Utilization of eggshell waste as green catalyst for application in the synthesis of 1,2,4,5-tetra-substituted imidazole derivatives

Article abstract of DOI:10.1007/s11164-018-03724-w

Abstract: Eggshell as a solid waste was loaded on a nano-Fe₃O₄ surface. Then, in one step, it (Fe₃O₄@eggshell) was converted to Fe₃O₄@Ca₃(PO₄)₂ as a nano-magnetic, green, cheap, and environmentally friendly catalyst. Techniques such as FT-IR, VSM, FESEM, TEM, EDX, XRD, and TGA were used to characterize the as-synthesized catalyst. The catalytic activity of Fe₃O₄@Ca₃(PO₄)₂ was evaluated in the synthesis of 1,2,4,5-tetra-substituted imidazole derivatives through a one-pot multicomponent reaction. The design of the experiment as a systematic statistical approach was used to obtain the optimum point of the reaction condition so that 0.05?g of the as-synthesized catalyst and 94.77?°C were the best condition (which provides 90% yield for the benchmark reaction). Then, 1,2,4,5-tetra-substituted imidazole derivatives in the optimum condition were synthesized with very low reaction times in good yields. The as-prepared catalyst was retrieved through a magnet and used several times without significant loss of catalytic activity. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s11164-018-03724-w

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-018-03724-w
Utilization of eggshell waste as green catalyst
for application in the synthesis of 1,2,4,5‑tetra‑substituted
imidazole derivatives
Maryam Mahmoudiani Gilan1 · Ardeshir Khazaei1 · Negin Sarmasti1
Received: 20 September 2018 / Accepted: 24 December 2018
© Springer Nature B.V. 2019
Abstract
Eggshell as a solid waste was loaded on a nano-Fe3O4 surface. Then, in one step, it
(Fe3O4@eggshell) was converted to Fe3O4@Ca3(PO4)2 as a nano-magnetic, green,
cheap, and environmentally friendly catalyst. Techniques such as FT-IR, VSM,
FESEM, TEM, EDX, XRD, and TGA were used to characterize the as-synthesized
catalyst. The catalytic activity of Fe3O4@Ca3(PO4)2 was evaluated in the synthesis
of 1,2,4,5-tetra-substituted imidazole derivatives through a one-pot multicomponent
reaction. The design of the experiment as a systematic statistical approach was used
to obtain the optimum point of the reaction condition so that 0.05 g of the as-syn-
thesized catalyst and 94.77 °C were the best condition (which provides 90% yield
for the benchmark reaction). Then, 1,2,4,5-tetra-substituted imidazole derivatives
in the optimum condition were synthesized with very low reaction times in good
yields. The as-prepared catalyst was retrieved through a magnet and used several
times without signifcant loss of catalytic activity.
Graphical abstract
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-018-03724-w) contains supplementary material, which is available to authorized users.
*
Ardeshir Khazaei
Khazaei_1326@yahoo.com
1
Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
Vol.:(0123456789)
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M. Mahmoudiani Gilan et al.
Keywords One-pot reaction · Eggshell · Nano-magnetic
Introduction
Based on the number of species participating in the reaction, organic reactions can
be divided into three categories, namely, one-component reactions, two-component
reactions, and one-pot multicomponent reactions (MCRs) [1]. MCRs have attracted
keen interest from researchers due to advantages such as atom-economic, efective,
eco-friendly, high convergence, reduction of intermediate steps, reducing time and
energy, and a high bond-forming-index [2, 3]. Mannich 3CR [4], Strecker 3CR [5,
6], Passerini 3CR [7], Ugi 3CR [8], Pauson–Khand 3CR [9], an Leusen 3CR [10],
Gewald 3CR [11], Hantzsch 3CR [12], and Staudinger 3CR [13] are well-known
prototypical examples of MCRs. Synthesis of multi-substituted imidazoles is of
special importance due to their widespread biological activities [14]. Cimetidine
and losartan are among the examples which have entered the drug market. Synthe-
sis of 1,2,4,5-tetra-substituted imidazole (1245-TSI) derivatives through MCR is
important due to their biological properties [14]. With respect to the vital role of
catalysts in chemical reactions, a large number of catalysts and methods have been
used for the synthesis of 1245-TSI derivatives so that solid phase synthesis [15],
microwave irradiation [16], sodium benzenesulfnate [17], ZrCl4 [18], molecular
iodine [19], K5CoW12O40·3H2O [20], HClO4·SiO2 [21], Keggin-type heteropoly-
acid (HPA) [22], InCl3.3H2O [23], BF3·SiO2 [24], [(CH2)4SO3HMIM][HSO4] [25],
H6P2W18O62·24H2O [26], trifuoroacetic acid (TFA) [27], sulfated zirconia (SZ)
[28], silica-bonded propylpiperazine N-sulfamic acid [29, 30], SiO2-Pr-SO3H [31],
and Fe3O4@SiO2@TiO2 [32] have been used in the synthesis of 1245-TSI. However,
most of the cited catalysts are synthesized using pure chemicals. In recent years,
some environmental friendly and cheap materials such as eggshells have been used
in organic transformations. Calcinated eggshell has been used in biodiesel synthesis
[33], hydrogen/syngas, waste water treatment and high-value compounds [34]. In
addition, modifed eggshell, namely, eggshell/Fe3O4 [35], eggshell membrane/noble
metal nanoparticles [36], eggshell/Pd [37], Pd‐Ag/Al2O3 eggshell [38], eggshell/
Cu(OH)2 [39], Fe3O4@Ca(HSO4)2 [40] have been used in organic MCRs. However,
most of the cited catalysts are synthesized using pure and expensive chemicals with
multistep harsh reaction conditions. With this in mind, in the present work, egg-
shells as a waste product (high quantities of this solid residue are still being dis-
posed as waste in landflls without any pretreatment) were used for the synthesis
of nano-magnetic-Fe3O4@Ca3(PO4)2 as a green, cheap, environmentally friendly
catalyst, and its catalytic activity was evaluated in the synthesis of 1245-TSI deriva-
tives as added-value compounds. The results will provide an opportunity to moti-
vate researcher interest for further modifcation of eggshells to be utilized in organic
transformations.
1 3

