Chemistry Reference
In-Depth Information
O
N
NH
2
N
1) H
2
O
2
/ I
2
2) NaOH
N
NH
2
N
Fig. 11.39
Aromatisation of a
heterocyclic intermediate.
biggest current industrial use of H
2
O
2
in sulfur oxi-
dation, many of the products being used as rubber
vulcanisation accelerators and other chemical inter-
mediates. Tetraalkyl thiuram disulfides are a good
example [275] (Fig. 11.42). The reaction can be
carried out under either acidic or alkaline conditions,
but the latter are chosen because of the ease of
separation of the hydrophobic product from the
thiol, which is in solution as its anion. Careful
control of pH is necessary to avoid side reactions.
Hydrogen peroxide and sodium hypochlorite are
both used industrially at present for these oxidations,
but catalysed air oxidation methods are now avail-
able and are likely to become more widespread in
the future.
There are still, however, new reports of the use of
H
2
O
2
for this reaction. A process has been patented
[276] for the manufacture of dimethyl disulfide by
reacting 70% H
2
O
2
and sodium methanethiolate
under reduced pressure, such that the product
vaporises and is then distilled and recovered. In
another patent [277], dithiodipropionic acid is pre-
pared from 2-thiopropionic acid with H
2
O
2
at 50°C
without catalyst.
Exhaustive oxidation of thiols to sulfonic acids can
be carried out by Fenton's reagent [278] or by other
catalysed H
2
O
2
systems, including phosphotungstic
acid on alumina [272], which gives 94% yield of
benzenesulfonic acid from thiophenol in 45 min at
80°C. Simple homogeneous tungstate catalysis also
can be effective, e.g. in preparing isethionic acid from
2-thioethanol [279] (Fig. 11.43).
O
[O]
[O]
S
S
O
S
O
Sulphoxide
Sulphone
Fig. 11.40
Oxidation of sulfides.
It has been found recently [269] that sulfide oxi-
dation, like tertiary amine oxidation, can be catal-
ysed by bicarbonate: ethyl phenyl sulfide is oxidised
primarily to sulfoxide, with some sulfone at higher
molar ratios, in water/ethanol or /
t
-butanol mix-
tures. The study was used in part to model the deto-
xification of mustard gas (bis-2-chloroethyl sulfide)
and related chemical warfare agents. This application
has driven studies on molybdate- and tungstate-
doped porous carbons for sulfide oxidation [270].
Reactive sulfides can be oxidised to sulfoxides
using peroxynitrous acid generated in situ from
nitrous acid and H
2
O
2
[271]. The oxidant system
decomposes rapidly and a relatively low H
2
O
2
effi-
ciency is to be expected for many substrates.
Oxidation of penicillins to sulfoxides, although on
a relatively small scale, is an important intermediate
reaction in cephalosporin manufacture. This has
been performed traditionally with peracetic acid on
a stoichiometric basis. A catalytic system using H
2
O
2
and phosphotungstic acid on alumina has been dis-
closed [272].
Dimethyl sulfoxide can be oxidised to the sulfones
using H
2
O
2
and TS-1 [273].
S-S Oxidations
By careful choice of oxidant and conditions it is pos-
sible to access many of the intermediates shown on
the thiol oxidation scheme, although some are fairly
unstable to reactions such as disproportionation, as
shown.
Thiol oxidations
The oxidation scheme for thiols is quite complex
(Fig. 11.41). The first stage is always the formation
of disulfides (S-S coupling), and this represents the
