A convenient and efficient protocol for the synthesis of 1,3,5-triaryl-2-pyrazolines in acetic acid under ultrasound irradiation

Article abstract of DOI:10.1155/2012/364798

1,3,5-Triaryl-2-pyrazolines were synthesized in acetic acid in high yields within 60-180 min under ultrasound irradiation at room temperature.

Full text of DOI:10.1155/2012/364798

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2012, 9(1), 267-271
http://www.e-journals.net
A Convenient and Efficient Protocol for the
Synthesis of 1,3,5-Triaryl-2-pyrazolines in
Acetic Acid under Ultrasound Irradiation
ZHI-PING LIN* and JI-TAI LI
*Department of Biology and Chemistry
Baoding University, Baoding -071000, P. R. China
College of Chemistry and Environmental Science
Hebei University, Baoding -071002, P. R. China
zhiping888999@yahoo.com.cn
Received 12 April 2011; Accepted 2 July 2011
Abstract: 1,3,5-Triaryl-2-pyrazolines were synthesized in acetic acid in high
yields within 60-180 min under ultrasound irradiation at room temperature.
Keywords: 1,3,5-Triaryl-2-pyrazolines, Acetic acid, Synthesis, Ultrasound irradiation
Introduction
Pyrazoline derivatives have been found to possess a broad spectrum of biological activities
such as tranquillizing, muscle relaxant, psychoanaleptic, anticonvulsant, antihypertensive,
and antidepressantactivities1-6. As a new type of highly active insecticide, pyrazolines had
very high activity towards coleopteran and lepidopteran insects7. The results of preliminary
bioassay indicated that some of the compounds showed fungicidal and plant growth
regulatory activities8. Benzothiazole compounds with byrazoline group or benximidazole
group are new fluorescent compounds. The fluorescent compounds have been used in many
fields, but their development has been slow9,10. The results from Zhang group indicate that
the fluorescence quantum yield of compound with methoxy group is higher than that of
compound with the substituents of N,N-dimethlyamino group11.
Among of various pyrazoline derivatives, 2-pyrazolines seem to be the most frequently
studied pyrazoline type compounds. A variety of methods have been reported for the
preparation of this class of compounds. From 19th century, the reaction of α,β-unsaturated
aldehydes and ketones with phenylhydrazine in acetic acid by refluxing became one of the
most popular methods for the preparation of 2-pyrazolines12. Ultrasound has increasingly
been used in organic synthesis in the last three decades. A large number of organic
reactions can be carried out in higher yields, shorter reaction time or milder conditions under

