Synthesis and optical properties of imidazole-based fluorophores having high quantum yields

Article abstract of DOI:10.1002/cplu.201300413

A series of 1,4-phenylene-spaced bis-imidazoles with fluorescence quantum yields up to 0.90 and large Stokes shifts have been designed and synthesized using recently developed regioselective direct CH arylation protocols. All the fluorophores show a bright blue-green emission that is well retained in the solid state. DFT calculations attributed their excellent luminescence properties to the significant planarization of the molecules in the equilibrium structures of their excited electronic states.

Full text of DOI:10.1002/cplu.201300413

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DOI: 10.1002/cplu.201300413
Synthesis and Optical Properties of Imidazole-Based
Fluorophores having High Quantum Yields
Marco Lessi,[a] Chiara Manzini,[a] Pierpaolo Minei,[b] Luca A. Perego,[a, b] Julien Bloino,[b, c]
Franco Egidi,[b] Vincenzo Barone,[b] Andrea Pucci,*[a] and Fabio Bellina*[a]
A series of 1,4-phenylene-spaced bis-imidazoles with fluores-
cence quantum yields up to 0.90 and large Stokes shifts have
been designed and synthesized using recently developed re-
gioselective direct CH arylation protocols. All the fluorophores
show a bright blue-green emission that is well retained in the
solid state. DFT calculations attributed their excellent lumines-
cence properties to the significant planarization of the mole-
cules in the equilibrium structures of their excited electronic
states.
character, transition-metal-binding activity, thermal and chemi-
cal robustness, and tautomerism, and has found diverse appli-
cations in ionic liquids, ligands, and drugs. Moreover, imidazole
and benzimidazole moieties have been utilized as suitable p-
conjugated spacers in charge-transfer chromophores and
useful DNA-binding probes for fluorescence microscopy and
flow cytometry.[10,11]
To the best of our knowledge, no published study has been
performed on unsymmetrically substituted p-phenylene-linked
bis-imidazoles. Nevertheless, they seem promising in terms of
optical properties, such as large Stokes shifts and high fluores-
cence quantum yields, as can be inferred by comparison with
similar compounds (e.g., 1,4-bis(5-phenyl-2-oxazolyl)benzene
(POPOP) derivatives) already described in the literature.[12]
Moreover, unsymmetrical derivatives are likely to have en-
hanced charge transfer upon excitation in comparison to sym-
metrical compounds.
Heteroaromatic fluorophores with electron-donor and -accept-
or architectures have attracted growing interest for both the
understanding of fundamental chemistry and physics and
promising applications in diverse fields, ranging from solar
energy conversion[1] to optoelectronic devices[2] and chromo-
genic materials.[3,4] Recently, it has also been recognized that
the use of suitable heteroaromatic backbones usually increases
the polarizability, stability, and thermal and chemical robust-
ness required for fabrication processes. Notably, an impressive
amount of attention has been devoted to the development of
various organic p-conjugated compounds because of their
highly polarizable structures and resulting efficient intramolec-
ular charge transfer.[5,6] The polarizability of these systems de-
pends primarily on their chemical structures, and in particular
on the donors and acceptors and on the length and nature of
the p-conjugated bridge.[1,5,6] In contrast to inorganic materials,
organic materials with readily polarizable push–pull systems
have also been recognized as tunable fluorophores for nonlin-
ear optics.[7–9]
The work reported herein concerns the application of palla-
dium-catalyzed selective direct CꢀH arylation reactions to the
synthesis of novel fluorophores 1a–c (Scheme 1) featuring
Scheme 1. Chemical structures of compounds 1a–c.
a 1,4-phenylene-linked bis-imidazole scaffold, which display in-
teresting spectroscopic properties such as high Stokes shifts
and relevant fluorescence quantum yields. Interestingly, recent
advances in transition-metal-catalyzed direct CꢀH arylation of
heterocycles, which offers an alternative reliable method to
classical cross-coupling methodology,[13–19] have been little ex-
ploited to design neat syntheses of heterocyclic fluoro-
phores.[10,20–24] We selected a methoxy, a methyl, and a cyano
group as substituents on the terminal phenyl ring of 1, since
they are typical examples of electron-releasing, electron-neu-
tral, and electron-withdrawing groups, respectively (Hammett’s
sp constants:[25] CN +0.66; Me ꢀ0.17; MeO ꢀ0.27). For this
reason, they are likely to be representative of other similar sub-
stituents as concerns both synthetic issues and spectroscopic
properties.
