Synthesis, crystal structures and DFT studies of 1-[2-(5-methyl-2- benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3,4-dimethoxyphenyl)-4, 5-dihydro-1H-pyrazole and 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3- phenyl-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole

Article abstract of DOI:10.1016/j.molstruc.2011.08.061

The title compounds, 1-[2-(5-methyl-2-benzoxazolinone-3-yl)acetyl]-3- phenyl-5-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole (5a) and 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(4-methoxyphenyl)-4, 5-dihydro-1H-pyrazole (5b), were synthesized. The crystal and molecular structures of 5a and 5b have been determined by elemental analyses, IR, ¹H NMR, ESI-MS and single-crystal X-ray diffraction. Molecular geometries of 5a and 5b in the ground state have been calculated using the density functional method (DFT) with B3LYP/6-31G(d,p) basis set and compared with the experimental data. In addition, the molecular electrostatic potential maps and frontier molecular orbitals of 5a and 5b were performed.

Full text of DOI:10.1016/j.molstruc.2011.08.061

Journal of Molecular Structure 1006 (2011) 147–158
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis, crystal structures and DFT studies of 1-[2-(5-methyl-2-benzoxazolinone-
3-yl)acetyl]-3-phenyl-5-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole and
1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-
5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole
b
b
a
Zarife Sibel Sßahin a, , Umut Salgın-Göksßen , Nesrin Gökhan-Kelekçi , Sßamil Ißsık
⇑
a Ondokuz Mayis University, Faculty of Arts and Sciences, Department of Physics, 55139 Kurupelit, Samsun, Turkey
b Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 06100 Sıhhiye, Ankara, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 June 2011
Received in revised form 30 August 2011
Accepted 30 August 2011
Available online 10 September 2011
The title compounds, 1-[2-(5-methyl-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3,4-dimethoxyphenyl)-
4,5-dihydro-1H-pyrazole (5a) and 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(4-methoxy-
phenyl)-4,5-dihydro-1H-pyrazole (5b), were synthesized. The crystal and molecular structures of 5a and
5b have been determined by elemental analyses, IR, 1H NMR, ESI-MS and single-crystal X-ray diffraction.
Molecular geometries of 5a and 5b in the ground state have been calculated using the density func-
tional method (DFT) with B3LYP/6-31G(d,p) basis set and compared with the experimental data. In
addition, the molecular electrostatic potential maps and frontier molecular orbitals of 5a and 5b were
performed.
Keywords:
2-Pyrazoline
Crystal structure
DFT calculations
Molecular electrostatic potential
Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction
has been very popular for calculations in theoretical modeling
since the 1970s. In many cases the results of DFT calculations for
Oxazolone and pyrazoline derivatives are in general well-known
five-membered nitrogen-containing heterocyclic compounds [1].
Several pyrazoline derivatives have been found to possess consider-
able biological activities which stimulated research activities in this
field [2–6]. They exhibit a plethora of bioactivities viz, COX-2 inhib-
itor [7], anti-inflammatory and analgesic [4,8–12], antibacterial,
antifungal [13], antitumor [14], anticancer [15–17], antidepressant
[18–20], antinociceptive [21,22]. As far as the different pyrazoline
isomers are concerned, 2-pyrazoline derivatives became the most
frequently studied pyrazolines. 2-Pyrazolines are also used in the
treatment of Parkinson’s, Alzehimer’s disease and Cerebral edema
[23,24].
On the other hand, oxazolone derivatives are highly versatile
intermediates used for the synthesis of several organic molecules,
including amino acids, peptides, antimicrobial or antitumor com-
pounds, monoamine oxidase inhibitors, immunomodulators, het-
erocyclic precursors for biosensors coupling, and photosensitive
composition devices for proteins [25–30].
solid-state systems agreed quite satisfactorily with experimental
data. DFT predicts a great variety of molecular properties: molecu-
lar structures, vibrational frequencies, atomization energies, ioni-
zation energies, electric and magnetic properties, reaction paths,
etc.
In view of these observations, herein we report the synthesis of
two new 2-pyrazolines by using the chalcones and hydrazine deriv-
atives. Chemical structures of compounds were confirmed by IR, 1H
NMR, elementary analysis, ESI-MS and X-ray single-crystal determi-
nation. The geometrical parameters, fundamental frequencies and
GIAO 1H chemical shift values of the title compounds in the ground
state were calculated using the DFT method (B3LYP) with 6-
31G(d,p) basis set. Besides, molecular electrostatic potentials
(MEP) and frontier molecular orbitals (FMO) were performed.
2. Experimental and computational method
2.1. Chemistry
Many important chemical and physical properties of the chem-
ical systems can be predicted from first principles by various
computational techniques [31]. Density functional theory (DFT)
All chemicals and solvents used in the present study were pur-
chased from Merck A.G., Aldrich Chemical. Melting point of the
compounds were determined by using a Thomas Hoover Capillary
Melting Point Apparatus and were uncorrected. Infrared (IR) spec-
tra were obtained with a Bruker Vector 22 IR (Opus Spectroscopic
⇑
Corresponding author. Tel.: +90 3623121919.
E-mail address: sgul@omu.edu.tr (Z.S. Sßahin).
0022-2860/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2011.08.061

