Synthesis, spectroscopic characterization (FT-IR, NMR) and DFT computational studies of new isoxazoline derived from acridone

Article abstract of DOI:10.1016/j.molstruc.2021.129921

In this study, a new isoxazoline derived from acridone, 10‐{[3‐(4‐chlorophenyl)‐4,5‐dihydro‐1,2‐oxazol‐5 yl]methyl} acridone (3) was successfully synthesized and characterized by FT-IR, ¹H NMR, ¹³C NMR and HRMS. The preparation of compound (3) was achieved by 1,3-dipolar cycloaddition reaction between 4?chloro-N-hydroxybenzimidoyl chloride and 10-allylacridone using environment friendly methods. In an effort to complete the chemical structure description of the synthetized compound, Density Functional Theory (DFT) was applied using Gaussian09 and Gaussian view5 programs. The theoretical calculations were used as a compliment to the experimental studies. The computing of geometric parameters, optimization energies, frontier molecular orbital energies, Molecular surface electrostatic potential (MESP) and Mulliken charges were calculated using DFT/B3LYP method with 6–31G(d,p) as basis set. The Infrared vibrational frequencies and ¹H and ¹³C NMR chemical shifts were also calculated and their scaled values are in agreement with the experimental results.

Full text of DOI:10.1016/j.molstruc.2021.129921

Journal of Molecular Structure 1231 (2021) 129921
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Synthesis, spectroscopic characterization (FT-IR, NMR) and DFT
computational studies of new isoxazoline derived from acridone
a,∗
a
b
a
Mohammed Aarjane , Siham Slassi , Adib Ghaleb , Amina Amine
a
Laboratory of Chemistry/Biology Applied to the Environment, Faculty of Science, University Moulay Ismail, BP 11201 Zitoune, Meknes, Morocco
Laboratory of Analytical and Molecular Chemistry, Multidisciplinary Faculty of Safi, Cadi Ayyad University, Safi, Morocco
b
a r t i c l e i n f o
a b s t r a c t
Article history:
In this study, a new isoxazoline derived from acridone, 10-{[3-(4-chlorophenyl)-4,5-dihydro-1,2-oxazol-5
yl]methyl} acridone (3) was successfully synthesized and characterized by FT-IR, 1H NMR, 13 C NMR and
Received 11 September 2020
Revised 18 December 2020
Accepted 8 January 2021
Available online 11 January 2021
HRMS. The preparation of compound (3) was achieved by 1,3-dipolar cycloaddition reaction between 4–
chloro-N-hydroxybenzimidoyl chloride and 10-allylacridone using environment friendly methods. In an
effort to complete the chemical structure description of the synthetized compound, Density Functional
Theory (DFT) was applied using Gaussian09 and Gaussian view5 programs. The theoretical calculations
were used as a compliment to the experimental studies. The computing of geometric parameters, op-
timization energies, frontier molecular orbital energies, Molecular surface electrostatic potential (MESP)
and Mulliken charges were calculated using DFT/B3LYP method with 6–31G(d,p) as basis set. The Infrared
vibrational frequencies and 1H and 13 C NMR chemical shifts were also calculated and their scaled values
are in agreement with the experimental results.
Keywords:
Acridone
Isoxazoline
NMR
FT-IR
MESP
Mulliken charge
©
2021 Elsevier B.V. All rights reserved.
1
. Introduction
these structures, generally allow them easy intercalation between
the adjacent base pairs of the double helix of DNA [8]. Literature
survey revealed that acridone ring systems are attractive candi-
dates in medicinal chemistry as they constitute the building blocks
of a wide range of many compounds possessing an interesting bio-
logical properties such as being employed as antimicrobial [9–11],
anticancer [12,13], antiviral [14,15] and antimalarial agents [16,17].
In addition, acridone and its derivatives are an interesting tools for
selective recognition of metals and pollutants in ecological and bi-
ological areas [18].
Oxygen-containing heterocyclic compounds have widely stud-
ied due to their remarkable pharmacological properties [1]. Among
these compounds, the isoxazoline ring is considered as a precious
molecular scaffold in the industrial and medicinal fields. Some
isoxazoline derivatives are an essential motifs in several natural
and synthetic compounds that exhibit an interesting pharmacolog-
ical properties such as anticancer [2], antimicrobial [3] and anti-
tuberculosis [4]. The preparation of isoxazoline ring is mostly ob-
tained by cycloaddition reaction between alkene and nitrile oxide.
