Highly active and selective gold catalysts for the aerobic oxidative condensation of benzylamines to imines and one-pot, two-step synthesis of secondary benzylamines

Article abstract of DOI:10.1016/j.jcat.2009.03.015

Supported gold nanoparticles catalyze the oxidation of benzylamines to N-benzylidene benzylamines by molecular oxygen in toluene. The process is general, and para-substituted benzylamines as well as heterocyclic methanamines undergo oxidative condensation. 1-Phenylethanamine and diphenylmethanamine form imines with much less selectivity than benzylamines due to the unfavourable steric hindrance introduced by the substituents at the α-carbon. Secondary and tertiary dibenzyl and tribenzylamines form N-benzylidene benzylamines accompanied with aromatic ketones and oximes arising from C-N bond rupture. The efficiency of gold catalyst increases exponentially as the average particle size is reduced, and the TOF increases when the gold crystallite size is decreased. The solid support plays an important role as it has been found that gold supported on active carbon is more efficient than gold supported on anatase. Although palladium nanoparticles are also active in promoting benzylamine oxidation, only the catalyst based on platinum was found to exhibit an activity comparable to that of gold. Cross condensation of benzylamines in the presence of aromatic or aliphatic primary amines forms the mixed N-aryl or N-alkyl benzylimines with high yields. A one-pot, two-step procedure using a single gold catalyst has been devised to produce secondary symmetric and asymmetric amines derived from benzylamines with high atom efficiency.

Full text of DOI:10.1016/j.jcat.2009.03.015

Journal of Catalysis 264 (2009) 138–144
Contents lists available at ScienceDirect
Journal of Catalysis
journal homepage: www.elsevier.com/locate/jcat
Highly active and selective gold catalysts for the aerobic oxidative condensation of
benzylamines to imines and one-pot, two-step synthesis of secondary benzylamines
*
*
Abdessamad Grirrane, Avelino Corma , Hermenegildo Garcia
Instituto de Tecnología Química CSIC-UPV, Universidad Politécnica de Valencia, Av. De los Naranjos s/n, 46022 Valencia, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Supported gold nanoparticles catalyze the oxidation of benzylamines to N-benzylidene benzylamines by
molecular oxygen in toluene. The process is general, and para-substituted benzylamines as well as het-
erocyclic methanamines undergo oxidative condensation. 1-Phenylethanamine and diphenylmethan-
amine form imines with much less selectivity than benzylamines due to the unfavourable steric
Received 24 February 2009
Revised 24 March 2009
Accepted 25 March 2009
Available online 8 May 2009
hindrance introduced by the substituents at the a-carbon. Secondary and tertiary dibenzyl and tribenzyl-
amines form N-benzylidene benzylamines accompanied with aromatic ketones and oximes arising from
C–N bond rupture. The efficiency of gold catalyst increases exponentially as the average particle size is
reduced, and the TOF increases when the gold crystallite size is decreased. The solid support plays an
important role as it has been found that gold supported on active carbon is more efficient than gold sup-
ported on anatase. Although palladium nanoparticles are also active in promoting benzylamine oxidation,
only the catalyst based on platinum was found to exhibit an activity comparable to that of gold. Cross
condensation of benzylamines in the presence of aromatic or aliphatic primary amines forms the mixed
N-aryl or N-alkyl benzylimines with high yields. A one-pot, two-step procedure using a single gold cat-
alyst has been devised to produce secondary symmetric and asymmetric amines derived from benzylam-
ines with high atom efficiency.
Keywords:
Gold catalysis
Aerobic oxidation
Benzylamine oxidation
Secondary amine synthesis
Ó 2009 Elsevier Inc. All rights reserved.
1. Introduction
the reagent from oxygen to hydrogen, it is possible to obtain sym-
metric and asymmetric secondary amines with very high atom effi-
Considerable progress has been made in the recent years in
developing catalytic oxidations using oxygen as the final oxidizing
reagent [1,2]. In this regard, supported metal nanoparticles are
selective and efficient catalysts to promote the aerobic oxidative
condensation of alcohols and aldehydes [3–9].
ciency. High atom efficiency is one of the major requirements in
green chemistry and it is fulfilled with the process reported here
[22].
