Heterogeneous Ni catalysts for N-alkylation of amines with alcohols

Article abstract of DOI:10.1021/cs4001267

Nickel nanoparticles loaded onto various supports (Ni/MO_x) have been prepared and studied for the N-alkylation of amines with alcohols. Among the catalysts, Ni/θ-Al₂O₃ prepared by in situ H ₂-reduction of NiO/θ-Al₂O₃ shows the highest activity, and it acts as reusable heterogeneous catalyst for the alkylation of anilines and aliphatic amines with various alcohols (benzyl and aliphatic alcohols) under additive free conditions. Primary amines are converted into secondary amines and secondary amines into tertiary amines. For the reaction of aniline with an aliphatic alcohol the catalyst shows higher turnover number (TON) than precious metal-based state-of-the-art catalysts. Mechanistic studies suggest that the reaction proceeds through a hydrogen-borrowing mechanism. The activity of Ni catalysts depends on the nature of support materials; acid-base bifunctional supports give higher activity than basic or acidic supports, indicating that acid-base sites on supports are necessary. The presence of basic (pyridine) or acidic (acetic acid) additive in the solution decreased the activity of Ni/θ-Al₂O₃, which suggests the cooperation of the acid-base site of θ-Al₂O₃. For a series of Ni/θ-Al₂O₃ catalysts with different particle size, the turnover frequency (TOF) per surface Ni increases with decreasing Ni mean particle size, indicating that low-coordinated Ni species and/or metal-support interface are active sites. From these results, we propose that the active site for this reaction is metal-support interface, where low-coordinated Ni⁰ atoms are adjacent to the acid-base sites of alumina.

Full text of DOI:10.1021/cs4001267

Research Article
pubs.acs.org/acscatalysis
Heterogeneous Ni Catalysts for N‑Alkylation of Amines with Alcohols
Ken-ichi Shimizu,*,†,‡ Naomichi Imaiida,§ Kenichi Kon,† S. M. A. Hakim Siddiki,‡ and Atsushi Satsuma‡,§
†Catalysis Research Center, Hokkaido University, N-21, W-10, Sapporo 001-0021, Japan
‡Elements Strategy Initiative for Catalysts and Batteries, Kyoto University, Katsura, Kyoto 615-8520, Japan
§Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan
S
* Supporting Information
ABSTRACT: Nickel nanoparticles loaded onto various supports (Ni/
MOx) have been prepared and studied for the N-alkylation of amines with
alcohols. Among the catalysts, Ni/θ-Al2O3 prepared by in situ H2-
reduction of NiO/θ-Al2O3 shows the highest activity, and it acts as
reusable heterogeneous catalyst for the alkylation of anilines and aliphatic amines with various alcohols (benzyl and aliphatic
alcohols) under additive free conditions. Primary amines are converted into secondary amines and secondary amines into tertiary
amines. For the reaction of aniline with an aliphatic alcohol the catalyst shows higher turnover number (TON) than precious
metal-based state-of-the-art catalysts. Mechanistic studies suggest that the reaction proceeds through a hydrogen-borrowing
mechanism. The activity of Ni catalysts depends on the nature of support materials; acid−base bifunctional supports give higher
activity than basic or acidic supports, indicating that acid−base sites on supports are necessary. The presence of basic (pyridine)
or acidic (acetic acid) additive in the solution decreased the activity of Ni/θ-Al2O3, which suggests the cooperation of the acid−
base site of θ-Al2O3. For a series of Ni/θ-Al2O3 catalysts with different particle size, the turnover frequency (TOF) per surface Ni
increases with decreasing Ni mean particle size, indicating that low-coordinated Ni species and/or metal−support interface are
active sites. From these results, we propose that the active site for this reaction is metal−support interface, where low-coordinated
Ni0 atoms are adjacent to the acid−base sites of alumina.
