Nanostructured ruthenium on γ-Al2O3 catalysts for the efficient hydrogenation of aromatic compounds

Article abstract of DOI:10.1016/j.jorganchem.2003.11.019

Free and trioctylamine (TOA)-stabilized ruthenium nanoparticles have been prepared by decomposition of the metal precursor Ru(η⁶-cycloocta-1,3,5-triene) (η⁴-cycloocta-1,5-diene) under mild conditions (room temperature, hydrogen atmospheric pressure). The nanoparticles have been deposited on γ-Al₂O₃ supports having different surface area. The resulting systems are active in the hydrogenation of methyl benzoate to methyl cyclohexanoate with a reaction rate decreasing in the order Ru(TOA)/γ-Al₂ O₃ (high surface area, catalyst D)>Ru(TOA)/γ-Al₂ O₃ (catalyst C)>Ru/γ-Al₂O₃ (high surface area, catalyst B) > Ru/γ-Al₂ O₃ (catalyst A). Catalysts A-D are long lived and can be reused without loss of activity; they are considerably more active than a commercial ruthenium on γ-Al₂O₃ sample. High Resolution Transmission Electron Microscopy analyses of such systems show that the nanoparticles are homogeneously dispersed on the support and that the size distribution decreases in the order catalyst A, 2.9 nm > catalyst B, 2.8 nm>catalyst C, 2.4 nm > catalyst D, 2.3 nm. Based on the easy hydrogenation of the aromatic ring to the cyclohexane derivative, an efficient synthesis of 4-carbomethoxyformylcyclohexane, important starting material in the preparation of pharmaceutical products, from the largely available methyl 4-formylbenzoate, has been set up in the presence of catalyst D,

Full text of DOI:10.1016/j.jorganchem.2003.11.019

Journal of Organometallic Chemistry 689 (2004) 639–646
www.elsevier.com/locate/jorganchem
Nanostructured ruthenium on c-Al2O3 catalysts for the
efficient hydrogenation of aromatic compounds
a
a,
a
a
Guido Marconi , Paolo Pertici *, Claudio Evangelisti , Anna Maria Caporusso ,
a
Giovanni Vitulli , Gustavo Capannelli , Manh Hoang , Terence W. Turney
b
c
c
a
Istituto per la Chimica dei Composti Organometallici, ICCOM CNR, Sezione di Pisa, Dipartimento di Chimica e Chimica Industriale,
Universitꢀa di Pisa, via Risorgimento 35, 56126 Pisa, Italy
b
Dipartimento di Chimica e Chimica Industriale, Universitꢀa di Genova, via Dodecaneso 31, 16146 Genova, Italy
CSIRO Manufacturing and Infrastructure Technology, Gate 4 Normandy Road, Clayton Vic. 3168, Australia
c
Received 2 June 2003; accepted 10 November 2003
Abstract
Free and trioctylamine (TOA)-stabilized ruthenium nanoparticles have been prepared by decomposition of the metal precursor
Ru(g6-cycloocta-1,3,5-triene)(g4-cycloocta-1,5-diene) under mild conditions (room temperature, hydrogen atmospheric pressure).
The nanoparticles have been deposited on c-Al2O3 supports having different surface area. The resulting systems are active in the
hydrogenation of methyl benzoate to methyl cyclohexanoate with a reaction rate decreasing in the order Ru(TOA)/c-Al2 O3 (high
surface area, catalyst D) > Ru(TOA)/c-Al2O3 (catalyst C) > Ru/c-Al2O3 (high surface area, catalyst B) > Ru/c-Al2O3 (catalyst A).
Catalysts A–D are long lived and can be reused without loss of activity; they are considerably more active than a commercial
ruthenium on c-Al2O3 sample. High Resolution Transmission Electron Microscopy analyses of such systems show that the
nanoparticles are homogeneously dispersed on the support and that the size distribution decreases in the order catalyst A, 2.9
nm > catalyst B, 2.8 nm > catalyst C, 2.4 nm > catalyst D, 2.3 nm. Based on the easy hydrogenation of the aromatic ring to the
cyclohexane derivative, an efficient synthesis of 4-carbomethoxyformylcyclohexane, important starting material in the preparation
of pharmaceutical products, from the largely available methyl 4-formylbenzoate, has been set up in the presence of catalyst D.
Ó 2003 Elsevier B.V. All rights reserved.
Keywords: Arene hydrogenation; Ruthenium nanoparticles; Trioctylamine; Ruthenium on c-Al2O3 catalysts; HRTEM
1. Introduction
stabilizers, such as organic ligands, surfactants and
polymers. It has been observed that not only the cluster
size, but also the stabilizing ligand can significantly af-
fect the catalytic activity [13,15,18–20]. In this paper, we
report the preparation of Ru/c-Al2O3 systems by de-
position of Ru nanoparticles obtained by the reduction
and displacement of ligands from Ru(g6-COT)(g4-
COD), COT ¼ cycloocta-1,3,5-triene and COD ¼ cyclo-
octa-1,5-diene, [17,21,22], in the absence and in the
presence of trioctylamine as a stabilizer, respectively.
