Reductive amination of aldehydes and amines with an efficient Pd/NiO catalyst

Article abstract of DOI:10.1080/00397911.2013.857690

By applying a simple Pd/NiO catalyst, the reductive amination of amines and aldehydes can progress efficiently under mild reaction conditions, and 24 substituted amines with different structures were synthesized with up to 98% isolated yields.

Full text of DOI:10.1080/00397911.2013.857690

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Reductive Amination of Aldehydes and Amines with an
Efficient Pd/NiO Catalyst
Huimin Yang a b , Xinjiang Cui a , Youquan Deng a & Feng Shi a
a Centre for Green Chemistry and Catalysis , Lanzhou Institute of Chemical Physics, Chinese
Academy of Sciences, No.18, Tianshui Middle Road , Lanzhou , 730000 , China
b University of the Chinese Academy of Sciences , Beijing , 100049 , China
Accepted author version posted online: 02 Dec 2013.Published online: 02 Dec 2013.
To cite this article: Synthetic Communications (2013): Reductive Amination of Aldehydes and Amines with an Efficient Pd/NiO
Catalyst, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, DOI:
10.1080/00397911.2013.857690
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Feng Shi
Reductive Amination of Aldehydes and Amines
Reductive Amination of Aldehydes and Amines with an Efficient Pd/NiO Catalyst
Huimin Yang1,2, Xinjiang Cui1, Youquan Deng1, Feng Shi1,
1Centre for Green Chemistry and Catalysis, Lanzhou Institute of Chemical Physics,
Chinese Academy of Sciences, No.18, Tianshui Middle Road, Lanzhou, 730000, China,
2University of the Chinese Academy of Sciences. Beijing, 100049, China
Address correspondence to Feng Shi E-mail: fshi@licp.cas.cn
GRAPHICALABSTRACT
Abstract
By applying a simple Pd/NiO catalyst, the reductive amination of amines and aldehydes
can be progressed efficiently under mild reaction conditions. 24 substituted amines with
different structures were synthesized with up to 98% isolated yields.
KEYWORDS: Amination; aldehydes; amines; palladium
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INTRODUCTION
The formation of N-alkyl amines is one of the most important transformations in organic
chemistry1-2. In particular, N-alkyl amines are important building blocks for natural
products, pharmaceuticals and agrochemicals. The reaction of amines and alkyl halides
with the addition of stoichiometric amounts of inorganic bases is the most effective and
universal method3-5. However, this method often suffers from drawbacks such as usage of
toxic substrates and generation of inorganic salt waste. Moreover, various methods have
been developed for the synthesis of N-alkyl amines such as amination of alcohols6-9, the
reaction of amines with amines, hydroaminations10-16, and hydroaminomethylation17-21
Reductive amination is a general and attractive reaction for the synthesis of N-alkyl
amines which includes two synthetic steps: C=N double-bond formation and
.
hydrogenation of the imine derivatives. The traditional protocol for reductive amination
is based on the use of stoichiometric amount of boron hydrides 22-27. In order to develop
clean and economic way for the reductive amination reaction, the applying of molecular
hydrogen as reducing agent in the presence of homogeneous Pd or Ru catalysts was
developed successfully28-30. However, the using of homogeneous catalyst system faces
problem in catalyst-product separation and catalyst recycling. Heterogeneous catalysts
have innate advantages, such as ligand-free, easy isolation and catalyst reuse31-34. If
taking these advantages into account, the exploration of reductive amination reaction with
heterogeneous catalyst is highly desirable 35-40
.
Although good results were obtained, the known heterogeneous catalyst system is limited
by the relatively poor generality or rigorous reaction conditions. Here, we report an
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effective Pd/NiO, which was an active catalyst for nitrobenzene hydrogenation41, for the
reductive amination reaction under hydrogen atmosphere and at room temperature.
RESULTS AND DISCUSSION
The structure of the catalysts were characterized by TEM and HR-TEM (Figure 1), which
suggested that the palladium particles were well dispersed and the average size of the
palladium particles in Pd/NiO was about 5 nm (Figure 1a ). The Pd (111) crystal lattice
can be clearly observed from the HR-TEM picture (Figure 1b). The XRD diffraction
patterns of NiO suggested that it was a better-crystallized structure and obvious Ni (111),
(200), and (220) peaks were observed (PDF-87-0712). The introduction of palladium
didn’t change the crystal structure of NiO. Moreover, there was no observable diffraction
peak of palladium which suggested that the palladium species were highly dispersed over
the NiO support. XPS analysis showed that typical binding energies of NiO (854.3 eV)
and Pd (335.4 eV). According to ICP-AES analysis, the palladium loading is 1.1 wt%.