The dipole intermediate is generally generated in situ from the cor-
responding hydroximoyl chloride or primary nitro compound [5]. A
number of 1,3-dipolar cycloaddition reaction between alkene and
nitrile oxide has been successfully applied to N- and O-alkenyl
derivatives leading to the synthesis of novel compounds contain-
ing isoxazoline ring [5–7].
The aim of this work is to study the chemical structure descrip-
tion of novel acridone containing isoxazoline nucleus, in continu-
ation of our previous studies on acridone derivatives [19,20]. We
focused our attention toward the preparation of novel acridone
based on isoxazoline using environment friendly methods. In
this work, we synthesized 10-{[3-(4-chlorophenyl)-4,5-dihydro-1,2-
oxazol-5 yl]methyl} acridone by cycloaddition reaction between
4–chloro-N-hydroxybenzimidoyl chloride and 10-allylacridone. The
synthesized compound was characterized using different spectro-
scopic methods (IR, 13C NMR and 1H NMR). In order to give a
complete description of the molecule geometry, theoretical inves-
tigations were applied using DFT/B3LYP method with 6–31G(d,p)
as basis set to complete the experimental study relying on com-
puting geometric parameters, optimization energy, vibrational fre-
quencies, NMR, the frontier molecular orbital energies, Molecular
surface electrostatic potential (MESP) and Mulliken charges.
On the other hand, acridone is a linear tricyclic ring contain-
ing nitrogen atom and two benzene rings attached symmetrically
at right hand side and left hand side keeping the pyridine nucleus
in the middle. The flatness of the polycyclic aromatic nucleus in
∗
Corresponding author.
E-mail address: aarjane.mohammed@gmail.com (M. Aarjane).
https://doi.org/10.1016/j.molstruc.2021.129921
0
022-2860/© 2021 Elsevier B.V. All rights reserved.

M. Aarjane, S. Slassi, A. Ghaleb et al.
Journal of Molecular Structure 1231 (2021) 129921
2. Experimental
7.63 – 7.50 (m, 4H, Ar–H), 7.85–7.53 (d, J = 8.2 Hz, 2H, Ar–
H), 7.49 – 7.40 (m, 2H, Ar–H), 7.39–7.31(m, 2H, Ar–H), 5.42–
2
.1. Synthesis
5.31 (m, 1H, CH), 4.72 (dd, J = 15.4, 7.6 Hz, 1H, CH ), 4.54 (dd,
2
J = 16.3, 4.5 Hz, 1H, CH ), 3.56 (dd, J = 16.7, 7.1 Hz, 1H, CH ),
2
2
13
2.1.1. 10-allylacridin-9(10H)-one (2)
3.27 (dd, J = 16.7, 7.1 Hz, 1H, CH ). C NMR (75 MHz, CDCl ,
2
3
To a mixture of acridone (0.5 g, 2.5 mmol), potassium car-
25 °C, TMS): 177.79, 156.09, 143.07, 142.08, 140.29, 136.64, 135.47,
bonate (0.5 g, 3.6 mmol) and Tetra-n-butylammonium bromide
TBAB) (0.5 g, 2 mmol) in DMF (5 ml), allyl bromide (0.42 g,
.6 mmol) was added and the mixture was stirred at room tem-
133.89, 131.77, 131.55, 130.45, 129.16, 128.12, 128.04, 127.40, 127.31,
(
122.43, 121.53, 114.81, 114.70, 79.10, 48.47, 38.24. MS (ESI) for
+
3
C24H17 ClN O4 [M + H] , calcd: 389.1019, found: 389.1018.
2
perature for 6 h. After that, it was poured into water and the
white yellow formed precipitate was recrystallized from methanol-
DMF.
2
.2. Computational details
The DFT method and hybrid functional (B3LYP) levels with
White crystals; yield: 70%, mp = 133 °C. IR (KBr): 3110, 3065,
−
. H NMR (300 MHz, DMSO–d , 25 °C,
6
1
1
double-zeta basis set 6–31G(d,p) were used to optimize the ge-
ometry of compound (3) and harmonic frequencies, Molecular
orbital frontiers and Mulliken Atomic Charges were determined.
