Oxygenation of Methylarenes to Benzaldehyde Derivatives by a Polyoxometalate Mediated Electron Transfer-Oxygen Transfer Reaction in Aqueous Sulfuric Acid

Article abstract of DOI:10.1021/jacs.5b01745

The synthesis of benzaldehyde derivatives by oxygenation of methylarenes is of significant conceptual and practical interest because these compounds are important chemical intermediates whose synthesis is still carried out by nonsustainable methods with very low atom economy and formation of copious amounts of waste. Now an oxygenation reaction with a 100% theoretical atom economy using a polyoxometalate oxygen donor has been found. The product yield is typically above 95% with no "overoxidation" to benzoic acids; H₂ is released by electrolysis, enabling additional reaction cycles. An electrocatalytic cycle is also feasible. This reaction is possible through the use of an aqueous sulfuric acid solvent, in an aqueous biphasic reaction mode that also allows simple catalyst recycling and recovery. The solvent plays a key role in the reaction mechanism by protonating the polyoxometalate thereby enabling the activation of the methylarenes by an electron transfer process. After additional proton transfer and oxygen transfer steps, benzylic alcohols are formed that further react by an electron transfer-proton transfer sequence forming benzaldehyde derivatives. (Chemical Equation Presented).

Full text of DOI:10.1021/jacs.5b01745

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Article
Oxygenation of Methylarenes to Benzaldehyde Derivatives
by a Polyoxometalate Mediated Electron Transfer-
Oxygen Transfer Reaction in Aqueous Sulfuric Acid
Bidyut Bikash Sarma, Irena Efremenko, and Ronny Neumann
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b01745 • Publication Date (Web): 22 Apr 2015
Downloaded from http://pubs.acs.org on April 29, 2015
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Oxygenation of Methylarenes to Benzaldehyde Derivatives by a Pol-
yoxometalate Mediated Electron Transfer-Oxygen Transfer Reac-
tion in Aqueous Sulfuric Acid
Bidyut Bikash Sarma, Irena Efremenko and Ronny Neumann*
Department of Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel 76100
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Supporting Information Placeholder
mation more probable. Surprisingly, despite the perꢀ
ceived easier oxygenation of alkylarenes, a selective,
high yield reaction of methylarenes, ArCH3, to benzalꢀ
dehyde derivatives, ArCHO, remains a considerable
challenge, especially in the context of green, waste free
transformations with a high atom economy, because
aerobic and peroxide oxidation strongly tends to yield
benzoic acid derivatives as the major product.5 A perusal
of the literature describing the synthesis of benzaldehyde
derivatives shows that there are five major reaction
pathways. The first pathway is formylation reactions of
arenes by various methods such as the GattermanꢀKoch
reaction,6 the Gatterman reaction,7 the VilsmeierꢀHaack
reaction,8 the ReimerꢀTiemann reaction,9 the use of diꢀ
chloromethyl methyl ether and aluminum chloride,10 or
formylfluoride/boron trifluoride.11 All these reactions
form copious amounts of waste, and often use or proꢀ
duce toxic compounds. They are not general for all subꢀ
strates and not regioselective, thus requiring product
separation. Second, use of molecular halogens X2, X =
Cl, Br, either through free radical halogenation of
methylarenes followed by hydrolysis to yield the reꢀ
quired aldehyde,12 or by halogenation of arenes to the
corresponding haloarenes followed by carbonylation
with carbon monoxide typically using palladium cataꢀ
lysts.13 Obviously these reactions produce large quantiꢀ
ties of halide waste. Methylarenes can be oxidized to the
corresponding carboxylic acids, by a large variety of
methods but also catalytically with O2 using the classic
autooxidation Co/Mn/Br catalysts.5 The carboxylic acid
can then be reduced, typically via formation of an
acylchloride followed by reduction.14 Single step highly
selective catalytic formation of ArCHO from ArCH3 in
high yields with benign oxidants has not been demonꢀ
strated, although using stoichiometric reagents such as
chromyl chloride,15 permanganate,16 manganese dioxꢀ
ide,17 hypervalent iodine compounds,18 and cerium oxiꢀ
dants19 can be effective. Recently, there have been some
reports on new catalysts for the oxidation of ArCH3
compounds such as PdꢀAu nanoparticles supported on
ABSTRACT: The synthesis of benzaldehyde derivatives
by oxygenation of methylarenes is of significant concepꢀ
tual and practical interest because these compounds are
important chemical intermediates whose synthesis is still
carried out by nonꢀsustainable methods with very low
atom economy and formation of copious amounts of
waste. Now an oxygenation reaction with a 100 % theoꢀ
retical atom economy using a polyoxometalate oxygen
donor has been found. The product yield is typically
above 95% with no “over oxidation” to benzoic acids;
H2 is released by electrolysis, enabling additional reacꢀ
tion cycles. An electrocatalytic cycle is also feasible.
