Selective direct arylation of 3-bromo-2-methylthiophene: A building-block for electro- and photoactive organic materials

Article abstract of DOI:10.1016/j.tetlet.2013.05.015

Selective direct arylation of 3-bromo-2-methylthiophene with aryl bromides to form a library of 2-aryl-4-bromo-5-methylthiophenes is demonstrated. The reaction yields varied from 27-63%. The inherent selectivity observed is attributed to the lack of oxidative insertion of the bromine in 3-bromo-2-methylthiophene. This method will be useful for the facile preparation of functional organic electronic materials.

Full text of DOI:10.1016/j.tetlet.2013.05.015

Tetrahedron Letters 54 (2013) 3785–3787
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Selective direct arylation of 3-bromo-2-methylthiophene:
a building-block for electro- and photoactive organic materials
⇑
George Vamvounis , David Gendron
Centre for Organic Electronics & Photonics, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia
a r t i c l e i n f o
a b s t r a c t
Article history:
Selective direct arylation of 3-bromo-2-methylthiophene with aryl bromides to form a library of 2-aryl-4-
bromo-5-methylthiophenes is demonstrated. The reaction yields varied from 27–63%. The inherent
selectivity observed is attributed to the lack of oxidative insertion of the bromine in 3-bromo-2-methyl-
thiophene. This method will be useful for the facile preparation of functional organic electronic materials.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 20 March 2013
Revised 21 April 2013
Accepted 3 May 2013
Available online 11 May 2013
Keywords:
Oligothiophenes
Direct arylation
Organic electronics
Organic electro- and photoactive materials have flourished be-
cause of their applicability in the next generation of electronic de-
vices such as transistors,1 solar cells,2 sensors,3 and light emitting
diodes.4 Therefore, simple, non-toxic, and inexpensive synthetic
methods are in high-demand to produce these materials. However,
traditional methods used for the preparation of electroactive mate-
rials including Suzuki–Miyaura, Stille, Kumada, and Reike cou-
plings require the use of dangerous and water-sensitive
reagents.5 Direct-arylation by C–H activation is an emerging syn-
thetic methodology. It is superior compared to traditional routes
leading to organic materials in fewer synthetic steps and higher
overall yields without the use of water-sensitive and dangerous re-
agents, and avoids the production of toxic or unstable intermedi-
ates, such as tin and boronic acid compounds.5,6 This
communication investigates the reactivity of commercially avail-
able 3-bromo-2-methylthiophene with various aryl bromides
using direct arylation, and demonstrates a selective C–H activated
direct arylation.
Selective reactivity enables the preparation of tailor-made or-
ganic materials and is crucial for obtaining the specific properties
required. For example, 2-aryl-4-bromo-5-methylthiophenes are
key intermediates for electro- and photoactive materials, from
which the bromine can be converted into a plethora of functional
and aromatic groups.7 Furthermore, 2-aryl-4-bromo-5-methylthi-
ophenes are particularly valuable for the preparation of dithieny-
lethene-based photochromic molecules, which can be used for
memory devices, optical switches,8 and biologically relevant
applications9 such as mimicking pyridoxal phosphate,9a regulating
paralysis,9b and Human Carbonic Anhydrase I activity.9c These
properties can be easily tuned according to the aryl group used
in 2-aryl-4-bromo-5-methylthiophenes, and thus a simple and
selective method to prepare these materials is required.
The direct arylation of 3-bromo-2-methylthiophene with vari-
ous aryl bromides was conducted in the presence of pivalic acid,
potassium carbonate, and palladium acetate in dimethylacetamide
according to optimized conditions for product 1, as shown in
Scheme 1. After reacting for 48–60 h at 100 °C, the products were
purified by column chromatography using silica gel. The products
were analyzed by 1H NMR, mass spectrometry, elemental analysis,
and infrared spectroscopy.10 Figure 1 depicts the 1H NMR spectrum
of the starting material compared to representative compounds 3
and 7. In all cases, the two aromatic doublets of 3-bromo-2-meth-
ylthiophene disappeared and the characteristic resonances of 2-
aryl-4-bromo-5-methylthiophene products appeared. Figure
2
shows the mass spectrum of a representative compound 7, which
corresponds to the molecular weight of the target. The pattern
shows two major peaks separated by 2 AMU, which is typical of
monobrominated compounds. IR spectroscopy showed the appear-
ance of functional groups, such as the carbonyl in compound 5, and
the elemental analysis (C, H, S) demonstrated that the products
were pure within 0.4% (see the Supplementary data).
In all cases, the major product was that of the coupling of 3-bro-
mo-2-methylthiophene with the aryl bromide. The yields varied
from 27% to a moderate 63%, and may be improved with optimiza-
tion of each individual reaction. The general trend indicates that
aryl bromides with electron-withdrawing groups, such as acyl (5)
and fluorine (3), resulted in higher yields than that of the
⇑
Corresponding author. Tel.: +61 7 3346 7989; fax: +61 7 3346 9273.
E-mail address: g.vamvounis@uq.edu.au (G. Vamvounis).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.05.015

3786
G. Vamvounis, D. Gendron / Tetrahedron Letters 54 (2013) 3785–3787
Br
Br
+
Ar-Br
Ar
S
S
Ar-Br
Ar-Br
S
Product
Product
Yield
49%
Yield
6
1
56%
Br
Br
H13C6
Br
S
Br
7
8
41%
39%
H13C6
S
2
3
47%
59%
H3C
H7C3
H13C6
2EH
C3H7
C6H13
2EH
Br
F
Br
4
5
27%
63%
9
59%
37%
2EH
O
Br
Br
Br
O
10
Br
S
Scheme 1. Selective direct arylation of 3-bromo-2-methylthiophene. 2EH represents 2-ethylhexyl. Reagents and conditions: pivalic acid, K2CO3, Pd(OAc)2, DMAc, 100 °C, 48–
60 h.
Br
S
Br
S
F
Br
S
H13C6
S
S
Figure 1. 1H NMR (400 MHz) spectra of the 3-bromo-2-methylthiophene starting material and representative compounds 3 and 7 in CDCl3.

