One-pot synthesis of 3,5-diphenyl-1h-pyrazoles from chalcones and hydrazine under mechanochemical ball milling

Article abstract of DOI:10.3987/COM-13-12867

A highly efficient and environmentally friendly method has been developed for facile synthesis of 3,5-diphenyl-1H-pyrazoles under mechanochemical ball-milling conditions. The advantages of short reaction time, high efficiency, no separation of in situ generated intermediate, using cheap sodium persulfate as the oxidant, together with very simple work-up procedure, make this one-pot and solvent-free protocol a green and powerful alternative to traditional methods for the synthesis of these kinds of compounds.

Full text of DOI:10.3987/COM-13-12867

HETEROCYCLES, Vol. 89, No. 1, 2014
103
HETEROCYCLES, Vol. 89, No. 1, 2014, pp. 103 - 112. © 2014 The Japan Institute of Heterocyclic Chemistry
Received, 17th October, 2013, Accepted, 25th November, 2013, Published online, 10th December, 2013
DOI: 10.3987/COM-13-12867
ONE-POT SYNTHESIS OF 3,5-DIPHENYL-1H-PYRAZOLES FROM
CHALCONES AND HYDRAZINE UNDER MECHANOCHEMICAL BALL
MILLING
Ze Zhang,* Ya-Jun Tan, Chun-Shan Wang, and Hao-Hao Wu
School of Biological and Chemical Engineering, Anhui Polytechnic University,
Wuhu, Anhui 241000, P. R. China; E-mail: zhangze@ustc.edu.cn
Abstract – A highly efficient and environmentally friendly method has been
developed for facile synthesis of 3,5-diphenyl-1H-pyrazoles under
mechanochemical ball-milling conditions. The advantages of short reaction time,
high efficiency, no separation of in situ generated intermediate, using cheap
sodium persulfate as the oxidant, together with very simple work-up procedure,
make this one-pot and solvent-free protocol a green and powerful alternative to
traditional methods for the synthesis of these kinds of compounds.
INTRODUCTION
It is well known that pyrazole scaffold has been contributing more and more in biological,1
pharmacological,2 food,3 agrochemical fields4 and so on. Due to its scarcity in nature, various methods
have been developed for the synthesis of pyrazoles, among which the most commonly used strategies are:
(a) condensation of 1,3-diketones with hydrazines; (b) 1,3-dipolar cycloadditions of terminal alkynes onto
diazo compounds generated from aldehyde and tosyl hydrazide; (c) reaction of-unsaturated carbonyl
compounds with hydrazines followed by further oxidation. But if a diversity-oriented synthesis of
pyrazoles is desired, method (a) would be somewhat cumbersome as each 1,3-diketone must be purified
and such obtained pyrazole is often a mixture of condensation products. As to method (b), the process
involves diazo compounds, which are well known to be toxic and potentially explosive. Although various
examples have been reported for the synthesis of pyrazoles from -unsaturated carbonyl compounds by
method (c), there are still drawbacks such as rigorous or hazardous conditions, intractable side reactions,
use of organic solvent, long reaction time, tedious procedures and so on. To circumvent these problems,
one of the best alternatives is to carry out this kind of reactions under solvent-free conditions. Among
current solvent-free techniques, mechanical ball-milling has recently been contributing more and more for
efficient promotion of various organic reactions in a greener way.5,6

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Considering the requirement of green chemistry, we have also successfully applied the mechanochemistry
technique in some organic transformation in recent years.7 Herein, we want to report a one-pot and
solvent-free mechanochemical synthesis of various 3,5-diphenyl-1H-pyrazoles from chalcones and
hydrazine, which can be used as a molecular scaffold for the synthesis of apoptosis-inducing agents8 or as
inhibitors of monoamine oxidases.9
RESULTS AND DISCUSSION
We firstly chose chalcone 1a as the model substrate to optimize the best reaction condition. A series of
experiments were carried out in solution and under ball milling by varying the oxidant, the solvent and
the reaction temperature, and the results are summarized in Table 1.
Table 1. Optimization of the reaction conditions for synthesis of 3,5-diphenyl-1H-pyrazole 2a from
chalcone 1a and hydrazinea
O
N
NH
N
NH
.
