Straightforward Synthesis, Electrochemical Properties, and Gel Formation of Thiacalix[n]thiophenes

Article abstract of DOI:10.1002/asia.201501347

A facile synthetic approach toward thiacalix[n]thiophene homologues (n=4-6) is presented herein. Pd-catalyzed coupling of 2,5-dibromothiophene derivatives with stannyl sulfide gave various thiacalix[n]thiophenes in good yields. The optical and electrochem

Full text of DOI:10.1002/asia.201501347

DOI: 10.1002/asia.201501347
Communication
Macrocycles
Straightforward Synthesis, Electrochemical Properties, and Gel
Formation of Thiacalix[n]thiophenes
Masashi Hasegawa,* Yoshiki Honda, Ryota Inoue, and Yasuhiro Mazaki[a]
alyzed coupling between a 2,5-dibromodithienothiophene (di-
Abstract: A facile synthetic approach toward thiacalix[n]-
thiophene homologues (n=4–6) is presented herein. Pd-
bromo-DTT) derivative and (nBu3Sn)2S as the sulfur source.[6]
Typically, this type of coupling reaction is employed for the
catalyzed coupling of 2,5-dibromothiophene derivatives
preparation of symmetrical thioethers.[7] However, in our case,
with stannyl sulfide gave various thiacalix[n]thiophenes in
the coupling reaction resulted in cyclic homologues of 4–9-
good yields. The optical and electrochemical properties of
mers in high yields, together with only small amounts of acy-
the produced cavitands were investigated. Furthermore,
clic products. This result strongly encouraged us to employ the
gelation was observed in some solvents.
developed method for the synthesis of a series of thiacalix[n]-
thiophenes that are inaccessible by conventional cyclization
methods. Here, we report an efficient approach toward a series
Thiacalix[n]thiophenes are cyclic oligomers comprising sulfur-
bridged thiophenes; they are analogues of thiacalix[n]arenes,
which are employed as host molecules in supramolecular
chemistry (Figure 1).[1–3] The presence of thiophene moieties
of novel thiacalix[n]thiophenes with various substituents
(Scheme 1). The electronic structure and redox properties of
the produced compounds are also presented. Moreover, we
found that some thiacalix[n]thiophenes exhibited gelation in
Figure 1. Structures of thiacalix[n]thiophenes (1a–c).
endows these cavitands with potentially interesting properties
derived from their electron-donating ability. While a rich set of
examples of thiacalix[n]arenes have been reported, thiacalix[n]-
thiophenes have not been extensively explored thus far due to
synthetic difficulties. In 1997, two groups independently re-
ported the synthesis of 1a via a difficult approach based on
a multistep structural elongation or a simple approach from
a thiophene framework in extremely low yield.[4,5] Therefore,
details such as the electrochemical and supramolecular proper-
ties of thiacalix[n]thiophenes are still unknown. To develop
thiacalix[n]thiophenes for intriguing applications, it is necessary
to improve their accessibility and structural diversity.
Scheme 1. Synthesis of thiacalix[n]thiophenes 1–7 and 8.
certain solvents.
The results of the cyclization reactions are listed in Table 1.
Treatment
of
2,5-dibromo-3,4-disubstituted-thiophenes
(0.5 mmol) with (nBu3Sn)2S (0.5 mmol) in the presence of
[Pd(PPh3)4] (0.06 mmol, 12 mol%) in DMF at 110 8C provided
the corresponding thiacalix[n]thiophenes (n=4–6). Initially, we
employed 2,5-dibromothiophene as a pristine thiophene re-
source for the reaction (entry 1). However, only acyclic oligo-
thiophenes linked with sulfur atoms were obtained. On the
other hand, a small amount of 4-mer 2a and 5-mer 2b togeth-
er with acyclic molecules as the main products were formed
when 2,5-dibromo-3,4-dimethylthiophene was employed
(entry 2). Although the coupling reaction proceeded smoothly,
the cyclization to thiacalix[n]thiophene was disfavored under
the reaction conditions. Improved yields were observed when
Recently, we established a simple protocol for the synthesis
of sulfur-bridged dithienothiophene macrocycles using Pd-cat-
[a] Dr. M. Hasegawa, Y. Honda, Dr. R. Inoue, Prof. Dr. Y. Mazaki
Department of Chemistry, School of Science
Kitasato University
Sagamihara, Kanagawa 252-0373 (Japan)
Fax: (+81)426-778-8158
E-mail: masasi.h@kitasato-u.ac.jp
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/asia.201501347.
