Novel iron doped calcium oxalates as promising heterogeneous catalysts for one-pot multi-component synthesis of pyranopyrazoles

Article abstract of DOI:10.1039/c6ra25372e

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), N₂-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.

Full text of DOI:10.1039/c6ra25372e

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Novel iron doped calcium oxalates as promising
heterogeneous catalysts for one-pot multi-
component synthesis of pyranopyrazoles†
Cite this: RSC Adv., 2017, 7, 423
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), N2-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.
Received 17th October 2016
Accepted 16th November 2016
DOI: 10.1039/c6ra25372e
www.rsc.org/advances
a nanocomposites by mixing the amorphous silica and calcium
oxalate nanoparticles for strengthening of building materials.15
1 Introduction
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 Ca2+ 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 signicant
inuence on crystal growth and morphology of several materials
of interest under diverse synthetic conditions.22–25
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(C2O4) 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),
CaC2O4$H2O is the prominent entity relative to the other two
forms, calcium oxalate di-hydrate (COD), CaC2O4$2H2O and tri-
hydrate (COT), CaC2O4$3H2O.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
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
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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 deriꢀvatives with different
substituted aldehydes under reux 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
2 Experimental
2.1 Materials preparation
All required chemicals were acquired and used without any
further purication. Calcium chloride (CaCl2), disodium oxalate
(Na2C2O4) and iron nitrate nonahydrate (Fe(NO3)3$9H2O) 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 puried 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 CaCl2, 0.2 M of Na2C2O4 and 0.5 M of Fe(NO3)3$9H2O
were prepared. In a typical preparation, 5.0 mmol (10 mL of 0.5
M) of CaCl2 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 Na2C2O4 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 conrm their characteristics.
ꢀ
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 Fe3O4@SiO2 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 modier. 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.
2.2 Characterization
For phase identications, 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 70ꢀ with scan rate of 4ꢀ
minꢁ1 and a step size of 0.02ꢀ. FT-IR analysis was conducted on
Perkin Elmer (Spectrum 100, USA) over a range of 4000 to 400
cmꢁ1 at resolution of 4 cmꢁ1 for investigating the vibrational
modes existing in the materials. Microscopic analysis such as
Table 1 Chemical composition of samples
Sample
CaCl2 (mmol)
Na2C2O4 (mmol)
Fe(NO3)3$9H2O
Glutamic acid (mmol)
Yield (%)
CaOx
CaOx/glu
0.5 Fe-CaOx/glu
1.0 Fe-CaOx/glu
2.0 Fe-CaOx/glu
3.0 Fe-CaOx/glu
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
—
—
—
79
85
84
87
94
92
2.0
2.0
2.0
2.0
2.0
0.5 mmol (1.0 mL of 0.5 M iron sol.)
1.0 mmol (2.0 mL of 0.5 M iron sol.)
2.0 mmol (4.0 mL of 0.5 M iron sol.)
3.0 mmol (6.0 mL of 0.5 M iron sol.)
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FESEM (Zeiss Ultra Plus, Germany) operating at 5–20 kV and not create any new phase, conrming that iron occupied the
HRTEM (JEOL 1010, Japan) with accelerating voltage of 100 kV interstitial position of COM crystals (Fig. 1c–f). The observed
was conducted to know the morphological changes and crystal variation in the peak intensities, which impact on the crystal-
size identication. All samples were coated with an Au lm to linity of the samples, can be attributed to the effect of glutamic
get a good resolution for FESEM. The identication and acid used and percentage of Fe doped.48
conrmation of elements including iron was done by elemental
The crystallinity was tested using X'Pert High score plus
analysis through EDX (AZtec soware, Oxford instruments, UK) soware aer successive prole t treatments, which indicates
unit attached to FESEM and ICP-OES (Optima 5300 DV, USA). that the degree of crystallinity of the material decreases with
For textural characteristics such as surface area and pore increase in doping of Fe in CaOx. The control sample without
properties, N2 adsorption/desorption analysis was conducted at the glutamic acid (Fig. 1a) recorded high degree of crystallinity
77 K using Micromeritics Tristar-3020, USA. For N2 sorption (62 ꢂ 4.2%), but when glutamic acid used (Fig. 1b), the crys-
studies, all samples were degassed overnight at 150 ꢀC to tallinity dropped to 51 ꢂ 3.5% and the trend continued with
eliminate the unwanted gases on the surfaces of samples. The increased Fe in the samples (Fig. 1c–f). The results show that
mass loss with respect to temperature and thermal stability of introduction of glutamic acid as crystal growth modier has
materials were identied with the TG analysis using SDT Q600 worked well towards the control of nucleation. The crystallite
ꢁ1
ꢀ
instrument at heating rate of 10 C min under nitrogen gas size was determined by the Scherrer's formula using (020)
ow. Fluorescence spectra of samples were obtained by Perkin reection as reference and the resultant calculations showed
Elmer LS-55 uorescence spectrophotometer at room temper- that the crystallite size reduced in presence of glu to 32–38 ꢂ
1
ature. H-NMR, 15N, 13C spectra of organic products were ob- 4 nm, relative to the control sample (CaOx) with crystallite size
tained using Bruker advance 400 spectrometer at ambient of 52 ꢂ 2.6 nm. The XRD studies also reveal that the glutamic
temperature conditions.
