β- Thiophene-Fused BF2-Azadipyrromethenes as Near-Infrared Dyes

Article abstract of DOI:10.1021/ol4034622

A facile synthetic route to a new class of near-IR β-thiophene-fused BF₂-azadipyrromethenes (aza-BDTPs) is presented. Sharp absorption and fluorescence emission bands at around 800 nm were observed for these highly photostable aza-BDTPs, with a

Full text of DOI:10.1021/ol4034622

Letter
pubs.acs.org/OrgLett
β-Thiophene-Fused BF2‑Azadipyrromethenes as Near-Infrared Dyes
Yayang Wu, Chi Cheng, Lijuan Jiao,* Changjiang Yu, Sufan Wang,* Yun Wei, Xiaolong Mu,
and Erhong Hao*
Laboratory of Functional Molecular Solids, Ministry of Education; Anhui Laboratory of Molecule-Based Materials; School of
Chemistry and Materials Science, Anhui Normal University, Wuhu, Anhui, China 241000
S
* Supporting Information
ABSTRACT: A facile synthetic route to a new class of near-
IR β-thiophene-fused BF2-azadipyrromethenes (aza-BDTPs) is
presented. Sharp absorption and fluorescence emission bands
at around 800 nm were observed for these highly photostable
aza-BDTPs, with a large absorption coefficient and very low
absorptions in the visible range from 700 to 380 nm.
aromatic groups to the 3,5-aryls of the chromophore;5,9,10 (2)
ear-infrared (NIR) dyes that absorb and/or emit light in
Nthe region ranging from 700 to 2000 nm have found the fusion of aromatic rings onto the 1,2-positions of pyrrolic
ring, as demostrated by the alfa-benzene-fused aza-BODIPY
B;11 and (3) the rigidification of 3,5-aryls via either the
installation of a six-member ring onto the 2,3-positions of
pyrrolic structure as demostrated by aza-BODIPY C12 or the
B−O chelation as demonstrated by aza-BODIPY D.13 By
“hybridizing” these approaches, herein, we report a set of β-
thiophene-fused aza-BODIPYs (aza-BDTPs), in which the
substituted thiophene rings were fused onto the 2,3-positions of
the pyrrolic structure of the chromophore. We anticipate these
aza-BDTPs as a novel NIR platform would move the
absorption bands further to approximately 800 nm.
These aza-BDTPs were synthesized from thienopyrrole 1
(Scheme 1). Regioselective and stepwise bromination of 1 with
a suitable amount of bromine gave the corresponding
dibromothienopyrrole 2a (2 equiv of Br2) and tribromothieno-
pyrrole 2b (3.5 equiv of Br2) in 96% and 87% yields,
respectively. This regioselective bromination of 1 was also
confirmed by the crystal structures of their subsequent reaction
products 3a and 3c (Figure S1, Supporting Information),
obtained from the SuzukiMiyaura cross-coupling reactions of
2 and corresponding aryl boronic acids. Upon basic hydrolysis,
compounds 3 were smoothly converted to the key synthetic
precusors 4a−d in high yields. Condensation of 4a−d with
sodium nitrite in acetic acid and the subsequent BF3
complexation using literature methods12 smoothly generated
the target aza-BDTPs 5a−d in a one-pot fashion in 54−65%
yields. These resultant aza-BDTPs were fully characterized by
NMR and HRMS.
diverse applications in medicine and material science, as
noninvasive bioimaging,1 photodynamic, photothermal ther-
apy,2 photovoltaic, optoelectronics, and laser optical recording.3
BF2-azadipyrromethenes (aza-BODIPYs)4,5 have recently re-
ceived much attention due to their remarkable photochemical
properties, especially their longer wavelength absorption and
emission properties in comparison to those of BODIPY
analogues.6−8 For example, the parent aza-BODIPY A (Figure
1) absorbs and emits at 650 and 682 nm in chloroform,
respectively.
Various elegant approches have been adopted to move the
spectra further into the NIR range include the following: (1)
the installation of electron-donating groups and/or additional
These aza-BDTPs 5 were prepared without resorting to
complicated purification processes such as chromatography
separation, except for the SuzukiMiyaura cross-coupling
Figure 1. Representative examples to move the absorption and
emission bands of aza-BODIPYs further to the NIR spectral range.
