Oxidation of isoeugenol to vanillin by the "h2O 2-vanadate-pyrazine-2-carboxylic acid" reagent

Article abstract of DOI:10.1016/j.molcata.2012.06.001

Isoeugenol [2-methoxy-4-(prop-1-en-1-yl)phenol; compound 1] can be oxidized to vanillin (4-hydroxy-3-methoxybenzaldehyde, compound 2) by H ₂O₂ in the presence of the n-Bu₄NVO ₃/pyrazine-2-carboxylic acid catalyt

Full text of DOI:10.1016/j.molcata.2012.06.001

Journal of Molecular Catalysis A: Chemical 363–364 (2012) 140–147
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Oxidation of isoeugenol to vanillin by the
“H2O2–vanadate–pyrazine-2-carboxylic acid” reagentଝ
Elena V. Gusevskayaa, Luciano Meninia,1, Luciana A. Parreiraa, Rafaela A. Mesquitaa,
Yuriy N. Kozlovb, Georgiy B. Shul’pinb,∗
a Departamento de Química, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil
b Semenov Institute of Chemical Physics, Russian Academy of Sciences, ulitsa Kosygina, dom 4, Moscow 119991, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Isoeugenol [2-methoxy-4-(prop-1-en-1-yl)phenol; compound 1] can be oxidized to vanillin (4-hydroxy-
3-methoxybenzaldehyde, compound 2) by H2O2 in the presence of the n-Bu4NVO3/pyrazine-2-carboxylic
acid catalytic combination. A 50% yield of 2 was attained in a 2-h reaction at 80 ◦C, with a turnover num-
ber being higher than 1200. Kinetics of the transformation of 1 into 2 have been studied. The results
obtained indicate that the first step of the 1 activation is its interaction with a hydroxyl radical. Fur-
ther transformations of the primary product formed in this step proceed via several routes, one of
which leads to the formation of 2. It has been proposed that the interaction of vanadate with the first
molecule of H2O2 gives a V(IV)-containing species and hydroperoxyl radical: “VV–OOH” → “VIV” + HOO•.
In the next step, the V(IV) complex reacts with the second molecule of H2O2 affording a hydroxyl
radical and recovering a starting V(V)-containing species: “VIV” + H2O2 → “VV” + HO− + HO•. Then, the
hydroxyl radical attacks a double bond in the substrate: HO• + CHRꢀ CHRꢀꢀ → C•HRꢀ–CH(OH)Rꢀꢀ. The
carbon-centered radical formed in the latter step can rapidly capture a molecule of O2 from the atmo-
sphere: C•HRꢀ–CH(OH)Rꢀꢀ + O2 → C(OO•)HRꢀ–CH(OH)Rꢀꢀ. Finally, a rupture of the C C bond gives rise to
the formation of aldehyde 2.
Received 19 March 2012
Received in revised form 30 May 2012
Accepted 2 June 2012
Available online 9 June 2012
Keywords:
Hydrogen peroxide
Oxidation
Pyrazine-2-carboxylic acid
Vanadium complexes
Vanillin
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
particular, a method for the catalytic oxidation of isoeugenol to
vanillin by hydrogen peroxide has been described [6]. However,
Vanillin (4-hydroxy-3-methoxybenzaldehyde, compound
2
the reaction demands the use of the very expensive methyltriox-
orhenium as the catalyst and dangerous anhydrous H2O2.
shown in Scheme 1) is found in nature in the extract of the
vanilla beans as well as in roasted coffee and the Chinese red
pine Pinus tabuliformis. This compound is widely used as a
flavoring agent in medicine (in the production of pharmaceuti-
cals and to mask unpleasant odors or tastes of drugs) and in
food, beverage and perfume industries (e.g., in the production of
ice creams, sweets and chocolates). The world annual demand
for vanillin is 12,000 tons; however, only 1800 tons are pro-
duced from natural sources [2]. Vanillin can be prepared from
eugenol (4-allyl-2-methoxyphenol) or isoeugenol [2-methoxy-4-
(prop-1-en-1-yl)phenol; its trans-isomer is shown as compound
1 in Scheme 1] biotechnologically [3] or synthetically [4,5]. In
Vanadium complexes are known as efficient catalysts for var-
ious mild oxidations of organic compounds [7–14], particularly,
saturated [15–19], aromatic [20–23] and olefinic [24–27] hydrocar-
bons as well as natural products [28–30]. In most of these processes,
hydrogen peroxide was used as the oxidizing reagent (usually in an
air atmosphere); however, the applications of other peroxides, such
as tert-butyl hydroperoxide [31,32] and peroxyacetic acid [33], in
these oxidations were also described. Vanadium compounds are
also good catalysts in the Sen–Fujiwara–Pombeiro reaction (i.e.
