Synthesis of novel benzohydrazide and benzoic acid derivatives: Crystal Structure, Hirshfeld surface analysis and DFT computational studies

Article abstract of DOI:10.1016/j.molstruc.2021.130465

New series of benzohydrazide/benzoic acid derivatives were synthesized (4a-b and 5a-b) and subjected to solid-state characterization by NMR spectroscopic measurements. The molecular and crystal structures of 4a and 5a have also been examined by single-crystal X-ray crystallography were reveal that naphthalene frameworks are close to planarity. Besides, the dihedral angle between the mean plane of the naphthalene ring system and the phenyl ring is 2.26(7) and 78.87(8)° for 4a and 5a, respectively. The molecules are linked through N—H?O and C—H?O hydrogen bonds, forming chains parallel to the ab plane in benzohydrazide and O—H?O contacts in benzoic acid. The sheets are further stacked through C—H?π interactions resulting in the formation of a 3D supramolecular network. Hirshfeld surface analysis has also been performed to investigate intermolecular interactions in the solid-state; the most important contributions for the crystal packing are from H?H, C?H/H?C, and O?H/H?O interactions. Additionally, DFT calculations with the B3LYP/6-311G (d, p) level of the theory have been used to analyze the Mulliken atomic charges, molecular electrostatic potential map, and non-linear optical properties of the compounds were produced using the optimized structures. Moreover, the natural bond orbital analysis is conducted to explore the interactions among different orbital and lone pairs taking place within the compounds. The energy framework calculations suggest that the contacts formed between molecules are largely dispersive.

Full text of DOI:10.1016/j.molstruc.2021.130465

Journal of Molecular Structure 1239 (2021) 130465
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Synthesis of novel benzohydrazide and benzoic acid derivatives:
Crystal Structure, Hirshfeld surface analysis and DFT computational
studies
a,b,∗
a
b,∗
Sofia Zazouli
, Latifa Lâallam , El Mostafa Ketatni
a
Laboratory of Sustainable Development, Sultan Moulay Slimane University, Faculty of Sciences and Technology, B.P.523, 23000, Beni Mellal, Morocco
Laboratory of Organic and Analytical Chemistry, University Sultan Moulay Slimane, Faculty of Science and Technology, B.P.523, 23000, Beni-Mellal,
b
Morocco
a r t i c l e i n f o
a b s t r a c t
Article history:
New series of benzohydrazide/benzoic acid derivatives were synthesized (4a-b and 5a-b) and subjected
to solid-state characterization by NMR spectroscopic measurements. The molecular and crystal structures
of 4a and 5a have also been examined by single-crystal X-ray crystallography were reveal that naph-
thalene frameworks are close to planarity. Besides, the dihedral angle between the mean plane of the
naphthalene ring system and the phenyl ring is 2.26(7) and 78.87(8)° for 4a and 5a, respectively. The
molecules are linked through N—HꢀO and C—HꢀO hydrogen bonds, forming chains parallel to the ab
plane in benzohydrazide and O—HꢀO contacts in benzoic acid. The sheets are further stacked through C—
Hꢀπ interactions resulting in the formation of a 3D supramolecular network. Hirshfeld surface analysis
has also been performed to investigate intermolecular interactions in the solid-state; the most important
contributions for the crystal packing are from HꢀH, CꢀH/HꢀC, and OꢀH/HꢀO interactions. Addition-
ally, DFT calculations with the B3LYP/6-311G (d, p) level of the theory have been used to analyze the
Mulliken atomic charges, molecular electrostatic potential map, and non-linear optical properties of the
compounds were produced using the optimized structures. Moreover, the natural bond orbital analysis
is conducted to explore the interactions among different orbital and lone pairs taking place within the
compounds. The energy framework calculations suggest that the contacts formed between molecules are
largely dispersive.
Received 9 February 2021
Revised 30 March 2021
Accepted 1 April 2021
Available online 14 April 2021
Keywords:
Crystal structure
Naphthalene
Benzohydrazide
Schiff base
Intermolecular interactions
Hirshfeld surface analysis
DFT
NBO
©
2021 Elsevier B.V. All rights reserved.
1
. Introduction
pounds, and naphthalene derivatives have been reported as micro-
tubule inhibitors, apoptosis inducers, glutamamide analogues, or P-
glycoprotein inhibitors agent [10-12]. Several naphthalene deriva-
tives were also shown to have anti-arrhythmia, anti-tumor, and an-
tioxidant activities [13] and allylamines (e.g., naftifine, terbinafine)
have been commercialized for the treatment of fungal infections
[14,15].
Substituted benzoic acid or benzohydrazide derivatives are an
important class of compounds with many interesting features, in-
cluding biological and pharmacological activities, as well as suit-
ability for analytical applications. In this regard, many benzohy-
drazide derivatives have been synthesized and reported to have
a variety of biological activities such as antimicrobial [1-3], anti-
cancer [2,4,5], and antiarrhythmic [6]. Besides, benzohydrazides are
easily converted into hydrazones by treating with aldehydes or ke-
tones [7-9].
Hydrazides are acylated derivatives of hydrazine that have
gained great interest due to their broad range of biological sig-
nificance, particularly in medicinal and enzyme chemistry [16].
Further, hydrazides having an azomethine –NH–N=CH– group
attached to the carbonyl group constitutes an important key
role in heterocyclic chemistry [17]. In recent years, hydrazides
derivative was described as an effective and selective inhibitor
for antibacterial [18], anti-convulsant [19,20], anti-analgesic [21],
anti-inflammatory [22], anti-platelet [23], antimalarial [24], anti-
tumoral [25], antiviral [26,27], anti-tubercular [28], antiprolifera-
tive [29], and antioxidant [30,31]. Also, hydrazides or carboxylic
Naphthalene ring is considered as one of the most important
scaffolds and is embedded in many pharmaceutically active com-
∗
Correspondence e-mail address: Sofia Zazouli and El Mostafa Ketatni, Laboratory
of Organic and Analytical Chemistry, University Sultan Moulay Slimane, Faculty of
Science and Technology, B.P.523, 23000, Beni-Mellal, Morocco
E-mail addresses: sofia.zazouli@usms.ma (S. Zazouli), elm_ketatni@hotmail.fr
(
E.M. Ketatni).
https://doi.org/10.1016/j.molstruc.2021.130465
022-2860/© 2021 Elsevier B.V. All rights reserved.
0

