Heterogeneous Catalyzed Chemoselective Reductive Amination of Halogenated Aromatic Aldehydes

Article abstract of DOI:10.1002/cctc.202100334

The chemoselective conversion of a specific functional group in a multifunctional substrate is of great importance in the chemical industry to obtain cost efficient, sustainable and waste free processes. This work focuses on the chemoselective amination of halogenated aromatic aldehydes with dimethyl amine towards halogenated aromatic amines, a raw material used in the production of for example agrochemical active ingredients. It was found that by combining palladium, a metal known for dehalogenation reactions, and copper, known for its direct hydrogenation of aldehydes to alcohols, in one heterogeneous bimetallic catalyst, a synergistic effect is obtained. By depositing copper onto a palladium on carbon catalyst with a Cu/Pd ratio of at least 1 : 1, the yield could be increased from 66 % (Pd/C) to 98 % (PdCu/C). Moreover, this highly active and stable catalyst also showed suppressed dehalogenation side-reactions in several other chemical conversions such as hydrogenation of nitro functional groups and hydrogenation of aldehydes.

Full text of DOI:10.1002/cctc.202100334

The European Society Journal for Catalysis
Supported by
Accepted Article
Title: Heterogeneous catalyzed chemoselective reductive amination of
halogenated aromatic aldehydes
Authors: Kim Naz Rose-Marie Dumoleijn, Alberto Villa, Marcello
Marelli, Laura Prati, Kristof Moonen, and Christian. V. Stevens
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To be cited as: ChemCatChem 10.1002/cctc.202100334
Link to VoR: https://doi.org/10.1002/cctc.202100334
01/2020

10.1002/cctc.202100334
ChemCatChem
FULL PAPER
Heterogeneous catalyzed chemoselective reductive amination of
halogenated aromatic aldehydes
Ing. Kim N. R. Dumoleijn,*[b] Prof. Dr. AlbertoVilla,[c] Dr. Marcello Marelli,[d] Prof. Dr. LauraPrati,[c] Dr.
Kristof Moonen,[b] Prof. Dr. Christian. V. Stevens[a]
[a]
SynBioC Research Group, Department of Green Chemistry and Technology, Facultyof Bioscience Engineering
Ghent University
Coupure Links 653, 9000 Ghent, Belgium
E-mail: chris.stevens@ugent.be
[b]
[c]
[d]
Eastman Chemical Company
Pantserschipstraat207, 9000 Ghent, Belgium
E-mail: kimdumoleijn@eastman.com
Dipartimento di Chimica
Università degli Studi di Milano
Via C. Golgi 19, 20133 Milan, Italy
National Research Council
CNR-SCITEC
Via G. Fantoli 16/15, 20133 Milan, Italy
Abstract: The chemoselective conversion ofa specificfunctional
group in a multifunctional substrate is of great importance in the
chemical industry to obtain cost efficient, sustainable and waste
free processes. This work focuses on the chemoselective
amination of halogenated aromatic aldehydes with dimethyl
amine towardshalogenated aromaticamines, a rawmaterialused
in the production of f.e. agrochemical active ingredients. It was
found that by combining palladium, a metal known for
dehalogenation reactions, and copper, known for its direct
hydrogenation of aldehydes to alcohols, in one heterogeneous
bimetallic catalyst, a synergistic effect is obtained. By depositing
copper onto a palladium on carbon catalyst with a Cu/Pd ratio of
at least 1:1, the yield could be increased from 66 % (Pd/C) to 98 %
(PdCu/C). Moreover, this highly active and stable catalyst also
showed suppressed dehalogenation side-reactions in several
other chemical conversions such as hydrogenation of nitro
functionalgroupsand hydrogenation of aldehydes.
