Rapid synthesis and fluorous-phase purification of α-perfluorohexyloligothiophenes

Article abstract of DOI:10.1016/j.tetlet.2006.11.165

A high-throughput methodology that facilitates the synthesis, purification and characterisation of π-conjugated oligothiophenes has been developed. α-Perfluorohexyltetrathiophene was synthesised by sequential α-bromination and microwave promoted Stille cross-coupling reactions. Each synthetic transformation was followed by a fluorous solid-phase extraction (F-SPE) procedure to isolate the desired α-perfluorohexyloligothiophene. After a single F-SPE, each oligomer gave essentially one peak by GC-MS, which enabled stepwise growth of a tetrathiophene with no additional purification of the intermediate building blocks required. We anticipate that microwave accelerated synthesis in conjunction with fluorous-phase purification of π-conjugated systems will find generic application in the high-throughput parallel-synthesis of novel organic materials for semiconductor applications.

Full text of DOI:10.1016/j.tetlet.2006.11.165

Tetrahedron Letters 48 (2007) 1045–1047
Rapid synthesis and fluorous-phase purification of
a-perfluorohexyloligothiophenes
Mark C. McCairn and Michael L. Turner*
School of Chemistry, The University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom
Received 10 November 2006; accepted 28 November 2006
Available online 22 December 2006
Abstract—A high-throughput methodology that facilitates the synthesis, purification and characterisation of p-conjugated oligo-
thiophenes has been developed. a-Perfluorohexyltetrathiophene was synthesised by sequential a-bromination and microwave
promoted Stille cross-coupling reactions. Each synthetic transformation was followed by a fluorous solid-phase extraction (F-SPE)
procedure to isolate the desired a-perfluorohexyloligothiophene. After a single F-SPE, each oligomer gave essentially one peak
by GC–MS, which enabled stepwise growth of a tetrathiophene with no additional purification of the intermediate building blocks
required. We anticipate that microwave accelerated synthesis in conjunction with fluorous-phase purification of p-conjugated sys-
tems will find generic application in the high-throughput parallel-synthesis of novel organic materials for semiconductor
applications.
Ó 2006 Elsevier Ltd. All rights reserved.
High-throughput synthesis, purification and character-
isation of p-conjugated systems would facilitate the dis-
covery of novel organic materials for semiconductor and
strategy in which a thiophene residue is attached cova-
lently to an insoluble support via a linker group. This
thiophene can then be coupled sequentially with addi-
tional thiophene monomers to generate an oligothio-
1
optoelectronic applications. Oligothiophenes have
5
attracted great interest as organic semi-conducting
components in thin film transistor devices due to their
chemical/environmental stability, high carrier mobilities
phene of desired length. Following each synthetic
transformation the oligothiophene, tethered to the
solid-support, is separated and purified simultaneously
from by-product(s) and excess reagent(s) by simple
washing and filtration procedures. However, there are
several disadvantages associated with solid-phase syn-
thesis. The unfavourable heterogeneous reaction kinet-
ics necessitates the use of a large excess of reagent(s)
to ensure a complete reaction. This can be problematic
as selective a-bromination of thiophene immobilised
on a polystyrene based resin may only be achieved with
N-bromosuccinimide (NBS) in a stoichiometric amount,
2
and excellent on/off ratios.
Generally, oligothiophenes are synthesised by palla-
3
dium-catalysed cross-coupling reactions. These reac-
tions have the inherent limitation of a slow conversion
to product and can generate significant levels of impu-
rity. Reaction times for palladium-catalysed cross-
coupling reactions can be reduced considerably by
microwave dielectric heating of the reaction mixture,
which heats the reaction mixture homogeneously by
coupling between the electromagnetic radiation and
6
excess reagent leading to multiple bromination. In
addition, reaction conditions must be optimised from
the solution-phase to the solid-phase and intermediate
compounds must be cleaved from the insoluble-support
4
the molecular dipoles of the solvent(s)/reagent(s).
7
Purification of oligothiophenes for use in organic elec-
tronic devices generally requires extensive chromato-
graphic separation. This time-consuming process may
be circumvented by employing a solid-phase synthetic
to be analysed using conventional techniques.
There is an imperative need for a generic high-through-
put methodology that facilitates the synthesis, purifica-
tion and characterisation of p-conjugated systems,
which circumvents the limitations that are associated
with both solution-phase and solid-phase techniques.
Fluorous-phase techniques integrate the advantages of
both solid-phase purification and solution-phase synthe-
Keywords: Oligothiophene; Microwave synthesis; Fluorous phase.
*
Corresponding author. Tel.: +44 161 275 4625; fax: +44 161 275
273; e-mail: michael.turner@manchester.ac.uk
4
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.11.165

