Highly selective one-step dehydration, decarboxylation and hydrogenation of citric acid to methylsuccinic acid

Article abstract of DOI:10.1039/c6sc04541c

The one-step dehydration, decarboxylation and hydrogenation of the bio-based and widely available citric acid is presented. This reaction sequence yields methylsuccinic acid with yields of up to 89%. Optimal balances between the reaction rates of the different steps were found by varying the hydrogenation catalyst and the reaction parameters (H₂ pressure, pH, temperature, time and catalyst-to-substrate ratio).

Full text of DOI:10.1039/c6sc04541c

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Highly selective one-step dehydration, decarboxylation and
hydrogenation of citric acid to methylsuccinic acid
Jasper Verduyckta and Dirk E. De Vosa
Received 00th January 20xx,
Accepted 00th January 20xx
The one-step dehydration, decarboxylation and hydrogenation of the bio-based and widely avalaible citric acid is
presented. This reaction sequence yields methylsuccinic acid with yields up to 89%. Optimal balances between the
reaction rates of the different steps were found by varying the hydrogenation catalyst and the reaction parameters
(H2 pressure, pH, temperature, time and catalyst-to-substrate ratio).
DOI: 10.1039/x0xx00000x
www.rsc.org/
was reacted at 225°C for 6 h in water (Table 1, entries 1-4).
These initial reaction conditions were inspired by the
decarboxylation of L-proline to pyrrolidine, which was recently
Introduction
Methylsuccinic acid constitutes a very interesting bio-
based building block for the chemical industry. This
bifunctional carboxylic acid is used for the production of
biodegradable polyesters,1–4 binders,5 and cosmetics.6
Currently, it is only available via the hydrogenation of itaconic
acid.7–9 Research is still being conducted to optimise this
transformation.10 Itaconic acid itself is synthesised via
fermentation with an annual production volume of 41.4
thousand tons in 2011.11
Citric acid is a much more widely available renewable
resource. It is produced via a high yield fermentation with an
annual production volume of 2 million tons in 2016.12 Sanders
and co-workers recently reported the use of citric acid as a
platform chemical for the synthesis of methacrylic acid.13 The
reported by our group.14 In addition, NaOH was added in order
to reduce unwanted side reactions, such as hydration of the
generated double bond.13 In general, citric acid is very
reactive; full conversions are readily obtained in all reactions.
Scheme 1 gives an overview of the different products
observed via 1H-NMR. Citric acid (
1) is first dehydrated to
aconitic acid, which can spontaneously decarboxylate under
the reaction conditions (Table 1, entry 25).15 Although this
reaction proceeds spontaneously, it is also accelerated by
metal catalysts based on e.g. Pd or Pt.13 The catalyst support
(at least in case of BaSO4) appears to have no influence on the
reaction (Table 1, entry 26). Via this first decarboxylation,
itaconic acid (
carboxylic acid can quickly isomerise to mesaconic (
citraconic acid (
).15 In the presence of H2 these isomers can
either be hydrogenated to the desired methylsuccinic acid (
or further decarboxylated to methacrylic ( ) and crotonic acid.
Hydrogenation of the latter then leads to the formation of
isobutyric and butyric acid ), respectively. The
2
) is formed (Scheme 2).15,16 This unsaturated
) and
3
dehydration of citric acid was followed by
a double
4
decarboxylation, catalyzed by Pd/Al2O3; this reaction sequence
resulted however in a selectivity of only 41% at full conversion
with 44% selectivity to volatile degradation products.
In this edge article we present the one-step dehydration,
decarboxylation and hydrogenation of citric acid. This surprising
reaction sequence was discovered by performing the
decarboxylation reaction under a low H2 pressure in the presence of
Pd and allows to obtain methylsuccinic acid in very high yield.