The catalysts were evaluated for the hydrogenation of
monocyclic aromatic compounds such as methyl ben-
zoate and methyl 4-formylbenzoate, an important in-
termediate in fine chemical synthesis [23,24], and their
activity was compared with that of an analogous com-
mercially available catalyst.
The hydrogenation of aromatic compounds, which is
typically performed with heterogeneous catalysts of VIII
group metals, such as rhodium on alumina and Raney
nickel, is still a very important research area in catalysis
[1,2]. Nanosized metal particles, which are expected to
have peculiar properties, different from those of atomic
or molecular species and bulky metal [3,4], are of great
interest in the development of new very efficient and
selective catalytic systems [1,2,5–17]. Metal nanoparti-
cles however are usually generated in the presence of
* Corresponding author. Tel.: ++39-050-2219224; fax: +39-050-
2219260.
E-mail address: pertici@dcci.unipi.it (P. Pertici).
0022-328X/$ - see front matter Ó 2003 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2003.11.019

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G. Marconi et al. / Journal of Organometallic Chemistry 689 (2004) 639–646
2. Experimental
2.1. General considerations
removed under reduced pressure and hydrogen (1 atm)
was introduced. The suspension was stirred at room
temperature until a complete decolourisation was ob-
tained (8 h). The liquid was then removed by decanta-
tion and the Ru on commercial c-Al2O3 was washed
with pentane and dried in vacuo. A final 4.55 g catalyst
containing 3.5 wt% Ru was obtained and hereafter
designated as catalyst A.
Supported 3.5 wt% Ru on high surface area c-Al2O3
(catalyst B) was prepared using the same procedure ex-
cept that c-Al2O3 with a surface area of 340 m2 was used.
All operations involving the use of ruthenium systems
were performed under argon atmosphere using standard
Schlenk techniques. Solvents were purified by standard
methods. The commercial products were degassed and
stored under argon before use. The commercial ruthe-
nium on c-Al2O3 catalyst (5 wt% Ru) was supplied by
Aldrich. The complex Ru(g6-COT)(g4-COD) was ob-
tained as described previously [22]. Commercial c-Al2O3
(Chimet product, surface area SA ¼ 110 m2/g) and high
surface area c-Al2O3 (SA ¼ 340 m2/g) prepared by
thermal decomposition of NH4Al(OH)2CO3 [25], were
used as supports of the ruthenium nanoparticles. The
ruthenium loading on c-Al2O3 supports was determined
by Atomic Absorption Spectrometry using a Perkin–
Elmer 4100ZL instrument at the Istituto per i Processi
Chimico Fisici, CNR, Pisa, Italy. GC analyses were
performed on a Perkin–Elmer 8600 gas chromatograph,
equipped with a flame ionisation detector, using a SiO2
‘‘Wide Bore’’ column (DB1, 30 m ꢀ 0.53 mm, 5 lm) and
helium as carrier gas. GC–MS spectra were recorded on
a Perkin–Elmer Q-mass 910 spectrometer connected
with a Perkin–Elmer gas chromatograph, equipped with
a ‘‘split–splitless’’ injector, using a SiO2 capillary col-
umn and helium as carrier gas. 1H and 13C NMR
spectra were recorded on a Varian Gemini 300 spec-
trometer operating at 300 and 75 MHz, respectively;
chemical shifts are reported relative to internal tetra-
methylsilane. Electron micrographs of the ruthenium on
c-Al2O3 catalysts (3.5 wt% Ru) were obtained with a
JOEL 2010 Microscopy with EDS probe, model Ox-
ford-Link, equipped with a top entry stage. The samples
were ultrasonically dispersed in toluene and then de-
posited on copper grids covered with a holey carbon
film. The metal particle size distribution was obtained by
calculating the average particle diameter (da) of at least
300 particles on the micrograph using the equation,
2.3. Preparation of supported ruthenium on c-Al2O3 in the
presence of trioctylamine as a stabilizer
In a typical experiment, trioctylamine, TOA, (2.1 ml,
4.75 mmol) was added to a yellow solution containing
Ru(g6-COT)(g4-COD) (0.5 g, 1.58 mmol) dissolved in
THF (20 ml). Argon was removed in vacuo and hy-
drogen (1 atm) was introduced. Commercial c-Al2O3
(4.41 g) was then added to the solution and the sus-
pension was stirred overnight at room temperature until
complete decolourisation was obtained. The liquid was
removed by decantation and the resulting supported
Ru(TOA) on commercial c-Al2O3 was washed with
pentane and dried in vacuo. A 4.56 g catalyst containing
3.5 wt% Ru was obtained and hereafter designated as
catalyst C.
