Selective cross-coupling of amines by alumina-supported palladium nanocluster catalysts

Article abstract of DOI:10.1039/c1gc15835j

Al₂O₃-supported Pd nanoclusters with an average particle size of 1.8 nm act as a reusable catalyst for the selective cross-coupling of amines. The reaction is a structure-sensitive reaction, demanding coordinatively unsaturated Pd atoms on a metallic nanocluster. The support also affects the activity, an amphoteric oxide (Al₂O ₃) is most effective. The Royal Society of Chemistry.

Full text of DOI:10.1039/c1gc15835j

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Green Chemistry
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COMMUNICATION
Selective cross-coupling of amines by alumina-supported palladium
nanocluster catalysts†
Ken-ichi Shimizu,*a Katsuya Shimura,*a Keiichiro Ohshima,b Masazumi Tamurab and Atsushi Satsumab
Received 12th July 2011, Accepted 19th August 2011
DOI: 10.1039/c1gc15835j
Al2O3-supported Pd nanoclusters with an average particle
size of 1.8 nm act as a reusable catalyst for the selective cross-
coupling of amines. The reaction is a structure-sensitive
reaction, demanding coordinatively unsaturated Pd atoms
on a metallic nanocluster. The support also affects the
activity, an amphoteric oxide (Al2O3) is most effective.
auto-transfer) mechanism.14–18 The process begins with the
dehydrogenation of an alkylamine to the corresponding imine.
The imine undergoes addition of another nucleophilic amine
and elimination of ammonia to form an N-alkyl imine, which
is hydrogenated by an in situ formed hydride species to the
secondary amine product. Ru15,16 and Ir17,18 complexes are
successful catalytic systems for selective amine cross-coupling
of different amines, leaving ammonia as the only by-product.
The [Cp*IrI2] complex developed by Williams and co-workers18
is of particular importance as the first example of selective
amine alkylation when both of the amines are capable of
undergoing oxidation to imines. From the environmental and
economic viewpoints, it is preferable to accomplish the se-
lective cross-coupling reaction using reusable heterogeneous
catalysts. There are many reports of heterogeneous catalysis for
the self-14,23–25 and cross-coupling6,7,14,19–22 of amines. However,
previous examples of cross-coupling reactions suffer from low
selectivity for cross-coupling different amines,22 reusability,6
low turnover number (TON), and the need for stoichiometric
amounts of additives21 or special reaction methods (microwave
heating,7,21 electrocatalysis19 and photocatalysis20). Recently, a
Pd/C-catalyzed cross-coupling reaction was reported as the first
example of a reusable heterogeneous catalyst for this reaction,
but the system requires microwave heating.7 In addition, there
are no systematic reports on the effects of metal particle size and
nature of supports on the catalytic activity.
We report herein that g-alumina-supported Pd nanoclusters
act as reusable heterogeneous catalysts for amine cross-coupling
reactions. To establish the structure–activity relationship, the
effects of the Pd particle size, support basicity (acidity) and
nature of transition metals on turnover frequency (TOF)
(defined as the activity per unit of exposed Pd surface), are
examined, and a design concept of the supported Pd metal
catalyst for the present reaction is discussed.
Supported Pd catalysts were prepared by the impregnation
method, followed by calcination and by H2-reduction. To control
the metal particle size, temperatures of calcination (Tcal) and
reduction (TH2) were changed (Table 1). The catalysts are
designated as Mx/Al2O3-D, where x is the content (wt%) of
metal (M) and D is the metal particle sizes (nm). Pd1/Al2O3-1.8
is the standard catalyst.
Supported metal nanoparticles or nanoclusters play an im-
portant role in many heterogeneous catalytic reactions for
green organic synthesis.1–3 Current interest is focused on the
development of supported metal catalysts for multi-step organic
reactions, which provide a key technology for the green synthesis
of fine chemicals.1–7 Supported Pd metal catalysts have been
widely used in organic reactions such as hydrogenation,8,9
selective oxidation,1,10,11 and multi-step one-pot reactions.5–7 To
be able to move towards a rational design for heterogeneous
synthetic catalysts, we need to understand the factors that affect
the catalytic performance of Pd catalysts. Previous work has
demonstrated that the size and support material have strong
influence over the catalytic properties of Pd, but most of these
fundamental attempts were focused on conventional reactions
such as hydrogenation8,9 and selective oxidation.10,11 To establish
a concept for the rational design of multi-functional Pd catalysts,
a systematic study of the structure–activity relationship in Pd
catalyzed one-pot organic reactions should be carried out.