This reaction is possible through the use of an aqueous
sulfuric acid solvent, in an aqueous biphasic reaction
mode that also allows to simple catalyst recycle and
recovery. The solvent plays a key role in the reaction
mechanism by protonating the polyoxometalate thereby
enabling the activation of the methylarenes by an elecꢀ
tron transfer process. After additional proton transfer and
oxygen transfer steps, benzylic alcohols are formed that
further react by an electron transferꢀproton transfer seꢀ
quence forming benzaldehyde derivatives.
Introduction
Carbonꢀhydrogen bond activation of alkanes and relatꢀ
ed oxygen insertion leading to hydroxylated products
remains a highly desirable and important chemical transꢀ
formation with broad implications in many areas ranging
from the energy sector, for example methane to methaꢀ
nol, to transformations in the fine chemical industry.
Much of the more recent research in homogeneous phase
catalytic hydroxylation has been devoted to enzymatic
reactions and the use of related biomimetic analogues as
catalysts.1,2 Iron based heme and nonꢀheme catalysts
have been the most studied compounds.3,4 An important
subꢀclass of alkane hydroxylation reactions is the oxyꢀ
genation of alkylarenes, where the weaker benzylic carꢀ
bonꢀhydrogen bond makes such a selective transforꢀ
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Page 2 of 8
carbon or TiO2,20 Cuꢀbased heterogeneous catalysts,21
mol%) of the corresponding carboxylic acid, ArCOOH.
and thermally treated melamine.22 Conversion and/or
selectivity to benzaldehyde is low.
Also, no sulfonated products were detected. For toluene
and halogen substituted derivatives as electron withꢀ
drawing moieties nearly quantitative conversions were
observed with very high selectivity to ArCHO.
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Previous research has shown that phosphovanadomoꢀ
lybdate polyoxometalates, most notably H5PV2Mo10O40
is reactive in electron transferꢀoxygen transfer (ETꢀOT)
reactions that, for example, can lead insertion of oxygen
from H5PV2Mo10O40 into a CꢀH bond.23 For example, an
alkylarene with a low oxidation potential, such as xanꢀ
thene, was shown to react in this manner to yield xanꢀ
thone as product.24ꢀ25 However, no reaction occurred
with substrates with higher oxidation potential notably
toluene and alike. Recently, we have demonstrated that
(ETꢀOT) reactions, active for cleavage of CꢀC bonds of
primary alcohols and vicinal diols,26 can transform carꢀ
bohydrates to synthesis gas.27 Important in the context
of this research, it was observed that such reactions are
considerably accelerated using mineral acids as solvents,
leading us the proposition that reactions that were not
enabled in typical organic solvents may be possible in
mineral acids. Indeed, we now demonstrate for the first
time the two stage very high yield and selective oxidaꢀ
tion of ArCH3, to ArCHO with a theoretical atom econꢀ
omy of 100%, Scheme 1. First ArCHO is formed in an
ETꢀOT oxygenation reaction and then H2 as the addiꢀ
tional product is released by electrolysis. The reaction
can also be carried out electrocatalytically. Cyclic voltꢀ
ammetry and DFT calculations coupled with mechanisꢀ
tic probe reactions shows why mineral acids may be
superior solvents for such ETꢀOT transformations.
