New one-pot multistep process with multifunctional catalysts: Decreasing the e factor in the synthesis of fine chemicals

Article abstract of DOI:10.1039/b919660a

The synthesis of a series of fine chemicals (4-(4-methoxyphenyl)-2- butanone, 4-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)-2-butanone, and 2-cyclopentylcylopentanone) has been performed through a simple process that involves one-pot multi-step reactions (condensation-dehydration-reduction) using multifunctional base-acid-metal catalysts. The E factor for the specific process, as well as for the global process that includes the manufacturing of the reactants, has been calculated and compared with those obtained using conventional methods. In various cases, it is demonstrated that by means of process intensification with multifunctional solid catalysts, it is possible to decrease the E factor by one order of magnitude or more with respect to any of the manufacturing routes reported to date.

Full text of DOI:10.1039/b919660a

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www.rsc.org/greenchem | Green Chemistry
New one-pot multistep process with multifunctional catalysts: decreasing
the E factor in the synthesis of fine chemicals†
Maria J. Climent, Avelino Corma,* Sara Iborra, Maria Mifsud and Alexandra Velty
Received 29th April 2009, Accepted 22nd September 2009
First published as an Advance Article on the web 26th October 2009
DOI: 10.1039/b919660a
The synthesis of a series of fine chemicals (4-(4-methoxyphenyl)-2-butanone,
4-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)-2-butanone, and 2-cyclopentylcylopentanone) has
been performed through a simple process that involves one-pot multi-step reactions
(condensation–dehydration–reduction) using multifunctional base–acid-metal catalysts. The E
factor for the specific process, as well as for the global process that includes the manufacturing of
the reactants, has been calculated and compared with those obtained using conventional methods.
In various cases, it is demonstrated that by means of process intensification with multifunctional
solid catalysts, it is possible to decrease the E factor by one order of magnitude or more with
respect to any of the manufacturing routes reported to date.
Metal supported on alkaline earth layered double hydroxides
(LDH) and its mixed oxides have been extensively applied as
Introduction
In the late 1980s, Sheldon1 introduced the concept of the E
multifunctional base–acid-metal catalysts for cascade reactions
(environmental) factor for assessing the environmental impact
such as the synthesis of methyl isobutyl ketone in one pot
of manufacturing processes. The E factor is defined as the mass
from acetone19-23 or from 2-propanol24-27 and for the preparation
ratio of waste to the desired product (kg waste/kg product).
of fine chemicals such as 2-methyl-3-phenyl propanal,28,29 a-
To calculate the E factor, the chemical yield, reagents, solvent
alkylated nitriles,30 and the anti-inflamatory nabumetone.11,16
losses, all process aids, and even energy consumption (though
Here, we present that by means of multifunctional base–
this is frequently difficult to estimate) are taken into account. The
acid-metal catalysts (Pd-supported alkaline earth oxides and
water used in the process is not considered, but water formed is
mixed oxides), it is possible to substitute existing processes
included in the calculations. Catalysis plays an important role in
for the production of a series of fine chemicals (4-(4-
reducing or eliminating waste in chemical processes, particularly
methoxyphenyl)-2-butanone, 4-(6,6-dimethylbicyclo[3,1,1]hept-
for the production of fine chemicals, where the E factors are
2-en-2-yl)-2-butanone, and 2-cyclopentylcylopentanone) by a
especially high. Most of the waste generated in the manufacture
more simple process that involves one-pot multi-step reactions.
of fine chemicals is inorganic salts formed by the use of stoichio-
We show that by means of process intensification with multi-
metric inorganic reagents. Thus, the substitution of conventional
functional solid catalysts, it has been possible, in various cases,
stoichiometric methodologies by catalytic processes, combined
to decrease the E factor by one order of magnitude or more,
with the possibility of intensifying processes by combining
with respect to any of the manufacturing routes reported up to
several catalytic steps into a one-pot catalytic system, provides a
now. In this work, the E factor for the specific process as well
means to improve the economical and environmental aspects
as for the global process that includes the manufacturing of the
of chemical processes. In this sense, domino catalytic multi-
reactants has been considered.
