Oxidative C-C bond cleavage of primary alcohols and vicinal diols catalyzed by H5PV2Mo10O40 by an electron transfer and oxygen transfer reaction mechanism

Article abstract of DOI:10.1021/ja8063233

Primary alcohols such as 1-butanol were oxidized by the H₅PV₂Mo₁₀O₄₀ polyoxometalate in an atypical manner. Instead of C-H bond activation leading to the formation of butanal and butanoic acid, C-C bond cleavage took place leading to the formation of propanal and formaldehyde as initial products. The latter reacted with the excess 1-butanol present to yield butylformate and butylpropanate in additional oxidative transformations. Kinetic studies including measurement of kinetic isotope effects, labeling studies with ¹⁸O labeled H₅PV₂Mo₁₀O₄₀, and observation of a prerate determining step intermediate by ¹³C NMR leads to the formulation of a reaction mechanism based on electron transfer from the substrate to the polyoxometalate and oxygen transfer from the reduced polyoxometalate to the organic substrate. It was also shown that vicinal diols such as 1,2-ethanediol apparently react by a similar reaction mechanism. Copyright

Full text of DOI:10.1021/ja8063233

Published on Web 10/09/2008
Oxidative C-C Bond Cleavage of Primary Alcohols and Vicinal Diols
Catalyzed by H
5
PV
2
Mo10
O
40 by an Electron Transfer and Oxygen Transfer
Reaction Mechanism
Alexander M. Khenkin and Ronny Neumann*
Department of Organic Chemistry, Weizmann Institute of Science, RehoVot, Israel 76100
Received August 10, 2008; E-mail: Ronny.Neumann@weizmann.ac.il
The selective oxidation of aliphatic compounds remains a very
difficult but very important research goal. In classic homogeneous
liquid-phase aerobic oxidation, molecular oxygen reacts via the
well-established metal-catalyzed free radical autoxidation pathways
via activation of C-H bonds to yield acids, alcohols, ketones, and
1
hydroperoxides. The product selectivity depends on the catalyst,
the solvent, and the reaction conditions. In the corresponding
autoxidation of primary and secondary alcohols the main products
2
are the corresponding carboxylic acids and ketones. It is known
Figure 1. Polyhedral representation of the five isomers of [PV2Mo10O40]5-
that C-H bonds are more reactive than C-C bonds in free radical
oxidation reactions and oxidation reactions in general, although
C-C bonds have lower bond disassociation energies. This is due
to steric constraints and unfavorable overlap of frontier orbitals
when reactive intermediate species interact with C-C bonds in
(black, MoO ; gray, VO ; white, PO ).
6
6
4
Chart 1. Oxidative Cleavage of Primary Alcohols with
a
H5PV2Mo10O40
3
aliphatic molecules. In fact, little is known about catalytic aerobic
oxidative C-C bond cleavage, although this is a key step in
reactions such as the degradation of the lateral chain of cholesterol
4
by cytochrome P-450. Data on C-C bond cleavage reactions in
alcohol oxidation reactions are limited mainly to oxidative cleavage
of tertiary alcohols by strong oxidants such as concentrated H O
2 2
5
6
7
in sulfuric acid, Cr(VI) and Ce(IV) reagents, metals with
8
9
persulfate, or metal-hydrogen peroxide systems. Recently, it was
also shown that polyethylene glycols and fluorinated alcohols were
oxidatively deformylated by oxygen in the presence of copper salts
and base. C-C bond cleavage in arylalkanol radical cations has
also been reported.
a
Primary alcohol (1 M), H5PV2Mo10O40•34H2O (60 mM) in sulfolane
at 80 °C for 5 h under argon. The products were formed in a 1:1 ratio and
were the only products observed by GC. Identification was by GC-MS and
with reference standards.
1
0
1
1
A survey of the earlier research on liquid phase aerobic catalytic
oxidation reactions mediated by phosphovanadomolybdates of the
reactions, known in high temperature gas phase oxidations as
(3+x)-
Keggin structure, [PV
shows that the [PV
x
Mo12-x
O
40
]
particularly for x ) 2,
17
Mars-van Krevelen reactions, are rare under low temperature
5
-
Mo10
O
40
]
polyoxometalate, Figure 1, cata-
16
2
homogeneous reaction conditions.
lyzed oxidative dehydrogenation reactions through an electron
transfer oxidation of a substrate by the polyoxometalate that is then
Here we present our study on the oxidative carbon-carbon bond
cleavage reaction of primary alcohols by the acidic H PV Mo10O
5 2 40
and show that they appear to proceed by an ET-OT reaction
mechanism. This is an atypical oxidation of alcohols. By corollary,
we show that vicinal diols are oxidized by a similar mechanism.
1
2
