Synthesis, crystal structures and theoretical calculations of new 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3,5-diphenyl-4,5-dihydro-(1H) -pyrazoles

Article abstract of DOI:10.1016/j.molstruc.2013.01.066

1-[2-(5-Chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3-methoxyphenyl) -4,5-dihydro-(1H)-pyrazole (5a), 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]- 3-phenyl-5-(3,4-dimethoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5b) and 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3-(4-methylphenyl)-5-(2, 3-dimethoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5c) were synthesized. The crystal and molecular structures of the compounds 5a, 5b and 5c were determined by elemental analyses, IR, ¹H NMR, ESI-MS and single-crystal X-ray diffraction. DFT method with 6-31G(d,p) basis set was used to calculate the optimized geometrical parameters, vibrational frequencies and chemical shift values. The calculated vibrational frequencies and chemical shift values were compared with experimental IR and ¹H NMR values. The results represented that there was a good agreement between experimental and calculated values of the compounds 5a-5c. In addition, DFT calculations of the compounds, molecular electrostatic potentials (MEPs) and frontier molecular orbitals were performed at B3LYP/6-31G(d,p) level of theory. Furthermore, compounds were tested against three Gram-positive bacteria: Staphylococcus aureus ATCC 29213 (American Type Culture Collection), methicillin resistant S. aureus (MRSA) ATCC 43300 and Enterococcus faecalis ATCC 29212; two Gram negative bacteria: Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853; and three fungi: Candida albicans ATCC 90028, Candida krusei ATCC 6258 and Candida parapsilosis ATCC 90018. In general, all of the compounds were found to be slightly active against tested microorganisms.

Full text of DOI:10.1016/j.molstruc.2013.01.066

Journal of Molecular Structure 1039 (2013) 71–83
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis, crystal structures and theoretical calculations of new
1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3,5-diphenyl-4,5-dihydro-(1H)-
pyrazoles
b
d
e
Umut Salgın Gökßsen a,b, Yelda Bingöl Alpaslan c, , Nesrin Gökhan Kelekçi , Sßamil Isßık , Melike Ekizog˘lu
⇑
a Turkish Medicines and Medical Devices Agency, Analyses and Control Laboratories, 06100 Ankara, Turkey
b Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 06100 Sıhhiye, Ankara, Turkey
c Giresun University, Faculty of Medicine, Department of Biophysics, 28100 Giresun, Turkey
d Ondokuz Mayıs University, Faculty of Arts and Sciences, Department of Physics, 55139 Kurupelit, Samsun, Turkey
e Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Microbiology, 06100 Sıhhiye, Ankara, Turkey
h i g h l i g h t s
"
"
"
"
We report the synthesis of three new 2-pyrazolines.
These compounds were characterized by 1H NMR, IR and X-ray crystallography.
The theoretical calculations were performed by DFT method.
The theoretical results were compared with experimental results.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 August 2012
Received in revised form 25 January 2013
Accepted 26 January 2013
Available online 1 February 2013
1-[2-(5-Chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3-methoxyphenyl)-4,5-dihydro-(1H)-pyrazole
(5a), 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3,4-dimethoxyphenyl)-4,5-dihydro-
(1H)-pyrazole (5b) and 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3-(4-methylphenyl)-5-(2,3-dime-
thoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5c) were synthesized. The crystal and molecular structures of
the compounds 5a, 5b and 5c were determined by elemental analyses, IR, 1H NMR, ESI-MS and single-
crystal X-ray diffraction. DFT method with 6-31G(d,p) basis set was used to calculate the optimized geo-
metrical parameters, vibrational frequencies and chemical shift values. The calculated vibrational fre-
quencies and chemical shift values were compared with experimental IR and 1H NMR values. The
results represented that there was a good agreement between experimental and calculated values of
the compounds 5a–5c. In addition, DFT calculations of the compounds, molecular electrostatic potentials
(MEPs) and frontier molecular orbitals were performed at B3LYP/6-31G(d,p) level of theory. Furthermore,
compounds were tested against three Gram-positive bacteria: Staphylococcus aureus ATCC 29213 (Amer-
ican Type Culture Collection), methicillin resistant S. aureus (MRSA) ATCC 43300 and Enterococcus faecalis
ATCC 29212; two Gram negative bacteria: Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC
27853; and three fungi: Candida albicans ATCC 90028, Candida krusei ATCC 6258 and Candida parapsilosis
ATCC 90018. In general, all of the compounds were found to be slightly active against tested
microorganisms.
Keywords:
5-Chloro-2-benzoxazolinone
4,5-Dihydro-(1H)-pyrazole
Crystal structure
DFT calculations
Antimicrobial activity
Ó 2013 Elsevier B.V. All rights reserved.
1. Introduction
useful intermediates in the production of pharmaceuticals, pesti-
cides and herbicides [2–4]. 2-Benzoxazolinone heterocycles are
Nitrogen and oxygen containing heterocyclic compounds have
received considerable attention due to their wide range of pharma-
cological activity [1]. 2-Benzoxazolinones and their derivatives are
considered ‘privileged scaffolds’ in the design of pharmacological
probes. These heterocycles have, in fact, high versatility in chemical
modifications, allowing changes to the characteristics of side-chains
on a rigid platform. Moreover, they have received considerable
attention from medicinal chemists, due to their capacity to mimic
a phenol or a catechol moiety in a metabolically stable template
⇑
Corresponding author. Tel.: +90 454 310 10 00.
E-mail address: yelda.alpaslan@giresun.edu.tr (Y.B. Alpaslan).
0022-2860/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2013.01.066

