Fe(HSO4)3 and Fe(HSO4)3/DMSO as efficient, heterogeneous, and reusable catalyst systems for the oxidative coupling of thiols

Article abstract of DOI:10.1080/10426500802704654

Fe(HSO₄)₃ has been used as a heterogeneous, efficient, and recyclable catalyst in ethanol for the selective oxidation of thiols to their corresponding disulfides. The same results were obtained under identical conditions using catalytic amounts of Fe(HSO₄)₃ in the presence of DMSO. Different types of aliphatic, aromatic, and heteroaromatic thiols have been used in the reaction, and in all cases the products were obtained in good to excellent yields.

Full text of DOI:10.1080/10426500802704654

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Fe(HSO4)3 and Fe(HSO4)3/DMSO
as Efficient, Heterogeneous,
and Reusable Catalyst Systems
for the Oxidative Coupling of
Thiols
H. Eshghi a , M. Bakavoli a , H. Moradi a & A.
Davoodnia b
a Department of Chemistry, School of Sciences,
Ferdowsi University of Mashhad, Mashhad, Iran
b Department of Chemistry, School of Sciences,
Islamic Azad University, Mashhad Branch, Mashhad,
Iran
Published online: 03 Nov 2009.
To cite this article: H. Eshghi , M. Bakavoli , H. Moradi & A. Davoodnia (2009)
Fe(HSO4)3 and Fe(HSO4)3/DMSO as Efficient, Heterogeneous, and Reusable Catalyst
Systems for the Oxidative Coupling of Thiols, Phosphorus, Sulfur, and Silicon and the
Related Elements, 184:11, 3110-3118, DOI: 10.1080/10426500802704654
To link to this article: http://dx.doi.org/10.1080/10426500802704654
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Phosphorus, Sulfur, and Silicon, 184:3110–3118, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802704654
Fe(HSO4)3 and Fe(HSO4)3/DMSO as Efficient,
Heterogeneous, and Reusable Catalyst Systems for the
Oxidative Coupling of Thiols
H. Eshghi,1 M. Bakavoli,1 H. Moradi,1 and A. Davoodnia2
1Department of Chemistry, School of Sciences, Ferdowsi University of
Mashhad, Mashhad, Iran
2Department of Chemistry, School of Sciences, Islamic Azad University,
Mashhad Branch, Mashhad, Iran
Fe(HSO4)3 has been used as a heterogeneous, efficient, and recyclable catalyst in
ethanol for the selective oxidation of thiols to their corresponding disulfides. The
same results were obtained under identical conditions using catalytic amounts of
Fe(HSO4)3 in the presence of DMSO. Different types of aliphatic, aromatic, and
heteroaromatic thiols have been used in the reaction, and in all cases the products
were obtained in good to excellent yields.
KEYWORDS Disulfide; DMSO; Fe(HSO4)3; heterogeneous; oxidation; thiol
INTRODUCTION
The oxidative coupling of thiols to disulfides under mild conditions
is of practical importance in synthetic chemistry1 and biochemistry.2
Disulfides have found industrial applications as vulcanizing agents3
and are important synthetic intermediates with many applications in
organic synthesis. They can be used to prepare sulfinyl and sulfenyl
compounds.4 In biological systems, thiols are oxidized by flavins, cy-
tochromes, and dehydroascorbic acid to control the cellular redox poten-
tial and prevent oxidative damage.5 Recently, we have reported6 a new
application of disulfides in regioselective ring opening of epoxides to
halohydrins with elemental halogens. Thiols can be easily over-oxidized
and, therefore, extensive studies have been carried out to develop con-
trolled conditions to disulfide preparation7 such as bromine,8 potas-
sium dichromate,9 Sm/BiCl3,10 potassium permanganate/copper(II)
Received 12 September 2008; accepted 9 December 2008.
Address correspondence to H. Eshghi, Department of Chemistry, School of Sci-
ences, Ferdowsi University of Mashhad, Mashhad 91775-1436, Iran. E-mail: hes-
hghi@ferdowsi.um.ac.ir
3110

