined organic extracts were dried over anhydrous
sodium sulfate, filtered, and concentrated in vacuo. The crude product
was then purified by flash chromatography on a silica gel (H), eluting
with ethyl acetate/petroleum ether (1:7).
Authors
Xin Chen − College of Chemistry, Chemical Engineering and
Resource Utilization and Material Science and Engineering
College, Northeast Forestry University, Harbin 150040, P. R.
China
Peng Sun − College of Chemistry, Chemical Engineering and
Resource Utilization and Material Science and Engineering
College, Northeast Forestry University, Harbin 150040, P. R.
China
Baichuan Mo − College of Chemistry, Chemical Engineering
and Resource Utilization and Material Science and
Engineering College, Northeast Forestry University, Harbin
150040, P. R. China
3,4-Di([1,1′-biphenyl]-4-yl)-1-phenylbenzo[4,5]imidazo[1,2-a]-
pyridine (6). Yellow-green solid, mp 257−259 °C; yield, 83% (91.0
1
mg, eluent: EtOAc/petroleum ether = 1/7); H NMR (400 MHz,
CDCl3): δ 7.96 (d, J = 8.2 Hz, 1H), 7.70−7.60 (m, 11H), 7.57 (d, J =
7.5 Hz, 2H), 7.50 (d, J = 8.2 Hz, 2H), 7.44−7.40 (m, 5H), 7.37−7.31
(m, 4H), 6.98 (t, J = 7.8 Hz, 1H), 6.91 (s, 1H), 6.66 (d, J = 8.4 Hz,
1H). 13C{1H} NMR (151 MHz, CDCl3): δ 148.8, 144.6, 139.9, 139.3,
139.2, 139.1, 138.7, 138.5, 137.2, 133.5, 133.4, 130.8, 129.2, 129.1,
128.5, 128.1, 127.8, 127.7, 126.5, 126.2, 126.1, 125.9, 125.8, 125.5,
123.9, 119.4, 119.2, 114.4, 113.5. HRMS (ESI) m/z: [M + H]+ calcd
for C41H29N2, 549.2325; found, 549.2325.
Procedure for the Synthesis of 7. A 10 mL Schlenk tube
equipped with a magnetic stirring bar was charged with 5aaf (110.4
mg, 0.2 mmol), ethynylbenzene (61.2 mg, 0.6 mmol), PdCl2(PPh3)2
(7 mg, 0.01 mmol), CuI (3.8 mg, 0.02 mmol), and DBU (91.2 mg, 0.6
mmol), and then, DMF (1.0 mL) was added to the mixture via a
syringe at room temperature. The vial was sealed and put into a
preheated oil bath at 120 °C for 24 h. The mixture was cooled to
room temperature, quenched with water (5 mL), and diluted with
ethyl acetate (5 mL). The layers were separated, and the aqueous
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02126
Author Contributions
§X.C. and P.S. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for financial support from the Fundamental
Research Funds for the Central Universities (2572019CG06
and 2572020DR07) and the Natural Science Foundation of
Heilongjiang Province (LC2018003 and B2017002).
M
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