Amine-functionalized nano-NaY zeolite for the synthesis of N-acetyl pyrazoles and dihydropyrimidines

Article abstract of DOI:10.1002/aoc.6383

An efficient base-catalyzed synthesis of dihydropyrimidines and N-acetyl pyrazoles is reported using 1-(2-aminoethyl)piperazine-modified nano-NaY zeolite (ZeSi–AP) under mild and green conditions. The structure of the catalyst was identified by using FT-IR, XRD, TGA, DTA, DLS, SEM, TEM, and elemental analyses. This heterogeneous catalyst has many benefits, such as a simple work-up procedure, high product yield, and it is easily regenerated and reused at least for four cycles without losing its activity.

Full text of DOI:10.1002/aoc.6383

Received: 16 April 2021
DOI: 10.1002/aoc.6383
Revised: 14 June 2021
Accepted: 8 July 2021
R E S E A R C H A R T I C L E
Amine-functionalized nano-NaY zeolite for the synthesis of
N-acetyl pyrazoles and dihydropyrimidines
Raheleh Razavian Mofrad1
Ghasem Firouzzadeh Pasha2
| Hassan Kabirifard1
| Mahmood Tajbakhsh2
|
1Department of Chemistry, Islamic Azad
University, Tehran North Branch, Tehran,
Iran
2Department of Organic Chemistry,
Faculty of Chemistry, University of
Mazandaran, Babolsar, Iran
An efficient base-catalyzed synthesis of dihydropyrimidines and N-acetyl
pyrazoles is reported using 1-(2-aminoethyl)piperazine-modified nano-NaY
zeolite (ZeSi–AP) under mild and green conditions. The structure of the cata-
lyst was identified by using FT-IR, XRD, TGA, DTA, DLS, SEM, TEM, and ele-
mental analyses. This heterogeneous catalyst has many benefits, such as a
simple work-up procedure, high product yield, and it is easily regenerated and
reused at least for four cycles without losing its activity.
Correspondence
Mahmood Tajbakhsh, Department of
Organic Chemistry, Faculty of Chemistry,
University of Mazandaran, Babolsar
47416-95447, Iran.
K E Y W O R D S
Email: tajbaksh@umz.ac.ir
amine functionalized, dihydropyrimidines, green chemistry, N-acetyl pyrazoles, NaY
zeolite
Funding information
Islamic Azad University, Tehran North
Branch; University of Mazandaran
1 | INTRODUCTION
vital role in chemistry because of their pharmaceutical activ-
ities. DHPMs are considered as essential biological active
The application of solid catalysts in organic reactions is an
important issue to achieve green and efficient catalysts, as
they are widely used in environmentally friendly chemical
processes.[1] Recently, many homogeneous catalysts were
supported on the inorganic materials to overcome the dis-
advantage of homogeneous catalysts such as difficulty of
catalyst separation, using distillation and extraction proce-
dures, and reusability of catalyst.[2] One example of inor-
ganic supporting materials is nanozeolites due to their
thermal stability, availability, nontoxicity, nanosized and
large surface-to-volume ratio, and reusability.[3] Func-
tionalization of nanozeolites with organic molecules has
found many interests during last decades.[4] For example,
amine-functionalized nanozeolites have been used as cata-
lyst in organic transformations and also as efficient sor-
bents for capturing of gases such as CO2, H2S, and
methane from gas streams.[5]
compounds due to their activities as anti-inflammatory
agents,[7a] antihypertensive,[7b] anti-HIV,[7c] antitumor,[7d]
calcium channel blockers,[7e] and antibacterial.[7f] In addi-
tion,
many
natural
compounds
containing
dihydropyrimidine moiety in their structures exhibit fasci-
nating pharmaceutical properties.[8]
The Biginelli reaction for the preparation of DHPMs
involves condensation of beta-keto esters, urea, and alde-
hydes in acidic media.[9a] The major disadvantage of this pro-
tocol is the substrate tolerance and low yields of products.[9b]
Several catalysts that reported for the synthesis of
DHPMs include InBr3,[10a] InCl3,[10b] LiClO4,[10c]
FeCl3Á6H2O,[10d]
NiCl2Á6H2O,[10e]
CuCl2,[10f]
LaCl3Á7H2O,[10g] bismuth triflate,[10h] BF3ÁEtoH/copper
(II) chloride,[10i] and boric acid.[10j]
Besides, five-membered heterocyclic rings possessing
two nitrogen atoms named as pyrazoles are known as
biological active molecules and important precursors for
the preparation of pyrazoline derivatives including
cyanopyridine, indoxacarb, carbohydrazide hydrazine,
N-Heterocyclic compounds including dihydropyrimi-
dines (DHPMs),[6a] pyrroles,[6b] imidazoles,[6c] benzimi-
dazoles,[6d] pyridines,[6e] pyrazines,[6f] and indoles[6f] have a
Appl Organomet Chem. 2021;e6383.
wileyonlinelibrary.com/journal/aoc
© 2021 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.6383

