Catalytic Synthesis of Chalcones and Pyrazolines Using Nanorod Vanadatesulfuric Acid: An Efficient and Reusable Catalyst

Article abstract of DOI:10.1002/jccs.201600157

Nanorod vanadatesulfuric acid (VSA NRs), as a recyclable and ecologically benign catalyst, was used for the one-pot synthesis of chalcones and 1,3,5-triaryl-2-pyrazolines (TAPs). Chalcones were prepared via the condensation of substituted acetophenones with aryl-aldehydes under solvent-free conditions. Subsequently, the synthesized chalcones were used for the catalytic synthesis of TAPs via two-component condensation with phenyl hydrazine in refluxing ethanol. VSA is easily prepared by a simple reaction of chlorosulfonic acid and sodium metavanadate of high purity. Compared to conventional procedures, the present protocol offers several advantages such as simplicity of the procedure, appropriate reaction times, high to excellent yields, easily work-up, recoverability, and reusability of the catalyst, and simple purification of the products.

Full text of DOI:10.1002/jccs.201600157

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Catalytic Synthesis of Chalcones and Pyrazolines Using Nanorod Vanadatesulfuric
Acid: An Efficient and Reusable Catalyst
*
Masoud Nasr-Esfahani, Mona Daghaghale and Mahbube Taei
Department of Chemistry, Yasouj University, Yasouj 75918-74831, Iran
(Received: April 27, 2016; Accepted: September 18, 2016; DOI: 10.1002/jccs.201600157)
Nanorod vanadatesulfuric acid (VSA NRs), as a recyclable and ecologically benign catalyst, was
used for the one-pot synthesis of chalcones and 1,3,5-triaryl-2-pyrazolines (TAPs). Chalcones were
prepared via the condensation of substituted acetophenones with aryl-aldehydes under solvent-free
conditions. Subsequently, the synthesized chalcones were used for the catalytic synthesis of TAPs
via two-component condensation with phenyl hydrazine in refluxing ethanol. VSA is easily pre-
pared by a simple reaction of chlorosulfonic acid and sodium metavanadate of high purity. Com-
pared to conventional procedures, the present protocol offers several advantages such as simplicity
of the procedure, appropriate reaction times, high to excellent yields, easily work-up, recoverabil-
ity, and reusability of the catalyst, and simple purification of the products.
Keywords: Chalcones; 1,3,5-Triaryl-2-pyrazolines; Solvent-free; Nanoatalyst;
Vanadatesulfuric acid.
INTRODUCTION
Chalcones (1,3-diaryl-2-propene-1-ones) are natural
inhibitory (8),43 muscle relaxant, psychoanaleptic,
antihypertensive,44 cytotoxic, platelet aggregation
inhibiting,45 and anti-pyretic.46 In addition, they possess
photoluminiscence (9)47 and can act as polarity
probes (10).48
Chalcones are synthesized using base-catalyzed or
acid-catalyzed claisen-Schmidt condensation of substi-
tuted acetophenones with aryl-aldehydes, followed by
dehydration to yield chalcones.49 Several catalysts have
been developed for the preparation of chalcone deriva-
tives, including NaOH–Al2O,1 zirconium chloride,12
silica–H2SO4, ultrasound,5 and NaOH.7
substances found in abundance in numerous species of
plants, or can be synthesized.1 These compounds display the
variety of biological activities such as anti-inflammatory,2
antipyretic,3 antimutagenic,4 antimalarial,5 antitumor,6
vasodilatory,7 analgesic,8 antiplatelet,9 inhibition of leukotri-
ene B,10 antiviral,11 antileishmanial,12 immunomodulatory,13
antihyperglycemic,14
antiangeogenic,15
antifungal,16
antibacterial,17 inhibition of chemical mediator release,18 ant-
ulcer,19 antimitotic,1 anti-invasive, anticancer,20 inhibition of
tyrosinase,21 and inhibition of aldose reductase22 activities. In
addition, chalcones are well-known intermediates for the syn-
thesis of various heterocyclic compounds1 like quinolinones,
isoxazoles, benzofuranones, thiadiazines, tetrahydro-2-chro-
mens, benzodiazepines,23 and pyrazolines.24
Among the various pyrazoline isomers, 1,3,5-
triaryl-2-pyrazolines (TAPs) seem to be the most fre-
quently investigated compounds.50 Diverse methods
have been reported for the preparation of this group of
compounds.44 From the nineteenth century, the reac-
tion of chalcone with hydrazine in refluxing acetic acid
became the main method for the synthesis of 2-pyrazo-
lines.25 Several catalysts such as the hot acetic acid
solution,51 sodium acetate–acetic acid aqueous solution
Pyrazoline derivatives also possess prominent biolog-
ical and pharmacological activities, e.g., tranquillizing,25
antinociceptive (1),26 antidepressant,27 antiepileptic (2),28
anticonvulsant,29 anti-inflammatory (3),30 antimicrobial
(4),31 antifungal,32 antimycobacterial (5),33 anticancer,34
antitubercular,35 antiamoebic,36 MAO-inhibitory (6),37
insecticidal,38 hypotensive,39 amine oxidase inhibitory,40
cholesterol inhibitory,41 antioxidant (7),42 COX-2
under ultrasound irradiation,44 H3PW12O40, K2CO3-
52
mediated microwave irradiation,53 γ-Fe2O3@SiO2-
PW12 nanoparticles,54 and acetic acid under ultrasound
*Corresponding author. Email: manas@mail.yu.ac.ir; m_nasr_e@yahoo.com
J. Chin. Chem. Soc. 2016
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Article
Nasr-Esfahani et al.
