Calcium ferrite, an efficient catalyst for knoevenagel condensation(A green approach)

Article abstract of DOI:10.13005/ojc/330418

Calcium ferrite NPs catalyst have been used as a cheaper and highly efficient catalyst for Knoevenagel condensation of active methylene substrate with various carbonyl compounds affording condensed products in excellent yields in shorter reaction time. Th

Full text of DOI:10.13005/ojc/330418

ISSN: 0970-020 X
CODEN: OJCHEG
017, Vol. 33, No. (4):
Pg.1736-1743
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
2
www.orientjchem.org
Calcium ferrite, an efficient catalyst for knoevenagel
condensation(A green approach)
PARVEEN PIPPAL and PRABAL PRATAP SINGH*
Department of Chemistry, GLA University, 17 km stone, NH-2 Delhi-Mathura highway,
Chaumuhan Mathura, 281406 (U.P.) India.
*
Corresponding author Email: prabal.singh@gla.ac.in
http://dx.doi.org/10.13005/ojc/330418
(Received: May 25, 2017; Accepted: July 07, 2017)
ABSTRACT
Calcium ferrite NPs catalyst have been used as a cheaper and highly efficient catalyst for
Knoevenagel condensation of active methylene substrate with various carbonyl compounds affording
condensed products in excellent yields in shorter reaction time. The developed greener protocol is
very simple, involving cleaner work up and the synthesized products do not require further purification.
The catalyst can easily be removed and reused at least for four times without any appreciable change
in reactivity.
Keywords: Knoevenagel condensation; Calcium ferrite; Ethylcyanoacetate; Malononitrile;
Reusable catalyst.
2
4
INTROꢀUCTION
hydrotalciteinionicliquids ,mesoporousorganosilica
25
supported potassium carbonate (BPMO-IL-KCO ) ,
UiO-66-NH2 . In addition, there are certain reports
on the use of electrochemical induced, microwave
and ultra sound irradiation methods for Knoevenagel
. Recently nano particles like
BaAl O3 , Fe O @SiO , P4VP/Al O -SiO
Nitridated KCC-1 , amine functionalized PAN ,
Pd(0) has been reported to catalyze the
Knoevenagel condensation reaction. Various
3
26
Knoevenagel condensation is a very useful
reaction in organic chemistry known for its synthetic
utility in carbon carbon bond formation and their
enormous applications particularly in fine chemicals
1
2
27-28
condensation
3
-5
29
30
31
and therapeutic and pharmacological products
.
,
2
3
4
3
2
2
3
2
2
33
The condensation reaction is generally performed
by using stoichiometric or catalytic amounts of
ammonia, primary and secondary amines, pyridine,
3
4
6
7-10
11
12
35-37
piperadine dimethylamino
Al O , SmI3
,
,
MOF
has also been tried to catalyze the above
2
3
1
3
14
15
16
17
CdCl2 , LaCl , ZnCl2 , Zeolite , ZnCl -SiO
reaction. However these methods suffer from
disadvantages such as unsatisfactory yields, long
reaction times, stoichiometric amount of catalyst,
harsh reaction conditions, use of hazardous
3
4
2
1
8
19
20
fluorapatite , hydroxyapatite , metal oxides , ionic
2
1
22
liquids like [Bmim]Cl.xAlCl3 , [MMIm][MSO ] ,
4
2
3
ethylenediammonium diacetate in ionic liquids ,

