A bifunctional PdVMgO solid catalyst for the one-pot selective N-monoalkylation of amines with alcohols

Article abstract of DOI:10.1002/chem.200901501

It has been found that a bifunctional metal Pd/base (MgO) catalyst performs the selective monoalkylation of amines with alcohols. The reaction goes through a series of consecutive steps in a cascade mode that involves: 1) the abstraction of hydrogen from the alcohol that produces the metal hydride and the carbonyl compound; 2) condensation of the carbonyl with the amine to give an imine, and 3) hydrogenation of the imine with the surface hydrogen atoms from the metal hydride. Based on isotopic and spectroscopic studies and on the rate of each elementary step, a global reaction mechanism has been proposed. The controlling step of the process is the hydride transfer from the metal to the imine. By changing the crystallite size of the Pd, it is demonstrated that this is a structure-sensitive reaction, whereas the competing processes that lead to subproducts are not. On these bases, a highly selective catalyst has been obtained with Pd crystallite size below 2.5 nm in diameter. The high efficiency of the catalytic system has allowed us to extend the process to the one-pot synthesis of piperazines.

Full text of DOI:10.1002/chem.200901501

DOI: 10.1002/chem.200901501
A Bifunctional Pd/MgO Solid Catalyst for the One-Pot Selective
N-Monoalkylation of Amines with Alcohols
Avelino Corma,* Tania Rꢀdenas, and Marꢁa J. Sabater*[a]
Abstract: It has been found that a bi-
surface hydrogen atoms from the metal
hydride. Based on isotopic and spectro-
scopic studies and on the rate of each
imine. By changing the crystallite size
functional metal Pd/base (MgO) cata-
lyst performs the selective monoalkyla-
tion of amines with alcohols. The reac-
tion goes through a series of consecu-
tive steps in a cascade mode that in-
volves: 1) the abstraction of hydrogen
from the alcohol that produces the
metal hydride and the carbonyl com-
pound; 2) condensation of the carbonyl
with the amine to give an imine, and
3) hydrogenation of the imine with the
of the Pd, it is demonstrated that this is
a structure-sensitive reaction, whereas
the competing processes that lead to
subproducts are not. On these bases, a
highly selective catalyst has been ob-
tained with Pd crystallite size below
2.5 nm in diameter. The high efficiency
of the catalytic system has allowed us
to extend the process to the one-pot
synthesis of piperazines.
elementary step,
a global reaction
mechanism has been proposed. The
controlling step of the process is the
hydride transfer from the metal to the
Keywords: heterogeneous catalysis ·
hydrogen transfer
·
magnesium
oxide · monoalkylation · palladium
Introduction
of amines through a series of consecutive reactions in a cas-
cade mode with high selectivity. The process involves the ab-
straction of hydrogen from the alcohol that produces the
metal hydride and the carbonyl compound from the alcohol.
The carbonyl compound condenses with the amine to give
an imine, which is hydrogenated to a final monoalkylated
amine with the surface hydrogen atoms from the metal hy-
drides.
We show that this system can be applied to build organic
molecules of industrial interest such as piperazines,[4,5] which
are used as building blocks in medicine through the step-by-
step introduction of different pharmacophoric moieties. It is
worth noting that at present piperazines are synthesized by
the reduction of the corresponding (di)ketopiperazines or by
various cyclization reactions, for example, by dialkylation of
amines with bis(2-chloroethyl)amine, by intramolecular re-
ductive coupling of diamines,[6–9] or the recent alkylation of
diamines with alcohols mediated by iridium and rutheni-
um.[2,3]
Monoalkylation of amines with alcohols is a reaction that
produces C N bonds yielding substituted amines. It has
[1]
À
been reported that RuII and IrI complexes are able to cata-
lyze the direct alkylation of amines and sulfonamides by al-
cohols under transfer hydrogenation conditions.[2,3a–f] How-
ever, these reactions usually require an excess of a soluble
base and the valuable catalysts are difficult to recover.
Despite the fundamental and practical interest of the re-
action, there is only one precedent of a heterogeneous cata-
lyst (Raney Ni) able to perform the monoalkylation of
amines working with an excess of alcohol (3 g) and a large
amount of catalyst. The global reaction mechanism was un-
known, although the formation of radical intermediates was
considered to be involved.
We will show here that, by using a Pd on MgO bifunction-
al solid catalyst, it is possible to catalyze the monoalkylation
In this work, a series of bifunctional catalysts based on
metals with different abilities to form hydrides and to give
back the hydrogen—that is, Pd, Pt, and Au—have been sup-
ported on MgO.[10] Among them, Pd/MgO is able to perform
the N-monoalkylation of amines with high selectivity and
with a turnover frequency (TOF) about four times higher
than that of the homogeneous Ru or Ir catalysts[3d] working
under similar reaction conditions.
[a] Prof. A. Corma, T. Rꢀdenas, Dr. M. J. Sabater
Instituto de Tecnologꢁa Quꢁmica UPV-CSIC
Avda. Los Naranjos s/n, 46022 Valencia (Spain)
Fax : (+34)963877809
E-mail: mjsabate@itq.upv.es
acorma@itq.upv.es
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200901501.
