Synthesis, crystal structure, hydrogen bonding interactions analysis of novel acyl thiourea derivative

Article abstract of DOI:10.1002/poc.4016

The N-(p-methoxybenzoyl)-N′-(2,4-dinitrophenyl amino)thiourea has been synthesized and characterized by FT-IR, ¹H NMR, and elemental analyses techniques. Also, its molecular structure was determined by single-crystal X-ray diffraction. It revealed that the title compound crystallizes with two unique molecules in the asymmetric unit of the orthorhombic unit cell, space group Pna2(1) with a = 18.857(5) ?, b = 8.148(2) ?, c = 22.443(6) ?, β = 90.00°, C₁₅H₁₃N₅O₆S, M_r = 391.36, V = 3448.2(15) ?³, Z = 8, D_c = 1.508 g·cm^?1, F(000) = 1616, μ = 0.233 mm^?1, S = 1.06, the final R = 0.0626, and wR (I > 2?(I)) = 0.1392. Intramolecular N H … N, C H … N, and N H … O hydrogen bonds indicate that the molecule conformation was mostly planar. Crystal structure stacking through the N H … O, C H … O, and N H … S hydrogen bonds, and two π … π interactions arrangement revealed their conspicuous role in the stabilization of the molecular structure. The type and nature of intermolecular interactions in the crystal structure were investigated by Hirshfeld surfaces and their associated two-dimensional fingerprint plots. Furthermore, shape index and curvedness surfaces further confirmed π … π stacking interactions with different features of molecule A and B. More importantly, the reduced density gradient (RDG) function provides a real-space function for discussing noncovalent interactions (NCI) in title compound, including van der Waals interactions and C H … π contacts in addition to hydrogen bonding interactions within molecule.

Full text of DOI:10.1002/poc.4016

Received: 21 June 2019
DOI: 10.1002/poc.4016
Revised: 6 August 2019
Accepted: 27 August 2019
R E S E A R C H A R T I C L E
Synthesis, crystal structure, hydrogen bonding interactions
analysis of novel acyl thiourea derivative
1
2
3
1
Xing Zhang | Xiaoli Du | Jirong Song | Jie Huang
1
School of Chemical Engineering,
Abstract
Northwest University/Shaanxi key
0
Laboratory of Physico-Inorganic
Chemistry, Xi'an, Shaanxi, China
The N-(p-methoxybenzoyl)-N -(2,4-dinitrophenyl amino)thiourea has been
1
synthesized and characterized by FT-IR, H NMR, and elemental analyses
2
Yuyang District Food Inspection and
techniques. Also, its molecular structure was determined by single-crystal X-
ray diffraction. It revealed that the title compound crystallizes with two unique
molecules in the asymmetric unit of the orthorhombic unit cell, space group
Testing Center, Yulin, Shaanxi, China
3
Ministry of Science and Technology, The
Palace Museum, Beijing, China
ꢀ
Pna2(1) with a = 18.857(5) Å, b = 8.148(2) Å, c = 22.443(6) Å, β = 90.00 ,
Correspondence
3
−1
C H N O S, M = 391.36, V = 3448.2(15) Å , Z = 8, D = 1.508 gꢁcm ,
15
13
5
6
r
c
J. Huang, School of Chemical Engineering,
Northwest University/Shaanxi Key
Laboratory of Physico-Inorganic Chemistry,
Xi'an, Shaanxi 710069, China.
