Synthesis, crystal structure, Hirshfeld surface analysis and DFT calculations of 2, 2, 2-tribromo-1-(3,5-dibromo-2-hydroxyphenyl)ethanone

Article abstract of DOI:10.1016/j.molstruc.2021.131313

A novel derivative 2, 2, 2-tribromo-1- (3,5-dibromo-2-hydroxyphenyl) ethanone was synthesis by “3-acetyl-4-hydroxycoumarin” and dibromide. The structural properties of the synthesized compound have been exploited with the aid of single-crystal X-ray crystallographic studies and infrared spectrometry. The compound crystallizes in the monoclinic system with space group P2₁/c. A comparative study between the novel brominated compound synthesized and the brominated coumarin derivative is presented. The optimized DFT geometries (B3PW91/6–311 G (2df, p)) and the spectral simulations of two derivatives compared agree well with the experimental data. Hirshfeld's analysis revealed the importance of Br ··· Br (40%) and Br ··· H/H ··· Br (19%) of the total surface contacts in the molecular stack. The contacts O···H/H···O have a significant contribution for the brominated coumarin (C2) of 26.1% of SH compared to the brominated cycle (C1) 9.7%.

Full text of DOI:10.1016/j.molstruc.2021.131313

Journal of Molecular Structure 1248 (2022) 131313
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Synthesis, crystal structure, Hirshfeld surface analysis and DFT
calculations of 2, 2, 2-tribromo-1-(3,5-dibromo-2-
hydroxyphenyl)ethanone
Ameni Brahmiaa,b,∗, Linda Bejaouib, Jan Rolicekc, RachedBen Hassenb,
Goncagül Serdarog˘lud, Savas¸ Kayae
a Chemistry Department, College of Science, King Khalid University, Abha 61413, Saudi Arabia
b Laboratoire des Materiaux et de l’Environnement pour le Développement Durable, LR18ES10, University of Tunis El Manar, Tunis 2092, Tunisia
c Institute of Physics AS CR, v.v.i., Na Slovance 2, Prague 8 182 21, Czech Republic
d Department of Mathematics and Science Education, Sivas Cumhuriyet University, Sivas 58140, Turkey
e Department of Pharmacy, Health Services Vocational School, Sivas Cumhuriyet University, Sivas 58140, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel derivative 2, 2, 2-tribromo-1- (3,5-dibromo-2-hydroxyphenyl) ethanone was synthesis by “3-
acetyl-4-hydroxycoumarin” and dibromide. The structural properties of the synthesized compound have
been exploited with the aid of single-crystal X-ray crystallographic studies and infrared spectrometry. The
compound crystallizes in the monoclinic system with space group P21/c. A comparative study between
the novel brominated compound synthesized and the brominated coumarin derivative is presented. The
optimized DFT geometries (B3PW91/6–311 G (2df, p)) and the spectral simulations of two derivatives
compared agree well with the experimental data. Hirshfeld’s analysis revealed the importance of Br ···
Br (40%) and Br ··· H/H ··· Br (19%) of the total surface contacts in the molecular stack. The contacts
O···H/H···O have a significant contribution for the brominated coumarin (C2) of 26.1% of SH compared to
the brominated cycle (C1) 9.7%.
Received 10 March 2021
Revised 11 August 2021
Accepted 14 August 2021
Available online 16 August 2021
Keywords:
Brominated compound
Coumarin derivatives
X-ray diffraction
DFT calculation
Hirshfeld analysis
© 2021 Published by Elsevier B.V.
1. Introduction
as photosensitizers and chemotherapeutic agents to fight skin
diseases [7]. Rao and Kumar also claimed that the bromination
Brominated coumarins present a wide range of biological activ-
ities and important applications in pharmaceuticals, due to their
occurrence in nature [1]. Coumarin derivatives are sensitive to
electrophilic substitution [2]; their reaction with Bromine can give
rise to several compounds used as intermediate products sensi-
tive to interesting substitutions in a wide range of organic synthe-
ses [3]. The bromination of these compounds increases their an-
ticonvulsant activity [4], which convert them pharmacological im-
portance. They also have interesting biological properties as pow-
erful antioxidants, as well as acceptable antimicrobial and anti-
tuberculosis activities [5]. Coumarins containing halogens have in-
secticidal and fungicidal properties [6].
of coumarin increases its reactivity and promotes chemoselective
reactions [8]. Bromo-coumarins are used as starting reagent in
the preparation of 3-arylcoumarins [2–10], 1,3,4-oxadiazole deriva-
tives, and benzofuran-2-carboxylic acids by a Perkin rearrange-
ment reaction [11]. Therefore, the synthesis of brominated 3-
aminocoumarins becomes very interesting among organicists. Re-
cent research suggests that Bromo-coumarins also have power-
ful optical and biological properties and they could increase the
reactivity of coumarins and favor chemo selective reactions. In
this context, our research group recently reported the synthe-
sis of a new brominated derivative prepared from 3-acetyl-4-
hydroxycoumarin. The molecular structure was carried out by X-
ray crystallography, Hirschfeld surfaces analysis, and DFTB3LYP
method with the basis set 6-311++G (d,p). Additionally, the UV-
Vis spectroscopic behavior of this derivative in different solvents
was investigated. The present study concerns the structural com-
parison and the biological activity of new brominated compound
and brominated coumarin already studied [12].
Brominated coumarins were used as synthetic precursors of
furocoumarins and furocoumarins dihydro, which are widely used
∗
Corresponding author at: Chemistry Department, College of Science, King Khalid
University, Abha 61413, Saudi Arabia.
E-mail address: ameni.brahmia@yahoo.fr (A. Brahmia).
https://doi.org/10.1016/j.molstruc.2021.131313
0022-2860/© 2021 Published by Elsevier B.V.