254
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 254 – 260

FULL PAPER
Mechanistic studies show that the controlling step of the
global process is the hydride transfer from the metal to the
imine, and that this is a structure-sensitive reaction. There-
fore a metal catalyst prepared within the form of small crys-
tallites that can easily take and give back hydride ions gives
the best performance for this reaction. We have seen that
the solid catalyst maintains activity and selectivity after
being reused twice.
In a first approximation, the formation of products 1 and
2 can be explained by means of oxidative removal of hydro-
gen from benzylic alcohol to a afford benzaldehyde (de-
tected only when aniline is not present) and a characteristic
metal monohydride and/or dihydride.[11] The aldehyde reacts
with aniline to give the condensation product 1, which is hy-
drogenated by the palladium hydride to afford the new
monoalkylated amine 2. A control experiment shows that in
the absence of the basic solid support MgO, Pd (Pd/C) can
still catalyze the reaction, albeit affording much lower yield
and selectivity of product 2 (see entry 2 in Table 1). It has
also to be noticed that benzaldehyde and aniline react in the
absence of catalyst, though at much lower reaction rate,
thus making the polymerization of aniline more competitive
and resulting in a decreased yield of 2.
Pd/MgO is still highly selective toward the N-monoalky-
lated amine 2, even when using equimolar amounts of the
amine and the alcohol under milder conditions (1108C;
entry 4, Table 1). Moreover, the solid can be recovered and
reused up to three times with only a slight loss of activity
upon recycling. Nonetheless, the selectivity and yields of
products can be kept by extending the reaction time
(entry 3, Table 1).
Results and Discussion
For proving the concept we have used the reaction between
benzylic alcohol and aniline. Thus, when benzylic alcohol
was allowed to react with aniline in trifluorotoluene at
1808C with Pd/MgO as catalyst, the products obtained were
the imine 1 and the amine 2. These products account for
92% of the converted material, with the rest of the products
being toluene and benzene (see Scheme 1 and entry 1 in
Table 1).
When Pd is supported on two other basic supports, that is,
Al–Mg hydrotalcite (HT) and hydroxyapatite (HAP), the
resulting catalysts are active but the yield and selectivity to
2, and even to 1+2, are lower than in the case of MgO (see
entries 5 and 6 in Table 1). As far as the metal is concerned,
we chose two additional metals (Pt and Au) and their activi-
ty was compared with Pd. It is known that gold has a low
tendency to form hydrides and they are quite unstable.[12–14]
In clear contrast, Pt has an ample precedent in the literature
for forming hydride complexes with a very strong metal–hy-
drogen bond.[15,16] Thus, gold and platinum were supported
on MgO (for details on the preparation, see the Experimen-
tal Section) and their perfor-
Scheme 1. Product distribution obtained in the N-alkylation reaction of
aniline with benzyl alcohol catalyzed by Pd/MgO (0.8% Pd) at 1808C.
mance as catalysts for the
Table 1. N-Alkylation of anilines with benzyl alcohol catalyzed with diverse bifunctional solid catalysts.[a]
monoalkylation of aniline was
studied and compared with
that of palladium (Figure 1).
With Pd/MgO as catalyst, we
noticed a slight reduction in
the yield of amine 2, which
became rapidly stabilized in a
steady state with time (see
Figure 1, bottom). We inter-
preted this result by assuming
that the reverse reaction, that
is, dehydrogenation from 2 to
afford the imine 1, occurs si-
multaneously, so that both
compounds interconvert one to
another until reaching an equi-
librium concentration.[17]
Entry
Catalyst
C [%][b]
Yield [%][c]
benzene toluene
t [h]
TON[d]
1
2
1
2
Pd/MgO (0.8%)
Pd/C (5%)
99
91
96
13
23
12
8
11
39
49
21
7
42
10
16
13
11
79
28
84
80
49
26
38
61
59
36
80
47
38
30
traces
3
0
7
16
0
0.25
2.3
6
0.8
2
2
5
1
2
192
198
3[f]
4[g]
5
Pd/MgO (0.8%)
Pd/MgO (0.8%)
Pd/HT (0.55%)
Pd/HAP (0.55%)
Au/MgO (1.0%)
Pt/MgO (1.0%)
AuPd/MgO
AuPt/MgO
PdPt/MgO
Pd/MgO (2.0%)
Pd/MgO (5.0%)
Pd/MgO (10.0%)
97[e]
172
90
traces
1
100
100
93
98
76
87
100
84
75
66
5
3
3
6
2
8
3
6
8
9
34
31
2
11
7
2
7
16
15
16
182
167
156
145
6
7
8
9[h]
10[i]
11[i]
12
13
14
123[e]
149[e]
148[e]
561
2
0.75
0.75
1
521
408
1
[a] Reaction conditions: benzyl alcohol (1 mmol), aniline (3 mmol), n-dodecane (0.1 mmol), catalyst
(0.0075 mmol Pd, Pt, or Au), trifluorotoluene (1 mL), T=1808C. [b] Conversions were determined by GC on
the basis of benzyl alcohol consumption. [c] Determined by GC. [d] Turnover number calculated as mmol of
converted alcohol/mmol of catalyst (total Pd content). [e] Turnover number calculated as mmol of converted
alcohol/mmol of surface Pd atoms. [f] After two uses. [g] Reaction conditions: benzyl alcohol (1 mmol), aniline
(1 mmol), n-dodecane (0.1 mmol), catalyst (0.025 mmol Pd), trifluorotoluene (1 mL), T=1108C.