A precedent to our work is the very recent reports from Angelici
using bulk gold metal of micrometric size and alumina-supported
gold nanoparticles (size distribution 50–100 nm) as catalysts for
the aerobic oxidative condensation of benzylamine [23,24]. The
main point of these reports is the unexpected activity of bulk gold
as catalysts. In principle, it could be anticipated that by decreasing
the gold crystallite size the activity of gold should increase. By pre-
paring Au/TiO2 samples with different metal crystallite sizes, we
will show that the oxidation of benzylamines is a structure sensi-
tive reaction. The Au/TiO2 catalyst, which is also active in the
hydrogenation of imines, has been found to be much less active
than the Au/C catalyst in the oxidation of benzylamines, but more
active in the hydrogenation of imines. Therefore, using gold as a
single catalyst it has been possible to perform a one-pot, two-step
process in which the initial benzylidene amine formation is cou-
pled with subsequent hydrogenation using the same catalyst
(Scheme 1). The overall result of this one-catalyst, two-step pro-
cess is a novel route for symmetric and asymmetric secondary ben-
zylamines with very high atom efficiency.
In contrast to the interest for alcohol oxidation, catalytic oxida-
tion of amines has attracted considerably less attention due to poor
product selectivity typically achieved with these substrates [10–
12]. Recently, we have reported that gold is a highly active and
selective catalyst for the aerobic oxidative condensation of anilines
to azobenzenes [13]. As a continuation of this work on amine oxi-
dation, herein, we present the selective aerobic oxidative conden-
sation of benzylamines to N-benzylidene benzylamines (Scheme
1). Benzylimines are useful synthetic intermediates that can un-
dergo a large variety of transformations of the C@N double bond
including hydrogenations, [2+2] cycloadditions and nucleophilic
additions (the so-called Strecker reaction) [14–21]. Furthermore,
following a one-pot, two-step (oxidation followed by hydrogena-
tion) strategy in which the same gold catalyst is used, but changing
* Corresponding authors. Fax: +34 96 387 7809.
E-mail addresses: acorma@itq.upv.es (A. Corma), hgarcia@qim.upv.es (H. Garcia).
0021-9517/$ - see front matter Ó 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.jcat.2009.03.015

A. Grirrane et al. / Journal of Catalysis 264 (2009) 138–144
139
NH
H
2
O
N
H
2
N
2
-NH
R
R
R
3
R
R
1a-c
2a-c
3a-c
Scheme 1. Oxidative condensation of benzylamines to N-benzylidene phenylmethanamines and secondary amines.
sealing the reactor, air was purged by filling the reactor with oxy-
gen (5 bar) and by pumping out three times before final pressuri-
zation of the reactor with O2 at 5 bar. The reactor was deeply
introduced into a silicone bath that was preheated at 373 K. During
the experiment, the pressure was maintained constant and the
reaction mixture was magnetically stirred at 1000 rpm. Aliquots
were taken from the reactor at different reaction times. Once the
catalyst particles were removed from the solution by centrifuging
at 12000 rpm, the products were analyzed by GC–MS and also by
comparing the retention time with commercial (Sigma–Aldrich
Company) pure samples. Only experiments with mass balances
P95% were considered.
In the cases of experiments with a one-catalyst, two-step pro-
cess in which the initial imine formed in the cross condensation
is subsequently reduced to the secondary amine, the experimental
conditions were the same as in the initial oxidation step. Once this
reaction was complete, the hydrogenation step was carried out by
flushing out the O2 at room temperature and after sealing the reac-
tor, hydrogen (7 bar) was charged. Then, the reactor was deeply
introduced in the silicone bath that was preheated at the required
temperature.
2. Experimental
2.1. Catalyst preparation
The Au/TiO2 catalyst consists of 1.5 wt% gold supported on TiO2,
and was supplied by the World Gold Council (reference catalysts,
Type A). It can also be prepared by depositing the gold from an
aqueous solution of HAuCl4 (Alfa Aesar) on a sample of TiO2 (P25
Degussa). The deposition precipitation procedure is done at
343 K and pH 9 for 2 h, using (0.2 M) NaOH to maintain the pH
constant. Under these conditions, gold deposition occurs with
80% efficiency. The catalyst is then recovered, filtered, washed with
deionized water and dried at 373 K overnight. Finally, the powder
is calcined at 673 K in air for 4 h. Following this procedure, 3.5 nm
gold nanoparticles supported on TiO2 are obtained.
The Au/C catalyst consists of 0.8 wt% gold supported on active
carbon, and was also supplied by the World Gold Council (refer-
ence catalysts, Type D).
