Efficient tandem synthesis of methyl esters and imines by using versatile hydrotalcite-supported gold nanoparticles

Article abstract of DOI:10.1002/chem.201202077

Efficient basic hydrotalcite (HT)-supported gold nanoparticle (AuNP) catalysts have been developed for the aerobic oxidative tandem synthesis of methyl esters and imines from primary alcohols catalyzed under mild and soluble-base-free conditions. The catalytic performance can be fine-tuned for these cascade reactions by simple adjustment of the Mg/Al atomic ratio of the HT support. The one-pot synthesis of methyl esters benefits from high basicity (Mg/Al=5), whereas moderate basicity greatly improves imine selectivity (Mg/Al=2). These catalysts outperform previously reported AuNP catalysts by far. Kinetic studies show a cooperative enhancement between AuNP and the surface basic sites, which not only benefits the oxidation of the starting alcohol but also the subsequent steps of the tandem reactions. To the best of our knowledge, this is the first time that straightforward control of the composition of the support has been shown to yield optimum AuNP catalysts for different tandem reactions. Copyright

Full text of DOI:10.1002/chem.201202077

FULL PAPER
DOI: 10.1002/chem.201202077
Efficient Tandem Synthesis of Methyl Esters and Imines by Using Versatile
Hydrotalcite-Supported Gold Nanoparticles
[
a]
[b]
[a]
Peng Liu, Can Li, and Emiel J. M. Hensen*
Abstract: Efficient basic hydrotalcite
synthesis of methyl esters benefits from
high basicity (Mg/Al=5), whereas
moderate basicity greatly improves
imine selectivity (Mg/Al=2). These
catalysts outperform previously report-
ed AuNP catalysts by far. Kinetic stud-
ies show a cooperative enhancement
between AuNP and the surface basic
sites, which not only benefits the oxida-
tion of the starting alcohol but also the
subsequent steps of the tandem reac-
tions. To the best of our knowledge,
this is the first time that straightfor-
ward control of the composition of the
support has been shown to yield opti-
mum AuNP catalysts for different
tandem reactions.
(
(
HT)-supported
AuNP) catalysts have been developed
gold
nanoparticle
for the aerobic oxidative tandem syn-
thesis of methyl esters and imines from
primary alcohols catalyzed under mild
and soluble-base-free conditions. The
catalytic performance can be fine-
tuned for these cascade reactions by
simple adjustment of the Mg/Al atomic
ratio of the HT support. The one-pot
Keywords: gold
catalysis supported catalysts
oxidation · oxygen
·
heterogeneous
·
·
Introduction
though this approach avoids the use of corrosive carboxylic
[5]
acids or activated carboxylic acid derivatives, supported
gold catalysts commonly require the use of base additives
(e.g., K CO or NaOCH ) and harsh conditions (elevated
The concept of tandem catalysis is very promising for carry-
ing out cascade reactions in one reactor and thereby im-
proving the efficiency of chemical synthesis in terms of
energy consumption and waste formation. Compared with
the homogeneous complexes commonly used in metal-cata-
lyzed tandem reactions, the use of heterogeneous catalysts
would offer significant advantages such as higher stability,
reduced contamination of the product, and, perhaps most
2
3
3
temperature and 3–20 bar O ) to achieve high yields of
2
[
1]
methyl esters. Without base additives, acetals can be ob-
[
4g,j]
tained as a main byproduct.
dative coupling of alcohols and amines to obtain industrially
Another example is the oxi-
[6]
valuable imines. This tandem reaction was also performed
[6e]
[6f]
using Au/hydroxyapatite
and Au/TiO2
catalysts, al-
[
2]
importantly, facile catalyst separation and reuse. However,
examples of highly selective heterogeneous catalysts for cas-
though in the latter case only moderate imine yields were
obtained, even in the presence of a base additive. The rate-
controlling step in these two reactions has been suggested to
be the oxidation of the alcohol, explaining the need for
[3]
cade reactions are scarce.
Recently, interest has been growing in the application of
supported gold nanoparticle (AuNP) catalysts in tandem
[7]
bases. From a green chemistry point of view, it is an attrac-
tive and challenging goal to develop multifunctional cata-
lysts that combine AuNP with a solid base support that can
perform such desirable tandem syntheses of methyl esters
and imines under milder (ideally atmospheric pressure) and
base-additive-free conditions.