Email: huangjie@nwu.edu.cn
−1
F(000) = 1616, μ = 0.233 mm , S = 1.06, the final R = 0.0626, and wR (I > 2(I))
=
0.1392. Intramolecular N H … N, C H … N, and N H … O hydrogen bonds
indicate that the molecule conformation was mostly planar. Crystal structure
stacking through the N H … O, C H … O, and N H … S hydrogen bonds, and
two π … π interactions arrangement revealed their conspicuous role in the stabili-
zation of the molecular structure. The type and nature of intermolecular interac-
tions in the crystal structure were investigated by Hirshfeld surfaces and their
associated two-dimensional fingerprint plots. Furthermore, shape index and
curvedness surfaces further confirmed π … π stacking interactions with different
features of molecule A and B. More importantly, the reduced density gradient
Funding information
The Natural Science Basic Research of
Shaanxi Province, China, Grant/Award
Number: No. 2018JM2061; The Science
and Technology Program of Shaanxi
Province, China, Grant/Award Number:
No. 2013K02-25; The Science and
Technology Program of Xi’an, China,
Grant/Award Number: No. NC1404; The
Science and Technology Research and
Development Program of Shaanxi
Province, China, Grant/Award Number:
No. 14JF025
(
RDG) function provides a real-space function for discussing noncovalent interac-
tions (NCI) in title compound, including van der Waals interactions and C H … π
contacts in addition to hydrogen bonding interactions within molecule.
K E Y W O R D S
crystal structure, Hirshfeld surface analysis, noncovalent interactions, novel thiourea derivative
1
| INTRODUCTION
acyl thiourea compound, it has a wide range of biological
[
2–4]
[5–7]
activities, such as antiviral,
antimicrobial,
[
8]
[9]
[10,11]
Thiourea has interesting behavior due to its unique com-
bination of functional group, including amino, imino,
herbicidal, antitumor, anti-inflammatory,
and
[
12]
fungicidal properties.
However, an increasing number
[1]
and thiol. Acyl thiourea is a class of important deriva-
tives of thiourea. On the other hand, acyl thiourea deriva-
tives are widely applied in recent decades, such as
heterocyclic synthesis intermediate, non-ionic surfac-
tants, organocatalysts, etc. Further, due to the unique
structure of CO NH CS NH in the structure of the
of people are engaged in researching anticancer drugs as
cancer cases have become more diverse and complex.
Thus, acyl thiourea derivative was also used to study
pharmacological activity through molecular docking
[
3]
methods by our research group. Very recently, supra-
molecular chemistry has developed rapidly, so the
J Phys Org Chem. 2019;e4016.
wileyonlinelibrary.com/journal/poc
© 2019 John Wiley & Sons, Ltd.
1 of 9
https://doi.org/10.1002/poc.4016

2
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ZHANG ET AL.
research of acyl thiourea began to identify supramolecu-
lar anions, and the development of self-assembled mate-
rials has become the focus of the scientific community.
400 MHz using a Bruker spectrophotometer. Elemental
analyses were performed employing an ELEMENTAR
Vario EL III elemental analyzer.
[
13]
In addition, thiourea derivatives are exceptionally versa-
tile ligands in coordination chemistry, due to the exis-
tence of O, S, and N donor atoms in the central thiourea
group moiety; it often facilitates to form complexes with
2
.2 | Synthesis of N-(p-methoxybenzoyl)-
0
N -(2,4-dinitrophenyl amino) thiourea
[14–17]
various transition metals.
The 3D-Hirshfeld surface analysis and 2D fingerprint
[18]
A solution of prepared 4-methoxybenzoyl chloride
(1.7059 g, 10 mmol) in dry tetrahydrofuran (40 mL) was
added dropwise to a three-necked round-bottomed flask
containing potassium thiocyanate (1.4577 g, 15 mmol).
[19]
plots
are becoming effective tools for discussing inter-
molecular hydrogen bonding interactions and maintaining
[20]
self-assembly of supramolecules.
According to recent
The reaction mixture was refluxed for approximately
related literature reports, Hirshfeld surfaces analysis
explains and evaluates intermolecular hydrogen bonding
ꢀ
2
hours at 60 C. A solution of 2,4-dinitrophenylhydrazine
[21,22]
(
2.2329 mL, 9.5 mmol) in tetrahydrofuran (20 mL) was
interactions in a series of thiourea derivatives.
