A Rapid Ultrasound Synthesis of Xanthenediones Catalyzed by Boric acid in Ethanol-Water Medium: Single Crystal, DFT and Hirshfeld Surface Analysis of Two Representative Compounds

Article abstract of DOI:10.1016/j.molstruc.2020.129794

A highly versatile and efficient ultrasound promoted synthesis of xanthenedione derivatives is achieved through condensation of dimedone with various aromatic aldehydes using boric acid as catalyst in ethanol-water medium. The advantages of this method be

Full text of DOI:10.1016/j.molstruc.2020.129794

Journal of Molecular Structure 1228 (2021) 129794
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
A Rapid Ultrasound Synthesis of Xanthenediones Catalyzed by Boric
acid in Ethanol-Water Medium: Single Crystal, DFT and Hirshfeld
Surface Analysis of Two Representative Compounds
R Shashia, Noor Shahina Beguma,∗, Anoop Kumar Pandayb
a Department of Studies in Chemistry, Bangalore University, Jnana Bharathi, Bangalore 560 056, Karnataka, India
b Department of Chemistry, Indian Institute of Technology, Patna, Bihta 801103, Bihar, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly versatile and efficient ultrasound promoted synthesis of xanthenedione derivatives is achieved
through condensation of dimedone with various aromatic aldehydes using boric acid as catalyst in
ethanol-water medium. The advantages of this method being, mild reaction conditions, short reaction
time, easy work-up, purification of products by non-chromatographic methods and additionally this
method provides excellent yields. Two of the Xanthendiones derivatives 3a and 3b gave good crystals on
recrystallization and their molecular structures were confirmed by crystallographic studies. The molecules
in the crystal lattice are held together by weak intermolecular C-H•••O and C-H•••N interactions. Fur-
ther insights into these interactions using Hirshfeld surface analysis and DFT/B3LYP studies show that in
compound 3a H•••H (54.7%), O•••H (18.3%) and in 3b H•••H (53.7%), O•••H (17.6%) are the major con-
tributors to the intermolecular interactions which stabilize the crystal structures. In order to determine
molecular electrical transport properties, we studied the energy difference between Highest Occupied,
HOMO, and Lowest Unoccupied, LUMO orbitals and the HOMO and LUMO energy gap for compounds 3a
and 3b was found to be 3.9261 eV and 4.6436 eV respectively. The 2D fingerprint plot provided percent-
age contribution of each individual atom-to-atom interactions. The Mulliken atomic charges and molecu-
lar electrostatic potential on molecular van der Waals surface were calculated to know the electrophilic
and nucleophilic regions of the molecular surface.
Received 14 November 2020
Revised 10 December 2020
Accepted 12 December 2020
Available online 19 December 2020
Keywords:
Xanthendione
boric acid
sonication technique
crystal structure
DFT studies and Hirshfeld surface analysis
© 2020 Elsevier B.V. All rights reserved.
1. Introduction
dyes [7,8], fluorescent probes for the visualization of biomolecules
[9], laser dyes [10] and corrosion inhibitors [11].
Design and development of an accessible procedure for the
synthesis of simple heterocycles with various functionalities is
a worthwhile contribution in organic synthesis. Xanthendiones
are important structural units in heterocyclic class of compounds
which have been widely investigated in recent years. In particular,
the xanthenedione moiety is present in several natural products
[1] and they are also valuable synthons because of the inherent re-
activity of their pyran ring [2]. Synthesis of xanthenedione deriva-
tives has been of considerable interest to chemists, due to their
wide application in medicine and pharmaceutics such as antivi-
ral [3], antibacterial agents [4], photosensitizers for photodynamic
therapy, antagonists of zoxazolamine [4,5], and anti-inflammatory
drugs [6]. Furthermore, xanthenes are also reported as staining
A large number of organic reactions that have been carried out
under ultrasonic irradiation require short reaction time and in-
volves easier work-up procedures than conventional methods and
above all are known to give higher yields [12]. Ultrasound provides
an unusual mechanism for generating high-energy chemistry. Ul-
trasound works on the phenomenon of cavitation; which involves
the growth, oscillation, and collapse of bubbles under the action of
an acoustic field.
Owing to their unique biological profile, numerous method-
ologies have been developed for the synthesis of xanthenediones.
Many such catalysts, for example are InCl3.4H2O [13], NaHSO4•SiO2
2–
[14], silica sulfuric acid [15], TiO2/SO4
[16], ZrOCl2•8H2O [17],
FeCl3•6H2O [18], Dowex-50W [19], Fe3+-montmorillonite [20],
amberlyst-15 [21] and alumina sulfuric acid [22] as solid acid cat-
alysts. In addition, the synthesis of other xanthenedione deriva-
tives, catalyzed by a Preyssler-type heteropoly acid [23], HPA/SiO2
[24] and HPWA/ MCM-41 [25] have also been reported.
∗
Corresponding author.
E-mail
addresses:
noorsb05@gmail.com,
noorsb@bub.ernet.in,
noorsb@rediffmail.com (N.S. Begum).
https://doi.org/10.1016/j.molstruc.2020.129794
0022-2860/© 2020 Elsevier B.V. All rights reserved.

