Chemicals from Biomass: Chemoselective Reductive Amination of Ethyl Levulinate with Amines

Article abstract of DOI:10.1021/acscatal.5b01113

N-substituted-5-methyl-2-piyrrolidones have been obtained by reductive amination of ethyl levulinate with amines in the presence of H₂ as reducing agent under solvent-free conditions. The process involves as a first step the formation of an imine intermediate followed by hydrogenation of the imine group and subsequent cyclization into pyrrolidone. Pt/TiO₂ with Pt crystal faces decorated with TiOx is a very active and chemoselective catalyst, being possible to achieve high conversion and selectivity to the corresponding N-substituted-5-methyl-2-pyrrolidones even when other groups susceptible of hydrogenation such as vinyl, carbonyl, or cyano groups are present in the amine moiety. A kinetic study showed that the reaction-controlling step is the formation of the imine intermediate. The rate of formation is enhanced by the presence of protonic acid sites generated on the support by hydrogen dissociation on the metal, resulting in a true bifunctional catalyst for the reaction.

Full text of DOI:10.1021/acscatal.5b01113

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Article
Chemicals from Biomass: Chemoselective
reductive amination of ethyl levulinate with amines
Juan D. Vidal, Maria Jose Climent, Patricia Concepción, Avelino Corma, Sara Iborra, and Maria Jose Sabater
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.5b01113 • Publication Date (Web): 12 Aug 2015
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Chemicals from Biomass: Chemoselective reductive amination of ethyl
levulinate with amines
Juan D. Vidal, Maria J. Climent, Patricia Concepcion, Avelino Corma*, Sara Iborra*,
Maria J. Sabater
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Instituto de Tecnología Química (UPV-CSIC)
Universitat Politécnica de València
Avda dels Tarongers s/n, 46022, Valencia (Spain)
Fax: (+34) 963877809
E-mail: acorma@itq.upv.es
E-mail: siborra@itq.upv.es
Abstract
N-substituted-5-methyl-2-piyrrolidones have been obtained by reductive amination of
2
ethyl levulinate with amines in presence of H as reducing agent under solvent free
conditions. The process involves as a first step the formation of an imine intermediate
followed by hydrogenation of the imine group and subsequent cyclization into
2
pyrrolidone. Pt/TiO with Pt crystal faces decorated with TiOx is a very active and
chemoselective catalyst, being possible to achieve high conversion and selectivity to
the corresponding N-substituted-5-methyl-2-pyrrolidones even when other groups
susceptible of hydrogenation such as vinyl, carbonyl or cyano groups are present in the
amine moiety. A kinetic study showed that the reaction controlling step is the
formation of the imine intermediate. The rate of formation is enhanced by the
presence of protonic acid sites generated on the support by hydrogen dissociation on
the metal resulting in a true bifunctional catalyst for the reaction.
Keywords: Chemicals from biomass, Ethyl levulinate, reductive amination, Pt/TiO
catalyst, N-substituted-5-methylpyrrolidones
2
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Introduction
1
Biomass is recognized as a renewable source of carbon for the production of fuels and
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chemicals
in our way to a more sustainable chemistry. An interesting approach for
converting lignocellulosic biomass into fuels and chemicals is through the
5
transformation of platform molecules that keep sufficient functionality to be
upgraded into valuable compounds. In this context, levulinic acid (4-oxopentanoic acid,
LA) has been identified as a valuable platform molecule which can be easily obtained
,4
from lignocellulose biomass by acidic dehydration of carbohydrates.
2
Many useful
molecules such as gamma-valerolactone (used as liquid fuel, solvent and food
additive), 5-aminolevulinic acid (herbicide and insecticide), levulinic acid esters
(
intermediates), or N-substituted-5-methyl-2-piyrrolidones can be produced from
levulinic acid. Particularly, 5-methyl-2-pyrrolidones are important compounds widely
used in industry as surfactants, intermediates for pharmaceuticals, dispersants in fuel
2
6
,7
additives compositions, solvents, and in the manufacture of agrochemicals etc.
N-substituted-5-methyl-2-piyrrolidones can be produced by reductive amination of
levulínic acid (LA) or its esters with amines, using molecular hydrogen in the presence
of a hydrogenation catalyst. The reductive amination process involves several steps,
starting with the formation of an intermediate imine by the nucleophilic attack of the
amino group to the ketonic group of LA (or ester). Then, the reductive hydrogenation
of imine to amino group has to be performed, followed by the subsequent cyclization
by nucleophilic attack of the amino to the carbonyl group of ester (or acid) to give the
corresponding N-substituted- 5-methyl-2-pyrrolidone (Scheme 1).
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While the reaction appears to be easy, a variety of consecutive and side reactions such
as: reduction or aldolization of the ketoester (or ketoacid), condensation of imines
with amines to give secondary and tertiary amines and over reduction of the aromatic
ring in the case of amines bearing aromatic groups can also occur, which result in a loss
of selectivity. What in practice occurs is that, in general, and depending on the amine
involved, the process suffers from a lack of selectivity and to achieve selectivities
above 90% for near total conversion is a challenge.
