π-Sufficient heteroaromatic compounds fused naphthalimide unit as novel solvatochromic fluorophores

Article abstract of DOI:10.1016/j.tetlet.2011.08.066

The carbazoles 1 and dibenzofurans 2 having naphthalimide unit were synthesized by the cross coupling reaction of 4-bromonaphthalimide 3 with aniline and phenol derivatives followed by the intramolecular cyclization, respectively. The chromophores 1c and

Full text of DOI:10.1016/j.tetlet.2011.08.066

Tetrahedron Letters 52 (2011) 5494–5496
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Tetrahedron Letters
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p-Sufficient heteroaromatic compounds fused naphthalimide unit as novel
solvatochromic fluorophores
⇑
Rui Umeda, Hiroaki Nishida, Motohiro Otono, Yutaka Nishiyama
Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Yamate-cho, Suita, Osaka 564 8680, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The carbazoles 1 and dibenzofurans 2 having naphthalimide unit were synthesized by the cross coupling
reaction of 4-bromonaphthalimide 3 with aniline and phenol derivatives followed by the intramolecular
cyclization, respectively. The chromophores 1c and 2c substituted methoxy group exhibited the strong
fluorescence solvatochromism.
Received 12 July 2011
Revised 10 August 2011
Accepted 11 August 2011
Available online 2 September 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Solvatochromic
Fluorescent
Carbazoles
Dibenzofurans
Naphthalimide
Solvatochromism is the ability of chromophores to change their
solution colors depending on the environmental conditions, such
as solvent polarity. Especially, fluorescence solvatochromic dyes
are of great interest, because they have potential applications as
environment-sensitive fluorescent probes in biological fields.1 The
compounds, which incorporate both electron-donating and elec-
H
N
O
O
O
N
R2
N
R2
O
R1
O
R1
2
1
tron-accepting groups linked by p-conjugated cores, are promising
candidates of solvatochromic fluorophores owing to their inherent
dipole moments. 2-Propionyl-6-dimethylaminonaphthalene (PRO-
DAN), 4-dimethylamino phthalimide (4-DMAP), and 4-amino-1,8-
naphthalimide derivatives are commonly used as solvatochromic
fluorophores. It is presumed that the damage on biological targets,
such as proteins and living cells, can be caused by short-wavelength
irradiation light. Thus, the desired properties of this class of com-
pounds are high extinction coefficient, less inhibition of structural
and dynamical information of targets, and excitation at visible light
region. Moreover, to develop a large library of valuable fluorescence
solvatochromic dyes, it is preferable that these compounds with var-
ious functional groups must be easily synthesized.
The synthesis of carbazoles 1 and dibenzofurans 2 is shown in
Schemes 1 and 2 (see SI for details). Palladium-catalyzed coupling
Br
NH2
R
H
N
O
a)
N
N
O
O
O
R
4a (R = H)
4b (R = CN)
4c (R = OCH3)
3
To this end, we designed
p-sufficient heteroaromatic com-
H
N
O
b)
pounds, indole and benzofuran, fused naphthalimide unit 1 and
2. It is expected that these chromophores 1 and 2 would have fully
planar conformation and large dipole moment due to containing
both the electron-donating and electron-accepting units. Herein,
we report the synthesis and preliminary photophysical character-
ization of heteroaromatic compounds fused naphthalimide unit 1
and 2.
N
O
R
1a (R = H)
1b (R = CN)
1c (R = OCH3)
Scheme 1. Ragents and conditions: (a) Pd(OAc)2, DPEPhos, t-BuONa, toluene, room
temperature; yield: 94% for 4a (R = H), 91% for 4b (R = CN), 95% for 4c (R = OCH3);
(b) Pd(OAc)2, K2CO3, t-BuCOOH, air, 130 °C; yield: 44% for 1a (R = H), 10% for 1b
(R = CN), 14% for 1c (R = OCH3).
⇑
Corresponding author.
E-mail address: nishiya@kansai-u.ac.jp (Y. Nishiyama).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.08.066

