Palladium nanomaterials in catalytic intramolecular C-H amination reactions

Article abstract of DOI:10.1039/c4cc03551h

Supported palladium nanomaterials catalyzed an intramolecular C-H amination reaction to produce carbazoles in moderate to excellent isolated yields, up to 92%. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc03551h

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
Palladium nanomaterials in catalytic
intramolecular C–H amination reactions†
Cite this: Chem. Commun., 2014,
50, 9049
Leng Leng Chng, Jun Yang, Yifeng Wei and Jackie Y. Ying*
Received 11th May 2014,
Accepted 9th June 2014
DOI: 10.1039/c4cc03551h
www.rsc.org/chemcomm
Supported palladium nanomaterials catalyzed an intramolecular Ag–Pd and Ag@Pd nanomaterials, and 10–12 nm for Ag2S@Pd
C–H amination reaction to produce carbazoles in moderate to nanomaterials. For the Pd nanomaterials, Pd/C, Pd/CeO2, Pd/TiO2,
excellent isolated yields, up to 92%.
Pd/Al2O3 and Pd/SiO2 (ESI,† Fig. S1d–h), the Pd nanoparticles were
synthesized in solution in the presence of the support. In these
The predominance of C–N bonds in various nitrogen-containing cases, the Pd nanoparticles have irregular morphology and a broader
natural products and therapeutically important drug molecules has size distribution of 2–5 nm for Pd/C and Pd/CeO2, 10–15 nm for
driven the development of new C–N bond forming methodologies.1 Pd/TiO2 and Pd/Al2O3, and 10–35 nm for Pd/SiO2.
Methods for C–N bond formation range from classical transforma-
The eight supported palladium nanomaterials were investigated
tions such as reductive carbonyl amination2 to newer amination for their catalytic activities in the intramolecular C–H amination
methods, including hydroamination of olefins3 and alkynes,3a,4 reaction with the model substrate 2-acetaminobiphenyl in the
allylic amination,5 alcohol amination6 and Buchwald–Hartwig presence of 4 Å molecular sieves in dimethyl sulfoxide (DMSO)
C–N bond coupling processes.7 In recent years, Pd-catalyzed C–H (Table 1, entries 1–8). With a catalyst loading of 5 mol% Pd and a
amination has emerged as an efficient synthetic method for the reaction time of 37 h at 120 1C using O2 gas as the oxidant, the Pd/C
construction of C–N bonds.8–12 These homogeneous systems have nanomaterial displayed the highest activity, giving the desired carb-
accomplished both inter-10c,d,12 as well as intramolecular8,9,10a,b,11 azole product in 92% isolated yield (Table 1, entry 4). The Pd
amination via activation of the C–H bond. The use of heterogeneous nanoparticles supported on metal oxides, i.e. Pd/CeO2, Pd/TiO2 and
catalysts such as Pd nanomaterials in these C–H amination reac- Pd/Al2O3, were also quite active and good yields of 78–86% were
tions have yet to be reported in the literature. The large surface-to-
volume ratio of the Pd nanoparticles would make them attractive as
catalysts.13 Herein, we report our results on the efficient intra-
Table 1 C–N bond formation via C–H functionalization catalyzed by Pd
nanomaterialsa
molecular C–N bond formation via C–H activation to carbazoles
catalyzed by supported Pd nanomaterials.
