Spectroscopic (FT-IR, FT-Raman, UV, 1H and 13C NMR) profiling and theoretical calculations of (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]hydrazinecarboxamide: An anticonvulsant agent

Article abstract of DOI:10.1016/j.molstruc.2016.04.026

Vibrational characteristics of the anticonvulsant agent, (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]hydrazinecarboxamide ((2E)-IPHC) have been investigated. The computational data are obtained by adopting ab initio Hartree-Fock (HF) and DFT/B3LYP/6-31 + G(d,p) methods. The most stable conformer is identified by a potential energy scan. The optimized geometrical parameters indicated that the overall symmetry of the most stable conformer is C_S. Atoms in molecules (AIM) analysis is contained out and the chemical bondings between the atoms are as characterized. Mulliken atomic charges and simulated thermo-molecular (heat capacity and enthalpy) characteristics of the (2E)-IPHC molecule also have been analyzed. The magnitude of the molecular electrostatic potential (MEP) of oxygen, hydrogen, and nitrogen atoms as well as phenyl and imidazole rings in the title molecule were investigated along with their contribution to the biological activity. The energy gap between HOMO and LUMO orbitals has been found to be 5.1334 eV in the gaseous phase. Excitation energies, oscillator strength and wavelengths were computed by the time-dependent density function theory (TD-DFT) approach. Predicted wavenumbers have been assigned and they are consistent with the experimental values. The ¹H and ¹³C nuclear magnetic resonance (NMR) chemical shifts of the (2E)-IPHC molecule were computed by the gauge independent atomic orbital (GIAO) method and were compared with the experimental results.

