Conversion of levulinate into succinate through catalytic oxidative carbon-carbon bond cleavage with dioxygen

Article abstract of DOI:10.1002/cssc.201300325

Grand Cleft Oxo: Levulinate, available from biomass, is oxidized into succinate through manganese(III)-catalyzed selective cleavage of C-C bonds with molecular oxygen. In addition to levulinate, a wide range of aliphatic methyl ketones also undergo oxidative C-C bond cleavage at the carbonyl group. This procedure offers a route to valuable dicarboxylic acids from biomass resources by nonfermentive approaches. Copyright

Full text of DOI:10.1002/cssc.201300325

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J. Liu, Z. Du, T. Lu, J. Xu*
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Conversion of Levulinate into
Succinate through Catalytic Oxidative
CarbonÀCarbon Bond Cleavage with
Dioxygen
Grand Cleft Oxo: Levulinate, available
from biomass, is oxidized into succinate
through manganese(III)-catalyzed selec-
tive cleavage of CÀC bonds with molec-
ular oxygen. In addition to levulinate,
a wide range of aliphatic methyl ke-
tones also undergo oxidative CÀC bond
cleavage at the carbonyl group. This
procedure offers a route to valuable di-
carboxylic acids from biomass resources
by nonfermentive approaches.
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DOI: 10.1002/cssc.201300325
Conversion of Levulinate into Succinate through Catalytic
Oxidative CarbonÀCarbon Bond Cleavage with Dioxygen
Junxia Liu,[a, b] Zhongtian Du,[a] Tianliang Lu,[a, b] and Jie Xu*[a]
Making full use of oxygen atoms in carbohydrates and its de-
rivatives to produce oxygenated chemicals is an attractive
prospect.[1] The well-known biological production of organic
acids from carbohydrates usually involves CÀC bond cleavage
and release of CO2.[2] Nowadays, chemists are interested in ob-
taining valuable organic acids from biomass resources by
using nonfermentive approaches[1,3] such as catalysis, which
has proven effective in the petrochemical industry. For exam-
ple, lactate can be obtained through selective CÀC bond cleav-
age of sugars.[3a]
In essence, the oxidation of levulinate into succinate in-
volves a selective CÀC bond cleavage of methyl ketone. Satu-
rated ketones are generally resistant to oxidation, and strong
oxidizing agents, such as nitric acid, are still widely used.[8]
Catalytic oxidative CÀC bond cleavage of ketones, especially
unactivated aliphatic ones, with dioxygen is rather challenging.
Thus, the oxidation of levulinate with dioxygen would be both
an interesting fundamental organic transformation as well as
an interesting method of biomass conversion.
Oxidative CÀC cleavage of levulinate at the carbonyl group
requires CÀC bond fission and CÀO bond formation. Inspired
by previous reports on CÀC bond cleavage of oxygen-contain-
ing compounds such as a-hydroxy ketones and vicinal diols,[9]
we envisioned that oxygenation of the CÀH bond adjacent to
the carbonyl group would facilitate CÀC bond fission. Owing
to its electronic structure, there have been several reports on
hydrogen abstraction reactions by stoichiometric and catalytic
amounts of MnIII species.[10] On the basis of these reports, we
describe herein MnIII-catalyzed oxidative CÀC bond cleavage of
levulinate into succinate with dioxygen under mild conditions.
Methyl levulinate was selected as substrate and the oxida-
tion products were determined after catalytic esterification,
which was convenient for analysis (Scheme 2). When the reac-
tion was performed with 5 mol% Mn(OAc)3·2H2O under
Succinic acid is an important chemical for the production of
1,4-butanediol, g-butyrolactone, tetrahydrofuran, and pyrroli-
done. Its derivative poly(butylene succinate) (PBS) is a promis-
ing biodegradable polyester.[4] Succinate can be obtained
through the fermentation of sugars,[2,4] and through the cata-
lytic conversion of (petroleum-derived) maleic anhydride.[4]
Herein, we describe a synthesis of succinate through chemical
methods, using carbohydrates as raw material.
