Graphite-supported gold nanoparticles as efficient catalyst for aerobic oxidation of benzylic amines to imines and N-substituted 1,2,3,4- tetrahydroisoquinolines to amides: Synthetic applications and mechanistic study

Article abstract of DOI:10.1002/asia.200900261

Selective oxidation of amines using oxygen as terminal oxidant is an important area in green chemistry. In this work, we describe the use of graphite-supported gold nanoparticles (AuNPs/C) to catalyze aerobic oxidation of cyclic and acyclic benzylic amines to the corresponding imines with moderate-to-excellent substrate conversions (43-100%) and product yields (66-99%) (19 examples). Oxidation of N-substituted 1,2,3,4- tetrahydroisoquinolines in the presence of aqueous NaHCO₃ solution gave the corresponding amides in good yields (83-93%) with high selectivity (up to amide/enamide=93:4) (6 examples). The same protocol can be applied to the synthesis of benzimidazoles from the reaction of o-phenylenediamines with benzaldehydes under aerobic conditions (8 examples). By simple centrifugation, AuNPs/C can be recovered and reused for ten consecutive runs for the oxidation of dibenzylamine to N-benzylidene(phenyl) methanamine without significant loss of catalytic activity and selectivity. This protocol "AuNPs/C+O ₂" can be scaled to the gram scale, and 8.9 g (84% isolated yield) of 3,4-dihydroisoquinoline can be obtained from the oxidation of 10 g 1,2,3,4-tetrahydroisoquinoline in a onepot reaction. Based on the results of kinetic studies, radical traps experiment, and Hammett plot, a mechanism involving the hydrogen-transfer reaction from amine to metal and oxidation of M-H is proposed.

Full text of DOI:10.1002/asia.200900261

DOI: 10.1002/asia.200900261
Graphite-Supported Gold Nanoparticles as Efficient Catalyst for Aerobic
Oxidation of Benzylic Amines to Imines and N-Substituted 1,2,3,4-
Tetrahydroisoquinolines to Amides: Synthetic Applications and Mechanistic
Study
Man-Ho So, Yungen Liu, Chi-Ming Ho, and Chi-Ming Che*[a]
Abstract: Selective oxidation of amines
using oxygen as terminal oxidant is an
important area in green chemistry. In
this work, we describe the use of
graphite-supported gold nanoparticles
(AuNPs/C) to catalyze aerobic oxida-
tion of cyclic and acyclic benzylic
amines to the corresponding imines
with moderate-to-excellent substrate
conversions (43–100%) and product
yields (66–99%) (19 examples). Oxida-
tion of N-substituted 1,2,3,4-tetrahy-
droisoquinolines in the presence of
aqueous NaHCO3 solution gave the
corresponding amides in good yields
(83–93%) with high selectivity (up to
amide/enamide=93:4) (6 examples).
benzylideneACTHNGUTERN(UNG phenyl)methanamine
without significant loss of catalytic ac-
tivity and selectivity. This protocol
“AuNPs/C+O2” can be scaled to the
gram scale, and 8.9 g (84% isolated
yield) of 3,4-dihydroisoquinoline can
be obtained from the oxidation of 10 g
1,2,3,4-tetrahydroisoquinoline in a one-
pot reaction. Based on the results of ki-
netic studies, radical traps experiment,
and Hammett plot, a mechanism in-
volving the hydrogen-transfer reaction
from amine to metal and oxidation of
M-H is proposed.
The same protocol can be applied to
the synthesis of benzimidazoles from
the reaction of o-phenylenediamines
with benzaldehydes under aerobic con-
ditions (8 examples). By simple centri-
fugation, AuNPs/C can be recovered
and reused for ten consecutive runs for
the oxidation of dibenzylamine to N-
Keywords: amines · gold · hetero-
geneous catalysis · nanoparticles ·
oxidation
Introduction
nanoparticles have been reported to catalyze aerobic oxida-
tion of alcohols,[4] glucose,[5] alkenes,[6] primary amines to
amides,[7] anilines to azo compounds,[8] alcohols with amines
to imines or oximes,[9] and oxidation of CO.[10] Hydrogena-
tion of organic nitro-compounds[11] and activation of CO2
for the synthesis of disubstituted ureas and cyclic carbon-
ate[12] can also be catalyzed using solid-supported AuNPs as
catalysts. Gold-containing bimetallic nanoparticles, such as
Au–Pd nanoparticles[13] and Au–Pt nanoparticles,[14] can also
catalyze the aerobic oxidation of alcohols.
Among the transition metal-catalyzed organic transforma-
tion reactions, there has been a surge of interest in gold cat-
alysis.[1,2] Of particular interest to us is the use of gold nano-
particles (AuNPs) as catalyst. Metal nanoparticles have a
high density of active sites on the surface and usually exhibit
unique catalytic properties superior to their bulk counter-
parts,[3] and thus, are potential catalysts for organic transfor-
mation reactions with practical interest. Monometallic gold
Selective oxidation of amines is an important area in or-
ganic chemistry,[15] as the oxidation products, such as imines,
are versatile building blocks for organic synthesis (e.g.,
Mannich addition and 1,3-dipolar [2+3] cycloaddition). Stoi-
chiometric methods such as the use of hypervalent iodi-
ne(V) reagents have been successfully employed for amine
oxidations of practical interest.[16] Nevertheless, a catalytic
system utilizing oxygen as a terminal oxidant is desirable in
the context of green chemistry.[15,17,18] Mizuno,[17a,c] Muraha-
shi,[17b,g] Bꢀckvall,[17d] and Wang,[17i] have reported important
works on ruthenium-catalyzed aerobic oxidation of amines.
[a] M.-H. So, Dr. Y. Liu, Dr. C.-M. Ho, Prof. C.-M. Che
Department of Chemistry and Open Laboratory of Chemical Biology
of the Institute of Molecular Technology for Drug Discovery and
Synthesis
The University of Hong Kong
Pokfulam Road, Hong Kong SAR (China)
Fax : (+852)2857-1586
E-mail: cmche@hku.hk
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.200900261.
