A new series of Schiff bases derived from sulfa drugs and indole-3-carboxaldehyde: Synthesis, characterization, spectral and DFT computational studies

Article abstract of DOI:10.1016/j.molstruc.2013.01.063

A new series of Schiff bases were synthesized for the first time by the condensation of indole-3-carboxaldehyde with various sulfa drugs including sulfanilamide, sulfapyridine, sulfadiazine, sulfamerazine, sulfamethoxazole, sulfamethoxypyridazine and sulf

Full text of DOI:10.1016/j.molstruc.2013.01.063

Accepted Manuscript
A New Series of Schiff Bases Derived from Sulfa Drugs and Indole-3-carbox‐
aldehyde: Synthesis, Characterization, Spectral and DFT Computational Studies
H. Ebrahimi, J.S. Hadi, H.S. Al-Ansari
PII:
S0022-2860(13)00098-7
DOI:
http://dx.doi.org/10.1016/j.molstruc.2013.01.063
MOLSTR 19533
Reference:
To appear in:
Journal of Molecular Structure
Received Date:
Revised Date:
Accepted Date:
8 November 2012
24 January 2013
26 January 2013
Please cite this article as: H. Ebrahimi, J.S. Hadi, H.S. Al-Ansari, A New Series of Schiff Bases Derived from Sulfa
Drugs and Indole-3-carboxaldehyde: Synthesis, Characterization, Spectral and DFT Computational Studies, Journal
of Molecular Structure (2013), doi: http://dx.doi.org/10.1016/j.molstruc.2013.01.063
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A New Series of Schiff Bases Derived from Sulfa Drugs and
Indole-3-carboxaldehyde: Synthesis, Characterization,
Spectral and DFT Computational Studies
H. Ebrahimi1, J. S. Hadi2,*, H. S. Al-Ansari2
1Department of Biochemistry and National Magnetic Resonance Facility at Madison
(NMRFAM), University of Wisconsin-Madison, Madison, WI 53706, USA
2Department of Chemistry, College of Education, University of Basrah, Iraq
Jabbar S. Hadi
Department of Chemistry
University of Basrah
Basrah, Iraq
Tel: (964) 7710822193
*Corresponding Author. E-mail: jshalkabi@yahoo.com
1

ABSTRACT
A new series of Schiff bases were synthesized for the first time by the
condensation of indole-3-carboxaldehyde with various sulfa drugs including
sulfanilamide, sulfapyridine, sulfadiazine, sulfamerazine, sulfamethoxazole,
sulfamethoxypyridazine and sulfacetamide sodium in ethanol (1:1). The structure of
1
Schiff bases were experimentally characterized by using IR, H NMR, 13C NMR and
mass spectroscopic methods. The structural and electronic properties of the studied
molecules were investigated theoretically by performing density functional theory
(DFT) to access reliable results to the experimental values. The molecular geometry,
the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular
orbital (LUMO) and Mulliken atomic charges of the studied molecules have been
calculated at the B3LYP method and standard 6-31+G(d,p) basis set starting from
optimized geometry. The theoretical 13C chemical shift results were also calculated
using the gauge independent atomic orbital (GIAO) approach and their respective
linear correlations were obtained. The comparison of the results indicates that
B3LYP/6-31+G(d,p) yields good agreement with the observed chemical shifts.
Keywords: Schiff base, Sulfa drug, Indole-3-carboxaldehyde, 13C NMR, HOMO,
DFT computational studies
2