S
H3CO
OCH3
H
H
N
OCH3
O
N
N
H
N
N
N
N
N
N
S
O
O
HN
(1)
(2)
(3)
Cl
SO2NH2
N
F
H
H
N
O
N
Cl
O
N
N
N
N
N
S
Cl
NO2
(5)
(6)
(4)
CF3
O
N
N
N
N
OCH2CO2H
N
N
N
O
H
O2N
SO2NH2
(7)
(8)
(9)
H3CO
O
O
N
N
OH
(10)
irradiation25 have been used for the preparation of pyr-
azoline derivatives.
chalcones were used as suitable precursors for the
catalytic synthesis of TAPs (Scheme 2).
From the green chemistry view point, multicom-
ponent reactions (MCRs) have been proven to be pow-
erful and efficient bond-forming tools in organic,
medicinal, and combinatorial chemistry.55 In this
direction, solid acid catalysts have attracted increasing
attention in organic syntheses because of their advan-
tages including simplicity, reusability, low cost, non-
toxicity, and ease of isolation after completion of the
reaction.56
RESULTS AND DISCUSSION
VSA NRs were prepared via the reaction between
sodium metavanadate and chlorosulfonic acid (1:1 mole
ratio) in dry CHCl3 (Scheme 3).
Based on transmission electron microscopy
(TEM) images, the solid acid catalyst has a needle-like
morphology with a narrow size distribution in the range
of 15–20 nm and a mean size of 17 nm, confirming the
In continuation of our previous efforts toward the
development of application of new nano-structured
heterogeneous catalysts in organic synthesis,57,58 in
the present work we first report the solvent-free synthe-
sis of chalcones in the presence of nanorod vanadatesul-
furic acid (VSA NRs) (Scheme 1). Subsequently, the
O
O
R
O2VOSO3H
H
CH3
+
70 °C
R1
R1
R
O
Solvent-free
(11)
Scheme 1. VSA-assisted synthesis of chalcones.
2
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Catalytic Synthesis of Chalcones and Pyrazolines Using Nanorod Vanadatesulfuric Acid
including refluxing in various solvents and also under
solvent-free classical heating conditions.
R1
R
R
O2VOSO3H
EtOH, reflux
Ph
NH2
+
N
N
N
R1
H
The best conditions for the preparation of chalcons
were achieved when 1 mmol benzaldehyde, 1 mmol
acetophenone, and 0.15 mmol VSA were used under
solvent-free conditions. These conditions were applied for
synthesizing a series of substituted chalcones (Table 3).
The results in Table 2 show that the reaction using
0.10 mmol of the catalyst in the presence of ethanol as
solvent and under reflux conditions afforded products
in excellent yield. The scope and generality of this
method were well demonstrated using structurally
diverse chalcones and phenylhydrazines. The results are
summarized in Table 4.
From Table 4, it is seen that though the reactions
proceed well with all substrates, those with electron-
withdrawing groups in the aromatic ring of benzaldehyde
give slightly increased rates. In addition, the presence of
electron-donor groups in the aryl methyl ketone
decreased the yields, presumably because of the ease of
formation of the corresponding enolate anion.
From Table 4, it can also be seen that the reac-
tions proceed well with all substrates, but substrates
with electron-withdrawing groups (R-substituent) such
as NO2 and Cl are generally less reactive than those
with electron-donating groups (OCH3 and CH3).
