Synthesis, structural exploration, spectral and combinatorial analysis of racemic-3-isobutyl-5-phenyl-5-(pyridin-4-yl)imida-zolidine-2,4-dione: Comparison between experimental and DFT calculations

Article abstract of DOI:10.1016/j.molstruc.2018.04.096

New racemic 3-isobutyl-5-phenyl-5-(pyridin-4-yl)imidazolidine-2,4-dione was synthesized, isolated, characterized spectrally, thermally and finally the structure was confirmed by X-ray diffraction studies. Both XRD and DFT/B3LYP/6-31G(d,p) optimized structures of the compound revealed the diketo monomer as favored tautomer isomer structure. The molecular geometry optimization parameters were compared with the experimental XRD results. The electronic spectrum which allocated basis of the TD-SCF result and the MO energy level diagram were compared with the experimental one. The electrophilic and nucleophilic receptors and acceptor functional groups with their interactions on the molecule surface was established by packing diagrams and then compared with Hirshfeld surface, electrostatic potential map and Mullikan population theoretical calculations. The experimental ¹H NMR results, compared to the theoretical ACD-lab and NMR-db showed an excellent agreement. The desired organic compound revealed a high thermal stability in an open atmosphere.

Full text of DOI:10.1016/j.molstruc.2018.04.096

Accepted Manuscript
Synthesis, structural exploration, spectral and combinatorial analysis of racemic-3-
isobutyl-5-phenyl-5-(pyridin-4-yl)imida-zolidine-2,4-dione: Comparison between
experimental and DFT calculations
S.B. Benaka Prasad, S. Naveen, C.S. Ananda Kumar, N.K. Lokanath, A.V. Raghu,
Iqab Daraghmeh, Kakarla Raghava Reddy, Ismail Warad
PII:
S0022-2860(18)30548-9
10.1016/j.molstruc.2018.04.096
MOLSTR 25169
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 24 January 2018
Revised Date: 27 April 2018
Accepted Date: 30 April 2018
Please cite this article as: S.B. Benaka Prasad, S. Naveen, C.S. Ananda Kumar, N.K. Lokanath,
A.V. Raghu, I. Daraghmeh, K.R. Reddy, I. Warad, Synthesis, structural exploration, spectral and
combinatorial analysis of racemic-3-isobutyl-5-phenyl-5-(pyridin-4-yl)imida-zolidine-2,4-dione:
Comparison between experimental and DFT calculations, Journal of Molecular Structure (2018), doi:
10.1016/j.molstruc.2018.04.096.
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ACCEPTED MANUSCRIPT
Synthesis, structural exploration, spectral and combinatorial analysis of racemic-3-
isobutyl-5-phenyl-5-(pyridin-4-yl)imida-zolidine-2,4-dione: Comparison between
experimental and DFT calculations
Benaka Prasad S. B.1, Naveen S.1*, Ananda Kumar C. S.2,3, Lokanath N. K.4, Raghu A. V.1,
Iqab Daraghmeh5, Kakarla Raghava Reddy,6 Ismail Warad7*
1Department of Basic Sciences, School of Engineering and Technology, Jain University, Bangalore 562
112, India
2Department of Nanotechnology, Visvesvaraya Technological University, CPGS, Muddenahalli,
Bengaluru region - 562101, India.
3Centre for Materials Science, Vijnana Bhavan, University of Mysore, Manasagangotri, Mysore - 570
006, India.
4Department of Studies in Physics, University of Mysore, Manasagangotri, Mysore - 570 006, India
5Department of Chemistry, Arab American University-Jenin, P.O. Box 240, Jenin, Palestine
6 The School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney, NSW 2006,
Australia.
7Department of Chemistry, Science College, An-Najah National University, P.O. Box 7, Nablus, Palestine
Address for Correspondence: s.naveen@jainuniversity.ac.in; Tel./Fax: +91 80 27577199,
warad@najah.edu; Tel./Fax: +970-9234-5982.
Abstract:
New racemic 3-isobutyl-5-phenyl-5-(pyridin-4-yl)imidazolidine-2,4-dione was synthesized,
isolated, characterized spectrally, thermally and finally the structure was confirmed by X-ray
diffraction studies. Both XRD and DFT/B3LYP/6-31G(d,p) optimized structures of the
compound revealed the diketo monomer as favored tautomer isomer structure. The molecular
geometry optimization parameters were compared with the experimental XRD results. The
electronic spectrum which allocated basis of the TD-SCF result and the MO energy level
diagram were compared with the experimental one. The electrophilic and nucleophilic receptors
and acceptor functional groups with their interactions on the molecule surface was established by
packing diagrams and then compared with Hirshfeld surface, electrostatic potential map and
Mullikan population theoretical calculations. The experimental 1H-NMR results, compared to the
theoretical ACD-lab and NMR-db showed an excellent agreement. The desired organic
compound revealed a high thermal stability in an open atmosphere.
Keywords: Condensation, XRD, Crystal structure, Hirshfeld surface, DFT-computation.