1737
PIPPAL & SINGH, Orient. J. Chem., Vol. 33(4), 1736-1743 (2017)
solvents, non recoverable catalyst that contains GeneralprocedureforKnoevenagelcondensation
toxic metals, moisture sensitive nature of catalyst reaction (3a-m)
and tedious work up procedure. Therefore there is
To a well stirred reaction mixture of
a great need to design and develop a protocol that aldehyde (1mmol) and active methylene compound
does not have the above problems.Here in this paper (1mmol), in 10 mL methanol, the calcium ferrite
we report a greener approach towards synthesis of (5 mmol%) catalyst was added and refluxed for the
Knoevenagel condensation products using a highly requisite period of time.The progress of reaction was
efficient, cheaper, reusable, biocompatible and monitored by TLC. On completion of the reaction
environment friendly heterogeneous nano catalyst the catalyst was removed with the help of external
yielding the products in good to excellent yields magnet. The supernatant liquid was decanted and
in shorter reaction times. The developed protocol reaction mixture was concentrated on vacuum
involves cleaner and easier work up procedure rotary evaporator to obtain crude material which was
reducing the use of hazardous solvents.
then recrystalized using EtOAc: hexane mixtures.
In general, no further purification was required for
solid product. However for liquid mixture, the crude
product was purified by column chromatography
over silica gel (100-200 mesh size) to get the pure
MATERIALS ANꢀ METHOꢀS
Experimental
General information
1
13
compound.All products were characterized H & C
All the solvents and reagents were used NMR spectroscopy, Mass and FTIR spectroscopy
as such as supplied from commercial sources. The (See electronic supporting information).The
recorded melting points are uncorrected. IR spectra recovered catalyst was further used to check its
were recorded in KBr on a Schimadzu FTIR 8401 number of recyclability and efficacy.
spectrometer and Perkin Elmer version10.03.06 for
1
13
the liquid samples. H and C spectra were recorded Characterization of catalyst
on a Bruker DRX 300 spectrometer operating at
The XRD spectrum of CaFe O nano
2
4
1
13
3
00 MHz for H NMR and 75 MHz for C NMR as particle is presented in Fig.1 showing the lattice and
solutions in CDCl and DMSOd . The ESI mass structural parameters of catalyst.
3
6
spectra were measured on waters UPLC-TDQ
spectrometer. TLC was performed on silica coated
The morphology of the nano particle
glass plate, spots were developed in I Chamber was investigated using SEM analysis (Fig 2). The
2
or visualized in UV chamber. SEM was recorded micrograph reveals that the particles are elongated
at Technai G2 30S TWIN at 300KV accelerating agglomerated having uneven size and distribution.
voltage. Powder X-Ray Diffraction (PXRD) pattern Agglomeration may be due to the magnetic dipole
was recorded on Hecus X-Ray Systems S3 Model
using Cu Ka radiation (k = 1.5404 A) from 0-10°.
Preparation of calcium ferrite NPs catalyst
In a typical procedure for the synthesis
of catalyst the mixture of calcium carbonate
(
(
1 equiv), sugar (17 equiv), Fe (NO ) .9H O
2 3 3 2
2 equiv), monoethanolamine (25 equiv), HNO (44
3
equiv) and double distilled water (300 mL) in a beaker
was heated on hot plate up to the dryness. The
black residue obtained was kept in preheated muffle
furnace at 800 ± 10 °C for 6-7 hours. The resulting
brown colored powder was further characterized by
XRD (Fig.1), SEM (Fig. 2) and FTIR (Fig. 3) in order
to determine their formation, size and morphological
behavior.
Fig. 1: Powder X-ray diffraction pattern of
sample

PIPPAL & SINGH, Orient. J. Chem., Vol. 33(4), 1736-1743 (2017)
1738
interaction between ferrite particles. The particles
have large number of voids due to release of gaseous
products. The size of the particles ranges from
be assigned to the stretching vibration frequency of
Fe-O bands.
100-150 nm.
Catalytic activity
In connection with our enduring interest
concerning the investigation of new heterogeneous
CaFe O nano catalyst, we here in report a highly
effective and economic protocol for Knoevenagel
condensation using calcium ferrite catalyst in
methanol as a solvent (Scheme 1). The strategy
was then applied for the condensation of various
aldehydes and active methylene compounds to yield
knoevenagel products.
The FT-IR absorption spectrum of sample
0
calcinated at 800 C for 4 h in presented in Fig.
2
4
-
1
3
Strong absorption bands at 670 and 478 cm can
CaFe O
4
Ph
H
CN
CN
CN
CN
2a
2
PhCHO +
MeOH/reflux
1a
3a
Scheme 1
Fig. 2: SEM micrographs at different magnifications (A-C)
Fig. 3: FT-IR spectrum of synthesized CaFe O NPs
2
4