Besides,
ꢀ
ꢀ
the type and intensity of noncovalent interaction (NCI) can
be visually analyzed by electron density and reduced den-
added and reacted in microwave heating 60 C to 65 C for
about 3 minutes. After the reaction was completed, the
resulting mixture in the flask was poured into a beaker
containing 600 mL of cold water and filtered off, washed
with ethanol, and dried in vacuo. A suitable crystal of the
title compound for crystal structure determination was
obtained upon slow evaporation at room temperature
from 15 mL of an organic solvent (ethanol and ethyl ace-
tate = 2: 1) after a week. The synthesis route of the com-
pound was performed according to Scheme 1.
[23,24]
sity gradient (RDG) function.
Apart from the hydrogen
bonding interactions, the NCI analysis reveals the presence
of other weak NCIs such as C H … π lone pair, C H … π
contacts, Van der Waals interactions, and steric hindrance
[25,26]
in the solid state structure of acyl thiourea derivatives.
Thence, the NCIs in the crystal of compound play an
important role in stabilizing molecules with a special mode
[27]
of action, and it is worthwhile to our attention.
Based on the above facts, we intend to report the prep-
The title compound was obtained as white block crys-
tal. Yield: 2.86 g, 87%; m.p.: 189.4 C to 190.7 C; anal.
ꢀ
ꢀ
aration, characterization, and crystal structure of N-(p-
0
methoxybenzoyl)-N -(2,4-dinitrophenyl amino)thiourea.
calcd for C H N O S (M = 391.36): C, 46.03; H,
15
13
5
6
r
Molecular and structural characterization were carried
out by FT-IR, H NMR, and X-ray crystallographic stud-
3
.35; N, 17.89%. Found: C, 46.52; H, 3.48; N, 17.27%. FT-
1
−1
IR (KBr): v, cm 3396/3262 (m, N H stretching), 2979
m, C H stretching), 1676 (s, C O stretching), 760 (s,
ies. In order to precisely quantify those intermolecular
contacts and analyze packing features, we also use the
Hirshfeld surface analysis, 2D fingerprint plots, shape
index, and curvedness properties. Moreover, the NCIs
were investigated by electron density and RDGs.
(
1
C S stretching). H NMR (400 MHz, DMSO-d ): δ 11.68
6
(
s, 1H, NH), 10.56 (s, 1H, NH), 8.89 (s, 1H, Ar H), 8.36
(
s, 1H, Ar H), 8.03 (s, 2H, Ar H), 7.29 (s, 1H, Ar H),
7.02 (s, 2H, Ar H), 3.87 (s, 3H, OCH3).
2
2
| EXPERIMENTAL
.1 | Measurements and instruments
All reagents and solvents for synthesis and analysis were
commercially available obtained from Sigma Aldrich.
Reagents were purified according to the standardization
process and used without further purification. Microwave
synthesis was carried out using a BILON-CW-1000 micro-
wave synthesizer with the appropriate absorption power
setting. The melting point was determined on a Cossim
KER3100-08S apparatus. The FT-IR (KBr pellets) spec-
−
1
trum was recorded in the 4000 to 400 cm range using a
1
Bruker EQUINOX 55 FT-IR spectrometer. The
H
nuclear magnetic resonance (NMR) spectrum of the title
compound was determined in dimethylsulfoxide-d6 at
SCHEME 1 Synthetic route for the synthesis of the target
compound

ZHANG ET AL.
3 of 9
2
.3 | Crystal structure analysis
spectrum of the ligand shows singlet peaks for phenyl
NH proton at 11.68 ppm and the amide NH proton at
A white block crystal with dimensions of 0.37 mm ×
.25 mm × 0.13 mm was chosen for X-ray determination
10.56 ppm, respectively. However, the nitro group is a
0
strong electron-withdrawing group, which can reduce the
electron density of nearby hydrogen nuclei and increase
the hydrogen displacement on the benzene ring. Thus,
the H2 atom was observed as a single peak at 8.89 ppm.
