Synthesis of 2-Azapyrenes and Their Photophysical and Electrochemical Properties

Article abstract of DOI:10.1021/acs.joc.0c01622

A series of 5,7,9-substituted 2-azapyrenes were synthesized for the first time. The synthesis relies on Br?nsted acid promoted benzannulation of alkyne precursors prepared by palladium-catalyzed cross-coupling reactions. The synthetic strategy is efficient and the scope covers a variety of functional groups. The electrochemical behavior and photophysical properties of the products were investigated by UV-vis and fluorescence spectroscopy, cyclic voltammetry, and DFT calculations.

Full text of DOI:10.1021/acs.joc.0c01622

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Synthesis of 2-Azapyrenes and their
Photophysical and Electrochemical Properties
Ricardo Molenda, Sebastian Boldt, Alexander Villinger, Peter Ehlers, and Peter Langer
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01622 • Publication Date (Web): 04 Sep 2020
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Synthesis of 2-Azapyrenes and their Photophysical
and Electrochemical Properties
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Ricardo Molendaa, Sebastian Boldta, Alexander Villingera, Peter Ehlersa,b, Peter
Langera,b*
a Universität Rostock, Institut für Chemie, A.-Einstein-Str. 3a, 18059 Rostock,
Germany
Tel.: +49 381 498 6410, Fax : +49 381 498 6412, *email: peter.langer@uni-
rostock.de
b Leibniz Institut für Katalyse an der Universität Rostock, A.-Einstein-Str. 29a, 18059
Rostock, Germany
Keywords
Catalysis, cross-coupling, cycloisomerisation, heterocycles, palladium
Graphical abstract
ABSTRACT: A series of 5,7,9-substituted 2-azapyrenes were synthesized for the first time.
The synthesis relies on Brønsted acid promoted benzannulation of alkyne precursors prepared
by palladium-catalyzed cross-coupling reactions. The synthetic strategy is efficient and the
scope covers a variety of functional groups. The electrochemical behavior and photophysical
properties of the products were investigated by UV-Vis and fluorescence spectroscopy, cyclic
voltammetry and DFT calculations.
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Introduction
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In the search for attractive and versatile organic materials, the employment of -conjugated polycyclic
(hetero)aromatic hydrocarbons has become a hot topic in materials science.1,2 In particular, peri-fused
heteroarenes, isostructural or isoelectronic to pyrene, are of high interest, since this 16-conjugated
polycyclic hydrocarbon exhibits unique electronic and photophysical properties. Hence, pyrene has
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become a prominent component in organic electronics3-13 and biomedical chemistry14-21
.
Varying the molecular architecture of the pyrene core by doping with heteroatoms like electronegative
nitrogen into the framework is an effective strategy for tuning the photoelectronic properties. For
example, it has been reported that the incorporation of nitrogen atoms significantly affects the HOMO-
LUMO energy levels, lower the HOMO-LUMO gap and enhances the electron-acceptor ability.27 These
results have intensified the interest in azapyrenes as potential materials for applications in organic
semiconductor devices, such as organic light-emitting diodes (OLEDs), organic field-effect transistors
(OFETs) and organic photovoltaics (OPVs).23-27 Moreover, azapyrenes are promising candidates for
self-assembled molecules28,29, main building units in molecular machines30,31 and DNA intercalators32-
34
.
Synthetic strategies for the construction of azapyrenes have been previously reported based on multi-
step procedures with a set of drawbacks, e.g., harsh conditions, expensive or complex starting
materials, low selectivity and only low functionalization potential.35-37 With regard to 2-azapyrenes
(naphtho[2,1,8-def]isoquinolines), only the unsubstituted parent compound has been reported in the
literature so far. This compound has been prepared by thermal cyclization38, by using a lengthy nine
step-sequence,39 and by PPA (polyphosphoric acid) induced Beckmann rearrangement,40 and by peri-
annulation with sym-triazines41. In the course of the development of Pd-catalyzed cross-coupling
reactions,23,42-50 a number of di- and triazapyrenes and related molecules have been published.25,51-62
.
Recently, the group of Kozaki published an intramolecular Cu(I) catalyzed C–H functionalization
approach,63 while Han et al. applied the classical Bischler-Napieralski cyclization of amide
precursors.27
Despite the importance of aza-analogous pyrenes in the field of materials sciences, many azapyrene
core structures remain essentially unknown, due to the lack of general methods for their synthesis.
Herein, we report what is, to the best of our knowledge, the first synthesis of a series of substituted 2-
azapyrenes. Our synthesis is based on Brønsted acid promoted cycloisomerization of substituted
pyridines which were prepared by regioselective cross-coupling reactions. In addition, we report, for
the first time, a detailed study of the photophysical and electrochemical properties of the products by
UV-Vis and fluorescence spectroscopy, cyclic voltammetry and DFT calculations.
Results and Discussion
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Synthesis
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As starting material, we used 3,5-dibromo-4-chloropyridine 1, which is easily accessible from 4-
pyridone in two steps in 77% overall yield.64 Next, double Sonogashira reactions of pyridine 1 was
studied (for optimization details see SI, Table S1). Finally, the employment of Pd(PPh3)4 (5 mol%), CuI
(5 mol%), diisopropylamine along with 2.2 equiv. alkyne at 50°C in acetonitrile proved to be
appropriate reaction conditions and various 3,5-alkynyl-4-chloro pyridines 2a-h could be prepared in
good to very good yields with high chemoselectivity (Table 1).
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Table 1. Scope of the Sonogashira cross-coupling reaction[a]
R1
R1
R1
Cl
Cl
Br
Br
H
N
N
2a-h
1
Me
Me
Cl
Cl
N
N
2a
2b
(81%)
(87%)
Me
F
F
Cl
Cl
Me
N
N
2c
(80%)
2d
(74%)
CF3
CF3
MeO
OMe
Cl
Cl
N
N
[b]
2e
2f
(75%)
(88%)
Me2N
NMe2
S
S
Cl
Cl
N
N
2g
2h
(80%)
(78%)
[a]
Reaction conditions: 1 (0.37 mmol, 1.0 eq.), Pd(PPh3)4 (5 mol%), CuI (5 mol%), alkyne (2.2 eq.), HNiPr2,
MeCN, 50°C 24h. [b] 2.6 eq. of the alkyne were used.
Subsequent Suzuki reactions (for optimization see SI, Table S2) with para-substituted aryl boronic
acids afforded the key precursors 3a-t in up to 85% yield (Table 2).
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Table 2. Scope of the Suzuki cross-coupling reaction[a]
R2
R2
7
8
9
R1
R1
R1
R1
Cl
B(OH)2
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N
N
3a-t
2a-h
R2
R2
R2
Me
Me
Me
Me
N
N
N
3a R2 = H
75%
85%
3e R2 = H
80%
79%
3i R2 = H
63%
64%
3b R2 = Me
3f R2 = Me
3j R2 = Me
3c R2 = OMe 62%
3g R2 = OMe 64%
3k R2 = OMe 55%
3d R2 = CF3
55%
3h R2 = CF3
55%
R2
R2
R2
F
F
CF3
CF3
S
S
N
N
N
3l R2 = H
74%
78%
3o R2 = H
71%
77%
3r R2 = H
71%
3m R2 = Me
3p R2 = Me
3n R2 = OMe 62%
3q R2 = OMe 57%
R2
R2
MeO
OMe Me2N
NMe2
N
N
3s R2 = H
69%
3t R2 = H
72%
[a]
Reaction conditions: 2a-h (100 mg, 1.0 eq.), arylboronic acid (2.0 eq.), Pd(PPh3)4 (5 mol%), K3PO4 (2.0 eq.),
1,4-dioxane at 90°C for 24h.
With precursors 3a–q in hand, the Brønsted acid mediated benzannulation reaction was studied. The
optimization was carried out with 3b as model compound in the presence of para-toluenesulfonic acid
monohydrate (pTsOH) or methanesulfonic acid (MsOH) at 120°C, respectively (Table 3). These
conditions were previously employed by us for the construction of various N-PAHs.65-67 As summarized
in Table 3, both Brønsted acids performed equally well using a high excess of the employed acid,
providing bis-annulated compound 5b in very good yields in sub-millimolar (entries 2 and 3) and gram-
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scale synthesis (entry 7). Reduction of the amount of pTsOH resulted in exclusive formation of mono-
cyclized isomer 4b, whereas 5b was not formed at all (entry 4). Finally, optimization of the reaction
time gave complete conversion and formation of 4b within 1h at room temperature or, alternatively,
formation of 5b at 120°C for 12h. Thus, we developed two protocols which are suitable for the
selective preparation of mono- and bis-annulated isomers.
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Table 3. Optimization of the Brønsted acid mediated benzannulation reaction[a]
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Brønsted acid
+
N
N
N
5b
3b
4b
Entry
Acid
Solvent
t [h]
T [°C]
Yield 4b [%]
Yield 5b [%]
1
2
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4
5
6
7
-
Xylene
24
24
24
24
12
1
120
120
120
120
120
r.t.
-
-
-
88
-
89
-
86
85
-
86
-
MsOH [60 eq.]
pTsOH [60 eq.]
pTsOH [30 eq.]
MsOH [60 eq.]
MsOH [30 eq.]
MsOH [60 eq.]
-
-
-
-
Xylene
-
12
120
-
87[b]
[a] Reaction conditions for 0.27 mmol (100 mg) of 3b. [b] Reaction conditions for 2.7 mmol (1.0 g) of 3b.
The optimized reaction conditions were applied for the synthesis of various substituted
benzo[f]isoquinolines 4a-k (Table 4) and 2-azapyrenes 5a-o (Table 5). Very good to excellent yields
were obtained for mono-annulated benzo[f]isoquinolines and moderate to excellent yields for bis-
annulated 2-azapyrenes, respectively. Various functional groups were tolerated which did not impact
the yields. A notable decrease in yield was observed for arylalkynes bearing methyl groups in meta-
position which might be explained by steric effects. More significantly, distinct electronic effects on the
yields were observed for the benzannulation during the course of our studies. The strongly electron-
withdrawing trifluoromethyl group located at the arylpyridyl moiety of 3d and 3g resulted in rapid
conversion to give the mono-annulated isomers 4c and 4f in 10 and 5 minutes, respectively. On the
other hand, the cyclization completely failed at room temperature in case of 3o and 3p, where also
CF3-substituents are located at the arylalkynyl moiety. However, efficient annulation of these electron-
deficient alkynes proved to be possible when the reaction was performed at elevated temperatures
(80°C). Thereby the corresponding mono-annulated products 4i and 4j could be obtained within 2h in
very good yields.
In contrast, employment of our double annulation procedure for CF3-containing derivatives 3o, 3p and
3q resulted in rapid decomposition of the starting material, most likely due to less stabilization of
positively charged intermediates during the reaction. Decomposition was also observed for derivative
3s, containing the strongly electron-donating methoxy group, and for 3r bearing a thiophene system.
Fortunately, a switch from MsOH to pTsOH smoothly delivered the desired thiophene-substituted 2-
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azapyrene 5o in very good yield. In comparison, the reactions of 3o and 3p with pTsOH resulted in
formation of mono-annulated products accompanied by traces of the double annulated derivatives,
even after prolonged reaction time of 48h.
7
8
9
Further changes of the temperature and type of acid as well as the addition of various solvents proved
to be not successful. However, twofold annulation of highly reactive 3s was possible by using less
acidic trifluoroacetic acid (TFA) and employing a lower reaction temperature of 60°C. Using these
conditions, it was possible to isolate p-methoxyphenyl-substituted 2-azapyrene 5m, albeit, in only 20%
yield. Reduction to 30 eq. of acid or performing the reaction at room temperature resulted in a drop of
yield to 10%. Finally, we have found, that the use of 3 eq. of TfOH (trifluoromethanesulfonic acid) in
CH2Cl2 at 0°C and 20 °C provided product 5m in 66% yield.