R. Umeda et al. / Tetrahedron Letters 52 (2011) 5494–5496
5495
reaction2 of 4-bromonaphthalimide 3 with aniline derivatives pro-
Br
ceeded smoothly even at room temperature to give diarylamines 4
in excellent yields. Continuously, the palladium-catalyzed intra-
molecular cyclization of 4 in pivalic acid as solvent under air3 gave
the corresponding carbazoles 1 (Scheme 1).
The diarylethers 5a (R = H) and 5c (R = OCH3) were synthesized
by Cu(I)-catalyzed coupling reaction4 of 3 with the corresponding
phenols in good yields. In the case of 4-cyanophenol, the yield of
diaryether 5c (R = CN) was quite low (<5% yield), however, the yield
of 5c was remarkably increased by using CuBr2 instead of Cu(I) as a
catalyst. Pd(II)-catalyzed intramolecular cyclization of the diaryle-
thers 5 did not proceed under the same conditions as that of 4, how-
ever, in the co-existence of Cu(OAc)2, intramolecular cyclization of
5 gave dibenzofurans 2 in 39–91% yields (Scheme 2).5
As a preliminary study of photophysical properties, we mea-
sured UV–vis and FL spectroscopy of carbazoles 1 and dibenzofu-
rans 2 in various solvents. In spite of the fact that 1 and 2 were
extended by indole and benzofuran units, their absorbance max-
ima were similar to those of the 4-amino- and 4-hydroxy-1,8-
naphthalimide derivatives (Table 1 and Table S1, SI).6 Although
FL spectrum of 1a,b and 2a,b showed relatively weak solvatochro-
mic shift (Table S1, SI), those of 1c and 2c substituted methoxy
group exhibited the strong fluorescence solvatochromism (Fig. 1)
and the color changes of 1c and 2c were visualized in different sol-
OH
R
O
O
a) or b)
N
N
O
O
O
R
5a (R = H)
5b (R = CN)
5c (R = OCH3)
3
O
O
c)
N
O
R
2a (R = H)
2b (R = CN)
2c (R = OCH3)
Scheme 2. Reagents and conditions: (a) R = H and OCH3: CuI, 1-butylimidazole,
K2CO3, toluene, reflux; yield: 99% for 5a (R = H), 94% for 5c (R = OCH3). (b) R = CN:
CuBr2, Cs2CO3, DMF, 120 °C; yield: 53% for 5b (R = CN). (c) Pd(OAc)2, Cu(OAc)2, t-
BuCOOH, air, 130 °C; yield: 63% for 2a (R = H), 39% for 2b (R = CN), 91% for 2c
(R = OCH3).
vents (Fig. 2). The results of photophysical properties of carbazole
1c and dibenzofuran 2c are shown in Table 1.
Table 1
Photophysical properties of 1c (R = OCH3) and 2c (R = OCH3) in different solvents
Compound
Solvent
Dielectric constant
Absorptiona
Fluorescencea
kabs (nm)
e
(MÀ1 cmÀ1
)
kem (nm)
Ub
1c
Toluene
CH2Cl2
Acetonitrile
DMSO
2.38
8.93
36.6
46.7
398
409
409
419
10,400
14,100
15,000
15,200
464
514
540
545
0.46
0.25
0.08
0.08
2c
Toluene
CH2Cl2
Acetonitrile
DMSO
2.38
8.93
36.6
46.7
358
361
359
363
8,600
12,200
12,200
12,800
436
494
530
547
0.21
0.15
0.03
0.01
a
[c] = ꢀ10À5 M.
b
Absolute quantum yield measured by using an integrating sphere.
Figure 1. (a) UV–vis absorption and (b) fluorescence spectra of 1c (R = OCH3) and (c) UV–vis absorption and (d) fluorescence spectra of 2c (R = OCH3) in different solvents.

5496
R. Umeda et al. / Tetrahedron Letters 52 (2011) 5494–5496
more polar forms such as zwitterionic species. The plausible mes-
omeric ionic forms in 1c and 2c are shown in Scheme 3.7
In conclusion, we succeeded in the synthesis of carbazoles 1 and
dibenzofurans 2 having naphthalimide unit. In particular, 1c and
2c having methoxy group showed large fluorescence solvatochro-
mic shifts. The compounds 1 and 2 can be easily prepared from
commercially available materials in three steps and various sub-
stituents would be introduced at not only the N-position of naph-
thalimide moiety but also at the carbazole and dibenzofuran rings.
These results clearly show that compounds having these structures
are very hopeful candidates for environment-sensitive fluorescent
probes. Further investigation of the effect of substituents in 1 and 2
is currently in progress.
Figure 2. Color changes of 1c (R = OCH3) (left) and 2c (R = OCH3) (right) in different
solvents.
Acknowledgments
O
O
X
X
This research was supported by a Grant-in-Aid for Science Re-
search, and Strategic Project to Support the Formation of Research
Bases at Private Universities from the Ministry of Education, Cul-
ture Sports, Science and Technology of Japan.
N
N
N
Ar
Ar
O
O
O
OCH3
1c: X = NH, 2c: X = O
OCH3
Supplementary data
O
X
O
X
Supplementary data (complete experimental details and char-
acterization data, 1H and 13C NMR spectra, additional UV–vis spec-
tra and fluorescence spectra) associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2011.08.066.
N
N
Ar
Ar
O
O
OCH3
OCH3
References and notes
O
X
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Ar
OCH3
Scheme 3. Plausible mesomeric ionic forms in 1c and 2c.
Fluorescence emission spectra of 1c are strongly dependent on
the polarity of the solvent: the maximum emission wavelength is
red-shifted almost 80 nm from 464 nm in toluene to 545 nm in
DMSO, and the fluorescence quantum yield decreases more than
6 times from toluene (0.46) to DMSO (0.08). In the case of 2c, larger
solvatochromic shift (ca. 110 nm) was observed from 436 nm in
toluene to 547 nm in DMSO. However, the fluorescence quantum
yields of 2c were lower than those of 1c.
In principle, fluorescence solvatochromic shifts are caused by a
change in the energy gap between ground state and excited state of
different polarities. The chromophores 1 and 2 should adopt simi-
lar conformations in both ground states and excited states because
of rigid structures of them. The dipole moments of excited states of
1c and 2c having methoxy group are larger than those of 1a,b and
2a,b. We, therefore, assumed that the increasing solvent polarity
led to the stabilization of excited states of 1c and 2c which have
7. The delocalization structures of the 4-amino-1,8-naphthalimides conjugated
with the carbonyl groups has been proposed, see: (a) Peters, A.; Bide, M. Dyes
and Pigments 1985, 6, 349–375; (b) Philipova, T.; Karamancheva, I.; Grabchev, I.
Dyes and Pigments 1995, 28, 91–99; (c) Karamancheva, I.; Tadjer, A.; Philipova,
T.; Madjarova, G.; Ivanova, C.; Grozeva, T. Dyes and Pigments 1998, 36, 273–285.