1. Introduction
Sulfa drugs are known as the first drugs used as preventive and therapeutic
compounds against several of bacterial infections such as eye infections, influenza,
meningitis and other meningides, actinomices infections, and urinary tract infections
[1-3]. They can also be used as model compounds for investigation of mechanisms of
the action of drugs [4-6]. A large number of Schiff bases derived from sulpha drugs
have been synthesized and used as ligands to prepare potent metal complexes [7-10].
Schiff base compounds have attracted considerable attention in both theoretical and
experimental studies. The remarkable electronic and striking tenability of Schiff bases
make them to be among the most widely used organic compounds. Schiff bases are
applied in many different areas such as catalysts, polymer stabilizers, intermediates in
organic synthesis, and as pigments and dyes [11-13]. In addition, Schiff bases are an
important class of ligands which are most versatile and thoroughly studied ligands in
coordination chemistry. Schiff bases have also been shown to exhibit a broad range of
biological activities, including antifungal, antibacterial, antimalarial, anti-
proliferative, anti-inflammatory, antiviral, and antipyretic properties [14-16].
In addition, heterocyclic compounds such as indole, pyridine, pyrimidine,
pyrazine, and pyridazine as well as related molecules are considered as good ligands
because of presence of one nitrogen atom or more which has a localized pair of
electrons. For instance, Schiff bases of heterocyclic sulfonamides have been
investigated as inhibitors of zinc enzyme carbonic anhydrase as well as management
of multitude of tumors [17-19]. These compounds are used in the synthesis of several
compounds such as antibiotics, antiallergics, antiphlogistics and antitumor substances
[20-22]. The classical synthesis of this important class of compounds goes back to
Schiff’s report which has involved the condensation of a carbonyl compound with an
3

amine under azeotropic distillation [23]. The condensation products of sulfa drugs
with aldehydes, ketones or their derivatives are very active biologically, besides
having good complex ability [24].
Also, prediction of molecular properties of polyatomic molecules by quantum
mechanical methods has become important because of its accurate and consistent with
experimental data. By increasing development of computational chemistry, density
functional theory (DFT) has been extensively used to calculate a wide variety of
molecular properties and provided reliable results which are in accordance with
experimental data [25, 26].
In connection of widely applications for this major class of compounds, for the
first time, we have synthesized and characterized a new series of Schiff bases derived
from sulfa drugs and indole-3-carboxaldehyde. Also, these new synthesized
compounds have been characterized on the basis of spectroscopic methods including
1
IR, H and 13C NMR as well as mass spectroscopy. To additionally verify the
proposed assignments, quantum chemical calculations have been performed. In the
present study, we have also extended the probing into the application of DFT
methods. Therefore, these synthesized compounds have theoretically investigated by
using the more popular DFT methods, B3LYP, in 6-31+G(d,p) basis set. In order to
make sense between the experimental and theoretical results, the electronic properties
such as HOMO-LUMO energies, and Mulliken atomic charges were calculated and
the results were discussed.
2. Experimental procedure
2.1. Materials
4

All of the chemicals and solvents employed in synthesis were of extra-pure
grade and used as received without further purification. Sulfanilamide, sulfapyridine,
sulfadiazine, sulfamerazine, sulfamethoxazole, sulfamethoxypyridazine and
sulfacetamide sodium as well as indole-3-carboxaldehyde were obtained from Fluka
and Himedia. The organic solvents used included absolute ethanol and ethyl acetate
were obtained from BDH and Riedel-de haen.
2.2. Instrumentation and spectral measurements
IR spectra were recorded by using Shimadzu FTIR-8300 spectrophotometer in
the region 4000-200 cm−1 in KBr pellet and in CCl4 solution. The spectra were
1
collected with a resolution of 2 cm−1 with 15 scans. The experimental values of H
13
and C NMR as well as DEPT-135 spectra for the studied compounds were scanned
on a Bruker Avance DX500 MHz spectrometer with a field gradient operating at
500.13 MHz for proton observation. TMS as the internal standard was used as
referenced to 0.0 ppm. DMSO-d6, D2O, CD3OD were used as solvents. The
experiments were run in unlock mode, with sufficient a number of scans to achieve
S/N ratios 200:1 (ca.). NMR spectra were obtained at a probe temperature of about
298 K. Melting points were determined using a BUCHI 510 apparatus in open
capillaries and were left uncorrected. The mass spectra were scanned by the EI
technique at 70 eV with an Agilent Technologies 5975C spectrometer.
2.3. Synthesis of Schiff Base Compounds
2.3.1. Preparation of ISN, ISD, ISM, ISMT, ISMP, ISPY and ISA
The title compounds were synthesized in a general procedure by the
condensation of Indole-3-carboxaldehyde with sulfanilamide, sulfadiazine,
5