148
Z.S. Sßahin et al. / Journal of Molecular Structure 1006 (2011) 147–158
Software Version 2.0) spectrometer using potassium bromide
plates and the results were expressed in wave number (cmꢀ1).
1H NMR spectrums were recorded on a Bruker AC 400 MHz spec-
trometer using dimethylsulfoxide with chemical shifts being re-
ported as d (ppm) from TMS. Mass spectrums were undertaken
using Waters 2695 Alliance Micromass ZQ LC/MS in methanol
according to the EI technique. Elemental analyses (C, H, N) were
performed on Leco CHNS 932 analyzer in the laboratory of the An-
kara University. The purity of the compounds were assessed by TLC
on silicagel HF254+366 (E.Merck, Darmstadt, Germany).
one of the most rapid and efficient methods for obtaining both
enantiomers of a chiral compound in high optical purity in a single
operation [38]. However, we are unable to separate the enantio-
mers of compounds due to the restricted facilities.
2.2.1. General procedure for the preparation of 1,3-diaryl-2-propen-1-
ones 4 (chalcones)
Chalcone derivatives were synthesized by condensing aceto-
phenone (10 mmol) and appropriate benzaldehydes (10 mmol)
with the presence of a solution of sodium hydroxide (12.5 mmol)
in 5 mL of water–3 mL of ethanol at 0 °C for 1 h. The solid mass
separated out was filtered, dried and crystallized from methanol
[36].
5-Methyl-2-benzoxazolinone 1, ethyl 2-(5-methyl/chloro
-2-benzoxazolinone-3-yl)acetate 2a–2b and 2-(5-methyl/chloro-
2-benzoxazolinone-3-yl)acetylhydrazine 3a–3b were synthesized
according to the literature published before [32–35].
1-Phenyl-3-(3,4-dimethoxyphenyl)-2-propen-1-one
(4a).
88.2%; m.p.: 86.5–88.5 °C [39].
1-Phenyl-3-(4-methoxyphenyl)-2-propen-1-one (4b). 96.9%;
2.2. Synthesis
m.p.: 75–76 °C [40].
The synthesis pathway leading to the title compound is given
in Scheme 1. 5-Methyl-2-benzoxazolinone 1, was synthesized
according to the literature method using 4-methyl-2-aminophe-
nol and urea [32]. Treatment of 5-methyl/chloro-2-benz-
oxazolinone with ethyl chloroacetate in K2CO3/acetone gave the
N-alkylated product ethyl (5-methyl/chloro-2-benzoxazolinone-
3-yl)acetate 2a–2b [33]. The acid hydrazides 3a–3b were
prepared by the reaction of ethyl (5-methyl/chloro2-benzoxazoli-
none-3-yl)acetate and hydrazine hydrate in ethanol [34,35]. On
2.2.2. General procedure for the preparation of 1-[2-(5-substituted-2-
benzoxazolinone-3-yl)acetyl]-3,5-diaryl-4,5-dihydro-1H-pyrazoles (5)
2-(5-Methyl/Chloro-2-benzoxazolinone-3-yl)acetylhydrazine
(1 mmol) was dissolved in 2 mL of DMF and 20 mL of n-propa-
nol. 1-Phenyl-3-(3,4-dimethoxy/4-methoxyphenyl)-2-propen-1-
one (1 mmol) and eight drops of hydrochloric acid was added
to this solution and was refluxed for approximately 120 h [41].
The reaction mixture was then cooled and the solid precipitated
was recrystallized. If solid was not precipitated, the solution was
purified by chromatography on a silica gel column.
the other hand,
a,b-unsaturated carbonyl compounds (chalcones)
4a–4b was prepared by reacting appropriate aldehydes and ace-
tophenone derivatives under basic condition according to the
Claisen–Schmidt condensation [36]. The reaction of hydrazides
3a–3b with chalcones 4a–4b in n-propanol under acidic condi-
tion gave compounds 1-[2-(5-methyl/chloro-2-benzoxazolinone-
3-yl)acetyl]-3,5-diaryl-4,5-dihydro-1H-pyrazoles 5a–5b.
The purity of the synthesized compounds were checked by ele-
mental analyses. The structures of the synthesized compounds
were determined on the basis of spectral data analysis; such as
IR, 1H NMR and ESI-MS.
2.2.3. 1-[2-(5-Methyl-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-
(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole (5a)
Derivative 5a was obtained by the reaction of 3a with 4a. The
solid precipitated was recrystallized from acetone–water (3:1) to
give 49.8% of 5a as a cream crystal. M.p.: 175–176 °C. IR (KBr)
cmꢀ1: 2942 (CAH), 1768, 1673 (C@O), 1627, 1607, 1516, 1499,
1455(C@C, C@N); 1H NMR (400 mHz, DMSO-d6) d (ppm): 2.29 (s,
3H, ACH3), 3.23 (dd; 1H; HA, JAB: 18.2 Hz, JAX: 4.8 Hz), 3.71 (s, 3H,
There is a chiral center at the C5 position of the pyrazole moiety
of the compounds. It is known that stereochemistry may be an
important modulator of biological activity [37]. Chiral HPLC is
phenyl-OCH3), 3.72 (s, 3H, phenyl-OCH3), 3.90 (dd; 1H; HB, JAB
18.2 Hz, JBX: 11.4 Hz), 5.04 (d; H; NACH1H2ACO, J: 18.0 Hz), 5.21
(d; H; NACH1H2ACO, J: 17.6 Hz), 5.54 (dd; HX; JAX: 4.8 Hz, JBX
:
:
Scheme 1. Synthesis of the title compounds.

Z.S. Sßahin et al. / Journal of Molecular Structure 1006 (2011) 147–158
149
Table 1
Parameters for data collection and structure refinement of 5a and 5b.
Crystal data
5a
27H25N3O5
Prism, colorless
471.50
5b
Chemical formula
Crystal shape/color
Formula weight
Crystal system
C
C25H20ClN3O4
Prism, colorless
461.89
Orthorhombic
Monoclinic
Space group
Unit cell parameters
P212121
P21/c
0
0
a = 8.3170 (3) ÅA
a = 5.995 (5) ÅA
0
0
b = 13.6675 (8) ÅA
b = 22.885 (6) ÅA
0
0
c = 21.0259 (9) ÅA
c = 16.079 (5) ÅA
b = 94.705 (5)°
Temperature (K)
Volume
296
296
2199 (2) ÅA3
0
0
2390.07 (19) ÅA3
Z
4
4
Dx (Mg mꢀ3
)
1.310
0.09
992
1.395
0.21
960
l
(mmꢀ1
F000
)
Crystal size (mm)
Data collection
0.44 ꢁ 0.39 ꢁ 0.20
0.22 ꢁ 0.13 ꢁ 0.07
Diffractometer/meas.meth
Absorption correction
Tmin
STOE IPDS II/w-scan
Integration
0.991
STOE IPDS II/w-scan
Integration
0.989
Tmax
0.996
0.997
No. of measured, independent and observed reflections
2676, 1826, 1527
15555, 4326, 2341
Criterion for observed reflection
I > 2
r(I)
I > 2r(I)
Rint
hmax (°)
0.067
26.0
0.071
26.0
Refinement
Refinement on
F2
F2
R[F2 > 2
r
(F2)], wR(F2), S
0.044, 0.135, 1.00
0.058, 0.106, 0.98
No. of reflections
No. of parameters
2676
319
4326
299
2
2
w ¼ 1=½r2ðF20Þ þ ð0:0643PÞ ꢂ; P ¼ ðF02 þ 2F2CÞ=3
w ¼ 1=½r2ðF20Þ þ ð0:0361PÞ ꢂ; P ¼ ðF02 þ 2F2CÞ=3
Weighting scheme
0
0.14, ꢀ0.13
0.15, ꢀ0.21
D
qmax
,
D
qmin (e ÅAꢀ3
)
11.4 Hz), 6.73–6.93 (m, 4H, 2-benzox.-H6 ve phenyl-3H), 7.07 (s,
1H, 2-benzox.-H4), 7.21 (d, 1H, 2-benzox.-H7, J67 8.4 Hz),
7.49–7.52 (m, 3H, phenyl-3H), 7.85–7.87 (m, 2H, phenyl-2H);
ESI-MS: m/z (%): 510 ([M+K]+, 10%), 495 ([M+Na+H]+, 31%), 494
([M+Na]+, 100%), 472 ([M+H]+, 3%). Calculated for C27H25N3O5: C,
68.78; H, 5.34; N, 8.91. Found: C, 68.40; H, 5.314; N, 8.842.
structures were solved by direct-methods using SHELXS-97 [42]
and refined by full-matrix least-squares methods on F2 using SHEL-
XL-97 [42] from within the WINGX [43,44] suite of software. The
parameters for data collection and structure refinement of com-
plexes 5a and 5b are listed in Table 1. In complex 5a, in the absence
of significant anomalous scattering effects, Friedel pairs were
merged. All non-hydrogen atoms were refined with anisotropic
parameters. Hydrogen atoms bonded0 to carbon were placed in cal-
culated positions (CAH = 0.93–0.97 ÅA) and treated using a riding
model with U = 1.2 times the U value of the parent atom for CH,
CH2 and CH3. Molecular diagrams were created using ORTEP-III
[45]. Geometric calculations were performed with PLATON [46].
Details of hydrogen-bond dimensions are given in Table 3.
:
2.2.4. 1-[2-(5-Chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(4-
methoxyphenyl)-4,5-dihydro-1H-pyrazole (5b)
Derivative 5b was obtained by the reaction of 3b with 4b. Then
the reaction mixture was cooled and the solvent was concentrated
under reduced pressure. The residue was purified by chromatogra-
phy on a silica gel column by using n-hexane/ethyl acetate. The
solid precipitated was recrystallized from acetone–water (3:1) to
give 6.2% of 5b as a cream crystal. M.p.: 190–191 °C. IR (KBr)
cmꢀ1: 3066 (CAH), 1789, 1678 (C@O), 1606, 1512, 1488, 1441
(C@C, C@N); 1H NMR (400 mHz, DMSO-d6) d (ppm): 3.22 (dd;
1H; HA, JAB: 18.4 Hz, JAX: 4.8 Hz), 3.72 (s, 3H, phenyl-OCH3), 3.90
(dd; 1H; HB, JAB: 18.2 Hz, JBX: 11.6 Hz), 5.08 (d; H; NACH1H2ACO,
J: 17.6 Hz), 5.22 (d; H; NACH1H2ACO, J: 17.6 Hz), 5.54 (dd; HX;
JAX: 4.8 Hz, JBX: 11.6 Hz), 6.88 (d, 2H, phenyl-2H, J: 8.8 Hz),
7.16–7.19 (m, 3H, phenyl-3H), 7.39 (d, 1H, phenyl-H, J: 8.8 Hz),
7.48–7.52 (m, 4H, phenyl-4H), 7.85–7.88 (m, 2H, phenyl-2H);
ESI-MS: m/z (%): 510 ([M+K]+, 10%), 465 ([M+Na+H]+, 31%), 464
([M+Na]+, 100%), 462 ([M+H]+, 3%). Calculated for C25H20ClN3O4:
C, 65.01; H, 4.36; N, 9.10. Found: C, 64.67; H, 4.809; N, 8.606.
2.4. Theoretical methods
The compounds 5a and 5b were optimized by using DFT method.
The initial guess of the compounds was first obtained from the
X-ray coordinates. DFT calculations with a hybrid functional
B3LYP (Becke’s three parameter hybrid functional using the LYP
correlation functional) at 6-31G(d,p) basis set using the Berny
method [47,48] were performed with the Gaussian 03 software
package [49], and Gauss-view visualization program [50]. To inves-
tigate the reactive sites of the compounds 5a and 5b, the molecular
electrostatic potentials were calculated using the same method.
The calculation of harmonic vibrational frequencies for the opti-
mized geometries were made at the same level and these were
scaled by 0.9627 [51]. The geometries of the title compounds, to-
gether with that of tetramethylsilane (TMS) were fully optimized.
1H NMR chemical shifts were calculated using the standard
GIAO/B3LYP/6-31G(d,p) (gauge-independent atomic orbital) ap-
proach [52,53]. The 1H NMR chemical shifts were converted to
2.3. Crystallography
Colorless single-crystals of 5a and 5b suitable for data collection
were selected and performed on a STOE IPDS II diffractometer with
0
graphite monochromated MoKa radiation k = 0.71073 ÅA. The

