Synthesis and Photophysical Properties of a Series of Pyrazine-Based Push–Pull Chromophores

Article abstract of DOI:10.1002/ejoc.201601204

Eighteen push–pull pyrazine fluorophores are described. Methoxy, dimethylamino, and diphenylamino groups were used as electron-donating groups (EDGs), and six π-conjugated systems consisting of multiple bonds and 1,4-phenylene moieties were used to connec

Full text of DOI:10.1002/ejoc.201601204

A Journal of
Accepted Article
Title: Synthesis and photophysical properties of a series of pyrazine-based push-pull
chromophores
Authors: Kellyn Hoffert; Raphael Durand; Sebastien Gauthier; Franc¸oise Robin-Le
Guen; Sylvain Achelle
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European Journal of Organic Chemistry
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FULL PAPER
Pyrazine chromophores
Kellyn Hoffert, Raphaël J. Durand,
Sébastien Gauthier, Françoise Robvin-le
Guen, Sylvain Achelle*
Page No. – Page No.
Text for Table of Contents
Synthesis and photophysiscal
properties of a series of pyrazine-
based push-pull chromophores
1
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European Journal of Organic Chemistry
10.1002/ejoc.201601204
Synthesis and photophysical properties of a series of pyrazine-based push-pull
chromophores.
Kellyn Hoffert,[a] Raphaël J. Durand,[a] Sébastien Gauthier,[a] Françoise Robin-le Guen,[a]
Sylvain Achelle*[a]
[a]Institut des Sciences Chimiques de Rennes, UMR CNRS 6226, IUT de Lannion, rue
Edouard Branly, BP 30219, F22302 Lannion Cedex, France.
Corresponding author: *E-mail: sylvain.achelle@univ-rennes1.fr
Abstract
A series of push-pull pyrazine fluorophores was described. Methoxy, dimethylamino and
diphenylamino groups were used as electron-donating groups, and six π-conjugated systems
consisting of multiple bonds and 1,4-phenylene moieties were used for the connection to the
pyrazine core. The chromophores were obtained by Knoevenagel condensations and
palladium catalyzed cross couplings starting from commercially available 2-methyl or 2-
chloropyrazine. The optical absorption and emission properties of these chromophores were
studied in different solvents. Some of them revealed to be highly emissive and exhibit a
strong emission solvatochromism that suggests a highly polar emitting state, characteristic of
compounds that undergo intramolecular charge transfer (ICT). The influences of the nature of
the electron donating group and the π-conjugated system on the emission and ICT were
carefully studied.
Keywords: Pyrazine, Donor-acceptor systems, Conjugation, Fluorescence, Intramolecular
Charge Transfer.
Introduction
2
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European Journal of Organic Chemistry
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Push–pull structures composed of a π-conjugated core substituted by electron-donating (D)
and electron-attracting (A) groups have attracted significant interest due to the potential
applications related to strong emission behavior and nonlinear optical properties.1 In such D-
π-A structure, intramolecular charge transfer (ICT) leads to polarization of the chromophore
and generation of a molecular dipole.2 Photophysical properties of push-pull molecules can be
easily tuned by varying various parameters such as the nature of the electron donating and
withdrawing couple and the length of the conjugation pathway.3
Pyrazine is a six-membered heterocycle with two nitrogen atoms (1,4-diazine). Due to its
electron-deficient character, this heterocycle can be used as the electron-withdrawing part in
push-pull structures. The incorporation of pyrazine units in luminescent materials has been
recently reviewed.4 The luminescence of push-pull pyrazine chromophores can be easily
tuned by external stimuli.5 The ability of protonation, hydrogen bond formation, and chelation
of the nitrogen atom can be efficiently used for sensing applications. Pyrazine push-pull
derivatives are known for their strong positive solvatochromism and their halochromic
properties.6 Some pyrazine fluorophores have been designed as fluorescent protein sensors.7
Some pyrazine derivatives have been also described as emitting layer in organic light emitting
diodes8 or used as chromophores for dye-sensitized solar cells.9 Pyrazine fragments have also
been incorporated in the structure of second order10 (frequency doubling) and third order8,11
(two photon absorption) nonlinear optical (NLO) chromophores. Even if the NLO responses
of pyrazine derivatives are generally lower than their pyrimidine (1,3-diazine) analogues,12
these compounds are generally significantly more emissive.12a,13
The main purpose of the present article is to design, synthesize and study the photophysical
properties of push-pull pyrazine derivatives with six different π-conjugated cores. Our study
was focused on π-conjugated systems consisting of multiple bonds and 1,4-phenylene
3
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European Journal of Organic Chemistry
10.1002/ejoc.201601204
moieties. Influence of the length and composition of the π-linker as well as the nature of the
electron-donating group on the photophysical properties will be thoroughly studied.