72
U.S. Gökßsen et al. / Journal of Molecular Structure 1039 (2013) 71–83
[5]. In the last 20 years, this class of compounds has led to the dis-
covery of a number of derivatives endowed with anti-inflammatory
and analgesic, antibacterial and antimicrobial activity [6–12].
acetate 2 [32]. The acid hydrazide 3 was prepared by the reaction
of ethyl 2-(5-chloro-2-benzoxazolinone-3-yl)acetate and hydra-
zine hydrate in ethanol [33]. On the other hand,
a,b-unsaturated
On the other hand,
a
,b-unsaturated ketones, especially 1,3-
carbonyl compounds (chalcones) 4a–4c were prepared by reacting
appropriate aldehydes and acetophenone derivatives under basic
condition according to the Claisen–Schmidt condensation [34–
37]. Compound 4c has been reported by Jaramillo and coworkers
[37]. Since there is no information available for the preparation
and spectral characteristics, this compound was included in our re-
search program and characterized by spectral data. These data are
given in Supplementary data. The reaction of hydrazide 3 with
chalcones 4a–4c in n-propanol under acidic condition gave 1-[2-
(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3,5-diphenyl-4,5-dihy-
dro-(1H)-pyrazoles 5a–5c.
diarylprop-2-en-1-ones, commonly known as chalcones, have re-
ceived much attention in medicinal chemistry. Chalcones are such
small molecules that have been known to exhibit a wide range of
activities including antibacterial, antifungal, antitubercular and
antioxidant [13–17]. They are important due to their biological
properties, besides serving as important intermediates for the syn-
thesis of a large number of heterocyclic systems. Some heterocyclic
systems based on chalcone precursors are benzothiazepines, ben-
zodiazepines, benzoxazepines, pyrimidines, pyrazoles, and oxaz-
oles [18,19].
4,5-Dihydro-(1H)-pyrazoles are another class of small molecules
that can be prepared using chalcones as the starting material [17].
4,5-Dihydro-(1H)-pyrazoles can be conveniently synthesized by
the treatment of chalcones with hydrazine derivatives in basic and
acidic media [20–22]. In this method, hydrazones are formed as
intermediates, which can be subsequently cyclized to 4,5-dihydro-
(1H)-pyrazoles in the presence of a suitable cyclizing reagent like
acetic acid [23,24]. 4,5-Dihydro-(1H)-pyrazoles are also useful lead
molecules that are found to act as antibacterial, antifungal, antitu-
bercular, analgesic, anti-inflammatory and antidepressant agents
[24–29]. 4,5-Dihydro-(1H)-pyrazoles are also used in the treatment
of Parkinson’s, Alzehimer’s disease and Cerebral edema [30,31].
In the current study, we aimed to obtain new compounds con-
taining both 4,5-dihydro-(1H)-pyrazole and benzoxazolinone rings
in the same structure. Chemical structures of compounds were
confirmed by IR, 1H NMR, ESI-MS, single-crystal X-ray diffraction
and quantum chemical methods. The geometrical parameters,
vibrational frequencies and 1H chemical shift values of the synthe-
sized compounds in the ground state were calculated using the
DFT method (B3LYP) with 6-31G(d,p) basis set. Additionally,
molecular electrostatic potentials (MEPs) and frontier molecular
orbitals (FMOs) were calculated. Finally, the synthesized com-
pounds were tested for their antibacterial and antifungal activities
against five bacteria and three fungi.
2.2.1. General procedure for the preparation of 4,5-dihydro-(1H)-
pyrazoles (5)
Chalcone (1 mmol) and hydrochloric acid (8 drops) were added
to a solution of acetohydrazide (1 mmol) in DMF and n-propanol
(2–20 mL). The solution was refluxed for approximately 120 h
[38] and then cooled. The precipitated solid was recrystallized or
the crude material was purified by silica gel flash chromatography.
2.2.1.1. 1-[2-(5-Chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-
(3-methoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5a).
Compound 5a was obtained by the reaction of compound 3 with
compound 4a. The precipitated solid was recrystallized from ace-
tone–water (3:1) to give 4.2% of 5a as a white-off crystal. M.p.:
212–214 °C. IR (KBr) cmꢀ1: 3027 (CAH), 1763, 1669 (C@O), 1609,
1574 (C@C, C@N); 1H NMR (400 mHz, DMSO-d6) d (ppm): 3.22
(dd, 1H, HA, JAB:18.4 Hz, JAX:5.2 Hz), 3.73 (s, 3H, AOCH3), 3.92 (dd,
1H, HB, JAB:18.2 Hz, JBX:11.6 Hz), 5.10 (d, 1H, NACH1H2ACO,
J:18.0 Hz), 5.29 (d, 1H, NACH1H2ACO, J:17.6 Hz), 5.57 (dd, 1H,
HX, JBX:11.6 Hz, JAX:5.2 Hz), 6.79–6.84 (m, 3H, phenyl-3H), 7.18
(dd, 1H, 5-chloro-2-benzox.-H6, J67:8.8 Hz, J46:2.4 Hz), 7.25 (t, 1H,
phenyl-H), 7.39 (d, 1H, 5-chloro-2-benzox.-H7, J67:8.4 Hz), 7.50–
7.52 (m, 4H, 5-chloro-2-benzox.-H4 and phenyl-3H), 7.85–7.87
(m, 2H, phenyl-2H); ESI-MS: m/z(%): 502 ([M + K + 2]+, 3%), 500
([M + K]+, 7%), 487 ([M + H + Na + 2]+ 10%), 486 ([M + Na + 2]+,
39%), 485 ([M + H + Na]+, 30%), 484 ([M + Na]+, 100%), 462
([M + H]+, 4%). Calculated for C25H20ClN3O4: C, 65.01; H, 4.36; N,
9.10. Found C, 65.25; H, 4.695; N, 9.118. IR, 1H NMR and Mass spec-
trums of the compound 5a were shown in Supplementary data.
2. Experimental and calculations
2.1. Chemistry
All chemicals and solvents used in the present study were pur-
chased from Merck A.G., Aldrich Chemical. Melting points 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
Software Version 2.0) spectrometer using potassium bromide
plates and the results were expressed in wave number (cmꢀ1).
1H NMR spectra were recorded on a Bruker AC 400 MHz spectrom-
eter using dimethylsulphoxide (DMSO-d6) with chemical shifts
being reported as d (ppm) from TMS. Mass spectra were obtained
via an electron impact technique using Waters 2695 Alliance
Micromass ZQ LC/MS in methanol. Elemental analyses (C, H, N)
were performed on Leco CHNS 932 analyzer in the laboratory of
Ankara University. The purity of the compounds were assessed
by TLC on silicagel HF254+366 (E. Merck, Darmstadt, Germany).
2.2.1.2. 1-[2-(5-Chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-
(3,4-dimethoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5b).
Compound 5b was obtained by the reaction of compound 3 with
compound 4b. The precipitated solid was recrystallized from ace-
tone–water (3:1) to give 13.6% of 5b as a white crystal. M.p.:
197–199 °C. IR (KBr) cmꢀ1: 3000 (CAH), 1765, 1672 (C@O), 1617,
1592 (C@C, C@N); 1H NMR (400 mHz, DMSO-d6) d (ppm): 3.23
(dd, 1H, HA, JAB:18.4 Hz, JAX:4.8 Hz), 3.71 (s, 3H, AOCH3), 3.73 (s,
3H, AOCH3), 3.90 (dd, 1H, HB, JAB:18.0 Hz, JBX:11.2 Hz), 5.09 (d,
1H, NACH1H2ACO, J:18.0 Hz), 5.28 (d, 1H, NACH1H2ACO,
J:17.6 Hz), 5.54 (dd, 1H, HX, JBX:11.6 Hz, JAX:5.2 Hz), 6.75 (dd, 1H,
phenyl-H, J1:8.4 Hz, J2:2.0 Hz), 6.82 (d, 1H, phenyl-H, J:2.0 Hz),
6.88 (d, 1H, phenyl-H, J:8.8 Hz), 7.18 (dd, 1H, 5-chloro-2-benzox.-
H6, J67:8.8 Hz, J47:2.4 Hz), 7.39 (d, 1H, 5-chloro-2-benzox.-H7,
J67:8.4 Hz), 7.49–7.52 (m, 4H, 5-chloro-2-benzox.-H4 and phenyl-
3H), 7.85–7.87 (m, 2H, phenyl-2H); ESI-MS: m/z (%): 532
([M + K + 2]+, 3%), 530 ([M + K]+, 7%), 517 ([M + H + Na + 2]+, 11%),
516 ([M + Na + 2]+, 43%), 515 ([M + H + Na]+, 34%), 514 ([M + Na]+,
100%), 492 ([M + H]+, 2%). Calculated for C26H22ClN3O5: C, 63.48;
H, 4.51; N, 8.54. Found C, 63.10; H, 4.441; N, 8.700. IR, 1H NMR
and Mass spectrums of the compound 5b were shown in Supple-
mentary data.
2.2. Synthesis
The synthesis pathway of novel 4,5-dihydro-(1H)-pyrazole
compounds is given in Scheme 1. Treatment of 5-chloro-2-benzox-
azolinone 1 with ethyl chloroacetate in K2CO3/acetone gave the
N-alkylated product ethyl 2-(5-chloro-2-benzoxazolinone-3-yl)