sulfamerazine, sulfamethoxazole, sulfamethoxypyridazine, sulfapyridine and
sulfacetamide sodium, respectively, in ethanol (1:1). The synthesis of Schiff bases
were performed in accordance with reaction Scheme 1. The reaction mixture was
refluxed for half to three hours and allowed to cool, filtered and the products
recrystallized by appropriate solvent. The purity of the products and composition of
the reaction mixture were monitored by thin layer chromatography using chloroform:
ethanol (9:1) or ethyl acetate: benzene (3:7). The structures of synthesized Schiff
bases with related sulfa drugs are shown in Table 1. Also, the observed physical
properties of title compounds are given in Table 2.
3. Computational aspects
In present work, a non-local DFT method, B3LYP, was used to perform
theoretical calculations on the studied compounds. The DFT methods are more
advantageous owing to their accuracy and low computational cost. These properties
make DFT more practical and feasible for the computations of different molecules
[27-30]. As the more popular DFT methods, B3LYP is consistently one of the best
performing DFT methods. The geometry of all compounds was fully optimized at the
B3LYP level of theory along with standard 6-311+G(d,p) basis set which has amply
been proven to give very good ground-state geometries. Vibrational frequency
analyzes, calculated at the same level of theory, indicate that the optimized structures
are at the stationary points corresponding to local minima without any imaginary
frequency. The electronic properties were calculated using B3LYP method based on
the optimized structures. In addition, a comparison was made between the
theoretically calculated 13C chemical shift constants and the experimentally measured
13C chemical shifts. GIAO (Gauge Including Atomic Orbital) as the most widely used
6

approach for calculating NMR shielding tensors were applied [31-35]. The Gaussian
09 package was employed to perform optimization of structures and all the
calculations [36].
4. Results and discussion
4.1. Experimental results
In this section, spectral studies including the observed spectroscopic results for
the title compounds are discussed.
4.1.1. IR spectra analysis
The infrared spectral data of the studied compounds are listed in Table 3. IR
spectra of compounds showed a strong band at 1653–1636cm-1 that attributed to
azomethine ν(CH=N). The absence of band ~1720 and 3300 cm-1 due to carbonyl
stretching and NH2 stretching respectively indicates the condensation of indole-3-
carboxaldehyde and sulfa drugs in 1:1 mole ratio. The high value of ν(CH=N)
stretching in these compounds when compared with that derived from another
aromatic aldehyde (substituted benzaldehyde, naphthaldehyde, etc.) can be explained
by a strain of indole moiety. All IR spectra of compounds show a first strong band
within the range 1376–1228cm-1 which attributed to asymmetric stretching of
(O=S=O) and the second within the range 1163–1136 assigned to symmetric
stretching of (O=S=O) [37].
4.1.2. Mass spectra analysis
All compounds show a molecular ion (M.+) with low relative intensity except
ISN (40%). The molecular ion peaks are in agreement with proposed empirical
formulas. The loss of 64 units (SO2 group) generates an intense peak in most
7

compounds spectra where this peak represents the base peak. The possible suggested
ion fragments as the result of fragmentation of the ISN is given in Scheme 2. The
important fragments and their intensity for the other molecules are given in Table 4.
4.1.3. 1H and 13C NMR spectra analysis
1H NMR spectra recorded in different solvents namely in DMSO-d6 as well as
DMSO-d6 + D2O or in CD3OD. The 1H NMR spectrum of ISM with and without D2O
is presented in Fig. 1. The spectra of all compounds show the azomethine proton
(CH=N) as singlet signal at δ ~ 9.86–9.93 ppm in all solvents. The 1H NMR spectra of
ISN, ISM, and ISMT display the NH of indole moiety as singlet signal at ~12 (in
DMSO-d6), while the signal cannot be seen in their spectra due to deuterium exchange
in DMSO-d6+D2O. The signal of NH proton in sulfa moiety appears as singlet at ~6
ppm in case of compounds ISM and ISMT disappear after addition of D2O (Fig. 1).
As expected, the NH proton of sulfa moiety shows different chemical shifts when the
spectra recorded in CD3OD where the signal appears at ~8.3 as a broad signal in
ISMP and ISA compounds. The chemical shifts of different types of protons in all
compounds are listed in Table 5.
The 13C NMR spectra and DEPT-135 of compounds were recorded in DMSO-
d6. All spectra exhibited signals from azomethine carbon at δ=184 ppm as the highest
chemical shift in our synthesized Schiff bases. All quaternary carbon atom signals
disappear in DEPT-135. The measured chemical shifts of all carbon atoms for ISN,
ISM and ISMT are listed in Table 6, where the numbering of the carbon atoms is
presented only for 13C NMR data assignment in Fig. 2. Also, magnetically equivalent
carbons are displayed by same number.
4.2. Computational results
8