A. Brahmia, L. Bejaoui, J. Rolicek et al.
2. Experimental
Journal of Molecular Structure 1248 (2022) 131313
scriptors are presented via the following equations [30].
ꢁ
ꢂ
ꢃ
ꢄ
∂E
I + A
2.1. Infrared and UV-visible spectroscopies
μ = −χ =
= −
∂N
2
ν(r)
ꢁ
ꢂ
The starting compound ‘3-acetyl-4-hydroxycoumarin’ was pre-
pared as previously described [13]. The IR spectrum was recorded
on a Bruker FT-IR spectrophotometer Tensor 27 by KBr pellet tech-
nique in the range 4000–400 cm–1. The electronic absorption spec-
tra were recorded on double beam UVD-3500 UV-Vis spectrometer
in methanol and ethyl acetate in the region 200–900 nm.
1
∂2E
2 ∂N2
I − A
η =
=
2
ν(r)
σ = 1/η
As can be seen from the equations given above, to calculate
the quantum chemical descriptors given, we need to ionization en-
ergy and electron affinity parameters. It is important to note the
ionization energy and electron affinity values of molecules can be
predicted with the help of frontier orbital energies in the light of
Koopmans Theorem [31]. The theorem states that negative values
of HOMO and LUMO orbital energies of any molecule correspond
to ionization energy and electron affinity values of the aforemen-
tioned molecule
2.2. Hirshfeld surface analysis
The Hirshfeld surface becomes a valuable tool for analyzing the
intermolecular interactions of an entire molecule. It is defined by
the isosurface 0.5 of the weight function w(r) (Eq. 1). The sum of
the electron densities of spherical atoms of the molecule (the pro-
molecule) divided by the same sum for the crystal (the procrys-
tal) inside the surface of Hirshfeld, the electron density of the pro-
molecule dominates the procrystal [13].
I = −EHOMO
A = −ELU MO
By defining a function of molecular weight w(r):
ꢀ
ρ promoécule(r)
ρ procristal(r)
ρA(r) A ∈ molécule
[
]
Parr, Szentpaly and Liu [32] modeled the electrophilicity in-
dex based on electronegativity (or chemical potential) and chem-
ical hardness of any chemical species via the following equation.
ꢀ
ω(r) =
=
ρA(r) A ∈ cristal
[
]
ρA (r): the average electron density of an atomic nucleus A cen-
tered on this nucleus.
ω = χ2/2η
For a point on the surface, the distances to the nearest atoms
outside, de, and inside, di, are easily defined and are used as prop-
erties, can define the identity of these atoms and to explore inter-
molecular contacts in a crystal.
Then, Chattaraj [33] proposed that nucleophilicity can be given
as the multiplicative inverse of electrophilicity index as ε = 1/ω.
Polarizability [34] that is one of the useful reactivity descriptors
is calculated depending on diagonal components of polarizability
tensor.
In addition, a normalized contact distance, dnorm (Eq. 2), is de-
fined where rvdW is the van der Waals radius (vdW) of the appro-
priate internal or external atom at the surface.
α = 1/3 αxx + αyy + αzz
ꢀ ꢁ
[
]
vdW
vdW
di − ri
de − re
2.4. General procedure for synthesis of the brominated derivatives
(C1) and (C2)
dnorm
=
+
vdW
vdW
ri
re
The intermolecular interactions of the present simple are quan-
tified using Hirshfeld surface analysis. The program CrystalExplorer
3.1 [14] established the Hirshfeld surface analyzes by introducing
into this software a file of the studied structure in CIF format.
An excess of dibroma (10 equivalent) dissolved in acetic acid
was added dropwise to
a solution of 3-acetyl-4-hydroxy-2H-
chromene-2-one in acetic acid. During the reaction, the dropwise
addition was carried out after each disappearance of the brown
coloration of the dibroma (Br2). The reaction mixture was kept stir-
ring at 373 K until the brown color persisted. The solution obtained
was crystallized at room temperature to obtain a crystalline pow-
der containing two types of crystals, the first of the transparent
colorless crystals with a melting temperature equal to 393 K and
2.3. Quantum chemical calculations
The B3LYP [15,16] and M06-2X [17] calculations were per-
formed by G09W [18] package, in the gas, DMSO and Water
phases, at 6-311++G(d,p) basis set. The gas-phase optimized and
verified structure of the compound, which had no imaginary fre-
quency, was been used for the solvent media calculations. For
the solvent environment calculations, the PCM (polarized con-
tinuum model) was used [19,20]. The vibrational mode assign-
ment of the compound has been performed by PED (potential en-
ergy distribution) analysis by VEDA [21], and the O-H and aro-
matic C-H frequencies have been scaled down [22] by the factor
0.960 for B3LYP/6-311++G(d,p) level. The NBO (natural bond or-
bital) [23,24] investigation has conducted to evaluate the structure-
intramolecular interactions relationship. The FMO (frontier molecu-
lar orbital) analysis [25–28] has been used to evaluate the chemical
reactive behavior of the compound by using the DFT-based reactiv-
ity descriptors.
Conceptual Density Functional Theory [29] based equations are
widely used in the calculation of quantum chemical descriptors
like hardness, softness, electronegativity and chemical potential.
The relation with total electronic energy, number of electrons, ion-
ization energy and electron affinity of the mentioned reactivity de-
Fig. 1. The infrared absorption spectra of C1 and C2.
2

A. Brahmia, L. Bejaoui, J. Rolicek et al.
Journal of Molecular Structure 1248 (2022) 131313
Fig. 2. The UV-Visible spectra of C1:(a) and C2:(b) in different solvents.