U.S. Gökßsen et al. / Journal of Molecular Structure 1039 (2013) 71–83
73
Scheme 1. Synthesis of novel 4,5-dihydro-(1H)-pyrazole compounds.
2.2.1.3. 1-[2-(5-Chloro-2-benzoxazolinone-3-yl)acetyl]-3-(4-methyl-
phenyl)-5-(2,3-dimethoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5c).
Compound 5c was obtained by the reaction of compound 3 with
compound 4c. The solution was purified by chromatography and
the precipitated solid was recrystallized from acetone–water
(3:1) to give 1.8% of 5c as a white crystal. M.p.: 183–184 °C. IR
(KBr) cmꢀ1: 2960 (CAH), 1771, 1681 (C@O), 1613, 1589 (C@C,
C@N); 1H NMR (400 mHz, DMSO-d6) d (ppm): 2.38 (s, 3H, ACH3),
3.11 (dd, 1H, HA, JAB:18.0 Hz, JAX:5.2 Hz), 3.74 (s, 3H, AOCH3),
3.79 (s, 3H, AOCH3), 3.88 (dd, 1H, HB, JAB:18.0 Hz, JBX:12.0 Hz),
5.10 (d, 1H, NACH1H2ACO, J:18.0 Hz), 5.22 (d, 1H, NACH1H2ACO,
J:18.0 Hz), 5.67 (dd, 1H, HX, JBX:11.8 Hz, JAX:5.2 Hz), 6.70 (dd, 1H,
phenyl-H, J1:7.2 Hz, J2:1.6 Hz), 6.96–7.02 (m, 2H, phenyl-2H),
7.18 (dd, 1H, 5-chloro-2-benzox.-H6, J67:8.6 Hz, J46:2.0 Hz), 7.32
(d, 2H, 4-methylphenyl-2H, J:8.0 Hz), 7.39 (d, 1H, 5-chloro-2-ben-
zox.-H7, J67:8.4 Hz), 7.48 (d, 1H, 5-chloro-2-benzox.-H4, J46:2.0 Hz),
7.75 (d, 2H, 4-methylphenyl-2H, J:8.0 Hz); ESI-MS: m/z (%): 544
([M + K]+, 3%), 531 ([M + H + Na + 2]+, 7%), 530 ([M + Na + 2]+,
19%), 529 ([M + H + Na]+, 16%), 528 ([M + Na]+, 51%), 508
([M + H + 2]+, 35%), 507 ([M + 2]+, 29%), 506 ([M + H]+, 100%), 368
([M+ ꢀ [C6H3A(OCH3)2]], 7%). Calculated for C27H24ClN3O5: C,
64.10; H, 4.78; N, 8.31. Found: C, 64.00; H, 4.740; N, 8.538. IR, 1H
NMR and Mass spectrums of the compound 5c were shown in Sup-
plementary data.
value of the parent atom for CH, CH2 and CH3. Molecular diagrams
were created using ORTEP-III [41]. Geometric calculations were
performed with PLATON [42].
2.4. Theoretical methods
The geometries of compounds 5a–5c were optimized by using
DFT method, starting from the experimental structures. DFT calcu-
lations with the 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 [43,44] were performed
with the Gaussian 03 software package [45], and GaussView visu-
alization program [46]. The harmonic vibrational frequencies were
calculated at the same level of theory for the optimized structure
and the obtained frequencies were scaled by 0.9627 [47]. To inves-
tigate the reactive regions of the compounds 5a–5c, the molecular
electrostatic potentials were calculated using the same method.
The optimized geometries of compounds 5a–5c and the reference
compound tetramethylsilane (TMS) optimized at B3LYP/6-
31G(d,p) level were considered for 1H NMR chemical shifts using
the Gauge-Independent Atomic Orbital (GIAO) methodology
[48,49]. The 1H chemical shifts were converted to the TMS scale
by subtracting the calculated absolute chemical shielding of TMS
(d = R0
ꢀ
R, where d is the chemical shift, R is the absolute shield-
ing and R0 is the absolute shielding of TMS), whose value is 31.76
for B3LYP/6-31G(d,p). Additionally, the frontier molecular orbitals
were evaluated using the same method.
2.3. Crystallography
Single-crystals of compounds 5a, 5b and 5c suitable for data
collection were selected and performed on a STOE IPDS II diffrac-
2.5. Biological activity
tometer with graphite monochromated MoK
a
radiation
k = 0.71073 Å. The structures were solved by direct-methods using
SHELXS-97 [39] and refined by full-matrix least-squares methods
on F2 using SHELXL-97 [39] from within the WINGX [40] suite of
software. The parameters for data collection and structure refine-
ment of compounds 5a–5c are listed in Table 1. All non-hydrogen
atoms were refined with anisotropic parameters. Hydrogen atoms
bonded to carbon were placed in calculated positions (CAH@0.93–
0.97 Å) and treated using a riding model with U = 1.2 times the U
The newly synthesized compounds were screened for their anti-
bacterial activity against Staphylococcus aureus ATCC 29213, meth-
icillin resistant S. aureus ATCC 43300, Enterococcus faecalis ATCC
29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa
ATCC 27853 bacterial strains and for their antifungal activity
against three Candida species: Candida albicans ATCC 90028, C. kru-
sei ATCC 6258 and C. parapsilosis ATCC 90018. Broth microdilution
method recommended by the Clinical and Laboratory Standards