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RAZAVIAN MOFRAD ET AL.
pyrimidine, and N-acetylated pyrazolines.[11] These het-
erocycles display various pharmaceutical properties such
as treatment of Alzheimer's disease, anticancer, anti-
allergic, and anti-inflammatory activities.[12] Several
acidic and basic catalysts were reported to catalyze the
synthesis of N-acetylated 4, 5-dihydro-1H-pyrazoles.
These are included fly ash H2SO4,[11b] SiO2Cl,
triflouroacetic acid (TFA), methanesulfonic acid,
obtained from Merck company (Germany). NaY
nanozeolite (Si/Al = 2.5) was provided from Zeolyst cor-
poration (USA). The Electrothermal IA9100 (Essex, UK)
1
was used to measure melting points. H and 13C NMR
spectra were recorded by a Bruker Avance DRX-400 spec-
trometer (Bruker, Germany) using TMS as internal refer-
ence and in CDCl3 and DMSO-d6 as solvents. The
synthesized catalyst was characterized by TGA apparatus
(Netzsch, Selb, Germany), X-ray powder diffraction at
room temperature using Cu Kα source (Philips PW-
1830), FT-IR spectrometer (Bruker Tensor 27, Germany),
scanning electron microscopy (SEM) on MIRA 3- XMU
(Tescan, Brno, Czech Republic), dynamic light scattering
(DLS) on HORIBA SZ-100 (HORIBA, Ltd., Japan),
Brunauer–Emmett–Teller (BET) model, and t-plot
(BELsorp, Japan).
1,5,7-triazabicyclo[4.4.0]dec-5-ene
(TBD),
NaOH,
Cs2CO3, and K2CO3.[13] Bauer et al. have synthesized N-
acetylated pyrazolines in the presence of polymer bound
bases.[14] Although there are many reports for the prepa-
ration of N-acetylated 4,5-dihydro-1H-pyrazole deriva-
tives using various catalysts, the literature survey reveals
that there is no information available for the preparation
of these compounds in the presence of modified heteroge-
neous nanocatalysts. Although some of these methods
resulted in high yield of DHPMs and pyrazole derivatives,
many of these procedures suffer from disadvantages like
expensive catalysts, long reaction time, low yields, strong
acidic media, harsh reaction conditions, and difficult sep-
aration, recovery, and reusability of the catalyst. Hence,
affords to find milder and more efficient procedure to
synthesis DHPMs and pyrazole derivatives continued
to attract many interests.
2.2 | General procedure for the synthesis
of amine-modified nanozeolites with
1-(2-aminoethyl)piperazine (ZeSi–AP)
NaY nanozeolite (Ze, 1 g) was added to anhydrous tolu-
ene and refluxed for 30 min under nitrogen atmosphere.
Then, 3-cloropropyltrimethoxysilane (CPTMS, 1.82 ml,
10 mmol) was added into the above solution and refluxed
for 4 h. The mixture was then cooled to room tempera-
ture and filtered off to collect the solid. The solid was
extracted by a Soxhlet extractor using 150-ml ethanol
(99.5%) for 24 h to remove the unreacted CPTMS.
In this study, the synthesis of 1-(2-aminoethyl)
pipirazine-functionalized NaY zeolite and its application
as a heterogeneous catalyst in the preparation of
dihydropyrimidin-2(1H)-ones
and
N-acetylated
4,5-dihydro-1H-pyrazole derivatives in green solvents is
reported (Scheme 1).
After extraction, the solid was added to anhydrous
dichloromethane (30 ml) and stirred at room temperature
for 30 min under nitrogen. Then, 1-(2-aminoethyl) piper-
azine (AP) (1.31 ml, 10 mmol) and triethylamine
(1.38 ml, 10 mmol) were mixed with the above mixture
and stirred for 24 h at room temperature under inert
atmosphere. The mixture was filtered off to collect the
solid product ZeSi–AP, which then extracted by ethanol
2 | EXPERIMENTAL
2.1 | Methods and materials
3-Chloropropyl trimethoxysilane (CPTMS), 1-(2-amino
ethyl)pipirazine (AP), triethylamine, and solvents were
SCHEME 1 Synthesis of DHPMs and N-
acetylated 4, 5-dihydro-1H-pyrazoles using
functionalized NaY nanozeolite

RAZAVIAN MOFRAD ET AL.
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3
3
(99.5%, 150 ml) in a Soxhlet extractor for 24 h to remove
nongrafted amine. The solid product ZeSi–AP was dried
in an oven for overnight.
3.97 (q, 2H, J = 7.2 Hz, CH2), 5.09 (d, 1H, J = 2.8 Hz,
CH), 6.87 (d, 2H, 3J = 8.8, 2CHAr), 7.14 (d, 2H,
3J = 8.8 Hz, 2CHAr), 7.67 (s, 1H, NH), 9.15 (s, 1H, NH);
13C NMR (DMSO, 100 MHz): δ 165.8, 158.9, 152.6, 148.4,
137.5, 127.8, 114.1, 100.0, 59.6, 55.5, 53.7, 18.2, 14.5.
2.3 | General procedure to prepare
DHPMs 4a–n
2.5.3 | Ethyl 4-(3-hydroxyphenyl)-6-methyl-
2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (4c)
Aldehyde (2 mmol), ethyl acetoacetate (2 mmol), either
urea or thiourea (2.5 mmol), and ZeSi–AP (20 mg) in
EtOH (10 ml) were mixed and stirred at room tempera-
ture for an appropriate time (Table 5). The mixture was
filtered off and washed with ethanol to collect the cata-
lyst. The filtrate was evaporated under vacuum to give
the crude product, which then crystallized with ethanol
to obtain the pure DHPM product. 1H and 13C NMR spec-
tral data can be seen in Figures S1–S27.
White powder; 1H NMR (DMSO, 400 MHz): δ 1.10 (t, 3H,
3J = 7.2 Hz, CH3), 2.24 (s, 3H, CH3), 3.97 (q, 2H,
3J = 8.4 Hz, CH2), 5.42 (s, 1H, CH), 6.64–6.61 (m, 3H,
3
2CHAr + NH), 6.74 (d, 2H, J = 7.2, CHAr), 8.65 (s, 1H,
OH), 9.36 (s, 1H, NH); 13C NMR (DMSO, 100 MHz): δ
167.7, 158.0, 157.6, 150.6, 144.5, 129.5, 116.9, 114.3, 113.4,
101.0, 59.4, 52.9, 18.1, 14.5.
2.4 | General procedure to prepare N-
acetyl-substituted pyrazole derivatives 7a–n
2.5.4 | Ethyl 4-(2-hydroxyphenyl)-6-methyl-
2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (4d)
Chalcone 1 (2 mmol), acylhydrazine 2 (2.4 mmol), and
ZeSi–AP (25 mg) in EtOH (10 ml) were mixed and stirred
at 60ꢀC for an appropriate time (Table 8). Completion of
reaction was controlled by thin-layer chromatography
(TLC) using hexane/EtOAc (3:1) as eluent. The mixture
was filtered off and washed with ethanol to collect the
catalyst. The filtrate was evaporated under vacuum to
leave a solid residue, which then recrystallized from etha-
White powder; 1H NMR (DMSO, 400 MHz): δ 0.99 (t, 3H,
3J = 7.2 Hz, CH3), 2.23 (s, 3H, CH3), 3.89 (q, 2H,
3
3J = 8.4 Hz, CH2), 5.71 (s, 1H, CH), 7.02 (d, 2H, J = 8.0,
3
4
CHAr), 7.5–7.54 (td, 2H, J = 8.0, J = 1.6, 2CHA), 7.66
3
4
(dd, 2H, J = 8.0, J = 1.6, CHAr), 7.71 (s, 1H, NH), 9.33
(s, 1H, OH), 10.26 (s, 1H, NH); 13C NMR (DMSO,
100 MHz): δ 167.7, 158.0, 157.6, 150.6, 144.5, 129.5, 116.9,
114.3, 113.4, 101.0, 59.4, 52.9, 18.1, 14.5.
1
nol to produce pure products 7a–n. H and 13C NMR
spectral data can be seen in Figures S28–S57.
2.5 | Spectral data for selected products
2.5.5 | Ethyl 4-(4-chlorophenyl)-6-methyl-
2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (4e)
2.5.1 | Ethyl 4-(phenyl)-6-methyl-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4a)
White powder; 1H NMR (CDCl3, 400 MHz): δ 1.18 (t, 3H,
3J = 7.2 Hz, CH3), 2.36 (s, 3H, CH3), 4.09 (q, 2H,
3J = 7.2 Hz, CH2), 5.39 (s, 1H, CH), 5.91 (s, 1H, NH), 7.27
White powder; 1H NMR (CDCl3, 400 MHz): δ 1.18 (t, 3H,
3J = 6.8 Hz, CH3), 2.36 (s, 3H, CH3), 4.09 (q, 2H,
3J = 6.8 Hz, CH2), 5.41 (s, 1H, CH), 5.73 (s, 1H, NH),
7.29–7.34 (m, 5H, 5CHAr), 8.05 (s, 1H, NH); 13C NMR
(CDCl3, 100 MHz): δ 165.4, 153.2, 146.4, 142.1, 133.7,
128.8, 128.0, 101.1, 60.1, 55.1, 18.7, 14.1.
3
(d, 2H, 3J = 8.4 Hz, 2H, 2CHAr), 7.29 (d, 2H, J = 8.4 Hz,
2H, 2CHAr), 8.18 (s, 1H, NH); 13C NMR (CDCl3,
100 MHz): δ 165.6, 153.2, 146.2, 143.6, 128.7, 127.9, 126.4,
101.4, 60.0, 65.1, 55.8, 18.7, 14.1.
2.5.2 | Ethyl4-(4-methoxyphenyl)-6-methyl-
2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (4b)
2.5.6 | Ethyl 4-(2-chlorophenyl)-6-methyl-
2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (4f)
White powder; 1H NMR (DMSO, 400 MHz): δ 1.10 (t, 3H,
3J = 7.2 Hz, CH3), 2.24 (s, 3H, CH3), 3.72 (s, 3H, OCH3),
White powder; 1H NMR (DMSO, 400 MHz): δ 0.99 (t, 3H,
3J = 7.2 Hz, CH3), 2.30 (s, 3H, CH3), 3.89 (q, 2H,