[h] 0.0075 mmol Pd. [i] 0.0075 mmol Pt.
With gold as catalyst, benzyl
alcohol afforded reasonable
yields of benzaldehyde, which
Chem. Eur. J. 2010, 16, 254 – 260
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
255

A. Corma, T. Rꢀdenas, and M. J. Sabater
Scheme 2. Initial reaction rates (r) calculated for the sequential transfor-
mation between benzyl alcohol and aniline catalyzed by Pd/MgO (0.8%
Pd) at 1808C.
Influence of metal crystallite size on reactivity: Since the re-
action-controlling step is the hydrogenation of the imine by
the surface hydrides and hydrogenations are in many cases
structure-sensitive reactions, we have studied the influence
of the Pd crystallite size on the initial rate of formation of
product 2. To do this, a series of Pd/MgO catalysts with dif-
ferent Pd crystallite sizes were prepared (see characteriza-
tion details in Table S1 in the Supporting Information; the
crystallite size distribution measured by TEM is also given
in the Supporting Information, Figure S1). The number of
Pd surface atoms in each sample was calculated by taking
into account the total metal content, crystal-size distribu-
tion, and the calculation procedure given in ref. [19].
When the initial reaction rate per metal surface atom
(turnover frequency, or TOF) is plotted versus the average
crystallite size for Pd (see Figure 2), it can be seen that the
initial reaction rates for the formation of the amine (product
2) as well as the formation of benzaldehyde increase expo-
nentially as the Pd crystallite size decreases.
Figure 1. Comparative plots showing the conversion (C) of benzyl alcohol
against time (top) and the yield of compound 2 versus time in the N-alky-
lation reaction of aniline with benzyl alcohol catalyzed (bottom) by
a) Pd/MgO (0.8%; 0.0075 mmol Pd), b) Pt/MgO (0.75%, 0.0075 mmol),
and c) Au/MgO (1%, 0.0075 mmol).
underwent reaction with aniline to afford compound 1 as
the major product, with the saturated product 2 being
formed in moderate yields (entry 7 in Table 1 and Figure 1).
With platinum supported on MgO, the alcohol was com-
pletely transformed into benzaldehyde and the yields of
amine 2 were higher than those obtained with gold, albeit
lower than with palladium (entry 8 in Table 1 and Figure 1).
The clear superiority of palladium over gold and platinum
for catalyzing this reaction can be explained by taking into
account that the stability of gold and platinum hydrides are
either too low or too high, respectively, and consequently
they are less reactive than palladium hydrides.[12–14,18] This
explanation suggests that the controlling step of the reaction
should be the hydrogenation of the imine through hydrogen
transfer from the metal hydride, and the surface hydride
concentration and its ability to release the hydrogen will de-
termine the activity and selectivity of the catalyst.
Figure 2. Plots showing the initial reaction rates (r0) per surface atom as
a function of metal particle size (d) for a) the hydrogenation transfer re-
action to afford 2; b) dehydrogenation of benzyl alcohol to afford benzal-
dehyde; c) condensation reaction to give 1; d) hydrogenolysis reaction to
give toluene; and e) decarbonylation reaction to afford benzene.
To check the hypothesis, we have measured the initial re-
action rates for each one of the reactions occurring in a se-
quential mode on Pd/MgO (0.8% Pd; see Scheme 2). The
results obtained clearly show that the slowest reaction step
is indeed the hydrogenation of the imine by the surface hy-
drides.
Taking this into account, it is not surprising that the activi-
ty of the metals follows the order Pd>Pt>Au (see en-
tries 1, 7, and 8 in Table 1; and Figure 1). In the case of bi-
metallic catalysts (entries 9–11 in Table 1), the activity is
most probably dominated by Pd.
This result clearly indicates that both reactions (i.e., the
hydride-transfer reaction to the imine as well as dehydro-
genation of the alcohol) are structure-sensitive reactions.[20]
On the other hand, since the initial reaction rate per metal
surface atom remains constant with particle size for the
competing reactions that give toluene and benzene, one can
increase the selectivity to product 2 by preparing catalysts
with smaller Pd crystallite sizes.
