Synthesis, molecular structure and antioxidant activity of (E)-4-[Benzylideneamino]-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one, a Schiff base ligand of 4-aminoantipyrine

Article abstract of DOI:10.1007/s10870-011-0209-1

In this study, the title compound, C₁₈H₁₇N ₃O (M _r = 291.35), was synthesized by the condensation reaction of 4-amino-1,5-dimethyl-2-phenylpyrazole-3-one and benzaldehyde. Single-crystal X-ray diffraction data r

Full text of DOI:10.1007/s10870-011-0209-1

J Chem Crystallogr (2012) 42:93–102
DOI 10.1007/s10870-011-0209-1
ORIGINAL PAPER
Synthesis, Molecular Structure and Antioxidant Activity of (E)-4-
[Benzylideneamino]-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one,
a Schiff Base Ligand of 4-Aminoantipyrine
•
Mohammad Sayed Alam Dong-Ung Lee
Received: 9 March 2011 / Accepted: 17 November 2011 / Published online: 18 December 2011
ꢀ Springer Science+Business Media, LLC 2011
Abstract In this study, the title compound, C18H17N3O
(Mr = 291.35), was synthesized by the condensation
reaction of 4-amino-1,5-dimethyl-2-phenylpyrazole-3-one
and benzaldehyde. Single-crystal X-ray diffraction data
revealed that this compound adopts a trans configuration
around the central C=N double bond. It crystallizes in the
contribution of n ? p* and p ? p* transitions, were
observed in both the experimental and predicted UV–Vis
spectra. A maximum emission band at 370 nm was
observed in the fluorescence spectra of the title compound.
In addition, the title compound showed good DPPH anti-
oxidant activity.
˚
monoclinic, space group P21/c with a = 12.9236(17) A,
˚
˚
b = 6.8349(9) A, c = 17.072(2) A, b = 90.316(3)ꢁ, V =
Keywords Pyrazole-3-ones ꢀ Crystal structure ꢀ Density
functional theory ꢀ Quantum chemical calculation
3
3
˚
1508.0(3) A , Z = 4, Dc = 1.283 Mg/m , F(000) = 616,
l = 0.082 mm-1, R = 0.0442, and wR = 0.0936. Two
different planes exist within the molecule; e.g. the pyraz-
olone and benzylidene groups attached to C9 of the pyr-
azolone ring are almost coplanar, whereas the phenyl group
attached to the N1 of the pyrazolone ring is in another
plane. Density functional theory (DFT) and time-dependent
DFT calculations were performed to predict the electronic
structure and absorption spectra of (E)-4-[benzylidenea-
mino]-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one, a schiff
base ligand of 4-aminoantipyrine using B3LYP/6-311G
basis set on the AM1 optimized geometry. The predicted
vibrational frequencies using the B3LYP/6-311G method
were in strong agreement with the experimental IR spectra.
The time dependent DFT calculations were used to eval-
uate the electronic absorption spectrum and three electron
transition bands, which were mainly derived from the
Introduction
In the last few decades, Schiff base compounds have
received much attention in the field of chemistry and
biology due to their chemotherapeutic value [1–3]. Schiff
base compounds have also been used as effective ligands
for metal ions in the preparation of dyes, liquid crystals and
powerful corrosion inhibitors. 4-Amino-1,5-dimethyl-2-
phenylpyrazole-3-one (4-aminoantipyrine) forms a variety
of Schiff bases with aldehydes and their transition metal
complexes showed a wide range of biological activities and
applications [4–6].
Free radicals including reactive oxygen species (ROS)
cause oxidative stress in biological systems. Antioxidants
have been shown to play an important role in protecting
humans against many fatal diseases. Antioxidants have
been widely used in medicine and different fields of
industry to interrupt radical-chain oxidation processes,
improve general health, help cell rejuvenation and prevent
cancer [7]. Quantum-chemical parameters have been used
to help describe the properties of antioxidant substances in
detail. Density functional theory (DFT) has received much
interest as a reliable standard tool for the quantum chem-
ical calculation of molecular structures and biological
M. S. Alam (&) ꢀ D.-U. Lee (&)
Division of Bioscience, Dongguk University, Gyeongju 780-714,
Republic of Korea
e-mail: alam_sms@dongguk.ac.kr; alam_sms@yahoo.com
D.-U. Lee
e-mail: dulee@dongguk.ac.kr
M. S. Alam
Department of Chemistry, Jagannath University,
Dhaka 1100, Bangladesh
123

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J Chem Crystallogr (2012) 42:93–102
properties of molecule. In recent years, DFT has been
extensively used to study the structures and absorption
spectra of different classes of compounds [8–11]. DFT
studies can provide useful information in regards to the
coordination properties of ligands. A remarkable number of
Schiff base ligands of 4-aminoantipyrine have recently
been reported [12–17] but their quantum chemistry calcu-
lation have not yet been studied. In the present study,
we report the molecular structure, spectral properties
and antioxidant activity of (E)-4-[benzylideneamino]-1,
5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one, a Schiff base
derivative of 4-aminoantipyrine, which will provide useful
information to explain the coordination properties of the
Schiff bases of aminoantipyrine.
give the pure compound with a yield of 85%, m.p. 178.3 ꢁC.