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Table 1. Palladium-catalyzed cyclization of 2,5-dibromothiophene deriva-
tives.[a]
Entry
R
Yield [%][b]
n=4
n=5
n=6
1
H
–
–
–
2
CH3
nBu
tBu
2a, 7
3a, 27
4a, trace
2b, 3
3b, 11
–
–
3[c]
4
3c, 5
–
5
6
7
5a, 8
5b, trace
6b, 6
–
6a, 27
7a, 26
6c, 5
7c, 2
7b, 8
[a] Reaction conditions: [thiophene]/[S(nBu3Sn)2]/[Pd(PPh3)4]=0.5:0.5:0.06
(mmol for entries 1, 3–7), 0.5:0.5:0.09 (mmol for entry 2), in 25 mL DMF at
110 8C under Ar. [b] Isolated yield. [c] Trace amount of 7-mer 3d was ob-
tained.
Figure 2. DFT-optimized structures (alternate conformations) of (a) 2a,
(b) 5a, (c) 2b, and (d) 2c in ball-and-stick views. The methyl and p-tolyl
group substituents are represented in a wire-frame view for clarity.
nBu was employed as the substituent (entry 3). Cyclic 4-mer
(3a), 5-mer (3b), 6-mer (3c), and 7-mer (3d) were obtained
after GPC separation. In contrast, in the reaction with tBu, only
a trace amount of 4a was observed in the mass spectrum, to-
gether with the recovered starting dibromothiophene and its
dehalogenated counterparts (entry 4). These results imply that
the bulkiness of the substituents in the 3,4-position affects the
cyclization.
2b as an energy minimum structure (Figure 2c). The diagonal
distance S···S in the pentagonal shape is calculated to be
about 9.5 Š. As for the calculation of 2c, a higher symmetrical
structure having a larger cavity (ca. 11.8 Š of the diagonal dis-
tance) was obtained as a minimum (Figure 2d).
These results encouraged us to explore other thiacalix[n]-
thiophenes with moderately bulky substituents. Indeed, 3,4-
bis(4-alkylphenyl)thiophenes readily underwent cyclization
(Table 1; entries 5–7). When the reaction was performed with
2,5-dibromo-4,5-bis(p-tolyl)thiophene as the starting com-
pound, 5a was obtained in 8% yield together with a trace
amount of 5b. However, compound 5a was not very soluble
in common organic solvents. Higher yields of the cyclic 4-mer
were obtained in the reactions carried out with 4-(n-butyl)-
phenyl (entry 6) and 4-tert-butylphenyl (entry 7) substituents.
In these cases, larger cyclic oligomers were also obtained, to-
gether with small amounts of the acyclic products. Thus, the
solubility of the product would be critical to the reaction yield.
Although we did not obtain a single crystal suitable for X-
ray analysis, we carried out DFT calculations of the model com-
pound 2a–c and 5a to obtain structural information of the
macrocyclic compounds. Thus, DFT calculations of 2a, per-
formed at the B3LYP/6-31G(d,p) level of theory, revealed that
the 1,3-alternate geometry with S4 symmetry was the most
stable conformer (Figure 2a), with a considerably energy differ-
ence from the others.[8] The 1,3-alternate conformer of 2a pos-
sesses a square cavity with a diagonal distance of ca. 8.4 Š.
