Synthesis, spectroscopic and photophysical studies of xanthene derivatives

Article abstract of DOI:10.1016/j.molstruc.2017.08.054

We report on the experimental, crystal structure and computational investigation of a new class of xanthenes obtained by the reaction of salicylaldehyde and its derivatives with, 5,5-Dimethylcyclohexane-1,3-dione (Dimedone). The synthesized xanthenes were

Full text of DOI:10.1016/j.molstruc.2017.08.054

Accepted Manuscript
Synthesis, spectroscopic and photophysical studies of xanthene derivatives
Mohammad Ramezani Taghartapeh, Nader Noroozi Pesyan, Hamid Rashidnejad,
Hamid Reza Khavasi, Alireza Soltani
PII:
S0022-2860(17)31120-1
10.1016/j.molstruc.2017.08.054
MOLSTR 24192
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 19 June 2017
Revised Date: 10 August 2017
Accepted Date: 15 August 2017
Please cite this article as: M.R. Taghartapeh, N. Noroozi Pesyan, H. Rashidnejad, H.R. Khavasi,
A. Soltani, Synthesis, spectroscopic and photophysical studies of xanthene derivatives, Journal of
Molecular Structure (2017), doi: 10.1016/j.molstruc.2017.08.054.
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Synthesis, spectroscopic and photophysical studies of xanthene derivatives
Mohammad Ramezani Taghartapeh*, a, Nader Noroozi Pesyana, Hamid Rashidnejada, Hamid
Reza Khavasib Alireza Soltanic
,
aDepartment of Organic Chemistry, Faculty of Chemistry, Urmia university, 57159, Urmia, Iran
bDepartment of Chemistry, Faculty of Science, Shahid Beheshti University, Tehran, Iran
cJoints, Bones and Connective Tissue Research Center, Golestan University of Medical Science,
Gorgan, Iran
Abstract
We report on the experimental, crystal structure and computational investigation of a new
class of xanthenes obtained by the reaction of salicylaldehyde and its derivatives with, 5,5-
Dimethylcyclohexane-1,3-dione (Dimedone). The synthesized xanthenes were characterized
1
13
by state-of-the-art techniques, such as IR, Raman, H and C NMR, Single Crystal X-ray
crystallography, UV-Vis and photophysical measurements. The structure, ground-
andexcited-state properties of one xanthene derivative was investigated using Density
Functional Theory (DFT) and Time-Dependent DFT (TD-DFT) calculations with and without
solvent (ethanol). The optimized geometries and predicted IR frequencies were in good
agreement with experimental data. Hirshfeld surface analyses were carried out to gain insight
on the close-contact interactions of the crystal, where hydrogen showed the highest
contribution (66.1%). The synthetic route proposed in this work does not use any catalysts
and leads to high yields (75-85 %), therefore being an interesting alternative to synthesize
xanthene derivatives.
Keywords: Xanthene, Hirshfeld surface analysis, spectroscopic analysis, DFT and TD-DFT
calculations, Non-liner optical parameters.
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* Corresponding author. E-mails: mramezanitaghartapeh@swin.edu.au
Introduction
The chemistry of xanthene derivatives with their countless applications has attracted the
attention of synthetic pharmacologists, laser physicists, and chemists [1]. Many applications
in biology and photochemistry have been reported utilizing these compounds as anti-viral,
anti-inflammatory and anti-bacterial agent [2-6]. These molecules have also been used as
dyes in laser technology and as pH-sensitive fluorescent materials for bio-imaging [7, 8].
Moreover, they exhibit potential cytotoxic activity against colon cancer cell lines, especially
for Colon-205 and Colon-502713 [9]. Some xanthene-based drugs were efficiently
intercalated into the DNA and also have been reported to act as radical scavengers [10, 11].
Xanthene dyes can be synthesized by means of a catalytic reaction using (PhCO2)2,
Friedel–Crafts reaction, application of DABCO or using salicylaldehyde [12-15] among
others [16]. In view of the very large variety of xanthene derivatives and their even larger
range of applications, the development of novel synthetic protocols to obtain different
xanthene molecules is very important. The understanding of alternative reactions in the
synthesis of xanthenes and its derivatives is therefore a key factor, if one wishes to generate
novel drugs, dyes and materials with promising properties.
