An efficient Knoevenagel condensation of aldehydes with active methylene compounds over novel, robust CeZrO4?δ catalyst

Article abstract of DOI:10.1007/s11164-018-3587-6

Abstract: In the present work, we explored novel CeZrO_4?δ as a catalyst for Knoevenagel condensation of aldehydes with reactive methylene compounds like malononitrile and ethylcyanoacetate. For the present study, ceria, zirconia and CeZrO₄

Full text of DOI:10.1007/s11164-018-3587-6

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An efficient Knoevenagel condensation of aldehydes
with active methylene compounds over novel, robust
CeZrO42d catalyst
Amber J. Sahani1 • Anand S. Burange2 • Radha V. Jayaram1
Received: 16 June 2018 / Accepted: 31 August 2018
Ó Springer Nature B.V. 2018
Abstract
In the present work, we explored novel CeZrO4-d as a catalyst for Knoevenagel
condensation of aldehydes with reactive methylene compounds like malononitrile
and ethylcyanoacetate. For the present study, ceria, zirconia and CeZrO4-d were
prepared by gel combustion method and well characterized using XRD, SEM, EDX,
BET and TPD analyses, etc. A wide range of aldehydes were effectively condensed
over novel CeZrO4-d with reactive methylene compounds with high yields. In
addition, the CeZrO4-d was effectively reused for five consecutive cycles without
significant loss in its activity. To the best of our knowledge, this is the first liquid-
phase application of pure CeZrO4-d
.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11164-
18-3587-6) contains supplementary material, which is available to authorized users.
0
&
&
Anand S. Burange
anand.burange@wilsoncollege.edu
Radha V. Jayaram
rv.jayaram@ictmumbai.edu.in
1
2
Department of Chemistry, Institute of Chemical Technology, Matunga, Mumbai 400019, India
Department of Chemistry, Wilson College, Chowpatty, Mumbai 400007, India
123

A. J. Sahani et al.
Graphical abstract
Keywords MMOs Á Nanocatalysis Á Heterocyclic Á Heterogeneous catalysis Á
Nanostructures
Introduction
Knoevenagel condensation, which is one of the most important C–C bond formation
reactions, was reported for the first time in the 1890s by Knoevenagel [1, 2]. Various
C–C coupling reactions are reported [3, 4] and have great importance in the
syntheses of drug intermediates [5]. Typically, this reaction involves condensation
of reactive methylene compounds with carbonyl compounds. Among reactive
methylenes, b-dicarbonyls having pKa values between 9 and 11 can be easily
coupled with carbonyl compounds (aldehydes or ketones) [6].
Conventionally, Knoevenagel condensation is carried out in organic solvents like
ethanol, benzene and DMF using organic bases (like aliphatic amines, ammonium
salts, urea and amino acids) as catalysts [1]. Practically, it is quite difficult to reuse
or recycle these organic bases employed for the said condensation. In this context,
for economic viability and environmental concerns, there is a huge demand to avoid
use of bases for this reaction. Various inorganic solids as catalysts have been
reported so far for the Knoevenagel condensation. It mainly includes metal halides
[
[
[
[
7–9], metal oxides [10, 11], supported oxides [12–14], phosphates [15–18], zeolites
19], clays [20, 21], resins [22], amino-functionalized silica gel [23] and MCM-41
24]. Knoevenagel condensation is also well reported over Lewis acid and bases
7, 25–27] and also using solid-phase reactions [28, 29].
Recently, CeZrO4-d has been explored for conversion of ethylbenzene to styrene
30], whereas Pd-supported CeZrO4-d found catalytic application in Suzuki cross-
[
coupling in water [4] and CO oxidation [31]. To the best of our knowledge, so far,
no liquid-phase catalytic application of pure CeZrO4-d is reported.
1
23

