Highly efficient double-carbonylation of amines to oxamides using gold nanoparticle catalysts

Article abstract of DOI:10.1039/c2cc36636c

Hydrotalcite-supported gold nanoparticles (Au/HT) catalyzed the highly efficient double-carbonylation of amines to oxamides under mild reaction conditions. Various amines were selectively converted to the corresponding oxamides. The cooperation between gold nanoparticles and basic sites of HT plays a key role in the reaction.

Full text of DOI:10.1039/c2cc36636c

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Energy Chemistry, Department of Materials
Engineering Science, Graduate School of Engineering
Science, Osaka University, Japan
Highly efficient double-carbonylation of amines to oxamides
using gold nanoparticle catalysts
Supported gold nanoparticles catalyzed the double-carbonylation
of various amines to the corresponding oxamides with high
efficiency under mild reaction conditions. The cooperation between
gold nanoparticles and basic sites of supports plays a key role in the
carbonylation.
See Kiyotomi Kaneda et al.,
Chem. Commun., 2012, 48, 11733.
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COMMUNICATION
Highly efficient double-carbonylation of amines to oxamides using gold
nanoparticle catalystsw
Takato Mitsudome,a Akifumi Noujima,a Tomoo Mizugaki,a Koichiro Jitsukawaa and
Kiyotomi Kaneda*ab
Received 12th September 2012, Accepted 8th October 2012
DOI: 10.1039/c2cc36636c
Hydrotalcite-supported gold nanoparticles (Au/HT) catalyzed the
highly efficient double-carbonylation of amines to oxamides under
mild reaction conditions. Various amines were selectively converted
to the corresponding oxamides. The cooperation between gold
nanoparticles and basic sites of HT plays a key role in the reaction.
activity or selectivity. This is the first example of the use of
Au NP catalysts for the double-carbonylation of amines.
Morpholine (1) was added to acetonitrile solvent in the
presence of inorganic materials-supported Au NPs with similar
particle sizes of Au NPs and then the mixture was heated
for 24 h at 110 1C under CO/O2 (5/1 atm) (Table 1, entries 1,
7–9 and 11).5 When using Au NPs supported on basic materials
such as HT and Al2O3, 1 was converted efficiently to afford
the corresponding oxamide 1,10-oxalyldimorpholine (2) (entries
1 and 7). Notably, HT-supported Au NPs (Au/HT) showed
high catalytic activity, providing 94% yield of 2 with 99%
selectivity. On the other hand, non-basic supports such as TiO2,
hydroxyapatite (HAP) and SiO2 were not effective (entries 8,
9 and 11). The addition of Na2CO3 as a base in the ineffective
Carbonylations of nitrogen-containing compounds have attracted
much attention in both academic and industrial chemistry.1 In
this content, mono-carbonylations of amines to the corresponding
N,N0-disubstituted urea derivatives with carbon monoxide
have been achieved using various metal complex catalysts.2 On
the other hand, catalytic double-carbonylations of amines are
considerably rare despite their straightforward approach to the
synthesis of oxamides which are important precursors to carboxylic
acids and amides as well as key components of anticancer
drugs and HIV inhibitors.3 To date, there are a few homo-
geneous catalysts involving Pd or Ni complexes for the double-
carbonylation.4 These catalytic systems, however, suffer from
the requirement of a high pressure of CO (>50 atm), inorganic
halide promoters such as KI and CuI as well as stoichiometric
amounts of hazardous oxidants such as 1,4-dichloro-2-butene
and FeCl3(OPPh3)2. Tedious workup procedures for the separation
of the catalysts from the reaction mixtures and the reuse of the
catalysts are also significant drawbacks. Therefore, the develop-
ment of alternative and highly efficient catalytic systems for the
double-carbonylation of amines remains a challenging objective.
