Synthesis of 4-((2-hydroxynaphthalen-1-yl)(aryl)methyl)-5-methyl-2-phenyl-1H-pyrazol-3(2H)-ones using nano-Zn-[2-boromophenyl-salicylaldimine-methylpyranopyrazole]Cl2 nanoparticles

Article abstract of DOI:10.1002/jccs.201800215

Nano-Zn-[2-boromophenyl-salicylaldimine-methylpyranopyrazole]Cl₂ (nano-[Zn-2BSMP]Cl₂) as a nanoparticle Schiff base complex and a catalyst was introduced for the solvent-free synthesis of 4-((2-hydroxynaphthalen-1-yl)(aryl)methyl)-5-

Full text of DOI:10.1002/jccs.201800215

Received: 5 June 2018
Revised: 1 November 2018
Accepted: 5 November 2018
DOI: 10.1002/jccs.201800215
A R T I C L E
Synthesis of 4-((2-hydroxynaphthalen-1-yl)(aryl)methyl)-
5-methyl-2-phenyl-1H-pyrazol-3(2H)-ones using nano-Zn-
[2-boromophenyl-salicylaldimine-methylpyranopyrazole]Cl2
nanoparticles
Hamid Goudarziafshar | Ahmad Reza Moosavi-Zare | Zahra Jalilian | Mehdi Abdolmaleki
Sayyed Jamaleddin Asadabadi University,
Nano-Zn-[2-boromophenyl-salicylaldimine-methylpyranopyrazole]Cl2 (nano-[Zn-
Asadabad, I. R. Iran
2BSMP]Cl2) as a nanoparticle Schiff base complex and a catalyst was introduced
Correspondence
Hamid Goudarziafshar, Sayyed Jamaleddin
for the solvent-free synthesis of 4-((2-hydroxynaphthalen-1-yl)(aryl)methyl)-
5-methyl-2-phenyl-1H-pyrazol-3(2H)-ones by the multicomponent condensation
reaction of various aromatic aldehydes, β-naphthol, ethyl acetoacetate, and phenyl
Asadabadi University, Asadabad 6541861841,
I. R. Iran.
Email: hamid_gafshar@yahoo.com
Ahmad Reza Moosavi-Zare, Sayyed Jamaleddin
Asadabadi University, Asadabad 6541861841,
I. R. Iran.
hydrazine at room temperature.
KEYWORDS
Email: moosavizare@yahoo.com
4-((2-hydroxynaphthalen-1-yl)(aryl)methyl)-5-methyl-2-phenyl-1H-pyrazol-3
(2H)-one, multicomponent reaction, nano-[Zn-2BSMP]Cl2, schiff base complex,
solvent-free
Funding information
sayyed jamaleddin asdadabadi university
nanoparticles,[17] ZrOCl2.8H2O, ZrO2, ZrP2O7 NPs,[18] and
[2,20-BPyH][C(CN)3]2.[19]
1
| INTRODUCTION
Newly, to study heterocyclic compounds in many natural
products and their applications in pharmacological chemis-
try, researchers have made many attempts for the synthesis
of similar compounds and their derivatives using multicom-
ponent reactions (MCRs) as an effective protocol in organic
synthesis. MCRs show a remarkable pattern in combinatorial
chemistry by their ability to provide the desired products
with greater efficiency and atom economy by producing
structural complexity in a single step from three or more
reactants.[1–8]
Pyrazolone derivatives are an important group of hetero-
cyclic compounds because of their important antipyretic,[9]
antibactericidal,[10] inflammatory,[11] and herbicidal proper-
ties.[12] Moreover, they have been reported for their antifilar-
ial activities,[13] gastric secretion stimulatory properties,[14]
and also, they are used to treat depression.[15]
Various catalysts were used for the synthesis of
4-((2-hydroxynaphthalen-1-yl)(aryl)methyl)-5-methyl-2-phe-
nyl-1H-pyrazol-3(2H)-ones including PTSA,[16] CuI
Schiff base compounds are widely introduced as one of
the important groups of ligands because of their easy and
convenient protocols for the synthesis and their interesting
coordination chemistry.[20] Lately, we have prepared and
identified a new category of Schiff base complexes by the
reaction of pyranopyrazole derivatives with salicylaldehyde
and different metal salts.[21–25] Herein, in continuing our pre-
vious investigations, we have prepared and characterized
nano-Zn-[2-boromophenyl-salicylaldimine-methylpyrano-
pyrazole]Cl2 (nano-[Zn-2BSMP]Cl2) and applied it, as an
active complex and effective catalyst, for the synthesis of
4-((2-hydroxynaphthalen-1-yl)(aryl)methyl)-5-methyl-2-phe-
nyl-1H-pyrazol-3(2H)-ones (Scheme 1).
2
| RESULTS AND DISCUSSION
Nano-Zn-[2-boromophenyl-salicylaldimine-methylpyranopyr-
azole]Cl2 (nano-[Zn-2BSMP]Cl2) was prepared by the con-
densation of 2-bromobenzaldehyde with ethyl acetoacetate,
© 2018 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2018;1–6.
http://www.jccs.wiley-vch.de
1

