Synthetic and theoretical investigation on nano-Au/TiO2 catalyzed hydrothiolation for construction of C─S bond: Experimental and DFT study

Article abstract of DOI:10.1002/poc.4040

In this article, we describe a new synthetic and theoretical approach for the construction of C─S bond in heterocyclic molecules undergoing nanogold catalytic hydrothiolation reaction. The experimental studies showed that the reaction proceeded via regioselective Michael-type anti-addition and gave the corresponding sulfur bridged 1,3,4-oxadiazole-propenone in excellent yield. The compounds were characterized by analytical and spectral techniques. A gas phase molecular modeling study of nanogold-catalyzed hydrothiolation of acetylenic ketone with 5-aryl-1,3,4-oxadiazol-2-thiol was carried out using density functional theory (DFT) calculations. It showed the adsorption of acetylenic ketone on nanogold and preferable coordination at the β carbon of the alkyne group. The charge calculations showed that on adsorption over nanogold, the alkyne group became more polar in nature. The frontier highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) analysis showed a possible overlap of molecular orbitals between thiol and acetylenic β carbon to give Z isomer. The experimental and theoretical validation of bond parameters was carried out. A possible mechanism of hydrothiolation reaction was proposed based on the analogy with the results of theoretical calculations and experimental evidence.

Full text of DOI:10.1002/poc.4040

Received: 27 June 2019
DOI: 10.1002/poc.4040
Revised: 4 October 2019
Accepted: 3 November 2019
R E S E A R C H A R T I C L E
Synthetic and theoretical investigation on nano‐Au/TiO2
catalyzed hydrothiolation for construction of C─S bond:
Experimental and DFT study
Vishwanath Turukarabettu1,2 | Balakrishna Kalluraya1
1 Department of Chemistry, Mangalore
Abstract
University, Karnataka, India
In this article, we describe a new synthetic and theoretical approach for
the construction of C─S bond in heterocyclic molecules undergoing nanogold
catalytic hydrothiolation reaction. The experimental studies showed that the
reaction proceeded via regioselective Michael‐type anti‐addition and gave
the corresponding sulfur bridged 1,3,4‐oxadiazole‐propenone in excellent
yield. The compounds were characterized by analytical and spectral tech-
niques. A gas phase molecular modeling study of nanogold‐catalyzed
hydrothiolation of acetylenic ketone with 5‐aryl‐1,3,4‐oxadiazol‐2‐thiol was
carried out using density functional theory (DFT) calculations. It showed
the adsorption of acetylenic ketone on nanogold and preferable coordination
at the β carbon of the alkyne group. The charge calculations showed that on
adsorption over nanogold, the alkyne group became more polar in nature.
The frontier highest occupied molecular orbital (HOMO) and lowest un-
occupied molecular orbital (LUMO) analysis showed a possible overlap of
molecular orbitals between thiol and acetylenic β carbon to give Z isomer.
The experimental and theoretical validation of bond parameters was
carried out. A possible mechanism of hydrothiolation reaction was proposed
based on the analogy with the results of theoretical calculations and experi-
mental evidence.
2 Department of Materials Science,
Mangalore University, Karnataka, India
Correspondence
Balakrishna Kalluraya, Department of
Chemistry, Mangalore University,
Mangalagangothri, Karnataka, India.
Email: bkalluraya@gmail.com
KEYWORDS
DFT studies, hydrothiolation, nanogold, nitrofuran, oxadiazole, titania
1 | INTRODUCTION
biologically active pharmacophores can be a prevalent
method to synthesize bioactive molecules in medicinal
Compounds with C─S bonds are widely distributed in
nature and in many drug molecules such as ranitidine,
thorazine, cimetidine, and 6‐mercaptopurine.[1–3] The
hydrothiolation of unsaturated bonds such as alkynes,
olefins, propenones, acetylenic ketones, and episulphide
is a prevalent synthetic route for C─S bond construc-
tion.[4–8] Further, hydrothiolation of an activated inter-
nal alkyne using heterocyclic thiol of which both are
chemistry. However, the conventional method of C─S
bond formation suffers from few disadvantages such as
low yield, harsh reaction conditions, prolonged reaction
time, and use of hazardous chemicals.