Full text of DOI:10.1016/j.molstruc.2016.04.026

Accepted Manuscript
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Spectroscopic (FT-IR, FT-Raman, UV, H and C NMR) profiling
and theoretical calculations of (2E)-2-[3-(1H-imidazol-1-yl)-1-
phenylpropylidene]hydrazinecarboxamide: an anticonvulsant agent
Nadia G. Haress, Munusamy Govindarajan, Reem I. AL-Wabli, Maha S. Almutairi,
Monirah A. Al-Alshaikh, Abdulaziz A. Al-Saadi, Mohamed I. Attia
PII:
S0022-2860(16)30335-0
10.1016/j.molstruc.2016.04.026
MOLSTR 22440
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 25 January 2016
Revised Date: 7 April 2016
Accepted Date: 8 April 2016
Please cite this article as: N.G. Haress, M. Govindarajan, R.I. AL-Wabli, M.S. Almutairi, M.A. Al-
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Alshaikh, A.A. Al-Saadi, M.I. Attia, Spectroscopic (FT-IR, FT-Raman, UV, H and C NMR) profiling
and theoretical calculations of (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]hydrazinecarboxamide:
an anticonvulsant agent, Journal of Molecular Structure (2016), doi: 10.1016/j.molstruc.2016.04.026.
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Spectroscopic (FT-IR, FT-Raman, UV, 1H and 13C NMR) profiling and theoretical
calculations of (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]hydrazinecarboxamide:
an anticonvulsant agent
Nadia G. Haressa, Munusamy Govindarajanb,c*, Reem I. AL-Wablia, Maha S. Almutairia,
Monirah A. Al-Alshaikhd, Abdulaziz A. Al-Saadie and Mohamed I. Attia a,f*
aDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O.
Box 2457, Riyadh 11451, Saudi Arabia
bDepartment of Physics, BGCW, Puducherry, India
cDepartment of Physics, AGCW, Karaikal Puducherry, India
dDepartment of Chemistry, College of Sciences, King Saud University, Riyadh 11451, Saudi
Arabia
eDepartment of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 31261,
Saudi Arabia
fMedicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries
Research Division, National Research Centre (ID: 60014618), El Bohooth Street, Dokki, Giza
12622, Egypt
Abstract
Vibrational characteristics of the anticonvulsant agent, (2E)-2-[3-(1H-imidazol-1-yl)-1-
phenylpropylidene]hydrazinecarboxamide ((2E)-IPHC) have been investigated. The
computational data are obtained by adopting ab initio Hartree-Fock (HF) and DFT/B3LYP/6-
31+G(d,p) methods. The most stable conformer is identified by a potential energy scan. The
optimized geometrical parameters indicated that the overall symmetry of the most stable
conformer is CS. Atoms in molecules (AIM) analysis is contained out and the chemical bonding
between the atoms are as characterized. Mulliken atomic charges and simulated thermo-
molecular (heat capacity and enthalpy) characteristics of the (2E)-IPHC molecule also have been
analyzed. The magnitude of the molecular electrostatic potential (MEP) of oxygen, hydrogen,
and nitrogen atoms as well as phenyl and imidazole rings in the title molecule were investigated
along with their contribution to the biological activity. The energy gap between HOMO and
LUMO orbitals has been found to be 5.1334 eV in the gaseous phase. Excitation energies,
oscillator strength and wavelengths were computed by the time-dependent density function
theory (TD-DFT) approach. Predicted wavenumbers have been assigned and they are consistent
with the experimental values. The 1H and 13C nuclear magnetic resonance (NMR) chemical shifts
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of the (2E)-IPHC molecule were computed by the gauge independent atomic orbital (GIAO)
method and were compared with the experimental results.
Keywords: Imidazole; FT-IR; FT-Raman; HOMO-LUMO; DFT/B3LYP
1. Introduction
Epilepsy is an idiopathic ubiquitous syndrome that has been recognized as a serious brain
disorder afflicting more than 60 million people according to epidemiological studies [1].
Annually, about 0.25 million new individuals are added to this figure [2]. Epilepsy is
characterized by a sudden onset of spontaneous convulsive and non-convulsive seizures and
episodes of sensory, motor or autonomic phenomenon with or without a loss of consciousness
[3,4]. In spite of the enormous therapeutic arsenal of several generations of antiepileptic drugs
(AEDs), only 65–75% of epileptic patients achieve adequate control with the currently available
AEDs [5,6].
Conventional antiepileptic agents (carbamazepine and phenytoin) and recent antiepileptic
drugs (loreclezole, vigabatrin, remacemide, and gabapentin) are clinically useful for the
management of different types of epilepsy. Nevertheless, many AEDs have serious side effects
[7–9]. Accordingly, the continued search for safer and more effective AEDs is necessary.
(2E)-2-[3-(1H-Imidazol-1-yl)-1-phenylpropylidene]hydrazincarboxamide ((2E)-IPHC)
displayed anticonvulsant activity with 50% seizure protection at a dose of 972 ꢀmol/kg in a
subcutaneous pentylenetetrazole (scPTZ) screen and showed no neurotoxicity [10]. Although a
literature review indicated that some spectroscopic studies of certain imidazoles already have
been documented [11–13], the molecular structure of this molecule has not previously been
reported using computational methods. Accordingly, the present work deals with vibrational
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investigations as well as spectral (FT-IR, FT-Raman, UV, H and C NMR) characterization of
the (2E)-IPHC molecule by adopting both ab initio Hartree-Fock (HF) and DFT/B3LYP/6-
31+G(d,p) computational methods. Atoms in molecules (AIM), molecular electrostatic potential
(MEP), and HOMO-LUMO analysis were also computed for the (2E)-IPHC molecule. It is
thought that molecular characterization of the (2E)-IPHC compound will support the
development of improved anticonvulsant agents.
2. Experimental details
2.1. General
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The Fourier transform infrared spectrum of (2E)-IPHC molecule was recorded on a
Perkin Elmer RXL spectrometer (Waltham, Massachusetts, USA) in the region 4000-400 cm-1,
with sample in the KBr pellet method. The resolution of the spectrum is 2 cm-1. The FT-Raman
spectrum was measured in the range 3500-50 cm-1 using a Bruker RFS 100/S FT-Raman
spectrophotomer (Ettlingen, Germany.) with a 1064 nm Nd:YAG laser source of 100mW power
(Göttingen, Germany).
2.2. Synthesis
3-(1H-Imidazol-1-yl)-1-phenylpropan-1-one (0.86 gm, 4.3 mmol) was added to a suspension
containing anhydrous sodium acetate (0.35 gm, 4.3 mmol) and semicarbazide hydrochloride
(0.32, 4.3 mmol) in absolute ethanol (40 mL). The reaction mixture was stirred at ambient
temperature for 18 hrs, filtered and the filtrate was evaporated under vacuum. The residue was
crystallized from ethanol to give 0.44 gm (40%) of the title molecule m.p. (412-414 K) as white
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crystals which were suitable for X-ray analysis. H and C NMR as well as the mass spectral
data of the title compound 2 are consistent with the previously reported ones [10].
3. Quantum chemical calculations
The quantum chemical calculations have been performed with AM1, HF, and DFT
(B3LYP) methods using the Gaussian 03 program [14]. The minimum energy and optimized
structural parameters have been evaluated for the calculations of vibrational frequencies at
different levels of theories and variety of basis sets by assuming CS point group symmetry. At the
optimized geometry for the title molecule no imaginary frequency modes were obtained,
therefore a true minimum on the potential energy surface was found. As a result, the calculated
frequencies, reduced masses, force constants, infrared intensities, Raman intensities, and
depolarization ratios were obtained. In order to improve the calculated values, a spectral uniform
scaling factor was used to offset the systematic errors caused by basis set incompleteness,
neglect of electron correlation, and vibrational anharmonicity. Hence, the vibrational frequencies
were scaled by 0.9608 for B3LYP/6-31+G(d,p) [15]. After using the scaling factor, the deviation
from the experimental values was less than 10 cm-1 with a few exceptions. The Gaussview
program [16] has been employed to acquire visual animation and also for the verification of the
normal modes assignment. The potential energy distributions (PEDs) were computed from
quantum chemically calculated vibrational frequencies using the VEDA program [17].
The UV electronic absorption spectra are computed with time-dependent density
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functional theory (TD-DFT) at the B3LYP/6-31+G(d,p) level. Molecular electrostatic potential
(MEP) is used to investigate the binding and reactive centers of the title compound. The changes
in the thermodynamic functions (heat capacity, entropy, and enthalpy) are investigated at
different temperatures from that of the vibrational frequency calculations of the (2E)-IPHC
molecule. The NMR chemical shifts are computed with the gauge including atomic orbital
(GIAO) method using B3LYP/6-31+G(d,p). The HOMO-LUMO energy gap in different
solvents is computed and analyzed using the polarizable continuum model (PCM).
4. Results and discussion
4.1. Synthesis
The target molecule (2E)-IPHC (2) was synthesized as portrayed in Scheme 1 using the
commercially available acetophenone as a starting material according to our previously reported
procedure [10].
O
NH2
NH
O
N
O
N
i, ii
N
CH3
iii
N
N
1
2
Reagents and conditions: (i) HN(CH3)2ꢁHCl, (CH2O)n, conc. HCl, ethanol, reflux, 2 h; (ii) imidazole, water, reflux, 5 h;
(iii) semicarbazide hydrochloride, anhydrous sodium acetate, ethanol, RT, 18 hrs
Scheme 1: Preparation of the target compound 2.
4.2. Potential energy scan
A potential energy scan is mainly used to describe the relationship between potential energy
and molecular geometry. The conformational analysis was used through the potential surface
scan in order to determine the most optimized geometry of the (2E)-IPHC molecule. The
torsional barrier rotations are in reference to the C-N and C-C bonds. The first two potential
energy scan curves were carried out with dihedral angles C17–C18–N4–N5 and C17–C18–C19–
C22, the link between the phenyl ring with semicarbazide and imidazole moieties, respectively.
The third scan was carried out with dihedral angle C19-C18-N4-N5, the link between the
imidazole ring and the semicarbazide moiety. During the scan, all the geometrical parameters
were simultaneously relaxed and were varied in steps of 30° from 0 to 360°. The curves of the
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potential energy as a function of the dihedral angle were presented in Fig. 1. Thirteen conformers
were obtained in each scan. Conformational analysis revealed that the most stable conformer was
obtained in the third scan at a torsion angle of 180° with a global minimum energy of 81.1997
kcal/mol (0.129361 hartrees). After optimization with the global minimum energy, the phenyl
ring and semicarbazide moiety are in one plane and the imidazole ring is parallel to that plane.
The energies of the conformers of the (2E)-IPHC molecule were calculated by AM1 theory and
they are listed in Table 1. The standard deviations of the conformational energies were calculated
as 1.3929, 13.4253, and 10.9250 kcal/mol in scans 1, 2, and 3, respectively.
4.3. Molecular geometry structure details
The optimized molecular structure of the (2E)-IPHC molecule with the labeling of its
atoms is shown in Fig. 2. The selected bond distances and bond angles of XRD [18] and the
computed optimized geometrical parameters (HF and B3LYP) are presented in Table 2. The title
molecule is composed of phenylpropyl, imidazole, and semicarbazide moieties. All C–H
distances in the phenyl and imidazole rings showed similar values of about 0.930 Å, except for
the alkenes C–H bond lengths (0.970 Å). Among the C–H bond lengths, C19–H20 had the
maximum observed value. The C–N experimental bond distances in the semicarbazide and
imidazole moieties of the (2E)-IPHC molecule are very close to the values computed by HF and
B3LYP methods. The average values of the C-N single bond length in the semicarbazide and
imidazole moieties were calculated as 1.326 Å and 1.350 Å, respectively. The C31=O1 and
C18=N4 double bond were observed as 1.240 and 1.287 Å, respectively. The computed and
observed C=N bond length is shorter than C–N. The hexagonal symmetry of the phenyl ring in
the (2E)-IPHC molecule was distorted due to the differences in C-C bond values. The maximum
increase of C–C bond length was observed as 1.392 Å. It is also justified by the values of 1.391
Å and 1.405 Å computed by the HF and B3LYP methods, respectively. The experimental N–N
bond length was observed as 1.373 Å and its respective calculated value by both HF and B3LYP
methods was 1.392 Å. Three N–H bond distances for N5–H32, N6–H33 and N6–N34 were
observed in the semicarbazide moiety of the (2E)-IPHC molecule with the values of 0.829, 0.853
and 0.880 Å, respectively. The value of N6–34 was greater than the value of N6–N33 in the
amide group, which might be due to the intra-molecular attraction with the nearest oxygen atom.
The experimental bond angles in the phenyl ring showed an increase of bond angles C11–
C9–C7 (120.9) and C15–C13–C11 (120.4), and a decrease of bond angle C13–C11–C9 (119.1)
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from 120°. Variation of the C–C–C torsion angles from 120° in the phenyl ring are another
evidence of hexagonal symmetry distortion of the ring. The pulling effect of linking groups of
the phenyl ring was shown by the decrease of the dihedral angle C13–C11–C9 value by 0.9°
from 120°. The H–C–C torsion angles in the phenyl and imidazole rings were observed around
119° and 124°, respectively. Similarly, in the semicarbazide moiety the bond angles H34–N6–
H33, O1–C31–N6, N5–N4–C18, and N6–C31–N5 appeared as 115°, 123°, 119°, and 117°,
respectively.
4.4. Atoms in molecules (AIM) analysis
One of the most useful tools to characterize atomic and molecular interactions,
particularly hydrogen bonding, is topological analysis using ‘Atoms in molecules’ (AIM) theory
[19, 20]. AIM theory is used to understand and guess the electron density and nature of the bond