Table 1. ET-OT oxidation of ArCH3 compounds to Ar-
CHO
R in Rꢀ
C6H4CH3
Time, Temperꢀ
Converꢀ
Selectiviꢀ
ty, mol%
9
h
5
5
5
5
5
5
ature, °C sion, mol%
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H
4ꢀMe
70
60
70
60
50
50
99
99
99
99
80
90
95
94
94
89
80
85
3ꢀMe
2ꢀMe
2,4ꢀdiMe[a]
1,3,5ꢀ
triMe
4ꢀOMe
4ꢀi-Pr
4ꢀt-Bu
4ꢀF
24
24
12
5
5ꢀ22[b]
5ꢀ22[b]
30
85
60
93
99
99
98
97
98
98
90
45
75
30[c]
89[d]
98
70
4ꢀCl
7
80
97
4ꢀBr
10
10
8
80
96
4ꢀI
80
96
3ꢀCl
80
93
3ꢀBr
7
80
94
CHO
H2SO4
2,4,ꢀdiCl
12
24
90
96
+
+ H2O + 2
2
[e]
R
R
4ꢀNO2
90
98
Oxidized
H5PV2Mo10O40
Reduced
H7PV2Mo10O40
electrolysis
Reaction conditions: 0.461 mmol ArCH3, 0.922 mmol
H5PV2Mo10O40•32H2O, 8 mL 50% H2SO4, N2. The products were
quantified by GCꢀFID and identified by GCꢀMSD when reference
samples were unavailable. Unless otherwise stated the major byꢀ
products were dimers, e.g. a mixture of dimethyl substituted
biphenyl isomers from toluene. Traces of other compounds, typiꢀ
cally less than 0.5% were sometimes formed. No arene sulfonaꢀ
tion reactions were observed. [a] Three dimethyl benzaldehyde
isomers were formed in similar amounts. [b] The reaction mixture
was kept at ~5 °C for 3 h and then left to warm to ambient temꢀ
perature. [c] The major product, 65ꢀ70%, was 4ꢀ
methylacetophenone. [d] The major byproduct, ~8 %, was benꢀ
zaldehyde. [e] The substrate tended to sublime from the reaction
mixture.
2 H2
Scheme 1. Scheme for the ET-OT oxygenation of ArCH3 to
ArCHO followed by electrolytic release of H2.
Results and Discussion
Oxygenation of ArCH3 to ArCHO. As shown in
Scheme 1, the oxygenation of ArCH3 to ArCHO is a
fourꢀelectron oxidation and since H5PV2Mo10O40 is
nominally a twoꢀelectron oxidant, stoichiometric reacꢀ
tions between H5PV2Mo10O40 and ArCH3 in a 2:1 ratio
were found to be optimal for the formation of ArCHO.
In such a process it has been shown that an oxygen atom
on the surface of the polyoxometalate framework is the
oxygen donor.25 Thus, the ETꢀOT oxygenation of toluꢀ
ene, PhCH3, and various substituted derivatives,
RC6H4CH3 with 2 equivalents H5PV2Mo10O40 was carꢀ
ried out in 50% aqueous H2SO4 as solvent. Depending
on the substrate, the partially optimized conditions of
reaction temperature and time to yield an optimal
amount of ArCHO products are summarized in Table 1.
The results show highly efficient formation of ArCHO in
almost all cases with practically no formation (0ꢀ0.1
Since the reaction is initiated by electron transfer to
•+
yield an electrophilic radical cation, ArCH3 , which can
+
then also yield an electrophilic cation ArCH2 through
further proton and electron transfer, 25 reaction of these
plausible intermediate electrophiles with ArCH3 yields
some small amounts of dimeric compounds, typically as
the only byꢀproducts. 4ꢀNitrotoluene also reacts, howevꢀ
er, in this case sublimation of the substrate leads to its
removal from the reaction mixture lowering the yield.
For moderately activated toluene derivatives, such as the
xylenes, the corresponding tolualdehydes are formed
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selectively. Similarly, 4ꢀtertꢀbutyltoluene reacts selecꢀ transformation. The conversions and product selectivity
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tively to yield the corresponding 4ꢀtertꢀbutyl benzaldeꢀ
hyde with some formation of benzaldehyde likely beꢀ
cause acid catalyzed dealkylation. An interesting subꢀ
strate is 4ꢀisoꢀpropyltoluene, where the tertiary CꢀH
bond is weaker than the primary CꢀH bond. Activation at
the tertiary positions leads to oxygenation coupled with
CꢀC bond cleavage to give the 4ꢀmethylacetophenone as
the main product. Still there are significant amounts of
4ꢀisoꢀpropyl benzaldehyde formed, which is clearly the
kinetically preferred product since at higher temperaꢀ
tures only 4ꢀmethylacetophenone is formed. Similarly,
isoꢀpropylbenzene yielded acetophenone (88 % yield)
and ethylbenzene also yielded the CꢀC bond cleaved
product benzaldehyde (94 % yield). With more electron
donating substituents, for example with 1,2,4ꢀ
trimethylbenzene, dimer formation becomes more proꢀ
nounced. This dimer formation can be significantly inꢀ
hibited by reducing the reaction temperature to 5ꢀ22 °C
and increasing reaction times. This effect is pronounced
in the oxidation of 4ꢀmethoxytoluene where good yields
of 4ꢀmethoxy benzaldehyde were achievable. At 50ꢀ60
°C there was almost only dimerization and even some
formation of oligomers.
were within ±3 % for each cycle.