Oxidant
Time 2
NH2NH2 H2O
Time 1
1a
3
2a
Temperaturec
Time 1/Time 2
(min)
Entry Solvent
Oxidant
Product (Yield)d
(oC)
1
no solventb KMnO4
no solventb I2
rt (20~25)
rt (20~25)
40/60
3 (trace) + 2a (45%)
3 (35%) + 2a (30%)
2
40/60
3
no solventb Mn(OAc)3·2H2O rt (20~25)
no solventb Cu(OAc)2
rt (20~25)
no solventb Ce(NH4)2(NO3)6 rt (20~25)
40/60
3 (67%) + 2a (15%)
4
40/60
3 (83%) + 2a (trace)
3 (trace) + 2a (85%)
3 (trace) + 2a (95%)
1a (22%) + 3 (35%) + 2a (37%)
3 (62%) + 2a (29%)
5
40/60
6
no solventb Na2S2O8
rt (20~25)
rt (20~25)
Refluxing
rt (20~25)
Refluxing
rt (20~25)
80
40/60
7
CH2Cl2
CH2Cl2
THF
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
none
120/120
30/60
8
9
120/120
30/60
1 (trace) + 3 (41%) + 2a (48%)
3 (58%) + 2a (40%)
10
11
12
13
14
15
16
17
THF
DMF
120/120
30/60
3 (20%) + 2a (75%)
DMF
3 (24%) + 2a (70%)
DMSO
DMSO
EtOH
EtOH
EtOH
rt (20~25)
80
120/120
30/60
3 (18%) + 2a (79%)
3 (23%) + 2a (73%)
rt (20~25)
Refluxing
Refluxing
120/120
30/60
1 (trace) + 3 (27%) + 2a (68%)
3 (36%) + 2a (53%)
12 h
3 (30%) + 2a (56%)
aAll reactions were carried out with 1a (2.0 mmol), hydrazine hydrate (2.2 mmol) and second-stepwise added oxidant
(2.5 mmol) unless noted; For ball-milling: 1800 rpm (30 Hz) at room temperature; For stirring in solution: 15 mL solvent
b
c
was employed at room temperature or under refluxing. Carried out under ball-milling. In fact, the temperature in the
ball-milling reaction vessel reached up to 40-50 C after the reaction, varying according to the reaction time.
dDetermined by HPLC analysis.

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Under the condition of ball milling at room temperature, the addition-cyclization of hydrazine with
chalcone 1a to form intermediate pyrazoline 3 can be almost completely accomplished within 40 minutes.
Then we explored several oxidants to convert the in situ generated pyrazoline 3 into pyrazole 2a, and
found that potassium permanganate and iodine afforded rather low chemoselectivity, in which pyrazoline
3 was essentially consumed but the yield of the desired product pyrazole 2a was very poor (entries 1, 2).
This may be ascribed to side reactions resulted from too strong oxidizing capability of the oxidants. As to
Mn(OAc)3 and Cu(OAc)2, they cannot promote the conversion of pyrazoline 3 into pyrazole 2a
efficiently (entries 3, 4). In contrast, Ce(NH4)2(NO3)6 and Na2S2O8 gave a relatively good result,
producing pyrazole 2a in good to excellent yield (entries 5, 6). But with a view to green synthesis
including the factors such as yield, atom economy and cost, Na2S2O8 is undoubtedly the best oxidant for
this transformation.
Using the optimized Na2S2O8 as the oxidant, we also performed several control experiments for this
reaction in various solvents. At room temperature in all these solution cases, a relatively long time of two
hours was needed for complete conversion of starting materials chalcone 1a into pyrazoline 3, which was
obviously slower than that under ball milling condition. When Na2S2O8 was afterward added and further
stirring was kept for two hours, the in situ generated pyrazoline 3 still remained in some extent. It was
noted that strong polarity of the solvent favored the formation of the product pyrazole 2a. For example,
DMF and DMSO (entries 11-14) gave better conversion than that of CH2Cl2 and THF. Under heating, the
first addition-cyclization step became significantly rapid, in which chalcone 1a was consumed within 30
minutes. When Na2S2O8 was added and heating was kept for another hour, both the conversion of
pyrazoline 3 and the yield of pyrazole 2a decreased to a certain extent. The reason may be that Na2S2O8
would decompose when heated in solution, making the desired usage amount of the oxidant insufficient.
On the other hand, we found that even in the absence of any oxidant, pyrazoline 3 can be slowly
converted into pyrazole 2a just by heating in solution. For example, when a mixture of chalcone 1a and
hydrazine was directly refluxed for 12 hours in EtOH, chalcone 1a was also completely consumed,
forming 30% pyrazoline 3 and 56% pyrazole 2a (entry 17). In general, the solvent-free condition of ball
milling at room temperature has obvious advantages including short reaction time, high chemoselectivity
and yield.
Inspired by the results as shown in Table 1, we then employed Na2S2O8 as the oxidant and applied the ball
milling technique to access a wide variety of 3,5-diphenyl-1H-pyrazoles from various chalcones in a
one-pot pathway. Under this mechanically promoted condition, the reactions proceeded cleanly without
intermediate work-up and left no, or only traces of byproducts. The detailed results are outlined in Table
2.

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HETEROCYCLES, Vol. 89, No. 1, 2014
Table 2. Results for mechanochemical synthesis of 3,5-diphenyl-1H-pyrazoles 2 from chalcones 1
O
N
NH
.
1) NH2NH2 H2O
2) Na2S2O8
R1
R2
R1
R2
ball milling
1
2
Time 1/Time 2
Yieldb
Chalcone 1 R1
R2
Pyrazole 2a
(min)
40/60
40/50
45/60
50/65
50/60
50/65
50/65
40/50
40/50
50/60
45/65
50/65
50/75
50/70
50/90
(%)
92
92
85
88
93
80
88
92
90
88
83
89
90
82
86
1
1a
1b
1c
1d
1e
1f
H
H
2a
2b
2c
2d
2e
2f
2
H
4-OMe
4-Cl
3
H
4
H
3, 4-Cl
4-Br
5
H
6
H
4-NO2
3-NO2
H
7
1g
1h
1i
H
2g
2h
2i
8
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-NO2
4-NO2
4-NO2
9
4-OMe
4-Cl
10
11
12
13
14
15
1j
2j
1k
1l
4-NO2
3-NO2
4-Br
2k
2l
1m
1n
1o
2m
2n
2o
4-Cl
4-NO2
aCharacterized by mp, IR, 1H NMR, 13C NMR and HRMS analysis.
bIsolated yield combined from two parallel runs.
From Table 2 it can be seen that the first addition-cyclization step proceeded very smoothly within one
hour in all cases, and substituents in chalcones 1 have no significant effect on this step. This may be
explained that the -unsaturated carbonyl moiety in chalcone exhibits very strong electrophilicity, and
hydrazine has both very strong nucleorphilicity and basicity. These facts make the addition-cyclization of
chalcone with hydrazine fairly easy whether the substituent is electron-donating or electron-withdrawing.
But during the second step for oxidation of in situ generated intermediate pyrazoline into pyrazole, those
cases bearing electron-donating groups exhibited obviously higher reaction activity, thus the reaction time
for full conversion of intermediate pyrazoline into pyrazole was much shorter than those bearing
electron-withdrawing groups. This point is easy to be understood that electron-donating groups cause
electron density in pyrazoline ring very high, which favors the dehydrogenation in the presence of an
oxidant.
In general, all these cases could afford good to excellent yields for the correponding
3,5-diphenyl-1H-pyrazoles, which were obtained just through immersing the resulted reaction mixtures

HETEROCYCLES, Vol. 89, No. 1, 2014
107
into diluted HCl with the aid of ultrasonic irradiation and Büchner filtration. Furthermore, the reaction
process involves no use of organic solvent, and only 10% excessive hydrazine was employed to achieve
complete conversion of chalcone, which is much less than most traditional methods carried out in solution.
1
All the products were well characterized by mp, IR, H NMR, 13C NMR and HRMS analysis. It is
noteworthy that tautomerism was evident in 13C NMR experiments of the 3,5-substituted pyrazoles as
reported,9,10,12 thus sometimes led to difficulty in assigning the corresponding 13C NMR signals.
In conclusion, we have successfully developed a facile, efficient and environmentally friendly method for
synthesis of various 3,5-diphenyl-1H-pyrazoles using mechanochemical ball-milling technique. This
one-pot protocol exhibits the advantages of short reaction time, free use of organic solvent, no separation
of intermediates, low cost, simple work-up procedure, which make it a very efficient and green alternative
to traditional methods for the synthesis of these kinds of compounds.
EXPERIMENTAL
NMR spectra were recorded on a Bruker AV300 or AV400 NMR spectrometer in CDCl3 or DMSO-d6. IR
spectra were recorded on a Bruker VECTOR-22 instrument in KBr pellet. All melting points were
determined on a XT-4 binocular microscope (Beijing Tech Instrument Co., China) and are not corrected.
High resolution mass spectra (HR-MS) were recorded on a Micromass GCT-MS spectrometer with ESI
mode. HPLC was conducted on an Agilent 1100 liquid chromatograph with a diode-array detector using a
Zorbax Eclipse XDB-C18 (4.6 mm × 250 mm) with MeCN:H2O (4:1) as the eluent (2 mL/min), and was
monitored at 254 nm. All ball-milling reactions were performed on mixer mill MM 400 (Retsch GmbH,
Germany). TLC and column chromatography were performed on silica gel GF254, and silica gel H60,
respectively. All other chemicals used in this study were commercially available.
Starting Materials. Chalcones were prepared according to reported method,11 and hydrazine (>99%) was
purchased from Acros.
Typical Procedure for the Preparation of Products 2
Chalcone 1 (2.0 mmol), hydrazine (2.2 mmol) and a stainless ball of 7.0 mm in diameter, were introduced
into a stainless jar (25 mL). The same mixture was also introduced into a second parallel jar. The two
reaction vessels were sealed with screw caps, fixed on the vibration arms of a ball-milling apparatus
(mixer mill MM400, Retsch GmbH, Haan, Germany) and were vibrated vigorously at a rate of 1800
rounds per minute (30 Hz) at room temperature for designated time (Time 1). Then the vessels were
opened and Na2S2O8 (2.5 mmol) were added into the resulted mixtures, and the sealed vessels were
continued to vibrate for designated time (Time 2). The reaction mixtures were immersed in 30 mL water
with the aid of ultrasonic irradiation, and the desired solid products were collected by Büchner filtration,
washed with EtOH/H2O (5 mL/5 mL) and dried in a desiccator.

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3-Phenyl-5-phenyl-1H-pyrazole (2a). Mp 194–196 C (lit.,12 197–199 C); IR (KBr) ν 3241, 2834, 1462,
1274, 1182, 1075, 978, 750, 688 cm-1; 1H NMR (300 MHz, DMSO-d6)  10.40 (brs, 1H, NH), 7.84 (brs,
4H, ArH), 7.45 (brs, 4H, ArH), 7.34 (brs, 2H, ArH), 7.21 (s, 1H, CH) ; 13C NMR (75 MHz, DMSO-d6) 
147.4, 131.3, 128.9, 128.0, 125.2, 99.8; HRMS (ESI) m/z calcd for C15H13N2 (M+H)+: 221.1079, found:
221.1068.
5-(4-Methoxyphenyl)-3-phenyl-1H-pyrazole (2b). Mp 164–166 C (lit.,13 166–168 C); IR (KBr) ν
3029, 2836, 1612, 1510, 1461, 1251, 1169, 1033, 976, 833, 765 cm-1; 1H NMR (300 MHz, CDCl3)  7.71
(d, J = 6.9 Hz, 2H, ArH), 7.62 (d, J = 8.4 Hz, 2H, ArH), 7.31–7.40 (m, 1H, ArH), 7.36 (d, J = 7.5 Hz, 2H,
ArH), 6.90 (d, J = 8.4 Hz, 2H, ArH), 6.74 (s, 1H, CH), 3.82 (s, 3H, OCH3); 13C NMR (75 MHz,
DMSO-d6)  159.0, 143.8, 143.4, 133.8, 128.7, 127.9, 127.6, 126.4, 125.0, 114.2, 98.8, 55.1; HRMS
(ESI) m/z calcd for C16H15N2O (M+H)+: 251.1184, found: 251.1157.