Chem. Asian J. 2009, 4, 1551 – 1561
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FULL PAPERS
In 2007, Angelici and co-workers reported the use of bulk
gold powder (~103 nm particle size) as catalyst for aerobic
oxidative dehydrogenation of secondary amines to imines (6
examples).[17e] Realizing that this catalytic oxidation likely
occurs on the active surface of the heterogeneous gold
powder, we conceive that AuNPs with high density of active
sites and large surface area-to-volume ratio should be a
better catalyst for the aerobic oxidation of amines. Herein is
described the use of graphite-supported 14.5 nm gold nano-
particles (AuNPs/C) as an efficient heterogeneous catalyst
for selective aerobic oxidative dehydrogenation of a diversi-
ty of benzylic amines to imines. We also report here, for the
first time, the AuNPs/C-catalyzed aerobic oxidation of N-
substituted 1,2,3,4-tetrahydroisoquinolines to amides in
good yields with high selectivity. When N-phenyl 1,2,3,4-tet-
rahydroisoquinoline is oxidized in the presence of nucleo-
lution mixture for 24 h. After centrifugation, washing with
water, and drying in an oven, the graphite-supported AuNPs
catalyst (AuNPs/C) was obtained as a black solid. The gold
loading on graphite was 0.1 mmolgꢀ1 as analyzed by induc-
tively coupled plasma-mass spectrometry (ICP-MS).[20] Ex-
amination of the AuNPs/C catalyst by powder X-ray diffrac-
tion (XRD) confirmed the presence of metallic gold on
graphite (Figure 1a). Diffraction peaks appearing at 2q=
38.238, 44.498, 64.638, 77.548, and 81.828 correspond to the
ꢀ
philes, C C bond formation products are obtained. On the
basis of the results of the kinetic isotopic effect, radical
traps experiment, and the effect of para-substituent on N-
phenylbenzylamines (Hammett plot), a mechanism involv-
ing hydrogen transfer for the oxidation of benzylic amines is
proposed. After completion of this work and during the
preparation of this manuscript, reports by Angelici,[17j]
Corma,[17k] Garcia,[17k] Baiker,[17l–n] and co-workers on the
aerobic oxidation of amines to imines catalyzed by AuNPs
supported on alumina,[17j] titania,[17k] and active carbon,[17k]
or by AuNPs in situ formed from reduction of Au-
ACHTUNGTRENNUNG
(OAc)3,[17l–n] were published.
Results and Discussion
Preparation and Characterization
We prepared two kinds of supported AuNPs catalyst by dep-
osition of the AuNPs onto graphite and hydroxyapatite
(HAP). Typically, citrate reduction of KAuCl4 salt gave a
wine-red suspension of AuNPs (12–13 nm) in water accord-
ing to Turkevishꢂs method.[19] The as-prepared AuNPs were
deposited onto graphite through vigorous stirring of the so-
Abstract in Chinese:
Figure 1. a) Powder XRD pattern, b) TEM image, c) SAED pattern, and
d) EDX spectrum of the AuNPs/C catalyst.
[111], [200], [220], [311], and [222] Miller planes of the
cubic gold, respectively (JCPDS no. 04-0784). Broadening of
these diffraction peaks is attributed to the small crystal size
of the gold nanoparticles. The structure of graphite was re-
tained after grafting of the AuNPs on its surface. As re-
vealed by transmission electron microscopy (TEM), uniform
AuNPs were deposited on the graphite surface with an aver-
age diameter and monodispersity of 14.5ꢁ1.2 nm and 8.3%,
respectively (Figure 1b). The selected-area electron diffrac-
tion (SAED) pattern revealed diffraction rings which could
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Chem. Asian J. 2009, 4, 1551 – 1561

Graphite-Supported Gold Nanoparticles as Efficient Catalyst for Aerobic Oxidation
Table 1. Aerobic oxidation of dibenzylamine catalyzed by various gold
be attributed to the ring pattern of metallic gold and of
graphite (Figure 1c). Energy-dispersive X-ray (EDX) micro-
analysis revealed the presence of Au and C peaks, further
supporting the presence of gold on graphite (Figure 1d).
We have also prepared AuNPs of smaller size (6.0ꢁ
0.5 nm) by borohydride reduction,[21] and these AuNPs were
then deposited on graphite. However, the average particle
size (8.9ꢁ2.2 nm) and size distribution (monodispersity:
25.2%) of the AuNPs increased dramatically by 48.3% after
adsorption onto the graphite surface. We have also attempt-
ed to prepare AuNPs by a polyvinylpyrrolidone-protected
method,[22] which allows better control of particle size distri-
bution, but the as prepared AuNPs failed to be deposited
onto the graphite surface. We have attempted to prepare
other solid-supported AuNPs catalysts using HAP, ZnO,
Al2O3, and SiO2 as solid supports. However, attempts to im-
mobilize 14.5 nm AuNPs on ZnO, Al2O3, and SiO2 were not
successful, as the Au contents were lower than 2.0 wt%.
Therefore, catalytic activities of these solid-supported
AuNPs catalysts were not evaluated in this work. As depict-
ed from the TEM image of the HAP-supported AuNPs
(AuNPs/HAP), uniform AuNPs were deposited on the HAP
surface (Figure 2). The average diameter and monodispersi-
catalysts.[a]
Entry
Catalyst
Run
Conv. [%][b]
Yield [%][b,c]
1
2
3
4
5
6
7
8
AuNPs/C
1
2
3
4
5
6
7
8
9
10
–
–
–
–
–
–
–
–
–
–
–
100[d]
100[d]
98[d]
98[d]
97[d]
96[d]
93[d]
86[d]
84[d]
80[d]
69[e]
100[e,f]
100
4[g]
95[d]
95[d]
97[d]
95[d]
98[d]
98[d]
94[d]
98[d]
98[d]
98[d]
95
95
95
90
86
89
66
93
85
9
10
11
12
13
14
15
16
17
18
19
20
21
AuNPs/C
AuNPs/C
AuNPs/HAP
Au powder
AuCl
55
47
4
3
KAuCl4
A
U
Au
A
A
U
2
Graphite
–
Nil[h]
Nil
–
–
[a] Reaction conditions: 1a (0.4 mmol), gold catalyst (Au: 5 mol%), tolu-
ene (8 mL), O2 bubbling, 1108C, 17 h; unless otherwise stated. [b] Con-
version and yield were determined by 1H NMR using Ph2C=CH2 as the
internal standard. [c] Yield was calculated based on substrate conversion.
[d] Conversion and yield were determined by GC-MS using naphthalene
as the internal standard. [e] Air bubbling was used instead of O2 bub-
bling. [f] Reaction time: 55 h. [g] Au powder (4.0 mg) was used.
[h] Graphite (200 mg) was used.
product yield (95%) were obtained with AuNPs/C catalyst
(Table 1; entry 1). When air was used instead of oxygen,
only 69% conversion was attained for the same reaction
time (entry 11). And a longer reaction time was needed to
achieve complete substrate conversion (55 h; entry 12).
Comparable catalytic activity and product yield were ob-
tained when AuNPs/HAP was used as the catalyst
(entry 13). Notably, the same amount of commercially avail-
able gold powder (2–5 mm; Strem Chemicals, Inc.) was
found to be catalytically inactive under the same conditions
(entry 14). AuCl and KAuCl4 were active catalysts but both
resulted in lower substrate conversions (~50%) and product
yields (86–89%; entries 15, 16), and Au0 metal was deposit-
Figure 2. TEM image of the AuNPs/HAP catalyst.
ty of the AuNPs were 14.5ꢁ1.2 nm and 8.3%, respectively.
