Efficient synthesis of amides and esters from alcohols under aerobic ambient conditions catalyzed by a Au/mesoporous Al2O3 nanocatalyst

Article abstract of DOI:10.1002/cssc.201403469

An efficient heterogeneous Au/mesoporous alumina nanocatalyst has been successfully developed for the synthesis of amides and esters from simple building blocks of readily available alcohols and amines. The processes were simple and were performed at room temperature and atmospheric pressure of O₂ to form the desired products with up to 97% isolated yield. The ability of Au/mesoporous alumina to catalyze these reactions under ambient conditions further enhances the sustainability of these chemical processes. Furthermore, the nanocatalyst was stable to air and water and could be recovered and reused easily. The enhanced catalytic activity of Au/mesoporous alumina might be attributed to the presence of negatively charged Au nanoparticles that could promote oxidation processes as well as the stability of the mesoporous alumina support calcined at a high temperature of 800°C. Gold for green: Gold nanoparticles supported on mesoporous alumina catalyze the efficient synthesis of amides and esters from simple building blocks of readily available alcohols and amines under ambient aerobic reaction conditions (R¹=aryl, alkyl, and R²=H, alkyl).

Full text of DOI:10.1002/cssc.201403469

DOI: 10.1002/cssc.201403469
Full Papers
Efficient Synthesis of Amides and Esters from Alcohols
under Aerobic Ambient Conditions Catalyzed by a Au/
Mesoporous Al O Nanocatalyst
2
3
[
a]
Leng Leng Chng, Jinhua Yang, and Jackie Y. Ying*
An efficient heterogeneous Au/mesoporous alumina nanocata-
lyst has been successfully developed for the synthesis of
amides and esters from simple building blocks of readily avail-
able alcohols and amines. The processes were simple and were
performed at room temperature and atmospheric pressure of
bility of these chemical processes. Furthermore, the nanocata-
lyst was stable to air and water and could be recovered and
reused easily. The enhanced catalytic activity of Au/mesopo-
rous alumina might be attributed to the presence of negatively
charged Au nanoparticles that could promote oxidation pro-
cesses as well as the stability of the mesoporous alumina sup-
port calcined at a high temperature of 8008C.
O to form the desired products with up to 97% isolated yield.
2
The ability of Au/mesoporous alumina to catalyze these reac-
tions under ambient conditions further enhances the sustaina-
Introduction
Amides and esters are important functional groups found ex-
tensively in fine chemicals, pharmaceuticals, natural products,
catalysts, which offer several advantages, such as high reactivi-
[9]
ty, ease of handling, air- and water-stability, and reusability.
[
1]
and materials. For example, the amide bond is crucial in the
formation of proteins as well as critical drugs such as antibiot-
ics (e.g., penicillin), antiviral drugs (e.g., Tamiflu), statins (e.g.,
Lipitor), and anesthetics (e.g., bupivacaine). Ester bonds are
found widely in the production of biodegradable polymers
For the oxidative amidation of alcohols with amines, Au-
based nanomaterials have been developed to produce the de-
[5]
sired amides in good to excellent yields. However, these re-
ported systems still present certain drawbacks, such as the use
[5e]
of a high Au loading (3.8 mol% Au), the application of heat
[5]
(e.g., polylactic acid), thermoplastics (e.g., polyethylene tereph-
(40–658C) for reaction completion, the use of organic sol-
[
5a–c]
thalate), and analgesics (e.g., aspirin). Amides and esters are
usually produced by the reaction of carboxylic acids (after con-
version to activated derivatives, such as acid chlorides or anhy-
vents,
and additional heat activation (1708C for 4–5 h) for
[5b,c]
the reuse of the recycled catalyst.
To improve the sustaina-
bility of this chemical process, the catalytic reaction should be
performed under ambient conditions using a low catalyst load-
ing. The recovery and reuse of the catalyst should also be ach-
ieved without an additional heat activation procedure.
[
2]
drides) with amines and alcohols, respectively. These tradi-
tional synthetic methods involve the use of stoichiometric
quantities of toxic and reactive coupling reagents, which thus
results in a high cost and excessive chemical waste generation.
The development of more sustainable and environmentally
For the reported Au-based catalytic systems involved in the
oxidative esterification of alcohols, some shortcomings include
[
3–5]
[6–8]
friendly methodologies for amide
and ester
bond forma-
the use of high temperatures (70–1308C) and O pressures (3–
2
[
8b–d]
tion has been reported by different research groups in recent
10 bar)
and a long reaction time (24 h) for a room-temper-
[4a]
[8a]
years. These include the direct amidation of aldehydes, hy-
ature, atmospheric O pressure system.
2
[
4f]
dration of nitriles, and oxidative coupling of alcohols and
We are interested in the engineering of nanocatalysts that
can perform multiple catalytic reactions with high atom effi-
ciencies, yields, and selectivities within a one-pot system,
which could lead to green and sustainable chemical process-
[
5]
amines for amide bond formation, and the esterification of al-
[
6]
[6a,7,8]
dehydes and oxidative esterification of alcohols
for ester
bond formation. Of these reported methods, the oxidative cou-
pling of alcohols and amines to produce amides and the oxi-
dative esterification of alcohols to produce esters are of partic-
ular interest as these systems use readily available alcohols
and amines as the starting materials, oxygen as the inexpen-
sive and environmentally friendly oxidant, and heterogeneous
[10]
es. Herein we report the development of Au nanoparticles
supported on mesoporous alumina for the efficient synthesis
of amides and esters from simple building blocks of alcohols
and amines under aerobic ambient conditions using a low Au
catalyst loading.
[a] Dr. L. L. Chng, Dr. J. Yang, Prof. J. Y. Ying
Institute of Bioengineering and Nanotechnology
Results and Discussion
3
1 Biopolis Way, The Nanos, Singapore 138669 (Singapore)
[11]
The support material, mesoporous alumina, was synthesized
by evaporation-induced self-assembly between the inorganic
aluminum isopropoxide precursor and the organic surfactant,
E-mail: jyying@ibn.a-star.edu.sg
Supporting Information for this article is available on the WWW under
http://dx.doi.org/10.1002/cssc.201403469.