step reactions with mono- or multifunctional catalysts are very
efficient processes in terms of work up and catalyst utilization,
with the additional advantage that isolation and purification
Results and discussion
of intermediates is not required.2–12 Moreover, the fact that the
1. Preparation of 4-(4-methoxyphenyl)-2-butanone (2)
same catalyst can catalyze different consecutive steps in a single
reaction vessel under the same reaction conditions decreases
4-(4-Methoxyphenyl)-butan-2-one (2) (Scheme 1) is an odorous
the operating time and the amount of waste produced. In this
molecule with a raspberry scent which is extracted from aloe
way, heterogeneous catalysts containing various active sites on
wood, and has been approved by the FDA for food uses at a
their surface are promising candidates for promoting multiple
level of 25 ppm. It has also been utilized as an insect attractant
for the scarabaeid family and in the preparation of melanin
formation inhibitors.31 One route for the preparation of 2 in
reactions in a single pot.13-18
one step (Scheme 1) is the Friedel–Crafts alkylation of anisole
with 4-hydroxybutan-2-one or methyl vinyl ketone using acid
catalysts such as H2SO4, H3PO4, HCl.32 However, many side
reactions (transalkylations, isomerization, polyalkylation and
polymerization) occur during Friedel–Crafts alkylation in the
Instituto de Tecnolog´ıa Quimica, Universidad Polite´cnica de Valencia,
Avda. de los Naranjos s/n, 46022 Valencia, Spain.
E-mail: acorma@itq.upv.es
† Electronic supplementary information (ESI) available: Details of E
factor calculations. See DOI: 10.1039/b919660a
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Scheme 1
Scheme 2
Table 1 Results for the synthesis of 2 using different multifunctional
presence of Lewis or Brønsted homogeneous acid catalyst,
resulting in a maximum selectivity for 2 of approximately 70%.
Heterogeneous catalysts, such as exchanged resins (Dowex-
50),33 have also been used for this transformation, however
low selectivity for 2 (60–70%) was obtained. Cation exchanged
montmorillonite also containing Brønsted acid sites has been
utilized, yielding only 25% of 2 at 100 ◦C after 48 h reaction
time.34
catalysts
r◦ ¥ 104/mmol Conversion Yield Yield Selectivity
Catalysts min-1 g-1
(%)
1 (%) 2 (%) 2 (%)
PdMgO
PdHTc
PdHTr
12.0
5.0
9.7
100
89
95
1
25
—
99
62
95
99
68(2)
100
r◦: rate of disappearance of 4-methoxybenzaldehyde. Reaction condi-
tions: 4-methoxybenzaldehyde (3.8 mmol), acetone (37 mmol); 75 ◦C,
catalyst 38 wt% with respect to anisaldehyde. Conversion and yield at
75 min reaction time. The value in brackets is the percentage of Michael
adduct.
There is another route to synthesize 2 (Scheme 2), that involves
an aldol condensation between 4-methoxybenzaldehyde and
acetone, yielding the a,b-unsaturated compound 1, which is
=
followed by hydrogenation of the C C bond in a two-step
reaction. When using homogenous catalysts, the condensation
step has been carried out with NaOH as catalyst yielding 98%
of the a,b-unsaturated ketone (1).35 While a one-pot process has
been carried out under hydrogen atmosphere, in the presence
of NaOH and 5% Pd/C, the two step process yields 80% of
4-(4-methoxyphenyl)-2-butanone (2).36
(PdHTr) which were tested under the same reaction conditions
as PdMgO.
As can be seen in Table 1, PdHTc exhibits lower condensation
and hydrogenation rates than PdMgO and, consequently, the
yield and selectivity of 2 are lower. Moreover, a secondary
product resulting from the Michael addition of acetone to 2 was
also detected in minor amounts. When the calcined hydrotalcite
containing palladium metal was rehydrated (PdHTr), a twofold
increase in initial reaction rate was observed. This result
is not surprising since by rehydration, a restoration of the
We propose here an alternative one-pot catalytic process to
synthesize 2 that consists of reacting 4-methoxybenzaldehyde
with acetone under hydrogen atmosphere in the presence
of PdMgO catalyst to give an intermediate, 1, which is
hydrogenated to give 2 (Scheme 2). The reaction between
4-methoxybenzaldehyde and acetone was performed using
1 wt% of Pd loaded on the nanocrystalline MgO (see Exper-
2-
layered structure occurs wherein the CO3 counter anions in
◦
the interlayer space are replaced by OH-, resulting in strong
Brønsted base catalysts that efficiently catalyze a larger number
of reactions.38–45 Results in Table 1 indicate that, together with
PdMgO, PdHTr is a promising candidate for the preparation of
2, since 95% yield with 100% selectivity is obtained after 75 min
reaction time.
