Laleve´e et al.
ROO• + ArO• f non-radical products (very fast) (6)
inhibited rate ) (-d[O2] ⁄ dt)inh ) kp[RH]Ri ⁄ 2kinh[ArOH]
(II)
[OCH(Ph)CH2O]nO• + CH2 ) CHPh f
[OCH(Ph)CH2O]nOCH2C(•)HPh (3′)
The absence of a hydroperoxide, ROOH, in this autoxidation
greatly aided the discovery9 that deuterated phenols, ArOD, were
much poorer antioxidants than their protic partners, ArOH, as
would be expected for the inhibition process delineated by
reactions 5 and 6. The existence of a substantial deuterium
It will be obvious that the greater the absolute magnitude of
kinh the more effective will be the antioxidant. Nature’s principle
lipid-soluble chain-breaking antioxidant, R-tocopherol (vitamin
E), has a greater kinh value than all common commercial phenolic
antioxidants.3e Nevertheless, there have been a number of
successful attempts to outdo Nature with rational syntheses of
phenols having greater kinh values than R-tocopherol,3e,4,5 and
today the largest kinh values approach the diffusion-controlled
limit.5c
Since the retardation of oxidative degradation is vital to life
and commerce, there is a growing acknowledgment of the
importance of having reliable rate constants both for propaga-
tion, kp, and inhibition, kinh. Surprisingly, however, the vast
majority of kp values for single organic compounds of known
structure (e.g., olefins, alkylaromatics, ethers, etc) were deter-
mined over 40 years ago by the rotating sector (RS) technique.6,7
The RS method can be applied to chain reactions in which the
termination step involves a bimolecular reaction between two
of the chain carrying radicals,6–8 e. g., reaction 4, and it is the
rate constant for this step, 2kt, that is actually determined. Values
of kp must then be calculated from the measured rate of the
uninhibited reaction at a predetermined rate of initiation, Ri,
equation I.6–8 Values of kinh can only then be obtained from
measured inhibited reaction rates at known Ri via equation II.
Furthermore, equation II only applies if the inhibited reaction
is still a chain (chain length >5) so that reactions 2 and 5 are
in competition for the available chain-carrying radicals.
9
H
kinetic isotope effect, k5 /k5D ) ∼10.6, had not previously been
recognized because of deuterium exchange between the added
ArOD and the much larger quantity of ROOH formed in the
inhibited autoxidation of most organic substrates. The RS
method demonstrated that styrene had a fairly large propagation
rate constant (kp303K ) 41 M-1 s-1)6 compared with most other
303K
readily oxidized hydrocarbons, such as cumene, kp
) 0.18
M-1 s-1,7 and tetralin, kp303K ) 6.4 M-1 s-1.7 This means that
it is easier to have an inhibited autoxidation of styrene occurring
via a chain reaction (essential for the determination of kinh via
eq II) than is the case for the inhibited autoxidation of most
other substrates.
A very large number of phenol kinh values, indeed the
majority, are based on measurements of the rates of inhibited
autoxidation of styrene, the IAS method.3e,4,5 This procedure
appears to be the method of choice for even the very strong-
est antioxidants (high kinh) for both phenols5c,d and aromatic
amines.11 However, this large body of antioxidant data is based
on a single RS study of the uninhibited autoxidation of styrene,6
and the reliability of these IAS-derived kinh values has received
only a few independent checks.12 This is a matter for concern,
a concern that is reinforced by the recent use of the IAS-derived
value of kinh for R-tocopherol to calculate rate constants for some
fast unimolecular peroxyl radical reactions, i.e., to calibrate some
peroxyl radical “clocks”.13 The RS method yields reliable rate
constants when chain termination occurs with strictly second-
order kinetics,8 as is the case for the autoxidation of almost all
pure hydrocarbons,7 i.e., -d[O2]/dt ) C Ri1/2. However, this is
not the case for styrene, for which -d[O2]/dt ) C Rin with 1.0
> n > 0.5.6 The greater than 0.5 order in Ri indicates that the
usual second-order, ROO• + ROO• chain termination, reaction
4, is accompanied by a kinetically first-order chain termination
process, ROO• + X f non-radical products. The need to
“correct” for the first-order component of termination in the
autoxidation of styrene in order to determine the value of 2kt,
and hence kp, brings into question the reliability of both of these
rate constants, and this, in turn, brings into question the
reliability of all the absolute (not relative) kinh values determined
by the IAS method.
For reasons connected with the (then unknown) mechanism
by which phenols retarded the rates of autoxidation of organic
liquids, the substrate selected for the determination of kinh values
was styrene.9 This compound was chosen because the rate
controlling propagation step (kp) involves the addition of a
poly(peroxystyryl)peroxyl radical to a styrene molecule,10
reaction 3′.
(3) (a) Burton, G. W.; Joyce, A.; Ingold, K. U. Lancet 1982, 327 August.
(b) Burton, G. W.; Joyce, A.; Ingold, K. U. Arch. Biochem. Biophys. 1983, 221,
281–290. (c) Burton, G. W.; Ingold, K. U. Acc. Chem. Res. 1986, 19, 194–201.
(d) Ingold, K. U.; Webb, A. C.; Witter, D.; Burton, G. W.; Metcalf, T. A.; Muller,
D. P. R. Arch. Biochem. Biophys. 1987, 259, 224–225. (e) Burton, G. W.; Doba,
T.; Gabe, E. J.; Hughes, L.; Lee, F. L.; Prasad, L.; Ingold, K. U. J. Am. Chem.
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105, 5950–5951. (b) Barclay, L. R. C.; Vinqvist, M. R.; Mukai, K.; Itoh, S.;
Morimoto, H. J. Org. Chem. 1993, 58, 7416–7420. (c) Foti, M. C.; Johnson,
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(5) (a) Pratt, D. A.; DiLabio, G. A.; Brigati, G.; Pedulli, G. F.; Valgimigli,
L. J. Am. Chem. Soc. 2001, 123, 4625–4626. (b) Valgimigli, L.; Brigati, G.;
Pedulli, G. F.; DiLabio, G. A.; Mastragostino, M.; Arbizzani, C.; Pratt, D. A.
Chem. Eur. J. 2003, 9, 4997–5010. (c) Wijtmans, M.; Pratt, D. A.; Valgimigli,
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corrigendum, 4847. (d) Wijtmans, M.; Pratt, D. A.; Brinkhorst, J.; Serwa, R.;
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During kinetic studies on the addition of R-aminoalkyl
radicals to acrylates,14a–c the exciting discovery was made that
(12) The main procedure employed to check the IAS-derived values of kinh
has been the EPR method with the Me3COO• radical.3e For R-tocopherol the
IAS-derived values of kinh have also been checked using the LFP-generated
cumylperoxyl radical and monitoring the grow-in of the tocopheroxyl radical,
see: Valgimigli, L.; Banks, J. T.; Lusztyk, J.; Ingold, K. U. J. Org. Chem. 1999,
64, 3381–3383, The value of kinh for R-tocopherol is particularly important since
it has been used to “anchor” and calibrate a number of newly developed peroxyl
radical clocks.13
(13) Tallman, K. A.; Pratt, D. A.; Porter, N. A. J. Am. Chem. Soc. 2001,
123, 11827–11828. Roschek, B., Jr.; Tallman, K. A.; Rector, C. L.; Gillmore,
J. G.; Pratt, D. A.; Punta, C.; Porter, N. A. J. Org. Chem. 2006, 71, 3527–3532.
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