Synthesis and fluorescence properties of difluoro[amidopyrazinato-O,N]boron derivatives: a new boron-containing fluorophore

Article abstract of DOI:10.1016/j.tetlet.2010.01.072

New boron-containing fluorophores, difluoro[amidopyrazinato-O,N]boron (APB) derivatives, were prepared from amidopyrazines. The fluorescence properties of APB were successfully modulated by an aryl substitution at the C8 position.

Full text of DOI:10.1016/j.tetlet.2010.01.072

Tetrahedron Letters 51 (2010) 1613–1615
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis and fluorescence properties of difluoro[amidopyrazinato-O,N]boron
derivatives: a new boron-containing fluorophore
a
a
b
a
a
a,*
Sojiro Hachiya , Takayuki Inagaki , Daisuke Hashizume , Shojiro Maki , Haruki Niwa , Takashi Hirano
a
Department of Applied Physics and Chemistry, The University of Electro-Communications, Chofu, Tokyo 182-8585, Japan
Advanced Technology Support Division, RIKEN, Wako, Saitama 351-0198, Japan
b
a r t i c l e i n f o
a b s t r a c t
Article history:
New boron-containing fluorophores, difluoro[amidopyrazinato-O,N]boron (APB) derivatives, were pre-
pared from amidopyrazines. The fluorescence properties of APB were successfully modulated by an aryl
substitution at the C8 position.
Received 22 December 2009
Revised 18 January 2010
Accepted 22 January 2010
Available online 28 January 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Cypridina oxyluciferin (Scheme 1) and coelenteramide are the
light-emitter compounds for bioluminescence of the ostracod Cyp-
of 2a shows a bond length alternation (Fig. 1B). Unfortunately,
however, APBs (2) were slowly decomposed to give 1 by solvolysis
in a protic solvent such as methanol.
1
2
ridina and the jellyfish Aequorea, respectively. These light-emitter
compounds have an amidopyrazine core structure. We investigated
the fluorescence properties of the derivatives of Cypridina oxyluci-
ferin and coelenteramide and found that the excited singlet states
of these compounds have an intramolecular charge transfer (ICT)
UV–vis absorption and fluorescence spectra of the APB deriva-
tives (2) were measured in cyclohexane, chloroform, and acetoni-
8
,9
trile.
It was confirmed that the excitation spectra of the
fluorescence agree with the corresponding absorption spectra.
The spectral data are summarized in Table 1. Figure 2 shows repre-
sentative spectra in chloroform. The lowest energy absorption
bands of 2a and 2c in chloroform were observed at 331 and
353 nm, respectively, and fluorescence emission maxima (k ) of
f
2a and 2c were observed at 384 and 402 nm with quantum yields
3
character and show fluorescence solvatochromism. Because fluo-
rescent compounds are widely used in many applications, such as
fluorescent sensors for biological imaging and light-emitting com-
ponents for organic light-emitting devices,4 one of our goals is to
design a new fluorescent compound based on Cypridina oxyluci-
ferin and coelenteramide. We attempted to modify the chemical
structure of amidopyrazine using the methodology for preparing
boron dipyrromethene (BODIPY).5 We then successfully prepared
new boron-containing fluorophores, difluoro[amidopyrazinato-
O,N]boron (APB) derivatives (2), by the reactions of amidopyrazines
O
N
N
NH
(
1) with BF
and fluorescence properties of these APB derivatives 2.
Pivalamidopyrazine 1a was treated with BF O in the pres-
3
(Scheme 1). In this Letter, we describe the synthesis
NH
NH2
NH
ÁEt
3 2
ence of N,N-diisopropylethylamine (DIPEA) at room temperature
N
H
to give 8-t-butyl APB (2a) in 83% yield.6 Although acetamidopyr-
Cypridina oxyluciferin
azine 1b also reacted with BF
3
ÁEt
2
O in the presence of DIPEA, we
could not isolate 2b from the complex mixture of products. This re-
sult suggests that deprotonation of the methyl group at C8 induces
decomposition of 2b. Therefore, it would be preferable to use an
amidopyrazine having a tertiary or aryl group at C8 for preparing
APB compounds. We were also able to convert benzamidopyrazine
O
R
F
O
8
R
F
B
N
1
N
N
NH
BF ·Et O
N7
3
2
6
5
2
3
DIPEA, CH2Cl2
RT
N
1
c and its derivatives 1d and 1e to the corresponding APBs 2c–e in
4
4
0À60% yields. Crystal structure analysis of 2a confirmed its APB
1
a: R = C(CH )
2a (83%)
2b (---)
3
3
7
skeleton (Fig. 1A). The boron-containing ring is slightly distorted
1b: R = CH
1c: R = Ph
3
by the introduction of the sp3 boron atom. The core bicyclic ring
2c (56%)
2d (41%)
2e (43%)
1
1
d: R = C H CN
6 4
e: R = C H OCH
3
6
4
*
Corresponding author. Tel.: +81 42 443 5489; fax: +81 42 486 1966.