Utilization of eggshell waste as green catalyst for application…
Experimental
Materials and apparatus
All chemicals were supplied from Merck and Fluka. The products were character-
1
ized using H,13C NMR, melting points as well as IR spectroscopy. The relevant
spectral data have been given in the Electronic supplementary information (ESI).†
1
The H, 13C NMR (250 MHz) was recorded on a Bruker Advance DPX-400 FT-
NMR spectrometer (δ in ppm). Melting points were measured using a Büchi
B-545 apparatus in open capillary tubes. Perkin Elmer PE-1600-FTIR was used
to record the infrared spectra of the products. To measure the mass reduction of
the catalyst, thermal gravimetric analysis (TGA) under a nitrogen atmosphere was
used. Field-emission scanning electron microscopy (FESEM), and transmission
electron microscopy (TEM) images were recorded with SIGMA VP-500 (ZEISS)
and Zeiss-EM10C-100 kV, respectively. Elemental analysis of the as-synthesized
catalyst was determined using an energy dispersive X-ray analysis (Oxford Instru-
ment). A vibrating sample magnetometer (VSM) model (MDKB) was used to
determine the saturation magnetization of the catalyst. To monitor the reaction
progress, thin layer chromatography (TLC; using silica gel SIL G/UV 254 plates)
was used.
Synthesis of the catalyst
Synthesis of Fe3O4 nanoparticles
The magnetic (Fe3O4) nanoparticles were synthesized by the coprecipitation method
[51]. First, 11.3 g FeCl3·6H2O and 5.6 g FeCl2·4H2O were dissolved in deionized
water at 80 °C and 600 rpm. After complete dissolution of the salts, 25 ml ammo-
nia (28 wt%) were added en masse to the solution. The resulting black solution was
vigorously stirred for 2 h at 80 °C in an N2 atmosphere. Then, the precipitated mag-
netic nanoparticles were separated from the solution using a magnet. Next, the solu-
tion was washed several times with water and then with acetone; fnally, 10 g stable
black magnetic dispersion was obtained and dried in an oven.
Preparation of eggshell powder
Eggshells were collected at home and washed with warm tap water, and then the
adhering membrane was separated manually. The eggshells were boiled in distilled
water for 2 h and then washed with distilled water. After drying in an oven (120 °C
for 2 h), their size was reduced using a cutting mill. Eggshells contain organic impu-
rities that should be removed before use so that 100 mL CH2Cl2 was added to the
powder which was subject to ultrasound for 2 h. Finally, the powder was separated
using fltration and dried in an oven.
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M. Mahmoudiani Gilan et al.
Preparation of Fe3O4@eggshell
An amount of 1 g of the eggshell powder was added to 100 mL of water and
stirred for 10 min at room temperature, and then 0.5 g as-synthesized nano-Fe3O4
was added to the mixture, which was dispersed for 15 min using ultrasound
and stirred for 2 h at 60 °C. There are two kind of intermolecular interactions
between Fe3O4 and CaCO3, which are electrostatic and electrodynamics, together
with electrostatic–electrodynamics, . The intermolecular interactions are strong
enough to prevent separation of the eggshell from the Fe3O4 which the experi-
mental results confrm. Finally, the nano-Fe3O4@eggshell (0.7 g) was fltered and
dried in an oven.
Preparation of Fe3O4@Ca3 (PO4)2
First, 0.7 g of Fe3O4@eggshell powder was dispersed in 50 mL acetone using
sonication, and then an extra amount of H3PO4 was added dropwise to the sus-
pension. The reaction medium was stirred continuously until all gases were
exhausted. In sequence, the acetone was evaporated at 60 °C up to LOD≈ 0 (loss
on drying). In this step, Fe3O4@eggshell was converted to Fe3O4@Ca3 (PO4)2
(1.1 g).
Results and discussion
Characterization of the catalyst
FT‑infrared
This technique is used to identify the functional group on the material/par-
ticles and the IR spectra of the Fe3O4, eggshell, Fe3O4@eggshell, Fe3O4@
Ca3(PO4)2, and Ca3(PO4)2 are shown in Fig. 1, in which is shown the IR spec-
trum of Fe3O4@eggshell as a hybrid of Fe3O4, and eggshell spectra confrm the
loading of eggshell on the Fe3O4 core. The CaCO3 is converted to Ca3 (PO4)2
[H3PO4 + CaCO3 → Ca3 (PO4)2 + H2O + CO2] in the synthesis procedure in which
H3PO4 is added to the Fe3O4@eggshell. Hence, the wave numbers which are
related to the CaCO3 must disappear and the wave numbers of Ca3 (PO4)2 must
appear in the IR spectra. To confrm the formation of Fe3O4@Ca3 (PO4)2, the IR
spectra of Ca3 (PO4)2 was recorded, which is shown in Fig. 1. As is clear, the IR
spectrum of Fe3O4@Ca3 (PO4)2 is matched with the IR spectrum of Ca3 (PO4)2.
Similarities are shown by dotted black rectangles. The IR spectra show the vibra-
3−
tion modes of PO4 ions at 467, 564, 602, 962, 1036, and 1102 cm−1. The wave
numbers of 636 and 3576 cm−1 are related to the hydroxyl groups [41].
1 3

