Efficient heterogeneous aerobic oxidation of amines by a supported ruthenium catalyst

Article abstract of DOI:10.1002/anie.200250779

An inexpensive supported ruthenium catalyst (Ru/Al₂O₃) can be used to convert a broad range of primary (see scheme) and secondary amines into the corresponding nitriles and imines in high yields using either dioxygen or air as oxidants. The catalyst can be recycled and reused with no detectable loss of ruthenium and without an observed reduction in catalytic activity.

Full text of DOI:10.1002/anie.200250779

Angewandte
Chemie
Communications
A heterogeneous alumina-supported ruthenium catalyst, which is easy
to prepare, inexpensive to use, and capable of being recycled, has been
shown to successfully promote the oxidation of a number of primary
and secondary amines to the corresponding nitriles and imines in good
yield. For more information see the Communication by N. Mizuno and
K. Yamaguchi on the following pages.
Angew. Chem. Int. Ed. 2003, 42, 1479
DOI: 10.1002/anie.200250779
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1479

Communications
Supported Ru Catalysis of Amines
NH2
H
R
Ru/Al O3
2
+
O2
R
C
N
+
2 H2O
H2O
(1)
(2)
H
Efficient Heterogeneous Aerobic Oxidation of
Amines by a Supported Ruthenium Catalyst**
R1
R2
NHR3
R1
R2
Ru/Al2O3
NR3
+
1/2 O2
+
H
Kazuya Yamaguchi and Noritaka Mizuno*
Oxidative functional transformations of organic compounds
the best of our knowledge, the procedure reported in this
paper is an efficient and widely applicable method for the
aerobic oxidation of various amines.
[
1–3]
are important in industry and synthetic chemistry.
Stoi-
chiometric amounts of metal oxidants such as dichromate
ions, permanganate ions, manganese dioxide, silver oxide, and
lead tetraacetate are often still used for the transforma-
The catalytic activity and selectivity for the oxidation of 4-
methylbenzylamine with O (1 atm) at 373 K were compared
2
[
1–3]
tions.
The stoichiometric use and disposal of such oxidants
for a variety of ruthenium catalysts; the results are shown in
Table 1. Oxidation did not occur in the absence of the catalyst
or in the presence of g-Al O . Among the various ruthenium
is undesirable from both economical and environmental
points of view. Therefore, much attention has been paid to the
use of transition-metal catalysts to achieve effective oxida-
2
3
catalysts tested, Ru/Al O3 showed the highest catalytic
2
[
4,5]
tion, with dioxygen and hydrogen peroxide as oxidants.
Nitriles and imines are used as
activity (93% yield after 1 h) for the oxidation of 4-
versatile synthetic intermediates.
Table 1: The oxidation of 4-methylbenzylamine with dioxygen using various catalysts.[a]
Although several oxidation proce-
dures that use stoichiometric
reagents for the synthesis of nitriles
and imines from amines are
3
À1
À1
Entry
Catalyst
Rate ”10 [m min
]
Conversion of
amine [%]
Selectivity to
nitrile [%]
1
Ru/Al
O
6.25
0.16
0.07
–
2.24
0.94
–
0.98
0.72
0.19
0.09
–
>99
93
97
95
–
88
81
–
94
75
96
97
–
2
3
[
b]
[
6–9]
2
3
4
5
6
7
8
9
1
1
1
1
[(RuCl) Ca (PO ) (OH) ]
Ru(OH)
RuO2
5
2
known,
only a few catalytic pro-
2
8
4
6
2
cedures have been reported.[10–16]
3
·nH
2
O
A
no reaction
46
24
no reaction
25
22
6
number of ruthenium complexes
have been used for the oxidation
[nPr NRuO ]
4
4
RuCl
3
·nH
2
O
[
11–14]
of amines with dioxygen,
iodo-
[Ru(acac)3]
sylbenzene, and persulfate ions[16]
[15]
[RuCl (PPh ) ]
2
3 3
as oxidants. However, these systems
are not generally useful because of
their low turnover numbers and
frequencies, the formation of sig-
nificant amounts of by-products,
severe deactivation of the catalysts,
and narrow applicability to a lim-
ited number of amines.[10–16]
[RuCl
2
(DMSO)
4
]
0
1
2
3
[{RuCl (p-cymene)} ]
2
2
[RuCl (bpy) ]
3
2
2
[
c]
Al O3
no reaction
no reaction
2
no catalyst
–
–
[a] Reaction conditions: 4-Methylbenzylamine (1 mmol), Ru catalyst (Ru: 2.8 mol%), PhCF (5 mL),
3
3
73 K, O (1 atm), 1 h. Conversion and selectivity were determined by GC using diphenyl as an internal
2
standard. The main by-product was N-(4-methylbenzylidene)-4-methylbenzylamine. [b] Prepared
[11]
according to the literature procedure. [c] Al O (0.2 g).