selectivityin the hydrogenation of aldehydes/ketones,[2] aromatic
[6]
rings,[3] carboxyl groups,[4] nitrile groups,[5] nitro groups,
quinoline components[7] and olefins[8] while concurrent
dehalogenation reactions are suppressed. However, limited
research was done to develop a chemoselective route for the
catalytic(reductive)amination in the presence of a halogen atom,
despite the importance of this class of compounds in different
applications.[9] Some examplesof (reductive) amination reactions
of halogenated substrates could be found when the substrate
scope of a newly developed catalyticmethod was broadened,[6a,
6b, 10]
but limited research really had the intention to find and
optimize an industrially feasible route towards halogenated
amines through a (reductive) amination reaction. Hizartzidiset al.
utilized flow chemistry in combination with a Pt/C catalyst to
increase the chemoselectivity of the reductive amination of
halogenated benzaldehydesbut low throughputs were achieved.
[11] In previouslyreported research we changed the propertiesof
a palladium on carboncatalyst by calcination in order to decrease
the amount of dehalogenation reactions.[12] Although good yields
were obtained with this method, diluted conditions were used
which limit the industrial feasibility of this route due to increasing
solvent recuperation costs. Moreover, besides dehalogenation
reactions, several other side reactions can occur such as direct
hydrogenation of the aldehyde or substitution of the halogen by
the amination agent. These side products also complicate the
industrial process and increase purification costs. The research
reported in this paper focuses on the modification of the metal
catalyst composition as a wayto achieve an industrially applicable
reductive amination processfor halogenated aldehydes.
Introduction
The transformation of a specific functional group in
a
multifunctional substrate is of great importance in the chemical,
pharmaceuticaland agrochemical industry.[1] Halogen atomsare
often used as reactive groups next to other functional groups in
precursorsand intermediatesforactive ingredientswhich can be
easily transformed via different (chemical) methods.
Chemoselective hydrogenation reactions of various functional
groups in the presence of halogens are therefore widely
discussed. Several methods are described for enhancing this
1
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reaction time. While the catalysts based on palladium (Entry1 and
2, Table 1) show a lot of dehalogenation activity, both copper
catalysts (Entry9 and 10, Table 1) and platina catalysts(Entry 5
and 6, Table 1) lead to more aldehyde hydrogenation reactions
yielding the alcohol 5. In this series of tested catalysts, only the
nickel-based catalysts(Entry7, Table 1) showa high tendencyof
both the dehalogenation reaction and the aldehyde hydrogenation
reaction towardsthe alcohol.
Results and Discussion
In exploratory experiments, we selected the reductive amination
of 2-chlorobenzaldehyde (1) with dimethyl amine to the
corresponding 2-chlorobenzyl N,N-dimethyl amine (2) as the
model reaction to study the activity and selectivity of different
catalysts for the chemoselective reductive amination of
halogenated benzaldehydes. Obtaining compound 2 without the
C-Xbond cleavage (by hydrogenolysis)and directhydrogenation
of the aldehyde is of high importance as both the amine and the
halogen functional group are further utilized forf.e. the synthesis
of chloromethylphenylglyoxylic esters, an important intermediate
for the production of agrochemical active ingredients.[13]
Interestingly, it was observed that when a palladium on carbon
catalyst wasused after a run with a copper sponge catalyst (Entry
11, Table 1), less dehalogenation reaction was observed in
comparison with runs with a ‘clean’ palladium catalyst (Entry 1
and 2, Table 1). Postmortem analysis of this catalyst showed
besides palladium, also copperonto the activated carbon support.
