A new reagent for the efficient synthesis of disulfides from alkyl halides

Article abstract of DOI:10.1016/S0040-4039(02)02776-4

Benzyltriethylammonium tetracosathioheptamolybdate [(C₆H₅CH₂N(Et)₃)₆Mo ₇S₂₄] has been found to be a superior sulfur transfer reagent for the conversion of alkyl halides to the corresponding disulfides in excellent yields under very mild reaction conditions.

Full text of DOI:10.1016/S0040-4039(02)02776-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 887–889
A new reagent for the efficient synthesis of disulfides from
alkyl halides
Vivek Polshettiwar, Manisha Nivsarkar, Jyotiranjan Acharya and M. P. Kaushik*
Process Technology Development Division, Defence R & D Establishment, Jhansi Road, Gwalior 474002 (MP), India
Received 28 October 2002; revised 29 November 2002; accepted 6 December 2002
Abstract—Benzyltriethylammonium tetracosathioheptamolybdate [(C6H5CH2N(Et)3)6Mo7S24] has been found to be a superior
sulfur transfer reagent for the conversion of alkyl halides to the corresponding disulfides in excellent yields under very mild
reaction conditions. © 2003 Elsevier Science Ltd. All rights reserved.
Disulfides are versatile building blocks for the synthesis
of various organo-sulfur compounds,1 and they also
play important roles in biological and chemical pro-
cesses.2 Various methods have been reported in the
literature3 for the synthesis of disulfides from thiols3,4
which make use of various oxidizing agents. Oxidizing
agents ranging from molecular oxygen5 to halogens and
derivatives,6 metal oxides7 and oxo-peroxo salts8 have
been utilized to oxidize thiols to disulfides. The most
commonly used method for the direct conversion of
alkyl halides to disulfides has been by using Na2S/S.9
Nevertheless the methods currently available for the
preparation of disulfides often involve many steps and
the transformation is usually effected at 70–90°C for a
long period of time (20–30 h)9 giving only moderate
yields of the corresponding disulfide. There is current
interest in sulfur containing compounds of molybde-
num and tungsten because of their involvement in
bioinorganic chemistry and catalysis.10,11 Organic lig-
and complexes,12 thioanions13 and polymeric heteronu-
clear clusters14 formed in molybdenum–sulfur
complexes have generated interest for both synthetic
and theoretical chemists, although very few studies
have been reported on their reactivity with organic
substrates.15,16
In this communication, we report our initial findings on
the efficient sulfur transfer reaction of tetra-
cosathioheptamolybdate, MO7S246−, with alkyl halides.
The work reported17 earlier involved the use of a cation
substituted ammonium molybdate for the conversion of
alkyl halides to disulfides. Although the reagent is good
in terms of reactivity, the main disadvantage is that it is
very expensive and the starting material for its prepara-
tion is also costly and available only in research quanti-
ties. Another disadvantage is that the sulfur transfer
reaction has been performed using equimolar or a slight
excess of the reagent with respect to alkyl halide, mak-
ing the method over-all very expensive. In order to
increase the scope and utility of the suflur transfer
reagent, we have synthesized three new reagents, i.e.
[(C6H5CH2N(Et)3)6Mo7S24] (I), [(CH3(CH2)15N(Me)3)6-
Mo7S24] (II), [(C5H5N(CH2)15CH3)6Mo7S24 (III), which
were prepared from commercially available ammonium
heptamolybdate, and studied the reaction of (I) with a
variety of organic halides (1:0.183) in chloroform at
room temperature (30°C) to afford the corresponding
disulfides in excellent yields. The reactivities of the
reagents decrease in the following order [(C6-
H5CH2N(Et)3)6Mo7S24]>[(C5H5N(CH2)15CH3)6Mo7S24>
(CH3(CH2)15N(Me)3)6Mo7S24. It is evident that the
Keywords: disulfide; sulfur transfer reagent; alkyl halide.
* Corresponding author. Tel.: +91-751-2343972; fax: +91-751-2341148; e-mail: mpkaushik@rediffmail.com
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02776-4

