Benzene-fused BODIPYs: Synthesis and the impact of fusion mode

Article abstract of DOI:10.1039/c2cc38380b

BODIPY derivatives with one or two benzene units fused at different positions are prepared using novel synthetic methods. The resulting dye 1 shows deep red fluorescence with a large Stokes shift. Dyes 2 and 3 are reported for the first time and 3 exhibits near infrared absorption. The impact of benzannulation at different positions of BODIPY is discussed, and the geometry and electronic structure are studied by DFT calculations.

Full text of DOI:10.1039/c2cc38380b

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Benzene-fused BODIPYs: synthesis and the impact
of fusion mode†
Yong Ni,a Wangdong Zeng,a Kuo-Wei Huangb and Jishan Wu*ac
Cite this: Chem. Commun., 2013,
49, 1217
Received 21st November 2012,
Accepted 18th December 2012
DOI: 10.1039/c2cc38380b
www.rsc.org/chemcomm
BODIPY derivatives with one or two benzene units fused at different
positions are prepared using novel synthetic methods. The resulting dye 1
shows deep red fluorescence with a large Stokes shift. Dyes 2 and 3 are
reported for the first time and 3 exhibits near infrared absorption. The
impact of benzannulation at different positions of BODIPY is discussed,
and the geometry and electronic structure are studied by DFT calculations.
4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene, abbreviated as BODIPY,
represents a family of extremely versatile fluorophores which are
currently attracting increasing interest among various research areas
including bio-labeling/bio-imaging1 and photovoltaic devices,2 owing
to their remarkable photophysical features, such as excellent thermal
and photochemical stability, intense absorption, sharp fluorescence
with high quantum yield, and outstanding inertness to the polarity
and pH of the environment.3 BODIPY derivatives that exhibit absorp-
tion and emission at the deep-red and near infrared (NIR) spectral
regions (>650 nm) are highly desirable in both materials science2e and
biotechnology.3a Various modification methods have been developed
to access far-red or NIR BODIPYs (Scheme 1(A)), including (i) benz-
annulation at the a bond of the BODIPY skeleton by replacement of
pyrrole with iso-indole;4 (ii) functionalization at the a position of the
pyrrole rings to generate a ‘‘push–pull’’ motif;5 (iii) replacement of the
meso-carbon by the nitrogen atom, i.e., formation of aza-BODIPYs;6
(iv) fusion of aromatic rings at the zig-zag edge of the BODIPY
by oxidative cyclodehydrogenation reaction as reported by us;7 and
(v) annulation at the b bond of the BODIPY skeleton by replacement
of the pyrrole rings with benzofuro[3,2-b]pyrrole, thianaphtheno-
[3,2-b]pyrrole, and biphenyl-fused pyrrole units.8 Indole can also be
regarded as a benzannulated pyrrole. However, to the best of our
Scheme 1 (A) Various approaches towards BODIPYs with longer absorption
and emission wavelengths. (B) Benzene-fused BODIPYs synthesized in this study.
(C) Reagents and conditions: (a) DMF, 90 1C, 16 h, 72%; (b) 2,4-dimethylpyrrole, POCl3,
DCM, r.t., 12 h; (c) BF3ÁOEt2, TEA, DCM, 2 h, 42% for 1 from 5, 20% for 2 from 9, 24%
for 3 from 13; (d) phenylboronic acid, Pd(PPh3)4, Na2CO3, toluene, 110 1C, 24 h, 81%;
(e) 10% NaOH, DMSO, EtOH, 50 1C, 94%; (f) benzaldehyde, 37% HCl, MeOH/EtOH, r.t.,
12 h; (g) DDQ, DCM, refluxing, 2 h; (h) i: LDA, THF, À78 1C, 2 h; ii: 2-iodobenzoylchloride,
r.t., 12 h, 21%; (i) Cu, DMF, 140 1C, 3 h, 95%.