The protons of benzene rings are observed at 7.05 to
analysis. Single crystal X-ray experiment was carried out
by Mo Kα radiation (λ = 0.071073 nm) with Bruker
[28]
APEX-II CCD diffractometer.
generated by the MERCURY program.
7 was used for structure solution and refinement by full-
Molecular structure was
[29]
SHELXS
9
8
3
.03 ppm and the proton of methoxy group appeared at
.87 ppm in the title compound. Surprisingly, H4C atom
2
[30]
matrix least squares on F using the direct methods.
Moreover, the structural stacking diagram of the com-
pound was displayed using a Diamond software program,
and additional geometrical calculations were calculated
may be too active to observe in the hydrogen spectrum of
the acyl thiourea derivative.
[31]
using the program PLATON program.
3.2 | Crystal structure analysis
The title compound crystallized in the orthorhombic sys-
tem with two discrete molecules, A and B, in the asym-
metric unit cell, as is shown in Figure 1. Crystal data,
data collection, and structure refinement details are sum-
marized in Table 1. The selected crystal bond lengths and
bond angle geometric parameters were in the allowed
ranges, as given in Table 2. Interestingly, the properties
of the two molecules are highly similar. However, there
are slight differences between the two molecules mainly
in the partial bond lengths, bond angles and the dihedral
angles of the plane where the respective benzene ring and
pyrimidine ring located. The bond lengths of C(7) N(5)
and C(22) N(10) of the title compound are 1.385(5)
and 1.405(6) Å, respectively. At the same time, the nitro
group [O(3) N(2) O(4)] in structure A has poor planarity
with the benzene ring [C(1) C(6)], whereas the
corresponding O(7) N(6) O(8) in structure B is close to
coplanar with the benzene ring [C(16) C(21)], with dihe-
dral angles between the benzene ring planes and the nitro
2
.4 | Computational details
The plots of the RDG versus the electron density multi-
plied by the sign of the second Hessian eigenvalue sign
(
λ ) were presented by Multiwfn and VMD 1.9.1 soft-
2
[32,33]
ware.
The NCI map is based on a visual index of elec-
tron density and its derivatives, which can effectively
identify and visualize NCI regions in molecular structures.
Consequently, the peaks that appear in the RDG at low
densities correspond to the different NCIs in 2D plots.
3
3
| RESULTS AND DISCUSSION
.1 | Spectroscopic data
The infrared spectra of the title compound showed that
the absorptions of N H groups were located at 3262 to
396 cm− regions. At the same time, the stretching
1
3
−
1
vibration of C S is assigned at 760 cm . The stretching
vibration C O occurred to strongest absorption peaks at
o
o
meanplanes of 12.967 for molecule A and 4.303 for mole-
cule B. Besides, the bond lengths of N(4) C(7), C(7) N(5),
and N(5) C(8) are 1.333(6), 1.385(5), and 1.383(6) Å, which
illustrated a conjugation among the N(3), N(4), C(7), N(5),
676 cm− and a strong 1320, 1243 cm absorption peak,
1
−1
1
which is attributed to the stretching vibration of C N
single bonds in the title compound. In the H NMR
1
FIGURE 1 Molecular structure of the title compound

4
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ZHANG ET AL.
TABLE 1 Crystal data and structure refinement parameters statistic for compound
CCDC
1439535
Chemical formula
Formula weight
Temperature (K)
Wavelength (Å)
a (Å)
15 13 5 6
C H N O S
391.36
296(2)
0.71073
18.857(5)
8.148(2)
22.443(6)
90
b (Å)
c (Å)
α (degree)
β (degree)
γ (degree)
90
90
3
Volume (Å )
3448.2(15)
Z
8
3
Dc (Mg/m )
1.508
Crystal system
Space group
Orthorhombic
Pna2(1)
Index ranges
−18 ≤ h ≤ 22, −8 ≤ k ≤ 9, −26 ≤ l ≤ 26
Absorption coefficient (μ)
F(000)
0.233
1616
o
The range for data collection ( )
1.81 to 25.10
6116
Reflections collected
Independent reflections
3993
R
int
0.075
2
Goodness-of-fit on F (S)
R (all data)
1.062
1 2
R = 0.0626, wR = 0.1392
o
TABLE 2 Selected bond lengths (Å) and bond angles ( )
Bond
Dist.