S. Zazouli, L. Lâallam and E.M. Ketatni
Journal of Molecular Structure 1239 (2021) 130465
acid commonly serve as intermediates and as starting materials for
the synthesis of surfactants and pharmaceutical products [32,33].
Given the above importance of compounds, our attention
122.0, 120.8, 114.2, 105.0, 66.7, 60.7, 14.4. Elemental analysis (%):
C21H20O4 calculated: C 74.98; H 5.99; found: C 75.01, H 5.97.
has attracted to design and synthesize
a
series of benzohy-
2.2.2.2. Ethyl 4-(2-phenoxyethoxy)benzoate (3b). White solid, 3.65 g,
drazide/benzoic acid derivatives (4a, 4b, 5a, and 5b), characterized
by 1H and 13C NMR spectroscopy and elemental analysis. Further,
the structural properties of compounds 4a and 5a have been elu-
cidated using single-crystal X-ray crystallography. The work also
involves the computational studies with Hirshfeld surface analysis
and density functional theory (DFT, at B3LYP/6-311G (d, p) level).
93% yield. 1H-NMR (CDCl , 300MHz): δ (ppm) = 8.32 – 8.21 (m,
3
2H), 7.62 – 7.48 (m, 2H), 7.30 – 7.16 (m, 5H), 4.69 – 4.54 (m, 6H),
1
3
1.64 (t, J = 7.1 Hz, 3H). C-NMR (CDCl , 75MHz): δ (ppm) = 166.3,
3
162.3, 158.4, 131.5, 129.5, 123.3, 121.2, 114.6, 114.1, 66.6, 66.2, 60.6,
14.3. Elemental analysis (%): C17 H18 O4 calculated: C 71.31; H 6.34;
found: C 71.30, H 6.32.
2. Experimental
2.2.3. Synthesis of compounds 4a and 4b
A solution of compound 3a (5g, 14.8 mmol) or 3b (3.5g, 12.2
mmol), in a mixture of EtOH (25 mL) and aq. KOH (3 M, 25 mL)
was heated for 4h at 90°C, before it was allowed to reach RT.
The organic solvent was removed under reduced pressure, and the
aqueous solution was then acidified (pH 1) with HCl (6 M). The
resulting white precipitate was collected by filtration, washed with
2
.1. Materials and methods
The starting materials and solvents were purchased from com-
mercial suppliers and used without further purification. 1H- and
13C-NMR spectra were recorded at 298 K on either Bruker AV300
or Bruker AV500 spectrometers in deuterated solvents and the
residual solvent peak was used as the internal reference. All the
chemical shifts (δ) are reported in ppm.
H O (100 ml), and dried under vacuum for 24 h to afford com-
2
pounds 4a and 4b in quantitative yield.
2
.2.3.3. 4-(2-(naphthalen-1-yloxy)ethoxy)benzoic acid (4a). White
2
.2. Synthesis
solid, 4.5g quantitative yield. 1H-NMR (DMSO, 500MHz):
δ(ppm) = 8.11 (d, J = 8.3 Hz, 1H), 7.92 (d, J = 8.5 Hz, 2H),
7.87 (d, J = 8.1 Hz, 1H), 7.55 – 7.49 (m, 2H), 7.45 (dt, J = 13.2, 7.9
Hz, 2H), 7.13 (d, J = 8.6 Hz, 2H), 7.05 (d, J = 7.5 Hz, 1H), 4.58 –
4.49 (m, 4H). 13C-NMR (DMSO, 500MHz): δ (ppm) = 167.5, 162.6,
154.2, 134.5, 131.9, 127.9, 126.98, 126.7, 125.8, 125.3, 123.7, 122.0,
120.7, 114.9, 106.0, 67.2, 67.2. Elemental analysis (%): C19 H16 O4
calculated: C, 74.01; H, 5.23; found: C 74.10, H 5.26.
2
.2.1. Synthesis of ethyl 4-(2-(tosyloxy)ethoxy)benzoate (2)
To
a stirred solution of ethyl 4-(2-hydroxyethoxy)benzoate
(
10g, 47.5 mmol) in CH Cl (100 mL) were added DMAP (4-
2
2
Diméthylaminopyridine) (20 mg, 1.6 mmol) and Et N (10 mL, 72
3
mmol). A solution of p-Toluenesulfonyl chloride (13g, 68 mmol)
was added to the mixture in portion-wise over 20 minutes. The
reaction mixture was stirred 24h at RT, and the resulting solution
was washed with aq.NaHCO3 (10 %, 3 × 80 mL) and H O (100 mL).
2.2.3.4. 4-(2-phenoxyethoxy)benzoic acid (4b). White solid, 3.1g
quantitative yield. 1H-NMR (DMSO, 500MHz): δ(ppm) = 7.86 –
7.80 (m, 1H), 7.34 – 7.27 (m, 1H), 7.01 – 6.90 (m, 2H), 4.37 – 4.28
(m, 2H). 13C-NMR (DMSO, 500MHz): δ (ppm) = 168.2, 160.5, 158.8,
131.3, 130.0, 121.2, 114.9, 113.8, 66.8, 66.6. Elemental analysis (%):
C15H14 O4 calculated: C, 69.76; H, 5.46; found: C 69.72, H 5.43.
2
The organic layer was dried over MgSO and the solvent was re-
4
,
moved under reduced pressure. The residue was purified by col-
umn chromatography (SiO , eluent: cyclohexane/CH Cl 4:1 then
2
2
2
1
:1) to give a white solid compound 2 (13 g, 75% yield).
1
H-NMR (CDCl , 500MHz): δ (ppm) = 7.88 – 7.82 (m, 2H), 7.73
3
–
4
4
7.68 (m, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.71 – 6.65 (m, 2H), 4.31 –
.25 (m, 2H), 4.25 (d, J = 7.2 Hz, 1H), 4.22 (d, J = 7.1 Hz, 1H),
2.2.4. Synthesis of compounds 5a and 5b
13
.12 – 4.06 (m, 2H), 2.34 (s, 3H), 1.27 (t, J = 7.1 Hz, 3H). C-
A solution of compound 3a (1g, 3mmol) or 3b (1g, 3.5mmol)
in 10 mL of Hydrazine monohydrate was refluxed (24 h) before it
NMR (CDCl , 500MHz): δ (ppm) = 166.2, 161.5, 145.1, 132.7, 131.5,
3
129.9, 128.0, 123.6, 114.0, 67.8, 65.4, 60.7, 21.7, 14.4. Elemental anal-
was allowed to reach RT. H O (10 mL) was added and the resulting
2
ysis (%): C18 H20O S calculated: C, 59.33; H, 5.53; found: C 59.32, H
white precipitate was collected by filtration, washed with H O (60
6
2
5
.55.
ml), and dried under vacuum for 24 h to afford compounds 5a and
5b as a white solid.
2
.2.2. Synthesis of compounds 3a and 3b
Acetonitrile solution (100 mL) of compound
2
(5 g, 13.7
2.2.4.5. 4-(2-(naphthalen-1-yloxy)ethoxy)benzohydrazide
(5a).
mmol) was degassed with argon before the addition of 1-
Hydroxynaphthalene (4 g, 27.7 mmol) or phenol (2.6 g, 27.6 mmol).
Later (15 min), K CO (4 eq) was added, and the reaction media
White solid, 0.9g in 94% yield. 1H-NMR (DMSO, 500MHz):
δ(ppm) = 9.66 (s, 1H), 8.10 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 8.1
Hz, 1H), 7.84 – 7.79 (m, 2H), 7.54 – 7.39 (m, 4H), 7.09 (d, J = 8.6
Hz, 2H), 7.03 (d, J = 7.5 Hz, 1H), 4.55 – 4.47 (m, 4H), 4.44 (s,
2H). 13C-NMR (DMSO, 500MHz): δ (ppm) = 166.1, 161.2, 154.2,
134.5, 129.3, 127.9, 127.0, 126.7, 126.1, 125.8, 125.3, 122.0, 120.7,
114.7, 106.0, 67.3, 67.1. Elemental analysis (%): C19 H18 N O , H O
2
3
was allowed to stir 48h at reflux under an argon atmosphere. Af-
ter cooling to RT and evaporation of the organic solvent under re-
duced pressure, the residue obtained was dissolved in CH Cl (80
2
2
mL) and washed with a NaOH aqueous solution (5%, 80 mL) and
H O (60 mL). The organic layer was dried over MgSO , and the sol-
2
3
2
calculated: C, 67.05; H, 5.92; N, 8.23; found: C 67.01, H 5.96, N
8.21.
2
4
vent was removed under reduced pressure. The residue was puri-
fied by column chromatography (SiO , eluent: cyclohexane/CH Cl
2
2
2
1
:1 then CH Cl ), yielding the compound 3a and 3b as white solid.
2.2.4.6. 4-(2-phenoxyethoxy)benzohydrazide (5b). White solid, 0.8g
in 84% yield. 1H-NMR (DMSO, 500MHz): δ (ppm) = 9.63 (s, 1H),
7.80 (d, J = 8.8 Hz, 2H), 7.30 (t, J = 7.9 Hz, 2H), 7.04 (dd, J = 9.7,
4.3 Hz, 2H), 6.98 (d, J = 8.1 Hz, 2H), 6.95 (t, J = 7.2 Hz, 1H), 4.68
2
2
2
.2.2.1. Ethyl 4-(2-(naphthalen-1-yloxy)ethoxy)benzoate (3a). White
solid, 4.5 g, 97% yield. 1H-NMR (CDCl , 500MHz): δ (ppm) = 8.51
3
13
–
8.45 (m, 1H), 8.29 – 8.23 (m, 2H), 8.03 (dd, J = 7.9, 1.6 Hz, 1H),
(s, 1H), 4.44 – 4.34 (m, 2H), 4.32 (dt, J = 6.9, 2.8 Hz, 2H). C-
NMR (DMSO, 500MHz): δ (ppm) = 165.9, 160.9, 158.7, 131.7, 130.0,
129.2, 126.1, 121.2, 114.9, 114.5, 66.9, 66.5. Elemental analysis (%):
C15H16 N O , 2H O calculated: C, 58.43; H, 6.54; N, 9.09; found: C
7
.75 – 7.64 (m, 3H), 7.61 (t, J = 7.9 Hz, 1H), 7.26 – 7.20 (m, 2H),
7
.08 (d, J = 7.5 Hz, 1H), 4.72 (s, 4H), 4.59 (q, J = 7.1 Hz, 2H), 1.62
13
(t, J = 7.1 Hz, 3H). C-NMR (CDCl , 500MHz): δ (ppm) =166.4,
3
2
3
2
162.4, 154.3, 134.5, 131.6, 127.4, 126.5, 125.7, 125.6, 125.3, 123.3,
58.40, H 6.59, N 9.11.
2