the metal-catalyzed and non-catalyzed carboxylation of hydrocar-
2−
bons to carboxylic acids with CO under the action of the S2O8
anion; see reviews [12,19,34,35] and selected original publications
[36,37]). Earlier one of us has discovered that the vanadate anion
(as well as other soluble vanadium-containing compounds) effi-
ciently catalyzes the oxidation of organic compounds by H2O2 in
acetonitrile solutions in the presence of small amounts of pyrazine-
2-carboxylic acid (PCA pcaH) as the co-catalyst [1,38–44]. Alkanes
[1,38,39], olefins [38,40,41], aromatic hydrocarbons [38] and alco-
hols [1,38] can be successfully oxidized by this reagent. Based on a
ଝ
Part 17 of the series “Oxidations by the reagent ‘H2O2–vanadium
derivative–pyrazine-2-carboxylic acid”’. For Part 16, see ref. [1].
∗
Corresponding author.
E-mail address: shulpin@chph.ras.ru (G.B. Shul’pin).
Present address: Campus de Alegre, Instituto Federal de Educac¸ ão, Ciência e
1
Tecnologia do Espírito Santo, 29500-000, Caixa Postal 47, Alegre, ES, Brazil.
1381-1169/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2012.06.001

E.V. Gusevskaya et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 140–147
141
H
H
CH2
CH3
H2O2, n-Bu4NVO3, air, in MeCN
CH3
O
+
O
H
N
COOH
HO
HO
HO
OCH3
Ketone (3)
OCH3
OCH3
Isoeugenol (1)
N
Vanillin (2)
Pyrazine-2-carboxylic acid
(PCA)
Scheme 1.
kinetic study of the alkane oxidation, we have proposed [1,42–44]
the mechanism involving the V(V)–V(IV) manifold in two crucial
steps: the decomposition of a transient peroxovanadium(V) com-
plex to produce a peroxyl radical and a V(IV) species (Eq. (A)) and
further interaction of this V(IV) complex with the second hydrogen
peroxide molecule to afford a hydroxyl radical (Eq. (B)) which then
attacks the hydrocarbon substrate.
In a further study, the initial concentrations of PCA were varied
(Fig. 6). Based on results obtained in these experiments and consid-
ering the data presented in Figs. 2 and 3, we found the dependences
of the initial rates of the isoeugenol consumption, W01, and vanillin
accumulation, W02, on the PCA concentration (Fig. 7).
Finally, the oxidation of isoeugenol at different initial concentra-
tions of H2O2 was studied (Fig. 8) to evaluate the effects of [H2O2]0
on W01 and W02 (Fig. 9).
“VV–OOHꢀꢀ → “VIVꢀꢀ + HOO•
(A)
(B)
The experimental material presented above indicates that (i)
as noted previously, the concentration of vanillin formed in the
reaction solutions in all runs is considerably higher than that of
ketone 3, so that we really can neglect product 3 in kinetic consid-
“VIVꢀꢀ + H2O2 → “VVꢀꢀ + HO− + HO•
The presence of PCA dramatically accelerates the reaction of the
H2O2 decomposition as confirmed by DFT calculations [44,45]: the
activation barrier of the HO• formation in the presence of PCA is
by 9.6 kcal/mol lower than that in the absence of PCA [44,46]. In
this work, we have applied the H2O2–vanadate–PCA reagent to the
practically very important oxidation of isoeugenol into vanillin (see
Scheme 1). The mechanism of this oxidation has been also studied.