Although sulfur poisoning is a potential obstacle in
development of catalysts for C─S bond formation, several
homogeneous catalysts were reported for thiol click
chemistry, involving the nucleophilic attack of sulfur on
J Phys Org Chem. 2019;e4040.
wileyonlinelibrary.com/journal/poc
© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/poc.4040

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TURUKARABETTU AND KALLURAYA
terminal alkynes and unactivated alkenes. PdCl2(PhCN)2,
RhH (CO)(PPh3)3, Pt (PPh3)4, NiCl2(PPh3)2, Ni (acac)
2 | EXPERIMENTAL
,
[9,10] Pd (OAc)2,[11,12] and Wilkinson's complex[13–15] cat-
2.1 | Materials and methods
2
alysts were used for hydrothiolation of terminal alkynes
under different organic solvent systems. A series of palla-
dium catalysts, PtCl2, NiCl2, and CuCl2 were reported for
internal alkyne‐thiol addition. Pd (OAc)2 was used in the
treatment of 1‐alkynylphosphine which resulted in regio-
selective and stereoselective anti‐hydrothiolation.[16]
Lewis acid Ca (OSO2C4F9)2 catalyst under microwave
irradiation significantly reduced the reaction time.[17]
The first gold catalyzed intramolecular C─S bond forma-
tion of thio‐allene system was reported by Morita et al.[18]
Organogold complexes were used for hydrothiolation of
unactivated alkenes leading to anti‐Markovnikov addi-
tion.[4,19] However, the use of homogeneous catalysts
need a tedious preparative methods and work up proce-
dures in organic solvents which are usually hazardous.
Although the transition metal complex catalyzed
nucleophilic alkyl and benzene thiol addition to alkenes
and terminal alkyne has been studied extensively,
the reports on hydrothiolation of α,β‐unsaturated
ketones[20,21] are only few by conventional methods.
Recently many articles and reviews explored the cata-
lytic role of heterogeneous nanoparticles in organic
transformations.[22–25] High surface to volume ratio and
surface properties of nanomaterials have made them sus-
tainable alternatives to conventional materials in cataly-
sis, sensors, electronic devices, and drugs.[26,27]
Nanosized materials have emerged as core materials in
synthetic chemistry in view of process efficiency and
avoiding hazardous substances.[28–33] Silica nanoparticles
catalyzed addition of thiols to inactivated alkenes and
alkynes.[34] It is reported that gold nanoparticles are
highly active when they are supported on metal
oxides.[35] Gold on titania catalyzes the Claus reaction
and is 5 to 10 times faster than titania itself indicating
that gold can be sulfur tolerant.[25] To the best of our
knowledge, this is the first report of nanogold‐catalyzed
hydrothiolation of acetylenic ketone with 5‐aryl‐1,3,4‐
oxadiazol‐2‐thiol to synthesize Z‐3‐[5‐nitro (furan/thio-
phene)‐2‐yl]‐1‐phenyl‐3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐
ylthio)prop‐2‐en‐1‐one (Scheme 1). A molecular model-
ing study was proposed for the selective hydrothiolation
of acetylenic ketone with 5‐aryl‐1,3,4‐oxadiazole‐2‐thiol
based on the density functional theory (DFT) using
quantum espresso software.
