Direct oxidative coupling of benzenes with acrylonitriles to cinnamonitriles catalyzed by Pd(OAc)2/HPMoV/O2 system

Article abstract of DOI:10.1039/c0ob00176g

A facile direct synthesis of cinnamonitriles from acrylonitriles and benzenes is successfully achieved by using Pd(OAc)₂/HPMoV/O ₂ catalyst system via the direct C-H bond activation of benzenes using molecular oxygen as a terminal oxidant.

Full text of DOI:10.1039/c0ob00176g

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COMMUNICATION
www.rsc.org/obc | Organic & Biomolecular Chemistry
Direct oxidative coupling of benzenes with acrylonitriles to cinnamonitriles
catalyzed by Pd(OAc)2/HPMoV/O2 system†
Yasushi Obora,*a Yoshihisa Okabea and Yasutaka Ishii*b
Received 27th May 2010, Accepted 7th July 2010
First published as an Advance Article on the web 23rd July 2010
DOI: 10.1039/c0ob00176g
A facile direct synthesis of cinnamonitriles from acry-
lonitriles and benzenes is successfully achieved by using
Pd(OAc)2/HPMoV/O2 catalyst system via the direct C–H
bond activation of benzenes using molecular oxygen as a
terminal oxidant.
Pd(II)14 and the oxidative coupling reaction of benzene with
olefins such as acrylate, acrolein, and ethylene was achieved
by using the Pd(II)/HPMoV/O2 system.12 But the reaction of
benzene with acrylonitrile has not yet been successful under
previously reported conditions, giving cinnamonitrile only in low
yield (9%).12b However, it is very important to develop the direct
catalytic method for the activation of the C–H bond of benzene
from the synthetic and mechanistic point of view.
In this communication, we wish to report a facile synthetic
method of cinnamonitriles through the coupling of excess amount
of benzene and acrylonitrile by Pd(II)/HPMoV/O2 catalytic
system. This reaction provides a clean method to cinnamonitriles
from easily accessible mass feedstocks such as benzene and
acrylonitrile using molecular oxygen as terminal oxidant.
The results of the reaction of benzene (1a) with acrylonitrile
(2a) are shown in Table 1 (eqn (1)).
a,b-Unsaturated nitriles are important compounds as a building
block in organic synthesis, because the nitrile group is a key
functionality in natural products, agricultural chemicals, and
biologically active compounds.1 In particular, cinnamonitriles
are important starting materials possessing both the aromatic
group and the reactive a,b-unsaturated nitrile group in synthetic
chemistry.2 Therefore, various methods for preparing the cinna-
monitriles have been reported.3–5 The most widely used method
to synthesize cinnamonitriles is dehydration of cinnamamides or
cinnamaldoximes,4,5 which generally required hazardous, toxic, or
expensive dehydration agents including strong acids and bases.6
The unsaturated nitriles can also be prepared by the Wittig-
type reactions using cyanoalkylphosphates, which produce a large
amount of inorganic salts as wastes.7 Another approach to cinna-
monitrile is the reaction of alcohols with ammonia.8 However,
this reaction calls for the use of a stoichiometric amount of
oxidants such as tert-BuOOH and I2.8 Quite recently, Mizuno and
coworkers reported that the Ru(OH)x/Al2O3-catalyzed catalytic
oxidative reaction of cinmamalcohol (or cinnamaldehyde) and
ammonia using air (6 atm) leading to cinnamonitrile in 82% yield.9
Alternatively, the Pd-catalyzed Mizoroki–Heck reaction of
acrylonitrile with aryl halides is also employed as a useful synthetic
tool for cinnamonitriles.10 However, this method does not avoid
the formation of undesired waste salts arising from the use of
aryl halides and bases. Therefore, the direct oxidative coupling
of benzene with acrylonitrile leading to cinnamonitrile is highly
desirable from the standpoint of green chemistry.
