Multicomponent synthesis of C-tethered bispyrazol-5-ols using CeO2 nanoparticles as an efficient and green catalyst

Article abstract of DOI:10.1007/s11164-015-2057-7

CeO₂ nanoparticles have been used as an efficient catalyst for the preparation of C-tethered bispyrazol-5-ols by pseudo five-component reaction of phenylhydrazine, acetylenedicarboxylates, and aromatic aldehydes at 70 °C in water. The use of no

Full text of DOI:10.1007/s11164-015-2057-7

Res Chem Intermed
DOI 10.1007/s11164-015-2057-7
Multicomponent synthesis of C-tethered bispyrazol-5-
ols using CeO nanoparticles as an efficient and green
catalyst
2
1
1
•
Javad Safaei-Ghomi
Bahareh Khojastehbakht-Koopaei
•
Mehrnoosh Asgari-Keirabadi
1
1
•
Hossein Shahbazi-Alavi
Received: 12 February 2015 / Accepted: 11 April 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract CeO nanoparticles have been used as an efficient catalyst for the prepa-
2
ration of C-tethered bispyrazol-5-ols by pseudo five-component reaction of phenylhy-
drazine, acetylenedicarboxylates, and aromatic aldehydes at 70 °C in water. The use of
no hazardous organic solvent, as well as atom economy, short reaction times, little
catalyst loading and high yields of products are some of the important features of this
protocol.
Graphical Abstract
&
Javad Safaei-Ghomi
safaei@kashanu.ac.ir
1
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, 51167 Kashan,
I. R. Iran
123

J. Safaei-Ghomi et al.
Keywords CeO nanoparticle Á Water Á C-tethered bispyrazol-5-ols Á
2
Multicomponent reaction
Introduction
The pyrazol ring system represents a common scaffold in numerous bioactive
compounds and has a number of pharmacological properties. The pyrazole
derivatives exhibit important biological properties, such as anti-malarial activity
[
1], fungicidal activity against wheat rust, phoma asparagi and antiviral activity
against TMV [2], antibacterial activity [3], inhibition of mycobacterium tuberculosis
4], anti-inflammatory and antioxidant activities [5], having the highest selectivity
[
for CB receptors [6], antiallergic activity [7] and antimicrobial activities [8].
1
Consequently, looking for efficient and simple methods for the synthesis of
pyrazoles is an interesting challenge that is at the forefront of organic chemistry. In
recent years, multicomponent reactions (MCRs) have been extensively utilized to
produce heterocyclic compounds with biological activity. These reactions provide
instantaneous access to complex compound libraries with diverse functionality [9–
1
3]. In addition, MCRs are environmentally friendly, and play a prominent role in
green chemistry [14, 15]. Therefore, the design of new MCRs with green procedures
has attracted great attention. Organic reactions carried out in water, without the use
of any hazardous and flammable organic solvents, are one of the current challenges,
especially in the areas of drug discovery, organic synthesis, and environmentally
benign synthesis [16]. The possibility of performing multicomponent reactions with
a green catalyst in water as a green solvent plays a prominent role in green
chemistry. In recent years, nano-catalysts have emerged as an alternative approach
for the improvement of many significant organic reactions [17–22]. Recently, many
of these catalysts have worked for millions of turnovers, at high reaction rates, and
with high selectivity. Therefore, there is a vital need to design new types of
sustainable heterogeneous catalysts for chemical synthesis. Among various
nanoparticles, cerium nanoparticles have received considerable attention because
of their unique properties and potential applications in diverse fields. CeO has
2
received much attention due to its many attractive characteristics, such as unique
UV absorption ability [23], ferromagnetism properties [24], depollution of noxious
compounds from gaseous streams originating from industrial productions and from
automobiles, as well as its being a major part of catalyst formulation for the
dehydrogenation of ethylbenzene to styrene [25] and a crucial addition to current a
series of three-way catalysts (TWCs) [26]. Recently, cerium and CeO nanoparticles
2
were used as an appropriate catalyst in many reactions, including synthesis of cyclic
ureas [27], polyhydroquinolines [28], 1,4-disubstituted-1,2,3-triazoles [29], direct
synthesis of imines from alcohol and amine [30], 1,3-diols [31], hydration of nitriles
to amides [32], and conversion of carbon dioxide into dimethyl carbonate with
2
-cyanopyridine [33]. The synthesis of C-tethered bispyrazol-5-ols has been
reported using MCR in the presence of acetic acid as catalyst and solvent [34]. This
method has certain drawbacks, including use of non-reusable catalyst and utilization
of specific conditions. Ideally, use of green solvent and utilizing environmental and
1
23