All chemicals were purchased from commercial chemical
suppliers and used after purification. Ultraviolet visible
diffuse reflectance spectra (DRS) were recorded on
Shimadzu UV‐3101PC UV‐Vis‐NIR spectrophotometer
fitted with ISR 240A DRS integrating sphere. The
Fourier‐transform infrared (FT‐IR) spectra of samples
were recorded on Schimadzu FT‐IR‐157 spectrophotome-
ter. The crystal phase of catalyst was analyzed using
Rigaku powder X‐ray diffractometer (Cu Kα radiation, λ
= 1.5405 Å, 0.02 s−1). Particle size was imaged using
Carl‐Zeiss field emission scanning electron microscope
(FE‐SEM) attached with EDX Spectrometer (Oxford
instruments) and high‐resolution transmission electron
microscopy (HRTEM). The physisorption studies of tita-
nia and Au/TiO2 nanospheres were performed with
Quantachrome Autosorb‐1 physisorption analyzer. The
1H and 13C NMR spectra were recorded on an Agilent
VNMRS‐400 MHz NMR spectrometer. Mass spectrum
was recorded using Shimadzu 8030‐LCMS/MS mass spec-
trometer. The single crystal X‐ray diffraction data was
collected on a Bruker D8 Venture Photon 100 CMOS
instrument.
2.2 | Synthesis of nano‐Au/TiO2 catalyst
and hydrothiolation of acetylenic ketone
Porous TiO2 nanospheres were prepared as per the
solvothermal method reported in literature.[36] The
deposition‐precipitation technique was used to prepare
nano‐Au/TiO2 catalyst (Figures S1 and S2).[37] To a solu-
tion of 3‐[5‐nitro (furan/thiophene)‐2‐yl]‐1‐phenyl‐prop‐
2‐yn‐1‐one[38] (0.5 mmol) 2 in 20 mL of ethanol taken
in a round bottomed flask, 5‐phenyl‐1,3,4‐oxadiazole‐2‐
thiol[39,40] 1 (0.5 mmol), and nano‐Au/TiO2 catalyst (5
mg) were added. It was heated on a water bath at 80°C.
The hot solution was filtered to separate the catalyst.
The filtrate was then rota‐evaporated to remove excess
solvent and then cooled. The solid obtained was filtered,
dried, and recrystallized from DMF/ethanol mixture.
The progress of the hydrothiolation was monitored by
ascending thin‐layer chromatography on silica gel G‐Al
SCHEME 1 Nanogold‐catalyzed
hydrothiolation of acetylenic ketone

TURUKARABETTU AND KALLURAYA
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backed (Merck) and observed under UV light (mobile
phase, hexane:ethyl acetate, 3:1).
2.3 | DFT molecular modeling study
The computational molecular modeling calculations were
carried out in a Lenovo laptop with intel core i3 processor
4 GB RAM, using quantum espresso software package
v.5.1 based on DFT.[41,42] The structure of molecules
was obtained by relevant relax calculations using
PWrelax (plane wave relax) code of the quantum espresso
package with relevant pseudopotentials of elements
obtained from the quantum espresso website.[43] The
ibrav value was set to 12 for monoclinic primitive cell.
The ecutwfc value was set to 30 and ecutrho was 240 with
occupations smearing. Then the molecular energy calcu-
lation was carried out using PWscf (plane wave self‐
consistent field) code by fixing the coordinates of relaxed
structure of molecule. The structure was viewed by
Xcrysden visualization program.[44] The frontier highest
occupied molecular orbital (HOMO) and lowest unoccu-
pied molecular orbital (LUMO) calculation of the mole-
cules was carried out using pp.x code with isovalue
0.001 and viewed using Xcrysden visualization program.
The pdos calculation was carried out using projwfc.x code
to identify the partial charges.