acid concentration inhibits crystal growth and inuence
morphological features, but not altering the thermodynamically
stable COM phase.
3 Results and discussion
3.1 X-ray diffraction and FT-IR analysis
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 conrm 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.
For the phase identication, 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 conrmed the
formation of COM phase. The powder diffraction database was
used for the phase identication, which revealed that the XRD
patterns of all samples well matched with the COM phase (PDF
20-0231).47 The identied 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
The hydroxyl absorption bands appeared at 3337 and 3433
cmꢁ1 respectively correspond to symmetric and asymmetric
assigned to (ꢁ101), (020), (ꢁ202), (112), (130), (202), (321) lattice
planes, respectively. The doping of iron into the COM lattice did
Fig. 1 XRD patterns (a) CaOx (b) CaOx/glu (c) 0.5 Fe-CaOx/glu (d) 1.0 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.
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 cmꢁ1 corre- hexagonal shaped particles with semi ellipsoid shapes and
spond to stretching vibrations of O–H–O. The peaks at 1610 particle size 108–238 nm, the 3.0 Fe-CaOx/glu (Fig. 5d) showed
(asymmetric) and 1317 cmꢁ1 (symmetric) stretching vibrations an over dispersion of iron particles with their hexagonal shapes
are from the carboxylic group. The peaks at 662 and 517 cmꢁ1 deteriorated and particle size remaining unaltered. With
are related to the bending (rocking) vibrational frequencies of increase in iron content, the distortions in the shape of COM
the same group. The absorption peak at 781 cmꢁ1 represents particles were noticed. The elemental analysis conducted using
the existence of metal to oxygen bond.49,50
EDX and ICP-OES conrmed 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).
3.2 Surface morphology and particle size analysis by FESEM
and HRTEM
3.3 The effect of doped iron on CaOx substrate:
thermogravimetric, textural characteristics and uorescent
emission analysis
The microscopic analysis gives an insight into the morpholog-
ical changes, shape and size of COM particles taken place due to
crystal growth modier, glutamic acid in the synthesis. In the
absence of glutamic acid, in control experiments, COM was in The effective doping of iron into the lattices of CaOx induces the
spherical shape with aggregated particles in the range between diverse variations in their properties. In order to examine the
250–400 nm (Fig. 3a and c). In presence of glutamic acid, thermal stability of the samples, the TG analysis was conducted.
generated regular shaped particles and COM particles were The TGA curves of CaOx/glu, 1.0 Fe-CaOx/glu and 3.0 Fe-CaOx/
needle shaped and spread uniformly over the surface. Some glu indicate that the weight loss occurred in three steps and
hexagonal shaped particles were also observed (Fig. 3b), which % weight loss is lower for the higher Fe-doped sample (Fig. 6).
were due to the elongation of spherical shaped particles in CaOx In all three samples, the rst decomposition step starts at
sample. The surface capping ability of glutamic acid promotes 110 ꢀC and ended about 180–230 ꢀC with wt loss of 5.0% for
the structural modication and reduction in the particle size. A CaOx/glu and 12.5% each for 1.0 Fe-CaOx/glu and 3.0 Fe-CaOx/
perusal of the TEM micrograph of CaOx/glu (Fig. 3d) shows that glu, which represents the dehydration of samples. The an-
in presence of glu, particle size decreased to 180–210 nm.
