Environmentally friendly one-pot synthesis of α-alkylated nitriles using hydrotalcite-supported metal species as multifunctional solid catalysts

Article abstract of DOI:10.1002/chem.200600317

A ruthenium-grafted hydrotalcite (Ru/HT) and hydrotalcite-supported palladium nanoparticles (Pd_nano/ HT) are easily prepared by treating basic layered double hydroxide, hydrotalcite (HT, Mg₆Al ₂(OH)₁₆CO₃) with aqueous RuCl ₃·n H₂O and K₂[PdCl₄] solutions, respectively, using surface impregnation methods. Analysis by means of X-ray diffraction, and energydispersive X-ray, electron paramagnetic resonance, and X-ray absorption fine structure spectroscopies proves that a monomeric Ru^IV species is grafted onto the surface of the HT. Meanwhile, after reduction of a surface-isolated Pd^II species, highly dispersed Pd nanoclusters with a mean diameter of about 70 A is observed on the Pd_nano/HT surface by transmission electron microscopy analysis. These hydrotalcite-supported metal catalysts can effectively promote α-alkylation reactions of various nitriles with primary alcohols or carbonyl compounds through tandem reactions consisting of metal-catalyzed oxidation and reduction, and an aldol reaction promoted by the base sites of the HT. In these catalytic α-alkylations, homogeneous bases are unnecessary and the only by-product is water. Additionally, these catalyst systems are applicable to one-pot syntheses of glutaronitrile derivatives.

Full text of DOI:10.1002/chem.200600317

DOI: 10.1002/chem.200600317
Environmentally Friendly One-Pot Synthesis of a-Alkylated NitrilesUsing
Hydrotalcite-Supported Metal SpeciesasMultifunctional Solid Catalysts
Ken Motokura,[a] Noriaki Fujita,[a] Kohsuke Mori,[b] Tomoo Mizugaki,[a] Kohki Ebitani,[a]
Koichiro Jitsukawa,[c] and Kiyotomi Kaneda*[a]
Abstract: A ruthenium-grafted hydro-
talcite (Ru/HT) and hydrotalcite-sup-
monomeric RuIV species is grafted onto
the surface of the HT. Meanwhile, after
reduction of a surface-isolated PdII spe-
cies, highly dispersed Pd nanoclusters
with a mean diameter of about 70 Š is
observed on the Pdnano/HT surface by
transmission electron microscopy anal-
metal catalysts can effectively promote
a-alkylation reactions of various ni-
triles with primary alcohols or carbonyl
compounds through tandem reactions
consisting of metal-catalyzed oxidation
and reduction, and an aldol reaction
promoted by the base sites of the HT.
In these catalytic a-alkylations, homo-
geneous bases are unnecessary and the
only by-product is water. Additionally,
these catalyst systems are applicable to
one-pot syntheses of glutaronitrile de-
rivatives.
ported palladium nanoparticles (Pdnano
/
HT) are easily prepared by treating
basic layered double hydroxide, hydro-
talcite (HT, Mg6Al2(OH)16CO3) with
aqueous RuCl3·nH2O and K2ACHTER[UNG PdCl4]
solutions, respectively, using surface
impregnation methods. Analysis by
means of X-ray diffraction, and energy-
dispersive X-ray, electron paramagnetic
resonance, and X-ray absorption fine
structure spectroscopies proves that a
ysis.
These
hydrotalcite-supported
Keywords: alkylation
neous catalysis hydrotalcite
nitriles · palladium · ruthenium
· heteroge-
A
·
·
Introduction
bases, and production of large amounts of waste (low atom
efficiency). With ever-increasing environmental concerns,
catalytic a-alkylation of nitriles using alcohols or carbonyl
compounds instead of halides is a desirable protocol for
both laboratory and industrial synthetic chemistry.[2] Grigg
and co-workers demonstrated the a-alkylation of phenylace-
tonitriles with primary alcohols using homogeneous Ru and
Rh complexes in the presence of bases.[3] However, these re-
ported reaction systems suffer from lowcatalytic activity,
significant limitation of substrate scope, and the necessity of
using stoichiometric amounts of inorganic bases as additives.
In addition, the use of homogeneous metal catalysts on an
industrial scale leads to practical problems owing to the dif-
ficulties involved in recovering the expensive metals and li-
gands from the reaction mixture and in separation of prod-
ucts. There is a strong need for development of an environ-
mentally friendly heterogeneous catalyst system for a-alkyl-
a-Alkylated nitriles are important building blocks for syn-
thesizing amides, carboxylic acids, ketones, and a variety of
biologically active agents.[1] The main method for the syn-
thesis of a-alkylated nitriles has been stoichiometric reac-
tion of nitriles with alkyl halides using homogeneous inor-
ganic bases such as NaH and NaNH2 (Scheme 1 A). These
traditional a-alkylations have serious drawbacks: toxicity of
halogenated substrates, the use of homogeneous strong
[a] Dr. K. Motokura, N. Fujita, Dr. T. Mizugaki, Dr. K. Ebitani,
Prof. Dr. K. Kaneda
Department of Materials Engineering Science
Graduate School of Engineering Science, Osaka University
1–3 Machikaneyama, Toyonaka, Osaka 560–8531 (Japan)
Fax : (+81)6-6850-6260
E-mail: kaneda@cheng.es.osaka-u.ac.jp
AHCTREUNG
[b] Dr. K. Mori
Division of Materials and Manufacturing Science
Graduate School of Engineering, Osaka University
1–2 Yamadaoka, Suita, Osaka 565–8071 (Japan)
droxides of Mg and Al. The HTs have received much atten-
tion as advanced materials because of their unique proper-
ties, such as the cation exchange ability of the Brucite layer,
anion exchange ability of the interlayer, surface tunable ba-
sicity, and adsorption capacity.[4,5] The development of
highly functionalized HT catalysts for a variety of organic
[c] Prof. Dr. K. Jitsukawa
Department of Materials Science and Engineering
Graduate School of Engineering
Nagoya Institute of Technology
Gokiso-cho, Showa-ku, Nagoya 466–8555 (Japan)
8228
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FULL PAPER
firmed that the Ru species were deposited onto the HT sur-
face. The K-edge X-ray absorption near-edge structure
(XANES) spectrum of the Ru species on the Ru/HT was
similar to that of [RuO2] but different from that of [Ru-
AHCTRE(UNG acac)3], and the Ru/HT was EPR silent (EPR = electron
paramagnetic resonance). These results showthat the Ru
species of the Ru/HT is in the +4 oxidation state.[12] The ab-
sence of chlorine on the Ru/HT was confirmed by X-ray
photoelectron spectroscopy (XPS) and energy-dispersive X-
ray (EDX) analysis. In Fourier transform (FT) of the k3-
weighted Ru K-edge X-ray absorption fine structure
(EXAFS) spectrum of the Ru/HT, a peak near 3.5 Š corre-
Scheme 1.
