Green synthesis of tetraketones: crystal structure, DFT studies and Hirshfeld surface analysis of 2,2′-((3,4-dimethoxyphenyl) methylene) bis(3-hydroxy-5,5-dimethylcyclohex2-enone)

Article abstract of DOI:10.1080/15421406.2020.1829308

The present work deals with a practically efficient protocol designed for the synthesis of tetraketones using ultrasound in the presence of boric acid as the catalyst. One of the tetraketone, (3a) was confirmed by crystallographic studies. The molecules i

Full text of DOI:10.1080/15421406.2020.1829308

Molecular Crystals and Liquid Crystals
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gmcl20
Green synthesis of tetraketones: crystal structure,
DFT studies and Hirshfeld surface analysis of
2,2′-((3,4-dimethoxyphenyl) methylene) bis(3-
hydroxy-5,5-dimethylcyclohex2-enone)
R. Shashi, Noor Shahina Begum & Anoop Kumar Panday
To cite this article: R. Shashi, Noor Shahina Begum & Anoop Kumar Panday (2020) Green
synthesis of tetraketones: crystal structure, DFT studies and Hirshfeld surface analysis of 2,2′-((3,4-
dimethoxyphenyl) methylene) bis(3-hydroxy-5,5-dimethylcyclohex2-enone), Molecular Crystals and
Liquid Crystals, 709:1, 81-97, DOI: 10.1080/15421406.2020.1829308
To link to this article: https://doi.org/10.1080/15421406.2020.1829308
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MOLECULAR CRYSTALS AND LIQUID CRYSTALS
2020, VOL. 709, NO. 1, 81–97
https://doi.org/10.1080/15421406.2020.1829308
Green synthesis of tetraketones: crystal structure,
DFT studies and Hirshfeld surface analysis
of 2,20-((3,4-dimethoxyphenyl) methylene)
bis(3-hydroxy-5,5-dimethylcyclohex2-enone)
R. Shashia, Noor Shahina Beguma, and Anoop Kumar Pandayb
b
aDepartment of Studies in Chemistry, Bangalore University, Bangalore, Karnataka, India; Department
of Chemistry, Indian Institute of Technology Patna, Bihta, Bihar, India
KEYWORDS
ABSTRACT
Boric acid; crystal structure;
tetraketones; theoretical
studies; ultrasound
The present work deals with a practically efficient protocol designed
for the synthesis of tetraketones using ultrasound in the presence of
boric acid as the catalyst. One of the tetraketone, (3a) was confirmed
by crystallographic studies. The molecules in crystal lattice are held
together by weak intermolecular C–HꢀꢀꢀO, C–Hꢀꢀꢀp and intramolecular
O–HꢀꢀꢀO interactions. Hirshfeld surface analysis was carried out for
the graphical visualization, while, the 2D fingerprint plots provide
percentage contribution of each individual atom-to-atom interac-
tions. Finally, to determine molecular electrical transport properties,
we studied the energy difference between highest occupied, HOMO,
and lowest unoccupied, LUMO orbitals.
1. Introduction
In recent years, development of environmentally friendly, benign, cost effective and
clean synthetic procedures has become the most desired goal in the field of organic syn-
thesis. Organic reactions carried out by green method such as ultrasound employing
green solvents are more convenient and environmental friendly compared to traditional
methods. Therefore it has attracted much attention, especially from the viewpoints of
green chemistry [1]. Green chemistry approaches can lower energy costs, reduce chem-
ical wastage and lesser byproduct formation. The possibility of carrying out organic
reactions under green solvents can improve their ecological value [2]. Reactions carried
out in aqueous media are environmentally safe, devoid of carcinogenic effects, have sim-
ple work up, and are also especially suited for industry [3]. Thus, there is a need for the
development of organic reactions in aqueous medium.
Tetraketones are important precursors extensively used in the synthesis of acridine-
diones and for the synthesis of various heterocyclic compounds [4]. Tetraketones show
significant lipoxygenase inhibitor activity and strong anti-oxidant potential [5]. They
exhibit broad spectrum of therapeutic and biological properties [6–8]. Synthesis and
CONTACT Noor Shahina Begum
noorsb05@gmail.com;noorsb@bub.ernet.in
Department of Studies in Chemistry,
Bangalore University, Bangalore 560 056, Karnataka, India.
Supplemental data for this article is available online at https://doi.org/10.1080/15421406.2020.1829308.
ß 2020 Taylor & Francis Group, LLC

