Green and selective toluene oxidation–Knoevenagel-condensation domino reaction over Ce- and Bi-based CeBi mixed oxide mixtures

Article abstract of DOI:10.1016/j.jcat.2019.11.011

Both Bi- and Ce-based CeBi mixed oxides were prepared by a modified sol-gel process from their precursor salts. The mixed as well as the parent oxides were characterized by X-ray diffractometry, Raman, XPS, UV–DRS and X-ray photoelectron spectroscopies, ICP–OES method, scanning and transmission electron microscopies as well as BET surface area, CO₂- and NH₃-temperature-programmed desorption measurements. After characterizing the morphology, the acid-base properties, the oxidation states of the cationic components and the porosity of these structures, their catalytic activities were probed in the Koevenagel condensation of benzaldehyde and diethyl malonate and the toluene oxidation to benzaldehyde reactions. Based on the catalytic activities of the oxides in the individual reactions, a catalyst mixture from the Bi- and Ce-based mixed oxides was used successfully in the toluene to benzaldehyde oxidation and benzaldehyde to benzylidene malonate Knoevenagel condensation domino reaction under environmentally benign conditions.

Full text of DOI:10.1016/j.jcat.2019.11.011

Journal of Catalysis 381 (2020) 308–315
Contents lists available at ScienceDirect
Journal of Catalysis
journal homepage: www.elsevier.com/locate/jcat
Green and selective toluene oxidation–Knoevenagel-condensation
domino reaction over Ce- and Bi-based CeBi mixed oxide mixtures
c
Gábor Varga a,b, , Ákos Kukovecz , Zoltán Kónya c,d, Pál Sipos b,e, István Pálinkó a,b,
⇑
*
a Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged H-6720, Hungary
b Materials and Solution Structure Research Group and Interdisciplinary Excellence Centre, Institute of Chemistry, University of Szeged, Aradi Vértanúk tere 1, Szeged H-6720, Hungary
c Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Béla tér 1, Szeged H-6720, Hungary
d MTA-SZTE Reaction Kinetics and Surface Chemistry Research Group, Rerrich Béla tér 1, Szeged H-6720, Hungary
e Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, Szeged, H-6720, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Both Bi- and Ce-based CeBi mixed oxides were prepared by a modified sol-gel process from their precur-
sor salts. The mixed as well as the parent oxides were characterized by X-ray diffractometry, Raman, XPS,
UV–DRS and X-ray photoelectron spectroscopies, ICP–OES method, scanning and transmission electron
microscopies as well as BET surface area, CO2- and NH3-temperature-programmed desorption measure-
ments. After characterizing the morphology, the acid-base properties, the oxidation states of the cationic
components and the porosity of these structures, their catalytic activities were probed in the Koevenagel
condensation of benzaldehyde and diethyl malonate and the toluene oxidation to benzaldehyde reac-
tions. Based on the catalytic activities of the oxides in the individual reactions, a catalyst mixture from
the Bi- and Ce-based mixed oxides was used successfully in the toluene to benzaldehyde oxidation
and benzaldehyde to benzylidene malonate Knoevenagel condensation domino reaction under environ-
mentally benign conditions.
Received 14 August 2019
Revised 3 November 2019
Accepted 8 November 2019
Keywords:
CeBi-oxide solid solutions
Comprehensive structural characterization
Knoevenagel condensation on the solid
bases
Toluene oxidation on the Ce-centres
Oxidation and Knoevenagel condensation
domino reaction over the mixed CeBi oxides
Environmentally benign conditions
Ó 2019 Elsevier Inc. All rights reserved.
1. Introduction
the industrial level was not possible because of various reasons like
the high price of the catalysts. As for now, despite their demon-
Knoevenagel condensation [1] is a still frequently applied reac-
tion in, for instance, the synthesis of some new drugs. They are
strated outstanding efficiency, the high price of ionic liquids
[10–12] are also against their wide spread use.
atorvastatin [2]
a
well-known cardiovascular pharmaceutical,
The second group is developing water-based reactions. Due to
the inexpensive and environmentally friendly nature, water-
based reactions [13–15] are desirable even if occasionally, the rate
of the reaction is lower than in organic medium. However, if new
types of catalysts are devised, which work in aqueous environ-
ment, the reaction rate may become comparable to the one run-
ning in organic solvent.
pioglitazone [3] used to treat diabetes mellitus type 2 or MDL
103371 [4], which is a glycine receptor antagonist for the treat-
ment of stroke to mention just a few. Considering the strict envi-
ronmental laws and that the pharmaceuticals mentioned are
produced on a large scale, greening each reaction step, and thus
the Knoevenagel reaction too, was and still is a must.
The environmentally benign improvements of the condensation
reaction can be divided into two groups.
In connection with the second group, porous as well as layered
structures were probed as catalysts in Knoevenagel reaction. Zeo-
lites [16,17], montmorillonite [18], layered double hydroxides
[19,20] and their modified versions [21,22] displayed advanta-
geous features from increasing the selectivity to decreasing the
reaction time. However, either the reusability or the general appli-
cability of the catalysts often caused serious problems. Basic mixed
oxides such as MgAl [23], NiMo [24] and others [25] have well-
known structures, they are easy to synthesize, have outstanding
activities and selectivities; nevertheless, stability issues may arise
due to excessive leaching. Among them, the CeZr mixed oxide
The application of environmentally benign solvents like ionic
liquids and using alternative methods like solvent-free synthesis,
high pressure [5,6], special gaseous catalysts [7] or microwave irra-
diation [8,9] belong to the first group. Although these methods
worked in the laboratory scale, scaling them up to be useful at
⇑
Corresponding authors at: Department of Organic Chemistry, University of
Szeged, Dóm tér 8, Szeged H-6720, Hungary.
