Analysis of Intermolecular Interactions in 2,3,5 Trisubstituted Pyrazoles Derivatives: Insights into Crystal Structures, Gaussian B3LYP/6-311G (d,p), PIXELC and Hirshfeld Surface

Article abstract of DOI:10.1007/s10870-016-0667-6

Abstract: Two derivatives of pyrazole have been synthesized with one of the systematic substitutions made on the ortho position of the phenyl ring attached to the pyrazole moiety and characterised via single crystal X-ray diffraction. The nature of the molecules appear as planar with the hydrogen bonding features analysed quantitatively. The derivatives are geometrically optimized and studied for its molecular confirmation at the B3LYP/6-311G (d,p). The structure overlay, molecular packing and intermolecular hydrogen bonding are studied quantitatively using Hirshfeld surface and 2D fingerprint plots. In both?the compounds, packing of?the molecules is derived via strong O–H···N and weak C–H···O, C–H···π interactions stabilizing the packing. Further, the structure overlay between the experimental structures and the geometrically optimized structures along with frequency analysis at the quantum chemical level shows the deviation in the central pyrazole moiety and the substituted phenyl ring with the RMSD value of 0.5051 and 0.6305?? respectively. The lattice energy?is calculated for both the compounds using PIXELC module in Coulomb–London–Pauli (CLP) package and is partitioned into corresponding coulombic, polarization, dispersion and repulsion contributions. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s10870-016-0667-6

J Chem Crystallogr
DOI 10.1007/s10870-016-0667-6
ORIGINAL PAPER
Analysis of Intermolecular Interactions in 2,3,5 Trisubstituted
Pyrazoles Derivatives: Insights into Crystal Structures, Gaussian
B3LYP/6-311G (d,p), PIXELC and Hirshfeld Surface
Gayathri Purushothaman1 Vijay Thiruvenkatam1
•
Received: 4 April 2016 / Accepted: 3 September 2016
Ó Springer Science+Business Media New York 2016
Abstract Two derivatives of pyrazole have been synthe-
sized with one of the systematic substitutions made on the
ortho position of the phenyl ring attached to the pyrazole
moiety and characterised via single crystal X-ray diffrac-
tion. The nature of the molecules appear as planar with the
hydrogen bonding features analysed quantitatively. The
derivatives are geometrically optimized and studied for its
molecular confirmation at the B3LYP/6-311G (d,p). The
structure overlay, molecular packing and intermolecular
hydrogen bonding are studied quantitatively using Hirsh-
feld surface and 2D fingerprint plots. In both the com-
pounds, packing of the molecules is derived via strong O–
HÁÁÁN and weak C–HÁÁÁO, C–HÁÁÁp interactions stabilizing
the packing. Further, the structure overlay between the
experimental structures and the geometrically optimized
structures along with frequency analysis at the quantum
chemical level shows the deviation in the central pyrazole
moiety and the substituted phenyl ring with the RMSD
˚
value of 0.5051 and 0.6305 A respectively. The lattice
energy is calculated for both the compounds using PIX-
ELC module in Coulomb–London–Pauli (CLP) package
and is partitioned into corresponding coulombic, polariza-
tion, dispersion and repulsion contributions.
This paper is dedicated to Professor K. Venkatesan.
Electronic supplementary material The online version of this
article (doi:10.1007/s10870-016-0667-6) contains supplementary
material, which is available to authorized users.
& Vijay Thiruvenkatam
vijay@iitgn.ac.in
1
Biological Engineering and Physics, Indian Institute of
Technology Gandhinagar, Gandhinagar, Gujarat 382355,
India
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J Chem Crystallogr
Graphical Abstract
Keywords Molecular confirmation Á B3LYP/6-311G
(d,p) Á PIXELC Á Hirshfeld surface Á 2D fingerprint Á Lattice
energy
different properties like de, dnorm, shape index and
curvedness helps in visualizing the intermolecular inter-
actions and the crystal packing behaviour of molecules in
the three dimensional space [21]. The 2D-fingerprint plot
provides the decomposition of Hirshfeld surfaces into dif-
ferent intermolecular interactions present in crystal struc-
ture [22] and this analysis is done by CrystalExplorer3.1
program [23, 24]. PIXELC calculations are performed to
determine intermolecular interaction energies and lattice
energy. It permits the analysis of lattice and intermolecular
interaction energies between pairs of molecules in terms of
coulombic, polarisation, dispersion and repulsion contri-
butions for the overall energy [25].
Introduction
Pyrazoles are an important class of heterocyclic com-
pounds with the five membered ring consisting of two
nitrogen atoms known to possess widespread potential
biological activities such as antibacterial [1, 2], anti-in-
flammatory [3], antifungal [4], analgesic [5], antitumor [6],
antidepressant [7], antiprotozoal [8] and herbicidal [9].
Pyrazoles are good inhibitors of monoamine oxidase
(MAO) which causes several psychiatric and neurological
diseases [10]. These enormous pharmacological actions of
pyrazole formulate them as valuable active ingredients of
medicine and plant protecting agents [11]. To make them
as a better drug it is important to know how to design the
molecule based on the specific target [12]. By knowing the
chemical structure and by studying the 3D structures, we
can understand the nature of intermolecular interactions in
these pyrazole derivatives.
Here, we report the experimental structure by single
crystal XRD and optimized structure by density functional
theory (DFT) [26] of 2,3,5 trisubstituted pyrazoles:(3-(4-
hydroxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-
yl)(pyridin-3-yl)methanone (II) (I) and (3-(4-hydrox-
yphenyl)-5-o-tolyl-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-
3-yl)methanone (II) (II) and the quantitative analysis of
intermolecular interactions to study the molecular packing
and supramolecular assembly via interaction energy
calculations.
