1-alkynyl- and 1-alkenyl-3-arylimidazo[1,5-a]pyridines: Synthesis, photophysical properties, and observation of a linear correlation between the fluorescent wavelength and Hammett substituent constants

Article abstract of DOI:10.1021/jo200864x

1-Alkynyl- and 1-alkenyl-3-arylimidazo[1,5-a]pyridines were synthesized. The Sonogashira coupling of 3-aryl-1-iodoimidazo[1,5-a]pyridines and various terminal alkynes with Pd(PPh₃)₂Cl₂ (10 mol %) and CuI (10 mol %) in triethylamine at 80 °C for 12 h afforded the corresponding 1-alkenyl-3-arylimidazo[1,5-a]pyridines in good to excellent yields. The Mizoroki-Heck reaction of 3-aryl-1-iodoimidazo[1,5-a]pyridines and various styrene derivatives proceeded smoothly with Pd(OAc)₂ (5 mol %), IMes?HCl (10 mol %), and Cs₂CO₃ (2 equiv) in DMA at 130 °C for 20 h to give the alkenylated imidazo[1,5-a]pyridines in moderate to high yields. The fluorescence maxima and fluorescence quantum yields of the alkynylated products were 458-560 nm and Φ_F = 0.08-0.26 in chloroform solution, and those of the alkenylated imidazopyridines were 479-537 nm and Φ_F = 0.03-0.13. The absorption behaviors of the obtained alkynylated and alkenylated imidazo[1,5-a]pyridines showed a good fit to the values predicted by TDDFT calculations at the B3LYP/6-311++G(d,p) level. In addition, the alkynylated imidazo[1,5-a]pyridines obtained showed linear correlations between the Hammett substituent constants of the substituents on the arylalkynyl group and their fluorescence wavelengths.

Full text of DOI:10.1021/jo200864x

ARTICLE
pubs.acs.org/joc
1-Alkynyl- and 1-Alkenyl-3-arylimidazo[1,5-a]pyridines: Synthesis,
Photophysical Properties, and Observation of a Linear Correlation
between the Fluorescent Wavelength and Hammett Substituent
Constants
Eiji Yamaguchi, Fumitoshi Shibahara,* and Toshiaki Murai*
Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan
S Supporting Information
b
ABSTRACT:
1-Alkynyl- and 1-alkenyl-3-arylimidazo[1,5-a]pyridines were synthesized. The Sonogashira coupling of 3-aryl-1-iodoimidazo[1,5-a]-
pyridines and various terminal alkynes with Pd(PPh3)2Cl2 (10 mol %) and CuI (10 mol %) in triethylamine at 80 °C for 12 h
afforded the corresponding 1-alkenyl-3-arylimidazo[1,5-a]pyridines in good to excellent yields. The MizorokiꢀHeck reaction of
3-aryl-1-iodoimidazo[1,5-a]pyridines and various styrene derivatives proceeded smoothly with Pd(OAc)2 (5 mol %), IMes HCl
3
(10 mol %), and Cs2CO3 (2 equiv) in DMA at 130 °C for 20 h to give the alkenylated imidazo[1,5-a]pyridines in moderate to high
yields. The fluorescence maxima and fluorescence quantum yields of the alkynylated products were 458ꢀ560 nm and ΦF =
0.08ꢀ0.26 in chloroform solution, and those of the alkenylated imidazopyridines were 479ꢀ537 nm and ΦF = 0.03ꢀ0.13. The
absorption behaviors of the obtained alkynylated and alkenylated imidazo[1,5-a]pyridines showed a good fit to the values predicted
by TDDFT calculations at the B3LYP/6-311++G(d,p) level. In addition, the alkynylated imidazo[1,5-a]pyridines obtained showed
linear correlations between the Hammett substituent constants of the substituents on the arylalkynyl group and their fluorescence
wavelengths.
The obtained diarylated imidazopyridines showed fluorescent
emission in a wavelength range of 454ꢀ526 nm. In addition, the
quantum yields of 1,3-diarylated imidazopyridines were improved
compared to those of the parent 3-arylated imidazopyridines.
Meanwhile, there is likely no correlation between the photo-
physical properties of these imidazopyridines and the electronic
properties of their substituents. In this context, most biaryl
moieties have twisted structures due to steric repulsion between
their substituents, and this results in the formation of a distorted
π-conjugated system. As a result, the electronic properties of the
substituents do not strongly influence their photophysical prop-
erties. In common with such biaryls, most 1,3-diarylated imidazo-
[1,5-a]pyridines 3 also form distorted π-conjugated systems due
to steric repulsion between the hydrogen atoms at the 4- or
7-positions of imidazo[1,5-a]pyridines and substituted aromatic
’ INTRODUCTION
Imidazo[1,5-a]pyridines are an important class of compounds
that have potential as functional materials1,2 and bioactive com-
pounds.3 Therefore, the development of methods for the synth-
esis ofimidazo[1,5-a]pyridine derivatives has recently attracted con-
siderable attention.4ꢀ6 As part of our investigation of the synthesis
and photophysical properties of multifunctional imidazo[1,5-a]-
pyridines, we recently reported a synthesis of diverse 1,3-diarylated
imidazo[1,5-a]pyridine derivatives 3 using cross-coupling reac-
tions of 1-halogenated 3-aryl-imidazo[1,5-a]pyridines 1 and organo-
metallic reagents 2 (eq 1).7
Received: April 28, 2011
Published: June 22, 2011
r
2011 American Chemical Society
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ARTICLE
rings, as suggested by X-ray analyses7,8 and DFT calculations9
(Figure 1, left). Our subsequent interest in the substituent effects
on the photophysical properties of imidazo[1,5-a]pyridines led
us to further investigate the formation of undistorted π-conjugated
systems with two aryl groups on imidazopyridines (Figure 1).
For this purpose, π-conjugated spacers, such as ethynylene and
ethenylene groups, have usually been introduced into ArꢀAr
moieties.10
properties of the resulting imidazo[1,5-a]pyridine derivatives
were also investigated. During our investigations, we found a
linear correlation between the Hammett substituent constants of
introduced substituents on arylalkynyl groups and the emission
wavelength.
’ RESULTS AND DISCUSSION
Meanwhile, straightforward methods for obtaining alkyny-
lated and alkenylated imidazo[1,5-a]pyridines have not been
well-established. Transition-metal-catalyzed cross-coupling
reactions of aryl halides with terminal alkynes (Sonogashira
coupling)11 and alkenes (MizorokiꢀHeck reaction)12 are
some of the most versatile methods for introducing alkynyl
and alkenyl moieties, respectively, into aromatic compounds.
Many reviews regarding these reactions are available. However,
there are few examples of the use of electron-rich nitrogen-
containing heteroarenes as one or both of the substrates in cross-
coupling reactions,13 since electron-rich heteroaryl metal species,
even heteroarylꢀtransition metal intermediates in these pro-
cesses, are often unstable and readily undergo protonolysis or
decomposition under the reaction conditions.14 Therefore,
further optimization of the reaction conditions is essential if we
wish to use these reactions to synthesize alkynyl- and alkenyl-
imidazopyridines. In this report, we describe the synthesis of
imidazo[1,5-a]pyridines that contain alkynyl or alkenyl groups to
establish tunable photofunctional materials by means of Sonoga-
shira coupling and MizorokiꢀHeck reaction. The photophysical
Synthesis of 1-Alkynylated Imidazo[1,5-a]pyridines by
Sonogashira Coupling Reaction. The results of the initial
screening of the reaction conditions for the Sonogashira
coupling of halogenated imidazopyridines 1a and phenylacety-
lene 5a are shown in Table 1. The reaction of 1-bromo-3-
phenylimidazo[1,5-a]pyridine 1aBr with phenylacetylene (5a)
(2 equiv), HN(i-Pr)2 (2 equiv) and a catalytic amount of
Pd(PPh3)2Cl2 (10 mol %) and CuI (10 mol %) in dioxane did
not give any products at all (entry 1).15 The use of P(t-Bu)3 as a
ligand, which effectively facilitated the SuzukiꢀMiyaura coupling
reaction of a series of imidazopyridyl halides, perhaps due to
acceleration of the oxidative addition of such electron-rich
halides, was not effective (entry 2).7b The desired alkynylated
product 4aa was obtained when Pd(PPh3)4 was used as a catalyst
(entry 3), and the use of acetonitrile as a solvent slightly
improved the yield of 4aa (entry 4). The reaction of 1aI with
Pd(PPh3)2Cl2 as a catalyst in Et3N gave 4aa in better yield (entry
5), and thus we chose these reaction conditions for further
investigations.
The scope of suitable substrates in the Sonogashira coupling
of 1 was then examined. The results are summarized in Table 2.
The reaction tolerated a variety of substituents on the terminal
alkynes, such as 4-methoxyphenyl (PMP) (5b), 4-trifluoro-
methylphenyl (5c), 2-pyridyl (5d), 1-naphthyl (5e), silyl (5f
and 5g), alkenyl (5h), and alkyl (5i) groups, to give the
coupling products in moderate to high yields (entries 1ꢀ9).
In addition, a prolonged reaction time improved the yield of the
products in some of the reactions (e.g., entry 5). The reaction of
electron-donating 4-methoxyphenyl substituted iodoimidazo-
[1,5-a]pyridines 1bI and terminal alkynes 5 gave the corre-
sponding products 4b in good yields (entries 10ꢀ14). The
reaction also proceeded with the use of electron-deficient
substrates such as trifluoromethylphenyl- (1cI) and fluorophe-
nyl- (1dI) imidazopyridines (entries 15ꢀ22). The coupling
Figure 1. Steric repulsion in 3a and the planar structure of 4aa and the
optimized structures of 3a and 4aa calculated at the B3LYP/6-31G level.
Table 1. Optimization of the Sonogashira Coupling of 1a and 5a
entry
X
cat.
ligand
base
conditions
4aa yield (%)a
1
2
3
4
5
Br
Br
Br
Br
I
Pd(PPh3)2Cl2
Pd(MeCN)2Cl2
Pd(PPh3)4
none
HN(i-Pr)2
HN(i-Pr)2
EtN(i-Pr)2
EtN(i-Pr)2
none
dioxane, rt, 17 h
no reaction
P(t-Bu)3 HBPh4
dioxane, rt, 24 h
no reaction
3
none
none
none
dioxane, 60 °C, 20 h
MeCN, 60 °C, 20 h
Et3N, 80 °C, 12 h
53
Pd(PPh3)4
60
65b
Pd(PPh3)2Cl2
a Isolated yield. b The reaction was carried out with 1.3 equiv of 5a.
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Table 2. Reaction of Various Terminal Alkynes 5 with Halogenated Imidazopyridine Derivatives 1a
entry
Ar
R
product
yield (%)
entry
Ar
R
product
yield (%)
1
Ph
Ph
4aa
4ab
4ac
4ad
4ae
4af
65
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
4-FC6H4
2-pyridyl
1-Naph
4dd
4de
4ea
4eb
4ec
4ed
4ef
72
90
86
84
91
91
59
99
99
99c
87
87d
63c
83
81
76
77
73
70
2
PMP
64
3
4-CF3C6H4
2-pyridyl
1-Naph
TMS
99
2-pyridyl
Ph
4
84
69 (85)b
PMP
5
4-CF3C6H4
2-pyridyl
1-naphtyl
4-FC6H4
4-ClC6H4
4-MeC6H4
4-NMe2C6H4
2-HC(O)C6H4
2-MeOC6H4
2-MeSC6H4
Ph
6
88
7
TES
4ag
4ah
4ai
80
8
1-cyclohexenyl
C5H11
Ph
73
4ej
9
81
4ek
4el
10
11
12
13
14
15
16
17
18
19
20
PMP
4ba
4bb
4bd
4be
4bf
4ca
4cb
4 cd
4ce
4da
4db
79
PMP
77
4em
4en
4eo
4ep
4fa
2-pyridyl
1-Naph
TMS
69
80
99
4-CF3C4H4
4-FC6H4
Ph
82
2-thienyl
PMP
74
4-CF3C6H4
4-FC6H4
4-ClC6H4
4-MeC6H4
4 fc
4fj
2-pyridyl
1-Naph
Ph
71
99
4fk
4fl
99
PMP
75
a Isolated yields. b The reaction was performed for 14 h. c The reaction was performed at 60 °C for 4 h. d The reaction was performed at 60 °C
for 5 h.
reaction was not disturbed by the use of 2-pyridylimidazopyridine
1eI as a substrate, which may act as a bidentate ligand for the
catalyst and could not be used in KumadaꢀTamaoꢀCorriu
couplings.7b As a result, the reaction of 1eI and various terminal
alkynes 5 took place to give 4 in good to high yields (entries
23ꢀ34), even with an arylacetylene bearing a formyl group (5h).
The coupling reaction of imidazopyridines bearing electron-rich
heteroaromatics such as 2-thienylimidazopyridine 1fI also pro-
ceeded to give the corresponding products 4f in good yields
(entries 35ꢀ39).
desilylated products 10a and 10b in respective yields of 74%
and 88%. Next, 10a and 10b were treated with iodoimidazo-
pyridine 1cI in the presence of a catalytic amount of Pd-
(PPh3)2Cl2 and CuI in Et3N at 80 °C for 16 h to give the
unsymmetric bis-imidazopyridines 11a and 11b in moderate
yields.
