Synthesis and spectroscopic properties of 2,5-bis(benzoazol-2-yl)pyrazines

Article abstract of DOI:10.3987/COM-07-11226

A class of π-conjugated 2,5-bis(benzoazol-2-yl)pyrazine dyes have been synthesized in which 2,5-bis(benzimidazol-2-yl)pyrazine (1) exhibits strong fluorescence in solution. The enhanced fluorescence of 1 with a base leads to future applications such as anion sensing feasible upon chemical modification.

Full text of DOI:10.3987/COM-07-11226

HETEROCYCLES, Vol. 75, No. 3, 2008
531
HETEROCYCLES, Vol. 75, No. 3, 2008, pp. 531 - 536. © The Japan Institute of Heterocyclic Chemistry
Received, 22nd September, 2007, Accepted, 12th November, 2007, Published online, 16th November, 2007. COM-07-11226
SYNTHESIS AND SPECTROSCOPIC PROPERTIES OF 2,5-BIS(BENZO-
AZOL-2-YL)PYRAZINES
Ryota Saito,1,2* Shinnosuke Machida,1 Saori Suzuki,2 and Akira Katoh1
1Department of Materials and Life Science, Seikei University, 3-3-1
Kichijoji-kitamachi, Musashino, Tokyo 180-8633, Japan 2Department of
Chemistry, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba
274-8510, Japan e-mail: saito@chem.sci.toho-u.ac.jp
Abstract – A class of π-conjugated 2,5-bis(benzoazol-2-yl)pyrazine dyes have
been synthesized in which 2,5-bis(benzimidazol-2-yl)pyrazine (1) exhibits strong
fluorescence in solution. The enhanced fluorescence of 1 with a base leads to
future applications such as anion sensing feasible upon chemical modification.
Fluorescent organic molecules continue to arouse strong interest because of their fascinating applications
such as electroluminescent materials,1 molecular probes for clinical uses,2 and molecular sensors for
chemical and biochemical analytes.3 Although there has already been a wide choice of fluorescent
molecules for particular applications, development of organic molecules exhibiting brilliant fluorescence
have still be important because new types of fluorophores have still been desired in the field of
bioimaging, organic electroluminescence, and chromatography.1–3 Our research group has been
interested in the chemistry and fluorescent properties of nitrogen-containing heterocyclic molecules,
especially pyrazines, for many years.4 We have previously studied new luminescent chromophores
based on the pyrazine nucleus, which posses two aromatic substituent on the central pyrazine ring and
exhibit intense fluorescence.4c In continuing efforts to develop brilliant fluorescent compounds based on
aryl-substituted pyrazine chromophores, our interest has focused on introducing benzimidazol and
benzothiazole groups to the pyrazine nucleus, as these benzoazoles are widely found in strong
luminescent
materials
such
as
5’,5’-bis(benzimidazol-2-yl)bipyridine,5
2,6-bis(benzimidazol-2-yl)pyridine,6 and naturally occurring firefly luciferin.7 Herein, we report
synthesis and fluorescent properties of π-conjugated (benzoazol-2-yl)pyrazines (1–3), which are obtained
easily, and one of them, 1, exhibits very strong fluorescence in solution to be reported in this paper for the
first time.