À
transformations has already been reported by our group and
others.[6,7] For example, the surface basicities of the HTs
result in high catalytic activities for the epoxidation of ole-
fins,[6a,b] N-oxidation of pyridines,[6c] and carbon–carbon
bond-forming reactions.[6d–g] Additionally, the introduction
of transition-metal species, such as Ru,[7a–c] Mn,[7c] Pd,[7d–g]
W,[7h,i] Os,[7j] Ni,[7k,l] or Cu,[7m,n] into the Brucite layer or solid
surface of the HTs could afford high-performance supported
metal catalysts. From these results, HT-supported metal
compounds have potential as excellent multifunctional cata-
lysts containing both surface base sites and transition-metal
species as active centers for one-pot sequential reac-
tions.[7d,8,9,10] In this context, we present the synthesis and
characterization of a ruthenium-grafted hydrotalcite (Ru/
HT) and hydrotalcite-supported palladium nanoparticles
(Pdnano/HT) for efficient a-alkylation of nitriles with primary
alcohols (Scheme 1 B) and carbonyl compounds (Scheme
1 C). Since these catalysts possess both strong surface basici-
ties and oxidation/reduction abilities based on the surface
metal species, one-pot formation of a-alkylated nitriles
could be achieved through several tandem reactions. This
report also includes the further transformation of a-alkylat-
ed nitriles to glutaronitrile derivatives in a single reactor.[1b,e]
sponding to Ru Ru bonds was barely observed (Figure 1).
Figure 1. Fourier-transform (FT) of k3-weighted Ru K-edge EXAFS of
the Ru/HT.
The coordination number (CN), bond length (R), and
Debye–Waller factor (Ds) of the Ru O and Ru Mg bonds
were estimated by a curve-fitting analysis (Table 1). The
À
À
Table 1. Curve-fitting results of Ru K-edge EXAFS of the Ru/HT.
Shell
CN[a]
R[b] [Š]
Ds[c] [Š2]
À
Ru O(1)
3.0
2.3
0.9
1.5
1.97
2.04
1.82
3.18
0.0022
0.0006
0.0064
0.0060
Results and Discussion
À
Ru O(2)
À
Ru O(3)
Catalyst preparation and characterization: Surface impreg-
nation is one of the most simple and efficient protocols for
the introduction of active species onto solid supports.[11] Be-
cause of the high adsorption capacity of the HT, a variety of
catalytically active metals can easily be created on the HT
surface.
À
Ru Mg
[a] Coordination number. [b] Interatomic distance. [c] Ds is the differ-
ence between the Debye–Waller factor of the samples and that of the ref-
erence sample.
À
length of the shortest Ru O bond (1.82 Š) was comparable
Ru/HT: In our previous work on hydrotalcite-supported Ru
catalysts for aerobic oxidation of alcohols, Ru species placed
on the solid HT surface showed higher activity than those in
the inner HT framework owing to the ease of accessibility
of substrates to the metal centers.[9a–c] Preparation of the cat-
alyst by introducing active Ru species onto the hydrotalcite
surface takes place as follows: Treatment of the HT with an
aqueous solution of RuCl3·nH2O at room temperature af-
to that of
a
RuIV OH moiety (1.79 Š) observed in
À
[RuIV(OH)
(TDCPP)].[13] The Ru O distance of 2.04 Š is
À
close to the bond length between a Ru cation and an
oxygen atom in an aqua ligand.[14] Conclusively, a monomer-
ic RuIV species with one hydroxy and two aqua ligands was
grafted onto a triad of oxygen atoms on the HT surface, as
illustrated in Figure 2.[15]
forded the Ru/HT as
a
gray powder (Ru content
Pd/HTs: The hydrotalcite-supported palladium nanoparti-
cles (Pdnano/HT) can be synthesized by simple surface im-
pregnation followed by reduction.[16] A mixture of the solid
0.05 mmolgÀ1). Retention of the original HT interlayer dis-
tance (3.0 Š), as shown by X-ray diffraction (XRD), con-
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K. Kaneda et al.
Figure 2. A proposed surface structure around RuIV of the Ru/HT.
HT and an aqueous solution of K2ACHTRE[UNG PdCl4] was stirred at
room temperature under air to form a pale yellowpowder
(PdII/HT), which was then successively reduced in the pres-
ence of 1 atm H2 at 1008C to afford the Pdnano/HT as a black
powder (Pd content: 0.1 mmolgÀ1). The retention of the HT
interlayer distance (3.0 Š) in the PdII/HT and Pdnano/HT
were confirmed by XRD. In UV/Vis/DRS measurement, the
peak corresponding to PdII species at 280 nm disappeared
after reduction of the PdII/HT. The shapes of Pd K-edge
XANES spectra of the PdII/HT and Pdnano/HT were similar
Figure 4. Fourier transforms of k3-weighted Pd K-edge EXAFS experi-
mental data for A) PdII/HT, B) Pdnano/HT, C) Pd foil, and D) Pd oxide.
Phase shift was not corrected.
to those of PdACHTREUNG(OAc)2 and Pd foil, respectively (Figure 3).
verse FT of the peaks at around 1–2 Š for the PdII/HT was
À
well fitted with two types of oxygen atoms at Pd O distan-
À
ces of 1.98 and 2.10 Š (Table 2). The slightly longer Pd O
Table 2. Curve-fitting analysis for the Pd/HT catalysts.[a]
[b]
Sample
PdII/HT
Shell
CN
R[c] [Š]
Ds[d] [Š2]
À
Pd O(1)
2.03
2.00
8.75
1.98
2.10
2.75
0.005
0.002
0.072
À
Pd O(2)
À
Pdnano/HT
Pd Pd
[a] Inverse Fourier transformations were performed for the regions of
1.2–2.0 Š in PdII/HT and 2.0-2.9 Š in Pdnano/HT. [b] Coordination
number. [c] Interatomic distance. [d] Difference between Debye–Waller
factor of Pd/HTs.
À
bond (2.10 Š) was similar to the Pd OH2 bond (2.095 Š) in
[PdII
(NO3)
2A
reasonable surface structure for the PdII/HT is shown in
Figure 5. The inverse FT of the single peak at 2.5 Š due to
À
the Pd Pd bond in the Pdnano/HT revealed a metallic form,
with an R of 2.75 Š and a CN of 8.75, respectively, as listed
in Table 2. The smaller CN value relative to that of Pd foil
Figure 3. Pd K-edge XANES spectra of A) PdII/HT, B) Pdnano/HT, C) Pd
foil, and D) [Pd(OAc)2].
ACHTREUNG
The FTs of k3-weighted EXAFS data are depicted in
À
Figure 4. Peaks due to Pd Pd bonds in the second coordina-
tion sphere, detectable in those of Pd foil at around 2.5 Š,
were observed for the Pdnano/HT but not for the PdII/HT.
These results suggest that the PdII species on the HT surface
were reduced to Pd0. In EDX analysis, neither chlorine nor
potassium was detected in the PdII/HT or Pdnano/HT. The in-
Figure 5. A proposed structure around PdII species of the PdII/HT.
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a-Alkylated Nitriles
FULL PAPER
(12) demonstrated the formation of Pd nanoclusters. From
transmission electron microscopy (TEM) analysis, highly
dispersed Pd nanoclusters with a mean diameter of about
70 Š (standard deviation 14 Š) were observed on the Pdnano
HT surface.
/
lyzed a-alkylation of nitriles using alcohols as alkylating re-
agents.[19]
Synthesis of a,b-unsaturated nitriles from nitriles and pri-
mary alcoholsunder O atmosphere: We have previously re-
A model a-alkylation of 1a with a large excess of ethanol
(2a) was studied in the presence of various supported Ru
catalysts (Table 4). Only the Ru/HT showed high catalytic
activity, giving a-ethylated phenylacetonitrile in 98% yield
(Table 4, entry 1). Other solid base-supported Ru catalysts,
such as Ru/Al2O3, Ru/MgO, Ru/Al(OH)3, and Ru/Mg(OH)2,
were less active under the present reaction conditions
(Table 4, entries 2–5). The a-alkylation did not occur at all
in the presence of only parent HT or RuCl3·nH2O (Table 4,
entries 7, 8).