Eight different types of supported palladium nanomaterials were
prepared via solution methods14 (see ESI†). The size and morpho-
logy of the Pd nanoparticles depended on the preparative method as
well as the support used in the synthesis, as shown in the transmis-
sion electron microscopy (TEM) images of the Pd nanomaterials
(ESI,† Fig. S1). For the Ag–Pd, Ag@Pd and Ag2S@Pd nanomaterials
(ESI,† Fig. S1a–c), the Pd nanomaterials were first synthesized in
solution prior to their deposition onto the carbon support. Thus, the
morphology and size of these spherical nanomaterials were well
controlled. The particle diameters were in the range of 6–10 nm for
Entry
Catalyst
Pd loading (wt%)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
Ag–Pd/C
Ag@Pd/C
Ag2S@Pd/C
Pd/C
Pd/CeO2
Pd/TiO2
Pd/Al2O3
Pd/SiO2
PdCl2
4.0
4.0
4.0
5.6
5.6
5.6
5.6
5.6
—
0
0
0
92
86
78
82
53
8
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos,
Singapore 138669. E-mail: jyying@ibn.a-star.edu.sg; Fax: +65-6478-9020
† Electronic supplementary information (ESI) available: Detailed experimental
procedures; synthesis of Pd nanomaterials and catalytic experiments; TEM
images of Pd nanomaterials; characterization of products; and 1H and 13C
NMR spectra of products. See DOI: 10.1039/c4cc03551h
Pd(OAc)2
—
86
a
Reaction conditions: Pd catalyst (5 mol%), 2-acetaminobiphenyl
(0.2 mmol), 4 Å molecular sieves (0.080 g), DMSO (1.0 mL), 120 1C,
under O2, 37 h. Isolated and unoptimized yield.
b
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 9049--9052 | 9049

View Article Online
Communication
ChemComm
Table 2 C–N bond formation via C–H functionalization catalyzed by Pd/Ca
argon (Table 3, entry 2) and a low yield of 10% was attained in the
presence of air (Table 3, entry 3). Molecular sieves were also required
as they served to remove the by-product water formed during the
reaction. When the reaction was performed in the absence of
molecular sieves, there was a significant reduction in the catalytic
activity (15% isolated yield, Table 3, entry 4). A lower isolated yield
of the product (68%) was obtained when a lower catalyst loading of
2.5 mol% Pd was used (Table 3, entry 5). Comparable yields of
85–88% were achieved when either a higher (135 1C) or a lower (110 1C)
reaction temperature was applied (Table 3, entries 6 and 7). This C–H
amination reaction was also insensitive to concentration effects as
comparable yields of 88–90% were attained when either a higher
(0.4 M) or lower (0.1 M) concentration of the reaction mixture was
employed (Table 3, entries 8 and 9). The time for the C–H amination
reaction catalyzed by the Pd/C nanomaterial could be shortened to 24 h
by purging the DMSO solvent with O2 prior to the reaction (Table 3,
Entry
Solvent
Yieldb (%)
1
2
3
4
5
DMSO
DMF
DMA
1,4-Dioxane
Toluene
92
o1
o1
0
o1
a
Reaction conditions: Pd/C catalyst (5 mol%, 5.6 wt% loading of Pd),
2-acetaminobiphenyl (0.2 mmol), 4 Å molecular sieves (0.080 g), solvent
b
(1.0 mL), 120 1C, under O2, 37 h. Isolated and unoptimized yield.
attained (Table 1, entries 5–7). A moderate yield of 53% was achieved entries 10 and 11). The activity of the Pd/C catalyst was also not affected
for Pd/SiO2 (Table 1, entry 8). On the other hand, Ag–Pd/C, Ag@Pd/C by the use of less molecular sieves (0.040 g instead of 0.080 g) in the
and Ag2S@Pd/C nanomaterials were inactive for this reaction reaction. The reaction time could even be shortened to 18 h if the
(Table 1, entries 1–3). While homogeneous PdCl2 gave a low yield reaction mixture was sonicated and the headspace was re-purged with
of the product (8%, Table 1, entry 9), homogeneous Pd(OAc)2 O2 at regular intervals (Table 3, entry 12).
furnished a good yield of the desired product (86%, Table 1, entry 10).
With the optimized set of reaction conditions in hand, we
To further optimize this amination reaction, we investigated explored the scope of this C–H amination reaction catalyzed by
different conditions using the most active supported Pd/C nano- the Pd/C nanomaterial (Table 4). The substrates chosen for this
material (Tables 2 and 3). The nature of the reaction media had a study included electron-donating and electron-withdrawing groups
profound effect on the C–H amination reaction. DMSO was found on aromatic rings as well as heteroaromatic groups. This C–H
to be the best solvent (Table 2, entry 1). No product was obtained amination reaction catalyzed by the Pd/C nanomaterial was amen-
when other polar solvents (N,N-dimethylformamide (DMF), N,N- able to a wide range of substituents with different steric and
dimethylacetamide (DMA) and 1,4-dioxane) and non-polar solvent electronic properties on the ring containing the acetamide group
(toluene) were used (Table 2, entries 2–5).