Alkylarene oxidation can also be carried out electroꢀ
catalytically in one step, that is simultaneous substrate
oxygenation and polyoxometalatate reoxidation. Thus,
10 mmol substrate, 0.23 mmol H5PV2Mo10O40 in 5 mL
50 % H2SO4 were reacted using Pt gauze as working
electrode, and Pt wire as counter and reference electrode
at a cell potential of 1.5 V between the cathode and anꢀ
ode. The higher cell potential was used to accelerate the
reoxidation of the polyoxometalate. When the substrate
was toluene at 70 °C, approximately a 65 % yield (28
turnovers) of benzaldehyde was obtained after 10 h with
>95% selectivity. When pꢀxylene was used as substrate
similar results were obtained. Attempts to use a two half
cell setup as shown in Figure S3 suffered from the lack
of stability of the Nafion membrane at more elevated
temperatures. It should be noted that indirect electrocataꢀ
lytic oxidation of toluene and derivatives is also possible
with Mn3+ and Co3+ salts in concentrated acid, but these
catalysts tend to be less selective to benzaldehyde derivꢀ
atives under high conversion conditions (see discussion
below).29 Ce4+ has been more selective but in order to
obtain good results Ag+ was added as a catalyst or reacꢀ
tions were carried out in CH3SO3H.30
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After completion of the ETꢀOT reaction with the forꢀ
mation of ArCHO, the polyoxometalate is reduced. The
number of electrons on the polyoxometalate was measꢀ
ured by titration with KMnO4 on the representative toluꢀ
ene oxidation reaction. About 1.95 electrons per polyoxꢀ
ometalate were found which is commensurate with the
yield of benzaldehyde and the reaction stoichiometry.
The completion of catalytic cycles in typical organic
solvents is possible by use of O2, equation 1.
Mechanism of activation of ArCH3. The key experiꢀ
mental observation that oxygenation of toluene with
H5PV2Mo10O40 is possible in a mineral acid solvent but
not in an organic solvent such as acetonitrile requires
detailed explanation. It was hypothesized that the strongꢀ
ly acidic medium lead to the increase in the redox potenꢀ
tial of H5PV2Mo10O40. In Figure 1, we present the cyclic
voltammetry measurements that show the changes in the
oxidation potential as a function of H2SO4 concentration.
See Figure S4 for all the cyclic voltammograms. At
increasing H2SO4 concentrations from 0.1ꢀ5% there is a
relatively small change in the oxidation potential from
~0.41 to 0.54 V versus SCE. At concentrations between
10ꢀ25% it was difficult to observe the redox wave, howꢀ
ever at 30% to 50% H2SO4 the oxidation potential clearꢀ
ly and very strongly shifted to 1.0ꢀ1.1 V versus SCE.
This shift in the redox potential is attributed to the forꢀ
mation of a protonated polyoxometalate at higher H2SO4
concentrations (see below).
V
(1) 2 H7PV2IVMo10O40 + O2 → 2 H5PV2 Mo10O40 +
2 H2O
However, in 50 % H2SO4 this reaction is very slow and
alternatively the reduced polyoxometalate can be reꢀ
oxidized by electrolysis with quantitative formation of
H2.27 A cyclic voltametric measurement of the reaction
mixture after the formation of the reduced polyoxometꢀ
alate shows a reversible redox wave at ~ 1.1 V versus
SCE, Figure S1. Therefore, H7PVIVMo10O40 was reoxiꢀ
dized with a Pt gauze anode and a platinum wire cathode
at a potential of 1.3 V or higher between the anode and
cathode to quantitatively release H2, Figure S2.28 It
should be noted that in a twoꢀcell setup with a Nafion
membrane, Figure S3, one visually observe that H2 is
being released at the Pt cathode electrode and that the
reduced green polyoxometalate was oxidized to the orꢀ
ange H5PVVMo10O40 at the anode. In this vein, five oxyꢀ
genation – electrolysis cycles were carried out without
loss of reactivity on three representative substrates, toluꢀ
ene, 4ꢀchlorotoluene and 4ꢀtertꢀbutyltoluene showing
that the catalyst is easily reoxidized and then recovered
without its removal from the solvent in a quantitative
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Figure 1. Oxidation potential, E1/2
,
versus SCE of
Figure 2. Possible initial outerꢀsphere reactions for the oxidation
1
2
3
4
5
6
7
8
H5PV2Mo10O40 at various concentrations of aqueous H2SO4. The
measurements were carried out at 2 mM H5PV2Mo10O40 using a
glassy carbon working electrode, a platinum wire counter elecꢀ
trode and a calomel reference electrode; scan rate 50 mV/sec.