Theoretical methods can help elucidate synthetic mechanisms of xanthene, as well as to
characterize the final product by means of predicting several ground- and excited-state
properties. The use of such methods is often seen in different fields of science, such as
chemistry, physics, and biology [17-21] In particular, Density Functional Theory (DFT) and
Time-Dependent DFT (TD-DFT) have been broadly employed in many experimental-
theoretical investigations [22-24], which is due to the simplicity and predictive power of
these methods when compared with computationally more demanding ab initio methods.
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Among the many different DFT methods developed so far, the hybrid B3LYP functional has
been extensively used to treat organic molecules[23,24], which is due to its low
computational cost when compared with other functionals, associated to a high accuracy in
the prediction of general properties of those molecules.
In this work we present an alternative synthetic method to obtain new xanthene derivatives
and make their characterization by means of combining several experimental techniques and
further DFT and TD-DFT calculations over 9-(2-hydroxy-4,4- dimethyl-6-oxocyclohex-1-
enyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (6). It has a potential application for
use as a selective and orally active antagonist for neuropeptide YY5 receptor (xanthene class
of Y5 antagonists) [3]. It was previously synthesized using alkali [25], acetic acid/H2O [26],
and water catalyzed by triethylbenzylammonium chloride [27] We show that our alternative
synthetic protocol not only gives comparable yields as those reported in the literature for 6,
but also is considerably cheaper and does not use any catalysts.
Methodologies
Synthesis
The condensation reaction of 5, 5-dimethylcyclohexane-1, 3-dione (dimedone, compound
1) with salicylaldehyde (2) and its derivatives (3-5) in EtOH under reflux afforded the
xanthene class of derivatives (6-9, See Scheme 1 and 2) based on the mechanism represented
as scheme 1. Dimedone (10 mmol, 1.4 g) and salicylaldehyde (5mmol, 0.6 g) were dissolved
in 20 ml ethanol, stirred in a round bottom flask for 24 h, precipitated, filtered off, then
washed with cold ethanol to yield a white solid (6). A similar procedure was used to
synthesize 7-9. All reactions were monitored by TLC with silica gel-coated plates
(AcOEt:AcOH / 80:20 / v:v). Compounds 1 and 2 and all solvents used in this work were
purchased from Merck and Aldrich, without further purification. Single crystal of 6 was
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obtained as a colorless crystal by slow evaporation of the solvent (EtOH) at room
temperature.
<Scheme 1>
<Scheme 2>
Characterization
Products 6-9 were characterized using state-of-the-art techniques. Melting points were
measured with a digital melting point apparatus (Electrothermal), (Urmia University, Urmia,
Iran). IR spectra were recorded in the region 4000-400 cm-1 on a NEXUS 670 FT-IR
spectrometer (resolution: 0.1 cm-1) by preparing KBr pellets (Urmia University, Urmia,
Iran).Raman spectrum was recorded in the region 100-4400 (cm-1) using Teksan
Spectroscopy (Model: Takram P50C0R10) that has the resolution of 0.6 cm-1. The 1H and
13C NMR spectra were recorded on a high-resolution Bruker 300 FT-NMR at 300 and 75
MHz, respectively (Urmia University, Urmia, Iran). 1H and 13C-NMR spectra were obtained
in CDCl3 using TMS as internal standard and elemental analysis (CHN), just for 6, was also
performed (Urmia University, Urmia, Iran). The UV-visible spectrum of 6 was recorded on a
T80 UV-Vis spectrometer (PG Instruments Ltd) in the region 190-1100 nm with the
resolution of 0.2 nm and the photoluminescence spectra of 6 at room temperature and
different concentrations were carried out using a Jasco 6500 spectrophotometer with a xenon
lamp and 1 nm of resolution bothat (Urmia University, Urmia, Iran). Single crystal X-ray
diffraction of 6 was also collected on STOE IPDS-II or IPDS-2T (Shahid Beheshti
University, Tehran, Iran) with the detector resolution of 0.15 mm pixels mm-1.
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Theoretical calculations
The geometry of 6 was optimized using DFT calculations with the hybrid (B3LYP) and
non-hybrid (PBE0) functionals and 6-311++G** basis set using the Gaussian 09 program
package [28]. Solvent effects were included in the calculations via the PCM model, where the
dielectric constant of ethanol (ε = 24.852) was used. Vibrational frequencies were also
calculated at PBE1PBE and B3LYP functionals and 6-311++G** basis set to check the
reliability of the optimized structure, as well as to help assign experimental IR transitions
with further studies of all possible vibrational assignments using VEDA software [29]. TD-
DFT was then employed to predict the excited states of 6 using the previously optimized
ground state geometry with the same functional and basis set. The oscillator strengths and
intensities of each transition were used to build a theoretical UV-Vis spectrum, where
Gaussian functions with fixed widths were centered at each transition wavelength.