Bond
Dist.
Bond
Dist.
S(1) C(7)
1.655(5)
1.385(5)
1.333(6)
1.346(6)
1.235(6)
C(7) N(5)
1.385(5)
1.383(6)
1.645(5)
1.393(5)
1.352(6)
C(22) N(9)
C(23) O(11)
C(22) N(10)
C(23) N(10)
1.339(6)
1.214(6)
1.405(6)
1.382(7)
N(3) N(4)
C(8) N(5)
C(7) N(4)
S(2) C(22)
C(6) N(3)
N(8) N(9)
C(8) O(5)
C(21) N(8)
Angle
o
o
o
Angle
( )
( )
Angle
( )
C(8) N(5) C(7)
N(4) C(7) S(1)
C(6) N(3) N(4)
N(5) C(8) O(5)
128.9(4)
123.8(4)
121.3(4)
120.8(5)
O(5) C(8) C(9)
C(5) C(6) N(3)
C(23) N(10) C(22)
N(9) C(22) S(2)
121.9(5)
119.9(4)
127.3(5)
124.6(4)
C(21) N(8) N(9)
120.0(4)
122.2(5)
121.2(5)
123.2(5)
N(10) C(23) O(11)
O(11) C(23) C(24)
C(20) C(21) N(8)
and C(8) atoms. Meanwhile, the N(8) N(9), N(9) C(22),
C(22) N(10), and N(10) C(23) bond lengths (see Table 1)
indicate that the N(8), N(9), C(22), N(10), and C(23) atoms
have conjugate relations. Therefore, the compounds are
sufficiently similar for their molecular structures to be dis-
cussed together.

ZHANG ET AL.
5 of 9
Intramolecular and intermolecular hydrogen bond
parameters are listed in Table 3. It is not difficult to find
that the compound possesses intramolecular N(3) H
shown in Figure 1. The packing diagram of the synthe-
sized compound is depicted in Figure 2. The crystal struc-
ture of the title compound has a pair of N HꢁꢁꢁS
hydrogen bonds, corresponding to the N(8) H(8)ꢁꢁꢁS
(1) (x, −1 + y, 1 + z) and N(3) H(3)ꢁꢁꢁS(2) (x, y, −1 + z)
intermolecular hydrogen bond forming R2 2(10) closed
ring motif (expressed with a red dotted line). Two
molecules in the asymmetric unit are also stabilized by
N(5) H(5C)ꢁꢁꢁO(10) (x, y, 1 + z) and N(8) H(8)ꢁꢁꢁS(1)
generating with an R2 2(10) closed ring motif (expressed
with a blue dotted line). In addition, O(10) atom acts as a
receptor and is connected to form R1 2(7) ring motif
(
3)ꢁꢁꢁO(1), N(4) H(4C)ꢁꢁꢁO(5), N(9) H(9)ꢁꢁꢁO(11), and
N(8) H(8)ꢁꢁꢁO(10) hydrogen bonds that form six-
membered rings and contribute to the relative planarity
of the thiourea central part skeleton. Moreover, an intra-
molecular hydrogen bond has been observed between C
and N atoms [C(5) H(5)ꢁꢁꢁN(4), C(16) H(16)ꢁꢁꢁN(9)], as
TABLE 3 Hydrogen-bond geometry for the title compound
ꢀ
(
Å and )
(expressed with a pink dotted line) by two types of inter-
d
d
d
∠