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Pluronic P123, as a soft template, with 1,3,5-triisopropylben-
zene (TIPB) as the swelling agent. After the vigorous mixing of
the reaction mixture in ethanol under acidic conditions at
room temperature (RT) for 12 h, the mixture was kept under
static conditions at 45 and 608C for one and two days, respec-
tively. The resulting white solid was calcined in air for 4 h to
yield the desired product. Six different samples of mesoporous
alumina (Table 1) were prepared by varying the weight ratio of
TIPB/P123 (1, 2, and 3) and the calcination temperature (500,
sponding increase in the BET surface area of the mesoporous
2
À1
alumina samples (Al O -3-800: 114 m g , Al O -2-800:
2
3
2
3
2
À1
2
À1
165 m g , and Al O -1-800: 187 m g ). Conversely, the aver-
2
3
age pore width decreased from 21.7 to 19.8 and 14.5 nm with
a decrease in the weight ratio of TIPB/P123 from 3 to 2 and
1 after calcination at 8008C. At a fixed TIPB/P123 weight ratio
of 3, there was a slight increase in the average pore width
(from 16.9 to 21.7 nm) if the calcination temperature was in-
creased from 500 to 8008C. Correspondingly, as the calcination
temperature increased from 500 to 600, 700, and 8008C, the
BET surface area changed from
600, 700, and 8008C).
2
À1
1
63 to 172, 48, and 114 m g .
Table 1. Characteristics of mesoporous Al
2
O
3
materials as analyzed by N
Average
2
adsorption–desorption isotherms.
Al O -3-700 has the lowest BET
2
3
surface area, possibly because of
the incomplete pyrolysis of or-
ganics that results in the forma-
tion of a coating on the alumina,
as seen from the inhomogene-
ous grayish-black solid obtained
after calcination at 7008C (Fig-
ure S3).
Sample
Weight ratio
TIPB/P123
Calcination
temperature [8C]
Cumulative pore
BETsurface
area [m g
3
À1
2
À1
pore width [nm]
volume [cm g
]
]
2
Al O
2
Al O
2
Al O
2
Al O
2
Al O
2
Al O
3
3
3
3
3
3
-3-500
-3-600
-3-700
-3-800
-2-800
-1-800
3
3
3
3
2
1
500
600
700
800
800
800
16.9
17.6
18.5
21.7
19.8
14.5
0.64
0.72
0.24
0.61
0.83
0.74
163
172
48
114
165
187
Large mesopores were observed in the TEM images of the
mesoporous alumina samples synthesized with a TIPB/P123
weight ratio of 3 (Figure 1a–d), independent of the calcination
temperature. At the same calcination temperature of 8008C, if
the weight ratio of TIPB/P123 was decreased from 3 to 2 or 1,
the large porous structure was no longer observed in the TEM
images (cf. Figure 1d with Figure 1e–f). The TEM energy dis-
persive X-ray (EDX) spectra of the six mesoporous alumina
samples (Figure S1a–f) showed strong signals for Al and O,
which verifies the elemental composition of the alumina sam-
ples.
No XRD peaks were observed in the XRD patterns of the
mesoporous alumina calcined at 500 and 6008C (Al O -3-500
2
3
and Al O -3-600, respectively; Figure 2a and b), which confirms
2
3
their amorphous structure. Three very weak diffraction peaks
indexed to the 311, 400, and 440 reflections of g-Al O ,
(
2
3
JCPDS 10-0425) were seen in the XRD pattern of the sample
calcined at 7008C (Al O -3-700; Figure 2c). With an increase of
2
3
the calcination temperature to 8008C, crystalline peaks (in-
dexed to the 311, 222, 400, 511, 440, and 444 reflections of
g-Al O , JCPDS 10-0425) were clearly observed in the XRD pat-
2
3
terns of Al O -3-800, Al O -2-800, and Al O -1-800 (Figure 2d–f).
2
3
2
3
2
3
The low-angle XRD patterns of the six mesoporous alumina
samples displayed a single broad peak at 2q<28 (Figure S2),
which suggests the presence of a mesostructure that was dis-
[
12]
ordered.
The N2 adsorption–desorption isotherms of Al O -3-500,
2
3
Al O -3-600, Al O -3-800, Al O -2-800, and Al O -1-800 dis-
2
3
2
3
2
3
2
3
played typical type IV curves with H1 hysteresis (Figure 3a, b,
[
13]
d–f). For the sample calcined at 7008C (Al O -3-700), the N
2
2
3
adsorption–desorption isotherm exhibited an H3 hysteresis
loop (Figure 3c). The adsorption parameters of the mesopo-
rous alumina samples shown in Figure 3 are summarized in
Table 1. At a fixed calcination temperature of 8008C, if the
weight ratio of TIPB/P123 was decreased, there was a corre-
Figure 1. TEM images of mesoporous alumina with different TIPB/P123
weight ratios and calcination temperatures: a) Al -3-500, b) Al -3-600,
c) Al -3-700, d) Al -3-800, e) Al -2-800, and f) Al -1-800. Scale
bar=40 nm.
2
O
3
2 3
O
2
O
3
2
O
3
2
O
3
2 3
O
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termined by inductively coupled plasma mass spectrometry
(
ICP-MS) and ranged from 0.7 wt% to 1.0 wt%. The presence
of Au in these nanocatalysts was further confirmed by TEM-
EDX analysis (Figure S5). Depending on the mesoporous alumi-
na support used, the Au nanoparticles were 2–11 nm in diame-
ter (Figure 4), and the average particle sizes of Au were 5.5–
6.1 nm (Figure S6).
Figure 2. XRD patterns of various mesoporous alumina samples: a) Al
00, b) Al -3-600, c) Al -3-700, d) Al -3-800, e) Al -2-800, and
f) Al -1-800.
2 3
O -3-
5
2
O
3
2
O
3
2
O
3
2 3
O
2
O
3
Figure 3. N
na samples: a) Al
2 3
e) Al -2-800, and f) Al O
2
adsorption–desorption isotherms of various mesoporous alumi-
-3-500, b) Al -3-600, c) Al -3-700, d) Al -3-800,
-1-800.