imental) at 75 C. The results in Table 1 show that PdMgO is
able to convert 100% of 4-methoxybenzaldehyde, giving 99%
yield and 99% selectivity for 2.
It is known that the selection of the most appropriate type of
centres for a given base-catalyzed process has a strong impact
on the catalyst activity and selectivity.37 Thus, we have also
prepared two Pd catalysts supported on Al/Mg calcined hydro-
talcite (PdHTc) and on calcined–rehydrated Al/Mg hydrotalcite
Nevertheless, for a potential industrial implementation of the
above catalysts (PdMgO and PdHTr) for the preparation of 2,
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Table 2 Study of the stability of the catalysts
Table 3 Summary of the E factors for the synthesis of 2 through aldol
condensation
Conversion
(%)
Yield
1 (%)
Yield
2 (%)
Selectivity
2 (%)
Catalysts
PdHTr
Cycles
E factor
E factor
(heterogeneous)a
(homogeneous)a
1
2
1
2
3
4
95
25
100
100
100
100
—
18
1
2
1
95
7
99
98
99
98
100
28
99
98
99
98
Compound
via i
via ii
via i
via ii
PdMgO
0.78
0.78
2
the possibility of catalyst regeneration has to be considered.
To study the reusability of the catalysts, the samples were
regenerated after the reaction as described in the Experimental
section and the catalyst was used again. As it can be seen in
Table 2, an important decrease in activity upon regeneration
was found with the PdHTr sample, which is probably due to an
incomplete reconstruction and/or a decrease in the number of
basic and hydrogenating active sites. In contrast, the PdMgO
sample was subjected to four cycles of reaction–regeneration
(calcination)–reaction, in all cases achieving 100% conversion
and similar selectivity of 2 (Table 2).
0.04
2.77
0.04
2.77
CH3COCH3
0.16
0.01
0.16
0.01
0.16
9.69
0.16
9.69
In conclusion, we have shown that by using a multifunctional
catalyst based on Pd supported on nanocrystalline MgO, it has
been possible to develop a new green process for production of 2
in a one-pot cascade reaction. This new process allows yields of
99% with 99% selectivity for 2. The E factor involved is presented
below.
2
Global E factor
0.99
2.94
10.67
12.62
a Referring to the specific path for the synthesis of 2
These results indicate that considering the global process
starting from p-cresol, the E factor for the procedure presented
here with PdMgO is one order of magnitude lower than that of
the conventional process (see Table 3). In Table 3, the specific
E factors of all compounds involved in the production of
compound 2 are summarized, as well as the global E factors
following routes i and ii, performed using heterogeneous and
homogeneous catalysts in the specific path for the synthesis
of 2.
We have also considered here another potential procedure for
the synthesis of 2 through two consecutive steps, involving a
Heck coupling reaction between p-iodoanisole and methyl vinyl
ketone (MVK) followed by hydrogenation (see Scheme 4). It
has been reported that the synthesis of 2 via Scheme 4 could
be performed in a one pot, two-step process using palladium
supported on titanium dioxide as a catalyst. Under optimized
reaction conditions, this catalytic route gave 2 with 97% yield.12
Thus, for comparison purposes we have calculated the E factor
for the synthesis of compound 2 through the Heck coupling
reaction under heterogeneous and homogeneous catalysis, and
the result, considering that the solvent can be fully recycled, is
1.96 (Scheme 4).
1.1 E factor for the synthesis of 4-(4-methoxyphenyl)-2-
butanone (2). We have calculated the E factor for the specific
process described above (Scheme 2), as well as the global E factor
when starting from primary organics such as methyl phenol or
anisole (Scheme 3).
