Novel iron doped calcium oxalates as promising
heterogeneous catalysts for one-pot multi-
component synthesis of pyranopyrazoles†
Kranthi Kumar Gangu, Suresh Maddila, Surya Narayana Maddila
and Sreekantha B. Jonnalagadda
*
The co-precipitation method using a surface modifier, glutamic acid was employed in the design of iron
doped calcium oxalates (Fe-CaOx). Fe-CaOx with diverse iron loading (0.5–3.0 mmol) were prepared
and their phase purity and surface features were examined by X-ray powder diffraction (XRD), Fourier
transform infrared (FT-IR), electron microscopy (SEM, TEM), energy dispersive X-ray (EDX), Inductively
Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), N
2
-sorption, thermal and fluorescent
analysis. The Fe-CaOx materials proved excellent as catalysts in the one-pot syntheses of eight 2,4-
dihydro pyrano[2,3-c]pyrazole derivatives via four component condensation of aromatic aldehydes,
malononitrile, hydrazine hydrate and dimethyl acetylenedicarboxylate in ethanol with impressive yields
(92–98%) in short reaction times (<20 min). The 2.0 mmol loaded iron in Fe-CaOx showed the finest
catalytic performance with 98% yield in 10 min compared to other loadings. The stability, ease of
separation, and reusability for up to six cycles of Fe-CaOx make it an environmentally friendly and cost-
effective viable choice for the value-added organic transformations.
1 Introduction
A large number of publications in the eld of catalysis endorse
that a wide range of heterogeneous materials meet several green
chemistry criteria as catalysts.
1–3
Many such eco-friendly and
sustainable catalysts are valuable in making various efficacious
value-added organic transformations feasible.
4,5
Calcium
oxalate, Ca(C
2
O
4
) is a natural and widely available common
organic mineral in carbonate concretions, and in sediments of
lake and marine, lignite and hydrothermal veins.
6–9
The bio-
minerals of calcium oxalates are abundantly found in vegeta-
tion as their crystals are a prime cause for urolithiasis.
10
Calcium oxalates (CaOx) exist mainly in three forms (mono, di
and tri-hydrate) and the calcium oxalate monohydrate (COM),
CaC
2
O
4
$H
2
O is the prominent entity relative to the other two
forms, calcium oxalate di-hydrate (COD), CaC
2
O
4
$2H
2
O and tri-
hydrate (COT), CaC
2
O
4
$3H
2
O.
11–13
The monoclinic crystal
system of COM is thermodynamically most stable phase
compared to COD (tetragonal, metastable) and COT (triclinic,
unstable).
14
The unique properties of COM such as extremely
low water solubility and high thermal stability grab the atten-
tion of researchers. Verganelaki et al., have prepared
a nanocomposites by mixing the amorphous silica and calcium
oxalate nanoparticles for strengthening of building materials.
15
Due to enhanced physico-chemical affinities and compatibility
with natural stone and the crack free nature, such nano-
composites are widely used in the improvement of physical
characteristics of constructing materials, i.e. tensile strength
and hygric properties. The thermal stability, surface area,
mechanical strength and tunable textural properties of CaOx
prompt their utility as catalyst support material for many cata-
lytically active metal centres.
The ability to hold the adsorbed substances rmly and
thereby activate the reactants is the advantageous characteristic
of transition metals.
16,17
The incorporation of transition metals
into the solid support lattices is common practice to enhance
their activity and to improve cost-effectiveness. Relative to other
expensive choices, iron is the most possible candidate for
doping due to its low cost, abundance, non-toxic and environ-
mentally benign nature.
18
The partial loading of iron in the
place of Ca
2+
in CaOx can give rise to material with improved
activity. Besides the chemical composition, the physical
features attained by the catalysts such as morphology, size etc.
are known to play a key role in their activity.
19–21
The controlled
morphology and growth of crystals with ideal physical features
is prime initiative to augment the catalytic activity. Literature
survey reveals that many biological proteins, amino acids,
surfactants, polymeric compounds have shown signicant
inuence on crystal growth and morphology of several materials
of interest under diverse synthetic conditions.
