Nanocrystalline Cu-ZnO as an green catalyst for one pot synthesis of 4, 4 -((phenyl)methylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) derivatives

Article abstract of DOI:10.1166/jnn.2019.16490

Synthesis of 4, 4′-((phenyl)methylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) derivatives was successively carried out using Cu doped ZnO nanomaterials. The nanocrystalline Cu-ZnO was obtained by decomposing as-synthesized copper-zinc oxalate intermediate

Full text of DOI:10.1166/jnn.2019.16490

Article
Journal of
Nanoscience and Nanotechnology
Vol. 19, 4623–4631, 2019
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Nanocrystalline Cu–ZnO as an Green Catalyst for One
Pot Synthesis of 4,4ꢀ-((phenyl)methylene)bis(3-methyl-
1-phenyl-1H-pyrazol-5-ol) Derivatives
Santosh Shinde1, Bhausaheb Karale1, Digambar Bankar5, Sudhir Arbuj5, Mansur Moulavi5,
Dinesh Amalnerkar3ꢀ∗, Taesung Kim3ꢀ4ꢀ∗, and Kaluram Kanade1ꢀ2ꢀ∗
1Post Graduate Department of Chemistry, Radhabai Kale Mahila Mahavidyalaya, Ahmednagar 414001, India
2Post Graduate Department of Chemistry, Yashwantrao Chavan Institute of Science, Satara 415001, India
3School of Mechanical Engineering, Sungkyunkwan University (SKKU) 300, Cheoncheon-dong, Jangan-gu,
Suwon, Gyeonggi, 440-746, South Korea
4SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon, 440-746, South Korea
5Centre for Materials for Electronic Technology (C-MET), Off Pashan Road, Panchwati, Pune 411008, India
Synthesis of 4,4ꢀ-((phenyl)methylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) derivatives was suc-
cessively carried out using Cu doped ZnO nanomaterials. The nanocrystalline Cu–ZnO was
obtained by decomposing as-synthesized copper–zinc oxalate intermediate at 520 ꢁC. The pre-
pared Cu–ZnO nanostructured catalyst was characterized with FTIR, X-ray diffraction, field emis-
IP: 5.62.159.99 On: Wed, 08 May 2019 03:05:48
sion scanning electron microscope and electron diffraction techniques. XRD analysis indicates the
Copyright: American Scientific Publishers
formation of highly crystalline hexagonal phase of ZnO along with the presence of monoclinic
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CuO. FESEM photographs shows the existence of plate like structures made up of small spheri-
cal shaped particles having size in the range of 30–50 nm. As-synthesized Cu–ZnO was used as
heterogeneous catalyst for one pot synthesis of 4,4ꢀ-((phenyl)methylene)bis(3-methyl-1-phenyl-1H-
pyrazol-5-ol) derivatives using phenyl hydrazine, ethyl acetoacetate and aromatic aldehydes. The
3-methyl-1-phenyl-1H-pyrazol-5-ol was obtained as in-situ precursor to the series of bis-pyrazolone
derivatives. The progress of reaction was monitored by thin layer chromatography. The obtained
1
organic product was further characterized and confirmed by FT-IR, H-NMR, 13C-NMR and HRMS
spectroscopic techniques. The Cu–ZnO catalyst confers upto 96% yield of pyrazolone derivatives
in ethanol solvent at refluxing condition. The Cu–ZnO catalyst was used successfully up to 5 cycles
without much loss of catalytic activity. Overall, the use of environmental friendly Cu–ZnO nano-
structures as a heterogeneous catalyst shows higher yield and lower reaction time towards the
synthesis of bispyrazolone derivatives by Tandem Knoevenagel/Michael reaction.
Keywords: Heterogeneous Catalyst, Nanocrystalline Cu–ZnO, Bispyrazolone, One Pot
Synthesis, Tandem Knoevenagel/Michael Reaction.