molecular hydrogen bonds C(14) H(14)ꢁꢁꢁO(10) (x, y, 1 + z)
and N(5) H(5C)ꢁꢁꢁO(10), respectively. They further
encapsulate in the case larger R2 2(10) ring motif
D HꢁꢁꢁA
(D H) (HꢁꢁꢁA) (DꢁꢁꢁA) (D HꢁꢁꢁA)
N(3) H(3)ꢁꢁꢁO(1)
N(3) H(3)ꢁꢁꢁN(1)
N(4) H(4C)ꢁꢁꢁO(5)
N(8) H(8)ꢁꢁꢁN(7)
N(8) H(8)ꢁꢁꢁO(10)
N(9) H(9)ꢁꢁꢁO(11)
C(5) H(5)ꢁꢁꢁN(4)
C(16) H(16)ꢁꢁꢁN(9)
N(10) H(10C)ꢁꢁꢁO(1)
C(11) H(11)ꢁꢁꢁO(11)
C(14) H(14)ꢁꢁꢁO(10)
C(15) H(15B)ꢁꢁꢁO(3)
C(16) H(16)ꢁꢁꢁO(4)
C(25) H(25)ꢁꢁꢁO(1)
0.86
0.86
0.86
0.86
0.86
0.86
0.93
0.93
0.86
0.93
0.93
0.96
0.93
0.93
0.93
0.86
0.93
0.86
0.86
1.97 2.591(6)
2.61 2.916(7)
1.92 2.598(5)
2.61 2.904(7)
1.97 2.596(6)
1.91 2.585(6)
2.46 2.783(7)
2.40 2.737(7)
2.43 3.258(6)
2.48 3.369(7)
2.55 3.442(7)
2.46 3.273(7)
2.59 3.237(8)
2.53 3.437(7)
2.51 3.405(6)
2.66 3.299(4)
2.58 3.202(7)
2.51 3.330(6)
2.68 3.298(5)
128
103
134
102
128
134
100
101
161
159
160
142
127
164
160
132
125
159
129
(
(
expressed with a green dotted line) via the N(10) H
10C)ꢁꢁꢁO(1) (x, y, −1 + z) and N(3) H(3)ꢁꢁꢁS(2) hydrogen
bonds linking adjacent A and B molecules. Apart from
this series of intermolecular contacts, the two molecules
were also stabilized through πꢁꢁꢁπ stacking contacts,
respectively, as shown in Figure S1. The center Cg(1) Cg
(
2) [Cg(1):C(1) C(6), Cg(2):C(9) C(14)] distance is
ꢀ
3.682 in the molecule structure A. Similarly, the ben-
zene ring in structure B is interlaced with the benzene
ring in the compound of the adjacent layer, and the cen-
ter Cg(3) Cg(4) [Cg(3):C(16) C(21), Cg(4):C(24) C(29)]
distance is 3.698 that corresponds to forming a face-to-
a
b
ꢀ
ꢀ
ꢀ
c
o
d
face πꢁꢁꢁπ stacking interactions (see Figure S1). Therefore,
abundant hydrogen bonding could be formed in the crys-
tal structure, and the presence of these intramolecular
and intermolecular hydrogen bonds made the title com-
pound more stable.
Symmetry codes: (a) x, 1 + y, −1 + z; (b) 2 − x, 1 − y,
0.5 + z; (c) x, y, 1 + z; (d) 1 + x, y, z; (e) 1.5 − x, 0.5 + y,
−0.5 + z; (f) x, −1 + y, 1 + z; (g) 2 − x, 2 − y, 0.5 + z;
e
a
e
C(28) H(28)ꢁꢁꢁO(5)
N(3) H(3)ꢁꢁꢁS(2)
C(4) H(4)ꢁꢁꢁO(7)
N(5) H(5C)ꢁꢁꢁO(10)
f
g
c
h
N(8) H(8)ꢁꢁꢁS(1)
(
h) x, y, −1 + z
FIGURE 2 Packing diagrams of
the title compound viewed along the
b-axis

6
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ZHANG ET AL.