knowledge, replacement of pyrrole rings in the BODIPY with indole
units to generate indole-based BODIPYs has rarely been reported so
far.9 Moreover, the oxidative fusion strategy to introduce an aryl unit
onto the zig-zag edge of BODIPY encountered a severe limitation,
namely that the aryl unit must be suitably electron-rich.7 Therefore,
the phenyl ring without an electron-donating group cannot be
successfully fused onto the zig-zag edge using this strategy.
a Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543,
Singapore. E-mail: chmwuj@nus.edu.sg; Fax: +65-67791691; Tel: +65-65162677
b King Abdullah University of Science and Technology (KAUST), Division of Physical
Sciences and Engineering and KAUST Catalysis Center, Thuwal 23955-6900,
Saudi Arabia
c Institute of Materials Research and Engineering, A*Star, 3 Research Link, 117602,
Singapore
† Electronic supplementary information (ESI) available: Synthetic procedures and
characterization data, summary of electrochemical data, and DFT calculation
details. See DOI: 10.1039/c2cc38380b
Herein, we report convenient synthetic routes to replace the pyrrole
with indole to achieve indole-based BODIPY 1 and bisindole-based
c
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BODIPY 2, which can also be regarded as benzo[b]-fused BODIPYs
(Scheme 1(B)). Meanwhile, a novel strategy to prepare BODIPY 3 with
one benzene unit fused at the b bond and one benzene ring fused at
the zigzag edge will also be demonstrated. Their geometries, electronic
structures and photophysical properties are investigated to afford a
fundamental understanding of these new benzene-fused BODIPY
dyes. A tetramethyl-BODIPY dye 4 was also prepared for comparison.10
The asymmetric benzo[b]-fused BODIPY 1 was synthesized
through a two-step synthetic route (Scheme 1(C)). The alkylation–
condensation between 2-amino-benzophenone and 2-bromoacetyl-
phenone gave 2-benzoyl-3-phenylindole 5 in 72% yield.11 Compound
5 was then reacted with 2,4-dimethylpyrrole in the presence of POCl3,
followed by addition of triethylamine (TEA) and complexation with
BF3ÁOEt2 to afford the benzo[b]-fused BODIPY 1 as a deep red solid
in a total yield of 42%. This method likely can be used to prepare a
series of benzo[b]-fused BODIPY derivatives since the alkylation–
condensation sequence between o-amino ketones and a-bromo
ketones provides ready access to a wide variety of 2-acylindoles.11
The symmetric BODIPY 2 was prepared through the condensation of
indole derivatives with the corresponding aldehyde. The Suzuki
coupling reaction of N-tosyl-3-iodoindole 7 with phenylboronic
acid gave the N-tosyl-3-phenylindole 8 in 88% yield. After hydro-
lysis, the resulting 3-phenylindole 9 was reacted with benzalde-
hyde in the presence of concentrated hydrochloric acid to
produce the key intermediate 10.12 Without further purification,
this intermediate was dissolved in anhydrous dichloromethane
(DCM) followed by oxidation with DDQ and complexation with
borontrifluoride to afford the dibenzo[b]-fused BODIPY 2 as a
blue dye in an overall 20% yield. To synthesize compound 3, we
attempted the condensation of a fused indole–ketone inter-
mediate 13 with pyrrole for the first time. Compound 7 was treated
with strong base LDA for lithiation at the 2-position, then reacted
with 2-iodobenzoyl-chloride to generate 11. This compound was
then treated with activated copper for intra-molecular Ullmann
coupling reaction to give 12,13 which after hydrolysis afforded the
key intermediate benzene-fused keto-indole 13. Using a similar
synthetic methodology to BODIPY 1, BODIPY 3 was successfully
prepared as a pink-red solid in an overall yield of 24% from 13. The
structures of all these compounds were unambiguously identified
by NMR spectroscopy and mass spectrometry (ESI†).
Fig. 1 UV-vis-NIR absorption spectra of 1–4 and normalized emission spectra of
1 in DCM. Inset is the photograph of the solutions of 1–4.