Fe(HSO4)3 and Fe(HSO4)3/DMSO
3111
sulfate,11 hydrogen peroxide in trifluoroethanol,12 tungstate sulfuric
acid,13 I2/DMSO,14 HMDS/DMSO,15 MoO2Cl2(dmso)2,16 and Mn(III)
Schiff-base complex.17 Enzymatic18 and electrochemical19 methods are
also known to perform this oxidative transformation. However, most of
these methods suffer from one or more disadvantage, such as long re-
action times; difficult workup; lack of general applicability to thiol sub-
strates bearing alkyl, aryl, and heteroaromatic moieties; formation of
over-oxidation products leading to lower yields; or use of stoichiometric
excess amounts of the expensive, rare, or toxic reagents for successful
oxidation. Thus, there is still a need to develop a simple, mild, clean,
and efficient oxidative method that would produce the target disulfides
in high yields without complicated workup procedures.
Recently, ferric hydrogensulfate has emerged as a promising solid
acid catalyst for acid catalyzed reactions, such as the Schmidt reac-
tion,20 functional group protections,21,22 and Friedel–Crafts acylation.22
We wish to report an efficient and simple method for oxidative cou-
pling of thiols into the corresponding disulfides using molecular oxygen
and/or DMSO catalyzed by Fe(HSO4)3 under mild conditions. In this
regard, molecular oxygen is considered as an ideal ‘‘green’’ oxidant due
to its strength and lack of toxic byproducts.
RESULTS AND DISCUSSION
Fe(HSO4)3 has the special advantages of ferric salts such as its insolu-
bility in organic solvents, and this makes its recovery very convenient.
It can be easily prepared from commercially available starting mate-
rials, stored and used after several months, and can be treated with
supports and co-catalysts leading to a wide variety of reactions.
In order to determine the most appropriate reaction conditions and
evaluate the catalytic efficiency of Fe(HSO4)3, initially a model study
was carried out on the synthesis of diphenyl disulfide (2a) for opti-
mization studies (Scheme 1). Among the tested solvents at different
temperatures to facilitate the transformation of (1a), ethanol was the
most effective and gave the best conversion and highest yield in 45 min
at room temperature (Table I, entry 9). The ferric hydrogenesulfate
was easily recovered and reused for the next set of oxidation reactions
without significant decrease in activity even after five runs (Table I,
entries 9–13).
Further, when the oxidative coupling of thiophenol was carried out
using a different amount of Fe(HSO4)3, the reaction was found to reach
completion faster with an increase in amount of Fe(HSO4)3 up to 1
mmol (Table I, entries 9, 14, and 15). However, the oxidation of thiol in

3112
H. Eshghi et al.
SCHEME 1
the absence of catalyst did not occur even under extension of reaction
time to several days, and unreacted thiol was completely recovered
(Table I, entry 16).
Interestingly, it was found that even 10 mol% Fe(HSO4)3 is an ef-
ficient catalyst when the reaction was carried out in the presence of
dimethylsulfoxide and gave exclusively (2a) in 91% yield in 1.5 h (Table
I, entry 17). Then we examined the same oxidation reaction of o-amino
thiophenol (1b) under a catalytic amount of catalyst (0.1 mmol) in the
presence of different amounts of DMSO at room temperature (Table I,
TABLE I Optimization of the Oxidative Coupling Reaction on Thiols
by Fe(HSO4)3
Fe(HSO4)3
(mmol)
DMSO
(mmol)
Solvent,
Time Yield
(h)
Entry Substrate
Temperature (◦C)
(%)a
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1
1
1
1
1
1
1
1
1
1
1
1
1
0.5
0.1
0
0.1
0.1
0.1
0.1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
3
3
2
1
CH2Cl2, 25
CH3CN, 25
THF, 25
n-Hexane, 25
CH3OH, 25
4
2
1.5
5
41
45
80
35
89
87
37
80
95
92
94
92
90
73
50
0
1
C2H5OH/H2O (50%), 25
C2H5OH, 0
1.2
5.5
0.4
0.75
0.5
0.8
0.9
1
2.5
6.5
7
1.5
0.58
0.9
1.6
C2H5OH, 55
C2H5OH, 25
C2H5OH, 25
C2H5OH, 25
C2H5OH, 25
C2H5OH, 25
C2H5OH, 25
C2H5OH, 25
C2H5OH, 25
C2H5OH, 25
C2H5OH, 25
C2H5OH, 25
C2H5OH, 25
10b
11c
12d
13e
14
15
16
17
18
19
20
91
96
86
85
aIsolated yields.
b–eRefer to the recycling of catalyst in new subsequent runs.

