One-pot reductive amination of carbonyl compounds with nitro compounds over a Ni/NiO composite

Article abstract of DOI:10.1039/d0ra06937j

Easily prepared Ni/NiO acts as a heterogeneous catalyst for the one-pot reductive amination of carbonyl compounds with nitroarenes to afford secondary amines with H₂as a hydride source. This catalytic system does not require a special technique to avoid air-exposure, in contrast to the common heterogeneous Ni catalysts.

Full text of DOI:10.1039/d0ra06937j

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One-pot reductive amination of carbonyl
compounds with nitro compounds over a Ni/NiO
Cite this: RSC Adv., 2020, 10, 32296
composite†
a
a
a
a
Yusuke Kita,
Sayaka Kai, Lesandre Binti Supriadi Rustad, Keigo Kamata
ab
and Michikazu Hara*
Received 30th July 2020
Accepted 19th August 2020
Easily prepared Ni/NiO acts as a heterogeneous catalyst for the one-pot reductive amination of carbonyl
compounds with nitroarenes to afford secondary amines with H as a hydride source. This catalytic
2
DOI: 10.1039/d0ra06937j
system does not require a special technique to avoid air-exposure, in contrast to the common
heterogeneous Ni catalysts.
rsc.li/rsc-advances
15
2
Amines are among the most important organic compounds for Mo have been reported using H as a reductant, severe reac-
the chemical, materials, pharmaceutical and agrochemical tion conditions are typically required (Table S1, ESI†). It is
1
industries. In particular, aromatic and heteroaromatic amines noteworthy that the nitrogen-doped carbon supported cobalt
1
c,2
occupy a privileged position in medicinal chemistry,
as catalysts were reported to be active for one-pot reductive ami-
O as
chlorothiazide, furosemide and acetaminophen. The general a reductant though high temperature was required (Table S2,
exemplied in top-selling drugs such as atorvastatin, hydro- nation using nitroarenes using formic acid or CO/H
2
3
16
methods to prepare aryl and heteroaryl amines are the reductive ESI†).
amination of carbonyl compounds, direct alkylation of amines
with alkyl halides, Buchwald–Hartwig amination and Ullman- using nitro compounds, we have focused on nickel catalysts,
type C–N bond formation. These amination systems utilize which are known as active catalysts for many transformation
4
To develop active catalysts for one-pot reductive amination
5
6
7
17,18
aniline derivatives which are usually prepared in advance by reactions.
The active species is typically metallic nickel,
8
19
hydrogenation of nitroarenes. Direct amine synthesis using which is easily oxidized in air and becomes covered with NiO.
nitroarenes is attractive because it eliminates the hydrogena- Therefore, special techniques to avoid air-exposure (i.e., pre-
tion step, which saves time, energy and cost. Among the ami- reduction in the reaction vessel, glovebox) are required to ach-
nation reactions, reductive amination has been actively ieve high catalytic performance for liquid phase reactions.
investigated due to its high atom economy and ease of indus- Herein we report an easily prepared Ni/NiO composite as
9
trial application (Scheme 1); however, reductive amination has a heterogeneous catalyst for one-pot reductive amination using
frequently been accompanied by unwanted side products due to nitro compounds. This Ni catalyst can be handled under an air
the reduction of carbonyl compounds to alcohols and/or over- atmosphere, even though the supposedly active species,
alkylation of product amines. One-pot reductive amination metallic nickel, is oxidized by air-exposure.
