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al 339 (2008) 84–92
Applied Catalysis A: GenerSupported rhodium nanoparticles obtained by Metal Vapour Synthesis
as catalysts in the preparation of valuable organic compounds
Claudio Evangelisti a,b, Nicoletta Panziera a,b, Maria Vitulli b,1, Paolo Pertici a,*,Federica Balzano b, Gloria Uccello-Barretta a,b, Piero Salvadori a,b
a Istituto di Chimica dei Composti Organo-Metallici, ICCOM-CNR, Sezione di Pisa, via Risorgimento 35, 56126 Pisa, Italyb Dipartimento di Chimica e Chimica Industriale, Universita di Pisa, via Risorgimento 35, 56126 Pisa, Italy
Received 23 November 2007; received in revised form 10 January 2008; accepted 14 January 2008
Available online 18 January 2008
Abstract
Rhodium nanoparticles, derived from mesitylene-solvated rhodium atoms, deposited on g-Al2O3, are excellent catalysts for the selective
hydrogenation of the double bond in a,b-unsaturated carbonyl compounds. The low metal loading Rh on g-Al2O3 catalyst, containing
trioctylamine, TOA, as stabilizing agent of the metal nanoparticles, Rh(TOA)/g-Al2O3, 0.1 wt.% Rh, showed the highest catalytic activity.
Using this catalyst 4-(6,-methoxy-2,-naphthyl)-3-buten-2-one was reduced to the anti-inflammatory drug 4-(6,-methoxy-2,-naphthyl)-butan-2-one,
NabumetoneTM, with complete selectivity and under mild reaction conditions (room temperature, atmospheric pressure of hydrogen). Similarly, 2-
acetyl-5,8-dimethoxy-3,4-dihydronaphthalene was hydrogenated with high selectivity (85%) to 2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-
naphthalene, precursor of antitumor anthracyclinic compounds, which was obtained chemically pure by crystallization. No leaching of rhodium
was observed. The catalyst was completely recovered and, if reused, it works without loss of activity. 1H NMR DOSY analysis of the Rh(TOA)/
mesitylene solution evidenced the presence of nanoparticles with a diameter of about 1.1 nm.
# 2008 Elsevier B.V. All rights reserved.
Keywords: Supported rhodium nanoparticles; Metal Vapour Synthesis; Selective hydrogenation; a,b-Unsaturated ketones; 1H NMR DOSY analysis
1. Introduction
A great deal of attention is currently being given to the study
of nanostructured metal catalysts [1–3]. Their chemical
behaviour is strongly related to the particle size; clusters
averaging 1–2 nm in diameter are expected to be very reactive,
not only because of the large surface area but also as a result of
the significantly different electronic structure of the small
nanoclusters [4,5].
Among the various preparative methods [1], Metal Vapour
Synthesis (MVS) provides a valuable synthetic route to very
active and selective nanostructured catalysts [6–8]. Solvent-
stabilized metal microclusters (solvated metal atoms, SMA),
obtained by co-condensation of metal vapours with weakly
* Corresponding author. Tel.: +39 050 2219224; fax: +39 050 2219260.
E-mail address: [email protected] (P. Pertici).1 Present address: Drogheria e Alimentari S.r.l., via Nilde Iotti 23, 53037
Firenze, Italy.
0926-860X/$ – see front matter # 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.apcata.2008.01.010
stabilizing organic ligands, are good precursors for the
preparation of very efficient catalysts, which are employed in
a wide range of reactions such as oligomerization [9,10],
hydroformylation [11], hydrosilylation [12,13], silylformylation
[14] and carbon–carbon coupling [15,16]. We recently reported
that nanosized rhodium catalysts supported on g-alumina,
prepared by deposition of rhodium particles from mesitylene-
solvated rhodium atoms stabilized by the added ligand
trioctylamine (TOA), are excellent hydrogenation catalysts
[17]. The trioctylamine (TOA) serves to quench the growth of
the metal microclusters in the mesitylene solution [18].
Encouraged by these preliminary results, we have studied the
catalytic activity of these systems for selective hydrogenation
of the a,b-unsaturated ketones 4-(60-methoxy-20-naphthyl)-3-
buten-2-one, 1, and 2-acetyl-5,8-dimethoxy-3,4-dihydro-
naphthalene, 2, to the corresponding saturated ketones. These
compounds are of interest to pharmaceutical industry. The
catalytic activity has been compared with that of catalysts
similarly prepared in the absence of TOA and with that of
commercial samples of rhodium on g-alumina. Complexing
C. Evangelisti et al. / Applied Catalysis A: General 339 (2008) 84–92 85
properties of TOA were investigated by 1H NMR DOSY
(Diffusion Ordered Spectroscopy) analysis.
2. Experimental
2.1. General
All operations involving the MVS products were performed
under a dry argon atmosphere. The co-condensation of rhodium
and mesitylene was carried out in a static reactor previously
described [19]. The ‘‘mesitylene-solvated Rh atoms’’ solution
was worked up under argon atmosphere with use of the standard
Schlenk techniques. The amount of rhodium in the above
solution was determined by Atomic Absorption Spectrometry
in a electrochemically heated graphite furnace with a
PerkinElmer 4100ZL instrument. The limit of detection
calculated for rhodium was 2 ppb. Solvents were purified by
conventional methods, distilled and stored under argon.
Commercial g-Al2O3 (Chimet product, type 49, surface area
110 m2/g, mean particle diameter 31 mm) was dried in a static
oven before use. Commercial rhodium on g-Al2O3 (5 wt.% of
Rh, surface area 130 m2/g) was an Engelhardt product.
