Tetrastyryl-bodipy dyes: Convenient synthesis and characterization of elusive near IR fluorophores

Article abstract of DOI:10.1021/ol9019056

1,3,5,7-Tetramethyl-Bodipy derivatives undergo Knoevenagel-type condensations with aromatic aldehydes to ultimately yield tetrastyryl-Bodipy derivatives. The resulting dyes absorb and emit strongly In the near IR. As the versatility of the Bodipy dyes are

Full text of DOI:10.1021/ol9019056

ORGANIC
LETTERS
2009
Vol. 11, No. 20
4644-4647
Tetrastyryl-Bodipy Dyes: Convenient
Synthesis and Characterization of
Elusive Near IR Fluorophores
Onur Buyukcakir,† O. Altan Bozdemir,† Safacan Kolemen,‡ Sundus Erbas,† and
Engin U. Akkaya*,†,‡
Department of Chemistry and UNAM-Institute of Materials Science and
Nanotechnology, Bilkent UniVersity, 06800 Ankara, Turkey
eua@fen.bilkent.edu.tr
Received August 18, 2009
ABSTRACT
1,3,5,7-Tetramethyl-Bodipy derivatives undergo Knoevenagel-type condensations with aromatic aldehydes to ultimately yield tetrastyryl-Bodipy
derivatives. The resulting dyes absorb and emit strongly in the near IR. As the versatility of the Bodipy dyes are fully appreciated, these new
tetrastyryl dyes are likely to be featured in a variety of functional supramolecular systems.
For more than three decades after their initial synthesis,1
Bodipy dyes were known only as bright fluorescent dyes for
use in cellular imaging as supplied by a few commercial
sources. However, especially within the last five years, there
has been a veritable Bodipy renaissance.2 This is in large
part sparked by the new tactics3 in the functionalization of
the Bodipy core, which led to the synthesis of longer
wavelength absorbing/emitting fluorescent dyes,4 energy
transfer cassettes,5 light harvesters,6 sensitizers for solar cells7
and photodynamic therapy,8 nonlinear optical materials,9
mesogenic materials,10 supramolecular polymers,11 fluores-
cent chemosensors,12 and molecular logic systems.13 This
remarkable versatility of Bodipy dyes, reminiscent of struc-
turally related porphyrins, prompted Ziessel to label Bodipy
as “porphyrin’s little sister”.2c
The parent Bodipy unit has a major absorption peak
(S0-S1 transition) near 500 nm; however, incorporation of
fused aromatic rings and/or aryl substituents,4d-i ethynylaryl
substitution,14 and aza-substitution at the meso (8)
position4b,c,k,15 push this peak into the red end of the visible
† UNAM-Institute of Materials Science and Nanotechnology.
(3) (a) Rurack, K.; Kollmannsberger, M.; Daub, J. Angew. Chem., Int.
Ed. 2001, 40, 385–387. (b) Ulrich, G.; Goze, C.; Guardigli, M.; Roda, A.;
Ziessel, R. Angew. Chem., Int. Ed. 2005, 44, 3694–3698. (c) Dost, Z.;
Atilgan, S.; Akkaya, E. U. Tetrahedron 2006, 62, 8484–8488. (d) Rohand,
T.; Baruah, M.; Qin, W.; Boens, N.; Dehaen, W. Chem. Commun. 2006,
266–268. (e) Li, L. L.; Han, J. Y.; Nguyen, B.; Burgess, K. J. Org. Chem.
2008, 73, 1963–1970. (f) Han, J. Y.; Gonzales, O.; Aguilar-Aguilar, A.;
Pena-Cabrera, E.; Burgess, K. Org. Biomol. Chem. 2009, 7, 34–36.
‡ Department of Chemistry.
(1) Treibs, A.; Kreuzer, F. H. Justus Liebigs Ann. Chem. 1968, 718,
208.
(2) (a) Ziessel, R.; Ulrich, G.; Harriman, A. New J. Chem. 2007, 31,
496–501. (b) Loudet, A.; Burgess, K. Chem. ReV. 2007, 107, 4891–4932.
(c) Ulrich, G.; Ziessel, R.; Harriman, A. Angew. Chem., Int. Ed. 2008, 47,
1184–1201.
10.1021/ol9019056 CCC: $40.75
Published on Web 09/16/2009
 2009 American Chemical Society

