N-bromosuccinimide (NBS)-promoted, three-component synthesis of α,β-unsaturated isoxazol-5(4H)-ones, and spectroscopic investigation and computational study of 3-methyl-4-(thiophen-2-ylmethylene)isoxazol-5(4H)-one

Article abstract of DOI:10.1007/s11164-014-1857-5

A three-component, NBS-promoted synthesis of α,β-unsaturated isoxazol-5(4H)-ones by reaction of aromatic aryl or hetero-aryl aldehydes, hydroxylamine hydrochloride, and 1,3-dicarbonyl compounds (ethyl acetoacetate or ethyl 4-chloroacetoacetate), under mild reaction conditions at room temperature is described. This simple, efficient, and clean reaction is an expeditious means of obtaining the corresponding isoxazol-5(4H)-one derivatives in good to high yields. Geometrical properties and vibrational wavenumbers of 3-methyl-4-(thiophen-2-ylmethylene)isoxazol-5(4H)-one (MTISO) were predicted by use of density functional theory (DFT) by use of the B3LYP level with the 6-311++G(d,p) and 6-311++G(2d,p) basis sets. Results indicate that the B3LYP method enables satisfactory prediction of vibrational frequencies and structural data. The absorption spectra of MTISO in solvents of different polarity were studied at room temperature. The UV-visible spectrum of the compound was recorded and such electronic properties as the energies of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were determined by the time-dependent DFT (TD-DFT) approach. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization was studied by NBO analysis. A molecular electrostatic potential map (MEP) of the compound was also studied to predict reactive sites. Reactivity descriptors, Fukui functions, and electrophilic sites were found and are discussed. The thermal stability of MTISO was studied by thermogravimetric analysis (TGA).

Full text of DOI:10.1007/s11164-014-1857-5

Res Chem Intermed
DOI 10.1007/s11164-014-1857-5
N-bromosuccinimide (NBS)-promoted, three-
component synthesis of a,b-unsaturated isoxazol-5(4H)-
ones, and spectroscopic investigation and computational
study of 3-methyl-4-(thiophen-2-ylmethylene)isoxazol-
5(4H)-one
•
Hamzeh Kiyani Ayub Kanaani Davood Ajloo
•
•
•
Fatemeh Ghorbani Mohammad Vakili
Received: 11 September 2014 / Accepted: 19 October 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract A three-component, NBS-promoted synthesis of a,b-unsaturated iso-
xazol-5(4H)-ones by reaction of aromatic aryl or hetero-aryl aldehydes, hydroxyl-
amine hydrochloride, and 1,3-dicarbonyl compounds (ethyl acetoacetate or ethyl
4-chloroacetoacetate), under mild reaction conditions at room temperature is
described. This simple, efficient, and clean reaction is an expeditious means of
obtaining the corresponding isoxazol-5(4H)-one derivatives in good to high yields.
Geometrical properties and vibrational wavenumbers of 3-methyl-4-(thiophen-2-
ylmethylene)isoxazol-5(4H)-one (MTISO) were predicted by use of density func-
tional theory (DFT) by use of the B3LYP level with the 6-311??G(d,p) and
6-311??G(2d,p) basis sets. Results indicate that the B3LYP method enables sat-
isfactory prediction of vibrational frequencies and structural data. The absorption
spectra of MTISO in solvents of different polarity were studied at room tempera-
ture. The UV–visible spectrum of the compound was recorded and such electronic
properties as the energies of the highest occupied molecular orbital (HOMO) and
the lowest unoccupied molecular orbital (LUMO) were determined by the time-
dependent DFT (TD-DFT) approach. The stability of the molecule arising from
hyper-conjugative interaction and charge delocalization was studied by NBO ana-
lysis. A molecular electrostatic potential map (MEP) of the compound was also
H. Kiyani (&) ꢀ A. Kanaani ꢀ D. Ajloo (&) ꢀ F. Ghorbani
School of Chemistry, Damghan University, 36715-364 Damghan, Iran
e-mail: hkiyani@du.ac.ir
D. Ajloo
e-mail: ajloo@du.ac.ir
D. Ajloo
Department of Physical Chemistry, School of Chemistry, College of Science, University of Tehran,
Tehran, Iran
M. Vakili
Department of Chemistry, Faculty of Science, Mashhad University, Mashhad, Iran
123