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RAZAVIAN MOFRAD ET AL.
3J = 7.2 Hz, CH2), 5.42 (s, 1H, CH), 7.32–7.30 (m, 3H,
3CHAr), 7.40 (d, 1H, 3J = 7.6 Hz, CHAr), 7.70 (s, 1H, NH),
9.27 (s, 1H, NH); 13C NMR (DMSO, 100 MHz): δ 165.4,
157.7, 151.7, 149.7, 142.1, 132.1, 129.8, 128.2, 98.3, 57.7,
51.9, 18.1, 14.3.
3.75 (1H, dd, 2JHH = 17.6, 3JHH = 12.0 Hz, CH2), 3.79
(OCH3), 5.57 (1H, dd, 3JHH = 12.0, 3JHH = 4.8 Hz,
CH2), 6.86 (2H, d, 3JHH = 8.0 Hz, CHAr), 7.19 (2H, d,
3JHH = 8.0 Hz,
CHAr),
7.42–7.47
(3H,
m,
CHAr), 7.76–7.78 (2H, m, CHAr); 13C NMR
(100.6 MHz, CDCl3): δC 22.0, 42.3, 55.3, 59.4, 114.2,
126.6, 126.9, 128.7, 130.3, 131.4, 134.1, 153.9, 159.0,
168.9.
2.5.7 | Ethyl 4-(2,4-dichlorophenyl)-
6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (4g)
2.5.11 | 1-Acetyl-5-(4-bromophenyl)-
3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole
(7b)
White powder; 1H NMR (DMSO, 400 MHz): δ 1.00 (t, 3H,
3J = 7.2 Hz, CH3), 2.29 (s, 3H, CH3), 3.89 (q, 2H,
3J = 7.2 Hz, CH2), 5.59 (s, 1H, CH), 7.31 (d, 1H,
3J = 8.4 Hz, CHAr), 7.41 (dd, 1H, 3J = 8.4 Hz and
1
Light yellow powder; H NMR (400.1 MHz, CDCl3): δH
4J = 2.0 Hz, CHAr), 7.56 (d, 1H, J = 2.4 Hz, CHAr), 7.74
2.42 (CH3), 3.10 (1H, dd, 2JHH = 17.6, 3JHH = 4.8 Hz,
4
2
3
(s, 1H, NH), 9.30 (s, 1H, NH); 13C NMR (DMSO,
100 MHz): δ 165.2, 151.6, 150.0, 141.4, 133.1, 133.0, 129.1,
128.4, 97.9, 59.6, 51.6, 18.1, 14.3.
CH2), 3.73 (1H, dd, JHH = 17.6, JHH = 12.0 Hz, CH2),
3
3
3.86 (OCH3), 5.53 (1H, dd, JHH = 12.0, JHH = 4.8 Hz,
CH2), 6.95 (2H, d, 3JHH = 8.8 Hz, CHAr), 7.13 (2H, d,
3JHH = 8.4 Hz, CHAr), 7.44 (2H, d, 3JHH = 8.0 Hz,
CHAr), 7.69 (2H, d, 3JHH = 8.0 Hz, CHAr); 13C NMR
(100.6 MHz, CDCl3): δC 21.9, 42.2, 55.4, 59.3, 114.2,
121.4, 123.7, 127.4, 128.2, 131.9, 141.0, 153.6, 161.4,
168.7.
2.5.8 | Ethyl 4-(4-cyanophenyl)-6-methyl-
2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (4h)
White powder; 1H NMR (DMSO, 400 MHz): δ 1.08 (t, 3H,
3J = 7.2 Hz, CH3), 2.25 (s, 3H, CH3), 3.97 (q, 2H,
2.5.12 | 1-Acetyl-3,5-diphenyl-4,5-dihydro-
1H-pyrazole (7f)
3
3J = 7.2 Hz, CH2), 5.21 (d, 1H, J = 2.0 Hz, CH), 7.42 (d,
3
3
2H, J = 8.0, CHAr), 7.81 (d, 2H, J = 8.4 Hz, CHAr), 7.58
(s, 1H, NH), 9.31 (s, 1H, NH); 13C NMR (DMSO,
100 MHz): δ 165.5, 152.2, 150.4, 149.7, 133.0, 127.8, 119.2,
110.5, 98.7, 59.8, 51.6, 18.2, 14.5.
White powder; 1H NMR (400.1 MHz, CDCl3): δH 2.45
2
3
(CH3), 3.19 (1H, dd, JHH = 17.8, JHH = 4.4 Hz, CH2),
3.78 (1H, dd, 2JHH = 17.8, 3JHH = 12.0 Hz, CH2), 5.62
(1H, dd, 3JHH = 12.0, 3JHH = 4.4 Hz, CH2), 7.24–7.29
(3H, m, CHAr), 7.32–7.36 (2H, m, CHAr), 7.43–7.46
(3H, m, CHAr), 7.75–7.78 (2H, m, CHAr); 13C NMR
(100.6 MHz, CDCl3): δC 21.9, 42.4, 59.9, 125.5,
126.6, 127.6, 128.7, 128.9, 130.3, 131.4, 141.8, 153.8,
168.9.
2.5.9 | Ethyl 4-(4-nitrophenyl)-6-methyl-
2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (4i)
White powder; 1H NMR (CDCl3, 400 MHz): δ 1.21 (t, 3H,
3J = 6.8 Hz, CH3), 2.38 (s, 3H, CH3), 4.12 (q, 2H,
3J = 6.8 Hz, CH2), 5.54 (s, 1H, CH), 5.82 (s, 1H, NH), 7.54
(d, 2H, 3J = 7.6 Hz, 2H, 2CHAr), 7.67 (s, 1H, NH), 8.20 (d,
2H, 3J = 7.6 Hz, 2H, 2CHAr); 13C NMR (CDCl3,
100 MHz): δ 165.1, 150.3, 147.5, 144.6, 127.6, 123.9,
100.59, 96.6, 60.4, 55.1, 18.7, 14.2.
2.5.13 | 1-Acetyl-5-(4-methoxyphenyl)-
3-phenyl-4,5-dihydro-1H-pyrazole (7g)
White powder; 1H NMR (400.1 MHz, CDCl3): δH 2.43
2
3
(CH3), 3.17 (1H, dd, JHH = 17.8, JHH = 4.4 Hz, CH2),
3.75 (1H, dd, 2JHH = 17.8, 3JHH = 12.0 Hz, CH2), 3.79
3
3
(OCH3), 5.57 (1H, dd, JHH = 12.0, JHH = 4.4 Hz, CH2),
6.86 (2H, d, 3JHH = 8.4 Hz, CHAr), 7.19 (2H, d,
3JHH = 8.4 Hz, CHAr), 7.44–7.47 (3H, m, CHAr), 7.76–7.78
(2H, m, CHAr); 13C NMR (100.6 MHz, CDCl3): δC 22.0,
42.3, 55.3, 59.4, 114.2, 126.6, 126.9, 128.7, 130.3, 131.5,
134.1, 153.8, 159.0, 168.8.
2.5.10 | 1-Acetyl-3-(4-methoxyphenyl)-
5-phenyl-4,5-dihydro-1H-pyrazole (7a)
White powder; 1H NMR (400.1 MHz, CDCl3): δH 2.43
2
3
(CH3), 3.17 (1H, dd, JHH = 17.8, JHH = 4.8 Hz, CH2),

