N-alkylation of amines with alcohols over alumina-entrapped Ag catalysts using the "borrowing hydrogen" methodology

Article abstract of DOI:10.1016/j.jcat.2012.05.007

Ag/Al₂O₃ catalysts were found to be highly active and selective in the N-alkylation of aniline with a variety of aromatic and linear alcohols. In the presence of a base, for example, Cs₂CO₃ or K₃PO₄ as promoter, high yields of secondary amines were obtained. The highest activity was found with 2.4 wt.% Ag/Al₂O ₃. The reaction involves the transient catalytic dehydrogenation of the alkylating alcohol to the corresponding carbonyl compound which then reacts spontaneously with the amine. In the final step, the hydrogen from the alcohol dehydrogenation step is transferred back to the imine, giving the secondary amine as the final product. With secondary amines, piperidine and pyrrolidine, the hemiaminal intermediate can undergo dehydrogenation as well as dehydration to give amides and amines, respectively. The heterogeneous nature of Ag/Al ₂O₃ allows for easy recovery and regeneration, which makes it an attractive system in the context of green and sustainable synthesis.

Full text of DOI:10.1016/j.jcat.2012.05.007

Journal of Catalysis 292 (2012) 130–137
Contents lists available at SciVerse ScienceDirect
Journal of Catalysis
journal homepage: www.elsevier.com/locate/jcat
N-alkylation of amines with alcohols over alumina-entrapped Ag catalysts
using the ‘‘borrowing hydrogen’’ methodology
⇑
Huihui Liu, Gaik-Khuan Chuah, Stephan Jaenicke
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Kent Ridge, Singapore 117543, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 February 2012
Revised 4 May 2012
Accepted 5 May 2012
Available online 8 June 2012
Ag/Al2O3 catalysts were found to be highly active and selective in the N-alkylation of aniline with a vari-
ety of aromatic and linear alcohols. In the presence of a base, for example, Cs2CO3 or K3PO4 as promoter,
high yields of secondary amines were obtained. The highest activity was found with 2.4 wt.% Ag/Al2O3.
The reaction involves the transient catalytic dehydrogenation of the alkylating alcohol to the correspond-
ing carbonyl compound which then reacts spontaneously with the amine. In the final step, the hydrogen
from the alcohol dehydrogenation step is transferred back to the imine, giving the secondary amine as the
final product. With secondary amines, piperidine and pyrrolidine, the hemiaminal intermediate can
undergo dehydrogenation as well as dehydration to give amides and amines, respectively. The heteroge-
neous nature of Ag/Al2O3 allows for easy recovery and regeneration, which makes it an attractive system
in the context of green and sustainable synthesis.
Keywords:
Alcohol
Amine
Amide
Heterogeneous catalysis
N-alkylation
Borrowing hydrogen
Silver
Ó 2012 Elsevier Inc. All rights reserved.
1. Introduction
In this reaction, the alcohol is formally dehydrogenated on the
catalyst and forms a carbonyl compound (an aldehyde from a pri-
Nitrogen-containing compounds such as amines and amides
constitute an important group of compounds that are of key impor-
tance in industrial chemical synthesis [1]. Among these nitrogen-
containing compounds, secondary amines are of particular value.
There are various methods to prepare them, including electrophilic
alkylation [2], reductive alkylation [2] and amination of aryl ha-
lides [3,4]. The reaction of primary amines with alkyl halides in
the presence of stoichiometric amounts of inorganic bases [5] is in-
deed the preferred laboratory method. Even though these proto-
cols have often reached excellent yield levels, there are
drawbacks associated with them, that is, low atom efficiency, high
waste/by-products production and low selectivity toward the de-
sired secondary amines because of the competing formation of
undesired tertiary amines and alkylammonium halides. One
approach could be the hydroamination of olefins and alkynes [6].
However, this method is severely limited by the availability of
the corresponding olefin and the electrophilic character of the
nitrogen reagent. Another promising protocol is the alkylation of
amines by alcohols using a reaction sequence that has been vari-
ously termed ‘‘hydrogen autotransfer,’’ ‘‘borrowing hydrogen
mechanism’’ or ‘‘self-supply system for active hydrogen’’ [7–12].
