Spectroscopic studies of aryl substituted 1-phenyl-2-pyrazolines: Steric and electronic substitution effects

Article abstract of DOI:10.1016/j.molstruc.2018.07.052

A series of aryl substituted 1-phenyl-2-pyrazolines containing electron-donating and electron-withdrawing substituents on different positions of the C₃– or C₅-aryl groups were synthesized and their steric and electronic effects on ch

Full text of DOI:10.1016/j.molstruc.2018.07.052

Accepted Manuscript
Spectroscopic studies of aryl substituted 1-phenyl-2-pyrazolines: Steric and electronic
substitution effects
Marzieh Soltani, Hamid R. Memarian, Hassan Sabzyan
PII:
S0022-2860(18)30871-8
10.1016/j.molstruc.2018.07.052
MOLSTR 25457
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 28 May 2018
Revised Date: 14 July 2018
Accepted Date: 16 July 2018
Please cite this article as: M. Soltani, H.R. Memarian, H. Sabzyan, Spectroscopic studies of aryl
substituted 1-phenyl-2-pyrazolines: Steric and electronic substitution effects, Journal of Molecular
Structure (2018), doi: 10.1016/j.molstruc.2018.07.052.
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ACCEPTED MANUSCRIPT
Graphical Abstract
σ- or π-donor/acceptor ability effects of the C3- and C5-aryl substitutions on the UV-
Vis, IR and NMR spectral data in 2-pyrazolines were investigated experimentally and
theoretically. Marzieh Soltani, Hamid R. Memarian and Hassan Sabzyan.

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Spectroscopic studies of aryl substituted 1-phenyl-2-pyrazolines:
steric and electronic substitution effects
Marzieh Soltani, Hamid R. Memarian* and Hassan Sabzyan*
Department of Chemistry, University of Isfahan, 81746-73441 Isfahan, I. R. Iran.
Abstract. A series of aryl substituted 1-phenyl-2-pyrazolines containing electron-donating
and electron-withdrawing substituents on different positions of the C3- or C5-aryl groups were
synthesized and their steric and electronic effects on characteristic spectral data were
investigated by experimental spectroscopic methods (UV-Vis, IR and NMR) and DFT
computations. Whereas the C5-aryl group of the heterocyclic ring behaves as σ-
donor/acceptor substituent, the π-donor/acceptor ability of the C3-aryl group depends on the
co-planarity of the substituent with the aryl ring and also the extent of the orientation of this
C3-aryl ring towards the C=N double bond of the heterocyclic ring. A significant through
conjugation of the lone pair on the N1-atom towards the C3-aryl ring is observed when the
electron-withdrawing nitro group is located on the para-position of this aryl ring. The
experimental spectroscopic results for the substitution effects are also supported by
(TD)DFT/6-311++G(d,p) computed UV-Vis spectra. Experimental and theoretical NMR
chemical shifts and spin-spin coupling constants obtained for these 2-pyrazolines validated
by Karplus diagram approves the structures predicted for these compounds.
Keywords. UV-Vis, IR and NMR Spectroscopies; Electronic and steric effects; 2-
Pyrazolines; TD-DFT.
1. Introduction
The study and synthesis of nitrogen containing heterocyclic compounds are significant
due to the fact that these compounds have various pharmaceutical and medical properties. 2-

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Pyrazolines or 4,5-dihydropyrazoles and their oxidized form, pyrazoles (Scheme 1) are one of
the important class of heterocyclic compounds containing two adjacent nitrogen atoms, which
have different biological activities [1-8].
Scheme 1
Various works are devoted to elucidate the electronic effects of the heterocyclic ring
substitutions in 2-pyrazolines on some characteristic features of these compounds. The
electronic effects of ring substitutions in some 1-acetylpyrazolines and 2-naphthylpyrazolines
on the chemical shifts of characteristic heterocyclic ring hydrogens were investigated by
correlation of their spectral properties with the Hammett substituent constant and the Swain-
Lupton parameters [9,10]. In other studies, electronic effects of ring substitutions on the
photophysical properties, X-ray analysis and DFT B3LYP computational results were also
reported [11-13].
Our research interest concerns investigation of the steric and electronic factors of
substituents affecting the rate of thermal and photochemical oxidation, and cyclic
voltammetric measurement of nitrogen-containing heterocyclic compounds such as 1,4-
dihydropyridines
[14],
2-oxo-1,2,3,4-tetrahydropyrimidines
[15-18],
and
2,3-
dihydroquinazolinones [19,20] and 2-oxo-1,2,3,4-tetrahydropyridines [21,22].
In continuation to our previous studies, we decided to synthesis various 3- or 5-aryl
substituted 1-phenyl-2-pyrazolines containing electron-donor and electron-acceptor

3
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substituents on 3- or 5-aryl positions, in order to elucidate their steric and electronic
1
(inductive and resonance) effects on the UV-Vis, H NMR and IR spectra and also on the
DFT computational results.
2. Experimental and Computational Methods
2.1. Material and Synthetic Methods. All chemical used were purchased from Alfa Aesar,
Merck and Sigma-Aldrich companies. Melting points have been determined in open glass
capillaries on a Stuart Scientific SMP2 apparatus and are not corrected. Infrared spectra have
1
13
been recorded from KBr-discs on a Jasco FT/IR-6300 spectrometer. The H NMR and C
NMR spectra (DMSO-d6 or CDCl3) have been recorded on Bruker Avance III 400
spectrometers at 400 and 100 MHz at room temperature. The 1H NMR spectra are reported as
follows: chemical shifts, [multiplicity, number of protons, coupling constants J (Hz), and
assignment]. UV spectra were taken with Cary (500 scan) spectrometer.
A mixture of substituted chalcones (1 mmol) and phenylhydrazine hydrochloride (2
mmol) in EtOH (7 mL) was heated at 100 ºC for appropriate time. After completion of the
reaction indicated by TLC (n-hexane/ethyl acetate, 10:1), the reaction mixture was cooled to
room temperature. The solid products were filtered and washed with cold ethanol. The pure
products were obtained by recrystallization from ethanol. Physical and spectroscopic data are
given in Appendix and the complete spectra are provided in Supporting Information.
2.2. Computational Method. Geometries of 2-pyrazolines (1a-s) are optimized using the
density functional theory (DFT) B3LYP method with 6-311++G(d,p) basis set. The 1H NMR
chemical shifts of these optimized structures referenced to TMS were computed using the
gauge-invariant atomic orbitals (GIAO) method at the same level of theory in the conductor-
like polarizable continuum model (CPCM) solvent of DMSO. The nuclear-independent
chemical shift (NICS) [23,24] is also calculated for a selected set of derivatives using
independent individual gauges for atoms in molecules method (IGAIM). Time-dependent