KEYWORDS: alcohols, amines, heterogeneous catalysis, nickel, nanoparticles
accepted mechanism of this type of reaction, a so-called
borrowing-hydrogen3 (or hydrogen-autotransfer4) method-
ology, involves dehydrogenation of alcohols to provide
carbonyl compounds, which are converted to imines, and the
subsequent reduction of imines by the transition metal hydrides
formed in the first step, yielding higher order amines. Recently,
homogeneous Ru8,9 and Ir10−13 catalysts were shown to be
highly effective for this one-pot reaction, but these systems have
problems such as difficulty in the recovery and reuse of
expensive catalysts and the use of cocatalysts such as base and
stabilizing ligand. Recyclable heterogeneous noble metal
catalysts (Pd,14−16 Ru,17−19 Ag,20−22 Au,23 and Pt24) have
been also reported, but some of them suffer from high catalyst
loading,17−21 low selectivity to monoalkylation, and needs of
high pressure (5 atm of N2),23 H2 atmosphere,14 high
temperature,15 or cocatalysts.20,21 From the environmental
and economic viewpoints, it is desired to accomplish this
reaction by an inexpensive catalyst. Non-noble metal
1. INTRODUCTION
In view of sustainable chemistry, discovery of atom-efficient
chemical transformations that minimize byproducts and
separation of waste and eliminate precious metals is one of
the most important goals in catalysis research. Nickel (Ni) as a
cheap element is an ideal candidate if comparable activities and
selectivities can be achieved. Despite the fact that Ni-containing
solids, such as sponge Ni (Raney Ni), have been used as a
promoter or heterogeneous catalyst for hydrogenation of
various compounds, advances in the field of heterogeneous
non-noble metal catalyzed organic synthesis is still in its
infancy. Recently, Yus and co-workers1 have demonstrated that
stoichiometric or substoichiometric amounts (20−100 mol %)
of Ni nanoparticles (NPs) promote various types of hydrogen
transfer reactions which are typically implemented by noble
metal-based catalysts. Our ongoing interest in the supported
metal NP catalysis for dehydrogenation/hydrogenation reac-
tions2 combined with the pioneering study by Yus et al.1
motivated us to investigate possibilities of supported Ni NPs as
cheaper alternatives to the well established noble metal catalysts
in a hydrogen transfer reaction.
25
homogeneous catalysts, such as Cu(OAc)2 and FeBr3,26
were developed, but they needed basic cocatalyst (t-BuOK),25
ligand (amino acid),26 or high temperatures (160−200 °C).26
Heterogeneous Fe,27,28 Cu,4,29−35 and Ni4,36,37 catalysts
generally suffer from low turnover number (TON), limited
scope, and needs of high temperatures, high catalyst loading, H2
N-Alkyl amines are important building blocks used in the
synthesis of a wide range of pharmaceuticals, agrochemicals,
surfactants, and bioactive molecules. The alkylation of amines
with alcohols to give higher order amines3−37 is an attractive
and environmentally friendly alternative to the conventional
methods, such as alkylation of amines with alkyl halides or
reductive amination of carbonyl compounds. A generally
Received: February 18, 2013
Revised: March 19, 2013
© XXXX American Chemical Society
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a
Table 1. N-Alkylation of Aniline with 1-Octanol by Various Catalysts
yield (%)
entry
catalyst
conv of 1a (%)
3a
4a
b
1
NiO/θ-Al2O3
Ni/θ-Al2O3
Ni/θ-Al2O3-air
Ni/α-Al2O3
Ni/γ-Al2O3
Cu/γ-Al2O3
Co/γ-Al2O3
Ir/γ-Al2O3
Re/γ-Al2O3
Au/γ-Al2O3
Ru/γ-Al2O3
Rh/γ-Al2O3
Ag/γ-Al2O3
Pd/γ-Al2O3
θ-Al2O3
1
99
8
0
99
7
0
0
1
1
4
4
6
0
0
1
1
1
1
0
0
0
5
0
0
2
3
3
3
1
0
0
2
2
c
3
4
3
1
5
60
24
8
60
20
2
6
7
8
37
0
35
0
9
10
11
12
13
14
0
0
2
1
3
2
1
0
2
0
d
15
0
0
e
16
Ni powder
Raney Ni
0
0
e
17
19
0
11
0
18
19
20
21
22
23
24
25
26
27
Ni/CaO
Ni/MgO
0
0
Ni/La2O3
Ni/Y2O3
3
0
11
8
7
Ni/CeO2
5
Ni/ZrO2
11
9
8
Ni/TiO2
6
Ni/Nb2O5
Ni/SnO2
1
0
0
0
Ni/SiO2
5
2
a
b
c
Conversion of 1a and yields of 2a and 3a were determined by GC based on 1a. Catalysts were not prereduced. Prereduced Ni/θ-Al2O3 was
d
e
exposed to air at room temperature for 0.5 h. θ-Al2O3 = 0.1 g. Ni = 5 mol %.