erations; (ii) the initial rate of the isoeugenol consumption, W01
−d[1]/dt, is higher than the initial rate of the vanillin accumulation,
=
0.20
0.16
A
80
60
2. Results and discussion
1
0.12
0.08
0.04
0
We have found that vanadate anion in the form of the salt
n-Bu4NVO3 effectively catalyzes the oxidation of isoeugenol (com-
pound 1) with H2O2 in the presence of pyrazine-2-carboxylic acid
(PCA). The main product of the reaction is vanillin (compound 2)
along with ketone 3 formed in much lower amounts. Examples of
the kinetic curves of the isoeugenol consumption and product accu-
mulation under various conditions are presented in Figs. 1 and 2.
It can be seen that at 80 ◦C the reaction gave vanillin in 50% yield
after 2 h, with a total turnover number (TON) for products 2 and 3
based on vanadium being 1200 (Fig. 1B).
2
40
20
3
0
At 40 ◦C, the oxidation proceeds slower. However, it was more
convenient to perform the kinetic study for the transformations
at 40 ◦C. Under these conditions, we obtained kinetic curves for
the reaction varying initial concentrations of each reactant at con-
stant initial concentrations of all other components. In the first
series of our experiments, the effect of the initial concentration
of n-Bu4NVO3 on the initial rates of the 1 consumption and the
accumulation of products 2 and 3 was investigated. The kinetic
curves obtained in these experiments are demonstrated in Fig. 2. As
the concentration of ketone 3 in the reaction solutions was low in
all runs, this product was neglected in our kinetic considerations.
The dependences of the initial rates of the isoeugenol consump-
tion, W01 = −d[1]/dt, and vanillin accumulation, W02 = d[2]/dt, on
[Bu4NVO3]0 are presented in Fig. 3. These data are based on the
results shown in Fig. 2.
The kinetic curves of the isoeugenol consumption as well as the
accumulation of vanillin and the ketone at different initial concen-
trations of isoeugenol are presented in Fig. 4. Based on these data
as well as the data presented in Figs. 2 and 3, the dependences of
the initial rates of the isoeugenol consumption, W01, and vanillin
accumulation, W02, on the initial concentration of isoeugenol were
evaluated (Fig. 5).
0.20
0.16
0.12
B
80
60
1
2
40
0.08
0.04
20
0
3
0
0
1.0
1.5
2.0
0.5
Time, h
Fig. 1. Consumption of isoeugenol (1, initial concentration 0.2 M) and accumulation
of vanillin (2) and ketone (3) in the oxidation of isoeugenol with H2O2 (initial con-
centration 0.4 M) catalyzed by n-Bu4NVO3 (1 × 10−4 M) at different concentrations
of the co-catalyst (PCA): 2 × 10−4 M (graph A) and 4 × 10−4 M (graph B). Solvent was
MeCN, temperature 80 ◦C.

142
E.V. Gusevskaya et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 140–147
0.20
0.16
12
[vanadate]0 = 0.5 ×10−4 M
80
60
40
20
0
10
W01 = −d[1]/dt
0.12
0.08
1
8
6
2
3
0.04
0
W02 = d[2]/dt
4
2
0
0.20
[vanadate]0 = 1.0 ×10−4 M
80
60
40
20
0
0.16
0.12
0.08
0
2.0
104 × [vanadate]0, M
3.0
1.0
1
Fig. 3. Dependences of the initial rates of the isoeugenol consumption, W01, and
vanillin accumulation, W02, on the initial vanadate concentration, which were cal-
culated from the kinetic curves shown in Fig. 2.