Single yellow crystals of the title compound suitable for
X-ray analysis were obtained by slow evaporation of an
ethanol solution. The constitution of 4-[benzylideneamino]-
1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one was supported
by 1H NMR, 13C NMR, IR and HRMS analysis.
1H NMR (200 MHz, CDCl3): d 2.49 (s, 3H, =C–CH3),
3.14 (s, 3H, –N–CH3), 7.31–7.52 (m, 8H, ArH), 7.84–7.89
(m, 2H, ArH), 9.77 (s, 1H, –N=CH). 13C NMR (62.5 MHz,
CDCl3): d 10.91, 35.83, 110.30, 125.15, 129.60, 127.51,
128.00, 128.70, 130.32, 134.90, 138.11, 150.30, 160.79,
163.38. HRMS-FAB (m/z): [M ? H]? calculated for
C18H17N3O, 292.1338; found 292.1339 (error: ?0.4 ppm).
Crystal Structure Determination
Experimental Section
The solvent loss technique was used to grow yellow plate-
shaped crystals of the title compound. A single crystal of
suitable size (0.29 mm 9 0.16 mm 9 0.07 mm) was cho-
sen for the X-ray diffraction studies. The data were collected
at a temperature of 200(2) K on a Bruker SMART CCD area
detector diffractometer [18] with graphite monochromated
General
The melting point was determined using a Stuart SMP3
apparatus and was uncorrected. The 1H and 13C NMR
spectra were recorded using TMS as a reference standard in
CDCl3 solvent on a Varian GEMINI 200 spectrophotometer.
FT-IR spectra, as KBr pellets, were obtained using a Bruker
Tensor 37 spectrophotometer. Electronic absorption spectra
were measured on a Varian Cary 4000 spectrophotometer in
an EtOH solution and fluorescence spectra were measured
on Varian Cary Eclipse Fluorescence spectrophotometer.
FAB-MS spectra were acquired using a Jeol JMS-700 mass
spectrometer. Crystal data collection: Bruker SMART; cell
refinement: Bruker SAINT; data reduction: Bruker SAINT;
program(s) used to solve structure: Bruker SHELXTL;
program(s) used to refine the structure: Bruker SHELXTL;
molecular graphics: Bruker SHELXTL. Absorbance for
antioxidant activity was measured on Optizen 2120 UV/VIS
Spectrophotometer (Mecasys Co. Ltd., Korea).
˚
radiation MoKa (k = 0.71073 A). A total of 20,373 reflec-
tions were collected, of which 3,758 (-17 B h B 17,
-9 B k B 9, -22 B l B 22) were treated as observed. The
structure was solved by direct methods using SHELXTL
[19, 20]. Full-matrix least-squares refinement using SHEL-
XTL with isotropic displacement parameters for all the non
hydrogen atoms converged the residual to R1 = 0.1676.
Subsequent refinements [21] were carried out with aniso-
tropic thermal parameters for the non-hydrogen atoms. The
hydrogen atoms were fixed at chemically acceptable posi-
tions and were allowed to ride on their parent atoms, with a
˚
C–H distance of 0.9500–0.9800 A. The final refinement
converged to R = 0.0442, wR = 0.0936, w = 1/[s2(Fo)2 ?
(0.0633P)2 ? 0.00P], where P = (Fo2 ? 2F2c)/3), S = 0.755,
(D/r)max \ 0.001, (Dq)max = 0.207 and (Dq)min
=
-3
˚
-0.262 e A
.