spectrum. All of these approaches may be useful in certain
applications, nevertheless mono- and distyryl modifications
seem to offer a greater degree of versatility as judged by
the recent interest,7b,c,16 apart from our group. This clearly
stems from the following facts: (i) Knoevenagel reaction of
the 3- and 5-methyls is in most cases high yielding; (ii) the
reaction conditions tolerate the use of a variety of aldehydes
with different stereoelectronic characteristics; (iii) strong
charge donor substituents are likely to yield switchable
fluorescent molecules with internal charge transfer charac-
teristics useful as chemosensors and molecular logic
gates.12,13
The results suggested that the methyl groups in positions
1 and 7 could be almost as acidic as 3,5-methyls. H NMR
1
Figure 2
1-5.
. Structures of the quadruple Knoevenagel reaction products
spectra should provide additional support for this argument;
however, the correlation between acidity and the chemical
shifts is problematic due to magnetic anisotropy effects. In
the 8-phenyl-substituted Bodipy dyes, 1,7-methyls are in the
shielding zone of the phenyl substituents and experience a
shielding by approximately 0.7 ppm. The situation is more
revealing in the tetramethyl and pentamethyl derivatives
lacking the phenyl substituent (Figure 1). The chemical shifts
for two sets of methyl protons (3,5 and 1,7) resonate closely
especially in the pentamethyl derivative, which could be
interpreted as a sign of comparable acidity. Encouraged by
these observations, we looked for likely conditions to extend
Knoevenagel condensation to other methyl substituents on
the Bodipy core. Our earlier experience with the distyryls
led us to start with Bodipy dyes with electron-withdrawing
substituents, as they clearly enhance the acidity of the methyl
substituents.
Figure 1. 1,3,5,7-Tetramethyl- and 1,3,5,7,8-pentamethyl-Bodipy
1
derivatives; numbering and relevant H NMR chemical shifts in
CDCl3.
While considering the possibility of further functionaliza-
tion of the Bodipy core, we carried out a Mulliken-charge
analysis on the core carbon atoms of tetramethyl-Bodipy.
The electron density of the carbon atoms varies in the
following order: 2,6 . 1,7 > 3,5.
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4645