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1. Introduction
Since imidazolidine-2,4-dione was found by Bayer, a huge number of imidazolidines with their
derivatives were prepared by several synthesized methods mostly for their medical applications
[1-4]. Imidazolidines are used in several biological activities like: anti-epileptic, anti-arrythmic,
anti-schistosomal, tuberculostatic, anti-tumor, trematodeos, anti-bacterial, herbicides and
fungicidal drugs [5-7]. The composite importance of imidazolidines came from their different
structural features, since these compounds contain both acceptors and donor groups in their
backbones. Two ring NH functional groups act as a source of H-bonds donor while the two
carbonyl functional groups behave as H-bonds acceptors offering extra structure-stability and
activity, which may lead to the diversification and expansion on biological activities of
imidazolidines [8-10]. Much X-ray crystal structure analysis succeeded in conformation of H-
bonding interaction in imidazolidines which explained their dimers naturally [10-11]. Up to our
knowledge, no theoretical optimization, structural vibrational and frequency spectra (for example
DFT computations) comparison with the experimental analysis depending on the crystal
structure data were reported before.
As a part of our ongoing work on the synthesis and characterization of such molecules [12-14],
here we have focused on the synthesis and structural investigations of a racemic -3-isobutyl-5-
phenyl-5-(pyridin-4-yl)imidazolidine-2,4-dione. From the theoretical view (geometry
optimization, Hirshfeld surface, MPE, Mulliken population, TD-SCF, HOMO/LUMO and NMR
calculations) and based on the experimental results (XRD, crystal packing, UV and NMR),
efforts have been made to understand the complete description of spectral behavior and the
structural details of the title compound. The existence of different H-bond donor and acceptor
centers in the title compound led to explore mainly three types of hydrogen-bonds viz, N-
H……Npy, C=O…..HCH3 and C=O…..Hph. This fact was experimentally confirmed by XRD
studies and theoretically supported by Hirshfeld surface and MPE calculations.
Experimental