The molecular electronic density and local reactivity indices were
calculated to determine the possibility of molecular interactions
with other species around the space by sharing electronic den-
sity. The GIAO approach within DFT method is the most reli-
able approach for calculating NMR spectra. The NMR chemical
shifts were computed for the compound (3) at GIAO-B3LYP/6–
1
637, 1598, 1502, 1269 cm
TMS): 8.34 (dd, J = 8.1, 1.7 Hz, 2H, Ar–H), 7.85–7.81 (m, 4H, Ar–H),
.38–7.32 (m, 2H, Ar–H), 5.96–5.83 (m, 1H, Ar–H), 5.21–5.19 (dd,
J = 7.6, 1.6 Hz, 1H, CH ), 5.23–5.24 (m, 1H, CH ), 5.09–5.06 (m, 2H,
7
2
2
13
CH ). C NMR (75 MHz, DMSO–d 25 °C, TMS) δ 177.09, 141.70,
2
6,
1
34.76, 134.42, 127.18, 127.00, 122.37, 122.20, 117.44, 116.57, 116.57,
4
5.91.
2
.1.2. 10-{[3-(4-Chlorophenyl)-4,5-dihydro-1,2-oxazol-5 yl]methyl}
31G(d,p) level of theory in the chloroform (using PCM model).The
acridone (3)
A mixture of 4–chloro-N-hydroxybenzimidoyl chloride (0.25 g,
.6 mmol) and Triethylamine (TEA, Et N) (0.16 g, 1.6 mmol) were
calculated harmonic vibrational frequencies were scaled by 0.960
−1 −1
above 3000 cm ) and 0.961(below 3000 cm ) for B3LYP/6–
(
1
3
311G(d,p) level [21–23]. The entire calculations were realized by
using GaussView 5.0 program [24] and Gaussian 09 W program
packages on a computing system [25].
suspended in 6 mL of chloroform in a glass vial equipped with
a small magnetic stirring bar. To this, 10-allylacridone (0.29 g,
1.75 mmol) was added and the vial was tightly sealed. The mixture
was then irradiated for 25 min at a fixed temperature (40−70 °C).
Microwave irradiation power was set at 200 W maximum. Af-
ter the completion of the reaction, water (30 ml) was added and
the mixture was extracted with chloroform, the organic layer was
evaporated in high vacuum, and the obtained product was purified
by recrystallization in methanol/hexane.
3. Results and discussions
3.1. Synthesis
The chemical synthesis of 10-{[3-(4-chlorophenyl)-4,5-dihydro-
1,2-oxazol-5 yl]methyl} acridone (3) is outlined in Scheme 1. Fol-
lowing a published procedure [26], acridone (1) was prepared by
condensation reaction of aniline with 2-bromobenzoic acid in the
presence of copper and potassium carbonate in DMF, followed by
Yellow solid; yield: 77%, mp = 159 °C. IR (KBr): 3011, 2985,
−
. H NMR (300 MHz, CDCl , 25 °C, TMS):
3
1
1
1
639, 1604, 1590 cm
8
8.60 (dd, J = 8.1, 1.7 Hz, 2H, Ar–H), 7.74–7.69 (m, 2H, Ar–H),
Scheme 1. Synthesis route of compound 3.
2

M. Aarjane, S. Slassi, A. Ghaleb et al.
Journal of Molecular Structure 1231 (2021) 129921
allylacridone (2) was prone to be participated in 1,3-dipolar cy-
cloaddition reaction with 4–chloro-N-hydroxybenzimidoyl chloride
in the presence of triethylamine in chloroform, the novel isoxazo-
line (3) was obtained with good yield (77%) (Scheme 1).
3
.2. Molecular geometry of compound (3)
The Density Functional Theory (DFT) is a computational quan-
tum modeling method that gives very precise results. The most
stable optimized molecular structure of 10-{[3-(4-chlorophenyl)-
4
,5-dihydro-1,2-oxazol-5 yl]methyl} acridone (3) was obtained by
the programs Gaussview 05 and Gaussian 09 using B3LYP level and
–31G(d,p) basis set, the most stable geometry of compound (3) is
6
presented in the Fig. 1.