with nitro compounds has been achieved by precious metal
Ni/NiO was prepared by the partial reduction of NiO with H
2
10
ꢀ
catalysis. Recently, precious metal alloy nanoparticles were in the temperature range from 200 to 500 C (Ni/NiO-X: X ¼
demonstrated to exhibit high catalytic performance for one-pot reduction temperature). X-ray diffraction (XRD) patterns of the
reductive amination with nitro compounds, even under mild prepared Ni catalysts aer exposure to air are summarized in
11
ꢀ
reaction conditions. In the context of economic efficiency and Fig. 1(A). When NiO is treated in H at 200 C, the dominant
2
a ubiquitous element strategy, the replacement of precious phase produced is still nickel oxide. Metallic nickel was formed
ꢀ
metals with earth-abundant metals has gained much attention. by reduction at $250 C, which is consistent with the H2-
12
13
14
Although some catalytic systems based on Fe, Cu, Co and
a
Laboratory for Materials and Structures, Institute of Innovative Research, Tokyo
Institute of Technology, Nagatsuta-cho, 4259, Midori-ku, Yokohama 226-8503,
Japan. E-mail: hara.m.ae@m.titech.ac.jp
b
Advanced Low Carbon Technology Research and Development Program (ALCA), Japan
Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi 332-0012, Japan
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/d0ra06937j
1
Scheme 1 One-pot reductive amination using nitroarenes.
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a
Table 2 Catalyst screening
Conv. of 1a
Yield of 3aa
Yield of 4aa
Entry
Catalyst
(%)
(%)
(%)
1
2
3
Ni/NiO-200
Ni/NiO-250
Ni/NiO-300
Ni/NiO-300
Ni/NiO-300
Ni/NiO-350
Ni/NiO-400
Ni/NiO-500
24
22
—
—
77
92
89
62
9
—
12
—
73
25
—
—
—
—
4
5
—
—
2
30
6
51
27
17
33
22
—
—
>99
>99
>99
>99
82
16
>99
36
>99
>99
>99
23
b
4
5
c
6
7
8
9
Ni/Nb
Ni/TiO
Ni/SiO
Ni/ZrO
2
O
5
Fig. 1 (A) XRD patterns for Ni/NiO-X; (a) Ni/NiO-500, (b) Ni/NiO-400, 10
2
(
(
c) Ni/NiO-350, (d) Ni/NiO-300, (e) Ni/NiO-250, and (f) Ni/NiO-200 11
A: Ni, B: NiO), and (B) SEM images of Ni/NiO-300.
12
2
2
d
e
1
1
1
3
4
5
RANEY® Ni
NiO
Ni(OH)
2
20
temperature programmed reduction (H -TPR) prole of NiO in
2
a
Reaction conditions: catalyst (0.05 g), 1a (1 mmol), 2a (1 mmol),
which the H consumption peak begins to increase at around
2
ꢀ
toluene (5 mL), H
determined by GC analysis. 1.2 mmol of 2a and 1 mL of toluene
2
(1 MPa), 80 C, 20 h. Conversion and yield were
ꢀ
20
2
50 C. The ratio of Ni to NiO, determined by Rietveld analysis,
b
c
d
increased with increasing reduction temperature and no peaks were used. Run at 0.5 MPa H
2
pressure for 50 h. Methanol was
e
used as a solvent. Generated by the treatment of RANEY® alloy with
NaOH.
attributed to metallic nickel were evident for Ni/NiO-500
Table 1). The Brunauer–Emmett–Teller (BET) specic surface
area of Ni/NiO was decreased by the reduction treatment with
(Table 1). The decrease of the specic surface areas is due to
(
H
2
the aggregation of Ni particles during reduction, as evidenced
by scanning electron microscopy (SEM) images of Ni/NiO-X
and imine intermediate 4aa were observed in the reaction
mixture by gas chromatography (GC) analysis. The catalytic
activity of the Ni/NiO catalyst was strongly affected by the
reduction temperature during catalyst preparation with Ni/NiO-
(Fig. S3, ESI†) and crystallite diameter estimated from (111)
diffraction lines using Scherrer's equation (Table S3, ESI†).
Fig. 1(C) shows an SEM image of Ni/NiO-300, where the particle
size was estimated to be 0.5–3 mm, and the layered structure of
NiO was maintained aer the reduction treatment (see also
Fig. S4, ESI†).