82
R. SHASHI ET AL.
biological application of tetraketone derivatives have received great interest due to their
structural similarity to those of biologically important compounds, such as NADH and
NADPH [9] and similar properties to those of 1,4-dihydropyridines.
Ultrasonic technique reduces the reaction duration, improves the yield and involves easier
work-up procedures than conventional methods [10]. Ultrasound works by the phenomenon
of cavitation. Collapse of these cavities creates drastic conditions inside the medium for an
extremely short time and temperatures of 2000–5000 K [10,11]. These cavitation-induced
effects can cause physical, chemical, and biological transformations more effectively.
The Clasien condensation and Michael addition of aldehydes with active methylene
compounds in the presence of acidic or alkaline catalysts are widely used as important
versatile precursors for the synthesis of tetraketones [12]. Because of their great practical
importance, several methods have been proposed, employing different catalysts and pro-
moters, some of them are NaOH [13], KOH [14], piperidine [15], proline [16], and
cetyltrimethyl ammonium bromide (CTMAB) [17]. Furthermore, catalyst-free reactions
in pure water [18], in solid state, and in melts have also been reported [19].
Unfortunately, most of the reported protocols are, although efficient, suffer from serious
drawbacks, such as high reaction temperature, longer reaction time, low yields, excess use
of reagents as well as toxic or expensive catalysts. As a result, we have developed a method-
ology to syntheses tetraketones which is efficient, green and easily adaptable.
Boric acid in recent years, has acquired a special attention for its catalytic activity in
organic syntheses due to its advantages such as excellent solubility in water, uncompli-
cated handling, inexpensiveness and eco-friendly nature. Therefore, this spurred our
interest to investigate the application of boric acid as a catalyst.
Owing to its numerous significance in methodology and the structure, we herein
report an ultrasound promoted simple, neat and efficient method for the syntheses of
tetraketone derivatives.
2. Experimental
2.1. Materials and methods
Ultrasonication was performed using SIDILU, Indian make sonic bath working at a
constant frequency of 35 kHz and an output power of 70 W at 28 ꢁC (maintained by cir-
culating water). The fine chemicals and solvents were purchased from Sigma-Aldrich,
Merck and Spectrochem, Bangalore. Melting points were determined in open capillaries
using Guna melting point apparatus and are uncorrected. The reactions and purity of
1
the products were monitored by Merck F-254 pre-coated TLC silica gel plates. H NMR
and 13C NMR were obtained on a Bruker AMX 400 spectrometer using CDCl3 with tet-
ramethylsilane as internal standard. IR spectra were recorded on Shimadzu FT-IR 8400S
and the values are reported in wave number (cmꢂ1).
2.2. General synthetic procedure for syntheses of tetraketones
A mixture of aldehyde (1 mmol), dimedone (2 mmol), and catalytic amount of boric
acid was treated with a 1:1 mixture of ethanol–water and placed in a sonic bath and
sonicated at 27 ꢁC until the reaction was completed to yield tetraketones (3a–j) as

MOLECULAR CRYSTALS AND LIQUID CRYSTALS
83
Scheme 1. Syntheses of tetraketones using boric acid in ultrasound condition.
shown in Scheme 1. All the reactions were monitored by thin-layer chromatography
(TLC) and after completion of the reaction, the mixture was cooled to room tempera-
ture and filtered. The precipitate obtained was washed with water.
2.3. Physical measurement
2-((2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)(3,4-dimethoxyphenyl)methyl)-5,5-
dimethylcyclohexane-1,3-dione (3a): C25H32O6, molecular weight: 428.51, yield: 80%,
m.p. 200 ꢁC, IR (KBr t cmꢂ1): 3298(OH), 1702(C ¼ O), 1596(C ¼ C). 1H NMR
(400 MHz, CDCl3) d 1.01 (6H, CH3, s), 1.12 (6H, CH3, s), 2.32–2.50 (8H, CH2, m),
3.79 (6H, OCH3, s), 5.51 (1H, CH, s), 7.19 (1H, J 8.5, Ph-H, d), 11.94 (2H, OH, s).
2-((2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)(4-methoxyphenyl)methyl)-5,5-
dimethylcyclohexane-1,3-dione (3c): C24H30O5 molecular weight: 398.20, yield: 88%, m.p.
1
197–200 ꢁC, IR (KBr t cmꢂ1): 3350.33(OH), 1601.26(C ¼ O), 1533.26(C ¼ C). H NMR
(400 MHz, CDCl3) d 1.12 (6H, CH3, s), 1.25 (6H, CH3, s), 2.51–2.29 (8H, CH2, m), 3.75
(3H, OCH3, S), 5.53 (1H, CH, s), 6.75–6.66 (m, 2H), 7.19 (t, J¼ 8.0 Hz, 1H), 11.57 (1H,
OH, s), 11.96 (1H, OH, s), ppm; 13C NMR (75MHz, CDCl3) d 190.3, 189.3, 159.5, 139.8,
129.0, 119.2, 115.6, 112.9, 111.1, 55.0, 47.1, 46.4, 32.8, 31.4, 29.6, 27.3.
3. Investigation techniques
3.1. X-ray single crystal structure analysis
Crystal of compound 3a was mounted on a Bruker Smart CCD Area Detector System
and the intensity data was collected using MoKa (0.7103 Å) radiation in x–u scan
mode. The data were reduced using SAINT-Plus [20]. The structure was solved by dir-
ect methods and refined on F2 using SHELX-97 [21] software package. All the non-
hydrogen atoms were refined anisotropically. As the hydrogen atoms 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 mean plane calculations were done using the program PARST [22].
Diagrams were generated using ORTEP-3 [23] and DIAMOND [24].
3.2. Computational details
Compound 3a is theoretically explored in detail for the comparative investigation with
experimentally obtained results of X-ray diffraction. All calculations were performed by