1046
M. C. McCairn, M. L. Turner / Tetrahedron Letters 48 (2007) 1045–1047
8
sis and characterisation. In this approach, a fluorinated
tagged compound is reacted with a stoichiometric
amount of reagent(s) using solution-phase reaction con-
ditions. Following each synthetic transformation the
fluorinated compound is separated selectively from
non-fluorinated molecules by employing a fluorous sep-
a-Perfluorohexyloligothiophenes 1–5 were isolated
following each synthetic transformation by employing
a F-SPE procedure. The crude product mixture of each
reaction was loaded onto a F-SPE cartridge and washed
with methanol/water (4:1) to elute non-fluorinated
material. The F-SPE cartridge was then washed with
methanol and tetrahydrofuran to elute the desired a-
perfluorohexyloligothiophene 1–5, which was confirmed
rapidly by gas chromatography–mass spectrometry
(GC–MS) (Fig. 1).
9
aration media. For instance, fluorinated-compounds
>60% fluorine by molecular weight) can be efficiently
(
partitioned into fluorous solvent from either organic
or aqueous solvent in a liquid–liquid extraction proce-
dure and fluorous-silica gel retains fluorinated-com-
pounds (>40% fluorine by molecular weight) by
selective adsorption. In a typical fluorous-solid phase
extraction (F-SPE) procedure, the crude reaction
mixture (5–15% weight of fluorous-silica gel) is loaded
onto fluorous-silica gel and washed with a fluorophobic
solvent to elute non-fluorinated compound(s) and then
washed with a fluorophilic solvent to elute the
fluorinated compound(s), which may be analysed using
conventional solution-phase techniques without prior
The a-perfluorohexyloligothiophenes 1–5 were isolated
by a single SPE with sufficient purity to give essentially
one peak in the chromatograph and a concomitant
increase in retention time with increase in molecular
mass. This highly efficient methodology enables the
stepwise growth of tetrathiophenes with no additional
purification of the intermediate oligomers required.
The optical absorption and emission spectra of 5 were
9
ABS
max
PL
max
cleavage of the fluorous tag.
determined both in solution ðk
¼ 396 nm; k
¼
ABS
max
4
88 nmÞ and the solid state ðk
¼ 346 nm and
ABS
PL
A high-throughput approach for the preparation of oli-
gothiophenes using fluorous-phase chemistry is reported
for the first time. This approach is demonstrated by
the preparation of a-perfluorohexyltetrathiophene 5
k
¼ 450 nm; k
¼ 559 nmÞ (Fig. 2). Broad, unstruc-
max
tured signals are observed, consistent with the high
degree of rotational freedom between individual
thiophene residues both in the ground and excited
(
Scheme 1). Related a,x,-perfluorohexyl substituted
states. A large molar extinction coefficient (e =
ꢀ
1 3
ꢀ1
oligothiophenes have been shown to be excellent n-type
organic semiconductors (l > 0.2 cm V
42,996 mol dm cm ) indicates that these signals
2
ꢀ1 ꢀ1 10
*
s
).
originate from the allowed p–p transition associated
with the tetrathiophene core. The blue shift (50 nm) of
the maximum absorption in the solid-state relative to
the solution state is a consequence of H aggrega-
Initially, Ullman type reaction conditions were em-
ployed to couple bromobithiophene with 1-iodoperflu-
orohexane to provide a-perfluorohexylbithiophene 1
1
0a,12
tion.
The interaction between molecules of 5 with
1
1
(
78%). Bithiophene 1 was then reacted with a solution
their long axis parallel results in coupling of the transi-
tion dipoles, which leads to Davydov splitting of the
excited level into two excitation bands. The major
absorption signal (346 nm) corresponds to the allowed
high energy transitions and the small signal (450 nm)
of NBS in N,N-dimethylformamide (DMF) to afford the
1
0a
corresponding bromide 2 (78%).
moted Stille cross-coupling reaction between bromide
and 2-(tributylstannyl)thiophene proceeded smoothly
A microwave pro-
2
and rapidly (1 min) to give trithiophene 3 (90%). a-Bro-
mination and Stille cross-coupling reactions were
repeated sequentially to furnish the corresponding
bromide 4 (88%) and finally the desired tetrathiophene
corresponds to low-energy transitions that are forbid-
op
den. The optical band gap ðE Þ was estimated from
g
the intercept of the normalised absorption and emission
op
spectra both in solution ðE ¼ 2:79 eVÞ and the
g
op
5
(54%).
solid-state ðE ¼ 2:49 eVÞ. In addition, the electro-
g
chemical behaviour of 5 was investigated by cyclic vol-
tammetry to determine the energy level of the highest
1
3
occupied molecular orbital (HOMO). The voltammo-
i
F C(CF ) -I
3
2 5
F C(CF )
H
3
2 5
S
1
0
0
.1
.9
.7
1
2
3
4
5
n
1
: n=2
ii
F C(CF )
H
F C(CF )
2 5
Br
3
2 5
3
S
S
n
n
1
: n=2, 3 : n=3
2 : n=2, 4 : n=3
0.5
0
0
.3
.1
iii
F C(CF )
Br
F C(CF )
2 5
H
3
2 5
3
S
S
n
n
2
: n=2, 4 : n=3
3 : n=3, 5 : n=4
-0.1
Scheme 1. Synthesis of a-perfluorohexyloligothiophenes 1–5. Reagents
and conditions: (i) 5-bromo-2,2 -bithiophene, Cu, DMSO, 125 °C; (ii)
8
9
10
11
12
13
14
15
16
17
18
0
Retention Time / minutes
3 4 6 5
NBS, DMF and (iii) 2-(tributylstannyl)thiophene, Pd(PPh ) , ClC H ,
lW, 190 °C, 150 PSI, 1 min.
Figure 1. Gas-chromatogram of a-perfluorohexyloligothiophenes 1–5.

M. C. McCairn, M. L. Turner / Tetrahedron Letters 48 (2007) 1045–1047
1047
found, in the online version, at doi:10.1016/
j.tetlet.2006.11.165.
1
.8
.6
.4
.2
0
0
0
0
0
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Supplementary data
Experimental procedures and spectroscopic data. Sup-
plementary data associated with this article can be