E-mail address: hirano@pc.uec.ac.jp (T. Hirano).
Scheme 1. Structure of Cypridina oxyluciferin and synthesis of APB 2.
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.01.072

1
614
S. Hachiya et al. / Tetrahedron Letters 51 (2010) 1613–1615
f
(U ) to be 0.12 and 0.15, respectively. This result indicates that the
introduction of a phenyl group instead of a tert-butyl group at C8
Aside view
induces 20 nm red shifts of the lowest energy absorption and fluo-
rescence emission bands. Thus, the expansion of the
p-electronic
conjugation at C8 of the APB skeleton effectively modulates the
spectroscopic characteristics. Another phenyl substitution effect
appears to be an increase of the extinction coefficient of the lowest
energy absorption band compared to that of 2a. The absorption
top view
maxima (kab) and the k
dependency on solvent polarity, whereas the
acetonitrile and that of 2d were less than 0.01. On the other hand,
-methoxyphenyl derivative 2e showed fluorescence solvatochro-
f
values of 2a, 2c, and 2d indicate a slight
1
0
f
U value of 2c in
4
mism (Fig. 3). Although the lowest energy absorption bands of 2e
showed a small solvent-dependent variation at around 370 nm,
the k
f
value of 2e was red shifted with increased solvent polarity.10
This result indicates that the ICT character of the excited singlet
state of 2e is much greater than that of the ground state.
To better understand the observed structural and spectroscopic
properties of the APB derivatives (2), DFT and time-dependent (TD)
B
F
1
.456
O
C(CH3)3
1.293
DFT calculations on 2 and amidopyrazines 1a and 1c were con-
F
B
N
11–14
ducted at the B3LYP/6-31G(d) level (Table 2).
Optimized struc-
1.581
N
ture of 2a was very similar to the X-ray crystal structure of 2a,
whose boron-containing ring is bent. The HOMO and LUMO levels
of 2a and 2c were lower than those of 1a and 1c, indicating that the
electron-accepting character of the APB derivative is greater than
that of the corresponding amidopyrazine. Although the excitation
wavelengths (kex) calculated for 2 were predicted to be shorter
than their kab values observed in cyclohexane, the relative differ-
ences in the kex and kab values among 2a and 2c–e agree well with
each other. The finding that the oscillator strength (f) of 2c is great-
1
.353
1.369
1.371
1.411
1.348
N 1.318
Figure 1. Molecular structure of 2a (A) with the atomic displacements drawn at the
0% probability level and selected bond distances in a partial structure of 2a (B).
5
er than that of 2a also matches the difference in the e values of the
Table 1
lowest energy absorption bands of 2a and 2c. Figure 4 shows the
electron distribution of the HOMOs and LUMOs of 2c and 2e. While
the HOMO and LUMO densities of 2c are located on the APB skel-
eton, the HOMO and LUMO densities of 2e are mainly localized
on the 4-methoxyphenyl moiety and the APB skeleton, respec-
tively. This result supports the premise that the excited singlet
Electronic absorption and fluorescence of 2a and 2c–e in various solvents at 25 °C
Compound Solvent
k
ab/nm (
e
/104)a
f f
k /nm (U
)b
2
2
2
2
a
C
CHCl
CH
6
H
12
332 (0.86)
331 (1.1)
329 (0.88)
384 (0.078)
384 (0.12)
386 (0.10)
3
3
CN
c
C
CHCl
CH
6
H
12
351 (2.6), 274 (1.7)
353 (2.7), 274 (1.7)
349 (2.7), 268 (1.7)
398 (0.18)
402 (0.15)
395 (0.008)
3
3
CN
d
e
C
CHCl
CH
6
H
12
351 (2.0), 271 (1.4)
354 (2.1), 271 (1.4)
351 (2.0), 266 (1.4)
404 (0.013)
408 (0.004)
n.d.c
a
A3
.0
.0
.0
B
a
b
c
3
1.0
0.5
0.0
3
CN
c
C
6
H
12
382 (3.0), 365 (3.2), 298 (1.2), 281
411, 396
(0.29)
429 (0.16)
478 (0.062)
2
b
(1.2)
CHCl
CH CN
3
373 (2.9), 286 (1.1)
363 (2.9), 291 (1.1)
ε
3
1
a
b
c
in dm3 mol cm ).
