A mild and efficient protocol for oxidation of thiols to disulfides in water

Article abstract of DOI:10.1002/hc.20760

A novel vanadium polyoxometalate [(C₇H₇)(CH ₃)₃N]₃[H₃V₁₀O ₂₈].3H₂O works as a useful oxidant for the oxidation of thiols to disulfldes in water under mild reaction conditions in an excellent yield.

Full text of DOI:10.1002/hc.20760

Heteroatom Chemistry
Volume 23, Number 2, 2012
A
Mild and Efficient Protocol for Oxidation
of Thiols to Disulfides in Water
1
2
1
Anindita Dewan, Utpal Bora, and Dilip K. Kakati
1
Department of Chemistry, Gauhati University, Guwahati 781 014, India
2
Department of Chemistry, Dibrugarh University, Dibrugarh 786 004, India
Received 13 May 2011; revised 31 July 2011
view, the use of water as a solvent in organic reac-
tions has attracted tremendous interest because wa-
ter is very cheap, readily available, and nontoxic [15].
Therefore, synthetic organic reactions in water at an
ambient temperature have attracted widespread in-
terest. Among the various transition metals, vana-
dium exists on the surface of the earth more abun-
dantly and vanadium-based oxidants are effectively
used for the oxidation of thiols to disulfides [16].
Very recently, we reported on the synthesis and
crystal structure of a novel vanadium polyoxomet-
ABSTRACT: A novel vanadium polyoxometalate
[
(C
7
H
7
)(CH
3
)
3
N]
3
[H
3
V
10
O28].3H O works as a useful
2
oxidant for the oxidation of thiols to disulfldes in
water under mild reaction conditions in an excellent
yield. ꢀC 2011 Wiley Periodicals, Inc. Heteroatom Chem
2
3:231–234, 2012; View this article online at wileyonlineli-
brary.com. DOI 10.1002/hc.20760
INTRODUCTION
alate [(C
treating V
7
H
2
7
)(CH
3
)
3
N]
3
[H
3
V
10
O
28]·3H
2
O obtained by
The oxidation of thiols to disulfides without forma-
tion of an overoxidized product is one of the most
pivotal transformations in chemical and biochemi-
cal processes [1]. Several methods involving bromine
O
5
with H
2
O in the presence of ben-
2
zyltrimethylammonium chloride and their applica-
tion in oxidation reactions [17]. Polyoxometalates
are considered to be a unique catalytic species be-
cause of their multifunctionality and structural mo-
bility [18]. The objective of the present study is to
establish the viability of the newly synthesized vana-
dium polyoxometalates in the oxidation of thiols to
disulfides under mild reaction conditions.
[2], KMnO
4
/CuSO [3], manganese(III) Schiff-base
4
complex [4], potassium dichromate [5], rhodium
complex [6], iron metal–organic frameworks [7],
aluminium nitrate [8], I
Ni-nanoparticles [10], NaI/H
2
/CeCl
3
·7H
2
O in graphite [9],
[11], and cobalt(III)
2
O
2
ions [12] have been explored on disulfide forma-
tion. Recently, green reaction methodologies such as
sonication [13] and microwave heating under
solvent-free conditions [14] are also being applied to
synthesize disulfides. However, the main drawbacks
associated with these systems are the use of expen-
sive and harmful metals and toxic organic solvents,
a long reaction time, and in the majority of cases,
the requirement of an elevated temperature for ef-
fective catalytic activity. It is noteworthy to mention
that from an environmental and economic point of
RESULTS AND DISCUSSION
To investigate the effectiveness of the vanadium
polyoxometalate complex in the oxidation reac-
tion, thiophenol was chosen as a model substrate.
Initially, we carried out the oxidation reaction by
treating thiophenol (1 mmol) with vanadium poly-
oxometalate (0.05 mmol) in water (5 mL) under
neutral and aerobic conditions. Table 1 shows that
the reaction proceeded with a 40% yield within
a minute (entry 1) accompanied by a significant
amount of an unidentified side product. The yel-
low color of the reaction mixture instantaneously
Correspondence to: Utpal Bora; e-mail: utbora@yahoo.co.in.
ꢀ
c 2011 Wiley Periodicals, Inc.
231