G. Vamvounis, D. Gendron / Tetrahedron Letters 54 (2013) 3785–3787
3787
100
75
50
25
0
Acknowledgments
G.V. is the recipient of an ARC Australian Research Fellowship
(DP 1095404). The authors acknowledge support from The Univer-
sity of Queensland (Early Career Researcher Scheme and Strategic
Initiative—Centre for Organic Photonics & Electronics).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
05.015. These data include MOL files and InChiKeys of the most
important compounds described in this article.
420 421 422 423 424 425 426 427 428 429 430
m/z
Figure 2. Mass spectrum of a typical 2-aryl-4-bromo-5-methylthiophene, com-
pound 7.
References and notes
[1]. Guo, Y.; Yu, G.; Liu, Y. Adv. Mater. 2010, 22, 4427.
[2]. Lin, Y.; Li, Y.; Zhan, X. Chem. Soc. Rev. 2012, 41, 4245.
[3]. (a) Thomas, S. W., III; Joly, G. D.; Swager, T. M. Chem. Rev. 2007, 107, 1339; (b)
Toal, S. J.; Trogler, W. C. J. Mater. Chem. 2006, 16, 2871.
[4]. Grimsdale, A. C.; Chan, K. L.; Martin, R. E.; Jokisz, P. G.; Holmes, A. B. Chem.
Rev. 2009, 109, 897.
electron-donating 2-ethylhexyloxy group (4). This general trend
was also observed by Doucet and co-workers 6a The ligands, tricy-
clohexylphosphine (PCy) and tri(o-tolyl)phosphine (TTP) were
used to prepare 1, however the conversion was either similar
(PCy) or lower (TTP) than without the ligand. Importantly, no
homocoupling of 3-bromo-2-methylthiophene was observed. This
suggests that the oxidative addition of the aryl bromide to the
palladium acetate occurs more readily than to 3-bromo-2-methyl-
thiophene. Therefore, this unique selectivity observed is due
to the lower oxidative ability of the bromine in 3-bromo-2-
methylthiophene.
In conclusion, selective direct arylation was demonstrated for
the first time and a library of 2-aryl-4-bromo-5-methylthiophenes
has been prepared. The products were formed in one-step from
commercially available 3-bromo-2-methylthiophene, compared
to the conventional route of brominating 2-methylthiophene, lith-
iation followed by metalation with tributyltin chloride or trimeth-
ylborate, and Stille or Suzuki reaction. These results reveal that the
bromine at the 3-position of the thiophene is not active toward
oxidative insertion of palladium(0) under these conditions giving
a unique opportunity for the facile preparation of tailor-made
functional organic materials.
[5]. (a) Schipper, D. J.; Fagnou, K. Chem. Mater. 2011, 23, 1594; (b) Mercier, L. G.;
LeClerc, M. Acc. Chem. Res. 2013. 10.1021/ar3003305.
[6]. (a) Chen, L.; Roger, J.; Bruneau, C.; Dixneuf, P. H.; Doucet, H. Chem. Commun.
2001, 1872; (b) Steinmetz, M.; Ueda, K.; Grimme, S.; Yamaguchi, J.; Kirchberg,
S.; Itami, K.; Studer, A. Chem. Asian J. 2012, 7, 1256; (c) Fujinami, Y.;
Kuwabara, J.; Lu, W.; Hayashi, H.; Kanbara, T. ACS Macro Lett. 2012, 1, 67; (d)
Berrouard, P.; Najari, A.; Pron, A.; Gendron, D.; Morin, P.-O.; Pouliot, J.-R.;
Veilleux, J.; Leclerc, M. Angew. Chem., Int. Ed. 2012, 51, 2068; (e) Funaki, K.;
Sato, T.; Oi, S. Org. Lett. 2012, 14, 6186; (f) Battace, A.; Lemhadri, M.; Zair, T.;
Doucet, H.; Santelli, M. Adv. Synth. Catal. 2007, 349, 2507.
[7]. Li, Y.; Vamvounis, G.; Yu, J.; Holdcroft, S. Macromolecules 2001, 34, 3130.
[8]. (a) Orgiu, E.; Crivillers, N.; Herder, M.; Grubert, L.; Pätzel, M.; Frisch, J.; Pavlica,
E.; Duong, D. T.; Bratina, G.; Salleo, A.; Koch, N.; Hecht, S.; Samori, P. Nat. Chem.
2012, 4, 675; (b) Myles, A. J.; Branda, N. R. Adv. Funct. Mater. 2002, 12, 167.
[9]. (a) Wilson, D.; Branda, N. R. Angew. Chem., Int. Ed. 2012, 51, 5431; (b) Al-Atar,
U.; Fernandes, R.; Johnsen, B.; Baillie, D.; Branda, N. R. J. Am. Chem. Soc. 2009,
131, 15966; (c) Al-Atar, U.; Lewis, A. R.; Teichman, J. M. H.; Chew, B. H.; Gates,
B. D.; Branda, N. R. Chem. Mater. 2009, 21, 5016; (d) Pace, T. C. S.; Müller, V.; Li,
S.; Lincoln, P.; Andréasson, J. Angew. Chem., Int. Ed. 2013, 52, 4393.
[10]. See the Supplementary data for the detailed synthetic methods and the full
characterization (including spectra) of each compound.