Regioselective synthesis of 5-monostyryl and 2-tetracyanobutadiene BODIPY dyes

Article abstract of DOI:10.1021/ol201600s

Several unsymmetrically 2,5-disubstituted BODIPY dyes were obtained from 2-substituted derivatives (iodo, ethynylaryl) using a regioselective Knoevenagel condensation reaction with dimethylaminobenzaldehyde. The unsaturated, unsymmetrical 2-ethynyl-5-styr

Full text of DOI:10.1021/ol201600s

ORGANIC
LETTERS
2011
Vol. 13, No. 19
4996–4999
Regioselective Synthesis of 5-Monostyryl
and 2-Tetracyanobutadiene BODIPY Dyes
Songlin Niu,† Gilles Ulrich,*,† Pascal Retailleau,‡ and Raymond Ziessel*,†
ꢀ
LCOSA, UMR7515, CNRS/Universite de Strasbourg/ECPM, 25 rue Becquerel, 67087
Strasbourg, Cedex 02, France, and Laboratoire de Crystallochimie, ICSN-CNRS, Bat
27-1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, Cedex, France
gulrich@unistra.fr; ziessel@unistra.fr
Received June 14, 2011; Revised Manuscript Received August 29, 2011
ABSTRACT
Several unsymmetrically 2,5-disubstituted BODIPY dyes were obtained from 2-substituted derivatives (iodo, ethynylaryl) using a regioselective
Knoevenagel condensation reaction with dimethylaminobenzaldehyde. The unsaturated, unsymmetrical 2-ethynyl-5-styryl-BODIPY undergoes a
regioselective [2 þ 2] cycloaddition reaction with tetracyanoethylene leading to the 1,1,4,4-tetracyanobuta-1,3-diene (TCBD) derivative. This
shows rich redox activity with two reversible oxidation and three reversible reduction waves at þ0.72 V, þ1.04 V; ꢀ0.32 V, ꢀ0.78 V, and ꢀ1.50 V,
respectively.
In the past ten years, the π-extended styryl derivatives
of 4,40-difluoro-4-bora-3a,4a-diaza-s-indacene, BODIPY,
dyes have been widely studied due to their remarkable
optical/electrochemical properties.1 They have found wide-
spread applications in biological labeling2 andcell imaging,3
as logic gates4 and ion sensors,5 and in dye-sensitized solar
cells6 and solution-processed bulk heterojunction solar cells.7
In general, the formation of mono or distyryl BODIPY
dyes using a Knoevenagel condensation reaction has started
withasymmetric BODIPY dye. Inmanycases, anexcessof
aldehyde has been used to convert the starting BODIPY
dye fully to its distyryl derivative. Sophisticated dyes
bearing preorganized functions have been prepared
thereby.8 However, a supplementary fine-tuning of the
absorption and emission wavelengths is crucial for molec-
ular design and engineering of fluorophores for specific
applications. Thus, panchromatic dyes have been synthe-
sized recently by the use of successive Knoevenagel reac-
tions in a controlled fashion to provide oligomeric BODIPY
dyes.9 Herein, we disclose the regioselective preparation of
†
ꢀ
LCOSA, UMR7515, CNRS/Universite de Strasbourg/ECPM.
‡ Laboratoire de Crystallochimie, ICSN-CNRS.
(1) (a) Rurack, K.; Kollmannsberger, M.; Daub, J. New J. Chem.
2001, 25, 289. (b) Saki, N.; Dinc, T.; Akkaya, E. U. Tetrahedron 2006, 62,
2721. (c) Ziessel, R.; Retailleau, P.; Elliott, K. J.; Harriman, A. Chem.;
Eur. J. 2009, 15, 10369. (d) Ziessel, R.; Ulrich, G.; Harriman, A.;
Alamiry, M. A. H.; Stewart, B.; Retailleau, P. Chem.;Eur. J. 2009,
15, 1359.
(2) Niu, S. L.; Massif, C.; Ulrich, G.; Ziessel, R.; Renard, P.-Y.;
Romieu, A. Org. Biomol. Chem. 2010, 9, 66.
(3) (a) He, H.; Lo, P.-C.; Yeung, S.-L.; Fong, W.-P.; Ng, D. K. P.
Chem. Commun. 2011, 47, 4748. (b) Didier, P.; Ulrich, G.; Mely, Y.;
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Soc. 2010, 132, 8029.