hydrated samples decomposed to CaCO3 with evolution of CO
The materials with different concentrations of Fe, from 0.5 in the second step at around 450–500 ꢀC (wt loss of 20.5% in all
Fe-CaOx/glu to 3.0 Fe-CaOx/glu, (Fig. 4) exhibited identical cases). In the third step, the further decomposition of CaCO3 to
morphology with no signicant changes, but particles showed CaO by loss of CO2 occurred between 650–800 ꢀC with wt loss of
some differences in their shape. The TEM micrograph of 0.5 Fe- 30.0% for CaOx/glu, 25.0% for 1.0 Fe-CaOx/glu and 18.0% for
CaOx/glu (Fig. 5a) shows particles with needle-like ends, which 3.0 Fe-CaOx/glu. The lower weight loss in the third step recor-
changed to irregular sharped ends with 1.0 Fe-CaOx/glu ded with increase in Fe loading suggests that the higher
(Fig. 5b). While the 2.0 Fe-CaOx/glu (Fig. 5c) exhibited 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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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.
thereby the quantity of decomposed CaO is reduced. The TG varied with samples (Fig. 7). The BET-specic surface area was
analysis reveals the COM phase formation51 as well as success- measured and the value increased from control to highest
ful doping of iron into the lattices of COM crystals and their dopant loaded sample (Table 2). The CaOx (control) recorded
good thermal stability.
low BET-surface of 9.93 m2 gꢁ1, whereas high iron containing
The textural properties of the materials were measured with 3.0 Fe-CaOx/glu possessed high BET-surface area (93.22 m2 gꢁ1).
N2 adsorption isotherm at 77 K. The observed isotherms are The pore volume also increased in the same trend as BET-
related to the type IV and the amount of probe N2 gas adsorbed surface area. As the dopant concentration increased, the
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Fig. 8 Fluorescent spectra of (a) un-doped CaOx (b) 1.0 Fe-CaOx/glu
(c) 2.0 Fe-CaOx/glu (d) 3.0 Fe-CaOx/glu.
Fig. 6 TGA curves of (a) CaOx/glu (b) 1.0 Fe-CaOx/glu (c) 3.0 Fe-
CaOx/glu.
Fig. 8 shows the uorescent spectra of CaOx crystals with
different iron doping. When samples were excited at 250 nm,
the emission maximum was exhibited at 756 nm. The emission
intensity diminished with increase in doping of iron. The
decrease in uorescence intensity is reveals that the Fe is
substituted in some of the places of Ca2+ ions in crystal struc-
ture and this conrms the entry of iron into the lattice of CaOx.
Relative to the un-doped CaOx, the doped iron decreases the
uorescence efficiency of the sample through ion–ion interac-
tions and energy transfer processes. The doped iron in the
crystal structure quenches the uorescence intensity of CaOx
crystals by weakening of the interactions between Ca2+ and
oxalate ions.
3.4 Catalytic activity of Fe-CaOx
Fig. 7 N2 adsorption/desorption isotherms at 77 K.
Aer characterization of the materials, their potential as
heterogeneous catalysts was tested in the synthesis of pyrano
[2,3-c]pyrazole derivatives via one-pot four component conden-
sation reaction. To evaluate the catalytic efficiencies of Fe-CaOx,
with varied doping of iron, the typical reaction (Scheme 1)
involved equimolar ratios of 3-uoro benzaldehyde (1.0 mmol),
malononitrile (1.0 mmol), hydrazine hydrate (1.0 mmol) and
dimethyl acetylene dicarboxylate (1.0 mmol) in ethanol and
chosen catalyst. The four reactants and 20 mg of the catalyst
were allowed to reux at 50 ꢀC in ethanol. Aer conrming the
number of additional adsorptive sites increase and thereby the
surface area also improve. Pore size is in mesoporous range
with high value for CaOx/glu sample and low for the 3.0 Fe-
CaOx. The increased surface area and pore volume with
dopant concentration divulges that the dopant replaces the
calcium ions in its crystal lattice, but creates more pores of
lesser size without blocking the existing pores.
