Synthesis of a non-aggregating bay-unsubstituted perylene bisimide dye with latent bromo groups for C-C cross coupling

Article abstract of DOI:10.1021/ol401946g

To address the absence of synthetic routes to access easily functionalizable, non-aggregating, and soluble bay-unsubstituted perylene bisimide dyes, an efficient, three-step, multigram-scale synthesis of the divergent building block N,N′-bis(4-bromo-2,6-diisopropylphenyl)perylene- 3,4:9,10-tetracarboxylic bisimide is reported. Suzuki coupling yields new dyes that maintain excellent solubility and exhibit unity quantum yields in CHCl ₃, THF, toluene, and CH₃CN. The methodology reported here enables access to dyes with sensitive functional groups such as aldehydes that are not accessible by traditional imidization routes.

Full text of DOI:10.1021/ol401946g

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Synthesis of a Non-aggregating
Bay-Unsubstituted Perylene Bisimide
Dye with Latent Bromo Groups for
CꢀC Cross Coupling
€
Peter D. Frischmann and Frank Wurthner*
€
Universitat Wurzburg, Institut fur Organische Chemie, Am Hubland,
97074 Wu€rzburg, Germany
€
€
wuerthner@chemie.uni-wuerzburg.de
Received July 10, 2013
ABSTRACT
To address the absence of synthetic routes to access easily functionalizable, non-aggregating, and soluble bay-unsubstituted perylene bisimide
dyes, an efficient, three-step, multigram-scale synthesis of the divergent building block N,N0-bis(4-bromo-2,6-diisopropylphenyl)perylene-
3,4:9,10-tetracarboxylic bisimide is reported. Suzuki coupling yields new dyes that maintain excellent solubility and exhibit unity quantum yields
in CHCl3, THF, toluene, and CH3CN. The methodology reported here enables access to dyes with sensitive functional groups such as aldehydes
that are not accessible by traditional imidization routes.
Perylene bisimides (PBIs) constitute a class of multi-
functional dyes characterized by their intense visible-light
absorption, chemical- and photostability, electron-accepting
ability, and unity quantum yields.1 Because of these desir-
able properties, PBI dyes have proven useful for a variety
of applications ranging from industrial color pigments to
active layers in organic field-effect transistors (OFET) and
photovoltaic cells (OPV).2 The large planar π-conjugated
core of PBI that is responsible for many of PBIs advanta-
geous properties also drives self-aggregation of PBI dyes,3
frequently resulting in luminescence quenching and poor
solubility.1 Although controlled aggregation of dyes is
desirable for some light-harvesting applications such as
the self-assembly of charge conduits,4 luminescent J-type
aggregates,5 and for OPV applications due to excitonic
coupling that results in broadened absorption bands,6 dyes
that limit or entirely prohibit self-aggregation are valuable
for persistent fluorescence at high concentration or in the
(1) (a) Huang, C.; Barlow, S.; Marder, S. R. J. Org. Chem. 2011, 76,
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2386. (b) Weil, T.; Vosch, T.; Hofkens, J.; Peneva, K.; Mullen, K. Angew.
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88, 1309. (d) Wurthner, F. Chem. Commun. 2004, 1564.
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Beckers, E. H. A.; Meskers, S. C. J.; Schenning, A. P. H. J.; Chen, Z.;
(2) (a) Mei, J.; Diao, Y.; Appleton, A. L.; Fang, L.; Bao, Z. J. Am.
Chem. Soc. 2013, 135, 6724. (b) Li, C.; Wonneberger, H. Adv. Mater.
2012, 24, 613. (c) Zhan, X.; Facchetti, A.; Barlow, S.; Marks, T. J.;
Ratner, M. A.; Wasielewski, M. R.; Marder, S. R. Adv. Mater. 2011, 23,
268. (d) Zollinger, H. Color Chemistry, 3rd ed.; VHCA and Wiley-VCH:
Z€urich, Weinheim, 2003.
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Wurthner, F.; Marsal, P.; Beljonne, D.; Cornil, J.; Janssen, R. A. J.