Representative cyclic voltammograms at 1% (insert left) and 50%
(insert right) H2SO4 are shown.
of toluene and the calculated energetics. AN and SA refer to
acetonitrile and sulfuric acid, respectively.
Activation of the reactants through electron transfer
(ET) or proton coupled electron transfer (PCET) usually
precedes oxygen transfer from the polyoxometalate to a
substrate. Figure 2 displays the calculated energetics for
the possible initial outerꢀsphere reactions for the oxidaꢀ
tion of toluene. Although ET presents a plausible initial
step for a neutral complex 1 in acetonitrile and, especialꢀ
ly in sulfuric acid, all the outer sphere reactions of this
complex are endergonic at 298 K. The outerꢀsphere reacꢀ
tions of 2 with toluene are energetically more favorable.
Thus, electron transfer becomes exergonic in sulfuric
acid. In gas phase as well as in the less polar acetonitrile
solution PCET is energetically preferred, although 2 is
not experimentally accessible under these conditions; ET
is still endergonic. Thus, in contrast to PCET in neutral
complexes as observed previously for more reactive
alkylarenes such as xanthene,25 toluene activation in
sulfuric acid presents a sequential protonation of the
polyoxometalate by the solvent followed by electron
transfer and then proton transfer from the substrate to
the polyoxometalate, Scheme 2.
DFT calculations show that the oxidation of PhCH3 to
PhCHO according to Scheme 1 is thermodynamically
favorable with ꢀG298 = ꢀ39.0 and ꢀ36.9 kcal/mol in aceꢀ
tonitrile and sulfuric acids, respectively. It is shown
above that protonation dramatically increased the oxidaꢀ
tion potential and reactivity of H5PV2Mo10O40. This has
also been observed with other oxidants such as mangaꢀ
nese and cobalt acetate,31 and has been attributed (i) to
the lowering of orbital energies including that of the
LUMO, (ii) to an increase of electrophilicity through
formation of a positively charged species and (iii) speꢀ
cifically for H5PV2Mo10O40 by formation of coordinaꢀ
tively unsaturated sites that become available for coorꢀ
dination of a reactant.32 In a nonꢀprotic regime, polyoxꢀ
ometalates such as H5PV2Mo10O40 are neutral where the
negative charge of the polyanion is fully compensated
by the corresponding number of protons chemically
bound to the bridging oxygen atoms, preferably around
vanadium atoms.33,34 In sulfuric acid calculations show
that further protonation of H5PV2Mo10O40 is favorable
with ꢀG298 = ꢀ2.4 kcal/mol, equation 2.
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Scheme 2. Reaction pathways for hydroxylation of xanthene
in acetonitrile (top) and toluene (bottom) in aqueous H2SO4.
(2)
H5PV2Mo10O40 + H3O+
H6PV2Mo10O40+ + H2O
1
2
Moreover, the proton affinity of reduced species is
even higher, Table S1. Thus, protonation favors the reꢀ
duction of this polyoxometalate both kinetically and
thermodynamically. As predicted by the calculations, the
protonation increases the electron affinity or oxidative
“power” of H5PVV Mo10O40 and H6PVVVIVMo10O40 by
2
10.6 kcal/mol and 9.3 kcal/mol, respectively.