Levulinate has been identified as a key platform molecule in
biorefineries.[5] It can be easily obtained from carbohydrates
such as glucose, fructose, sucrose, starch, and cellulose.[5,6]
Levulinate contains both carbonyl and carboxyl functional
groups, similar to the structure of succinate. Selective oxidative
CÀC cleavage of levulinate at the methyl adjacent to the car-
bonyl group generates succinate (Scheme 1). Although this
transformation has been anticipated in several Review arti-
cles,[5] only a few research reports describe this reaction, and
further development is required using molecular oxygen as ox-
idant under mild reaction conditions.[7]
Scheme 1. Selective oxidation of levulinate into succinate.
Scheme 2. Oxidation products of levulinate after esterification. The C1–C4
labels refer to the number of carbon atoms, excluding the methoxy group.
[a] J. Liu,+ Z. Du,+ T. Lu, Prof. Dr. J. Xu
Dalian National Laboratory for Clean Energy
State Key Laboratory of Catalysis
0.5 MPa oxygen in acetic anhydride, about 95.3% methyl levu-
linate (1) was converted within 10 h at 908C (Table 1, entry 2).
Oxidation products ranging from C1 to C4 were detected, indi-
cating that both CÀC bonds adjacent to the carbonyl group
(a1 and a2) were cleaved (Scheme 2). Ideally, the total
amounts of succinate/CO2 and malonate/acetate should be ap-
proximately equal, if the oxidative cleavage occurs at the a1
and a2 positions with comparable probability. However, succi-
nate (2) was detected as the main product with a yield of
58.6%; much higher than the yield of C3 (3+4) products
Dalian Institute of Chemical Physics, Chinese Academy of Sciences
Dalian 116023 (PR China)
E-mail: xujie@dicp.ac.cn
[b] J. Liu,+ T. Lu
University of the Chinese Academy of Sciences
Beijing 100049 (PR China)
[+] These authors contributed equally to this work.
Supporting Information for this article is available on the WWW under
http://dx.doi.org/10.1002/cssc.201300325.
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indicating that homogenous MnIII catalysts are preferred for
this transformation. In previous reports, vanadium compounds
have proved effective for catalytic CÀC bond cleavage of a-hy-
droxy ketones and vicinal diols,[9] however, dimethyl succinate
yields of only 1.0% and 10.2% were reported over
H5PV2Mo10O40 and VO(acac)2, respectively. Moreover, the use of
ferric nitrate, copper acetate, and cobalt(II) acetate resulted in
much lower conversions under similar reaction conditions (see
Figure 1). Thus, the homogenous MnIII compounds offer
a unique advantage in the catalytic selective oxidative CÀC
cleavage of levulinate at the a1-position.
Table 1. Catalytic oxidation of levulinate with dioxygen as oxidant.[a]
Entry
Catalyst
Conv.
[mol%]
Yield of important diesters[b]
[mol%]
2
3+4
5+6
1
2
3[c]
4
none
trace
95.3
2.4
92.4
12.9
88.8
1.1
n.d.
58.6
0.1
49.8
7.7
52.4
0.3
n.d.
2.5
2.3
2.9
0.7
3.2
0.4
0.8
1.0
n.d.
10.6
n.d.
14.1
4.4
16.6
0.4
0.6
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(acac)3
Mn(OAc)2·4H2O
Mn(OAc)2·4H2O
MnO2
5
6[d]
7
8
9
Mn2O3
Mn3O4
2.7
1.9
0.6
0.3
Important issues in this transformation are the formation
0.4
[a] Reaction conditions: methyl levulinate (2.5 mmol), catalyst (5 mol%
Mn), acetic anhydride (2 mL), T=908C, P=0.5 MPa O2, t=10 h; n.d.=no
detection. [b] Yield of important diesters after esterification, others prod-
ucts were mainly acetate and CO2. [c] N2 atmosphere. [d] Reaction time
20 h.
(2.5%). Moreover, the yield of C2 diesters, including dimethyl
oxalate and methyl dimethoxyacetate (5+6), was about
10.6%. Methyl acetate was also generated through catalytic
oxidation. This was confirmed by using another solvent (meth-
anol) instead of acetic anhydride (Scheme S2). In addition to
the esters in the liquid phase, CO2 was also detected in the
gas phase. The amount of CO2 was higher than that of succi-
nate (87%, based on the amount of levulinate). On the other
hand, no oxidation product was observed when the reaction
was performed without catalyst (entry 1). A control experiment
under N2 revealed that most of methyl levulinate remained
intact (entry 3). Hence, manganese(III) acetate proved effective
for the catalytic oxidative CÀC cleavage of methyl levulinate
into succinate with molecular oxygen as oxidant, and selective
cleavage of the CÀC bond mainly occurred at the a1-position.