2
0.04
0
3
W02 = d[2]/dt. To clarify the reason for the latter observation, we
have studied the oxidation of both isoeugenol and vanillin under
the same conditions in separate experiments. The data obtained
(shown in Fig. 10) testify that the difference between W01 and W02
cannot be explained by the efficient concomitant over-oxidation
of vanillin. Although vanillin really undergoes a further oxidation
in our process, the initial rate of its oxidation is much lower than
that of the oxidation of isoeugenol under the same conditions (at
the initial concentration 0.1 M; see Fig. 10). It should be also con-
sidered that the concentration of vanillin in the beginning of the
reaction is low, so that the vanillin over-oxidation could not be
responsible alone for the difference between W01 and W02. Hence,
we have to assume that W01 is higher than W02 because the trans-
formation of isoeugenol under the reaction conditions gives, along
with the identified products 2 and 3, considerable amounts of the
product(s) which is (are) not determinable by gas chromatography
(GC). In other words, isoeugenol is transformed via several parallel
routes, with one of these pathways leading to vanillin. Furthermore,
as vanillin is oxidized under the reaction conditions (though less
efficiently than 1, see Fig. 10), its maximum yields obtained in the
course of the reactions were lower than the values which could be
expected based on the initial rates of the isoeugenol consumption
and vanillin accumulation.
0.20
[vanadate]0 = 2.0 ×10−4 M
80
60
40
20
0
0.16
0.12
1
0.08
0.04
0
2
3
0.20
[vanadate]0 = 3.0 ×10−4 M
80
60
40
20
0
0.16
0.12
The dependences of the initial reaction rates on the initial con-
centrations of n-Bu4NVO3 (Fig. 3), isoeugenol (Fig. 5) and PCA
(Fig. 7) indicate that the rates of the isoeugenol consumption and
the vanillin accumulation are completely congruous: both rates are
proportional to [n-Bu4NVO3]0 and the modes of their dependences
on [isoeugenol]0 and [PCA]0 are identical. This fact testifies that the
rate-limiting steps in the processes of the isoeugenol oxidation and
the vanillin formation are the same.
1
2
0.08
0.04
0
3
In previous studies on the alkane oxidations in similar sys-
tems [1,9,10,42,44], based on the DFT calculations and analysis
of the reaction selectivities and kinetic features some of us have
concluded that active species which induce transformations of
alkane in the “H2O2–vanadate–PCA” oxidation system are hydroxyl
radicals. It is reasonable to propose that the isoeugenol oxygena-
tion into vanillin by the same system also proceeds with the
0
1.0
Time, h
1.5
2.0
0.5
Fig. 2. Consumption of isoeugenol (initial concentration 0.2 M, compound 1) and
accumulation of vanillin (2) and ketone (3) in the oxidation of isoeugenol with
H2O2 (initial concentration 0.4 M) catalyzed by n-Bu4NVO3 at its different initial
concentrations (written in the graphs) and PCA (4 × 10−4 M). Solvent was MeCN,
temperature 40 ◦C.

E.V. Gusevskaya et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 140–147
143
A
0.10
0.08
0.06
6
[1]0 = 0.1 M
5
80
60
40
20
W01 = −d[1]/dt
4
3
1
2
0.04
0.02
0
2
1
0
W02 = d[2]/dt
3
0
0.5
0.05
[1]0 = 0.3 M
0.2
[1]0, M
0
0.3
0.4
0.1
0.4
0.3
0.04
0.03
0.02
0.01
2
10−4
10−4
B
, M−1 s
, M−1 s
3
1
2
W0
W0
6
4
2
0
1
0.2
2
1
0
0.1
0
3
0
0
4
6
10
2
8
0.5
0.05
[1]0 = 0.4 M
1/[1]0, M−1
2
0.4
0.3
0.04
0.03
0.02
0.01
0
Fig. 5. Graph A: dependences of the initial rates of the isoeugenol consumption,
W01, and vanillin accumulation, W02, on the initial isoeugenol concentration which
were calculated from the data shown in Fig. 4. Graph B: the linearization of the
dependences presented in graph A in coordinates (1/W0)–(1/[1]0).
1
0.2
0.1
0
the reaction solution [42]. If we assume that the oxidizing species is
hydroxyl radical, we can suggest that the most probable other com-
ponent which interacts with HO• is acetonitrile [1,42]. The rates of
the interaction of HO• with PCA or H2O2 are much lower than with
MeCN. Taking into account that the yield of vanillin corresponds to
only a portion of the isoeugenol reacted we can propose the fol-
lowing kinetic scheme for the competitive oxidation of isoeugenol
and formation of vanillin:
3
0
1.0
Time, h
1.5
2.0
0.5
Fig. 4. Consumption of isoeugenol (1) at its different initial concentrations (writ-
ten in the graphs) and accumulation of vanillin (2) and ketone (3) with time in
the oxidation of isoeugenol with H2O2 (initial concentration 0.4 M) catalyzed by n-
Bu4NVO3 (1 × 10−4 M) and PCA (4 × 10−4 M). Solvent was MeCN, temperature 40 ◦C.