R. Shashi, N.S. Begum and A.K. Panday
Journal of Molecular Structure 1228 (2021) 129794
Scheme 1. Syntheses of xanthenediones using boric acid in ultrasound condition.
However, many of the reported protocols are, although effi-
cient, a few of them suffer from serious drawbacks such as tedious
preparation of the catalyst, high reaction temperature, longer reac-
tion time, low yields, excess use of reagents as well as toxicity of
catalysts or cost of catalysts. Among the numerous methods for the
synthesis of xanthenediones, the condensation of aldehydes with
active methylene compound like dimedone in the presence of boric
acid as a catalyst is found to be very efficient. In recent years, boric
acid has gained special attention as catalyst in organic synthesis
because of its many advantages associated with this acid, such as
excellent solubility in water, uncomplicated handling, inexpensive-
ness and eco-friendly nature.
by thin-layer chromatography (TLC) and after completion of the re-
action, the mixture was cooled to room temperature and filtered.
The precipitate obtained was washed with water. The crude prod-
uct was further recrystallized using ethanol as the solvent.
4. Investigation techniques
4.1. X-ray single crystal structural analysis
The X-ray diffraction data, for the compounds 3a and 3b were
collected on a Bruker Smart CCD Area Detector System using MoKα
˚
(0.71073 A) radiation in ω − φ scan mode. The data were reduced
using SAINT-Plus [26]. The structure in each case was solved by Di-
rect Methods and refined on F2 using SHELX-97 [27] package. All
the non-hydrogen atoms were refined anisotropically. As the hy-
drogens were not readily revealed from difference Fourier maps,
they were included in the ideal positions with fixed isotropic U
values and they were riding with their respective non-hydrogen
atoms. The difference Fourier map, after the refinement, was es-
sentially featureless in all cases. The mean plane calculations were
done using the program PARST [28]. Diagrams and publication ma-
terial were generated using ORTEP-3 [29] and PLATON [30].
In pursuit of our work to develop environmentally friendly
synthetic methodologies for the synthesis of xanthenediones, the
present work is envisioned as the green chemistry approach using
water-ethanol solvent system for ultrasound mediated domino re-
action in efficient synthesis of xanthenediones. To the best of our
knowledge, boric acid (BO3H3 or B (OH)3) has not been used as a
catalyst for the synthesis of xanthendiones and has attracted our
attention to investigate the application of boric acid as a catalyst.
The environmental impact is reduced by the fact that all reactions
are carried out in water-ethanol system and are ultrasound medi-
ated reactions which has easy work up, a greener solvent, shorter
reaction time and hence a complete green approach.
4.2. Computational details
Compound 3a and 3b were theoretically explored in detail for
the comparative investigation with experimentally obtained results
of X-ray diffraction. All calculations were performed by Gaussian
16 software package [31] and were visualized using GaussView 6
without any constraints on the geometry [32]. Density Functional
Theory (DFT) calculations were performed using B3LYP functional
proposed by Becke [33-34] and Lee, Yang, Parr with all electron
pople 6-311+G (d,p) basis set [35-36] as implemented in the Gaus-
sian 16 package. All the structure were optimized without any con-
straints. The structure has been characterised as minima on poten-
tial energy surface (PES) by performing harmonic vibration anal-
ysis. The molecular orbital energies were calculated using the 6-
311+G (d,p) basis set. No symmetry constraints were applied and
only the default convergence criteria were used during the geo-
metric optimizations. In addition to this, Molecular electrostatic
potential map (MEP) was obtained from the output of B3LYP/6-
311+G (d,p) basis set.
2. Materials and instruments
All reactions were performed in oven dried apparatus. All the
chemicals were purchased from Sigma-Aldrich and Spectrochem-
India. Reactions were monitored on Merck F-254 pre-coated TLC
plastic sheets using hexane as mobile phase. Melting points were
determined by the open capillary method using Guna melting
point apparatus and remain uncorrected. IR spectra were recorded
on a Shimadzu FT-IR 8400S spectrometer and the values are re-
ported in wave number (cm−1). 1H NMR and 13C NMR were
obtained on a Bruker AMX 400 spectrometer using CDCl3 with
tetramethylsilane as internal standard. Mass spectra were recorded
on Finnigan MAT (Model MAT8200) spectrometer. Ultrasonication
was performed using SIDILU, sonic bath working at a constant fre-
quency of 35 kHz and an output power of 70W at 26˚C (main-
tained by circulating water). The reactions were performed in open
vessels without any mechanical stirring.
5. Results and Discussions
3. Experimental
5.1. Chemistry of Xanthenediones
3.1. General procedure for synthesis of xanthendiones
We initiated our investigation by carrying out a comparative
study between the conventional reflux method versus sonication
technique. The study was attempted by using a model reaction be-
tween 4-hydroxy benzaldehyde and dimedone in presence boric
acid as catalyst at 60°C under reflux condition and a similar re-
action in sonicator maintained at 26°C. Once the reactions were
A mixture of various aromatic aldehydes (1 mmol), dimedone
(2 mmol), and catalytic amount of boric acid was added in a round
bottom flask with a 1:1 mixture of ethanol-water solvent system
and placed in a sonic bath and sonicated at room temperature un-
til the reaction was complete Scheme 1. Reactions were monitored
2