The optimized geometry of compound (3) shows that the
acridone nucleus is not completely planar; but it is bend of ap-
proximately 2.3°, relative to the axis that passes through the ni-
trogen of the amino and the keto groups. Moreover, the struc-
ture of compound (3) have a planar orientation for isoxazoline ring
with the phenyl group, it is quite evident from the obtained dihe-
dral angle 179° between the atoms that connecting the two rings
C37–C35–N33–C32 (Table 1). Furthermore, the O34–C27 bond length
Fig. 1. Optimized geometry of 10-{[3-(4-chlorophenyl)-4,5-dihydro-1,2-oxazol-5
yl]methyl} acridone (3).
an acid catalyzed ring closure reaction of N-phenylanthranilic acid
using sulfuric acid. The N-allyl acridone was obtained in high yield
by N-alkylation of acridone ring with the allyl bromide in the
presence of catalytic amounts of TBAB in DMF. The resulting 10-
˚
found to have a length of about 1.50 A, reflecting purely a σ-
bond character. Similarly, the O34–N32 bond of isoxazoline ring also
Table 1
Geometrical parameters of 10-{[3-(4-chlorophenyl)-4,5-dihydro-1,2-oxazol-5 yl]methyl} acridone (3).
Bond length
B3LYP/631-G (d.p)
Angle Bond
B3LYP/631-G(d.p)
Dihedral angle
B3LYP/6–31-G (d.p)
C2–C1
1.39
1.41
1.42
1.41
1.39
1.47
1.47
1.42
1.42
1.08
1.39
1.40
1.39
1.09
1.08
1.08
1.09
1.08
1.08
1.26
1.41
1.47
1.09
1.09
1.08
1.54
1.54
1.09
1.10
1.10
2.37
1.30
1.44
1.47
1.41
1.41
1.40
1.08
1.39
1.08
1.39
1.08
1.08
1.82
C1–C3–C2-
120.25
118.61
119.83
121.13
121.30
115.99
121.10
118.16
121.04
120.65
121.03
118.85
118.83
119.06
116.93
118.98
120.43
121.89
122.21
120.31
118.60
108.96
107.62
120.65
115.47
114.18
110.78
112.23
112.22
72.64
C2-C4-C3-C2
2.20
C3–C2
C2–C4–C3
C3-C5-C4-C3
-2.22
C4–C3
C3–C5–C4
C4-C6-C5-C4
0.53
C5–C4
C4–C6–C5
C3-C7-C4-C3
176.87
-2.68
C6–C5
C3–C7–C4
C4-C8-C7-C4
C7–C4
C4–C8–C7
C7-C9-C8-C7
4.15
C8–C7
C7–C9–C8
C8-C10-C9-C8
179.96
178.29
-0.47
C9–C8
C8–C10–C9
C9-H11-C10-C9
C9-C12-C10-C9
C10-C13-C12-C12
C12-C14-C13-C12
C2-H15-C1-C2
C10–C9
H11–C10
C12–C10
C13–C12
C14–C13
H15–C1
H16–C2
H17–C5
H18–C12
H19–C13
H20–C14
O21–C7
N22–C9
C23–N22
H24–C23
H25–C23
H26–C6
C27–C23
C28–C27
H29–C27
H30–C28
H31–C28
N32–C28
C33–N32
O34–N32
C35–C33
C36–C35
C37–C35
C38–C36
H39–C36
C40–C37
H41–C37
C42–C38
H43–C38
H44–C40
Cl45–C42
C9–H11–C10
C9–C12–C10
C10–C13–C12
C12–C14–C13
C2–H15–C1
C1–H16–C2
C4–H17–C5
C10–H18–C12
C12–H19–C13
C13–H20–C14
C4–O21–C7
C8–N22–C9
C9–C23–N22
N22–H24–C23
N22–H25–C23
C5–H26–C6
C22–C27–C23
C23–C28–C27
C23–H29–C27
C27–H30–C28
C27–H31–C28
C27–N32–C28
C28–C33–N32
C28–O34–N32
N32–C35–C33
C33–C36–C35
C33–C37–C35
C35–C38–C36
C35–H39–C36
C35–C40–C37
C35–H41–C37
C36–C42–C38
C36–H43–C38
C37–H44–C40
C38–Cl45–C42
0.11
0.22
-179.39
175.07
-179.69
179.68
179.95
-179.99
178.44
0.25
C1-H16-C2-C1
C4-H17-C5-C4
C10-H18-C12-C10
C12-H19-C13-C12
C13-H20-C14-C13
C4-O21-C7-C4
C8-N22-C9-C8
C9-C23-N22-C9
N22-H24-C23-N22
N22-H25-C23-N22
C5-H26-C6-C5
167.90
-149.41
-34.34
-179.98
87.70
C22-C27-C23-C22
C23-C28-C27-C23
C23-H29-C27-C23
C27-H30-C28-C27
C27-H31-C28-C27
C27-N32-C28-C27
C28-C33-N32-C28
C28-O34-N32-C28
N32-C35-C33-N32
C33-C36-C35-C33
C33-C37-C35-C33
C35-C38-C36-C35
C35-H39-C36-C35
C35-C40-C37-C35
C35-H41-C37-C35
C36-C42-C38-C36
C36-H43-C38-C36
C37-C35-N33-C32
C38-Cl45-C42-C38
-161.57
-33.36
117.97
-3.10
-120.52
-177.08
1.80
35.82
73.80
-178.86
179.08
-0.97
121.22
120.67
120.58
120.92
120.34
120.76
119.10
118.79
120.72
120.67
119.10
-179.98
0.04
179.99
-0.08
-0.03
179.99
179.08
-179.96
3

