Expanding tetra[2,3-thienylene]-based molecular muscles to larger [4n]annulenes

Article abstract of DOI:10.1055/s-2002-32529

The synthesis, X-ray structure, and predicted redox-induced conformational dynamics of a thiophene-fused [12]annulene is reported. Regiospecific halogenation of the thiophene ring system and transition-metal catalyzed cross-couplings are key elements in the synthetic strategy. It is predicted (B3LYP/6-31G*) that redox-induced conformational changes yield significant dimensional changes in this annulene, thus establishing it as a candidate for single molecule actuation.

Full text of DOI:10.1055/s-2002-32529

SHORT PAPER
1133
Expanding Tetra[2,3-thienylene]-Based Molecular Muscles to Larger
[4n]Annulenes
Expanding
T
etra[2,3-th
i
ienyle
c
M
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olecular
M
a
uscles toLa
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[4
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J. Marsella,* Guangzhe Piao, Fook S. Tham
Department of Chemistry, University of California, Riverside, Riverside, CA 92521-0403, USA
E-mail: michael.marsella@ucr.edu
Received 1 March 2002
ca. 24 kcal/mol. Calculations at the PM3 level of theory
predict the planar conformer of tetra(2,3-thienylene) is in-
accessible over all oxidation states from 2– to 2+. For com-
parative purposes, note that the barrier to ring inversion
Abstract: The synthesis, X-ray structure, and predicted redox-in-
duced conformational dynamics of a thiophene-fused [12]annulene
is reported. Regiospecific halogenation of the thiophene ring system
and transition-metal catalyzed cross-couplings are key elements in
the synthetic strategy. It is predicted (B3LYP/6-31G*) that redox- for the less sterically congested [8]annulene, isopropylcy-
clooctatetraene, is ca. 14.8 kcal/mol,10 while the more
induced conformational changes yield significant dimensional
changes in this annulene, thus establishing it as a candidate for sin-
gle molecule actuation.
sterically congested [8]annulene, tetra-o-phenylene, is
greater than 45 kcal/mol.11 If complete planarity ( = 0)
Key words: annulenes, thiophene, cross-coupling, actuators, mac-
rocycles
were possible in tetra(2,3-thienylene), the range of actua-
tion (d-Ca–Cb) would be 20%. However, steric crowding re-
duces this range to a predicted 6.7%.
Redox-active polymers are capable of functioning as bulk
electromechanical actuators.1 By definition, such materi-
als are capable of converting electrical energy (redox
chemistry; as opposed to chemical energy2) into a bulk di-
mensional change that can be harnessed to perform work.3
In 1999 we reported the concept of a single molecule elec-
tromechanical actuator (a so-called molecular muscle).4
As exemplified by the hypothetical poly(cyclooctatet-
raene) shown in Scheme 1, our design was based on har-
nessing the perturbation in distance, d, that occurs during
a redox-induced tub-to-planar conformational change in
an [8]annulene.5 In an effort to integrate the conforma-
tional dynamics of an [8]annulene with the favorable elec-
trochemical properties of polythiophene,6 we utilized
Kauffmann’s thiophene fused [8]annulene, tetra[2,3-thie-
nylene],7,8 as our building block. Although theoretical
calculations9 predict poly(tetra[2,3-thienylene)] to func-
tion as planned (change in d as a function of oxidation
state), the range of actuation (a function of accessible con-
formers) is limited due to steric interactions between pe-
ripheral -thienyl hydrogens (Scheme 1). Herein we
report the synthesis, X-ray structure, and anticipated con-
formational dynamics of an expanded tetra(2,3-thie-
Scheme 1
Compound 1 overcomes steric interactions between pe-
ripheral -substituents by insertion of two alkyne spacers,
thus rendering the ‘expanded’ tetrathienylene as a
thiophene-fused didehydro[12]annulene. Given that a 4n
nylene), compound 1. Theoretical calculations predict
that relieving steric congestion by expanding from an
-electron count is maintained within an elongated octago-
[8]annulene to a [12]annulene core affords a molecular
nal framework, a non-planar to planar redox-induced con-
actuator exhibiting a range of actuation more than double
formation change analogous to cyclooctatetraene is
that of tetra(2,3-thienylene)-based materials.
