Synthesis of amines by reductive amination of aldehydes and ketones using Co3O4/NGr@C catalyst

Article abstract of DOI:10.1002/cctc.201402527

Heterogenized non-noble metal-based catalysts allow for costefficient and environmentally benign hydrogenations. Here, we have developed a straightforward reductive amination methodology using molecular hydrogen in the presence of a Co₃O₄/ NGr@C catalyst system. Various carbonyl compounds were transformed with secondary amines to the corresponding tertiary amines with good to excellent yields and selectivity. The Co₃O₄/NGr@C catalyst is recycled up to five times without significant loss of activity.

Full text of DOI:10.1002/cctc.201402527

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DOI: 10.1002/cctc.201402527
Synthesis of Amines by Reductive Amination of Aldehydes
and Ketones using Co3O4/NGr@C Catalyst
Sabine Pisiewicz, Tobias Stemmler, Annette-Enrica Surkus, Kathrin Junge, and
Matthias Beller*[a]
Heterogenized non-noble metal-based catalysts allow for cost-
efficient and environmentally benign hydrogenations. Here, we
have developed a straightforward reductive amination meth-
odology using molecular hydrogen in the presence of a Co3O4/
NGr@C catalyst system. Various carbonyl compounds were
transformed with secondary amines to the corresponding terti-
ary amines with good to excellent yields and selectivity. The
Co3O4/NGr@C catalyst is recycled up to five times without sig-
nificant loss of activity.
Pt-, Ru-, Rh- and Cu-based catalysts are used occasionally.[5,6]
Notably, most of the previous work is concerned with the re-
ductive amination of carbonyl compounds using primary
amines, while the present work focusses on the synthesis of
tertiary amines.
Recently, we synthesized novel heterogeneous cobalt oxide
catalysts by pyrolysis of Co(OAc)2 and 1,10-phenanthroline on
Vulcan XC72R as carbon support. Pyrolysis at 8008C under
inert conditions led to active hydrogenation and oxidation cat-
alyst systems.[7] Regarding the catalyst structure, we observed
fractions of well pronounced cobalt-based nanoparticles with
varying sizes of 2–20 nm, as well as particles and agglomerates
in the range of 20–200 nm. Notably, these particles are encap-
sulated by individually nitrogen-enriched graphene-type
layers,[8] which are formed in the pyrolysis process by carboni-
zation of the nitrogen ligand. On the basis of this work, we
became interested to explore the resulting Co3O4/NGr@C ma-
terial in reductive amination reactions of carbonyl compounds
and secondary amines to give tertiary amines.
Tertiary amines are common motifs found in numerous organic
building blocks, industrial fine chemicals, agrochemicals and
pharmaceuticals. For their synthesis the direct reductive amina-
tion (DRA) of carbonyl compounds is an efficient and straight-
forward method.[1] It allows the formation of a variety of substi-
tuted amines starting from easily available carbonyl com-
pounds. Typically, the process is performed as a one pot reac-
tion with imines, enamines, or iminium cations as intermedi-
ates followed by subsequent reduction (Scheme 1).
At the start of this project, we examined the reductive ami-
nation of benzaldehyde with dibenzylamine as a model reac-
tion. Based on the initial optimization, the use of 3 mol% cata-
lyst, a molar ratio of 0.5:0.75 of amine/aldehyde and 50 bar hy-
drogen pressure led to best results (Table 1). The conversion
reported above is related to the conversion of the amine. The
residual carbonyl component is mainly reduced to the corre-
sponding alcohol, which can be easily distilled off in the purifi-
cation procedure. Notably, the choice of solvent has a pro-
nounced effect on the activity of the catalyst. Even though we
have chosen toluene as our solvent, since it gave the best re-
sults under the optimized conditions, we investigated this
effect in more detail. Contrary to previous work on reductions
of nitro compounds,[7a,9] the use of aromatic solvents gave op-
timal results and the desired product is formed in 95% yield.
To demonstrate the general applicability of the catalyst in re-
ductive aminations, various aldehydes and ketones were
tested in reactions with secondary amines (Tables 2 and Figure
1). Gratifyingly, substrates with halogen, hydroxy, ether, and
thioether groups are smoothly hydrogenated (Table 2, en-
tries 3–6 and 13). Moreover, aliphatic aldehydes give moderate
to good yields (Table 2, entries 9, 12, 15). However, lower yield
was obtained for 4-phenylbutanal compared to the simple ali-
phatic aldehyde. This may be attributable to steric hindrance.
Interestingly, both 4’-(methylthio)acetophenone and 2-naph-
thaldehyde gave excellent yields of the corresponding tertiary
amines (Table 2, entries 8 and 13). Using less nucleophilic di-
phenylamine as substrate the respective tertiary amine was ob-
Scheme 1. Direct reductive amination of aldehydes and ketones.
Although organometallic hydrides, for example, borohy-
drides, are established reducing agents for this transformation
on a small scale,[2] in industry catalytic hydrogenation with mo-
lecular hydrogen prevails. Since the first report in 1921, using
a heterogeneous nickel-based catalyst by Mignonac,[3] numer-
ous solid catalysts have been developed for this reaction.
Today, clearly Pd/C is the most commonly used catalytic
system for reductive aminations.[4] Apart from that, supported
[a] S. Pisiewicz, T. Stemmler, Dr. A.-E. Surkus, Dr. K. Junge, Prof. Dr. M. Beller
Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
E-mail: matthias.beller@catalysis.de
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201402527.