R. Shashi, N.S. Begum and A.K. Panday
Journal of Molecular Structure 1228 (2021) 129794
Table 1
Effect of catalyst on sonication reaction.
Trial No.
Reaction carried out by sonication at 26°C.
Duration (mins)
%Yield obtained
1.
2.
3.
Reaction carried out in absence of catalyst
Reaction catalysed by conc. HCl
170
130
50
60
73
Reaction catalysed by boric acid
95(3c)
Table 2
tion with intermediate (3) further, the condensed intermediate fur-
nishes the products 3a–j by the loss of water molecule.
Optimisation of solvent for the synthesis of Xanthene-
dione derivatives in ultrasound conditions.
Entry
Solvent
Time(mins)
Yield (%)a
5.2. Crystallographic Studies
1.
2.
3.
4.
5.
6.
CH3CN
130
115
90
76
76
85
75
85
95
CHCl3
5.2.1. Compound (3a)
CH2Cl2
Intensity data were collected at 298 K in the ω-φ scan mode.
A total of 19545 reflections were collected, resulting in 5497 [R
(int) = 0.0653] independent reflections, of which the number of
reflections satisfying I > 2σ(I) criteria were 5497. The R factor for
observed data finally converged to R1 = 0.0638.
Water
80
C2H5OH
C2H5OH- Water
75
50
∗a Yields refer to pure isolated product
5.2.2. Compound (3b)
completed it was observed that the reaction carried out in re-
flux condition had a serious drawback over the sonicated reaction
mixture in terms of its reaction duration, purity and in product
yield. Reflux reaction was carried out at 60°C which gives a yield
of 74% in 7-8 hours, whereas the reaction carried out by sonica-
tor at 26°C was almost completed within 50 minutes with a yield
of 95%. Therefore, we opted for sonication technique at 26°C in
ethanol. Further, in order to study the importance of boric acid
as the catalyst we conducted a model reaction between 4-hydroxy
benzaldehyde and dimedone at 26°C in one-pot using two differ-
ent types of catalyst simultaneously at the same time. Initially, the
reaction (Table 1, trial 1) was carried out in absence of the cata-
lyst and the reaction was found to go to completion after a longer
duration of 170 mins with much lesser yield of 60%. In trial 2
we carried out the same reaction with catalytic amount of con-
centrated hydrochloric acid and in trial 3 the reaction was car-
ried out in presence of boric acid as the catalyst, both the re-
actions were sonicated in ethanol. Once the reaction was com-
pleted the yield of the product was found to be more in case of
boric acid along with less by-products, easy eco-friendly workup
with water, less tedious process and the product was formed in
shorter duration when compared with conc. HCl. (Table 1) The
desired product was isolated as a white crystalline solid in 95%
yield after 50 mins. Hence, considering the advantages of boric
acid as the catalyst in sonication, the first of its kind method
has been reported here. Later the same reaction was optimised
with different solvents and highest yields were obtained in water-
ethanol system. (Table 2) Hence, we carried out all the reactions
under the same reaction conditions that afforded the desired prod-
ucts in higher yields with different substituents (Table 3). Interest-
ingly, the aryl aldehydes containing either electron-withdrawing or
electron-donating substituents reacted smoothly and provided the
desired products in good to excellent yields. High yields were ob-
tained when the reaction was carried out with electron-donating
groups such as p-hydroxybenzaldehyde, p-methoxybenzaldehyde,
p-chlorobenzaldehyde and p-bromobenzaldehyde. (3c, 3h, 3d and
3f) However, electron-withdrawing substituents afforded moderate
yields when reaction was carried out with m-cyanobenzaldehyde
and p-cyanobenzaldehyde. (3a and 3b) (Table 3) A plausible mech-
anism for the synthesis xanthenedione is shown below (Fig. 1)
with boric acid as the bronsted acid catalyst. Initially activation of
substituted benzaldehyde (1) takes place with boric acid followed
by attack of enol form of dimedone (2) to give intermediate (3) by
loss of water molecule through Clasien-condensation mechanism.
Later the second molecule of dimedone undergoes Micheal addi-
Intensity data were collected at 293 K in the ω-φ scan mode.
A total of 17535 reflections were collected, resulting in 4044 [R
(int) = 0.0289] independent reflections, of which the number of
reflections satisfying I > 2σ(I) criteria were 4044. The R factor for
observed data finally converged to R1 = 0.0446.
The ORTEP view of the molecules 3a and 3b with atom labelling
is shown in Fig. 2. Packing of molecules for compound 3a and 3b is
shown in Fig. 3 and 4. Summary of crystallographic data and other
structure refinement parameters of the compounds 3a and 3b are
given in Table 4. Table 5 gives the other weak interaction param-
eters in compound 3a and Table 6 gives weak interaction parame-
ters for compound 3b.
Compounds 3a and 3b crystallize in the triclinic and or-
thorhombic crystal system with one and four molecules in the
asymmetric unit respectively. Both 3a and 3b the xanthene rings
are similar but they differ in the position of cyano group on the
phenyl ring, 3a contains 3-cyano phenyl ring whereas 3b contains
4-cyano phenyl ring as substituents. In compound 3a and 3b the
aryl ring is positioned axially to the xanthene ring with a dihedral
angle of 87.83˚ and 89.91˚ respectively. Aryl rings in both the com-
pounds are projected away from the plane of the xanthene ring.
In
compound
3a,
the
central
pyran
ring
B
(O1/C8/C9/C16/C17/C24) of the xanthene moiety is in boat
˚
conformation, with atoms C8 and O2 displaced by 0.124(2)A
˚
and 0.103(0)A, respectively from the mean plane of the other
four atoms (C9/C16/C17/C24) and the two outer rings, ring A
(C17/C18/C19/C22/C23/C24), and ring C (C9/C10/C11/C12/C15/C16)
are in sofa conformations. The two cyclohexenone rings adopt sofa
˚
conformation in ring A, C19 atom lies 0.592(4) A above the plane
from the remaining 5 atoms of the ring A (C17/C18/C22/C23/C24)
˚
and in ring C, C12 atom by 0.618(5) A above the plane of the
remaining 5 atoms of the ring (C9/C10/C11/C15/C16).
In compound 3b the central pyran ring of the xanthene moi-
ety adopts boat conformations with O1 and C9 atoms displaced
˚
˚
by 0.085A and 0.185 A respectively from the mean plane of the
other four atoms C1/C6/C9/C10/C15 and the two cyclohexenone
rings adopt sofa conformation. Ring A (C1/C2/C3/C4/C5/C6), shows
˚
sofa conformation with C4 atom displaced by 0.645(4)A from the
remaining 5 atoms of the ring (C1/C2/C3/C5/C6) similarly, in ring
C (C10/C11/C12/C13/C14/C15) sofa conformation is observed with
˚
C13 atom displaced by 0.625(4)A from the remaining 5 atoms of
the ring C10/C11/C12/C14/C15. The crystal structure of 3a is sta-
bilised by one C-H•••N and one C-H•••O intermolecular interac-
tions (Fig. 3), whereas the crystal structure of 3b is stabilised only
by three C-H•••O intermolecular interactions (Fig. 4).
3

R. Shashi, N.S. Begum and A.K. Panday
Journal of Molecular Structure 1228 (2021) 129794
Table 3
Isolated Yields and time duration for formation of 9-aryl-1H-xanthendiones 3a–3j.
Compound Codes. Compounds Yield (%) Time(mins)
Obs. mp(˚C)
Lit. mp(˚C) [Ref]
3a.
3b.
3c.
85
60
204-206
[-]
88
55
205–207
[-]
95
50
204-206
(205-207 [41])
3d.
91
50
232–234
(231–233 [42])
3e.
93
55
172-174
(170-172 [43])
3f.
98
60
224-226
(226-227 [41])
3g.
86
55
225-227
(224-225 [41])
(continued on next page)
4