2
GOUDARZIAFSHAR ET AL.
SCHEME 1 The preparation of 4-((2-hydroxynaphthalen-1-yl)(aryl)
methyl)-5-methyl-2-phenyl-1H-pyrazol-3(2H)-ones using nano-[Zn-
2BSMP]Cl2
FIGURE 2 SEM micrograph of Nano-[Zn-2BSMP]Cl2
The scanning electron micrographs (SEM) of nano-[Zn-
2BSMP]Cl2 were also obtained, which displayed that parti-
cles were made of size less than 100 nm (Figure 2).
SCHEME 2 The proposed structures of nano-[Zn-2BSMP]Cl2
To optimize the reaction conditions, the condensation of
2-naphthol, 4-chlorobenzaldehyde, phenylhydrazine, and
ethyl acetoacetate was selected as a model reaction. In the
next step, the model reaction was tested in the presence of
various amounts of nano-[Zn-2BSMP]Cl2 in the range of
25–80ꢀC under solvent-free conditions. The best result was
obtained using 5 mol% of nano-[Zn-2BSMP]Cl2 at room
temperature under solvent-free conditions. Increasing the
malononitrile, and hydrazine hydrate to obtain the corre-
sponding pyranopyrazole according to previous literature.[26]
The prepared pyranopyrazole reacted with salicylaldehyde
and ZnCl2 to give Nano-Zn-[2-boromophenyl-salicylaldi-
mine-methylpyranopyrazole]Cl2 (nano-[Zn-2BSMP]Cl2) as a
nano-Schiff base complex (Scheme 2).[25]
Energy-dispersive X-ray spectroscopy (EDX) of nano-
[Zn-2BSMP]Cl2 was conducted and the presence of the
desired elements in the structure of the catalyst, namely
carbon, oxygen, nitrogen, bromine, zinc, and chlorine, was
confirmed. Therefore, the existence of related elements in
nano-[Zn-2BSMP]Cl2 was completely approved by EDX
analysis (Figure 1).[25]
TABLE 1 The effect of the different amounts of the catalyst, types of
solvents, and various temperatures on the reaction of 2-naphthol,
4-chlorobenzaldehyde, phenylhydrazine, and ethyl acetoacetate
Catalyst
Entry (mol%)
Temperature
(ꢀC)
Time
(min)
Yielda
(%)
Solvent
—
1
—
—
2
r.t.
80
r.t.
r.t.
r.t.
60
80
r.t.
r.t.
r.t.
r.t.
r.t.
120
120
30
10
10
10
10
65
15
20
45
30
17
15
10
15
75
90
90
72
65
67
85
75
70
20
69
80
2
—
3
—
4
5
—
5
7
—
6
5
—
7
5
—
8
5
Hexane
H2O
9
5
10
11
12
13
14
5
CH3CN
Ethyl acetate
Acetone
5
5
5
Dichloromethane r.t.
Ethanol r.t.
5
FIGURE 1 Energy-dispersive X-ray spectroscopy (EDX) of Nano-[Zn-
2BSMP]Cl2
a
Isolated yield.

GOUDARZIAFSHAR ET AL.
3
TABLE 2 The synthesis of 4-((2-hydroxynaphthalen-1-yl)(aryl)methyl)-5-methyl-2-phenyl-1H-pyrazol-3(2H)-ones using nano-[Zn-2BSMP]Cl2
Entry
Product
Time (min)
Yielda (%)
M.p. ꢀC (L)
209 (207–209) [19]
1
12
85
2
3
4
13
23
13
85
78
85
183 (183–185) [19]
175–178 (173–175) [19]
200–204 (197–199) [19]
5
6
7
10
25
10
90
73
90
224–228 (225–227) [19]
244–247 (245–247) [19]
220–224 (224–226) [19]
8
9
6
92
80
200–202 (199–201) [19]
20
185–188 (187–189) [19]
10
11
18
20
80
80
147–152 (149–152) [19]
202–203 (203–204) [19]

4
GOUDARZIAFSHAR ET AL.
TABLE 2 (Continued)
Entry
Product
Time (min)
Yielda (%)
M.p. ꢀC (L)
12
17
83
160–162 (157–159) [19]
13
14
15
22
93
85
240–242 (241–243) [19]
192 (197–199) [19]
a
Isolated yield.
reaction time did not improve the yield of product (Table 1).
The model reaction was also tested in various kinds of sol-
vents in comparison with solvent-free conditions, which did
not make much remarkable priority. The catalyst-free condi-
tions were also tested, which did not have much to be
desired in comparison with using of catalyst (Table 1, entries
1 and 2).
To study the generality and scope of nano-[Zn-2BSMP]
Cl2, we have continued our investigation using the catalyst
(5 mol%) with various aromatic aldehydes to afford a series
and separated from the catalyst after filtration. The catalyst
was dried to reuse for another reaction. We observed that the
catalytic activity of the catalyst was restored within the
limits of the experimental errors for four successive runs
(Figure 3).
3
| EXPERIMENTAL
3.1 | General
of
4-((2-hydroxynaphthalen-1-yl)(aryl)methyl)-5-methyl-
All chemicals were purchased from Merck or Fluka Chemical
Companies. The known products were identified by comparison
2-phenyl-1H-pyrazol-3(2H)-ones at room temperature under
solvent-free conditions. Various aromatic aldehydes contain-
ing electron-withdrawing substituents, electron-releasing
substituents, and halogens on their aromatic rings were
tested successfully in this reaction, and gave the desired
products in high yields and in short reaction times (Table 2).
In a plausible mechanism, at first, aromatic aldehyde is
activated by nano-[Zn-2BSMP]Cl2, and then 2-naphthol
attacks on the carbonyl group of the activated aldehyde and
affords intermediate I. Then, orthoquinone methide (o-QM,
II) is prepared after removing one molecule of H2O from
intermediate I. In another part of the mechanism, ethyl acet-
oacetate is activated by nano-[Zn-2BSMP]Cl2 and phenyl
hydrazine attacks on the carbonyl group of the activated
ethyl acetoacetate. Nucleophilic attack by another NH2
group of phenyl hydrazine on the next carbonyl group of
ethyl acetoacetate affords 5-methyl-2,4-dihydropyrazol-
3-one after removing of one molecule of H2O and EtOH,
respectively. Finally, by the Michael addition reaction of
5-methyl-2,4-dihydropyrazol-3-one
with
orthoquinone
methide (o-QM, II), the desired product is prepared after
tautomerization of intermediate III (Scheme 3).
Reusability of the catalyst was also tested on the reaction
of 2-naphthol (1 mmol), 4-chlorobenzaldehyde (1 mmol),
phenylhydrazine (1 mmol), and ethyl acetoacetate (1 mmol).
After completion of the reaction, as monitored by TLC, the
reaction mixture was extracted by warm dry ethyl acetate
SCHEME 3 The proposed mechanism for the synthesis of
4-((2-hydroxynaphthalen-1-yl)(aryl)methyl)-5-methyl-2-phenyl-1H-pyrazol-
3(2H)-ones