Synthesis and Crystallization
An anhydrous ethanol solution (10 mL) of 4-amino-1,
5-dimethyl-2-phenylpyrazol-3-one (203 mg, 1 mmol) was
added to an anhydrous ethanol solution (10 mL) of benzal-
dehyde (106 mg, 1 mmol) and the mixture was refluxed at
80 ꢁC for 4 h under atmospheric conditions (Scheme 1). The
precipitate formed was collected by filtration and purified by
recrystallization from ethanol, and then dried in vacuo to
Quantum Chemical Calculations
The molecular geometries of the title compound were
optimized using MM? molecular modeling and semi-
empirical molecular orbital AM1 methods [22]. The DFT
calculations with a hybrid functional B3LYP (Becke’s
three parameter nonlocal exchange functional along with
Scheme 1 Synthesis of (E)-4-
[benzylideneamino]-1,5-
dimethyl-2-phenyl-1H-pyrazol-
3(2H)-one
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J Chem Crystallogr (2012) 42:93–102
95
the Lee–Yang–Parr correlation functional) [23, 24] at basis
set 6-311G were then performed using the GAMESS
(version March 25, 2010 R2) software package [25]. No
imaginary frequencies were obtained in the vibrational
frequencies calculations indicating that the structures were
stable. After optimization, Muliken charge and properties
of frontier molecular orbitals (FMOs) of the title compound
were analyzed using the results calculated at the B3LYP/
6-311G level.
Table 1 Crystal data and structure refinement for (E)-4-[benzylide-
neamino]-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one
Empirical formula
Formula weight
Temperature
C18H17N3O
291.35
200(2) K
˚
0.71073 A
Wavelength
Crystal system
Space group
Monoclinic
P21/c
Hall symbol
-P 2ybc
˚
a = 12.9236(17) A
Unit cell dimensions
˚
b = 6.8349(9) A
DPPH Radical Scavenging Activity
˚
c = 17.072(2) A
The free radical-scavenging activity of the title compound
was assayed according to the Blois method with some
modification [26] using 1,1-diphenyl-2-picrylhydrazyl
(DPPH). 0.1 mL of different concentrations (2.5–20 mg/
mL) of sample in ethanol were added to 4 mL of a
1.5 9 10-5 M DPPH solution and mixed thoroughly. The
solution was then left to stand at room temperature in the
dark. After 30 min of incubation, the absorbance of
the solution was measured at 520 nm and the antioxidant
activity was calculated using the following equation:
b = 90.316(3)ꢁ
1508.0(3) A
3
˚
Volume
Z
4
Density (calculated)
Absorption coefficient
F(000)
1.283 Mg/m3
0.082 mm-1
616
0.29 9 0.16 9 0.07 mm3
Crystal size
Theta range for data collection
Index ranges
1.58 to 28.34ꢁ
-17 B h B 17, -9 B k B 9,
-22 B l B 22
Reflections collected
20,373
DPPH radical-scavenging activity %
ÂÀ
Independent reflections
Completeness to theta = 28.34ꢁ
Absorption correction
Refinement method
3758 [R(int) = 0.1319]
99.9%
¼
Absorbance of the control
Áꢀ
ꢁ Absorbance of the sample
None
Full-matrix least-squares on F2
Ã
Absorbance of the control ꢂ 100
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I [ 2r(I)]
R indices (all data)
3758/0/201
0.755
Results and Discussion
R1 = 0.0442, wR2 = 0.0936
R1 = 0.1602, wR2 = 0.1626
Synthesis and Structural Description
-3
˚
0.207 and -0.262 e A
Largest diff. peak and hole
The title compound was synthesized in good yield using a
condensation reaction of 4-amino-1,5-dimethyl-2-phe-
nylpyrazole-3-one with benzaldehyde as shown in Scheme 1.
The chemical structure of the synthesized compound was
confirmed by spectroscopic methods, and the exact stereo-
chemistry was determined by X-ray crystal analysis.
˚
planar, with an r.m.s. deviation for fitted atoms of 0.0337 A,
and a dihedral angle of 67.04ꢁ with its attached phenyl ring
(C1–C6). Torsion angles of N2–N1–C1–C6 and N2–N1–
C1–C2 were -150.7(2) and 32.6(5)ꢁ, respectively. The
atom O1 only slightly deviated from the pyrazolone mean
plane, with torsion angles value of C10–C9–C8–O1 and
N2–N1–C8–O1 are 175.2(3) and -171.0(2)ꢁ, respectively.