Trioctylamine (from Aldrich) was distilled and stored over
KOH pellets before use. 4-(60-Methoxy-2,-naphthyl)-3-buten-
2-one, 1, was prepared starting from 2-bromo-6-methoxy-
naphthalene (Aldrich product) according to the procedure
described in the literature [20]. 2-Acetyl-5,8-dimethoxy-3,4-
dihydronaphthalene, 2, was prepared by starting from
p-benzoquinone and 1,3-butadiene, methylation with dimethyl-
sulfate, isomerization with potassium t-butoxide and acylation,
according to the procedure reported in the literature [21,22].
The GLC analyses were performed on a PerkinElmer Auto
System gas chromatograph, equipped with a flame ionization
detector (FID), using a SiO2 column (DB1, 30 m � 0.52 mm,
5 mm) and helium as carrier gas. The TLC analyses were
performed with silica gel using petroleum ether/AcOEt 8/2 as
eluent. The HPLC analyses were performed on a Waters 600E
chromatograph, equipped with a Lichrosper 100 column (RP
18, 250 mm � 40 mm, 5 mm) using CH3CN/TFA 0.1% 60/40
as eluent with a flow of 1 ml/min at l = 214 nm. The GC–MS
analyses were carried out with a PerkinElmer Q-mass 910
spectrometer connected with a PerkinElmer gas chromato-
graph, equipped with a ‘‘split–splitless’’ injector, using a SiO2
capillary column and helium as carrier gas. 1H NMR and 13C
NMR spectra were measured on a Varian Gemini 200
spectrometer at 200 and 50 MHz, respectively, using chloro-
form-d as a solvent; chemical shifts are relative to internal
Si(CH3)4. NMR measurements were also performed on a
Varian INOVA 600 spectrometer operating at 600 and 150 MHz
for 1H and 13C, respectively, using a 5 mm broadband inverse
probe with z-axis gradient. The sample temperature was
maintained at 25 8C. 1H and 13C NMR chemical shifts are
referenced to TMS as external standard. The 2D NMR spectra
were obtained by using standard sequences. Proton gCOSY 2D
spectra were recorded in the absolute mode acquiring 4 scans
with a 3 s relaxation delay between acquisitions for each of 256
FIDs. DOSY experiments were performed on samples obtained
by evaporation of the solvent from the Rh(TOA)/mesitylene
solvated and further dissolution in C6D6. They were carried out
by using a stimulated echo sequence with self-compensating
gradient schemes, a spectral width of 6600 Hz and 64 K data
points. A value of 120 ms was used for D, 1.0 ms for d, and g
was varied in 30 steps (16 transients each) to obtain an
approximately 90–95% decrease in the resonance intensity at
the largest gradient amplitudes. The baselines of all arrayed
spectra were corrected prior to processing the data. After data
acquisition, each FID was apodized with 1.0 Hz line broad-
ening and Fourier transformed. The data were processed with
the DOSY macro (involving the determination of the resonance
heights of all the signals above a pre-established threshold and
the fitting of the decay curve for each resonance to a Gaussian
function) to obtain pseudo two-dimensional spectra with NMR
chemical shifts along one axis and calculated diffusion
coefficients along the other. Infrared (IR) spectra were recorded
using a PerkinElmer Spectrum GX Ft-IR. The melting points
were determined on a Reichert Thermovar instrument.
2.2. Preparation of the rhodium catalysts
2.2.1. Synthesis of the solvated Rh atoms
In a typical experiment, rhodium vapour, generated by
resistive heating of a tungsten wire surface coated with
electrodeposited rhodium (170 mg), was co-condensed at
liquid nitrogen temperature with mesitylene (45 ml) in the
glass reactor chamber of the MVS apparatus in ca. 45 min. The
reactor chamber was warmed to the melting point of the solid
matrix (ca. �30/�40 8C) and the resulting brown solution was
siphoned at low temperature in a Schlenk tube and kept in a
refrigerator at �20 8C. The content of the metal solution was
1.8 mg rhodium/ml (0.0175 mg atom/ml).
2.2.2. Preparation of rhodium on g-Al2O3 catalysts
The Rh/mesitylene reaction solution (5.6 ml, 10 mg Rh) was
added to a suspension of g-Al2O3 (10 g) in mesitylene (25 ml).
The mixture was stirred for 12 h at room temperature. The
colourless solution was removed and the light-brown solid,
containing 0.1 wt.% Rh, was washed with n-pentane and dried
under reduced pressure. The Rh/g-Al2O3 catalysts, containing
1 wt.% Rh, was prepared similarly using 1 g of g-Al2O3.
2.2.3. Preparation of rhodium–trioctylamine (TOA)
on g-Al2O3 catalysts
(a) Preparation of Rh(TOA)/mesitylene solution. Trioctylamine
(TOA) (0.56 ml, 1.31 mmol) was added to the MVS Rh/
mesitylene solution (25 ml, 0.44 mg atom) and the mixture
was stirred for 1 h at room temperature. The resulting
brown Rh(TOA)/mesitylene solution was stable at room
temperature for a long time (about 3 months).
(b) P
reparation of the Rh(TOA)/g-Al2O3 catalysts. The brownRh(TOA)/mesitylene solution (5.6 ml, 10 mg Rh) was
added to a suspension of g-Al2O3 (10 g) in mesitylene
(25 ml). The mixture was stirred for 12 h at room
temperature. The colourless mesitylene was removed and
the light-brown solid, containing 0.1 wt.% Rh, was washed
Tabl
Hyd
hydr
Run
1
2
3d
4
5
6
7
8e
9g
Reaa Db Sc Md Re Rf Rg R
C. Evangelisti et al. / Applied Catalysis A: General 339 (2008) 84–9286
with pentane and dried under reduced pressure. The
Rh(TOA)/g-Al2O3 catalyst containing 1 wt.% Rh was
prepared similarly using 1 g of g-Al2O3.