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4792.
(7) (a) Rousseau, T.; Cravino, A.; Roncali, J.; Bura, T.; Ulrich, G.;
Ziessel, R. Chem. Commun. 2009, 1673. (b) Rousseau, T.; Cravino, A.;
Roncali, J.; Bura, T.; Ulrich, G.; Ziessel, R. J. Mater. Chem. 2009, 16,
2298. (c) Rousseau, T.; Cravino, A.; Ripaud, E.; Leriche, P.; Rihn, S.; De
Nicola, A.; Ziessel, R.; Roncali, J. Chem. Commun. 2010, 46, 5082. (d)
Kim, B.; Ma, B.; Donuru, V. R.; Liu, H.; Frechet, J. M. J. Chem.
Commun. 2010, 46, 4148.
(8) Ziessel, R.; Bura, T.; Olivier, J.-H. Synlett 2010, 2304.
(6) (a) Erten-Ela, S.; Yilmaz, M. D.; Icli, B.; Dede, Y.; Icli, S.;
Akkaya, E. U. Org. Lett. 2008, 10, 3299. (b) Kolemen, S.; Cakmak,
Y.; Erten-Ela, S.; Altay, Y.; Brendel, J.; Thelakkat, M.; Akkaya, E. U.
Org. Lett. 2010, 12, 3812.
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2010, 122, 6809. (b) Zhu, S.; Zhang, J.; Vegesna, G. K.; Pandey, R.; Luo,
F.-T.; Green, S. A.; Liu, H. Chem. Commun. 2011, 47, 3508.
r
10.1021/ol201600s
Published on Web 09/08/2011
2011 American Chemical Society

5-substituted dyes starting from BODIPY derivatives
displaying a bulky group in the 2-position by using a
Knoevenagel reaction with dimethylaminobenzaldehyde.
Initially, the BODIPY derivatives 2 and 3 were prepared
by a Sonogashira cross-coupling reaction of the 2-iodo
derivative 1 with the corresponding ethynyl derivatives
shown in Scheme 1.10 Compounds 1, 2, and 3 are a rep-
resentative panel of dyes with substituents of varying elec-
tronic influence: the iodine atom is considered as both an
electron donor (by conjugation) and an electron acceptor
(by induction); the p-methoxybenzene-ethynyl as a donor
group; and the p-nitrobenzene-ethynyl as an electron-
withdrawing group.
residue. The molecular conformation of the monostyryl 4 is
closely similar to that of monostyryl BODIPYs described in
the literature.12 The BODIPY core remains planar, with
the double bond slightly twisted away from the BODIPY
plane with a torsion angle (C6ꢀC5ꢀC10ꢀC20) of 8.67° and
the phenyl ring slightly twisted (by 8.06°) relative to the
double bond (C10ꢀC20ꢀC1CꢀC6C). The distance between
0
0
˚
atoms C1 and C2 is 1.342 A, that between C3 and I1 is
˚
˚
2.060 A, and that between C4C and N3 is 1.386 A,
respectively. These values are in keeping with CdC, C;I,
and C;N bonds, respectively.1b,c,11
Scheme 1. Synthesis of the Precursor Ethynyl-BODIPY
The Knoevenagel condensation reaction of compounds
1ꢀ3 with dimethylaminobenzaldehyde was carried out
under standard conditions,11 and the condensation was
found to occur principally at the 5-position of the BOD-
IPY core, leading to the 5-monostyryl BODIPY deriva-
tives 4ꢀ6 in 27 to 52% yield (Scheme 2). Compound 6 was
obtained in a relatively low yield, due to the decrease
of nucleophilicity of the 5-methyl group induced by the
conjugated nitro function.
Figure 1. ORTEP view of compound 4. Displacement ellipsoids
are drawn at the 30% probability level.