We have also attempted to increase the loading to
0.2 mmolgꢀ1, but the result was less reproducible. As a
result, the AuNPs/C catalyst with 14.5 nm gold nanoparticles
was used in this work unless otherwise specified.
ed on the glass vial. [AuIII
ACHUTGTNRENU(NG Salen)]PF6, AuACHTUNGTRNEN(UGN PPh3)Cl, and
[AuIII
AHCTUNGTRENNUNG
tries 17–19). No substrate conversion was found with graph-
ite alone or without a catalyst (entries 20–21).
Solid-supported catalyst facilitates product separation and
can be easily recycled. For the aerobic oxidation of 1a cata-
lyzed by in situ formed AuNPs/CeO2, the conversion de-
creased from 80% to 67% upon using the catalyst for two
consecutive runs.[17n] In the case of aerobic oxidation of ben-
zylamine, using catalyst Au/Al2O3 for two consecutive runs
decreased the yield from 92% to 71%,[17j] and using in situ
formed catalyst AuNPs/CeO2/FeOx for four consecutive runs
reduced the conversion from ~50% to ~34%.[17m]
Catalytic Aerobic Oxidation of Amines
Catalyst Screening and Optimization
The catalytic activities of various gold catalysts (5 mol%)
towards the oxidation of dibenzylamine (1a) using oxygen
(1 atm, bubbling) as oxidant at 1108C were examined
(Table 1). Complete substrate conversion and excellent
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1553

C.-M. Che et al.
FULL PAPERS
Figure 3. Chemical structures of [AuIII
ACTHNUTRGENNG(U Salen)]PF6, AuACHTUNGTRNEN(UGN PPh3)Cl, and
[AuIII
ACHTUNGTRENNUNG(TPP)]Cl complexes.
As depicted in Table 1, AuNPs/C catalyst (which can be
recovered by centrifugation) was used for ten consecutive
runs without deterioration of
Figure 4. TEM image of the recycled AuNPs/C catalyst.
product yield (>94% yield; en-
tries 1–10).
A
total product
Table 2. Aerobic oxidation of secondary amines using the “AuNPs/C+O2” protocol.[a]
turnover number of 180 was ob-
tained. Only a slight decrease
in conversion from 100% to
93% was found after seven
consecutive runs. We have de-
termined the Au content in the
reaction mixture by ICP-MS.
No detectable amount of Au
was found after each run, indi-
cating that leaching of the Au
metal was insignificant. The sta-
bility of AuNPs under the reac-
tion conditions is an important
factor contributing to its cata-
lytic activities. TEM analysis of
AuNPs/C catalyst after ten re-
cycling runs showed that the
average size and monodispersi-
ty of AuNPs were slightly in-
creased from its original values
to 15.3ꢁ1.7 nm and 11.3%, re-
spectively (Figure 4), which
might account for the decrease
in substrate conversion upon re-
cycling of the catalyst.
Entry
Substrate
R1
R2
Product
Conv. [%][b]
Yield [%][b,c]
1
2
3
4
5
6
7
8
1b
1b
1b
1c
1d
1e
1 f
1g
1h
1i
OMe
OMe
OMe
Me
tBu
H
Cl
Br
NMe2
OMe
H
H
H
H
NO2
OMe
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
2b
2b
2b
2c
2d
2e
2 f
2g
100
100[d]
81[e]
100
100
100
94
95
97
95
97
98
96
99
99
88
9
Ph
2h
2i
100
100
100
100
100
100
71
95
95
10
11
12
13
14
15
16
4-MeOC6H4
G
1j
2j+2a
2k+2a
2l
2m+2a
2n+2a
2o
93 (79:14)
88 (78:10)
88
81 (58:23)
93 (48:45)
86
1k
1 L
1m
1n
1o
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
Cy
Cy
Cy
100
[a] Reaction conditions: amines (0.4 mmol), AuNPs/C (Au: 5 mol%), toluene (8 mL), O2 bubbling, 1108C,
24 h; unless otherwise stated. [b] Conversion and yield were determined by 1H NMR using Ph2C=CH2 as the
internal standard. [c] Yield was calculated based on substrate conversion. The ratio of products is shown in pa-
rentheses. [d] AuNPs/C (Au: 1 mol%), 17 h. [e] AuNPs/C (Au: 0.5 mol%), 17 h.
Oxidation of the primary benzylamines 3p and 3q gave
the imines 2p and 2q, respectively (Scheme 1). The forma-
tion of 2p and 2q probably occurred by means of the first
Oxidation of Benzylic Amines
Using the “AuNPs/C+O2” protocol, we investigated the sub-
strate scope and limitations of the catalyst (Table 2). N-phe-
nylbenzylamines 1b–i were efficiently oxidized to their cor-
responding imines 2b–i in up to 100% substrate conversion
and ꢂ95% yields (entries 1–10). The protocol was less ef-
fective towards 1 f and 1g, both bearing an electron-with-
drawing substituent (Cl or Br) at the para-position (en-
tries 7–8). For N-alkyl-N-aryl amines 1j–o, their effective
oxidation by the “AuNPs/C+O2” protocol resulted in the se-
lective formation of corresponding imines at the benzylic
position (entries 11–16).
oxidation of primary amines to imine intermediates, which
were subsequently hydrolyzed to give aldehydes and ammo-
nia. Condensation of aldehydes and starting amines gave the
Scheme 1. Aerobic oxidation of primary amines using the “AuNPs/
C+O2” protocol.
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Graphite-Supported Gold Nanoparticles as Efficient Catalyst for Aerobic Oxidation
imines (Scheme 2). No benzonitrile was detected, which is
the major product for ruthenium-catalyzed oxidation of pri-
mary amines.[17a,c,g,i]
for 24 h (entry 2, Table 3). After removal of the catalyst (by
filtration) and evaporation of the solvent, the crude product
ꢀ
5 could be directly used as a precursor for C C bond forma-
tion reactions including the fol-
lowing 1,3-dipolar [2+3] cyclo-
addition and Mannich reaction
of 5 (Scheme 3). Structurally in-
triguing 3,4-dihydroisoquinoline
derivatives 10 and 11 with high
Scheme 2. Proposed mechanism for the formation of coupled imines from primary amines.
product yields (83% yield) and
complete substrate conversions
were obtained from [RuACHTUNGTRENNUNG(p-cym-
ene)Cl2]2-catalyzed 1,3-dipolar [2+3] cycloaddition of the
Oxidation of Heterocyclic Amines
Heterocyclic secondary amines were selectively oxidized
using the “AuNPs/C+O2” protocol (Table 3). 1,2,3,4-Tetra-
hydroisoquinoline (4) was converted into 3,4-dihydroisoqui-
noline (5) in complete substrate conversion and good prod-
uct yield (86% yield, entry 1). In the case of 1,2,3,4-tetrahy-
crude imine 5 with ethyl diazoacetate (9). Crude product 5
ꢀ
could also undergo Mannich type C C bond formation with
ketones 12a–c to give 13a–c in 56-81% yields.
