Mechanism of Oxidation of a Thioether by Oxyiodine Species
633
well known bioactive molecule.[19,31–33] The overall stoichiom-
etry of this reaction (Eqn 4) introduces iodide ions into the
reaction medium. Iodide is known to form an equilibrium
mixture with aqueous iodine to form triiodide:[34,35]
accumulation of iodide and subsequent formation of iodine.
We can represent NAM as RSCH3, a methyl thioether.
HIO3 þ RSCH3 ! HIO2 þ RSOCH3
HIO2 þ RSCH3 ! HOI þ RSOCH3
HOI þ RSCH3 ! Hþ þ Iꢀ þ RSOCH3
ð20Þ
ð21Þ
ð22Þ
ꢀ
I2 þ Iꢀ
I
ð17Þ
!
3
Initial attack (Eqn 14) is an electrophilic attack by molecular
iodine. Triiodide, on the other hand, is a nucleophile and would
undergo Eqn 14 at a much slower rate than molecular iodine.
This will inhibit the reaction, and this inhibition intensifies as
the reaction proceeds and more iodide is formed. If one assumes,
in the extreme case, that triiodide is inert, then the rate of the
I2–NAM reaction is given by:
Accumulation of I– from Eqns 20–22 then transfers the rate-
determining step to Eqn 23:
IOꢀ3 þ Hþ þ Iꢀ HIO þ HOI
ð23Þ
!
2
Eqn 23 is the initiation reaction for the Dushman reaction in
low iodide conditions, with iodine subsequently generated in a
single reaction:[36]
k2½I2ꢃ ½NAMꢃ
1 þ0Keq½Iꢀꢃ 0
rate ¼
ð18Þ
HOI þ Iꢀ þ Hþ ! I2 þ H2O
ð24Þ
The ‘0’ subscripts denote initial concentrations. One can
re-write Eqn 18 in a linear form as follows:
Reduction of iodine by NAM (Eqn 4) generates iodide which
inhibits its further reduction, but catalyzes the reaction that
forms iodine (Eqn 23). Coupled with the protonation of the
sulfur centre, this explains the almost instant iodine formation
observed.
1
1
Keq½Iꢀꢃ0
¼
þ
ð19Þ
rate k2½I2ꢃ0½NAMꢃ0 k2½I2ꢃ0½NAMꢃ0
A plot of the modulus of the inverse of the rate versus added
iodide concentration should give a straight line that should
deliver a value of k2 from the intercept and a value for Keq, if
indeed I–3 was inert. The slope of the plot should deliver the
bimolecular rate constant between iodine and NAM. In the limit
of high initial iodide concentrations, the second term in Eqn 19
dominates. With no iodide ions initially added to the reaction
mixture, Eqn 19 reverts to a pure bimolecular reaction that
should deliver a value for k2. This value can be checked against
the one generated from the initial rate data from Figs 10 and 11.
This treatment deduced k2 to be 5.65 Mꢀ1 sꢀ1. This value is not
very different from that determined from the initial rate studies
of 5.23 Mꢀ1 sꢀ1. If we assume this rate constant, we can utilise
the slope of the graph to determine the Keq of the I2/I–3 equili-
brium. If the value determined is lower than the literature
value[34] of 770 Mꢀ1, this would indicate that I–3 is not totally
inert, and does contribute, albeit at a lower effective rate.
A sharp slope in the plot indicates a strong iodide effect and a
larger discrepancy in the reactivities of I2 versus I–3. The plot in
Fig. 13 deduced a value of Keq ¼ 478 Mꢀ1 (no error bars
available for this value, unless several iodide dependence plots
had been performed at various combinations of initial reagent
concentrations). This deduced value for Keq indicates a strong
contribution to oxidation of NAM from I–3.
Reaction Modelling
The whole reaction scheme is compiled in the reactions shown
in Table 1. It is a simple 11-reaction scheme that does not
assume complete inertness of the triiodide (the discrepancy in
Keq values obtained from our experimental data and literature
values indicates some activity by triiodide), but the assumed
rate constant was much less than that assumed for aqueous
iodine. The first five reactions are standard iodine and oxyiodine
reactions, and their kinetics values were sourced from literature
values.[22,27–29] Reaction M6, the association/dissociation of
iodic acid, was derived from silver iodate solubility studies
of Naidich and Ricci.[37] Although a dissociation constant for
HIO3 of 0.163 was derived, it was not easy to extrapolate to our
conditions (pH and ionic strength). Work by Li and Lo[38]
deduced a slightly lower value of 0.154, but values as high as
0.470 have also been reported.[39] However, since it is a pro-
tolytic process, reaction rates were assumed to be nearly diffu-
sion-controlled, in both directions, while adhering to the acid
dissociation constant.
Reactions M7–M9 represent the initiation cascade of reac-
tions needed to generate the reactive species through accumu-
lation of iodide. The normally believed theory that iodate
solutions always have high enough iodide concentrations,
,10ꢀ6 M, to initiate Eqn 23 could not explain the almost instant
production of iodine a few seconds after mixing reaction
solutions. Thus, in simulating the global reaction dynamics,
the most important kinetics parameter is kM7; the initiation
reaction that starts the iodide formation cascade. The value
adopted for this parameter determined the rate of formation of
aqueous iodine. Kinetic parameters for reactions M8 and M9 are
not relevant for as long as they are faster than the rate constant
for M7. Reactions M9 and M10 involve oxidation of NAM by
HOI and I2 respectively. Reaction M9 involves an oxygen atom
transfer while M10 is an electrophilic attack followed by a
hydrolysis. In this mechanism, we made kM9 . kM10. Overall,
this did not affect the simulations because of the low HOI
Overall Reaction Dynamics
The reaction of molecular iodine with NAM is sluggish enough
such that it is unable to mop up all the iodine generated through
the Dushman reaction. Hence iodine formation commences
almost as soon as acidic iodate and NAM are mixed together.
Iodate is inert in low acid environments. Highly acidic envir-
onments inhibit Eqn 14, the direct reaction between NAM and
I2, by protonating the nucleophilic sulfur centre of the thioether.
The reaction initiation itself, in the absence of added iodide, is
through a general reaction of iodic acid with the thioether,
generating a cascade of reactive oxyiodine species which will
promote the reaction’s progress. One can write the following
series of reactions (Eqns 20–22), which lead to the initial