150
Z.S. Sßahin et al. / Journal of Molecular Structure 1006 (2011) 147–158
Fig. 1. The molecular structure of 5a, shown with 30% probability displacement ellipsoids and illustrating the atom-numbering scheme.
the TMS scale by subtracting the calculated absolute chemical
shielding of TMS (d = R0 , where d is the chemical shift, is
the absolute shielding and R0 is the absolute shielding of TMS),
planar, the maximum deviations from the least-squares planes
0 0
being 0.0065(27) ÅA for atom N3 in 5a, 0.0525(19) ÅA for atom C12
ꢀ
R
R
in 5b. The benzoxazole rings are almost planar, the maximum devi-
0
with values of 32.01 ppm for B3LYP/6-31G(d,p).
ations from the least-squares planes being 0.0291(41) ÅA for atom
0
C6 in 5a, 0.0152(22) ÅA for atom C27 in 5b, with dihedral angles
of 1.43(3)° for 5a and 0.31(2)° for 5b, respectively, between the
3. Results and discussion
Table 2
3.1. Supramolecular structures
Selected bond lengths, angles and dihedral angles (Å, °).
The molecular structures of the 5a and 5b determined by X-ray
crystallography have been depicted in Figs. 1 and 5, respectively.
Each compounds, contain a phenyl ring (C13AC18) and a methoxy-
phenyl group (C19AC24) attached to the central pyrazole ring
(N2/N3/C10AC12). The bond lengths in the pyrazole ring show
(5a)
(5b)
X-ray
B3LYP/6-
31G(d,p)
X-ray
B3LYP/6-
31G(d,p)
Bond lengths
N2AN3
1.402 (5) 1.377
1.291 (5) 1.293
1.503(7)
1.534(6)
1.513(6)
1.463(7)
1.219 (5) 1.221
1.178 (6) 1.206
1.447 (5) 1.488
1.357 (5) 1.372
1.454 (6) 1.441
1.369 (6) 1.387
1.393 (6) 1.394
1.394 (3) 1.377
1.285 (3) 1.293
1.504(4)
1.544(4)
1.508(4)
1.465(4)
1.215 (3) 1.221
1.195 (3) 1.204
1.483 (3) 1.487
1.347 (4) 1.369
1.447 (4) 1.390
1.361 (4) 1.389
1.386 (3) 1.390
N3AC10
C10AC11
C11AC12
C12AC19
C10AC13
C9AO3
C27AO2
N2AC12
N2AC9
partial aromatic character, which suggests a delocalized p-electron
1.519
1.554
1.516
1.466
1.518
1.555
1.516
1.465
system throughout the ring. It is likely that the two substituent
groups at the 3- and 5-positions of the pyrazole ring influence
the aromaticity of that ring. The presence of a C9AO3 bond at
the 1-position results in a lengthening of the N2AN3 bonds. The
0
0
N3AC10 bond lengths of 1.291(5) ÅA for 5a and 1.285(3) ÅA for 5b
are indicative of significant double-bond character. The N2AC12
and N2AC9 bond distances (Table 2) deviate significantly from
the mean value of NAC distances in pyrazole rings [54–56]. The
phenyl and methoxyphenyl rings are oriented at angles of
2.07(3)° and 72.40(2)° for 5a, and 3.93(2)° and 87.93(1)° for 5b,
respectively, to the pyrazole ring. The dihedral angles between
the phenyl and methoxyphenyl rings are 74.34(2)° for 0 5a and
N1AC8
N1AC27
N1AC6
Bond angles
N2AC12AC19 114.6 (4) 112.6
N3AC10AC13 120.8 (5) 121.9
112.1 (2) 112.8
121.7 (3) 122.0
Dihedral angles
86.51(1)° for 5b. The C27AO2 bond lengths of 1.178(6) ÅA for 5a
0
A/B
A/C
B/C
72.40
81.29
80.12
88.44
69.99
70.28
87.93
75.34
75.05
86.10
77.63
73.69
and 1.195(3) ÅA for 5b are indicative of significant double-bond
character. The bond lengths observed in 5a and 5b have normal
values, and both the bond lengths and angles are comparable to
those observed in related structure [57]. The pyrazole rings are
(A: pyrazole ring, B: methoxyphenyl ring and C: benzoxazole ring).