The four sulfur atoms at the corners are almost coplanar. In
sharp contrast, the optimized 1,3-alternate geometry of 5a ex-
hibits a puckered quadrilateral conformation, while its diagonal
distance is similar to that of 2a (Figure 2b). This distortion of
the four sulfur atoms arises from the steric repulsion of the p-
tolyl groups on the adjacent thiophene rings. On the contrary,
DFT calculation suggests a folding pentagonal conformation in
To investigate the electronic structure of the produced com-
pounds, their absorption spectra were measured in CH2Cl2.
Similar spectra were observed for 3a–c in CH2Cl2 (Figure S19,
Supporting Information). The longest absorption maxima were
in the range of 290–300 nm, suggesting little extension of the
p-conjugation through the S atoms at the corners of the com-
pounds.
The electrochemical properties of homologues 3a–c, togeth-
er with 3,4-dibutyl-2,5-bis(phenylthio)thiophene 8 (Scheme 1),
were investigated using cyclic voltammetry (CV) and differen-
tial pulse voltammetry (DPV) in 1,2-dichloroethane (Figure 3);
the results are summarized in Table 2. Compound 3a showed
two well-dissolved reversible redox waves in CV, while com-
pound 8 showed two irreversible redox waves. In DPV meas-
urements, compound 3a exhibited redox peaks at 0.50 and
0.78 (vs. Fc/Fc+), while compound 8 showed redox peaks at
0.62 and 1.13 V. Considering the number of observed redox
waves in 8, the redox process of these systems is associated
with the sulfide linkage atoms. This result is consistent with
the redox processes of the DTT ring system found in a previous
study.[6] In addition, the E1 value of 3a was much lower than
that of 8. The lowering of the first redox of 3a relative to 8
suggests the formation of 3a +, and its charge/electron can be
C
delocalized over the sulfide linkers.[9] In fact, electronic spectra
+
C
in oxidation state of 3a by applying the constant voltage
beyond the E1 value gave a very broad absorption band in the
NIR region (lmax: 1240 nm) owing to the charge resonance
among the thiophene moieties (Figure S20).
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Figure 3. (a) Cyclic and (b) differential pulse voltammograms of 3a
(0.63 mm), 3b (0.38 mm), and 3c (0.34 mm) in 1,2-dichloroethane.
Figure 4. (a) Photograph of the gel of 7a (toluene), (b, c) SEM images ob-
tained from the air-dried gel, and (d) UV/Vis spectra of 7a in the gel state
from toluene (air-dried gel on a quartz plate), in CH2Cl2 (7.9”10À5 m), and in
toluene at lower concentration (6.6”10À5 m).
Table 2. Redox potentials of 3a–c and 8.[a]
ox
ox
ox
Compd.
E1 [V]
E2 [V]
E3 [V]
EHOMO
[eV][b]
Calc. EHOMO
[eV][c]
6a formed no gel precipitates due to high solubility in various
solvents.
3a
3b
3c
8
0.50
0.57
0.53
0.62
0.78
0.80
0.85
1.13
–
À5.28
À5.37
À5.33
À5.42
À5.46
À5.92
À6.22
–
To investigate the driving force for the gelation behavior,
UV/Vis absorption and VT-NMR spectroscopic data of 7a were
measured. The absorption of the gel was slightly red-shifted
compared with the solution spectra, implying intermolecular
interactions in the p-frameworks of thiacalix[4]thiophene. Al-
though compound 7a did not exhibit a remarkable concentra-
0.97
1.02
–
[a] All potentials were obtained from DPV measurements in 1,2-dichloro-
ethane containing 0.1m nBu4NPF6 at 258C with a Pt working electrode.