2
O
3
2
O
3
2
O
3
2 3
O
2
O
3
Figure 4. TEM images of a) Au/Al
00, d) Au/Al -3-800, e) Au/Al
lysts. Scale bar=a–c, e–f) 40 and d) 20 nm.
2
O
3
-3-500, b) Au/Al
2
O
3
-3-600, c) Au/Al
2 3
O -3-
7
2
O
3
2
O
3
-2-800, and f) Au/Al
2
O
3
-1-800 nanocata-
Thermogravimetric analysis (TGA) and derivative thermo-
gram (DTG) curves of the as-synthesized alumina sample pre-
pared with a TIPB/P123 weight ratio of 3 exhibited four weight
loss steps (Figure S4). A small weight loss of 4.5 wt% between
The XRD patterns of the six Au/mesoporous Al O nanocata-
2
3
50 and 1008C could be ascribed to the desorption of adsorbed
lysts are shown in Figure 5. For Au/Al O -3-500, Au/Al O -3-600,
2 3 2 3
water and volatile organic molecules. The decomposition of
and Au/Al O -3-700 (Figure 5a–c), the alumina support was
2 3
Pluronic P123 and other organic compounds at ~170 and
amorphous, but crystalline peaks were observed for Au at
2q=38.18 (indexed to the 111 reflection of Au (JCPDS 4-
0784)). The XRD patterns of Au/Al O -3-800, Au/Al O -2-800,
~
3008C led to substantial weight losses of 8.3 and 30.3 wt%,
respectively. The 17.2 wt% loss at ~4708C could be caused by
2
3
2
3
dehydroxylation upon the conversion of aluminum oxide hy-
and Au/Al O -1-800 nanocatalysts consisted of peaks associat-
2 3
[
14]
droxide into alumina.
ed with g-Al O nanocrystals and Au nanocrystals (Figure 5d–f).
2 3
The six mesoporous alumina samples were employed as
supports for Au catalysts. Au/mesoporous Al O nanocatalysts
X-ray photoelectron spectroscopy (XPS) was used to deter-
mine the surface chemistry of the Au nanocrystals in the six
2
3
were prepared by the reduction of HAuCl in water with NaBH4
Au/mesoporous Al O3 nanocatalysts. The Au4f XPS spectra
4
2
in the presence of l-lysine and mesoporous alumina. The Au
(Figure 6) for all the nanocatalysts could be curve-fitted to one
set of doublets. The Au4f7/2 peak of the six Au/mesoporous
loadings on the Au/mesoporous Al O nanocatalysts were de-
2
3
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Table 2. Amidation of benzyl alcohol with aniline over Au/mesoporous
[a]
alumina nanocatalysts.
[c]
Entry
Catalyst
Au
mol%]
Au loading
[wt%]
Yield
[%]
[b]
[
1
2
3
4
5
6
7
8
9
Au/Al
Au/Al
Au/Al
Au/Al
Au/Al
Au/Al
Au/Al
Au/Al
Au/Al
Au/Al
Au/Al
Au/Al
2
2
2
2
2
2
2
2
2
2
2
2
O
O
O
O
O
O
O
O
O
O
O
O
3
3
3
3
3
3
3
3
3
3
3
3
-3-500
-3-500
-3-600
-3-600
-3-700
-3-700
-3-800
-3-800
-2-800
-2-800
-1-800
-1-800
0.5
1.0
0.5
1.0
0.5
1.0
0.5
1.0
0.5
1.0
0.5
1.0
–
–
–
–
–
–
1.0
–
0.7
0.7
0.7
0.7
0.9
0.9
1.0
1.0
0.8
0.8
0.9
0.9
–
–
–
–
–
–
–
–
85
88
83
84
76
76
96
98
95
97
94
96
0
0
0
0
0
0
0
0
10
1
1
Figure 5. XRD patterns of a) Au/Al
-700, d) Au/Al -3-800, e) Au/Al
lysts.
2
O
3
-3-500, b) Au/Al
-2-800, and f) Au/Al O
2
O
3
-3-600, c) Au/Al
2 3
O -
12
13
14
15
16
17
18
19
20
3
2
O
3
2
O
3
2 3
-1-800 nanocata-
Al
Al
Al
Al
Al
Al
2
2
2
2
2
2
O
O
O
O
O
O
3
-3-500
3
-3-600
3
-3-700
3
-3-800
3
-2-800
3
-1-800
HAuCl
no catalyst
4
·3H
2
O
[
a] Reaction conditions: Au catalyst (0.5 or 1 mol%), aniline (0.05 mmol),
benzyl alcohol (0.1 mmol), LiOH (0.1 mmol), and H O (0.2 mL, purged
with O for 5 min), RT, 14 h, under O . [b] Determined by ICP-MS analysis.
c] GC–MS yield based on aniline using n-dodecane as an internal stan-
dard.
2
2
2
[
The six Au/mesoporous alumina nanocatalysts were investi-
gated for their activities in the direct oxidative amidation of al-
cohols with amines using the model substrates benzyl alcohol
and aniline under ambient conditions (Table 2). The initial
screening experiments showed that with a catalyst loading of
0
.5 mol% Au, LiOH as the base, water as the solvent, and a re-
Figure 6. XPS patterns of a) Au/Al
00, d) Au/Al -3-800, e) Au/Al
2
O
3
-3-500, b) Au/Al
2
O
3
-3-600, c) Au/Al
-1-800.
2 3
O -3-
action time of 14 h at RT under an O atmosphere, three of the
7
2
O
3
2
O
3
-2-800, and f) Au/Al
2
O
3
2
six nanocatalysts, that is, Au/Al O -3-800, Au/Al O -2-800, and
2
3
2
3
Au/Al O -1-800, provided excellent yields of 94–96% (Table 2,
2
3
entries 7, 9, and 11). An increase of the catalyst loading to
1.0 mol% Au resulted in a slightly improved yield of the de-
sired product (96–98%; Table 2, entries 8, 10, and 12). The ami-
dation reaction did not proceed in the absence of the Au/mes-
oporous alumina nanocatalyst (Table 2, entry 20) or in the pres-
ence of the mesoporous alumina support alone (Table 2, en-
alumina nanocatalysts (binding energy (BE)=83.5–83.7 eV) was
0
lower than the BE=84.0 eV value for bulk metallic gold (Au ).