[3]
synthesis reactions. Supported AuNP were demonstrated
to be efficient catalysts for the one-step oxidative esterifica-
tion of primary alcohols with methanol to methyl esters
[4]
using molecular oxygen. A wide variety of materials have
[4a]
[4b–f]
been explored to support AuNP such as Al O , TiO ,
2
3
2
[4n]
[4f–h]
[4i]
[4j]
[4k–m]
CeO2,
MOF, Ga O , SiO2,
and polymers. Al-
Hydrotalcite (HT: Mg Al (OH) CO ·nH O) type layered
2
3
6
2
16
3
2
double hydroxides are known to possess surface basic prop-
[8]
erties that can be fine-tuned by their composition. It has
been demonstrated that HT is a promising support material
[
a] Dr. P. Liu, Prof. Dr. E. J. M. Hensen
Department of Chemical Engineering and Chemistry
Eindhoven University of Technology
P.O. Box 513, Eindhoven (The Netherlands)
Fax : (+31)40-245-5054
[9]
[10]
for AuNP in the catalytic oxidation, dehydrogenation,
[11]
and deoxygenation of organic chemicals. However, the ef-
fects of HT composition on the size of AuNP and the cata-
lytic performance are still unknown. We have recently re-
ported on the benefit of doping transition-metal cations into
HT to render excellent AuNP catalysts for the aerobic oxi-
E-mail: e.j.m.hensen@tue.nl
[
b] Prof. Dr. C. Li
State Key Laboratory of Catalysis
Dalian Institute of Chemical Physics
Chinese Academy of Sciences
[
12]
dation of alcohols.
A strong synergistic effect between
III
AuNPs and Cr -containing HT supports was found to be re-
lated to the Cr cation–AuNP interactions, which enhance
the alcohol dehydrogenation activity.
4
57 Zhongshan Road, Dalian 116023 (P.R. China)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201202077.
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Herein, we will show that Au/HT catalysts exhibit excel-
lent performance in the aerobic oxidative tandem synthesis
of methyl esters and imines with selectivity up to 100%
(Figure 2). The surface area, mean Au particle size, Au load-
ing, and basicity of the various catalysts are collected in
Table 1. Evidently, an increase in the Mg/Al atomic ratio of
the HT from 2 to 6 led to an increase of the support basicity,
and to a decrease of the HT surface area and also to gold
under atmospheric O pressure and soluble-base-free condi-
2
tions. Their performance can be tailored for a specific
tandem synthesis by simple ad-
justment of the basicity of the
Table 1. Textural, chemical, and catalytic benzyl alcohol oxidation properties of various supported Au cata-
lysts.
HT support by variation of the
Mg/Al atomic ratio. To the best
of our knowledge, this is the
first time that straightforward
control of the composition of
the support has been shown to
yield optimum AuNP catalysts
for different tandem reactions.
These Au/HT catalysts exhibit
superior catalytic performance
for tandem synthesis of methyl
esters and imines in terms of
activity, selectivity, workup pro-
Catalyst
S
BET
2
d
[nm]
Au
Au
[wt%]
Basicity
[pH]
Yield
[%]
Sel.
[%]
À1
[a]
[b]
[c]
[c]
A[ m g
H
U
G
R
N
U
]
A
H
U
T
E
N
N
1
2
3
4
5
6
7
8
9
Au/Mg
Au/Mg
2
Al-HT
Al-HT
103
97
62
53
16
50
72
212
225
2.1
2.2
2.6
2.7
2.8
2.2
2.3
3.0
3.3
0.42
0.41
0.38
0.37
0.29
0.98
0.90
0.85
0.94
8.5
8.8
9.2
9.4
9.6
5.8
7.1
6.7
6.5
60
72
65
53
28
6
25
10
12
>99
>99
>99
99
3
Au/Mg Al-HT
4
Au/Mg
Au/Mg
5
Al-HT
Al-HT
6
98
Au/TiO
2
>99
>99
>99
>99
Au/HAP
Au/g-Al
Au/Ga Al
2
O
3
3
3
O
9
cedure, and milder conditions [a] Determined by ICP-OES. [b] By suspension of catalyst (10 mg) in distilled water (3 mL). [c] Yield and se-
compared with state of the art lectivity of benzaldehyde [reaction conditions: benzyl alcohol (0.5 mmol), n-dodecane (0.1 mmol), and Au cat-
À1
[4a–n,6a–f]
alyst (0.5 mol%) in toluene (10 mL), O (20 mLmin ), 333 K, 1 h] were determined by GC-MS and GC-FID
analyses.
techniques.