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Bruker APEX-II D8 X-ray diffractometer was used to collect the X-ray diffraction data. Jeol-400
NMR spectrometer was used to run the NMR in DMSO-d6 solvent. PerkinElmer Spectrum 1000
FT-IR, TU-1901 double-beam UV-visible spectrophotometer and TGA-7 PerkinElmer
thermogravimetric analyzer, Elemental analyses were carried out on an Elementar Vario EL
analyzer. All the chemicals and solvents were bought from Merck.
Synthesis of 3-isobutyl-5-phenyl-5-(pyridin-4-yl)imidazolidine-2,4-dione
5-phenyl-5-(pyridin-4-yl)imidazolidine-2,4-dione (0.5 mmol) was dissolved in 60 ml of N,N-
dimethyl formamide, 3.0 mmol of K2CO3 in 10 ml of water and 0.51 mmol of 1-bromo-2-
methylpropane was inserted to the reaction. The reaction mixture was stirred for 10 h at room
temperature and the volume of the solution was reduced to 20 ml under vacuum and then
extracted with 20 ml of ethyl acetate. With the slow evaporation of ethyl acetate from the
solution (over two weeks), white crystals of the title compound were obtained in a very good
yield.
1
(Yield 84%); m.p. > 320 ºC; H NMR (DMSO-d6, 400 MHz) δ: 1.18 (d, 6H, J = 6.5, 2*CH3),
1.95 (m, 1H,CH), 3.92 (d, 2H, J = 7.0, CH2), 7.50-8.30 (m, 9H, Ph and Py), 8.88 (s, 1H, N-H),
13C NMR (DMSO-d6, 100 MHz) δ: 20.5 (2 CH3), 28.1 (CH), 54.1 (CH2), 70.2 (C), 120.0-150.0
(11C, Ph and Py), 159.8 (NC=O), 169.3 (N2C=O); IR (νmaxcm_1) 3520 (N-H), 3300-3200 (C-H,
Ph and Py), 2960-2840 (C-H, alkyl), 1780, 1750 (2C=O). [Calcd. For C18H19N3O2: C, 69.88; N,
13.58; H, 6.19; Found: C, 69.68; N, 13.43; H, 6.08], LC/MS (ESI,): [M+] =309.2m/z measured,
309.7 m/z, calcd].
Computational details
All calculations were made by Gaussian 09 software under DFT/B3LYP/6-311++G(d,p) level of
theory [15]. GaussView 5 software was used to visualize the optimized structures [16]. X-ray

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structure coordinates were taken as starting point for theoretical calculations. CRYSTAL
EXPLORER 3.1 program was used to perform the Hirshfeld surfaces theoretical analysis [17].
Crystallography
A white coloured rectangular shaped single crystal of dimensions 0.28×0.26×0.22 mm of the title
compound was chosen for an X-ray diffraction study. The X-ray intensity data were collected at
a temperature of 296 K on a Bruker Proteum2 CCD diffractometer equipped with an X-ray
generator operating at 45 kV and 10 mA, using CuKα radiation of wavelength 1.54178 Å. Data
were collected for 24 frames per set with different settings of φ(0° and 90°), keeping the scan
width of 0.5°, exposure time of 2 s, the sample to detector distance of 45.10 mm and 2θ value at
46.6°. A complete data set was processed using SAINT PLUS [18]. The structure was solved by
direct methods and refined by full-matrix least squares method on F2 using SHELXS and
SHELXL programs [19]. All the non-hydrogen atoms were revealed in the first difference Fourier
map itself. All the hydrogen atoms were positioned geometrically and refined using a riding
model with Uiso(H) = 1.2 Ueqand 1.5 Ueq(O). After ten cycles of refinement, the final difference
Fourier map showed peaks of no chemical significance and the residuals saturated to 0.0573. The
geometrical calculations were carried out using the program PLATON [20]. The molecular and
packing diagrams were generated using the software MERCURY [21]. The details of the crystal
structure and data refinement are given in Table 1.

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Table 1. Crystal data and structure refinement details.
Parameter
Value
CCDC deposit No.
Empirical formula
Formula weight
1538304
C18H19N3O2
309.36
Temperature
293(2) K
Wavelength
1.54178 Å
Crystal system, space group
Unit cell dimensions
Monoclinic, P21/c
a = 11.5657(19) Å
b = 11.9298(19) Å
c = 12.630(2) Å
β = 111.532(8)º
Volume
1621.1(5) Å3
Z, Calculated density
Absorption coefficient
F(000)
4, 1.268 Mg/m3
0.680 mm-1
656
Crystal size
Theta range for data collection
Limiting indices
Reflections collected / unique
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2σ(I)]
R indices (all data)
Largest diff. peak and hole
0.28 x 0.26 x 0.22 mm
4.11o to 64.44°
-13≤ h ≤ 13, -13 ≤ k ≤ 13, -14 ≤ l ≤ 12
12093/ 2674 [R(int) = 0.0415]
Full-matrix least-squares on F2
2674 / 0 / 210
1.062
R1 = 0.0573, wR2 = 0.1532
R1 = 0.0639, wR2 = 0.1599
0.457 and −0.272 e. Å-3
Results and discussion
Synthesis
The 3-isobutyl-5-phenyl-5-(pyridin-4-yl)imidazolidine-2,4-dione was synthesized in 84% yield,
as shown in Scheme 1. Dehydrobromation of 5-phenyl-5-(pyridin-4-yl)imidazolidine-2,4-dione
and 1-bromo-2-methylpropane in basic medium confirmed the formation of the product in a
good yield and without organic side products. The molecular structure of the product was