2
ported hydrotalcite-supported ruthenium-catalyzed oxida-
tion of alcohols to carbonyl compounds using molecular
oxygen as a sole oxidant.[7a–c,18] Furthermore, it is well
known that the surface base sites of the HT promote the
aldol reaction of nitriles with aldehydes.[5,6e–f] These results
encouraged us to develop a one-pot synthesis of a,b-unsatu-
rated nitriles from alcohols and nitriles, using the Ru/HT
catalyst, by consecutive Ru-catalyzed aerobic oxidation/
base-catalyzed aldol condensation (Table 3). The oxidation
Table 3. One-pot synthesis of a,b-unsaturated nitriles using the Ru/HT
Table 4. a-Ethylation of 1a using various catalysts.[a]
under O2 atmosphere.[a]
Entry
Nitrile
Alcohol
Product
Isolated
Entry
Catalyst
Yield of 3a [%][b]
yield [%][b]
1
Ru/HT
98
2
3
4
5
Ru/Al2O3
Ru/MgO
Ru/Al(OH)3
Ru/Mg(OH)2
Pdnano/HT
HT
14
2
5
2
trace
N.R.
N.R.
1
2
3
1a
1a
1a
R = H
R = Cl
R = OMe
R = H
R = Cl
R = OMe
98
98
95
6
7[c]
8[d]
RuCl3·nH2O
4[c]
1a
1a
93
93
[a] Reaction conditions; 1a (1 mmol), 2a (2 mL), catalyst (0.15 g,
0.075 mmol of metal), 20 h, 1808C, Ar. [b] Determined by GC. Based on
1a used. [c] 0.15 g of HT was used. [d] 0.0075 mmol of Ru was used.
5[d]
6[e]
7[e]
R = H
R = H
82
80
Syntheticscope : On the basis of the highest catalytic activity
of the Ru/HT, we examined a-alkylations involving a variety
of nitriles with aliphatic and aromatic alcohols using this cat-
alyst, as shown in Table 5. In many reactions of aryl acetoni-
triles with ethanol (Table 5, entries 1–7), the corresponding
ethylated products were formed in excellent yields, except
for the case of 2-pyridinylacetonitrile (Table 5, entry 7).
Electronic variation in the p-substituted phenylacetonitrile
did not strongly affect the yields of the products (Table 5,
entries 1–4). A sterically hindered 1-naphthylacetonitrile
(Table 5, entry 5) and a nitrile containing a thiophene ring
(Table 5, entry 6) were also readily reacted. To extend the
scope of the alcohols employed in the Ru/HT-catalyzed a-
alkylation of nitriles, methanol, n-butanol, isobutanol, and
benzyl alcohol were investigated as potential primary alco-
hols. All of these substrates underwent the desired alkyla-
tion to afford important organic agents (Table 5, entries 10–
13): for example, 2-phenylhexanenitrile, a precursor of the
systemic fungicide Systhane,[1c] was obtained in 86% isolat-
ed yield from n-butanol (Table 5, entry 11). It is noteworthy
that this catalyst system was applicable to a 20 mmol-scale
[a] Reaction conditions; i) alcohol (1 mmol), toluene (3 mL), Ru/HT
(0.3 g; Ru: 0.015 mmol), 808C, 2 h, O2 (1 atm). ii) Nitrile (1.1 mmol),
1208C, 2 h, Ar. [b] Based on alcohol used. [c] i) 6 h. [d] i) 3 h. [e] ii) 808C,
1 h.
reaction of benzyl alcohol proceeded under molecular
oxygen at atmospheric pressure to afford benzaldehyde in
quantitative yield. Subsequent addition of phenylacetonitrile
1a gave (Z)-2-phenylcinnamonitrile in 98% yield (Table 3,
entry 1). Several heteroaromatic alcohols also reacted
smoothly (Table 3, entries 4 and 5). This consecutive method
was applicable to active nitriles such as ethyl cyanoacetate
1b (Table 3, entry 6) and malononitrile (Table 3, entry 7).
a-Alkylation of nitrileswith primary alcoholsusing the Ru/
HT catalyst: Interestingly, the reaction of 1a with benzyl al-
cohol using the Ru/HT afforded an a-benzylated nitrile, 2,3-
diphenylpropionitrile, as a sole product under Ar atmos-
phere [Eq. (1)]. This result led us to explore the Ru-cata-
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K. Kaneda et al.
Table 5. The Ru/HT-catalyzed a-alkylation of nitriles with primary alcohols.[a]
trile, which suggests that the
strong coordination of highly
acidic nitriles to the Ru species
depressed the desired a-alkyl-
Entry
Nitrile
Alcohol
Product
Isolated yield [%][b]
AHCTREaGNU tion. In the case of ethyl cya-
noacetate with benzyl alcohol,
an undesirable base-catalyzed
1
2
R = H 1a
R = Me
R = OMe
R = Cl
EtOH 2a
R = H
94
99
92
77
transesterification
product,
2a
2a
2a
R = Me
R = OMe
R = Cl
benzyl
cyanoacetate, was
3[c]
4
formed as
a
major product
(Table 5, entry 14). These re-
sults showthat alcohols are not
5
2a
89
favorable as alkylCAHTREaUNG ting re-
agents for the reaction of cya-
noesters.
6[c]
2a
2a
86[d]
37
Mechanistic investigations: The
reaction of (Z)-2-phenylcinna-
monitrile with benzyl alcohol
using the Ru/HT under an Ar
atmosphere afforded a 98%
yield of 2,3-diphenylpropioni-
trile along with benzaldehyde
(Scheme 2A). On the other
hand, aldol condensation of
phenylacetonitrile with benzal-
dehyde was promoted by the
parent HT catalyst as well as
the Ru/HT, producing (Z)-2-
phenylcinnamonitrile (Scheme
2B). Additionally, in the a-al-
kylation of phenylacetonitrile
7
8
9
2a
2a
trace
trace
10
1a
1a
1a
MeOH
65[d]
86
11
12[c]
85[d]
13[d]
1a
1b
77
14[e,f]
trace[g]
[a] Reaction conditions; nitrile (1 mmol), alcohol (2 mL), Ru/HT (0.15 g, Ru: 0.0075 mmol), 1808C, 20 h, Ar.
[b] Based on nitrile used. [c] Ru/HT (0.3 g, Ru: 0.015 mmol) was used. [d] Determined by GC using internal
standard. [e] 2 mL of toluene and 1.5 mmol of alcohol were used. [f] At 1008C. [g] Benzyl cyanoacetate was
formed in a 37% yield.
with
(C6D5CD2OH),
nyl-3-[D]-3-[D5]-phenylpropio-
nitrile and 2-phenyl-3,3-[D2]-3-
[D5]-phenylpropionitrile were
benzyl-[D7]-alcohol
2-[D]-2-phe-
AHCTREUNG
AHCTREUNG
AHCTREUNG
reaction of phenylacetonitrile with ethanol to afford 2-phe-
nylbutyronitrile in 82% yield with a TOF of 14 hÀ1 and a
TON of 412 [Eq. (2)]. The above values are considerably
obtained (Scheme 3). From these results, a plausible reac-
tion pathway through three consecutive reactions was de-
duced and is illustrated as Scheme 4: i) oxidative dehydro-
higher than those previously reported for reactions using ho-
mogeneous Ru catalysts combined with a stoichiometric
amount of Na2CO3 (TOF 0.77 hÀ1; TON 18).[3]
Unfortunately, the Ru/HT-catalyzed alkylation of nitriles
with low pKa values (11~13), such as malononitrile (Table 5,
entry 9) and 1b (Table 5, en-
Scheme 2.
tries 8 and 14), did not occur.