68% yield (assigned to C1 in the present work), and, the second
yellow, with a melting temperature equal to 388K and 32% yield
(assigned to C2 [12] in the present work).
O) of the hydroxyl group. On the other hand, the ketonic group
νC=O and the hydroxyl group (νC-O) modes for C1 molecule have
been assigned as a pure mode in 1689 and 1300 cm−1. Besides,
the ketonic group νC=O mode has contributed (11%) to the aro-
matic νCC (36%) and ipb HCC (in-plane-bending, 33%) modes in
1454 cm−1. Also, the assigned modes in 1393 and 1320 cm−1 for
C1 molecule have also included the ketonic group νC=O mode
contribution to the ipb HCC and ipb HOC bending modes. From
Table S1, the νC=O vibrational modes with very strong IR inten-
sity for the C2 molecule (Fig. 1), includes two ketonic group, have
been assigned as a pure mode in 1786 (85%) and 1663 cm−1 (64%).
The bands observed at 1413 and 663 cm−1 can be attributed to
the valence vibration of the aromatic C-C bond and the elonga-
tion vibration of the Br-C (νBrC) bond. In this context, the assigned
mode for C1 in 693 cm−1 has contained the νBr-C mode contribu-
tion (60%) as mixed with the bending modes of δ(CCC Ring+ CCO+
CCBr (10%). In addition, the assigned νBr-C mode in 571 cm−1 has
included the torsion (χ CCCC, 10%) and the bending (δBrCBr, 16%)
contributions. On the other hand, νBrC mode for C2 has been as-
signed in 552 cm−1 purely and in 761 and 206 cm−1 as contam-
inated with the bending modes. All vibrational mode assignment
3. Results and discussion
3.1. Infrared spectroscopy
The infrared spectrum of the pentabromo-derivative (C1) “2,2,2-
tribromo-1- (3,5-dibromo-2-hydroxyphenyl) ethanone” (Fig. 1)
shows a band around 3170 cm−1 which can be attributed to the
valence vibration of the OH bond (νOH) of the hydroxyl group.
Also, νOH stretching mode has been assigned as a pure mode
(99%) at 3263 cm−1 with very strong intensity (Table S1: Supple-
mentary material). The bands corresponding to the valence vibra-
tions of the aromatic C-H bonds that appeared around 3099 and
3043 cm−1 have been predicted in 3130 (99% PED) and 3087cm−1
(100% PED). and that of C-C stretching vibration revealed around
1015 cm−1. The bands of elongation observed around 1713, 1651
and 1264 cm−1 can be attributed, respectively to the vibrations of
the C=O ketone (νC=O), C=C aromatic (νCC) and C-O bonds (νC-
Table 1
The experimental and theoretical UV-vis absorption characteristics of compound (C8H3O2Br5).
Exp.(λnm)
Transitions
MO%
ꢀE (eV)
λ (nm)
f
C1
Ethyl acetate
(ε=6.02)
334
313
H→L
(99%)
(15%)
(81%)
(84%)
(14%)
3.1012
3.9669
399.80
312.55
0.0771
0.1079
H-2 →L
H-1 →L
H-2 →L
H-1 →L
—
4.1113
301.57
0.0231
Methanol
348
310
H→L
(96%)
(42%)
(53%)
(57%)
(38%)
3.1996
4.0302
387.50
307.64
0.0901
0.0826
(ε=32.63)
H-2 →L
H-1 →L
H-2 →L
H-1 →L
—
4.1439
299.20
0.0698
C2
Ethyl acetate
(ε=6.02)
335
331
H→L
(97%)
(54%)
(11%)
(24%)
(42%)
(22%)
(24%)
3.5484
3.9123
349.41
316.91
0.1163
0.2245
H-1 →L
H-3 →L
H-4 →L
H-1 →L
H-3 →L
H-4 →L
311
3.9834
311.25
0.1938
Methanol
335
331
H→L
(94%)
(11%)
(25%)
(44%)
(75%)
(11%)
3.6212
3.9492
342.38
313.95
0.1182
0.0588
(ε=32.63)
H-1 →L
H-3 →L
H-4 →L
H-1 →L
H-3 →L
311
4.0794
303.93
0.4577
3

A. Brahmia, L. Bejaoui, J. Rolicek et al.
Journal of Molecular Structure 1248 (2022) 131313
Fig. 3. HOMO and LUMO amplitudes contributed to the electronic transitions (isoval:0.02) of C1 and C2 molecules at B3LYP/6-1+G(d,p) level in the methanol.
details of the compound can be found in Table S1. These attri-
butions show all the bonds of the expected molecular structure,
the subsequent analysis by X-ray diffraction can specify the exact
structure.
interest chemical species have been calculated greater 30-40 nm
approximately than the observed data [38–40].
Accordingly, the UV-Vis spectrum of compound C1 revealed two
peaks in 348 and 310 nm in methanol and in 334 and 313 nm
in ethyl acetate. Furthermore, the first peak of C1 calculated in
399.80 nm in ethyl acetate and 387.50 nm in methanol sourced
from the π→ π∗ transition was related to mostly H→ L transi-
tion (99%). From Table 1, the second peak of compound C1 was
calculated at 312.55 nm and overlap with the electronic transition
calculated at 301.57 nm, which both transitions were due to the
H-2 →L and H-1 →L and characterized by the n→π∗ interaction.
Besides, the first excitation for C2 came from H→ L were calcu-
lated at 349.41 in ethyl acetate nm and 342.38 nm in methanol
and appeared in 335 nm of the spectrum. From Table 1, the second
peak of C2 observed in 331 nm was predicted in ethyl acetate in
316.91 nm (f= 0.2245) that was due to the mainly H-1 →L (54%),
as well as the transitions of H-3 →L (11%) and H-4 →L (24%).
