A facile access to 1,3,4-trisubstituted pyrazoles via 1,3-dipolar cycloaddition of 3-arylsydnones with α,β-unsaturated ketones

Article abstract of DOI:10.1007/s00706-012-0901-7

A novel one-pot synthesis of 1,3,4-trisubstituted pyrazoles has been accomplished by 1,3-dipolar cycloaddition of α,β-unsaturated ketones and 3-arylsydnones in dry xylene. The structural identities of these compounds were confirmed on the basis of IR, NMR, mass spectral, and X-ray analysis.

Full text of DOI:10.1007/s00706-012-0901-7

Monatsh Chem (2013) 144:879–884
DOI 10.1007/s00706-012-0901-7
ORIGINAL PAPER
A facile access to 1,3,4-trisubstituted pyrazoles via 1,3-dipolar
cycloaddition of 3-arylsydnones with a,b-unsaturated ketones
•
•
•
Fei Chen Fang-Ming Liu Hai Shi
Sen-Lin Chen
Received: 7 March 2012 / Accepted: 9 December 2012 / Published online: 31 January 2013
Ó Springer-Verlag Wien 2013
Abstract A novel one-pot synthesis of 1,3,4-trisubsti-
tuted pyrazoles has been accomplished by 1,3-dipolar
cycloaddition of a,b-unsaturated ketones and 3-arylsyd-
nones in dry xylene. The structural identities of these
compounds were confirmed on the basis of IR, NMR, mass
spectral, and X-ray analysis.
compounds (or their 1,3-dielectrophilic equivalents) or the
generation of one C–N bond and one C–C bond by intermo-
lecular [3?2]-cycloadditions of 1,3-dipoles to dipolarophiles.
Each method has its own scope and efficiency limitations.
Recently, Fustero et al. [9] published a review of the
synthetic methods leading to pyrazoles. The most com-
monly used method for the preparation of pyrazoles
involves the cyclocondensation of an appropriate hydrazine
(mainly arylhydrazines), which acts as a double nucleo-
phile, with a three-carbon unit featuring two electrophilic
carbons in a 1,3-relationship, such as 1,3-dicarbonyl, a,b-
unsaturated carbonyl compounds [3, 10–12], b-enaminon-
es, or related compounds [13–15] (Scheme 1). Compared
to the classic cyclocondensation reaction between hydra-
zines and 1,3-diketones, in which the regioselectivity relies
on the different reactivity of the two carbonyl groups, 1,3-
dipolar cycloadditions are intrinsically more regioselective
owing to the significant electronegativity difference
between the N and C atoms of the substrate. Three main
classes of 1,3-dipoles have been used as the [CNN] frag-
ment for the synthesis of the pyrazole skeleton, namely
diazoalkanes, nitrilimines, and azomethine imines; the
[CC] fragment would come from alkenes or alkynes.
Sydnones are relatively stable mesoionic compounds that
can react as azomethine imine-type dipoles. Recently, the
1,3-dipolar cycloaddition of sydnones to acetylenic ketones
to afford pyrazoles was reported [16]. We found that
replacing acetylenic ketones with unsymmetrical prope-
nones (a,b-unsaturated ketones) can also afford 1,3,4-
trisubstituted pyrazoles.
Keywords Pyrazole Á Crystal structure Á
1,3-Dipolar cycloaddition
Introduction
The synthesis of pyrazoles has received considerable
attention due to their versatile biological activities, e.g.,
anti-inflammatory, anticoagulant, antibacterial, and antitu-
mor agents, CDK inhibitors, and cyclooxygenase-2 (Cox-
2) inhibitors [1–7]. The pyrazole motif also makes up the
core structure of some well-known drugs (e.g., Viagra,
Acomplia, and Celebrex) [8].