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PIPPAL & SINGH, Orient. J. Chem., Vol. 33(4), 1736-1743 (2017)
Table 1: Screening of catalysts for
Knoevenagel condensation product
RESULT ANꢀ ꢀISCUSSION
In our preliminary study, benzaldehyde
1a was treated with malononitrile 2a in presence
of various catalysts taking methanol as solvent
(Table 1). The expected knoevenagel condensed
product 2-benzylidenemalononitrile 3a could not
be isolated even in trace amount in absence of
catalyst (Table 1, entry 1). It was observed that
CaFe O NPs catalyzed reaction completed within
Entry
Catalysta
Time (min)
Yieldsb
1
2
3
4
5
6
7
8
No catalyst
120
120
120
120
120
120
120
20
NP
NP
NP
15
10
20
25
95
Fe O4
2
SrFe O4
2
ZnO@Fe O4
2
CuFe O4
2
2
4
ZnFe O4
20 min. to give the product 3a in 95% yield (Table 1,
entry 8). However other catalysts viz; Fe O and
2
MgSO4
2
4
CaFe O4
SrFe O could not initiate the reaction even after
2
2 4
prolonged refluxing (Table 1, entries 2-3), where a
Reaction conditions: benzaldehyde (1mmol); few catalysts were able to generate 3a in very less
malononitrile (1mmol); methanol 10mL; reflux yields (Table 1, entries 4-7).
a
b
Isolated yields
Inspiring by the above results we then tried
to optimize the reaction condition by treating 1a
Table 2: Solvent effects on the reaction of 1a
with 2a under calcium ferrite as catalyst
and 2a with CaFe O NPs using different solvents
2
4
(
such as toluene, xylene, water, ethanol, acetonitrile
Entry
Solventa
Time (min) Yield (%)b
and DMF). The results are shown in Table 2. The
yields of the products for reaction in presence of
toluene, xylene, water, acetonitrile and DMF as
solvent were lower than that of observed in methanol
at refluxing condition (Table 2, entry 2). Although
ethanol gave comparable yield (Table 2, entry 4).
1
2
3
4
5
6
Toluene
MeOH
MeCN
EtOH
DMF
Water
120
20
50
95
60
92
40
65
60
20
60
120
a
Reaction conditions: benzaldehyde (1mmol);
malononitrile (1mmol);
CaFe O (10 mmol%); refluxing temperature;
2
4
b
Isolated yields
Table 3: Study of catalyst loading on the
Knoevenagel condensation
Entry
Catalyst (mol %)a
Yield (%)b
1
2
3
4
5
6
7
1
2
3
5
10
15
20
40
65
70
80
95
94
94
Scheme 2. A plausible mechanism for
Knoevenagel condensation reaction of
benzaldehyde and malononitrile over
CaFe O NPs catalyst
a
Reaction conditions: benzaldehyde (1mmol);
malononitrile (1mmol);
b
time 20 min;methanol reflux: Isolated yields
2
4

PIPPAL & SINGH, Orient. J. Chem., Vol. 33(4), 1736-1743 (2017)
1740
Table 4. Knoevenagel condensation of various aldehydes and active methylene compounds in
presence of calcium ferrite NPs.
Ar
CN
CaFe O (10 mol%)
2 4
CN
ArCHO +
a-m
EWG
H
EWG
MeOH/Reflux
1
2a-m
3a-m
Entry
1
Ar
EWG
Time (min)
Product
Ph CN
Yields (%)
95
12
Ph
Ph
-CN
H
CN
CN
3
a
b
Ph
H
8
0
2
3
-CO Et
2
35
30
CO Et
2
3
MeO
CN
CN
4-OMePh
-CN
85
H
3c
MeO
OMe
CN
CN
4
5
3,4-OMePh
2,5-OMePh
90
85
-
-
CN
40
40
H
3
d
OMe
CN
CN
CN
MeO
MeO
H
3e
OMe
CN
6
3
,4-OMePh
-CO Et
2
45
84
H
CO Et
2
3f
O N
2
CN
CN
9
6
7
4-NO
2
Ph
-CN
-CN
10
30
H
3
g
CN
CN
9
1
2
-NO Ph
2
O N
2
8
H
3
h

