Structure and absolute configuration of some 5-chloro-2-methoxy-N-phenylbenzamide derivatives

Article abstract of DOI:10.1016/j.saa.2017.06.068

The absolute configuration of 5-chloro-2-methoxy-N-phenylbenzamide single crystal [compound (1)] and the effect of introducing –[CH₂]_n–, n?=?1,2 group adjacent to the amide group [compounds (2) and (3)], were studied. Furthermore, the replacement of the methoxy group with a hydroxy group [compound (4)] was defined. Proton and carbon-13 NMR spectrometer were used to record the structural information of the prepared compounds. X-ray single crystal diffractometer were used to elucidate the 3D structural configurations. Intensity data for the studied compounds were collected at room temperature. The X-ray data prove that compound (1) is almost planar, with maximum r.m.s. deviations of 0.210(3)?? corresponds to C13. This planarity starts to disturb by adding –[CH₂]_n–, n?=?1,2 groups between the NH group and the phenyl ring in compounds (2) and (3), respectively. By replacing the OCH₃ group by an OH group in compound (4), the plane of the chlorophenyl moiety is nearly perpendicular to that of the phenyl ring. Such new structural configurations were further illustrated by the infrared, and ultraviolet-visible spectroscopy measurements in the frequency range 400–4000?cm^??1 and 190–1100?nm, respectively. Spectroscopic analyses were verified with the help of molecular modeling using density functional theory. The estimated total dipole moment for the prepared compounds reflects its ability to interact with its surrounding molecules. The higher dipole moment for a given structures is combined with the higher reactivity for potential use in medicinal applications.

Full text of DOI:10.1016/j.saa.2017.06.068

Structure and absolute configuration of some 5-Chloro-2-methoxy-N-
phenylbenzamide derivatives.
Alaaeldin M F Galal, Elsayed M. Shalaby, Ahmed Abouelsayed, Med-
hat A. Ibrahim, Emad Al-Ashkar, Atef G Hanna
PII:
DOI:
Reference:
S1386-1425(17)30546-2
doi:10.1016/j.saa.2017.06.068
SAA 15284
To appear in:
Received date:
Revised date:
Accepted date:
21 December 2016
5 June 2017
30 June 2017
Please cite this article as: Alaaeldin M F Galal, Elsayed M. Shalaby, Ahmed Abouel-
sayed, Medhat A. Ibrahim, Emad Al-Ashkar, Atef G Hanna, Structure and abso-
lute configuration of some 5-Chloro-2-methoxy-N-phenylbenzamide derivatives., (2017),
doi:10.1016/j.saa.2017.06.068
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ACCEPTED MANUSCRIPT
Structure and absolute configuration of some
5
-Chloro-2-methoxy-N-phenylbenzamide derivatives.
a
b
c
c
c
Alaaeldin M F Galal , Elsayed M. Shalaby , Ahmed Abouelsayed* , Medhat A. Ibrahim , Emad Al-Ashkar , Atef G
Hannaa
aChemistry of Natural Compounds Department, Drug and Pharmaceutical Industries Research Division, National Research Centre, 33 El
Bohouth st. (former El Tahrir st.) - Dokki - Giza - Egypt - P.O. 12622.
b
X-Ray Crystallography Laboratory, Physics Division, National Research Centre, 33 El Bohouth st. (former El Tahrir st.) - Dokki - Giza -
Egypt - P.O. 12622.
c
Spectroscopy Department, Physics Division,National Research Centre, 33 El Bohouth st. (fromer El Tahrir st.)- Dokki - Giza - Egypt -
P.O. 12622
Abstract
The absolute configuration of 5-Chloro-2-methoxy-N-phenylbenzamide single crystal [compound (1)] and the effect of
introducing -[CH2]n-, n=1,2 group adjacent to the amide group [compounds (2) and (3)], were studied. Furthermore,
the replacement of the methoxy group with a hydroxy group [compound (4)] was defined. Proton and carbon-13
NMR spectrometer were used to record the structural information of the prepared compounds. X-ray single crystal
diffractometer were used to elucidate the 3D structural configurations. Intensity data for the studied compounds were
collected at room temperature. The X-ray data prove that compound (1) is almost planar, with maximum r.m.s.
˚
deviations of 0.210(3) A corresponds to C13. This planarity starts to disturb by adding -[CH2]n-, n=1,2 groups between
the NH group and the phenyl ring in compound (2) and (3), respectively. By replacing the OCH3 group by an OH group
in compound (4), the plane of the chlorophenyl moiety is nearly perpendicular to that of the phenyl ring. Such new
structural configurations were further illustrated by the infrared, and ultraviolet-visible spectroscopy measurements in
−
1
the frequency range 400-4000 cm and 190-1100 nm, respectively. Spectroscopic analyses were verified with the help
of molecular modeling using density functional theory. The estimated total dipole moment for the prepared compounds
reflects its ability to interact with its surrounding molecules. The higher dipole moment for a given structures is combined
with the higher reactivity for potential use in medicinal applications.
Keywords: 5-Chloro-2-methoxy-N-phenylbenzamide, NMR, Single crystal, FTIR, UV-Vis, Molecular
Modeling.
2
010 MSC: 00-01, 99-00
1
. Introduction
-Chloro-2-methoxy-N-phenylbenzamide
backbone structure of polypeptides and proteins. The
trans-planar conformation (I) of the peptide link has
long been accepted as dominant in N-mono-substituted
straight chain amides [2, 3] and proteins [4], whereas the
cis-planar conformation (II) has been proposed [5] for
some of the residues of fibrous proteins.
5
derivatives
were chemically synthesized for possible use in phar-
maceutical applications [1]. The conformation of the
amide group is of prime importance in determining the
∗
Ahmed Abouelsayed
N-alkyl-amides, R-CONH-R’, provided R and R’ are not
both larger than Et and i-Pr, both cis and trans conform-
July 1, 2017
Email addresses: as.abouelsayed@gmail.com (Ahmed
Abouelsayed*), a−sobhi77@yahoo.com (Ahmed Abouelsayed*)
Preprint submitted to Journal of LAT X Templates
E