268
ZHI-PING LIN et al.
ultrasound irradiation. The preparation of 1,3,5-triaryl-2-pyrazolines has been reported13 in
2007, but the reaction was occurred at high temperature. In this paper we wish to report an
efficient and practical procedure for the synthesis of 1,3,5-triaryl-2-pyrazolines with
chalcones and phenylhydrazine in acetic acid under ultrasound irradiation at room
temperature (Scheme 1). In this protocol, acetic acid is the reaction solvent and also is the
catalyst.
Ar1
Ar2
Ar2
Ar1
CH3COOH
Ultr und,r.r.tt.
+
PhNHNH2
O
N
N
u
a
.
s
s
o
.
Ph
3
1
2
Scheme 1. Synthesis of 1,3,5-triaryl-2-pyrazolines under ultrasound irradiation
Experimental
1
Liquid substrates were distilled prior to use. Melting points were uncorrected. H NMR
spectra were recorded on a Bruker AVANCE 600 (600 MHz) spectrometer using TMS as the
internal standard and CDCl3 as solvent. Elemental analyses were measured on a HERAEUS
(CHNO, Rapid) analyzer. Sonication was performed in Shanghai BUG40-06 or BUG25-06
ultrasonic cleaner (with a frequency of 25 kHz, 40 kHz, 59 kHz and a nominal power 250 W).
Typical procedure for the preparation of 1,3,5-triaryl-2-pyrazolines
The chalcones was prepared by the reported method14. Chalcones (1, 2 mmol) and
phenylhydrazine (2, 6 mmol) were dissolved in acetic acid (6 mL) in a 50 mL conical flask.
The mixture was irradiated in the water bath of an ultrasonic cleaner for the period as
indicated in Table 2. The reaction mixture was poured into crushed ice. The precipitate was
separated by filtration, washed with water, and crystallized from ethanol to obtain the
1
1,3,5-triaryl-2-pyrazolines. The authenticity of compounds were established by their H
NMR, elemental analysis data and melting point.
1
3a H NMR (DMSO): δ 3.13 (dd, J=7.2, 17.2 Hz, 1H), 3.82 (dd, J=12.4, 16.8 Hz, 1H),
5.26 (dd, J=7.2, 12 Hz, 1H) 6.80-7.75 (m, 14H) ppm. Anal. calcd. for C21H18N2: C 84.56, H
6.04, N 9.39; found C 84.60, H 6.14, N 9.37.
1
3b: H NMR (DMSO): δ 3.14 (dd, J=7.2, 17.2 Hz, 1H), 3.80 (s, 3H, OCH3), 3.84
(dd, J=12.4, 16.8 Hz, 1H), 5.26 (dd, J=7.2, 12 Hz, 1H) 6.80-7.75 (m, 14H) ppm. Anal. calcd.
for C22H20N2O: C 80.48, H 6.09, N 8.54; found C 80.50, H 6.04, N 8.49.
1
3c: H NMR (DMSO): δ 2.38 (s, 3H, CH3), 3.15 (dd, J=7.2, 17.2 Hz, 1H), 3.85
(dd, J=12.4, 17.2 Hz, 1H), 5.27 (dd, J=6.8, 12 Hz, 1H) 6.77-7.75 (m, 14H) ppm. Anal. calcd.
for C22H20N2: C 84.62, H 6.41, N 8.97; found C 84.61, H 6.43, N 9.00.
3d: 1H NMR (DMSO): δ 3.09 (dd, J=6.8, 17.2 Hz, 1H), 3.40 (dd, J=12.4, 17.2 Hz, 1H),
5.68 (dd, J=6.8, 12.4 Hz, 1H) 6.85-7.76 (m, 14H) ppm. Anal. calcd. for C21H17N2Cl: C
75.90, H 5.12, N 8.43; found C 75.83, H 5.23, N 8.45.
3e: 1H NMR (DMSO): δ 3.08 (dd, J=6.8, 17.2 Hz, 1H), 3.40 (dd, J=12.4, 17.2 Hz, 1H),
5.68 (dd, J=6.8, 12.4 Hz, 1H) 6.83-7.77 (m, 14H) ppm. Anal. calcd. for C21H17N2Cl: C
75.90, H 5.12, N 8.43; found C 75.93, H 5.13, N 8.45.
3f: 1H NMR (DMSO): δ 3.08 (dd, J=6.8, 17.2 Hz, 1H), 3.40 (dd, J=12.4, 17.2 Hz, 1H),
5.68 (dd, J=6.8, 12.4 Hz, 1H) 6.83-7.77 (m, 14H) ppm. Anal. calcd. for C21H17N2Cl: C
75.90, H 5.12, N 8.43; found C 75.93, H 5.14, N 8.44.

A Convenient and Efficient Protocol for the Synthesis
269
3g: 1H NMR (DMSO): δ 3.06 (dd, J=6.8, 17.1 Hz, 1H), 3.37 (dd, J=12.4, 17.2 Hz, 1H),
5.65 (dd, J=6.8, 12.4 Hz, 1H) 6.81-7.76 (m, 14H) ppm. Anal. calcd. for C21H17N2: C 85.85,
H 5.72, N 9.43; found C 85.81, H 5.73, N 9.44.
1
3h: H NMR (DMSO): δ 3.01 (dd, J=7.8, 16.8 Hz, 1H), 3.78 (s, 3H, OCH3), 3.82
(dd, J=12.4, 16.8 Hz, 1H), 3.84 (s, 3H, OCH3), 5.26 (dd, J=7.2, 12 Hz, 1H) 6.80-7.75 (m, 13H)
ppm. Anal. calcd. for C23H22N2O2: C 77.09, H 6.18, N 7.81; found C 76.69, H 6.14, N 7.70.
1
3i: H NMR (DMSO): δ 3.15 (dd, J=7.2, 17.2 Hz, 1H), 3.80 (s, 3H, OCH3), 3.84
(dd, J=12.4, 16.8 Hz, 1H), 5.28 (dd, J=7.2, 12 Hz, 1H) 6.80-7.75 (m, 13H) ppm. Anal. calcd.
for C22H19N2OCl: C 72.93, H 5.25, N 7.73; found C 71.50, H 5.34, N 7.49.
3j: 1H NMR (DMSO): δ 3.14 (dd, J=17.2, 17.2 Hz, 1H), 3.84 (dd, J=12.4, 17.2 Hz, 1H),
5.32 (dd, J=7.6, 12.4 Hz, 1H) 6.80-7.68 (m, 14H) ppm. Anal. calcd. for C21H17N2: C 84.85,
H 5.72, N 9.43; found C 84.87, H 5.74, N 9.46.
Results and Discussion
The effect of the reaction conditions on the reaction of chalcones and phenylhydrazine under
ultrasound irradiation was summarized in Table 1. When the molar ratio of chalcones (1):
phenylhydrazine (2) was 1:1, the yield of 1,3,5-triphenyl-2-pyrazoline was obtained in
88.1% yield (Table 1, Entry a). By increasing the molar ratio to 1:1.5, 1:2, and 1:3 the yields
increased to 90.0, 93.5 and 95.6% respectively (Table 1, Entry b, c, d). The results showed
that changing the molar ratio of 1:2 had a significant effect on the yield and the optimum
molar ratio of chalcone: phenylhudrazine was 1:3. In the absence of ultrasound, the yield of
1,3,5-triphenyl-2-pyrazoline was only 77.0% (Entry l) by stirring at room temperature within
2 h. The data of entry b, c, d, h and j in Table 2 also verify the effect of ultrasound. It is
apparent that the reaction can be finished in a shorter time to give better yield under
ultrasound.
Table 1. Effect of reaction condition on synthesis of 1,3,5-triphenyl-2-pyrazoline within 2 h
under ultrasound
Entry
Molar ratio of 1:2
1:1.0
1:1.5
Frequency, kHz
solvent
HAc
HAc
Isolated yield, %
a
b
c
d
e
f
25
25
25
25
40
59
25
25
25
59
25
Stira
88.1
90.0
93.5
95.6
94.6
92.6
89.1
55.0
23.0
trace
0
1:2.0
1:3.0
HAc
HAc
1:3.0
1:3.0
HAc
HAc
g
h
i
1:3.0
1:3.0
EtOH
HAc:H2O=3:1
HAc:H2O=2:2
HAc:H2O=1:3
H2O
1:3.0
1:3.0
j
k
l
1:3.0
1:3.0
HAc
77.0
aStirred without ultrasound irradiation
When the frequency was 25 kHz, the reaction gave the desired product in 95.6% yield
within 2 h min (Entry d). Under 40 kHz and 59 kHz ultrasound irradiation, the
1,3,5-triphenyl-2-pyrazoline was obtained with 94.6% and 92.6% yield respectively
(Entry e and f), thus indicating that different frequency of ultrasound irradiation had no
significant effect on the yield of 1,3,5-triphenyl-2-pyrazoline.

270
ZHI-PING LIN et al.
We also carried out the reaction of chalcones and phenylhydrazine in acetic acid using
different solvents under ultrasound. The results are listed in Table 1. The reaction in acetic
acid proceeded smoothly under ultrasound irradiation, while not so efficient in the solvent
including water. So the study continued to be done using acetic acid. And the most important
in our protocol, no other catalyst need to add during the reaction. The acetic acid is the
reaction solvent and also is the catalyst.
From the above results, the optimum reaction conditions were chosen; chalcone
(1), 2 mmol, phenylhydrazine (2), 6 mmol and acetic acid 6 mL. Under this reaction system,
a series of experiments for synthesis of 1,3,5-triaryl-2-pyrazolines under 25 kHz ultrasound
irradiation were performed. The results are summarized in Table 2.
Table 2. Synthesis of 1,3,5-triaryl-2-pyrazolines in acetic acid under ultrasounics at room
temparature
Entry
Ar1
Ar2
C6H5
Time, min Yield, % m.p.Found(Lit.) oC [Ref.]
a
C6H5
C6H5
120
110
95.6
99.0
85.5a
99.0
80.1a
94.9
79.8a
87.8
84.9
18.3
97.9
134-135(134-135)[6]
110-111(110-112)[13]
-
b
4-CH3OC6H4
c
C6H5
C6H5
4-CH3C6H4
4-ClC6H4
90
127-129(128-130)[13]
-
d
120
134-135(135-136)[13]
-
e
f
C6H5
C6H5
C6H5
3-ClC6H4
2-ClC6H4
3-BrC6H4
100
100
180
60
134-135(134-136)[13]
134-135(135-136)[13]
141-142(141-143)[13]
139-141(139-140)[15]
g
h
4-CH3OC6H4 4-CH3OC6H4
81.3a
95.5
89.5
-
i
j
4-ClC6H4
4-ClC6H4
4-CH3OC6H4
C6H5
60
90
158-159(160-161)[16]
142-144(143-145)[13]
75.9a
-
-
k
C6H5
4-NO2C6H4
180
trace
aThe reaction was occurred without ultrasound
From the Table 2 data, it seems that either electron-donating substituents or electron-
withdrawing substituents in the benzene ring have no significant effects on the yields in this
system. 1,3-Diphenyl-5-(4-methylphenyl)-2-pyrazoline and 1,3-diphenyl-5-(4-chlorophenyl)
-2-pyrazoline can obtain in 88% and 86% yield as per literature report, but it is higher to
99.0% and 94.9% in present system at room temperature. Moreover, acetic acid both is the
reaction solvent, and is the catalyst.
In conclusion, we have found an efficient and practical procedure for the synthesis of
some 1,3,5-triaryl-2-pyrazolines via the condensation of chalcones and phenylhydrazine
under ultrasound irradiation at room temperature.
Acknowledgment
The project was supported by Natural Science Foundation of Hebei Province (B2006000969),
China.

A Convenient and Efficient Protocol for the Synthesis
271
References
1.
2.
3.
4.
Patel V M and Desai K R, Arkivoc, 2004, (i), 123.
Chen Y, Lam Y L and Lai Y H, Org Lett., 2003, 5, 1067.
Parmar S S, Pandey B R, Dwivedi C and Harbinson R D, J Pharm Sci., 1974, 63, 1152.
Soni N, Pande K, Kalsi R, Gupta T K, Parmar S S and Barthwal J P, Res Commun
Chem Pathol Pharm., 1987, 56(1), 129-132.
5.
6.
Turan-Zitouni G, Chevallet P, Kilic F S and Erol K, Eur J Med Chem., 2000, 35(6),
635-641.
Rajendra Y P, Lakshmana R A, Prasoona K, Murali K and Ravi K P, Bioorg Med
Chem Lett., 2005, 15, 5030-5034.
Salgado V L, Pesti Sci., 1990, 28, 389.
7.
8.
9.
Franck-Neumann M and Miesch M, Tetrahedron Lett, 1982, 23, 1409.
Jin M, Lu Ran, Chuai X H, Zhang Y H and Zhao Y Y, Chem J Chin Univ., 2002, 23, 466.
10. Zhu W H and Tian H, Prog Chem., 2002, 14, 18.
11. Zhang X H, Wu S K, Gao Z Q, Li Z S and Li S T, Acta Chimica Sinaca, 2000, 58, 293.
12. Levai A, ARKIVOC, 2005, (ix), 344.
13. Li J T, Zhang X H and Lin Z P, Beilstein J Org Chem., 2007, 3, 13.
14. Li J T, Yang W Z, Wang S X, Li S H and Li T S, Ultrason Sonochem., 2002, 9, 237-239.
15. Ando W, Sato R, Yamashita M, Akasaka T and Miyazaki H, J Org Chem., 1983,
48, 542.
16. Kidwai M, Kukreja S and Thakur R, Lett Org Chem., 2006, 3, 135.

International Journal of
Advances in
Organic Chemistry
International
International Journal of
International Journal of
Photoenergy
Medicinal Chemistry
Analytical Chemistry
Physical Chemistry
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Volume 2014
http://www.hindawi.com
Volume 2014
http://www.hindawi.com
Volume 2014
Volume 2014
International Journal of
Carbohydrate
Chemistry
Journal of
Quantum Chemistry
Hindawi Publishing Corporation
Hindawi Publishing Corporation
http://www.hindawi.com
http://www.hindawi.com
Volume 2014
Volume 2014
Submit your manuscripts at
http://www.hindawi.com
Journal of
The Scientific
Analytical Methods
in Chemistry
World Journal
Hindawi Publishing Corporation
Hindawi Publishing Corporation
http://www.hindawi.com
http://www.hindawi.com
Volume 2014
Volume 2014
International Journal of
Journal of
Journal of
International Journal of
Bioinorganic Chemistry
Spectroscopy
Inorganic Chemistry
Electrochemistry
Applied Chemistry
and Applications
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
Hindawi Publishing Corporation
Hindawi Publishing Corporation
Hindawi Publishing Corporation
Volume 2014
http://www.hindawi.com
Volume 2014
http://www.hindawi.com
Volume 2014
http://www.hindawi.com
Volume 2014
http://www.hindawi.com
Volume 2014
Journal of
Journal of
International Journal of
Chromatography
Journal of
Theoretical Chemistry
Catalysts
Research International
Chemistry
Spectroscopy
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Volume 2014
Volume 2014
Volume 2014
Volume 2014