E-mail addresses: gabor.varga5@chem.u-szeged.hu (G. Varga), palinko@chem.
u-szeged.hu (I. Pálinkó).
https://doi.org/10.1016/j.jcat.2019.11.011
0021-9517/Ó 2019 Elsevier Inc. All rights reserved.

G. Varga et al. / Journal of Catalysis 381 (2020) 308–315
309
[26] was particularly interesting, since short reaction time was
needed, and nearly full conversion was reached.
powder-like samples were evenly laid out on one side of a
double-sided adhesive tape, the other side being attached to the
sample holder of the XPS instrument. The samples were evacuated
at room temperature, and then inserted into the analysis chamber
of the XPS instrument.
Based on these preliminaries, we planned to synthesize a CeBi
mixed oxide to use as catalyst in Knoevenagel reaction and to
develop a green synthesis route. The motivation for application
of bismuth as dopant was that new studies proved the catalytic
potential of Bi-containing systems of basic character [27,28], which
should be advantageous in this reaction too. Moreover, in order to
establish an economically friendly process, toluene [29] was used
as the starting reactant. This way, an eco- and environmentally
friendly domino reaction system was created.
BET surface area measurements were performed on
a
NOVA3000 (Quantachrome) instrument. The samples were
degassed with N2 at 100 °C for 5 h under vacuum to clean the sur-
face of adsorbed materials. The measurements were performed at
the temperature of liquid N2.
The basic and acid sites of the samples were characterized by
temperature-programmed desorption (TPD) measurements using
99.9% CO2/He and 0.3% NH3/He, respectively. TPD analysis was per-
formed on a Hewlett-Packard 5890 GC system equipped with
thermo-conducting detector. Before the measurements, the mixed
oxides were purified by heat treatment at 500 K under He flow.
The actual ratios of metal ions in the mixed oxides were deter-
mined by Perkin Elmer Optima 7000DV Inductively Coupled
Plasma Optical Emission (ICP–OES) spectrometer. Yttrium internal
standard was used for each measurement. Before measurements,
few milligrams of the samples measured by analytical accuracy
were dissolved in 5 mL cc. HNO3. After dissolution, the samples
were diluted with distilled water to 100 mL and filtered.
Quantitative data for the oxygen content could not be mea-
sured, but on the basis of ref. [30], an approximate oxygen content
for the phase-pure materials is given.
2. Experimental
2.1. Materials and syntheses of the oxides
All the chemicals (Bi(NO3) Â 5 H2O, Ce(SO4)2 Â 4 H2O,
CeO2, Bi2O3, NaOH ethylene glycol) were of reagent grade, and
were purchased from Merck or Sigma-Aldrich, and were used with-
out further purification.
The catalysts were prepared by
a
colloidal phase
co-precipitation method. Aqueous -propanol suspensions (V =
25 mL) with varying amounts of Bi(NO3) Â 5 H2O (n = 6 Â 10À5 À 6
 10À4 mol) were made and treated by a 15-minute-long ultrasonic
irradiation followed by the addition of 10 mL ethylene glycol to
establish a set of sols. After that, the sols were stirred at 50 °C for
60 min. A second suspension of Ce(SO4)2 Â 4 H2O (n = 6 Â 10À4 mol)
was also prepared. This suspension was treated the same way as the
bismuth-containing systems. Under continuous stirring, the
cerium-containing suspension was added dropwise to the
bismuth-containing sols. The mixtures were stirred at room
temperature for 60 min. Then 0.15 M NaOH (V = 25 mL) was added
dropwise until gelation. The gels were stirred at 70 °C for 168 h. The
materials obtained were separated by evaporation followed by
filtration, washed with hot (~60 °C) distilled water and propanol
several times, and dried at 130 °C for 24 h.
2.3. General procedures for the catalytic reactions
Knoevenagel condensation: The compound with active methy-
lene group (1.5 mmol), benzaldehyde or its derivative (1.0 mmol)
and dodecane as internal standard were dissolved in 3 mL of sol-
vent to get a clear solution. The reaction was quenched after
5 min with 6 N ice-cold HCl. The product was extracted with ethyl
acetate (3 Â 10 mL). The combined organic extracts were dried
using anhydrous sodium sulphate, evaporated under reduced pres-
sure, and assayed on a GC. Conversions in all cases were monitored
with respect to the decay of the aldehyde on GC. Hewlett-Packard
5890 chromatograph equipped with a flame ionization detector
was employed for the analysis.
Toluene oxidation was carried out as follows: catalyst in 2.3 mL
solvent, toluene (8.3 M, 2.7 mL), TBHP (70%, 167 mM) (or other oxi-
dizing agent) were added into the flask. The reaction was carried
out at various reaction temperatures and monitored by gas
chromatography.
2.2. Characterization techniques
X-ray diffraction (XRD) patterns were recorded on
a
Rigaku XRD-MiniFlex II instrument applying Cu K radiation
a
(k = 0.15418 nm) with 40 kV accelerating voltage at 30 mA.
The morphologies of the freshly prepared samples were studied
by scanning electron microscopy (SEM). The SEM images were reg-
istered on an S-4700 scanning electron microscope (SEM, Hitachi,
Japan) with accelerating voltage of 10–18 kV. More detailed images
on the freshly prepared samples, were captured by transmission
electron microscopy (TEM). For these measurements, a FEI TecnaiTM
G2 20 X-Twin type instrument was used operating at an accelera-
tion voltage of 200 kV.
Domino reaction: the reactions were run at the optimized reac-
tion conditions for toluene oxidation. The transformations were
followed by gas chromatography.