In a separate experiment, the
reaction of phenylacetonitrile
with ethanol gave no product
in the presence of malononi-
Scheme 3.
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a-Alkylated Nitriles
FULL PAPER
tained in the a-alkylation of phenylacetonitrile with n-buta-
nol (Table 5, entry 11). Since the concentrations of alde-
hydes were kept low, formation of the self-aldol products
was effectively depressed. Finally, the present one-pot pro-
AHCTREcUNG ess achieved the hydrogen transfer-reaction without any
waste, because the aldehydes were consumed as alkylating
reagents. The advantages of sequential reactions in a single
reactor include operational simplicity as well as the achieve-
ment of novel synthetic routes.[8]
a-Alkylation of nitrileswith carbonyl compoundsuisng the
Pdnano/HT catalyst: As described above, the Ru/HT catalyst
could efficiently promote a-alkylation of aryl acetonitriles
with primary alcohols, but reaction of nitriles with low pKa
values, such as malononitrile, cyanoesters, and 2-pyridinyl-
Scheme 4.
genation of alcohols to aldehydes along with the formation
ACHTREaUNG cetonitrile barely occurred owing to strong coordination to
À
of Ru H species; ii) aldol condensation of nitriles with alde-
the Ru species. Because of the synthetic utility of a-alkylat-
ed products from such active nitriles, we aimed to develop
newsynthetic routes to these a-alkylated nitriles using the
Pdnano/HT. The planned reaction sequence was an aldol reac-
tion of nitriles with carbonyl compounds at base sites on the
HT surface, followed by hydrogenation of the a,b-unsaturat-
ed nitriles with Pd species [Eq. (3)].[25,26]
hydes, giving a,b-unsaturated nitriles, at the base sites on
the HT surface; iii) hydrogenation of a,b-unsaturated ni-
[20,21]
À
triles by the Ru H species;
and iv) formation of a-alky-
lated nitriles.[22] The IR spectrum of the benzyl alcohol-treat-
ed Ru/HT catalyst showed a signal at 2120 cmÀ1, which is as-
[23]
À
signed to n
A
an a,b-unsaturated nitrile under molecular oxygen (Table 3),
À
this Ru H species spontaneously reacts with O2 to give the
a,b-unsaturated nitrile exclusively without the correspond-
ing saturated nitrile.
In the initial study, the aldol reaction of ethyl cyanoace-
tate 1b with benzaldehyde 4 was examined using various
solid catalysts (Table 6). The highest yield of an a,b-unsatu-
rated nitrile, (E)-ethyl-2-cyano-3-phenylacrylate 5, was ob-
tained using the HT (Table 6, entry 1). The use of aluminum
oxide resulted in a moderate yield (Table 6, entry 3) and
other solid catalysts were inactive (Table 6, entries 4–7). The
Pdnano/HT was also found to be an efficient catalyst for the
aldol reaction (Table 6, entry 2).
Next, the catalytic activity of the Pdnano/HT for hydroge-
nation of 5 was compared with those of various supported
palladium catalysts, as shown in Table 7. The Pdnano/HT was
an effective catalyst, affording an excellent yield of 3b
Figure 6. IR spectra of the samples A) after treatment of the Ru/HT with
*
*
benzyl alcohol, B) fresh Ru/HT; :Ru-H species, : benzyl alcohol.
Table 6. Aldol reaction of 1b with 4 using various solid base catalysts.[a]
The above-described combination of oxidative dehydro-
genation, aldol condensation, and hydrogenation in a single
reactor has the following advantages over multistep proce-
dures. First, the hydrogen-transfer reaction using the Ru/HT
under Ar gave no over-oxidation products, while oxidation
of primary alcohols using molecular oxygen or hydrogen
peroxide often produces carboxylic acids as by-products.[24]
Next, the cross-aldol reaction of relatively unreactive aryl
acetonitriles with aldehydes that have a-protons of carbonyl
groups often affords undesirable by-products: in a separate
experiment, an aldol reaction of phenylacetonitrile with n-
butyraldehyde formed the corresponding self-condensed
product of the aldehyde, whereas no by-product was ob-
Entry
Catalyst
Yield of 5 [%][b]
1
2
3
4
5
6
7
HT
99
99
52
3
N.R.
2
Pdnano/HT
[c]
Al2O3
MgO
[d]
SiO2
Al(OH)3
Mg(OH)2
2
[a] Reaction conditions; 1b (1.0 mmol), 4 (1.0 mmol), catalyst (0.025 g),
toluene (3 mL), 808C, 1 h, Ar. [b] Determined by GC. [c] JRC-ALO-4.
[d] JRC-SiO-5.
Chem. Eur. J. 2006, 12, 8228 – 8239
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K. Kaneda et al.
Table 7. Hydrogenation of a,b-unsaturated nitrile 5 with various cat
ACHTREUNG
lysts.[a]
ACHTREaUNG -
ide groups, and a pyridine ring (Table 8, entries 1 and 7–11).
Notably, some unreactive nitriles in the Ru/HT catalyst
system were successfully transformed to highly useful inter-
mediates for pharmaceutical synthesis. For example, 3-
phenyl-2-(2-pyridyl)propionitrile, a precursor of antiarrhyth-
mic agents, was obtained from 2-pyridinylacetonitrile with 4
in quantitative yield (Table 8, entry 11), while the traditional
method using benzyl chloride instead of 4 in the presence of
NaNH2 resulted in a 52% yield.[27] This catalyst system was
applicable to 15 mmol-scale synthesis; the reaction of ethyl
cyanoacetate with benzaldehyde proceeded smoothly, and
the crude product was purified by simple distillation to
afford a 95% isolated yield of the product with a TON of
2380 [Eq. (4)]. As described above, the HT is a solid strong
base catalyst that can promote aldol reactions of various ni-
triles with a wide range of pKa values (pKa = 11–22);[28]
however, simple alkane nitriles with high pKa values
(~31)[28] did not react.
Entry
Catalyst
Yield of 3b [%][b]
1
Pdnano/HT
98
76
99
94
49
41
24
trace
trace
2[c]
3
PdII/HT
Pd/Al2O3 (0.5 wt%)[d]
Pd/carbon (0.5 wt%)[d]
Pd/carbon (5.0 wt%)[e]
Pd/MgO
4
5
6
7
8
9
Pd/SiO (0.5 wt%)[d]
Ru/HT
HT
[a] Reaction conditions; 5 (1 mmol), catalyst (1 mol%), H2 (1 atm), tol-
uene (3 mL), 608C, 1 h, H2 (1 atm). [b] Determined by GC. [c] 808C.
[d] Purchased from N.E. Chemcat. [e] Purchased from Wako Pure Chem-
icals.
(Table 7, entry 1), while the
PdII/HT afforded a moderate
yield of the product (Table 7,
entry 2). Several commercially
available supported Pd cata-
lysts, such as Pd/Al2O3 and Pd/
carbon (0.5 wt%), were also
effective in promoting the hy-
drogenation reaction (Table 7,
entries 3 and 4). Pd/MgO and
Pd/SiO2 showed low activities
(Table 7, entries 6 and 7), and
the Ru/HT, in particular, was
not effective at all (Table 7,
entry 8).