It is believed that Cu(II) salts were left behind onto the reactor
surface due to leaching of the sponge copper catalyst. When the
palladium on activated carbon was used, these salts adsorbed
onto the catalyst surface forming a bimetallic palladium-copper
catalyst. When using thisbimetalliccatalystwhich contained both
palladium, a metal with a high tendency for dehalogenation
reactionsand copper, a metal with a high tendency for aldehyde
hydrogenation reactions, both side reactions are suppressed
simultaneously. This synergistic effect between Pd and Cu is
reported earlier in several different type of reactions with
halogenated substrates but was unprecedented for reductive
amination reactions. Goulas et al. reported Pd-Cu alloy formation
in a bimetallicPd-Cuon hydrotalcite-carbon (HT-C) catalyst which
increased the selectivity in oxygenate coupling reactions.[14]
Bonarowska showed the effect of copper addition to supported
palladium on the catalytic performance on hydroisomerization of
n-pentane. Again, Pd-Cu alloy formation was seen as the main
reason for the improved selectivity.[15]
First, a variety of commercially available heterogeneous metal
catalysts were screened to investigate their impact on both the
dehalogenation reaction (yielding 3), substitution reaction
(yielding 4)and the direct hydrogenation reaction (yielding 5). The
amine to 2-chlorobenzaldehyde ratio was kept constant (unless
mentioned otherwise) and a catalyst amount of 2 wt.% was used
regardless of the metal loading. Either methanol or water were
used as solvent. It hasto be mentioned howeverthat, since water
is liberated in the amination reaction, water will influence the
equilibriumof the intermediaryiminium ion/hemi-aminal formation
and thus potentially affect the overall reaction rate. Since the
reaction was ran in almost all cases to complete conversion, the
effect of water onto the overall reaction rate, could not be
assessed. Both the conversion of the aldehyde and the molar
yields of the different formed reaction products were calculated
based on GC data. The screening results are summarized in
Table 1 and Table S1. The data obtained shows some clear
trends between the choice of the metal in the catalyst and the
yields of the main and side products. Most catalysts (except
Raney® Co) show almost complete conversion after 3 hours
Table 1. Hydrogenation of 2-chlorobenzaldehyde under different conditionsa
Entry
Catalyst
Solvent
t (h) Conversion
(%)
Yield
2 (%)
Yield
3 (%)
Yield
4 (%)
Yield
5 (%)
1a
1b
2a
2b
3
3 % Pd/C
3 % Pd/Cb
H2O
H2O
2
2
2
2
5
3
>99
>99
>99
>99
>99
>99
64
70
62
69
88
47
21
15
35
28
<1
1
8
<1
<1
<1
<1
3
10
<1
<1
3
0.5 % Pd/C
H2O
0.5 % Pd/C
MeOH
H2O
5 % Pd-Pb/CaCO3
5 % Ru/C
4
H2O
13
20
2
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5
6
3 % Pt/C
5 % Pt/C
Raney®Ni
H2O
H2O
3
3
3
3
3
6
3
3
3
3
3
>99
>99
>99
>99
>99
89
72
82
9
1
<1
1
10
8
7
1
7a
H2O
1
50
28
9
7b
7c
Raney®Ni + borax
Raney®Ni + HAc
H2O
52
64
10
80
86
91
92
93
7
1
H2O
13
1
1
8
Raney®Co
H2O
15
7
23
8
9
Raney®Cu 2900
H2O
98
<1
<1
<1
4
10a
10b
11a
11b
Sponge Cu (A3B00)
Sponge Cu (A3B00)
3 % Pd/C + traces sponge Cu
3 % Pd/C + traces sponge Cu
H2O
>99
>99
>99
>99
<1
<1
<1
<1
13
7
MeOH
H2O
1
MeOH
3
<1
a Reaction conditions:T = 373 K; 5 MPa H2 pressurized atroom temperature; 1.5h reaction time; 1 g solvent/g o-Cl-BZA; 1.5 eq. dimethyl amine;2 wt.% catalyst
b 3 eq. dimethyl amine
Table 2. Effect of the metal ratio and support of Pd-Cu catalysts on the reductive amination of 1 with dimethyl aminea,b
Entry
Catalyst
Pd (%)
Cu (%)
Metal area
(m²/g)
Yield
2 (%)
Yield 3
(%)
Yield
4 (%)
Yield 5
(%)
Conversion
(%)
1
2
Pd/Cc
Pd-Cu1/Cc
Pd-Cu2/Cc,e
2.95
2.94
2.86
2.63
0.90
2.36
n.d
n/a
1.85
3.55
6.50
3.80
11.82
n.d.
