Oxidation of thiols using K2S2O8 in ionic liquid

Article abstract of DOI:10.1080/10426500802417000

A green, straightforward, and novel method for oxidation of thiols to the corresponding disulfides is reported using K2S2O8 in the ionic liquid 1-butyl-3-methylimidazolium bromide [(bmim)Br] at 65-70C. The corresponding disulfides were obtained in excellent yield and short reaction time.

Full text of DOI:10.1080/10426500802417000

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Phosphorus, Sulfur, and Silicon
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Oxidation of Thiols Using K 2 S 2
O 8 in Ionic Liquid
Abdol R. Hajipour a b , Majid Mostafavi b & Arnold E.
Ruoho a
a Department of Pharmacology, University of
Wisconsin, Medical School, Madison, Wisconsin, USA
b Pharmaceutical Research Laboratory, College of
Chemistry, Isfahan University of Technology, Isfahan,
Iran
Published online: 22 Jun 2009.
To cite this article: Abdol R. Hajipour , Majid Mostafavi & Arnold E. Ruoho (2009)
Oxidation of Thiols Using K 2 S 2 O 8 in Ionic Liquid, Phosphorus, Sulfur, and Silicon and
the Related Elements, 184:7, 1920-1923, DOI: 10.1080/10426500802417000
To link to this article: http://dx.doi.org/10.1080/10426500802417000
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Phosphorus, Sulfur, and Silicon, 184:1920–1923, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802417000
Oxidation of Thiols Using K2S2O8 in Ionic Liquid
Abdol R. Hajipour,1,2 Majid Mostafavi,2 and Arnold E.
Ruoho1
1Department of Pharmacology, University of Wisconsin, Medical School,
Madison, Wisconsin, USA
2Pharmaceutical Research Laboratory, College of Chemistry, Isfahan
University of Technology, Isfahan, Iran
A green, straightforward, and novel method for oxidation of thiols to the cor-
responding disulfides is reported using K S O8 in the ionic liquid 1-butyl-3-
2
2
methylimidazolium bromide [(bmim)Br] at 65–70◦C. The corresponding disulfides
were obtained in excellent yield and short reaction time.
Keywords Disulfides; ionic liquid; K2S2O8; oxidation; thiols
INTRODUCTION
Oxidation of thiols to the corresponding disulfides under mild condi-
tions is a useful reaction from the point of view of biological and indus-
trial applications.1 Since thiols can be over-oxidized, extensive research
has been performed to control their oxidation at the disulfide stage.2
The oxidation coupling of thiols to disulfides is an essential reaction
in the synthesis of natural products, and further oxidation to disul-
fide S-oxides (thiosulfinates), 1,1-dioxides (thiosulfonates), and sulfonic
acids is possible. Weak S-S bonds in these compounds impart high
reactivity,3 and in natural products, these moieties and related cyclic
analogues are associated with interesting biological activity.4
Ionic liquids (IL) have frequently been used as green solvents in
place of conventional organic solvents,5–9 being superior due to their
Received 28 April 2008; accepted 14 August 2008.
We gratefully acknowledge the funding support received for this project from the
Isfahan University of Technology (IUT), I.R. Iran (A. R. H.), and Grants GM 033138,
MH 065503, and NS 033650 (A. E. R.) from the National Institutes of Health, USA.
Further financial support from Center of Excellence in Sensor Chemistry Research (IUT)
is gratefully acknowledged.
Address correspondence to Abdol R. Hajipour, Dept. of Pharmacology, University of
Wisconsin, Medical School, 1300 University Avenue, Madison, WI 53706-1532, USA.
E-mail: arhajipour@facstaff.wisc.edu
1920

Oxidation of Thiols Using K S O in Ionic Liquid
1921
2
2 8
extremely low vapor pressure, excellent thermal stability, reusability,
and ability to dissolve many organic and inorganic substrates.10 The
application of ionic liquids as solvents and catalysts has been reported
for a variety of functional group transformations, but their use as acid
catalysts under solvent-free conditions deserves more attention.11
RESULTS AND DISCUSSION
In connection with our ongoing program on developing new methods
for organic functional groups transformation,12–17 we wish to report
the applications of potassium persulfate, K2S2O8, in ionic liquid, 1-
butyl-3-methylimidazolium [(bmim)Br] and the use of this efficient,
inexpensive, and mild reagent for oxidizing a variety of aliphatic and
aromatic thiols.
This method is effective for coupling of aliphatic and aromatic thiols
to the corresponding disulfides. It was found that only traces of fur-
ther oxidation products such as S-oxides (thiosulfinates), 1,1-dioxides
(thiosulfonates), and sulfonic acids are formed. A series of thiols was ox-
idized to disulfides rapidly using this reagent. Primary alcohol, amine,
carboxylic acid, ester, and methoxy functional groups were unaffected
during the oxidation (Scheme 1 and Table I).
K2S2O8/Ionic Liquid
R1SH
R1S-SR1
70 C
R1 = Alkyl or Aryl
SCHEME 1
In conclusion, this is a new and green method for oxidation of thiols
to the corresponding disulfides. The green chemistry, straightforward
workup, mild reaction conditions, high yields of the products, and short
reaction time make this a useful method for oxidation of thiols to disul-
fides.
EXPERIMENTAL
General
Yields refer to isolated pure products after column chromatography.
The products were characterized by comparison of their spectral (IR,
1H NMR) and physical data with those of authentic samples.15 All H
1
NMR spectra were recorded at 300 MHz in CDCl3 relative to TMS (0.00
ppm), and IR spectra were recorded on Shimadzu 435 IR spectrometer.