Multicomponent synthesis of C-tethered bispyrazol-5-ols…
green catalysts that can be simply recycled at the end of reactions are some of the
important features of each protocol. Herein, we wish to report a highly efficient
procedure for the preparation of C-tethered bispyrazol-5-ols using CeO nanopar-
2
ticles as an efficient catalyst at 70 °C in water (Scheme 1).
Experimental
Chemicals were purchased from the Sigma-Aldrich and Merck in high purity. All of
the materials were of commercial reagent grade and were used without further
purification. All melting points are uncorrected and were determined in capillary
1
13
tubes on a Boetius melting point microscope. H NMR and C NMR spectra were
obtained on a Bruker 400 MHz spectrometer with DMSO-d as solvent, using
6
tetramethylsilane (TMS) as an internal standard; the chemical shift values are in d.
Fourier transform infrared spectroscopy (FTIR) spectrum was recorded on Magna-
-
1
IR, spectrometer 550 Nicolet in KBr pellets in the range of 400–4000 cm . The
elemental analysis (C, H, N) was obtained from a Carlo ERBA Model EA 1108
analyzer. The N adsorption/desorption analysis (BET) was performed at -196 °C
2
using an automated gas adsorption analyzer (Tristar 3000, Micromeritics).
Powder X-ray diffraction (XRD) was carried out on a Philips diffractometer of
˚
X’pert Company with mono chromatized Cu Ka radiation (k = 1.5406 A).
Microscopic morphology of products was visualized by scanning electron
microscopy (SEM) (MIRA 3 TESCAN).
Preparation of CeO nanoparticles
2
Nano CeO was prepared according to the method reported in the literature, with
2
some modification [35]. CeO nanoparticles were prepared by a co-precipitation
2
procedure with post-annealing in air. Briefly, 3 g of highly pure Ce(NO ) Á6H O
3
3
2
was dissolved in a mixture of 50 ml deionized water and 20 ml alcohol. Afterward,
the appropriate amount of aqueous ammonia solution (28 wt%) was added to the
above solution until the pH value reached 8. Then the mixture was stirred for 4 h at
room temperature and then dried at 80 °C for 6 h. After, the solid was treated at
7
00 °C for 2 h to gain the CeO nanoparticles.
2
CO Me
2
Ar
CO Me
2
MeO C
Ar
2
NH2
CeO NPs
N
N
2
+
HN
2
+
2
O
N
Ar
N
CO Me
OH Ar
2
OH
Ar
1
2
3a-g
4
a-g
2
Scheme 1 Synthesis of C-tethered bispyrazol-5-ols using CeO nanoparticles
123

