A new synthetic route to 5,6,11,12-tetraarylethynyltetracenes

Article abstract of DOI:10.1039/c8ob02450b

A new synthetic route to 5,6,11,12-tetrakis(arylethynyl)tetracenes, π-extended rubrenes, was developed via [4 + 2] cycloadditions of dialkynylisobenzofuran and 1,4-naphthoquinone. Introduction of arylethynyl groups by double nucleophilic additions to tetracenequinone gave sterically congested (arylethynyl)tetracenes after reductive aromatization. The photophysical properties of the newly prepared π-conjugated molecules are also evaluated.

Full text of DOI:10.1039/c8ob02450b

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A new synthetic route to
5,6,11,12-tetraarylethynyltetracenes†
Cite this: Org. Biomol. Chem., 2018,
16, 9143
Kei Kitamura,a Kenta Asahina,a Yusaku Nagai,a Keshu Zhang,a Shogo Nomura,b
Received 1st October 2018,
Accepted 8th November 2018
a
Katsunori Tanaka b,c and Toshiyuki Hamura
*
DOI: 10.1039/c8ob02450b
rsc.li/obc
A new synthetic route to 5,6,11,12-tetrakis(arylethynyl)tetracenes, compound 1 (step 4). Along these lines, we now report an
π-extended rubrenes, was developed via [4 + 2] cycloadditions of efficient synthetic access to π-extended rubrenes possessing
dialkynylisobenzofuran and 1,4-naphthoquinone. Introduction of various arylethynyl groups at the peri-positions. Moreover,
arylethynyl groups by double nucleophilic additions to tetracene- photophysical properties of the newly prepared poly-ethyny-
quinone gave sterically congested (arylethynyl)tetracenes after lated tetracenes are evaluated. Also described is the application
reductive aromatization. The photophysical properties of the of the parent compound 1a to a cellular imaging agent.
newly prepared π-conjugated molecules are also evaluated.
Scheme 3 shows the [4 + 2] cycloaddition of dialkynyliso-
benzofuran. Upon mixing of isobenzofuran 3a and naphtho-
quinone 5 (CH2Cl2, r.t.), a new spot corresponding to the cyclo-
adduct 6a was observed by TLC. Further reaction at the same
temperature, however, did not completely consume the start-
We previously reported a preparation of 5,6,11,12-tetraarylethy-
nyltetracene 1, a new class of π-extended rubrenes, via [4 + 2]
cycloaddition of dialkynylnaphthalyne 2 and dialkynylisoben-
zofuran 3 (Scheme 1).1,2 In this reaction, two alkynyl groups on
the naphthalyne 2 can lower the LUMO energy, allowing the
practical construction of the sterically overcrowded structure
through their efficient HOMO–LUMO interaction.
This approach, however, has a problem in that the yield of
the aromatization (4 → 1) is low or moderate owing to the unex-
pected reactivities derived from the closely located peri-ethynyl
groups in epoxytetracene 4 under the acidic conditions.3
To solve this problem, we focused on developing a new syn-
thetic route to π-extended rubrene 1 using dialkynylisobenzo-
furan 3 as a reactive platform.4,5 Our second approach consists
of four-step syntheses, which is depicted in Scheme 2.6 In the
first step, the [4 + 2] cycloaddition of dialkynylisobenzofuran 3
and 1,4-naphthoquinone (5) gives the cycloadduct 6, which is
converted to the tetracenequinone 7 by aromatization (step 2).
Subsequent introduction of two alkynyl groups by double
nucleophilic additions of alkynyl anions (step 3), and reductive
aromatization of the resulting diol 8 would produce the target
Scheme 1 The first syntheses of π-extended rubrenes 1 via [4 + 2]
cycloaddition of naphthalyne and isobenzofuran.
aDepartment of Applied Chemistry for Environment, School of Science and
Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan.
E-mail: thamura@kwansei.ac.jp
bBiofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering
Research, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan
cBiofunctional Chemistry Laboratory, Kazan Federal University,
18 Kremlyovskaya street, Kazan 420008, Russia
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c8ob02450b
Scheme 2 New synthetic route to π-extended rubrenes 1.
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Scheme 4 Aromatization of cycloadduct 6a to tetracenequinone 7a.
Scheme 3 [4 + 2] cycloaddition between isobenzofuran 3a and 1,4-
naphthoquinone (5).
Further transformation of the tetracenequinone 7a to
π-extended rubrene 1a was achieved through double nucleo-
philic additions of phenylethynyllithium, followed by SnII-
mediated reductive aromatization (Scheme 5). Importantly, the
nucleophilic addition of alkynyllithium to 7a occurred cleanly
by warming the reaction mixture to room temperature, in spite
of the high steric hindrance between incoming nucleophile
and proximal alkynyl groups.
In a similar manner, the substituted derivatives 1b and 1c,
having four p-tolylethynyl or (4-bromophenyl)ethynyl groups at
both peri-positions, were efficiently synthesized by this four-
step sequence including the tetracenequinones 7b and 7c as
