Synthesis of bis-fused tetrathiafulvalene with mono- and dicarboxylic acids

Article abstract of DOI:10.1016/j.tetlet.2012.04.064

Bis-fused tetrathiafulvalenes with mono- and dicarboxylic acids, 2-{5-(1,3-dithiol-2-ylidene)-[1,3]dithiolo[4,5-d][1,3]dithiol-2-ylidene}-1, 3-dithiole-4-carboxylic acid (1) and 2-{5-(1,3-dithiol-2-ylidene)-[1,3] dithiolo[4,5-d][1,3]dithiol-2-ylidene}-1,3

Full text of DOI:10.1016/j.tetlet.2012.04.064

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Tetrahedron Letters 53 (2012) 3277–3280
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of bis-fused tetrathiafulvalene with mono- and dicarboxylic acids
Takeshi Terauchi a, Yuka Kobayashi a, , Yohji Misaki b
⇑
a National Institute for Materials Science (NIMS), Sengen 1-2-1, Tsukuba, Ibaraki 305-0047, Japan
b Department of Applied Chemistry, Graduate School of Engineering, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime 790-8577, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 February 2012
Revised 9 April 2012
Accepted 13 April 2012
Available online 25 April 2012
Bis-fused tetrathiafulvalenes with mono- and dicarboxylic acids, 2-{5-(1,3-dithiol-2-ylidene)-[1,3]dithi-
olo[4,5-d][1,3]dithiol-2-ylidene}-1,3-dithiole-4-carboxylic acid (1) and 2-{5-(1,3-dithiol-2-ylidene)-
[1,3]dithiolo[4,5-d][1,3]dithiol-2-ylidene}-1,3-dithiole-4,5-dicarboxylic acid (2) have been synthesized.
The electronic structure of 1 and 2 was examined from their optical absorption spectra and using
density-functional calculations.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Carboxylic acid
Hydrogen bond
Electron donor
Fused ring
Supramolecular synthon
Carboxylic acid is a useful functional group owing to the coex-
istence of acidity and hydrogen-bonding capability. Supramolecu-
lar design utilizing carboxylic acid is a promising method to
construct a desired structure and functionality, as the formation
of a salt bridge between a carboxylic and an amino group dominat-
ing designable molecular arrangement,1,2 and metal-organic
framework adopting the carboxylic acid as a ligand to form crystals
with cavities with various shapes and sizes.3,4 Moreover, the car-
boxylic acid group is advantageous in generating building blocks
for block copolymers, containing well-ordered supramolecular
fused tetrathiafulvalene skeleton was introduced. This skeleton is
known to be an attractive electron-donor molecule that provides
a highly conductive charge transfer complex owing to its highly
extended
p
-conjugate part.11,12 Although no procedure has been
reported so far for synthesizing bis-fused tetrathiafulvalene deriv-
atives with carboxylic acid or hydrogen bonded functional groups,
they have great potential in the construction of novel electroactive
supramolecules. Furthermore, the electronic properties of our tar-
get molecules, bis-fused tetrathiafulvalene carboxylic acid (1), and
dicarboxylic acid (2) (Fig. 1) are of interest, because the introduc-
tion of carboxylic acid groups is expected to extend the degree of
assembly.5,6 On the other hand,
p-conjugate molecules are fre-
quently used in molecular design to obtain desired electroactive
p-conjugation of the bis-fused TTF ring, should influence the mol-
functionalities, such as a high electrical conductivity expected from
ecule’s electronic properties owing to their electron-withdrawing
property. Measurement of the optical absorption spectra and den-
sity-functional calculations provide fundamental information on
the electronic properties of our target molecules.
Compound 1 was synthesized adopting a phosphite-mediated
cross-coupling of a 1,3-dithiole-2-thione monocarboxylate unit 4
and a tricyclic carbonyl unit 9, as shown in Scheme 1. Monocarb-
oxylate 4 was prepared from commercially available dimethyl
1,3-dithiole-2-thione-4,5-dicarboxylate 3, following the method
reported by Pittman et al.:13 an acid-catalyzed hydrolysis of
the methyl ester, monodecarbonylation of the dicarboxylic acid,
the overlap of
-conjugate molecules possessing electron-donating capability is a
hot topic in the development of novel electroactive materials.7,8
Extension of the -conjugated part is an advantageous strategy
p-orbital. Introduction of carboxylic acid groups into
p
p
for obtaining superior electronic properties with a corresponding
decrease in the energy gap between the highest occupied molecu-
lar orbital (HOMO) and the lowest occupied molecular orbital
(LUMO). However, the introduction of carboxylic acid groups with
a polar functionality to nonpolar p-conjugated molecules compli-
cates the solubility behavior, and therefore, only a limited number
of electroactive molecules are available for a supramolecular syn-
thon, such as tetrathiafulvalene9 and thiophene.10
In this Letter, we describe the synthesis of novel electroactive
molecules with mono- and dicarboxylic acid groups, where a bis-
⇑
Corresponding author.
E-mail address: kobayashi.yuka@nims.go.jp (Y. Kobayashi).
Figure 1. Target molecules: 1 and 2.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.04.064

