Aerobic oxidative dehydrogenation of benzyl alcohols to benzaldehydes by using a cyclometalated ruthenium catalyst

Article abstract of DOI:10.1016/j.tetlet.2012.05.001

The ruthenium(III) complex bearing phenylpyridine as a cyclometalated ligand serves as an efficient catalyst for the aerobic oxidative dehydrogenation of benzyl alcohols to the corresponding benzaldehydes under mild conditions and for the one-pot synthesis of benzonitriles from benzyl alcohols with ammonia.

Full text of DOI:10.1016/j.tetlet.2012.05.001

Tetrahedron Letters 53 (2012) 3573–3576
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Aerobic oxidative dehydrogenation of benzyl alcohols to benzaldehydes
by using a cyclometalated ruthenium catalyst
Ayako Taketoshi a, , Xin Ning Beh a, Junpei Kuwabara 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 cat-
alyst for the aerobic oxidative dehydrogenation of benzyl alcohols to the corresponding benzaldehydes
under mild conditions and for the one-pot synthesis of benzonitriles from benzyl alcohols with ammonia.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 15 February 2012
Revised 25 April 2012
Accepted 2 May 2012
Available online 7 May 2012
Keywords:
Dehydrogenation
Homogeneous catalysis
Ruthenium
Alcohol
Aldehyde
The development of catalytic systems employing aerial oxygen
as an oxidant instead of classical toxic reagents is highly desired,1
and there are a number of reports on ruthenium-catalyzed oxida-
tive dehydrogenation.2 We previously reported a new catalytic sys-
tem in which a cyclometalated Ru(III) complex, [RuCl(ppy)(tpy)]
[PF6] (1a)3 (ppy = 2-phenylpyridine; tpy = 2,20:60,200-terpyridine),
served as an efficient catalyst for the aerobic oxidative dehydroge-
nation of imidazolines and benzylamines.4,5 The ruthenium(III)
complex bearing benzo[h]quinoline (bhq) as a cyclometalated li-
gand, [RuCl(bhq)(tpy)][PF6] (1b), was synthesized and applied as
a catalyst for aerobic oxidative dehydrogenation of benzylamines.6
The key feature of catalysts 1a and 1b is the presence of a cyclo-
alcohols. The selective oxidation of primary alcohols to aldehydes is
one of the most important reactions in organic chemistry. Although
several excellent catalysts for the aerobic oxidation of alcohols to
the corresponding carbonyl compounds have been developed,1b,c,2
primary alcohols sometimes suffer from overoxidation, thus form-
ing carboxylic acid. Therefore, selective oxidation that results in the
formation of an aldehyde is desired. We report herein that the Ru
complex 1a serves as an efficient catalyst for the aerobic oxidative
dehydrogenation of benzyl alcohols to benzaldehydes. The one-pot
synthesis of benzonitriles from benzyl alcohols with ammonia is
also described.
The oxidation of 4-methylbenzyl alcohol (2a) to 4-methylbenz-
aldehyde (3a) was carried out using 1a as a catalyst in CH2Cl2 un-
der reflux in air. The reaction was monitored by 1H NMR
spectroscopy using p-xylene as an internal standard. The desired
product 3a was obtained in 80% yield after 8 h (Table 1, entry 1).
The yield was improved when the reaction was carried out under
molecular oxygen (1 atm), whereas the same reaction under a
nitrogen atmosphere gave only 5% yield (entries 2 and 3). The re-
sults indicate that molecular oxygen serves as an oxidant in the
catalytic reaction. The yield of benzoic acid as a by-product was
negligible (entry 2). When the reaction time was extended (10 h),
the yield of 3a decreased (87%) and the yield of benzoic acid
slightly increased (3%). When CH2Cl2 and THF were used as sol-
vents, yields of 92% and 82%, respectively, were obtained (entries
2 and 8). These solvents dissolved the substrate, the catalyst, and
a part of K2CO3 during the reactions. The reaction in methanol pro-
metalated ligand and a Cl ligand. The
r-donor character of the
cyclometalated ligand lowers the redox potential of the metal cen-
ter, which enables the aerobic oxidation of the substrates. The trans
effect of the cyclometalated ligand also assists in the dissociation of
the Cl ligand followed by coordination of amines. This process pro-
vides a different catalytic reaction pathway for aerobic dehydroge-
nation from that of the common ruthenium-catalyzed aerobic
oxidation of amines, including ruthenium hydride species.2a–p
These observations persuaded us to explore coordinative substrates
other than amines. The scope of this work is the aerobic oxidation of
⇑
Corresponding author. Tel.: +81 29 853 5066; fax: +81 29 853 4490.
E-mail address: kanbara@ims.tsukuba.ac.jp (T. Kanbara).
Present address: Department of Applied Chemistry, Graduate school of Urban
Environmental Sciences, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji
192-0397, Japan.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.05.001