H. Kiyani et al.
studied to predict reactive sites. Reactivity descriptors, Fukui functions, and elec-
trophilic sites were found and are discussed. The thermal stability of MTISO was
studied by thermogravimetric analysis (TGA).
Keywords Isoxazol-5(4H)-ones ꢀ 3-Methyl-4-(thiophen-2-ylmethylene)isoxazol-
5(4H)-one ꢀ DFT ꢀ NMR and UV spectra ꢀ Fukui function ꢀ NBO analysis
Introduction
The isoxazol-5(4H)-ones and their derivatives have applications in many areas, for
example liquid crystalline materials [1], organic synthesis [2], light-conversion
molecular devices [3], filter dyes in photographic films [4], and optical storage and
nonlinear optical research [5]. Several substituted isoxazoles have been shown to
have a broad range of biological properties, for example anti-obesity [6], analgesic
[7], anti-inflammatory [8], and antitumor [9] activity. The isoxazole backbone is
also a structural component of a variety of natural products, for example, muscimol
[10], cycloserine [11], ibotenic acid, and isoxazol-4-carboxylic acid [12]. For this
reason, much research has been focused on synthesis of isoxazoles and study of their
properties.
In recent years, a,b-unsaturated isoxazol-5(4H)-ones have been prepared via a
three-component condensation of b-oxoesters, hydroxylamine hydrochloride, and
aromatic aldehydes by use of catalytic amounts of sodium benzoate [13], sodium
sulfide [14], sodium silicate [15], DABCO [16], nano Fe2O3, clinoptilolite, and
H3PW12O40 [17]. Other conditions have also been reported in the literature for this
three-component reaction, including the use of sodium acetate and visible light [18],
pyridine under ultrasonic irradiation [19, 20], pyridine under reflux [21, 22], and
catalyst-free/grinding or heating [23]. We have synthesized several a,b-unsaturated
isoxazol-5(4H)-one derivatives by using sodium ascorbate [24], sodium citrate [25],
sodium saccharin [26], sodium tetraborate [27], sodium azide [28], boric acid [29],
and potassium phthalimide [30] as catalysts. Although a,b-unsaturated 4H-isoxazol-
5-ones have been synthesized, no results of three-component cyclocondensation of
aryl aldehydes (1a–n), hydroxylamine hydrochloride (2), and b-oxoesters (3a–b),
using NBS as a catalyst, have yet been reported in the literature. In the work
discussed in this report, NBS was used as an organic catalyst for synthesis of a,
b-unsaturated isoxazol-5(4H)-ones in aqueous media (Scheme 1).
1
In this study, FT-IR, H NMR, 13C NMR, and UV spectral investigation of
MTISO were performed by use of density functional theory (DFT). NBO analysis
was performed to provide valuable information about a variety of intermolecular
interactions. The molecular structure, EHOMO (energy of the highest occupied
molecular orbital), ELUMO (energy of the lowest unoccupied molecular orbital),
LUMO–HOMO energy gap (DE), global hardness (g), softness (S), electronegativity
(v), dipole moment (l), polarizabilities (hai), anisotropy of the polarizabilities
(hDai), first-order hyperpolarizabilities (hbi), Fukui functions, molecular
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
O
Ar
R
O
NBS, 5 mol%
EtO2C
R
+ NH2OH.HCl +
Ar
H
N
H2O, r.t.
O
O
R = H (3a), Cl (3b)
1a-n
2
3a-b
4a-t
Scheme 1 Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones promoted by NBS
electrostatic potential maps (MEP), and thermodynamic data (molecular energy (E),
heat capacity (Cp0;m), entropy (Sm0 ) and enthalpy (Hm0 )) were calculated and are
discussed.
Experimental
General
Mid-IR spectra in the range 4,000–400 cm-1, with spectral resolution of 2 cm-1
,
were acquired by use of a Perkin–Elmer RXI Fourier-transform spectrophotometer
with the KBr pellet technique (solid phase); results from 16 scans were averaged.
Ultraviolet absorption spectra in the range 200–800 nm were acquired by use of a
Perkin–Elmer Lambda 25 spectrophotometer. NMR spectra were recorded at
ambient temperature on a Bruker Avance DRX 400 MHz with CDCl3 or DMSO-d6
as solvent. Melting points were measured on a Buchi 510 melting point apparatus
and are uncorrected. Chemicals were obtained from Merck and Fluka and were used
without further purification, with the exception of NBS, which was purified by
recrystallization from water. The progress of reactions was monitored by thin-layer
chromatography (TLC) on silica gel 60 GF254 aluminium sheets, with ethyl acetate–
petroleum ether (1:3) as mobile phase. The spots were exposed by UV light and
iodine vapor. To determine thermal stability, thermal analysis (TGA and DTA) was
performed with a Perkin–Elmer instrument. Analysis was performed in an
atmosphere of nitrogen at a heating rate of 25°/min for 10 min in the temperature
range 25–750 °C for TGA.
Typical procedure for synthesis of a,b-unsaturated isoxazol-5(4H)-ones (4a–t)
A mixture of equimolar quantities of hydroxylamine hydrochloride (0.07 g,
1 mmol) and ethyl acetoacetate (0.130 g, 1 mmol) in 5 mL water was stirred for
5 min. Thiophene-2-carbaldehyde (0.112 g, 1 mmol) and NBS (5 mol%) were then
added and the reaction mixture was stirred at room temperature for 95 min. The
solid products were isolated by simple filtration, washed with water (5 mL), then
recrystallized from ethanol. Synthesis of compounds 4a–t has been reported in our
previous papers, so the products are known; their identity was confirmed by
comparison of their physical and spectral data with those available in our recent
papers [24–30].
123

H. Kiyani et al.
Spectral data for 3-methyl-4-(thiophen-2-ylmethylene)isoxazol-5(4H)-one: 1H
NMR (400 MHz, CDC13): d 2.32 (s, 3H), 7.29 (t, J = 4.8 Hz, 1H), 7.65 (s, 1H),
7.95 (d, J = 4.8 Hz, 1H), 8.13 (d, J = 3.6 Hz, 1H); 13C NMR (100 MHz, CDC13):
d 11.5, 114.6, 128.9, 136.5, 139.2, 139.6, 141.5, 160.7, 168.7.
Calculations
The molecular structure of MTISO and the corresponding vibrational harmonic
frequencies were calculated by use of the B3LYP method, combined with the
6-311??G (d, p) and 6-311??G(2d,p) basis sets, in the Gaussian 03 software
package [31], without any constraint on geometry. B3LYP uses Becke’s three-
variable hybrid functional method [32] with the Lee–Yang–Parr correlation functional
(LYP) [33, 34]. Assignment of calculated wavenumbers was aided by the animation
option of Gaussview software, which gives a visual presentation of the vibrational
modes [35]. In this investigation we found that the calculated frequencies were slightly
greater than the fundamental frequencies. Such discrepancies are usually corrected
either by computing anharmonic corrections explicitly [36] or by introducing a scale
factor. In this study selective scaling factors were used: 0.9961 for wavenumbers
\1,700 cm-1, 0.9556 for wavenumbers [1,700 cm-1 at 6-311??G(d, p), and
0.9963 for wavenumbers\1,700 cm-1 and 0.9959 for wavenumbers[1,700 cm-1 at
6-311??G(2d,p) [37]. Detailed interpretation of the vibrational spectra of MTISO
was performed on the basis of calculated potential energy distribution (PED).
Assignments of the experimental frequencies are based on the observed band
frequency and intensity changes in the infrared spectra, and confirmed by establishing
one-to-one correlation between observed and theoretically calculated frequencies.
The electronic properties were also calculated by use of the B3LYP method of the
time-dependent DFT (TD-DFT) [38], on the basis of the optimized structure. TD-DFT
has been proved to be a powerful and effective computational tool for study of ground
and excited state properties by comparison with available experimental data. Hence,
we used TD-DFT to obtain wavelengths and compared the calculated results with
experimental UV absorption values. To understand intramolecular delocalization and
hyperconjugation, NBO calculations [38] were performed by use of NBO 3.1
software as implemented in the Gaussian 03W package at the DFT/B3LYP level. The
molecular electrostatic potential (MEP) surface was plotted over the optimized
geometry to elucidate the reactivity of the MTISO molecule. The HOMO and LUMO
were calculated by use of the B3LYP/6-311??G(2d,p) method. The Lorentzian
function was used for deconvolution of IR spectra, by use of the Genplot package.
Results and discussion
Optimization of reaction conditions and scope of the reaction
To initiate our study, we checked the three-component reaction of 4-hydroxybenz-
aldehyde (1h), hydroxylamine hydrochloride (2), and ethyl acetoacetate (3a) as
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
model reaction. The effects of the amounts of catalyst and solvents were
investigated; the experimental results are summarized in Table 1. Yields of product
4h were 80, 91, and 95 %, respectively, when 1, 2.5, and 5 mol% NBS were used
(Table 1, entries 2–4). On the basis of reaction time (100 min) and yield (95 %),
5 mol% of NBS provided the best result and was thus selected as the optimum
quantity for promotion of the reaction. Use of larger amounts of NBS resulted in
only trace amounts of the product (Table 1, entries 5 and 6).
We also screened a variety of solvents (EtOH, acetone, hexane, 1,4-dioxane,
cyclohexane, THF, 1:1 (v/v) H2O–EtOH, and 1:1 (v/v) H2O–acetone) for this
reaction, with 5 mol% NBS as catalyst (Table 1, entries 7–14). This investigation
revealed that reaction in water resulted in the best reaction time and yield, so water
was selected as the optimum solvent. Water is also an environmentally benign
solvent. When the reaction was performed under solvent-free conditions the yield in
120 min was lower (Table 1, entry 15). Increasing the reaction temperature to 50,
Table 1 Screening of the effects of solvents and amounts of NBS on the synthesis of 4-(4-hydroxyb-
enzylidene)-3-methylisoxazol-5(4H)-one (4h)
O
O
H
HO
CH3
NBS
HO
+ NH2OH.HCl +
CO2Et
H3C
Solvent
N
O
O
1h
2
3a
4h
Entry
Solvent
Amount of
NBS (mol%)
Time (min)
Yield (%)a
1
H2O
–
120
120
110
100
120
120
120
120
120
120
120
120
120
120
120
Trace
80
2
H2O
1
3
4b
H2O
2.5
5
91
H2O
95
5
H2O
10
15
5
Trace
Trace
45
6
H2O
7
C2H5OH
Acetone
Hexane
8
5
15
9
5
21
10
11
12
13
14
15
1,4-Dioxane
Cyclohexane
THF
5
20
5
Trace
Trace
60
5
H2O/C2H5OH (1:1)
H2O/Acetone (1:1)
Solvent-free
5
5
20
5
40
Reaction conditions: 4-hydroxybenzaldehyde 1h (1 mmol), hydroxylamine hydrochloride 2 (1 mmol),
ethyl acetoacetate 3a (1 mmol), water (5 mL), room temperature
a
Isolated yield of product
b
Optimized conditions are shown in bold
123