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T. Terauchi et al. / Tetrahedron Letters 53 (2012) 3277–3280
Scheme 1. Synthesis of 1. Reagents and conditions: (a) aq HCl, AcOH, reflux, 2 h, 93% for dicarboxylic acid; (b) neat, 170 oC, 15 min, 84% for monocarboxylic acid; (c) conc
H2SO4, MeOH, 1,2-dichloroethane, reflux, 18 h, 90%; (d) P(OMe)3, reflux, 3 h, 7: 47% based on 6, 8: 53% based on 6; (e) NaOMe in MeOH, THF, rt, 1 h; (f) Triphosgene, THF, rt,
15 h, 75% (in two steps); (g) P(OMe)3, toluene, reflux, 15 h, 41% based on 9; (h) aq LiOH, MeOH, 1,4-dioxane, THF, rt, 15 h, 91%.
followed by esterification in an overall 70% yield. Several syntheses
of tetrathiapentalene-2-one derivatives, including 9, have been re-
ported previously.14–17 Bis protected TTF 7 was prepared according
to the procedure reported by Bartlett.18 Commercially available
unsubstituted 1,3-dithiole-2-thione 5 (2.2 equiv for 6) and bis(2-
cyanoethyl)-protected 1,3-dithio1-2-one 6 were coupled in neat
trimethylphosphite at 120 °C, which then formed 7, along with
dimer 819 in yields of 47% and 53%, respectively, based on 6. The
hydrolysis of 10 at room temperature in an excess 2 N lithium
hydroxide solution to form the desired carboxylic acid donor 1 pro-
ceeded in a suspension of a large volume of mixed solvents (1,4-
dioxane/THF/MeOH/aq LiOH = 2:2:2:1), and gave 1 in a 91% yield
without the formation of any decarbonylated byproducts. The final
product, 1, had lower solubility in many solvents, but when
washed with deionized water, MeOH, and then chloroform, possi-
bly gave its pure form, which was confirmed from NMR spectros-
copy data and elemental analysis. Although the yield of the key
reaction, namely the cross-coupling reaction (4+9?10), remained
at a moderate level, the total yield from the starting materials
was as high as 13%, which is a consequence of the number of syn-
thetic steps used (five).
cross-coupled product, 7, was then converted into
9 using
excess sodium methoxide in a tetrahydrofuran–methanol solution
(10:1) at room temperature, followed by treatment with excess tri-
phosgene in tetrahydrofuran under an argon atmosphere after the
removal of any solvents involving methanol, followed by drying.17
The yield was 75%. The coupling reaction between monocarboxy-
late 4 (1.2 equiv for 9) and 1,3,4,6-tetrathiapentalen-2-one 9 with
a large excess of trimethylphosphite while refluxing in toluene
successfully afforded the bis-fused TTF monocarboxylic acid
methyl ester 10 in a 41% yield.
Bis-fused TTF derivatives, 1, 2 and 2,5-bis(10,30-dithiol-20-yli-
dene)-1,3,4,6-tetrathiapentalene (BDT-TTP), were prepared using
a step-wise transformation from 11. Complete decarboxylation
from 1115 with LiBr-HMPA gave BDT-TTP in an 84% yield, as shown
in Scheme 2, as described in the literature.15 Moreover, in this
work, alkali hydrolysis of 11 with aq LiOH provided 2 in a 98%
yield. Selective decarboxylation of 11 was expected to lead to the
In the final step, alkaline hydrolysis was carried out at room
temperature to avoid any undesired decarboxylation. Alkaline
Scheme 2. The synthesis of BDT-TTP21 and 2. Reagents and conditions: (a) LiBrꢀH2O, HMPA, 80 °C, 1 h, then 130 °C, 1 h, 84%; (b) aq LiOH, 1,4-dioxane, THF, MeOH, toluene,
DMF, rt, 3 days, 91%; (c) neat, 160 °C, 15 min; (d) LiBrꢀH2O, HMPA, 80 °C, 1 h.

