Crystal structure and DFT calculations of 5-(4-Chlorophenyl)-1-(6- methoxypyridazin-3-yl)-1H-pyrazole-3-carboxylic acid

Article abstract of DOI:10.1016/j.saa.2014.05.014

The title compound, 5-(4-Chlorophenyl)-1-(6-methoxypyridazin-3-yl)-1H- pyrazole-3-carboxylic acid, has been characterized by using elemental analysis, MS, FT-IR, ¹H NMR and ¹³C NMR spectroscopic, and crystallographic techniques. The title compound crystallizes in the triclinic space group P-1 with a = 9.612(1), b = 9.894(1), c = 17.380(1) ?, α = 90.213(5)°, β = 104.99(1)°, γ = 111.072(5)°, V = 1481.3(2) ?³ and D_x = 1.483 g cm^-3 respectively. The structure of the compound has also been examined by using quantum chemical methods. The molecular geometry and vibrational frequencies of monomeric and dimeric form of the title compound in the ground state have been calculated by using the B3LYP/6-31G(d,p) level of the theory. The calculated results show that the optimized geometry and the theoretical vibration frequencies of the dimeric form are good agreement with experimental data. In addition, HOMO-LUMO energy gap, molecular electrostatic potential map, thermodynamic properties of the title compound were performed at B3LYP/6-31G(d,p) level of theory.

Full text of DOI:10.1016/j.saa.2014.05.014

Accepted Manuscript
Crystal structure and DFT calculations of 5-(4-Chlorophenyl)-1-(6-methoxy-
pyridazin-3-yl)-1H-pyrazole-3-carboxylic acid
Can Alaşalvar, Mustafa Serkan Soylu, Hüseyin Ünver, Nazan Ocak İskeleli,
Mustafa Yildiz, Murat Çiftçi, Erden Banoğlu
PII:
S1386-1425(14)00777-X
http://dx.doi.org/10.1016/j.saa.2014.05.014
SAA 12168
DOI:
Reference:
Spectrochimica Acta Part A: Molecular and Biomo-
lecular Spectroscopy
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Revised Date:
Accepted Date:
27 March 2014
30 April 2014
9 May 2014
Please cite this article as: C. Alaşalvar, M.S. Soylu, H. Ünver, N.O. İskeleli, M. Yildiz, M. Çiftçi, E. Banoğlu, Crystal
structure and DFT calculations of 5-(4-Chlorophenyl)-1-(6-methoxypyridazin-3-yl)-1H-pyrazole-3-carboxylic
acid, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy (2014), doi: http://dx.doi.org/10.1016/
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Crystal structure and DFT calculations of
5-(4-Chlorophenyl)-1-(6-methoxypyridazin-3-yl)-1H-pyrazole-3-carboxylic
acid
Can Alaşalvara,*, Mustafa Serkan Soylub, Hüseyin Ünverc, Nazan Ocak İskelelid, Mustafa
Yildize, Murat Çiftçif, Erden Banoğluf
aGiresun University, Technical Science Vocational High School, Department of Electric and energy, TR-
28100,Giresun Turkey
bDepartment of Physics, Giresun University, TR-28100 Giresun, Turkey
cDepartment of Physics, Faculty of Science, Ankara University, TR-06100 Tandoğan, Ankara, Turkey
dDepartment of Science Education, Ondokuz Mayıs University, TR-55200 Atakum, Samsun, Turkey
eDepartment of Chemistry, Faculty of Science and Arts, Çanakkale Onsekiz Mart University, TR-17100
Çanakkale, Turkey
fGazi University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, TR-06100 Besevler, Ankara,
Turkey
ABSRACT
The title compound, 5-(4-Chlorophenyl)-1-(6-methoxypyridazin-3-yl)-1H-pyrazole-3-
carboxylic acid, has been characterized by using elemental analysis, MS, FT-IR, 1H-NMR and
13C-NMR spectroscopic, and crystallographic techniques. The title compound crystallizes in
the triclinic space group P-1 with a = 9.612(1), b = 9.894(1), c = 17.380(1) Å, α= 90.213(5)°,
 = 104.99(1)°, γ = 111.072(5)°, V = 1481.3(2) Å3 and Dx = 1.483 g.cm-3 respectively. The
structure of the compound has also been examined by using quantum chemical methods. The
molecular geometry and vibrational frequencies of monomeric and dimeric form of the title
compound in the ground state have been calculated by using the B3LYP/6-31G(d,p) level of
the theory. The calculated results show that the optimized geometry and the theoretical
vibration frequencies of the dimeric form are good agreement with experimental data. In
addition, HOMO – LUMO energy gap, molecular electrostatic potential map, thermodynamic
properties of the title compound were performed at B3LYP/6-31G (d,p) level of theory.
Key Words: Pyridazine and pyrazole core; Crystal structure; DFT, HOMO, LUMO
*Corresponding author. Tel: +900454 310 14 00
E-mail adress: canalasalvar@hotmail.com (C. Alaşalvar)
1