1. INTRODUCTION
such as antioxidant, antidepressant, gastric secretion stim-
ulatory, anti-inflammatory2 etc. Furthermore, these com-
pounds have been efficiently used as herbicidal, analgesic,
antimicrobial, antifungal and antipyretic drugs.3 These
compounds have unique electrical and optical properties4
too. The 4,4ꢀ-((aryl)methylene)bis(3-methyl-1-phenyl-1H-
pyrazol-5-ol) derivatives are routinely applied as pesti-
cides, fungicides, insecticides in the pesticide industries5ꢀ6
and used as chelating agent for the extraction of different
metal ions.7
The role of pyrazolone compounds has been increasing
day by day in pharmaceutical industries due to its nitro-
gen containing five membered heterocyclic moieties. Con-
sequently, nowadays the researchers are actively involved
in the synthesis of pyrazolone derivatives due to its enor-
mous applications as drug molecules.1 The pyrazolone
moiety containing compounds exhibits biological activities
∗Authors to whom correspondence should be addressed.
J. Nanosci. Nanotechnol. 2019, Vol. 19, No. 8
1533-4880/2019/19/4623/009
doi:10.1166/jnn.2019.16490
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Nanocrystalline Cu-ZnO as an Green Catalyst for bis-pyrazolyl and Allied Derivatives
Shinde et al.
In view of such intrinsic merits, the synthesis of
4,4ꢀ-((aryl)methylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol)
derivatives have been carried out using several homoge-
nous as well as heterogeneous catalysts such as 1,3,5-
tris(hydrogensulfato) benzene,8 lanthanum (III) triflate
on graphene oxide,9 LiOH,10 1-(carboxymethyl) pyri-
dinium chloride,11 NH4OAc,12 CsF,13 PEG-SO3H,14
Bronsted acidic ionic liquid supported on nanoporous
Na+-montmorillonite,15 Ce(SO4ꢁ2 · 4H2O, Fe(SO4ꢁ2 ·
(NH4ꢁ2 · 6(H2O),16 Cu-isatin schiff base complex,17
diammonium hydrogen phosphate,18 xanthan sulfuric
acid,19 3-aminopropylated silica gel,20 4-(succinimido)-1-
butane sulfonic acid,21 1,3-disulfonic acid imidazolium
tetrachloroaluminate,22 1-sulfopyridinium chloride23 and
2-hydroxy ethyl ammonium propionate.24 Present, the
homogenous catalysis in organic synthesis becomes an
environmental issue. Hence, the development of heteroge-
neous cost effective and easy to scale up method for the
synthesis of bispyrazolones has become an important area
of research.
2. EXPERIMENTAL DETAILS
2.1. Procedure for Synthesis of Cu–ZnO Catalyst
Zinc sulphate (99.9%, SD-fine), copper sulphate (99.9%,
SD-fine) and oxalic acid have been used as precursor mate-
rial. Oxalic acid (0.1 N) solution was added drop wise in
the mixture of zinc sulphate (0.1 N) and copper sulphate
(0.1 N) with constant stirring. The intermediate copper–
zinc oxalate was obtained and washed with distilled water
ꢁ
(1 lit). Obtained precipitate was dried at 100 C for 8 hrs.
The dried intermediate powder was decomposed at 520 ꢁC
to generate desired nanocrystalline Cu–ZnO.
2.2. Synthesis of 4,4ꢀ-((phenyl)methylene)bis(3-methyl-
1-phenyl-1H-pyrazol-5-ol) Derivatives Using
Cu–ZnO Catalyst
Phenyl hydrazine (1 mmol) and ethyl acetoacetate
(1 mmol) were taken in 10 ml ethanol in 25 ml single
neck round bottom flask equipped with condenser. Then,
nano Cu–ZnO catalyst was added in the reaction mixture.
Then reaction mass was refluxed for 60 min. The forma-
tion of intermediate pyrazolone was confirmed by TLC
technique. After completion of the reaction, different aro-
matic aldehydes (0.5 mmol) were added into above (same)
reaction mass for the next step. Then reaction mixture was
again refluxed for 30 min and completion of reaction was
checked by TLC. Reaction mixture was cooled and cata-
lyst was separated by centrifugation, washedꢁwith ethanol.
Nowadays, the synthesis of nano materials and their uti-
lization as an environmentally benign catalyst for organic
transformation25ꢀ26 as well as degradation of organic
waste27 is an important area of research. Numerous physi-
cal and chemical methods routinely used for the synthesis
of nanomaterial with unique morphology and uniform par-
ticle size.28 It has been established that nanosized materi-
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The used catalyst was oven dried at 120 C and recy-
cled for the same organic transformation. The filtrate was
concentrated to get solidified compound which was subse-
quently recrystallized in ethyl acetate. The obtained pure
Copyright: American Scientific Publishers
als exhibit altogether different or superior properties than
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those of large particle sized materials.29ꢀ30 Due to their
smaller size they have high surface to volume ratio that
increases the surface energy leading to distinctively differ-
ent chemical, electronic, optical, magnetic, and mechanical
properties.