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The presence of substituents located at the aryl moiety (attached to the pyridine) have a less
pronounced impact on the reaction outcome. Accordingly, CF3 containing products 5d and 5i were
obtained in good yield, however, an increased reaction time of 24 h was necessary. Employment of
starting material 3n, containing a methoxy group, resulted in formation of product 5l, albeit, in only
35% yield. This product contains a free hydroxyl group, due to acid induced ether cleavage during the
reaction. However, lowering the amount of acid to 30 eq. of MsOH gave the bis-annulated methoxy
derivative 5c in a yield of 33%. Employment of the highly boiling fluorinated alcohol octafluoropentanol
(OFPO) gave 5c at 120°C using 15 eq. of MsOH. However, formation of the corresponding hydroxy-
derivative could not be suppressed completely which, thus, resulted in only a slightly improved yield
(40%).
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Table 4. Synthesized benzo[f]isoquinolines
4
5
6
CF3
Me
7
8
9
10
11
12
13
14
15
16
17
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19
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22
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N
4c
N
N
[a]
[b]
[c]
4a
4b
(87%)
(94%)
(94%)
(89%)
(93%)
(91%)
(79%)
(96%)
Me
CF3
Me
Me
Me
Me
Me
Me
N
N
N
4d
4e
4f
(92%)
Me
F
CF3
F
F
CF3
F
N
N
N
4g
4h
4i
(86%)
Me
CF3
CF3
S
S
N
4j
N
[c]
4k
(89%)
[a] 10 min reaction time. [b] 5 min reaction time. [c] 2h reaction time at 80°C.
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Table 5. Synthesized 2-azapyrenes
4
5
6
OMe
Me
7
8
9
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11
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N
N
5c
N
[a]
5a (
93)%
5b
(40%)
(86%)
CF3
Me
Me
Me
Me
Me
Me
N
N
N
5f
[b]
5d
5e
(63%)
CF3
(75%)
(78%)
Me
Me
Me
Me
Me
Me
N
N
N
[b]
5h
5i
5g
(82%)
(75%)
(80%)
OH
Me
F
F
F
F
F
F
N
N
N
5j
5k
(79%)
(80%)
5l
(35%)
Me2N
NMe2
MeO
OMe
S
S
N
5n
N
N
[d]
[c]
5o
5m
(86%)
(66%)
(75%)
[a] Reaction carried out with 15 eq. MsOH in OFPO. [b] 24h reaction time. [c] Reaction carried out with 3 eq. TfOH in
CH2Cl2. [d] Reaction carried out with 60 eq. pTsOH.
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The structures of 4j and 5b were independently confirmed by X-ray crystal structure analysis. For
crystal structures and crystallographic data see supporting information. According to the structure
analysis of compound 5b, the phenyl rings are twisted out of plane from the planar core structure with
dihedral angles of 51° and 48°.
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Physical properties
To gain insights into the photophysical properties, steady state absorption and photoluminescence
spectra (PL) for selected 2-azapyrenes were recorded. The key optical data are summarized in Table
6. As depicted in Figure 1, the absorption and emission spectra (except for 5n) are characterized by
well-resolved bands with vibrational progression, highlighting the maintained pyrene-like nature of
transitions in the 2-azapyrene, in which the weak Lb band of the transition dipole forbidden S1 ← S0
electronic excitation in pyrene, represented by the configuration interaction of HOMO-1 → LUMO and
HOMO → LUMO+1 (vide infra), significantly increases upon the incorporation of nitrogen.68,77 In line
with symmetrical 4,10-substituted phenyl70 and –pyridyl71 analogues of pyrene, functionalized aryl
groups located at the 5,9-position on the 2-azapyrene core have only a small effect on the absorption
and emission properties, thus, showing similar overall spectral features. This can be explained by their
poor conjugation of the phenyl groups with the 2-azapyrene core because of their twisted orientation.
Figure 1. UV-Vis (left) and emission (right, ex = 350 nm) spectra of 5,9-diaryl-2-azapyrenes in CH2Cl2 (c = 10-5 M)
at 20°C. Absorption band names are given according to the Platt nomenclature.72
However, strong -donor substituents located at the phenyl groups, like in case of 5m, show a
tendency of band broadening which becomes most prominent for the NMe2-containing product 5n.
The latter compound exhibits a blue-shifted strongly allowed Bb band ( = 50244 M-1 cm-1), followed by
a bathochromically shifted broad absorption with loss of fine structure covering the La and Lb band
regions. Those are indicative of an extensive conjugation over the whole molecule, and the large
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broad unstructured red-shifted emission in the PL spectrum (em,max = 499 nm) emphasizes an
intramolecular charge-transfer (ICT) transition, which has been previously reported for amino
substituted pyrenes.73-76 Comparable emission spectra in CH2Cl2 were also observed for alkyl-
substituted 4,10-diazapyrenes upon protonation of the nitrogen atoms. In these cases the intensity of
the structured initial spectrum decreases with increasing amount of acid and is finally replaced by a
new broad red-shifted emission spectrum which results from an enhanced charge transfer transition.27
In contrast, such a pronounced acid response is not observed for alkyl-substituted 2,7-diazapyrenes
where the nitrogen atoms are doped at the nodal plane positions.26 This highlights the number and
position-property relation of nitrogen doping on the photophysical properties beside the substituent
position effect at the core structure. This also agrees with the different results between our system and
the symmetrical 5,9-p-tolyl-substituted di- and tri-azapyrenes63 investigated by Kozaki and co-workers.
The latter compounds are characterized by bathochromically shifted broad absorption and emission
spectra, suggesting increased conjugation and charge transfer properties. This is supported by their
solvatomchromic and theoretical studies and is most evident for their tetra-azazpyrene derivative
which furthermore implies extensive conjugation of aryl groups at position 2 and/or 7 by adjacent
doping of nitrogen atoms.
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Figure 2. UV-Vis (left) and Emission (right, ex = 350 nm) spectra of 7-substituted-5,9-diphenyl-2-azapyrenes in
CH2Cl2 (c = 10-5 M) at 20°C.
In 2-azapyrene, additional functionalization of the nodal plane position 7 shows only a weak effect,
which is, however, more significant as compared to the 5,9-substituted derivatives (Figure 2 and
Figure S3). The higher lying Bb / Ba as well as the Lb band of the S1 ← S0 transition are influenced by
the substituent in a reverse manner from higher to lower transitions with increasing electron donating
character of the functional groups. In contrast, the La band of the S2 ← S0 transition is insignificantly
influenced by the substituents, consistent with observations for 2- and 2,7-substituted pyrenes.69,71,77
Taking the highest peak into account, both -acceptor and -donor show a notable bathochromic shift
in their emission from 5a by 10 and 21 nm, respectively, whereby the emission of 5c is characterized
by band broadening with loss of vibrational progression. In the overall comparison to parent 2-
azapyrene (em = 374 nm)78 all investigated compounds show a bathochromic shift in their emission
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maxima ranging from 11 to 125 nm and a minor 5 nm when 5a is compared with 4,10-diphenylpyrene
(em = 380 nm).70
6
7
8
9
The 2-azapyrene derivatives show intense fluorescence at 10-5 M concentrations in the blue region of
the spectra, except for compound 5n which exhibits blue-greenish emission in CH2Cl2. The quantum
yields in dichloromethane range from 0.08 to 0.38 and are generally higher for 5,9-substituted 2-
azapyenes, indicating a position and substituent depending quenching effect (Table 6).
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Table 6. Spectroscopic data of selected 2-azapyrenes in dichloromethane (c = 10-5 M) at 20°C.
5a
5b
5c
5d
5g
5j
5m
5n
5o
228
4.52
246
4.53
280
4.36
332
4.24
346
4.34
382
3.75
230
4.51
252
4.64
288
4.43
333
4.28
348
4.39
381
3.63
229
4.48
264
4.69
302
4.45
335
4.25
350
4.34
229
4.42
243
229
4.52
245
4.40
280
4.23
333
4.13
347
4.22
383
3.65
228
4.56
245
4.60
280
4.44
331
4.30
345
4.40
381
3.81
234
4.67
278
4.29
306
4.13
332
4.17
348
4.25
383
3.69
240
4,70
271
4,70
317
4.36
361
4.39
229
4.55
245
4.45
279
4.27
334
4.17
348
4.26
383
3.62

1,abs [nm]
log 1
2,abs [nm]
log 2
3,abs [nm]
log 3
4,abs [nm]
log 4
5,abs [nm]
log 5
6,abs [nm]
log 6
7,abs [nm]

4.43
274

4.21
331

4.10
345

4.20
369

3.60
389

3.75
395
log 7
389[b]
406
426[b]
387
407
428[b]
385
406
429[b]
389
410
434[b]
499
388
408
432[b]
1,em350 [nm]
2,em350 [nm]
3,em350 [nm]
[a]
385
406
427[b]
385
405
427[b]
417
440[b]
0.34
0.31
0.08
0.23
0.38
0.31
0.36
0.33
0.15
[a] Fluorescence standard: quinine hemi sulfate salt monohydrate in 0.05 M H2SO4 ( = 0.52).79 [b] Indicates
shoulder.
To investigate the nature of transitions from the ground to excited states, solvatochromic studies were
performed for 5b and 5n. As shown in Figure 3, the spectral features of 5b are only weakly affected by
the solvent polarity, indicating a strong stabilization of the ground state and a low dipole moment in the
excited state, which is consistent with a π→π* transition without ICT character. Furthermore, no
obvious hydrogen-bonding effects in ethanol were detected. In contrast, the small solvatochromism in
the absorption spectra of 5n and the pronounced blue shift of 87 nm in the emission spectra with
decreasing polarity from dichloromethane (em = 499 nm) to cyclohexane (em = 412 nm) indicates a
highly polarized excited state with a large dipole moment, which further supports ICT characteristic
during excitation. As apparent from the simulated spectra of 5n, the general trends observed in the
experimental absorption spectrum are somewhat reproduced even though the predicted spectrum is
generally underestimated particularly in the lowest absorption area. However, the max of the lowest
absorption band falls into the intersection point of the experimental absorption and emission spectra,
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thus the predicted S1 vertical excitation energy is in accord to the experimentally determined optical
gap value (Table 7). On the other hand, the calculated emission wavelength of 496 nm very well
reproduces the experimental value of 499 nm (Table 6 and Table S24).
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Figure 3. UV-Vis (solid lines) and emission (dashed lines, ex = 350 nm) spectra of 5b (left) and 5n (right)
(c = 10-5 M) at 20°C. Picture (middle): Emission color of 5n in cyclohexane (left) and CH2Cl2 (right) solution
subjected to ultraviolet (UV) irradiation at 366 nm. Normalized absorption and emission spectra of 5n simulated at
the B3LYP/6-31+G(p) level of theory within IEFPCM of dichloromethane, Half-Width at Half Height = 1200 cm-1.
Next, the electrochemical properties of 5a and 5n were characterized by cyclic voltammetry (CV) in
terms of their oxidation behavior (Figure 4). The voltammogram of compound 5a shows two distinct
oxidation peaks, while the CV of 5n displays two broad oxidation events. Furthermore, 5a shows three
oxidation potentials in acetonitrile (Figure S1). The CV scans of both compounds exhibit irreversible
oxidation waves, which was also observed for diazapyrenes.27 The first oxidation onset potential of 5n
(0.26 V vs. Fc/Fc+) is three times lower than that of 5a (0.82 V vs. Fc/Fc+), reflecting an easier
oxidation by installing strong donor N,N-dimethylaniline units. Both voltammograms consist of a small
reduction peak for 5a (-1.28 V vs. Fc/Fc+) and for 5n (-1.23 V vs. Fc/Fc+). Assuming that the HOMO
level of ferrocene80 is 4.80 eV below the vacuum level, the calculated HOMO-LUMO values (Table 7)
of 5a and 5n show close LUMO levels, but a much higher HOMO level for 5n. Hence, a smaller
HOMO-LUMO gap is estimated for 5n (3.39 eV) as compared to 5a (3.83 eV).
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Figure 4. Cyclic voltammograms of 5a (left) and 5n (right) measured in CH2Cl2 with 0.1 M n-Bu4NPF6 as a
supporting electrolyte, glassy carbon working electrode, ANE2 as reference electrode and Pt counter-electrode
with ferrocene as standard at a scan rate of 100 mV s–1.
