Oxidative decarboxylation of 4-methoxyphenylacetic acid induced by potassium 12-tungstocobalt(III)ate. The role of intramolecular electron transfer

Article abstract of DOI:10.1039/b200388k

A kinetic study of the oxidation of 4-methoxyphenylacetic acid (AnCH₂CO₂H: An = 4-MeOC₆H₄) with potassium 12-tungstocobalt(III)ate (K₅[Co^IIIW₁₂O₄₀] ≡ Co^IIIW) has been carried out in aqueous solution at different pH values (between 2.15 and 4.98). The reaction proceeds via a rate determining electron transfer, followed by a fast decarboxylation step leading to a 4-methoxybenzyl radical. From the analysis of the kinetic data the rate constants for reaction of Co^IIIW with AnCH₂CO₂H and AnCH₂CO₂^- respectively, k₁ and k₂, have been derived as k₁ = 0.109 M^-1 s^-1 and k₂ = 2.948 M^-1 s^-1, indicating that in the oxidation of 4-methoxyphenylacetic acid by Co^IIIW, ionization of the carboxylic group results in an almost 30-fold acceleration of the decarboxylation rate. In order to explain this behavior, it is proposed that no aromatic radical cation is formed as a reaction intermediate, electron removal from the aromatic ring being instead concerted with an intramolecular side-chain to nucleus electron transfer, directly leading to a carboxyl radical which then undergoes rapid decarboxylation to give the 4-methoxybenzyl radical.

Full text of DOI:10.1039/b200388k

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Oxidative decarboxylation of 4-methoxyphenylacetic acid induced
by potassium 12-tungstocobalt(III)ate. The role of intramolecular
electron transfer
a
b
2
Enrico Baciocchi* and Massimo Bietti*
a
Dipartimento di Chimica, Università “La Sapienza”, P. le A. Moro, 5 I-00185 Rome, Italy
Dipartimento di Scienze e Tecnologie Chimiche, Università “Tor Vergata”,
Via della Ricerca Scientifica, I-00133 Rome, Italy
b
Received (in Cambridge, UK) 11th January 2002, Accepted 26th February 2002
First published as an Advance Article on the web 12th March 2002
A kinetic study of the oxidation of 4-methoxyphenylacetic acid (AnCH CO H: An = 4-MeOC H ) with potassium
2-tungstocobalt()ate (K [Co W O ] ≡ Co W) has been carried out in aqueous solution at different pH values
between 2.15 and 4.98). The reaction proceeds via a rate determining electron transfer, followed by a fast
2
2
6
4



1
5 12 40
(
decarboxylation step leading to a 4-methoxybenzyl radical. From the analysis of the kinetic data the rate constants


Ϫ
2
for reaction of Co W with AnCH CO H and AnCH CO respectively, k and k , have been derived as k = 0.109
2
2
2
1
2
1
Ϫ1 Ϫ1
Ϫ1 Ϫ1

M
s
and k = 2.948 M s , indicating that in the oxidation of 4-methoxyphenylacetic acid by Co W, ionization
2
of the carboxylic group results in an almost 30-fold acceleration of the decarboxylation rate. In order to explain this
behavior, it is proposed that no aromatic radical cation is formed as a reaction intermediate, electron removal from
the aromatic ring being instead concerted with an intramolecular side-chain to nucleus electron transfer, directly
leading to a carboxyl radical which then undergoes rapid decarboxylation to give the 4-methoxybenzyl radical.
The oxidative decarboxylation of arylalkanoic acids is an
where the carboxylate anion predominates and an upper limit
7 Ϫ1
1,2
important reaction both in chemistry and biology. As an
example, most non-steroidal anti-inflammatory drugs have
an α-arylacetic or an α-arylpropionic acid structure, and it is
possible that these drugs are metabolized via an oxidative
for decarboxylation (kdec ≥ 5 × 10 s ) was established. How-
ever, no evidence for the formation of an intermediate radical
cation was provided.
More recently Kochi studied the decarboxylation of aryl-
acetates by photoinduced electron transfer in charge transfer
ion pairs between arylacetate anions and a cationic acceptor in
aqueous solution, providing absolute rates of decarboxylation:
3
decarboxylation pathway. Moreover, many drugs, herbicides
and pesticides containing a carboxylic group can produce via
2
decarboxylation potentially toxic radical intermediates.
9
Ϫ1 8
The oxidative decarboxylation of arylacetic acids by cobaltic
kdec ≈ 10 s . Also in this case, no evidence for the involvement
4
5
acetate, ceric ammonium nitrate (CAN) and potassium 12-
of aromatic radical cations was provided.