A negative shift to lower BE could be because of the nanocrys-
tal size effect (which results from an increase in the number of
low-coordinated Au surface atoms) or an electron transfer
[15–16]
from the metal oxide support to the Au nanoparticles.
Lower Au4f7/2 BEs than that of bulk Au have been reported for
tries 13–18). If the homogeneous Au salt (HAuCl ) was used as
4
a catalyst (Table 2, entry 19), no amide was detected in the
GC–MS analysis of the reaction mixture.
[
15b]
Au nanocrystals on g-Al O (BE=83.7 eV),
Au nanocrystals
2
3
[
16a]
on MoO (BE=82.9 eV),
Au clusters stabilized by poly(N-
The reactivity of the six Au/mesoporous alumina nanocata-
lysts could be correlated to the stability of these materials in
the solvent (water). The physical state of the three most active
nanocatalysts, Au/Al O -3-800, Au/Al O -2-800, and Au/Al O -1-
x
[
16b]
vinyl-2-pyrrolidinone) (BE=82.7 eV), and poly(N-vinyl-2-pyr-
rolidinone)-capped micrometer-sized Au plates (BE=
[
15d]
83.6 eV).
The lower Au4f7/2 BEs in these reports were attrib-
2
3
2
3
2
3
uted to the negative charge states of Au. Hence, for our Au/
mesoporous alumina nanocatalysts, the negative shift of the
Au4f7/2 peak likely arose from an electron transfer from the
alumina support to the Au nanocrystals.
800, remained unchanged if the materials were left suspended
in water for 24 h (Figure S7). These three nanocatalysts were
prepared with supports that crystallized as g-Al O after calci-
2
3
nation at 8008C. In contrast, the less active nanocatalysts, Au/
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Al O -3-500, Au/Al O -3-600, and Au/Al O -3-700 (prepared
2
3
2
3
2
3
Table 3. Recycling of Au/Al
in the amidation of benzyl alcohol with aniline.
2
O
3
-3-800, Au/Al
2
O
3
-2-800, and Au/Al
2
O
3
-1-800
with amorphous alumina supports calcined at 500, 600, and
008C), started to aggregate if they were left in contact with
[a]
7
[b]
Nanocatalyst
Yield of product on successive runs [%]
water for one day (Figure S7). Similar results were attained if
the six Au/mesoporous alumina nanocatalysts were suspended
in 0.5m LiOH aqueous solution for 14 h (Figure S8). This aggre-
gation could reflect a less stable dispersion of the nanocata-
lysts in water, which led to lower catalytic activities.
1
2
3
4
5
6
Au/Al
Au/Al
Au/Al
2
2
2
O
3
O
3
O
3
-3-800
-2-800
-1-800
98
97
96
96
95
93
93
92
89
92
91
87
92
85
87
91
85
86
[
a] Reaction conditions: Au catalyst (1 mol%), aniline (0.05 mmol), benzyl
alcohol (0.1 mmol), LiOH (0.1 mmol), and H O (0.2 mL, purged with O for
min), RT, 14 h, under O . [b] GC–MS yield based on aniline using n-do-
The stability of the six mesoporous alumina supports in
aqueous LiOH solution was also investigated by stirring the
support materials in 0.5m LiOH. Very small quantities of Al (1–
2
2
5
2
decane as an internal standard.
3
%) were leached into the aqueous solution after 14 h at RT
(Table S1). Similarly, minor amounts of Al (2–4%) were detected
in the aqueous reaction media after the amidation reaction
with the six Au/mesoporous alumina nanocatalysts (Table S2).
The recyclability of the three most active nanocatalysts, Au/
Al O -3-800, Au/Al O -2-800, and Au/Al O -1-800, was investi-
product were attained if the reaction was performed in the
presence of air or Ar (83 and 11 %, respectively; Table 4, en-
tries 17–18) instead of O . A decrease of the Au catalyst load-
2
3
2
3
2
3
2
gated by the recovery of the materials by centrifugation after
the addition of ethyl acetate followed by washing with ethyl
acetate three times. The nanocatalysts recovered by centrifuga-
tion were dried by using a rotary evaporator before use in
a subsequent run. Although there was a gradual decrease in
the activities of the three nanocatalysts upon recycling, 85–
ing to 0.2 mol% led to a significant decrease in the product
yield (69%; Table 4, entry 21), which did not improve substan-
tially if the reaction temperature was increased to 408C (72%;
Table 4, entry 22). After detailed investigation, we found the
best reaction conditions to be 1 mol% Au, 2 equivalents of
LiOH, 2 equivalents of benzyl alcohol, water as the solvent, and
91% yield was still achieved in the sixth run (Table 3). There
a reaction time of 14 h at RT under an O atmosphere (Table 4,
2
was no change in the size of the Au nanocrystals after six runs
of the amidation reaction, as
entry 23), which led to 98% yield.
confirmed by TEM (Figure S9a).
There was also no significant
[a]
2 3
Table 4. Optimization of the amidation of benzyl alcohol with aniline over Au/Al O -3-800.
change in the position of the
Au4f XPS peaks after the reac-
tion (Figure S10b). Hence, the
gradual decrease in the product
yield might be attributed to
some loss of the nanocatalysts
in the recovery process.
[b]
Entry
Au
[mol%]
T
[8C]
t
[h]
Solvent
Base
Benzyl alcohol
[equiv.]
Atmosphere
Yield
[%]
1
2
3
4
5
6
7
8
9
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.2
0.2
1
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
408C
RT
408C
RT
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
24
14
14
14
14
H
2
O
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
NaOH (2 equiv.)
KOH (2 equiv.)