RAZAVIAN MOFRAD ET AL.
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2.5.14 | 1-Acetyl-5-(4-bromophenyl)-
3-phenyl-4,5-dihydro-1H-pyrazole (7j)
3.86 (1H, dd, 2JHH = 17.8, 3JHH = 12.0 Hz, CH2), 5.68
3
3
(1H, dd, JHH = 12.0, JHH = 4.0 Hz, CH2), 7.43 (2H, d,
3JHH = 8.4 Hz, CHAr), 7.44–7.49 (3H, m, CHAr), 7.75–7.77
(2H, m, CHAr), 7.75–7.77 (2H, m, CHAr), 8.21 (2H, d,
3JHH = 8.4 Hz, CHAr); 13C NMR (100.6 MHz, CDCl3): δC
21.8, 42.1, 59.4, 124.3, 126.6, 126.7, 128.8, 130.7, 130.8,
147.4, 148.8, 153.7, 169.1.
1
Cream powder; H NMR (400.1 MHz, CDCl3): δH 2.45
2
3
(CH3), 3.13 (1H, dd, JHH = 17.6, JHH = 5.2 Hz, CH2),
3.76 (1H, dd, 2JHH = 17.6, 3JHH = 12.0 Hz, CH2), 5.57
3
3
(1H, dd, JHH = 12.0, JHH = 5.2 Hz, CH2), 7.12 (2H, d,
3JHH = 8.4 Hz, CHAr), 7.44 (2H, d, JHH = 8.4 Hz, CHAr),
3
7.45–7.46 (3H, m, CHAr), 7.74–7.76 (2H, m, CHAr); 13C
NMR (100.6 MHz, CDCl3): δC 21.9, 42.2, 59.4, 125.6,
126.6, 127.4, 128.8, 128.9, 130.5, 132.0, 140.8, 153.9, 169.1.
2.5.18 | 1-Acetyl-5-(4-nitrophenyl)-3-phenyl-
4,5-dihydro-1H-pyrazole (7n)
1
Orange powder; H NMR (400.1 MHz, CDCl3): δH 2.46
2
3
2.5.15 | 1-Acetyl-5-(4-chlorophenyl)-
3-phenyl-4,5-dihydro-1H-pyrazole (7k)
(CH3), 3.17 (1H, dd, JHH = 17.6, JHH = 5.6 Hz, CH2),
3.86 (1H, dd, 2JHH = 17.6, 3JHH = 12.0 Hz, CH2), 5.68
3
3
(1H, dd, JHH = 12.0, JHH = 5.6 Hz, CH2), 7.43 (2H, d,
3JHH = 8.8 Hz, CHAr), 7.43–7.46 (1H, m, CHAr), 7.46–
7.47 (2H, m, CHAr), 7.75–7.77 (2H, m, CHAr), 7.75–7.77
1
Cream powder; H NMR (400.1 MHz, CDCl3): δH 2.44
2
3
(CH3), 3.14 (1H, dd, JHH = 17.8, JHH = 4.4 Hz, CH2),
3.76 (1H, dd, 2JHH = 17.8, 3JHH = 12.0 Hz, CH2), 5.57
(2H, m, CHAr), 8.21 (2H, d, JHH = 8.8 Hz, CHAr); 13C
3
3
3
(1H, dd, JHH = 12.0, JHH = 4.4 Hz, CH2), 7.19 (2H, d,
3JHH = 8.4 Hz, CHAr), 7.31 (2H, d, 3JHH = 8.4 Hz,
CHAr), 7.44–7.46 (3H, m, CHAr), 7.75–7.78 (2H, m,
CHAr); 13C NMR (100.6 MHz, CDCl3): δC 21.9, 42.2,
59.3, 125.6, 127.1, 128.8, 129.0, 130.4, 131.2, 133.4,
140.3, 153.7, 168.9.
NMR (100.6 MHz, CDCl3): δC 21.8, 42.0, 59.4, 124.2,
124.3, 126.6, 126.7, 128.6, 128.8, 128.9, 130.7, 148.8,
169.1.
2.5.19 | 4-(1-Acetyl-5-phenyl-4,5-dihydro-
1H-pyrazol-3-yl)benzonitrile (7o)
2.5.16 | 4-(1-Acetyl-3-phenyl-4,5-dihydro-
1H-pyrazol-5-yl)benzonitrile (7l)
White powder; 1H NMR (400.1 MHz, CDCl3): δH 2.45
2
3
(CH3), 3.15 (1H, dd, JHH = 17.6, JHH = 4.8 Hz, CH2),
3.82 (1H, dd, 2JHH = 17.6, 3JHH = 12.0 Hz, CH2), 5.62
White powder; 1H NMR (400.1 MHz, CDCl3): δH 2.45
(1H, dd, JHH = 12.0, JHH = 4.8 Hz, CH2), 7.37 (2H, d,
3JHH = 8.4 Hz, CHAr), 7.45–7.48 (3H, m, CHAr), 7.64 (2H,
3
3
2
3
(CH3), 3.14 (1H, dd, JHH = 17.8, JHH = 5.2 Hz, CH2),
3.83 (1H, dd, 2JHH = 17.8, 3JHH = 12.0 Hz, CH2), 6.63
d, JHH = 8.4 Hz, CHAr), 7.74–7.77 (2H, m, CHAr); 13C
3
3
3
(1H, dd, JHH = 12.0, JHH = 5.2 Hz, CH2), 7.36 (2H, d,
3JHH = 8.4 Hz, CHAr), 7.45–7.48 (3H, m, CHAr), 7.64 (2H,
NMR (100.6 MHz, CDCl3): δC 21.9, 42.1, 59.6, 111.6,
118.6, 126.5, 126.6, 128.8, 130.7, 130.8, 132.8, 146.9, 153.7,
169.0.
d, JHH = 8.4 Hz, CHAr), 7.74–7.77 (2H, m, CHAr); 13C
3
NMR (100.6 MHz, CDCl3): δC 21.9, 42.0, 59.6, 111.6,
118.5, 126.5, 126.6, 128.8, 130.7, 132.8, 146.8, 153.8, 169.1.
3 | RESULTS AND DISCUSSION
2.5.17 | 1-Acetyl-5-(4-nitrophenyl)-3-phenyl-
4,5-dihydro-1H-pyrazole (7m)
Amine-functionalized nanozeolite (ZeSi–AP) was synthe-
sized by reacting nanozeolite with CPTMS to generate
silane-functionalized nanozeolite (ZeSi), which then
treated with AP to afford the expected solid catalyst ZeSi–
AP as depicted in Scheme 2. The structure of the catalyst
1
Yellow powder; H NMR (400.1 MHz, CDCl3): δH 2.46
2
3
(CH3), 3.16 (1H, dd, JHH = 17.8, JHH = 4.0 Hz, CH2),
SCHEME 2 Synthesis of the catalyst
ZeSi–AP