S. Zazouli, L. Lâallam and E.M. Ketatni
Journal of Molecular Structure 1239 (2021) 130465
Table 1
Crystal data, summary of intensity data collection, and structure refinement.
4a
5a
Chemical formula
C19H16O4
C19H18N2O3
322.35
Mr
308.32
Crystal system, space group
Monoclinic, P21/c
173
Orthorhombic, Pbca
173
Temperature (K)
a, b, c ( A˚ )
14.3640(8), 6.3301(3),17.8517(12),
90, 108.326(2), 90
1540.8 (2)
9.4218(6), 9.7086(7), 36.2335(18),
90, 90, 90
α, β, γ
V ( A˚ 3
)
3314.4 (4)
Z
4
8
Radiation type
Mo Kα
0.09
Mo Kα
0.09
μ(mm 1)
−
Crystal size (mm)
0.10 × 0.09 × 0.09
Prism, colorless
2.4- 28.50
0.08 × 0.08 × 0.08
Prism, colorless
2.437- 26.372
Crystal shape and colour
Theta range for data collection (°)
Limiting indices
-19 ≤h ≤18, -5 ≤ k ≤8, -23 ≤ l ≤ 24
Bruker APEX-II CCD
Multi-scan (SADABS)
0.991, 0.992
-11 ≤h≤11, -12 ≤ k ≤12, -29 ≤ l≤ 40
Bruker APEX-II CCD
Multi-scan (SADABS)
0.994, 0.995
Diffractometer
Absorption correction
Tmin, Tmax
No. of measured, independent and
observed [I > 2σ(I)] reflections
Rint
12127, 3810, 2605
20984, 3192, 1947
0.041
0.064
sin θ/λ)max ( A˚ 1)
−
(
0.676
0.625
R[F2 > 2σ(F )], wR(F ), S
2
2
0.049, 0.121, 1.03
208
0.048, 0.104, 1.01
229
No. of parameters
H-atom treatment
H atoms parameters contrained
H atoms treated by a mixture of
independent and constrained
refinement
max, ꢀρmin (e A˚ 3)
−
ꢀρ
0.26, -0.21
0.15, -0.18
2
.3. Crystal X-ray data collection and refinement
A Bruker APEX-II CCD crystal X-ray diffractometer was used
to collect the X-ray intensities data of crystal compound, using
˚
MoKα radiation (λ = 0.71073A) monochromated by graphite at
173K. The following software was used: Frame integration, Bruker
SAINT Software package, and data were corrected for absorption by
the multi-scan semi-empirical method implanted in SADABS [34].
The crystal structure was solved by direct methods using SHELXTL-
2
014/5 [35] and refined by weighted full matrix least-squares on
F2 data using the SHELXL-2018/3 program [36]. The result of con-
secutive refinements reveals the low-reliability factor (R = 0.049
for 4a and 0.049 for 5a) which reveals that the structure is more
stable. All non-hydrogen atoms were refined with anisotropic ther-
Scheme 1. Synthesis of ethyl 4-(2-(tosyloxy)ethoxy)benzoate (2). Reagents and con-
ditions: i) CH Cl , Et N, DMAP, RT, 24 h.
2
2
3
mal parameters. The C-bound H atoms were geometrically placed
˚
2.5. Quantum chemical calculations
(
C—H = 0.95 – 0.99 A) and refined as riding with Uiso(H) = 1.2
–
1.5Ueq(C). The N/O-bound H atom was located in a difference
Density functional theory (DFT) has proved to be useful for un-
derstanding the electronic structures of compounds 4a-b and 5a-b.
The full molecular geometry optimization of the compound was
performed through the Gaussian 09 W program and GaussView
molecular visualization software package [41,42] on a personal
computer, based on density functional theory DFT, using Beck’s
three parameters hybrid exchange functional, with 6-311G (d, p)
basis sets and Lee-Yang-Parr correlation functional (B3LYP) [43-45].
The optimized structure of each compound has been used to calcu-
late the Molecular Electrostatic Potential (MEP), Mulliken and Nat-
ural Bond Orbital (NBO) charges were determined to investigate
the charge distribution on all compounds( Scheme 1).
Fourier map and refined freely. Crystal data, data collection, and
structure refinement details for 4a and 5a were summarized in
Table 1. The plot of the molecule and the three-dimensional draw-
ing of the crystal structure are obtained using the Diamond pro-
grams [37].
2
.4. Hirshfeld surface and 2D fingerprint plots
The Hirshfeld surfaces calculated for compounds 4a and 5a
were investigated to verify the contributions of the different inter-
molecular interactions between different units in the crystal pack-
ing motif and visualize them graphically. Thus, a Hirshfeld surface
analysis [38] and the associated two-dimensional fingerprint plots
3. Results and discussion
[
39] were performed using CrystalExplorer17.5 [40] to figure out
3.1. Synthesis
the normalized contact distance (dnorm), which depends on contact
distances to the closest atoms outside (de) and inside (d ) the sur-
For the study at hand,
a
series of novel benzoic
i
face. The molecular HS was performed using a standard (high) sur-
face resolution with the three-dimensional surfaces mapped using
a standard surface resolution with a fixed colour scale of -0.7494
to 1.3473 a.u. for 4a and -0.5181 to 1.5707 a.u. for 5a.
acid/benzohydrazide derivatives containing naphthalene ring
were synthesized in three steps as shown in Scheme 2. The
starting materials ethyl 4-(2-(tosyloxy)ethoxy)benzoate (2) was
synthesized via the reaction of ethyl 4-(2-hydroxyethoxy)benzoate
3