in complex molecules. According to AIM theory, any chemical bonding is characterized by the
existence of a bond critical point (BCP). The BCPs have been located and various properties can
be calculated at their coordinates in space. The AIM molecular graph showing the different
bonds and ring critical points of the (2E)-IPHC are depicted in Fig. 3 and the topological
parameters are given in Table 3.
The following parameters are based on the AIM theory as well as the Koch and Popelier
criteria [21]: (i) the presence of BCP between the proton (H) and acceptor (Y) is a confirmation
of the existence of a hydrogen bonding interaction; (ii) the value of the charge densities ρBCP of
C-C and C-N bonds are computed within the range of 0.2213–0.2956 and 0.2261–0.3329 a.u.
2
and the corresponding Laplacian ρBCP at BCP should be within the range -0.8724 to -0.5244
a.u and -0.7228 to -0.2852 a.u. In addition, the electron density minimum (0.0229 a.u) and
2
Laplacian ρBCP maximum (-0.0936 a.u) values were calculated in N4…H33 intermolecular
hydrogen bond. The terms GBCP, HBCP, and VBCP describe the electron kinetic energy density, total
electron energy density, and potential electron density, at BCP, respectively, while Eint describes
the interaction energy at bond critical points. The highest Eint interaction energy was observed at
the C=O bond as 260 kcal/mol. The lowest HBCP was calculated as -0.4876 a.u. The decrease in
HBCP was observed with an increase of Eint.. Similarly, Eint was calculated for C18=N4 as 225.24
kcal/mol and HBCP as -0.4289 a.u. along the same trend.
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4.5. Comparative Mulliken population analysis
Mulliken charge population of the (2E)-IPHC molecule was analyzed using the B3LYP
method with regard to its compositional groups: phenylpropyl, imidazole and semicarbazide.
The results are presented in Table 4. The horizontal bar diagram of comparative Mulliken atomic
charges are shown in Fig. 4. The comparison between the Mulliken charge distribution in the
intact (2E)-IPHC molecule and its separated phenylpropyl moiety indicated that the Mulliken
charge distribution is almost the same in the ring and the C17 is positive in both the (2E)-IPHC
molecule and the phenylpropyl moiety; whereas the atoms C18 and C19 exhibited some
deviation between the (2E)-IPHC molecule and the phenylpropyl moiety. This confirms an
influence of the attachment of the imidazole ring in the (2E)-IPHC molecule. Similarly, the
imidazole ring in the (2E)-IPHC molecule displayed deviation of Mulliken charges from that of
the separated imidazole moiety in the atoms N2, N3, C25, and C27. The atomic charge of C25 in
the (2E)-IPHC molecule is more positive as compared with that of the separated imidazole
moiety. Mulliken charge at the N4 (-0.279821 e) atom is less negative than at the N5 (-0.4771 e)
and N6 (-0.7571 e) atoms in the (2E)-IPHC molecule and they exhibited some deviation from
those values at the separated semicarbazide moiety. Atom C31 (0.736084 e) in the (2E)-IPHC
molecule was computed with the most positive charge due to its attachment to three
electronegative atoms, namely two nitrogen atoms and one oxygen atom. All hydrogen atoms in
the (2E)-IPHC molecule showed positive values and there was not much deviation in their
charge distribution as compared with that in the compositional groups. Mulliken charges at the
carbonyl and amide groups in the (2E)-IPHC molecule might contribute positively to its
biological activity.
4.6. Molecular electrostatic potential (MEP)
A 3D plot of molecular electrostatic potential (MEP) is used as a visual method to analyze
reactivity and relative polarity of atomic sites of molecules including biomolecules and drugs.
The MEPs of (2E)-IPHC were computed at HF and B3LYP levels (Fig. 5) based on their
optimized geometrical positions. The MEPs were computed to be between -0.06951 e and
0.06951 e in B3LYP and from -0.06166 e to 0.06166 e at the HF level.
The value of charges of MEP ranges from red (more negative) to blue (more positive). The
negative ion sites were observed near an oxygen atom (O1) in the semicarbazide moiety and
nitrogen atoms in the imidazole ring. Due to the electron withdrawing effect of O1, the nearby
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nitrogen atoms (N5 and N6) showed less negative potential. On the other hand, the positive ion
sites were observed around the phenyl ring and methylene groups. The negative charge of the
carbon atoms in the phenyl ring was diminished due to the effect of the other atoms attached to
the phenyl ring. The magnitude of MEP of all hydrogen atoms was positive. Both positive and
negative maxima were observed in the amide group, where the maximum positive value was
located at H34 and the maximum negative potential was shown at N6.
4.7. Thermodynamic simulation properties of (2E)-IPHC
Some of the statistical thermodynamic functions like entropy (S), enthalpy changes (δH)
and heat capacity (Cp) of (2E)-IPHC were simulated at the gas phase from the theoretical
harmonic frequencies and the results are listed in Table 5. It can be observed that these
thermodynamic functions increase with temperature over the range of 100 to 1000 K due to the
fact that the molecular vibrational intensities increase with temperature [22]. The computed
values of entropy and heat capacity attained the maximum and steady state was reached. The
enthalpy change increases linearly at low temperatures and abruptly at high temperature. The
correlation equations between entropy, enthalpy change, and heat capacity temperatures were
fitted by quadratic formulas and the corresponding fitting factors (R2) for these thermodynamic
properties all have the same value of 0.9999. The corresponding fit equations are as follows and
the correlation graph are displayed in Fig. 6.
B3LYP level
S=281.84267 +1.10322T−-2.40362x10−4 T2
H = -10.57948 + 0.11938T + 2.90332 x10 −5 T 2
(1)
δ
(2)
(3)
C=14.89099 +1.03651T−4.20155x10−4 T2
HF level
S=288.08499 +1.03061T− 2.14469x10−4 T2
(4)
δ
H = − 8.02599 + 0.10289 T + 2.8557 x10 −4 T 2
C=19.9219 +0.93787T−3.42113x10−4 T2
(5)
(6)
All of the simulated thermodynamic data are very helpful for further investigations on the
thermodynamic parameters of the (2E)-IPHC molecule. They can be used to compute the other
thermodynamic energies according to the relationships of thermodynamic functions, and
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estimate directions of chemical reactions according to the second law of.
4.8. Ultraviolet spectra analysis and Frontier molecular orbitals (FMOs)
The highest occupied molecular orbital (HOMO) and the lowest-lying unoccupied
molecular orbital (LUMO) are named as frontier molecular orbitals (FMOs). The Gauss-Sum 2.2
program [23,24] is used to calculate major and minor energy contributions to the molecular
orbitals. The energy gap between HOMO and LUMO determines the kinetic stability, chemical
reactivity, optical polarizability, and chemical hardness–softness of the molecule. Chemical
hardness and softness can be used as complementary tools in the description of the
thermodynamic aspects of chemical reactivity.
Molecular orbital energies are computed in the gas phase, ethanol, DMSO and acetonitrile.
The energies of the molecular orbital of the (2E)-IPHC molecule are calculated using B3LYP/6-
31+G(d,p) and the values are presented in Table 6. The computed HOMO and LUMO values in
the gas phase, ethanol, DMSO, and acetonitrile are -6.1147, -6.1133, -6.1141, -6.1139 and -
0.9812, -0.9801, -0.9809, -0.9807 eV, respectively. The energy gap between the HOMO and
LUMO was 5.1334 eV in the gas phase and 5.1331 eV in each of the solvents used.
The energy gap between HOMO–LUMO explains the eventual charge transfer interaction
within the molecule, which influences its biological activity. 3D plots of the HOMO and LUMO
orbitals computed at the B3LYP/6-31+G(d,p) level in the gas phase for the (2E)-IPHC molecule
are illustrated in Fig. 7. The orange color represents positive values while the green color
represents the negative values. In HOMO and LUMO, the lobes covered the phenyl ring and
semicarbazide moiety. The HOMO→LUMO transition implies an electron density transfer.
Electronegativity, chemical hardness, softness, and electrophilicity index of the compound
were computed in the gas phase at the B3LYP level and the values are 3.5479, 2.5667, 0.1948,
and 2.4521 eV, respectively. The dipole moment and self-consistent field (SCF) energy
convergence in the gas phase are 4.7124 Debye and -853.4065 hartrees, respectively. On the
other hand, DMSO showed the largest computed dipole moment value (4.6898 Debye) in the
liquid phase.
UV analysis of the (2E)-IPHC molecule has theoretically been investigated in the gas
phase, ethanol, DMSO, and acetonitrile solvents by TD-DFT/B3LYP/6-31+G(d,p) calculations.
Different solvents influence variable binding sites in compounds in distinct ways. The computed
values of electronic excitation energies, oscillator strengths and absorption wavelengths are listed
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in Table 7. The observed and simulated UV graphs are shown in Fig. 8. The computed
absorption values were found to be 267.06, 262.05, and 247.83 nm in the gas phase; 267.33,
262.30, and 247.89 nm in ethanol; 267.14, 262.74, and 247.87nm in DMSO; 267.21, 262.15, and
247.87 nm in acetonitrile. The experimental UV absorption maximum in acetonitrile was
observed at 275.52 nm. The major contributions of the transitions were designated with the aid
of the SWizard program [25]. In view of the absorption spectra, the maximum absorption
wavelength corresponds to the electronic transition from HOMO-1 to LUMO with 65%
contribution. The other wavelength, excitation energies, oscillator strength and calculated
counterparts with major contributions can be seen in Table 7.
4.9. Vibrational analysis
The observed vibrations are active with different shapes and intensities in Raman and
infrared. The title molecule has 34 atoms and with assumed Cs point group symmetry. The
vibrational modes were computed at the B3LYP level in the gas phase and were compared with
the experimental values and the calculated potential energy distributions (PED) as shown in
Table 8. The assignments of the observed wavenumbers from FT-IR and FT-Raman spectra were
based on the normal mode analyses. The observed and simulated FT-IR and FT-Raman spectra
of the (2E)-IPHC molecule are shown in Figs. 9 and 10, respectively.
Amide group vibrations
The amide group vibrations normally appear in the regions of 3550–3330 cm-1 and at 3450–
3250 cm-1 for asymmetric and symmetric stretching, respectively [26]. In the molecule under
study, there are three expected NH vibrations in the semicarbazide moiety. At this same position,
in the FT-IR, two NH asymmetric stretching vibrations were observed at 3463 and 3440 cm-1.
The single NH vibration was computed as 3392 cm-1 and it was assigned as symmetric
stretching. The observed and computed values are within the expected range. The NH2 scissoring
vibrations were found in the range of 3550–3330 cm-1. This mode of vibration was observed with
high intensity in the FT-Raman at 1560 cm-1 and the computed value was calculated as 1558 cm-
1. The PED was calculated as a mixed mode with in-plane bending C-H and its individual
contribution was computed as 72%. The single N-H in-plane bending was computed as 1413 cm-
1. One rocking NH2 vibration appeared at 1098 cm-1 with weak intensity in the FT-Raman
spectrum. The out-of-bending N-H modes were shown in the expected range. Most of the in-
plane and out-of-plane bending vibrations were computed with PED less than 50%.
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C-H vibrations
In the title compound, the C-H vibrations are due to the phenylpropyl and imidazol moieties.
Aromatic compounds commonly exhibit multiple weak bands in the region of 3100–3000 cm−1
due to aromatic C-H stretching vibrations. They are not appreciably affected by the nature of the
substituents [27]. Four aromatic, three imidazole, and four methylene C-H vibrations were
expected in the (2E)-IPHC molecule. The FT-IR band at 3150 cm-1 and FT-Raman bands at
3130, 3125, 3076, and 3066 cm-1 were observed and assigned as ring C-H stretching. Three
vibrations were observed at 2990, 2951, and 2938 cm-1 and were assigned to the methylene
groups in the (2E)-IPHC molecule. Their computed values were at 3007, 2988, 2952, and 2934
cm-1 with average PED of about 90%. The bands were observed with very weak intensities. The
in-plane bending modes of the phenyl ring of the (2E)-IPHC molecule appeared at 1482, 1460,
1444, and 1434 cm-1 and out-of-plane bending at 933, 906, and 830 cm-1. The PED values are in
the range of 61–97%.
The computed values of the imidazole ring in-plane bending modes of the title compound are
presented at 1373, 1354, and 1262 cm-1 and out-of-plane bending at 770, 776, and 688 cm-1. The
CH2 scissoring vibrations were computed as 1373 and 1354 cm-1. A vibration was observed in
the FT-IR at 1342 cm-1 with strong intensity and was assigned as CH2 scissoring. A NH2 rocking
vibration was calculated at 1274 and 1269 cm-1 and the observed band was found at 1275 cm-1 in
FT-Raman. The CH2 twisting and wagging were found in the anticipated range.
C=O vibrations
The C=O stretching and the NH2 scissoring deformation vibrations overlap each other in
the hydrogen-bonded state. The C=O stretch is the stronger band in the infrared and absorbs
usually in the range of 1680–1640 cm-1. Similarly, C=O stretching overlapped with N-H, and N-
H stretching appeared around 3300 cm-1 [28]. In the FT-IR spectrum of (2E)-IPHC, a very strong
band was found at 1690 cm-1 and was assigned to the C=O stretching type of vibration. The N-
C=O in-plane bending deformation normally appears at 600–550 cm-1. In the present
investigation, it appeared at 538 cm-1 in FT-Raman with medium intensity. The calculated value
is presented at 534 cm-1 with PED value 46%.
C-C vibrations
Aromatic C=C stretching modes occur in the region of 1620–1400 cm-1 and it is called ring
mode. C=C and C=O bonds interact strongly in the same region because the masses of carbon
11