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T. Terauchi et al. / Tetrahedron Letters 53 (2012) 3277–3280
3279
target molecule, 1 and thus we attempted to find a proper condi-
tion. Direct heating of 2 did not afford 1, even at 160 °C, although
these conditions are known to be effective for the selective decar-
boxylation of 1,3-dithiole-2-thione dicarboxylic acid.13 Next, we
tried the reaction using the additive, LiBr-HMPA to obtain the
monocarboxylic acid 1 at temperatures <80 °C, but only a mixture
of 10 and 2 were obtained. This is probably because of the compa-
rable reaction rates of the decarboxylation and SN2 type reactions
of the bromide ion with the second methyl group. Despite further
examination, no advantageous conditions affording pure 1 were
found. Considering the difficulty of separation using chromatogra-
phy from lower solubility of 1 and 2, Scheme 1 was selected as the
best choice to obtain pure 1.
The absorption spectra of 1 and 2 were measured in the UV–vis
region, together with the spectrum of BDT-TTP,15 as shown in Fig-
ure 2. The compounds exhibited low solubility in all solvents, so
the diffuse-reflectance spectra of powdered samples were mea-
sured, and then transformed into the absorption spectra using
the Kubelka–Munk theory.20 The relative intensity of the absorp-
tion bands among the three compounds was adjusted using the
peak occurring at k = 285 nm, corresponding to the
p
p⁄ excitation
ꢁ
of the BDT-TTP skeleton. The absorption maximum was observed
at kmax = 336 nm for BDT-TTP, at kmax = 405 nm for 1 and at
kmax = 435 nm for 2, which were all systematically shifted to longer
wavelengths. This shift indicates that the energy of intramolecular
excitation had decreased from the introduction of the carboxylic
acid groups, suggesting the carboxylic acid groups had influenced
the electronic structure of BDT-TTP moiety. The absorption bands
in 2 extended into the near-infrared region, and the intensity at
800 nm is much stronger than that of BDT-TTP and 1. By our pre-
liminary electron spin resonance (ESR) measurement of powdery
sample of 2, spin signal is active with g-value of 2.00649 at room
temperature, which is slightly larger than that of BDT-TTPÅ+ ob-
served in (TTM-TTP)I3.21 This strongly suggests the partial exis-
tence of BDT-TTPÅ+ in 2, and thus detailed ESR measurements
adopting high-frequency ESR spectrometer are in progress to fully
characterize the spin emerged in 2.
The molecular and electronic structures were examined using
density-functional calculations. All the calculations were per-
formed using the B3LYP22/cc-pVDZ employing the Gaussian 03.23
The total charge in the one-electron oxidation state of 1 and 2
was compensated for by deprotonation of the carboxylic acid. Fig-
ure 3 shows the optimized structure and the molecular orbitals at
the HOMO level for 1 and 2, and BDT-TTP in the closed-shell and
one-electron oxidation states, respectively.
Figure 3. Top and side views of HOMO of 1, 1Å, 2, 2Å and BDT-TTP and (BDT-TTP)Å+
calculated with B3LYP/cc-pVDZ.
,
consistent with the shift in kmax toward longer wavelengths. The
shape of the BDT-TTP moiety in 1 and 2 in the closed-shell state
is analogous to pristine BDT-TTP. In sharp contrast, the molecular
shape in the one-electron oxidation state, namely 1Å and 2Å, was sig-
nificantly different from that of BDT-TTPÅ+, which is planar from the
acquisition of aromaticity. Planarity was only observed on one side
of the fused ring in 1Å and 2Å, where
p-conjugation between the car-
boxylate group and the aromatic ring is more effective than that in
the closed-shell state. The spin density was localized on the oxygen
atom of the carboxylate group and the oxygen atom of the BDT-TTP
moiety in 1Å and was delocalized over the entire molecule in 2Å.
These calculations demonstrate the strong influence of the carbox-
ylic acid group on the electronic properties and facile oxidation,
especially in 2, which suggest high potential for constructing a vari-
ety of supramolecular electroactive materials by adopting these
synthons.
The HOMOs of 1 and 2 in the closed-shell state, are extended
into the carbon atom of the carboxylic acid groups, which is
In conclusion, we have reported on the synthesis of 1 and 2 with
total yields of 13% in five steps and 23% in five steps, respectively.
Optical absorption spectra and density-functional calculations
have revealed that the fused TTF and mono- and dicarboxyl groups
are highly conjugated, and demonstrate their potential as synthons
controlling both structural and electroactive properties in supra-
molecular design.
Synthetic procedure for 10, 1 and 2
Methyl 2-(5-(1,3-Dithiol-2-ylidene)-[1,3]dithiolo[4,5-d][1,3]-
dithiol-2-ylidene)-1,3-dithiole-4-carboxylate (10):
7 (45.8 mg,
0.238 mmol) and 9 (58.4 mg, 0.198 mmol) were suspended in a
mixture of trimethyl phosphite (3 ml) and toluene (3 ml). After
stirring at 120 °C for 15 h, the reaction mixture was allowed to cool
to room temperature and then diluted with n-hexane (6 ml). After
the reaction mixture was cooled to 5 °C for 2 h, precipitate formed
Figure 2. UV–vis absorption spectra of 1, 2 and BDT-TTP.15