Herein, we present a new catalytic system using supported
gold nanoparticles (Au NPs) for highly efficient double-
carbonylation of amines to oxamides. Small Au NPs on basic
supports such as hydrotalcite (HT) and Al2O3 showed high
catalytic activity and selectivity for the double-carbonylation
of various amines to oxamides without any additives under a
lowered pressure of CO (5 atm) with air (1 atm). The present
supported Au catalysts were reusable without any loss of
Table 1 Double-carbonylation of 1 to the corresponding oxamide (2)a
Entry
Catalyst
d (nm)
Yieldb (%)
Sel.b (%)
1
Au/HT
Au/HT
Au/HT
Au/HT
Au/HT
Au/HT
Au/Al2O3
Au/TiO2
Au/HAP
Au/HAP
Au/SiO2
Au/HT
Au/HT
Au/HT
Au/HT
Rh/HT
Pt/HT
2.7
2.7
2.7
3.0
3.0
3.0
3.6
3.7
3.0
3.0
2.2
5.8
7.9
12
94
93
1
91
91
91
75
25
2
99
99
99
99
99
99
99
99
99
99
99
99
99
99
99
99
—
—
—
—
—
—
2c
3d
4c,e
5c,f
6c,g
7
8
9
10h
11
12
13
14
15
16
17
18
19
20
21
22
55
2
76
66
51
38
6
0
0
0
0
20
Pd/HT
a Department of Materials Engineering Science, Graduate School of
Engineering Science, Osaka University, 1-3 Machikaneyama,
Toyonaka, Osaka, 560-8531, Japan.
E-mail: kaneda@cheng.es.osaka-u.ac.jp; Fax: +81 6-6850-6260;
Tel: +81 6-6850-6260
Ru/HT
Ag/HT
PdCl2
o1
Pd(OAc)2
o1
b Research Center for Solar Energy Chemistry, Osaka University, 1-3
Machikaneyama, Toyonaka, Osaka, 560-8531, Japan
w Electronic supplementary information (ESI) available: Experimental
details, EXAFS analysis, TEM images, kinetic studies and FT-IR
spectra. See DOI: 10.1039/c2cc36636c
a
Reaction conditions: catalyst (M: 0.9 mol%), CH3CN (5 mL), 1
b
(0.5 mmol). Determined by GC using an internal standard techni-
c
que. Using 1 atm of air in place of pure O2. In the absence of O2.
d
e
f
Reuse 1. Reuse 2. Reuse 3. 1.5 mmol of Na2CO3 was added.
g
h
c
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Chem. Commun., 2012, 48, 11733–11735 11733

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HAP-supported Au NP catalyst system significantly enhanced
the yield of 2, confirming the necessity of bases for promoting
the reaction (entries 9 vs. 10). The double-carbonylation of
1 successfully proceeded even when using 1 atm of air in place
of pure O2 (entry 2).6 O2 was found to be essential; when O2 was
absent, Au/HT produced only a trace amount of 2 (entry 3).
The size effect of Au NPs was also investigated using Au/HTs
with different particle sizes (entries 1 and 12–15).7 The yields of
2 increased with decreasing particle sizes, indicating that small
Au NPs were more effective for the high catalytic activity. The
highest yield of 2 was obtained by the use of Au/HT with a
mean diameter of 2.7 nm (entry 1). Next, various metal NPs on
HT were synthesized and tested in the reaction under similar
conditions. Only Rh/HT gave a low yield of 2 (Entry 16), while
other metal NPs such as Pt, Pd, Ru and Ag did not show
any catalytic activities (entries 17–20).8 It has been reported
Table 2 Double-carbonylation of various amines to oxamidesa
Substrate
Product
Entry
Time (h) Yieldb (%) Sel.b (%)
1
2
Me2NH
Et2NH
(Me2NCO)2 12
(Et2NCO)2 12
73
87
99
99
3
4
12
12
92
87
99
99
5c
6c
7c
24
24
24
80
87
86
99
99
99
4e
that homogeneous catalytic systems such as PdCl2 and
Pd(OAc)2/K2CO3/KI4c promoted the double-carbonylation of
amines. However, the use of PdCl2 and Pd(OAc)2 in place of
Au/HT in our reaction system resulted in the formation of only
trace amounts of 2 (entries 21 and 22). These results clearly
reveal that Au NPs have unique and significantly superior
catalytic activity compared to those of other metal NPs, and
that the combination of Au NPs and bases in the presence of O2
is vital for the efficient double-carbonylation. In a separate
experiment, we carried out CO oxidation under the conditions
similar to those given in entry 2 in the absence of 1. Only 0.2%
yield of CO2 based on initial amounts of CO was obtained.9
This result shows both CO and O2 are high-selectively used for
the oxidative double-carbonylation, which is consistent with the
high efficiency of our Au/HT catalyst system.