3. Results and discussion
The Raman spectra were recorded with a Thermo Scientific TM
DXRTM Raman microscope at an excitation wavelength of 635 nm
applying 10 mW laser power and averaging 20 spectra with an
exposition time of 6 s. UV–vis spectra were registered on an Ocean
Optics USB4000 spectrometer with a DH-2000-BAL UV–vis–NIR
light source measuring diffuse reflectance, and using BaSO4 as ref-
erence. The spectra were analysed with the SpectraSuite package.
X-ray photoelectron spectra (XPS) were recorded using a SPECS
instrument equipped with a PHOIBOS 150 MCD 9 hemi-spherical
3.1. Comprehensive structural characterization of the oxides
In order to assign the actual molar ratio for the cationic compo-
nents of the mixed oxides, elemental analysis was performed by
the ICP–OES method (first and second columns of Table 1).
The XRD patterns of the as-prepared CeBi hybrid oxides are
shown in Fig. 1. As the patterns obtained attest, the structures of
the different CeBi hybrid materials were strongly influenced by
the concentrations of the cationic components. The diffraction
lines in diffractograms A–C could be indexed as a face-centred
cubic fluorite structure [31–34] of CeO2 (JCPDS No. 43-1002), and
no separate crystalline bismuth ion containing phases could be
identified, i.e., it is highly probable that Bi(III) ions were incorpo-
rated into the ceria lattice.
electron energy analyser using Al K
a radiation (hm = 1486.6 eV).
The X-ray gun was operated at 210 W (14 kV, 15 mA). The analyser
was operated in the FAT mode, with the pass energy set to 20 eV.
The step size was 25 meV, and the collection time in one channel
was 250 ms. Typically, 5–10 scans were added to acquire a single
spectrum. Energy referencing was not applied. In all cases the

310
G. Varga et al. / Journal of Catalysis 381 (2020) 308–315
Table 1
Characteristic information about the single oxides and the CeBi hybrid oxides prepared: +measured by ICP–OES, ++measured by CO2-TPD, +++calculated from XP spectra.
Ce:Bi nominal ratio
Ce:Bi actual ratio+
Amount of desorbed CO2 (mmol/g)++
BET surface area (m2/g)
Ce/Bi ratio on the surface+++
CeO2
9:1
8:2
7:3
6:4
nr
0
43
27
40
52
40
36
60
nr
4
12:1
10:1
9:1*
1.3:1
1:1.43*
nr
0.09
0.27
0.49
0.61
0.94
0
2.6
0.95
0.7
0.4
nr
1:1
Bi2O3
*
Chemical formula for the phase pure mixed oxides: 9:1 – Ce0.9Bi0.1O1.8, 1:1.43 – Ce0.4Bi0.6O1.7
.
Fig. 2. UV–DR spectra of: A: Bi2O3, B: physically mixed Bi2O3–CeO2 of 1:1 ratio, C:
CeO2, D: Ce0.9Bi0.1O1.8, E: Ce0.4Bi0.6O1.7
.
Fig. 1. XRD patterns for CeBi oxide materials with A: 9:1, B: 10:1, C: 12:1, D: 1.3:1,
E: 1:1.43 actual Ce:Bi molar ratios.
On increasing the Bi(III) concentration, new diffraction lines
were observed indicating the appearance of another phase (diffrac-
togram D). Here, the new pattern overlapped with that of fluorite.
Diffractogram E corresponding to the material with bismuth ions
in excess (CeBi1.43ox), displays the five characteristics peaks of
the monoclinic a-Bi2O3 (JCPDS No. 71-0465). b-Bi2O3 phase (JCPD
card No. 76-2478) is also detected (marked with *). However, sep-
arate ceria phases were not observed. This means that now cerium
ions were incorporated into the Bi2O3 lattice. The chemical formula
of the phase-pure substances are Ce0.9Bi0.1O1.8 and Ce0.4Bi0.6O1.7
.
(The oxygen content is an estimate based on ref. [30]). The calcu-
lated cell parameters of the phase-pure materials can be found in
STable 1 (figures and tables in the Supplementary Material file will
be referred as SFigure and STable, respectively).
In Fig. 2, the UV–DRS spectra of the CeO2, the Bi2O3 and the
CeO2–Bi2O3 samples are displayed. The reflection edge of CeO2–
Bi2O3 in the visible light range were red shifted compared to those
of the pure Bi2O3 and the pure CeO2. The light absorption would
exhibit increasing red shift with the increase in bismuth content.
In order to prove the structural incorporation, a spectrum of phys-
ically mixed oxide was also registered. The spectrum can be
derived as the sum of the spectra of the physically mixed pure oxi-
des. Both appearing transitions can be attributed to excitonic
absorption peaks (388 nm ? Bi2O3, 440 nm ? CeO2) belonging
to the pure starting materials [35,36].
Fig. 3. Raman spectra of for CeBi oxide materials with A: 9:1 (Ce0.9Bi0.1O1.8), B: 10:1,
C: 12:1, D: 1.3:1, E: 1:1.43 (Ce0.4Bi0.6O1.8) actual Ce:Bi molar ratios.
other hand, some intense peaks were also observed at 300 cmÀ1
and 600 cmÀ1 in the fluorite type oxide samples. The presence of
vibrations in the region associated with fluorite vibrations for the
material with Ce:Bi = 1.3:1 M ratio (spectrum B) suggests the pres-
ence of monoclinic structure with oxygen displacement [38]. In the
spectrum of the one with Ce:Bi = 9:1 M ratio (spectrum E), the only
In the Raman spectrum of the pure CeO2 sample (Fig. 3), in
accordance with literature results [37], a single F2g mode vibration
could only be observed at 450 cmÀ1. In the spectrum of Ce0.9Bi0.1ox
strong peak in the 100–400 cmÀ1 region was observed at 160 cmÀ1
This can be ascribed to Bi3+ cation motion in [BiO6] octahedron,
.