R. Shashi, N.S. Begum and A.K. Panday
Journal of Molecular Structure 1228 (2021) 129794
Table 3
(continued)
3h.
96
50
259-261
(261-263 [41])
3i.
81
55
185-187
(182-183 [41])
3j.
86
70
173–175
(170-172 [41])
Fig. 1. A plausible mechanism for the formation of xanthenedione with boric acid 3a-j.
5

R. Shashi, N.S. Begum and A.K. Panday
Journal of Molecular Structure 1228 (2021) 129794
Table 4
Crystal data and refinement parameters for compounds 3a and 3b.
Compound code
3a
3b
CCDC No.
1918601
C24 H25 N O3
375.45
1960240
C24 H25 N O3
375.45
Empirical formula
Formula weight
Temperature K
298(2)
293K
˚
˚
Wavelength A
0.71076
Triclinic
P-1
0.71073 A
Crystal system
space group
Orthorhombic
Pbcn
˚
a [A]
7.546(5)
10.604(9)
13.753(10)
87.57
15.4678(5) A
10.9796(4) A
24.2521(8) A
90
˚
b [A]
˚
c [A]
α(o)
β(o)
γ (o)
78.28
90
73.67
90
−3
˚
Volume A
1034.0(1)
2
4118.7(2)
8
Z
Calculated density Mg/m3
F(000)
1.206
1.211
400
1600
Theta range/ (°) deg.
Limiting indices
2.96 to 29.10
-9<=h<=10,
-14<=k<=14,
-18<=l<=18
20161 / 5497
0.0653
3.33 to 26.00
-19<=h<=15,
-13<=k<=12,
-25<=l<=29
17535 / 4044
0.0289
Reflections collected / unique
R(int)
Completeness to theta
99.7 %
99.8
Max. and min. transmission
Data / restraints / parameters
Goodness-of-fit on F2
0.997 and 0.988
5497 / 0 / 258
1.018
% 0.9760 and 0.9744
4044 / 0 / 257
1.048
Final R indices [I>2sigma(I)]
R1 = 0.0638,
R1 = 0.0446,
R1
wR2 = 0.1285
wR2 = 0.1095
R indices (all data) R1
R1 = 0.1504,
R1 = 0.0766,
wR2 = 0.1613
wR2 = 0.1211
Largest diff. peak and hole
0.190 and -0.207
0.136 and -0.136
−3
˚
(e. A
)
Table 5
in between -0.1426au (blue) to 1.7279au (red) respectively for the
compound 3a and -0.2719au (blue) to 1.4982au (red) respectively
for the compound 3b.
˚
Non-bonded interactions and possible hydrogen bonds (A) for com-
pound 3a (D-donor; A-acceptor; H-hydrogen).
• • •
• • •
• • •
• • •
D—H A
D—H
A
D—H
H
A
D
A
The intermolecular interactions in compound 3a and 3b are
visualized by mapping the HS with different properties like de,
dnorm, curvedness mapped, fragment patch mapped, and shape in-
dex in Fig. 5 and 6 [44]. In HS with the dnorm (Fig. 5 and 6) white
colour surface indicate the contacts with the distances equal to the
sum of the van der Waals radii and the red and blue colour indi-
cate the distances shorter and longer than the van der Waals radii
respectively.
C3-H3ˑˑˑO3i
C22-H22BˑˑˑN1i
0.930
0.970
3.438
3.588
2.553
2.720
159.16
149.39
Symmetry codes: (i) -x+2,-y+1,-z.
Table 6
˚
Non-bonded interactions and possible hydrogen bonds (A) for com-
pound 3b. (D-donor; A-acceptor; H-hydrogen).
• • •
• • •
• • •
• • •
D—H A
D—H
A
D—H
H
A
D
A
All the percentages of the 2D fingerprint plot for compound 3a
and 3b are shown in (Fig. 7). Fig. 8 and 9 represents two dimen-
sional fingerprint plots (FP) with de and di distances in the range
C5-H5AˑˑˑO2i
C20-H20AˑˑˑO3ii
C12-H12BˑˑˑO2iii
0.970
0.930
0.970
2.690
2.388
2.612
3.605
3.275
3.565
157.48
159.29
148.07
˚
0.6-2.4A displaying different intermolecular interactions. Where di
is the closest internal distance from a given point on the Hirsh-
feld surface and de is the closest external contacts. The finger print
reveals the contribution of each individual intermolecular contact
to the surface which can be identified through colour codes (fre-
quency of presence). If di > de then this represents the dark re-
gions on the surface are due to interaction of hydrogen bond ac-
ceptors. Similarly, the regions with de > di value are due to the hy-
drogen bond acceptors. The white colour indicates no occurrence,
blue indicates some occurrence, green and red indicates more fre-
quent occurrence of any given (di, de) pair. From the total contri-
butions for both compounds 3a and 3b the H-H contacts has max-
imum and O-C has minimum contributions. Similarly the C-H, O-H
and N-H contacts also contribute to the total area of the surface as
shown in Fig. 7 for both compound 3a and 3b. Fig. 10
Symmetry codes: (i) -x+1/2, -y-1/2, +z (ii) –x+1, -y+1, -z+1 (iii)
x+1/2, -y+1/2, -z+1
5.3. Hirshfeld surface analyses
In order to study the intermolecular interactions in compound
3a and 3b, Hirshfeld surface (HS) analysis and related 2D finger
plots were calculated using Crystal Explorer 17 [37] by submitting
the crystallographic information file (CIF) of compounds 3a and 3b.
Surface features which are characteristic of different types of inter-
molecular interactions can be identified and these features can be
visualized by colour coding distances from the surface to the near-
est atom exterior (de plots) or interior (di plots) [38-40]. The dnorm
mapped on the Hirshfeld surfaces were generated with colour scale
6