Also, the third summit on the spectrum of C2 was 311 nm in both
the ethyl acetate and methanol and calculated as 311.25 nm (f=
0.1938) in ethyl acetate and in 303.93 nm in methanol, caused by
3.2. Ultraviolet-visible characterization
The ultraviolet-visible spectroscopy of C1 and C2 derivatives
was studied through dilute solutions of methanol and ethyl ac-
etate, with the concentration 1.3 × 10−5 M. The choice of solvents
was based on the difference in polarity and the ability to form
hydrogen bonds. The recorded spectra and characterization of the
electronic transitions of both C1 and C2 were given in Fig. 2 and
Table 1, respectively.
Besides, TD-DFT/B3LYP/6-311G(d,p) [35–37] calculations were
conducted to characterize the electronic transition in the UV-Vis
spectrum of the compound (C8H3O2Br5). Table 1 disclosed the
electronic transitions, molecular orbital contributions to the rele-
vant transition, the energy gap between the singlet states, and os-
cillator strength. As reported in the past, the theoretical peaks of
4

A. Brahmia, L. Bejaoui, J. Rolicek et al.
Journal of Molecular Structure 1248 (2022) 131313
Table 2
The second order perturbation theory analysis of fock matrix in NBO basis of C1 and C2 molecules at B3LYP/6311++G(d,p) level in the gas phase.
Donor(i)
EDi/e
Acceptor (j)
EDj/e
E(2)/kcal/ mol
E(j)-E(i)/ a.u
F(i.j)/ a.u
C1
π C1-C2 (2)
π C5-C6 (2)
σ C12-Br15 (1)
σ C12-Br16 (1)
LP (3) Br17
LP (3) Br18
1.71764
1.71509
1.97755
1.97756
1.94180
1.93000
π∗ C5-C6
π∗ C1-C2
π∗ C11-O13
π∗ C11-O13
π∗ C1-C2
π∗ C5-C6
0.33446
0.33733
0.21723
0.21723
0.33733
0.33446
22.80
14.30
2.52
0.29
0.30
0.63
0.63
0.30
0.29
0.073
0.059
0.038
0.038
0.052
0.052
2.52
9.66
10.25
C2
π C1-C2 (2)
1.67625
1.61117
π∗ C3-C4
0.43328
0.26965
0.29216
0.26965
0.36230
0.29216
0.43328
0.43328
0.29596
0.25480
0.29596
0.25480
0.25480
0.43328
0.29596
0.25480
24.28
15.91
14.46
18.96
10.64
21.68
17.11
8.38
0.27
0.29
0.30
0.31
0.63
0.28
0.27
0.29
0.72
0.45
1.05
0.79
0.76
0.35
0.78
0.45
0.075
0.062
0.060
0.070
0.073
0.070
0.063
0.045
0.084
0.087
0.058
0.047
0.032
0.098
0.098
0.023
π∗ C5-C6
π C3-C4 (2)
π∗ C1-C2
π∗ C5-C6
π∗ C9-C12
π∗ C1-C2
π C5-C6 (2)
1.68763
1.67127
π∗ C3-C4
π C9-C12 (2)
π∗ C3-C4
π∗ C13-O17
π∗ C18-O21
π∗ C13-O17
π∗ C18-O21
π∗ C18-O21
π∗ C3-C4
12.23
20.28
3.51
σ C19-Br22 (1)
1.98501
3.11
σ C19-Br23 (1)
1.96759
1.74807
1.56
LP (2) O16
31.34
15.24
1.31
π∗ C13-O17
π∗ C18-O21
LP (3) Br23
1.94473
(Fij)2
(ε j−εi)
∗
(2)
E
= ꢀEij = qi
shows the lowering of stabilization energy, where qi is the donor orbital occupancy, εi, and εj are donor and acceptor orbital energies (diagonal
elements), and Fij is the off-diagonal NBO Fock matrix element.
the n→π∗ excitations. The results of the electronic spectra of both
compounds disclosed that there were a significant hypsochromic
effect for C1 and hyperchromic effect for C2.
gap 3.6212 eV, and it is clear that this transition could be also
the π→ π∗ transition because both H and LUMO were largely dis-
tributed over the π-conjugate system. Moreover, the second peak
for C2 observed at 331 nm was associated mainly with the states
H-4→ L (44%), H-3→ L (25%), and H-1→ L (11%). From Fig. 3, the
H-3 and H-4 amplitudes were greatly spread out on the -Br atoms,
which could be a sign of the n→ π∗ interaction, whereas H-1→L
transition characterized as π→ π∗ transition also contributed to
the second peak.