As far as heteroaromatics are concerned, imidazole possess-
es a wide range of interesting properties, such as acid–base
[a] M. Lessi, C. Manzini, L. A. Perego, Dr. A. Pucci, Prof. F. Bellina
Dipartimento di Chimica e Chimica Industriale
Universitꢀ di Pisa
Via Risorgimento 35, 56126 Pisa (Italy)
E-mail: andrea.pucci@unipi.it
fabio.bellina@unipi.it
[b] P. Minei, L. A. Perego, J. Bloino, F. Egidi, Prof. V. Barone
Classe di Scienze
Scuola Normale Superiore
Piazza dei Cavalieri 7, 56126 Pisa (Italy)
[c] J. Bloino
Istituto di Chimica dei Composti Organometallici
Consiglio Nazionale per le Ricerche
Area della Ricerca, via Moruzzi 1, 56125 Pisa (Italy)
Compounds 1a–c were synthesized according to a simple
and scalable synthetic procedure involving two sequential pal-
ladium-catalyzed regioselective direct CꢀH arylation reactions
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cplu.201300413.
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amount of light absorbed and
the quantum efficiency of the
fluorophore. B values of around
30000mꢀ1 cmꢀ1 are among the
highest calculated for fluoro-
phores in the same wavelength
region (for example, pyrene
brightness=32000mꢀ1 cmꢀ1).[28]
Compounds 1a–c
showed
a polarity-dependent change in
the fluorescence spectral proper-
Scheme 2. Synthesis of fluorophores 1a–c. DMA=N,N-dimethylacetamide.
starting from 1-methyl-1H-imidazole (2; Scheme 2). In detail,
5-aryl-1-methyl-1H-imidazoles 4a–c were prepared efficiently
by a palladium-catalyzed direct C5ꢀH arylation reaction, pro-
moted by Bu4NOAc, involving 2 and aryl bromides 3a–c as de-
scribed recently by us.[26] The 5-arylimidazoles 4a–c so ob-
tained were then reacted with 2-(4-bromophenyl)-1-methyl-1H-
benzimidazole (5) according to our recent protocol for the pal-
ladium- and copper-promoted regioselective direct C2ꢀH aryla-
tion reaction under base- and ligand-free conditions.[27] Inter-
mediate 5 has been obtained by the condensation of 4-bromo-
benzaldehyde with N-methyl-1,2-benzenediamine and oxida-
tion (see the Supporting Information). In this way, the required
fluorophores 1a–c were isolated in 42–88% yield. All the inter-
mediates and products were characterized by NMR spectrosco-
py and mass spectrometry, with satisfactory results.
Figure 1. Absorbance (left) and emission (right) spectra of 5 mm dye solu-
tions in THF.
All the optical features of compounds 1a–c are summarized
in Table 1. Notably, the absorption spectrum of derivatives 1a
and 1b are practically the same, whereas 1c shows an absorp-
tion band about 10 nm redshifted (Figure 1).
ties when dissolved in MeOH (Figure S2, see the Supporting In-
formation). The fluorescence peaks redshifted about 15 nm
from THF to MeOH solutions, thus indicating that the fluores-
cent states of the dyes are of intramolecular charge-transfer
character.
It is also reported that the intensity of fluorescence emission
If observed at a wavelength lf should vary with the concentra-
tion c of the emitting species according to Equation (1):[29]
Table 1. Spectroscopic properties of fluorophores 1a–c dissolved in THF.
labs [nm] e [mꢀ1 cmꢀ1
]
lem [nm] S [cmꢀ1
]
Ff[a] B [mꢀ1 cmꢀ1
]
[b]
Â
Ã
If ¼ kðlfÞIoðleÞ 1 ꢀ 10ꢀeðl Þlc
e
ð1Þ
1a 325
36000
31000
39000
428
415
397
7406
7154
2980
0.90 32400
0.88 27280
0.83 32370
1b 320
1c 335
in which k is a proportionality constant that depends on ex-
perimental conditions, Io is the intensity of the incident light at
the wavelength le, l is the path length, and e the molar extinc-
tion coefficient. The fluorescence intensity is thus expected to
increase with concentration but only for absorbances usually
less than 0.1. Deviations from a linear behavior occur at higher
absorbances for a variety of reasons, among which radiative
transfer phenomena or the formation of aggregates are the
most representative.[29] Compounds 1a–c start to display self-
[a] Fluorescence quantum yield (F) was determined relative to quinine
sulfate in 0.1m H2SO4 (F=0.54). [b] The brightness (B) of fluorophores is
calculated as the product of the absorption coefficient e and F.
The emission spectrum becomes progressively redshifted in
the order 1c, 1b, 1a, and the Stokes shift (S) thus increases in
the same direction (Figure 1). The fluorescence quantum yields
(F) of the three fluorophores were also determined to have
a quantitative picture (Table 1). All molecules were strong emit-
ters with quantum yields between 83 and 90%. The lowest
F value corresponds to 1c, which is characterized by the
lowest S value (2980 cmꢀ1 =62 nm) and the highest overlap-
ping between absorbance and emission (Figure 1). The prod-
uct of e and F was also calculated for making comparisons be-
tween the different fluorophores. This parameter is defined as
the brightness (B) of the dye, which accounts for both the
quenching properties for concentrations higher than 10ꢀ5
m
(absorbances of about 0.30–0.35), as reported in Figure S2.
