PdPb-Catalyzed decarboxylation of proline to pyrrolidine: Highly selective formation of a biobased amine in water

Article abstract of DOI:10.1021/acscatal.6b02561

Amino acids have huge potential as platform chemicals in the biobased industry. Pd-catalyzed decarboxylation is a very promising route for the valorization of these natural compounds derived from protein waste or fermentation. We report that the highly abundant and nonessential amino acid L-proline is very reactive in the Pd-catalyzed decarboxylation. Full conversions are obtained with Pd/C and different Pd/MeO_x catalysts; this allowed the identification of the different side reactions and the mapping of the reaction network. Due to the high reactivity of pyrrolidine, the selectivity for pyrrolidine was initially low. By carefully modifying Pd/ZrO₂ with Pb in a controlled mannervia two incipient wetness impregnation stepsthe selectivity increased remarkably. Finally, a thorough investigation of the reaction parameters resulted in an increased activity of this modified catalyst and an even further enhanced selectivity under a low H₂ pressure of 4 bar at 235 °C in water. This results in a very selective and sustainable production route for the highly interesting pyrrolidine.

Full text of DOI:10.1021/acscatal.6b02561

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Article
PdPb catalyzed decarboxylation of proline to pyrrolidine:
highly selective formation of a bio-based amine in water
Jasper Verduyckt, Maarten Van Hoof, Free De Schouwer, Marike Wolberg, Mert Kurttepeli,
Pierre Eloy, Eric M. Gaigneaux, Sara Bals, Christine E. A. Kirschhock, and Dirk E. De Vos
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b02561 • Publication Date (Web): 16 Sep 2016
Downloaded from http://pubs.acs.org on September 18, 2016
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PdPb catalyzed decarboxylation of proline to
pyrrolidine: highly selective formation of a bio-
based amine in water
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Jasper Verduyckt,a Maarten Van Hoof,a Free De Schouwer,a Marike Wolberg,a Mert Kurttepeli,b
Pierre Eloy,c1 Eric M. Gaigneaux,c2 Sara Bals,b Christine E. A. Kirschhock,a Dirk E. De Vos*a
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
b Electron Microscopy for Materials Science, UA - University of Antwerp, Groenenborgerlaan
171, 2020 Antwerp, Belgium
c Institute of Condensed Matter and Nanosciences, c1 SUrface Characterization platform and
c2 MOlecules Solids & reactiviTy, UCL – Université catholique de Louvain, Place L. Pasteur 1,
Post Box L4.01.09, 1348 Louvain-la Neuve, Belgium
ABSTRACT. Amino acids have huge potential as platform chemicals in the bio-based industry.
Pd catalyzed decarboxylation is a very promising route for the valorization of these natural
compounds derived from protein waste or fermentation. We report that the highly abundant and
non-essential amino acid L-proline is very reactive in the Pd catalyzed decarboxylation. Full
conversions are obtained with Pd/C and different Pd/MeOx catalysts; this allowed to identify the
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different side reactions and hence to map the reaction network. Due to the high reactivity of
pyrrolidine, the selectivity for pyrrolidine was initially low. By carefully modifying Pd/ZrO2
with Pb in a controlled manner – i.e. via two incipient wetness impregnation steps – the
selectivity increased remarkably. Finally, a thorough investigation of the reaction parameters
resulted in an increased activity of this modified catalyst and an even further enhanced selectivity
under a low H2 pressure of 4 bar at 235°C in water. This results in a very selective and
sustainable production route for the highly interesting pyrrolidine.
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KEYWORDS. PdPb, decarboxylation, L-proline, pyrrolidine, bio-based amine, water
Introduction
Amines are versatile building blocks for the synthesis of organic compounds, such as dyes,
agrochemicals and pharmaceuticals.1 Pyrrolidine is for example used in the synthesis of nicotine
and rifamycin antibiotics.2,3 Currently, this secondary amine is produced via the high temperature
dehydration of 1,4-butanediol in the presence of ammonia using e.g. a ThO2-Al2O3 catalyst at
300°C.1 The diol on its turn is synthesized via oxidation of the fossil-based butane to maleic
anhydride, which is subsequently hydrogenated to 1,4-butanediol in the DAVY process.4 The
different redox transformations render this route to pyrrolidine very inefficient. In this work we
propose an alternative sustainable pathway for the synthesis of this important amine, starting
from the amino acid L-proline as a renewable resource.