We then focused on the synthesis of bis-imidazo[1,5-a]-
pyridines linked by a π-conjugated spacer such as benzene- and
fluorine-based bis-ethynylene.16 Under the optimized reaction
conditions, the reactions of 1aI and diethynylbenzene 6 or
diethynylfluorene 8 gave the corresponding bis-imidazopyri-
dine 7 and 9 in respective yields of 52% and 48% (eqs 2 and 3).
Additionally, the synthesis of direct ethynylene-bridged un-
symmetric bis-imidazopyridines, which are expected to form a
donorꢀacceptor system, was carried out as follows (eq 4).
First, the treatment of 4af and 4bf with tetrabutylammonium
fluoride (TBAF) in THF at room temperature led to the
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Table 3. Optimization of the MizorokiꢀHeck Reaction with
1 and 12
a Isolated yield. b The reaction was carried out with 2 equiv of styrene.
c The reaction was carried out with 20 mol % of PPh3.
Photophysical Properties of Imidazo[1,5-a]pyridine Deri-
vatives. UVꢀvis and fluorescence spectra of the obtained
imidazopyridine derivatives were measured. Selected results are
listed in Table 5.18 The photophysical properties of the alkyny-
lated imidazo[1,5-a]pyridines indicated that the arylalkynyl
groups clearly influence the absorption and emission maxima
(λabs and λem) and fluorescence quantum yields (entries 3ꢀ21).
As expected, in a series of 3-phenylimidazopyridines such as
14a, 3a, and 4aa, the longest λabs values of 1-phenylethynyl-3-
phenylimidazopyridine 4aa were red-shifted (14a 317 nm, 3a
388 nm vs 4aa 397 nm, entries 1 and 2 vs 3), since the formation
of the extended planar π-conjugated system leads to a smaller
HOMOꢀLUMO band gap. The absorption and emission of
alkenylated imidazopyridine 13aa were also significantly red-
shifted (λabs 425 nm, λem 536 nm) compared to those of the
parent 14a and 3a (entry 26). To understand this observation,
DFT and TDDFT calculations were performed for a series of
imidazopyridines at the B3LYP level with a 6-311++G(d,p) basis
set. As a result, the HOMOꢀLUMO band gaps narrowed and
the predicted absorption wavelength increased in the order 14a,
3a, 4aa, and 13aa (Figure 2, left).19 These results are consistent
with the experimental observations. Aryl groups at the C3
position of 4 had less of an effect on their absorptions, emissions,
and quantum yields (entries 3, and 6—9) as in 14 and 3. In
contrast, the electronic properties of the substituents on the
arylalkynyl groups of 4 clearly influence their photophysical
properties. For instance, 2-pyridylimidazopyridines 4e bearing
electron-rich alkynes show red-shifted emissions based on 4ea
(entries 9 vs 10, 14 and 15). On the other hand, electron-poor
alkynes show blue-shifted emissions (entries 9 vs 11, 12, and 13).
Synthesis of 1-Alkenylated Imidazo[1,5-a]pyridines by the
MizorokiꢀHeck Reaction. To introduce arylalkenyl groups into
imidazopyridines, the MizorokiꢀHeck reaction of 1 and terminal
alkene 12 was examined. The optimization of the reaction condi-
tions is displayed in Table 3. The reaction of 1eBr with styrene
12a, Cs2CO3, and a catalytic amount of Pd(OAc)2 in DMA at
100 °C for 20 h did not give the product at all (entry 1).12 In
contrast, the reaction took place with the use of 1eI instead of
bromide 1eBr and PPh3 as a ligand to give the product 13ea in
56% yield (entry 2). The use of an electron-rich ligand such as
P(t-Bu)3 improved the yield of 13ea (entry 3). Use of the N-
heterocyclic carbene (NHC) precursor IPr HCl (14a) also
3
promoted the reaction, but the yield was moderate (entry 4),17
whereas the precursor bearing mesityl groups IMes HCl (14b)
3
served as a suitable ligand for the reaction and gave the corre-
sponding product 13ea in high yield (entry 5).
With the conditions in hand, the reactions of iodinated
imidazo[1,5-a]pyridines 1I and a series of styrene derivatives 12
were carried out. The results are listed in Table 4. The reaction of
3-phenyl-1-iodoimidazo[1,5-a]pyridine and styrene derivatives
(12a and 12b) under the optimized conditions gave the alkeny-
lated products 13aa and 13ac in respective yields of 55% and
54%. The reaction of electron-rich heteroaryl iodide 1bI and 12a
gave the corresponding product 13ba in moderate yield. Mean-
while, the treatment of both iodoimidazopyridines bearing
electron-deficient groups 1cI and a heteroarene 1eI with 12a
afforded the coupling products 13ca and 13ea in good yields.
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Table 4. Reactions of Various Styrenes 12 and Imidazopyr-
idine Derivatives 1
of the substituents on arylalkynyl groups directly affected the
imidazopyridine ring of 4 via an undistorted planar π-conjugated
system, which efficiently resulted in a linear correlation between
emission and the substituent constants.22 Futhermore, the photo-
physical properties such as absorption and emission behaviors
are consistent with the results regarding HOMOꢀLUMO gaps
calculated by DFT calculations and the absorption behaviors
predicted by TDDFT calculations, which should also be related
to emission behavior (e.g., Figure 2, right).24 Meanwhile, most of
the peak tops of the longest UVꢀvis absorptions of alkynylated
imidazopyridines 4 were indistinct, since the peaks are immersed
in adjacent larger absorptions, and this is probably why the series
of alkynylated imidazopyridines 4 did not show an ordered
correlation between the observed longest UVꢀvis absorptions
and the substituents (e.g., Figure S2 in Supporting Information).
Imidazopyridine dimers bearing benzene- and fluorene-based
spacers 7 and 9 had a similar λem as 4aa, while stronger UV
absorption and slightly improved ΦF were observed (entries 3 vs
22 and 23). Ethynylene-bridged dimers 11a and 11b show a
similar UV absorption wavelength (329 and 330 nm) but a red-
shifted fluorescent emission wavelength (501 and 506 nm)
compared with 4aa (entries 3 vs 24 and 25).
’ CONCLUSION
In conclusion, we have synthesized 1-alkynyl- and 1-alkenyl-
imidazo[1,5-a]pyridines by means of Sonogashira coupling and
MizorokiꢀHeck reaction and investigated their photophysical
properties. All of the imidazopyridine derivatives obtained exhibited
fluorescence in solution. The fluorescence maxima and fluores-
cence quantum yields of the alkynylated products were 458ꢀ560 nm
and ΦF = 0.08ꢀ0.26 in chloroform solution. Furthermore, the
fluorescence maxima and fluorescence quantum yields of the
alkenylated imidazopyridines were 479ꢀ537 nm and ΦF = 0.03ꢀ
0.13, respectively. The alkynylated imidazopyridines 4 obtained
show linear correlations between the Hammett substituent
constants of the substituents on the arylalkynyl group and their
fluorescence wavelength. On the basis of this predictable prop-
erty, a series of alkynylated imidazopyridines may have potential
as tunable fluorescent materials. Further investigations of the
properties and applications of imidazo[1,5-a]pyridine derivatives
are underway.
’ EXPERIMENTAL SECTION
General. The 1H NMR (400 MHz), 13C NMR (100 MHz), and 19
F
NMR (376 MHz) spectra were recorded in CDCl3. Chemical shifts of
1H and 13C were reported in δ values referenced to tetramethylsilane
and CDCl3 as internal standards, respectively. The 19F chemical shifts are
expressed in δ values deshielded with respect to CF3COOH as an external
standard. Themassspectra(MS) andhighresolutionmassspectra(HRMS)
were obtained by ionizing samples via electron ionization (70 eV).
Materials. Unless otherwise noted, reagents were obtained com-
mercially and used without purification. Terminal alkynes 5k,25 5l,26 8,27
and imidazo[1,5-a]pyridine derivatives 17b were prepared according to
the literature. Compound 6 was prepared according to a modified pro-
cedure in the literature.27 Silica gel 60N (spherical, neutral, 40ꢀ50 mm)
from Kanto Chemical Co., Inc. was used in flash column chromatography.
Synthesis of 1-Iodoimidazo[1,5-a]pyridine (1).
a Isolated yield.
Dramatically red-shifted emission was observed with imidazo-
pyridines bearing a 2-formyl-phenylethynyl group 4en (560 nm,
entry 16). During our investigation of the electronic influences of
the alkynyl substituents at the 1-position, we found that the λem values
of 3-phenylimidazopyridine derivatives 4a have a linear correla-
tion with the Hammett substituent constants of the substituents
on the arylalkynyl group, as shown in Figure 3.20 Similar correlations
were also found with 3-(2-pyridyl)- 4e and 3-(2-thienyl)imidazo-
pyridine 4f derivatives. In contrast, 1,3-diarylated imidazopyridines
3 likely showed no trend in the emission wavelength (Figure 3,
lower right).21 These observations imply that the electronic influence
1-Iodo-3-(2-thienyl)imidazo[1,5-a]pyridine (1fI). To a solu-
tion of 3-(2-thienyl)imidazo[1,5-a]pyridine (0.30 g, 1.5 mmol) in THF
(3 mL) was added iodine (0.42 g, 1.7 mmol, 1.1 equiv) at room
temperature under an Ar atmosphere. The resulting mixture was stirred
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Table 5. Selected Photophysical Properties of the Obtained Imidazo[1,5-a]pyridines
UVꢀvisa
fluorescencea
UVꢀvisa
fluorescencea
b
b
entry
1
λabs (nm)
log ε
λem (nm)
ΦF
entry
14
λabs (nm)
log ε
λem (nm)
ΦF
14a
3a
317
4.25
461
0.07
0.16
0.23
4el
407
370
332
410
379
339
420
398
371
287
405
369
337
399
363
348
399
370
333
397
343
4.01
4.42
4.42
4.09
4.37
4.43
4.20
4.30
4.40
3.43
3.91
4.30
4.50
4.16
4.44
4.52
3.97
4.29
4.43
3.96
4.41
460
0.19
0.07
0.20
2
3
388
345
306
397
333
320
3.45
3.88
4.14
3.78
4.41
4.40
477
478
15
16
4em
4en
476
560
4aa
4
5
6
7
4ab
4ac
4ba
4ca
387
331
315
416
373
344
398
335
321
411
355
330
317
377
332
318
3.91
4.56
4.60
3.70
4.26
4.49
3.81
4.43
4.45
3.50
4.32
4.43
4.36
3.93
4.40
4.41
485
465
488
473
0.23
0.21
0.20
0.16
17
18
19
20
4fa
4 fc
4fj
490
483
489
487
0.06
0.08
0.07
0.07
4fk
8
4da
478
0.25
21
4fl
402
3.74
493
0.08
371
335
405
342
4.05
4.28
4.62
4.64
9
4ea
4eb
4ec
410
368
331
410
370
330
410
387
369
3.93
4.55
4.36
3.88
4.44
4.36
4.18
4.52
4.60
459
464
447
0.15
0.15
0.19
22
23
24
7
479
476
501
0.26
0.26
0.15
10
11
9
409
4.80
379
407
329
318
295
405
330
318
298
425
346
4.77
4.21
4.45
4.42
4.34
4.19
4.45
4.45
4.40
3.73
4.42
11a
12
13
4ej
409
367
330
3.90
4.48
4.48
458
455
0.19
0.07
25
26
11b
506
536
0.16
0.03
4ek
410
389
367
336
4.04
4.42
4.53
4.47
13aa
a Measured in CHCl3 (10ꢀ5 M). b Quantum yields (ΦF) were determined with reference to quinine sulfate in 0.1 M aqueous sulfuric acid (excited at
350 nm).
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Figure 2. Energy levels of the HOMO and LUMO and the absorption wavelength predicted by TDDFT calculations of compounds 14a, 3a, 4, and 13aa
at the B3LYP/6-311++G(d,p) level.
Figure 3. Correlations between λem and Hammett substituent constants23 of 4a, 4e, 4f, and 3a.
at 40 °C for 15 h. The reaction mixture was quenched with saturated
Na2S2O3 aq, neutralized with NaHCO3 aq, and extracted with CH2Cl2
(10 mL ꢁ 3). The combined organic layers were dried over MgSO4,
filtered, and concentrated in vacuo. The residue was purified by flash
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column chromatography on silica gel (n-hexane/EtOAc = 4:1) to give
1-iodo-3-(2-thienyl)imidazo[1,5-a]pyridine (0.25 g, 52%) as a yellow
solid. Mp 104ꢀ105 °C, Rf = 0.43 (n-hexane/EtOAc = 4:1); IR (KBr)
(d, J = 7.3 Hz, 1H), 8.58 (d, J = 8.8 Hz, 1H). 13C NMR (CDCl3) δ 87.6,
90.9, 114.1, 115.1, 118.8, 121.0, 121.3, 122.1, 125.4, 126.4, 126.5, 126.7,
128.3, 128.3, 129.1, 129.2, 129.5, 130.1, 132.1, 133.0, 133.2, 134.5, 138.5.