84
R. SHASHI ET AL.
Table 1. Optimization of solvent for the syntheses of tetraketones derivatives in ultra-
sound conditions.
Entry
Solvent
CH3CN
CHCl3
CH2Cl2
Water
Time (min)
Yield (%)
1.
2.
3.
4.
5.
6.
120
110
90
85
75
76
76
85
70
80
95
C2H5OH
C2H5OH– H2O
80
Gaussian 16 software package [25] and were visualized using Gauss View six without
any constraints on the geometry [26]. Density Functional Theory (DFT) calculations
using B3LYP method proposed by Becke [27,28]. Geometry optimizations were per-
formed using 6-311 þ G (d,p) basis set [29,30]. The structure was optimized without
any constraints. DFT optimized structure was confirmed to be minima on potential
energy surface (PES) by performing harmonic vibration frequency analysis (no imagin-
ary frequency found). No symmetry constraints were applied and only the default con-
vergence criteria were used during the geometric optimizations. The frontier molecular
orbital energies were calculated using 6-311 þ G (d,p) basis set. In addition to this,
molecular electrostatic potential map (MEP) was obtained from the output of B3LYP/6-
311 þ G (d,p) basis set.
4. Results and discussion
In continuation of our studies to synthesize pharmaceutically important tetraketones,
green procedures were employed. Herein, we wish to report the synthesis of tetrake-
tones in the presence of boric acid under ultrasound irradiation Scheme 1. Initially, a
sample reaction was carried out using benzaldehyde (1 mmol), dimedone (2 mmol), and
boric acid as a suitable catalyst in the presence of ethanol–water mixture as solvent for
the synthesis of 3b. The results are summarized in Table 2. It can easily be seen that
the condensation of a series of aldehydes with dimedone leads to the formation of tetra-
ketones (3a–j) in good yields under ultrasound irradiation (35 kHz) in the presence of a
Bronsted acid such as boric acid and a mixture of ethanol–water as solvent when com-
pared to other solvent systems as seen in the Table 1. As shown in Table 2, various aro-
matic aldehydes carrying either electron-releasing or electron-withdrawing substituents
can be obtained in high yields. It is more appealing to know the remarkable stability of
a variety of functional groups such as hydroxyl, nitro, and other substituents.
The methodology involves ultrasound in aqueous – ethanol medium. All the products
were formed in less than an hour. The formation of tetraketones (3a–j) from dimedone
and aromatic aldehyde in the presence of boric acid can be explained by a plausible
mechanism presented in Fig. 1. Initially activation of substituted benzaldehyde (1) takes
place with boric acid followed by attack of enol form of dimedone (2) to give an inter-
mediate (3) by loss of water molecule through Clasien-condensation mechanism. Finally
the second molecule of dimedone undergoes Micheal addition with intermediate three
furnishing the products 3a–j.

MOLECULAR CRYSTALS AND LIQUID CRYSTALS
85
Table 2. Isolated yields and time duration for formation of tetraketones 3a–3j.
Melting point (ꢁC)
Compound no.
R/substituent
Yield (%)
80
Time (min)
45
(literature value) [Ref. no.]
3a
200–202
3b
82
30
202–204 (194–195) [35]
3c
88
42
198–200 (197–200) [35]
3d
79
34
192–194 (197–198) [35]
3e
90
40
185–187 (187–189) [35]
(continued)

86
R. SHASHI ET AL.
Table 2. Continued.
Melting point (ꢁC)
Compound no.
R/substituent
Yield (%)
89
Time (min)
40
(literature value) [Ref. no.]
3f
171–173 (175–177) [35]
3g
89
35
190–192 (188–190) [35]
3h
86
43
195–197 (195–196) [36]
3i
90
45
201–203 (205–206) [36]
3j
84
40
187–189 (194–195) [29]