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density functional theory (TD-DFT) B3LYP/6-311++G(d,p) method considering 10 excited
states is used in the presence of chloroform CPCM solvent. Furthermore, vibrational spectra
are calculated using harmonic oscillator analysis with a scale factor of 0.9614 [25]. All
computations are carried out using G09 program [26].
3. Results and Discussion
In order to elucidate the steric and electronic effects of the aryl substitutions on the C3-
or C5-positions of the heterocyclic ring on the spectroscopic behavior of the series of
compounds considered in the present work, the synthesis of 2-pyrazolines was carried out by
condensation of suitable chalcone precursors with phenylhydrazine hydrochloride in ethanol
under reflux condition (Scheme 2). The specific data are summarized in Table 1.
Scheme 2
Y
O
N
EtOH, 70 C
X
XC6H4CH
CHCC6H4Y
PhNHNH2.HCl
+
N
Table 1. Synthesized aryl substituted 2-pyrazoline compounds
Compound
Y
X
Time (h)
Yield (%)
M.P. (˚C)
H
4-Cl
3-Cl
2-Cl
H
H
H
6
8
3
5
7
3
71
82
70
45
85
87
134-136
148-150
129-131
122-125
131-133
106-108
1a
1b
1c
1d
1e
1f
H
H
4-Cl
3-Cl
H

5
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H
4-MeO
3-MeO
2-MeO
H
2-Cl
H
2.75
2
60
70
45
90
50
90
64
76
60
40
40
62
57
134-136
141-143
126-128
160-162
123-125
92-95
1g
1h
1i
H
4
H
6
1j
4-MeO
3-MeO
2-MeO
H
7
1k
1l
H
6.5
7.5
2
H
130-132
180-183
134-136
146-148
113-116
123-125
136-138
1m
1n
1o
1p
1q
1r
1s
4-NO2
3-NO2
2-NO2
H
H
7
H
6
4-NO2
3-NO2
2-NO2
5.8
7
H
H
4
1
The synthesized compounds were identified by obtaining and analyzing their H NMR,
UV-Vis and IR spectra. The substituted aryl ring on the C5-position of the heterocyclic ring
behaves as either a σ-donor or a σ-acceptor group due to its attachment to the sp3 hybridized
carbon atom. While, the substituted aryl ring on the C3-position of the heterocyclic ring can
possibly act as either a π-donor or a π-acceptor substituent. The C3-aryl ring is attached to the
sp2 hybridized carbon atom of the C=N double bond of the heterocyclic ring. Therefore, its
orientation relative to this double bond and also the possible co-planarity of the additional
substituent on the C3-aryl ring with this ring are important factors determining the extent of
its π-electron donor/acceptor ability.
The σ-donor/acceptor ability of substituted aryl ring on the C5-position depends on the
electronic nature and position of the additional substituent on this ring. For example, the
methoxy group (CH3O) on each position of the C5-aryl ring (as in 1k, 1l and 1m) acts as a σ-
acceptor group because of the inductive effect of its oxygen atom, whereas possible co-planar
orientation of this group especially on the para- and ortho-positions with the C5-aryl ring (1k

6
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and 1m) results in the delocalization of its oxygen lone pair towards the C-aryl ring (C18)
attached to the C5-atom of the heterocyclic ring. Consequently, as a balance of both negative
inductive and positive resonance effects of the methoxy group, this group behaves as a σ-
donor and thus an increase in the electron density of the heterocyclic ring via the σ-bond (C5‒
C18) is expected. In contrast to the behaviour of the methoxy group, the nitro group (NO2) on
the C5-aryl ring behaves as a σ-acceptor substituent on each position of the aryl ring due to its
electron-withdrawing character. In the case of co-planar orientation of this group with the
aryl ring, especially on the para- and ortho-positions (1q and 1s), delocalization of the π-
electrons towards the NO2 group via resonance causes a decrease of the electron density on
the C18-atom attached to the C5-atom, making its electron-withdrawing character more
pronounced. As a results of both negative inductive and negative resonance effects of the
NO2 group, a decrease of the electron density of the heterocyclic ring via the C5‒ C18 σ-bond
is expected.
The strength of the π-donor or π-acceptor character of the substituted aryl ring attached
to the C3-position of the heterocyclic ring depends on the extent of co-planarity orientation of
the additional substituent on the C3-aryl ring, especially on the para- and ortho-positions, and
also on the orientations of the C3-aryl ring towards the C3=N2 double bond. Keeping these
arguments in mind and considering also the orientation of the C5-aryl ring towards the
heterocyclic ring atoms, especially the C4-methylene hydrogens, the results of the
experimental spectroscopic data with the help of the results of DFT computational studies
will explain comparative spectroscopic characteristics of this series of compounds.
Another point to be considered in the present study is the effect of the nature of the
medium on some characteristic parameters in 2-pyrazolines. The attachment of the N1 atom
with phenyl ring and the conjugated imine double bond in the parent compound 1a, as
representative, allows delocalization of the N1 lone pair either to the conjugated imine group