256
www.chemeurj.org
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 254 – 260

Bifunctional Pd/MgO Solid Catalyst
FULL PAPER
Reaction mechanism: As already mentioned, the N-alkyla-
tion of amines with alcohols on Pd/MgO occurs through a
series of consecutive reactions in which the first step must
be the abstraction of hydrogen from the alcohol by Pd0 to
give the corresponding carbonyl compound and a divalent
metal hydride. To prove this, we have followed the reaction
using in situ diffuse reflectance (DR) UV/Vis spectroscopy,
and the results given in Figure S2 in the Supporting Infor-
mation show that the freshly prepared Pd/MgO catalyst
gives a spectrum with a broad and structureless band that
has been assigned to Pd0 reduction.[21] The spectrum of the
catalyst recovered after completing the benzylic alcohol
transformation to benzaldehyde (in the absence of amine)
was very similar to that of [PdACHTNUTRGNENG(U acac)2] (acac=acetylaceto-
nate; Figure S2 in the Supporting Information), thus sug-
gesting an initial oxidative addition process from Pd0 to
afford the intermediate Pd2+ mono- or dihydride with the si-
multaneous formation of benzaldehyde. Experiments based
on in situ IR techniques were undertaken to confirm the for-
mation of this palladium hydride bond. In this case, the
course of the reaction was followed from the changes in the
infrared spectrum of Pd/MgO during the cascade reaction,
but the characteristic vibration band of palladium hydride
bonds was not detected by IR spectroscopy.[22] Instead of
this, the IR spectra showed three defined bands at 3480,
3684, and 1325 cmÀ1. The former two bands were assigned
Scheme 3. Incorporation of deuterium in the a-position and/or hydroxyl
group of benzyl alcohol catalyzed by palladium at 1808C, through A) the
monohydride and B) the dihydride mechanism.
If palladium follows path A, no H/D scrambling should
occur and the deuterium would exclusively go back to the
a-C of the alcohol, thereby giving PhCD2OH as the only
product. On the contrary, if path B is operative, then the
deuterium would scramble between carbon and oxygen
(CD/ODꢀ1:1) and two different deuterated alcohols would
be detected at the end (see Scheme 3 and Figure S3).[24]
1
to hydroxyl vibrations of MgOH species, whereas the third
In our case, the H and 13C NMR spectra of the reaction
[23]
À
one was assigned to Mg H. Formation of this magnesium
mixture showed the formation of monodeuterated chemical
À
hydride could be explained by taking into account that mi-
gration of atomic hydrogen over the palladium metal sur-
face to a different phase (the MgO support) can easily take
place. This migration, which is the basis for the “spillover”
phenomenon, has been widely documented, and the same
can be applied for the “reverse spillover” effect (hydrogen
migration from the MgO support to the metal palladium),
since both processes are energetically favorable.[23]
species Ph
G
PhCH2OH, which should arise from a second deuterium ab-
À
straction from Ph
N
porting Information). Since, in addition to this, the CD2
carbon was not detected in the 13C NMR spectrum, we can
propose that with Pd/MgO as catalyst the formation of
metal hydride species proceeds exclusively through path B.
Thus, by taking into account all the above results, we can
propose the following tentative reaction mechanism for the
monoalkylation of amine with alcohols on the Pd/MgO cata-
lysts (see Scheme 4).
After establishing that the process involves the formation
of the hydride and the controlling step of the reaction corre-
sponds to the transfer of hydride to the imine, we have stud-
ied in detail how and what type of hydride species are
formed.
To do this, we have assumed that when the hydride inter-
mediate is formed, the metal hydride should arise either
À
from the a-C H (see Scheme 3, path A) of the hydrogen
À
À
donor or from both the a-C H and the O H of the alcohol
(path B).[24]
For path B, any of the hydrides on the metal may add to
the imine carbon, since the catalyst would not distinguish
between the proton from the OH and the hydride formed
À
from the a-C H to perform the hydrogenation, thus losing
their identity. Therefore, to find out whether path A or B is
operating with Pd/MgO, an experiment was carried out by
putting PhCD2OH into contact with Pd/MgO at 1808C.
After reaching the equilibrium with the formation of benzal-
1
dehyde (after 1.5 h), we searched the H NMR spectrum of
the alcohol to see if H/D scrambling had occurred (Fig-
ure S3 in the Supporting Information).
Scheme 4. Proposed reaction mechanism for the monoalkylation of ani-
line with benzyl alcohol catalyzed by Pd/MgO.
Chem. Eur. J. 2010, 16, 254 – 260
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
257

A. Corma, T. Rꢀdenas, and M. J. Sabater
À
In this mechanism, a palladium dihydride species Pd H2
lar amounts of 1,2-diamines and ethylene glycol derivatives
at 1608C in acetonitrile and good yields of the respective
heterocycles were obtained (see Table S3 in the Supporting
Information). The results collected in Table S3 indicate that,
by following this approach, 1,2-diamines are also amenable
to a cyclocondensation/N-alkylation reaction following a hy-
drogen-transfer route over the Pd/MgO bifunctional cata-
lyst.
(4) is formed upon direct interaction with the alcohol (and/
or through formation of a palladium alkoxylate intermediate
3). The dihydride metal species 4 would react with the unsa-
turated compound 1 formed by condensation of the alde-
hyde with the amine on the basic sites of MgO.