FIGURE 1 UV‐visible spectra of nanoporous TiO2 and nano‐Au/
TiO2 with Tauc plots
37.90°, 47.93°, 53.91°, 54.85°, 62.62°, 68.99°, and 75.08°
corresponding to the (101), (004), (200), (105), (211),
(204), (116), and (215) planes of anatase phase of TiO2
(JCPDS file No. 894921). It indicated that TiO2 nano-
spheres exist in a single phase of anatase. For nano‐Au/
TiO2, a small peak was observed at 44.10° corresponding
to (200) plane of gold and the peak required at 38° (111)
might have been buried in 37.90° peak of TiO2 (JCPDS
file No. 040784). The least intensity of peak at 44.10° for
gold indicated that a very low concentration (1.9 wt%)
of gold nanoparticles was dispersed on TiO2 matrix. The
position of TiO2 peaks corresponding to anatase phase
was not shifted to any side for nano‐Au/TiO2 indicating
that the crystal phases of TiO2 nanospheres were unal-
tered by addition of gold nanoparticles; however, a small
3 | RESULTS AND DISCUSSION
3.1 | Characterization of nano‐Au/TiO2
3.1.1 | UV‐Vis DRS and FT‐IR analysis
The DRS of TiO2 nanospheres and nano‐Au/TiO2 are
plotted as corresponding Kubelka‐Munk function F (Rα)
values versus wavelength is shown in Figure 1. The
absorption band centered at 600‐nm range correspond
to the plasmon resonance confirms the presence of gold
nanoparticles in TiO2 matrix. The extrapolation of linear
portion of the Tauc plots (inset) gave the band gap energy
values of 3.04 eV for TiO2 and 3.05 eV for nano‐Au/TiO2,
which indicated that the adsorption of gold nanoparticles
on titania has not altered the band gap of TiO2 nano-
spheres. The IR spectra of TiO2 and nano‐Au/TiO2
showed a broad band appeared at 500 cm−1 due to Ti─O
stretching (Figure S3).
3.1.2 | Powder XRD analysis
The X‐ray diffraction (XRD) patterns (Figure 2) of TiO2
and nano‐Au/TiO2 showed peaks at 2θ values of 25.22°,
FIGURE 2 X‐ray diffraction (XRD) patterns of (A) nano‐TiO2
and (B) nano‐Au/TiO2

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TURUKARABETTU AND KALLURAYA
increase in full width at half maximum (FWHM) for (101)
plane) from 0.8470 (TiO2) to 0.8860 (Au/TiO2) indicated
the reduction in size of TiO2 nanospheres during the
addition of gold to TiO2 matrix.
The BJH pore size distribution curve showed a small
shift in pore width distribution of nano‐Au/TiO2 towards
lower value from that of TiO2 which indicated that the
gold nanoparticles were doped on the surface of TiO2
nanoparticles
3.1.3 | FE‐SEM, EDAX, and HRTEM
analysis
3.2 | Hydrothiolation reaction
The FE‐SEM image (Figure S4) of TiO2 nanoparticles
showed that the particles have average size of 90 nm. The
energy dispersive spectrum showed gold peaks which con-
firmed its presence in TiO2 matrix. The HRTEM image
(Figure 3) of nano‐Au/TiO2 revealed that the average par-
ticle size of gold was approximately 10 nm and deposited
on TiO2. The interplanar spacing (d‐spacing) values of
TiO2 and Au nanoparticles were 0.352 and 0.239 nm,
respectively, corresponding to the (101) plane of anatase
phase of TiO2 and (111) plane of nano‐Au/TiO2.
The reaction time, yield data, and solvent conditions of
nano‐Au/TiO2 catalyzed hydrothiolation reaction for
compound 3a are given in Table 1. It was found that
the hydrothiolation reaction proceeded via anti‐addition
and only Z isomer was obtained in all solvent conditions.
In ethanol, the reaction was completed in 30 minutes
under heating at 80°C open to air. In presence of nitrogen
gas atmosphere, the reaction was completed within 20
minutes of heating without change in yield and stereo-
chemistry of product. The reaction was also carried out
in water as a green approach to avoid hazardous organic
solvents like benzene. Gold nanoparticles are
alkynophillic in nature. Since acetylenic ketone would
preferably get adsorbed on gold nanoparticles, this fur-
nishes the hydrothiolation in water under catalyzed con-
ditions. However, it was observed that the progress of
reaction was not encouraging compared with ethanol as
solvent. Addition of small volume of THF or BuOH to
water increased the solubility of reactants, and yield was
improved.