The C7 and C11 atoms were located on the opposite side of
the pyrazolone plane and the torsion angle of C11–C10–
N2–C7 was -24.3(4)ꢁ. Due to conjugation through the
imino double bond C12=N3, the pyrazolone and the C13–
C18 phenyl were approximately coplanar, with a dihedral
angle between them of 3.9ꢁ. The torsion angles value of
C10–C9–N3–C12, C8–C9–N3–C12, C13–C12–N3–C9,
C14–C13–C12–N3 and C18–C13–C12–N3 were -179.2(3),
-8.7(4), 176.1(2), 2.9(4) and -176.7(3)ꢁ, respectively. The
packing arrangement in the crystal structure of (E)-4-
[benzylideneamino]-1,5-dimethyl-2-phenyl-1H-pyrazol-
3(2H)-one are shown in Fig. 2, with intermolecular and
Details of the X-ray diffraction crystal data and structure
refinement for the title compound are shown in Table 1. The
title compound crystallized in the monoclinic, space group
˚
P21/c with a = 12.9236(17) A, b = 6.8349(9) A, c =
˚
3
˚
˚
17.072(2) A, b = 90.316(3)ꢁ, V = 1508.0(3) A , Z = 4,
Dc = 1.283 Mg/m3, F(000) = 616, l = 0.082 mm-1, R =
0.0442, and wR = 0.0936. Bond lengths and angles of all
the non-hydrogen atoms of 4-[benzylideneamino]-1,
5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (Table 2) were
within normal ranges [27]. The ORTEP diagram of the
molecule is shown in Fig. 1a, with thermal ellipsoids drawn
at a 50% probability. The geometry was calculated using
software (Bruker SHELXTL). As shown in Fig. 1a, the
pyrazolone ring (C8–C10/N1/N2/N3/O1) was almost
123

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J Chem Crystallogr (2012) 42:93–102
˚
Table 2 Selected bond lengths (A) and angles (ꢁ) by X-ray and
theoretical calculations for (E)-4-[benzylideneamino]-1,5-dimethyl-2-
phenyl-1H-pyrazol-3(2H)-one at B3LYP/6-311G level of theory
Table 2 continued
Exp.
Calc.
N(2)–C(10)–C(11)
C(9)–C(10)–C(11)
C(12)–N(3)–C(9)
122.0(3)
127.6(3)
121.6(2)
120.6(3)
118.9(3)
119.9(3)
121.2(3)
120.4(3)
120.4(3)
119.8(3)
120.3(3)
120.1(3)
121.6
127.7
121.4
121.6
119.0
118.3
122.7
120.3
120.3
119.9
119.9
120.6
Exp.
Calc.
˚
Bond lengths (A)
C(1)–C(6)
1.382(4)
1.384(4)
1.420(3)
1.389(4)
1.378(4)
1.379(4)
1.378(4)
1.405(3)
1.406(3)
1.353(3)
1.463(3)
1.237(3)
1.436(4)
1.369(4)
1.394(3)
1.485(4)
1.285(3)
1.469(4)
1.382(4)
1.393(4)
1.376(4)
1.373(4)
1.372(4)
1.392(4)
1.406
N(3)–C(12)–C(13)
C(18)–C(13)–C(14)
C(18)–C(13)–C(12)
C(14)–C(13)–C(12)
C(15)–C(14)–C(13)
C(16)–C(15)–C(14)
C(17)–C(16)–C(15)
C(16)–C(17)–C(18)
C(13)–C(18)–C(17)
C(1)–C(2)
1.405
1.441
1.397
1.395
1.397
1.393
1.441
1.426
1.391
1.481
1.255
1.455
1.372
1.395
1.490
1.299
1.464
1.407
1.408
1.393
1.402
1.398
1.395
C(1)–N(1)
C(2)–C(3)
C(3)–C(4)
C(4)–C(5)
C(5)–C(6)
N(1)–N(2)
N(1)–C(8)
N(2)–C(10)
N(2)–C(7)
C(8)–O(1)
intramolecular hydrogen bonding interactions. The hydro-
gen-bond geometry are shown in Table 3. Weak non-clas-
sical intermolecular C–HꢀꢀꢀO and C–HꢀꢀꢀN hydrogen bonds
stabilized the crystal packing of title compound. An intra-
molecular C–HꢀꢀꢀO hydrogen-bonding interaction is also found,
which helps to stabilize the conformation of the molecule.