Intermolecular hydrogen bonding are the key players to
form supramolecular assembly in crystals that are well
studied in the literature [13–17]. The presence of five
membered ring and the pyridinyl ring drive the molecules
to form highly directional intermolecular interactions like
strong N–HÁÁÁO and the weak C–HÁÁÁO interactions, hence
the supramolecular assembly [18].
Experimental Section
Synthesis and Crystallization of the Title
Compounds
Hirshfeld surface analysis is an extremely useful tech-
nique to understand the packing, nature of intermolecular
interactions and the molecular boundaries of a given
molecule [19, 20]. The Hirshfeld surface mapped with
The pyrazole derivatives were synthesized according to the
method given in [27], which includes the well-known
Claisen–Schmidt scheme for synthesis of chalcones, fol-
lowed by refluxing of the chalcones with nicotinic acid
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J Chem Crystallogr
Fig. 1 Schematic diagram and the molecular geometry with the atom numbering of I (a, c) and II (b, d), displacement ellipsoids are drawn at the
50 % probability level
hydrazide using methanol to get the final products (Fig. 1).
The crystals of I and II suitable for X-ray diffraction
analysis is grown by slow evaporation method using
methanol and morphologically they are block and plate
shaped respectively.
respectively. Details of the data collection and refinement
are given in Table 1.
Analysis of Intermolecular Interaction by Hirshfeld
Surface and Fingerprint Plot
Data Collection
A detailed study of intermolecular interactions in I and II
via Hirshfeld surface calculation and fingerprint plot is
been done using CrystalExplorer3.1 [23] by submitting the
crystallographic information files (cif) of I and II. The
Hirshfeld surface mapped with dnorm, shape index,
curvedness states about the distribution of electron densi-
ties relate to the intermolecular interactions and the crystal
packing properties of molecules in the three dimensional
space [19]. The overall intermolecular interactions con-
tributed by each of these interactions (C–H, O–H, N–H and
H–H) are estimated using the 2D fingerplot [22]. To
visualize the electrostatic complementarities in the crystal
packing, electrostatic potential are mapped on the Hirsh-
feld surface [35] and it is done by using STO-3G basis set
The single crystal data were collected on a Bruker AXS
smart Apex CCD diffractometer using graphite
˚
monochromated MoKa (k = 0.7107 A) radiation at
150 K. The collected data were reduced using SAINT-
PLUS software and an empirical absorption correction is
applied using the package SADABS [28] available in the
Bruker software package. The crystal structure is solved by
direct methods using SHELXS97 [29] and refined by full
matrix least square methods using SHELXL97 present in
the program suite WinGX (Version 2014) [30, 31]. The
software ORTEP-3 [32], PLATON [33], CAMERON [34]
and Mercury [28] are used in generating the molecular
diagram, geometrical calculations and packing diagram
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J Chem Crystallogr
Table 1 Crystallographic
information of I and II
Crystal data
I
II
Crystal size (mm)
Solvent
0.5 9 0.45 9 0.4
MeOH
0.55 9 0.50 9 0.45
MeOH
Formula
C21H17N3O2
343.38
C22H19N3O2
357.40
Formula weight (g mol-1
Temperature (K)
Radiation
)
290 (2)
290 (2)
MoKa
MoKa
˚
Wavelength (A)
0.71073
Monoclinic
P21/c
0.71073
Crystal system
Space group
Monoclinic
P21/c
˚
a (A)
14.733 (5)
11.125 (4)
10.993 (4)
90
11.735 (5)
12.027 (5)
13.102 (6)
90
˚
b (A)
˚
c (A)
a (°)
b (°)
c (°)
109.208 (5)
90
105.666 (7)
90
3
˚
Volume (A )
1701.4 (10)
4
1780.4 (13)
4
Z
Density (g cm-3
)
1.340
1.333
l (mm-1
F (000)
hmin,max
)
0.088
0.087
720
752
2.3, 25.5
(-17,17), (-13,13), (-13,13)
Fixed
2.3, 25.5
(-14,14), (-14,14), (-15,15)
Fixed
hmin,max, kmin,max, lmin,max
Treatment of hydrogens*
No. of reflns measured
No. of unique reflns
No. of parameters
R_all, R_obs
11,704
12,695
3148
3311
236
246
0.080, 0.054
0.141, 0.131
-0.205, 0.195
1.050
0.059, 0.042
0.116, 0.109
-0.143, 0.142
1.075
wR2_all, wR2_obs
-3
Dqmin, max (eA
˚
)
GooF
and the crystal geometry is used as the input in the TONTO
[36] integrated with CrystalExplorer3.1.
correlation function (LYP) with the basis set of 6-311G
(d,p) [37]. Geometry optimizations has been done in gas
phase at DFT level of theory using B3LYP without any
symmetry restrictions and all the optimized geometries
confirmed by frequency analysis at the same level of theory
as explained by Tokay et al. [38]. Geometry optimization
and frequency calculations carried out using Gaussian 09
package by submitting the cif files of I and II [39]. Overlay
and RMSD calculation of experimental and calculated
structures of I and II are done by Chemcraft [40].
Geometry Optimization and Frequency Analysis
of I and II
To get the optimized structure of I and II, quantum-
chemical calculations were performed using Becke’s three
parameter exchange function (B3) with Lee–Yang–Parr
˚
Table 2 Displacement D (A) of atom C1 from the least-squares plane formed by atoms C2/C3/N1/N2 for I and II. The group of atoms deviates
˚
significantly from planarity and puckering parameters (A) for the five-membered pyrazole ring of I and II
˚
Displacement D (A)
˚
Puckering parameters: Q2 (A)
Compound
Puckering parameters: u2 (°)
I
0.090 (2)
0.143 (2)
78.2 (8)
80.7 (6)
II
0.0963 (18)
0.1543 (18)
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J Chem Crystallogr
Table 3 Dihedral angle (°) between the least-squares planes for I and
II. 1 is the least squares plane through atoms C1–C3/N1/N2, 2 is the
least-squares plane through atoms C5–C10, 3 is the least-squares
plane through atoms C11–C16 and 4 is the least-squares plane
through atoms C17–C21/N3
Compound
1/2
1/3
1/4
2/3
2/4
3/4
I
77.5 (1)
78.5 (1)
1.3 (1)
32.8 (1)
15.1 (1)
76.3 (1)
80.4 (1)
82.6 (1)
75.0
32.4 (1)
28.4 (1)
II
13.4 (1)
Fig. 2 A partial packing diagram for I, a depicting the formation of
O–HÁÁÁN and C–HÁÁÁO interactions (dotted lines) along a-axis (b).