Amino acids can be produced in a green way via fermentation.5,6 More importantly however,
they will become increasingly available from protein rich waste streams.7 Common agricultural
waste fractions such as poultry feathers, dried distillers grains with solubles and press cakes from
rapeseed, soybeans, algae, etc. contain up to 90% of proteins.8 Sanders et al. predict that in this
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way more than 100 million tons of protein will be available if 10% of the fossil transportation
fuel is replaced by biomass-derived fuels.9 Work-up of these proteins includes extraction,
hydrolysis and subsequent separation of the amino acids. This final step still remains a big
challenge, though new technologies based on electrodialysis and adsorption are emerging.10–14
Amino acids have huge potential as platform chemicals in the bio-based industry.7 They can be
catalytically converted to valuable nitriles via oxidative decarboxylation,15–18 and to amino
alcohols via hydrogenation.19,20 Another very interesting class of valorization reactions is the
direct decarboxylation to form amines. This reaction is e.g. catalyzed by enzymes or by α,β-
unsaturated ketones that mimic the pyridoxal 5’-phosphate cofactor.10,11,21 The use of enzymes
suffers however from the need for an expensive cofactor in combination with a strict pH control
and from a low volumetric productivity.10,11,22 The use of homogeneous organocatalysts on the
other hand suffers from the mandatory use of an organic solvent in combination with high
catalyst loading and difficult catalyst recycling.21 A viable alternative is the direct Pd catalyzed
decarboxylation, which was first applied to the decarboxylation of fatty acids for the production
of diesel-like compounds at 300°C.23,24 Typically, the reaction is conducted with zerovalent Pd
nanoparticles on a support. Recently, this technology was successfully adapted for the
decarboxylation of itaconic acid to methacrylic acid and of (pyro)glutamic acid to 2-pyrrolidone
in water at 250°C.25,26 The extension of this technology to the production of amines from other
amino acids has so far not been reported, obviously due to the instability of amines under these
reaction conditions.
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In this work the Pd catalyzed decarboxylation is successfully extended to the first highly
selective formation of a bio-based amine in water, using L-proline as the substrate. An essential
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step to obtain high selectivities was the careful modification of the Pd catalyst with Pb via a new,
controlled two-step incipient wetness approach.
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Results & Discussion
Pd catalyst screening and unraveling the complex reaction network
In an initial screening different Pd catalysts were tested for the decarboxylation of L-proline
(1) to pyrrolidine (2) with water as the solvent, using 4 mol% Pd at 6 bar N2 and 225°C for 6 h
(Table 1, entries 1-6). These reaction conditions were inspired by those recently reported by our
group for the decarboxylation of pyroglutamic acid.26 In general, L-proline (1) is very reactive
for the decarboxylation, since almost all catalysts attain full conversion already at 225°C. The
high conversions obtained with different catalysts allowed to identify the side products and
hence to map the reaction network (Scheme 1). Due to its high reactivity, the selectivity to
pyrrolidine (2) was initially low (2-33%). The first side route is the dehydrogenation of
pyrrolidine (2) to form pyrrole (3 - pathway A), which was observed especially for Pd/Al2O3 and
Pd/ZrO2. This reaction is known to be Pd catalyzed; group-IV metal oxide supports, like ZrO2
and TiO2, are known to favor the pyrrolidine dehydrogenation.27 Pathway B leads to a plethora
of side products, starting with a single dehydrogenation to form 1-pyrroline (4), which was
1
identified using H-NMR and GC-MS. This cyclic imine is hydrated to pyrrolidin-2-ol and its
linear counterpart γ-aminobutyraldehyde. The cyclic amino alcohol is then again dehydrogenated
to form 2-pyrrolidone (5). The latter is rather stable, but can be hydrolyzed to a minor extent,
which consecutively opens the route to propionic acid (9).26 The linear amino aldehyde is less
stable and is most probably the origin of more side products, such as butyric acid (10),
γ-hydroxybutyric acid (11) and γ-butyrolactone (12). The most important pathway C is initiated
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by the ring opening hydrogenolysis of pyrrolidine (2).28 H2 can be generated in situ in the water-
gas shift reaction of CO formed in decarbonylation reactions (cfr. infra).26 In this way
n-butylamine (6) is formed, which is subsequently fully defunctionalized to propane (7) and
other volatile compounds. The presence of propane (7) was proven by performing gas phase
Fourier transform infrared spectroscopy (FTIR) on the headspace of the reaction in entry 1
(Table 1). n-Butylamine (6) was merely observed in trace amounts, since it is highly reactive
and readily defunctionalized to propane (7) and other volatiles. This was demonstrated with a
reaction under the same conditions, starting from the linear amine: n-butylamine (6) was
converted for 92% and only traces of products could be found in solution, while CO, CO2, NH3
and propane (7) were detected in the gas phase. The equilibrium between CO and CO2 was
clearly in favor of CO2 (CO/CO2 = 0.04); this confirms the occurrence of the water-gas shift
reaction under these conditions. Finally, if L-proline (1) is not converted quickly enough, it gets
the opportunity to react through a double intermolecular condensation; this gives rise to the
diketopiperazine cyclodi-L-prolyl (8). This reaction represents most of the conversion in the
blank reaction (Table 1, entry 13). The detailed identification of the observed compounds is
given in the supporting information.