1922
A. R. Hajipour et al.
TABLE I Oxidation of Thiols to Disulfidesa,b,c
Reaction Time
(min) Yield (%)
Mp or Bp/mmHg ◦
(Lit) [15]
C
Reactant
Product
(C6H5S)2
C6H5SH
10
15
20
20
10
20
10
20
20
20
25
20
25
25
20
25
30
30
30
20
25
94
93
88
84
94
90
91
90
90
92
92
98
84
84
86
90
80
84
83
92
84
59–61 (59–61)[15]
47–48 (47–48)[15]
44–45 (44–45)[15]
76–77 (75–77) [15]
–21 (–21)[15]
72–73 (72–73)[15]
197–198 (198–199) [15]
69–70 (69–70)[15]
4-MeC6H4SH
4-MeOC6H4SH
4-NH2C6H4SH
3-MeC6H4SH
4-ClC6H4SH
(4-MeC6H4S)2
(4-MeOC6H4S)2
(4-NH2C6H4S)2
(3-MeC6H4S)2
(4-ClC6H4S)2
2-Me2OCC6H4SH (2-MeOOCC6H4S)2
C6H5CH2SH
4-NO2C6H4SH
2-PyridylSH
4-PyridylSH
CyclopentylSH
CyclohexylSH
(C6H5 CH2S)2
(4-NO2C6H4S)2
(2-PyridylS)2
(4-PyridylS)2
(CyclopentylS)2
(CyclohexylS)2
177–178 (172–178)[15]
52–53 (52–53)[15]
76–77 (76–77)[15]
105–106 (105–106)[15]
124 129 (124–129)[15]
Thick oil (156–1148/2)[15]
157–159 (157–159)[15]
139–141 (138–139)[15]
94–96/6 (94–96/6)[15]
oil (117–119/6)[15]
oil (152–154/6)[15]
Semi solid (143–147/5)[15]
–
HO-CH2CH2SH (HO-CH2CH2S)2
H2OCCH2CH2SH (HOOCCH2CH2S)2
HOOCCH2SH
CH3(CH2)3SH
CH3(CH2)4SH
CH3(CH2)6SH
CH3(CH2)7SH
(HOOCCH2S)2
(CH3(CH2)3S)2
(CH3(CH2)4S)2
(CH3(CH2)6S)2
(CH3(CH2)7S)2
1-(HSCH2)2C6H4 (-SCH2C6H4CH2S-)n
aConfirmed by comparison with authentic samples (IR, TLC, and NMR).
bOxidant/thiol/ionic liquid (1.0:1.0:1.0).
cYield of isolated pure product after chromatography or distillation.
All reactions were carried out at room temperature in a hood with
strong ventilation.
Procedure for Oxidation of Thiols to the Corresponding
Disulfide: Typical Procedure
A mixture of thiophenol (10 mmol, 1.1 g) , K2S2O8(2.7 g, 10 mmol),
and [bmim]Br (2.7 g, 10 mmol) was ground for 1 min with a mortar
and pestle. The mixture was transferred to a round-bottomed flask and
kept at 65–70◦C for the time specified in Table I. The progress of the
reaction was followed by TLC/GC. After the reaction was completed
(Table I), 20 mL of diethyl ether was added and the reaction mixture
was filtered through a sintered glass funnel, the filtrate was transferred
to a separatory funnel and washed with NaHCO3 (5%). The organic
layer was dried over anhydrous Na2SO4, and the solvent was removed
in vacuo. The residue was purified through a short column of silica gel

Oxidation of Thiols Using K S O in Ionic Liquid
1923
2
2 8
(cyclohexane:EtOAc, 3:1) to obtain diphenyl disulfide in 94% yield, mp
1
59–61◦C [Lit.16 mp 58–61◦C]. H NMR (CDCl3, 300 MHz): δ = 7.62–
7.48 (m, 4H), 7.42–7.20 (m, 6H). IR (KBr): 459, 470, 687, 734, 1435,
1474, 1572, 3050 cm−1
.
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