H. Kiyani et al.
Table 2 Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones (4a–t) from aryl aldehydes
(1a–n), hydroxylamine hydrochloride (2) and two b-oxoesters (3a, b) promoted by NBS in water at room
temperature
Entry
Aldehyde (1)
R
Product (4)
Time (min)
Yielda (%)
m.p. (°C)b
1
C6H5CHO 1a
H
4a
4b
4c
4d
4e
4g
4h
4i
140
100
80
91
92
95
96
90
94
95
92
84
91
92
84
92
86
90
93
93
95
92
140–142
135–137
175–177
213–215
198–200
199–201
210–211
222–223
239–241
143–145
142–144
266–267
242–244
183–186
175–177
142–145
183–186
179–180
146–148
2
4-CH3C6H4CHO 1b
4-CH3OC6H4CHO 1c
4-OH-3-CH3OC6H3CHO 1d
2-OHC6H4CHO 1e
3-OHC6H4CHO 1g
4-OHC6H4CHO 1h
4-(NMe)2C6H4CHO 1i
2-Furyl 1j
H
3
H
4
H
70
5
H
130
120
100
90
6
H
7
H
8
H
9
H
4j
120
100
100
40
10
11
12
13
14
15
16
17
18
19
2-Thienyl 1k
H
4k
4l
3-Thienyl 1l
H
4-OH-3-NO2-C6H3CHO 1m
3-Coumarinyl 1n
H
4m
4n
4o
4p
4q
4r
4s
H
120
40
C6H5CHO 1a
Cl
Cl
Cl
Cl
Cl
Cl
4-CH3OC6H4CHO 1c
4-OH-3-CH3OC6H3CHO 1d
4-OHC6H4CHO 1h
4-(NMe)2C6H4CHO 1i
2-Thienyl 1k
45
25
20
25
4t
30
Reagents and conditions: aryl aldehyde 1 (1 mmol), hydroxylamine hydrochloride 2 (1 mmol), b-keto-
ester 3 (1 mmol), water (5 mL), room temperature
a
All yields are of pure products
b
Melting points were obtained from Refs. [24–30]
70, and 100 °C had no significant effect on the yield of the product or on reaction
rate.
After optimization of the reaction conditions, we turned our attention toward the
scope of the reaction, by using a variety of aryl aldehydes with different substituents
on the benzene ring, and p-excessive heterocyclic aldehydes (1j–l), and ethyl
acetoacetate (3a) or chloroethyl acetoacetate (3b) to construct a,b-unsaturated
isoxazol-5(4H)-ones (4a–t). As is apparent from Table 2, with substituted
benzaldehydes containing electron-donating groups at the m- or p-position of the
benzene ring and with heterocyclic aldehydes this three-component reaction
proceeded efficiently to give the corresponding products in good to excellent yields
and with reasonable reaction times (entries 1–19 in Table 2).
Although we did not investigate the mechanism of this reaction, on the basis of
the literature [13–30] we propose the mechanism outlined in Scheme 2 for
formation of a,b-unsaturated isoxazol-5(4H)-ones (4a–t). According to this
mechanism, NBS effectively catalyzes the Knoevenagel condensation between an
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
HO
HO
N
O
O
O
N
OH
NH2OH.HCl
O
R
R
R
O
O
O
5
6
3
O
O
H
+
H
N Br
Ar
N
+
BrO
1
Ar
7
O
O
HO
Ar
H
O
N
O
O
HO
H
O
N
O
R
N
R
Br
H
-O
N
O
-
O
Ar
BrO
H
H
O
9
H
Proton transfer
Dehydration
8
H
H
HO
N
O
N
O
N
O
N
O
O
O
R
R
R
R
O
O
O
O
-EtOH
Ar
4a-t
Ar
10
Ar
11
Ar
12
Scheme 2 A plausible mechanism for the synthesis of a,b-unsaturated isoxazol-5(4H)-ones (4a–t)
aldehyde and an active methylene compound (3). Intramolecular O-attack
cyclization of 10 to 11, proton exchange between 11 and 12, then deethanolization
lead to formation of the target products.
Geometrical data
The optimized geometrical data for MTISO, calculated at B3LYP/6-311??G(d,p)
and B3LYP/6-311??G(2d,p) levels of theory are presented in Table 3, in
accordance with atom numbering scheme given in Fig. 1.
The optimized structure can only be compared with other similar systems for
which the crystal structures have been solved [39, 40]. For title compound, it was
found that the carbon–carbon bond lengths of the molecular skeleton was
˚
˚
intermediate between typical C–C single (1.54 A) and C=C double (1.34 A) bonds.
The p electrons were delocalized throughout the molecule, and the methyl group in
the isoxazolone ring was involved in molecular conjugation. For MTISO, all of the
torsion angles were close to 180° or 0°, which indicates that the molecular
framework of title compound is planar. The torsion angles C4–C9–C11–C16 and C3–
C4–C9–C11 (-179.91° and 0.06°) show that the thiophene group and isoxazole
˚
˚
group are nearly coplanar. The C2–C3 (1.41 A) and C9–C4 (1.43 A) bond lengths
˚
are shorter than those of C11–C12 (1.48 A), C11–C16 (1.45 A), and C16–C17 (1.49 A)
˚
˚
123