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Table 1. Pd catalyst screening for the decarboxylation of L-proline to pyrrolidine.a
Selectivity [%]
Conversion
[%]
Catalyst
Pyrrolidine DKP b Pathway A c Pathway B d Pathway C e
1
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6
Pd/C
>99
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<1
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Pd/Al2O3
Pd/BaSO4
Pd/CaCO3
Pd/MgAl2O4
Pd/ZrO2
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>99
>99
>99
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<1
<1
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PdPb/CaCO3
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PdPb/ZrO2 (A)
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10 Pd/Al2O3
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11 Pd/ZrO2
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12 PdPb/ZrO2 (B)
13 -
<1
a
Reaction conditions: L-proline (0.2 mmol), 4 mol% Pd, water (2 mL), 225°C, 6 bar N2, 6 h.
b Cyclodi-L-prolyl, a diketopiperazine. c Side product from Pathway A is pyrrole. ‘Pathway B’
represents 1-pyrroline, 2-pyrrolidone, propionic acid, butyric acid, γ-hydroxybutyric acid and
γ-butyrolactone. e ‘Pathway C’ represents n-butylamine and mass loss from solution, resulting in
the formation of propane and other volatiles. f 215°C.
d
Scheme 1. Reaction network for the decarboxylation of L-proline. The detailed identification of
the observed (numbered) compounds is given in the supporting information.
Modification with Pb
In search for a more selective catalyst to transform L-proline (1) into pyrrolidine (2), the
modification of Pd with Pb was explored (Table 1, entries 7-9). Besides the commercially
available PdPb/CaCO3, also PdPb supported on a more acidic (ZrO2) and a more basic
(MgAl2O4) support were synthesized. The catalysts were prepared via a one-step impregnation
with (NH3)4PdCl2 together with Pb(NO3)2 according to Furukawa et al.,29 followed by
calcination and reduction. This clearly has a beneficial effect; the selectivity towards pyrrolidine
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(2) typically increases with more than 30%, irrespective of the support. PdPb/ZrO2 (A), the most
selective catalyst so far, already displays a pyrrolidine selectivity of 50% at 44% conversion.
One might think that this increase is just due to a decrease in conversion. However, when
samples were analyzed at lower conversions using the conventional Pd catalysts, the selectivity
never exceeded 25% (Table 1, entries 10-11). The selectivity increase is mainly due to the
suppression of pathway C; ring opening hydrogenolysis of pyrrolidine (2), which opens the route
towards propane (7), seems to be inhibited by the addition of Pb to Pd. Nevertheless, the latter
reaction route is not completely blocked yet. This most likely results from the incomplete
modification of Pd. Therefore the most selective catalyst was synthesized in a new, controlled
manner to carefully modify all Pd sites. In this new method first Pd was distributed onto the ZrO2
support by incipient wetness impregnation; subsequently the material was dried and calcined to
remove the ligands. Afterwards, Pb was evenly deposited onto Pd by a second incipient wetness
impregnation step. After a final drying, calcination and reduction step, PdPb/ZrO2 (B) was
obtained. For this newly synthesized catalyst the selectivity towards pyrrolidine (2) further
increased up to 67% (Table 1, entry 12). Now the ring opening hydrogenolysis of pyrrolidine (2)
is completely blocked, owing to the efficient modification of all Pd sites with Pb. In addition, Pb
also significantly suppresses the dehydrogenation path towards pyrrole (3).
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In order to prove that the higher selectivity of PdPb/ZrO2 (B) compared to PdPb/ZrO2 (A) is
due to the better coverage of Pd with Pb, both catalysts were extensively characterized by high
angle annular dark field – scanning transmission electron microscopy (HAADF-STEM) in
combination with energy dispersive X-ray spectroscopy (EDX), by high resolution powder X-ray
diffractometry (XRD) and by CO chemisorption. The particle size distribution of both samples
was rather narrow with most of the nanoparticles situated between 4 and 8 nm (Figure S1).
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However, the high resolution X-ray diffractogram of the PdPb/ZrO2 (A) sample shows
unambiguous signals of a pure Pd phase (Figure 1). This clearly indicates that not all Pd is
intimately mixed with Pb. Such signals are totally absent in the diffractogram of PdPb/ZrO2 (B).
Pd and Pb were used in the synthesis in a 3-to-1 molar ratio to produce the Pd3Pb alloy that was
proposed by Furukawa et al.29 No evidence for this alloy was found in the XRD data, though this
might be due to the much smaller nanoparticles formed in our synthesis, viz. 4-8 nm vs.