15.0
6.8
>99
66
98
98
99
99
99
90
96
19
1
8
0.2
0.2
0.4
0.4
0.4
0.4
4
>99
>99
>99
>99
>99
>99
>99
0.1
0.2
0.3
0.2
0.2
1
3
3.0
0.8
0.2
<0,1
0.4
6
4a
4b
5
Pd-Cu4.2/Cc,f
Pd-Cu4.2/Cd
Pd-Cu8.4/Cc,e
Pd-Cu4.2/aluminac
Pd-Cu4.2/silicac
4.0
n.d.
3.3
6
n.d.
7
n.d
n.d.
n.d.
2
0.8
2
a Reaction conditions:T = 373 K; 7 MPa H2 pressurized atroom temperature; 1.5h reaction time; 0.3 g MeOH/g o-Cl-BZA;1.5 eq. dimethyl amine; 0.5 mg
catalyst/g substrate
b n.d. = not determined
c a Pd loading of 3 wt.% is used
d a Pd loading of 1 wt.% is used
e average of two experiments
f average of four experiments
Encouraged by these results, several different bimetallic
palladium/copper catalystson activated carbonwere prepared on
purpose using the precipitation method starting from a pre-made
palladium on carbon catalyst (unless mentioned otherwise) and
copper nitrate. All reactions were performed in MeOH at 100 °C
and 7 MPa hydrogen atmosphere. In view of the catalyst
application, research was first done on finding the optimum
activation procedure for the bimetallic Pd-Cu/C catalysts since
Cu(II) species will be present in a freshly synthesized catalyst.
The results are given in Table 4S. It was seen that by activating
the catalyst in methanol at 180 °C under a 3 MPa hydrogen
atmosphere, the highest yield towards the wanted compound 2
was obtained. It isbelieved that this activation procedure willallow
the reduction of allthe Cu(II) speciesinto the active Cu(0)species
to have a better interaction between the palladium-copper
particles and thusminimize dehalogenation reactions. Performing
a reductive amination experiment with a non-activated Pd-Cu4.2/C
catalyst already gives lower amounts of dehalogenation reaction
compared to a Pd/C catalyst (Entry1a, Table 4Sversus Entry 1,
Table 2). Togetherwith the observation that a second consecutive
run with a non-activated Pd-Cu4.2/C catalyst results in a lower
amount of dehalogenation reaction compared to a first run (Entry
1a and 1b, Table 4S), it is believed that even at the reaction
temperature, part of the Cu(II) species can be reduced towards
Cu(0) and therefore, already have beneficial effects on
suppressing the dehalogenation reactions. Roma et al. have
indeed showed that the reduction of Cu(II) species isfacilitated in
the presence of Pd.[16] The results of the reductive amination
reactions with different bimetallic Pd-Cu/C catalysts are given in
Table 2 and Table S2. While a monometallic Pd on carbon
catalyst resulted in a large amount of dehalogenation reaction
(Entry 1, Table 2), switching to a catalyst composed of a 1:1
Pd:Cu molar ratio suppressed the dehalogenation reactions
significantly (Entry 2, Table 2). Increasing the Cu amount to an
atomic ratio of 4.2 even lowered the dehalogenation reaction
down to 0.2 % resulting in a yield of 99 % towards the desired
halogenated amine 2. Although pure Cu catalysts result in
3
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10.1002/cctc.202100334
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significant amounts of direct aldehyde hydrogenation reactions,
this was not the case when combined with Pd.
as high compared to the tested Pd-Cu alloys (99 %), there are a
few other metal combinations that show a significant increased
selectivity towards the reductive amination of 2-chloro-
benzaldehyde and a reduced levelofdehalogenation reactions in
comparison with a monometallic Pd on carbon catalyst while
maintaining a proper level of activity. A Pd-Ag alloy with a 1:2
atomic ratio could decrease the dehalogenation reactions below
5 % and increase the yield towards the wanted halogenated
amine 2 to 94 % (Table 3, Entry 4). A Pd-Re alloy and a Pd-Mo
alloy lead to a yield of 2 of respectively 87 % and 93 % (Table 3,
Entry 9 and 11). Although very little dehalogenation activity was
also seen for Pd-Rh, Pd-Ru, Pd-Pb and Pd-Sn alloys, the yield
towards the aminated halogenated product was also very low.
