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628
Published on the web December 1, 2012
Carbon Dioxide-promoted Selective Reductive Amination of Aliphatic Ketones
with Aniline and Hydrogen Using a Pt/C Catalyst
Shinichiro Ichikawa, Tsunetake Seki, and Takao Ikariya*
Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology,
2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552
(
Received September 13, 2012; CL-120945; E-mail: tikariya@apc.titech.ac.jp)
Product selectivity in the reductive amination of aliphatic
ketones with aniline and H2 using a 5% Pt/C catalyst was
unsuitable in industrial processes. Although platinum sulfides
are selective heterogeneous catalysts for amination, they are
prepared through complicated procedures and normally exhibit
lower catalytic activities. Therefore, simple, effective, and
environmentally friendly catalytic systems for reductive amina-
tion using molecular hydrogen are highly desired.
improved remarkably in the presence of CO . The CO formed in
2
5
a
situ by the reverse watergas shift reaction selectively poisoned
the Pt sites active for undesired side reactions.
–
H O
2
RHNC(CH3)2
Utilization of carbon dioxide (CO2) as a ubiquitous C1
feedstock as well as an unorthodox reaction medium2,3 is
currently of great importance in organic synthesis. Particularly,
the dense CO2 serves as an efficient green solvent bearing
RNH2
+
RN=C(CH3)2 ð1Þ
H2
1
OH
O
RNH–C(CH3)2
2
,3
physical properties, and can often affect the outcome of
catalytic reactions in a number of ways. Eckert and co-workers,
for example, have demonstrated the advantage of the use of
alkylcarbonic acids (ACAs) generated in situ in CO2-expanded
alcohols for acid-promoted catalytic reactions.4 Since the
strength of the ACAs is readily tunable through adjustment of
the CO2 pressures, the outcome of the catalytic reactions can be
controlled by changing the CO2 pressures. The ACAs formed
in situ can be separated easily after the reaction by simple
depressurization, and are possible alternatives to the problematic
solid or liquid acid catalysts with their inherent toxicity and
corrosivity.
In a previous paper, we demonstrated the advantage of the
use of CO2 under its supercritical condition for the selective
hydrogenation of halogenated nitrobenzenes to the correspond-
ing anilines over a solid catalyst, in which the CO formed in situ
via the reverse watergas shift reaction served as a selective
We first examined the effect of the CO pressure on the
2
outcome of the reductive amination of the acetone (2) with the
aniline (1) over a conventional 5% Pt/C catalyst using H2. As
shown in Table 1, in the absence of CO2, the reaction under
2.5 MPa H at 60 °C gave the desired product, N-isopropylani-
2
line (3), and its intermediate, N-isopropylideneaniline (4) in
35.2% yield, along with the undesired over-reduction products,
N-isopropylcyclohexylamine (5) and 2-propanol (6) after reac-
tion for 2.5 h, in 36.3% conversion (Entry 1). This result
indicates that the Pt/C catalyst without any modification
promotes the hydrogenation of the benzene ring and the
carbonyl group of acetone, resulting in a decrease in the product
selectivity.
Notably, the addition of pressurized CO up to 3.0 MPa
2
could completely suppress by-product formation without de-
creasing the yield of the target compound 3 (Entry 4). A further
modifier to suppress the undesired side reactions in the hydro-
3
genation. This surface modification using pressurized CO is
Table 1. Reductive amination of acetone with aniline and H2
over the 5% Pt/C catalyst: Effect of the addition of CO2a
2
attractive owing to its simplicity and tunable features, and offers
advantages over classical methods using catalysts modified with
some toxic additives. Herein, we disclose the positive effect of
CO2 addition on the catalytic reductive amination of aliphatic
ketones with aromatic amines using the precious metal catalyst,
Pt/C, under a H atmosphere. The product selectivity in the
amination was improved markedly by the addition of CO2 as a
catalyst modifier.
The reductive amination of carbonyl compounds, which is
one of the most practical industrial processes for accessing
amine compounds, proceeds in consecutive steps including the
condensation of amines and carbonyls, the dehydration of the
resulting amino alcohols, and the reduction of imines. Over the
last few decades, many homogeneous and heterogeneous
catalytic systems have been developed to improve the reactivity
and selectivity of reductive aminations. Of these, the heteroge-
neously catalyzed reductive amination of carbonyl compounds
with molecular hydrogen may be the most ideal industrial
process, because the use of the expensive and environmentally
NH2
5 % Pt/C
+
+
H2
N
O
CO2
1
:2
1
2
2
NH
NH
+
+
+
OH
3
4
5
6
P, CO2 Conv.
Yield/%
Entry
/MPa
/%
3
4
5
6
1
2
3
4
5
0
36.3
37.7
44.6
41.2
32.2
27.3
33.6
34.1
37.5
33.0
24.9
16.7
1.6
3.3
6.7
7.8
7.2
9.9
1.1
0.2
9.0
0.6
0.5
1.0
3.0
5.0
10.0
<0.1 <0.1
nd
nd
nd
nd
nd
nd
6
a
Aniline 5.0 mmol, acetone 10 mmol, 5% Pt/C 10 mg, PH
2
57
b
problematic NaBH4 or NaBH3CN as reducing agents
is
2.5 MPa, 60 °C, 150 min. Not detected.
Chem. Lett. 2012, 41, 16281629
© 2012 The Chemical Society of Japan
Ichikawa, Shinichiro