5
)
6
(
7
)
(8
monofunctional unsaturated carboxylic acids can also react
through a third consecutive decarboxylation, yielding propene,
which is hydrogenated to propane
(9) in a H2-rich
environment. The presence of lower alkanes like propane (
9
)
leads to mass loss from solution and was confirmed by
performing gas phase Fourier transform infrared spectroscopy
(FTIR) on the headspace of the reaction in entry 9. When
hydrogenation of the double bond occurs before the first
decarboxylation, propane-1,2,3-tricarboxylic acid (10) can be
obtained. Finally, acetone (11), pyruvic (12) and acetic acid
Results and discussion
In the initial proof of concept, Pd/C, a well-known
hydrogenation catalyst, was compared to Pt/C under an inert
atmosphere as well as under a H2-rich atmosphere; citric acid
(13) were observed as fragmentation products (cfr. infra). The
detailed identification of the observed (numbered) compounds
is given in the ESI. The identity of the desired methylsuccinic
a.Centre for Surface Chemistry and Catalysis, Department of Microbial and
Molecular Systems, KU Leuven – University of Leuven, Leuven Chem&Tech,
Celestijnenlaan 200F, Post Box 2461, 3001 Heverlee, Belgium.
acid
(5) was additionally confirmed by GC-MS after
derivatisation with methanol to dimethyl methylsuccinic acid.
Electronic Supplementary Information (ESI) available: experimental details,
catalyst characterisation, time course, PH2 optimisation for 0.5 mol% Pd, isotopic
labelling experiment and product identification. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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In the first reactions,
a
substantial amount of isobutyric acid (
7
) are formed. In these reactions H2 most likely
View Article Online
DOI: 10.1039/C6SC04541C
methylsuccinic acid (5, 67%) was only formed in the presence originates from CO via the water-gas shift reaction, which
of Pd/C and under a H2-rich atmosphere (Table 1, entry 4). occurs readily under the reaction conditions.14 CO itself is
Using Pt/C the hydrogenation was rather slow, resulting in only formed during the fragmentation of citric acid (
1, cfr.
31% selectivity for methylsuccinic acid (
5
;
Table 1, entry 2). infra).13,15 In addition, in the absence of H2 2-hydroxyisobutyric
Although hydrogenated products were observed in the acid is formed with a selectivity of 12% (Table 1, entry 3). This
reactions without added H2, hydrogenation is not fast enough side product most probably stems from the hydration of
to suppress the formation of further decarboxylation products; mesaconic or citraconic acid
(3-4), followed by
non-reduced Pd or Pt species at the surface of the metal decarboxylation. The hydration of methacrylic acid (
6
) is not
particles might facilitate the radical fragmentation (cfr. infra; likely, since one would expect the formation of
Table 1, entries 1, 3). Especially acetic (13), methacrylic (6) and 3-hydroxyisobutyric acid.17,18
a
Table 1. Decarboxylation of citric acid in the presence or absence of H2
.
Selectivity [%]
C/S b
[mol%] [bar] [°C]
PH2
T
t
[h]
Additive
(eq.)
Conversion
[%]
Itaconic
Catalyst
MSA c PTA d
2nd deca e
Fragmentation f
isomers g
1
2
3
4
5
6
7
8
9
Pt/C
Pt/C
Pd/C
Pd/C
Pd/ZrO2
Pd/MgAl2O4
Pd/BaSO4
Pd/Al2O3
Pd/BaSO4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
0 h
225
225
225
225
225
225
225
225
225
225
225
225
225
225
175
200
250
175
225
225
225
225
225
225
225
225
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
0.67
0.67
0.67
0.67
0.67
0.67
0.67
6
NaOH (0.8)
NaOH (0.8)
NaOH (0.8)
NaOH (0.8)
NaOH (0.8)
NaOH (0.8)
NaOH (0.8)
NaOH (0.8)
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
12
>99
>99
>99
>99
>99
>99
>99
>99
23
31
13
67
81
71
81
71
75
75
74
84
64
54
82
83
58
67
86
84
77
36
68
89
<1
<1
<1
<1
<1
2
<1
7
<1
<1
<1
<1
4
<1
<1
<1
7
28
23
46 i
12
7
5
3
14
5
6
3
3
4
2
1
1
10
<1
3
16
9
27
7
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
17
<1
<1
33 l
32 l
4
0 h
4
4
4
4
4
4
8
12
4
4
4
4
4
4
4
4
6
12
10
9
8
9
15
7
18
26
5
5
9
<1
6
7
NaOH (1.0)
NaOH (1.0)
NaOH (1.0)
10 Pd/BaSO4
11 Pd/BaSO4
12 Pd/BaSO4
13 Pd/BaSO4
14 Pd/BaSO4
15 Pd/BaSO4
16 Pd/BaSO4
17 Pd/BaSO4
18 Pd/BaSO4
19 Pd/BaSO4
20 Pd/C
-
NaOH (1.5)
NaOH (2.0)
-
-
-
-
-
-
-
-
7
<1
33
<1
5
5
0
<1
<1
<1
<1
4
4
0.5
0.5
0.5
4
8
2
2
11
6
3
21 Pd/C
20
20
4
4
4
9
22 Pd/BaSO4
23 Pd/BaSO4
24 Pd/BaSO4
29
13
6
18
22
CeIV (0.03) j
p-MP (0.05) k
4
25
-
-
-
-
24
26
m
26 BaSO4
-
4
6
a
b
c
d
Reaction conditions: citric acid (0.2 mmol), water (2 mL), 2 bar N2. Catalyst-to-substrate ratio. Methylsuccinic acid. Propane-1,2,3-tricarboxylic acid.