MS (EI) m/z 344 (M+); HRMS (EI) calcd for C25H16N2 (M+) 344.1313,
found 344.1321.
3096, 2916, 1738, 1628, 1498, 1401, 1359, 1262 cmꢀ1 1H NMR
.
(CDCl3) δ 6.67 (dd, J = 7.3, 6.8 Hz, 1H), 6.80 (dd, J = 8.8, 6.8 Hz,
1H), 7.16 (dd, J = 4.9, 3.4 Hz, 1H), 7.34 (d, J = 9.3 Hz, 1H), 7.41 (d, J =
4.9 Hz, 1H), 7.48 (d, J = 3.4 Hz, 1H), 8.26 (d, J = 7.3 Hz, 1H). 13C NMR
(CDCl3) δ 74.3, 114.5, 118.9, 120.2, 122.1, 125.3, 126.4, 127.6, 131.1,
133.5, 135.1. MS (EI) m/z 326 (M+); HRMS (EI) calcd for C11H7IN2S
(M+) 325.9375, found 325.9371.
1-(Trimethylsilyl)ethynyl-3-phenylimidazo[1,5-a]pyridine
(4af). Brown oil. Rf = 0.50 (n-hexane/EtOAc = 4:1); IR (neat) 2943,
2863, 2145, 1604, 1510, 1461, 1407, 1353, 1317, 1129, 1075, 997,
694 cmꢀ1. 1H NMR (CDCl3) δ 0.29 (s, 9H), 6.63 (dd, J = 7.3, 6.8 Hz,
1H), 6.67 (dd, J = 9.3, 6.8 Hz, 1H), 7.44ꢀ7.53 (m, 3H), 7.63 (d, J = 9.3 Hz,
1H), 7.79 (d, J = 7.3 Hz, 2H), 8.24 (d, J = 7.3 Hz, 1H). 13C NMR
(CDCl3) δ ꢀ0.03, 97.8, 97.9, 114.0, 114.9, 118.8, 120.9, 122.0, 128.2,
129.0, 129.1, 129.5, 134.8, 138.0. MS (EI) m/z 290 (M+); HRMS (EI)
calcd for C18H18N2Si (M+) 290.1239, found 290.1246.
General Procedure for Sonogashira Coupling of 1 and 5.
Into an oven-dried screw-capped reaction tube were placed Pd(PPh3)2-
Cl2 (10 mol %), CuI (10 mol %), 1-iodo-3-arylimidazo[1,5-a]pyridine 1
(0.25 mmol), terminal alkyne 5 (1.3 equiv) and triethylamine (1 mL).
The reaction tube was flushed with Ar, and the resulting solution was
then heated at 80 °C and stirred for the reaction period. The mixture was
cooled at room temperature and purified by flash column chromatog-
raphy on silica gel (n-hexane/EtOAc) to give the coupling product 4.
1-Phenylethynyl-3-phenylimidazo[1,5-a]pyridine (4aa).
Yellow solid. Mp 156ꢀ158 °C, Rf = 0.35 (n-hexane/EtOAc = 4:1); IR
1-(Triethylsilyl)ethynyl-3-phenylimidazo[1,5-a]pyridine
(4ag). Brown oil. Rf = 0.50 (n-hexane/EtOAc = 4:1); IR (neat) 2957,
1
2360, 2145, 1629, 1518, 1350, 1246, 1126, 1073, 843, 748 cmꢀ1. H
NMR (CDCl3) δ 1.11 (s, 15H), 6.63 (dd, J = 7.8, 6.3 Hz, 1H), 6.87 (dd,
J = 9.3, 6.3 Hz, 1H), 7.45ꢀ7.53 (m, 3H), 7.61 (d, J = 9.3 Hz, 1H), 7.78
(d, J = 7.3 Hz, 2H), 8.23 (d, J = 7.8 Hz, 1H). 13C NMR (CDCl3) δ 11.3,
18.7, 94.1, 99.6, 113.9, 115.3, 118.8, 120.8, 121.9, 128.3, 128.9, 129.1,
129.5, 135.2, 137.8. MS (EI) m/z 332 (M+); HRMS (EI) calcd for
C21H24N2Si (M+) 332.1709, found 332.1716.
1
(KBr) 2203, 1597, 1522, 1487, 1352, 1212, 1126, 756, 693 cmꢀ1. H
NMR (CDCl3) δ 6.59 (dd, J = 7.2, 6.3 Hz, 1H), 6.83 (dd, J = 8.8, 6.3 Hz,
1H), 7.24ꢀ7.30 (m, 3H), 7.37ꢀ7.48 (m, 3H), 7.53 (d, J = 7.1 Hz, 2H),
7.65 (d, J = 8.8 Hz, 1H), 7.76 (d, J = 8.3 Hz, 2H), 8.21 (d, J = 7.2 Hz, 1H).
13C NMR (CDCl3) δ 82.7, 92.7, 114.1, 115.0, 118.9, 120.8, 122.1, 123.6,
127.9, 128.2, 128.3, 129.1, 129.2, 129.6, 131.4, 134.3, 138.4. MS (EI) m/z
294 (M+); HRMS (EI) calcd for C21H14N2 (M+) 294.1157, found
294.1158.
1-(4-Methoxyphenyl)ethynyl-3-phenylimidazo[1,5-a]pyridine
(4ab). Yellow solid. Mp 129ꢀ130 °C, Rf = 0.25 (n-hexane/EtOAc = 2:1); IR
(KBr) 2834, 2359, 2203, 1602, 1521, 1502, 1439, 1245, 1171, 1125, 836, 746,
694 cmꢀ1. 1H NMR (CDCl3) δ 3.83 (s, 3H), 6.63 (dd, J = 7.3, 6.3 Hz, 1H),
6.86 (dd, J = 9.3, 6.3 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 7.43ꢀ7.55 (m, 5H),
7.69 (d, J = 9.3 Hz, 1H), 7.82 (d, J = 6.8 Hz, 2H), 8.26 (dd, J = 7.3 Hz, 1H),
13C NMR (CDCl3) δ 55.5, 81.4, 92.8, 114.3, 115.6, 116.0, 119.2, 120.8, 122.3,
128.5, 129.3 (two carbon atoms were overlapped), 129.4, 129.9, 133.2, 134.3,
138.5, 159.8. MS (EI) m/z 324 (M+); HRMS (EI) calcd for C22H16N2O
(M+) 324.1263, found 324.1263.
1-(4-Trifluoromethylphenyl)ethynyl-3-phenylimidazo-
[1,5-a]pyridine (4ac). Yellow solid. Mp 187ꢀ189 °C, Rf = 0.50
(n-hexane/EtOAc = 1:1); IR (KBr) 2976, 2960, 2201, 1609, 1562,
1325 cmꢀ1. 1H NMR (CDCl3) δ 6.67 (dd, J = 7.3, 6.3 Hz, 1H), 6.92 (dd,
J = 9.0, 6.3 Hz, 1H), 7.47 (t, J = 7.3 Hz, 1H), 7.53 (t, J = 7.3 Hz, 2H), 7.60
(d, J = 8.3 Hz, 2H), 7.67ꢀ7.71 (m, 3H), 7.81 (d, J = 8.8 Hz, 2H), 8.28
(d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ 85.5, 91.6, 114.2, 118.6, 121.4,
122.2, 124.0 (q, JCꢀF = 272.1 Hz), 125.2 (q, JCꢀF = 3.3 Hz), 127.5, 128.2,
129.1, 129.3, 129.4 (q, JCꢀF = 33.3 Hz), 131.3, 133.6, 133.8, 134.9, 138.7.
19F NMR (CDCl3) δ ꢀ63.0. MS (EI) m/z 362 (M+). HRMS (EI) calcd
for C22H22F3N2 (M+) 362.1031, found 362.1028.
1-(2-Pyridyl)ethynyl-3-phenylimidazo[1,5-a]pyridine (4ad).
Yellow solid. Mp 132ꢀ134 °C, Rf = 0.22 (n-hexane/EtOAc = 4:1); IR
(KBr) 2359, 2341, 2202, 1580, 1558, 1508, 1465, 1428, 1350, 1126,
1068, 775, 695 cmꢀ1. 1H NMR (CDCl3) δ 6.60 (dd, J = 7.8, 7.3 Hz, 1H),
6.93 (dd, J = 9.3, 7.3 Hz, 1H), 7.21 (dd, J = 7.8, 4.9 Hz, 1H), 7.44ꢀ7.69
(m, 5H), 7.80ꢀ7.83 (m, 3H), 8.29 (d, J = 7.3 Hz, 1H), 8.60 (d, J =
4.9 Hz, 1H). 13C NMR (CDCl3) δ 83.2, 92.3, 113.5, 113.9, 118.6,
121.2, 121.8, 121.9, 126.7, 127.9, 128.1, 128.7, 128.9, 135.0, 135.8,
136.4, 143.5, 149.5. MS (EI) m/z 295 (M+); HRMS (EI) calcd for
C20H13N3 (M+) 295.1109, found 295.1104.
1(1-Cyclohexyenyl)ethynyl-3-phenylimidazo[1,5-a]pyri-
dine (4ah). Brown oil. Rf = 0.55 (n-hexane/EtOAc = 4:1); IR (neat)
2927, 2362, 2169, 1633, 1509, 1445, 1354, 1301, 1172, 1124, 1075, 951,
1
916, 771, 728, 695 cmꢀ1. H NMR (CDCl3) δ 1.60ꢀ1.72 (m, 4H),
2.13ꢀ2.19 (m, 2H), 2.27ꢀ2.32 (m, 2H), 6.26 (tt, J = 4.2, 2.0 Hz, 1H),
6.60 (dd, J = 7.3, 6.3 Hz, 1H), 6.82 (dd, J = 9.0, 6.3 Hz, 1H), 7.4ꢀ7.53
(m, 3H), 7.61 (d, J = 9.0 Hz, 1H), 7.79 (d, J = 7.1 Hz, 2H), 8.23 (d, J = 7.3
Hz, 1H). 13C NMR (CDCl3) δ 21.5, 22.3, 25.7, 29.2, 79.6, 94.4, 113.8,
115.4, 118.8, 120.2, 120.8, 121.8, 128.1, 128.9, 128,9, 129.5, 133.7, 134.4,
138.0. MS (EI) m/z 298 (M+); HRMS (EI) calcd for C21H18N2 (M+)
298.1470, found 298.1483.
1-(1-Heptynyl)-3-phenylimidazo[1,5-a]pyridine (4ai).
Brown oil. Rf = 0.90 (n-hexane/EtOAc = 4:1); IR (neat) 3065, 2932,
2858, 2361, 2329, 1602, 1461, 1358, 1300, 1189, 957, 773, 745,
696 cmꢀ1. 1H NMR (CDCl3) δ 0.92 (t, J = 7.3 Hz, 3H), 1.36 (quint,
J = 6.8 Hz, 2H), 1.48 (tq, J = 7.3, 6.8 Hz, 2H), 1.66 (quint, J = 6.8 Hz,
2H), 2.51 (t, J = 6.8 Hz, 2H), 6.59 (d, J = 7.3, 6.3 Hz, 1H), 6.80 (d, J = 8.3,
6.3 Hz, 1H), 7.1ꢀ7.52 (m, 3H), 7.59 (d, J=8.3 Hz, 1H), 7.78(d, J=8.3Hz,
2H), 8.23 (d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ 14.0, 19.7, 22.2,
28.5, 31.1, 73.1, 93.6, 113.7, 115.7, 118.8, 119.9, 121.7, 128.1, 128.8,
128.9, 129.6, 133.5, 137.5. MS (EI) m/z 288 (M+); HRMS (EI) calcd for
C20H20N2 (M+) 288.1626, found 288.1622.
1-Phenylethynyl-3-(4-methoxyphenyl)imidazo[1,5-a]pyri-
dine (4ba). Yellow solid. Mp 181ꢀ182 °C, Rf = 0.40 (n-hexane/
EtOAc = 2:1); IR (KBr) 2360, 2199, 1607, 1528, 1510, 1486, 1464,
1257, 1182, 1020, 835, 744, 688 cmꢀ1. 1H NMR (CDCl3) δ 3.86 (s, 3H),
6.60 (dd, J = 7.3, 6.3 Hz, 1H), 6.84 (dd, J = 8.3, 6.3 Hz, 1H), 7.04 (d, J = 8.8
Hz, 2H), 7.30ꢀ7.37 (m, 3H), 7.59 (d, J = 7.8 Hz, 2H), 7.67 (d, J = 8.3
Hz, 1H), 7.73 (d, J = 8.8 Hz, 2H), 8.18 (d, J = 7.3 Hz, 1H). 13C NMR
(CDCl3) δ 55.3, 82.8, 92.6, 113.8, 114.4, 114.5, 118.7, 120.5, 121.9,
122.0, 123.6, 127.8, 128.3, 129.6, 131.3, 134.1, 138.4, 160.0. MS (EI) m/z 324
(M+); HRMS (EI) calcd for C22H16N2O (M+) 324.1263, found 324.1264.