(spectrum A) this is the predominating band shifted to 440 cmÀ1
.
For the fluorite type mixed oxides, it is the decisive band. On the

G. Varga et al. / Journal of Catalysis 381 (2020) 308–315
311
which is described in the literature as the A1g mode [39]. In the
higher energy region, a peak at 405 cmÀ1 was observed, and
assigned to BiAOABi stretching vibrations in distorted [BiO6] units
[40]. In the spectra of the other mixed oxides with Ce excess
(spectra C and D), the characteristic features of the spectra of
Ce0.9Bi0.1O1.8 and Ce0.4B0.6O1.7 are seen, although the corresponding
bands were shifted (440 cmÀ1 ? 450 cmÀ1, 405 cmÀ1 ? 400 cmÀ1
175 cmÀ1 ? 190 or 180 cmÀ1) indicating once again that CeBi
oxides with mixed phases were produced.
on the CO2-TPD profiles (Fig. 6) reveal the presence of moderately
basic sites (Table 1) over the surfaces [45], while the pure CeO2 or
the Bi2O3 were found to be non-basic. Acid sites were not detected
by NH3-TPD measurements either over the mixed oxide or the
single oxide samples. It is seen that the amount of basic sites is
significantly lower for the fluorite-type materials than for the
monoclinic mixed oxides. These observations and the previously
discussed XPS results verify that the basicity of the materials can
mainly be attributed to the Bi(III) cations.
In order to learn about the oxidation states of the guest cations
in the phase-pure mixed oxides (Ce0.9Bi0.1O1.8, Ce0.4Bi0.6O1.7), XPS
measurements were performed (Fig. 4). Surprisingly, based on
the 3d photoelectron transition of Ce and 4f transition of Bi ions
[41–43], it was found that beside Bi(III), Ce(IV)/Ce(III) ions were
in the structures. Probably, part of the Ce(IV) ions were oxidized
by the ethylene glycol in the synthesis mixture to form Ce(III)
[44]. In addition, the incorporation of Ce(III) into the mixed oxide
structure inhibited its re-oxidation by air. The results from XPS
analysis (last column in Table 1) revealed the presence of much
higher percentage of bismuth on and near the surface in all sam-
ples than expected indicating that bismuth had a very strong pref-
erence to occupy surface sites.
3.2. Testing the catalytic behaviour in the Knoevenagel condensation
reaction
CeO2 did not show any activity in the condensation reaction of
benzaldehyde and diethyl malonate to produce benzylidene malo-
nate (Scheme 1) or other products under the same reaction condi-
tions as was used for the phase-pure mixed oxides.
The results (Table 2) show strong dependence on the amount of
basic sites (determined by CO2 adsorption and serving as the basis
of TOF calculations – see column 3 in Table 1) attributed to the Bi
(III) ions in the mixed oxides. It is known that Knoevenagel con-
densation is a base-catalysed reaction, the basic surface acts as
the proton scavenger to generate malonic ester anion, which is
the nucleophile attacking at the positively polarised carbonyl car-
bon (Scheme 2).
SEM images of the phase-pure mixed oxides are shown in Fig. 5.
Ce0.9O0.1ox has irregular cauliflower-like shape, while CeBi1.43ox
has semi regular, rounded cubic shape morphology.
The low BET surfaces indicate that non-porous structures were
produced (fourth column in Table 1). The maxima at about 450 K
Accordingly, the catalytic test reaction was further studied
using the Ce0.4Bi0.6O1.7 mixed oxide to identify optimum reaction
conditions. The conversion of the reaction could be increased up
to 80% by increasing the amount of catalyst from 0.005 to 0.02 g
(STable 2). The conversion could be further enhanced on applying
even larger catalyst loading; however, a drop in selectivity was
observed (last row in STable 2). A competing reaction, the Michael
addition appeared. Indeed, the benzylidene malonate could play
the role of Michael acceptor [46]. Accordingly, in further optimisa-
tion 0.02 g catalyst loading was used.
After determining the optimum catalyst loading, various sol-
vents such as ethanol, water, chloroform or acetonitrile were tried.
On using chloroform or acetonitrile, negligible conversions were
observed. The significantly greener polar protic ethanol was found
to be highly efficient. Here, we saw a possibility of further greening
the reaction: perhaps, aqueous ethanol or even water may also be
good or even better choices. As data in STable 3 shows, aqueous
ethanol or water proved to be good solvents; however, ethanol
remained the best.
The influence of temperature was investigated in the
25 °C–60 °C temperature range keeping the other parameters fixed
(STable 4). The increase of conversion along with the decrease in
selectivity was observed on increasing reaction temperature. Due
to the higher temperature, from 45 °C, decarboxylation also took
place providing with cinnamic acid [47]. Keeping the reaction tem-
perature as low as 25 °C, but increasing the reaction time to 10 h,
92% conversion could be reached maintaining 100% benzylidene
malonate selectivity. On further increasing the reaction time at this
temperature to 24 h, the conversion could be raised to 98%, still
maintaining 100% selectivity. However, 100% conversion and selec-
tivity within reasonable time could be reached at 35 °C reaction
temperature.