8
24
24
24
24
85
90
93
85
99
99
99
99
9
10
11c
At 40% conversion of 1, Au/HT was removed by filtration
and further treatment of the resulting filtrate under similar
reaction conditions did not afford any products. The absence
of Au ions in the filtrate was also confirmed by inductively
coupled plasma analysis (the detection limit is below 0.1 ppm).10
These phenomena demonstrate that the double-carbonylation
takes place on the Au/HT solid surface. Kinetic studies also
support heterogeneous catalysis in the double-carbonylation
(vide infra). Furthermore, after the reaction, Au/HT was easily
recoverable by filtration from the reaction mixture and reusable
without any loss of efficiency (Table 1, entries 4–6). TEM analysis
of the used Au/HT catalyst revealed that the size of the Au NPs
did not significantly differ from those of the fresh Au/HT (Fig. S2,
ESIw), supporting the above excellent reusability of Au/HT.
Under the optimized conditions using Au/HT, the substrate
scope of amines was investigated (Table 2). Aliphatic and alicyclic
secondary amines were converted to the corresponding oxamides
in high yields with excellent selectivities (entries 1–11). Diverse
functional groups on the amines such as ether, acetal, amine and
allyl groups were compatible under the present reaction conditions.
Primary aliphatic and benzylic amines were not suitable
for the double-carbonylation; the corresponding imines were
mainly formed (entries 12 and 13). Interestingly, when
2-methyl- and 4-ethyl-piperidines were used as a mixture of
substrates, 4-ethyl piperidine reacted exclusively to afford the
corresponding double-carbonyl compound in an excellent
yield while 2-methyl piperidine remained intact. The above
phenomenon is in sharp contrast with the result obtained using
12
13
12
12
43
49
81
99
a
Reaction conditions: Au/HT (0.1 g), amine (0.5 mmol), CH3CN
b
(5 mL). Determined by GC using an internal standard technique.
c
Amine (0.2 mmol).
previously reported homogeneous catalyst Pd(OAc)2 where a
mixture of symmetric and asymmetric double-carbonylation
products was formed (Scheme 1). These differences can be
explained by the specific property of the solid catalysis; the
steric hindrance by the substituent on the ortho position of
piperidine prevents the coordination of the N atom to Au/HT.
Scheme 1 Competitive reaction of 2-methyl- and 4-ethyl-piperidine.
Scheme 2 10 mmol-scale double-carbonylation of 1 using Au/HT.
c
11734 Chem. Commun., 2012, 48, 11733–11735
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Scheme 3 Plausible reaction mechanism.
Au/HT was also applicable to scale-up conditions
(Scheme 2). Lowering the catalyst loading to 0.02 mol% gave
a turnover frequency (TOF) of 45 hꢀ1 and a turnover number
(TON) of 4500 upon prolonged heating at elevated tempe-
ratures, which demonstrated the high activity and stability of
Au/HT. These values for TOF and TON of Au/HT are much
greater than those of previously reported catalytic systems
Supports of this work were provided by JSPS KAKENHI
(23686116 and 10J01438). We thank Dr Uruga and Dr Nitta
(SPring-8) for XAFS measurements. The TEM experiments
were carried out at a facility of the Research Center for
Ultrahigh Voltage Electron Microscopy, Osaka University.