H. Kiyani et al.
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
123

H. Kiyani et al.
Fig. 1 Theoretical optimized geometric structure and atom numbering for MTISO
(Table 3), because of delocalization of the electron density of the C=C of thiophene.
The bond angles between C3=C4–C9 (132.52°) and C9–C11–C16 (125.39°) are larger
than 120°, indicating the presence of hyper-conjugation.
The difference between the C11–C12 and C11–C16 bond lengths arises because of
the different polarity of the groups attached to them. Cheng et al. [40] reported N–O
˚
and C=N bond lengths of approximately 1.44 A and 1.28 A, respectively. In our
˚
˚
study C=N bond lengths were computed 1.29 A and N–O bond lengths as
˚
approximately 1.43 A, in good agreement with experimental data and literature
values. It seems the B3LYP/6-311??G(2d,p) method correctly predicted bond
lengths, bond angles, and torsion angles; this is useful for investigation of the
characteristics of structurally related isoxazoles.
The potential energy profile as a function of the dihedral angle between the
isoxazole and thiophene rings (C11=C9–C4–C3) was obtained by use of the DFT
method; a plot of the potential energy surface (PES) for this molecule is shown in
Fig. 2. During the calculations, all the geometrical parameters were simultaneously
relaxed and the dihedral angle was varied in steps of 10° from 360° and reduced up
to zero. The optimized structure was obtained at 0.06° for the C11=C9–C4–C3
dihedral angle; the corresponding minimum energy was -950.5347 Hartree, which
implies that the structure obtained was at the global minimum.
Vibrational analysis
MTISO consists of 20 atoms which have 54 normal modes. These normal modes
were assigned in accordance with the detailed motion of the individual atoms. The
observed FTIR spectrum of MTISO is shown in Fig. 3.
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
Fig. 2 PES scan for the dihedral angle C11=C9–C4–C3, obtained by use of the DFT/B3LYP/6-
311??G(d,p) method
Fig. 3 FTIR spectrum of 3-methyl-4-thiophen-2-ylmethylene-4H-isoxazol-5-one
The observed IR bands, calculated frequencies, IR intensities, Raman activity,
and normal mode descriptions (characterized by PED) of the stable conformer of
MTISO are depicted in Table 4. For clear observation of these bands, deconvolution
techniques can be used for the IR spectrum. A deconvoluted IR spectrum of MTISO
123

H. Kiyani et al.
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
123

H. Kiyani et al.
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
100
80
60
40
20
0
400
600
800
1000
1200
1400
1600
1800
Wavenumber (cm–1)
Fig. 4 Deconvoluted IR spectrum of MTISO (in the 1,800–400 cm-1 region)
is depicted in Fig. 4. The ultimate purpose of this part of the study was assignment
of vibrational wave numbers. Vibrational analysis of MTISO was performed on the
basis of the characteristic vibration modes of the C–O, C=O, C=N, N–O, C–S, CH,
and CH3 groups of the compound.
The C–O stretching vibrations of isoxazole produce strong bands in the
1,126–1,084 cm-1 region of the spectrum [40]. According to our deconvolution
results, the IR spectrum of MTISO contains medium FT-IR bands arising from C–O
stretching vibrations at 1,130 cm-1 (Fig. 4) and 1,166 cm-1 (B3LYP). Normally,
carbonyl group vibrations occur in the region 1,780–1,680 cm-1 [41]. In this study,
the C=O stretching vibration is assigned at 1,736 cm-1 in the FT-IR spectrum, with
very strong intensity. The bands observed at 512 and 531 cm-1 (DFT) were
assigned to C=O in-plane bending vibrations.
Brancatelli et al. [42] reported a value 1,571 cm-1 for the isoxazol-5(4H)-one
C=N stretching mode. Deconvoluted IR spectra of MTISO indicate the presence of
three bands at 1,612, 1,602, and 1,576 cm-1 in IR spectra, and the bands at 1,629,
1,613, 1,531 cm-1 given by calculation are assigned as tC=N (Table 4). In The
N–O stretching skeletal bands are expected in the range 878 cm-1 [39]. A band
observed at 876 cm-1 in the FT-IR spectrum is assigned to the N–O stretching
vibration mixed with C–CH3 stretching.
123

