Fluorescent 2-(2′-hydroxybenzofuran)benzoxazole (HBBO) borate complexes: Synthesis, optical properties, and theoretical calculations

Article abstract of DOI:10.1016/j.tetlet.2014.06.002

The multi-step synthesis, structural and optical properties of original luminescent borate complexes derived from 2-(2′-hydroxybenzofuran) benzoxazole (HBBO) are reported. Functionalization at position 3 of the benzofuran ring was readily achieved through an electrophilic cyclization key step followed by a Sonogashira cross-coupling reaction. The optical properties of the resulting boron difluoride dyes highlight different photophysical behaviors depending on the nature of the substitution at position 3 of the benzofuran core (^tBu-phenylacetylene or NⁿBu ₂-phenylacetylene). The NⁿBu₂-phenylacetylene moiety favors a sizeable intramolecular charge transfer as evidenced by a strong solvatochromism; a feature further confirmed by ab initio calculations.

Full text of DOI:10.1016/j.tetlet.2014.06.002

Accepted Manuscript
Fluorescent 2-(2’-Hydroxybenzofuran) benzoxazole (HBBO) borate com-
plexes: Synthesis, Optical Properties and Theoretical Calculations
Julien Massue, Karima Benelhadj, Siwar Chibani, Boris Le Guennic, Denis
Jacquemin, Pascal Retailleau, Gilles Ulrich, Raymond Ziessel
PII:
S0040-4039(14)00981-2
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.06.002
TETL 44726
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
8 April 2014
30 May 2014
3 June 2014
Please cite this article as: Massue, J., Benelhadj, K., Chibani, S., Guennic, B.L., Jacquemin, D., Retailleau, P., Ulrich,
G., Ziessel, R., Fluorescent 2-(2’-Hydroxybenzofuran) benzoxazole (HBBO) borate complexes: Synthesis, Optical
Properties and Theoretical Calculations, Tetrahedron Letters (2014), doi: http://dx.doi.org/10.1016/j.tetlet.
2014.06.002
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Fluorescent 2-(2’-Hydroxybenzofuran)
benzoxazole (HBBO) borate complexes:
Synthesis, Optical Properties and
Theoretical Calculations
Julien Massue,a∗ Karima Benelhadj,a Siwar Chibani,b Boris Le Guennic,d Denis Jacquemin,b,c* Pascal
Retailleau,e Gilles Ulrich,a∗ and Raymond Ziessela∗

1
Tetrahedron Letters
jou rn al h om ep a ge : www .e ls e v ie r .c om
Fluorescent 2-(2’-Hydroxybenzofuran) benzoxazole (HBBO) borate complexes:
Synthesis, Optical Properties and Theoretical Calculations
Julien Massue,a* Karima Benelhadj,a Siwar Chibani,b Boris Le Guennic,d Denis Jacquemin,b,c* Pascal
Retailleau,e Gilles Ulricha∗ and Raymond Ziessela∗
aLaboratoire de Chimie Moléculaire et Spectroscopie Avancées (LCOSA), ICPEES, UMR CNRS 7515, Ecole Européenne de Chimie, Polymères et Matériaux
(ECPM), 25 Rue Becquerel, 67087 Strasbourg Cedex 02, France, Tel : (+33) 368 85 26 97
b CEISAM UMR CNRS 6230, Université de Nantes, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France, Tel: (+33) 251 12 55 64.
c IUF, 103, Boulevard Saint-Michel, 75005 Paris Cedex 05, France.
d ISCR, CNRS-Université de Rennes 1, 1 Av. du General Leclerc, 35042 Rennes Cedex, France.
e Laboratoire de Cristallochimie, ICSN-CNRS, Bât 27, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, Cedex, France.
ARTICLE INFO
ABSTRACT
The multi-step synthesis, structural and optical properties of original luminescent borate
complexes derived from 2-(2’-hydroxybenzofuran)benzoxazole (HBBO) are reported.
Functionalization at position 3 of the benzofuran ring was readily achieved through an
electrophilic cyclization key step followed by a Sonogashira cross-coupling reaction. The optical
properties of the resulting boron difluoride dyes highlight different photophysical behaviors
depending on the nature of the substitution at position 3 of the benzofuran core (tBu-
Article history:
Received
Received in revised form
Accepted
Available online
phenylacetylene or NnBu2-phenylacetylene). The NnBu2-phenylacetylene moiety favors
a
Keywords:
sizeable intramolecular charge transfer as evidenced by a strong solvatochromism; a feature
further confirmed by ab initio calculations.
HBBO borate complexes
Heterocycles
Dyes
Fluorescence
TD-DFT Calculations
©2014 Elsevier Ltd. All rights reserved
.
———
* Corresponding authors: massue@unistra.fr, gulrich@unistra.fr,
ziessel@unistra.fr, Denis.Jacquemin@univ-nantes.fr