As mentioned above, all calculation carried out in B3LYP method in 6-
31+G(d,p) basis set. The results are discussed for ISMT as a case study and results
for other Schiff bases are given in supplementary data. The optimized structure of
ISMT along with labeling of atoms is shown in Fig. 3. The figure shows the molecule
in the ball and stick model. The geometry optimization yields non planar structure.
Also, the most optimized structural parameters of ISMT calculated by B3LYP/6-
311+G(d,p) are presented in Table 7.
4.2.1. Electronic properties
The most important orbitals in a molecule are the frontier molecular orbitals,
called HOMO (the highest occupied molecular orbital) and LUMO (the lowest-lying
unoccupied molecular orbitals). The HOMO represents the ability to donate an
electron, LUMO as an electron acceptor represents the ability to obtain an electron.
These orbitals play an important role in the electric properties and determine the way
the molecule interacts with other species [38-40]. Both the HOMO and the LUMO are
the main orbital taking part in chemical reaction. While the energy of the HOMO is
directly related to the ionization potential, LUMO energy is directly related to the
electron affinity. Also, the frontier orbital gap, the energy gap between HOMO and
LUMO, represents stability of structures and helps to characterize some significant
issues including the kinetic stability as well as chemical reactivity of the molecule
[41]. A molecule with a small frontier orbital gap is more polarizable and is generally
associated with a high chemical reactivity as well as low kinetic stability [42]. The
conjugated molecules are characterized by a small highest occupied molecular orbital-
lowest unoccupied molecular orbital (HOMO-LUMO) separation.
9

In order to evaluate the energetic behavior of the title compounds, we carried
out calculations for ISMT. The HOMO and LUMO energy calculated by B3LYP
method in 6-31+G(d,p) basis set is presented in Table 8. The plots of frontier
molecular orbitals for ISMT are shown in Fig. 4. It is clear from the figure that, while
the HOMO is localized on whole the indole and almost the benzene ring, the LUMO
is localized mainly on the indole, the benzene ring and oxygen atoms in sulfonyl
group. These orbitals significantly overlap in their position over the indole ring. The
frontier energy gap implies an electron density transfer to the benzene ring from the
indole ring and also explains the eventual charge transfer occurs within the
compound. According to calculation, the energy band gap of ISMT reveals about -
0.37 a.u. by B3LYP method at the mentioned basis set. The detail result in B3LYP is
HOMO energy = -0.293 a.u.
LUMO energy = 0.078 a.u.
HOMO-LUMO energy gap = -0.37 a.u.
This small energy gap confirms the conjugated compound with high chemical
reactivity as well as high polarizability.
4.2.2. Mulliken population analysis
The Mulliken analysis is the most common population analysis method.
Mulliken atomic charge calculation has a significant role in the application of
quantum chemical calculations to molecular systems because of atomic charges affect
some properties of molecular systems including dipole moment, and molecular
polarizability. It also has been used to describe the electrostatic potential surfaces [43-
45]. The total atomic charge values of ISMT obtained by Mulliken population
10

