Efficient and selective oxidation of thiols to disulfides by 1,4-diazabicyclo[2.2.2]octane-di-N-oxide-diperhydrate under neutral and heterogeneous conditions

Article abstract of DOI:10.1080/10426500490466427

1,4-Diazabicyclo[2.2.2]octane-di-N-oxide-di-perhydrate selectively oxidizes thiols to disulfides in acetonitrile in good yields. The method is generally useful for a wide variety of thiols.

Full text of DOI:10.1080/10426500490466427

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Phosphorus, Sulfur, and Silicon and the Related
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EFFICIENT AND SELECTIVE OXIDATION OF THIOLS TO
DISULFIDES BY 1,4-DIAZABICYCLO[2.2.2]OCTANE-
DI-N-OXIDE-DI-PERHYDRATE UNDER NEUTRAL AND
HETEROGENEOUS CONDITIONS
Peyman Salehi a , Mohammad Ali Zolfigol b & Leila Bazaz Tolami a
a Department of Phytochemistry, Medicinal Plants Research Institute, Shahid Beheshti
University, Evin, Tehran, Iran
b Department of Chemistry, Faculty of Science, Bu-Ali Sina University, Hamadan, Iran
Version of record first published: 16 Aug 2010.
To cite this article: Peyman Salehi , Mohammad Ali Zolfigol & Leila Bazaz Tolami (2004): EFFICIENT AND SELECTIVE
OXIDATION OF THIOLS TO DISULFIDES BY 1,4-DIAZABICYCLO[2.2.2]OCTANE-DI-N-OXIDE-DI-PERHYDRATE UNDER NEUTRAL AND
HETEROGENEOUS CONDITIONS, Phosphorus, Sulfur, and Silicon and the Related Elements, 179:9, 1777-1781
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Phosphorus, Sulfur, and Silicon, 179:1777–1781, 2004
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490466427
EFFICIENT AND SELECTIVE OXIDATION
OF THIOLS TO DISULFIDES BY
1,4-DIAZABICYCLO[2.2.2]OCTANE-DI-N-OXIDE-DI-
PERHYDRATE UNDER NEUTRAL
AND HETEROGENEOUS CONDITIONS
Peyman Salehi,a Mohammad Ali Zolfigol,b
and Leila Bazaz Tolamia
Department of Phytochemistry, Medicinal Plants Research
Institute, Shahid Beheshti University, Evin, Tehran, Iran;a
and Department of Chemistry, Faculty of Science, Bu-Ali Sina
University, Hamadan, Iranb
(Received December 30, 2003; accepted January 8, 2004)
1,4-Diazabicyclo[2.2.2]octane-di-N-oxide-di-perhydrate selectively ox-
idizes thiols to disulfides in acetonitrile in good yields. The method is
generally useful for a wide variety of thiols.
Keywords:
1,4-Diazabicyclo[2.2.2]octane-di-N-oxide-di-perhydrate;
disulfides; hydrogen peroxide; oxidation; thiols
Disulfides are important compounds from both synthetic and biolog-
ical viewpoints.1−3 Industrially, they find wide application as vulcan-
izing agents for rubber and elastomers, giving them excellent tensile
strength.4 The most important protocol for the preparation of disulfides
is the oxidative coupling of thiols.5 Since disulfides can be overoxidized
in the oxidation medium, selective conversion of thiols to disulfides un-
der mild conditions is important. Many reagents have been used for
this purpose.6−15
1,4-Diazabicyclo[2.2.2]octane-di-N-oxide-di-perhydrate
(DABCO-
DNODP, Figure 1) is an inexpensive, stable, and easy to handle source
of pure H2O2.16 Although I has already been synthesized and fully
We are grateful to Shahid Beheshti University Research Council for partial support
of this work.
Address correspondence to Peyman Salehi, Department of Phytochemistry, Medicinal
Plants Research Institute, Shahid Beheshti University, P.O. Box 19835-389, Evin, Tehran,
Iran. E-mail: p-salehi@ sbu.ir.
1777

1778
P. Salehi et al.
FIGURE 1 Structure of DABCO-DNODP.
characterized, unexpectedly we did not find any report on its applica-
tion in organic synthesis except our recent report on its application in
the oxidation of urazoles.17
In this article we wish to report a very efficient and simple procedure
for selective oxidation of thiols to disulfides using DABCO-DNODP un-
der heterogeneous conditions (Scheme 1).
SCHEME 1
Table I collects the results derived from the oxidation of different
kinds of thiols. The reagent was examined on a wide array of substrates,
such as aromatic (homocyclic and heterocyclic) and aliphatic (cyclic and
acyclic) thiols. As shown in Table I, coupling of aromatic thiols was
easier than coupling of aliphatic thiols.
Hydrogen peroxide and its solid complexes are usually applied in
the presence of acidic catalysts or co-oxidants; most of them are expen-
sive, corrosive, or cause environmental pollution.18−22 One of the impor-
tant advantages of this method is the application of DABCO-DNODP
without any acidic reagent. The medium is almost neutral, and acid-
sensitive groups remain intact during the course of the reaction (Table I,
entries 9, 13).
The reactions were easily carried out by stirring a mixture of thiol
and DABCO-DNODP in acetonitrile under reflux conditions. The het-
erogeneous system allowed a simple workup to be performed merely by
filtration, followed by evaporation of the solvent.
In conclusion, this is a very simple method for selective and efficient
coupling of different types of thiols. Stability and ease of handling of
the reagent, simple workup procedure, and neutrality of the reaction
medium are among the advantages that make this new method an at-
tractive addition to the previously reported procedures.

Disulfides
1779
TABLE I Oxidative Coupling of Thiols to Disulfides by
DABCO-DNODP (I) in Acetonitrile
Time
(h)
Oxid./sub.
(mole ratio)
Yielda
(%)
Entry
1
Substrate
3.5
0.8
97
2
3
1
1
0.8
0.8
95
91
4
5
1.5
1
0.8
0.8
83
93
6
5
2.5
70
7
8
CH3(CH2)6CH2-SH
CH3(CH2)10CH2-SH
5
3
2.5
2.5
70
93
9
3.5
2.5
91
10
11
HOOC CH2-CH2-SH
4
2.5
2.5
45
77
5.5
12
13
4
4
2.5
2.5
89
82
aProducts were known and identified by comparison of their
spectroscopic data (1H NMR, IR) and physical properties with
those of authentic samples.
EXPERIMENTAL SECTION
General
Products are known compounds and characterized by comparison
of their spectral data (1H-NMR, IR) and physical properties with

1780
P. Salehi et al.
authentic samples. Monitoring of the reactions was accomplished by
TLC using precoated aluminium sheets, Merck, silica gel 60 F254 (elu-
ent: MeOH/HOAc: 5/1). DABCO-DNODP was prepared according to
the reported procedure,16 and its hydrogen peroxide content was deter-
mined by titration with KMnO4.23 All yields refer to isolated products.
General Procedure for the Oxidation of Thiols
by DABCO-DNODP
DABCO-DNODP (1.6–5.0 mmol) was added to a stirred solution of
thiol (2 mmol) in acetonitrile (7 ml). The mixture was stirred magneti-
cally under reflux condition for the appropriate period of time (Table I).
Progress of the reaction was followed by TLC. The mixture was cooled
and filtered over a sintered glass funnel. Evaporation of the solvent
under reduced pressure followed by preparative thin layer chromatog-
raphy on silica gel afforded the pure products in 45–97% yield.
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