The Au/Al2O3 catalyst consists of 5 wt% gold supported on
Al2O3, and was prepared by incipient wetness impregnation of
4.0 g of
-Al2O3 (specific surface area of 158 m2/g) with a solution
c-
c
of 0.42 g of HAuCl4 ꢀ 3H2O in 2 ml of H2O (pH 9, milliQ). The
impregnation procedure is done in air and the sample was allowed
to dry overnight at room temperature. After drying in an oven at
383 K for 1 h, the solid was reduced under H2 flow with heating
at a rate of 3 K/min from room temperature to 573 K for 1 h. The
catalyst was exhaustively washed with distilled water until no
traces of chlorides were detected by the AgNO3 test. The removal
of Clꢁ ions is an important process since traces of Clꢁ remain
strongly bonded to gold, and are highly detrimental for the overall
activity. Finally, the powder is calcined at 973 K in air for 20 h. Fol-
lowing this procedure, 50–150 nm gold nanoparticles supported
3. Results and discussion
When we were working with the supported gold nanoparticles
catalysts for the oxidation of benzylamines, Angelici and co-workers
[23,24] reported that the nanoparticles of gold with 50–100 nm
were also able to perform the oxidation reaction. From these results,
we ascertained that the direction to increasing catalyst activity was
indeed to work on supported gold since, in principle, smaller gold
crystallites are more active than the larger bulk gold particles as re-
ported by Angelici and co-workers [23,24]. Then, we will present
firstly the role of the gold crystallite size on the activity and selectiv-
ity for the aerobic oxidative condensation of benzylamines.
It has been reported that it is possible to prepare Au/TiO2 cata-
lysts with the same gold content and different crystallite sizes by
depositing gold at different pHs [25–29]. Following this, three
Au/TiO2 samples were prepared, and the TEM analyses of the
resulting samples (see Fig. 1) show that the Au/TiO2 catalysts with
different metal particle sizes were obtained.
When the initial reaction rate (measured from the initial slope
of the plot of conversion vs. reaction time) for the oxidation of ben-
zylamine 1a on the three samples was determined, the results
show (Fig. 2) that there is a not linear but exponential increase
of activity when decreasing the crystallite size, being the activities
of the Au/TiO2 samples much larger than with gold on alumina (see
Fig. 2 and Table 1).
on
c-Al2O3 are obtained.
Pd/TiO2 (5 wt%) and Pt/TiO2 (5 wt%) catalysts were prepared by
the impregnation of 2 g of TiO2 (Degussa P25, 10 g,
SBET = 55 m2 gꢁ1) with a solution of 0.345 g of PdCl2 (Aldrich, 60%
purity) or 0.28 g of H2PtCl6 ꢀ 6H2O (Aldrich) in 7 ml of H2O (milliQ).
The slurry was stirred for 2 h at room temperature, then all the li-
quid was evaporated and the solid was dried at 373 K overnight
and reduced with 1-phenylethanol at 433 K for 2 h. The catalyst
was then washed, filtered and dried at room temperature for
12 h. The final Pd/or Pt content was found to be 5 wt% by atomic
absorption analysis.
2.2. Catalytic experiments
Catalytic experiments were performed in reinforced glass semi
continuous reactors equipped with temperature and pressure con-
trollers. For each reaction, a 2 ml mixture of reactants and solvent
was placed into the reactor (3 ml capacity) together with the
appropriate amount of catalyst. Using toluene as a solvent, care
has to be taken to avoid vapour mixtures within the explosion
range. Working under the experimental conditions 373 K and
5 bar of oxygen, the composition of the vapour phase is outside
the explosion mixture range. All the reactants used in this study
are commercially available from Sigma–Aldrich Company with
purities higher than 95%. Dodecane was always used as an internal
standard for the determination of conversion level and yields. After
The exponential increase of the initial reaction rate when
decreasing the size of the gold crystallites and the fraction of metal
surface atoms indicates that the oxidation of benzylamine to give
N-benzylidene benzylamine must be a structure sensitive reaction
and consequently not all the gold surface atoms are equally active.
Then, from the activity results it could be expected that unsatu-
rated gold atoms located at the corners of the crystallites, and
which are proportionally numerous when decreasing the gold
crystal size, should be more active.
If this is the case a higher activity for the oxidation of benzyl-
amine to give N-benzylidene benzylamine should be obtained with

140
A. Grirrane et al. / Journal of Catalysis 264 (2009) 138–144
120
90
60
30
0
2
2.5
3
4
5
diameter (nm)
90
60
30
0
4.5
5
5.5
6
7
diameter (nm)
200 nm
75
50
25
0
15
17
23
25
27
35
diameter (nm)
200 nm
Fig. 1. TEM images and particle size distribution of three Au/TiO2 catalysts used in this work having a very different average gold nanoparticles sizes.
Table 1
75
50
25
0
Average particle size (hdi), TOF, conversion and selectivity for benzylamine oxidation
catalyzed by a series of gold catalysts with different size particle sizes.