atmosphere, or stoichiometric amount of basic cocatalyst. For
example, Ni/Cu coloaded Al2O3 catalyst recently reported by
Sun et al. exhibited a TON of 1.9 for N-alkylation of aniline
with benzyl alcohol in the presence of 25 mol % NaOH and
12.5 mol % CaCl2.37 In the course of our recent findings on the
direct amination of alcohols with NH3 by Ni nanoparticle-
loaded θ-Al2O3 (Ni/θ-Al2O3),38 we have discovered that Ni/θ-
Al2O3 acts as an effective and recyclable heterogeneous catalyst
for the title reaction. To the best of our knowledge, this is the
first versatile synthesis of amines from Ni-catalyzed N-
alkylation of various amines with aliphatic and aromatic
alcohols without any additives under relatively mild conditions.
standard at ambient temperature on a JEOL JNM-ECX 400
operating at 400 MHz.
2.2. Catalyst Preparation. γ-Al2O3 (with surface area of
124 m2 g−1), θ-Al2O3 (112 m2 g−1), and α-Al2O3 (17 m2 g−1)
were prepared by calcination of γ-AlOOH (Catapal B Alumina
purchased from Sasol) for 3 h at 900, 1000, and 1200 °C,
respectively. MgO (JRC-MGO-3, 19 m2 g−1), TiO2 (JRC-TIO-
4, 50 m2 g−1), and CeO2 (JRC-CEO-3, 81.4 m2 g−1) were
supplied from Catalysis Society of Japan. Hydroxides of Zr, Sn,
Y, and La were prepared by hydrolysis of zirconium oxynitrate
2-hydrate, SnCl4·6H2O, or metal nitrates in distilled water by
gradually adding an aqueous NH4OH solution (1.0 mol dm−3),
followed by filtration of precipitate, washing with distilled water
three times, and drying at 100 °C for 12 h. Ca(OH)2 and
Nb2O5·nH2O (supplied by CBMM) were commercially
supplied. CaO, Y2O3, La2O3, ZrO2, Nb2O5, and SnO2 were
prepared by calcination of these hydroxides at 500 °C for 3 h.
NiO/θ-Al2O3 (Ni loading = 5 wt %) was prepared by an
impregnation method: a mixture of θ-Al2O3 (18 g) and an
aqueous solution of Ni(NO3)2·6H2O (0.162 M, 100 cm3) was
evaporated at 50 °C, followed by drying at 90 °C for 12 h and
calcination in air at 300 °C for 1 h. Before each catalytic
2. EXPERIMENTAL SECTION
2.1. General. Commercially available organic compounds
(from Tokyo Chemical Industry or Kishida Chemical) were
used without further purification. The GC (Shimadzu GC-14B)
and GCMS (Shimadzu GCMS-QP2010) analyses were carried
out with Ultra ALLOY capillary column UA+-5 (Frontier
1
Laboratories Ltd.) using nitrogen as the carrier gas. H NMR
spectra were recorded in CDCl3 with TMS as an internal
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experiment, Ni/θ-Al2O3 was prepared by in situ prereduction of
NiO/θ-Al2O3 in a glass (Pyrex or quartz) tube under a flow of
H2 (20 cm3 min−1) at a reduction temperature (TH2) of 500 °C
for 0.5 h. Ni/θ-Al2O3 with different Ni loading (5 and 20 wt
%), 5 wt % Ni loaded on various supports (α-Al2O3, La2O3,
Y2O3, CeO2, ZrO2, TiO2, Nb2O5, SnO2), was prepared by the
impregnation method in the same manner as the preparation of
Ni/θ-Al2O3 (Ni loading = 10 wt %). CaO and MgO-supported
Ni (5 wt %) were prepared by the impregnation method,
followed by drying at 90 °C for 12 h, and by in situ
prereduction of the precursor under H2 at 500 °C. γ-Al2O3-
supported metal catalysts, M/γ-Al2O3 (M = Ni, Co, Cu, Ru, Pd,
Rh, Ag, Ir, Re), with metal loading of 5 wt % were prepared by
impregnation method in a similar manner as the preparation of
Ni/θ-Al2O3 using aqueous solution of metal nitrates (for Ni,
Co, Cu), IrCl3·nH2O, RuCl3, NH4ReO4, or aqueous HNO3
solution of Rh(NO3)3 or Pd(NO3)2. Au/γ-Al2O3 (Au = 1 wt %)
was prepared by the deposition−precipitation method with
HAuCl4. Raney Ni (B113W, Ni >90%) was supplied from
Evonik Industries. Ni powder was purchased from Mitsuwa
Chemical.