M. Aarjane, S. Slassi, A. Ghaleb et al.
Journal of Molecular Structure 1231 (2021) 129921
Fig. 2. Graphical representation of the experimental (blue line) and simulated (red line) IR spectrum of compound (3).
˚
Table 2
found to have a σ-bond character with a length of about 1.45 A
Table 1).
Comparison of the experimental and theoretical FT-IR spectra analysis of the (3)
(
compound.
Experimental
FT-IR (cm-1)
Theoretical
3
.3. FT-IR spectral analysis
FT-IR (cm-1)
Assignmenta
3
2
005 (m)
989 (m)
3089
3039
2972
2901
1648
1600
1556
1548
1540
ν(C-H)(aromatic ring)
ν(C-H)(aromatic ring)
The experimental and theoretical FT-IR spectrum of 10-{[3-(4-
chlorophenyl)-4,5-dihydro-1,2-oxazol-5 yl]methyl} acridone (3) are
given in Fig. 2, The theoretical spectrum was obtained with the
DFT model, B3LYP/6–31 G (d,p). The calculated and experimental
vibrational assignments frequencies for various functional groups
are represented in Table 2.
2902 (w)
ν
ν
as(C-H2)+ ν(C-H)
2
1
1
1
890 (w)
631 (m)
604 (s)
596 (s)
s(C-H2)
ν(C=O)
ν(C=N)
ν(C=C)+α(C-H2)
ν(C=C)+γ (C-H)
(
aromatic ring)
1
492 (s)
α(C-H2)+α(C-H)+ ν(C=C)
ν(C=C)+γ (C-H2)
1
532
1524
516
1452
3
.4. Aromatic and aliphatic C–H vibrations
α(C-H )+γ (C-H)
2
(aromatic ring)
1
γ (C-H)(aromatic ring)
1
464 (m)
ν(C=C)+γ (C-H)(aromatic ring)
γ (C-H)(aromatic ring)
The aromatic C–H mode of vibration mostly occurs between
1
1
1
436
428
420
−
3
100 - 3000 cm 1 [27]. In the experimental spectra of 10-{[3-
ν(C-O)+(C=C)+γ (C-H)(aromatic ring)
ν(C=C)+γ (C-H)(aromatic ring)
δ(C-H2)+
(
4-chlorophenyl)-4,5-dihydro-1,2-oxazol-5 yl]methyl} acridone (3),
−1
a bands in the region 3005–2989 cm
are due to the aro-
1396
δ(C-H)+ν(C=C)+β(C-H)(aromatic)
γ (C-H2)+α(C-H)(aro. ring)+ν(C=C)+γ
matic C–H stretching frequencies. These frequency values exhibit
1
388
good agreement with the theoretical computed ones that detected
(
N-C)+β (O-C)
at 3089–3039 cm 1. The aliphatic C–H vibration generally oc-
−
1
377 (m)
1356
1308
α(C-H)(aromatic ring))+ν(C=C)+ ω(C-H2)
−1
curs between 3000 and 2850 cm
[28]. In the theoretical spec-
γ (C-H )+α(C-H)
+ν(C=C)+γ (N-
2
(aro. ring)
tra, the C–H stretching vibrations are resulted as weak bands at
O)
δ(C-H2)+ν(C=C)+β(C-H)
ν(C-N)+β(C-
−
1300
1292
2
2
972–2901 cm 1. In the experiment, these bands were observed at
(aromatic ring)
1
1
265 (m)
180 (s)
902 - 2890 cm 1. Hence, the experimental results are in harmony
−
H)(aromatic ring)+ν(C=C+ω(C-H2)
ν(C-O)+(C=C)+γ (C-H)(aromatic ring)
δ(C-H2)+α(C-H)(aromatic ring)+ν(C-N)
+α(C-H)(aromatic ring)+ δ(C-H2)
ν(N-O)+α(C-H)(aromatic ring)+ω(C-H2)
β(C-H)(aromatic ring)+δ(C-H)+γ (C-H2)
γ (N-O)+β(C-H)
with the theoretical ones (Fig. 2).