Depicting the formation of C–HÁÁÁp interactions (dotted lines) along
c-axis, Cg1 and Cg2 are the centroids of rings phenyl and
hydroxyphenyl, respectively. Molecules labelled with asterisk suf-
fixes are at the symmetry positions (1-x, y, -z) and (-x, 1 ? y, -z),
respectively
the experimentally obtained geometry file. The total energy
as well as intermolecular interaction energy of the selected
molecular pairs are portioned into coulombic, polarization,
dispersion and repulsion by the software package [43]. The
molecular pairs were chosen by the symmetry codes cal-
culated from PIXELC resultant file by using matrix cal-
culation and mercury.
Result and Discussion
Database Survey
Cambridge Structure Database (Version 5.36, update Feb
2015) [44–46] search for I and II was carried out. The
substructure search for both I and II yielded zero hits. The
similarity search with the cut off 0.5 for I yielded 129 hits,
with the maximum similarity coefficient of 0.891(CSD
code: MENRAZ, (3-(2-Hydroxyphenyl)-5-phenyl-4,5-di-
hydropyrazol-1-yl)(pyridin-3-yl)methanone) and for II
there are 103 hits with the maximum similarity coefficient
of 0.833 (CSD code: MENRAZ).
Fig. 3 A partial packing diagram for II, depicting the formation of
O–HÁÁÁN and C–HÁÁÁO interactions (dotted lines) along b-axis
Lattice Energy Calculation for I and II
The total lattice energy of I and II were calculated using
PIXELC module in Couloumb–London–Pauli (CLP)
package (Version 3.0, Nov 2015) [41, 42] by submitting
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J Chem Crystallogr
Symmetric codes
Table 4 Intermolecular and
intramolecular hydrogen bonds
for I
˚
D–H (A)
˚
˚
Donor-HÁÁÁacceptor
HÁÁÁA (A)
DÁÁÁA (A)
–DHÁÁÁA (°)
O(2)–H(2)ÁÁÁN(3)
C(19)–H(19)ÁÁÁO(1)
C(18)–H(18)ÁÁÁN(1)
0.82
0.93
0.93
1.96
2.52
2.37
2.756 (3)
3.314 (3)
2.825 (3)
163
144
110
-x, -1/2 ? y, 1/2 - z
x, 3/2 - y, 1/2 ? z
–
Table 5 Intermolecular and
intramolecular hydrogen bonds
for II
˚
D–H (A)
˚
˚
Donor-HÁÁÁacceptor
HÁÁÁA (A)
DÁÁÁA (A)
–DHÁÁÁA (°)
Symmetric codes
O(2)–H(2)ÁÁÁN(3)
C(7)–H(7)ÁÁÁO(1)
C(18)–H(18)ÁÁÁN(1)
0.82
0.93
0.93
1.97
2.55
2.31
2.780 (2)
3.402 (3)
2.926 (2)
170
153
123
-x, -1/2 ? y, 1/2 - z
1 - x, -y, -z
–
Fig. 4 Hirshfeld surfaces of
I mapped with a dnorm
b curvedness and c shape-index
,
Fig. 5 Hirshfeld surfaces of II
mapped with a dnorm
b curvedness and c shape-index
,
Fig. 6 Contribution of different kinds of intermolecular interaction
for the overall intermolecular interactions in I: A Hirshfeld surface
representations with the function dnorm plotted onto the surface
a HÁÁÁH, b CÁÁÁH, c OÁÁÁH, d NÁÁÁH, e CÁÁÁN and f CÁÁÁC; B 2D
h CÁÁÁH, i OÁÁÁH, j NÁÁÁH, k CÁÁÁN and l CÁÁÁC. The outline of the full
fingerprint is shown in gray. di is the closest internal distance from a
given point on the Hirshfeld surface and de is the closest external
contacts
˚
fingerprint of I with di and de ranging from 1.0 to 2.8 A: g HÁÁÁH,
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J Chem Crystallogr
Fig. 7 Contribution of different kinds of intermolecular interaction
for the overall intermolecular interactions in II by Hirshfeld surface
representations with the function dnorm plotted onto the surface and
d CÁÁÁH; e, f OÁÁÁH; g, h NÁÁÁH; i, j CÁÁÁC; k, l NÁÁÁC and m, n OÁÁÁC.