The same procedure was used for supported
Ru(TOA) on high surface area c-Al2O3 (catalyst D).
2.4. Hydrogenation of methyl benzoate and 2-(4-carbo-
methoxyphenyl)-1,3-dioxane
Hydrogenation experiments were carried out under a
hydrogen pressure of 20 atm in a 75 ml stainless-steel
autoclave equipped with a removable Teflon liner, a
magnetic bar, a stainless-steel sampling valve and a
manometer (100 atm scale), submerged in an oil bath at
constant temperature (ꢁ1.0 °C).
P
P
da ¼ dini= ni, where ni is the number of particles of
diameter di. Histograms of the metal particle size dis-
tribution, the average particle diameter (da) and the
standard deviation (rÞ were determined by HRTEM.
The counting was carried out on electron micrographs
taken at 130.000 magnification and in this condition the
standard deviation resulted ꢁ0.5 nm. Elemental analy-
ses were carried out by the Laboratorio di Microanalisi,
In a typical experiment, the reactant (3.5 mmol),
catalyst (0.035 mg atom Ru) and reaction medium (10
ml) were charged into the autoclave under argon at-
mosphere. The autoclave was closed, argon was evacu-
ated and hydrogen was introduced up to 20 atm. The
progress of the reaction was monitored by analyzing
liquid samples taken from the sampling tap by GC and
NMR.
ꢀ ꢀ
Facolta di Farmacia, Universita di Pisa, Italy.
2.5. Preparation of 4-carbomethoxyformylcyclohexane
from methyl 4-formylbenzoate, 1
2.2. Preparation of the ruthenium on c-Al2O3 catalysts
In a typical experiment Ru(g6-COT)(g4-COD) (0.5 g,
1.58 mmol) was dissolved in THF (20 ml) and the re-
sulting yellow solution was added to a suspension of the
commercial c-Al2O3 (4.41 g) in THF (10 ml). Argon was
2.5.1. Synthesis of 2-(4-carbomethoxyphenyl)-1,3-diox-
ane, 2
Methyl 4-formylbenzoate (4 g, 24.4 mmol), 1,3-
propandiol (17.6 ml, 244 mmol) and anhydrous CuSO4

G. Marconi et al. / Journal of Organometallic Chemistry 689 (2004) 639–646
641
7
(1.6 g, 10 mmol) were introduced in a Carius tube. The
tube was closed and the reaction mixture was stirred at
95 °C for 3 h. After cooling the mixture was extracted
with ether (4 ꢀ 25 ml). The combined ether extracts were
dried over anhydrous sodium sulphate and concentrated
under reduced pressure. The resulting solution (10 ml)
was cooled to –30 °C for crystallisation of 2-(4-carbo-
methoxyphenyl)-1,3-dioxane, 2 (5.2 g, 23.4 mmol, yield
96%).
6
O
O
5
4
3
2
1
9
8 COOMe
5
3
4
O
O
Anal.: found: C, 63.32; H, 8.64%. C12H20O4 requires:
C, 63.13; H, 8.83%. 1H NMR: d, cis isomer, 4.3 (d, H5),
4.08 (m, H6;ax), 3.7 (m, H6;eq), 3.64 (s, H9), 2.51 (m, H1),
2.35 (m, H7), 1.74 (m, H3), 1.62 (m, H2), 1.53 (m, H4);
trans isomer 4.21 (d, H5), 4.02 (m, H6; eq), 3.66 (m,
H6; ax), 3.64 (s, H9), 2.4 (m, H7), 2.18 (m, H1), 1.81 (m,
H3), 1.69 (m, H2), 1.47 (m, H4). 13C NMR: d, cis isomer,
175 (C8), 104.1 (C5), 66.9 (C6), 51.3 (C9), 40.8 (C4), 39.9
(C1), 26.09 (C3), 25.95 (C7), 24.05 (C2); trans isomer, 176
(C8), 104.8 (C5), 66.9 (C6), 51.3 (C9), 43.1 (C1), 41.8
(C4), 28.29 (C3 + C7), 26.23 (C2). GC–MS, m/z (rel. int.
%): 228 (Mþ, 1); 227 (2.5); 226 (1); 197 (5); 169 (1); 152
(2); 93 (6); 87 (100); 81 (10); 67 (3); 59 (5).
3
2
1
6
COOMe
2
M.p. ¼ 89–91 °C. Anal.: found: C, 65.04; H, 6.21%.
C12H14O4 requires: C, 64.85; H, 6.35%. 1H NMR: d 8.05
(d, 2H, H1); 7.55 (d, 2H, H2); 5.52 (s, 1H, H3); 4.3 (m,
2H, H4); 4.05 (m, 2H, H4); 3.9 (s, 3H, H6); 2.35–2.15 (m,
1H, H5); 1.6–1.4 (m, 1H, H5). GC–MS, m/z (rel. int. %):
222 (Mþ, 71); 221 (68); 163 (29); 149 (10); 133 (42); 105
(65); 87 (28); 77 (76); 51 (52); 42 (100).