Nevertheless, all fluorophores exhibit bright blue-green emis-
sions in the solid state as well (Figures 2 and 3). Powders of 1b
and 1c emit significantly redshifted fluorescence relative to 1a
and THF solutions. This phenomenon may be attributed to the
higher electronic coupling resulting from aggregation of their
respective molecules or planarization of their chromophore
backbone owing to the increased conjugation.
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Figure 2. Normalized emission spectra of solid dyes 1a–c.
Figure 3. Pictures of the different solid samples taken under illumination at
366 nm.
Theoretical calculations at the (time-dependent)-DFT/CAM-
B3LYP/N07D/PCM level of theory were also performed to
better understand the peculiar photophysical properties of
1a–c (see the Supporting Information). Some qualitative in-
sights can be gained by inspection of frontier molecular orbital
(MO) graphical representations, since the observed band is
almost entirely a result of HOMO–LUMO transition, as can be
inferred by inspection of the configuration interaction expan-
sion coefficients. The MO isosurfaces of compounds 1a and
1c, that is, those bearing respectively the electron-releasing
and electron-withdrawing groups, are reported in Figures 4
and 5. For both 1a and 1c the HOMO is spread approximately
equally all over the molecule, but the appearance of the LUMO
is very different between the two compounds.
Figure 5. MO surfaces for 1c. Bottom: HOMO (ground-state geometry)
Middle: LUMO (ground-state geometry). Top: LUMO (excited-state optimized
geometry).
For 1a there is a significant charge transfer from the me-
thoxy-substituted phenyl ring towards the benzimidazole nu-
cleus. For 1c the charge transfer is in the opposite direction
and goes from the benzimidazole moiety to the CN-substitut-
ed phenyl ring. Dipole moments are clearly higher in the excit-
ed state than in the ground state for both 1a (4.75 and 3.46 D,
respectively) and 1c (5.82 and 5.05 D, respectively) and are in
approximately opposite directions, as depicted in Figure S3.
Most interestingly, we observed that geometry optimization of
the excited electronic states makes the individual rings signifi-
cantly more coplanar in both cases (computed dihedral angles
are shown in Scheme 3) and the charge transfer is attenuated.
Figure 4. MO surfaces for 1a. Bottom: HOMO (ground-state geometry).
Middle: LUMO (ground-state geometry). Top: LUMO (excited-state optimized
geometry).
Scheme 3. Dihedral angles for compounds 1a and 1c. Values after excited-
state geometry optimization are reported in parentheses.
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The significant planarization of the molecule in the equilibrium
structure of the excited electronic state is a consistent explana-
tion of the high Stokes shifts observed, as already reported in
the literature for analogous POPOP-type dyes.[30] Moreover, the
higher planarization shown by 1c relative to 1a possibly ex-
plains its redshifted emission in the solid state.
2-{4-[5-(4-Methoxyphenyl)-1-methyl-1H-imidazol-2-yl]phen-
yl}-1-methyl-1H-benzo[d]imidazole (1a)
The reaction between 5 and 4a according to the general proce-
dure (72 h) gave 1a in the form of an off-white amorphous solid
(195.1 mg, 66%). M.p. 266–2698C; 1H NMR (200 MHz, CDCl3): d=
7.89–7.82 (m, 5H), 7.42–7.31 (m, 5H), 7.19 (s, 1H), 7.01 (d, J=
8.5 Hz, 2H), 3.93 (s, 3H), 3.87 (s, 3H), 3.72 ppm (s, 3H); 13C NMR
(50.3 MHz, CDCl3): d=159.6, 153.2, 148.0, 143.0, 136.7, 135.9, 132.3,
130.2, 129.5, 129.3, 128.7, 128.4, 127.4, 123.0, 122.6, 120.4, 119.9,
119.5, 114.3, 109.6, 55.6, 34.0, 29.7 ppm; EI-MS: m/z (%): 395 (27),
394 (100, M+), 393 (51); elemental analysis calcd (%) for C25H22N4O:
C 76.12, H 5.62; found: C 76.63, H 5.58.
In conclusion, highly efficient access to a set of 1,4-phenyl-
ene-linked bis-imidazole fluorophores is reported, which takes
advantage of sequential regioselective palladium-catalyzed
direct arylation reactions starting from 1-methyl-1H-imidazole
(2). Compounds 1a–c showed in solution Stokes shifts up to
103 nm, very high fluorescence quantum yields, and their
bright blue-green emission was well retained in the solid state.