J. Am. Chem. Soc. 2006, 128, 649. (c) Schenning, A. P. H. J.; Meijer,
E. W. Chem. Commun. 2005, 3245.
€
€
(5) Wurthner, F.; Kaiser, T. E.; Saha-Moller, C. R. Angew. Chem.,
Int. Ed. 2011, 50, 3376.
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(3) Chen, Z.; Fimmel, B.; Wurthner, F. Org. Biomol. Chem. 2012, 10,
5845.
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F.; Bauer, C.; Stepanenko, V.; Yagai, S. Adv. Mater. 2008, 20, 1695.
r
10.1021/ol401946g
XXXX American Chemical Society

solid-state,7 asprobesfor single-moleculespectroscopy,1b,8
for constructing discrete metallosupramolecular light-
harvesting antennae and photosensitizers,9 and for incorpora-
tion in polymers with n-type semiconducting or fluorescent
properties.10 In addition, limiting aggregation of PBI accep-
tors in donorꢀacceptor films was shown to improve film
morphology and promote charge-separation for OPV
applications.11
of bay substituents results in a twisting of the PBI core that
broadens the otherwise sharp vibronic bands, red-shifts the
absorption maximum, alters the redox chemistry, and
introduces atropisomerism into the system.1,12,13 Indepen-
dently, Langhals and Graser have introduced bulky sub-
stituents at the imide position of bay-unsubstituted PBIs to
access highly soluble, non-aggregating dyes such as 2aꢀd
depicted in Figure 1.7 Although these dyes minimize or
prevent aggregation-driven fluorescence quenching, they
lack sufficient handles for further synthetic modification.
Surprisingly, there is a profound absence of synthetic
routes to bay-unsubstituted PBI dyes that both persist in
a non-aggregated state at high concentration and may be
further synthetically manipulated to introduce desirable
functional groups. In addition, because of the harsh con-
ditions involved in standard imidization methods (e.g.,
moltenimidazole), it isnearly impossible toinstall sensitive
functional groups on bay-unsubstituted PBI derivatives.
To address these shortcomings, we report here the multigram-
scale synthesis of a synthetically tractable, bay-unsubstituted
PBI scaffold that is both monomeric at high concentration
and may be easily manipulated via modern CꢀC cross
coupling chemistry to introduce desirable functional groups.
PBI 3 (Scheme 1), a bromo-functionalized derivative of
2a, was identified as a suitable bay-unsubstituted target
because of its lack of atropisomerism (observed for 2b)14
and defined geometry upon substitution. Imidization of
perylene-3,4:9,10-tetracarboxylic bisanhydride (PBA)
with 2,6-diisopropylaniline yielded 2a in 66% yield after
heating the mixture at 190 °C for 24 h in imidazole.11
Screening the same imidization conditions with 4-bromo-
2,6-diisopropylaniline (4) gave virtually no product. A
wide breadthof standardPBA imidization conditions were
tested such as imidazole/Zn(II) at 140 °C, m-cresol/quinoline
at 185 °C, quinoline/Zn(II) at 200 °C, refluxing propionic
acid, as well as base-promoted direct coupling of N-(4-
bromo-2,6-diisopropylphenyl)-1,8-naphthalimide.15 In no
instance was the desired PBI 3 obtained in >5% yield, and
often no product was detectedevenwhena large excess of 4
was used (up to 20 equiv). The best caveat for the lack of
reactivity is the juxtaposition of low PBA solubility and
poor nucleophilicity of 4 due to the combined effects of the
bulky 2,6-diisopropyl substituents and the electron-with-
drawing nature of the bromo group.
Figure 1. Structures of known PBI dyes 1a, 1b, and 2aꢀd that
exhibit limited aggregation and near-unity fluorescence quan-
tum yields even at high concentration.