analysis [46] in the applied method are listed in Table 9. The charge changes with
methods presumably occur due to variation of the hybrid functionals. Illustration of
atomic charges plotted is shown in Fig. 5. As can be seen in Table 9 and Fig. 5, all the
hydrogen atoms have a net positive charge. The obtained atomic charge shows that
the H5 atom has bigger positive atomic charge (0.3384e) than the other hydrogen
atoms. This is due to the presence of electronegative nitrogen atom (N4), the
hydrogen atom (H5) attracts the positive charge from the nitrogen atom (N4).
Moreover, Mulliken atomic charges also confirm that an H38 atom in indole ring is
more acidic due to more positive charge. As expected, the results show that the charge
of the nitrogen atom (N26) in imine group and the charge of the nitrogen atom in
indole ring, the charge of N43, are negative. Considering the applied method used in
the atomic charge calculation, the oxygen atoms in sulfonyl group exhibit a negative
charge, which are donor atoms.
4.2.3. NMR analysis
In order to comparison between experimental and theoretical NMR data,
which may be helpful in making correct assignments and understanding the
relationship between chemical shift and molecular structure, 13C NMR chemical shifts
calculation for further clarification of synthesized molecules are reported. To clarify
the relation between theoretical and experimental values of NMR chemical shift
constants, the experimental data are plotted versus computed values.
The 13C NMR chemical shifts of all carbons were calculated on the optimized
structures of compounds using B3LYP method employing 6-31+G(d,p) basis set for
all atoms. The impact of the solvent was taken into account using the Polarized
Continuum Model (PCM) of Tomasi et al. [47]. In order to compute the 13C NMR
chemical shifts, each couple of carbon atoms on equivalent locations of the molecule
11

were considered as equivalent and their average of chemical shifts were calculated.
The isotropic 13C chemical shifts for other compounds are given in supplementary
data and compared with the experimental values. The statistical parameters of
13
computed C NMR chemical shifts at the B3LYP/6-31+G(d,p) level of theory along
with experimental data for ISN, ISM, and ISMT compounds are given in Table 10.
As can be seen, the results obtained by using this method are in reasonable agreement
with experimental values. The results are close to experimental data and they differ
slightly from results of experiment. As shown in Fig. 6, there is a good linear
relationship between experimental and theoretical B3LYP/6-31+G(d,p) chemical
shifts. Similar plots for other calculated NMR results are given in supplementary
content.
5. Conclusion
The synthesis, characterization, and theoretical study of several new Schiff
bases derived from condensation of sulfa drugs and Indole-3-carboxaldehyde were
reported. Spectroscopic techniques including IR, 1H and 13C NMR, and mass analysis
were used to identify the products. To study the structural and electronic properties of
studied molecules, complete analyses of the 13C NMR spectra, HOMO-LUMO energy
gap as well as the Mulliken atomic charges of title compounds was reported. All
theoretical calculations were carried out by the more popular DFT methods, B3LYP,
at 6-31+G(d,p) level of theory. The applied method is in good accordance with
experimental values. The HOMO-LUMO energy gap as an important value for
stability index revealed high chemical reactivity of synthesized compounds in
chemical reactions.
Supplementary data
12

Supplementary data contains a complete set of experimental and theoretical
13C chemical shifts with related plots.
13

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17

Table 1. Structures of synthesized Schiff bases with related sulfa drugs
Schiff base structure
Sulfa drug
Schiff base
Sulfanilamide
ISN
Sulfadiazine
Sulfamerazine
ISD
ISM
Sulfamethoxazole
Sulfamethoxypyridazine
ISMT
ISMP
Sulfapyridine
ISPY
ISA
Sulfacetamide sodium
18

Table 2. Physical properties of studied compounds
Yield %
Reaction Solvent of
Color, melting
MW,
Physical
state
Molecular
Formula
Compound
time
Recrystallization point (°C)
(min)
40
80
44
21
30
120
90
Ethanol
Ethanol
Ethanol
Water: Ethanol
1:1
O (224-227)
O-Y (218-220) 377.3 (c)
O-Y (162-164) 391.4 (c)
299.2 (s)
C15H13N3O2S
C19H15N5O2S
C20H17N5O2S
C19H16N4O3S
ISN
ISD
ISM
ISMT
120
O (178-180)
380.4 (s)
37
35
20
120
Ethanol
Dichloro-
methane
Ethanol
Y (236-238)
Y (147-150)
407.4 (c)
376.4 (s)
C20H17N5O3S
C20H16N4O2S
ISMP
ISPY
72
60
Y (168-170)
363.3 (s)
C17H14N3NaO3S ISA
s: Solid, c: Crystal, O: Orange, O-Y: Orange-Yellowish, Y: Yellow
19