14-20 nm. HAADF-STEM imaging accompanied with EDX analysis was performed in order to
determine the nature of the elements at the catalyst surface. Figure 2 presents HAADF-STEM
images (Figure 2-(a) and -(g)) and EDX elemental maps (Figure 2-(b-e) and -(h-k)) of both the
PdPb/ZrO2 (A) and PdPb/ZrO2 (B) sample. The observed signals from Pd and Pb are visualized
in red and green, respectively. By overlaying the EDX elemental maps of the Pd and Pb it is
clear that for PdPb/ZrO2 (A) the presence of Pd does not always correspond to the presence of Pb
(Figure 2-(f)). However, for PdPb/ZrO2 (B) the presence of Pd predominantly coincides with the
presence of Pb (Figure 2-(l)). These measurements therefore confirm the hypothesis that Pd is
much better covered by Pb in PdPb/ZrO2 (B) than in PdPb/ZrO2 (A). In addition, CO
chemisorption experiments showed a lower apparent Pd dispersion for PdPb/ZrO2 (B) compared
to PdPb/ZrO2 (A): 2.9% vs. 4.7% (Table 2). Since HAADF-STEM revealed very similar Pd
particle size distributions for both catalysts, this difference is attributed to the better coverage of
Pd by Pb in PdPb/ZrO2 (B): when Pb is better covering the Pd surface, less CO is able to adsorb
onto that surface. The same effect was observed in literature for CO chemisorption on Pd
nanoparticles decorated or alloyed with Ga2O3, Sn, K, Mn and Cu.30–32 Finally, X-ray
photoelectron spectroscopy was performed to determine the electronic state of Pd and Pb in
Pd/ZrO2 and PdPb/ZrO2 catalysts (Table S1, Figure S2-3). Pd was always in the metallic state,
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characterized by 3d5/2 emission peaks at 335.5 eV. This value corresponds very well with the
335.4 eV that was previously reported for Pd0/ZrO2.33 Pb was in all catalysts present in both
metallic and cationic states, as determined from 4f7/2 emission peaks at 136.6 and 138.8 eV,
respectively. These values are in accordance with those reported for Pb0 (137.1 eV) and PbO2
(139.1 eV).34 The presence of cationic Pb species might originate from exposure of the catalysts
to air prior to the analysis; or it could mean that Pb was not fully reduced during the catalyst
synthesis. XPS did not give evidence for an influence of Pb on the electronic structure of Pd.
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Figure 1. High resolution diffractograms of PdPb/ZrO2 catalysts. The full pattern of Pd can be
found in the supporting information (Figure S4).
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Figure 2. (a) & (g) HAADF-STEM images and (b-e) & (h-k) EDX elemental maps of
PdPb/ZrO2 (A) (top two rows) and PdPb/ZrO2 (B) (bottom two rows). The overlap of the Pd and
Pb signals can be studied from the mixed EDX elemental maps presented in (f) & (l).
Table 2. Pd dispersion of Pd/ZrO2 and PdPb/ZrO2 catalysts determined via CO chemisorption.
Pd/ZrO2 PdPb/ZrO2 (A) PdPb/ZrO2 (B)
Pd dispersion [%]
8.0
4.7
2.9
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Fine-tuning the reaction conditions
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The modified PdPb/ZrO2 (B) material is so far the best catalyst: it produces pyrrolidine (2)
starting from L-proline (1) with a 67% selectivity, albeit at a rather low conversion of 45%.
Nonetheless, side products from pathway B, as well as the diketopiperazine (8) are still formed.
Further efforts are therefore devoted to increasing the rate of the catalytic reaction and to
blocking the dehydrogenation that initiates pathway B.
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Therefore first a temperature increase was investigated (Table 3). An increasing temperature
leads to an increased conversion; at the optimum of 235°C the selectivity was not affected.
However, at a temperature of 245°C ring opening hydrogenolysis of pyrrolidine (2) became
prominent again, with a re-appearance of pathway C side products.
Table 3. Temperature optimization for the most selective catalyst.a
Selectivity [%]
Temperature Conversion
[°C]
225
235
245
[%]
Pyrrolidine DKP b Pathway A c Pathway B d Pathway C e
1
2
45
67
69
56
11
6
2
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3
20
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<1
<1
14
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3
63
6
a
Reaction conditions: L-proline (0.2 mmol), 4 mol% PdPb/ZrO2 (B), water (2 mL), 6 bar N2,
b
c
6 h.
Cyclodi-L-prolyl, a diketopiperazine.
Side product from Pathway A is pyrrole.
d ‘Pathway B’ represents 1-pyrroline, 2-pyrrolidone, propionic acid and butyric acid.
e ‘Pathway C’ represents mass loss from solution, resulting in the formation of propane and other
volatiles.
Next, the addition of H2 to the reaction atmosphere was explored (Table 4). A low H2 pressure
of 4 bar has a remarkably favorable influence on the activity of the PdPb/ZrO2 (B) catalyst: a
conversion of 88% is now reached within 6 h, with the decarboxylation as the dominant initial
reaction (entries 1-2). In this reducing atmosphere Pd more readily remains in its active
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zerovalent state.35,36 In addition, the selectivity increases to 76%, largely owing to the inhibition
of the secondary dehydrogenation towards pyrrole (3 - pathway A). When the H2 pressure was
increased to 10 bar, again ring opening hydrogenolysis became difficult to impede (entry 3).