ACCEPTED MANUSCRIPT
methoxy-N-phenylbenzamide (compound (1)) was pre-
pared and investigated and followed by studying the ef-
fect of adding -[CH2]n- ,n=1,2 on the configuration. Fur-
thermore, the methoxy group was replaced with a hydroxy
group and its effect on the absolute configuration was stud-
ied. The UV-Vis spectral analysis were used to investigate
the redistributions of the charges over the groups of the dif-
ferent compounds due to different configurations. The net
reactivity for the new structural configuration have been
studied theoretically for possible use in pharmaceutical ap-
plications.
N
N
H
(I)
(II)
ers co-exist in solution. The abundance ratios are strongly
dependent on steric size but the trans form is always pre-
dominant [6]. Experimentally, it has been reported that
the IR spectrum of the trans amide group is considerably
different from that of the cis amide group, e.g. the N-H
stretching vibration of the monomeric trans amide group
is observed at higher wavenumbers by about 20-40 cm 1
−
2. Experimental
as compared to the cis amide group [6].
All materials, reagents and solvents were purchased from
Molecular modeling with different level of theories and
FTIR are combined together to understand the molecu-
lar structure of many systems and molecules especially
for those of biological origin [7, 8, 9]. Molecular model-
ing at DFT level was conducted to follow up the effect
of substitution upon the AZT drug to avoid its adverse
impact [10]. Molecular modeling was conducted to study
fullerene based system which is then modified to act as
HIV-1 Protease Inhibitors [11]. The possible application
of Chitosan-Functionalized silicon as sensor for DNA is
tested with molecular modeling [12]. Both Peptidomimetic
and Macrocyclic NS3 were subjected to molecular model-
ing analyses to act as HCV protease inhibitors [13].
Within this study, infrared spectroscopy have been
used as a diagnostic tool for studying the existence of
the cis and trans conformations. In addition, the NMR
spectroscopy have proved that the site A for structure
Sigma-Aldrich, Merck, fisher chemicals, Lab- Scan ana-
lytical sciences and were used as received. 1H and 13C-
NMR spectra were recorded at 298K on a JEOL ECA-
1
5
1
00 spectrometer ( H at 500.16 MHz and 13C-NMR at
25.76 MHz), and were processed using the Bruker Top-
spin 3.2 software. H and 13C-NMR spectra are referenced
to H signals of residual nondeuterated solvents and 13C
signals of the deuterated solvents respectively. 1H-NMR
signals are reported with chemical shift values δ (ppm),
multiplicity (s=singlet, d=doublet, t=triplet, q=quartet,
m=multiplet and br=broad), relative integral, coupling
constants J (Hz) and assignments. Mass spectra were
recorded on AJEOL DART+ HI RESOLUTION carried
out using ESI. Melting points were determined on an Elec-
trothermal IA9100 digital melting point apparatus and are
uncorrected.
1
1
General synthetic procedures of 5-chloro-2-
methoxy benzamide derivatives (1-3): Triethyl
amine (1.5 mL, 10.7 mmol) was added slowly to a
solution of 5-chloroanisic acid (2.0 g, 10.7 mmol) in
dichloromethane (DCM,20 mL) at room temperature.
Ethyl chloroformate (1.02 mL, 10.7 mmol) was added
dropwise to the reaction mixture which was stirred for 1h
at room temperature. The appropriate amine (10.7 mmol)
(
III) and B for structure (IV) are magnetically non-
equivalent. The absolute configuration of 5-Chloro-2-
R1
O
R1
O
R (B)
H
2
N
N
H
R (A)
2
(
III)
(IV)
2