Table 3. IR spectral data with vibrational assignment of the studied compounds
Bond
Compound
ISN
N-H
C=C
C-H
Sp2
C=N
O=S=O
Other
Sulfa
Aromatic Azomethine
Sp3
Azomethine Asya/Symb
Indole 3-Aldehyde
3240
3252
3171
3171
3210
3240
3286
3477Asy
3418Sym
3348
1500
1493
1445
1447
1491
1447
1491
2925
2934
2928
2976
2922
2930
2983
3100 Asy
3050 Sym
3109 Asy
3078 Sym
3107 Asy 2860 Asy
3043 Sym 2820 Sym
3105 Asy 2930 Asy
3042 Sym 2900 Sym
3188 Asy 2858 Asy
3096 Sym 2818 Sym
__
1649
1653
1636
1636
1653
1636
1649
1342 Asy
1155 Sym
1338 Asy
1153 Sym
1331 Asy 1518(m) (NH bend)
1 148 Sym
1387 Asy 1524(m) (NH bend)
1128 Sym
1342 Asy
1128 Sym
1558(s) (NH bend)
1585(s) (NH bend)
ISD
__
ISM
3385
3456
3448
3369
__
ISMT
ISMP
ISPY
ISA
1579(s) (NH bend)
3103 Asy
3043 Sym
3150 Asy 2930 Asy
3067Sym 2856 Sym
__
1387 Asy 1518(m) (NH bend)
1132 Sym
1336 Asy
1709 (C=O)
1155 Sym 1583(s) (NH bend)
a Asymmetry, b Symmetry
20

Table 4. The mass spectra data of the studied compounds
Compound
m/z (%)
M.+ 299.1 (40), [M-SO2] .+ 235 (8), 219 (18),
172 (97), 156 (base peak), 143 (10), 116 (11).
M.+ 377 (1), [M-SO2] .+ 313 (6), 185 (base peak),
156 (3), 108 (18), 92 (35).
ISN
ISD
M.+ 391 (3), 299 (8), 199 (43), 146 (80),
144 (base peak), 116 (39), 89 (33).
ISM
ISMP
ISPY
ISA
M.+ 409 (3), [M-SO2] .+ 343 (15), 339 (20), 312 (5),
245 (35), 215 (12), 171 (base peak), 115(13), 92 (8).
M.+ 377 (1), 312 (8), 184 (base peak), 170 (3), 153 (6),
108 (19), 92 (41), 85 (29).
M.+ 363 (3), 348 (4), 320 (4), 299 (base peak), 265 (9), 235(16),
208 (46), 156 (49), 108 (51), 92 (66), 83 (69).
21

Table 5. 1H NMR chemical shifts (in ppm)
OCH3 SO2NH2 Methyl CH=N
(Indole moiety)
NH H (aromatic)
(Sulfa moiety) (Ar–H)
Compound
---
---
---
---
3.9
---
---
6.9
---
---
---
---
---
---
---
---
2.3
1.05
---
9.93
9.32
9.93
9.86
9.87
9.86
9.90
12.1 (s)
12.31 (s)
12.0 (s)
12.2 (s)
9.4 (br)
8.1 (br)
8.3 (br)
---
6.6-8.59, 9H (m) ISN
7.0-8.48, 12H (m) ISD
6.7-8.3, 10H (m) ISM
7.2-8.2, 10H (m) ISMT
6.6-8.1, 11H (m) ISMP
6.6-8.4, 13H (m) ISPY
8.2 (br)
6.0 (s)
6.0 (s)
8.35 (br)
6.9 (br)
---
1.92
7.2-8.7, 9H (m)
ISA
s: singlet, d: doublet, m: multiplet, br: broad
22