Hirshfeld surface analysis
In order to discuss the packing of 6 inside the molecular crystal, as well as to discuss the
close contacts between atoms in the single crystal in solid, a Hirshfeld analysis was carried
out. A detailed analysis was carried out to study various intermolecular interactions of H···H,
H···O/O···H, C···H/H···O and O···O types of contacts present in the crystal structures of 6,
using the program Crystal Explorer 3.0 [30].
Results and Discussion
Appearance, melting point value and interpretation of FT-IR, H-NMR and C-NMR of 6-9.
9-(2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-
xanthen- 1-one(6): White solid; m.p. 191-193 °C (decomps.); FT-IR (KBr) 3180.8 (OH),
2953.9, 2927.6, 2869.3 (CH aliph.), 1642.3 (C=O), 1593.4 (C=C ar.), 1374.1 (CH3), 1232.2
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(C-O) cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.01 (s, 6H), 1.04 (s, 3H), 1.14 (s, 3H), 1.97 (d,
2H, J=4.8 Hz), 2.33-2.59(m, 6H), 4.68 (s, 1H), 7.05-7.18 (m, 4H), 10.48 (bs, 1H); 13C NMR
(CDCl3, 75 MHz) δ 200.9,196.5, 170.7, 169.1, 151.1, 128.0, 127.5, 124.6, 124.3, 118.3,
115.7, 111.1, 50.6, 49.9, 43.2, 41.6,32.3, 30.9, 29.9, 29.2, 27.8, 27.2, 26.5. (Supplementary
Information section, Figure S1-6).
Elemental analysis of (6): C23H26O4, Calc.: C 75.5%, H 7.1%. Found: 77.2%, H 7.2%.
12-(2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-9,9-dimethyl-9,10-dihydro-
8Hbenzo[a]xanthen-11(12H)-one (7): White solid; m.p. 243 °C (decomps.); FT-IR (KBr)
3173.4(OH), 2944.9 (CH aliph.), 1642.5 (C=O), 1591.6 (C=C ar.), 1374.7 (CH3), 1236.0 (C-
O) cm-1;1H NMR (CDCl3, 300 MHz) δ 0.72 (s, 3H), 0.94 (s, 3H), 1.06 (s, 3H), 1.16 (s, 3H),
1.82 (d, 1H,J= 15.3 Hz), 1.95 (d, 1H, J= 15.3 Hz), 2.39 (m, 4H), 2.55 (d, 1H, J= 17.4 Hz),
2.67 (d, 1H, J=17.4 Hz), 5.26 (s, 1H), 7.25-7.70 (m, 6H), 10.67 (bs, 1H); 13C NMR (CDCl3,
75 MHz) δ 201.0,196.8, 170.2, 169.0, 148.9, 131.3, 131.0, 128.5, 128.4, 126.7, 124.6, 122.9,
117.7, 116.6, 116.1,111.1, 50.7, 50.0, 43.2, 41.4, 32.4, 30.6, 29.8, 29.3, 27.1, 26.4, 25.4.
9-(2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-5-methoxy-3,3-dimethyl-2,3,4,9-
tetrahydro-1H-xanthen-1-one (8): White solid; White solid; m.p. 202-205 °C (decomps.); FT-
IR (KBr) 3202(OH), 3029 (CH ar.), 2954 (CH aliph.), 1643 (C=O), 1586 (C=C ar.), 1376
(CH3), 1229 (C-O)cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.01 (s, 6H), 1.04 (s, 3H), 1.13 (s,
3H), 1.98 (d, 2H, J=4.8Hz), 2.34-2.72 (m, 6H), 3.90 (s, 3H), 4.68 (s, 1H), 6.60 (d, 1H, J= 7.5
Hz), 6.77 (d, 1H, J= 8.1Hz), 6.95 (t, 1H, J= 7.8 Hz), 10.43 (bs, 1H); 13C NMR (CDCl3, 75
MHz) δ 200.9, 196.5, 170.6,168.8, 147.1, 140.7, 125.2, 124.2, 119.8, 118.2, 110.9, 110.4,
56.1, 50.6, 50.0, 43.2, 41.6, 32.3,30.9, 29.9, 29.1, 27.8, 27.2, 26.5.(Supplementary
Information section, Figure S7-11).