MOLECULAR CRYSTALS AND LIQUID CRYSTALS
87
Figure 1. Plausible mechanism for the formation of tetraketones with boric acid 3a–j.
4.1. Crystallographic studies
Appropriate crystals of compound 3a were obtained from slow evaporation method
using ethylacetate as solvent at room temperature and subjected to single crystal X-ray
diffraction analysis. A good quality single crystal was mounted along its largest dimen-
sion and used for data collection. Crystallographic data and other structure refinement
parameters of the compound 3a are given in Table 3. Weak interaction parameters in
compound 3a is given in Table 4. The ORTEP view of the molecules 3a with atomic
labeling (thermal ellipsoids drawn at 50% probability) is shown in Fig. 2. Figure 3 of
compound 3a shows the packing of the molecules.
In the compound 3a the C1/C2/C3/C4/C5/C6 cyclohexenone ring adopts half chair
conformation in which C1 and C4 are deviated by 0.0691(2) and 0.6310(2). Similarly
the C10/C11/C12/C13/C14/C15 cyclohexenone ring adopts boat conformation, in which
C10 and C13 are deviated by 0.1397(2) and 0.6587(2). Both C4 and C13 atoms carry
two methyl groups, lying above the respective mean plane.

88
R. SHASHI ET AL.
Table 3. Crystal data and refinement parameters for the compound 3a.
Compound name
3a
CCDC No.
CCDC-1874715
Chemical formula
Formula weight
T [k]
Wavelength [Å]
Crystal system
Space group
C25H32sO6
428.50
100(2) K
0.71073 Å
Triclinic
P-1
a [Å]
b [Å]
9.0127(9) Å
9.6897(10) Å
13.9770(13) Å
88.978(3)ꢁ
80.974(3)ꢁ
65.934(3)ꢁ
1099.27(19) A3
2, 1.301 mg/m3
0.092 mm–1
464
c [Å]
a [ꢁ]
b
c
Volume
Z, Density
Absorption coefficient
F(000)
Crystal size
0.14 ꢃ 0.17 ꢃ 0.15 mm
Theta range for data collection
Limiting indices
Reflections collected/unique
Completeness to theta
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2sigma(I)]
R indices (all data)
2.51–25.00ꢁ
–10 ꢄ h ꢄ 10, ꢂ11 ꢄ k ꢄ 11, ꢂ16 ꢄ l ꢄ 16
13461/3882 [R(int) ¼ 0.0779]
99.9%
0.9864 and 0.9855
Full-matrix least-squares on F2
3882/0/288
0.930
R1 ¼ 0.0580, wR2 ¼ 0.1005
R1 ¼ 0.1185, wR2 ¼ 0.1128
Table 4. Non-bonded interactions and possible hydrogen bonds (Å) for compound 3a (D, donor; A,
acceptor; H, hydrogen).
D–H…
A
D–H
H…
A
D…
A
D–H…
A
O2–H2… O1
0.840
0.840
0.980
0.980
0.980
0.990
0.9990
1.762
1.853
2.581
2.69
2.760
2.625
2.699
2.570
2.678
3.493
3.370
3.536
3.589
3.433
160.91
167.36
154.91
136
152.08
164.66
131.19
O3–H3… O4
C16–H16B… O5(i)
C8–H8B;;;Cg(ii)
C7–H7A;;;O4(iii)
C5–H5A;;;O6(iv)
C12–H12A;;;O1(v)
Symmetry codes: (i) -x þ 1, -y, -z; (ii) -x, -y, -z; (iii) -x þ 2, -y þ 1, -z; (iv) x þ 1, þy - 1, þz; (v) -x þ 2,-y þ 1,-z þ 1.
The 3,4-dimethoxy phenyl ring is almost perpendicular to the cyclohexenone rings
(C1/C2/C3/C4/C5/C6) and (C10/C11/C12/C13/C14/C15) making a dihedral angle of
74.19(8)˚ and 70.08(5)˚ respectively. The molecules in the crystal lattice are held
together by pair of weak intramolecular O–H … O hydrogen bonds forming parallel
layers to the, ab planes, forming inversion dimers. C–HꢀꢀꢀO and C–Hꢀꢀꢀk intermolecular
interactions are also observed. The hydroxyl and carbonyl oxygen atoms face each other
and are oriented to allow the formation of the two intramolecular O–H … O hydrogen
bonds which are typical of tetraketones due to their close proximity.
The atom O1 present in compound 3a accepts proton from two different donors, O2
and C12 generating bifurcated bonds along ‘c’ axis. The crystal structure is further stabi-
lized by C8–H8B … Cg interaction (Cg is the centroid of aryl ring C21/C22/C23/C18/
ꢀ
C19/C20) with a distance of 2.759 Å.

