Synthesis and Crystal Structure of a Tubular Sexithiophene

Article abstract of DOI:10.1021/ol016122t

(matrix presented) The synthesis of a rigid, tubular sexithiophene is reported. Close intermolecular Cl...-Cl interactions play a significant role in defining the crystal structure.

Full text of DOI:10.1021/ol016122t

ORGANIC
LETTERS
2001
Vol. 3, No. 13
2129-2131
Synthesis and Crystal Structure of a
Tubular Sexithiophene
Michael J. Marsella,* Kunsang Yoon, and Fook S. Tham
Department of Chemistry, UniVersity of California at RiVerside,
RiVerside, California 92521
michael.marsella@ucr.edu
Received May 14, 2001
ABSTRACT
The synthesis of a rigid, tubular sexithiophene is reported. Close intermolecular Cl‚‚‚Cl interactions play a significant role in defining the
crystal structure.
In 1978, Kauffmann reported the synthesis of both tetra-
[2,3-thienylene] and hexa[2,3-thienylene] (24% and 4%
isolated yield, respectively; see Figure 1) via the CuCl2-
promoted oxidative homocoupling of 3,3′-dilithio-2,2′-
bithiophene.1 Despite their novel structure, these cyclic
oligothiophenes disappeared from the literature for almost
20 years. During this hiatus, the interest in π-conjugated
materials with novel topologies increased dramatically.2
Beginning in 1999, we focused our attention on the afore-
mentioned cyclic oligothiophenes, having reported tetra[2,3-
thienylene] as a building block for both molecular electro-
mechanical actuators (“molecular muscles”)3 and extended
double helices.4 In addition, Iyoda recently reported the
synthesis of planar variants of tetra[2,3-thienylene].5 Al-
though tetra[2,3-thienylene] is conformationally analogous
to its parent [8]annulene, cyclooctatetraene, expansion of the
macrocycle by one extra bithiophene unit yields the rigid
(1) Kauffmann, T.; Greving, B.; Kriegesmann, R.; Mitschker, A.;
Woltermann, A. Chem. Ber. 1978, 111, 1330-1336.
(2) For recent reviews, see: (a) Scott, L. T.; Bronstein, H. E.; Preda, D.
V.; Ansems, R. B. M.; Bratcher, M. S.; Hagen, S. Pure Appl. Chem. 1999,
71, 209-219. (b) Rabideau, P. W.; Sygula, A. Acc. Chem. Res. 1996, 29,
235-242. (c) Kroto, H. W.; Heath, J. R.; O’Brien, S. C.; Curl, R. F.;
Smalley, R. E. Nature 1985, 318, 162. (d) Martin, N.; Sanchez, L.; Illescas,
B.; Perez, I. Chem. ReV. 1998, 98, 2527-2547. (e) Ajayan, P. M. Chem.
ReV. 1999, 99, 1787-1799. (f) For a recent report of all R-conjugated cyclic
oligothiophenes, see: Kromer, J.; Rios-Carreras, I.; Fuhrmann, G.; Musch,
C.; Wunderlin, M.; Debaerdemaeker, T.; Mena-Osteritz, E.; Bauerle, P.
Angew. Chem., Int. Ed. Engl. 2000, 39, 3481-3486.
(3) Marsella, M. J.; Reid, R. J. Macromolecules 1999, 32, 5982-5984.
(4) Marsella, M. J.; Kim, I. T.; Tham, F. J. Am. Chem. Soc. 2000, 122,
974-975.
(5) Kabir, S. M. H.; Miura, M.; Sasaki, S.; Harada, G.; Kuwatani, Y.;
Yoshida, M.; Iyoda, M. Heterocycles 2000, 52, 761-774.
Figure 1. Three cyclic oligothiophenes and the hypothetical self-
assembled nanotube, compound 2nt.
10.1021/ol016122t CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/02/2001

and tubular hexa[2,3-thienylene], compound 1. Herein we
report the synthesis and crystal structure of the hexachloro
derivative of compound 1, compound 2.