Received: November 29, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ol4034622 | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 1. Syntheses of aza-BDTPs 5a−5d
Figure 3. X-ray structures of aza-BDTP 5d. C, light gray; H, gray; N,
blue; B, dark yellow; F, green; S, yellow. tert-Butyl groups and
hydrogen atoms have been removed in both side and front views for
clarity.
products which also only need to pass through a short pad of
silica gel. For all the other steps, only workup and
recrystallization were required to afford compounds pure
enough for NMR spectroscopic analysis. It is worth noting
that, for the successful condensation of thienopyrrole 4 with
with sodium nitrite in acetic acid, the presence of the 4-aryl
group on thienopyrrole 4 (1,7-phenyls of the corresponding
aza-BDTPs, Pc rings) is essential. Our initial attempts to
condense both 4-unsubstituted thienopyrrole 4e and tribromo-
thienopyrrole 7 with sodium nitrite in acetic acid failed
(Scheme S1, Supporting Information).
was observed with the installation of additional phenyls (Pb)
(Table S1, Supporting Information). For example, the dihedral
angle between the phenyl group (Pa) and the thiophene ring is
5.3° in 3a. This increases to 31.5° in 3c with the installation of
additional phenyls (Pb), which itself has a dihedral angle of
57.6° formed with the thiophene ring. The conversion of 3c to
the target aza-BDTP 5c has little influence on these dihedral
angles. Consequently, similarly large dihedral angles between
the phenyls and the thiophene ring were observed in aza-BDTP
5c. These large dihedral angles combined with the possible
steric hindrance effect from tert-butyl groups may be
responsible for the good solubility of aza-BDTPs 5b and 5d
in most of the common organic solvents studied.
Single crystals of aza-BDTPs 5c (Figure 2), 5d (Figure 3)
and thienopyrroles 3a, 3c (Figure S1, Supporting Information)
Aza-BDTPs 5b and 5d have a very small pyrrole−pyrrole
dihedral angle (<5.6°) and thiophene−thiophene dihedral
angle (<5.2°). This indicates that the installation of thiophenes
and the associated substituted phenyls to the aza-BODIPY core
cause no structural disruption of the planar core structure. This
nearly planar aza-BDTP core results in the the π-conjugation
being well extended and is predominantly responsible for the
observed optical properties. Multiple intramolecular and
intermolecular C−H···F hydrogen bonds between F atoms
and various hydrogen atoms are formed due to the strong
electron negativity of the F atom. These strong intermolecular
hydrogen bondings also help the establishment of the crystal
packing structure (Figure S2, Supporting Information) and
make these aza-BDTPs nearly parallel to each other in a head-
to-tail orientation.
Intense and sharp absorption bands were observed for aza-
BDTPs 5 (Figure 4a). For example, in chloroform, aza-BDTP
5a has a strong absorption at 788 nm with a large absorption
coefficient (ε = 170 000 cm−1 M−1) and a full width at half-
maximum (fwhm) of 45 nm (Table 1). In comparison with that
of simple aza-BODIPY A, there is a 138 nm bathochromic shift
and a nearly 2-fold increase in the absorption coefficient. In
comparison with those reported for NIR aza-BODIPYs B, C,
and D, aza-BDTP 5a also shows a 69, 48, and 23 nm red shift of
the absorption maximum, respectively. This strong absorption
band close to 800 nm and very low absorptions in the visible
light region ranging in wavelength from 700 to 380 nm indicate
that aza-BDTP 5a may be used as a selective NIR absorber,14
Figure 2. X-ray structures of aza-BDTP 5c. C, light gray; H, gray; N,
blue; B, dark yellow; F, green; S, yellow; O, red. Methoxy groups and
hydrogen atoms have been removed in both side and front views for
clarity.
suitable for X-ray analysis were obtained from the slow
evaporation of their corresponding dichloromethane solutions.