Fe(HSO4)3 and Fe(HSO4)3/DMSO
3113
Entries 18–20). It was found that the optimum reaction rate and yield
could be achieved by using three equivalents of DMSO in a catalytic
system (Table I, Entry 18).
In order to evaluate the generality of the process of oxidative cou-
pling, various aliphatic, aromatic, and heteroaromatic thiols were then
examined using the optimized reaction conditions, and in both selected
approaches, the oxidation was performed in good to excellent yields.
The general reaction is illustrated according to the Scheme 2, and the
results are summarized in Table II.
SCHEME 2
All reactions were performed in 8–480 min, and coupling of a vari-
ety of thiols confirmed the general applicability and practical utility of
this method. All the reactions were carried out at room temperatures.
As shown in Table II, the aromatic thiols having electron-donating sub-
stituents showed a high reactivity and selectivity (Table II, entries 1–4).
Thiols with tautomeric thione and thiol forms had less reactivity than
aromatic and aliphatic thiols (Table II, entry 5). Aliphatic thiols with
short chains especially having an electron donating substituent (NH2)
in the chain showed a higher reactivity and selectivity in 8–60 min
during the two reaction conditions (Table II, Entries 8–9) than long
chains and those having carboxyl group (Table II, Entries 7, 10–11).
The purity of the products was determined by 1H NMR and IR spectra,
which showed the exclusive formation of the corresponding disulfides
whose structure was confirmed by melting point comparison. The sug-
gested reaction mechanism is presented in Scheme 3. Although the
exact mechanism of these transformations is still unclear, the catalytic
system accelerated with DMSO probably involves the formation of an
SCHEME 3

3114

3115

3116
H. Eshghi et al.
intermediate Fe(IV) or Fe(V) in the presence of dissolved oxygen in
ethanol.
In conclusion, the results indicate that ferric hydrogene sulfate is an
efficient and reusable heterogeneous catalyst for the oxidative coupling
of thiols to disulfides. It has the capacity to be treated by other types
of co-oxidants such as DMSO to operate more efficiently. Simplification
of handling procedure; fewer byproducts; green chemistry; availibility,
stability, and cheapness of catalyst; and clean workup with high yields
make these methods as useful methodology for practical synthesis.
EXPERIMENTAL
All materials and solvents were obtained from Merck chemical com-
pany (Germany) and Fluka (Switzerland). Melting points were deter-
mined in open capillary tubes in an Electrothermal IA 9000 melting
point apparatus. IR spectra were recorded on a Shimadzu IR 470 spec-
1
trophotometer. H NMR spectra were recorded on a Bruker-100 MHz
instrument using tetramethylsilane (TMS) as an internal standard.
Ferric hydrogensulfate was prepared according to previously reported
procedure.20
General Procedure for the Selective Oxidative Coupling of
Thiols to Disulfides Catalyzed by Fe(HSO4)3
A mixture of thiol (1 mmol) and Fe(HSO4)3 (0.35 g, 1 mmol) in ethanol (5
mL) was stirred at room temperature until TLC indicated the reaction
was complete. After the completion, the reaction mixture was filtered,
and the organic solvent was then removed. The resulting residue was
washed with a minimal volume of CH2Cl2:n-hexane (1:9) to give the
crude product in high yield.
General Procedure for the Selective Oxidative Coupling of
Thiols to Disulfides Catalyzed by Fe(HSO4)3/DMSO
A mixture of thiol (1 mmol), DMSO (3 mmol), and Fe(HSO4)3 (0.035
g, 0.1 mmol) in ethanol (5 mL) was stirred at room temperature until
TLC indicated the reaction was complete. After the completion, the
reaction mixture was filtered and the organic solvent was removed. The
resulting residue was then dissolved in CH2Cl2 (5 mL), washed with
water (2 × 10 mL), and dried with anhydrous Na2SO4. After solvent
evaporation, the corresponding disulfide was obtained in high yield.