1116
1
1
108
084
3
.5. C=O, C=N and C=C vibrations
1
045 (m)
1044
84
8
−
1
836 (s)
56 (s)
876
860
852
The C=O stretching appears in the range 1850–1600 cm
(aromatic ring)
−
1
β(C-H)(aromatic ring)+β(C-C)
[
29,30]. For compound (3), the band spotted at 1631 cm
in FT-
7
ν (C-Cl)+θ(C-H)(aromatic ring)+β(C-C)
θ(C-H)(aromatic ring)+ β(C-C)
IR spectra, while the corresponding DFT wavenumber is shown
7
88
at 1648 cm 1 are assigned to the C=O stretching mode. The
−
672 (m)
512 (m)
780
500
γ (Cl-C)+β (N-C)+β (C-C)
−
1
C=N stretching arises in the range 1650–1550 cm
[31]. In this
study, C=N stretching band in isoxazoline ring was appeared at
β(C-C)+ β(C-Cl)
a
Vibrational modes: ν; stretching (s; symmetric. as; asymmetric). γ ; rocking. α;
scissoring. ω; wagging. δ; twisting. β; in- plane bending. θ; ring breathing.
−1
1
604 cm . This frequency value shows good conformity with the
theoretically computed one, observed at 1600 cm 1. The charac-
−
teristic aromatic C=C stretching vibrations occurs in the 1610–
−
1
1450 cm
[32]. In the theoretical spectra results, the obtained
−
1
bands at 1556, 1548, 1532, 1452 and 1420 cm were assigned to
3.6. C–N vibration
C=C vibrations and the experimental frequencies of C=C stretching
−1
are observed at 1596, 1492 and 1464 cm
in the FT-IR spectrum
The identification of C–N stretching vibrations is one of the
more complicated ones, meanwhile the mixing of several bands are
of compound (3).
4

M. Aarjane, S. Slassi, A. Ghaleb et al.
Journal of Molecular Structure 1231 (2021) 129921
Table 3
Theoretical and experimental 1H and 13 C chemical shifts of compound (3).
B3LYP/631G(d)
(Chloroform)
Experimental
(Chloroform)
B3LYP/631G(d)
(Chloroform)
Experimental
(Chloroform)
Proton label
Carbon label
H20
H17
H41
H39
H18
H15
H44
H43
H16
H11
H26
H19
H29
H24
H25
H30
H31
8.61
8.53
8.21
8.16
7.60
7.57
7.27
7.23
7.17
7.15
7.13
7.01
5.36
4.52
4.16
3.99
3.45
8.60 (d)
C7
182.51
164.81
153.49
144.03
143.02
134.93
134.40
131.19
130.48
130.28
130.17
129.98
129.96
129.85
127.60
127.17
123.67
123.17
119.69
116.29
81.66
177.79
156.09
143.07
142.08
140.29
136.64
135.47
133.89
131.77
131.55
130.45
129.16
128.12
128.04
127.40
127.31
122.43
121.53
114.81
114.70
79.10
8.57 (d)
C33
C42
C3
7.74–7.69 (m)
7.63–7.60 (m)
7.58–7.53 (m)
7.49–7.40 (m)
7.39–7.31 (m)
C9
C1
C12
C14
C35
C40
C36
C5
5.40–5.35 (m)
4.72 (dd)
C38
C37
C8
4.54 (dd)
3.56 (dd)
C4
3.27 (dd)
C6
C13
C2
C10
C27
C23
C28
60.36
48.47
48.51
38.24
possible in the region [33]. Generally the ring C–N stretching vibra-
3.7. C–Cl vibration
The C–Cl vibrations are found mostly between 900 and
−
1
tion occurs in the region 1380–1220 cm [34]. For the theoretical
−1
results of the compound (3), the value at 1292 cm
is assigned
500 cm 1 [29]. In the experimental spectra of 10-{[3-(4-
−
to the ring C–N stretching mode of vibration, and the FT-IR band
observed at 1265 cm 1 in the spectra which showed full agree-
ment between the theoretical and the experimental results for the
corresponding mode of vibration.
