A facile oxidation of thiols to disulfides catalyzed by CoSalen

Article abstract of DOI:10.1080/10426507.2011.568025

A convenient and facile catalytic oxidation of thiols to the corresponding disulfides is described using CoSalen as the catalyst and air as the oxidizing agent. This new approach provides an efficient method for the preparation of symmetrical disulfides in high yields and under mild conditions. [Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Spectroscopic Identification of Products 3a-3l.] Copyright Taylor and Francis Group, LLC.

Full text of DOI:10.1080/10426507.2011.568025

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A Facile Oxidation of Thiols to Disulfides
Catalyzed by CoSalen
Cheng-Xia Tan a , Li-Yan Pan a , Guo-Fu Zhang a & Yong-Shu Li b
a College of Chemical Engineering and Materials Sciences, Zhejiang
University of Technology, Hangzhou, P. R. China
b College of Pharmaceutical Sciences, Zhejiang University of
Technology, Hangzhou, P. R. China
Published online: 06 Dec 2011.
To cite this article: Cheng-Xia Tan , Li-Yan Pan , Guo-Fu Zhang & Yong-Shu Li (2012) A Facile
Oxidation of Thiols to Disulfides Catalyzed by CoSalen, Phosphorus, Sulfur, and Silicon and the Related
Elements, 187:1, 16-21, DOI: 10.1080/10426507.2011.568025
To link to this article: http://dx.doi.org/10.1080/10426507.2011.568025
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Phosphorus, Sulfur, and Silicon, 187:16–21, 2012
Copyright ꢀC 2011 Zhejiang University of Technology
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.568025
A FACILE OXIDATION OF THIOLS TO DISULFIDES
CATALYZED BY CoSALEN
Cheng-Xia Tan,1 Li-Yan Pan,1 Guo-Fu Zhang,1
and Yong-Shu Li2
1College of Chemical Engineering and Materials Sciences, Zhejiang University
of Technology, Hangzhou, P. R. China
2College of Pharmaceutical Sciences, Zhejiang University of Technology,
Hangzhou, P. R. China
GRAPHICAL ABSTRACT
Abstract A convenient and facile catalytic oxidation of thiols to the corresponding disulfides
is described using CoSalen as the catalyst and air as the oxidizing agent. This new approach
provides an efficient method for the preparation of symmetrical disulfides in high yields and
under mild conditions.
[Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental
resource: Spectroscopic Identification of Products 3a–3l.]
Keywords CoSalen; oxidation; thiol; disulfide; catalysis
INTRODUCTION
Catalytic oxidation is a reaction of high interest for both industrial and academic
research.1 There is a strong need for studying this powerful reaction, particularly toward
Received 1 January 2011; accepted 23 February 2011.
We are grateful to the financial support (grant no. Y307008) from Zhejiang Provincial Natural Science
Foundation and for the review of the manuscript by Dr. Cassia S. Mizuno.
Address correspondence to Yong-Shu Li, College of Pharmaceutical Sciences, Zhejiang University of
Technology, 18, Chaowang Road, Hangzhou, P. R. China. E-mail: liyongshu@zjut.edu.cn
16