Introduction
The pyridazine and pyrazole pharmacophores were often used as versatile scaffolds
leading to a great variety of pharmacologically active compounds and certain derivatives
bearing these scaffolds demonstrated good anti-platelet properties [1-6]. Moreover, small
drug-like molecule libraries possessing vicinal diaryl template attracted great interest for
many medicinal chemists for developing novel drug candidates and our research on vicinal
diaryl systems produced a large number of compounds endowed with interesting
pharmacological properties against cyclooxygenase and lipoxygenase pathways [7-11].
Besides of the developing of novel drug synthesis, the development of computational
chemistry has contributed to the research of theoretical modeling of drug design, functional
material design, etc., in a positive way over the past decade. For instance, it has become
possible to guess the important physico-chemical properties of biological and chemical
systems by varied computational techniques [12]. Recently, density functional theory (DFT)
has been a milestone of theoretical modeling. Calculating many molecular properties with
comparable accuracies to traditional correlated ab-initio methods with more plausible
computational costs has become possible with the development of better and better exchange-
correlation functional. The studies in the literature showed that the DFT has a perfect
accuracy in reproducing the experimental values of in geometry, dipole moment, vibrational
frequency, etc. [13, 14].
Pyridazine and pyrazole heterocyclic cores have good anti-platelet properties. Levent
et all. synthesized and studied their against arachidonic acid (AA)-induced platelet
aggregation and identified 5-(4-Chlorophenyl)-1-(6-methoxypyridazin-3-yl)-1H-pyrazole-3-
carboxylic acid ( Scheme 1) as a starting compound for further derivatization for the
discovery of novel anti-platelet compounds [15]. But the crystal structure and theoretical
calculations of this compound has not been studied yet. In this paper, the title compound was
re-synthesized according to Ref. 15 and characterized by using FT-IR, single crystal X –ray
and DFT methods. Hydrogen bond geometry of the molecule was determined by using X-ray
difractometer. In addition, the properties of structural geometry, molecular electrostatic
potential map, frontier orbitals and thermodynamic properties for the title compound were
investigated at DFT/B3LYP/6-31G (d,p) level.
2

