Catalytic oxidation of thiols to disulfides using iodine and CeCl3·7H2O in graphite

Article abstract of DOI:10.1016/j.tetlet.2007.08.074

A very simple procedure for the efficient oxidation of thiols to disulfides catalyzed by I₂/CeCl₃·7H₂O in graphite and ethyl acetate as the solvent, in an open system at room temperature is described. The reaction proceeds cleanly under mild conditions and was performed with aromatic, aliphatic, and heterocyclic thiols.

Full text of DOI:10.1016/j.tetlet.2007.08.074

Tetrahedron Letters 48 (2007) 7469–7471
Catalytic oxidation of thiols to disulfides using iodine and
CeCl Æ7H O in graphite
3
2
*
Claudio C. Silveira and Samuel R. Mendes
Departamento de Qu ı´ mica, Universidade Federal de Santa Maria, C.P. 5001, 97105-970 Santa Maria, RS, Brazil
Received 2 July 2007; accepted 20 August 2007
Available online 24 August 2007
Abstract—A very simple procedure for the efficient oxidation of thiols to disulfides catalyzed by I /CeCl Æ7H O in graphite and ethyl
2
3
2
acetate as the solvent, in an open system at room temperature is described. The reaction proceeds cleanly under mild conditions and
was performed with aromatic, aliphatic, and heterocyclic thiols.
Ó 2007 Elsevier Ltd. All rights reserved.
The conversion of thiols to the corresponding disulfides
is an important reaction in biological and chemical pro-
cesses. Reagents such as cerium(IV) salts, transition
and 3), while optimal results were achieved using MeCN
and AcOEt (Table 2, entries 1 and 8). Gratifyingly, the
use of AcOEt, an inexpensive and environmentally be-
nign solvent, resulted in the disulfide in quantitative
yield.
1
2
3
4
5
metal oxides, molecular oxygen, nitric oxide, halo-
6
7
8
gens, sodium perborate, H O , solvent free perman-
2
2
9
10
ganate, 2,6-dicarboxypyridinium chlorochromate,
1
,3-dibromo-5,5-dimethylhydantoin,11 among others
Our next attention was devoted to minimum amounts of
1
2
have been utilized for oxidation of thiols to disulfides.
iodine and CeCl to have a good reaction rate. We ob-
3
served that the amounts of both reagents can be reduced
substantially, to 5 and 10 mol % (Table 2, entry 8),
respectively. It is worthy to note the effect of iodine
In the course of studies on some reaction of CeCl Æ7H O
and iodine, we have observed the oxidative dimerization
3
2
of thiols. Our continuing interest in the synthesis and
applications of organochalcogenium chemistry
and CeCl on the oxidation. Under the standard condi-
3
1
3
tions, the absence of iodine or CeCl reduces the conver-
3
prompted us to examine and expand the scope of this
reaction. A set of experiments were performed to find
the best conditions for the oxidation, using thiophenol
as a model compound. A series of different supports
and solvents were examined and results are presented
in Tables 1 and 2, respectively. By the results described
in Table 1, one can observe that the use of graphite is a
very convenient solid support for the reaction, per-
formed without any solvent. Graphite has been emerg-
ing as a very convenient support for a series of
synthetic transformations. However, as the reaction
under dry media condition was not efficient, with 83%
conversion (GC analysis) in graphite after 9 h, we turned
our attention to the use of a solvent. We observed mod-
erate yields using EtOH and MeOH (Table 2, entries 2
sion rates substantially (Table 2, entries 6 and 7).
Careful analysis revealed that the optimum conditions
for this oxidation reaction were found to be the use of
ethyl acetate and graphite, under catalysis of CeCl3Æ
7H O (10 mol %) and I (5 mol %), at room temperature
2
2
and air atmosphere (Scheme 1). A detailed study was
performed with aliphatic, aromatic, and heterocyclic
thiols, showing the generality of the method. For most
examples, very high yields were obtained, the exceptions
1
4
Table 1. Oxidation of thiophenol in dry media at different supports
a
Entry
Support
Time (h)
Conversion (%, GC)
1
2
3
4
—
SiO
PEG400
Graphite
9
9
9
9
11
27
17
83
2
Keywords: Thiols; Disulfides; Oxidation; Cerium chloride; Iodine;
Graphite.
a
*
Corresponding author. Tel./fax: +55 55 32208754; e-mail:
silveira@quimica.ufsm.br
PhSH (1 mmol), support (0.3 g), I
1 mmol).
2 3 2
(1 mmol) and CeCl Æ7H O
(
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.08.074