Z.S. Sßahin et al. / Journal of Molecular Structure 1006 (2011) 147–158
151
Table 3
0
Hydrogen-bond parameters (AÅ,ꢀ).
D–Hꢃ ꢃ ꢃA
D–H
Hꢃ ꢃ ꢃA
Dꢃ ꢃ ꢃA
D–Hꢃ ꢃ ꢃA
Chain
Motif
Direction
5a
C7AH7ꢃ ꢃ ꢃO2i
0.93
0.97
2.64
2.50
3.509(7)
3.398(7)
155
153
C(6)
C(5)
[100]
[100]
R12ð7Þ
C8AH8Aꢃ ꢃ ꢃO2i
R12ð7Þ
C15AH15ꢃ ꢃ ꢃO3ii
0.93
0.98
2.64
2.77
3.345(6)
3.556(5)
133
138
C(9)
C(7)
–
–
[001]
[100]
C12AH12ꢃ ꢃ ꢃCg1iii
5b
C11AH11Bꢃ ꢃ ꢃO2iv
C11AH11Aꢃ ꢃ ꢃO1v
C24AH24ꢃ ꢃ ꢃO3vi
C4AH4ꢃ ꢃ ꢃCg5vii
0.97
0.97
0.93
0.93
2.42
2.66
2.44
2.92
3.160(4)
3.567(4)
3.298(4)
3.847(5)
133
155
153
177
C(9)
C(9)
C(7)
C(11)
–
–
–
[001]
[101]
[100]
[101]
R22ð20Þ
C17AH17ꢃ ꢃ ꢃCg5viii
C25AH25Cꢃ ꢃ ꢃCg4ix
0.93
0.96
3.13
2.83
3.913(5)
3.619(5)
142
140
C(9)
[101]
[001]
R22ð20Þ
C(12)
–
Cg1 = O1AN1AC5AC6AC27; Cg4 = C13AC14AC15AC16AC17AC18; Cg5 = C19AC20AC21AC22AC23AC24. Symmetry codes: (i) x + 1/2, ꢀy + 1/2, ꢀz + 1; (ii) ꢀx + 1/2, ꢀy + 1,
z + 1/2; (iii) x ꢀ 1/2, ꢀy + 1/2, 1 ꢀ z; (iv) x, ꢀy + 1/2, z ꢀ 1/2; (v) x ꢀ 1, ꢀy + 1/2, zꢀ1/2; (vi) x ꢀ 1, y, z; (vii) x + 1, 1/2 ꢀ y, 1/2 + z; (viii) x ꢀ 1, 1/2 ꢀ y, z ꢀ 1/2; (ix) x, 1/2 ꢀ y, 1/
2 + z.
five- and six-membered rings. The dihedral angles between benz-
oxazole and pyrazole rings are 80.68(2)° for 5a and 75.35(2)° for
5b.
3.1.1. Compound (5a)
The compound of 1-[2-(5-methyl-2-benzoxazolinone-3-yl)a-
cetyl]-3-phenyl-5-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyra-
zole (5a) (Fig. 1) crystallizes in the space group P212121, and
the molecules are linked into sheets by a combination of three
CAHꢃ ꢃ ꢃO hydrogen bonds and one CAHꢃ ꢃ ꢃ
p hydrogen bond
(Table 3), and these sheets are linked into a two-dimensional
framework structure by a combination of two aromatic
stacking interactions.
pꢃ ꢃ ꢃp
In the simplest of the two sub-structures, atom C7 in the refer-
ence molecule at (x, y, z) acts as a hydrogen-bond donor, via H7, to
atom O2 in the molecule at (x + 1/2, ꢀy + 1/2, ꢀz + 1), so forming a
C(6) [58] chain running parallel to the [100] direction. Similarly,
atom C8 in the molecule at (x, y, z) acts as a hydrogen-bond donor,
via H8A, to atom O2 in the molecule at (x + 1/2, ꢀy + 1/2, ꢀz + 1),
so forming a C(5) chain running parallel to the [100] direction. The
combination of the C(5) and C(6) chains generates a chain of edge-
fused R12ð7Þ rings running parallel to the [100] direction (Fig. 2).
In the final sub-structure, atom C15 in the reference molecule at
(x, y, z) acts as a hydrogen-bond donor, via H15, to atom O3 in the
molecule at (ꢀx + 1/2, ꢀy + 1, z + 1/2), so forming a C(9) chain run-
ning parallel to the [001] direction (Fig. 3).
Fig. 2. Part of the crystal structure of 5a showing the formation of a chain edge-
fused R12ð7Þ rings along [100]. Hydrogen atoms have been omitted for clarity.
pyrazole (Cg2) ring in the molecule at (x, y, z) makes dihedral an-
gles of only 1.3(3)° and 0.6(3)° with the oxazolidinone (Cg1) ring
in the molecule at (x ꢀ 1/2, ꢀy + 1/2, 1 ꢀ z) and the phenyl (Cg3)
ring in the molecule at (x ꢀ 1/2, ꢀy + 1/2, 1 ꢀ z). Details of these
interactions are given in Table 4. Propagation by translation of this
stacking interactions then generates a
parallel to the [100] direction (Fig. 4).
p-stacked chain running
The C12 atom in the molecule at (x, y, z) acts as a hydrogen-
bond donor to the oxazolidinone (Cg1) ring in the molecule at
(x ꢀ 1/2, ꢀy + 1/2, 1 ꢀ z), so forming a C(7) chain running parallel
to the [100] direction (Fig. 4). The combination of the CAHꢃ ꢃ ꢃO
3.1.2. Compound (5b)
The compound of 1-[2-(5-chloro-2-benzoxazolinone-3-yl)ace-
tyl]-3-phenyl-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole (5b)
and CAHꢃ ꢃ ꢃ
p
hydrogen bonds define an R22ð12Þ ring pattern.
Compound 5a also contains two
pꢃ ꢃ ꢃ
p
stacking interactions. The
Fig. 3. Part of the crystal structure of 5a showing the formation of a chain along [001] generated by CAHꢃ ꢃ ꢃO hydrogen bonds. Hydrogen atoms have been omitted for clarity.

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Z.S. Sßahin et al. / Journal of Molecular Structure 1006 (2011) 147–158
Fig. 4. Part of the crystal structure of 5a showing the formation of a chain along [100] generated by the CAHꢃ ꢃ ꢃ
p
hydrogen bonds and
pꢃ ꢃ ꢃp
stacking interactions. Hydrogen
atoms have been omitted for clarity.
Table 4
pꢃ ꢃ ꢃp interactions parameters.
0
0
Cg(I)
Cg(J)
Cgꢃ ꢃ ꢃCg (AÅ)
Perpendicular distance (ÅA)
5a
Cg2
Cg2
Cg1iii
Cg3iii
3.788(3)
3.653(3)
3.540(2)
3.535(2)
5b
Cg6
Cg4
Cg6x
Cg7vi
3.968(4)
3.865(4)
3.335
3.758
Cg2 = N2AN3AC10AC11AC12; Cg3 = C2AC3AC4AC5AC6AC7; Cg6 = C2AC3AC4AC5AC6AC7;
Cg7 = N2AN3AC10AC11AC12. Symmetry code: (x) 2 ꢀ x, ꢀy, 2 ꢀ z.
Fig. 5. The molecular structure of 5b, shown with 30% probability displacement ellipsoids and illustrating the atom-numbering scheme.