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U.S. Gökßsen et al. / Journal of Molecular Structure 1039 (2013) 71–83
Table 1
Parameters for data collection and structure refinement of compounds 5a–5c.
5a
5b
5c
Crystal data
Chemical formula
Crystal shape/color
Formula weight
Crystal system
C
25H20ClN3O4
C26H22ClN3O5
Prism./white
491.92
Orthorhombic
P212121
C27H24ClN3O5
Prism./white
505.94
Monoclinic
P21/c
Prism./white-off
461.89
Monoclinic
Cc
Space group
Unit cell parameters
a = 4.5981(3) Å
b = 26.6677(15) Å
c = 17.6682(13) Å
b = 93.144(5)°
2163.2(2) Å3
4
a = 8.2442(4) Å
b = 13.6723(7) Å
c = 20.9866(10) Å
a = 11.194(5) Å
b = 18.467(5) Å
c = 13.981(5) Å
b = 121.196(5)°
2472.2(16) Å3
4
Volume
2365.6(2) Å3
4
1.381
0.21
Z
Dx (Mg cmꢀ3
)
1.418
0.22
1.359
0.20
l
(mmꢀ1
)
F000
960
1024
0.50 ꢁ 0.43 ꢁ 0.30
1056
0.69 ꢁ 0.40 ꢁ 0.20
Crystal size (mm3)
0.44 ꢁ 0.21 ꢁ 0.07
Data collection
Diffractometer/meas. meth
Absorption correction
Tmin
STOE IPDS II/w-scan
Integration
0.942
STOE IPDS II/w-scan
Integration
0.979
STOE IPDS II/w-scan
Integration
0.904
Tmax
0.983
0.988
0.964
No. of measured, indep. and obsv. reflections
9746, 3965, 2460
11226, 4624, 3598
22989, 4871, 2921
Criterion for observed reflections
I > 2r
(I)
I > 2
r(I)
I > 2r(I)
Rint
hmax
0.053
26.0
0.050
26.0
0.074
26.0
Refinement
Refinement on
F2
F2
F2
R[F2 > 2
r
(F2)], wR, S
0.038, 0.081, 0.87
0.037, 0.087, 0.94
0.059, 0.129, 1.04
No. of reflection
No. of parameters
Weighting scheme
3965
298
4624
317
4871
326
w = 1/[
r
2(F20)+(0.0364P)2]
w = 1/[
r
2(F20)+(0.0506P)2]
w = 1/[r
2(F20)+(0.0539P)2]
P=(F20 + 2F2c )/3
0.10, ꢀ0.18
P=(F20 + 2F2c )/3
0.11, ꢀ0.11
P=(F20 + 2F2c )/3
0.17, ꢀ0.30
D
qmax, D )
qmin (e Åꢀ3
Institute (CLSI, formerly NCCLS) was used to determine the antimi-
crobial activity [50,51]. Antibacterial activity test was performed in
Mueller–Hinton broth (MHB, Difco Laboratories, Detroit, MI, USA);
N3AC10 bond lengths of 1.288(3) Å for compound 5a, 1.283(2) Å
for compound 5b and 1.289(3) Å for compound 5c are indicative
of significant double-bond character. The N2AC12 and N2AC9
bond distances deviate significantly from the mean value of NAC
distances in pyrazole rings [52–55]. The pyrazole rings are planar,
the maximum deviations from the least-squares planes being
0.0202(17) Å for atom C12 in compound 5a, 0.0379(14) Å for atom
C12 in compound 5b and 0.0041(11) Å for atom N2 in compound
5c. The bond lengths and the bond angles in all molecules are in
good agreement with our previous work [55].
for antifungal test, RPMI-1640 medium with
L-glutamine
(ICN-Flow, Aurora, OH, USA), buffered with MOPS buffer (ICN-Flow,
Aurora, OH, USA) was used. The inoculum densities were approxi-
mately 5 ꢁ 105 cfu/mL and 0.5–2.5 ꢁ 103 cfu/mL for bacteria and
fungi, respectively. Each compound was dissolved in DMSO. Final
twofold concentrations were prepared in the wells of the microti-
ter plates, between 2048 and 2 lg/mL. Microtiter plates were incu-
bated at 35 °C for 18–24 h for bacteria and 48 h for fungi. After the
incubation period, minimum inhibitory concentration (MIC) values
were defined as the lowest concentration of the compounds that
inhibits the visible growth of the microorganisms. Ciprofloxacin
and fluconazole were used as reference antibiotics for bacteria
Compound 5a crystallizes in the monoclinic space group Cc
with Z = 4 in the unit cell. The asymmetric unit in the crystal struc-
ture contains only one molecule. The molecular structure of com-
pound 5a is not planar but the ring systems are almost planar.
The maximum deviations are 0.0146(23) Å for atom C7 in the 5-
chloro-2-benzoxazolinone ring A(N1/O1/C1AC7), 0.0043(25) Å for
atom C17 in the phenyl ring B(C13AC18) and ꢀ0.0107(26) Å for
atom C23 in the methoxyphenyl ring C(C19AC24). The dihedral an-
gles between the 5-chloro-2-benzoxazolinone plane A, the phenyl
plane B and the methoxyphenyl plane C are 81.82(7)° (A/B),
52.65(9)° (A/C) and 56.08(11)° (B/C) for compound 5a. The crystal
structure is stabilized by intermolecular CAHꢂ ꢂ ꢂO hydrogen bonds
(Table 2). Atom C2 in the molecule at (x, y, z) acts as a hydrogen-
bond donor, via H2, to atom O3 in the molecule at (1 + x, y, z), so
forming a C(7) chain running parallel to the [100] direction [56].
Similarly, atom C25 in the molecule at (x, y, z) acts as a hydro-
gen-bond donor, via H25B, to atom O3 in the molecule at (1 + x,
y, z), so forming a C(10) chain running parallel to the [100] direc-
tion. The combination of the C(7) and C(10) chains generates a
chain of edge-fused R12(15), rings running parallel to the [100]
direction (Fig. 2).
and fungi, respectively (64–0.0625 lg/mL).
3. Results and discussion
3.1. Supramolecular structures
The molecular structures of the compounds 5a–5c determined
by X-ray crystallography have been depicted in Figs. 1, 3 and 6
respectively. Each compound contains the central pyrazole ring
(N2/N3/C10AC12). The bond lengths in the pyrazole ring show
partial aromatic character, which suggests a delocalized p-electron
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

