A facile route to thiophene-1,1-dioxides bearing electron-withdrawing groups

Article abstract of DOI:10.1016/S0040-4039(01)00732-8

No commonly available synthetic method for thiophene-1,1-dioxides with strong EWGs has been described to date. Trifluoroperacetic acid in acetonitrile in the absence of water is shown to oxidise thiophenes, including examples possessing an electron-withdrawing group such as sulfonyl or alkoxycarbonyl. An easy and ready for scale-up procedure is developed, some formerly unknown thiophene-1,1-dioxides are obtained.

Full text of DOI:10.1016/S0040-4039(01)00732-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4397–4399
A facile route to thiophene-1,1-dioxides bearing
electron-withdrawing groups
Valentine G. Nenajdenko,* Andrew E. Gavryushin and Elizabeth S. Balenkova
Department of Chemistry, Moscow State University, 119899 Moscow, Russia
Received 8 January 2001; accepted 2 May 2001
Abstract—No commonly available synthetic method for thiophene-1,1-dioxides with strong EWGs has been described to date.
Trifluoroperacetic acid in acetonitrile in the absence of water is shown to oxidise thiophenes, including examples possessing an
electron-withdrawing group such as sulfonyl or alkoxycarbonyl. An easy and ready for scale-up procedure is developed, some
formerly unknown thiophene-1,1-dioxides are obtained. © 2001 Published by Elsevier Science Ltd.
Thiophene-1,1-dioxides serve as intermediates in the
synthesis of numerous classes of organic compounds
via cycloaddition reactions1 or nucleophilic ring-open-
ing.2 Their chemistry has been thoroughly reviewed.3–5
Recently, these compounds have attracted growing
interest as starting materials for the development of
new conducting polymers for optical and electronic
devices.6 Nevertheless, their chemistry is significantly
underdeveloped and their synthetic potential is rela-
tively low due to the lack of general synthetic methods
permitting the preparation of thiophene-1,1-dioxides
with a wide range of substituents.
seemed interesting to investigate the application of this
reagent for the oxidation of thiophenes. The employ-
ment of systems containing trifluoroacetic acid or its
anhydride and aqueous hydrogen peroxide for this pur-
pose was previously reported10–12 and its higher oxida-
tive ability in comparison with the commonly used
mCPBA was demonstrated. However, as was shown for
2-(4-chlorobenzoyl)-thiophenedioxide,11 water easily
adds to the electron-deficient double bonds of such
compounds even in strongly acidic media. Hence, the
absence of water in the oxidizing system is necessary. A
significant merit of this reagent is that all the reaction
products except thiophenedioxides are volatile and can
be easily removed ensuring a convenient workup.
Herein, we report results of our efforts to use trifluoro-
peracetic acid for the oxidation of substituted
thiophenes.
The introduction of an electron-withdrawing group into
a thiophene ring substantially decreases the propensity
of the sulfur atom to undergo oxidation. Although a
number of reagents have been used for the oxidation of
thiophenes, only a few thiophene-1,1-dioxides bearing
an electron withdrawing group are known7,8 and no
representatives with two such substituents are known.
These compounds would be especially interesting as
strained dienes with very low electron density and
presumably high reactivity toward cycloaddition reac-
tions and nucleophilic attack. Hence, the development
of an oxidizing method for EWG-bearing thiophenes
seems to be a worthy task.
Solutions of the reagent were prepared by cautious
addition of trifluoroacetic anhydride to an ice-cold
mixture of the appropriate solvent and 98–99% hydro-
gen peroxide.15 Typically, molar ratios of oxidant–sub-
strate 2.5:1 were used and reactions were carried out at
rt. Preliminary investigation of solvents showed that in
the case of 2,5-dichlorothiophene, a very slow reaction
takes place in chloroform, dichloromethane and
dichloroethane. No reaction occurs in these solvents for
2-chloro-5-methylsulfonyl- and 2-methyl-5-carboethoxy-
thiophenes even after several days at 20°C and the
starting materials were recovered. However, in aceto-
nitrile rapid formation of the oxidized product from
2,5-dichlorothiophene was observed and the reaction
was completed within hours. The isolated product was
identical to the formerly described 2,5-dichlorothio-
phene-1,1-dioxide according to its spectral data and
During our studies of alkenes containing several strong
electron-withdrawing groups, we found trifluoroper-
acetic acid in non-aqueous media to be an excellent
oxidant for electron-deficient sulfur.9 Therefore, it
* Corresponding author. Fax: +7-(095)-932-88-46; e-mail: nen@
acylium.chem.msu.ru
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00732-8

4398
V. G. Nenajdenko et al. / Tetrahedron Letters 42 (2001) 4397–4399
Table 1.
Entry
Thiophene-1,1-dioxide
Yield (%)
7213
Entry
Thiophene-1,1-dioxide
Yield (%)
6613
1
5
2
3
757
828
6
7
767,8
427
4
8514
8
8113
melting point.7 The structures and yields of some thio-
phene-1,1-dioxides obtained by this method are given in
Table 1.
This method permits the preparation of thiophene-1,1-
dioxides containing halogen substituents and/or at least
one strong electron-withdrawing group. The procedure
is extremely simple and can be easily scaled-up. Our
results allow us to hope that the method can be
extended to the oxidation of more electron-deficient
thiophenes. This work is in process in our laboratory
and the results will be reported in due course.
Oxidation of thiophenes containing methylsulfonyl or
carboethoxy groups proceeds much more slowly and
takes up to 2–3 days at rt for completion of the
reaction. Under these conditions we were not able to
oxidize thiophenes with two electron-withdrawing
groups such as 2,5-di-(methylsulfonyl)- or 2,5-dicar-
boethoxythiophene. Increase of the oxidant–substrate
ratio (5:1) gave less satisfactory results in the oxidation
of polyhalogenothiophenes, giving higher amounts of
by-products, though it somehow accelerates the reac-
tion in the cases of carboethoxy- or methylsulfonylthio-
phenes. The double bond in thiophene-1,1-dioxides is
known to be susceptible to epoxidation, and the oxi-
ranes so formed rearrange under acidic conditions into
thiete-1,1-dioxides.5 We presumed these reactions were
occurring in the presence of an excess of trifluoroper-
acetic acid. Also, the reactions run at higher tempera-
tures gave less pure products although in shorter times.
Trifluoroperacetic acid solutions above 35–40°C start to
decompose evolving oxygen, complicating the work at
higher temperatures.
Acknowledgements
The research described in this publication was sup-
ported by the Russian Fundamental Investigation
Foundation (Grant N 00-03-32763a).
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The NMR spectra and melting points for all known
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1: White crystals, mp 147–150°C (dec.). 1H NMR (400
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1
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13. Typical procedure: An equimolar quantity of tri-
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2,5-dibromothiophene was added at 0°C. The mixture
15
.