Ruthenium on Carbon Catalysed Carbon-Carbon Cleavage of Aryl Alkyl Ketones and Aliphatic Aldehydes in Aqueous Media

Article abstract of DOI:10.1002/adsc.201700774

A new ruthenium on carbon-catalysed carbon–carbon (C?C) cleavage reaction of aryl alkyl ketone derivatives in water in the presence of CaO under atmospheric oxygen conditions has been developed. Corresponding benzoic acid derivatives were produced from various aryl alkyl ketones in excellent yields. CaO acts as an adsorbent of CO and CO₂ to maintain a sufficient concentration of oxygen around the catalyst required for effective progress of the reaction. It was also revealed that aliphatic aldehydes were generated from the alkyl moiety of aryl alkyl ketones over the course of the reaction. The aliphatic aldehyde derivatives undergo either an oxidation to the corresponding aliphatic carboxylic acids or a further continuous C?C cleavage reaction to form aliphatic aldehydes with loss of one carbon along with the formation of CO and CO₂. (Figure presented.).

Full text of DOI:10.1002/adsc.201700774

Title: Ruthenium on carbon catalysed carbon-carbon cleavage of aryl
alkyl ketones and aliphatic aldehydes in aqueous media
Authors: Tomohiro Hattori, Hiroki Okami, Tomohiro Ichikawa, Shigeki
Mori, Yoshinari Sawama, Yasunari Monguchi, and Hironao
Sajiki
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700774
Link to VoR: http://dx.doi.org/10.1002/adsc.201700774

10.1002/adsc.201700774
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Ruthenium on carbon catalysed carbon-carbon cleavage of aryl
alkyl ketones and aliphatic aldehydes in aqueous media
Tomohiro Hattori,a,b Hiroki Okami,a Tomohiro Ichikawa,a Shigeki Mori,a Yoshinari
Sawama,a Yasunari Monguchi,a,c* and Hironao Sajikia*
a
Laboratory of Organic Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
Fax: +81-58-230-8109; email: sajiki@gifu-pu.ac.jp.
Molecular Catalyst Research Center, Chubu University, 1200, Matsumoto-cho, Kasugai, Aichi 487-8501, Japan.
Laboratory of Organic Chemistry, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-
b
c
8511, Japan. Fax: +81-92-553-5698; email: monguchi@daiichi-cps.ac.jp
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
and so on, but they have not been applied as C–C
carbon (C–C) cleavage reaction of aryl alkyl ketone bond cleavage catalysts for phenyl alkyl ketones. We
Abstract. A new ruthenium on carbon-catalysed carbon–
derivatives in water in the presence of CaO under
atmospheric oxygen conditions has been developed.
Corresponding benzoic acid derivatives were produced
from various aryl alkyl ketones in excellent yields. CaO
acts as an adsorbent of CO and CO2 to maintain a sufficient
concentration of oxygen around the catalyst required for
effective progress of the reaction. It was also revealed that
aliphatic aldehydes were generated from the alkyl moiety
of aryl alkyl ketones over the course of the reaction. The
aliphatic aldehyde derivatives undergo either an oxidation
to the corresponding aliphatic carboxylic acids or a further
continuous C-C cleavage reaction to form aliphatic
aldehydes with loss of one carbon along with the formation
of CO and CO2.
have developed an additive-dependent regioselective
control method for Pd/C-catalysed C–C cleavage
reactions of cinnamaldehyde derivatives.[4] The
development of a novel and easy C–C bond cleavage
reaction of various compounds has enormous
significance because of the direct route to new
synthetic strategies for the reconstruction of the
chemical structure of molecules.
Herein, we have established a heterogeneous Ru/C-
catalysed C–C bond cleavage reaction of aryl alkyl
ketones in water in the presence of molecular oxygen
as an environmentally friendly solvent and oxidizing
reagent. Moreover, inexpensive CaO was found to
play the role of an adsorbent of CO2 and CO,
significantly increasing the reaction efficiency. Since
the formation of carboxylic acids and alkyl aldehydes
bearing different lengths of alkyl chains were
observed, we focused on the sequentially repeating
C–C bond cleavage reactions of the alkyl aldehydes
derived from aryl alkyl ketones. The proposed
mechanism of the C–C bond cleavage reaction is
described in detail.