Scheme 1a
Our impetus for pursuing the hexachloro derivative of
compound 1 came, in part, from the desire to investigate
how intermolecular Cl‚‚‚Cl interactions would dictate solid-
state packing, as such interactions traditionally play a
significant role in determining crystal structures.6,7 In the case
of compound 2, each of the two ends of the tubular molecule
possess three coplanar chlorine atoms that should act to orient
adjacent molecules. In one possible scenario, Cl‚‚‚Cl interac-
tions could linearly align the long molecular axis of 2 along
the imaginary line formed by joining the centroid of each
molecule. As depicted in Figure 1 by the hypothetical
supramolecular assembly, 2nt, this interaction would yield a
supramolecular nanotube motif.8 Alternatively, C-Cl‚‚‚Cl-C
interactions may radiate in an approximately linear sense
(with respect to the C-Cl bond) to yield a zigzag-type
arrangement (Figure 2). In this report, the latter of the two
motifs is observed.
a Reagents: (a) 2.1 equiv of NBS, DMF, 84%; (b) 2.4 equiv of
NCS, DMF, 80 °C, 90%; (c) (i) 1.05 equiv of n-BuLi, THF, -78
°C, (ii) i-PrOH, -78 °C, 76%; (d) (i) 2.1 equiv of n-BuLi, Et2O,
-78 °C, (ii) Bu3SnCl; (e) Pd(PPh3)4, toluene, 27%; (f) 2.15 equiv
of NBS, DMF, 60 °C, 98%; (g) (i) 2.0 equiv of n-BuLi, Et2O, -78
°C, (ii) CuCl2, Et2O, 20%.
facile lithium-halogen exchange;11 and (3) arylbromides
typically undergo palladium- and nickel-catalyzed cross-
coupling faster than aryl chlorides.12,13 With specific regard
to premise 1, the reactivity of 3,3′-bithiophene toward
electrophillic attack follows the order 2 ) 2′ > 5 ) 5′ > 4
) 4′.3 Thus, bromination of 3,3′-bithiophene with 2 equiv
of NBS, followed by chlorination with 2 equiv of NCS,
yields the key building block, compound 3. Compound 3
serves as both the central bithiophene unit of linear hexathie-
nylene, compound 7, as well as the precursor to the two
terminal bithiophene moieties, compound 5 (Scheme 1).
Unlike the numerous reports demonstrating facile cross-
coupling of R,R′-oligo- and polythiophenes,14-16 the assembly
of hexathienylene 6 via the cross-coupling of 3 and 5 was
troublesome. In our hands, the optimized procedure (27%
yield of 617) entailed a Stille-type cross-coupling using
toluene as solvent and Pd(PPh3)4 as catalyst (premise 3,
Scheme 1). Of the many conditions screened during this
optimization, it is interesting to note that although zerovalent
Figure 2. X-ray crystal structure of compound 2 showing 3.452
Å Cl‚‚‚Cl interactions (dashed lines). Disordered THF has been
omitted for clarity.
Given the low reported yield of compound 1, we wished
to pursue an alternative synthetic strategy. In analogy to our
synthesis of regioregular tetra[2,3-thienylene]s via cyclization
of the corresponding linear tetrathiophene,3 we envisioned
synthesizing compound 2 via its parent linear sexithiophene.
The synthesis of compound 2 is shown in Scheme 1 and is
built on the following three premises: (1) the R-thienyl
position is more reactive than the â-thienyl position toward
electrophillic attack9 and Pd(0) insertion (oxidative addi-
tion);10 (2) aryl bromides, but not aryl chlorides, undergo
(10) Bussolari, J. C.; Rehborn, D. C. Org. Lett. 1999, 1, 965-967.
(11) March, J. AdVanced Organic Chemistry: Reactions, Mechanisms,
and Structure, 4th ed.; Wiley: New York, 1992.