2
Results and Discussion
loading. These changes were accompanied by a slight in-
crease in the particle size from 2.1 to 2.8 nm. These data
A set of Mg Al-HT (x=2, 3, 4, 5, and 6) supports was pre-
show how the texture and nature of the support influence
AuNP size.
x
[8a]
pared by a coprecipitation method. The well-defined lay-
ered structure characteristic of hydrotalcites was confirmed
To obtain further insights into the gold–support interac-
tions, we compared the temperature-programmed surface
2
7
by XRD analysis. The Al MAS NMR spectra of all sup-
ports show that Al predominantly occupies octahedral sites
[12]
reaction (TPSR) of preadsorbed isopropanol
on Mg Al-
x
[13]
(
d=9.6 ppm). Au/Mg Al-HT catalysts were prepared by a
HT and Au/Mg Al-HT samples (Figure 3). It can be clearly
x
x
modified deposition/precipitation method using NaBH to
seen that the dehydrogenation activity strongly increases
with increasing Mg/Al ratio, which is attributed to the corre-
sponding increase in basiciy. The somewhat smaller peak
4
[12]
reduce the gold precursor.
Introduction of gold did not
change the structure of the support (Figure 1). TEM analysis
of the Au/Mg Al-HT catalysts revealed highly dispersed
area of the H evolution peak for the more basic supports is
x
2
gold particles with average diameters of less than 3.0 nm
mainly due to the lower gold loading.
Initially, we investigated the influence of the Mg/Al ratio
on the catalytic activity of Au/Mg Al-HT in the liquid-phase
x
aerobic oxidation of benzyl alcohol (BA). The oxidation of
BA was performed in toluene under atmospheric O2 at
3
(
9
33 K for 1 h; the results are listed in Table 1. Benzaldehyde
BD) was the predominant product (selectivity more than
8%) in all cases. The parent HT supports did not convert
BA under identical conditions. The maximum BD yield was
observed for the catalyst with Mg/Al=3, which indicates
that the specific nature of the HT support has a strong influ-
ence on the catalytic activity of the AuNP. Au/Mg Al-HT
x
catalysts substantially outperform other commonly used
oxide-supported Au catalysts (Au/TiO2, Au/Al O , Au/
2
3
Ga Al O , and Au/HAP; HAP=hydroxylapatite). The
3
3
9
strong basicity of the surface plays a role in the alcohol acti-
[9,12,14]
vation.
The activity decrease at higher Mg/Al ratio is
2
7
mainly due to the lower HT surface area (Table 1, entry 5).
These promising catalysts were then evaluated for their
activity in tandem synthesis reactions, that is, oxidative es-
Figure 1. XRD patterns (A) and Al MAS NMR spectra (B) of a) Au/
Mg Al-HT; b) Au/Mg Al-HT; c) Au/Mg Al-HT; d) Au/Mg Al-HT, and
e) Au/Mg Al-HT.
2
3
4
5
6
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Synthesis of Methyl Esters and Imines
FULL PAPER
Figure 2. TEM images and Au particle size distributions for a) Au/Mg
HT.
2 3 4 5 6
Al-HT; b) Au/Mg Al-HT; c) Au/Mg Al-HT; d) Au/Mg Al-HT, and e) Au/Mg Al-
Table 2. One-pot oxidative esterification of benzyl alcohol in the pres-
[
a]
ence of methanol over various supported Au catalysts.
Catalyst
Conv.
%]
Selectivity [%]
[
Aldehyde
Ester
1
2
3
4
5
6
7
8
9
1
Au/Mg
Au/Mg
Au/Mg
Au/Mg
Au/Mg
2
3
4
5
6
Al-HT
Al-HT
Al-HT
Al-HT
Al-HT
43
64
91
98
77
5
15
8
11
94
33
17
3
<1
12
81
41
84
78
3
67
83
97
>99
88
18
58
15
21
97
Au/TiO
2
Au/HAP
Au/g-Al
Au/Ga Al
Au/Mg
2
O
3
3
3
O
9
[
b]
0
5
Al-HT
Figure 3. H
catalysts: a) Au/Mg
Mg Al-HT, and e) Au/Mg
2
evolution of isopropanol during TPSR for Au/Mg
Al-HT; b) Au/Mg Al-HT; c) Au/Mg Al-HT; d) Au/
Al-HT. The dashed line is the result of the cor-
x
Al-HT
[
a] Reaction conditions: benzyl alcohol (0.5 mmol), n-dodecane
2
3
4
(
(
0.1 mmol), and Au catalyst (0.5 mol%) in methanol (10 mL),
10 mLmin ), 333 K, 3 h; conversion and selectivity were determined by
O
2
5
6
À1
responding HT without gold.