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1.5
2
2
2
2
2
2
2
O
2
94
0
0
0
0
12
87
0
12
0
78
42
0
Optimization of the reaction
conditions for the direct amida-
tion reaction was performed
using the most active nanocata-
lyst, Au/Al O -3-800. Different re-
THF
DMF
O2
O
O
O
O
2
2
2
2
CH
DMSO
CH Cl
3
CN
2
2
2
3
hexanes
MeOH
toluene
O2
action conditions such as sol-
vent, base, reaction temperature,
and amount of reactants used
O
O
O
O
2
2
2
2
1
0
CHCl
3
1
1
H
2
O
were
Among the 10 solvents tested
Table 4, entries 1–10), water was
investigated
(Table 4).
12
13
2
H O
O2
H
H
H
H
2
O
2
O
2
O
2
O
K
2
CO
3
(2 equiv.)
(2 equiv.)
O
O
O
O
2
2
2
2
1
1
1
17
18
4
5
6
Cs
2
CO
3
1
(
LiOH (1.1 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
LiOH (2 equiv.)
85
91
83
11
96
96
69
72
98
found to be the best solvent for
this reaction (94%, Table 4,
entry 1). The use of the stronger
base NaOH or KOH resulted in
lower yields of the product (42–
[
c]
2
H O
Air
Ar
[
d]
H
H
H
H
2
O
2
O
2
O
2
O
19
20
21
O
O
O
2
2
2
7
8%; Table 4, entries 11–12), and
22
23
2
H O
O2
very little or no product was ob-
tained if weak bases such as
H
2
O
O
2
[a] Reaction conditions: Au/Al
2 3 2
O -3-800 catalyst, aniline (0.05 mmol), benzyl alcohol, LiOH, and H O (0.2 mL,
K2CO3 and Cs CO3 were em-
purged with O for 5 min). [b] GC–MS yield based on aniline using n-dodecane as an internal standard. [c] Sol-
2
2
vent was purged with air for 5 min. [d] Three freeze–pump–thaw cycles were performed on the reaction mix-
ture before the introduction of Ar gas into the glass vial.
ployed (0–1%; Table 4, en-
tries 13–14). Lower yields of the
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tion gave good yields of the de-
sired amides (85–89%; Table 5,
[a,b]
2 3
Table 5. Scope of the direct amidation of alcohols with amines catalyzed by Au/Al O -3-800.
3
j, 3n, 3r). Electron-withdrawing
halogen groups (ÀF, ÀCl, ÀBr) at
either the meta or para position
of the aniline moiety also fur-
nished good to excellent yields
of the product (72–94%; Table 5,
3k–m, 3o–q). However, low
yields of 30–47% were attained
if the halogen groups (ÀF, ÀCl,
ÀBr) were at the ortho position
of the aniline moiety (Table 5,
Entry Product
Entry Product
Entry Product
Entry Product
1
2
3
4
5
9
6
7
8
3
s–u). For dialkyl secondary
amine substrates, such as di-
methyl and cyclic secondary
amines (four-, five-, or six-mem-
bered rings), good yields of the
required amides were achieved
10
14
18
11
15
19
12
16
20
(
80–91%; Table 5, 3v–z).
1
1
3
7
To investigate the amidation
reaction mechanism, we per-
formed a number of control ex-
periments. No amide product
was obtained if benzoic acid was
reacted with aniline under the
optimized reaction conditions
2
2
1
5
22
26
23
24
(
Scheme S1). This result indicat-
ed that benzoic acid was not an
intermediate for this reaction.
The reaction of benzaldehyde
with aniline gave 50% of the
amide product and 43% of the
[
(
a] Reaction conditions: Au/Al
2
O
3
-3-800 catalyst (1 mol%), 1 (0.4 mmol), 2 (0.2 mmol), LiOH (0.4 mmol), and H
2
O
imine
byproduct
(Table S3,
0.8 mL, purged with O for 5 min), RT, 14 h, under O
2
2
. [b] Isolated yields. [c] 0.5 mol% Au catalyst. [d] Dimethyl-
entry 1). The amide yield could
be improved to 90% if the ben-
zaldehyde substrate was added
in small portions at regular inter-
vals of 30 min over a period of
amine hydrochloride and 0.6 mmol of LiOH were used. [e] Azetidine hydrochloride and 0.6 mmol of LiOH were
used.
After the optimized conditions for this amidation reaction
were established, we investigated the scope of the direct ami-
dation reaction with Au/Al O -3-800 using a variety of substi-
10 h (Table S3, entry 3). This finding suggested that benzalde-
hyde was an intermediate, and a low concentration was re-
quired to achieve high selectivity. The reaction of the imine
compound over Au/Al O -3-800 under the optimized reaction
2
3
tuted benzyl alcohols and aryl and alkyl amines (Table 5). For
the substituted benzyl alcohol substrates, electron-withdraw-
2
3
conditions yielded no amide product (Scheme S2). This result
suggested that the imine byproduct could not be hydrated
back to the hemiaminal intermediate, and its formation led to
a decrease in the amide product yield.
ing (ÀF, ÀCl, ÀBr) and weakly electron-donating (ÀCH ) func-
3
tional groups at the para position gave good yields of the de-
sired products (75–95%; Table 5, 3b, 3d–f). However, the pres-
ence of a stronger electron-donating group such as ÀOCH at
Based on the above findings, a tentative mechanism for the
direct amidation reaction from benzyl alcohol and amine cata-
lyzed by Au/mesoporous alumina is proposed (Scheme 1). Au/
Al O -3-800 catalyzed the oxidation of aryl alcohol I to alde-
3
the para position resulted in a lower yield of the expected
product (56%; Table 5, 3c). Electron-withdrawing halogen
groups (ÀF, ÀCl, ÀBr) at the meta position of the benzyl alcohol
moiety also gave excellent yields of the amides (90–94%;
Table 5, 3g–i).
