Crystal and molecular structure studies of (Z)-N-methyl-C-4-substituted phenyl nitrones by XRD, DFT, FTIR and NMR methods

Article abstract of DOI:10.1016/j.molstruc.2016.08.058

(Z)-N-methyl-C-4-substituted phenyl nitrones ^–O⁺N(Me)=C(H)R (Z-2a R = 4-ClC₆H₄, Z-2b R = 4-NO₂C₆H₄, Z-2c R = 4-CH₃OC₆H₄) were synthesized and cha

Full text of DOI:10.1016/j.molstruc.2016.08.058

Accepted Manuscript
Crystal and molecular structure studies of (Z)-N-methyl-C-4-substituted phenyl
nitrones by XRD, DFT, FTIR and NMR methods
Jamal Lasri, Naser Eltaher Eltayeb, Matti Haukka, Yousef Alghamdi
PII:
S0022-2860(16)30888-2
10.1016/j.molstruc.2016.08.058
MOLSTR 22884
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 11 June 2016
Revised Date: 17 August 2016
Accepted Date: 18 August 2016
Please cite this article as: J. Lasri, N.E. Eltayeb, M. Haukka, Y. Alghamdi, Crystal and molecular
structure studies of (Z)-N-methyl-C-4-substituted phenyl nitrones by XRD, DFT, FTIR and NMR
methods, Journal of Molecular Structure (2016), doi: 10.1016/j.molstruc.2016.08.058.
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ACCEPTED MANUSCRIPT
Crystal and molecular structure studies of (Z)-N-methyl-C-4-substituted
phenyl nitrones by XRD, DFT, FTIR and NMR methods
Jamal Lasri*, Naser Eltaher Eltayeb, Matti Haukka, Yousef Alghamdi
GRAPHICAL ABSTRACT
New N-methyl-C-4-substituted phenyl nitrones have been synthesized and characterized by
elemental analyses, FTIR, NMR and X-ray diffraction. The relative stabilities of their two
possible isomers (E and Z) have been investigated using the B3LYP/6-311++G(d,p).

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Crystal and molecular structure studies of (Z)-N-methyl-C-4-substituted
phenyl nitrones by XRD, DFT, FTIR and NMR methods
Jamal Lasria,*, Naser Eltaher Eltayeba, Matti Haukkab, Yousef Alghamdia
a
Department of Chemistry, Rabigh College of Science and Arts, P.O. Box 344, King
Abdulaziz University, Jeddah, Saudi Arabia
b University of Jyväskylä, Department of Chemistry, P.O. Box 35, FI-40014 University of
Jyväskylä, Finland
* Corresponding author at: Department of Chemistry, Rabigh College of Science and
Arts, P.O. Box 344, King Abdulaziz University, Jeddah, Saudi Arabia. E-mail address:
jlasri@kau.edu.sa (J. Lasri).
ABSTRACT
(Z)-N-methyl-C-4-substituted phenyl nitrones –O+N(Me)=C(H)R (Z-2a R = 4-ClC6H4, Z-
2b R = 4-NO2C6H4, Z-2c R = 4-CH3OC6H4) were synthesized and characterized by
1
13
elemental analyses, FTIR, H, C and DEPT-135 NMR spectroscopy and also by single
crystal X-ray diffraction (in the case of Z-2a and Z-2b). The geometries of the nitrone
molecules Z-2a, Z-2b and Z-2c and their E-isomers; (E)-N-methyl-C-4-chlorophenyl
nitrone E-2a, (E)-N-methyl-C-4-nitrophenyl nitrone E-2b and (E)-N-methyl-C-4-
methoxyphenyl nitrone E-2c were optimized using density functional theory (DFT) at the
B3LYP/6-311++G(d,p) level of theory. The theoretical vibrational frequencies obtained
by DFT calculations are in good agreement with the experimental values. The electronics
structures were described in terms of the distribution of the highest occupied molecular
orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). Gauge
independent atomic orbital (GIAO) method was used to calculate the NMR spectra, the
correlation between the calculated and experimental chemical shifts is mostly in the range
1
of 0.94-0.97 for H, whereas, the correlation for 13C is 0.99. Thermodynamics study
showed that the Z-isomer is favoured than E-isomer with energy barrier of 7.1, 7.2 and