J. Safaei-Ghomi et al.
General procedure for the synthesis of C-tethered bispyrazol-5-ols
A mixture of acetylenedicarboxylate (2 mmol) phenylhydrazine (2 mmol) and
CeO nanoparticles (4 mol%, 14 mg) as catalyst were mixed in H O and then
2
2
stirred at room temperature for 5 min. Then the aromatic aldehyde (1 mmol) was
added into the mixture. The new mixture was stirred at 70 °C for an appropriate
time. Then it was allowed to cool to room temperature. The formed precipitate was
isolated by filtration. The product was dissolved in hot CH OH and the catalyst was
3
filtered. After cooling, the crude products were precipitated. The precipitate was
washed with EtOH to afford the pure product and then dried well under vacuum
pump.
Spectral data of products
Methyl 4-((3-(methoxycarbonyl)-5-hydroxy-1-phenyl-1H-pyrazol-4-yl)(4-nitro phe-
nyl)methyl)-5-hydroxy-1-phenyl-1H-pyrazole-3-carboxylate (4a) Golden powder,
-
1
mp 216–217 °C; IR (KBr) (vmax/cm ): 3433.44, 3072.26, 2954.06, 1731.84,
1
600.26, 1515.65, 1444.51, 1346.64, 1214.58, 1114.29, 841.23; H NMR
1
(
water of DMSO-d ), 6.91 (s, 1H, CH), 7.29–7.43 (t, J = 7.6 Hz, 6H, H-Ar), 7.51 (d,
400 MHz, DMSO-d ): d (ppm) 3.85 (s, 6H, 2OCH ), 4.81 (2OH exchanged with
6
3
6
J = 8 Hz, 2H, H-Ar), 7.79–7.85 (m, 4H, H-Ar), 8.14 (d, J = 7.6 Hz, 2H, H-Ar);
anal. calcd for C H N O : C, 61.16; H, 4.07; N, 12.30; Found: C, 61.12; H, 4.12;
N, 12.42.
2
9 23 5 8
Methyl 4-((3-(methoxycarbonyl)-5-hydroxy-1-phenyl-1H-pyrazol-4-yl)(4-chloro-
phenyl)methyl)-5-hydroxy-1-phenyl-1H-pyrazole-3-carboxylate (4b) White pow-
-
1
der, mp 226–228 °C; IR (KBr) (vmax/cm ): 3429.09, 3068.70, 2952.85, 1718.90,
1
1
599,42, 1492.71; HNMR (400 MHz, CDCl ): d (ppm) 3.91 (s, 6H, 2OCH ), 6.18
3
3
(
s, 1H, CH), 7.23 (m, 2H, H-Ar), 7.26 (m, 2H, H-Ar), 7.38 (m, 2H, H-Ar), 7.47 (m,
H, H-Ar),7.80 (m, 4H, H-Ar), 10.57 (2OH); anal. calcd for C H ClN O : C,
29 23 4 6
4
6
2.31; H, 4.15; N, 10.02; Found: C, 62.24; H, 4.19; N, 9.90.
Methyl 4-((3-(methoxycarbonyl)-5-hydroxy-1-phenyl-1H-pyrazol-4-yl)(2,4-dichlor-
ophenyl)methyl)-5-hydroxy-1-phenyl-1H-pyrazole-3-carboxylate (4c) White pow-
-
1
der, mp 207–209 °C; IR (KBr) (vmax/cm ): 3442.10, 2922.78, 1726.22, 1597.00,
1
1
499.92,1209.66,1110.18; HNMR (400 MHz, DMSO-d ): d (ppm) 3.77 (s, 6H,
6
2
OCH ), 4.69 (2OH exchanged with water of DMSO-d ), 6.72 (s, 1H,
1
3
6
3
CH),7.12–7.78 (m, 13H, H-Ar); CNMR (100 MHz, DMSO-d ): d (ppm) 31.13,
6
5
2.07, 105.23, 122.43, 122.63, 126.88, 127.02, 129.11, 129.27, 129.54, 131.56,
31.99, 133.88, 138.35, 157.26, 162.84; anal. calcd for C H Cl N O : C, 58.70;
1
H, 3.74; N, 9.44; Found: C, 58.65; H, 3.79; N, 9.51.
2
9
22
2 4 6
Methyl 4-((3-(methoxycarbonyl)-5-hydroxy-1-phenyl-1H-pyrazol-4-yl)(3-methyl-
phenyl)methyl)-5-hydroxy-1-phenyl-1H-pyrazole-3-carboxylate (4d) green pow-
-
1
der, mp 199–200 °C; IR (KBr) (vmax/cm ): 3429.92, 3027.60, 2951.71,
1
722.51,1600.24,1494.43, 1209.78, 1122.14, 863.29,761.80, 691.56; HNMR
1
1
23