S. Zazouli, L. Lâallam and E.M. Ketatni
Journal of Molecular Structure 1239 (2021) 130465
Scheme 2. Synthetic strategy employed for the preparation of 3a-b, 4a-b, and 5a-b. Reagents and conditions: i) K2CO3, CH3CN, reflux, 48h; ii) KOH (3M), EtOH, reflux, 4h;
iii) H2NNH2, reflux, 24h.
with p-Toluenesulfonyl chloride in dichloromethane at room
temperature. The reaction of this compound (2) with 1-
Hydroxynaphthalene or phenol in acetonitrile in the presence
of potassium carbonate at reflux for 48 hours gave, respectively
ethyl 4-(2-(naphthalen-1-yloxy)ethoxy)benzoate (3a) or ethyl
4
-(2-phenoxyethoxy)benzoate (3b). Both compounds (3a or 3b)
were hydrolyzed in basic condition (KOH) in ethanol at reflux
for 4 hours to give final monomers benzoic derivatives 4a or 4b
in quantitative yields. In the case of compound 4b, it had been
previously synthesized (88.8%) from methyl-4-hydroxybenzoate
and methyl-4-(2-phenoxyethoxy)benzoate, and found as promising
high-performance monomers [46], which led us to improve its
yield by a slight change in the reaction condition. When these
compounds (3a or 3b) were reacted with hydrazine at reflux for
24 hours to get two benzohydrazide derivatives in very good to
excellent yields (5b, 84%; 5a, 94%). All of the newly synthesized
compounds were characterized by 1H and 13C NMR, besides the
structures of compounds, 4a and 5a were demonstrated by X-ray
diffraction analysis.
3
.2. Crystal structure of 4a and 5a
The structure of 4a and 5a were confirmed by single-crystal X-
ray diffraction analysis (Fig. 1). Compound 4a crystallizes in the
monoclinic system with P2 /c space group, while crystal of 5a is
1
an orthorhombic Pbca space group with eight molecules in the unit
cell. The hydrogen bonding geometries and experimental geomet-
rical parameters were given in Tables 2 and 3, respectively. The
structural diagrams of both crystal structures consist of naphtha-
Fig. 1. The structures of 4a and 5a showing the atom numbering with ellipsoids
drawn at the 50% probability level.
lene and benzoic acid/ benzohydrazide related by O—CH —CH —
2
2
˚
O group, as shown in Fig. 1. All C—O and C=O bond length slay
for all non-hydrogen atoms of 0.014 A. The phenyl C2—C7 is in-
˚
˚
within the range of 1.292(2) – 1.433(2) A and 1.240(2) – 1.252(2) A,
confirming single and double-bond character, respectively. For 5a,
the C-N and N-N bond lengths range from a typical single bond
clined to the naphthalene system by a dihedral angle of 2.26(7)°.
The O—C—C—O group displays a torsion angle of 177.56(16)°, which
contributes to the planarity of the molecule. Besides, in crystal 4a,
molecules are linked by pairs of O—HꢀO hydrogen bonds, form-
˚
˚
[
C1—N1 = 1.339(2) A and N1—N2 =1.424(3) A] [47, 48].
2
2
In the crystal structure of 4a, the mean planes of the aromatic
ing centrosymmetric dimmers with a R (8) ring motif (Fig. 2 and
rings of the naphthalene system are oriented at a dihedral angle
Table 2). These dimmers are attached by C—Hꢀπ interactions to
of 1.10(9)°. Thus, they are almost coplanar with an r.m.s deviation
create 3D supramolecular architecture (Fig. 3).
4