U.S. Gökßsen et al. / Journal of Molecular Structure 1039 (2013) 71–83
75
Fig. 1. The molecular structure of compound 5a, shown with 30% probability displacement ellipsoids and illustrating the atom-numbering scheme.
Table 2
Hydrogen-bond geometry of compounds 5a–5c (Å, °).
The compound 5b (Fig. 3) is not planar like compound 5a. The
dihedral angles between the 5-chloro-2-benzoxazolinone plane
A(N1/O1/C1AC7), the phenyl plane B(C13AC18) and the dime-
thoxyphenyl plane C(C19AC24) are 78.51(5)° (A/B), 79.54(5)°
(A/C) and 74.47(7)° (B/C). The crystal packing of the compound
5b is stabilized by two intermolecular CAHꢂ ꢂ ꢂO hydrogen bonds,
details of which are given in Table 2 (Figs. 4 and 5).
The molecular structure of compound 5c is not planar. The
dihedral angles between the 5-chloro-2-benzoxazolinone plane
A(N1/O1/C1AC7), the methylphenyl plane B(C13AC18), and the
dimethoxyphenyl plane C(C19AC24) are 83.46(9)° (A/B),
71.58(6)° (A/C) and 83.86(10)° (B/C). The crystal structure does
not exhibit classical hydrogen bond. However, there are three
5a
5b
5c
DAHꢂ ꢂ ꢂA
DAH
0.93
0.96
Hꢂ ꢂ ꢂA
2.41
2.52
Dꢂ ꢂ ꢂA
DAHꢂ ꢂ ꢂA
154
148
C2AH2ꢂ ꢂ ꢂO3i
C25AH25Bꢂ ꢂ ꢂO3i
3.270 (4)
3.368 (5)
DAHꢂ ꢂ ꢂA
DAH
0.97
0.93
Hꢂ ꢂ ꢂA
2.49
2.59
Dꢂ ꢂ ꢂA
DAHꢂ ꢂ ꢂA
154
135
C8AH8Bꢂ ꢂ ꢂO2i
C25AH25Bꢂ ꢂ ꢂO3ii
3.395 (3)
3.313 (3)
DAHꢂ ꢂ ꢂA
DAH
0.98
0.93
0.96
Hꢂ ꢂ ꢂA
2.98
2.79
2.91
Dꢂ ꢂ ꢂA
DAHꢂ ꢂ ꢂA
142
155
C12AH12ꢂ ꢂ ꢂCg4i
C22AH22ꢂ ꢂ ꢂCg4ii
C26AH26Aꢂ ꢂ ꢂCg3iii
3.794 (3)
3.659 (4)
3.758 (4)
148
Compound 5a for symmetry codes: (i) x + 1, y, z.
Compound 5b for symmetry codes: (i) x ꢀ 1/2, ꢀy + 3/2, ꢀz + 1; (ii) ꢀx + 1/2, ꢀy + 1,
z ꢀ 1/2.
Compound 5c for symmetry codes: (i) ꢀx + 1, ꢀy + 1, ꢀz + 1; (ii) ꢀx, ꢀy + 1, ꢀz + 1;
(iii) ꢀx, ꢀy + 1, ꢀz.
CAHꢂ ꢂ ꢂ
p interactions, details of which are given in Table 2
(Fig. 7).
Cg3 and Cg4 are the centroids of the C1AC6, C13AC18 rings, respectively.
Fig. 2. The packing of compound 5a, showing the formation of a chain edge-fused R12(15) rings along [100]. Hydrogen atoms have been omitted for clarity.

76
U.S. Gökßsen et al. / Journal of Molecular Structure 1039 (2013) 71–83
Fig. 3. The molecular structure of compound 5b, shown with 30% probability displacement ellipsoids and illustrating the atom-numbering scheme.
Fig. 4. Part of the crystal structure of compound 5b, showing the formation of a chain along [100] generated by CAHꢂ ꢂ ꢂO hydrogen bonds. Hydrogen atoms have been
omitted for clarity.