reaction. To optimize the metal content in Ni/θ-Al2O3, the
catalysts with different Ni content (5, 10, 20, 50 wt %) were
tested under reflux conditions. The initial formation rate of 3a
(V0), measured under the condition where the conversion of 1a
was below 30%, is listed in Table 2. It is found that the metal
Table 2. Preparation Conditions, Ni Particle Size, and
Catalytic Activity of Ni/θ-Al2O3 Catalysts
a
b
c
d
e
Ni loading (wt
%)
TH2
°C
/
D /
DV
/
V0 /mol molNi
TOF /
nm
nm
h−1
h−1
5
10
20
50
50
500
500
500
500
800
6.1
6.5
7.6
9.0
48
35
16
2.0
1.0
314
267
130
23
8.8
9.6
12.2
15.6
13.5
16.3
14
a
b
Temperatures of prereduction in H2. Mean diameter of Ni particles
c
estimated by TEM. Volume−area mean diameter of Ni particles
d
estimated by TEM. Initial formation rate of 3a per total Ni atoms
e
(mol of 3a molNi h−1). TOF per surface Ni atoms calculated from V0
and DV.
2.3. Characterization. Transmission electron microscopy
(TEM) measurements were carried out by using a JEOL JEM-
2100F TEM operated at 200 kV. X-ray diffraction (XRD)
patterns of the powdered catalysts were recorded with a Rigaku
MiniFlex II/AP diffractometer with Cu Kα radiation.
content of 5 wt % gives the highest activity. The effect of the
prereduction temperature (300−800 °C) of 5 wt % Ni/θ-Al2O3
showed that the catalyst reduced at 500 °C gave the highest
activity (result not shown).
2.4. Typical Procedures of Catalytic Reactions. After
the prereduction under a flow of H2 at 500 °C for 0.5 h, we
carried out catalytic tests without exposing the catalyst to air as
follows. The mixture of o-xylene (1.5 mL), alcohol (1.2 mmol),
and amine (1.0 mmol) was injected to the prereduced catalyst
inside a reactor (cylindrical glass tube) through a septum inlet,
followed by filling with N2. Then, the resulting mixture was
stirred under reflux; bath temperature was 155 °C, and reaction
temperature was ca. 144 °C. Conversion and yields of products
were determined by GC using n-dodecane as an internal
standard. The products were identified by H NMR as well as by
GC−MS equipped with the same column as GC and by
comparison with commercially pure products.
3.2. Catalytic Performance of Ni/θ-Al2O3. The catalyst
optimization results show that the Ni/θ-Al2O3 catalyst with Ni
loading of 5 wt % prereduced at 500 °C is the best catalyst.
With this catalyst, we studied the reusability and the scope of
the present system with regard to various combinations of
amines (1.0 mmol) and alcohols (1.2 mmol) in o-xylene under
reflux in 1 atm of N2. First, we studied a leaching test and the
catalyst reusability using the reaction of 1a with benzyl alcohol
by Ni/θ-Al2O3 (1 mol % Ni with respect to 1a) as a model
reaction. As shown in Table 3 (entry 1), the N-alkylation of 1a
with benzyl alcohol 2b for 3 h resulted in full conversion of 1a
and 99% yield of the N-alkylated amine 3b, corresponding to
the TOF of 33 h−1 based on the total amount of Ni. Byproducts
such as tertiary amine and unreduced byproduct (imine) were
not observed. The reaction was completely terminated by a
removal of Ni/θ-Al2O3 from the reaction mixture at 35% yield
of 3b (t = 0.5 h), and further heating of the filtrate under reflux
conditions did not increase the product yield. ICP analysis of
the filtrate confirmed that the content of Ni in the solution was
below the detection limit. These results confirm that the
reaction is attributed to the heterogeneous catalysis of Ni/θ-
Al2O3. After the reaction for 3 h, the catalyst was separated
from the reaction mixture by a centrifugation. The recovered
catalyst was washed with acetone and water, followed by
calcination in air at 300 °C for 0.5 h, and by reducing in H2 at
500 °C for 0.5 h. As shown in Table 3 (entry 1), the recovered
catalyst was reused at least three times without any indication
of catalyst deactivation.