Both recovered catalyst and fresh catalysts showed
identical IR absorption bands (Figure S3) indicating that
the catalyst was not poisoned during the reaction. The
UV‐Vis spectrum of synthesized compounds did not show
3.1.4 | Nitrogen adsorption‐desorption
studies
Figure 4 shows the nitrogen adsorption‐desorption iso-
therm of nano‐TiO2 and nano‐Au/TiO2 and their corre-
sponding Barrett‐Joyner‐Halenda (BJH) pore size
distribution curves (inset). It was observed that the curves
resemble a type IV isotherm, which is a typical character-
istic of mesoporous materials.[45] The BET‐specific sur-
face area, pore volume, and average pore width of nano‐
TiO2 were found to be 73.55 m2/g, 0.162 cm3/g, and
8.80 nm and for nano‐Au/TiO2 64.07 m2/g, 0.128 cm3/g,
and 6.1 nm, respectively.
t
FIGURE 3 (A) Transmission electron microscopy (TEM) image of nano‐Au/TiO2 and (B) high‐resolution transmission electron
microscopy (HRTEM) image of nano‐Au/TiO2 depicting the interplanar spacing

TURUKARABETTU AND KALLURAYA
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FIGURE 4 Physisorption isotherms of
porous TiO2 and Au/TiO2 nanospheres
plasmon resonance corresponding to gold nanoparticles,
which indicated that the products were devoid of nano‐
Au/TiO2 (Figure S5). It was observed that the reaction
time was reduced with increase in the amount of catalyst
in the reaction. The catalyst was washed with dichloro-
methane and reused for six successive cycles under nitro-
gen gas atmosphere (Figure 5).
The blank reaction was performed in ethanol without
catalyst and in presence of titania alone, separately. The
reaction was not completed even after 2 hours of heating,
and yield was very low (<25%) which indicated that the
reaction was mainly catalyzed by gold nanoparticles. It
was analyzed that the noncatalytic reactions also gave
the same Z isomer of the product with low yield after
prolonged heating (Table 1). It was reported that the
In the present study, we have used 5‐nitro (furan/thio-
phene) moiety in place of phenyl/p‐chlorobenzene and
observed only Z isomer of the product in all solvents stud-
ied. This stereoselectivity could be due to the presence of
nitro group on furan which causes electron withdrawing
effect on the acetylenic β carbon and facilitates the nucle-
ophilic attack of sulfur. In the presence of nano‐Au/TiO2
catalyst, the reaction was completed within 30 minutes in
ethanol compared with the conventional method. There-
fore, the reusable nano‐Au/TiO2 catalyzed reaction in
ethanol was chosen to be the efficient and sustainable
novel method for this hydrothiolation reaction.
The newly synthesized (Z)‐3‐[5‐nitro (furan/thio-
phene)‐2‐yl]‐1‐phenyl‐3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐
ylthio)prop‐2‐en‐1‐one 3a‐b were characterized by
hydrothiolation
of
benzene/p‐chlorobenzene
phenylacetylenic ketone using benzenethiol gave both E
and Z isomers in the ratio of 1:3 in benzene.[20]
TABLE 1 Screening of solvents for hydrothiolation under con-
ventional and catalytic conditions
Conventional Method
Time, Isolated
Nanocatalytic Method
Time, Isolated
Solvent
h
Yield, % Solvent
min
Yield, %
Benzene
THF
6
6
66
60
55
Benzene
90
90
90
80
83
84
THF/H2O (1:5)
tBuOH
6a
tBuOH/H2O
(1:5)
Water
6
2
52
Water
120
30
50
93
Ethanol
No
Ethanol
progress
FIGURE 5 Yield cycle of retraced catalyst for synthesis of
aIncomplete reaction.