Other, unidentified side-productswere formed instead. In this Pd
based bimetalliccatalyst study, a Pd-Cu alloywith an atomicratio
of 1:4.2 gives the best results, both in terms of selectivity and
activity.
To better understand the effect of the copper addition on the
catalyticactivity, the morphologyof selected Pd-Cu catalystswas
investigated by using transmission electron microscopy (TEM)
and X-Ray diffraction (XRD). TEM showed that the average
particle size of all Pd-Cu/C catalysts are in the range of 3-4 nm
with a narrowparticlesize distribution forPd-Cu2/C (Figure S1b),
whereas for Pd-Cu4,2/C also particles larger than 10 nm were
detected (Figure S2b). STEM-EDX analysis of Pd-Cu2/C
confirmed the presence of Pd and Cu with an average Pd:Cu
content of 3.07%-3.34% (Figure S1C, spectrum 2) similar to the
nominal one of 2,86%-3,55% (Entry 3, Table 2). However large
aggregates (Figure S1C, spectrum 3) enriched in Pd were
detected. STEM-EDX analysis of Pd-Cu4.2/C showed a lower
content of Cu compared to the nominalone (calculated Pd-Cu of
3.12%- 5.47%; nominal of Pd-Cu of 2.63%- 6.50%). XRD was
also performed on Pd-Cu2/C and Pd-Cu4.2/C to understand the
nature of the catalyst. XRD pattern showed the presence of a
bimetallicstructure (alloy) but also the presence of segregated Pd
and Cu species(Figure S3).
Table 3. Effect of a second metalin a bimetallic palladium on
carbon catalyst on the reductive amination of 1 with dimethyl
aminea
Entry
Catalyst
conversion
Yield 2
(%)
55
Yield 3
(%)
35
37
37
2
(%)
>99
>99
>99
98
Besides copper, it is known that other metals can also form an
alloy when combined with palladium and beneficial effectsof this
alloying in hydrogenation reactions have been observed forf.e.
Pd-Ag,[17] Pd-Au,[17d, 18] Pd-Ru,[6c, 18b, 19] Pd-Zn,[20] Pd-Pb,[21] Pd-
Re,[22] etc. In order to investigate the potential of other bimetallic
palladium on carbon catalysts in the chemoselective reductive
amination of halogenated aldehydes, several different Pd-metal
catalysts were prepared and tested in the benchmark reductive
amination reaction shown in Table 1. Similar catalyst synthesis
proceduresand reduction procedureswere used as for the Pd-Cu
catalysts. The results are given in Table 3 and Table S3. The
molar ratio of the second metal isgiven in the subscript. Although
none of the tested bimetallicPd-metalcatalystsgivesa selectivity
1
2
Pd-Fe2/C
Pd-Ni2/C
Pd-Co2/C
Pd-Ag2/C
Pd-Rh2/C
Pd-Ru2/C
Pd-Pb2/C
Pd-Sn2/C
Pd-Re2/C
Pd-Au2/C
Pd-Mo2/C
53
3
53
4
94
5
88
78
2
6
83
23
<1
<1
<1
7
7
60
27
8
66
13
9
95
87
10
11
97
82
14
3
97
93
a Reaction conditions:T = 373 K; 7 MPa H2 pressurized atroom temperature;
0.3 g MeOH/g o-Cl-BZA;1.5 eq. dimethyl amine; 0.5 mgcatalyst/g substrate;
1.5 h reaction time;
Table 4. Hydrogenation of alternative substrateswith Pd-Cu bimetallic catalysta
Entry
Substrate
Product
Catalyst
conversion
(%)
Yield product (%)
Yield dehalogenated
product (%)
Pd/C
40
37
5
21
8
1
Pd-Cu4.2/C
22
Pd/C
Pd-Cu4.2/Cb
97
11
98
65
11
92
33
<1
7
2
Pd-Cu4.2/C
4
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Pd/C
>99
>99
<1
81
88
16
3
Pd-Cu4.2/C
Pd/C
>99
>99
62
96
31
1
4
5
Pd-Cu4.2/C
Pd/C
>99
>99
66
95
30
1
Pd-Cu4.2/C
a Reaction conditions:T = 373 K; 7 MPa H2 pressurized at roomtemperature; 0.3 g MeOH/g o-Cl-BZA; 0.5 mg catalyst/g substrate; 1.5 h reaction time;
b temp = 50 °C
To showthe industrialapplicabilityof the most selective catalyst,
the bimetallicPd-Cu4.2/C, the long-termstabilitywas investigated
in repeated amination reactions of 2-Cl-benzaldehyde with