7
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forming the resonance structure RS-I or to the N1-phenyl ring forming the resonance
structure RS-II as shown in Scheme 3. Due to the polar nature of DMSO solvent, it is
expected that upon delocalization of the N1-lone pair, the involvement of the zwitterionic
resonance structures RS-I and RS-II are more possible than unionized molecular structure.
The preference involvement of one of these resonance structures or unionized molecule
certainly depends on the nature of the additional substituent on the aryl ring, which has
already been observed in some of 2-pyrazoline derivatives [11,12].
Scheme 3
14
15
13
12
16
17
3
4
Ph
5
N
..
N
2
H
1
6
11
10
7
14
14
15
15
17
8
13
12
13
12
16
16
9
17
3
4
3
4
1a
Ph
H
Ph
5
5
N
N
2
2
H
N
N
1
1
6
6
11
10
11
10
7
7
8
8
9
9
RS-I
RS-II
In order to elucidate the effect of solvent on the data obtained by computational and
experimental studies, the optimized structures of 2-pyrazolines were obtained in the gas
phase and also in DMSO solvent. Comparative analysis of the computational data of the
parent compound 1a, as an example, in both phases (Table 2, and the data of the remaining 2-

8
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pyrazolines are provided in Table S1 of the Supporting Information) indicates that 1a in
DMSO medium seems to be more polar than in the gas phase, which is a result of more co-
planar orientation of the N1-phenyl ring towards the heterocyclic ring which allows better
delocalization of the N1-lone pair to this ring. Comparison of the bond lengths and dihedral
angles given in Table 2 supports the preferred involvement of the resonance structure RS-II
(Scheme 3). This contribution of the zwitterionic resonance structures is also supported by
higher stabilization of the compound 1a in DMSO (by ~25.54 kJ/mole) and the increased
dipole moment (from 2.6 D to 4.0 D) in DMSO compared to that in the gas phase.
Table 2. The optimized values of selected bond lengths and angels
obtained for the representative 2-pyrazoline 1a in the gas phase and
in the CPCM model of DMSO using B3LYP/6-311G++(d,p) method
Gas Phase
1.3655
1.3979
1.4808
1.2895
1.4631
DMSO
1.3672
1.3918
1.4827
1.2909
1.4643
N1−N2
N1−C6
N1−C5
N2−C3
C3−C12
C5−H
α
1.0956
-178.4
-167.8
-94.6
0.7
1.0933
-176.7
-172.9
-98.0
3.8
β
γ
ω
α = N2-C3-C12-C13, β = C5-N1-C6-C11
γ = C4-C5-C18-C23, ω = N1-C5-C4-C3
3.1. NMR Studies
The condensation of the chalcon precursors and phenylhydrazine hydrochloride results in
the formation of the enantiomeric pair for each 4,5-dihydropyrazole (1a-s) with the C5-atom
as the sole stereocenter. Analysis of the NMR spectra shows that, owing to the presence of
this stereocenter, the hydrogens on the neighbouring C4-atom are diastereotopic and appear as
two doublet of doublets upon coupling with each other and further coupling with 5-H.
Therefore, an AMX system, as expected, is observed for the geminal (4-CH2) and vicinal (5-

9
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1
CH) in the H NMR spectra of 1a-s. The benzylic proton Hx has the highest chemical shift
among the three protons of the AMX system. Also, between the two HA and HM
diastereotopic geminal protons, HA is more shielded because of the cis-orientation with
respect to the adjacent C5-aryl ring which induces a ring current shielding effect on this
proton. Characteristic 1H chemical shifts and the corresponding coupling constants measured
for 2,3-dihydropyrazoles (1a-s) are given in Table 3.
Table 3. Characteristic heterocyclic ring 1H chemical shifts (δ, ppm) and coupling constants (J,
Hz) of 2,3-dihydropyrazoles (1a-s) in DMSO-d6 derived from their NMR spectra
Y
H
X
H
δA
JAM
17.6
17.2
17.6
17.4
17.5
17.6
17.4
17.4
17.6
18.0
17.6
17.4
17.4
17.6
17.6
17.4
17.6
17.4
17.8
JAX
6.4
6.4
6.4
6.2
6.2
6.4
6.3
6.6
6.4
6.4
6.4
6.4
6.0
6.2
6.3
6.4
6.3
6.2
5.8
δM
JAM JMX
δX
JMX
12.4
12.4
12.4
12.2
12.2
12.4
12.2
12.2
12.4
12.0
12.0
12.2
12.1
12.6
12.5
12.4
12.4
12.2
12.4
JAX
6.4
6.4
6.4
6.2
6.2
6.4
6.2
6.6
6.4
6.4
5.8
6.4
6.0
6.2
6.3
6.4
6.3
6.2
5.6
δ
MeO
1
a
b
c
d
e
3.11
3.11
3.21
3.22
3.12
3.16
3.09
3.08
3.11
3.17
3.08
3.11
3.01
3.19
3.28
3.17
3.17
3.22
3.31
3.93
3.91
3.99
4.05
3.92
3.92
4.02
3.80
3.91
3.98
3.88
3.91
3.92
3.98
4.05
4.01
3.98
3.98
4.08
17.6
17.6
17.6
17.4
17.5
17.6
17.6
17.4
17.6
18.0
17.6
17.4
17.4
17.6
17.6
17.4
17.6
17.4
17.8
12.4
12.4
12.4
12.2
12.2
12.0
12.4
12.2
12.4
12.0
12.0
12.2
12.1
12.6
12.5
12.4
12.4
12.2
12.4
5.48
5.51
5.60
5.50
5.52
5.53
5.69
5.42
5.48
5.39
5.43
5.44
5.62
5.65
5.66
5.59
5.68
5.73
5.91
4-Cl
3-Cl
2-Cl
H
H
H
H
4-Cl
3-Cl
2-Cl
H
H
f
H
g
h
i
j
k
l
m
n
o
p
q
r
3.79
3.81
3.77
3.71
3.71
3.92
4-MeO
3-MeO
2-MeO
H
H
H
4-MeO
3-MeO
2-MeO
H
H
H
4-NO2
3-NO2
2-NO2
H
H
H
4-NO2
3-NO2
2-NO2
H
H
s
The assignment of HA and HM signals was achieved by comparison of the corresponding
experimental vicinal long-range coupling constant with HX, namely, JAX and JMX, and
comparison of the correlation of their DFT calculated dihedral angles (ϕ1 = HA‒C4‒C5‒HX
and ϕ2 = HM‒C4‒C5‒HX in Fig 1) with the expected J values, considering the Karplus