GC-MS and GC-FID analysis. [b] Results for the third run.
terification to form methyl esters and oxidative tandem syn-
thesis of imines. The oxidative esterification of BA was car-
eral, both the activity and the ester selectivity of the Au/
ried out in methanol at 333 K under atmospheric O for 3 h
Mg Al-HT catalysts increase with the Mg/Al ratio. Only the
2
x
(
Table 2). In addition to BD and methyl benzoate, no by-
performance of Au/Mg Al-HT was lower, which is probably
6
products such as acid or acetal were formed on the Au/
related to its lower activity in alcohol oxidation. This
tandem reaction occurs in three steps (Scheme 1): 1) alcohol
oxidation to the aldehyde, 2) hemiacetal formation by con-
densation (the hemiacetal was not observed by GC-MS),
Mg Al-HT catalysts. To our delight, we found that Au/
x
Mg Al-HT catalyst could almost quantitatively convert BA
5
into methyl benzoate under mild reaction conditions. In gen-
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E. J. M. Hensen et al.
oxide supports have been implicated in hemiacetal forma-
[4i,j,15]
tion, leading to further formation of the acetal.
We also found that the Au/Mg Al-HT catalyst is very effi-
5
Scheme 1. Mechanism for Au/Mg
terification.
x
Al-HT-catalyzed tandem oxidative es-
cient for the oxidative esterification of various primary alco-
hols (including benzylic, allylic, and aliphatic alcohols)
under similar mild conditions, achieving excellent selectivity
(
up to 100%) of methyl esters (Table 3). Moreover, the Au/
Table 3. One-pot oxidative esterification of various primary alcohols in
5
[a]
the presence of methanol over Au/Mg Al-HT catalyst.
Substrate
t
[
Conv.
[%]
Selectivity [%]
h]
Aldehyde
Ester
1
2
3
4
5
6
7
8
4-methoxybenzyl alcohol
4-methylbenzyl alcohol
4-chlorobenzyl alcohol
4-nitrobenzyl alcohol
cinnamyl alcohol
1-octanol
3
3
5
6
5
10
0.5
0.5
100
100
>99
54
100
51
0
0
<1
2
0
0
100
100
>99
98
100
100
65
benzyl alcohol
benzyl alcohol
34
42
35
31
[
b]
69
[
a] Reaction conditions: substrate (0.5 mmol), n-dodecane (0.1 mmol),
À1
and Au/Mg
5
Al-HT (0.5 mol%) in methanol (10 mL), O
2
(10 mLmin ),
3
33 K. [b] Substrate (1.0 mmol), n-dodecane (0.2 mmol), and Au/Mg
5
Al-
À1
2
HT (0.5 mol%) in methanol (10 mL), O (10 mLmin ), 333 K.
Mg Al-HT catalyst could be readily recovered and reused
5
without significant loss of performance (Table 2, entry 10).
For the recycled catalyst, TEM and elemental analysis did
not indicate AuNP aggregation or metal leaching. Bearing
in mind that previously reported supported AuNP catalysts
typically require base additives, elevated temperature and
Figure 4. Reagents and conditions: benzyl alcohol (BA, 0.5 mmol) or
benzaldehyde (BD, 0.5 mmol), n-dodecane (0.1 mmol), and Au/Mg
5
Al-
À1
HT (0.5 mol%) in methanol (10 mL), O
2
(10 mLmin ), 333 K. (A) Re-
action profile of oxidative esterification of BA (*) to methyl benzoate
~) via BD (&); (A, inset) plot of first-order rate equation for consump-
(
tion of BA. (B) Reaction profile of oxidative esterification of BD to
methyl benzoate; (B, inset) plot of first-order rate equation for consump-
tion of BD.
higher O pressure (3–20 bar) to obtain high yield of es-
2
[
4b,d–m]
[4c]
ters,
and only Au/K Ti O
13
and polymer-incarcerated
2
6
[4n]
gold catalyst (PI-Au) were reported to be effective at an
O pressure of 1 bar and basic conditions, the Au/Mg Al-HT
2
5
[4]
and 3) further oxidation to form the methyl ester. A kinet-
catalyst described here is indeed the most environmentally
benign and efficient catalysts reported so far for the tandem
synthesis of methyl esters.
ic study to establish the most active Au/Mg Al-HT catalyst
5
using BA and BD as reactants (Figure 4) demonstrated that
the first step is first order in alcohol consumption and that
the integrated reaction rate of the subsequent steps (2+3) is
about five times faster than that of step 1. This confirms that
Encouraged by this result, we also evaluated the applica-
bility of Au/Mg Al-HT catalysts for the oxidative tandem
x
synthesis of imines. For this purpose, we used BA and 1-hex-
ylamine as model substrates (Table 4). Interestingly, Au/
[4c,g,j,n]
BA oxidation is the rate-controlling step.