3
.3 | Hirshfeld surface analysis
(a). The SꢁꢁꢁH/HꢁꢁꢁS (10.5%) contacts with a pair of
sharper spikes center near to a sum of (d + d ) 2.5 Å
i
e
In order to understand the title compound interactions
within the crystal structure, the Hirshfeld surface anal-
ysis and their associated 2D fingerprint plot were
performed
software.
are presented in Figure S2, which are attributed to the
N(8) H(8)ꢁꢁꢁS(1) and N(3) H(3)ꢁꢁꢁS(2) hydrogen bond
interactions. The OꢁꢁꢁH/HꢁꢁꢁO (3.7%) contacts with a pair
of sharp spikes center near to a sum of (d + d ) values
using
CrystalExplorer
3.1
program
i
e
[
34–36]
were about 2.3 and 2.5 Å in the fingerprint plots. Interest-
ingly, the OꢁꢁꢁH/HꢁꢁꢁO contacts contributed the most to
the entire Hirshfeld surfaces of the title compound. The
conventional HꢁꢁꢁH contacts contribute 18.4% on the
Hirshfeld surface with a pair of sharp spikes between
The Hirshfeld surfaces mapped over the dnorm were
seen in Figure 3. From the view of dnorm surfaces for the
title compound, some red areas could be observed. The
dnorm map shows red regions labeled 1 for molecule A,
labeled 6 for molecule B, which demonstrate strong
N HꢁꢁꢁS [N(8) H(8)ꢁꢁꢁS(1) and N(3) H(3)ꢁꢁꢁS(2)] inter-
molecular hydrogen bonding interactions. The two red
regions labeled 2 and 5 in the dnorm map are attributed
to N HꢁꢁꢁO contacts, which is N(5) H(5C)ꢁꢁꢁO(10) and
N(10) H(10C)ꢁꢁꢁO(1) hydrogen bonding interactions.
Similarly, we observe red regions appear near to the car-
bon atom (labeled 3 and 4), which correspond to inter-
molecular C(11) H(11)ꢁꢁꢁO(10) and C(25) H(25)ꢁꢁꢁO(1)
hydrogen bond interactions. For molecule A, the lightest
red region (labeled 7) is attributed to the C(4) H(4)ꢁꢁꢁO
(
d + d ) 2.1 and 2.3 Å. However, Figure S2 depicted that
i e
CꢁꢁꢁC contacts (4.9%) appear at spikes center near to a
sum of (d + d ) 2.4 and 2.5 Å, which is due to the πꢁꢁꢁπ
i
e
stacking interactions in the molecules. Besides, the
NꢁꢁꢁH/HꢁꢁꢁN (1.5%) and CꢁꢁꢁH/HꢁꢁꢁC (10.0%) inter-
molecular contacts also contribute to the Hirshfeld sur-
faces, as shown in Table S1.
The shape index and curvedness properties generally
used to identify planar stacking arrangements were per-
formed in the compound A and B, respectively, as shown
in Figure 4. For molecular structure A, the red-blue trian-
gles were presented in phenyl regions [C(1)-C(6)] of
shape index, which indicated that the entire surface is
πꢁꢁꢁπ stacking interactions with adjacent molecular. At
the same time, the red-blue triangle appears in the ben-
zene ring [C(16)-C(21)] region of the compound structure
B, which is due to the presence of πꢁꢁꢁπ stacking interac-
tions between the adjacent two molecules (seen in
Figure S1). It can be observed in Figure 4, the flat regions
of the curvedness surface also indicate the πꢁꢁꢁπ stacking
interactions. Therefore, apart from these nonclassic
hydrogen bonds, CꢁꢁꢁC contacts atoms of the molecule
inside the surface of the synthesized compound A and
B also attribute to the πꢁꢁꢁπ stacking interactions, as
shown in Figure S2 (g).