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7.1 Kcal/mol for Z-2a, Z-2b and Z-2c, respectively. The abundance of the most stable
species Z-isomers is equal to 99.99% for all three compounds at 298 K in gas phase.
Keywords: (Z)-N-methyl-C-4-substituted phenyl nitrones; Single crystal X-ray; NMR;
DFT; B3LYP.
1. Introduction
Acyclic and cyclic nitrones have been extensively reviewed in organic chemistry [1,2],
they have been utilized for the preparation of numerous natural products with interesting
biological activities [3]. These products are found to act as an important key step in the
incorporation of multiple stereo-centers via 1,3-dipolar cycloaddition reactions [4]. On
this regards, nitrone moiety is found to possess pharmacological applications [5] and
form an important part of the molecular structure of many drugs. Some nitrones have
biological activities in several animal models [6,7]. Ageing, Alzheimer and Parkinsons
diseases as well as cancer development are very known to have improved levels of free
radicals and oxidative stress. Furthermore, nitrones have also anticancer activities in
various experimental cancer models and have potential as therapeutics in various cancers
[8]. On the other hand, the combination of antioxidants with nitrones has shown a
synergistic effect to inhibit the acute acoustic noise induced hearing loss [9]. Nitrone
compounds are also of industrial importance in the corrosion of metals / alloys in acidic
media (organic) as most carboxylic acids are utilized as building blocks in a variety of
industrial processes such as drugs, fibers and plastics [10-13].
–
In this work, (Z)-N-methyl-C-4-substituted phenyl nitrones O+N(Me)=C(H)R (Z-2a R =
4-ClC6H4, Z-2b R = 4-NO2C6H4, Z-2c R = 4-CH3OC6H4) were synthesized and
1
characterized by elemental analyses, FTIR, H, 13C and DEPT-135 NMR spectroscopy
and also by single crystal X-ray diffraction (in the case of Z-2a and Z-2b). Moreover, we
were interested to look for the correlations between the experimental results and the
computational calculations based on density functional theory (DFT) of electronic,
spectroscopic properties.
2. Experimental Section

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2.1. Material and instrumentation
Solvents and reagents were obtained from commercial sources (Aldrich) and used as
received. C, H and N elemental analyses were carried out by the Microanalytical Service
of the King Abdulaziz University. 1H, 13C and DEPT-135 NMR spectra (in CDCl3) were
measured on Bruker Avance III HD 600 MHz (AscendTM Magnet) spectrometer at
1
ambient temperature. H, 13C and DEPT-135 chemical shifts (δ) are expressed in ppm
relative to TMS. Infrared spectra (400-4000 cm-1) were recorded on an Alpha Bruker FT-
IR instrument in KBr pellets.
2.2. Synthesis of (Z)–N-methyl-C-4-substituted phenyl nitrone Z-2a, Z-2b and Z-2c
To a solution of N-methylhydroxylamine hydrochloride (1.00 g, 11.97 mmol) in MeOH
(4 mL) was added sodium carbonate (0.63 g, 5.98 mmol). The reaction mixture was
stirred at room temperature for 5 min. 4-Chlorobenzaldehyde 1a (1.53 g, 10.88 mmol), 4-
nitrobenzaldehyde 1b (1.64 g, 10.88 mmol) or 4-metoxybenzaldehyde 1c (1.48 g, 10.88
mmol) was added and the reaction mixture was stirred for 12 h. The precipitate formed
was then filtered off and the filtrate was evaporated in vacuo. The solid was then
dissolved in CHCl3 resulting in the precipitation of NaCl, and it was filtered off and the
CHCl3 was then removed in vacuo. The final product was washed with Et2O to afford the
pure (Z)-N-methyl-C-4-chlorophenyl nitrone Z-2a, (Z)-N-methyl-C-4-nitrophenyl nitrone
Z-2b or (Z)-N-methyl-C-4-methoxyphenyl nitrone Z-2c, respectively, in ca. 90% yield
(Scheme 1).

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R
_
O
O
Na2CO3
+
+
MeNHOH.HCl
C
N
R
C
MeOH
r.t., 12 h
Me
H
H
Z-2a: R = Cl
1a: R = Cl
Z-2b: R = NO2
Z-2c: R = CH3O
1b: R = NO2
1c: R = CH3O
Scheme 1. Synthesis of N-methyl-C-4-substituted phenyl nitrones Z-2a, Z-2b and Z-2c.
–O+N(Me)=C(H)(4-ClC6H4) (Z-2a)
1
Yield: 91%. IR (cm-1): 1655 (C=N). H NMR (CDCl3), δ: 3.77 (s, 3H, CH3N), 7.28 (s,
1H, C(H)=N), 7.28 (d, 2H, JHH = 8.6 Hz, CHar), 8.09 (d, 2H, JHH = 8.6 Hz, CHar). 13C
NMR (CDCl3), δ: 54.4 (CH3N), 128.6 (CHaromatic), 128.9 (Caromatic), 129.5 (CHaromatic),
134.0 (C(H)=N), 135.6 (Caromatic). DEPT-135 NMR (CDCl3), δ: 54.4 (CH3N), 128.6
(CHaromatic), 129.5 (CHaromatic), 134.0 (C(H)=N). Anal. Calc. for C8H8NOCl: C, 56.65; H,
4.75; N, 8.26. Found: C, 56.77; H, 4.91; N, 8.15%.
–O+N(Me)=C(H)(4-NO2C6H4) (Z-2b)
1
Yield: 90%. IR (cm-1): 1598 (C=N). H NMR (CDCl3), δ: 3.98 (s, 3H, CH3N), 7.54 (s,
1H, C(H)=N), 8.28 (d, 2H, JHH = 8.8 Hz, CHar), 8.40 (d, 2H, JHH = 8.8 Hz, CHar). 13C
NMR (CDCl3), δ: 55.1 (CH3N), 123.8 (CHaromatic), 128.7 (CHaromatic), 133.1 (C(H)=N),
136.0 (Caromatic), 147.9 (Caromatic). DEPT-135 NMR (CDCl3), δ: 55.1 (CH3N), 123.8
(CHaromatic), 128.7 (CHaromatic), 133.1 (C(H)=N). Anal. Calc. for C8H8N2O3: C, 53.33; H,
4.48; N, 15.55. Found: C, 53.48; H, 4.17; N, 15.30%.