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9-(2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-7-nitro-2,3,4,9-
tetrahydro-1H-xanthen-1-one (9): White solid; m.p. 206-208 °C; FT-IR (KBr) 3184 (OH),
2958 (CH aliph.),1652 (C=O), 1597 (C=C ar.), 1376 (CH3), 1239 (C-O) cm-1; 1H NMR
(CDCl3, 300 MHz) δ 0.96(s, 6H), 1.03 (s, 3H), 1.15 (s, 3H), 1.98 (m, 2H), 2.36-2.65 (m, 6H),
4.70 (s, 1H), 7.12 (d, 1H, J=9.0 Hz), 7.93 (d, 1H, J= 2.1 Hz), 8.05 (dd, 1H, J= 8.7, 2.4 Hz),
10.34 (bs, 1H); 13C NMR(CDCl3, 75 MHz) δ 200.8, 196.9, 172.0, 167.8, 155.4, 144.2,
125.9, 123.8, 123.6, 117.6, 116.4,110.9, 50.5, 49.9, 43.2, 41.2, 32.3, 31.2, 29.6, 29.2, 27.8,
27.0, 26.7. (Supplementary Information section, Figure S12-16).
Compounds 6-9 were obtained with high yields: 85 %, 75 %, 82%, and 84 %, respectively.
These results are very good, especially if one remembers that no catalysts were used in the
reactions. The compound 6 was chosen as a representative compound to be further
investigated with X-Ray measurements and Hirshfeld surface analysis, as well as with
theoretical DFT and TD-DFT calculations.
Crystal structure, theoretical intermolecular H-bonds and theoretical pKa analysis of 6.
The crystallographic structure of 6 was elucidated using X-ray diffraction of the single
crystal (Supplementary Information section, Figure S20). This compound crystallizes in the
monoclinic space group P21/c. The relevant data is represented as a summary in Table 1.
Boat and half-chair conformations were observed for the main pyran and outer cyclohexene
of the xanthene moiety, respectively. As reported in the literature, there is other cyclohexane
with skew boat conformation that is bonded to the central pyran [27].
<Table1>
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The crystal structure of 6 indicates three kinds of H-bonds. Intermolecular H-bonds were
observed between H2B and O3 (Figure 1 right), where donor–acceptor distances d (O···O)
were 2.664 Å. This value falls within the range 2.5 ≤ d (O···O) ≤ 2.7 Å, which is typical for
mediumstrong H-bonds [31-34].Values for d (O···O) of two other H-bonds indicate these
bonds are weak, as shown in (Table 2).
<Figure 1>
Further study of the H-bonds strength in 6 and consequent comparisons with those of
other carboxylic and flavones acids and methyl 2,4-dimethoxysalicilate reported by Wallet et
al [35-36]and Dabbagh et al[37], have permitted us to elucidate the pKa of 6 when the
experimental quantification of pKa is difficult. The estimated pKa value for intermolecular
H-bond of 6 is ≈ 5.6 which is in good agreement with the experimental results for xanthene
class of compounds (Fluorescein= 6.10± 0.04 and 2-(3, 6- dihydroxy-9-acridinyl) benzoic
acid–azafluorescein= 6.23± .0.9) reported by Batistela and coworkers [38].Moreover, based
on the correlation between H-bond strength (EHB) and d (O···O) [37, 39], one can find EHB
≈
21 kcal.mol-1 for 6 (Supplementary Information section, Figure S21).
<Table 2>
Hirshfeld surface analysis (HSA) of 6
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HSA was carried out to understand and better describe the crystal packing of 6, where
close contacts can be easily highlighted. Two-dimensional fingerprint plots were used to
quantify and visualize the intermolecular interactions involved in this packing, which are
shown in Figure2. The Hirshfeld surfaces were constructed using different representations,
such as de, di,dnorm [40],shape index and curvedness. In the Hirshfeld surface diagrams, the
close contacts whose distances are equal to the sum of the van der Waals radius of both close-
contact atoms are white colored, while the close contacts whose distances are shorter than
and longer than that sum are represented by red and blue, respectively. Any part of every
fingerprint represents a close contact, which is highlighted in Blue (Figures2i-m). The total
percentile contributions of close contacts such as H···H, O···H/H···O, C···H/H···C, and
O···O were 66.1%, 18.5%, 14.2% and 1.2%, respectively. As one can see, the intermolecular
H···H contact share predominant in the packing of 6.