MOLECULAR CRYSTALS AND LIQUID CRYSTALS
89
Figure 2. ORTEP view of compound 3a.
4.2. Theoretical studies
4.2.1. Hirshfeld surface analysis
In order to study the intermolecular interactions in compound 3a, the Hirshfeld surface
(HS) analysis and related 2D finger plots were calculated using Crystal Explorer 17 [31]
by submitting the crystallographic information file (cif) of compound 3a. Surface fea-
tures which are characteristic of different types of intermolecular interactions can be
identified and these features can be visualized by color coding distances from the sur-
face to the nearest atom exterior (de plots) or interior (di plots) to the surface [32–34].
The dnorm mapped on the Hirshfeld surfaces were generated with color scale in between
ꢂ0.1489 au (blue) to 1.3286 au (red) respectively. The 2D fingerprint plots were dis-
played in the range of 0.4–2.6 Ð view with the de and di distance scales displayed on
the graph axis. Further the shape index mapped Hirshfeld were also used to visualize
different types of interactions. The intermolecular interactions in compound 3a are
visualized by mapping the Hirshfeld surface with different properties like de, dnorm
,
curvedness mapped, fragment patch mapped, and shape index [37] in Fig. 4.
In the Hirshfeld surface with the dnorm white color surface indicate the contacts with
the distances equal to the sum of the van der Waals radii and the red and blue color
indicate the distances shorter and longer than the van der Waals radii respectively.
All the 2D fingerprint plots of the compound 3a are shown in Fig. 5. It clearly indicates
that, in this molecule intermolecular interactions contributed by C···H, O···H, O···O, H···H,
and C···O, the maximum contribution are given by H···H (59.7%) and O···H (26.4%)

90
R. SHASHI ET AL.
Figure 3. Packing of the compound 3a showing intramolecular O–HꢀꢀꢀO (a) and intermolecular
C–HꢀꢀꢀO (b, c) and C–H···k (d) interactions.

MOLECULAR CRYSTALS AND LIQUID CRYSTALS
91
Figure 4. dnorm mapped, curvedness mapped, fragment patch mapped and shape index mapped on
Hirshfeld surface respectively of the compound 3a.
Figure 5. Finger print plots of compound 3a.
Table 5. Percentage of Hirshfeld finger print of the compound 3a.
C···H
O···H
O···O
H···H
C···O
12.7%
26.4%
0.7%
59.7%
0.5%
Table 6. Comparison of SCXRD and DFT bond lengths [Å] of compound 3a.
Distance (Å)
Distance (Å)
Atoms
SCXRD
DFT
Atoms
SCXRD
DFT
O(1)–C(2)
1.247(3)
1.334(3)
1.247(3)
1.371(3)
1.423(3)
1.364(3)
1.434(3)
1.524(3)
1.452(3)
1.514(3)
1.378(3)
1.403(3)
1.538(3)
1.371(3)
1.409(3)
1.506(3)
1.525(3)
1.384(3)
1.492(3)
1.533(3)
1.496(3)
1.390(3)
1.24095
1.32103
1.24493
1.36217
1.41887
1.36247
1.41801
1.53187
1.44926
1.53010
1.38724
1.40630
1.54007
1.38729
1.41528
1.51990
1.53888
1.38916
1.50433
1.54178
1.50585
1.40079
C(15)–C(14)
C(12)–C(13)
1.506(3)
1.526(3)
1.51762
1.53940
O(2)–C(11)
O(4)–C(15)
O(5)–C(21)
O(5)–C(25)
O(6)–C(20)
O(6)–C(24)
C(1)–C(9)
C(10)–C(15)
C(10)–C(9)
C(18)–C(23)
C(18)–C(19)
C(18)–C(9)
C(21)–C(22)
C(21)–C(20)
C(3)–C(2)
C(4)–C(8)
C(4)–C(7)
C(14)–C(13)
C(13)–C(17)
1.523(3)
1.530(3)
1.525(3)
1.524(3)
1.53783
1.54103
1.53747
1.53749
C(3)–C(4)
C(19)–C(20)
C(6)–C(5)
C(13)–C(16)
C(11)–C(12)
C(22)–C(23)