Reaction of 5 with tetracyanoethene was conducted in
the manner recently described by Diederich et al. for the
reaction of TCNE with electron-rich alkyne derivatives.13
Such groups undergo selectively a [2 þ 2] cycloaddition
reaction with TCNE, followed by the formation of an
intermediate cyclobutene, which subsequently undergoes
ring opening, leading to the 1,1,4,4-tetracyanobuta-1,
3-diene (TCBD) derivative 7 shown in Scheme 3. The
reactivity of various donor-substituted alkynes with
TCNE has comprehensively been reported.14
Scheme 2. Synthesis of Monostyryl BODIPY
Scheme 3. Synthesis of TCBD-BODIPY 7
All these compounds were isolated by column chroma-
tography. The chemical structures of the monostyryl
BODIPY dyes were confirmed by 1H NMR and 2D COSY
NMR, in particular by the shift in the peak due to the β-
pyrrolic proton at the 6-position of the BODIPY from 6.0
to 6.6 ppm, due to the formation of the styryl group at the
5-substitution position. This was consistent with published
work on various mono and distyryl BODIPY dyes.8,9c
A single-crystal, X-ray study confirmed the expected
structure (Figure 1) and the regioselective formation of
the monostyryl function on the side opposite to the iodo
€
(12) Yu, Y. H.; Descalzo, A.; Shen, Z.; Rohr, H.; Liu, Q.; Wang,
Y. W.; Spieles, M.; Li, Y. Z.; Rurack, K.; You, X. Z. Chem.;Asian J.
2006, 1, 176.
(13) (a) Kato, S. I.; Kivala, M.; Schweizer, W.; Boudon, C.;
Gisselbrecht, J. P.; Diederich, F. Chem.;Eur. J. 2009, 15, 8687. (b)
Kato, S.-I.; Diederich, F. Chem. Commun. 2010, 46, 1994.
(14) Michinobu, T.; Boudon, C.; Gisselbrecht, J.-P.; Seiler, P.;
Frank, B.; Moonen, N. N. P.; Gross, M.; Diederich, F. Chem.;Eur.
J. 2006, 12, 1889.
(10) Bonardi, L.; Ulrich, G.; Ziessel, R. Org. Lett. 2008, 10, 2183.
(11) Bura, T.; Hablot, D.; Ziessel, R. Tetrahedron Lett. 2011, 52,
2370.
Org. Lett., Vol. 13, No. 19, 2011
4997

Table 1. Optical Data for the BODIPY Derivativesa
compound (solvent)
λabs (nm)
ε (Mꢀ1 cmꢀ1
)
λ
em (nm)
Φ (%)
τ (ns)
kr (107 sꢀ1
)
knr (107 sꢀ1
)
ΔS (cmꢀ1 b
)
4 (Dioxane)
606
566
602
563
600
561
620
582
617
580
613
576
80 300
106 000
94 000
114 700
92 300
94 700
92 400
70 100
88 200
76 200
71 600
73 700
658
587
699
574
705
573
660
628
691
625
721
612
66
20
14
13
9
3.3
2.5
2.1
1.3
2.5
1.2
2.6
2.1
2.1
2.1
1.1
ꢀ
20.0
8.0
10.3
32.0
41.0
66.9
36.4
69.2
13.1
41.9
37.6
46.2
82.7
ꢀ
13 04
632
4 (Dioxane þ Hþ)
4 (EtOH)
6.7
23 05
340
4 (EtOH þ Hþ)
4 (CH3CN)
10.0
3.6
24 82
373
4 (CH3CN þ Hþ)
17
66
12
21
3
14.2
25.4
5.7
5 (Dioxane)
978
5 (Dioxane þ Hþ)
5 (EtOH)
12 59
17 36
12 41
24 44
10 21
10.0
1.4
5 (EtOH þ Hþ)
5 (CH3CN)
9
8.2
5 (CH3CN þ Hþ)
2
ꢀ
a Quantum yield determined in dilute solution (1 ꢁ 10ꢀ6 M) using rhodamine 6G (Φ = 0.78 in water, λexc = 488 nm), or cresyl violet as reference
(Φ = 0.51 in EtOH, λexc = 578 nm).22 All φ are corrected for changes in refractive index. kr and knr were calculated using the following equations:
kr = ΦF/τ, knr = (1 ꢀ ΦF)/τ. b ΔS = Stokes shift.