Utilization of eggshell waste as green catalyst for application…
Fig. 1 FT-IR spectra of Fe3O4, eggshell, Fe3O4@eggshell, Fe3O4@Ca3(PO4)2, and Ca3(PO4)2
Vibrating sample magnetometer
This technique is used to investigate the magnetization property of a material.
The VSM of the as-synthesized Fe3O4 and the fnal catalyst, namely Fe3O4@
Ca3(PO4)2, are shown in Fig. 2. The degree of saturation magnetization of Fe3O4
decreases from 54 to 14.58 emu/g in the fnal catalyst (Fe3O4@Ca3(PO4)2).
Reduced saturation magnetization in Fe3O4@Ca3(PO4)2 is attributed to the nano-
magnetic layer (Ca3(PO4)2) in the core/shell structure of the as-synthesized cata-
lyst. Non-magnetic materials quench the surface moment, which in turn decreases
saturation magnetization. Although the saturation magnetization is reduced, the
Fig. 2 Magnetization curve of the nano-Fe3O4, and nano-Fe3O4@Ca3(PO4)2
1 3

M. Mahmoudiani Gilan et al.
Fig. 3 a SEM (left) and b TEM (right) images of the as-synthesized catlayst (Fe3O4@Ca3(PO4)2)
(a)
(b)
Fig. 4 a Normal distribution and b cumulative distribution functions of the normal distribution of the as-
synthesized catalyst (Fe3O4@Ca3(PO4)2)
as-synthesized catalyst can be easily separated from the reaction mixture and
used for the next cycles.
Field‑emission scanning electron microscopy and transmission electron
microscopy
These techniques are used to identify the size, shape, and morphology of the par-
ticles. The FESEM and TEM of the as-synthesized catalyst are shown in Fig. 3.
FESEAM (Fig. 3a) shows that the catalyst shape is spherical, but the SEM (Fig. 3b)
shows that Fe3O4 nano-particles are coated with a layer of Ca3(PO4)2 which is
obtained through the reaction of CaCO3 with H3PO4. In addition, the particle size
of the as-synthesized catalyst is shown in Fig. 4. Figure 4a shows the distribution of
particle size together with the well-ftted normal distribution function to these data.
1 3

Utilization of eggshell waste as green catalyst for application…
Mean and standard deviation of the particles size are 27 nm and 7 nm, respectively.
Figure 4b shows the experimental and ftted cumulative distribution functions of the
normal distribution, while Fig. 3 shows that 67%, and 90% of the particles size are
less than 30 nm and 40 nm, respectively.
Energy‑dispersive X‑ray spectroscopy (EDX)
This technique is used to determine the approximate contribution of each element of
the sample. The EDX pattern (elemental analysis) of the as-synthesized catalyst is
given in Fig. 5. The mass percent of the C, O, P, Ca, and Fe are 17.92, 45.71, 22.07,
560, and 8.70, respectively. The elemental analysis of the as-prepared catalyst con-
frms the formation of Fe3O4@Ca3(PO4)2 as the fnal catalyst.
X‑ray difraction (XRD)