Substitution effects. The results from Table 1 clearly
show that toluene derivatives with electron donating
groups are more reactive than those with electron withꢀ
drawing groups. This observation is commensurate with
the calculations presented above showing that activation
of PhCH3 by 2 is initiated by ET. Thus, one might expect
that the rate of oxidation of a series of substrates
RC6H4CH3 for various substituents R would be 4ꢀMe >
H > 4ꢀBr > 4ꢀCl > 4ꢀF. Indeed, the vertical ionization
energy of these compounds, which represents the driving
force for ET, approximated by the HOMO level in sulfuꢀ
ric acid, is appropriate for this order, Table S2. It was,
therefore, initially surprising to observe that in the oxiꢀ
dation of 4ꢀRC6H4CH3 to 4ꢀRC6H4CHO the relative first
order rate constants, Figure S5, were 4ꢀMe (1.24) > H
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Journal of the American Chemical Society
(1.0) > 4ꢀF (0.88) > 4ꢀCl (0.43) > 4ꢀBr (0.24); the relaꢀ
results and as discussed above, after the initial ET reacꢀ
tion to yield PhCH3 , the rate determining step is the
•+
1
2
3
4
5
6
7
8
tive rates of the 4ꢀhalogen substituted compounds are
very noticeably inverted. Further analysis of calculated
data shows that the adiabatic ionization energy, Table
S2, which represents the thermodynamic effect of ET
shows a trend for the halogen substituted compounds
that is proportional to the observed rates. One may raꢀ
tionalize these results by noting that spin delocalization
is the main factor that determines the stability of a benꢀ
zylic radical.35 Thus, spin localization on the electron
withdrawing halogen substituents may lead to destabiliꢀ
zation of the benzylic radical. Indeed, for the isodesmic
reaction, equation 3, we have found that there is a correꢀ
lation between the experimentally observed substituent
induced change in the reaction rate with the computed
stabilization or destabilization energies, Figure 3. Thus,
the radical cation of pꢀxylene is more stable (less reverse
ET) relative to that of toluene leading to a faster rate for
pꢀxylene. On the other hand, the radical cations of 4ꢀ
XC6H4CH3 (X = F, Cl, Br) are less stable (more reverse
ET) than that of toluene, Br < Cl < F. Thus, in the range
of reversible ET the less stable the intermediate radical
cation the slower the rate.
sequential PT reaction leading to formation of the highꢀ
•
est energy intermediates, the benzylic radical PhCH2
and [H7PVIVVVMo10O40]•+ (5); ꢀG‡ = 19.7 kcal/mol.
This is quite comparable to the experimental value of
298
ꢀG‡ = 22.8 kcal/mol (ꢀH‡ = 15.8 kcal/mol; ꢀS‡
298
298
298
= ꢀ23.3 cal/mol K) obtained from the Eyring equation,
Figure S6. In the transition state (TS) the proton being
transferred has short bonds with both the benzylic carꢀ
bon atom (1.25 Å) and a bridging oxygen atom of the
polyoxometalate (1.34 Å). It should be expected that a
PT limiting step would be associated with a kinetic isoꢀ
tope effect (KIE). Indeed, such a measurement, Figure
S7, showed a KIE = 4.95 in a comparative experiment
between the oxidation of C7H8 in H2SO4/H2O and C7D8
in D2SO4/D2O. A competitive experiment using a 1:1
mixture of C7H8 and C7D8 also indicated a similar KIE,
but the GCꢀMS analysis was complicated by competing
HꢀD exchange reactions at both the benzylic and ring
positions.
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•
After the formation of PhCH2 there is a “rebound”
•
where the PhCH2 is bonded to the bridging atom of the
•+
•+
(3) C6H5CH3 + 4ꢀRC6H4CH3 → C6H5CH3 + 4ꢀ
polyoxometalate to form stable triplet and singlet interꢀ
mediates of similar energy (8T and 8S). Subsequently,
proton transfer to the bridging oxygen atom leads to
formation of PhCH2OH still strongly bonded to the polꢀ
yoxometalate, intermediate 9, although the VꢀO/MoꢀO
bonds are considerably elongated to 2.35/2.44 Å from
2.12ꢀ2.14/2.04 Å in 8. Benzyl alcohol is released
through the formation of defect species with coordinaꢀ
tively unsaturated sites and coordination of water (10),
Figure S8, by the scission of a VꢀO/MoꢀO bond. It
should be noted that after short reaction times (20ꢀ30
min) small amounts of benzyl alcohol are indeed obꢀ
served in the GC analyses. Furthermore, separate experꢀ
iments also showed that benzyl alcohol is facilely oxiꢀ
dized to benzaldehyde; relative first order rate constants
PhCH2OH:PhCH3 = 4.9.
RC6H4CH3
Figure 3. Correlation between observed substituent induced
changes in the total reaction rate with computed stabilization (+)
and destabilization (−) energies (ꢁG298 in sulfuric acid, kcal/mol)
relative to toluene cation found using isodesmic reaction (3).