To the best of our knowledge, this is the first report on the
conversion of levulinate into succinate, catalyzed by manga-
nese compounds, with molecular oxygen as oxidant under
mild conditions. Although the yield of succinate should be im-
proved further, this is the best result achieved so far for this
challenging transformation.
Figure 1. Oxidation of methyl levulinate with different transition-metal com-
pounds. Reaction conditions: methyl levulinate (2.5 mmol), 5 mol% catalyst
(H5PV2Mo10O40 based on vanadium), acetic anhydride (2 mL), T=908C,
P=0.5 MPa O2, t=10 h.
pathway of the oxidation products and the amount of carbon
dioxide released; more than the theoretical value. Cleavage of
the CÀC bond could occur inevitably at both sides adjacent to
the carbonyl group (Scheme 3, a1 and a2 position). CÀC bond
cleavage at the a1-position gives carbon dioxide and a C4
product. At the same time, CÀC cleavage at the a2 position
leads to the formation of acetic acid and C3 compounds such
as malonate in the beginning. Malonate is known to easily de-
We continued our study by fo-
cusing on the yields of the im-
portant diesters, including the
succinate, malonate, and oxalate
ones (Table 1). Similar results
were obtained when Mn(acac)3
was used (entry 4). However,
when Mn(OAc)2·4H2O was used,
the conversion of methyl levuli-
nate was only 12.9% within 10 h
after an induction period of ca.
300 min (entry 5). Nevertheless,
when the reaction time was ex-
tended to 20 h, the conversion
of methyl levulinate reached
88.8% (entry 6). In contrast,
manganese oxide (entries 7–9)
exhibited a rather low activity, Scheme 3. Formation pathways for the main products of methyl levulinate oxidation.
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compose into acetic acid and CO2. We tested the stability of
different diesters under the reaction conditions (Table S2).
When dimethyl succinate and dimethyl oxalate were tested,
about 95.6% and 98.8% was recovered, respectively. In con-
trast, when dimethyl malonate was tested less than 5% was re-
covered, and oxalate, dimethoxyacetate, oxomalonate, and
CO2 were detected. These results are in good agreement with
the inherent properties of malonate, and the observed low
yield of malonate as well as the increase of CO2. Meanwhile,
oxidation of the active methylene group gave oxomalonate,
which led to the formation of C2 products such as oxalate. The
complete proposed reaction pathway is shown in Scheme 3.
The loss of C3 products, the formation of oxalate, and in-
creased amount of carbon dioxide are closely related to the
unique structure of levulinate, and this is why selective oxida-
tion of levulinate into succinate is rather challenging.
Another key issue is transfer of the oxygen atom, from OÀO
to CÀO during the oxidative CÀC bond cleavage. Previous
studies on MnIII-catalyzed reactions proposed that hydrogen
abstraction occurs by enolization of the ketone.[10] This inter-
pretation is in agreement with our experimental observations.
For example, in the oxidation of 2,2-dimethyl-3-hexanone
(entry 7), the are hydrogen atoms at only one side adjacent to
the carbonyl group. Thus, enolization can occur at only one
side, as can the subsequent CÀC cleavage.
Valence variation of manganese was also studied by UV/Vis
spectroscopy. When chelated with H3PO4, the MnIII complex
showed a maximum absorption at approximately l=510 nm,
while the MnII species did not show this peak (Figure S10).[12]
After Mn(OAc)3·2H2O was stirred with methyl levulinate under
an atmosphere of N2 at 908C, the MnIIIabsorption band disap-
peared. This result is consistent with the above-mentioned hy-
drogen abstraction. Moreover, when 5 mol% 2,6-di-tert-butyl-
p-cresol (BHT) was added during the oxidation of methyl levuli-
nate, the reaction was completely impeded. This indicates that
a free radical process is involved at the beginning.