ACCEPTED MANUSCRIPT
and oxygen atoms do not differ greatly. The bands in the range of 1650–1400 cm-1 were assigned
to the C=C stretching mode [29,30]. The C=C stretching vibrations were found at 1590, 1576,
and 1501 cm−1 and the C–C stretching vibrations were observed at 1285, 1247, and 1145 cm−1.
All bands appeared with strong and medium intensities in both FT-IR and FT-Raman. The
computed values fit well with the observed values and appeared in the expected range. The
imidazole ring C-C stretching vibration was observed at 1019 cm−1 with weak intensity in the
FT-Raman spectrum. The PED values for C=C bonds are 60–64% and for C–C bonds are 30–
35%. The aromatic in-plane CCC bending vibrations were obtained at 970 and 705 cm−1 in the
FT-IR spectrum, while the CCC out-of-plane bending vibrations were observed at 675 and 585
cm−1 in the FT-Raman and FT-IR spectra of the (2E)-IPHC molecule. The vibrations were
observed with strong and medium intensities which is reflected in the PED around the range of
24–58%.
C=N, C-N and N=N vibrations
Compounds containing a C=N group are characterized by the C=N stretching band in the FT-
IR and FT-Raman spectra. However, the C=N stretching frequency is expected to be phase-
sensitive, since the C=N moiety is a polar functionality. The C–N stretching absorptions appear
in the region of 1382–1266 cm-1 for aromatic amines [31,32]. The infrared band of the C=N
stretching mode is often found between those of the C=O and C=C stretching modes. Medium
intensity bands were observed at 1602 and 1613 cm-1 in the FT-IR and FT-Raman spectra,
respectively, of the title molecule and they were assigned as the C=N stretching vibrations. The
in-plane bending of the C=N vibration was observed at 630 cm-1 in the FT-IR spectrum of the
(2E)-IPHC molecule.
The C-N stretching vibrations are usually mixed with other vibrations and are difficult to
identify in the spectrum. Seven C-N stretching modes are expected to be observed in the (2E)-
IPHC molecule. Three stretching modes were identified at 1330, 1104, and 1008 cm-1
(imidazole) in addition to one C-N stretching mode at 1360 cm-1 (semicarbazide) with a very
weak intensity in the FT-Raman spectrum of the (2E)-IPHC molecule. The in-plane and out-of-
plane bending modes of C-N vibrations were found in the expected range.
N-N stretching vibration appeared at 1128 cm-1 with a very weak intensity in the FT-Raman
spectrum of the (2E)-IPHC molecule. While, the computed FT-Raman in-plane and out-of-plane
bending were found at 770 and 67 cm-1 with PED values of 66 and 46%, respectively.
12