Conventional approaches for the preparation of substi-
tuted pyrazoles involve either the construction of two C–N
bonds by condensation of hydrazines with 1,3-dicarbonyl
F. Chen (&) Á F.-M. Liu
College of Chemistry and Chemical Engineering,
Xinjiang University, Urumqi 830046, People’s Republic
of China
e-mail: cf8156lei@sina.com
F.-M. Liu
e-mail: fmliu859@sohu.com
Encouraged by all these facts and in continuation of our
previous work on the synthesis of novel heterocycles
employing 1,3-dipolar cycloaddition, we herein report a
simple and convenient method for one-pot synthesis of
pyrazoles. The synthetic route is shown in Scheme 2.
H. Shi Á S.-L. Chen
College of Materials and Chemical Engineering,
Hangzhou Normal University, Hangzhou 310036,
People’s Republic of China
123

880
F. Chen et al.
Scheme 1
Scheme 2
Results and discussion
(enumerated clockwise and starting with N(1)–N(2)–C(7)–
C(8)): 1.0(4)°, -1.1(4)°, -176.7(3)°, 0.2(4)°, -0.5(4)°,
and it adopts an envelope conformation with atom C(7)
deviating from the plane defined by N(1), N(2), C(8), and
As part of our ongoing development of efficient protocols
for the preparation of pyrazole derivatives, this study
reports for the first time the regiospecific synthesis of 1,3,4-
trisubstituted pyrazoles by 1,3-dipolar cycloaddition of
a,b-unsaturated ketones [17] and 3-arylsydnones [18] in
refluxing dry xylene. All of the products were separated by
column chromatography on silica gel and characterized by
IR, NMR, mass spectral, and X-ray analysis.
The 1H NMR of compound 3 contained one singlet
approximately at 8.25 ppm corresponding to the proton of
pyrazole. In addition, aromatic protons appeared in the
range 7.90–6.86 ppm. Their infrared spectra contained
strong absorption bands for C=O and C=N double bonds at
1,632 and 1,583 cm-1. Also, in all cases molecular ion
peaks of all target compounds were observed in the mass
spectra.
˚
C(9) of -0.0139 A. In addition, the dihedral angle and
the distances of the aromatic ring Cg2 (C(1)–C(6)), Cg3
(C(11)–C(12)–C(13)–C(14)–C(16)–C(17)), Cg4 (C(18)–
C(19)–C(20)–C(21)–C(23)–C(24)), and pyrazole ring Cg1
˚
˚
˚
are 23.73°, 4.015 A; 54.73°, 4.759 A; and 29.88°, 3.930 A,
respectively. Detailed information about the crystal data
and structure determination is summarized in Table 1.
Selected bond lengths and angles are tabulated in Table 2.
The crystal is stabilized by weak hydrogen bonds which are
described in Table 3.
In conclusion, we have obtained a series of 1-(4-
substituted phenyl)-3-(4-substituted benzoyl)-4-(4-substi-
tuted phenyl)pyrazole derivatives 3a–3r by 1,3-dipolar
cycloaddition reaction. The molecular conformation of the
title compounds was further confirmed by X-ray analysis of
compound 3q as a typical example.
The structure of the crystal 3q is displayed in Fig. 1.
The pyrazole ring is characterized by the torsion angles
123

A facile access to 1,3,4-trisubstituted pyrazoles
881
˚
Table 2 Selected bond lengths/A and angles/° of compound 3q
N(1)–C(9)
N(1)–N(2)
N(2)–C(7)
N(2)–C(18)
C(6)–C(8)
C(7)–C(8)
C(8)–C(9)
C(9)–C(10)
O(1)–C(10)
O(2)–C(15)
1.392(5)
1.348(4)
1.359(4)
1.423(4)
1.489(4)
1.316(4)
1.422(4)
1.464(4)
1.228(4)
1.413(5)
N(1)–N(2)–C(7)
N(1)–N(2)–C(18)
N(2)–N(1)–C(9)
N(1)–C(9)–C(8)
C(7)–N(2)–C(18)
C(7)–C(8)–C(9)
C(8)–C(9)–C(10)
C(9)–C(8)–C(6)
C(9)–C(10)–C(11)
O(1)–C(10)–C(9)
111.5(3)
127.7(3)
107.2(3)
104.1(3)
120.8(2)
111.0(3)
132.4(3)
131.8(3)
118.6(3)
121.6(3)
˚
Table 3 Intermolecular and intramolecular interactions/A in com-
pound 3q
D–HÁÁÁA
Intermolecular interactions/A in the compound
C(5)–H(5A)ÁÁÁO(1) 0.93 2.44
Intramolecular interactions/A in the compound
D–H
HÁÁÁA
DÁÁÁA
D–HÁÁÁA
˚
3.024(4) 121
˚
C(15)–H(15B)ÁÁÁO(1)a
C(2)–H(2A)ÁÁÁCg(4)b
C(4)–H(4A)ÁÁÁCg(3)c
C(22)–H(22C)ÁÁÁCg(1)d
0.96
49
2.46
2.93
2.81
2.82
3.330(5) 151
3.597(4) 130
3.710(4) 164
3.668(5) 147
72
70
a
X,-1 ? Y,Z
b
X,1 ? Y,Z
c
Fig. 1 Molecular structure of 3q
2 - X,1 - Y,1 - Z
d
3 - X,-Y,-Z
Table 1 Crystal data and structure refinement for compound 3q
Empirical formula
Formula weight
Temperature/K
Crystal system
Space group
C24H19ClN2O2
402.86
Experimental
Reactions were monitored by TLC. Melting points were
determined by use of a Mettler FP-5 melting point appa-
ratus. IR spectra were recorded as KBr pellets on a Bruker
Equinox 55 FT-IR spectrophotometer. NMR spectra were
recorded on a Bruker 400 MHz spectrometer using TMS as
internal reference. Mass spectra were acquired with an
Agilent 5975 instrument (EI, 70 eV). X-ray diffraction data
were collected on a Hitachi F-4500 R-Axis Spider
diffractometer.
293(2)
Triclinic
P-1
˚
a/A
8.5673(8)
˚
b/A
8.7058(7)
˚
c/A
14.1278(13)
107.109(2)
90.274
a/°
b/°
c/°
98.381(2)
3
˚
V/A
995.07(15)
2
General procedure for the preparation of 1-(4-
substituted phenyl)-3-(4-substituted benzoyl)-4-(4-
substituted phenyl)pyrazoles 3a–3r
Z
D
calc/g m-3
1.345
Crystal size/mm
0.48 9 0.34 9 0.20
3.02–27.47
0.215
h range/°
l/mm-1
3-Arylsydnone 2 (1 mmol) and chalcones 1 (1 mmol) were
dissolved in 10 cm3 dry xylene and refluxed for 10 h. After
completion of the reaction (monitored by TLC and evolu-
tion of CO2) the solvent was removed by distillation under
reduced pressure. The resulting crude product was purified
by column chromatography with ethyl acetate/petroleum
Reflections collected
Data/restraints/parameters
Final R indices [I [ 2r(I)]
R indices (all data)
9,773
4,514/0/263
R1 = 0.1072, xR2 = 0.2519
R1 = 0.0666, xR2 = 0.1924
123

882
F. Chen et al.
OCH3), 2.35 (s, 3H, CH3) ppm; 13C NMR (100 MHz,
CDCl3): d = 188.88, 163.38, 153.89, 139.43, 138.46,
132.04, 131.64, 131.52, 129.68, 129.27, 129.03, 127.40,
128.66, 121.28, 119.54, 113.66, 55.60, 21.26 ppm; IR
ether (1:8; v/v) as eluent to afford the corresponding pyr-
azole derivatives 3a–3r.