mary alcohol), whereas the hydrogen is bound to the catalyst as a
hydride species (Scheme 1). The carbonyl compound reacts with
the amine under elimination of one molecule of water to form
the imine. Hydrogenation of the imine with the abstracted hydro-
gen from the first step yields the desired amine. In summary, the
catalyst ‘‘borrows’’ a molecule of hydrogen and ‘‘auto transfers’’ it
to the intermediate imine to form the final product. There are
several advantages to this N-alkylation method, such as the ready
availability of the required alcohols and the high atom efficiency of
the transformation where both products from the alcohol dehydro-
genation (hydrogen and carbonyl compound) are used in the reac-
tion and water is formed as the only by-product [13]. In addition,
this process is highly selective to the desired amine as competing
self-condensation of the carbonyl substrate is minimized due to
its low concentration. Upon dehydrogenation of the alcohol, the
carbonyl substrate reacts to form an imine. This N-alkylation reac-
tion proceeds smoothly in the absence of an additional hydrogen
source. In contrast, reductive amination requires high concentra-
tion of the carbonyl substrate and high pressure of hydrogen for
good yields.
Many homogeneous transition metal catalysts [14–17], espe-
cially based on ruthenium [18–22] and iridium [23–28], have been
reported for this transformation. Watanabe et al. [18] used
RuCl2(PPh3)3 as the catalyst in the alkylation of aniline derivatives
⇑
Corresponding author. Fax: +65 6779 1691.
E-mail address: chmsj@nus.edu.sg (S. Jaenicke).
0021-9517/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jcat.2012.05.007

H. Liu et al. / Journal of Catalysis 292 (2012) 130–137
131
is important for the dehydrogenation step in the N-alkylation with
alcohols. To facilitate this interaction, we prepared the catalysts
following the procedure of Park’s group [47,48] where nanoparti-
cles of the active metal are entrapped in an in situ – generated
sol–gel alumina support. These authors have shown that such cat-
alysts have excellent activities for a variety of reactions [47–50].
Due to the intimate mixing, the heterogeneous system is expected
to offer a wide substrate tolerance and high catalytic activity.
Scheme 1. Hydrogen autotransfer process from alcohol to imine.
2. Experimental
by primary alcohols and obtained the corresponding N,N-dialkylat-
2.1. Synthesis of Al2O3-entrapped Ag catalysts
ed amines as the main product. Other examples include [Ru3(CO)12
]
and N-phenyl-2-(dicyclohexylphosphanyl)pyrrole [21], [Ru(p-cym-
ene)Cl2]2 with DPEPhos 60 as ligand [22] and [IrCpÃCl2]2 together
with a base [23]. The high cost of the stabilizing ligands coupled
with difficulties in the recovery and reuse is the drawback of these
homogeneous systems. Hence, the application of efficient, easily
recoverable and recyclable heterogeneous catalysts would be
clearly advantageous. One of the earliest examples of a heteroge-
Alumina-entrapped Ag catalysts were prepared with Ag load-
ings from 0.29 to 13 wt.%. In a typical synthesis for a 2.4 wt.% Ag/
Al2O3 sample, AgNO3 (63 mg/0.37 mmol) and aluminum tri-sec-
butoxide (8.32 ml/32.4 mmol) were dissolved in 2-butanol
(1.98 ml). The resulting gel was stirred at 100 °C for 3 h to give a
yellow suspension, following by the dropwise addition of deion-
ized water (4.5 ml). After stirring for another hour at 100 °C, the
suspension was cooled to room temperature and filtered. The solid
catalyst was washed with acetone, dried at 100 °C and calcined for
1 h at 600 °C (10 °C minÀ1 ramp). Prior to use, the catalyst was acti-
vated in flowing H2 at 300 °C for 30 min. The same procedure was
used to prepare a 2.4 wt.% Cu/Al2O3 catalyst except that copper
acetate was used as precursor for the metal.
neous catalyst for N-alkylation is silica gel [29]. Since then, c-alu-
mina [30], solid acids [31,32] and transition metal-based catalysts
such as Pd [33,34], Pt [35,36], Ru [37,38] and Ir [39] have been re-
ported. Concerns about the cost and availability of Pt-group metals
have spurred the search for alternative metal catalysts. He et al. [40]
used Cu(OH)x/Al2O3 and Cu(OH)x/TiO2 for the N-alkylation of
amines with activated benzylic alcohols. Although no cocatalyst
was required, treatment of the precursor catalyst with NaOH was
necessary for activity. Magnetite Fe3O4 also catalyzed N-alkylation,
but only between activated substrates, for example, aromatic
amines and benzylic alcohols [41]. Supported iron oxide nanoparti-
cles are active when used with a base, for example, 1,4-diaza-
bicyclo[2.2.2]octane (DABCO) or potassium or sodium tert-butoxide
under microwave irradiation where the temperatures are in the
range of 150–170 °C [42]. In general, the activity of these base metal
catalysts is lower than that of precious metals.