However, such fundamental information is not known to the
degree necessary to design a new multi-functional heterogeneous
Pd catalyst.
Amines are intermediates and products of enormous im-
portance for chemical and life science applications. In addi-
tion to the well established Pd-catalyzed aminations of aryl
halides12 and the metal-catalyzed amination of alcohols,13,14 the
transition-metal-catalyzed alkylation of amines by amines is
an attractive alternative method of alkylamine synthesis.6,7,14–22
The reaction proceeds through a hydrogen-borrowing (hydrogen
aCatalysis Research Center, Hokkaido University, N-21, W-10, Sapporo,
001-0021, Japan. E-mail: kshimizu@cat.hokudai.ac.jp;
Fax: +81-11-706-9163; Tel: +81-11-706-9240
bDepartment of Molecular Design and Engineering, Graduate School of
Engineering, Nagoya University, Nagoya, 464-8603, Japan
As a first screening, we examined the N-alkylation of mor-
pholine (2a) with benzyl amine (1a) using various transition
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c1gc15835j
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Table 1 List of catalysts
atoms estimated by CO adsorption. The yield of 3a and TOF
depended strongly on the nature of the transition metals, support
materials, and Pd particle size. Among various transition metal
nanoclusters (Pd, Ag, Au, Pt, Rh, Ru) supported on Al2O3 (Table
2, entries 1,17–21) with similar metal particle size (0.9–2.3 nm),
Pd1/Al2O3-1.8 showed the highest 3a yield and TOF. Among
the Pd catalysts (Table 2, entries 2, 9–13) with similar size (2.4–
4.9 nm), but with different support materials (Al2O3, CeO2,
MgO, ZrO2, SiO2, C), Pd1/Al2O3-4.2 was the most effective
in terms of 3a yield and TOF. As shown in Table 1, we prepared
a series of Pd/Al2O3 catalysts with different Pd particle size.
The catalytic results (Table 2, entries 1–4) showed that the
Pd/Al2O3 catalyst with the smallest Pd size, Pd1/Al2O3-1.8,
was the best catalyst. Consequently, Pd1/Al2O3-1.8 was found
to be the most effective catalyst. In the literature, there are
two examples of heterogeneous Pd catalysts for cross-coupling
reactions of amines using Pd black6 and Pd/C.7 Table 2 shows
that Pd1/Al2O3-1.8 is more efficient than commercially available
Pd black and Pd/C in terms of activity (TOF) and selectivity
for cross-coupling.
Catalysts-xa
M/wt%
T
cal/◦Cb
T
H2/◦Cc
D/nma
Pd1/Al2O3-1.8
Pd1/Al2O3-4.2
Pd5/Al2O3-8.7
Pd5/Al2O3-15
Pd1/CeO2-2.4
Pd1/MgO-4.0
Pd1/ZrO2-4.6
Pd1/SiO2-4.9
Pd5/C-3.3
1
1
5
5
1
1
1
1
5
100
5
1
5
5
5
500
700
800
1000
700
600
500
500
—
200
500
500
500
500
500
300
400
300
100
300
—
1.8
4.2
8.7
15.2
2.4
4.0
4.6
4.9
3.3
22.7
0.9d
2.3e
1.2
1.9
1.9
Pd black
—
Ag5/Al2O3-0.9
Au1/Al2O3-2.3
Pt5/Al2O3-1.2
Rh5/Al2O3-1.9
Ru5/Al2O3-1.9
600
300
500
500
500
500
300
300
a Average particle size (nm) of supported metal estimated from CO
adsorption experiments. b Temperature of calcination. c Temperature of
reduction in H2. d Size of the Ag particle was estimated from EXAFS in
our previous study.4 e Size of the Au particle was estimated from TEM
in our previous study.29
Next, we examined reactions of benzylic amines with various
cyclic amines using Pd1/Al2O3-1.8 (Table 3, entries 1–12). p-
Substituted benzyl amines with electron-donating substituents
(Table 3, entries 2–3) proceeded with good yields, while those
with an electron-withdrawing substituent were not successful
(Table 3, entry 4). An aliphatic primary amine (Table 3, entry 6)
was also tolerated. The catalyst was applicable to heterocyclic
amines containing an oxygen or nitrogen atom (Table 3, entries
7–8). The reaction of benzyl amine 1a with various cyclic
secondary amines leads to the formation of the corresponding
N-alkylated amines in good to moderate yields (Table 3, entries
9–12). The catalyst was also applicable to the selective mono-
N-alkylation of 4-methoxyaniline using di-iso-propylamine
metal-based heterogeneous catalysts (Table 2). For the
Pd1/Al2O3-1.8 catalyst, benzyl amine (1a) was selectively con-
verted to N-benzyl-morpholine (3a) as a desired product with
88% yield, while the total yield of byproducts was 12%. In
contrast, for other catalysts such as Pd1/SiO2-4.9, benzyl amine,
(1a) was not only converted to 3a but also various byproducts.