Scheme 1. Scaffold structure of the title compound
Experimental details
Synthesis
of
Methyl
5-(4-chlorophenyl)-1-(6-chloropyridazine-3-yl)-1H-pyrazole-3-
carboxylate (1)
To a mixture of methyl 4-(4-chlorophenyl)-2,4-dioxobutanoate (1 eq) and 6-chloro-3-
hydrazino-pyridazine (1 eq) in 25 ml methanol, conc. HCl (0.5 eq) was added. After stirring at
rt for 5 h, the precipitate was filtrated and recrystallized from methanol to yield 1 (75%). Mp
162-163oC; IR (ATR): 3129, 3084, 2977, 1726, 1094 cm-1; 1H-NMR (DMSO-d6): δ 3.87 (3H,
s), 7.25 (1H, s), 7.37 (2H, d, J=8.4 Hz), 7.43 (2H, d, J=8.4), 8.18 (1H, d, J=8.8 Hz), 8.23 (1H,
d, J=9.6 Hz); 13C-NMR (DMSO-d6): δ 52.86, 112.11, 127.68, 128.67, 129.22, 131.19,
132.58, 134.50, 145.21, 145.88, 155.72, 156.56, 162.12; HRMS (m/z): [M+H]+ calcd for
C15H11Cl2N4O2: 349.0259; found 349.0257 [15].
Synthesis of 5-(4-Chlorophenyl)-1-(6-methoxypyridazin-3-yl)-1H-pyrazole-3-carboxylic acid
(2)
Compound 1 (1 eq) was dissolved in 20 ml methanol containing sodium methoxide (3
eq) and refluxed for 2.5 hours. Water was added (30 ml) and the reaction mixture was heated
at reflux for another hour, diluted with water, and acidified. The precipitate formed was
washed with water and recrystallized from ethanol-water mixture to yield 2 (82%). Mp 225-
1
226oC; IR (ATR): 3381, 2976, 2600, 1694, 1089 cm-1; H-NMR (DMSO-d6): δ 4.04 (3H, s),
7.16 (1H, s), 7.34 (2H, d, J=8.8 Hz), 7.45 (2H, d, J=8.8), 7.52 (1H, d, J=9.2 Hz), 8.35 (1H, d,
13
J=9.6 Hz), 13.23 (1H, bs); C-NMR (DMSO-d6): δ 55.74, 111.31, 120.92, 128.44, 128.94,
129.25, 131.03, 134.19, 144.65, 146.30, 152.79, 163.33, 165.36; HRMS (m/z): [M+H]+ calcd
3

for C15H12ClN4O3: 331.0598; found 331.0602; Elemental Anal. Calcd for C15H11ClN4O3: C,
54.47; H; 3.35; N, 16.94; found C, 54.04; H, 3.31; N, 16.85.
As shown in Scheme 2, the 1,5-diarylpyrazole derivative (1) was synthesized by
condensation of methyl 4-(4-chlorophenyl)-2,4-dioxobutanoate with 3-chloro-6-
hydrazinylpyridazine in methanol in the presence of 0.5 eq HCl. Nucleophilic substitution of
6-chloro of pyridazine (1) with sodium methoxide followed by successive ester hydrolysis
yielded 6-methoxypyridazine analogue in acid form (2) [15].
Scheme 2. Synthetic pathway for compound 2 [15].
Materials and measurements
All chemicals and reagents used in this study were purchased from Sigma-Aldrich Chemical
Company (St Louis, MO, USA). IR spectrum was recorded on a Perkin-Elmer Spectrum one
FT-IR spectrometer in KBr pellets.
Crystal data for the title compound (2)
X-ray diffraction data were recorded on a STOE IPDS II single crystal diffractometer
(STOE & Cie GmbH, Darmstadt, Germany). The intensities collected were corrected for
Lorentz and polarization factors, absorption correction by integration method via X-RED32
software [16]. The structure was solved by direct methods using SHELXS-97 [17] and refined
with SHELXL-97 [17].
All non-hydrogen atoms were refined anisotropically. The refinement was carried out
using the full matrix least squares method on the positional and anisotropic temperature
parameters of non-hydrogen atoms corresponding to 425 crystallographic parameters. The
4

positions of the hydroxy H atoms were obtained from a difference map of the electron density
in the unit-cell and were refined freely. All other hydrogen atoms were refined using a riding
model with C–H = 0.93–0.96 Å. The constraint Uiso(H) = 1.2Ueq (CH) or 1.5Ueq(CH3) was
applied. Details of the data collection conditions and the parameters of the refinement process
are given in Table 1.
Computational details
We used Gauss – View molecular visualization program and Gaussian03 program
package for the all calculations [18, 19]. Starting geometries of compound were taken from
X-ray refinement data. The molecular structure of the compound in the ground state is
optimized by using B3LYP/6-31G(d,p) level of the theory. In DFT calculation, hybrid
functional are also used, the Becke’s three parameter functional (B3) [20] which defines the
exchange functional as the linear combination of Hartre- Fock, local and gradient – corrected
exchange terms. The B3 hybrid functional was used in combination with the correlation
functional of Lee, Yang and Parr [21]. For the compound, vibration frequencies were
calculated by using DFT/B3LYP with 6-31G (d,p) basis set. The Calculated frequencies were
scaled by 0.9627 [22]. Both geometries of the title compound and tetramethylsilane (TMS)
were fully optimized. 1H and 13C chemical shifts were computed. The standard
GIAO/B3LYP/6-31G(d) (Gauge-Independent Atomic Orbital) approach [23-24] applying
1
B3LYP level 6-31G(d,p) basic set was used for these calculations. The H and 13C NMR
chemical shifts are converted into the TMS scale by subtracting the calculated absolute
chemical shielding of TMS (  0  , where