C(8)–C(9)
C(9)–C(10)
C(9)–N(3)
C(10)–C(11)
N(3)–C(12)
C(12)–C(13)
C(13)–C(18)
C(13)–C(14)
C(14)–C(15)
C(15)–C(16)
C(16)–C(17)
C(17)–C(18)
Bond angles (ꢁ)
C(6)–C(1)–C(2)
C(6)–C(1)–N(1)
C(2)–C(1)–N(1)
C(1)–C(2)–C(3)
C(4)–C(3)–C(2)
C(3)–C(4)–C(5)
C(6)–C(5)–C(4)
C(5)–C(6)–C(1)
N(2)–N(1)–C(8)
N(2)–N(1)–C(1)
C(8)–N(1)–C(1)
C(10)–N(2)–N(1)
C(10)–N(2)–C(7)
N(1)–N(2)–C(7)
O(1)–C(8)–N(1)
O(1)–C(8)–C(9)
N(1)–C(8)–C(9)
C(10)–C(9)–N(3)
C(10)–C(9)–C(8)
N(3)–C(9)–C(8)
N(2)–C(10)–C(9)
DFT Calculations
The optimized geometric parameters obtained from the
DFT-B3LYP/6-311G calculations of the title compound
are listed in Table 2. The theoretical geometric structure of
the molecule is shown in Fig. 1b. Comparisons between the
experimental bond lengths and the calculated bond lengths
indicated that all optimized bond lengths were slightly
larger than the experimental values. This was the case
because the experimental data was collected in the solid
phase, whereas the calculated values corresponded to the
isolated molecule in gas phase. The highest bond length
120.6(3)
117.3(3)
122.0(3)
119.1(3)
120.2(3)
120.1(3)
120.2(3)
119.6(3)
108.7(2)
119.5(2)
122.1(2)
107.3(2)
126.0(2)
119.0(2)
123.0(3)
131.9(3)
105.0(2)
121.9(3)
107.9(2)
129.6(3)
110.4(3)
118.7
119.1
122.1
120.3
120.8
118.9
121.0
120.2
107.9
120.4
124.2
107.2
121.2
118.6
124.6
129.2
106.2
123.3
108.1
128.5
110.6
˚
difference was 0.038 A for the N2–C10 bond, whereas the
biggest bond angle deviation occurred in the C10–N2–C7
angle (4.8ꢁ). There are two probable reasons for the above
discrepancies: the calculated data were for the molecule in
a gas phase and no molecular interactions were considered,
whereas the experimental data was acquired in the solid
state and crystal field interactions were present. The
geometry of the molecule in the solid state was subject to
various intermolecular interactions, e.g. van der Waals
forces, crystal packing forces and hydrogen-bond interac-
tions [28]. Another reason for this discrepancy is that in the
solid state, there exist intermolecular hydrogen bond
interactions between N2 and H11 and steric hindrance
between the two methyl groups attached to N2 and C10,
while in the theoretical calculations, the interactions were
neglected, which, to some extent, may have led to a higher
bond angle of C10–N2–C7 in the solid state. Despite these
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J Chem Crystallogr (2012) 42:93–102
97
˚
Table 3 Hydrogen-bond geometry (A, ꢁ)
˚
˚
˚
D–HꢀꢀꢀA
D–H (A) HꢀꢀꢀA (A) DꢀꢀꢀA (A) D–HꢀꢀꢀA (ꢁ)
C7–H7aꢀꢀꢀO1i
0.98
2.67
2.61
3.04
3.482
3.332
3.687
139.9
126.7
124.1
C18–H18ꢀꢀꢀO1ii
0.95
C11–H11aꢀꢀꢀN2iii 0.98
Symmetry codes: (i) x, -y ? 1/2, z - 3/2; (ii) -x ? 1, y - 1/2,
-z ? 3/2; (iii) x, y - 1, z
D donor atom, H hydrogen atom, A acceptor atom
Vibrational Frequencies
Figure 3 shows the comparison between the experimental
and the virtual infrared spectra, where the calculated fre-
quencies are plotted against intensity. The vibrational fre-
quencies were predicted using the B3LYP/6-311G level of
the theory at a spin multiplicity of one and the GAMESS
(version March 25, 2010 R2) software package [25] was
used to assign the calculated harmonic frequencies. Some
primary calculated harmonic frequencies and their
description concerning the assignment are listed in Table 4.
According to the results presented in Table 4 and Fig. 3,
the differences between the experimental and predicted
frequencies were relatively small. Therefore, the DFT-
B3LYP/6-311G method used in the present study can
accurately predict the vibrational frequencies of the title
compound.
Fig. 1 a The molecular structure of (E)-4-[benzylideneamino]-1,5-
dimethyl-2-phenyl-1H-pyrazol-3(2H)-one, showing 50% probability
displacement ellipsoids and the atom-numbering scheme. b The
theoretical geometric structure of (E)-4-[benzylideneamino]-1,5-
dimethyl-2-phenyl-1H-pyrazol-3(2H)-one
some differences, the aforementioned comparisons suggest
that the DFT-B3LYP/6-311G method [29] can produce
satisfactory precision and reproduce the crystal structure of
the title compound, which are the bases for our following
discussion.
Fig. 2 Packing arrangement in
the crystal structure of (E)-4-
[benzylideneamino]-1,5-
dimethyl-2-phenyl-1H-pyrazol-
3(2H)-one. Dashed lines
indicate hydrogen bonds
123

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J Chem Crystallogr (2012) 42:93–102
Fig. 3 Experimental IR spectra
(top) and simulated IR spectra at
the B3LYP/6-311G level of the
theory (bottom) for the title
compound
FMOs were calculated according to the quantum chemical
calculations and in the calculation, 35 atoms, which
involved 337 basis functions including 77 occupied orbi-
tals, were shown to be involved.