Further increase to 15 bar H2 is even detrimental to the conversion level, either because H2
occupies the active sites or because sintering of the metallic nanoparticles occurs (entry 4). For
the reaction at 4 bar H2 the stirring rate was varied (Table S3). This did not result in higher
conversions, indicating that there are no significant mass transfer limitations.
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Table 4. Effect of varying partial pressures of H2 in the reaction atmosphere.a
Selectivity [%]
PH
[bar]
0 f
Conversion
[%]
2
Pyrrolidine DKP b Pathway A c Pathway B d Pathway C e
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2
3
4
52
88
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69
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<1
<1
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<1
15
a Reaction conditions: L-proline (0.2 mmol), 4 mol% PdPb/ZrO2 (B), water (2 mL), 235°C, 2 bar
b
c
N2, 6 h. Cyclodi-L-prolyl, a diketopiperazine. Side product from Pathway A is pyrrole.
d ‘Pathway B’ represents 1-pyrroline, 2-pyrrolidone, propionic acid and butyric acid.
e ‘Pathway C’ represents mass loss from solution, resulting in the formation of propane and other
volatiles. f 6 bar N2.
Finally, Table 5 studies the influence of the pH on the reaction, and especially its effect on
pathway B, which is the only significant side route that subsists for the optimized reaction
(Table 4, entry 2). The pH was adjusted using H3PO4 or NaOH; the natural pH of the starting
solution at room temperature is 7. Both a more acidic and a more alkaline pH decrease the
conversion. The alkaline environment induces a number of unidentified side reactions,
decreasing the selectivity to pyrrolidine (2). On the other hand, the acidic environment results in
a very high selectivity of 91% at 59% conversion, with a nearly total suppression of route B. The
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latter can be interpreted in two ways: i) in acidic conditions the dehydrogenation of pyrrolidine
(2) to 1-pyrroline (4) occurs to a much lesser extent or ii) the decrease in conversion lowers the
probability of consecutive side reactions. To verify which of those is the actual reason, a few
experiments were conducted as a function of time (Table 5, entries 4-5). When the reaction in
the acidic environment was run at longer reaction times to increase the conversion, the selectivity
drastically decreased again due to the formation of pathway B side products. Therefore the first
explanation can be excluded; so the decrease in conversion is responsible for the very high
selectivity. This was confirmed by decreasing the conversion of the reaction at neutral pH by
decreasing the reaction time to 1 h: also in this way a selectivity of 95% was realized at a
conversion of 58% (Table 5, entry 5).
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Table 5. Effect of pH and reaction time.a
Selectivity [%]
Reaction Conversion
pH
2 f
7
time [h]
[%]
59
88
67
97
58
Pyrrolidine DKP b Pathway A c Pathway B d Pathway C e
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2
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a Reaction conditions: L-proline (0.2 mmol), 4 mol% PdPb/ZrO2 (B), water (2 mL), 235°C, 2 bar
b
c
N2 and 4 bar H2. Cyclodi-L-prolyl, a diketopiperazine. Side product from Pathway A is
pyrrole. ‘Pathway B’ represents 1-pyrroline, 2-pyrrolidone, propionic acid, butyric acid,
γ-hydroxybutyric acid and γ-butyrolactone. ‘Pathway C’ represents mass loss from solution,
resulting in the formation of propane and other volatiles. pH was decreased by adding 0.4 eq.
d
e
f
g
h
H3PO4. pH was increased by adding 1 eq. NaOH. Due to the complex product mixture the
mass balance could not be determined accurately.
Mechanistic & kinetic insights
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The new PdPb catalytic system for the decarboxylation of L-proline (1) to pyrrolidine (2) can
now be run at very high selectivities, giving in only a little on the conversion level. The question
remains why this modification with Pb results in a much higher selectivity than observed for the
conventional Pd catalysts. Somorjai and co-workers investigated the formation of pyrrolidine (2)
by the hydrogenation of pyrrole (3) at room temperature on Pt.28 In this case, the ring opening
hydrogenolysis of pyrrolidine (2) to n-butylamine (6) could be avoided by lowering the
desorption energy of pyrrolidine (2). This amine was shown to be surface-bound by the nitrogen
atom. In addition, Furukawa et al. demonstrated that the modification of Pd with Pb renders Pd
more electron rich.29 Consequently, for the present reaction, Pd is expected to interact less
strongly with the nitrogen atom of pyrrolidine (2), facilitating the desorption of the secondary
amine. In this way consecutive side reactions on the Pd surface, such as ring opening
hydrogenolysis can be avoided. In the same way pyrroline can desorb more easily from the Pd
surface, avoiding the further dehydrogenation to pyrrole (3), but also potentially favoring the
hydration to the amino alcohol and the amino aldehyde in pathway B. This switch is possible,
since 1-pyrroline (4) and 2-pyrroline are in tautomeric equilibrium (Scheme 1).