Considering that acetone is an easily recoverable solvent and
the hydrogenation process does not produce any waste, the
E factor for the one-pot reaction starting from p-methoxy-
benzaldehyde is 0.01, water being the main waste. The E factors
for the syntheses of the reagents, acetone and 4-methoxy-
benzaldehyde, have also been calculated. For the synthesis of
acetone we have selected the cumene route starting from benzene
and propylene since this is the main industrial method used
to produce acetone (see the ESI†). The total E factor for the
production of acetone is 0.16.
On the other hand, the value for 4-methoxybenzaldehyde has
been obtained according to two different routes (Scheme 3):
(i) by methylation of p-cresol giving p-methoxytoluene fol-
lowed by catalytic oxidation with air, which has an E factor of
0.82 (see the ESI†).
(ii) by formylation of anisole through a Vilsmeier reaction,46
which has an E factor of 2.77 (see the ESI†). If we consider the
global process, via i and via ii, the global E factors are 0.99 and
2.94, respectively (see Table 3).
If we follow the same methodology for the commercially
accepted process where the aldol condensation is carried out
using a 10% aqueous solution of NaOH35 (see Scheme 3),
the specific E factor is 9.69, and when considering the global
process, via i and via ii, the global E factors are 10.67 and 12.62,
respectively (see Table 3).
The waste produced during the synthesis of the reagents
in Scheme 4 is also considered and, since the synthesis of 4-
iodoanisole can be carried out by different methodologies, for
calculation of the E factor we have selected a green process
recently reported by Earle et al.47 which has an E factor of 0.30
(see the ESI†) This value is lower than E = 0.80 calculated when
the iodation of anisole was performed with N-iodosuccinimide48
as the iodating agent in acetonitrile as solvent.
The second reactant, i.e. methyl vinyl ketone, is pro-
duced through the aldol condensation between acetone and
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Scheme 3
Scheme 4
formaldehyde. The process can be carried out in either the gas
phase or liquid phase. In the liquid phase,49 the E factor is 0.99,
while in the gas phase50 the E factor is 0.60 (see the ESI†).
If we accept the greener, gas phase process for calculating the
global E factor for the formation of the 4-(4-methoxyphenyl)-
2-butanone via Heck coupling, the calculated value is E = 2.86
(see the ESI†). When this value is compared to that obtained
during the aldol condensation with the solid catalyst (Scheme 3)
in a one-pot reaction, it can be concluded that the heterogeneous
Heck process produces about three times more waste than the
heterogeneous aldol condensation.
Finally, we have considered that the synthesis 4-(4-
methoxyphenyl)-2-butanone (2) can also be achieved through
the Heck reaction by coupling an aryl halide with a a-
methylene-b-hydroxy compound in the presence of a Pd com-
plex catalyst (Scheme 5). Specifically, the process involves
the reaction between p-bromoanisole and methyl-3-hydroxy-2-
methylene butyrate using a tetraphosphine palladium complex
as a catalyst, in DMF as a solvent and in the presence of K2CO3
or NaHCO3. The yield reported for 4-(4-methoxyphenyl)-2-
butanone is 87%.51 The calculated E factor for the specific
process, considering the solvent recoverable, is 3.11 (Scheme 5).
The E factor involved in the preparation of the tetraphosphine
palladium catalyst has not been considered here.
are 0.21 and 0.77, respectively (see the ESI†). Considering
these two values, plus the value for the reaction in Scheme 5,
the global E factor for the preparation of raspberry scent
following Scheme 5 is 4.09. This is about 1.5¥ higher than the
heterogeneous process described above, and approximately 5¥
higher than the one-pot process using the PdMgO catalyst.
In Table 4 the specific E factors of each compound involved in
the synthesis of 2 are summarized as well as the global E factor
for the heterogeneous and homogeneous Heck coupling rection.
In conclusion,
a
new synthetic process for 4-(4-
methoxyphenyl)-2-butanone with raspberry scent has been
outlined that involves a one-pot process with a multifunctional
(metal acid–base) solid catalyst and which has a much lower E
factor than any reported before.
