Base-free oxidation of thiols to disulfides using selenium ionic liquid

Article abstract of DOI:10.1016/j.tetlet.2010.11.158

We present here the results on the use of 1-n-butyl-3-methylimidazolium methylselenite, [bmim][SeO₂(OCH₃)], in the synthesis of symmetrical disulfides starting from thiols. This efficient and improved method is general for aromatic, aliphatic, and functionalized thiols affording the disulfides in good to excellent yields after easy work up. The use of a microwave accelerates the reaction and the [bmim][SeO₂(OCH ₃)] was reused for further oxidation reactions.

Full text of DOI:10.1016/j.tetlet.2010.11.158

Tetrahedron Letters 52 (2011) 640–643
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Base-free oxidation of thiols to disulfides using selenium ionic liquid
Samuel Thurow, Vanda A. Pereira, Débora M. Martinez, Diego Alves, Gelson Perin, Raquel G. Jacob,
⇑
Eder J. Lenardão
Instituto de Química e Geociências, LASOL, Universidade Federal de Pelotas, UFPel, PO Box 354, 96010-900 Pelotas, RS, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
We present here the results on the use of 1-n-butyl-3-methylimidazolium methylselenite, [bmim]
Received 29 October 2010
Revised 27 November 2010
Accepted 30 November 2010
Available online 5 December 2010
[
2 3
SeO (OCH )], in the synthesis of symmetrical disulfides starting from thiols. This efficient and improved
method is general for aromatic, aliphatic, and functionalized thiols affording the disulfides in good to
excellent yields after easy work up. The use of a microwave accelerates the reaction and the [bmim]
2 3
[SeO (OCH )] was reused for further oxidation reactions.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Selenium ionic liquid
Disulfides
Oxidation
1
Thiols and disulfides are important in both biological and
2
[bmim][SeO
(OCH )]
2 3
chemical processes. Disulfides are useful reagents in organic syn-
2
RSH
RS SR
2
thesis and essential moieties of biologically active compounds for
60 ºC or MW at 30 ºC, air
1
peptide and protein stabilization. As disulfides are relatively more
R = Ar, HetAr, Alkyl
stable toward organic reactions, such as oxidation, alkylation, and
acylation, compared to the corresponding free thiols, the thiol
group can conveniently be protected as a disulfide. Besides, there
are a large number of commercially available thiols and the inter-
conversion between thiols and disulfides is easy.3 These aspects
are responsible for the continuous interest in the development of
new, selective, and efficient protocols for the preparation of disul-
Scheme 1. General scheme of reaction.
and/or selectivity improvements are also observed, they are re-
garded as environmentally friendly green solvents. In this context,
7
4
the use of [bmim][BF ] as a solvent for the oxidation of thiols in the
8
2
,4,5
presence of a base was described. Recently, we have reported the
use of the new cationic selenium-based acidic ionic liquid phenyl
fides.
Recently reported procedures to obtain symmetrical
4
a
disulfides involve the use of anhydrous potassium phosphate,
4b
4
butyl ethyl selenonium tetrafluoroborate, [pbeSe][BF ], as an effi-
cient catalyst in several acid-catalyzed reactions. Besides, the
application of the ionic liquid containing anionic selenium-based
potassium permanganate, molecular bromine supported on silica
9
4
c
4d
4e
gel, N-phenyltriazolinedione, VO(acac)
2
,
trichloroisocyanuric
4
f
4g
4h
acid, nitric acid, 1,3-dibromo-5,5-dimethylhydantoin, basic
4
i
4j
4k
[
2 3
bmim][SeO (OCH )] in the oxidative carbonylation of aniline
alumina, CsF–Celite, and montmorillonite K10. Additionally,
cleaner protocols under solvent-free conditions were described.
These methods use N-phenyltriazolinedione, pyridinium chloro-
chromate, 1,3-dibromo-5,5-dimethylhydantoin, SO
1
0
4
d,6
was also described. The selenium-containing ionic-liquids shown
superior catalytic performance and were reused without losing
4d
1
0
6
a
6b
6c
their initial activity. Due to our interest in new applications for
2
Cl
supported on
Á7H
as catalysts. Thus, there is still an
2
,
tri-
9
6
d
6
6e
selenium-based ionic liquids, we decide to study the use of
chloronitromethane,
KMnO
4
/MnO
2
,
KMnO
4
1
0
f
[
2 3
bmim][SeO (OCH )] as the solvent in the oxidation of thiols to
montmorillonite K10, catalytic amount of iodine, and CeCl
in graphite, and KF/Al O
2 3
3
2
O
6
g
6h
symmetrical disulfides (Scheme 1).
Initially, we chose benzenethiol as a substrate to establish the
best condition for the air oxidation reaction in the presence of
attention in developing green methods that would produce the
desirable disulfides in high yields.
In this way, ionic liquids (ILs) constitute an interesting alterna-
tive for this reaction. Because product isolation or catalyst recy-
cling is very easy in ILs and, in some cases, rate accelerations
1
.0 mL of [bmim][SeO
2
(OCH
3
)]. Thus, a mixture of benzenethiol
(OCH )] was stirred for 12 h at room
(
1.0 mmol) and [bmim][SeO
2
3
temperature furnishing diphenyl disulfide 1a in 45% yield. This
unexpected, new result showing the ionic liquid acting both, as a
solvent and catalyst, encouraged us to investigative the effect of
the temperature in this base-free oxidation. To our satisfaction,
⇑
Corresponding author. Tel./fax: +55 5332757533.
E-mail address: lenardao@ufpel.edu.br (E.J. Lenardão).
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.11.158