An efficient Knoevenagel condensation of aldehydes with…
3
?
4?
Typically in ceria, cerium exists as a Ce /Ce (redox couple) [32]. Pure ceria
has a major drawback of sintering at elevated temperatures. Various mixed metal
oxides (MMOs) of ceria and zirconia have been explored in the past for catalytic
application [32, 33]. In the present work, by considering merits of cerium-based
materials, we explored novel CeZrO4-d as a catalyst for Knoevenagel condensation
reaction of aldehydes with reactive methylene compounds like malononitrile and
ethylcyanoacetate.
Experimental
General
In a 10-mL round-bottomed (RB) flask, benzaldehyde (0.106 g, 1.0 mmol),
malononitrile (0.078 mL, 1.1 mmol) and 5 mL of acetonitrile (ACN) was taken.
To this, 5 wt% of the catalyst CeZrO4-d was added and the mixture was heated to
80 °C. Progress of the reaction was monitored by thin layer chromatography (TLC).
At the end of the reaction, the reaction mixture was cooled to room temperature and
the catalyst was recovered by filtration method. The filtrate was dried over Na SO
2
4
(
anhydrous) and the solvent evaporated under vacuum. The crude product was
purified using column chromatography with ethyl acetate and petroleum ether
mixture as eluent. The Knoevenagel condensation products were further confirmed
by physical constants, FT-IR, GC–MS and NMR data.
Synthesis of CeZrO42d
CeZrO4-d was synthesized from nitrates of cerium and zirconium by gel
combustion method using glycine as a fuel. In a typical synthesis, metal nitrates
and glycine were added to distilled water and the solution was further heated on a
hot plate to dryness to obtain a gel. The obtained gel on further heating yielded a
powder which on calcination at 600 °C for 6 h gave CeZrO4-d
.
Results and discussion
The prepared CeZrO4-d was well characterized by X-ray diffraction (XRD),
Brunauer–Emmett–Teller (BET), scanning electron microscopy (SEM), transmis-
sion electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDX)
analyses. The ceria and zirconia were also synthesized by the same method and well
characterized. The XRD pattern of CeZrO4-d shows six distinct peaks (Fig. 1a) at
2
9.1°, 33.6°, 48.5°, 57.6°, 71.2° and 78.5° for (111), (200), (220), (311), (400) and
331) facets, respectively, attributed to a fluorite structure. The surface topography
(
of the materials was also compared using SEM. The ceria (Fig. 1b), zirconia (refer
to Supplementary Information) and CeZrO4-d (Fig. 1c, d) showed a porous nature
which is clearly seen in SEM analysis. The pore size distribution and surface area
were further analyzed using a BET surface area analyzer. The surface area and pore
size distribution are given below in Table 1.
123

A. J. Sahani et al.
Fig. 1 Characterization of ceria and CeZrO4-d: a XRD of CeZrO4-d; b SEM of ceria; c, d SEM images
of CeZrO4-d
Table 1 BET surface area of pore size distribution of prepared samples
2
Surface area (m /g)
Entry
Material
Pore volume (cc/g)
1
2
3
CeO
ZrO
CeZrO4-d
2
36
22
30
0.16
0.12
0.17
2
The elemental composition of CeZrO4-d sample was determined via EDX
technique. The EDX results obtained for the said sample were found to be in
accordance with the expected input concentration (Refer to Supplementary
Information: Fig. 5).
The surface acidity of CeZrO4-d sample was evaluated using ammonia
temperature-programmed desorption (NH –TPD; see Supplementary Information:
3
Fig. 7). NH –TPD of CeZrO
3
shows two major peaks at * 160 and at * 360 °C
4-d
corresponding to weak and strong acidic sites, respectively.
The initial studies were carried out using benzaldehyde and malononitrile over
CeZrO4-d (5 wt%) as a model reaction (Scheme 1). Initially, the reaction was
carried out in ACN solvent at various temperatures for 3 h (Table 2). A significant
1
23