3. RESULTS AND DISCUSSION
3.1. Catalyst Optimization. We studied the influence of
various catalyst parameters on the catalytic activity for N-
alkylation of aniline 1a with 1-octanol 2a to yield the mono N-
alkylated amine product 3a in o-xylene under reflux by 1 mol %
of the catalyst for 3 h (Table 1). First, various metal (M)-
loaded γ-Al2O3 catalysts (M = Ni, Cu, Co, Ir, Re, Au, Ru, Rh,
Ag, Pd), prereduced at 500 °C, were studied in the reaction of
1a with 2a (entries 5−14). It was found that Ni/γ-Al2O3
showed the highest yield of 3a. Next, we carried out catalytic
tests for commercial Ni compounds and a series of metal oxide
(MOx)-supported Ni catalysts with the same loading (5 wt %).
Alumina supports with different crystal phase were also tested
as a support of Ni (entries 2, 4, 5). The alumina with spinel
structure (θ-Al2O3 and γ-Al2O3) gave higher yields than that
with corundum structure (α-Al2O3), and θ-Al2O3 gave the
highest yield (99%). Among various metal oxides as support
materials (entries 2, 18−27), Ni/θ-Al2O3 showed the highest
yield of 3a. Use of large amount of a conventional Ni catalyst (5
mol % of Raney Ni or Ni powder, entries 16, 17) resulted in
lower yield of 3a than Ni/θ-Al2O3. NiO-loaded θ-Al2O3 (NiO/
θ-Al2O3) and θ-Al2O3 were completely inactive, indicating that
nickel oxide and the support itself could not catalyze the
The scope of the reactions of aniline 1a with various alcohols
was conducted using Ni/θ-Al2O3 (1 mol %) as listed in Table 3.
In the literature, the alkylation of anilines with aliphatic alcohols
has been unsuccessful in some catalytic systems possibly
because of the low nucleophilicity of anilines than aliphatic
amines as well as low reactivity of aliphatic alcohol. Recent
successful examples for the alkylation of aniline with aliphatic
alcohols are listed in Table S1 in the Supporting Information.
In our catalytic system, the reactions of aliphatic primary
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a
Table 3. N-Alkylation of Aniline with Various Primary and Secondary Alcohols
a
b
c
d
Ni/θ-Al2O3 (Ni content = 5 wt %). Conversion and yields were determined by GC based on aniline. Isolated yield. First reuse. Second reuse.
e
f
g
h
i
Third reuse. T = 130 °C. 20 mmol of EtOH, no solvent, reflux (78 °C). Cat. = 2 mol %. 3 mmol of 2-propanol.
alcohols with aniline resulted in selective monoalkylation in
high yields (entries 5−8). The TOF value of 33 h−1 for the Ni/
θ-Al2O3 catalyst is larger than those of the previously reported
excellent catalytic systems using homogeneous and heteroge-
neous noble metal catalysts (Table S1 in the Supporting
Information): 2.9 h−1 for Cp*Ir complex (with basic
cocatalyst),10 0.6 h−1 for Ru(OH)x/Al2O3,17 2.0 h−1 for Au/
TiO2,23 15 h−1 for Pt-Sn/Al2O3,24 and 3.6 h−1 Cu-Ag/γ-
Al2O3.22 The reaction of 1a with 2a with 0.1 mol % of the Ni/
θ-Al2O3 catalyst for 120 h led to 80% yield of 3a, corresponding
to a TON of 800 (eq 1). This value is also larger than those of
(81−94%). To the best of our knowledge, our result represents
the first successful example of N-alkylation of aniline with
various aliphatic alcohols using a Ni-based catalyst without any
additives. The reactions of aniline with electron-rich benzyl
alcohols also proceeded in good yield (entries 2−4).