2.3. Catalytic reactions
2.3.1. Hydrogenation of 4-(60-methoxy-2,-naphthyl)-3-
buten-2-one, 1, to 4-(60-methoxy-20-naphthyl)-butan-2-one,
1a, NabumetoneTM
In a typical experiment (runs 1–7), toluene (20 ml), 4-(6,-
methoxy-2,-naphthyl)-3-buten-2-one, 1 (1 g, 4.42 mmol) and
the rhodium catalyst (4.42 � 10�3 mg atom Rh) were intro-
duced under nitrogen atmosphere into a 100 ml flat-bottomed,
three necked flask equipped with a stirring magnetic bar, a
silicon stopper and connected to a gas-volumetric burette
containing hydrogen. The nitrogen was removed under vacuum
and hydrogen was introduced. The mixture was stirred (ca.
1200 rev/min) at room temperature and under atmospheric
pressure of hydrogen. The progress of the reaction was
monitored by the absorption of hydrogen in the burette and the
composition of the reaction mixture was determined by GLC
analysis of liquid samples taken from the stoppered side neck
with a syringe. The products were identified by comparison of
their GLC retention times with those of authentic samples and
by GC–MS analysis. The reaction was interrupted at the time
indicated in Table 2.
The runs 8 and 9, performed with a large amount of 1 in
toluene or ethanol 95% as reaction medium, respectively, have
been carried out introducing the solvent (100 ml), 1 (50 g,
0.221 mol) and the catalyst [Rh(TOA)/g-Al2O3 (0.1 wt.% Rh),
22.7 g, 0.221 � 10�3 g atom Rh] in a 1l flat-bottomed, three
necked flask equipped with a stirring magnetic bar, a silicon
stopper and a glass cannula, connected to the hydrogen
reservoir, for the gas bubbling. The nitrogen was removed
under vacuum and hydrogen was introduced. The mixture was
stirred (ca. 1200 rev/min) at room temperature and hydrogen
e 1
rogenation of 4-(60-methoxy-20-naphthyl)-3-buten-2-one, 1, with MVS-rhodium
ogen
Catalyst Time (min)
Rh/g-Al2O3 (1 wt.% Rh) 120
Rh(TOA)/g-Al2O3 (1 wt.% Rh) 42
Rh/g-Al2O3 commercial (5 wt.% Rh) 720
Rh(TOA)/g-Al2O3 (0.1 wt.% Rh) 24
Rh/g-Al2O3 (0.1 wt.% Rh) 180
Rh(TOA)/g-Al2O3 (1 wt.% Rh) recovered from run 2 42
Rh(TOA)/g-Al2O3 (0.1 wt.% Rh) recovered from run 4 24
Rh(TOA)/g-Al2O3 (0.1 wt.% Rh) 24
Rh(TOA)/g-Al2O3 (0.1 wt.% Rh) 18
ction conditions: compound 1 = 1 g (4.42 mmol); catalyst [Rh] = 4.42 � 10�3
etermined by GLC analysis.
ee Scheme 2 for the assignment of the products.
oles of converted 1 per gram atom rhodium per minute.
eaction performed with a molar ratio 1/Rh = 100.
eaction performed with: 1 = 50 g (0.221 mol); catalyst = 22.7 g (0.1 wt.% Rh
ecovered by crystallization.
eaction performed with: 1 = 50 g (0.221 mol); catalyst = 22.7 g (0.1 wt.% Rh
was bubbled through the suspension. The progress of the
reaction was monitored as above reported. At complete
conversion of 1 the reaction was stopped (see Table 1). The
solution was filtered and the catalyst was washed with the
reaction solvent. The solutions were united and the solvent was
removed in vacuo giving a crude solid which was recrystallized
from methanol to give pure 1a (49.5 g, 0.216 mol, yield 98%).
mp = 81–83 8C. MS m/z: 228 (M+). IR n(C O) = 1705 cm�1.1H NMR, d: 2.17 (s, 3H, CH3CO); 2.85 (t, 2H, J = 7.2 Hz,
ArCH2CH2); 3.05 (t, 2H, CH2CH2CO); 3.93 (s, 3H, CH3O);
7.11–7.75 (m, 6H, H arom). 13C NMR, d: 198.1 (CO); 151.1
(Ar); 136.2 (Ar); 133.1 (Ar); 128.9 (Ar); 128.4 (Ar); 127 (Ar);
126.3 (Ar); 125.1 (Ar), 118.9 (Ar); 105.7 (Ar); 55.4 (OMe);
45.3 (CH2CO); 32.7 (CH2Ar); 30.3 (COCH3).
2.3.2. Hydrogenation of 2-acetyl-5,8-dimethoxy-3,4-
dihydronaphthalene, 2, to 2-acetyl-5,8-dimethoxy-1,2,3,4-
tetrahydronaphthalene, 2aIn a typical experiment (runs 10–15), toluene (20 ml),
2-acetyl-5,8-dimethoxy-3,4-dihydronaphthalene, 2 (1 g,
4.3 mmol) and the rhodium catalyst (4.3 � 10�2 mg atom
Rh) were introduced under nitrogen atmosphere into a 100 ml
flat-bottomed, three necked flask equipped with a stirring
magnetic bar, a silicon stopper and connected to a gas-
volumetric burette containing hydrogen. The nitrogen was
removed under vacuum and hydrogen was introduced. The
mixture was stirred (ca. 1200 rev/min) at room temperature and
under atmospheric pressure of hydrogen. The progress of
the reaction was monitored by the absorption of hydrogen in the
burette and by TLC analysis of liquid samples taken from
the stoppered side neck with a syringe. The composition of the
reaction mixture was determined by HPLC analysis by
comparing the retention times with those of authentic samples.
The reaction was interrupted at the time indicated in Table 1.