The recycling properties of the catalyst were studied using the
reaction conditions found to be optimal (1.0 eq of benzaldehyde,
1.5 eq of diethyl malonate, 0.02 g of Ce0.4Bi0.6O1.7, 35 °C reaction
temperature, 360 min reaction time, ethanol as solvent). After a
reaction, the catalyst was filtered, washed with ethanol and water
several times and dried at 60 °C overnight. The reaction was
repeated four times with the above treatments between the runs.
Conversions remained 100% or very close to it in the repeated runs,
while small gradual losses in selectivities were experienced, but
Fig. 4. XP spectra of: A: Ce0.4Bi0.6O1.7
energies of (a) Bi species and (b) Ce species.
, B: Ce0.9Bi0.1O1.8 mixed oxides; binding

312
G. Varga et al. / Journal of Catalysis 381 (2020) 308–315
Fig. 5. SEM images: A: Ce0.9Bi0.1O1.8, B: Ce0.4Bi0.6O1.7; TEM images: C: Ce0.9Bi0.1O1.8, D: Ce0.4Bi0.6O1.7
.
Table 2
Conversion/TOF and selectivity results of the Knoevenagel condensation between
benzaldehyde (1.0 eq) and diethyl malonate (1.5 eq); mcat = 0.015 g, T = 35 °C,
t = 180 min in ethanol.
Catalyst
CeO2
Conversion (%)/TOF (molecules/basic sites/h) Selectivity (%)
–
–
Ce0.9Bi0.1O1.8 17/7.2
Ce0.4Bi0.6O1.7 60/13.8
100
100
–
Bi2O3
–
Scheme 2. Deprotonation of diethyl malonate by base or basic sites.
the condensation selectivity was 92% even in the fourth repeated
run (Table 3).
The stability of the Ce0.4Bi0.6O1.7 catalyst on reuse was moni-
tored by ICP–OES, but measurable leaching of either Ce or Bi ions
could not be observed.
Fig. 6. CO2-T(emparature)P(rogrammed)D(esorption) spectra: A: CeO2, B: Ce0.9
-
Bi0.1O1.8 and C: Ce0.4Bi0.6O1.7
.
Scheme 1. The Knoevenagel condensation of benzaldehyde and diethyl malonate forming benzylidene malonate as the condensation product.

G. Varga et al. / Journal of Catalysis 381 (2020) 308–315
313
Table 3
For the above reactions, N2 atmosphere was needed; without it,
benzaldehyde (or its derivatives) was oxidised fast, thus, conden-
sation did not occur [48]. This observation gave the idea to include
oxidation in the catalytic test, the oxidation of toluene. If it works
producing benzaldehyde, we have one of the reactants for the Kno-
evenagel condensation. Since diethyl malonate should not get oxi-
dised, it can be added to the reaction mixture together with
toluene, and we now have the chance to create a domino reaction
system.
Recycling abilities of the Ce0.4Bi0.6O1.7 catalyst
results of the Knoevenagel condensation between benzaldehyde (1.0 eq) and diethyl
malonate (1.5 eq); mcat. = 0.02 g, T = 35 °C, t = 360 min, ethanol.
– conversion/TOF and selectivity
Recycling
Conversion (%)/TOF (molecules/basic sites/h)
Selectivity (%)
1st
100/9.0
99/8.4
100/8.4
98/7.8
100
94
93
2nd
3rd
4th
92
3.3. Testing the catalytic behaviour in the oxidation of toluene
For studying the oxidation behaviour of our substances,
solvent-free toluene oxidation was tried (Table 4). Initial experi-
ments made it clear that the single oxides (CeO2 and Bi2O3) did
not catalyse this reaction even at reflux temperature. The activity
Ce0.4Bi0.6O1.7 was negligible; however, the ceria-based one was
active; however, the Ce0.9Bi0.1O1.8 displayed appreciable activity
(11% conversion), and remarkable selectivity towards benzalde-
hyde (80%).
Testing different oxidising agents revealed that tert-butyl
hydroperoxide (TBHP) could only be applied. Other agents like
hydrogen peroxide or O2 gave no reaction (Table 5, lines 3 and
4). We tried to lower the reaction temperatures to get closer to
the temperature of the Knoevenagel reaction (Table 5, line 4),
and observed slightly lower activity at 60 °C than at reflux temper-
ature. On lengthening the reaction time at 60 °C, resulted in the
remarkable 42% conversion and 90% selectivity in a 24-h reaction
(Table 5, line 5). After this run, the catalyst was recycled three
times after regenerating it between the runs by filtering, washing
with water, then drying at 60 °C. It is shown in the last line of
Table 5 that more than 36% conversion of toluene was still main-
tained even after the third reuse of the catalyst. After the last
run, the structure of the catalyst was maintained verified by X-
ray diffractometry (Fig. 8).
The scope of the reaction was also studied using toluene deriva-
tives. It was observed that derivatives with electron donating sub-
stituent behaved similarly to toluene, while the presence of
electron withdrawing substituent prevented the oxidation to occur
(STable 6).
For the sake of the possible combination of the oxidation and
the condensation reaction, it had to be learnt if the oxidation pro-
ceeds in the presence of solvents used for the Knoevenagel reaction
or not. It was found that water could be a good solvent achieving
similar results to those obtained under solvent-free conditions;
however, in ethanol there was no oxidation at all (STable 7).
Fig. 7. The X-ray diffractograms of the as-prepared and the recycled Ce0.4Bi0.6O1.7
catalyst in the Knoevenagel condensation of benzaldehyde and diethyl malonate.
The original structure of the recycled Ce0.4Bi0.6O1.7 mixed oxide
was maintained even after the fourth recycling (Fig. 7).
The scope of the condensation reaction was also studied
(STable 5). As it is expected, the electron withdrawing groups in
the para position favour the reaction, since the carbonyl carbon
becomes more positive. However, the electron donating groups
do the opposite, consequently, the conversions decreased signifi-
cantly. Michael addition product was observed in these cases.