3574
A. Taketoshi et al. / Tetrahedron Letters 53 (2012) 3573–3576
Table 1
To elucidate the reaction pathway, the related ruthenium com-
Oxidative dehydrogenation of 2a using 1a as a catalysta
plexes, [Ru(ppy)(bpy)2][PF6] 1c and [RuCl(bpy)(tpy)][PF6] 1d, were
examined as catalysts. The control experiments revealed that nei-
ther 1c nor 1d showed catalytic activity (Table 1, entries 18 and
19). The inactivity of 1c indicates that the reaction proceeds only
if the coordination of 2a to the metal center takes place. This is con-
sistent with the fact that the use of coordinative solvents, a base,
and 2i prevents the catalytic reaction. The secondary alcohols were
less reactive than the primary alcohols as mentioned above (Table 2,
entries 14 and 15). These results also indicate that secondary alco-
hols cannot coordinate easily to the ruthenium center because of
their bulkiness. The inactivity of 1d is owing to the high redox po-
tential of the ruthenium center (Ru(III)/Ru(II); E1/2: 1a = 0.46 V vs
NHE,3 1d = 1.05 V vs NHE7); the low oxidation potential of 1a is nec-
essary for the aerobic oxidation of the ruthenium metal center. The
addition of a radical scavenger such as 2,2,6,6-tetramethylpiperi-
dine-1-oxyl radical (TEMPO) slightly affected the catalytic reac-
tions, showing that free-radical intermediates such as a benzyl
radical were not involved in this reaction.2f Since these results are
consistent with the results of our previous reports on the oxidation
of amines,4,5 the catalytic reaction of 1a is closely related to the aer-
obic oxidation of amines. A plausible reaction pathway for the reac-
tion is shown in Scheme 1: the dissociation of the Cl ligand occurs
easily owing to the trans effect of the cyclometalated ppy ligand.
The coordination of benzyl alcohol to the metal center affords the
Ru-alcohol complex. The Ru-alcohol complex is then converted into
the Ru-aldehyde complex by aerobic oxidation involving the re-
moval of two protons and two electrons; the reaction is likely to re-
sult from the disproportionation of the ruthenium intermediate to
form a Ru(IV) species containing dissociable protons.4,8 Finally,
the aldehyde is replaced by alcohol. The base induces deprotona-
tion of the coordinated OH group because the reaction proceeded
smoothly by using more than 1 equiv molar amount of the base.
Mayer et al. reported related ruthenium-promoted dehydrogena-
tion of ligated substrates,9 which was elucidated by a metal-
mediated hydrogen atom transfer reaction. We consider that
Mayer’s and our pathways have little difference, if the resonance
structures are taken into consideration (Scheme S1 and S2).
Because 1a was an efficient catalyst for the aerobic oxidative
dehydrogenation of benzyl alcohols to benzaldehydes, we applied
1a as a catalyst for the one-pot synthesis of benzonitrile from ben-
zyl alcohol with ammonia. There are only a few reports of the syn-
thesis of benzonitriles directly from benzyl alcohols using aerobic
oxidations.10 This transformation is considered to proceed via the
following three sequential reactions: (1) the oxidation of alcohol,
(2) the condensation of aldehyde and ammonia, and (3) the oxida-
tion of imine. We initially expected that the one-pot synthesis
could be achieved by 1a because 1a was effective for the aerobic
oxidation of amines as well as alcohols. However, when the oxida-
tion of alcohol was carried out in the presence of ammonia, the de-
sired product benzonitrile 4a was obtained in low yield (24 h, 18%).
The highly coordinative ability of ammonia and 4a prevented the
aerobic oxidation of 2a. However, 4a was obtained in high yield
(87%) when the ammonia solution was added to the reaction mix-
ture after the conversion of alcohol 2a to aldehyde 3a (Scheme 2).
A similar reaction of diol 2m gave 4-(3-hydroxypropoxy)benzoni-
trile (4m) in 64% yield, which was realized by using the difference
in reactivity of the hydroxy groups. Because 4m is known to be an
intermediate for the synthesis of biologically active compounds
and liquid crystal materials,11 this reaction would be a promising
method for the preparation of industrially important chemical
products.
N
N
N
PF6
Ru
N
5 mol%
Cl
1a
OH
O
2a
3a
Yieldb (%)
Reflux Air 80
Reflux O2
Reflux N2
Entry
Conditions
CH2Cl2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18c
19c
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
—
CH2Cl2
CH2Cl2
CHCl3
92
5
60
60
O2
O2
O2
O2
O2
O2
O2
O2
46
21
27
10
82
64
9
CHCl2CHCl2
1,2-Dichlorobenzene 60
DME
THF
60
60
60
60
60
CH3OH
Acetone
CH3CN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
6
0
Reflux O2
Reflux O2
Reflux O2
Reflux O2
Reflux O2
Reflux O2
Reflux O2
Reflux O2
Na2CO3
Cs2CO3
DBU
25
18
2
82
91
0
K2CO3 (0.5 equiv) CH2Cl2
K2CO3 (2.0 equiv) CH2Cl2
K2CO3
K2CO3
CH2Cl2
CH2Cl2
0
Reaction conditions: 2a (0.15 mmol), 1a (7.5 ꢀ 10ꢁ3 mmol), base (0.15 mmol),
a
solvent (1.0 mL), 8 h.
Determined by 1H NMR spectroscopy using p-xylene as an internal standard.
Complex 1c (entry 18) and 1d (entry 19) were used as a catalyst instead of 1a.
b
c
ceeded slowly because the substrate competed with the solvent
(entry 9). Acetone and CH3CN were ineffective solvents probably
because of their coordinative ability to the metal center and the
low solubility of K2CO3 (entries 10 and 11). The addition of inor-
ganic bases accelerated the reaction (entries 2, 12–14); the best re-
sult was obtained when K2CO3 was used. The addition of organic
bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was less
effective probably because they coordinate to the ruthenium cen-
ter instead of the substrate (entry 15). The reaction with 2 equiv
molar amounts of K2CO3 provided the better yield (91%) than that
with 0.5 equiv molar amounts of K2CO3 (82%) (entries 2, 16, and
17).
The aerobic oxidative dehydrogenation of various alcohols, 2b–
2o, was carried out under the optimized conditions (Table 1, entry
2). The substitution of phenyl groups with either electron-donating
group or electron-withdrawing group was tolerated to afford the
desired products (Table 2, entries 1–7). The reactions of furfuryl
alcohol 2h and allylic alcohol 2j also gave the corresponding alde-
hydes in good yields (entries 8 and 10). In contrast, the reaction of
3-pyridinemethanol 2i did not give the desired product (entry 9).
The low yield of the product is attributed to the coordination of
the pyridine moiety of 2i to the ruthenium center. The progress
of the reaction of the aliphatic alcohols without resonance stabil-
ization was negligible (entries 11 and 12). The oxidation of 4-(3-
hydroxypropoxy)benzyl alcohol (2m) gave 4-(3-hydroxyprop-
oxy)benzaldehyde (3m) in good yield, indicating that the benzylic
hydroxy group of 2m was selectively oxidized. Although the corre-
sponding ketones were obtained from the reactions of secondary
alcohols 2n and 2o (entries 14 and 15), the secondary alcohols
were less reactive than the primary alcohols.
In summary, the cyclometalated ruthenium complex 1a effec-
tively catalyzed the oxidative dehydrogenation of benzyl alcohols
to benzaldehydes under mild conditions. The scope of the aerobic
oxidation was expanded to the one-pot synthesis of benzonitrile