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4.10. NMR analysis
Nuclear magnetic resonance (NMR) is an important analytical tool to elucidate the
13
chemical structure of organic compounds. The experimental NMR (1H and C) spectra were
analyzed and fit to the correct values with the aid of computed calculations. The experimental
and simulated proton and carbon NMR of (2E)-IPHC are shown in Fig. 11. The observed and
computed NMR (2E)-IPHC chemical shifts are given in Table 9. The NMR chemical shifts were
computed in DMSO and acetonitrile solvents and were compared with observed values. In the
13C NMR spectrum, the signal at 145.1 ppm was assigned to be due to C31 bonding with the
oxygen (O1) atom. Similarly, the peak at 153.6 ppm was assigned to the C18 double bond to the
nitrogen atom. The 13C NMR of the phenyl ring in the (2E)-IPHC molecule was observed
between 128.4 and 136.8 ppm. The chemical shifts of the imidazole ring carbons were also found
in the range of 119.4–137.3 ppm. The chemical shifts of methylene carbon atoms C19 and C22
were predicated with the lowest carbon chemical shifts of 37.4 and 47.0 ppm, respectively.
In the 1H NMR spectrum of (2E)-IPHC, eleven peaks were observed between 3.34 and 8.89
ppm. The proton NMR chemical shift signal splitting is caused by spin-spin coupling between
nearest nuclei. The 1H NMR signals of methylene protons in the side chain were observed at 3.34
and 4.13 ppm, which were assigned to be due to the equivalent protons H20, H21 and H23 and
H24 atoms, respectively. The phenyl ring protons appeared in the range of 7.06 to 7.85 ppm. A
1
similar trend was observed in the imidazole ring protons, the H NMR of H26 appeared at 6.87
ppm and the remaining H28 and H30 atoms appeared at 7.29 and 7.65 ppm, respectively.
The correlations between the experimental and computed chemical shifts were obtained by
the B3LYP method in DMSO and acetonitrile. The relations between the computed and
experimental carbon and hydrogen chemical shifts are linear and described by the following
equations:
13C NMR
δcal (ppm) = 1.06487 δexp + 1.0123 (R2 = 0.9920) in DMSO
δcal (ppm) = 1.07725 δexp + 1.0122 (R2 = 0.9921) in acetonitrile
(7)
(8)
1H NMR
δcal (ppm) = -0.44728 δexp + 1.1627 (R2 = 0.8588) in DMSO
δcal (ppm) = -0.45375 δexp + 1.1633 (R2 = 0.8590) in acetonitrile
(9)
(10)
13

ACCEPTED MANUSCRIPT
1
13
The calculated chemical shift values for both H and C NMR showed good linear fitting
with the experimental values according to the regression values (0.86–0.99).
5. Conclusions
The potential energy scan of the anticonvulsant agent named (2E)-2-[3-(1H-imidazol-1-yl)-1-
phenylpropylidene]hydrazinecarboxamide ((2E)-IPHC) was used to identify the most stable
conformer with the global minimum energy. The investigations of the optimized molecular
geometry showed that there was a considerable change in the bond lengths (CH, CC, CN, and
CO) and bond angles (CCC, CCN, HNN, NCC, and HNC) between the phenylpropyl,
semicarbazide, and imidazole moieties of the (2E)-IPHC molecule but they deviate less from the
experimental values. In the AIM analysis, the interaction energy and total electron density
variation, charge density range and Laplacian charge density range were analyzed. All hydrogen
atoms in the (2E)-IPHC molecule exhibited positive values and there was not much deviation in
charge distribution. Mulliken charges in the carbonyl and amide groups could contribute
positively to the displayed biological activity of the title molecule. In view of the calculated
absorption spectra, the maximum absorption wavelength corresponds to the electronic transition
from HOMO-1 to LUMO with a 65% contribution. Most of the amino group in-plane and out-of-
plane bending vibrations were computed with PED less than 50%. The twisting and wagging of
the methylene group were found in the anticipated range. The infrared band of the C=N
stretching mode was found between those of the C=O and C=C stretching modes. The computed
1
13
values for both H and C NMR showed good linear fitting with the experimental values as
evidenced by the regression values around 0.90.
Acknowledgments
The authors would like to extend their sincere appreciation to the Deanship of Scientific
Research at King Saud University for its funding of this research through the Research Group
Project No. RGP-VPP-196.
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Figure legends
Scheme 1: Preparation of the target compound 2.
Figure 1: Potential energy scan of (2E)-IPHC.
Figure 2: Optimized geometric structures with atoms numbering of (2E)-IPHC.
Figure 3: AIM molecular graph of (2E)-IPHC.
Figure 4: Comparative Mulliken charge distribution of (2E)-IPHC.
Figure 5: Molecular electrostatic potential (MEP) map in gas phase of (2E)-IPHC.
Figure 6: Correlation graph of thermodynamic functions with temperature of (2E)-IPHC.
Figure 7: Molecular orbitals and energies for the HOMO and LUMO of (2E)-IPHC in the gas
phase.
Figure 8: Experimental and simulated UV spectra of (2E)-IPHC.
Figure 9: Experimental and simulated Infrared spectra of (2E)-IPHC.
Figure 10: Experimental and simulated Raman spectra of (2E)-IPHC.
Figure 11:
The simulated (upper) and experimental (lower) proton and carbon NMR spectra
of (2E)-IPHC.
17