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investigated by different spectral techniques such as IR, 1H, 13C-NMR, TG, UV-vis., MS and X-
ray crystallography tools. The structure of the desired compound was optimized using
DFT/B3LYP/6-311G(d,p). The optimized structure parameters were compared with the XRD
experimental data.
O
O
H
N
N
Br
K2CO3
N
N
O
N
O
N
H
H
keto
3ꢀisobutylꢀ5ꢀphenylꢀ5ꢀ(pyridinꢀ4ꢀyl)imidazolidineꢀ2,4ꢀdione
O
N
N
OH
N
enol
2ꢀhydroxyꢀ1ꢀisobutylꢀ4ꢀphenylꢀ4ꢀ(pyridinꢀ4ꢀyl)ꢀ1Hꢀ
imidazolꢀ5(4H)ꢀone
Scheme 1. Synthesis of the title compound.
X-Ray crystal and optimized structure
3-isobutyl-5-phenyl-5-(pyridin-4-yl)imidazolidine-2,4-dione was crystallized from ethyl acetate
solvent. The ORTEP of the molecule is shown in Fig.1a. The crystal data revealed that the
compound crystallized in the monoclinic crystal system with the space group P21/c, with the
crystal lattice parameters: a = 11.5657 (19) Å, b = 11.9298 (19) Å, c = 12.630 (2)
Å and β =
111.532 (8)°. The crystal data is in good agreement with reported structure [22].

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Fig. 1 (a) ORTEP with thermal ellipsoids drawn at 50% probability and (b) DFT- optimized
mononuclear structure of the title compound.
The hydantoin ring in the structure is twisted along the C13-C17 bond with the atom N14
deviating 0.0351(19) Å from the mean plane defined by the atoms C13/N14/C15/N16/C17. The
N-C bond length values of N14-C15 = 1.349(3) Å, N16-C15 = 1.402(3) Å and N16-C17 =
1.357(3) Å are comparable with the values reported earlier [22, 23]. The shortened bond length
values can be attributed to the π conjugation in the hydantoin ring. The structure possesses a
chiral centre at C13 with R configuration. Since the molecule has crystallized in a
centrosymmetric space group, we can surmise that the title compound is a racemate. The dihedral
angle between the hydantoin ring and the phenyl ring is 59.13(15)º whereas the pyridine ring is
subtended by an angle of 80.55(13)º with the hydantoin ring. The dihedral angle between the
pyridine ring and the phenyl ring is 88.51(15)º indicating that they are nearly orthogonal to each
other.