The kinetic curves at [1]0 = 0.2 M are given in Fig. 2 ([vanadate]0 = 1 × 10−4 M).
“H2O2–vanadate–PCAꢀꢀ → HO•,
HO• + MeCN → products
initiation rate Wi
(1)
(2)
(3)
HO• + isoeugenol (1) → vanillin (2)
participation of hydroxyl radicals. The existence of different routes
of the isoeugenol transformation which occur at comparable rates
reflects the fact that the reactivities of different fragments of the 1
molecule towards the oxidizing species are similar. The relatively
low selectivity of the oxidation of isoeugenol (in other words, the
involvement of various fragments of the molecule in the reaction)
is in an agreement with our assumption that the reactive species
are hydroxyl radicals.
The results of the kinetic experiments presented in Fig. 5 also
support the proposal about the hydroxyl radical participation. The
dependences of W01 and W02 on the isoeugenol concentration (Fig. 5)
are typical for the case of a competitive interaction of the oxidizing
species with the substrate (isoeugenol) and another component of
HO• + isoeugenol (1) → ketone (3) and unidentified products (3ꢀ)
Here stage (1) is the efficient reaction of the catalytic generation
of hydroxyl radicals when H2O2 is decomposed under the action
of vanadate and PCA (the rate-limiting step); (2) is the stage of the
disappearance of hydroxyl radicals in the course of their interac-
tion with MeCN; (3) is the stage of the interaction between hydroxyl
radicals and isoeugenol limiting the formation of vanillin; (3ꢀ) is the
stage of the interaction between hydroxyl radicals and isoeugenol
limiting the formation of ketone 3 and all unidentified products.
The analysis of this kinetic scheme assuming that the concentra-
tion of hydroxyl radicals is quasi-stationary led to the following

144
E.V. Gusevskaya et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 140–147
A
12
0.20
0.16
0.12
[PCA]0 = 2.0 ×10−4 M
10
80
60
40
20
0
W01 = −d[1]/dt
8
6
4
1
2
0.08
0.04
W02 = d[2]/dt
3
2
0
0
0.20
[PCA]0 = 8.0 ×10−4 M
0
8
12
4
104 × [PCA]0, M
80
60
40
20
0
0.16
0.12
1
10−4
10−4
W0
B
, M−1 s
, M−1 s
3
2
1
W0
12
2
0.08
0.04
0
8
2
1
0
4
3
0
0
2
3
1
4
5
0.20
10−3/[PCA]0, M−1
[PCA]0 = 12.0 ×10−4 M
Fig. 7. Graph A: dependences of the initial rates of the isoeugenol consumption,
W01, and vanillin accumulation, W02, on the PCA concentration. The data presented
in Figs. 2, 3 and 6 were used. Graph B: the linearization of the dependences presented
in graph A in coordinates (1/W0)–(1/[PCA]0).
80
60
40
20
0
0.16
0.12
1
ꢀ
in Fig. 5B that the values k2[MeCN]/(k3 + k3 ) measured based on the
0.08
0.04
0
data for the isoeugenol consumption (0.05) and the vanillin forma-
tion (0.07) are very close. This result is in accord with the proposal
for the reaction mechanism. On the other hand, the absolute value
2
ꢀ
k2[MeCN]/(k3 + k3 ) is typical for the reactions of hydroxyl radicals
3
with hydrocarbons in acetonitrile solutions [42].