Table 2 Textural features from N2 sorption and XRD analysis
BET-surface
area (m2 gꢁ1
Pore volume
(cm3 gꢁ1
Pore size
(nm)
Average crystallite
size (nm) from XRD
Sample
)
)
CaOx
CaOx/glu
0.5 Fe-CaOx/glu
1.0 Fe-CaOx/glu
2.0 Fe-CaOx/glu
3.0 Fe-CaOx/glu
9.9 ꢂ 1.2
13.5 ꢂ 0.9
31.3 ꢂ 1.8
46.3 ꢂ 3.3
49.2 ꢂ 2.0
93.2 ꢂ 2.1
0.03 ꢂ 0.005
0.05 ꢂ 0.003
0.09 ꢂ 0.002
0.12 ꢂ 0.003
0.13 ꢂ 0.002
0.14 ꢂ 0.001
17.5 ꢂ 1.14
19.3 ꢂ 1.01
13.5 ꢂ 1.94
12.3 ꢂ 2.01
12.7 ꢂ 1.05
6.9 ꢂ 1.98
52 ꢂ 2.6
32 ꢂ 3.1
36 ꢂ 5.3
34 ꢂ 2.8
33 ꢂ 3.3
38 ꢂ 4.2
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Scheme 1 Typical reaction ((1) 3-fluoro benzaldehyde, (2) malanonitrile, (3) hydrazine hydrate, (4) dimethyl acetylenedicarboxylate).
completion of reaction with TLC examination, the reaction due over dispersion of iron on the surfaces of CaOx as evidenced
mixture was ltered with suction pump and ensured the sepa- from the TEM micrograph (Fig. 4d). The change in basic
ration of catalyst for the recycling purposes. The organic structural orientation of CaOx crystals under higher Fe condi-
product from the ltrate was extracted with ethyl acetate and tions could be the likely the reason behind the poor catalytic
recovered aer removal of solvent under vacuum. The product performance of 3.0 Fe-CaOx/glu. The optimally Fe doped
was washed several times with ethanol to afford pure product. sample, (2.0 Fe-CaOx/glu) facilitated completing the reaction in
The structure of organic product was conrmed by the analysis excellent yields and shorter reaction time.
1
of using varied spectral data including H, 15N, and 13C-NMR
Aer selecting the appropriate catalyst among the four, the
(Fig. S2–S4†). The 1H signals observed at d 3.64, 7.09 and requirement of amount of catalyst (2.0 Fe-CaOx/glu) to ease the
13.81 ppm respectively indicated the presence of methoxy organic reaction was investigated by varying it from 10 to 50 mg
(–OCH3), amino (–NH2) and secondary amine (–NH) protons (Table S1†). A perusal of the results indicate that while amount
and presence of amino group further is conrmed by 15N <20 mg took longer time and lower yields, the increase in
spectrum.
amount does not enhance the yield or reduce the reaction time.
Spectral data of methyl 6-amino-5-cyano-4-(3-uorophenyl)- Further, to examine the efficacy of 2.0 Fe-CaOx/glu as catalyst,
2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylate.
Mp:
203– a series of reactions were conducted using ve different
205 ꢀC; 1H NMR (400 MHz, DMSO-d6) 3.64 (s, 3H, OCH3), 4.80 (s, substituted aldehydes under optimized conditions. All the
1H, CH), 6.95 (d, J ¼ 7.16 Hz, 2H, ArH), 7.02 (t, J ¼ 15.32 Hz, 1H, reactions gave the respective pyrano[2,3-c]pyrazole moieties in
ArH), 7.09 (s, 1H, NH2), 7.33 (d, J ¼ 6.52 Hz, 1H, ArH), 13.81 (s, good to excellent yields (91–98%) (Table 4).
1H, NH). 13C NMR (100 MHz, DMSO-d6): 15.04, 36.60, 51.72,
Based the experimental results and identied products,
57.17, 60.88, 103.38, 113.36, 113.57, 113.98 (4JCF ¼ 18.32 Hz), a plausible reaction mechanism is proposed in Scheme 2. The
114.20 (2JCF ¼ 23.21 Hz), 120.07, 123.42 (6JCF ¼ 3.4 Hz), 128.87 catalyst initiates the formation of benzylidine malononitrile
(5JCF ¼ 3.8 Hz), 130.12, 130.20 (1JCF ¼ 5.3 Hz), 147.66, 147.73, intermediate (3) through the Knoevenagel condensation of
155.25, 158.28, 160.21, 160.72 (3JCF ¼ 245.27 Hz), 163.14; 15N aldehyde (1) and malononitrile (2), while hydrazine hydrate (4)
NMR (40.55 MHz, DMSO-d6) d 7.09 (s, 2H, NH2); FT-IR;- 3422, combine with dimethyl acetylenedicarboxylate (5) to give pyr-
3291, 3177, 2199 1722, 1602, 1489, 1316, 1186.