1-(4-Methoxyphenyl)ethynyl-3-(4-methoxyphenyl)imi-
dazo[1,5-a]pyridine (4bb). Yellow solid. Mp 177ꢀ178 °C, Rf =
0.15 (n-hexane/EtOAc = 2:1); IR (KBr) 2833, 2360, 2201, 1603, 1528,
1503, 1461, 1351, 1288, 1245, 1181, 1105, 835 cmꢀ1. 1H NMR (CDCl3)
δ 3.82 (s, 3H), 3.86 (s, 3H), 6.59 (dd, J = 7.3, 6.8 Hz, 1H), 6.81 (dd, J =
9.3, 6.8 Hz, 1H), 6.88 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 7.53
(d, J = 8.8 Hz, 2H), 7.65 (d, J = 9.3 Hz, 1H), 7.73 (d, J = 8.8 Hz, 2H), 8.18
(d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ 55.2, 55.3, 81.3, 92.4, 113.7,
1-(1-Naphthyl)ethynyl-3-phenyl-imidazo[1,5-a]pyridine
(4ae). Yellow solid. Mp 129ꢀ130.5 °C, Rf = 0.30 (n-hexane/EtOAc =
4:1); IR (KBr) 2359, 2341, 1558, 1506, 1457, 1247, 1029, 803, 743,
1
689 cmꢀ1. H NMR (CDCl3) δ 6.65 (dd, J = 7.2, 6.8 Hz, 1H), 6.92
(dd, J = 8.8, 6.8 Hz, 1H), 7.44ꢀ7.62 (m, 6H), 7.77ꢀ7.87 (m, 6H), 8.26
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113.9, 114.4, 114.8, 115.8, 118.8, 120.2, 121.9, 122.0, 129.6, 132.8, 133.7,
138.2, 159.4, 160.2. MS (EI) m/z 354 (M+); HRMS (EI) calcd for
C23H18N2O2 (M+) 354.1368, found 354.1366.
(n-hexaneEtOAc = 4:1); IR (KBr) 2360, 2341, 2199, 1616, 1582, 1514,
1411, 1324, 1159, 1123, 1066, 924, 851 cmꢀ1. 1H NMR (CDCl3) δ 6.76
(dd, J = 7.8, 6.8 Hz, 1H), 6.97 (dd, J = 9.3, 6.8 Hz, 1H), 7.23 (dd, J = 7.8,
4.8 Hz, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.69 (dd, J = 7.8, 7.3 Hz, 1H), 7.79
(d, J = 8.3 Hz, 2H), 7.83 (d, J = 9.3 Hz, 1H), 7.97 (d, J = 8.3 Hz, 2H), 8.31
(d, J = 7.3 Hz, 1H), 8.64 (d, J = 4.8 Hz, 1H). 13C NMR (CDCl3) δ 82.5,
92.5, 114.7, 114.9, 119.0, 121.9, 121.9, 122.4, 123.6 (q, JCꢀF = 272.1 Hz),
126.0 (q, JCꢀF = 4.4 Hz), 127.0, 128.2, 130.8 (q, JCꢀF = 33.0 Hz), 132.8,
135.7, 136.1, 137.0, 143.6, 150.0. 19F NMR (CDCl3) δ ꢀ63.1. MS (EI)
m/z 363 (M+); HRMS (EI) calcd for C21H12F3N3 (M+) 363.0983,
found 363.0968.
1-(2-Pyridyl)ethynyl-3-(4-methoxyphenyl)imidazo[1,5-a]-
pyridine (4bd). Yellow solid. Mp 166ꢀ167 °C, Rf = 0.10 (n-hexane/
EtOAc = 2:1); IR (KBr) 2975, 2360, 2199, 1608, 1580, 1529, 1509,
1462, 1255, 1182, 1143, 1021, 839, 778, 742 cmꢀ1. 1H NMR (CDCl3)
δ 3.84 (s, 3H), 6.61 (dd, J = 7.3, 6.3 Hz, 1H), 6.86 (dd, J = 9.0, 6.3 Hz,
1H), 7.01 (d, J = 8.8 Hz, 2H), 7.17 (d, J = 7.8, 4.9 Hz, 1H), 7.55 (d, J = 7.3
Hz, 1H), 7.63 (dd, J = 7.8, 7.0 Hz, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.75
(d, J = 9.0 Hz, 1H), 8.17 (d, J = 7.0 Hz, 1H), 8.60 (d, J = 4.9 Hz, 1H). 13C
NMR (CDCl3) δ 55.3, 83.3, 92.3, 113.4, 113.9, 114.3, 118.8, 121.2,
121.6, 122.0, 122.1, 126.8, 129.6, 135.0, 136.0, 138.6, 143.8, 149.7, 160.2.
MS (EI) m/z 325 (M+); HRMS (EI) calcd for C21H15N3O (M+)
325.1215, found 325.1222.
1-(1-Naphthyl)ethynyl-3-(4-trifluoromethylphenyl)imi-
dazo[1,5-a]pyridine (4ce). Yellow solid. Mp 177ꢀ178 °C, Rf = 0.22
(n-hexane/EtOAc = 4:1); IR (KBr) 2359, 2202, 1615, 1505, 1460,
1
1410, 1386, 1326, 1166, 1124, 1068, 957, 852, 799, 744 cmꢀ1. H
NMR (CDCl3) δ 6.69 (dd, J = 7.3, 6.8 Hz, 1H), 6.94 (dd, J = 8.8, 6.8
Hz, 1H), 7.45 (dd, J = 7.8, 7.3 Hz, 1H), 7.52 (dd, J = 8.3, 7.8 Hz, 1H),
7.60 (dd, J = 7.8, 6.8 Hz, 1H), 7.76ꢀ7.78 (m, 2H), 7.77 (d, J = 8.3 Hz,
1H), 7.83 (d, J = 7.8 Hz, 2H), 7.85 (d, J = 7.3 Hz, 1H), 7.96 (d, J = 7.8
Hz, 2H), 8.26 (d, J = 7.3 Hz, 1H), 8.53 (d, J = 8.8 Hz, 1H). 13C NMR
(CDCl3) δ 87.2, 91.2, 114.8, 115.9, 118.9, 121.0, 121.5, 121.8, 123.8
(q, JCꢀF = 271.1 Hz), 125.3, 126.0 (q, JCꢀF = 3.3 Hz), 126.4, 126.4,
126.7, 128.2, 128.3, 128.5, 130.2, 130.7 (q, JCꢀF = 33.1 Hz), 132.9,
133.0, 133.2, 134.9, 136.8. 19F NMR (CDCl3) δ ꢀ63.0. MS (EI) m/z
412 (M+); HRMS (EI) calcd for C26H15F3N2 (M+) 412.1187, found
412.1197.
1-(1-Naphthyl)ethynyl-3-(4-methoxyphenyl)imidazo[1,5-
a]pyridine (4be). Yellow solid. Mp 163ꢀ164 °C, Rf = 0.35 (n-hexane/
EtOAc = 2:1); IR (KBr) 2360, 2199, 1608, 1576, 1558, 1539, 1458,
1353, 1311, 1244, 1171, 1033, 797, 774, 743 cmꢀ1. 1H NMR (CDCl3)
δ 3.87 (s, 3H), 6.64 (dd, J = 7.3, 6.3 Hz, 1H), 6.89 (dd, J = 9.0, 6.3 Hz,
1H), 7.06 (d, J = 8.8 Hz, 2H), 7.47 (dd, J = 8.3, 7.1 Hz, 1H), 7.54 (dd, J =
8.1, 6.8 Hz, 1H), 7.60 (dd, J = 8.3, 6.8 Hz, 1H), 7.75ꢀ7.78 (m, 3H),
7.81ꢀ7.85 (m, 2H), 7.87 (dd, J = 7.3, 6.3 Hz, 1H), 8.20 (d, J = 7.3 Hz,
1H), 8.59 (d, J = 8.3 Hz, 1H). 13C NMR (CDCl3) δ 55.3, 87.8, 90.8,
113.9, 114.4, 114.7 (two carbon atoms were overlapped), 118.8, 120.8,
121.3, 121.9, 122.1, 125.4, 126.4, 126.5, 126.7, 128.2, 129.7, 130.0, 133.0,
133.2, 134.3, 138.6, 160.3. MS (EI) m/z 374 (M+); HRMS (EI) calcd for
C26H18N2O (M+) 374.1419, found 374.1416.
1-(Trimethylsilyl)ethynyl-3-phenylimidazo[1,5-a]pyridine
(4bf). Brown oil. Rf = 0.30 (n-hexane/EtOAc = 4:1); IR (neat) 2957,
2898, 2836, 3243, 1611, 1249, 839 cmꢀ1. 1H NMR (CDCl3) δ ꢀ0.27 (s,
9H), 3.87 (s, 3H), 6.62 (dd, J = 7.3, 6.3 Hz, 1H), 6.85 (dd, J = 9.3, 6.3 Hz,
1H), 7.02 (d, J = 8.3 Hz, 2H), 7.61 (d, J = 9.3 Hz, 1H), 7.70 (d, J = 8.3 Hz,
2H), 8.17 (d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ ꢀ0.01, 55.3, 97.7,
97.8, 113.8, 114.4, 114.5, 118.8, 120.6, 121.9, 122.0, 129.7, 134.6, 138.1,
160.3. MS (EI) m/z 320 (M+); HRMS (EI) calcd for C16H12N2O (M+)
320.1345, found 320.1342.
1-Phenylethynyl-3-(4-trifluoromethylphenyl)imidazo[1,5-a]-
pyridine (4ca). Yellow solid. Mp 157ꢀ159 °C, Rf = 0.40 (n-hexane/
EtOAc = 4:1); IR (KBr) 3087, 2925, 2360, 2206, 1616, 1517, 1486,
1410, 1330, 1172, 1126, 1107, 1070, 856, 758, 745, 692 cmꢀ1. 1H NMR
(CDCl3) δ 6.72 (dd, J = 7.3, 6.3 Hz, 1H), 6.93 (dd, J = 9.3, 6.8 Hz, 1H),
7.33ꢀ7.39 (m, 3H), 7.59 (d, J = 8.3 Hz, 2H), 7.73 (d, J = 9.3 Hz, 1H),
7.77 (d, J = 8.3 Hz, 2H), 7.97 (d, J = 8.3 Hz, 2H), 8.29 (d, J = 7.3 Hz, 1H).
13C NMR (CDCl3) δ 82.1, 92.8, 114.7, 119.0, 121.3, 121.7, 123.3, 123.5
(q, JCꢀF = 272.1 Hz), 126.0 (q, JCꢀF = 3.3 Hz), 128.2, 128.4, 128.6, 130.7
(q, JCꢀF = 33.1 Hz), 130.8, 131.4, 133.0, 134.8, 136.7. 19F NMR
(CDCl3) δ ꢀ63.1. MS (EI) m/z 362 (M+); HRMS (EI) calcd for
C22H13F3N2 (M+) 362.1031, found 362.1035.
1-(4-Methoxyphenyl)ethynyl-3-(4-trifluoromethylphenyl)-
imidazo[1,5-a]pyridine (4cb). Yellow solid. Mp 163ꢀ164 °C, Rf =
0.20 (n-hexane/EtOAc = 2:1); IR (KBr) 2360, 1604, 1519, 1504,
1464, 1411, 1326, 1288, 1250, 1172, 1131, 1106, 1066, 1029, 854
835 cmꢀ1. 1H NMR (CDCl3) δ 3.82 (s, 3H), 6.69 (dd, J = 7.3, 6.3 Hz,
1H), 6.89 (d, J = 8.8 Hz, 2H), 6.90- 6.92 (m, 1H), 7.53 (d, J = 8.8 Hz,
2H), 7.69 (d, J = 9.3 Hz, 1H), 7.76 (d, J = 8.3 Hz, 2H), 7.96 (d, J = 8.3
Hz, 2H), 8.27 (d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ 55.2, 80.7,
1-Phenylethynyl-3-(4-fluorophenyl)imidazo[1,5-a]pyri-
dine (4da). Yellow solid. Mp 157ꢀ159 °C, Rf = 0.40 (n-hexane/
EtOAc = 4:1); IR (KBr) 3560, 2359, 2204, 1633, 1529, 1514, 1351,
1
1313, 1224, 1126, 1065, 1006, 958, 845, 755, 691 cmꢀ1. H NMR
(CDCl3) δ 6.65 (dd, J = 7.3, 6.3 Hz, 1H), 6.88 (dd, J = 8.8, 6.3 Hz, 1H),
7.21 (t, J = 8.8 Hz, 2H), 7.31ꢀ7.37 (m, 3H), 7.60 (d, J = 7.3 Hz, 2H),
7.69 (d, J = 8.8 Hz, 1H), 7.77ꢀ7.80 (m, 2H), 8.27 (d, J = 7.3 Hz, 1H).