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Although the catalytic hydrogenation is an attractive methodology from an economical
and ecological point of view, the number of examples reported in the literature to
transform LA (or its esters) into N-substituted-5-methyl-2-piyrrolidones using
molecular hydrogen in the presence of heterogeneous catalysts is scarce. In gas phase,
the most studied catalysts involve monometallic systems based on Ni supported on
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silica gel, Raney nickel and Pd/Al
2
O
3
. In liquid phase, the reductive amination of LA
,10,11
or its esters with amines has been described in several patents
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using metals such
and
2 3
O . However hydrogen pressures of 55-69 bar and reaction temperatures of 150 -
as Ni, Pd, Pt, Ru, Rh, and Ir supported on carbon or metal oxides such as SiO
Al
80 C, as well as organic solvents such as dioxane were used in all the examples
2
o
1
reported to achieve N-alkyl(aryl or cyclohexyl)- 5-methyl-2-pyrrolidones. Meanwhile,
selectivity, particularly when amines bearing aromatic rings such as for instance aniline
or p-toluidine are involved, ranges between 28 and 65 %. More recently, Touchy et
1
2
x 2 x 2
al. have showed that Pt and MoO co-loaded on TiO (Pt-MoO /TiO ) is an effective
catalyst for the reductive amination of LA with primary amines under solvent-free and
o
mild (100 C, 3bar of H
2
) conditions. The authors showed that the catalyst exhibits high
turnover number and a good substrate scope, achieving yields of N-alkyl-5-methyl-2-
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pyrrolidones between 78-96 %, though long reaction times (20 h) were required.
Moreover, the authors showed that with amines bearing hydrogen-accepting groups
x 2
such as C-C double and triple bonds, the Pt-MoO /TiO catalyst did not show
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chemoselectivity and these groups were completely hydrogenated.
In an interesting work, the reductive amination of levulinic acid has been carried out
using formic acid as a source of hydrogen, on the bases that the formic acid would be
obtained during the transformation of carbohydrates into LA. Then, cyclometalated
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iridium complexes and dichloro(p-cymene)ruthenium (II) dimmer with different
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phosphine ligands (RuCl
2
/PPh
3
complex)
were used to perform the reductive
amination of LA with amines. Nevertheless, the homogeneous catalytic system
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presents the difficulty of catalyst recovery and reuse. More recently, Wei et al. have
reported an efficient catalyst-free transformation of levulinic acid into pyrrolidones
using formic acid and stoichiometric amount of triethylamine in DMSO as solvent.
While the process is interesting, extracting the product from the DMSO became
difficult. Heterogeneous catalysts such as gold nanoparticles deposited on ZrO
ZrO ) have also been reported to promote the transformation of LA and ammonia or
primary amines into 5-methyl-2-pyrrolidones in the presence of formic acid, since Au
on TiO was already successfully used to produce pyrrolidone with ammonia and
2
(Au-
2
2
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amines. Nevertheless the Au-ZrO catalyst described above requires long reaction
times to achieve high yields and its reaction scope is rather limited. For instance, when
o
LA, aniline and formic acid were reacted in water at 130 C, 88% yield of 5-methyl-N-
phenyl-2-pyrrolidone was obtained in 24 hours and no data on catalyst reusability
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were presented.
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In the present work, and given that levulinic acid can be efficiently extracted as alkyl
esters by reactive extraction with different alcohols or with olefins from aqueous
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sulfuric feedstocks, we have studied the synthesis of N-substituted-5-methyl-2-
pyrrolidones by reductive amination of levulinate esters using molecular hydrogen as
reducing agent and have developed highly active and chemoselective of solid catalysts
that are able to work under mild reaction conditions and in absence of solvents. We
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have found that Pt/TiO , with Pt crystal faces decorated with TiOx, is an effective and
chemoselective bifunctional catalyst either in batch or in fixed bed continuous systems
for the reductive amination of ethyl levulinate with primary amines giving the
corresponding N-substituted-5-methyl-2-pyrrolidones in high conversion and
selectivity.
RESULTS AND DISCUSSION
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Noble metals such as Pt, Pd, Rh are largely used as hydrogenation catalyst. When
Au/TiO was used for hydrogenation reactions with hydrogen, their activity was
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generally lower which can be due to the relatively lower activity of gold for hydrogen
activation. This was, in fact, the case for hydrogenation of nitrobenzene and
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substituted nitrobenzenes. In that particular case, the rate of nitrobenzene
hydrogenation on Au/TiO was highly enhanced when 100 ppm of Pt were added to
the catalyst, being the role of the platinum to increase the rate of hydrogen
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dissociation. On the other hand, when gold was fully substituted by Pt, then the rate
of hydrogenation of nitrobenzene derivatives was much higher but the
chemoselectivity was strongly reduced, unless very highly dispersed Pt or Pt decorated
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with TiOx were used.
Taking this into account and the observation that supported
gold was active and selective for the preparation of pyrrolidone by hydrogenation of
succinic and levulinic acid with NH or amines, but under high pressures of hydrogen
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and temperature, we thought on developing an optimized Pt catalyst to perform the
synthesis of N-substituted-5-methyl-2-pyrrolidones at high conversions under mild
reaction conditions. Thus, when the reductive amination of ethyl levulinate (EL) and
o
aniline was carried out on a Pt/TiO
2
catalyst calcined at 450 C, one can deduce from
the shape of the curves (see Figure 1) that the corresponding imine is a primary and
unstable product, while the 5-methyl-N-phenyl-2-pyrrolydone appears as a secondary
and stable product.