Fe(HSO4)3 and Fe(HSO4)3/DMSO
3117
The products were characterized by comparison of their physical and
spectral data with those reported in the literature.23–29
REFERENCES
[1] (a) E. T. Denisov and I. B. Afanas’ev, Oxidation and Antioxidants in Organic Chem-
istry and Biology (Taylor & Francis, Boca Raton, FL, 2005); (b) S. Oae, Ed., Organic
Sulfur Chemistry: Structure and Mechanism (CRC Press, Boca Raton, FL, 1991);
(c) R. J. Cremlyn, An Introduction to Organosulfur Chemistry (Wiley and Sons, New
York, 1996).
[2] (a) G. Roy and G. Mugesh, Phosphorus, Sulfur, and Silicon, 180, 891 (2005); (b) D.
C. Jocelyn, Biochemistry of the Thiol Groups (Academic, New York, 1992); (c) M. C.
Fournie-Zaluski, P. Coric, S. Turcaud, L. Bruetschy, E. Lucas, F. Noble, and B. P.
Roques, J. Med. Chem., 35, 1259 (1992).
[3] (a) K. Ramadas and N. Srinivasan, Synth. Commun., 25, 227 (1995); (b) H. L. Fisher,
Ind. Eng. Chem., 42, 1978 (1950).
[4] (a) J. Lam, H. Bilddose, L. P. Christensen, and T. Thomsen, Acta Chem. Scand. Ser.,
B, 43, 799 (1989); (b) V. Srivastav, R. Gupta, and R. R. Guptam, Indian J. Chem.,
39B, 223 (2000); (c) P. Metzner, Synthesis, 1185 (1992); (d) E. Kuhle, The Chemistry
of the Sulfenic Acids (Georg Thieme Verlag, Stuttgart, 1973); (e) I. B. Douglass and
R. V. Norton, J. Org. Chem., 33, 2104 (1968); (f) I. B. Douglass, J. Org. Chem., 39,
563 (1974).
[5] (a) I. Pe’er, C. E. Felder, O. Man, I. Silman, and J. L. Sussman, Proteins, 54, 20
(2004); (b) J. C. Bardwell, Mol. Microbiol., 14, 199 (1994); (c) N. Kharasch and A. S.
Arora, Phosphorus and Sulfur, 2, 1 (1976).
[6] H. Eshghi, S. F. Tayyari, Z. Rezvani-Amin, and H. Roohi, Bull. Korean Chem. Soc.,
29, 51 (2008).
[7] S. Oae, D. Fukushima, and Y. H. Kim, J. Chem. Soc. Chem. Commun., 407 (1977).
[8] M. H. Ali and M. McDermott, Tetrahedron Lett., 43, 6271 (2002).
[9] S. Patel and B. K. Mishra, Tetrahedron Lett., 45, 32 (2004).
[10] G. Lu and Y. Zhang, Synth. Commun., 28, 191 (1998).
[11] A. Shaabani and D. J. Lee, Tetrahedron Lett., 42, 5833 (2001).
[12] V. Kesavan, D. Bonnet-Delpon, and J.-P. Begue, Synthesis, 223 (2000).
[13] B. Karami, M. Montazerozohori, and M. H. Habibi, Phosphorus, Sulfur, and Silicon,
181, 2825 (2006).
[14] R. F. Lang, T. D. Ju, G. Kiss, C. D. Hoff, J. C. Bryan, and G. J. Kubas, Inorg. Chim.
Acta, 259, 317 (1997).
[15] B. Karimi, H. Hazarkhani, and D. Zareyee, Synthesis, 2513 (2002).
[16] R. Sanz, R. Aguado, M. R. Pedrosa, and F. J. Arnaiz, Synthesis, 856 (2002).
[17] H. Gholchoubian and F. Hosseinpoor, Catal. Commun., 8, 697 (2007).
[18] M. Sridhar, S. K. Vadivel, and U. T. Bhalerao, Synth. Commun., 28, 1499 (1998).
[19] S. L. S. Leite, V. L. Pardini, and H. Viertler, Synth. Commun., 20, 393 (1990).
[20] H. Eshghi, J. Chin. Chem. Soc., 53, 987 (2006).
[21] H. Eshghi, M. Rahimizadeh, and S. Saberi, Catal. Commun., 9, 2460 (2008).
[22] (a) H. Eshghi, M. Bakavoli, and H. Moradi, Chin. Chem. Lett., 19, 1423 (2008); (b) F.
Shirini, M. A. Zolfigol, P. Salehi, and M. Abedini, Curr. Org. Chem., 12, 183 (2008);
(c) P. Salehi, M. M. Khodaei, M. A. Zolfigol, and S. Zeinoldini, Synth. Commun., 33,
1367 (2003).
[23] J. Field and J. E. Lawson, J. Am. Chem. Soc., 80, 838 (1958).

3118
H. Eshghi et al.
[24] M. M Khodaei, I. Mohammadpour-Baltork, and K. Nikoofar, Bull. Korean Chem.
Soc., 24, 885 (2003).
[25] B. Karimi, M. Montazerozohori, and M. H. Habibi, Molecules, 10, 1358 (2005).
[26] A. S. Demir, A. C. Igdir, and A. S. Mahasneh, Tetrahedron, 55, 12399 (1999).
[27] H. Matsubara and R. M. Sasaki, Biochem. Biophys. Res. Commun., 35, 175 (1969).
[28] E. J. Mills and J. M. Taylor-Bogret, J. Am. Chem. Soc., 62, 1173 (1940).
[29] O. M. Lezina, S. A. Rubtsova, and A. V. Kuchin, Russ. Chem. Bull. Int. Ed., 22, 1877
(2003).