The planar thienopyrrole planes were observed for all these
compounds. An increase of the dihedral angle defined by the
substituted phenyl rings (Pa − Pc) and the thienopyrrole planes
B
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Organic Letters
Letter
S6, Supporting Information) were observed, which may
indicate that the permanent dipole moments for 5c are similar
in the ground and excited states.15
The molecular orbital calculations for these compounds on
the density functional theory (DFT) level using a B3LYP/6-
31G basis set were performed on 5c. The LUMO distribution
of 5c was donated by all atomic orbitals in the aromatic rings
except two phenyls (Pb), while contributions to the HOMO
distribution were mainly from the aza-BODIPY core (Table S6,
Supporting Information). Intramolecular charge transfer (ICT)
from the aza-BODIPY core to the orbitals of four phenyls (Pa
and Pc) was possible in 5c, which could partly explain their low
fluorescence quantum yields, but the intramolecular C−Ar (Pa,
Pb, and Pc rings) rotations and the heavy-atom effects from
sulfur atoms may also be possible. The fluorescence decay
histograms of aza-BDTPs 5 all fitted with a single exponential
function (Figures S8−S11, Supporting Information) with the
fluorescence lifetimes τ vary between 1.18 and 1.69 ns in
chloroform (Table 1). Nevertheless, the nonradiative deactiva-
tion processes are favored for 5 with the values of knr ranging
from 0.52 × 109 s−1 to 0.81 × 109 s−1 in chloroform.
The photostabilities of aza-BDTPs 5a−d in toluene were
measured by continuous irradiation with a Xe lamp (500 W). In
comparison with a well-known commercial NIR dye ICG in
DMSO, these aza-BDTPs 5 show excellent photostability
(Figure 5) during the period of strong irradiation (26 min):
more than 98% of the amount of aza-BDTP 5b remained, while
only 83% of ICG remained under the same conditions.
Figure 4. Normalized UV−vis (a) and fluorescence (b) spectra of aza-
BDTPs 5a (black), 5b (red), 5c (blue), 5d (magenta) in chloroform.
Table 1. Photophyscial Properties of aza-BDTPs 5 at Room
Temperature in Chloroform
max
max
λabs
λem
b
a
d
e
(fwhm) / (fwhm) /
ε
τ
Kf/Knr
(109s−1
)
c
dyes
nm
nm
(cm−1 M−1
)
ϕ
(ns)
5a
5b
5c
5d
788 (45)
767 (42)
784 (57)
767 (59)
650
814 (40)
793 (48)
816 (40)
807 (53)
682
170000
223900
182000
144500
76600
0.10
0.12
0.04
0.05
1.69
1.69
1.53
1.18
0.06/0.53
0.07/0.52
0.03/0.63
0.04/0.81
f
A
0.34
a
b
Full width at half-maximum height. Excited at 730 nm.
c
Fluorescence quantum yield was obtained using Indocyanine Green
as reference compound (ϕ = 0.12 in DMSO); the standard errors are
d
Figure 5. Comparison of the photostabilities of aza-BDTPs (5 × 10−6
M) 5a (organe), 5b (yellow), 5c (blue), 5d (red) in toluene and ICG
(3 × 10−5 M, balck) in DMSO under continuous irradiation with a 500
W Xe lamp; 28 mW cm−2; 20 °C.
less than 5%. Fluorescence lifetime; standard derviations are less than
e
f
0.04 ns. Kf = ϕ/τ, Knr = (1 − ϕ)/τ. Data reported in ref 4a.
finding great applications in the NIR laser welding of
transparent polymers.
A sharp fluorescence emission maximum (fwhm = 40 nm) of
aza-BDTP 5a appears at 814 nm (Figure 4b) with an acceptable
fluorescence quantum yield (ϕ = 0.10 in chloroform),
comparable to that of commercial available ICG. The increases
of the absorption fwhm and the decreases of the fluorescence
quantum yields were observed from 5a, 5b to 5c, 5d
respectively (Table 1), correlated with the further installation
of phenyls (Pb) to the thiophene ring. Spectral shifts were
observed for aza-BDTPs 5 with the variation of solvent
polarities. For example, the absorption and emssion bands for
aza-BDTP 5c were red-shifted from 785 and 813 nm to 799
and 827 nm respectively, when the solvent was changed from
toluene to DMSO (Table S2, Supporting Information). A small
solvent dependence of the Stokes shifts (Table S4, Supporting
Information) and an unsatisfactory correlation coefficient in the
Lippert−Mataga plot of aza-BDTP 5c in 12 solvents (Figure
In conclusion, we have synthesized a set of aza-BDTPs with
strong and sharp absorption at around 800 nm, very low
absorptions in the visible light region ranging from 700 to 380
nm, and a comparable fluorescence yield to that of comercial
available ICG, without resorting to complicated purification
processes. The highly favorable photophysical properties and
efficient synthesis warrant further applications of these dyes in
biotechnology and material science.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details, NMR, additional photophysical data, and
CIF files. This material is available free of charge via the
Internet at http://pubs.acs.org.