Z.S. Sßahin et al. / Journal of Molecular Structure 1006 (2011) 147–158
153
Fig. 6. Part of the crystal structure of 5b showing the formation of a chain along [101] generated by the CAHꢃ ꢃ ꢃO hydrogen bonds. Hydrogen atoms have been omitted for
clarity.
Fig. 7. Part of the crystal structure of 5b showing the formation of a chain along [001] generated by the CAHꢃ ꢃ ꢃO hydrogen bonds. Hydrogen atoms have been omitted for
clarity.
(Fig. 5) crystallizes in the space group P21/c, and the molecules are
y, z) acts as a hydrogen-bond donor to the phenyl (Cg4) ring in
the molecule at (x, 1/2 ꢀ y, 1/2 + z), so forming a C(12) chain run-
ning parallel to the [001] direction. The second is the C17 atom
in the molecule at (x, y, z) acts as a hydrogen-bond donor to the
phenyl (Cg5) ring in the molecule at (x ꢀ 1, 1/2 ꢀ y, z ꢀ 1/2), so
forming a C(9) chain running parallel to the [101] direction. Final-
ly, C4 atom in the molecule at (x, y, z) acts as a hydrogen-bond do-
nor to the phenyl (Cg5) ring in the molecule at (x + 1, 1/2 ꢀ y, 1/
2 + z), so forming a C(11) chain running parallel to the [100]
direction. The combination of the C(9) and C(11) chains generates
a chain of edge-fused R22ð20Þ rings running parallel to the [101]
direction (Fig. 9).
linked into sheets by a combination of three CAHꢃ ꢃ ꢃO hydrogen
bonds and three CAHꢃ ꢃ ꢃ
p hydrogen bond (Table 3), and these sheets
are linked into a two-dimensional framework structure by a combi-
nation of two aromatic stacking interactions.
p
ꢃ ꢃ ꢃ
p
Atom C11 in the reference molecule at (x, y, z) acts as a hydro-
gen-bond donor, via H11B, to atom O2 in the molecule at (x, ꢀy + 1/
2, zꢀ1/2), so forming a C(9) chain running parallel to the [001]
direction (Fig. 6). Atom C11 in the molecule at (x, y, z) acts as a
hydrogen-bond donor, via H11A, to atom O1 in the molecule at
(x ꢀ 1, ꢀy + 1/2, z ꢀ 1/2), so forming a C(9) chain running parallel
to the [101] direction (Fig. 7). Similarly, atom C24 in the molecule
at (x, y, z) acts as a hydrogen-bond donor, via H24, to atom O3 in
the molecule at (x ꢀ 1, y, z), so forming a C(7) chain running paral-
lel to the [100] direction (Fig. 8).
In the extended structure of 5b, shown in Fig. 10, an intermolec-
ular
rings of neighboring molecules. Details of
interactions are given in Table 4. The interactions produce
ꢃ ꢃ ꢃ
a chain running parallel to the [100] direction.
pꢃ ꢃ ꢃ
p
contact occurs between the three phenyl and pyrazole
p
ꢃ ꢃ ꢃ stacking
p
Compound 5b also contains three intermolecular CAHꢃ ꢃ ꢃ
p
p p
hydrogen bonds. The first is the C25 atom in the molecule at (x,

154
Z.S. Sßahin et al. / Journal of Molecular Structure 1006 (2011) 147–158
Fig. 8. Part of the crystal structure of 5b showing the formation of a chain along
[100] generated by the CAHꢃ ꢃ ꢃO hydrogen bonds. Hydrogen atoms have been
omitted for clarity.
Fig. 10. Part of the crystal structure of 5b showing the formation of a chain along
[100] generated by
for clarity.
pꢃ ꢃ ꢃp stacking interactions. Hydrogen atoms have been omitted
3.2. Optimized structures
The geometric parameters of 5a and 5b were calculated at the
B3LYP/6-31G(d,p) level by DFT method and listed in Table 2, to-
gether with corresponding experimental values. As can be seen
in Table 2, the bond lengths are extremely close to the experimen-
lated molecules in the gaseous phase whereas the experimental
values were based on molecules in the crystalline state.
The harmonic vibrational frequencies for 5a and 5b were calcu-
lated by using DFT method at 6-31G(d,p) level. In order to compare
the theoretical results with experimental values of those, all of the
calculated frequencies are scaled by 0.9627. Table 5 presents the
calculated vibrational frequencies and their experimentally mea-
sured values. The results obtained by the calculations have shown
a satisfactory consistency with the experimental data. The small
differences between experimental and calculated frequencies are
due to strong intermolecular interactions in solid phase.
tal values. The biggest deviations of the 0selected bond lengths are
0
0.036 ÅA (N(2)AC(12)) for 5a and 0.053 ÅA (N(1)AC(8)) for 5b. Fur-
thermore, superpositions of the molecular conformations of 5a
and 5b, as established by the DFT calculations and X-ray study,
show small conformational discrepancies between them (Fig. 11).
These discrepancies are originated from dihedral angles between
ring planes. The dihedral angles between the mean planes of pyr-
azole (A), methoxyphenyl (B) and benzoxazole (C) rings for 5a
and 5b are given Table 2. The small differences between the calcu-
lated and observed geometrical parameters can be attributed to
the fact that the theoretical calculations were carried out with iso-
GIAO 1H chemical shift values (with respect to TMS) have been
calculated using the B3LYP method with 6-31G(d,p) basis set and
generally compared to the experimental 1H chemical shift values.
The results of these calculations are tabulated in Table 6. We have
Fig. 9. Part of the crystal structure of 5b showing the formation of R22ð20Þ rings along [101]. Hydrogen atoms have been omitted for clarity.