1
products were characterized by H-NMR, 13C-NMR and
HR-MS techniques.
The enhancement of catalytic activity can be
accomplished by doping nanomaterials such as nano
n-propylsulphonated ꢂ-Fe2O3,31 nanosized Fe3O4 based
vanadic acid,32 Pd(0) NPs,33 sulfonated carbon/nano-
metal oxide composites34 and ZnO NPs35 for the
synthesis of 4,4ꢀ-((aryl)methylene)bis(3-methyl-1-phenyl-
1H-pyrazol-5-ol)s. Therefore, due to promising role and
high environmental stability of nanomaterials as a catalyst,
we have introduced Cu–ZnO nanocrystalline materials for
organic transformation.
In this context, herein, we report the synthesis of
nanocrystalline Cu–ZnO catalyst via solution based pre-
cipitation technique. The as-synthesized Cu–ZnO material
is used as an effective heterogeneous catalyst for the syn-
thesis of 4,4ꢀ-((aryl)methylene)bis(3-methyl-1-phenyl-1H-
pyrazol-5-ol)s in ethanol solvent at reflux conditions. We
observed that nanocrystalline Cu–ZnO catalyst produced
better yield for the Tandem Knoevenagel/Michael reaction.
The used catalyst is found environmental friendly and can
be recycled almost up to five times without further loss in
the product yield.
2.3. Characterization of Powder Catalyst and
Organic Compounds
Fourier Transform Infra-Red spectroscopy (FTIR) (IR
Affinity-1S) in the wavelength range of 400–4000 cm−1
was used to study the formation of nanocrystalline ZnO
and Cu–ZnO. Powder X-ray Diffractograms were recorded
on a Model Rigaku-D/MaX-2200V X-ray Diffractometer
(XRD) using CuKꢃ-radiation with Ni filter. The surface
morphology and particle size were determined using a
Field Emission Scanning Electron Microscope (FESEM
Model JEOL-JSM6700F). 1H and 13C-NMR were recorded
in DMSO-d6 solvent on Ascend 500 MHz Bruker NMR
spectrometer with tetramethylsilane (TMS) as internal ref-
erence. The HRMS data was taken in methanol solvent
using High Resolution Mass Spectrometer (HRMS, Bruker
Germany, Model Impact HD, UHR Impact II ESI-Q-TOF).
3. RESULTS AND DISCUSSION
The phase purity and morphology of prepared nanocrys-
talline Cu–ZnO catalyst was determined using following
techniques.
4624
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Shinde et al.
Nanocrystalline Cu-ZnO as an Green Catalyst for bis-pyrazolyl and Allied Derivatives
3.1. FTIR Patterns of As-Synthesized
ZnO and Cu–ZnO
Figure 1 shows the FT-IR pattern of as-synthesized
nanocrystalline ZnO and Cu–ZnO. The metal oxygen
stretching frequency of ZnO is confirmed by peak at
607.55 cm−1 (Fig. 1(a)). The Cu(II)–O bonds formation
peak appears at 601 and 508 cm−1 indicates the doping of
Cu in ZnO nanomaterials.36 The occurrence of sharp peaks
at 516.18 and 599.47 cm−1 in the spectrum of Cu–ZnO
nanoparticles (Fig. 1(b)) is the characteristic of Cu–ZnO
bond formation. The overall FTIR analysis is well matched
with the reported data which implies the presence of Cu
in ZnO matrix.
3.2. X-ray Diffraction Analysis
The XRD patterns of as-synthesized ZnO and Cu–ZnO
by solvent based precipitation technique are depicted in
Figure 2. The XRD pattern displayed in Figure 2(a) is well
matched with hexagonal phase of ZnO while, the XRD
pattern displayed in Figure 2(b) is well matched with the
monoclinic phase of CuO (tenorite) nano particles along
with hexagonal phase of ZnO. (In well concurrence with
the JCPDS Card no: 89-2531).