is the chemical shift,  is the absolute
shielding and 0 is the absolute shielding of TMS), whose values is 31.76 ppm and 191,81
ppm for B3LYP/6-31G(d,p) level of the theory, respectively. In addition, MEP map, HOMO
– LUMO energy values and thermodynamic properties of the title compound were calculated
by using B3LYP/6-31G(d,p) level of the theory.
Results and discussions
Crystallographic study
The title compound (2) crystallizes in the triclinic space group P-1, an Olex-2 [25]
view of (2) is shown in Fig. 1 and Crystal data, data collection and refinement details for the
5

title compound were given in Table 1. The asymmetric unit in the crystal structure contains
two independed similar molecules. The title compound consists of a pyrazole-3-carboxylic
acid ring with 4-chlorophenyl and 6-methoxypyridazin substituents at the 1- and 5-positions,
respectively.
All bond distances in the pyrazole ring indicate partial double bond character, which
suggests a delocalized -electronic system throughout the ring [26]. Glancing at the Table 2,
the C3=C4 distance of 1.370(2) Å is slightly deviates from the average C=C double bond
length (average for C=C sp2=sp2 bond is 1.34 Å). The C2-C3 bond length of 1.395(2) Å is
slightly shorter than the pure C-C sp2-sp2 single bond (average length for such a bond is 1.48
Å) [27]. Moreover, the N=N bond length is shorter than those found in the above-cited
structures [N=N 1.373(2) Å 1.380(8) Å] [28].
For two molecules in the asymmetric unit, the dihedral angles between pyridazine and
phenyl rings, in an interesting way, is quite different. While the dihedral angle between (C5-
C10) and (C11-C12-C13-C14-N3-N4) mean planes is 48, 75º (10), the angle between (C5A-
C10A) and (C11A-C12A-C13A-C14A-N3A-N4A) mean planes is 84, 95º (12).
Hydrogen bond geometry values of the title compound are given Table 3. In the
packing of the title compound, two independed asymmetric units are connected by the O1-
H1…O2A and O1A-H1A…O2 hydrogen bonds into centro symmetric dimers resulting in
ring motifs, as depicted in Fig.2 [29].
Optimized geometry
The optimized parameters (bond lengths, bond angles, and dihedral angles) of
monomer and dimer forms of the title compound were obtained at B3LYP level with the 6-
31G (d,p) basis set and listed with experimental values in Table 2. The optimized molecular
structures of monomer and dimer forms of the title compound are shown in Fig. 3 (a) and (b),
respectively. Glancing at Table 2; C1 – O1, C1 – O2 bond lengths were calculated as 1.314,
1.236 Å and as 1.350, 1.215 Å for the dimeric form and monomeric form respectively. These
bond distances (C1 – O1 and C1 – O2) were observed as 1.285, 1.230 Å. Calculated bond
parameters for dimeric form are consistent with the experimental values, whereas the
calculated values for monomeric form deviates from experimental values especially on the
carboxylic acid group of the title molecule. The reason of these deviations, it can be
intramolecular hydrogen bond interactions in given Table 3.
6