13C NMR (CDCl3) δ 82.5, 92.7, 114.2, 114.9, 116.1 (d, JCꢀF = 22.3 Hz),
118.8, 120.8, 121.8, 123.5, 125.7 (d, JCꢀF = 4.1 Hz), 127.9, 128.3, 130.1
(d, JCꢀF = 8.3 Hz), 131.3, 134.3, 137.8, 163.1 (d, JCꢀF = 249.8 Hz). 19
F
NMR (CDCl3) δ ꢀ111.4. MS (EI) m/z 312 (M+); HRMS (EI) calcd for
C21H13FN2 (M+) 312.1063, found 312.1059.
1-(4-Methoxyphenyl)ethynyl-3-(4-fluorophenyl)imidazo-
[1,5-a]pyridine (4db). Yellow solid. Mp 144ꢀ145 °C, Rf = 0.30 (n-
hexane/EtOAc = 2:1); IR (KBr) 3090, 2360, 2202, 1603, 1529, 1283,
1248, 1223, 838, 745 cmꢀ1. 1H NMR (CDCl3) δ 3.82 (s, 3H), 6.64 (dd,
J = 7.8, 6.3 Hz, 1H), 6.66 (dd, J = 8.8, 6.3 Hz, 1H), 6.89 (d, J = 8.8 Hz,
2H), 7.21 (t, J = 8.8 Hz, 2H), 7.53 (d, J = 8.8 Hz, 2H), 7.69 (d, J = 7.8 Hz,
1H), 7.77ꢀ7.80 (m, 2H), 8.18 (d, J = 8.8 Hz, 1H). 13C NMR (CDCl3) δ
55.2, 81.0, 92.5, 114.0, 114.1, 115.3, 115.6, 116.1 (d, JCꢀF = 21.5 Hz),
118.9, 120.5, 121.7, 125.8 (d, JCꢀF = 3.3 Hz), 130.5 (d, JCꢀF = 8.3 Hz),
132.9, 133.9, 137.2, 159.5, 163.0 (d, JCꢀF = 249.8 Hz). 19F NMR δ
ꢀ111.5. MS (EI) m/z 342 (M+); HRMS (EI) calcd for C22H15FN2O
(M+) 342.1168, found 342.1164.
1-(2-Pyridyl)ethynyl-3-(4-fluorophenyl)imidazo[1,5-a]-
pyridine (4dd). Yellow solid. Mp 132ꢀ133 °C, Rf = 0.30 (n-hexane/
EtOAc = 4:1); IR (KBr) 2359, 2342, 2200, 1579, 1524, 1510, 1224, 851,
777, 745 cmꢀ1. 1H NMR (CDCl3) δ 6.70 (dd, J = 7.3, 6.8 Hz, 1H), 6.93
(dd, J = 9.3, 7.3 Hz, 1H), 7.20ꢀ7.25 (m, 3H), 7.59 (d, J = 6.8 Hz, 1H),
7.67 (dd, J = 9.3, 7.8 Hz, 1H), 7.78ꢀ7.82 (m, 3H), 8.21 (d, J = 6.3 Hz,
1H), 8.63 (d, J = 4.9 Hz, 1H). 13C NMR (CDCl3) δ 82.9, 92.4, 113.9,
114.4, 116.2 (d, JCꢀF = 21.5 Hz), 119.0, 121.5, 121.9, 122.3, 125.5 (d,
JCꢀF = 3.3 Hz), 126.9, 130.2 (d, JCꢀF = 8.3 Hz), 135.3, 136.1, 137.7,
143.8, 149.9, 163.2 (d, JCꢀF = 250.6 Hz). 19F NMR (CDCl3) d ꢀ111.2.
MS (EI) m/z 313 (M+); HRMS (EI) calcd for C20H12FN3 (M+)
313.1015, found 313.1014.
92.8, 114.0, 114.7, 115.4, 118.1, 119.0, 121.0, 121.7, 123.8 (q, JCꢀF
=
272.1 Hz), 125.9 (q, JCꢀF = 4.4 Hz), 128.1, 130.5 (q, JCꢀF = 32.6 Hz),
132.9, 133.0, 134.4, 136.4, 159.6. 19F NMR (CDCl3) δ ꢀ63.0. MS
(EI) m/z 392 (M+); HRMS (EI) calcd for C23H15F3N2O (M+)
392.1136, found 392.1130.
1-(2-Pyridyl)ethynyl-3-(4-trifluoromethylphenyl)imidazo-
[1,5-a]pyridine (4cd). Yellow solid. Mp 129ꢀ130 °C, Rf = 0.35
1-(1-Naphthyl)ethynyl-3-(4-fluorophenyl)imidazo[1,5-a]-
pyridine (4de). Yellow solid. Mp 196ꢀ197 °C, Rf = 0.40 (n-hexane/
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ARTICLE
EtOAc = 4:1); IR (KBr) 2359, 2197, 1531, 1515, 1505, 1351, 1311,
1220, 1157, 1009, 956, 846, 813, 776 cmꢀ1. 1H NMR (CDCl3)δ 6.65
(dd, J = 7.8, 6.3 Hz, 1H), 6.90 (dd, J = 9.3, 6.3 Hz, 1H), 7.20ꢀ7.26 (m,
2H), 7.46 (dd, J = 8.3, 7.1 Hz, 1H), 7.52 (dd, J = 8.3, 6.8 Hz, 1H), 7.60
(dd, J = 8.3, 6.8 Hz, 1H), 7.77 (d, J = 9.3 Hz, 1H), 7.80ꢀ7.83 (m, 4H),
7.86 (d, J= 7.8 Hz, 1H), 8.17 (d, J= 7.1 Hz, 1H), 8.56 (d, J=8.3Hz,1H). 13C
NMR (CDCl3) δ 87.5, 90.9, 114.3, 115.1, 116.2 (d, JCꢀF = 21.5 Hz), 118.8,
121.0, 121.2, 125.3, 125.7 (d, JCꢀF = 3.3 Hz), 126.4, 126.4, 126.7, 128.3,
128.4, 128.6, 130.2 (d, JCꢀF = 8.3 Hz), 130.3, 133.0, 133.2, 134.5, 137.5,
163.2 (d, JCꢀF = 249.8 Hz). 19F NMR (CDCl3) d ꢀ111.3. MS (EI)
m/z 362 (M+); HRMS (EI) calcd for C25H15FN2 (M+) 362.1219, found
362.1221.
1-Phenylethynyl-3-(2-pyridyl)imidazo[1,5-a]pyridine (4ea).
Yellow solid. Mp 109ꢀ110 °C, Rf = 0.40 (n-hexane/EtOAc = 4:1); IR
(KBr) 3040, 2360, 2207, 1586, 1562, 1487, 1428, 1356, 1328, 1312, 1275,
1066, 1002, 781, 746, 689 cmꢀ1. 1H NMR (CDCl3) δ 6.78 (dd, J = 7.3, 6.8
Hz, 1H), 7.00 (dd, J = 9.8, 6.8 Hz, 1H), 7.21 (dd, J = 7.3, 4.9 Hz, 1H),
7.32ꢀ7.39 (m, 3H), 7.63 (d, J = 7.8 Hz, 2H), 7.74 (d, J = 9.3 Hz, 1H), 7.77
(d, J=8.1, 7.3Hz, 1H), 8.46(d,J= 8.1 Hz, 1H), 8.61 (d, J=4.9Hz,1H), 9.99
(d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ 82.5, 92.6, 114.3, 115.0, 117.8,
122.0, 122.0, 122.1, 123.4, 126.7, 127.9, 128.2, 131.4, 135.1, 135.5, 136.5,
148.0, 150.3. MS (EI) m/z 295 (M+); HRMS (EI) calcd for C20H13N3
(M+) 295.1109, found 295.1110.
(dd, J = 7.8, 4.9 Hz, 1H), 7.46 (dd, J = 7.8, 7.6 Hz, 1H), 7.52 (dd, J = 7.6,
6.8 Hz, 1H), 7.61 (dd, J = 8.3, 6.8 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H),
7.79ꢀ7.86 (m, 4H), 8.43 (d, J = 8.3 Hz, 1H), 8.57 (d, J = 8.3 Hz, 1H),
8.62 (d, J = 4.9 Hz, 1H), 10.00 (d, J = 7.6 Hz, 1H). 13C NMR (CDCl3) δ
87.5, 90.9, 114.4, 115.2, 117.9, 121.1, 112.2, 122.3, 125.3, 126.3, 126.4,
126.7, 126.8, 128.3, 128.4, 130.2, 133.0, 133.2, 135.3, 135.7, 136.6, 148.2,
150.4. MS (EI) m/z 345 (M+); HRMS (EI) calcd for C24H15N3 (M+)
345.1266, found 345.1263.
1-(4-Fluorophenylethynyl)-3-(2-pyridyl)imidazo[1,5-a]-
pyridine (4ej). Yellow solid. Mp 168ꢀ170 °C, Rf = 0.27 (n-hexane/
EtOAc = 4:1); IR (KBr) 3056, 2208, 1589, 1498, 1428, 1227, 1149 cmꢀ1
.
1H NMR (CDCl3) δ 6.81 (dd, J = 7.3, 6.8 Hz, 1H), 6.99ꢀ7.08 (m, 3H),
7.22 (dd, J = 8.8, 4.9 Hz, 1H), 7.60 (dd, J = 8.8, 5.8 Hz, 2H), 7.73 (d, J =
9.3 Hz, 1H), 7.79 (dd, J = 8.3, 7.3 Hz, 1H), 8.42 (d, J = 8.3 Hz, 1H), 8.64
(d, J = 4.9 Hz, 1H), 10.01 (d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ 82.6,
91.9, 114.4, 114.9, 115.6 (d, JCꢀF = 22.3 Hz), 117.9, 119.5, 122.1, 122.2,
122.2, 126.8, 133.3 (d, JCꢀF = 8.3 Hz), 135.3, 135.6, 136.6, 148.2, 150.4,
163.2 (d, JCꢀF = 250.6 Hz). 19F NMR (CDCl3) δ ꢀ112.5. MS (EI) m/z
313 (M+); HRMS (EI) calcd for C20H12FN3 (M+) 313.1015, found
313.1013.
1-(4-Chlorophenylethynyl)-3-(2-pyridyl)imidazo[1,5-a]-
pyridine (4ek). Yellow solid. Mp 162ꢀ164 °C, Rf = 0.38 (n-hexane/
EtOAc = 4:1); IR (KBr) 3059, 2205, 1588, 1513, 1428, 1090 cmꢀ1. 1H
NMR (CDCl3) δ 6.81 (dd, J = 7.3, 6.3 Hz, 1H), 7.02 (dd, J = 9.0, 6.3 Hz,
1H), 7.22 (dd, J = 7.6, 4.9 Hz, 1H), 7.33 (d, J = 8.5 Hz, 2H), 7.53 (d, J =
8.5 Hz, 2H), 7.72 (d, J = 9.0 Hz, 1H), 7.79 (dd, J = 7.6, 7.3 Hz, 1H), 8.41
(d, J = 7.3 Hz, 1H), 8.53 (d, J = 4.9 Hz, 1H), 10.01 (d, J = 7.3 Hz, 1H).
13C NMR (CDCl3) δ 83.6, 91.6, 114.5, 114.7, 117.8, 122.0, 122.2, 122.3,
126.9, 128.7, 132.6, 133.9, 135.4, 135.7, 136.6, 136.7, 148.1, 150.4. MS
(EI) m/z 329 (M+); HRMS (EI) calcd for C20H12ClN3 (M+) 329.0720,
found 329.0719.
1-(4-Methoxyphenyl)ethynyl-3-(2-pyridyl)imidazo[1,5-a]-
pyridine (4eb). Yellow solid. Mp 161ꢀ163 °C, Rf = 0.25 (n-hexane/
EtOAc = 2:1); IR (KBr) 2359, 2341, 1607, 1587, 1517, 1504, 1427, 1294,
1
1254, 1169, 1067, 1022, 757 cmꢀ1. H NMR (CDCl3) δ 3.83 (s, 3H),
6.79 (dd, J = 8.3, 7.3 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.98 (dd, J = 8.8,
7.3 Hz, 1H), 7.20 (dd, J = 7.8, 5.3 Hz, 1H), 7.56 (d, J = 8.8 Hz, 2H), 7.73
(d, J = 8.8 Hz, 1H), 7.77 (dd, J = 7.8, 7.3 Hz, 1H), 8.42 (d, J = 8.3 Hz,
1H), 8.63 (d, J = 5.3 Hz, 1H), 10.00 (d, J = 7.3 Hz, 1H). 13C NMR
(CDCl3) δ 55.2, 81.0, 92.5, 114.0, 114.3, 115.4, 115.5, 118.0, 121.8,
122.0, 122.2, 126.7, 133.0, 135.0, 135.3, 136.6, 148.1, 150.5, 159.5. MS
(EI) m/z 325 (M+); HRMS (EI) calcd for C21H15N3O (M+) 325.1215,
found 325.1221.