This technique is used to identify size, purity, and crystalline nature of the particles.
The XRD patterns of Fe3O4, Fe3O4@eggshell, and Fe3O4@Ca3(PO4)2 are shown in
Fig. 6. XRD patterns together with Scherrer equation [D=(Kλ)/(βcosθ)] are used
to calculate the particle size of the as-synthesized catalyst. K, λ, β, and θ stand
for the dimensionless shape factor, X-ray wavelength, full width at half maximum
(FWHM) of the difraction peak, and Bragg difraction angle in radian, respectively.
It can be assumed that the nanoparticles have a spherical shape so the dimensionless
shape factor was set to 0.9. For the X-ray wavelength, copper K-Alpha (λ), namely
0.154184 nm, was used which is the averaged value of λKα1 =0.1540598 nm, and
λKα2 =0.154433 nm. The XRD pattern gives the values of β and θ. The values of 2θ,
FWHM, and the particle size of the as-synthesized catalyst are given in Table 1. The
averaged value of the nano-particle size based on the XRD technique is 9.73 nm,
which is inconsistent with the result of FESEM (27 nm). This diference can be
O Kα
4000
3500
P Kα
3000
FeLα
2500
2000
1500
1000
CaKα
CaKβ
FeKα
500
0
P Kβ
FeKβ
keV
15
0
5
10
Fig. 5 The elemental analysis of as-synthesized catalyst (Fe3O4@Ca3(PO4)2) using energy-dispersive
X-ray spectroscopy
1 3

M. Mahmoudiani Gilan et al.
Fig. 6 XRD pattern of nano-Fe3O4, nano-Fe3O4@eggshell, and nano-Fe3O4@Ca3(PO4)2
Table 1 X-ray difraction
(XRD) data for the as
synthesized catalyst (Fe3O4@
Ca3(PO4)2)
Entry 2θ
Peak width
(FWHM)
(radian)
Size (nm) Interplanar spacing
of the crystal (nm)
1
2
3
4
5
6
9.38
30.38 0.732
35.68 0.680
43.35 1.178
57.31 0.662
63.13 0.847
1.038
7.66
10.86
11.69
6.75
12.01
9.39
0.94
0.29
0.25
0.21
0.16
0.15
0.33
Mean
–
–
9.73
explained by the inability to measure smaller particles in the FESEM images, and
the K value in the Scherrer’s equation. The Bragg equation (dhkl =λ/2sinθ) was used
to calculate the distance between the layer (d-spacing or interplaner spacing) in the
crystalline structure of as-synthesized catalyst, and the results are given in Table 1.
Thermal gravimetric analysis and diferential thermal analysis (DTA)
Thermal stability of catalyst is a key factor which infuences the catalytic activity,
and the TGA of the as-prepared catalyst is shown in Fig. 7. The frst mass loss up to
105 °C is attributed to the release of adsorbed water. The second loss, from 105 up
to 510 °C, can be attributed to the residue of the eggshell organic matters. The mass
loss above 510 °C might be related to the loss of CO2 from the unreacted CaCO3. In
addition, diferential thermal analysis (DTA) (Fig. 7) confrms the steps of the as-
synthesized catalyst weight loss. Figure 7 shows that the as-synthesized catalyst is
stable and can be used in high-temperature organic reactions.
1 3