The dependence presented in Fig. 7A can be associated with the
formation of the vanadate/PCA adduct (adduct). This adduct, unlike
starting vanadate ions, exhibits a catalytic activity in the generation
of hydroxyl radicals from hydrogen peroxide. Taking into account
the equilibrium
0
1.0
Time, h
1.5
2.0
0.5
Fig. 6. Consumption of isoeugenol (1, initial concentration 0.2 M) and accumula-
tion of vanillin (2) and ketone (3) in the oxidation of isoeugenol with H2O2 (initial
concentration 0.4 M) catalyzed by n-Bu4NVO3 (1 × 10−4 M) and PCA at its different
concentrations (written in the graphs). Solvent was MeCN, temperature 40 ◦C. The
kinetic curves at [PCA]0 = 4 × 10−4 M are given in Fig. 2 ([vanadate]0 = 1 × 10−4 M).
vanadate + PCA ꢀ adduct, constant K6
(6)
which exists under the experimental conditions shown in Fig. 7A
and also the condition [vanadate]0 < [PCA]0, we have obtained the
expression for the equilibrium concentration of the adduct:
expressions for the rate of the vanillin formation and the total rate
of the isoeugenol transformation:
K6[vanadate]0[PCA]0
[adduct] =
(7)
1 + K6[PCA]0
d[2]
dt
k3
Wi
W02
=
=
×
(4)
ꢀ
ꢀ
k3 + k3
1 + (k2[MeCN]/(k3 + k3 )[1])
where K6 is the equilibrium constant of process (6). Obtaining
expression (7) we have also assumed that a portion of PCA bound
to the vanadium is not large, that is [adduct]/[PCA]0 is noticeably
less than unity. Let us assume further that the initial reaction rate
is proportional to the concentration of adduct, that is
d[1]
dt
Wi
W01 = −
= (k3 + k3 )[HO ][1] =
•
ꢀ
1 + (k2[MeCN]/(k3 + k3ꢀ )[1])
(5)
W0j = ꢀj[adduct]
(8)
The experimental data presented in Fig. 5B are in agreement with
Eqs. (4) and (5) because in both cases the dependences of recipro-
cals of the reaction rates on the reciprocal isoeugenol concentration
are satisfactorily linear. It follows from the dependences presented
where W0j is either the isoeugenol consumption rate (j = 1) or
the vanillin formation rate (j = 2) with the corresponding effective

E.V. Gusevskaya et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 140–147
145
0.20
0.16
0.12
12
[H2O2]0 = 0.2 M
80
60
40
20
0
W01 = −d[1]/dt
10
1
4
8
6
0.08
0.04
0
3
2
2
4
2
0
3
W02 = d[2]/dt
1
0
0.20
[H2O2]0 = 0.6 M
80
60
40
20
0
0.16
0.12
0
0.6
[H2O2]0, M
0.8
0.4
0.2
Fig. 9. Dependences of the isoeugenol consumption initial rates, W01, and vanillin
accumulation initial rates, W02, on the H2O2 concentration. The data presented in
Figs. 2, 3 and 8 were used.
1
0.08
0.04
0
linear dependences for both the transformation of isoeugenol and
the formation of vanillin can be seen in Fig. 5B. The analysis of these
dependences led to the values K6 = 0.8 × 103 M−1 for isoeugenol
and K6 = 1.0 × 103 M−1 for vanillin which are really the same value.
Taking K6 = 103 M−1 we can estimate that under our experimen-
tal conditions [adduct]/[PCA]0 = K6[vanadate]0/(1 + K6[PCA]0) is less
than 0.1. It means that previously assumed condition of the low
degree of PCA bounding by vanadium ions is obeyed.
2
3
0.20
[H2O2]0 = 0.8 M
1
0.04
0.03
0.02
0.01
0
0.16
0.12
The linear dependence of the rates W01 and W02 on the ini-
tial concentration of vanadate (Fig. 3; see Eqs. (8) and (7)) is in
agreement with the assumption about the catalytic activity of the
vanadate/PCA adduct. The rate of the isoeugenol transformation is
proportional to the concentration of H2O2, whereas for the rate
of the vanillin accumulation some deviation from linearity can
be noticed (Fig. 9). This phenomenon is different from the situa-
tion with three other kinetic dependences where the rate of the
2
0.08
0.04
0
3
0.10
+
0
1.0
Time, h
1.5
2.0
0.5
+
0.08
+
Fig. 8. Consumption of isoeugenol (1, initial concentration 0.2 M) and accumulation
of vanillin (2) and ketone (3) in the oxidation of isoeugenol with H2O2 at its differ-
ent concentrations (written on the graphs) catalyzed by n-Bu4NVO3 (1 × 10−4 M)
and PCA (4 × 10−4 M). Solvent was MeCN, temperature 40 ◦C. The kinetic curves at
[H2O2]0 = 0.4 M are given in Fig. 2 ([vanadate]0 = 1 × 10−4 M).