ACCEPTED MANUSCRIPT
was added dropwise to the reaction mixture which was
5-Chloro-2-hydroxy-N-benzylbenzamide [com-
pound(4)]: 5-chloro-2-methoxy-N-benzylbenzamide (1.1
g, 4 mmol, 2) and sodium cyanide (0.29 g, 6 mmol)
were added to anhydrous dimethyl sulfoxide (5 ml). The
reaction mixture was refluxed for 1 hr. with stirring, and
then added to cold water (50 ml). The solution was acid-
ified with 1N HCl and extracted with methylene chloride
several times. The collected extract was evaporated under
reduced pressure to yield the benzamide derivative (4)
which was crystallized from methanol to give colourless
stirred at room temperature for further 2 h. Distilled wa-
ter (20 mL) was added. The organic layer was separated,
dried over anhydrous sodium sulfate, and evaporated un-
der reduced pressure. The residue was crystallized from
methanol to give benzamide derivatives (1-3) [1].
5
-Chloro-2-methoxy-N-phenylbenzamide [com-
pound(1)]: Colourless transparent Prism crystals, yield
◦
1
9
7
1
4%, mp 115 C. H-NMR (DMSO-d6) δ 3.92 (s, 3H, CH3),
.09 (t,1H, J=7.4 Hz, Ar-H), 7.13 (dd, 1H, J=8.2 and
.8 Hz, Ar-H), 7.27 (d,1H, J=1.8 Hz, Ar-H), 7.34 (t, 2H,
◦
transparent Prism crystals, yield 52%, mp 125 C [14].
1H-NMR (CDCl3) δ 4.6(d, 2H, J=5.75 Hz,CH2), 6.57
J=7.9 Hz, Ar-H), 7.63 (d, 1H, J=8.2 Hz, Ar-H), 7.72 (d,
H, J=7.7 Hz, Ar-H), 10.13 (br, s, 1H, NH) [1]. 13C-NMR
DMSO-d6): δ 56.7, 114.8, 125, 126.4, 127.2, 128, 128.7,
(
(
br,s, 1H, NH ),6.94 (d,1H, J=8.6 Hz, Ar-H), 7.31-7.37
m,7H,Ar-H), 12.23 (s, 1H, OH). 13C-NMR (CDCl3):
2
(
30.2, 132.1, 140.1, 156.5, 164.6. MS(ESI) m/z [M+H]+
δ 43.9, 115.1, 120.3, 123.4, 125.1, 128.1, 129.1, 134.3,
1
+
37.1, 160.2, 168.8. MS(ESI) m/z [M+H]+ calcd. for
1
calcd. for C14H13ClNO2 262.0629 found 262.0578 [1].
+
C14H13ClNO2 262.06347 found 262.06120.
5
-Chloro-2-methoxy-N-benzylbenzamide [com-
pound(2)]: Colourless transparent Prism crystals, yield
2
.1. Samples Characterization
◦
1
9
7%, mp 73 C. H-NMR (DMSO-d6) δ 3.85 (s, 3H, CH3),
.45(d, 2H, J=5.75 Hz,CH2),7.13 (d,1H, J=7.5 Hz, Ar-
4
Intensity data for the studied compounds were collected
H), 7.21 (d,2H, J=3.8 Hz, Ar-H), 7.29 (s, 3H, Ar-H), 7.48
dd, 1H, J= 6.85 and 1.5 Hz, Ar-H), 7.65(d, 1H, J=2.5
Hz, Ar-H), 8.76 (s, 1H, NH). 13C-NMR (DMSO-d6): δ
at room temperature (298 K) on an Enraf-Nonius 590
diffractometer with a Kappa CCD detector using graphite
(
˚
monochromated Mo-Kα (λ = 0.71073A) radiation [15].
4
1
3.3, 56.8, 114.6, 125, 125.4, 127.2, 127.6, 128.8, 130.2,
Data were recorded in the rotation mode using the φ and ω
32.1, 140, 156.4, 164.4. MS(ESI) m/z [M+H]+ calcd. for
◦
◦
◦
scan technique with 2θ max = 30.068 ,27.069 ,30.063 and
+
◦
C15H15ClNO2 276.07912 found 276.08732.
25.025 for compounds (1), (2), (3) and (4), respectively.
5
-Chloro-2-methoxy-N-phenylethylbenzamide
Data were corrected for absorption effects using the multi-
scan method SADABS [16]. The structures were solved
by direct methods using SIR92 [17]. The refinement was
carried out by the full-matrix least-squares method with
anisotropic displacement parameters for all non-hydrogen
atoms based on F2 using CRYSTALS [18]. The hydro-
gen atoms were positioned geometrically in their ideal-
ized positions [19]. The general-purpose crystallographic
tool PLATON [20] was used for the structure analysis and
presentation of the results. ORTEP-3 for Windows [21]
and MERCURY [22] programs were used for molecular
graphics representations. Details of the data collection
[
compound(3)]:Colourless transparent Prism crystals,
◦
1
yield 87%, mp 62 C. H-NMR (DMSO-d6) δ 2.81(t, 2H,
J=7 Hz,CH2), 3.49(q, 2H, J=6.85 Hz,CH2), 3.76 (s, 3H,
CH3) ,7.09 (d,1H, J=7.5 Hz, Ar-H), 7.18 (d,2H, J=6.9
Hz, Ar-H), 7.22(d, 2H, J=6.85 Hz, Ar-H), 7.27 (dd, 1H,
J=6.85 and 1.15 Hz, Ar-H), 7.44(dd, 1H, J= 6.85 and
1
1
5
1
.5, Hz, Ar-H), 7.68(d, 1H, J=2.5 Hz, Ar-H), 8.22 (d,
H, J=4.6 Hz, NH). 13C-NMR (DMSO-d6): δ 35.5, 42.3,
6.7, 114.6, 125, 125.4, 126.7, 128.9, 129.2, 130.2, 132.1,
39.9, 156.3, 163.9. MS(ESI) m/z [M+H]+ calcd. for
+
C16H17ClNO2 290.09477 found 290.08985.
3