compound 3a in ethanol under nitrogen gas atmosphere

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TURUKARABETTU AND KALLURAYA
FIGURE 6 ORTEP diagram of the molecule 3a viewed along c axis with thermal ellipsoids drawn at 50% probability
spectral and analytical techniques (Supporting Informa-
tion). The IR spectrum of 3a‐b showed absorption bands
at approximately 1630 cm−1 due to carbonyl stretching
Yield 93%; mp 200°C to 202°C; FT‐IR (KBr) νmax (cm−1):
3088 (alkene C─H), 1629 (C═O), 1595 (C═C), 1469 (NO2
1
assym. Str.), 1377 (NO2 sym. str.), 970 (C─S); H NMR
1
vibrations. In the H NMR spectra of 3a‐b, the alkene
(CDCl3, 400 MHz, δ ppm): 6.87 (d, 1H, J = 3.6 Hz,
nitrofuran‐3H), 7.23 (d, 1H, J = 3.6 Hz, nitrofuran‐4H),
7.97 (s, 1H, ═C─H), 7.46‐8.95 (m, 10H, Ar─H); 13C NMR
(CDCl3, 400 MHz, δ ppm): 112.6, 132.9, 115.1, 115, 129.1,
134.1, 136.4, 151.3, 122.9, 126.9, 128.2, 128.7, 129, 188.6
(C═O); MS (m/z): 419.50 [M+ + 1]; El. anal. for
C21H13N3O5S: Found: C 59.82; H 2.96; N 9.86; S 7.55; Cal-
culated: C 60.14; H 3.12; N 10.02; O 19.07; S 7.65.
proton of the α carbon was highly deshielded maybe
due to the vicinity of carbonyl group and the electron
withdrawing nitro group and appeared as singlet at δ
approximately 8 ppm. In 13C NMR spectrum, the car-
bonyl carbon was resonated at δ approximately 188.64
ppm. The spectral and analytical data for compounds 3a
and 3b are as follows.
(Z)‐3‐(5‐nitrofuran‐2‐yl)‐1‐phenyl‐3‐(5‐phenyl‐1,3,4‐
oxadiazol‐2‐yl)thia‐prop‐2‐en‐1‐one 3a: Yellow crystalline,
(Z)‐3‐(5‐Nitrothiophen‐2‐yl)‐3‐phenyl‐3‐(5‐phenyl‐
1,3,4‐oxadiazol‐2‐yl)thia‐prop‐2‐en‐1‐one 3b: Yellow
FIGURE 7 ORTEP diagram of the molecule 3b viewed along b axis with thermal ellipsoids drawn at 50% probability

TURUKARABETTU AND KALLURAYA
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crystalline, Yield 94%; mp 180°C; FT‐IR (KBr) νmax
(cm−1): 3105 (alkene C─H), 1635 (C═O), 1597 (C═C),
1473 (NO2 assym. Str.), 1330 (NO2 sym. str.), 902 (C─S);
1H NMR (DMSO, 400 MHz, δ ppm): 7.54 (d, 1H, J = 4.4
Hz, nitrothiophene‐3H), 8.03 (d, 1H, J = 4.4 Hz,
nitrothiophene‐4H), 8.15 (s, 1H, ═C─H), 8.15 (d, 1H, J
= 8.4 Hz, benzoyl‐2,6 H), 7.56‐8.04 (m, 8H, Ar─H); 13C
NMR (DMSO, 400 MHz, δ ppm): 122.8, 130.2, 136.4,
151.9, 126.9, 129.1, 129.3, 160.3, 166.7, 129.5, 129.7,
129.9, 130.2, 133, 134.6, 139.2, 146.8, 189.2 (C═O); MS
(m/z): 435.35 [M+]; El. anal. for C21H13N3O4S2: Found:
C 58.11; H 2.85; N 9.41; S 13.96. Calculated: C 57.92; H
3.01; N 9.65; O 14.70; S 14.73.
Further, single crystal data of compounds 3a and 3b
were collected by XRD analysis (CCDC No. 1494848,
1499444). The crystal structure of compounds 3a and 3b
was found to be monoclinic with space group P21/c
(Figure 6) and P21/n (Figure 7), respectively. The detailed
crystallographic data and CIF check report are given in
the electronic supporting information. For compound
3a, a portion of the molecule comprising the nitrofuran,
benzoyl ring, and the central segment (C9‐C11/O2)
connecting the two rings was almost planar as indicated
by the dihedral angles, 6.25(6)° (between nitrofuran and
benzoyl ring), 12.64(5)° (benzoyl ring and the central seg-
ment), and 12.42(9)° (nitrofuran and the central seg-
ment). The oxadiazole ring (C7/N1‐N2/C8/O1) made
dihedral angles of 16.78(10)°, 56.94(9)°, and 51.47(8)°
with phenyl (C1‐C6), nitrofuran (C18/O3/C19‐C21), and
benzoyl (C12‐C17) ring, respectively. The molecule was
twisted at sulfur atom (S1) with torsion angle C8‐S1‐C9‐
C10 being equal to −153.2(5). The torsion angle of the
alkene segment S1‐C9‐C10‐H10 was found to be
−178.47(5)°. Therefore, the single crystal XRD analysis
confirmed the anti‐addition of thiol to the alkyne and for-
mation of the Z isomer.