From the yields to the products given in Figure 1, it can be deduced that when the
imine is formed, it rapidly reacts to give the aminoester and the final 5-methyl-N-
phenyl-2-pyrrolidone (see Scheme 1). In fact, the cyclization of the aminoester to give
the pyrrolidone (step 3 in Scheme 1) is so fast that the former intermediate product is
not detected. From the above results it appears that the controlling step for the global
reaction can be the formation of imine. To validate that hypothesis, the two steps of
the reaction, i.e., imine formation and imine hydrogenation were studied separately.
Firstly, the reaction between ethyl levulinate and the amine (aniline) was performed in
o
the presence of Pt/TiO
2
calcined at 450 C in the presence of H
2
, but the reaction was
carried out in the presence of nitrogen instead of hydrogen to avoid the subsequent
hydrogenation of the imine (Figure 2). In this case the initial reaction rate (step 1,
-1
Scheme 1) is 0.09 mmolh . On the other hand, when the imine formed in step 1 was
o
independently hydrogenated with Pt/TiO
2
catalyst calcined at 450 C in H
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, the rate of
-1
the reaction was 0. 59 mmolh (Figure 3). These results allow to conclude that, indeed,
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the controlling step in the multistep process given in Scheme 1, is the first one, i.e., the
formation of the imine. However, if the results are further analyzed, it could be
expected that the reaction rate for the global process should be the same than the
-1
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rate of the slowest step i.e., 0.09 mmolh that corresponds to the formation of the
imine. In spite of that, the global rate of the reaction calculated from Figure 1, was
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.39 mmolh . This is clearly larger than the 0.09 mmolh obtained for the formation of
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the imine in nitrogen atmosphere and lower than the 0.59 mmolh for hydrogenation
of the imine. To find one answers to this puzzling situation we considered that: a) the
first step, i.e. imine formation is a reaction that does not require the presence of a
catalyst to occur but, nevertheless the rate can be enhanced in the presence of an acid
catalyst and b) the reaction for independently studying the imine formation, and which
-1
resulted in an initial reaction rate of 0.09 mmolh was not performed exactly under
the same conditions than the global reaction. Indeed, the global reaction was
performed under hydrogen, while when the first step was studied separately, it was
carried out under nitrogen, to avoid subsequent hydrogenation.
From the first consideration, i.e. possible acid catalysis for imine formation, we can
not expect that TiO to behave like a strong solid acid catalyst for this reaction and,
2
indeed, the rate of formation of the imine under N
2
in the presence or absence of the
is
Pt/TiO was 0.09 and 0.004 mmolh-1 respectively indicating that the acidity of TiO
2
2
still limited. However, it is clear from the kinetic results that when the reaction was
carried out in the presence of hydrogen the rate of the imine formation was strongly
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2
increased. A positive effect of H was observed by Santoro et al. who indicate that it
may drag the reaction by withdrawing the imine by hydrogenation. While this could be
2
a possible explanation, an increase in the acidity of the Pt/TiO catalyst in the presence
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of hydrogen, could also contribute increasing the rate of imine formation. In fact, the
formation of protonic acid sites from hydrogen dissociation on metal supported
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catalyst has precedents. Hattori and Shishido showed that hydrogen can be
dissociatively adsorbed on metallic sites (Pt) to form hydrogen atoms which migrate by
spillover to Lewis acid sites of the support. There hydrogen atoms can release one
electron to became a proton that may be stabilized on the oxygen atom near to the
Lewis acid centre of the support generating protonic acid sites that can be active for
acid catalyzed reactions. This can certainly occur in our case considering the
semiconductor characteristics of the support. In fact, IR spectra clearly show the
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formation of new acid sites on the Pt/TiO
S1).
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catalyst in the presence of H (see Figure
Then, confirming our above explanation two additional experiments were carried out.
In a first series of experiments the reductive amination of EL with aniline was carried
out in the presence of TiO2 with no Pt and hydrogen, and only 10% of imine was
detected after 12 hours of reaction time. In a second set of experiments a reaction
typically catalyzed by acid sites such as the acetalization of carbonyl compounds, i.e.
o
cyclohexanone with ethanol, was carried out at 120 C using Pt/TiO as catalysts in the
2
presence and in absence of hydrogen. In absence of hydrogen, we did not observe the
formation of the diethyl acetal of cyclohexanone. However, in the presence of
hydrogen 70% of diethylacetal together with 30% of cyclohexanol was formed after 12
hours, indicating that the acid catalyzed reaction only occurs on Pt/TiO
hydrogen was present.
2
when
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The results given above support the hypothesis that protonic acid sites can be formed
on the surface of Pt/TiO by hydrogen dissociation on Pt and spillover, and the acid
2
sites formed can catalyze the formation of imine. In other words, in this case we have a
bifunctional catalyst.