Result and Discussion
Synthesis
Styryl derivatives 1 were obtained by Knoevenagel condensation of the corresponding
aldehyde with commercially available 2-methylpyrazine (Scheme 1). Potassium hydroxide in
DMSO (dimsyl potassium), according to the conditions initially described by Pan et al.,14
afforded the condensation products 1 in moderate to good yields, generally without the need
of chromatography purification (except for 1c). Bromine derivative 1d was used as a coupling
partner in Sonogashira and Suzuki cross-coupling conditions to obtain tricyclic linear
oligomers 2 and 3 respectively (Scheme 1). Good yields (73-85 %) were obtained for Suzuki
cross coupling reaction. The yields of Sonogashira coupling were more limited (43-65 %).
Scheme 1: Synthesis of compounds 1-3. (i) pR-C6H4-CHO, KOH, DMSO, rt, 15 h. (ii) pR-
C6H4-C≡CH, Pd(PPh3)2Cl2, CuI, HN(iPr)2, , 15 h. (iii) pR-C6H4-B(OH)2, Pd(PPh3)4,
K2CO3aq, Toluene/EtOH, , 15 h.
Due to the electron-withdrawing character of the pyrazine ring, palladium-catalyzed cross-
coupling reactions can be performed from commercially available 2-chloropyrazine without
4
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European Journal of Organic Chemistry
10.1002/ejoc.201601204
the use of specialized and expensive ligands.15 Indeed the electron-withdrawing character of
this heterocycle makes possible the oxidative addition of palladium in the chlorine-carbon
bond.16 Using Pd(PPh3)4 as a catalyst, Suzuki cross-coupling reactions afforded compounds 4
and 6 in good yields (Scheme 2). Ethynylpyrazines 5 were obtained by Sonogashira coupling
using Pd(PPh3)2Cl2 and CuI as a catalytic mixture (Scheme 2). In all cases, performing the
reaction in a pressurized tube permits a reduction in reaction time and increases the yields.
Scheme 2: Synthesis of compounds 4-7. (i) corresponding boronic acid, Pd(PPh3)4, K2CO3aq,
Toluene/EtOH, , 15 h. (ii) corresponding terminal alkyne, Pd(PPh3)2Cl2, CuI, HN(iPr)2, ,
15 h.
All the compounds were thoroughly characterized by 1H, 13C NMR and high resolution mass
spectra. The stereochemistry of the double bonds in compounds 1-3 was unequivocally
1
established on the basis of the coupling constant for the vinylic protons in the H spectra (J 
16Hz).
Optical properties
5
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European Journal of Organic Chemistry
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The UV/Vis and photoluminescence (PL) spectroscopic data of compounds 1-6 measured in
CH2Cl2 at room temperature are presented in Table 1. The analyses were carried out using
low concentrated solutions (1.0-3.0  10 -5 M). The absorption spectra showed a π-π* transition
in the UV region at max = 318-397 nm accompanied by one or two extra bands at higher
energies. All compounds are luminescent with high quantum yield (up to 0.81) in some cases.
It should be noted that the quantum yields of compounds 1b and 1c that we measured were
significantly higher than previously reported.12b Except for the phenylene coupounds 4, the
methoxy derivatives exhibit emission maxima in the purple-blue region, whereas the amino
derivatives emit in the green-yellow region upon irradiating the solution. As an example,
spectra for derivatives 1b, 2a and 3c in dichloromethane are shown on Fig.1. The Stokes
shifts are rather large, and significantly higher for amino derivatives than for their methoxy
analogues. Both the absorption and emission maxima were found to be red-shifted when
going from a phenylene (4) to a phenylenethynylene (5) and a phenylenvinylene (1) linker. As
previously observed on the pyrimidine series,17 extension of the π-conjugated linker by a
second phenylene fragment (1 vs 2 or 3, 4 vs 6) resulted in a moderate modification of the
absorption maxima. However, a more important red shift of the emission is observed leading
to an increase of the Stokes shift. In the case of methoxy derivatives, this is also associated
with a dramatic enhancement of the fluorescence quantum yield, this tendency is less obvious
for amino derivatives. When comparing compounds 2 with compounds 3, it appears that the
ethynylene linker between the two phenyl rings had a limited influence on the position of
absorption and emission maxima. On the contrary, addition of a vinylene linker between the
pyrazine core and the first phenyl ring (2 versus 6) leads to a significant red-shift of both
absorption and emission maxima.
Table 1: UV/Vis and PL data in CH2Cl2.