The runs 16 and 17, performed with a large amount of 2 in
toluene or ethanol 95% as reaction medium, respectively, have
on g-alumina derived catalysts at room temperature and atmospheric pressure of
Conversiona (%) Selectivity (%)a,b Specific activityc (SA) (min�1)
1a 1b 1c
100 98 – 2 8.3
100 100 – – 23.8
100 90 – 10 0.3
100 100 – – 41.7
10 100 – – 0.6
100 100 – – 23.8
100 100 – – 41.7
100 100 (98)f – – 41.7
100 100 (98)f – – 55.6
mg atoms; solvent = toluene (20 ml); T = 25 8C; P(H2) = 1 atm.
, 0.221 � 10�3 g atoms); solvent = toluene (100 ml).
, 0.221 � 10�3 g atoms) solvent = ethanol 95% (100 ml).
Table 2
Hydrogenation of 2-acetyl-5,8-dimethoxy-3,4-dihydronaphthalene, 2, with MVS-rhodium on g-alumina derived catalysts at room temperature and atmospheric
pressure of hydrogen
Run Catalyst Time (h) Conversiona (%) Selectivity (%)a,b Specific activityc (SA) (h�1)
2a 2b 2c
10 Rh/g-Al2O3 (1 wt.% Rh) 24 100 81 8 11 4.1
11 Rh(TOA)/g-Al2O3 (1 wt.% Rh) 24 100 86 3 11 4.1
12 Rh/g-Al2O3 commercial (5 wt.% Rh) 24 85 74 16 10 3.5
13 Rh(TOA)/g-Al2O3 (0.1 wt.% Rh) 3.5 98 89 3 8 19.6
5 100 90 2 8 20
14 Rh/g-Al2O3 (0.1 wt.% Rh) 5 Traces –
15 Rh(TOA)/g-Al2O3 (0.1 wt.% Rh) recovered from run 13 5 100 90 2 8 20
16d Rh(TOA)/g-Al2O3 (0.1 wt.% Rh) 5 100 90 (84)e 2 8 20
17f Rh(TOA)/g-Al2O3 (0.1 wt.% Rh) 2.5 100 85 (80)e 5 10 40
Reaction conditions: compound 2 = 1 g (4.3 mmol); catalyst [Rh] = 4.3 � 10�2 mg atoms; solvent = toluene (20 ml); T = 25 8C; P(H2) = 1 atm.a Determined by TLC and HPLC analyses.b See Scheme 6 for the assignment of the products.c Moles of converted 2 per gram atom rhodium per hour.d Reaction performed with: 2 = 40 g (0.172 mol); catalyst = 177 g (0.1 wt.% Rh, 0.172 � 10�2 g atoms); solvent = toluene (300 ml).e Recovered by crystallization.f Reaction performed with: 2 = 40 g (0.172 mol); catalyst = 177 g (0.1 wt.% Rh, 0.172 � 10�2 g atoms); solvent = ethanol 95% (300 ml).
C. Evangelisti et al. / Applied Catalysis A: General 339 (2008) 84–92 87
been carried out introducing the solvent (300 ml), 2 (40 g,
0.172 mol) and the catalyst [Rh(TOA)/g-Al2O3 (0.1 wt.% Rh),
177 g, 0.172 � 10�2 g atom Rh] in a 1l flat-bottomed, three
necked flask equipped with a stirring magnetic bar, a silicon
stopper and a glass cannula, connected to the hydrogen
reservoir, for the gas bubbling. The nitrogen was removed
under vacuum and hydrogen was introduced. The mixture was
stirred (ca. 1200 rev/min) at room temperature and hydrogen
was bubbled through the suspension. The progress of the
reaction was monitored as above reported. At complete
conversion of 2 the reaction was stopped (see Table 2). The
solution was filtered and the catalyst was washed with the
reaction solvent. The solutions were collected and the solvent
was removed in vacuo giving a crude product which was
recrystallized from isopropyl alcohol to give pure 2-acetyl-5,8-
dimethoxy-1,2,3,4-tetrahydronaphthalene, 2a (yield = 80–
84%, see Table 2). mp = 81–83 8C. MS m/z: 234 (M+). IR
n(C O) = 1708 cm�1. 1H NMR (600 MHz, CDCl3, 25 8C): d
1.63 (m, 1H, H-d), 2.16 (m, 1H, H-d0), 2.25 (s, 3H, COMe), 2.54
(ddd, J = 17.3, 11.7, 5.9 Hz, 1H, H-e), 2.59 (ddd, J = 16.6, 11.6,
1.5 Hz, 1H, H-b), 2.65 (m, 1H, H-c), 2.94 (ddd, J = 17.3, 5.4,
3.0 Hz, 1H, H-e0), 3.04 (ddd, J = 16.6, 4.6, 1.8 Hz, 1H, H-b0),3.77 (s, 3H, OMe), 3.78 (s, 3H, OMe), 6.63 (s, 2H, H-a). 13C
NMR (150 MHz, CDCl3, 25 8C): d 211.5 (CO), 151.3
(quaternary C), 151.2 (quaternary C), 126.2 (quaternary C),
125.4 (quaternary C), 106.9 (CH–Ar), 106.8 (CH–Ar), 55.6
(OMe), 47.3 (CH), 28.1 (Me), 25.4 (CH2), 24.4 (CH2), 23.1
(CH2).
3. Results and discussion
3.1. Preparation of the catalysts: (i) rhodium on
g-alumina, Rh/g-Al2O3, and (ii) rhodium, containing
trioctylamine (TOA), on g-alumina, Rh(TOA)/g-Al2O3
The catalysts containing rhodium on g-alumina, Rh/g-
Al2O3, and Rh(TOA)/g-Al2O3, were prepared by MVS, as
shown in Scheme 1.