2
Tetrahedron
The elaboration of original luminescent emitters has become a (Schemes 1 and 2). The key intermediate benzofuran 6 was
major concern due to the large panel of applications targeted by synthesized in four steps as outlined in Scheme 1. Salicylaldehyde
light-emitting molecular devices. From organic optoelectronics1 to 3 can be obtained by selective monoiodination from commercially
biological labeling, sensing and medical imaging,2 dyes have available 4-methoxysalicylaldehyde using one equivalent of iodine
proven to be of paramount importance as light-interacting monochloride in acetic acid.10a Subsequent Sonogashira cross-
synthetic small molecules. The search for original, easily scalable, coupling reaction using 5% of [PdCl2(PPh3)2] as a catalyst with
modular fluorophores whose brightness surpasses that of 10% of CuI in toluene/triethylamine (3/1 v:v) in the presence of an
traditional luminophores has motivated the development of excess of 4-methoxyphenylacetylene13 leads to ethynyl-substituted
luminescent tetrahedral boron complexes in recent years. Among salicylaldehyde 4 in 88% yield. To avoid iodine-mediated
them, boron dipyrromethene dyes (BODIPY) have been, by far, oxidation of the phenol, 4 was protected with an acetate group
the leading family of boron(III) complexes and emerged as some using an excess of acetic anhydride in dichloromethane with a
of the most promising dyes due to outstanding chemical and catalytic amount of pyridine. Acetate protected salicylaldehyde 5
optical properties, e.g. sharp and narrow absorption and was isolated in 94% yield. Substituted benzofuran 6 was obtained
fluorescence profiles, high absorption coefficients, high quantum following an electrophilic cyclization reaction using molecular
yields, good solubility and strong chemical and photochemical iodine as first developed by Larock et al.14 Heterocycle 6 was
stability.3 The main drawback of BODIPY dyes lies in the fact that obtained in 74% yield as yellow single crystals suitable for X-Ray
they are weakly luminescent in the solid-state due to strong diffraction analysis (vide infra).
intermolecular interactions in the molecular packing.
Circumvention of aggregation-caused quenching can be achieved
by functionalizing the BODIPY core with bulky substitutents
leading to enhanced solid-state luminescence.4 More recently,
coordination of a π-conjugated chelate to a boron(III) fragment, as
BF2 or BAr2 led to the development of alternative B(III)
luminescent complexes which have been engineered from
saturated bidentate N^N5 and N^O6 chelates.7 Among the latter, 2-
(2’-hydroxyphenyl) benzoxazole (HBO) have proven to be
efficient chelates for BF28 or BPh29 fragments giving stable borate
complexes with tunable optical properties. These dyes display an
intense fluorescence emission spanning from the UV to the visible,
both in solution and in the solid state. Moreover, extension of the
conjugation of the HBO core with ethynyl fragments leads to
different photophysical profiles depending on the nature of the
electronic substitution and its position on the phenolic ring.10
Enlargement of the π-conjugated system is indeed a common
synthetic strategy to red-shift the optical properties of a given dye
while rigidification of molecular structures often leads to
improved quantum yields.11
Scheme 1. Synthesis of substituted benzofuran 6.
The intermediate HBBO 7 and 8 were formed by condensation
of 6 with 2-hydroxyaniline or 5-tBu-2-hydroxylaniline respectively
in refluxing ethanol followed by oxidation of the intermediate
carbinolamine with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
(DDQ) (Scheme 2). Compounds 7 and 8 display a characteristic
proton NMR signal (around 12 ppm) for the H-bonded phenolic
proton. Moreover, their formation can be readily monitored by the
appearance of a strong fluorescence in the solid-state due to an
Excited-State Intramolecular Proton Transfer (ESIPT).15 Insertion
We wish herein to further investigate the influence of
conjugation extension and rigidification on the optical properties
of HBO borate dyes. We have thus chosen to structurally modify
the HBO core by introducing a rigid benzofuran skeleton. This
heterocycle seems to be a tool of choice to enhance the
photophysical properties of the resulting boron(III) complexes
because it is a flat, rigid scaffold whose synthetic access is well-
described due to its ubiquity in numerous structures ranging from
natural products to medicinal drugs.12
t
of a Bu-phenyl or NnBu2-phenyl ethynyl fragment was possible
through Sonogashira cross-coupling reactions using 5% of
[PdCl2(PPh3)2] as a catalyst with 10% of CuI in the presence of an
excess of the corresponding substituted phenylacetylene. Note that
t
an additional Bu group was inserted in 10 as R1 for solubility
issues. Pure HBBO dyes 9 and 10 were isolated in 71 and 43%
respectively as yellow powders. Boron complexation was achieved
using BF3.Et2O in the presence of a base (DIEA) affording pure
HBBO borate complex 1 and 2 in 74 and 79% yields respectively.
In this article, we describe the synthesis, structural and optical
properties along with Time-Dependent Density Functional Theory
The purity of all new compounds was assessed by H, 13C NMR
1
along with mass spectrometry and elemental analysis.
(TD-DFT)
calculations
of
novel
rigidified
2-(2’-
hydroxybenzofuran)benzoxazole (HBBO) borate complexes based
on a decorated benzofuran scaffold (Figure 1).
As already observed on related examples,8a,10 boron
complexation to the N^O chelate leads to the disappearance of the
downfield distinctive phenolic proton in H NMR along with a
1
splitting of the aromatic protons. The two para-substituted phenyl
rings exhibit two AA’BB’ systems at δ = 8.21/6.95 ppm (J = 8.5
Hz) and at δ = 7.50/6.66 (J = 8.8 Hz). The methoxy and
dibutylamino protons are in good accordance with the signals
expected such functional groups in terms of chemical shifts and
integration. Finally, the 13C NMR provides definitive proof of the
complex 2 structure by displaying accounted signals for all tertiary
and quaternary carbons. In particular, the sp carbons of the
acetylenic spacer are observed at 97.6 and 99.0 ppm. The five
signals in the upfield region match with expected signals for the
Figure 1. 2-(2’-Hydroxybenzofuran)benzoxazole (HBBO) Borate
complexes 1 and 2.
HBBO borate complexes 1 and 2 substituted with an ethynyl
substituent at position 3 of the benzofuran ring were prepared
following a synthetic route which can be divided into two schemes