(1)
The reaction of 1a (60 mmol) with 2a (1.5 mmol) catalyzed
by Pd(OAc)2 (0.1 mmol) combined with H4PMo11VO40·22H2O
(HPMo11V) (0.02 mmol) proceeded smoothly in the presence
of small amounts of acetylacetone (0.1 mmol), and NaOAc
(0.1 mmol) under 1 atm of O2 in propionic acid at 90 ◦C
for 5 h to give cinnamonitrile (3a) in 66% yield as a mixture
of streoisomers (E : Z = 75 : 25) along with a trace amount of
b-phenylcinnamonitrile (4a) (entry 1). The yields of the coupling
products (3a and 4a) were markedly affected by the amount
of 1a used. Thus, when 90 mmol of 1a was used toward 2a
(1.5 mmol), the total yield of the oxidative coupling products
was reached to 89% as a mixture of 3a (78%) and 4a (11%)
(entry 2). Fortunately, most of the unreacted benzene using in
excess was easily recovered by simple distillation from a reaction
mixture. On the other hand, the yield of 3a was considerably
decreased to 12% when 30 mmol of 1a was used (entry 3). However,
the yield of 3a was high (68%) when the reaction of 1a (30 mmol)
and 2a (0.75 mmol) was carried out (entry 4). In this reaction,
HPMoV under the influence of molecular oxygen using a terminal
oxidant serve as efficient reoxidation catalysts of the reduced
Pd(0) to Pd(II) during the reaction course. Indeed, the reaction
did not proceed catalytically in the absence of HPMoV(entry 5).
Furthermore, the reaction under argon was sluggish under these
conditions (entry 6). It is noteworthy that the reaction under open
air gave the coupling product 3a in substantial yield (entry 7).
The effect of the HPMoV was examined under the same reaction
conditions as entry 1, Table 1 (entries 8–10).
To date, the oxidative coupling of arenes with olefins through
the direct activation of the C–H bond of arenes is a topic of
current investigation.10–11 Therefore, considerable research works
have been performed by ours and other groups.12–13 As for the
most successful example of this protocol, we have found that
the combination of molybdovanadophosphoric acid (HPMoV)
with O2 serves as an efficient reoxidation system of Pd(0) to
aDepartment of Chemistry and Materials Engineering, Faculty of Chemistry,
Materials and Bioengineering, High Technology Research Center, Kansai
University, Suita, Osaka, 564-8680, Japan. E-mail: obora@kansai-u.ac.jp;
Fax: +81-6-6339-4026; Tel: +81-6-6368-0876
bORDIST, Kansai University, Suita, Osaka, 564-8680, Japan. E-mail:
r091001@kansai-u.ac.jp
† Electronic supplementary information (ESI) available: Figure S1, Tables,
experimental procedures, spectra data, and GC and GC-MS spectra of the
products. See DOI: 10.1039/c0ob00176g
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Table 1 Reaction of benzene (1a) with acrylonitrile (2a) by Pd(II)/HPMoV/O2 system under various conditions.a
Yield/%bc
Entry
Pd-catalyst
1a/mmol
2a/mmol
HPMoV
Base
total (3a+4a)
3a (E : Z)
4a
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(acac)2
Pd(DBA)2
Pd(DBA)2
Pd(OCOCF3)2
PdCl2
60
90
30
30
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
1.5
1.5
1.5
0.75
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
None
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
None
68
89 [82]
12
77
7
6
55
56
35
32
42
Trace
58
49
20
20
17
62
66 [47] (75 : 25)
78 [74] (69 : 31)
12 (72 : 28)
68 (74 : 26)
7 (67 : 33)
2
2
11 [8]
n.d.d
9
3e
4e
5
n.d.d
n.d.d
1
6f
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H5PMo10V2O40∑23H2O
H6PMo9V3O40∑20H2O
H7PMo8V4O40∑22H2O
H3PMo12O40∑24H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
H4PMo11VO40·22H2O
6 (69 : 31)
7g
54 (76 : 24)
55 (75 : 25)
35 (75 : 25)
32 (74 : 26)
42 (74 : 26)
Trace
54 (72 : 28)
49 (73 : 27)
20 (72 : 28)
20 (70 : 30)
17 (67 : 33)
60 (73 : 27)
65 (74 : 26)
23 (75 : 25)
12 (72 : 28)
n.d.d
8
9
1
Trace
n.d.d
Trace
n.d.d
4
10
11
12
13
14
15
16
17h
18h
19
20h
21
22
23i
NaHCO3
Na2CO3
LiOAc
n.d.d
n.d.d
n.d.d
n.d.d
2
CsOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
68
24
3
1
12
n.d.d
n.d.d
2
n.d.d
52
Pd(OAc)2
50 (77 : 23)
a 1a was reacted with 2a in the presence of Pd-catalyst (0.1 mmol), HPMoV (0.02 mmol), Base (0.1 mmol), acetylacetone (0.1 mmol) in EtCOOH
(10 mL) at 90 ◦C for 5 h. b Yields are determined based on 2a used. Numbers in the square bracket show isolated yields. c Cinnamamide was obtained as
by-product (<9%) d Not detected by GC. e EtCOOH (5 mL) was used. f Reaction was performed under argon. g Reaction was performed under open air.