10
ACCEPTED MANUSCRIPT
equation [27]. According to this equation, the coupling constant is varied by changing the ϕ
dihedral angle and is expected to increase by going from ϕ = 90º towards either ϕ = 0º or
180º. Therefore, a larger coupling constant (JMX) is expected for spin-spin coupling between
the HM and HX protons as compared to that between the HA and HX protons (JAX), namely, HA
is cis-orientated towards the C5-aryl substituent (i.e. HA is trans-orientated towards the HX).
The spectral data presented in Table 3 indicate that, as expected, the coupling constants are
not varied drastically by changing the electronic nature and positions of the additional
substituents either on the C3- or C5-aryl ring, whereas the electronic and steric effects of these
substituents influence the characteristic chemical shifts of protons of this AMX system.
Fig 1. The dihedral angles ϕ1 = HA-C4-C5-HX and ϕ2 = HM-C4-C5-HX
defining the J-coupling in the AMX system corresponding to Karplus
diagram in the structures of 2-pyrazolines (1a-s, Table 1).
In order to elucidate the steric and electronic effects of the additional substituent
1
especially on the C5-position on the experimental H chemical shifts and corresponding
coupling constants of the heterocyclic hydrogen atoms (AMX system), computational studies
were carried out using density functional theory (DFT) B3LYP method with the 6-
311++G(d,p) basis set. Results of these computations are reported in Table 4. Comparison of
1
the H NMR data of the methoxy substituted derivatives on the 4-, 3- and 2-positions of the
C3-aryl ring (1h, 1i and 1j) and on the C5-aryl ring (1k, 1l and 1m) indicates that π-donor and
σ-donor characters of the methoxy group on the chemical shift of C5‒Hx proton, compared to
those in the parent compound 1a, is not drastic and only in the case of 2-CH3O group on the
C5-aryl position (1m), downfield shift of the Hx proton (C5‒Hx) from 5.48 to 5.62 ppm is

11
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observed. DFT optimized structure of 1m shown in Fig 2 indicates that due to the attachment
of C5 atom to the electronegative N1 atom, the hydrogen atom in C5‒Hx bond is relatively
more polarized than a normal C-H bond, and therefore, the oxygen atom of the 2-CH3O
group is orientated towards the C5‒Hx hydrogen atom because of significant electrostatic
interaction resulting in a 2.4399 Å distance. This interaction partly explains the downfield
shift of this Hx proton in 1m.
Fig 2. DFT optimized structures of 1m (left) and 1s (right) in DMSO (CPCM model
solvent) showing the significant intramolecular electrostatic interactions between
the hydrogen of the C5‒Hx bond and the oxygen atoms of the methoxy and nitro
groups, respectively.
Comparison of the 1H NMR data of the nitro-substituted derivatives on the 4-, 3- and 2-
positions of the C3-aryl ring (1n, 1o and 1p) and on the C5-aryl ring (1q, 1r and 1s) indicates
clearly the effective π- and σ-electron-withdrawing characters of nitro-substituted aryl ring
changing the chemical shifts of all three hydrogen atoms of the heterocyclic ring, compared
to those in the parent compound 1a. The more effective downfield shift observed for the Hx
proton (C5‒Hx) from 5.48 to 5.91 ppm in compound 1s, having the NO2 group on the ortho-
position of C5-aryl ring, is attributed to the intramolecular electrostatic interaction of one of
the oxygen atoms of this nitro group with the hydrogen of the polarized C5‒HX bond with a

12
ACCEPTED MANUSCRIPT
distance of 2.3213 Å. In this compound, plane of the nitro group is deviated from ring co-
planarity by 28.4º (as compared to 0.5º and 0.4º in 1q and 1r, respectively) to orient towards
the Hx, HA and HM to have more effective interactions, as shown in Fig 2. In addition, the
higher vibrational frequencies calculated for the C5-Hx stretching for 1m and 1s as compared
to that in the reference compound 1a (see the IR section below) support the suggestion of the
intramolecular electrostatic interaction of the methoxy and nitro substitutions at the ortho-
position respectively in 1m and 1s with the hydrogen of C5-HX bond.
The electron-withdrawing inductive effect of the chlorine atom causes also downfield
shift of the protons of the AMX system. The steric and electronic effects of the additional
substituents on the C3- and C5-aryl groups on the J-coupling constants are explained
considering results of the DFT computations reported in Table 4, to be compared with the
corresponding experimental values reported in Table 3. These chemical shifts and J-coupling
constants are calculated using the GIAO methods, respectively.
Table 4. The dihedral angles and the calculated chemical shifts and J-coupling
constants for the AMX system obtained for 2-pyrazolines 1a-1s in their B3LYP/6-
311++G(d,p) structures optimized in the CPCM model solvent of DMSO
Comp.
1a
δA
δM
δX
JAM
16.7
16.7
16.6
17.0
16.7
16.7
16.4
16.7
16.6
17.6
16.6
16.7
16.3
ϕ1
JAX
5.4
5.4
5.3
9.8
5.7
6.1
4.8
6.3
5.3
3.9
4.7
5.3
4.3
ϕ2
0.2
0.2
0.8
14.8
0.8
2.6
3.5
2.8
0.4
6.5
2.7
4.2
6.1
JMX
13.5
13.5
13.6
12.6
13.5
13.5
13.5
13.3
13.5
13.5
13.3
13.5
13.2
3.11
3.07
3.08
4.00
3.11
3.14
3.05
3.07
3.13
3.09
3.08
3.11
2.98
4.13
4.07
4.05
3.87
4.11
4.13
4.27
4.09
4.13
4.60
4.06
4.10
4.17
5.41
5.42
5.52
5.42
5.40
5.34
5.78
5.30
5.45
5.46
5.41
5.38
5.87
120.3
120.3
119.7
135.1
121.3
123.1
117.2
123.4
120.1
114.2
117.8
124.7
114.7
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m