ACCEPTED MANUSCRIPT
(a)
Figure 1
O
C
CL
NH
(CH2)n
(b)
OR
(a) n= 0 , R=CH3
(b) n= 1 , R=CH3
(c) n= 2 , R=CH3
(d) n= 1 , R=H
(
c)
(d)
Figure 1: (a-d) An ORTEP view of 7a showing the atom-numbering scheme for compounds (1), (2), (3) and (4), respectively. Displacement
ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
and refinement are given in Table 1. The infrared mea-
surements were carried out at room temperature in the
sion through sample, while light transmitted through the
air is used as reference. The intensity Isample(ω) of the
radiation transmitted through the sample and the inten-
sity Iref (ω) of the radiation transmitted through the air
were measured. From Isample(ω) and Iref (ω) the trans-
mission and absorption spectra were calculated accord-
ing to T(ω)=Isample(ω)/Iref (ω) and A(ω)=-log10T(ω), re-
frequency range 400-4000 cm 1 at a resolution of 4 cm
−
−1
after 64 scans using Fourier transform infrared spectrom-
eter FT/IR 6100 (Jasco, Japan). A matrix containing
sample and potassium bromide (KBr) to make a pellet
with about 1 mm thickness is used for obtaining transmis-
4

ACCEPTED MANUSCRIPT
Compound (1)
Compound (2)
Compound (3)
Compound (4)
Chemical formula
C14H12ClNO2
261.71
C15H14ClNO2
275.73
C16H16ClNO2
289.76
C14H12ClNO2
261.71
Mr
Crystal system, space group
Monoclinic, P21/n
Orthorhombic, Pbca
Monoclinic, P21/c
Monoclinic, C2/c
a, b, c( ˚A )
7.3085(3),12.0581(7),14.6033(7) 13.316(3),8.3497(12),24.568(4) 11.1735(4),8.4627(3),15.6152(6) 27.307(3),6.6770(9),16.3813 (19)
◦
α, β, γ( )
3
90,103.888(4),90
1249.32 (6)
4
90,90,90
2731.5 (5)
8
90,99.517(2),90
1456.22 (6)
4
90,123.791(3),90
2482.2 (3)
8
V ( ˚A )
Z
Radiation type
µ(mm1)
Mo Kα
Mo Kα
Mo Kα
Mo Kα
0.30
0.28
0.26
0.30
Crystal size (mm)
Tmin, Tmax
0.32×0.24×0.18
0.87, 0.95
3447, 3447, 1958
0.705
0.36×0.22×0.18
0.79, 0.95
2859, 2409, 896
0.595
0.40×0.36×0.22
0.91, 0.94
4157, 4157, 1941
0.705
0.42×0.36×0.24
0.93, 0.93
7434, 2207, 1537
0.598
No. of measured, independent and observed [I > 2.0σ(I)] reflections
1
(
sinθ/λ)max( ˚A )
R[F2 > 2σ(F2)], wR(F2), S
0.048, 0.104, 0.99
1958
0.052, 0.133, 1.01
896
0.058, 0.104, 1.04
1941
0.044, 0.86, 0.93
1537
No. of reflections
No. of parameters
3
166
175
184
169
∆
ρmax, ∆ρmin(e ˚A )
0.20, 0.27
0.13, 0.13
0.44, 0.25
0.19, 0.26
CCDC Number
1520653
1520654
1520655
1520656
Table 1: Crystal data and refinement details for compounds 1, 2, 3 and 4.
correlation functional B3LYP [24, 25, 26] using 6-31G(d,p)
basis set. The optimized structures were then subjected to
vibrational spectra calculations at the same level of the-
ory. Some other physical parameters were calculated also
at the same level of theory such as total dipole moment
and HOMO/LUMO band gap energy.
Figure 2
3. Results and discussion
3
.1. Single crystal X-ray studies
Figure 2: Overlay diagram of the studied compounds: red (1), green
2), blue (3) and yellow (4).