Table 4 Comparison of some experimental and calculated vibra-
tional spectra of the title compound
Assignments
Exp.
Calc.
(B3LYP/
6-311G)
According to the molecular orbital theory, the HOMO-
LUMO and the vicinal molecular orbitals are involved in
the coordination property of a molecule and the molecular
stability depends on the negative energy values of the
FMOs [30]. The energy levels of the HOMO-2, HOMO-1,
HOMO, LUMO?1 and LUMO?3 orbitals computed at the
B3LYP/6-311G level for the title compound are shown in
Fig. 4. The energy of HOMO and LUMO and the energy
differences were -9.14, -5.52 and 3.62 eV, respectively.
The total energy (-1035 a.u.) of the title compound was
lower and the energies of HOMO and LUMO and their
neighboring orbitals were all negative, which indicates that
the title compound was stable. The HOMO and its vicinal
orbital play the role of electron donors, and the LUMO and
its vicinal orbital play the role of electron acceptors.
Based on the optimized structure of the title compound,
the Mulliken charge distribution of all atoms was calcu-
lated and the results are given in Table 5. This analysis
indicated that the atomic electro negativity plays an
important role in the Mulliken charge distribution. Namely,
between the two connecting atoms, the atom having a
higher electronegativity will carry negative charges, while
the atom having a lower electronegativity will carry posi-
tive charges [28]. Thus, for the title compound, H and C
C–H str. in phenyl ring
C–H str. in methyl group
[C=O functional group
3,054
2,937
1,651
3,215–3,177
3,045
1,666
C=N str. and C–C def. in phenyl ring 1,597–1,566 1,568–1,538
C–H def. in phenyl ring
C–H def. in methyl group
C–O str. in carbonyl group
N–N str. and all C–H def.
N–N str. and all C–N str.
All of the C–H def.
1,488
1,372
1,302
1,132
1,062
884
1,457
1,318
1,248
1,117
1,046
907
Molecular skeleton def.
C–C def. in phenyl ring
C–H def. in phenyl ring
Molecular skeleton def.
830
853
760
791
698
721
597
581
str stretching, def deformation
Energy of FMOs and Mulliken Charge Distribution
The FMOs play an important role in determining the
reactivity and ability of a molecule to absorb light. These
FMOs are important for the optical and electric properties
and molecular reactivity. The single point energy and
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J Chem Crystallogr (2012) 42:93–102
99
Table 5 Mulliken charges
(e) for the title compound
Atom
Charge/e
O(1)
-0.437
-0.610
-0.400
-0.358
0.284
N(1)
N(2)
N(3)
C(1)
C(2)
-0.133
-0.174
-0.122
-0.169
-0.130
-0.394
0.645
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
-0.203
0.453
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
H(2)
-0.584
-0.070
-0.060
-0.051
-0.175
-0.123
-0.167
-0.143
0.173
Fig. 4 Contour plots and energy of some frontier molecular orbitals
in the title compound
(non-bonding with H atoms) were all positive, while N
(from pyrrole ring and imine), O (bonding with C) and C
(bonding with H) were all negative. Therefore, the hetero
atoms, e.g. O1, N1, N2 and N3, bearing the negative charge
could act as an electron donor when coordinating with
metals except C7 and C11. According to the Mulliken
charge distribution, these two atoms also have relatively
large negative values and might not be involved in coor-
dination with metals due to the steric hindrance between
the C7 and C11 methyl groups. The crystal structure of the
title compound also revealed that the two methyl groups
were located opposite to the pyrazolone ring due to steric
hindrance. The HOMO contour plot (Fig. 4) of the title
compound shows that the electron density around the C7
and C11 atoms was much lower than O1, N1, N2 and N3
atoms, which resulted in a lack of electron donor capacity
of the former two atoms.
H(3)
0.146
H(4)
0.153
H(5)
0.152
H(6)
0.224
H(7A)
H(7B)
H(7C)
H(11A)
H(11B)
H(11C)
H(12)
H(14)
H(15)
H(16)
H(17)
H(18)
0.203
0.221
0.218
0.238
0.203
0.207
0.206
0.167
0.148
0.150
0.149
0.164
UV-Absorption Spectra
Experimental electronic absorption spectra were measured
in an ethanol solution at room temperature and theoretical
electronic absorption spectra were predicted using the TD-
DFT method based on the B3LYP/6-311G level optimized
structure of the title compound. The calculated and
experimental electronic spectrums are shown in Fig. 5.