S. Thurow et al. / Tetrahedron Letters 52 (2011) 640–643
641
Table 1 (continued)
SH [bmim][SeO (OCH )]
2
3
S
S
2
0 oC, air
Product yield [lit.]
6
Entry
Time (h)
1a
Cl
NH2
S
S
9
14
NH2
Cl
1
8%
i
[19]
7
S
S
1
1
1
0
5
2
4
Figure 1. Plot of conversion versus time for the oxidation of benzenethiol
determined by GC).
1j
[20]
(
88%
S
Table 1
N
S
S
S
2 3
Synthesis of disulfides 1a–r using [bmim]SeO (OCH
)] according method Aa
1b
N
Product yield [lit.]
Entry
Time (h)
1
9%
k
[21]
9
S
S
S
1
3
S
2
3
1
8%
a
[12]
9
1l
[14]
9
8%
Cl
S
S
2
3
2
4
S
S
1
4
1
9%
b
[13]
9
9
Cl
1
7%
m
[22]
8
S
S
S
S
n
1
1
4
5
3
4
1
9%
[23]
9
1
9%
c
[14]
S
S
11
11
MeO
1
84%
o
[24]
S
S
4
3
S
OMe
S
1
9%
d
16
4
[
15]
9
1p
[18]
8
0%
Cl
HO
HO
S
S
S
OH
S
S
1
1
7
8
18
1q
85%
5
6
4
4
[25]
Cl
1
8%
e
[14]
NH2
O
9
S
OH
8
O
NH
2
S
Cl
Cl
Cl
S
1r[20]
8
7%
1
f
a
Yields are given for pure isolated products.
Reaction was performed at 100 °C.
[
16]
9
3%
b
S
at a gentle heating (60 °C), the reaction proceeded slowly furnish-
ing the desired diphenyl disulfide 1a in 98% isolated yield after
S
7b
3
3
Cl
Br
1
2 h. In order to obtain an efficient protocol in terms of energy
1
9%
g
[17]
economy, we make a study to establish the minimum time associ-
ated with a good reaction rate under the optimized conditions, and
the results are summarized in Figure 1.
9
Br
S
Analyzing the Figure 1, total conversion of benzenethiol was ob-
served after 3 h of reaction. A further decreasing of the reaction
time was followed by a considerable reduction in the conversion
rate of benzenethiol.
S
8b
1
h
[18]
9
9%
Under the optimized conditions (method A),11 a variety of orga-
nothiols were oxidized smoothly to produce disulfides 1a–r in

