Arylglyoxals: A novel and efficient reagent for the oxidation of thiols to homodisulfides

Article abstract of DOI:10.1080/17415993.2010.550618

The stoichiometric oxidation of thiols to their corresponding homodisulfides by arylglyoxals has been described. The process has several advantages: high yields, short reaction times, simple experimental and work-up procedures. Figure Presented.

Full text of DOI:10.1080/17415993.2010.550618

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Arylglyoxals: a novel and efficient
reagent for the oxidation of thiols to
homodisulfides
Mohammad Hossein Mosslemin a , Mohammad Anary-Abbasinejad
a , Abolfazl Eshghi Movahhed a , Alireza Hassanabadi b & Saeedeh
Ghoroghchian a
a Department of Chemistry , Islamic Azad University , Yazd
Branch, PO Box 89195-155, Yazd , Iran
b Department of Chemistry , Islamic Azad University , Zahedan
Branch, PO Box 98135-978, Zahedan , Iran
Published online: 27 Jan 2011.
To cite this article: Mohammad Hossein Mosslemin , Mohammad Anary-Abbasinejad , Abolfazl
Eshghi Movahhed , Alireza Hassanabadi & Saeedeh Ghoroghchian (2011) Arylglyoxals: a novel and
efficient reagent for the oxidation of thiols to homodisulfides, Journal of Sulfur Chemistry, 32:2,
111-115, DOI: 10.1080/17415993.2010.550618
To link to this article: http://dx.doi.org/10.1080/17415993.2010.550618
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Journal of Sulfur Chemistry
Vol. 32, No. 2, April 2011, 111–115
Arylglyoxals: a novel and efficient reagent for the oxidation
of thiols to homodisulfides
Mohammad Hossein Mosslemina*, Mohammad Anary-Abbasinejada, Abolfazl Eshghi
Movahheda, Alireza Hassanabadib and Saeedeh Ghoroghchiana
aDepartment of Chemistry, Islamic Azad University, Yazd Branch, PO Box 89195-155, Yazd, Iran;
bDepartment of Chemistry, Islamic Azad University, Zahedan Branch, PO Box 98135-978, Zahedan, Iran
(Received 28 October 2010; final version received 21 December 2010)
The stoichiometric oxidation of thiols to their corresponding homodisulfides by arylglyoxals has been
described. The process has several advantages: high yields, short reaction times, simple experimental and
work-up procedures.
O
Ar
H
O
O
OH
RSSR
RSH
+
Ar
AcOH, reflux, 20min
Keywords: disulfides, thiols, oxidation, arylglyoxal, acetic acid
1. Introduction
Oxidation of thiols to their homodisulfides is an important transformation from both biological
and synthetic point of views (1, 2). Homodisulfides are important reagents in organic synthesis
and can be used for the preparation of sulfinyl and sulfenyl compounds (3). Thiols are easily
oxidized to homodisulfides (for a review, see (4a), and for a list of reagents, with references, see
(4b)). Hydrogen peroxide is the most common reagent (5)1 but many oxidizing agents give the
reaction, such as KMnO4/CuSO4 (6), Me2SO/I2 (7), Br2 under phase-transfer conditions (8),
Br2 on hydrated silica (9), sodium perborate (10), NaI/air (11), t-BuOOH/VO(acac)2 (12), SmI2
(13), PPh3 with a rhodium catalyst (14), dibromohydantoin (15) and cetyltrimethylammonium
dichromate (16). It can also be done electrochemically (17). Hydrogen peroxide 30% in hexaflu-
oroisopropanol converts thiols to disulfides (18) with Clayan on microwave irradiation (19), and
solventless reactions on MnO2 (20), PCC (21) or SO2Cl2 (22) are also effective. It has also been
done with the Burgess reagent (23).
*Corresponding author. Email: mhmosslemin@yahoo.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2011 Taylor & Francis
DOI: 10.1080/17415993.2010.550618
http://www.informaworld.com

112 M.H. Mosslemin et al.
However, some of these reagents suffer from disadvantages such as long reaction times,
toxicity, difficult work-up, preparation and instability (24). Consequently, there is still a need
for introducing readily available and stable reagents for the oxidation of thiols to homodisulfides.
Here, we wish to report the results of our studies on the reaction between thiols and arylglyoxals
by refluxing in glacial acetic acid.
2. Results and discussion
The reaction of the thiols 1 and arylglyoxals in refluxing glacial acetic acid leads to homodisulfides
2 in good yields (Scheme 1).
reflux, 20min
Scheme 1. The stoichiometric oxidation of thiols to homodisulfides by aryl glyoxals.
Table 1. The stoichiometric oxidation of thiols to corresponding homodisulfides with arylglyoxals (a–c).
Time
(min)
Yield (%)
(a, b, c)
Yield (%)
(22, 23, 26)
Mp
Entry
1
Thiol 1
Disulfide 2
(◦C)
S–S
SH
20
20
20
92, 91, 90
92, 91, 90
92, 89, 88
91, 90
98, –
44–145
44–45
60–61
S–S
S–S
S–S
SH
2
3
SH
97, 96
Br
SH
4
5
6
20
20
20
90, 89, 88
91, 89, 88
87, 86, 85
–, 95
97, 93
–, –
91–93
72–73
55–56
Br
Br
S–S
S–S
Cl
SH
Cl
Cl
SH
N
N
N
S–S
7
CH2SH
20
88, 86, 85
94, 93
67–69
8
9
10
11
n-C4H9SH
c-C6H11SH
n-C8H17SH
(n-C4H9S)2
(c-C6H11S)2
(n-C8H17S)2
20
20
20
20
88, 87, 85
87, 86, 85
86, 86, 85
86, 85, 85
97, –
–, –
94, –
95, –
Oil (8)
Oil (11)
Oil (22)
Oil (22)
(CH3)2CHCH2SH
((CH3)2CHCH2S)2
Notes: ap-NO2-phenylglyoxal; bCl-phenylglyoxal; cBr-phenylglyoxal.