2. Preparation of 4-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)-
2-butanone (3)
Terpenes are important compounds for the fragrance and
flavour industry. The terpenic compound 4-(6,6-dimethyl-
bicyclo[3,1,1]hept-2-en-2-yl)-2-butanone (3) (Scheme 6), is used
as perfume and possesses activity as an insect juvenile
hormone.52 The conventional preparation of 3 is carried out
through the acetoacetic reaction between myrthenyl bromide
and ethyl acetoacetate in the presence of stoichiometric amounts
of sodium ethoxide at the reflux temperature of ethanol yielding,
On the other hand, the calculated E factors for the preparation
of p-bromoanisole and methyl-3-hydroxy-2-methylene butyrate
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Scheme 5
Scheme 6
Table 4 Summary of the E factors for the synthesis of 2 through the
refluxing for 18 h with barium hydroxide in aqueous ethanol
giving 3 in 85% yield.53
Heck coupling reaction
We have calculated the E factor of each step of the
process given in Scheme 7, starting from b-pinene, whose
bromination to myrthenyl bromide can be accomplished with
N-bromosuccinimide in refluxing CCl4, yielding 51% of
myrthenyl bromide.54 Taking into account that solvent and
unreacted b-pinene are recoverable, we have calculated an E
factor of 1.18 for the production of myrthenyl bromide. On the
other hand, the second reactant involved, i.e., ethyl acetoacetate,
can be produced by a solvent-free Claisen condensation of ethyl
E factor
E factor
Compound
(heterogeneous)a Reactant
0.30
(homogeneous)a
0.21
=
CH2 CHCOCH3 0.60
0.77
3.11
t
acetate in the presence of BuOK that yields 75% of ethyl
acetoacetate. The calculated E factor for this reaction is 2.78.
Thus, the E factor of the global process presented in Scheme 7
to prepare the desired product, 3, is 5.45.
1.96
An alternative synthetic approach is presented here
(Scheme 8), in which 3 can be prepared in a one-pot cascade re-
action which involves an aldol condensation between myrthenal
and acetone, followed by dehydration of the aldol formed, and
selective double bond hydrogenation. For calculating the E
factor of the process, it has been considered that myrthenal
can be obtained by oxidation of a-pinene with SeO2.55 The
oxidation of a-pinene is carried out with equimolar amounts
of SeO2 in the presence of a solvent such as ethanol yielding
50% of myrthenal. The E factor for this step (see Scheme 8),
considering that both ethanol and the remaining a-pinene can
Global E factor 2.86
4.09
a Referring to the specific path for synthesis of 2.
after 4 h, 78% of ethyl 3-oxo-2-(2-pinen-10-yl) butyrate. Thus,
in a second synthetic step, the ketoester is decarboxylated by
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Scheme 7
Table 5 Summary of the E factors for the synthesis of 4
be recycled, is 1.3. The E factor for the global process given
in Scheme 8 is therefore 1.6. This value is 3.4¥ lower than the
homogeneous process described previously for the preparation
4-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)-2-butanone (3).
E factor
(heterogeneous)
E factor
(homogeneous)
Compound
4
0.10
1.16
3. Preparation of 2-cyclopentylcylopentanone (4)
The product 2-cyclopentylcylopentanone (4) with a jasmine-
like smell is used for perfume or flavouring56 and as a wood
preservative.57 2-Cyclopentylcyclopentanone can be synthesized
by different multi-steps methods, for instance by the acy-
loin condensation of dimethyl glutarate in the presence of
sodium (Scheme 9).58 However, the preferred method in terms
of yield and availability of starting materials, involves the
condensation of cyclopentanone in the presence of a basic
catalyst (NaOH, KOH or sodium) followed by the hydro-
genation of the resulting 2-cyclopentilydene-cyclopentanone
in the presence of a hydrogenating catalyst such as Pd/C59
(Scheme 10). Thus, by reacting cyclopentanone at 90 ◦C in
the presence of a 10% aqueous solution of NaOH, a 54%
yield of 2-cyclopentilydene-cyclopentanone (5) was obtained
after 3 h reaction time. After purification by distillation at
reduced pressure, the compound is hydrogenated using palla-