Potentials were measured against Ag/AgCl/KCl in a Luggin capillary and
were converted to the values vs. Fc/Fc+. [b] Estimated from EHOMO
=
1
tion-dependence in the H NMR spectra at room temperature,
À(4.80+E1 (vs. Fc/Fc+)). [c] Using HOMO energy levels of 2a–c in DFT
1/2
a temperature dependence of the chemical shift was observed
in [D8]toluene solution (Figure 5). When the temperature was
decreased from 858C to À108C, the signals assigned to the ar-
omatic proton Ha on the benzene ring and the methyl proton
of tBu group shifted upfield from d=7.14 and 1.15 ppm to
7.07 and 1.07 ppm, respectively, while the signals assigned to
Hb shifted downfield from d=7.09 to 7.21. Finally, a broadening
of the signals was observed after turning off the spinning in
the NMR spectrometer due to the formation of a gel in the
tube. The spectrum of the gel is quite similar to that of the so-
lution at lower temperature. Thus, the observed upfield shifts
of Ha and tBu protons might be attributed to the shielding
effect of neighboring aromatic rings derived from the molecu-
lar association in [D8]toluene solution. In sharp contrast, the
signals of all protons slightly shifted downfield in a uniform
way upon cooling in CDCl3, and no gelation occurred under
the conditions.
calculations.
As for 3b, three redox waves were found, and their poten-
tials were at 0.57, 0.80, and 0.97 V. The E1 value of 3b was
slightly higher than that of 3a, presumably due to the less
conjugated structure of 3b arising from the folded molecular
structure revealed in DFT calculations (Figure 2c). Finally, com-
pound 3c exhibited a complex redox behavior. Three redox
peaks at 0.53, 0.85, and 1.02 V were observed owing to the se-
quential redox process. From the comparison of the first redox
potentials, the HOMO levels of these homologues are in the
order of 3a>3c>3b, although the calculated HOMO levels of
the model compounds are 2a>2b>2c. These inconsistencies
are presumably attributed to the conformational fluctuation in
the larger cyclic oligomers in solution.
Interestingly, compound 7a formed an opaque gel in tolu-
ene and PhCl (CGC: critical gel concentration=6.6 wt% and
4.4 wt%, respectively) after a heating–cooling procedure (Fig-
ure 4a). SEM observation of the resulting xerogel air-dried on
a Si-wafer revealed that the gel had retiform structures com-
posed of entangled nanoscale fibrous rods. In other solvents,
a precipitate or rod-shaped small crystals were formed. Al-
though compound 5a exhibited very poor solubility in a wide
variety of solvents, a jelly-like precipitate was formed in CHCl3
at low concentrations. Furthermore, compounds 2a, 3a, and
In general, calix[n]arenes bearing hydrogen-bonding (H-
bonding) units often form supramolecular gels through self-as-
sembly.[10,11] These gel materials lead to cavity-assembled
porous solids (CAPs), which can provide excellent molecular
recognition abilities. However, in the present system, there is
no H-bonding site to facilitate supramolecular assemblies. In
addition, only thiacalix[n]thiophene having tert-butylphenyl
groups exhibits the gelation properties. Thus, a subtle balance
between the p-framework and alkyl groups on the thiophene
as well as the solubility is an important factor for the gelation.
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tigation is currently in progress on functionalized CAPs based
on these appealing frameworks.
Acknowledgements
This research was supported by the Ministry of Education, Cul-
ture, Sports, Science, and Technology of Japan through
a Grant-in-Aid for Scientific Research (grant number 20438120).
We thank Prof. Dr. Masahiko Iyoda (Tokyometropolitan Univer-
sity) and Prof. Dr. Takahiro Tsuchiya (Kitasato University) for
helpful discussions. All calculations were performed at the Re-
search Centre for Computational Science, Okazaki, Japan.
Keywords: coupling reaction · gels · macrocycles · organic
gelators · thiacalix[n]thiophene
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Recently, the gelation behavior of p-conjugated molecules
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phenes (n=4, 5, 6). Despite the lack of H-bonding units, thia-
calix[4]thiophenes with phenyl groups formed gels through
molecular association. To the best of our knowledge, there
have not been any previous examples of organic gelators
based on calix[4]arene without H-bonding units. Further inves-
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Manuscript received: December 4, 2015
Revised: December 28, 2015
Accepted Article published: January 13, 2016
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