R. Shashi, N.S. Begum and A.K. Panday
Journal of Molecular Structure 1228 (2021) 129794
The contributions of different atoms are shown in (Fig. 7). The
higher amount of H•••H interactions in these compounds show
that van der Waals interactions also plays a major role in the crys-
tal packing (Fig. 3 and 4). Interestingly, here we have found that
in compound 3a fingerprint plots of O•••N, and N•••N were not
found (Fig. 7). Consequently, the contact analysis for the compound
3a and 3b suggests that the C-H•••O hydrogen bonds are the driv-
ing force in molecular arrangement and crystal packing formation.
5.4. Molecular geometry optimizations
The structure of the compounds 3a and 3b was optimized
by DFT calculations using the B3LYP hybrid functional with 6-
311+G (d, p) basis set. The comparison of selected optimized ge-
ometrical parameters such as bond length, bond angle, and tor-
sion angle, with those parameters obtained from XRD studies, are
listed in supplimentary file (Tables 7-12). The minor deviations ob-
served between the theoretically calculated and experimentally de-
termined values can be accounted for the differences in the molec-
ular environment between the crystalline phase and gas phase.
5.5. Frontier molecular orbital analysis
HOMO and LUMO orbitals of compounds 3a and 3b are shown
in Fig. 11 and 12 respectively.
Molecular orbital energy and frontier molecular orbital energy
levels are calculated by 6-311+G (d.p) level. The obtained energy
values are in atomic units (a.u.) and those values have been con-
verted into electron volt (eV) by making use of the conversion fac-
tors as 1 a.u. = 27.211396132 eV. The calculated HOMO and LUMO
energies were found to be -6.1239 eV and -2.1978 eV respectively
and energy gap of 3.9261 eV for compound 3a whereas for the
compound 3b HOMO and LUMO energies are -6.9135 eV and -
2.2699 eV respectively and energy gap is 4.6436 eV. This large en-
ergy gap value for the compound 3b is an assertion for its high
stability.
The energy difference between the HOMO and LUMO orbitals
is called the energy gap (ꢀE) which is 3.9261 eV and 4.6436 eV
for the compound 3a and 3b respectively, which is important in
expecting the stability and reactivity of the compound. If the gap
is large the compound is expected to have high stability and low
reactivity whereas when the gap is small the compound is ex-
pected to have less stability and high reactivity [45]. The impor-
tance of the FMOs is in determining the electronic properties, op-
tical properties, and chemical reactions. The energy of the highest
occupied molecular orbital (HOMO) is related to the ionization po-
tential while the energy of the lowest unoccupied molecular or-
bital (LUMO) is related to the electronic affinity.
Fig. 2. ORTEP view of compounds 3a and 3b, showing 50% probability ellipsoids
and the atom-numbering scheme.
The typically important global reactivity parameters related to
frontier molecular orbital energies such as chemical hardness (η),
electronegativity (χ), electronic chemical potential (μ), global elec-
trophilicity index (ω) were calculated from HOMO-LUMO energy
values from equations [46]. The magnitude of global reactivity de-
scriptor values are tabulated in (Table 13).
Fig. 7 clearly indicates that, intermolecular interactions con-
tributed by O•••O, O•••C, O•••H, C•••N, C•••H, C•••C, H•••H and
N•••H, the maximum contribution are given by H•••H (54.7%)
and O•••H (18.3%) followed by N…H (13.3%), C•••H (9.8%), C•••
C
5.6. Atomic charge analysis
(3.4%), C•••N (0.3%), O•••O (0.1%) and O•••C (0.1%) in compound
3a. However in compound 3b, intermolecular interactions are con-
tributed by O•••O, O•••C, O•••H, O•••N, C•••N, C•••H, C•••C,
H•••H, N•••H, and N•••N, the maximum contribution are given
by H•••H (53.7%) and O•••H (17.6%) followed by C•••H (14.5%),
The Mulliken charge distributions for the compounds have been
calculated using 6-311+G (d,p) level shown in (Table 14 and 15). In
the compounds 3a and 3b the magnitude of the carbon Mulliken
charges, was found to be either positive or negative, ranging from
-1.257 and 1.572 for the compound 3a and -1.630 to 2.141 for the
compound 3b. The most positive charge is over carbon (C4=1.572)
atom in compound 3a and (C21= 2.141) atom in compound 3b. The
nitrogen and oxygen atoms have negative charges.
N•••H (10.8%),O•••N (1.0%), C•••C (0.7%), O•••O (0.6%), C•••
N
(0.6%), N•••N (0.4%) and C•••O (0.1%). The inter contact distances
obtained from Hirshfeld analysis are in good correlation with the
single crystal analysis.
7

R. Shashi, N.S. Begum and A.K. Panday
Journal of Molecular Structure 1228 (2021) 129794
•••
•••
O interactions.
Fig. 3. Packing of the compound 3a showing intermolecular C-H
N and C-H
5.7. Molecular electrostatic potential analysis
The molecular electrostatic potential (MEP) analysis can be re-
garded as a powerful tool for identifying the possible interaction
sites around a molecule. One of the most interesting features of
quantum chemistry is the ability to explain the reactivity of com-
pounds under investigation. It determines the reactivity of a chem-
ical system by predicting electrophilic as well as nucleophilic sites
in target molecules. The computed MEP using 6-311+G (d,p) level
of DFT is shown in (Fig. 13) The MEP surface allows us to vi-
sualize the various regions of a molecule. The charge distribu-
tion helps to determine the molecular interaction and the nature
of the chemical bond. The positive area of the MEP is a nucle-
ophilic site, while the negative region is associated with an elec-
trophilic site. The (Fig. 13) shows the negative charges are more
and they are concentrated around the nitrogen atom. The colour
code of the map is in the range between -6.280 × 10−2 a.u. (Deep-
est red) and -6.280 × 10−2 a.u. (Deepest blue) in compound 3a and
-5.901 × 10−2 a.u. (Deepest red) and 5.901 × 10−2 a.u. (Deepest
blue) in compound 3b in the maps, the most negative region on
the MEP surface of the compound 3a and 3b are associated with
the lone-pairs of the nitrogen atom.
6. Conclusion
•••
O interactions.
Fig. 4. Packing of the compound 3b showing intermolecular C-H
In conclusion, the present method is an operationally simple
and clean procedure for the synthesis of xanthenediones using a
Fig. 5. dnorm mapped, curvedness mapped, fragment patch mapped and shape index mapped on Hirshfeld surface respectively of the compound 3a.
8