Utilization of eggshell waste as green catalyst for application…
Fig. 7 Thermal gravimetric analysis and diferential thermal analysis of the as-synthesized catalyst
Fe3O4@Ca3(PO4)2
BET and BJH analysis
The BET and BJH techniques are used to characterize the surface and pores of a
solid material. Accordingly, the surface area, cavity volume and cavity diameter
are 1.355 × 105 cm2/g, 0.02 cm3/g and 2.26 nm, respectively, for the as-synthe-
sized catalyst.
Evaluation of the catalytic activity of nano‑Fe3O4@Ca3(PO4)2
Efect of solvent type on the reaction
Solvents play an important role in chemical reactivity so that the rate of a reac-
tion may change by orders of magnitude when the solvent is changed. The sol-
vent efects are explained by the interaction of a solvent with the reactants and
the transition state of the reaction [42]. Considering this issue, the kinetic efect
of diferent solvents, namely ethyl acetate (EtOAc), acetonitrile (CH3CN), water,
n-hexane, and ethanol (EtOH), were investigated. Using these solvents, the time
and reaction yields of the benchmark reactions are given in Table 2. The kinetic
efect of the solvents can be explained by the dipole moment of the solvents,
which are given in Table 2. By increasing the dipole moment, the reaction yield
decreases, which can be attributed to the change of the Gibbs free energy of the
reactant and the transition state. On the other hand, the reaction was carried out
in a solvent-free condition so that the maximum yield was achieved in a short
time. A reduced reaction yield in a solvent is related to the cage efect of the sol-
vent [43], which reduces the mobility of the reactant, which in turn hinders react-
ing solutes from getting to each other in a solution.
1 3