S. Zazouli, L. Lâallam and E.M. Ketatni
Journal of Molecular Structure 1239 (2021) 130465
Table 2
Selected hydrogen bonds ( A˚ , °) for 4a and 5a. Cg1, Cg2, and Cg3 represent the centroids of
the C2-C7, C10–C19, and C14–C19 rings, respectively.
D—HꢀA
D—H
HꢀA
DꢀA
D—HꢀA
Symmetry codes
4
5
a
a
O4—H4OꢀO1
C8—H8BꢀCg2
C9—H9AꢀCg1
C13—H13ꢀCg3
C15—H15ꢀCg2
N1—H1ꢀO1
0.84
1.79
2.620(2)
3.513(2)
3.564(2)
3.649(2)
3.483(2)
2.928(2)
3.193(3)
3.136(2)
3.438(2)
3.487(2)
171
-x,-1-y,1-z
0.99
2.66
144
x,-1+y,z
0.99
2.69
148
x,1+y,z
0.95
2.81
147
1-x,1/2+y,1/2-z
1-x,1/2+y,1/2-z
1/2+x, -y+1/2, 1-z
1-x, -y, -z+1
1/2+x, -y+1/2, 1-z
1/2-x, 1/2+y, z
1/2-x,-1/2+y, z
0.95
2.70
141
0.91(2)
0.94(2)
0.95
2.03(2)
2.28(3)
2.44
168(2)
163(2)
130
N2—H2AꢀO1
C7—H7ꢀO1
C8—H8BꢀCg1
C9—H9BꢀCg2
0.99
2.75
127
0.99
2.85
122
Table 3
Some selected (X-ray and DFT) geometric data ( A˚ , °).
Parameters
4a
4b
5a
5b
Bond length ( A˚ )
X-ray
DFT
DFT
X-ray
DFT
DFT
C1—C2
1.474(2)
1.252(2)
1.292(2)
—–
1.480
1.209
1.359
—-
1.480
1.209
1.360
—–
1.489(3)
1.240(2)
1.339(2)
1.424(3)
1.370(2)
1.431(2)
1.433(2)
1.371(2)
1.496(3)
1.495
1.222
1.379
1.413
1.360
1.424
1.420
1.365
1.511
1.495
1.222
1.379
1.414
1.360
1.424
1.420
1.367
1.511
O1—C1
C1—O4/N1
N1—N2
O2—C5
1.360(2)
1.429(2)
1.423(2)
1.370(2)
1.507(2)
1.359
1.425
1.420
1.367
1.519
1.359
1.425
1.420
1.369
1.519
O2—C8
O3—C9
O3—C10
C8—C9
Angles angle (°)
O1—C1—N1/O4
C1—N1—N2
O1—C1—C2
C1—C2—C7
C1—C2—C3
N1/O4—C1—C2
O2—C5—C6
O2—C5—C4
C5—O2—C8
O2—C8—C9
O3—C9—C8
C9—O3—C10
C11—C10—O3
O3—C10—C19
123.5(2)
——
121.8
—–
121.8
—–
121.0(2)
122.1(2)
121.6(2)
124.0(2)
117.7(2)
117.4(2)
124.4(2)
115.7(2)
117.1(2)
108.0(2)
107.8(2)
116.8(2)
124.2(2)
113.9(2)
121.3
119.8
122.8
123.5
117.9
115.9
124.6
115.7
119.1
110.6
108.1
118.9
124.5
114.9
121.3
119.8
122.8
123.5
117.9
115.9
124.7
115.7
119.2
108.0
108.0
118.9
124.6
115.6
120.1(2)
121.1(2)
119.7(2)
116.4(2)
124.8(2)
115.0(2)
118.9(2)
104.5(2)
106.0(2)
117.0(2)
124.9(2)
114.0(2)
125.2
122.5
118.4
113.0
124.4
115.7
119.2
106.1
106.0
118.9
124.3
115.0
125.2
122.5
118.3
113.0
124.4
115.6
119.3
106.2
106.0
118.9
124.4
115.6
2
2
Fig. 2. Inversion dimmers with R (8) ring motifs related by C—Hꢀπ interaction.
In the crystal of compound 5a, the naphthalene system (C10—
C19) is almost planar with an r.m.s. deviation for all non-hydrogen
˚
atoms of 0.029 A (the dihedral angle of the aromatic rings of naph-
Fig. 3. Crystal packing for 4a viewed along the b-axis, showing the O—HꢀO hydrogen bonds and the C—Hꢀπ interaction as dashed lines.
5

S. Zazouli, L. Lâallam and E.M. Ketatni
Journal of Molecular Structure 1239 (2021) 130465
2
2
Fig. 4. (a) Inversion dimmers with R (10) ring motifs viewed along the c-axis. Dotted lines indicate the N—HꢀO and C—HꢀO hydrogen-bonded. (b) A section of a chain
along the b axis formed by weak C—Hꢀπ interaction (shown as green dotted lines).
Fig. 5. Crystal packing of 5a viewed along a-axis. N—HꢀO hydrogen bonds and the C—Hꢀπ interaction are shown as dashed lines orange and green, respectively.
thalene is 2.67(11)°. The phenyl ring is inclined to the naphthalene
mean plane at 78.87(8)°. The O—C—C—O group that links the naph-
thalene and benzohydrazide has a torsion angle of 73.66(17)°. The
hydrazide group O1/C1/N1/N2 is twisted to the attached phenyl
with 15.94(9)°.
matic ring and C10–C19 ring of naphthalene, respectively (Fig. 4b).
A packing diagram is shown in Fig. 5.
3.3. Hirshfeld surface analysis
Molecules of compound 5a exhibit both intermolecular N—HꢀO
and C—HꢀO hydrogen bonds and C—Hꢀπ interactions in the crys-
tal structure (Table 2). On the other hand, the intermolecular N2–
The nature of intermolecular interaction in the title compounds
have been computed by the Crystal Explorer program [40] based
on the results of X-ray studies. The Hirshfeld surface analysis
mapped over dnorm, using standard surface resolution plots as
shown in Fig. 6. The 2D fingerprint maps of C19 H18 N2O3 provide
the individual contribution of the intermolecular interaction in the
asymmetric unit (Fig. 7). The positions of the strong O—HꢀO and
N—HꢀO hydrogen bonds are indicated by the darkest red spots
on the Hirshfeld surface, which has been ascribed to the hydro-
gen bonding interactions formed by a carbonyl oxygen atom and
2
H2BꢀO1 hydrogen bonds form inversion dimers with R (10) ring
2
motifs. Adjacent dimers are linked by N1–H1ꢀO1 and C7–H7ꢀO1
contacts generating corrugated chains of molecules running ap-
proximately parallel to the ab plane (Fig. 4a). Furthermore, in the
5a compound, the molecules are linked by weak interaction of type
C–Hꢀπ, forming supramolecular chains extending along the b-axis
direction, involving the C8–H8B and C9–H9B and the C2–C7 aro-
6