The solution of mesitylene-solvated Rh atoms (Scheme 1,
solvated A), obtained from rhodium and mesitylene vapours,
is stable at low temperature (�40 8C). On warming to room
temperature in the presence of g-Al2O3, it furnishes metal
nanoparticles which deposit homogeneously on the support
with formation of the Rh/g-Al2O3 catalyst. Addition of the
organic ligand trioctylamine, TOA, to solvated A stabilizes
the microclusters against agglomeration, giving rise to a
solution of mesitylene-solvated Rh atoms which is stable at
r.t. (Scheme 1, solvated B). On addition of g-Al2O3 to
solvated B, rhodium nanoparticles, containing TOA, deposit
homogeneously on the support with formation of the
Rh(TOA)/g-Al2O3 catalyst.
The rhodium particle size distribution, determined by
HRTEM analyses [17], gave a mean diameter dm = 2.1
� 0.25 nm for the Rh/g-Al2O3 catalyst and a mean diameter
dm = 1.1 � 0.25 nm for the Rh(TOA)/g-Al2O3 catalyst. The
structural characterization of Rh(TOA)/g-Al2O3 catalyst,
performed by HRTEM and EXAFS analyses and by IR
spectroscopy, after treatment with CO, demonstrated the
presence of homogeneously distributed metal particles with
very small diameters (about 1.1 nm). The effect of TOA was to
prevent the aggregation of atoms/clusters to form large particles
thus making available more Rh atoms for the catalysis. In
addition, TOA stabilizes the nanoparticles towards poisoning
and hinders their extensive oxidation by the solid oxide support
Fig. 1. DOSY map (600 MHz, C6D6, 25 8C) of solvated Rh(TOA)/mesitylene.
Scheme 1.
C. Evangelisti et al. / Applied Catalysis A: General 339 (2008) 84–9288
[17]. All these factors account for the high activity exhibited by
the Rh(TOA)/g-Al2O3 catalysts.
3.2. Characterization via 1HNMR and 1HNMR-DOSY of
mesitylene-solvated rhodium atoms solution stabilized by
TOA (solvated B, Scheme 1)
DOSY technique represents a very powerful tool for the
detection of size-dependent phenomena [23,24]. As a matter of
fact, it allows to measure translational diffusion coefficients
(D), which are correlated to molecular sizes by means of
hydrodynamic radius (RH) on the basis of Stokes-Einstein
equation (Eq. (1)):
D ¼ kT
6ph R H
(1)
where k is the Boltzmann constant, h is the solvent viscosity and
T is the temperature in K. Eq. (1) strictly holds for spherical
systems in non-viscous solutions, whose viscosity can be
approximated to that one of the solvent. Thus we recorded
DOSY maps of pure TOA in C6D6 and of its rhodium solvated
system. For the pure compound we measured a diffusion
coefficient of 7.0 � 10�10 m2 s�1 to be compared to the value
of 5.9 � 10�10 m2 s�1 (Fig. 1) corresponding to the solvated
species, the diameter of which was calculated as about 1.1 nm
(Eq. (1)). A remarkable decrease of the amine diffusion coeffi-
cient occurred as a consequence of metal complexation.
The diameter of the solvated species in solution is
comparable to that found by HRTEM analysis of the
Rh(TOA)/g-Al2O3 sample [17] reported in Section 3.1,
pointing out that no aggregation process of the nanoparticles
happens during their deposition on the support.
Interestingly, the comparison of 1H NMR spectra in C6D6 of
the pure amine and of the solvated species solution (Fig. 2a and
b, respectively) pointed out differences both in the linewidth
and chemical shifts, these last being mainly relevant for b- and
g-methylene groups of the amine, low-frequency shifted by
�0.025 and �0.055 ppm, respectively, These results are in
agreement to those reported by Richard and co-workers [25]
regarding colloidal Rh(TOA) systems obtained from reduction
of RhCl3, in which amine aliphatic chains are mainly involved
in the formation of metal aggregates. They highlighted a
dynamic interaction between the doublet of the amine nitrogen
and the surface of the rhodium particle. This interaction gives
rise to a spatial distribution of the aliphatic chains in which the
a-CH2 groups are far from the metal surface while the b-CH2
and the g-CH2 groups are located near to this surface, justifying
their chemical shifts with respect to the free amine.
3.3. Catalytic studies with Rh/g-Al2O3 and
Rh(TOA)/g-Al2O3 systems
3.3.1. Selective hydrogenation of the a,b-unsaturated
ketones 4-(60-methoxy-20-naphthyl)-3-buten-2-one, 1, and
2-acetyl-5,8-dimethoxy-3,4-dihydronaphthalene, 2, to the
corresponding saturated ketones 4-(60-methoxy-20-naphthyl)-butan-2-one, 1a, and 2-acetyl-5,8-dimethoxy-
1,2,3,4-tetrahydronaphthalene, 2aConsidering the interesting catalytic properties of Rh/g-
Al2O3 and of Rh(TOA)/g-Al2O3 exhibited in the selective
hydrogenation of cinnamaldehyde to give the hydrocinnamal-
dehyde in high yield [17], these catalysts have been employed
in the selective reduction of the double bond in a,b-unsaturated
ketones such as 4-(60-methoxy-20-naphthyl)-3-buten-2-one, 1,
and 2-acetyl-5,8-dimethoxy-3,4-dihydronaphthalene, 2, which
Fig. 2. 1H NMR (600 MHz, C6D6, 25 8C) spectra of (a) trioctylamine, TOA and
(b) solvated Rh(TOA)/mesitylene.
C. Evangelisti et al. / Applied Catalysis A: General 339 (2008) 84–92 89
are precursors to compounds of considerable value in fine
chemistry.