The self coupling of 1a gave N-benzylidenebenzylamine (5a)
and its hydrogenation product, dibenzylamine (4a). Toluene
(6a) was also produced by elimination of NH3 from 1a. The
rate of 3a formation was also measured under the conditions
where conversion of aniline was below 40%, and TOF was
calculated using the rate and the number of surface metal
Table 2 Reaction of 1a with 2a by various catalystsa
Entry
Catalysts-x
1a conv. (%)
3a yield (%)
4a yield (%)
5a yield (%)
6a yield (%)
TOF/h
1
2
3
4
Pd1/Al2O3-1.8
Pd1/Al2O3-4.2
Pd5/Al2O3-8.7
Pd5/Al2O3-15
Pd1/CeO2-2.4
Pd1/MgO-4.0
Pd1/ZrO2-4.6
Pd1/SiO2-4.9
Pd5/C-3.3
100
100
64
18
73
89
100
100
100
38
26
23
6
88
80
32
5
32
50
57
41
74
12
3
2
0
0
21
17
20
4
3
0
4
4
2
8
11
2
0
4
7
5
14
1
5
8
4
0
0
4
5
3
610
460
290
170
120
290
330
340
315
74
—
—
0
0
14
4
19
19
21
26
5
3
3
3
0
9
9
10
11
12
13
14
15
16
17
18
19
20
21
8.5
16.3
16.4
13.4
7.6
9.8
8.7
3.3
3.9
5.2
4.0
6.8
Pd black
PdO
Pd(CH3COO)2
Ag5/Al2O3-0.9
Au1/Al2O3-2.3
Pt5/Al2O3-1.2
Rh5/Al2O3-1.9
Ru5/Al2O3-1.9
6
0
0
0
0
31
26
34
11
15
19
a Conversion of 1a and yields were determined by GC. TOF calculated using the number of surface metal atoms and the rate of 3a formation measured
under the conditions where conversions were below 40%.
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Table 3 Cross-coupling of amines by Pd1/Al2O3-1.8a
Yield (%)
Entry
1
1
2
Product
Conv. (%)
100
3
4
5
88
85
88
4
0
2
3
100
100
5
3
4
3
4
5
100
100
44
76
5
8
6
9
6
7
100
100
79
78
4
9
11
6
8
94
72
81
8
6
13
2
9b
100
10b
11b
100
100
72
78
11
5
6
9
12b
100
78
66
71
76
16
—
—
10
—
—
13c,d
14d,e
100
a Conversion of 1 and yields were determined by GC. b T = 125 ◦C. c t = 20 h. d 1/2 = 2 mmol/1 mmol. Yield of 3 is based on 2. e Tertiary amine (18%
yield) was also produced.
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(Table 3, entry 13) and triethylamine (Table 3, entry 14) as
alkylation reagents.
After the reaction of 1a and 2a (Table 3, entry 1), the catalyst
was easily separated from the reaction mixture by centrifugation.
ICP analysis of the filtrate confirmed that the contents of Pd
in the solution were below the detection limit (<0.1 ppm).
The separated catalyst was washed with acetone (5 mL) and
◦
distilled water (5 mL), followed by calcining at 500 C for 1 h,
and by reducing in H2 at 200 ◦C for 10 min. The recovered
catalyst showed a high yield of 3a in the first (86%) and the
second (85%) recycle tests. The total turnover number (TON)
based on total Pd reached 261, which is higher than that of a
homogeneous Ir catalyst (TON = 98) for a similar reaction.18
The above results clearly demonstrate that Pd1/Al2O3-1.8
is a highly efficient heterogeneous catalyst for the present
reaction.