6 of 15
RAZAVIAN MOFRAD ET AL.
was characterized by FT-IR, TGA, DTA, XRD, SEM, and
TEM techniques.
300ꢀC, which is related to the removal of the organic
chloropropyl groups. The TGA curve of ZeSi–AP repre-
sents two weight losses at <110ꢀC and at 200–400ꢀC,
which can be due to the removal of surface water and of
organic aliphatic amine groups, respectively.
According to the TGA data, the amount of loaded
amine onto the nanozeolite surface was calculated to be
around 1.43 mmol/g. Further, the results of CHN analy-
sis of ZeSi and ZeSi–AP shown in Table 1 reveal that the
higher percent of carbon atom and presence of nitrogen
atom in the structure of ZeSi–AP comparing with ZeSi
could certainly approve the successful immobilization of
AP on the nanozeolite. The amount of loaded AP was cal-
culated to be nearly 1.39 mmol/g from data in Table 1,
which is in good agreement with that obtained
from TGA.
Figure 1 shows the FT-IR spectra of Ze, ZeSi, AP, and
ZeSi–AP. The spectra of Ze, ZeSi, and ZeSi–AP exhibit
characteristic bands at 3300–3600, 1640, and 1095 cmÀ1
corresponding to O H stretching, O H bending, and
Si O stretching vibrations, respectively. Additional
absorption peaks at about 2957 cmÀ1 related to the C H
stretching vibrations of the methylene groups of propyl
chloride in the spectrum of ZeSi confirm the successful
attachment of the CPTMS group into the Ze surface. The
IR spectrum of AP shows the expected bands at
3486 cmÀ1 related to N H stretching vibrations of the
amine groups, 2800–2925 cmÀ1 associated with the C H
stretching, 1647 and 1458 cmÀ1 that are corresponding to
NH2 bending of the amine groups.[5a,b]
The IR spectrum of ZeSi–AP displays absorption
bands at 3565 cmÀ1 (N H stretching vibration), 1640
and 1458 cmÀ1 (NH2 bending vibrations), and 1100 cmÀ1
(Si O Si stretching vibration) confirming the successful
synthesis of aminoethyl piperazine functionalized
nanozeolite.
Thermogravimetric analysis (TGA) of the Ze, ZeSi,
and ZeSi–AP is depicted in Figure 2. The heating range
from 30ꢀC to 600ꢀC with a rate of 10ꢀC/min was applied
for all samples. As it can be seen in Figure 2 and DTA of
the samples (Figure 3), the thermogram of Ze displays a
weight loss at >200ꢀC, which is related to physically
absorbed surface water. The TGA profile of ZeSi shows a
weight loss at >150ꢀC that is attributed to the
physisorbed surface water and a weight loss at 275–
FIGURE 2 The TGA thermograms of Ze, ZeSi, and ZeSi–AP
FIGURE 3 The DTA thermograms of Ze, ZeSi, and ZeSi–AP
TABLE 1 The results of ZeSi and ZeSi–AP CHN analysis
Entry
Catalyst
ZeSi
C (wt %)
7.21
N (wt %)
—
1
2
ZeSi–AP
17.2
5.83
FIGURE 1 IR spectra of the Ze, ZeSi, AP, and ZeSi–AP

RAZAVIAN MOFRAD ET AL.
7 of 15
The morphology of the catalyst was characterized
by SEM and TEM images as demonstrated in Figures 4
and 5, respectively. As it can be seen in these figures,
the similarity of SEM and TEM images of Ze, ZeSi,
and ZeSi–AP indicates that the surface of NaY
nanozeolite has not been significantly changed during
the immobilization process. The mean particle sizes
were calculated to be ꢁ20–90 nm as specified in
Figures 4 and 5.
Moreover, elemental mapping of the ZeSi–AP
approves the presence of Al, Si, O, C, N, and O atoms in
the nanozeolite structure (Figure 6) and confirms that
FIGURE 4 SEM images of Ze, ZeSi, and ZeSi–AP
FIGURE 5 TEM images of Ze, ZeSi, and ZeSi–AP
FIGURE 6 Elemental mapping of the
ZeSi–AP, revealing the elemental
distributions of Al, Si, O, C, and N