<Figure 2>
Geometry optimization of 6
The geometry of 6was optimized using DFT calculations (Figure 3) indicate that there are
negligible changes within the bond length, bond angle, and torsion angle values obtained by
crystal structure and those calculated at B3LYP method. Comparative data of theoretical and
experimental geometrical parameters are presented in (See Supplementary Information
section, Table S1). The predicted bond lengths, bond angle and torsion angles. for 6 in both
vacuum and ethanol phases as solvent were in good agreement with the crystallographic
results revealing the reliability of the B3LYP and PBE0 methods for optimizing the geometry
of xanthene class of compounds, as already reported in several previous reports [18-21,41].
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There may be some differences and that are mainly due to the unimolecular gas phase
optimization for the former, where intermolecular interactions do not exist [40].
<Figure 3>
Experimental and calculated absorption and emission spectra of 6
The absorption and emission spectra of 6 in ethanol at room temperature are shown in
Figure 4.(Blue and red lines).This emission spectrum was also measured for different
concentrations (2.2×10-3 M, 1.1×10-3M, and 5.5×10-4 M) and did not show any changes in
shape whereas the intensity of the emission spectra increased upon the lowing of the
concentration of6. (Supplementary Information section, Figure S22). Both absorption and
emission occur mostly at the UV region and its molar absorptivity in ethanol at λmax (280 nm)
is 2×103 M-1 cm-1, which is low when compared with other xanthenes, while the λem has
emerged at 340 nm resulting in a Stokes shift (ꢀλ) of 60 nm as the consequences of no
symmetry and moderate value of dipole moment to the long axes of 6,the fluorescence band
moderately overlaps the absorption band (Figure 4) [42], makes it a promising candidate for
bio-imaging and bio-diagnostics applications[43].This value appreciably corresponds toꢀλ of
a xanthene dye reported by Yang et al [44].The theoretical absorption spectrum is in good
agreement with the experimental one, the deviation found being attributed to the implicit
solvent model (PCM) used instead of the computationally-demanding explicit model, as well
as to limitations on the basis set and functional used. The PBE0 functional gave considerably
better results than B3LYP for the excited states of 6 when compared with experimental
values (Figure5).
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<Figure 4>
<Figure 5>
For all ground-state properties we used B3LYP and PBE0 functionals, while the B3LYP
converges much faster than PBE0 and has similar accuracy. The compositions of the
electronic transitions in terms of molecular orbitals are shown in Table 3. The maximum
absorption occurs at 300 nm and corresponds to the π→π* electronic transition from the
highest-occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital
(LUMO), as well as from HOMO to LUMO+1 almost in all calculated cases.Concerning the
literaturefor the absorption of xanthene dyes, our results agree well with the λmax reported for
some xanthene dyes synthesized using aldehydes (dibenzo[b, d]furan-2-carbaldehyde,
dibenzo[b, d] thiophene-2-carbaldehyde and 9-methyl-9Hcarbazole-3-carbaldehyde) and
cyclic 1,3-dicarbonyls which were in the range of 285 nm to 302 nm obtained in three
different solvents (Chloroform, acetonitrile and tetrahydrofuran) [45].The second major peak
is observed between 309-325 for the studied states which mainly corresponds to H-1→L and
finally the third main peak of the studied states were observed in the range of 325-345 with
the π→π* electronic transition from H → L and an exception of H→ L+1 (38 %) as the major
contribution in PBE0 (Ethanol) model of transition state calculation. The main occurred
electronic transition can be attributed to n→π* transitionsdue to the possible conjugations of
lone pair of hydroxylandKetone functionalities with the βdouble bonds (C15=C17 and
C8=C9)and also the lone pair of O atom of pyran ring that has resonance with the electrons of
π bonds of benzene ring of 6. Moreover, Table 3 and 4 represent that the λmax at both B3LYP
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and PBE functionals reduced from vacuum to ethanol phase resulted in more stabilization of
n transition which consequently reduces the Egap of 6.