2.5.3. Transacetalization reaction of 2-(4-carbomethoxy-
cyclohexyl)-1,3-dioxane, 3, to 4-carbomethoxycyclohexyl
dimethyl acetal, 4
A
mixture of 2-(4-carbomethoxycyclohexyl)-1,3-
dioxane (4.0 g, 17.5 mmol), methanol (80 ml) and con-
centrated HCl (1 ml) was refluxed in an one necked
round-bottomed flask equipped with a reflux condenser
and a magnetic stirrer for 24 h. The reaction mixture
was extracted with ether (4 ꢀ 30 ml). After ether was
evaporated, 4-carbomethoxycyclohexyl dimethyl acetal,
4, was obtained and used in the next hydrolysis without
purification.
2.5.2. Catalytic hydrogenation of 2-(4-carbomethoxyphe-
nyl)-1,3-dioxane, 2, to 2-(4-carbomethoxy cyclohexyl)-
1,3-dioxane, 3
The hydrogenation of the aromatic ring in
2-(4-carbomethoxyphenyl)-1,3-dioxane to 2-(4-carbo-
methoxycyclohexyl)-1,3-dioxane was performed in a
stainless-still autoclave following the experimental pro-
cedure described in Section 2.4. 2-(4-Carbomethoxy-
phenyl)-1,3-dioxane (5 g, 22.5 mmol) was dissolved in
THF (20 ml) and Ru(TOA)/c-Al2O3 (catalyst D, 0.664
g, 0.23 mg atom Ru) was added to the solution. The
mixture was charged into the autoclave and heated to
80 °C in the presence of 20 atm of hydrogen. At complete
conversion of 2-(4-carbomethoxyphenyl)-1,3-dioxane
(ca. 24 h) the autoclave was cooled to room tempera-
ture, hydrogen was carefully evacuated and the catalyst
was removed by filtration. The solvent was evaporated
under reduced pressure and the residue was dissolved in
THF (10 ml). The solution was filtered through a celite
column followed by solvent removal in vacuo. 2-(4-
Carbomethoxycyclohexyl)-1,3-dioxane, 3, (4.63 g, 20.3
mmol, trans/cis ratio of 0.5) was obtained with a yield
of 90%.
2.5.4. Hydrolysis of 4-carbomethoxycyclohexyl dimethyl
acetal, 4, to 4-carbomethoxy formylcyclohexane, 5
4-Carbomethoxycyclohexyl dimethyl acetal, obtained
from the above experiment, was placed in an one necked
round bottomed flask equipped with a magnetic stirrer.
Water (150 ml) and concentrated HCl (1 ml) were added
and the mixture was stirred at room temperature for 4 h
followed by extraction with ether (4 ꢀ 50 ml). The ex-
tracted phase was dried over sodium sulphate and ether
was removed under reduced pressure. The residue was
then distilled to give pure 4-carbomethoxyformylcyclo-
hexane, 5, (2.67 g, 15.7 mmol, yield ¼ 90%, trans/
cis ¼ 2.3).

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G. Marconi et al. / Journal of Organometallic Chemistry 689 (2004) 639–646
5 CHO
3.1.2. Supported Ru/c-Al2O3 catalysts prepared in the
presence of TOA as a stabilizer
4
Deposition of the ruthenium nanoparticles stabilized
by the trioctylamine on alumina involved two steps.
Ru(g6-COT)(g4-COD) complex was first dissolved in
THF containing TOA (TOA: Ru molar ratio ¼ 3) under
hydrogen atmosphere. The solution gradually became
brown and no precipitation of metallic ruthenium was
observed as a result of the interaction of TOA on the
ruthenium nanoparticles. The solution was slowly dis-
coloured upon addition of c-Al2O3 and, at the com-
pletion of the reaction, a light brown solid, supported
Ru(TOA)/c-Al2O3 catalyst, was obtained. This overall
reaction is illustrated in Scheme 2.