For comparative purpose, a 2.4 wt.% Ag sample was also synthe-
sized by impregnating 0.976 g of commercial
c-Al2O3 (Merck,
150 m2 gÀ1) with a 15 ml solution of silver nitrate (37 mg). The
suspension was stirred for 4 h at room temperature before increas-
ing the temperature to 90 °C to evaporate the water. After drying
overnight at 100 °C, the sample, 2.4 wt.% Ag/Al2O3–I, was calcined
and activated as for the alumina-entrapped Ag samples. The metal
content was determined by ICP-AES.
Silver is a feasible choice as it is less expensive than metals like
Au, Pt, Rh, Ir or Ru. However, due to its lower activity for C–H bond
activation, it is currently not as widely used in catalysis as the plat-
inum-group metals. Shimizu et al. [43] showed that alumina-sup-
ported silver in combination with FeCl3 as a Lewis acidic cocatalyst
formed an active system for the N-benzylation of anilines with
alcohols at 140 °C. The high catalytic activity with turnover num-
ber (TON) of 23 was attributed to a cooperation between coordin-
atively unsaturated sites on the very small silver particles
(diameter below 2 nm), acid/base sites on the alumina support
and the Lewis acidic Fe(III) cation. The same Ag/Al2O3 catalyst
was also active in the one-step synthesis of N-substituted anilines
from nitroaromatics and benzyl alcohols under 0.2 MPa hydrogen
pressure [44]. However, more base (20 mol.% KF) and a reaction
temperature of 155 °C were needed. Recently, Shimizu et al. [45]
investigated alumina-supported copper–silver bimetallic catalysts
for the N-alkylation reaction. They found that at 5 atom% Ag, this
catalyst was highly efficient in the alkylation of anilines and ali-
phatic amines with benzylic and aliphatic alcohols. The bimetallic
structure was proposed to be crucial in the promotion of alcohol
dehydrogenation as well as hydride transfer to the imines. The
reaction was carried out without any cocatalyst although a high
reaction temperature of 155 °C was required. Cui et al. [46] com-
bined the dehydrogenation ability of silver with the nucleophilic
2.2. Procedure for N-alkylation
Typically, the catalytic N-alkylation of benzyl alcohol and ani-
line was carried out using 1.5 mmol aniline and 3 mmol benzyl
alcohol in 5 ml p-xylene. The reaction mixture was placed in a
25-ml round bottom flask equipped with a condenser. After heat-
ing to 120 °C under N2, 0.165 g catalyst and 0.1 g base promoter
were added. Aliquots were removed at regular time intervals and
analyzed by gas chromatography. The products were identified
by gas chromatography–mass spectrometry (GC–MS).
For lower boiling substrates, the reaction was carried out under
He in a 50-ml Teflon-lined autoclave (Parr) equipped with mag-
netic stirring and sampling port. The reaction mixture consisted
of 3 mmol alcohol, 1.5 mmol amine and 5 ml p-xylene as solvent
together with 0.165 g catalyst and 0.1 g Cs2CO3.
2.3. Characterization
The textural properties of the catalysts were determined by
nitrogen adsorption (Micromeritics Tristar 2000). Prior to the mea-
surements, the each sample was degassed under N2 at 300 °C for
4 h. Powder X-ray diffraction (XRD) was measured with a Siemens
D5005 diffractometer equipped with variable slits and a copper an-
addition property of molybdenum. The hybrid oxide, Ag6Mo10O33
,
ode (CuK k 1.54056 Å). The diffractograms were recorded over a
a
together with K2CO3 or potassium tert-butoxide gave product
yields of 80–90% in the alkylation of amines, carboxamides, sulfon-
amides and ketones with aliphatic alcohols.
The previous studies on supported silver catalysts [43–45] show
that a close interaction between the support and the metal catalyst
2h range from 30° to 95°. The samples were examined by transmis-
sion electron microscopy (TEM, JEOL 3010) operated at 200 kV. The
finely ground sample was suspended in 2-propanol, and a drop
was placed onto a carbon-coated copper grid and dried before
TEM measurements.