reoxidized by oxygen. Typically, free radical autoxidation reac-
5
-
tions are inhibited by [PV
genation reactions catalyzed by [PV
reported, notably including the oxygenation of inorganic sulfur
2 40
Mo10O ] . In parallel, aerobic oxy-
5
-
2
Mo10
O
40
]
have also been
Primary alcohols were reacted with H
5
PV
dioxotetrahydrothiophene (sulfolane) under strictly anaerobic
Schlenk) conditions to yield the products presented in Chart 1 in
2
Mo10
O
40 ·34H
2
O in
13
1
8
compounds and thioethers, the oxidative cleavage of vicinal diols
14
15
to carboxylic acids, and the oxidative cleavage of ketones. Very
little is understood about the mechanism of these reactions although
Br e´ geault and co-workers suggested that vicinal diols were cleaved
via a ternary complex between the polyoxometalate, dioxygen, and
the diol that leads to simultaneous C-C and O-O bond cle-
(
a 1:1 ratio. The polyoxometalate was reduced. Secondary and
tertiary alcohols were dehydrated under these reaction conditions
yielding the corresponding alkenes and no C-C bond cleaved
products.
14b
avage. Additionally, several years ago we reported that activated
arene and alkylated arene substrates such as anthracene and
xanthene were aerobically oxygenated to the corresponding an-
thraquinone and xanthone via a mechanism that involved electron
transfer from the substrate to the polyoxometalate followed by
oxygen transfer from the reduced polyoxometalate to the organic
One may note from these reactions that in all cases there was a
C -C bond cleavage reaction, the products of which may react
R
ꢀ
with the excess primary alcohol to yield the compounds noted in
Chart 1 (see below for full explanation). Since the reactions were
carried out under anaerobic conditions one may assume the new
oxygen atoms in the products originated from H
5 2
PV Mo10O40. This
1
6
substrate. These electron and oxygen transfer (ET-OT) type
was indeed verified in two cases. Thus, the reaction of dehydrated
1
4474 9 J. AM. CHEM. SOC. 2008, 130, 14474–14476
10.1021/ja8063233 CCC: $40.75  2008 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Pathway for the Oxidation of 1-Butanol by
H5PV2Mo10O40 via an ET-OT Mechanism
Figure 2. Arrhenius plot for the oxidation of 1-butanol (500 mM) by
H5PV2Mo10O40 ·34H2O (2.5 mM) in sulfolane under argon. (Insert) Plot of
the observed rate constant as a function of the concentration of
H5PV2Mo10O40 (500 mM 1-butanol, 0.9-2.5 mM H5PV2Mo10O40 ·34H2O,
8
0 °C, in sulfolane under argon).
Scheme 2. Pathway for the Formation of Isochroman
(
3,4-Dihydro-1H-benzo[c]pyran)
C
ꢀ
γ δ
, C , and C carbon atoms shows two new additional peaks at
6
5.8 and 30.3 ppm attributable to peaks related to the interaction
2
0
R ꢀ
of the polyoxometalate C and C atoms. The peaks attributable
γ δ
to the C and C carbon atoms remain unchanged. One may also
observe that the peaks of the sulfolane solvent are also partially
shifted downfield presumably due to protonation of sulfolane by
1
3
5 2 40
the acidic H PV Mo10O .
The observed experimental information can be used to formulate
a possible reaction mechanism for the observed C-C cleavage
Figure 3. C NMR spectra of 1-butanol in sulfolane-d8 (top) and after
addition of 0.33 equiv of H5PV2Mo10O40 ·34H2O and heating for 3 h at 50
°
C (bottom).
5 2
reaction. Initially, H PV Mo10O40 reacts with 1-butanol to yield a
1
8
H
5
PV
2
Mo10
O
40 (∼50% enrichment) with 1-butanol under the
polyoxometalate-substrate prerate determining complex as sup-
1
8
13
conditions described in Chart 1 yielded 1-butylformate (41% O)
and 1-butylpropionate (50% O) as determined by GC-MS. No
doubly labeled products were observed. Similarly oxidation of
ported by the C NMR spectrum, Scheme 1. In this context, we
1
8
also observed that 2,2-diphenyl ethanol and 2,2-dimethyl-1-propanol
were unreactive (only a trace amount of product formed) likely
due to the steric bulk of the polyoxometalate. It should also be
noted that dehydration of 1-butanol to give 1-butene apparently
does not occur since 1-butene was not sampled in either the gas or
liquid phase; 1-alkenes did not undergo C-C bond cleavage.
1
8
2
-methy-1-propanol with H
5
PV
2
Mo10
O
40 yielded acetone (49%
O) and isobutylformate (39% O). Kinetic isotope effect experi-
ments in competitive reactions also under the conditions described
in Chart 1 between 1-butanol/1-butan-1,1-d -ol, 1-butanol/1-butan-
-ol, and 1-butanol/1-butanol-d10 all showed k /k values of
.0 ( 0.1 as measured by GC/MS indicating that C-H bond
18
18
2
1
8
2
,2-d
2
H
D