232 Dewan, Bora, and Kakati
TABLE 1 Optimization of Reaction Conditions for V-Polyoxometalate–Mediated Oxidation of Thiolsa
Oxidant
SH
S
Solvent/Additive
S
◦
Entry
Oxidant
Oxidant (mmol)
Solvent/Additive
T ( C)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
V-polyoxometalate
V-polyoxometalate
V-polyoxometalate
V-polyoxometalate
V-polyoxometalate
V-polyoxometalate
V-polyoxometalate
V-polyoxometalate
V-polyoxometalate
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
–
0.10
0.001
0.005
0.01
0.03
Water
Water
Water
rt
60
5
5
5
5
5
5
5
5
5
5
5
5
5
1
1
1
30
1
1
1
1
30
5
1
40
45
55
58
60
63
64
92
90
5
88
25
30
70
85
Water
Water/methanol
Water/THF
Water/CH CN
3
Water/SDS
Water/SDS
Water/SDS
Water/SDS
Water/SDS
Water/SDS
Water/SDS
Water/SDS
10
11
12
13
14
15
V O5/H O /BTAC
2
2
2
V-polyoxometalate
V-polyoxometalate
V-polyoxometalate
V-polyoxometalate
V-polyoxometalate
1
1
1
1
aReaction conditions: Thiophenol (1.0 mmol); sodium dodecyl sulfate (SDS; 0.1 mmol). All yields refer to isolated yields.
became blue upon stirring, indicating the progress
of the reaction. An increase in reaction temper-
ature to 60 C could neither improve the yield of
(Table 1, entry 9). However, the yield of the prod-
uct was dramatically decreased when the oxidant
◦
was replaced by V
2
O
5
, H
2
2
O , and benzyltrimethy-
the product nor suppress the formation of the
side product (Table 1, entry 2). But a decrease in
the reaction temperature to 5 C (bath temperature)
lammonium chloride (BTAC) under the same re-
action conditions (Table 1, entry 10). Several test
reactions were carried out using different amounts
of V-polyoxomatalate to find the optimal amount of
catalyst required for this transformation. It was ob-
served that 0.05 mmol of V-polyoxometalate is suf-
ficient for the smooth oxidation of 1.0 mmol of the
substrate (Table 1, entries 11–15).
To evaluate the scope and limitations of the
current procedure, oxidation reactions with a wide
array of electronically diverse thiols were ex-
amined using V-polyoxometalate. The results are
summarized in Table 2. The table shows that,
in general, various phenyl ring substituted thiols
underwent the oxidation reactions with excellent
yields. The electronic properties and position of the
substituents had less of an effect on the reaction
process. Both electron-withdrawing and electron-
donating substituents, such as o-Cl, p-Cl, m-Cl, o-
◦
gave the desired product with an improved yield
(Table 1, entry 3). However, an increase in the reac-
tion time to 30 min did not have any impact on the
product yield (Table 1, entry 4). The insolubility in
water of most of the reagents and substrates restricts
their use in water as a solvent. Therefore, we car-
ried out the reaction in 50% aqueous methanol and
the yield of disulfide was slightly increased under
the reaction conditions (Table 1, entry 5). Similarly,
5
0% aqueous tetrahydrofuran (THF) and acetoni-
trile gave almost comparable results (Table 1, entries
and 7) under the same reaction conditions. Thus,
6
we decided to use sodium dodecyl sulfate (SDS) as
an additive because SDS was previously used on a
number of occasions to improve the yield in water
[19].
Interestingly, the use of SDS as an additive
OMe p-OMe, p-OH, o-NH
2
, p-NH , o-Me, p-Me, and
2
in the water was found to be very effective and
gave desired disulfides in an excellent yield. In
this particular case, the thiophenol was converted
to its disulfide derivative in a very high yield
within a minute, upon just stirring the thiophe-
p-NO in the benzene ring, gave the desired products
2
with a 75%–92% yield (Table 2, entries 1–12). How-
ever, a slightly extended reaction time was required
for the sterically demanding ortho-substituted thiols
(Table 2, entries 4, 8, 10, and 12) to give the de-
sired product in a good yield. The reaction is also
compatible with heteroaromatic (Table 2, entry 13)
and aliphatic thiols (Table 2, entries 14 and 15). No
◦
nol and oxidant in the presence of SDS at 5 C
(Table 1, entry 8). An increase in reaction time
to 30 min did not improve the yield of disulfide
Heteroatom Chemistry DOI 10.1002/hc