azolone intermediate (6). The Michael addition between (3) and
To establish the need of catalyst, the un-catalysed title (6) followed by cyclization on the catalyst surface produces the
reaction was conducted under similar reaction conditions. The desired pyranopyrazole moiety selectively.
reaction took 2.5 h to produce the nal product with 60% yield.
Table 3 Catalytic performance of samplesa
Initially, when NaOH, Na2CO3, pyridine, AcOH, or Al2O3 were
employed as catalysts, no signicant improvement was found
either in the reaction time or yield (Table 3, entries 2–5). The
addition of CaOx/glu reduced the reaction time, but produced
the low yields (Table 3, entry 6). Thereaer, the reaction was
examined with different Fe-CaOx/glu samples (0.5 Fe-CaOx/glu,
1.0 Fe-CaOx/glu, 2.0 Fe-CaOx/glu, 3.0 Fe-CaOx/glu) to compare
their efficacy in getting better yields of pyrano[2,3-c]pyrazole in
shorter reaction times. When 0.5 Fe-CaOx/glu was employed as
catalyst, the reaction was nished in 15 min with yield of 89%,
whereas 1.0 Fe-CaOx/glu gave 93% yield in 15 min. When 2.0 Fe-
CaOx/glu was used as catalyst, the reaction was completed in
10 min and recorded 98% yield. Surprisingly, the use of 3.0 Fe-
CaOx/glu resulted in lower yield (90%) and longer reaction time
(20 min) (Table 3, entry 9). The higher amount of iron in 3.0 Fe-
CaOx might have hindered the creation of active catalytic sites
Entry
Catalyst
Reaction time (min)
Yield (%)
1
2
3
Without catalyst
NaOH
Na2CO3
150
110
110
95
60
63
68
71
70
79
89
93
98
90
4
AcOH
5
Al2O3
80
6
CaOx/glu
50
7
8
9
10
0.5 Fe-CaOx/glu
1.0 Fe-CaOx/glu
2.0 Fe-CaOx/glu
3.0 Fe-CaOx/glu
15
15
10
20
a
Reaction conditions: 3-uoro benzaldehyde (1.0 mmol), malononitrile
mmol), hydrazine hydrate (1.0 mmol), dimethyl
(1.0
acetylenedicarboxylic acid (1.0 mmol), catalyst (20 mg) and ethanol
(5.0 mL) were reuxed at 50 ꢀC. Isolated yields.
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Table 4 List of synthesis of pyrano[2,3-c]pyrazole moiety with different substituted aromatic aldehydes with 2.0 Fe-CaOx/glu as catalystab
Entry Aldehyde Product Yield (%) Time (min)/mp
1
94
10/236–237 ꢀ
C
C
2
95
15/245–247 ꢀ
3
91
15/213–215 ꢀ
C
4
96
10/217–218 ꢀ
C
5
6
93
92
10/258–260 ꢀ
C
C
15/198–200 ꢀ
7
94
15/221–223 ꢀ
C
a
Reaction conditions: substituted benzaldehyde (1.0 mmol), malononitrile (1.0 mmol), hydrazine hydrate (1.0 mmol), dimethyl
acetylenedicarboxylate (1.0 mmol) 2.0 Fe-CaOx/glu and ethanol (5.0 mL) were reuxed at 50 ꢀC. b Isolated yields.
The reusability was investigated for 2.0 Fe-CaOx/glu with title was dried under vacuum for 1 h at 60 ꢀC and tested for the
reaction (Scheme 1) to estimate the feasibility to use the catalyst recyclability. The catalytic performance was not altered in terms
for the successive reactions. The ltered and separated catalyst of reaction time and yields up to six cycles. Aer the sixth cycle,
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Scheme 2 Plausible mechanism.
the depletion in the reaction time and product yields has been
started.
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