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Nature of the Pt sites for chemoselective reductive amination
2
After finding that Pt/TiO was an active catalyst for the conversion of EL and aniline
into N-phenyl-5-methyl-2-pyrrolidone, and in our search for a chemoselective catalyst
to prepare N-substituted-5-methyl-2-pyrrolidones, the reductive amination was
performed with a vinyl aniline and EL. Results in Table 1 (entries 2 and 3) show that
when the reductive amination of EL with p-vinylaniline was performed on a Pt/TiO
2
o
catalyst calcined at 250 C in the presence of H (0.2%Pt/TiO2ND) or with 0.2%Pt/TZrO2
2
the chemoselectivity was relatively lower, being the vinyl group also hydrogenated
resulting in the formation of the N-(4-ethylphenyl)-5-methyl-2-pyrrolidone (See
Scheme 2). This result would be in line with our previous observation that Pt/TiO was
2
not a chemoselective catalyst for hydrogenation of substituted nitrobenzenes unless
o
the surface of the Pt was decorated with TiO
2
by calcining the Pt/TiO
2
at 450 C in the
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o
presence of hydrogen. Following that, the Pt/TiO2 was calcined at 450
C
(
0.2%Pt/TiO2D) and the results given in Table 1 clearly show that the resultant catalyst
is not only more active but it is more chemoselective when the reductive amination
was performed with p-vinylaniline (see Table 1, entry 1). As could be expected,
preferential hydrogenation of the imine intermediate also occurred when the aromatic
ring substituents included a carbonyl group or a nitrile group. Since the intrinsic rate
for imine hydrogenation is higher than the rate for hydrogenation of the vinyl group in
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the decorated catalyst, while the opposite occurs in the non decorated catalyst, we
could assume, in first approximation, that there is a preferential adsorption of the
imine versus the double bond on the catalytic site which is responsible for the high
activity and selectivity exhibited by 0.2%Pt/TiO2D catalyst. To test this hypothesis a set
of catalytic experiments combined with an “in situ” IR spectroscopy study were
designed. As reactants model the imine of the ethyl levulinate with butyl amine (ethyl
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-(butylimino)pentanoate) and styrene first separately and then as a mixture were
hydrogenated in the presence of 0.2%Pt/TiO and 0.2%Pt/TiO2ND. The results of TOFs
2
D
for each case are presented in Table 2. As can be observed there the hydrogenation of
the C=C of styrene is highly favored on the 0.2%Pt/TiO2ND compared with 0.2%Pt/TiO2D
while the rate of hydrogenation of the imine (TOF) is superior on 0.2%Pt/TiO than on
,
2
D
0.2%Pt/TiO2ND. Moreover the TOF for imine hydrogenation is practically maintained for
each catalyst when the imine is hydrogenated alone or in the presence of styrene.
However, the hydrogenation of styrene is strongly inhibited when the imine is present
on 0.2%Pt/TiO2ND, and particularly, on 0.2%Pt/TiO2D. These results suggest that
hydrogenation of C=C group does not compete with the hydrogenation of the imine
group on the Pt sites in 0.2%Pt/TiO , due to a possible preferential adsorption of the
2D
imine with respect to the vinyl group.
To further check that hypothesis, the competitive adsorption of the imine formed from
EL and butylamine, and styrene was followed by “in situ” IR spectroscopy. Thus, an
equimolar mixture of imine and styrene adsorbed on 0.2%Pt/TiO2D catalyst (Figure 4)
-1
gave IR bands at 1600 and 1580 cm associated to the ν(C=N) stretching frequency of
-1
the imine, and the IR band at 1660 cm that can be associated to the C=C stretching
frequency in styrene. In other words, both the imine and styrene can adsorb but the
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intensity of the band at 1660 cm associated to styrene is much lower than the
o
o
intensity of the bands associated to the imine at either 25 C or 120 C (Figure 4,
o
spectra b and c respectively). Furthermore, at 120 C when H
2
was introduced (Figure
-1
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4, spectra d) the IR bands associated to the imine, i.e. 1600, 1580, 1466 and 1380 cm
-1
decrease, while the IR band at 1660 cm associated to the C=C group in the styrene
remains practically the same. These results would confirm that the preferential
adsorption of the imine group on the active Pt sites versus the C=C bond, can explain
the high chemoselectivity observed on the 0.2%Pt/TiO sample.
2
D
Effect of crystal size of metal on the catalytic activity
Since the controlling step is the imine formation and, as was discussed above,
hydrogen dissociation and spillover is required to form the Bronsted acid sites on the
support, metal dispersion should have an impact on the rate of reaction. Thus, we
have modified the metal crystallite size by changing the amount of Pt on the support.
Transmission Electron Microscopy (TEM) technique was applied to determine the
particle size distribution of the platinum nanoparticles. The images revealed that the
sizes of the platinum nanoparticles increased by increasing the percentage of platinum
from 0.2 to 5%. The particle distributions presented in Figure 5 were achieved by
treatment of the images using Image software. As observed in the histograms, the
average size of metal nanoparticles and the distribution range increases when
increasing the percentage of platinum on the support. Moreover the IR spectrum of
adsorbed CO (Figure 6) on samples with larger Pt crystal size (5%Pt/TiO2D, 1%Pt/TiO2D
)
-1
showed mainly bands in the 2100-2086 cm region which correspond to CO molecules
adsorbed on Pt (111) terraces (sites with coordination number 9). The IR bands in the
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2077-2071 cm are related to CO molecules adsorbed on Pt(100) sites (Pt sites with
coordination number of 8), which are clearly observed when the crystal size is
decreased from 6-7nm to 4-5nm (1%Pt/TiO2D sample). Finally, IR bands at lower
-
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frequencies (2059, and 2040-2020 cm ) are associated to the presence of Pt sites of
25
low surface coordination, like steps and corners , mainly present on the sample of the
lowest crystal size (0.2%Pt/TiO2D).