The one-pot reductive amination of benzaldehyde (2a) with
nitrobenzene (1a) was evaluated with the prepared Ni catalyst
using molecular hydrogen as the reductant (Table 2). In addi-
tion to the desired secondary amine 3aa, aniline, benzyl alcohol
300 showing the highest activity (entry 2). The lack of activity for
Ni/NiO-200 can be rationalized by insufficient reduction, as
evident from the XRD pattern (entry 1). In addition, a low yield
of 3aa was obtained with the catalysts prepared by reduction at
elevated temperatures (entries 6–8). The lower activities of Ni/
NiO-350, -400 and -500 were probably due to smaller amounts
of active sites due to the reduction of the surface area and/or the
aggregation of metallic Ni particles (Tables 1 and S3†). For
comparison of Ni/NiO with simple supported Ni catalysts, one-
pot reductive amination was conducted over Ni catalysts sup-
ported on simple metal oxides of Nb
2
O
5
, TiO
exhibited comparable activity to Ni/NiO
entry 9); however, signicant leaching (3.9%) of the Ni
2 2 2
, SiO and ZrO
Table 1 Specific surface areas and weight ratios of Ni to NiO
(
(
entries 9–12). Ni/SiO
2
b
Weight ratio
(
%)
species was observed in the reaction mixture, as opposed to that
with Ni/NiO-300 (0.1%). Although RANEY® Ni is known to be
Specic surface
a
2
ꢁ1
Entry
Catalyst
area (m g
)
Ni
NiO
21
active for reductive amination, 3aa was obtained only in 22%
yield under the present reaction conditions (entry 13). No
desired product was observed using unreduced NiO and
1
2
3
4
5
6
Ni/NiO-200
Ni/NiO-250
Ni/NiO-300
Ni/NiO-350
Ni/NiO-400
Ni/NiO-500
82
78
41
25
10
<5
—
2
43
66
85
100
100
98
57
34
15
—
22
Ni(OH)
low material balances such as Ni/NiO-400, Ni/Nb
ZrO , we observed benzyl alcohol as a main byproduct, sug-
2
(entries 14 and 15). In the case of the reactions with
2 5
O
and Ni/
2
a
gesting that the hydrogenation of aldehydes is the competitive
side reaction. Because of the high selectivity of Ni/NiO-300, NiO
Specic surface areas were obtained from BET measurements.
Weight ratios were obtained by Rietveld analysis.
b
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support can contribute to suppress the hydrogenation of alde-
hyde. Further optimization was then conducted (Table S2,
ESI†). The yield of 3aa was nally increased to 92% under
higher concentration conditions using 1.5 equivalents of 2a
(entry 4). Reductive amination proceeded even under lower
hydrogen pressure (0.5 MPa), although a longer reaction time
was required (entry 5). The lower loading of Ni/NiO (15 mg) was
accomplished by prolonging the reaction time, affording 3aa in
90% yield (entry 10, Table S4†).
The reusability of Ni/NiO-300 was examined next. The used
Ni/NiO-300 could be recovered from the reaction mixture by
simple ltration, washing with methanol, and drying at 90 C.
Fig. 3 Hydrogenation of 4aa over Ni/NiO and Ni/SiO
2
. Reaction
(1 MPa),
ꢀ
conditions: catalyst (0.05 g), 4aa (1 mmol), toluene (1 mL), H
2
The XRD patterns and the ratio of Ni to NiO were not changed
during one-pot reductive amination (Fig. S2, ESI†). The SEM
images of the recovered catalyst indicates that morphological
changes were negligible (Fig. S6, ESI†). The recovered Ni/NiO
ꢀ
8
0 C.
Ni/NiO for imine hydrogenation is the key for the high activity
on one-pot reductive amination.
Ni/NiO-300 could be applied to the one-pot reductive ami-
nation of other substrates (Table 3). A number of functional
ꢀ
catalyst was reactivated by pre-treatment (150 C, 1 h under
H ow), by which the catalytic activity was maintained at a high
2
rd
level without obvious decline, even aer the 3 reuse (Fig. 2(A)).