Catalyst
0.8 wt%
Au/C
1.5 wt%
Au/TiO2
1.2 wt%
Au/TiO2
Au/TiO2
Au/Al2O3
hdi (nm)
10
280
1
99
100
3.5
70
30
98
94
5.5
20
30
76
98
25
0
30
58
97
69
0
30
48
97
TOF (hꢁ1
)
a
Time (h)b
Conversion (%)
Selectivity (%)
a
TOF = r0/nmetal. r0 = initial reaction rate measured from the slope of the time
0
5
10
15
20
25
30
conversion plot at zero time. For reaction conditions, see Table 2.
b
<d> nm
Results of the conversion and selectivity towards N-benzylidene phenylamine
2a for the oxidation of benzylamine 1a by oxygen in the presence of gold catalysts
Fig. 2. Plot of the turnover frequency (TOF determined from the initial reaction rate
divided by the number of gold atoms) for benzylamine oxidation vs. the average
size of the gold nanoparticles for the Au/TiO2 series. For reaction conditions, see
Table 2.
with different particle sizes.
(see Fig. 3) and an average crystallite size larger than that of the
most dispersed Au/TiO2 (BET surface area = 50 m2 gꢁ1) sample
was found. Interestingly, the catalytic activity for the oxidation of
benzylamine on Au/C turns out to be much higher than that with
Au/TiO2 (see Fig. 4).
a catalyst with a higher gold dispersion. In an attempt to achieve a
higher metal dispersion we have used gold on high surface area ac-
tive carbon. Thus, a 0.8 wt% Au/C was obtained from the World
Gold Council [30], with a BET surface area of 1100 m2 gꢁ1. How-
ever, the crystallite size of gold in Au/C was measured by TEM
In order to explain this observation, and since a strong gold/me-
tal support interaction cannot be expected for carbon, we have to

A. Grirrane et al. / Journal of Catalysis 264 (2009) 138–144
141
80
60
40
20
0
8
9
10
11
12
13
14
15
diameter (nm)
200 nm
Fig. 3. TEM (left) and particle size distribution (right) of the 0.8 wt% Au/C catalyst used in this work.
Table 2
100
75
50
25
0
Conversion and selectivity towards N-benzylidene phenylamine 2a–c for the
oxidation of benzylamines 1a–c by oxygen in the presence of gold catalysts. Reaction
conditions: benzylamine, 1 mmol; toluene, 2 ml; oxygen pressure, 5 bar; tempera-
ture, 373 K; and Au/substrate mol ratio, 1%.
Substrate Catalyst
Time
(h)
Product Conversion
(%)
Selectivity
(%)
1a
1.5% Au/TiO2
1.5% Au/TiO2 (first
reuse)
1.5% Au/TiO2 (second
reuse)
30
30
2a
98
75
94
98
30
66
99
0
5
10
15
20
25
30
35
-25
0.8% Au/C
1
1
1
99
95
72
100
100
100
0.8% Au/C (first reuse)
0.8% Au/C (second
reuse)
0.8% Au/C (third
reuse)
Time (h)
Fig. 4. Time–yield plots for the oxidation of phenylmethanamine 1a in the presence
of 0.8 wt% Au/C (10 nm) (ꢀ), 1.5 wt% Au/TiO2 (3.5 nm) (j), 1.2 wt% Au/TiO2 (5.5)
(M), 1.5 wt% Au/TiO2 (25 nm) (ꢂ) and 5 wt% Au/Al2O3 (69 nm) (*) to the
corresponding N-benzylidene phenylmethanamine 2a. Reaction conditions: ben-
zylamine, 1 mmol; toluene, 2 ml; oxygen pressure, 5 bar; temperature, 373 K; and
Au/substrate mol ratio, 1%.
1
68
100
5% Pd/TiO2
5% Pt/TiO2
30
22
77
99
97
97
1b
1c
1.5% Au/TiO2
0.8% Au/C
22
1
2b
2c
99
99
94
99
1.5% Au/TiO2
0.8% Au/C
45
1.5
74
100
92
100
assume that in the case of Au/C, the catalyst may exhibit a large
number of very small particles that are difficult to be seen and to
be measured by TEM, and that are very active [31,32]. Note that
the initial reaction rate is more than one order of magnitude larger
for Au/C than for Au/TiO2, which makes it possible for the former to
produce full conversion, with practically 100% selectivity in less
than 1 h reaction time, while 30 h is necessary to achieve almost
100% conversion with 94% selectivity with Au/TiO2 (see Table 2).