tungstocobalt()ate (K [Co W O ], from now on indicated as
In this context, several questions concerning the mechanism
of the oxidative decarboxylation of arylacetic acids remain
unanswered. Apart from the fact that there is no clear evidence
for the involvement of aromatic radical cations, another aspect
of interest is whether decarboxylation occurs directly from the
radical cation or from an intermediate acyloxyl radical, as
5
12 40


6
Co W) as the oxidants has been kinetically investigated using
the competitive method. A mechanism involving a direct inter-
action between the carboxylic group and the metal complex was
suggested, but it was also proposed that in the presence of elec-
tron releasing ring substituents, like a para-methoxy group, an
electron transfer mechanism could operate (Scheme 1).
9
clearly shown in the case of benzoic acids. The acyloxyl
radical, in turn, might be formed directly or following intra-
molecular electron transfer in an intermediate radical cation.
In order to obtain more information about this complex
mechanistic picture, we have carried out a kinetic study, at dif-
ferent pH values, of the oxidation of 4-methoxyphenylacetic
acid (AnCH CO H: An = 4-MeOC H ) with the well known
2
2
6
4


10,11
outer sphere one-electron oxidant Co W.
By this study it
has been possible to determine the reaction rate for both the
neutral and ionized form of 4-methoxyphenylacetic acid and to
get a further insight into the reaction mechanism.
Scheme 1
The formation of an intermediate aromatic radical cation,
which then undergoes rapid decarboxylation leading to a benz-
ylic radical was also the conclusion of Steenken and Gilbert
Results and discussion
The oxidation of AnCH CO H by Co W has been studied in
2 2
water at T = 20 ЊC. Product analysis has shown the formation
of 4-methoxybenzyl alcohol as the exclusive product.
kinetic study of the reaction has been carried out spectro-
photometrically, following the decrease in absorbance of Co W
at 390 nm. The pH has been varied between 2.15 and 4.98 using
a NaOH–citric acid buffer, and the ionic strength of the sol-


who studied the oxidative decarboxylation of 4-methyl- and
7
4
-methoxyphenylacetic acids by laser flash photolysis. Lower
6,12
limits for the decarboxylation rate of 4-methylphenylacetic acid
The
7
Ϫ1
were provided (kdec > 10 s ), following the formation of the
-methylbenzyl radical, and it was also shown that the rate

4
constant increases with increasing pH, indicating that decarb-
oxylation is faster when the carboxyl group is ionized. 4-
Methoxyphenylacetic acid was studied only under conditions
ution has been buffered with NaClO . From the analysis of the
4
7
20
J. Chem. Soc., Perkin Trans. 2, 2002, 720–722
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b200388k

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

Table 1 kobs values for the Co W induced oxidation of 4-methoxy-
phenylacetic acid in water at T = 20 ЊC at pH = 2.58 and 4.50
From the equilibrium constant for the dissociation of
Ϫ ϩ
4
-methoxyphenylacetic acid: K = [AnCH CO ][H ]/[AnCH -
a
2
2
2
CO H] we obtain:


Ϫ1 a
2
pH
[Co W]/M
kobs/s
Ϫ
2
ϩ
kobs/[AnCH CO ] = 2(k ϩ k [H ]/K )
(5)
Ϫ3
2
2
1
a
2
.58
0.0005
6.6 × 10
Ϫ3 b
Ϫ3
6
.4 × 10
Ϫ
which predicts a linear correlation between k /[AnCH CO ]
2
2
.58
.58
0.001
0.0015
6.4 × 10
7.1 × 10
obs
2
2
Ϫ3
ϩ
and [H ], with 2k
/K as the slope and 2k as the intercept.
1 a 2
Ϫ ϩ
Ϫ3 b
Ϫ2
6
.0 × 10
By plotting kobs/[AnCH CO ] against [H ] a very good linear
2
2
4
4
.50
.50
0.0003
0.0005
6.3 × 10
correlation is indeed observed (Fig. 1), and given that K =
a
Ϫ2 b
Ϫ2
6
.5 × 10
6.4 × 10
Ϫ2 b
Ϫ2
6
.2 × 10
4
4
.50
.50
0.001
0.0015
6.5 × 10
6.7 × 10
Ϫ2
Ϫ2 b
6
.0 × 10
a
Measured as described in eqn. (1). Each value is the average of 3–5
b
experiments: error ≤ 5%. Reaction carried out in the presence of
Co W.


Table 2 kobs values for the Co W induced oxidation of 4-methoxy-
phenylacetic acid in water at T = 20 ЊC at different pH values
Ϫ1 a
pH
kobs/s
Ϫ3
Ϫ3
Ϫ2
Ϫ2
Ϫ2
Ϫ2
Ϫ2
2
2
3
3
4
4
4
.15
5.0 × 10
6.4 × 10
1.0 × 10
2.1 × 10
3.8 × 10
6.5 × 10
8.6 × 10
.58
.04
.59
.03
.50
.98
Ϫ
ϩ
Fig. 1 Plot of the kobs/[AnCH
CO
] ratio vs. concentration of H
2
2

for the reactions of 4-methoxyphenylacetic acid with Co W in H
(NaOH–citric acid buffer) at T = 20 ЊC. r = 0.998.
O
2
2
Ϫ5
14,15
4.36 × 10 M,
from the slope and intercept, the rate constants
 Ϫ
for reaction of Co W with AnCH CO H and AnCH CO
respectively, k and k , can be derived.
The values thus obtained: k = 0.109 M
a
Measured as described in eqn. (1). Each value is the average of 3–5
2
2
2
2
experiments: error ≤ 5%.
1
2
Ϫ1
Ϫ1
s
and k2 =
1
Ϫ1 Ϫ1
2
.948 M s , indicate that in the oxidation of 4-methoxy-

phenylacetic acid by Co W, ionization of the carboxylic group
results in an almost 30-fold acceleration of the decarboxylation
rate.
At first sight, these kinetic results might be interpreted on the
basis of the generally accepted mechanism for the oxidative
decarboxylation of electron rich phenylacetic acids (Scheme 2),
kinetic data a second order equation is obtained showing that,
due to the very fast decarboxylation step, the reaction pro-
ceeds via a rate determining electron transfer. Working with a
substrate excess, excellent first-order kinetics were observed,
allowing us to determine rate constants (kobs) by eqn. (1).



[
Co W] = [Co W] exp(Ϫkobst)
(1)
0
The values of kobs thus obtained are displayed in Tables 1
and 2.
It was found that k is unaffected by the concentration of
obs


the oxidant (Co W) as well as by the concentration of its



reduced form (Co W). The lack of a kinetic effect by Co W
clearly indicates that if an electron transfer step is occurring it is
1
1,13
the rate determining one.
It was also observed that k increases with increasing pH,
Scheme 2
obs
Ϫ3 Ϫ1
Ϫ2 Ϫ1
going from 5.0 × 10
s
at pH = 2.15 to 8.6 × 10
s
at pH =
provided that the radical ion or radical zwitterion intermediate
is formed in the slow step.
4
.98 (Table 2), which can reasonably be explained by assuming
that the reaction rate is determined by the sum of two con-
tributions, that due to the oxidation reaction of the neutral acid
However, the observed large difference in reactivity (30 fold)
between the ionized and the neutral form of the acid, while
understandable if one considers the decarboxylation step, is
difficult to explain when, as indicated by the present kinetic
results, the rate determining step is the formation of the radical
cation. Accordingly, we cannot imagine a difference in stability
(
(
ν1) and that due to the reaction of the carboxylate anion
ν2) (eqns. (2) and (3), respectively, where the factor 2 takes
into account the fact that two moles of oxidant are consumed
for each mole of substrate. k and k are the rate constants
for electron transfer from AnCH CO H and AnCH CO ,
1
2
Ϫ
ؒ
ϩ
Ϫ
ؒ
ϩ
2
2
2
2
between An CH CO and An CH CO H (the difference
2 2 2 2
Ϫ


respectively, to Co W).
in electronic effect between –CH CO and –CH CO H is only
2
2
2
2
1
6
0
.1 σ units) so significant as to justify the observed difference