Recent efforts in PBI synthesis have focused on the
introduction of bay substituents such as aryloxy groups
at the 1,6,7,12-positions to impart solubility and limit
aggregation while leaving the imide positions available
for further functionalization (Figure 1, 1a and 1b).12 From
a synthetic perspective, bay-substituted PBIs are generally
favored over bay-unsubstituted PBIs because introducing
structural diversity is limited to the imide positions of
unsubstituted PBIs, where a compromise must be reached
between substituents that impart sufficient solubility and
function. Despite the ability ofbaysubstituents to limit dye
aggregation, at high concentrations and in certain solvents
aggregation is still observed.12 Additionally, introduction
To overcome the lack of reactivity with PBA, a more
soluble PBI precursor, tetramethyl 4,40-binaphthyl-1,10,-
8,80-tetracarboxylate (5), was synthesized to replace PBA
(Scheme 1).16 The improved solubility of 5 compared to
PBA in molten imidazole enabled highly efficient imidiza-
tion with only three equivalents of 4 in the presence of
ZnCl2 yielding 6 in excellent yield (99%). Adapting a
€ €
(7) (a) Langhals, H.; Ismael, R.; Yuruk, O. Tetrahedron 2000, 56,
5435. (b) Rademacher, A.; Markle, S.; Langhals, H. Chem. Ber. 1982,
115, 2927. (c) Graser, F. Perylenetetracarboxylic acid diimides and their
use. US Patent 4446324, May 1, 1984.
(8) Jung, C.; Ruthardt, N.; Lewis, R.; Michaelis, J.; Sodeik, B.;
€
€
€
Nolde, F.; Peneva, K.; Mullen, K.; Brauchle, C. ChemPhysChem 2009,
10, 180.
€
(9) Frischmann, P. D.; Mahata, K.; Wurthner, F. Chem. Soc. Rev.
2013, 42, 1847.
€
procedure reported by Mullen and co-workers used to
(10) (a) Schubert, M.; Dolfen, D.; Frisch, J.; Roland, S.; Steyrleuthner,
R.; Stiller, B.; Chen, Z.; Scherf, U.; Koch, N.; Facchetti, A.; Neher, D.
Adv. Energy Mater. 2012, 2, 369. (b) Baier, M. C.; Huber, J.; Mecking, S.
J. Am. Chem. Soc. 2009, 131, 14267. (c) Matthews, J. R.; Goldoni, F.;
Schenning, A. P. H. J.; Meijer, E. W. Chem. Commun. 2005, 5503. (d)
Nguyen, T.-Q.; Martini, I. B.; Liu, J.; Schwartz, B. J. J. Phys. Chem. B
2000, 104, 237.
access extended rylene dyes,17 N,N0-bis(4-bromo-2,6-
diisopropyl)-4,40-binaphthyl-1,10,8,80-teracarboxylic bisi-
mide 6 was oxidatively aromatized in ethanolamine with
€
(13) Osswald, P.; Wurthner, F. J. Am. Chem. Soc. 2007, 129, 14319.
(14) Langhals, H. Chem. Ber. 1985, 118, 4641.
(15) Sakamoto, T.; Pac, C. J. Org. Chem. 2001, 66, 94.
(16) Li, N.; Cui, Z.; Zhang, S.; Xing, W. Polymer 2007, 48, 7255.
(11) Ramanan, C.; Smeigh, A. L.; Anthony, J. E.; Marks, T. J.;
Wasielewski, M. R. J. Am. Chem. Soc. 2012, 134, 386.
€
(12) Wurthner, F. Pure Appl. Chem. 2006, 78, 2341.
B
Org. Lett., Vol. XX, No. XX, XXXX

K2CO3 at 100 °C. Purification by filtration gave target PBI
3 in good yield on a 16-g scale (60%).18 Remarkably, no
column chromatography is required over the three-step
synthesis (47% overall).
Scheme 1. Synthesis of PBI 3
Figure 2. Molecular structure of PBI 3 in single crystals grown
from toluene. (a) Top-down view of the PBI core highlighting
the perpendicular arrangement of the 4-bromo-2,6-diisopropyl-
phenyl imide substituents. (b) View down the b-axis showing the
cocrystallized toluene molecules located between PBI π-surfaces.