In addition, the FMOs density for s1←s0 electronic transitions
that occurred in both compounds were given in Fig. 3. For com-
pound C1, the first excitation has taken place from the Br and -
OH substituted phenyl ring, towards the aliphatic bonded two Br
atoms and the whole aromatic ring, and this excitation was mainly
associated with the π→ π∗ transition. Besides, the second peak
was due to the electronic excitations H-1→ L and H-2→ L, namely,
the electron density on the excited state for H-1 was distributed
on the -π and non-bonding orbitals whereas it for H-2 was mainly
on the non-bonding orbital and partially aromatic ring. Here, H-1
and H-2 states could be associated with the π→ π∗ and n→ π∗
interactions, respectively. For compound C2, the first electronic ex-
citation was calculated for the H→ L transition with the energy
Furthermore, the important electron delocalization between the
donor and acceptor molecular orbitals, which each contributes to
the stabilization energy lowering, has been predicted by using the
NBO analysis. NBO analysis has been successfully applied to ex-
plain the properties of the relevant chemical species such as sta-
bility, polarization, and electronic transitions, etc [41–43]. Thus, the
results obtained from the NBO analysis summarized in Table 2 the
important interactions that occurred in the compounds of rele-
vance. Based on the results of the C1 molecule, the highest con-
tribution to the lowering of the stabilization energy has been cal-
culated for the electron delocalization from the π C1-C2 bond-
ing orbital to π∗ C5-C6 anti-bonding orbital, with the energy of
22.80 kcal/mol. Also, the perturbative energy for π C5-C6→ π∗ C1-
C2 resonance interaction of the C1 molecule has been calculated
as 14.30 kcal/mol (EDi/e=1.71509 e). On the other hand, for the
C2 molecule, LP (2) O16→ π∗ C3-C4 as the resonance interaction
has the highest contribution to the stabilization of the molecule
with E(2)=31.34 kcal/mol with the remarkable orbital occupancy
(EDi/e=1.74807 e). From Table 2, the hyperconjugative interactions
(σ→ π∗) have also contributed to the stabilization energy; the sta-
Table 3
The crystallographic data, the conditions of intensity collection and the refinement
of C8H3O2Br5 (C1).
Chemical formula
C8H3O2Br5
Molecular weight
Crystal system
Space group
530.6
Monoclinic
P21/c
Temperature (K)
293
˚
a, b, c (A)
10.1770 (6), 10.2843 (6), 12.1938 (9)
β (°)
107.143(6)°
3
˚
V (A )
1219.5(2)
Z
4
Radiation type
Density (mm−1
Diffractometer
Cu Kα
)
2,885
Oxford diffraction Gemini diffractometer with
Table 4
four circles, an Atlas CCD detector
˚
Hydrogen-bonds geometry of structure C8H3O2Br5 (A, °).
Scan range [°]
F(000)
R[F2 > 2s(F2)], wR(F2), S
θmax = 66.9°, θmin = 5.4°
968
D—H···A
D—H
H···A
D···A
D—H···A
0.029, 0.040, 1.11
O1—H2o1···O2
O1—H2o1···O2i
0.82
0.82
1.97
2.32
2.578 (5)
3.024 (6)
130.46
144.91
No. of reflections
2071
No. of parameters
H-atom treatment
136
H-atom parameters constrained
Symmetry code: (i) -x+1, -y+1, -z+1.
5

A. Brahmia, L. Bejaoui, J. Rolicek et al.
Journal of Molecular Structure 1248 (2022) 131313
Fig. 4. The molecular structure of C8H3O2Br5 (C1), the displacement ellipsoids are established with a probability of 50%.
bilization energy for the electron delocalization from each of both
the σ C12-Br15 and σ C12-Br16 bonding orbitals to π∗ C11-O13
antibonding orbital for the C1 molecule have been calculated in
2.52 kcal/mol. Also, the energies of LP (3) Br17→ π∗ C1-C2 and LP
(3) Br18→ π∗ C5-C6 resonance interactions (C1) have been pre-
dicted in 9.66 and 10.25 kcal/mol, remarkable in terms of con-
tributing to the stabilization energy. However, for the C2 molecule,
the stabilization energy for LP (3) Br23→ π∗ C18-O21 interaction
is found to be in 1.31 kcal/mol, which is smaller than that of the
counterpart interaction calculated for the C1 molecule.
Table 5
The selected optimized parameters of C1 and C2 molecules at B3LYP/6-311++G(d,p) level in the gas phase.
˚
Bond Length
(A)
Bond angle
(°)
Dihedral angle
(°)
C1
C1-Br17
C5-Br18
C12-Br14
C12-Br15
C4-O9
1.91
1.90
1.96
1.98
1.33
1.22
0.98
1.08
1.38
1.43
1.48
1.57
C1-C2-C3
120.7
118.6
123.7
107.9
119.1
119.0
117.3
121.2
116.1
110.3
109.4
108.1
C1-C2-C3-C4
0.0
C3-C4-C5
C1-C2-C3-C11
-180.0
180.0
0.0
C3-C4-O9
C2-C3-C4-O9
C4-O9-H10
C4-C5-Br18
C6-C1-Br17
C4-C3-C11
O9-C4-C5-Br18
C2-C3-C11-O13
C2-C3-C11-C12
C4-C3-C11-O13
C3-C11-C12-Br14
C3-C11-C12-Br15
C3-C11-C12-Br16
O13-C11-C12-Br14
O13-C11-C12-Br15
-180.0
0.0
C11-O13
O9-H10
C2-H7
0.0
C3-C11-O13
C12-C11-O13
C11-C12-Br14
C11-C12-Br15
Br14-C12-Br15
180.0
-61.3
61.2
-0.0
C1-C2
C3-C4
C3-C11
C11-C12
118.7
C2
C19-Br22
C19-Br23
C9-O14
C18-O21
O14-H15
C2-H8
1.95
1.98
1.31
1.24
1.00
1.08
1.39
1.36
1.39
1.21
1.47
1.53
C2-C3-C4
121.0
123.5
116.9
127.3
115.8
116.7
117.6
120.7
120.5
118.8
111.7
112.7
C1-C2-C3-C4
-0.0
C3-O16-C13
O16-C13-C12
O12-C13-O17
O16-C13-O17
C4-C9-O14
C2-C3-C4-C9
-179.7
-179.7
178.8
-0.6
C3-C4-C9-O14
C13-C12-C9-O14
O14-C9-C12-C18
C9-C12-C18-O21
C3-O16-C13-O17
O16-C13-C12-C18
O17-C13-C12-C18
C13-C12-C18-O21
O21-C18-C19-Br22
O21-C18-C19-Br23
2.8
C1-C2
C9-C12-C18
C12-C18-C19
C12-C18-O21
C19-C18-O21
C18-C19-Br22
Br22-C19-Br23
179.3
-179.2
1.2
C3-O16
C13-O16
C13-O17
C12-C18
C18-C19
-176.6
37.5
-86.0
6

A. Brahmia, L. Bejaoui, J. Rolicek et al.
Journal of Molecular Structure 1248 (2022) 131313
Table 6
The quantum chemical reactivity identifiers, total electronic and free energies of C1 and C2 molecules (CH+ shows the protonated
forms in the gas phase) at B3LYP/6-311++G(d,p) level.