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Table 1: Potential energy scan values of (2E)-IPHC
.
Scan 1 C17-C18-N4-N5
Scan 2 C17-C18-C19-C22 Scan 3 C19-C18-N4-N5
Initial
Energy
Dihedral
(kcal/mol)
angle
Initial
Dihedral
angle
Initial
Dihedral
angle
3
Energy
(kcal/mol)
Energy
(kcal/mol)
92.7459
94.7539
96.1344
96.9502
96.0717
93.5616
92.8714
93.4361
93.6244
94.0009
94.6911
93.4361
92.7459
81.6389
87.4748
103.0998
126.2549
94.8794
85.6550
82.2037
85.4040
94.8166
110.8182
100.8408
85.7178
81.2624
81.6389
85.5923
98.9582
111.696
98.4562
86.2198
82.2037
87.0355
101.2173
111.6339
96.3227
84.5882
81.1997
72
178
33
63
93
102
132
162
192
222
252
282
312
342
372
402
432
208
238
268
298
328
358
388
418
448
478
508
538
123
153
183
213
243
273
303
333
363

ACCEPTED MANUSCRIPT
Table 2: Selected optimized parameters of (2E)-IPHC
.
Bond length
N5H32
N6H33
N6H34
C7H8
B3LYP HF
1.017 0.996
1.010 0.991
1.008 0.991
1.087 1.076
1.086 1.075
1.086 1.075
1.086 1.075
1.087 1.076
1.080 1.069
1.082 1.070
1.083 1.072
1.098 1.086
1.094 1.083
1.094 1.083
1.095 1.084
1.222 1.201
1.291 1.260
1.315 1.290
1.373 1.351
1.394 1.384
1.396 1.386
1.396 1.385
1.395 1.385
1.405 1.391
1.369 1.350
1.367 1.349
1.377 1.369
1.401 1.376
1.357 1.352
1.495 1.447
1.456 1.501
1.513 1.512
1.543 1.533
Experimental a Bond angle
B3LYP HF
121.5
Experimentala
125.7
118.2
115.0
119.7
119.5
120.5
119.8
119.3
124.7
124.7
123.6
108.9
107.4
108.9
107.7
123.6
123.9
120.9
119.1
120.4
119.7
117.5
110.6
106.4
118.7
119.2
120.8
125.9
115.6
113.5
0.829
0.853
0.853
0.930
0.930
0.930
0.930
0.930
0.930
0930
H32N5N4
121.7
118.5
119.0
119.6
119.7
120.1
119.6
119.7
132.6
121.3
125.9
108.1
107.5
107.6
107.4
125.4
116.2
120.2
119.7
120.2
120.4
114.5
110.7
106.2
121.2
120.6
118.5
126.7
112.3
112.7
H33N6C31
H34N6H33
H8C7C9
120.9
120.4
119.6
119.8
120.1
119.7
119.8
132.0
121.6
125.4
108.5
107.7
107.8
107.4
124.2
117.0
120.1
119.8
120.1
120.2
115.8
110.3
105.1
121.1
120.7
118.0
126.9
112.2
112.4
C9H10
C11H12
C13H14
C15H16
C25H26
C27H28
C29H30
C19H20
C19H21
C22H23
C22H24
C31O1
C18N4
C29N4
C27C25
C9C7
H10C9C7
H12C11C9
H14C13C15
H16C15C13
H26C25C27
H28C27N3
H30C29N3
H20C19C22
H21C19H20
H23C22N2
H24C22H23
O1C31N6
0930
0.970
0.970
0.970
0.970
1.240
1.287
1.366
1.349
1.380
1.375
1.369
1.383
1.392
1.371
1.332
1.313
1.369
1.373
1.486
1.460
1.509
1.529
N4C18C19
C11C9C7
C13C11C9
C15C13C11
C7C17C18
N6C31N5
C11C9
C13C11
C15C13
C7C17
C29N2
C31N6
C27N3
C31N5
N4N5
C25C27N3
C27N3C29
C31N5N4
N5N4C18
C17C18C19
C22N2C29
C18C19C22
C19C22N2
C17C18
C22N2
C18C19
C19C22
aRef [18]

ACCEPTED MANUSCRIPT
Table 3: AIM analysis for the (2E)-IPHC molecule: electron density ρBCP, Laplacian
of electron density ∆2ρBCP, electron kinetic energy density GBCP, total
electron energy density HBCP and interaction energy Eint at bond critical
points (BCPs).
BCP
GBCP
(a.u)
HBCP
(a.u)
VBCP
(a.u)
Eint
(kcal/mol)
128.57
133.21
132.65
132.40
133.37
129.57
89.29
ρBCP
(a.u)
∆2ρBCP
(a.u)
C17-C15
C15-C13
C13-C11
C11-C9
C9-C7
C7-C17
C11-H12
C17-C18
C18-C19
C19-C22
N4-N5
C31-N6
C18-N4
C22-N2
C29-N2
C29-N3
C27-N3
C25-N2
C25-C27
C31-O1
N4…..H33
C27-H28
C22-H24
0.2284
0.2954
0.2949
0.2946
0.2956
0.2900
0.2669
0.2471
0.2359
0.2213
0.2944
0.2972
0.3329
0.2261
0.2717
0.3276
0.2737
0.2625
0.3073
0.3700
0.0229
0.2707
0.2654
-0.8328
-0.8712
-0.8716
-0.8700
-0.8724
-0.8400
-0.7920
-0.6488
-0.5896
-0.5244
-0.4272
-0.6068
-0.5596
-0.2852
-0.3924
-0.7228
-0.4648
-0.3520
-0.8856
-0.5744
-0.0936
-0.8120
-0.7828
0.1008
0.1034
0.1024
0.1022
0.1035
0.1015
0.0434
0.0715
0.0676
0.0595
0.1545
0.1582
0.2890
0.1194
0.1860
0.1896
0.1418
0.1809
0.1208
0.3439
0.0228
0.0422
0.0427
-0.3090
-0.3212
-0.3204
-0.3198
-0.3216
-0.3115
-0.2413
-0.2337
-0.2150
-0.1906
-0.2613
-0.3098
-0.4289
-0.1908
-0.2741
-0.3703
-0.2580
-0.2671
-0.3422
-0.4876
-0.0006
0.2454
0.2383
0.4098
0.4246
0.4228
0.4220
0.4251
0.4130
0.2846
0.3052
0.2827
0.2501
0.4158
0.4680
0.7179
0.3102
0.4701
0.5600
0.3999
0.4501
0.4630
0.8315
0.0221
0.2877
0.2811
95.75
88.69
78.46
130.45
146.83
225.24
97.32
147.49
175.70
125.46
141.21
145.26
260.88
6.93
90.26
88.19