<Table 3>
Electronic properties of 6
The calculated electron density of the frontier molecular orbitals (FMOs) of 6 in vacuum
and ethanol calculated at B3LYP/6-311++G** functional is plotted in Figure 6 and their
energies are summarized in Table 4. The energies of HOMO and LUMO were determined to
be (-5.92 and -1.44 eV for vacuum phase) and (-5.80 and -1.28 eV for ethanol phase) with the
corresponding Egap of 4.48 and 4.52 eV, respectively. Moghanian et.al stated that the HOMO,
LUMO and Egap calculated for the synthesized xanthene were -5.57, -1.19 and 4.38 eV, which
appreciably confirm our calculated results [46]. Moreover, recently K. Anandhan et.al
reported a similar data for these items that were -5.52, -1.19 and 4.38 eV, respectively. Figure
6 clearly shows that the HOMO is delocalized over the aromatic moiety of the molecule and
has a large contribution from the oxygen atoms. Using the Koopmans’ theorem [47,48] and
calculated values of HOMO and LUMO, we determined quantum molecular descriptors of
chemical potential (ꢁ), global hardness (η), electrophilicity index (ω), and softness (S) in the
gas and solvent (ethanol) phases, respectively, whose values are shown in Table 4.
<Figure 6>
<Table 4>
The molecular orbitals calculated for 6 were used to make the Molecular Electrostatic
Potential (MEP) plot, from where regions of positive and negative potentials can be seen
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(Supplementary Information section, Figure S23). Mulliken atomic partial charges were also
calculated for 6 in vacuum and in ethanol (Supplementary Information section, Table S2).
Both results predict the most negative region of 6 to be located around the carbonyl group
while the outer ring of that compound, which bears the hydroxyl group, is related to a more
positive region. The Molecular Electrostatic Potential (MEP) map is a very practical three-
dimensional diagram which reveals features of the electronegativity and electropositivity of
molecular structures. MEP maps are a valuable tool in organic chemistry to predict the
behavior of complex molecules [47,48] The MEP plot of compound 6 is shown in Figure S4.
Blue and red zones represent positive and negative potentials, respectively. The increase of
negative electronic potential can be observed by the color changes, as blue (more positive)
<green<yellow<orange<red (more negative) [49-50]. As it is clear from the Figure S4, the C-
O and C-O-C groups represent the deep and soft red color zones, respectively, standing for
the negative potential nature of these areas. The central zone of ring A represents a slight
yellow color corresponding to a negligible negative potential. Other meaningful color zone is
observed over the ring D, where there is a blue color zone. The Mulliken partial charges for
all atoms of 6 obtained from DFT calculations in vacuum and in ethanol are reported in
Supplementary Information section, Table S2. As it is predicted, the O atoms have gained
negative charges as O4 (-0.198) > O3 (-0.123) > O2 (-0.108) > O1 (-0.073). Almost all C
atoms were negatively charged, except for C1, C6, C7, C8, and C16, which is due to having α
and β positions toward Oxygen-containing groups, and C11 and C19 because of a uniform
distribution of electrons in these atoms. Moreover, all of the H atoms have positive partial
charges as expected. Electron rich and electron poor position of compound 6 is appreciably
confirmed by the results of Milliken population analysis.
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Vibrational Analysis of 6
The vibrational frequencies of 6 was calculated using DFT at the B3LYP and PBE0
functionals and 6-311++G** basis set and then compared with those obtained experimentally
by FT-IR spectroscopy. Experimental and theoretical studies of 6 were provided in the Figure
7 and Table 5, respectively. In this investigation, the scaling factor employed from the
B3LYP and PBE functionals are with values in the range of 0.97-1.02 [51].
<Figure 7>
The heteroaromatic and aromatic hydrocarbon structures show the presence of C-H
stretching vibrations in the region 3000-3100 cm-1 by FT-IR spectrum [40, 45]. In this region,
the bands are not appreciably affected by the nature of the substituents. In the FT-IR
spectrum, the bands at 3100, 2954, and 2874 cm-1 are assigned to the C-H stretching and the
bands at 1440, 1376, 1311, 755, and 473 cm-1 are assigned to the C-H bending. The
theoretical vibrations assigned to aromatic C-H stretching appear in the region 3100-3016 cm-
1, which is in agreement with the corresponding experimental values of 3088-3016 cm-1
previously reported for this kind of vibration [52, 53]. While in case of our study, the C-H
vibration frequencies appear at 3079 and 3111 by B3LYP functional and 3219 and 3247 cm-1
by PBE functional. The C-H symmetry stretching was observed at 3085 cm-1 with predicted