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9
To get deeper insight into the electronic structures and transition characters, density functional theory
(DFT) and time-dependent DFT (TD-DFT) calculations were carried out. Calculations were performed
with Gaussian0981 using the B3LYP and CAM-B3LYP functionals in combination with the 6-31G(p)
basis set and a polarizable continuum model (PCM) of dichloromethane using the integral equation
formalism variant (IEFPCM) to include solvent effects.
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Figure 5. Calculated frontier molecular orbitals and energy levels at the B3LYP/6-31G(p) level of theory within
IEFPCM of dichloromethane (isovalue = 0.02 a.u.).
As visualized in Figure 5, the HOMO and LUMO of 5a are mainly located on the 2-azapyrene frame,
while the LUMO of 5n primarily resides on the core structure and the HOMO is distributed over the
outside edges of the 2-azapyrene skeleton with a large proportion on the N,N-dimethylaniline units,
which is similarly predicted for methoxy-containing 5m (Figure S4). The calculated HOMO and LUMO
energy levels of 5a and 5n are in very good agreement with the CV data confirming the experimental
results (Table 7). Compared to the parent 2-azapyrene, compound 5a shows only slightly higher
HOMO and lower LUMO levels, but significantly lower HOMO and LUMO levels as compared to
pyrene and 4,10-diphenylpyrene. This exemplifies that the incorporation of nitrogen in position 2
significantly stabilizes both the HOMO and LUMO levels in pyrene, although to less extent than
multiple doped azapyrenes.42,63 Strong -donor groups on the phenyl fragments located at the 5,9-
position significantly lower the HOMO-LUMO gap. Additional terminal groups at position 7 located at
the 2-azapyrene core have only a minor effect on the frontier orbitals and, thus, on the HOMO-LUMO
energy gap, due to the nodal plane stated before (Figure S4 and Figure S5). However, as compared
to 5a, bearing in mind that the S1 ← S0 transition involves HOMO-1 → LUMO and HOMO → LUMO+1,
the non-zero contributed HOMO-1 and LUMO+1 levels of donor OMe-substituted 5c are destabilized
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by 0.38 and 0.15 eV, respectively raising the HOMO-1 orbital energy above that of 5a, whereas the
HOMO and LUMO energy levels remain unaffected. On the other hand, the LUMO+1 and LUMO
levels of acceptor CF3-substituted 2-azapyrene 5d are stabilized by 0.34 and 0.17 eV respectively,
consequently switching the energetic order of these two orbitals with that of 5a, which is consistent
with the observed trend in the experimental absorption and emission spectra.
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The first excited state S1 (Lb) of pyrene is a result of a strongly coupling configuration interaction of
HOMO-1 → LUMO and HOMO → LUMO+1 processing the same symmetry, so that the S1 state is
one of the mixed states with symmetric linear combination which in turn lower the energy in this state
compared to the state involving HOMO → LUMO excitation S2 (La).82,83 Similar situation arise in lower
symmetry (C2v) classified 2-azapyrene68,84 (Pyrene: D2h symmetry), which is specified by the obtained
TD-DFT results. In accordance to pyrene, the order of excited states in 2-azapyrene is more
accurately predicted using the range-separated CAM-B3LYP functional rather than B3LYP.69 Hence,
the S1 ← S0 transition with a low oscillator strength (f = 0.0250) derived from HOMO-1 → LUMO and
HOMO → LUMO+1 with a dominant proportion of the latter. This, thus, differs from the equal mix in
pyrene, while the S2 ← S0 excitation with a high oscillator strength (f = 0.3504) is derived from
HOMO → LUMO with some admixture of HOMO-1 → LUMO+1 (Table S5). Both S1 ← S0 and S2 ← S0
transitions predicted to be strongly influenced by the substitution pattern at the 5,9 and 7-position.
Electron withdrawing groups located at the phenyl groups or directly attached at the 7-position of the
2-azapyrene core retain the order of excited states, while donor groups reverse the order. Their lowest
energy excitations with a high oscillator strength in both B3YLP and CAM-B3YLP mainly derive from
HOMO → LUMO, while the weak S2 ← S0 transitions originate from the configuration interaction of
HOMO-1 → LUMO and HOMO → LUMO+1. In contrast, the first excitation of 5n using the B3LYP
functional is described by a pure HOMO-1 → LUMO transition and the S2 ← S0 transition primarily
arises from HOMO → LUMO. For CAM-B3LYP, the order of the first and second excited states of 5n
is reversed (Table S20 and S21). Thus, the B3LYP functional provides a better overall agreement with
the experimental data of the investigated compounds, but a more accurate ordering of excited states is
obtained using the CAM-B3LYP functional. Consequently, the S1 ← S0 transition of 5n is dominated by
HOMO → LUMO in order that the S1 state of 5n is featured by efficient ICT from the N,N-
dimethylaniline side groups to the 2-azapyrene moiety, supported by the DFT calculated dipole
moments for the S0 ground-state µgs = 6.90 D and S1 excited-state µes = 25.78 D. These results
explain the observed variation in the absorption and emission spectra and verify that the represented
spectral red shift of 5n is derived from the conversion of π→π* to ICT transitions.
Table 7. Optical, electrochemical and theoretical data for compounds 5a and 5n.
UV/Vis - Fluorescence Cyclic Voltammetry
DFT
TD-DFT
(B3LYP)
opt.
Structure
Eg
HOMOcv
[eV]b
LUMOcv
[eV]c
HOMO
[eV]d
LUMO
[eV]d
E [eV]e
[eV]a
5a
5n
3.30
2.92
-5.62
-5.09
-1.79
-1.70
-5.56
-5.03
-1.84
-1.70
3.46 (0.3886)
2.92 (0.1420)
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[a]
[b]
Estimated from the intersection of normalized absorption and emission spectra.
Calculated using the
4
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6
onset
[c]
opt
equation: E(HOMO) = -e[EOx
.
vs. Fc/Fc+)+4.80].
Estimated using correction factor: E(LUMO) = 1.16Eg
-
E(HOMO)cv.85
Calculated DFT energy levels at the B3LYP/6-31G(p) level of theory within IEFPCM.
[d]
[e]
Calculated TD-DFT excitation energies (E) at the B3LYP/6-31+G(p) level of theory within IEFPCM (considering
the reverse order of excited states), oscillator strength (f) in parenthesis.
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Finally, nucleus independent chemical shift (NICS) as a magnetic criteria of aromaticity86,87 were
performed on B3LYP/6-31G(p) optimized gas phase structures at the GIAO-B3LYP/6-311+G(p) level
of theory. The NICS,zz values were obtained employing the -only model88 and the respective NICS-
XY-scans89,90 are presented in Figure 6.
Figure 6. NICS-XY-scans. X-Scans (left). Y-Scans (right). Black letters indicate atoms and center of bonds. Red
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and blue capital letters indicate center of rings. Blue dashed arrow – X-scan trajectory direction. Red dashed
4
5
arrow – Y-scan trajectory direction. All scans were performed at a height of 1.7 Å.
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9
As discussed in detail by Gershoni-Poranne and Stanger88, pyrene can be characterized by a global
ring current enclosing the naphthalene and biphenyl unit, and two local diatropic ring currents within
the respective A rings. The resulting current density is inhomogeneous at the perimeter in such,
increased density arise across the edges of the A rings, were the local currents sum up to the global
component. Aza replacement decreases the local current in the A’ ring, which result in a small effect
on the global component but induce insignificant alterations on the local benzenic current in the
opposite A ring. Substituents in 5,9 position have a negligible effect on the overall tropicity picture
compared to 2-azapyrene, whereas CF3-acceptor and OMe-donor groups in position 7 at the 2-
azapyrene core significantly decrease the currents in both local and global components with a greater
strength in the A’ ring of the pyridine unit and the minimum of the induced magnetic field, which is
centrally located at the long axis in pyrene (maximum in the X-scan trajectory direction), is shifted
from the geometric center.
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Conclusion
In summary, a Brønsted acid mediated benzannulation was developed and used to produce a series
of hithero unreported 2-azapyrenes and benzo[f]isoquinolines in up to excellent yields. Theoretical and
experimental investigations verify, that the incorporation of nitrogen in position 2 significantly stabilizes
both the HOMO and LUMO levels of pyrene, whereby the terminal functional groups and their
respective position at the 2-azapyrene framework play a crucial role for the modulation of the
photophysical and electrochemical properties, and thus for adjusting the HOMO-LUMO gap.
Introduction of strong donor N,N,-dimethylaniline side groups in 5,9 position lead to tunable emission
from blue to blue-greenish color which is attributed to the conversion of π→π* to ICT transitions, as
validated by solvatochromism and DFT/TD-DFT studies. Furthermore, in comparison to 4,10-
diazapyrene ( = 0.11), 1,4,10-triazapyrene ( = 0.092) and 2,4,10-triazapyrene ( = 0.12), bearing the
same terminal groups in 5,9 position,63 2-azapyrene 5g shows an up to four times higher quantum
yield ( = 0.38). These results provide new information about the effect of functionalized nitrogen
doped pyrenes.
EXPERIMENTAL SECTION
General Information
The nuclear magnetic resonance spectra (1H/13C/19F NMR) were recorded on a Bruker AVANCE 300
III, 250 II or 500. The analyzed chemical shifts δ are referenced to residual solvents signals of the
deuterated solvents CDCl3 (δ = 7.26 ppm/77.0 ppm), or TFA-d (δ = 11.50 ppm/164.2 ppm).
Multiplicities due to spin-spin correlation are reported as follows: s = singlet, d = doublet, dd = double
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doublet, t = triplet, pt = pseudo triplet, m = multiplet and further described through their coupling
constants J. Infrared spectra (IR) were measured as attenuated total reflection (ATR) experiments with
a Nicolet 380 FT-IR spectrometer. The signals have been characterized through their wave numbers ṽ
and their corresponding absorption as very strong (vs), strong (s), medium (m), weak (w) or very weak
(vw). UV/VIS spectra were recorded on a Cary 60 UV-VIS spectrophotometer and emission spectra
with an Agilent Cary Eclipse Fluorescence spectrophotometer. Cyclovoltammetry (CV) was measured
in CH2Cl2 and MeCN with 0.1M Bu4NPF6 as supporting electrolyte, glassy carbon working electrode,
ANE2 (Ag/AgNO3 0.01M in MeCN) as reference electrode and Pt counter electrode with ferrocene as
external standard (1 mM in MeCN). The potential is given vs. Fc/Fc+. The potentiostat used was an
AMETEK PARSTAT 4000. Basic and high resolution mass spectra (MS/HRMS) were measured on
instruments which are paired with a preceding gas chromatograph (GC) or liquid chromatograph (LC).
The samples have been ionized through electron impact ionization (EI) on an Agilent 6890/5973 or
Agilent 7890/5977 GC-MS equipped with a HP-5 capillary column using helium carrier gas or by
applying electron spray ionization (ESI) on an Agilent 1200/6210 Time-of-Flight (TOF) LC-MS. Melting
points (mp) were determined by a Micro-Hot-Stage GalenTM III Cambridge Instruments and are not
corrected.
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Materials
The applied solvents Acetonitrile, 1,4-Dioxane, Xylene and Dichloromethane were obtained as dry
solvents through commercial sources and employed without further purification. Solvents for extraction
and column chromatography were available after previous distillation. Other reagents, catalysts,
ligands, acids and bases have been utilized in purchased purity. Column chromatography was
performed using Merck Silica gel 60 (particle size 63–200 µm).
3,5-dibromo-4-chloropyridine (1)
A mixture of Pyridin-4(1H)-one (5.14 g, 54 mmol) and KOH (6.08 g, 108 mmol) dissolved in 100 ml
distilled water was cooled to 0 °C. Then, bromine (17.3 g, 108 mmol) was added dropwise and the
resulting mixture was stirred for 30 min., filtered, washed with distilled water and dried in vacuo. The
residue was dissolved in 50 ml POCl3 (82.92 g, 54 mmol) and stirred under reflux (oil bath) for 12h.