8 of 15
RAZAVIAN MOFRAD ET AL.
the elements are uniformly distributed in the catalyst
surface.
Besides, the DLS analysis was performed to determine
the hydrodynamic diameter and particle size distribution
of ZeSi–AP (Figure 7). According to the DLS data, the
average particle size of the ZeSi–AP was found to be
64 nm with a narrow particle size distribution. The
results of DLS analysis are in good agreement with
the results of XRD and SEM analyses.
The crystal structure of Ze, ZeSi, and ZeSi–Ap were
studied by X-ray diffraction using a Cu Kα irradiation as
depicted in Figure 8. The diffraction pattern of the
annealed samples matched well with NaY zeolite struc-
ture (Reference Code 98-010-5558 Na2Al2Si5O13ÁxH2O).
In the range of the 2θ (10–50), nano-NaY zeolite
exhibited all the characteristic reflections: (311), (331),
(333), (440), (620), (533), (642), (733), (660), (555), (840),
(664), (931), and (666). The similarity of the XRD diffrac-
tion patterns of Ze, ZeSi, and ZeSi–AP certainly demon-
strates that the crystal structure of NaY nanozeolite
(Ze) has not been destroyed during functionalization
with CPTMS and AP, which is in good agreement with
the results of TEM and SEM analyses.[15]
FIGURE 7 The DLS results of the ZeSi–AP
Figure 9 exhibits the N2 adsorption–desorption iso-
therms of all samples, and data extracted from BET and
t-plot including total specific surface area (SBET), total
specific surface area (a1), external specific surface area
(a2), and micropore area (a1–a2) are tabulated in
Table 2. The isotherms of Ze, ZeSi, and ZeSi–AP were
type I, which is characteristic of the microporous
structures.[15b,c] It is clear from Table 2 that the specific
surface area, total specific surface area (a1), external
FIGURE 8 XRD patterns of Ze, ZeSi, and ZeSi–AP
FIGURE 9 BET and t-plot of Ze (a),
ZeSi (b), and ZeSi–AP (c)

RAZAVIAN MOFRAD ET AL.
9 of 15
specific surface area (a2), and micropore area (a1–a2)
are reduced from Ze to ZeSi and ZeSi–AP. These drastic
reductions in the surface area and pore volumes for
ZeSi and ZeSi–AP compared with Ze could be due to
attachment of organic molecules to the surface of the
zeolite, which could cause blockage and narrowing of
the zeolite pores and openings.[15d,e] Also, the amine
density on the surface of the ZeSi–AP was calculated to
be 2.36 amines/Å2 based on the CHN and BET
analyses.
The catalytic activity of the amine functionalized NaY
zeolite (ZeSi–AP) was studied in the reaction of aromatic
aldehyde 1, ethyl acetoacetate 2, and either urea or thio-
urea 3 in the presence of catalytic amount of the ZeSi–AP
to obtain DHPM derivative 4 (Scheme 3).
The reaction of benzaldehyde 1a (2 mmol), ethyl
acetoacetate 2 (2 mmol), and urea 3a (2.5 mmol) in the
presence of nanocatalyst in 10-ml ethanol was chosen as
a model reaction to achieve the optimal reaction condi-
tions. As it is clear in Table 3, the model reaction in the
TABLE 2 Data obtained from N2 adsorption–desorption isotherms
t-plot
BET
Total specific surface area
Catalyst (SBET, m2/g)
Total specific surface area
External specific surface area
(a2, m2/g)
Micropore area
(a1–a2, m2/g)
(a1, m2/g)
1147.0
211.3
Ze
872.36
248.9
3.54
3.07
1.54
0.38
1143.93
209.76
2.98
ZeSi
ZeSi–AP
3.36
SCHEME 3 Synthesis of DHPM derivatives
using ZeSi–AP
TABLE 3 Optimization of reaction conditions for the synthesis of DHPMs
Entry
Catalyst (mg)
Ze (10)
Solvent
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH:H2O
H2O
Temperature (ꢀC)
Time (min)
Yield %a,b
1
80
80
r.t
40
80
r.t
r.t
r.t
r.t
r.t
r.t
r.t
r.t
r.t
120
120
40
trace
trace
72
2
ZeSi (10)
3
ZeSi–AP (10)
ZeSi–AP (10)
ZeSi–AP (10)
ZeSi–AP (15)
ZeSi–AP (20)
ZeSi–AP (25)
ZeSi–AP (30)
ZeSi–AP (20)
ZeSi–AP (20)
ZeSi–AP (20)
ZeSi–AP (20)
ZeSi–AP (20)
4
40
74
5
40
74
6
40
79
7
40
92
8
40
92
9
40
92
10
11
12
13
14
90
65
120
60
47
MeOH
THF
68
60
63
Et2O
60
45
aReaction conditions: benzaldehyde (2 mmol), ethyl acetoacetate (2 mmol), and urea (2.5 mmol) in the presence of catalyst in 10-ml solvent.
bIsolated yields.

10 of 15
RAZAVIAN MOFRAD ET AL.
presence of Ze and ZeSi afforded only a trace amount of
the DHPM 4a in refluxing ethanol after 2 h, whereas in
the presence of ZeSi–AP, the reaction yield increased to
72% in ethanol at room temperature after 40 min indicat-
ing the role of the ZeSi–AP in this reaction (Entries 1–3).
Increasing temperature did not improve the product yield
TABLE 4 Comparison of the catalyst ZeSi–AP with those reported in the literature
Entry
Catalyst/amount
Conditions
Time (min)
Yield (%)
85[16a]
80[16b]
80[16c]
91[16d]
92[16e]
1
2
3
4
5
β-Cyclodextrine/0.5 mol%
Cellulose sulfuric acid/0.05 g
12-Molybdophosphoric acid/2 mol%
Silica sulfuric acid/0.23 g
Solvent-free/100ꢀC
CH3CN/100ꢀC
AcOH/reflux
EtOH/reflux
180
270
300
360
360
Silica gel-supported L-pyrrolidine-2-carboxylic acid-
4-hydrogen sulfate/212 mg
EtOH/reflux
6
Amberlyst-70/50 mg
H2O/90ꢀC
180
24 h
360
85
81[16f]
70[16g]
75[16h]
77[16i]
98[16j]
92a
7
Poly(4-vinylpyridine-co-divinylbenzene)–Cu(II)/20 wt%
12-Tungstophosphoric acid/2 mol%
Fe3O4@camphor/0.02 g
MeOH/reflux
AcOH/reflux
EtOH/r.t
8
9
10
11
CoFe2O4/TMU-17-NH2/20 mg
ZeSi–AP/20 mg
Solvent-free/80ꢀC
30
EtOH/r.t
40
aThis work.
TABLE 5 Synthesis of DHPM derivatives
Product
4a
Ar
X
O
O
O
O
O
O
O
O
O
O
S
Time (min)
Yield (%)a
TONb/TOF (h)c
Mp (ꢀC)
C6H5
40
30
30
45
60
10
60
30
30
30
40
40
60
40
60
92
92
88
85
90
87
95
94
90
85
86
82
80
83
86
66/100
66/132
63/126
61/81
65/65
62/391
68/68
68/135
65/129
61/122
62/94
59/89
56/56
60/91
62/62
207–210[16d]
200–202[16d]
162–165[16d]
198–201[16g]
213–215[16d]
213–216[16g]
250–251[16d]
176–179[16a]
207–208[16d]
223–225[16d]
207–209[16d]
220–222[16e]
180–182[16d]
181–183[16e]
236–238[16a]
4b
4-OMe C6H4
3-OH C6H4
2-OH C6H4
4-Cl C6H4
2-Cl C6H4
2,4-diCl C6H3
4-CN C6H4
4-NO2 C6H4
2-NO2 C6H4
C6H5
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
2-NO2 C6H4
3-OH C6H4
4-Cl C6H4
4-CN C6H4
S
4m
4n
4o
S
S
S
aIsolated yields.
bTON = moles of product formed/moles of loaded amine in the catalyst (based on CHN).
cTOF = TON per time (h).