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HETEROCYCLES, Vol. 75, No. 3, 2008
2,5-Bis(benzimidazol-2-yl)pyrazine (1)8 was prepared by reacting 2,5-pyrazinedicarboxylic acid,
prepared by oxidation of 2,5-dimethylpyrazine,9 with two equimolar of phenylenediamine in
polyphosphoric acid (PPA) as shown in Scheme 1. Fluorescent (benzimidazol-2-yl)pyrazine (2)10 was
also obtained as a by-product, indicating decarboxylation occurred during the reaction under such a high
temperature condition. This side reaction substantially reduced the yield of the desired compound.
2,5-Bis(benzothiazol-2-yl)pyrazine (3)11 was prepared in the same manner with 2-aminobenzenethiol (5)
as shown in Scheme 1. In this case, multiple by-products were detected by TLC analysis and were hard
to be isolated. Only 3 was isolated by repeated column chromatography on silica gel.
NH2
NH2
PPA
H
N
N
CH3
N
N
CO2H
N
N
N
N
N
H2SeO3
+
pyridine-water
N
H
N
N
N
H
N
H3C
HO2C
185 °C, 65 h
1
2
NH2
SH
N
N
S
S
N
PPA
220 °C, 31 h
N
3
Scheme 1
The absorption spectra of obtained 1–3 were measured in dimethyl sulfoxide (DMSO) at room
temperature under aerated condition. The results are presented in Figure 1 and Table 1. The absorption
bands of 1 were observed at 395 (shoulder), 378 and 325 nm (shoulder). By comparison of the
absorption spectrum of 2, it is found that the longer peaks attribute to the absorption of the whole
molecule 1, while the shorter peak corresponds to the partial electron transition of the
(benzimidazol-2-yl)pyrazine moiety. Similar result was obtained when the absorption of 3 was
measured as shown in Figure 1.
Fluorescence spectra of 1–3 in DMSO at room temperature under aerated condition are shown in Figure 2,
and the data are listed in Table 1, accompanied by fluorescence quantum yields determined relative to
quinine sulfate in 0.1 mol L–1 sulfuric acid (Φ = 0.55, excited at 366 nm). The dye 1 exhibited blue
emission band at λFL = 444 nm, which is longer than that of 2 at λFL = 378 nm as expected from the
Table 1. Absorption and Fluorescence Data of Benzoazolylpyrazines 1–3
fluorescence
quantum yield, Φ
Compound
solvent
λ
abs /nm (ε /dm3M–1cm–1)
λFL /nm
395 (sh 34000), 378 (37800),
325 (sh 18800)
1
DMSO
444
477
0.90
DMSO containing
NaOMe
412 (36800), 336 (15400)
1.0
2
3
DMSO
DMSO
327 (19000)
394 (sh 245009), 375 (29900)
378
447
0.29
0.009

HETEROCYCLES, Vol. 75, No. 3, 2008
533
0.4
0.3
0.2
0.1
0
(+ NaOMe)
1
1
1
3
2 (x5)
2
3 (x100)
350
400
450
500
550
250
300
350
Wavelength /nm
400
450
500
Wavelength /nm
Figure 1. Absorption spectra of 1 (solid line), 2
(dash-dotted line), and 3 (broken line) in DMSO; c =
1.0 x 10–5 M
Figure 2. Fluorescence spectra (corrected) of 1 (thick
solid line), 2 (dash-dotted line) and 3 (broken line) in
DMSO and 1 in DMSO containing 5% (v/v) of 1 M
NaOMe in methanol (thin solid line); c = 2.0 x 10–7 M
expanded π-conjugation.
The striking result is that the dye 1 exhibits strong blue fluorescence with high fluorescence quantum
yield (Φ1 = 0.90). The emission profile of 3 was similar to that of 1, except the fluorescence quantum
yield, Φ3 = 0.009, is much lower than that of 1.12
In order to get information about the physicochemical property of 1, the optimized structure and the
energy levels of HOMO and LUMO were estimated by the AM1 method.13 For comparison, those
properties of 2 and 3 were also calculated, and the results are listed in Table 2. For each compound, the
pyrazine nitrogen and the imine nitrogen of the benzoazole unit prefer to be in the s-trans configuration
each other rather than in the s-cis probably due to the electronic repulsion between the lone pairs on the
sp2 nitrogen atoms, according to the calculation. The conformations of 1 and 2 were estimated to be
almost planar, while that of 3 was found to slightly twist (Table 1). The deviation from the planar in 3 is
possibly attributable to the avoidance of the dipole-dipole repulsion caused by the lone pairs on the
Table 2. AM1-calculated dihedral angle between pyrazine ring and benzoazole, heat of formation (in
kcal･mol-1), dipole moment in the ground state (µ in Debye), HOMO and LUMO energy levels (in eV),
and differential energy (∆E in eV) between the HOMO and LUMO of 2,5-bis(benzimidazol-2-yl)-
pyrazine (1), 2-(benzimidazol-2-yl)pyrazine (2), and 2,5-bis(benzothiazol-2-yl)pyrazine (3)
Heat of
Dihedral
angle
Compound
formation
/kcal•mol-1
185.8
HOMO /eV LUMO /eV
µ /D
∆E /eV
1
2
3
0.3°
0.3°
0.06
2.95
0.11
-8.720
-8.867
-9.172
-1.455
-0.997
-1.754
7.265
7.870
7.418
115.1
28.5, 30.4°
146.9