C1
Gas
DMSO
WATER
CH+ (Gas)
HOMO (-I)
LUMO (-A)
ꢀE (L-H)
μ=-(I+A)/2
η=(I-A)/2
ω=μ∗μ/2η
ꢀNmax=-μ/η
α (au)
-0.25470
-0.25190
-0.25187
-0.38662
-0.12180
-0.11694
-0.11688
-0.29890
3.61640
3.67245
3.67327
2.38698
-5.12255
-5.01833
-5.01710
-9.32698
1.80820
1.83623
1.83663
1.19349
7.25598
6.85744
6.85257
36.44454
7.81487
2.83296
2.73296
2.73168
209.2316520
1.4024280
-13327.8349850
-13327.8837050
290.838119
2.181652
-13327.841827
-13327.890549
292.413946
2.196982
-13327.841940
-13327.890647
214.605065
3.463392
-13328.138048
-13328.186995
D (debye)
ꢀE (au)
ꢀG (au)
C2
HOMO (-I)
LUMO (-A)
ꢀE (L-H)
μ=-(I+A)/2
η=(I-A)/2
ω=μ∗μ/2η
ꢀNmax=-μ/η
α (au)
-0.27421
-0.26838
-0.11564
4.15627
-0.26829
-0.11560
4.15491
-0.40442
-0.11872
-0.28759
4.23110
3.17911
-5.34609
-5.22486
2.07813
-5.22309
2.07745
-9.41528
2.11555
1.58955
6.75490
6.56819
6.56589
27.88440
5.92322
2.52704
2.51421
2.51418
193.4973800
5.9767500
-5872.0358690
-5872.0814130
266.789155
8.335716
-5872.047883
-5872.093123
268.141813
8.371225
-5872.048080
-5872.093303
200.686587
7.681388
-5872.353580
-5872.398755
D (debye)
ꢀE (au)
ꢀG (au)
3.3. Single crystal XRD study
The crystal of this derivative was characterized by an Oxford
Diffraction Gemini diffractometer with four circles using Cu Kα ra-
diation with a collimating mirror from a sealed X-ray tube and an
Atlas CCD detector. The structure was solved by direct methods
using Superflip software [44], and the refinement was carried out
with JANA 2006 software [45]. The hydrogen atoms bound to car-
˚
bons were geometrically fixed (C-H = 0.93 or 0.98 A) and refined,
with Uiso (H) fixed at 1.2 Ueq from the central atom. The struc-
ture was registered in the CCDC database under deposition number
2068709.
The experimental details including structure refinement and
data collection details for C8H3O2Br5 (C1) were summarized in
Table 3. The crystal structures presented in Figs. 4–6 was Elabo-
rated using Mercury Program (Mercury 3.5.1 (Build RC5).
The structure of this crystal (Fig. 4) is almost planar since all of
the atoms, except C1, are essentially coplanar with a C7-C6-C8-C7
twist angle equal to 168.4 (5)° (Table 4).
The crystal stack is arranged in the form of parallel alternating
layers along the axis a. The C8H3O2Br5 molecules are assembled
by overlapping in a head-to-tail fashion following the π-π interac-
tions between the benzene rings in a stack along the direction of
the A axis presented in (Fig. 5) with a centroid-centroid distance
Fig. 5. Part of the crystal stack showing the π-π interactions between the benzene
rings along the A axis.
˚
equal to 3.722 (2) A.
The significant intramolecular interactions between the atoms
˚
O1 ··· O2 (Fig.6) (donor-acceptor distance of 2.578(5) A) are prob-
ping molecules head-to-tail due to the centroid-centroid interac-
tions between the benzene rings.
ably the main responsible for the stability of the molecular form
of this compound C1. The elongation of the hydrogen bond of the
brominated cycle C1 compared to that of brominated coumarin C2
˚
[12] (which has a donor-acceptor distance of 2.489 (6) A) was ex-
3.4. Hirshfeld surface analysis
plained by the mesomeric donor effect of the bromine atoms lo-
cated in the aromatic cycle which could increase the electronic
transfer. The stability of the structure was also ensured by in-
termolecular hydrogen bonds of O1—H2o1···O2i type between the
phenolic group of cycle 1 and the ketone group of another cycle,
through these bonds the molecules form parallel sheets along the
axis [10] (Fig. 6) The geometric organization of the structure in the
(101) plane can be described by the juxtaposition of the overlap-
Analysis of Hirshfeld surfaces (HS) suggest the possibility of ob-
taining additional insight into intermolecular interactions within
crystals. The Hirshfeld area graphs of the title compound C1 and
the brominated coumarin C2 [12] are shown in the Fig. 7, repre-
senting the areas, which have been mapped over dnorm, is scaled
between [-0.321, 0.121] (Fig. 7(A) b) and [-0.130, 1.111] (Fig. 7(B)
b), respectively and the shape index.
7

A. Brahmia, L. Bejaoui, J. Rolicek et al.
Journal of Molecular Structure 1248 (2022) 131313
Fig. 6. Crystalline arrangement of C8H3O2Br5 (C1), showing intermolecular interactions O-H ··· O (in blue dotted line) along the axis [10].