RAZAVIAN MOFRAD ET AL.
11 of 15
(Entries 4 and 5). Increasing the catalyst loading to
15, 20, 25, and 30 mg gave a reaction yield of 92%, and
20 mg of catalyst loading was chosen as optimal value
(Entries 6–9). After optimization of catalyst loading, the
model reaction was screened in different solvents like
EtOH:H2O, H2O, EtOH, MeOH, THF, and Et2O (Entries
7 and 10–14), and the results in Table 3 indicate that eth-
anol is the best solvent for this reaction (Entry 7).
In order to demonstrate the merit of the present cata-
lytic method for the preparation of DHPMs, the model
reaction was compared with some of the catalysts previ-
ously reported in the literature (Table 4). It is clear from
this table that the model reaction with β-cyclodextrin and
CoFe2O4/TMU-17-NH2 as catalysts afforded 4a in 85%
and 98% yields under solvent-free conditions at 100ꢀC
and 80ꢀC after 3 h and 30 min, respectively (Entries
1 and 10). The other catalysts such as cellulose sulfuric
acid (Entry 2), 12-molybdophosphoric acid (Entry 3), sil-
ica sulfuric acid (Entry 4), silica gel-supported L-
pyrrolidine-2-carboxylic acid-4-hydrogen sulfate (Entry
5), amberlyst-70 (Entry 6), poly(4-vinylpyridine-co-
divinylbenzene)–Cu(II) complex (Entry 7), and
12-tungstophosphoric acid (Entry 8) afforded the product
(4a) in 70–92% yields at reflux temperature of the related
solvents after 3–24 h. Fe3O4@camphor gave 4a in 77%
yield at room temperature after 85 min (Entry 9). How-
ever, the introduced catalyst performed the model reac-
tion at room temperature and product (4a) was obtained
in 92% yield after 40 min (Entry 11).
To demonstrate the merit of this method, various
aldehydes 1 were treated with ethyl acetoacetate 2 and
urea or thiourea 3 under optimal conditions, and the
results were tabulated in Table 5. Both electron-donating
and electron-withdrawing substituents in the aromatic
ring of the benzaldehyde afforded reasonable yields of
the related products (Entries 1–14). All the synthesized
compounds have been already reported in the literature,
and their structures were confirmed by comparing their
1
physical and H and 13C NMR spectral data with those
reported in the literature.
A plausible mechanism is presented in Scheme 4 for
the formation of DHPMs 4. It appears that the initial
event involves the nucleophilic attack of urea 3a to alde-
hyde 1 to generate the intermediate 8, which then elimi-
nates one molecule of water to produce intermediate 9.
Then the Michael-type addition of enol 2 to intermediate
9
gives
10,
which
subsequently
undergoes
heterocyclization to provide the relevant product 4.[16]
The results of the above reaction to prepare DHPMs
encouraged us to investigate the catalytic activity of the
synthesized ZeSi–AP in the preparation of N-acetyl
pyrazole derivatives (Scheme 5). Treatment of chalcone
5f (2 mmol) with acyl hydrazine 6 (2.4 mmol) was
selected as a reference reaction and screened under dif-
ferent reaction conditions to achieve the highest yield of
the products 7a–n, and results are displayed in Table 6.
The model reaction in the presence of either Ze or ZeSi
(10 mg) at 80ꢀC generated only trace amount of the prod-
uct after 2 h, whereas in the presence of ZeSi–AP (10 mg)
gave 42% yield at room temperature after 1 h (Entries 1–
3). Increasing temperature to 40ꢀC, 50ꢀC, and 60ꢀC
increased the reaction yield to 64% after 1 h (Entries 4–
6), though higher temperature did not improve the yield
(Entry 7). The catalyst loading from 10 to 15, 20, 25, and
30 mg was investigated (Entries 8–11), and the optimum
amount of catalyst was determined to be 25 mg to
achieve the highest product yield (Entry 10). The model
SCHEME 4 The plausible mechanism for the preparation of
DHPMs
SCHEME 5 Synthesis of N-acetyl pyrazole
derivatives using ZS–AP

12 of 15
RAZAVIAN MOFRAD ET AL.
TABLE 6 Optimization of reaction conditions for the synthesis of N-acetyl pyrazoles
Entry
Catalyst (mg)
Ze (10)
Solvent
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH:H2O
H2O
Temperature (ꢀC)
Time (min)
Yield %a,b
1
80
80
r.t
40
50
60
80
60
60
60
60
60
60
60
120
120
60
60
60
60
60
60
60
60
60
60
60
60
trace
trace
42
2
ZeSi (10)
3
ZeSi–AP (10)
ZeSi–AP (10)
ZeSi–AP (10)
ZeSi–AP (10)
ZeSi–AP (10)
ZeSi–AP (15)
ZeSi–AP (20)
ZeSi–AP (25)
ZeSi–AP (30)
ZeSi–AP (25)
ZeSi–AP (25)
ZeSi–AP (25)
4
47
5
55
6
64
7
64
8
73
9
81
10
11
12
13
14
94
94
67
45
THF
52
aReaction conditions: chalcone (2 mmol), acylhydrazine (2.4 mmol), catalyst, and solvent (5 ml).
bIsolated yields.
TABLE 7 Comparison of the ZeSi–AP with other catalytic systems in the preparation of 7e
Entry
Catalyst/amount
Fly ash H2SO4/0.4 g
PS-DIEA/1 g
Conditions
Time (h)
Yield (%)
77[11b]
78[14]
74[13]
95[13]
80[13]
89[13]
90[13]
60[13]
94a
1
2
3
4
5
6
7
8
9
MW/solvent-free
EtOH/r.t
0.1
12
Sc(OTf)3/5 mol%
Methanesulfonic acid/1 equiv
SiO2Cl/30 mol%
TBD/0.1 equiv
MW/solvent-free/100ꢀC
4
EtOH/reflux
0.75
2
Solvent-free/120ꢀC
CH3CN/60ꢀC
24 h
5
KOH/1 equiv
EtOH/reflux
Pd(OAc)2–K2CO3/5 mol%
ZeSi–AP
1,4-Dioxane:water/100ꢀC
EtOH/60ꢀC
8 h
1
aThis work.
reaction in the presence of ZeSi–AP (25 mg) in different
solvents such as EtOH:H2O (1:1), H2O, and THF under
the same reaction conditions (60ꢀC, 1 h) led to lower
yield of the product 7e (Entries 12–14).
The advantages of ZeSi–AP in comparison with the
reported catalytic systems for the preparation of N-acetyl
pyrazoles were displayed in Table 7. As can be seen, the
amine-modified NaY nanozeolite promoted the model
reaction smoothly based on reaction time and yield.
According to Table 7 fly ash H2SO4 was employed as an
acidic catalyst under solvent-free conditions. This system
affords the N-acetyl pyrazoles in short time but in low
yield (Entry 1). In the case of polymer bound (N,N-
(diisopropyl)aminomethyl polystyrene [PS-DIEA]), a long
reaction time is required to obtain only low product yield
(Entry 2). Using other catalysts, such as Sc(OTf)3 (Entry
3), methanesulfonic acid (Entry 4), SiO2Cl (Entry 5),
1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) (Entry 6), KOH
(Entry 7), and palladium acetate (5 mol%) (together with
SPhos [10 mol%] and K2CO3 [2 M]) (Entry 8), results low
product yield in time-consuming reaction. It is clear that
the introduced catalytic system could be substantially
used under mild and green conditions to give high prod-
uct yield in short reaction time (Entry 9).
To extend the reaction scope, different chalcones
5b–o were treated with acyl hydrazine 6 to obtain
N-acetyl pyrazoles 7b–o. Table 8 shows that chalcones
with different substituents tolerate in this reaction and