132
H. Liu et al. / Journal of Catalysis 292 (2012) 130–137
3. Results and discussion
3.1. Textural properties
The textural properties of the catalysts are summarized in Table
1. The Ag/Al2O3 samples prepared by in situ generation of the sup-
port have high surface areas in excess of 250 m2 gÀ1 even after cal-
cination at 600 °C. For example, the 2.4 wt.% Ag/Al2O3 sample has a
surface area of 281 m2 gÀ1, which is almost twice that of the cata-
lyst prepared by wet impregnation onto c-Al2O3. The N2-sorption
isotherms of Ag/Al2O3 samples exhibit type IV isotherms with a
hysteresis loop at P/P° ꢀ 0.6–0.9, indicative of the presence of
mesopores (Fig. 1). As the Ag loading increased from 0.29 to
13 wt.%, the mean pore diameter decreased from 14.5 to 5.4 nm.
The highly porous nature of the samples is reflected in the large
pore volumes, which decreased from 2.2 to 0.54 cm3 gÀ1 with high-
er Ag content. This can be attributed to partial blockage of the
pores by the metal aggregates at higher metal loading.
For samples with 0.29–2.4 wt.% Ag, the powder X-ray diffracto-
grams showed only the broad peaks of c-Al2O3 support (Fig. 2). The
absence of reflexes due to Ag suggests that the metal is well dis-
persed on the support and/or that the crystalline size of Ag nano-
particles is below the detection limit of X-ray diffractometry,
typically less than 4 nm. Indeed, transmission electron micro-
graphs of 0.59 and 2.4 wt.% Ag/Al2O3 showed that the Ag nanopar-
ticles were smaller than ꢀ3 nm (Figs. S1 and S2). Only at higher Ag
loading, 6.2 and 13 wt.%, did the reflexes of crystalline Ag appear in
the X-ray diffractogram. This agrees well with a mean Ag particle
size of 4.5 nm observed in the transmission electron micrograph
of 6.2 wt.% Ag/Al2O3 (Fig. S3). In comparison with the alumina-en-
trapped Ag catalysts, the sample prepared by wet impregnation
(Fig. S4) had bigger Ag particles. Here, the (111) reflex of metallic
Ag could be clearly detected in the X-ray diffractogram even at
2.4 wt.% Ag (Fig. S5). Using the Scherrer equation, the Ag crystallite
size for 2.4 wt.% Ag/Al2O3–I was estimated to be 5.4 nm, which is
larger than the mean Ag particle size of 1.7 nm found in the alu-
mina-entrapped 2.4 wt.% Ag/Al2O3 sample.
Fig. 1. (i) Nitrogen adsorption–desorption isotherms and (ii) pore size distribution
of Ag/ -Al2O3 with (a) 0.29, (b) 0.59, (c) 1.2, (d) 2.4, (e) 6.2 and (f) 13 wt.% Ag.
c
3.2. Catalytic activity
use gave 29% conversion after 19 h (Table 2, entry 4). The interme-
diate imine, N-benzylideneaniline 1, and the secondary amine, N-
benzylaniline 2, were formed in almost equal amounts (51:49).
The addition of a base promoter, Cs2CO3, led to a tremendous in-
crease in the activity, so that >99% conversion was obtained (Table
2, entry 5). Equally striking is the very high selectivity, >99%, to N-
benzylaniline 2. Besides water, the only other product formed was
the imine 1. No tertiary amine 3 was observed. Activation of the
3.2.1. N-alkylation of aniline with benzyl alcohol
The activity of the catalysts was tested for the N-alkylation of
aniline with benzyl alcohol (Scheme 2). Benzyl alcohol and aniline
did not form any products in the absence of a catalyst (Table 2,
entry 1). Similarly,
c-Al2O3 synthesized from aluminum tri-sec-
butoxide and that obtained commercially showed no activity
(Table 2, entries 2 and 3). However, 2.4 wt.% Ag/Al2O3 prepared
from aluminum tri-sec-butoxide and hydrogen-activated before
Table 1
Textural properties of the catalysts.
Catalyst
S.A (m2/g)
Pore vol. (cm3/g)
Mean pore size (nm)
Metal particle size (nm)
0.29% Ag/Al2O3
0.59% Ag/Al2O3
1.2% Ag/Al2O3
2.4% Ag/Al2O3
6.2% Ag/Al2O3
13% Ag/Al2O3
2.4% Cu/Al2O3
2.4% Ag/Al2O3–Ia
273
360
326
281
257
262
319
150
300
112
1.6
2.2
1.1
0.73
0.76
0.54
0.34
0.27
0.33
0.24
14.5
17.4
9.3
7.7
6.5
5.4
4.0
4.5
3.5
5.6
n.d.
0.99c
n.d.
1.7c
4.5c
16
n.d.