H. Kiyani et al.
C–H stretching of methyl group occurs at lower frequencies than for that in the
aromatic ring (3,100–3,000 cm-1). For MTISO B3LYP calculations give taCH3 at
3,116, 3,115, and 3,070 cm-1 and tsCH3 at 3,020 cm-1. The bands at 3,077, 2,960,
2,926, and 2,856 cm-1 in the IR spectrum are assigned as taCH3 and tsCH3. For
many molecules the symmetric deformation appears in the range 1,380 25 cm-1
with intensity varying from medium to strong [43]. For MTISO, the scissoring
modes of the CH3 group were calculated to be at 1,476, 1,426, and 1,403 cm-1
(B3LYP); the measured values (IR spectrum) were 1,509, 1,420, and 1,408 cm-1
.
The rocking vibrations of the CH3 group are usually observed in the region
1,070–1,010 cm-1 [44]. The bands at 1,030, 998, and 981 cm-1 in the IR spectrum,
and three bands at 1,061, 1,037, and 1,005 cm-1 (B3LYP) were assigned as qCH3
mode for MTISO. The twisting modes were not observed in the FT-IR spectrum
because they appear at very low frequency. The band at 166 cm-1 (B3LYP) was
assigned as the twisting mode sCH3.
The thiophene ring C–H stretching vibrations were calculated to be at 3,243,
3,216, and 3,195 cm-1 and observed at 3,549, 3,465, and 3,420 cm-1 in the FT-IR
spectrum. The C–H out-of-plane bending modes of thiophene derivatives are
observed in the region 600–900 cm-1. Aromatic C–H out-of-plane bending of the
thiophene ring is assigned to medium to weak bands observed at 986, 932, 876, and
624 cm-1. Aromatic C–H in-plane bending modes of thiophene and its derivatives
are observed in the region 1,360–1,080 cm-1 [44]. According to our deconvolution
results, C–H in-plane bending modes of the thiophene ring are predicted at 1,216,
1,092, 1,072, and 1,037 cm-1
.
Identification of C–S stretching vibration is difficult and uncertain. Four peaks
recorded at 608.8, 753.5, 839.5, and 872.8 cm-1 have been assigned to C–S
stretching [45] on the basis of potential energy distributions (PED) obtained from
DFT calculations. Coruh et al. [46] assigned this mode at 834 cm-1 in the FT-IR
spectrum. In our study, experimental C–S stretching vibrations were observed at
866 and 776 cm-1
.
It is apparent from Fig. 5 that correlation between the theoretical and
experimental FT-IR spectra is excellent, i.e. experimental fundamentals correlate
well with B3LYP results. The correlation plot is expressed by the linear equation,
y = 55.063 ? 0.9387x, where y is the experimental wavenumber and x the
calculated wavenumber (cm-1). The correlation coefficient (R2 = 0.9989) also
shows there is good agreement between experimental and calculated results.
NBO analysis
Natural bond orbital (NBO) analysis provides a description of the structure of a
conformer as a set of localized bonds, antibonds, and Rydberg extra valence
orbitals. NBO analysis was used to determine the interaction between bond orbitals,
electron delocalization, bond-bending effect, and intramolecular charge transfer
(ICT). The second-order Fock matrix was used to evaluate donor–acceptor
interactions in the NBO analysis [47]. The interactions result in loss of occupancy
from the localized NBO of the idealized Lewis structure into an empty non-Lewis
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
Fig. 5 Correlation of calculated and experimental IR frequencies for MTISO
orbital. For each donor (i) and acceptor (j) the stabilization energy E(2) associated
with the delocalization i ? j is determined as:
2
ðFijÞ
Eð2Þ ¼ DEij ¼ qi
ð1Þ
2
ðEj ꢁ EiÞ
where qi is the donor orbital occupancy, Ei and Ej are diagonal elements, and Fij is
the off-diagonal NBO Fock matrix element [48]. In NBO analysis, a large E(2) value
is indicative of strong interaction between electron donors and electron acceptors,
and the greater the extent of conjugation of the whole system, the greater is the
interaction given by NBO (Table 5).
Second-order perturbation theory analysis of the Fock matrix in NBO revealed
strong intermolecular hyper-conjugative interactions as a result of orbital overlap
between n(O) and n(S) with the p*(C–O), p*(C–N), and p*(C–C) bond orbitals,
resulting in ICT stabilization of the system.
The strong intermolecular hyper-conjugative interaction pC3–C4?p*(C1–C2 and
C9–C11) of C3–C4 in MTISO increases the ED (0.24 and 0.17 e) and thus weakens
the respective bonds, leading to stabilization of 30.54 and 34.60 kcal mol-1. The
hyper-conjugative interaction in S5 of n2(S5)?p*(C1–C2 and C3–C4) increases the
ED (0.24 and 0.28 e) and weakens the respective bonds leading to stabilization of
40.66 and 30.61 kcal mol-1. There is a strong intermolecular hyper-conjugative
interaction in MTISO from O13 of n2(O13)?r*(C11–C12), r*(C12–O14) which
increases the ED (0.07 and 0.10 e) and weakens the respective bonds, leading to
stabilization of 32.14 and 50.63 kcal mol-1, and also hyper-conjugative interaction
for O14 of n2(O14)?p*(C16–N15, C12–O13) which increases the ED (0.14 and 0.19
e) and weakens the respective bonds, C16–N5 and C12–O13, leading to stabilization
123

H. Kiyani et al.
Table 5 Second-order perturbation theory analysis of the Fock matrix in NBO analysis of MTISO at the
B3LYP/6-311??G(2d,p) level
Donor (i)
Type
ED/e
Acceptor
(j)
Type
ED/e
E(2)a
(kcal mol-1
E(j) - E(i)b
(a.u.)
F(i, j)c
(a.u.)
)
C1–C2
p
r
p
–
p
–
–
p
r
p
r
r
–
r
r
r
p
–
p
–
p
–
1.86
1.98
1.81
–
C3–C4
C2–H7
C9–C11
C1–C2
C3–C4
p*
r*
p*
–
0.28
0.01
0.17
0.24
0.28
0.14
0.19
0.17
0.10
0.17
0.04
0.02
0.04
0.04
0.14
00.2
0.07
0.10
0.14
0.19
0.28
0.24
37.40
3.91
0.56
1.43
0.56
0.55
0.57
0.58
0.58
15.15
1.43
0.71
1.45
5.40
1.72
1.50
0.92
0.92
1.05
0.98
0.64
0.64
0.51
0.51
0.13
0.07
0.13
0.12
0.09
0.11
0.11
0.09
0.08
0.07
0.08
0.08
0.08
0.08
0.06
0.06
0.17
0.20
0.11
0.18
0.11
0.13
C1–S5
C3–C4
34.60
30.54
17.27
26.30
27.39
15.15
5.70
–
C9–C11
1.99
–
p*
–
–
–
–
N15–C16
–
C12–O13
–
1.95
1.98
1.98
1.98
1.97
–
C9–C11
C12–O14
C9–C11
O14–N15
C16–C17
p*
–
C11–C12
C12–C11
C12–O14
p*
r*
–
8.77
5.49
O
–
14–N15
5.40
C12–C13
–
4.73
C16–N15
C17–H19
C17–H8
1.99
1.99
1.99
1.87
–
O14–N15
N15–C16
N15–C16
C11–C12
–
5.51
p*
–
4.97
4.95
LP(2) O13
r*
–
32.14
50.63
23.35
60.77
30.61
40.66
–
C
12–O14
N15–C16
12–C13
LP(2) O14
1.83
–
p*
–
–
C
LP(2) S5
1.73
–
C3–C4
C1–C2
–
–
–
a
E(2) is the energy of hyper-conjugative interactions (stabilization energy)
Energy difference between donor and acceptor i and j NBO orbitals
F(i, j) is the Fock matrix element between the i and j NBO orbitals
b
c
of 23.35 and 60.77 kcal mol-1. The increased electron density on the oxygen atoms
leads to elongation of the respective bonds and reduction of the corresponding
stretching wavenumber. The intramolecular interaction is a result of orbital overlap
between the p(C–C) and p*(C–C) bond orbitals, which results in ICT and
stabilization of the system. These interactions are observed as an increase in
electron density (ED) in the C–C, C–N, and C–O antibonding orbitals, which
weakens the respective bonds. The electron density (ED) is transferred from the
n(O) to the antibonding p* orbital of the C–C, C–O, and N–C bonds, explaining
both the elongation and the red shift [49].
Charge distribution
The Mulliken [50] atomic charge distribution of the MTISO is shown in Fig. 6.
Mulliken atomic charges were computed by use of the DFT/B3LYP method with
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
Fig. 6 Comparative Mulliken’s plot at the B3LYP/6-311??G(d,p) and B3LYP/6-311??G(2d,p) levels
for MTISO
the 6-311??G(d,p) and 6-311??G(2d,p) basis sets. Calculation of atomic charges
is important in the application of quantum mechanical calculations to molecular
systems [51]. The charge distribution of MTISO shows that carbon atoms attached
to hydrogen atoms are negative whereas other carbon atoms are positively charged.
The oxygen atoms are more negative, and all the hydrogen atoms have positive
charges. This results in positive charges on C3, C4, C12, H6, H7, H8, H10, H18, H19,
and H20, which shows the direction of delocalization and that the natural atomic
charges are more sensitive than Mulliken’s net charges to changes in the molecular
structure. Negatively charged lone pairs on the S5, O13, O14, and N15 atoms show
that charge is transferred from S, O, and N to C (O13, O14 ? C12, N15 ? C16, and
S5 ? C4).
The charge changes with basis set as a result of polarization. For example, the
charges on the H6 and H7 atoms are 0.248 e and 0.73 e at the B3LYP/6-
311??G(d,p) level and 0.192 e and 0.149 e at the B3LYP/6-311??G(2d,p) level.
The charge distribution on the C9 and C11 atoms is increased at the levels of the
6-311??G(d,p) and 6-311??G(2d,p) basis set whereas the opposite trend is
observed for the C3 atom. Considering all the basis sets and the levels used for
atomic charge calculation, the oxygen, nitrogen, and sulfur atoms have substantial
negative charges, and are donor atoms. The hydrogen atoms are positively charged,
and are acceptor atoms.
NMR spectral studies
1
The H and 13C NMR spectra of MTISO are shown in Figs. 7 and 8, respectively.
The 1H NMR and 13C NMR experimental chemical shifts, isotropic shielding
123