2
3
Very recently we reported the
effective aerobic heterogeneous oxidation of both activated
and nonactivated alcohols containing sulfur, nitrogen, and
carbon–carbon double bonds with dioxygen or in air,
catalyzed by ruthenium supported on alumina (Ru/
methylbenzylamine to 4-methylbenzonitrile under the exper-
imental conditions. The reaction rate for the oxidation of 4-
methylbenzylamine was 6.25 ” 10 m min , approximately
À3
À1
40 times higher than that for the active heterogeneous catalyst
[
17]
À4
À1
Al O ).
During the course of our investigation of Ru/
[(RuCl) Ca (PO ) (OH) ]
entry 2),
(1.60 ” 10 m min ;
and higher than for homogeneous ruthenium
catalysts, such as [nPr NRuO ], RuCl , [RuCl (PPh ) ],
Table 1,
2
3
2
[
8
4
6
2
11]
Al O -catalyzed aerobic alcohol oxidation we found that this
2
3
system could be effective for the oxidation of various amines
to the corresponding nitriles or imines [Eqs. (1) and (2)]. To
4
4
3
2
3 3
[RuCl (dmso) ], [{RuCl (p-cymene)} ], and [RuCl (bpy) ]
2
4
2
2
2
2
(bpy = 2,2’-bipyridyl).
After oxidation, the Ru/Al O catalyst could be easily
2
3
[
*] Prof. Dr. N. Mizuno, Dr. K. Yamaguchi
Department of Applied Chemistry, School of Engineering
The University of Tokyo
separated by filtration; induced coupled plasma (ICP)
analysis confirmed that no Ru was present in the filtrate. In
addition, the oxidation process was terminated by the
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
removal of Ru/Al O3 from the reaction solution. These
2
Fax: (+81)3-5841-7220
E-mail: tmizuno@mail.ecc.u-tokyo.ac.jp
results indicate that any Ru species that had leached into the
reaction solution were not catalytically active and that the
[
**] This work was supported in part by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan.
[
18]
observed catalysis is truly heterogeneous. The Ru/Al O
2
3
catalyst could be reused, and both the catalytic activity and
selectivity towards oxidation reactions were retained
(entry 11 in Table 2).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
1
480
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/anie.200250779
Angew. Chem. Int. Ed. 2003, 42, 1480 – 1483

Angewandte
Chemie
[
a]
Table 2: The oxidation of various amines with dioxygen, catalyzed by Ru/Al O .
