OXIDATION OF THIOLS TO

DISULFIDES WITH
MOLECULAR BROMINE ON
HYDRATED SILICA GEL
SUPPORT

Mohammed Hashmat Ali*, J. Mario
McDermott
Chemistry Department
Southeast Missouri State University
Cape Girardeau, Missouri 63701.


Reaction Scheme





RSH
Hydrated Silica gel,
Methylene chloride
Bromine
RSSR
SH
SH
S
S
Hydrated Silica gel,
Methylene chloride
Bromine
Introduction
We have developed a procedure for oxidation
of thiols to disulfides with moleculer bromine
on hydrated silica gel support. This procedure
is simple, highly efficient, and very selective.
Presence of a base to neutralize the hydrogen
bromide formed in the reaction is not
necessary. A variety of thiols can be oxidized
to the corresponding disulfides. Cyclic
disulfides of various ring size can also be
easily prepared from dithiols utilizing this
procedure.

Oxidation of Thiols to Disulfides with Molecular Bromine
CH
3
(CH
2
)
6
CH
2
S-SCH
2
(CH
2
)
6
CH
3
HOCH
2
CH
2
SH
CH
3
(CH
2
)
6
CH
2
SH
CH
3
CH
2
CH
2
CH
2
S-SCH
2
CH
2
CH
2
CH
3
HOCH
2
CH
2
S-SCH
2
CH
2
OH
CH
3
CH
2
CHCH
3
SH
CH
3
CH
2
CHCH
3
S-SCH
3
CHCH
2
CH
3
CH
3
CH
2
CH
2
CH
2
SH
100%
100%
98%
100%

(CH
3
)
3
CSH
(CH
3
)
3
CS-SC(CH
3
)
3
CH
3
CH
2
SH
CH
3
CH
2
S-SCH
2
CH
3
(CH
3
)
2
CHSH
(CH
3
)
2
CHS-SCH(CH
3
)
2
97%
98%
98%
PhCH
2
S-SCH
2
Ph
PhCH
2
SH
97%
PhCH
2
CH
2
CH
2
SH
92%
Ph(CH
2
)
2
CH
2
S-SCH
2
(CH
2
)
2
Ph
S H
3
C S CH
3
SH CH
3
O
S CH
3
O S OCH
3
SH Cl
S Cl S Cl
SH
SH
S
S
100%
100%
97%
100%
SH CH
3
94%
SH
S
S
SH
SH
HO
S
S
HO
HO
O
SH
HO
95%
O
S O
S
SH
SH
S
S
86%
SH
SH
S
S
89%
91%
SH
S
S
SH
Experimental Procedure
The following procedure is general for the
reported reactions.
2.5 mL of water was added dropwise to a 5 gm of
silica gel with stirring. Stirring continued until a
free flowing solid was obtained. 25 mL of
methylene chloride was added to the flask
followed by the addition of 2-3 mmole of the
thiol under investigation. A solution of bromine
on methylene chloride was added drop by drop
until a faint orange color persisted or TLC
indicated the complete disappearance of the
starting thiol. The reaction mixture was
then filtered and the solid was washed with
about 75-80 mL of methylene chloride.
Removal of the solvent from the filtrate
produced the disulfide product which was
often pure by NMR and TLC. Impure
products were purified by radial
chromatography.

Advantages of Hydrated Silica Gel
Support

Organic solvents can be employed
in the reactions which previously
required aqueous media.

Activates reagents by dispersing
active sites.

Simplifies work-up of the reaction.
Eliminates or reduces exposure to
toxic reagents.

Produces easy-to-handle solid
waste.

Generates smaller amounts of
waste.

Conclusions:

The procedure described has the
following desirable qualities:

Employs non-aqueous media.

Simple procedure.


Presence of a base is not required
to neutralize the hydrogen bromide
formed in order to prevent side
reactions. Hydrogen bromides are
absorbed on the silica gel and are
removed from the reaction.


Excellent efficiency.

Highly selective.

Work-up is trivial.

Environmentally benign.



Grants and Research Funding Committee
Chemistry Department
Southeast Missouri State University
Cape Girardeau, Missouri 63701
Acknowledgment

Southeast Missouri State University
Southeast Missouri State University