OXIDATION OF THIOLS CATALYZED BY CoSALEN
17
the finding of catalysts that are more efficient, selective, and eco-friendly. Enzymes are
natural catalysts, well known for their high selectivity, operating at mild temperatures.
However, their use in an industrial environment is expensive and their handling is rather
difficult.2 The desire to mimic enzymatic system has created an extensive area of research
into synthetic porphyrin and Schiff base models of enzyme’s active sites, especially for
monooxygenase enzymes.3 Among them, N,Nꢁ-bis(salicylidene)ethylenediiminocobalt(II)
(CoSalen 1a) is the initially and most extensively investigated oxygen carrier due to its
structural similarity to the cytochrome P450 family found in biological systems.4 The
properties of CoSalen complexes have received considerable attention in the past several
years5 due to their oxygen-binding activity.
Although thiols can be easily oxidized to disulfides, they also suffer from overox-
idation. The oxidation does not stop at the disulfide formation and proceeds further to
sulfoxides and sulfones.6 Therefore, the careful choice of a proper oxidant and catalyst is
important. Thus, there have been extensive studies carried out to elaborate controlled condi-
tions such as halogens,7 Ph3PO/BTC,8 K+/CH3CN,9 iodine/hydrogen iodide,10 bromine,11
potassium dichromate,12 potassium permanganate/copper(II) sulfate,13 hydrogen peroxide
in trifluoroethanol,14 dimethyl sulfoxide,15 cerium(IV) salts,16 sulfuryl chloride,17 cesium
fluoride on celite,18 N-phenyltriazolinedione,19 silica-supported cobalt(II) tetrasulfoph-
thalocyanine,20 monochloro poly(styrenehydantoin) beads,21 calcium hypochlorite,22 1,3-
dibromo-5,5-dimethylhydantoin,23 potassium phosphate,24 enzymes,25 and electrochemical
techniques.26
Although these previously reported methods are very effective, most if not all of
them suffer from drawbacks including the use of expensive, rare, or toxic reagents and
metal oxidants, low yields, long reaction times, high reaction temperatures, or the risk of
overoxidation of the disulfides to sulfoxides. Mn(III)Salen27 offered the oxidation of thiols
to disulfides using hydrogen peroxide as the oxidant.
Herein, we report a facile, convenient, and efficient catalytic oxidation of thiols to the
corresponding disulfides using N,Nꢁ-bis(salicylidene)ethylenediiminocobalt(II) (CoSalen
1a) and its derivatives (1b–d) using air as the oxidant (Scheme 1).
RESULTS AND DISCUSSION
Initially, a test reaction using 2-thiobenzothiazole as reagent was performed. Among
the solvents tested, ethanol gave the best results. The temperature of 50 ◦C gave the highest
yield of 93% (entries 1–4, Table 1). Subsequently, the effect of the amount of CoSalen on
the reaction efficiency was studied. It was observed that 2.5% (mol/eq.) of CoSalen was
optimum for this reaction. The oxidation did not occur in the absence of CoSalen (entry 5,
Table 1).
CoSalens 1b–d were also tested in the oxidation of thiols to disulfides under the same
reaction conditions. The results are shown in Table 2.
As it can be seen from Table 2, CoSalens 1b and 1d showed higher oxidation efficiency
than 1a and 1c, respectively. The results indicated that an electron-donating group such
as methoxy may increase the oxygen-binding ability. In addition, the lower oxidation
efficiency of 1a and 1b in comparison with that of 1c and 1d, respectively, possibly shows
that iso-propyl groups may cause some steric hindrance and reduces the oxygen-binding
ability (Table 2).

18
C.-X. TAN ET AL.
Scheme 1
Table 1 Oxidative coupling of 2-thiobenzothiazole under different conditionsa
Entry
CoSalen (1a) (mmol)
Time (min)
Temperature (◦C)
Yieldb (%)
1
2
3
4
5
6
7
8
9
0.025
0.025
0.025
0.025
None
0.01
0.04
0.06
0.1
120
120
50
20
40
50
70
50
50
50
50
50
0
85
92
93
0
91
93
92
92
50
360
120
60
50
50
aAll reactions were carried out using 2-thiobenzothiazole (1 mmol), ethanol (10 mL), and 2.5% (mol/eq.) of
CoSalen 1a.
bIsolated yields based on 2-thiobenzothiazole.
Table 2 Oxidative coupling of 2-thiobenzothiazole catalyzed by different CoSalensa
Entry
CoSalen
Time (min)
Temperature (◦C)
Yieldb (%)
1
2
3
4
1a
1b
1c
1d
50
50
50
50
50
50
50
50
92
97
87
90
aAll reactions were carried out using 2-thiobenzothiazole (1 mmol), ethanol (10 mL), and CoSalen complex
(0.025 mmol).
bIsolated yields based on 2-thiobenzothiazole.