The dnorm parameter was displayed as a surface with a red-
white-blue, where the red dots highlight the short contacts, the
white areas represent the contacts around the van der Waals sep-
aration and the blue regions are devoid of close contacts [13].
The dnorm mapping on HS of two compounds (Fig. 7(A) b,
Fig. 7(B) b) shows a large visible circular depression (deep red
spots) seen on the surface. These depressions plead for the in-
teractions of hydrogen bonds (O-H… O) for both compounds. In
addition, the close contacts of type Br···Br, Br···H-C and Br···C are
present for compounds C1 and C2 by white areas on the dnorm
map. The shortest Br ... Br and C-H···Br interactions for compound
The representations associated with 2D fingerprints have pro-
vided quantitative information on the crystal structure [46]. The
contact enrichment ratios of the contacts were calculated in order
to highlight the contacts [47] liable to cause the crystal structure
were represented (Fig. 8).
The largest contribution to the overall crystal packing in the ti-
tle compound C1 is from the interactions Br···Br covered 40% of
the total surface. On the other hand, the brominated coumarin C2
reveals only 8.4% (Fig. 8c). In contrast, the interactions H···H show
a very small contribution of 1.4% of the SH (C1) and an average
contribution of 11.1% (C2). This significant contribution of Br···Br
interactions to the total Hirshfeld surface is due to the fact that
the majority of the molecular crystal surface is covered with Br
atoms. The Br···H / H···Br interactions are represented by two peaks
in the upper zone (Fig. 8e) with a contribution of 19% (C1) and
22.6% (C2).
˚
˚
C1 reveal a distance of approximately 3.716 A and 3.74 A respec-
tively (Fig. 7(A) a). The Br···Br interactions are also evidenced in
shape index for the both compounds Fig. 6(A) c, Fig. 6(B) c by a
red concave region around the acceptor brome atom and present a
complementary blue convex region around the donor brome atom.
The shape index indicates the presence of the π-π stack, which
consist of red triangles (concave regions) and blue triangles (con-
vex regions) for two compounds (marked by circles in red) [13].
The comparison of the shape index mapping between the bromi-
nated cycle C1 and the brominated coumarin C2 reveals that the
new compound has weak π-π stacking interactions. The 2D finger-
print traces confirm this deduction since the planar stack mainly
corresponds to contacts C···C which appear as a tower like shape
at the middle part of the fingerprint plot (Fig. 7). The analysis
of the fingerprint graphs shows that the interaction C···C has a
contribution to Hirshfeld surfaces of 4.2% for the brominated cy-
cle C1 and a very significant contribution of 12.5% for brominated
coumarin C2.
The contacts O···H
/
H···O have
a significant contribution
(Fig. 8b) for the brominated coumarin of 26.1% of SH compared to
the brominated cycle 9.7% which manifests itself by important in-
teractions due to the hydrogen bonds of O-H...O and C-H ... O. This
type of interaction is manifested as two sharp points pointing to
the lower left of the plot. The analysis of the 2D fingerprint plots
for the title compound shows the existence of contacts type C···Br /
Br···C (Fig. 7a) which are absent in the brominated coumarin crys-
tal C2 with a significant contribution of 12.1% of SH and appears
in the top middle of the plot in the form of characteristic wings.
The proportion of O···Br/Br···O interaction in the both compounds
can also be gained by Hirshfeld surface analysis with a significant
distribution in two-dimensional 12.4% (C1) and 12.8% (C2).
Fig. 7. The dnorm (b) and shape index (c) Hirshfeld surfaces of C1: (A) and C2: (B), the dotted lines designate the close contacts between (Br···Br: blue color, Br···H: red color
and Br···C green color).
8

A. Brahmia, L. Bejaoui, J. Rolicek et al.
Journal of Molecular Structure 1248 (2022) 131313
Fig. 8. Two-dimensional fingerprint plots of the two compounds C1 and C2 showing percentages of contacts contributing to the total Hirshfeld surface area of the molecules:
(a) all interactions, and delineated into (b) O···H/H···O, H/H, (c) Br···Br, (d) H···H, (e) Br···H and (f) C···C interactions.
group are predicted at 109.4° and 108.1°, for the C1 molecule.
3.5. Molecule structure
From Table 5, C1-C2-C3-C4, O9-C4-C5-Br18, C2-C3-C11-C12, and
The optimized structure with the atom numbers and the se-
lected geometric parameters have been given in Fig. 9 and Table 5,
respectively.
C4-C3-C11-O13 dihedral angles for the C1 molecule are calculated
in 0.0° as the planar. Besides, the O13-C11-C12-Br15, C3-C11-C12-
Br15, and C3-C11-C12-Br16 angles for the C1 molecule are deter-
mined at 118.7°, -61.3°, and 61.2°, respectively. For the C2 molecule,
C1-C2-C3-C4, O14-C9-C12-C18, C9-C12-C18-O21 and O17-C13-C12-
C18 torsion angles have been estimated as -0.0°, -0.6°, 2.8°, 1.2°;
C2-C3-C4-C9 and C3-C4-C9-O14 dihedral angles are predicted in -
179.7° with a small deviation from the planar angle. Also, the O16-
C13-C12-C18 (-179.2°) and C13-C12-C18-O21 (-176.6°) dihedral an-
gles for C2 molecule are deviated from the planar angle by -0.8°
and -3.4°, respectively. The O21-C18-C19-Br22 and O21-C18-C19-
Br23 dihedral angles for C2 molecule are calculated at 37.5° and
-86.0°, orderly. It can be said that the observed and calculated op-
timized parameters for each compound are compatible with each
other.