Generating carboxyl groups through oxidative CÀC bond
cleavage is useful from both academic and industrial perspec-
tives, especially when using dioxygen as oxidant.[11] Besides
methyl levulinate, the substrate scope was investigated with
manganese(III) acetate as catalyst (Table 2). When 2-pentanone,
2-hexanone, 2-octanone, and 2-nonanone were oxidized, the
main products were also derived from cleavage of the CÀC
After hydrogen abstraction by MnIII from the CÀH bond adja-
cent to the carbonyl group, reaction of monoketones with
MnIII gave acetoxy ketones in the absence of oxygen.[13] In con-
trast, the formation of organic
Table 2. Oxidative CÀC bond cleavage of aliphatic ketones with dioxygen.[a]
peroxide would be inevitable in
the presence of oxygen (Fig-
Entry
Substrate
Conv.
[%]
Main products
ure S6). We terminated the oxi-
dation halfway by destroying the
1
2
3
4
5
6
7
8
2-pentanone
2-hexanone
2-octanone
2-nonanone
5-chloro-2-pentanone
4-methyl-2-pentanone
2,2-dimethyl-3-hexanone
4-nonanone
97
>99
>99
>99
>99
>99
45
butyrate (79%), propionate (21%)
pentanoate (72%), butyrate (20%)
heptanoate(69%), hexanoate (20%)
octanoate (67%), heptanoate (21%)
4-chlorobutyrate (76%), 3-chloropropionate (14%)
3-methylbutyrate (85%), 2-methylpropionate (15%)
2,2-dimethylpropionate+propionate (100%)
hexanoate+propionate(46%) pentanoate+butyrate (54%)
catalyst with water. The colorless
solution obtained was able to
change the color of an aqueous
KI/starch solution. Furthermore,
it could oxygenate Ph3P into tri-
phenylphosphine oxide at room
temperature. When 18O2 was
used instead of ordinary oxygen,
18O-enriched triphenylphosphine
oxide was formed (Figures S7
and S8). This suggests that per-
84
[a] Reaction conditions: ketones (2.5 mmol), Mn(OAc)3·2H2O (5 mol%), acetic anhydride (2 mL), T=908C, P=
0.5 MPa O2, t=10 h; [b] Corresponding methyl esters after esterification. The other products are mainly CO2
and acetate.
bond between methyl and carbonyl. The ratio of CÀC bond fis-
sions at the corresponding methyl and methylene position was
approximately 3–4 (entries 1–4). 5-Chloro-2-pentanone could
also be transformed smoothly, with 99% conversion and a simi-
lar product ratio, and the halide substituent was still present
after the reaction (entry 5). Moreover, branched-chain aliphatic
ketones could also be converted under the same reaction con-
ditions (entries 6 and 7). The oxidative cleavage occurred on
only one side, with 100% selectivity to 2,2-dimethyl propio-
nate+propionate when 2,2-dimethyl-3-hexanone was oxi-
dized. In contrast, when 4-nonanone was used as substrate,
the ratio of hexanoate+propionate was roughly that of penta-
noate+butyrate (entry 8). Hence, a wide range of unactivated
linear aliphatic ketones could smoothly undergo MnIII-catalyzed
oxidative CÀC bond cleavage at the carbonyl group with mo-
lecular oxygen as oxidant. The CÀC cleavage occurs preferen-
tially between the carbonyl and methyl groups when methyl
ketones are used.
oxides are formed during the oxidation. The preparation of
stable peroxides by MnIII catalysts at low temperature also
agrees with this result.[14] These results indicate that oxygen
atoms are transferred from dioxygen to the substrate via a per-
oxide.
Decomposition of peroxide is known to occur in the pres-
ence of manganese ions. This decomposition may generate
oxygen-functionalized ketones, such as a-dicarbonyls. To test
this hypothesis, we selected 2,3-heptanedione as a model
compound (Table S3 and Figure S9). 2,3-Heptanedione could
be converted into pentanoate and butyrate smoothly through
catalytic oxidation with dioxygen. Reaction of 2,3-heptane-
dione with 1.0 equiv Mn(OAc)3·2H2O under nitrogen atmos-
phere also gave pentanoate (53% conversion, 100% selectivi-
ty). In the same reaction conditions, 1.0 equiv Mn(OAc)2·4H2O
failed to convert 2,3-heptanedione. These results suggest a-di-
carbonyl CÀC bond cleavage by MnIII, even in the absence of
oxygen.[15] Based on these results, we propose that peroxide
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