H. Kiyani et al.
Fig. 7 Experimental 1H NMR spectrum of MTISO
constants, and spectral assignments are listed in Table 6. The atoms are numbered in
accordance with Fig. 1.
Aromatic carbon atoms give signals in overlapped areas of the spectrum, with
chemical shifts from 100 to 200 ppm [52]. The signals from the eight aromatic
carbon atoms are in the range 114.58–168.69 ppm.
The O and N atoms are highly electronegative and reduce the electron density on
carbon atoms of the isoxazole ring. The chemical shifts of C12 and C16 are thus
attributed to the downfield NMR signals at 177.69 and 170.75 ppm, respectively.
Carbon atoms C2, C9, C3, C4, and C1 are observed up-field, with chemical shifts of
128.92, 136.46, 139.22, 139.59, and 141.52 ppm, respectively; this indicates the
effect of the electronegative sulfur atom is negligibly small, because their signals
are observed in the normal range. Normally, the proton chemical shift of organic
molecules varies substantially with the electronic environment of the proton.
Shielding of hydrogen atoms attached to or near electron-withdrawing atoms or
groups is reduced, moving the resonance to higher frequency, whereas electron-
donating atoms or groups increase shielding and move the resonance to lower
frequency [53]. The chemical shifts of aromatic protons of organic compounds are
usually observed in the range 7.00–8.00 ppm, whereas aliphatic protons resonate at
high field. The signals of the four aromatic protons (1H) are observed at
7.29–8.12 ppm. We predicted H8 at 8.12 ppm in the lowest field of the aromatic
region, and H7 at 7.29 ppm in the highest field of this region. The aliphatic protons
were observed at 2.32 ppm.
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
Fig. 8 Experimental 13C NMR spectrum of MTISO
Molecular electrostatic potential (MEP) surface
To investigate the chemical reactivity of the molecule, the molecular electrostatic
potential (MEP) surface was plotted over the optimized electronic structure of
MTISO by using the density functional B3LYP level with the 6-311??G(2d,p)
basis set. The MEP surface is related to electron density and is a very useful aid to
understanding sites of electrophilic and nucleophilic reactions and hydrogen-
bonding interactions [54]. Figure 9 shows the computationally observed MEP
surface map, with point charges fitted to the electrostatic potential V(r).
123

H. Kiyani et al.
Table 6 Experimental 1H and
13C isotropic chemical shifts
(relative to TMS, all values in
ppm) for MTISO
Assignment
Expt. (d)
Assignment
Expt. (d)
a
H(methyl)
2.315
7.291
7.646
7.957
8.124
C17
C11
C2
11.48
114.58
128.92
136.46
139.22
139.59
141.52
160.67
168.69
H7
H10
H6
H8
C9
C3
C4
C1
C16
C12
a
Mean value
The negative (red) regions of the MEP were related to electrophilic reactivity and
the positive (blue) regions to nucleophilic reactivity. In Fig. 9, this molecule has
several possible sites for electrophilic attack on the nitrogen and oxygen atoms (O13,
O14, and N15). The average maximum negative electrostatic potential value for these
electrophilic sites, calculated at the B3LYP/6-311??G(2d,p) level, are approxi-
mately -22.377 a.u. The point charges fitted to these electrostatic potentials are
-0.568 (O13), -0.215 (O14), and -0.384 (N15). Regions of maximum positive
charge are located on the hydrogen atoms, indicating possible sites for nucleophilic
attack. The MEP map shows that the negative potential sites are on electronegative
atoms and the positive potential sites are around the hydrogen atoms. The MEP
provides a visual representation of the chemically active sites and comparative
reactivity of the atoms.
-6.157e-2
6.157e-2
Charges Electric Potential
(e)
(a.u)
C1
C2
C3
C4
S5
H6
H7
H8
-0.143
-0.220
-0.106
0.066
-0.001
0.201
0.173
0.224
-0.157
0.186
-0.248
0.745
-0.568
-0.215
-0.384
0.505
-0.479
0.132
0.133
0.173
-14.719
-14.748
-14.750
-14.713
-59.188
-1.054
-1.076
-1.085
-14.711
-1.062
-14.735
-14.642
-22.377
-22.307
-18.356
-14.718
-14.750
-1.087
C9
H10
C11
C12
O13
O14
N15
C16
C17
H18
H19
H20
-1.087
-1.076
Fig. 9 Molecular electrostatic potential surfaces (left) and the point charges and electric potential values
(right) on the atoms of MTISO
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
Fig. 10 Calculated TDOS diagrams for MTISO
HOMO–LUMO band gap
Gauss-Sum 2.2 software [55] was used to calculate group contributions to the
molecular orbitals (HOMO and LUMO) and prepare the density of the state (DOS),
shown in Fig. 10. The DOS spectra were created by convoluting the molecular
orbital information with Gaussian cures of unit height.
The energy gap between the HOMO and the LUMO is a critical property
determining molecular electrical transport behavior [56]. Conjugated molecules are
characterized by HOMO–LUMO separation which is the result of substantial ICT
from the end-capping electron-donor groups to the efficient electron-acceptor
groups through a p-conjugated path. Therefore, ED transfer occurs from the more
aromatic part of the p-conjugated system at the electron-donor side to its electron-
withdrawing part. The HOMO, HOMO-1 (An orbital below the HOMO orbital),
LUMO, and LUMO?1 (An orbital above the LUMO orbital) are shown in Fig. 11.
The energy of the HOMO is directly related to the ionization potential, and the
energy of the LUMO is related to the electron affinity. The HOMO–LUMO energy
gap explains charge transfer interactions within the molecule. The frontier orbital
gap for MTISO, obtained by use of the TD-DFT method with the 6-311??G(2d,p)
basis set, is found to be 3.5784 eV. Excitation of intramolecular electron
displacement occurs from the thiophene group to the isoxazole moiety, with the
thiophene and isoxazole rings acting as electron donors and electron acceptors,
respectively.
123