ACCEPTED MANUSCRIPT
Table 4: Comparative Mulliken charges of (2E)-IPHC and its compositional groups;
phenylpropyl, semicarbazide and imidazole.
Atom
O1
N2
N3
N4
N5
N6
C7
H8
(2E)-IPHC
-0.520550
-0.365862
-0.435363
-0.279821
-0.477195
-0.757188
-0.168459
0.144444
-0.131064
0.143965
-0.122304
0.143447
-0.128822
0.145912
-0.183791
0.158293
0.069557
- 0.215524
-0.317504
0.161568
0.168236
-0.163087
0.171220
0.171646
0.003864
0.147826
-0.037504
0.133974
0.191298
0.149358
0.736084
0.338202
0.350224
0.343871
Phenylpropyl Semicarbazide
-0.535134
Imidazole
-0.611397
-0.558599
-0.590508
-0.456057
-0.729375
-0.175101
0.123932
-0.137724
0.126097
-0.129500
0.124634
-0.129130
0.126092
-0.181223
0.121014
C9
H10
C11
H12
C13
H14
C15
H16
C17
C18
C19
H20
H21
C22
H23
H24
C25
H26
C27
H28
C29
H30
C31
H32
H33
H34
0.160162
-0.321438
-0.293246
0.153945
0.142429
-0.312067
0.154951
0.144400
-0.019444
0.136170
0.035829
0.142275
0.115053
0.122198
0.666378
0.345970
0.313127
0.364071

ACCEPTED MANUSCRIPT
Table 5: Thermodynamic functions at different temperatures at B3LYP and HF level
of (2E)-IPHC.
S (J/mol.K)
Cp (J/mol.K)
ddH (kJ/mol)
Temperature
(K)
B3LYP
HF
B3LYP
HF
B3LYP
HF
100
200
298
300
400
500
600
700
387.91
495.49
589.59
591.33
683.91
772.88
857.17
936.33
1010.47
385.30
489.42
577.57
579.19
665.35
748.68
828.36
903.82
974.96
124.51
197.20
280.47
282.06
363.96
433.78
490.46
536.26
573.76
604.94
631.20
122.74
186.85
260.96
262.42
339.47
408.19
465.70
513.05
552.22
585.02
612.79
8.62
24.55
47.96
48.48
8.51
23.90
45.81
46.29
76.43
113.90
157.69
206.70
260.03
316.94
376.86
80.86
120.86
167.17
218.59
274.15
333.13
394.97
800
900
1000
1079.90 1041.95
1145.04 1105.07

ACCEPTED MANUSCRIPT
Table 6: Calculated molecular orbital energies values of (2E)-IPHC.
GAS
Ethanol
-6.2283
-6.1133
-0.9801
-0.1515
-5.1331
-6.0767
3.5467
2.5666
0.1948
2.4505
4.6419
DMSO
-6.2321
-6.1141
-0.9809
-0.1545
-5.1331
-6.0775
3.5475
2.5666
0.1948
2.4516
4.6898
Acetonitrile
-6.2307
-6.1139
-0.9807
-0.1534
-5.1331
-6.0773
3.5473
TD-DFT/B3LYP/6-31+G(d,p)
HOMO-1
HOMO
LUMO
LUMO+1
-6.2340
-6.1147
-0.9812
-0.1559
-5.1334
-6.0781
3.5479
2.5667
0.1948
2.4521
4.7124
HOMO-LUMO
HOMO-1 – LUMO+1
Electronegativity (χ)
Chemical hardness (η)
Softness (S)
Electrophilicity index (ω)
Dipole moment (Debye)
SCF Energy (hartrees)
2.5666
0.1948
2.4513
4.6726
- 853.4065 -853.4056 -853.4062
-853.4060

ACCEPTED MANUSCRIPT
Table 7: Computed excitation energies E (eV), absorption wavelength λ (nm), and
oscillator strengths (f) using TD-DFT/B3LYP/6-31+G(d,p) method for (2E)-
IPHC.
Energy Wavelength
Oscillator
strength
0.0006
0.5451
0.0009
Major contribution of
energy
HOMO-1->LUMO (99%)
HOMO->LUMO (96%)
HOMO-2->LUMO (55%)
Medium
GAS
(eV)
(nm)
4.6425
4.7312
5.0026
267.06
262.05
247.83
Ethanol
DMSO
4.6378
4.7267
5.0014
267.33
262.30
247.89
0.0006
0.5507
0.0009
HOMO-1->LUMO (99%)
HOMO->LUMO (96%)
HOMO-2->LUMO (55%),
4.6410
4.7188
5.0019
267.14
262.74
247.87
0.0006
0.5624
0.0009
HOMO-1->LUMO (99%)
HOMO->LUMO (96%)
HOMO-2->LUMO (55%)
Acetonitrile 4.6399
4.7294
267.21
262.15
247.87
0.0006
0.5473
0.0009
HOMO-1->LUMO (99%)
HOMO->LUMO (96%)
HOMO-2->LUMO (55%)
5.0019