(
Fig. 1 (a-d) showed ORTEP diagrams for the stud-
ied structures for compounds (1), (2), (3) and (4), re-
spectively; the asymmetric unit in each comprises one
molecule. Generally, the geometrical parameters of the
studied compounds are comparable with each other and
with structures having same moieties [27, 28, 29, 30]. Com-
pound (1) seems to be almost planar, with maximum r.m.s.
spectively. The Uv-Vis absorption spectra of samples were
recorded using V-630 UV-VIS Spectrophotometer (Jasco,
Japan). The samples spectra were recorded at room tem-
perature in the wavelength range 190 - 1100 nm. The sam-
ples were sonicated in methanol solution, and then about 3
mL of the sample and methanol mixture were transferred
to the quartz curette to record the samples spectra, where
the quartz curette filled with pure methanol were used
as a reference. All the studied structures are subjected
to energy optimization using GAUSSIAN09 softcode [23]
at Spectroscopy Department, National Research Centre,
Egypt. Calculations were performed with the hybrid func-
tional Becke, three-parameter, Lee-Yang-Parr exchange-
˚
deviations of 0.210(3) A corresponds to C13. This pla-
narity starts to disturb by adding CH2 group between the
NH group and the phenyl ring in compound (2), this can be
noticed from the value of the dihedral angle between the
plane containing the chlorophenyl moiety and that con-
◦
taining the phenyl ring which is 48.23(5) .
The same can be noticed for compound (3) that has
more CH2 group between the NH group and the phenyl
5

ACCEPTED MANUSCRIPT
Figure 3
(
a)
(b)
(
c)
(d)
Figure 3: Packing diagram for compounds (1), (2), (3) and (4) illustrated in the figure from (a-d), respectively, showing the supramolecular
assembly and the H-bonds as dashed lines.
ring than compound (2). The dihedral angle between the
plane containing the chlorophenyl moiety and that con-
set of intra- and intermolecular hydrogen bonds as listed
in table 2. The existence of such hydrogen bonding results
in forming set of supramolecular chains as illustrated in
Fig. 3 (a-d). Furthermore, molecules in compound (4) are
stabilized by the existence of the C15-H151... π interactions
as listed in table 2. The C-π-bonds of compound (4) are
further illustrated by showing the supramolecular assem-
bly of this compound as a dashed lines as demonstrated in
Fig. 4.
◦
taining the phenyl ring in this compound is 38.17(4) . For
compound (4), which is similar to compound (2) but with
replacing the OCH3 group by an OH group, the plane of
the chlorophenyl moiety is nearly perpendicular to that of
◦
the phenyl ring (the dihedral angle is 73.35(3) ). These ob-
servations are also clear by overlaying the molecular skele-
tons obtained from X-ray diffraction for compounds (1),
(
2), (3) and (4) (see Fig. 2).
The compounds (1), (2), (3) and (4) are stabilized by
6