dimethyl amine. A total of 15 consecutive recycling tests were
carried out by reusing the catalyst by filtration without anyfurther
intermediate purification or activation. The result of this test,
shown in Figure 1, highlights the excellent reusability of this
catalytic system. Both selectivity and activity are maintained
throughout the consecutive runs. Moreover, Inductively Coupled
Plasma (ICP) analysis of the reaction mixtures after each
consecutive run revealed no leaching of palladium (<0.2 ppm) or
copper(<0.2 ppm)into the reaction mixture.
aminated product could be increased from below1 % up to 81 %
(Table 4, Entry 3) when using a Pd-Cu catalyst instead of a pure
Pd catalyst.
Conclusion
In summary, an efficient method was found for the
chemoselective reductive amination of
halogenated
benzaldehyde. By combining palladium, a metal known for
dehalogenation reactionsand copper, a metalknown forthedirect
reduction of aldehydes, a highly active, selective and stable (15
consecutive runs) catalyst was found for these conversions. The
dehalogenation reaction could be suppressed almost completely.
Conversionsand selectivities as high as 99 % could be obtained
in the case of 2-chlorobenzaldehyde and dimethyl amine.
Moreover, a clear effect was seen of the Pd:Cu ratio used in the
final catalyst on the ratio of the desired reductive amination
reaction and the unwanted dehalogenation reaction. When
comparing to the other methods used for suppressing the
dehalogenation reactionsduring a reductive amination reactions,
the process reported in the current research shows the highest
potential for an industrial process due to the high yields and the
low amount of solvents needed (in comparison with f.e. the
method developed by Villa et al.).[12] Besides reductive amination
reactions, it was also shown that this concept can be used forthe
chemoselective hydrogenation of other substrates such as nitro
functionalgroupsor aldehydes in the presence of halogen groups.
100
95
90
85
80
75
70
65
60
55
50
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15
Run
Figure 1. Stability tests using Pd-Cu4.2/C in the amination of 2-
Cl-benzaldehyde with DMA. Conversion: ♦; Yield of 2: ■
Furthermore, the applicability of the Pd-Cu catalytic system was
investigated forother hydrogenation reactions in the presence of
a halogen atom such as the hydrogenation of an aldehyde, the
hydrogenation of a nitro group and the reductive amination of
aldehydeswith different amination agents (Table 4). The positive
effect of the copperaddition to a palladium on carbon catalyst on
suppressing the dehalogenationreaction was confirmed in allthe
cases. Interestingly, with a bromo substituted aldehyde, very
prone for dehalogenation, the yield towards the halogenated
Experimental section
Catalyst preparation
The bimetallic Pd/metal on activated carbon catalyst were
synthesized starting from a palladium on carbon catalyst
(Pd/C), obtained from the company Johnson Matthey. A 10 g
L-1 aqueous suspension of the Pd/C is stirred continuously
while an aqueous mixture of 5 g L-1 of the chloride salt of the
metal is added slowly to the suspension at ambient
temperature. A sodium bicarbonate solution (35 g L-1) is then
5
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10.1002/cctc.202100334
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added dropwise until a pH of 8 is obtained. Hereafter, the
catalyst slurry is heated to 70 °C and stirred for 15 minutes.