Intramolecular interactions values in the title compound are calculated by using
B3LYP/6-31G (d,p) method and listed Table 4. Calculated and experimental hydrogen bond
interactions values are compatible with each other.
FT-IR and NMR spectra analyses
Vibrational frequencies of the title compound of monomer and dimeric form are
calculated by using DFT with 6-31G (d,p) basic set and some important vibration modes are
listed in Table 5, with their experimental values. FT – IR spectrum is shown in Fig. 4. The
carboxylic group (–COOH) of the title compound contains the C–O, C=O and O–H
vibrational modes. The very board peak observed between 2500–3300 cm–1 in IR spectrum
can be assigned to the O–H stretching vibration mode in the title molecule. But weak C–H
stretching bands occur in this region (near 3000 cm–1) and seen over of O–H band. O–H
stretching band was observed as 2990cm-1 in the Fig. 4. This band was calculated as 3619cm-1
and 2995cm-1 for monomer and dimer form of the title compound, respectively. The C=O
stretching band appears strongly in the region 1870–1540 cm–1 in which the position of C=O
stretching band depends on the physical state, electronic and mass effects of neighboring
substituents, conjugations and intramolecular and intermolecular hydrogen bonding [30–35].
C=O stretching band in the Fig. 4 was observed as 1697cm-1. This band was calculated as
1753cm-1 and 1694cm-1 for monomeric and dimeric form of the title compound, respectively.
Calculated values for O–H and C=O vibration of monomer form of title compound are bigger
than experimental values. This situation can be explained by the presence of O… H – O
strong intramolecular hydrogen bond given Table 3. As seen Table 5, calculated O–H and
C=O vibration values of dimeric form are in good agreement with experimental values.
The O – CH3 stretching vibration bands of methoxy group for the title compound is
observed at 1009cm-1, and this band for monomer and dimer form are found at 1004 and
1003cm-1 in our B3LYP/6-31G(d,p) calculations, respectively. The obtained results are in a
good agreement with literature [36-38].
The C – H, C – H3 and C – C vibration modes have been calculated at 3080 – 3172cm-
1 (C –H stretching), 2947 – 3052cm-1 (C – H3 stretching) and 1593cm-1 (C – C stretching) for
the dimeric form and 3081 – 3171cm-1, 2947 – 3053cm-1 and 1588cm-1 for monomeric form
and these bands are observed at 2955-3086, 2594-2880 and 1598cm-1 respectively.
The C – N + C – C stretching in the pyridazine ring for the monomeric and dimeric
form are computed at 1543cm-1 and 1546cm-1 respectively and this mode is observed at
7

1544cm-1. In the pyrazole ring, the C - N + C - C and C – N - C + C – N - N stretching modes
are calculated as 1430, 1399 cm-1 for monomeric form and 1432, 1411 cm-1 for dimeric form,
while these modes are observed as 1469 and 1409 cm-1 respectively.
1
Structural analysis of the compound was carried out with the help of H-NMR and
1
13
13C-NMR using DMSO-d6. Observed and calculated H-NMR and C-NMR chemical shift
1
values are given at Table 6. According to Table 6, theoretical and experimental values of H
13
and C NMR of the molecule are in good agreement except H atom the bounded to Oxygen
atom. Because of this, it can be O – H…O intramolecular interactions given in Table 3.
Molecular electrostatic potential analysis
The molecular electrostatic potential (MEP), V(r) at a given point r(x, y, z) in the
vicinity of a molecule, is defined in terms of the interaction energy between an electrical
charge which is generated from the molecule electrons and nuclei and a positive test charge(a
proton) located at r. For the system studied, the V(r) values are calculated by the equation
[39],

ZA
(r )


dr
V(r) 
  r  r

(RA  r)
A

(r )
where ZA is the charge of nucleus A located at RA,
is the electronic density function of

the molecule, and
is the dummy integration variable. To predict the reactive sites of
r
electrophilic and nucleophilic attack for the investigated molecule, the MEP at the B3LYP/6-
31G(d,p) optimized geometry of monomeric form was calculated and shown in Fig. 5. As
seen from Fig.5, the most negative regions are located on the O1 atom which can be
considered as possible site for electrophilic attack and its V(r) value is -0.042a.u. Other
negative region is located on the N1 atom and V(r) values are -0.040 a.u.. However, the
maximum positive region is located on the H atom bonded O2 atom and V(r) value is
0.052a.u. This indicates a possible site for nucleophilic attack. The MEP is related to the
electronic density and is a very useful descriptor for determining sites for electrophilic attack
and nucleophilic reactions as well as hydrogen-bonding interactions [40-43]. So, Fig.5
supports the existence of the intramolecular interactions given in Table 3.
8