ACCEPTED MANUSCRIPT
Compound (1)
D-H...A
Fig. 5 (a-d) shows the FTIR absorption spectra of the 5-
Chloro-2-methoxy-N-phenylbenzamide (compound(1)) as
compared with the other three different compounds. The
hydrogen bonded NH stretching vibrations of compound
D-H
H...A
D...A
D-H...A
C(13) –H(131) ..Cl(1)i
C(8) –H(81) ..O(1)ii
N(1) –H(11) ..O(2)
C(3) –H(31) ..O(1)
C(13) –H(131) ..O(1)
0.96
0.96
0.85
0.96
0.96
2.86
2.51
3.565(2)
3.447(3)
2.670(3)
2.715(3)
2.851(3)
131.2
166
1.95(2)
2.37
141.1(13)
101
(
1) (Fig. 5 (a)) observed at 3346 cm 1 are shifted to higher
−
2.26
119
wavenumber for compounds (2), (3) and (4). According
to the XRD results, compound (1) is almost planar. The
higher shift of the hydrogen bonded NH stretching vibra-
tions in compounds (2), (3) and (4) can be attributed to
the disturbance in the planar structure by adding CH2
group between the NH group and the phenyl ring in com-
pounds (2), (4) and by adding more CH2 group in com-
pound (3). The free rotation of the NH group in com-
pounds (2), (3) and (4) increase the distance of the in-
termolecular hydrogen bonds and shift the NH stretching
vibrations to higher energy. The shifts of the NH stretch-
ing vibrations to the higher wavenumber in compounds
Compound (2)
C(11) –H(111) ..O(1)i
0.96
0.86(3)
0.86(3)
0.96
2.64
2.21(3)
2.29(3)
2.54
3.592(4)
2.961(6)
2.766(6)
2.879(7)
2.826(7)
170
141.1(13)
166.0(12)
101
N(1) –H(11) ..O(1)ii
N(1) –H(11) ..O(2)
C(9) –H(91) ..N(1)
C(15) –H(151) ..O(1)
0.96
2.42
119
Compound (3)
C(3) –H(31) ..Cl(1)i
C(5) –H(51) ..Cl(1)ii
N(1) –H(11) ..O(2)
C(3) –H(31) ..O(1)
0.96
0.96
2.95
2.95
3.906(2)
3.694(4)
178
135
0.870(18) 2.006(19) 2.692(3)
135.0(18)
101
0.96
2.36
2.712(3)
Compound (4)
N(1) –H(11) ..O(2)i
C(13) –H(131) ..O(1)
O(2) –H(22) ..O(1)
C(15) –H(152) ..O(1)
0.85(3)
0.99
2.20(2)
2.56
2.946(3)
3.468(4)
2.528(3)
2.794(3)
147(2)
153
0.84(4)
0.97
1.76(3)
2.41
153(3)
103
(
2), (3) and (4) indicates the presence of the trans amide
D − H...Cg
D − H
0.97
H...Cg
D...Cg
D − H...Cg
C15-H151...Cg1ii
group configuration [6]
2.79
3.477(3)
129
◦
Figure5
Table 2: Hydrogen-bond geometry and non-bonding contacts ( ˚A , )
0.8
0.6
0.4
0.2
0.0
(
d) Compound (4)
5-Chloro-2-hydroxy-N-benzylbenzamide
for compounds 1, 2, 3, 4.
H
CL
..
C
N
CH
2
O
Figure 4
O-H
5
5
5
5
00
1000
1500
2000
2500-
3000
3500
4000
4000
4000
4000
1
Wavelength (cm )
0
0
0
0
0
.8
.6
.4
.2
.0
(c) Compound (3)
5-Chloro-2-methoxy-N-phenylethylbenzamide
O
CL
..
C
N
CH
2
CH
2
H
OCH
3
00
1000
1500
2000
2500-
3000
3500
1
Wavelength (cm )
1.2
0.8
0.4
0.0
(b) Compound (2)
5-Chloro-2-methoxy-N-benzylbenzamide
O
CL
.
.
C
N
H
CH2
O-CH
3
00
1000
1500
2000
2500-
3000
3500
1
Figure 4: Packing diagram of compound (4) showing the supramolec-
Wavelength (cm )
1.2
0.8
0.4
0.0
ular assembly and the C-pi-bonds as dashed lines.
(a) Compound (1)
5-Chloro-2-methoxy-N-phenylbenzamide
O
CL
..
C
N
H
O-CH
3
3
.2. Spectroscopic analyses
00
1000
1500
2000
2500-
3000
3500
1
Wavelength (cm )
Spectroscopic analyses is conducted first with FTIR
spectroscopy then UV-Vis spectroscopy and verified with
the help of molecular modeling using B3LYP/6-31G(d,p).
Figure 5: FTIR absorption spectra for the studied structures namely
compounds (1), (2), (3) and (4).
7