13
ACCEPTED MANUSCRIPT
3.13
3.13
3.07
3.14
3.13
3.28
4.05
4.10
3.50
4.18
4.19
4.44
5.66
5.59
5.63
5.52
5.52
5.78
16.5
16.6
16.7
16.7
16.8
17.0
117.3
118.5
115.7
123.8
120.9
116.9
4.9
5.1
4.5
6.5
5.6
4.9
3.2
2.1
5.1
3.2
0.3
3.6
13.6
13.6
13.4
13.7
13.6
13.3
1n
1o
1p
1q
1r
1s
As can be seen in Table 4, the JMX values are generally larger than the corresponding JAX
values because of larger distance of the ϕ2 from 90º reference orientation as compared to the
ϕ1 dihedral angle, which is consistent with the Karplus diagram. These results shows that the
vicinal J-coupling constants of the AMX spin system reflect the HA/M-C4-C5-Hx dihedral
angles which is determined by nature and position of the substituent on the C3- and C5-aryl
rings. Furthermore, the steric hindrance of the substituent on the 2-position of these aryl rings
has the most significant effect on the JAX and JMX values. Finally, comparative analysis shows
that variation trends of the experimental (Table 3) and calculated (Table 4) chemical shifts
with the substituents on the C3- and C5-aryl rings are similar.
After examining the NMR spectra, it was found out that in some derivatives, the
substituent effects on the proton chemical shifts are not as expected. In addition to the
important factors including inductive, resonance and through space (field) effects used
usually to describe the substituent effects, the aromatic current ring, changed by the nature
and position of the additional substituent, is also another significant factor affecting the NMR
characteristics. Specifically, for the HA, HM and HX protons of the AMX system described
above, which are close to the C5-aryl ring, this ring current can contribute to the NMR
chemical shifts of these protons through space depending on the orientation of this aryl ring
relative to the heterocyclic ring. To investigate this contribution, the (NICS) induced by this
ring current is calculated for a point (Bq) located 0.5 Å above the center of the C5-aryl ring in

14
ACCEPTED MANUSCRIPT
the B3LYP/6-311++G(d,p) optimized structures (Fig 3) of a selected set of derivatives using
(IGAIM) method.
Fig 3. Position of the Bq point for which the NICS is
calculated for this family of compounds (left) and in the
optimized structure of 1a as representative (right).
The calculated NICS values are presented in Fig 4 where they have been compared with
the corresponding calculated and experimental chemical shifts of the AMX system protons. A
complete correlation between variations of the NICS values at the Bq site and the chemical
shifts of a specific proton denotes important contribution of the ring current to these chemical
shifts. It is basically not possible to isolate the effects of each inductive, resonance, field and
ring current contributions, since chemical shift is determined by collective effects of these
factors which depend differently on the nature and position of the additional substituents. For
the specific Bq point selected in this NICS analysis, an upfield shift in the NICS value
correspond to an opposite (downfield) shift in the chemical shift of the protons located in-
plane with the aryl ring. Therefore, the negative sign of the NICS values are omitted in Fig 4.
As can be seen from this Fig, the calculated chemical shifts of the Hx proton has the best
correlation with the NICS at the Bq point due to the closer position to the C5-aryl ring and
stronger feeling of its ring current. While, the HA and HM protons show weaker correlation
because of their farther positions from this ring. Comparison of the AMX system calculated
chemical shifts in the methoxy-substituted C5-aryl ring (1k,1l,1m) shows that chemical shifts

15
ACCEPTED MANUSCRIPT
of the AMX protons of compound 1m have the least match with the NICS value at the Bq
point, which can be attributed to their farther positions from co-planarity with the C5-aryl ring
(e.g. compare the HX-C5-C18-C23 dihedral angels 26.8°, 27.5° and 39.4° for the 1k, 1l and 1m,
respectively). Interaction between the methoxy O atom and the HX proton, described above in
Fig 2, partially cancels this effect of relative orientation in the 1m compound. Among 2-
pyrazolines 1q, 1r and 1s, having nitro-substitution on different positions of the C5-aryl ring,
the best agreement between the NICS values and the calculated chemical shifts belongs to the
1s compound in the order of HA > HM > HX. These trends, which are opposite to what
observed for the methoxy-substituted derivatives 1k, 1l and 1m, can be explained in terms of
the smaller difference between the relative orientations of the AMX system with the C5-aryl
ring (e.g. note the calculated dihedral angles HX-C5-C18-C23 28.9°, 28.0° and 32.7° for the 1q,
1r and 1s, respectively) and stronger donor-acceptor interactions between the oxygen atom of
the nitro group and the AMX protons in the strength order of HA < HM < HX based on the O-
H distances labeled in Fig 2. These evidences denote diminished effect of the current ring for
this series of compounds compared to the local interactions.
A comparative analysis of the experimental and computational chemical shifts presented
in Fig 4, shows evidently that trends observed for the variations of these two sets of chemical
shifts for the methoxy- and nitro-substituted C5-aryl ring (as in 1k, 1l, 1m and 1q, 1r and 1s
derivatives) are similar. The compatibility of the calculated 1H NMR chemical shifts obtained
in the presence of the CPCM model solvent of DMSO is much better than that of obtained in
the gas phase.