2
3
hyde II. Amine III reacted with II to produce the hemiaminal
intermediate IV. The hemiaminal intermediate IV can either be
oxidized to the product VI or dehydrated to form the imine
byproduct V. Under the current oxidative reaction conditions,
Au/Al O -3-800 was able promote the oxidation of IV to form
Different types of substituted aromatic primary amines and
dialkyl secondary amine substrates were studied with Au/
Al O -3-800 (Table 5, 3j–z). Aromatic amines with the weakly
2
3
2
3
electron-donating ÀCH group at the ortho, meta, or para posi-
the amide product VI, and thus compete successfully against
3
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Full Papers
gated (Table 8, entries 1–15), and
a MeOH/hexanes solvent mixture
of 1:4 furnished the highest
yield (94%; Table 8, entry 13).
Much lower product yields were
achieved if stronger hydroxide
bases, LiOH, NaOH, and KOH,
were used (0–22%; Table 8, en-
tries 16–18). Na CO gave a low
2
3
product yield (31%; Table 8,
entry 19), whereas Cs CO and
2
3
Scheme 1. Proposed mechanism of amidation of benzyl alcohol over Au/mesoporous alumina nanocatalyst.
R =aryl, alkyl; R =H, alkyl.
K PO provided good yields (85–
3 4
1
2
90%; Table 8, entries 20–21). O2
the dehydration reaction that led to the formation of the un-
wanted byproduct V. The reactivity of the Au/Al O -3-800
Table 6. Oxidative esterification of benzyl alcohol with methanol over
Au/mesoporous alumina nanocatalysts.
2
3
[a]
nanocatalyst to promote the oxidation of IV to VI might arise
from the presence of negatively charged Au nanocrystals as
observed by XPS analysis (vide supra). Negatively charged Au
nanoparticles have been reported to be highly active catalysts
[
16]
for the selective aerobic oxidation of alcohols. In our case,
the negatively charged Au nanocrystals could promote not
only the selective aerobic oxidation of aryl alcohol I to alde-
hyde II but also the oxidation of the hemiaminal intermediate
IV to the amide product VI.
[
b]
[c]
Entry
Catalyst
Au
mol%]
Au loading
[wt%]
Yield
[%]
[
1
2
3
4
5
6
7
8
9
Au/Al
Au/Al
Au/Al
2
2
2
O
O
O
3
3
3
-3-500
-3-500
-3-600
0.5
1.0
0.5
1.0
0.5
1.0
0.5
1.0
0.5
1.0
0.5
1.0
–
–
–
–
–
–
–
0.7
0.7
0.7
0.7
0.9
0.9
1.0
1.0
0.8
0.8
0.9
0.9
–
–
–
–
–
–
–
80
87
82
88
86
93
94
99
96
99
95
99
0
0
0
0
0
0
0
In addition to the direct amidation reaction, the six Au/Al O3
Au/Al O -3-600
2
2
2
2
2
2
3
3
3
3
3
Au/Al
Au/Al
Au/Al
Au/Al
O
O
O
O
-3-700
-3-700
-3-800
-3-800
nanomaterials were also examined for the oxidative esterifica-
tion of alcohols using the model substrates benzyl alcohol and
methanol under ambient conditions (Table 6). The initial
screening results showed that with a catalyst loading of
Au/Al O -2-800
2
2
2
2
3
3
3
3
10
Au/Al
Au/Al
Au/Al
O
O
O
-2-800
-1-800
-1-800
0
.5 mol% Au, K CO as the base, MeOH/hexanes (1:4) as the
2 3
1
1
solvent, and 14 h at RT under an O atmosphere, Au/Al O -3-
2
2
3
12
8
00, Au/Al O -2-800, and Au/Al O -1-800 displayed the highest
2 3 2 3
13
14
2 3
Al O -3-500
activities (94–96% yields; Table 6, entries 7, 9, and 11). If the
catalyst loading was increased to 1.0 mol% Au, the yields im-
proved to 99% (Table 6, entries 8, 10, and 12). No product was
obtained if the esterification reaction was performed in the ab-
sence of Au/mesoporous alumina nanocatalysts (Table 6,
entry 19) or in the presence of the mesoporous alumina sup-
port alone (Table 6, entries 13–18).
Al O -3-600
2
2
2
2
2
3
3
3
3
3
1
1
1
1
5
6
7
8
Al
Al
Al
Al
O
O
O
O
-3-700
-3-800
-2-800
-1-800
19
No catalyst
[
a] Reaction conditions: Au catalyst (0.5 or 1 mol%), benzyl alcohol
(0.05 mmol), K CO (0.05 mmol), and MeOH/hexanes (1:4, 0.2 mL, purged
2
3
The recyclability of the three most active nanocatalysts, Au/
Al O -3-800, Au/Al O -2-800, and Au/Al O -1-800, was examined
2 2
with O for 5 min), RT, 14 h, under O . [b] Determined from ICP-MS analy-
sis. [c] GC–MS yield based on benzyl alcohol using n-dodecane as an in-
ternal standard.
2
3
2
3
2
3
by recovering the nanocatalysts by centrifugation after the ad-
dition of ethyl acetate, followed by three more ethyl acetate
washes. The nanocatalysts were recovered by centrifugation
and dried by using a rotary evaporator before use in the next
run. All three Au/mesoporous alumina nanocatalysts displayed
good recyclability and achieved 91–97% yields even after six
runs (Table 7). The size of the Au nanocrystals remained un-
changed after the sixth run, as confirmed by the TEM image
Table 7. Recycling of Au/Al
in the oxidative esterification of benzyl alcohol with methanol.
2
O
3
-3-800, Au/Al
2
O
3
-2-800, and Au/Al
2
O
3
-1-800
[a]
[b]
Nanocatalyst
Yield of product on successive runs [%]
1
2
3
4
5
6
(
Figure S9b). No significant change in the position of the Au4f
Au/Al
Au/Al O -2-800
Au/Al
2
O
3
-3-800
99
99
99
99
99
99
99
99
99
98
98
98
97
98
97
97
95
91
XPS peaks was observed after six runs of the reaction (Fig-
ure S10c).