After cooling down, the catalyst slurryis filtered, washed three
times with water and dried under vacuum. Prior to the
hydrogenation reaction, the catalyst was reduced at 180 °C in
MeOH at 3 MPa of hydrogen.
Hydrogenation of nitro compounds
In a typical experiment (and unless mentioned otherwise), a
50 mL autoclave (Parr®) was loaded with 20g of an nitro
compound obtained from the company Sigma Aldrich, a
specific amount of solvent (methanol) and the catalyst. The
reactor was sealed, and the gas phase was flushed three
times with nitrogen and then pressurized at 3 MPa by the
addition of hydrogen gas. The autoclave was heated to the
reaction temperature and hydrogen was added to the final
pressure. After a certain reaction time, the reaction mixture
was cooled down and degassed at room temperature.
Filtration of the reaction mixture was done to separate the
liquid reaction mixture from the solid catalyst.
Amination reaction of aldehydes with dimethyl amine/mono
methyl amine
In a typical experiment (and unless mentioned otherwise), a
300 mL autoclave (Parr®) was loaded with 90g of an aldehyde
obtained from the company Sigma Aldrich, a specific amount
of solvent (methanol in most cases) and a certain amount of
aminating agent (f.e. dimethyl amine). The reactor was sealed,
and the gas phase was flushed three times with nitrogen and
then pressurized at 0.5 MPa by the addition of nitrogen gas.
The reactor was heated until 80 °C and then continuously
stirred for 60 minutes at that temperature. After cooling down,
a certain amount of catalyst was added to the autoclave. The
autoclave was heated to the reaction temperature and
hydrogen was added to the final pressure. After a certain
reaction time, the reaction mixture was cooled down and
degassed at room temperature. The reductive amination
reaction was allowed to proceed for the indicated time at the
indicated reaction temperature. Filtration of the reaction
mixture was done to separate the liquid reaction mixture from
the solid catalyst. Recycling experiments were carried out
under the same experimental conditions. After each run, the
reaction mixture was removed from the reactor without
exposing the catalyst to air and new reagents and solvent
were added to the reactor.
Purification of compound 2
After the amination reactions, the reaction mixtures were
purified by rectification. The reaction mixture was transferred
into a 250 mL Sovirel® reactor equipped with a double jacked
heated with thermal oil, a stirrer, a thermocouple and a
rectification column containing 20 theoretical plates. A reflux
ratio of 4 was used in all cases and distillate samples were
taken regularly (every 10 mL).
Acknowledgements
The authorsthankEastman Chemical Company forsupport of this
work. We also especially would like to thank Patricia Janssens
(Eastman-Ghent) and Ria De Potter (Eastman-Ghent) for all the
analyticalhelp.
Keywords: alloyformation - chemoselectivity - dehalogenation -
heterogeneouscatalysis - reductive amination
Hydrogenation reaction of aldehydes
[1]
[2]
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Entry for the Table of Contents
Y: 70 %
Y: 90 %
Y: > 99 %
Cu Cu
Pd
Pd
Cu
Carbon Support
Cu
Cu
High chemo-selectivityis one of the key parametersfor the design of waste free and sustainable chemical processes. Thiswork
described the use of a stable bimetallicpalladium-copper catalyst for the selective reductive amination of halogenated aromatic
aldehydestowards tertiaryamineswith yieldshigher than 99 %.
8
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