5.4
n.d.
n.d.
b
5% Pd/Al2O3
b
5% Ru/Al2O3
a
b
c
Wet impregnation on commercial
Commercial sample from Degussa.
c-Al2O3.
From TEM measurements; all others from XRD measurements using the Scherrer equation; n.d.: not detected; particles below detection limit
of XRD (<4 nm).

H. Liu et al. / Journal of Catalysis 292 (2012) 130–137
133
Table 2
N-alkylation of aniline with benzyl alcohol by various catalysts.
Catalyst
Additive
Conv. (%)a
Selectivity (%)
1
2
3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
None
Cs2CO3
Cs2CO3
Cs2CO3
–
None
None
None
29
>99
61
>99
45
17
43
96
77
26
–
–
–
51
1
56
1
96
77
39
1
64
97
90
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
Synthesized Al2O3
Commercial Al2O3
2.4% Ag/Al2O3
2.4% Ag/Al2O3
2.4% Ag/Al2O3
2.4% Ag/Al2O3
2.4% Ag/Al2O3–I
2.4% Ag/Al2O3
2.4% Ag/Al2O3
2.4% Ag/Al2O3
2.4% Cu/Al2O3
5% Pd/Al2O3
49
99
44
99
4
23
61
99
36
3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Na2CO3
K2CO3
K3PO4
Cs2CO3
Cs2CO3
Cs2CO3
b
c
Fig. 2. XRD diffractograms of (a)
c-Al2O3 and Al2O3-entrapped samples with (b)
5% Ru/Al2O3
75
10
0.29, (c) 0.59, (d) 1.2, (e) 2.4, (f) 6.2 and (g) 13 wt.% Ag.
Reaction conditions: benzyl alcohol (3 mmol), aniline (1.5 mmol), catalyst
(165 mg), promoter (100 mg), xylene (5 ml), 120 °C, under N2.
a
After 19 h.
Without H2 activation.
Treated in flowing N2 (300 °C/3 h) after H2 activation.
b
catalyst by pretreatment in a hydrogen flow is essential; without
this activation step, the conversion was only 61% and the selectiv-
ity to N-benzylaniline 2 was reduced to 46% with N-benzylide-
neaniline 1 being the predominant product (Table 2, entry 6).
The hydrogen pretreatment results in the formation of active
metallic silver particles and the removal of any adsorbed oxygen.
In order to verify whether the hydrogen incorporated into N-ben-
zylaniline 2 comes from hydrogen adsorbed at the metal surface
during the pretreatment or from the dehydrogenation of benzyl
alcohol, the reduced catalyst was flushed with N2 at 300 °C for
3 h. The activity and selectivity of the reaction was unaffected by
this treatment (Table 2, entry 7), indicating that the hydrogen
incorporated into N-benzylaniline 2 comes indeed from the dehy-
drogenation of benzyl alcohol. Comparing the activity of Al2O3-en-
trapped Ag catalyst with that prepared by wet impregnation, it was
found that the conversion after 19 h over the impregnated catalyst,
2.4% Ag/Al2O3-I, was only 45% (Table 2, entry 8), while 2.4% Ag/
Al2O3 had >99% conversion. Furthermore, over 2.4% Ag/Al2O3-I,
the major product was N-benzylideneaniline 1 (96% selectivity)
and not N-benzylaniline 2. The predominant formation of the
imine may be due to a poorer hydrogenation capability of the sam-
ple, possibly due to the lower reactivity of the atoms at the surface
of bigger Ag clusters (mean size 5.4 nm) as compared to that for
2.4% Ag/Al2O3 (mean size 1.7 nm). Shimizu et al. [43] also reported
a drop in turnover frequency and amine selectivity for Ag clusters
above 2 nm.
c
Fig. 3. Initial rate (ꢀ) and TOF based on total metal (h) for N-alkylation of aniline by
benzyl alcohol over Al2O3-entrapped Ag catalysts.
The promotional effect of a base in the dehydrogenation of alcohols
to form ketones and aldehydes has been observed in both homoge-
neous and heterogeneous catalytic systems [16,51,52]. It is pro-
posed that the base helps in the deprotonation of the primary
alcohol to form an alkoxide and also facilitates the removal of a hy-
dride from it.
As the addition of Cs2CO3 increased the activity significantly,
other basic promoters were investigated (Table 2, entries 9–11).
The results show that K3PO4 is also an effective promoter with
96% conversion of aniline and >99% selectivity to benzylaniline 2.
Scheme 2. N-alkylation of aniline with benzyl alcohol.