3
2
1
7
6 COOMe
5
Anal.: found: C, 63.66; H, 8.14%. C9H14O3 requires: C,
63.5; H, 8.29%. 1H NMR: d, cis isomer, 4.3 (d, H5), 4.08
(m, H6; ax), 3.7 (m, H6; eq), 3.64 (s, H9), 2.51 (m, H1), 2.35
(m, H7), 1.74 (m, H3), 1.62 (m, H2), 1.53 (m, H4); trans
isomer 4.21 (d, H5), 4.02 (m, H6; eq), 3.66 (m, H6; ax), 3.64
(s, H9), 2.4 (m, H7), 2.18 (m, H1), 1.81 (m, H3), 1.69 (m,
H2), 1.47 (m, H4). 13C NMR: d, cis isomer, 204 (C5), 176
(C6), 51.7 (C7), 47.3 (C4), 40.9 (C1), 27.2 (C3), 24.85 (C2);
trans isomer, 203 (C5), 176 (C6), 51.5 (C7), 49.2 (C4), 42
(C1), 27.9 (C3), 25.7 (C2). GC–MS, m/z (rel. int. %): 170
(Mþ, 2); 152 (1); 138 (10); 110 (27); 109 (15); 93 (14); 92
(15); 81 (100); 79 (15); 77 (10); 67 (12); 59 (8); 55 (11).
3.2. Hydrogenation of methyl benzoate
The hydrogenation of unsaturated aromatic hydro-
carbons is a particularly important reaction in fine
chemical synthesis [1,2] and the hydrogenation of methyl
benzoate, as an example of deactivated aromatic com-
pound, appears to be a useful model reaction of this type.
Table 1 summarises the results obtained on the hydro-
genation of methyl benzoate to methyl cyclohexanoate
over different catalysts. The experiments were performed
at 80 °C and 20 atm hydrogen in THF or cyclohexane.
As can be seen from Table 1, the catalyst activity of
supported Ru catalyst, expressed as specific activity, was
increased significantly as the support surface area in-
creased. For both low and high surface area, the specific
activity increased by a factor of almost 1.5 when THF
was replaced by cyclohexane as reaction medium (runs
1–4). Further increase in catalyst activity was obtained
when TOA was used as metal particle stabilizer (runs 5–
8) and no evidence of catalyst deactivation was found
(runs 9–12).
3. Results and discussion
3.1. Synthesis of the supported ruthenium on c-alumina
catalysts
3.1.1. Supported Ru/c-Al2O3 prepared without trioctyl-
amine (TOA) addition
Nanoparticles of ruthenium were deposited on c-
Al2O3 supports (both commercial low surface area and
synthetic high surface area samples) by decomposition
of Ru(g6-COT)(g4-COD) under atmospheric hydrogen
at room temperature. This complex can be easily pre-
pared by reduction of hydrated RuCl3 with zinc dust in
the presence of COD [21]. The formation of supported
Ru/c-Al2O3 is presented in Scheme 1.
The catalyst activities for all catalysts prepared in this
study were significantly higher than that obtained on
commercial catalyst (run 13). The most active catalyst
prepared in this study (run 8) exhibits almost 10 times
higher in activity compared with a commercial available
catalyst.
3.3. High Resolution Transmission Electron Microscopy
(HRTEM) study of the Ru on c-Al2O3 catalysts, A-D
The metal dispersion appears to be the main factor
contributing to the catalyst activity as found by
Scheme 1.
Scheme 2.

G. Marconi et al. / Journal of Organometallic Chemistry 689 (2004) 639–646
643
Table 1
Hydrogenation of methyl benzoate to methyl cyclohexanoate with ruthenium on c-Al2O3 catalysts at 20 atm hydrogen pressure and 80 °Ca
Run
1
Catalystb
Solvent
THF
Time (h)
Conversionc (%)
Specific activity (SA)d
A
5
24
5
5
70
2.9
4.2
4.5
6.2
3.5
5.5
6.2
2
3
4
5
6
7
8
B
A
B
C
D
C
D
‘‘
15
24
5
100
20
Cyclohexane
22
5
100
50
‘‘
16
5
100
10
THF
24
5
85
40
‘‘
18
5
100
50
Cyclohexane
‘‘
16
5
100
90
8
100
100
100
100
100
35
12.5
4.5
9
10
11
12
13
A (recovered from run 3)
B (recovered from run 4)
C (recovered from run 7)
D (recovered from run 8)
Ru on c-Al2O3 (commercial)
22
16
16
8
‘‘
‘‘
‘‘
‘‘
6.2
6.2
12.5
1.4
24
a Methylbenzoate, 0.44 ml (3.5 mmol); catalyst (3.5 wt% Ru), 0.1 g (0.035 mg atom Ru); solvent, 10 ml.
b A ¼ Ru on commercial c-Al2O3; B ¼ Ru on high surface area c-Al2O3; C ¼ Ru(TOA) on commercial c-Al2O3; D ¼ Ru(TOA) on high surface area
c-Al2O3.
c Determined by GC analysis.
d SA ¼ moles of converted substrate/g atom ruthenium ꢀ h.
HRTEM (Figs. 1–4). The average metal particle size of
catalysts prepared in this study was in the range of 2.3–
2.9 nm and the catalyst activity was found to be as a
function of metal dispersion. Of the catalysts test, cat-
alyst D, with a smallest average metal particle size, ex-
hibits the highest activity. The metal dispersion was
remained unchanged during the course of the reaction.