H. Kiyani et al.
ELUMO+1= –0.8882 ev
ELUMO= –3.1252 ev
ΔE=3.5784 ev
ΔE=6.7488ev
EHOMO= –6.7036 ev
EHOMO-1= –7.6370 ev
Fig. 11 The atomic orbital compositions of the frontier molecular orbital for MTISO
UV–visible spectral analysis
On the basis of a fully optimized ground state structure, electronic spectra were
computed for MTISO in the gas phase and in solution in ethyl acetate and DMSO,
by use of the TD-DFT method [57] and the IEF-PCM model [58], using the B3LYP/
6-311??G(d,p) functional, in an attempt to understand the nature of the electronic
transitions. The positions of experimental and calculated absorption peaks (kmax’s),
vertical excitation energies (E), and oscillator strengths (f) are presented in Table 7.
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
Table 7 Theoretical and experimental absorption wavelengths kmax(nm), excitation energies, E (eV),
and oscillator strengths (f) of MTISO, determined by use of TD-DFT/6-311G??(d, p)
Exp.
Calculated
kabs
(nm)
kmax
(nm)
E (eV)
f
Major contribution
Gas phase
–
294
4.22
0.1738 H-3 ? L (88 %), H-2 ? L (4 %), H ? L
(4 %)
_
301
352
294
4.12
3.53
4.22
0.0237 H-2 ? L (94 %), H-3 ? L (4 %)
0.4239 H ? L (96 %), H-3 ? L (4 %)
_
Ethyl
acetate
310
0.1720 H-3 ? L (89 %), H-2 ? L (3 %), H ? L
(4 %)
300
389
298
319
371
301
351
290
312
359
4.11
3.53
4.28
3.97
3.45
0.0233 H-2 ? L (95 %), H-3 ? L (3 %)
0.4264 H ? L (96 %), H-3 ? L (4 %)
0.1065 H-3 ? L (95 %)
DMSO
0.0219 H-1 ? L (98 %)
0.6193 H ? L (99 %)
UV–visible electronic spectra of 3-methyl-4-thiophen-2-ylmethylene-4H-iso-
xazol-5-one in ethanol, DMSO, 1,4-dioxan, CHCl3, and ethyl acetate were recorded
in the range 200-800 nm. Representative spectra are shown in Fig. 12. A clear red
shift of the absorption maxima was observed when changing from low-polarity to
high-polarity solvents. It is suggested for MTISO that p–p* transitions are more
polar in the excited states than in the ground states. In another study it was
concluded that a spectral red shift in high-polarity solvents was mainly because of
greater reduction of the energy of the excited states than that of the ground states
[59].
Common types of electronic transition in organic compounds are p–p*, n–p*,
and p*(acceptor)–p(donor). The strong band for MTISO in DMSO, attributed to the
p ? p* transition, was observed experimentally at 371 nm and calculated to be at
359 nm. The bands observed at 319 and 298 nm are because of n–p* transitions.
The lowest-energy absorption of MTISO corresponded to the first dipole-allowed
p–p* electronic transition from the HOMO orbital to the LUMO orbital, and could
be attributed to ICT.
Thermal analysis
Thermal analysis of MTISO was performed by use of a Perkin-Elmer simultaneous
thermogravimetric and differential thermal (TG/DT) analyzer. The sample was
scanned in the temperature range 25–750 °C at 25 °/min, and the final temperature
was maintained for 10 min. The thermogravimetric (TG) and differential thermal
gravimetry (DTG) curves are shown in Fig. 13. As the temperature was increased to
200 °C, sample weight decreased slightly as a result of evaporation of water.
Weight loss started at approximately 177 °C. Two major weight losses were
observed above 177 °C. The first, 50 % loss, occurred between 177 and 215 °C. The
123

H. Kiyani et al.
1.0
0.8
0.6
0.4
0.2
0.0
DMSO
EtOH
1,4-Dioxane
CH3Cl
Ethyl acetate
300
350
400
450
500
Wavelengths (nm)
Fig. 12 UV–visible absorption spectra of MTISO in different solvents
major weight loss (65 %) occurred over a large temperature range (215–750 °C), in
which almost all the compound was decomposed into gaseous products (10 %
charred material remaining). In the DTG curve, two peaks were identified at 183 °C
and 389 °C, indicating that weight loss by thermal decomposition occurred in two
steps (Fig. 13b).
Non-linear optical properties
On the basis of the finite-field approach, the non-linear optical properties dipole
moment, polarizability, anisotropy polarizability, and first order hyperpolarizability
of MTISO were calculated at the B3LYP level with the 6-311??G(d, p) and
6-311??G(2d, p) basis sets, for more reliability. The numerical values obtained are
listed in Table 8.
The first hyperpolarizability is a third-rank tensor that can be described by a
3 9 3 9 3 matrix. The 27 components of the 3D matrix can be reduced to 10
components as a result of the Kleinman symmetry [60]. The components of b are
defined as the coefficients in the Taylor series expansion of the energy in the
external electric field. When the electric field is weak and homogeneous, this
expansion becomes:
X
X
X
X
1
2
1
6
1
E ¼ E0 ꢁ
liFi ꢁ
aijFiF j ꢁ
bijkFiF jFk ꢁ
c
ijklFiF jFkFl þ :::
24
j
ij
ij
ijkl
ð2Þ
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
a
100
80
60
40
20
0
0
200
400
600
800
Temperature/°C
3.0
2.5
2.0
1.5
1.0
0.5
0.0
b
0
200
400
600
800
Tempruture/°C
Fig. 13 a TGA and b DTG curves of MTISO
where E0 is the energy of the unperturbed molecule, Fi is the field at the origin, li,
aij, bijk, and cijkl are the components of dipole moment, polarizability, first hyper-
polarizability, and second hyperpolarizability, respectively [61]. The total static
123