The crystallite size of pure ZnO and Cu–ZnO was cal-
culated using Scherrer’s equation.
Figure 2. XRD pattern of as-synthesized (a) ZnO and (b) Cu–ZnO.
The average particle size was found to be in the range
20–40 nm for ZnO and 15–35 nm for Cu–ZnO.
3.3. Morphological Study by FE-SEM
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Figure 3 shows the field emission scanning electron micro-
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scope photographs of typical ZnO (3a and 3b) as well as
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Cu–ZnO samples (3c and 3d).
The pure ZnO indicates the presence of thin sheets like
morphology having irregular shape composed of spongy
ZnO particles (Figs. 3(a and b)). With Cu-doping, the
appearance of irregular shaped flakes made up of evenly
distributed spherical ZnO particles is noticed (Figs. 3(c
and d)). Morphological study reveals the particle size
of this material is in the range 30–50 nm for both the
samples.
3.4. Energy-Dispersive X-ray Spectroscopy
(EDS) Analysis
Figure 4, exhibits the Energy-dispersive X-ray spec-
troscopy (EDS) analysis of as-synthesized Cu–ZnO. The
EDS analysis showed presence of Cu, Zn and O ele-
ments in the material. The EDS analysis illustrates nearby
35.11 wt.% Zinc, 26.50 wt.% Copper and 38.39 wt.%
Oxygen, elements present in the material. The percent dop-
ing (pre-chosen values) for the precipitation technique is
in close agreement with EDS report.
3.5. Synthesis of 4,4ꢀ-((phenyl)methylene)bis(3-
methyl-1-phenyl-1H-pyrazol-5-ol)
Derivatives
The different bispyrazolone derivatives were obtained as
per the procedure given in the experimental section. It has
Figure 1. FTIR of as-synthesized (a) ZnO and (b) Cu–ZnO
nanostructures.
J. Nanosci. Nanotechnol. 19, 4623–4631, 2019
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Nanocrystalline Cu-ZnO as an Green Catalyst for bis-pyrazolyl and Allied Derivatives
Shinde et al.
Figure 3. Field emission microscopes (FE-SEM) of ZnO (a and b) and Cu–ZnO (c and d).
The nanocrystalline Cu–ZnO makes carbonyl group of
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ethyl acetoacetate [A] more electron deficient and at the
Copyright: American Scientific Publishers
same time attack of lone pair of nitrogen form phenyl
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hydrazine [B] which creates more chances to remove
ethoxide group and to creates the co-ordinations with cat-
alysts. Further, it may be more possible to form the inter-
mediate in situ complex [C] which subsequently helps to
forms pyrazolone [D]. Then the intermediate pyrazolone
[D] undergoes knoevenagel type condensation with aro-
matic aldehyde [E] in presence of the catalyst to form
intermediate [F]. Simultaneously, the intermediate [D],
may react as second molecule pyrazolone with intermedi-
ate [F] in presence of the catalyst to convert into inter-
mediate [G]. Then intermediate [G] may get hydrolyzed
to yield 4,4ꢀ-((phenyl)methylene)bis(3-methyl-1-phenyl-
1H-pyrazol-5-ol) [H]. The proposed mechanism for
the synthesis of 4,4ꢀ-((phenyl)methylene)bis(3-methyl-1-
phenyl-1H-pyrazol-5-ol) by Tandem Knoevenagel/Michael
reaction by using Cu–ZnO nanosized catalyst is as shown
below.
Figure 4. EDS image of Cu–ZnO nanocomposite.
been observed, the catalytic reactivity of desired nanosized
ZnO and Cu doped ZnO as a heterogeneous catalyst for
the model reaction (Reaction scheme) was determined in
various solvents, different temperatures and by changing
mol percent of Cu–ZnO catalyst.
Reaction Scheme
O
O
HO
OH
NH–NH2
O
O
N
N
N
N
Nano Cu-ZnO
.Ethanol
+
H
Ar
N
OEt
N
Ar
5(a-j)
1
2
3
4(a-j)
4626
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Shinde et al.
Nanocrystalline Cu-ZnO as an Green Catalyst for bis-pyrazolyl and Allied Derivatives
NPs
NPs
=
Cu–ZnO
Ps
N
O
O
O
O
Cu–ZnO
Ethanol
N
N
N
N
H
OEt
..
..