We have examined the oxidation of heterocyclic tertiary
amines using the “AuNPs/C+O2” protocol. Oxidation of N-
alkyl 1,2,3,4-tetrahydroisoquinoline 14a by the “AuNPs/
C+O2” protocol produced a mixture of amide 15a and en-
amide 16a in a ratio of 32:61 (entry 1, Table 4). This product
Table 3. Aerobic oxidation of heterocyclic secondary amines using the
“AuNPs/C+O2” protocol.[a]
Entry
Substrate
Product
Conv. [%][b]
Yield [%][b,c]
1
2
100
95 (86:9)
92 (84:8)
Table 4. Aerobic oxidation of tertiary amines 14 using the “AuNPs/
C+O2” protocol.[a]
100[d]
Entry
Substrate
R
Products
Conv. [%][b]
Yield [%][b,c]
3
92
95
1
2
3
4
5
6
7
8
14a
14a
14a
14b
14a
14b
14c
14d
14e
14 f
Me
Me
Me
Et
Me
Et
nPr
nBu
Octyl
Bn
15a+16a
16a
100
27
93ACHTUNGTRENNUNG
(32:61)[d]
90[e]
4
5
43
78
84
15a+16a
15b+16b
15a+16a
15b+16b
15c+16c
15d+16d
15e+16e
15 f+16 f
100
100
100
100
100
100
100
100
95 (90:5)[f]
91 (79:12)[f]
96 (92:4)
99 (93:6)
90 (85:5)
90 (83:7)
94 (88:6)
97 (93:4)
60[e]
6
68
66
9
10
[a] Reaction conditions: amines (0.4 mmol), AuNPs/C (Au: 5 mol%), tol-
uene (8 mL), O2 bubbling, 1108C, 24 h; unless otherwise stated. [b] Con-
version and yield were determined by 1H NMR using Ph2C=CH2 as the
internal standard. [c] Yield was calculated based on substrate conversion.
The ratio of products is shown in parentheses. [d] 4 (80 mmol), AuNPs/C
(Au: 3 mol%), toluene (1.6 L). [e] AuNPs/HAP (Au: 5 mol%) was used
as the catalyst.
[a] Reaction conditions: amine (0.4 mmol), AuNPs/C (Au: 5 mol%), tol-
uene (10 mL), saturated NaHCO3 aqueous solution (1 mL), O2 bubbling,
1108C, 24 h; unless otherwise stated. [b] Conversion and yield were de-
1
termined by H NMR using Ph2C=CH2 as the internal standard. [c] Yield
was calculated based on substrate conversion. The ratio of products is
shown in parentheses. [d] Without addition of saturated NaHCO3 aque-
ous solution. [e] Only anhydrous toluene (10 mL) was used as solvent
without addition of saturated NaHCO3 aqueous solution. [f] H2O (1 mL)
was used instead of saturated NaHCO3 aqueous solution.
droquinolines (7a,b) and indoline (7c), quinolines (8a,b)
and indole (8c) were obtained, respectively, in moderate to
excellent yields (entries 3, 4, 6). Using AuNPs/HAP as the
catalyst, the substrate conversion and product yield for the
oxidation of 7b to 8b could be improved to 60% and 84%,
respectively (entry 5).
ratio was subsequently tuned by the following reaction con-
ditions. Under vigorously dried conditions, only enamide
16a was obtained, albeit in low yield (entry 2). Amide 15
could be selectively obtained in good yield in the presence
of H2O (9% v/v) (entries 3 and 4). When saturated
NaHCO3 solution, instead of H2O, was added to the reaction
mixture, the ratios of 15a/16a and 15b/16b increased from
90:5 to 92:4 and 79:12 to 93:6, respectively (compare en-
tries 3 and 4 with entries 5 and 6). Prior to this work, no
In a recent report by Angelici and co-workers,[17j]
a
1.0 gram-scale aerobic oxidation of 4 catalyzed by Au/Al2O3
at 1008C for 80 h was described. Without modification of
the conditions noted in Table 3, our “AuNPs/C+O2” proto-
col could be performed on a 10 gram-scale. Oxidation of
10.7 g of 4 (80 mmol) furnished 8.9 g of 5 (84% yield) using
the “AuNPs/C+O2” protocol in a one-pot reaction at 1108C
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C.-M. Che et al.
FULL PAPERS
Synthesis of Benzimidazoles
Benzimidazole compounds are
known to exhibit a wide range
of therapeutic activities,[24] and
they are commonly synthesized
by the coupling of o-phenylene-
diamines with carboxylic acids,
or oxidative cyclo-dehydrogena-
tion of the aniline Schiff
base.[25] In a recent work by
Sharghi
porphyrinatoiron
and
co-workers,
AHCTUNGTREGUN(NN III) was used
as a catalyst for the synthesis of
benzimidazoles using oxygen as
oxidant.[25b] In this work, the
“AuNPs/C+O2” protocol could
be applied to the synthesis of
benzimidazole derivatives 27a–
h, by means of a one-pot oxida-
Scheme 3. Utilization of the 3,4-dihydroisoquinoline (5) obtained from AuNPs/C-catalyzed aerobic oxidation
of 4. When 12a was used, trifluoroacetic acid (1.5 equiv) was added after the reaction.
AuNPs catalyst had been reported to be an efficient catalyst
for the conversion of amines 14 to amides 15.
Imines and iminium cations are versatile building blocks
tive coupling reaction of o-phenylenediamine (25) with ben-
zaldehydes (26) with complete substrate conversion and
high product yields (90–99% yield; Table 6). Using the reac-
tion of 25 with 26b as an example, lowering the catalyst
loading to 1 mol% gave 27b in a satisfactory 86% yield
(entry 3).
ꢀ
for C C bond formation reactions. In recent years, Li and
co-workers have extensively studied the cross-dehydrogena-
tive coupling (CDC) reaction of tertiary amines using
copper catalysts.[17f,23] In this work, we found that when N-
phenyl tetrahydroisoquinoline (17) was oxidized by the
“AuNPs/C+O2” protocol, a cationic iminium intermediate
was generated, which could react with nucleophiles (8c, 18,
20, and 23) to give the desired products in 70–80% yields
(Table 5). Complete substrate conversion was obtained with
malonate 18 or phenylacetylene 20 as nucleophile.
Mechanism
To obtain information on the reaction mechanism, we first
examined the kinetic isotopic effect for the oxidation of N-
phenyl-a-deutero-4-methylbenzylamine (28) by the “AuNPs/
C+O2” protocol at 1108C (Scheme 4). The yield and ratio of
deuterated 29 and non-deuter-
ated 2c products were deter-
Table 5. Addition of nucleophiles to cationic iminium intermediates generated using the “AuNPs/C+O2” pro-
mined by 1H NMR using
Ph2C=CH2 as the internal stan-
dard. A moderate primary ki-
netic isotopic effect (KIE) (kH/
kD =4.9 at 1108C) was found,
tocol.[a]
Entry
Substrate
Nucleophile
Product
t [d]
Conv. [%][b]
100
Yield [%][b,c]
1
1.5
78[d]
ꢀ
indicative of C H bond cleav-
age at the benzylic position as
the rate-determining step.