Initially, we examined the catalyst activities of
various carbon-supported transition metals (each 5
mol%) for the C–C bond cleavage reaction of
valerophenone in water in an O2 atmosphere (Table
1). Catalysts were evaluated by the comparison of the
material ratio of the recovered valerophenone to
benzoic acid after the reaction (100 °C, 24 h). As a
result, 10% Ru/C was found to be effective and 5%
Ru/C further improved the catalyst activity (Entries 6
and 7), while 10% Pd/C, 10% Pt/C, 10% Rh/C, 10%
Ir/C, and 10% Au/C showed relatively poor catalyst
activities (Entries 1–5).
Keywords: C-C activation; Cleavage reactions;
Heterogeneous catalysis; Oxidation; Ruthenium
Carbon–carbon (C–C) bond cleavage reactions of
molecules have attracted increasing interest in
synthetic organic chemistry because of their
application in industry and laboratories.[1] In
particular, C–C bond cleavage reactions between a
carbonyl carbon and the α-carbon of aryl alkyl
ketones have been reported to produce aryl
carboxylic acids,[2] which could be useful as various
building blocks in the synthesis of natural products,
pharmaceuticals, agricultural chemicals, and dyes.[3]
Some such reactions require the addition of strong
acid,[2a] peroxide,[2b] or CBr4,[2c] which should be
avoided owing to their environmental impacts. Others
use metal catalysts under mild but homogeneous
conditions,[2d,e] where the residual metal in the
products would pose
a
serious problem.
catalysts are
Table 1. Catalyst activity
Heterogeneous transition-metal
attractive because of their stability under atmospheric
conditions, easy handling, recoverability, reusability
1
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10.1002/adsc.201700774
Advanced Synthesis & Catalysis
15
Ca(OH)2 H2O
CaO H2O
Ca(OH)2 H2O
CaCO3 H2O
12
6 : 94
trace : >99
2 : 98
16b)
17b)
12
12
12
18b)
38 : 62
a)
1
b)
Determined by H NMR. 4 equiv of a additives were
used.
Entry
Catalyst
Ratio
(Substrate : Product)a)
1
2
3
4
5
6
7
10% Pd/C
10% Pt/C
10% Rh/C
10% Ir/C
10% Au/C
10% Ru/C
5% Ru/C
91 : 9
91 : 9
Encouraged by these results, we applied the
optimal conditions to the C–C bond cleavage of
various aryl alkyl ketones (Table 3). Benzoic acid
(2a) was obtained in good yields from phenyl alkyl
ketones irrespective of the length of the alkyl moiety
(1a–f). Although the C–C bond cleavage reaction of
2,2-dimethylpropiophenone (1g) did not proceed
significantly, monosubstitution of a methyl group at
the α- or β-position of the carbonyl group of
isobutyrophenone (1e) and isovalerophenone (1f) had
90 : 10
83 : 17
100 : 0
66 : 34
48 : 52
a) Determined by 1H NMR.
The choice of solvent was important for the present
reaction (Table 2). While toluene and alcoholic
solvents, such as MeOH and i-PrOH were
inappropriate (Entries 1–3), the reaction proceeded in
dimethyl sulfoxide (DMSO) and H2O (Entries 4 and
5). H2O was particularly effective. Consequently, a
variety of additives were screened in H2O as the
solvent. Although the addition of acids decreased the
reaction efficiency (Entries 6 and 7), the reaction was
promoted by bases, such as Na2CO3, NaOH, CaO,
and Ca(OH)2 (Entries 8–11). CaO and Ca(OH)2 led to
more than 90% conversion of valerophenone after 12
h (Entries 14 and 15), and the reaction was nearly
completed in 12 h on increasing the amount of CaO
or Ca(OH)2 from 2 equiv to 4 equiv (Entries 16 and
17). The addition of CaCO3 as another Ca salt
resulted in moderate conversion (Entry 18). Finally,
CaO was selected as the appropriate base because of
its general versatility.