22–25
School of Chemistry & Physics, University of KwaZulu-Natal, Westville Campus,
Chiltern Hills, Durban-4000, South Africa. E-mail: jonnalagaddas@ukzn.ac.za; Fax:
+27 31 2603091; Tel: +27 31 2607325
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c6ra25372e
Cite this: RSC Adv.,2017,7,423
Received 17th October 2016
Accepted 16th November 2016
DOI: 10.1039/c6ra25372e
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Multi-component reaction (MCR), where all reactants (more
than two) placed in one vessel and make the reaction conditions
viable for developing bonds between the reactants to give a single
product is an eco-compatible synthetic technique and which is
replacing many traditional tardy processes. The MCR is a worth-
while approach for the preparation of varied organic scaffolds
with introduction of diverse precursor elements.
26–28
Heterocyclic
systems are prevalent in nature and possess unique characteris-
tics to design varied physiological and pharmacologically active
substrates.
29
Heterocyclic compounds are integral parts of the
medicinal chemistry and have played a pragmatic role as
precursor materials in the synthesis of drugs possessing anti-
malarial, antiulcer, diuretic, anthelmintic, antidepressants,
anticancer, antineoplastic and antipsychotic activities.
30–33
The
wide range of physico-chemical and biological properties
instilled in the heterocyclic compounds open new vistas in the
scheming of novel pharmaceutical materials with impressive
bioactivities. Among heterocycles, pyrazoles in general and pyr-
anopyrazoles in particular possess salient pharmaceutical and
biological characteristics with wide adoption in the eld of
medicinal chemistry, which necessitates competent procedures
for their syntheses.
34–38
Literature shows that Zonouz et al. have
prepared the pyrano[2,3-c]pyrazole derivatives with different
substituted aldehydes under reux at 60
C with 64–78% yields
and reaction time of 2.5 h.
39
Zou et al. have synthesized pyrano
[2,3-c]pyrazoles moieties using ethyl acetoacetate in the place of
dimethyl acetylenedicarboxylate reactant and reported products
with 72–85% of yield in 2.5–5.0 h reaction time at 50
C.
40
Tam-
addon and Alizadeh reported the synthesis of dihydropyrano[2,3-
c]pyrazoles compounds, with combination of aryl aldehyde,
malononitrile, ethyl acetoacetate and hydrazine hydrate in water
at 50–60
C by using cocamidopropyl betaine (CAPB), a zwitter-
ionic biodegradable surfactant as catalyst with yields of 88–
96%.
41
Soleimani et al. have synthesized different pyranopyrazole
derivatives at 70
C by using nanostructured Fe
3
O
4
@SiO
2
as
catalyst with 83–94% yield in 20–40 min reaction time.
42
In earlier
work, we have reported the efficacy use of some heterogeneous
catalysts and their activity in selective synthesis of heterocyclic
compounds with excellent yields.
43–46
In the present study, a series of novel Fe-CaOx materials were
prepared by co-precipitation method using glutamic acid as
crystal growth modier. The efficacies of the materials as
heterogeneous catalyst for the synthesis of pyranopyrazole
moieties through four-component one-pot reaction were
investigated. The effect of varied Fe doping, morphological and
textural features on their activity was probed.
2 Experimental
2.1 Materials preparation
All required chemicals were acquired and used without any
further purication. Calcium chloride (CaCl
2
), disodium oxalate
(Na
2
C
2
O
4
) and iron nitrate nonahydrate (Fe(NO
3
)
3
$9H
2
O) were
purchased from Sigma Aldrich. Glutamic acid was from Fluka
chemicals. All aromatic aldehydes, malononitrile, hydrazine
hydrate and dimethyl acetylenedicarboxylate were purchased
from Sigma Aldrich. Millipore-Q puried water was used
throughout the experiment.
Fe-CaOx with four doping levels of iron was prepared by co-
precipitation method. Initially, the stock solutions of precursors
of 0.5 M of CaCl
2
, 0.2 M of Na
2
C
2
O
4
and 0.5 M of Fe(NO
3
)
3
$9H
2
O
were prepared. In a typical preparation, 5.0 mmol (10 mL of 0.5
M) of CaCl
2
and 2.0 mmol (0.330 g) of glutamic acid were mixed
with 50.0 mL water with continuous stirring. To that solution,
5.0 mmol (25 mL of 0.2 M) of Na
2
C
2
O
4
was added slowly from
burette and the resultant mixture was further stirred for 30 min.