When these samples were tested in the reductive amination of EL with aniline it
was observed that the 0.2%Pt/TiO2D sample, with smaller particle size, (i.e higher
proportion of Pt sites within low surface coordination) give the highest activity and
selectivity to 5-methyl-N-phenyl-2-pyrrolidone (see Table 3), indicating that a high
proportion of the imine adsorption sites occur at defects of Pt nanoparticles, which
have to increase when decreasing the crystal size. In fact IR spectra of imine
adsorption on Pt/TiO
2
samples of different sizes shows a stronger interaction on the
sample of lowest crystal size (0.2%Pt/TiO ) versus the sample of bigger crystal size
2
D
(
5%Pt/TiO2D) (Fig.S2a), while an opposite trend is observed when styrene has been
adsorbed on the same samples. In this case a higher interaction is observed on the
sample of biggest crystal size (5%Pt/TiO ) while a lower interaction is observed on the
2
D
smallest one (0.2%Pt/TiO2D) (fig. S2b). These results suggest that the presence of
higher proportion of Pt sites with low surface coordination in the small crystal size
samples (0.2%Pt/TiO2D) are expected to be the chemoselective active sites for
hydrogenation of the imine versus hydrogenation of the C=C bond. In fact, the
reductive amination of etyl levulinate with p-vinylaniline (Table S1), showed 94%
selectivity to the respective pyrrolidone on the small crystal size sample while 95%
selectivity to C=C bond hydrogenation was observed on the bigger crystal size sample.
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Moreover, the Pt-TiO
2
interphase and therefore a higher hydrogen spillover and
potential formation of a higher acidity, can occur for the sample with a higher Pt
dispersion. To check that, the acetalization of cyclohexanone with ethanol was carried
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out in hydrogen on the Pt/TiO
with different Pt dispersion after being treated at 450
2
o
C in hydrogen. The results in Table 4 show an increase in activity (TOF) when metal
dispersion increases.
Scope of the reductive amination
The scope of the reaction was studied by performing the reductive amination of ethyl
levulinate with different aryl, alkyl and cycloalkyl amines with 0.2%Pt/TiO2D as catalyst
and 2000 substrate/catalyst molar ratio. In Table 5 can be seen that aromatic amines
with electron withdrawing groups (entries 11-13), are more reactive than aromatic
amines with electron donating substituents (entries 4-10) which required longer
reaction times in order to reach good yields (92-98%). Moreover, when a substituent
at the 2 position of aniline is present, a strong decrease in selectivity to 5-methyl-2-
pyrrolidone is observed. In these cases, the fact that EL conversion was very high,
while the yield of pyrrolidones was low, could be due to steric hindrance for the
adsorption of the imine intermediate and subsequent hydrogenation (Table 5, entries
4
-6,). In fact, the imine intermediate was the main product detected in the reaction
media, while no other byproducts were detected. In general, good conversions and
selectivities were achieved in the case of alkyl amines and hydroxyamines (entries 17-
2
1) while in the case of cycloalkyl amines the conversion and selectivity strongly
depends on the size of the cycloalkyl ring. This result can be related with the existence
of steric hindrance for the imine formation and subsequent hydrogenation.
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For comparison purposes in Table 5 (entries 3, 9 and 24) we have included the results
10
reported in patent literature when using 5% Pt/C as catalyst. It can be observed that
using a clear excess of hydrogen a limited selectivity, particularly for the formation of
5-methyl-N-aryl-2-pyrrolidones can be achieved which is due to overhydrogenation of
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the aromatic ring. Then, as far as we know, the results presented in this work on the
reductive amination of ethyl levulinate using molecular hydrogen and Pt/TiO2D under
mild reaction conditions, are the best reported up now.
Stability and Reusability of the 0.2%Pt/TiO catalyst
2D
To demonstrate that the catalytic process involves a heterogeneous metallic Pt
species, an additional experiment was carried out where the reductive amination of EL
with octylamine in the presence of 0.2%Pt/TiO2D was stopped after 60 min. At this
point, the catalyst was filtered off and the reaction was continued for an additional 6h,
but no further conversion was detected (Figure 7), indicating that the catalyst is stable
and that active Pt species are not leached into the reaction media which is in good
agreement with the results of ICP analysis.
In order to test the reusability of the catalyst, after being used in the reaction the
catalyst was removed by filtering and washed thoroughly with methanol before each
consecutive reuse (see experimental section). As can be observed in Figure 8, the
conversion and selectivity slightly decrease when the catalyst was subjected to five
consecutive cycles. Thus, a decrease <16% of conversion and <6% in selectivity was
observed after five cycles, being the accumulate TON (mol of pyrrolidone formed/mol
-1
Pt) of 8540 molmol . The slight decrease in activity cannot be attributed to Pt leaching
during the recycle process since the total amount of platinum (0.2%) was maintained
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at least during the five consecutive cycles as detected by ICP-AES. The observed effect
could be attributed to adsorption of organic compounds on the surface of the catalyst.
o
Indeed when the catalyst was calcined at 450 C the catalytic activity was restored.
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Synthesis of pyrrolidones in a fixed bed continuous-flow reactor
After the study of the one pot selective reductive amination of biomass derived ethyl
levulinate with primary amines to obtain pyrrolidones in a batch reactor, we thought
to explore the possibility to carry out the process in a fixed-bed continuous reactor
which may offer industrial advantages when processing larger volumes.