H. Kiyani et al.
Table 8 Electric dipole moment l (Debye (D)), mean polarizability atot (910-24 esu), anisotropy
polarizability Da (910-24 esu), and first hyperpolarizability hbi (910-31 esu) for MTISO obtained at the
B3LYP level with the 6-311??G(d,p) and the 6-311??G(2d,p) basis sets
Property
B3LYP
d,pa
Property
B3LYP
d,pa
2d,pb
2d,pb
lx
4.930
4.373
-4.807
4.265
bxxx
bxxy
bxyy
byyy
bxxz
bxyz
byyz
bxzz
byzz
bzzz
hbi
954.174
-927.352
115.508
-37.776
150.991
0.194
ly
127.869
41.906
lz
0.000
0.003
l
6.590
6.426
157.117
0.176
axx
axy
ayy
axz
ayz
azz
atot
Da
-12.239
-1.707
-12.296
0.000
-12.124
1.649
-0.012
-0.059
-110.827
-21.405
0.018
0.263
-12.228
-0.001
-0.002
-12.438
-12.263
2.868
0.286
109.556
-21.452
-0.137
89.007
0.000
-12.480
-12.338
2.964
92.366
dipole moment, mean polarizability (atot), anisotropy polarizability (Da), and
average value of the first hyperpolarizability (hbi) can be calculated by use of the
equations:
ꢀ
ꢁ
1
2
l ¼ l2x þ l2y þ l2z
ð3Þ
ð4Þ
ꢂ
ꢃ
1
atot
¼
axx þ ayy þ azz
3
1
2
h
ꢀ
ꢁi
ꢂ
ꢃ
ꢂ
ꢃ
1
2
2
2
pffiffi
Da ¼
axx ꢁ ayy þ ayy ꢁ azz þðazz ꢁ axxÞ þ 6a2xz þ 6ax2y þ 6ay2z
ð5Þ
2
1
2
h
i
2
2
2
hbi ¼ ðbxxx þ byyy þ bzzzÞ þ ðbyyy þ byzz þ byxxÞ þ ðbzzz þ bzxx þ bzyy
Þ
ð6Þ
It is well known that high values of the dipole moment, molecular polarizability,
and hyperpolarizability are important for more active non-linear optical (NLO)
properties. The calculated dipole moments for MTISO are 6.590 and 6.426 D.
Calculated polarizabilities aij have non-zero and zero values and are dominated
by the diagonal components. Total polarizability (atot) was calculated as
–12.338 9 10-24 and –12.263 9 10-24 esu. The first hyperpolarizability values
(hbi) for MTISO are 9.2366 9 10-31 and 8.9007 9 10-31 esu. Urea a prototypical
molecule used to study the NLO properties of molecular systems. It has, therefore,
frequently been used as a threshold value for comparative purposes. The first
hyperpolarizability for MTISO is 7.11 times the magnitude for the standard NLO
material urea (0.13 9 10-30 esu) [62].
123

Three-component synthesis of a,b-unsaturated isoxazol-5(4H)-ones
Table 9 Thermodynamic properties at different temperatures, at the B3LYP/6-311??G(2d,p) level of
theory, for the MTISO molecule
T (K)
Cpo;m (cal mol-1 K-1
)
Som (cal mol-1 K-1
)
Hmo (kcal mol-1
)
E (kcal mol-1
)
100
150
200
250
298.15
300
350
400
450
500
550
600
650
700
750
800
19.641
25.451
31.521
37.865
43.935
44.180
50.200
55.764
60.804
65.319
69.342
72.926
76.125
78.990
81.641
83.967
73.143
82.209
7.314
12.331
18.071
24.517
31.359
31.661
39.481
47.950
57.033
66.693
76.892
87.596
98.775
110.397
121.697
134.086
90.424
91.452
90.355
92.776
98.070
94.411
105.180
105.535
112.804
119.877
126.742
133.388
139.806
145.997
151.964
157.712
162.265
167.610
96.292
96.364
98.626
101.178
103.996
107.052
110.321
113.781
117.410
121.190
124.959
129.001
Thermodynamic functions
On the basis of vibrational calculation at the B3LYP/6-311??G(2d,p) level of
theory, the standard statistical thermodynamic functions heat capacity (Cp0;m),
entropy (S0m), enthalpy (Hm0 ), and molecular energy (E) for MTISO were obtained
from theoretically calculated frequencies; the results are listed in Table 9.
It is apparent these thermodynamic functions increase with temperature in the
range 100–800 K; this is because molecular vibrational intensities increase with
temperature [63]. The corresponding quadratic equations obtained by use of
B3LYP/6-311??G(d,p) are:
Cp0;m ¼ 3:1871 þ 0:1601T ꢁ 7 ꢂ 10ꢁ5T2 ðR2 ¼ 0:9994Þ
S0m ¼ 55:939 þ 0:1808T ꢁ 5 ꢂ 10ꢁ5T2 ðR2 ¼ 0:9999Þ
ð7Þ
Hm0 ¼ 2:7735 þ 0:0827T ꢁ 1 ꢂ 10ꢁ4T2 ðR2 ¼ 0:9999Þ
E ¼ 88:178 þ 0:014T ꢁ 5 ꢂ 10ꢁ5T2 ðR2 ¼ 0:9996Þ
These equations can be used to compute other thermodynamic quantities,
because of the relationships among thermodynamic functions, and to estimate the
directions of chemical reactions by use of the second law of thermodynamics. All
thermodynamic calculations were performed for the gas phase and cannot be used
for solutions.
The related figure is shown in Fig. 14.
123

H. Kiyani et al.
0
180
160
140
120
100
80
C
p,m
0
m
0
S
H
E
m
60
40
20
0
0
100
200
300
400
500
600
700
800
900
Temperature (K)
Fig. 14 Correlation graph of thermodynamic properties and temperatures for the MTISO molecule,
obtained by use of B3LYP/6-311??G(2d,p)
Reactive descriptors of MTISO
Global reactivity
The energies of the frontier molecular orbitals (EHOMO, ELUMO), energy band gap
(EHOMO - ELUMO), electronic chemical potential (l), electronegativity (v), global
hardness (g), global softness (S), and electrophilicity index (x) [64] of MTISO are
listed in Table 10.
On the basis of EHOMO and ELUMO, these were calculated by use of the equations:
1
l ¼ ðEHOMO þ ELUMO
Þ
ð8Þ
ð9Þ
2
1
v ¼ ꢁl ¼ ꢁ ðEHOMO þ ELUMO
Þ
2
1
g ¼ ðEHOMO ꢁ ELUMO
Þ
ð10Þ
ð11Þ
2
1
S ¼
2g
123