Table 8. a-Alkylation of various nitriles with benzaldehydes using the Pdnano/HT.[a]
Entry
Nitrile
Aldehyde
Time of (ii)
[h]
Product
Isolated
yield [%]
1
2
1b
1b
1
3
94
95
3
1b
1b
1b
1b
2
3
9
4
90
Syntheticscope : The generality
of the Pdnano/HT-catalyzed a-
alkylation of various nitriles
with benzaldehydes is illustrat-
ed in Table 8. Both electron-
rich and electron-deficient
benzaldehydes serve as good
substrates, affording the corre-
sponding a-benzylated ethyl
cyanoacetates (Table 8, en-
tries 1–5). Chloro and nitro
groups were reduced under
present reaction conditions
(Table 8, entries 6 and 7); for
example, the reaction of phe-
nylacetonitrile with 4-nitro-
4
99
5
83
6[b]
87[c]
7[d]
1a
23
84[c]
8
4
4
4
5
4
2
82[c]
64
9[b,e]
10
98
11
4
4
2.5
4
99
83
ACHTREUNGbenzaldehyde gave 3-(4-amino-
phenyl)-2-phenylpropionitrile
in high yield (Table 8, entry 7).
A variety of nitriles could be
used as donors, leaving intact
ester, cyano, amide, and sulfox-
12[d]
1a
[a] Reaction conditions; (i) nitrile (1 mmol), carbonyl compounds (1 mmol), Pdnano/HT (0.1 g; Pd: 0.01 mml),
toluene (3 mL), 2 h, 808C, Ar. (ii) 608C, H2 (1 atm). [b] DMF (3 mL) was used as solvent. [c] Determined by
GC using an internal standard. [d] At 1208C for aldol reaction. [e] 18 h for aldol reaction.
8234
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a-Alkylated Nitriles
FULL PAPER
Table 9. a-Alkylation of 1b with various carbonyl compounds using the Pdnano/HT.[a]
The a-alkylation of 1b
with 4 was examined using
various solvents. Toluene and
dimethylformamide (DMF)
were found to be effective
solvents for both the aldol re-
action and hydrogenation, af-
fording the corresponding al-
kylated product. Although a
high yield of the a,b-unsatu-
rated nitrile was obtained
using ethanol as a solvent,
the reaction rate for hydroge-
nation was slightly low. A
nonpolar solvent, n-heptane,
was found to be ineffective
for the aldol reaction.
Entry
Carbonyl compound
CH2O
Time of (ii) [h]
Product
Isolated yield [%]
1[b,c]
2
1
1
1
91[d]
81
3
92
4
1
99[d]
98[d]
19[d,e]
88
5
2
6
24
3
7
In addition to the benzal-
dehyde derivatives, a-alkyl-
ACHTREUNGations of 1b with linear and
8[f]
9[g]
1
66
6.5
92
branched aliphatic aldehydes
occurred smoothly (Table 9,
entries 1–4). Formaldehyde is
an important electrophilic re-
agent in the C1 chemistry. a-
Alkylation effectively pro-
ceeded even in the presence
of water: a 91% yield of 2-
cyanopropionic acid ethyl
10[g]
–
trace[h]
[a] Reaction conditions; i) nitrile (1 mmol), carbonyl compounds (1 mmol), Pdnano/HT (0.1 g; Pd: 0.01 mml),
toluene (3 mL), 2 h, 808C, Ar. ii) 608C, H2 (1 atm). [b] DMF (3 mL) was used as solvent. [c] 37% aqueous
HCHO was used, 3 h for aldol reaction. [d] Determined by GC using an internal standard. [e] 80% of the un-
saturated nitrile was obtained. [f] At 1008C for aldol reaction. [g] Malononitrile (1 mmol) was used instead of
ethyl cyanoacetate. [h] Aldol reaction scarcely occurred.
ester was obtained from ethyl cyanoacetate with a commer-
cial aqueous 37% solution of formaldehyde, a convenient
be an ideal catalyst support for efficient reactions of various
polarized organic compounds.
formaldehyde source (Ta
with 2-thiophenaldehyde took place readily, but hydrogena-
ble 9, entry 1).[29] The aldol reaction
ACHTREUNG
A
N
One-pot synthesis of a,a-dialkylated nitriles: As the Ru/HT
and Pdnano/HT possess catalytically active metal and base
sites, the applicability of hydrotalcite-supported metals (M/
HTs) as multifunctional catalysts is highlighted by their abil-
ity to catalyze consecutive transformations of a-alkylated ni-
triles in a single reactor. Here, we attempted a one-pot syn-
thesis of glutaronitrile derivatives by Michael reaction of a-
alkylated nitriles with electron-deficient olefins on the base
sites of the HT [Eq. (5); ii)] after the M/HT-catalyzed a-al-
kylation [Eq. (5); i)].
tion of the unsaturated nitrile occurred to only slight extent
under the present reaction conditions owing to strong coor-
dination of the sulfur atom to the Pd species (Table 9,
entry 6). To extend the scope of carbonyl substrates, the use
of ketones was also examined: ethyl cyanoacetate and malo-
nonitrile reacted with cyclohexanone, affording good to ex-
cellent yields of the corresponding products (Table 9, en-
tries 8 and 9), but the aldol reaction with acetophenone
barely occurred (Table 9, entry 10).
After the reaction of 1b with 4, the used Pdnano/HT cata-
lyst was easily recovered from the reaction mixture by
simple filtration, and ICP analysis of the filtrate confirmed
that the Pd content was below the detection limit
(0.03 ppm). The recovered Pdnano/HT catalyst was found to
be recyclable with retention of its high catalytic activity and
selectivity; the first, second, and third runs afforded 95, 93,
and 93% yield of the product, respectively.
The IR spectra of both the HT and Pdnano/HT, upon treat-
ment with 5, revealed a shift of the n(CN) band toward
2147 cmÀ1 in comparison with the free cyano group at
2224 cmÀ1. This suggests that the large positive electric po-
tential of the HT surface induces a high concentration of ni-
trile compounds close to the surface,[30] enhancing hydroge-
nation and aldol reaction rates. It seems that the HT would
Table 10 shows the results of consecutive a-alkylation/Mi-
chael reaction for various substrates using Pdnano/HT and
Ru/HT. For example, after the a-alkylation of 1b with 4
using the Pdnano/HT catalyst, acrylonitrile was added to the
same flask and further reaction under an Ar atmosphere af-
forded 2-benzyl-2-carboethyoxyglutaronitrile in 94% overall
yield (Table 10, entry 1). The Pdnano/HT catalyst also pro-
moted successive reaction using methyl acrylate, n-butyl
Chem. Eur. J. 2006, 12, 8228 – 8239
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8235