A solution containing requisite amount of iron precursor was
added drop by drop to the mixture and stirring was continued
for another 3 h. The reaction mixture was le overnight (12 h) to
facilitate the crystallisation and the resultant crystalline mate-
rial was harvested by centrifugation followed by several wash-
ings with millipore water. Repeating the exercise, total four
materials namely, 0.5 mmol Fe-CaOx/glu (0.5 Fe-CaOx/glu),
1.0 mmol Fe-CaOx/glu (1.0 Fe-CaOx/glu), 2.0 mmol Fe-CaOx/
glu (2.0 Fe-CaOx/glu) and 3.0 mmol Fe-CaOx/glu (3.0 Fe-CaOx/
glu) were synthesised. The collected samples were calcined at
350
C over 3 h under air ow. For comparison, un-doped CaOx
in presence and absence of glutamic acid (glu) was prepared
following the same procedure and designated as CaOx/glu and
CaOx, respectively. The calculated chemical compositions of the
samples and obtained yields are summarised in Table 1. The
materials were further analysed to conrm their characteristics.
2.2 Characterization
For phase identications, the X-ray diffraction analysis was
conducted using a Bruker D8 advance diffractometer with Ni
ltered Cu Ka radiation (V ¼ 45 kV, I ¼ 40 mA). The XRD pattern
was collected in a 2q range of 20 to 70
with scan rate of 4
min
1
and a step size of 0.02
. FT-IR analysis was conducted on
Perkin Elmer (Spectrum 100, USA) over a range of 4000 to 400
cm
1
at resolution of 4 cm
1
for investigating the vibrational
modes existing in the materials. Microscopic analysis such as
Table 1 Chemical composition of samples
Sample CaCl
2
(mmol) Na
2
C
2
O
4
(mmol) Fe(NO
3
)
3
$9H
2
O Glutamic acid (mmol) Yield (%)
CaOx 5.0 5.0 ——79
CaOx/glu 5.0 5.0 — 2.0 85
0.5 Fe-CaOx/glu 5.0 5.0 0.5 mmol (1.0 mL of 0.5 M iron sol.) 2.0 84
1.0 Fe-CaOx/glu 5.0 5.0 1.0 mmol (2.0 mL of 0.5 M iron sol.) 2.0 87
2.0 Fe-CaOx/glu 5.0 5.0 2.0 mmol (4.0 mL of 0.5 M iron sol.) 2.0 94
3.0 Fe-CaOx/glu 5.0 5.0 3.0 mmol (6.0 mL of 0.5 M iron sol.) 2.0 92
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FESEM (Zeiss Ultra Plus, Germany) operating at 5–20 kV and
HRTEM (JEOL 1010, Japan) with accelerating voltage of 100 kV
was conducted to know the morphological changes and crystal
size identication. All samples were coated with an Au lm to
get a good resolution for FESEM. The identication and
conrmation of elements including iron was done by elemental
analysis through EDX (AZtec soware, Oxford instruments, UK)
unit attached to FESEM and ICP-OES (Optima 5300 DV, USA).
For textural characteristics such as surface area and pore
properties, N
2
adsorption/desorption analysis was conducted at
77 K using Micromeritics Tristar-3020, USA. For N2 sorption
studies, all samples were degassed overnight at 150
Cto
eliminate the unwanted gases on the surfaces of samples. The
mass loss with respect to temperature and thermal stability of
materials were identied with the TG analysis using SDT Q600
instrument at heating rate of 10
C min
1
under nitrogen gas
ow. Fluorescence spectra of samples were obtained by Perkin
Elmer LS-55 uorescence spectrophotometer at room temper-
ature.
1
H-NMR,
15
N,
13
C spectra of organic products were ob-
tained using Bruker advance 400 spectrometer at ambient
temperature conditions.