3.3.1.1. Hydrogenation of 4-(6,-methoxy-2,-naphthyl)-3-bu-
ten-2-one, 1. The 4-(60-methoxy-20-naphthyl)-3-buten-2-one,
1, furnishes by hydrogenation of the double bond the saturated
ketone 4-(60-methoxy-20-naphthyl)-butan-2-one, 1a, commer-
cially called nabumetoneTM, which is an important non-
steroidal anti-inflammatory drug. Other products which can be
obtained in the course of the hydrogenation of 1 are the a,b-
unsaturated alcohol, 1b, and the saturated alcohol, 1c
(Scheme 2).
The formation of 1a by the catalytic hydrogenation of 1 is
the final step of a synthetic procedure industrially used for the
preparation of nabumetone. Such procedure starts from 2-
bromo-6-methoxynaphthalene and, via the reaction between 6-
methoxy-2-naphthalenecarbaldehyde and acetone, furnishes 1
in 50% yield [20,26]. By catalytic hydrogenation of 1 in the
Scheme
Scheme
presence of 10% Pd on carbon at room temperature and
atmospheric pressure of hydrogen 1a is obtained in 70% yield
(Scheme 3).
Compound 1 is obtained also in high yield (90%) but under
severe reaction conditions (autoclave, 130 8C) by the palla-
dium-catalyzed C–C coupling of 2-bromo-6-methoxynaphtha-
lene and 3-buten-2-one, according to the methodology of the
Heck–Mizoroki reaction (Scheme 4) [27].
Recent publications describe improved methods in the
preparation of 1a by hydrogenation of 1. A patent [28] reports
that rhodium-based catalytic systems heterogenized on an
organic or mineral support, prepared by reduction of Rh(III)
salts with hydrogen in the presence of lipophilic tertiary
amines, tertiary amides or quaternary ammonium salts, resulted
very efficient in the selective reduction of 1 to 1a (yield � 98%,
hydrogen pressure 5–15 atm, T = 50–75 8C). Ravasio et al. [29]
report that copper on silica catalysts, prepared by reduction of
Cu(II) salts with hydrogen at 270 8C, give 1a by hydrogenation
of 1 in high yield (98%, hydrogen pressure 5 atm, T = 90 8C).
The results obtained in the hydrogenation of 1 with the
catalysts Rh/g-Al2O3 and Rh(TOA)/g-Al2O3 prepared by MVS
are reported in Table 1. The reactions were performed under
mild conditions (room temperature, atmospheric pressure of
hydrogen) using a molar ratio substrate/Rh = 1000.
The Rh/g-Al2O3 (1 wt.% Rh) catalyst showed high activity
and selectivity in the reduction of 1 to 1a (run 1,
SA = 8.3 min�1, sel. = 98%). Even better results were obtained
with the Rh(TOA)/g-Al2O3 (1 wt.% Rh) catalyst, which
reduces 1 completely to 1a with high catalytic activity (run
2, SA = 23.8 min�1, sel. = 100%). In contrast, the commercial
catalyst showed a lower activity and a lower selectivity than
the previous reported catalysts (run 3, SA = 0.3 min�1,
sel. = 90%). The MVS-derived catalyst with a low rhodium
loading, Rh(TOA)/g-Al2O3 (0.1 wt.% Rh), exhibited the best
2.
3.
Scheme 4.
C. Evangelisti et al. / Applied Catalysis A: General 339 (2008) 84–9290
catalytic properties, reducing completely 1 to 1a with a very
high efficiency (run 4, SA = 41.7 min�1, sel. = 100%). The Rh/
g-Al2O3 (0.1 wt.% Rh) catalyst containing no TOA furnished
complete selectivity in 1a but displayed low activity (run 5,
SA = 0.6 min�1, sel. = 100%). It is worth noting that, as far as
the activity of the catalysts having a low rhodium loading is
concerned, a similar result has been previously observed also in
the hydrogenation of cinnamaldehyde [17]. No evidence of
catalytic deactivation was found for Rh(TOA)/g-Al2O3
catalysts containing either 1 wt.% Rh or 0.1 wt.% Rh. Such
catalysts, recovered from the runs 2 and 4, respectively, and
reused, showed the same catalytic activity (runs 6 and 7).
Because of the high efficiency shown by Rh(TOA)/g-Al2O3
(0.1 wt.% Rh) catalyst in the hydrogenation of 1 to 1a, the
process was scaled to 50 g, under the experimental conditions
of run 4; the yield of 1a was the same (run 8). Excellent results
were also obtained in the environmentally friendly solvent 95%
ethanol; conversion to 1a was complete and the reaction was
faster than in toluene (run 9, SA = 55.6 min�1, sel. = 100%).
No leaching of rhodium from the catalyst to the solution was
observed in the runs 8 and 9. In fact, the recovered catalyst
maintains the same catalytic activity and it contains 0.1 wt.%
Rh, as in the starting material, within the interval �2%. The
behaviour of the mother liquor was also investigated. First,
AAS revealed no rhodium content. In addition, as a further test
for the presence of active metal in the recovered solution, no
hydrogenation was observed adding fresh 1 for up to 24 h.
Finally, AAS revealed no rhodium content in 1a.
Scheme
The mild reaction conditions (room temperature, atmo-
spheric pressure of hydrogen), the complete selectivity to
NabumetoneTM, the stability of the Metal Vapour Synthesis-
derived Rh(TOA)/g-Al2O3, 0.1 wt.% Rh, make this catalyst an
useful alternative to the very active catalysts recently reported
[28,29].