888
V. Polshettiwar et al. / Tetrahedron Letters 44 (2003) 887–889
General procedure for the synthesis of reagent (I):
Ammonium heptamolybdate (30 g) was dissolved in
water (50 ml) and liquid ammonia (135 ml, sp.gr.0.91)
was added to give a clear solution. H2S was passed
through this solution for 5 h at 60°C. The reaction
mixture containing crystals was cooled to 0°C and
washed successively with isopropyl alcohol and ether.
The shiny dark brown crystals of ammonium tetra-
cosathioheptamolybdate were dried under vacuum.
more polarisable and more nucleophilic the reagent, the
more facile the reaction becomes.
Commercially available halides were chosen to test our
procedure. The reaction was carried out at room tem-
perature in chloroform as solvent. Under these condi-
tions, the alkyl halides were effectively and
quantitatively converted to the corresponding disulfides
proving the efficiency of the new reagent. The results of
the sulfur transfer reaction on a variety of halides with
(I) are summarized in Table 1.
To
a
solution of 32
g
of ammonium tetra-
cosathioheptamolybdate in 80 ml of water, a solution
of benzyltriethylammonium chloride in 100 ml water
was added dropwise. The reaction mixture was stirred
at room temperature for a period of 2 h. The solid that
separated was filtered, washed with isopropyl alcohol
and ether, and dried under vacuum. The dark red
Many factors such as a change in the structure of the
reagent, the halide and the structure of the alkyl group,
profoundly influence the course of the reaction. For
example, labile iodides react quickly, chlorides are
rather lethargic and fluorides do not undergo normal
reactions at all. Several investigations have been carried
out to understand the influence of structural variations
of the alkyl moiety. The reactivity order is benzyl
halide>primary alkyl halides>secondary alkyl halides>
tertiary alkyl halides>aryl halides. While benzyl halides
react faster because of the stabilization of incipient
positive charge, the non-reactivity of tertiary halides is
due to steric hindrance. The reactions of aryl halides
with the reagent do not occur favorably under these
conditions and result in poor yield of the disulfide.
crystalline
benzyltriethylammonium
tetracosathio-
heptamolybdate (mp 120°C, decomposition) was stored
in a desiccator. UV–vis (DMF); umax, 268, 323, 477.
Typical procedure for the synthesis of a disulfide: To a
solution of 1.8 mmol of reagent (I) in 35 ml of CHCl3,
10 mmol of the alkyl halide in 10 ml CHCl3 was added
dropwise over a period of 15 min. The solution was
stirred for the time shown in Table 1 at room tempera-
ture. The solvent was removed under vacuum and the
black residue was extracted with ether. The crude
product was purified by column chromatography on
silica gel to give the pure disulfide.
Thus, in this study we have been able to demonstrate
the utility and efficiency of the new sulfur transfer
reagent,
i.e.
benzyltriethylammonium
tetra-
cosathioheptamolybdate, for a new carbonꢀsulfur bond
forming reaction. In summary, the use of this reagent
offers some advantages such as easy preparation of the
reagent, economy, mild reaction conditions and a con-
venient workup procedure. Furthermore, because of its
solubility in organic solvents, this method provides a
simple, versatile and general route for the construction
of a wide variety of disulfides.
Acknowledgements
We thank Shri. K. Sekhar, Director, DRDE, Gwalior
for his keen interest and encouragement. We thank
Professor S. Chandrasekaran of the Indian Institute of
Science, Bangalore, India for helpful discussions and
also for a sample of benzyltriethylammonium tetra-
thiomolybdate. The author would like to thank Dr. D.
K. Dubey and Mr. Deepak Pardashani for the mea-
surement of mass spectra. Thanks are also to DRDO,
New Delhi for financial support to V.P.
To explore further synthetic utility of this reagent,
synthetic and mechanistic studies involving reactions of
this reagent with other organic substrates are currently
under investigation.
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