PL
Stokes shift
UV/vis max, nm
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European Journal of Organic Chemistry
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Compda
cm–1
5700
b
(, mM–1·cm–1)

max, nm
431
F
293 (18.8), 346 (30.8)
0.03
0.40
0.78
0.79
0.62
0.79
0.46
0.69
0.72
0.14
0.59
0.68
0.28
0.17
0.52
0.81
0.60
0.79
1a
1b
1c
2a
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
6c
271 (8.7), 329 (10.3), 391 (28.5)
297 (19.5), 397 (25.5)
522
528
449
579
563
451
570
557
386
489
496
403
523
517
416
530
516
6418
6250
5739
8838
8348
6317
8771
8431
5539
7799
7161
5674
7907
7113
6173
8380
7358
300 (18.4), 357 (41.1)
292 (28.0), 383 (31.9)
309 (0.69), 383 (0.81)
300sh (13.8), 351 (29.3)
294 (18.1), 380 (32.3)
303 (35.0), 379 (39.1)
266 (23.5), 291 (27.4), 318sh (18.8)
325 (13.4), 354 (13.7)
210 (19.4), 304 (26.1), 366 (41.2)
288sh (17.6), 313sh (23.9), 328 (25.2)
277 (13.2), 324 (13.6), 370 (28.2)
288 (20.1), 378 (29.5)
270sh (15.1), 331 (38.0)
288 (20.1), 367 (27.8)
297 (33.7), 374 (42.3)
a
b
All spectra were recorded at room temperature at c = 1.0  10–5 M to 3.0  10–5. Fluorescence
quantum yield (10%) determined relative to 9,10-Bis-phenylethynyl-anthracene in cyclohexane (F
= 1.00).18
7
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European Journal of Organic Chemistry
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Figure 1: Normalized UV/Vis (dashed line) and emission spectra (solid lines) of compounds
1b (green), 2a (blue) and 3c (red).
In push-pull compounds, the effect of the polarity on the position of the absorption band can
be moderate.19 In contrast, significant emission solvatochromism can be observed in such
fluorescent dyes.6,17,20 This solvatochromic behavior results from the stabilization of the
highly polar emitting state by polar solvents.21 The emission properties of compounds 1-6
were measured in seven aprotic solvents of various polarity. The results of these
investigations are summarized in Table 2. It should be noted that, in some cases, in low polar
solvents (heptane, toluene) two well-developed emission bands are observed due to increase
of the vibronic structure. All compounds show a marked positive emission solvatochromism:
increasing solvent polarity as predicted by the Dimroth-Reichardt polarity parameter
(ET(30))22 leads to a pronounced bathochromic shift of the emission band. As examples, the
PL spectra for compound 3b, and color change under UV irradiation for compound 3c in
various solvents are shown in Fig. 2 and 3.
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European Journal of Organic Chemistry
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Table 2: Emission solvatochromism of pyrazine derivatives 1-6 in various aprotic solvents.
Heptane
Toluene
THF
CH2Cl2
ET(30)a = 40.7
max nm
431
Acetone
ET(30)a = 42.2
max nm
429
MeCN
ET(30)a = 45.6
max nm
442
DMSO
ET(30)a = 45.1
max nm
450
ET(30)a = 30.9 ET(30)a = 33.9 ET(30)a = 37.4
Compd
max nm
398
max nm
412
max nm
418
497
493
431
560
522
432
546
524
372
459
458
386
493
476
400
512
484
1a
1b
1c
2a
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
6c
443
470
522
532
549
560
428
461
528
532
549
552
390/412
431/449
425/449
396/408
461
405/422
478
449
451
464
471
b
b
579
629
-
-
457
563
597
622
461
632
602
387
517
519
421
594
558
432
601
571
635
469
645
608
396
526
514
431
601
561
439
623
577
420
451
455
483
570
604
450
474
557
571
358
365
386
386
400
433
480
501
420
437
496
494
365
376
402
413
409
442
523
564
414
437
517
531
364/378
399/417
410
382
416
422
450
530
579
432
516
538
a Dimroth–Reichardt polarity parameter, kJmol–1. b no signal detected
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European Journal of Organic Chemistry
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Figure 2: Normalized emission spectra of 3b in different aprotic solvents.
Figure 3: Fluorescence colour changes of 3c in various solvents (from left to right: heptane,
toluene, THF, CH2Cl2, MeCN, DMSO. Picture was taken in the dark upon irradiation with a
hand-held UV lamp ( exc = 366 nm)
Studying emission solvatochromism is a way to evaluate ICT in push pull-structures. For all
compounds, the emission maxima were plotted versus ET(30) (Figures 4, S26 and S27). For
all the chromophores, a good linearity was obtained. When comparing the three electron-
donating groups for all the π-conjugated linkers, the solvatochromic range increases in the
following order: -OMe < -NPh2 < -NMe2, in accordance with the electron-donating ability of
these groups, as estimated by Hamett constant.23 When comparing compounds 2 with their 4-
substituted pyrimidine analogues, it appears that the pyrazine derivatives exhibits slightly
lower solvatochromic range.24 In the dimethylamino series, the slopes of the corresponding
regression lines indicate that the solvatochromic range increases in the following order: 1b ≈
4b < 3b ≈ 5b ≈ 6b < 2b (Figure 4) and seems to indicate that a vinylene
phenylenethynylenphenylene linker between the pyrazine and the dimethylamino group is the
10
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European Journal of Organic Chemistry
10.1002/ejoc.201601204
most efficient in terms of ICT. The same tendency is observed in diphenylamino series, but
surprisingly not with methoxy derivatives.