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To substantiate the reaction network that is proposed in Scheme 1, the kinetic profiles of two
reactions were recorded for the decarboxylation of L-proline (1) under the optimized reaction
conditions. Figure 3 depicts the kinetic profile obtained for the highly selective PdPb/ZrO2 (B)
catalyst. At the start of the reaction pyrrolidine (2) is produced very selectively. Pyrrole (3) and
1-pyrroline (4) quickly reach and maintain a low equilibrium concentration. After 1 h pyrrolidine
(2) starts to convert into 2-pyrrolidone (5), which is clearly formed in a consecutive reaction.
This leads to an optimal yield of pyrrolidine (2) of 69% at 86% conversion after 2 h. When the
catalyst was recycled at this point, the conversion dropped due to an initial deactivation;
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however, the conversion in the subsequent runs stabilizes at 50-60% and the selectivity
invariably remains very high, i.e. more than 90% (Table S4). Figure 4 presents the kinetic
profile of the reaction with Pd/ZrO2. L-Proline (1) is decarboxylated very fast, therefore the first
consecutive side reactions are already prominent in the early stages of the reaction. The
formation of pyrrole (3) is initially favored by Pd/ZrO2; this product is however not stable under
the applied reaction conditions. Pyrrole (3) is gradually hydrogenated back to pyrrolidine (2),
which then reacts via one of the other two prominent pathways. The formation of propane (7,
mass loss) therefore steadily increases from the start of the reaction. The concentration of 2-
pyrrolidone (5) increases from the beginning as well, but reaches a plateau due to the subsequent
formation of propionic acid (9).26 Unlike propionic acid (9), butyric acid (10) is formed from the
start of the reaction and is therefore unlikely to originate from 2-pyrrolidone (5). This product is
believed to rather stem from γ-aminobutyraldehyde, which is in equilibrium with pyrrolidin-2-ol
(Scheme 1).
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Figure 3. Time course of the decarboxylation of L-proline using PdPb/ZrO2 (B). Reaction
conditions: L-proline (0.2 mmol), 4 mol% PdPb/ZrO2 (B), water (2 mL), 235°C, 2 bar N2 and
4 bar H2.
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Figure 4. Time course of the decarboxylation of L-proline using Pd/ZrO2. Reaction conditions:
L-proline (0.2 mmol), 4 mol% Pd/ZrO2, water (2 mL), 235°C, 2 bar N2 and 4 bar H2.
Finally, in order to confirm some of the hypotheses on consecutive transformation of the
pyrrolidine product, pyrrolidine itself was reacted for a short time (Table 6). Ring opening
hydrogenolysis, which initiates pathway C, as well as the dehydrogenation to pyrrole (3 -
pathway A) are clearly impaired by the addition of Pb (entries 1, 3, 5). Moreover, the addition of
H2 further decreases the formation of pyrrole (3 - pathway A) (entries 1-2, 5-6).
Table 6. Fate of pyrrolidine under the optimized reaction conditions.a
Selectivity [%]
Catalyst
Pb H2 Conversion [%] Pathway A b Pathway B c Pathway C d
1
2
3
4
5
Pd/BaSO4
Pd/BaSO4
Pd/ZrO2
Pd/ZrO2
PdPb/ZrO2 (B)
PdPb/ZrO2 (B)
-
-
-
-
x
x
-
x
-
x
-
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x
5
a
Reaction conditions: pyrrolidine (0.2 mmol), 4 mol% Pd, water (2 mL), 6 bar N2 or 2 bar N2
b
and 4 bar H2, 235°C, 1 h or 20 min (for Pd/ZrO2). Side product from Pathway A is pyrrole.
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c ‘Pathway B’ represents 1-pyrroline, 2-pyrrolidone, propionic acid and butyric acid.
d ‘Pathway C’ represents n-butylamine and mass loss from solution, resulting in the formation of
propane and other volatiles.
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Conclusion
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The Pd catalyzed decarboxylation has been successfully extended to the highly selective
formation of a bio-based amine in water. During the initial screening of conventional Pd
catalysts for the decarboxylation of the abundant and non-essential L-proline, pyrrolidine turned
out to be very labile. The most important side reactions are initiated by either a dehydrogenation,
leading to pyrrole, 1-pyrroline, 2-pyrrolidone, etc., or by the ring opening hydrogenolysis of
pyrrolidine to n-butylamine, which is further defunctionalized to propane and other volatiles.
This led to very poor selectivities as low as 16% for Pd/Al2O3, the best catalyst reported for the
decarboxylation of (pyro)glutamic acid to 2-pyrrolidone. Modifying the Pd catalysts with Pb was
very favorable for the selectivity to pyrrolidine, owing to the blockage of the ring opening
hydrogenolysis, as well as the partial inhibition of the dehydrogenation to pyrrole. The one-step
impregnation of Pd together with Pb however resulted in an incomplete modification of Pd.