16
ACCEPTED MANUSCRIPT
Derivatives
Derivatives
Fig 4. The IGAIM NICS values calculated at the point Bq (Fig. 3) for selected C5-aryl
substituted 2-pyrazolines, methoxy derivatives 1k, 1l, and 1m (left column) and nitro
derivatives 1q, 1r, and 1s (right column), compared to the corresponding calculated and
experimental chemical shifts of the AMX protons (Fig. 1 and 2). All values are referenced
with respect to those of the unsubstituted 2-pyrazoline (1a). The data obtained
computationally in the gas phase are also presented for comparison.
3.2. UV-Vis Study
Electron-donor acceptor abilities of the substituted aryl rings on the 3- and 5-positions of
the heterocyclic ring were investigated by UV-Vis spectroscopy. The UV-Vis spectra of 2-

17
ACCEPTED MANUSCRIPT
pyrazolines 1a-s were obtained in CHCl3 and the characteristic UV-Vis absorptions are
presented in Table 5.
Table 5.
Important electronic UV-Vis absorptions obtained
experimentally for the aryl substituted 1-phenyl-2-pyrazolines (1a-s,
scheme 1) in CHCl3
Y
H
X
H
λmax (log ε) in nm
1
a
b
c
355 (4.32), 313 (sh, 3.96), 241 (4.30)
367 (4.36), 315 (sh, 3.92), 243 (4.31)
367 (4.34), 312 (sh, 3.84), 246 (4.22)
357 (4.19), 314 (sh, 3.89), 246 (4.13)
355 (4.26), 242 (4.23)
4-Cl
3-Cl
2-Cl
H
H
H
H
d
e
4-Cl
3-Cl
2-Cl
H
H
356 (4.28), 316 (sh, 3.97), 240 (4.21)
355 (4.25), 316 (sh, 3.92), 240 (4.19)
354 (4.17), 321 (sh, 3.97), 250 (4.16)
360 (4.27), 241 (4.12)
f
H
g
h
i
4-CH3O
3-CH3O
2-CH3O
H
H
H
357 (4.34), 251 (4.28)
j
4-CH3O
3-CH3O
2-CH3O
H
357 (4.29), 315 (sh, 3.95), 239 (4.27)
356 (4.22), 241 (4.17)
k
l
H
H
360 (4.27), 315 (sh, 3.92), 243 (4.24)
446 (4.35), 267 (4.21)
m
n
o
p
q
r
4-NO2
3-NO2
2-NO2
H
H
354 (4.17), 321 (sh, 3.97), 250 (4.16)
350 (4.13), 296 (sh, 3.96), 246 (4.27)
350 (4.31), 249 (4.32)
H
4-NO2
3-NO2
2-NO2
H
351 (4.20), 247 (4.26)
H
353 (4.36), 313 (sh, 4.09), 243 (4.36)
s

18
ACCEPTED MANUSCRIPT
The nature of the substituents considered in the present study, compared to the phenyl-
substituted parent compound 1a, is classified as strong electron-donating or activating (CH3O
group), strong electron-withdrawing or deactivating (NO2 group) and weak deactivating but
electron-donating (chlorine atom) substituents. As is mentioned earlier, the substituted aryl
ring can be considered as a σ-donor or as a σ-acceptor substituent due to its attachment to the
sp3 hybridized carbon atom, namely, C5-position of the heterocyclic ring, while these
substituents themselves can possibly behave as π-donor or π-acceptor substituent due to the
attachment to the sp2 hybridized carbon atom of the C3-position. Comparison of the UV-Vis
spectral data (Table 5) of 2-pyrazolines containing chlorine atom on the 4-, 3- and 2-
positions either of the C3-aryl ring (1b, 1c and 1d) or of the C5-aryl ring (1e, 1f and 1g)
indicates that the maximum absorption wavelengths for 1d, 1e, 1f and 1g do not differ from
that of 1a. The observed bathochromic shift in the absorption peaks of compounds 1b and 1c
(of ca. 10 nm) compared to that of 1a and other chlorine containing compounds can be
possibly due to the electron donating of the para- and meta-substituted C3-aryl ring towards
the electron-withdrawing imine bond (C=N) of the heterocyclic ring, which changes the
spacings between the HOMOs and LUMOs energy levels contributing to the UV transitions.
The observed lower wavelength of the absorption peak of 1d (at 357 nm), compared to those
of the two corresponding compounds 1b and 1c (at 367 nm), can be attributed to the non-
coplanar orientation of the 2-chlorophenyl and heterocyclic rings due to steric hindrance of
the chlorine atom with CH2 moiety, which is approved by the results of B3LYP/6-
311++G(d,p) computations carried out in the chloroform CPCM solvent. Comparison of the
optimized value of the dihedral angle α = N2-C3-C12-C13 in 1d (154.1°) with those in 1b
(177.7°) and 1c (178.6°) supports this suggestion. This is while, almost identical UV-Vis
spectrum obtained for the 1e, 1f and 1g compounds (Fig 5) indicates that the chlorophenyl
substitution at the C5-position has no significant effect on the UV-Vis transitions since these