7470
C. C. Silveira, S. R. Mendes / Tetrahedron Letters 48 (2007) 7469–7471
Table 2. Oxidative coupling of thiophenol supported in graphite under
different solvent
Acknowledgments
a
Entry Solvent
Time
I
2
CeCl
3
Æ7H
2
O
Conversion
(%, GC)
The authors thank FAPERGS, MCT/CNPq and
CAPES for financial support.
(
h)
(equiv) (equiv)
1
2
3
4
5
6
7
8
9
MeCN
MeOH
EtOH
AcOEt
AcOEt
AcOEt
AcOEt
AcOEt
AcOEt
1
1
1
1
1
0.08
—
0.08
0.05
0.05
1
1
1
1
0.5
0.5
—
0.1
0.1
100
57
44
100
100
39
14
14
1
1
1
1
1
14
References and notes
1
2
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Group, Part 2; Patai, S., Ed.; Wiley: New York, 1974; (b)
Jocelyn, D. C. Biochemistry of the Thiol Group; Academic
Press: New York, 1992.
. (a) Dhar, D. N.; Bag, A. K. Indian J. Chem. 1984, 23B,
974; (b) Firouzbadi, H.; Iranpoor, N.; Parham, H. A.
Synth. Commun. 1984, 14, 717.
75
100
b
33
a
Solvent (1 mL/mmol), PhSH (1 mmol), graphite (0.3 g/mmol).
Reaction performed without graphite.
b
3
4
5
. Wallace, T. J. J. Org. Chem. 1966, 31, 1217.
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J. Org. Chem. 1982, 47, 156.
I2 (5 mol%),CeCl ·7H O (10 mol%)
3
2
R
SH
R
S
S R
AcOEt / Graphite
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1
a-h
2 a-h
Scheme 1.
being entries 7 and 8, Table 3, mostly related to difficulty
of isolation of the corresponding disulfide, since the
reactions demanded the use of water as a co-solvent
and adjust of pH. The oxidation reaction can be easily
scaled-up with similar results.
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1
5
1
990, 55, 2337.
9
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1
1
0. Tajbakhsh, M.; Hosseinzadeh, R.; Shakoori, A. Tetrahe-
dron Lett. 2004, 45, 1889.
1. Khazaei, A.; Zolfigol, M. A.; Rostami, A. Synthesis 2004,
In conclusion, the method described is very simple and
efficient for coupling of thiols, using catalytic amounts
of iodine and CeCl3 in the inexpensive graphite as
solid support. The method is applicable to a wide variety
of thiols, being a useful alternative of the existing
methodologies.
2
959.
12. (a) Akdag, A.; Webb, T.; Worley, S. D. Tetrahedron Lett.
006, 47, 3509; (b) Hajipour, A. R.; Mallakpour, S. E.;
2
Adibi, H. J. Org. Chem. 2002, 67, 8666; (c) Shaabani, A.;
Teimouri, F.; Lee, D. G. Synth. Commun. 2003, 33, 1057;
Table 3. Catalytic oxidation of thiols to disulfides
a
Entry
1
Thiol
Time (h)
1.5
Product
Yield (%)
Mp/bp °C (Lit.)
b
16
2a
97
195 (194/760 mmHg)
SH
SH
SH
b
17
2
3
4
5
0.8
1.0
1.0
0.9
2b
98
99
97
98
30–32 (32)
1
0
b
18
2c
57–58 (59–60)
SH
b
6b
2d
69–70 (70–71)
b
19
MeO
Cl
SH
2e
42–43 (43–44)
b
20
6
7
SH
1.0
2.5
2f
96
74
72–73 (73–74)
N
c
21
SH
2g
167–169 (168–170)
N
O
OH
SH
c
22
8
3.5
2h
77
243–245 dec (>240 dec)
2
H N
a
b
c
Isolated yield.
Reaction in AcOEt (Method A).
Reaction in AcOEt/H O (Method B).
2

C. C. Silveira, S. R. Mendes / Tetrahedron Letters 48 (2007) 7469–7471
7471
(
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2
S
2
O
3
, water, and dried over
3
1, 3591.
MgSO . The solvent was removed and the residue purified
4
1
1
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by recrystallization or silica gel chromatography. Method
B: Ethyl acetate (1 mL) was added to a solution of thiol
(1 mmol) in water (1 mL) and the pH was adjusted to 10
3
701.
with 1 M aq NaOH. Then graphite (0.3 g), I
2
(0.05 mmol),
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3
2
was monitored by TLC or GC until completion, and the
reaction mixture was evaporated to dryness. Product 2g
was extracted and purified as described in Method A.
Product 2h was recrystalized from water.
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1
5. General procedures for the oxidation. Method A: A round
bottom flask was charged with ethyl acetate (1 mL),
19. Iranpour, N.; Zeynizadeh, B. Synthesis 1999, 49.
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838.
graphite (0.3 g),
I
2
3 2
(0.05 mmol), and CeCl Æ7H O
(
0.1 mmol). The mixture was stirred for 10 min, then the
thiol (1 mmol) was added. The reaction was monitored by
TLC or GC. After completion of the reaction, ethyl
acetate (25 mL) was added and the reaction mixture was
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22. From commercial available compound.