R. Shashi, N.S. Begum and A.K. Panday
Journal of Molecular Structure 1228 (2021) 129794
Fig. 6. dnorm mapped, curvedness mapped, fragment patch mapped and shape index mapped on Hirshfeld surface respectively of the compound 3b.
Fig. 7. Percentage of finger prints plots of selected interactions of compound 3a and 3b.
Fig. 8. Finger print plots of selected interactions of compound 3a.
MS, 1H and 13C NMR and two representative compounds 3a and
catalytic amount of boric acid. In addition, the low cost, easy avail-
ability, low toxicity, moderate Lewis acidity and moisture com-
patibility of the catalyst, excellent yields of products, water sol-
ubility and short reaction time makes this methodology a valid
contribution to the existing processes in the field of synthesis of
xanthenedione derivatives. Xanthenedione derivatives were further
characterized by means of various spectroscopic tools like ESI-
3b were confirmed by single crystal X-ray diffraction studies. The
molecular structure is stabilized by intermolecular N–H…O and C–
H…O hydrogen bonds. The three dimensional dnorm and 2D finger-
print plots from Hirshfeld were studied extensively to understand
the intermolecular interactions. The Hirshfeld surface analysis dis-
close that H-H interactions have maximum contribution to the in-
9

R. Shashi, N.S. Begum and A.K. Panday
Journal of Molecular Structure 1228 (2021) 129794
Fig. 9. Finger print plots of selected interactions of compound 3b.
Fig. 10. DFT optimized molecular structure of the compound 3a and 3b.
Table 13
The energy values of global reactivity descriptors.
Parameter
Compound 3a Value in eV
Compound 3b Value in eV
ELUMO
-2.1978
-6.1239
3.9261
1.9630
4.1608
-4.1608
0.2547
4.4096
-2.2699
-6.9135
4.6436
2.3218
4.5917
-4.5917
0.2153
4.5403
EHOMO
ꢀE
Chemical Hardness(η)
Electronegativity(χ)
Chemical Potential (μ)
Chemical Softness(s)
Global electrophilicity index(ω)
termolecular interactions. Further, the molecule was geometrically
optimized using B3LYP/ 6-31G (d,p) level of theory. The Mulliken
atomic charges and MEP were analysed for the nucleophilic and
electrophilic regions of the molecular surface. The HS and MEP
analysis indicated the presence of a strong C-H…O hydrogen bond
formation. While the 2D fingerprint plot provides percentage con-
tribution of each individual atom-to-atom interactions. Moreover,
the HOMO-LUMO energy gap suggests a good stability of these
compounds. The correlation between the bond lengths and bond
angle parameters obtained from crystallographic studies and from
theoretical calculations are in good agreement with the optimized
structures.
10

R. Shashi, N.S. Begum and A.K. Panday
Journal of Molecular Structure 1228 (2021) 129794
Fig. 12. HOMO-LUMO orbitals of compound 3b.
Table 14
Atomic charge analysis for compound 3a.
Fig. 11. HOMO-LUMO orbitals of compound 3a.
Atom
Mulliken charge
Atom
Mulliken charge
C1
-0.645
-0.371
-0.348
1.572
-1.257
-0.242
1.33
C13
C14
C15
C16
C17
C18
C19
C20
C21
C22
C23
C24
O3
-0.504
-0.473
-0.34
C2
C3
7. Supplementary data
C4
-0.487
-0.362
-0.426
0.475
C5
C6
Supplementary crystallographic data for this article in CIF for-
mat are available at the Electronic Supplementary Publication from
Cambridge Crystallographic Data Centre (CCDC Nos: 3a 1918601
and 3b 1960240). This data can be obtained free of charge http:
//www.ccdc.cam.ac.uk/conts/retrieving.html, from the Cambridge
Crystallographic Data Centre, 12 Union Rood, Cambridge CB2 1EZ,
UK (Fax: (international): +44 1223/336 033; email: deposit @
ccdc.cam.ac.uk).
C7
C8
0.278
0.521
-0.415
-0.636
0.306
-0.214
-0.39
-0.447
-0.509
-0.594
-0.23
C9
C10
C11
C12
O1
O2
0.555
-0.233
-0.197
N1
Fig. 13. MEP surface of the compound 3a and 3b respectively.
11