Table 4 shows the results of N-alkylation of various amines
with benzyl alcohol. The reactions of substituted anilines,
including a sterically hindered one (entry 1), proceeded in
excellent yields (entries 1−5). Aliphatic primary amines
(entries 6, 7) and a cyclic secondary amine (entry 8) were
also tolerated. The TON of 42 for the reaction of n-octylamine
with benzyl alcohol is larger than that of a recently reported
heterogeneous non-noble metal catalyst: TON of 11 for
Cu(OH)x/Al2O3.35
As shown in Table 5, challenging reactions of primary and
secondary amines with aliphatic primary alcohols were also
successful using 2 mol % Ni/θ-Al2O3 to give the corresponding
secondary and tertiary amines in good yield (87−93%). In the
literature, the reaction of aliphatic alcohol with aliphatic amines
by heterogeneous catalysts is rare. One example is the recent
report by He et al., in which Au/TiO2 (5 mol %)23 shows a
moderate yield (53%) for the reaction of the cyclohexylamine
with n-decanol after a long reaction time (55 h), corresponding
to TOF of 0.2 h−1. Ni/θ-Al2O3 shows higher yield (88%) and 9
times higher TOF (1.8 h−1) for this reaction (entry 4) than Au/
the previous state-of-the-art catalysts (Table S1 in the
Supporting Information). The secondary aliphatic alcohols
(entries 9−11) were tolerated with good to excellent yields
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a
Table 4. N-Alkylation of Various Amine with Benzyl Alcohols
a
b
c
Ni/θ-Al2O3 (Ni content = 5 wt %). Yields were determined by GC based on amine. Isolated yield. Amine (0.5 mmol), alcohol (2.0 mmol), cat. =
d
2 mol %, T = 135 °C. Cat. = 2 mol %.
a
Table 5. N-Alkylation of Various Amines with Primary Alcohols
a
b
c
Ni/θ-Al2O3 (Ni content = 5 wt %). Yields were determined by GC based on amine. Amine (1.0 mmol), alcohol (1.0 mmol). Amine (1.0 mmol),
alcohol (2.0 mol), T = 130 °C.
TiO2. From the above results, it is shown that the present Ni/θ-
Al2O3-catalyzed system is a highly active, versatile and cost-
effective method for the direct synthesis of secondary and
tertiary amines.
3.3. Structure−Activity Relationship. First, we discuss
the role of the support in the Ni-catalyzed alkylation of aniline.
As listed in Table 1, we tested a series of metal oxide-supported
Ni catalysts with the same Ni content (5 wt %). Basic (MgO,
CaO), amphoteric (Al2O3, Y2O3, La2O3, CeO2, ZrO2), and
relatively acidic (TiO2, Nb2O5, SnO2) supports were selected
according to well-known classifications of acid−base character
of metal oxides.39 The initial reaction rates for N-alkylation of
aniline with 1-octanol or benzyl alcohol are plotted in Figure 1
as a function of the electronegativity of the support metal oxide,
which is generally used as a parameter of acidity of metal
oxides.2,38,40 The electronegativity of metal oxide is calculated
according to the concept of Sanderson based on the
electronegativity of the element.38 There is a general tendency
that a volcano-type relationship exists between the catalytic
activity and acidity of the support. Among the supports with
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3), prepared by exposing the as-reduced Ni/θ-Al2O3 catalyst to
the ambient conditions for 0.5 h, showed no activity. This
suggests that the metallic Ni0 species on the surface of Ni
nanoparticles are the active species and reoxidation of them by
air results in the catalyst deactivation. Inert nature of NiO
species was also confirmed by the fact that NiO/θ-Al2O3 did
not catalyze the reaction (Table 1, entry 1). To discuss the
effect of Ni metal particle size, a series of Ni/θ-Al2O3 catalysts
with different particle size were prepared by changing the Ni
loading and reduction temperature, and the initial rates for the
reaction of aniline with 1-octanol or benzyl alcohol were
determined (Table 2). XRD patterns of these Ni/θ-Al2O3
catalysts are shown in Figure S1 in the Supporting Information.
A sharp line at 44.50° due to Ni metal was observed in the
XRD pattern of the high Ni loading (20, 50 wt %) catalysts. A
significantly broad and weak line due to Ni metal was observed
in the patterns of the 5 and 10 wt % Ni catalysts. Transmission
electron microscopy (TEM) analysis of Ni/θ-Al2O3 catalysts
(Ni = 5, 10, 20, 50 wt %) showed spherical or semispherical Ni
particles. The particle size distribution for each catalyst is
shown in Figure S1 in the Supporting Information. It is known
that the mean particle diameter estimated from the number of
surface atoms on the assumption of spherical particles agrees
with a volume−area mean diameter measured by TEM.42 As
shown in Table 2, a series of Ni/θ-Al2O3 catalysts with different
volume−area mean diameter (7.6−16.3 nm) were prepared.