2
3
2
1
100
27
80[d]
To investigate the influence
of electron-withdrawing or
electron-donating substituents
on the rate of the oxidation re-
action, a series of para-substi-
tuted N-phenylbenzylamines
were tested. Competitive oxi-
dation of p-YC6H4CH2NHPh
(Y=OMe, Me, H, Cl and CF3)
using the “AuNPs/C+O2” pro-
tocol revealed a good linear
free energy relationship (R2 =
0.99) with a negative reaction
constant (1=ꢀ2.05) (Figure 5
70
4
1
35
70
[a] Reaction conditions: 17 (0.4 mmol), nucleophile (0.8 mmol), AuNPs/C (Au: 5 mol%), toluene (8 mL), O2
bubbling, 1108C; unless otherwise stated. [b] Conversion and yield were determined by 1H NMR using Ph2C=
CH2 as the internal standard. [c] Yield was calculated based on substrate conversion. [d] In the presence of
K2CO3 (1 mmol).
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Chem. Asian J. 2009, 4, 1551 – 1561

Graphite-Supported Gold Nanoparticles as Efficient Catalyst for Aerobic Oxidation
Table 6. One-pot synthesis of benzimidazole 27 using the “AuNPs/
C+O2” protocol.[a]
Entry
1
Benzaldehyde 26
Benzimidazole 27
t [h][b]
Yield [%][c]
96
2
2
3
2
15
99
86[d]
4
5
6
7
8
3.5
2
95
93
97
94
90
Figure 5. Hammett plot (log krel vs s) for the oxidation of p-
YC6H4CH2NHPh (Y=OMe, Me, H, Cl, and CF3) using the “AuNPs/
C+O2” protocol.
“AuNPs/C+O2” protocol. No significant effect on the initial
reaction rate was noted when the oxygen partial pressure
was >0.1 atm (Figure S1 in the Supporting Information). It
should be noted that no conversion of the substrate was
found in the absence of oxygen (under argon atmosphere).
On the basis of the above results, we proposed a mecha-
nism for the AuNPs/C-catalyzed aerobic oxidation of
amines, which is depicted in Scheme 5. First, amine coordi-
3
3
3.5
nates to the surface Aud+ site. This is followed by C H
ꢀ
bond cleavage at the benzylic position as the rate-determin-
ing step. A recent report also showed that AuNPs catalyzed
aerobic alcohol oxidation involves a b-hydride shift from
carbon to gold,[4e] lending support to our hypothesis of b-hy-
drogen elimination. Lastly, oxygen acts as a hydrogen atom
acceptor, and would possibly be reduced to H2O2. The Aud+
site is regenerated, and starts another catalytic cycle.
We have not been able to detect any H2O2 in the reaction
mixture, presumably owing to
9
4
94
[a] Reaction conditions: 25 (0.4 mmol), 26 (0.4 mmol), AuNPs/C (Au:
5 mol%), toluene (10 mL), O2 bubbling, 1108C; unless otherwise stated.
[b] Completeness of the reaction was checked by 1H NMR. [c] Isolated
yield. [d] AuNPs/C (Au: 1 mol%), t=15 h.
its instability at high tempera-
ture.[27] Note that amine 1a
could also be oxidized into
imine 2a using
a “AuNPs/
C+H2O2” protocol under an
argon atmosphere, although the
substrate conversion was lower
Scheme 4. KIE on the oxidation of 28 by the “AuNPs/C+O2” protocol.
(51% conv.; Scheme 6).
To further support that hy-
and Table S1 in the Supporting Information). The negative 1
value indicated the generation of positively-charged inter-
mediates during the reaction. The involvement of radical
species is unlikely, because addition of the radical scavenger
2,6-di-tert-butyl-4-methylphenol (3 equiv to substrate) to the
reaction mixture did not perturb the substrate conversion
and product yield, revealing that the AuNPs/C-catalyzed ox-
idation is unlikely to proceed through a radical chain path-
way.[26]
drogen on the gold surface is “transferred” to an H-acceptor
(oxygen), oxygen was replaced with another H-acceptor
(imine). The H-transferability of the AuNPs/C catalyst was
demonstrated by the transfer of H from amine 1b (H-
donor) to imine 2e (H-acceptor) under anaerobic conditions
(Scheme 7). In this work, the product yield ratio of amine
1e to imine 2b was 1:1.06, revealing excellent H-transfer ef-
ficiency (94%). In the absence of the AuNPs/C catalyst, nei-
ther amine 1e nor imine 2b was detected. 1,4-Cyclohexa-
diene (H-donor) was also found to reduce imine 2e to
amine 1e (20% conv.; 99% yield), and benzene was detect-
We have studied the effect of oxygen pressure on the ini-
tial reaction rate for the oxidation of amine 1a by the
Chem. Asian J. 2009, 4, 1551 – 1561
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1557

C.-M. Che et al.
FULL PAPERS
Conclusions
Heterogeneous gold nanoparticles catalysts have shown in-
teresting oxidation of various organic compounds using
oxygen as oxidant.[4–10] Despite the extensive studies on the
catalytic activities of AuNPs, only a few types of the cata-
lysts have found study and application in the oxidation of
amines. Examples are the oxidation of amines to amides,[7]
and anilines to aromatic azo compounds by Au/TiO2.[8]
In this study, we prepared a graphite-supported AuNPs
catalyst and examined its catalytic activities. Graphite is a
stable allotrope of carbon at standard temperature and pres-
sure. It is inexpensive and readily available worldwide by
natural mining. The good electrical conductivity (106 S·mꢀ1
at ambient temperature) of graphite also enables its
common use as an electrode. Owing to the stability and
availability, graphite has been used as a solid support in het-
erogeneous catalysis for a long time.[28]
Scheme 5. Proposed mechanism of AuNPs/C-catalyzed aerobic oxidation
of amines.
The small particle size exhibited by metal nanoparticles is
important to their catalytic activity. Small particle size has a
large surface area-to-volume ratio and high density of active
sites on the particle surface. Several reviews and books have
described the utilization of
Scheme 6. Oxidation of 1a using the “AuNPs/C+H2O2” protocol.
transition metal nanoparticles
in organic transformations.[3,29]
We have recently demonstrated
the superior catalytic activities
of
hydroxyapatite-supported
and non cross-linked soluble
polystyrene supported rutheni-
um nanoparticles towards cis-
dihydroxylation and oxidative
cleavage of alkenes,[30] and car-
benoid transfer reactions,[31] re-
spectively. To illustrate the su-
periority of gold nanoparticles,
Scheme 7. H-transfer from donor 1b to acceptor 2e catalyzed by AuNPs/C under an argon atmosphere.
ed in the reaction mixture by gas chromatography-mass
spectrometry (GC-MS) (Scheme 8). Again, the involvement
the commercially available bulk gold powder (2–5 mm) was
found to show low catalytic activity on the aerobic oxidation
of dibenzylamine 1a (4% conv.; entry 14, Table 1), while
AuNPs/C showed complete substrate conversion under simi-
lar reaction conditions (entry 1, Table 1). This result is con-
sistent with the large surface area provided by the AuNPs.