Figure 4: Emission maxima (em) as a function of Dimroth-Reichardt polarity parameter for
dimethylamino derivatives 1b, 2b, 3b, 4b, 5b, and 6b.
Conclusion
In summary, a series of eighteen pyrazine push-pull chromophores as synthesized by
Knoevenagel condensation as well as Suzuki and Sonogashira cross coupling reactions. Their
absorption and emission properties were measured and some of the compounds were found to
be highly fluorescent in dichloromethane solution (F up to 0.8). Extension of the π-
conjugated linker revealed to be a mean to dramatically increase the fluorescence intensity of
methoxy derivatives. These chromophores, more particularly the dimethylamino derivatives,
exhibit strong emission solvatochromism, indicating the formation of very polar excited ICT
states. Therefore, these compounds appear as promising fluorescent polarity sensors and
potential NLO chromophores.
11
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Experimental Section
General. All chemicals were purchased from commercial sources and were used without
further purification. Boronic acids used for the synthesis of compounds 6 were obtained
according to reported procedures.25 Compound 1d was obtained as described previously.12a
Analytical thin layer chromatography was performed with silica gel plates (Merk® TCL silica
gel 60 F254) and compounds were detected by irradiation with UV light (365 nm). The
chromatographic purification of compounds was achieved with silica gel (Acros, 60-80
mesh). All air- and moisture-sensitive reactions were carried out in flame-dried glassware that
was subsequently cooled under nitrogen. NMR spectra were acquired at room temperature on
a Bruker AC-300 spectrometer. Chemical shifts are given in parts per million relative to TMS
(1H, 0.0 ppm) and CDCl3 (13C, 77.0 ppm). Acidic impurities in CDCl3 were removed by
treatment with anhydrous K2CO3. High resolution MALDI MS spectra were measured using
method “dried droplet” on a MALDI mass spectrometer LTQ Orbitrap XL (Thermo Fisher
Scientific, Bremen, Germany) equipped with nitrogen UV laser (337 nm, 60 Hz). The LTQ
Orbitrap instrument was operated in positive-ion mode over a normal mass range (m/z 50–
2000) with the resolution 100,000 at m/z = 400. The used matrix was 2,5-dihydroxybenzoic
acid (DHB). UV/vis spectra were recorded with a UVIKON xm SECOMAM spectrometer
using standard 1 cm quartz cells. Fluorescence spectra were recorded using Spex FluoroMax-
3 Jobin-Yvon Horiba apparatus. Compounds were excited at their absorption maxima
(longest-wavelength absorption band) to record the emission spectra. The F values were
calculated using a well-known procedure using 9,10-diphenylethynylanthracene in
cyclohexane as standard.18 Stokes shifts were calculated by considering the lowest energetic
absorption band.
General procedure for Knoevenagel condensation: The corresponding aldehyde (10 mmol)
and 2-methylpyrazine (936 mg, 10 mmol) were dissolved in DMSO (6 mL). Powdered KOH
12
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European Journal of Organic Chemistry
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(2.2 g, 40 mmol) was added and the reaction mixture was stirred at room temperature for 15 h
and then poured into 200 mL of water. The resulting precipitate was filtered and washed with
water (2 x 150 mL) The crude product was used without further purification (except in case of
1c).
General procedure for Sonogashira cross-coupling reactions for compounds 2 and 5 : A
suspension of the corresponding halogeno derivative (1.0 mmol), Pd(PPh3)2Cl2 (75 mg, 0.10
mmol), and CuI (10mg, 0.05 mmol) in diisopropylamine (10 mL) was degassed three times in
a pressure tube. The acetylene derivative (1.2 mmol) was then added. The mixture was heated
at 80°C overnight. The suspension was then diluted with a mixture of water and
dichloromethane (1:1, 30 mL) and the organic layer was extracted with dichloromethane (2 
30 mL). The combined organic extracts were dried over MgSO4, filtered, and evaporated.
General Procedure for Suzuki cross-coupling reactions for the synthesis of compounds
3, 4, and 6: A stirred mixture of halogeno derivative (1 mmol), arylboronic acid (1.2 mmol),
Pd(PPh3)4 (0.05 mmol), aqueous 1 M sodium carbonate (2.2 mmol, 2.2 mL) and ethanol (1.5
mL) in degassed toluene (10mL) was heated at reflux under nitrogen for 15 h in Schlenk tube.
The reaction mixture was cooled, filtered, and dissolved with a mixture of AcOEt and water
1:1 (50mL) and the organic layer was separated. The aqueous layer was extracted with AcOEt
(2 x 25 mL). The combined organic extracts were dried with MgSO4 and the solvents
evaporated.