Furthermore, a substrate with two formyl groups
such as isophthaldehyde (Table 3, Entry 7) produced
the corresponding bis-chalcone and followed by bis-
pyrazoline (Table 4, Entry 7) in reasonable times and
good yields (Scheme 4).
Ph
(12)
O
Scheme 2. Catalytic synthesis of 1,3-5-triaryl-2-
pyrazolines.
Scheme 3. Synthesis of nanorod vanadatesulfuric acid.
data calculated from Scherrer’s equation from X-ray
diffraction (XRD) pattern of VSA NRs (Figure 1).58
The condensation reaction of benzaldehyde and
acetophenone was selected as a model reaction for the
synthesis of chalcones (Table 1). Also, the reaction of
1,3-diphenyl-2-propen-1-one with phenylhydrazine
was used as a model reaction for the synthesis of
2-pyrazolines (Table 2). The optimization of conditions
of the reactions was done using different amounts of
VSA at various temperatures under different conditions
CATALYST RECOVERY
The recyclability of VSA was investigated for the
reaction of benzaldehdye and acetophenone as a model
for synthesis of chalcones, and the reaction of 1,3-
diphenyl-2-propen-1-one with phenylhydrazine as a
model reaction for synthesis of 2-pyrazolines. After
completion of reaction, the separated catalyst could be
reused after washing with ethanol and drying at 100ꢀC
for 2 h. This recycled catalyst was used for the subse-
quent catalytic runs. The structural stability of the
recovered catalyst had been previously been determined
by XRD, TEM, and Fourier transform infrared (FT-
IR) spectroscopy.58 The catalytic system worked well
up to four catalytic runs, and no appreciable change in
activity was noticed after four cycles (Figure 2).
Fig. 1. TEM image of VSA NRs.
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Article
Nasr-Esfahani et al.
Yield2 (%)
Table 1. Effect of different conditions in the reaction of benzaldehyde and acetophenone
Entry1
Catalyst (mol%)
Temperature (ꢀC)
Solvent
Time (h)
1
2
3
4
5
6
7
8
5
10
15
20
15
15
15
15
15
15
15
70
70
70
—
—
7
6
5
5
7
8
7
10
7
6
75
80
95
95
85
80
75
53
70
85
73
—
70
—
Reflux
Reflux
Reflux
RT
60
80
EtOH
MeOH
CHCl3
—
9
—
10
11
90
8
1 Entry in bold indicate the optimum conditions; 2 Isolated yields.
Table 2. Condition optimization in the condensation reaction of 1,3-diphenyl-2-propen-1-one with phenylhydrazine
Entry1
Catalyst (mol%)
Temperature (ꢀC)
Solvent
Time (h)
Yield2 (%)
1
2
3
4
5
6
7
5
10
15
10
10
10
10
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
70
EtOH
EtOH
EtOH
H2O
CHCl3
MeOH
—
9
5
5
7
7.5
7
8
60
95
80
78
60
80
50
1 Entry in bold indicate the optimum conditions; 2 Isolated yields.
Table 3. Synthesis of chalcone derivatives in the presence of VSA NRs
O
R
O
H
O2VOSO3H
70 oC
Solvent-free
CH3
+
R1
R
1
(11)
O
Mp (ꢀC)
Entry
R1
R
Product
Time (h)
Yield1 (%)
Found
Reported
1
2
3
4
5
6
7
8
9
10
11
12
1
H
H
H
H
H
H
11a
11b
11c
11d
11e
11f
11g
11h
11i
5
5
6
4
7
4
7
7.5
3
95
97
89
95
88
97
88
78
85
80
85
85
55–57
155–157
40–43
110–113
74–76
56–5720
157–15910
42–4759
110–11260
7610
4-NO2
4-Me
4-Cl
4-OMe
2,4-Cl
3-CHO
4-OMe
H
H
H
97–99
9860
138–141
100–102
99–101
122–124
128–131
152–154
—
4-OMe
4-Cl
4-Cl
4-Cl
4-Br
93–9461
99–1015
119–1205
—
4-OMe
3-Me
H
11j
11k
11l
5
4
3
155–1577
Isolated yields.
4
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Catalytic Synthesis of Chalcones and Pyrazolines Using Nanorod Vanadatesulfuric Acid
Table 4. Synthesis of pyrazolines using VSA nanocatalyst and in presence of ethanol as solvent under reflux conditions
R1
R
R
O2VOSO3H
EtOH, reflux
Ph
NH2
N
H
+
N
R1
N
Ph
(12)
Mp (ꢀC)
Reported
Entry
R1
R
Product
Time (h)
Yield1 (%)
Found
1
2
3
4
5
6
7
8
H
H
H
H
H
C6H5
4-NO2
4-Me
4-Cl
4-OMe
2,4-Cl
3-CHO
4-OMe
H
12a
12b
12c
12d
12e
12f
12g
12h
12i
5
6
3.5
5
3
4
6
6
2
3
2
3
3
95
85
96
85
98
83
85
90
98
95
98
95
98
131–133
133–136
130–132
130–135
114–116
123–125
228–230
145–148
143–145
156–160
148–150
144–145
168–169
130–13250
136–13850
128–13052
133–13451
110–11244
127–12952
—
139–14125
143–14552
158–15925
—
H
H
4-OMe
4-Cl
4-Cl
4-Cl
4-Br
4-Br
9
10
11
12
13
1
4-OMe
3-Me
H
12j
12k
12l
144–14752
4-Me
12m
—
Isolated yields.
100
95
90
85
80
75
70
O
95% , 5 h
95 %, 5h
O
92%, 7 h
O
90%, 8 h
95%, 5 h
88% , 8 h
O2VOSO3H
H
CH3
+
2
70 °C
a
Solvent-free
88%, 6h
O
H
O
85%, 7 h
b
Ph
80%, 8 h
80%, 8 h
NH
NH2
Fresh
1
2
3
4
Reaction cycles
Ph
Fig. 2. Reusability of VSA NRs in the synthesis of
chalcones (a) and 2-pyrazolines (b).
N
N
N
N
Ph
in a one-pot, two-component condensation of substi-
tuted acetophenones with aryl-aldehydes under solvent-
free conditions. Subsequently, the synthetic chalcones
were used for the catalytic synthesis of TAP in a one-
pot, two-component condensation with phenyl hydra-
zine in refluxing ethanol. This method provided the
desired products in high to excellent yields in appropri-
ate reaction times, following a simple work-up process.
Scheme 4. Synthesis of bis-chalcone and bis-
pyrazoline.
CONCLUSION
In summary, we have developed procedures using
VSA NRs as an efficient and novel catalyst for the syn-
thesis of chalcones and TAPs. Chalcones were prepared
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Nasr-Esfahani et al.
Furthermore, the catalyst could be readily recycled and
reused at least four times without any considerable loss
of its activity and change in the structure. Moreover,
this catalytic system demonstrates advantages such as
environmentally benign character, mild reaction condi-
tions, easy handling, lower catalyst loading, and cost
efficiency. This approach can make a valuable contribu-
tion to the reported processes in the field of chalcones
and pyrazolines syntheses.
chromatography (TLC). After completion of the reac-
tion, the obtained mixture was dissolved in hot ethanol
and filtered to remove the catalyst. The filtrate was con-
centrated, and the obtained precipitates were recrystal-
lized from a suitable solvent to afford the pure product.
The products were identified by comparison with physi-
cal and spectral data given in the literature.
3,30-(1,4-Phenylene)-bis (1-phenyl-2-propene-1-one) (11g)
M.p. 138–141ꢀC; IR (KBr): ν = 3058, 1662, 1604,
1276, 1211, 1018, 765 cm−1 1H NMR (400 MHz,
;
EXPERIMENTAL
Materials and methods
DMSO-d6): δ = 7.57–7.74 (m, 3H), 7.70–7.74 (m, 1H),
7.83 (d, J = 15.6 Hz, 1H), 7.99 (dd, J1 = 4.8 Hz,
J2 = 1.6 Hz, 1H), 8.10 (d, J = 16.0 Hz, 1H), 8.19–8.22
(m, 2H), 8.50 (s, 1H) (Fig. S2); 13C NMR (100 MHz,
DMSO-d6): 123.35, 128.91, 129.10, 129.35, 129.39, 130.04,
131.47, 133.79, 135.87, 137.95, 143.88, 189.72 (Fig. S1).
All chemicals used for the syntheses were pur-
chased from Merck, Fluka, and Aldrich chemical com-
panies. Infrared (IR) spectra were recorded on an FT-
IR JASCO-680 spectrometer. Melting points were
determined in open capillary tubes using a Barnstead
Electrothermal (BI9300) apparatus and are uncorrected.
Nuclear magnetic resonance (NMR) spectra were
recorded using a Bruker Ultrashield spectrometer at
400 MHz (1H) and 100 MHz (13C) using DMSO-d6 as
the solvent and TMS as the internal standard.
1-(4-Chlorophenyl)-3-(3-methylphenyl)-2-propen-1-
one (11k)
M.p. 128–131ꢀC; IR (KBr): ν = 3012, 2962, 1656,
1602, 1490, 1176, 759 cm−1 1H NMR (400 MHz,
;
DMSO-d6): δ = 2.37 (s, 3H), 7.30 (d, J = 7.6 Hz, 1H),
7.37 (t, J = 7.6 Hz, 1H), 7.64–7.69 (m, 3H), 7.75 (d,
J = 15.6 Hz, 2H), 7.93 (d, J = 15.6 Hz, 1H), 8.17–8.23
(m, 2H) (Fig. S4); 13C NMR (100 MHz, DMSO-d6):
21.34, 121.96, 126.93, 129.31, 129.38, 129.72, 130.93, 132.00,
134.96, 136.70, 138.60, 138.68, 145.16, 188.56 (Fig. S3).
Synthesis of nanorod vanadatesulfuric acid
The sample of VSA was prepared as follows:
sodium metavanadate monohydrate (NaVO3.H2O,
MW = 13994) was dried in the oven at 200ꢀC for 4 h
to produce anhydrous sodium metavanadate. To chlor-
osulfonic acid (7.7 mL, 0.1 mol, 11.6 g) in a 250 mL
round bottom flask in an ice bath, anhydrous sodium
metavanadate (0.1 mol, 12.2 g) was added gradually
with stirring. After completion of the addition, the reac-
tion mixture was stirred for 1 h. Then 50 mL of cold
water was added to the reaction mixture, which was
shaken for 10 min. Finally, vanadatesulfuric acid as a
dark red solid was separated from the mixture after fil-
tration. Yield: 91%, mp: 256ꢀC (dec.); characteristic IR
bands (KBr, cm−1): 3540–3300 (OH, bs), 1640 (OH,
m), 1250–1140 (S = O, bs), 1050 (S–O, m), 960 (V = O,
m), 840 (V = O, m), 630 (V–O, m).
Synthesis of 1,3,5-triphenyl-2-pyrazolines
A typical method for the catalytic synthesis of
TAP is depicted in Scheme 3. A mixture of chlorochal-
cone (11a–l, 1 mmol), phenylhydrazine (1 mmol), and
ethanol (5 mL) was heated at reflux for an appropriate
time. At the end of the reaction, the reaction mixture
was filtered to separate the catalyst. The catalyst was
easily recovered quantitatively by simple filtration. The
filtrate was evaporated and the crude product was puri-
fied by crystallization in EtOH.
Bis-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-5-yl)-
benzene (12g)
General procedure for the preparation of chalcones
A mixture of substituted benzaldehydes (1 mmol,),
acetophenone derivatives (1 mmol), and vanadatesulfu-
ric acid (0.15 mmol) was stirred at 70ꢀC for an appro-
priate time under solvent-free condition. The progress
of the reaction was monitored by thin-layer
M.p. 228–230ꢀC; IR (KBr): ν = 3062, 1600, 1504,
1
1490, 1392, 755, 744, 690 cm−1; H NMR (400 MHz,
DMSO-d6): δ = 3.09 (dd, J1 = 12.0 Hz, J2 = 6.8 Hz,
1H), 3.92 (dd, J1 = 15.0 Hz, J2 = 12.4 Hz, 1H), 5.46
(dd, J1 = 9.4 Hz, J2 = 6.8 Hz, 1H), 6.73 (t, J = 7.2 Hz,
1H), 7.04 (d, J = 9.6 Hz, 2H), 7.11–7.15 (m, 3H), 7.29
6
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Catalytic Synthesis of Chalcones and Pyrazolines Using Nanorod Vanadatesulfuric Acid
5. A. Lahyani, M. Chtourou, M. H. Frikha, M. Trabelsi,
J. Adv. Chem. 2014, 10, 2874.
(t, J = 7.8 Hz, 1H), 7.37–7.47 (m, 4H), 7.74–7.76 (m,
2H) (Fig. S6); 13C NMR (100 MHz, DMSO-d6): 43.44,
63,83, 72.19, 113.58, 119.22, 125.31, 126.21, 129.15, 129.25,
129.28, 130.37, 132.71, 143.79, 144.85, 147.82 (Fig. S5).