According to the established method, the number of the surface
Ni atoms was estimated using the mean Ni particle size
according to the established method.43 Using the number of the
surface Ni atoms and the initial rates, the TOF per surface Ni
atom was estimated (Table 2). As shown in Figure 3, TOF
○
▼
)
Figure 1. Rate of N-alkylation of aniline with ( ) 1-octanol or (
benzyl alcohol by Ni/θ-Al2O3 at 144 °C as a function of the
electronegativity of support metal oxide.
basic to amphoteric nature (CaO ∼ Al2O3), the activity
increases with the electronegativity (acidity) of the support
oxide, and acidic support shows lower activity than amphoteric
supports. These results suggest that both acidic and basic sites
on θ-Al2O3 are necessary for this reaction. In our recent report,
densities of surface acidic and basic site on each catalyst were
estimated based on the surface area of the catalyst and the
number of desorbed NH3 and CO2 during NH3- and CO2-
temperature programmed desorption experiments and were
adopted as experimental indexes of the acid−basicity of the
catalyst.38 For the supports with basic to amphoteric nature
(CaO ∼ Al2O3), the increase in the electronegativity generally
resulted in a decrease in the density of the basic sites and
increase in the acid site density.38 The supports with high
electronegativity (SnO2) had almost no basic site. Comparing
the activity and the acid−base character of the catalyst, we can
conclude that the copresence of acidic and basic sites on the
surface of support oxides is indispensable for this reaction. To
further verify this hypothesis, we studied the poisoning effects
of acidic or basic additives in the reaction mixture on the
activity of Ni/θ-Al2O3 for the reaction of aniline with 1-octanol.
As shown in Figure 2, the reaction rate was decreased by
Figure 3. TOF per surface Ni atom for N-alkylation of aniline with
○
▼
( ) 1-octanol or ( ) benzyl alcohol by Ni/θ-Al2O3 at 144 °C as a
function of mean Ni particle size (from Table 2).
decreases with the mean diameter of Ni particles. It is well-
known that fraction of surface metal atoms at low-coordinated
sites as well as that of metal/support perimeter sites with
respect to all the surface metal atoms decreases with the particle
size. Taking into account the above-mentioned suggestion that
the acid−base sites of alumina are indispensable for this
reaction, the result in Figure 3 suggests that the active site for
the reaction can be metal/support interface, where low-
coordinated Ni0 atoms are adjacent to the acid−base sites of
alumina.
3.4. Reaction Scheme. In analogy to previously reported
catalytic systems, the present Ni-catalyzed N-alkylation may
proceed through a sequential reaction pathway (the hydrogen-
borrowing pathway) in which three elementary steps (alcohol
dehydrogenation, imine formation, and hydrogenation) are
○
Figure 2. Rate of N-alkylation of aniline with ( ) 1-octanol by Ni/θ-
Al2O3 at 144 °C as a function of the concentration of pyridine and
acetic acid.
catalytic amount of acidic (acetic acid) and basic (pyridine)
additives. It is established that the reaction of acetic acid with
Al2O3 results in the formation of the acetate ion in the acid−
base pair site (Alδ+−Oδ− site),41 while pyridine adsorbs on the
surface Lewis acid site (exposed Al cation) of Al2O3.39
Therefore, the result of the poisoning experiment indicates
that the acid−base pair site and the surface Lewis acid site are
necessary for this reaction.
Next, we discuss the effect of Ni structure on the catalytic
activity. The catalyst named Ni/θ-Al2O3-air in Table 1 (entry
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Research Article
involved.3−5 Our recent results44 showed that Ni/θ-Al2O3 was
active for the acceptor-free dehydrogenation of alcohols to the
corresponding carbonyl compound. Thus, the initial stage of
the reaction would be the dehydrogenation of alcohol to a
carbonyl intermediate. We studied kinetic experiments for the
N-alkylation of aniline with benzyl alcohol by Ni/θ-Al2O3. The
time course of the reaction (Figure 4) showed a profile
Figure 5. Formation rate of 3b at 120 °C as a function of the
concentration of aniline (Caniline = 0.16 to 1.50 M) and benzyl alcohol
(CBnOH = 0.13 to 1.27 M).
the benzyl alcohol concentration showed a relatively large
positive-order dependence (n = 0.41). These results suggest
that benzyl alcohol is involved in a relatively slow step but
aniline is not involved in a kinetically significant step. Based on
the above results, a plausible mechanism is given in Scheme 1.