Therefore a new, more controlled synthesis procedure based on a two-step incipient wetness
approach was introduced. This procedure generated a PdPb/ZrO2 catalyst in which Pd is always
intimately mixed with Pb, as evidenced by HAADF-STEM in combination with EDX, by high
resolution XRD and by CO chemisorption. Careful exploration of the reaction parameters finally
resulted in a very active and selective catalyst under a low H2 pressure at 235°C in water. This
new sustainable manufacture of pyrrolidine can be run either for 2 h with a high selectivity
(80%) at high conversion (86%) or for only 1 h with a very high selectivity (95%) at somewhat
lower conversion (58%).
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Experimental section
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Materials
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All chemicals were used as received: L-proline (Sigma-Aldrich, >99%), pyrrolidine (Sigma-
Aldrich, 99%), n-butylamine (Fischer Scientific, laboratory reagent grade), NaOH (Fischer
Scientific, 99.1%), H3PO4 (Chem-Lab, 85% aq. solution), N2 (Air Liquide, α1), H2 (Air Liquide,
N40), O2 (Air Liquide, N25), He (Air Liquide, 99.9997%), CO (Air Liquide, 99.97%), Pd/C
(5 wt%, Engelhard), Pd/BaSO4 (5 wt%, Johnson Matthey), Pd/CaCO3 (5 wt%, Johnson
Matthey), PdPb/CaCO3 (5 wt% Pd, 1 wt% Pb, Johnson Matthey), Al2O3 (Condea Chemie,
Puralox NGa-150), MgAl2O4 (Sigma-Aldrich), ZrO2 (Alfa Aesar), (NH3)4PdCl2.H2O (Sigma-
Aldrich, ≥99.99%), Pb(NO3)2 (Fluka, >98%), benzyl alcohol (Sigma-Aldrich, 99+%) and D2O
(Sigma-Aldrich, 99.9% D).
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Catalyst synthesis
Conventional Pd catalysts (5 wt%) supported on Al2O3, MgAl2O4 and ZrO2 were synthesized
by incipient wetness impregnation according to De Schouwer et al.26 In a typical procedure 1 g
of support was impregnated with a solution of (NH3)4PdCl2 in deionized water. Impregnated
supports were then dried overnight at 60°C, granulated to 250-500 µm particles, followed by
calcination (35 min, 400°C, 2°C/min, 50 mL/min O2) and reduction (1 h, 400°C, 2°C/min,
150 mL/min H2). The synthesized catalysts were stored under N2 until use.
PdPb/ZrO2 (A) and PdPb/MgAl2O4 (5 wt% Pd, 3.27 wt% Pb) were synthesized by
impregnation according to Furukawa et al.29 First (NH3)4PdCl2 and Pb(NO3)2 (Pd:Pb = 3:1 molar
ratio) were dissolved in an aqueous solution (20 mL) by stirring the solution for 2 h at 75°C. 1 g
of support material was then added; afterwards the stirred slurry was completely dried on the
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stirring plate at 75°C. Next, the dried material was granulated to 250-500 µm particles, calcined
(35 min, 400°C, 2°C/min, 50 mL/min O2) and subsequently reduced (1 h, 600°C, 2°C/min,
150 mL/min H2). Finally, the catalysts were stored under N2 until use.
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PdPb/ZrO2 (B) (5 wt% Pd, 3.27 wt% Pb) was synthesized by adapting the incipient wetness
impregnation procedure from De Schouwer et al.26 First, 1 g of ZrO2 was impregnated with an
aqueous solution of (NH3)4PdCl2. After drying and calcining (35 min, 400°C, 2°C/min, air) the
obtained material, it was impregnated with an aqueous solution of Pb(NO3)2 (Pd:Pb = 3:1 molar
ratio). The doubly impregnated support was then dried overnight at 60°C, granulated to
250-500 µm particles, followed by calcination (35 min, 400°C, 2°C/min, 50 mL/min O2) and
reduction (1 h, 600°C, 2°C/min, 150 mL/min H2). Finally, the catalyst was stored under N2 until
use.
Catalyst characterization
XRD patterns were recorded with a Huber Guinier Camera G670 equipped with an image plate
and utilizing Mo-Kα1-radiation. TEM specimens were prepared by crushing the samples in
powder form in an agate mortar and by suspending the resulting powder in ethanol. A drop of
this suspension was deposited on a carbon coated TEM grid. HAADF-STEM images and EDX
elemental maps were collected using an aberration corrected cubed FEI Titan operated at
200 kV, equipped with a Super-X detector for EDX analysis. SEM micrographs were recorded
using a JEOL-6010LV SEM after depositing a Pd/Au layer on the samples using a JEOL JFC-
1300 autofine coater under Ar plasma for 20 s. For CO chemisorption experiments 50 mg of the
catalyst sample was loaded into a tubular reactor, pretreated in a stream of 20 mL/min He at
130°C (heating rate: 10°C/min) for 1 h and subsequently cooled to RT. For the titration of the Pd
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surface, the He flow was reduced to 10 mL/min and pulses of 5 µL 100% CO were given with an
interval of 2 min. The CO concentration in the outlet stream was followed with a Pfeiffer
Omnistar quadrupole mass spectrometer. From the amount of CO adsorbed on the sample, a
dispersion was calculated in the assumption that one CO molecule adsorbs per accessible Pd
atom. N2 physisorption measurements were performed using a Micromeritics 3Flex surface
analyzer at -196°C. Before the measurements, the 100 mg samples were outgassed at 150°C for
6 h under vacuum. The XPS analyses were performed on a SSX 100/206 photoelectron
spectrometer from Surface Science Instruments (USA) equipped with a monochromatized micro
focused Al X-ray source (powered at 20 mA and 10 kV).