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The bonds in the three rings of the optimized imidazolidene-2,4-dione molecule showed
significant multiple characters with full electron delocalization all over rings, but not methylene
carbon atom which cuts the delocalized expansion revealing colorless compound. In general
imidazolidine-2,4-dione could exist in different tautomeric forms as dione (diketo) or diol (di-
alcohol) or mixed ol-one tautomer [23]. The X-ray crystal structure data helped in clearly
supporting the dione structure tautomer over the other expected tautomer structures, as seen in
Fig. 1a. The DFT-optimized structure of the desired compound is in good agreement with this
fact, as seen from Fig. 1b. The geometrical optimization revealed that diketo structure is the
predominant tautomer over the other expected tautomer forms. A close look at X-ray crystal
structure indicated that theoretical results are in good agreement with the experimental structural
parameters. The bond distances and angles in DFT/B3LYP/6–311+ G(d,p) optimized structure
compared to the crystal data as seen in Table 2 is in good agreement with each other. Plotting of
the X-ray experimental vs. theoretical bond lengths data showed an excellent linear dependency
with the correlation coefficient CC = 0.9785, as seen in Fig. 2a. Plotting of the DFT and XRD
data of selective angles type vs. their values (°) reflected a high degree of compatibility as seen in
Fig. 2b. Angle C17-C13-C5 showed the highest deviation of XRD from the DFT angles values
(2.28%), while angle C13-C16-N16 reflected the lowest deviation with (0.07%).
Table 2. Selected DFT/B3LYP/6–311+ G(d,p) calculated and XRD experimental bond lengths
(Å) and angles (°) of the desired compound.
Angle (°)
Exp.
XRD
B3LYP/6–311+
G(d,p)
Exp.
XRD
B3LYP/6–
311+ G(d,p)
112.37818
110.71289
112.94885
108.15334
100.46592
106.68075
113.25990
107.02678
Bond
N14-C13-C7
N14-C13-C5
C17-C13-C5
C17-C13-C7
C17-C13-N14
N16-C15-N14
C13-N14-C15
C13-C17-N16
111.23
111.86
110.37
109.27
100.63
107.67
112.45
106.95
C1 C2
C1 C6
C2 C3
C3 C4
C4 C5
C5 C6
C5 C13
C7 C8
C7 C12
C7 C13
C8 C9
C9 N10
N10 C11
C11 C12
1.341(5)
1.387(5)
1.349(5)
1.386(5)
1.356(4)
1.351(5)
1.535(3)
1.372(3)
1.374(3)
1.533(3)
1.381(4)
1.314(3)
1.327(4)
1.379(5)
1.39479
1.39115
1.39142
1.39577
1.40128
1.39631
1.53640
1.39349
1.39701
1.53463
1.39551
1.33395
1.33805
1.39110

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C13 N14
C13 C17
N14 C15
C15 N16
C15 O19
N16 C17
N16 C20
C17 O18
C20 C21
C21 C22
C21 C23
CC
1.457(2)
1.543(3)
1.349(2)
1.402(3)
1.214(2)
1.357(2)
1.461(3)
1.211(3)
1.527(4)
1.523(4)
1.513(4)
-
1.46552
1.55908
1.37327
1.40990
1.20939
1.37536
1.46492
1.20830
1.53901
1.53278
1.53470
-
-
0.9130
0.9720

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Fig. 2(a) Graphical correlation of bond lengths (o) experimental vs.DFT/B3LYP/6–311+ G(d,p)
calculated (b) Selective angles types vs. angle value (°) (XRD and DFT).
Several short polar contacts per molecule were detected in the crystal lattice of the desired
compound. The C—H...O hydrogen bond links the molecules to form inversion dimers forming
R2 (14) ring motifs Fig.3a.The molecules are packed in the crystal structure with three classical
2
H-bonds types: N—H……Npy (2.283 Å), as shortest and strongest bond, C=O…..HCH3 (2.602
Å) and C=O…..Hph(2.649 Å), No N—H…..O hydrogen-bond was detected in the crystal lattice

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of the compound. The molecules exhibits layered stacking and are connected by these hydrogen
bonds to form a one dimensional infinite chain along the b axis, see Fig.3c.
Fig.3 (a) C—H…O hydrogen bonds forming R2 (14) ring motifs, and (b) packing of the
2
molecules when viewed down along the b axis forming a one dimensional infinite chain.
Bond energies calculation of both keto and enol form
The 3-isobutyl-5-phenyl-5-(pyridin-4-yl)imidazolidine-2,4-dione as keto form expected to be
more stable than 2-hydroxy-1-isobutyl-4-phenyl-4-(pyridin-4-yl)-1H-imidazol-5(4H)-one enol
isomer, even when their energy difference is not expected to be significant. All the spectral
analysis together with the X-ray crystal structure clearly showed the keto structure is the most
favored in solid state. The bond energy calculations of both isomers also supported this
supported this proposition.