−
chlorophenyl)-4,5-dihydro-1,2-oxazol-5 yl]methyl} acridone (3), the
stretching bands of C–Cl appear at 756 cm 1. While theoretically,
these modes are predicted at 852 cm 1. The bending in plane
−
−
Fig. 3. 1H NMR of compound 3 (CDCl3).
5

M. Aarjane, S. Slassi, A. Ghaleb et al.
Journal of Molecular Structure 1231 (2021) 129921
Fig. 4. Linear regression analyses of calculated 1H and 13 C chemical shifts vs experimental chemical shifts of compound 3.
mode is detected at 500 cm 1. These frequency values exhibit good
−
tained by DFT method that showed good agreement with the ex-
perimental values. The chemical displacement of the proton (CH29)
of isoxazoline ring is in the order of 5.4 ppm, whereas in the case
of 3,4-disubstituted isoxazoline is expected to be higher value due
to the presence of oxygen-attracting effect. These results obtained
from both theoretical and experimental studies confirm the regios-
electivity of the cycloaddition reaction.
Concerning 13C NMR, the calculated chemical shift values by the
DFT method showed an excellent agreement with the experimental
values. The theoretical spectrum of the aromatic carbons are ob-
served from 182 to 116 ppm, while in the experimental spectrum
are detected between 177 and 114 ppm.
agreement with the theoretically computed ones that detected at
5
12 cm 1 (Table 2).
−
3
.8. NMR spectral analysis
The NMR spectroscopy is the most interesting technique for
the structural conformational analysis for the organic compounds
[
35]. In this study, 10-{[3-(4-chlorophenyl)-4,5-dihydro-1,2-oxazol-
yl]methyl} acridone (3) was characterized by 1H and 13C NMR
5
spectroscopy. Both spectra of compound (3) were recorded in chlo-
roform. The GIAO 1H and 13C NMR chemical shift values, with a
respect to TMS, were obtained by using the B3LYP /6– 31G(d,p)
The chemical displacements for the CH carbon of the isoxazo-
line nucleus are observed at 79 ppm, find their explanation in the
oxygen attractor effect of the isoxazolic nucleus. Moreover, the sig-
nals at 48 ppm and 38 ppm are corresponding to the CH2 groups,
while the calculated values, obtained in the interval 81 to 48 ppm
are corresponding to C23, C27 and C28. These results are in good
agreement with the experimental ones. We also noticed the pres-
ence of tow signals at 156 ppm and 177 ppm, which indicate that
they are corresponding to the carbon C=N of the isoxazoline ring
and the carbonyl (C=O) of the acridone nucleus, while the calcu-
lated values are observed at 164 ppm and 182 ppm, respectively.
The correlations coefficient values between the experimental
and theoretical studies for both 1H and 13C NMR were found to
be R2 = 0.97. The linear regressions between the experimental and
model. The theoretical and experimental chemical 1H NMR and 13
C
NMR shifts obtained are given in Table 3.
The experimental 1H NMR spectrum of compound (3) (Fig. 3),
showed aromatic protons between 8.60–7.31 ppm, they were com-
puted at the interval 8.61–7.01 ppm in chloroform. We also no-
tice the presence of two signals as double doublet between
4
.72–4.54 ppm attributable to the two protons of the methylene
group (H24–C-H25), as well as two double doublet between 3.56–
.27 ppm related to the methylene protons (H30–C-H31) of isoxa-
3
zoline ring. In addition a multiplet between 5.40 and 5.30 ppm is
assigned to the proton (C–H29) of isoxazoline ring. The calculated
chemical shifts values of the protons (H24–C-H25 (4.52–4.16 ppm)),
(
H30–C-H31 (3.99–3.45 ppm)) and (C–H29 (5.36 ppm)) were ob-
Fig. 5. HOMO and LUMO computed by B3LYP/6–31G(d, p).
6

M. Aarjane, S. Slassi, A. Ghaleb et al.
Journal of Molecular Structure 1231 (2021) 129921
Table 4
reactivity, more polarized and low kinetic stability, and vice versa
for compounds possess high energy gap [36].
Global Reactivity Properties of the (3) compound.