The outline of the full fingerprint is shown in gray. di is the closest
internal distance from a given point on the Hirshfeld surface and de is
the closest external contacts
˚
2D fingerprint with di and de ranging from 1.0 to 2.8 A a, b HÁÁÁH; c,
Fig. 8 Percentage contributions to the Hirshfeld surface area for the various intermolecular contacts interactions in I (a) and II (b)
Crystal Data
(crystallographic numbering) forming the flap; deviations
from the least square planes are given in Table 2. The
remaining atoms of the ring (N1, N2, C2, C3) are coplanar,
with the out-of-plane distances being -0.0666 (19) and
The two compounds crystallize in monoclinic crystal sys-
tem with the space group P21/c, each having one molecule
present in the asymmetric unit (Table 1). Figure 1 shows
the molecular structure along with the atom numbering
scheme. The two structures with central pyrazole ring have
bond angles and bond lengths within the normal ranges
[47]. In both I and II the central pyrazole ring is in the
envelope conformation, with chiral atom C1
˚
-0.0693 (15) A for atom N2, in I and II respectively. The
dihedral angles between the central pyrazole ring and the
remaining six membered rings via pyridine ring, hydroxyl
phenyl ring, phenyl ring and the methyl substituted phenyl
ring in II are 77.5° (1), 1.3° (1), 32.8° (1) and 78.5° (1),
13.4° (1), 15.1° (1) respectively (Table 3). In both the
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J Chem Crystallogr
Fig. 9 Important intermolecular interactions and crystal packing in I (a) and II (b)
Fig. 10 Electrostatic potentials
mapped on Hirshfeld surfaces
for molecules in I (a) and II (b)
Fig. 11 The overlapped
structure of experimental by
single crystal XRD (Black) and
the optimized structure (yellow)
by Gaussian 09 with the basic
set of B3LYP/6-311G (d,p)
using Chemcraft for I (a) and II
(b) (Color figure online)
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J Chem Crystallogr
Table 6 Comparison of
experimental and calculated
˚
Distance (A)
˚
Distance (A)
Atoms
Atoms
˚
bond lengths (A) of I
SCXRD
B3LYP/6-311G (d,p)
SCXRD
B3LYP/6-311G (d,p)
C1–C2
1.527 (3)
1.513 (3)
0.9800
1.550
1.519
1.090
1.518
1.095
1.091
1.462
1.502
1.398
1.395
1.392
1.085
1.394
1.084
1.392
1.084
1.393
1.084
1.085
1.409
1.401
1.382
1.083
C13–C14
C13–H13
C14–C15
C15–C16
C15–H15
C16–H16
C17–C18
C17–C21
C18–H18
C19–C20
C19–H19
C20–C21
C20–H20
C21–H21
N1–C3
1.395 (3)
0.9300
1.401
1.083
1.395
1.391
1.086
1.083
1.395
1.399
1.081
1.393
1.087
1.387
1.084
1.083
1.231
1.376
1.486
1.376
1.33
C1–C5
C1–H1
1.375 (3)
1.384 (3)
0.9300
C2–C3
1.500 (3)
0.9700
C2–H2A
C2–H2B
C3–C11
C4–C17
C5–C6
0.9700
0.9300
1.464 (3)
1.497 (3)
1.378 (3)
1.387 (3)
1.381 (3)
0.9300
1.388 (3)
1.381 (3)
0.9300
C5–C10
C6–C7
1.372 (3)
0.9300
C6–H6
1.381 (3)
0.9300
C7–C8
1.373 (4)
0.9300
C7–H7
0.9300
C8–C9
1.357 (4)
0.9300
1.287 (3)
1.392 (3)
1.485 (3)
1.357 (3)
1.329 (3)
1.339 (3)
1.225 (3)
1.356 (3)
0.8200
C8–H8
N1–N2
C9–C10
C9–H9
1.377 (3)
0.9300
N2–C1
N2–C4
C10–H10
C11–C12
C11–C16
C12–C13
C12–H12
0.9300
N3–C18
N3–C19
O1–C4
1.395 (3)
1.393 (3)
1.378 (3)
0.9300
1.335
1.224
1.362
0.963
O2–C14
O2–H2
compounds, there is intramolecular C–HÁÁÁN hydrogen
bond between the pyridine CH and the pyrazole N1 atom,
thus creating the coplanar conformation, where,
Waals radii and the red and blue colour indicate the dis-
tances shorter and longer than the van der Walls radii
respectively [49]. The dark red spots in Fig. 4a show the
O–HÁÁÁN and C–HÁÁÁO interactions and the light spots
indicate the H–H contacts. In Figs. 4b and 5b the curved-
ness surface highlights that the HS is intensely flat (green)
and with some curved regions (blue) which results in the
stacking of the molecule in the crystal [50]. The shape
index on the HS is the basic tool to visualize the p–p
stacking by the presence of adjacent red and blue triangles
and Figs. 4c and 5c explain that there is no significant p–p
stacking interactions in both the compounds by the absence
of adjacent red and blue triangles in the shape index surface
[51]. But crystal structure of I shows that there is a
presence of C–HÁÁÁp interaction in C2–H2AÁÁÁcg2 and C20–
H20ÁÁÁcg1 as shown in the Fig. 2b. At the same time
presence of wings in the fingerprint image (Fig. 5b and h)
shows the presence of C–H contacts which may help in the
CÁÁÁH–p interactions via C2–H2AÁÁÁcg2 and C20–
H20ÁÁÁcg1.
˚
˚
H18ÁÁÁN1 = 2.37 A, C18ÁÁÁN1 = 2.825 (3) A and C18–
˚
H18ÁÁÁN1 = 110°
in
I;
H18ÁÁÁN1 = 2.31 A,
˚
C18ÁÁÁN1 = 2.926 (2) A and C18–H18ÁÁÁN1 = 123° in II
(Figs. 2, 3). Strong inter and intra molecular hydrogen
bonding features can be seen in the pyrazole substituted
ring systems, as shown in Table 4 for I and Table 5 for II.
A ring puckering analysis [48] of the five-membered
pyrazole ring gives the parameters listed in Table 2.