+
+++
2
+
+
+
0.06
constants ꢀj (j = 1 for isoeugenol and j = 2 for vanillin). We will come
to the following common equation for the initial reaction rates:
0.04
K6[vanadate]0[PCA]0
1
W0j = ꢀj
(9)
0.02
1 + K6[PCA]0
Let us now transform Eq. (9) into the following expression:
0
1
1
1
1
=
+
×
(10)
0
1.0
1.5
2.0
0.5
W0j
ꢀj[vanadate]0
ꢀj[vanadate]0K6
[PCA]0
Time, h
If our explanation of the dependence of the initial reaction rate
on the concentration of PCA is correct we should find, in accord
with Eq. (10), the linear dependence of the reciprocal of the reac-
tion rate on the reciprocal of the PCA concentration. Indeed, these
Fig. 10. Consumption of vanillin (2, initial concentration 0.1 M) and isoeugenol (1,
initial concentration 0.1 M) in their separate oxidations with H2O2 (initial concen-
tration 0.4 M) catalyzed by n-Bu4NVO3 (1 × 10−4 M) and PCA (4 × 10−4 M). Solvent
was MeCN, temperature 40 ◦C.

146
E.V. Gusevskaya et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 140–147
isoeugenol consumption and the vanillin accumulation are com-
pletely congruous. However, it should be taken into account that
in first three cases (effects of the vanadate, PCA, and isoeugenol
concentrations), we have varied only the concentration of one com-
ponent in each kinetic experiment. On the other hand, during the
study of the H2O2 effect the concentration of water in the reaction
solutions was varied together with the concentration of H2O2 as the
latter reagent was used as an aqueous solution. Previously we have
demonstrated that at relatively high concentrations of added water
the rate of the hydroxyl radical generation drops [1,42]. It is reason-
able to suggest that rate dependences on the water concentration
for the isoeugenol transformation and the vanillin over-oxidation
are different. A more pronounced effect of added water on the
oxidation of vanillin is expected because this compound is more
hydrophilic so that the addition of water could facilitate its oxida-
tion with hydroxyl radicals.
Initially, a portion of H2O2 (a 29% aqueous solution from Synth) was
added to the solution of the catalyst, co-catalyst and substrate. After
certain time intervals samples (about 0.2 mL) were taken. The sam-
ples of reaction solutions were analyzed by GC using a Shimadzu
17A instrument fitted with a Carbowax 20M capillary column and a
flame ionization detector. The details of the experiments are given
in the captions for figures. The structures of the products were
confirmed by GC/MS (Shimadzu QP2010-PLUS instrument, 70 eV).
There was no difference in the chromatograms obtained before
and after treatment of the samples with PPh3 (for this method
developed earlier by one of us, which allows us to estimate real
concentrations of alkyl hydroperoxide, ketone and alcohol formed
in alkane oxidations, see Refs. [9,10,51–55]). This indicates that the
oxidation of isoeugenol does not take place in the chromatograph
but only in the reaction vessel.
We found the support for this proposal in specially performed
additional experiments. It was found that the addition of water
(2.2 M) to the reaction solution under our standard conditions led
to the decrease of the isoeugenol consumption rate only by a factor
of 2, whereas the rate of the vanillin formation dropped more than
10 times. This experiment explains why at high concentrations of
H2O2 and, consequently, H2O the yield of vanillin decreases (Fig. 8).
Hydroxyl radicals can attack the double bond of isoeugenol to
produce carbon-centered radicals which rapidly capture molecules
of O2 from the atmosphere. Further splitting the C C bond leads to
the formation of the aldehyde group of vanillin. It should be noted
that only a small portion of hydroxyl radicals (less than 10%) is con-
sumed in their reaction with solvent acetonitrile (see Fig. 5). Thus,
the main portion of H2O2 is used for the isoeugenol oxidation. How-
ever, unfortunately all other common solvents which have been
studied by us previously are much more reactive in comparison
with acetonitrile and they cannot be employed in our reaction.