3
methylene carbons present in the butyl chains and the methoxy
group.
Single crystals of compound 6 suitable for X-Ray diffraction
were obtained by slow evaporation of
a
concentrated
dichloromethane solution. The ORTEP diagram of 6 and the
overlay of the two conformers observed are represented on Figure
2. Compound 6 crystallizes in the centrosymmetric triclinic space
group with two molecules in the asymmetric unit. If both
conformers are basically planar except for the acetate substituent,
which is orthogonal to the rest of the molecule, they differ by
having the methoxy and acetate groups pointing to opposite
directions (Figure 2).
Scheme 2. Synthesis of HHBO borate complexes 1 and 2
Figure 2. (Left) ORTEP view for 6 showing the atom-labelling scheme for one conformer. Thermal ellipsoids are plotted at the 50% level. (Right) Overlay of
the two conformers present in the asymmetric unit of the single crystal of 6.
Figure 3. (a) Partial view detailing the stacking interactions for compound 6. (b) Partial view perpendicular to the layer plane.
Moreover, the anisole ring is less coplanar with the
benzofuran group in the first conformer than in the other one.
As for the crystal packing, the molecules are lying within the (1
2 4) plane with interplanar distance of 3.56 Å. Within each
layer, molecules are associated through reciprocal interactions
C – H····C between carbon sp2 and methyl group of the
inversion-related isomer and I····O from the aldehyde group
between pseudo-inversion related molecules.
The photophysical properties of HBBO borate complexes 1
and have been studied in various solvents and are
2
summarized in Table 1 and the experimental curves shown in
Figure 4 for 1 and Figure 5 for 2. The two complexes exhibit
similar absorption profiles that is a low-energy band with a
maximum at 360-397 nm and a higher-energy band around 300
nm typical of π-π* transitions. Absorption coefficients range
from 14600 to 35700 M-1.cm-1 for the low-energy band.
Excitation at 350-385 nm leads to an emission band in the