e ‘2nd deca’ represents isobutyric acid, butyric acid and methacrylic acid. f ‘Fragmentation’ represents acetone, acetic acid, pyruvic acid and lactic acid.
g ‘Itaconic isomers’ represents itaconic acid, mesaconic acid and citraconic acid. 6 bar N2. Includes 12% of 2-hydroxyisobutyric acid. Ce(SO4)2.
h
i
j
k p-Methoxyphenol. l Includes 10% of β-carboxy- -butyrolactone, as a hydration and ring-closure product of itaconic acid. m 17 mg BaSO4.

2 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C6SC04541C
Scheme 1. Reaction network for the decarboxylation of citric acid in the presence of H2. The detailed identification of the observed (numbered) compounds is given in the ESI.
The beneficial effect of an acidic environment on the
production of methylsuccinic acid (5) can be threefold: (i) the
formation of fragmentation products may be promoted by a
more alkaline medium; ii) the initial dehydration of citric acid
to aconitic acid is acid-catalyzed; iii) the (partly spontaneous)
decarboxylation of aconitic acid requires the uptake of a
proton by the double bond (Scheme 2).
Scheme 2. Heterolytic reaction mechanism of the spontaneous decarboxylation of
aconitic acid to itaconic acid.15,16
Next, various supported Pd catalysts were screened for the
conversion of citric acid (1) to methylsuccinic acid (5) using the
conditions of the reaction in entry 4 (Table 1, entries 4-8). Data
on metal dispersion and texture of the catalysts are given in
Next, the influence of the temperature was studied
(Table 1, entries 15-17). A higher temperature of 250°C results
in more fragmentation products, more further decarboxylation
and therefore in a methylsuccinic acid yield of only 58%. When
the temperature was decreased to 200°C and further to 175°C,
less fragmentation products and less further decarboxylation
were observed. However, at these temperatures the
decarboxylation is slower and hydrogenation competes with
the first decarboxylation, resulting in the formation of
the ESI. The highest yield so far of methylsuccinic acid (5, 81%)
was obtained with Pd supported on ZrO2 and BaSO4 (entries 5,
7). With catalysts containing highly dispersed Pd (e.g. Pd/C,
Pd/Al2O3 or Pd/MgAl2O4; see ESI),19,20 side or consecutive
reactions are occurring somewhat more prominently.
Examples are the further decarboxylation of itaconic acid and
its isomers (2-4) on Pd/C or Pd/Al2O3 (entries 4, 8),13 or the
hydrogenation to propane-1,2,3-tricarboxylic acid (10), even
before the first decarboxylation can occur, as in the reaction
with Pd/MgAl2O4 (entry 6).
The commercial Pd/BaSO4 was further used to optimise the
reaction conditions. First, the effect of an increasing H2
pressure was investigated (Table 1, entries 9-11). An increase
to 8 bar has no impact, which indicates that the formation of
fragmentation products is not in direct competition with the
hydrogenation and thus that these products most probably
propane-1,2,3-tricarboxylic acid
(10). Therefore 225°C is
considered as the optimal temperature. Moreover, from the
time course it is clear that a reaction time of only 40 min
suffices at this temperature
methylsuccinic acid ( ) even reaches an optimum of 86% at
this point (Table 1, entry 19). At 175°C the reaction is markedly
(Figure S1). The yield of
5
slower; only 12% conversion of citric acid (1) is reached after
40 min (Table 1, entry 18).