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PIPPAL & SINGH, Orient. J. Chem., Vol. 33(4), 1736-1743 (2017)
O N
2
CN
7
8
9
1
4-NO Ph
2
-CO Et
2
45
45
H
CO Et
2
3
i
Cl
H
CN
CN
0
2-ClPh
-CN
75
3j
HN
CN
CN
8
5
1
1
3-Indolyl
4-PhCHO
-CN
-CN
35
10
H
3k
H
CN
CN
CN
12
95
NC
H
3l
OH
H
CN
CN
1
3
2-OHPh
-CN
40
80
3m
aIsolated yields
Interestingly calcium ferrite nano particle
catalyzed reactions were found to be very clean
and the products were obtained in extremely pure
crystalline form with an average yield of 80-96%. All
the reactions were completed in very less time of 10-
45 minutes. Under the optimized reaction condition
the generality of the protocol was investigated
with various aromatic and indolyl aldehydes with
different active methylene substrates. The results
are summarized in Table 4.
Calcium ferrite MNPs catalysed reactions
werefoundtobeverycleanandtheproductsobtained
in pure crystalline form while aliphatic condensed
Fig. 4: Recyclability of CaFe O MNPs catalyst
2
4
To study the effect of catalyst loading, the products were viscous oily and were purified by
knoevenagel condensation was carried out with passing through column chromatography.
varying amount of catalyst taking the model reaction
(
Scheme 1).The desired product was found to show
In general, knoevenagel condensation
the best yields at 10 mmol% of the catalyst (Table 3, reactions of various carbonyl compounds with
entry 5). While excess of the catalyst loading could malononitrile were faster (Table 4, entries 1,3-
not improve the yield further (Table 3, entries 6-7).
5,7-8 and 10-13) than ethylacyanoacetate (Table

PIPPAL & SINGH, Orient. J. Chem., Vol. 33(4), 1736-1743 (2017)
1742
4
, entries 2,6 and 9). This may be attributed to
The plausible mechanism for the formation
of the products (3a-m) has been shown in scheme 2.
It is assumed that Ca NPs facilitate the knoevenagel
type coupling by co-ordinating to oxygen of carbonyl
groups. Also Ca NPs can activate malononitrile or
ethylcyanoacete so that deprotonation occurs. As a
consequence knoevenagel condensation proceeds
by activation of reactants by Nano particles.
the strong electron withdrawing nature of nitrile
groups compared to ester group.However reactions
involving aldehydes bearing electron withdrawing
groups were faster and high yielding (Table 4,
entries 7-10) as compared to electron donating
groups (Table 4, entries 1-6). The procedure was
successfully applied to various substituted aromatic
aldehydes with malononitrile and ethylcyanoacetate
(
2
Table 4).The ether (entries 3-6) and esters (entries
,6 and 9) linkages in aromatic aldehydes were
CONCLUSION
remain unaffected in warmer alcoholic conditions.
Heteroaromatic aldehyde also gave 3k in very good
with malononitrile (Table 4, entry 11). The reaction
was further investigated for the synthesis of p-bis-
The synthesized calcium ferrite MNPs act
as heterogeneous catalyst that may be practical
alternate for application of knovenagel reaction in
the view of the following advantages a) high catalytic
activity under milder condition, b) easier and cleaner
external magnetic separation, c) waste minimization
without any side reaction, d) use of non-toxic and
inexpensive catalyst, e) reusability of catalyst, d)
biocompatibility and environmental friendly catalyst
2-(phenylidene)malononitrile by the condensation of
terephthaldehyde with two moles of malononitrile to
afford the desired product 3l in 95% yield.(Table 4,
entry 12).
2+
Reusability of catalyst
due to presence of Ca instead heavy metal.
Interestingly we have noteworthy examined
the recovery and reuse of the catalyst (Fig 4). After
the product formation, the catalyst was recovered
with the help of strong external magnet and the
supernatant liquid was decanted. The catalyst was
washed with excess of methanol, dried in oven for 4 h
and finally used for further runs.The heterogeneous
CaFe O MNPs substantially demonstrated the ability
Supporting Information
For analytical/spectral data see the
attached supporting file.
ACKNOꢁLEꢀGEMENTS
Authors sincerely thanks Vice Chancellor
of GLA University for the financial support and infra
structure.
2
4
to retain its catalytic activity even for four cycles
Figure 4.
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