We started our study using Pt/TiO2D as catalyst with different platinum content (0.2%,
1
% and 5%) in the reductive amination of EL with aniline, and the results are displayed
in Figure 9. As expected higher selectivity to 5-methyl-N-phenyl-2-pyrrolidone were
achieved using 0.2%Pt/TiO2D after 4.5h time on stream. Thus, the study of the
influence of different parameters such as, temperature, hydrogen pressure and
contact time (τ) in the fixed bed reactor on the catalytic activity was optimized using
0
.2%Pt/TiO2D as catalyst. For instance in Figure 10 is presented the study of the
influence of the contact time (τ) on the yield of 5-methyl-N-phenyl-2-pyrrolidone.
o
Under optimized reaction parameters, i.e. 150 C, 5 bar of hydrogen, and contact time
(
τ)= 4.5h a ethyl levulinate conversion and 5-methyl-N-phenyl-2-pyrrolidone selectivity
of 85 and 90 % respectively that remain constant during 10 hours on stream were
obtained (see Figure 10).
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Conclusions
It has been successfully performed the reductive amination of ethyl levulinate with
amines yielding the corresponding N-substituted-5-methyl-2-pyrrolidones using H as
reducing agent in the presence of Pt/TiO as catalyst under solvent free conditions. The
2
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process involves as a first step the formation of an imine intermediate followed by
hydrogenation of the imine group and subsequent cyclization into pyrrolidone. The
2
Pt/TiO increases their catalytic activity and chemoselectivity when the Pt crystal faces
are decorated with TiOx, being possible to achieve high conversion and selectivity to
the corresponding N-substituted-5-methyl-2-pyrrolidones even when other groups
susceptible of hydrogenation are present in the amine moiety. A series of reactivity
studies showed that the reaction controlling step is the formation of the imine
intermediate, and the rate of formation is increased by the presence of protonic acid
2
sites generated by spillover on the TiO support of hydrogen dissociated on the metal.
The study of the influence of the metal crystal size on the catalytic activity and
selectivity showed that the sample with the lowest crystal size presents the highest
activity and selectivity to 2-pyrrolidone which was attributed to the presence of their
higher concentration of Pt sites of low surface coordination which are responsible of
the preferential adsorption of the imine intermediate. The optimized catalyst can be
regenerated and reused up to five consecutive cycles showing a slight loss of activity.
However the initial activity could be completely restored after calcinations of the
o
catalyst at 450 C. The Pt/TiO2D can be used to produce a variety of 2-pyrrolidones with
excellent yields. Finally, it is presented that the preparation of N-substituted-5-methyl-
2
-pyrrolidones starting from ethyl levulinate and amines, can be carried out succesfully
in a continuous fixed bed reactor.
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Experimental
Catalysts preparation
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Pt/TiO
the method reported in Ref. Typically, 0.2%Pt/TiO2D catalyst was prepared by a
modified deposition-precipitation (DP) method by mixing TiO powders (5 g) with an
2 2 6
catalysts were prepared by using H PtCl hexahydrate as Pt source according to
2
6
2
appropriate amount of an aqueous solution of hexachloroplatinic acid. The mixture
was stirred over-night at room temperature under inert atmosphere, and then the
o
catalyst was dried at 100 C in a forced air oven for 5 h, followed by reduction with a
o
stream of H
2
at 450 C for 3 h. 0.2%Pt/TiO2ND sample was reduced with a stream of H
2
o
at 250 C for 3 h. The concentration of platinum was 0.2% Pt by weight (ICP-AES
analysis).
2
Pt/ZrO catalyst were prepared by a modified deposition-precipitation (DP) method by
mixing ZrO powders (5 g) with appropriate amounts of aqueous solutions of
2
tetrachloroplatinic acid (10 mL). After overnight stirring at room temperature under
o
inert atmosphere, the catalyst was dried at 100 C in a forced air oven for 5 h, followed
o
by reduction with a stream of H2 at 450 C for 3 h. The concentration of platinum
(
0.2%) was measured by ICP-AES analysis.
Catalysts characterization:
Transmission electron microscopy (TEM) images for supported platinum catalysts
were taken with a JEOL 2100 electron microscope operating at 200 kV. Before being
transferred into the TEM chamber, the samples dispersed with dichloromethane were
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deposited onto a carbon-coated copper grid and then quickly moved into the vacuum
evaporator. The size distribution of the metal nanoclusters was determined by
measuring about 200 random particles on the images.
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Additionally, to reveal subtle details of the surface composition of the Pt
nanoparticles in the catalysts, nanoanalysis by STEM-EELS have been performed.
The Pt loading of the catalysts was measured by inductively coupled plasma atomic
emission spectroscopy (ICP-AES) using a Varian 715-ES spectrometer.
The Infrared spectra (IR) were measured with a Bruker “Vertex 70”
-1
spectrophotometer, at 4 cm resolution and using a DTGS detector. An IR cell allowing
o
o
in situ treatments in controlled atmospheres and temperatures from -176 C to 500 C
has been used and connected to a vacuum system with gas dosing facility.The samples
2
were pressed into self-supporting pellets of 10 mg/cm and activated in situ in the IR
o
cell. For activation the samples were heated at 250 C for 2 h in an hydrogen flow
-6
(15ml/min), followed by 1 h outgassing at the same temperature under 10 mbar
dynamic vacuum conditions. For the IR experiments of CO adsorption, the catalysts,
o
after activation, were cooled down to -176 C under dynamic vacuum conditions
followed by CO dosing at increasing pressure (0.1-1.5 mbar). IR spectra were recorded
after each dosage. For the mechanistic IR studies, the catalysts, after activation, were
o
cooled down to 25 C under dynamic vacuum conditions. 3 mbar of ehtyl4-
(
butylimino)pentanoate were co-adsorbed with 3 mbar of styrene. IR spectra were
recorded in the presence of both reactants after 30 min, collecting spectra at 25ºC and
o
after increasing temperature to 120 C. At that temperature 15 mbar H
2
were added,
and the IR spectra recorded after 30 min reaction time. Preliminar IR experiment in
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which the order of addition of both reactants into the IR cell has been inverted shows
no influence on the final IR sepctrum. Origin software was used for spectra
decovolution.