U.S. Gökßsen et al. / Journal of Molecular Structure 1039 (2013) 71–83
77
Fig. 5. Part of the crystal structure of compound 5b, showing the formation of a chain along [001] generated by CAHꢂ ꢂ ꢂO hydrogen bonds. Hydrogen atoms have been
omitted for clarity.
Fig. 6. The molecular structure of compound 5c, shown with 30% probability displacement ellipsoids and illustrating the atom-numbering scheme.
3.2. Optimized geometry and electronic structure
molecular skeleton with that obtained from X-ray diffraction, giv-
ing a RMSE of 0.750 Å for compound 5a, 0.664 Å for compound 5b
and 0.024 Å for compound 5c (see Fig. 8). These differences are due
to intermolecular interactions. They have been much more ob-
served especially for compounds 5a and 5b. These studies indicate
that the B3LYP calculation reproduce the geometry of the com-
pounds well.
The nuclei and electrons of a molecule produce an electrostatic
potantial V(r) at any r in the space of a molecule. Its value is given
by
The geometric parameters of compounds 5a–5c were calculated
at the B3LYP/6-31G(d,p) level by DFT method and listed together
with corresponding experimental values in Table 3. As it can be
seen in Table 3, most of the calculated bond lengths and the bond
angles are slightly different from the experimental ones. 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. Acccording to X-ray and DFT studies, the
dihedral angles between the mean planes of A (N1/O1/C1AC7), B
(C13AC18) and C (C19AC24) rings for compounds 5a–5c are given
Table 3. A logical method for globally comparing the structures ob-
tained with the theoretical calculations is by superimposing the
Z
ðr0Þ
X
ZA
jRA ꢀ rj
q
VðrÞ ¼
ꢀ
dr0
ð1Þ
jr0 ꢀ rj
A
where ZA is the charge of nucleus A, located at RA,
q
(r0) is the mol-
ecule’s electronic density and r0 is the dummy integration variable

78
U.S. Gökßsen et al. / Journal of Molecular Structure 1039 (2013) 71–83
Fig. 7. The packing of compound 5c, showing the R22(12), R22(20) and R22(12) ring patterns. Hydrogen atoms have been omitted for clarity.
Table 3
Selected bond lengths, angles and dihedral angles for compounds 5a–5c.
5a
5b
5c
X-ray
B3LYP/6-31G(d,p)
X-ray
B3LYP/6-31G(d,p)
X-ray
B3LYP/6-31G(d,p)
Bond lengths (Å)
N2AN3
1.399(3)
1.288(3)
1.499(4)
1.539(4)
1.465(4)
1.216(4)
1.196(4)
1.478(3)
1.343(4)
1.450(3)
1.363(4)
1.394(3)
1.737(3)
1.379
1.293
1.519
1.554
1.466
1.221
1.204
1.485
1.370
1.442
1.389
1.390
1.761
1.397(2)
1.283(2)
1.500(3)
1.542(3)
1.474(3)
1.225(2)
1.200(3)
1.474(3)
1.347(2)
1.451(3)
1.354(3)
1.387(3)
1.729(3)
1.378
1.293
1.519
1.553
1.466
1.221
1.205
1.489
1.369
1.442
1.388
1.391
1.761
1.390(3)
1.289(3)
1.502(3)
1.532(4)
1.461(3)
1.216(3)
1.207(4)
1.481(3)
1.348(3)
1.436(4)
1.365(4)
1.394(4)
1.731(4)
1.380
1.293
1.519
1.552
1.464
1.224
1.204
1.488
1.365
1.442
1.388
1.390
1.761
N3AC10
C10AC11
C11AC12
C10AC13
C9AO3
C7AO2
N2AC12
N2AC9
N1AC8
N1AC7
N1AC1
C3ACl1
Bond angles (°)
N2AC9AC8
N3AC10AC13
N1AC8AC9
114.6(3)
121.1(3)
111.9(2)
115.07
122.04
111.14
115.31(17)
121.16(18)
110.68(16)
115.01
122.00
111.30
115.1(2)
121.5(2)
111.1(2)
115.05
121.99
111.24
Dihedral angles (°)
A/B
A/C
B/C
81.82(7)
52.65(9)
56.08(11)
78.95
75.13
85.33
78.51(5)
79.54(5)
74.47(7)
75.84
66.78
89.14
83.46(9)
71.58(6)
83.86(10)
76.87
70.71
86.05
(A: N1/O1/C1AC7, B: C13AC18 and C: C19AC24).
[57]. The MEP, V(r), is well suited for analyzing processes based on
the molecular recognition, as in drug-receptor, and enzyme–sub-
strate interactions [58–60]. MEP maps of the compounds 5a–5c
(Fig. 9) were calculated by using the geometry obtained from DFT
method at the B3LYP/6-31G(d,p). The negative (red1 and yellow)
and the positive (blue) regions in the MEP were related to electro-
philic reactivity and nucleophilic reactivity, respectively. Negative
electrostatic potential regions are mainly localized over the O atoms.
The most negative regions are on the O2 atoms in compounds 5a–5c
and V(r) values are ꢀ0.059 a.u. for compound 5a, ꢀ0.057 a.u. for
compounds 5b and 5c. The most positive regions in MEP maps are
on the H atoms bonded to phenyl ring and their V(r) values are
0.049 a.u., 0.045 a.u. and 0.047 a.u. for compounds 5a, 5b and 5c,
respectively. These simulated MEP maps appear that the negative
potential regions are localized on oxygen atoms, while the positive
ones are around the hydrogen atoms. These regions give information
about metallic bondings, non-colavent and intermolecular
interactions.
1
For interpretation of color in Fig. 9, the reader is referred to the web version of
this article.