Although the
alcohol oxidation activity of Au/Mg Al-HT is lower than
Mg Al-HT showed the best catalytic performance, with
5
2
that of Au/Mg Al-HT, its performance in oxidative esterifi-
imine selectivity up to 97%. The results show that, as a
function of the Mg/Al ratio, BA conversion exhibits an opti-
mum, as observed for BA oxidation. However, the imine se-
3
cation is much better because of the higher basicity and
higher alcohol dehydrogenation activity. On the basis of
these observations, a delicate cooperation between AuNP
lectivity decreased for the more basic samples. Au/Mg Al-
5
and the basic sites of Mg Al-HT may be suggested, which
HT and Au/Mg Al-HT gave very low imine selectivities and
5
6
not only benefits the oxidation of the starting alcohol but
also the subsequent base-promoted steps of the tandem re-
action, including formation of the hemiacetal as an inter-
mediate and its further oxidation. This speculation is sup-
ported by the observation that the latter step was strongly
inhibited when the AuNPs were supported on less basic ma-
terials (Table 2, entries 6–9). Previously, Lewis acidic sites of
BD was the main product in these cases (Table 4, entries 4
and 5). Conversely, the gold reference catalysts gave imine
as the main product, but only at low BA conversion
(Table 4, entries 6–9). It is noteworthy that Au/Mg Al-HT
2
shows a much better catalytic performance than previously
[6e]
[6f]
reported Au/HAP
and Au/TiO2
catalysts under the
same conditions (Table 4, entries 6 and 7).
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Synthesis of Methyl Esters and Imines
FULL PAPER
Table 4. Tandem synthesis of imine by oxidative coupling of 1-hexyl-
[
a]
amine and benzyl alcohol over various supported Au catalysts.
Catalyst
Conv.
%]
Selectivity [%]
[
Aldehyde
Imine
1
2
3
4
5
6
7
8
9
1
Au/Mg
Au/Mg
Au/Mg
Au/Mg
Au/Mg
2
3
4
5
6
Al-HT
Al-HT
Al-HT
Al-HT
Al-HT
95
98
82
46
22
11
32
16
13
91
3
10
32
78
89
17
5
18
23
7
97
90
68
22
11
83
95
82
77
93
Au/TiO
2
Au/HAP
Au/g-Al
Au/Ga Al
Au/Mg
2
O
3
3
3
O
9
[
b]
0
2
Al-HT
[
a] Reaction conditions: benzyl alcohol (0.5 mmol), 1-hexylamine
(
0.5 mmol), n-dodecane (0.1 mmol), and Au catalyst (0.5 mol%) in tol-
À1
uene (10 mL), O
2
(20 mLmin ), 333 K, 5 h; conversion of benzyl alcohol
and selectivity were determined by GC-MS and GC-FID analysis. [b] Re-
sults for the third run.
In an attempt to understand the reaction mechanism, our
kinetic analysis using BA and BD was extended to the
imine synthesis for Au/Mg Al-HT (Figure 5). Notably, the
2
condensation of BD and 1-hexylamine under atmospheric
O was about four times faster than without O , and also
2
2
faster than the oxidative coupling of BA and amine. This in-
dicates that BA oxidation remains the rate-controlling step
and oxygen also plays an important role in the condensation
step. Surprisingly, a small amount of BA was observed for
both condensation reactions. Without the amine, the reverse
reaction did not occur. We also investigated whether BA
was formed in the condensation reaction between BD and
1
-hexylamine for the parent Mg Al-HT supports (Table S1
x
in the Supporting Information). No BA was observed for
Mg/Al=2 and 3, but its formation was evident for higher
ratios. We conclude from this that the AuNPs and strong
basic sites are necessary for BA formation. Based on these
Figure 5. Reagents and conditions: benzyl alcohol (BA, 0.5 mmol) or
benzaldehyde (BD, 0.5 mmol), 1-hexylamine (0.5 mmol), n-dodecane
(
0.1 mmol), and Au/Mg
2
Al-HT (0.5 mol%) in toluene (10 mL),
O
2
À1
(20 mLmin ), 333 K. (A) Reaction profile of oxidative coupling of BA
(
*) and 1-hexylamine to benzyl imine (~) via BD (&); (A, inset) plot
observations, a plausible mechanism for Au/Mg Al-HT-cata-
x
of first-order rate equation for consumption of BA. (B) Reaction profile
of condensation of BD and 1-hexylamine to benzyl imine in the presence
lyzed tandem oxidative coupling of primary alcohols and
amines is illustrated in Scheme 2. The rate-controlling oxida-
of O
2
; (B, inset) plot of first-order rate equation for consumption of BD.