Quantum mechanical calculations at the DFT level suggested
that the excellent luminescence properties of this class of com-
pounds result from the more planar structure of the chromo-
phoric units in the excited electronic state.
1-Methyl-2-[4-(1-methyl-5-p-tolyl-1H-imidazol-2-yl)phenyl]-
1H-benzo[d]imidazole (1b)
The reaction between 5 and 4b according to the general proce-
dure (92 h) gave 1b in the form of an off-white amorphous solid
(250.8 mg, 88%). M.p. 249–2528C; 1H NMR (200 MHz, CDCl3): d=
7.93–7.82 (m, 5H), 7.44–7.28 (m, 7H), 7.23 (s, 1H), 3.92 (s, 3H), 3.73
(s, 3H), 2.42 ppm (s, 3H); 13C NMR (50.3 MHz, CDCl3): d=153.3,
143.2, 138.3, 136.9, 136.3, 132.3, 130.5, 129.9, 129.1, 128.9, 127.7,
127.3, 123.2, 122.8, 120.2, 109.9, 34.2, 32.1, 21.6 ppm; EI-MS: m/z
(%): 379 (25), 378 (M+, 100), 377 (66); elemental analysis calcd (%)
for C25H22N4: C 79.34, H 5.86; found: C 79.01, H 5.89.
These findings could be exploited quite reliably for the reali-
zation of a large library of luminescent dyes with near-unity
fluorescence quantum yields able to emit in the visible–near-IR
optical region.
Experimental Section
General procedure for the synthesis of 2-[4-aryl-(1-methyl-
1H-imidazol-2-yl)phenyl]-1-methyl-1H-benzo[d]imidazoles
1a–c
4-{1-Methyl-2-[4-(1-methyl-1H-benzo[d]imidazol-2-yl)phen-
yl]-1H-imidazol-5-yl}benzonitrile (1c)
The reaction between 5 and 4c according to the general proce-
dure (92 h) gave 1c in the form of off-white amorphous solid
(122.7 mg, 42%). M.p. 279–2828C; 1H NMR (200 MHz, CDCl3): d=
7.96–7.75 (m, 7H), 7.60 (d, J=8.3 Hz, 1H), 7.44–7.33 (m, 4H), 3.93
(s, 3H), 3.77 ppm (m, 3H); 13C NMR (50.3 MHz, CDCl3): d=153.0,
150.3, 143.1, 136.9, 134.7, 134.4, 133.0, 131.7, 131.1, 130.0, 129.8,
129.3, 128.7, 123.4, 122.9, 120.1, 118.8, 111.6, 110.0, 34.6, 32.2 ppm;
EI-MS: m/z (%): 391 (4), 389 (M+, 100), 388 (83); elemental analysis
calcd (%) for C25H19N5: C 77.10, H 4.92; found: C 76.96, H 4.96.
A two-necked flask equipped with a magnetic stirrer and a reflux
condenser was charged with the appropriate 5-aryl-1-methyl-1H-
imidazole 4a–c[26] (0.75 mmol), 2-(4-bromophenyl)-1-methyl-1H-
benzo[d]imidazole 5 (323.0 mg, 1.13 mmol), Pd(OAc)2 (8.4 mg,
0.04 mmol), and CuI (285.7 mg, 1.50 mmol). The apparatus was
closed with a silicone septum, evacuated, and back-filled with
argon. The latter procedure was repeated three times. Anhydrous
N,N-dimethylacetamide (4.0 mL) was added by syringe against
a positive pressure of argon. The reaction mixture was stirred at
1608C. The degree of completion of the reaction and the composi-
tion of the reaction mixture were established on the basis of GLC
and GLC-MS analyses of samples of the crude reaction mixtures di-
luted with CH2Cl2 and washed with saturated NH4Cl solution to
which a few drops of concentrated aqueous ammonia had been
added. After cooling to room temperature, the reaction mixture
was diluted with CH2Cl2 and poured into a saturated aqueous
NH4Cl solution, and the resulting mixture was stirred in the open
air for 0.5 h and then extracted with CH2Cl2. The organic extracts
were washed with saturated brine, dried, filtered over Celite, and
the filtrate was concentrated under reduced pressure. The residue
was purified by flash chromatography on silica gel with a mixture
of CH2Cl2/MeOH (95:5) as eluent. The chromatographic fractions
containing the required compound were collected and concentrat-
ed under reduced pressure. The solid compound so obtained
was triturated with Et2O, isolated by filtration, and dried under
vacuum. This procedure[31] was employed to prepare com-
pounds 1a–c (Scheme 2).
Acknowledgements
This study was supported by the Fondazione Pisa under “POLOP-
TEL” (project no. 167/09) and by MIUR-FIRB (RBFR122HFZ).
Keywords: arylation
calculations · fluorescence · imidazoles
·
CꢀC coupling
· density functional
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