Facile Microwave-assisted Synthesis of 1,3,5-Trisubstituted Pyrazoline Derivatives Incorporating Sulfonyl Moiety

Article abstract of DOI:10.1002/jccs.201500385

We developed an environmentally benign, convenient microwave-assisted process for the construction of 1,3,5-trisubstitued pyrazolines (10a～10f, 11a～11f, 12a～12f, 13a～13f). Chalcones, as the key intermedi- ates, were obtained by the condensation of each of appropriately substituted aromatic aldehydes (1～4) with 4-substituted acetophenones (5a～5f) via a Claisen-Schmidt reaction under the action of microwave irradiation. Cyclization of the chalcones (6a～6f, 7a～7f, 8a～8f, 9a～9f) with p-toluene sulfonhydrazide af- forded 1,3,5-trisubstitued pyrazoline derivatives using microwave-assisted process in 25 min and 140 watt power in glycol. The structures of targeted compounds were established by IR, ¹H NMR, MS and ele- mental analysis. The results indicate that microwave-assisted synthetic process presents advantages in terms of enhancement in rate, decrease in reaction time, clean reaction and convenient operation.

Full text of DOI:10.1002/jccs.201500385

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Facile Microwave-assisted Synthesis of 1,3,5-Trisubstituted Pyrazoline Derivatives
Incorporating Sulfonyl Moiety
Fei Liu,a Jin-Feng Yang,a* Hong Liu,b Wen-Zhen Weia and Yan-Mei Maa
aKey Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan/College of Chemistry and
Chemical Engineering, Shihezi University, Shihezi, 832000, P.R. China
bCollege of Science, Shihezi University, Shehezi, 832000, P.R. China
(Received: Sept. 18, 2015; Accepted: Dec. 21, 2015; Published Online: Jan. 26, 2016; DOI: 10.1002/jccs.201500385)
We developed an environmentally benign, convenient microwave-assisted process for the construction of
1, 3, 5-trisubstitued pyrazolines (10a~10f, 11a~11f, 12a~12f, 13a~13f). Chalcones, as the key intermedi-
ates, were obtained by the condensation of each of appropriately substituted aromatic aldehydes (1~4)
with 4-substituted acetophenones (5a~5f) via a Claisen-Schmidt reaction under the action of microwave
irradiation. Cyclization of the chalcones (6a~6f, 7a~7f, 8a~8f, 9a~9f) with p-toluene sulfonhydrazide af-
forded 1, 3, 5-trisubstitued pyrazoline derivatives using microwave-assisted process in 25 min and 140
watt power in glycol. The structures of targeted compounds were established by IR, 1H NMR, MS and ele-
mental analysis. The results indicate that microwave-assisted synthetic process presents advantages in
terms of enhancement in rate, decrease in reaction time, clean reaction and convenient operation.
Keywords: Microwave irradiation; Chalcone; Pyrazoline; Synthesis.
INTRODUCTION
Nitrogen containing heterocyclic compounds are
search of heterocycle-based pyrazoline is supposed to be
continued.
core structure of numerous biological active compounds1
and receive considerable attention due to their wide appli-
cations. Azole moiety is a prevalent scaffold in a number of
natural occurring and synthetic molecules with attractive
biological activities.2 Oxadiazoline, pyrazole and pyrazo-
line derivatives are in general well-known five-membered
containing heterocyclic compounds.3 Among these aza
containing heterocyclic compounds, pyrazole derivatives
play a crucial role in the development of the theory in
heterocyclic chemistry. Pyrazole motif and its derivatives
have been the subject of great interest for their pharmaceu-
tical activities such as anti-inflammatory, antimicrobial,
antiviral, anxiolytic, antioxidant and anticonvulsant.4-9 In
particular, trisubstitued pyrazolines play an important role
in biological evaluation.10-12 Furthermore, sulfonyl group
within cyclic compounds, especially at a strategic positon,
has become an important aspect to be studied in pharma-
ceutical research.13 Not only that, but pyrazoline deriva-
tives have been used as whitening or brightening reagents
for fluorescent chemosensors for recognition of transition
metal ions and electroluminescence fields. Some pyrazo-
line-based fluorescent probes for metal ions, for example
Zn2+, Cu2+ and Hg2+ have been reported.14-16 Due to their
outstanding properties as mentioned above, the further re-
Many methods have been described for the prepara-
tion of pyrazoline derivetives.17-19 Chalcones, either natu-
ral or synthetic, are known as starting materials or valuable
intermediates for synthesizing a series of heterocyclic com-
pounds.2,20 However, traditional methods of synthesis of
pyrazole derivetives suffer from disadvantages, such as
long reaction time, low pratical yield and inconvenient
handling. Longtime reaction demands much more energy
and driving force. Thus, the introduction of efficient and
eco-friencdly new methods based on green methodology is
still in great demand. As a nonconventional heating source,
microwave (MW) technology is progressively developed,
and gradually applied in organic synthesis.21,22 Compared
to conventional heating, microwave energy penetrates and
produces a volumetrically distributed heat source, and heat
is generated throughout the material and leads to faster
heating rate and improved kinetics.23 Hence, reactions that
require hours or even days by conventional heating can of-
ten be accomplished in seconds or minutes by microwave
irradiation. So far, microwave-assisted synthetic strategies
to obtain trisubstituted pyrazolines are still scarce.
Microwave-assisted synthesis is an experimental
technique with clean and environmentally benign. As our
interest in utilizing green chemistry tools to synthesize or-
* Corresponding author. Tel: 18999737501; Email: yangjinfeng@shzu.edu.cn
254
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J. Chin. Chem. Soc. 2016, 63, 254-260

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Facile Microwave-assisted Synthesis of 1,3,5-trisubstituted Pyrazoline Derivatives
ganic compounds in technologies and concepts to facilitate
a more rapid synthesis, we carry out a facile microwave-as-
sisted synthesis of 1, 3, 5-trisubstituted pyrazoline deriva-
tives. Consequently, in this paper, chalcones (6a~6f, 7a~7f,
8a~8f, 9a~9f) are synthesized as the key intermediates us-
ing microwaves activation. Furthermore, 1, 3, 5-trisub-
stituted pyrazolines (10a~10f, 11a~11f, 12a~12f, 13a~
13f) are synthesized conveniently via cyclization of formed
chalcone with sulfonyl hydrazine using microwave energy,
with ice glacial acetic acid as catalyst, in glycol. The syn-
thetic route of target compounds are shown in Scheme 1.
The method for forming trisubstituted pyrazolines under
microwave irradiation offers several advantages including
faster heating rate and shorter reaction times, while the
conventional method endures a long process and inconve-
nient work-up.
geted compounds is carried out with different time using mi-
crowave energy (Table 4). It is found that the highest yield
could be accessible when the reaction mixture (mole ratio:
1:1.1) is intermittently irradiated for 25 min and 140 watt
power in glycol. In contrast, compounds 10a~10f with mi-
crowave irradiation, not only but also are synthesized by
conventional heating (Table 5). It is found that the method
of microwave irradiation have advantages of higher yield
rate and shorter reaction times. Finally, the same protocol
(mole ratio of material, watt and run time) is kept fixed for
Table 1. Loss factor value (tan d) of solvents estimated at 20 °C
Solvents
Frequency
tan d
b.p. (°C)
Glycol
Ethanol
Methanol
2.45 GHz[a]
2.45 GHz
2.45 GHz
1.350
0.941
0.659
197.3
78.5
64.7
[a] 2.45 GHz is the operating frequency of commercial
microwave ovens.
RESULTS AND DISCUSSION
There is a growing interest to improve the energetic ef-
ficiency of the synthesis of 1,3,5-trisubstituted pyrazolines.
With compound 10a in hand, the ring-closure reaction is op-
timized using microwave procedure. Firstly, methanol and
ethanol are used as the reaction solvent instead of glycol, but
they result in incomplete reaction even the solvent boils
away. It could be concluded that glycol is very effective be-
cause of its good character with both high tan d values and
high boiling point. The ability of a given substance to con-
vert electromagnetic energy into heat, is determined by the
loss tangent factor (tan d). Substances with high tan d values
are well-suited canditates for microwave applications24 (Ta-
ble 1). The mode of microwave irradiation is then studied
(Table 2). It is found that the power irradiation (140 W) is
adopted. The mole ratio of material is also one of important
parameters, as illustrated in Table 3. The synthesis of tar-
Table 2. Yields of compound 10a under different watt
Entry
Power/w
Yield/%
1
2
3
4
5
100
120
140
160
180
62
71
82
72
66
Table 3. Yields of compound 10a under different molar ratio of
material
Entry
Molar ratio
Yield/%
1
2
3
4
5
1:0.5
1:0.7
1:1.1
1:1.3
1:1.5
35
48
79
79
80
Synthesis of 1,3,5-trisubstituted pyrazoline
Scheme 1
J. Chin. Chem. Soc. 2016, 63, 254-260
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Article
Liu et al.
Table 4. Effect of microwave irradiation time on the yields of
10a
4.8 Hz). The signal at d 6.74-7.91 ppm was assigned to H of
benzene ring. The methyl of benzene showed single signal
at d 2.23 ppm. In addition, the single signal at d 3.69 ppm
was due to methoxy group proton of compounds, and the
single signals of OH proton showed at d 9.35-9.68 ppm.
The single signal at 3.03 ppm was due to -N(CH3)2 proton
of compounds (10b~13b). The data of 1H NMR spectra of
target compounds are listed in Table 8.
Entry
Time/min
Yield/%
1
2
3
4
5
6
10
15
20
25
30
35
34
54
65
80
80
78
The MS (ESI) spectra displayed that all synthesized
compounds had quasi-molecular on peaks; most of which
were the base peaks. The elemental analysis date and MS
data of target compounds are listed in Table 7.
Table 5. Effect of different energy source on the yields of
10a~10f
Conventional heat energy
Microwave irradiation
Compd.
Time/min
Yield/%
Time/min
Yield/%
EXPERIMENTAL
10a
10b
10c
10d
10e
10f
290
270
300
310
280
290
64
56
65
60
62
58
25
21
23
25
22
24
79
78
75
76
75
77
General: Unless otherwise indicated, all common reagents
were used as obtained from commercial suppliers without further
purification. All melting points were measured using WC-1 micro-
scopic melting point apparatus and are uncorrected. The IR spectra
were recorded in KBr pellets on a Brucker Equinox-55 FT-IR appa-
ratus. The 1HNMR spectra were recorded on an INOVA-400 (using
TMS as internal standard, CDCl3 as solvent). Mass spectra were re-
corded on an HP 1100 LC-MS (ESI). Elemental analyses were per-
formed on Perkin-Elmer 2400 CHN analyzer. Microwave reactor is
modified by EM-202MS1 700W household microwave oven of the
SANYO brand, output power continuously adjustable, and fre-
quency of 2450 MHz. All reagents were commercial products of
analytical grade and can be used directly without purification ex-
cept where they are especially noted.
the preparation for compounds 10~13.
The positions of IR band provide significant indica-
tion for the formation of compounds (10~13). Firstly, there
is no sharp peak at 1656 cm-1 attributing to C=O. Sen-
condly, two middle sharp peaks both 1125-1145 cm-1 and
1338-1304 cm-1 is assigned to O=S=O stretching which
shifted to the low wave number as to conjugation of ben-
zen. Thirdly, the absorption bands at 1597-1580 cm-1 are at-
tributed to the C=N stretching vibrations in pyrazole ring,
which also confirme the formation of desired pyrazole ring
in the compounds (10~13). And, a weak band appeared at
3000~3100 cm-1 is assigned to C-H stretching vibration on
the benzene ring. The strong absorption bands at 1600,
1550, 1500 cm-1 are attributed to the skeleton vibration of
benzene. In addition, 9f~13f show a broad peak at 3433~
3350 cm-1 correspongding to OH. The data of the IR spec-
tra of the targeted compounds are listed in Table 8.
Synthesis of p-toluene Sulfonyl Hydrazine: 4-methyl
benzene sulfonyl chloride (1.0 mmol) and hydrazine hydrate (1.7
mL) in benzene (8 mL) were refluxed at the temperature of 60-70
°C for 2 h, the needle crystal appeared after cooling and standing,
the solution was filtered to afford crude product, which was
recrystallized from ethanol as needle crystals. The yield is 65%,
m.p. 106~107 °C.
Synthesis of chalcone derivatives (6~9)
Compounds (6a~6d, 8a~8d, 9a~9d) were prepared
according to the method A.
Further evidence for the formation of the target com-
pounds is obtained by 1H NMR spectroscopy. The H1 NMR
spectra of (10~13) show three signals as doublet of dou-
blet, each of one proton intensity. The first at d 3.41~3.53,
the second at d 3.55~4.06 are attributed to two protons at
position 4, and the third at d 5.75~6.08 is corresponding to
the proton at position 5 in pyrazoline. Two protons cou-
pling between each other at position 4, have higer J value (J
= 17.6 Hz). The proton at position 5 coupling two protons
at position 4 respectively, has lower J value (J = 12.4 Hz,
Compounds (6f~9f, 7a~7e) were prepared according to
the method B.
Method A: Aromatic aldehydes (5a~5e, 1.0 mmol) was in
10 mL of methol. Aromatic ketone (1, 3, 4, 1.0 mmol) was added
dissolved in 10 mL methol. The mixture was kept on a magnetic
stirrer and slowly a stream of sodium methoxide solution (10 mL)
was added. And then, the above prepared mixture in the open ves-
sel was irradiated under the microwave condition for 25 min. The
progess of the reaction was monitored by TLC whose solvent
256
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Facile Microwave-assisted Synthesis of 1,3,5-trisubstituted Pyrazoline Derivatives
system was acetone:petroleum ether(1:3 v/v). The content was
poured into crushed ice and thoroughly acidified to be neutral.
The completion (6a~6d, 8a~8d, 9a~9d) was isolated and crystal-
lized from ethanol (95%).
tives (10a~10f, 11a~11f, 12a~12f, 13a~13f): p-toluene sulfonyl
hydrazine reagent (5.0 mmol) was added dropwise to a stirred so-
lution of each of Chalcones (6~9, 5.5 mmol) in glycol (20 mL),
and then the catalytic amount of glacial acetic acid was stirred for
a few minutes. The mixture in the open vessel was then intermit-
tently irradiated in a microwave at 140 W for 25 min. The progess
of the reaction was monitored by TLC whose solvent system was
acetone: petroleum ether (1:3 v/v). The product was poured into
ice-cold water. The precipitate of pyrazoline (10~13) was ob-
tained which was filtered and dried. The product was crystallized
from 95% ethanol. The elemental analysis and MS data of com-
Method B: Amixture of 4-hydroxyl acetophenone 2 (1.0 m
mol) and 4-hydroxy-3-methoxy-benzaldehyde (5f, 1.6 mmol)
were irradiated under the microwave condition for 25 min in gly-
col using the catalyst of boric acid. The progess of the reaction
was monitored by TLC whose solvent system was acetone: petro-
leum ether (1:3 v/v). The product was purified by the flash chro-
matography on silica gel.
1
The physical data of compounds (6~9) are given in Table 6.
Synthesis of 1, 3, 5-trisubstituted Pyrazolines Deriva-
pounds are given in Table 7. The data of the IR spectra and H
NMR spectra are listed in Table 8.
Table 6. Physical data of compounds (6~9)
Compd.
Formula
m.p./°C
Compd.
Formula
m.p./°C
6a
6b
6c
6d
6e
6f
7a
7b
7c
7d
7e
7f
C15H12O
C17H17NO
C15H11ClO
54~55 (lit17: 54~55)
108~109
8a
8b
8c
8d
8e
8f
9a
9b
9c
9d
9e
9f
C15H11BrO
103~104
C17H16BrNO 133~135 (lit27: 133~135)
50~52 (lit26: 49~50)
C15H10BrClO
C15H10BrClO
C15H9BrCl2O
C16H13BrO3
C16H14O2
88~91
164~166
102~103
C15H11ClO 112~113 (lit26: 109~110)
C15H10Cl2O
C16H14O3
72~73
> 250
198~200
C15H12O2 178~179 (lit2: 180~182)
105~107 (lit28: 105~106)
C17H17NO2
C15H11ClO2
C15H11ClO2
C15H10Cl2O2
C16H14O4
200~202
179~180
147~148
71~72
C8H19NO2 125~158 (lit27: 125~126)
C16H13ClO2
C16H13ClO2
C16H12Cl2O2
C17H16O4
91~92
129~130
136~137
165~168
216~218
Table 7. Physical data, the elemental analysis and MS data of compounds (10~13)
Elemental analysis(calcd.)%
Compd.
Formula
m.p./°C Yield/%
MS m/z (%)
C
H
N
10a
10b
10c
10d
10e
10f
11a
11b
11c
11d
11e
11f
12a
12b
12c
12d
12e
12f
13a
13b
13c
13d
13e
13f
C22H20N2O2S
C24H25N3O2S
C22H19ClN2O2S
C22H19ClN2O2S
C22H18Cl2N2O2S
C23H22N2O4S
175~176
127~128
124~125
132~133
131~132
121~122
155~156
173~175
153~154
148~149
168~169
173~174
166~167
183~184
79
78
75
76
75
77
79
71
70
68
66
69
82
65
65
68
72
67
80
78
78
79
74
67
70.19 (70.24) 5.35 (5.31) 7.44 (7.41) 377 ([M+H]+, 100)
68.71 (68.71) 6.02 (6.02) 10.02 (10.02) 420 ([M+H]+, 100)
64.30 (64.32) 4.66 (4.63) 6.82 (6.81) 411 ([M+H]+, 100)
64.30 (64.29) 4.66 (4.64) 6.82 (6.85) 411 ([M+H]+, 100)
59.33 (59.32) 4.07 (4.02) 6.29 (6.30) 446 ([M+H]+, 100)
65.38 (65.34) 5.25 (5.27) 6.63 (6.64) 423 ([M+H]+, 100)
67.33 (67.38) 5.14 (5.12) 7.14 (7.11) 393 ([M+H]+, 100)
66.18 (66.28) 5.79 (5.78) 9.65 (9.66) 436 ([M+H]+, 100)
61.89 (61.88) 4.49 (4.51) 6.56 (6.59) 427 ([M+H]+, 100)
61.89 (61.92) 4.49 (4.43) 6.56 (6.60) 427 ([M+H]+, 100)
57.27 (57.22) 3.93 (3.92) 6.07 (6.10) 462 ([M+H]+, 100)
63.00 (63.02) 5.06 (5.02) 6.39 (6.40) 439 ([M+H]+, 100)
58.03 (58.05) 4.21 (4.17) 6.15 (6.13) 456 ([M+H]+, 100)
57.83 (57.81) 4.85 (4.82) 8.43 (8.42) 499 ([M+H]+, 100)
53.95 (53.91) 3.70 (3.74) 5.72 (5.74) 490 ([M+H]+, 100)
53.95 (53.95) 3.70 (3.71) 5.72 (5.73) 490 ([M+H]+, 100)
50.40 (50.40) 3.27 (3.22) 5.34 (5.31) 525 ([M+H]+, 100)
55.10 (55.14) 4.22 (4.27) 5.59 (5.54) 502 ([M+H]+, 100)
67.96 (67.98) 5.46 (5.42) 6.89 (6.86) 407 ([M+H]+, 100)
66.79 (66.71) 6.05 (6.02) 9.35 (9.32) 450 ([M+H]+, 100)
62.65 (62.61) 4.80 (4.73) 6.35 (6.40) 441 ([M+H]+, 100)
62.65 (62.62) 4.80 (4.72) 6.35 (6.40) 441 ([M+H]+, 100)
58.11 (58.12) 4.24 (4.22) 5.89 (5.90) 477 ([M+H]+, 100)
63.70 (63.62) 5.35 (5.32) 6.19 (6.20) 453 ([M+H]+, 100)
C22H20N2O3S
C24H25N3O3S
C22H19ClN2O3S
C22H19ClN2O3S
C22H18Cl2N2O3S
C23H22N2O5S
C22H19BrN2O2S
C24H24BrN3O2S
C22H18BrClN2O2S 134~135
C22H18BrClN2O2S 156~157
C22H17BrCl2N2O2S 124~125
C23H21BrN2O4S
C23H22N2O3S
162~163
94~95
C25H27N3O3S
158~159
148~149
163~165
115~116
195~197
C23H21ClN2O3S
C23H21ClN2O3S
C23H20Cl2N2O3S
C24H24N2O5S
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Table 8. IR, 1H NMR data of compounds (10~13)
Compd.
IR (KBr) n/cm-1
1H NMR (CDCl3, 400 MHz) d
10a
3057 (w, Ar-H), 1591 (C=N), 1599, 1544, 1495,
1435 (s, Ar-C), 1309, 1125 (m, O=S=O)
7.31~7.91 (m, 14H, Ar-H), 5.96 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.55 (dd, 1H, J =12.4, 17.4 Hz, Pyrazoline-H), 3.51 (dd, J = 4.8 Hz,
J = 17.4 Hz, 1H, Pyrazoline-H), 2.25 (s, 3H, -CH3).
10b
10c
10d
10e
10f
3054 (w, Ar-H), 1592 (C=N), 1603, 1560, 1493,
1435 (s, Ar-C), 1329, 1140 (m, O=S=O)
6.74~7.76 (m, 13H, Ar-H), 5.86 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.85 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.52 (dd, J = 4.8 Hz,
J = 17.4 Hz, 1H, Pyrazoline-H), 3.04 (s, 6H, NCH3), 2.23 (s, 3H, -CH3).
7.26~7.75 (m, 13H, Ar-H), 6.08 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.96 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.62 (dd, J = 4.8 Hz,
J = 17.4 Hz, 1H, Pyrazoline-H), 2.19 (s, -3H, -CH3).
7.24~7.87 (m, 13H, Ar-H), 5.76 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.75 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.50 (dd, J = 4.8 Hz,
J = 17.4 Hz, 1H, Pyrazoline-H), 2.17(s, 3H, -CH3).
3059 (w, Ar-H), 1594 (C=N), 1617, 1540, 1497,
1437 (s, Ar-C), 1322, 1140 (m, O=S=O)
3058 (w, Ar-H), 1593 (C=N), 1615, 1578, 1498,
1468 (s, Ar-C), 1319, 1135 (m, O=S=O)
3057 (w, Ar-H), 1594 (C=N), 1613, 1548, 1498,
1457 (s, Ar-C), 1339, 1122 (m, O=S=O)
7.26~7.78 (m, 12H, Ar-H), 5.77 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.65 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.43 (dd, J = 4.8 Hz,
J = 17.4 Hz, 1H, Pyrazoline-H), 2.27 (s, 3H, -CH3).
3370 (s, O-H), 3067 (w, Ar-H), 1597 (C=N),
9.55 (s, 1H, -OH), 6.92~7.76 (m, 12H, Ar-H), 5.98 (dd, J = 4.8, 12.4 Hz,
1616, 1577, 1489, 1455 (s, Ar-C), 1340, 1125 (m, 1H, Pyrazoline-H), 3.84 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.66
O=S=O)
(s, 3H, -OCH3), 3.51 (dd, J = 4.8 Hz, J = 17.4 Hz, 1H, Pyrazoline-H),
2.23 (s, 3H, -CH3).
11a
11b
3358 (s, O-H), 3057 (w,Ar-H), 1598 (C=N), 1603, 9.40 (s, 1H, -OH), 6.73~7.75 (m, 13H, Ar-H), 5.82 (dd, J = 4.8, 12.4 Hz,
1548, 1493, 1435 (s, Ar-C), 1329, 1126 (m,
O=S=O)
1H, Pyrazoline-H), 3.84 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.61
(dd, J = 4.8 Hz, J = 17.4 Hz, 1H, Pyrazoline-H), 2.17 (s, 3H, -CH3).
9.35 (s, 1H, -OH), 6.78~7.72 (m, 12H, Ar-H), 5.68 (dd, J = 4.8, 12.4 Hz,
3355 (s, O-H), 3057 (w, Ar-H), 1592 (C=N),
1608, 1547, 1494, 1435 (s, Ar-C), 1334, 1145 (m, 1H, Pyrazoline-H), 3.84 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.51
O=S=O)
(dd, J = 4.8 Hz, J = 17.4 Hz, 1H, Pyrazoline-H), 3.14 (s, 6H, NCH3),
2.17 (s, 3H, -CH3).
11c
11d
11e
11f
3357 (s, O-H), 3057 (w, Ar-H), 1594 (C=N),
9.41 (s, 1H, -OH), 6.75~7.75 (m, 12H, Ar-H), 5.98 (dd, J = 4.8, 12.4 Hz,
1614, 1568, 1498, 1447 (s, Ar-C), 1339, 1125 (m, 1H, Pyrazoline-H), 3.96 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.55
O=S=O) (dd, J = 4.8 Hz, J = 17.4 Hz, 1H, Pyrazoline-H), 2.28 (s, 3H, -CH3).
3359(s, O-H), 3057 (w, Ar-H), 1593 (C=N), 1610, 9.35 (s, 1H, -OH), 6.78~7.77 (m, 12H, Ar-H), 5.58 (dd, J = 4.8, 12.4 Hz,
1548, 1508, 1470 (s, Ar-C), 1339, 1144 (m,
O=S=O)
3356 (s, O-H), 3067 (w, Ar-H), 1595 (C=N),
1608, 1548, 1497, 1458 (s, Ar-C), 1339, 1125 (m, 1H, Pyrazoline-H), 3.69 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.42
O=S=O)
1H, Pyrazoline-H), 3.86 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.51
(dd, J = 4.8 Hz, J = 17.4 Hz, 1H, Pyrazoline-H), 2.25 (s, 3H, -CH3).
9.36 (s, 1H, -OH), 6.78~7.71 (m, 11H, Ar-H), 5.44 (dd, J = 4.8, 12.4 Hz,
(dd, J = 4.8 Hz, J = 17.4 Hz, 1H, Pyrazoline-H), 2.26 (s, 3H, -CH3).
9.55 (s, 1H, -OH), 9.38 (s, 1H, -OH), 6.75~7.73 (m, 11H, Ar-H), 5.59
(dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-H), 3.67 (s, 3H, -OCH3), 3.86 (dd,
1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.54 (dd, J = 4.8 Hz, J = 17.4 Hz,
1H, Pyrazoline-H), 2.26 (s, 3H, -CH3).
3365 (s, O-H), 3374 (s, O-H), 3067 (w, Ar-H),
1592 (C=N), 1615, 1560, 1495, 1460 (s, Ar-C),
1339, 1125 (m, O=S=O)
12a
12b
12c
12d
12e
3056 (w, Ar-H), 1593 (C=N), 1606, 1545, 1493,
1435 (s, Ar-C), 1319, 1125 (m, O=S=O)
7.20~7.69 (m, 13H, Ar-H), 5.28 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.62 (d, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.40 (dd, J = 4.8 Hz, J
= 17.4 Hz, 1H, Pyrazoline-H), 2.25 (s, 3H, -CH3).
6.75~7.68 (m, 12H, Ar-H), 5.56 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.75 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.58 (dd, J = 4.8 Hz,
J = 17.4 Hz, 1H, Pyrazoline-H), 3.03 (s, 6H, NCH3), 2.19 (s, 3H, -CH3).
7.20~7.80 (m, 12H, Ar-H), 5.26 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.54 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.21 (dd, J = 4.8 Hz,
J = 17.4 Hz, 1H, Pyrazoline-H), 2.18 (s, -3H, -CH3).
7.20~7.80 (m, 12H, Ar-H), 5.18 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.74 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.54 (dd, J = 4.8 Hz,
J = 17.4 Hz, 1H, Pyrazoline-H), 2.20 (s, -3H, -CH3).
7.20~7.74 (m, 11H, Ar-H), 5.28 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.75 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.51 (dd, J = 4.8 Hz,
J = 17.4 Hz, 1H, Pyrazoline-H), 2.19 (s, 3H, -CH3).
3054 (w, Ar-H), 1592(C=N), 1605, 1545, 1496,
1435 (s, Ar-C), 1329, 1145 (m, O=S=O)
3059 (w, Ar-H), 1592 (C=N), 1617, 1540, 1497,
1437 (s, Ar-C), 1339, 1125 (m, O=S=O)
3038 (w, Ar-H), 1592 (C=N), 1607, 1540, 1497,
1437 (s, Ar-C), 1338, 1145 (m, O=S=O)
3057 (w, Ar-H), 1592 (C=N), 1608, 1566, 1498,
1438 (s, Ar-C), 1339, 1125 (m, O=S=O)
258
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J. Chin. Chem. Soc. 2016, 63, 254-260

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Facile Microwave-assisted Synthesis of 1,3,5-trisubstituted Pyrazoline Derivatives
12f
3374 (s, O-H), 3067 (w, Ar-H), 1595 (C=N),
9.55 (s, 1H, -OH), 6.89~7.73 (m, 11H, Ar-H), 5.68 (dd, J = 4.8, 12.4 Hz,
1617, 1587, 1497, 1464 (s, Ar-C), 1337, 1123 (m, 1H, Pyrazoline-H), 3.67 (s, 3H, -OCH3), 3.79 (dd, 1H, J = 12.4, 17.4
O=S=O)
Hz, Pyrazoline-H), 3.51 (dd, J = 4.8 Hz, J = 17.4 Hz, 1H, Pyrazoline-H),
2.18 (s, 3H, -CH3).
13a
13b
3054 (w, Ar-H), 1592 (C=N), 1607, 1547, 1497,
1437 (s, Ar-C), 1339, 1125 (m, O=S=O)
6.93~7.72 (m, 13H, Ar-H), 5.72 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.70 (s, 3H, -OCH3), 3.54 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H),
3.41 (dd, J = 4.8 Hz, J = 17.4 Hz, 1H, Pyrazoline-H), 2.17 (s, 3H, -CH3).
6.80~7.70 (m, 12H, Ar-H), 5.74 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.69 (s, 3H, -OCH3), 3.79 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H),
3.58 (dd, J = 4.8 Hz, J = 17.4 Hz, 1H, Pyrazoline-H), 3.04 (s, 6H,
NCH3), 2.18 (s, 3H, -CH3).
3059 (w, Ar-H), 1592 (C=N), 1612, 1540, 1495,
1434 (s, Ar-C), 1329, 1145 (m, O=S=O)
13c
13d
13e
13f
3068 (w, Ar-H), 1598 (C=N), 1625, 1554, 1508,
1478 (s, Ar-C), 1335, 1134 (m, O=S=O)
6.94~7.83 (m, 12H, Ar-H), 5.48 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.68 (s, 3H, -OCH3), 3.76 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H),
3.51 (dd, J = 4.8 Hz, J = 17.4 Hz, 1H, Pyrazoline-H). 2.15 (s, 3H, -CH3).
6.94~7.83 (m, 12H, Ar-H), 5.48 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.66 (s, 3H, -OCH3), 3.76 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H),
3.41 (dd, J = 4.8 Hz, J = 17.4 Hz, 1H, Pyrazoline-H), 2.17 (s, 3H, -CH3).
6.96~7.67 (m, 11H, Ar-H), 5.78 (dd, J = 4.8, 12.4 Hz, 1H, Pyrazoline-
H), 3.95 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.67 (s, 3H, -OCH3),
3.41 (dd, J = 4.8 Hz, J = 17.4 Hz, 1H, Pyrazoline-H), 2.17 (s, 3H, -CH3).
3055 (w, Ar-H), 1592 (C=N), 1608, 1547, 1498,
1469 (s, Ar-C), 1338, 1142 (m, O=S=O)
3057 (w, Ar-H), 1594 (C=N), 1607, 1548, 1497,
1445 (s, Ar-C), 1336, 1135 (m, O=S=O)
3372 (s, O-H), 3067 (w, Ar-H),1592 (C=N), 1625, 9.68 (s, 1H, -OH), 6.78~7.77 (m, 11H, Ar-H), 5.68 (dd, J = 4.8, 12.4 Hz,
1540, 1495, 1466 (s, Ar-C), 1330, 1133 (m,
O=S=O)
1H, Pyrazoline-H), 3.76 (dd, 1H, J = 12.4, 17.4 Hz, Pyrazoline-H), 3.69
(s, 3H, -OCH3), 3.67 (s, 3H, -OCH3), 3.40 (dd, J = 4.8 Hz, J = 17.4 Hz,
1H, Pyrazoline-H), 2.20 (s, 3H, -CH3).
Res. Chin. Univ. 2013, 29(4), 695.
CONCLUSIONS
An easy and efficient approach has been developed
7. Al-Bogami, A. S. Chem. Res. Chin. Univ. 2014, 30(1), 68.
8. Karabacak, Ç.; Tilki, T.; Tuncer, B. Ö.; Cengiz, M. Res.
Chem. Intermed. 2015, 41, 1985.
for synthesis of trisubstituted pyrazolines via chalcone as
key intermediates reaction with hydrazine under the action
of microwave irradiation. This form of energy is character-
ized by accelerating organic reaction, reduction in reaction
times and improving the economics of the process. This
protocol represents a promising green route for the synthe-
sis of this class of compounds.
9. Bhandari, S.; Tripathi, A. C.; Saraf, K. Med. Chem. Res.
2013, 22, 5290.
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ACKNOWLEDGEMENTS
13. Ovais, S.; Bashir, R.; Yaseen, S.; Rathore, P.; Samim, M.;
Javed, K. Med. Chem. Res. 2013, 22, 1378.
14. Li, M.-M.; Huang, Sh.-Y.; Ye, H.; Ge, F.; Miao, J.-Y.; Zhao,
B.-X. J. Fluoresc. 2013, 23, 799.
This work was supported by the financial support of
the High-talents Project of Shihezi University (No. RCZX
200632). We are grateful to physical and chemical test cen-
ter of Xinjiang University for helps.
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J. Chin. Chem. Soc. 2016, 63, 254-260