4
Tetrahedron
visible region at 470 and 491 nm with quantum yields
366 35800
501
565
7400 0.23 3.9
10000 0.08 2.2
CH2Cl2 + HClg
CHCl3
reaching 27 and 41% in toluene and CH2Cl2 respectively for
complex 1. As expected, the emission of 1 is only slightly
affected by the dipolar moment of the solvent. The nanosecond
lifetimes determined are consistent with a singlet emitting state.
360 27100
Interestingly, for complex 2, a different photophysical
profile is observed. The presence of a strong electron-donating
4-NnBu2-phenylacetylene module leads to a sizeable red-
shifted emission as compared to complex 1. For example, in
CH2Cl2, complex 2 displays an intense emission band centered
at 542 nm (Φ = 12%) as compared to 491 nm (Φ = 41%) for
complex 1. The emission profile of complex 2 is also strongly
dependent on the dipolar moment of the solvent. Indeed, in all
solvents, complex 2 exhibits a broad emission band whose
maximum stretches from 504 to 565 nm with moderate
quantum yields (32 to 8%) suggesting a strong intramolecular
internal charge transfer (ICT) responsible for the emissive
excited state.
Table 1. Optical data for HBBO dyes 1 and 2 in various
solvents at room temperature.
λabs
(nm)
∆
a
ε (M-1.cm-1) λem (nm)
Φ f
τ (ns) Solvent
SS
(cm-1)
392 23800
390 25500
397 16300
395 17100
368 16300
365 27500
363 35700
362 36100
468
471
470
491
504
532
546
542
4200 0.52 3.4
4600 0.58 4.5
3900 0.27 2.5
4900 0.41 5.6
7300 0.32 5.7
8700 0.18 1.2
9200 0.11 1.0
9600 0.12 1.6
toluene
CH2Cl2
toluene
CH2Cl2
cyclohexane
toluene
THF
1
2
3
CH2Cl2
Figure 4. Absorption (blue), excitation (dashed blue) and emission (green) of complex 1 in (a) toluene and (b) dichloromethane at rt.
Figure 5. (left) Absorption (dashed) and emission (plain) of complex 2 in cyclohexane (navy blue), toluene (blue), CH2Cl2 (green), CH2Cl2 + HClg (light
green) THF (red) and CHCl3 (purple) and (right) (a) irradiated CH2Cl2 solution of complex 1 and (b) irradiated solutions of complex 2 in various solvents (from
left to right: cyclohexane, toluene, THF, CH2Cl2, CH2Cl2 + HClg, CHCl3) with a bench UV lamp (λexc = 365nm).

5
To validate this hypothesis, absorption and emission were
recorded after bubbling HCl gas into a solution of 2. Since the
ICT character is reduced due to the protonation of the lone
electron pair of the nitrogen in the 4-NnBu2-phenylacetylene
fragment, the emission undergoes a significant blue-shift along
with an increase of the quantum yield (λem = 542 mn, Φ = 12%
for 2 in CH2Cl2 compared to λem = 501 mn, Φ = 23% for 2 in
CH2Cl2 + HClg), similar feature is observed in CHCl3 as a
shoulder due to HCl trace in this solvent.
Conclusions
In short, a new family of fluorescent borate dyes (HBBO)
incorporating benzofuran heterocycle, which actively
a
participates in the extension of the π-conjugation, has been
synthesized. They display a significant red-shift in their
maximum emission wavelength as compared to related HBO
borate dyes. The presence of a strong donor residue in the 3
position promotes an ICT as confirmed by spectroscopic
studies and TD-DFT calculations allowing to shift the emission
up to 565 nm. This stretch paves the way for the engineering of
similar dyes emitting in the near-IR.
To gain more insights into the nature of the excited-states,
TD-DFT calculations were performed, following a recently
proposed approach adequate for HBO structures.16 Bulk
solvation effects are accounted at all steps; not only the vertical
absorption energies are determined on the ground-state optimal
structures, but the geometry of the first excited-state is also
fully optimized, allowing a simulation of the Stokes’ shift. All
calculations use a range-separated hybrid accounting for
dispersion effects, as this allows a consistent treatment of both
charge-transfer excitations and weak interactions (see the SI for
details). In CH2Cl2, the computed Stokes’ shifts are 6598 and
9856 cm-1 for 1 and 2 which are larger than the measured
values especially for complex 1 (Table 1) but are in qualitative
agreement with experiment, that is the Stokes’ shift is larger for
2 than for 1. Ground and excited-state Cartesian coordinates for
all systems are available in the SI. The most notable changes
between the two geometries is relative orientations of the main
core of the molecule and the p-OMe-Ph donor. For 1 (2), it
goes from 10.3° (5.6°) in the ground-state to 0.4° (0.1°) in the
excited-state, hinting an increased delocalization in the excited-
state, as expected. The density difference plots corresponding
to the optical transition for these dyes can be found in Figure 6.
In 1, an ICT is observed from the benzofuran fragment towards
the benzoxazole moiety; the ethynylphenyl fragment does not
significantly participate in the excited-state that acts as an
electron donor (mostly in blue in Figure 6).
Acknowledgments
The authors thank CNRS and Rhin-Solar supported by the
European Fund for Regional Development (FEDER) in the
framework of the Programme INTERREG IV Upper Rhine,
Project nr C25 for providing financial support. S.C. and D.J.
acknowledge the European Research Council (ERC) for financial
support in the framework of Starting Grant (Marches - 278845).
This research used resources of the GENCI-CINES/IDRIS, of the
CCIPL (Centre de Calcul Intensif des Pays de Loire) and of a local
Troy cluster.
Supplementary Data
Supplementary data associated with this article can be found
online.
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