(12) Colon, I.; Kelsey, D. R. J. Org. Chem. 1986, 51, 2627-2637.
(13) Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang,
P. J., Eds.; Wiley-VCH: New York, 1998.
(14) McCullough, R. D.; Williams, S. P. J. Am. Chem. Soc. 1993, 115,
11608-11609.
(15) McCullough, R. D.; Lowe, R. D.; Jayaraman, M.; Anderson, D. L.
J. Org. Chem. 1993, 58, 904-912.
(6) Desiraju, G. R. Crystal Engineering: The Design of Organic Solids;
Elsevier: New York, 1989; Vol. 54.
(16) Chen, T. A.; Rieke, R. D. J. Am. Chem. Soc. 1992, 114, 10087-
10088.
(7) Ramasubbu, N.; Parthasarathy, R.; Murray-Rust, P. J. Am. Chem.
Soc. 1986, 108, 4308-4314.
(17) Compound 6. A room-temperature toluene solution (12 mL) of
compound 5 (2.45 mmol), compound 3 (1.22 mmol), and Pd(Ph3P)4 (0.049
mmol) was stirred for 1 h and then heated to 100 °C for 12 h. The reaction
mixture was cooled and extracted with brine/Et2O. Compound 6 was isolated
from the crude by drying the organic extract over MgSO4, filtering, removing
volatile components under reduced pressure, and purifying by silica gel
column chromatography (hexane). Compound 6 was isolated as a yellow
(8) For a review of self-assembled nanotubes, see: Bong, D. T.; Clark,
T. D.; Granja, J. R.; Ghadiri, M. R. Angew. Chem., Int. Ed. 2001, 40, 988-
1011.
(9) Gupta, R. R.; Kumar, M.; Gupta, V. Heterocyclic Chemistry;
Springer: Berlin, New York, 1998.
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Org. Lett., Vol. 3, No. 13, 2001

nickel cross-coupling between 2- or 3-thienylmagnesium-
bromide and 2- or 3-bromothiophene gives nearly quantita-
tive yield of the corresponding bithiophene,18-20 the analo-
gous reaction to prepare compound 6 is unproductive.
As a final step, compound 221 was prepared in 20%
isolated yield (racemic) by lithium-halogen exchange of the
two bromines of compound 722 (achiral) with butyllithium
(premise 2), followed by oxidative coupling with CuCl2. In
agreement with Kauffmann’s observations, product 2 could
not be obtained when Fe3+ oxidants (FeCl3 or Fe(acac)3) were
used.1
Compound 2 is a colorless solid (onset of absorption at
320 nm), indicating poor π-orbital overlap within the [12]-
annulene equator of the macrocycle. This is commensurate
with the experimentally determined 102.7° average value of
the S-C-C-S dihedral angle (determined by X-ray crystal-
lography). Unlike tetra[2,3-thienylene], this angle is relatively
fixed in a twisted s-trans conformation. Compound 2 exhibits
relatively good solubility in chlorinated solvents and in THF.
X-ray crystallographic data for single crystals of compound
2 grown in CCl4 and CH2Cl2 could not be sufficiently refined
but did show unequivocal evidence of solvent inclusion via
Cl‚‚‚Cl interactions between solvent and substrate. In general,
it was found that the crystal morphology of compound 2
varied dramatically as a function of solvent, and only
crystallization from THF consistently provided plates suitable
for X-ray analysis.
Figure 2 shows the crystal structure of compound 2. Note
that included molecules of disordered THF have been omitted
for clarity. The dashed lines in Figure 2 represent 3.452 Å
Cl‚‚‚Cl interactions, of which there are four per molecule.