M. Mahmoudiani Gilan et al.
Table 2 Efect of solvent type
and solvent-free condition on
the reaction yield
Entry
Solvent
Time (min)
Yielda (%)
Dipole
moment
(Debye)
5
6
2
4
3
n-Hexane
EtOH
EtOAc
H2O
70
80
75
>100
>100
35
30
25
–
0
1.69
1.78
1.85
3.3
CH3CN
–
aIsolated yield
Optimization of reaction conditions
Optimization of the reaction operating conditions from the reaction time and yield
point of view is highly important in organic synthesis. The conventional method
is a one-factor-at-a-time which is currently used by many chemists. This method
sufers from the disadvantages of a large number of experiments and a failure
to fnd the correct optimal point [44–46]. To overcome these shortcomings, the
design of experiment (DOE) has been developed and is used as a multivariate
statistical approach. Response surface methods (RSM) are the most efcient and
well-known DOE approach used by researchers. Among the RSM methods, the
central composite design (CCD) and Box–Behnken design (BBD) are the two
reliable methods [47]. In this work, the CCD method was used to design the
required experimental points which must be carried out in the laboratory.
Briefy, amounts of the as-synthesized catalyst and temperature were used as
the two main factors afecting the reaction yield at a specifed time. From now on,
the amount of catalyst, temperature, and reaction yield are shown with X1, X2, and
Y. The experimental points which must be carried out are given in Table 3. X1 and
X2 can be shown in a coded scale so that the maximum and minimum level of a
variable is shown by + 1, and − 1, respectively. The benchmark reaction (1 mmol
benzaldehyde derivtives + 1 mmol aniline + 1 mmol benzyl, and 1.2 mmol ammo-
nium acetate) was carried out in the conditions given in Table 3 and ceased after
15 min. The product was purifed through crystallization at room temperature.
The crystallization yield of the reactions is given in Table 3.
Optimum reaction condition
To fnd the optimum reaction condition, it is necessary to establish a relationship
between the independent (X) and dependent variables (Y). From a mathematical
point of view, this can be achieved through Talyor expansion as follows:
Y = ꢀ0 + ꢀ1X1 + ꢀ2X2 + ꢀ12X1X2 + ꢀ11X12 + ꢀ22X22 + ꢁ
(1)
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Utilization of eggshell waste as green catalyst for application…
Table 3 The designed experimental points by the BBD method, and the obtained benchmark reaction
yields
Runs
Efective variable
Response
X1 (amount of catalyst)
X2 (temperature)
Coded levels
Actual levels
Coded levels
Actual levels
Yield
1
2
3
4
5
6
7
8
0
0
−1
−1
1
1
0
0
−1
0
0.03
0.03
0.01
0.01
0.05
0.05
0.03
0.03
0.01
0.03
0.05
1
0
0
−1
1
0
−1
0
1
0
−1
110.00
70.00
70.00
30.00
110.00
70.00
30.00
70.00
110.00
70.00
30.00
46
44
43
33
48
47
35
45
40
44
37
9
10
11
1
where β, X, Y, and ε stand for coefcient, independent, dependent variable, and resi-
due of yield between experimental and the model, respectively. Equation (1) can be
shown in matrix notation as follows:
Y = ꢀX + ꢁ
(2)
The method of least squares approach can be used to fnd the best value of coef-
cients, as follows:
(
)
−1
ꢀ = XTX XTY
(3)
The fnal obtained equation, which relates the amount of the catalyst and the tem-
perature to the reaction yield, is as follows:
Y(yield) = 19.95 + 77.41X1 + 0.50X2 + 1.25X1X2 − 526.32X12 − 0.003X12
(4)
To show the reliability of the model [Eq. (4)], analysis of variance (ANOVA) was
carried out, as given in Table 4. The probability value (p value) of the model rejec-
tion is 0.0003, namely 3 in 3000, which shows that the model is reliable and signif-
cant from the statistical point of view. The p value of the X21 term is 0.7532, which
should be cancelled out from the model, but the model is signifcant and can be
used for further analysis. The coefcient of determination, denoted as R2, shows how
much the model is ftted to laboratory data. The value of 0.98 implies that the model
is well-ftted to the data. It should be noted that the high R2 values do not indicate
the ability of the model to predict the reaction yield in the new laboratory condi-
tions. To evaluate the predictive power of the model, an experimental data point in
Table 5 was removed and then the model was obtained from the 10 remaining data
points. Next, using the removed experimental data point, the yield was calculated
1 3

M. Mahmoudiani Gilan et al.
Table 4 Analysis of variance
(ANOVA) of the obtained
model for the yield versus
amount of catalyst and
temperature
Source
Probability
value (p
value)
Model (yield)
X1
X2
0.0003
0.0013
<0.0001
0.1042
0.7532
0.0007
0.9800
0.8374
0.1900
X1X2
X12
X22
R2
Predicted R2
Lack of ft
Table 5 Reaction time and yield
with and without catalyst in
optimum reaction conditions
Variables
Response
X1
X2
Time (min)
Yield (%)
With catalyst
Without catalyst
0.032
–
95
95
46
80
90
45
(a)
(b)
Fig. 8 R2 and predicted R2 of the reaction yield by the obtained model
from the obtained model and compared with the experimental reaction yield. This
procedure was looped over all the data points, and the Pred_R2 was calculated. In
fact, R2 and Pred_R2 show the correlative and predictive power of the model, respec-
tively, as shown in Fig. 8.
Figure 9 shows the 2-dimentional contours and 3-dimentional surface of the reac-
tion yield versus the amount of catalyst (X1), and temperature (X2). As is shown, the
reaction yield increases as the catalyst increases, but, with increasing temperature,
1 3