3.3.1.2. Hydrogenation of 2-acetyl-5,8-dimethoxy-3,4-dihy-
dronaphthalene, 2. The interest in the selective reduction of
the double bond in the 2-acetyl-5,8-dimethoxy-3,4-dihydro-
naphthalene, 2, is related to the importance of the corresponding
saturated carbonyl compound 2-acetyl-5,8-dimethoxy-1,2,3,4-
tetrahydronaphthalene, 2a, in fine chemistry. In fact 2a is a
precursor of the so-called ‘‘Wong’s tetraline’’ [30], 3, which is
the main building block of antitumor anthracyclinic compounds,
4, currently produced by pharmaceutical industries (Scheme 5)
[31,32].
The compounds which can be formed in the hydrogenation
of 2 are, in addition to the saturated ketone 2a, the a,b-
unsaturated alcohol, 2b, and the saturated alcohol, 2c
(Scheme 6).
The results obtained in the hydrogenation of 2 with the
catalysts Rh/g-Al2O3 and Rh(TOA)/g-Al2O3 prepared by MVS
are reported in Table 2. The reactions were performed at room
temperature and atmospheric pressure of hydrogen, using a
molar ratio substrate/Rh = 100.
In the presence of the Rh/g-Al2O3 catalyst (1 wt.% Rh), the
conversion of 2 is complete in 24 h with high selectivity in 2a
5.
Scheme 6.
C. Evangelisti et al. / Applied Catalysis A: General 339 (2008) 84–92 91
(run 10, SA = 4.1 h�1, sel. = 81%). Similar results were obtained
with the Rh(TOA)/g-Al2O3 catalyst (1 wt.% Rh) (run 11,
SA = 4.1 h�1, sel. = 86%). The commercial catalyst Rh/g-Al2O3
(5 wt.% Rh) is less active and less selective to 2a than the MVS-
derived Rh catalysts (run 12, SA = 3.5 h�1, sel. = 74%). A very
high catalytic activity and selectivity to 2a was obtained using the
Rh(TOA)/g-Al2O3 (0.1 wt.% Rh) catalyst having a low rhodium
loading (run 13, SA = 20 h�1, sel. = 90%), as previously
observed in the hydrogenation of 4-(60-methoxy-20-naphthyl)-
3-buten-2-one, 1. Under the same conditions the Rh/g-Al2O3
(0.1 wt.% Rh) exhibits a very low catalytic activity (run 14). The
stability of the most active Rh(TOA)/g-Al2O3 catalyst (0.1 wt.%
Rh) was confirmed using the material recovered from run 13
which showed the same catalytic activity as that of the starting
material (run 15). With this catalyst, identical results in terms of
kinetics and selectivity were obtained when the amounts of 2
were increased to 40 g (run 16, SA = 20 h�1, sel. = 90%). In the
environmental friendly solvent 95% ethanol the catalyst is more
active but somewhat less selective than in toluene (run 17,
SA = 40 h�1, sel. = 85%). 2a was obtained pure from runs 16 and
17 very easily by crystallization of the residue from isopropyl
alcohol, following the detailed procedure described in the
experimental section. No leaching of rhodium from the catalyst
to the solution was observed in the runs 16 and 17 as proved
performing the tests and the AAS measurements foregoing
reported in Section 3.3.1.1.
4. Conclusions
It appears from the reported data that the Rh(TOA)/g-Al2O3
samples obtained by MVS are valuable catalysts for the
selective hydrogenation of the a,b-unsaturated ketones 4-(60-methoxy-20-naphthyl)-3-buten-2-one, 1, and 2-acetyl-5,8-
dimethoxy-3,4-dihydronaphthalene, 2, to the corresponding
saturated ketones 4-(60-methoxy-20-naphthyl)-butan-2-one, 1a
(NabumetoneTM) and 2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahy-
dronaphthalene, 2a, respectively, which are compounds of
considerable value in fine chemistry.
The Rh(TOA)/g-Al2O3 samples are more convenient than
catalysts similarly prepared in the absence of TOA and they are
considerably more active than analogous commercial samples.
The role of TOA, which is crucial in the generation of these
very active catalysts, is to prevent aggregation of the rhodium
particles in the mesitylene-solvated rhodium solutions. As
indicated by DOSY-NMR analysis, the hydrodynamic diameter
of the TOA-stabilized rhodium particles is very small, about
1.1 nm including the shell of the stabilizer. It accounts for the
presence on the g-alumina of rhodium nanoparticles of
comparable size, still containing the TOA stabilizer, surround-
ing the metal particles [17]. The presence of TOA allows these
catalysts to be very active even at low rhodium loading
(0.1 wt.% Rh), the NR3 molecule protecting the rhodium atoms
from oxidation by the solid oxide support. Under the same
reaction conditions Rh/g-Al2O3 samples prepared in absence of
TOA and containing 0.1 wt.% Rh are quite inactive.
The fact that aliphatic amines bearing large alkyl groups
bind to transition metal atoms and thereby enhance the catalytic
activity of these atoms in the catalytic hydrogenation of olefins
was observed some years ago by Frolov [33]. The results here
reported are an additional example of the potential of these
systems as hydrogenation catalysts, which can be regarded as
new-generation hydrogenation catalysts.
Acknowledgements
We thank the Consiglio Nazionale delle Ricerche (CNR) for
financial support of this research. FB and GUB wish to thank
Ministero dell’Universita e Ricerca (MUR, grant 2005037725),
for financial support of the NMR experiments. The authors thank
Dr. Emanuela Pitzalis (IPCF-CNR, Pisa, Italy) for AAS analyses.
References
[1] B. Ziou, S. Hermans, G.A. Somorjai (Eds.), Nanotechnology in Catalysis,
Springer, New York, 2004.
[2] B.A. Roucoux, J. Schultz, H. Patin, Chem. Rev. 102 (2002) 3757–3778.
[3] G. Schmid, L.F. Chi, Adv. Mater. 10 (1998) 515–526.