ACCEPTED MANUSCRIPT
∗
The C=O vibrational stretching mode for the 5-
Chloro-2-methoxy-N-phenylbenzamide [compound(1)] are
observed, and these are assigned to the n −→ σ for C=O
∗
∗
group, n −→ σ for N-H group, and n −→ π for C=O
group, respectively. In compounds (2), (3), (4), the n
−→ σ∗ transition for N-H group were shifted to higher
energy indicating that the distance between the n state
observed at 1666 cm 1, while this band are shifted to
−
lower wavelength at about 1633 cm 1, 1654 cm and 1643
−
−1
−
1
cm for compounds (2), (3) and (4), respectively. It is
obvious from Fig. 5 (b), the lower shift for the C=O mode
is strong for coumpund (2) as compared to compounds (3),
∗
and σ state increases which might be due to the free ro-
tation of the N-H group. The increase the distance of the
hydrogen bond (marked as a red dashed line in Fig. 6)
due to the free rotation of the N-H group yields to elec-
tron confinement over N-H group. This might shift the n
(
4). The symmetric and asymmetric stretching vibration
of the CH2 group could be recognized at 2947 cm 1 and
−
−
−1
2
848 cm 1. The IR bands at 1598 cm and 1543 cm
−1
∗
were assigned to the vibrational stretching mode of the
C=C in the benzene ring. The vibrational bands at 1034
−→ σ transition for N-H group to higher energy in com-
pounds (2), (3). In compound (4) there is no hydrogen
bond related to the N-H group, which produce more elec-
tron confinement over the N-H group and shifts more to
higher energy. It is also clear from the figure that the en-
−
1
−1
cm and 1239 cm are attributed to the C-O stretching
−
1
−1
modes. The two modes 1401 cm and 910 cm could be
ascribed to C-O-H in plane bending and O-H out of plane
−
1
∗
bending vibration. The two signals at 1270 cm and 1240
ergy of the n −→ π transition for C=O group were shifted
−
1
cm could be assigned to C-N stretching vibration. The
slightly to higher energy and gain more intensity in com-
−
1
−1
IR bands at 1469 cm and 1440 cm were ascribed to
the asymmetric and symmetric C-H stretching vibrations
pounds (2), (3) while it shifts to lower energy in compound
∗
(4). Such lower shift for the n −→ π transition for C=O
−
1
of CH3-O. The peaks at 3001-3106 cm were attributed
to the vibrational stretching mode of the aromatic O-C-H
group present in the benzene ring.
group in compound (4) might be due to the formation of
hydrogen bond with the O-H group linked with the Phenyl
ring. This hydrogen bond is marked with red dashed line
(
See Fig. 6 compound (4)).
Figure 6
4
3
2
1
0
O
C
CL
..
n* n*
n*
C O
N
As indicated in XRD data the changes in the struc-



1
2
H
C O
N
O-CH
3
tural parameters are recorded in case of COOH and NH2
groups as a result of introducing CH2 into the studied
structures. Molecular modeling at density functional the-
ory level could follow up the changes in the geometrical
as well as vibrational parameters to confirm the data ob-
tained with XRD and FTIR. It is clear from table 3 that
there are no noticeable changes in the bond lengths. N-H
and C=O while small change is regarded in the CN bond
length with slight change in the bond angles HNC and
OCC. These findings confirm those obtained with XRD.
Table 4 presents the values of total dipole moment and
HOMO/LUMO band gap energy beside the characteris-
tic bands for both COOH and NH2. Total dipole mo-
ment of a given structure reflects its ability to interact
O
C
CL
..
N
CH
2
H
O-CH
3
O
C
CL
..
N
CH
2
CH
2
3
4
H
OCH
3
H
CL
..
C
N
CH
2
O
O-H
2
00
250
300
350
400
450
500
Wavelength (nm)
Figure 6: UV absorption spectra for the studied structures namely
compounds (1), (2), (3) and (4).
Fig. 6 shows the Uv-Vis absorption spectra of the
four different compounds. For 5-Chloro-2-methoxy-N-
phenylbenzamide (compound(1)), three strong optical ab-
sorption bands at 228 nm, 268 nm, and 304 nm can be
8