Parameters
B3LYP/6–31G(d.p)
Frontier orbitals of 10-{[3-(4-chlorophenyl)-4,5-dihydro-1,2-
oxazol-5 yl]methyl} acridone (3), which has 202 electrons, 101
occupied and 189 unoccupied virtual molecular orbitals, was ob-
tained using DFT/B3LYP method with 6–31G(p) basis set. The
EHOMO
-5.69 eV
-1.90 eV
5.69 eV
1.90 eV
3.79 eV
1.89 eV
0.26 eV
-3.79 eV
3.78 eV
ELUMO
Ionization potential (I)
Electron affinity (A)
Electronegativity (χ)
Chemical hardness (η)
Chemical softness (S)
Electronic chemical potential (μ)
Electrophilicity index (ω)
energy value of the band gap is calculated as ꢀE = E
LUMO
-
HOMO
E
= -3.79 eV, this means that the compound (3) has quite
stable feature [37]. Regarding the distributions charges of HOMO
orbitals, Fig. 5 shows that electron density is located on the
acridone ring, with small distribution on the isoxazoline ring
and the electron cloud of the LUMOs is highly populated in the
acridone ring (Fig. 5). Green and red colors distributions signify
negative and positive phase in molecular orbital wave function,
respectively.
Global reactivity descriptors act as a bridge to understand the
relationship between stability of the structures and global chem-
ical reactivity [38]. The chemical reactivity descriptions of molec-
ular orbitals such as electro-negativity (χ), chemical hardness (η),
chemical potential (μ) and softness (S) defined as follows:
(
I + A)
χ =
η =
μ =
S =
2
(
I − A)
2
−
(I + A)
2
1
Fig. 6. Electrostatic potential (MEPs) map of compound 3 calculated at B3LYP/6
1G(d,p) method and basis set.
3
2η
Where A and I are the electron affinity and ionized energy of the
compound (3). A and I can be portrayed during LUMO energy as
A=-ELUMO and HOMO energy as I=-EHOMO. The chemical hard-
ness and softness properties were used to compute the reactivity
and molecular stability. The calculation of electro-negativity (χ),
chemical hardness (η), chemical potential (μ) and softness (S) of
compound (3) were found to be 3.79 eV, 1.89 eV, -3.79 eV, and
theoretical obtained values for 1H and 13C NMR chemical shift are
presented in Fig. 4. In this study, the observed results showed a
good agreement between the theoretical and experimental 1H and
13C NMR chemical shifts.
3
.9. Frontier molecular orbitals
0
.26 eV respectively (Table 4).
Frontier molecular orbitals, represented with the lowest unoc-
cupied molecular orbital (LUMO) and highest occupied molecular
orbital (HOMO), play an interesting role in describing physical and
chemical activities of molecules. Normally, compounds containing
small energy gap (ꢀE = EHOMO - ELUMO) present higher chemical
3.10. Molecular electrostatic potential (MEP)
MEP represent the charge distributions of molecules. These
maps afford a visual method to understand the charged regions
Fig. 7. Mulliken Plot of compound (3).
7

M. Aarjane, S. Slassi, A. Ghaleb et al.
Journal of Molecular Structure 1231 (2021) 129921
as well as the relative polarity of a molecule [39]. On the basis of
these maps it is possible to study the nucleophilic and electrophilic
reactive sites of molecules [40]. To examine chemical reactivity,
the molecular electrostatic potential surface analysis of 10-{[3-(4-
chlorophenyl)-4,5-dihydro-1,2-oxazol-5 yl]methyl} acridone (3) was
calculated at the B3LYP/6–31G(d,p) level. The MEP Map of the
studied compound is shown in Fig. 6. We remarked from this map
that different colors are presented: blue-green-yellow-orange-red,
which are associated to the electronic density distribution. Blue
color represented the maximum positive potential and the nega-
tive regions (red and yellow) represented the maximum negative
potential. The MEP Map showed that the positive regions are fo-
cused on the hydrogen atoms of the isoxazoline ring, while the
negative regions are around the oxygen atoms (O21 and O34) of the
acridone and isoxazoline rings. The bleu areas are suitable sites for
the nucleophilic attack. In contrast, the red regions signified the
sites of the maximum reactivity towards electrophilic attacks.
Acknowledgement
The authors gratefully acknowledged to Research team Molecu-
lar Chemistry and Bioactive Molecules, Faculty of Science, Moulay
Ismail University, for providing necessary facilities to carry out the
research work. The authors also acknowledge to National School of
Agriculture Meknes, for providing the facility for access to the mi-
crowave
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