A similar metal dispersion was found for catalyst D
recovered from run 8 and, as can be seen from Table 1,
this catalyst afforded similar activity when it was recy-
cled for the next run.
3.4. Preparation of 4-carbomethoxyformylcyclohexane
via catalytic hydrogenation of 2-(4-carbomethoxyphe-
nyl)-1,3-dioxane to 2-(4-carbomethoxycyclohexyl)-1,3-
dioxane
4-Carbomethoxyformylcyclohexane is an important
material in the synthesis of trans-4-aminomethylcyc-
lohexancarboxylic acid (known as tranexamic acid), a
compound of considerable pharmaceutical interest
[23,24]. In this study a new catalytic synthetic pathway
for the preparation of 4-carbomethoxyformylcyclohex-
ane from methyl 4-formylbenzoate has been studied and
Fig. 1. Electron micrograph of the ruthenium on commercial c-Al2O3
sample, catalyst A, and metal particle size distribution.
illustrated in Scheme 3.
Methyl 4-formylbenzoate cannot be directly hydro-
genated to 4-carbomethoxyformylcyclohexane as the
aldehyde group is reduced more easier than the aromatic
ring. For this reason it is necessary to protect the alde-
hyde group in methyl 4-formylbenzoate by a reversible
formation of a new functional group which is stable

644
G. Marconi et al. / Journal of Organometallic Chemistry 689 (2004) 639–646
Fig. 2. Electron micrograph of the ruthenium on high surface c-Al2O3
sample, catalyst B, and metal particle size distribution.
Fig. 4. Electron micrograph of the ruthenium on high surface c-Al2O3
sample, containing trioctylamine, catalyst D, and metal particle size
distribution.
under the hydrogenation conditions and can subse-
quently be removed. Cyclic acetals possess these features
and the transformation of methyl 4-formylbenzoate to
2-(4-carbomethoxyphenyl)-1,3-dioxane was considered.
This compound was synthesised by its reaction with
CHO
CHO
CH2NH2
COOH
COOMe
COOMe
1
5
6
i
iv
O
O
O
O
MeO
OMe
ii
iii
COOMe
COOMe
COOMe
2
3
4
Scheme 3. (i) 1,3-Propandiol anhydrous CuSO4, heat, yield 95%;
(ii) H2 (20 atm), Ru(TOA)/c-Al2O3 (catalyst D), yield 90%;
(iii) methanol, HCl, heat, and (iv) acidic water, 25 °C, yield 90%.
Fig. 3. Electron micrograph of the ruthenium on commercial c-Al2O3
sample, containing trioctylamine, catalyst C, and metal particle size
distribution.

G. Marconi et al. / Journal of Organometallic Chemistry 689 (2004) 639–646
645
1,3-propandiol at 95 °C (Scheme 3, step i), in which
anhydrous CuSO4 was used both as a Lewis acidic
catalyst and as a dehydrating agent to shift the equi-
librium towards the formation of the product. The
conversion of methyl 4-formylbenzoate was completed
after 3 h and 2-(4-carbomethoxyphenyl)-1,3-dioxane can
be recovered with a very high yield (95%), similar to that
reported for the formation of 2-phenyl-1,3-dioxane by
reaction of benzaldehyde and 1,3-propandiol [26].
The next step consists in the catalytic hydrogenation
of 2-(4-carbomethoxyphenyl)-1,3-dioxane to 2-(4-car-
bomethoxycyclohexyl)-1,3-dioxane (Scheme 3, step ii).
This reaction is the key step in the synthesis of 4-car-
bomethoxyformylcyclohexane because of the difficulty
to carry out the reduction of the aromatic ring without
side reactions on other functional groups present in the
molecule. The reaction was tested with ruthenium on c-
alumina catalysts prepared in this study at 80 °C and 20
atm of hydrogen. THF, being a good solvent for 2-(4-
carbomethoxyphenyl)-1,3-dioxane, was used as a reac-
tion medium. The results obtained are reported in Table
2. Catalysts A and B exhibit a similar activity giving 70
and 75% yield of 2-(4-carbomethoxycyclohexyl)-1,3-di-
oxane after 24 h, respectively (runs 14 and 15). Catalysts
C and D in which TOA was used in the preparation
procedure as a metal particle stabilizer are more active
giving 95% and 100% yield of 2-(4-carbomethoxy-
cyclohexyl)-1,3-dioxane after 20 h, respectively (runs 16
and 17). The reaction was also performed without
solvent over catalyst D at 95 °C [melting point of 2-(4-
carbomethoxyphenyl)-1,3-dioxane] (run 18). A complete
conversion of 2-(4-carbomethoxyphenyl)-1,3-dioxane
after 15 h was obtained with only a slight loss of selec-
tivity to afford 2-(4-carbomethoxycyclohexyl)-1,3-diox-
ane, in 95% yield.
perimental section) was carried out in THF with catalyst
D, following the conditions of run 17 (Table 2). 2-(4-
Carbomethoxycyclohexyl)-1,3-dioxane was obtained as
a mixture of cis trans isomers ratio of 0.5.