HOMO - LUMO analysis
The most important orbitals in a molecule are the frontier molecular orbitals, called
HOMO and LUMO. HOMO implies that the outermost orbital filled by electrons, and
behaves as an electron donor while LUMO can be thought as the first empty innermost orbital
unfilled by electron and behaves as an electron acceptor. The energy of the HOMO is directly
related to the ionization potential and represents the ability of electron giving. But, LUMO
energy is directly related to the electron affinity and represents the ability of electron
accepting. The formed energy gap between HOMO and LUMO indicates the molecular
chemical stability [44]. The energy gap between HOMO and LUMO is a critical parameter to
determine molecular electrical transport properties. By using HOMO and LUMO energy
values for a molecule, chemical hardness–softness, electronegativity and electrophilicity
index can be calculated as follows:
I  A
2
    
(Electronegativity)
I  A
2
 
(Chemical hardness)
(Softness)
1
 
2
2
 
(Electrophilicity index)
2
Where
I A
and is ionization potential and electron affinity, and is I  EHOMO and
A  ELUMO , respectively [45-48]. Molecules which have a large HOMO–LUMO energy gap
are called ―hard‖ and which have a small HOMO–LUMO energy gap are called ―soft‖.
Frontier orbitals (HOMO – LUMO) of the title molecule were calculated by using B3LYP/6-
31G(d,p) method in gas phase. HOMO–LUMO energy gap, electronegativity, electrophilicity
index and chemical hardness and softness values of monomer and dimer form of title
molecule were listed in Table 7. The band gap energy of the one electron excitation from
HOMO to LUMO for monomer and dimer form is calculated about 4.68 eV and 4.59eV
respectively. This large HOMO–LUMO gap is an indication of a good stability and a high
chemical hardness for the title compound. For monomer and dimer form, 3D plots of highest
occupied molecular orbitals (HOMO), lowest unoccupied molecular orbitals (LUMO) were
shown in Fig. 6.
9

Thermodynamic Properties
All the thermodynamic calculations have been carried out in gas phase and they could
not be used in solution. Standard thermodynamic function: heat capacity (Cpo,m ), entropy (
o
Sm
o
) and enthalpy (
) based on vibrational analysis at the B3LYP/6-31G(d,p) level were
Hm
obtained and listed Table 8. The Table 8 indicates that standard heat capacity, entropies and
enthalpies increase at any temperatures from 200K to 500K, because the intensities of the
molecular vibration increase with increasing temperature. The correlation equations between
these thermodynamic parameters (Cp0,m
,
,
) and temperature T are as follows:
Sm0 Hm0
(R2=0.9981)
Cpo,m  1x104T2 0.2785T 1.9177
(R2=0.9989)
(R2=0.9998)
Smo  5x105T2 0.2863T 70.607
Hmo 1x104T2 0.0145T 0.5016
Conclusions
5-(4-Chlorophenyl)-1-(6-methoxypyridazin-3-yl)-1H-pyrazole-3-carboxylic acid has
been characterized by using FT-IR and X-ray technique experimentally and using B3LYP/6-
31G(d,p) method theoretically. Molecular geometry parameters and vibrational frequencies
values were calculated using B3LYP/6-31G(d,p) method for monomeric and dimeric form of
the compounds. Calculated values in the dimeric form were found to be more compatible with
experimental data. The MEP map shows that the negative potential sites are on
electronegative atoms as well as the positive potential sites are around the hydrogen atoms.
These sites give information about the region from where the compound can have
intermolecular and intramolecular interactions. For monomer and dimer form, HOMO-LUMO
energy gap of the molecule are 4.68eV and 4.59eV respectively. This large HOMO–LUMO
gap is an indication of a good stability and a high chemical hardness for the title compound.
C0
Sm0 Hm0
In addition, the correlations between the thermodynamic parameters (
temperatures T were also obtained.
,
,
) and
p,m
10

Supplementary material
Crystallographic data for the structures reported in this article have been deposited
with the Cambridge Crystallographic Data Centre as supplementary publication number
970299 (title compound). Copies of the data can be obtained free of charge on application to
CCDC 12 Union Road, Cambridge CB21 EZ, UK. Fax: +44 1223 336 033; e-mail:
data_request@ccdc.cam.ac.uk.
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13