Realizing the benefit from small sized metal nanoparticles,
we have attempted to prepare graphite-supported catalysts
with smaller AuNPs by the borohydride-reduction method
(6.0 nm). However, these smaller gold nanoparticles aggre-
gated upon grafting onto the graphite surface.
In summary,
a heterogeneous catalyst composed of
Scheme 8. Hydrogen transfer from donor 1,4-cyclohexadiene to acceptor
2e catalyzed by AuNPs/C under an argon atmosphere.
14.5 nm AuNPs supported on graphite has been prepared
and found to efficiently catalyze the oxidation of benzylic
amines. A variety of benzylic secondary amines (18 exam-
ples; Tables 2 and 3) could be successfully oxidized with
good-to-excellent substrate conversions and product yields.
This AuNPs/C catalyst can be recovered easily by centrifu-
gation. The “AuNPs/C+O2” protocol is applicable to the 10-
gram scale reaction, in which 8.9 g (84% yield) of 3,4-dihy-
droisoquinoline can be obtained by a one pot reaction. Re-
of radical species and the radical chain pathway is unlikely,
because the addition of the radical scavenger 2,6-di-tert-
butyl-4-methylphenol (3 equiv to substrate) to the reaction
mixture did not perturb the substrate conversion, product
yield, and H-transfer efficiency of the above reactions.[26]
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Graphite-Supported Gold Nanoparticles as Efficient Catalyst for Aerobic Oxidation
with distilled water and absolute ethanol. The final product was oven-
moval of the catalyst by filtration gave the crude imine
products, which can be directly used as building blocks in or-
ganic synthesis as demonstrated by the synthesis of structur-
ally intriguing 3,4-dihydroisoquinoline derivatives 10, 11,
and 13 (Scheme 3). Notably, oxidation of N-alkyl 1,2,3,4-tet-
rahydroisoquinolines 14 gave amides with good yields and
high selectivity (Table 4), and this catalytic oxidation has
not been reported in previous catalytic systems. Considering
the simple preparation and recycling ability of the AuNPs/C
catalyst, the application of this catalyst to organic transfor-
mation with practical interest is being pursued.
dried at 758C for an hour and stored in a desiccator for further character-
ization by TEM (Figure 2). The average particle size and monodispersity
of the deposited nanoparticles are 12.9ꢁ1.3 nm and 9.8%, respectively.
The gold loading on HAP was 0.1 mmolgꢀ1 as determined by ICP-MS.
Catalyst screening for aerobic oxidation of amine 1a: 1a (0.4 mmol) and
gold catalyst (Au: 5 mol%) were added to toluene (8 mL) in a glass tube
connected with a condenser. O2 gas (99.7% min., Hong Kong Oxygen
and Acetylene Co., Ltd.) was bubbled into the reaction mixture through
a syringe needle, which was inserted into the septum covering the tube
opening. The mixture was stirred and heated at 1108C for 17 h. The gold
catalyst was removed by filtration against celite and the organic product
was collected in the filtrate. Solvent was evaporated away under vacuum.
1
The substrate conversion and product yield were determined by H NMR
using 1,1-diphenylethylene as the internal standard. Pure product was iso-
lated by flash chromatography and identified by 1H and 13C NMR and
EI-MS.
Experimental Section
Recycling of AuNPs/C catalyst for aerobic oxidation of amine 1a: 1a
(0.4 mmol) and AuNPs/C catalyst (Au: 5 mol%) were added to toluene
(8 mL) in a glass tube connected with condenser. O2 gas (99.7% min.,
Hong Kong Oxygen and Acetylene Co., Ltd.) was bubbled into the reac-
tion mixture through a syringe needle, which was inserted into the
septum covering the tube opening. The mixture was stirred and heated at
1108C for 17 h. The AuNPs/C catalyst was removed by centrifugation
and the organic product was collected by decantation. The AuNPs/C cat-
alyst was washed 4–5 times with chloroform and dried in a 808C oven
overnight before the next recycle run. The substrate conversion and
product yield were determined by GC-MS using naphthalene as the inter-
nal standard.
Chemicals: All the chemicals (analytical reagent grade) were purchased
from Aldrich and were used as received without further purification
unless otherwise noted. KAuCl4 was purchased from Oxkem Limited.
Gold powder (2–5 micron; catalog number 93-7915) was purchased from
Strem Chemicals, Inc. Toluene (analytical reagent grade) was purchased
from TEDIA. [AuIII(Salen)]PF6,[32] [AuIII(TPP)]Cl,[33] and [Ru
ACHTUNGTRENNUNG ACHTUNRTGEUNNNG ACHTNUGTNER(NUGN p-cyme-
[34]
ne)Cl2]2 were synthesized according to the literature methods.
Instrumentation: The AuNPs/C catalyst was characterized by powder X-
ray diffraction (XRD), transmission electron microscope (TEM), selected
area electron diffraction (SAED) analysis, energy-dispersive X-ray mi-
croanalysis (EDX) and inductively coupled plasma–mass spectrometry
(ICP–MS). The powder XRD measurements were performed on
a
Aerobic oxidation of secondary and primary amines: Amine (0.4 mmol)
and AuNPs/C catalyst (Au: 5 mol%) were added to toluene (8 mL) in a
glass tube connected with condenser. O2 gas (99.7% min., Hong Kong
Oxygen and Acetylene Co., Ltd.) was bubbled into the reaction mixture
through a syringe needle, which was inserted into the septum covering
the tube opening. The mixture was stirred and heated at 1108C for 24 h.
The AuNPs/C catalyst was removed by filtration against celite and the or-
ganic product was collected in the filtrate. Solvent was evaporated away
under vacuum. The substrate conversion and product yield were deter-
mined by 1H NMR using 1,1-diphenylethylene as the internal standard.
Pure product was isolated by flash chromatography and identified by 1H
and 13C NMR and EI-MS.
Bruker D8 ADVANCE X-ray diffractometer with parallel CuKa radiation
(l=1.5406 ꢃ). The scanning rate is 0.018sꢀ1 in the 2q range from 20 to
908 and the step size is 0.058. The XRD samples were prepared by plac-
ing the catalyst on a glass slide. TEM and SAED analysis were done on
Philips Tecnai G2 20 S-TWIN with an accelerating voltage of 200 kV.