Initially, the reductive amination of benzaldehyde and aniline was used as the model
reaction for reaction conditions optimization under 1 atm hydrogen using Pd/NiO as
catalyst42. The solvents were optimized first (Table 1). Clearly, benzotrifluoride,
acetonitrile and dichloromethane are suitable solvents for the reaction (Entries 1-3). The
yields to N-benzyl aniline were 33-69% with >90% aniline conversions. The major
byproduct is the imine without being hydrogenated. Possibly, these solvents are
unfavorable for the imine hydrogenation. In reverse, lower conversions were obtained
with high N-benzyl aniline selectivities if acetone, THF and methanol were used as the
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solvents (Entries 4-6). The selectivities in these reactions were >90% but the aniline
conversions were 41-89%. According to GC-MS analysis, it was found that large amount
of toluene was generated via benzaldehyde hydrogenation, which resulted in the lower
conversion of aniline. Better results were obtained if toluene, xylene, isopropanol and
ethanol were used as the solvents (Entries 7-10). Although trace amount of imine and
toluene are detectable in these cases, the yields to N-benzyl aniline reached 89-91%. If
the reaction time was prolonged, relatively lower yield was obtained, which suggested
that the reaction was reversible and small amount of N-benzyl aniline was
dehydrogenated (Entry 11). Similarly, higher reaction temperature or catalyst loadings
resulted in lower yields, too, due to the hydrogenation of benzaldehyde to toluene
(Entries 12-14). Although good result was also gained with lower catalyst loadings in the
reductive amination of aniline and benzaldehyde, (Entries 15-16), the applying of lower
catalyst loadings caused poor generality in the reductive amination of other compounds.
Therefore, 20 mg catalyst was used for the next exploration.
According to the above discussions, the optimized reaction conditions, i.e. 1 mmol amine,
1 mmol aldehyde, 20 mg catalyst, 2 mL ethanol, r.t. and 12 h, were used in the generality
testing. As shown in Table 2, the reductive amination of benzaldehyde with aniline and
1-naphthylamine can obtain desired products in good yield of 84% and 88% (Entries 1
and 2). Benzylamines with electron-withdrawing and electron-donating groups can also
be converted into the desired products in good to excellent yields (Entries 3-6).
Interestingly, the reductive amination reactions of benzaldehyde with primary amines
containing different heterocyclic ring structures, i.e. pyridin-2-amine,
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furan-2-ylmethanamine and 2-(piperazin-1-yl)ethanamine, can progress well with up to
98% isolated yields (Entries 6-8). Excellent results were also obtained if aliphatic amines
such as butan-1-amine, heptan-1-amine dodecan-1-amine were used as the starting
materials (Entries 9-11). The yields to the aim products all reached 98% in the reactions
of benzaldehyde with typical secondary amines 1-phenylethanamine and
cyclohexanamine (Entries 12-13).
Next, aldehydes with different structures can react with aniline to give the desired
products, too (Table 3). Irrespective of the structure and position of the substituting
groups, good to excellent yields, i.e. 87-98%, of the corresponding products were
obtained (Entries 1–9). Thus there were no remarkable steric and electronic effects on the
reactivity of the aromatic aldehydes. Noteworthy, 95% of the corresponding product was
obtained when furan-2-carbaldehyde was used (Entry 10). Typical aliphatic aldehyde, i.e.
butaldehyde, can also be converted into the desired N-benzyl butyl amine successfully
with 98 % yield under this reaction conditions (Entry 11).
Moreover, in order to see if the dissolved catalytic species from Pd/NiO catalyzed the
reaction or not, after the first run, 1.0 mmol aniline and 1.0 mmol benzaldehyde were
added into the reaction solution again after removing the catalyst. However, there is no
any observable N-benzyl aniline formation by GC-FID after it was reacted for another 12
h. These results excluded the possible contribution of homogeneous catalytic species
leached from Pd/NiO catalyst. Finally, the reusability of the Pd/NiO catalyst was tested.
The catalyst can be easily separated from the mixture solution by centrifugation. Then the
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catalyst was washed by ethanol for two times and reused directly without other treatment.
Clearly, the catalyst showed high catalytic activity on the reductive amination of
benzaldehyde and aniline even if the catalyst was reused at the fifth run (Table 4). It
suggests that the catalyst is reusable potentially.
EXPERIMENTAL
Preparation Of The Nio Nanoparticles
The catalyst samples were prepared starting from sol-gel polymerization of resorcinol
and formaldehyde with Na2CO3 as a catalyst with 50%Ni-doped monolithic carbon
aerogels. Typically, resorcinol (2.20 g, 20 mmol), formaldehyde (3.25 g, 40 mmol, 36.5%
in water, methanol stabilized) and 6 mL distilled water were added into a 100 mL PTFE
autoclave and the mixture was stirred for 0.5 h. Subsequently, an aqueous solution of 5.8
g Ni(NO3)2•6H2O was added dropwise and a 0.9M solution of Na2CO3 (4 mL)were added
into the mixture. After vigorous stirring for 1 h, the autoclave was sealed and kept at 80
oC for 1 day. Then the autoclave was cooled to room temperature. The wet gels were
placed into a round-bottomed flask and vacuum dried at 130 oC for 3 h. After being
pyrolyzed at 800 oC for 5 h in nitrogen flow (20 mL/min), about 7 g black solid was
obtained. Then the black solid was treated at 500 oC for 5 h in a flow of oxygen (20
mL/min) to afford the NiO nanoparticles (about 4.1 g).