92
R. SHASHI ET AL.
Table 7. Comparison of SCXRD and DFT bond angles [ꢁ] for compound 3a.
Angle (ꢁ)
Angle (ꢁ)
Atoms
SCXRD
DFT
Atoms
SCXRD
DFT
C(21)–O(5)–C(25)
C(6)–C(1)–C(2)
C(2)–C(1)–C(9)
C(11)–C(10)–C(9)
C(23)–C(18)–C(19)
C(19)–C(18)–C(9)
C(10)–C(9)–C(18)
C(1)–C(6)–C(5)
C(11)–C(12)–C(13)
C(3)–C(4)–C(5)
C(19)–C(20)–C(21)
O(5)–C(21)–C(20)
C(2)–C(3)–C(4)
C(20)–C(19)–C(18)
O(6)–C(20)–C(19)
O(6)–C(20)–C(21)
O(3)–C(6)–C(1)
115.28(19)
117.9(2)
120.7(2)
126.4(2)
117.7(2)
117.4(2)
115.2(2)
123.9(2)
113.3(2)
118.09262
118.15600
120.41526
125.89985
117.74304
119.28036
115.97611
119.67244
114.95060
107.62114
119.67244
116.09156
115.85794
121.85186
124.80402
115.52350
124.47231
111.69220
111.74197
120.95014
120.19692
122.13907
115.06007
119.99405
120.22762
109.57553
109.57553
110.44630
121.90257
117.79941
109.47983
108.79083
110.87814
107.30129
110.45560
118.60774
C(20)–O(6)–C(24)
C(6)–C(1)–C(9)
117.23(19)
121.3(2)
117.1(2)
116.3(2)
124.6(2)
115.28(19)
113.5(2)
123.5(2)
109.5(2)
118.52770
118.52770
118.04433
115.93086
122.57076
113.03982
114.74335
124.93294
110.77985
C(11)–C(10)–C(15)
C(15)–C(10)–C(9)
C(23)–C(18)–C(9)
C(10)–C(9)–C(1)
C(1)–C(9)–C(18)
C(10)–C(11)–C(12)
C(3)–C(4)–C(7)
106.8(2)
119.6(2)
115.6(2)
114.1(2)
121.4(2)
125.1(2)
121.6(2)
115.3(2)
123.8(2)
112.2(2)
112.2(2)
120.6(2)
O(3)–C(6)–C(5)
O(2)–C(11)–C(12)
C(21)–C(22)–C(23)
C(18)–C(23)–C(22)
O(1)–C(2)–C(1)
C(15)–C(14)–C(13)
C(1)–C(2)–C(3)
C(10)–C(15)–C(14)
C(8)–C(4)–C(5)
C(8)–C(4)–C(7)
122.3(2)
113.9(2)
119.7(2)
119.9(2)
109.8(2)
109.2(2)
111.4(2)
121.4(2)
C(5)–C(4)–C(7)
O(4)–C(15)–C(10)
O(4)–C(15)–C(14)
C(17)–C(13)–C(12)
C(17)–C(13)–C(16)
C(12)–C(13)–C(16)
C(14)–C(13)–C(12)
C(14)–C(13)–C(16)
C(22)–C(21)–C(20)
118.7(2)
109.8(2)
108.4(2)
111.0(2)
106.6(2)
110.5(2)
119.1(2)
followed by C···H (12.7%), O···O (0.7%) and C···O (0.5%). The contribution of different
atoms are listed in Table 5. The higher amount of H···H interaction in this compound
shows that van der Waals interaction also plays a major role in the crystal packing.
4.2.2. Molecular geometry optimizations
The structure of the compound 3a was optimized by DFT calculations using B3LYP
method with 6-311 þ G (d,p) basis set. The comparison of selected optimized geometrical
parameters such as bond length, bond angles and torsion angles, with those parameters
obtained from XRD studies are listed in Tables 6–8. The minor deviations observed
between the theoretically calculated and experimentally determined values can be accounted
for the differences in molecular environment between the crystalline phase and gas phase.
4.2.3. Frontier molecular orbital analysis
HOMO; highest occupied molecular orbital and LUMO; lowest unoccupied molecular
orbital, are known as FMOs. The energy difference between the HOMO and LUMO