S. Zazouli, L. Lâallam and E.M. Ketatni
Journal of Molecular Structure 1239 (2021) 130465
Fig. 6. Views of Hirshfeld surface for a reference molecule in C19 H18 N2O3 mapped over the dnorm to visualize the intermolecular N–HꢀO (4a) and N–HꢀO and short
interatomic CꢀH/HꢀC contacts (5a) as green dashed lines.
H-hydroxyl (4a) as well as NH and amine group for 5a. The other
red regions indicate contact point with atoms participating in in-
termolecular C—HꢀO and C—Hꢀπ interactions (Table 2).
Waals interactions and hydrogen bonding play dominant role in
stabilizing the structures.
The overall two-dimensional fingerprint plot (Fig. 7a) and those
delineated into HꢀH, HꢀC/CꢀH, HꢀO/OꢀH, and CꢀO/OꢀC for 4a
HꢀN/NꢀH for 5a and CꢀC contacts are illustrated in Fig. 7 b–f, re-
spectively, together with their relative contributions to the Hirsh-
feld surface. The most important interaction is HꢀH contributing
3.4. Theoretical study
3.4.1. Optimized molecular structure
The optimized molecular structure of 4a-b and 5a-b obtained
by using the DFT/B3LYP functional method is presented in Fig. 9.
The selected Geometric parameters from the X-ray analysis are
displayed in Table 3. These geometrical parameters are compared
in the same table with the corresponding theoretical ones deter-
mined. Hence, some small differences were noticed between some
4
4.7% (4a) and 46.1% (5a) to the overall all crystal packing, which
is revealed in Fig. 7b as widely scattered points of high density due
to the large hydrogen content of the molecule with the small split
˚
˚
tips at de ≈ d ≈ 1.20 A (4a) and de ≈ d ≈ 1.25 A (5a). The promi-
i
i
nent features in Fig. 7c reflect the significant CꢀH/HꢀC contacts
evident in the packing, the main contribution with 30.4 % (4a) and
values as C1—O1 bond lengths in the crystal structure that are
1.252(2) A˚ for 4a and 1.240(2) A˚ for 5a, although, in DFT-optimized,
33.8% (5a) of the surface is from CꢀH contacts in C—Hꢀπ interac-
the calculated values are 1.209 and 1.222 A˚ , respectively. Moreover,
tions between the centroids of C2-C7 and C10-C14/C19 rings and
ethoxy H-atoms (H8b and H9b), Table 2, in the crystal (Fig. 8) and
viewed as the distribution of points in the form of characteristic
C1—O4 (4a) and C1—N1 (5a) bonds lengths in the crystal structure
are 1.292(2) A˚ and 1.339(2) A˚ , while in DFT the calculated values
are 1.359 A˚ and 1.379 A˚ for 4a and 5a respectively. Thus, from the
˚
wings with de + d ≈ 2.7 A. The contribution from the OꢀH/HꢀO
theoretical values, most of the optimized bond lengths are in good
agreement with experimental bond lengths however bond angles
are slightly longer and shorter than that of experimental values.
This sensitive gap can be explained by the fact that the theoretical
calculations were performed in the gas phase, whereas the experi-
mental results were purposed for the solid state (crystalline state).
i
contacts (17.3% for 4a and 14.1% for 5a) between the oxygen atoms
inside the surface and the hydrogen atoms outside the surface,
corresponding to O—HꢀO and N—HꢀO interactions, respectively,
is represented by a pair of sharp spikes characteristic of strong
˚
hydrogen-bond interaction, de + d ≈ 1.65 A for 4a and de + d
i
i
˚
1.95 A for 5a (Fig. 7d). A further small contribution from the
≈
other different interatomic contacts to the Hirshfeld surfaces are
3.4.2. DFT calculations
as follows: CꢀO/OꢀC (4.8%, Fig. 7e), CꢀC (2.4%, Fig. 7f), and OꢀO
Frontier molecular orbitals (FMOs) are the most important or-
bitals in molecule, called highest occupied orbital (HOMO) and
lowest unoccupied orbital (LUMO) as well as HOMO-LUMO energy
gap is considered a highly effective parameter for estimating re-
activity in quantum chemistry [49-52]. The molecular structure in
the ground state of the compounds which is refined X-ray data was
(
0.3%) for 4a and NꢀH/HꢀN (3.7%, Fig. 7e), CꢀC (1.4%, Fig. 7f), and
NꢀC/CꢀN (0.8%) for 5a.
The Hirshfeld surface analysis confirms the importance of H
atoms contacts in establishing the packing. The large number of
HꢀH, CꢀH/HꢀC and OꢀH/HꢀO interactions suggest that van der
7

S. Zazouli, L. Lâallam and E.M. Ketatni
Journal of Molecular Structure 1239 (2021) 130465
Fig. 7. The full two-dimensional fingerprint plots and relative contributions of various interactions to the Hirshfeld surface of the title compounds, corresponding to (a) all
interactions, (b) HꢀH, (c) HꢀC/CꢀH, (d) HꢀO/OꢀH, and (e) CꢀO/OꢀC for 4a HꢀN/NꢀH for 5a, and (f) CꢀC.
8

S. Zazouli, L. Lâallam and E.M. Ketatni
Journal of Molecular Structure 1239 (2021) 130465
the whole molecule except for the amine and -CH2-CH2- groups.
Based on the HOMO and LUMO energy, following parameters were
calculated; energy gap (ꢀE), chemical hardness (η) and chemical
softness (ξ) of compounds, chemical potential (μ) and all other pa-
rameters are given in Table 4. The results revealed that compound
4a is moderately soft with band gap energy corresponds to 4.500
eV. This implies that the molecule is more polarized thus exhibits
higher chemical reactivity than the other compounds. On the other
side, the chemical potential of 4a is smaller compared to 4b and
5
a lower than 5b; therefore 4a and 5a behave as an acceptor of
electrons. The chemical hardness for 4a is smaller than those of
b, indicating that the electrons are attracted from compound 4a.
4
Apart from this, the electrophilicity index of the compound is also
calculated and it is one of the most important quantum chemi-
cal parameters for the quantification of the global electrophilic na-
ture of a molecule. The high electrophilicity (2.925 eV) of 4b in-
dicates its act as an electrophile. Considering the dipole moments
(
D) the aforementioned computations showed that compounds 5b
are highly polar in nature and relatively more reactive when com-
pared to other studied compounds.
3
3
.4.3. Molecular Properties
.4.3.7. Mulliken population analysis. The Mulliken charge value
was calculated using B3LYP functional with a 6-311G (d, p) basis
set for the title compound. The distribution of Mulliken atomic
charge is reported in Table 5. The C1, C5, and C10 atoms of all
molecules have positive charges, while the other carbon has neg-
ative charges; the C1 has a high positive charge when attached to
the N and O atoms. Moreover, all the hydrogen atoms have a net
positive charge. O1, O2, and O3 atoms have high negative charge
values which impose positive charges to C1, C5, and C10, respec-
tively. Also, the results illustrate that the C1 atom has a greater
positive value than other atoms in all molecules present in the hy-
drazide or COOH group.
Fig. 8. Shape-index property highlighting C—Hꢀπ stacking interactions as green
lines for (a) 4a and (b) 5a.
fully optimized via density functional theory (DFT) using the stan-
dard B3LYP functional and 6–311G (d, p) basis-set calculations. The
energy levels of the HOMO (highest occupied molecular orbital)
and LUMO (lowest occupied molecular orbital) for 4a-b and 5a-b
were obtained are plotted in Fig. 10. As seen from this Fig., HOMO
of the compounds 4a and 4b is mainly localized on the methoxy-
naphthalene and methoxyphenyl, respectively. While the LUMO is
localized on the benzoic acid. The HOMO of 5a and 5b are concen-
trated on the naphthalene, whereas the LUMO is concentrated over
For 5a-b, Mulliken atomic charge shows the O1 atom exhibit
maximum negative charge values (-0.372e). This result reveals that
there is charge transfer through the N—HꢀO hydrogen bonds. Be-
sides, the H atom attached to N1 and N2 has a higher positive
atomic charge (0.238 and 0.214/0.222, respectively) than the other
hydrogen atoms. Thus, the result obtained by Mulliken charge
analysis is following the molecular electrostatic potential map.
Fig. 9. Optimized structure of compounds 4a-b and 5a-b calculated with the B3LYP/6-311G (d, p).
9