used to observe the changes in bond parameters of acety-
lenic ketone after hydrothiolation. The ─C≡C─ bond
length 1.210(8) Å of acetylenic ketone 2a was increased
to 1.348(8) Å for ─C═C─ of 3a due to change of carbon
hybridization from sp to sp2 state. The large change in
the bond angles of C18‐C9‐C10 and C9‐C10‐C11 of 3a
indicated the deviation from linearity to that of molecule
2a.
3.3 | DFT molecular model study
The interaction of acetylenic ketone and gold nanoparti-
cle was studied by the PWrelax calculations considering
the reactant and gold atom in the gas phase (Figure 8A‐
F). Though the reaction was carried out in presence of
plural gold atoms nanoparticle, the adduct forming center
of acetylenic ketone was identified in gas phase interac-
tion with single gold atom by simplifying the quantum
mechanical calculations of heterogeneous catalyst
model.[47] The position of gold atom was located over
acetylene triple bond in such a way that it has equal prob-
ability to form bond either with α or β carbon atom
(Figure 8A) depending on the electron density over it.
The relax calculations showed that the electropositive
gold would preferentially attack on α carbon. This could
be due to more electronegativity of α carbon compared
with β carbon and possible electron coordination with
oxygen of the carbonyl group (Figure 8F). This calcula-
tion indicated that α carbon can have a strong adsorbing
interaction with plural nanogold compared with β car-
bon. The changes in ─C≡C─ and ≡C─Au bond lengths
during the interaction are labeled in the same figure.
On adsorption, the bond length between Au and α carbon
of acetylenic ketone was found to be 2.079 Å.
The carbon‐carbon triple bond length was increased to
1.2792 Å from 1.2194 Å. A video content showing interac-
tion of acetylenic ketone with gold in gas phase is
The single crystal structure of acetylenic ketone 2a was
reported from our laboratory,[46] and these data were
FIGURE 8 (A‐F) Catalytic interactions
of acetylenic ketone and gold obtained
from PWrelax calculation

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TURUKARABETTU AND KALLURAYA
available with this article in the Supporting Information.
The pdos charge calculation of acetylenic ketone was car-
ried out to identify the partial charges on α and β carbons
of acetylenic ketone. The partial charge on α and β car-
bon was found to be 3.9569e and 3.9511e, respectively,
which indicated that the ─C≡C─ bond is least polar.
However, on adsorption of acetylenic ketone on gold,
the partial charge on α and β carbon was found to be
4.0689e and 3.9656e, respectively. This indicated that
the ─C≡C─ bond was more polar in nature when
adsorbed over gold, and β carbon had a partial positive
charge. These changes in polarity of the acetylene bond
would be responsible for the faster rate of product forma-
tion in presence of nano‐Au/TiO2 than in conventional
synthesis. Hence, during hydrothiolation reaction, possi-
ble nucleophilic attack of 5‐aryl‐1,3,4‐oxadiazole‐2‐thiol
on β carbon atom of acetylenic ketone takes place and
addition of proton to the α carbon. Indeed, gold nanopar-
ticles would prefer an aqueous solvent for this reaction.