(E)-2-(4-methoxystyryl)pyrazine (1a): Cream solid. Yield: 61% (1.29 g) Mp: 109-110°C
(lit.26 104-105°C). 1H NMR (300MHz, CDCl3):  3.85 (s, 3H), 6.93 (d, 2H, J = 8.7 Hz), 7.03
(d, 1H, J = 15.9 Hz), 7.54 (d, 2H, J = 8.7 Hz), 7.70 (d, 1H, J = 15.9 Hz), 8.37 (d, 1H, J = 2.7
13
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European Journal of Organic Chemistry
10.1002/ejoc.201601204
Hz), 8.51 (dd, 1H, J1 = 2.7 Hz, J2 = 1.5 Hz), 8.61 (d, 1H, J = 1.5 Hz). Data similar to the
literature.26
(E)-2-(4-dimethylaminostyryl)pyrazine (1b): Yellow solid. Yield: 65% (1.46 g) Mp: 125-
1
126°C (lit:12b 117-118°C). H NMR (300MHz, CDCl3) :  3.03 (s, 6H), 6.72 (d, 2H, J = 8.7
Hz), 6.94 (d, 1H, J = 15.9 Hz), 7.49 (d, 2H, J = 8.7 Hz), 7.67 (d, 1H, J = 15.9 Hz), 8.31 (d,
1H, J = 2.7 Hz), 8.48 (dd, 1H, J1= 2.7 Hz, J2 = 1.5 Hz), 8.58 (d, 1H, J = 1.5 Hz) Data similar
to the literature.12b
(E)-2-(4-diphenylaminostyryl)pyrazine (1c): Purified by column chromatography
(petroleum ether/EtAcO, 7/3), yellow solid. Yield: 86% (3.00 g) Mp: 140-141°C (lit:12b 135-
1
136°C). H NMR (300MHz, CDCl3) :  7.03 (d, 1H, J = 15.9 Hz), 7.09-7.05 (m, 4H) , 7.14
(dd, 4H, J1 = 8.7 Hz, J2 = 1Hz), 7.30-7.27 (m, 4H), 7.45 (d, 2H, J = 8.7 Hz), 7.68 (d, 1H, J =
15.9 Hz), 8.36 (d, 1H, J = 2.7 Hz), 8.51 (d, 1H, J= 2.7 Hz), 8.61 (broad s, 1H). Data similar to
the literature.12b
(E)-2-(4-((4-methoxyphenyl)ethynyl)styryl)pyrazine (2a):
Purified by column
chromatography (petroleum ether/EtAcO, 7/3), pale yellow solid. Yield: 43% (134 mg) Mp:
184-186°C. 1H NMR (300MHz, CDCl3) :  3.84 (s, 3H), 6.89 (d, 2H, J = 8.7 Hz), 7.17 (d, 1H,
J = 15.9 Hz), 7.48 (d, 2H, J = 8.7 Hz), 7.52 (d, 2H, J = 8.7 Hz), 7.57 (d, 2H, J = 8.7 Hz), 7.74
(d, 1H, J = 15.9 Hz), 8.41-8.42 (m, 1H), 8.55-8.54 (m, 1H), 8.65-8.64 (m, 1H). 13C NMR and
JMOD (75MHz, CDCl3):  55,3 (CH3), 88.1 (C), 91.1 (C), 114.1 (CH), 115.2 (C), 124.2 (C),
124.5 (CH), 127.2 (CH), 131.8 (CH), 133.1 (CH), 134.5 (CH), 135.5 (C), 142.9 (CH), 143.9
(CH), 144.4 (CH), 151.1 (C), 159.8 (C). HRMS (MALDI), m/z calculated for C21H16N2O
[M]•+ 312.1257 found 312.1267
(E)-2-(4-((4- dimethylaminophenyl)ethynyl)styryl)pyrazine (2b): Purified by column
chromatography (petroleum ether/EtAcO, 1/1), orange solid. Yield: 60% (195 mg) Mp: 177-
179°C. 1H NMR (300MHz, CDCl3) :  3.00 (s, 6H), 6.67 (d, 2H, J = 8.7 Hz), 7.14 (d, 1H, J =
14
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European Journal of Organic Chemistry
10.1002/ejoc.201601204
15.9 Hz), 7.43 (d, 2H, J = 8.7 Hz), 7.52 (d, 2H, J = 8.7 Hz), 7.56 (d, 2H, J = 8.7 Hz), 7.74 (d,
13
1H, J = 15.9 Hz), 8.41-8.42 (m, 1H), 8.55-8.54 (m, 1H), 8.64-8.63 (m, 1H). C NMR and
JMOD (75MHz, CDCl3):  40.1 (CH3), 87.5 (C), 92.6 (C), 109.8 (C), 111.8 (CH), 124.2
(CH), 124.8 (C), 127.2 (CH), 131.6 (CH), 132.8 (CH), 134.6 (CH), 135.0 (C), 142.7 (CH),
143.8 (CH), 144.4 (CH), 150.2 (C), 151.2 (C). HRMS (MALDI), m/z calculated for C22H19N3
[M]•+ 325.1573 found 325.1581
