Scope, kinetics, and mechanistic aspects of aerobic oxidations catalyzed by ruthenium supported on alumina

Article abstract of DOI:10.1002/chem.200304916

The Ru/Al₂O₃ catalyst was prepared by modification of the preparation of Ru(OH)3·nH₂O. The present Ru/Al ₂O₃ catalyst has high catalytic activities for the oxidations of activated, nonactivated, and heterocyclic alcohols, diols, and amines at 1 atm of molecular oxygen. Furthermore, the catalyst could be reused seven times without a loss of catalytic activity and selectivity for the oxidation of benzyl alcohol. A catalytic reaction mechanism involving a ruthenium alcoholate species and β-hydride elimination from the alcoholate has been proposed. The reaction rate has a first-order dependence on the amount of catalyst, a fractional order on the concentration of benzyl alcohol, and a zero order on the pressure of molecular oxygen. These results and kinetic isotope effects indicate that β-elimination from the ruthenium alcoholate species is a rate-determining step.

Full text of DOI:10.1002/chem.200304916

FULL PAPER
Scope, Kinetics, and Mechanistic Aspects of Aerobic Oxidations
Catalyzed by Ruthenium Supported on Alumina
Kazuya Yamaguchi and Noritaka Mizuno*[a]
Abstract: The Ru/Al2O3 catalyst was
prepared by modification of the prepa-
ration of Ru(OH)3 ¥ nH2O. The present
Ru/Al2O3 catalyst has high catalytic
activities for the oxidations of activated,
nonactivated, and heterocyclic alcohols,
diols, and amines at 1 atm of molecular
oxygen. Furthermore, the catalyst could
be reused seven times without a loss of
catalytic activity and selectivity for the
oxidation of benzyl alcohol. A catalytic
reaction mechanism involvinga ruthe-
nium alcoholate species and b-hydride
elimination from the alcoholate has
been proposed. The reaction rate has a
first-order dependence on the amount of
catalyst, a fractional order on the con-
centration of benzyl alcohol, and a zero
order on the pressure of molecular oxy-
gen. These results and kinetic isotope
effects indicate that b-elimination from
the ruthenium alcoholate species is a
rate-determiningstep.
Keywords: alcohols
¥
amines
¥
heterogeneous catalysis ¥ molecular
oxygen ¥ supported catalysts
oxidation of 2-undecanol are low, that is, 9 and 5 hÀ1,
respectively. With the latter system, those for the oxidation
of 2-pentanol are 400 and 100 hÀ1, respectively. Even with
these systems, large quantities of co-catalysts such as NaOAc,
NaOH, and K2CO3 (0.05 2 equivalents with respect to the
alcohol) are needed to achieve high yields of carbonyl
compounds. In addition, the Pd(OAc)2/PhenS*/NaOAc sys-
tem cannot oxidize carbon carbon double bond, sulfur, or
nitrogen-containing alcohols because of strong coordination
to the Pd center.[5d,h] Therefore, little is known of widely
usable oxidations of alcohols with molecular oxygen alone.
In addition, if these oxidations could be performed with
solid (supported) catalysts, they would be environmentally
friendly because of the easy isolation of catalysts from
the products and the recycling.[9] nPr4NRuO4/MCM-41,[10a]
Introduction
Ketones and aldehydes are an important class of industrial
chemicals that have been widely used as chemical intermedi-
ates or solvents; for example, more than 8 Â 105 tons of C4
ketones and 2 Â 106 tons of C1 C3 aldehydes have been
produced in one year.[1] Alcohol oxidations are traditionally
carried out with stoichiometric metal oxidants, particularly
dichromate and permanganate, to produce enormous
amounts of heavy metal salts as wastes.[2] In this context, the
development of catalytic oxidation systems with molecular
oxygen is intrinsically ™non-waste producing∫ and of great
importance.[3]
Many methods used for the homogeneous oxidation of
alcohols catalyzed by transition metals such as ruthenium,[4]
palladium,[5] copper,[6] cobalt,[7] and vanadium[8] have recently
been reported; however, these systems have disadvantages:
large quantities of catalysts and sometimes co-catalysts such
as NaOAc, NaOH, K2CO3, N-hydroxyphthalimide (NHPI),
hydroquinone, and 2,2',6,6'-tetramethylpiperidinyloxy (TEM-
Ru/CeO2,[10b]
Ru hydrotalcite,[10c,d]
[(RuCl)2Ca8-
(PO4)6(OH)2],[10e] [RuCl2(p-cymene)]2/activated carbon,[10f]
Ru Mn Fe Cu mixed oxide,[10g,h] zeolite-confined RuO2
(RuO2-FAU),[10i] Pd or Pt on activated carbon,[11a] Pd hy-
drotalcite,[11c,d] Pd hydroxyapatite,[11e] and polymer-support-
ed Pd[11f] are examples. However, the heterogeneous oxida-
tions are limited to activated alcohols and/or the TONs and
TOFs are very low.[10, 11] Furthermore, although heterogene-
ous catalytic oxidations of alcohols with molecular oxygen
without additives in water or without solvents are environ-
mentally and technologically the most desirable methods,
efficient, widely usable catalysts are hitherto unknown.
We have very recently reported effective aerobic hetero-
geneous oxidations of alcohols and amines with molecular
oxygen or air alone catalyzed by a supported ruthenium
catalyst (Ru/Al2O3).[12] In this paper, we expand the scope and
PO) are needed, and/or kinds of substrate alcohols are
[6a,d,e]
limited. CuCl/Phen/K2CO3
and Pd(OAc)2/PhenS*/
NaOAc[5d,h] are examples of systems used for efficient aerobic
alcohol oxidations. With the former system, the turnover
number (TON) and turnover frequency (TOF) for the
[a] Prof. Dr. N. Mizuno, Dr. K. Yamaguchi
Department of Applied Chemistry, School of Engineering
The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku
Tokyo 113-8656 (Japan)
Fax : (‡81)3-5841-7220
E-mail: tmizuno@mail.ecc.u-tokyo.ac.jp
Chem. Eur. J. 2003, 9, 4353 4361
DOI: 10.1002/chem.200304916
¹ 2003 Wiley-VCH VerlagGmbH & Co. KGaA, Weinheim
4353

N. Mizuno and K. Yamaguchi
FULL PAPER
discuss the kinetic and mechanistic aspects of the aerobic
oxidations [Eqs. (1) (3)].
proceeded (entry 9). [RuCl2(PPh3)3] gave only stoichiometric
amounts of benzaldehyde (entry 11) and 18-electron ruthe-
nium complexes such as [RuCl2(dmso)4], RuCl2(bpy)2, and
[RuCl2(p-cymene)]2 were completely inactive (entries 12
14). The increase in the reaction temperature above 423 K
resulted in the successive oxidation of benzaldehyde and
decrease in the selectivity.
We used inductively coupled plasma combined with atomic
emission spectroscopy (ICP-AES) to confirm that the Ru
content of the used Ru/Al2O3 catalyst was the same as that of
the fresh catalyst and that no Ru was detected in the filtrate
(below a detection limit of 7 ppb). In addition, the oxidation
of benzyl alcohol was completely stopped by the removal of
Ru/Al2O3 from the reaction solution as shown in Figure 1.
These results indicate that any Ru species that leached into
the reaction solution is not an active homogeneous catalyst
Results and Discussion
Scope of the Ru/Al2O3-catalyzed aerobic oxidation: First, the
catalytic activity and selectivity for the oxidation of benzyl
alcohol with 1 atm of molecular oxygen as the sole oxidant
were compared with various ruthenium catalysts. The results
are shown in Table 1. No oxidation proceeded in the absence
of the catalyst or in the presence of g-Al2O3 (entries 15 and
16). Amongvarious ruthenium catalysts tested, Ru/Al 2O3 had
the highest catalytic activity and selectivity for the oxidation
of benzyl alcohol to benzaldehyde (entry 1). Neither benzoic
acid nor benzyl benzoate could be detected. When the
reactions were carried out in toluene, p-xylene, and ethyl
acetate, the reaction rates and the selectivity to benzaldehyde
were almost the same as those in trifluorotoluene. Under the
present conditions, the initial rate (R0) for the oxidation of
benzyl alcohol for Ru/Al2O3 was 1.93 Â 10À2 m minÀ1, which is
higher than that of the active homogeneous catalyst
nPr4NRuO4 (1.44 Â 10À2 m minÀ1; entry 8).[4e,f] In the case of
the catalyst precursor of RuCl3 ¥ nH2O, Friedel Crafts-type
reaction to afford o-, m-, and p-benzyltrifluorotoluenes
Figure 1. Effect of removal of Ru/Al2O3 on the oxidation of benzyl
&
alcohol. Without removal of Ru/Al2O3 ( ); an arrow indicates the removal
~
of Ru/Al2O3
(
). Reaction conditions were the same as those in Table 1.
and that the observed catalysis is truly heterogeneous in
nature.[13] The Ru/Al2O3 could be reused; when the oxidation
of benzyl alcohol was repeated even seven times, benzalde-
hyde was quantitatively produced at the same rate as that for
the first run. It is noted that air can be used instead of
molecular oxygen in the present system without changes in
conversions and selectivities for the oxidation of benzyl
alcohol.
Next, the scope of the present Ru/Al2O3 catalyst system
towards various kinds of alcohols was examined. The results
are summarized in Table 2. Ru/Al2O3 has high catalytic
activities for the oxidations of activated, nonactivated, and
heterocyclic alcohols and diols with only 1 atm of molecular
oxygen. All primary and secondary benzylic alcohols were
converted into the correspondingbenzaldehydes and ketones,
respectively, in quantitative yields (entries 1 11). The present
catalytic system was not affected by the presence of carbon
carbon double bonds in the substrates. Primary and secondary
a,b-unsaturated alcohols afforded the corresponding a,b-
unsaturated aldehydes and ketones, respectively, without
intramolecular hydrogen transfer, geometrical isomerization,
or epoxidation of the carbon carbon double bonds (en-
tries 12 14). The present system could also oxidize linear
Table 1. Oxidation of benzyl alcohol with molecular oxygen.[a]
Catalyst
Solvent
Conversion Selectivity R0 Â 102
[%]
[%]
[m minÀ1
]
1
2
3
4
5
6
7
8
Ru/Al2O3
Ru/Al2O3
Ru/Al2O3
Ru/Al2O3
PhCF3
toluene
p-xylene
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
1.93
1.88
1.84
1.99
0.77
0.03
ethyl acetate > 99
Ru/Al2O3
acetonitrile
PhCF3
PhCF3
PhCF3
PhCF3
PhCF3
PhCF3
PhCF3
PhCF3
50
2
Ru(OH)3 ¥ nH2O
RuO2 anhydrous
[nPr4NRuO4]
RuCl3 ¥ nH2O
[Ru(acac)3]
[RuCl2(PPh3)3]
[RuCl2(dmso)4]
[RuCl2(bpy)2]
no reaction
79
> 99
no reaction
5
no reaction
no reaction
no reaction
no reaction
no reaction
> 99
< 1[b]
1.44
0.08
9
10
11
12
13
14
> 99
[RuCl2(p-cymene)]2 PhCF3
15[c] Al2O3
16 none
PhCF3
PhCF3
[a] Benzyl alcohol (1 mmol), Ru catalyst (2.5 mol% Ru), PhCF3 (1.5 mL),
356 K, O2 atmosphere, 1 h. Conversion and selectivity were determined by GC
usingnaphthalene as an internal standard. [b] Friedel Crafts-type products
(o-, m-, and p-benzyltrifluorotoluenes) were formed as byproducts. [c] Al2O3
(0.2 g).
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Chem. Eur. J. 2003, 9, 4353 4361

Aerobic Oxidations
4353 4361
Table 2. Oxidation of various alcohols with molecular oxygen catalyzed by Ru/Al2O3.[a]
Substrate
t [h]
Conversion [%]
Product
Selectivity [%]
1
2
3
4
5
6
7
8
9
10
11
12
13[b]
14
benzyl alcohol
1
1
1
1
1
1
3
1
1
1.5
7
1.5
6
6
> 99
> 99
> 99
> 99
> 99
> 99
97
> 99
> 99
> 99
> 99
> 99
84
benzaldehyde
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
98
2-methylbenzyl alcohol
3-methylbenzyl alcohol
4-methylbenzyl alcohol
4-methoxybenzyl alcohol
4-chlorobenzyl alcohol
4-nitrobenzyl alcohol
1-phenylethanol
cyclopropylphenylmethanol
2,2-dimethyl-1-phenyl-1-propanol
benzhydrol
2-methylbenzaldehyde
3-methylbenzaldehyde
4-methylbenzaldehyde
4-methoxybenzaldehyde
4-chlorobenzaldehyde
4-nitrobenzaldehyde
acetophenone
cyclopropylphenylketone
2,2-dimethyl-1-phenyl-1-propanone
benzophenone
cinnamyl alcohol
3-penten-2-ol
geraniol
cinnamaldehyde
3-penten-2-one
geranial
> 99
97
89
15
16
2-pentanol
2-octanol
cyclobutanol
cyclopentanol
4-tert-butylcyclohexanol
cyclooctanol
2-adamantanol
5
2
8
8
8
6
7
2
4
4
1.5
2
1
2
2
16
2
24
90
91
85
92
90
81
> 99
> 99
87
71
> 99
93
> 99
> 99
> 99
> 99
> 99
80
2-pentanone
2-octanone
cyclobutanone
cyclopentanone
4-tert-butylcyclohexanone
cyclooctanone
2-adamantanone
camphor
n-octanal
n-decanal
2-thiophenecarboxaldehyde
3-pyridinecarboxaldehyde
4-(1-hydroxyethyl)benzaldehyde
terephthalaldehyde
phthalide
benzaldehyde
benzaldehyde
n-heptanal
> 99
> 99
99
> 99
95
> 99
> 99
99
17[b]
18[b]
19[b]
20[b]
21
22[b]
23[b,c]
24[b,c]
25
26[b]
27[d]
28[e]
29[e]
30[e]
31[e]
32[e]
(À)-borneol
1-octanol
98
99
1-decanol
2-thiophenemethanol
3-pyridinemethanol
4-(1-hydroxyethyl)benzyl alcohol
1,4-benzenedimethanol
1,2-benzenedimethanol
styrene glycol
> 99
> 99
94
> 99
98
90
hydrobenzoin
1,2-octanediol
92[f]
26
2,4-dihexyl-1,3-dioxolane
1,2-cyclooctanedione
1,8-octanedial
60[g]
59
33[e]
cis-1,2-cyclooctanediol
6
98
30
[a] Substrate (1 mmol), Ru/Al2O3 (2.5 mol% Ru), PhCF3 (1.5 mL), 356 K, O2 atmosphere. Conversion and selectivity were determined by GC or 1H NMR
usingnaphthalene or nitrobenzene as an internal standard. [b] Ru/Al 2O3 (5 mol% Ru). [c] Hydroquinone (1 equivalent with respect to Ru) was added.
[d] Substrate (0.25 mmol), Ru/Al2O3 (10 mol% Ru), DMSO (3 mL), 356 K, O2 atmosphere. [e] Substrate (0.5 mmol), Ru/Al2O3 (4 mol% Ru), toluene
(3 mL), 373 K, O2 atmosphere. [f] Selectivity [%] ˆ benzaldehyde [mol]/(2  substrate consumed [mol])  100. [g] Selectivity [%] ˆ (2  dioxolane [mol])/
substrate consumed [mol]) Â 100.
secondary and cyclic aliphatic alcohols in high yields (en-
tries 15 20). Furthermore, Ru/Al2O3 efficiently catalyzed the
oxidation of nonactivated linear aliphatic 2-octanol without
solvents. The solvent-free oxidation of 2-octanol at 423 K
(0.1 mol% Ru) had a TOF of 300 hÀ1 and the TON reached
950. The TOF and TON are the highest among those reported
for the aerobic oxidation of 2-octanol by the followingRu or
Pd catalysts: [RuCl2(PPh3)3]/TEMPO (TON and TOF, 466
and 104 hÀ1),[4i,k] Ru/quinone/Co salen (194, 97 hÀ1),[4n]
[nPr4NRuO4] (20, 6 hÀ1),[4e,f] Ru/CeO2 (30, 5 hÀ1),[10b] Ru
Co hydrotalcite (9, 5 hÀ1),[10d] [(RuCl)2Ca8(PO4)6(OH)2] (6,
1 hÀ1),[10e] Ru Mn Fe Cu mixed oxide (4, 1 hÀ1),[10g,h] zeo-
lite-confined RuO2 (RuO2-FAU) (9, 2 hÀ1 for 2-heptanol),[10i]
Pd(OAc)2/PhenS*/NaOAc (400, 10 hÀ1 for 2-hexanol),[5d] Pd
hydrotalcite (20, 2 hÀ1 for 2-dodecanol),[11c,d] Pd hydroxya-
patite (152, 6 hÀ1),[11e] and polymer-supported Pd (4, 0.2 hÀ1
for cyclooctanol).[11f]
oxidized. Extended reaction times did not improve the yields
of the aldehydes because of successive oxidation to the
correspondingcarboxylic acids. Addition of a small amount of
hydroquinone (1 equivalent with respect to Ru) completely
suppressed the successive oxidation to afford only aliphatic
aldehydes in fairly good yields (entries 23 and 24). Ru/Al2O3
successfully catalyzed the oxidation of alcohols containing
heteroatoms (oxygen, sulfur, and nitrogen) to the correspond-
ingaldehydes in hihg yields (entries 5, 25, and 26), while
monomeric complexes such as Ru and Pd could not catalyze
oxidations of these alcohols because of the strongcoordina-
tion to the metallic center.
The present procedure was further applied to the oxidation
of various kinds of diols. In the intramolecular competitive
oxidation of the primary/secondary diol 4-(1-hydroxyethyl)-
benzyl alcohol, the Ru/Al2O3 catalyst chemoselectively gave
4-(1-hydroxyethyl)benzaldehyde in 94% yield (entry 27). The
oxidation of the a,w-primary diol 1,4-benzenedimethanol
gave terephthalaldehyde (entry 28). In contrast, a quantita-
tive lactonization occurred in the case of 1,2-benzenedime-
thanol (entry 29). In the case of 1,2-diols, the product
Sterically hindered alcohols such as 2-adamantanol and
(À)-borneol were also efficiently oxidized to the correspond-
ingketones (entries 21 and 22). The less reactive aliphatic
primary alcohols 1-octanol and 1-decanol could also be
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N. Mizuno and K. Yamaguchi
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selectivities depended upon the kinds of substrates. For 1,2-
diols with phenyl rings at a-positions, only the carbon carbon
bond cleavage was observed (entries 30 and 31). For the
aliphatic linear 1,2-diol 1,2-octanediol, carbon carbon bond
cleavage to give n-heptanal occurred together with the
formation of significant amounts of 2,4-dihexyl-1,3-dioxolane
by the reaction of n-heptanal and the startingdiol (entry 32).
The oxidation of cis-1,2-cyclooctanediol afforded the corre-
sponding1,2-diketone and the carbon carbon bond cleaved
product (entry 33).
The present Ru/Al2O3 catalyst also has high catalytic
activity for the oxidation of amines with molecular oxygen.
The results are summarized in Table 3. All primary benzylic
amines tested were converted into the correspondingbenzo-
nitriles in high yields (entries 1 6). The carbon carbon
double bond did not affect the oxidation under the reaction
conditions (in a similar way to that observed for the oxidation
of alcohols) and only the amino function was dehydrogenated
to the nitrile without isomerization of the double bond or
intramolecular hydrogen transfer (entry 7). Primary aliphatic
amines such as n-octylamine and n-dodecylamine were
effectively oxidized to the correspondingnitriles (entries 8
and 9). Not only primary amines but also secondary and
heterocyclic amines were selectively oxidized. In the case of
the secondary amines N-benzylaniline and dibenzylamine, the
correspondingimines were obtained in high yields (entries 10
and 11). The heterocyclic amines indoline and 1,2,3,4-tetra-
hydroquinoline gave indole and quinoline in >99% and 95%
yields, respectively (entries 12 and 13).
cyclopropylphenyl carbinol and cyclobutanol exclusively
produced cyclopropylphenyl ketone and cyclobutanone, re-
spectively (entries 9 and 17 in Table 2). The lack of ring-
opened products indicates that free radical intermediates are
not involved in the oxidation of these substrates. When the
free radical initiator 2,2'-azobis(isobutyronitrile) (2.5 mol%)
was used instead of Ru/Al2O3, insignificant amounts of
benzaldehyde (11% yield) and benzyl benzoate (8% yield)
were produced after 48 h. Furthermore, the addition of radical
scavengers such as 2,6-di-tert-butyl-4-methylphenol, hydro-
quinone, TEMPO, and garvinoxyl (2.5 mol%) did not affect
the reaction rates or the product selectivity for oxidations of
benzyl alcohol. These results show that free radical inter-
mediates are not involved in the present alcohol oxidation and
that the abstraction of an a-hydrogen from an alcohol is not
caused by Ru/Al2O3.
The reaction rates for the oxidation of 1-octanol, 2-octanol,
benzyl alcohol, and 1-phenylethanol were 1.38 Â 10À2, 1.98 Â
10À2, 1.93 Â 10À2, and 2.81 Â 10À2 m minÀ1 at 356 K, respective-
ly, indicatingthat the oxidations of secondary alcohols
proceeded faster than primary ones. In contrast, the oxidation
of primary alcohols proceeded faster than secondary alcohols
for their mixtures (competitive oxidations). For example, an
equimolar mixture of benzyl alcohol and 1-phenylethanol
gave a mixture of benzaldehyde and acetophenone in 90%
and 24% yields, respectively, at 356 K for 1 h. The ratio of the
oxidation rate of benzyl alcohol to that of 1-phenylethanol
was 8.2. Similarly, the oxidation of 1-octanol was 12 times
faster than that of 2-octanol for the competitive oxidation. In
addition to the intermolecular competitive oxidations, the
same phenomenon was observed for the intramolecular
competitive oxidation of the primary secondary diol of
4-(1-hydroxyethyl)benzyl alcohol (entry 27 in Table 2). These
faster oxidations of primary alcohols support the formation of
ruthenium alcoholate through the ligand exchange of the
ruthenium hydroxide species with alcohols (step 1), since the
formation of metal alcoholate species is well known for the
Kinetics and mechanism: It has been reported that 2,2-
dimethyl-1-phenyl-1-propanol was oxidized to give the cor-
respondingketone with the two-electron transfer oxidant Pd II,
and that the one-electron-transfer oxidant CeIV gave benzal-
dehyde and the tert-butyl radical as primary products.[14] The
Ru/Al2O3-catalyzed oxidation of 2,2-dimethyl-1-phenyl-1-
propanol was found to yield the correspondingketone with
>99% selectivity at 100% conversion (entry 10 in Table 2).
Also, the oxidations of radical clock substrates such as
g, 10e, 15]
selective oxidation of the primary hydroxyl group.[4e
Under anaerobic conditions, the amount of acetone produced
Table 3. Oxidation of various amines with molecular oxygen catalyzed by Ru/Al2O3.[a]
Substrate
t [h]
Conversion [%]
Product
Selectivity [%]
1
2
3
4
5
6[b]
7
8
9
benzylamine
1
1
1
1
1
1
10
2
> 99
> 99
94
> 99
> 99
> 99
98
> 99
84
85
benzonitrile
82
97
93
96
93
90
90
96
90
2-methoxybenzylamine
3-methoxybenzylamine
4-methoxybenzylamine
4-methylbenzylamine
3-chlorobenzylamine
geranylamine
n-octylamine
n-dodecylamine
N-benzylaniline
dibenzylamine
2-methoxybenzonitrile
3-methoxybenzonitrile
4-methoxybenzonitrile
4-methylbenzonitrile
3-chlorobenzonitrile
geranyl nitrile
n-octanenitrile
3
n-dodecanenitrile
N-benzylideneaniline
N-benzylidenebenzylamine
indole
10
11[b]
12
15
16
2
94
85
> 99
95
84[c]
> 99
> 99
indoline
1,2,3,4-tetrahydroquinoline
13
7
quinoline
[a] Substrate (1 mmol), Ru/Al2O3 (2.8 mol% Ru), PhCF3 (5 mL), 373 K, O2 flow (1 atm). Conversion and selectivity were determined by GC using
naphthalene or diphenyl as an internal standard. The main byproducts were N-alkylimines. [b] p-Xylene (5 mL) was used as a solvent, and the reaction
temperature was 403 K. [c] Benzonitrile (7% selectivity) and benzaldehyde (6% selectivity) were formed as byproducts.
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Chem. Eur. J. 2003, 9, 4353 4361

Aerobic Oxidations
4353 4361
was approximately the same as those of Ru loaded and water
produced for the oxidation of 2-propanol. These facts also
support the proposed step 1.
Figure 2 shows the relationship between log(kX/kH) and the
‡
[16]
Brown Okamoto s
(or s) for the oxidation of benzyl
alcohols catalyzed by Ru/Al2O3. The order of reactivity for
Figure 3. Temperature dependence of intramolecular kinetic isotope
effects (kH/kD) on the reaction temperatures (333 373 K) for the oxidation
of a-deuterio-p-methylbenzyl alcohol. Reaction conditions: a-deuterio-p-
methylbenzyl alcohol (1 mmol), Ru catalyst (2.5 mol% Ru), PhCF3
(1.5 mL), 333 373 K, O2 atmosphere. Line fit: ln(kH/kD) ˆ À0.08 ‡
580.73/T (r2 ˆ 0.94).
Figure 2. Hammett plots for competitive oxidation of benzyl alcohol and
‡
While step 3 may proceed via the formation of hydrogen
peroxide, the filtrate for the oxidation of benzyl alcohol with
molecular oxygen displayed a negative peroxide test (Quan-
tofix test stick; detection limit, 1 mgLÀ1 hydrogen peroxide).
The catalytic oxidation of benzyl alcohol with hydrogen
peroxide hardly proceeded because of the rapid decomposi-
tion of hydrogen peroxide, in accordance with the rapid
decomposition of Run‡ OOH without the contribution to
oxidations of alcohols in step 4.
&
p-substituted benzyl alcohols. log(kX/kH) versus s ( ) and log(kX/kH)
~
versus s ( ). Reaction conditions: benzyl alcohol (0.5 mmol), p-substituted
benzyl alcohol (0.5 mmol), Ru/Al2O3 (1.0 mol% Ru), PhCF3 (1.5 mL),
333 K, O2 atmosphere.
benzyl alcohol was p-CH3O (kX/kH ˆ 2.27) >p-CH3 (1.55) >p-
H (1.00) >p-Cl (0.96) >p-NO2 (0.45). The slope of the linear
‡
line in Figure 2 gave a Hammett 1 value of À0.461 (r2 ˆ
‡
0.99). The moderate negative value of Hammett 1 values can
be interpreted in terms of a positively charged transition state
On the basis of all these results, we propose the mechanism
given in Scheme 1 for the Ru/Al2O3-catalyzed aerobic oxida-
tions of alcohols. This catalytic oxidation can be divided into
steps (1 4): the Run‡ alcoholate species is formed through
the ligand exchange between Run‡ hydroxide and the
alcohol (step 1). The alcoholate species undergoes typical b-
hydride elimination to afford the correspondingcarbonyl
compound and the Run‡ hydride species (step 2). The
hydride species is then reoxidized by molecular oxygen
(step 3). Reoxidation of Run‡ hydride is likely to proceed
through the insertion of molecular oxygen into Run‡ hy-
dride. The formation of water in the oxidation of 2-propanol
with molecular oxygen was monitored at various temper-
atures (333 356 K) and revealed that the amount of water
produced was the same as the amount of acetone produced
(Figure 4). The measurement of molecular oxygen uptake
duringthe oxidation of benzyl alcohol was also carried out. As
shown in Figure 5, the amount of molecular oxygen consumed
was half that of benzaldehyde produced. These respective 1:1
(H2O:product) and 1:2 (O2:product) stoichiometries indicate
that a simple dehydrogenation does not proceed and support
the overall reaction summarized in Scheme 1.
at the a-carbon atom adjacent to the phenyl ring.[17] The
‡
correlation with the Brown Okamoto s constants had
better fits than that with s constants particularly for elec-
tron-donatingsubstituents such as p-CH3O and p-CH3 (Fig-
ure 2, r2 ˆ 0.93). This fact indicates that the formation of a
carbocation transition state, which is stabilized by electron-
donatingsubstituents, is involved in the oxidation path
(step 2).[17]
When acetophenone (1m) was treated in 2-propanol under
Ar at 343 K for 12 h, almost equimolar amounts of acetone
and 1-phenylethanol were produced (93% yield), which is
consistent with the formation of the ruthenium hydride
species as an intermediate.[18] This also shows that the hydride
ion transfer from alcohol to Ru may take place (step 2).
The dependence of kH/kD values on the reaction temper-
ature was examined for Ru/Al2O3-catalyzed oxidation of a-
deuterio-p-methylbenzyl alcohol. Moderate kH/kD values
were obtained (kH/kD ˆ 4.2 5.0 at 373 333 K) and the
experimental data can be expressed by the equation ln(kH/
kD) ˆ ln(AH/AD) À DEa/RT (Figure 3). Here, the DEa value is
4.82 kJmolÀ1 and is nearly equal to the zero-point energy
H
À
À
difference for the respective C H and C D bonds (E0
À
The dependence of the rate of oxidation of benzyl alcohol
on the amount of catalyst was investigated in the range 1.25
5 mol% catalyst. As shown in Figure 6, the concentration of
benzaldehyde produced was proportional to time. Therefore,
the slope can be recognized as the rate (R0), and this was
proportional to the amount of catalyst (inset in Figure 6). This
E0 ˆ 4.90 kJmolÀ1), and AH/AD and D(DS=) are 0.92 and 0,
respectively. These values mean that the difference between
the kH and kD ratio stems only from the zero-point energies
D
(E0 À E0D), and indicates that the hydride ion transfer
H
proceeds through a symmetrical transition state in step 2.[19]
Chem. Eur. J. 2003, 9, 4353 4361
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4357

N. Mizuno and K. Yamaguchi
FULL PAPER
Figure 4. Relationship between amounts of water and acetone formed in
the oxidation of 2-propanol with molecular oxygen by Ru/Al2O3. Reaction
conditions: 2-propanol (19.6 mmol), Ru/Al2O3 (0.13 mol% Ru), 333
356 K, O2 atmosphere. Slope (water formed/acetone formed) ˆ 1.12 (r2 ˆ
0.98).
Figure 6. Effect of amount of catalyst on the oxidation of benzyl alcohol.
^
Reaction conditions: benzyl alcohol (1 mmol), Ru/Al2O3 (0.09 ( ), 0.18
~
&
*
( ), 0.27 ( ), 0.36 g( ), PhCF3 (1.5 mL), 333 K, O2 atmosphere. Inset,
reaction rate (R0) versus amount of catalyst.
indicates the first-order dependence of R0 on the amount of
catalyst. Figure 7 shows the dependence of R0 on the pressure
of molecular oxygen (PO ). The slope of lnR0 versus lnPO plots
2
2
was À0.03 (inset in Figure 7), showing that R0 was almost
Figure 5. Relationship between amounts of benzaldehyde and O2 uptake
for the oxidation of benzyl alcohol with molecular oxygen by Ru/Al2O3.
Reaction conditions: benzyl alcohol (3 mmol), Ru/Al2O3 (1.0 mol%),
PhCF3 (1.5 mL), 356 K, O2 atmosphere. Slope (O2 uptake/benzaldehyde
formed) ˆ 0.54 (r2 ˆ 0.99).
Figure 7. Reaction rate as a function of the oxygen pressure. Reaction
conditions: benzyl alcohol (1 mmol), Ru/Al2O3 (2.5 mol%) PhCF3
(1.5 mL), 356 K, PO ˆ 0.2 3.0 atm. Slope from the inset ˆ À0.03.
2
independent of PO . The zero-order dependence on the
2
pressure of molecular oxygen shows that the reoxidation
smoothly proceeds and is not a rate-determiningstep.
Ruthenium complexes have been widely studied as catalysts
for aerobic alcohol oxidations. However, the oxidation
catalysis does not often cycle because of the slow reoxidation.
The reoxidation step is usually promoted by the addition of
electron proton transfer mediators such as quinone[4d,g,n] and
TEMPO.[4i,k] It is notable that the present Ru/Al2O3 catalyst
does not need such mediators.
Figure 8a illustrates the dependence of R0 on the concen-
tration of benzyl alcohol at various temperatures. Good linear
correlations were observed between 1/R0 versus 1/[alcohol]
Scheme 1. Proposed mechanism for the Ru/Al2O3-catalyzed aerobic
oxidations of alcohols.
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Aerobic Oxidations
4353 4361
48.9 kJmolÀ1, DS2=98 K ˆ À128.1 JmolÀ1 KÀ1, and DG2=98 K
ˆ
87.1 kJmolÀ1. The activation energy (Ea) was close to that
reported for the [RuCl2(PPh3)3]/TEMPO-catalyzed aerobic
alcohol oxidation.[4i,k] From the kinetic data, the reaction rate
(R0) can be expressed as follows [Eq. (4)]:
R0 ˆÀ d[alcohol]/dt ˆ kobs[catalyst]1[alcohol]1!0
kobs ˆ 3.44  106exp(À6.18  103/T)
,
where
(4)
Kinetic isotope effects (kH/kD) at 333 K were 5.0 and 2.4 for
the intramolecular competitive oxidation of a-deuterio-p-
methylbenzyl alcohol and for the intermolecular competitive
oxidation of benzyl alcohol and [D7]benzyl alcohol
(C6D5CD2OH), respectively. Equation (4) and the kinetic
[17]
isotope effects show that step 2 is a rate-determiningstep.
Conclusion
In summary, the present Ru/Al2O3 catalyst can act as an
efficient heterogeneous catalyst for the oxidations of alcohols
and amines. The catalyst×s performance raises the prospect of
usingthis type of simple supported catalyst for oragnic
syntheses and industrial alcohol oxidation processes because
of 1) its applicability to a wide range of alcohols and amines,
2) the use of molecular oxygen or even air as an oxidant,
3) simple workup procedures (products/catalyst separation),
and 4) reusability of Ru/Al2O3. The kinetic and mechanistic
investigations show that Ru/Al2O3-catalyzed aerobic alcohol
oxidation proceeds through an alcoholate/b-hydride elimina-
tion mechanism and that the b-hydride elimination is a rate-
limitingstep.
Figure 8. a) Dependence of reaction rate on concentration of benzyl
alcohol and b) Lineweaver Burk plots. Reaction conditions: benzyl
&
alcohol (0.6 3 mmol), Ru/Al2O3 (2.5 mol%), PhCF3 (5 mL), 333 ( ), 343
~
*
(
), 356 K ( ), O2 atmosphere.
(Lineweaver Burk plots) as shown in Figure 8b. These show
that the oxidation follows Michaelis Menten-type kinetics as
a function of alcohol: first-order dependence on alcohol at the
low concentrations and zero-order dependence at higher
concentrations. The effects of reaction temperature on the
Ru/Al2O3-catalyzed oxidation of benzyl alcohol are shown in
Figure 9, and the Arrhenius plots are shown in the inset. Good
Experimental Section
Preparation of Ru/Al2O3 catalyst: The Ru/Al2O3 catalyst was prepared by a
modification of the preparation of Ru(OH)3 ¥ nH2O accordingto ref. [20].
Thus, g-Al2O3 (2.0 g, JRC-ALO-4, BET surface area: 174 m2 gÀ1) was
vigorously stirred with an aqueous solution of RuCl3 (60 mL, 8.3 Â 10À3 m)
for 15 min at room temperature. The initially brown aqueous phase became
lighter, and the powder turned dark gray. The powder was filtered, washed
with a large amount of water, and then dried in vacuo. The obtained
powder was added into deionized water (30 mL) and the pH value of the
solution was slowly adjusted to 13.2 by addition of an aqueous solution of
NaOH (1.0m), and the resultingslurry was stirred for 24 h. The powder×s
color changed from dark gray to dark green. The solid was filtered off,
washed with a large amount of water, and dried in vacuo to afford Ru/
Al2O3 (2.1 g) as a dark green powder. The contents of ruthenium and
chloride were 1.4 and 0 wt%, respectively. The BET surface area was
182 m2 gÀ1. The ESR spectrum had a signal at g ˆ 2.11, which was assigned
to Ru3‡ with a low-spin d5 electron configuration.[21] The XRD pattern was
the same as that of the g-Al2O3 support and no signals due to ruthenium
metal or dioxide were observed. Particles of ruthenium metal or dioxide
were not detected by the TEM micrograph. The IR spectrum showed a very
broad n(OH) band in the range 2900 3700 cmÀ1. These facts suggest that
ruthenium(iii) hydroxide is highly dispersed on g-Al2O3. Thus, the Ru/
Al2O3 catalyst can be easily prepared in a quantitative yield and the content
of Ru is controllable. The catalyst should be considerably less expensive
than organometallic and inorganic compounds.
Figure 9. Effect of reaction temperature on the oxidation of benzyl
alcohol. Reaction conditions: benzyl alcohol (1 mmol), Ru catalyst
~
&
^
(2.5 mol% Ru), PhCF3 (1.5 mL), 310 (Â), 320 ( ), 333 ( ), 343 ( ),
*
356 K ( ), O2 atmosphere. Inset: Arrhenius plots for the oxidation of
benzyl alcohol. R0 values were regarded as the pseudo-zero-order rate
constants (kobs) because the concentration of benzaldehyde produced was
proportional to time. Line fit: ln(kobs) ˆ 15.05 À 6180.40/T (r2 ˆ 0.99).
Typical procedures for the aerobic oxidations of alcohols: A suspension of
Ru/Al2O3 (0.18 g, 2.5 mol% Ru) in trifluorotoluene (1.5 mL) was stirred
for 5 min. Benzyl alcohol (0.11 g, 1 mmol) was added and molecular oxygen
was passed through the suspension. The resulting mixture was then heated
linearity was observed and afforded the followingactivation
parameters: Ea ˆ 51.4 kJmolÀ1, lnA ˆ 15.1, DH=
ˆ
298 K
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N. Mizuno and K. Yamaguchi
FULL PAPER
at 356 K for 1 h with azeotropic removal of water formed under an O2 flow
(ca. 1 mLminÀ1) and benzaldehyde was produced in >99% GC yield.
After the reaction, the catalyst was separated by filtration (or centrifuga-
tion) and was further washed with acetone. The filtrate was evaporated in
vacuo, and the crude product was further purified by column chromatog-
raphy on silica gel to give pure benzaldehyde (0.10 g, 95% isolated yield).
The separated Ru/Al2O3 was washed with an aqueous solution of NaOH
(1.0m) and water (30 mL), and dried in vacuo before recycling.
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Synthesis of a-deuterio-p-methylbenzyl alcohol: a-Deuterio-p-methylben-
zyl alcohol was synthesized by the reduction of p-methylbenzaldehyde
usinglithium aluminum deuteride by a modification of the procedure
reported for the synthesis of deuterium-labeled toluene.[22] Thus, a solution
of p-methylbenzaldehyde (3.2 g, 26.7 mmol) in dry THF (20 mL) was
added slowly to a suspension of lithium aluminum deuteride (0.33 g,
7.9 mmol) in dry THF (20 mL) at room temperature, and then the resulting
mixture was stirred vigorously under Ar atmosphere at 333 K. After 8 h,
the mixture was cooled to 273 K and unreacted lithium aluminum
deuteride was destroyed by the addition of water (500 mL). Then, an
aqueous solution of NaOH (50 mL, 0.1m) was added slowly to the mixture.
The resultingwhite solid was removed by filtration and washed with THF,
and the filtrate was extracted with chloroform (100 mL Â 4). The combined
extract was dried with CaCl2 and evaporated to give crude a-deuterio-p-
methylbenzyl as a white powder. The crude product was recrystallized from
petroleum ether/chloroform solution (97:3) to give the purified compound
(1.4 g, 43%) as a white sticky crystal. The product was identified by
comparison of the physical and spectral data with those of the authentic
unlabelled material. The deuterium content was estimated to be >99% by
mass spectrometry and 1H NMR spectroscopy. 1H NMR (270 MHz,
[D1]chloroform, 258C, TMS): d ˆ 7.21 (d, 3J(H,H) ˆ 7.82 Hz, 2H; aromatic
H), 7.13 (d, 3J(H,H) ˆ 7.10 Hz, 2H; aromatic H), 4.54 (s, 1H, CHDO), 2.33
(s, 3H; CH3), 2.25 ppm (d, 3J(H,H) ˆ 4.80 Hz, 1H; OH); 13C NMR
(67.5 MHz, [D1]chloroform, 258C, TMS): d ˆ 137.8, 137.2 (Cpara), 129.1
(2Cmeta), 127.1 (2Cortho), 64.7 (t, 1J(C,D) ˆ 25.7 Hz; CHDOH), 21.1 ppm
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‡
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(CH3); MS (70 eV, EI): m/z (%): 124 (19) [M ‡H], 123 (100) [M ], 121
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Acknowledgement
This work was supported in part by the Core Research for Evolutional
Science and Technology (CREST) program of the Japan Science and
Technology Corporation (JST) and a Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science, and Technology
of Japan.
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