Ϫ
ν = 2k [AnCH CO H][Co W]
(2)
in oxidation rate between AnCH CO2 and AnCH CO H. It
1
1
2
2
2 2 2
would require an unreasonably large (ca. Ϫ 15) ρ value for the
oxidation reaction.
Ϫ
2

ν = 2k [AnCH CO ][Co W]
(3)
2
2
2
The possibility of a change in the site of oxidation from the
aromatic ring in AnCH CO H to the carboxylate in
It is thus possible to write for kobs
:
2
2
Ϫ
AnCH CO2 is also highly unlikely, as clearly shown by Gilbert
2
Ϫ
2
ؒ
Ϫ 17
kobs = 2(k [AnCH CO H] ϩ k [AnCH CO ])
(4)
in the oxidation of phenylalkanoic acids with SO4
.
1
2
2
2
2
J. Chem. Soc., Perkin Trans. 2, 2002, 720–722
721

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

Thus, in consideration also of the fact that no direct evidence
for the formation of a radical cation in the oxidative decarb-
Co W to reaction conditions was checked for every reaction
mixture. A cuvette containing 1 ml of a 4-methoxyphenylacetic
acid (0.020 M) solution in the pertinent buffer was placed in a
thermostated compartment of a UV–vis spectrophotometer.
After thermal equilibration at T = 20 ЊC, the reaction was
7,8
oxylation of arylacetic acids has been so far provided, the
only reasonable explanation which can be presently put forward
to explain the above results is that no radical cation inter-
mediate is actually formed, electron removal from the aromatic
ring being concerted with the intramolecular side-chain to
nucleus electron transfer, so directly leading to the carboxyl
radical which then undergoes fast decarboxylation to give the


started by rapid addition of the Co W solution (0.021 M in the


pertinent buffer: final Co W concentration in the cuvette
20
between 0.0003 and 0.0015 M). The rate of disappearance


of Co W was followed spectrophotometrically by measuring


4
-methoxybenzyl radical (Scheme 3).
the absorbance of Co W at 390 nm. The absorbance A was
recorded up to when a constant value was reached (A ; conver-
∞


sion Co W > 99%), and was related to the extent of reaction as
Co W]/[Co W] = (A Ϫ A )/(A Ϫ A ). Excellent first-order