K. Kaneda et al.
Table 10. One-pot a,a-dialkylation of nitriles using the M/HTs.[a]
AHCTREUNG
Entry Nitrile
Aldehyde or Alcohol Olefin
Method Product
Isolated yield [%][b]
94
1
1b
1b
1b
4
A
2
4
4
A
A
98
79
3[c]
4[d]
1b
1b
4
A
79
Experimental Section
5[e]
6[f]
7
HCHO
EtOH
EtOH
EtOH
A
B
B
B
63
General: 1H and 13C NMR spectra
were obtained on JEOL GSX-270 or
JNM-AL400 spectrometers at 270 or
400 MHz in CDCl3 with TMS as an
internal standard. Infrared spectra
were obtained with a JASCO FTIR-
410. Analytical GLC and GLC-mass
93[g]
80
8
84[g]
were performed using
a Shimadzu
GC-8 A PF with flame ionization de-
tector equipped with KOCL 3000T,
Silicon SE-30, and OV-17 columns,
[a] Reaction conditions; Method A: i) nitrile (1 mmol), carbonyl compounds (1 mmol), Pdnano/HT (0.1 g; Pd:
0.01 mml), toluene (3 mL), 2 h, 808C, Ar. After the completion of aldol reaction, the reaction mixture was fur-
ther treated at 608C for 1 h under H2 (1 atm). ii) Olefin (1.5 mmol), 5 h, 708C, Ar. Method B: i) nitrile
(1 mmol), alcohol (2 mL), Ru/HT (0.15 g: 0.0075 mmol), 1808C, 20 h, Ar. ii) Olefin (3 mmol), DMSO (2 mL),
1508C, 1 h, Ar. [b] Overall yield based on nitrile. [c] At 1108C, 12 h for Michael reaction. [d] A solution of
methyl vinyl ketone (1.5 mmol) in toluene (2 mL) was slowly added over 6 h and further reacted for 4 h.
[e] DMF (3 mL) was used as solvent. [f] DMF (3 mL) was used as solvent for Michael reaction. [g] Deter-
mined by GC by an internal standard.
and
a Shimadzu GCMS QP5000
equipped with ULBON HR-1 col-
umns. A JEOL JMS-700 mass spec-
trometer was used for HRMS analy-
ses. Powder X-ray diffraction patterns
were recorded using Philips X’Pert-
MPD with CuKa radiation. XPS were
measured on Shimadzu ESCA-KM
using MgKa radiation. Inductively coupled plasma measurement was per-
formed using a Nippon Jarrell-Ash ICAP-575 Mark II. Ru and Pd K-
edge X-ray absorption spectra were recorded at the beam line 01B1 sta-
acrylate, and methyl vinyl ketone (Table 10, entries 2–4).
The Ru/HT-catalyzed a-ethylation of phenylacetonitrile pro-
ceeded smoothly, followed by Michael reaction with acrylo-
nitrile to give 2-ethyl-2-phenylglutaronitrile in 93% overall
yield (Table 10, entry 6), while the traditional method using
iodoethane and Triton B afforded only a 39% yield of the
above product.[1b] Methyl acrylate and acrylamide were also
found to be good acceptors (Table 10, entries 7 and 8). It
can be said that a,a-dialkylation of nitriles using the M/HT
catalysts is a powerful protocol for one-pot synthesis of
highly substituted glutaronitrile derivatives. Unfortunately,
a,b-disubstituted olefins, such as crotononitrile and 2-cyclo-
hexen-1-one, were less active under these reaction condi-
tions.
tion attached to the SiACHTRE(UNG 311) monochromator at SPring-8 for JASRI,
Harima, Japan (2004 A0489-NXa-np and 2005 A0296-NXa-np). Fluores-
cence yield was collected at room temperature. Data analyses were per-
formed with the FACOM M-780 computer system of the Data Processing
Center of Kyoto University and the “REX2000 ver. 2.3” program
(RIGAKU). The detailed procedures for data analysis are described else-
where.[31] The inverse FTs and curve-fitting results of the Ru/HT and Pd/
HTs are shown as Figures 7 and 8, respectively.
A hydrotalcite (HT), Mg6Al2(OH)16CO3, was obtained from TOMITA
Pharmaceutical Co. Ltd., Japan. MgO, Mg(OH)2, and Al(OH)3 were pur-
chased from Wako Pure Chemicals. g-Al2O3 (JRC-ALO-4) was also used.
RuCl3·nH2O, PdCl2, and supported Pd catalysts (Pd/carbon, Pd/Al2O3,
Pd/SiO2, Pd/TiO2) were obtained from N. E. Chemcat and Wako Pure
Chemical. Nitriles, alcohols, carbonyl compounds, and solvents were pur-
chased from Wako, Tokyo Kasei, and Aldrich, and purified by the stand-
Conclusion
Hydrotalcite-supported ruthe-
nium and palladium com-
pounds have been developed
and explored as highly active
multifunctional catalysts for
novel environmentally friendly
a-alkylation of various nitriles
with alcohols and carbonyl
compounds. These catalysts are
reusable and applicable to one-
pot a,a-dialkylation for synthe-
Figure 7. The inverse FTs of the Ru/HT performed in the 0.9–2.0 (A) and 1.9–3.0 Š (B) ranges. The dotted
sis of glutaronitrile derivatives.
One-pot syntheses using het-
À
À
À
lines in (A) and (B) showthe results of curve-fitting analysis using five Ru O (A), and one Ru O, and Ru
Mg (B) shell parameters.
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Chem. Eur. J. 2006, 12, 8228 – 8239

a-Alkylated Nitriles
FULL PAPER
catalyst was separated by filtration and
the GC analysis of the filtrate showed a
98% yield of (Z)-2-phenylcinnamoni-
trile. The Ru/HT also promotes this
condensation to afford (Z)-2-phenylcin-
namonitrile in 96% yield.
a-Alkylation using deuterated benzyl
alcohol: The Ru/HT (0.15 g, Ru:
0.15 mmol), toluene (2 mL), benzyl-
[D7]-alcohol (1.5 mmol), and phenylace-
tonitrile (1.0 mmol) were placed in a
pyrex pressure tube (15 mL). The reac-
tion mixture was vigorously stirred at
1808C under Ar. After 20 h, the catalyst
was separated by filtration, and the 1H
NMR analysis of the filtrate showed the
formation of deuterated a-alkylated
products, 2-[D]-2-phenyl-3-[D]-3-[D5]-
phenylpropionitrile and 2-phenyl-3-
Figure 8. The inverse FTs of A) PdII/HT and B) Pdnano/HT performed in the 1.2–2.0 Š (A) and 2.0–2.9 Š (B)
À
À
ranges. The dotted lines showthe results of curve-fitting analysis using A) four Pd O, and B) Pd Pd shell
parameters.
ard procedures prior to experiments. The identities of products were con-
[D2]-3-[D5]-phenylpropionitrile, in a ratio of 3:4.
firmed by comparison with reported mass and NMR data. All new prod-
ucts were characterized by 1H and 13C NMR spectra, infrared spectra,
mass spectra, and HRMS analysis.
A typical example of the Pdnano/HT-catalyzed a-alkylation of nitrileswith
alcohols: Ethyl cyanoacetate (1 mmol), benzaldehyde (1 mmol), the
Pdnano/HT (0.1 g, Pd: 0.01 mmol), and toluene (3 mL) were added into a
glass reactor. After the aldol reaction (808C, 2 h) and the hydrogenation
(608C, 1 h), the catalyst was filtered out and GC analysis of the filtrate
showed a 98% yield of ethyl-2-cyano-3-phenylpropanoate. The filtrate
was evaporated and the crude product was purified by column chroma-
tography using silica (hexane/ethyl acetate = 9:1) to afford a pure prod-
uct (94% isolated yield).