U.S. Gökßsen et al. / Journal of Molecular Structure 1039 (2013) 71–83
79
Fig. 8. Atom-by-atom superimposition of the calculated structures (red) over the X-ray structures (blue) for the synthesized compounds. Hydrogen atoms have been omitted
for clarity. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 9. Molecular electrostatic potential maps of the synthesized compounds calculated at B3LYP/6-31G(d,p) level.
The distributions and energy levels of the frontier molecular
orbitals (FMOs) were computed at B3LYP/6-31G(d,p) level for the
compounds and are shown in Fig. 10. In compound 5a, the highest
occupied molecular orbitals (HOMOs) are mainly localized on the
5-chloro-2-benzoxazolinone, methoxyphenyl and pyrazole rings
while the lowest-lying unoccupied molecular orbitals (LUMOs)
are populated on the phenyl and pyrazole rings. In compound 5b,
while the HOMO are mainly localized on the dimethoxyphenyl
and pyrazole rings, the LUMO are localized on the phenyl and pyr-
azole rings. Similarly, in compound 5c, the LUMO are populated
like compounds 5a–5b and the HOMO are localized on almost
the whole structure. Additionaly HOMO and LUMO energies and
chemical hardness were also calculated with the same level of the-
ory and the results were given in Table 4. The chemical hardness is

80
U.S. Gökßsen et al. / Journal of Molecular Structure 1039 (2013) 71–83
Fig. 10. Molecular orbital surfaces and energy levels given in parantheses for the HOMO and LUMO of the synthesized compounds computed at B3LYP/6-31G(d,p) level.
Table 4
3.3. Spectroscopic characterization
Frontier orbital energies and hardnesses.
5a
5b
5c
The IR spectra of the compounds 5a, 5b and 5c showed two
stretching bands at 1771–1763 cmꢀ1 and 1681–1669 cmꢀ1 due to
carbonyl function of lactam and acetyl group, respectively. All
compounds showed absorption bands in the regions 1617–
1609 cmꢀ1 and 1592–1574 cmꢀ1 corresponding to C@C and C@N
stretching bands. Existence of C@N stretching bands and disap-
pearance of NAH stretching bands proved the closure of 4,5-dihy-
dro-(1H)-pyrazole ring. Also aromatic and aliphatic CAH stretching
EHOMO (eV)
ELUMO (eV)
ꢀ5.984
ꢀ1.713
4.271
ꢀ5.607
ꢀ1.656
3.951
ꢀ5.873
ꢀ1.548
4.325
D
E (eV)
g
(eV)
2.136
1.976
2.162
quite useful to rationalize the relative stability and reactivity of
chemical species. Hard species having large HOMO–LUMO gap will
be more stable and less reactive than soft species having small
HOMO–LUMO gap [61]. As can be seen from Table 4, the magni-
tude of the energy separations between the HOMO and LUMO
are 4.271 eV, 3.951 eV and 4.325 eV for compounds 5a, 5b and
5c, respectively. These large HOMO–LUMO gaps are an indication
of a good stability and a high chemical hardness for the compounds
5a–5c.
bands observed at 3027–2960 cmꢀ1
.
The harmonic vibrational frequencies for compounds 5a–5c
were calculated by using DFT method with 6-31G(d,p) basis set.
Table 5 presents the calculated some selected basic vibrational fre-
quencies and their experimentally measured values. The CH
stretching modes, which were observed at 3027 cmꢀ1, 3000 cmꢀ1
and 2960 cmꢀ1 in the FT-IR spectrums, were calculated as

U.S. Gökßsen et al. / Journal of Molecular Structure 1039 (2013) 71–83
81
Table 5
Comparison of selected experimental and calculated vibrational frequencies (cmꢀ1).
Assigna
5a
5b
5c
Experimental
Calculated
Experimental
Calculated
Experimental
Calculated
m
m
m
m
s(CH)
3027
1763
1669
1609–1574
3065
1763
1669
1574
3000
1765
1672
1617–1592
3065
1821
1713
1601
2960
1771
1681
1613–1589
3081–3064
1821
1702
s(C7@O2)
s(C9@O3)
s(C@C)ring
+
m
s(C@N)
1588
a
m
, stretching.
3065 cmꢀ1, 3065 cmꢀ1 and 3081–3064 cmꢀ1 for compounds 5a, 5b
and 5c, respectively. As can be seen in Table 5, the C9@O3 stretch-
blets between 5.10–5.09 ppm and 5.29–5.22 ppm. The signals for
methoxy and methyl appeared at 3.79–3.71 ppm and 2.38 ppm.
GIAO 1H chemical shift calculations (with respect to TMS) were
performed by the B3LYP method with 6-31G(d,p) basis set. The ob-
tained theoretical results (Table 6) were compared to the experi-
mental 1H chemical shift values. The calculated 1H chemical shift
values (with respect to TMS) are 8.76–3.16 ppm (compound 5a),
8.76–3.23 ppm (compound 5b) and 8.70–2.09 ppm (compound
5c), while the experimental results are obtained to be
7.87–3.22 ppm (compound 5a), 7.87–3.23 ppm (compound 5b)
and 7.75–2.38 ppm (compound 5c). This small differences between
experimental and calculated chemical shifts are due to the used
basis set, solute–solvent interactions and conformational freedom
in the solution.
ing modes, calculated as 1669 cmꢀ1, 1713 cmꢀ1 and 1702 cmꢀ1
;
were observed at 1669 cmꢀ1, 1672 cmꢀ1 and 1681 cmꢀ1 in the
FT-IR spectrums for compounds 5a, 5b and 5c, respectively. These
results obtained by the calculations have shown an adequate con-
sistency with the experimental values. The small differences be-
tween experimental and calculated frequencies are due to the
consideration of the isolated molecules (in gas) in the calculational
method. Therefore, we can conclude that these differences can be
explained by the existence of the intermolecular interactions in
molecular structures of compounds 5a–5c such as CAHꢂ ꢂ ꢂO and
CAHꢂ ꢂ ꢂp.
Multiplet or doublet peaks belong to the protons of aromatic
rings were observed between 7.87 and 6.70 ppm in the 1H NMR
spectrum of the compounds 5a–5c. Three distinct doublet of dou-
blets of the ABX system in the 4,5-dihydro-(1H)-pyrazole ring (a
CH proton and two anisochronous protons of a CH2) appeared at
5.67–3.11 ppm. The CH (Hx) proton appeared between 5.67 and
5.54 ppm due to vicinal coupling with the two magnetically non-
equivalent protons of the methylene group at position 4 of the
4,5-dihydro-(1H)-pyrazole ring. The signals of Ha and Hb of 4,5-
dihydro-(1H)-pyrazole ring were observed as doublet of doublets
in the regions 3.92–3.88 ppm (Hb) and 3.23–3.11 ppm (Ha). The
CH2 protons between the 5-chloro-2-benzoxazolinone and 4,5-
dihydro-(1H)-pyrazole ring resonated as a pair of doublet of dou-
3.4. Biological activity
The synthesized compounds were tested for antibacterial activ-
ity against five bacterial strains including Gram-positive and
Gram-negative, and for antifungal activity against three fungi. Ta-
ble 7 summarizes the antimicrobial activity of the investigated
compounds.
In general, all of the compounds were found to be slightly active
against tested microorganisms. Although there was no significant
activity difference between compounds, compound 5b showed
Table 6
Theoretical and experimental 1H chemical shifts (with respect to TMS, all values in ppm) for the synthesized compounds.
Atom
5a
5b
5c
Experimental
Calculated
Experimental
Calculated
Experimental
Calculated
H2
H4
H5
H8A
H8B
H11A
H11B
H12
H14
H15
H16
H17
H18
H20
H21
H22
7.50–7.52
7.18
7.39
5.29
5.10
3.22
3.92
5.57
7.85–7.87
6.79–6.84
6.79–6.84
6.79–6.84
7.85–7.87
7.50–7.52
7.50–7.52
7.50–7.52
7.25
3.73
3.73
3.73
–
6.69
7.12
7.19
5.31
4.59
3.81
3.16
5.43
8.76
7.80
7.73
7.69
7.51
7.17
7.53
7.17
6.77
4.23
3.84
3.73
–
7.49–7.52
7.18
7.39
5.28
5.09
3.23
3.90
5.54
7.85–7.87
7.49–7.52
7.49–7.52
7.49–7.52
7.85–7.87
6.75
6.88
–
6.82
3.71
3.71
3.71
3.73
3.73
3.73
–
–
–
6.65
7.11
7.18
5.36
4.49
3.80
3.23
5.37
8.76
7.80
7.72
7.70
7.55
7.15
6.76
–
6.71
4.27
3.83
3.80
4.25
3.65
3.75
–
7.48
7.18
7.39
5.22
5.10
3.11
3.88
5.67
7.75
7.32
–
7.32
7.75
6.96–7.02
6.96–7.02
6.70
–
3.74
3.74
3.74
3.79
3.79
3.79
2.38
2.38
2.38
6.65
7.10
7.17
5.34
4.55
3.80
3.11
6.35
8.70
7.68
–
7.44
7.43
7.07
7.35
6.88
–
3.87
3.83
4.29
3.79
4.43
4.50
2.77
2.78
2.09
H24
H25A
H25B
H25C
H26A
H26B
H26C
H27A
H27B
H27C
–
–
–
–
–