The other two unique toluene environments have been omitted for
clarity (C = green, N = blue, O = red, Br = yellow, H = white).
are depicted in Figure 2. Suitable crystals were grown by
slow evaporation of a toluene solution of 3 which crystal-
lized in the monoclinic space group P21/c.19 The 4-bromo-
2,6-diisopropylphenylimide substituents are arranged per-
pendicular to the planar PBI core, effectively preventing
intermolecular πꢀπ stacking of the PBI dyes. Because the
bulky imide substituents prohibit close contacts between
the PBI π-scaffolds, each unit cell contains roughly eight
cocrystallized toluene molecules in three unique orienta-
tions. One toluene molecule is located directly between two
PBI π-surfaces (PBIꢀtoluene and PBIꢀPBI πꢀπ distance
˚
∼3.5 and 7.0 A, respectively). The other two unique cocrys-
tallized toluene molecules are located out of the plane of the
tolueneꢀPBI stack (Figure 2b) forming a pseudolamellar
organization of the PBI dyes and cocrystallized toluene
(Supporting Information, Figure S14). PBI 3 is emissive in
the solid state (λabs = 643 nm, ΦF = 0.067).
To demonstrate the utility of 3 as a divergent building
block for accessing soluble, non-aggregating, bay unsub-
stituted PBIs, we synthesized dipyridyl- and dialdehyde-
substituted derivatives by subsequent Suzuki coupling
(Scheme 2). Bay-substituted derivatives of PBI with 4-pyr-
idyl groups at the imide positions have been successfully
organized into light-harvesting and photosensitizing
macrocycles, cages, and triads by coordination-driven self-
assembly.20 To maximize the performance of photofunc-
tional supramolecules for light-harvesting applications, the
1
The H NMR spectrum of 3 in CDCl3 reveals a high-
symmetry molecule withtwo aromatic resonances found at
8.81 and 8.77 ppm corresponding to the PBI core protons,
a singlet at 7.48 ppm from the aromatic protons on the
imide phenyl ring, a septet at 2.74ppm from the protons on
the tertiary carbon of the i-Pr substituents, and a doublet
from the methyl groups of the i-Pr substituents at 1.19 ppm
(Supporting Information, Figure S1). The identity of 3 was
further confirmed by standard techniques (Supporting
Information). Dye 3 exhibits reasonable to excellent solu-
bility in a range of solvents such as CHCl3, toluene, THF,
DMSO, DMF, and MeOH.
(19) X-ray crystal data for 3: C48H40Br2N2O4 (C7H8)2, monoclinic,
3
˚
space group P21/c, a = 17.341(1) A, b = 17.764(1) A, c = 17.827(1) A,
˚
˚
The solid-state packing of PBI 3 was elucidated by
single-crystal X-ray diffraction (SCXRD), and the results
3
V = 4948.3(5) A , Z = 4, R1 = 0.0393, wR2 = 0.0983.
˚
(20) (a) Indelli, M. T.; Chiorboli, C.; Scandola, F.; Iengo, E.;
€
Osswald, P.; Wurthner, F. J. Phys. Chem. B 2010, 114, 14495. (b)
Sautter, A.; Kaletas-, B. K.; Schmid, D. G.; Dobrawa, R.; Zimine, M.;
€
(17) Nolde, F.; Qu, J.; Kohl, C.; Pschirer, N. G.; Reuther, E.; Mullen,
K. Chem.;Eur. J. 2005, 11, 3959.
(18) PBI 3 has been claimed in a patent: Chen, R. Perylene diimide
photoelectric functional materials and preparation method thereof.
Patent CN 102070771 A, May 25, 2011. However, no synthetic procedures
or characterization beyond a 1H NMR spectrum are reported.
Jung, G.; van Stokkum, I. H. M.; De Cola, L.; Williams, R. M.;
€
Wurthner, F. J. Am. Chem. Soc. 2005, 127, 6719. (c) Prodi, A.;
Chiorboli, C.; Scandola, F.; Iengo, E.; Alessio, E.; Dobrawa, R.;
€
Wurthner, F. J. Am. Chem. Soc. 2005, 127, 1454. (d) Addicott, C.;
€
Oesterling, I.; Yamamoto, T.; Mullen, K.; Stang, P. J. J. Org. Chem.
2005, 70, 797.