bands at 3079 and 3111 cm-1 by B3LYP and PBE functionals, respectively. A medium C-H
stretching vibration was observed at 2954 cm-1 and it is almost well correlated with the
experimental value of 3016 cm-1. In Table 5, FT-IR spectrum displayed the presence of
aromatic ring (1643 cm-1) and aliphatic hydrogen’s (2980 cm-1), which is close to the
obtained results by Ghoran and co-workers [54]. C-H methyl bending vibrations were
observed at 1376 cm-1 and it coincides with the computed value at 1392 cm-1. A weak C-H
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in-plane bending vibration was observed at 1440 cm-1 and it exactly coincides with the
calculated at ≈1440 cm-1. With a medium intensity C-H bending vibrations was observed at
1312, 1257, 755 and 473 cm-1, which correlated well with the predicted values 1320, 1248,
768 (out of plane), and 408 cm-1, respectively. The experimental O-H vibrations have a much
lower frequency (3178 cm-1) when compared with the DFT ones (2746 and 2768 cm-1 at
B3LYP and PBE methods, respectively). This is due to hydrogen bonding involving the
hydroxyl groups taking place in the solid state, which is well-known to weaken O-H
stretching vibrations, therefore decreasing the corresponding frequency [55-58]. Since the
DFT calculations were done for one single molecule of 6 and without any explicit solvent
molecules, no hydrogen bonding involving O-H groups takes place, which means O-H
vibrations are stronger and have higher frequencies, as indeed observed. The ring C-C
stretching bonds available in benzene causes six C-C stretching vibrations. The observed
bands at 1589 and 1489 cm-1 in FT-IR are recognized as C=C double bond stretching
vibrations. In Table 5, the experimental spectrum shows a strong band at around 1643 cm-1 is
assigned to C-C stretching vibration which is comparable with the values of 1639 and 1652
cm-1 by B3LYP and PBE functionals, respectively [59]. The ring breathing mode is assigned
at 589 and 1489 cm-1 in FT-IR. The calculated value at 1632 and 1512 cm-1 is in good
agreement with experimental data. Moreover, the bands at 1704, 1697, 1673, 1643, 1535 are
related to the C=C stretching mode of ring C and D which these results are appreciably
supported by theoretical values for bands at B3LYP and PBE methods (see Table 5).
Generally, C-O bands are displayed in the region 1205-1050 cm-1. In the spectra of aliphatic
ether bonds, the most characteristic absorption is a strong band in the range of 1150-1085 cm-
1. Spectra of aryl alkyl ethers display an asymmetrical C-O-C stretching band at 1275-1200
cm-1 with symmetrical stretching near 1075-1020 cm-1. In title molecule, the C-O stretching
vibration is observed at 1200 and 1021 cm-1 and it exactly coincides with the calculated at
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1200 and 1016 cm-1. Moreover band at 1257 displays the C-O-C vibration of the xanthen ring
(ring B) which is in good agreement with the results obtained by B3LYP (1278 cm-1) and
PBE (1279 cm-1) methods. For more information of some selected modes calculated using
potential energy distribution at B3LYP and PBE methods please see the Table 5.
<Table 5>
Raman Spectroscopy study of 6
The Raman spectroscopy has been implemented to plot the Raman spectra of 6 at excitation
wavelength of 532 nm that is represented in Figure 8. The in-plane stretching and
deformation modes are represented by υ and δ. The band at 3435 cm-1 associates to the -OH
group of ring D. The weak and medium strong bands at 1264, 1377 cm-1 and strong band at
2893 assign to δ(C-CH3) vibrations and band at 1461 cm-1 represents the δ(CH2) and δ(CH3)
asymmetric vibrations. Bands with weak intensities at 959 and 1132 cm-1 assign to the
symmetric and asymmetric υ (C-O-C) vibrations and strong band at 1613 cm-1 relates to the
hetero ring (xanthene ring). The band at 1027 cm-1, and shoulder at 1508 cm-1 correspond to
the υ (C-C) aromatic ring chain vibrations.
<Figure 8>
Nonlinear Optical (NLO) analysis of 6
As the final stage of our calculations, to measure Dipole Moment (DM), the linear
polarizability (α) and the first hyperpolarizability (β) at the same DFT levels of theory as
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previously described, the corresponding values were inserted into the following equations
[60]:
Total Dipole Moment (Debye) = DMXdirection+DMY direction +DMZ directioneq.1
ꢅꢃ ꢅꢃ
ꢀꢁꢂꢁ =  ꢃ
ꢇꢇ eq.2
ꢄꢄ
ꢆꢆ
ꢈ
ꢍ
ꢎꢏ
ꢍ
ꢎꢏ
ꢍ
ꢎꢏ
ꢉꢊꢋꢊ = ꢌ βxxx + βxyy + βxzz + βyyy + βyzz + βyxx + βzzz + βzxx + βzyy eq.3
The result indicated that, the values of dipole moment, linear polarizability and first
hyperpolarizability were 2.626 (Debye), 22.754×10-24(esu) and 61.248×10-32 (esu) using
B3LYP method. Ahmed et al. have reported the value of 20.3×10-24for the polarizability of
9H- xanthene compound which is in well agreement with our result [61].