The yellow solution was quenched with ice, neutralized with K2CO3 and extracted with
dichloromethane (3 times). The organic phase was dried over Na2SO4, concentrated in vacuo and
purified by column chromatography (hepatan/EtOAc = 10/1) to obtain 1 as a colorless solid (11.23 g,
1
77%). H NMR (300 MHz, CDCl3) δ 8.65 (s, 2H, CH). 13C{1H} NMR (75 MHz, CDCl3) δ 150.8 (CH),
144.1 (C), 121.8 (C).
General procedure (A) for the synthesis of 3,5-bis(alkynyl)-4-chloropyridines (2a-h)
A pressure tube charged with 100 mg 1 (1 eq., 0.37 mmol), CuI (0.05 eq., 3.5 mg) and Pd(PPh3)4
(0.05 eq., 21.3 mg) was evacuated and backfilled with argon for 3 times. Then, degased
diisopropylamine (1 ml) and dry acetonitrile (2 ml) were added followed by 2.2 eq. (2.6 eq. for 2f) of
the respective alkyne (alkynes that were solids at room temperature were added with 1, CuI and
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catalyst). The pressure tube was sealed with a teflon cap and stirred in a stainless steel heating block
at 50 °C for 24h. After cooling to room temperature, the reaction mixture was quenched with distilled
water and extracted with ethyl acetate (3 times). The organic phase was dried over Na2SO4,
concentrated in vacuo and purified by column chromatography (heptane/ethyl acetate) to obtain the
desired alkynylated products 2a-h.
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General procedure (B) for the synthesis of 4-aryl-3,5-bis(alkynyl)pyridines (3a-t)
A pressure tube charged with 2a-h (100 mg, 1 eq.), K3PO4 (2 eq.), Pd(PPh3)4 (0.05 eq.) and the
respective boronic acid (2.0 eq.) was evacuated and backfilled with argon for 3 times. Then, dry 1,4-
dioxane (3 ml) was added and the pressure tube was sealed with a teflon cap. The reaction mixture
was stirred in a stainless steel heating block at 90 °C for 24h. After cooling to room temperature, the
reaction was quenched with distilled water and extracted with ethyl acetate (3 times). The organic
phase was dried over Na2SO4, concentrated in vacuo and purified by column chromatography
(heptane/ethyl acetate) to obtain precursors 3a-t.
General procedure (C) for the synthesis of 1-alkynyl-6-arylbenzo[f]isoquinolines (4a-k)
A pressure tube charged with 100mg (1 eq.) of the respective 4-aryl-3,5-bis(alkynyl)pyridine dissolved
in 3 ml Xylene was treated with 30 eq. MsOH. The pressure tube was sealed with a teflon cap and
stirred at room temperature for 1h, 10 min (3d), 5min (3h) or in a stainless steel heating block at 90
°C for 2 h (3o,p). The reaction mixture was neutralized with a saturated aqueous solution of NaHCO3
and extracted with ethyl acetate (3 times). The organic phase was dried over Na2SO4, concentrated in
vacuo and purified by column chromatography (heptane/ethyl acetate) to obtain compounds 4a-k.
General procedure (D) for the synthesis of 5,9-diaryl-naphtho[2,1,8-def]isoquinolines (5a-o)
If not otherwise stated, a pressure tube is charged with 100mg (1.0 eq.) of the respective 4-aryl-3,5-
bis(alkynyl)pyridine and treated with 60 eq. MsOH. The pressure tube was sealed with a teflon cap
and stirred in a stainless steel heating block at 120 °C for 12h or 24h (3d,h). After cooling to room
temperature, the reaction was neutralized with a saturated aqueous solution of NaHCO3 and extracted
with ethyl acetate (3 times). The organic phase was dried over Na2SO4, concentrated in vacuo and
purified by column chromatography (heptane/ethyl acetate) to obtain compounds 5a-o.
Gram-scale procedure for the synthesis of 7-methyl-5,9-diphenylnaphtho[2,1,8-def]isoquinoline
(5b)
A 100 ml round bottom flask charged with 1g of 3b (1 eq., 2.7 mmol) was treated with 60 eq. MsOH.
The reaction mixture was placed in an oil bath and stirred at 120 °C for 12h. After cooling to room
temperature, the reaction was neutralized with a saturated aqueous solution of NaHCO3 and extracted
with ethyl acetate (3 times). The organic phase was dried over Na2SO4, concentrated in vacuo and
purified by column chromatography (heptane/EtOAc = 1/1) to obtain compound 5b in 87% yield (0.874
g).
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Analytical Data
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4-chloro-3,5-bis(phenylethynyl)pyridine (2a)
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According to general procedure A, title compound 2a was obtained as a colorless solid in 81% yield
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(95.6 mg) (heptane/EtOAc = 10/1); mp 110–112 °C. H NMR (300 MHz, CDCl3) δ 8.65 (s, 2H), 7.59–
7.63 (m, 4H), 7.37–7.43 (m, 6H). 13C{1H} NMR (75 MHz, CDCl3) δ 150.7, 146.4, 131.9, 129.4, 128.5,
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121.9, 121.1, 98.3, 82.5. IR (ATM, cm-1):
v
= 729 (s), 754 (vs), 896 (m), 911 (m), 966 (m), 1026 (m),
1072 (m), 1201 (m), 1311 (m), 1420 (m), 1490 (s), 1556 (m), 1597 (m), 2211 (m), 3048 (w). MS (EI,
70 eV): m/z (%) = 315 (M+, 34), 314 (23), 313 (M+, 100), 277 (10), 250 (29), 249 (10), 248 (14), 157
(16), 150 (7), 126 (21), 125 (28), 77 (13). HRMS (EI) m/z: [M+] Calcd for C21H12ClN 313.0653; Found
313.0652, [M+] Calcd for C21H1237ClN 315.0623; Found 315.0623.
4-chloro-3,5-bis(p-tolylethynyl)pyridine (2b)
According to general procedure A, title compound 2b was obtained as a colorless solid in 87% yield
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(109.5 mg) (heptane/EtOAc = 10/1); mp 135–137 °C. H NMR (500 MHz, CDCl3) δ 8.62 (s, 2H), 7.49
(d, J = 8.0 Hz, 4H), 7.20 (d, J = 7.9 Hz, 4H), 2.39 (s, 6H). 13C{1H} NMR (126 MHz, CDCl3) δ 150,7,
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145,9, 139,7, 131,8, 129,2, 121,1, 118,9, 98,4, 82,1, 21,6. IR (ATM, cm-1):
v
= 705 (m), 729 (m), 773
(m), 818 (vs), 888 (m), 1181 (w), 1403 (m), 1418 (m), 1508 (m), 1556 (m), 1605 (w), 2211 (m), 2920
(w), 2978 (vw), 3031 (w). MS (EI, 70 eV): m/z (%) = 344 (8), 343 (M+, 34), 342 (29), 341 (M+, 100), 170
(22), 139 (16), 138 (11), 115 (17), 39 (15). HRMS (EI) m/z: [M+] Calcd for C23H16ClN 341.0966; Found
341.0962, [M+] Calcd for C23H1637ClN 343.0936; Found 343.0939.
4-chloro-3,5-bis(m-tolylethynyl)pyridine (2c)
According to general procedure A, title compound 2c was obtained as a colorless solid in 80% yield
(100.6 mg) (heptane/EtOAc = 10/1); mp 114–116 °C. 1H NMR (500 MHz, CDCl3) δ 8.63 (s, 2H), 7.40–
7.44 (m, 4H), 7.28 (pt, J = 7.6 Hz, 2H), 7.22 (d, J = 7.7 Hz, 2H), 2.38 (s, 6H). 13C{1H} NMR (126 MHz,
CDCl3) δ 151.4, 145.7, 138.2, 132.4, 130.2, 129.0, 128.4, 121.9, 120.9, 98.1, 82.4, 21.2. IR (ATM, cm-
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v
= 713 (m), 771 (m), 795 (vs), 890 (m), 1086 (w), 1208 (w), 1337 (w), 1401 (m), 1428 (m), 1482
(m), 1599 (w), 2217 (m), 2918 (w). MS (EI, 70 eV): m/z (%) = 344 (8), 343 (M+, 35), 342 (26), 341 (M+,
100), 276 (11), 263 (11), 170 (14), 139 (19), 138 (11), 115 (17), 39 (11). HRMS (EI) m/z: [M+] Calcd for
C23H16ClN 341.0966; Found 341.0963, [M+] Calcd for C23H1637ClN 343.0940; Found 343.0940.
4-chloro-3,5-bis((4-fluorophenyl)ethynyl)pyridine (2d)
According to general procedure A, title compound 2d was obtained as a colorless solid in 74% yield
(95.2 mg) (heptane/EtOAc = 8/1); mp 141–142 °C. 1H NMR (500 MHz, CDCl3) δ 8.64 (s, 2H), 7.59 (dd,
J = 8.6 Hz, J = 5.4 Hz, 4H), 7.09 (pt, J = 8.6 Hz, 4H). 13C{1H} NMR (126 MHz, CDCl3) δ 163.2
(J = 251.7 Hz), 150.8, 146.1, 133.9 (J = 8.8 Hz), 120.9, 118.0 (J = 3.6 Hz), 115.9 (J = 22.2 Hz), 97.2,
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82.3. 19F NMR (471 MHz, CDCl3) δ -108.8. IR (ATM, cm-1):
v
= 703 (m), 781 (m), 830 (vs), 1014 (w),
1090 (m), 1137 (m), 1154 (s), 1216 (s), 1401 (m), 1424 (m), 1504 (vs), 1558 (m), 1599 (m), 1888 (w),
2219 (m). MS (EI, 70 eV): m/z (%) = 352 (6), 351 (M+, 34), 350 (23), 349 (M+, 100), 286 (22), 174 (13),
144 (22), 143 (20), 75 (10), 57 (12). HRMS (EI) m/z: [M+] Calcd for C21H10ClF2N 349.0464; Found
349.0462, [M+] Calcd for C21H1037ClF2N 351.0435; Found 351.0443.
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4-chloro-3,5-bis((4-(trifluoromethyl)phenyl)ethynyl)pyridine (2e)
According to general procedure A, title compound 2e was obtained as a yellow solid in 75% yield
(123.7 mg) (heptane/EtOAc = 8/1); mp 175–177 °C. 1H NMR (250 MHz, CDCl3) δ 8.70 (s, 2H), 7.71 (d,
J = 8.5 Hz, 4H), 7.65 (d, J = 8.5 Hz, 4H). 13C{1H} NMR (63 MHz, CDCl3) δ 151.8, 146.5, 132.2, 131.1
(J = 32.4 Hz), 125.7, 125.5 (J = 3.8 Hz), 123.7 (J = 272.5 Hz), 120.5, 96.5, 84.5. 19F NMR (471 MHz,
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CDCl3) δ -63.0. IR (ATM, cm-1):
v
= 723 (s), 767 (m), 837 (vs), 898 (m), 1016 (s), 1063 (vs), 1107
(vs), 1156 (s), 1319 (vs), 1403 (m), 1426 (m), 1545 (w), 1613 (m), 1729 (w), 1797 (vw), 1921 (w), 2221
(w), 2854 (w), 2924 (w), 3066 (w). MS (EI, 70 eV): m/z (%) = 452 (8), 451 (M+, 35), 450 (25), 449 (M+,
100), 430 (10), 318 (13), 224 (12), 193 (10). HRMS (EI) m/z: [M+] Calcd for C23H10ClF6N 449.0400;
Found 449.0406, [M+] Calcd for C23H1037ClF6N 451.0371; Found 451.0383.
4-chloro-3,5-bis((4-methoxyphenyl)ethynyl)pyridine (2f)
According to general procedure A, but utilizing 2.6 eq. of 4-ethynylanisole gave title compound 2f as a
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yellow solid in 88% yield (121.6 mg) (heptane/EtOAc = 3/1); mp 121°C. H NMR (250 MHz, CDCl3) δ
8.60 (s, 2H), 7.49–7.57 (m, 4H), 6.85–6.95 (m, 4H), 3.84 (s, 6H). 13C{1H} NMR (63 MHz, CDCl3) δ
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160.4, 151.0, 145.2, 133.4, 121.0, 114.2, 114.1, 98.0, 81.8, 55.3. IR (ATM, cm -1):
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= 773 (s), 830
(vs), 884 (m), 1018 (s), 1107 (m), 1168 (s), 1247 (s), 1290 (m), 1422 (m), 1506 (s), 1556 (m), 1601
(m), 2209 (m), 2840 (w), 2936 (w). MS (EI, 70 eV): m/z (%) = 376 (10), 375 (M+, 34), 374 (24), 373
(M+, 100), 358 (17), 251 (10), 224 (10), 187 (14), 143 (12), 99 (10), 39 (14). HRMS (ESI) m/z: [M+H]+
Calcd for C23H16ClNO2 374.0948; Found 374.0947.