R. Shashi, N.S. Begum and A.K. Panday
Journal of Molecular Structure 1228 (2021) 129794
Table 15
[12] T.J. Mason, D. Peters, Practical Sonochemistry, Ellis Horwood, New York, 1991.
Atomic charge analysis for compound 3b.
•
[13] X. Fan, X. Hu, X. Zhang, J. Wang, InCl3 4H2O-promoted green preparation of
xanthenedione derivatives in ionic liquids, Canadian Journal of Chemistry 83
(2005) 16–20.
Atom
Mulliken charge
Atom
Mulliken charge
[14] B. Das, P. Thirupathi, K.R. Reddy, B. Ravikanth, L. Nagarapu, An efficient syn-
thesis of 1,8-dioxo-octahydroxanthenes using heterogeneous catalysts, Cataly-
sis Communication 8 (2007) 535–538.
[15] M. Seyyedhamzeh, P. Mirzaei, A. Bazgir, A. Solvent-free synthesis of
aryl-14H-dibenzo [a,j]xanthenes and 1,8-dioxo-octahydro-xanthenes using sil-
ica sulfuric acid as catalyst, Dyes and pigments 76 (2008) 836–839.
[16] T.S. Jin, J.S. Zhang, A.Q. Wang, T.S. Li, solid-State Condensation Reactions Be-
tween Aldehydes and 5,5-Dimethyl-1,3-cyclohexanedione by Grinding at Room
Temperature, Synthetic Communications 35 (2005) 2339–2345.
C1
0.885
-0.573
-0.512
0.356
-0.45
C10
C11
C12
C13
C14
C15
C16
C17
C23
O3
0.885
-0.573
-0.513
0.356
-0.45
C2
C3
C4
C5
C6
-0.55
-0.55
C7
-0.506
-0.501
0.261
-0.209
1.177
0.136
-0.588
-0.033
-0.506
-0.501
-0.087
-0.209
2.141
-1.006
-1.63
C8
•
C9
[17] E. Mosaddegh, M.R. Islami, A. Hassankhani, ZrOCl2 8H2O as an efficient and
O2
C18
C19
C20
O1
recyclable catalyst for the clean synthesis of xanthenedione derivatives under
solvent-free conditions, Arabian Journal of Chemistry 5 (2012) 77–88.
C21
C22
C24
N1
•
[18] X.S. Fan, Y. Zhen, X.Y. Zhang, X.Y. Hu, Wang, FeCl3 6H2O Catalyzed Reaction
of Aromatic Aldehydes with 5,5-Dimethyl-1,3-cyclohexandione in Ionic Liquids,
Chinese Chemical. Letters 16 (7) (2005) 897–899.
-0.189
[19] G. Imani-Shakibaei, P. Mirzaei, A. Bazgir, Dowex-50W promoted synthesis of
14-aryl-14H-di benzo [a,j]xanthene and 1,8-dioxo-octahydroxanthene deriva-
tives under solvent-free conditions, Applied. Catalysis A 325 (2007) 188–192.
[20] G. Song, B. Wang, H. Luo, L. Yang, Fe3+-Montmorillonite as a cost-effective and
recyclable solid acidic catalyst for the synthesis of xanthenediones, Catalysis
Communication 8 (2007) 673–676.
Declaration of competing interest
[21] B. Das, P. Thirupathi, I. Mahender, V.S. Reddy, Y.K. Rao, Amberlyst-15: An ef-
ficient reusable heterogeneous catalyst for the synthesis of 1,8-Dioxo Octahy-
droxanthenes and 1,8-Dioxo-Decahydroacridinesao, Journal of Molecular Catal-
ysis. A: Chemical 247 (2006) 233–239.
The author declare that they have no known competing finan-
cial interests or personal relationships that could have appeared to
influence the work reported in this paper
[22] A. Pramanik, S. Bhar, Alumina-sulfuric acid catalyzed eco-friendly synthesis of
xanthenediones, Catalysis. Communications 20 (2012) 17–24.
[23] M.M. Heravi, K. Bakhtiari, Z. Daroogheha, F.F. Bamoharram, Facile heteropoly-
acid-promoted synthesis of 14-substituted-14-H-di benzo[a,j] xanthene deriva-
tives under solvent-free conditions, Journal of Molecular Catalysis. A: Chemi-
cal. 273 (2007) 99–101.
CRediT authorship contribution statement
[24] M.M. Amini, M. Seyyedhamzeh, A. Bazgir, Heteropolyacid: An efficient and
eco-friendly catalyst for the synthesis of 14-aryl-14H-di benzo[a,j]xanthene,
Applied Catalysis 323 (2007) 242–245.
R Shashi: Conceptualization, Methodology, Writing - original
draft, Investigation, Software. Noor Shahina Begum: Supervision,
Visualization, Validation. Anoop Kumar Panday: Formal analysis.
[25] G. Karthikeyan, A. Pandurangan, Heteropolyacid (H3PW12 O40
) supported
MCM-41: An efficient solid acid catalyst for the green synthesis of xanthene-
dione derivatives, Journal of Molecular Catalysis 311 (2009) 36–45.
[26] BrukerSMART, SAINT-Plus and SADABS, Bruker Axs Inc., Madison, Wisconcin,
USA, 1998.
Acknowledgement
[27] G.M. Sheldrick,
112–122.
A short history of SHELX, Acta Crystallography A64 (2008)
This research did not receive any specific grant from funding
agencies in the public, commercial, or Not-for-profit sectors.
[28] M. Nardelli, Ring asymmetry parameters from out-of-plane atomic displace-
ments, Acta Crystallography C 39 (1983) 1141.
[29] L. Farrugia, ORTEP-3 for Windows - a version of ORTEP-III with a Graphical
User Interface (GUI), Journal of Applied Crystallography 30 (1997) 565.
[30] K. Brandenburg and H. Putz, Crystal Impact GbR, Bonn, Germany 2005.
[31] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheese-
man, G. Scalmani, V. Barone, G.A. Petersson, H. Nakatsuji, X. Li, M. Caricato,
A.V. Marenich, J. Bloino, B.G. Janesko, R. Gomperts, B. Mennucci, H.P. Hratchian,
J.V. Ortiz, A.F. Izmaylov, Sonnenberg, J.L. Williams, F. Ding, F. Lipparini, F. Egidi,
J. Goings, B. Peng, A. Petrone, T. Henderson, D. Ranasinghe, V.G. Zakrzewski,
J. Gao, N. Rega, G. Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota, R. Fukuda,
J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven,
K. Throssell Jr, J.A. Montgomery, J.E. Peralta, F. Ogliaro, M.J. Bearpark, J.J. Heyd,
E.N. Brothers, K.N. Kudin, V.N. Staroverov, T.A. Keith, R. Kobayashi, J. Nor-
mand, K. Raghavachari, A.P. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi,
J.M. Millam, M. Klene, C. Adamo, R. Cammi, J.W. Ochterski, R.L. Martin, K. Mo-
rokuma, O. Farkas, J.B. Foresman, D.J. Fox, Gaussian 16, Revision B.01, Gaussian,
Inc., Wallingford CT, 2016.
Reference
[1] S. Hatakeyama, N. Ochi, H. Numata, S. Takano, A new route to substituted
3-methoxycarbonyldihydropyrans; enantioselective synthesis of (–)-methyl
elenolate, Chemical. Communication 17 (1988) 1202–1204.
[2] Y.M.
Shchekotikhin,
T.G.
Nikolaeva,
Transformations
of
sym-octahydroxanthene-1,8-diones and 1,8-dioxo-sym-octahydroxanthylium
salts in recyclization under the influence of amines, Chemistry of Heterocyclic.
Compounds 42 (2006) 28–33.
[3] J. Venu Madhav, B. Suresh, Kuarm Rajitha, Dipyridine cobalt chloride: a novel
and efficient catalyst for the synthesis of 14-aryl 14H-dibenzo [a.j] xanthenes
under solvent-free conditions, Arkivoc 2 (2008) 204–209.
[4] K.Farahnaz Behbahani, Mastooreh Valliallahi, Synthesis of 14-aryl-14H-dibenzo
•
[a,j]xanthenes using CuSO4 5H2O as a green and reusable catalyst, Arabian
Journal of Chemistry 10 (2013) S1686–S1689.
[32] T.A. Dennington, J.M. Keith, Millam, GaussView, Version 6, Semichem Inc.,
Shawnee Mission, KS, 2016.
[5] R.M. Ion, D. Frackowiak, A. Planner, K. Wiktorowicz, The Incorporation of Vari-
ous Porphyrins into Blood Cells measured via Flow Cytometry, Absorption and
Emission Spectroscopy, Acta Biochimica Polonica 45 (1998) 833–845.
[6] J.P. Poupelin, G. Saint, R. Lacroix, Synthesis and Anti-inflammatory Proper-
ties of Bis(2-Hydroxy, 1-Naphthyl) Methane Derivatives, European Journal of
Medicinal Chemistry 13 (1978) 67–71.
[33] A.D. Becke, Density
– Functional Thermochemistry.I. The effect of the
exchange- only gradient correction, Journal Chemical Physics 96 (1992)
2155–2160.
[34] A.D. Becke, Density – Functional Thermochemistry .III. The role of exact ex-
change, Journal Chemical Physics 98 (1993) 5648–5652.
[7] A. Banerjee, A.K. Mukherjee, Chemical aspects of santalin as
stain, Journal of Stain Technology 56 (1981) 83–86.
a histological
[35] W.Yang C.Lee, R.G. Parr, Development of the colle-salvetti correlation-energy
formula into a functional of the electron density, Physical. Reviews. B 37 (1988)
785–789.
[8] A. Banerjee, A.K. Mukherjee, Biotech. Histochem. 56 (1981) 83.
[9] C.G. Knight, T. Stephens, Xanthene-dye-labelled phosphatidylethanolamines as
probes of interfacial pH. Studies in phospholipid vesicles, Biochemical Journal
258 (1989) 683–687.
[36] T. Koopmans, About the assignment of wave functions and eigenvalues to the
individual electrons of an atom, Physica 1 (1934) 104–113.
[37] M.J. Turner, J.J. McKinnon, S.K. Wolff, D.J. Grimwood, P.R. Spackman, D. Jayati-
laka, M.A. Spackman, Crystal Explorer, 17, The University of Western, 2017.
[38] M.A. Spackman, McKinnon, Fingerprinting intermolecular interactions in
molecular crystals, Crystal Engineering Communication 4 (2002) 378–392.
[39] M.A. Spackman, D. Jayatilaka, Hirshfeld surface analysis, Crystal Engineering
Communication 11 (2009) 19–32.
[10] M. Ahmad, T.A. King, K.K. Do, B.H. Cha, J. Lee, Performance and photostability
of xanthene and pyrromethene laser dyes in sol-gel phases, Journal of Physics
D: Applied Physics 35 (2002) 3265–3269.
[11] B. Maleki, A. Davoodi, M.V. Azghandi, M. Baghayeri, E. Akbarzadeh, H. Veisi,
S.S. Ashrafi, M. Raeia, Facile synthesis and investigation of 1, 8-dioxooctahy-
droxanthene derivatives as corrosion inhibitors for mild steel in hydrochloric
acid solution, New Journal of Chemistry 40 (2016) 1278–1286.
[40] J.J. McKinnon, M.A. Spackman, A.S. Mitchell, Novel tools for visualizing and ex-
ploring intermolecular interactions in molecular crystals, Acta Crystallography.
B 60 (2004) 627–668.
12