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The bonding differences between the keto and enol structures shown above are:
keto: C=O double bond, N-C single bond, N-H bond
enol: C=N double bond, C-O single bond, O-H bond
If we look up the bond energies for these bonds we find
keto: 745 + 305 + 391 = 1441 kJ/mol
enol: 607 + 358 + 467 = 1432 kJ/mol
This rough calculation tells us that, the keto form will predominate. However the energy
difference between the two forms is only 9 kJ/mol, relatively is very small. In solution it is
possible to find the enol form since the ꢁE of two isomers is very small, while in solid state (as
in this study) with the help of the solved X-ray crystal structure, the keto form structure is
confirmed.
Hirshfeld surfaces analysis (HSA)
The HSA was performed was performed in order to analyze the intermolecular short and long
contacts which can be figured out as visual spots on the surface of the molecule Fig. 4(a). The
red large spots indicate the strong contacts, while the small one is cited as weak interaction [24,
25]. Since the 3-isobutyl-5-phenyl-5-(pyridin-4-yl)imidazolidine-2,4-dione contains acceptor and
receptors functional groups like N-H, N=C and O=C oxygen with mono or bi lone pairs of free
electrons, several types of molecule-to-molecule interactions are usually formed. The strongest
are through H-bonds which can be seen as big spots on the Hirshfeld surfaces of the molecule. In
the Hirshfeld surface structure of the desired molecule, eight remarkable interactions were
detected as sufficient red spots, as shown in Fig. 4a. The interaction succeed in building 3D H-
bonds network through several interaction like N-H……Npy (biggest red spots), C=O…..HCH3
,
and C=O…..Hph, No N—H……O interactions were detected. The interactions obtained by

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Hirshfeld surface analysis are in good agreement with the X-ray crystal structure as seen in the
packing model (Fig.3).
Fig. 4. The Hirshfeld surface of crystal mapped with (a) dnorm, (b) shape index and (c)
curvedness of the title compound
The finger-print plot (FP) of the compound highlights the most important intermolecular contacts
in the molecule. The FP analysis revealed the H----H intermolecular contacts as largest contributor
with 74.8%. The 2D-FP plots over the Hirshfeld surfaces showed the presence of inter-contacts as
the following order: H…H > H…O> H…C > H…N, as depicted in Fig. 5.

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Fig. 5. Finger-print plot of the title compound (Atom inside…Atom outside).

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MEP investigation
Molecular electrostatic potential map is a helpful tool to present not only the electrophilic and
nucleophilic sites on compound surface, but also to recognize the most preferred sites for the H-
bonding interactions. MEP theoretical caculation optimized electronic structure of the title
compound was performed on DFT/B3LYP 6-31+G (d, p), as seen in Fig. 6. The red and blue
colors indicating the H-donor and H-acceptor sites respectively, this controlled the type and
nature of the H-bonding interactions [27]. The potential increased in the following order:
red˂orange˂yellow˂green˂blue, in which it was very interesting to detect the blue color surface
site on the MEP of the desired compound around the N-H function group, which reflected the
degree of the positive region of electrostatic potential of the proton as a powerful H-donor site
with high acidic properties. The MEP graph also indicated that the O of two carbonyls and N of
pyridine with red color is due to the negative region of electrostatic potential as the best H-bond
acceptor sites. The green color predominantly refelected most of the CH hydrogen atoms as
nucleophilic preferred site. The presence of electrophilic and nucleophilic sites play an important
role in the accuracy of the DFT results when compared to the experimental results.