1-(4-Trifluoromethylphenylethynyl)-3-(2-pyridyl)imi-
dazo[1,5-a]pyridine (4ec). Yellow solid. Mp 132ꢀ134 °C, Rf = 0.26
(n-hexane/EtOAc = 4:1); IR (KBr) 2050, 2918, 2200, 1611, 1588, 1502,
1315 cmꢀ1. 1H NMR (CDCl3) δ 6.84 (dd, J = 7.8, 6.8 Hz, 1H), 7.06 (dd,
J = 9.3, 6.8 Hz, 1H), 7.24 (dd, J = 7.8, 5.8 Hz, 1H), 7.62 (d, J = 7.8 Hz,
2H), 7.70 (d, J = 7.8 Hz, 2H), 7.74 (d, J = 9.3 Hz, 1H), 7.80 (dd,
J = 8.3, 7.8 Hz, 1H), 8.42 (d, J = 8.3 Hz, 1H), 8.65 (d, J = 5.8 Hz, 1H),
10.04 (d, J = 7.8 Hz, 1H). 13C NMR (CDCl3) δ 85.3, 91.6, 114.3, 114.5,
117.8, 122.3, 122.4, 122.6, 125.3 (q, JCꢀF = 4.1 Hz), 126.8 (q, JCꢀF = 272.1
Hz), 127.0, 127.3, 129.3 (q, JCꢀF = 32.3 Hz), 131.5, 135.6, 136.1, 136.7,
148.2, 150.3. 19F NMR (CDCl3) d ꢀ63.1. MS (EI) m/z 363 (M+); HRMS
(EI) calcd for C21H12F3N3 (M+) 363.0983, found 363.0971.
1-(2-Pyridyl)ethynyl-3-(2-pyridyl)imidazo[1,5-a]pyridine
(4ed). Yellow solid. Mp 155ꢀ157 °C, Rf = 0.30 (n-hexane/EtOAc =
4:1); IR (KBr) 3047, 2360, 2209, 1581, 1560, 1513, 1467, 1426, 1324,
1314, 1277, 1247, 1187, 1145, 1124, 1005, 960, 781, 689 cmꢀ1. 1H NMR
(CDCl3) δ 6.84 (dd, J = 7.8, 6.8 Hz, 1H), 7.05 (dd, J = 9.3, 6.8 Hz, 1H),
7.21ꢀ7.24 (m, 2H), 7.62 (d, J = 7.8 Hz, 1H), 7.69 (dd, J = 7.8, 7.3 Hz,
1H), 7.79 (dd, J = 9.0, 8.3 Hz, 1H), 7.86 (d, J = 9.3 Hz, 1H), 8.41 (d, J =
7.3 Hz, 1H), 8.62ꢀ8.64 (m, 2H), 10.01 (d, J = 7.3 Hz, 1H). 13C NMR
(CDCl3) δ 83.0, 92.3, 114.5, 118.0, 122.2, 122.3, 122.7, 126.9, 126.9,
132.0, 132.1, 135.3, 136.1, 136.5, 136.6, 143.7, 148.1, 139.9, 150.3. MS
(EI) m/z 296 (M+); HRMS (EI) calcd for C19H12N4 (M+) 296.1062,
found 296.1060.
1-(1-Naphthyl)ethynyl-3-(2-pyridyl)imidazo[1,5-a]pyri-
dine (4ee). Yellow solid. Mp 157ꢀ159 °C, Rf = 0.30 (n-hexane/
EtOAc = 4:1); IR (KBr) 3116, 2359, 2342, 2192, 1584, 1560, 1502,
1427, 1313, 1276, 1187, 1145, 1098, 795, 766 cmꢀ1. 1H NMR (CDCl3)
δ 6.78 (dd, J = 7.3, 6.8 Hz, 1H), 7.01 (dd, J = 9.3, 6.8 Hz, 1H), 7.19
1-(4-Methylphenylethynyl)-3-(2-pyridyl)imidazo[1,5-a]-
pyridine (4el). Yellow solid. Mp 173ꢀ174 °C, Rf = 0.30 (n-hexane/
EtOAc = 4:1); IR (KBr) 2812, 1586, 1516, 1503, 1428, 1249, 1189cmꢀ1
.
1H NMR (CDCl3) δ 2.37 (s, 3H), 6.80 (dd, J = 7.8, 6.8 Hz, 1H), 7.00 (dd,
J = 9.3, 6.8 Hz, 1H), 7.17 (d, J = 8.8 Hz, 2H), 7.23 (dd, J = 7.3, 6.3 Hz,
1H), 7.52 (d, J = 8.3 Hz, 2H), 7.73ꢀ7.80 (m, 2H), 8.43 (d, J = 7.8 Hz,
1H), 8.63 (d, J = 4.9 Hz, 1H), 10.01 (d, J = 7.3 Hz, 1H). 13C NMR
(CDCl3) δ 21.7, 82.1, 93.1, 114.7, 115.7, 118.4, 120.7, 122.2, 122.4,
122.6, 127.1, 129.4, 131.7, 135.5, 135.8, 136.9, 138.5, 148.5, 150.8. MS
(EI) m/z 309 (M+); HRMS (EI) calcd for C21H15N3 (M+) 309.1266,
found 309.1243.
1-(4-N,N0-Dimethylphenylethynyl)-3-(2-pyridyl)-imidazo-
[1,5-a]pyridine (4em). Yellow solid. Mp 185ꢀ186 °C, Rf = 0.12
(n-hexane/EtOAc = 4:1); IR (KBr) 2909, 2200, 1605, 1585, 1536, 1372,
1189 cmꢀ1. 1H NMR (CDCl3) δ 2.98 (s, 6H), 6.68 (d, J = 8.8 Hz, 2H),
6.77 (dd, J = 7.3, 6.8 Hz, 1H), 6.95 (dd, J = 9.8, 6.8 Hz, 1H), 7.20 (dd, J =
7.8, 4.9 Hz, 1H), 7.51 (d, J = 8.8 Hz, 2H), 7.73ꢀ7.79 (m, 2H), 8.43
(d, J = 8.3 Hz, 1H), 8.61 (d, J = 4.9 Hz, 1H), 9.98 (d, J = 7.3 Hz, 1H). 13C
NMR (CDCl3) δ 40.1, 80.0, 93.6, 110.2, 111.8, 114.3, 116.1, 118.1,
121.4, 121.9, 122.1, 126.5, 130.6, 132.7, 134.9, 136.5, 148.1, 150.0, 150.5.
MS (EI) m/z 338 (M+); HRMS (EI) calcd for C22H18N4 (M+) 338.1531,
found 338.1518.
1-(2-Pyridyl)-3-(2-formyl-phenyl)imidazo[1,5-a]pyridine
(4en). Yellow solid. Mp 153ꢀ154 °C, Rf = 0.20 (n-hexane/EtOAc =
4:1); IR (KBr) 2195, 1687, 1590, 1517, 1505, 1268, 1189, 752,
689 cmꢀ1. 1H NMR (CDCl3) δ 6.89 (dd, J = 7.4, 6.8 Hz, 1H), 7.12
(dd, J = 9.3, 6.8 Hz, 1H), 7.27ꢀ7.30 (m, 1H), 7.46 (dd, J = 7.8, 7.3 Hz,
1H), 7.62 (dd, J = 7.8, 7.3 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.78ꢀ7.84
(m, 2H),7.98(d,J=7.8Hz,1H),8.45(d,J=8.3Hz,1H),8.68(d,J=4.8Hz,
1H), 10.09 (d, J = 7.4 Hz, 1H), 10.77 (s, 1H). 13C NMR (CDCl3) δ 88.9,
90.1, 114.7, 117.9, 122.4, 122.5, 123.0, 127.1, 127.8, 128.2, 130.6, 133.2,
133.9, 134.2, 135.4, 136.5, 136.8, 141.5, 148.3, 150.3, 191.2. MS (EI) m/z
6155
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ARTICLE
323 (M+). HRMS (EI) calcd for C21H13N3O (M+) 323.1059, found
323.1056.
(CDCl3) δ 83.4, 91.8, 114.7, 114.8, 118.8, 121.0, 121.9, 122.4, 125.5,
126.6, 127.6, 128.6, 131.4, 132.5, 133.9, 134.5, 135.7. MS (EI) m/z 334
(M+); HRMS (EI) calcd for C19H11ClN2S (M+) 334.0331, found
334.0337.
1-[2-(Methoxy)phenyl]ethynyl]-3-(2-pyridyl)imidazo[1,5-a]-
pyridine (4eo). Yellow solid. Mp 169ꢀ171 °C, Rf = 0.23 (n-hexane/
EtOAc = 4:1); IR (KBr) 3113, 3040, 3002, 2969, 2935, 2207, 1531,
1515, 1250, 746 cmꢀ1. 1H NMR (CDCl3) δ 3.97 (s, 3H), 6.83 (dd, J =
7.3, 6.3 Hz, 1H), 6.92ꢀ6.98 (m, 2H), 7.04 (dd, J = 8.8, 6.3 Hz, 1H),
7.22ꢀ7.27 (m, 1H), 7.32 (dd, J = 8.3, 7.3 Hz, 1H), 7.60 (J = 7.3 Hz, 1H),
7.78ꢀ7.82 (m, 2H), 8.44 (d, J = 8.8 Hz, 1H), 8.65 (d, J = 4.8 Hz, 1H),
10.00 (d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ 55.8, 88.5, 89.2, 110.6,
112.7, 114.5, 115.6, 118.2, 120.5, 121.9, 122.1, 122.2, 126.6, 129.5, 133.2,
135.1, 135.6, 136.6, 148.2, 150.4, 159.9. MS (EI) m/z 325 (M+). HRMS
(EI) calcd for C21H15N3O (M+) 325.1215, found 325.1218.
1-[2-(Methylthio)phenyl]ethynyl]-3-(2-pyridyl)imidazo-
[1,5-a]pyridine (4ep). Yellow solid. Mp 161ꢀ162 °C, Rf = 0.03
(n-hexane/EtOAc = 10:1); IR (KBr) 3077, 1582, 1505, 1429, 1343,
1248, 1016 cmꢀ1. 1H NMR (CDCl3) d 2.53 (s, 3H), 6.79 (t, J = 6.8 Hz,
1H), 7.01 (dd, J = 8.3, 6.8 Hz, 1H), 7.11 (dd, J = 7.8, 7.3 Hz, 1H),
7.17ꢀ7.21 (m, 2H), 7.23ꢀ7.29 (m, 1H), 7.56 (d, J = 7.3 Hz, 1H), 7.76
(dd, J = 9.3, 7.8 Hz, 1H), 7.89 (d, J = 9.3 Hz, 1H), 8.40 (d, J = 8.3 Hz,
1H), 8.61 (d, J = 4.4 Hz, 1H), 9.99 (d, J = 7.3 Hz, 1H). 13C NMR
(CDCl3) δ 15.2, 89.3, 90.2, 114.5, 115.0, 118.3, 121.6, 122.1, 122.2,
122.3, 124.1, 124.3, 126.7, 128.3, 131.9, 135.2, 136.0, 136.5, 140.8, 148.0,
150.3. MS (EI) m/z 341. HRMS (EI) calcd for C21H15N3S (M+)
341.0987, found 341.0977.
1-(4-Methylphenylethynyl)-3-(2-thienyl)imidazo[1,5-a]pyri-
dine (4fl). Yellow solid. Mp 161ꢀ162 °C, Rf = 0.45 (n-hexane/EtOAc
= 3:1); IR (KBr) 2945, 2203, 1652, 1558, 1497, 1306, 1256 cmꢀ1. 1H
NMR (CDCl3) δ 2.36 (s, 3H), 6.70 (dd, J = 6.8, 6.3 Hz, 1H), 6.86 (dd,
J = 8.8, 6.8 Hz, 1H), 7.14ꢀ7.16 (m, 3H), 7.42 (d, J = 4.9 Hz, 1H), 7.49
(d, J = 7.8 Hz, 2H), 7.54 (d, J = 2.4 Hz, 1H), 7.67 (d, J = 8.8 HZ, 1H),
8.31 (d, J = 6.3 Hz, 1H). 13C NMR (CDCl3) δ 21.5, 81.7, 92.8, 114.5,
115.4, 118.7, 120.3, 120.6, 122.2, 125.2, 126.4, 127.6, 129.0, 131.2, 131.5,
132.9, 134.2, 138.1. MS (EI) m/z 314 (M+); HRMS (EI) calcd for
C20H14N2S (M+) 314.0878, found 314.0882.
9,9-Dibutyl-2,7-bis(3-phenylimidazo[1,5-a]pyrid-1-yl)-
ethynyl-9H-fluorene (7). Brown solid. Mp 126ꢀ127.5 °C, Rf = 0.15
(n-hexane/EtOAc = 4:1); IR (KBr) 1601, 1509, 1467, 1352, 1300,
1126 cmꢀ1. 1H NMR (CDCl3) δ 0.61ꢀ0.67 (m, 4H), 0.70 (t, J = 7.3 Hz,
6H), 1.11 (quint, J = 7.3 Hz, 4H), 1.99ꢀ2.03 (m, 4H), 6.65 (dd, J = 7.3,
6.3 Hz, 2H), 6.90 (dd, J = 9.3, 6.3 Hz, 2H), 7.46 (t, J = 7.3 Hz, 2H), 7.53
(t, J = 7.3 Hz, 4H), 7.61 (d, J = 7.3 Hz, 2H), 7.62 (s, 2H), 7.68 (d, J = 7.3
Hz, 2H), 7.77 (d, J = 9.3 Hz, 2H), 7.84 (d, J = 7.3 Hz, 4H), 8.28 (d, J = 7.3
Hz, 2H). 13C NMR (CDCl3) δ 13.7, 22.9, 25.8, 40.1, 55.0, 83.1, 93.8,
114.0, 115.1, 118.9, 119.8, 120.8, 122.0, 122.1, 125.9, 128.2, 129.0, 129.1,
129.5, 130.3, 134.2, 138.4, 140.4, 151.1. MS (EI) m/z 710 (M+); HRMS
(EI) calcd for C51H42N4 (M+) 710.3409, found 710.3410.