Figure Captions
Fig. 1. Olex 2 plots of dimeric form of the title compound with atom numbering schemes.
Displacement ellipsoids are represented at 50% probability levels. H atoms are shown as
small spheres of arbitrary radius.
Fig. 2. Packing diagram of the title compound
Fig. 3. Theoretical structure of the title compound (a) Dimeric form (b)monomeric form
Fig. 4. FT-IR spectrum of the title compound
Fig. 5. Molecular Electrostatic Potential (MEP) Map of the title compound
Fig. 6. For title compound 3D plots of (a)HOMO; (b)LUMO
14

Fig. 1. Olex 2 plots of dimeric form of the title compound with atom numbering schemes.
Displacement ellipsoids are represented at 50% probability levels. H atoms are shown as
small spheres of arbitrary radius.
15

Fig. 2. Packing diagram of the title compound
16

Fig. 3. Theoretical structure of the title compound (a) Dimeric form (b)monomeric form
17

83.5
82
468
80
78
76
74
72
70
68
66
641
716
688
559
612
628
1562
676
1054
3416
540
1544
1507
2483
1364
928
548
1141
1100
1029
2734
2594
505
1171
734
1598
968
3086
3036
782
1090
2880
831
2990
2955
1195
1214
818
998
844
%T
64
62
60
58
56
54
52
50
1009
1444
1268
1251
1298
1697
1409
1469
47.8
4000.0
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
450.0
cm-1
Fig. 4. FT-IR spectrum of the title compound
18

Fig. 5. Molecular Electrostatic Potential (MEP) Map of the title compound (dimeric and
monomer form)
19

Fig. 6. For title compound 3D plots of (a) HOMO; (b) LUMO
20

Table 1
Crystal data, data collection and refinement detail for the title compound
Empirical formula
C30H22Cl2N8O6
Formula weight
661.46
Temperature/K
293(2)
Crystal system
triclinic
Space group
P-1
a/Å
9.612(1)
b/Å
9.894(1)
c/Å
17.380(1)
α/°
90.213(5)
β/°
104.987(5)
γ/°
111.072(5)
1481.3(2)
Volume/Å3
Z
2
ρcalc mg/mm3
/mm-1
1.483
0.279
F(000)
680.0
Crystal size/mm3
2range for data collection
Index ranges
Reflections collected
Independent reflections
0.28 × 0.21 × 0.18
4.44 to 53.66°
-12 ≤ h ≤ 12, -12 ≤ k ≤ 12, -21 ≤ l ≤ 21
21520
6297[R(int) = 0.0498]
Data/restraints/parameters 6297/0/425
Goodness-of-fit on F2
0.879
Final R indexes [I>=2σ (I)] R1 = 0.0492, wR2 = 0.1017
Final R indexes [all data] R1 = 0.1313, wR2 = 0.1240
Largest diff. peak/hole / e Å-3 0.28/-0.29
21

Table 2
Selected molecular structure parameters
Parameters
Experimental
B3LYP/6-31G(d,p)
Monomer
Dimer
Bond lengths (Å)
C1—O2
1.230 (3)
1.285 (3)
1.230 (3)
1.287 (3)
1.469 (3)
1.361 (2)
1.323 (3)
1.374 (3)
1.358 (3)
1.746 (3)
1.744 (3)
1.215
1.350
-
1.236
1.314
1.236
1.314
1.476
1.351
1.332
1.391
1.339
1.758
1.757
C1—O1
C1A—O2A
C1A—O1A
C1—C2
-
1.476
1.352
1.332
N1—N2
N1—C2
N2—C4
N3—N4
1.339
1.758
-
Cl1—C8
Cl1A—C8A
Bond angles (
C2—C1—O1
C2—C1—O2
N2—C4—C5