4,4'-((4-chloropyridine-3,5-diyl)bis(ethyne-2,1-diyl))bis(N,N-dimethylaniline) (2g)
According to general procedure A, title compound 2g was obtained as a yellow solid in 80% yield
(117.6 mg) (heptane/EtOAc = 2/1); mp 209–211°C. 1H NMR (250 MHz, CDCl3) δ 8.55 (s, 2H), 7.47 (d,
J = 8.8 Hz, 4H), 6.67 (d, J = 8.9 Hz, 4H), 3.01 (s, 12H). 13C{1H} NMR (63 MHz, CDCl3) δ 150.6, 150.3,
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144.4, 133.1, 121.4, 111.7, 108.7, 99.5, 81.4, 40.1. IR (ATM, cm-1):
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= 750 (m), 810 (vs), 944 (m),
1028 (m), 1224 (s), 1362 (s), 1519 (s), 1556 (m), 1603 (s), 2201 (m), 2802 (m), 2908 (m). MS (EI,
70 eV): m/z (%) = 402 (13), 401 (M+, 37), 400 (30), 399 (M+, 100), 398 (37), 382 (13), 281 (12), 207
(12), 200 (24), 199 (15), 191 (10), 125 (11). HRMS (EI) m/z: [M+] Calcd for C25H22N3Cl1 399.1497;
Found 399.1488, [M+] Calcd for C25H22N337Cl [M+] 401.1467; Found 401.1470.
4-chloro-3,5-bis(thiophen-3-ylethynyl)pyridine (2h)
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According to general procedure A, title compound 2h was obtained as a colorless solid in 78% yield
(94.4 mg) (heptane/EtOAc = 8/1); mp 105–107 °C. 1H NMR (250 MHz, CDCl3) δ 8.61 (s, 2H). 7.65 (dd,
J = 3.0 Hz, J = 1.2 Hz, 2H), 7.34 (dd, J = 5.0 Hz, J = 3.0 Hz, 2H), 7.25 (dd, J = 5.0 Hz, J = 1.2 Hz, 2H).
13C{1H} NMR (63 MHz, CDCl3) δ 150.8, 145.9, 130.4, 129.8, 125.8, 121.1, 93.4, 82.2. (Signal of one
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quaternary carbon is absent, which may relate to signal overlap.) IR (ATM, cm-1):
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= 762 (s), 775
(vs), 806 (s), 863 (m), 894 (m), 999 (m), 1084 (m), 1131 (w), 1173 (w), 1214 (m), 1290 (m), 1356 (m),
1395 (m), 1430 (w), 1562 (w), 1752 (w), 1834 (vw), 2213 (m), 3062 (m). MS (EI, 70 eV): m/z (%) = 328
(8), 327 (M+, 43), 326 (20), 325 (M+, 100), 219 (11), 162 (13), 132 (12), 93 (10), 69 (15), 58 (16), 45
(57). HRMS (EI) m/z: [M+] Calcd for C17H8ClNS2 324.9781; Found 324.9775, [M+] Calcd for
C17H837ClNS2 326.9752; Found 326.9744.
4-phenyl-3,5-bis(phenylethynyl)pyridine (3a)
According to general procedure B, title compound 3a was obtained as a yellow solid in 75% yield (84.8
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mg) (heptane/EtOAc = 10/1); mp 138–140 °C. H NMR (250 MHz, CDCl3) δ 8.76 (s, 2H), 7.66–7.72
(m, 2H), 7.47–7.57 (m, 3H), 7.24–7.33 (m, 10H). 13C{1H} NMR (63 MHz, CDCl3) δ 152.4, 151.0, 136.1,
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131.5, 129.7, 128.9, 128.8, 128.3, 127.7, 122.4, 119.6, 95.8, 85.3. IR (ATM, cm-1):
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= 750 (vs), 787
(m), 903 (m), 915 (m), 1026 (w), 1133 (m), 1306 (w), 1401 (m), 1440 (m), 1488 (m), 1597 (w), 2213
(w), 3000 (w), 3048 (w), 3079 (w). MS (EI, 70 eV): m/z (%) = 356 (26), 355 (M+, 100), 354 (98), 352
(24), 326 (21), 278 (27), 277 (23), 176 (26), 162 (21), 77 (51), 51 (25). HRMS (EI) m/z: [M+] Calcd for
C27H17N 355.1356; Found 355.1346.
3,5-bis(phenylethynyl)-4-(p-tolyl)pyridine (3b)
According to general procedure B, compound 3b was obtained as a yellow solid in 85% (100 mg)
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(heptane/EtOAc = 10/1); mp 94–96 °C. H NMR (300 MHz, CDCl3) δ 8.76 (s, 2H), 7.61–7.66 (m, 2H),
7.27–7.37 (m, 12H), 2.48 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 151.8, 138.8, 133.1, 131.5, 129.7,
128.7, 128.3, 122.6, 119.3, 95.3, 85.7, 21.5. (Signals of one quaternary and one aromatic carbon are
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absent, which may relate to signal overlap.) IR (ATM, cm-1):
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= 750 (vs), 822 (s), 892 (m), 1269 (w),
1399 (m), 1488 (m), 1597 (w), 1725 (w), 2207 (vw), 2852 (w), 2920 (w), 3023 (w). MS (EI, 70 eV): m/z
(%) = 370 (27), 369 (M+, 100), 368 (55), 354 (42), 352 (20), 176 (36), 162 (19), 77 (57), 51 (26).
HRMS (EI) m/z: [M+] Calcd for C28H19N 369.1512; Found 369.1500.
4-(4-methoxyphenyl)-3,5-bis(phenylethynyl)pyridine (3c)
According to general procedure B, title compound 3c was obtained as a yellow solid in 62% yield (76.6
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mg) (heptane/EtOAc = 8/1); mp 128–130 °C. H NMR (500 MHz, CDCl3) δ 8.74 (s, 2H), 7.71 (d,
J = 8.8 Hz, 2H), 7.28–7.37 (m, 10H), 7.06 (d, J = 8.8 Hz, 2H), 3.91 (s, 3H). 13C{1H} NMR (126 MHz,
CDCl3) δ 160.2, 151.8, 151.1, 131.5, 131.4, 128.8, 128.3, 128.1, 122.5, 119.5, 113.1, 95.6, 85.6, 55.4.
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= 752 (vs), 808 (m), 832 (m), 1020 (m), 1249 (s), 1294 (m), 1401 (m), 1488 (m),
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1513 (m), 1603 (m), 2209 (w), 2840 (w), 2930 (w), 3029 (w), 3054 (w). MS (EI, 70 eV): m/z (%) = 386
(22), 385 (M+, 100), 384 (29), 354 (29), 342 (24), 341 (33), 340 (35), 338 (15), 77 (27). HRMS (EI) m/z:
[M+] Calcd for C28H19NO 385.1461; Found 385.1462.
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According to general procedure B, title compound 3d was obtained as a colorless solid in 55% yield
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(74.4 mg) (heptane/EtOAc = 8/1); mp 117–119 °C. H NMR (500 MHz, CDCl3) δ 8.71 (s, 2H), 7.70–
7.74 (m, 4H), 7.20–7.27 (m, 6H), 7.17 (dd, J = 8.0 Hz, J = 1.7 Hz, 4H). 13C{1H} NMR (126 MHz, CDCl3)
δ 151.7, 150.3, 140.0, 131.4, 130.8 (J = 32.4 Hz), 130.3, 129.0, 128.4, 124.7 (J = 3.7 Hz), 124.1
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(J = 272.3 Hz), 122.1, 119.2, 96.3, 84.8. 19F NMR (471 MHz, CDCl3) δ -62.6. IR (ATM, cm-1):
v
= 734
(s), 750 (vs), 841 (s), 892 (m), 911 (m), 1026 (s), 1069 (vs), 1107 (vs), 1166 (s), 1325 (s), 1442 (m),
1488 (m), 1554 (w), 2209 (w), 2852 (w), 2924 (w), 3027 (w), 3060 (w). MS (EI, 70 eV): m/z (%) = 424
(29), 423 (M+, 100), 422 (77), 354 (14), 352 (13), 351 (15), 346 (12), 176 (12), 77 (24). HRMS (EI) m/z:
[M+] Calcd for C28H16F3N 423.1229; Found 423.1217.
4-phenyl-3,5-bis(p-tolylethynyl)pyridine (3e)
According to general procedure B, title compound 3e was obtained as a yellow solid in 80% yield (89.7
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mg) (heptane/EtOAc = 10/1); mp 119–121 °C. H NMR (250 MHz, CDCl3) δ 8.74 (s, 2H), 7.64–7.74
(m, 2H), 7.46–7.58 (m, 3H), 7.18 (d, J = 8.2 Hz, 4H), 7.10 (d, J = 8.0 Hz, 4H), 2.34 (s, 6H).
13C{1H} NMR (63 MHz, CDCl3) δ 152.2, 150.6, 139.1, 136.1, 131.4, 129.8, 129.1, 128.9, 127.6, 119.9,
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119.3, 96.1, 84.8, 21.5. IR (ATM, cm-1):
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= 701 (s), 742 (vs), 812 (vs), 890 (m), 1020 (m), 1183 (m),
1304 (m), 1440 (m), 1504 (m), 1537 (m), 1554 (m), 1601 (w), 1644 (w), 1824 (w), 2211 (m), 2862 (w),
2916 (w), 3025 (m). MS (EI, 70 eV): m/z (%) = 384 (32), 383 (M+, 100), 382 (53), 368 (36), 290 (13),
277 (12), 183 (31), 176 (28), 91 (27), 65 (23). HRMS (EI) m/z: [M+] Calcd for C29H21N 383.1669; Found
383.1665.
4-(p-tolyl)-3,5-bis(p-tolylethynyl)pyridine (3f)
According to general procedure B, title compound 3f was obtained as a yellow solid in 79% yield (91.2
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mg) (heptane/EtOAc = 10/1); mp 155–157 °C. H NMR (250 MHz, CDCl3) δ 8.73 (s, 2H), 7.62 (d,
J = 8.2 Hz, 2H), 7.32 (d, J = 7.9 Hz, 2H), 7.22 (d, J = 8.2 Hz, 4H), 7.11 (d, J = 8.0 Hz, 4H), 2.47 (s,
3H), 2.35 (s, 6H). 13C{1H} NMR (63 MHz, CDCl3) δ 151.8, 150.8, 139.0, 138.8, 133.1, 131.4, 129.7,
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129.1, 128.3, 119.8, 119.5, 95.8, 85.1, 21.5, 21.4. IR (ATM, cm-1):
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= 760 (s), 810 (vs), 888 (m),
1020 (w), 1177 (w), 1399 (w), 1440 (m), 1508 (m), 1535 (w), 1554 (w), 1607 (w), 2209 (w), 2858 (w),
2914 (w), 3025 (w). MS (EI, 70 eV): m/z (%) = 398 (28), 397 (M+, 100), 396 (38), 383 (13), 382 (48),
290 (13), 182 (36), 176 (36), 91 (27), 65 (22). HRMS (EI) m/z: [M+] Calcd for C30H23N 397.1825; Found
397.1817.