Z.S. Sßahin et al. / Journal of Molecular Structure 1006 (2011) 147–158
155
Fig. 11. Atom-by-atom superimposition of the calculated structures (red) (B3LYP/6-31G(d,p)) over the X-ray structures (black) for the title compounds. Hydrogen atoms have
0
0
been omitted for clarity. The RMS overlay errors are 1.4597 ÅA for (5a) and 1.0615 ÅA for (5b). (For interpretation of the references to color in this figure legend, the reader is
referred to the web version of this article.)
Table 5
Characteristic IR absorption bands of the title molecules 5a and 5b.
Assignments
5a
5b
Experimental (cmꢀ1
)
Calculated (cmꢀ1
)
Experimental (cmꢀ1
)
Calculated (cmꢀ1
)
CAH str.
2942
1768
1673
1450–1650
2961
1813
1713
1588
3066
1789
1678
1450–1650
2976
1820
1713
1590
C@O str. (lactam)
C@O str. (hydrazide)
C@C str. + C@N str.
str.: Stretching.
calculated 1H chemical shift values (with respect to TMS) of
8.79–1.92 ppm (5a) and 8.75–3.12 ppm (5b) at B3LYP/6-31G(d,p)
level, whereas the experimental results are observed to be
7.87–2.29 ppm (5a) and 7.88–3.22 ppm (5b). To make a compari-
son with the experimental observation, we present correlation
graphics in Fig. 12 based on the calculations. As can be seen from
Fig. 12, experimental fundamentals are found to have a good corre-
lation with calculations.
The calculated results show that optimized geometries can well
reproduce the crystal structures and the theoretical vibrational fre-
quencies and chemical shift values show good agreement with
experimental ones.
Table 6
Theoretical and experimental 1H chemical shifts (with respect to TMS, all values in
ppm) for the title compounds.
Atom
5a
5b
The Mulliken charges of atoms and dipoles, and the molecular
orbital energies of the title compounds calculated at the B3LYP le-
vel are listed in Table 7. All oxygen and nitrogen atoms in both
molecules and chlorine atom in the 5b bear negative charges,
and the carbon atoms bonded to hydrogen atoms bear positive
charges and the remaining carbon atoms bear negative charges
in both molecules. Because of these charge distributions, the dipole
of molecules are 7.0077 for 5a and 5.9241 for 5b.
Molecular electrostatic potential (MEP) maps are often used for
the qualitative interpretation of electrophilic and nucleophilic
reactions [59], rationalize intermolecular interactions between po-
lar species, the calculation of atomic charges [60] and define re-
gions of local negative and positive potential in the molecule
[61]. This surface represents the distance from a molecule at which
a positive test charge experiences a certain amount of attraction or
repulsion. To investigate the reactive sites of 5a and 5b the molec-
ular electrostatic potentials were evaluated using the B3LYP/6-
31G(d,p) method. The negative (red) regions of MEP were related
to electrophilic reactivity and the positive (blue) regions to nucle-
ophilic reactivity. The electrostatic potential V(r) is also well suited
for analyzing processes based on the ‘‘recognition’’ of one molecule
by another, as in drug–receptor, and enzyme–substrate interac-
tions, because it is through their potentials that the two species
first ‘‘see’’ each other [62,63]. As it can be seen in Fig. 13, there
Experimental
Calculated
Experimental
Calculated
H1A
H1B
H1C
H3
H4
H7
2.29
2.29
2.29
6.73–6.93
7.21
7.07
5.04
5.21
3.23
1.92
2.56
2.49
7.02
7.15
7.66
4.51
5.47
3.8
3.21
6.4
7.54
7.69
7.71
7.8
8.79
7.14
6.76
–
7.77
3.67
4.24
3.77
3.84
4.27
3.8
–
–
–
6.88
6.88
7.39
5.08
5.22
–
–
–
7.16
7.21
6.84
4.5
5.34
3.12
3.79
5.31
7.51
7.71
7.72
7.81
8.75
7.49
7.09
7.93
7.47
3.79
4.16
3.82
–
H8A
H8B
H11A
H11B
H12
H14
H15
H16
H17
H18
H20
H21
H23
H24
H25A
H25B
H25C
H26A
H26B
H26C
3.22
3.90
5.54
3.90
5.54
7.85–7.87
7.49–7.52
7.49–7.52
7.49–7.52
7.85–7.87
6.73–6.93
6.73–6.93
–
6.73–6.93
3.71–3.72
3.71–3.72
3.71–3.72
3.71–3.72
3.71–3.72
3.71–3.72
7.85–7.88
7.16–7.19
7.16–7.19
7.16–7.19
7.85–7.88
7.48–7.52
7.48–7.52
7.48–7.52
7.48–7.52
3.72
3.72
3.72
–
–
–
–
–

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Z.S. Sßahin et al. / Journal of Molecular Structure 1006 (2011) 147–158
Fig. 12. Correlation graphics of calculated and experimental 1H chemical shifts of the title compounds.
Table 7
The charges of atoms and dipoles, and molecular orbital energies of the title compounds.
5a
5b
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
ꢀ0.3811
0.1039
ꢀ0.1372
ꢀ0.1260
0.2921
C(16)
C(17)
C(18)
C(19)
C(20)
C(21)
C(22)
C(23)
C(24)
C(25)
C(26)
C(27)
N(1)
ꢀ0.0790
ꢀ0.0902
ꢀ0.1049
0.1536
ꢀ0.1361
ꢀ0.1387
0.3253
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(14)
C(15)
C(16)
C(17)
C(18)
ꢀ0.1176
ꢀ0.0850
ꢀ0.1211
0.2990
C(19)
C(20)
C(21)
C(22)
C(23)
C(24)
C(25)
C(27)
N(1)
N(2)
N(3)
O(1)
O(2)
0.1587
ꢀ0.1212
ꢀ0.1153
0.3519
ꢀ0.1290
ꢀ0.1413
ꢀ0.0809
0.7809
ꢀ0.5875
ꢀ0.3161
ꢀ0.3405
ꢀ0.5203
ꢀ0.4929
ꢀ0.4864
ꢀ0.5164
ꢀ0.0254
0.3615
0.3618
ꢀ0.0711
ꢀ0.1424
0.5837
ꢀ0.1243
ꢀ0.1379
0.5826
0.3248
C(9)
ꢀ0.1891
ꢀ0.0773
ꢀ0.0798
0.7753
ꢀ0.5912
ꢀ0.3143
ꢀ0.3386
ꢀ0.4872
ꢀ0.5114
0.2719
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
O(1)
O(2)
O(5)
0.2692
ꢀ0.2838
ꢀ0.0008
ꢀ0.1044
ꢀ0.0901
ꢀ0.0785
ꢀ0.0921
ꢀ0.1336
ꢀ0.2842
ꢀ0.0057
0.1013
ꢀ0.1344
ꢀ0.0922
ꢀ0.5235
ꢀ0.5012
ꢀ0.5094
N(2)
N(3)
O(3)
O(4)
O(3)
O(4)
Cl(1)
Dipole (a.u.)
ETOTAL (eV)
EHOMO (eV)
ELUMO (eV)
7.0077
Dipole (a.u.)
ETOTAL (eV)
EHOMO (eV)
ELUMO (eV)
5.9241
ꢀ43112.3
ꢀ5.594
ꢀ1.592
–51432.3
ꢀ5.919
ꢀ1.654
Fig. 13. Molecular electrostatic potential maps of the title compounds (5a and 5b) calculated at B3LYP/6-31G(d,p) level.
are several possible sites of electrophilic attack in both molecules.
While the red regions are chiefly concentrated on the O atoms, po-
sitive potential sites are around the hydrogen atoms. The most
negative potential sites are on the O(2) atoms in the both mole-
cules and V(r) values are (expressed in a.u.) ꢀ0.0606 a.u. for 5a
and ꢀ0.0548 a.u for 5b. According to this results, the O atoms are
the most suitable regions for the electrophilic reaction and they
can easily react with atoms having high electrophilic attraction
such as metal atoms.
The frontier molecular orbitals play an important role in the
electric and optical properties, as well as in UV–vis spectra and
chemical reactions [64]. The HOMO and LUMO are also important