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–O+N(Me)=C(H)(4-CH3OC6H4) (Z-2c)
1
Yield: 89%. IR (cm-1): 1603 (C=N). H NMR (CDCl3), δ: 3.75 (s, 3H, CH3O), 3.76 (s,
3H, CH3N), 6.86 (d, 2H, JHH = 8.9 Hz, CHar), 7.25 (s, 1H, C(H)=N), 8.14 (d, 2H, JHH
=
8.9 Hz, CHar). 13C NMR (CDCl3), δ: 53.8 (CH3O), 55.3 (CH3N), 113.8 (CHaromatic), 123.4
(Caromatic), 130.5 (CHaromatic), 135.2 (C(H)=N), 161.1 (Caromatic). DEPT-135 NMR (CDCl3),
δ: 53.8 (CH3O), 55.3 (CH3N), 113.8 (CHaromatic), 130.5 (CHaromatic), 135.2 (C(H)=N).
Anal. Calc. for C9H11NO2: C, 65.44; H, 6.71; N, 8.48. Found: C, 65.56; H, 6.88; N,
8.35%.
2.3. X-ray crystallography
For the X-ray structure determinations; X-ray-quality single crystal of (Z)-N-methyl-C-4-
chlorophenyl nitrone Z-2a and (Z)-N-methyl-C-4-nitrophenyl nitrone Z-2b was obtained
by slow evaporation from chloroform. The crystals of Z-2a and Z-2b were immersed in
cryo-oil, mounted in a MiTeGen loop and measured at 120–170 K. The X-ray diffraction
data were collected on a Bruker KappaApex II or an Agilent Technologies Supernova
using Mo Kα radiation (λ = 0.70173 Å). The Denso/Scalepack [14] or CrysAlisPro [15]
program packages were used for cell refinements and data reductions. The structures
were solved by charge flipping method using the SUPERFLIP [16] program. A multi-
scan absorption correction based on equivalent reflections (SADABS, [17] CrysAlisPro)
was applied to all data. Structural refinements were carried out using SHELXL2014 [18].
The hydrogen atoms were positioned geometrically and constrained to ride on their
parent atoms, with C–H = 0.95–0.98 Å and Uiso = 1.2–1.5 Ueq (parent atom). The
crystallographic details are summarized in Table 1. CCDC numbers 1482396 and
1482397 contain the supplementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.

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Table 1. Crystal Data.
Z-2a
Z-2b
C8H8ClNO
169.60
170(2)
C8H8N2O3
180.16
120(2)
Empirical formula
Fw
Temp (K)
0.71073
Monoclinic
P21/c
0.71073
Orthorhombic
Pbc21
λ
(Å)
Cryst syst
Space group
a (Å)
11.6636(5)
9.7903(4)
7.3574(3)
107.602(2)
800.81(6)
4
11.70106(16)
10.94074(16)
2.3169(2)
90
b (Å)
c (Å)
β
(deg)
V (Å3)
1576.78(4)
8
Z
calc (Mg/m3)
(Mo K
) (mm-1)
1.407
1.518
ρ
0.413
0.119
µ
α
11951
38660
No. reflns.
Unique reflns.
GOOF (F2)
Rint
2363
5981
1.145
1.120
0.0504
0.0582
0.0951
0.0287
0.0350
0.1027
R1a (I
wR2b (I
≥
2
σ
)
≥
2σ)
2 2
a R1 =
Σ
||Fo| – |Fc||/
Σ
|Fo|. b wR2 = [ [w(Fo2 – Fc2)2]/ [w(Fo ) ]]1/2
Σ Σ .

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2.4. Computational methods
Molecular electronic structure calculations were performed using the density functional
theory (DFT). The DFT calculations were performed by Becke's three- parameter
exchange functional with Lee–Yang–Parr (LYP) correlation functional. Gaussian 09
software [19] were used to performed full geometry optimizations of the compounds at
the B3LYP level of theory using an 6-311++G (d,p) basis set. The optimization was
confirmed with absence of negative frequency. The gauge-independent atomic orbital
(GIAO) method was used at the B3LYP/6-311++G (d,p) level of theory to calculate the
NMR chemical shifts with Polarizable Continuum Model (PCM). The softwares;
Chemcraft [20] and Veda 4 [21] were used to analysis of Gaussian 09 output files.
3. Results and discussion
In this work, the molecular structure of (Z)-N-methyl-C-4-chlorophenyl nitrone Z-2a, (Z)-
N-methyl-C-4-nitrophenyl nitrone Z-2b and (Z)-N-methyl-C-4-methoxyphenyl nitrone Z-
2c have been studied theoretically by DFT and experimentally by XRD, FTIR and NMR
methods. The E-isomers; (E)-N-methyl-C-4-chlorophenyl nitrone E-2a, (E)-N-methyl-C-
4-nitrophenyl nitrone E-2b and (E)-N-methyl-C-4-methoxyphenyl nitrone E-2c have
been studied theoretically using DFT method.
3.1. Crystal structure
The molecular structure and numbering of (Z)–N-methyl-C-4-chlorophenyl nitrone Z-2a
and (Z)–N-methyl-C-4-nitrophenyl nitrone Z-2b are shown in Fig. 1 and Fig. 2, and the
crystal packing along the b axis is presented in Fig. 3 and Fig. 4, respectively. Table 1
showed crystal data and structure refinement for compounds Z-2a and Z-2b. Table 2 lists
some selected bond lengths, bond angles and selected torsion angles.
Crystal structure of (Z)–N-methyl-C-4-chlorophenyl nitrone Z-2a