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General procedure for the production of pyrrolidones by reductive amination of
levulinic acid derivates with amines
2
Catalytic experiments were performed under H atmosphere in a 2mL glass-made
reactor. For each reaction, a mixture of EL (2 mmol), primary amine (2 mmol),
supported metal catalysts (metal 0.05 mol%), and dodecane (0.2 mmol) as internal
standard, were charged into the reactor. After sealing the reactor, air was purged by
flushing twice with 10 bars of hydrogen. Then, the mixture of substrates and catalyst
were heated to the desired temperature in less than 2 minutes and it was pressurized
2
with H at the selected set point.
During the experiment, the pressure was maintained constant and the stirring rate
was fixed at 1000 rpm. Aliquots ( 20 μL) were taken from the reactor at different
~
reaction times. The product composition was analyzed on Agilent GC-7980A gas
chromatograph equipped with a capillary column HP-5 (30m × 0.25µm × 0.25mm) and
FID detector. The identification of the products was performed by using a GC-MS
spectrometer.
Recovery and reuse of Pt/TiO2D
First, 100 mg fresh 0.2%Pt/TiO2D catalyst was used in a mixture containing EL
(
2mmol), amine (2mmol) in 2 mL pressure reactor. The reaction was performed
according to previous section. After reaction, the catalyst was recovered, filtered,
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washed three times with methanol and dried under vacuum at room temperature and
reused in a consecutive run.
Reductive amination reaction in a continuous fixed-bed reactor
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The reductive amination reaction of EL and aniline with 0.2%Pt/TiO2D in a
continuous fixed-bed reactor was performed under hydrogen pressure in a tubular
stainless-steel reactor (400 mm long, 4.25 mm inner diameter). In a typical
experiment, Pt/TiO2D (1.5 g) was pelletized and sieved to a particle size of 0.20–0.40
mm, diluted with silicon carbide and placed in the fixed bed reactor. After that, an
equimolar mixture of EL and aniline was fed by using a syringe pump perfusion at a
rate of 0.5 mLh-1 (which corresponds to a weight hourly space velocity (WHSV) of
0
.223 h-1 or a contact time of 4.50 h) along with a hydrogen flow of 10 mLmin-1 at 5
bar pressure. The reaction temperature, measured by using a thermocouple in direct
contact with the catalytic bed, was maintained during the reaction at the selected
point. The reaction products were analyzed by gas chromatography (GC) and GC–MS
using dodecane as an external standard.
Supporting Information Available
Additional materials available online. This material is available free of charge via the
Internet at http://pubs.acs.org
Acknowledgements
Financial support by Consolider-Ingenio 2010 (project MULTICAT), Spanish MICINN
Project CTQ-2011-27550), Generalitat Valenciana (Prometeo program) and Program
Severo Ochoa are gratefully acknowledged. J.D.V. is grateful to Spanish MICINN for a
doctoral grant.
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References
(1) (a) Corma, A.; Huber, G.W.; Iborra, S. Chem. Rev. 2006, 106, 4044-4098. (b) Vispute,
T. P.; Zhang, H.; Sanna, A.; Xiao, R.; Huber, G.W. Science 2010, 330, 1222-1227. (c)
Climent, M.J.; Corma, A.; Iborra, S. Green Chem. 2014, 16, 516-547.
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2) Corma, A.; Iborra, S.; Velty, A. Chem.Rev. 2007, 107, 2411-2502.
(3) Climent, M.J.; Corma, A.; Iborra, S. Green Chem. 2011, 13, 3, 520-540.
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4) Gallezot, P. Chem. Soc. Rev. 2012, 41, 1538-1558.
5) (a) Werpy, T.; Petersen, G.R. Top Value Added Chemicals from Biomass. Volume I.
Results of Screening for Potential Candidates from Sugars and Synthesis Gas, U.S.D.
Energy, 2004. (b) Bozell, J.J.; Petersen, G.R. Green Chem. 2010, 12, 539-554.
(6) Manzer, L.E. US 6743819 B1, 2004.
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7) Manzer, L.E. US 247443 A1, 2006.
8) (a) Shilling, W.L. US Patent 32355562, 1966. (b) Croock, L.R.; Jansen, B.A.; Spencer,
K.E.; Watson, D.H. GB Patent 1036694, 1996.
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560760, 1985.
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10) Manzer, L.E. US 7129362, 2006.
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(12) Touchy, A.S.; Siddiki, S.M.A.H.; Kon, K.; Shimizu, K. ACS Catal. 2014, 4, 3045-3050.
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410.
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17) Du, X-L.; He, L.; Zhao, S.; Liu, Y-M.; Cao, Y.; He, H-Y.; Fan, K-N. Angew. Chem. Int.
Ed. 2011, 50, 7815-7819.
18) (a) Gurbuz, E. I.; Alonso, D. M.; Bond, J. Q.; Dumesic, J. A. ChemSusChem 2011, 4,
57-361. (b) Peng, L.; Lin, L.; Li, H.; Yang, Q. Appl. Energy 2011, 88, 4590-4596. (c)
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Ayoub, P.M.; Lange, J.P. WO 2008/142127, 2008. (d) Fagan, P.J.; Manzer, L.O. US
US7153996 2006.