Concerning the reaction mechanism and the role of oxygen as a
final oxidizing agent, we analyzed the vapour phase after the reac-
tion to determine the presence of some nitrogen compounds. As
shown in Scheme 1, the aerobic oxidative coupling expels one
nitrogen atom. It was of interest to determine if ammonia, hydrox-
ylamine or nitrogen oxides are formed as by-products in the reac-
tion. GC–MS analyses of the head space after the reaction of
phenylmethanamine 1a to form N-benzylidene phenylmethan-
amine using Au/TiO2 as a catalyst established the presence of
NH3 as the only nitrogenated compound. Although this analysis
does not exclude the presence of other nitrogen compound in the
liquid phase, the formation of ammonia strongly supports the fact
that oxidation occurs preferentially at the C atom bond bonded to
NH2. Since water is also detected in the vapour phase, the role of
oxygen is to bind hydrogen atoms that effect the oxidation and re-
sult in an unsaturated C@O or C@N bond.
amine by the aerobic oxidative condensation of benzylamine. It
would now be interesting to study if this very active catalyst can
be of general use to selectively oxidize a large number of benzyl-
amines and can also perform what would be very relevant catalyt-
ically, i.e., the oxidative cross condensation of benzylamines and
amines lacking hydrogens at the a-carbon.
3.1. Scope of the reaction
To show the generality of the catalyst a variety of substrates
have been aerobically oxidized. When benzylamines with para
substituents were reacted in the presence of Au/C (see Table 2
and Scheme 1), the corresponding N-benzylidene benzylamines
2b–c were obtained with high conversion and almost full selectiv-
ity. Though we have only three points, a fairly good linear relation-
ship between Hammett r
+ constant of the para substituent and the
initial reaction rate is observed (Fig. 5).
After this, the reactivity studies with phenylmethanamines
have been extended to other heterocyclic amines (Scheme 2). It
would be particularly interesting in the case of sulphur containing
reactants since the sulphur compounds can act as poisons of the
metal catalyst. However, taking into account that sulphur contain-
ing heterocycles are efficiently oxidized by gold nanoparticles [33],
it would be interesting to explore the oxidation of pyridyl and thi-
enylmethanamines. In the two cases, the amine was converted to
the corresponding N-arylidene amine with almost complete selec-
Pd and Pt nanoparticles supported on TiO2 particles are also ac-
tive in promoting the oxidation benzylamines, though their activ-
ity is lower than that of gold (see Table 2).
At this point, we have a gold catalyst (Au/C) that is extraordi-
narily active and selective for producing N-benzylidene benzyl-

142
A. Grirrane et al. / Journal of Catalysis 264 (2009) 138–144
Table 3
25
20
15
10
5
Conversion and selectivity towards N-arylidene arylmethanamines 5a–b for the
CH3
oxidation of heteroaryl amines 4a–b by oxygen in the presence of gold catalysts.
Reaction conditions: substrate, 1 mmol; toluene, 2 ml; oxygen pressure, 5 bar;
temperature, 373 K; and Au/substrate mol ratio, 1%.
H
Substrate Catalyst
Time
(min)
Product Conversion
(%)
Selectivity
(%)
Cl
4a
4b
4b
0.8% Au/C
0.8% Au/C
1.5% Au/TiO2
8
120
1800
5a
5b
5b
96
99
91
98
99
86
0
-0.2
-0.1
0
0.1
0.2
0.3
acetophenone 8a and acetophenone oxime 9a were also formed
in significant amounts (Scheme 3). In the oxidation of benzyl-
amine, benzaldehyde and benzaldehyde oxime are also detected
in trace quantities. Thus, although the products of the oxidation
of secondary amine 6a are similar to those observed for the oxida-
tion of benzylamine, their relative distribution is significantly
changed. We interpret the result of the lack of selectivity in the
oxidation of 1-phenylethanamine 6a as arising from the larger ste-
ric hindrance in the carbonyl group and amine due to the presence
Constante de Hammett
Fig. 5. Plot of the r0 vs. r+ for the oxidation of para-substituted phenylmethanam-
ines 1a–c catalyzed by Au/TiO2. Reaction conditions: benzylamine, 1 mmol;
toluene, 2 ml; oxygen pressure, 5 bar; temperature, 373 K; and Au/substrate mol
ratio, 1%.
N
N
N
O2/Toluene
Au catalyst
N
NH2
of a methyl group in the
zylamine. Due to the -methyl group, this steric hindrance disfa-
vours the spontaneous condensation of the aromatic ketone and
benzylamine. Also the presence of the -methyl favors oxidation
a-carbon as compared to the case of ben-
a
4a
5a
a
S
O2 /Toluene
Au catalyst
at this position with the final formation of the hydroxylamine.
The above-mentioned hypothesis is supported by the fact that
the oxidation of an even bulkier amine such as 1,1-diphenylme-
thanamine 6b forms benzophenone 8b as the prevalent product
accompanied with lesser amounts of N-(diphenylmethylidene) di-
phenyl methinime 7b (Scheme 3 and Table 4).
N
NH2
S
S
4b
5b
Scheme 2. Oxidation of heteroaryl amines to the corresponding N-arylidene
arylmethanamines.