H
[A]
O
[D]
H2N–HN
NPs
[C]
[B]
NPs
NPs
H
O
O
O
O
O
N
N
N
N
N
N
[D]
[E]
[F]
s
P
N
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Copyright: American Scientific Publishers
O
O
HO
OH
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H2O
N
N
N
N
H
N
N
N
N
H
Ar
Ar
[G]
[H]
Proposed mechanism for synthesis of 4,4ꢀ-
((phenyl)methylene)bis(3-methyl-1-phenyl-1H- pyrazol-5-
ol)s by using Cu–ZnO Nanocatalyst.
its polar protic behavior and also low dielectric constant.
Same reaction has been conceded out at different mmol of
catalyst (Table II, Entry 1 to 7). The increased mmol of
catalyst directly effects the yield of reaction. At the opti-
mized reaction conditions, recyclability study of catalyst
has been done for the synthesis stated in 5a (Fig. 5). The
catalyst was recycled up to 5 times and it was found that
recycled catalyst also confers the almost equal yield for
the same transformation.
Besides, the effect of electron donating or electron with-
drawing substitution on aromatic aldehyde at o/p position
has been studied for the synthesis of 5a–j at optimized
reaction conditions, using 0.25 mmol of Cu–ZnO cata-
lyst at refluxing condition in ethanol solvent (Table III,
Entry 1 to 10). Presence of electron donating OH (o/p)
group on aromatic aldehyde reduces the yield of reaction
(Table III, Entry 10). The halogenated aromatic aldehyde
compound (Table III, Entry 2, 3, 4 and 5) yielded bet-
ter than nitro aromatic aldehyde (Table III, Entry 7). The
One pot synthesis of Pyrazolone and its Tandem
Knoevenagel/Michael reaction with aromatic aldehyde has
been performed successively with different catalyst such as
ZnO and Cu–ZnO in various solvents at different temper-
ature (Table I, Entry 1 to 10). Generally, the synthesis of
homogenous pyrazolone derivative is more favored by acid
catalysis. Hence, in the present protocol, we have doped
Cu in ZnO to be used as heterogeneous catalyst. The dop-
ing of Cu in inorganic metal oxide is useful to increase
the surface acidity.38 Reported reaction is also favored to
acid catalyst which causes the enhancement in the yield
as compared to undoped ZnO (Table I, Entry 7 to 10).
We observed 94% yield (Table I, Entry 7) of compound
5a (as per the reaction scheme) in the ethanol solvent
with reflux condition as compared to the other solvents.
The increase of yield in ethanol solvent may be due to
J. Nanosci. Nanotechnol. 19, 4623–4631, 2019
4627

Nanocrystalline Cu-ZnO as an Green Catalyst for bis-pyrazolyl and Allied Derivatives
Shinde et al.
Table I. Optimization of reaction conditions for synthesis of 4,4ꢀ-
((phenyl)methylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol)s (5a).
Temperature
(ꢁC)
Time
(h)
Yield
(%)b
Entry
Catalysta
Solvent
1
2
3
4
5
6
7
8
9
10
ZnO NPs
ZnO NPs
ZnO NPs
ZnO NPs
ZnO NPs
Ethanol
Methanol
Water
Acetonitrile
Acetone
DMF
Ethanol
Ethanol
Ethanol
Ethanol
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
RT
2.0
2.0
2.0
2.0
2.0
2.0
1.5
4.0
2.5
2.0
76
65
55
57
62
52
94
48
62
81
ZnO NPs
Cu–ZnO NPs
Cu–ZnO NPs
Cu–ZnO NPs
Cu–ZnO NPs
45
55
Figure 5. Reusability study of Cu–ZnO for synthesis of 4,4ꢀ-
((phenyl)methylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) in ethanol
solvent at 1.5 hr.
Notes: aReaction condition: Phenyl hydrazine (1 mmol) 1, Ethyl Acetoac-
etate (1 mmol) 2, Benzaldehyde (0.5 mmol) 4a, Catalyst (1 mmol). bIsolated
yield.
128.13, 128.91, 129.65, 130.22, 140.21, 146.34; HRMS
m/z Calcd. For C27H24O2N4Cl [M + H]: 471.15, Found:
C27H24O2N4Cl [M +H]: 471.15.
benzaldehyde, 4 methyl benzaldehyde and 4 methoxy ben-
zaldehyde yielded the best value (Table III, Entry 1, 6
and 7) at optimized reaction condition.