It is necessary to emphasize that both the substrate (isoeugenol)
and the product (vanillin) are very reactive compounds. In the case
of acetonitrile, the non-quantitative yield of vanillin was due to
the over-oxidation of vanillin and not to the competitive oxida-
tion of isoeugenol and acetonitrile. As Fig. 10 demonstrates, vanillin
is oxidized further more slowly (2–3 times) than isoeugenol. This
is the reason why we can attain the substantially high yield of
vanillin. An analysis of the consecutive transformation of a sub-
strate (isoeugenol) into the product (vanillin) when both these
compounds are of comparable reactivity is given in Appendix to
this paper.
Acknowledgments
The authors thank CNPq, CAPES, FAPEMIG, INCT-Catálise (Brazil)
and the Russian Foundation for Basic Research (grant 12-03-00084-
a) for the financial support. The authors are also grateful to André
C. Ferreira for the experimental assistance.
Appendix. Formal kinetic calculations of a maximum
possible yield
It is important to estimate from formal kinetic calculations a
maximum possible yield of the product of the reaction in which
both a substrate (in our case isoeugenol) and the product (vanillin)
are of comparable reactivities in the interaction with oxidizing
species X (in our case: hydroxyl radicals). We restrict our calcula-
tions only by the formation and decomposition of the first primary
product (vanillin).
Let us consider the consequence of transformations of a substrate
to the primary product and further oxidation of the primary prod-
uct to secondary products. All these transformations are induced by
oxidizing species X which are generated in our catalytic system:
+X
+X
substrate−→ primary product−→ secondary products
(A0)
Let us assume further that the rate limiting stages in these
transformations are the interactions between X and substrate and
between X and primary product. In this case we come to the simple
kinetic scheme:
An alternative mechanism can include the epoxide formation
which is further oxidized to give the aldehyde [47]. However, as it
has been recently shown by DFT calculations [48,49] our mecha-
nism which includes the consecutive formation of HOO• and HO•
radicals as well as the involvement of the V(IV)–V(V) manifold
[1,9,10,42,44,50] is more reasonable.
substrate + X → primary product, k1
(A1)
(A2)
primary product + X → secondary products, k2
where both substrate and primary product react with oxidizing
species X. Schemes (A1) and (A2) are equivalent to the sequence
of monomolecular transformations A → B → C with effective rate
first order constants relative substrate and primary product: k1[X]
and k2[X]. The analysis of this scheme for the maximum attained
yield of primary product gives the following expression:
3. Conclusions
ꢀ
ꢁ
(k /k )/(1−(k /k ))
2
1
2
1
The reagent ‘H2O2–vanadium derivative–pyrazine-2-carboxylic
acid’ very efficiently transforms isoeugenol to vanillin under mild
conditions.
[primary products]max
[substrate]0
k2
k1
=
(A3)
The values of maximum possible yield of primary product
(100 × [primary product]max/[substrate]0, %) for some k2/k1 ratios
calculated in accord with formula (A3) are given in Table A1.
It can be seen from the data of Table A1 that if reactivity of
intermediate primary product (vanillin) is only two times lower
than reactivity of starting substrate (isoeugenol) in their interac-
tion with species X the maximum yield of the intermediate vanillin
could attain 50%. If primary product is four times less reactive
in comparison with substrate the yield of 63% can be attained.
As Fig. 10 demonstrates, vanillin is oxidized further more slowly
4. Experimental
All reagents were purchased from commercial sources and used
as received. Isoeugenol (a mixture of cis and trans isomers) from
Aldrich was used as the substrate. Catalyst [42] and co-catalyst
(PCA) were used as stock solutions. The oxidations of 1 were carried
out in MeCN in air in thermostated Pyrex vessels with vigor-
ous stirring. The total volume of the reaction solution was 5 mL.

E.V. Gusevskaya et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 140–147
147
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