Notes and references
such as PdCl2(PPh3)2/1,4-dichloro-2-butene:4a TOF = 11 hꢀ1
,
TON = 192; Pd(OAc)2/K2CO3/KI:4c TOF = 5 hꢀ1, TON = 15;
PdCl2:4e TOF = 0.3 hꢀ1, TON = 7; PdCl2(MeCN)2/CuI/O2:4d
TOF = 0.44 hꢀ1, TON = 8.8; NiBr2(NH2Bu)4/FeCl3(OPPh3)2:4b
TOF = 2 hꢀ1, TON = 12.
1 (a) R. Skoda-Foldes, in ‘‘Modern Carbonylation Methods’’, ed.
¨
L. Kollar, Wiley-VCH, Weinheim, 2008, pp. 301–320; (b) W. Bertleff,
´
‘‘Carbonylation’’ in Ullmann’s Encyclopedia of Industrial Chemistry,
Wiley-VCH, Weinheim, 2003, DOI: 10.1002/14356007.a05 217;
(c) S. Cenini, M. Pizzotti and C. Crotti, in ‘‘Aspects of Homogeneous
Catalysis’’, ed. R. Ugo, D. Reidel, Dordrecht, 1987, vol. 6.
To obtain insight into the Au/HT-catalyzed double-carbony-
lation, the dependency of reaction rates in the double-carbony-
lation of 1 was investigated.11 The initial rates (R0) were linearly
proportional to the amount of Au/HT and independent of the
O2 pressure. The R0 increased with increasing CO pressure and
concentration of 1, and approached an asymptotic plateau at
high pressures and high concentrations, respectively, suggesting
that the reaction proceeds through the Langmuir–Hinshelwood
mechanism. A small kinetic isotope effect (kH/kD = 1.2) was
observed in the double-carbonylation of 1-(D)-morpholine.
Fourier transform infrared (FT-IR) studies of Au/HT were
also carried out. When Au/HT was treated with 1-(H)- and
1-(D)-morpholine vapor at 353 K, new bands appeared at 3234
and 2512 cmꢀ1, corresponding to the O–H and O–D stretching
bands of Mg–O(H-morpholine)–Al and Mg–O(D-morpholine)–Al,
respectively, on the surface of HT. This reveals the activation of
morpholine by the strong adsorption on basic sites of HT.11
Based on the above results, a plausible reaction mechanism is
proposed as shown in Scheme 3. First, CO is adsorbed on Au
NPs on HT (I). Next, a H atom on the N–H group of an amine
(R2NH) is withdrawn by a basic site of HT to promote the
nucleophilic attack of the R2Ndꢀ to the CO adsorbed on Au
NPs (II),12 affording the formation of H+ and [Au-CONR2]ꢀ
species (III). Subsequent coupling of [Au-CONR2]ꢀ species
occurs to produce an oxamide [(CONR2)2] accompanied by
negatively charged Au NPs and H+ (IV). The resulting hydrogen
species are treated by O2 to afford H2O, thereby completing the
catalytic cycle (V). The results obtained from our kinetic experi-
ments also support the above mechanism.13
2 (a) F. Ragaini, Dalton Trans., 2009, 6251; (b) D. J. Dıaz,
´
A. K. Darko and L. M. White, Eur. J. Org. Chem., 2007, 4453;
(c) F. Bigi, R. Maggi and G. Sartori, Green Chem., 2000, 2, 140.