The structures of 5‐phenyl‐1,3,4‐oxadiazole‐3‐thiol 1,
5‐phenyl‐1,3,4‐oxadiazole‐2‐thiol 2, and (Z)‐3‐(5‐nitrofu-
ran‐2‐yl)‐1‐phenyl‐3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐ylthio)
prop‐2‐en‐1‐one 3a were solved by running the relax pro-
gram separately and used for the frontier molecular
orbital calculations. The frontier HOMO and LUMO dia-
grams of compounds 1 and 2a were obtained from DFT
FIGURE 10 The overlap of molecular orbitals between
molecules 1 and 2a
calculations, which are shown in Figure 9 with the
energy level values and Fermi energy (EF) corresponding
to the HOMO and LUMO. The frontier molecular orbital
calculation of 1 showed that the HOMO present over
FIGURE 9 The frontier highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) diagrams of
molecules 1 and 2a obtained from DFT calculations

TURUKARABETTU AND KALLURAYA
9 of 11
sulfur. Similarly, the compound 2a adsorbed on gold (Au‐
2a) showed LUMO on ─C≡C─ bond and a node in
between the alkyne carbons.
The HOMO and LUMO of reactants indicated the pos-
sible overlap of molecular orbitals of sulfur and β carbon
of acetylenic ketone to give compound 3a as shown in
Figure 10. Further, the HOMO calculation of molecule
3a indicated that the sulfur had occupied levels which
could be due to the migration of proton to α carbon of
the acetylenic ketone (Figure 11).
A possible conformer of compound 3a was predicted
using DFT calculation is shown in Figure 12 and labeled
it as molecule 4. The PWscf calculation of 3a and 4 gave
the molecular energies −6505.256 × 105 and −6505.262
× 105 J/mol, respectively. This indicated that compound
3a was energetically stable than 4 by −600 J/mol. The
molecule 1 had molecular energy equal to −2525.291 ×
105 J/mol and molecule 2a had molecular energy equal
to −3978.619 × 105 J/mol. The sum of these molecular
energies for 3a was found to be −6503.91 × 105 J/mol.
Therefore, the theoretical energy of formation of 3a was
found to be 134.6 kJ/mol. The theoretical binding energy
of molecule 3a was found to be −22.25 MJ/mol.
A possible ground state energy structure of E isomer of
compound 3a was predicted using DFT calculations, if
the reaction had progressed in a syn addition manner.
The E isomer 5 is shown in Figure 12. The formation of
E isomer may require higher energy for the distortion of
benzoyl and nitrofuran group from the planarity com-
pared with the formation of 3a which involves the migra-
tion of smaller hydrogen ion to the α carbon in solvent
medium.
The selected geometrical parameters of 3a (Table S1)
obtained from the single crystal XRD technique and
DFT calculation are plotted as linear correlation diagrams
as shown in Figure 13. The agreement between these
FIGURE 11 The highest occupied
molecular orbital (HOMO) and lowest
unoccupied molecular orbital (LUMO)
diagrams of molecule 3a
FIGURE 12 The ground state energy
structures of molecule 4 and 5 predicted
from density functional theory (DFT)
FIGURE 13 The linear correlation diagrams for the theoretical (density functional theory [DFT]) and experimental (X‐ray diffraction
[XRD]). (A) Bond length and (B) bond angles of compound 3a

10 of 11
TURUKARABETTU AND KALLURAYA
FIGURE 14 Probable mechanism for
catalytic hydrothiolation of acetylenic
ketone
values has been evaluated by calculating the root‐mean‐
square deviation (RMSD). The RMSD value of bond
lengths and bond angles was found to be 0.01211 Å and
1.2911°, respectively.
sustainable protocol would be useful in construction of
C─S bonds with multiple bioactive heterocyclic
compounds.
A possible mechanism for hydrothiolation reaction has
been proposed based on the analogy with DFT calcula-
tions and experimental evidences as shown in Figure 14.
Gold is more alkynophilic than oxophilic in nature and
hence coordinates with alkynes bond (─C≡C─) (I) and
reduces the electron density. On adsorption, the alkyne
group became more polar in nature. This enables the
nucleophilic attack of thiol sulfur of compound 1 on β
carbon (II). Then α carbon would receive the proton from
SH/NH of compound 1 by anti‐addition to form a Z iso-
mer (III) of 3a.
ORCID
Balakrishna Kalluraya
7178
https://orcid.org/0000-0003-0442-
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