3 Results and discussion
3.1 X-ray diffraction and FT-IR analysis
For the phase identication, crystallinity and crystallite size, the
X-ray diffraction studies were conducted. The Fig. 1 shows the
XRD patterns of samples and the X-ray analysis conrmed the
formation of COM phase. The powder diffraction database was
used for the phase identication, which revealed that the XRD
patterns of all samples well matched with the COM phase (PDF
20-0231).
47
The identied peaks projected at d ¼ 5.83, 3.60, 2.94,
2.47, 2.33, 2.25, and 2.06
˚
A corresponding to COM crystal, were
assigned to (101), (020), (202), (112), (130), (202), (321) lattice
planes, respectively. The doping of iron into the COM lattice did
not create any new phase, conrming that iron occupied the
interstitial position of COM crystals (Fig. 1c–f). The observed
variation in the peak intensities, which impact on the crystal-
linity of the samples, can be attributed to the effect of glutamic
acid used and percentage of Fe doped.
48
The crystallinity was tested using X'Pert High score plus
soware aer successive prole t treatments, which indicates
that the degree of crystallinity of the material decreases with
increase in doping of Fe in CaOx. The control sample without
the glutamic acid (Fig. 1a) recorded high degree of crystallinity
(62 4.2%), but when glutamic acid used (Fig. 1b), the crys-
tallinity dropped to 51 3.5% and the trend continued with
increased Fe in the samples (Fig. 1c–f). The results show that
introduction of glutamic acid as crystal growth modier has
worked well towards the control of nucleation. The crystallite
size was determined by the Scherrer's formula using (020)
reection as reference and the resultant calculations showed
that the crystallite size reduced in presence of glu to 32–38
4 nm, relative to the control sample (CaOx) with crystallite size
of 52 2.6 nm. The XRD studies also reveal that the glutamic
acid concentration inhibits crystal growth and inuence
morphological features, but not altering the thermodynamically
stable COM phase.
FT-IR spectroscopic method was used to analyse the vibra-
tional frequencies of COM phases. The presence of hydroxyl
group, metal to oxygen bond and carboxylic group absorption
bands conrm the COM phase formation (Fig. 2). Absence of
any glutamic acid related peaks reveal that glu was involved in
the crystal growth inhibition, and does not bind to the surfaces
of COM crystals. The FT-IR spectra also reveal that added glu-
tamic acid is suited to retain the more stable COM phase with
crystal growth inhibition, but hampering the formation of less
stable COD and COT phases.
The hydroxyl absorption bands appeared at 3337 and 3433
cm
1
respectively correspond to symmetric and asymmetric
Fig. 1 XRD patterns (a) CaOx (b) CaOx/glu (c) 0.5 Fe-CaOx/glu (d) 1.0
Fe-CaOx/glu (e) 2.0 Fe-CaOx/glu (f) 3.0 Fe-CaOx/glu.
Fig. 2 XRD patterns (a) CaOx (b) CaOx/glu (c) 0.5 Fe-CaOx/glu (d) 1.0
Fe-CaOx/glu (e) 2.0 Fe-CaOx/glu (f) 3.0 Fe-CaOx/glu.
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O–H stretching vibrations, whereas 3254 and 3058 cm
1
corre-
spond to stretching vibrations of O–H–O. The peaks at 1610
(asymmetric) and 1317 cm
1
(symmetric) stretching vibrations
are from the carboxylic group. The peaks at 662 and 517 cm
1
are related to the bending (rocking) vibrational frequencies of
the same group. The absorption peak at 781 cm
1
represents
the existence of metal to oxygen bond.
49,50
3.2 Surface morphology and particle size analysis by FESEM
and HRTEM
The microscopic analysis gives an insight into the morpholog-
ical changes, shape and size of COM particles taken place due to
crystal growth modier, glutamic acid in the synthesis. In the
absence of glutamic acid, in control experiments, COM was in
spherical shape with aggregated particles in the range between
250–400 nm (Fig. 3a and c). In presence of glutamic acid,
generated regular shaped particles and COM particles were
needle shaped and spread uniformly over the surface. Some
hexagonal shaped particles were also observed (Fig. 3b), which
were due to the elongation of spherical shaped particles in CaOx
sample. The surface capping ability of glutamic acid promotes
the structural modication and reduction in the particle size. A
perusal of the TEM micrograph of CaOx/glu (Fig. 3d) shows that
in presence of glu, particle size decreased to 180–210 nm.