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In the (Z)-N-methyl-C-4-chlorophenyl nitrone Z-2a, the benzene ring is planar. The
chloride atom, Cl1, deviates from this plane by 0.010 (1) Å while the methyl C atom, C7,
is out of the plane by 0.031 (2) Å. The chains O1/N1/C7/C1 and C8/N1/C7/C1 have
torsional angles −2.0 (3)° and 176.81 (19)°, respectively. The bond lengths indicate
double-bond character for the C7=N1 [1.306 Å] bond and single-bond character for the
C8—N1 [1.474 Å] and O1—N1 [1.294 Å] bonds. An intramolecular C(6)—H(6)···O1
hydrogen bond is observed (Fig. 1). This interaction generates an S(6) ring motif.
In the crystal, molecules are linked through intermolecular C8—H8···O1 [symmetry
code: 1−x,1/2+y,3/2−z] and C7—H7···O1 [x,1/2 − y,-1/2 + z] hydrogen bonds into
supramolecular chains propagating along the b axis direction (Fig. 3). C—H···π
interactions are present C(5)—H(5)··· Cg(1) [symmetry code: (X,1/2-Y,1/2+Z)] and
C(8)—H(8B)···Cg(1) [symmetry code: 1-X,1-Y,2-Z], with H.·Cg 2.73 Å and 2.75 Å,
respectively. Where Cg(1) is the centroid of the ring represented by C(1)—C(6).
Crystal structure of (Z)–N-methyl-C-4-nitrophenyl nitrone Z-2b
In the (Z)-N-methyl-C-4-nitrophenyl nitrone Z-2b, the benzene ring is planar. The
nitrogen atom, N2, deviates from this plane by 0.014(1) Å [0.011(1) Å in molecule B],
while the methyl C atom, C8, is out of the plane by 0.069(2) Å [-0.026(2) Å in molecule
B]. The chains O1/N1/C7/C6 and C8/N1/C7/C6 have torsional angles 0.7(3)° [-1.0(2) in
molecule B] and -179.73(15)° [-179.75(14) in molecule B], respectively. The bond
lengths indicate double-bond character for the C7=N1 [1.311 Å] bond and single-bond
character for the C8—N1 [1.475 Å] and O1—N1 [1.290 Å] bonds as same as for
molecule B.
An intramolecular C(5)—H(5)···O1 hydrogen bond is observed in molecule A and B
(Fig. 2). This interaction generates an S(6) ring motif. In the crystal, molecules are linked
through intermolecular C7—H7A…O1 [symmetry code: 1-x,1/2+y,z], C2—H2A…O3
[symmetry code: -x,1/2+y,z] and C4—H4A…O2 [symmetry code: -x,-1/2+y,z] for
molecule A and C7B—H7BA…O1B [symmetry code: -x,-1/2+y,z], C2B—H2BA…O3B
[symmetry code: 1-x,-1/2+y,z] and C4B—H4BA…O2B [symmetry code: 1-x,1/2+y,z]

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for molecule B, hydrogen bonds into supramolecular sheets propagating along the b axis
direction (Fig. 4). C—H···π interaction is absent and the shortest centroid–centroid
separations being 4.004 Å for aromatic π–π stacking between Cg(1)-Cg(2) [symmetry
code: X,Y,Z], Where Cg(1) is the centroid of the ring represented by C(1)—C(6) and
Cg(2) is the centroid of the ring represented by C(1B)—C(6B).
Fig. 1. ORTEP drawing of (Z)-N-methyl-C-4-chlorophenyl nitrone Z-2a showing the
atom numbering scheme and 30% probability displacement ellipsoids of non-H atoms.

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Fig. 2. ORTEP drawing of (Z)-N-methyl-C-4-nitrophenyl nitrone Z-2b showing the atom
numbering scheme and 30% probability displacement ellipsoids of non-H atoms.