a
negligible influence on the yields. The
propiophenone bearing an electron-donating methyl
or methoxy group on the benzene ring (1i and 1j)
could be converted to the corresponding benzoic acid
derivatives, while the lipophilic substrates 1h and 1k
did not react well under the present aqueous reaction
conditions.[5] Moreover, benzyl phenyl ketone
derivatives were also good substrates, and the desired
corresponding carboxylic acid derived from the
benzoyl moiety could be obtained together with
theoretically equimolar benzoic acids originating
from the corresponding benzyl moiety of the
substrates (1l and 1m). Benzoic acid was also
generated from fenipentol (1n), which has a hydroxy
group at the benzyl position of alkyl group instead of
a carbonyl group.[6]
Table 3. Scope of substratea)
Table 2. Effect of additive and solvent
Entry Additive Solvent Time
(h)
Ratio
(Substrate
Product)a)
:
1
‒
MeOH
24
100 : 0
2
3
4
‒
‒
‒
i-PrOH 24
Toluene 24
DMSO 24
100 : 0
100 : 0
81 : 19
5
6
7
8
‒
H2O
H2O
H2O
24
24
24
24
24
24
24
12
12
12
48 : 52
74 : 26
58 : 42
trace : >99
trace : >99
trace : >99
trace : >99
16 : 84
AcOH
TFA
Na2CO3 H2O
NaOH
CaO
Ca(OH)2 H2O
Na2CO3 H2O
9
H2O
H2O
10
11
12
13
14
NaOH
CaO
H2O
H2O
15 : 85
10 : 90
2
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10.1002/adsc.201700774
Advanced Synthesis & Catalysis
a)
b)
Determined by 1H NMR.
Obtained from the 4-
tolylmethyl moiety of 1m.
We examined the internal gas composition in the
reaction vessel after the cleavage reaction of
valerophenone using gas chromatography (GC/TCD)
(Table 4). While 1.5 v/v% of CO and 4.8 v/v% of
CO2 were detected in the absence of CaO (Table 4,
Entry 1), CO and CO2 were hardly detected on the
addition of CaO (Entry 2). In addition, CO underwent
Ru/C-catalysed oxidation to CO2 under an O2
atmosphere.[7] Based on these results, it can be
suggested that CaO functioned not only as a
neutralizer of the resulting acids but also as an
adsorbent of CO2, which suppressed the reaction
progress due to the interference of the smooth contact
between the 5% Ru/C-substrate complex and oxygen
in the reaction vessel by CO2 possessing a
comparatively heavy specific gravity.
Scheme 2. DNPH derivatization
Table 4. GC analysis of CO and CO2
To clarify the mechanism of the C–C cleavage
reaction of aliphatic aldehydes, we conducted several
experiments using heptanal and heptanoic acid as
substrates. Heptanal was smoothly oxidized to
heptanoic acid in water at 100 °C under an O2
atmosphere in the absence of 5% Ru/C and CaO
(Scheme 3, Eq. 1). Since heptanoic acid was totally
tolerant toward the Ru/C-catalysed C–C cleavage
reaction conditions (Eq. 2), CO2 was not generated by
the decarboxylation of aliphatic carboxylic acids. On
the basis of the similar and continuous 5% Ru/C-
catalysed C–C bond cleavage reaction of heptanal,
several smaller aliphatic aldehydes possessing
different lengths of alkyl chains were detected by GC
(Eq. 3). Therefore, valerophenone (1a) was initially
converted to benzoic acid (2a) and butanal (3a),
which partially underwent further oxidation to the
corresponding butanoic acid (4a), and a sequential C–
C cleavage reaction of butanal (3a) occurred to form
propanal (3b) and smaller acetaldehyde and
formaldehyde (undetected), and the corresponding
propionic acid (4b) and smaller acetic acid and
formic acid (undetected).
Entry Additive
CO v/v(%)
1.5
1.0
CO2 v/v(%)
4.8
trace
1
2
‒
CaO
The formation of aliphatic aldehydes 3a and 3b
and aliphatic carboxylic acids 4a and 4b was also
confirmed by GC along with benzoic acid (2a)
(Scheme 1), suggesting that butanal (3a), generated
by Ru/C-catalysed C–C cleavage of valerophenone
(1a), would undergo either oxidation or a further C–C
bond cleavage reaction of 3a to produce butanoic
acid (4a) or propanal (3b), respectively. Furthermore,
2,4-dinitrophenyl hydrazine (DNPH) and H3PO4 in
MeOH was added to the reaction mixture at room
temperature after the Ru/C-catalysed C–C bond
cleavage of valerophenone in H2O for 12 h in the
presence of CaO under an O2 atmosphere, and then
the corresponding hydrazones derived from butanal
(5a), propanal (6a), and acetone (7a) could be
obtained (Scheme 2).