The TEM images were taken by Gatan MultiScan Camera Model 794.
The EDX analysis was performed on Oxford Instruments Inca with a
scanning range from 0 to 20 keV. The TEM samples were prepared by
dropping a drop of dispersion of the catalyst in ethanol to the formvar-
coated copper grids and then dried in vacuum desiccator. The average
particle size and monodispersity of the nanoparticles were measured
against 300 nanoparticles using DigitalMicrograph(TM) Demo 3.6.5 soft-
ware. ICP–MS was performed on an Agilent 7500a detector. The organic
products were characterized by nuclear magnetic resonance (NMR) spec-
troscopy (1H and 13C NMR) and electron-impact mass spectrometry (EI-
MS). 1H and 13C NMR spectra were recorded on Bruker DPX-300,
Avance400, or Bruker DPX-500 FT-NMR spectrometers with chemical
shifts (in ppm) relative to tetramethylsilane. Mass spectra were obtained
on a Finnigan MAT 95 mass spectrometer. Gas chromatography-mass
spectrometry (GC-MS) was performed on Agilent Technologies 6890N
gas chromatograph equipped with Agilent Technologies 5973 mass selec-
tive detector and an Agilent HP-5 (Cat. No. 19091J-433) capillary
column using helium as the carrier gas.
Aerobic oxidation of amine 4 in large scale: 4 (80 mmol) and AuNPs/C
catalyst (Au: 3 mol%) were added to toluene (1.6 L) in a two-neck
round-bottom flask with one of the necks connected with a condenser.
O2 gas (99.7% min., Hong Kong Oxygen and Acetylene Co., Ltd.) was
bubbled into the reaction mixture through a syringe needle, which was
inserted into the septum covering another neck of the round-bottom
flask. The mixture was stirred and heated at 1108C for 24 h. The AuNPs/
C catalyst was removed by filtration against celite and the organic prod-
uct was collected in the filtrate. Solvent was evaporated away under
vacuum. The substrate conversion and product yield were determined by
1H NMR using 1,1-diphenylethylene as the internal standard.
Synthesis of gold nanoparticles (AuNPs) by citrate reduction: Gold
nanoparticles were prepared according to the literature with some modi-
fications.[19] Briefly, sodium citrate (0.5 mmol) was added to a refluxing
aqueous solution of KAuCl4 (1 mm, 100 mL) with vigorous stirring. The
mixture was heated for further 15 min resulting in a wine red solution.
Aerobic oxidation of tertiary amine 14: 14 (0.4 mmol) and AuNPs/C cat-
alyst (Au: 5 mol%) were added to toluene (10 mL) in a glass tube con-
nected with a condenser. H2O (1 mL) or saturated NaHCO3 solution
(1 mL) was added to the reaction mixture. O2 gas (99.7% min., Hong
Kong Oxygen and Acetylene Co., Ltd.) was bubbled into the reaction
mixture through a syringe needle, which was inserted into the septum
covering the tube opening. For anhydrous condition, freshly-distilled an-
hydrous toluene was transferred to the reaction tube by cannula transfer
technique and the O2 gas was dried over a drying tube packed with
sodium hydroxide pellets prior to use. The mixture was stirred and
heated at 1108C for 24 h. By filtration against celite, the AuNPs/C cata-
lyst was removed and the organic product was collected in the filtrate.
Solvent was evaporated away under vacuum. The substrate conversion,
product yield, and selectivity were determined by 1H NMR using 1,1-di-
phenylethylene as the internal standard. Pure product was isolated by
Synthesis of graphite-supported gold nanoparticles (AuNPs/C) catalyst:
Graphite (1 g) was added to the freshly prepared gold nanoparticles solu-
tion and the mixture was stirred vigorously for 1 day. The AuNPs/C cata-
lyst was collected by centrifugation and washed three times with distilled
water and absolute ethanol. The final product was oven-dried at 758C for
an hour and stored in a desiccator for further characterizations by XRD
(Figure 1a), TEM (Figure 1b), SAED (Figure 1c), and EDX (Figure 1d).
Synthesis of hydroxyapatite-supported gold nanoparticles (AuNPs/HAP)
catalyst: HAP (1 g) was added to the freshly prepared gold nanoparticles
solution and the mixture was stirred vigorously for 1 day. The AuNPs/
HAP catalyst was collected by centrifugation and washed three times
1
flash chromatography and identified by H and 13C NMR and EI-MS.
Chem. Asian J. 2009, 4, 1551 – 1561
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1559

C.-M. Che et al.
FULL PAPERS
Aerobic oxidation of tertiary amine 17 with addition of nucleophiles: 17
(0.4 mmol), nucleophile (0.8 mmol) and AuNPs/C catalyst (Au: 5 mol%)
were added to toluene (8 mL) in a glass tube connected with a condens-
er. O2 gas (99.7% min., Hong Kong Oxygen and Acetylene Co., Ltd.)
was bubbled into the reaction mixture through a syringe needle, which
was inserted into the septum covering the tube opening. The mixture was
stirred and heated at 1108C for a given reaction time. The AuNPs/C cata-
lyst was removed by filtration against celite and the organic product was
collected in the filtrate. Solvent was evaporated away under vacuum. The
substrate conversion and product yield were determined by 1H NMR
using 1,1-diphenylethylene as the internal standard. Pure product was iso-
lated by flash chromatography and identified by 1H and 13C NMR and
EI-MS.
were determined by 1H NMR using 1,1-diphenylethylene as the internal
standard. The relative reactivity (krel) is calculated as below,
logðYf =YiÞ
kY
kH
krel
¼
¼
ð1Þ
logðHf =HiÞ
where Yf and Yi are the final and initial quantities of the para-substituted
N-phenylbenzylamine; Hf and Hi are the final and initial quantities of
amine 1e.
Oxidation of 1a by “AuNPs/C+H2O2” protocol: 1a (0.4 mmol) and
AuNPs/C catalyst (Au: 5 mol%) were added to a round-bottom flask
connected with a condenser. The flask was filled with argon with the
Schlenk line technique. Freshly-distilled toluene (8 mL) was transferred
to the reaction flask by syringe under argon atmosphere. Hydrogen per-
oxide (30 wt.% in H2O; 1.2 mmol) was added by syringe. The mixture
was stirred and heated at 1108C for 24 h under continuous argon flow.
The AuNPs/C catalyst was removed by filtration against celite and the or-
ganic product was collected in the filtrate. Solvent was evaporated away
under vacuum. The substrate conversion and product yield were deter-
mined by 1H NMR using 1,1-diphenylethylene as the internal standard.
One-pot synthesis of benzimidazole 27 using the “AuNPs/C+O2” proto-
col: Amine 25 (0.4 mmol), aldehyde 26 (0.4 mmol), and AuNPs/C catalyst
(Au: 5 mol%) were added to toluene (10 mL) in a glass tube connected
with a condenser. O2 gas (99.7% min., Hong Kong Oxygen and Acety-
lene Co., Ltd.) was bubbled into the reaction mixture through a syringe
needle, which was inserted into the septum covering the tube opening.