GOUDARZIAFSHAR ET AL.
5
added, and the resulting mixture was stirred at room temper-
ature. After completion of the reaction, as monitored by
TLC, warm ethyl acetate was added to the reaction mixture.
The reaction mixture was soluble in warm ethyl acetate and
the catalyst was insoluble in this solvent. The catalyst was
separated from the reaction mixture by filtration and reused
for another reaction. Finally, the crude product was purified
by recrystallization from hexane/ethyl acetate (4:1). The
spectra of compounds have been reported in supporting
information.
4
| CONCLUSIONS
FIGURE 3 The reaction of 2-naphthol, 4-chlorobenzaldehyde,
phenylhydrazine, and ethyl acetoacetate in the presence of nano-[Zn-
2BSMP]Cl2
In summary, we have prepared and characterized nano-[Zn-
2BSMP]Cl2 as an efficient and heterogeneous catalyst for the
one-pot multicomponent synthesis of 4-((2-hydroxynaphthalen-
1-yl)(aryl)methyl)-5-methyl-2-phenyl-1H-pyrazol-3(2H)-ones
by the MCR of various aromatic aldehydes, β-naphthol, ethyl
acetoacetate, and phenyl hydrazine at room temperature under
solvent-free conditions.
of their melting points and spectral data with those reported in
the literature. Progress of the reactions was monitored by TLC
using silica gel SIL G/UV 254 plates.
3.2 | Procedure for the synthesis of nano-Zn-
[2-boromophenyl-salicylaldimine-methylpyranopyrazole]
Cl2 (nano-[Zn-2BSMP]Cl2)
ACKNOWLEDGMENTS
A mixture of 2-bromobenzaldehyde (1 mmol), malononitrile
(0.066 g, 1 mmol), ethyl acetoacetate (0.13 g, 1 mmol)
hydrazine hydrate (1.25 mmol), and isonicotinic acid
(0.1 mmol) (0.0123 g, 10 mol%) was added in a 25 mL
round-bottomed flask connected to a reflux condenser, and
stirred at 100ꢀC. After the completion of the reaction, as
monitored by TLC, the reaction mixture was cooled to room
temperature. Water was added to the reaction mixture to dis-
solve isonicotinic acid and the aqueous layer was separated
from the reaction mixture. Then, the solid residue (crude
product) was triturated by a mixture of ethanol and water
(19/1) to furnish 6-amino-3-methyl-4-(4-nitrophenyl)-2,-
4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile as an amine
and product.[26] The prepared amine (1 mmol) and ZnCl2
(1 mmol) were pulverized in a mortar for 10 min, and then
transferred to a 25 mL round-bottomed flask containing sali-
cylaldehyde (1.5 mmol), connected to a reflux condenser
and stirred at 120ꢀC for 72 hr. After this time, the reaction
mixture was washed by ethylacetate and hexane (9/1) three
times to purify nano-[Zn-2BSMP]Cl2 from excess salicylal-
dehyde (Scheme 2).[25]
The authors gratefully acknowledge the Sayyed Jamaleddin
Asadabadi University for providing support to this work.
ORCID
Hamid Goudarziafshar
https://orcid.org/0000-0002-5930-6253
https://orcid.org/0000-0003-0321-9326
Ahmad Reza Moosavi-Zare
Mehdi Abdolmaleki
https://orcid.org/0000-0002-7950-0942
REFERENCES
[1] J. Zhu, H. Bienayme Eds., Multicomponent Reactions, Wiley, Weinheim
2005.
[2] A. R. Moosavi-Zare, M. A. Zolfigol, M. Daraei, Synlett 2014, 25, 1173.
[3] M. Kangani, N. Hazeri, A. Yazdani-Elah-Abadi, M. Maghsoodlou, J. Chin.
Chem. Soc. 2017, 64, 1259.
[4] A. R. Moosavi-Zare, M. A. Zolfigol, R. Salehi-Moratab, E. Noroozizadeh,
J. Mol. Catal. A: Chem. 2016, 415, 144.
[5] A. R. Moosavi-Zare, M. A. Zolfigol, Z. Rezanejad, Can. J. Chem. 2016,
94, 626.
[6] A. R. Moosavi-Zarea, M. A. Zolfigol, F. Derakhshan-Panah, S. Balalaie,
Mol. Catal. 2018, 449, 142.
[7] A. R. Moosavi-Zare, M. A. Zolfigol, F. Derakhshan-Panah, M. Daraei,
Can. J. Chem. 2015, 93, 1245.
[8] A. R. Moosavi-Zare, M. A. Zolfigol, R. Salehi-Moratab, E. Noroozizadeh,
Can. J. Chem. 2017, 95, 194.
[9] F. R. Souza, V. T. Souaza, V. Ratzlaff, L. P. Borges, M. R. Olivera,
H. G. Bonacorso, N. Zanatta, M. A. Martina, C. F. Mello, Eur. J. Pharm.
2002, 451, 141.
[10] P. N. Dhol, T. E. Achary, A. Nayak, J. Indian Chem. Soc. 1975, 52, 1196.
[11] S. P. Hiremith, K. Rudresh, A. R. Saundan, Indian J. Chem., Sect. B: Org.
Chem. Incl. Med. Chem. 2002, 41, 394.
[12] S. Joerg, G. Reinhold, S. Otto, S. H. Joachim, S. Robert, L. Klaus, Chem.
Abstr. 1988, 108, 167465.
[13] D. M. Bailey, P. E. Hansen, A. G. Hlavac, E. R. Baizman, J. Pearl,
A. F. Defelice, M. E. Feigenson, J. Med. Chem. 1985, 28, 256.
[14] F. Karcı, N. Ertan, Dyes Pigm. 2002, 55, 99.
3.3 | General procedure for the synthesis of
4-((2-hydroxynaphthalen-1-yl)(aryl)methyl)-5-methyl-
2-phenyl-1H-pyrazol-3(2H)-ones using nano-[Zn-
2BSMP]Cl2
To a mixture of 2-naphthol (1 mmol), 4-chlorobenzaldehyde
(1 mmol), phenylhydrazine (1 mmol), and ethyl acetoacetate
(1 mmol) in a 25 mL round-bottomed flask connected to a
reflux condenser, nano-[Zn-2BSMP]Cl2 (5 mol%) was
[15] Y. W. Ho, Dyes Pigm. 2005, 64, 223.

6
GOUDARZIAFSHAR ET AL.
[16] P. Gunasekaran, S. Perumal, P. Yogeeswari, D. Sriram, Eur. J. Med. Chem.
2011, 46, 4530.
[26] M. A. Zolfigol, M. Tavasoli, A. R. Moosavi-Zare, P. Moosavi,
H. G. Kruger, M. Shiri, V. Khakyzadeh, RSC Adv. 2013, 3, 25681.
[17] A. Ziarati, J. Safaei-Ghomi, S. Rohani, Ultrason. Sonochem. 2013, 20,
1069.
[18] J. Safaei-Ghomi, E. Afkhami, H. Shahbazi-Alavi, A. Ziarati, Iran. J. Catal.
2015, 5, 321.
[19] M. A. Zolfigol, N. Mansouri, S. Baghery, Synlett 2016, 27, 1511.
[20] B. Sreenivasulu, Schiff Base and Reduced Schiff Base Ligands, John
Wiley & Sons, Ltd, 2012.
SUPPORTING INFORMATION
Additional supporting information may be found online in
the Supporting Information section at the end of the article.
[21] A. R. Moosavi-Zare, H. Goudarziafshar, S. Dastbaz, J. Chin. Chem. Soc.
2017, 64, 727.
[22] H. Goudarziafshar, A. R. Moosavi-Zare, K. Saki, M. Abdolmaleki, J. Chin.
Chem. Soc. 2017, 64, 1496.
[23] A. R. Moosavi-Zare, H. Goudarziafshar, L. Ghaffari, Appl. Organometal.
Chem. 2017, 31, e3845. https://doi.org/10.1002/aoc.3845.
[24] A. R. Moosavi-Zare, H. Goudarziafshar, K. Saki, Appl. Organometal.
Chem. 2018, 32, e3968. https://doi.org/10.1002/aoc.3968.
[25] A. R. Moosavi-Zare, H. Goudarziafshar, Z. Jalilian, Appl. Organometal.
Chem. 2018, e4584. https://doi.org/10.1002/aoc.4584.
How to cite this article: Goudarziafshar H, Moosavi-
Zare AR, Jalilian Z, Abdolmaleki M. Synthesis of 4-((2-
hydroxynaphthalen-1-yl)(aryl)methyl)-5-methyl-2-phenyl-
1H-pyrazol-3(2H)-ones using nano-Zn-[2-boromophenyl-
salicylaldimine-methylpyranopyrazole]Cl2 nanoparticles.
J Chin Chem Soc. 2018;1–6. https://doi.org/10.1002/jccs.
201800215