key intermediates (Scheme 6).
Fig. 1 [4
+ 2] cycloaddition between isobenzofuran 3a and 1,4-
It should be noted that the developed method has high syn-
thetic potential in that the sterically congested derivative 1d
naphthoquinone (5) monitored by NMR. (a) A: 5 min, B: 2 h, C: 7 h, D:
15 h.
ing materials 3a and 5, indicating their equilibrium with the
cycloadduct 6a. Indeed, 1H NMR analysis revealed that the
cycloadduct 6a including endo- and exo-isomers was readily
formed after dissolving the isobenzofuran 3a and naphthoqui-
none 5 in CDCl3 at room temperature (see A in Fig. 1). After
7 h, the ratio of 3a, 5, exo-6a, and endo-6a almost became con-
stant (see D in Fig. 1). The stereochemistry of the exo-6a and
endo-6a was tentatively assigned by consideration of the chemi-
cal shift of each methine proton.7
Scheme 5 Transformation of tetracenequinone 7a to π-extended
rubrene 1a.
After further study of this [4 + 2] cycloaddition, we were
pleased to find that the solvent choice is crucial to produce the
high yield of the cycloadduct 6a: when the above-mentioned
reaction was performed in toluene at 90 °C, the [4 + 2] cyclo-
adduct 6a gradually precipitated from the solution due to its
low solubility in toluene, affording the essentially pure
product 6a almost in quantitative yield (Scheme 3).
Interestingly, the endo isomer 6a was solely produced under
these conditions. By dissolving in CDCl3 (25 °C, 26 h), the
cycloadduct 6a again underwent cycloreversion to give the dia-
lkynylisobenzofuran 3a and 1,4-naphthoquinone (5).8
Scheme 4 shows the conversion of the [4 + 2] cycloadduct
6a to tetracenequinone 7a. Upon heating of cycloadduct 6a in
the presence of TsOH at 60 °C, the cycloreversion occurred
quickly, and the aromatized product 7a was not obtained at
all.9,10 On the other hand, treatment of the cycloadduct 6a
with LiI and DBU at low temperature (CH2Cl2, 0 °C)11 under-
went the clean aromatization without invoking the cyclorever-
sion to give the tetracenequinone 7a in 95% yield.
Scheme 6 Preparation of π-extended rubrenes 1b–1d.
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possessing four 2,6-xylylethynyl groups on the tetracene core
was easily accessible in good yield. This is a sharp contrast
from our previous method by acid-promoted aromatization of
the epoxy tetracene 4d (Ar: 2,6-xylyl), where the product 1d was
obtained in poor yield, and a sizable amount of furan (struc-
ture not shown) was produced.1
To evaluate the photophysical properties, UV–Vis spectra of
π-extended rubrenes 1a–1d were measured in chloroform
(Fig. 2). The π-extended rubrene 1a has its absorption
maximum at 640 nm, which was greatly red-shifted over
100 nm from that of the parent rubrene, indicating effective
π-extension by the existence of four phenylethynyl groups on
the tetracene core. The π-extended rubrenes 1b and 1c with
para-substitution denoted the similar tendency of 1a, whereas
the absorption maximum of the sterically congested derivative
1d was slightly blue-shifted (623 nm).
Fluorescence spectra were also measured in chloroform
(Fig. 3). The π-extended rubrenes 1a–1d showed a fluorescent
maximum peaking at around 690 nm, which were excited at
their absorption maximum. A larger Stokes shift was observed
in 1d (1620 cm−1) compared to that of 1a (1200 cm−1). The
absolute fluorescent quantum yields of these π-extended
derivatives were nearly 10%, which were lower than that of the
parent rubrene.
Fig. 4 Fluorescence imaging of HeLaS3 cells by π-extended rubrene.
The cells were treated with 100 µM of 1a for 30 min at 37 °C and ana-
lyzed by fluorescence microscopy. Green channel: λem = 620 nm, λex
=
700 nm. Scale bar: 20 µm.
Finally, preliminary investigation of cellular imaging using
π-extended rubrene was performed by treating the HeLa cells
with 1a for 30 min at 37 °C. Fluorescence signals from cells
upon excitation at 620 nm indicate a future applicability of
π-extended rubrene as a bioimaging probe (Fig. 4).
Conclusions
In conclusion, [4 + 2] cycloaddition of dialkynylisobenzofuran
and 1,4-naphthoquinone allowed rapid construction of alkyny-
lated tetracenequinones, which were amenable to transform-
ation en route to tetrakis(arylethynyl)tetracenes. Further
studies on the application of these attractive π-conjugated
molecules to organic electronics materials and fluorescent
probes are underway in our laboratories.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This work was supported by JSPS KAKENHI Grant Number
JP15H05840 in Middle Molecular Strategy and JST ACT-C Grant
Number JPMJCR12YY, Japan.
Fig. 2 UV–Vis absorption spectra of π-extended rubrenes 1a–1d.
Notes and references
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Fig. 3 Fluorescence spectra of π-extended rubrenes 1a–1d.
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