Utilization of eggshell waste as green catalyst for application…
Fig. 9 3-Dimensional surface (right) and the 2-dimentional contours (left) of the reaction yield versus
the amount of catalyst and temperature
the reaction yield frst increases and then decreases. The efciency has dropped
at high temperatures although the efect is not noticeable. This behavior can be
explained by the result of the TGA analysis.
To fnd the optimum reaction conditions using the constrained value of the
amount of catalyst (0.01≤X1 ≤0.05), and temperature (30≤X2 ≤110), the fmincon
algorithm in the MATLAB software was used so that 0.05 g and 94.77 °C were
obtained for the amount of the catalyst and temperature, respectively. The opti-
mum value of the reaction yield is 48.95 at the specifed reaction time (15 min). To
investigate the efect of the catalyst on the reaction time and yield, the benchmark
reaction was carried out in the optimum conditions with and without the catalyst,
and the results are given in Table 5. Using the catalyst, the reaction time and yield
are 46 min and 90%, respectively, while, without the catalyst, 45% yield has been
obtained in 80 min. These results show that the catalyst has a vital role in the reac-
tion progress.
Synthesis of 1,2,4,5‑tetra‑substituted imidazole derivatives at optimum reaction
condition
It is possible that the optimum reaction conditions for the synthesis of diferent deriva-
tives have slight diferences. However, the obtained optimum conditions for the bench-
mark reaction were used as generalized conditions in the synthesis of all the derivatives.
At the optimum reaction condition (100 °C, and 0.035 g catalyst), 1 mmol benzalde-
hyde derivatives+1 mmol aniline+1 mmol benzyl, and 1.2 mmol ammonium acetate
were stirred using a magnet. The reaction progress was monitored using TLC, so that,
after completion of the reaction, hot ethanol was added to the reaction media and the
catalyst was separated using a magnet. Finally, fne products were obtained through
crystallization in the ethanol. The synthesized products together with their melting
point, yield, and reaction time are given in Table 6. As is shown, benzene (including
electron-withdrawing and electron-donating functional groups) has been successfully
1 3

M. Mahmoudiani Gilan et al.
Table 6 Synthesized 1,2,4,5-tetra-substituted imidazole derivatives using the as-synthesized catalyst in
optimum reaction conditions
Product
1
2
3
4
5
6
m.p.a
Yield
Timeb
219–221
90
46
229–232
75
36
159–164
65
75
210–212
83
40
251–253.6
87
35
195–198.5
92
25
Product
7
8
9
10
11
m.p.a
Yield
Timeb
187–190
81
30
246–248.9
75
45
218–220.2
85
30
224–226.6
74
50
247.1–248.3
82
60
aMelting point
bTime (min)
used with high yield and short reaction times. One of the advantages of the as-prepared
catalyst is that the reaction times are very short (in the order of 25–75 min) compared
with those reported in the literature (in the order of hours) [23, 28, 31]. On the other
hand, phosphate-based catalysts such as potassium phosphate [48], Zr(KPO4)2 [49],
and mesoporous zirconium phosphate [50]2 have been reported, which confrm the util-
ity of the as-prepared catalyst.
Retrieval of the catalyst
In another study, the loss of catalyst activity in diferent cycles was investigated. After
separation of the as-synthesized catalyst using a magnet, the catalyst was washed with
ethanol and dried in an oven. The recycled catalyst used in the next cycle and the pro-
cedure was repeated for 4 cycles without any reduction in the reaction yield. To cancel
out the reaction time, all the cycles were stopped after 40 min. Then, the catalyst was
separated with a super-magnet. The resulting solution without any work-up was used
for crystallization of the product. The catalyst was dried in an oven for utilizeing in the
next cycle. Figure 10 shows the reaction yield versus the number of cycles.
1 3

Utilization of eggshell waste as green catalyst for application…
Fig. 10 Benchmark reaction
yield versus number of cycles
Conclusion
Based on the developed method, eggshells can be used as solid waste in the synthe-
sis of catalysts for use in organic synthesis. The short reaction time and good yields
show that the as-prepared catalyst (nano-Fe3O4@Ca3(PO4)2) has a good catalytic
activity in the one-pot synthesis of 1,2,4,5-tetra-substituted imidazole derivatives.
Thermal gravimetric analysis showed that the nano-Fe3O4@Ca3(PO4)2 has a good
thermal stability. The design of experiment was used as an efcient approach to fnd
the optimal reaction conditions, and 0.05 g of the catalyst and 94.77 °C were the
best conditions found in the current work. It is hoped that this work will motivate
researcher interest for further investigations in order to widen the possible conver-
sion of this waste into green and environment-friendly catalysts.
Acknowledgement The authors gratefully acknowledge partial support of this work by the Research
Afairs Ofce of Bu-Ali Sina University (Grant Number 32-1716 entitled development of chemical meth-
ods, reagents and molecules), Center of Excellence in Development of Chemical Method (CEDCM),
Hamedan, I. R. Iran.
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