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M. H. Ali, M. McDermott / Tetrahedron Letters 43 (2002) 6271–6273
Table 1. Oxidation of thiols 1 to disulfides 2
us a mixture of products that contained up to 45% of
dipyridyldisulfide. Allylthiol 1q failed to produce
acceptable yield of diallyldisulfide. Addition of bromine
across the double bond of allylthiol complicated the
oxidation reaction. This was not a surprise to us since
addition of bromine across carbonꢀcarbon double bond
is well documented in the literature. The most notable
feature is that we have been able to apply this proce-
dure successfully in the oxidation of dithiols to cyclic
disulfides. Large ring disulfides are difficult to synthe-
size due to competing inter molecular reaction. The
intramolecular reaction produces cyclic disulfides
whereas the intermolecular reactions yield oligomers.
Thiols (1)
Disulfide (2)
Yield
(%)a
a
b
c
d
e
f
g
h
i
Ethanethiol
Diethyldisulfide
92
99
98
97
99
95
99
98
92
97
93
87
sec-Butylthiol
Isopropylthiol
tert-Butylthiol
Butylthiol
Cyclohexylthiol
Octyllthiol
2-Hydroxyethylthiol
3-Phenylpropylthiol
Benzylthiol
Di-sec-butyldisulfide
Diisopropyldisulfide
Di-tert-butyldisulfide
Dibutyldisulfide
Dicyclohexyldisulfide
Dioctyldisulfide
Bis[2-hydroxyethyl] disulfide
Bis-3-phenylpropyldisulfide
Dibenzyldisulfide
j
k
l
Phenylthiol
Furanylthiol
Diphenyldisulfide
Difuranyldisulfide
Previously reported procedures for large ring disulfides
synthesis from dithiols produced poor to moderate
yield.12b,15 Also, most of these methods employed high
dilution techniques to avoid intermolecular reaction. In
contrast, our procedure produces excellent yields of
large ring disulfides without requiring any extra precau-
tions. We believe dispersion of dithiols over the large
surface area provided by the silica gel avoids inter-
molecular reactions. Our procedure produced excellent
yields of cyclic disulfides 2r–2w.14
m
n
o
p
q
r
s
t
u
v
w
p-Methoxyphenylthiol Bis[p-methoxyphenyl]disulfide 98
p-Chlorophenylthiol
p-Tolylthiol
2-Pyridylthiol
Bis[p-chlorophenyl]disulfide
Di-p-ditolyldisulfide
Mixture of products
Mixture of products
1,2-Dithiolane
1,2-Dithiane
trans-1,2-Dithiane-4,5-diol
1,2-Dithiepane
97
98
Allylthiol
1,3-Propanedithiol
1,4-Butanedithiol
Dithiothreitol
1,5-Pentanedithiol
1,6-Hexanedithiol
1,8-Octanedithiol
87
96
94
86
91
86
1,2-Dithiacyclooctane
1,2-Dithiacyclodecane
In conclusion, the method for oxidizing thiols with
molecular bromine on hydrated silica gel support
reported in this paper is a simple, efficient, and mild
procedure for the conversion of thiols to the disulfides
and dithiols to cyclic disulfides.
a Isolated yields.
byproduct. We postulated that the silica gel removes
the hydrogen bromides formed in the reaction, and
makes it unavailable for side reactions. We have found
that this procedure is suitable for rapid and efficient
oxidation of thiols to the disulfides (Scheme 1), and
dithiols to the disulfides (Scheme 2).
References
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This paper reports the results of the oxidation of thiols
to disulfides utilizing molecular bromine on hydrated
silica gel. The greatest advantages of this procedure
arise from its employment of non-aqueous media. The
silica gel acts as both a heat sink and as HBr scavenger.
No significant amounts of acid-catalyzed side reaction
products are found. No rise in reaction temperature is
observed. A simple filtration at the end of the reaction
followed by removal of the solvent from the filtrate
allows product isolation. High yields and high purity in
most cases indicated by both the NMR and TLC
analysis.
We have been able to oxidize a wide variety of thiols to
the corresponding disulfides in excellent yields. The
results of attempted oxidation reactions of these thiols
are presented in Table 1. Both alkyl and aryl thiols gave
similar results. As expected, sterically hindered thiols
took slightly longer time to complete the reaction com-
pared to sterically unhindered thiols. Impure products
were purified utilizing radial chromatography.
Hydroxyl, methoxy, benzylic and halogen functionali-
ties do not interfere with the oxidation of thiol group
(1h–j, 1l–o, 1t). This procedure produced good yields of
dithiols from the furfural thiol. 2-Pyridylthiol 1p gave
11. (a) Wu, X.; Rieke, R. D. Synth. Commun. 1996, 26, 191;
(b) Drabowicz, J.; Mikolajczyk, M. Synthesis 1980, 32;
(c) deLeeuw, D. L.; Musker, W. K.; Doi, J. K. J. Org.
Chem. 1982, 47, 4860; (d) Christensen, W. L.; Heacock,
D. J. Synthesis 1978, 50.