Org. Lett., Vol. XX, No. XX, XXXX
C

Table 1. Solubility and Photophysical Properties of 7 in Selected
Solvents
Scheme 2. Synthesis of Dipyridyl (7) and Dialdehyde (8) Sub-
stituted PBI Dyes from 3
solvent
solubility (g Lꢀ1
)
λabs (nm)
λF (nm)
ΦF
CHCl3
THF
>59a
8.5
529
525
525
529
537
535
535
539
1.00
1.00
1.00
1.00
CH3CN
toluene
0.6
0.3
a Rough estimate due to high solubility.
because the necessary amino-aldehyde building block will
self-condense and may deformylate at the elevated tempera-
tures necessary for PBA imidization. However, 8 is easily
accessed by heating PBI 3, 4-formylphenylboronic acid,
Pd(dppf)Cl2, and aqueous K2CO3 in 1,4-dioxane for 24 h
at 85 °C (Scheme 2). Chromatography yielded 8 in 62%,
and the identity was confirmed by standard techniques
(Supporting Information).
In summary, we have developed an efficient, multigram-
scale synthetic route to dibromo-substituted PBI 3. Two
new functional PBI dyes, 7 and 8, have been isolated by
Suzukicoupling, establishing PBI3 asanexcellentbuilding
block to access soluble, non-aggregating, and highly lumi-
nescent bay-unsubstituted PBI derivatives. Functional
groups that are incompatible with modern imidization
procedures, such as aldehydes, may be accessed using this
route. We anticipate dye 3 will be a valuable divergent
building block for constructing functional PBI dyes using
other CꢀC bond forming protocols such as Stille, Heck,
and Sonogashira coupling. A broad range of polymers
bearing PBI functional units will become accessible as well.
ability to tune the absorption maxima and HOMOꢀLUMO
levels of individual components is highly desirable. There-
fore, dipyridyl-substituted PBI 7 was first targeted. Heat-
ing 3, pyridine-4-boronic acid, Pd(dppf)Cl2, and aqueous
K2CO3 in 1,4-dioxane for 24 h at 80 °C yielded the desired
PBI 7 in 88% after column chromatography. Standard
techniques were applied to confirm the identity of 7
(Supporting Information).
The solubility, aggregation strength, and fluorescence
quantum yield of dipyridyl PBI 7 were measured in CHCl3,
THF, CH3CN, and toluene. These solvents were chosen
because they are common media for studying the photo-
physics of self-assembled systems, in particular, metallo-
supramolecular complexes. The results are summarized in
Table 1. PBI 7 is sufficiently soluble in all four solvents for
spectroscopic investigation and highly soluble in CHCl3 and
THF. Absorption and emission maxima are nearly indepen-
dent of solvent polarity. No aggregation was observed by
UVꢀvis spectroscopy in THF, toluene, and CHCl3 (see the
Supporting Information for details).21 A slight degree of
aggregation was observed in CH3CN at the concentration
limit; however, the aggregation process was too weak to
quantify (Supporting Information Figure S12). Importantly,
unity quantum yields are maintained in all four solvents.
Our second target, PBI 8, has two aldehydes that are
excellent starting points for a variety of organic transfor-
mations and readily undergo reversible condensation with
primary amines and hydrazides, making 8 an interesting
fluorescent probe for dynamic combinatorial chemistry.22
PBI 8 is inaccessible using traditional imidization conditions
Acknowledgment. P.D.F. thanks the Alexander von
Humboldt Foundation for a postdoctoral fellowship. We
€
thank A.-M. Krause and C. Burschka (Universitat
Wurzburg) for the SCXRD analysis. Generous financial
€
support by the Bavarian State Ministry of Science, Research,
and the Arts for the Collaborative Research Network “Solar
Technologies go Hybrid” is gratefully acknowledged.
Supporting Information Available. Experimental pro-
cedures, characterization, and crystallographic details.
This material is available free of charge via the Internet
at http://pubs.acs.org.
(22) (a) Li, J.; Nowak, P.; Otto, S. J. Am. Chem. Soc. 2013, 135, 9222.
(b) Lehn, J.-M. Chem. Soc. Rev. 2007, 36, 151. (c) Corbett, P. T.;
Leclaire, J.; Vial, L.; West, K. R.; Wietor, J.-L.; Sanders, J. K. M.; Otto,
S. Chem. Rev. 2006, 106, 3652.
(21) In CHCl3, the high solubility and large extinction coefficient of 7
.
prevented aggregation studies at concentrations above 3.2 mmol Lꢀ1
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX