Aerobic oxidation of alcohols to aldehydes and ketones using ruthenium(III)/Et3N catalyst

Article abstract of DOI:10.1002/aoc.1848

A simple, efficient method for oxidation of primary and secondary alcohols to the corresponding aldehydes and ketones has been developed. Using RuCl ₃/Et₃N as catalyst, the oxidation of benzyl alcohol with oxygen could be achieved with 332 h^-1 turnover frequency in the absence of solvent. The influence of versatile N-containing additives on the catalytic efficiency has been discussed. The presence of minor water would substantially promote the catalytic efficiency, and its role in catalysis has been investigated in detail. The insensitive Hammett correlations of the substituted benzyl alcohols, the normal substrate isotope effect (k _H/k_D = 3.5 at 335 K), and the linear relationship between O₂ pressure and turnover frequency imply that the reoxidation of the Ru(III) hydride intermediate to the active species shares the rate-determining step with the hydride transfer in the catalytic cycle. Copyright

Full text of DOI:10.1002/aoc.1848

Full Paper
Received: 24 June 2011
Revised: 1 September 2011
Accepted: 10 September 2011
Published online in Wiley Online Library: 11 October 2011
(wileyonlinelibrary.com) DOI 10.1002/aoc.1848
Aerobic oxidation of alcohols to aldehydes and
ketones using ruthenium(III)/Et3N catalyst
Huajun Guoa, Wei-Dong Liub and Guochuan Yina*
A simple, efficient method for oxidation of primary and secondary alcohols to the corresponding aldehydes and ketones has
been developed. Using RuCl3/Et3N as catalyst, the oxidation of benzyl alcohol with oxygen could be achieved with 332 hÀ1
turnover frequency in the absence of solvent. The influence of versatile N-containing additives on the catalytic efficiency
has been discussed. The presence of minor water would substantially promote the catalytic efficiency, and its role in catalysis
has been investigated in detail. The insensitive Hammett correlations of the substituted benzyl alcohols, the normal substrate
isotope effect (kH/kD = 3.5 at 335 K), and the linear relationship between O2 pressure and turnover frequency imply that the
reoxidation of the Ru(III) hydride intermediate to the active species shares the rate-determining step with the hydride transfer
in the catalytic cycle. Copyright © 2011 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: alcohol oxidation; ruthenium(III) chloride; triethylamine; mechanism
In mechanistic studies of metal ion-mediated alcohol oxida-
Introduction
tions, [22,25–31] three key steps generally occur in the total catalytic
cycle. They are (i) formation of the metal alcoholate intermediate
by ligand exchange, (ii) hydride transfer from the C-H bond to the
metal ion to generate the Mn+-H intermediate and carbonyl prod-
uct, and finally, (iii) regeneration of the active metal species
through oxidation of the Mn+-H intermediate. The linear Ham-
mett plot of substitute effect with a negative slope generally sup-
ports that the hydride transferring to form the carbocation type
Selective oxidation of alcohols to their corresponding aldehydes
and ketones is a significant process in organic synthesis and
[1–5]
industrial manufacture.
These oxidations usually proceed
by using stoichiometric oxidants like hypochlorite, dichromate,
permanganate and chromate, which apparently cause serious
[6–10]
heavy metal pollution and toxic by-products.
Developing
clean processes for alcohol oxidations has been attracting atten-
tion for a long while in academic chemistry. For a typical alcohol
oxidation, oxygen is the greenest oxidant, and water would be
the sole byproduct if there is no further oxidation of the
corresponding carbonyl compounds occurring in the oxidation
process. However, such a green technology still remains a great
challenge.
intermediate serves as the rate-determining step in the catalytic
[11,29,32,33]
cycle.
Formation of the Mn+-H intermediate through
hydride transfer has been directly proposed in Pd, Ru, and
Au-catalyzed alcohol oxidations, and the oxygen insertion of
Pd2+-H to generate Pd2+-OOH intermediate, and then regener-
ate the active Pd2+ species with release of H2O2, has also been
[20]
proposed by Uemura.
The rate-determining step may also
A number of catalytic methods using oxygen have been exam-
[10–17]
be tunable in these three steps depending on the reaction
conditions. [34] Although much effort has been made to widely
explore versatile catalysts and to understand their mechan-
isms, the detailed roles of each composition in catalysts are
not fully understood in most cases. In this work, we report a
simple catalyst composite of simple ruthenium(III) salt with
triethylamine for alcohol oxidations. In the absence of solvent,
the oxidation could proceed with a turnover frequency of
332 hÀ1. In particular, the roles of the N-containing bases, pro-
motion of oxidation by minor water, and related mechanisms
have been widely discussed, which provides a full account of
the factors which control the oxidation in this RuCl3/Et3N system.
ined for selective oxidation of alcohols.
These methods
include using simple redox transition metal salts and their com-
plexes by homogeneous oxidation, supported transition metal
ions by heterogeneous oxidation, or transition metal free oxida-
tion using an organic catalyst like (2,2,6,6-tetramethylpiperidin-
1-yl)oxyl (TEMPO) and/or their combinations with bromide or
sodium nitrate. An early example of alcohol oxidation is Uemura’s
Pd(OAc)2/pyridine/MS3A system, in which various aromatic, alke-
nic and aliphatic alcohols could be successfully transformed to
the corresponding carbonyl compounds. [18–20] Recent promising
examples include Sheldon’s aqueous Pd/PhenS system (turnover
[21]
number 200–400),
Mizuno’s heterogeneous Ru/Al2O3 system
(turnover number close to 1000 and turnover frequency up to
[22]
340 hÀ1),
and Hu’s metal free TEMPO/HBr/NaNO2 system
*
Correspondence to: Guochuan Yin, School of Chemistry and Chemical Engi-
neering, Huazhong University of Science and Technology, Wuhan 430074,
People’s Republic of China. E-mail: gyin@hust.edu.cn
[23,24]
(turnover number up to 16 000).
However, the challenges
still remain for industrial-scale oxidation of alcohols. The substan-
tial barriers inhibiting their industrialization include use of expen-
sive ligands, toxic and corrosive co-catalysts like bromide and
NaNO2, large amounts of solvent and additives like Na2CO3,
NaOAc and molecular sieves, and low catalytic activity in most
cases (1–5% catalyst loading).
a School of Chemistry and Chemical Engineering, Huazhong University of
Science and Technology, Wuhan 430074, People’s Republic of China
b College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua
321004, People’s Republic of China
Appl. Organometal. Chem. 2011, 25, 836–842
Copyright © 2011 John Wiley & Sons, Ltd.

Aerobic oxidation of alcohols using ruthenium(III)/Et3N catalyst
reaction mixture was stirred at room temperature until the cata-
lyst was completely dissolved. Then, p-substituted benzyl alcohol
(2 mmol) was added, and the glass tube was placed in a 50 ml
stainless reactor. The reactor was charged with O2 (20 atm) and
heated at 316 K in an oil bath with stirring (1000 rpm). The pro-
ducts were analyzed by GC using ethyl benzoate as the internal
standard.
Experimental Section
Reagent Sources
The p-substituted benzyl alcohols and (Æ)-1-phenylethanol were
purchased from Alfa Aesar; benzyl-a,a-d2 alcohol (99.5 atom% D)
came from C/D/N Isotopes Inc., and other reagents came from a
local company.
General Procedure for Oxidation in the Absence of Solvent
Results and Discussion
To a 15 ml glass-lined reaction tube, RuCl3.nH2O catalyst (0.1 mmol,
0.0207 g), Et3N ligand (0.8mmol, 0.11 ml), and benzyl alcohol
(48 mmol, 5 ml) were added and stirred at room temperature until
the catalyst was completely dissolved. The reaction tube was
placed in a stainless reactor, and the resulting reactor was charged
with O2 (20 atm), heated at 371 K in an oil bath with stirring
(1000 rpm) for 20h. The conversion and selectivity were deter-
mined by gas chromatography (GC) using ethyl benzoate as the
internal standard.
Effect of Additives on Alcohol Oxidation
Using ruthenium(III) trichloride (RuCl3.nH2O) as catalyst, oxidation
of benzyl alcohol was carried out in the absence of solvent with
oxygen as the terminal oxidant. In order to investigate the mod-
ulation of the ligand on the catalytic activity of the Ru(III) cation, a
list of simple N-containing base additives were examined and the
results are summarized in Table 1. One may see that trimethyla-
mine (Me3N) and its analogue, triethylamine (Et3N), afford a sim-
ilar best efficiency for benzyl alcohol oxidation, that is, above 98%
yield of benzaldehyde (entries 3 and 4), while other N-containing
additives provide relatively lower efficiency. Imidazole provides
14% conversion with 3% yield, pyridine gives 10% conversion
with 3% yield, pyrrole affords 31% conversion with 12% yield,
and the conversion and yield are 28% and 13%, respectively,
for piperidine.
Since trimethyl and triethylamine additives demonstrate a very
similar high activity, the additional experiments were designed
under gentler reaction conditions to obtain a relatively low con-
version for distinguishing their activity difference. As shown in
Table 2, when using 0.05 mmol RuCl3.nH2O catalyst with a cata-
lyst/additive ratio of 1:8 at 371 K, triethylamine demonstrates a
better activity than trimethylamine, that is, 65% vs. 50% for con-
version, and 63% vs. 47% for selectivity. Because the commer-
cially available trimethylamine contains a large content of water
General Procedure for Versatile Alcohol Oxidation
To a 15 ml glass-lined reaction tube, RuCl3.nH2O catalyst (0.1 mmol,
0.0207 g), Et3N ligand (0.8 mmol, 0.11 ml) and t-butyl alcohol (5ml)
were added and stirred at room temperature until the catalyst was
completely dissolved. Then alcohol substrate (10 mmol) was added
and the reaction tube was placed in a stainless reactor. The result-
ing reactor was charged with O2 (20 atm), heated at 371 K in an oil
bath with stirring (1000rpm). The products were analyzed by GC or
high-performance liquid chromatography (HPLC) with the internal
standard method.
General Procedure for Oxidation through Pretreatment with
Silver Salt
To a 15 ml glass-lined reaction tube, RuCl3.nH2O catalyst (0.05 mmol,
0.0103 g), Et3N ligand (0.4 mmol, 0.056 ml), H2O (2.8 mmol, 0.05 ml),
silver salt (0.15 mmol), and benzyl alcohol (48 mmol, 5 ml) were
added and stirred at room temperature until the catalyst was com-
pletely dissolved. After removal of silver chloride through filtration,
the filtrate in the reaction tube was placed in a stainless reactor.
The resulting reactor was charged with O2 (20 atm), heated at 358 K
in an oil bath with stirring (1000 rpm). The products were analyzed
by GC using ethyl benzoate as the internal standard.
Table 1. The effect of ligand on alcohol oxidation
Entry
Ligand
pKa
Conversion (%)
Yield (%)
1
2
3
4
5
6
Pyridine
5.17
6.99
9.8
10
14
99
98
28
31
3
3
Imidazole
Me3N (33% aq)
Et3N
99
98
13
12
10.7
11.24
11.3
Piperidine
Pyrrolidine
General Procedure for the Relationship between O2 Pressure
and Turnover Frequency
Conditions: benzyl alcohol (48 mmol, 5 ml), RuCl3.nH2O (0.1 mmol,
0.0207 g), catalyst: ligand =1:8, oil bath 371 K, O2 20 atm, 20 h.
To a 15 ml glass-lined reaction tube, RuCl3.nH2O catalyst (0.1 mmol,
0.0207 g), Et3N ligand (0.8 mmol, 0.11 ml) and t-butyl alcohol (5ml)
were added and stirred at room temperature until the catalyst was
completely dissolved; then, benzyl alcohol (9.6mmol, 1 ml) was
added. The reaction tube was placed in a reactor and charged with
the required oxygen pressure, and heated at 360K in an oil bath
with stirring (1000 rpm). The products were analyzed by GC using
ethyl benzoate as the internal standard.
Table 2. Comparison of trimethylamine and triethylaminea
Entry
Ligand
Conversion (%)
Selectivity (%)
1
Me3N (aq)
Et3N
50
65
96
47
63
93
2b
3c
Et3N (aq)
aConditions: benzyl alcohol (48 mmol, 5 ml), RuCl3.nH2O (0.05 mmol,
0.0103 g), catalyst: ligand =1:8, oil bath 371 K, O2 20 atm, 14 h.
General Procedure for Kinetic Reaction for Hammett Plot
bNo additional water added.
c0.05 ml (2.8 mmol) water added (as in trimethylamine 30% aqueous
In a typical oxidation, RuCl3.nH2O catalyst (0.02 mmol, 0.0041 g),
Et3N ligand (0.16 mmol, 0.022 ml) and t-butyl alcohol (1 ml) were
added to a 15 ml glass-lined reaction tube, and the resulting
solution).
Appl. Organometal. Chem. 2011, 25, 836–842
Copyright © 2011 John Wiley & Sons, Ltd.
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H. Guo et al.
(33% aqueous solution), the extra 0.05 ml of water was added to
the reaction mixture for triethylamine to mimic the reaction con-
ditions of trimethylamine, and it generates even better results:
96% conversion with 93% selectivity. This leads to the conclusion
that triethylamine demonstrates much better activity than does
trimethylamine.
Generally, there could be at least two roles that the N-containing
[35]
base additives may play in the alcohol oxidations.
One is to
function as a ligand to modulate the redox properties of the metal
ion to facilitate alcohol oxidation; the other is to serve as a base to
assist the formation of the metal alcoholate. In the case of palla-
dium catalyst, the third role is to inhibit the formation of palladium
precipitate through coordination with the reduced palladium(0).
The pKa values of the investigated amines in the present study
are listed in Table 1, and the correlation of pKa with the catalytic
activity of the ruthenium(III) catalyst is shown in Fig. 1.
Figure 2. Influence of RuCl3/Et3N ratio on reactivity. Conditions: benzyl
alcohol (48 mmol, 5 ml), RuCl3.nH2O (0.05 mmol, 0.0103 g), catalyst:ligand
=1:8, H2O (2.8 mmol, 0.05 ml), oil bath 358 K, O2 20 atm, 4 h.
In Fig. 1 one may see that modest bases, including trimethylamine
(pKa = 9.8) and triethylamine (pKa = 10.7) provide the highest activity
in catalytic oxidation of alcohol, whereas both weak bases like
pyridine (pKa = 5.17) and strong bases like pyrrolidine (pKa =11.3)
afford lower efficiency. To examine whether the amine plays a bi-
functional role, including serving as base to assist the formation of
the metal alcoholate and coordinating with the Ru(III) ion as ligand
to modulate its redox properties, sodium bicarbonate (NaHCO3),
which is a poor ligand (pKa value = 10.33), located between trimethy-
lamine (pKa = 9.8) and triethylamine (pKa = 10.7), was added in place
of triethylamine for alcohol oxidation, and it was found that both
conversion (27%) and selectivity (74%) were much lower than those
of trimethylamine and triethylamine, suggesting that the coordina-
tion of amine with the Ru(III) ion is critical for efficient catalytic oxida-
tion. In the mass spectrum of RuCl3/Et3N in the catalytic solution,
there is only one viable mass spectral peak, at m/z =239.1 (see
Fig. S7 in supporting information), which can be related to ruthenium
cation, and it could be assignable to a [RuIII(H)(Et3N)(Cl)]+ intermedi-
ate (the existence of only one chloride anion in the sphere of the
Ru(III) ion is supported by its characteristic isotope peak). Apparently,
there is also only one triethylamine ligated to the Ru(III) cation. The
influence of the amount of triethylamine on catalytic activity is
shown in Fig. 2. Without triethylamine, using RuCl3 alone provides
only 7% conversion under the described reaction conditions. Adding
one equivalent of triethylamine could improve the yield sharply to
30%, and adding more triethylamine may further improve the cata-
lytic efficiency. For example, with the ratio of RuCl3/Et3N at 1:8, the
yield could be improved up to 52%. Taken together, the results
suggest that triethylamine may play two roles in oxidation: one
equivalent of triethylamine may be essential for coordination with
the Ru(III) cation to modulate its redox properties as demonstrated
by the mass spectrum, the remainder serving as base to help the for-
mation of the Ru(III) alcoholate.
Effect of Water on Alcohol Oxidation
As stated above, the presence of little water could surprisingly
improve the catalytic activity sharply (Table 2, entry 3). Although
alcohol oxidation has been extensively investigated in aqueous
solution or organic solvent/water solvent mixtures, [36–40] discus-
sion of the acceleration of alcohol oxidation by water and its role
in reaction is still very limited. Recently, Xu even reported a rare
water-promoted alcohol oxidation when using a VOSO4/NaNO2
catalyst system, and the role of water was interpreted to play a
key role in the redox cycle between NO and O2, and also to assist
[41]
the formation of HNO2 at the beginning.
Apparently, such
roles may not occur in the RuCl3/Et3N system reported here; thus
the alternative roles of water need to be elucidated in the present
study.
In the catalytic cycle of alcohol oxidation, the first step is the coor-
dination of alcohol to the active metal cation center through ligand
[29,34,42]
exchange to generate the metal alcoholate intermediate.
In the case of using RuCl3.nH2O as the catalyst, dissociation of chlo-
ride anion, a relatively strong donor, may accelerate the formation of
the Ru(III) alcoholate intermediate and meanwhile modulate the re-
dox properties of the Ru(III) cation to facilitate the alcohol oxidation.
Importantly, as stated earlier, the mass spectrum of the RuCl3/Et3N in
the catalytic solution revealed that only one chloride anion is at-
tached to the Ru(III) cation. Reasonably, one may expect that adding
minor water to the reaction mixture could help the dissociation of
chloride anion from the coordination sphere of the Ru(III) cation,
thus accelerating the metal alcoholate formation and improving
the catalytic efficiency. The conductivity measurements of the cata-
lytic solution provide direct evidence for the water-promoted chlo-
ride dissociation. The conductivity of pure benzyl alcohol is only
0.036 mS/cm (in the literature, it is 0.24 mS/cm with tetra-n-butylam-
monium perchlorate as supporting electrolyte). [43] The conductivity
is 0.461 mS/cm in benzyl alcohol containing 8 mM Et3N and 0.27 M
water, and 1.60 mS/cm with 1 mM RuCl3. It increases to 4.44 mS/cm
with 1 M RuCl3 and 8 M Et3N (note: Et3N reagent contains trace water
Figure 1. Correlation of pKa values of amine with catalytic efficiency.
Conditions: benzyl alcohol (48 mmol, 5 ml), RuCl3.nH2O (0.1 mmol,
0.0207 g), catalyst:ligand =1:8, oil bath 371 K, O2 20 atm, 20 h.
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Appl. Organometal. Chem. 2011, 25, 836–842

Aerobic oxidation of alcohols using ruthenium(III)/Et3N catalyst
(≤0.2%). In the case of benzyl alcohol containing 1 mM RuCl3, 8 mM
Et3N plus 0.27M water – a similar condition of catalytic oxidation –
the conductivity increases to 5.39 mS/cm. These results apparently
support the addition of minor water in promoting the dissociation
of chloride anion from RuCl3.
To further examine whether the dissociation of the chloride
anion from the Ru(III) cation is helpful for efficient catalytic
oxidation, silver salt was tested to forcefully precipitate the
chloride anion from RuCl3 in the reaction mixture prior to the
oxidation reaction. After removal of silver chloride through fil-
tration, the catalytic efficiency can be apparently improved. As
shown in Table 3, without pretreatment with silver salt it takes
10 h to achieve 76% conversion with 63% selectivity (entry 1),
whereas it can achieve 92% conversion with 99% selectivity in
10 h through pretreatment with silver salt. Apparently, removal
of chloride may improve not only the catalytic efficiency, but
also the selectivity (entry 2). Incidentally, catalytic oxidation of
alcohol by silver(I) cation itself has been eliminated through us-
ing silver(I) salt alone as catalyst (entry 3).
Figure 3. Kinetic process of alcohol oxidation with RuCl3.nH2O catalyst.
Conditions: benzyl alcohol (48 mmol, 5 ml), RuCl3.nH2O (0.05 mmol,
0.0103 g), catalyst:ligand (Et3N) = 1:8, oil bath 358 K, O2 20 atm.
Scope of RuCl3/Et3N-Mediated Alcohol Oxidation
Other evidence to suggest the acceleration of chloride disso-
ciation through adding water comes from kinetic analysis of al-
cohol oxidation (Fig. 3). Without additional water added in the
reaction mixture, an obvious induction period occurs in this
RuCl3-catalyzed alcohol oxidation. During the induction period,
water is accumulated gradually as the reaction proceeds, after
which the oxidation rate speeds up. In contrast, no induction
period was observed in the case of adding additional water to
the reaction mixture, indicating the accelerated active interme-
diate formation by adding minor water. Therefore, the com-
bined evidence strongly suggests that the role of water in the
reaction is to promote the dissociation of chloride anion from
the coordination sphere of the Ru(III) cation to facilitate metal
alcoholate formation, and thus modulate the redox properties
of the Ru(III) cation. Although oxidation can be accelerated by
adding minor water, replacing the normal water with D2O does
not reveal any solvent isotope effect, which indicates that water
is not involved in the rate-determining step of the catalytic
cycle, but may just participate in the dissociation of chloride
initially. Under the optimized conditions, The RuCl3/Et3N system
can achieve a turnover frequency of 332 hÀ1 in the absence
of solvent (equation (1)). To the best of our knowledge, this
TOF value shows one of the highest efficiencies in metal ion-
mediated alcohol oxidations.
The oxidations of versatile alcohols were investigated and the
results are summarized in Table 4. Since most substituted benzyl
alcohols are solid at room temperature, t-butanol was applied as
the solvent in this part. As shown in Table 4, benzyl alcohol can
be efficiently converted into benzyl aldehyde with or without
solvent. Under the current conditions, while the derivatives of
benzyl alcohol with electron-donating substituents could be
smoothly oxidized to the corresponding aldehydes with both
conversion and selectivity above 90%, the electron-withdrawing
substituted benzyl alcohols could also be transformed to the
corresponding aldehydes, but their selectivity is relatively low.
In the oxidation of p-nitrobenzyl alcohol, the selectivity of aldehyde
is only 42%, and o-hydroxobenzyl alcohol even provides selectivity
as low as 35%. In other cases, oxidation of 1-phenylethanol needs
35 h to achieve 100% conversion with 87% selectivity, cinnamyl alco-
hol provides 100% conversion with 88% selectivity, and allyl alcohol
gives only 72% conversion with 12% selectivity.
Interestingly, it was found that the catalytic activity of the
RuCl3/Et3N system is insensitive to the electronic effect of the
p-substituted benzyl alcohols. For example, under the identical
conditions, oxidation could be accomplished in 4 h for all of
p-CH3O-, CH3-, H-, Cl-, and CF3-substituted benzyl alcohols except
p-NO2. Such a phenomenon was further supported by the kinetic
Hammett plot for the oxidation of p-substituted benzyl alcohols.
As shown in Fig. 4 (kinetic data see also Fig. S1-S6 and Table S1
in supporting information), neither the electron-donating substit-
uents nor the electron-withdrawing substituents demonstrated
any obvious influence on the reaction rate, and the Hammett
plots of both substituent constant s and s+ provide an identical
fit, suggesting that dehydrogenation may not be any more rate
Table 3. The effect of silver sourcea
Entry
Additive
Amount (mmol)
Conversion (%)
Selectivity (%)
1
—
—
76
92
63
99
2
3b
AgSbF6
AgOAc
0.15
0.05
<1
100
aConditions: benzyl alcohol (48mmol, 5 ml), RuCl3.nH2O (0.05mmol, 0.0103 g), catalyst:ligand (Et3N)= 1:8, H2O (2.8mmol, 0.05 ml), additive, oil bath
358 K, O2 20 atm, 10 h.
bNo RuCl3.nH2O added.
Appl. Organometal. Chem. 2011, 25, 836–842
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H. Guo et al.
Table 4. Substrate scope of RuCl3/Et3N-catalyzed alcohol oxidationa
Entry
Substrate
Time (h)
Conversion(%)
Selectivity (%)
1
Benzyl alcohol
0.7
1
97
85
96
99
95
99
97
99
99
47
100
99
72
99
98
99
95
95
75
83
41
90
70
88
87
12
2b
3c
4c
5c
6c
7c
8d
9c
10c
11
12
13
Benzyl alcohol
Benzyl alcohol
4
4-Methoxybenzyl alcohol
4-Methylbenzyl alcohol
4-Chlorobenzyl alcohol
4-Trifluoromethylbenzyl alcohol
4-Nitrobenzyl alcohol
3,4-Dimethoxybenzyl alcohol
4-Hydroxybenzyl alcohol
Cinnamyl alcohol
4
4
3.5
4
12
4
4
5
1-Phenylethanol
35
4
Allyl alcohol
aConditions: alcohol (1 ml), RuCl3.nH2O (0.1 mmol, 0.0207 g), catalyst:ligand (Et3N) = 1:8, oil bath 371 K, O2 20 atm.
bAlcohol (10 mmol, 1.08 g), RuCl3.nH2O (0.025 mmol, 0.0051 g), catalyst:ligand (Et3N) = 1:8, H2O (1.4 mmol, 0.025 ml), oil bath 371 K, O2 20 atm.
cAlcohol (10 mmol), t-BuOH (5 ml).
dAlcohol (5 mmol), t-BuOH (5 ml).
limiting. These results are very rare in oxidation proceeding by a
hydride transfer process. [34,42] Generally, a linear correlation was
obtained with a negative r value, which is consistent with hydride
transfer serving as the rate-determining step. [11,29,32,33] The insen-
sitive substituent effect demonstrated here has implied that, in
this RuCl3/Et3N-catalyzed alcohol oxidation, the rate-determining
step possibly has shifted from the common hydride transfer to
other steps such as formation of the Ru(III) alcoholate or reoxida-
tion of the Ru(III) hydride intermediate.
Because the C=O group in benzaldehyde has a strong stretch-
ing frequency at ~1700 cmÀ1, it provides a chance to monitor
benzaldehyde formation by IR technology during benzyl alcohol
oxidation. It was found that, under atmospheric condition at
room temperature, formation of benzaldehyde occurs immedi-
ately but no further formation occurs after 10 min (Fig. 5). GC
analysis shows that benzyl alcohol substrate still remains domi-
nant with only trace aldehyde formation, suggesting that forma-
tion of the Ru(III) alcoholate and further hydride transfer to form
aldehyde may not be rate determining, but the reoxidation of the
Ru(III) hydride intermediate would be slow. Consequently, oxygen
pressure may have a significant influence on catalytic efficiency. As
shown in Fig. 6, turnover frequency linearly increases with the
increase in oxygen pressure, suggesting that the reoxidation of
Ru(III) hydride by oxygen most probably serves as the rate-deter-
mining step in this RuCl3/Et3N system. However, the kinetic isotope
effect provides the opposite information. The kH/kD value for
oxidation of normal benzyl alcohol and benzyl alcohol-a-a-d2 in
a single run is 3.5 at 335 K, which is very similar to the findings
for Ru/Al2O3 (kH/kD = 4.2 at 373 K), RuIV(trpy)(bpy)O2+ (kH/kD = 2.7
at 298 K), but smaller than obtained in other ruthenium catalytic
[11,29,32,44–47]
systems.
Importantly, the kH/kD value of 3.5 still sup-
ports that the hydride transfer step may be relatively slow in the
catalytic cycle, even though the Hammett plot suggests the oppo-
site conclusion. A plausible explanation is that the rates of hydride
transfer and reoxidation of the Ru(III) hydride intermediate
becomes comparable in this RuCl3/Et3N-catalyzed alcohol oxida-
tion. Increasing the oxygen pressure would accelerate the reoxida-
tion of the Ru(III) hydride intermediate, thus improving catalytic
efficiency. A plausible mechanism has been proposed for this
RuCl3/Et3N-catalyzed alcohol oxidation in which the reoxidation
of the H-Ru(III) moiety shares the rate-determining step with the
hydride transfer (Scheme 1).
Figure 4. Hammett plot for the oxidation of p-substituted benzyl
Figure 5. Time scan of the benzaldehyde formation monitored by IR
alcohols catalyzed by RuCl3/Et3N.
instrument.
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Appl. Organometal. Chem. 2011, 25, 836–842

Aerobic oxidation of alcohols using ruthenium(III)/Et3N catalyst
Conclusion
A simple RuCl3/Et3N catalytic system has been reported for oxida-
tion of primary and secondary alcohols to the corresponding
aldehydes and ketones. The N-containing additives may play
two roles in reaction: one is to serve as ligand to modulate the
redox properties of the Ru(III) cation; the other is to assist in the
formation of the metal alcoholate in the catalytic cycle. Adding
minor water to the catalytic system would substantially improve
the catalytic efficiency, and the role of water has been proposed
to accelerate the dissociation of the chloride anion from the coor-
dination sphere of the Ru(III) cation, and thus to modulate the
redox properties of the Ru(III) cation to facilitate oxidation. Under
optimal conditions, a turnover frequency of benzyl alcohol oxida-
tion of 332 hÀ1 can be achieved. The insensitive substituent effect
in the Hammett plot with a normal kH/kD value of 3.5, and the
significant influence of oxygen pressure on catalytic efficiency,
indicate that, in the catalytic cycle, the rates of hydride transfer
and reoxidation of the Ru(III) hydride intermediate are possibly
comparable, and may share the rate-determining step. The cur-
rent study not only provides a rare example in which the roles
of each catalytic composition have been clearly elucidated, but
the information obtained here may also provide an approach
for completely understanding the roles of each part in other cat-
alysts, and these advances may help in the rational design of
alcohol oxidation catalysts.
Figure 6. Relationship between O2 pressure and turnover frequency
(TOF).
SUPPORTING INFORMATION
Supporting information may be found in the online version of
this article.
Scheme 1. A plausible mechanism for the RuCl3/Et3N-mediated alcohol
oxidation.
Acknowledgments
Support by the Hubei Chutian Scholar Foundation and partially
by the National Natural Science Foundation of China (Grant
20973069) is deeply appreciated. Detection of the active interme-
diate by mass spectrometry was performed at the Analytical and
Testing Center, Huazhong University of Science and Technology.
As stated early, the only viable Ru(III) species is the (Et3N)RuIII(Cl)
having one Et3N molecule and one chloride anion ligated to the
Ru(III) cation under the reaction conditions (The net charge of
the (Et3N)RuIII(Cl) species has been ignored for convenience); thus
the (Et3N)RuIII(Cl) species has been proposed as one intermediate
in the catalytic cycle. Through ligation of the alcohol substrate to
the Ru(III) cation, the generated Ru(III) alcoholate intermediate
further proceeds hydride transfer from the C-H bond of the alco-
holate to the Ru(III) cation to generate aldehyde product with
the RuIII(H)(Et3N)(Cl) intermediate which could be oxidized by
oxygen to regenerate the active (Et3N)RuIII(Cl) species. In the
literature, there exist at least two proposed mechanisms for the
ruthenium-mediated alcohol oxidations. One is the H-Ru(III) inter-
mediate involved oxidation, in which regeneration of the active
Ru(III) species proceeds by O2 insertion of the H-Ru(III) bond
followed by HO2À release; [29,30,32,34] the other is the H-Ru(II) species
involved dehydrogenation mechanism in which the hydrogen
transfer may occur. [48–51] In our complementary experiments, the
attempts to trap the H-Ru(II) intermediate by acetone to form iso-
propanol under pressured nitrogen or oxygen failed. Since there
are no detectable Ru(II) species by mass spectrometry in the
catalytic solution and no hydrogen transfer reaction observed,
but a Ru(III) species, that is, [RuIII(H)(Et3N)(Cl)]+ at m/z = 239.1,
was detected by mass spectrometry in the catalytic solution,
the H-Ru(III) intermediate involved mechanism has been pro-
posed in this RuCl3/Et3N-mediated alcohol oxidation.
References
[1] R. A. Sheldon, J. K. Kochi, Metal-Catalyzed Oxidations of Organic Com-
pounds, Academic Press, New York, 1981.
[2] A. E. J. de Nooy, A. C. Basemer, H. van Bekkum, Synthesis 1996, 10,
1153.
[3] I. W. C. E. Arends, A. Dijksman, R. A. Sheldon, Catal. Today 2000, 57, 157.
[4] A. Baiker, T. Mallat, Catal. Today 1994, 19, 247.
[5] M. Musawir, P. N. Davey, G. Kelly, I. V. Kozhevnikov, Chem. Commun.
2003, 12, 1414.
[6] R. V. Stevens, K. T. Chapman, H. N. Weller, J. Org. Chem. 1980, 45, 2030.
[7] J. R. Holum, J. Org. Chem. 1961, 26, 4814.
[8] D. G. Lee, U. A. Spitzer, J. Org. Chem. 1970, 35, 3589.
[9] F. M. Menger, C. Lee, Tetrahedron Lett. 1981, 22, 1655.
[10] I. E. Marko, P. R. Giles, M. Tsukazaki, S. M. Brown, C. J. Urch, Science
1996, 274, 2044.
[11] A. Dijksman, A. Marino-Gonzalez, A. Mairatai Payeras, I. W. C. E.
Arends, R. A. Sheldon, J. Am. Chem. Soc. 2001, 123, 6826.
[12] G. J. ten Brink, I. W. C. E. Arends, R. A. Sheldon, Science 2000, 287, 1636.
[13] D. R. Jenson, J. S. Puqsley, M. S. Sigman, J. Am. Chem. Soc. 2001, 123, 7475.
[14] E. M. Ferreira, B. M. Stoltz, J. Am. Chem. Soc. 2001, 123, 7725.
[15] Y. Wang, J. L. DuBois, B. Hedman, K. O. Hodgson, T. D. P. Stack,
Science 1998, 279, 537.
[16] V. B. Sharma, S. L. Jain, B. Sain, Tetrahedron Lett. 2003, 44, 383.
[17] M. Kirihara, Y. Ochiai, S. Takizawa, H. Takahata, H. Nemoto, Chem.
Commun. 1999, 15, 1387.
Appl. Organometal. Chem. 2011, 25, 836–842
Copyright © 2011 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

H. Guo et al.
[18] T. Nishimura, T. Onoue, K. Ohe, S. Uemura, Tetrahedron Lett. 1998, 39,
6011.
[35] J. A. Mueller, D. R. Jensen, M. S. Sigman, J. Am. Chem. Soc. 2002, 124,
8202.
[19] T. Nishimura, T. Onoue, K. Ohe, S. Uemura, J. Am. Chem. Soc. 1999,
121, 2645.
[20] T. Nishimura, T. Onoue, K. Ohe, S. Uemura, J. Org. Chem. 1999, 64,
6750.
[36] C. B. Li, P. W. Zheng, J. Li, H. Zhang, Y. Cui, Q. Y. Shao, X. J. Ji, J. Zhang,
P. Y. Zhao, Y. L. Xu, Angew. Chem. Int. Ed. 2003, 42, 5063.
[37] G.-J. ten Brink, I. W. C. E. Arends, M. Hoogenraad, G. Verspui, R. A.
Sheldon, Adv. Synth. Catal. 2003, 245, 1341.
[21] G.-J. ten Brink, I. W. C. E. Arends, R. A. Sheldon, Adv. Synth. Catal.
2002, 344, 355.
[38] Y. Hirai, T. Kojima, Y. Mizutani, Y. Shiota, K. Yoshizawa, S. Fukuzumi,
Angew. Chem. Int. Ed. 2008, 47, 5772.
[22] K. Yamaguchi, N. Mizuno, Angew. Chem. Int. Ed. 2002, 41, 4538.
[23] R. H. Liu, X. M. Liang, C. Y. Dong, X. Q. Hu, J. Am. Chem. Soc. 2004,
126, 4112.
[39] A. Biffis, S. Cunial, P. Spontoni, L. Prati, J. Catal. 2007, 251, 1.
[40] P. Gamez, I. W. C. E. Arends, R. A. Sheldon, J. Reedijk, Adv. Synth.
Catal. 2004, 346, 805.
[24] Y. Xie, W. M. Mo, D. Xu, Z. L. Shen, N. Sun, B. X. Hu, X. Q. Hu, J. Org.
Chem. 2007, 72, 4288.
[41] Z. T. Du, H. Miao, H. Ma, Z. Q. Sun, J. P. Ma, J. Xu, Adv. Synth. Catal.
2009, 351, 558.
[25] M. Conte, H. Miyamura, S. Kobayashi, V. Chechik, J. Am. Chem. Soc.
[42] Z. Opre, J. D. Grunwaldt, T. Mallat, A. Baiker, J. Mol. Catal. A 2005, 242,
224.
2009, 131, 7189.
[26] K. M. Gligorich, M. S. Sigman, Chem. Commun. 2009, 26, 3854.
[27] R. M. Trend, B. M. Stoltz, J. Am. Chem. Soc. 2008, 130, 15957.
[28] I. W. C. E. Arends, G. Tenbrink, A. Dijksman, R. A. Sheldon, Acc. Chem.
Res. 2002, 35, 774.
[29] K. Yamaguchi, N. Mizuno, Chem. Eur. J. 2003, 9, 4353.
[30] M. M. Konnick, B. A. Gandhi, I. A. Guzei, S. S. Stahl, Angew. Chem. Int.
Ed. 2006, 45, 2904.
[31] B. Jiang, Y. Feng, E. A. Ison, J. Am. Chem. Soc. 2008, 130, 14462.
[32] K. Yamaguchi, J. W. Kim, J. L. He, N. Mizuno, J. Catal. 2009, 268, 343.
[33] A. Baiker, Z. Opre, D. Ferri, F. Krumeich, T. Mallat, J. Catal. 2006, 241,
287.
[43] Y. Nagaosa, K. Horita, S. Nishimoto, Fresenius J. Anal. Chem. 1992,
342, 698.
[44] L. Roecker, T. J. Meyer, J. Am. Chem. Soc. 1987, 109, 746.
[45] W. C. Cheng, W. Y. Yu, C. K. Li, C. M. Che, J. Org. Chem. 1998, 60, 6840.
[46] E. L. Lebeau, T. J. Meyer, Inorg. Chem. 1999, 38, 2174.
[47] M. S. Thompson, T. J. Meyer, J. Am. Chem. Soc. 1982, 104, 4106.
[48] S. I. Murahashi, T. Naota, K. Ito, Y. Maeda, H. Taki, J. Org. Chem. 1987,
52, 4319.
[49] U. Karlsson, G. Wang, J. E. Bäkvall, J. Org. Chem. 1994, 69, 1196.
[50] D. Morton, D. J. Cole-Hamilton, J. Chem. Soc. Chem. Commun. 1988,
1154.
[34] M. J. Schultz, R. S. Adler, W. Zierkiewicz, T. Privalov, M. S. Sigman,
J. Am. Chem. Soc. 2005, 127, 8499.
[51] S. Shinoda, H. Itagaki, Y. Saito, J. Chem. Soc. Chem. Commun. 1985,
860.
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