The final step consists of the removal of the protecting
propandioxy group in 2-(4-carbomethoxycyclohexyl)-
1,3-dioxane and the regeneration of the aldehyde group.
The most common method employed for acetal breakage
is acid-catalysed hydrolysis. However for cyclic acetals in
2-(4-carbomethoxycyclohexyl)-1,3-dioxane, the reaction
rate is low. Attempts to perform the hydrolysis of 2-(4-
carbomethoxycyclohexyl)-1,3-dioxane with HCl at
different concentration, in water-acetone and water-
dioxane mixtures, as reported for dioxolanic cycles
[27,28] were unsuccessful due to a very low reaction rate
at room temperature and side reactions under reflux
conditions. The formation of an acyclic acetal, by a
transacetalisation reaction, was considered as an alter-
native route, as acyclic acetals are less stable than the
cyclic ones and their hydrolysis is easier to perform.
Following this procedure, 2-(4-carbomethoxycyclo-
hexyl)-1,3-dioxane was refluxed with methanol in the
presence of concentrated HCl as a catalyst. This step
formed 4-carbomethoxycyclohexyl dimethyl acetal,
which was in turn hydrolysed in situ to give 2-(4-car-
bomethoxycyclohexyl)-1,3-dioxane with 90% yield
(Scheme 3, steps iii and iv, respectively). Due to a partial
conversion of cis- to trans-isomer occurring during
these reactions, the product is enriched in trans-isomer
(70%). This observation is of particular relevance as
only the trans-isomer of 4-aminomethylcyclohexan-
carboxylic acid (tranexamic acid) is biologically active
[23,24].
For this reason, in order to avoid difficult and
expensive steps for the purification of 2-(4-carbo-
methoxycyclohexyl)-1,3-dioxane, the synthesis of
2-(4-carbomethoxycyclohexyl)-1,3-dioxane from 2-(4-
carbomethoxyphenyl)-1,3-dioxane in large scale (see ex-
4. Conclusions
The Ru/c-Al2O3 systems obtained using the com-
plex Ru(g6-COT)(g4-COD) as source of nanoscale
ruthenium particles appear to be valuable catalysts for
Table 2
Hydrogenation of 2-(4-carbomethoxyphenyl)-1,3-dioxane, 2, to 2-(4-carbomethoxycyclohexyl)-1,3-dioxane, 3, with ruthenium on c-Al2O3 catalysts
at 20 atm hydrogen pressure and 80 °C in THFa
Run
Catalystb
Time (h)
Conversionc (%)
Compound 3c;d(%)
Specific activitye (SA)
14
15
16
17
18f
A
B
C
D
D
24
24
20
20
15
70
75
70
75
2.9
3.1
4.7
5.0
6.3
95
95
100
100
100
95
a 2-(4-Carbomethoxyphenyl)-1,3-dioxane, 2, 0.77 g (3.5 mmol); catalyst (3.5 wt% Ru), 0.1 g (0.035 mg atom Ru); THF, 10 ml.
b A ¼ Ru on commercial c-Al2O3; B ¼ Ru on high surface area c-Al2O3; C ¼ Ru(TOA) on commercial c-Al2O3; D ¼ Ru(TOA) on high surface area
c-Al2O3.
c Determined by GC and 1H NMR analyses.
d cis/trans ¼ 2.
e SA ¼ moles of compound 3/g atom ruthenium ꢀ h.
f Performed without solvent.

646
G. Marconi et al. / Journal of Organometallic Chemistry 689 (2004) 639–646
€
[6] M.T. Reetz, W. Helbig, S.A. Quaiser, in: A. Furstner (Ed.), Active
Metals: Preparation, Characterization, Applications, VCH, New
York, 1996.
the hydrogenation of arenes containing electron-with-
drawing groups such as methyl benzoate and 2-(4-car-
bomethoxyphenyl)-1,3-dioxane under mild conditions.
The catalysts C and D, prepared in the presence of TOA
as metal particle stabilizer, show the better catalytic ac-
tivity, reasonably as result of a high metal dispersion, the
ruthenium particles ranging 2.3–2.4 nm vs 2.8–2.9 nm in
samples A and B. The effect of TOA on metal dispersion
has been recently observed and widely discussed for
rhodium-TOA on c-Al2O3 systems [29,30]. It is reason-
able to suppose a similar effect for Ru-TOA/c-Al2O3
systems, in which Ru particles are surrounded by trioc-
tylamine that stabilizes them in a form of high dispersion
and prevents their agglomeration and poisoning. No
evidence of catalyst deactivation was found and catalysts
could be reused several times without loss of activity.