Conclusions
New xanthene derivatives were synthesized from the reaction of dimedone with
salicylaldehyde and its derivatives. Our alternative synthetic route is cheap, gives rise to high
yields (75-85 %) and does not use catalysts, making it very attractive. The synthesized
xanthenes were characterized by state-of-the-art techniques and a single crystal of 6 could be
grown and was analyzed by X-ray crystallography. Hirshfeld surface analysis revealed that
most of the close contact interactions in the crystal involved hydrogens, which had a very
high contribution (66.1%). The DFT calculations gave insight on the general properties of 6
and helped characterize that compound. The theoretical results also suggest that the
functional B3LYP may be only employed for xanthene dyes when ground-state properties are
envisaged, while PBE0 should be preferred when the prediction of excited-state properties is
pursued. Comparison of the experimentally obtained and theoretical predicted IR bands and
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UV-Vis absorption spectra were appreciably similar. The bands observed at Raman
spectroscopy study confirm the formation of 6 where the C-H, C-O-C, C-C and O-H bands
are clearly visible in the Raman spectrum.
Acknowledgments
The authors want to thank Urmia University for providing partial support of the work and
instrumental analysis facilities.
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Figure and Table Captions
Scheme 1. Proposed mechanism for the formation of 6-9.
Scheme 2.Schematc reactions for the formation of 6-9.
Figure 1. ORTEP diagram (left) and respective crystal packing showing intermolecular
oxygen-oxygen close contacts (right) of 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-
3,3,dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one.
Figure 2. (a-h): Views of the Hirshfeld surfaces mapped with dnorm, shape index and
curvedness viewed from front (a-d) and back (e-h) faces and 2D fingerprint plots for 6 with
different close contacts and their relative contributions (i-m) of 9-(2-hydroxy-4,4-dimethyl-6-
oxocyclohex-1-enyl)-3,3,dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one.
Figure 3. Optimized structure of 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-
3,3,dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one labeled according to the number of atoms
and the rings named as A, B, C and D.
Figure 4. Experimental absorption and experimental emission concentration at 2.7×10-4 M
and theoretical (TD-DFT, PBE0/6-31++G**) absorption spectra of 9-(2-hydroxy-4,4-
dimethyl-6-oxocyclohex-1-enyl)-3,3,dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one.
Figure 5.experimental (violet line) and theoretical PBE (black dashed line)/ B3LYP (pink
dashed line) UV-vis spectra of 6.
Figure 6. DFT electron densities of the frontier molecular orbitals of 9-(2-hydroxy-4,4-
dimethyl-6-oxocyclohex-1-enyl)-3,3,dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-
oneoptimized in vacuum represented over the density of states (DOS) plot in ethanol phase at
B3LYP and PBE0 methods and 6-311++G** basis sets.
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Figure 7.Normalized experimental (FT-IR) and calculated (B3LYP/6-31++G**) infrared
spectra of 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-3,3,dimethyl-2,3,4,9-
tetrahydro-1H-xanthen-1-one.
Figure 8. Raman Spectrum of 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-
3,3,dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one.
Table1. Crystal data for 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-3,3,dimethyl-
2,3,4,9-tetrahydro-1H-xanthen-1-one.
Table 2. Intermolecular H-bond distances (Å) and angles (degree) for 9-(2-hydroxy-4,4-
dimethyl-6-oxocyclohex-1-enyl)-3,3,dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one.
Table 3. TD-DFT energies (B3LYP and PBE0) and intensities of vertical excitations
calculated
for
9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-3,3,dimethyl-2,3,4,9-
tetrahydro-1H-xanthen-1-one and the corresponding composition in terms of one-electron
transitions between molecularorbitals (H = HOMO and L = LUMO).
Table 4. Frontier molecular orbitals and quantum molecular descriptors of 9-(2-hydroxy-4,4-
dimethyl-6-oxocyclohex-1-enyl)-3,3,dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-oneat
B3LYP and PBE0 methods.
Table 5.Selected vibrational assignments of 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-
enyl)-3,3,dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-oneby B3LYP and PBE methods.
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Scheme 1.
26

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Scheme 2.
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Figure 1.
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Figure 2.
29