this 1:1 relationship suggests that
2
3
simple dehydrogenation does not
occur. A good linear correlation
between values of log(k /k ) and
Entry Substrate
Time [h] Conversion [%] Product
Selectivity [%]
1
2
3
4
5
6
7
8
9
benzylamine
1
1
1
1
10
2
3
15
16
>99
>99
94
>99
98
>99
84
85
benzonitrile
82
97
93
93
90
96
90
94
X
H
2-methoxybenzylamine
3-methoxybenzylamine
4-methylbenzylamine
geranylamine
2-methoxybenzonitrile
3-methoxybenzonitrile
4-methylbenzonitrile
geranylnitrile
n-octanenitrile
n-dodecanenitrile
N-benzylideneaniline
N-benzylidenebenzyla-
mine
+
[19]
the Brown–Okamoto constant s
2
(
R = 0.99; Figure 1) was observed
for the competitive oxidation of
substituted benzylamines (X = p-
Cl, p-H, p-Me, m-OMe, and p-
OMe). The resulting Hammett
parameter 1 was À0.154, which
indicates that a carbocation-type
intermediate is involved in the oxi-
n-octylamine
n-dodecylamine
N-benzylaniline
dibenzylamine
[
b]
[c]
85
84
10
11
12
indoline
indoline
1,2,3,4-tetrahydroquino-
line
2
2
7
>99
>99
95
indole
indole
quinoline
>99
>99
>99
[
d]
[
20]
dation process. When N-(4-meth-
ylbenzylidene)aniline (1 mmol) was
treated with benzylamine (2 mL)
under an argon atmosphere, N-
[a] Reaction conditions: Amine (1 mmol), Ru/Al O (Ru: 2.8 mol%), PhCF (5 mL), 373 K, O (1 atm).
2
3
3
2
Conversion and selectivity were determined by GC using naphthalene or diphenyl as an internal
standard. The main by-products were N-alkylimines. [b] p-Xylene (5 mL) was used as a solvent, and the phenyl-4-methylbenzylamine was
reaction was carried out at 403 K. [c] Benzonitrile (7% selectivity) and benzaldehyde (6% selectivity)
were formed as by-products. [d] This experiment used a recycled catalyst; the reaction conditions were
obtained together with a small
quantity of benzonitrile [Eq. (3)].
the same as those in entry 10, except that the recovered Ru/Al O catalyst was used.
2
3
The Ru/Al O3 catalyst showed high activity for the
2
oxidation of activated and non-activated amines with dioxy-
gen; the results are summarized in Table 2. All primary
benzylic amines with ÀCH NH functional groups were
2
2
converted into the corresponding benzonitriles in high
yields (Table 2; entries 1–4). The olefinic carbon–carbon
double bond did not affect oxidation under the chosen
reaction conditions, and only the amino function was dehy-
drogenated to a nitrile, without isomerization of the double
bond and intramolecular hydrogen transfer (Table 2; entry 5).
Primary aliphatic amines such as n-octylamine and n-dodecyl-
amine were effectively oxidized to the corresponding nitriles
(
Table 2; entries 6 and 7). Secondary and heterocyclic amines,
as well as primary amines, were also selectively oxidized. In
the case of the secondary amine N-benzylaniline, N-benzyli-
deneaniline was obtained in a high yield (Table 2; entry 8).
Dibenzylamine also afforded the corresponding N-benzyli-
denebenzylamine as the main product, together with benzal-
dehyde and benzonitrile (Table 2; entry 9). Heterocyclic
amines of indoline and 1,2,3,4-tetrahydroquinoline gave
indole and quinoline in greater than 99 and 95% yields,
respectively (Table 2; entries 10 and 12). The oxidation of
tertiary amines, such as pyridine and quinoline did not
proceed at all under the chosen reaction conditions.
Figure 1. Hammett plots for the oxidation of substituted benzylamines
with dioxygen using a Ru/Al O catalyst; the reaction conditions are
2
3
given in Table 2.
This fact illustrates that transfer hydrogenation from benzyl-
amine to N-(4-methylbenzylidene)aniline takes place, which
[
21–24]
suggests that a ruthenium hydride species is formed.
Small quantities of N-alkylimine products were observed
in the oxidation of primary amines, which are formed as
condensation products of the starting amines and aldehydes
through imine hydrolysis. Such findings show that imines are
formed as intermediate products which are rapidly dehydro-
genated to nitriles. The conversion and selectivity of the
oxidation of 1,2,3,4-tetrahydroquinoline was not affected by
the addition of the radical scavenger 2,6-di-tert-butyl-4-
methylphenol. In accordance with ref. [17], the skeletal
isomerization of a cyclopropyl ring does not take place. This
evidence shows that a radical is not involved in the present
oxidation reaction. The amount of dioxygen consumed was
equivalent to the quantity of 4-methylbenzylamine produced;
On the basis of the experimental results, a possible
reaction mechanism (Figure 2) is proposed. Initially, ligand
exchange between ruthenium hydroxide species and an amine
takes place to form a ruthenium amide species. The ruthe-
Angew. Chem. Int. Ed. 2003, 42, 1480 – 1483
www.angewandte.org
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1481

Communications
H
D
D
H
Ru/Al2O3 (2.8 mol%),
(4)
N
H
N
+
N
toluene, 373 K, 3 h, O2 (1 atm)
3
2.5% yield
4.0% yield
(1 mmol) was added and dioxygen was passed through the suspen-
sion. The resulting mixture was then heated at 373 K and water was
removed azeotropically under an O flow. After 1 h, 4-methylbenzo-
2
nitrile was obtained in a 93% yield (by gas chromatography). The
catalyst was separated by filtration, washed with acetone, and dried
in vacuo prior to being recycled.
Received: December 16, 2002 [Z50779]
Keywords: amines · heterogeneous catalysis · oxidation ·
.
oxygen · ruthenium
[
[
[
1] R. A. Sheldon, J. K. Kochi, Metal Catalyzed Oxidations of
Organic Compounds, Academic Press, New York, 1981.
2] C. L. Hill in Advances in Oxygenated Processes, Vol. 1 (Eds.:
A. L. Baumstark), JAI, London, 1988, p. 1.
3] M. Hudlucky, Oxidations in Organic Chemistry, American
Chemical Society, Washington, DC, 1990 (ACS Monograph
Series).
Figure 2. A possible reaction mechanism for the catalytic formation of
imines and nitriles from amines.
[
[
4] R. A. Sheldon, Green Chem. 2000, 2, G1.
5] P. T. Anastas, L. B. Bartlett, M. M. Kirchhoff, T. C. Williamson,
Catal. Today 2000, 55, 11.
[
[
[
6] P. Capdevielle, A. Lavigne, M. Maumy, Synthesis 1989, 453.
7] M. V. George, K. S. Balachandran, Chem. Rev. 1975, 75, 491.
8] J. B. Lee, C. Parkin, M. J. Shaw, N. A. Hampson, K. I. MacDon-
ald, Tetrahedron, 1973, 29, 751.
nium amide then undergoes b-hydrogen elimination to form
the corresponding imine and ruthenium hydride species, a
[
25]
process that has been discussed elsewhere.
The hydride
species was then reoxidized by dioxygen,[ and the dehydro-
genation of the imine to the nitrile rapidly takes place in the
same way as for the oxidation of primary amines with
ÀCH NH functions. Kinetic studies show a zero-order
26]
[
9] J. S. Belew, C. Garza, J. W. Mathieson, J. Chem. Soc. 1970, 634.
[10] S. Yamazaki, Y. Yamazaki, Bull. Chem. Soc. Jpn. 1990, 63, 301.
[11] K. Mori, K. Yamaguchi, T. Mizugaki, K. Ebitani, K. Kaneda,
Chem. Commun. 2001, 461.
12] A. J. Bailey, B. R. James, Chem. Commun. 1996, 2343.
13] S. Cenini, F. Porta, M. Pizzottio, J. Mol. Catal. 1982, 15, 297.
14] R. Tang, S. E. Diamond, N. Neary, F. Mares, J. Chem. Soc. Chem.
Commun. 1978, 562.
[15] F. Porta, C. Crotti, S. Cenini, J. Mol. Catal. 1989, 50, 333.
[16] G. Green, W. P. Griffith, D. M. Hollinshead, S. V. Ley, M.
Schröder, J. Chem. Soc. Perkin Trans. 1 1984, 681.