(
C) Reaction profile of direct condensation of BD and 1-hexylamine to
benzyl imine in the absence of O
tion for consumption of BD.
2
; (C, inset) plot of first-order rate equa-
[7c]
acid sites to facilitate the condensation step, in contrast to
the earlier supposition of the importance of support acidi-
[
6b,d,e]
ty.
strongly inhibited. This is in line with the result obtained for
When the support basicity is too high, Step 2 can be
x
Scheme 2. A proposed mechanism for Au/Mg Al-HT-catalyzed tandem
oxidative coupling of primary alcohols and amines.
[6e]
MgO-impregnated Au/HAP catalyst.
that the adsorbed oxygen on Au surfaces and the strong
We further infer
[16]
tion of alcohol occurs on Au/HT catalysts through basic site-
promoted proton abstraction to form aldehyde (Step 1).
Step 2 is the fast transformation of the aldehyde with the
amine over Au/HT in the presence of oxygen to form the
imine. We surmise that cationic gold species act as Lewis
basic sites on HT can activate the NÀH bond of the amine.
The H atom will react with the aldehyde to regenerate the
alcohol. In the case of Au/Mg Al-HT, the rate of the con-
2
densation step is significantly increased and the reversible
transfer hydrogenation is strongly suppressed. This is proba-
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E. J. M. Hensen et al.
bly the result of a delicate acid/base balance between sur-
a very promising 90% imine yield with 100% imine selectiv-
ity was achieved by using only 0.08 mol% catalyst with BA
and 1-hexylamine as substrates (Table 5, entry 10).
face gold cations and the Mg Al-HT support.
2
The Au/Mg Al-HT catalyst could be reused without sig-
2
nificant loss of performance (Table 4, entry 10). To establish
To further underpin the superior activities of our Au/
the substrate scope, Au/Mg Al-HT was also applied for the
Mg Al-HT catalysts compared with previously reported
2
x
tandem synthesis of imines from a variety of alcohols and
amines (Table 5). Various kinds of alcohols (including aro-
matic and allylic alcohols) and amines (including aromatic
AuNP catalysts, it would be best to compare the turnover
frequencies (TOF). However, most studies use quite differ-
ent reaction conditions; therefore, we prepared and com-
pared several representative reference AuNP catalysts
under our mild conditions (Tables S2 and S3 in the Support-
Table 5. Tandem oxidative coupling of various primary alcohols and
[
a]
ing Information). Au/Ga Al O has been reported to achieve
3 3 9
amines over Au/Mg
2
Al-HT catalyst.
À1
high activity (TOF=141 h ) as Au/Ga O catalyst in the ox-
2
3
idative esterification of BA under 5 bar O at 363 K, with
2
[4j]
8
5% ester selectivity and 4.2% acetal yield. Under our
Substrate
t
[
Conv.
[%]
Selectivity [%]
[
b]
milder conditions (1 bar O at 333 K) this catalyst exhibited
a TOF of only 1.5 h with 21% ester selectivity, which is
significantly lower than the TOF of 65 h for our optimized
Au/Mg Al-HT catalyst (with over 99% ester selectivity). To
our delight, the Au/Mg Al-HT catalyst can also achieve very
high activity (TOF=238 h ) under 3 bar O at 373 K with
h]
2
1
2
À1
R
R
Aldehyde
Imine
À1
1
2
3
4
5
6
7
8
9
1
4-CH
4-CH
3
O-C
-C
6
H
4
n-C
n-C
n-C
n-C
n-C
n-C
6
6
6
6
6
4
H
H
H
H
H
H
13
13
13
13
13
5
5
100
97
77
0
18
5
100
82
95
3
6
H
4
5
4-Cl-C
4-NO -C
-CH=CH
6
H
4
10
12
10
5
5
2
6
H
4
88
<1
0
37
3
>99
100
63
À1
2
C
C
C
C
C
C
6
6
6
6
6
6
H
H
H
H
H
H
5
5
5
5
5
5
100
96
96
46
59
90
9
8% ester selectivity and no acetal formation. Under these
9
C
6
H
5
-CH
2
6
1
1
97
identical conditions, Au/TiO2 and Au/Ga Al O catalysts
showed much lower activity (TOF=18 and 25 h , respec-
tively) with the formation of acetal (ca. 5% selectivity).