[
0 t ∞ 0 ∞
kinetics have been observed and the observed rates (kobs) have
been derived applying eqn. (1) to the experimental data. Each
value is the average of 3–5 experiments: error ≤ 5%.
Acknowledgements
Scheme 3
Thanks are due to the Ministero dell’Istruzione dell’Università
e della Ricerca (MIUR) and to the Università “La Sapienza”
In other words, the rate determining electron transfer occurs
Ϫ
from the CO2 or CO H group, but it requires the mediation of
2
(
E. B.) for financial support.
the aromatic ring which acts as a redox relay. Thus, the ener-
getics of the oxidation is determined by both the ease of electron
abstraction from the aromatic ring and the height of the kin-
etic barrier for the intramolecular electron transfer. The latter
References
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W. W. Cleland, Acc. Chem. Res., 1999, 32, 862.
2 D. Budac and P. Wan, J. Photochem. Photobiol. A: Chem., 1992, 67,
35.
should certainly be higher for the CO H group as compared to
2
Ϫ
2
CO , since an additional proton transfer to the medium is
1
required, thus accounting for the significantly slower decarb-
3
M. Komuro, Y. Nagatsu, T. Higuchi and M. Hirobe, Tetrahedron
Lett., 1992, 33, 4949.
oxylation rate measured for AnCH CO H as compared to
2
2
Ϫ
2
AnCH CO . Of course, it is possible that with arylacetic acids
4 R. M. Dessau and E. I. Heiba, J. Org. Chem., 1975, 40, 3647.
5 W. S. Trahanovsky, J. Cramer and D. W. Brixius, J. Am. Chem. Soc.,
2
more electron rich than those hitherto studied, a mechanistic
changeover may occur with formation of an intermediate
1
974, 96, 1077.
18
6 L. Jönsson, Acta Chem. Scand., Ser. B, 1983, 37, 761.
radical cation. Work is in progress to look for this possibility.
7
8
9
S. Steenken, C. J. Warren and B. C. Gilbert, J. Chem. Soc., Perkin
Trans. 2, 1990, 335.
T. M. Bockman, S. M. Hubig and J. K. Kochi, J. Org. Chem., 1997,
Experimental
6
2, 2210.
B. Ashworth, B. C. Gilbert, R. G. G. Holmes and R. O. C. Norman,
J. Chem. Soc., Perkin Trans. 2, 1978, 951; S. Steenken, P. O’Neill and
D. Schulte-Frohlinde, J. Phys. Chem., 1977, 81, 26.
Materials
Citric acid, sodium hydroxide, sodium perchlorate and 4-meth-
oxybenzyl alcohol were of the highest commercial quality
available. HPLC grade water was used for all solutions. 4-
Methoxyphenylacetic acid (Fluka) was recrystallized twice
1
1
1
0 I. A. Weinstock, Chem. Rev., 1998, 98, 113.
1 L. Eberson, J. Am. Chem. Soc., 1983, 105, 3192.
2 M. Bietti, E. Baciocchi and J. B. F. N. Engberts, Chem. Commun.,
1
996, 1307.


from water. Co W was prepared according to a previously
1
3 The electron transfer mechanism is also confirmed by the high
sensitivity of the reaction to the electronic effects of substituents.
Accordingly, no extension of this study to arylacetic acids
substituted by less electron donating substituents than MeO (e.g.,
19
described procedure.
Product analysis

CH ) was possible, due to the too low rate of oxidation by Co W of
3
The oxidations of 4-methoxyphenylacetic acid induced by
Co W were performed in aqueous solution (pH = 3 or 5) at T =
these substrates.


1
4 G. Kortüm, W. Vogel and K. Andrussow, Dissociation Constants of
Organic Acids in Aqueous Solution, Butterworths, London, 1961.
2
5 ЊC. In a typical experiment, 5 mL of an argon saturated

15 Measured at T = 25 ЊC. The same value can be reasonably assumed
solution containing the substrate (0.02 M) and Co W (0.02 M)
were stirred until complete conversion of the oxidant. Workup
was performed as described previously. 4-Methoxybenzyl
alcohol (identified by comparison with an authentic sample)
was the exclusive reaction product.
at T = 20 ЊC, based on the observation of a 1.6% difference in the
14
value of K between 18 and 25 ЊC for phenylacetic acid
.
a
19
16 Correlation Analysis in Chemistry, eds. N. B. Chapman and
J. Shorter, Plenum Press, New York, 1978.
7 B. C. Gilbert, C. J. Scarratt, C. B. Thomas and J. Young, J. Chem.
Soc., Perkin Trans. 2, 1987, 371.
1
1
8 Of course, this work requires the application of more complex
techniques (e.g., laser flash photolysis) to detect the possible
involvement of a radical cation.
Kinetic studies
All the kinetics studied were carried out in a 1 cm quartz
cuvette previously flushed with argon. The solvent mixtures
1
2
9 E. Baciocchi, M. Bietti and M. Mattioli, J. Org. Chem., 1993, 58,
7
106.
(
citric acid–NaOH buffer solutions, pH 2.15–4.98) were

0 The concentration of Co W was at least 13 times smaller than that
thoroughly purged with argon and the ionic strength of the
solutions was buffered with 0.1 M NaClO . The stability of

of AnCH CO H (0.020 M); since two moles of Co W are needed to
2
2
1
1,12
4
oxidize one mole of substrate
it is in fact a 26-fold excess.
7
22
J. Chem. Soc., Perkin Trans. 2, 2002, 720–722