Aerobic oxidative dehydrogenation of benzylamines catalyzed by a cyclometalated ruthenium complex

Article abstract of DOI:10.1016/j.tetlet.2010.10.004

The ruthenium(III) complex bearing phenylpyridine as a cyclometalated ligand serves as an efficient catalyst for the aerobic oxidative dehydrogenation of benzylamines to the corresponding benzonitriles under mild conditions.

Full text of DOI:10.1016/j.tetlet.2010.10.004

Tetrahedron Letters 51 (2010) 6457–6459
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Tetrahedron Letters
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Aerobic oxidative dehydrogenation of benzylamines catalyzed
by a cyclometalated ruthenium complex
Ayako Taketoshi a, Take-aki Koizumi b, Takaki Kanbara a,
⇑
a Tsukuba Research Center for Interdisciplinary Materials Science (TIMS), Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai,
Tsukuba 305-8573, Japan
b Chemical Resources Laboratory, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The ruthenium(III) complex bearing phenylpyridine as a cyclometalated ligand serves as an efficient
catalyst for the aerobic oxidative dehydrogenation of benzylamines to the corresponding benzonitriles
under mild conditions.
Received 26 August 2010
Revised 23 September 2010
Accepted 1 October 2010
Available online 8 October 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Dehydrogenation
Homogeneous catalysis
Ruthenium
Amine
Nitriles are useful intermediates in the synthesis of biologically
active compounds and pharmaceutical substances.1 Since nitriles
have been generally synthesized by the nucleophilic substitution
of halides with inorganic cyanides and the oxidation of amines
with a stoichiometric amount of oxidants,2 the oxidative dehydro-
genation of primary amines by molecular oxygen in air is more
desirable for the synthesis of nitriles. Therefore, the development
of efficient catalytic systems has recently been investigated for
the aerobic oxidative dehydrogenation of amines.3
transition–metal complexes.3,6,7 However, the aerobic oxidation
of primary amines to nitriles is considered to be more challenging
than that of imidazoline because it requires the removal of four
protons and four electrons. We report herein that the cyclometa-
lated complex 1a is an efficient catalyst for the aerobic oxidative
dehydrogenation of benzylamines, affording their corresponding
benzonitriles under mild conditions.
The oxidation of 4-methylbenzylamine (2a) to 4-methylbenzo-
nitrile (3a) was carried out using 1a as a catalyst in methanol under
reflux in air. The reaction was monitored by 1H NMR spectroscopy.
The desired product 3a was obtained in 90% yield after 12 h (Table
1, entry 1). The reaction proceeded much faster using molecular
oxygen (1 atm), and no catalytic reaction was observed under a
nitrogen atmosphere (entries 2 and 3). These results indicate that
molecular oxygen serves as the oxidant in the catalytic reaction.
The addition of inorganic bases accelerated the reaction; the best
result was obtained when K2CO3 was employed (entries 2 and
4–7). The addition of organic bases is less effective because they
probably co-ordinate to the ruthenium center instead of benzyl-
amine (entries 8 and 9). The reaction proceeded even at room tem-
perature; 3a was obtained in good yield (entry 10). Acetonitrile, a
solvent with a higher boiling point, was ineffective owing to its
co-ordinative property and the low solubility of K2CO3 (entry 11).
Methanol shows good solubilities for the substrate, the catalyst,
and base. The reaction could be also carried out in 1.0 mmol scale
without any problem to give 3a in good yield (entry 12).
We previously reported that
a cyclometalated ruthenium
complex, [RuCl(ppy)(tpy)][PF6] (1a)4 (ppy = 2-phenylpyridine;
tpy = 2,20:60,200-terpyridine), serves as an efficient catalyst for the
aerobic oxidative dehydrogenation of imidazoline derivatives.5
The key feature of catalyst 1a is to have a cyclometalated ligand
and a Cl ligand because the catalytic reaction is considered to pro-
ceed as follows: (i) the
r-donor character of the cyclometalated
ligand lowers the redox potential of the metal center, which en-
ables the aerobic oxidation of the ruthenium center. (ii) Since the
Cl ligand is easy to dissociate, imidazoline can co-ordinate to the
ruthenium center. The ligated imidazoline is converted to imidaz-
ole by dehydrogenation involving the removal of two protons and
two electrons. We thus envisioned that the complex 1a would be
an effective catalyst for the aerobic oxidative dehydrogenation of
primary amines, since the oxidative dehydrogenation of amines
and alcohols has been promoted by their co-ordination to
Under the optimized conditions, the aerobic dehydrogenation of
various benzylamines, 2a–g, was carried out. The corresponding
⇑
Corresponding author. Tel.: +81 29 853 5066; fax: +81 29 853 4490.
E-mail address: kanbara@ims.tsukuba.ac.jp (T. Kanbara).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.004