Since the protonated 1-butanol is long-lived it is likely that
O
1
8
1
exchange occurs with the O labeled polyoxometalate since the
latter is very susceptible to such exchange with water (from
protonated 1-butanol). In the rate determining reaction step electron
and oxygen transfer leads to the cleavage of the C-C bond as
supported by the absence of kinetic isotope effects in reactions
carried out with the various deuterated 1-butanol substrates. In all,
this is a two-electron oxidation coupled with oxygen transfer and
the release of two protons and can be defined as an ET-OT
reaction. The formation of the aldehyde(s) is supported by benzal-
dehyde formation in the oxidation of 2-phenylethanol and acetone
formation in the oxidation of 2-methyl-1-propanol (Chart 1).
Formaldehyde formation is also supported by the formation of
isochroman in the oxidation of 2-phenylethanol (see below).
The formation of the observed and final product may be through
either acid catalyzed formation of a hemiacetal followed by
oxidation via hydrogen abstraction or proton coupled electron
transfer (pathway A). Alternatively, the aldehyde may be first
oxidized to the corresponding carboxylic acid followed by esteri-
fication (pathway B). There is no clear-cut evidence for either
possibility although the formation of isochroman, Scheme 2, can
be best explained by an intramolecular electrophilic aromatic
substitution reaction via an intermediate hemiacetal; no formate
ester of 2-phenylethanol was observed. Pathway A is preferred.
cleavage is not involved in the rate determining step.
The kinetics of the reaction of H PV 40 with excess
-butanol was studied by following the reduction of the polyoxo-
metalate by UV-vis spectroscopy under anaerobic conditions. Thus,
.5 M 1-butanol, 0.9-2.5 mM H PV 40 in sulfolane were
reacted at 80 °C. A log kobs versus log [H 40] plot, Figure
, insert, gave a slope of 0.972 indicating that the reaction is first
5
2
Mo10O
1
0
5
2
Mo10O
5
2
PV Mo10O
2
order in the polyoxometalate. Measurement of rates as a function
of temperature, Figure 2, yielded the following values for the
activation energy, enthalpy, entropy, and free energy of activation:
‡
‡
∆E ) 11.2 kcal/mol, ∆H 338 ) 10.5 kcal/mol, ∆S 338 ) -47.2
a
-1 -1 ‡
cal mol
K
, ∆G 338 ) 26.4 kcal/mol. The high negative value
of ∆S suggests that the transition state of the rate determining
‡
step reaction is highly organized and solvation of the transition
19
state by polar solvent molecules (sulfolane) may also be involved.
To obtain additional evidence on the interaction of H PV
40 and 1-butanol, C NMR spectra were measured in
sulfolane-d . In Figure 3 one may observe the spectrum of 1-butanol
Figure 3, top) and the spectrum after heating the alcohol for 3 h
at 50 °C (no esters formed; GC) under argon in the presence of
5
2
-
1
3
Mo10
O
8
(
0
.33 equiv of H
5 2
PV Mo10O40 (Figure 3, bottom). The spectrum of
1
-butanol with peaks at 61.4, 34.8, 18.8, and 13.8 ppm for the C
R
,
J. AM. CHEM. SOC. 9 VOL. 130, NO. 44, 2008 14475

C O M M U N I C A T I O N S
tion, and the Kimmel Center for Molecular Design. R.N. is the
Rebecca and Israel Sieff Professor of Organic Chemistry.
Supporting Information Available: Full experimental details and
the results of kinetic experiments. This material is available free of
charge via the Internet at http://pubs.acs.org.
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activation: ∆E
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(
1
(
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2
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PV
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O40 in an atypical
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R
ꢀ
13
(18) Sulfolane is a solvent with a high dipole moment and dielectric constant.
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(acetonitrile, nitromethane, NMP, THF) for this C-C bond cleavage
reaction.
posed ET-OT mechanism as supported by C NMR evidence and
kinetic and labeling experiments. The initial carbonyl products
formed further react with the alcohol substrate to yield esters via
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(
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(
3
20) A similar experiment with H PW12O40 and 1-butanol showed quite different
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oxidation.
Acknowledgment. The research was supported by the German-
Israeli Project Cooperation (DIP-G7.1), the Israel Science Founda-
JA8063233
1
4476 J. AM. CHEM. SOC. 9 VOL. 130, NO. 44, 2008