Fig. 2 TOF based on the number of surface Pd atoms for the reaction
of 1a with 2a vs. average particle size of Pd in Pd/Al2O3 (Table 2, entries
1–4).
As previously proposed by Murahashi et al.6 for the Pd
black catalysed amine cross-coupling, it is most probable that
the present amine cross-coupling reaction proceeds through the
hydrogen borrowing pathway (Fig. 1), in which the reaction is
initiated by temporary removal of hydrogen from benzyl amine
1a to generate a benzyl imine 1a¢ and Pd–H species. For the
reaction of p-substituted benzyl amines with 2a by Pd1/Al2O3-
1.8, the reaction rate decreased with an increase in the Brown–
cleavage than the flat Pd (111) surface.26 To discuss the role of the
support in the Pd catalyzed reaction of 1a and 2a, we prepared
a series of supported Pd catalysts with the same Pd content
(1 wt%) and similar particle size (2.4–4.9 nm), but with a variety
of supports. It is established that the O 1s binding energy (BE)
of metal oxides decreases with an increase in the basicity of the
metal oxide.27 In Fig. 3, TOF is plotted as a function of the O 1s
BE of the support oxides. There is a volcano-type relationship
between TOF and O 1s BE, and Al2O3 as an amphoteric oxide
gives the highest activity. A possible explanation of the support
dependent activity is based on a metal-support bi-functional
mechanism, where acid–base sites on the support take part in
a certain step of the catalytic cycle. Basic sites on the support
may play a role in the C–H abstraction of 1a, and acid sites may
be effective in the polarization of the C N bond of iminium
cations and thus may promote hydrogenation of imines. Another
possibility is the electronic effect of supports on the electronic
state of Pd clusters. Recently, Raybaud et al. reported a DFT
study on the metal-support interactions at the interface of a
Pd13 cluster and g-Al2O3 and showed that the Pd metal atoms
interacting with hydroxyls on the support became positively
charged, whereas the other Pd atoms located further from the
interface were nucleophilic centers.28 This polarized nature of Pd
atoms may be effective in the C–H bond cleavage of 1a, leading
to the high activity of the Al2O3-supported Pd catalyst.
+
Okamoto parameter (s ) in the order of CH3O > CH3 > H >
+
CF3. The relationship between log(kX/kH) and s (Fig. S1 in
the ESI†) gives a fairly good straight line (r2 = 0.94) with a
+
negative slope (r = -0.52), indicating that a transition state of
the rate-determining step involves a positive charge at the a-
carbon atom adjacent to the phenyl ring. Since an induction
period was not observed in the course of 3a formation (Fig.
S2†), the hydrogenation of 3a¢ to 3a is not a slow step. Thus, it
is suggested that the C–H cleavage of 1a by Pd to produce Cd+
and Pd–Hd- species is the rate-determining step in the present
reaction.
Fig. 1 A possible reaction mechanism.
Finally, we discuss a structure–activity relationship. In Fig.
2, the TOF based on the number of surface metal atoms (from
entries 1–4 in Table 2) are plotted as a function of Pd particle size
in Pd/Al2O3. In a size range of 1.8–15.2 nm, the TOF decreases
with the particle size, indicating that the present reaction
is a structure-sensitive reaction demanding a coordinatively
unsaturated Pd site. The unsaturated Pd sites should play an
important role in the rate-determining C–H dissociation of 1a.
This result is consistent with the theoretical study by Liu and
Hu; the stepped surface of Pd clusters, containing coordinatively
unsaturated Pd, has a lower dissociation barrier in C–H bond
Fig. 3 Effect of the O 1s binding energy of oxygen atoms in the supports
on the catalytic activity of Pd catalysts with similar metal particle size
(nm) shown in parentheses.
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11 C. M. A. Parlett, D. W. Bruce, N. S. Hondow, A. F. Lee and K.
Wilson, ACS Catal., 2011, 1, 636–640.
Conclusions
12 D. Maiti, B. P. Fors, J. L. Henderson, Y. Nakamura and S. L.
Buchwald,, Chem. Sci., 2011, 2, 57–68.
Al2O3-supported Pd nanoclusters with an average particle size
of 1.8 nm act as a heterogeneous catalyst for the cross-coupling
of amines, providing the first example of a reusable Pd catalyst
for cross-coupling of amines both of which are able to undergo
dehydrogenation. The reaction is a structure-sensitive reaction,
demanding coordinatively unsaturated Pd atoms on the metallic
nanocluster. The support also affects the activity, and the
amphoteric oxide (Al2O3) gives the highest activity.