C
dx.doi.org/10.1021/ol4034622 | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Hartmann, H.; Leo, K.; Riede, M. Chem.Eur. J. 2011, 17, 2939.
(c) Liu, H.; Mack, J.; Fuo, Q.; Lu, H.; Kobayashi, N.; Shen, Z. Chem.
Commun. 2011, 47, 12092.
AUTHOR INFORMATION
Corresponding Authors
■
(12) (a) Zhao, W.; Carreira, E. M. Angew. Chem., Int. Ed. 2005, 44,
1677. (b) Zhao, W.; Carreira, E. M. Chem.Eur. J. 2006, 12, 7254.
(13) (a) Loudet, A.; Bandichhor, R.; Burgess, K.; Palma, A.;
McDonnell, S. O.; Hall, M. J.; O’Shea, D. F. Org. Lett. 2008, 10, 4771.
(b) Kovtun, Y. P.; Yakubovskiy, V. P.; Shandura, M. P. Chem.
Heterocycl. Compd. 2008, 44, 1298.
*E-mail: jiao421@mail.ahnu.edu.cn.
*E-mail: sfwang@mail.ahnu.edu.cn.
*E-mail: haoehong@mail.ahnu.edu.cn.
Notes
The authors declare no competing financial interest.
(14) (a) Nakamura, M.; Tahara, H.; Takahashi, K.; Nagata, T.;
Uoyama, H.; Kuzuhara, D.; Mori, S.; Okujima, T.; Yamada, H.; Uno,
H. Org. Biomol. Chem. 2012, 10, 6840. (b) Wakamiya, A.; Murakami,
T.; Yamaguchi, S. Chem. Sci. 2013, 4, 1002.
(15) (a) Qin, W.; Leen, V.; Dehaen, W.; Cui, J.; Xu, C.; Tang, X.;
Liu, W.; Rohand, T.; Beljonne, D.; Van Averbeke, B. J. Phys. Chem. C
ACKNOWLEDGMENTS
■
This work is supported by the National Nature Science
Foundation of China (Grants Nos. 21072005, 21272007, and
21372011) and National Science Foundation of Anhui
Province (1208085MB29).
2009, 113, 11731. (b) Filarowski, A.; Kluba, M.; Ciesl
Koll, A.; Kochel, A.; Pandey, L.; De Borggraeve, W. M.; Van der
́
ik-Boczula, K.;
Auweraer, M.; Catalan
996.
́
, J.; Noens, N. Photochem. Photobiol. Sci. 2010, 9,
REFERENCES
■
(1) (a) Yuan, L.; Lin, W.; Zheng, K.; He, L.; Huang, W. Chem. Soc.
Rev. 2013, 42, 622. (b) Kiyose, K.; Kojima, H.; Nagano, T. Chem.
Asian J. 2008, 3, 506. (c) Yuan, L.; Lin, W.; Zhao, S.; Gao, W.; Chen,
B.; He, L.; Zhu, S. J. Am. Chem. Soc. 2012, 134, 13510. (d) Zhang, Z.;
Xu, B.; Su, J.; Shen, L.; Xie, Y.; Tian, H. Angew. Chem., Int. Ed. 2011,
50, 11654.
(2) (a) Qian, G.; Wang, Z. Y. Chem.Asian J. 2010, 5, 1006.
(b) Huang, L.; Yu, X.; Wu, W.; Zhao, J. Org. Lett. 2012, 14, 2594.
(3) (a) Law, K. Y. Chem. Rev. 1993, 93, 449. (b) Pansare, V. J.;
Hejazi, S.; Faenza, W. J.; Prud’homme, R. K. Chem. Mater. 2012, 24,
812.