6
42
S. Thurow et al. / Tetrahedron Letters 52 (2011) 640–643
Table 2
a
SH [bmim][SeO (OCH )]
Synthesis of disulfides according method B
2
3
S
2
S
MW, 30 ºC, air
Entry
Time (min)
Product yield
1a
98
98
96
96
94
S
S
1
00
1
15
8
0
0
0
1
a
6
4
9
8%
MeO
S
20
0
S
2
3
20
15
OMe
1
2
3
4
5
1
d
Runs
9
8%
Cl
2 3
Figure 2. Reuse of [bmim][SeO (OCH )] under microwave irradiation.
S
S
orated. The inferior, ionic liquid phase was dried under vacuum
and reused. The selenium ionic liquid maintained its good level
of oxidation activity even after being recycled four times as shown
in Figure 2. The product 1a was obtained in 98%, 98%, 96%, 96%, and
Cl
1
9
g
9%
9
4% yields after successive cycles.
3
In conclusion, [bmim][SeO (OCH )] has proved to be an efficient
S
S
4
5
6
30
20
15
2
medium for the oxidation of aromatic, aliphatic, and functionalized
thiols. The Se-ionic liquid acts both as solvent and catalyst and is
easily recovered and utilized for further oxidation reactions. The
reactions are accelerated by microwaves and the desired disulfides
were obtained in good to excellent yields.
1
1%
j
9
S
N
S
S
N
S
1
l
Acknowledgments
9
7%
We are grateful to FAPERGS (FAPERGS/PRONEX 10/0005-1 and
S
1
0/0027-4), CAPES, FINEP and CNPq for the financial support.
S
References and notes
1
m
9
5%
1
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a
Yields are given for pure isolated products.
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Diaryl disulfides containing electron donating (Table 1, entries
2
–4) and electron withdrawing groups (Table 1, entries 5–8), could
be obtained in high yields. Good yields of oxidation were obtained
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2.
3
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4
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(
2
8
7% yield (Table 1, entry 18).
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Thus, the mixture of benzenethiol (1.0 mmol) and [bmim][-
(OCH )] was irradiated under stirring and fortunately, after
2 3
5 min at 30 °C, diphenyl disulfide 1a was obtained in 98% (meth-
od B). To extend the scope of method B, other organothiols were
irradiated with microwaves and the corresponding disulfides
shown in Table 2 were obtained in excellent yields.
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1
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washings with petroleum ether (3 Â 5 mL), dried over MgSO
4
, and
concentrated in vacuum. The residue was purified by column
chromatography on silica gel using ethyl acetate/hexanes as the eluent.
Recycle of the ionic liquid: The aforementioned method B was used with
benzenethiol (0.110 g, 1.0 mmol) and the inferior ionic liquid phase was
8
.
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separated and dried under vacuum. The recovered [bmim][SeO
used directly in the next cycle.
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2 3
(OCH )] was
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1
0. For the synthesis of [bmim][SeO
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1. General procedure for the oxidation of thiols with [bmim][SeO (OCH )]: Method A:
In a Schlenk tube under open atmosphere and at room temperature, the
2 3
(OCH )] see: Kim, H. S.; Kim, Y. J.; Lee, H.;
1
2
3
10
corresponding thiol (1.0 mmol) was added to [bmim][SeO
The reaction mixture was allowed to stir at 60 °C for the time indicated in Table
. The progress of the reaction was monitored by TLC. Method B: In a 10 mL
glass vial equipped with a small magnetic stirring bar, containing 1.0 mL of
bmim][SeO (OCH )] was added the thiol (1.0 mmol). The vial was tightly
2
(OCH
3
)] (1.0 mL).
1
[
2
3
sealed with an aluminum/Teflon crimp top. The mixture was then irradiated in
a microwave reactor (CEM Explorer) for the time indicated in Table 2 at 30 °C
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(
temperature was measured with an IR sensor on the outer surface of the