Further in the course of the reaction pathway calculaꢀ
tions show the feasibility of subsequent oxidative dehyꢀ
drogenation of PhCH2OH by another protonated comꢀ
plex 2 initiated by an outerꢀsphere ET, where the proꢀ
pensity for ET is similar to that of PhCH3, Table S2.
However, since the formation of PhCHO does not reꢀ
quire the breaking of MꢀO bonds in the polyoxometꢀ
alate, it proceeds with energies that are overall more
favorable.
Therefore, one may suggest that although the ET from
all the tested para substituted compounds, 4ꢀRC6H4CH3,
is exergonic, radical cation intermediates of low stability
as observed for 4ꢀhalogen substituted compounds may
reverse the ET step and reduce the rate of reaction
measured as formation of product. In contrast, for subꢀ
strates with electron donating groups the benzylic radiꢀ
cal is stable enough to slow or inhibit reverse ET reacꢀ
tions and the total rate of oxidation is mainly determined
by the energy of the HOMO, the driving force for ET
(see also below).
As stated above, contrary to organic solvents where
ETꢀOT oxygenation of toluene does not occur, H2SO4
can react with H5PVV Mo10O40 to yield a protonated,
2
cationic [H6PVV Mo10O40]+ species. Thus, an ET reacꢀ
tion of [H6PVV2Mo10O40]+ with toluene in H2SO4 is
2
favored
compared
to
a
reaction
between
Mechanism of the ET-OT reaction. The proposed calꢀ
culated mechanism for the ETꢀOT oxygenation of toluꢀ
ene is presented in Figure 4. As can be seen from the
H5PVV Mo10O40 and toluene in acetonitrile by 19
2
kcal/mol, in good agreement with the experimentally
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observed increase of the oxidation potential of
Étards reagent, CrO2Cl2,15 and permanganate.16,36 The
ET oxidation of ArCH3 with CoIII(OAc)3 is long
known,37 but the required use of O2 as an oxygen donor
leads to formation of peroxo radicals, ArCH2OO•, and
then alkoxy radicals, ArCH2O•. Especially the latter
easily abstracts a hydrogen atom from benzaldehyde to
promote a competing autoxidation reaction pathway by a
hydrogen atom transfer (HAT) mechanism and forꢀ
mation of ArCOOH. The slow kinetic formation of
CoIII(OAc)3 in aerobic reactions has also led to use of
promotors, notably bromide typically together with
Mn(OAc)2 which further attenuates ArCOOH formation
by autoxidation.38 Thus, it is difficult to obtain high
yields of ArCHO using CoIII(OAc)3/O2. Although, the
1
2
3
4
5
6
7
8
H2PV2Mo10O40 by ~0.7 eV when moving from diluted to
concentrated sulfuric acid, Figure 1. It should be also
noted that the protonation of the polyoxometalate and
therefore inter alia the use of mineral acid solvents leads
to more favorable thermodynamics and kinetics
throughout the reaction profile. Moreover, the total enꢀ
ergy of the reaction is also favored by the protonation of
the polyoxometalate, equation 4.
9
(4) PhCH3 + 2[H6PVV Mo10O40]+ + H2O → PhCHO
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2
+ 2[H8PVIV2Mo10O40]+ ꢀG298 = ꢀ44.5 kcal/mol
PhCH3 + 2 H5PVV Mo10O40 + H2O → PhCHO + 2
2
H7PVIV2Mo10O40 ꢀG298 = ꢀ36.9 kcal/mol
15
The hallmark of the transformation reported here is the
very high selectivity obtained for ArCHO without forꢀ
mation of benzoic acid derivatives, ArCOOH. This is
easily explained by the much less favored ionization
energies and ꢀG298 for ET for PhCHO compared to
PhCH3 and PhCH2OH, Table S2. In this context, it is
also worthwhile to discuss the intrinsic differences and
advantages of ETꢀOT oxidation of PhCH3 with
H5PV2Mo10O40 compared to (a) ET oxidation catalyzed
by CoIII(OAc)3 using O2 as oxygen donor and on the
other hand (b) the use of stoichiometric oxidants such as
stoichiometric oxidation of ArCH3 by CrO2Cl2 or perꢀ
manganate16,36 is long known, the selectivity to ArCHO
is low.15,16 Interestingly, however, Mayer and coworkers
have convincingly argued that these reactions proceed
by a HAT or hydride transfer mechanism concluding that
the key feature in these reactions is affinity of the oxiꢀ
dant to H•/H– that represents the thermodynamic driving
force for oxygen transfer. The mechanism of oxidation
of alkylarenes with CrO2Cl2 or KMnO4 is very different
than that observed here with H5PV2Mo10O40.