h Reaction was performed without acetylacetone. i Reaction was performed in AcOH (10 mL) instead of EtCOOH.
Table 2 Reaction of aromatic compounds (1) with acrylonitrile (2a) by
The best yield of 3a was obtained when H4PMo11VO40·22H2O
Pd(OAc)2/HPMo11V/O2 system under various conditions.a
was used as the reoxidation catalyst. The catalytic performance
of HPMoV was affected by the vanadium content in the HPMoV
and the increasing the content of V resulted in decreasing the
catalytic activity (entries 8–10). The reaction by the use of 12-
molybdophosphoric acid (HPMo12) not involving V ion led to the
moderate yield of 3a (entry 11).
Yield/%bc
Addition of a small amount of a base such as NaOAc is
indispensible to achieve the reaction.12 Therefore, removing of
NaOAc from the present catalytic system did not produce any
coupling products at all (entry 12). The use of NaHCO3 or Na2CO3
as a base gave the coupling products in slightly lower yields (entries
13–14), while LiOAc and CsOAc were found to be less efficient
than NaOAc (entries 15–16).
The catalytic activity in the present reaction markedly enhanced
by adding a small amount of acetylacetonate (acacH) as a ligand
of the Pd catalyst (entry 1 vs. entry 17). Indeed, when Pd(acac)2
was used as the catalyst, comparable catalytic activity to the
Pd(OAc)2/acacH system was observed (entry 1 vs. entry 18).
Pd(dba)2 also showed high catalytic activity by a combination
with acetylacetone as a ligand (entries 19–20). However, other
palladium catalysts such as Pd(OCOCF3)2 and PdCl2, brought
about low yields of the products (entries 21–22). Among various
solvents examined, propionic acid was found to be the best solvent.
The use of acetic acid led to the decrease of the yield of 3a (entry
23) because a reaction in acetic acid does not make a homogeneous
solution. The reaction in selected solvents such as tert-BuOH and
benzonitrile did not give any desired coupling products.
Entry Ar–H (1)
Total (3+4) 3 (o: m: p)d
4e
1
Benzene
Toluene
Toluene
Toluene
Anisole
68 [47]
58 [47]
73
69
80 [67]
3a 66[47] (-)
4a
2
2
3b 51[43] (23 : 29 : 48) 4b 7[4]
3f
4g
5
3b 66 (23 : 38 : 39)
3b 59 (22 : 38 : 40)
4b
4b 10
7
3c 47[43] (22 : 15 : 63) 4c 33[24]
6
7
Chlorobenzene 29 [28]
p-Xylene 46 [37]
3d 29[28] (36 : 27 : 37) 4d n.d.h
3e 46[37] (-)
4e Trace
a 1 (60 mmol) was reacted with 2a (1.5 mmol) in the presence of Pd(OAc)2
(0.1 mmol), H4PMo11VO40·22H2O (0.02 mmol), NaOAc (0.1 mmol),
acetylacetone (0.1 mmol) in EtCOOH (10 mL) at 90 ◦C for 5 h. b Based
on 2a used. Numbers in the square bracket show isolated yields. c Small
amount of the corresponding cinnamamides were detected by GC (<7%).
d The products were obtained as a mixture of stereoisomers (E:Z ratios are
in the range of 6 : 4 to 8 : 2). e Regiochemistry was not determined. f Toluene
(120 mmol) was used. g Toluene (90 mmol) was used and the reaction time
was 24 h. h Not detected by GC.