Accordingly, the ring bond lengths C1-C2 and C3-C4 with hav-
ing the sp2 hybridization for the C1 molecule have been calcu-
˚
˚
lated at 1.38 A and 1.43 A, respectively. On the other hand, C3-
C11 and C11-C12 bond lengths for the C1 molecule are predicted
˚
at 1.48 and 1.57 A. Addition, the C4-O9, C11-O13, and C9-H10
bond lengths for the C1 molecule are calculated at 1.33, 1.22 and
˚
0.98 A, respectively. The C1-Br17 and C5-Br18 bond lengths for the
˚
ring of the C1 molecule have been predicted at 1.91 and 1.90 A,
whereas the other C-Br lengths for the C1 molecule have been cal-
2
˚
culated in 1.96–1.98 A. As expected from the sp hybridization of
the central atoms, the C1-C2-C3 and C3-C4-C5 ring angles for the
C1 molecule have been calculated 120.7° and 118.6°; here, the hy-
droxyl group bonded to the C4 and Br18 atom connected to the
C5 are responsible for the distortion (with 1.4°) from the planar
120°. Besides, the C12-C11-O13 angle for the C1 molecule has been
calculated at 116.1° with a deviation of 3.9° from 120°. The C11-
C12-Br14 and Br14-C12-Br15 angles related to the bromomethyl
3.6. Frontier molecular orbital analysis
As known well, the FMO energies and appearances of them
have long been used successfully to get a foresight of the behav-
Fig. 9. The optimized structures of C1 and C2 molecules at B3LYP/6-311++G(d,p) level.
9

A. Brahmia, L. Bejaoui, J. Rolicek et al.
Journal of Molecular Structure 1248 (2022) 131313
Fig. 10. HOMO & LUMO (isoval:0.02) and MEP (isoval:0.0004) pilots of C1 and C2 molecules at B3LYP/6-11+G(d,p) level in the gas phase.
ior of both simple organic molecules [48–50] and complex systems
[51–53], as they provide very useful information about the reactiv-
ity of the relevant chemical species. In Table 6, calculated chemi-
cal reactivity descriptors for C1, C2 molecules and their protonated
forms B3LYP/6-311++G(d,p) level are presented as detailed. To ex-
plain stability, reactivity of molecules and to predict the directions
of chemical reactions, in the literature some electronic structure
principles known as Hard and Soft Acid-Base Principle (HSAB) [54],
Maximum Hardness Principle [55], Minimum Polarizability Princi-
ple and Minimum Electrophilicity Principle are available in the lit-
erature [56]. In the book entitled “Conceptual Density Functional
Theory and Its Application in the Chemical Domain” edited by Is-
lam and Kaya [29], these electronic structure principles and their
applications are presented as detailed. Chemical hardness is re-
ported as the resistance towards electron cloud polarization or de-
formation of chemical species and according to Maximum Hard-
ness Principle, hard molecules are more stable compared to soft
ones. It is apparent from Table 6 that the hardest among studied
molecules is C2 molecule. Minimum Polarizability Principle intro-
duced with the help of Maximum Hardness Principle states that
in a stable state polarizability (α) is minimized. Minimum Elec-
trophilicity Principle [55,57] states that the natural direction of a
chemical reaction is toward a state of minimum electrophilicity,
namely the molecules with low electrophilicity values are more
stable compared to others. It should be noted that both Minimum
Polarizability and Minimum Polarizability Principle support that C2
molecule is more stable than C1 molecule. As to conclude all elec-
tronic structure principles indicate the stability of C2 molecule.
Fig. 10 shows the HOMO, LUMO and MEP plots, which are com-
monly used to see the nucleophilic and electrophilic attack sites
for the molecular systems. For the C1 molecule, it is seen that
the HOMO, which implies the nucleophilic attack sites, is localized
over the ring part and >C=O group, whereas the LUMO that is in-
dicator of the electrophilic attack sites is localized over the whole
molecule, except for the Br14 and Br17 atoms. For the C2 molecule,
the HOMO density is over the rings and on Br23 atom, while the
LUMO density is around the whole molecular surface except for
the ketonic O17. On the other hand, the MEP plots have also pro-
vided information on the electron-rich and -poor regions of the
molecular systems by using the color scale based on the electro-
static potential of the system; the red color implies the electron-
rich region for the nucleophilic attack and blue color shows the
electron-poor region to electrophilic attacks. Accordingly, the red
color for the C1 molecule is around the oxygen atoms, the blue
color is around the C atoms bonded to the oxygen, H8 atom and
two bromine atoms. As expected from the NBO results, the red
color for the C2 molecule is over both the ketonic groups whereas
blue color is around the heteroatomic ring (Schema 1).
Schema 1. Synthesis of the brominated derivatives C1 and C2.
10

A. Brahmia, L. Bejaoui, J. Rolicek et al.
Journal of Molecular Structure 1248 (2022) 131313
4. Conclusion
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CRediT authorship contribution statement
Ameni Brahmia: Conceptualization, Writing – original draft,
Formal analysis, Writing – review & editing. Linda Bejaoui: Soft-
ware, Writing – review & editing. Jan Rolicek: Software, Writing –
review & editing. RachedBen Hassen: Methodology, Conceptualiza-
tion, Writing – review & editing. Goncagül Serdarog˘lu: Software,
Writing – review & editing. Savas¸ Kaya: Software, Writing – review
& editing.
Acknowledgment
The authors extend their appreciation to the Deanship of
Scientific Research at King Khalid University for funding this
work through
a research group program under grant number
R.G.P.1/141/40. The authors are also grateful to the Scientific and
Technological Research Council of Turkey (TUBITAK). All quantum
chemical calculations were performed at the High Performance and
Grid Computing Center (TR-Grid e-Infrastructure).
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