134
H. Liu et al. / Journal of Catalysis 292 (2012) 130–137
The catalytic activity of 2.4 wt.% Ag/Al2O3 in the presence of the
rate and based on the total Ag content, decreased by more than
an order of magnitude, from 13 to 1.2 hÀ1, as the Ag loading in-
creased from 0.29 to 13 wt.%. Similarly, the TOF based on the num-
ber of surface Ag atoms also decreased, from 15 to 7.5 hÀ1 for the
0.59–13 wt.% Ag/Al2O3 (Fig. S8). The number of surface Ag atoms
was estimated based on the mean diameter of the silver crystallites
obtained from TEM and XRD measurements [53,54]. The TEM
micrographs show that as the Ag loading increased from 0.59 to
6.2 wt.%, the mean crystallite size increased from 1.0 to 4.5 nm.
Smaller crystallites offer a higher density of coordinatively unsatu-
rated sites. Such edge and corner atoms are often the active sites
for reaction due to their higher reactivity. Furthermore, in the big-
ger crystallites, the number of Ag atoms adjacent to the support is
reduced. The interaction of Ag with the acid–base sites of alumina,
and the promoter plays a significant role in the catalytic cycle [43].
This explains the decrease in TOF with the increasing particle size,
even in the case that the TOF is normalized to surface atoms only.
The activity of our catalysts with 0.59–6.2 wt.% Ag corresponds
to turnover numbers (TONs) of 16–75. This compares well with the
reported turnover numbers of 18 and 23 for 5 mol.% Ru(OH)x/Al2O3
promoter is higher than that of 5% Ru/Al2O3 and 5% Pd/Al2O3. After
19 h, full conversion was obtained for 2.4 wt.% Ag/Al2O3, but the
conversion was only 26% and 75% for 5% Pd/Al2O3 and 5% Ru/
Al2O3, respectively. Comparing the activity on a molar basis, the
intrinsic activity decreased from 41, 13 and 5 mol aniline
converted/mol metal for the alumina-supported Ag, Ru and Pd
catalysts, respectively. For the Ru and Pd catalysts, the main
product was the secondary imine 1, showing that these catalysts
were not as efficient in hydrogenating the intermediate imine to
N-benzylaniline as Ag. Surprisingly, the Al2O3-entrapped copper
catalyst (Figs. S6 and S7) was more active (18 mol/mol Cu) than
the supported Ru or Pd catalysts. However, at 2.4 wt.% loading,
the selectivity toward the benzylaniline 2 was only 36% as com-
pared to >99% for the silver-based catalyst.
To optimize the N-alkylation of aniline by benzyl alcohol, the
effect of silver loading on the Ag/Al2O3 catalyst was studied. The
initial reaction rate (determined from conversion after 1 h) in-
creased steeply up to 2.4 wt.% Ag before decreasing slightly
(Fig. 3). The turnover frequency (TOF), calculated from the initial
Table 3
N-Alkylation of amines with alcohols.
Amine
Alcohol
Products
Conv.
(%)
Sel. (%)
Amine
99
Imine
1
Amide
–
1
>99
NH2
OH
NH
95a
97b
88
5
3
12
2
3
98
54
–
–
NH2
NH2
NH2
NH2
OH
NH
16
84
OH
NH
NH
4
5
CH3OH
<1
5
–
–
–
–
>99
<1
H
N
OH
6
7
8
25
69
<1
80
>99
–
20
<1
–
–
–
–
NH2
NH2
NH2
NH2
H
N
OH
H
N
OH
CH3(CH2)17OH
H
N
CH3
(CH2)17
9
15
9
<1
7
>99
93
–
–
N
OH
OH
10
NH2
NH2
N
11
12
95
51
<1
24
>99
–
–
OH
OH
N
76
H
N
N
N
N
O
13
18
22
–
78
H
N
OH
N
O
Reaction condition: alcohol (3 mmol), amine (1.5 mmol), 2.4 wt.% Ag/Al2O3 (165 mg), Cs2CO3 (100 mg), xylene (5 ml), 120 °C, entry 1: under N2, entries 2–13: autogenous
pressure plus 1 atm He in autoclave.
a
First time recycled.
Second time recycled.
b

H. Liu et al. / Journal of Catalysis 292 (2012) 130–137
135
[37] and 5 wt.% Ag/Al2O3 [43], respectively. Furthermore, the reac-
tion temperatures for these catalysts were higher (132 and 140 °C)
than the 120 °C used in this study.
with large amounts of 2-propanol, followed by acetone and reacti-
vated in H2 at 300 °C. The rate of reaction was very similar to the
fresh catalyst, and N-benzylaniline was formed with 95–97% selec-
tivity at >99% conversion (Table 3, entry 1).