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Table 1. Reductive amination of benzaldehyde with dibenzylamine: Varia-
tion of reaction parameters.[a]
Table 2. Reductive amination of aldehydes with diaryl- or dialkylamines.[a]
Entry Product
Yield[b] Entry Product
[%]
Yield[b]
[%]
Entry
Solvent
Conversion[b]
Yield[c]
1
2
THF/H2O[b]
THF
50
70
50
70
3
4
5
6
7
8
9
10
11
toluene
toluene
toluene
toluene
90
90
1
95
10
65
85[d]
40[e]
85[f]
95[g]
85
85[d]
40[e]
85[f]
95[g]
80
toluene
acetonitrile
1,4-dioxane
o-xylene
dibutylether
80
80
80
80
80
80
2
3
4
5
76
57
62
57
11
12
13
14
68
46
80
72
[a] Reaction conditions: 0.5 mmol dibenzylamine, 0.75 mmol benzalde-
hyde, Co3O4/NGr@C (1.5 mol%), 1508C, 15 h, 50 bar H2. [b] THF/H2O 10:1.
[c] Yield determined by GC. Hexadecane as internal standard. [d] Co3O4/
NGr@C (1.5 mol%); CoBr2 was used as the Co-precursor. [e] Co3O4/NGr@C
(1.5 mol%) pyrolized under NH3-atmosphere. [f] Co3O4/NGr@C (1.5 mol%)
was prepared with Vulcan XC72R activated by H2O2. [g] 3 mol% Co3O4/
NGr@C.
tained in yields below 10% (Table 1, entries 16 and 17). In gen-
eral, the reduction of the aldehyde to the corresponding alco-
hol was also observed as a side reaction.
Owing to steric hindrance the application of ketones in the
reductive amination is more challenging. Here, the formation
of the iminium intermediate is disfavored in the equilibrium;
hence elevated temperature and prolonged time are required
for the reaction with ketones (Figure 1). To remove the formed
water and to get complete conversion, molecular sieves (4 ꢁ)
were added. Indeed, the yield increased from <10% to 46%
for the reaction of acetophenone and N-ethylbenzylamine.
With respect to reactivity, for ketones a similar tendency as in
case of aldehydes is observed. Growing steric hindrance and
electrophilicity caused a decrease of the yield. Comparing the
reaction of benzaldehyde and acetophenone with aliphatic dia-
mines significantly lower yield was observed for the ketone. To
our delight, heterocyclic amines tend to give good yields in
this process.
6
65
15
70
7
8
9
62
16
17
<10[d]
69[c]
<10[d]
An important aspect for the practical use of any heterogene-
ous catalyst is the possibility to recycle the material easily.
Thus, we investigated the recycling of our system for the origi-
nal benchmark reaction. As shown in Figure 2, the catalyst was
recycled up to five times with a slight loss of activity (ꢀ10%).
Nevertheless, the yield of the product N,N-dibenzyl-N-ethyl-
amine remained at ꢀ80% after five cycles. Notably, the larger
scale reactions resulted in higher yields (compared to entry 2,
Table 2). This can be explained by some evaporation of the
substrates/products out of the reaction vessel, which on small
scale (0.5 mmol) had a pronounced negative impact.
58[c]
[a] Reaction conditions: 1.5 mmol of amine, 2.25 mmol of aldehyde,
Co3O4/NGr@C (3 mol%), 1508C, 16 h, 50 bar H2 [b] Yields were isolated by
distillation under reduced pressure. [c] Yield in total, deducting all impuri-
ties [d] Detected by GC-MS.
tive reductive amination of aldehydes and ketones. The syn-
thesis of different tertiary amines proceeds in moderate to
good yields without any additives.
In conclusion, we have demonstrated that nanostructured
cobalt oxides represent a general catalytic system for the selec-
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Acknowledgements
The research was funded by the German Federate State
of Mecklenburg-Western Pomerania and the Bundesmi-
nisterium fꢀr Bildung und Forschung (BMBF). The au-
thors thank Dr. W. Baumann, Dr. C. Fischer, S. Buchholz,
S. Schareina, A. Koch, and S. Rossmeisl (all at LIKAT) for
their excellent technical and analytical support.
Keywords: reductive amination · aldehyde · ketone ·
heterogeneous catalysis · cobalt catalyst
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Figure 2. Recycling experiments of model reaction: reductive amination of
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Experimental Section
General procedure for the reductive amination of aldehydes
and ketones: An 8 mL vial containing a stirrer bar was charged
with the respective aldehyde or ketone (1.75 mmol) and dissolved
in dry toluene (3 mL). Then, the amine and carbon-supported
cobalt catalyst (3 mol% Co) was added. In case of ketones addi-
tional molecular sieves (4 ꢁ) are needed. The vials (up to 7) were
placed into a 300 mL autoclave, which was flushed with hydrogen
twice and pressurized to 50 bar hydrogen. It was placed into an
aluminum block, heated up to 1508C or 1608C, and stirred for the
indicated time (16 h/24 h). After the reaction, the autoclave was
cooled to room temperature and depressurized. The catalyst was
filtered off on silica gel and the filtrate was concentrated under re-
duced pressure. The residue was distilled under reduced pressure
to obtain the final product.
Received: July 8, 2014
Revised: July 21, 2014
Published online on && &&, 0000
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S. Pisiewicz, T. Stemmler, A.-E. Surkus,
K. Junge, M. Beller*
&& – &&
Synthesis of Amines by Reductive
Amination of Aldehydes and Ketones
using Co3O4/NGr@C Catalyst
A cobalt from the blue: Heterogenized
cobalt oxide-based catalysts (Co3O4/
NGr@C) allow for reductive aminations
of aldehydes and ketones. Diverse car-
bonyl compounds were transformed
with secondary amines to the corre-
sponding tertiary amines with moderate
to high yields in good selectivity. The
Co3O4/NGr@C catalyst was recycled up
to five times without significant loss of
activity.
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 3
&
4
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These are not the final page numbers!