(E)-2-(4-((4- diphenylaminophenyl)ethynyl)styryl)pyrazine (2c): Purified by column
chromatography (petroleum ether/EtAcO, 7/3 to 1/1), orange solid. Yield: 65% (292 mg) Mp:
1
152-154°C. H NMR (300MHz, CDCl3) :  7.07-7.20 (m, 9H), 7.33-7.38 (m, 4H), 7.46 (d,
2H, J = 8.4 Hz), 7.59 (d, 2H, J = 8.5 Hz), 7.64 (d, 2H, J = 8.5 Hz), 7.81 (d, 1H, J = 15.9 Hz),
8.48 (d, 1H, J = 2.7 Hz), 8.91(broad s, 1H), 8.71 (broad s, 1H). 13C NMR and JMOD
(75MHz, CDCl3):  88.6 (C), 91.5 (C), 115.8 (C), 122.2 (CH), 123.6 (CH), 124.2 (C), 124.5
(CH), 125.0 (CH), 127.3 (CH), 129.4 (CH), 131.9 (CH), 132.6 (CH), 134.5 (CH), 135.5 (C),
142.8 (CH), 143.9 (CH), 144.4 (CH), 147.2 (C), 148.1 (C), 151.1 (C). HRMS (MALDI), m/z
calculated for C32H23N3 [M]•+ 449.1886 found 449.1879
(E)-2-(2-(4'-methoxy-[1,1'-biphenyl]-4-yl)vinyl)pyrazine (3a): Purified by column
chromatography (petroleum ether/EtAcO, 7/3), pale yellow solid. Yield: 85% (231 mg) Mp:
207-208°C. 1H NMR (300MHz, CDCl3) :  3.86 (s, 3H), 6.98 (d, 2H, J = 8.7 Hz), 7.17 (d, 1H,
J = 16.2 Hz), 7.57 (d, 2H, J = 8.7 Hz), 7.58 (d, 2H, J = 8.7 Hz), 7.65 (d, 2H, J = 8.7 Hz), 7.76
(d, 1H, J = 16.2 Hz), 8.41 (broad s, 1H), 8.55 (broad s, 1H), 8.66 (broad s, 1H). 13C NMR and
JMOD (75MHz, CDCl3):  55,4 (CH3), 114.3 (CH), 123.6 (CH), 127.0 (CH), 127.8 (CH),
128.0 (CH), 132.9 (C), 134.4 (C), 134.8 (CH), 141.4 (C), 142.6 (CH), 143.8 (CH), 144.4
(CH), 151.4 (C), 159.5 (C). HRMS (MALDI), m/z calculated for C19H18N2O [M + 2H]+
290.1414 found 290.1421
15
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European Journal of Organic Chemistry
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(E)-2-(2-(4'-dimethylamino-[1,1'-biphenyl]-4-yl)vinyl)pyrazine (3b): Purified by column
chromatography (petroleum ether/EtAcO, 7/3 to 1/1), yellow solid. Yield: 73% (220 mg) Mp:
237-238°C. 1H NMR (300MHz, CDCl3) :  3.01 (s, 6H), 6.80 (d, 2H, J = 8.7 Hz), 7.15 (d, 1H,
J = 15.9 Hz), 7.55 (d, 2H, J = 8.7 Hz), 7.60 (d, 2H, J = 8.7 Hz), 7.62 (d, 2H, J = 8.7 Hz), 7.77
(d, 1H, J = 15.9 Hz), 8.39-8.40 (m, 1H), 8.54-8.53 (m, 1H), 8.65-8.64 (m, 1H). 13C NMR and
JMOD (75MHz, CDCl3):  40.5 (CH3), 112.7 (CH), 123.1 (CH), 126.4 (CH), 127.6 (CH),
127.8 (CH), 128.2 (C), 133.7 (C), 135.0 (CH), 141.8 (C), 142.5 (CH), 143.7 (CH), 144.3
(CH), 150.2 (C), 151.5 (C). HRMS (MALDI), m/z calculated for C20H19N3 [M]•+ 301.1573
found 301.1580
(E)-2-(2-(4'-diphenylamino-[1,1'-biphenyl]-4-yl)vinyl)pyrazine (3c): Purified by column
chromatography (petroleum ether/EtAcO, 7/3), yellow solid. Yield: 75% (320 mg) Mp: 194-
1
195°C. H NMR (300MHz, CDCl3) :  7.04 (t, 2H, J = 7.5 Hz), 7.12-7.14 (m, 6H), 7.22 (d,
1H, J = 15.9 Hz), 7.24-7.29 (m, 4H), 7.50 (d, 2H, J = 8.7 Hz), 7.59 (d, 2H, J = 8.7 Hz), 7.64
(d, 2H, J = 8.7 Hz), 7.77 (d, 1H, J = 15.9 Hz), 8.39-8.40 (m, 1H), 8.53 (broad s, 1H), 8.64
(broad s, 1H). 13C NMR and JMOD (75MHz, CDCl3):  113.1 (CH), 127.7 (CH), 124.6 (CH),
126.9 (CH), 127.6 (CH), 127.8 (CH), 129.3 (CH), 134.0 (C), 134.5 (C), 134.8 (CH), 141.2