Multicomponent synthesis of C-tethered bispyrazol-5-ols…
(
exchanged with water of DMSO-d ), 6.76 (s, 1H, CH), 6.93–7.76 (m, 14H, Ar-H);
400 MHz, DMSO-d ): d (ppm) 2.19 (s, 3H, CH ), 3.83 (s, 6H, 2OCH ), 4.83 (2OH
6
3
3
6
1
3
CNMR (100 MHz, DMSO-d ): d (ppm) 31.09, 31.97, 52.37, 107.99, 122.81,
6
1
1
6
23.36, 124.88, 126.96, 127.46, 128.31, 128.41, 129.37, 137.42, 137.53, 138.51,
42.65, 162.41. anal. calcd for C H N O : C, 66.91; H, 4.87; N, 10.40; Found: C,
3
0 26 4 6
6.99; H, 4.94; N, 10.32.
Methyl 4-((3-(methoxycarbonyl)-5-hydroxy-1-phenyl-1H-pyrazol-4-yl)(phenyl)-
methyl)-5-hydroxy-1-phenyl-1H-pyrazole-3-carboxylate (4e) brown powder, mp
-
1
2
87–289 °C; IR (KBr) (vmax/cm ): 3427.79, 2954.15, 1707.83, 1599.70, 1575.00,
1
7
59.86, 697.42; HNMR (400 MHz, DMSO-d ): d (ppm) 3.356 (s, 6H, 2OCH ),
6
3
3
.772 (2OH, exchanged with water of DMSO-d ), 6.695 (s, CH, 1H), 7.04–7.90 (m,
6
1
3
1
5H, Ar-H); C NMR (100 MHz, DMSO-d ): d (ppm): 32.23, 51.49, 105.37,
6
1
21.29, 125.30, 125.67, 128.01, 128.99, 130.54, 137.30, 139.77, 140.22, 158.50,
64.30. anal. calcd for C H N O : C, 66.41; H, 4.61; N, 10.68; Found: C, 66.48;
1
H, 4.72; N, 10.58.
2
9 24 4 6
Methyl 4-((3-(methoxycarbonyl)-5-hydroxy-1-phenyl-1H-pyrazol-4-yl)(2-chloro-
phenyl)methyl)-5-hydroxy-1-phenyl-1H-pyrazole-3-carboxylate (4f) white pow-
-
1
der, mp 267–269 °C; IR (KBr) (v /cm ): 3420.09, 2957.63, 1723.60, 1595.93,
max
1
1
552.37, 1207.75, 1131.41, 765.34; HNMR (400 MHz, DMSO-d ): d (ppm) 3.772
6
(
s, 6H, 2OCH ), 4.691 (2OH exchanged with water of DMSO-d ), 7.347 (s, 1H,
3 6
1
3
CH), 7.503 (m, 6H, Ar-H), 7.776 (m, 8H, Ar-H); CNMR (100 MHz, DMSO-d ): d
6
(
ppm): 31.15, 51.67, 102.04, 122.58, 122.81, 127.36, 127.85, 129.39, 129.55,
31.45, 131.92, 133.20, 138.77, 141.06, 151.96, 162.98. anal. calcd for C H
29 23-
1
ClN O : C, 62.31; H, 4.15; N, 10.02; Found: C, 62.24; H, 4.19, N, 10.09.
4
6
Methyl 4-((3-(methoxycarbonyl)-5-hydroxy-1-phenyl-1H-pyrazol-4-yl)(4-methylphe-
nyl)methyl)-5-hydroxy-1-phenyl-1H-pyrazole-3-carboxylate (4g) Green powder,
2
Fig. 1 XRD images of CeO NPs NPs
123