The reaction also appears to be regioselective, and no
addition to the styryl double bond is seen. The inertness of
double bonds toward TCNE has already been reported.15
The purple, amorphous product 7 was easily purified by
flash chromatography, withan excellentyield. This selective
cycloaddition reaction generates a pushꢀpullꢀpull chro-
mophore, which displays a pronounced internal charge
transfer transition (ICT). In addition, the TCBD residue
imports good solubility to the dye 7 in common solvents
due to the nonplanarity of the molecule, which efficiently
prevents the formation of aggregates.16
s
ꢀ1) and a decrease of the radiative decay constant kr ((25.4
to 8.2) ꢁ 107 sꢀ1). The same trends are observed for dye 4
and can be attributed to the acceleration of internal
conversion as the energy gap between ground state and
excited state decreases. The protonation of 4 and 5 by
passing HCl vapor into their solutions was used to
“switch off” the ICT transition between the dimethyl-
anilino group and the BODIPY moiety. In absorption,
the protonation results in a hypsochromic shift of about
40 nm for 4 and 5, which is independent of the solvent
polarity. In emission, the protonation also results in a large
hypsochromic shift. The emission maximum is centered
The optical properties of the monostyryl BODIPY dyes 4,
5 and TCBD dye 7 in various solvents are summarized
in Table 1. In solution, the UVꢀvis absorption spectra of
both styryl compounds are similar to those of monostyryl
BODIPYs previously described.17 A strong absorption
band between 500 and 700 nm is observed with an absorp-
tion coefficient in the 70 000ꢀ110 000 Mꢀ1 cmꢀ1 range,
corresponding to the S0fS1 transition of the BODIPY core.
For 4 and 5, the absorption maximum is centered at 603 ( 3
and 617 ( 3 nm, respectively. A weak solvent dependence is
observed for both molecules in absorption (Figure 2).
In contrast, the fluorescence emission spectra of both
compounds are strongly dependent on the dipole moment
of the solvent. For 4, the emission maximum shifts from
658 nm in dioxane to 705 nm in acetonitrile. For 5, the
emission maximum shifts from 660 nm in dioxane to 721
nm in acetonitrile. The bathochromic shifts with a con-
comitant decrease of fluorescence quantum yield (φ) and
lifetime (τ) are observed for both molecules in solvents of
stronger dipole moment. For 5, the quantum yield (φ) and
lifetime (τ) decrease from dioxane (φ = 0.66, τ = 2.6 ns) to
CH3CN (φ = 0.09, τ = 1.1 ns), accompanying an increase
in the nonradiative decay constant knr ((1.3 to 8.3) ꢁ 108
(15) Wu, X.; Wu, J.; Liu, Y.; Jen, A. K.-Y. J. Am. Chem. Soc. 1999,
121, 472.
(16) Esembeson, B.; Scimeca, M. L.; Michinobu, T.; Diederich, F.;
Biaggio, I. Adv. Mater. 2008, 20, 4584.
(17) Rurack, K.; Kollmannsberger, M.; Daub, J. Angew. Chem., Int.
Figure 2. Top: absorption spectra of 5. Bottom: absorption
spectra of 7.
Ed. 2001, 40, 385.
4998
Org. Lett., Vol. 13, No. 19, 2011

at 573 ( 7 nm for 4 and 620 ( 8 nm for 5. For both
molecules, a small hypsochromic shift is observed in more
polar solvents. However, instead of resulting in a higher
fluorescence quantum yield,1c protonation here produces
rather low quantum yields (φ) for 4 (φ decreases from 0.20
to 0.13) and 5 (φ decreases from 0.12 to 0.02), due to a
faster nonradiative decay knr. A decrease of the lifetime in
more polar solvents is also observed for both molecules.
The solvent dependency of the spectra of protonated 4 and
5 can be attributed to the ICT character of the major
absorption. We presume that after protonation the amino
group becomes the acceptor group, while the iodine atom
of4andtheethynylanisolemoietyof5act as donor groups.
The electronic signature moves from a push/π/push situa-
tion to a pull/π/push case.1b Nonetheless, the CT character
in both cases is rather modest, probably due to the weak
electronic acceptor nature of the ammonium center. In
the absorption spectra of the protonated form of 4, the
pronounced shoulder seen at 530 nm is assigned to an
intramolecular CT transition, while the lowest energy
absorption band centered around 560 nm can be attributed
to the BODIPY S0 fS1 (ππ*) transition.
Figure 3. Cyclic voltammograms in dichloromethane at rt for
5 (red) and 7 (dark blue). Potentials were standardized using
added ferrocene (Fc) as an internal reference.