MOLECULAR CRYSTALS AND LIQUID CRYSTALS
93
Table 8. Comparison of SCXRD and DFT calculated torsion angles [ꢁ] for compound 3a.
Angle (ꢁ)
Angle (ꢁ)
Atoms
SCXRD
DFT
Atoms
SCXRD
DFT
C(11)–C(10)–C(9)–C(1)
C(11)–C(10)–C(9)–C(18)
C(6)–C(1)–C(9)–C(10)
C(6)–C(1)–C(9)–C(18)
C(23)–C(18)–C(9)–C(10)
C(23)–C(18)–C(9)–C(1)
C(25)–O(5)–C(21)–C(22)
C(23)–C(18)–C(19)–C(20)
C(24)–O(6)–C(20)–C(19)
C(18)–C(19)–C(20)–O(6)
O(5)–C(21)–C(20)–O(6)
O(5)–C(21)–C(20)–C(19)
C(2)–C(1)–C(6)–O(3)
–80.5(3)
54.7(3)
–93.1(3)
130.9(2)
0.4(3)
136.4(2)
–6.8(3)
–0.9(4)
ꢂ2.6(3)
–179.9(2)
0.3(3)
–179.7(2)
–169.5(2)
10.1(4)
–83.64411
51.84836
–91.85651
132.08233
16.63517
151.37607
–0.49784
–1.06594
0.37774
–179.87648
0.49604
–179.56763
–170.26664
8.15180
C(15)–C(10)–C(9)–C(1)
C(15)–C(10)–C(9)–C(18)
C(2)–C(1)–C(9)–C(10)
C(2)–C(1)–C(9)–C(18)
C(19)–C(18)–C(9)–C(10)
C(19)–C(18)–C(9)–C(1)
C(25)–O(5)–C(21)–C(20)
C(9)–C(18)–C(19)–C(20)
C(24)–O(6)–C(20)–C(21)
C(18)–C(19)–C(20)–C(21)
C(22)–C(21)–C(20)–O(6)
C(22)–C(21)–C(20)–C(19)
C(9)–C(1)–C(6)–O(3)
94.0(3)
–130.8(2)
82.7(3)
–53.3(3)
173.4(2)
–50.5(3)
172.6(2)
–174.4(2)
177.4(2)
0.2(4)
92.19095
–132.31658
83.42884
–52.63231
–170.84614
–36.10525
179.62237
–173.94423
–179.68963
0.19349
179.8(2)
–0.3(4)
6.4(4)
–179.39221
0.54412
5.12208
C(2)–C(1)–C(6)–C(5)
C(9)–C(1)–C(6)–C(5)
–174.0(2)
–176.45948
C(15)–C(10)–C(11)–O(2)
C(15)–C(10)–C(11)–C(12)
O(5)–C(21)–C(22)–C(23)
C(19)–C(18)–C(23)–C(22)
C(21)–C(22)–C(23)–C(18)
C(9)–C(1)–C(2)–O(1)
C(9)–C(1)–C(2)–C(3)
C(4)–C(3)–C(2)–O(1)
C(9)–C(10)–C(15)–O(4)
C(9)–C(10)–C(15)–C(14)
C(10)–C(11)–C(12)–C(13)
C(1)–C(6)–C(5)–C(4)
C(2)–C(3)–C(4)–C(5)
C(6)–C(5)–C(4)–C(8)
C(6)–C(5)–C(4)–C(7)
C(10)–C(15)–C(14)–C(13)
C(15)–C(14)–C(13)–C(12)
C(11)–C(12)–C(13)–C(17)
–168.0(2)
13.5(3)
–179.6(2)
1.6(4)
–1.7(4)
–3.0(3)
–179.2(2)
153.5(2)
ꢂ9.9(3)
172.6(2)
20.4(3)
17.0(4)
52.9(3)
–165.8(2)
73.1(3)
–22.4(3)
52.5(3)
–171.3(2)
–169.96904
9.50414
179.72859
1.21676
C(9)–C(10)–C(11)–O(2)
C(9)–C(10)–C(11)–C(12)
C(20)–C(21)–C(22)–C(23)
C(9)–C(18)–C(23)–C(22)
C(6)–C(1)–C(2)–O(1)
C(6)–C(1)–C(2)–C(3)
C(4)–C(3)–C(2)–C(1)
C(11)–C(10)–C(15)–O(4)
C(11)–C(10)–C(15)–C(14)
O(2)–C(11)–C(12)–C(13)
O(3)–C(6)–C(5)–C(4)
C(2)–C(3)–C(4)–C(8)
C(2)–C(3)–C(4)–C(7)
6.5(4)
–172.0(2)
1.0(4)
174.6(2)
172.9(2)
–3.3(3)
–30.1(3)
165.2(2)
–12.4(3)
–158.3(2)
–163.5(2)
172.0(2)
–67.9(3)
–46.5(3)
160.0(2)
171.8(2)
–68.2(3)
–51.6(3)
5.78689
–174.73993
–0.39438
173.84431
169.13508
–7.69876
–21.82891
169.52553
–7.35556
–160.75417
–160.46891
166.20677
–73.79303
–46.32319
159.12895
167.94693
–71.99587
–47.01427
–0.50811
–6.29445
176.87170
161.20159
ꢂ6.65239
176.46652
19.71080
20.93426
47.04114
–165.58396
74.72029
–23.86419
48.97339
–166.27222
C(6)–C(5)–C(4)–C(3)
O(4)–C(15)–C(14)–C(13)
C(15)–C(14)–C(13)–C(17)
C(15)–C(14)–C(13)–C(16)
C(11)–C(12)–C(13)–C(14)
orbitals is called the energy gap (Eg). The calculated HOMO and LUMO energies for
compound 3a in Fig. 6 is found to be ꢂ5.571 eV and ꢂ1.624 eV respectively and energy
gap (Eg ¼ ELUMO-EHOMO) is 3.947 eV. This large energy gap value in the compound 3a
indicates high stability and low reactivity [38]. The importance of the FMOs is in deter-
mining the electronic properties, optical properties, and chemical reactivity’s. The
energy of the highest occupied molecular orbital (HOMO) is related to the ionization
potential, while the energy of the lowest unoccupied molecular orbital (LUMO) is
related to the electronic affinity.
The global reactivity parameters related to frontier molecular orbital energies are
chemical hardness (g ¼ 1.973 eV), electronegativity (v ¼ 3.597 eV), electronic chemical
potential (m ¼ ꢂ3.597 eV), global electrophilicity index (x ¼ 3.278 eV). Table 9 which
were calculated from HOMO–LUMO energy values [39].
4.2.4. Atomic charge analysis
The Mulliken charge distributions of the compound 3a have been calculated using 6-
311 þ G (d,p) level shown in Fig. 7. In compound 3a, the magnitude of the carbon
Mulliken charges, is found to be either positive or negative ranging from ꢂ1.188 to