A Mild and Efficient Protocol for Oxidation of Thiols to Disulfides in Water 233
TABLE 2 Oxidation of Different Thiols to Disulfidesa
taneously upon stirring, indicating the progress
of the reaction. After completion of the reaction,
the reaction mixture was diluted with ethylacetate
V-polyoxometalate
S
R
R
S
R
S
(20 mL) and washed with water (3 × 10 mL). The
o
Water, SDS, 5 C
organic layer was washed with brine (3 × 20 mL),
dried over anhydrous Na
2
SO , concentrated, and
4
Entry
Substrate (R)
Time (min)
Yield (%)
finally purified by passing through a short column
of silica gel (60–120 mesh) to obtain disulfide as
1
2
3
4
5
6
7
8
9
C H5
6
1
1
1
3
1
1
1
3
2
3
1
3
2
1
1
92
85
80
76
85
90
90
75
88
78
87
80
85
75
70
4-Cl-C H5
◦
6
a white solid with a 92% yield. mp 57–59 C (lit.
3-Cl-C H5
◦
1
6
[
16c] mp: 58–60 C). H NMR (CDCl
δ: 7.50–7.44 (m, 4H), 7.29–7.16 (m, 6H). C NMR
CDCl , 75.5 MHz) δ: 135.0, 125.9, 124.2, 129.3.
3
, 300 MHz)
2-Cl-C H5
6
13
4-OH-C H5
6
(
3
4-NO -C H5
2
6
4-OMe-C H5
2-OMe-C H5
MS(ESI): 219 (M + 1).
6
6
4-NH -C H5
2
6
10
11
12
13
14
15
2-NH -C H5
2 6
4-CH -C H5
CONCLUSIONS
3
6
2-CH -C H5
3
6
2-Pyridyl
In conclusion, we developed an efficient method for
the oxidation of thiols to the corresponding disul-
fides under mild and neutral reaction conditions in
an aqueous medium. The synthesis of this oxidant
is very simple, and starting materials used are com-
mercially available and cheap. The oxidant is also
very stable and hence can be stored and handled
very easily. The reaction time is very short, and no
overoxidized product was observed.
OH-CH CH2
2
CH CHCH3
3
aReaction conditions: Thiol (1.0 mmol), V-polyoxometalate (0.05
mmol), sodium dodecyl sulfate (SDS; 0.1 mmol), water (5 mL); stirred
◦
at 5 C(bath temperature). All yields refer to isolated yields. The struc-
1
tures of compounds were determined by using H NMR, FTIR, and
mass spectra and compared with authentic samples.
overoxidized product was observed in any of the thi-
ols studied. Although not confirmed, it was believed
that in the presence of the polyoxometalate complex,
the reaction probably proceeded via a free radical
pathway. The dissolved oxygen in water allows the
formation of thiyl radicals, which have been pro-
posed earlier as intermediates in disulfide formation
REFERENCES
[1] (a) Capozzi, G.; Modena, G. In The Chem-
istry of the Thiol Group; Patai, S. (Ed.); Wiley:
London, 1974; Part 2, Ch. 17, p. 801 and refer-
ences cited therein; (b) Joceyln, P. C. Biochemistry
of the Thiol Group; American Press: New York,
1992.
[20]. The presence of the V-polyoxometalate com-
plex as an oxidant facilitates the progress of disulfide
formation under our reaction conditions. We also ex-
amined the reusability of V-polyoxometalate using
thiphenol as a substrate. The reaction was carried
out successfully until the third run without either a
significant loss of yield or an extension of reaction
time; yields of 88% (cycle-1), 85% (cycle-2), and 82%
[2] Wu, X.; Reike, R. D.; Zhu, L. Synth Commun 1996,
2
6, 191–196.
[
[
3] Noureldin, N. A.; Caldwell, M.; Hendry, J.; Lee, D. G.
Synthesis 1998, 1587–1589.
4] Golchoubian, H.; Hosseinpoor, F. Catal Commun
2007, 8, 697–700.
[5] Patel, S.; Mishra, B. K. Tetrahedron Lett 2004, 45,
371–1372.
1
(cycle-3) in the aqueous phase were recovered from
[
[
[
6] Arisawa, M.; Sugata C.; Yamaguchi, M. Tetrahedron
Lett 2005, 46, 6097–6099.
7] Dhakshinamoorthy, A.; Alvaro, M.; Hermenegildo, G.
Chem Commun 2010, 46, 6476–6478.
8] Ghorbani-Choghamarani, A.; Nikoorazm, M.;
Goudarziafshar, H.; Tahmasbi, B. Bull Korean Chem
Soc 2009, 30, 1388–1390.
an ethyl acetate extract.
EXPERIMENTAL
General Procedure for Oxidation of Thiophenol
[
9] Silverira, C. C.; Mendes, S. R. Tetrahedron Lett 2007,
A 50-mL round-bottom flask was charged with a
mixture of thiophenol (0.122 g, 1.0 mmol), vanadium
4
8, 7469–7471.
[10] Saxena, A.; Kumar, A.; Mozumdar, S. J Mol Catal A:
Chem 2007, 269, 35–40.
polyoxometalates [C
7
H
7
N(CH
3
)
3
]
3
V
10
O
28
H
3
·3H
2
O]
[
11] Kirihara, M.; Asai, Y.; Ogawa, S. Noguchi, T.;.
Hatano, A.; Hirai, Y. Synthesis 2007, 3286–3289.
12] Hill, J.; McAuley, A. J Chem Soc A 1968, 2405–2408.
13] Ruano, J. L. G.; Parra, A.; Aleman, J. Green Chem
2008, 10, 706–711.
(0.073 g, 0.05 mmol), and SDS (0.288 g, 0.1 mmol),
and the mixture was stirred in H
2
O (5 mL) at
[
[
◦
5
C (bath temperature) for the required time. The
yellow color of the mixture changed to blue instan-
Heteroatom Chemistry DOI 10.1002/hc