A time-course analysis was then conducted under the opti-
mized conditions (Fig. 2(B)). Aniline was generated by the
hydrogenation of nitrobenzene, and imine 4aa was then grad-
ually formed through the dehydrative coupling of 2a with Table 3 Substrate scope
aniline. Hydrogenation of 4aa subsequently afforded the
a
secondary amine 3aa. To determine which step is key for the
one-pot reductive amination, each step was examined using Ni/
NiO-300 and Ni/SiO , respectively. Imine formation step pro-
2
ceeded smoothly even without catalyst (Table S5, ESI†). For the
Isolated yield
of 3 (%)
hydrogenation of 1a, Ni/NiO and Ni/SiO
results (Table S6, ESI†). For the imine hydrogenation step, we
observed the higher activity of Ni/NiO than Ni/SiO (Fig. 3 and
2
gave the comparable
Entry
1
2
2
Table S7†). With these results, the high hydrogenating ability of
b
1
2a
93
c
2
2a
2a
74
88
3
4
2a
82
c
5
1a
1a
62
94
b,c
6
b
7
1a
1a
98
75
d
8
d
e
9
1a
21
Fig. 2 (A) Reuse experiments. Reaction conditions: Ni/NiO-300 (0.05
ꢀ
g), 1a, (1 mmol), 2a, (1.2 mmol), toluene (1 mL), H
2
(1 MPa), 80 C, 20 h.
(
B) Time course of the one-pot reductive amination over Ni/NiO-300.
a
Reaction conditions: Ni/NiO-300 (0.05 g), 1a (1 mmol), 2a (1.2 mmol),
ꢀ ꢀ
2
toluene (1 mL), H (1 MPa), 80 C, 20 h. Run at 100 C. Run for 40 h.
e
b
c
Reaction conditions: Ni/NiO-300 (0.05 g), 1a (1 mmol), 2a (1.2 mmol),
toluene (1 mL), H
ꢀ
d
ꢀ
Run at 120 C for 96 h. NMR yield.
2
(1 MPa), 80 C. (C) Reaction pathway for one-pot
reductive amination over Ni/NiO-300.
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groups, such as ether, ester, chloro and bromo groups proved to Mechanistic studies suggested that Ni(OH)
2
on metallic nickel
be compatible with this catalytic system. The reaction was not can exhibit catalytic activity toward the present one-pot reduc-
sensitive to the steric environment of the nitro group, but was tive amination. These results provide new insights into the
sensitive to that of the formyl group (entries 4 and 8). Electron- development of heterogeneous Ni catalysts.
donating groups retarded the imine hydrogenation step and
thus required higher reaction temperatures (entries 1 and 5).
On the other hand, longer reaction times were necessary for the
Conflicts of interest
electron-withdrawing group on nitrobenzene derivatives due to
the weak nucleophilicity of the aniline intermediates (entry 2).
There are no conicts to declare.
Indeed, imine formation is delayed by electron-withdrawing
group on aniline derivative (Table S5†). The electron- Acknowledgements
withdrawing group on the benzaldehyde derivative retarded
This work was nancially supported by the Advanced Low
reductive amination, although it could facilitate both imine
Carbon Technology Research and Development Program
formation and imine hydrogenation (entry 6). Aliphatic alde-
(
(
ALCA) of the Japan Science and Technology Agency (JST)
JPMJAL1205). A part of this work was supported by the Nagoya
hyde was also applicable though the yield was low due to the
decomposition of aldehyde (entry 9).
The surface of metallic Ni is easily oxidized in air; therefore,
the surface states of Ni/NiO-300 were analysed by X-ray photo-
electron spectroscopy (XPS) and the results are shown in Fig. 3.
In the Ni 2p region of the spectrum for Ni/NiO-300, the main
University microstructural characterization platform as
a program of the “Nanotechnology Platform” of the Ministry of
Education, Culture, Sports, Science and Technology of Japan
(MEXT).
2p3/2 peak is observed at 856.1 eV, which is assignable to
23
Ni(OH)
therefore, hydroxylation of the surface was inevitable. Simi-
larly, NiO and RANEY® Ni were also covered with Ni(OH) aer
2
.
The catalyst was exposed to ambient conditions;
Notes and references
24
2
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boundary region among Ni, NiO and Ni(OH) is considered to
2
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amination with nitro compounds to afford the secondary
amines. No special technique (pre-reduction in the reaction
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