5-(4-Chlorophenyl)-3-phenyl-1H-pyrazole (2c). Mp 212–213 C (lit.,9 217–219 C); IR (KBr) ν 3217,
1
2920, 2850, 1588, 1491, 1448, 1182, 1097, 970, 758, 688 cm-1; H NMR (300 MHz, DMSO-d6)  13.44
(brs, 1H, NH), 7.87 (brs, 2H, ArH), 7.83 (brs, 2H, ArH), 7.52 (brs, 2H, ArH), 7.47 (brs, 2H, ArH), 7.36
(brs, 1H, ArH), 7.23 (s, 1H, CH), 7.13–7.16 (m, 1H, ArH), 6.90–6.96 (m, 2H, ArH), 3.94 (s, 3H, OCH3);
13C NMR (75 MHz, DMSO-d6)  147.2, 142.1, 132.2, 128.8 (3C overlapped), 128.1, 128.0, 126.8, 125.1,
99.9; HRMS (ESI) m/z calcd for C15H12ClN2 (M+H)+: 255.0689, found: 255.0673.
5-(3,4-Dichlorophenyl)-3-phenyl-1H-pyrazole (2d). Mp 194–195 C; IR (KBr) ν 3045, 2913, 2845,
1603, 1432, 1038, 956, 865, 743, 691 cm-1; 1H NMR (300 MHz, DMSO-d6) 13.51 (brs, 1H, NH), 8.07 (s,
1H, ArH), 7.77–7.83 (m, 3H, ArH), 7.68 (s, 1H, ArH), 7.38–7.47 (m, 2H, ArH), 7.31 (s, 1H, ArH), 7.20
(s, 1H, ArH); 13C NMR (75 MHz, DMSO-d6) 149.0, 143.8, 134.3, 130.9, 129.7, 129.0, 128.6, 128.3,
127.6, 126.8, 126.6, 125.1, 100.3; HRMS (ESI) m/z calcd for C15H11Cl2N2 (M+H)+: 289.0299, found:
289.0292; Anal. Calcd for C15H10Cl2N2: C, 62.30; H, 3.49; N, 9.69. Found: C, 62.46; H, 3.53; N, 9.58.
5-(4-Bromophenyl)-3-phenyl-1H-pyrazole (2e). Mp 232–233 C (lit.,14 219–220 C); IR (KBr) ν 3042,
2910, 2844, 1601, 1232, 1057, 955, 793, 689 cm-1; 1H NMR (300 MHz, DMSO-d6)  13.45 (brs, 1H, NH),
7.82 (brs, 4H, ArH), 7.64 (brs, 2H, ArH), 7.48 (brs, 2H, ArH), 7.37 (brs, 1H, ArH), 7.24 (s, 1H, CH); 13C
NMR (75 MHz, DMSO-d6)  150.3, 143.7, 131.6, 129.0, 128.8, 128.2, 128.0, 127.1, 125.1, 120.6, 99.9;
HRMS (ESI) m/z calcd for C15H12BrN2 (M+H)+: 299.0184, found: 299.0175.
5-(4-Nitrophenyl)-3-phenyl-1H-pyrazole (2f). Mp 259–261 C (lit.,8 281 C); IR (KBr) ν 3348, 2916,
2848, 1604, 1516, 1346, 856, 768, 698 cm-1; 1H NMR (300 MHz, DMSO-d6)  13.72 (brs, 1H, NH), 8.29
(d, J = 8.4 Hz, 2H, ArH), 8.12 (d, J = 8.4 Hz, 2H, ArH), 7.81 (d, J = 7.5 Hz, 2H, ArH), 7.37–7.51 (m, 3H,
ArH), 7.34 (s, 1H, CH); 13C NMR (75 MHz, DMSO-d6)  146.9, 145.2, 142.0, 129.5, 128.9, 126.3, 125.6,
124.6, 101.5; HRMS (ESI) m/z calcd for C15H12N3O2 (M+H)+: 266.0930, found: 266.0924.

HETEROCYCLES, Vol. 89, No. 1, 2014
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5-(3-Nitrophenyl)-3-phenyl-1H-pyrazole (2g). Mp 199–201 C (lit.,15 204–205 C); IR (KBr) ν 3125,
1
2918, 2849, 1604, 1513, 1356, 1093, 930, 813, 791 cm-1; H NMR (300 MHz, DMSO-d6)  8.68 (s, 1H,
ArH), 8.31 (d, J = 7.8 Hz, 1H, ArH), 8.18–8.21 (m, 1H, ArH), 7.79–7.87 (m, 2H, ArH), 7.74–7.77 (m, 1H,
ArH), 7.37–7.52 (m, 4H, ArH), 4.58 (brs, 1H, NH); 13C NMR (75 MHz, DMSO-d6)  148.8, 147.6, 146.4,
134.5, 131.8, 130.9, 130.5, 129.4, 128.6, 125.6, 122.6, 119.7, 101.0; HRMS (ESI) m/z calcd for
C15H12N3O2 (M+H)+: 266.0930, found: 266.0928.
3-(4-Methoxyphenyl)-5-phenyl-1H-pyrazole (2h). Mp 158–160 C (lit.,16 160–162 C); IR (KBr) ν
3128, 2921, 2832, 1603, 1504, 1383, 1297, 1034, 931, 828 cm-1; 1H NMR (300 MHz, DMSO-d6)  13.04
(brs, 1H, NH), 7.83 (d, J = 7.3 Hz, 2H, ArH), 7.76 (d, J = 8.8 Hz, 2H, ArH), 7.43 (t, J = 7.5 Hz, 2H, ArH),
13
7.32 (t, J = 7.4 Hz, 1H, ArH), 7.02 (d, J = 8.8 Hz, 2H, ArH), 6.99 (s, 1H, CH), 3.81 (s, 3H, OCH3); C
NMR (75 MHz, DMSO-d6)  158.8, 128.3, 127.2, 126.2, 124.8, 114.0, 98.5, 54.9; HRMS (ESI) m/z calcd
for C16H15N2O (M+H)+: 251.1184, found: 251.1169.
3,5-Bis(4-methoxyphenyl)-1H-pyrazole (2i). Mp 156–157 C (lit.,17 153 C); IR (KBr) ν 3417, 2964,
1
2937, 2840, 1610, 1496, 1440, 1303, 1246, 1110, 1022, 962, 835, 792, 642 cm-1; H NMR (300 MHz,
DMSO-d6)  12.89 (brs, 1H, NH), 7.43 (d, J = 8.8 Hz, 4H, ArH), 7.01 (d, J = 8.8 Hz, 4H, ArH), 6.88 (s,
13
1H, CH), 3.81 (s, 6H, OCH3); C NMR (75 MHz, DMSO-d6)  158.7, 126.1, 113.9, 97.9, 54.9; HRMS
(ESI) m/z calcd for C17H17N2O2 (M+H)+: 281.1290, found: 281.1283.
5-(4-Chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazole (2j). Mp 164–166 C; IR (KBr) ν 3230, 2919,
1
2838, 1666, 1601, 1504, 1255, 1169, 1095, 968, 835, 789 cm-1; H NMR (300 MHz, DMSO-d6) 13.27
(brs, 1H, NH), 7.82 (brs, 2H, ArH), 7.71 (brs, 2H, ArH), 7.53 (brs, 2H, ArH), 7.09 (s, 1H, CH), 7.02 (brs,
13
2H, ArH), 3.77 (s, 3H, OCH3); C NMR (75 MHz, DMSO-d6) 159.5, 141.5, 141.2, 132.0, 130.5, 129.2,
128.5, 127.2, 126.9, 114.7, 99.5, 55.6; HRMS (ESI) m/z calcd for C16H14ClN2O (M+H)+: 285.0795,
found: 285.0782; Anal. Calcd for C16H13ClN2O: C, 67.49; H, 4.60; N, 9.84. Found: C, 67.46; H, 4.65; N,
9.77.
5-(4-Nitrophenyl)-3-(4-methoxyphenyl)-1H-pyrazole (2k). Mp 174–175 C; IR (KBr) ν 3233, 2902,
2861, 1612, 1523, 1374, 1078, 930, 813, 749 cm-1; 1H NMR (300 MHz, DMSO-d6) 13.57 (brs, 1H, NH),
8.31 (d, J = 8.1 Hz, 2H, ArH), 8.13 (d, J = 8.1 Hz, 2H, ArH), 7.77 (d, J = 7.8 Hz, 2H, ArH), 7.32 (s, 1H,
13
CH), 7.07 (d, J = 8.1 Hz, 2H, ArH), 3.82 (s, 3H, OCH3); C NMR (75 MHz, DMSO-d6) 159.7, 149.6,
146.8, 144.5, 140.6, 127.0, 126.2, 124.6, 122.0, 114.8, 100.6, 55.6; HRMS (ESI) m/z calcd for
C16H14N3O3 (M+H)+: 296.1035, found: 296.1031; Anal. Calcd for C16H13N3O3: C, 65.08; H, 4.44; N,
14.23. Found: C, 65.15; H, 4.51; N, 14.19.
5-(3-Nitrophenyl)-3-(4-methoxyphenyl)-1H-pyrazole (2l). Mp 195–196 C; IR (KBr) ν 3337, 2898,
2832, 1608, 1511, 1392, 1338, 1108, 938, 846, 754 cm-1; 1H NMR (300 MHz, DMSO-d6) 13.45 (brs, 1H,

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NH), 8.62 (s, 1H, ArH), 8.28 (d, J = 7.8 Hz, 1H, ArH), 8.15 (d, J = 8.1 Hz, 1H, ArH), 7.69–7.76 (m, 3H,
ArH), 7.30 (s, 1H, CH), 7.04 (d, J = 8.7 Hz, 2H, ArH), 3.79 (s, 3H, OCH3); 13C NMR (75 MHz,
DMSO-d6) 159.8, 148.8, 144.0, 142.5, 136.7, 131.7, 130.7, 127.0, 122.4, 122.1, 119.6, 114.9, 99.9, 55.6;
HRMS (ESI) m/z calcd for C16H14N3O3 (M+H)+: 296.1035, found: 296.1027; Anal. Calcd for C16H13N3O3:
C, 65.08; H, 4.44; N, 14.23. Found: C, 65.17; H, 4.52; N, 14.16.
5-(4-Bromophenyl)-3-(4-nitrophenyl)-1H-pyrazole (2m). Mp 243–244 C; IR (KBr) ν 3277, 3001,
1
2938, 2844, 1597, 1515, 1487, 1351, 1237, 1055, 936, 742 cm-1; H NMR (300 MHz, DMSO-d6) 13.75
(brs, 1H, NH), 8.27–8.35 (m, 2H, ArH), 8.06–8.12 (m, 2H, ArH), 7.61–7.84 (m, 4H, ArH), 7.45 (s, 1H,
CH); 13C NMR (75 MHz, DMSO-d6) 149.5, 146.4, 142.9, 139.8, 131.6, 128.1, 127.1, 125.8, 124.1, 121.5,
101.4; HRMS (ESI) m/z calcd for C15H11BrN3O2 (M+H) +: 344.0035, found: 344.0024; Anal. Calcd for
C15H10BrN3O2: C, 52.35; H, 2.93; N, 12.21. Found: C, 52.39; H, 2.94; N, 12.24.
5-(4-Chlorophenyl)-3-(4-nitrophenyl)-1H-pyrazole (2n). Mp 234–236 C; IR (KBr) ν 3431, 2916,
2850, 1602, 1516, 1491, 1344, 976, 852 cm-1; 1H NMR (300 MHz, CDCl3) 8.31 (d, J = 9.0 Hz, 2H, ArH),
7.96 (d, J = 8.7 Hz, 2H, ArH), 7.60 (d, J = 8.4 Hz, 2H, ArH), 7.46 (d, J = 8.7 Hz, 2H, ArH), 6.94 (s, 1H,
CH); 13C NMR (75 MHz, DMSO-d6) 146.5, 144.3, 143.8, 143.6, 129.6, 129.1, 128.5, 126.9, 125.8, 121.4,
101.5; HRMS (ESI) m/z calcd for C15H11ClN3O2 (M+H)+: 300.0540, found: 300.0531; Anal. Calcd for
C15H10ClN3O2: C, 60.11; H, 3.36; N, 14.02. Found: C, 60.20; H, 3.31; N, 13.93.
3,5-Bis(4-nitrophenyl)-1H-pyrazole (2o). Mp 257–258 C (lit.,18 266 C); IR (KBr) ν 3273, 2925, 2843,
1
1597, 1516, 1478, 1355, 1237, 1074, 915, 707 cm-1; H NMR (300 MHz, DMSO-d6)  14.07 (brs, 1H,
NH), 8.30–8.39 (m, 4H, ArH), 8.07–8.16 (m, 4H, ArH), 7.69 (s, 1H, CH); 13C NMR (75 MHz, DMSO-d6)
 147.0, 139.1, 129.5, 124.6, 101.5; HRMS (ESI) m/z calcd for C15H11N4O4 (M+H)+: 311.0780, found:
311.0773.
ACKNOWLEDGEMENTS
We are grateful for the financial support from National Natural Science Foundation of China (21242013,
20902002) and Anhui Provincial Natural Science Foundation (No. 10040606Q04).
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