With respect to these interactions, compound 2 interacts with
four nearest neighbors to yield the aforementioned zigzag
motif, as depicted in Figure 2. The remaining two Cl‚‚‚Cl
interactions (not shown) extend along the b-axis of the unit
cell, at a length of 3.706 Å. Having established that
intermolecular Cl‚‚‚Cl interactions in this system are sig-
nificant directing entities, we attempted to obtain an alterna-
tive packing motif by avoiding solvent inclusion and thus
performed a sublimation of compound 2. Although com-
pound 2 sublimed without degradation, it did not yield
crystals of X-ray quality. Our investigations into other
polymorphs of compound 2 continue.
In addition to influencing solid-state structure, the place-
ment of a chlorine at each of the six peripheral R-thienyl
positions of compound 2 was also pursued in an effort to
provide reactive sites for further synthetic transformations,
such as covalent extension of the macrocycle via cross-
coupling chemistry.23-25 Furthermore, the synthesis estab-
lished herein should be readily modified to prepare the parent
hexa[2,3-thienylene], compound 1. In this regard, it is worth
noting that compound 1 serves to hold three (twisted) s-trans
bithiophene units rigidly in three-dimensional space. The
electrochemical polymerization of such a building block
should result in a highly rigid, porous, and cross-linked
polythiophene; ideally providing a polymer network some-
what analogous to that observed in the crystal structure of
2. Such studies are currently under investigation.
powder in 27.0% yield. 1H NMR (CDCl3) δ 6.75 (s, 2H), 6.59 (d, 2H, J )
1.54 Hz), 6.41 (d, 2H, J ) 2.05), 6.27 (s, 2H). 13C NMR (CDCl3) δ 134.86,
134.15, 133.77, 132.33, 131.03, 130.88, 129.01, 128.61, 128.10, 127.48,
126.19, 121.33. HRMS calcd 697.7081, obsd 697.7057.
(18) Tamao, K.; Kodama, S.; Nakajima, I.; Kumada, M. Tetrahedron
1982, 38, 3347-3354.
(19) Khor, E.; Siu, C. N.; Hwee, C. L.; Chai, S. Heterocycles 1991, 32,
1805-1812.
Acknowledgment. This work was supported by the
donors of the Petroleum Research Fund (administered by
the American Chemical Society), DuPont (Young Professor
Grant to M.J.M.), and the University of California at
Riverside
(20) Jayasuriya, N.; Kagan, J. Heterocycles 1986, 24, 2261-2264.
(21) Compound 2. To a solution of compound 7 (0.499 g, 0.581 mmol)
in diethyl ether (29 mL) was added dropwise n-butyllithium (0.75 mL of
1.58 M solution, 1.18 mmol) at -65 °C. After the mixture was stirred at
-40 °C for 1 h, the cold solution was cannulated slowly (0.3 mL/min) to
a stirred, room-temperature solution of CuCl2 in diethyl ether (29 mL). After
20 h of stirring at room temperature, the mixture was quenched with water
and filtered over Celite. The two layers were separated, and the aqueous
layer was extracted with diethyl ether. The combined organic extracts were
washed with water and brine solution and dried over MgSO4. The solvent
was removed under reduced pressure, and the crude was purified by
fractional recrystallization (CH2Cl2/hexanes) to provide compound 2 as a
white powder in 20.0% yield. 1H NMR (CDCl3) δ 6.70 (s, 6H). Crystal
structure is shown in Figure 2, and crystallographic data has been deposited
in the Cambridge Crystallographic Data Centre Database.
Supporting Information Available: Details of X-ray
determination. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL016122T
(23) Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 2719-2724.
(24) Lipshutz, B. H.; Blomgren, P. A. J. Am. Chem. Soc. 1999, 121,
(22) Compound 7. 1H NMR (CDCl3) δ 6.90 (s, 2H), 6.20 (s, 2H), 6.13
(s, 2H). 13C NMR (CDCl3) δ 134.80, 133.65, 132.29, 131.65, 131.45,
130.14, 129.77, 128.71, 128.35, 127.68, 127.37, 107.62. HRMS calcd
855.5271, obsd 855.5297.
5819-5820.
(25) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020-
4028.
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