13 T. D. Nixon, M. K. Whittlesey and J. M. J. Williams, Dalton Trans.,
2009, 38, 753–762.
14 G. Guillena, D. J. Ramon and M. Yus, Chem. Rev., 2010, 110, 1611–
1641.
15 D. Hollmann, S. Bahn, A. Tillack and M. Beller, Angew. Chem., Int.
Ed., 2007, 46, 8291–8294.
16 D. Hollmann, S. Bahn, A. Tillack and M. Beller, Chem. Commun.,
2008, 44, 3199–3201.
17 A. Prades, R. Corberan, M. Poyatos and E. Peris, Chem.–Eur. J.,
2008, 14, 11474–11479.
18 O. Saidi, A. J. Blacker, M. M. Farah, S. P. Marsden and J. M. J.
Williams, Angew. Chem., Int. Ed., 2009, 48, 7375–7378.
19 M. Largeron and M.-B. Fleury, Org. Lett., 2009, 11, 883–886.
20 S.-I. Nishimoto, B. Ohtani, T. Yoshikawa and T. Kagiya, J. Am.
Chem. Soc., 1983, 105, 7180–7182.
21 A. Miyazawa, K. Saitou, K. Tanaka, T. M. Ga¨dda, M. Tashiro, G.
K. S. Prakash and G. A. Olah, Tetrahedron Lett., 2006, 47, 1437–
1439.
22 N. Sivasankar and R. Prins, J. Catal., 2006, 241, 342–355.
23 T. Ishida, N. Kawakita, T. Akita and M. Haruta, Gold Bull., 2009,
42, 267–274.
24 B. Zhu, M. Lazar, B. G. Trewyn and R. J. Angelici, J. Catal., 2008,
260, 1–6.
References
1 K. Kaneda and T. Mizugaki, Energy Environ. Sci., 2009, 2, 655–673.
2 T. Tsukuda, H. Tsunoyama and H. Sakurai, Chem.–Asian J., 2011,
6, 736–748.
3 K. Shimizu, K. Satwabe and A. Satsuma, Catal. Sci. Technol., 2011,
1, 331–341.
4 K. Shimizu, R. Sato and A. Satsuma, Angew. Chem., Int. Ed., 2009,
48, 3982–3986.
5 K. Motokura, N. Fujita, K. Mori, T. Mizugaki, K. Ebitani and K.
Kaneda, Tetrahedron Lett., 2005, 46, 5507–5510.
6 S.-I. Murahashi, T. Hirano and T. Yano, J. Am. Chem. Soc., 1978,
100, 348–350.
7 M. C. Lubinu, L. D. Luca, G. Giacomelli and A. Porcheddu, Chem.–
Eur. J., 2011, 17, 82–85.
8 A. R. McInroy, A. Uhl, T. Lear, T. M. Klapo¨tke, S. Shaikhutdinov,
S. Schauermann, G. Rupprechter, H.-J. Freund and D. Lennon1, J.
Chem. Phys., 2011, 134, 214704.
9 J. Silvestre-Albero, G. Rupprechter and H.-J. Freund, Chem. Com-
mun., 2006, 42, 80–82.
10 J. Chen, Q. Zhang, Y. Wang and H. Wan, Adv. Synth. Catal., 2008,
350, 453–464.
25 A. Dhakshinamoorthy, M. Alvaro and H. Garcia, ChemCatChem,
2010, 2, 1438–1443.
26 Z.-P. Liu and P. Hu, J. Am. Chem. Soc., 2003, 125, 1958–1967.
27 A. Y. Stakheev, Y. Zhang, A. V. Ivanov, G. N. Baeva, D. E. Ramaker
and D. C. Koningsberger, J. Phys. Chem. C, 2007, 111, 3938–3948.
28 C. H. Hu, C. Chizallet, C. Mager-Maury, M. Corral-Valero, P. Sautet,
H. Toulhoat and P. Raybaud, J. Catal., 2010, 274, 99–110.
29 K. Shimizu, Y. Miyamoto, T. Kawasaki, T. Tanji, Y. Tai and A.
Satsuma, J. Phys. Chem. C, 2009, 113, 17803–17810.
3100 | Green Chem., 2011, 13, 3096–3100
This journal is
The Royal Society of Chemistry 2011
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