Figure 4. A DFT calculation derived mechanism for oxidation of toluene H5PV2Mo10O40 in 50% sulfuric acid. Green – V; black – Mo;
redꢀ O; brown – C; whitish ꢀ H.
Conclusions
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Journal of the American Chemical Society
The transformation of toluene and its derivatives to the
electrode cell configuration consisting of (i) glassy carꢀ
bon working electrode, (ii) a Pt wire counter electrode,
and (iii) a calomel a reference electrode. experiments
were performed at room temperature. The scan rate was
50 mV sec–1. Electrolysis in a one cell configuration was
carried out using (i) Platinum gauze (working electrode),
(ii) a Pt wire (counter electrode), and (iii) Pt (a reference
electrode). The experiments were performed at 25ꢀ80
°C. Electrolysis in a two half cell configuaration was
carried out in presence of Pt gauze as working electrode,
and Pt wire as counter and reference electrode at differꢀ
ent potentials from 1.3 to 1.5 V between the anode and
cathode. The higher the potential the faster is the reoxiꢀ
dation reaction. The two half cells were separated by a
Nafion 212 membrane washed before use with 5% wt
H2O2 and 8% H2SO4 consecutively.
1
corresponding benzaldehyde compounds as presented in
Scheme 1, shows both the ETꢀOT oxidation of the subꢀ
strate and the formation of H2 in a second step to form a
cyclic repeatable process, for the high yield formation of
products with a 100% theoretical atom economy, conꢀ
sidering that H2 has value. The oxidation potential of
H5PV2Mo10O40 in this media, 1.1 V SCE (1.34 V NHE),
is higher than the potential for aerobic formation of waꢀ
ter (1.23 V NHE), equation 1. This prevents the thermal
reꢀoxidation of the reduced polyoxometalate and preꢀ
cludes an aerobic reaction requiring an electrochemical
oxidation of the reduced polyoxometalate. The generalꢀ
ly very high reaction yield lends an important practical
aspect to such a reaction with potential to replace comꢀ
mon nonꢀbenign procedures. Notably, the use of aqueous
H2SO4 as solvent leads to an aqueous biphasic reaction
medium,38 and therefore a simple cascade of operations
– (i) thermal substrate oxygenation, (ii) phase separation
of the organic and catalyst phase and (iii) catalyst recyꢀ
cle and recovery by electrolysis, can be implemented.
However, oneꢀstage electrocatalytic reactions are also
viable. The stability of the Nafion membrane in a two
halfꢀcell configuration at elevated temperatures someꢀ
times needed is a remaining technical issue to be solved.
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Computational method. All computations were done
using the same methodology previously described by us
for calculations involving H5PV2Mo10O40.32 Bulk solꢀ
vent effects of the sulfuric acid medium have been calꢀ
culated at the M06/PC1 level using the continuum solvaꢀ
tion model COSMO with a static dielectric constant, ε =
100.41
ASSOCIATED CONTENT
Supporting Information. Additional experimental inꢀ
formation and data. This material is available free of
charge via the Internet at http://pubs.acs.org.
In summary, the use of strong mineral acids as solvents
that allows significantly improved reactivity due to the
higher redox potential of H5PV2Mo10O40. There are also
advantages in catalyst recovery that are intrinsic to biꢀ
phasic media. Together with the unique ETꢀOT oxygenaꢀ
tion reactions that H5PV2Mo10O40 catalyzes, this reꢀ
search opens up new prospects for selective oxidative
transformations, demonstrated here by the selective
oxygenation of methylarenes.
AUTHOR INFORMATION
Corresponding Author
Email: Ronny.Neumann@weizmann.ac.il
ACKNOWLEDGMENT
This research was supported by the Israel Science Foundation
grants # 1073/10 and 763/14, the Bernice and Peter Cohn Catalyꢀ
sis Research Fund and the Helen and Martin Kimmel Center for
Molecular Design. R.N. is the Rebecca and Israel Sieff Professor
of Chemistry.
Experimental Section
Materials. Alkylarenes were of analytical grade. Deuꢀ
terated compounds were purchased from Cambridge
Isotope Laboratories. H5PV2Mo10O40•32H2O was preꢀ
pared by a known procedure.40
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The carrier gas was Ar, column T = 90 °C.
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