The electrochemical properties of 1, 2 and 3, together with 4 for
comparison, were investigated by cyclic voltammetry in DCM
solution containing 0.1 M tetra-n-butylammonium hexafluoro-
phosphate as the supporting electrolyte. As shown in Fig. 2,
compounds 4, 1 and 2 all exhibit one quasi-reversible oxidation
wave and one reversible reduction wave with half-wave potentials at
1.05 V, À1.68 V for 4, 1.11 V, À1.24 V for 1, and 1.20 V, À0.70 V
(vs. Fc+/Fc) for 2, respectively. The half-wave potentials of the
oxidation waves of these three compounds show only a slight
difference, while the reduction potentials exhibit a positive shift
from 4 to 1 then to 2, indicating that fusion of a benzene ring at the
b bond of BODIPY can efficiently decrease the LUMO energy level,
but shows a less impact on the HOMO energy level. HOMO energy
levels of À5.68 eV, À5.79 eV, À5.88 eV and LUMO energy levels of
À3.32 eV, À3.69 eV, À4.19 eV were estimated for 4, 1 and 2,
respectively, based on the onset potential of the first oxidation and
reduction waves. Compound 3 displays one reversible oxidation
wave with a half-wave potential of 0.78 V and two reversible
reduction waves with half-wave potentials of À0.85 V and À1.61 V.
The HOMO energy level was estimated to be À5.44 eV, 0.33 eV
higher than that of 1, while the LUMO energy level is À4.08 eV,
0.39 eV lower than that of 1. Thus, the fusion of a benzene unit at the
zigzag edge of BODIPY can effectively extend the p-delocalization,
resulting in an efficiently narrowed energy gap.7 Electrochemical
energy gaps of 2.36 eV for 4, 2.10 eV for 1, 1.69 eV for 2 and 1.36 eV
The UV-vis-NIR absorption spectra of compounds 1–4 and the
normalized emission spectrum of 1 are shown in Fig. 1. BODIPY 1
shows a relatively broad absorption band with maximum at 512 nm
(log e = 4.62, e: molar extinction coefficient in MÀ1 cmÀ1), with a
slight red-shift by 12 nm relative to 4 (lmax = 500 nm, log e = 4.90). It
exhibits an emission band centered at 655 nm with a fluorescence
quantum yield of ca. 10% in DCM. Interestingly, a very large Stokes
shift of 143 nm was observed, which makes this dye attractive for bio-
imaging application after modification at the 3-methyl site.14 BODIPY
2 displays an even broader absorption band (covering from 500 nm to
700 nm) with a more red-shifted lmax of 568 nm. However, no
fluorescence was observed. BODIPY 3 exhibits three absorption
bands, an intense band at 391 nm with a relatively large coefficient
(log e = 5.0), a band at 518 nm, which is similar to that of BODIPY 1,
and a broad band ranging from 600 nm to 1100 nm, indicating a
highly extended p-delocalization caused by fusion of a benzene ring
at the zigzag edge of the BODIPY core.
Fig. 2 Cyclic voltammograms of 1–4 in DCM with 0.1 M Bu4NPF6 as a support-
ing electrolyte, AgCl/Ag as a reference electrode, Au disk as a working electrode,
Pt wire as a counter electrode, and a scan rate of 50 mV sÀ1. Fc+/Fc was used as
external reference.
c
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avoid intra-molecular charge transfer caused by the electro-donating
groups. Dye 1 exhibits long wavelength fluorescence with a large
Stokes shift, which makes it attractive for bio-imaging application,
and this research is underway in our laboratories.
J.W. acknowledges financial support from the SPORE (COY-15-
EWI-RCFSA/N197-1), BMRC-NMRC grant (no. 10/1/21/19/642),
and IMRE Core funding (IMRE/10-1P0509). K.-W.H. acknowledges
financial support from KAUST.
Notes and references
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successfully prepared for the first time using new synthetic methods.
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c
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