and the aromatic aldehyde was p-anisaldehyde (Figure 2).
The reaction conditions were similar to mono- and distyryl
functionalizations (Supporting Information). A similar reac-
tion with a Bodipy derivative which has 4-t-butylphenyl-
ethynyl substituents on the 2,6-positions produced expected
tetrastyryl product 3, requiring a slightly longer time under
reflux for full conversion. It is also interesting to note that
Knoevenagel condensations of this kind have been carried
out with tetramethyl-substituted Bodipy’s for almost a
decade, but until now, no one has identified triple or
quadruple condensation products.
Figure 4. One-pot synthesis of four different styryl-Bodipy dyes.
The reactions can be stopped at appropriate times to maximize the
yield for a particular derivative. The inset picture shows the colors
under ambient light (top half) and when excited using a hand-held
UV lamp at 360 nm (bottom half).
1
Figure 3
.
Structures and partial H NMR spectra of the distyryl
(top) and the tetrastyryl-Bodipy 5 (bottom). A significant upfield
shift of one pair (color coded in red) of trans-vicinally coupled
protons due to their protrusion toward the meso-phenyl ring is
obvious. It is a signature feature for 8-phenyl-substituted tetrastyryl-
Bodipy’s. The other pair (green) is not affected.
Figure 5. Absorption and emission spectra of the compounds 6-10.
first methyls to react are exclusively 3,5-methyls, and tri-
and tetra-substituted products are obtained only when the
concentration of all the reactants is increased by the removal
of most of the solvent. Thus, by simple condensation
reactions, the absorption peak of a Bodipy dye 6 can be
pushed stepwise from 498 to 572, 645, 665, and 689 nm.
Next, we wanted to demonstrate that the reaction is not
limited to p-anisaldehyde. Condensation with p-N,N-dim-
ethylaminobenzaldehyde also proceeds smoothly. The spec-
troscopic data for the new tetrastyryl-Bodipy dyes are
presented in Table 1. The tetrastyryl dyes 4 and 5 are true
near IR dyes, absorbing maximally around 800 nm and
emitting maximally around 835 nm in chloroform. The peaks
are also relatively sharp as judged by the less than 50 nm
fwhm (full-width at half-maximum) values. The dyes have
very large extinction coefficients rivaling those of typical
cyanine dyes. Their quantum yields were also found to be
moderate to high, except for dimethylaminostyryl dye 5. The
strong charge transfer and highly polar excited states in 4
and 5 tend to decrease the emission quantum yield, so this
is not unexpected.
Knoevenagel reaction introduces styryl groups exclusively
in a trans (E) configuration. In distyryl compounds, this is
easily evidenced by the existence of two pairs of trans-
coupled protons with a chemical shift difference of ap-
proximately 1 ppm. In the tetrastyryl compounds, there are
two additional pairs of protons showing peaks around 7.7
and 6.1 ppm. Figure 3 shows the aromatic regions of the 1H
NMR spectra of the tetrastyryl-bodipy 5 and the intermediate
distyryl-bodipy for comparison. The integration ratios and
the upfield shift of one pair of ethylenic protons are in
accordance with the structure of the tetrastyryl dyes.
To gain insight into the scope of the reaction, we tried
the reaction with bromo-substituents and with no substituents
on the 2,6-positions. The 2,6-dibromo derivative reacted as
efficiently as the ethynyl-substituted derivatives to yield the
tetrastyryl compound. 2,6-H Bodipy derivative 6, as ex-
pected, reacted slowly, but this allowed us a remarkable feat.
By simply stopping the reaction at different times, we could
easily isolate mono-, di-, tri-, and tetrastyryl derivatives as
the major products (Figure 4). This fact alone should give a
hint to the versatility of this reaction. The absorption and
the emission spectra of this series of Bodipy dyes (7-10)
are shown in Figure 5. It is also interesting to note that the
Bodipy dyes proved to be more than simple fluorophores.
We are confident that such straightforward functionalization
and derivatization methodologies are likely to add to their
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Org. Lett., Vol. 11, No. 20, 2009

these novel and easily accessible chromophores are expected
to make an impact as sensitizers for photodynamic therapy
and dye sensitized solar cells, as structural units in dendritic
light harvesters, and as versatile building blocks in highly
structured supramolecular entities. Setting aside the reversible
oxygen carrying function, it appears that the new generation
of Bodipy dyes is poised to compete with porphyrins as one
of the prime building blocks in supramolecular chemistry.
Our work along these lines is in progress.
Table 1. Spectral Data for Tetrastyryl-Bodipy Dyes and
Selected Intermediate Dyes Isolated from the Knoevenagel
Reaction Media
compounda
λabs (nm)
λem (nm)
Φfb
εmax
c
1
2
3
4
5
7
8
9
10
700
721
732
802
797
572
645
665
689
727
747
756
837
835
585
660
682
710
0.12
0.42
0.23
0.13
0.05
0.92
0.37
0.35
0.34
48 800
88 200
173 900
141 500
144 700
58 900
116 400
96 900
127 900
Acknowledgment. Financial support by the Turkish
¨
Academy of Sciences (TUBA) is gratefully acknowledged.
S.E. thanks TUBITAK for a scholarship.
a Data acquired in CHCl3 in dilute solutions. b Relative quantum yields.
Supporting Information Available: Experimental pro-
cedures, structural proofs, and spectral data for all new
compounds are provided. This material is available free of
charge via the Internet at http://pubs.acs.org.
c Unit: cm-1 M-1
.
impressive versatility. It appears that by fine-tuning the
reaction conditions it should be possible to tether four
different styryl groups to the Bodipy core. Needless to say,
OL9019056
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