A novel method for the syntheses of symmetrical disulfides using CsF-Celite as a solid base

Article abstract of DOI:10.1016/S0040-4039(03)01402-3

The oxidative coupling of aliphatic, aromatic and heteroaromatic thiols to disulfides using cesium fluoride-Celite is described. CsF-Celite provides an efficient, convenient and practical method for the syntheses of symmetrical disulfides.

Full text of DOI:10.1016/S0040-4039(03)01402-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6789–6791
A novel method for the syntheses of symmetrical disulfides using
CsF–Celite as a solid base
a
b
a
a,
Syed Tasadaque A. Shah, Khalid M. Khan, Miriam Fecker and Wolfgang Voelter *
a
Abteilung f u¨ r Physikalische Biochemie des Physiologisch-chemischen Instituts der Universit a¨ t T u¨ bingen, Hoppe-Seyler Straße 4,
D-72076 T u¨ bingen, Germany
b
HEJ Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270,
Pakistan
Received 19 February 2003; revised 5 March 2003; accepted 5 June 2003
Dedicated to Professor Atta-ur-Rahman on the occasion of his 60th birthday
Abstract—The oxidative coupling of aliphatic, aromatic and heteroaromatic thiols to disulfides using cesium fluoride–Celite is
described. CsF–Celite provides an efficient, convenient and practical method for the syntheses of symmetrical disulfides.
©
2003 Elsevier Ltd. All rights reserved.
1
,2
Disulfides are useful reagents in organic synthesis.
explored its utility by preparing disulfides using similar
reaction conditions. Moreover, importance of the
fluoride ion as a catalyst for the promotion of various
types of base-catalyzed reactions in organic synthesis
Disulfides are also used in sulphenylation of enolates
and other anions, and they are essential moieties of
biologically active compounds for peptide and protein
stabilization. As disulfides are relatively more stable to
3
4
16
has been previously recognized. In particular the work
organic reactions such as oxidation, alkylation and
acylation compared to the corresponding free thiols, the
thiol group can conveniently be protected as a disulfide.
The desired thiol can be generated from the disulfide
either by reduction or by other sulfurꢀsulfur bond
5
of Clark and Miller revealed that the fluoride ion has
an effect on coupling reactions because of its high
17
capability of hydrogen bond formation. As reagents
for generating the fluoride ion in these reactions, potas-
sium, cesium and tetraalkylammonium fluorides were
generally used so far. However, it is not easy to handle
these hygroscopic reagents and the reproducibility of
these reactions are invariably poor. Previously, poorly
hygroscopic reagents generating fluoride ions were
designed by allowing cesium fluoride to be absorbed on
−
−
cleavage reactions such as CN , OH or hydrazines.
Various reagents for oxidative coupling of thiols to6
disulfides are described, e.g. iodine/hydrogen iodide,
7
8
9
neat bromine, FeCl /NaI, KMnO /CuSO
and
hydrogen peroxide in tetrafluoroethanol. Further-
3
4
4
1
0
11
18
more, some of the non-metallic reagents like Br ,
DMSO also accomplish thiol coupling, but they
encounter the difficulty of product handling and isola-
tion. Enzymatic and electrochemical methods are
also known to perform this oxidative transformation.
However, there is still an interest in developing a clean,
mild and efficient method to synthesize aliphatic, aro-
matic and heteroaromatic disulfides.
Celite. The effect of cesium fluoride–Celite might be
2
1
2
twofold: (a) activation of thiol groups by the fluoride
ion, whose ionic character is increased owing to the low
charge/surface area ratio of the cesium cation and (b)
activation of the alkyl group by a Lewis acid type
1
3
14
19
effect.
The present method (Scheme 1) is equally applicable
for the oxidative coupling of alkyl, aryl and hetero-
cyclic thiols, and the efficiency of the procedure is also
In connection with our current studies on the synthesis
15
of ethers, esters, thioethers and thioesters
using
cesium fluoride–Celite as a solid base, we further
*
0
Corresponding
wolfgang.voelter@uni-tuebingen.de
author.
Fax:
+497071-293348;
e-mail:
Scheme 1.
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01402-3

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S. T. A. Shah et al. / Tetrahedron Letters 44 (2003) 6789–6791
Table 1. Synthesis of disulfides using CsF–Celite
Table 2. Synthesis of cyclic tetrasulfides using CsF–Celite
demonstrated by coupling of long chain thiols (entries
ent spectroscopic techniques and their elemental
analyses.
1
–3). We have noticed that the coupling of dithiol
compounds resulted in the formation of cyclic tetra-
sulfide products (compounds 12 and 13).
In conclusion, CsF–Celite-assisted reactions provide an
easy access for the syntheses of disulfides in good
yields. As this methodology has several advantages, it is
a valuable addition to existing methods. In short this is
an efficient, convenient, inexpensive, non-corrosive and
practical method for preparing symmetrical disulfides.
The reactions catalyzed by cesium fluoride–Celite are
usually carried out under mild conditions with good
yields and simple workup: Only filtration is required to
remove the catalyst and often evaporation of the filtrate
afforded pure products. We explored the utility of the
CsF–Celite system as an efficient, inexpensive and non-
corrosive reagent for the synthesis of disulfides and
cyclic tetrasulfides, depending upon the substrate used.
Several examples of CsF–Celite-assisted couplings of
aliphatic, aromatic and heteroaromatic thiols into
disulfides are presented in Tables 1 and 2.
Acknowledgements
We express our gratitude to Deutscher Akademischer
Austauschdienst (DAAD, Bonn, Germany) for a sand-
wich-type scholarship, granted to Syed Tasadaque Ali
Shah.
In a typical reaction, a mixture of thiol (1.0 mol),
CsF–Celite (1.5 mol) in acetonitrile is stirred at room
temperature or under reflux and access to atmospheric/
oxygen. The completion of reaction is monitored by
TLC. After completion of the reaction, the reaction
mixture is filtered and the filtrate evaporated to afford
the pure product. The physical properties and NMR
spectra of compounds agreed with those reported in the
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