Hirshfeld Surface Analysis
In order to the study the intermolecular interactions in I and
II, the Hirshfeld surface (HS) analysis and related 2D
finger plots are calculated using CrystalExplorer 3.1. The
intermolecular interactions in I and II are visualized by
mapping the HS with the different properties like de, dnorm
,
shape index and curvedness (Figs. 4, 5). In the HS with the
dnorm (Figs. 4a, 5a) white colour surface indicate the con-
tacts with the distances equal to the sum of the van der
All the intermolecular interactions are highlighted in
dnorm molecular Hirshfeld surfaces and the 2D fingerprint
plot for I and II are shown in the Figs. 6, 7 and 8. It
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J Chem Crystallogr
B3LYP/6-311G (d,p)
Table 7 Comparison of
experimental and calculated
˚
bond lengths (A) of II
˚
Distance (A)
˚
Distance (A)
Atoms
Atoms
SCXRD
B3LYP/6-311G (d,p)
SCXRD
O1–C4
1.225 (2)
1.360 (2)
0.8200
1.226
1.362
0.963
1.289
1.375
1.492
1.373
1.336
1.335
1.522
1.549
1.518
1.462
1.501
1.407
1.399
1.511
1.400
1.391
1.392
1.390
1.401
1.409
1.382
1.401
C14–C15
C15–C16
C17–C18
C17–C21
C19–C20
C20–C21
C1–H1
1.374 (3)
1.383 (3)
1.387 (2)
1.387 (3)
1.371 (3)
1.374 (3)
0.9800
0.9700
0.9700
0.9300
0.9300
0.9300
0.9300
0.9300
0.9300
0.9300
0.9300
0.9300
0.9300
0.9300
0.9300
0.9600
0.9600
0.9600
1.395
1.391
1.401
1.399
1.393
1.387
0.98
O2–C14
O2–H2
N1–C3
1.292 (2)
1.401 (2)
1.480 (2)
1.356 (2)
1.342 (2)
1.332 (3)
1.512 (2)
1.540 (3)
1.504 (3)
1.466 (2)
1.502 (2)
1.402 (2)
1.380 (2)
1.495 (3)
1.394 (3)
1.376 (3)
1.364 (3)
1.384 (3)
1.387 (3)
1.385 (3)
1.381 (3)
1.392 (3)
N1–N2
N2–C1
N2–C4
N3–C18
N3–C19
C1–C5
C2–H2A
C2–H2B
C7–H7
1.086
1.091
1.095
1.084
1.084
1.084
1.085
1.083
1.083
1.086
1.084
1.081
1.087
1.084
1.083
1.091
1.093
C1–C2
C8–H8
C2–C3
C9–H9
C3–C11
C4–C17
C5–C6
C10–H10
C12–H12
C13–H13
C15–H15
C16–H16
C18–H18
C19–H19
C20–H20
C21–H21
C22–H22A
C22–H22B
C22–H22C
C5–C10
C6–C22
C6–C7
C7–C8
C8–C9
C9–C10
C11–C16
C11–C12
C12–C13
C13–C14
clearly indicates that, in I the overall intermolecular
interactions contributed by O–H, N–H, C–H, C–C, C–N
and H–H, the maximum contribution are given by H–H
(41.5 %) and C–H (32.4 %) followed by O–H (13.7 %),
N–H (8.2 %), N–C (2.5 %) and C–C(1.8 %). Similarly for
II, the overall intermolecular interactions are contributed
in the order: H–H (48.5 %) [ C–H (26.1 %) [ O–H
present in the molecule which act as hydrogen acceptors
and the positive potentials are concentrated in the region
around the hydrogen atoms.
Comparison of Molecular Confirmation
of Experimental Single Crystal XRD Structure
and Optimized Structure of the Title Compounds
(11.5 %) [ N–H
(7.3 %) [ C–C
(2.7 %) [ O–C
(2.1 %) [ N–C (2.0 %). The higher amount of H–H
interaction in both the compounds shows that van der
Waals interaction also plays a major role in the crystal
packing [50]. Some of the important intermolecular
interactions in I and II are visualized in Fig. 9. The
electrostatic complementation of the I and II are shown in
Fig. 10. The blue region indicates the positive electro-
static potential (hydrogen donor) whereas the red region
indicates the negative electrostatic potential [35]. The
electrostatic map of the both compounds shows that the
negative potential (red colour) are concentrated in the
region of electronegative oxygen and nitrogen atoms
Geometry optimization and frequency analysis are done
using Gaussian 09 with B3LYP function and a basis set of
6-311G (d,p) to get the optimized structure of I and II. The
resultant optimized structures are compared with the
experimental single crystal XRD structure by comparing
the structural parameters. The structural superimposition of
experimental and calculated structures of I and II are
shown in Fig. 11. The overall RMSD including hydrogen
atoms for the experimental and the optimized structures for
˚
I and II are 0.5051 and 0.6305 A respectively. In both the
compounds, the benzene ring attached to the C1 of the