(Table 4, substrates 1l–1q). Good to excellent yields of 84–92% were
Oxygen gas was crucial for this amination reaction (Table 3, entry 1) attained when either electron-donating (–CH3, Table 4, substrates
as it was required for the re-oxidation of the reduced Pd(0) species 1l–1n) or electron-withdrawing groups (–F or –CF3, Table 4, sub-
back to the active Pd(II) species (vide supra, ESI,† Scheme S1). No strates 1o–1q) were present at the ortho and/or para positions to the
product was formed when the reaction mixture was heated under acetamide moiety.
Table 3 C–N bond formation via C–H functionalization catalyzed by Pd/Ca
Entry
Pd (mol%)
Concentration (M)
Temperature (1C)
Time (h)
Atmosphere
Molecular sieves (g)
Yieldb (%)
1
2
3
4
5
6
7
8
5.0
5.0
5.0
5.0
2.5
5.0
5.0
5.0
5.0
5.0
5.0
5.0
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.4
0.1
0.2
0.2
0.2
120
120
120
120
120
110
135
120
120
120
120
120
37
37
37
37
37
37
37
37
37
24
24
18
O2
0.080
0.080
0.080
0
0.080
0.080
0.080
0.080
0.080
0.080
0.040
0.080
92
0
Argon
Air
O2
O2
O2
O2
O2
O2
O2
10
15
68
85
88
88
90
90
90
90
9
10c
11c
12d
O2
O2
a
b
Reaction conditions: Pd/C catalyst (5 mol%, 5.6 wt% loading of Pd), 2-acetaminobiphenyl (0.2 mmol), 4 Å molecular sieves, DMSO. Isolated
c
d
yield. DMSO was purged with O2 vigorously for 5 min prior to the reaction. DMSO was purged with O2 vigorously for 5 min prior to the reaction.
The reaction mixture was sonicated for 30 s, and the headspace was re-purged with O2 at regular intervals of 6 h during the reaction.
9050 | Chem. Commun., 2014, 50, 9049--9052
This journal is ©The Royal Society of Chemistry 2014

View Article Online
ChemComm
Communication
Table 4 Scope of C–N bond formation via C–H functionalization catalyzed
by Pd/Ca
atoms from the smaller clusters would detach and then reattach to
the more stable surface of the larger clusters.15 Hence, the larger
clusters would grow in size at the expense of the smaller ones. The
surface chemistry of the Pd/C catalyst before and after the amina-
tion reaction was analyzed using X-ray photoelectron spectroscopy
(XPS) (ESI,† Fig. S3). There was no significant change in the Pd 3d
XPS peaks before and after the reaction.
To determine the active catalytic species in the C–H amination, a
hot filtration test was performed. The reaction mixture was heated
at 120 1C under O2 for 4 h whereby a 37% yield of the product
(as determined by GCMS analysis) was achieved. The hot reaction
mixture was quickly filtered to remove the solids, and more
molecular sieves were added to the filtrate. The resulting mixture
was heated at 120 1C under O2 for 14 h. The reaction proceeded
further to give a final yield of 74%, indicating that the active catalyst
was probably homogeneous in nature. This was further corrobo-
rated by the high catalytic activity exhibited by homogeneous
Pd(OAc)2 (Table 1, entry 10). Similar findings were also observed
when the hot filtration tests were applied to the Pd/CeO2, Pd/TiO2
and Pd/Al2O3 nanocatalysts.
To determine the role of O2 in the amination reaction, several
hot filtration experiments were performed (ESI,† Fig. S4 and S5).