234 Dewan, Bora, and Kakati
[
[
[
14] Lenardao, E. J.; Lara, R. G.; Silva, M. S.; Jacob,
R. G.; Perin, G. Tetrahedron Lett 2007, 48, 7668–
Lett 2011, 55, 2563–2565; (c) Dewan, A.; Bora, U.;
Kakati, D. K. Bull Korean Chem Soc 2011, 31,
2482.
7
670.
15] (a) Lindstrom, U. M. Chem Rev 2002, 102, 2751–2772;
b) Herrerias, C. I.; Yao, C. X.; Li, Z.; Li, C. J. Chem
[18] (a) Maeda, Y.; Kakiuchi, N.; Mastsumura, S.;
Nishimura, T.; Uemura, S. Tetrahedron Lett 2001,
42, 8877–8879; (b) Kodama, S.; Ueta, Y.; Yoshida,
J.; Nomoto, A.; Yano, S.; Ueshima, M.; Ogawa, A.
Dalton Trans 2009, 9708–9711; (c) Radosevich, A. T.;
Musich, C; Toste, F. D. J Am Chem Soc 2005, 127,
1090–1091.
(
Rev 2007, 107, 2546–2562.
16] (a) Raghavan, S.; Rajender, A.; Joseph, S. C.;
Rasheed, M. A. Synth Commun 2011, 31, 1477–1480;
(
1
b) Pickering W. F.; McAuley, A. J Chem Soc 1968,
173–1176; (c) Kirihara, M.; Okubo, K.; Uchiyama,
T.; Kato, Y.; Ochiai, Y.; Matsushita, S.;. Hatano,
A; Kanamori, K. Chem Pharm Bull 2004, 52, 625–
[19] Gogoi, P.; Hazarika, P.; Konwar, D. J Org Chem 2005,
70, 1934–1936.
[20] (a) Carril, M.; SanMartin, R.; Dominguez, E.; Tellitu,
I. Green Chem 2007, 9, 315–316; (b) Wallace, T. J.;
Schriesheim, A.; Bartok, W. J Org Chem 1963, 28,
1311–1314.
6
27.
[
17] (a) Dewan, A.; Kakati, D. K.; Das, B. K. In-
dian J Chem A 2010, 49, 39–44; (b) Dewan, A.;
Sarma, T.; Bora, U.; Kakati, D. K. Tetrahedron
Heteroatom Chemistry DOI 10.1002/hc