19
ACCEPTED MANUSCRIPT
substitutions contribute to the electronic structure of compound only via the σ-bond. These
observations and justifications are approved by the calculated UV-Vis transition energies and
spectra which are reported in Table S2 of the Supporting Information. For these calculations
time-dependent density functional theory (TD-DFT) B3LYP/6-311++g(d,p) method
considering 10 excited states is used in the presence of chloroform CPCM solvent in
accordance with the experimental conditions. Computations show also that the chloro
substitution on the C3-aryl ring in 1b and 1c lowers both HOMO and LUMO energies as
compared to those of the parent compound 1a, such that their HOMO-LUMO energy
spacings (see Table S2 of the Supporting Information) are reduced and thus results in an
increase in their maximum absorption wavelengths.
Interestingly, comparison of the UV-Vis spectra (Fig 5) of the para-substituted
chlorophenyl group on the C3- and C5-positions, respectively in 1b and 1e, with that of 1a,
indicates that the σ-donor ability of para-chlorophenyl substituent in 1e does not affect its
maximum absorption as opposed to the significant red shift observed for 1b due to its π-
donor ability. The weak σ-donor ability of the chlorophenyl substituent on the C5-position is
also supported by obtaining almost the same UV-Vis absorption spectra for 1e, 1f and 1g,
(Fig 5) having the chlorine atom respectively on the para-, meta- and ortho-positions on the
C5-aryl ring (Table 5).

20
ACCEPTED MANUSCRIPT
Fig 5. Comparison of the UV-Vis spectra of 1b and 1e containing 4-
chlorophenyl substituted C3- and C5-aryl rings with that of 1a showing the
π-donor ability of the group in 1b versus its σ-donor ability in 1e (a). Almost
identical UV-Vis spectra obtained for the 1e, 1f and 1g, are shown in (b).
Maximum UV-Vis absorptions of the methoxyphenyl-substituted 2-pyrazolins on the C3-
(1h, 1i and 1j) and C5-positions (1k, 1l and 1m) are given in Table 5. Comparison of their
UV-Vis spectra with that of the parent compound 1a indicates that the difference between the
π- and σ-donor abilities of the methoxyphenyl substitutions is not drastic. This supports the
suggestion that the heterocyclic ring is not an electron-accepting group against the
methoxyphenyl group.
Interesting trends have been observed by comparison of the maximum UV-Vis
absorptions of the 1n, 1o and 1p (with para-, meta- and ortho-nitrophenyl substituents at C3-

21
ACCEPTED MANUSCRIPT
position), and 1q, 1r and 1s (with para-, meta- and ortho-nitrophenyl substituents at C5-
position) shown in Fig 6.
Fig 6. Comparison of the experimental UV-Vis absorption spectra
of 1n, 1o and 1p containing respectively para-, meta- and ortho-
nitrophenyl group on the C3-position of the heterocyclic ring, (top),
and of C3- and C5-para-nitrophenyl substituted 2-pyrazolines with
that of 1a (bottom).
The observed bathochromic shift of the UV-Vis absorption peak of 1n is explained by
through conjugation of the lone pair on the N1-atom of the heterocyclic ring towards the
electron-withdrawing NO2 group at the para-position of the C3-aryl ring. It is basically
expected that the co-planar orientation of the electron-pulling NO2 group on the ortho- and
para-positions, either on C3- or C5-aryl rings, results in the induction of the positive charge
on the C-atom of the aromatic ring attached to the C3- or C5-atoms of the heterocyclic ring.

22
ACCEPTED MANUSCRIPT
Whereas the electron-withdrawing effect of this group on the C5-position via the σ bond (C18-
C5 bond) decreases the electron-donating ability of the heterocyclic ring, co-planar
orientation of the C3-aryl ring with the C3=N2 double bond allows effective delocalization of
the lone pair of the N1-atom towards the positive charge in the proposed resonance structure
illustrated in Fig 7, which we will assign as through conjugation from the N1-lone pair
towards the electron-pulling NO2 group either on the ortho- or para-position. This is
indicated by appearance of the intensive color and the effective visible light absorption of
compound 1n as shown in Fig 7. The effective and strong π-electron pulling effect of the
para-nitrophenyl group on the C3-position (compound 1n) versus its weak σ-electron pulling
effect on the C5-position (compound 1q) can be deduced from the UV-Vis absorption peaks
shown in Fig 6.
O
N
O
O
N
Ph
O
3
3
Ph
H
N
N
O
N
5
H
5
N
N
1
1
Ph
O
Ph
O
N
1n
1q
Ph
O
3
3
Ph
H
N
N
5
H
5
N
N
1
1
O
N
Ph
Ph
O
3
Ph
N
5
H
N
1
Ph

23
ACCEPTED MANUSCRIPT
1a
1n
1q
Fig 7. The observed through conjugation from N1-lone pair towards the para-nitrophenyl
group on the C3-position in 1n causes effective visible light absorption compared to that in
1q and the parent compound 1a.
Surprisingly, a comparison of the UV-Vis absorption of the para- and ortho-nitrophenyl
substituted compounds 1n and 1p does not show effectively the through conjugation in
compound 1p. As can be seen in Table 5 and Fig 6, position of the UV absorption peak (at
350 nm) of compound 1p does not significantly differ from that of parent compound 1a (at
355 nm). This can be attributed to the special non-co-planar inter-ring (α dihedral angle) and
NO2‒ring (θ dihedral angle) conformations adopted in this compound (computed respectively
to be α = 149.6° and θ = ‒34.1° dihedral angles, as defined in Fig 8) prevents through
conjugation from the heterocyclic ring nitrogen atom to the NO2 group, which does not allow
the NO2 group to act as an effective π-acceptor, while still acting as a σ-acceptor. Therefore,
the UV peak of 1p resembles that of 1o in which the nitro group in the meta-position acts also
as a σ-acceptor.