Summarising, to reach a high yield of methylsuccinic acid
5) the initial dehydration rate must surpass the fragmentation
(
rate (cfr. infra) and the first decarboxylation has to occur faster
than the hydrogenation, which in turn must be quicker than
the subsequent decarboxylation. The first decarboxylation
readily occurs at 225°C and the hydrogenation is fast enough
using 4 mol% Pd/BaSO4 and 4 bar H2. The question arises
whether this hydrogenation can also be rapid enough using
only 0.5 mol% Pd, which is an industrially relevant catalyst-to-
substrate ratio. For a more rapid hydrogenation either a larger
amount of Pd, a higher dispersion of Pd or a higher H2 pressure
is needed. Since the former is now lowered to 0.5 mol% Pd,
compensation by the other two parameters is required.
Considering the much higher dispersion of Pd/C compared to
Pd/BaSO4 (32% vs. 6%) and given that the promoting effect of
Pd/C on further decarboxylation would be suppressed at
higher H2 pressures, the focus turned to Pd/C.20–23 A range of
originate directly from citric acid (1, cfr. infra). Further increase
of the H2 pressure to 12 bar however leads to the production
of propane-1,2,3-tricarboxylic acid (10) and to an increased
production of acetic acid (13), indicating that a higher H2
pressure is not favourable in this case.
Subsequently, the pH of the aqueous reaction mixture was
varied (Table 1, entries 9, 12-14). By adding various amounts
of NaOH (0-2 eq.), the pH of the starting solution was varied
gradually between 2 and 5. A yield of 84% was obtained for
methylsuccinic acid (5) when no NaOH was added. This rapidly
decreased with increasing pH, especially due to the production
of acetic acid (13). Besides, from the addition of 1.5 eq. NaOH
onwards, also lactic acid was produced. This compound
presumably arises from the hydrogenation of pyruvic acid (12).
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H2 pressures was screened using 0.5 mol% Pd/C (Table S3). environment, a carboxylate anion is proposed to lose an
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From 8 bar H2 onwards, the formation of ‘2nd decarboxylation’ electron in the first step. The generated rDaOdIi:c1a0l.1t0h3e9n/Ce6lSimC0in45a4t1eCs
products was minimal, resulting in an optimal yield of 84% CO2, forming another radical that further reacts via a
methylsuccinic acid (5; Table 1, entry 20). For the lower β-cleavage. The β-cleavage in reaction A results in the
dispersed Pd/BaSO4 even a H2 pressure of 20 bar was not formation of pyruvic (12) and acetic acid (13). Pyruvic acid is
enough for an adequate hydrogenation: only 36% not stable and further decarboxylates to acetaldehyde
methylsuccinic acid (
unsaturated products (methacrylic acid, itaconic acid and its form CO and methane, which is lost from solution. The
isomers) left in solution (Table 1, entry 22 vs. 21). presence of methane and CO (traces), was also confirmed by
Finally, to sort out where acetone (11), pyruvic (12) and gas phase Fourier transform infrared spectroscopy. In reaction
acetic acid (13) originate from, first a reactivity study was the β-cleavage forms acetoacetic acid, which further
performed on several intermediate compounds using the decomposes to acetone (11).24 Lastly, the β-cleavage in
optimized conditions of entry 19 (Table 2, entries 1-4). The reaction produces itaconic acid ( ), which further reacts
unsaturated tricarboxylic acid aconitic acid is quickly according to Scheme 1. To corroborate this degradation
5
) was produced and there were still
(
Figure S1).24 This aldehyde is then decarbonylated on Pd to
B
C
2
decarboxylated and hydrogenated to methylsuccinic acid (
5
,
mechanism an isotopic labelling experiment with
entry 1). The relatively large amount of propane-1,2,3-
tricarboxylic acid (10) formed, can be explained by the lower
onset temperature for hydrogenation in comparison to
decarboxylation. In contrast, unsaturated dicarboxylic and
monocarboxylic acids are preferentially hydrogenated to the
corresponding saturated carboxylic acids (entries 2-4). No
fragmentation products were observed starting from these
compounds. Moreover, further examination shows that the
saturated carboxylic acids are rather stable, as shown by the
limited conversion after 6 h (Table 2, entries 5-7). Apparently,
carboxylic acids need to be activated for
a smooth
decarboxylation, like in α,β-unsaturated carboxylic acids. All
this means that the fragmentation products originate directly
from citric acid. To check whether this process has radical-type
intermediates, an attempt was made to both accelerate and
slow down the fragmentation by the addition of a one-electron
acceptor (CeIV) and
a radical trap (p-methoxyphenol),
respectively (Table 1, entries 23-24). The addition of CeIV
increases the amount of fragmentation products from 6% to
15%; this undoubtedly shows that the fragmentation process is
radical in nature. Although the amount of fragmentation
products was not reduced by adding p-methoxyphenol, the
yield of methylsuccinic acid (5) did increase from 86% to 89%.