Continuing with expanding the scope to different secondary
amines, Scheme 4 shows that dibenzylamine 10 undergoes dehy-
drogenation to compound 2a as well as C–N bond rupture to form
equivalent amounts of benzaldehyde 8c and benzaldehyde oxime
9c (Table 4). Recently, Baiker and co-workers have also studied this
transformation using Au(AcO)3 and Au(AcO)3 supported on ceria as
catalysts, and have reported high selectivity towards 2a [34].
Related tertiary tribenzylamine also reacts in the presence of
Au/TiO2 as catalyst, and N-benzylidene benzylamine 2a is
tivity (Table 3). Particularly remarkable is the case of the N-pyr-
idylmethanamine that is converted to the imine in less than
10 min under the conditions used. These heterocyclic imines are
interesting synthetic intermediates and ligands.
When Au/TiO2 was used as a catalyst for the oxidation of a
secondary amine such as 1-phenylethanamine 6a, besides the
expected N-(a-methyl)benzylidene 1-phenylethanamine 7a,
OH
R
R
R
O
N
NH2
O2/Toluene
Au/TiO2
N
+
+
R
R
7a,b
6a,b
8a,b
9a,b
R
a: CH3
b: Ph
c:
H
Scheme 3. Oxidation of secondary benzylamines 6a,b.
OH
H
O
N
O2/Toluene
Au/TiO2
N
H
N
H
+
+
10
2a
8c
9c
Scheme 4. Oxidation of dibenzylamine 10 catalyzed by Au/TiO2. Reaction conditions: dibenzylamine 10, 1 mmol; toluene, 2 ml; temperature, 373 K; catalyst, 1.5 wt% Au/
TiO2; Au/substrate, 1 mol%.

A. Grirrane et al. / Journal of Catalysis 264 (2009) 138–144
143
Table 4
Table 5
Conversion and selectivity towards secondary and tertiary benzylamines oxidation by
oxygen in the presence of gold catalysts. Reaction conditions: amine, 1 mmol;
toluene, 2 ml; oxygen pressure, 5 bar; temperature, 373 K; and Au/substrate mol
ratio, 1%.
Conversion (based on benzylamine) and selectivity for the oxidative cross conden-
sation of benzylamines and primary amines lacking -hydrogens by oxygen in the
presence of gold catalysts. Reaction conditions: benzylamine, 1 mmol; 12a,b,
1.5 mmol; toluene, 2 ml; oxygen pressure, 5 bar; temperature, 373 K; and Au/
substrate mol ratio, 1%.
a
Reactive
Catalyst
Time (h)
Product
Conversion (%)
Selectivity (%)
Substrates Catalyst
Time
(min)
Product Conversion
(%)
Selectivity
(%)
6b
10
11
0.8% Au/C
1.5% Au/TiO2
1.5% Au/TiO2
5
20
47
8b
2a
2a
100
100
55
92
70
54
4a + 12a
1c + 12aa
1c + 12a
1c + 12b
1b + 12b
1a + 12c
0.8% Au/C
1.5% Au/TiO2
0.8% Au/C
0.8% Au/C
0.8% Au/C
0.8% Au/C
0.5
21
21
16
12
13a
13b
13b
13c
13d
13e
100
98
100
100
100
100
99
41
99
99
99
99
O
H
O2/Toluene
Au/TiO2
18
N
N
+
a
Same reaction conditions using
chlorobenzylamine.
a 1:1 stoichiometry for p-toluidine vs. 4-
11
2a
8c
Scheme 5. Oxidation of tribenzylamine 11 catalyzed by Au/TiO2.
benzylamines was reversed and Au/C is notably more active than
Au/TiO2. Taking this into account, we could anticipate that the
reaction of a mixture of benzylamines and anilines with Au/C un-
der aerobic conditions could lead to the formation of N-arylidene
anilines.
accompanied by the formation of almost equivalent amounts of
benzaldehyde 8c. Probably both compounds are formed simulta-
neously in the same oxidative C–N bond rupture (Scheme 5).
3.2. Oxidative cross condensation of benzylamines and amines lacking
H in a-carbons
To test this cross condensation reaction, we have oxidized a
mixture of 2-pyridylmethanamine 4a, which can be rapidly trans-
formed in 5a and toluidine 12a (see Scheme 6). As expected, when
toluidine 12a was in 2 equivalents with respect to amine 4a and
when Au/C was used as a catalyst, the final product was the mixed
imine 13a with very high conversion and selectivity (Table 5). The
course of the reaction (Fig. 6) shows that compound 5a is a primary
and unstable product which under the reaction conditions converts
to the mixed imine 13a. Scheme 6 shows the observed product
intermediacy in the formation of compound 13a.