dium (5 wt%) on activated carbon as catalyst, yielding 89% of
2-cyclopentylcyclopentanone (4). The main drawback associ-
ated with this methodology is, in general, the low yields of
2-cyclopentilydene-cyclopentanone (6) achieved, due to the fact
that the self-condensation product can further condense with a
second cyclopentanone molecule to form the highly conjugated
trimer adduct (2,5-dicyclopentylidenecyclopentanone) (6). Due
to the high thermodynamic stability of the conjugated trimer
adduct, this compound is formed in important amounts that,
depending on reaction conditions, can reach to between 30 and
50%.60
be avoided or, at least, could be strongly diminished, giving
a higher final selectivity to 2-cyclopentylcylopentanone (5)
(Scheme 10). To do this, cyclopentanone was reacted in the
presence of PdMgO under a constant hydrogen pressure at
140 ◦C. After 8 h reaction time, the conversion was 98%
with 91% selectivity for 4. Under our reaction conditions,
the hydrogenated trimer (2,5-dicyclopentylcyclopentanone) (6)
and 2-cyclopentylcylopentanol were also detected, with yields
of 10 and 2%, respectively. The higher selectivity towards 4
achieved in this case, with respect to the conventional procedure,
demonstrates the advantage of the one-pot cascade process
using the PdMgO catalyst. In this case, it appears that the
fast hydrogenation of the intermediary, 2-cyclopentilydene-
cyclopentanone, diminishes the rate of the subsequent aldol
condensation that leads to the undesired highly-conjugated
trimer.
As shown in Scheme 10, the E factor for the heterogeneous-
catalyzed, one-pot cascade process is one order of magnitude
lower than the conventional method.
Table 5 summarizes the E factors for the synthesis of 4 using
heterogeneous and homogeneous catalysts.
It appeared to us that if the reaction was performed in
a one-pot system in which the rate of hydrogenation of
the condensation product was very high, then the second
condensation that leads to formation of the trimer (6) could
Conclusions
We have illustrated here that process intensification by
means of multifunctional solid catalysts that allow one-pot
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Scheme 8
Scheme 9
Scheme 10
cascade reactions, opens new, more environmentally benign
routes than those currently used for the synthesis of fine
chemicals.
Experimental
Preparation of catalysts
Since, in many cases, the new routes proposed require starting
from different reactants than the conventional routes, we have
also calculated the E factor for the global process starting from
the primary products. It has been seen that, in most cases,
the new one-pot cascade reactions have E factors which are
one order of magnitude lower. The differences in the E factor
can be even larger if one considers the energy involved and
even the investments, since the one-pot processes do not require
intermediate separations.
Finally, it has been shown that, in some cases, higher
selectivities can be achieved in the one-pot cascade reactions
with multifunctional catalysts, by adjusting the relative rates of
the different consecutive steps.
A nanocrystalline MgO sample was purchased from NanoScale
Materials Inc.
The magnesium–aluminium layered double hydroxide sample
(Mg–Al LDH) was prepared from a gel produced by mixing
two solutions, A and B. Solution A contained (3 - x) mol of
Mg(NO3)2·6H2O and x mol of Al(NO3)3·9H2O in the (Al + Mg)
concentration of 1.5 mol L-1 for an Al/(Al + Mg) molar ratio of
0.25. Solution B was formed by (6 + x) mol of NaOH and 2 mol
of Na2CO3 dissolved in the same volume as solution A. Both
solutions were co-added at a rate of 1 mL min-1 under vigorous
mechanical stirring at room temperature. The gel was aged under
autogeneous pressure conditions at 333 K for 12 h. Then, the
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Table 6 Selected physical parameters for the catalysts used in the study
hydrotalcite was filtered and washed until pH = 7 and the solid
was dried. The Mg–Al mixed oxide (HTc) base catalyst was
obtained by calcination of Mg–Al-LDH at 723 K for 6 h in a
dry nitrogen flow.