Scope of the reaction: The reaction has been successfully ex-
tended to other alcohols and amines and the results are
given in Table S2 in the Supporting Information.
The aliphatic alcohol 1-octanol reacts more slowly than
Conclusion
the aromatic benzyl alcohol (see entries 1 and
2 in
Table S2), and the yield of the final monoalkylated amine P2
was lower for the aliphatic than for the aromatic alcohol
(entries 1 and 2 in Table S2). Notably, the yield of the mono-
alkylated aniline improved when a double bond was present
at the a,b-position in the allylic alcohol trans-2-hexenol.
However, no transfer hydrogenation occurred for this imine
bond in the presence of the conjugated C=C bond, so that
the reduction of the latter occurred with complete chemose-
lectivity (see entry 3, Table S2).
The yield of N-alkylated aniline improved significantly
when the monoalkylation of aniline was carried out with the
isomer cis-2-hexenol, and again the selective transfer hydro-
genation of the a,b-unsaturated imine intermediate P1 af-
forded the saturated imine P2 (see entry 4, Table S2). As ex-
pected, a strong reduction in the yield of hydrogenated
product P2 was observed when the double bond was sterical-
ly hindered (see entry 5, Table S2 in the Supporting Infor-
mation).
In close connection to this, and just to check if the reactiv-
ity of the C=N bond towards hydrogenation increases when
this functionality is far away from the C=C group, we at-
tempted the monoalkylation of aniline with 5-hexenol. In
this case, a complex mixture of products derived from hy-
drogenation of the C=C bond, the imine, as well as both
multiple bonds was obtained (see entry 6, Table S2 in the
Supporting Information).
From these results it can be concluded that the substitu-
tion and the position of the double bond relative to the C=
N group has a strong influence on the chemoselectivity of
the process. Thus, the C=C double bond is hydrogenated
with difficulty when it is sterically hindered or when it is far
from the C=N group. On the other hand, in conjugated sys-
tems, the activated double bond is exclusively hydrogenated
with preference over the C=N bond.
The Pd/MgO catalyst is able to perform the N-monoalkyla-
tion of amines with high selectivity and a turnover frequen-
cies (TOF), about four times higher than that of homogene-
ous Ru or Ir catalysts, even when working under similar re-
action conditions.
The catalyst temporarily removes hydrogen from an alco-
hol to form the more reactive aldehyde and a metal hydride.
The aldehyde is converted in situ into an imine through a
condensation reaction with an amine. The hydrogen is given
to the imine, thereby yielding a new amine with the overall
À
formation of a C N bond.
We have found that the rate-controlling step of the pro-
cess is the hydrogenation of the imine by hydride transfer.
This reaction behaves as a structure-sensitive reaction with
respect to the Pd. According to this, both activity and selec-
tivity values are higher when the crystallite size is smaller.
Pd is more active and selective than Au or Pt on MgO.
Hydrogenation of the C=N double bond in the presence
of a C=C group has been studied by using allylic alcohols as
well as unsaturated alcohols as alkylating agents. In general,
we have observed that the steric hindrance and the position
of the double bond relative to the imine group are crucial in
determining the chemoselectivity for the unsaturated amine
with this catalytic system. In conjugated systems, we can
confirm that no transfer hydrogenation occurs for the imine
bond in the presence of the C=C bond, so that reduction of
the latter takes place with complete chemoselectivity. In
nonconjugated systems, a marked reduction of chemoselec-
tivity is observed, since now the C=N as well as the C=C
bond are simultaneously hydrogenated.
Since the reaction is applicable to the alkylation of ani-
lines as well as aliphatic amines, a closely related strategy
has been used to prepare piperazines through a new synthet-
ic route.
Interestingly, the monoalkylation reaction of the aliphatic
amine 1-cyclohexylethylamine with benzyl alcohol proceeds
rapidly. It affords products derived exclusively from the oxi-
dative dehydrogenation of the alcohol (see entry 7,
Table S2).
Experimental Section
Hydroxyapatite and hydrotalcite were prepared by following previously
reported procedures.[24,25] An MgO sample with
a
surface area of
670 m2 gÀ1 was purchased from NanoScale Materials. Inorganic salts [Pd-
(acac)2], NaAuCl4, and KAu(CN)2 were purchased from Aldrich, whereas
[Au(CH3)2A(acac)] and [Pt(acac)2] were supplied by Strem and Acros, re-
One-pot synthesis of piperazines: Owing to the success of
Pd/MgO in catalyzing the monoalkylation of aniline with al-
cohols, we have attempted the reaction between different
1,2-diamines and 1,2-diols to achieve the one-pot synthesis
of piperazines. The reactions were performed using equimo-
AHCTUNGTRENNUNG
G
G
ACHTUNGTRENNUNG
spectively. The products were used as received.
