PleaseC dh oe mn oi ct a al dS cj ui es nt cme argins
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ARTICLE
Journal Name
of the required carbon-centred radical. Pathway 2 (shown in scheme extremely difficult to access under mild oxidative conditions
DOI: 10.1039/D0SC01694B
3
) on the other hand involves initial reduction of O
species capable of activating an alkyl iodide, presumably by oxidation. synthesis.
Fragmentation of the unstable I(II) species then occurs to yield the reactive species that might be promoting the reaction pathway.
2
to give a reactive and consequently are not commonly employed in organic
1
6-18
As such, we needed to consider an alternative
alkyl radical.
As the only likely reactive species capable of activating both
bromides and iodides in our solution, we suspected that the
hydroxyl radical might be fulfilling this function.
-
1.0 V
O2
Graphite
electrode
H2O
soluble
ROS
-
O2
OH
Such a pathway is appealing because the hydroxyl radical is
e
first e-
1
9, 20
known to be sufficiently reactive to activate organic halides
(
II)
HO
I
H2O
and the differing efficiencies between alkyl bromides and
iodides can be easily explained by the accessibility of the lone
pairs of the relevant halogen. Furthermore, it is known
(particularly in biological systems) that the superoxide radical
I
+
[O]
IOH +
oxidant
H
H O
second
e
2
+
-
R
R
R
R
A
(
or, since these reactions are generally performed under acidic
2
1
conditions, the hydroperoxyl radical - pKa 4.88) reacts with
hypohalous acids and hydrogen peroxide to yield hydroxyl
Scheme 3 Proposed ‘redox-relay’ ‘pathway 2’
2
2
radicals. A system therefore exists where the alkyl halide is
continually activated to form alkyl radicals via the two
interlocking cycles outlined in Scheme 4.
With regard to pathway 1, we concluded that this pathway was
unlikely to be in operation. Two observations led us to this
conclusion; Firstly, as mentioned above, cyclic voltammetry of
isopropyl iodide (see supporting information) demonstrated
that the alkyl halide is not reduced within the redox window of
the solvent so it is unlikely that superoxide (which is relatively
easily generated) will be a sufficiently powerful reducing agent
to deliver an electron to * of the C-I bond to effect homolysis.
Secondly, entry 3 in table 1 shows that water is an essential
component for successful reaction, again suggesting that more
reactive oxygen species are formed as depicted in pathway 2
R-I
O2
O2
OH
- 1.0 V
OH
I(II)
R
e
IOH
R
(Scheme 3). We also considered the possibility that under the
Scheme 4 Proposed reactive species in the redox relay pathway
acidic conditions employed, the reduction of molecular oxygen
to give hydrogen peroxide could also be occurring and therefore
this reactive oxygen species could be implicated in the process.
In order to ascertain if this was the case, we also performed the
reaction in the absence of oxygen but with hydrogen peroxide
present. No terminal product was observed in this case.
Furthermore, we also examined the addition of iron(II) sulfate
to the reaction medium in order to catalyse the formation of
hydroxyl radicals from any putative hydrogen peroxide in the
solution (the Fenton reaction) in the hope that this might
accelerate the rate of these reactions. No effect was observed
on the reaction and consequently we concluded that hydrogen
peroxide was unlikely to be a major player in the main reaction
It is noteworthy that when pure methanol (a known hydroxyl
radical scavenger) is used as the reaction solvent (Table 1,
23
entry 1), no reaction is observed until a significant amount of
water is added as a co-solvent (Table 1, entry 2). Even then, the
reaction rate is significantly attenuated, and the yield falls far
short of the optimised conditions. More detailed mechanistic
studies will follow.
1
5
An obvious question if such a redox relay pathway involving a
mutually cooperative interaction between hypohalous acid and
superoxide is the fact that hypohalous acid is not present at the
beginning of the reaction to initiate the process, how is the
reaction initiated? Given that only a trace of the hydroxyl radical
is needed to be generated before the redox relay pathway
outlined in Scheme 4 can then take over, it is possible that trace
amounts of hydrogen peroxide could be formed and then react
with superoxide in the uncatalyzed (and slow) Haber-Weiss
process, although it is possible that traces of H
O
2 2
generated via
initial reduction of aerial O
process.
2
are responsible for initiation of the
Given the observations outlined above, we believe that
pathway 2 is more likely, with the generation of the highly
reactive hydroxyl radical as the species responsible for the
reaction turnover. Initially we assumed that the iodides were
simply being oxidised to give the I(III) iodanes which then
undergo reduction to unstable I(II) species that fragment to
yield IOH and the alkyl radical. However, given that the reaction
is also applicable to some alkyl bromides (entry 7, Table 2), this
seems unlikely, since hypervalent bromine reagents are
24
reaction. Alternatively, trace amounts of iodide present in the
alkyl halide starting materials could also be responsible since
H O and iodide under acidic conditions has been suggested as
2 2
a source of hydroxyl radicals in iodine-based chemical
25
osccilators.
In order to further support the mechanistic proposal outlined in
Pathway 2 and the involvement of a transient hypervalent
4
| J. Name., 2012, 00, 1-3
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