Table 2. Selected Electrochemical Dataa
dye
E°ox [V] (ΔE° [mV])
E°red [V] (ΔE° [mV])
For the TCBD dye 7, the absorption spectra show a
large broad band between 500 and 800 nm, with a max-
imum centered at 600 nm (ε ≈ 45000 Mꢀ1 cmꢀ1). Weak
solvatochromism is observed in solvents with higher dipole
moments. Upon protonation, a hypsochromic shift of
about 20 nm is observed in all solvents. In all cases, the
fluorescence of the chromophore is completely quenched,
probablyduetoa photoinducedoxidative electrontransfer
(PET) from the BODIPY* to the cyano residue.18 A strong
driving force of ΔG0 ≈ ꢀ720 meV has been calculated
using the RehmꢀWeller equation and by disregarding the
electrostatic effects.19 The optical transition E00 ≈ 2.08 eV
has been estimated using the absorption profile and the
steady state emission of the analogous derivative 5.20
The electrochemical properties of 5 and 7 were investi-
gated in deoxygenated CH2Cl2 solution at rt (Figure 3). The
data are shown in Table 2. For 5, on the oxidation scans, two
irreversible steps at þ0.56 and þ0.86 V were observed,
corresponding to successive one-electron oxidations of the
dimethylamino group and the BODIPY core, respectively.
In the reduction scans, the reversible step at ꢀ1.15 V can be
attributed to the one-electron reduction of the BODIPY
core.21 For 7, interestingly, the oxidation scans show two
reversible steps at þ0.72 and þ1.04 V corresponding to the
oxidation of the dimethylamino group and BODIPY moi-
ety, respectively. The presence of the TCBD group makes the
5
7
þ0.56 (irrev); þ0.86 (irrev) ꢀ1.15 (70)
þ0.72 (70); þ1.04 (70) ꢀ0.32 (70); ꢀ0.78 (60) ;-1.50 (60)
a Cyclic voltammetry carried out in deoxygenated CH2Cl2 solutions,
containing 0.1 M TBAPF6, at a solute concentration range of 1.5 ꢁ 10ꢀ3
M, at 20 °C. Potentials were standardized using added ferrocene (Fc) as an
internal reference and convertedtoSCEassumingthatE1/2 (Fc/Fcþ) =þ0.38
V(ΔEp = 70 mV) versus SCE. Error in half-wave potentials is (15 mV. When
the redox process is irreversible, the peak potential (Eap or Ecp) is quoted.
oxidation of the amino group and BODIPY core more
difficult by 160 and 180 meV, respectively. In the reduction
scans, three well-resolved reversible steps were observed,
corresponding to two successive one-electron reductions of
the two dicyanovinyl (DCV) moieties at ꢀ0.32 V and ꢀ0.78
V and the third reversible one-electron reduction of the
BODIPY moiety at ꢀ1.50 V. The reduction of the BODIPY
core is more difficult by 350 meV due to the successive
reduction of the TCBD residues.
In short, we have succeeded in the regioselective prepara-
tion of monostyryl derivatives and the selective addition of
TCNE on the triple bond side. The interesting electroche-
mical properties, strong CT absorption band in the 500ꢀ700
nm range, and good solubility in common solvents, make the
TCBD/BODIPY dye 7 an interesting candidate for incor-
poration in optoelectronic devices. Further investigations
concerning generalization of the synthetic methods and
applications to solar cells are currently in progress.
(18) (a) De Silva, A. P.; Gunaratne, H. Q. N.; McCoy, C. P. J. Am.
Chem. Soc. 1997, 119, 7891. (b) Coskun, A.; Deniz, E.; Akkaya, E. U.
Org. Lett. 2005, 7, 5187. (c) Fox, M. A. Photochem. Photobiol. 1990, 52,
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2006, 71, 3093.
Acknowledgment. We acknowledge the CNRS for pro-
vision of research facilities and financial support and
Professor Jack Harrowfield (ISIS in Strasbourg) for com-
menting on the manuscript before publication.
(21) (a) Goze, C.; Ulrich, G.; Ziessel, R. J. Org. Chem. 2007, 72, 313.
(b) Nepomnyashchii, A. B.; Cho, S.; Rossky, P. J.; Bard, A. J. J. Am.
Chem. Soc. 2010, 132, 17550.
Supporting Information Available. Synthetic procedures
and analytical data reported herein (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
(22) Olmsted, J. J. Phys. Chem. 1979, 83, 2581.
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