4-(4-methoxyphenyl)-3,5-bis(p-tolylethynyl)pyridine (3g)
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According to general procedure B, title compound 3g was obtained as a yellow solid in 64% yield (77.8
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mg) (heptane/EtOAc = 8/1); mp 133–136 °C. H NMR (500 MHz, CDCl3) δ 8.80 (s, 2H), 7.71 (d,
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3H), 2.35 (s, 6H). 13C{1H} NMR (63 MHz, CDCl3) δ 160.0, 151.5, 150.9, 138.9, 131.4, 129.1, 128.5,
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119.6, 113.0, 95.5, 85.4, 55.3, 21.5. (Signals of one quaternary and one aromatic carbon are absent,
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which may relate to signal overlap.) IR (ATM, cm-1):
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= 767 (s), 806 (vs), 820 (s), 892 (m), 1022 (s),
1039 (s), 1135 (m), 1177 (s), 1253 (s), 1294 (m), 1399 (m), 1440 (s), 1506 (s), 1607 (m), 1892 (w),
2211 (w), 2833 (w), 2918 (w), 3027 (w). MS (EI, 70 eV): m/z (%) = 414 (30), 413 (M+, 100), 412 (24),
398 (14), 382 (15), 191 (15), 183 (30), 177 (23), 176 (24), 91 (20). HRMS (EI) m/z: [M+] Calcd for
C30H23NO 413.1774; Found 413.1762.
3,5-bis(p-tolylethynyl)-4-(4-(trifluoromethyl)phenyl)pyridine (3h)
According to general procedure B, title compound 3h was obtained as a colorless solid in 55% yield
(72.1 mg) (heptane/EtOAc = 8/1); mp 174 °C. 1H NMR (500 MHz, CDCl3) δ 8.76 (s, 2H), 7.75–7.81 (m,
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4H), 7.14 (d, J = 8.2 Hz, 4H), 7.11 (d, J = 8.1 Hz, 4H), 2.35 (s, 6H). 13C{1H} NMR (126 MHz, CDCl3)
δ 151.4, 150.0, 140.1, 139.3, 131.3, 130.8 (q, J = 32.4 Hz), 130.3, 129.2, 124.7 (q, J = 3.7 Hz), 124.1
(q, J = 272.2 Hz), 119.4, 119.1, 96.5, 84.3, 21.5. 19F NMR (471 MHz, CDCl3) δ -62.6. IR (ATM, cm-1):
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= 721 (m), 769 (m), 816 (vs), 841 (m), 892 (m), 1026 (m), 1069 (vs), 1117 (vs), 1325 (vs), 1401
(m), 1442 (w), 1506 (m), 1605 (w), 2209 (w), 2920 (w), 3029 (w). MS (EI, 70 eV): m/z (%) = 452 (32),
451 (M+, 100), 450 (32), 436 (13), 382 (13), 365 (12), 91 (10). HRMS (EI) m/z: [M+] Calcd for
C30H20F3N 451.1542; Found 451.1536.
4-phenyl-3,5-bis(m-tolylethynyl)pyridine (3i)
According to general procedure B, title compound 3i was obtained as a yellow solid in 63% yield (70.3
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mg) (heptane/EtOAc = 10/1); mp 75–78 °C. H NMR (250 MHz, CDCl3) δ 8.75 (s, 2H), 7.64–7.74 (m,
2H), 7.47–7.58 (m, 3H), 7.06–7.22 (m, 8H), 2.31 (s, 6H). 13C{1H} NMR (63 MHz, CDCl3) δ 151.8,
151.6, 138.0, 136.3, 132.0, 129.8, 129.6, 128.7, 128.6, 128.2, 127.6, 122.3, 119.4, 95.7, 85.2, 21.2.
~
IR (ATM, cm-1):
v
= 736 (s), 775 (s), 894 (m), 1041 (w), 1090 (w), 1401 (m), 1442 (m), 1482 (m),
1601 (w), 2207 (w), 2854 (w), 2916 (w), 3023 (w). MS (EI, 70 eV): m/z (%) = 384 (27), 383 (M+, 100),
382 (59), 369 (13), 368 (46), 367 (17), 366 (11), 364 (12), 352 (10), 91 (18). HRMS (EI) m/z: [M+]
Calcd for C29H21N 383.1669; Found 383.1658.
4-(p-tolyl)-3,5-bis(m-tolylethynyl)pyridine (3j)
According to general procedure B, title compound 3j was obtained as a yellow solid in 64% yield (74.1
1
mg) (heptane/EtOAc = 10/1); mp 117–119 °C. H NMR (500 MHz, CDCl3) δ 8.74 (s, 2H), 7.62 (d,
J = 8.1 Hz, 2H), 7.33 (d, J = 7.8 Hz, 2H), 7.16–7.22 (m, 2H), 7.10–7.16 (m, 6H), 2.48 (s, 3H), 2.32 (s,
6H). 13C{1H} NMR (126 MHz, CDCl3) δ 151.8, 151.7, 138.6, 138.0, 133.2, 132.1, 129.8, 129.6, 128.6,
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128.3, 128.2, 122.4, 119.4, 95.5, 85.4, 21.5, 21.2. IR (ATM, cm-1):
v
= 762 (s), 787 (vs), 888 (m),
1016 (s), 1090 (s), 1259 (m), 1397 (w), 1445 (w), 1484 (w), 1556 (w), 1599 (w), 2918 (w), 2961 (w),
3025 (w). MS (EI, 70 eV): m/z (%) = 398 (29), 397 (M+, 100), 396 (43), 383 (15), 382 (50), 381 (14),
380 (12), 365 (12), 364 (12), 182 (16), 91 (17). HRMS (EI) m/z: [M+] Calcd for C30H23N 397.1825;
Found 397.1814.
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4-(4-methoxyphenyl)-3,5-bis(m-tolylethynyl)pyridine (3k)
According to general procedure B, title compound 3k was obtained as a yellow solid in 55% yield (66.2
mg) (heptane/EtOAc = 8/1); mp 113–115 °C. 1H NMR (250 MHz, CDCl3) δ 8.73 (s, 2H), 7.66–7.75 (m,
2H), 7.10–7.24 (m, 8H), 7.01–7.09 (m, 2H), 3.91 (s, 3H), 2.32 (s, 6H). 13C{1H} NMR (63 MHz, CDCl3) δ
160.0, 151.8, 151.2, 138.0, 132.0, 131.4, 129.6, 128.6, 128.4, 128.2, 122.4, 119.3, 113.0, 95.5, 85.5,
~
55.3, 21.2. IR (ATM, cm-1):
v
= 777 (vs), 1020 (vs), 1088 (s), 1181 (m), 1253 (s), 1296 (m), 1445 (m),
1515 (m), 1605 (m), 2207 (w), 2918 (w), 2961 (w), 3025 (w). MS (EI, 70 eV): m/z (%) = 414 (30), 413
(M+, 100), 412 (24), 398 (17), 382 (19), 369 (13), 354 (11), 340 (10), 176 (12), 91 (10), 65 (11). HRMS
(EI) m/z: [M+] Calcd for C30H23NO 413.1774; Found 413.1766.
3,5-bis((4-fluorophenyl)ethynyl)-4-phenylpyridine (3l)
According to general procedure B, title compound 3l was obtained as a yellow solid in 74% yield (83.0
1
mg) (heptane/EtOAc = 8/1); mp 105–107 °C. H NMR (500 MHz, CDCl3) δ 8.75 (s, 2H). 7.66 (dd,
J = 7.8 Hz, J = 1.6 Hz, 2H), 7.50–7.56 (m, 3H), 7.25 (dd, J = 8.8 Hz, J = 5.4 Hz, 4H), 6.98 (pt,
J = 8.7 Hz, 4H). 13C{1H} NMR (126 MHz, CDCl3) δ 162.8 (d, J = 250.9 Hz), 152.4, 150.9, 136.1, 133.5
(d, J = 8.4 Hz), 129.7, 129.0, 127.7, 119.5, 118.5 (d, J = 3.4 Hz), 115.7 (d, J = 22.4 Hz), 94.8, 85.0. 19
F
~
NMR (471 MHz, CDCl3) δ -109.6. IR (ATM, cm-1):
v
= 736 (s), 828 (vs), 892 (m), 1043 (m), 1090 (m),
1154 (m), 1230 (s), 1403 (m), 1440 (m), 1500 (s), 1537 (m), 1601 (m), 1743 (m), 1885 (w), 2213 (w),
2854 (w), 2914 (w), 2986 (w), 3025 (w), 3054 (w). MS (EI, 70 eV): m/z (%) = 392 (27), 391 (M+, 100),
390 (74), 389 (22), 388 (21), 387 (20), 369 (15), 362 (16), 296 (18), 295 (17), 95 (17). HRMS (EI) m/z:
[M+] Calcd for C27H15F2N 391.1167; Found 391.1157.
3,5-bis((4-fluorophenyl)ethynyl)-4-(p-tolyl)pyridine (3m)
According to general procedure B, title compound 3m was obtained as a yellow solid in 78% yield
(90.2 mg) (heptane/EtOAc = 8/1); mp 149–152 °C. 1H NMR (500 MHz, CDCl3) δ 8.74 (s, 2H), 7.59 (d,
J = 8.1 Hz, 2H), 7.27–7.34 (m, 6H), 6.94–7.04 (m, 4H), 2.47 (s, 3H). 13C{1H} NMR (63 MHz, CDCl3) δ
162.8 (d, J = 250.8 Hz), 152.2, 151.0, 139.1, 133.5 (d, J = 8.5 Hz), 132.9, 129.7, 128.4, 119.5, 118.6
(d, J = 3.4 Hz), 115.7 (d, J = 22.1 Hz), 94.6, 85.2, 21.5. 19F NMR (471 MHz, CDCl3) δ -109.7. IR (ATM,
~
cm-1):
v
= 758 (s), 816 (s), 826 (vs), 886 (m), 1012 (m), 1090 (m), 1150 (m), 1224 (s), 1292 (w), 1401
(m), 1442 (m), 1502 (s), 1535 (m), 1599 (m), 1877 (w), 2213 (w), 2856 (w), 2918 (w), 3023 (w). MS
(EI, 70 eV): m/z (%) = 406 (31), 405 (M+, 100), 404 (47), 390 (39), 389 (15), 388 (15), 94 (23), 185
(16), 95 (13), 75 (13). HRMS (EI) m/z: [M+] Calcd for C28H17F2N 405.1324; Found 405.1312.
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3,5-bis((4-fluorophenyl)ethynyl)-4-(4-methoxyphenyl)pyridine (3n)
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According to general procedure B, title compound 3n was obtained as a yellow solid in 62% yield (74.1
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mg) (heptane/EtOAc = 8/1); mp 148–149 °C. H NMR (500 MHz, CDCl3) δ 8.73 (s, 2H), 7.68 (d,
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J = 8.7 Hz, 2H), 7.32 (dd, J = 8.7 Hz, J = 5.4 Hz, 4H), 6.98–7.06 (m, 6H), 3.91 (s, 3H). 13C{1H} NMR
(126 MHz, CDCl3) δ 162.8 (d, J = 250.7 Hz), 160.3, 151.9, 150.9, 133.5 (d, J = 8.4 Hz), 131.3, 128.1,
119.5, 118.5 (d, J = 3.2 Hz), 115.7 (d, J = 22.3 Hz), 113.1, 94.6, 85.2, 55.4. 19F NMR (471 MHz,
~
CDCl3) δ -109.6. IR (ATM, cm-1):
v
= 767 (m), 830 (vs), 892 (w), 1041 (m), 1090 (m), 1150 (s), 1181
(s), 1226 (s), 1253 (s), 1294 (m), 1401 (w), 1445 (m), 1502 (vs), 1537 (m), 1601 (m), 1890 (vw), 2215
(w), 2835 (w), 2901 (w), 2936 (w), 3044 (w). MS (EI, 70 eV): m/z (%) = 422 (32), 421 (M+, 100), 420
(19), 390 (19), 378 (23), 377 (33), 376 (31), 349 (18), 188 (22), 179 (25), 164 (22), 95 (19). HRMS (EI)
m/z: [M+] Calcd for C28H17F2NO 421.1273; Found 421.1274.