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Fig. 6. The MEP view.
Exponential electronic and theoretical TD-SCF/DFT spectra
Electronic spectrum of the prepared imidazolidine-2,4-dione was measured in DMSO (Fig. 7a).
Experimentally, λmax was found to be 235 nm as strong absorption band due to π to π* electron
transition. No bands were detected in the visible area even though the compound contains three
rings with full electron delocalization, which may be due to the methylene carbon center that cut
the delocalization of electrons between the three rings.
The TD-SCF/DFT was also performed to inspect the electronic absorption of the desired
compound, as shown in Fig 7b. The main calculated λmax value in gas phase was 240 nm. This
experimental band (235 nm) showed very small hypochromic shift (~ 5 nm) due to the solute-

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solvent interactions compared to the gas phase. Negligible solvent effect on λmax values can be
concluded by comparing theoretical with exponential result.
Fig. 7. The electronic spectra of the title compound (a) experimental in DMSO and (b)theoretical
TD-SCF/DFT in gaseous phase.
HOMO-LUMO
Small frontier orbital gap molecules generally are more polarized and reactivated but are less in
kinetic stability [28, 29]. The ionization potential of molecule is concerned directly with HOMO
energy, which pointed out the electron donating capacity. Meanwhile, the electron affinity

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related to LUMO energy degree of electrons acceptation. With the aid of DFT theory, the
electrophilicity, global hardness and chemical potential will facilitate in understanding and
analyzing the structural activities of the title molecule. The energy gap reveals that the electro-
negativity (χ), electrophilicity (ω), the molecule hardness (ƞ) and softness (σ) can be calculated
[30, 31] The molecular orbital energy levels together with their energy gap (0.21292 a.u) are in
agreement with the experimental UV- results. The HOMOꢀLUMO orbital diagram is seen in
Fig. 8.
Fig. 8. HOMOꢀLUMO shape and energy level diagram the molecule.

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Hardness (ƞ) = ELUMO-EHOMO/2 = 5.794/2 = 2.897 eV
Softness (σ) = 1/η=0.345 eV
Electrophilicity (ω) = µ2/2ƞ =2.533eV
Electronegativity (χ) = -EHOMO+ -ELUMO /2 = 7.662/2 = 3.831 eV
Chemical potential (µ) = -X= -3.831 eV
Electrophilicity (ω) = µ2/2ƞ =4.676/5.794 = 2.533 eV.
The hardness value (2.897 eV) of the molecule contemplated the polarizability with sufficient
amount which makes it a soft compound with faster electron transfer. The value of chemical
potential (−3.831 eV) revealed the stability and non-spontaneous decomposition of the molecule,
the electronic attraction power was indicated by electrophilicity and electro-negativity values.
Mulliken atomic charge population analysis
Mulliken charge of atoms play an essential role as quantum theoretical calculation in molecular
charge distribution. The atomic charge distribution of acceptor and donor atoms in molecules
directly affect many parameters like: polarizability, dipole moment, refractivity and electronic
structural parameters [32]. B3LYP/6-31G(d,p) was performed to calculate the Mulliken
population charge analysis of the compound as seen in Table 3 and Fig. 9. The analysis revealed
the presence of nucleophilic (-ve, donor) and electrophilic (+ve, acceptor) atomic charge in the
molecule. The electrophilic are localized at all the hydrogen atoms in the molecule with ~+0.15-
0.35e values, the largest positive charge H atom was found on H24 (H-N) with 0.344025e, which
consisted with the acidity of such proton and MPE analysis result. The electrons delocalized on
the affected three rings influences nucleophilicity of most of the carbon atoms in the three rings.
The C22 atom revealed the largest positive charge with 0.944878e; this electrophilicity indicated
that this carbon was not engaged on the electrons delocalization in the phenyl, pyridyl and
imidazolidine rings. Furthermore, C27 though it is a carbonyl carbon atom (expected to be

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electrophilic) showed the highest nucleophilicity (-0.728409e) due to the effective electron
delocalization in the imidazolidine ring. The analysis revealed the high electro-negativity of O28
and O29 atoms with less than expected nucleophilicity amounts to -0.177629e and -0.311208e
respectively. The same thing with N atoms, N17-0.063527e, N23-0.298969e, while N26 is with
+0.232332e.
Fig. 9. Mulliken charge distribution of each atom in the title compound.