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T. Terauchi et al. / Tetrahedron Letters 53 (2012) 3277–3280
was collected by filtration using a membrane filter (H010A047A;
ADVANTEC) and washed with toluene, MeOH, and chloroform.
The polycrystalline solid was dried in vacuo to afford brown crys-
tals of 10 (35.8 mg, 41%). 1H NMR (600 MHz, DMSO-d6): d 3.76 (s,
3H), 6.80 (s, 2H), 7.88 (s, 1H); Anal. Calcd for C12H6 O2S8: C, 32.85;
H, 1.38. Found: C, 32.47; H, 1.18.
Acknowledgment
This study was supported by ‘NEXT program’ of the Ministry of
Education, Culture, Sports, Science and Technology (MEXT), Japan.
References and notes
2-{5-(1,3-Dithiol-2-ylidene)-[1,3]dithiolo[4,5-d][1,3]dithiol-2-
ylidene}-1,3-dithiole-4-carboxylic acid (1): 10 (125 mg, 0.285
mmol) was suspended in a mixture of 1,4-dioxane (50 ml), THF
(50 ml), and MeOH (50 ml). Then, 2 N LiOH (28.5 ml, 57.0 mmol)
was added to the mixture. After vigorously stirring at room
temperature for 15 h, 2 N HCl (28.5 ml) was added slowly. The
mixture was acidified to pH 2–3 (a volume of 2.0 ml of 2 N HCl
was added). After stirring at room temperature for 20 min, the
precipitate formed was collected by filtration using a membrane
filter (H010A047A; ADVANTEC) and washed with deionized
water, MeOH, and chloroform. The resulting polycrystalline
solid was dried in vacuo to afford dark red crystals of 1 (110 mg,
91%). 1H NMR (600 MHz, DMSO-d6): d 6.80 (s, 2H), 7.73 (s, 1H);
Anal. Calcd for C11H4 O2S8: C, 31.11; H, 0.95. Found: C, 30.76; H,
0.82.
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ylidene}-1,3-dithiole-4,5-dicarboxylic acid (2): 1115 (20 mg,
0.0403 mmol) was suspended by a mixture of 1,4-dioxane (4 ml),
THF (2 ml), MeOH (2 ml), toluene (2 ml), and DMF (1 ml), and then
2 N LiOH (800
orously stirring at room temperature for 3 days, 2 N HCl (800
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water, MeOH, and chloroform. The resulting polycrystalline solid
was dried in vacuo to afford dark brown crystals 2 (17.2 mg,
91%). 1H NMR (600 MHz, DMSO-d6): d 6.79 (s, 2H); Anal. Calcd
for C12H4O4S8: C, 30.75; H, 0.86. Found: C, 30.79; H, 1.19.
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