Z.S. Sßahin et al. / Journal of Molecular Structure 1006 (2011) 147–158
157
Fig. 14. Molecular orbital surfaces and energy levels given in parentheses for the HOMO and LUMO of the title compounds computed at B3LYP/6-31G(d,p) level.
in determining such properties as molecular reactivity and the
ability of a molecule to absorb light. Lowest unoccupied molecular
orbital (LUMO) is the molecular orbital of lowest energy that is not
occupied by electrons and represents the ability to obtain an elec-
tron, highest occupied molecular orbital (HOMO) is molecular orbi-
tal of highest energy that is occupied by electrons and represent
the ability to donate an electron [65]. Fig. 14 shows the distribu-
tions and energy levels of the HOMO ꢀ 1, HOMO, LUMO and
LUMO + 1 orbitals computed at the B3LYP/6-31G(d,p) level for 5a
and 5b. In 5a, the HOMOs are mainly localized on the around benz-
oxazole, methoxyphenyl and pyrazole rings where the LUMOs are
populated on the phenyl and pyrazole rings. Similarly, in 5b, the
HOMOs are mainly localized on the whole structure except hydro-
gen atoms and the LUMOs are populated on the phenyl and pyra-
zole rings. The HOMO–LUMO energy separation can be used as a
sign of kinetic stability [66]. A large HOMO–LUMO gap implies high
kinetic stability and low chemical reactivity, as it is energetically
unfavorable to add electron to a high-lying LUMO, to extract elec-
trons from low-lying HOMO [67].
elemental analyses, IR, 1H NMR, ESI-MS and single-crystal X-ray
diffraction. Each compounds, contain a phenyl ring (C13AC18)
and a methoxyphenyl group (C19AC24) attached to the central
pyrazole ring (N2/N3/C10AC12). In the both compounds, mole-
cules are linked into sheets by a combination of three CAHꢃ ꢃ ꢃO
hydrogen bonds and one CAHꢃ ꢃ ꢃ
p hydrogen bond, and these sheets
are linked into a two-dimensional framework structure by a com-
bination of two aromatic stacking interactions. Molecular
pꢃ ꢃ ꢃ
p
geometries from X-ray experiment of 5a and 5b in the ground state
have been compared using the Density Functional Theory (DFT)
with B3LYP/6-31G(d,p) basis set. DFT calculations and X-ray study
show small conformational discrepancies between them. The small
differences between the calculated and observed geometrical
parameters can be attributed to the fact that the theoretical calcu-
lations were carried out with isolated molecules in the gaseous
phase whereas the experimental values were based on molecules
in the crystalline state. A large HOMO–LUMO gap implies high ki-
netic stability and low chemical reactivity, as it is energetically
unfavorable to add electron to a high-lying LUMO, to extract elec-
trons from low-lying HOMO.
4. Conclusion
Supplementary data
1-[2-(5-Methyl-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3,
4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole (5a) and 1-[2-(5-
chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(4-methoxyph
enyl)-4,5-dihydro-1H-pyrazole (5b), were synthesized. The crystal
and molecular structures of 5a and 5b have been determined by
Crystallographic data for the structures reported in this article
have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication number 827823 (5a)–
827822 (5b). Copies of the data can be obtained free of charge on