4-phenyl-3,5-bis((4-(trifluoromethyl)phenyl)ethynyl)pyridine (3o)
According to general procedure B, title compound 3o was obtained as a yellow solid in 71% yield (77.6
mg) (heptane/EtOAc = 8/1); mp 156 °C. 1H NMR (500 MHz, CDCl3) δ 8.81 (s, 2H), 7.65 (dd,
J = 7.7 Hz, J = 1.9 Hz, 2H), 7.51–7.57 (m, 7H), 7.36 (d, J = 8.0 Hz, 4H). 13C{1H} NMR (126 MHz,
CDCl3) δ 152.7, 152.1, 135.9, 131.7, 130.4 (q, J = 32.7 Hz), 129.6, 129.1, 127.8, 126.2, 125.3 (q,
J = 3.7 Hz), 123.8 (q, J = 272.2 Hz), 118.9, 94.2, 87.6. 19F NMR (471 MHz, CDCl3) δ -62.9. IR (ATM,
~
cm-1):
v
= 725 (m), 738 (m), 837 (s), 896 (m), 1016 (m), 1065 (vs), 1105 (vs), 1166 (s), 1321 (s),
1405 (m), 1556 (w), 1611 (w), 1797 (w), 1850 (vw), 3023 (w), 3052 (w). MS (EI, 70 eV): m/z (%) = 492
(23), 491 (M+, 100), 490 (65), 422 (36), 201 (20), 200 (19), 176 (20), 162 (19), 69 (60), 51 (19). HRMS
(EI) m/z: [M+] Calcd for C29H15F6N 491.1103; Found 491.1095.
4-(p-tolyl)-3,5-bis((4-(trifluoromethyl)phenyl)ethynyl)pyridine (3p)
According to general procedure B, title compound 3p was obtained as a yellow solid in 77% yield (85.8
mg) (heptane/EtOAc = 8/1); mp 170 °C. 1H NMR (500 MHz, CDCl3) δ 8.79 (s, 2H), 7.59 (d, J = 8.1 Hz,
2H), 7.57 (d, J = 8.2 Hz, 4H), 7.41 (d, J = 8.1 Hz, 4H), 7.34 (d, J = 7.9 Hz, 2H), 2.49 (s, 3H).
13C{1H} NMR (63 MHz, CDCl3) δ 153.1, 151.5, 139.4, 132.7, 131.7, 130.5 (q, J = 32.7 Hz), 129.6,
128.5, 126.2, 125.3 (q, J = 3.8 Hz), 123.8 (q, J = 272.4 Hz), 119.2, 94.3, 87.5, 21.5. 19F NMR
~
(471 MHz, CDCl3) δ -62.9. IR (ATM, cm-1):
v
= 723 (m), 762 (m), 816 (s), 837 (s), 898 (m), 1014 (s),
1065 (vs), 1100 (vs), 1166 (m), 1181 (m), 1317 (s), 1442 (w), 1513 (w), 1609 (m), 2920 (w), 3044 (w).
MS (EI, 70 eV): m/z (%) = 506 (28), 505 (M+, 100), 504 (47), 490 (33), 436 (25), 200 (15), 183 (20),
176 (20), 168 (16), 69 (42). HRMS (EI) m/z: [M+] Calcd for C30H17F6N 505.1260; Found 505.1249.
4-(4-methoxyphenyl)-3,5-bis((4-(trifluoromethyl)phenyl)ethynyl)pyridine (3q)
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According to general procedure B, title compound 3q was obtained as a yellow solid in 57% yield (65.7
1
mg) (heptane/EtOAc = 8/1); mp 164–166 °C. H NMR (500 MHz, CDCl3) δ 8.78 (s, 2H), 7.66 (d,
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J = 8.8 Hz, 2H), 7.57 (d, J = 8.2 Hz, 4H), 7.43 (d, J = 8.0 Hz, 4H), 7.06 (d, J = 8.8 Hz, 2H), 3.91 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3) δ 160.3, 152.4, 152.0, 131.7, 131.3, 130.4 (q, J = 32.9 Hz),
128.0, 126.3, 125.3 (q, J = 3.6 Hz), 123.8 (q, J = 272.3 Hz), 118.8, 113.1, 93.8, 87.9, 55.4. 19F NMR
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(471 MHz, CDCl3) δ -62.9. IR (ATM, cm-1):
v
= 725 (m), 767 (m), 804 (m), 826 (s), 835 (s), 1016 (m),
1045 (m), 1065 (s), 1102 (vs), 1164 (m), 1181 (s), 1251 (s), 1296 (m), 1321 (s), 1403 (w), 1445 (m),
1515 (m), 1611 (m), 2215 (vw), 2837 (w), 2924 (w), 2996 (w). MS (EI, 70 eV): m/z (%) = 522 (32), 521
(M+, 100), 520 (17), 409 (17), 408 (21), 195 (15), 176 (18), 169 (17), 145 (14), 69 (46). HRMS (EI) m/z:
[M+] Calcd for C30H17F6NO 521.1209; Found 521.1204.
4-phenyl-3,5-bis(thiophen-3-ylethynyl)pyridine (3r)
According to general procedure B, title compound 3r was obtained as a yellow solid in 71% yield (79.8
mg) (heptane/EtOAc = 8/1); mp 106–109 °C. 1H NMR (250 MHz, CDCl3) δ 8.73 (s, 2H), 7.62–7.70 (m,
2H), 7.45–7.55 (m, 3H), 7.33 (dd, J = 3.0 Hz, J = 1.1 Hz, 2H), 7.24 (dd, J = 5.0 Hz, J = 3.0 Hz, 2H),
6.97 (dd, J = 5.0 Hz, J = 1.2 Hz, 2H). 13C{1H} NMR (63 MHz, CDCl3) δ 151.7, 151.4, 136.2, 129.7,
~
129.5, 129.3, 128.8, 127.6, 125.5, 121.6, 119.4, 90.8, 85.1. IR (ATM, cm-1):
v
= 740 (s), 769 (vs), 859
(m), 903 (w), 997 (m), 1078 (m), 1210 (w), 1261 (w), 1356 (w), 1395 (w), 1442 (m), 1556 (w), 2207
(w), 3095 (w). MS (EI, 70 eV): m/z (%) = 369 (10), 368 (31), 367 (M+, 100), 366 (68), 365 (14),
364 (10), 333 (13), 322 (15), 320 (16), 45 (37). HRMS (EI) m/z: [M+] Calcd for C23H13NS2 367.0484;
Found 367.0474.
3,5-bis((4-methoxyphenyl)ethynyl)-4-phenylpyridine (3s)
According to general procedure B, title compound 3s was obtained as a yellow solid in 69% yield (76.5
mg) (heptane/EtOAc = 3/1); mp 153–155 °C. 1H NMR (250 MHz, CDCl3) δ 8.71 (s, 2H), 7.64–7.71 (m,
2H), 7.45–7.56 (m, 3H), 7.18–7.25 (m, 4H), 6.77–6.85 (m, 4H), 3.80 (s, 6H). 13C{1H} NMR (63 MHz,
CDCl3) δ 160.0, 151.3, 151.1, 136.5, 133.0, 129.8, 128.6, 127.6, 119.6, 114.7, 114.0, 95.6, 84.5, 55.3.
~
IR (ATM, cm-1):
v
= 740 (m), 804 (m), 824 (vs), 1026 (s), 1170 (s), 1245 (s), 1288 (m), 1438 (m),
1504 (s), 1605 (m), 2205 (m), 2835 (w), 2961 (w). MS (EI, 70 eV): m/z (%) = 416 (33), 415 (M+, 100),
414 (13), 400 (12), 329 (12), 328 (19), 327 (11), 164 (11), 163 (11), 44 (15). HRMS (EI) m/z: [M+]
Calcd for C29H21NO2 415.1567; Found 415.1567.
4,4'-((4-phenylpyridine-3,5-diyl)bis(ethyne-2,1-diyl))bis(N,N-dimethylaniline) (3t)
According to general procedure B, title compound 3t was obtained as a yellow solid in 72% yield (79.1
mg) (heptane/EtOAc = 2/1); mp 196–198 °C. 1H NMR (500 MHz, CDCl3) δ 8.67 (s, 2H), 7.69–7.72 (m,
2H), 7.43–7.53 (m, 3H), 7.13–7.17 (m, 4H), 6.57–6.60 (m, 4H), 2.96 (s, 12H). 13C{1H} NMR (126 MHz,
CDCl3) δ 150.4, 150.4, 150.3, 136.7, 132.6, 130.0, 128.4, 127.4, 120.0, 111.6, 109.3, 96.9, 84.0, 40.1.
~
IR (ATM, cm-1):
v
= 746 (s), 816 (vs), 968 (m), 1059 (m), 1181 (m), 1222 (m), 1354 (m), 1440 (m),
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1515 (m), 1603 (m), 2195 (m), 2809 (w), 2893 (m). MS (EI, 70 eV): m/z (%) = 441 (M+, 12), 341 (15),
327 (11), 282 (14), 281 (49), 208 (21), 207 (100), 73 (20). HRMS (ESI) m/z: [M+H]+ Calcd for C31H27N3
442.228; Found 442.228.
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6-phenyl-1-(phenylethynyl)benzo[f]isoquinoline (4a) d
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According to general procedure C, title compound 4a was obtained as a yellow oil in 87% yield (87.3
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mg) (heptane/EtOAc = 2/1); Rf 0.25 (heptane/EtOAc 3:1). H NMR (250 MHz, CDCl3) δ 10.42 (dd,
J = 8.4 Hz, J = 1.3 Hz, 1H), 9.15 (s, 1H), 9.01 (s, 1H), 7.99 (dd, J = 8.2 Hz, J = 1.4 Hz, 1H), 7.65–7.80
(m, 5H), 7.44–7.57 (m, 8H). 13C{1H} NMR (63 MHz, CDCl3) δ 151.7, 151.2, 141.2, 139.8, 133.4, 133.2,
131.5, 129.9, 129.5, 128.9, 128.8, 128.7, 128.5, 127.9, 127.0, 126.8, 126.5, 125.4, 123.1, 114.3, 97.3,
89.3. (Signal of one quaternary carbon is absent, which may relate to signal overlap.) IR (ATM, cm-1):
~
v
= 727 (vs), 752 (vs), 771 (s), 824 (m), 900 (m), 1026 (m), 1069 (m), 1133 (m), 1160 (m), 1208 (m),
1335 (m), 1401 (m), 1442 (m), 1490 (m), 1562 (m), 1597 (m), 1731 (w), 2203 (w), 2850 (w), 2922 (m),
3023 (w), 3052 (w). MS (EI, 70 eV): m/z (%) = 356 (26), 355 (M+, 100), 354 (67), 353 (12), 352 (17),
351 (12), 278 (14), 277 (14), 77 (16). HRMS (EI) m/z: [M+] Calcd for C27H17N 355.1356; Found
355.1356.
8-methyl-6-phenyl-1-(phenylethynyl)benzo[f]isoquinoline (4b)
According to general procedure C, title compound 4b was obtained as a yellow solid in 89% yield
1
(89.3 mg) (heptane/EtOAc = 2/1); mp 143–145 °C. H NMR (250 MHz, CDCl3) δ 10.30 (d, J = 8.7 Hz,
1H), 9.12 (s, 1H), 8.98 (s, 1H), 7.66–7.81 (m, 4H), 7.42–7.63 (m, 9H), 2.51 (s, 3H). 13C{1H} NMR
(63 MHz, CDCl3) δ 151.6, 151.1, 140.9, 140.0, 139.1, 133.6, 133.3, 131.5, 129.9, 128.9, 128.6, 128.5,
~
128.2, 127.8, 127.3, 126.7, 126.6, 126.4, 125.6, 123.1, 114.1, 97.1, 89.4, 21.8. IR (ATM, cm-1):
v
= 684 (vs), 705 (s), 752 (vs), 822 (m), 900 (m), 1072 (w), 1205 (m), 1313 (w), 1442 (m), 1490 (m),
1560 (m), 1618 (w), 1739 (w), 2852 (w), 2918 (w), 3015 (w). MS (EI, 70 eV): m/z (%) = 370 (31), 369
(M+, 100), 368 (25), 355 (10), 354 (39), 353 (16), 352 (25), 351 (13), 176 (17), 77 (23). HRMS (EI) m/z:
[M+] Calcd for C28H19N 369.1512; Found 369.1507.