This indicates that the mass loss from solution partly occurs
through radical intermediates. Based on these observations a
mechanism for the formation of acetone (11), pyruvic (12) and
acetic acid (13) is proposed in Scheme 3. Since this process is
both radical in nature and promoted by a more alkaline
Scheme 3. Radical fragmentation routes for citric acid, explaining the formation of
acetone, acetic acid, pyruvic acid, methane and CO.
Table 2. Reactivity and stability of intermediates and products in the decarboxylation of citric acid. a
Selectivity [%]
t
[h]
Conversion
[%]
Substrate
PTA b
MSA c
BA d
IBA e Fragmentation f
1
2
3
4
5
6
7
Aconitic acid
Mesaconic acid
Itaconic acid
Methacrylic acid
Propane-1,2,3-tricarboxylic acid
Methylsuccinic acid
Isobutyric acid
0.33
0.33
0.33
0.33
6
>99
>99
>99
>99
8
18
-
-
-
-
81
88
86
-
>99
-
<1
1
1
1
2
2
93
<1
25
-
<1
<1
<1
<1
<1
<1
<1
-
<1
<1
-
6
6
12
19
-
-
-
a Reaction conditions: substrate (0.2 mmol), 4 mol% Pd/BaSO4, water (2 mL), 2 bar N2 + 4 bar H2, 225°C. b Propane-1,2,3-tricarboxylic acid. c Methylsuccinic
acid. d Butyric acid. e Isobutyric acid. f ‘Fragmentation’ represents acetone, acetic acid, pyruvic acid and lactic acid.
4 | J. Name., 2012, 00, 1-3
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citric acid-2,4-13C was performed under the ‘blank’ reaction
conditions, without a catalyst (ESI). The distribution of 13C
throughout the different side products is entirely consistent
with the proposed reaction mechanisms.
16 R. T. Arnold, O. C. Elmer and R. M. Dodson, J. Am. Chem.
View Article Online
Soc., 1950, 72, 4359.
DOI: 10.1039/C6SC04541C
17 WO Pat., WO/2004/076398, 2004.
18 S. Wang, Z. Wang, L. Yang, J. Dong, C. Chi, D. Sui, Y. Wang, J.
Ren, M. Hung and Y. Jiang, J. Mol. Catal. A: Chem., 2007, 264,
60.
19 F. De Schouwer, L. Claes, N. Claes, S. Bals, J. Degrève and D.
E. De Vos, Green Chem., 2015, 17, 2263.
20 M. Casagrande, S. Franceschini, M. Lenarda, O. Piccolo and
A. Vaccari, J. Mol. Catal. A: Chem., 2006, 246, 263.
Conclusions
In conclusion, the direct formation of methylsuccinic acid
from citric acid was successfully achieved in water via the new 21 J. Su, M. Lu and H. Lin, Green Chem., 2015, 17, 2769.
22 J. G. Immer and H. H. Lamb, Energy Fuels, 2010, 24, 5291.
23 J. P. Ford, J. G. Immer and H. H. Lamb, Top. Catal., 2012, 55,
175.
24 C. Ferri, Reaktionen der organischen Synthese, Georg Thieme
Verlag, Stuttgart, 1978.
reaction sequence of dehydration, decarboxylation and
hydrogenation. An optimal balance between the different
reaction rates was reached at 225°C for a reaction time of
merely 40 min using 4 mol% Pd/BaSO4 with 4 bar H2 or using
only 0.5 mol% Pd/C with 8 bar H2, leading to a methylsuccinic
acid yield of 86% and 84%, respectively. In addition, the radical
fragmentation of citric acid to acetone, acetic and pyruvic acid
could drastically be reduced by working in a more acidic
environment, i.e. at the natural pH of citric acid.
Acknowledgements
J.V. thanks FWO for
a doctoral fellowship. D.E.D.V.
acknowledges IWT and FWO for research project funding, the
Flemish government for long-term structural funding through
Methusalem and Belspo (IAP-PAI 7/05) for financial support.
The assistance of Karel Duerinckx and Werner Wouters with
1H-NMR and pressure reactors is very much appreciated.
Finally, Free De Schouwer is thanked for our fruitful
discussions.
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