The Pd/C catalyst, the 2-acetaminobiphenyl substrate and molecular
sieves were heated at 120 1C in DMSO under O2 for 4 h, yielding
37% of the desired product by GCMS analysis (ESI,† Fig. S4). The
reaction mixture was filtered hot, followed by addition of more
Entry
Product
Ar (in 1)
Ar0 (in 1)
Yieldb (%)
1
2
3
4
5
6
7
8
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
4-CH3-(C6H4)
4-OCH3-(C6H4)
4-CF3-(C6H4)
4-F-(C6H4)
4-t-Bu-(C6H4)
6-CH3-(C6H4)
6-OCH3-(C6H4)
6-CF3-(C6H4)
6-F-(C6H4)
5-CH3-(C6H4)
—
—
—
—
—
—
—
—
—
90
78
34
83
87
68
58
46
64
79
84
85
90
90
92
90
9
—
—
10
11
12
13
14
15
16
30,50-(CH3)2-(C6H2)
30-CH3-(C6H3)
50-CH3-(C6H3)
50-F-(C6H3)
50-CF3-(C6H3)
30,50-F2-(C6H2)
—
—
—
—
—
a
Reaction conditions: Pd catalyst (5 mol%), substrate (0.2 mmol), 4 Å
molecular sieves (0.040 g), DMSO (1.0 mL, purged with O2 for 5 min),
120 1C, under O2, 24 h. b Isolated yield.
On the other hand, the C–H amination was more sensitive to the molecular sieves, and further heating at 120 1C for 14 h under either
functional groups on the aromatic ring undergoing the substitution. an O2 or argon atmosphere. In the presence of O2, the reaction
The presence of a substituent, either electron-rich (–CH3 or –OCH3, proceeded further to give a final product yield of 74%. On the other
Table 4, substrates 1g and 1h) or electron-poor (–CF3 or –F, Table 4, hand, under an argon atmosphere, the reaction did not continue
substrates 1i and 1j), at the ortho position to the biaryl axis would and the product yield remained at 37%. This set of hot filtration
result in some steric hindrance during the coupling reaction. Hence, experiments confirmed that O2 was essential for the regeneration of
lower yields of 46–68% were attained for these substrates. Good to the active catalyst required for the turnover of the catalytic reaction.
excellent yields of 78–90% were achieved when electron-donating
In another set of hot filtration experiments, the reaction mixture
(–CH3, –OCH3 or –t-Bu, Table 4, substrates 1b, 1c and 1f) or electron- was first heated at 120 1C under argon for 4 h, yielding 0% of the
withdrawing substituents (–F, Table 4, substrate 1e) were present at product (ESI,† Fig. S5). The reaction mixture was then filtered hot, and
the para position to the biaryl axis. However, with stronger electron- allowed to continue at 120 1C for 14 h in the presence of either O2 or
withdrawing groups such as –CF3 (Table 4, substrate 1d), a low yield argon. Under an argon atmosphere, no product was obtained. How-
of 34% was attained. With a –CH3 substituent at the meta position ever, in the presence of O2, 10% of the product was produced. Small
to the biaryl axis (Table 4, substrate 1k), two regioisomeric products amounts of Pd (8%) (ESI,† Table S2, entry 6) were leached into the
could be obtained. In this case, the coupling reaction was controlled DMSO solution when Pd/C was heated at 120 1C under argon for 4 h.
by steric factors, and the major carbazole product was achieved with The small amount of leached Pd was probably Pd nanoparticles as
excellent regioselectivity of 20 : 1 (GCMS analysis).
evidenced from their TEM image (ESI,† Fig. S6). Under an O2 atmo-
Heteroaromatic groups were also investigated for this C–H sphere, the leached Pd nanoparticles would react with O2 and DMSO
amination reaction (ESI,† Table S1, substrates 1r–1u). However, to produce soluble active Pd(II) species that would then react with the
these substrates could not be coupled to give the desired substrate to yield 10% of the product. These hot filtration experiments
cyclized product.
The recyclability of the Pd/C catalyst was investigated using produce the catalytically active homogeneous Pd(II) species.