Malononitrile was as good active methylene compound as the
malonic ester, while malonic acid was useless in this reaction,
since acid-base reaction can take place with the basic catalyst,
and malonic acid deprotonated at the carboxylic group is not an
active methylene compound any more.
Table 4
Conversion/TOF and selectivity results of toluene oxidation with TBHP (mcat = 0.1 g,
T = 110 °C, t = 480 min, solvent-free).
3.4. Testing the catalytic behaviour in the toluene oxidation–
Knoevenagel condensation one-pot, domino reaction
Catalyst
CeO2
Conversion (%)/TOF (molecules/basic sites/h) Selectivity (%)
–
–
Ce0.9Bi0.1O1.8 11.0/51.0
Ce0.4Bi0.6O1.7 0.1/0.18
80
9
–
The combination of the two reactions provided over the
mixture of the two mixed oxides (0.1 g of Ce0.9Bi0.1O1.8 and 0.2 g
of Ce0.4Bi0.6O1.7) with nice results, when water was the solvent.
Bi2O3
–
Table 5
Effect of the oxidising agent – conversion/TOF and selectivity results of toluene oxidation over Ce0.9Bi0.1O1.8 catalyst; mcat = 0.1 g, solvent-free.
Oxidising agent
Temperature (°C)
Reaction time (min)
Recycling
Conversion (%)/TOF (molecules/basic sites/h)
Selectivity (%)
TBHP
O2
110
110
110
60
60
60
480
480
480
480
1440
1440
1440
1440
–
–
–
–
11/51.0
–
–
10/49.2
42/73.2
39/67.8
37/63.0
36/60.1
80
–
–
85
90
90
88
87
H2O2
TBHP
TBHP
TBHP
TBHP
TBHP
–
1st
2nd
3rd
60
60

314
G. Varga et al. / Journal of Catalysis 381 (2020) 308–315
Acknowledgements
This work was supported by the Hungarian Government and
the European Union through grant GINOP-2.3.2-15-2016-00013.
The financial helps are highly appreciated. One of us, G. Varga
thanks for the postdoctoral fellowship under the grant PD 128189.
Appendix A. Supplementary material
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.jcat.2019.11.011.
References
[1] E. Knoevenagel, Ueber eine darstellungsweise der glutarsäure, Ber. Dtsch.
Chem. Ges. 27 (1894) 2345–2346.
[2] A. Graul, J. Castaner, Atorvastatin calcium, Drugs Future 22 (1997) 956–968.
[3] L.R. Madivada, R.R. Anumala, G. Gilla, S. Alla, K. Charagondla, M. Kagga, A.
Bhattacharya, R. Bandichhor, An improved process for pioglitazone and its
pharmaceutically acceptable salt, Org. Process Res. Dev. 13 (2009) 1190–1194.
[4] T.J.N. Watson, S.W. Horgan, R.S. Shah, R.A. Farr, R.A. Schnettler, C.R. Nevill, F.J.
Weiberth, E.W. Huber, B.M. Baron, M.E. Webster, R.K. Mishra, B.L. Harrison, P.L.
Nyce, C.L. Rand, C.T. Goralski, Chemical development of MDL 103371: an N-
methyl-d-aspartate-type glycine receptor antagonist for the treatment of
stroke, Org. Process Res. Dev. 4 (2000) 477–487.
[5] G. Jenner, Steric effects in high pressure Knoevenagel reactions, Tetrahedron
Lett. 42 (2001) 243–245.
[6] N.E. Agafonov, I.P. Sedishev, A.V. Dudin, A.A. Kutin, G.A. Stashina, V.M. Zhulin,
Henry condensation under high pressure 2. Effect of aromatic aldehyde type
Fig. 8. The X-ray diffractograms of the as-prepared and the recycled Ce0.9Bi0.1O1.8
catalyst in the toluene oxidation reaction.
Table 6
Conversion and selectivity results of toluene oxidation to benzaldehyde–Knoevenagel
condensation of the in situ formed benzaldehyde and diethyl malonate one pot,
domino reaction over Ce0.9Bi0.1O1.8–Ce0.4Bi0.6O1.7 catalyst system (mcat.=(0.1 + 0.2) g,
T = 60 °C, t = 1440 min).
Toluene derivative
Solvent
Conversion
(%)*
Conversion
(%)**
Selectivity
(%)
and pressure on the yield of
x-nitrostyrenes and secondary processes, Bull.
Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.) 40 (1991) 366–372.
[7] G. Kaupp, M.R. Naimi-Jamal, J. Schmeyers, Tetrahedron 59 (2003) 3753–3760.
[8] D. Bogdal, Coumarins: Fast synthesis by knoevenagel condensation under
microwave irradiation, J. Chem. Res. (S) (1998) 468–469.
[9] P. Lidström, J. Tierney, B. Wathey, J. Westman, Microwave assisted organic
synthesis– a review, Tetrahedron 57 (2001) 9225–9283.
[10] J.R. Harjani, S.J. Nara, M.M. Salunkhe, Lewis acidic ionic liquids for the
synthesis of electrophilic alkenes via the Knoevenagel condensation,
Tetrahedron Lett. 43 (2002) 1127–1130.
[11] R.V. Hangarge, D.V. Jarikote, M.S. Shingare, Knoevenagel condensation
reactions in an ionic liquid, Green Chem. 4 (2002) 266–268.
4-Cl-toluene
4-NO2-toluene
4-HO-toluene
4-CH3-toluene
toluene
water
water
water
water
water
toluene
–
–
28
29
34
–
–
–
84
81
90
–
–
–
100
100
100
–
toluene
*
Conversion for toluene oxidation.