158
Z.S. Sßahin et al. / Journal of Molecular Structure 1006 (2011) 147–158
[31] K.B. Lipkowitz, D. Boyd (Eds.), Reviews in Computational Chemistry, vols. 1–13,
VCH, New York, 1990–1999.
[32] W.J. Close, B.D. Tiffany, M.A. Spielman, J. Am. Chem. Soc. 71 (1949) 1265.
[33] R. Milcent, A. Akhnazarian, N. Lensen, J. Heterocycl. Chem. 33 (1996) 1829.
[34] U. Salgın-Gökßsen, N. Gökhan-Kelekçi, Ö. Göktasß, Y. Köysal, E. Kılıç, Sß. Ißsık, G.
Aktay, M. Özalp, Bioorg. Med. Chem. 15 (2007) 5738.
application to CCDC 12 Union Road, Cambridge CB21 EZ, UK. Fax:
+44 1223 336 033; e-mail: data_request@ccdc.cam.ac.uk.
Acknowledgements
[35] B. Çakır, Ö. Dag˘, E. Yıldırım, K. Erol, M.F. Sßahin, J. Fac. Pharm. Gazi 18 (2001) 99.
[36] W. Dawey, D.J. Tivey, J. Chem. Soc. (1958) 1230.
The authors wish to acknowledge the Faculty of Arts and Sci-
ences, Ondokuz Mayis University, Turkey, for the use of the Stoe
IPDS-II diffractometer (purchased from Grant No. F279 of the Uni-
versity Research Fund).
[37] F. Chimenti, E. Maccioni, D. Secci, A. Bolasco, P. Chimenti, A. Granese, O. Befani,
P. Turini, S. Alcaro, F. Ortuso, R. Cirilli, F. La Torre, M.C. Cardia, S. Distinto, J.
Med. Chem. 48 (2005) 7113.
[38] R. Cirilli, R. Ferretti, B. Gallinella, L. Turchetto, A. Bolasco, D. Secci, P. Chimenti,
M. Pierini, V. Fares, O. Befani, F. La Torre, Chirality 16 (2004) 625.
[39] J. Koo, J. Am. Chem. Soc. 75 (1953) 2000.
[40] Y. Ueno, L.D.S. Yadav, M. Okawara, Chem. Lett. 6 (1983) 831.
[41] N. Gökhan-Kelekçi, S. Koyunog˘lu, S. Yabanog˘lu, K. Yelekçi, Ö. Özgen, G. Uçar, E.
Erol, E. Kendi, A. Yesßilada, Bioorg. Med. Chem. 17 (2009) 675.
[42] G.M. Sheldrick, Acta Cryst. A 64 (2008) 112.
[43] L.J. Farrugia, WINGX—A Windows Program for Crystal Structure Analysis,
University of Glasgow, 1998.
References
[1] Y.F. Sun, Y.P. Cui, Dyes Pigm. 81 (2009) 27.
[2] A. Levai, Arkivoc ix (2005) 344.
[3] M. Shaharyar, A.A. Siddique, M.A. Ali, D. Sriram, P. Yogeeshwari, Bioorg. Med.
Chem. Lett. 16 (2006) 3947.
[4] I.G. Rathish, K. Javed, S. Ahmad, S. Bano, M.S. Alam, K.K. Pillai, S. Singh, V.
Bagchi, Bioorg. Med. Chem. Lett. 19 (2009) 255.
[5] B.S. Dawane, S.G. Konda, G.G. Mandwad, B.M. Shaikh, Eur. J. Med. Chem. 45
(2010) 387.
[6] G. Turan-Zitouni, P. Chevallet, F.S. Kılıç, K. Erol, Eur. J. Med. Chem. 35 (6) (2000)
635.
[7] R. Fioravanti, A. Bolasco, F. Manna, F. Rossi, F. Orallo, F. Ortuso, S. Alcaro, R.
Cirilli, Eur. J. Med. Chem. 45 (2010) 6135.
[8] F.F. Barsoum, H.M. Hosni, A.S. Girgis, Bioorg. Med. Chem. 14 (11) (2006) 3929.
[9] M. Amir, H. Kumar, S.A. Khan, Bioorg. Med. Chem. Lett. 18 (2008) 918.
[10] S. Khode, V. Maddi, P. Aragade, M. Palkar, P.K. Ronad, S. Mamledesai, A.H.M.
Thippeswamy, D. Satyanarayana, Eur. J. Med. Chem. 44 (2009) 1682.
[11] M.E. Shoman, M. Abdel-Aziz, O.M. Aly, H.H. Farag, M.A. Morsy, Eur. J. Med.
Chem. 44 (2009) 3068.
[12] K.S. Girisha, B. Kalluraya, V. Narayana, Padmashree, Eur. J. Med. Chem. 45
(2010) 4640.
[13] S. Kini, A.M. Gandhi, Indian J. Pharm. Sci. 70 (1) (2008) 102.
[14] V. Zsoldos-Mady, A. Csampai, R. Szabo, E. Meszaros-Alapi, J. Pasztor, F. Hudecz,
P. Sohar, Chem. Med. Chem. 1 (2006) 1119.
[15] D. Havrylyuk, B. Zimenkovsky, O. Vasylenko, L. Zaprutko, R. Lesyk, Eur. J. Med.
Chem. 44 (2009) 1396.
[16] B. Gowramma, S. Jubie, R. Kalirajan, S. Gomathy, K. Elango, Int. J. Pharm. Tech.
Res. 1 (2) (2009) 347.
[17] M. Shaharyar, M.M. Abdullah, M.A. Bakht, J. Majeed, Eur. J. Med. Chem. 45
(2010) 114.
[44] L.J. Farrugia, J. Appl. Crystallogr. 30 (1999) 837.
[45] L.J. Farrugia, J. Appl. Crystallogr. 30 (1997) 565.
[46] A.L. Spek, PLATON—A Multipurpose Crystallographic Tool, Utrecht, Utrecht
University, The Netherlands, 2005.
[47] C. Peng, P.Y. Ayala, H.B. Schlegel, M.J. Frisch, J. Comput. Chem. 17 (1996) 49.
[48] P.J. Stephens, F.J. Devlin, C.F. Chablowski, M.J. Frisch, J. Phys. Chem. 98 (1994)
11623.
[49] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
J.A. Montgomery Jr., J.T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S.
Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A.
Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa,
M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox,
H.P. Hratchian, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E.
Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y.
Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S.
Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K.
Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J.
Cioslowski, B.B. Stefanov, G. Lui, A. Liashenko, P. Piskorz, I. Komaromi, R.L.
Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M.
Challacombe, P.M.W.B. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez, J.A.
Pople, GAUSSIAN 03, Revision C.02, Gaussian Inc., Wallingford CT, 2004.
[50] A. Frisch, R.D. Dennington II, T.A. Keith, J. Milliam, A.B. Nielsen, A.J. Holder, J.
Hiscocks, GaussView Reference, Version 4.0, Gaussian Inc., Pittsburgh, 2007.
[51] J.P. Merrick, D. Moran, L. Radom, J. Phys. Chem. A 111 (2007) 11683.
[52] R. Ditchfield, J. Chem. Phys. 56 (1972) 5688.
[53] K. Wolinski, J.F. Hinton, P. Pulay, J. Am. Chem. Soc. 112 (1990) 8251.
[54] L. Infants, C.F. Foces, R.M. Claramunt, C. Lopez, J. Elguero, J. Mol. Struct. 447
(1998) 71.
[55] F.J. Cruz, S.H. Ortega, H.R. Olivares, J. Mol. Struct. 650 (2003) 223.
[56] J.Q. Puello, B.I. Obando, C.F. Foces, L. Infantes, R.M. Claramunt, P. Cabildo, J.A.
Jiminez, J. Elguero, Tetrahedron 53 (1997) 10783.
[57] F.H. Allen, O. Kennard, D.G. Watson, L. Brammer, A.G. Orpen, R. Taylor, J. Chem.
Soc., Perkin Trans. 2 (1987) S1.
[58] J. Bernstein, R.E. Davies, L. Shimoni, N.L. Chang, Angew. Chem. Int. Ed. Engl. 34
(1995) 1555.
[59] P. Politzer, K.C. Daiker, Models for Chemical Reactivity, The Force Concept in
Chemistry, Van Nostrand Reinhold, New York, 1981.
[60] S.R. Cox, D.E. Williams, J. Comput. Chem. 2 (1981) 304.
[61] R. Carbo, B. Calabuig, Comput. Phys. Commun. 55 (1989) 117.
[62] P. Politzer, D.G. Truhlar, Chemical Applications of Atomic and Molecular
Electrostatic Potentials, Plenum, New York, 1981.
[63] E. Scrocco, J. Tomasi, Top. Curr. Chem. 7 (1973) 95.
[64] I. Fleming, Frontier Orbitals and Organic Chemical Reactions, Wiley, London,
1976.
[65] E. Kavitha, N. Sundaraganesan, S. Sebastian, Indian J. Pure Appl. Phys. 48 (2010)
20.
[66] K.H. Kim, Y.K. Han, J. Jung, Theor. Chem. Acc. 113 (2005) 233.
[67] J. Aihara, J. Phys. Chem. A 103 (1999) 7487.
[18] O. Ruhoglu, Z. Özdemir, U. Çalißs, B. Gümüßsel, A.A. Bilgin, Arzneim. Forsch. 55
(8) (2005) 431.
[19] Z. Özdemir, B.H. Kandilci, B. Gümüßsel, Ü. Çalısß, A.A. Bilgin, Eur. J. Med. Chem. 42
(2007) 373.
[20] Ö.D. Can, Ü.D. Özkay, Z.A. Kaplancıklı, Y. Öztürk, Arch. Pharm. Res. 32 (2009)
1293.
[21] A. Shafiee, M. Bagheri, M. Shekarchi, M. Abdollahi, J. Pharm. Pharmaceut. Sci. 6
(3) (2003) 360.
[22] Z.A. Kaplancikli, G. Turan-Zitouni, A. Özdemir, Ö.D. Can, P. Pierre Chevallet, Eur.
J. Med. Chem. 44 (2009) 2606.
[23] H. Kawazura, Y. Takahashi, Y. Shiga, F. Shimad, N. Ohto, A. Tamura, Jpn. J.
Pharmacol. 73 (4) (1997) 317.
[24] G. Uçar, N. Gökhan, A. Yesßilada, A.A. Bilgin, Neurosci. Lett. 382 (2005) 327.
[25] K.M. Khan, U.R. Mughal, M.T.H. Khan, Z. Ullah, S. Perveen, M.I. Choudhary,
Bioorg. Med. Chem. 14 (2006) 6027.
[26] V. Tozzini, A.R. Bizzarri, V. Pellegrini, R. Nifosi, P. Giannozzi, A. Iuliano, S.
Cannistraro, F. Beltram, Chem. Phys. 287 (2003) 33.
[27] G. Ozturk, S. Alp, S. Timur, Dyes Pigm. 76 (2008) 792.
[28] J. Wouters, Curr. Med. Chem. 5 (1998) 137.
[29] A. Mai, M. Artico, M. Esposito, R. Ragno, G. Sbardella, S. Massa, Il Farmaco 58
(2003) 231.
[30] J. Wouters, F. Ooms, S. Jegham, J.J. Koenig, P. George, F. Durant, Eur. J. Med.
Chem. 32 (1997) 721.