3.6.3. 4,4ꢀ-((2-chlorophenyl)methylene)bis(3-methyl-
1-phenyl-1H-pyrazol-5-ol) (Table III,
Entry 3, 5c)
3.6. Spectral Data of As-Synthesized Compounds
3.6.1. 4,4ꢀ-((phenyl)methylene)bis(3-methyl-1-phenyl-
1H-pyrazol-5-ol) (Table III, Entry 1, 5a)
2.30 (s, 6H, CH3ꢁ, 5.14 (s, 1H, CH), 7.25 (m, J = 7.8 Hz,
3H), 7.30 (dt, J = 7.6 and 1.1 Hz, 1H), 7.40 (dd, J = 7.9
and 1.1, 1H), 7.44 (d, 7.8 Hz, 4H), 7.70 (d, 7.85 Hz, 4H),
7.82 (d, 7.0 Hz, 1H), 14.03 (bs, 2H); 13C NMR (75 MHz,
DMSO-d6) d ppm: 12.38, 32.07, 121.16, 126.12, 127.39,
128.51, 129.39, 129.92, 130.71, 132.29, 140.05, 146.37;
HRMS m/z Calcd. for C27H24O2N4Cl [M + H]: 471.15,
Found: C27H24O2N4Cl [M +H]: 471.1592.
1H NMR (500 MHz, DMSO-d6) d ppm: 2.31 (s, 6H,
CH3ꢁ, 4.92 (s, 1H, CH), 7.16 (m, 1H), 7.22 (m, 2H),
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7.28 (m, 4H), 7.43 (t, J = 8ꢄ0 Hz, 4H), 7.73 (d, J =
8ꢄ0 Hz, 4H), 14.42, (bs, 2H); 13C-NMR (75 MHz, DMSO-
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d6) d ppm: 12.27, 33.77, 120.86, 125.76, 126.25, 127.66,
128.55, 129.32, 129.53, 138.20, 143.23, 146.70; HRMS
m/z Calcd. for C27H24O2N4 [M + H]: 437.19 Found:
437.1985.
3.6.4. 4,4ꢀ-((4-fluorophenyl)methylene)bis(3-methyl-
1-phenyl-1H-pyrazol-5-ol) (Table III,
Entry 4, 5d)
3.6.2. 4,4ꢀ-((4-chlorophenyl)methylene)bis(3-methyl-
1-phenyl-1H-pyrazol-5-ol) (Table III,
Entry 2, 5b)
2.16 (s, 6H, CH3ꢁ, 4.63 (s, 1H, CH), 7.03 (m, 4H), 7.31
(t, J = 7.6 Hz, 4H), 7.36 (q, J = 8.5 Hz, 2H), 7.90 (d, J =
8.0 Hz, 4H), 13C NMR (75 MHz, DMSO-d6) d ppm:
13.42, 34.43, 102.68, 114.58, 114.75, 119.65, 123.58,
128.75, 129.39, 129.45, 146.23; HRMS m/z Calcd. for
C27H24O2N4F [M + H]: 455.15, Found: C27H24O2N4F
[M+H]: 455.1888.
2.174 (s, 6H, CH3ꢁ, 4.660 (s, 1H, CH), 7.07 (t, J =
7.8 Hz, 2H), 7.25 (d, J = 8.5 Hz, 2H), 7.32 (m, 6H),
7.88 (d, 7.8 Hz, 4H), 13.92 (bs, 2H); 13C NMR (75 MHz,
DMSO-d6) d ppm: 13.10, 34.19, 102.92, 119.96, 124.17,
Table II. Synthesis of 4,4ꢀ-((phenyl)methylene)bis(3-methyl-1-phenyl-
1H-pyrazol-5-ol) (5a) under different mol% of Cu–ZnO catalytic
condition.