Conversion for Knoevenagel condensation.
**
[12] P. McNeice, A.C. Marr, P.C. Marr, M.J. Earle, K.R. Seddon, Binary alkoxide ionic
liquids, ACS Sustain. Chem. Eng. 6 (2018) 13676–13680.
[13] T. Murase, Y. Nishijima, M. Fujita, Cage-catalyzed Knoevenagel condensation
under neutral conditions in water, J. Am. Chem. Soc. 134 (2011) 162–164.
[14] X. Dong, Y. Hui, S. Xie, P. Zhang, G. Zhou, Z. Xie, Schiff base supported MCM-41
catalyzed the Knoevenagel condensation in water, RSC Adv. 3 (2013) 3222–
3226.
[15] B.C. Ranu, R. Jana, Ionic Liquid as Catalyst and Reaction Medium – A Simple,
Efficient and green procedure for Knoevenagel condensation of aliphatic and
aromatic carbonyl compounds using a task-specific basic ionic liquid, Eur. J.
Org. Chem. 16 (2006) 3767–3770.
The results obtained are displayed in Table 6. As it is shown, both
toluene and its derivatives with electron-donating substituent
worked well, provided with the desired condensation products in
high yields.
In this system, toluene oxidation took place first over the Bi(III)-
based catalyst, then the Knoevenagel condensation with diethyl
malonate as the active methylene compound followed. The consec-
utive reactions proceeded in water, an absolutely green solvent,
and was fully selective to the condensation product.
[16] X. Zhang, E.S.M. Lai, B. Martin-Aranda, K.L. Yeung, An investigation of
Knoevenagel condensation reaction in microreactors using
catalyst, Appl. Catal. A 261 (2004) 109–118.
a new zeolite
[17] J. Liang, Z. Liang, R. Zou, Y. Zhao, Heterogeneous catalysis in zeolites,
mesoporous silica, and metal-organic frameworks, Adv. Mater. 29 (2017)
1701139–1701159.
[18] F. Bigi, L. Chesini, R. Maggi, G. Sartori, Montmorillonite KSF as an inorganic,
water stable, and reusable catalyst for the Knoevenagel synthesis of coumarin-
3-carboxylic acids, J. Org. Chem. 64 (1999) 1033–1035.
4. Conclusions
[19] B.M. Choudary, M.L. Kantam, V. Neeraja, K.K. Rao, F. Figueras, L. Delmotte,
Layered double hydroxide fluoride: a novel solid base catalyst for C-C bond
formation, Green Chem. 3 (2001) 257–260.
[20] Y. Jia, Y. Fang, Y. Zhang, H.N. Miras, Y.F. Song, Classical Keggin intercalated into
layered double hydroxides: facile preparation and catalytic efficiency in
Knoevenagel condensation reactions, Chem. Eur. J. 21 (2015) 14862–14870.
[21] Y. Horiuchi, T. Toyao, M. Fujiwaki, S. Dohshi, T.H. Kim, M. Matsuoka, Zeolitic
imidazolate frameworks as heterogeneous catalysts for a one-pot P-C bond
formation reaction via Knoevenagel condensation and phospha-Michael
addition, RSC Adv. 5 (2015) 24687–24690.
The mixture of an exhaustively characterised Ce-based and Bi-
based BiCe oxide catalytic system proved to be suitable for promot-
ing a toluene oxidation benzaldehyde–benzaldehyde condensation
with diethyl malonate one-pot domino reaction system with 100%
selectivity towards the condensation product under mild condi-
tions and in water as the solvent. With this reaction system, many
of the requirements of green chemistry were met, such as the use
of recyclable heterogeneous catalysts, the application of an envi-
ronmentally absolutely benign solvent, reaching 100% selectivity
and running complex reaction in one pot, without the need for iso-
lating the intermediates.
[22] T. Li, H. Miras, Y.F. Song, Polyoxometalate (POM)-layered double hydroxides
(LDH) composite materials: design and catalytic applications, Catalysts
(2017) 260–276.
7
[23] A. Corma, V. Fornes, R.M. Martin-Aranda, F. Rey, Determination of base
properties of hydrotalcites: condensation of benzaldehyde with ethyl
acetoacetate, J. Catal. 134 (1992) 58–65.
[24] W. Zhou, M. Liu, Q. Zhang, Q. Wei, S. Ding, Y. Zhou, Synthesis of NiMo catalysts
supported on gallium-containing mesoporous Y zeolites with different gallium
contents and their high activities in the hydrodesulfurization of 4,6-
dimethyldibenzo-thiophene, ACS Catal. 7 (2017) 7665–7679.
Declaration of Competing Interest
The authors declared that there is no conflict of interest.

G. Varga et al. / Journal of Catalysis 381 (2020) 308–315
315
[25] K.R. Kloetstra, M. Van Laren, H. van Bekkum, Binary caesium–lanthanum oxide
supported on MCM- 41: a new stable heterogeneous basic catalyst, J. Chem.
Soc., Faraday Trans. 93 (1997) 1211–1220.
[37] A. Martinez-Arias, M. Fernandez-Garcia, L.N. Salamanca, R.X. Valenzuela, J.C.
Conesa, J.J. Soria, Structural and redox properties of ceria in alumina-
supported ceria catalyst supports, J. Phys. Chem. B 104 (2000) 4038–4046.
[38] J.R. McBride, K.C. Hass, B.D. Poindexter, W.H.J. Weber, Raman and X-ray
studies of Ce1ÀxRExO2Ày, where RE=La, Pr, Nd, Eu, Gd, and Tb, Appl. Phys. 76
(1994) 2435–2441.