3-(4-Aminophenyl)-2-phenylpropionitrile: 1H NMR (400 MHz, CDCl3):
d = 3.05 (m, 2H), 3.62 (br, 2H), 3.92 (dd, J = 6.8, 8.0 Hz, 1H), 6.59 (d,
J = 8.4 Hz, 2H), 6.90 (d, J = 8.4 Hz, 2H), 7.23–7.37 ppm (m, 5H); 13C
{1H} NMR (100.4 MHz, CDCl3): d = 40.2, 41.6, 115.1, 120.5, 126.1, 127.5,
128.0, 128.8, 130.1, 135.4, 145.5 ppm; IR (KBr): n˜max = 3400, 3336, 3056,
3030, 2931, 2849, 2315, 2246, 1868, 1683, 1653, 1633, 1558, 1541, 1515,
1457, 1338, 1272, 1177, 835, 791, 744, 694, 576, 509 cmÀ1; MS (EI): m/z
(%): 211 [M+ÀH], 193, 176, 165, 139, 128, 116, 106 (100), 89, 77, 63, 51;
HRMS calcd for C15H14N2: 222.1157; found: 222.1175.
Preparation of the Ru-grafted hydrotalcite: The HT, Mg6Al2(OH)16CO3
(1.0 g), was added to an aqueous solution of RuCl3·nH2O (5.0”10À4 m,
100 mL). The resulting heterogeneous mixture was stirred at 258C for 1 h
under air. The solid product was separated by centrifugation, washed
thoroughly with deionized water, and dried in vacuo at room tempera-
ture, affording Ru/HT as a gray powder (Ru content: 0.5 wt%). X-ray
diffraction studies showed the retention of a layered structure with a
basal spacing of 7.7 Š. Various ruthenium-supported solid base catalysts,
such as Ru/MgO, Ru/Al2O3, Ru/Mg(OH)2, and Ru/Al(OH)3 were synthe-
sized by the same procedure.
Preparation of the hydrotalcite-supported Pd nanoparticles: The HT,
Mg6Al2(OH)16CO3, (1.0 g) was added to an aqueous solution of PdCl2
(100 mL, 0.1 mmol) containing KCl (0.1 g). The heterogeneous mixture
was stirred at 258C for 1 h under air to afford a pale yellowpowder and
was then successively reduced in the presence of H2 (1 atm) at 1008C for
8 h. The solid product was separated by centrifugation, washed thorough-
Procedure for the large-scale a-alkylation of ethyl cyanoacetate with
benzaldehyde: Ethyl cyanoacetate (1.70 g, 15 mmol), benzaldehyde
(1.59 g, 15 mmol), the Pdnano/HT (0.1 wt%, 0.60 g, Pd: 0.006 mmol), and
toluene (20 mL) were added into a glass reactor. After the aldol reaction
(808C, 3 h) and the hydrogenation (808C, 20 h), the catalyst was filtered
out and GC analysis of the filtrate showed a 97% yield of ethyl-2-cyano-
3-phenylpropanoate. The filtrate was evaporated and the crude product
was purified by distillation (1808C/5.0 mmHg) to afford pure product
(2.9 g, 95% yield, TON = 2380).
ly with deionized water, and dried at 1108C for 12 h, affording the Pdnano
/
HT as a black powder (Pd content: 1.0 wt%). Pd/MgO was prepared by
the same procedure.
A typical example for the Ru/HT-catalyzed a-alkylation of nitrileswith
alcohols: The Ru/HT (0.15 g, Ru: 0.0075 mmol), ethanol (2 mL), and
phenylacetonitrile (1.0 mmol) were placed in
a pyrex pressure tube
(15 mL). The resulting mixture was vigorously stirred at 1808C under Ar.
After 20 h, the catalyst was separated by filtration and the GC analysis of
the filtrate showed a 98% yield of 2-phenylbutyronitrile. The filtrate was
evaporated and the crude product was purified by column chromatogra-
phy using silica (hexane/ethyl acetate 9:1) to afford a pure product
(0.136 g, 94% isolated yield).
Synthesis of a,a-dialkyl phenylacetonitrilesusing the Pd nano/HT: Ethyl cy-
anoacetate (1 mmol), benzaldehyde (1 mmol), the Pdnano/HT (0.1 g, Pd:
0.01 mmol), and toluene (3 mL) were added into a glass reactor. After
the aldol reaction (808C, 2 h) and the hydrogenation (608C, 1 h), acrylo-
nitrile (1.5 mmol) was added to the same flask and further reacted at
708C under an Ar atmosphere. After 5 h, the catalyst was filtered out.
The filtrate was evaporated and the crude product was purified by
column chromatography using silica to afford pure 2-carboethoxy-2-
benzyl glutaronitrile (94% yield).
2-Benzyl-2-carboethoxyglutaronitrile: 1H NMR (400 MHz, CDCl3): d =
1.21 (t, J = 7.0 Hz, 3H), 2.10–2.18 (m, 1H), 2.39–2.52 (m, 2H), 2.57–2.65
(m, 1H), 3.17 (dd, J = 13.4, 56.4 Hz, 2H), 4.21 (q, J = 7.2 Hz, 2H),
7.24–7.36 ppm (m, 5H); 13C{1H} NMR (100.4 MHz, CDCl3): d = 13.8,
14.0, 32.1, 43.2, 50.2, 63.4, 117.28, 117.29, 128.2, 128.7, 129.8, 132.8,
167.0 ppm; IR (KBr): n˜max = 3033, 2981, 2938, 2250, 1742, 1673, 1641,
1497, 1455, 1371, 1231, 1091, 1014, 857, 773, 743, 702 cmÀ1; MS (EI): m/z
(%): 256 [M+], 227, 211, 200, 183, 158, 142, 131, 115, 91 (100), 78, 65, 51;
HRMS calcd for C15H16N2O2: 256.1212; found: 256.1222.
Procedure for the large-scale a-alkylation of phenylacetonitrile with
ethanol: The Ru/HT (0.8 g, Ru: 0.04 mmol), ethanol (5 mL), and phenyl-
acetonitrile (20 mmol) were placed in a pyrex pressure tube (15 mL). The
reaction mixture was vigorously stirred at 1808C under Ar for 30 h. The
catalyst was then separated by filtration and the GC analysis of the fil-
trate showed an 82% yield of 2-phenylbutyronitrile.
Hydrogen-transfer reaction of benzyl alcohol with 2-phenylcinnamoni-
trile: The Ru/HT (0.15 g, Ru: 0.0075 mmol), toluene (2 mL), benzyl alco-
hol (1.5 mmol), and (Z)-2-phenylcinnamonitrile (1.0 mmol) were placed
in a pyrex pressure tube (15 mL). The reaction mixture was vigorously
stirred at 1808C under Ar. After 20 h, the catalyst was separated by fil-
tration and the GC analysis of the filtrate showed a 98% yield of 2,3-di-
phenylpropionitrile together with benzaldehyde.
Aldol condensation of phenylacetonitrile with benzaldehyde: The parent
HT (0.15 g), toluene (2 mL), benzaldehyde (1.5 mmol), and phenylaceto-
nitrile (1.0 mmol) were placed in a pyrex pressure tube (15 mL). The re-
action mixture was vigorously stirred at 1808C under Ar. After 7 h, the
4-Carboethoxy-4-cyano-5-phenylpentanioc acid methyl ester: 1H NMR
(400 MHz, CDCl3): d = 1.17 (t, J = 7.0 Hz, 3H), 2.15–2.23 (m, 1H),
2.33–2.46 (m, 2H), 2.57–2.65 (m, 1H), 3.15 (dd, J = 13.6, 52.8 Hz, 2H),
Chem. Eur. J. 2006, 12, 8228 – 8239
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8237

K. Kaneda et al.
3.69 (s, 3H), 4.15 (q, J = 7.2 Hz, 2H), 7.25–7.34 ppm (m, 5H); 13C{1H}
NMR (100.4 MHz, CDCl3): d = 13.9, 30.1, 32.0, 43.2, 50.5, 51.9, 62.9,
118.1, 127.8, 128.5, 129.8, 133.6, 167.7, 171.7 ppm; IR (KBr): n˜max = 2985,
2955, 2246, 1740, 1499, 1448, 1381, 1227, 1203, 1091, 1016, 857, 773, 745,
702 cmÀ1; MS (EI): m/z (%): 289 [M+], 258, 212, 202, 184, 174, 155, 142,
129, 115, 91 (100), 77; HRMS calcd for C16H19NO4: 289.1314; found:
289.1299.