2
2
3
3
O
-1-800
The reaction conditions for the direct oxidative esterification
reaction were examined systematically using Au/Al O -3-800,
[
K
5
a] Reaction conditions: Au catalyst (1 mol%), benzyl alcohol (0.05 mmol),
CO
3
(0.05 mmol), and MeOH/hexanes (1:4, 0.2 mL, purged with O
2
for
2
3
2
min), RT, 14 h, under O
2
. [b] GC–MS yield based on benzyl alcohol using
which showed excellent activity and the best recyclability
Table 8). Various solvents and solvent mixtures were investi-
n-dodecane as an internal standard.
(
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Full Papers
halogen groups (ÀF, ÀCl, ÀBr) at the meta position of
the benzyl alcohol moiety also furnished good yields
of the product (75–90%; Table 9, 4h–k). Allylic alco-
hol could be esterified in this reaction (70%; Table 9,
Table 8. Optimization of the oxidative esterification of benzyl alcohol with methanol
over Au/Al O -3-800.
2 3
[
a]
4
l), and diesters were obtained easily (72–85%;
Table 9, 4m–n).
[b]
Entry
Au
mol%]
Solvent
Base
Atmosphere Yield
[%]
Control experiments were conducted to study the
reaction mechanism for this esterification reaction.
Under the optimized reaction conditions, no ester
product was achieved if benzoic acid was reacted
with methanol (Scheme S3), which confirms that ben-
zoic acid was not an intermediate for this reaction.
The reaction of benzaldehyde with methanol fur-
nished 97% of the ester product (Scheme S4). This
finding suggested that benzaldehyde was an inter-
mediate in the esterification reaction. A tentative
mechanism for the oxidative esterification of benzyl
alcohol with methanol over Au/Al O -3-800 is pro-
[
1
2
3
4
5
6
7
8
9
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
MeOH
MeOH/hexanes (1:1)
MeOH/H O (1:1)
2
MeOH/THF (1:1)
MeOH/toluene (1:1)
MeOH/CHCl
MeOH/CH Cl
MeOH/DMF (1:1)
MeOH/DMSO (1:1)
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
(1 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
83
90
54
60
73
67
89
44
4
43
12
83
94
38
45
9
3
(1:1)
(1:1)
2
2
10
MeOH/CH
3
CN (1:1)
11
MeOH/EtOAc (1:1)
MeOH/hexanes (1:9)
MeOH/hexanes (1:4)
MeOH/CH
MeOH/CH
MeOH/hexanes (1:4)
MeOH/hexanes (1:4)
MeOH/hexanes (1:4)
MeOH/hexanes (1:4)
MeOH/hexanes (1:4)
MeOH/hexanes (1:4)
MeOH/hexanes (1:4)
MeOH/hexanes (1:4)
MeOH/hexanes (1:4)
MeOH/hexanes (1:4)
12
13
14
15
16
17
18
19
20
21
22
23
24
2
3
posed (Scheme 2). The oxidation of the aryl alcohol I
to the aldehyde II was catalyzed by the Au/mesopo-
rous alumina nanocatalyst. Aldehyde II then reacted
with methanol to form the hemiacetal intermediate
VII. The oxidation of VII catalyzed by Au/Al O -3-800
2
Cl
Cl
2
(1:9)
(1:4)
2
2
LiOH (1 equiv.)
NaOH (1 equiv.)
KOH (1 equiv.)
0
22
31
90
85
90
61
<1
99
2
3
Na
2
CO
CO
PO
CO
3
(1 equiv.)
would result in the formation of the ester product
Cs
2
3
(1 equiv.)
VIII.
K
3
K
2
K
2
K
2
4
(1 equiv.)
(0.5 equiv.)
(1 equiv.)
(1 equiv.)
(1 equiv.)
3
3
3
[
c]
CO
CO
air
Ar
[
d]
25
K
2
CO
3
O
2
Conclusions
[
a] Reaction conditions: Au/Al
2 3
O -3-800, benzyl alcohol (0.05 mmol), base, and solvent
An efficient heterogeneous Au/mesoporous alumina
nanocatalyst was developed successfully for the
direct amidation of benzyl alcohols with amines in
water and the oxidative esterification of alcohols
with methanol under aerobic conditions. The reac-
(
0.2 mL, purged with O for 5 min), RT, 14 h. [b] GC–MS yield based on benzyl alcohol
2
using n-dodecane as an internal standard. [c] Solvent was purged with air for 5 min.
d] Three freeze–pump–thaw cycles were performed on the reaction mixture before
[
the introduction of Ar gas into the glass vial.
gas was critical in this esterifica-
tion reaction as no product was
formed if the reaction was per-
formed under Ar (Table 8,
entry 24), and a lower yield of
Scheme 2. Proposed mechanism of oxidative esterification of benzyl alcohol catalyzed by Au/mesoporous alumi-
na.
61% was achieved if air was
used instead of O2 (Table 8,
entry 23). From these systematic
investigations, we found the optimized reaction conditions to
be 1 mol% Au, 1 equivalent of K CO , a MeOH/hexanes solvent
tions were performed easily under ambient conditions without
the need for heating or high O pressure. Moreover, the nano-
2
3
2
mixture (1:4), and a reaction time of 14 h at RT under an O at-
catalyst was stable to air and water and could be recovered
and reused easily.
2
mosphere (Table 8, entry 25).
Next, the scope of the oxidative esterification reaction for
a variety of substituted benzyl alcohols was examined with
Au/Al O -3-800 (Table 9). We found that electron-donating
Experimental Section
2
3
(
ÀCH , ÀOCH ) and halogen functional groups (ÀF, ÀCl, ÀBr) at
Materials
3
3
the para position provided good to excellent yields of the de-
sired esters (84–97%; Table 9, 4b–f). The presence of an elec-
Difunctional block copolymer surfactant based on ethylene oxide
and propylene oxide Pluronic P123 (M =5750 gmol ) was pur-
chased from BASF. All other reagents were purchased from Aldrich,
Fluka, and Merck, and used as received. Silica gel 60 (230–
400 mesh, Merck) was used for column chromatography.