OXIDATION OF THIOLS CATALYZED BY CoSALEN
19
Table 3 Aerobic oxidative coupling of thiols to disulfides catalyzed by CoSalen 1aa
Substrate
Time
(min)
Yieldb
(%)
Disulfides
mp (◦C)
(Literature)
Entry
(2)
(3)
mp (◦C)
1
2
3
4
5
6
7
8
9
2-Thiobenzothiazole
Benzenethiol
50
60
60
50
40
70
50
60
20
90
720
92
90
91
92
94
90
91
90
95
88
80
3a
3b
3c
3d
3e
3f
3g
3h
3i
174∼176
60∼61
45
72∼73
39∼41
74∼77
Oil
288∼289
71∼72
Oil
177∼17928
6120b
p-Methylbenzenethiol
p-Chlorobenzenethiol
p-Methoxybenzenethiol
p-Aminobenzenethiol
m-Chlorobenzenethiol
Thiosalicylic acid
3,5-Bis(trifluoro-methyl)benzenethiolc
3,4-difluorobenzenethiol
Propane-2-thiol
4520b
7220b
4320b
74∼7629
Oil20b
288∼29030
74∼7531
Oil9
10
11
3j
3k
Oil
Oil32
aThe reactions were carried out using 1 mmol of substrate in 10 mL of ethanol at 50 ◦C with 0.025 mmol of
CoSalen 1a and bubbling of air into ethanol.
bIsolated yields based on the thiols.
cThe reaction was carried out at room temperature.
With optimized conditions in hand, we explored the scope of this process with
respect to thiol structure (Table 3). The catalytic oxidation occurred smoothly with excellent
selectivity and yield. No sulfoxides or sulfones were detected by gas chromatography (GC)
in the reaction mixtures.
CONCLUSIONS
In summary, we have developed an experimentally simple CoSalen-catalyzed aerobic
oxidation of thiols to disulfides using air as the oxidant. Although the exact mechanism
of this transformation is still unclear, this catalytic oxidation system is clean, selective,
and very effective. Further oxidation reactions using this system are in progress in our
laboratory.
EXPERIMENTAL
All chemicals were used as received from different commercial sources without
further purification. The CoSalen complexes 1a–d were prepared by a procedure similar
to that reported by R. H. Bailes.33 Melting points were determined on a digital melting
point apparatus WRS-1B and are uncorrected. Infrared (IR) spectra were recorded as KBr
1
pellets on a Nicolet Avatar-370 infrared spectrophotometer. H NMR spectra (500 MHz)
were measured on a Varian 500 instrument using CDCl3 or DMSO-d6 as the solvent with
tetramethylsilane as an internal standard. Mass spectra (MS) were recorded on a Finnigan
Trace DSQ (EI, 70 eV) spectrometer.
General Procedure for the Oxidation of Thiols
To CoSalen 1a (8.1 mg, 0.025 mmol) in ethanol (10 mL), 2-thiobenzothiazole (167
mg, 1.00 mmol) was added and air was bubbled through the reaction mixture. The reaction
mixture was stirred at 50 ◦C until thin layer chromatography indicated the disappearance of

20
C.-X. TAN ET AL.
the starting material. Evaporation of the solvent left the crude product, which was purified
by column chromatography over silica gel (hexane) to provide pure 2,2-dibenzothiazyl
disulfide as a light yellow solid. All the isolated disulfide compounds are known and they
were identified through comparison of IR, 1H NMR, MS, and melting points with literature
data. All of the spectra are in excellent agreement with the literature. As the products have
all been previously reported and referenced in Table 3, the 1H NMR data are presented in
the Supplemental Materials.
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