RAZAVIAN MOFRAD ET AL.
13 of 15
TABLE 8 Preparation of N-acyl pyrazoles
Product
7a
Ar1
Ar2
Time (min)
Yield (%)a
TONb/TOF (h)c
48/48
Mp (ꢀC)
4-OMe C6H4
4-OMe C6H4
4-OMe C6H4
4-OH C6H4
2-OMe C6H4
C6H5
C6H5
60
60
60
75
75
60
75
90
75
60
60
50
50
60
60
84
88
85
81
82
94
79
77
84
87
85
93
94
86
83
133–135[17a]
7b
4-Br C6H4
4-Cl C6H4
C6H5
51/51
262–264
7c
49/49
172–174[17b]
212–214[17c]
128–130[17a]
119–121[11b]
74–76[17d]
210–213[17e]
108–110[11b]
118–120[17f]
107–109[11b]
115–117
7d
47/38
7e
C6H5
47/37
7f
C6H5
54/54
7g
C6H5
4-OMe C6H4
4-OH C6H4
4-Me C6H4
4-Br C6H4
4-Cl C6H4
4-CN C6H4
4-NO2 C6H4
C6H5
45/36
7h
7i
C6H5
44/29
C6H5
48/39
7j
C6H5
50/50
7k
7l
C6H5
49/49
C6H5
53/64
7m
7n
7o
C6H5
54/65
163–165[11b]
192–194[17g]
200–201
4-NO2 C6H4
4-CN C6H4
50/50
C6H5
48/48
aIsolated yields.
bTON = moles of product formed/moles of loaded amine in the catalyst (based on CHN).
cTOF = TON per time (h).
According to the literature review, a tentative mecha-
nism is depicted in Scheme 6. It is assumed that the
ZeSi–AP enhanced the nucleophilic attack of acyl hydra-
zine 6 to carbonyl carbon of chalcone 5 generating inter-
mediate 11, which then eliminates one molecule of water
to give intermediate 12. Intramolecular nucleophilic
attack of nitrogen atom of acyl hydrazine to beta carbon
of chalcone in 12 and subsequent dehydration leads to
five-membered pyrazole ring 7.[17a]
It is noteworthy to mention that in this catalytic
method, the catalyst is easily recovered and reused for
several runs. Figure 10 exhibits the recyclability of nano-
ZeSi–AP up to four cycles in the model reaction, which
certainly demonstrates the excellent catalytic perfor-
mance of the synthesized catalyst. The SEM image of
recycled ZeSi–AP after fourth consecutive cycles in
Figure 11 is similar to fresh catalyst (Figure 4) indicating
no significant change in the surface of the catalyst. To
explore the catalyst leaching, the reaction between benz-
aldehyde, ethyl acetoacetate, and urea was carried out
under optimized conditions. After 20 min (half of needed
time for completion of reaction), the reaction was
SCHEME 6 The suggested mechanism for preparation of N-
acetyl pyrazoles catalyzed by ZeSi–AP
high yield of corresponding products is obtained (Entries
1–14). All the synthesized N-acyl pyrazoles are known
and characterized with their melting point, 1H NMR, and
13C NMR spectra and comparison with data reported in
the literature.

14 of 15
RAZAVIAN MOFRAD ET AL.
catalyst in both reactions. It is suggested that this cata-
lytic system can be utilized for preparation of other
important heterocycles systems under mild and green
conditions.
ACKNOWLEDGMENTS
The authors are thankful to the University of
Mazandaran and Islamic Azad University, Tehran North
Branch, for partial support of this project.
CONFLICT OF INTERESTS
The authors declare that there is no conflict of interest.
FIGURE 10 Catalyst reusability in the model reaction
AUTHOR CONTRIBUTIONS
Raheleh Razavian Mofrad: Conceptualization; data
curation; formal analysis; investigation; methodology;
project administration; resources. Hassan Kabirifard:
Conceptualization; funding acquisition; project adminis-
tration; supervision. Mahmood Tajbakhsh: Conceptual-
ization; data curation; formal analysis; funding
acquisition; investigation; methodology; project adminis-
tration; resources; supervision; validation. Ghasem
Firouzzadeh Pasha: Conceptualization; data curation;
formal analysis; funding acquisition; investigation; meth-
odology; resources; software; supervision; validation;
visualization.
ORCID
Raheleh Razavian Mofrad https://orcid.org/0000-0002-
7536-5544
Hassan Kabirifard https://orcid.org/0000-0003-2680-
8051
FIGURE 11 SEM images of reused ZeSi–AP (after four cycles)
Mahmood Tajbakhsh https://orcid.org/0000-0002-4856-
1937
stopped and the catalyst was separated. The yield of prod-
uct was measured by GC (74%). The residue was then
allowed to react without catalyst for another 60 min.
After that, the reaction mixture was analyzed by GC, and
the result showed that no significant conversion was
observed after catalyst separation.
Ghasem Firouzzadeh Pasha https://orcid.org/0000-
0002-5054-2938
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In summary, 1-(2-aminoethyl)piperazine-modified nano-
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
How to cite this article: R. Razavian Mofrad,
H. Kabirifard, M. Tajbakhsh, G. Firouzzadeh
Pasha, Appl Organomet Chem 2021, e6383. https://
doi.org/10.1002/aoc.6383
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