À1
À1
Absorption maximum (kab) and extinction coefficient (
Fluorescence emission maximum (k
Fluorescence was weak.
e
f
) and quantum yield ( ).
U
f
0.0
3
00
400
400
500
600
wavelength / nm
wavelength / nm
Figure 3. UV–vis absorption spectra (A) and fluorescence spectra (B) of 2e in
cyclohexane (a), chloroform (b), and acetonitrile (c) at 25 °C.
B
A3
.0
.0
.0
.0
d
a b
d
c
1.0
b
c
Table 2
2
HOMO and LUMO and vertical wavelengths (kex) and oscillator strengths (f) for the
allowed transitions to the excited singlet states with the lowest excitation energies
for 1 and 2 obtained by DFT and TDDFT calculations at the B3LYP/6-31G(d) level
0
.5
ε
1
a
Compound
HOMO/eV
LUMO/eV
k
ex/nm
f
1a
1c
2a
2c
2d
2e
À6.41
À6.55
À7.14
À6.76
À7.15
À6.24
À1.31
À1.50
À2.58
À2.64
À3.08
À2.47
263
271
301
333
334
363
0.12
0.28
0.18
0.42
0.62
0.44
0
0.0
300
400
400
500
600
wavelength / nm
wavelength / nm
Figure 2. UV–vis absorption spectra (A) and fluorescence spectra (B) of 2a (a), 2c
b), 2d (c), and 2e (d) in chloroform at 25 °C.
(

S. Hachiya et al. / Tetrahedron Letters 51 (2010) 1613–1615
1615
T.; Fukatsu, H. Tetrahedron Lett. 1969, 4299–4302; (d) Shimomura, O.; Johnson,
F. H.; Masugi, T. Nature 1969, 164, 1299–1300.
2
.
.
(a) Shimomura, O.; Johnson, F. H. Nature 1970, 227, 1356–1357; (b)
Shimomura, O.; Johnson, F. H. Tetrahedron Lett. 1973, 2963–2966.
(a) Saito, R.; Hirano, T.; Niwa, H.; Ohashi, M. J. Chem. Soc., Perkin Trans. 2 1997,
3
1711–1716; (b) Imai, Y.; Shibata, T.; Maki, S.; Niwa, H.; Ohashi, M.; Hirano, T. J.
Photochem. Photobiol. A 2001, 146, 95–107; (c) Mori, K.; Maki, S.; Niwa, H.;
Ikeda, H.; Hirano, T. Tetrahedron 2006, 62, 6272–6288; (d) Hirano, T.;
Takahashi, Y.; Kondo, H.; Maki, S.; Kojima, S.; Ikeda, H.; Niwa, H. Photochem.
Photobiol. Sci. 2008, 7, 197–207.
4.
Textbooks: (a) Tsien, R. Y. In Fluorescent Chemosensors for Ion and Molecule
Recognition; Czarnik, A. W., Ed.; ACS: Washington, DC, 1993; pp 130–146; (b)
Bamfield, P. Chromic Phenomena—Technological Applications of Colour Chemistry;
RSC: Cambridge, 2001; (c) Zollinger, H. Color Chemistry: Syntheses, Properties,
and Applications of Organic Dyes and Pigments, 3rd ed.; Wiley-VCH: Weinheim,
LUMO (2c)
LUMO (2e)
2003; (d) Industrial Dyes: Chemistry, Properties, Applications; Hunger, K., Ed.;
Wiley-VCH: Weinheim, 2003.
5
.
.
(a) Treibs, A.; Kreuzer, F.-H. Justus Liebigs Ann. Chem. 1968, 718, 208–223; (b)
Loudet, A.; Burgess, K. Chem. Rev. 2007, 107, 4891–4932; (c) Ziessel, R.; Ulrich,
G.; Harriman, A. New J. Chem. 2007, 31, 496–501; (d) Ulrich, G.; Ziessel, R.;
Harriman, A. Angew. Chem., Int. Ed. 2008, 47, 1184–1201.