We have taken advantage of the remarkable influence of the
support on the catalytic activity of gold to design a selective cross
condensation process between benzylamines and anilines to form
N-benzylidene anilines. In a previous work, we have reported that
while Au/TiO2 promotes the oxidation of anilines to azobenzenes
efficiently, Au/C was inactive in catalyzing this process [13]. How-
ever, and as presented above, the reactivity for the oxidation of
N
Ar
O2/Toluene
O2/Toluene
Au catalyst
Ar
NH2
R
R
NH2
+
Ar
N
Ar
Au catalyst
H
4a (Ar = Py),
1a-c
12a: R = Ph-CH3
12b: R = tBu
12c: R = Ph
intermediate
13a-e
Ar
R
a: Py
C6H4CH3
b: C6H4Cl C6H4CH3
c: C6H4Cl tert-Bu
d: C6H4CH3 tert-Bu
e: C6H5
C6H5
Scheme 6. Oxidative cross condensation of benzylamines and primary amines lacking
a
-hydrogens.
100
75
50
25
0
100
75
50
25
0
0
5
10
15
20
25
30
35
0
5
10
15
20
-25
-25
Time (min)
Time (h)
Fig. 6. Plot of time conversion for the oxidation of 2-pyridylmethanamine 4a (j) in
the presence of 1.5 equivalents of toluidine 12a (ꢀ) to obtain N-aryl imine 13a (ꢂ)
and intermediate imine compounds 5a (M). Reaction conditions: compound, 4a
1 mmol; compound 12a, 2 mmol; toluene, 2 ml; oxygen pressure, 5 bar; temper-
ature, 100 °C; and catalysts, 0.8 wt% Au/C (Au/4a mol ratio, 1%).
Fig. 7. Plot of time conversion for the oxidation of 4-chlorobenzylamine 1c (j) in
the presence of 1.5 excess of tert-butylamine 12b (ꢀ) catalyzed by Au/C to obtain
imine compound 13c (ꢂ) and intermediate imine compound 2c (M). Reaction
conditions: 4-chlorobenzylamine, 1 mmol; tert-butylamine, 2 mmol; toluene, 2 ml;
temperature, 373 K; and catalyst Au/C, 1 mol%.

144
A. Grirrane et al. / Journal of Catalysis 264 (2009) 138–144
H2
Au/TiO2
NH2
O2
Au/TiO2
N
H
N
1a
2a
3a
Total 1a conversion 100 %
Selectivity towards 3a: 98 %
Scheme 7. One-catalyst, two-step process in which the intermediary imine formed is subsequently reduced to the secondary amine by hydrogen by the same gold catalyst
that effected the oxidation.
This concept of selective cross condensation was expanded to
the formation of other aryl imines. The results are shown in Table
5. The importance of using Au/C, which is an efficient catalyst for
benzylamines, is illustrated by the fact that with Au/TiO2 a mixture
of the N-aryl imine 13a and azobenzene is obtained. The formation
of azobenzene is derived from the homocoupling of aniline that oc-
curs in the presence of Au/TiO2 but not in the presence of Au/C
[13].
(3) That gold supported on titania is able to selectively catalyze
the formation of secondary benzylamines through a one-pot,
two-step reaction that involves one oxidative cross conden-
sation step followed by hydrogenation.
Acknowledgments
Besides N-substituted anilines, tertiary aliphatic amines can
also react on Au/C to produce the corresponding N-alkyl benzyli-
mine with high selectivity and yield. Table 5 illustrates the cross
condensation of tert-butylamine 12b and para-substituted benzyl-
amines 1b and 1c. Analogous to the case of 2-pyridylmethan-
amine 4a, the course of the reaction shows the formation of
compounds 2b and 2c as primary and unstable intermediates
for the formation of the final mixed imines 13d and 13c in high
yield (Fig. 7).
Financial support by the Spanish DGI (project CTQ2006-06958)
is gratefully acknowledged. A.G. also thanks CSIC for a research
associate contract.
Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jcat.2009.03.015.
References
3.3. Catalytic synthesis of secondary benzylamines through one-
catalyst, two-step process
[1] R.A. Sheldon, Catal. Oxid. (1995) 239.
[2] R.A. Sheldon, I.W.C.E. Arends, G.-J. Ten Brink, A. Dijksman, Acc. Chem. Res. 35
(2002) 774.
N-alkylation of amines is classically carried out through a SN2
mechanism using alkyl halides or aliphatic compounds having
good leaving groups [35]. However, this process suffers from a poor
selectivity since consecutive N-alkylation of the primary product
can lead to undesired by-products. An alternative process is the
reductive condensation of primary amines with carbonylic com-
pounds. Herein, considering the high product yield in benzylamine
oxidation and oxidative cross condensation as well as the fact that
gold catalysts can also catalyze the hydrogenation of C@N multiple
bonds [7], we envision a one-catalyst, two-step process in which
the initial imine formed in the cross condensation is subsequently
reduced to the secondary amine. If the proposed process would
take place with high efficiency and selectivity, it would be an inter-
esting general catalytic process for the formation of secondary
symmetric as well as asymmetric benzylamines. The process is
shown in Scheme 7.