24
ACCEPTED MANUSCRIPT
α =149.6 °
θ = ‒34.1°
Fig 8. The optimized conformation of the 1p compound showing the
orientation of the C3-aryl ring with respect to the heterocyclic ring (defined by
the dihedral angle α = N2-C3-C12-C13) and the orientation of the NO2
substitution with respect to the C3-aryl ring plane (defined by the dihedral angle
θ = O25A-N24-C13-C12).
The tendency of the heterocyclic ring towards the C3-substituted aryl ring of different
natures, namely, the electron-donating para-methoxy group in 1h versus the electron-
withdrawing para-nitro group in 1n was elucidated by comparison of the experimental and
calculated UV spectra with those of the parent compound 1a (Fig 9). A detailed analysis of
the two sets of UV-Vis spectra (Tables 5 and S3-S5) shows a close correlation between the
experimental and computational UV-Vis absorption wavelengths (energies), although the
numerical values of the two sets are not exactly compatible. The differences between these
values can be attributed mainly to the well-known gas-to-liquid shift due to specific, mainly
solute-solvent, interactions in the form of electrostatic and hydrogen bonding [28], in addition
to the limitations and approximations of the theoretical method used in our calculations.
Based on the data reported in Tables S3-S5, the theoretical and experimental absorption
wavelengths are in relatively good agreement for the 1a and 1h, but not for the 1n compound.
Also, the differential wavelengths of the two peaks in the theoretical spectra, ∆λmax(theo) =
λmax1(theo) - λmax2(theo), and in the experimental spectra, ∆λmax(exp) = λmax1(exp) -
λmax2(exp), for the 1n compound is larger (40.6 nm) than those for the 1a (17.5 nm) and 1h

25
ACCEPTED MANUSCRIPT
(12.8 nm) compounds. This can be attributed to the more profound solvent effect for the 1n
compound due to its stronger electrostatic interactions with the solvent which is approved by
its larger calculated dipole moment (9.3064 Debye) as compared to the smaller dipole
moments of 1a and 1h (3.6129 and 2.7832 Debye, respectively). The preferred delocalization
of the N1 lone pair towards the C3-aryl ring allows the occurrence of the resonance structure
type RS-I (Scheme 3), which is more stabilized by the electron-withdrawing resonance effect
of the nitro group on the 4-position illustrated in Fig 7. These suggestions are supported by
larger calculated dipole moment for this compound mentioned above, and consequently,
higher solute/solvent interaction for 1n is expected. Computations with the explicit solvent
molecules can greatly improve theoretical results but is not intended in this work. However,
the TD-DFT computations have reproduced fairly well comparative intensities of the UV-Vis
peaks, and even the shoulders of the UV-Vis spectra demonstrated in Fig 9.

26
ACCEPTED MANUSCRIPT
Fig. 9. The computational (left) and experimental (right) UV-Vis absorption spectra of 1a, 1h
and 1n in CHCl3, showing the effects of the –OCH3 and –NO2 groups on the para-position of the
C3-aryl ring of the 2-pyrazolines studied in this work. The arrows, pointing the shoulders, show
further agreement of the calculated and experimental spectra. In the lowest row, all these UV-Vis
spactra are plotted together for better comparison.
3.3. IR Study
The infrared spectra of the 2-pyrazolines 1a-s have been obtained and the main stretching
bands are assigned and presented in Tables S6-S9 in the Supplementary Information.
Analysis of these experimental IR bands [29] reflect the resonance and inductive effects of
the substituents, which is more remarkable for some derivatives. For example, the C=N
stretching frequency in 1a, 1h and 1n compounds are respectively 1596 cm-1, 1600 cm-1 and
1593 cm-1 (Fig 10, left column), which denote the presence of through conjugation in 1n
compound due to the electron-withdrawing resonance effect of 4-nitro group versus electron-
donating nature of 4-methoxy group in 1h compared to that in 1a. This conjugation can also
be deduced by comparing the C3=N2 & N=O (nitro) and C5-N1 & C5-HX stretching
frequencies of the four 1a, 1n, 1o and 1p compounds, which are respectively the lowest and

27
ACCEPTED MANUSCRIPT
highest for 1n (Fig 11). The observed shifts of the corresponding C5-HX bands in the 1n
compound to higher frequencies, is explained by the effective through conjugation in the
proposed resonance structure described in Fig 7, results in a positive charge on the N1-atom
of the heterocyclic ring which leads to stronger C5-N1 and C5-HX bonds via induction effect.
In addition, the B3LYP/6-311++G(d,p) calculated higher vibrational frequencies of the C5-H
stretching for 1m (at 3076.43 cm-1) and 1s (at 3097.90 cm-1) as compared to that in the
reference compound 1a (at 3042.67 cm-1) (Fig 10, right column) support the suggestion of the
intramolecular electrostatic interaction of the ortho-substitution in 1m and 1s with the HX
hydrogen atom of the C5-HX bond, as discussed in the NMR section above.
Fig. 10 The experimental (top row) and computational (bottom row) IR spectra
obtained for 1a, 1h and 1n (left column) and 1a, 1m and 1s (right column), showing
the effects of the CH3O and NO2 groups on the para-position of the C3-aryl ring and
on the ortho-position of the C5-aryl ring of the 2-pyrazoline structure (Table 1).

28
ACCEPTED MANUSCRIPT
Since, the C=N stretching bands for the (1a, 1m and 1s) and C-H streching bands
for the (1a, 1h and 1n) sets of compounds are similar, the corresponding regions are
not shown.
Fig. 11 The experimental (top row) and computational (bottom row) IR spectra
obtained for 1a, 1n, 1o and 1p showing the effects of the NO2 group on the para-,
meta- and ortho-positions of the C3-aryl ring of the 2-pyrazoline structure (Table 1)
on the C3=N2 stretching bands and C5-HX streching bands for these compounds.
The broad bands appearing at the highest frequency of the experimental IR spectra (Fig
10) which are assigned to the stretching vibrations of the C-H bonds of the three aryl rings,
denote variations of the orientations and inter-molecular interactions experienced by these
aryl rings in the bulk of solid sample milled and dispersed in the KBr tablet. These variations
of the electronic environment are not included in the DFT computations, and thus such a
broad band is expected to be missing in the computed IR spectra, as can be seen in Fig 10. It