ACCEPTED MANUSCRIPT
Figure7
a)
(
(c)
(b)
(d)
Figure 7: B3LYP/6-31G(d,p) calculated structures indicating the direction of net dipole moment as blue arrow then mapping the
HOMO/LUMO orbitals and finally the calculated IR spectra for the compounds (1),(2), (3) and (4) as illustrated in the figure from (a-
d), respectively.
with its surrounding molecules or in other words higher
dipole moment is attributed to higher reactivity of the
given compound. The reactivity is also increased with de-
creasing band gap energy. It is clear that total dipole mo-
ment is decreased as a result of introducing CH2 into the
compounds with slight increase in band gap energy. The
change in these two parameters means that the compounds
are subjected to redistribution in their charges while the
net dipole moment is changed its directions. As shown
in Fig. 7, the net dipole moment is directed parallel to
C=O then became in other directions for the other three
compounds. The figure indicated also the HOMO/LUMO
band gap energy, then the calculated IR spectra. It is
worth to mention that, the difference in the studied spec-
tra are recorded only in terms their characteristic bands
NH and C=O while other bands are not affected. Cor-
relating the data in Fig. 7 and table 4 revealed that. A
shift is then noticed in the N-H toward lower wavenumbers.
While C=O shows shift slightly toward higher wavenum-
ber then to lower wavenumbers on going from compounds
(2) to (4). It is clear that introducing CH2 has nearly
no change in the geometrical parameters as stated earlier
by XRD and confirmed with molecular modeling calcu-
lations. While the studied compounds show a change in
their physical parameters. This may cause the changes
in the UV-Vis spectra as indicated earlier according to
9

ACCEPTED MANUSCRIPT
C-N
N-H
N-C C=O C-C
C-Cl
HNC OCC
charges over the groups of the different compounds due to
different configurations. Furthermore, spectroscopic anal-
yses were verified with the help of molecular modeling us-
ing density functional theory. The estimated total dipole
moment for the prepared compounds reflects its ability to
interact with its surrounding molecules. The higher dipole
moment for a given structures is combined with the higher
reactivity for potential use in medicinal applications.
1
2
3
4
-1 1.409 1.012 1.369 1.229 1.519 1.758 115.6 119.6
-1 1.461 1.014 1.366 1.227 1.512 1.759 112. 5 120.7
-1 1.456 1.014 1.369 1.229 1.508 1.760 112.7 121.1
-1 1.465 1.009 1.358 1.250 1.487 1.761 117.1 120.8
Table 3: B3LYPl/6-31G(d,p) calculated bond lengths in ( ˚A ) and
◦
bond angle in ( ) for the studied models.
Total dipole moment Band gap energy
NH
C=O
1
2
3
4
-1
-1
-1
-1
6.259
2.344
4.229
2.8152
4.452
5.766
5.228
4.642
1598.4 1753.0
1487.4 1761.7
1493.6 1754.5
1565.8 1710.5
5. Acknowledgment
The authors would like to thank Colleagues on the moral
support provided during the completion of this work. Also,
The authors thank all the gratitude National Research
Center(NRC), Dokki, Giza, Egypt on the financial sup-
port provided by the project number 11010324.
Table 4: B3LYPl/6-31G(d,p) calculated total dipole moment as De-
bye, HOMO/LUMO band gap energy as eV, the NH; C=O frequency
−
1
as cm
for the studied models.
the redistribution in the charges and the changes in the
HOMO/LUMO band gap energy. This is also responsible
for the change in the intra-molecular distance the possible
coordination between the H-bonding of COOH and its sur-
rounding molecules this in turn makes the N-H group in
this configuration more active according to the introduc-
tion of the CH2 then makes the compounds (2) and (3)
more stable while the compound (4) is more stable and
more reactive in terms of its lower band gap energy and
higher total dipole moment as compared with compounds
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11

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Graphical Abstract
Overlay diagram of the studied compounds:
(
(
(
I) Red: 5-Chloro-2-methoxy-N-phenylbenzamide.
II) Green : 5-Chloro-2-methoxy-N-benzylbenzamide.
III) Blue : 5-Chloro-2-methoxy-N-
phenylethylbenzamide
IV) Yellow : 5-Chloro-2-hydroxy-N-benzylbenzamide
(
Abstract.pdf
12

ACCEPTED MANUSCRIPT
Highlights
•
5-Chloro-2-methoxy-N-phenylbenzamide and its
derivatives were synthesized.
•
•
The absolute configurations were defined.
Infrared spectroscopy indicates the presence of the
trans group configurations.
•
•
The redistributions of the charges were investigated
by UV-Vis spectroscopy.
Total dipole moments were obtained by molecular
modeling.
13