R. Shashi, N.S. Begum and A.K. Panday
Journal of Molecular Structure 1228 (2021) 129794
[41] A. Ilangovan, S. Muralidharan, P. Sakthivel, S. Malayappasamy, S. Karuppusamy,
M.P. Kaushik, A highly efficient green synthesis of 1, 8-dioxo-octahydroxan-
thenes, Chemistry Central Journal 5 (2011) 81.
[44] J.J. McKinnon, D. Jayatilaka, M.A. Spackman, Towards quantitative analysis of
intermolecular interactions with hirshfeld surfaces, Chemical Communication
37 (2007) 3814–3816.
[42] A. Javid, M.M. Heravi, F.F. Bamoharram, One-Pot synthesis of 1,8-Dioxo-oc-
tahydroxanthenes utilizing silica-supported preyssler nano particles as novel
and efficient reusable heterogeneous acidic catalyst, E-, Journal of Chemistry 8
(2011) 910–916.
[43] P. Iniyavan, S. Sarveswari, V. Vijayakumar, Microwave-assisted clean synthesis
of xanthenes and chromenes in [bmim][PF6] and their antioxidant studies, Re-
search on chemical intermediates 41 (10) (2015) 7413–7426.
[45] J. Aihara, Weighted HOMO-LUMO energy separation as an index of kinetic sta-
bility for fullerenes, Theoretical Chemical Accounts 102 (1999) 134–138.
[46] P.K. Bayannavar, M.S. Sannaikar, S.M. Kumar, S.R. Inamdar, S.K.J. Shaikh,
A.R. Nesaragi, R.R. Kamble, Synthesis, X-ray characterization, DFT
studies and hirshfeld surface analysis of new organic single
crystal:
2-(4-Methoxyphenyl)-4-{2
’-(1H-tetrazol-5-yl)biphenyl-4-yl
methyl}-2,4-dihydro-3H-1,2,4- triazol-3-one (MTBT), Journal of Molecular
Structure 1179 (2019) 809–819.
13