6
To
diisopropylethylamine (0.14 mL, 0.76 mmol) and BF
.13 mmol) were added at room temperature under Ar, and the reaction
mixture was stirred over night. The reaction mixture was concentrated in
a
solution of 1a (102 mg, 0.57 mmol) in dichloromethane (0.5 mL),
3
ÁEt (0.16 mL,
2
O
1
HOMO (2c)
HOMO (2e)
2
vacuo, and the residue was purified by column chromatography (SiO ,
chloroform/ethyl acetate) to give 2a (108 mg, 83%) as colorless cubes.
Figure 4. Frontier orbitals of 2c and 2e obtained by DFT calculations at the B3LYP/
-31G(d) level.
7. Single crystals of 2a were obtained by recrystallization from hexane.
Diffraction data were collected with a Rigaku AFCÀ8 CCD diffractometer
6
using multi-layer confocal-mirror monochromated and focused MoK
a
radiation (k = 0.71073 Å) at 90 K. The structure was solved by direct methods
using the program SIR-2004 [Burla, M. C.; Caliandro, R.; Camalli, M.; Carrozzini,
B.; Cascarano, G. L.; De Caro, L.; Giacovazzo, C.; Polidori, G.; Spagna, R., J. Appl.
Crystallogr. 2005, 38, 381À388.]. Refinements were carried out by a least-
squares method on F2 using the program SHELXL-97 [Sheldrick, G. M. Acta
Crystallogr. Sect. A, 2008, 64, 112–122]. Crystal data are as follows:
state of 2e exhibits charge transfer from the 4-methoxyphenyl
moiety to the APB skeleton.
In conclusion, we successfully prepared a new boron-containing
fluorophore, APB 2, by applying the conventional method for pre-
paring BODIPY to amidopyrazine 1. APB 2 is more fluorescent than
the corresponding precursor 1, and the fluorescence property of 2
was modulated by a substituent at C8. In particular, 4-methoxy-
phenyl derivative 2e showed fluorescence solvatochromism. Fur-
ther studies to reveal the redox property of APB and to modify
APB for finding new light-emitting characters are now in progress.
C
9
H
12BF
2
N O, M = 227.03, tetragonal, space group I4 /a, a = 16.380(2),
3
1
3
À3
À1
c = 16.240(3) Å, V = 4357.3(11) Å , Z = 16, D = 1.384 Mg m
x
,
l
= 0.115 mm
199 unique data, final R(F) = 0.0390, wR(F ) = 0.0976 for 2827 observed data
I > 2 (I)]. The crystallographic data have been deposited at the CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK (CCDC 755766).
,
2
3
[
r
À5
8. Concentrations of
2
were 1.0–5.0 Â 10
M
for UV–vis absorption
À6
measurements and 1.0–5.0 Â 10 M for fluorescence measurements.
The authors thank a referee who pointed out that the data of excited state
lifetime will increase the impact of this work. We unfortunately cannot obtain
the data soon, because we do not have an instrument for fluorescence lifetime
measurement. We would like to measure the data for preparing a full paper.
9
.
Acknowledgment
1
0. Reichardt, C. Solvents and Solvent Effects in Organic Chemistry, 3rd ed.; Wiley-
VCH: Weinheim, 2003.
We acknowledge technical assistances of computation for
quantum chemical calculations from the Information Technology
Center of UEC.
11. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken,
V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A.
J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G.
A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.;
Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.;
Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.;
Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe,
M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.
GAUSSIAN 03, Revision C.02; Gaussian: Wallingford, CT, 2004.
Supplementary data
Supplementary data (general experimental, synthesis of 1,
physical data of 2, and DFT calculation data) associated with this
article can be found, in the online version, at doi:10.1016/
j.tetlet.2010.01.072.
References and notes
1
1
2. Becke, A. D. J. Chem. Phys. 1993, 98, 5648–5652.
3. Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785–789.
1
.
(a) Goto, T. Pure Appl. Chem. 1968, 17, 421–441; (b) Goto, T.; Inoue, S.; Sugiura,
S.; Nishikawa, K.; Isobe, M.; Abe, Y. Tetrahedron Lett. 1968, 4035–4038; (c) Goto,
14. Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J. J. Phys. Chem. 1994,
98, 11623–11627.