From the comparison, it is clear that the Au/Mg Al-HT cata-
lyst can suppress the formation of acetal byproducts, and
previous optimal Au/TiO2 and Au/Ga Al O catalysts are
3
3
9
À1
n-C
n-C
n-C
6
H
6
H
6
H
13
13
13
63
56
0
37
44
100
[
c]
[
d]
0
10
5
[
a] Reaction conditions: alcohol (0.5 mmol), amine (0.5 mmol), n-dodec-
ane (0.1 mmol), and Au/Mg
20 mLmin ), 333 K. [b] Conversions based on alcohol. [c] Benzyl alco-
2
Al-HT (0.5 mol%) in toluene (10 mL), O
2
À1
3
3
9
(
hol (1.0 mmol), 1-hexylamine (1.0 mmol), n-dodecane (0.2 mmol), and
not effective under 1 bar O and mild temperature. Only
2
À1
[4c]
[4n]
Au/Mg
2
Al-HT (0.5 mol%) in toluene (10 mL), O
2
(20 mLmin ), 333 K.
Au/K Ti O
13
and Au/Polymer were previously shown to
2
6
[
(
3
d] Benzyl alcohol (10.0 mmol), 1-hexylamine (10.0 mmol), n-dodecane
be useful catalysts for methyl ester synthesis under 1 bar O2.
Without base additive, Au/K Ti O exhibits a TOF of only
À1
1.0 mmol), Au/Mg
73 K.
2 2
Al-HT (0.08 mol%), solvent-free, O (20 mLmin ),
2
6
13
À1
2
.7 h , whereas the activity of Au/Polymer in the presence
of a soluble base has a TOF of only approximately 4.2 h .
Thus, for one-pot synthesis of methyl esters under 1 bar O2
À1
and aliphatic amines) could be converted into the corre-
sponding imines in high yields. Although several other het-
erogeneous catalysts, such as Mn-containing octahedral mo-
and soluble-base-free conditions, the Au/Mg Al-HT catalyst
5
shows about one order of magnitude higher activity than the
state of the art AuNP catalysts. Similarly, for tandem synthe-
sis of imines under mild and base-additive-free conditions,
[
6b]
[6c]
lecular sieves, Ru hydroxide supported on TiO2, and Pd
[6d]
nanoparticles supported on boehmite nanofibers,
have
been reported to be efficient for this tandem alcohol oxida-
tion/imine formation reaction, these systems require an
excess of amines, relatively high temperatures (above
the Au/Mg Al-HT catalyst has a substantially higher activity
than the previously reported preferred Au/HAP and Au/
2
TiO catalysts.
2
3
63 K), and long reaction times. Significantly, Au/Mg Al-HT
2
is the most active heterogeneous catalysts for the oxidative
tandem synthesis of imines working under mild conditions
without the need for soluble bases. Because stoichiometric
amounts of both alcohol and amine can be used, the product
workup is simplified.
It is noteworthy that higher substrate concentration did
not adversely affect the catalytic performance. We carried
out aerobic BA oxidation at twice the initial BA concentra-
Conclusion
We have shown that the Mg/Al atomic ratio of hydrotalcite
strongly affects the catalytic performance of supported gold
nanoparticles for aerobic alcohol oxidation, the one-pot oxi-
dative esterification of alcohols to methyl esters, and the
tandem oxidative coupling of alcohols and amines to imines.