J. Safaei-Ghomi et al.
-
1
mp; 195–197 °C, IR (KBr) (vmax/cm ): 3432.33, 3063.23, 2952.85, 1729.77,
1
1
602.65, 1506.83, 1447.80, 1207.52, 1122.80; HNMR (400 MHz, DMSO-d ): d
6
(
DMSO-d ), 6.68 (s, 1H, CH), 6.76–7.77 (m, 14H, Ar-H), C NMR (100 MHz,
ppm) 2.196 (s, 3H, CH ), 3.760 (s, 6H, 2OCH ), 4.319 (2OH exchanged with water of
3 3
1
3
6
DMSO-d ): d (ppm): 29.3, 31.3, 51.68, 113.83, 122.81, 123.36, 124.88, 126.96,
6
127.46, 128.41, 129.37, 138.51, 142.65, 162.41. anal. calcd for C H N O : C, 66.91;
30 26 4 6
H, 4.87; N, 10.40; Found: C, 66.98; H, 4.96; N, 10.35
Results and discussion
The catalyst was prepared by the co-precipitation technique, with aqueous ammonia
solution as the precipitating agent. The XRD patterns for the CeO nanoparticle is
2
shown in Fig. 1. The pattern agrees well with the reported pattern for CeO2
nanoparticles (JCPDS No. 43-1002). The crystalline size was calculated from
FWHM using Scherrer’s formula and was observed to be 9–11 nm. The morphology
and particle size of CeO NPs was investigated by scanning electron microscopy
2
(SEM), as shown in Fig. 2. The SEM images prove particles with diameters that are
in the range of nanometers.
The choice of a suitable reaction medium is of vital importance for successful
synthesis. Initially, we had explored and optimized different reaction parameters for
the synthesis of C-tethered bispyrazol-5-ols by the pseudo five-component reaction
of phenylhydrazine (2 mmol), acetylenedicarboxylates (2 mmol) and 4-nitrroben-
zaldehyde (1 mmol) as a model reaction. As shown in Table 1, the solvent has a
great effect on the acceleration of the reactions. Several reactions were scrutinized
using various solvents, such as EtOH, CH CN, CHCl and water. The best results
3
3
were obtained at 70 °C in H O and the reaction gave satisfying results in the
2
presence of CeO nanoparticles (Table 1). The polarity, dipole moment,
2
2
Fig. 2 SEM images of CeO NPs NPs
1
23

Multicomponent synthesis of C-tethered bispyrazol-5-ols…
Table 1 Optimization of reaction conditions using different catalysts
2
Surface area (m /g)
a
Entry
Solvent
Catalyst (mol%)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
H
2
O
–
360
60
65
80
60
55
40
55
45
40
45
38
32
22
18
18
–
Nil
24
32
15
37
30
54
50
53
58
51
63
75
85
90
91
CH
3
CN
CuO (4)
NiO (3)
CuO (3)
2.2
2.1
0.9
11.6
1.2
4.9
1.9
3.2
–
EtOH
CHCl
EtOH
3
Al
CaO (4)
ZrO (5)
CuI (4)
Nd
CAN (2)
2
O
3
(5)
H
H
2
2
O
O
2
EtOH
EtOH
EtOH
EtOH
2
O
3
(4)
b
10
11
12
13
14
15
16
ZrO
2
(5)
4.9
5.2
33.2
33.2
33.2
33.2
H
2
O
CeO
CeO
CeO
2
2
2
(bulk)
EtOH
NPs (3)
NPs (2)
NPs (4)
NPs (6)
2
H O
H
2
O
CeO
2
H
2
O
CeO
2
Phenylhydrazine (2 mmol), acetylenedicarboxylates (2 mmol), and 4-nitrobenz-aldehyde (1 mmol)
Entry 15 is bold due to the best yield in 18 min for the reaction
a
Isolated yield
b
Cerium(IV) ammonium nitrate
Fig. 3 Effects of temperature variation on the yield and time of the model reaction
polarizability and hydrogen bonding of a solvent determine what type of compounds
it is able to dissolve. In this reaction, the use of polar solvents favors the reaction
mechanism. The catalyst showed best activity in water compared to other organic
solvents such as EtOH, CH CN, and CHCl . Water with a dielectric constant of
3
3
123