3.2.2. Other substrates
The N-alkylation of other substrates was investigated using the
heterogeneous 2.4 wt.% Ag/Al2O3 catalyst in an autoclave at autog-
enous pressure (plus 1 atm He). The rate of N-alkylation of aniline
increased with the chain length of linear alkyl alcohols (Table 3,
entries 4–7). In all cases, the main product was the secondary
amine. With methanol, the reaction was sluggish, and less than
1% N-methylaniline was formed. With 1-butanol and 1-pentanol,
5% conversion and 25% conversion were observed, respectively,
after 19 h. 1-Hexanol (Table 3, entry 7) reacted with aniline to give
a satisfactory yield of 69% N-hexylaniline. However, no reaction oc-
curred when long-chained 1-octadecanol was used as the alkylat-
ing agent (Table 3, entry 8). Possibly, the long C18 chain poses a
steric hindrance in the transformation steps to the amine, in addi-
tion to diffusion limitations due to its bulkier size. Indeed, the reac-
tion between cyclohexylmethanol and aniline gave only 15%
conversion after 19 h. The predominant product was the imine,
N-(cyclohexylmethylene)aniline (Table 3, entry 9) formed with
the elimination of an equivalent of H2. Alkylation of secondary
amines, 1-phenylethanamine and cyclohexylamine, with benzyl
alcohol also yielded imines as the major product (Table 3, entries
10 and 11). These results suggest that hydrogenation of the imines
could be rate-determining due to steric hindrance. Interestingly,
the secondary amines, piperidine and pyrrolidine (Table 3, entries
12 and 13) formed tertiary amines as well as amides. The latter
was the major product with 76–78% selectivity. The hemiaminal
formed from the secondary amine and the carbonyl species prefer-
entially undergoes dehydrogenation rather than dehydration.
3.2.4. Mechanistic studies
In the N-alkylation of aniline with benzyl alcohol catalyzed by
2.4 wt.% Ag/Al2O3, only two products, N-benzylideneaniline 1 and
N-benzylaniline 2, were detected. The reaction profile shows the
consecutive transformation of aniline first to 1 and then to 2
(Fig. 5). The concentration of 1 increased to a maximum at 4 h be-
fore decreasing with time as it transformed to 2. From the activity
results with and without a base (Table 2), we postulate that a cru-
cial step is the formation of benzaldehyde from benzyl alcohol. We
have previously reported that K3PO4 is a highly efficient solid base
catalyst in the catalytic transfer hydrogenation of aldehydes using
alcohols without needing a metal catalyst [55]. The low reaction
rate when the catalyst is present without the base (Table 2, entry
4) as compared to the rate enhancement when present together
(Table 2, entries 5 and 11) shows the synergistic effect of Ag/
Al2O3 and Cs2CO3 (or K3PO4). However, without any hydrogen
acceptor, for example, oxygen or imine, the presence of the catalyst
and base promoter is not enough to catalyze the dehydrogenation
of benzyl alcohol to benzaldehyde. A low yield of <2% was recorded
(Table 4, entry 1). The addition of a hydrogen acceptor such as N-
benzylideneaniline 1 is necessary for dehydrogenation to occur,
and benzaldehyde was formed in 15% yield (Table 4, entry 2).
The coupling of benzaldehyde with aniline yielded 100% N-benzy-
lideneaniline 1 within 1 h without needing any catalyst (Table 4,
entry 3). Using gaseous hydrogen, N-benzylideneaniline 1 was
readily reduced to N-benzylaniline 2 with a yield of 80% (Table 4,
entry 4). In comparison, the catalytic transfer hydrogenation of 1
with benzyl alcohol proceeded efficiently over the Ag/Al2O3 cata-
lyst to give 61% yield of 2 (Table 4, entry 2). An inert atmosphere
is essential to ensure that the reaction can proceed to the desired
product 2 because under aerobic conditions, aniline and benzyl
alcohol react to give exclusively 1 (Table 4, entry 5).
3.2.3. Heterogeneity of reaction and reuse of catalyst
In order to test for leaching and to confirm that the reaction is
indeed heterogeneously catalyzed, the reaction was allowed to
run initially in the presence of 2.4% Ag/Al2O3 catalyst (Fig. 4). After
2 h, the catalyst was removed from the reaction mixture by centri-
fugation. The clear supernatant was again brought to reaction con-
ditions. Over a period of next 16 h, the conversion remained
unchanged and no further reaction was observed. These experi-
ments confirm that the active phase did not leach from the catalyst
under the reaction conditions.