Preparation Of Pd/Nio Catalysts
Pd that was supported on NiO was prepared according to a solimmobilization method.
For the 1.1 wt% Pd/NiO catalyst, the detailed preparation procedure employed is
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described below. 0.067 ml an aqueous solution of H2PdCl4 (0.067 mL, 35 mg mL-1) was
added to distilled water (5 mL). Then, an aqueous solution of PVA (1.2 mL, 5mgmL-1)
was added. After 30 min, a freshly prepared 0.1 M solution of NaBH4 (NaBH4 /Pd, 4:1
mol/mol) was then added to form a dark-brown sol. After 30 min of sol generation, the
colloid was immobilized by adding NiO powder (100 mg). The solution was acidified to
pH 1 by sulfuric acid under string conditions and was stirred for another 2 h finally. The
resulting solid was washed with distilled water (3×40 m L) and was dried in air at 80 oC
for 2 h to afford the Pd/NiO catalyst.
Reductive Reaction Of Aldehydes And Amines
1.0 mmol amine, 1.0 mmol aldehyde, 2 mL solvent and 20 mg catalyst were added in a
40 mL reaction tube. The above mixture were reacted at 25 oC and under hydrogen
atmosphere for 12 h. After the reaction, the reaction mixture was detected by GC-MS.
The aimed product was obtained by TLC and analysis by NMR.
CONCLUSION
In conclusion, we have developed a simple Pd/NiO catalyst system for the reductive
amination reaction under mild reaction conditions. The Pd/NiO catalyst exhibited
excellent activity and selectivity in the reductive amination reaction using various amines
and aldehydes as the substrates. In addition, the Pd/NiO catalyst can be easily recycled
for several runs without deactivation.
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SUPPLEMENTAL MATERIAL
Supplemental data for this article can be accessed on the publisher’s website. the
publisher’s website will be a live link
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China (21073208) and Chinese
Academy of Sciences for financial support
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Representative procedure for the reductive amination reactions of aldehydes
and amines: 1.0 mmol amine, 1.0 mmol aldehyde, 2 mL solvent and 20 mg catalyst were
added into a 40 mL reaction tube. The above mixture was reacted at 25 oC and under
hydrogen atmosphere for 12 h. Then, the reaction mixture was filtrated to remove the
catalyst. Pure products can be obtained simply after removing the solvent and other
impurities using rotary evaporator and vacuum drying. All the products were analyzed by
GC-MS and 1H NMR.
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Table 1. Optimization of reaction conditionsa
Entry Solvent
T/oC Cat./ mg t/h Conv./ %b Sel./ %b Y./ %c
Benzotrifluoride 25
Acetonitrile 25
Dichloromethane 25
1
20
20
20
20
20
20
20
20
20
20
20
20
20
5
10 94
10 90
10 95
10 89
10 80
10 41
10 94
10 93
10 95
10 95
12 91
12 77
12 65
12 91
12 97
12 80
73
64
35
96
96
92
95
96
96
95
95
95
94
96
96
95
69
58
33
85
77
38
89
89
91
90
86
71
61
87
93
76
2
3
4
Acetone
THF
25
25
25
25
25
25
25
25
50
75
25
25
25
5
6
MeOH
Toluene
Xylene
Isopropanol
EtOH
7
8
9
10
11
12
13
14
15
16
EtOH
EtOH
EtOH
EtOH
EtOH
10
30
EtOH
aReaction conditions: benzaldehyde (1.0 mmol), aniline (1.0 mmol), Pd/NiO (20 mg,
0.2 mol% Pd to aniline), under hydrogen atmosphere, solvent (2 mL).
bConversion of aniline. Selectivity to N-benzyl aniline.
cGC yield determined by GC-FID using biphenyl as external standard material.
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Table 2. Reductive amination of benzaldehyde with various aminesa
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Table 3. Reductive amination of aniline with various aldehydesa.
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Table 4. Recycling exploration of Pd/NiOa.
Run
1st
2nd
90
3rd
89
4th
87
5th
91
Yield[%]b 88
aReaction conditions: benzaldehyde(1.0 mmol), aniline(1.0 mmol),
Pd/NiO (20 mg) and solvent (2 mL), under hydrogen atmosphere, 12 h, 25 oC.
bGC yield.
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Figure 1. TEM and HR-TEM pictures of Pd/NiO (scale bar: a. 20 nm; b. 5 nm).
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