Although C–C bond cleavage reactions based on
the oxidative decarbonylation of 3a and subsequent
further oxidation catalysed by a homogeneous
rhodium,[8] manganese,[9] or iridium-catalyst[10] to
give propanoic acid, acetic acid, and formic acid have
been reported, the related reaction mechanisms have
never been proposed in these reports.
Scheme 3. Cleavage reaction of aliphatic aldehyde and
carboxylic acid
Scheme 1. GC analysis of aldehydes and carboxylic acids
3
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10.1002/adsc.201700774
Advanced Synthesis & Catalysis
According to the mechanism, Ru(0) on Ru/C would
be oxidatively inserted into the O-H bond of the enol
form of valerophenone (1a) to form ruthenium(II)
enolate A. Then, the phenacyl radical B,[12] produced
by homolysis of the O-Ru bond of A, reacts with
molecular oxygen to give the hydroperoxide
intermediate C and Ru(0). Subsequent homolytic
cleavage of the O–O and C–C bonds of C affords
acyl radical D and butanal (E) together with the
hydroxyl radical, and then benzoic acid could be
obtained from D and the hydroxyl radical. Although
butanal (E) is certainly oxidized to the corresponding
butyric acid (F, 1a),[13] E also undergoes Ru/C-
catalysed C–C bond cleavage in a similar manner.
Finally, CO and CO2 would be discharged via Ru/C-
catalysed dehydrogenation of formaldehyde and
formic acid, respectively.
The plausible mechanism of the oxidative C–C
bond cleavage reaction is illustrated in Scheme 4.[11]
Scheme 4. Proposed mechanism 1
4
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10.1002/adsc.201700774
Advanced Synthesis & Catalysis
It is difficult to explain the formation of the DNPH
The homolysis of the C–Ru bond of G would afford a
primary aliphatic radical intermediate H, which is
transformed to propanal via oxidation by molecular
oxygen. On the other hand, H could migrate to a
more stable secondary radical I, and subsequent
oxidation easily provides acetone.
derivative 7a derived from acetone as shown in
Scheme 2 by the mechanism depicted in Scheme 4.
Therefore, we propose an additional possible pathway
in Scheme 5. The oxidative addition of the C(O)–H
bond of butanal (E) to Ru(0) and subsequent Ru-
migration would form a Ru(II) hydride complex G.[4]
Scheme 5. Proposed mechanism 2
In conclusion, we have demonstrated a novel Ru-
catalysed aqueous oxidative C–C cleavage reaction of
aryl alkyl ketones and aliphatic aldehydes. The
reaction provides a practical and mild synthetic
approach to benzoic acid derivatives, because of the
use of molecular oxygen as an oxidant,
heterogeneous Ru/C as the catalyst, and inexpensive
CaO as a base. Although the reaction seems simple, it
includes complicated reaction pathways centred
around Ru/C-catalysed oxidative C–C cleavage
reactions. A plausible radical process is proposed on
the basis of mechanistic studies.
Acknowledgements
This work was partly supported by a Research Fellowship for
Young Scientists of the Japan Society for the Promotion of
Science (Grant number 15J11072). We thank the N.E. Chemcat
Corporation for kindly providing 5% Ru/C.
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Experimental Section
General procedure for benzoic acids derivatives
synthesis (Table 3)
A mixture of 5% Ru/C (25.3 mg, 12.5 μmol), aryl alkyl
ketone derivative (250 μmol), and CaO (56.1 mg, 1 mmol)
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10.1002/adsc.201700774
Advanced Synthesis & Catalysis
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6
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10.1002/adsc.201700774
Advanced Synthesis & Catalysis
COMMUNICATION
Ruthenium on carbon catalysed carbon-carbon
cleavage of aryl alkyl ketones and aliphatic
aldehydes in aqueous media
Adv. Synth. Catal. Year, Volume, Page – Page
Tomohiro Hattori, Hiroki Okami, Tomohiro
Ichikawa, Shigeki Mori, Yoshinari Sawama,
Yasunari Monguchi,* and Hironao Sajiki*
7
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