Table 6 represents the most important calculated electronic
transition models of the title compound. As shown in Fig. 5
and Table 6, both the experimental and calculated data
showed the presence of three bands with some discrepan-
cies. The difference between the experimental values and
predicted values may be due to the following reasons: The
TD-DFT approach is based on the random-phase approxi-
mation (RPA) method [31] and spin–orbit splitting is not
considered in the calculation; the values are averaged. In
our study, the electronic structure was evaluated by direct
electronic excitations and only singlet–singlet transitions
were considered. In addition, the role of the ethanol solvent
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J Chem Crystallogr (2012) 42:93–102
Fig. 6 Fluorescence spectra of the title compound
Fig. 5 Experimental and calculated electronic absorption spectra of
the title compound
Table 7 Free radical scavenging activity of title compound observed
with DPPH assay
Table 6 Experimental and calculated electronic absorption spectra
values
Sample
Conc.
(mg/ml)
%
Inhibition
IC50
(lM)
Exp.
Calc. (TD-DFT)
20
92.78
85.45
53.65
28.22
15.56
96.52
96.52
49
31.26
Wave
length (nm)
Wave
length (nm)
Oscillator
strength
Electronic transition
15
10
236
255
328
224
241
343
0.2709
0.1905
0.5802
HOMO ? LUMO?3
HOMO-2 ? LUMO
HOMO ? LUMO?1
HOMO-1 ? LUMO
HOMO ? LUMO
5
2.5
Ascorbic acid
0.25
0.125
0.0625
0.0312
0.0156
0.41
29.6
12.4
was not considered in the theoretical calculation. Figure 4
shows counter plots and the energy of some selected FMOs
active in the electronic transitions. Based on the B3LYP/6-
311G optimized geometry, the natural population analysis
indicates that the occupied and unoccupied orbitals were
mainly composed of p atomic orbitals. As shown in Fig. 4
and Table 6, the electrons are transferred between the two
phenyl ring and pyrazolone ring, which corresponds to the
n ? p* and p ? p* electronic transition.
The title compound displayed strong antioxidant activity
with an IC50 value of 31.26 lM. Ascorbic acid, a phenolic
antioxidant has been used as a positive control which
showed stronger antioxidant activity (IC50 value of
0.41 lM) than that of the title compound. The mechanism
of phenolic antioxidants is well known. However, there has
been an increase in interest in understanding and charac-
terizing the mechanism of non phenolic antioxidants. Thus,
it would be interesting to examine the relationship between
the electrochemical properties and molecular structures of
antioxidants. Table 5 shows that a high electron density
was located near the –N1–N2– (-0.610, -0.400) and –C9–
N3– (-0.203, -0.358) bonds. This finding implies that
these atom groups may be subject to oxidation. The
carbons of two methyl groups, C11 (-0.584) and –C7–
(-0.394) also bear a high electron density and may pro-
duce proton free radicals to neutralize the DPPH (Fig. 7).
However, the radical formed from the title compounds was
not sufficiently stabilized through resonance; thus, many
Fluorescence Spectra
The fluorescence spectrum was measured in an ethanol
solution to determine the fluorescence property of the title
compound (Fig. 6). A maximum emission band at 370 nm
was observed in the spectrum, indicating that the title
compound has no potential fluorescence property.
Antioxidant Activity
The DPPH antioxidant assay was performed using the
Blois method and the results are presented in Table 7.
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J Chem Crystallogr (2012) 42:93–102
101
Fig. 7 Proposed mechanism for
the DPPH• reaction
different reactions are possible. To support our proposed
reaction mechanism, it would be interesting to characterize
the reaction products using liquid chromatograph coupled
with a mass spectrometer.
from: Cambridge Crystallographic Data Center (CCDC),
12 Union Road, Cambridge CB2 1EZ, UK; fax: ?44(0)
1222-336033; e-mail: deposit@ccdc.cam.ac.uk; www.ccdc.
cam.ac.uk/data_request/cif.
Conclusions
References
In this study, we synthesized a single crystal of a Schiff base
ligand of 4-amino-1,5-dimethyl-2-phenylpyrazole-3-one
using a condensation reaction with benzaldehyde. X-ray
diffraction analysis reveals that the structure of (E)-4-
[benzylideneamino]-1,5-dimethyl-2-phenyl-1H-pyrazol-3
(2H)-one had monoclinic (P21/c) symmetry and a trans
configuration around the central C=N double bond. The unit
cell of the molecular packing was composed of four mol-
ecules and formed inversion related dimmers. The opti-
mized geometries and electronic structures of the title
compound using B3LYP/6-311G calculations revealed a
close relation with the crystal structure. The comparison
between the experimental and predicted data indicates that
the 6-311G basis set at a density functional B3LYP level
can be used to accurately predict the vibrational frequen-
cies. UV–Vis absorption spectra were simulated using
TD-DFT calculations. The NBO analyses suggest that the
electronic spectra were mainly due to the n ? p* and
p ? p* electronic transition. The DPPH antioxidant
activity of the title compound might be due to the formation
of proton free radicals by the C7 or C11 methyl groups.