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Fig. 3. Packing diagram for (Z)-N-methyl-C-4-chlorophenyl nitrone Z-2a, viewed down
the b axis.
Fig. 4. Packing diagram for (Z)-N-methyl-C-4-nitrophenyl nitrone Z-2b, viewed down
the b axis.
3.2. Computational study
3.2.1. Geometry optimization
The structures of Z/E 4-substituted phenyl nitrones Z-2a, E-2a, Z-2b, E-2b, Z-2c and E-
2c were optimized using DFT at the B3LYP/6-311++G(d,p) level of theory. Selected
bond lengths, bond and torsion angles of the experimental and calculated data (gas-
phase), DFT (B3LYP/6-311++G(d,p)), are shown in in Table 2. It is showed that
obtained optimized parameters have a good correlation with X-ray results. All bonds
lengths as similar as experimental data for Z-2a and Z-2b. However, H-C bonds in
optimized structure are longer than that in crystal structure (longer by 0.13 Å). In Z-2a,
the most notable inconsistency occurs at C-N-C-C torsion angle (176.85° for X-ray,
179.99° for DFT) and O-N-C-C torsion angle (-0.01° for X-ray, -2.04° for DFT). In Z-2b,
the most notable inconsistency occurs at C-N-C-C torsion angle (-179.77° for X-ray,
0.00° for DFT) and O-N-C-C torsion angle (-1.016° for X-ray, 0.01° for DFT). All of

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these torsion angles are partially involved in the hydrogen bond. It can be considered that
intermolecular interaction affects the crystal system [22]. Comparing the structural
parameters for the three pairs of isomers showed that there are a difference in torsion
angles C-N-C-C and O-N-C-C for Z-2a, E-2a, Z-2b, E-2b, Z-2c and E-2c about 6.0° and
4.0°, respectively. This difference attributed to the twisting of E-isomers.
Table 2. Selected structural parameters for Z/E-isomers
Atomic
Z-2a
E-2a
Exper. Z-2b
E-2b Exper.
Z-2c
E-2c
numbering
C(C6H4)-C 1.45
1.46
1.45
1.45
1.45
1.45
1.45
1.46
(Ǻ)
C-H (Ǻ)
C-N (Ǻ)
N-O (Ǻ)
1.08
1.32
1.28
1.08
1.32
1.28
1.48
0.95
1.31
1.29
1.47
1.08
1.32
1.27
1.48
1.08
1.32
1.27
1.48
0.95
1.31
1.29
1.47
1.08
1.32
1.28
1.48
1.08
1.31
1.28
1.48
N-C (CH3) 1.48
(Ǻ)
C-N-C-C
(°)
179.99 -6.49
176.85 0.00
-6.74
-179.77 179.99 -6.54
O-N-C-C
(°)
-0.01
175.87
-2.04
0.01
175.93 -1.016
0.00
175.61
3.2.2 Vibrational and potential energy distribution (PED) analysis
The assignment of the fundamental vibrations of the optimized ground state geometry of
Z-2a, Z-2b and Z-2c reported at the B3LYP/6-311++G(d,p) level using Gaussian 09
program. Vibration frequencies calculated at B3LYP/6-311++G(d,p) level were scaled by
0.9679, which is a typical scaled factor for the calculated method [23]. The detailed

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descriptions of the assignment have been shown in Table 3, Table S1 and Table S2
(Supplementary Information). Veda 4 software [21] was used to assign the calculated
frequencies. The predicted vibration frequencies and the experimental data are very close
to each other. In conclusion, the scaled frequencies of the DFT calculation are in good
agreement with the corresponding FTIR vibration.
Table 3. Computational calculated vibrational wavenumbers (harmonic frequency (cm-
1)), assignments and contribution for (Z)-N-methyl-C-4-chlorophenyl nitrone Z-2a at
DFT/B3LYP utilizing 6-311++G (d,p) basis sets.
PED (%)
Frequencies
Experimental
DFT
3183
3085
3134
3105
3100
3096
3064
3052
3041
2961
1580
1573
υ CH 97
υ CH 96
υ CH 94
υ CH 97
υ CH 95
υ CH -17
υ CH -50
υ CH 33
υ NC 47
υ CC 25
3038
3038
υ CH -16 υ CH 65
υ CH 50
υ CH 33
2946
1595
1556
υ CH 33
β
CCC -
10
υ CC -11
υ CC 10
1485
1538
υ CC -24
υ CC 23

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1427
1427
1467
1455
1420
1413
1387
1381
β HCC 15 β HCC 14 β HCC -
13
β HCC 14 β HCH 12 β HCH -
24
β HCH τ HCNC τ HCNC -10
12
10
β HCH -39 β HCH 39 τ HCNC
13
1405
υ ON 22
β HCC 25
β HCH
25
β HCH -18 β HCH -
11
β HCH -
17
υ CC 10
υ CC -15
β HCC -
12
1310
1257
1297
1279
υ CC 10
υ CC -14
υ CC 20 β HCC 10
β HCC 17
υ CC 19 β HCC 11 β HCC -
10
β HCC 16
1208
υ CC -16
υ CC 27
β CCC -
12
1162
1166
1157
υ ON -10 β HCC 12 β HCC 24
υ ON 35
υ CC -11
β HCH 16
υ NC -11
β HCC -
13
β HCC -10
1101
1100
υ CC 10
β HCC -
14
β HCC β HCC -
21 12
β HCC -12
1090
β HCH - τ HCNC -
16 52