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Table 3. Mulliken charges of atoms in title compound.
No.
1
Atom
C
Charge
No.
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
Atom
C
Charge
-0.339734
0.181435
-0.308587
0.159624
-0.419696
0.194791
-0.398566
0.213178
0.444610
-0.317299
0.176672
-0.062812
0.297923
0.226672
-0.621884
0.190262
-0.063527
-0.674455
0.187329
0.370901
0.225230
0.944878
-0.298969
0.344025
0.116135
0.232332
-0.728409
-0.177629
-0.311208
-0.436191
0.206178
0.201894
0.328845
0.199174
-0.662343
0.147819
0.137896
0.138674
-0.486085
0.129262
0.153064
0.158591
2
H
C
N
H
C
3
4
H
C
5
N
C
6
H
C
7
O
O
C
8
H
C
9
10
11
12
13
14
15
16
17
18
19
20
21
C
H
H
C
H
C
C
H
C
H
C
H
H
H
C
H
N
C
H
C
H
H
H
H

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FT-IR investigations
The IR spectra serve to detect the functional groups of the prepared compound. The IR
spectrum revealed in particular the five main characteristic vibrations: (3520 cm-1, N-H), (3300-
3200 cm-1, CPh-H), (2990-2840 cm-1, Calkyl-H) and (1780-1750 cm-1, 2C=O), the other functional
groups were cited to their positions, as seen in Fig.10.
Fig. 10. FT-IR spectrum of the title compound.
Theoretical 1H NMR compared to experimental result
ACD-LAB and NMR-DB [33] 1H NMR theoretical calculations in gaseous state were compared
to the experimental 1H NMR result which was performed in DMSO solvent. The calculated and
1
experimental spectra are given in Fig 11. The theoretical HNMR (chemical shifts) using both
programs showed an excellent correlation with the experimental results. NMR-DB versus
1
experimental HNMR revealed correlation coefficient R2= 0.9945, while ACD-LAB versus
experimental 1HNMR gave significant R2= 0.9979, as seen in Fig. 11.

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Fig. 11.1H NMR spectra of compound: a) Experimentally in DMSO-d6, b) Theoretically using
NMR-DB compared to experimental c) Theoretically using ACD-lab compared to experimental.

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TG/DTG investigation
Thermal TG/DTG analysis was performed to evaluate the thermal stability of the title
compound in an open atmosphere condition over 0 to 500 °C temperature range and 10 °C/min
heat rate, as shown in Fig. 12. The organic formula of the compound [C18H19N3O2] revealed a
good thermal stability range between 0-180°C. The thermal decomposition started from 200°C
and ended at 300°C. The compound decomposed completely to light gases such as: NO2, CO2
and H2O, with 100% mass loss. Therefore, the compound proceeded with no-intermediate one-
step thermal decomposition.
Fig. 12. TG of the title compound.
Conclusions
The 3-isobutyl-5-phenyl-5-(pyridin-4-yl)imidazolidine-2,4-dione has been synthesized in a very
good yield and characterized physico-chemically. The structure was solved by X-ray diffraction
method to an accuracy of R = 0.0573. The optimized structure, TD-SCF, HOMU-LUMO, MPE,

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Mullikan charge were calculated by DFT/B3LYP/6-31G(d,p) and then compared with the
experimental results. Hirshfeld surface analysis was performed to establish the intermolecular
contacts, suitable H-bonding interactions N-H……Npy, C=O…..HCH3 and C=O…..Hph sites were
detected by Hirshfeld surface analysis and MEP map theoretical calculations and then compared
with the X-ray packing diagrams. The calculated NMR results were compatible with the
experimental one. The desired compound displayed a good thermal stability with one step
thermal decomposition mechanism.
Acknowledgements
The authors are thankful to the Institution of Excellence, Vijnana Bhavana, University of
Mysore, Manasagangotri, Mysore, for providing the single-crystal X-ray diffraction data.
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