anticipated. Compound 1 is a regioisomer of the A-frag-
ment of the octaaryl double helix, compound 2 (Figure 1),
As stated, planarization of tetra(2,3-thienylene) is severe-
a system previously reported by us.12 The similarity be-
tween isomers allows access via a similar synthetic strat-
egy. As shown in Scheme 2, regiospecific bromination of
commercially available 2-methylthiophene with NBS is
followed by nickel catalyzed homocoupling to yield
bithiophene 4. Bromination of compound 4 is also re-
giospecific, and yields compound 5 in 72% yield. Lithi-
ly inhibited by the spatial orientation of peripheral -thie-
nyl hydrogen atoms. This fact is reflected by the relatively
high barrier for ring inversion, a value determined to be
Synthesis 2002, No. 9, 01 07 2002. Article Identifier:
1437-210X,E;2002,0,09,1133,1135,ftx,en;C10902SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1134
M. J. Marsella et al.
SHORT PAPER
um–iodine exchange converts 5 to the common building
block in this synthesis, compound 6. Diethynyl 7 is pre-
pared via standard Pd/Cu(I) catalyzed cross coupling13 of
6 with trimethylsilylacetylene (TMSA), followed by
deprotection of the TMS group (compound 8). Lastly,
product 1 is obtained in 23% isolated yield via Pd/Cu(I)
catalyzed cross-coupling of compounds 6 and 8.
Scheme 2
lated to be 9.7 kcal/mol, a value 14.3 kcal/mol lower in
energy than the parent tetra(2,3-thienylene). Interestingly,
each oxidation state of compound 1 is associated with a
unique value of and d, thus yielding a range of actuation
that may be attenuated across five unique oxidation states.
In summary, the first two steps toward improved single
molecule electromechanical actuators based on thiopene-
fused [4n]annulenes have proven successful. First, the
synthesis of an expanded tetra(2,3-thienylene), compound
1, has been developed. Second, DFT calculations predict
compound 1 to exhibit a large range in redox-induced
conformational perturbations. Specifically, an 18% di-
mensional change is predicted for 12+. This large range of
actuation is attributed, in part, to a reduction in the steric
congestion resulting from -substituent interactions in the
parent tetra(2,3-thienylene) system. The next steps in this
study will focus on the electrochemical properties of com-
pound 1, as well as its incorporation into a regiospecific
homopolymer capable of translating the aforementioned
intrinsic property of molecular electromechanical actua-
tion throughout a single polymer chain.
Figure 1 Showing compounds 1 and 2.
The X-ray crystal structure of compound 1 is shown in
Figure 1, and the twisted conformation is apparent.14 The
molecule adopts C1 symmetry, with two unique S–C–C–S
dihedral angles ( ) corresponding to 34.9 and 41.2. The
average distance, d, is equal to 8.105Å. Density Function-
al Theory (B3LYP/6-31G*) was used to model the ground
state geometry of compound 1, less the four methyl
sidechains. Figure 2 shows a comparison between bond
lengths and dihedral angles as determined by experiment
(average bond lengths) and theory. The agreement is rela-
tively good given different symmetries (C1 for X-ray and
D2 for theory), a difference that can be ascribed to packing
forces in the crystal. Having established confidence with
this level of theory, we probed the redox-induced confor-
mational changes, both and d, by modeling the 2–, 1–, 1+,
and 2+ oxidation states (all possess D2 symmetry). The re-
sults are shown in Figure 2.
All air and moisture-sensitive reactions were carried out in oven-
dried glassware using standard Schlenk techniques under an inert
atmosphere of dry nitrogen. Anhydrous solvents were dried over ac-
As can be seen from the predicted dihedral angles, a large
redox-induced conformational change from twisted
( = 36.7) to planar ( = 0.0) occurs upon two-electron
oxidation from a 4n to a 4n + 2 -electron count. The cor-
Figure 2 Bond lengths and dihedral angle, . For bond lengths, the
responding change in distance, d, is 18%. Note that this top entry corresponds to the calculated value (B3LYP/6-31G*; D2
symmetry), and the bottom entry corresponds to the average of expe-
rimentally determined values (X-ray; C1 symmetry), except in the
case of (both unique values from X-ray data are provided). All bond
lengths are reported in Å, and all dihedral angles are reported in de-
range is more than double that predicted for tetra(2,3-thie-
nylene) itself, a difference credited, in part, to a reduction
in intramolecular sterics between adjacent -thienyl posi-
tions. In further support, the barrier to inversion is calcu-
grees.