(4) (a) Killoran, J.; Allen, L.; Gallagher, J. F.; Gallagher, W. M.;
O’Shea, D. F. Chem. Commun. 2002, 1862. (b) McDonnell, S. O.; Hall,
M. J.; Allen, L. T.; Byrne, A.; Gallagher, W. M.; O’Shea, D. F. J. Am.
Chem. Soc. 2005, 127, 16360. (c) McDonnell, S. O.; O’Shea, D. F. Org.
Lett. 2006, 8, 3493. (d) Wu, D.; O’Shea, D. F. Org. Lett. 2013, 15,
3392.
(5) (a) Tasior, M.; O’Shea, D. F. Bioconjugate Chem. 2010, 21, 1130.
(b) Murtagh, J.; Frimannsson, D. O.; O’Shea, D. F. Org. Lett. 2009, 11,
5386. (c) Tasior, M.; Murtagh, J.; Frimannsson, D. O.; McDonnell, S.
O.; O’Shea, D. F. Org. Biomol. Chem. 2010, 8, 522. (d) Bhuniya, S.;
Lee, M. H.; Jeon, H. M.; Han, J. H.; Lee, J. H.; Park, N.; Maiti, S.;
Kang, C.; Kim, J. S. Chem. Commun. 2013, 49, 7141. (e) Coskun, A.;
Yilmaz, M. D.; Akkaya, E. U. Org. Lett. 2007, 9, 607. (f) Adarsh, N.;
Avirah, R. R.; Ramaiah, D. Org. Lett. 2010, 12, 5720.
(6) (a) Loudet, A.; Burgess, K. Chem. Rev. 2007, 107, 4891.
(b) Ulrich, G.; Ziessel, R.; Harriman, A. Angew. Chem., Int. Ed. 2008,
47, 1184. (c) Ziessel, R.; Ulrich, G.; Harriman, A. New J. Chem. 2007,
31, 496. (d) Boens, N.; Leen, V.; Dehaen, W. Chem. Soc. Rev. 2012, 41,
1130.
(7) (a) Zhang, X.; Xiao, Y.; Qi, J.; Qu, J.; Kim, B.; Yue, X.; Belfield, K.
D. J. Org. Chem. 2013, 78, 9153. (b) Marsico, F.; Turshatov, A.;
Weber, K.; Wurm, F. R. Org. Lett. 2012, 15, 3844. (c) Jiao, C.;
Huwang, K.-W.; Wu, J. Org. Lett. 2011, 13, 632. (d) Porrel, A.; De
Nicola, A.; Ziessel, R. Org. Lett. 2012, 14, 5696. (e) Jiang, X.; Zhang, J.;
Furuyama, T.; Zhao, W. Org. Lett. 2012, 14, 248. (f) Uppal, T.; Hu, X.;
Fronczek, F. R.; Maschek, S.; Bobadova-Parvanova, P.; Vicente, M. G.
H. Chem.Eur. J. 2012, 18, 3893. (g) Yu, C.; Xu, Y.; Jiao, L.; Zhou, J.;
Wang, Z.; Hao, E. Chem.Eur. J. 2012, 18, 6437.
(8) (a) Yang, Y.; Guo, Q.; Chen, H.; Zhou, Z.; Guo, Z.; Shen, Z.
Chem. Commun. 2013, 49, 10620. (b) Awuah, S. G.; Polreis, J.; Biradar,
V.; You, Y. Org. Lett. 2011, 13, 3884. (c) Umezawa, K.; Nakamura, Y.;
Makino, H.; Citterio, D.; Suzuki, K. J. Am. Chem. Soc. 2008, 130, 1550.
(9) Bellier, Q.; Pegaz, S.; Aronica, C.; Guennic, B. L.; Andraud, C.;
Maury, O. Org. Lett. 2011, 13, 22.
(10) (a) Zhang, X.; Yu, H.; Xiao, Y. J. Org. Chem. 2012, 77, 669.
(b) Gresser, G.; Hartmann, H. M.; Wrackmeyer, K. L.; Riede, M.
Tetrahedron 2011, 67, 7148. (c) Bellier, Q.; Dalier, F.; Jeanneau, E.;
Maury, O.; Andraud, C. New J. Chem. 2012, 36, 768.
(11) (a) Lu, H.; Shimizu, S.; Mack, J.; Shen, Z.; Kobayashi, N.
Chem.Asian J. 2011, 6, 1026. (b) Gresser, G.; Hummert, M.;
D
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