J. Safaei-Ghomi et al.
about 80 carried out reactions in good to excellent yields. Therefore, the use of polar
solvents with high dielectric constant favors the condensation reactions. Also, the
activity and stability of the CeO nanoparticles in water is maximal compared to
2
other solvents for the synthesis of C-tethered bispyrazol-5-ols. The significant
results presented in Table 1 are related to the hydrogen bonding between water or
ethanol and substrates that promote nucleophilic attack of the reactants.
When 2, 4, and 6 mol% of CeO nanoparticles were used, the yields were 85, 90,
2
and 90 % respectively. Therefore, performing the reaction with a higher catalyst
loading (6 mol%) had no significant effect on yield. The model reactions were
carried out in the presence of diverse catalysts, including NiO, CuO, Al O , CaO,
2
3
ZrO , CuI and CAN. When the reaction was carried out using CAN, CuI, ZrO NPs
2
2
and CeO NPs as the catalyst, the product could be obtained in a moderate to good
2
yield. To optimize the experiment temperature, the mixture was heated at different
temperatures (30, 40, 50, 60, 70, 80, 90 °C) (Fig. 3). The time of reaction was
decreased when the reaction temperature was raised from 50 to 70 °C. Therefore,
7
0 °C was chosen as the reaction temperature for all subsequent reactions.
With these hopeful results in hand, we turned to investigate the scope of the
reaction using various aromatic aldehydes as substrates under the optimized reaction
conditions (Table 2).
In the recycling procedure of CeO NPs, the product was dissolved in hot
2
CH OH and the catalyst was filtered. The solution was filtered and the
3
heterogeneous catalyst was recovered. The recovered CeO NPs was washed three
2
to four times with water and ethyl acetate, and dried at 100 °C for 5 h. We also
investigated recycling of the CeO NPs as catalyst for the synthesis of 4a. The results
showed that CeO NPs can be reused several times with a slightly decreased activity
2
2
(
run 1, 90 %; run 2, 89 %, run 3, 89 %; run 4, 88 %, run 5, 87 %). The catalyst
could be reused for five times with a minimal loss of activity. The activity of CeO2
NPs might be decreased by number of the regenerations. The morphology and
particle size of CeO nanoparticle was investigated by scanning electron micros-
2
copy (SEM) before use and after five times of reuse, with images shown in Fig. 4.
The SEM of CeO nanoparticles before and after the reaction showed identical
images. Interestingly, the morphology of the nanoparticles remained unchanged
2
Table 2 Synthesis of C-tethered bispyrazol-5-ols using CeO
2
NPs at 70 °C in water
a
Entry
Aldehyde (Ar)
Product
Time (min)
Yield (%)
mp (°C)
Lit. mp. (ref)
1
2
3
4
5
6
7
a
4-NO
4-Cl–C
2-4-Cl–C
3-Me–C
2
–C
6
H
4
4a
4b
4c
4d
4e
4f
18
18
22
25
20
22
24
90
88
86
83
85
85
83
216–217
226–228
207–209
199–200
287–289
267–269
195–197
– [34]
6
H
4
– [34]
6
H
3
–
–
–
–
–
6
H
4
6 5
C H
6 4
2-Cl–C H
6
4-Me–C H
4
4g
Isolated yield
1
23