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Catalytic reaction
In a typical reaction a solution of L-proline in deionized water (2 mL, 0.1 M) and a catalyst
(4 mol% Pd) were loaded into a stainless steel reactor (11 mL). Next, the reactor was sealed and
the atmosphere was flushed six times with N2. Then, after pressurizing the reactor with 2 bar N2
followed by 4 bar H2, the mixture was magnetically stirred at 500 rpm and heated to 235°C.
After 6 h the reaction was quenched by cooling with water and ice. Afterwards, the catalyst was
separated from the solution by centrifugation. For recycling experiments the separated catalyst
was washed three times with deionized water and dried overnight at 60°C. The catalyst was
reused in a reaction of 2 h using the optimized conditions that are described in this paragraph. In
each run, 5-10% of fresh catalyst was added to make up for the catalyst that was lost during the
recycling.
Product analysis and identification
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To determine the conversion of L-proline and the selectivities to the different products, the
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reaction mixtures were analyzed by H-NMR. Samples were prepared by adding 300 µL of the
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reaction mixture to 300 µL of D2O containing an external standard (benzyl alcohol, 0.1 M).
1H-NMR spectra were recorded on a Bruker Ascend 400 MHz spectrometer equipped with a
BBO 5 mm atma probe and a sample case. The broad signal of water was suppressed by applying
an adapted zgpr pulse program: p1 9.75 μs; plw1 15W; plw9 5.7-05W; o1P on the resonance
signal of water, determined and selected automatically. Besides 1H-NMR, the products were also
identified by gas chromatography coupled to mass spectrometry (GC-MS) with an Agilent 6890
GC, equipped with a HP-5ms column, coupled to a 5973 MSD mass spectrometer. The
identification of gaseous products was done using a Gasmet DX4000 FTIR gas analyzer. The IR
data were processed with Calcmet Standard software version 12.161.
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ASSOCIATED CONTENT
Supporting Information. Particle size distribution of PdPb/ZrO2, XPS data, theoretical
diffraction pattern of Pd, N2 physisorption, mass transfer considerations, recycling experiments
and product identification. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
* E-mail: dirk.devos@kuleuven.be
Author Contributions
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All authors have contributed to the work presented in this manuscript. J.V. and D.E.D.V.
designed the experiments and prepared the manuscript. J.V. and F.D.S. performed catalyst
synthesis. J.V. and M.V.H. carried out the decarboxylation experiments and did the product
analysis. M.W. and C.E.A.K. performed XRD analysis and interpreted the results. M.K. and S.B.
performed HAADF-STEM and EDX analysis and processed the results. P.E. and E.G. performed
XPS analysis and processed the results. All authors have given approval to the final version of
the manuscript.
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Funding Sources
J.V. and F.D.S. thank FWO and IWT for doctoral fellowships. D.D.V. acknowledges IWT and
FWO for research project funding. D.D.V. and C.E.A.K. acknowledge the Flemish government
for long-term structural funding through Methusalem. D.D.V. and S.B. acknowledge Belspo
(IAP-PAI 7/05) for financial support. S.B. is grateful for funding by the European Research
Council (ERC starting grant #335078-COLOURATOMS).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
J.V. and F.D.S. thank FWO and IWT for doctoral fellowships. D.D.V. acknowledges IWT and
FWO for research project funding. D.D.V. and C.E.A.K. acknowledge the Flemish government
for long-term structural funding through Methusalem. D.D.V. and S.B. acknowledge Belspo
(IAP-PAI 7/05) for financial support. S.B. is grateful for funding by the European Research
Council (ERC starting grant #335078-COLOURATOMS). The authors also thank the
Department of Chemistry, University of Cologne, Germany for use of their XRD equipment.
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Finally, the assistance of Karel Duerinckx, Werner Wouters, Walter Vermandel, Ivo Stassen,
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Dries Jonckheere, Sabina Accardo and Bart Bueken with H-NMR, pressure reactors, CO
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chemisorption, N2 physisorption, SEM, gas phase FTIR and high throughput XRD, respectively,
is very much appreciated.
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ABBREVIATIONS
DKP, diketopiperazine.
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