pyrazole ring in the optimized structure are more deviated
123

J Chem Crystallogr
Table 8 Comparison of experimental and calculated bond angles (°) of I
Atoms
Angle (°)
Atoms
Angle (°)
SCXRD
B3LYP/6-311G (d,p)
SCXRD
B3LYP/6-311G (d,p)
C14–O2–H2
N2–N1–C3
109
109.4742
107.8862
112.6461
124.4353
122.8414
117.2463
100.5619
114.6112
112.0837
103.1121
120.6464
125.6451
113.6508
121.2307
118.6642
120.0988
119.7013
118.5203
121.7595
120.322
N3–C18–C17
N3–C19–C20
C19–C20–C21
C17–C21–C20
N2–C1–H1
124.2 (2)
122.83 (19)
119.1 (2)
119.2 (2)
110
124.1892
122.1892
122.828
107.89 (16)
112.65 (16)
124.43 (17)
122.84 (16)
117.25 (19)
100.56 (16)
114.61 (16)
112.09(16)
103.11 (17)
120.65 (17)
125.65 (18)
113.65 (19)
121.2 (2)
N1–N2–C1
C1–N2–C4
119.1187
119.2163
109.7464
109.7431
109.744
N1–N2–C4
C18–N3–C19
N2–C1–C2
C2–C1–H1
110
C5–C1–H1
110
C2–C1–C5
C1–C2–H2A
C1–C2–H2B
C3–C2–H2A
C3–C2–H2B
H2A–C2–H2B
C5–C6–H6
111
N2–C1–C5
111
111.1192
111.1388
111.1504
109.0771
119.8255
119.8525
119.8255
119.8779
120.0649
120.0737
119.8437
119.7587
119.7064
119.7193
119.4299
119.4083
120.0312
120.0092
119.8725
119.8804
119.4394
119.4374
117.9156
117.8953
118.5812
118.5908
120.4325
120.4488
120.3923
120.3914
C1–C2–C3
111
N1–C3–C11
C2–C3–C11
N1–C3–C2
111
109
120
O1–C4–C17
N2–C4–C17
O1–C4–N2
C7–C6–H6
120
118.66 (19)
120.10 (19)
119.70 (17)
118.52 (19)
121.76 (19)
120.3 (2)
C6–C7–H7
120
C8–C7–H7
120
C1–C5–C10
C6–C5–C10
C1–C5–C6
C7–C8–H8
120
C9–C8–H8
120
C8–C9–H9
120
C5–C6–C7
C10–C9–H9
C5–C10–H10
C9–C10–H10
C11–C12–H12
C13–C12–H12
C12–C13–H13
C14–C13–H13
C14–C15–H15
C16–C15–H15
C11–C16–H16
C15–C16–H16
N3–C18–H18
C17–C18–H18
N3–C19–H19
C20–C19–H19
C19–C20–H20
C21–C20–H20
C17–C21–H21
C20–C21–H21
120
C6–C7–C8
120.3 (2)
120.2906
119.8613
120.3976
120.5743
120.9486
121.1293
117.8976
121.1618
119.9597
116.9605
123.461
120
C7–C8–C9
119.9 (2)
120
C8–C9–C10
C5–C10–C9
C3–C11–C12
C3–C11–C16
C12–C11–C16
C11–C12–C13
C12–C13–C14
O2–C14–C13
O2–C14–C15
C13–C14–C15
C14–C15–C16
C11–C16–C15
C4–C17–C21
C18–C17–C21
C4–C17–C18
120.4 (3)
119
120.6 (2)
119
120.95 (19)
121.13 (17)
117.9 (2)
120
120
120
121.2 (2)
120
119.96 (19)
116.96 (19)
123.5 (2)
119
119
118
119.6 (2)
119.576
118
120.3 (2)
120.2471
121.1232
118.9544
117.2792
123.6747
119
121.12 (19)
118.96 (19)
117.28 (18)
123.7 (2)
119
120
120
120
120
from the experimental structure as shown in the Fig. 11.
This deviation might be because of the molecular geometry
of the structures are derived from two different phases,
experimental structure from the crystalline state and the
optimized structure from the gaseous state and also in the
optimized structure intermolecular interactions with the
surrounding is absent whereas it is there in the experi-
mental structure. The structural parameters, such as bond
length and bond angle of I and II of both experimental and
calculated values are given in the Tables 6, 7, 8, 9, 10 and
11, which shows the optimized structure is in well agree-
ment with the experimental structure.
123

J Chem Crystallogr
B3LYP/6-311G (d,p)
Table 9 Comparison of experimental and calculated bond angles (°) of II
Atoms
Angle (°)
Atoms
Angle (°)
SCXRD
B3LYP/6-311G (d,p)
SCXRD
C2–C1–C5
112.6942
109.9245
109.9256
100.6714
113.3714
109.9233
102.5538
111.2503
111.2491
111.2643
111.2528
109.1704
123.6272
113.9072
122.4653
122.06
112.70 (14)
110.00
C13–C12–H12
C12–C13–C14
C12–C13–H13
C14–C13–H13
C13–C14–C15
O2–C14–C13
O2–C14–C15
C14–C15–C16
C14–C15–H15
C16–C15–H15
C11–C16–C15
C11–C16–H16
C15–C16–H16
C4–C17–C18
C4–C17–C21
C18–C17–C21
C17–C18–H18
N3–C18–C17
N3–C18–H18
C20–C19–H19
N3–C19–C20
N3–C19–H19
C19–C20–C21
C19–C20–H20
C21–C20–H20
C17–C21–C20
C17–C21–H21
C20–C21–H21
C6–C22–H22A
C6–C22–H22B
C6–C22–H22C
H22A–C22–H22B
H22A–C22–H22C
H22B–C22–H22C
N2–N1–C3
119.3453
120.2417
119.8766
119.8817
119.1527
117.5808
123.2384
119.9264
120.0415
120.0321
121.952
119.00
C2–C1–H1
C5–C1–H1
N2–C1–C2
N2–C1–C5
N2–C1–H1
C1–C2–C3
120.24 (17)
120.00
110.00