S. Zazouli, L. Lâallam and E.M. Ketatni
Journal of Molecular Structure 1239 (2021) 130465
Fig. 10. Frontier molecular orbitals (FMOs) of 4a-b and 5a-b.
Table 4
HOMO–LUMO energies and values of quantum chemical parameters of 4a-b and 5a-b
calculated by B3LYP/6-311G (d, p)
4a
4b
5a
5b
ET (eV)
-28147.488
-5.840
-1.340
4.500
-23967.480
-6.350
-1.318
5.032
-29111.834
-5.756
-1.115
4.641
-24931.843
-6.261
-1.058
5.203
EHOMO (eV)
ELUMO (eV)
ꢀ
E(LUMO–HOMO) (eV)
Chemical hardness (η)
Chemical Softness (ξ)
Chemical potential (μ)
Electrophilicity (ψ)
Electronegativity (χ)
Dipole moment (D)
2.250
2.516
2.320
2.601
0.222
0.199
0.215
0.192
-3.590
2.861
-3.834
2.925
-3.435
2.537
-3.659
2.571
3.590
3.834
3.435
3.659
2.319
2.503
4.271
4.422
2
η = 1/2[ELUMO-EHOMO], ξ = 1/2η, μ = [1/2(ELUMO+EHOMO)], ψ = μ /2η, χ = -μ
3
.4.3.8. Molecular Electrostatic Potential (MEP). The molecular elec-
311G (d, p) basis set and can be obtained by a frequency job output
file of Gaussian. The complete equations for calculating the mean
dipole moment (1), polarizability (2), and the first hyperpolariz-
ability (3) are as follows:
trostatic potential (MEP) is the plot of electrostatic potential
mapped onto the constant electron density surface, allowing the
prediction of sites and relative reactivity towards electrophilic at-
tack and nucleophilic reactions of molecules [53,54]. The MEP
maps of the synthetic compounds were calculated at DFT/B3LYP/6-
2
2
y
2
z
μ
tot = (μ + μ + μ )1/2
(1)
x
311G (d, p) optimized geometry is computed, contour and surface
α
tot = (αxx + αyy + αzz
)
(2)
map is displayed in Fig. 11. The red and blue-colored regions indi-
cate the negative electrostatic potential (nucleophiles) and positive
electrostatic potential (electrophile), respectively. The green region
shows neutral potential. The MEP map of 4a, 4b, 5a, and 5b is
ꢀ
ꢁ
1
/2
2
2
2
β = (βxxx + βxyy + βxzz ) + (βyyy + βyzz + βyxx ) (βzzz + βzxx + βzyy
)
−
2
−2
−2
in the range -5.273 × 10
V to 5.273 × 10
V, -5.160 × 10
(
3)
−2
−2
−2
V to 5.160 × 10
V, -5.576 × 10
V to 5.576 × 10
V, and -
−2
−2
The values of dipole moment, polarizability and the first hyper-
polarizability for 4a-5a and 4b-5b are reported in Tables SI1 and
SI2, respectively. The polarizabilities and hyperpolarizability are re-
ported in atomic units (a.u), converted into electrostatic units (esu)
5
.612 × 10 V to 5.612 × 10 V, respectively.
For all compounds, the total electron density surface mapped
with electrostatic potential indicates the presence of a high neg-
ative charge on the oxygen O1 atom of the carbonyl group. Al-
though, the positive region of the MEP map is localized over the
hydroxyl and N-H group, indicating that they are susceptible sites
for nucleophilic attack (Fig. 11a). Analyses of the MEP surface of
these compounds represent the availability of electrons for possi-
ble interaction with another group of atoms. The MEP results are
supported by the electrostatic potential contour map showing the
lines isosurface in Fig. 11b.
−
24
−33
(
α: 1a.u = 0.1482 × 10
esu, β: 1a.u. = 8.6393 × 10
esu). The
total molecular dipole moment is found to be 2.453, 2.503, 4.271,
and 4.422 D for 4a, 4b, 5a, and 5b respectively. Besides, the calcu-
lated first order hyperpolarizability is equal to 1.414 10 30, 0.854
−
−
30, 0.727 10
−30
−30
10
, and 0.646 10 esu for 4a, 4b, 5a, and 5b, re-
spectively.
3
.4.3.10. Natural bond orbital (NBO) analysis. The NBO method
gives information about interactions in both filled and virtual
spaces that could enhance the analysis of intra- and intermolec-
ular interactions [55,56]. The NBOs are made up of a combination
3
.4.3.9. Nonlinear Optical Properties (NLO). The polarizability, first
polarizability, and dipole moment are calculated using B3LYP/6-
10

S. Zazouli, L. Lâallam and E.M. Ketatni
Journal of Molecular Structure 1239 (2021) 130465
Fig. 11. (a) The total electron density. (b) The contour map of electrostatic potential mapped with electrostatic potential of 4a-b and 5a-b at an isosurface value of 0.020 a.u.
and an isodensity of 0.0004 a.u.
of natural hybrid orbitals (NHOs) which are further made up of
an optimized linear combination of natural atomic orbitals (NAOs).
These natural localized sets are intermediate between basis atomic
orbitals (AO) and molecular orbitals (MO). These localized describe
electron density and are closely related to the localized orbitals,
while the molecular orbital (MO) are localized over the whole spa-
tial region on atoms in a molecule [57]. On the path to NBOs, an
ordinary MO calculation is done at a high enough level to repro-
duce measured geometry. The natural bond orbital analysis of the
title compound was performed at the B3LYP/6-311G (d, p) level of
the model. Tables SI3-4 regroups the electron in the core, valence,
and Rydberg subshells of the molecule. The percentage contribu-
tion of natural population analysis and natural Lewis structure of
4a and 5a is reported in Fig. 12 and Table SI5.
Natural bond orbital (NBO) analysis has been performed to elu-
Fig. 12. Percentage contribution of natural population analysis and natural Lewis
structure of 4a and 5a.
cidate the intramolecular and the interaction which will weaken
the bond associated with the anti-bonding orbital in a molecule.
For each donor NBO (i) and acceptor NBO (j), the stabilization en-
ergy E(2) [58,59] associated with delocalization i -> j is estimated
as:
11