3 (a) C. Aubry, A. J. Wilson, D. Emmerson, E. Murphy, Y. Y. Chan,
M. P. Dickens, M. D. Garcia, P. R. Jenkins, S. Mahale and
B. Chaudhuri, Bioorg. Med. Chem., 2009, 17, 6073; (b) M. Medou,
G. Priem, G. Quelever, M. Camplo and J. K. Kraus, Tetrahedron
Lett., 1998, 39, 4021; (c) T. Kitagawa, H. Kuroda, H. Sasaki and
K. Kawasaki, Chem. Pharm. Bull., 1987, 35, 4294.
4 (a) K. Hiwatari, Y. Kayaki, K. Okita, T. Ukai, I. Shimizu and
A. Yamamoto, Bull. Chem. Soc. Jpn., 2004, 77, 2237;
(b) P. Giannoccaro, C. F. Nobile, P. Mastrorilli and N. Ravasio,
J. Organomet. Chem., 1991, 419, 251; (c) I. P. Bar and H. Alper, Can.
J. Chem., 1990, 68, 1544; (d) S.-I. Murahashi, Y. Mitsue and K. Ike,
J. Chem. Soc., Chem. Commun., 1987, 125; (e) J. Tsuji and N. Iwamoto,
Chem. Commun., 1966, 380.
5 Au NPs on various supports were synthesized by our previously
reported method. See: T. Mitsudome, A. Noujima, T. Mizugaki,
K. Jitsukawa and K. Kaneda, Green Chem., 2009, 11, 793.
6 The flammability range of CO in air is 13.5–73.0% at 200 1C. See:
C. M. Bartish and G. M. Drissel, ‘‘Carbon monoxide’’ in Kirk-
Othmer Encyclopedia of Chemical Technology, Wiley, New York,
3rd edn, 1984, vol. 4, p. 774. The concentration of CO (83%) in
air under our reaction conditions (CO (5 atm) and air (1 atm) at
110 1C) is out of the flammability range, showing the practical
advantage of the present Au/HT catalytic system.
7 Au/HTs with different particle sizes were prepared by our previously
reported method. See: A. Noujima, T. Mitsudome, T. Mizugaki,
K. Jitsukawa and K. Kaneda, Angew. Chem., Int. Ed., 2011, 50, 2986.
8 The preparation of Pt/HT, Pd/HT, Rh/HT, Ag/HT, and Ru/HT
was reported in our previous study. See: T. Mitsudome,
A. Noujima, Y. Mikami, T. Mizugaki, K. Jitsukawa and
K. Kaneda, Chem.–Eur. J., 2010, 16, 11818.
9 For Au NPs-catalyzed CO oxidation, see: (a) M. Haruta, T. Kobayashi,
H. Sano and N. Yamada, Chem. Lett., 1987, 405; (b) A. S. K. Hashmi
and G. J. Hutchings, Angew. Chem., Int. Ed., 2006, 45, 7896.
10 For a recent report of ICP measurements being crucial for gold catalysis,
In conclusion, we discovered a highly efficient double-carbony-
lation of amines to the corresponding oxamides using Au NPs
without any additives under mild reaction conditions. Au/HT
showed outstanding catalytic activity compared to those of other
metal NPs and previously reported catalyst systems. Furthermore,
the solid Au/HT catalyst was recoverable and reusable without
any loss of its activity or selectivity. The experimental results
combined with kinetic and spectroscopic studies also establish that
Au NPs and basic supports promote the double-carbonylation in
a concerted fashion.
+
+
see: A. S. K. Hashmi, C. Lothschutz, R. Dopp, M. Ackermann, J. De
Buck Becker, M. Rudolph, C. Scholz and F. Rominger, Adv. Synth.
Catal., 2012, 354, 133.
11 See ESIw for details.
12 It has been known that solid bases abstract H atoms from amines
on their basic sites to catalyze the addition of amines to dienes. See:
(a) Y. Kakuno and H. Hattori, J. Catal., 1984, 85, 509;
(b) H. Hattori, Appl. Catal., A, 2001, 222, 247.
13 The proposed mechanism agreed well with the kinetic data show-
ing that the rate-determining step is coupling of the carbamoyl
species adsorbed on Au NPs (III -IV in Scheme 3). See ESIw for
details.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 11733–11735 11735