3.6.5. 4,4ꢀ-((4-bromophenyl)methylene)bis(3-methyl-
1-phenyl-1H-pyrazol-5-ol) (Table III,
Entry 5, 5e)
2.16 (s, 6H, CH3ꢁ, 4.61 (s, 1H, CH), 7.05 (t, J = 8.0 Hz,
4H), 7.30 (q, J = 8.5 Hz, 4H), 7.38 (d, J = 8.5 Hz, 2H),
7.88 (d, J = 8.0 Hz, 4H), 13C NMR (75 MHz, DMSO-
d6) d ppm: 13.40, 34.59, 102.31, 118.48, 119.78, 123.68,
128.62, 128.76, 130.13, 130.95, 140.87, 146.34, 157.76;
HRMS m/z Calcd. for C27H24O2N4Br [M + H]: 517.10,
Found: C27H24O2N4Br [M +H]: 517.1067.
Entry
Catalysta (mmol)
Time (h)
Yield (5A)b
1
2
3
4
5
6
7
Nil
0.10
0.15
0.20
0.25
0.50
1.0
4.0
2.0
1.5
1.5
1.5
1.5
1.5
Trace
60
82
90
94
94
94
Notes: aReaction condition: Phenyl hydrazine (1 mmol) 1, Ethyl Acetoacetate
(1 mmol) 2, Benzaldehyde (0.5 mmol) 4, Catalyst. bIsolated yield.
4628
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Shinde et al.
Nanocrystalline Cu-ZnO as an Green Catalyst for bis-pyrazolyl and Allied Derivatives
3.6.6. 4,4ꢀ-((4-methylphenyl)methylene)bis(3-methyl-
1-phenyl-1H-pyrazol-5-ol) (Table III,
Table III. Contiuned.
Melting
Entry 6, 5f)
Entry
6
Compound (5a–j)
Time (min.) Yield point (ꢁC)
2.25 (s, 3H, CH3ꢁ, 3.31 (s, 6H, CH3ꢁ, 4.90 (s, 1H, CH),
7.07 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H),
7.24 (t, J = 7.5 Hz, 2H), 7.44 (t, 8.2 Hz, 4H), 7.71 (d,
8.0 Hz, 4H), 13.97 (bs, 2H); 13C NMR (75 MHz, DMSO-
d6) d ppm: 12.13, 21.00, 33.24, 120.95, 125.97, 127.54,
129.15, 129.38, 129.59, 135.26, 137.91, 139.72, 146.68;
HRMS m/z Calcd. for C28H27O2N4 [M + H]): 451.21,
Found: C28H27O3N4 [M+H]): 451.2139.
90
95
204
(203–204)6
OH HO
N
N
N
N
Me
5f
7
90
96
180
(181–183)7
Table III. Synthesis of (5a–j) using Cu–ZnO catalyst in ethanol solvent
HO
OH
N
N
at refluxing condition.
N
N
Melting
Entry
1
Compounda (5a–j)
Time (min.) Yieldb
90 94
point (ꢁC)
OMe
174
5g
(170–172)6
HO
OH
N
N
8
90
90
224
N
N
(224–226)6
HO
OH
N
N
N
N
5a
2
90
93
216
(215–217)6
NO2
OH HO
N
N
5h
N
N
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Copyright: American S9cientific Publishers
90
68
220
(217–218)37
HO
OH
Delivered by Ingenta
N
N
N
N
Cl
5b
NO2
3
90
90
234
(236–237)6
5i
HO
OH
N
N
10
90
85
150
(152–153)6
N
N
HO
OH
Cl
N
N
N
N
5c
4
90
90
180
(181–183)37
OH
HO
N
N
OH
5j
N
N
Notes: aReaction condition: Phenyl hydrazine (1 mmol) 1, Ethyl Acetoacetate
(1 mmol) 2, Aromatic aldehyde (0.5 mmol) 4(a–j), Catalyst (0.25 mmol). bIsolated
yield.
F
5d
3.6.7. 4,4ꢀ-((4-methoxyphenyl)methylene)bis(3-methyl-
1-phenyl-1H-pyrazol-5-ol)(Table III,
5
90
85
196
(198–200)7
HO
OH
N
N
Entry 7, 5g)
N
N
2.261 (s, 6H, CH3ꢁ, 3.907 (s, 3H, OCH3ꢁ, 4.789 (s,
1H, CH), 6.81 (d, J = 8.5 Hz 2H), 7.18 (m, 4H), 7.39
(t, J = 8.5 Hz, 4H), 7.77 (d, 7.6 Hz, 4H), 13.41 (bs,
2H); 13C NMR (75 MHz, DMSO-d6) d ppm: 12.37, 33.62,
55.44, 104.48, 113.82, 114.85, 118.80, 120.53, 125.09,
Br
5e
J. Nanosci. Nanotechnol. 19, 4623–4631, 2019
4629

Nanocrystalline Cu-ZnO as an Green Catalyst for bis-pyrazolyl and Allied Derivatives
Shinde et al.