Average
pore
diameter/A
Surface
Total pore
Crystall
˚
Catalyst
area/m2 g-1
volume/cc g-1
size/nma
Pd catalysts at 1 wt% loading were obtained by exposing
the Mg–Al-LDH or MgO samples to an anhydrous toluene
solution with the required amount of palladium acetylacetonate
(Pd(OAc)2) for 12 h. After evaporation of toluene at reduced
pressure, the solid was dried overnight at 80 ◦C in vacuum and
then calcined in nitrogen flow at 550 ◦C for 3.5 h. These samples
were denoted as PdHTc (calcined hydrotalcite) and PdMgO
The PdHTc sample was rehydrated at room temperature by
direct addition of decarbonated water (MilliQ) (36 wt%) just
before their use as catalyst, and was labelled as PdHTr.
Samples of PdMgO and PdHTc were activated before reaction
by heating the solid at 450 ◦C under air for 5 h and then 5 h under
nitrogen. Reduction of the Pd(II) was performed by heating the
solid at 450 ◦C in a flow of H2/N2 (90/10) for 2 h.
The catalysts prepared were characterized by XRD (Fig. 1),
TEM and nitrogen adsorption. N2 adsorption/desorption
isotherms were performed at 77 K in an ASAP 2010 appara-
tus from Micromeritics, after pre-treating the samples under
vacuum at 673 K overnight and the BET surface areas were
obtained using the BET methodology. The main characteristics
of the catalysts are given in Table 6.
PdHTc
PdHTr
PdMgO
258
21
670
0.543
—
0.644
86
—
39.55
< 50
—
3
a Crystallite size measured by X-ray diffraction.
Packard GC 5988 A with FID detector and a HP-5 capillary
column of 5% phenylmethylsilicone. In all the experiments,
dodecane was used as an internal standard. At the end of
the reaction, after cooling, the reaction mixture was filtered
to remove the catalyst. The solid was extracted thoroughly
in a Soxhlet apparatus using methanol as a solvent and the
extract considered in the mass balance. The reaction mixture was
concentrated under reduced pressure and the reaction products
were analyzed by GC-MS (Varian Saturn II, using the same
1
column as GC) and H NMR spectroscopy (Varian Gemenis-
300 MHz, CDCl3 as a solvent).
One-pot synthesis of 4-(4-methoxyphenyl)2-butanone (2)
4-methoxybenzaldehyde (3.8 mmol), was reacted with acetone
(37 mmol) in the presence of PdMgO (1 wt% of Pd) (38 wt% with
respect to 4-methoxybenzaldehyde) under constant hydrogen
pressure (5 bar) at 75 ◦C. After 75 min reaction time, 100%
conversion of 4-methoxybenzaldehyde with 99% selectivity for
2 was obtained.
One-pot synthesis of 4-(6,6-dimethylbicyclo[3,1,1]hept-
2-en-2-yl)-2-butanone (3)
Myrthenal (3.9 mmol) was reacted with acetone (48 mmol) in
the presence of PdMgO (1 wt% of Pd) (34 wt% with respect◦to
myrthenal) under constant hydrogen pressure (5 bar) at 75 C
for 3 h. The target molecule was obtained in 95% yield.
One-pot synthesis of 2-cyclopentylcylopentanone (4)
Cyclopentanone (10.7 mmol) was reacted in the presence of
PdMgO (21 wt%) under a constant hydrogen pressure (5 bar) at
◦
140 C during 8 h. A 98% conversion of cyclopentanone with
91% selectivity for 4 was achieved.
Regeneration of the catalysts
PdHTr and PdMgO samples were regenerated after each use
by calcination of the solids at 450 ◦C under air atmosphere for
5 h and then under nitrogen for 5 h. Reduction of the Pd was
performed by heating the solid at 450 ◦C in a flow of H2/N2
(90/10) for 2 h.
Fig. 1 XRD patterns of the solid catalysts.
Reaction procedure
For a typical experiment, the reactants were placed in a batch
slurry reactor which was immersed in a thermostated silicone
oil bath and magnetically stirred. When the temperature was
reached, the catalyst was added and hydrogen was applied at a
constant hydrogen pressure of 5 bar. The course of the reaction
was followed by gas chromatography (GC) using a Hewlett
Acknowledgements
The authors thank CICYT for financial support (Project MAT
2006-14274-C02-01). The contribution of Mr Pablo Ramos
to the experimental work reported herein is also gratefully
acknowledged.
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30 K. Motokura, N. Fujita, K. Mori, T. Mizugapi, K. Ebitani and K.
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