€
[7] H. Bonnemann, G. Braun, W. Brijoux, R. Brinkmann, A.S.
Tilling, K. Seevogel, K. Siepen, J. Organomet. Chem. 520 (1996)
143.
[8] Y. Wang, H. Liu, N. Toshima, J. Phys. Chem. 100 (1996) 19533.
[9] G. Vitulli, A. Verrazzani, A.M. Caporusso, E. Pitzalis, P. Pertici,
P. Salvadori, in: S. Daolio, E. Tondello, P.F. Vigato (Eds.),
Syntheses and Metodologies in Inorganic Chemistry, New Com-
pounds and Materials, vol. 7, 1997, p. 52.
[10] G. Vitulli, E. Pitzalis, A. Verrazzani, P. Pertici, P. Salvadori, G.
Martra, Mater. Sci. Forum. 235-238 (1997) 929.
[11] K.S. Weddle, J.D. Aiken III, R.G. Finke, J. Am. Chem. Soc. 120
(1998) 5653.
[12] N. Toshima, T. Yonazawa, New J. Chem. 22 (1998) 1179.
[13] J. Schulz, A. Roucoux, H. Patin, J. Chem. Soc. Chem. Commun.
(1999) 535.
[14] G.B. Sergeev, Russ. Chem. Rev. 70 (2001) 809.
[15] N. Toshima, Y. Shiraishi, T. Teranishi, M. Miyake, T. Tominaga,
€
H. Watanabe, W. Brijoux, H. Bonnemann, G. Schmid, Appl.
Organomet. Chem. 15 (2001) 178.
€
[16] H. Bonnemann, R. Richards, Eur. J. Inorg. Chem. (2001) 2455.
Acknowledgements
[17] A. Spitaleri, P. Pertici, N. Scalera, G. Vitulli, M. Hoang, T.W.
Turney, M. Gleria, Inorg. Chim. Acta 352 (2003) 61.
[18] H. Hirai, H. Chawanya, N. Toshima, React. Polym. 3 (1985) 127.
[19] G. Schmid, Chem. Rev. 92 (1992) 1709.
The authors thank CNR (Italy) and CSIRO (Aus-
tralia) for the financial support in a CNR–CSIRO
Collaborative Research Scheme; a partial support by
Ministero dellÕIstruzione, Universita e Ricerca (MIUR,
Italy) is also acknowledged.
[20] V.M. Frolov, Platinum Met. Rev. 40 (1996) 8.
[21] P. Pertici, G. Vitulli, Inorg. Syn. 22 (1983) 176.
[22] C. Pan, K. Peltzer, K. Philippot, B. Chaudret, F. Dassenoy, P.
Lecante, M-J. Casanove, J. Am. Chem. Soc. 123 (2001) 7584.
[23] C. Runti, in: Fondamenti di Chimica Farmaceutica, vol. III, Lint,
Trieste, Italy, 1989, 465.
ꢀ
[24] K. Maeda, M. Naganuma, J. Photochem. Photobiol. B 47 (1998)
136.
References
[25] M. Giannos, M. Hoang, T.W. Turney, Chem. Lett. 27 (1998) 793.
[26] R.P. Hanzlik, M. Leinwetter, J. Org. Chem. 43 (1978) 438.
[27] M.L. Bender, M.S. Silver, J. Am. Chem. Soc. 85 (1963) 3006.
[28] E.H. Cordes, H.G. Bull, Chem. Rev. 74 (1974) 580.
[29] G. Vitulli, C. Evangelisti, P. Pertici, E. Pitzalis, A.M. Caporusso,
P. Salvadori, S. Coluccia, G. Martra, A. Balerna, S. Mobilio,
Second European Catalysis Simposium, Pisa, Italy, 23–26 Sep-
tember 2001, abstract P75.
[1] J.D. Aiken III, R.G. Finke, J. Mol. Cat. A 145 (1999) 1, and
references therein.
[2] J.A. Widegren, R.G. Finke, J. Mol. Cat. A 191 (2003) 187, and
references therein.
[3] S. Abbet, A. Sanchez, U. Heiz, W.-D. Schneider, A.M. Ferrari, G.
€
Pacchioni, N. Rosch, J. Am. Chem. Soc. 122 (2000) 3453, and
references therein.
[30] G. Vitulli, C. Evangelisti, P. Pertici, A.M. Caporusso, N.
Panziera, P. Salvadori, M.G. Faga, C. Manfredotti, G. Martra,
S. Coluccia, A. Balerna, S. Colonna, S. Mobilio, J. Organomet.
Chem. 681 (2003) 37.
[4] R. Rao, G.U. Kulkarni, P.J. Thomas, P.P. Edwards, Chem. Eur.
J. 8 (2002) 29, and references therein.
[5] K.J. Klabunde, Free Atoms, Clusters and Nanoscale Particles,
Academic Press, New York, 1994.