(
7) contacts. The CꢁꢁꢁO contacts attributed to C(14) H
(14)ꢁꢁꢁO(10) and C(15) H(15B)ꢁꢁꢁO(3) hydrogen bonds can
be seen as the two red regions labeled 8 and 9. Meanwhile,
the red regions occur near to the O and C atoms in the
compound B, respectively, which are due to form C(11)
H(11)ꢁꢁꢁO(11) and C(28) H(28)ꢁꢁꢁO(5) intermolecular
hydrogen bonding interactions (labeled 10 and 11) with
adjacent molecules.
Fingerprint plots in Figure S2 revealed the inter-
molecular interaction patterns and the relative contribu-
tions to the Hirshfeld surface of the synthesized
compound. The upper spike (labeled 1) corresponds to
the donor spike, while the lower spike (labeled 2) corre-
sponds to an acceptor spike, as illustrated in Figure S2
FIGURE 3 Hirshfeld surfaces dnorm for
molecules A and B

ZHANG ET AL.
7 of 9
FIGURE 4 The shape index (the left) and curvedness (the right) for molecules A and B
3
.4 | Noncovalent interaction analysis
were shown in Figure 6. For the title compound, red fusi-
form shapes were observed in the central regions of the
two benzene rings, respectively (Figure 5). It reflected
strong steric effect between the benzene rings,
corresponding to a clear peak on the scatter plot
The NCI theory identifies interactions as areas of low
electron density (ρ) and low RDGs. The RDG function is
usually used to better understand and highlight the
regions involved in the weak interaction in the whole
molecular system, so as to intuitively analyze which
regions are related to the weak interactions. This weak
interaction was distinguished by the values of sign (λ )ρ
and color coded, whereas the sign (λ )ρ function is the
symbol of the second largest eigenvalue λ of the electron
(
Figure 6). There is a blue isosurface between the nitro-
gen atom and the oxygen atom. It belongs to the
N HꢁꢁꢁO strong hydrogen bonding interaction, which
2
corresponds to −0.040 a.u. < sign (λ )ρ < −0.032 a.u. in
2
2
the 2D NCI plot. The N HꢁꢁꢁN and C HꢁꢁꢁN hydrogen
2
bond contacts displayed the low gradient low density
density Hessian matrix. Blue isosurfaces show the strong
attractive interaction such as hydrogen bond and strong
halogen bond. Conversely, green areas indicate the wea-
ker interactions such as vdW contacts, and the red
regions exhibit strong mutual exclusion interactions.
The NCI analysis has been performed to identify inter-
actions in hydrogen bonded compound, while this weak
interaction of the title compound is generated and repre-
sented by the 2D NCI map and the 3D isosurface. The 3D
isosurface plot was given in Figure 5, and the spikes of
interaction with values of −0.040 a.u. < sign (λ )ρ <
2
−
0.030 a.u. and −0.020 a.u. < sign (λ )ρ < −0.015 a.u.,
2
respectively, as shown in Figure 6. There is a low density
domain coming from C HꢁꢁꢁO C attractive interactions
in the range of −0.040 a.u. to −0.030 a.u.. This is in good
[25]
agreement with the previously reported results.
In par-
ticular, an area of flat bicolored proved that attractive
and exclusive interactions synchronously existed between
S and H atoms, as shown in Figure 5. It was worth noting
that the weak vdW interactions appeared at the position
2
D NCI plot of the reduced gradient values sign (λ )ρ
2
where −0.005 a.u. < sign (λ )ρ < 0.005 a.u., as shown in
2
FIGURE 5 The title compound 3D
gradient isosurface structure

8
of 9
ZHANG ET AL.
of Xi'an, China (No. NC1404), and the Science and Tech-
nology Research and Development Program of Shaanxi
Province, China (No. 14JF025) and the Natural Science
Basic
Research
of
Shaanxi
Province,
China
(
No. 2018JM2061)
ORCID
Jie Huang https://orcid.org/0000-0003-3561-2819
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