Preparation of metal/MgO (metal=Pd, Pt, Au) bifunctional catalysts:
Pd/MgO (0.8 wt% palladium) was prepared by following the procedure
258
www.chemeurj.org
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 254 – 260

Bifunctional Pd/MgO Solid Catalyst
FULL PAPER
reported in ref. [10]. Pt/MgO (1 wt% metal loading) was obtained by
adding MgO (1 g, 670 m2 gÀ1) to a solution of [Pt
ACTHNUTRGNE(UNG acac)2] (24.01 mg,
[1] a) Y. Watanabe, Y. Tsuji, H. Ige, Y. Ohsugi, T. Ohta, J. Org. Chem.
1984, 49, 3359–3363; b) R. A. T. M. Abbenhuis, J. Boersma , G.
Van Koten, J. Org. Chem. 1998, 63, 4282–4290; c) Y. Tsuji, K-T. Hu,
Y. Watanabe, Tetrahedron Lett. 1986, 27, 377–380; d) Y. Tsuji, K-T.
Hu, Y. Watanabe, J. Org. Chem. 1987, 52, 1673–1680; e) Y. Tsuji, S.
Kotachi, K-T. Hu, Y. Yokohama, Y. Watanabe, J. Org. Chem. 1990,
55, 580–584; f) Y. Watanabe, Y. Morisaki, T. Kondo, T. Mitsudo, J.
Org. Chem. 1996, 61, 4214–4218; g) D. Hollmann, S. Bahn, A. Till-
ack, R. Parton, R. Altink, M. Beller, Tetrahedron Lett. 2008, 49,
5742–5745.
0.078 mmol) in anhydrous dichloromethane (30 mL) while stirring for
12 h. After evaporation of the solvent at reduced pressure, the solid was
dried overnight at 353 K under vacuum and then calcined under a nitro-
gen flow at 823 K (ramp rate: 58CminÀ1) for 3.5 h. The sample was acti-
vated before reaction by heating the solid at 723 K under an atmosphere
of air for 5 h and then for 5 h under nitrogen. Metal reduction was per-
formed by heating the solid at 523 K in a flow of H2/N2 (90:10) for 2 h.
Au/MgO (1 wt% metal loading) was prepared by following a reported
procedure, albeit with modifications:[26] MgO (1 g, 670 m2 gÀ1) was added
[2] a) G. Cami-Kobeci, P. A. Slatford, M. K. Whittlesey, J. M. Williams,
Bioorg. Med. Chem. Lett. 2005, 15, 535–537; b) K. I. Fujita, T. Fujii,
R. Yamaguchi, Org. Lett. 2004, 6, 3525–3528; c) K. I. Fujita, Z. Li,
N. Ozeki, R. Yamaguchi, Tetrahedron Lett. 2003, 44, 2687–2690.
[3] a) M. H. S. A. Hamid, J. M. J. Williams, Chem. Commun. 2007, 725–
727; b) D. Hollmann, A. Tillack, D. Michalik, R. Jackstell, M. Beller,
Chem. Asian J. 2007, 2, 403–410; c) G. Jenner, G. Bitsi, J. Mol.
Catal. 1988, 45, 165–168; d) M. H. S. A. Hamid, C. L. Allen, G. W.
Lamb, A. C. Maxwell, H. C. Maytum, A. J. A. Watson, J. M. J. Wil-
liams, J. Am. Chem. Soc. 2009, 131, 1766–1774; e) K. Kujita, Y.
Enoki, R. Yamaguchi, Tetrahedron 2008, 64, 1943–1954; f) B. Blank,
S. Michlik, R. Kempe, Chem. Eur. J. 2009, 15, 3790–3799; g) J. L.
Garcꢁa Ruano, A. Parra, J. Aleman, F. Yuste, V. M. Mastranzo,
Chem. Commun. 2009, 404–406.
[4] a) R. M. Nieto, A. Coelho, A. Martinez, A. Stefanachi, E. Sotelo, E.
RaviÇa, Chem. Pharm. Bull. 2003, 9, 1025–1028; b) M. Vieth, M. G.
Siegel, R. E. Higgs, I. A. Watson, D. H. Robertson, K. A. Savin,
G. L. Durst, P. A. Hipskind, J. Med. Chem. 2004, 47, 224–232.
[5] J. S. Carey, D. Laffan, C. Thomson, M. T. Williams, Org. Biomol.
Chem. 2006, 4, 2337–2347.
to a solution of [AuACHTUNGTRENNUNG(CH3)2ACHTUTGNREN(NUGN acac)] (17.963 mg, 0.055 mmol) in ethanol
(30 mL) while stirring for 12 h. The solvent was evaporated at reduced
pressure. The solid was dried overnight at 353 K under vacuum and then
calcined in a nitrogen flow at 823 K (ramp rate: 58CminÀ1) for 3.5 h. The
sample was activated before reaction by heating the solid at 723 K under
air for 5 h and then for 5 h under nitrogen. Metal reduction was per-
formed by heating the solid at 523 K in a flow of H2/N2 (90:10) for 2 h.