6458
A. Taketoshi et al. / Tetrahedron Letters 51 (2010) 6457–6459
bpy = 2,20-bipyridine), were also examined (Table 1, entries 13
Table 1
Oxidative dehydrogenation of 2a using 1a as a catalysta
and 14). As shown in entries 13 and 14, in neither case was any
3a detected. These results indicate that the redox potential of 1b
is not sufficiently low for the aerobic oxidation of the ruthenium
center (Ru(III)/Ru(II); E1/2: 1a = 0.46 V vs NHE,4 1b = 1.05 V vs
NHE9). The inactivity of 1c indicates that the reaction proceeds
only if the co-ordination of 2a to the metal center takes place.
These results are consistent with results of our previous study;5
the catalytic reaction is closely related to the aerobic oxidation of
a ligated imidazoline.10
N
N
N
PF6
Ru
N
5 mol%
NH2
Cl
CN
1a
The most commonly proposed mechanisms for ruthenium-in-
duced oxidative dehydrogenation include a b-hydrogen elimina-
tion step from the ligated amine to produce an imine.3a–d,6
However, the complex 1a is unlikely to form ruthenium hydride
species through b-hydrogen elimination because 1a and the inter-
mediates are co-ordinatively saturated. A plausible pathway of the
reaction is shown in Scheme 1. Since the Ru–Cl bond length of 1a
(2.4431(13) Å)4 is longer than that of 1b (2.3969(6) Å, see Supple-
mentary data) owing to the trans influence of the cyclometalated
ppy ligand, the dissociation of the Cl ligand followed by the co-
ordination of benzylamine proceeds. The Ru–amine complex is
converted to the Ru–imine complex by the aerobic oxidation
involving the removal of two protons and two electrons.7 The
dehydrogenation of the imine to the nitrile takes place in the same
way. Finally, benzonitrile is replaced by benzylamine. Although
further investigation of the mechanistic details is needed, it can
be considered that the base induces deprotonation of the NH group
of the co-ordinated substrate because the reaction is accelerated
under basic conditions. Molecular oxygen causes the oxidation of
the Ru center with the dehydrogenation of the co-ordinated sub-
strate and H2O is generated.
When the reaction was carried out using secondary amines, that
is, N-benzylaniline and 1,2,3,4-tetrahydroisoquinoline, under re-
flux for 24 h, N-benzylideneaniline and 3,4-dihydroisoquinoline
were obtained in 41% and 57% yields, respectively (Eq. 1). These re-
sults suggest that the reaction proceeds via the imine intermediate.
Since trace amounts of N-benzylbenzaldimines have been ob-
served in the reaction of 2a–g, which are formed by the condensa-
tion reaction of benzylamines with aldehydes through imine
hydrolysis, the ligated imine is likely to dissociate (Eq. 2).
2a
3a
CD3OD, reflux
Entry
Conditions
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
K2CO3
K2CO3
K2CO3
—
Air
O2
N2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
12
1
1
1
1
1
1
1
1
24
1
1
1
1
90
87
0
16
65
73
69
16
19
83
2
Na2CO3
Cs2CO3
KOtBu
DBU
Et3N
10c
11d
12e
13f
14f
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
80
0
0
1b
1c
a
The reaction was carried out in 1 mL solvent with 2a (0.15 mmol), 1a
(7.5 ꢀ 10ꢁ3 mmol), and base (0.15 mmol).
Determined by 1H NMR spectroscopy using mesitylene as an internal standard.
b
c
The reaction was performed at room temperature.
CD3CN was used as the solvent instead of CD3OD.
d
e
The reaction was carried out in 4 mL solvent with 2a (1.0 mmol), 1a
(5.0 ꢀ 10ꢁ2 mmol), and base (1.0 mmol).
f
Compound 1b (entry 13) and 1c (entry 14) were used as the catalyst instead of
1a.
benzonitriles, 3a–g, were obtained in each case, as shown in Table
2. When electron-withdrawing group-substituted benzylamines
were used as the substrate, the yield was low presumably owing
to the overreaction, forming by-products such as amide.8 4-Triflu-
oromethylbenzamide was detected by GC–MS and 1H NMR as one
of the by-products (10% yield) (entry 7). The reaction of aliphatic
amines 2h and i did not produce the desired nitriles under the
standard conditions (entries 8 and 9).
N
H
N
41%
Ru catalyst 1a (5 mol%), K2CO3
ð1Þ
ð2Þ
To elucidate the reaction pathway, comparable ruthenium com-
plexes, [RuCl(bpy)(tpy)][PF6] (1b) and [Ru(ppy)(bpy)2][PF6] (1c,
CD3OD, reflux, 24 h, under O2
NH
N
57%
Table 2
hydrolysis
Oxidative dehydrogenation of 2a–i using 1a as a catalysta
2
+ 2
R
R
O
NH
R
N
R
Ru catalyst 1a (5 mol%), K2CO3
R
N
R
NH2
-2H+, -2e-
Ph
CD3OD, under O2
2
3
−Cl-
Ph
Ph
H2N
Entry
R
Temp (°C)
Time (h)
Yieldb (%)
Ru
N
H
Ru
N
1a
H2
1
2
3
4
5
6
7
8
9
p-MeC6H4
m-MeC6H4
o-MeC6H4
p-MeOC6H4
Ph
p-ClC6H4
p-F3CC6H4
2-PhC2H4
3-PhC3H6
a
b
c
d
e
f
g
h
i
Reflux
Reflux
Reflux
Reflux
Reflux
30
30
Reflux
Reflux
1
1
1
1
1
24
24
1
87
75
83
86
73
61
38
0
N
Ph
-2H+, -2e-
Ph
Ru
N
Ph
1
0
H2N
a
The reaction was carried out in 1 mL solvent with 2 (0.15 mmol), 1a (7.5
ꢀ 10ꢁ3 mmol) and base (0.15 mmol).
Scheme 1. Suggested reaction pathway for the aerobic oxidative dehydrogenation
of benzylamine.
b
Determined by 1H NMR spectroscopy using mesitylene as an internal standard.

A. Taketoshi et al. / Tetrahedron Letters 51 (2010) 6457–6459
6459
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to benzonitriles under mild conditions. Since 1a provides a new
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Supplementary data
Supplementary data (general experimental information, exper-
imental detail, and X-ray data of 1b) associated with this article
can be found, in the online version, at doi:10.1016/
j.tetlet.2010.10.004.
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