Journal of Sulfur Chemistry 113
Table 2. Comparative reaction between 4-methylbenzenethiol and
p-nitrophenylglyoxal in several solvents.
Solvent
Temperature (◦C)
Time (min)
Yielda (%)
MeOH
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
80
20
80
80
20
20
26
55
Trace
32
62
92
MeOH, H+
CH3CN
H2O
H2O, H+
HOAc
Note: aIsolated yield.
Compounds 2 have been reported previously in the literature (Table 1). It was found that at least
20 min was needed for the reaction to go to completion.After completion and cooling, the homod-
isulfides were obtained directly in >85% yields. On the other hand, the reaction was checked in
several solvents. For this purpose, a mixture of 4-methylbenzenethiol and p-nitrophenylglyoxal
was stirred in different solvents under reflux conditions (Table 2). As Table 2 indicates, HOAc is
the best solvent. We utilized nitro and halophenylglyoxal in the reaction. Interestingly, the results
showed that these substituents had no significant effect on the reaction times and the yields.
Phenylglyoxals were synthesized by the oxidation of acetophenones with selenium dioxide in the
presenceofdioxaneorethylalcoholasasolvent(25). By-product 3a (2-hydroxy-1-(4-nitrophenyl)
ethanone) was obtained by chromatography of the remaining reaction and characterized by IR,
elemental analysis, 1H NMR and 13C NMR spectra.Although the mechanistic details of the above
reaction are not known, a plausible mechanism may be advanced to rationalize products formation
(Scheme 2).
Scheme 2. Suggested mechanism for the formation of compounds 2 and 3.
In summary, we report herein that the reaction between thiols and arylglyoxals by refluxing in
glacial acetic acid leads to homodisulfides in good yields. The advantages of the reported method
are simple available starting materials, short reaction time, simple work-up, neutral reaction
conditions and high yields. We suggest that this method could be used for the oxidation of a wide
variety of thiols.
3. Experimental
Melting points were determined with an Electrothermal 9100 apparatus. Elemental analyses were
performed using a Costech ECS 4010 CHNS-O analyzer at analytical laboratory of Islamic Azad
UniversityYazd branch. Mass spectra were recorded on a FINNIGAN-MAT 8430 mass spectrom-
eter operating at an ionization potential of 70 eV. IR spectra were recorded on a Shimadzu IR-470
spectrometer. 1H and 13C NMR spectra were recorded on a Bruker DRX-500Avance spectrometer
as a solution in CDCl3 using TMS as the internal standard. The chemicals used in this work were
purchased from Fluka (Buchs, Switzerland) and were used without further purification.

114 M.H. Mosslemin et al.
3.1. General procedure
To a magnetically stirred solution of thiol (2 mmol), a solution of arylglyoxal (1 mmol) in 20 mL
glacial acetic acid was added. The resulting mixture was stirred for 20 min under reflux. After
cooling, the crude homodisulfide was isolated by filtration and was purified by recrystallization
in ethanol and water (3:1).
3.2. 2-Hydroxy-1-(4-nitrophenyl) ethanone (3)
Cream colored solid, m.p. 179–181 ◦C. IR (KBr) (νmax, cm−1): 1703 (C O), 3525 (OH).Analysis:
=
Calcd for C8H7NO4 (181): C, 53.04; H, 3.89; N, 7.73%, Found: C, 53.16; H, 3.94; N, 7.61%. 1H
NMR (500.1 MHz, CDCl3): δ 3.34 (1H, s, OH), 5.29 (2H, s, CH2), 8.26 (2CH, d, 3JHH = 8 Hz,
2H), 8.34 (2CH, d, 3JHH = 8 Hz, 2H). 13C NMR (CDCl3): δ = 195.7 (C O), 150.2, 139.0, 131.2,
=
124.0 9 (4CH aromatic), 90.5 (CH2).
Acknowledgements
The authors gratefully acknowledge the financial support from the Research Council of Islamic Azad University of Yazd
and The Islamic Azad University of Zahedan of Iran.
Note
1. It has been pointed out that, nevertheless, H2O2 is not a very good reagent for this reaction, since it gives sulfonic
acids as well as disulfides.
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