128.64, 129.14, 136.20, 139.02, 146.56, 157.74; HRMS
m/z Calcd. for C28H26O3N4 [M + H]: 467.53 Found:
C28H27O3N4 [M+H]: 467.2093.
Acknowledgment: Santosh Shinde is indebted to
Council of Scientific and Industrial Research (CSIR),
Delhi for financial support to this work. He is also
thankful to the Principal of Radhabai Kale Mahila
Mahavidyalaya, Ahmednagar for providing necessary
facilities. Dr. Kaluram Kanade is very much thankful to
the management of Rayat Shikshan Sanstha, Satara for
supporting this research work.
3.6.8. 4,4ꢀ-((2-nitrophenyl)methylene)bis(3-methyl-
1-phenyl-1H-pyrazol-5-ol) (Table III,
Entry 8, 5h)
2.16 (s, 6H, CH3ꢁ, 5.32 (s, 1H, CH), 7.13 (t, J = 7.5 Hz
2H), 7.36 (t, J = 8.0 Hz, 4H), 7.39 (d, J = 8.2 Hz, 1H),
7.58 (t, J = 7.5 Hz, 1H), 7.64 (d, J = 7.5 Hz, 1H), 7.80
(d, J = 8.0 Hz, 4H), 7.87 (d, J = 8.0 Hz, 1H), 14.40
(s, 2H); 13C NMR (75 MHz, DMSO-d6) d ppm: 12.71,
29.98, 102.44, 120.24, 123.99, 124.64, 127.43, 129.00,
130.95, 131.99, 137.23, 139.64, 145.99, 149.84, 157.99;
HRMS m/z Calcd. for C27H24O4N5 [M + H]: 481.18,
Found: C27H24O4N5 [M+H]: 482.1836.
References and Notes
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IP: 5.62.159.99 On: Wed, 08 May 2019 03:05:48
HRMS m/z Calcd. for C27H24O4N5 [M + H]: 482.18,
Copyright: American Scientific Publishers
Delivered by1I2n. gSe. nBthaavanarushi, V. Kanakaiah, G. Bharath, A. Gangagnirao, and
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Entry 10, 5j)
1H NMR (500 MHz, DMSO-d6) d ppm: 2.208 (s, 6H,
CH3ꢁ, 5.09 (s, 1H, CH), 6.66 (t, J = 7.5 Hz 1H), 6.70
(d, J = 7.5 Hz, 1H), 6.91 (dt, J = 2 and 8.0 Hz, 1H),
7.11 (t, J = 7.5 Hz, 2H), 7.35 (t, J = 7.8 Hz, 4H), 7.69
(d, J = 2 and 7.5 Hz, 1H), 7.81 (d, J = 7.8 Hz, 4H),
12.96 (s, 1H), 13.62 (bs, 2H); 13C NMR (75 MHz, DMSO-
d6) d ppm: 12.68, 29.31, 102.42, 120.44, 123.70, 123.64,
125.43, 129.50, 130.25, 131.19, 136.23, 139.24, 145.19,
151.84, 157.99; HRMS m/z Calcd. for C27H24N4O3 [M+
H]: 452.18, Found: C27H24N4O3 [M+H]: 452.1836.
The spectral data of as-synthesized bispyrozolone
derivatives is well matched with reported compounds.
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4. CONCLUSION
One pot synthesis of bispyrozolone derivatives has been
performed using Cu–ZnO nanomaterial. It is found that,
our nanocrystalline Cu–ZnO sample worked as a green and
recyclable catalyst with enhanced yield of product within
short time. We speculate that nanocrystalline Cu–ZnO will
become an alternative and efficient catalyst for heteroge-
neous organic Tandem Knoevenagel/Michael reaction. The
as-synthesized catalyst is environment friendly.
4630
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Shinde et al.
Nanocrystalline Cu-ZnO as an Green Catalyst for bis-pyrazolyl and Allied Derivatives
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Received: 1 June 2018. Accepted: 30 July 2018.
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4631