An efficient Knoevenagel condensation of aldehydes with…
Scheme 1 Knoevenagel condensation of benzaldehyde and malononitrile over CeZrO4-d catalyst (model
reaction)
Table 2 Temperature and solvent study
a
Entry
Temperature (°C)
Solvent
% Conversion
1
2
3
4
5
6
7
8
R.T.
60
70
80
80
80
80
80
80
ACN
48
71
83
94
93
96
95
09
49
ACN
ACN
ACN
Ethanol
DMSO
DMF
Toluene
Methanol
1
0
Reaction conditions: benzaldehyde (1 mmol), malononitrile (1.1 mmol), catalyst: CeZrO4-d (5 wt%),
reaction time (3 h)
a
%
Conversion was determined using gas chromatography
enhancement in percent conversion was observed with increase in the reaction
temperature. A maximum reaction conversion of 94% for the said reaction was
obtained at 80 °C (Table 2, entry 4), while at room temperature (30 °C), only 48%
conversion was observed (Table 2, entry 1). Over ceria and zirconia (5 wt%) at
8
0 °C in ACN, the lowest conversion was observed, as compared to CeZrO4-d.
To know the effect of solvents on Knoevenagel condensation, we screened
various polar protic, aprotic and non-polar solvents at the optimized reaction
temperature (80 °C). More than 90% conversion was achieved in case of DMF,
DMSO, EtOH and ACN (Table 2, entries 4–7). Among these four solvents, we
carried out our further optimization studies using ACN as a solvent; very little
conversion was observed in case of non-polar solvent toluene (Table 2, entry 8) for
the said reaction.
After solvent and temperature optimization, we checked the effect of malonon-
itrile mole ratio on percent conversion. For initial studies, we retained the
benzaldehyde-to-malononitrile ratio as 1:1.1. Maximum (96%) conversion was
obtained with a benzaldehyde-to-malononitrile ratio of 1:2.
The effect of catalyst loading also has a profound effect on activity. We
employed various loadings of a catalyst for the said conversion. With the increase
123

A. J. Sahani et al.
Table 3 Effect of malononitrile concentration and catalyst loading on Knoevenagel condensation
a
Entry
Malononitrile concentration (mmol)
Catalyst loading (wt%)
% Conversion
1
2
3
4
5
6
7
1.1
1.5
2.0
2.0
2.0
2.0
1.1
5
5
94
94
5
96
1
50
3
66
10
10
100
98
Reaction conditions: benzaldehyde (1 mmol), reaction time 3 h, CeZrO catalyst4-d
a
%
Conversion was determined using gas chromatography
from 1 to 5% loading, increase in a percent conversion was observed, while no
significant increase in conversion was observed above 5% (Table 3).
In order to test the efficacy and robustness of the set protocol for Knoevenagel
condensation, we tested various carbonyl compounds with malononitrile (Table 4).
Since there was no observable difference in % conversion after changing
malononitrile concentration, we performed substrate studies using malononitrile
with 1.1 mmol. With 1.1 mmol of malononitrile, 98% conversion was achieved
with 10 wt% catalyst loading (Table 3, entry 7), while with 2.0 mmol of
malononitrile over 10 wt% catalyst, conversion was 100% (Table 3, entry 6).
Upon time optimization, 100% conversion with 1.1 mmol of malononitrile with
1
0 wt% catalyst loading was obtained in 3.5 h.
For substrate scope, the reaction was carried out at 80 °C with 10 wt% of catalyst
loading with 1.1 mmol of malononitrile for 3.5 h (Table 4). The yields for electron-
donating (–OMe, –NMe and –OH)-substituted benzaldehydes were above 90%
2
(Table 4, entries 1, 4, 5 and 16). Electron-withdrawing groups are known to
facilitate condensation reactions. In our case, comparative yields of corresponding
products were observed in case of deactivating groups like –NO and –Br (Table 4,
2
entries 3, 7 and 8).
The protocol was also evaluated for heterocyclic aldehydes like 2-thiophenecar-
boxaldehyde and 3-thiophenecarboxaldehyde, and upon reaction with malononitrile,
produced yields of 86 and 75% respectively (Table 4, entries 10 and 13). In a
nutshell, the set catalytic protocol was found efficient to condense carbonyl
compounds with electron-donating, electron-withdrawing and heterocyclic car-
bonyls with malononitrile as well as ethylcyanoacetate (Table 4, entries 2 and 14)
with comparable yields of condensation products.
Typically, on ceria-zirconia-based materials, both acidic as well as basic sites are
present [40]. In solid solutions, the ratio of acidic and basic sites is found to be a key
factor for enhancement of the catalytic activity [40]. Thus, the activity in ceria-
zirconia materials depends upon the acidic as well as basic sites, whereas CeZrO4-d
has anionic vacancies [4] which may also affect the activity for the Knoevenagel
condensation. The surface acidity of CeZrO4-d, evaluated by ammonia-TPD (well
1
23