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1068
β HCH -10
τ HCNC
20
τ HCNC -
20
1062
992
υ CC 16
υ CC 18 υ ClC -12
τ HCNC 10
1013
950
β CCC -41
β CCC -
22
β CCC 19
967
941
933
840
830
811
768
708
693
625
τ HCCC 54
υ ON 19
τ HCCC
27
τ CCCC
10
υ NC 36
β NCC -
11
τ HCCC 25 τ HCCC -
41
τ CCCC
13
856
υ CC -17
υ CC -12
β CCC -
18
τ HCCC -
30
τ HCCC
42
τ HCCC -
14
τ HCCC
38
τ HCCC
30
τ HCCC 62
τ HCCC
12
706
τ CCCC -
18
τ CCCC - γ CCCC -
28
17
υ NC -13
υ ClC -19
β CCC -
17
630
β CCC -12
β CCC -
20
β CCC 33

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581
557
492
449
409
363
344
γ OCCN -
59
υ NC 16
υ ClC -13
β ONC
37
τ HCCC 11 γ OCCN
16
γ ClCC -
18
γ CCCC 30
υ ClC 30 β ONC 29 β CNC -
11
τ HCCC 12 τ CCCC - τ CCCC -
τ CCCC 16
37
24
β CCC -30 β CNC 18
β ClCC
26
τ CCCC 22 τ CNCC - γ ClCC -
17 29
293
263
187
υ CC 15
υ ClC 14 β CCC 14
β CNC 25
β NCC 23 β ClCC 41
τ HCNC 20
τ CNCC
22
γ ClCC -
25
142
136
79
τ HCNC 25 τ HCNC
25
τ CNCC -
17
β NCC -28 β CCC 38
β ClCC
12
τ NCCC 59
τ CNCC
22

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61
τ NCCC -
13
τ CCCC -
14
τ CCCC
25
τ CNCC
13
γ CCCC -20
υ – stretching; γ – out-of-plane deformation; τ – torsion; β – bending.
Aromatic C–H vibrations
Weak bands in the region 3100–3000cm−1 in aromatic compounds are assigned to
aromatic C–H stretching vibrations [24]. For the compound Z-2a, the C–H stretching
vibrations are found at 3080 (m) and 3036 (m) [DFT: 3134-3064 cm-1], for the compound
Z-2b, the C–H stretching vibrations are found at 3080 (w) [DFT: 3121-3080 cm-1], For
the compound Z-2c, the C–H stretching vibrations are overlap with water broad bands
[DFT: 3129-3091 cm-1], The theoretically computed C–H vibrations shows good
agreement with recorded spectrum as well as the literature data [24].
The presence in the IR spectra of a strong band ν C–H near 3100 cm-1 is a characteristic
feature of cyclic aldo-nitrones [25]. This peak appeared at 3185 cm-1 [DFT: 3105 cm-1]
and 3112 cm-1 [DFT: 3095 cm-1] for compounds Z-2a and Z-2b, respectively. This peak
is overlapped with water broad bands [DFT: 3101 cm-1] in compound Z-2c.
C–C vibrations
The ring stretching vibrations of benzene and their derivatives are highly characteristic of
the aromatic ring itself. The bands between 1400 and 1650 cm-1 in benzene derivatives
are usually assigned to C–C stretching modes [26]. For the compound Z-2a, the C–C
stretching vibrations are found at 1592 (s), 1555 (s), and 1484 (s) [DFT: 1573 and 1538
cm-1], for the compound Z-2b, the C–C stretching vibrations are found at 1598 (s), 1577
(m), and 1510 (s) [DFT: 1583, 1579, 1553 and 1517 cm-1], for the compound Z-2c, the
C–C stretching vibrations are found at 1603 (s), 1569 (s), 1509 (s) and 1414 (s) cm-1
[DFT: 1593, 1583,1544 and 1400 cm-1], the mean difference between theoretical
(B3LYP/6-311++G(d,p)) and experimental frequencies are acceptable. It shows the good
agreement between theoretical and experimental C–C stretching vibrations.

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Methyl group (C–H) vibrations
The C–H methyl group stretching vibrations are generally observed in the range 3000–
2800cm−1 [26]. In the compound Z-2a, the bands with medium peaks assigned for the
CH3 stretching vibrations are found at 2944 (m) cm-1 [DFT: 3059 cm-1], for the
compound Z-2b, the C–H stretching vibrations are found at 3012 (m) cm-1 [DFT: 3063
cm-1], for the compound Z-2c, the C–H stretching vibrations are found at 2946 (s) cm-1
[DFT: 3055 cm-1]. The theoretical calculations overestimate the experimental data by
about 3%. In addition to methyl group, the compound Z-2c has a methoxy group (OCH3),
the C–H of methoxy appeared at 2841 cm-1 [DFT: 3008 cm-1].
C–N and O–N vibrations
The C–N and O–N stretching vibrations are the main characteristic IR bands of a nitrone
molecule and occur at about 1520–1590 and 1200–1350 cm−1, respectively [27]. The C–
N and O–N stretching for the compound Z-2a are found at 1592 (s) and 1308 (s),
respectively [DFT: 1580 and 1413 cm-1, respectively], for the compound Z-2b, the C–N
and O–N stretching vibrations are found at 1598 (s) and 1341 cm-1 (s), respectively
[DFT: 1553 and 1316 cm-1, respectively], for the compound Z-2c, the C–N and O–N
stretching vibrations are found at 1603 (s) and 1341 cm-1 (s), respectively [DFT: 1593
and 1411 cm-1, respectively]. The mean difference between theoretical (B3LYP/6-
311++G(d,p)) and experimental frequencies are acceptable. It shows the good agreement
between theoretical and experimental C–N and O–N stretching vibrations.
In conclusion, the theoretical calculation of vibrations frequencies at B3LYP/6-311++G
(d,p) method approximately coincides with observed values of FTIR and these
assignments are in good agreement with the literature data [24-27].
3.2.3. NMR Analysis