100.67 (13)
113.37 (13)
110.00
120.00
119.15 (16)
117.58 (16)
123.24 (16)
119.93 (17)
120.00
102.55 (13)
111.00
C1–C2–H2A
C1–C2–H2B
C3–C2–H2A
C3–C2–H2B
H2A–C2–H2B
C2–C3–C11
N1–C3–C2
N1–C3–C11
N2–C4–C17
O1–C4–C17
O1–C4–N2
C1–C5–C6
111.00
111.00
120.00
111.00
121.95 (17)
119.00
109.00
119.0203
119.0277
127.6991
115.1056
117.09
123.63 (15)
113.91 (15)
122.47 (15)
122.06 (15)
119.19 (15)
118.75 (15)
119.60 (14)
120.98 (15)
119.33 (16)
118.23 (15)
122.28 (16)
119.49 (15)
121.53 (17)
119.00
119.00
127.70 (15)
115.11 (15)
117.09 (15)
118.00
119.1929
118.747
118.0205
123.9779
118.0016
118.1988
123.5895
118.2117
118.8104
120.5862
120.6033
119.6098
120.1995
120.1907
109.4701
109.4663
109.4792
109.4679
109.4738
109.47
123.98 (16)
118.00
119.5978
120.9745
119.334
C1–C5–C10
C6–C5–C10
C5–C6–C7
118.00
123.59 (18)
118.00
118.2271
122.2777
119.4925
121.5335
119.2308
119.2357
119.8735
120.0656
120.0608
119.7933
120.1093
120.0974
121.2133
119.3856
119.4011
122.3436
120.22.3
117.3926
121.3208
119.3339
C5–C6–C22
C7–C6–C22
C6–C7–C8
118.8 (2)
121.00
121.00
C6–C7–H7
C8–C7–H7
C7–C8–C9
119.61 (19)
120.00
119.00
119.88 (19)
120.00
120.00
C7–C8–H8
C9–C8–H8
C8–C9–C10
C8–C9–H9
C10–C9–H9
C5–C10–C9
C5–C10–H10
C9–C10–H10
C3–C11–C12
C3–C11–C16
C12–C11–C16
C11–C12–C13
C11–C12–H12
109.00
120.00
109.00
119.79 (18)
120.00
109.00
109.00
120.00
109.00
121.22 (17)
119.00
109.00
107.5731
121.2052
112.8097
125.9309
116.9142
109.4783
107.58 (13)
121.21 (14)
112.81 (12)
125.93 (13)
116.91 (16)
109.00
119.00
C1–N2–C4
122.34 (16)
120.22 (15)
117.40 (16)
121.32 (17)
119.00
N1–N2–C1
N1–N2–C4
C18–N3–C19
C14–O2–H2
Lattice Energy Calculation by PIXELC Module
were obtained and the energy partition showed that the maxi-
mum contribution (*90 %) for the lattice stabilization arises
fromthedispersionenergyforboththecompoundsandalsothe
methyl substitution in ortho position of the phenyl ring in II
changes the total energy by participating in the dispersion and
The total lattice energy of the title compounds were calculated
using PIXELC. The contribution of different energies such as
coulombic, polarization, dispersion and repulsion components
123

J Chem Crystallogr
Table 10 Comparison of experimental and calculated Torsion angles (°) of I
Atoms
Angle (°)
Atoms
Angle (°)
SCXRD
B3LYP/6-311G (d,p)
SCXRD
B3LYP/6-311G (d,p)
C3–N1–N2–C1
C3–N1–N2–C4
N2–N1–C3–C2
N2–N1–C3–C11
N1–N2–C1–C2
N1–N2–C1–C5
C4–N2–C1–C2
C4–N2–C1–C5
N1–N2–C4–O1
N1–N2–C4–C17
C1–N2–C4–O1
C1–N2–C4–C17
C19–N3–C18–C17
C18–N3–C19–C20
N2–C1–C2–C3
C5–C1–C2–C3
N2–C1–C5–C6
N2–C1–C5–C10
C2–C1–C5–C6
C2–C1–C5–C10
C1–C2–C3–N1
C1–C2–C3–C11
N1–C3–C11–C12
N1–C3–C11–C16
C2–C3–C11–C12
C2–C3–C11–C16
O1–C4–C17–C18
-8.28 (1)
168.66 (1)
-1.78 (1)
-179.16 (1)
13.95 (1)
-7.4616
173.2247
-1.5254
179.5186
12.4107
O1–C4–C17–C21
N2–C4–C17–C18
N2–C4–C17–C21
C1–C5–C6–C7
-35.99 (1)
-38.64 (1)
144.93 (1)
176.83 (1)
-1.60 (1)
-177.23 (1)
1.24 (1)
-25.5145
-31.2502
153.8172
177.3584
-0.3539
-177.1631
0.5789
C10–C5–C6–C7
-108.25 (1)
-162.93 (1)
74.87 (1)
-109.0128
-168.2449
70.3316
C1–C5–C10–C9
C6–C5–C10–C9
C5–C6–C7–C8
0.32 (1)
-0.1211
0.3762
178.01 (1)
-2.89 (1)
-5.41 (1)
173.68 (1)
-2.25 (1)
2.77 (1)
178.1067
-1.2362
-1.1525
179.5047
-0.6299
1.3742
C6–C7–C8–C9
1.38 (1)
C7–C8–C9–C10
-1.76 (1)
0.44 (1)
-0.1529
-0.3289
179.5914
-0.195
C8–C9–C10–C5
C3–C11–C12–C13
C16–C11–C12–C13
C3–C11–C16–C15
C12–C11–C16–C15
C11–C12–C13–C14
C12–C13–C14–O2
C12–C13–C14–C15
O2–C14–C15–C16
C13–C14–C15–C16
C14–C15–C16–C11
C4–C17–C18–N3
C21–C17–C18–N3
C4–C17–C21–C20
C18–C17–C21–C20
N3–C19–C20–C21
C19–C20–C21–C17
176.61 (1)
-1.61 (1)
-177.08 (1)
1.15 (1)
-179.5414
0.2454
-13.42 (1)
106.99 (1)
81.73 (1)
-11.8034
109.0874
45.4401
0.41 (1)
0.0604
-179.28 (1)
1.30 (1)
179.9066
0.0296
-99.85 (1)
-32.07 (1)
146.34 (1)
10.40 (1)
-136.8683
-68.3302
109.3614
9.0711
178.85 (1)
-1.77 (1)
0.53 (1)
-179.8497
0.02
-0.1614
-175.9438
-1.0787
177.4574
2.071
-172.38 (1)
2.89 (1)
-172.007
-3.1413
176.639
-177.24 (1)
-0.74 (1)