(C), 142.6 (CH), 143.8 (CH), 144.4 (CH), 147.5 (C), 151.4 (C). HRMS (MALDI), m/z
calculated for C30H23N3 [M]•+ 425.1886 found 425.1884
2-(4-methoxyphenyl)pyrazine (4a): Purified by column chromatography (petroleum
ether/EtAcO, 7/3), cream solid. Yield: 63% (117 mg) Mp: 93-95°C (lit:27 55-56°C). 1H NMR
(300MHz, CDCl3) :  3.89 (s, 3H), 7.04 (d, 2H, J = 8.7 Hz), 8.00 (d, 2H, J = 8.7 Hz), 8.45 (d,
1H, J = 2.7 Hz), 8.59 (broad s, 1H), 8.99 (broad s, 1H). Data similar to the literature.27
2-(4-dimethylaminophenyl)pyrazine (4b): Purified by column chromatography (petroleum
1
ether/EtAcO, 7/3 to 1/1), yellow solid. Yield: 81% (161 mg) Mp: 107-108°C. H NMR
(300MHz, CDCl3) :  3.04 (s, 6H), 6.80 (d, 2H, J = 8.7 Hz), 7.94 (d, 2H, J = 8.7 Hz), 8.33 (d,
16
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European Journal of Organic Chemistry
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13
1H, J = 2.7 Hz), 8.52 (dd, 1H, J1 = 2.7 Hz, J2 = 1.5 Hz), 8.94 (d, 1H, J = 1.5 Hz). C NMR
and JMOD (75MHz, CDCl3):  40.2 (CH3), 112.2 (CH), 128.8 (C), 127.8 (CH), 141.0 (CH),
141.2 (CH), 143.9 (CH), 151.6 (C), 153.1 (C). HRMS (MALDI), m/z calculated for C12H13N3
[M]•+ 199.1104 found 199.1107
2-(4-diphenylaminophenyl)pyrazine (4c): Purified by column chromatography (petroleum
ether/EtAcO, 7/3), yellow solid. Yield: 76% (245 mg). Mp: 85-86°C (lit:28 81-82°C). 1H NMR
(300MHz, CDCl3) :  7.10 (t, 2H, J = 7.2 Hz), 7.20-7.16 (m, 6H), 7.34-7.29 (m, 4H), 7.90 (d,
1H, J = 8.7 Hz), 8.44 (d, 1H, J = 2.7 Hz), 8.59 (dd, 1H, J1 = 2.7 Hz, J2 = 1.5 Hz), 8.99 (d, 1H,
J = 1.5 Hz). Data similar to the literature.28
2-((4-methoxyphenyl)ethynyl)pyrazine (5a): Purified by column chromatography
(petroleum ether/EtAcO, 7/3 to 1/1), yellow solid. Yield: 56% (118 mg) Mp: 60-61°C (lit.29:
55-56°C). 1H NMR (300MHz, CDCl3) :  3.84 (s, 3H), 6.91 (d, 2H, J = 8.7 Hz), 7.56 (d, 2H,
J = 8.7 Hz), 8.45 (d, 1H, J = 2.7 Hz), 8.55 (dd, 1H, J1 = 2.7 Hz, J2 = 1.5 Hz), 8.73 (d, 1H, J =
1.5 Hz). 13C NMR and JMOD (75MHz, CDCl3):  55.4 (CH3), 84.9 (C), 93.8 (C), 113.5 (C),
114.2 (CH), 133.8 (CH), 140.7 (C), 142.4 (CH), 144.4 (CH), 147.6 (CH), 160.7 (C). HRMS
(MALDI), m/z calculated for C13H11N2O [M + H]+ 211.0866 found 211.0872
2-((4-dimethylaminophenyl)ethynyl)pyrazine (5b): Purified by column chromatography
1
(petroleum ether/EtAcO, 7/3), yellow solid. Yield: 76% (170 mg) Mp: 95-97°C. H NMR
(300MHz, CDCl3) :  3.02 (s, 6H), 6.66 (d, 2H, J = 8.7 Hz), 7.49 (d, 2H, J = 8.7 Hz), 8.40 (d,
13
1H, J = 2.7 Hz), 8.52 (dd, 1H, J1 = 2.7 Hz, J2 = 1.5 Hz), 8.70 (d, 1H, J = 1.5 Hz). C NMR
and JMOD (75MHz, CDCl3):  40,1 (CH3), 84.7 (C), 95.7 (C), 107.8 (C), 111.7 (CH), 133.5
(CH), 141.3 (C), 141.7 (CH), 144.2 (CH), 147.4 (CH), 150.9 (C). HRMS (MALDI), m/z
calculated for C14H13N3 [M]•+ 223.1104 found 223.1110
2-((4-diphenylaminophenyl)ethynyl)pyrazine (5c): Purified by column chromatography
1
(petroleum ether/EtAcO, 7/3), yellow solid. Yield: 72% (250 mg) Mp: 107-108°C. H NMR
17