The reaction of toluene (1b) with 2a afforded the corresponding
coupling products in 58% total yield as an isomeric mixture
(o-3b : m-3b: p-3b = 23 : 29 : 48) along with a small amount of diaryl
product 4b (entry 2). The yield of the coupling products (3b and
4b) was increased to 73% when the reaction was carried out using
1b (120 mmol) in large excess (entry 3). Prolonged reaction time
Several substituted benzenes were reacted with 2a under the
optimized conditions and the results are shown in Table 2.
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Table 3 Reaction of various arenes (1) with crotononitrile (2b) by
using molecular oxygen as the terminal oxidant. This work was
supported by a Grant-in-Aid for Scientific Research from MEXT,
Japan.
Pd(OAc)2/HPMo11V/O2 system (under selected conditions).a
References
Yield/%b
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787and references therein.
Entry
Ar–H (1)
(o: m: p)c
1
Benzene
Toluene
Anisole
Chlorobenzene
p-Xylene
5a
5b
5c
5d
5e
49 [42] (-)
2d
3
53 [53] (21 : 43 : 36)
63 [58] (13 : 23 : 64)
51 [47] (35 : 30 : 35)
49 [43] (-)
4d
5d
a 1 (60 mmol) was reacted with 2b (1.5 mmol) in the presence of Pd(OAc)2
(0.1 mmol), H4PMo11VO40·22H2O (0.02 mmol), NaOAc (0.1 mmol),
acetylacetone (0.1 mmol) in EtCOOH (10 mL) at 90 ◦C for 5 h. b Based
on 2b used. Numbers in the square bracket show isolated yields. c The
products were obtained as a mixture of stereoisomers (E:Z ratios are in
the range of 1 : 1 to 3 : 7). d Reaction time was 15 h.
6 (a) Recently, several catalytic dehydration methods were reported, see:
H.-S. Kim, S. H. Kim and J. N. Kim, Tetrahedron Lett., 2009, 50, 1717;
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Org. Lett., 2002, 4, 2369and references therein.
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K. V. S. Ranganath and T. Athar, Adv. Synth. Catal., 2006, 348, 1977;
(b) S. Burking, B. M. Paine, D. Nama, V. S. Brown, M. F. Mahon, T. J.
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was also effective to increase the yield of 3b in the reaction of 1b
with 2a (entry 4).
The reactivity of anisole (1c) in the present reaction was
considerably high and the corresponding coupling products (3c
and 4c) were obtained in 80% total yield (entry 5). The reaction of
chlorobenzene (1d) with 2a gave lower yield of products (entry 6).
The reaction of p-xylene (1e) gave the monoarylated product (3e)
as a major product (entry 7).
The reaction could be successfully extended to the reaction of
arenes (1) with crotononitrile (2b) and the results are shown in
Table 3. The reaction of benzene with 2a gave b-methylcinnamo-
nitrile (5a) as a mixture of stereoisomer (E : Z = 32 : 68). The
reaction of toluene (1b) with 2b under optimized conditions
afforded a mixture of structural and stereoisomers (5b) (o: m: p =
21: 43 : 36) in 53% yield (entry 2). Similarly, the reaction of anisole
(1c), chlorobenzene (1d), and p-xylene (1e) gave the corresponding
oxidative coupling products (5b–5e) in 49–63% yields (entries 3–5).
A detailed reaction mechanism remains to be further elucidated,
but the reaction course would be explained rationally by a pathway
similar to that proposed by ours12 and Kitamura/Fujiwara group
(Figure S1 in ESI†).13b Namely, the initial electrophilic attack of a
Pd(II) to arene 1 would lead to a s-aryl-palladium(II) intermediate
(A) followed by the insertion of acrylonitriles 2 to A gives s-alkyl-
palladium(II) intermediate B. Subsequently, b-hydride elimination
of the B gives the cinnamonitriles 3 along with Pd–H intermediate.
The Pd–H intermediate is reduced to Pd(0), and the resulting Pd(0)
species is reoxidized by the HPMoV/O2 system to generate Pd(II)
species, as we previously reported.12,14 In this reaction, the use of
less amount of benzene may preferentially subject to coordination
of acrylonitrile to Pd in prior to benzene activation by Pd.
In conclusion, we have developed the direct route to cinnamoni-
triles from acryronitrile and benzenes by Pd(II)/HPMo11V/O2 sys-
tem. This method provides a clean route to various cinnamonitriles
from fundamental chemicals like benzenes and acrylonitriles by
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This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 4071–4073 | 4073
©