S. Zazouli, L. Lâallam and E.M. Ketatni
Journal of Molecular Structure 1239 (2021) 130465
Table 5
∗
∗
electron-donating from LP(2)O1→σ (1)O4/N1-C1 and σ (1)C1-C2;
Mulliken charges of 4a and 5a using B3LYP/6-311G
d, p) levels.
∗
∗
LP(2)O2→π C5-C6 and LP(2)O3→π C10-C11 are 24.86/24.93 and
(
−1
1
8.26/18.26; 30.78/31.30 and 29.30/30.40 kcal.mol , respectively
for 4a/5a.
The significant interaction of energy in 4a was the electron
4a
4b
5a
5b
C1
0.425
-0.240
-0.022
0.114
-0.097
0.107
0.198
-0.138
0.113
-0.009
0.111
-0.033
0.125
0.125
-0.023
0.122
0.122
0.204
-0.119
0.106
-0.095
0.094
-0.050
0.081
-0.052
—–
0.425
-0.240
-0.022
0.114
-0.098
0.107
0.198
-0.138
0.114
-0.010
0.111
-0.032
0.124
0.124
-0.024
0.120
0.120
0.178
-0.134
0.108
-0.092
0.096
-0.099
0.093
-0.092
0.096
-0.095
0.101
—–
0.416
-0.196
-0.029
0.113
-0.094
0.111
0.193
-0.138
0.107
-0.050
0.095
-0.028
0.112
0.125
-0.019
0.111
0.123
0.207
-0.121
0.100
-0.095
0.092
-0.051
0.080
-0.051
—–
0.416
-0.197
-0.028
0.112
-0.094
0.110
0.194
-0.139
0.106
-0.050
0.095
-0.027
0.112
0.124
-0.02
0.118
0.121
0.178
-0.095
0.104
-0.092
0.096
-0.100
0.092
-0.092
0.094
-0.136
0.103
—–
∗
C2
coupling between LP(2)O4 to π C1-O1 that stabilizes at 55.37
C3
kcal/mol. While the intermolecular charge transfer from 5a due to
H3
∗
−1
LP(1)N1 to π C1-O1 leading to stabilization of 36.05 kcal.mol
.
C4
∗
Additionally, the highest stabilization energy-containing π C2-
H4
∗
∗
∗
∗
∗
C5
C7→ π C1-O1, π C5-C6→ π C2-C7 and π C3-C4, and π C10-
C6
∗
C11→ π C12-C13 interactions lead to intermolecular charge trans-
H6
fer process in the studied molecules 4a and 5a.
C7
H7
C8
3.4.3.11. Interaction energy calculations. The intermolecular interac-
tion energies between molecules in crystal 4a and 5a computed
using a B3LYP/6–31G (d, p) energy model available in Crystal Ex-
plorer 17.5 [40], where a cluster of molecules was generated within
H8A
H8B
C9
H9A
H9B
C10
C11
H11
C12
H12
C13
H13
C14
H14
C15
H15
C16
H16
C17
H17
C18
H18
C19
O1
˚
a radius of 3.8 A by default. The total intermolecular energy (Etot) is
the sum of electrostatic (Eele), polarization (Epol), dispersion (Edis),
and exchange-repulsion (Erep) energies. The energy frameworks,
which provide a view of the supramolecular architecture of crys-
tals, are represented by cylinders joining the centroids of molecu-
lar pairs using red, green and, blue colour codes for the Eele, Edis,
and ET energy components, respectively, with a cut-off value of 5
−1
kJ.mol
and a scale factor of 60 to all energy components (Fig.
SI15a-c and SI16a-c). The benchmarked energies Eele, Epol, Edis, and
Erep were scaled as 1.057, 0.740, 0.871, and 0.618, respectively [60].
An analysis of the resultant energy frameworks reveals the crystal
of 4a and 5a is stabilized by electrostatic and dispersive forces. The
Edis energy term also makes the major contribution to the energies
-0.070
0.084
-0.083
0.093
-0.094
0.093
-0.011
0.091
-0.113
-0.340
-0.357
-0.373
-0.342
—–
-0.071
0.083
-0.083
0.093
-0.094
0.093
-0.010
0.098
-0.118
-0.372
-0.347
-0.361
—–
—–
—–
—–
—–
—–
—–
of stabilization of -214.1 kJ.mol 1 for 4a and –222.0 kJ.mol
−
−1
for
—–
—–
—–
—–
5a, while the electrostatic energy of all pairwise interactions sums
to -42.5 and -109.1 kJ.mol 1 for 4a and 5a, respectively. The to-
−
—–
—–
-0.341
-0.357
-0.367
-0.342
—–
-0.372
-0.346
-0.355
—–
tal interaction energy that resulted from four main components is
159.1 kJ.mol 1 for 4a and -217.7 kJ.mol
O2
−
−1
-
for 5a (Fig. SI15d and
O3
SI16d).
O4
N1
-0.347
0.238
-0.352
0.214
0.222
-0.347
0.237
-0.352
0.214
0.222
H1N
N2
—–
—–
4. Conclusion
—–
—–
H2A
H2B
—–
—–
We have reported in this work the synthesis of new benzohy-
—–
—–
drazide/benzoic acid derivatives by simple and convenient method-
ology. The structural characterization and NMR analysis were also
discussed. X-ray crystallographic studies for 4a and 5a display in-
termolecular O—HꢀO (4a), N—HꢀO, and C—HꢀO (5a) hydrogen
bonding and C—Hꢀπ interactions, forming layers in the crystal
lattice. The results of Hirshfeld surface analysis indicate that the
major interactions were found for HꢀH interaction with contribu-
tions of 44.7 and 46.1% of the total HS area in 4a and 5a prod-
ucts, respectively. Frontier molecular orbital analysis and molec-
ular electrostatic potential maps of 4a, 4b, 5a, and 5b products
have been studied using DFT calculations. The molecular electro-
static potential analysis gives information about intermolecular in-
teraction regions. The results indicate that compound 4a, with a
smaller LUMO-HOMO gap, more reactive than other compounds.
The molecular electrostatic potential of the studied compounds
showed suitable regions to attack for nucleophilic and nucleophilic
substances. The stability and intermolecular interactions have been
interpreted by NBO analysis.
qi: donor orbital occupancy,
Ei, Ej diagonal elements,
2
E(2) = ꢀEij = qi
F(i, j)
Ej −Ei
Fij the off diagonal NBO Fock matrix element.
The larger stabilization energy E(2) value indicates more inten-
sive interaction between the electron donors and acceptors. NBO
analysis has been performed on 4a and 5a at B3LYP/6-311G (d,
p) method and the results are summarized in Tables SI6 and SI7.
∗
These results indicate several n, π, and π bonds at donor levels
∗
∗
and σ , π, and π orbitals at acceptor levels.
For both compound 4a/5a, the interactions πC2-C7 to π C3-
∗
∗
∗
∗
C4 and π C5-C6; πC3-C4 to π C2-C7 and π C5-C6; πC5-C6 to
∗
∗
π C2-C7 and π C3-C4 were observed in the C2-C7 ring contain-
ing stabilization energy of 22.23/20.86, 16.30/16.67, 16.87/17.31,
4.35/23.53 and 24.47/23.32, 14.69/14.80 kcal.mol 1, respectively
−
2
(
Tables SI6 and SI7). Similarly, in the C10-C19 naphthalene ring, the
∗
∗
interactions πC10-C11 to π C12-C13 and π C14-C19; πC12-C13
Supplementary material
∗
∗
∗
∗
∗
to π C10-C11 and π C14-C19; πC14-C19 to π C10-C11, π C12-
These data include NMR spectra for 4a-b and 5a-b. CCDC
2061733 and 2061734 contain the supplementary crystallographic
data for compound 4a and 5a, respectively. These data can be ob-
tained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or
by emailing data_request@ccdc.cam. ac.uk, or by contacting the
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336033.
∗
∗
∗
C13, π C15-C16, π C17-C18; πC15-C16 to π C14-C19 and π C17-
∗
∗
C18 and πC17-C18 to π C14-C19 and π C15-C16 were found to
be 18.63/18.97, 13.13/13.15; 14.74/15.01, 16.77/17.15; 19.69/20.07,
1
4.75/15.03, 16.25/16.09, 17.90/17.68; 17.27/17.11, 17.74/17.29 and
−
1
6.30/16.21 and 18.66/18.29 kcal.mol 1, respectively. The interac-
tion energy related to the resonance in both molecules is the
12

S. Zazouli, L. Lâallam and E.M. Ketatni
Journal of Molecular Structure 1239 (2021) 130465
Declaration of Competing Interest
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