[3] T. Mallat, A. Baiker (Eds.), Catalytic Oxidation for the Synthesis of Specialty and
Fine Chemicals, 2000 (in: Catal. Today 57 (1–2) (2000)).
[4] T. Mallat, A. Baiker, Chem. Rev. 104 (2004) 3037.
[5] A.S.K. Hashmi, G.J. Hutchings, Angew. Chem., Int. Ed. 45 (2006) 7896.
[6] S.A.K. Hashmi, Chem. Rev. 107 (2007) 3180.
[7] A. Corma, H. Garcia, Chem. Soc. Rev. 37 (2008) 2096.
[8] A. Corma, H. Garcia, in: D. Astruc (Ed.), Nanoparticles and Catalysis, Wiley and
Sons, Weinheim, 2008, p. 389.
[9] D.I. Enache, J.K. Edwards, P. Landon, B. Solsona-Espriu, A.F. Carley, A.A. Herzing,
M. Watanabe, C.J. Kiely, D.W. Knight, G.J. Hutchings, Science 311 (2006) 362.
[10] F. Minisci, F. Recupero, G.F. Pedulli, M. Lucarini, J. Mol. Catal. A 63 (2003) 204–
205.
[11] S.-I. Murahashi, Angew. Chem., Int. Ed. Engl. 34 (1995) 2443.
[12] S.I. Murahashi, N. Komiya, Catal. Today 41 (1998) 339.
[13] A. Grirrane, A. Corma, H. Garcia, Science 322 (2008) 1661.
[14] V.K. Aggarwal, D.M. Badine, V.A. Moorthie, Azirid. Epox. Org. Synth. (2006) 1.
[15] V.I. Tararov, A. Boerner, Synlett (2005) 203.
[16] H. Miyabe, M. Ueda, T. Naito, Synlett (2004) 1140.
[17] C. Palomo, J.M. Aizpurua, I. Ganboa, M. Oiarbide, Eur. J. Org. Chem. (1999)
3223.
[18] D. Enders, U. Reinhold, Tetrahedron Asym. 8 (1997) 1895.
[19] J. Gawronski, N. Wascinska, J. Gajewy, Chem. Rev. 108 (2008) 5227.
[20] S.J. Connon, Angew. Chem., Int. Ed. 47 (2008) 1176.
[21] G.K. Friestad, A.K. Mathies, Tetrahedron 63 (2007) 2541.
[22] R.A. Sheldon, Pure Appl. Chem. 72 (2000) 1233.
[23] R.J. Angelici, J. Organomet. Chem. 693 (2008) 847.
[24] B. Zhu, M. Lazar, B.G. Trewyn, R.J. Angelici, J. Catal. 260 (2008) 1.
[25] J.W. Geus, J.A.R. van Veen, Catalysis: An Integrated Approach, second ed., vol.
123, 1999, p. 459.
As anticipated based on the catalytic activity of supported gold
nanoparticles we have been able to obtain different secondary
amines in one-pot, two-step reactions with the same catalyst start-
ing from benzylamine 1a.
4. Conclusions
[26] M. Haruta, Gold Bull. 37 (2004) 27.
[27] W.C. Li, M. Comotti, F. Schuth, J. Catal. 237 (2006) 190.
[28] G. Smit, Kem. Ind. 54 (2005) 389.
We have found the following:
[29] L. Prati, G. Martra, Gold Bull. 32 (1999) 96.
[30] W.G. Council, Gold Bull. (2003) 3624.
[31] Z. Chen, Q. Gao, Appl. Catal. B 84 (2008) 790.
[32] M. Manzoli, A. Chiorino, F. Boccuzzi, Stud. Surf. Sci. Catal. 155 (2005) 405.
[33] A. Abad, A. Corma, H. Garcia, Chem. Eur. J. 14 (2008) 212.
[34] L. Aschwanden, T. Mallat, J.-D. Grunwaldt, A. Baiker, J. Mol. Catal. A Chem 300
(1–2) (2009) 111.
[35] J. March, Advanced Organic Chemistry: Reactions, Mechanisms and Structures,
third ed., McGraw Hill, New York, 1993.
(1) That the oxidation of amines to benzylidene amines on gold
is
a structure sensitive reaction that requires smaller
crystallites.
(2) That gold supported on carbon selectively catalyzes full oxi-
dative cross condensation of benzylamines and amines. Oxi-
dative condensation also occurs efficient and selectively
with heterocyclic amines containing sulphur.