Based on these observations, we propose that the reaction pro-
ceeds with the transitory formation of the Ag hydride species
(Scheme 3). The role of the base is connected with the dehydroge-
nation step to form the carbonyl compound since the reaction of
the imine to amine proceeds smoothly without base. Possibly,
the base aids in deprotonation of the alcohol to form an alkoxide
at a Lewis acid site of the alumina support. The removal of a
The activity of 2.4% Ag/Al2O3 was tested for reuse. Following the
batch reaction, the catalyst was recovered by filtration, washed
Fig. 5. Reaction profile for N-alkylation of aniline by benzyl alcohol over 2.4 wt.%
Ag/Al2O3. (ꢀ) Aniline, (d) N-benzylideneaniline and (h) N-benzylaniline. Reaction
conditions: benzyl alcohol (3 mmol), aniline (1.5 mmol), xylene (5 ml), catalyst
(165 mg), Cs2CO3 (100 mg), 120 °C.
Fig. 4. N-alkylation of aniline with benzyl alcohol in the presence of 2.4 wt.% Ag/
Al2O3 (N) and after catalyst removal at 2 h (e).

136
H. Liu et al. / Journal of Catalysis 292 (2012) 130–137
Table 4
Reaction studies and conditions.
Reaction
1
Conditions
He (1 bar) 2.4 wt.% Ag/Al2O3 (165 mg), Cs2CO3 (100 mg) 120 °C, 19 h
O
OH
H
+
H
2
3 mmol
< 2 %yield
2
He (1 bar) 2.4 wt.% Ag/Al2O3 (165 mg), Cs2CO3 (100 mg) 120 °C, 19 h
O
H
N
N
OH
H
+
+
61 %
15 %
24 %
4mmol
1mmol
3
He (1 bar) 120 °C, 1 h
O
NH
2
N
H
+
OH
+
100%
3 mmol
N
1.5 mmol
4
5
H2 (1 bar), 2.4 wt.% Ag/Al2O3 (165 mg) 120 °C, 19 h
H
H
2
N
80 %
Open to air, 2.4 wt.% Ag/Al2O3 (165 mg), Cs2CO3 (100 mg), 120 °C, 25 h
NH2
N
OH
3 mmole
+
H2O
+
1.5 mmole
100%
4. Conclusion
Silver-based catalysts were generated by in situ precipitation of
silver particles in an aluminum oxyhydroxide support followed by
calcination at 600 °C. The resulting Ag/Al2O3 samples were active
for the N-alkylation of amines with alcohols with 2.4 wt.% Ag being
optimal. The higher activity compared to samples prepared by wet
impregnation shows that an intimate mixing of silver and the
support is important. The addition of Cs2CO3 or K3PO4 as a base
promoter improved the activity and selectivity to amines. N-Ben-
zylaniline was formed in >99% yield from aniline and benzyl
alcohol. The base promoter is necessary for the efficient dehydro-
genation of the alcohol to the corresponding carbonyl compound
that then reacts spontaneously with the primary or secondary
amine to form the imine. Hydrogenation of the imine to the desired
amine takes place under an inert atmosphere using the self-gener-
ated hydrogen from the alcohol dehydrogenation step. In addition
to the tertiary amines, amides were formed when piperidine and
pyrrolidine were reacted with benzyl alcohols. The heterogeneous
Ag/Al2O3 can be recycled and reused without loss of activity and
selectivity.
Acknowledgment
Financial support from National University of Singapore under
Grant number R-143-000-374-112 is gratefully acknowledged.
Scheme 3. Proposed reaction steps for the N-alkylation of primary and secondary
amines by alcohol catalyzed by Ag/Al2O3.
Appendix A. Supplementary material
hydride from the alkoxide by the Ag catalyst leads to the formation
of the carbonyl compound. The carbonyl compound readily reacts
with a primary amine to form the corresponding imine. Finally, the
hydride and a proton from the alumina are transferred back to the
imine to afford the corresponding secondary amine. Starting with a
secondary amine, both the amine and amide can form. Due to sta-
bilization by the electron donating alkyl substituents of the sec-
ondary amine, the hemiaminal intermediate has a longer life
time than that formed from a primary amine. Hence, it can under-
go further hydride elimination forming the amide. Imine-like inter-
mediates are readily hydrogenated to the amine.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.jcat.2012.05.007.
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