17] K. Yamaguchi, N. Mizuno, Angew. Chem. 2002, 114, 4720;
Angew. Chem. Int. Ed. 2002, 41, 4538.
18] R. A. Sheldon, M. Wallau, I. W. C. E. Arends, U. Schuchardt,
Acc. Chem. Res. 1998, 31, 485.
[19] H. C. Brown, Y. Okamoto, J. Am. Chem. Soc. 1958, 80, 4979.
[20] K. A. Connors, Chemical Kinetics, The Study of Reaction Rates
in Solution, VCH Publishers, New York, 1990.
21] R. Noyori, M. Yamakawa, S. Hashiguchi, J. Org. Chem. 2001, 66,
932.
22] E. Mizushima, M. Yamaguchi, T. Yamagishi, Chem. Lett. 1997,
37.
2
2
[
[
[
dependence for the reaction rate on both the partial pressure
of dioxygen (PO2: 0.2–2.0 atm) and the amine concentration
(
0.099–0.471m), and a first-order relationship with the amount
of Ru/Al O catalyst employed (Ru: 1.4–5.6 mol%). Further-
2
3
more, the value for the kinetic isotope effect (k /k ) was 8.1 Æ
H
D
0
.3 for the intramolecular competitive oxidation of N-phenyl-
[
a-deutero-4-methylbenzylamine at 373 K [Eq. (4)]. Based on
these facts, it is probable that b-hydrogen elimination of the
ruthenium amide species is the rate-determining step.
[
In conclusion, Ru/Al O can act as an efficient heteroge-
2
3
neous catalyst for the oxidation of non-activated, as well as
activated amines to the corresponding nitriles or imines with
[
1
atm of dioxygen or air.
7
[
2
Experimental Section
[23] R. L. Chowdhury, J.-E. Bäckvall, J. Chem. Soc. Chem. Commun.
1991, 1063.
[24] S.-I. Murahashi, T. Naota, K. Ito, Y. Maeda, H. Taki, J. Org.
Chem. 1987, 52, 4319.
The Ru/Al O catalyst (1.4 wt% Ru) was prepared by a previously
2
3
[
17]
reported method.
Solvents were carefully dried and purified
[
27]
according to a literature procedure,
and substrates were also
purified before use.[ N-Phenyl-a-deutero-4-methylbenzylamine was
synthesized by the reduction of N-(4-methylbenzylidene)aniline with
lithium aluminum deuteride, in a modification of the procedure
reported for the synthesis of deuterium-labeled toluene.[
27]
[25] S. E. Diamond, F. Mares, J. Organomet. Chem. 1977, 142, C55.
[26] While the reoxidation of ruthenium hydride species may
proceed through the formation of hydrogen peroxide, the filtrate
for the oxidation of 4-methylbenzylamine with dioxygen gave a
negative result in a peroxide test (Quantofix test stick; detection
28]
The oxidation of amines was typically carried out as follows: A
suspension of Ru/Al O (Ru: 2.8 mol%) in trifluorotoluene (5 mL)
À1
limit = 1 mgL H O ). The catalytic oxidation of 4-methylben-
2
3
2
2
was stirred for 5 min at room temperature. 4-Methylbenzylamine
zylamine with hydrogen peroxide was only moderately success-
1
482
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2003, 42, 1480 – 1483

Angewandte
Chemie
ful as a result of the rapid decomposition of hydrogen peroxide,
which is in agreement with the rapid decomposition of the
n+
Ru ÀOOH species that do not contribute to the oxidation
of the amines described in Figure 2.
[
27] Purification of Laboratory Chemicals, 3rd ed. (Eds.: D. D.
Perrin, W. L. F. Armarego), Pergamon, Oxford, UK, 1988.
28] H. L. Holland, F. M. Brown, M. Conn, J. Chem. Soc. Perkin
Trans. 2 1990, 1651.
[
Angew. Chem. Int. Ed. 2003, 42, 1480 – 1483
www.angewandte.org
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1483