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13
The 1H and C NMR spectra of the (Z)–N-methyl-C-4-substituted phenyl nitrones Z-2a,
Z-2b and Z-2c were recorded experimentally in deuterated chloroform (CDCl3) as well as
they have been calculated using DFT/B3LYP/6-311++G(d, p) level of theory with GIAO
1
approach in chloroform. The chemical shifts for H and 13C nuclei in solution and
theoretical values are collected and reported in Table 4. Chemical shifts in the 1H and 13C
NMR spectra were assigned with the help of DFT calculations of shielding constants. The
obtained shielding constants were recalculated into theoretical chemical shifts. For this
purpose the TMS shielding constants were calculated at the same level of theory as for
acyclic nitrones Z-2a, Z-2b and Z-2c. The theoretically calculated chemical shifts were in
1
good agreement with the experimental ones, and the correlation coefficients for H were
0.9643 (Z-2a), 0.9424 (Z-2b) and 0.971 (Z-2c). The correlation coefficients for 13C were
0.9903 (Z-2a), 0.9966 (Z-2b) and 0.9957 (Z-2c) (Fig. S1). The effect of the electron
withdrawing chloro and nitro groups and the electron donating methoxy group on
chemical shifts can be seen in quaternary carbon C-9 of the phenyl ring, with
experimental chemical shifts of 135.6, 147.9 and 161.1 ppm in Z-2a, Z-2b and Z-2c,
respectively. This trend also observed in theoretical results.
Table 4. Comparison of the calculated chemical shifts (GIAO
B3LYP/6-311++G(d,p)) with experimental in CDCl3.
Z-2a
Z-2b
Z-2c
DFT-
TMS
DFT-
TMS
DFT-
TMS
Atom
H-4
Exp
7.28
8.09
7.28
7.28
7.28
Exp
7.54
8.4
Exp
7.25
8.14
6.86
6.86
6.86
7.61
9.81
7.69
7.59
7.38
7.81
9.84
8.66
8.54
7.48
7.49
9.87
7.03
7.20
7.36
H-6
H-8
8.4
H-11
H-13
8.28
8.28

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H-15
H-16
H-17
H
3.77
3.77
3.98
3.86
3.75
3.75
3.75
3.76
3.76
3.76
3.71
3.71
3.59
3.83
3.83
4.15
3.77
3.77
3.98
3.86
3.77
3.67
3.98
3.80
-
-
-
-
-
-
-
-
-
-
-
-
H
H
C-2
C-3
129.5
134
137.6
142.6
134.9
135.8
151.3
134.9
137.4
57.8
136
133.1
128.7
123.8
147.9
123.8
128.7
55.1
145.7
142.7
133.0
132.7
155.4
130.9
136.0
58.9
123.4
135.2
130.5
113.8
161.1
113.8
130.5
53.8
131.5
142.8
136.2
114.2
170.2
123.6
138.3
57.0
C-5
128.6
128.9
135.6
128.9
128.6
54.4
-
C-7
C-9
C-10
C-12
C-14
C-15
-
-
-
55.3
57.7
3.2.4. Thermodynamic study
Z- and E-isomers of the three compounds were studied using theoretical calculation to
evaluate the energetic difference between both isomers and the relative importance of the
intramolecular hydrogen bonds. Thermodynamics study showed that the Z-isomer is
favoured than E-isomer with energy barrier of 7.1, 7.2 and 7.1 Kcal/mol for Z-2a, Z-2b
and Z-2c, respectively, this value is consistence with breaking of intramolecular H bond
N—O···H. The relative abundances of the Z- and E-isomers were calculated using Gibbs
free energy equation; ∆G = -RTlnK (where ∆G denotes the difference between the Gibbs

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free energies of E-isomer relative to the Z-isomer and K is the corresponding equilibrium
constant). The abundance of the most stable species, Z is equal to 99.99% for all three
compounds at 298 K in gas phase. This indicates that the Z-isomer is the predominant in
the gas phase. These results are in good agreement with the experimentally measured X-
ray structure and NMR spectra which showed a pure single Z-isomer as well as in
agreement with the literature [28].
3.2.5. Molecular Orbital analysis
Frontier molecular orbitals (FMOs) play crucial role in the chemical stability of a
molecule and in the interactions between atoms. They are considered to be effective in
determining the characteristics of the molecules such as optical properties and biological
activities. Among these, the highest occupied molecular orbital (HOMO) and the lowest
unoccupied molecular orbital (LUMO) are the most important. The HOMO represents the
ability of a molecule to donate an electron, while the LUMO is an electron acceptor. Fig.
5, Fig. S2 and Fig. S3 (Supplementary Information) show the electron density in HOMO
and LUMO molecular orbitals. In (Z)–N-methyl-C-4-chlorophenyl nitrone Z-2a and (E)–
N-methyl-C-4-chlorophenyl nitrone E-2a, the HOMO and LUMO orbitals were mainly
delocalized over the molecule with high electron density on nitrogen atoms in HOMO
which reduced in LUMO suggesting n-π* transition, HOMO showed π-bonding over
whole molecule, whereas LUMO showed π*-antibonding on the molecule, suggesting π -
π*, therefore, the transitions from HOMO to LUMO are mixture of π -π* and n-π*.
Z-2a
E-2a