94
R. SHASHI ET AL.
Figure 6. HOMO–LUMO orbitals of title compound 3a.
Table 9. The energy values of global reactivity descriptors.
Parameter
Value (eV)
ELUMO
EHOMO
DE
–1.624
–5.571
3.947
1.973
3.597
–3.597
0.253
3.278
Chemical hardness (g)
Electronegativity (v)
Chemical potential (m)
Chemical softness (s)
Global electrophilicity index (x)
Figure 7. Mulliken charges plot of title compound 3a.
1.521. The highest positive charge is over carbon (C1 ¼ 1.521) atom. Among all the pro-
tons which carry positive charge the highest positively charged hydrogen atoms are H2
(0.389) and H3 (0.35), while all oxygen atoms have a negative charge.

MOLECULAR CRYSTALS AND LIQUID CRYSTALS
95
Figure 8. MEP surface of title compound 3a.
4.2.5. Molecular electrostatic potential analysis
The molecular electrostatic potential (MEP) analysis can be regarded as a powerful tool
for identifying the possible interaction sites around a molecule. One of the most inter-
esting features of quantum chemistry is the ability to explain the reactivity of com-
pounds under investigation. It determines the reactivity of a chemical system by
predicting electrophilic as well as nucleophilic sites in target molecules. The computed
MEP using 6-311 þ G (d,p) level of DFT is shown in Fig. 8. The MEP surface allows us
to visualize the various regions of a molecule. The charge distribution helps to deter-
mine the molecules interaction and the nature of the chemical bond. The positive area
of the MEP is a nucleophilic site, while the negative region is associated with an electro-
philic site. Figure 8 shows the negative charges are more and they are concentrated
around the oxygen atom. The color code of the map is in the range between
ꢂ5.939 ꢃ 10ꢂ2 a.u. (deepest red) and 5.939 ꢃ 10ꢂ2 a.u. (deepest blue) in the maps, the
most negative region on the MEP surface of the title compound is associated with the
lone-pairs of the oxygen atom.
5. Conclusion
In conclusion, application of ultrasound results in significant benefits such as intensified
processing, low level of waste generation, inherently safe operation, material and energy
saving as well as increase in productivity, all of which confirm the greener processing
based on the use of ultrasound.
We have developed an environmentally benign and green method using less harmful
solvents such as ethanol–water system in the presence of Bronsted acid catalyst such as

96
R. SHASHI ET AL.
boric acid for the syntheses of tetraketones. Further studies in our laboratory are under-
way to develop multicomponent reactions in milder reaction medium.
The single crystal X-ray studies revealed that the title compound is stabilized by a
pair of intramolecular O–H···O and intermolecular C–H···O and C–H···k interactions.
As for the calculated DFT, by B3LYP method it shows good agreement with the experi-
mental results. The three-dimensional dnorm and 2D fingerprint plots from Hirshfeld
surfaces analysis were extensively studied to understand the intermolecular interactions.
The Hirshfeld surface analysis disclosed that maximum interactions, contributed for
crystal packing was from H···H (59.7%) and O···H (26.4%). The correlation coefficient
between the bond lengths and bond angles of experimental and theoretical values
showed that the structure obtained by the single crystal XRD is well agreeable with the
optimized structure. The MEP plots revealed the possible reactions sites of the molecule.
The Mulliken atomic charges were also analyzed for the nucleophilic and electrophilic
regions on the molecular surface. The HOMO–LUMO large energy gap value of the
compound indicates high stability and low reactivity suggesting a good stability of the
compound 3a.
6. Supplementary data
Supplementary crystallographic data for this article in CIF format are available at the
Electronic Supplementary Publication from Cambridge Crystallographic Data Center
(CCDC 1874715). http://www.ccdc.cam.ac.uk/conts/retrieving.html, from the Cambridge
Crystallographic Data Center, 12 Union Rood, Cambridge CB2 1EZ, UK (Fax: (inter-
national): þ44 1223/336 033; email: deposit @ ccdc.cam.ac.uk).
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