1,4-Dioctyl-2,5-bis(3-phenylimidazo[1,5-a]pyrid-1-yl)-
ethynylbenzene (9). Brown solid. Mp 116ꢀ117 °C, Rf = 0.13 (n-
hexane/EtOAc = 4:1); IR (KBr) 1911, 1698, 1349, 1124, 1064 cmꢀ1. 1H
NMR (CDCl3) δ 0.85 (t, J = 6.8 Hz, 6H), 1.20ꢀ1.48 (m, 20H), 1.77
(quint, J = 6.8 Hz, 4H), 2.91 (t, J = 6.8 Hz, 4H), 6.66 (dd, J = 6.8, 6.3 Hz,
2H), 6.90 (dd, J = 9.3, 6.3 Hz, 2H), 7.46 (t, J = 7.8 Hz, 2H), 7.48 (s, 2H),
7.53 (t, J = 7.8 Hz, 4H), 7.68 (d, J = 9.3 Hz, 2H), 7.83 (d, J = 7.8 Hz, 4H),
8.28 (d, J = 6.8 Hz, 2H). 13C NMR (CDCl3) δ 14.0, 22.5, 29.2, 29.48,
29.50, 30.4, 31.8, 34.1, 87.1, 91.9, 114.0, 115.3, 118.7, 120.8, 122.1, 122.4,
128.2, 129.0, 129.1, 129.5, 132.1, 134.4, 138.4, 141.4. MS (EI) m/z 734
(M+); HRMS (EI) calcd for C52H54N4 (M+) 734.4348, found 734.4338.
1-(3-Phenylimidazo[1,5-a]pyrid-1-yl)ethynyl-3-phenyl-
imidazo[1,5-a]pyridine (11a). Brown solid. Mp 188ꢀ190 °C, Rf =
0.49 (n-hexane/EtOAc = 1:1); IR (KBr) 2923, 2364, 1614, 1511, 1322,
1133, 1103, 1063, 695 cmꢀ1. 1H NMR (CDCl3) δ 6.63 (dd, J = 7.3,
6.3 Hz, 1H), 6.69 (t, J = 6.8 Hz, 1H), 6.83ꢀ6.90 (m, 2H), 7.43 (t, J =
7.3 Hz, 1H), 7.51 (dd, J = 7.8, 7.3 Hz, 2H), 7.74ꢀ7.82 (m, 6H), 7.97
(d, J = 8.3 Hz, 2H), 8.24ꢀ8.28 (m, 2H). 13C NMR (CDCl3) δ 85.1,
86.0, 114.1, 114.7, 115.0, 116.1, 119.0, 119.2, 120.8, 121.1, 121.6,
121.9, 123.7 (q, J = 272.1 Hz, CF3), 125.9 (q, J = 3.3 Hz, CF3ꢀCdC),
128.1, 129.0, 129.1, 129.5, 130.0, 130.3 (q, J = 33.1 Hz, CF3-C),
133.1, 134.4, 134.7, 136.4, 138.2 (Ar). 19F NMR (CDCl3) δ ꢀ63.0.
MS (EI) m/z 478 (100, M+). HRMS (EI) calcd for C29H17F3N4 (M+)
478.1405, found 478.1403.
1-{3-(4-Trifluoromethylphenylimidazo[1,5-a]pyridin-1-yl)-
ethynyl-3-(4-methoxyphenyl)imidazo[1,5-a]pyridine (11b).
Brown solid. Mp 198ꢀ200 °C, Rf = 0.13 (n-hexane/EtOAc = 4:1); IR
(KBr) 2922, 1631, 1613, 1530, 1514, 1415, 1351, 1324, 1286, 1246,
1163, 1064, 835 cmꢀ1. 1H NMR (CDCl3) δ 3.87 (s, 3H), 6.62 (dd, J =
7.2, 6.6 Hz, 1H), 6.71 (dd, J = 7.2, 6.6 Hz, 1H), 6.83 (dd, J = 9.1, 6.6 Hz,
1H), 6.88 (dd, J = 9.1, 6.6 Hz, 1H), 7.05 (d, J = 8.8 Hz, 2H), 7.73ꢀ7.82
(m, 6H), 7.96 (d, J = 8.3 Hz, 2H), 8.19 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 7.2
Hz, 1H). 13C NMR (CDCl3) δ 55.3, 85.1, 86.1, 113.9, 114.4, 114.6,
114.7, 119.0, 119.4, 120.5, 121.1, 121.6, 121.9, 122.0, 124.0 (q, J = 272.1
Hz, CF3), 126.0 (q, J = 3.3 Hz, CF3ꢀCdC), 128.3, 129.7, 130.5 (q, J =
33.1 Hz, CF3-C), 133.1, 134.2, 134.8, 135.2, 136.4, 138.3, 160.2. 19F
NMR (CDCl3) dꢀ63.0. MS (EI) m/z 508 (M+). HRMS (EI) calcd for
C30H19F3N4O (M+) 508.1511, found 508.1510.
1-Phenylethynyl-3-(2-thienyl)imidazo[1,5-a]pyridine (4fa).
Yellow solid. Mp 174ꢀ175 °C, Rf = 0.38 (n-hexane/EtOAc = 3:1); IR
(KBr) 2931, 1652, 1558, 1509, 1487, 1249, 1047 cmꢀ1 1H NMR
.
(CDCl3) δ 6.75 (dd, J = 6.8, 6.3 Hz, 1H), 6.91 (dd, J = 8.8, 6.3 Hz,
1H), 7.19 (dd, J = 4.9, 3.4 Hz, 1H), 7.32ꢀ7.38 (m, 3H), 7.45 (d, J = 4.9 Hz,
1H), 7.57ꢀ7.61 (m, 3H), 7.72 (d, J = 8.8 Hz, 1H), 8.36 (d, J = 6.8 Hz,
1H). 13C NMR (CDCl3) δ 82.3, 92.9, 114.6, 115.2, 118.9, 120.8, 122.3,
123.4, 125.4, 126.5, 127.6, 127.9, 128.3, 131.3, 131.4, 133.0, 134.3. MS (EI)
m/z 300 (M+) calcd for C19H12N2S (M+) 300.0721, found 300.0721.
1-(4-Trifluoromethylphenylethynyl)-3-(2-thienyl)imi-
dazo[1,5-a]pyridine (4 fc). Yellow solid. Mp 144ꢀ146 °C, Rf = 0.25
(n-hexane/EtOAc = 4:1); IR (KBr) 3076, 2201, 1635, 1560, 1537, 1227,
1210 cmꢀ1. 1H NMR (CDCl3) δ 6.78 (dd, J = 6.8, 6.3 Hz, 1H), 6.97 (dd,
J = 8.8, 6.8 Hz, 1H), 7.21 (t, J = 4.4 Hz, 1H), 7.48 (d, J = 4.4 Hz, 1H),
7.60ꢀ7.74 (m, 6H), 8.40 (d, J = 6.3 Hz, 1H). 13C NMR (CDCl3) δ 21.5,
85.4, 92.1, 114.8, 115.1, 119.1, 121.7, 122.8, 124.4 (q, J = 272.1 Hz, CF3),
125.6 (q, J = 3.3 Hz, CF3ꢀCdC), 126.0, 127.2, 128.0, 129.8 (q, J = 32.6
Hz, CF3-C), 131.6, 131.7, 133.8, 135.2. 19F NMR (CDCl3) δ ꢀ63.0. MS
(EI) m/z 368 (M+); HRMS (EI) calcd for C20H11F3N2S (M+)
368.0595, found 368.0605.
1-(4-Fluorophenylethynyl)-3-(2-thienyl)imidazo[1,5-a]-
pyridine (4fj). Yellow solid. Mp 144ꢀ146 °C, Rf = 0.25 (n-hexane/
EtOAc = 4:1); IR (KBr) 3071, 2210, 1595, 1498, 1402, 1311, 1249,
1229 cmꢀ1. 1H NMR (CDCl3) δ 6.65 (dd, J = 7.4, 6.3 Hz, 1H), 6.82 (dd,
J = 8.8, 6.3 Hz, 1H), 6.92 (t, J = 8.8 Hz, 2H), 7.10 (dd, J = 5.0, 3.6 Hz,
1H), 7.36 (d, J = 5.0 Hz, 1H), 7.46ꢀ7.49 (m, 3H), 7.60 (d, J = 8.8 Hz,
1H), 8.26 (d, J = 7.4 Hz, 1H). 13C NMR (CDCl3) δ 82.0, 91.7, 114.5,
114.9, 115.6 (d, J = 21.5 Hz, FꢀCdC), 118.7, 119.5 (d, J = 3.3 Hz,
FꢀCdCꢀCdC), 120.8, 122.3, 125.4, 126.5, 127.6, 131.4, 133.1, 133.1
(d, J = 8.3 Hz, FꢀCdCꢀC), 134.3, 162.3 (d, J = 249.8 Hz, F-C). 19
C19H11FN2S (M+) 318.0627, found 318.0621.
F
NMR (CDCl3) d ꢀ111.6. MS (EI) m/z 318 (M+); HRMS (EI) calcd for
1-(4-Chlorophenylethynyl)-3-(2-thienyl)imidazo[1,5-a]-
pyridine (4fk). Yellow solid. Mp 107ꢀ109 °C, Rf = 0.40 (n-hexane/
EtOAc = 3:1); IR (KBr) 2925, 2201, 1652, 1512 m 1487, 1309, 1253,
1089 cmꢀ1. 1H NMR (CDCl3) δ 6.77 (dd, J = 6.8, 6.3 Hz, 1H), 6.94 (dd,
J = 8.8, 6.3 Hz, 1H), 7.20 (dd, J = 4.8, 3.4 Hz, 1H), 7.33 (d, J = 8.8 Hz,
2H), 7.47 (d, J = 4.8 Hz, 1H), 7.52 (d, J = 8.8 Hz, 2H), 7.59 (d, J = 3.4 Hz,
1H), 7.21 (d, J = 8.8 Hz, 1H), 8.40 (d, J = 6.8 Hz, 1H). 13C NMR
6156
dx.doi.org/10.1021/jo200864x |J. Org. Chem. 2011, 76, 6146–6158

The Journal of Organic Chemistry
ARTICLE
Synthesis of 1-Ethynyl-imidazo[1,5-a]pyridines 10. To a
solution of corresponding 4 (0.5 mmol) in THF was added TBAF in THF
(2 equiv), and the mixture was stirred for 1 h at room temperature. The
mixture was diluted with water (5 mL), extracted with DCM (10 mL ꢁ 3),
washed with water and brine, dried over MgSO4, and concentrated in
vacuo. The residue was purified by flash column chromatography on
silica gel (n-hexane/EtOAc) to give the desilylated product 10.
1-Ethynyl-3-phenylimidazo[1,5-a]pyridine (10a). Brown oil.
Rf = 0.35 (n-hexane/EtOAc = 4:1); IR (neat) 3289, 3062, 2102, 1509,
774 cmꢀ1. 1H NMR (CDCl3) δ 3.39 (s, 1H), 6.54 (dd, J = 8.8, 6.6 Hz,
1H), 6.78 (dd, J = 8.3, 6.6 Hz, 1H), 7.34ꢀ7.38 (m, 1H), 7.44 (t, J = 8.1 Hz,
2H), 7.52 (d, J = 8.8 Hz, 1H), 7.71 (d, J = 8.1 Hz, 2H), 8.15 (d, J = 8.3 Hz,
1H). 13C NMR (CDCl3) δ 77.0, 80.4, 113.5, 113.7, 118.0, 120.9, 121.7,
127.8, 128.7, 128.8, 129.1, 134.7, 137.7. MS (EI) m/z 218 (M+); HRMS
(EI) calcd for C15H10N2 (M+) 218.0844, found 218.0842.
1-Ethynyl-3-(4-methoxyphenyl)imidazo[1,5-a]pyridine (10b).
Brown oil. Rf = 0.24 (n-hexane/EtOAc = 4:1); IR (neat) 3292, 3003,
2097, 1611, 1257, 835, 697 cmꢀ1. 1H NMR (CDCl3) δ 3.40 (s, 1H),
3.84 (s, 3H), 6.57 (dd, J = 7.3, 6.3 Hz, 1H), 6.82 (dd, J = 9.1, 6.3 Hz,
1H), 7.00 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 9.1 Hz, 1H), 7.67 (d, J = 8.8
Hz, 2H), 8.15 (d, J = 7.3 Hz, 2H). 13C NMR (CDCl3) δ 55.2, 77.2,
80.4, 113.3, 113.7, 113.8, 118.3, 120.8, 121.8, 122.0, 129.6, 134.7, 138.1,
160.2. MS (EI) m/z 248 (M+). HRMS (EI) calcd for C16H12N2O (M+)
248.0950, found 248.0954.