4-Carboethoxy-4-cyano-5-phenylpentanoic acid n-butyl ester: 1H NMR
(270 MHz, CDCl3): d = 0.93 (t, J = 7.4 Hz, 3H), 1.17 (t, J = 7.1 Hz,
3H), 1.30–1.44 (m, 2H), 1.55–1.66 (m, 2H), 2.14–2.65 (m, 4H), 3.15 (dd,
J = 13.5, 37.2 Hz, 2H), 4.12 (m, 4H), 7.25–7.34 ppm (m, 5H); 13C{1H}
NMR (67.8 MHz, CDCl3): d = 13.6, 13.9, 19.1, 30.3, 30.5, 32.0, 43.1, 50.5,
62.8, 64.7, 118.1, 127.8, 128.4, 129.7, 133.6, 167.7, 171.2 ppm; IR (KBr):
n˜max = 3033, 2964, 2939, 2874, 2246, 1736, 1498, 1455, 1397, 1371, 1292,
1229, 1186, 1089, 1065, 1018, 964, 945, 857, 771, 743, 701 cmÀ1; MS (EI):
m/z (%): 331 [M+], 302, 285, 272, 258, 243, 230, 212, 202, 184, 174, 155,
142, 129, 115, 103, 91 (100), 74, 55; HRMS calcd for C19H25NO4:
331.1784; found: 331.1810.
yield of 2-ethyl-2-phenylglutarodinitrile based on phenylacetonitrile. For
the reactions of methyl acrylate and acryl amide as Michael acceptors,
the solvent used was DMSO instead of DMF.
4-Cyano-4-phenylhexanoic acid methyl ester: 1H NMR (400 MHz,
CDCl3): d = 0.85 (t, J = 7.4 Hz, 3H), 1.85–2.44 (m, 6H), 3.54 (s, 3H),
7.22–7.37 ppm (m, 5H); 13C {1H} NMR (100.4 MHz, CDCl3): d = 9.6,
30.2, 34.3, 35.4, 48.4, 51.7, 121.5, 125.9, 127.9, 128.9, 137.0, 172.5 ppm; IR
(KBr): n˜max = 2974, 2880, 2236, 1738, 1493, 1448, 1438, 1375, 1337, 1296,
1257, 1201, 1173, 1030, 1011, 899, 882, 762, 700, 624, 517 cmÀ1; MS (EI):
m/z (%): 231 [M+], 216, 204, 200, 189, 170, 157, 142 (100), 129, 115, 103,
91, 77; HRMS calcd for C14H17NO2: 231.1259; found: 231.1282.
1
4-Cyano-4-phenylhexanoic acid amide: H NMR (400 MHz, CDCl3): d =
0.91 (t, J = 7.4 Hz, 3H), 1.93–2.08 (m, 3H), 2.18–2.43 (m, 3H), 5.25–5.88
(br, 2H), 7.28–7.39 ppm (m, 5H); 13C {1H} NMR (100.4 MHz, CDCl3): d
= 10.4, 32.2, 35.2, 36.2, 49.2, 122.5, 126.6, 128.6, 129.6, 137.8, 174.2 ppm;
IR (KBr): n˜max = 3433, 3201, 2974, 2935, 2236, 1669, 1455, 1416, 1025,
762, 700, 584, 519 cmÀ1; MS (EI): m/z (%): 216 [M+], 199, 187, 170, 158,
144, 129, 115, 103, 91, 77, 73, 59 (100), 44; HRMS calcd for C13H16N2O:
216.1263; found: 216.1275.
4-Carboethoxy-4-cyano-5-phenyl-2-hexanone: 1H NMR (400 MHz,
CDCl3): d = 1.17 (t, J = 7.2 Hz, 3H), 2.08–2.76 (m, 4H), 2.16 (s, 3H),
IR measurements: After treatment of the HT, Ru/HT, and Pdnano/HT
with substrates in toluene, the solid catalysts were filtered, dried under
an atmospheric pressure, and made into a disk with KBr. All manipula-
3.14 (dd, J
= 13.4 , 54.6 Hz, 2H), 4.15 (q, J = 7.2 Hz, 2H), 7.23–
7.34 ppm (m, 5H); 13C{1H} NMR (100.4 MHz, CDCl3): d = 13.9, 29.9,
30.7, 39.2, 43.2, 50.5, 62.8, 118.4, 127.8, 128.4, 129.8, 133.7, 167.9,
205.3 ppm; IR (KBr): n˜max = 3064, 3034, 2983, 2936, 2245, 1957, 1887,
1739, 1676, 1644, 1543, 1496, 1448, 1367, 1223, 1167, 1094, 1022, 961, 917,
859, 775, 743, 702, 618, 571, 481 cmÀ; MS (EI): m/z (%): 273 [M+], 255,
244, 228, 216, 203, 182, 174, 158, 142, 130, 115, 103, 91 (100), 71, 78, 65,
43; HRMS calcd for C16H19NO3: 273.1365; found: 273.1383.
À
tions for the measurement of Ru H species were carried out under an
Ar atmosphere. Figure 9 shows the IR spectra of both the HT and Pdnano
/
HT upon treatment with 5.
Synthesis of a,a-dialkyl phenylacetonitrilesusing the Ru/HT : The Ru/HT
(0.15 g, Ru: 0.0075 mmol), ethanol (2 mL), and phenylacetonitrile
(1.0 mmol) were placed into a pyrex pressure tube (15 mL). The reaction
mixture was vigorously stirred at 1808C under Ar for 20 h. After comple-
tion of the alkylation, excess ethanol was evaporated. Acrylonitrile
(3.0 mmol) and DMF (2 mL) were then added to the same pressure tube
and further reaction occurred at 1508C. After 1 h, the catalyst was sepa-
rated by filtration, and the GC analysis of the filtrate showed a 93%
Acknowledgements
This investigation was supported by a Grant-in-Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Science, and
Technology of Japan (16206078). We thank Dr. Tomoya Uruga and Dr.
Hajime Tanida (JASRI) for XAFS measurements and the Center of Ex-
cellence (21COE; program “Creation of Integrated Ecochemistry”,
Osaka University). TEM measurements were conducted at the Research
Center for Ultrahigh-Voltage Electron Microscopy at Osaka University.
We are also grateful to the Department of Materials Engineering Sci-
ence, Graduate School of Engineering Science, Osaka University, for sci-
entific support with the gas-hydrate analyzing system (GHAS). K. M.
thanks the JSPS Research Fellowships for Young Scientists.
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8238
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Chem. Eur. J. 2006, 12, 8228 – 8239

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Received: March 7, 2006
Published online: August 9, 2006
Chem. Eur. J. 2006, 12, 8228 – 8239
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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