[39] L. Baia, R. Stefan, J. Popp, S. Simon, W. Kiefer, Vibrational spectroscopy of
highly iron doped B2O3–Bi2O3 glass systems, J. Non-Cryst. Solids 324 (2003)
109–117.
[26] G. Postole, B. Chowdhury, B. Karmakar, K. Pinki, J. Banerji, A. Auroux,
Knoevenagel
condensation
reaction
over
acid–base
bifunctional
nanocrystalline CexZr1À xO2 solid solutions, J. Catal. 269 (2010) 110–121.
[27] P. Malik, D. Chakraborty, Bi (III)-catalyzed C-S cross-coupling reaction, Appl.
Organomet. Chem. 26 (2012) 557–561.
[28] M.F. Nizah, Y.H. Taufiq-Yap, U. Rashid, S.H. Teo, Z.S. Nur, A. Islam, Production of
biodiesel from non-edible Jatropha curcas oil via transesterification using
Bi2O3–La2O3 catalyst, Energy Conv. Manag. 88 (2014) 1257–1262.
[29] J. Liu, S. Zou, H. Wang, L. Xiao, H. Zhao, J. Fan, Synergistic effect between Pt(0)
and Bi2O3Àx for efficient room-temperature alcohol oxidation under base-free
aqueous conditions, Catal. Sci. Technol. 7 (2017) 1203–1210.
[30] L. Bourja, B. Bakiz, A. Benlhachemi, M. Ezahri, J.C. Valmalette, S. Villain, J.R.
Gavarri, J. Optoelectron. Adv Mater. – Symp. 3 (2011) 110–113.
[31] K. Sardar, H.Y. Playford, R.J. Darton, E.R. Barney, A.C. Hannon, D. Tompsett, J.
Fisher, R.J. Kashtiban, J. Sloan, S. Ramos, G. Cibin, R.I. Walton, Nanocrystalline
cerium-bismuth oxides: synthesis, structural characterization, and redox
properties, Chem. Mater. 22 (2010) 6191–6201.
[40] M. Subhadra, P. Kistaiah, Infrared and Raman spectroscopic studies of alkali
bismuth borate glasses: Evidence of mixed alkali effect, Vib. Spectrosc. 62
(2012) 23–27.
[41] R. Wang, H. Xu, X. Liu, Q. Ge, W. Li, Role of redox couples of Rh(0)/Rhd+ and
Ce4+/Ce3+ in CH4/CO2 reforming over Rh–CeO2/Al2O3 catalyst, Appl. Catal. A
305 (2006) 204–210.
[42] X. Luo, R. Wang, J. Ni, J. Lin, B. Lin, X. Xu, K. Wei, Effect of La2O3 on Ru/CeO2-
La2O3 catalyst for ammonia synthesis, Catal. Lett. 133 (2009) 382–387.
[43] Y. Ding, F. Yang, L. Zhu, N. Wang, H. Tang, Bi3+ self-doped NaBiO3 nanosheets:
facile controlled synthesis and enhanced visible light photocatalytic activity,
Appl. Catal. B 164 (2015) 151–158.
[32] L. Bourja, B. Bakiz, A. Benlhachemi, M. Ezahri, S. Villain, O. Crosnier, C. Favotto,
J.-R. Gavarri, Structural, microstructural and surface properties of a specific
CeO2–Bi2O3 multiphase system obtained at 600°C, J. Solid State Chem. 184
(2011) 608–614.
[44] N. Al-Haq, A.C. Sullivan, J.R.H. Wilson, Oxidation of alcohols using cerium (IV)
alkyl phosphonate modified silica, Tetrahedron Lett. 44 (2003) 769–771.
[45] P. Kustrowski, L. Chmielarz, E. Bozek, M. Sawalha, F. Roessner, Acidity and
basicity of hydrotalcite derived mixed Mg–Al oxides studied by test reaction of
MBOH conversion and temperature programmed desorption of NH3 and CO2,
Mater. Res. Bull. 39 (2004) 263–281.
ˇ
´
´
´
´
´
´
[33] M. Prekajski, Z. Dohcvic-Mitrovic, M. Radovic, B. Babic, J. Pantic, A. Kremenovic,
´
B. Matovic, Nanocrystaline solid solution CeO2–Bi2O3, J. Eur. Ceram. Soc. 32
(2012) 1983–1987.
[46] E.D. Bergmann, D. Ginsburg, R. Pappo, Organic Reactions, Vol. X, Wiley, New
York, 1959, p. 179.
[47] K.M. Parida, D. Rath, Amine functionalized MCM-41: an active and reusable
catalyst for Knoevenagel condensation reaction, J. Mol. Catal. A 310 (2009) 93–
100.
[34] F. Cao, Q. Dong, C. Li, J. Chen, X. Ma, Y. Huang, D. Song, C. Ji, Y. Lei,
Electrochemical sensor for detecting pain reliever/fever reducer drug
acetaminophen based on electrospun CeBiOx nanofibers modified screen-
printed electrode, Sens. Actuators B 256 (2018) 143–150.
[35] R. Hirani, C.A. Hogarth, Excitonic absorption in cerium phosphate glasses, J.
Mater. Sci. Lett. 8 (1989) 150–152.
[48] W.M.H. Sachtler, The mechanism of the catalytic oxidation of some organic
molecules, Catal. Rev. 4 (1971) 27–52.
[36] L. Li, B. Yan, CeO2–Bi2O3 nanocomposite: two-step synthesis, microstructure
and photocatalytic activity, J. Non-Cryst. Solids 355 (2009) 776–779.