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HETEROCYCLES, Vol. 75, No. 3, 2008
pyrazine nitrogen and on the sulfur. To confirm these estimations X-ray crystal analysis of these
compounds should be performed, but it has not been completed because single crystals of these
compounds suitable for the analysis have been hardly obtained. The HOMO-LUMO gap (∆E) for 1 was
smaller than that for 2 as expected, showing good agreement with the difference in the experimentally
observed 0-0 bands for 1 and 2. Figure 3 depicts frontier molecular orbitals for 1–3. For each
compound, the HOMO coefficients are mainly distributed over the benzoazole moiety and the LUMO
coefficients are localized on the pyrazine ring. From these results, the lowest-energy (0-0) transition for
all dyes can be assignable as charge-transfer transition from benzoazole moiety to the π* orbital of the
pyrazine ring. At this point, the charge transfer would occur from one side for 2, giving large transition
moment, while the transition would occur from each side of the pyrazine for 1, giving almost symmetric
moment. Figure 4 exhibits the optimized structure of 1 and 3 in the excited states calculated by the
AM1 method, and both of them are estimated to take planar conformation in the excited states. These
simulations suggest that the dye 1 does not change its conformation upon excitation, while the rotation of
the aryl groups may occur in 3 in the excited state. Thus, it is conceivable that the planer π-conjugated
structure and the symmetrical transition moment of 1 cause the efficient fluorescence emission like other
strong fluorescent π-conjugated dyes.14 Although the reason that accounts for the weak fluorescence of
3 is still unclear at present, the nonradiative deactivation such as free rotations and/or the S1-T1
intersystem crossing could cause the decreased fluorescence efficiency of 3.
It is worth noting that the fluorescence of 1 exhibited bathochromic shift (thin solid line in Figure 1) and
the fluorescence quantum yield was enhanced (Φ1+base ~ 1) when 1 was dissolved in DMSO containing
sodium methoxide (0.05 M). The NH units are known to interact strongly with anion.15 Under this
condition, the NH moiety of the 2-benzimidazolyl group could interact with methoxide anion to increase
A
B
C
LUMO
HOMO
LUMO
HOMO
LUMO
HOMO
Figure 3. Frontier molecular orbitals (HOMO and LUMO) for 1 (A), 2 (B) and 3 (C) calculated by the
AM1-COSMO method.

HETEROCYCLES, Vol. 75, No. 3, 2008
535
A
B
Top view
Side view
Top view
Side view
Figure 4. Computer-simulated optimized geometries of 1 (A) and 3 (B) in the first excited states
estimated by the AM1 method
the electron donating character of the 2-benzimidazolyl moiety, possibly being connected with the high
fluorescent efficiency.
In conclusion, we have succeeded in developing the intensely blue-fluorescent pyrazine dye 1, whose
quantum efficiency was found to as high as 0.90. The anomalously high fluorescence quantum yield of
1 accompanied by the spectral shift in the presence of the anion may provide this fluorescent dye
potentially superior to conventional fluorometric anion sensors. Since derivatization of 1 can be attained
by replacing the starting phenylenediamine with its derivatives and introducing substituents on the NH,
we may say that we have established structural groundwork to aid in the further design of new
fluorophores applicable in various areas. Further studies, including derivatization of 1, are underway in
our research group.
ACKNOWLEDGEMENTS
This work was partially supported by “High-Tech Research Center” Project for Private Universities:
matching fund subsidy from MEXT (2004-2008). Financial support to R.S. by the Faculty of Science
Special Grant for Promoting Scientific Research at Toho University is also gratefully appreciated.
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