ACCEPTED MANUSCRIPT
Table 8: Detailed assignments of theoretical wavenumbers of (2E)-IPHC.
Experimental wavenumbersa
B3LYP/6-31G(d,p) wavenumbers
Mode descriptionb
FT-IR
3463 vw
3440 m
3395 vw
3150 m
3130 vw
FT-Raman Unscaled scaled
IIR
2.15
2.26
0.07
0.42
0.70
1.13
4.27
1.05
0.59
SRaman
1.67 γNH(98)
3724
3594
3533
3286
3259
3255
3217
3208
3201
3193
3188
3133
3113
3075
3057
1833
1681
1659
1633
1623
1559
1547
1542
1520
1503
1493
1471
1430
1419
1410
1401
1370
1339
1327
1322
1314
1295
1271
3575
3451
3392
3155
3129
3125
3088
3079
3073
3065
3060
3007
2988
2952
2934
1760
1614
1592
1568
1558
1496
1485
1480
1459
1443
1433
1413
1373
1362
1354
1345
1315
1285
1274
1269
1262
1243
1220
2.12 γNH(98)
9.37 γNH(100)
2.34 γCH(99)
1.62 γCH(97)
5.09 γCH(96)
2.51 γCH(90)
2.19 γCH(94)
1.44 γCH(90)
5.21 γCH(93)
1.11 γCH(92)
4.09 γCH(91)
2.55 γCH(87)
2.27 γCH(87)
0.75 γCH(94)
3.58 γC=O(73)
5.19 γC=N(77)
2.15 γCC(63)+βCH(19)
0.61 γCC(65)+βCH(11)
2.24 βNH(72)+βCH(10)
3.53 γCC(62)+βCH(17)
1.71 γCC(24)+βCH(65)
5.13 γCC(56)+ βCH(16)
9.01 βCH(67)
3130 vw
3125 vw
3076 vw
3066 vw
1.81
1.18
8.87
3.03
2990 vw
2938 vw
2951 w
1.25
13.53
126.80
97.77
6.69
1690 s
1602 m
1613 m
1590 vs
1576 s
7.06
1560 s
1501 s
23.18
43.87
47.77
43.24
4.71
1482 vw
1460 vw
1444 s
9.67
5.66
4.21 βCH(61)
1434 vw
1360 vw
3.51 βCH(68) +γCC(28)
1.21 βCH(44) +γCN(16)
4.69 βCH(38) +γCC(20)
0.15 γCN(34)
1.16
φC=N(50)
1.49 γCN(53)
1.03 βCH(70)+γCC(14)
1.65 βCH(61)+γCC(10)
3.28 βCH(46)
1.09 βCH(25)+βCN(11
0.89 βCH(27)+γCC(12)
3.33 γCC(34)
30.53
5.20
15.65
28.56
16.34
8.56
21.99
11.20
22.89
11.52
12.28
2.53
1342 m
1330 vw
1319 m
1285 m
1275 m
1247 m
1228 m
1.16 βCN(57)+γCN(11)

ACCEPTED MANUSCRIPT
1170 m
1145m
1104 m
1069 m
1218
1197
1195
1173
1151
1142
1112
1104
1096
1056
1051
1039
1028
1017
1005
981
1169
1149
1147
1126
1104
1096
1067
1060
1052
1014
1009
997
0.57
12.72
2.49
0.54
3.58
0.23
3.44
7.69
5.70
39.68
4.80
28.96
35.47
20.53
9.88
6.77 βCH(76)+γCC(11)
3.20 βCH(81)+γCC(13)
2.19 βCH(32)+γNN(14)
1.05 γNN(41)
5.84 γCN(44)+βCH(28)
0.17 βNH(34)+γCC(13)
29.66 γCC(40)+βCH(32)
30.11 βCH(47)+γCC(14)
7.64 γCC(20)+βCN(15)
1.41 γCC(37)+βCCC(23)
18.96 βCN(19)+γCN(16)
5.15 γCN(20)+βCN(10)
10.23 γCC(61)
1128 vw
1098 vw
1062 vw
1049 w
1019 w
1008 m
987
976
970 w
1.05
φCCC(56)+ γCC(25)
φCH(77)+φCCC(14)
964
12.55
942
938
13.71
68.84
76.52
0.06
6.98 γCN(73)
933 m
906 m
978
8.10
φCH(82)+φCCC(11)
φCH(89)
942
904
22.45
915
879
5.38 βCCN(79)
830 w
868
833
1.33
5.46
8.50
φCH(97)
851
817
37.51
54.59
49.52
20.00
12.26
17.98
3.49
φHCN(80)
φCH(24)+βCCN(10)
φHCN(66)
φCH(42)
817
784
27.17
18.14
36.10
5.87
802
770
765 s
801
767
758
728
φCH(36)
751
720
10.51
1.51
φCON(55)
φCON(35)
φCH(80
705 m
743
714
717
688
5.07
18.14
59.19
675 m
640 m
717
688
13.73
φCCC(44)+
φCH(33)
676
649
233.16
6.71
φCCC(76)+
φCH(10)
630 m
654
652
628
626
1.52
12.52
φNCC(21)
200.07
2.07 βCCN(58)+
φCCNC(13)
633
625
607
600
36.47
51.91
5.10 βCCC(58)+
φCCNC(23)
21.42
φCCNC(33)+
βCCC(19)
585 w
614
580
589
557
14.23
3.87
1.98
2.75
φCCN(48)
φHNNC(66)+φHNC
N(12)

ACCEPTED MANUSCRIPT
538 m
556
534
42.22
7.05
2.24
βNCO(46)+φHNCN
(14)
489 m
501
481
29.12
φHNCN(53)+βNCO
(13)
485
461
466
443
325.28
2.42
20.11 βCCN(31)
441 vw
17.89
φCCCC(41)
βCCN(12)
398 vw
412
395
0.90
109.60
φCCCC(68)+
φHCCC (17)
φCCNN(58)
φHNCN(60)
393
370
356
378
356
342
29.42
471.74
5.25
334.79
34.25
342 vw
95.88 βCCN(46)+
φHNCN(10)
310
295
254
215
181
133
298
283
244
207
174
128
29.63
0.85
20.20
2.47
0.15
9.01
25.18 βCNCN(31)
79.54 βCCCN(28)
3.41 βCCCN(31)
14.24 βCCCC(44)
243 vw
215 vw
165 vw
121 m
95.96
φCCNN(49)
88.40 βCCCC(25)+
φCCNC(13)
93 w
93
70
69
62
47
40
28
25
89
67
66
60
45
38
26
24
23.14
15.29
4.95
26.79
304.89
38.63
φCCNC(34)
φNCNN(46)
φCCCC(45)
φCCCN(51)
φCCCC(48)
φCCCC(67)
φCCCC(53)
φCCCN(27)
6.05
118.46
90.49
3.66
17.76
28.44
76.73
110.02
140.52
68.36
a s: strong; vs: very strong; m: medium; w: weak; vw: very weak. b ν: stretching; β: in-
plane bending; γ: out-of-plane bending; IIR: IR intensity, SRaman: Raman scattering
activity

ACCEPTED MANUSCRIPT
Table 9: Experimental, calculated (corrected) 13C and 1H NMR isotropic chemical
shifts (ppm) of (2E)-IPHC.
13C
1H
δcal (B3LYP)
δcal (B3LYP)
Atom δexp
Atom
δexp
DMSO
Acetonitrile
125.1
127.2
127.2
123.9
135.9
145.1
159.2
37.4
DMSO
7.58
7.36
7.15
7.20
7.75
2.95
2.13
3.61
3.36
6.72
6.74
7.29
8.75
4.99
3.84
Acetonitrile
7.57
7.36
7.15
7.20
7.74
2.95
2.13
3.60
3.35
6.72
6.74
7.29
C7
C9
129.4 125.1
128.4 127.2
128.5 127.2
128.4 123.9
129.4 135.9
136.8 145.1
153.6 159.2
H8
7.85
7.34
7.06
7.34
7.85
3.34
3.34
4.13
4.13
6.87
7.29
7.65
8.89
7.40
7.40
H10
H12
H14
H16
H20
H21
H23
H24
H26
H28
H30
H32
H33
H34
C11
C13
C15
C17
C18
C19
C22
C25
C27
C29
C31
28.3
42.1
37.4
47.0
47.0
119.4 114.9
119.9 127.3
137.3 131.4
145.1 151.9
114.9
127.4
131.4
151.8
8.74
4.99
3.83