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19) a) Bond, G. C. Chemistry & Industry 1967, 2018-2025; b) Kacer, P.; Cerveny, L.
Appl. Catal., A: General 2002, 229, 193-216.
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21) Corma, A.; Serna, P.; Calvino, J.J. J. Am. Chem. Soc. 2008, 130, 8748-8753.
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Scheme 1. Reaction pathway in pyrrolidone synthesis.
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Scheme 2. Reductive amination of EL with 4-vinylaniline in the presence of 0.2%Pt/TiO2ND
.
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Table 1. Reductive amination of EL with different amines bearing reducible groups.
a
b
b
Entry
Catalyst
Amines
t (h)
2
Conv.%
90
Select.%
94
Yield.%
85
1
0.2Pt/TiO2D
c
2
3
4
5
0.2Pt/TiO2ND
2
2
2
2
46
56
91
90
60
28
21
82
81
d
0.2Pt/ZrO
2
37
0.2Pt/TiO2D
0.2Pt/TiO2D
90
90
Reaction conditions: ethyl levulinate (2 mmol), amine (2 mmol), hydrogen (P=10 bar) 100 mg
o
a
b
c
catalyst (0.05 mol%), at 120 C, 2h. EL conversion; selectivity and yield of pyrrolidone; 10%
d
of the pyrrolidone hydrogenated at C=C was detected. 26% of the pyrrolidone hydrogenated
at C=C was detected
.
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Table 2. Results of TOF for the hydrogenation of styrene, ethyl 4-(butylimino)pentanoate, and
a mixture of them using 0.2%Pt/TiO2D and 0.2%Pt/TiO2ND catalyst.
-
1 a
TOF (h )
Imine + styrene mixture
Styrene
Imine
Styrene
Imine
hydrogenation
hydrogenation
hydrogenation
hydrogenation
0
.2wt%Pt/TiO2D
357
632
0
578
174
0.2wt%Pt/TiO2ND
5265
187
19
Reaction conditions: imine (1 mmol), styrene (1 mmol), hydrogen (P = 10 bar) 50 mg catalyst
o
a
-1
(
0.05 mol%), at 120 C. Calculated as mol of product/mol Pt xh
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Table 3. Catalytic activity of different Pt/TiO with different Pt loading in the reductive
amination of EL with aniline.
-
1 a
Pt content (wt%)
Conv. (%)
Yield (%)
TOF (h )
5
1
14
42
98
9
194
29
97
295
0
.2
733
Reaction conditions: EL (2mmol) and aniline (2mmol),
o
catalysts (0.05 mol%), hydrogen (10 bar), 6h, at 120 C.
a
-1
Calculated as mol of product/mol Pt xh
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Table 4. Initial reaction rates of acetalization of cyclohexanone with ethanol using Pt/TiO
2
samples with different metal dispersion.
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1 a
-1 b
TOF (h )
Catalyst
r
0
(mmol h )
0
.2wt%Pt/TiO2D
0.35
682
390
292
1wt%Pt/TiO2D
wt%Pt/TiO2D
0.20
5
0.15
Reaction conditions: Cyclohexanone (1mmol); Ethanol (1ml); 0.05 mol%
o
a
Pt, 10 bar H at 120 C. Initial reaction rate of formation of the acetal.
2
b
-1
Calculated as mol of product/mol Pt xh
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Table 5. Reductive amination of EL with different amines using 0.2%Pt/TiO2D catalyst.
EL
Conv.(%)
98
Pyrrolidone
Select.(%)
95
Pyrrolidone
Yield (%)
93
Entry
1
Amine
t (h)
a
aniline
aniline
6
18
4
6
6
6
6
6
6
6
2
2
2
2
2
2
6
2
2
6
2
6
2
4
2
a
2
100
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78.1
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95
91
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90
99
97
88
75
98
96
98
61
94
92
53
100
28
100
16
40
26
37
90
90
50
90
87
82
81
85
90
94
83
62
98
92
90
49
91
79
35
b
3
aniline
4
5
6
7
8
2-methylaniline
2-ethylaniline
42
28
2-isopropylaniline
4-ethylaniline
40
97
4-methylaniline
4-methylaniline
4-methoxyaniline
4-cloroaniline
91
b
9
63.9
99
1
1
0
1
91
12
4-cyanoaniline
4-acetylaniline
4-vinylaniline
90
1
1
1
1
3
4
5
6
90
94
phenylmethylamine
2-phenylethylamine
butylamine
91
97
17
94
1
1
2
2
8
9
0
1
hexylamine
98
octylamine
100
95
2-hydroxyethylamine
3-hydroxypropylamine
cyclopentylamine
cyclohexylamine
cyclohexylamine
cycloheptylamine
92
22
80
2
3
97
b
2
4
86.6
67
2
5
Reaction conditions: EL (2 mmol), amine (2 mmol), hydrogen (P=10 bar), 100 mg 0.2%Pt/TiO2D
o
a
o
b
catalyst (0.05 mol%), S/C= 2000, at 120 C without solvent. 5bar at 150 C; Results reported
in ref 10. Reaction conditions: EL:amine:dioxane (wt%) = 0.30:0.25:0.50g, 50 mg of
o
commercial 5%Pt/C (ESCAT-248), S/C = 0.15, 150 C, hydrogen (55-69 bar).
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