179.92 (1)
3.25 (1)
-178.95 (1)
-174.16 (1)
4.01 (1)
178.0308
-2.1889
149.4182
-0.30 (1)
-2.80 (1)
-0.3552
-1.4147
140.45 (1)
Table 11 Comparison of experimental and calculated Torsion angles (°) of II
Atoms
Angle (°)
Atoms
Angle (°)
SCXRD
B3LYP/6-311G (d,p)
SCXRD
B3LYP/6-311G (d,p)
C3–N1–N2–C1
C3–N1–N2–C4
N2–N1–C3–C11
N2–N1–C3–C2
C4–N2–C1–C2
N1–N2–C1–C2
C1–N2–C4–O1
N1–N2–C1–C5
C4–N2–C1–C5
C1–N2–C4–C17
N1–N2–C4–O1
N1–N2–C4–C17
C18–N3–C19–C20
C19–N3–C18—C17
C2–C1–C5–C10
-8.28 (1)
169.06 (1)
177.47 (1)
-2.72 (1)
-162.74 (1)
14.74 (1)
-6.6753
173.2193
179.5912
-1.201
O1–C4–C17–C18
C10–C5–C6–C7
C1–C5–C6–C7
162.30 (1)
-1.56 (1)
-178.09 (1)
1.30 (1)
148.1137
0.9327
-178.2654
3.2861
C1–C5–C6–C22
C6–C5–C10–C9
C10–C5–C6–C22
C1–C5–C10–C9
C5–C6–C7–C8
-168.9461
10.953
0.76 (1)
-0.6124
-177.5158
178.6074
-0.5308
177.962
-0.2191
0.5585
177.83 (1)
177.24 (1)
0.95 (1)
-3.80 (1)
-105.86 (1)
76.66 (1)
-0.4516
-110.8381
69.2628
C22–C6–C7–C8
C6–C7–C8–C9
-178.46 (1)
0.52 (1)
176.16 (1)
179.07 (1)
-0.97 (1)
-0.88 (1)
1.04 (1)
-179.5795
179.6621
0.5342
C7–C8–C9–C10
C8–C9–C10–C5
C3–C11–C16–C15
C12–C11–C16–C15
C16–C11–C12–C13
-1.36 (1)
0.72 (1)
-0.145
1.3984
177.18 (1)
-0.48 (1)
0.90 (1)
-179.5895
0.2379
-0.6388
-55.3608
-88.49 (1)
-0.2021
123

J Chem Crystallogr
B3LYP/6-311G (d,p)
Table 11 continued
Atoms
Angle (°)
Atoms
Angle (°)
SCXRD
B3LYP/6-311G (d,p)
SCXRD
N2–C1–C2–C3
C2–C1–C5–C6
N2–C1–C5–C10
N2–C1–C5–C6
C5–C1–C2–C3
C1–C2–C3–C11
C1–C2–C3–N1
C2–C3–C11–C16
N1–C3–C11–C12
C2–C3–C11–C12
N1–C3–C11–C16
N2–C4–C17–C18
N2–C4–C17–C21
O1–C4–C17–C21
-14.55 (1)
87.98 (1)
-10.3441
123.8422
58.3361
C3–C11–C12–C13
C11–C12–C13–C14
C12–C13–C14–C15
C12–C13–C14–O2
C13–C14–C15–C16
O2–C14–C15–C16
C14–C15–C16–C11
C4–C17–C18–N3
C18–C17–C21–C20
C21–C17–C18–N3
C4–C17–C21–C20
N3–C19–C20–C21
C19–C20–C21–C17
-176.72 (1)
-0.25 (1)
-0.83 (1)
177.30 (1)
1.24 (1)
179.6249
0.0599
25.05 (1)
0.0522
-158.48 (1)
106.54 (1)
-168.50 (1)
11.69 (1)
-122.4608
110.1814
-172.9146
7.9018
179.9289
-0.0169
-179.8863
-0.1318
-175.9408
2.0999
-176.79 (1)
-0.58 (1)
-176.55 (1)
-0.26 (1)
-0.49 (1)
176.31 (1)
0.18 (1)
-6.78 (1)
-9.44 (1)
170.77 (1)
173.01 (1)
-17.66 (1)
166.21 (1)
-13.83 (1)
-1.886
-2.5954
178.2918
177.2267
-32.7696
152.3201
-26.7966
-1.0962
177.4617
-0.3673
-1.4298
0.40 (1)
repulsion (Table 12). The stabilization energy from the
selected molecular pair is calculated by using PIXELC and is
given in the Table 13 and it shows that in I O(2)–H(2)ÁÁÁN(3)
(-58.2 kcal/mol) molecular pair is providing the maximum
stability for the crystal packing whereas in II O(2)–H(2)ÁÁÁN(3)
(-62.2 kcal/mol) and C(7)–H(7)ÁÁÁO(1)(-43.4 kcal/mol)
gives the maximum stability (Fig. 12).
Table 12 Lattice energies (kcal/mol) partitioned into coulombic,
polarization, dispersion and repulsion contribution using CLP in I and
II
Compound
Ecol
EPol
EDisp
ERep
ETot
I
-39.6
-37.7
-34.5
-38.2
-190.1
-198.4
70.7
77.4
-193.5
-196.9
II
Table 13 PIXEL interaction
energies (kcal/mol) between
molecular pairs related by a
symmetry operation and the
associated intermolecular
interactions in I and II
Compound Ecol
EPol
EDisp
ERep ETot
Symmetry code
Molecular pairs
I
-72.2 -41.0 -32.7 87.8 -58.2 -x, -1/2 ? y, 1/2 -z
-5.2 -3.4 -10.6 8.5 -10.7 x, 3/2-y, 1/2 ? z
O(2)-H(2)ÁÁÁN(3)
C(19)–H(19)ÁÁÁO(1)
I
II
II
-76.6 -42.5 -42.1 98.5 -62.7 -x, -1/2 ? y, 1/2 - z O(2)–H(2)ÁÁÁN(3)
-28.3 -11.3 -38.9 35.4 -43.4 1-x, -y, -z
C(7)-H(7)…O(1)
Fig. 12 Selected molecular pairs with their interaction energy in the I (a) and II (b)
123

J Chem Crystallogr
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Conclusion
In this study we have demonstrated the results of
experimental single crystal X-ray diffraction, molecular
confirmation by Gaussion09, quantification of inter-
molecular interactions by Hirshfeld surface analysis,
Molecular Electrostatic Potential (MEP) calculation at
B3LYP/6-311 G (d,p) level and the lattice energy cal-
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