An efficient Knoevenagel condensation of aldehydes with…
Table 4 Substrate scope
Sr.
No.
Reactant
Product
Yield a
M.P.
(°C)
References
[35]
[35]
[35]
CN
CN
O
1
94
148
85-86
200
MeO
MeO
OMe
OMe
2b
O
CN
COOEt
9
9
6
0
3
[35]
CN
CN
O
4
5
9
8
180
N
N
[
35]
36]
CN
CN
O
114–115
9
9
5
5
MeO
MeO
[
CN
CN
6
7
O
85
[36]
Br
Br
CN
CN
O
9
0
107
[
36]
36]
CN
CN
O
8
9
8
8
9
5
162
Br
Cl
Br
[
CN
CN
O
163–164
Cl
123

A. J. Sahani et al.
Table 4 continued
Sr.
No.
Reactant
Product
Yield a
M.P.
(°C)
References
[37]
1
0
8
6
70
CN
CN
[37]
O
1
1
1
2
9
8
0
5
130
128
NC
[
38]
39]
CN
CN
O
[
CN
CN
O
1
3
7
5
63
S
S
[
40]
40]
CN
1
4b
O
98
9
9
4
0
COOEt
NC
NC
NC
[
CN
CN
O
1
5
6
155
[40]
CN
CN
1
O
9
2
197
HO
HO
Reaction condition aldehyde (1 mmol), malononitrile (1.1 mmol), catalyst: CeZrO4-d (10 wt%), solvent
ACN), temperature (80 °C), time (3.5 h)
Square brackets []: literature reference for corresponding product
(
a b
Isolated yield; 1,3-ethylcyanoacetate (1.1 mmol) was used instead malononitrile
discussed in the catalyst characterization part) is found to be a key factor for the
Knoevenagel condensation reaction.
We separated the catalyst after each run and washed it with methanol to remove
adhered organic impurities. We found the catalyst reusable for the five consecutive
cycles without noteworthy loss in the catalytic activity. Thus, the reusability of the
catalyst and substrate compatibility makes the protocol interesting.
1
23

An efficient Knoevenagel condensation of aldehydes with…
Conclusion
In conclusion, in continuation of work in the catalysis arena [41, 42], we have
explored the novel cerium-zirconium-based material CeZrO4-d as an effective
catalyst for Knoevenagel condensation reaction. The catalytic protocol was found to
be effective for condensing malononitrile and ethylcyanoacetate with various
carbonyls bearing electron-donating and electron-withdrawing groups. The protocol
was also found effective for condensation of heterocyclic carbonyls with
malononitrile. To the best of our knowledge, this is the first liquid-phase application
of pure CeZrO4-d material and we strongly believe that it can be a potential
substitute for other Ce–Zr-based oxide materials.
Acknowledgements We are grateful to Prof. A. K. Tyagi and Dr. Rakesh Shukla, Bhabha Atomic
Research Centre, India, for their support in the present work.
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