A. Taketoshi et al. / Tetrahedron Letters 53 (2012) 3573–3576
3575
Table 2
Oxidative dehydrogenation of 2a–2o using 1a as a catalysta
Entry
1
Substrate
Product
Yieldb (%)
OH
OH
O
2a
2b
3a
3b
92
93
O
2
OH
OH
O
O
3
4
2c
3c
70
90
2d
3d
O
OH
5
6
2e
2f
3e
3f
82
84
H3CO
F3C
H3CO
F3C
O
OH
OH
O
7
2g
2h
2i
3g
3h
3i
86
81
2
O2N
O
O2N
O
OH
OH
O
8
O
9
N
N
O
OH
OH
10
2j
3j
89
O
11c
12c
2k
2l
3k
3l
7
3
OH
O
OH
O
13
2m
2n
2o
3m
3n
3o
82
21
10
HO
O
HO
O
14c
15c
OH
OH
O
O
a
b
c
Reaction conditions: 2 (0.15 mmol), 1a (7.5 ꢀ 10ꢁ3 mmol), K2CO3 (0.15 mmol), CH2Cl2 (1.0 mL), reflux, 8 h, O2 atmosphere.
Determined by 1H NMR spectroscopy using p-xylene as an internal standard.
Reaction time: 24 h.
O2
5 mol% Ru catalyst 1a, K2CO3
OH
O
CH2Cl2, reflux, 10 h, under O2
Ph
2a
3a
1a
RuII
O
HO
Ph
Ph
disproportionation
RuIII
Ph
2 M NH3 in CH3OH
70 °C, 6 h
CN
+
O
NH
H
-H+
Ph
Cl-
4a
87%
RuIV
O
RuIII
O
H
-H+
OH
5 mol% Ru catalyst 1a, K2CO3
Ph
HO
O
CH2Cl2, reflux, 12 h, under O2
RuII
O
2m
CN
O2
2 M NH3 in CH3OH
70 °C, 6 h
HO
O
HO
Ph
4m
64%
Ph
O
Scheme 1. Suggested reaction pathway for the aerobic oxidative dehydrogenation
of benzyl alcohol.
Scheme 2. One-pot synthesis of benzonitrile 4a and 4m.

3576
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Acknowledgments
This research was supported by the Sasagawa Scientific Re-
search Grant from The Japan Science Society and the Cooperative
Research Program of the ‘Network Joint Research Center for Mate-
rials and Devices’.
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experimental detail) associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.05.001.
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