À1
av
tron-withdrawing ÀNO group at the para position resulted in
2
a low yield of the expected product (50%; Table 9, 4g). The
electron-donating ÀCH substituent and electron-withdrawing
3
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Full Papers
Synthesis of mesoporous alu-
mina
Table 9. Scope of the oxidative esterification of substituted benzyl alcohols with methanol catalyzed by Au/
Al O -3-800.
2 3
[a,b]
Mesoporous alumina materials
were synthesized by the evapora-
tion-induced self-assembly method
[11b]
using an established procedure
Entry
1
Product
Entry
2
Product
Entry
3
Product
Entry
4
Product
with some modifications. Alumi-
num isopropoxide, Pluronic P123,
and TIPB were used as the precur-
sor, template, and swelling agent,
respectively. Three different TIPB/
P123 weight ratios (1, 2, and 3)
were used in the synthesis of mes-
oporous alumina. In general, TIPB
5
9
6
7
8
(
6.0 g) was added to a solution of
Pluronic P123 (2.0 g) in ethanol
40 mL) and stirred vigorously at
(
RT under air for 1 h. Aluminum iso-
propoxide (4.08 g), concentrated
HCl (3.2 mL), and citric acid (0.9 g)
were added, and the resulting mix-
ture was stirred vigorously at RT
under air for 12 h. The reaction
mixture was transferred to a Petri
dish and evaporated in an oven at
10
11
12
13
14
4
58C for 24 h and at 608C for 48 h.
[a] Reaction conditions: Au/Al
2
O
3
-3-800 (1 mol%), 1 (0.2 mmol), K
2
CO
3
(0.2 mmol) and MeOH/hexanes (1:4,
The white solid was calcined at
0
.8 mL, purged with O
2
for 5 min), RT, 14 h, under O
2
. [b] Isolated yield. [c] 0.5 mol% Au catalyst.
500, 600, 700, or 8008C under air
for 4 h with a heating rate of
À1
1
8Cmin . The mesoporous alumi-
na materials were labeled as Al O -
2
3
Characterization
a-b, in which a and b represent the TIPB/P123 weight ratio and the
calcination temperature, respectively. The six mesoporous alumina
materials (Al O -3-500, Al O -3-600, Al O -3-700, Al O -3-800, Al O -
2
TEM was performed by using a FEI Tecnai G F20 electron micro-
scope operated at 200 kV with the software package for automat-
ed electron tomography. For TEM studies, a drop of the nanomate-
rial solution was dispensed onto a 3 mm carbon-coated copper
grid. Excess solution was removed by an absorbent paper, and the
sample was dried under air in an oven at 808C. EDX analysis of the
2
3
2
3
2
3
2
3
2
3
2
-800, and Al O -1-800) were characterized by TEM, TEM-EDX, XRD,
2 3
and N adsorption–desorption isotherms.
2
Synthesis of Au/mesoporous alumina nanocatalysts
2
nanomaterials was performed by using the FEI Tecnai G F20 elec-
Mesoporous alumina (0.200 g) in water (4.4 mL) was sonicated for
tron microscope equipped with an EDX detector. XPS analysis was
conducted by using a VG ESCALAB MKII spectrometer. The powder
XRD patterns were collected by using PANalytical X’Pert PRO and
3
0 s to disperse the solids. HAuCl4 aqueous solution (0.0186 mL,
0.58m) was added with vigorous stirring, followed by the addition
of l-lysine (0.5 mL, 0.53m). The suspension was stirred vigorously
at RT under air for 30 min. NaBH aqueous solution (0.25 mL,
4
Bruker D8 ADVANCE X-ray diffractometers using CuK irradiation
a
1
13
(
l=1.5406 Š). H and C NMR spectra were collected in CDCl by
3
using a Bruker AV-400 spectrometer at 258C. Chemical shifts were
reported in ppm from tetramethylsilane with the solvent reso-
nance as the internal standard. GC–MS analysis was performed by
using a Shimadzu GCMS-QP2010 spectrometer. ICP-MS analyses
0.35m) was added dropwise, followed by HCl aqueous solution
(0.25 mL, 0.3m). The resulting reddish suspension was stirred at RT
under air for 18 h. The Au/mesoporous alumina was collected by
centrifugation (10000 rpm for 20 min), washed twice with deion-
ized water (10 mL) and once with acetone (10 mL), and dried at RT
under vacuum overnight. The material was characterized by TEM,
TEM-EDX, XRD, and ICP-MS.
were performed by using a PerkinElmer Elan DRC II. N adsorption–
2
desorption isotherms were measured at 77 K by using a Micromerit-
ics Tristar system, and the sample was degassed at 1808C for 12 h
before analysis. The surface area was calculated using the BET
method using adsorption data in a relative pressure range of 0.06–
0
.3. The pore size and total pore volume were derived from the ad-
Synthesis of amides
sorption isotherm using the Barrett–Joyner–Halenda (BJH) model.
TGA was conducted by using a PerkinElmer Pyris 1 thermogravimet-
ric analyzer, and the samples were heated at 108Cmin from 25–
The general procedure for the direct amidation of substituted
benzyl alcohol with amine was as follows. A mixture of the Au/
Al O -3-800 nanocatalyst (1 mol% Au), amine (0.2 mmol), substitut-
À1
2
3
9
008C in flowing air.
ed benzyl alcohol (0.4 mmol), lithium hydroxide (0.4 mmol), and
deionized water (0.8 mL, purged with O for 5 min) were added to
2
a 10 mL glass vial equipped with a rubber septum. The headspace
in the glass vial was purged with O , and the reaction mixture was
2
subjected to sonication to disperse the catalyst. The reaction mix-
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1924
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Papers
ture was stirred at RT under an O balloon for 14 h. EtOAc (3 mL)
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was added, and the biphasic mixture was stirred at RT for 30 min.
The mixture was centrifuged at 4500 rpm for 5 min. The upper or-
ganic layer that contained the product was recovered, and the
lower layer that contained the catalyst was extracted with EtOAc
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Received: December 28, 2014
Revised: March 11, 2015
Published online on April 29, 2015
ChemSusChem 2015, 8, 1916 – 1925
www.chemsuschem.org
1925
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim