Synthesis and X-ray structure characterisation of novel pyrazolecarboxamide derivatives

Article abstract of DOI:10.3184/174751913X13633729862156

A series of novel pyrazole carboxamide derivatives containing piperazine moiety was synthesised and determined by IR, ¹H NMR and HRMS spectroscopy. Especially, the structure was confirmed by the X-ray crystal analysis of [1-(4-tert-butylbenzyl)-4-chloro-3-(4-chlorophenyl)-1H-pyrazol-5-yl] (4-phenylpiperazin-1-yl)methanone.

Full text of DOI:10.3184/174751913X13633729862156

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 223
APRIL, 223–226
Synthesis and X-ray structure characterisation of novel pyrazole
carboxamide derivatives
Hong-Shui Lva, Xiao-Ling Dingb, Bao-Xiang Zhaoa*
aInstitute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. China
bCollege of Advanced ProfessionalTechnology, Qingdao University, Qingdao 266061, P. R. China
A series of novel pyrazole carboxamide derivatives containing piperazine moiety was synthesised and determined
1
by IR, H NMR and HRMS spectroscopy. Especially, the structure was confirmed by the X-ray crystal analysis of
[1-(4-tert-butylbenzyl)-4-chloro-3-(4-chlorophenyl)-1H-pyrazol-5-yl](4-phenylpiperazin-1-yl)methanone.
Keywords: pyrazole, piperazine, synthesis, X-ray structure
Pyrazoles are important nitrogen-containing heterocycles and
play a significant role in medicinal and pesticide chemistry
because of their excellent biological activities, including anal-
gesic1, anti-inflammatory,2,3 anti-angiogenic,4,5 anticancer,6–9
COX-2 inhibitors,10,11 antidepressant,12 anti-diabetic13 and anti-
microbial14–17. Much effort has been spent to synthesise novel
pyrazole derivatives which exhibit enhanced biological activi-
ties. One approach is to combine pyrazole with other active
molecules. Piperazine is the active group of some drugs such
piperaquine18 and ciprofloxacin.19 Therefore, many compounds
have been designed to connect the piperazine moiety to
improve their biological activities.20–22 Based on fragment
drug design principle, we now report the synthesis and X-ray
structure characterisation of pyrazole carboxamide derivatives
containing a piperazine moiety.
dihedral angle of 0.76(17)º. The orientations of the 4-tert-
butylphenyl moiety and piperazine moiety are defined by the
torsion angle of C(9)–N(2)–C(21)–C(22)56.2(4)º and N(2)–
C(9)–C(10)–N(3) –136.9(3)º, respectively. The tert-butyl
group exhibits rotational disorder between two orientations in
a 0.579:0.421 ratio. There are some intramolecular C–H…N,
C–H…O and C–H…Cl bonds giving rigidity to the molecule
(first three entries in Table 2). The packing of the molecules is
stabilised by intermolecular C–H…O and C–H…π hydrogen
bonds (last two entries in Table 2).
In conclusion, we have synthesised a series of novel pyr-
azole carboxamide derivatives containing piperazine moiety
by a relatively straight forward method. Structures of these
1
compounds were characterised by IR, H NMR and HRMS
spectroscopy. The molecular structure was confirmed by the
X-ray crystal analysis of compound (5i). Investigations are
underway to elucidate the bioactivity and the results will be
reported in due course.
Results and discussion
The synthesis of (4-chloro-1-arylmethyl-3-aryl-1H-pyrazol-5-yl)
(4-arylpiperazin-1-yl)methanone 5 was performed as outlined
in Scheme 1. The starting material ethyl 3-aryl-1H-pyrazole-5-
carboxylate 1 was synthesised as described in literature.23
Chlorination of 1 with N-chlorosuccinimide in CH3CN yielded
the chloropyrazole 2. The N-arylmethylation of 2 with substi-
tuted benzyl chloride in CH3CN at the presence of potassium
carbonate gave 3 in yield 32.6–74.0%. Pyrazole carboxylic
acids 4 were obtained by the alkali hydrolysis of pyrazole
esters 3. Pyrazole carboxylic acids first reacted with oxalyl
chloride in CH2Cl2 under reflux to give pyrazole carbonyl
chlorides. Then the target compounds 5 were obtained by the
reactions of pyrazole carbonyl chlorides with 1-arylpipera-
zines in the presence of triethylamine in CH2Cl2 at room
temperature in yields 44.8–82.9%.
Experimental
All reagents were of analytical grade or chemically pure. Analytical
TLC was performed on silica gel 60F254 plates (Merck KGaA).
Melting points were determined on an XD-4 digital micromelting
point apparatus. 1H NMR spectra were recorded on a Bruker Avance
400 spectrometer, using CDCl3 as solvent and TMS as internal stan-
dard. IR spectra were recorded with an IR spectrophotometer Avtar
370 FT-IR (Termo Nicolet). HRMS spectra were recorded on a LTQ
Orbitrap Hybrid mass spectrometer.
General procedure
A mixture of ethyl 3-aryl-1H-pyrazole-5-carboxylate 1 (15 mmol),
N-chlorosuccinimide (15.75 mmol) and CH3CN (50 mL) was refluxed
for 6 h. After cooling, the solvent was removed under reduced
pressure. The residue was washed with water and dried to give pure
compound 2. The N-arylmethylation of 2 was performed as described
in our previous paper24 to afford compounds 3. To a solution of 3
(10 mmol) in ethanol (50 mL) was added KOH (30 mmol). The
mixture was refluxed for 2 h. After cooling, ethanol was removed
under reduced pressure. The residue was dissolved in 50 mL water.
The solution was added hydrochloric acid (3 M) until pH = 4–5. The
precipitate was filtered and dried to give 4 as a pure product. A solu-
tion of 4 (1 mmol), oxalyl chloride (0.5 mL) and two drops of DMF in
CH2Cl2 (10 mL) was refluxed for 4 h. After cooling, the solvent was
removed. The residue was dissolved in CH2Cl2 (5 mL) and added
dropwise to a solution of 1-arylpiperazine in CH2Cl2 (10 mL) with
Et3N (0.5 mL) at room temperature. The mixture was stirred for 2–4 h.
The end of reaction was detected by TLC. Then the solution was
washed with water (20 mL × 2), the water phase was extracted with
CH2Cl2 (15 mL × 1). The combined organic phase was dried over
MgSO4. After filtration, the solvent was removed under reduced
pressure. The residue was purified by column chromatography on
silica gel using PE/EtOAc as an eluent to afford title compound 5 in
44.8–82.9%.
Structures of the compounds 5a–l were determined by IR,
1H NMR and HRMS spectroscopy. For example, IR spectrum
of compound 5c showed C=O stretching vibrations at 1638
1
cm−1. The H NMR spectral data of compound 5c showed
seven multiplet for protons of piperazine ring. The two protons
of CH2 connected with the pyrazole ring were observed a
double-doublet at δ 5.39–5.52. The two protons ortho to fluoro
group were observed as a triplet at 6.92–6.98 showing the 1H–
19F interaction in the phenyl ring. In the HRMS, in accordance
with the molecular structure of C31H33ClFN4O, compound 5c
gave a [M+H]-ion peak at m/z 531.2315.
The crystal structure of [1-(4-tert-butylbenzyl)-4-chloro-3-
(4-chlorophenyl)-1H-pyrazol-5-yl](4-phenylpiperazin-1-yl)
methanone (5i) is shown in Fig. 1. A summary of crystallo-
graphic data collection parameters and refinement parameters
are compiled in Table 1. The pyrazole ring makes a dihedral
angle of 12.29(15)º with the 4-chlorophenyl ring. The phenyl
ring and the 4-tert-butylphenyl ring are nearly parallel with a
[1-4-(tert-Butylbenzyl)-4-chloro-3-phenyl-1H-pyrazol-5-yl](4-
phenylpiperazin-1-yl)methanone (5a): White solid, yield: 44.8%; m.p.
173–174 °C; IR: νmax 1637 (C=O) cm−1; 1H NMR (CDCl3, 400 MHz):
* E-mail: bxzhao@sdu.edu.cn

224 JOURNAL OF CHEMICAL RESEARCH 2013
Scheme 1 Synthesis of compounds 5a–l. Reagents and conditions: (i) N-Chlorosuccinimide, CH3CN, reflux, 6 h; (ii) K2CO3, CH3CN,
reflux, 4 h; (iii) KOH/EtOH, reflux, 4 h, then HCl aq; (iv) (COCl)2, CH2Cl2, reflux, 3 h; (v) CH2Cl2, Et3N, 1-arylpiperazine, rt, 2–4 h.
Fig. 1 The molecule structure of compound 5i. Thermal ellipsoids for non-hydrogen atoms are drawn at the 30% probability
level.
δ = 1.13 (s, 9H, C(CH2)3), 2.05–2.14 (m, 1H, piperazine-H), 2.85–3.10
(m, 3H, piperazine-H), 3.20–3.30 (m, 1H, piperazine-H), 3.38–3.45
(m, 1H, piperazine-H), 3.55–3.60 (m, 1H, Piperazine–H), 3.98–4.03
(m, 1H, piperazine-H), 5.41 (d, 1H, J = 14.6 Hz, CH2), 5.50 (d, 1H,
J = 14.6 Hz, CH2), 6.81 (d, 2H, J = 8.0 Hz, ArH), 6.88 (t, 1H, J =
7.2 Hz, ArH), 7.18–7.33 (m, 6H, ArH), 7.39 (t, 1H, J = 7.2 Hz, ArH),
7.46 (t, 2H, J = 7.4 Hz, ArH), 7.92 (d, 2H, J = 8.0 Hz, ArH). HRMS
calcd for [M+H]+ C31H34ClN4O: 513.2421, found 513.2425.
400 MHz): δ = 1.16 (s, 9H, C(CH2)3), 1.95–2.08 (m, 1H, piperazine-H),
2.82–2.99 (m, 3H, piperazine-H), 3.05–3.15 (m, 1H, piperazine-H),
3.37–3.48 (m, 1H, piperazine-H), 3.62–3.71 (m, 1H, piperazine-
H), 3.92–4.03 (m, 1H, piperazine-H), 5.42 (d, 1H, J = 14.6 Hz, CH2),
5.50 (d, 1H, J = 14.6 Hz, CH2), 6.82 (t, 1H, J = 7.9 Hz, ArH), 6.92–
7.08 (m, 3H, ArH), 7.21 (d, 2H, J = 8.3 Hz, ArH), 7.31 (t, 2H, J =
8.3 Hz, ArH), 7.37–7.43 (m, 1H, ArH), 7.46 (t, 2H, J = 7.4 Hz, ArH),
7.92 (d, 2H, J = 7.3 Hz,ArH). HRMS calcd for [M+H]+ C31H33ClFN4O:
531.2327, found 531.2310.
[1-(4-tert-Butylbenzyl)-4-chloro-3-phenyl-1H-pyrazol-5-yl](4-
(2-fluorophenyl)piperazine-1-yl)methanone (5b): White solid, yield:
82.9%; m.p. 152–154 °C; IR: νmax 1637 (C=O) cm−1; 1H NMR (CDCl3,
[1-(4-(tert-Butylbenzyl)-4-chloro-3-phenyl-1H-pyrazol-5-yl](4-(4-
fluorophenyl)piperazin-1-yl)methanone (5c): White solid, yield:

JOURNAL OF CHEMICAL RESEARCH 2013 225
Table 1 Summary of crystal data and structure refinement
(m, 4H, piperazine-H), 3.50–4.09 (m, 3H, piperazine-H), 5.25–5.60
(m, 2H, CH2), 6.87–6.97 (m, 3H, ArH), 7.27–7.34 (m, 3H, ArH), 7.43
(d, 2H, J = 8.4 Hz, ArH), 7.67 (dd, 1H, J1 = 8.2 Hz, J2 = 2.0 Hz, ArH),
7.84 (d, 2H, J = 8.4 Hz, ArH), 8.38 (d, 1H, J = 2.0 Hz, ArH). HRMS
calcd for [M+H]+ C26H23Cl3N5O: 526.0968, found 526.0971.
{4-chloro-3-(4-chlorophenyl)-1-[(6-chloropyridin-3-yl)methyl]-
1H-pyrazol-5-yl}(4-(2-fluorophenyl)piperazin-1-yl)methanone (5f):
Yellow solid, yield: 65.7%; m.p. 157–159 °C; IR: νmax 1632 (C=O)
cm−1; 1H NMR (CDCl3, 400 MHz): δ = 1.94–2.09 (m, 1H, piperazine-H),
2.81–3.42 (m, 4H, piperazine-H), 3.55–3.80 (m, 2H, piperazine-H),
4.00–4.10 (m, 1H, piperazine-H), 5.35–5.62 (m, 2H, CH2), 6.89
(t, 1H, J = 8.1 Hz, ArH), 6.97–7.13 (m, 3H, ArH), 7.31 (d, 1H, J =
8.2 Hz, ArH), 7.43 (d, 2H, J = 8.6 Hz, ArH), 7.67 (dd, 1H, J1 = 8.2 Hz,
J2 = 2.3 Hz, ArH), 7.85 (d, 2H, J = 8.6 Hz, ArH), 8.39 (d, 1H, J =
2.3 Hz, ArH). HRMS calcd for [M+H]+ C26H22Cl3FN5O: 544.0874,
found 544.0882.
{4-Chloro-3-(4-chlorophenyl)-1-[(6-chloropyridin-3-yl)methyl]-
1H-pyrazol-5-yl}(4-(4-fluorophenyl)piperazin-1-yl)methanone (5g):
Yellow solid, yield: 74.5%; m.p. 144–147 °C; IR: νmax 1630 (C=O)
cm−1; 1H NMR (CDCl3, 400 MHz): δ = 1.95–2.05 (m, 1H, piperazine-H),
2.82–3.34 (m, 4H, piperazine-H), 3.50–3.80 (m, 2H, piperazine-H),
3.94–4.10 (m, 1H, piperazine-H), 5.35–5.60 (m, 2H, CH2), 6.85 (dd,
2H, J1 = 8.6 Hz, J2 = 4.5 Hz, ArH), 6.99 (t, 2H, J = 8.6 Hz, ArH), 7.29
(d, 1H, J = 8.2 Hz, ArH), 7.43 (d, 2H, J = 8.6 Hz, ArH), 7.67 (dd, 1H,
J1 = 8.2 Hz, J2 = 2.2 Hz, ArH), 7.84 (d, 2H, J = 8.6 Hz, ArH), 8.38 (d,
1H, J = 2.2 Hz, ArH). HRMS calcd for [M+H]+ C26H22Cl3FN5O:
544.0874, found 544.0864.
5i
Empirical formula
Formula weight
Temperature
C31H32Cl2N4O
547.51
293(2) K
Wavelength
0.71073 Å
Crystal system
space group
Unit cell dimensions
Monoclinic
P21/c
a = 15.107(7) Å,
α = 90°
b = 10.711(5) Å,
β = 92.499(8)°
c = 17.763(8) Å,
γ = 90°
Volume
2871(2) A3
Z
4
Calculated density
Absorption coefficient
Max. and min. transmission
F(000)
1.267 Mg m−3
0.257 mm−1
0.9748 and 0.9386
1152
0.25 × 0.10 × 0.10 mm
2.22 to 21.35°
–15≤h≤15,–10≤k≤10, –14≤l≤18
9734/3207 [R(int) = 0.0336]
Crystal size
θ range for data collection
Limiting indices
Reflections collected/unique
Completeness to theta = 25.05 99.6 %
Absorption correction
Refinement method
Multi-scan
Full-matrix least-squares on F2
3207/156/377
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I>2σ(I)]
R indices (all data)
{4-Chloro-3-(4-chlorophenyl)-1-[(6-chloropyridin-3-yl)methyl]-
1H-pyrazol-5-yl}(4-(3-methoxyphenyl)piperazin-1-yl)methanone
(5h): White solid, yield: 74.3%; m.p. 146–149 °C; IR: νmax 1639
1.015
R1 = 0.0400, wR2 = 0.0966
R1 = 0.0565, wR2 = 0.1077
0.255 and –0.179 e Å−3
1
(C=O) cm−1; H NMR (CDCl3, 400 MHz): δ = 2.52–2.60 (m, 1H,
Largest diff. peak and hole
piperazine-H), 3.03–3.31 (m, 4H, piperazine-H), 3.40–3.65 (m, 2H,
piperazine-H), 3.79 (s, 3H, OCH3), 3.88–4.00 (m, 1H, piperazine-H),
5.37–5.58 (m, 2H, CH2), 6.41–6.45 (m, 1H, ArH), 6.48–6.53 (m, 2H,
ArH), 7.20 (t, 1H, J = 8.2 Hz, ArH), 7.29 (d, 1H, J = 8.3 Hz, ArH),
7.42 (d, 2H, J = 8.4 Hz, ArH), 7.67 (dd, 1H, J1 = 8.3 Hz, J2 = 2.3 Hz,
ArH), 7.84 (d, 2H, J = 8.4 Hz, ArH), 8.38 (d, 1H, J = 2.3 Hz, ArH).
HRMS calcd for [M+H]+ C27H25Cl3N5O2: 556.1074, found 556.1074.
{1-[4-(tert-Butylbenzyl)-4-chloro-3-(4-chlorophenyl)-1H-pyrazol-
5-yl](4-phenylpiperazin-1-yl)methanone (5i): White solid, yield:
60.4%; m.p. 216–220 °C, IR: νmax 1633 (C=O) cm−1; 1H NMR (CDCl3,
400 MHz): δ = 1.13 (s, 9H, C(CH2)3), 2.05–2.15 (m, 1H, piperazine-H),
2.87–3.08 (m, 3H, piperazine-H), 3.20–3.30 (m, 1H, piperazine-H),
3.36–3.45 (m, 1H, piperazine-H), 3.55–3.66 (m, 1H, piperazine-
H), 3.95–4.05 (m, 1H, piperazine-H), 5.39 (d, 1H, J = 14.7 Hz, CH2),
5.49 (d, 1H, J = 14.7 Hz, CH2), 6.81 (d, 2H, J = 8.1 Hz, ArH), 6.89
(t, 1H, J = 7.3 Hz, ArH), 7.18–7.25 (m, 4H, ArH), 7.29 (d, 2H, J =
8.1 Hz, ArH), 7.43 (d, 2H, J = 8.4 Hz, ArH), 7.88 (d, 2H, J = 8.4 Hz,
ArH). HRMS calcd for [M+H]+ C31H33Cl2N4O: 547.2031, found
547.2026.
[1-(4-(tert-Butylbenzyl)-4-chloro-3-(4-chlorophenyl)-1H-pyrazol-
5-yl][4-(2-fluorophenyl)piperazin-1-yl]methanone (5j): White solid,
yield: 81.6%; m.p. 186–190 °C; IR: νmax 1633 (C=O) cm−1; 1H NMR
(CDCl3, 400 MHz): δ = 1.13 (s, 9H, C(CH2)3), 1.94–2.08 (m, 1H,
piperazine-H), 2.82–2.95 (m, 3H, piperazine-H), 3.05–3.15 (m, 1H,
piperazine-H), 3.35–3.46 (m, 1H, piperazine-H), 3.60–3.70 (m, 1H,
piperazine-H), 3.92–4.00 (m, 1H, piperazine-H), 5.40 (d, 1H, J = 14.6
Hz, CH2), 5.49 (d, 1H, J = 14.6 Hz, CH2), 6.81 (t, 1H, J = 8.0 Hz,
ArH), 6.91–7.08 (m, 3H, ArH), 7.20 (d, 2H, J = 8.2 Hz, ArH), 7.31 (d,
2H, J = 8.2 Hz, ArH), 7.43 (d, 2H, J = 8.5 Hz, ArH), 7.88 (d, 2H,
J = 8.5 Hz,ArH). HRMS calcd for [M+H]+ C31H32Cl2FN4O: 565.193;7,
found 565.1923.
[1-(4-(tert-Butylbenzyl)-4-chloro-3-(4-chlorophenyl)-1H-pyrazol-
5-yl][4-(4-fluorophenyl)piperazin-1-yl]methanone (5k): White solid,
yield: 68.7%; m.p. 226–229 °C, IR: νmax 1637 (C=O) cm−1; 1H NMR
(CDCl3, 400 MHz): δ = 1.13 (s, 9H, C(CH2)3), 1.98–2.05 (m, 1H,
piperazine-H), 2.75–2.86 (m, 1H, piperazine-H), 2.88–3.02 (m, 2H,
piperazine-H), 3.12–3.20 (m, 1H, piperazine-H), 3.35–3.45 (m, 1H,
piperazine-H), 3.52–3.61 (m, 1H, piperazine-H), 3.97–4.08 (m, 1H,
piperazine-H), 5.39 (d, 1H, J = 14.6 Hz, CH2), 5.49 (d, 1H, J =
14.6 Hz, CH2), 6.75 (dd, 2H, J1 = 8.8 Hz, J2 = 4.5 Hz, ArH), 6.94 (t,
2H, J = 8.8 Hz, ArH), 7.20 (d, 2H, J = 8.2 Hz, ArH), 7.28 (d, 2H,
J = 8.2 Hz, ArH), 7.43 (d, 2H, J = 8.4 Hz, ArH), 7.88 (d, 2H, J =
8.4 Hz, ArH). HRMS calcd for [M+H]+ C31H32Cl2FN4O: 565.1937,
found 565.1919.
Table 2 Hydrogen bond geometry (Å, °)
D–H…A
D–H
H…A
D…A
D–H…A
Intra C3–H3…Cl1
Intra C5–H5…N1
Intra C11–H11B…O1
C14–H14A…O1i
C6–H6…Cg5ii
0.93
0.93
0.97
0.97
0.93
2.65
2.50
2.36
2.40
2.74
3.340(4)
2.831(4)
2.768(4)
3.307(4)
3.578(4)
131
101
105
155
151
Symmetry code: (i) 1–x, –1/2+y, 3/2–z; (ii) 1–x, 1–y, 1–z.
D and A are the hydrogen-bond donor and acceptor, respect-
ively.
48.6%; m.p. 190–194 °C; IR: νmax 1638 (C=O) cm−1; 1H NMR (CDCl3,
400 MHz): δ = 1.13 (s, 9H, C(CH2)3), 1.92–2.03 (m, 1H, piperazine-H),
2.76–2.87 (m, 1H, piperazine-H), 2.90–3.03 (m, 2H, piperazine-H),
3.12–3.20 (m, 1H, piperazine-H), 3.37–3.48 (m, 1H, piperazine-
H), 3.53–3.62 (m, 1H, piperazine-H), 3.99–4.07 (m, 1H, piperazine-
H), 5.41 (q, 1H, J = 14.7 Hz, CH2), 5.50 (q, 1H, J = 14.7 Hz, CH2),
6.76 (dd, 2H, J1 = 8.9 Hz, J2 = 4.5 Hz, ArH), 6.94 (t, 2H, J = 8.9 Hz,
ArH), 7.21 (d, 2H, J = 8.2 Hz, ArH), 7.28 (d, 2H, J = 8.2 Hz, ArH),
7.37–7.43 (m, 1H, ArH), 7.47 (t, 2H, J = 7.5 Hz, ArH), 7.92 (d, 2H,
J = 7.3 Hz, ArH). HRMS calcd for [M+H]+ C31H33ClFN4O: 531.2327,
found 531.2315.
[1-(4-(tert-Butylbenzyl)-4-chloro-3-phenyl-1H-pyrazol-5-yl](4-(3-
methoxyphenyl)piperazin-1-yl)methanone (5d): White solid, yield:
51.0%; m.p. 159–161 °C; IR: νmax 1638 (C=O) cm−1; 1H NMR (CDCl3,
400 MHz): δ = 1.14 (s, 9H, C(CH2)3), 2.05–2.13 (m, 1H, piperazine-H),
2.85–3.08 (m, 3H, piperazine-H), 3.20–3.30 (m, 1H, piperazine-H),
3.34–3.46 (m, 1H, piperazine-H), 3.53–3.62 (m, 1H, piperazine-H),
3.77 (s, 3H, OCH3), 3.93–4.03 (m, 1H, piperazine-H), 5.41 (q, 1H,
J = 14.7 Hz, CH2), 5.50 (q, 1H, J = 14.7 Hz, CH2), 6.35 (s, 1H, ArH),
6.39–6.47 (m, 2H, ArH), 7.15 (t, 1H, J = 8.3 Hz, ArH), 7.21 (d, 2H,
J = 8.2 Hz, ArH), 7.28 (d, 2H, J = 8.2 Hz, ArH), 7.36–7.43 (m, 1H,
ArH), 7.46 (t, 2H, J = 7.5 Hz, ArH), 7.92 (d, 2H, J = 7.0 Hz, ArH).
HRMS calcd for [M+H]+ C32H36ClN4O2: 543.2527, found 543.2493.
{4-Chloro-3-(4-chlorophenyl)-1-[(6-chloropyridin-3-yl)methyl]-
1H-pyrazol-5-yl}(4-phenylpiperazin-1-yl)methanone (5e):Yellow solid,
yield: 54.6%; m.p. 154–157 °C; IR: νmax 1640 (C=O) cm−1; 1H NMR
(CDCl3, 400 MHz): δ = 2.44–2.60 (m, 1H, piperazine-H), 3.00–3.40

226 JOURNAL OF CHEMICAL RESEARCH 2013
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[1-(4-(tert-Butylbenzyl)-4-chloro-3-(4-chlorophenyl)-1H-pyrazol-
5-yl][4-(3-methoxyphenyl)piperazin-1-yl]methanone (5l): White solid,
yield: 56.0%; m.p. 163–166 °C; IR: νmax 1636 (C=O) cm−1; 1H NMR
(CDCl3, 400 MHz): δ = 1.14 (s, 9H, C(CH2)3), 2.04–2.13 (m, 1H,
piperazine-H), 2.85–3.08 (m, 3H, piperazine-H), 3.20–3.30 (m, 1H,
piperazine-H), 3.33–3.45 (m, 1H, piperazine-H), 3.52–3.63 (m,
1H, piperazine-H), 3.77 (s, 3H, OCH3), 3.94–4.01 (m, 1H, piperazine-
H), 5.39 (d, 1H, J = 14.6 Hz, CH2), 5.49 (d, 1H, J = 14.6 Hz, CH2),
6.32–6.35 (m, 1H, ArH), 6.38–6.46 (m, 2H, ArH), 7.14 (t, 1H, J =
8.1 Hz, ArH), 7.20 (d, 2H, J = 8.3 Hz, ArH), 7.29 (d, 2H, J = 8.3 Hz,
ArH), 7.43 (d, 2H, J = 8.6 Hz, ArH), 7.88 (d, 2H, J = 8.6 Hz, ArH).
HRMS calcd for [M+H]+ C32H35Cl2N4O2: 577.2137, found 577.2145.
Crystal structure determination of [1-(4-(tert-butylbenzyl)-4-
chloro-3-(4-chlorophenyl)-1H-pyrazol-5-yl](4-phenylpiperazin-1-
yl)methanone (5i): Suitable single crystals of 5i for X-ray structural
analysis were obtained by recrystallisation from ethyl acetate. The dif-
fraction data was collected with a Bruker SMART CCD diffractome-
ter using a graphite monochromated Mo Kα radiation (λ = 0.71073 Å)
at 293(2) K. The structures were solved by direct methods with
SHELXS-97 program and refinements on F2 were performed with
SHELXL-9725 program by full-matrix least-squares techniques
with anisotropic thermal parameters for the nonhydrogen atoms. All H
atoms were initially located in a difference Fourier map. The methyl
H atoms were then constrained to an ideal geometry, with C–H =
0.96 Å and Uiso(H) = 1.5 Ueq(C). All other H atoms were placed in
geometrically idealised positions and constrained to ride on their
parent atoms, with C–H = 0.93 Å and Uiso(H) = 1.2 Ueq(C). The
information of CCDC [917577] can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk.
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This work was supported the Independent Innovation Founda-
tion of Shandong University (2009JC007).
Received 8 January 2013; accepted 4 February 2013
Paper 1301713 doi: 10.3184/174751913X13633729862156
Published online: 19 April 2013
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