Preparation of bimetallic supported catalysts (PdPt/MgO, AuPd/MgO,
AuPt/MgO):[27] AuPt/MgO (0.75 wt% Pt and 2.5 wt% Au) was prepared
by co-impregnation of MgO with two solutions of [Pt
ACHTUNGTERN(NGNU acac)2] (9.015 mg,
0.023 mmol) and [Au(CH3)2A(acac)] (25.15 mg, 0.077 mmol) in dichloro-
A
CHTUNGTRENNUNG
methane (15 mL). The mixture was stirred for 12 h at room temperature.
The solvent was evaporated at reduced pressure and the solid was dried
at 808C for 12 h under vacuum. The material was calcined at 4508C
under a N2 flow for 4.5 h (58CminÀ1). Metal reduction was performed by
heating the solid at 523 K in a flow of H2/N2 (90:10) for 2 h.
AuPd/MgO (0.75 wt% Pd and 2.5 wt% Au) was prepared by co-impreg-
nation of MgO with two solutions of [Pd
ACHTUNGERTN(NUNG acac)2] (12.795 mg, 0.042 mmol)
and [Au(CH3)2A(acac)] (25.15 mg, 0.077 mmol) in acetone (15 mL). The
A
CHTUNGTRENNUNG
mixture was stirred for 12 h at room temperature. The solvent was evapo-
rated at reduced pressure and the solid was dried at 808C for 12 h under
vacuum. The material was calcined at 4508C under a N2 flow for 4.5 h
(58CminÀ1). Metal reduction was performed by heating the solid at
523 K in a flow of H2/N2 (90:10) for 2 h.
[6] a) S. Soukara, B. Wꢄnch, Synthesis 1999, 1739–1746; b) M. E. Jung,
J. C. Rohloff, J. Org. Chem. 1985, 50, 4909–4913.
[7] a) C. Macleod, B. I. Martinez-Teipel, W. M. Barker, R. E. Dolle, J.
Comb. Chem. 2006, 8, 132–140; b) K. G. Liu, A. J. Robichaud, Tet-
rahedron Lett. 2005, 46, 7921–7922.
PdPt/MgO (0.75 wt% Pd and 0.1 wt% Pt) was prepared by co-impregna-
[8] a) P. Vairaprakash, M. Periasamy, J. Org. Chem. 2006, 71, 3636–
3638; b) G. J. Mercer, M. S. Sigman, Org. Lett. 2003, 5, 1591–1594.
[9] a) R. A. Sheldon, Green Chem. 2005, 7, 267–278; b) B. M. Trost,
Acc. Chem. Res. 2002, 35, 695–705.
[10] M. J. Climent, A. Corma, S. Iborra, M. Mifsud, J. Catal. 2007, 247,
223–230.
[11] Y. R. S. Laxmi, J.-E. Bꢅckvall, Chem. Commun. 2000, 611–612.
[12] a) J.-P. Deng, W.-C. Shih, C.-Y. Mou, ChemPhysChem 2005, 6,
2021–2025; b) A. S. K. Hashmi, R. Salathe, T. M. Frost, L. Schwarz,
J.-H. Choi, Appl. Catal. A 2005, 291, 238–246.
tion of MgO with two solutions of [Pd
ACHTUNGERTN(NUNG acac)2] (26.7 mg, 0.0888 mmol)
and [Pt(acac)2] (4.5 mg, 0.011 mmol) in dichloromethane (20 mL). The
ACHTUNGTRENNUNG
mixture was stirred for 12 h at room temperature. The solvent was evapo-
rated at reduced pressure and the solid was dried at 808C for 12 h under
vacuum. The material was calcined at 4508C under a N2 flow for 4.5 h
(58CminÀ1). Metal reduction was performed by heating the solid at
523 K in a flow of H2/N2 (90:10) for 2 h.
Catalyzed N-alkylation of amines with alcohols: A mixture of alcohol
(1 mmol), amine (3 mmol), Pd/MgO (0.0998 g; Pd: 0.0075 mmol), trifluo-
ACHTUNGTRENNUNGroACHTUNGTRENNUNGtoluene (1 mL), and n-dodecane (20 mL) as internal standard were
[13] a) M. C. Gimeno, A. Laguna in Comprehensive Coordination
Chemistry II, Vol. 6 (Ed.: D. E. Fenton), Elsevier, Amsterdam,
Chapter 6.7, p. 911; b) R. J. Puddephatt in Comprehensive Coordina-
tion Chemistry, Vol. 5 (Ed.: G. Wilkinson), Elsevier, Amsterdam,
Chapter 55, p. 861.
placed into an autoclave. The resulting mixture was vigorously stirred at
1808C under nitrogen. The reaction was monitored by GC.
Study of the monohydride and/or dihydride mechanism: Pd/MgO
(147.3 mg, 0.8%) and PhCD2OH (125.8 mg) were added into an auto-
clave containing trifluorotoluene (1 mL) under nitrogen. The reaction
mixture was heated at 1808C while being vigorously stirred. The reaction
was monitored by GC. The catalyst was filtered off (after 1.5 h) and tri-
fluorotoluene was eliminated with heating under reduced pressure. The
1H and 13C NMR spectra of the reaction mixture were recorded using
[D6]DMSO as solvent and TMS as the internal reference.