The materials with different concentrations of Fe, from 0.5
Fe-CaOx/glu to 3.0 Fe-CaOx/glu, (Fig. 4) exhibited identical
morphology with no signicant changes, but particles showed
some differences in their shape. The TEM micrograph of 0.5 Fe-
CaOx/glu (Fig. 5a) shows particles with needle-like ends, which
changed to irregular sharped ends with 1.0 Fe-CaOx/glu
(Fig. 5b). While the 2.0 Fe-CaOx/glu (Fig. 5c) exhibited
hexagonal shaped particles with semi ellipsoid shapes and
particle size 108–238 nm, the 3.0 Fe-CaOx/glu (Fig. 5d) showed
an over dispersion of iron particles with their hexagonal shapes
deteriorated and particle size remaining unaltered. With
increase in iron content, the distortions in the shape of COM
particles were noticed. The elemental analysis conducted using
EDX and ICP-OES conrmed the presence of iron and its
anticipated increment in wt% from sample 0.5 to 3.0 Fe-CaOx,
authenticate the synthetic procedure employed (Fig. 5).
3.3 The effect of doped iron on CaOx substrate:
thermogravimetric, textural characteristics and uorescent
emission analysis
The effective doping of iron into the lattices of CaOx induces the
diverse variations in their properties. In order to examine the
thermal stability of the samples, the TG analysis was conducted.
The TGA curves of CaOx/glu, 1.0 Fe-CaOx/glu and 3.0 Fe-CaOx/
glu indicate that the weight loss occurred in three steps and
% weight loss is lower for the higher Fe-doped sample (Fig. 6).
In all three samples, the rst decomposition step starts at
110
C and ended about 180–230
C with wt loss of 5.0% for
CaOx/glu and 12.5% each for 1.0 Fe-CaOx/glu and 3.0 Fe-CaOx/
glu, which represents the dehydration of samples. The an-
hydrated samples decomposed to CaCO
3
with evolution of CO
in the second step at around 450–500
C (wt loss of 20.5% in all
cases). In the third step, the further decomposition of CaCO
3
to
CaO by loss of CO
2
occurred between 650–800
C with wt loss of
30.0% for CaOx/glu, 25.0% for 1.0 Fe-CaOx/glu and 18.0% for
3.0 Fe-CaOx/glu. The lower weight loss in the third step recor-
ded with increase in Fe loading suggests that the higher
concentration of doped-iron replaces, the calcium ions and
Fig. 3 SEM micrographs of (a) CaOx (b) CaOx/glu; TEM micrographs of (c) CaOx (b) CaOx/glu.
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thereby the quantity of decomposed CaO is reduced. The TG
analysis reveals the COM phase formation
51
as well as success-
ful doping of iron into the lattices of COM crystals and their
good thermal stability.
The textural properties of the materials were measured with
N
2
adsorption isotherm at 77 K. The observed isotherms are
related to the type IV and the amount of probe N
2
gas adsorbed
varied with samples (Fig. 7). The BET-specic surface area was
measured and the value increased from control to highest
dopant loaded sample (Table 2). The CaOx (control) recorded
low BET-surface of 9.93 m
2
g
1
, whereas high iron containing
3.0 Fe-CaOx/glu possessed high BET-surface area (93.22 m
2
g
1
).
The pore volume also increased in the same trend as BET-
surface area. As the dopant concentration increased, the
Fig. 4 SEM micrographs of (a) 0.5 Fe-CaOx/glu (b) 1.0 Fe-CaOx/glu (c) 2.0 Fe-CaOx/glu (d) 3.0 Fe-CaOx/glu.
Fig. 5 TEM micrographs of (a) 0.5 Fe-CaOx/glu (b) 1.0 Fe-CaOx/glu (c) 2.0 Fe-CaOx/glu (d) 3.0 Fe-CaOx/glu; elemental analysis by EDX and
ICP-OES.
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