The tunability of the base properties makes hydrotalcites
ideal supports for optimal gold catalysts for green organic
synthesis under mild and base-additive-free conditions. Our
protocol for tandem synthesis offers considerable advantag-
es over previously reported approaches, including milder re-
action conditions, simpler workup procedure, significantly
higher activity, and reusability of the catalysts with retention
tion and found that the BD yield increased for Au/Mg Al-
3
HT from 72 to 86%. Similarly, for tandem syntheses of
model methyl ester and imine reactions, higher initial sub-
strate concentrations led to higher reaction rates and higher
product yields (Table 3, entries 7 and 8; Table 5, entries 8
and 9). The potential of the Au/Mg Al-HT catalyst is further
2
underpinned by the results for solvent-free imine synthesis;
&
6
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Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Synthesis of Methyl Esters and Imines
FULL PAPER
of catalytic efficiency. We believe that the results presented
herein widen the avenue for the application of supported
gold catalysts to green and tandem organic synthesis.
charged with alcohol (0.5 mmol), amine (0.5 mmol), Au catalyst
(
(
(
0.5 mol%), n-dodecane (0.1 mmol, internal standard), and toluene
10 mL). Molecular oxygen was bubbled through the reaction mixture
À1
flow rate 20 mLmin ). The resulting mixture was then heated at 333 K
for 5 h. For both cases, after the reaction, the catalyst was separated by
centrifugation and washed with acetone. After drying at RT in vacuo, the
recycled catalyst can be reused in the next run under the same conditions.
The reaction products were qualitatively analyzed by GC-MS and quanti-
tatively analyzed by GC-FID using an internal standard technique. In all
cases, the carbon balances were 100Æ2%.
Experimental Section
Catalyst preparation: The various hydrotalcite supports, Mg
x
Al-HT (x=
/Al(NO
x
Al-HT cata-
2
, 3, 4, 5 and 6), were prepared by coprecipitation of Mg
A
H
U
T
E
N
N
3
)
2
A
T
N
T
E
N
N
3 3
)
[
8a]
and NaOH/Na
2
CO
3
[
12]
lysts were prepared by a sequential deposition/reduction approach. As
an example, Mg Al-HT (1.0 g) was suspended in an aqueous solution of
HAuCl (1 mm, 50 mL, theoretical Au loading is 1.0 wt%). After stirring
3
4
for 2 min, aqueous NaOH (0.5m) was added to adjust the pH to approxi-
mately 9.0, and the resulting mixture was stirred at RT for 12 h. This
slurry was filtered, washed with deionized water, and dried at RT in
Acknowledgements
This research was financially supported by Programme Strategic Scientif-
ic Alliances between the Netherlands and China (Grant No. 2008DFB5–
30) funded by the Royal Netherlands Academy of Arts and Science and
the Chinese Ministry of Science and Technology. We thank the Soft
Matter Cryo-TEM Research Unit of Eindhoven University of Technolo-
gy for access to TEM facilities.
vacuo. The solid was subsequently treated with aqueous NaBH
fold excess) solution at RT for 2 h, then filtered, washed, and dried to
yield Au/Mg Al-HT. Reference catalysts Au/TiO Au/g-Al Au/
and Au/HAP were prepared by the homogeneous deposi-
tion/precipitation method using urea as the precipitation agent, as devel-
4
(three-
1
3
2
,
2 3
O ,
[
17]
[6e]
3 3 9
Ga Al O ,
[
18]
oped by Louis et al., and the theoretical Au loading was 1.0 wt%.
Catalyst characterization: XRD measurements were performed with a
a
Bruker Endeavour D4 with Cu K radiation (40 kV and 30 mA). Magic-
2
7
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referenced to a saturated Al(NO solution. In a typical experiment,
A
H
U
G
R
N
U
G
3 3
)
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(
(
(
0.5 mol%), n-dodecane (0.1 mmol, internal standard), and toluene
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Chem. Eur. J. 2012, 00, 0 – 0
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Published online: && &&, 2012
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8
&
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Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Synthesis of Methyl Esters and Imines
FULL PAPER
Heterogeneous Catalysis
P. Liu, C. Li,
E. J. M. Hensen* ............. &&&& — &&&&
Efficient Tandem Synthesis of Methyl
Esters and Imines by Using Versatile
Hydrotalcite-Supported Gold Nano-
particles
Golden Support! The Mg/Al atomic
ratio of hydrotalcite strongly affects
the catalytic performance of supported
gold nanoparticles for aerobic alcohol
oxidation, one-pot oxidative esterifica-
tion of alcohols to methyl esters, and
tandem oxidative coupling of alcohols
and amines to imines (see figure). The
tunability of the base properties makes
hydrotalcites ideal supports for optimal
gold catalysts for green tandem synthe-
sis under mild and base-additive-free
conditions.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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9
&
ÞÞ
These are not the final page numbers!