6. R. De Vincenzo, C. Ferlini, M. Distefeno, C. Gaggini,
A. Riva, E. Bombardelli, P. Morazzini, F. Belluti,
F. O. Ranelletti, S. Mancuso, Cancer Chemother. Phar-
macol. 2000, 46, 305.
3-(4-Chlorophenyl)-5-(3-methylphenyl)-1-phenyl-2-
pyrazoline (12k)
7. A. Choudhary, V. Juyal, Int. J. Pharm. Pharm. Sci. 2011,
3, 125.
8. G. S. Viana, M. A. Bandeira, F. Matos, J. Phytomed.
2003, 10, 189.
M.p.148–150ꢀC; IR (KBr): 3027, 2919, 1596,
1
1490, 1386, 1322, 1126, 1089, 786, 744, 688 cm−1; H
NMR (400 MHz, DMSO-d6): δ = 2.28 (s, 3H), 3.10
(dd, J1 = 7.6 HZ, J2 = 6.8 HZ, 1H), 3.92 (dd, J1 = 16
HZ, J2 = 12.4 HZ, 1H), 5.45 (q, J = 6.8 HZ, 1H), 6.75
(t, J = 6.8 HZ, 1H), 7.02 (dd, J1 = 8.8 HZ, J2 = 4.8
HZ, 2H), 7.14–7.19 (m, 3H), 7.24 ( t, J = 7.4 HZ, 1H),
7.48–7.52 (m, 2H), 7.75–7.79 (m, 2H) (Fig. S8); 13C
NMR (100 MHz, DMSO-d6): 21.57, 43.38, 63.88, 113.47,
119.29, 123.39, 126.74, 127.82, 128.66, 129.18, 129.38,
131.69, 133.54, 138.73, 143.01, 144.60, 146.61 (Fig. S7).
9. L. M. Zhao, H. S. Jin, L. P. Sun, H. R. Piao, Z. S. Quan,
Bioorg. Med. Chem. Lett. 2005, 15, 5027.
10. N. Raghav, P. Malik, Adv. Appl. Sci. Res. 2011, 2, 410.
11. J.
C.
Onyilagna,
B.
Malhotra,
M.
Elder,
G. H. N. Towers, Can. J. Plant Pathol. 1997, 19, 133.
12. K. Akanksha, J. Mol. Catal. A: Chem. 2007, 274, 212.
13. L. Barford, K. Kemp, M. Hansen, A. Kharazmi, Int.
Immunopharmacol. 2002, 2, 545.
14. M. Satyanarayana, P. Tiwari, K. Tripathi, A. K. Srivastava,
R. Pratap, Bioorg. Med. Chem. 2004, 12, 883.
15. A. Boumendjel, X. Ronot, J. Boutonnat, Curr. Drug Tar-
gets 2009, 10, 363.
16. G. G. Duthie, J. A. M. Kyle, S. J. Duthie, Nutr. Res.
Rev. 2000, 13, 79.
17. S. D. Nimbalkar, Int. J. Adv. Res. 2015, 3, 516.
18. H. H. Ko, L. T. Tsao, K. L. Yu, C. T. Liu, J. P. Wang,
C. N. Lin, Bioorg. Med. Chem. 2003, 11, 105.
3-(4-Bromophenyl)-5-(4-methylphenyl)-1-phenyl-2-
pyrazoline (12m)
M.p. 168–169ꢀC; IR (KBr): 3016, 1598, 1502,
1
1488, 1384, 1126, 823, 744 cm−1; H NMR (400 MHz,
DMSO-d6): δ = 2.27 (s, 3H), 3.09 (dd, J1 = 17.6 HZ,
J2 = 6.4 HZ, 1H), 3.90 (dd, J1 = 16.0 HZ, J2 = 12.4
HZ, 1H), 5.48 (q, J = 6.4 HZ, 1H), 6.74 (t, J = 7.2
HZ, 1H), 7.02 (dd, J1 = 8.8 HZ, J2 = 0.8 HZ, 2H),
7.14–7.20 (m, 6H), 7.62–7.65 (m, 2H), 7.68–7.71 (m,
2H) (Fig. S10); 13C NMR (100 MHz, DMSO-d6): 21.13,
63.58, 113.53, 119.27, 122.17, 126.28, 128.04, 129.35,
130.04, 132.08, 137.11, 139.88, 144.47, 146.64 (Fig. S9).
19. S. Mukarami, M. Muramatsu, H. Aihara, S. Otomo, Bio-
chem. Pharmacol. 1991, 42, 1447.
20. S. Syam, S. I. Abdelwahab, M. A. Al-Mamary,
S. Mohan, Molecules 2012, 17, 6179.
21. S. Khatib, O. Nerya, R. Musa, M. Shmnel, S. Tamir,
J. Vaya, Bioorg. Med. Chem. 2005, 13, 433.
22. F. Severi, S. Benvenuti, L. Costantino, G. Vampa,
M. Melegari, L. Antolini, Eur. J. Med. Chem. 1998,
33, 859.
ACKNOWLEDGMENT
This work was partially supported by Yasouj
University.
23. S. R. Sarda, V. A. Puri, A. B. Rode, T. N. Dalawe,
W. N. Jadhav, R. P. Pawar, ARKIVOC 2007, 16, 242.
24. P. M. Sivakumar, S. Ganesan, P. Veluchamy, M. Doble,
Chem. Biol. Drug Des. 2010, 76, 407.
25. Z. P. Lin, J. T. Li, J. Chem. 2012, 9, 267.
26. R. Fazaeli, H. Aliyan, S. Mallakpour, Z. Rafiee,
M. Bordbar, Chin. J. Catal. 2011, 32, 582.
Supporting information
Supporting information for this article is available
on the www under 10.1002/jccs.201600157.
27. Y. R. Prasad, A. L. Rao, L. Prasoona, K. Murali,
P. R. Kumar, Bioorg. Med. Chem. Lett. 2005, 15, 5030.
28. Z. Ozdemir, H. B. Kandilci, B. Gümüs¸xel, U. Calis¸,
A. A. Bilgin, Eur. J. Med. Chem. 2007, 42, 373.
29. S. P. Singh, A. Chaudhari, J. P. Barthwal, S. S. Parmar,
Anticonvulsant Activity and Selective Inhibition of Nicotin-
amide Adenine Dinucleotide-dependent Oxidations by
1,3,5-Trisubstituted Pyrazolines, Wiley Interscience, J.
Pham. Sci. 1974, 63, 1948.
REFERENCES
1. S. R. Sarda, W. N. Jadhav, S. R. Bhusare,
S. K. Wasmatkar, S. A. Dake, R. P. Pawar, Int. J. Chem.
Tech. Res. 2009, 1, 265.
2. Z. Nowakowska, Eur. J. Med. Chem. 2007, 42, 125.
3. A. Sultan, A. R. Raza, M. Abbas, M. K. Khan,
M. N. Tahir, N. Saari, Molecules 2013, 18, 10081.
4. T. Torigoo, M. Arisawa, S. Iloch, M. Fujiu,
H. B. Mayuyama, Biophys. Res. Commun. 1983, 112, 833.
J. Chin. Chem. Soc. 2016
© 2016 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
7

Article
Nasr-Esfahani et al.
30. I. G. Rathish, K. Javed, S. Ahmad, S. Bano, M. S. Alam,
K. K. Pillai, S. Singh, V. Bagchi, Bioorg. Med. Chem.
Lett. 2008, 21, 212.
31. N. M. Abunada, H. M. Hassaneen, N. G. Kandile,
O. A. Miqdad, Molecules 2008, 13, 1011.
32. B. A. AbdelWahab, H. A. AbdelAziz, E. M. Ahmed,
Eur. J. Med. Chem. 2008, 43, 1.
33. M. G. Mamolo, D. Zampieri, V. Falagiani, L. Vio,
E. Banfi, IL Farmaco 2001, 56, 593.
47. M. Wanga, J. Zhanga, J. Liu, C. Xu, H. Ju, J. Lumines.
2002, 99, 79.
48. D. A. Svechkarev, I. V. Bukatich, A. O. Doroshenko,
J. Photchem. Photobiol. A. Chem. 2008, 200, 426.
49. C. B. Patil, S. K. Mahajan, S. A. Katti, J. Pharm. Sci.
Res. 2009, 1, 11.
50. R. Fazaeli, H. Aliyan, S. Tangestaninejad, E. Mohammadi,
M. Bordbar, Chin. J. Catal. 2012, 33, 237.
51. A. Levai, ARKIVOC 2005, 9, 344.
34. F. Manna, F. Chimenti, R. Fioravanti, A. Bolasco,
D. Secci, P. Chimenti, C. Ferlini, G. Scambi, Bioorg.
Med. Chem. Lett. 2005, 15, 4632.
35. V. H. Babu, S. K. Manna, Sneha, K. K. Srinivasan,
G. V. Bhatt, Ind. J. Het. Chem. 2004, 13, 253.
36. A. Budakoti, A. R. Bhat, F. Athar, A. Azam, Eur.
J. Med. Chem. 2008, 43, 1749.
37. F. Chimenti, R. Fioravanti, A. Bolasco, F. Manna,
P. Chimenti, D. Secci, F. Rossi, P. Turini, F. Ortuso,
S. Alcaro, M. C. Cardia, Eur. J. Med. Chem. 2008,
43, 2262.
38. K. S. Silver, D. M. Soderlund, Pestic. Biochem. Physiol.
2005, 81, 136.
39. M. D. Azizur Rahman, A. A. Siddiqui, Int. J. Pharma.
Sci. Drug Res. 2010, 2, 165.
40. F. Manna, F. Chimenti, A. Bolasco, D. Secci, B. Bizzarri,
O. Befani, P. Turini, B. Mondovi, S. Alcaroc, A. Tafid,
Bioorg. Med. Chem. Lett. 2002, 12, 3629.
41. T. S. Jeong, K. S. Kim, S. J. An, K. H. Cho, S. Lee,
W. S. Lee, Bioorg. Med. Chem. Lett. 2004, 14, 2715.
42. V. H. Babu, C. Sridevi, A. Joseph, K. K. Srinivasan, Ind.
J. Pharm. Sci. 2008, 69, 470.
43. M. V. R. Reddy, V. K. Billa, V. R. Pallela,
M. R. Mallireddigari, R. Boominathan, J. L. Gabriel,
E. P. Reddy, Bioorg. Med. Chem. 2008, 16, 3907.
44. J. T. Li, X. H. Zhang, Z. P. Lin, Beilstein J. Org. Chem.
2007, 3, 13.
52. R. Fazaeli, H. Aliyan, M. Bordbarand, E. Mohammadi,
Open Catal. J. 2010, 3, 79.
53. M. Kidwai, S. Kukreja, R. Thakur, Lett. Org. Chem.
2006, 3, 135.
54. H. Aliyan, R. Fazaeli, N. Tajsaeed, Iran. J. Catal. 2013,
3, 99.
55. (a) P. Lu, Y. G. Wang, Synlett 2010, 165; (b) B. Ganem,
Acc. Chem. Res. 2009, 42, 463; (c) A. Domling, Chem.
Rev. 2006, 106, 17; (d) D. J. Ramon, M. Yus, Angew.
Chem. Int. Ed. Engl. 2005, 44, 1602; (e) R. V. A. Orru,
M. de Greef, Synthesis 2003, 10, 1471; (f ) I. Ugi,
S. Heck, Comb. Chem. High Temp. Scr. 2001, 4, 1;
(g) L. Weber, K. Illgen, M. Almstetter, Synlett
1999, 366.
56. J. H. Clark, Acc. Chem. Res. 2002, 35, 791.
57. M. Nasr-Esfahani, M. Taei, RSC Adv. 2015, 5, 44978.
58. (a) M. Nasr-Esfahani, T. Abdizadeh, J. Nanosci. Nano-
technol. 2013, 13, 5004; (b) M. Nasr-Esfahani,
M. Montazerozohori, T. Abdizadeh, Chem. Pap. 2015,
69, 1491; (c) M. Nasr-Esfahani, M. Montazerozohori,
T. Abdizadeh, C. R. Chim. 2015, 18, 547.
59. G. Thirunarayanan, K. Thirumurthy, G. Vanangamudi,
M. Subramanian, R. Arulkumaran, D. Kamalakkannan,
R. Sundararajan, S. P. Sakthinathan, S. Vijayakumar,
K. Ran-ganathan, R. Suresh, Elixir Org. Chem. 2012,
45, 7898.
60. M. Y. Shandala, A. M. Hamdy, Nat. J. Chem. 2008,
30, 338.
61. M. G. Ahmed, U. K. R. Romman, S. M. Ahmed,
K. Akhter, M. d. E. Halim, Bangladesh J. Sci. Ind. Res.
2007, 42, 45.
45. A. Hasan, A. Abbas, M. N. Akhtar, Molecules 2011,
16, 7789.
46. A. Gharib, N. Noroozi Pesyan, L. Vojdani Fard,
M. Roshani, Front. Heterocycl. Chem. 2015, 1, 6.
8
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