3-Benzoyl-1,4-diphenylpyrazole (3a, C22H16N2O)
Light yellow crystals; yield 45 %; Rf = 0.46; m.p.: 140–
ꢀ
(KBr): m = 2,971 (Ar–H), 1,633 (C=O), 1,583, 1,508,
1
142 °C (156–158 °C [18]); H NMR (400 MHz, CDCl3):
1,395 (C=N, C=C) cm-1; MS: m/z = 368 (M?).
d = 8.24 (s, 1H, pyrazole-H), 7.88–7.30 (m, 15H, Ph-H)
ppm; 13C NMR (100 MHz, CDCl3): d = 188.72, 163.04,
153.01, 137.21, 136.19, 131.71, 131.38, 131.32, 131.14,
129.85, 128.53, 128.19, 127.98, 120.93, 119.82,
3-(4-Chlorobenzoyl)-4-(4-methylphenyl)-1-phenylpyrazole
(3f, C23H17ClN2O)
Yellow crystals; yield 42 %; Rf = 0.48; m.p.: 140–143 °C;
ꢀ
1H NMR (400 MHz, CDCl3): d = 8.26 (s, 1H, pyrazole-
114.29 ppm; IR (KBr): m = 2,980 (Ar–H), 1,632 (C=O),
H), 7.56–7.14 (m, 13H, Ar–H), 2.36 (s, 3H, CH3) ppm; 13
C
1,581, 1,508, 1,397 (C=N, C=C) cm-1; MS: m/z = 324
(M?).
NMR (100 MHz, CDCl3): d = 188.65, 163.33, 153.89,
139.43, 138.52, 132.04, 131.64, 131.44, 129.68, 129.30,
129.10, 128.66, 127.36, 121.28, 119.55, 113.66, 21.22 pm;
3-(4-Methoxybenzoyl)-1,4-diphenylpyrazole
(3b, C23H18N2O2)
Light yellow crystals; yield 48 %; Rf = 0.45; m.p.: 112–
ꢀ
IR (KBr): m = 2,968 (Ar–H), 1,633 (C=O), 1,583, 1,506,
1,394 (C=N, C=C), 756 (C–Cl) cm-1; MS: m/z = 372
1
114 °C; H NMR (400 MHz, CDCl3): d = 8.25 (s, 1H,
(M?).
pyrazole-H), 7.89–6.90 (m, 14H, Ar–H), 3.86 (s, 3H,
OCH3) ppm; 13C NMR (100 MHz, CDCl3): d = 188.84,
163.38, 153.69, 139.27, 138.33, 132.01, 131.93, 131.53,
129.57, 128.91, 128.45, 127.69, 121.36, 119.42, 113.55,
3-Benzoyl-1-(4-methylphenyl)-4-phenylpyrazole
(3g, C23H18N2O)
Light yellow crystals; yield 45 %; Rf = 0.46; m.p.: 143–
1
ꢀ
145 °C; H NMR (400 MHz, CDCl3): d = 8.25 (s, 1H,
55.44 ppm; IR (KBr): m = 2,977 (Ar–H), 1,633 (C=O),
1,582, 1,507, 1,397 (C=N, C=C) cm-1; MS: m/z = 354
pyrazole-H), 7.89–7.29 (m, 14H, Ar–H), 2.41 (s, 3H, CH3)
ppm; 13C NMR (100 MHz, CDCl3): d = 189.78, 163.02,
153.12, 137.26, 136.59, 132.31, 131.99, 131.78, 129.85,
129.21, 128.62, 128.29, 128.08, 127.87, 120.61, 119.22,
(M?).
3-(4-Chlorobenzoyl)-1,4-diphenylpyrazole
(3c, C22H15ClN2O)
ꢀ
20.88 ppm; IR (KBr): m = 2,980 (Ar–H), 1,632 (C=O),
Yellow crystals; yield 41 %; Rf = 0.48; m.p.: 134–136 °C;
1H NMR (400 MHz, CDCl3): d = 8.26 (s, 1H, pyrazole-
H), 7.54–7.15 (m, 14H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 188.64, 163.38, 153.49, 139.27, 138.30,
132.20, 131.93, 131.64, 131.12, 129.55, 128.90, 128.55,
1,581, 1,508, 1,395 (C=N, C=C) cm-1; MS: m/z = 338
(M?).
3-(4-Methoxybenzoyl)-1-(4-methylphenyl)-4-phenylpyra-
zole (3h, C24H20N2O2)
Light yellow crystals; yield 46 %; Rf = 0.45; m.p.: 134–
ꢀ
127.52, 121.26, 119.43, 113.75 ppm; IR (KBr): m = 2,978
(Ar–H), 1,632 (C=O), 1,583, 1,516, 1,394 (C=N, C=C),
1
137 °C; H NMR (400 MHz, CDCl3): d = 8.24 (s, 1H,
756 (C–Cl) cm-1; MS: m/z = 358 (M?).
pyrazole-H), 7.90–6.89 (m, 13H, Ar–H), 3.86 (s, 3H,
OCH3), 2.36 (s, 3H, CH3) ppm; 13C NMR (100 MHz,
CDCl3): d = 188.74, 163.09, 153.11, 137.21, 136.69,
131.88, 131.71, 131.32, 131.14, 129.85, 128.53, 128.19,
127.98, 120.93, 119.22, 113.29, 55.23, 20.89 ppm; IR
3-Benzoyl-4-(4-methylphenyl)-1-phenylpyrazole
(3d, C23H18N2O)
Light yellow crystals; yield 44 %; Rf = 0.46; m.p.: 105–
1
107 °C; H NMR (400 MHz, CDCl3): d = 8.25 (s, 1H,
ꢀ
(KBr): m = 2,982 (Ar–H), 1,633 (C=O), 1,584, 1,510,
1,397 (C=N, C=C) cm-1; MS: m/z = 368 (M?).
pyrazole-H), 7.89–7.29 (m, 14H, Ar–H), 2.40 (s, 3H, CH3)
ppm; 13C NMR (100 MHz, CDCl3): d = 188.65, 163.34,
153.69, 139.27, 138.43, 132.06, 131.83, 131.64, 139.34,
139.20, 129.52, 128.91, 128.53, 121.16, 119.42, 113.55,
3-(4-Chlorobenzoyl)-1-(4-methylphenyl)-4-phenylpyrazole
(3i, C23H17ClN2O)
Yellow crystals; yield 43 %; Rf = 0.47; m.p.: 159–162 °C;
ꢀ
21.35 ppm; IR (KBr): m = 2,970 (Ar–H), 1,632 (C=O),
1H NMR (400 MHz, CDCl3): d = 8.26 (s, 1H, pyrazole-
1,582, 1,509, 1,394 (C=N, C=C) cm-1; MS: m/z = 338
H), 7.56–7.13 (m, 13H, Ar–H), 2.38 (s, 3H, CH3) ppm; 13
C
(M?).
NMR (100 MHz, CDCl3): d = 188.60, 163.03, 153.21,
137.21, 136.69, 131.88, 131.71, 131.14, 131.12, 129.76,
128.53, 128.19, 127.98, 120.93, 119.02, 113.12,
3-(4-Methoxybenzoyl)-4-(4-methylphenyl)-1-phenylpyra-
zole (3e, C24H20N2O2)
Light yellow crystals; yield 45 %; Rf = 0.45; m.p.: 145–
ꢀ
20.96 ppm; IR (KBr): m = 2,973 (Ar–H), 1,632 (C=O),
1
1,581, 1506, 1,397 (C=N, C=C), 758 (C–Cl) cm-1; MS:
148 °C; H NMR (400 MHz, CDCl3): d = 8.25 (s, 1H,
pyrazole-H), 7.89–6.89 (m, 13H, Ar–H), 3.86 (s, 3H,
m/z = 372 (M?).
123

A facile access to 1,3,4-trisubstituted pyrazoles
883
3-Benzoyl-1,4-bis(4-methylphenyl)pyrazole
(3j, C24H20N2O)
Light yellow crystals; yield 45 %; Rf = 0.47; m.p.: 126–
129.39, 128.15, 127.30, 119.24, 113.43, 55.29 ppm; IR
ꢀ
(KBr): m = 2,977 (Ar–H), 1,633 (C=O), 1,583, 1,507,
1,395 (C=N, C=C), 755 (C–Cl) cm-1; MS: m/z = 388
1
130 °C; H NMR (400 MHz, CDCl3): d = 8.25 (s, 1H,
(M?).
pyrazole-H), 7.89–7.24 (m, 13H, Ar–H), 2.40, 2.38 (2 s,
6H, CH3) ppm; 13C NMR (100 MHz, CDCl3): d = 189.78,
163.29, 153.64, 138.15, 137.14, 136.67, 132.23, 132.02,
129.81, 129.18, 128.52, 128.07, 127.48, 120.46, 119.19,
3-(4-Chlorobenzoyl)-4-(4-chlorophenyl)-1-phenylpyrazole
(3o, C22H14Cl2N2O)
Yellow crystals; yield 38 %; Rf = 0.50; m.p.: 98–102 °C;
1H NMR (400 MHz, CDCl3): d = 8.28 (s, 1H, pyrazole-
H), 7.50–7.28 (m, 13H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 188.52, 162.84, 152.78, 137.21, 136.19,
131.71, 131.38, 131.32, 131.14, 129.85, 128.53, 128.19,
ꢀ
112.52, 21.09, 20.80 ppm; IR (KBr): m = 2,989 (Ar–H),
1,632 (C=O), 1,583, 1,509, 1,398 (C=N, C=C) cm-1; MS:
m/z = 352 (M?).
ꢀ
3-(4-Methoxybenzoyl)-1,4-bis(4-methylphenyl)pyrazole
(3k, C25H22N2O2)
Light yellow crystals; yield 47 %; Rf = 0.47; m.p.: 146–
127.98, 120.93, 119.82, 114.06 ppm; IR (KBr): m = 2,974
(Ar–H), 1,630 (C=O), 1,582, 1,506, 1,394 (C=N, C=C),
755 (C–Cl) cm-1; MS: m/z = 392 (M?).
1
150 °C; H NMR (400 MHz, CDCl3): d = 8.24 (s, 1H,
3-Benzoyl-4-(4-chlorophenyl)-1-(4-methylphenyl)pyrazole
(3p, C23H17ClN2O)
Light yellow crystals; yield 40 %; Rf = 0.50; m.p.: 155–
pyrazole-H), 7.89–6.86 (m, 12H, Ar–H), 3.86 (s, 3H,
OCH3), 2.39, 2.38 (2 s, 6H, CH3) ppm; 13C NMR
(100 MHz, CDCl3): d = 188.64, 162.94, 153.20, 146.65,
138.03, 136.99, 131.63, 131.22, 131.19, 130.07, 129.77,
128.96, 128.60, 120.67, 119.09, 113.24, 55.19, 21.04,
1
160 °C; H NMR (400 MHz, CDCl3): d = 8.26 (s, 1H,
pyrazole-H), 7.56–7.14 (m, 13H, Ar–H), 2.37 (s, 3H, CH3)
ppm; 13C NMR (100 MHz, CDCl3): d = 188.74, 163.09,
153.11, 137.21, 136.69, 131.88, 131.61, 131.33, 131.04,
129.85, 128.53, 128.16, 127.98, 120.94, 119.20, 113.29,
ꢀ
20.72 ppm; IR (KBr): m = 2,979 (Ar–H), 1,632 (C=O),
1,583, 1,506, 1,392 (C=N, C=C) cm-1; MS: m/z = 382
(M?).
ꢀ
20.86 ppm; IR (KBr): m = 2,981 (Ar–H), 1,632 (C=O),
3-(4-Chlorobenzoyl)-1,4-bis(4-methylphenyl)pyrazole
(3l, C24H19ClN2O)
1,582, 1,508, 1,397 (C=N, C=C), 756 (C–Cl) cm-1; MS:
m/z = 372 (M?).