EtOAc = 10:1); IR (KBr) 3029, 2926, 1635, 1625, 1607, 1572,
1
1325 cmꢀ1. H NMR (CDCl3) δ 6.62 (dd, J = 7.3, 6.3 Hz, 1H),
6.84 (dd, J = 8.8, 6.3 Hz, 1H), 7.25 (t, J = 7.8 Hz, 1H), 7.34 (dd, J = 7.8,
7.3 Hz, 2H), 7.35 (d, J = 16.1 Hz, 1H), 7.54 (d, J = 16.1 Hz, 1H), 7.59
(d, J = 7.3 Hz, 2H), 7.70 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.3 Hz, 2H),
7.98 (d, J = 8.3 Hz, 2H), 8.20 (d, J = 7.3 Hz, 1H). 13C NMR (CDCl3)
δ 114.2, 118.1, 118.3, 119.9, 121.6, 124.0 (q, J = 272.1 Hz, CF3),
126.0 (q, J = 3.3 Hz, C=CꢀCF3), 126.3, 126.8, 127.1, 128.3, 128.3,
128.7, 129.8, 130.5 (q, J = 33.1 Hz, CꢀCF3), 131.3, 133.5, 137.9. 19
for C22H15F3N2 (M+) 364.1187, found 364.1180.
F
NMR (CDCl3) δ ꢀ62.8. MS (EI) m/z 364 (M+). HRMS (EI) calcd
3-(2-Pyridyl)-1-styrylimidazo[1,5-a]pyridine (13ea). Yellow
solid. Mp 168ꢀ170 °C, Rf = 0.20 (n-hexane/EtOAc = 10:1); IR (KBr)
3047, 1621, 1585, 1560, 743 cmꢀ1. 1H NMR (CDCl3) δ 6.56 (dd, J =
7.3, 6.5 Hz, 1H), 6.75 (d, J = 8.8, 6.5 Hz, 1H), 7.03 (dd, J = 7.3, 4.4 Hz,
1H), 7.09 (t, J = 7.3 Hz, 1H), 7.21 (d, J = 16.1 Hz, 1H), 7.22 (d, J = 7.3 Hz,
2H), 7.39 (d, J = 16.1 Hz, 1H), 7.43 (d, 7.3 Hz, 2H), 7.53 (d, J = 8.8 Hz,
1H), 7.63 (dd, J = 7.8, 7.3 Hz, 1H), 8.3 (d, J = 7.8 Hz, 1H), 8.47 (d, J = 4.4
Hz, 1H), 9.77 (d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ 113.9, 117.3,
118.5, 120.8, 121.9, 122.3, 126.3, 126.6, 126.6, 127.0, 128.7, 130.7, 130.7,
135.5, 136.5, 138.0, 148.2, 150.8. MS (EI) m/z 297 (M+); HRMS (EI)
calcd for C20H15N3 (M+) 297.1266, found 297.1266.
’ ASSOCIATED CONTENT
General Procedure for the Heck Reaction of 1. To a screw-
capped test tube was added Cs2CO3 (1.5 equiv). The test tube was dried
at 150 °C in vacuo for 3 h. To the test tube were added Pd(OAc)2 (5 mol
S
Supporting Information. X-ray analyses of 4ea and 4fa,
b
Figures S1ꢀ7, Tables S1ꢀ12, and copies of 1H and 13C NMR for
all new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
%), IPr HCl (10 mol %), 1-iodo-3-arylimidazo[1,5-a]pyridine 1 (0.25
3
mmol), freshly distilled styrene (1.1 equiv), and DMA (1 mL). The
resulting mixture was stirred under an Ar atmosphere at 130 °C for 20 h.
The residue was purified by flash column chromatography on silica gel
(n-hexane/EtOAc) to give the coupling product 13.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: fshiba@gifu-u.ac.jp; mtoshi@gifu-u.ac.jp.
3-Phenyl-1-styrylimidazo[1,5-a]pyridine (13aa). Yellow so-
lid. Mp 114.5ꢀ115.5 °C, Rf = 0.30 (n-hexane/EtOAc = 10:1); IR (KBr)
3025, 1623, 1595, 1299, 737 cmꢀ1. 1H NMR (CDCl3) δ 6.61 (dd, J =
7.3,6.3 Hz, 1H), 6.83 (dd, J = 9.3, 6.3 Hz, 1H), 7.27ꢀ7.32 (m, 1H),
7.40ꢀ7.45 (m, 3H), 7.50ꢀ7.65 (m, 6H), 7.71 (d, J = 9.3 Hz, 1H), 7.89
(d, J = 7.3 Hz, 2H), 8.23 (d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ 113.4,
118.1, 118.4, 119.5, 121.9, 126.2, 126.9, 128.3, 128.5, 128.6, 129.0, 129.1,
129.3, 129.9, 130.5, 138.1, 138.7. MS (EI) m/z 296 (M+); HRMS (EI)
calcd for C21H16N2 (M+) 296.1313, found 296.1312.
’ ACKNOWLEDGMENT
This research was supported by a Grant-in-Aid for Scientific
Research from the MEXT and JSPS.
’ REFERENCES
3-Phenyl-1-{(4-trifluoromethylphenyl)ethenyl}limidazo-
[1,5-a]pyridine (13ac). Yellow solid. Mp 145ꢀ147 °C, Rf = 0.28 (n-
hexane/EtOAc = 10:1); IR (KBr) 3028, 2933, 1617, 1596, 1574,
1322 cmꢀ1. 1H NMR (CDCl3) δ 6.61 (dd, J = 7.3, 6.3 Hz, 1H), 6.84
(dd, J = 9.3, 6.3 Hz, 1H), 7.43ꢀ7.69 (m, 10H), 7.84 (d, J = 7.3 Hz, 2H),
8.21 (d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ 113.4, 117.6, 119.9, 120.3,
121.8, 124.0, 124.1 (q, J = 272.1 Hz, CF3), 125.3 (q, J = 3.3 Hz,
C=CꢀCF3), 125.8, 128.0 (q, J = 33.1 Hz, CꢀCF3), 128.1, 128.8, 128.9,
129.4, 129.6, 129.6, 138.9, 141.3. 19F NMR (CDCl3) δ ꢀ62.8. MS (EI)
m/z 364 (M+); HRMS (EI) calcd for C22H15F3N2 (M+) 364.1187.
Found 364.1189.
3-(4-Methoxyphenyl)-1-styrylimidazo[1,5-a]pyridine (13ba).
Yellow solid. Mp 163ꢀ164 °C, Rf = 0.20 (n-hexane/EtOAc = 10:1); IR
(KBr) 3028, 1623, 1609, 1593, 1254, 733 cmꢀ1. 1H NMR (CDCl3) δ 3.86
(s, 3H), 6.51(dd, J= 7.3, 6.8 Hz, 1H), 6.74 (dd, J= 8.8, 6.8 Hz, 1H), 7.09 (d,
J = 8.8 Hz, 2H), 7.23 (t, J = 7.3 Hz, 1H), 7.34ꢀ7.38 (m, 3H), 7.52 (d, J =
16.1 Hz, 1H), 7.58 (d, J = 7.8 Hz, 2H), 7.63 (d, J = 8.8 Hz, 1H), 7.75 (d, J =
8.8 Hz, 2H), 8.10 (d, J = 7.3 Hz, 1H). 13C NMR (CDCl3) δ 55.3, 113.2,
114.5, 118.1, 118.4, 119.3, 121.8, 122.4, 125.9, 126.1, 126.8, 128.6, 129.0,
129.8, 130.1, 138.2, 138.8, 160.2. MS (EI) m/z 326 (M+);HRMS(EI) calcd
for C22H18N2O (M+) 326.1419, found 326.1418.
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1-Styryl-3-(4-trifluoromethylphenyl)imidazo[1,5-a]pyri-
dine (13ca). Yellow solid. Mp 143ꢀ145 °C, Rf = 0.28 (n-hexane/
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ARTICLE
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(6) For recent advances in the synthesis of imidazo[1,5-a]pyridines
via an acid-mediated condensation pathway, see: (a) Wang, J.; Mason,
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(8) Unpublished results for bis(3-arylimidazo[1,5-a]pyrid-1-yl)sulfides
and methyl 3-arylimidazo[1,5-a]pyridine-1-carboxylates.
(9) Calculations were carried out with the Gaussian 03 package at
the B3LYP/6-31G level. Frisch, M. J. et al. Gaussian 03; Gaussian Inc.:
Wallingford, CT, 2004.
(10) Functional Organic Materials: Synthesis, Strategies, and Applica-
tions; M€uller, T. J. J., Bunz, U. H. F., Eds.; Wiley-VCH: Weinheim, 2007.
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Chinchilla, R.; Nꢀajera, C. Chem. Rev. 2007, 107, 874.
(12) For a recent general review of MizorokiꢀHeck reaction, see:
The MizorokiꢀHeck Reaction; Oestreich, M., Ed.; John Wiley and Sons:
New York, 2009.
(22) X-ray crystallographic analyses of 4ea and 4fa indicated that the
phenyl group on the alkynyl group and imidazo[1,5-a]pyridyl group form
twisted structures in the solid state due to the formation of strong π-stacking
between imidazopyridine rings and the resulting tightly packed crystal
system. See Supporting Information (Figures S3ꢀ6, Table S11).
(23) Carey, F. A.;Sundberg, R. J. InAdvanced Organic Chemistry. Part A:
Structure and Mechanisms, 5th ed.; Springer: New York, 2007; p 339.
(24) Because the calculations only simulate ground-state energy and
localized electronic absorptions and the σ value only correlates ground-
state electron-donor/acceptor properties, fluorescent emission normally
cannot be understood with DFT and/or TD-DFT calculations and the
σ value directly, in particular with the absorption and emission that occur
via charge-transfer (CT)-type transition in excitationꢀrelaxation mechanism.
Meanwhile, it is obvious from Figure 3 that the energy band gaps in
relaxation processes along with fluorescent emission from excited 4 are
strongly correlated to electron-donor/acceptor properties of substituents
and likely to the result of DFT and TD-DFT calculations (i.e., HOMOꢀ
LUMO energy gaps of grand-state orbitals) as well. Also, if the absorp-
tion andemissionoccurwithaCT-typetransitionmechanism, thesespectra
should be changed by polarity of the solvent owing to stabilization of the
excited states, but no recognizable changes of the peak positions were
observed in preliminary solvent-dependent UVꢀvis and fluorescent
studies (in c-hexane, chloroform, acetonitrile, and DMSO) of 4aaꢀac
(Table S12 in Supporting Information) though the shapes slightly
changed in c-hexane (Figure S7 in Supporting Information). The result
probably suggested that at least the relaxation processes along with
fluorescent emission does not occur with CT type transition as a main
factor. At any rate, further investigations are needed to understand the
mechanism.
(25) Mehta, M.; Waldo, P. J.; Larock, C. R. J. Org. Chem. 2009,
(13) For example, see: (a) Berthiol, F.; Feuerstein, M.; Doucet, H.;
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(15) Suffert, J.; Ziessel, R. Tetrahedron Lett. 1991, 32, 757.
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75, 3975.
74, 1141.
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(18) See Supporting Information for full details (Table S9).
(19) See Supporting Information for further details (Table S7).
(20) For selected examples of the correlations between photophy-
sical properties and the Hammett substituent constants, see: (a) Christa,
S. K.; Thomas, J. J. M. Eur. J. Org. Chem. 2003, 18, 3534. (b) Pohl, R.;
Montes, V. A.; Shinar, J.; Anzenbacher, P., Jr J. Org. Chem. 2004,
69, 1723. (c) Yamaguchi, Y.; Tanaka, T.; Kobayashi, S.; Wakamiya, T.;
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C.-C.; Leung, M. J. Org. Chem. 2005, 70, 4323. (e) Potter, G. R.; Hughes,
S. T. J. Org. Chem. 2008, 73, 2995. (f) Zhao, C.-H.; Sakuda, E.; Wakamiya,
A.; Yamaguchi, S. Chem.—Eur. J. 2009, 15, 10603. (g) Ciscato, F. L.;
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75, 6574.
(21) See Supporting Information for details of the photophysical
properties of 3 (Table S10). One of the referees pointed out that
respective linear correlations seem to exist at the positive and negative
regions of σ value on the plot. In fact, as shown in Figure S1, acceptable
approximate lines could be drawn at those regions, respectively, without
the value of 3a. The observation probably suggested that the absorption
and/or emission mechanisms on 3 are totally switched by polarity of
those substituents, and at least it is different from the mechanisms on 4.
Further theoretical and structural investigations are underway to discuss
the correlations.
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dx.doi.org/10.1021/jo200864x |J. Org. Chem. 2011, 76, 6146–6158