)
116.3 (2)
119.5 (2)
127.2 (2)
130.81 (19)
122.7 (3)
124.0 (2)
116.81 (19)
118.5 (2)
113.56
123.29
128.08
130.9
115.14
119.99
128.21
130.98
123.55
124.86
116.36
117.63
C4—N2—C11
C4—C5—C10
O2—C1—O1
N1—N2—C11
C4—C5—C6
123.63
123.13
116.41
117.68
Dihedral angles (  )
C3—C2—C1—O1
C3—C2—C1—O2
N1—C2—C1—O2
N1—C2—C1—O1
178.0 (3)
-2.6 (5)
179.83
0.013
-178.93
0.89
174.7 (3)
-4.8 (5)
179.84
-0.335
-178.85
1.32
22

Table 3
Experimental hydrogen-bond geometry values (Å, °)
D—H…A
D–H (Å)
H···A (Å)
1.78(4)
D···A (Å) D–H···A °
O1A—H1A…O2 0.87(4)
2.656 (3)
2.661 (3)
179(4)
173(4)
O1—H1…O2A
0.91(5)
1.76(5)
Table 4
Hydrogen-bond geometry values on B3LYP/6-31G(d,p) (Å, °)
D—H…A
O1A—H1A…O2 1.007
O1—H1…O2A
D–H (Å)
H···A (Å)
1.627
1.627
D···A (Å) D–H···A °
2.635
2.634
179.11
179.12
1.007
Table 5
Some experimental and calculated vibrational frequencies (cm-1) and assignments of the
compounds on B3LYP/6-31G(d,p).
Experimental (cm-1) B3LYP/6-31G(d,p)
Assignments
Monomer (cm-1) Dimer (cm-1)
v
OH
CH
CH3
CO
2990
3619
2995
v
v
v
v
v
v
2955 - 3086
2594 - 2880
1697
1598
1544
3081 - 3171
2947 - 3053
1753
3080 - 3172
2947 - 3052
1694
CC Benzene ring
1588
1593
v
CN+ CC Pyridazine ring
1543
1546
v
CN+ CC Pyrazole ring
1469
1430
1432
v
v
C-N-C + C-N-N pyrazole
1409
1009
1399
1004
1411
1003
ring
v(O CH3)
23

Table 6
Experimental and theoretical 1H and 13C isotropic chemical shifts (with respect to TMS,
all values in ppm) for the title compound
Atom
H2
B3LYP/6-31G(d,p) (ppm)
4.16
Experimental (ppm)
4.04
H5
3.89
4.04
H6
4.25
4.04
H4
6.83
7.52
H1
7.85
8.35
H7
5.77
13.23
H3
7.16
7.16
H28
H30
H32
H34
C26
C19
C17
C21
C16
C33
C29
C27
C31
C25
C23
C20
C18
C15
C24
7.24
7.24
8.81
7.4
7.34
7.45
7.34
7.45
53.98
55.74
112.42
121.54
112.29
124.47
122.46
122.31
127.17
131.56
140.16
144.42
140.01
150.17
158.53
154.73
111.31
120.92
128.44
128.94
129.25
129.25
131.03
131.03
134.19
144.65
146.30
152.79
163.33
165.36
24

Table 7
The calculated HOMO, LUMO energy values, HOMO – LUMO energy gap, electrophilicity
index, electronegativity, chemical hardness and softness of the title compound
Parameters
HOMO (eV)
LUMO (eV)
Monomer form
-6.45
Dimer form
-6.34
-1.77
-1.75
4.68
4.59
E (energy gap (eV)
4.11
2.34
0.21
4.04
2.30
0.22

(eV)
(eV)


(eV)
(eV)

3.61
3.55
Table 8
Thermodynamic properties at different temperatures at B3LYP/6–31G(d,p) level
Hmo
Smo
Cpo,m
T
(cal mol-1K-1)
(Kelvin)
(cal mol-1K-1)
(kcal/mol)
200
250
298.15
300
350
400
450
500
6.63
9.69
53.56
64.78
73.01
75.85
86.40
96.15
126.17
139.77
149.85
152.92
165.72
178.17
190.25
201.94
12.79
13.30
17.45
22.12
27.24
32.79
104.99
112.88
25

Highlights
 The title compound are re-synthesized and characterized experimentally and
theoretically.
 Both monomer and dimeric form of The title compound are optimized by using
B3LYP/6-31G(d,p)
 Observed and calculated values were compared.
 HOMO – LUMO, MEP map and Thermodynamic properties of the title compound are
predicted.