[14] G. N. Khairallah, R. A. J. OꢆHair, M. I. Bruced, Dalton Trans. 2006,
3699–3707.
[15] a) R. H. Crabtree in Modern Coordination Chemistry (Eds.: G. J.
Leigh, N. Winterton), RSC, Cambridge, 2002; b) R. H. Crabtree in
Recent Advances in Hydride Chemistry (Eds.: M. Peruzzini, R. Poli),
Elsevier, Amsterdam, 2001; c) R. H. Crabtree in Transition Metal
Hydrides (Ed.: A. Dedieu), VCH, Weinheim, 1992.
[16] For a review on gas-phase transition-metal hydrides, see: P. B. Ar-
mentrout, L. S. Sunderlin in Transition Metal Hydrides (Ed.: A.
Dedieu), VCH, Weinheim, Chapter 1k, 1992.
[17] J. S. M. Samec, A. H. Ell, J.-E. Bꢅckvall, Chem. Eur. J. 2005, 11,
2327–2334.
Acknowledgements
[18] a) E. Suchanek, N. Lange, G. Auffermann, W. Bronger, H. D. Lutz,
J. Raman Spectrosc. 1999, 30, 981–986; b) Raman studies, which are
a valuable tool in elucidating the relative strength of metal–hydro-
gen (MH) bonds in transition-metal hydrido complexes, confirms
that MH stretching modes display much stronger bonds in the case
Financial support by the Direcciꢀn General de Investigaciꢀn Cientꢁfica y
Tꢃcnica of Spain (project MAT2006-14274-C02-01), Generalitat Valenci-
ana (project PROMETEO/2008/130), and Fundaciꢀn Areces is gratefully
acknowledged. T.R. thanks Consejo Superior de Investigaciones Cientꢁfi-
cas for I3-P fellowships.
Chem. Eur. J. 2010, 16, 254 – 260
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
259

A. Corma, T. Rꢀdenas, and M. J. Sabater
of 5d metal atoms than the 3d and 4d metal atoms; c) P. Pyykkç,
Chem. Rev. 1988, 88, 563–594.
Soc. Rev. 2006, 35, 237–248; c) Y. R. S. Laxmi, J.-E. Bꢅckvall, Chem.
Commun. 2000, 611–612; d) J. E. Bꢅckvall, J. Organomet. Chem.
2002, 652, 105–111.
[19] a) N. Mahata, V. Vishwanathan, J. Catal. 2000, 196, 262–270; b) S.
Domꢁnguez-Domꢁnguez, A. Berenguer-Murcia, A. Linares-Solano,
D. Cazorla-Amorꢀs, J. Catal. 2008, 257, 87–95; c) R. Van Hardeveld,
F. Hartog, Surf. Sci. 1969, 15, 189–230; d) R. E. Benfield, J. Chem.
Soc. Faraday Trans. 1992, 88, 1107–1110.
[25] a) K. Mori, T. Hara, T. Mizugaki, K. Ebitani, K. Kaneda, J. Am.
Chem. Soc. 2004, 126, 10657–10666; b) A. Abad, C. Almela, A.
Corma, H. Garcꢁa, Tetrahedron 2006, 62, 6666–6672; c) C. Elliot,
Structure and Chemistry of the Apatites and Other Calcium Ortho-
phosphates, Elsevier, New York, 1994; d) S. Sugiyama, T. Minami,
H. Hayashi, M. Tanaka, N. Shigemoto, J. B. Moffat, J. Chem. Soc.
Faraday Trans. 1996, 92, 293.
[26] M. J. Climent, A. Corma, S. Iborra, K. Epping, A. Velty, J. Catal.
2004, 225, 316–326.
[27] Y. Hao, M. Mihaylov, E. Ivanova, K. Hadjiivanov, H. Knçzinger,
B. C. Gates, J. Catal. 2009, 261, 137–149.
[20] M. Boudart, Chem. Rev. 1995, 95, 661–666.
[21] a) A. Corma, H. Garcꢁa, A. Leyva, Mol. Catal. A 2005, 230, 97–105;
b) A. Corma, H. Garcꢁa, A. Leyva, J. Catal. 2004, 225, 350–358.
[22] W. Grochala, P. P. Edwards, Chem. Rev. 2004, 104, 1283–1316.
[23] a) E. Knçzinger, K. H. Jacob, P. Hofmann, J. Chem. Soc. Faraday
Trans. 1993, 1101; b) W. M. Bartczak, J. Stawowska, Mater. Sci.-Pol.
2006, 24.
[24] a) O. Pꢇmies, J-E. Bꢅckvall, Chem. Eur. J. 2001, 7, 5052–5058;
b) J. S. M. Samec, J.-E. Bꢅckvall, P. G. Andersson, P. Brandt, Chem.
Received: June 3, 2009
Published online: November 10, 2009
260
www.chemeurj.org
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 254 – 260