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European Journal of Organic Chemistry
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(300MHz, CDCl3) :  7.02-6.98 (m, 2H), 7.14-7.07 (m, 6H), 7.32-7.27 (m, 4H), 7.44 (d, 2H, J
= 8.7 Hz), 8.44 (d, 1H, J = 2.7 Hz), 8.54 (dd, 1H, J1 = 2.7 Hz, J2 = 1.5 Hz), 8.72 (d, 1H, J =
1.5 Hz). 13C NMR and JMOD (75MHz, CDCl3):  85.3 (C), 94.3 (C), 113.5 (C), 121.3 (CH),
124.1 (CH), 125.5 (CH), 129.5 (CH), 133.2 (CH), 140.8 (C), 142.3 (CH), 144.4 (CH), 146.8
(C), 147.6 (CH), 149.1 (C). HRMS (MALDI), m/z calculated for C24H17N3 [M]•+ 347.1417
found 347.1426
2-(4-((4-methoxyphenyl)ethynyl)phenyl)pyrazine
(6a):
Purified
by
column
chromatography (petroleum ether/EtAcO, 5/5), white solid. Yield: 56% (118 mg) Mp: 162-
163°C. 1H NMR (300MHz, CDCl3) :  3.82 (s, 3H), 6.88 (d, 2H, J = 8.3 Hz), 7.50 (d, 2H, J =
8.3 Hz), 7.64 (d, 2H, J = 8.7 Hz), 8.01(d, 2H, J = 8.7 Hz), 8.50 (broad s, 1H), 8.62 (broad s,
13
1H), 9.04 (broad s, 1H). C NMR and JMOD (75MHz, CDCl3):  55.4 (CH3), 87.9 (C), 91.6
(C), 114.2 (CH), 115.2 (C), 125.5 (C), 126.8 (CH), 132.1 (CH), 133.3 (CH), 135.6 (C), 142.2
(CH), 143.1 (CH), 144.3 (CH), 152.1 (C), 160.0 (C). HRMS (MALDI), m/z calculated for
C19H15N2O [M + H]+ 288.1179 found 288.1186
2-(4-((4-dimethylaminophenyl)ethynyl)phenyl)pyrazine (6b): Purified by column
chromatography (petroleum ether/EtAcO, 7/3), yellow solid. Yield: 62% (185 mg) Mp: 204-
205°C. 1H NMR (300MHz, CDCl3) :  3.00 (s, 3H), 6.67 (d, 2H, J = 9.0 Hz), 7.44 (d, 2H, J =
9.0 Hz), 7.63 (d, 2H, J = 9.0 Hz), 8.00 (d, 2H, J = 9.0 Hz), 8.50 (d, 1H, J = 2.7 Hz), 8.63
(broad s, 1H), 9.04 (d, 1H, J = 1.5 Hz). 13C NMR and JMOD (75MHz, CDCl3):  40.2 (CH3),
87.1 (C), 93.0 (C), 109.7 (C), 111.8 (CH), 126.0 (C), 126.7 (CH), 131.9 (CH), 132.9 (CH),
135.0 (C), 142.1 (CH), 142.9 (CH), 144.2 (CH), 150.3 (C), 152.2 (C). HRMS (MALDI), m/z
calculated for C20H17N3 [M]•+ 299.1417 found 299.1423
2-(4-((4-diphenylaminophenyl)ethynyl)phenyl)pyrazine (6b): Purified by column
chromatography (petroleum ether/EtAcO, 7/3), yellow solid. Yield: 74% (313 mg) Mp: 154-
156°C. 1H NMR (300MHz, CDCl3) :  7.16-7.03 (m, 8H), 7.34-7.28 (m, 4H), 7.42 (d, 2H, J =
18
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European Journal of Organic Chemistry
10.1002/ejoc.201601204
8.7 Hz), 7.67 (d, 2H, J = 8.4 Hz), 8.04 (d, 2H, J = 8.4 Hz), 8.53 (d, 1H, J = 2.7 Hz), 8.66
(broad s, 1H), 9.07 (broad s, 1H). 13C NMR and JMOD (75MHz, CDCl3):  88.3 (C), 91.9
(C), 115.6 (C), 122.1 (CH), 123.7 (CH), 125.1 (CH), 125.4 (C), 126.7 (CH), 129.4 (CH),
132.1 (CH), 132.6 (CH), 135.5 (C), 142.1 (CH), 143.0 (CH), 144.2 (CH), 147.1 (C), 148.2
(C), 152.1 (C). HRMS (MALDI), m/z calculated for C30H21N3 [M]•+ 423.1730 found 423.1728
Acknowledgments
KH thanks the Northern Kentucky University College of Arts & Sciences and Center for
Global Engagement and International Affairs for their financial support to international
mobility.
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