▽
○
Figure 4. Yields of unreacted aniline ( ), amine 3b ( ), and imine 4b
Scheme 1. A Plausible Mechanism of Ni/Al2O3-Catalyzed N-
Alkylation of Amines with Alcohols
●
▼
( ) for N-alkylation of aniline 1a with ( ) benzyl alcohol by Ni/θ-
Al2O3 (1 mol %) at 140 °C.
characteristic of a consecutive reaction mechanism: the imine
intermediate 4b, formed at an initial induction period, was
consumed after 3 h to give the hydrogenated product 3b. In the
absence of the catalyst, the reaction of benzaldehyde with
aniline yielded a quantitative amount of 4b at room
temperature (not shown), indicating that the imine formation
was very fast. In the presence of Ni/θ-Al2O3, no hydrogenation
of the imine 4b under H2 (1 atm) occurred (eq 2), whereas the
The reaction begins with the dehydrogenation of alcohol by Ni
sites to a carbonyl compound, which reacts with amine to give
an imine. Finally, hydrogen transfer from Ni−H species to the
imine gives N-alkylated amine. The dehydrogenation step could
be a relatively slow step. Taking into account the proposed
model of active sites, low-coordinated Ni0 sites on small Ni
metal NPs could be responsible for the dehydrogenation and
hydrogen transfer steps. Support-specific catalysis observed in
this study may be explained by assuming that the acid−base
pair site of Al2O3 adjacent to the Ni0 sites assists important
steps such as deprotonation of alcohol and hydrogen transfer
step. Mechanistic studies are ongoing to clarify the role of the
support in the catalytic cycle.
transfer hydrogenation of the imine 4b (1 mmol in o-xylene) by
2 equiv of benzyl alcohol with Ni/θ-Al2O3 gave a quantitative
yield of the hydrogenated product 3b and benzaldehyde (eq 3).
4. CONCLUSIONS
We have demonstrated a versatile synthesis of amines from Ni-
catalyzed N-alkylation of amines with aliphatic and aromatic
alcohols by θ-Al2O3-supported Ni metal NPs (Ni/θ-Al2O3),
prepared by in situ H2-reduction of NiO/Al2O3. This method
provides a clean and economic synthetic method of amines,
because the catalyst, readily prepared from inexpensive
materials (nickel nitrate and θ-Al2O3), is easily separated
from the reaction mixture by centrifugation and is recyclable,
and good to excellent yield is achieved with a small amount of
the catalyst without any additives. The catalytic cycle is driven
by the hydrogen-borrowing mechanism. Structure−activity
relationship studies suggest that the active site for the reaction
can be metal/support interface, where low-coordinated Ni0
atoms are adjacent to the acid−base sites of alumina. It is
demonstrated that Ni catalyst, as a cheaper alternative to the
well established noble-metal catalysts, can be effective for a
hydrogen transfer reaction by controlling the size and oxidation
state of Ni, which will lead to a design of a practical catalyst for
These results indicate the hydride transfer pathway from the
alcohol to the imine via the Ni catalyst as well as the activity of
the Ni catalyst for the alcohol dehydrogenation step.
In Figure 5, initial reaction rates for the reaction of 1a and 2b
are plotted as a function of the initial concentration of 1a and
2b. The reaction rate slightly increased with the aniline
concentration up to 0.57 M, which corresponds to the reaction
order (n) of 0.17. At higher concentration, a slightly negative-
order dependence (n = −0.24) was observed. This result is
consistent with the above result that the imine formation from
benzaldehyde and aniline is very fast. The rate dependence on
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ACS Catalysis
Research Article
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* Supporting Information
Characterization data for catalyst and products. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: kshimizu@cat.hokudai.ac.jp. Fax: +81-11-706-9163.
Notes
The authors declare no competing financial interest.
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This work was supported by a “Grant for Advanced Industrial
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Industrial Technology Development Organization (NEDO)
and a MEXT program “Elements Strategy Initiative to Form
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