6-phenyl-1-(phenylethynyl)-8-(trifluoromethyl)benzo[f]isoquinoline (4c)
According to general procedure C, title compound 4c was obtained as a yellow solid in 96% yield (95.8
mg) (heptane/EtOAc = 2/1); mp 128–131 °C.1H NMR (500 MHz, CDCl3) δ 10.55 (d, J = 8.9 Hz, 1H),
9.20 (s, 1H), 9.05 (s, 1H), 8.28 (s, 1H), 7.95 (dd, J = 8.9 Hz, J = 1.8 Hz, 1H), 7.70–7.74 (m, 2H), 7.51–
7.60 (m, 5H), 7.44–7.51 (m, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 152.1, 151.3, 141.2, 138.8, 133.1,
132.3, 131.6, 131.5, 130.3 (q, J = 32.9 Hz), 129.8, 129.2, 128.8, 128.7, 128.3, 127.6, 127.1, 126.8,
124.0 (q, J = 4.0 Hz), 124.0 (q, J = 272.8 Hz), 122.4 (q, J = 3.2 Hz), 122.6, 114.7, 98.1, 88.6. 19F NMR
~
(471 MHz, CDCl3) δ -62.4. IR (ATM, cm-1):
v
= 729 (m), 756 (s), 835 (m), 851 (m), 900 (m), 1084 (s),
1117 (vs), 1158 (s), 1286 (m), 1315 (s), 1442 (w), 1492 (w), 1562 (w), 1597 (w), 2852 (w), 2922 (w),
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3023 (w). MS (EI, 70 eV): m/z (%) = 424 (26), 423 (M+, 100), 422 (37), 354 (15), 352 (12), 351 (11), 77
(15). HRMS (EI) m/z: [M+] Calcd for C28H16F3N 423.1229; Found 423.1218.
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6-(p-tolyl)-1-(p-tolylethynyl)benzo[f]isoquinoline (4d)
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According to general procedure C, title compound 4d was obtained as a yellow solid in 94% yield
(94.5 mg) (heptane/EtOAc = 2/1); mp 175–178 °C. 1H NMR (250 MHz, CDCl3) δ 10.34 (dd, J = 8.4 Hz,
4J = 1.2 Hz, 1H), 9.05 (s, 1H), 8.91 (s, 1H), 7.92 (dd, J = 8.1 Hz, J = 1.5 Hz, 1H), 7.55–7.70 (m, 3H),
7.52 (d, J = 8.1 Hz, 2H), 7.34 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 7.1 Hz, 2H),
2.40 (s, 3H), 2.35 (s, 3H). 13C{1H} NMR (63 MHz, CDCl3) δ 151.5, 150.9, 141.2, 139.2, 137.6, 136.9,
133.6, 133.1, 131.4, 129.7, 129.6, 129.4, 129.2, 128.7, 127.0, 126.8, 126.4, 125.3, 120.0, 97.5, 88.7,
21.6, 21.3. (Signals of two quaternary carbons are absent, which may relate to signal overlap.) IR
~
(ATM, cm-1):
v
= 729 (vs), 767 (s), 810 (s), 909 (m), 1109 (w), 1208 (w), 1403 (w), 1447 (m),
1508 (m), 1560 (w), 1607 (w), 2852 (w), 2918 (w), 3025 (w). MS (EI, 70 eV): m/z (%) = 384 (29), 383
(M+, 100), 382 (31), 368 (27), 367 (9), 183 (16), 176 (12). HRMS (EI) m/z: [M+] Calcd for C29H21N
383.1669; Found 383.1660.
8-methyl-6-(p-tolyl)-1-(p-tolylethynyl)benzo[f]isoquinoline (4e)
According to general procedure C, title compound 4e was obtained as a yellow solid in 93% yield (92.6
1
mg) (heptane/EtOAc = 2/1); mp 178–180 °C. H NMR (300 MHz, CDCl3) δ 10.31 (d, J = 8.7 Hz, 1H),
9.10 (s, 1H), 8.96 (s, 1H), 7.78 (s, 1H), 7.55–7.64 (m, 3H), 7.68 (s, 1H), 7.40–7.45 (m, 2H), 7.35 (d, J
= 7.8 Hz, 2H), 7.25–7.29 (m, 2H), 2.51 (s, 3H), ), 2.50 (s, 3H), 2.44 (s, 3H). 13C{1H} NMR (75 MHz,
CDCl3) δ 151.4, 150.9, 140.8, 139.1, 139.0, 137.5, 137.1, 133.7, 133.1, 131.4, 129.7, 129.4, 129.2,
~
128.1, 127.4, 126.7, 126.5, 126.5, 125.5, 120.1, 114.2, 97.3, 88.8, 21.8, 21.6, 21.3. IR (ATM, cm-1):
v
= 736 (s), 783 (s), 814 (vs), 900 (s), 1109 (m), 1203 (w), 1436 (m), 1508 (m), 1560 (w), 1618 (w),
1737 (w), 2199 (w), 2852 (w), 2916 (m), 3017 (w). MS (EI, 70 eV): m/z (%) = 398 (30), 397 (M+, 100),
396 (19), 383 (11), 382 (34), 183 (22), 169 (11). HRMS (ESI) m/z: [M+H]+ Calcd for C30H23N 398.1909;
Found 398.1904.
6-(p-tolyl)-1-(p-tolylethynyl)-8-(trifluormethyl)benzo[f]isoquinoline (4f)
According to general procedure C, title compound 4f was obtained as a yellow solid in 92% yield (91.6
1
mg) (heptane/EtOAc = 2/1); mp 177–179 °C. H NMR (300 MHz, CDCl3) δ 10.56 (d, J = 8.9 Hz, 1H),
9.17 (s, 1H), 9.03 (s, 1H), 8.30 (s, 1H), 7.93 (dd, J = 8.9 Hz, J = 1.9 Hz, 1H), 7.81 (s, 1H), 7.61 (d,
J = 8.1 Hz, 2H), 7.42 (d, J = 8.2 Hz, 2H), 7.37 (d, J = 8.2 Hz, 2H), 7.28 (d, J = 7.9 Hz, 2H), 2.50 (s,
3H), 2.45 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 151.9, 151.1, 141.2, 139.6, 138.2, 135.9, 133.2,
132.2, 131.7, 131.4, 130.6 (q, J = 32.5 Hz), 129.6, 129.5, 127.6, 127.2, 126.7, 124.1 (q, J = 4.2 Hz),
122.3 (q, J = 272.7 Hz), 122.2 (q, J = 3.1 Hz), 119.6, 114.9, 98.3, 88.1, 21.6, 21.3. (Signal of one
aromatic carbon is absent, which may relate to signal overlap.) 19F NMR (282 MHz, CDCl3) δ -62.3. IR
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v
= 736 (m), 816 (s), 855 (m), 903 (s), 1084 (s), 1121 (vs), 1170 (s), 1286 (m), 1315 (s),
(ATM, cm-1):
1372 (w), 1453 (w), 1510 (m), 1566 (w), 1611 (w), 1908 (vw), 2201 (w), 2852 (w), 2918 (w), 3031 (w).
MS (EI, 70 eV): m/z (%) = 452 (32), 451 (M+, 100), 450 (18), 436 (20), 382 (8), 182 (12). HRMS (EI)
m/z: [M+] Calcd for C30H20F3N 451.1542; Found 451.1532.
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6-(4-fluorophenyl)-1-((4-fluorophenyl)ethynyl)benzo[f]isoquinoline (4g)
According to general procedure C, title compound 4g was obtained as a yellow solid in 94% yield
(93.8 mg) (heptane/EtOAc = 2/1); mp 127–129 °C. 1H NMR (300 MHz, CDCl3) δ 10.32–10.38 (m, 1H),
9.14 (s, 1H), 8.99 (s, 1H), 7.89–7.96 (m, 1H), 7.61–7.79 (m, 5H), 7.42–7.54 (m, 2H), 7.11–7.26 (m,
4H). 13C{1H} NMR (75 MHz, CDCl3) δ 162.9 (d, J = 250.9 Hz), 162.5 (d, J = 247.2 Hz), 151.7, 151.2,
140.1, 135.7 (d, J = 3.4 Hz), 133.4 (d, J = 8.4 Hz), 133.4, 133.2, 131.5 (d, J = 8.1 Hz), 129.5, 128.9,
126.8, 126.7, 126.6, 126.6, 125.6, 19.1 (d, J = 3.5 Hz), 116.0 (d, J = 22.3 Hz), 115.5 (d, J = 21.4 Hz),
~
114.1, 96.2, 88.9. 19F NMR (282 MHz, CDCl3) δ -114.1, -109.5. IR (ATM, cm-1):
v
= 727 (vs), 762 (s),
826 (vs), 911 (m), 1012 (m), 1090 (m), 1154 (s), 1220 (s), 1504 (s), 1599 (m), 2854 (w), 2922 (w),
3044 (w). MS (EI, 70 eV): m/z (%) = 392 (26), 391 (M+, 100), 390 (63) 389 (10), 388 (11), 185 (13).
HRMS (EI) m/z: [M+] Calcd for C27H15F2N 391.1167; Found 391.1158.
6-(4-fluorophenyl)-1-((4-fluorophenyl)ethynyl)-8-methylbenzo[f]isoquinoline (4h)
According to general procedure C, title compound 4h was obtained as a yellow solid in 91% yield
(91.3 mg) (heptane/EtOAc = 2/1); mp 138–140 °C. 1H NMR (300 MHz, CDCl3) δ 10.24 (d, J = 8.6 Hz,
1H), 9.11 (s, 1H), 8.96 (s, 1H), 7.64–7.72 (m, 4H), 7.59 (dd, J = 8.7 Hz, J = 1.7 Hz, 1H), 7.45–7.52 (m,
2H), 7.12–7.27 (m, 4H), 2.52 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 162.9 (d, J = 250.8 Hz), 162.5
(d, J = 247.1 Hz), 162.5, 151.6, 151.1, 139.8, 139.3, 135.9 (d, J = 3.4 Hz), 133.6, 133.3, 133.4 (d, J =
8.5 Hz), 131.4 (d, J = 7.9 Hz), 128.3, 127.3, 126.6, 126.4, 126.3, 125.7, 119.2 (d, J = 3.6 Hz), 116.0
(d, J = 22.2 Hz), 115.5 (d, J = 21.4 Hz), 113.9, 96.1, 89.0, 21.8. 19F NMR (282 MHz, CDCl3) δ -114.3, -
~
109.7. IR (ATM, cm-1):
v
= 736 (s), 781 (s), 822 (vs), 1010 (m), 1090 (m), 1154 (s), 1222 (s), 1504
(s), 1562 (w), 1599 (m), 1702 (w), 2852 (w), 2916 (w), 3025 (w). MS (EI, 70 eV): m/z (%) = 406 (29),
405 (M+, 100), 404 (22), 390 (33), 389 (12), 388 (12), 194 (11). HRMS (EI) m/z: [M+] Calcd for
C28H17F2N 405.1324; Found 405.1314.
6-(4-(trifluoromethyl)phenyl)-1-((4-(trifluoromethyl)phenyl)ethynyl)benzo[f]isoquinoline (4i)
According to general procedure C, title compound 4i was obtained as a yellow solid in 86% yield (86.1
mg) (heptane/EtOAc = 2/1); mp 174–176 °C. 1H NMR (500 MHz, CDCl3) δ 10.33 (d, J = 8.4 Hz, 1H),
9.20 (s, 1H), 9.04 (s, 1H), 7.90 (d, J = 7.9 Hz, 1H), 7.82 (d, J = 8.0 Hz, 4H), 7.78 (d, J = 8.3 Hz, 1H),
7.71–7.76 (m, 4H), 7.67 (d, J = 8.0 Hz, 2H). 13C{1H} NMR (126 MHz, CDCl3) δ 152.2, 151.8, 143.4,
139.9, 133.5, 133.0, 131.7, 130.8 (q, J = 32.8 Hz), 130.2, 130.2 (q, J = 32.4 Hz), 129.4, 129.3, 126.9,
126.7, 126.7, 126.5, 125.7, 125.6 (q, J = 3.7 Hz), 125.5 (q, J = 3.8 Hz), 124.1 (q, J = 272.2 Hz), 123.8
(q, J = 272.2 Hz), 113.7, 95.8, 91.3. (Signal of one aromatic carbon is absent, which may relate to
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