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Fig. 5. Molecular orbital (HOMO down and LUMO up) shapes of Z-2a and E-2a using
B3LYP/6-311++G (d,p).
3.2.6. Molecular electrostatic potential
Molecular electrostatic potential (MEP) is used for investigating the chemical reactivity
of a molecule, the surfaces of Z-2a, E-2a, Z-2b, E-2b, Z-2c and E-2c were plotted over
an optimized electronic structures using B3LYP/6-311++G(d,p) as shown in Fig. 6. The
MEP is especially important for the identification of the reactive sites of nucleophilic or
electrophilic attack in hydrogen-bonding interactions and for the understanding of the
process of biological recognition. The most positive (blue) regions are localized on
hydrogen atoms of azomethine group (C(H)=N), showing electrophilic reactivity;
whereas the most negative (red) regions are observed around the oxygen atoms. The MEP

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map is supported by the intermolecular interactions, C8—H8···O1 [symmetry code:
1−x,1/2+y,3/2−z] and C7—H7···O1 [x,1/2 − y,-1/2 + z] hydrogen bonds, which linked the
molecules into supramolecular chains propagating along the b axis direction (Fig. 3) for
compound Z-2a. The crystal structure of compound Z-2b also supported the MEP;
molecules are linked through intermolecular C7—H7A…O1 [symmetry code: 1-
x,1/2+y,z], C2—H2A…O3 [symmetry code: -x,1/2+y,z] and C4—H4A…O2 [symmetry
code: -x,-1/2+y,z].
-5.115 x10-2
5.115x10-2
-5.697 x10-2
5.697 x10-2
-5.450 x10-2
5.450 x10-2
-4.842 x10-2
4.842 x10-2
-5.972 x10-2
5.972 x10-2
-6.399 x10-2
6.399 x10-2

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Fig. 6. Molecular electrostatic potential map of Z-2a, E-2a, Z-2b, E-2b, Z-2c and E-2c
calculated at B3LYP/ 6-311++G(d,p) level.
Conclusions
In this work, (Z)-N-methyl-C-4-cholorophenyl nitrone Z-2a, (Z)-N-methyl-C-4-
nitrophenyl nitrone Z-2b and (Z)-N-methyl-C-4-methoxyphenyl nitrone Z-2c were
synthesized by treatment of 4-chlorobenzaldehyde, 4-nitrobenzaldehyde or 4-
methoxybenzaldehyde, respectively, with N-methylhydroxylamine and sodium carbonate.
The geometries of the Z-2a, Z-2b and Z-2c and their E-isomers; (E)-N-methyl-C-4-
chlorophenyl nitrone E-2a, (E)-N-methyl-C-4-nitrophenyl nitrone E-2b and (E)-N-
methyl-C-4-methoxyphenyl nitrone E-2c molecules were optimized using DFT at the
B3LYP/6-311++G(d,p) level of theory. The theoretical vibrational frequencies obtained
by DFT calculations are in good agreement with the experimental values. The electronics
structures were described in terms of the distribution of the HOMO and LUMO. GIAO
method was used to calculate the NMR spectra, the correlation between the calculated
1
and experimental chemical shifts is mostly in the range of 0.94-0.97 for H, whereas, the
correlation for 13C is 0.99. Thermodynamic study showed that the Z-isomer is favoured
than E-isomer with energy barrier of 7.1, 7.2 and 7.1 Kcal/mol for Z-2a, Z-2b and Z-2c,
respectively. The abundance of the most stable Z-isomers is equal to 99.99% for all three
compounds at 298 K in gas phase. MEP shows that the most positive (blue) regions are
localized on hydrogen atoms of azomethine group (C(H)=N), showing electrophilic
reactivity; whereas the most negative (red) regions are observed around the oxygen

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atoms. Moreover, these results are supported by crystal structure packing of compounds
Z-2a and Z-2b.
Acknowledgment
This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz
University, Jeddah, under grant no. (G-100-662-37). The authors, therefore, acknowledge
with thanks DSR for technical and financial support.
Appendix A. Supplementary material
Supplementary data associated with this article can be found, in the online version, at…
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Highlights
• Crystal structures of (Z)–N-methyl-C-4-substituted phenyl nitrones were descried.
• IR and NMR spectra of (Z)–N-methyl-C-4-substituted phenyl nitrones were studied.
• DFT calculations were used to assign the NMR chemical shifts.
• DFT calculations were used to analyze the molecular orbitals and molecular electrostatic
potential.
• Correlation between experimental and computational spectroscopy was evaluated.
• Thermodynamic study of isomerism was reported.