[4] C.N.R. Rao, G.U. Kulkarni, P.J. Thomas, P.P. Edwards, Chem. Eur. J. 8
(2002) 28–35.
[5] W.A. de Heer, Rev. Modern Phys. 65 (1993) 611–676.
[6] G. Vitulli, C. Evangelisti, A.M. Caporusso, P. Pertici, N. Panziera, S.
Bertozzi, P. Salvadori, in: B. Corain, G. Schmid, N. Toshima (Eds.), Metal
Nanoclusters in Catalysis and Materials Science: The Issue of Size-
Control, Elsevier, Amsterdam, 2007, Chapter 32.
[7] G. Vitulli, P. Pertici, S. Bertozzi, A.M. Caporusso, R. Lazzaroni, P.
Salvadori, in: W.A. Herrmann (Ed.), Synthetic Methods of Organome-
tallics and Inorganics Chemistry: Catalysis, vol. 10, Brauer/Herrmann,
Munich, 2002, pp. 64–71.
[8] K.J. Klabunde, Free Atoms, Clusters and Nanoscale Particles, Academic
Press, San Diego, 1994.
[9] A. Colligiani, G. Vitulli, J. Kraus, S. Biagi, P. Salvadori, R. Settambolo, M.
Pasero, J. Mol. Catal. 53 (1989) 133–141.
[10] G. Vitulli, S. Bertozzi, M. Vignali, R. Lazzaroni, P. Salvadori, J. Orga-
nomet. Chem. 326 (1987) C33–C36.
[11] S. Bertozzi, N. Campigli, G. Vitulli, R. Lazzaroni, P. Salvadori, J.
Organomet. Chem. 487 (1995) 41–45.
[12] A.M. Caporusso, N. Panziera, P. Pertici, E. Pitzalis, P. Salvadori, G.
Vitulli, G. Martra, J. Mol. Catal. 150 (1999) 275–285.
[13] C. Polizzi, A.M. Caporusso, G. Vitulli, P. Salvadori, J. Organomet. Chem.
451 (1993) C4–C6.
[14] L.A. Aronica, S. Terreni, A.M. Caporusso, P. Salvadori, Eur. J. Org. Chem.
(2001) 4321–4329.
C. Evangelisti et al. / Applied Catalysis A: General 339 (2008) 84–9292
[15] N. Panziera, P. Pertici, L. Barazzone, A.M. Caporusso, G. Vitulli, P.
Salvadori, S. Borsacchi, M. Geppi, C. Veracini, G. Martra, L. Bertinetti, J.
Catal. 246 (2) (2007) 351–361.
[16] A.M. Caporusso, P. Innocenti, L.A. Aronica, G. Vitulli, R. Gallina, A.
Biffis, M. Zecca, B. Corain, J. Catal. 234 (2005) 1–13.
[17] G. Vitulli, C. Evangelisti, N. Panziera, P. Pertici, A.M. Caporusso, P.
Salvadori, M.G. Faga, C. Manfredotti, G. Martra, S. Coluccia, A. Balerna,
S. Colonna, S. Mobilio, J. Organomet. Chem. 681 (2003) 37–50.
[18] K.S. Nagabhushana, H. Bonnemann, in: B. Zhou, S. Hermans, G.A.
Somorjai (Eds.), Nanotechnology in Catalysis, vol. 1, Springer, New York,
2004, Chapter 4.
[19] G. Vitulli, E. Pitzalis, R. Lazzaroni, P. Pertici, P. Salvadori, O. Salvetti, S.
Coluccia, G. Martra, Mater. Sci. Forum 195 (1995) 93–102.
[20] C. Prabhakar, G. Bakki Reddy, Ch. Maheedhara Reddy, D. Nageshwar, A.
Sivalakshmi Devi, J. Moses Babu, K. Vyas, M.R. Sarma, G. Om Reddy,
Org. Process Res. Develop. 3 (1999) 121–125.
[21] F. Badalassi, P. Crotti, C. Di Bugno, F. D’Arata, L. Favero, A. Ramacciotti,
Tetrahedron: Asym. 12 (2001) 3155–3161.
[22] A.V. Rama Rao, J.S. Yadav, K. Bal Reddy, A.R. Mehendale, Tetrahedron
40 (1984) 4643–4647.
[23] C.S. Johnson Jr., Prog. Nucl. Magn. Reson. Spectrosc. 34 (1999) 203–256.
[24] Magn. Reson. Chem. 40 (2002) Special Issue, NMR and Diffusion, S1-
S152.
[25] T. Yonezawa, T. Tominaga, D. Richard, J. Chem. Soc., Dalton Trans.
(1996) 783–789.
[26] A.C. Goudie, L.M. Gaster, A.W. Lake, C.J. Rose, P.C. Freeman, B.O.
Hughes, D. Miller, J. Med. Chem. 21 (1978) 1260–1264.
[27] M. Aslam, V. Elango, K.G. Davenport, Synthesis: Commun. (1989) 869–
871.
[28] O. Piccolo, A. Verrazzani, Patent, Int. Publ. Number: WO 03/037508 A2
(2003).
[29] N. Ravasio, F. Zaccheria, P. Allegroni, M. Ercoli, Catal. Today 121 (2007)
2–5.
[30] C.M. Wong, R. Schwenk, D. Popien, T.L. Ho, Can. J. Chem. 49 (1971)
2712–2718.
[31] F. Arcamone, L. Bernardi, B. Patelli, A. Di Marco, Gen Offen 2601785;
Chem. Abstr. 85 (1976) 142918j.
[32] F. Arcamone, L. Bernardi, B. Patelli, P. Giardino, A. Di Marco, A.M.
Casazza, C. Soranzo, G. Pratesi, Experientia 34 (1978) 1255–1257.
[33] M.V. Frolov, Platinum Met. Rev. 40 (1996) 8–18.
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