Multicomponent synthesis of C-tethered bispyrazol-5-ols…
2
Fig. 4 SEM of CeO nanoparticles a before use, b after five times of reuse
before and after reaction. We believe that this is also a possible reason for the
extreme stability of the CeO nanoparticles presented herein.
2
The mechanism of these domino reactions is proposed in Scheme 2. The
chemistry of rare earth elements differs from main group and transition metals due
to the nature of the 4f orbitals, which are ‘buried’ inside the atom and are shielded
from the atom’s environment by the 4d and 5p electrons. The chemical nature and
the existing form of the catalyst play a vital importance for the reaction. These
characterization results clearly prove that ceria contains surface oxygen vacancy
sites as Lewis acidic sites. The surface population of vacancy sites depends on the
preparation method. During the reaction, water is adsorbed on these sites with only
medium strength and does not poison these sites, which explains why the ceria
catalyst is stable in water. We believe that the present findings will open a new vista
of ceria catalysts in aqueous reactions and greatly contribute to the understanding of
other oxides as heterogeneous catalysts [31]. The chemical nature and the existing
form of the catalyst play a vital importance for the reaction. From the results, it is
obvious that the CeO nanoparticle is the best catalyst among those examined and
2
reported in Table 1.
Theoretically, nanoscale heterogeneous catalysts should present higher surface
areas, which are chiefly responsible for their catalytic activity. We tested CeO bulk
2
2
2
with surface area 5.2 m /g and CeO NPs with surface area 33.2 m /g; yields were
2
63 and 90 %, respectively. So, the increased surface area owing to small particle
size improved reactivity.
An initial condensation of acetylenedicarboxylate and phenylhydrazine generated
,3-dipole intermediate, which sequentially underwent proton transfer and
1
aminolysis of the ester group, generating the pyrazolone derivative in situ. The
pyrazolone derivative was subjected with aromatic aldehydes, leading to arylidene
pyrazolones. In this mechanism, the surface atoms of CeO NPs activate the C=O
2
123

J. Safaei-Ghomi et al.
O
O
MeO C
2
O
O
H
N
+
CO Me
NH2
2
Ar'
NH2
NH CO Me
2
CO Me
2
HN
Ar'
HN
Ar'
OH
O
Ar
O
H
H
H CO
OH
N
Ar
O
3
MeO C
2
N
N
Ar'
N
N
MeO C
Ar'
2
Ar'
N
CO Me
H
2
H
O
Ar
MeO C
N
CO
Me
2
2
MeO C
MeO C
N
Ar'
2
2
Ar
O
N
N
N
N
N
N
OH OH
Ar'
Ar'
Ar'
=
CeO NPs
2
Scheme 2 Probable mechanism for the formation of C-tethered bispyrazol-5-ols using CeO
nanoparticles
2
group for better reaction with nucleophiles. These surface atoms behave as the
centers where chemical reactions could be catalytically stimulated. So the arylidene
pyrazolones were further reacted with pyrazolones generated in situ to give the final
C-tethered bispyrazol-5-ols derivatives.
Conclusion
In conclusion, we have developed a simple, green and highly efficient protocol for
the synthesis of C-tethered bispyrazol-5-ols using CeO nanoparticles as an efficient
2
catalyst at 70 °C in water. The procedure offers several advantages, including
cleaner reaction profiles and use of simply available reagents; it is cheap, has high
yields, a shorter reaction time and has easy experimental reusability of the catalyst
and little catalyst loading. This green nanocatalyst could be used for other
noteworthy organic reactions and transformations. Further investigations of similar
protocols are happening in our laboratory.
1
23

Multicomponent synthesis of C-tethered bispyrazol-5-ols…
Acknowledgments The authors acknowledge a reviewer who provided helpful insights. Meanwhile, the
authors are grateful to the University of Kashan for supporting this work through Grant No. 463562/XXII.
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