Yellow crystals; yield 43 %; Rf = 0.49; m.p.: 170–175 °C;
1H NMR (400 MHz, CDCl3): d = 8.25 (s, 1H, pyrazole-
H), 7.56–6.88 (m, 12H, Ar–H), 2.38 (2 s, 6H, CH3) ppm;
13C NMR (100 MHz, CDCl3): d = 188.44, 162.98, 153.30,
146.65, 137.86, 136.99, 131.63, 131.22, 131.19, 129.77,
130.02, 128.96, 128.68, 120.67, 119.09, 113.24, 21.14,
4-(4-Chlorophenyl)-3-(4-methoxybenzoyl)-1-(4-methyl-
phenyl)pyrazole (3q, C24H19ClN2O2)
Yellow crystals; yield 44 %; Rf = 0.48; m.p.: 194–197 °C;
1H NMR (400 MHz, CDCl3): d = 8.26 (s, 1H, pyrazole-
H), 7.90–6.89 (m, 13H, Ar–H), 3.88 (s, 3H, OCH3), 2.38 (s,
3H, CH3) ppm; 13C NMR (100 MHz, CDCl3): d = 188.64,
162.94, 153.20, 146.65, 138.03, 136.99, 131.63, 131.22,
131.19, 130.07, 129.77, 128.96, 128.60, 120.67, 119.09,
ꢀ
20.92 ppm; IR (KBr): m = 2,973 (Ar–H), 1,632 (C=O),
1,582, 1,506, 1,397 (C=N, C=C), 758 (C–Cl) cm-1; MS:
m/z = 386 (M?).
ꢀ
113.24, 55.19, 21.14 ppm; IR (KBr): m = 2,972 (Ar–H),
1,633 (C=O), 1,583, 1,509, 1,396 (C=N, C=C), 756 (C–Cl)
3-Benzoyl-4-(4-chlorophenyl)-1-phenylpyrazole
(3m, C22H15ClN2O)
cm-1; MS: m/z = 402 (M?).
Yellow crystals; yield 40 %; Rf = 0.48; m.p.: 147–149 °C;
1H NMR (400 MHz, CDCl3): d = 8.27 (s, 1H, pyrazole-
H), 7.56–7.30 (m, 14H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 188.70, 163.04, 153.01, 137.31, 136.26,
131.71, 131.38, 131.36, 131.16, 129.88, 128.53, 128.18,
3-(4-Chlorobenzoyl)-4-(4-chlorophenyl)-1-(4-methyl-
phenyl)pyrazole (3r, C23H16Cl2N2O)
Yellow crystals; yield 40 %; Rf = 0.48; m.p.: 198–201 °C;
1H NMR (400 MHz, CDCl3): d = 8.26 (s, 1H, pyrazole-
H), 7.50–7.12 (m, 12H, Ar–H), 2.40 (s, 3H, CH3) ppm; 13
C
ꢀ
127.98, 120.94, 119.82, 114.31 ppm; IR (KBr): m = 2,970
(Ar–H), 1,632 (C=O), 1,583, 1,508, 1,396 (C=N, C=C),
NMR (100 MHz, CDCl3): d = 188.59, 163.00, 153.21,
137.21, 136.66, 131.88, 131.70, 131.34, 131.18, 129.85,
128.54, 128.19, 127.96, 120.93, 119.21, 113.29, 20.89 ppm;
756 (C–Cl) cm-1; MS: m/z = 358 (M?).
ꢀ
4-(4-Chlorophenyl)-3-(4-methoxybenzoyl)-1-phenylpyra-
zole (3n, C23H17ClN2O2)
IR (KBr): m = 2,983 (Ar–H), 1,631 (C=O), 1,582, 1,506,
1,397 (C=N, C=C), 758 (C–Cl) cm-1; MS: m/z = 406 (M?).
Yellow crystals; yield 44 %; Rf = 0.47; m.p.: 175–177 °C;
1H NMR (400 MHz, CDCl3): d = 8.26 (s, 1H, pyrazole-
H), 7.56–6.90 (m, 13H, Ar–H), 3.86 (s, 3H, OCH3) ppm;
13C NMR (100 MHz, CDCl3): d = 188.17, 163.21, 153.23,
138.86, 137.86, 132.88, 131.66, 131.61, 131.00, 129.77,
X-ray crystallography
CCDC-870067 contains the supplementary crystallographic
data for compound 3q. These data can be obtained free of
123

884
F. Chen et al.
7. Penning TD, Talley JJ, Bertenshaw SR, Carter JS, Collins PW,
Docter S, Graneto MJ, Lee LF, Malecha JW, Miyashiro JM,
Rogers RS, Rogier DJ, Yu SS, Anderson GD, Burton EG, Cog-
burn JN, Gregory SA, Koboldt CM, Perkins WE, Seibert K,
Veenhuizen AW, Zhang YY, Isakson PC (1997) J Med Chem
40:1347
charge from the Cambridge Crystallographic Data Centre
(CCDC) via e-mail: deposit@ccdc.cam.ac.uk.
Acknowledgments We are grateful to the Key SCI-Tech Innova-
tion Team of Zhejiang Province (2010R5 0017) for financial help.
8. Elguero J, Goya P, Jagerovic N, Silva AMS (2002) In: Attanasi
OA, Spinelli D (eds) Targets in heterocyclic systems—chemistry
and properties, vol 6. Italian Society of Chemistry, Rome, p 52
References
´
´ ´
9. Fustero S, Sanchez-Rosello M, Barrio P, Simon-Fuentes A (2011)
1. Gomez L, Hack MD, Wu J, Wiener JJM, Venkatesan HAS,
Pippel DJ, Mani N, Morrow BJ, Motley ST, Shaw KJ, Wolin R,
Grice CA, Jones TK (2007) Bioorg Med Chem Lett 17:2723
2. Regan J, Breitfelder S, Cirillo P, Gilmore T, Graham AG, Hickey
E, Klaus B, Madwed J, Moriak M, Moss N, Pargellis C, Pav S,
Proto A, Swinamer A, Tong L, Torcellini C (2002) J Med Chem
45:2994
3. Pinto DJP, Orwat MJ, Koch S, Rossi KA, Alexander RS,
Smallwood A, Wong PC, Rendina AR, Luettgen JM, Knabb RM,
He K, Xin B, Wexler RR, Lam PYS (2007) J Med Chem 50:5339
4. Ghotekar BK, Ghagare MG, Toche RB, Jachak MN (2010)
Monatsh Chem 141:169
Chem Rev 111:6984
10. Martins MAP, Peres RL, Frizzo CP, Scapin E, Moreira DN, Fiss GF,
Zanatta N, Bonacorso HG (2009) J Heterocycl Chem 46:1247
11. Reidlinger C, Dworczak R, Junek H (1998) Monatsh Chem
129:1207
12. Silva VLM, Silva AMS, Pinto DCGA, Jagerovic N, Callado LF,
Cavaleiro JAS, Elguero J (2007) Monatsh Chem 138:797
13. Chimenti F, Bolasco A, Manna F, Secci D, Chimenti P, Granese
A, Befani O, Turini P, Alcaro S, Ortuso F (2006) Chem Biol Drug
Des 67:206
14. Nikpour F, Beigvand M (2008) Monatsh Chem 139:821
15. Makino K, Kim HS, Kurasawa Y (1998) J Heterocycl Chem
35:489
16. Hegde JC, Rai G, Puranik VG, Kalluraya B (2006) Synth Com-
mun 36:1285
5. Chimenti F, Bolasco A, Manna F, Secci D, Chimenti P, Granese
A, Befani O, Turini P, Alcaro S, Ortuso F (2006) Chem Biol Drug
Des 67:206
6. Lin R, Chiu G, Yu Y, Connolly PJ, Li SJ, Lu YH, Adams M,
Fuentes-Pesquera AR, Emanuel SL, Greenberger LM (2007)
Bioorg Med Chem Lett 17:4557
17. Rai NS, Balakrishna Kalluraya B, Lingappa B, Shaliny Shenoy S,
Puranic VG (2008) Eur J Med Chem 43:1715
18. Al-Shiekh MA (2005) Org Prep Proced Int 37:223
123