The mixture was stirred and heated at 1108C for a given reaction time.
Completeness of the reaction was checked by 1H NMR. By filtration
against celite, the AuNPs/C catalyst was removed and the organic prod-
uct was collected in the filtrate. Solvent was evaporated away under
vacuum. Pure product was isolated by flash chromatography and identi-
fied by 1H and 13C NMR and EI-MS. Product yield was calculated based
on the yield of isolated product.
H-transfer from 1b to 2e by AuNPs/C: 1b (0.3 mmol), 2e (0.1 mmol)
and AuNPs/C catalyst (Au: 5 mol% relative to substrate 1b) were added
to a round-bottom flask connected with a condenser. The flask was filled
with argon using the Schlenk line technique. Freshly-distilled toluene
(8 mL) was transferred to the reaction flask by syringe under argon at-
mosphere. The mixture was stirred and heated at 1108C for 24 h under
argon atmosphere. The AuNPs/C catalyst was removed by filtration
against celite and the organic product was collected in the filtrate. Sol-
vent was evaporated away under vacuum. The substrate conversion and
1,3-Dipolar [2+3] cycloaddition of amine 5 and EDA 9: To a solution of
crude amine 5 (0.4 mmol) and [RuACHTNUGTRENUNG(p-cymene)Cl2]2 catalyst (5 mol%) in
freshly-distilled dichloromethane (3 mL) was added dropwise a solution
of ethyl diazoacetate (0.2 mmol) in freshly-distilled dichloromethane
(2 mL) over an hour at 408C under argon atmosphere. After the addi-
tion, stirring and heating was continued until all the diazo compounds
had been consumed (2.5 h). Solvent was evaporated away under vacuum.
1
product yield were determined by H NMR using 1,1-diphenylethylene as
the internal standard. H-transfer efficiency is calculated as below,
½1eꢃ
Efficiency ¼
ꢄ 100%
ð2Þ
1
½2bꢃ
The product yield and selectivity were determined by H NMR using 1,1-
diphenylethylene as the internal standard. Pure product was isolated by
1
flash chromatography and identified by H and 13C NMR and EI-MS.
where [1e] and [2b] is the product yield of the corresponding H-acceptor
product 1e and H-donor product 2b respectively.
Mannich-type reaction of amine
5 and ketone 12: Crude amine 5
H-transfer from 1,4-cyclohexadiene to 2e by AuNPs/C: 2e (0.1 mmol)
and AuNPs/C catalyst (Au: 5 mol% relative to 1,4-cyclohexadiene) were
added to a round-bottom flask connected with condenser. The flask was
filled with argon using the Schlenk line technique. Freshly-distilled tolu-
ene (8 mL) was transferred to the reaction flask by syringe under argon
atmosphere. 1,4-Cyclohexadiene (0.4 mmol) was added to the flask under
argon atmosphere. The mixture was stirred and heated at 1108C for 24 h
under argon atmosphere. The crude reaction mixture was immediately
analyzed by GC-MS qualitatively. The AuNPs/C catalyst was removed by
filtration against celite and the organic product was collected in the fil-
trate. Solvent was evaporated away under vacuum. The substrate conver-
sion and product yield of 1e were determined by 1H NMR using 1,1-di-
phenylethylene as the internal standard.
(0.4 mmol), ketone 12 (1 mmol), and l-proline (0.4 mmol) were added to
isopropyl alcohol (1 mL) in a round-bottom flask. The mixture was
stirred at room temperature for 24 h. When ketone 12a was used, tri-
fluoroacetic acid (0.6 mmol) was added after the reaction and stirred for
a further 5 min. Most of the l-proline was removed by filtration against
silica gel and the organic product was collected in the filtrate. Solvent
was evaporated away under vacuum. The substrate conversion and prod-
uct yield were determined by 1H NMR using 1,1-diphenylethylene as the
internal standard. Pure product was isolated by flash chromatography
1
and identified by H and 13C NMR and EI-MS.
Aerobic oxidation of N-phenyl-a-deutero-4-methylbenzylamine 28: 28
(0.4 mmol) and AuNPs/C catalyst (Au: 5 mol%) were added to toluene
(8 mL) in a glass tube connected with a condenser. O2 gas (99.7% min.,
Hong Kong Oxygen and Acetylene Co., Ltd.) was bubbled into the reac-
tion mixture through a syringe needle, which was inserted into the
septum covering the tube opening. The mixture was stirred and heated at
1108C for 1 hour. The AuNPs/C catalyst was removed by filtration
against celite and the organic product was collected in the filtrate. Sol-
vent was evaporated away under vacuum. The product yield of 2c and 29
were determined by 1H NMR using 1,1-diphenylethylene as the internal
standard.
Acknowledgements
This work was supported by the Hong Kong Research Grants Council
(HKU 7009/06 and CityU 2/06C), Innovation and Technology Council
(ITS/189/08) and the University Grants Committee of the Hong Kong
SAR of China (Area of Excellence Scheme AOE/P-10/01). We thank Dr.
Raymond Wai-Yin Sun and Dr. Vanessa Kar-Yan Lo for the assistance in
the synthesis of various gold complexes. We offer our heartfelt thanks to
Mr. Frankie Yu-Fee Chan and Mr. Wing-Sang Lee of Electron Micro-
scope Unit of The University of Hong Kong for their technical assis-
tance.
Competitive oxidation of para-substituted N-phenylbenzylamines: 1e
(0.4 mmol), para-substituted N-phenylbenzylamine (0.4 mmol) and
AuNPs/C catalyst (Au: 5 mol%; 20 mmol) were added to toluene (8 mL)
in a glass tube connected with a condenser. O2 gas (99.7% min., Hong
Kong Oxygen and Acetylene Co., Ltd.) was bubbled into the reaction
mixture through a syringe needle, which was inserted into the septum
covering the tube opening. The mixture was stirred and heated at 1108C
for 1.5 h. The AuNPs/C catalyst was removed by filtration against celite
and the organic product was collected in the filtrate. Solvent was evapo-
rated away under vacuum. The substrate conversion and product yield
[1] Recent reviews: a) A. S. K. Hashmi, G. J. Hutchings, Angew. Chem.
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1560
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Chem. Asian J. 2009, 4, 1551 – 1561

Graphite-Supported Gold Nanoparticles as Efficient Catalyst for Aerobic Oxidation
b) D. J. Gorin, F. D. Toste, Nature 2007, 446, 395–403; c) A. S. K.
Hashmi, Chem. Rev. 2007, 107, 3180–3211; d) Z. Li, C. Brouwer, C.
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Received: July 14, 2009
Chem. Asian J. 2009, 4, 1551 – 1561
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1561