1. Ali MA, Mirza AH, Butcher RJ, Tarafder MTH, Keat TB, Ali
AM (2002) J Inorg Biochem 92:141–148
2. Cukurovali A, Yilmaz I, Ozmen H, Ahmedzade M (2002) Transit
Met Chem 27:171–176
3. Santos MLP, Bagatin IA, Pereira EM, Ferreira AMDC (2001)
J Chem Soc Dalton Trans 838–844
4. Ismail KZ (2000) Transit Met Chem 25:522–528
5. Abd Rehim SS, Ibrahim MAM, Khalid KF (2001) Mater Chem
Phys 70:268–273
6. Yadav PN, Demertzis MA, Kovala-Demertzi D, Skoulika S, West
DX (2003) Inorg Chim Acta 349:30–36
7. Forest SE, Stimson MJ, Simon JD (1999) J Phys Chem B103:
3963–3965
8. Nazeeruddin MK, Angelis FD, Fantacci S, Selloni A, Viscardi G,
¨
Liska P, Ito S, Takeru B, Gratzel M (2005) J Am Chem Soc
127:16835–16847
9. Xu J, Zhang H, Wang L, Liang G, Wang L, Shen X, Xu W (2010)
Monatsh Chem 141:549–555
10. Lee C, Sohlberg K (2010) Chem Phys 367:7–19
11. Ji N-N, Shi Z-Q, Zhao R-G, Zheng Z-B, Li Z-F (2010) Bull
Korean Chem Soc 31:881–886
12. Zhao W-N (2007) Acta Crystallogr E63:m2095
´
13. Montalvo-Gonzalez R, Ariza-Castolo A (2003) J Mol Struct
655:375–389
14. Li Z-X, Zhang X-L (2006) Chin J Struct Chem 25:29–32
15. Hu T-P (2006) Acta Crystallogr E62:o2270–o2271
16. Zhang Q-Z, Zhao Y-L, Chen X, Yu M (2006) Acta Crystallogr
E62:o5252–o5254
Supplementary Material
17. Liu S-X, Han J-R, Zhen X-L, Tian X (2006) Acta Crystallogr
E62:o5765–o5766
18. Bruker (2000) SMART (version 5.625) for Windows NT. Bruker
AXS Inc., Madison
19. Sheldrick GM (2008) Acta Crystallogr A64:112–122
20. Sheldrick GM (2008) SHELXTL. Version 6.12 for Windows NT.
Bruker AXS Inc., Madison
Crystallographic data for the structure of the title com-
pound have been deposited in the Cambridge Crystallo-
graphic Data Center (Deposition number CCDC-783980).
The data can be obtained, free of charge, upon request
123

102
J Chem Crystallogr (2012) 42:93–102
21. Bruker (2000) SAINT (version 5.625) for Windows NT. Bruker
AXS Inc., Madison
22. Dewar MJS, Zoebisch EG, Healy EF (1985) J Am Chem Soc
107:3902–3909
23. Becke AD (1993) J Chem Phys 98:5648–5652
24. Lee C, Yang W, Parr RG (1988) Phys Rev B 37:785–789
25. Schmidt MW, Baldridge KK, Boatz JA, Elbert ST, Gordon MS,
Jensen JH, Koseki S, Matsunaga N, Nguyen KA, Su S, Windus
TL, Dupuis M, Montgomery JA Jr (1993) J Comput Chem
14:1347–1363
26. Blois MS (1958) Nature 181:1199–1200
27. Allen FH, Kennard O, Watson DG, Brammer L, Orpen AG,
Taylor R (1987) J Chem Soc Perkin Trans II S1–S19
28. Zhao PS, Shao DL, Zhang J, Wei Y, Jian FF (2009) Bull Korean
Chem Soc 30:1667–1670
29. Jian FF, Zhao PS, Yu Q, Wang QX, Jiao K (2004) J Phys Chem A
108:5258–5267
30. Xia SW, Xu X, Sun YL, Fan YH, Bi CF, Zhang DM, Yang LR
(2006) Chin J Struct Chem 25:197–203
31. Mendizabal F, Olea-Azar C (2005) Int J Quant Chem 103:34–44
123