Synthesis 2002, No. 9, 1133–1135 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Expanding Tetra[2,3-thienylene]-Based Molecular Muscles to Larger [4n]Annulenes
1135
tivated alumina. Reagents were used as received from Acros, Ald-
rich, and Lancaster. Compounds 3– 8 were prepared according to
the literature methods reported for the synthesis of compound 2. 1H
and 13C NMR spectra were recorded with a Varian Inova-300 (300
MHz) spectrometer in CDCl3. UV/Vis spectra were recorded on a
Varian Cary 50Bio UV-Visible spectrophotometer. Mass spectra
and high-resolution mass spectra were performed at the Southern
California Regional Mass Spectrometry Facility (University of Cal-
ifornia at Riverside). Data for 1-ORTEP: Crystal data: size
0.35 0.33 0.26 mm-3, triclinic cell, a = 7.8365(8) Å,
13C NMR (CDCl3, 75 MHz): = 138.64, 131.69, 129.07, 118.00,
82.45, 79.94, 15.33. HRMS: Calcd for C14H10S2: 242.0224. Found:
242.0219.
UV/Vis (THF): max = 239, 282, 354 nm.
Compound 1
To a solution of CuI (0.330 g, 1.73 mmol), Ph3P(0.744g, 2.84mmol)
and tris(dibenzylideneacetone)dipalladium(0) (0.181 g, 1.01mmol)
in diisopropylamine (120 mL) was added a solution of compound 8
(0.348 g, 0.748mmol) and 6 (0.189 g, 0.748 mmol) via syringe
pump at 70 °C. The addition was done under an atmosphere of ar-
gon over 4.5 h. The reaction mixture was cooled and concentrated
in vacuo. The brown residue was extracted into Et2O, and washed
first with aq HCl (5%; 3 × 100 mL ) and then with brine (100 mL).
The organic layer was dried (MgSO4). The Et2O was removed by
rotary evaporation. The resulting crude product was purified by sil-
ica gel column chromatography (hexanes–CH2Cl2) to give 1
b = 12.5954(12) Å, c = 14.0004(13) Å,
= 63.300(2)o,
= 84.201(2)o, = 74.922(2)o, V = 1191.8(2) Å3, Z = 2, space
group P-1. A sphere of reflections was collected (Bruker
SMART1000 CCD detector, Mo X-ray). SHELXTL (Version 5.1)
software was used for phase determination and structure refine-
ment. Atomic coordinates, isotropic and anisotropic displacement
parameters of all the non-hydrogen atoms were refined by means of
a full matrix least-squares procedure on F2.
Yield: 23%; pale yellow solid.
1H NMR (CDCl3, 300 MHz): = 6.69 (d, 4 H, J = 1.2 Hz), 2.44 (d,
12 H, J = 1.2 Hz).
13C NMR (CDCl3, 75 MHz): = 139.96, 137.73, 131.76, 119.70,
90.99, 15.47.
2-Bromo-5-methylthiophene (3)
1HNMR (CDCl3, 300 MHz): = 6.86 (d, 1 H, J = 3.6 Hz), 6.54 (m,
1 H), 2.45 (d, 3 H, J = 1.2 Hz).
13C NMR (CDCl3, 75 MHz): = 141.54, 129.78, 125.69, 108.77,
15.32.
HRMS: Calcd for C24H16S4: 432.0135. Found: 432.0136.
UV/Vis (THF): max = 239, 298 nm.
HRMS: Calcd for C5H5SBr: 175.9295. Found: 175.9289.
5,5 -Dimethyl-2,2 -bithiophene (4)
1H NMR (CDCl3, 300 MHz): = 6.90 (d, 2 H, J = 3.3 Hz), 6.48 (m,
2 H), 2.48 (s, 6 H). HRMS: Calcd for C10H10S2: 194.0224.
Found:194.0230.
Acknowledgement
This work was supported by the National Science Foundation
(CHE-9974548) and DuPont (Young Professor Award to M.J.M.).
3,3 -Dibromo-5,5 -dimethyl-2,2 -bithiophene (5)
1H NMR (CDCl3, 300 MHz): = 6.74 (d, 2 H, J = 1.2 Hz), 2.49 (d,
6 H, J = 1.2 Hz).
References
13C NMR (CDCl3, 75 MHz): = 141.88, 128.93, 126.89, 111.50,
15.71.
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HRMS: Calcd for C10H8S2Br2: 349.8434. Found: 349.8434.
3,3 -Diiodo-5,5 -dimethyl-2,2 -bithiophene (6)
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(7)
1H NMR (CDCl3, 300 MHz): = 6.71 (d, 2 H, J = 1.2 Hz), 2.42 (d,
6 H, J = 1.2 Hz), 0.28 (s, 18 H).
HRMS: Calcd for C20H26S2Si2: 386.1014. Found: 386.1136.
3,3 -Diethynyl-5,5 -dimethyl-2,2 -bithiophene (8)
1H NMR (CDCl3, 300 MHz): = 6.76 (d, 2 H, J = 0.9 Hz), 3.33 (s,
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Synthesis 2002, No. 9, 1133–1135 ISSN 0039-7881 © Thieme Stuttgart · New York