2-acetaminobiphenyl, 1a, as the substrate. After one successive cycle, Inductively coupled plasma mass spectrometry (ICP-MS) analysis
proved that O2 was necessary for the leaching of Pd nanoparticles to
the catalytic activity decreased by 12% (80% isolated yield of showed that 42% of the Pd was leached into the DMSO solution
product, 2a) and after two successive cycles, the catalytic activity (probably as Pd–DMSO complexes) after heating the Pd/C catalyst at
decreased by 50% (42% isolated yield of product, 2a). TEM analysis 120 1C under O2 for 4 h (ESI,† Table S2, entry 1). DMSO is known to
of the Pd/C catalyst after the amination showed that the average act as a ligand to expedite the redox cycling between Pd(II) and Pd(0)
particle size of the Pd nanoparticles has increased to B20–30 nm in oxidation reactions.16 Likewise, for the Pd/CeO2, Pd/TiO2,
(ESI,† Fig. S2). This increase in size of the Pd nanoparticles could be Pd/Al2O3 and Pd/SiO2 catalysts, Pd species were also leached
explained by the Ostwald ripening process. During this process, the into the DMSO solution (12–25%) (ESI,† Table S2, entries 10–13).
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 9049--9052 | 9051

View Article Online
Communication
ChemComm
When DMF and DMA were used as the solvent (ESI,† Table S2, the support and the palladium species, impacting the leaching of
entries 2 and 3), ICP-MS analysis indicated that 5% of Pd was the palladium species.
leached into the solution. Insignificant Pd leaching occurred
In conclusion, we have achieved an efficient intramolecular C–N
when 1,4-dioxane and toluene were used as the solvent (ESI,† bond formation via C–H activation to carbazoles catalyzed by
Table S2, entries 4 and 5). Very minor Pd leaching was detected supported Pd nanoparticles. The C–H amination catalyzed by the
when Ag–Pd/C, Ag@Pd/C and Ag2S@Pd/C catalysts were used Pd nanoparticles most likely proceeded via a soluble Pd species.
(ESI,† Table S2, entries 7–9). These results showed a correlation
between the amount of Pd leached into the solution and the
catalytic activity of the Pd-based nanocatalyst, further confirm-
ing the homogeneous nature of the active catalyst.
Notes and references
1 (a) F. Collet, R. H. Dodd and P. Dauban, Chem. Commun., 2009,
5061; (b) M. Kienle, S. R. Dubbaka, K. Brade and P. Knochel,
Selected Pd nanocatalysts were also subjected to XPS analysis to
determine the surface oxidation state of Pd (ESI,† Fig. S7). The Pd 3d
XPS spectra of Pd/C, Pd/CeO2, Ag–Pd/C and Ag2S@Pd/C could be
deconvoluted into two pairs of doublets. The doublet with a higher
binding energy (BE) was attributed to Pd(II), while that with a lower
BE was assigned to Pd(0). The inactive Ag–Pd/C nanocomposite
material contained mainly Pd(0) surface species (B91%), while the
active Pd/C and Pd/CeO2 catalysts and the inactive Ag2S@Pd/C
nanomaterial contained more oxidized Pd(II) surface species
(B60–88%). The BEs of the Pd(II) 3d3/2 and 3d5/2 peaks for the
inactive Ag2S@Pd/C nanomaterial were shifted to lower values
(336.9 and 342.1 eV), as compared to the active Pd/C and Pd/CeO2
catalysts (337.1–337.4 eV and 342.3–342.7 eV). The presence of
mainly Pd(0) surface species on Ag–Pd/C and the different types
of Pd(II) surface species on Ag2S@Pd/C suggested different Pd
surface species and interactions with the support might account
for the dissimilar leaching behavior of these inactive nanocomposite
materials, as compared to the active Pd/C and Pd/CeO2 catalysts.
Based on these results, we propose a mechanism for the C–H
amination catalyzed by the Pd/C nanomaterial (ESI,† Scheme S1).
Soluble Pd(II) species could be leached into the solution from the
Eur. J. Org. Chem., 2007, 4166.
2 Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming,
Pergamon Press, Oxford, 1991, vol. 6.
3 (a) T. E. Mu¨ller, K. C. Hultzsch, M. Yus, F. Foubelo and M. Tada,
Chem. Rev., 2008, 108, 3795; (b) F. E. Michael and B. M. Cochran,
J. Am. Chem. Soc., 2006, 128, 4246; (c) Z. Zhang, S. D. Lee and
R. A. Widenhoefer, J. Am. Chem. Soc., 2009, 131, 5372.
4 (a) R. Severin and S. Doye, Chem. Soc. Rev., 2007, 36, 1407;
(b) F. Pohlki and S. Doye, Chem. Soc. Rev., 2003, 32, 104.