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U.S. Gökßsen et al. / Journal of Molecular Structure 1039 (2013) 71–83
Table 7
Minimum inhibitory concentrations (MICs,
lg/mL) of compounds 5a–5c.
MIC (lg/mL)
Compounds
S. aureus (ATCC
29213)
MRSA (ATCC
43300)
E. faecalis (ATCC E. coli (ATCC
P. aeruginosa
(ATCC 27853)
C. albicans (ATCC C. parapsilosis
C. krusei (ATCC
6258)
29212)
25922)
90028)
(ATCC 90018)
5a
5b
5c
1024
1024
1024
1024
512
512
60.25
–
64
16
128
1
512
512
512
0.01
–
512
512
512
1
256
512
512
–
512
512
512
–
256
256
128
–
Ciprofloxacin 0.5
Fluconazole
–
–
–
1
0.5
16
the highest and compound 5c exhibited the lowest antimicrobial
activity for almost all microorganisms.
the 5. position of 4,5-dihydro-(1H)-pyrazole ring. Compound
1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3,4-
dimethoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5b) is found to be
the most active agent against E. faecalis (ATCC 29212). All tested
compounds showed poor antifungal activity against Candida
albicans, Candida krusei and Candida parapsilosis. The data
reported in this article may be a helpful guide for the medicinal
chemist who is working in this area.
All tested compounds displayed highest activity against E. fae-
calis (ATCC 29212). Among the tested compounds, the compound
5b, which has 3,4-dimethoxy substitution on the phenyl in the 5.
position of 4,5-dihydro-(1H)-pyrazole ring, can be considered as
the most active one against E. faecalis (ATCC 29212). Either removal
of 4-methoxy group (compound 5a) or 2-methoxy substitution in-
stead of 4-methoxy (compound 5c) on the phenyl in the 5. position
of 4,5-dihydro-(1H)-pyrazole ring reduced the antibacterial activ-
ity against E. faecalis (ATCC 29212). All compounds showed weak
antibacterial activity when compared to reference drug ciprofloxa-
cin against S. aureus (ATCC 29213), methicillin resistant S. aureus
(ATCC 43300), E. coli (ATCC 25922) and P. aeruginosa (ATCC
27853). Furthermore, it has been indicated that there was no sig-
nificant difference between methicillin resistant and susceptible
strains of S. aureus in terms of antimicrobial activity of compounds.
The newly synthesized compounds showed weak antifungal activ-
ity against C. albicans, C. parapsilosis and C. krusei when compared
to reference drug fluconazole.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.molstruc.2013.
01.066.
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4. Conclusion
1-[2-(5-Chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3-
methoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5a), 1-[2-(5-chloro-2-
benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3,4-dimethoxyphenyl)-4,
5-dihydro-(1H)-pyrazole (5b) and 1-[2-(5-chloro-2-benzoxazoli-
none-3-yl)acetyl]-3-(4-methylphenyl)-5-(2,3-dimethoxyphenyl)-4,
5-dihydro-(1H)-pyrazole (5c) were synthesized and characterized
by elemental analyses, IR, 1H NMR, ESI-MS and single-crystal
X-ray diffraction. The compound 5c has not classical hydrogen
bond while compounds 5a and 5b are linked by intermolecular
CAHꢂ ꢂ ꢂO hydrogen bonds. The comparisons between the calcu-
lated results and the X-ray experimental data indicate that DFT
method shows a good agreement with the experimental results.
The MEP maps show that the negative potential regions are on
oxygen atoms and the positive potential regions are around the
hydrogen atoms. These regions may provide information about
the possible reaction regions for the synthesized structures. The
obtained HOMO and LUMO gaps as 4.271 eV, 3.951 eV and
4.325 eV for compounds 5a, 5b and 5c, respectively show that
the compounds are quite stable in terms of energy and have high
chemical hardness. The small differences between experimental
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