5 (a) M. Johannsen and K. A. Jorgensen, Chem. Rev., 1998, 98, 1689;
(b) G. T. Rice and M. C. White, J. Am. Chem. Soc., 2009, 131, 11707.
6 (a) T. D. Nixon, M. K. Whittlesey and J. M. J. Williams, Dalton Trans.,
´
2009, 753; (b) G. Guillena, D. J. Ramon and M. Yus, Chem. Rev., 2010,
110, 1611.
7 (a) D. S. Surry and S. L. Buchwald, Angew. Chem., Int. Ed., 2008,
47, 6338; (b) J. F. Hartwig, Acc. Chem. Res., 2008, 41, 1534; (c) D. Maiti
and S. L. Buchwald, J. Am. Chem. Soc., 2009, 131, 17423.
8 (a) W. C. P. Tsang, N. Zhang and S. Buchwald, J. Am. Chem. Soc.,
2005, 127, 14560; (b) W. C. P. Tsang, R. H. Munday, G. Brasche,
N. Zhang and S. Buchwald, J. Org. Chem., 2008, 73, 7603.
9 J. A. Jordan-Hore, C. C. C. Johansson, M. Gulias, E. M. Beck and
M. J. Gaunt, J. Am. Chem. Soc., 2008, 130, 16184.
10 (a) S. R. Fix, J. L. Brice and S. S. Stahl, Angew. Chem., Int. Ed., 2002,
41, 164; (b) M. M. Rogers, J. E. Wendlandt, I. A. Guzei and S. S. Stahl,
Org. Lett., 2006, 8, 2257; (c) V. I. Timokhin, N. R. Anastasi and
S. S. Stahl, J. Am. Chem. Soc., 2003, 125, 12996; (d) M. M. Rogers,
V. Kotov, J. Chatwichien and S. S. Stahl, Org. Lett., 2007, 9, 4331.
11 T.-S. Mei, X. Wang and J.-Q. Yu, J. Am. Chem. Soc., 2009, 131, 10806.
surface defect sites of the Pd nanoparticles. This leaching process 12 (a) Y. Obora, Y. Shimizu and Y. Ishii, Org. Lett., 2009, 11, 5058;
(b) Y. Shimizu, Y. Obora and Y. Ishii, Org. Lett., 2010, 12, 1372.
13 (a) D. Astruc, F. Lu and J. R. Aranzaes, Angew. Chem., Int. Ed., 2005,
could be facilitated by the coordinating DMSO solvent and oxidation
to Pd(II) by O2 gas. The homogeneous Pd(II) species would then form
44, 7852; (b) J. M. Campelo, D. Luna, R. Luque, J. M. Marinas and
a complex with the amide moiety of the substrate, and activate the
aromatic C–H bond. Elimination of the product would generate a
Pd(0) species which would re-oxidize to Pd(II) in the presence of
DMSO and O2. Ultimately, the dissolved Pd species would reattach
to the existing Pd nanoparticles to form larger clusters. The different
catalytic activities of the palladium nanomaterials on different
supports could be attributed to the different interactions between
A. A. Romero, ChemSusChem, 2009, 2, 18.
14 J. Yang, E. H. Sargent, S. O. Kelley and J. Y. Ying, Nat. Mater., 2009, 8, 683.
15 (a) A. Howard, C. E. J. Mitchell and R. G. Egdell, Surf. Sci., 2002,
515, L504; (b) A. Imre, D. L. Beke, E. Gontier-Moya, I. A. Szabo and
E. Gillet, Appl. Phys. A: Mater. Sci. Process., 2000, 71, 19; (c) R. Narayanan
and M. A. El-Sayed, J. Am. Chem. Soc., 2003, 125, 8340.
16 (a) B. A. Steinhoff, S. R. Fix and S. S. Stahl, J. Am. Chem. Soc., 2002,
124, 766; (b) M. S. Chen and M. C. White, J. Am. Chem. Soc., 2004,
126, 1346.
9052 | Chem. Commun., 2014, 50, 9049--9052
This journal is ©The Royal Society of Chemistry 2014