Table 6. 13C chemical shifts (in ppm) for ISN, ISM and ISMT
ISMT
Exp.
ISM
Exp.
ISN
Exp.
DEPT
185.4
---
DEPT
185.4
---
DEPTb
185.4
---
Carbona
185.4
118.6
124.6
123.9
122.6
123.9
121.2
130.3
138.9
151.9
112.8
126.5
137.5
151.9
170.3
12.5
185.4
118.6
124.6
123.9
122.6
123.9
121.3
130.5
138.9
153.4
112.8
130.5
137.5
157.4
138.9
121.3
153.4
185.4
118.6
124.5
123.9
122.6
123.9
121.3
130.5
138.9
152.3
112.9
127.9
137.5
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
---
---
---
123.9
122.6
123.9
121.2
---
138.9
---
112.8
126.5
---
123.9
122.6
123.9
121.3
---
138.9
---
112.8
130.5
---
123.9
122.6
123.9
121.3
---
138.9
---
112.9
127.9
---
---
---
12.5
97.6
---
138.9
121.3
---
97.6
a Labeling numbers are given in Fig. 2.
bDEPT: Distortionless Enhancement by Polarization Transfer spectrum
23

Table 7. Optimized geometrical parameters of ISMT calculated by B3LYP/6-311+G(d,p)
Value (o) Dihedral angle Value (o) Bond angle
Value (Å) Bond length
170.0
-49.8
-159.0
22.3
39.8
179.9
-23.8
O2–S1–N4–H5
O2–S1–N4–C6
O2–S1–C16–C17
O2–S1–C16–C18
O3–S1–N4–H5
O3–S1–N4–C6
O3–S1–C16–C17
O3–S1–C16–C18
N4–C6–N11–O8
H5–N4–C6–N11
O8–C9–C7–H10
122.7
105.8
103.3
111.4
122.7
113.7
103.3
127.4
104.7
109.7
109.4
O2–S1–O3
O2–S1–N4
O3–S1–N4
H5–N4–S1
C6–N4–S1
C6–N4–H5
C6–C7–C9
C6–C7–H10
C6–N11–O8
C7–C9–O8
C9–O8–N11
C9–C12–H13
C9–C12–H14
C9–C12–H15
1.464
1.463
1.708
1.788
1.017
1.398
1.426
1.317
1.363
1.077
1.353
1.488
1.115
1.095
S1–O2
S1–O3
S1–N4
S1–C16
N4–H5
N4–C6
C6–C7
C6–N11
C7–C9
157.5
-175.2
2.986
178.7
-1.319
0.064
179.3
-178.5
0.045
-179.0
-179.2
-0.161
-178.7
177.4
-2.274
177.7
-179.9
-0.078
179.9
178.9
179.1
179.9
-179.9
0.019
0.021
-0.019
0.014
-0.025
-179.9
-0.015
0.017
0.096
-0.007
-0.004
C7–H10
C9–O8
C16–C17–C19–C23 110.7
C16–C18–C21–C23 110.8
C17–C19–C23–N26 110.0
C18–C21–C23–N26 107.7
C19–C17–C16–C18 108.6
H20–C17–C16–C18 108.7
H24–C19–C23–C21 108.1
H25–C21–C23–N26 108.3
H25–C27–H28–C29 119.9
N26–C23–C19–C21 120.1
N26–C27–C29–C30 120.7
N26–C27–C29–C31 120.6
C27–C29–C30–C32 119.7
C27–C29–C30–C33 120.9
C27–C29–C31–N43 123.3
H28–C27–C29–C30 106.7
H28–C27–C29–C31 109.7
C29–C30–C32–C35 106.4
C29–C30–C33–C36 122.6
C29–C30–C32–N43 107.3
C29–C31–N43–C32 109.5
C30–C32–C35–C39 125.0
C30–C33–C36–C39 117.1
C31–N43–C32–C30 121.3
C31–N43–C32–C35 120.9
C32–C35–C39–C36 129.9
C33–C36–C39–C35 121.1
H34–C31–N43–H38 119.3
H37–C33–C36–H41 119.4
H42–C39–C35–H40 119.1
C9–C12
N11–O8
C12–H13
C12–H14
C12–H15
C16–C17
C16–C18
C17–C19
C17–H20
C18–C21
C18–H22
C19–C23
C19–H24
C21–C23
C21–H25
C23–N26
C27–N26
C27–H28
C27–C29
C30–C29
C30–C32
C30–C33
C31–H34
C31–N43
C32–C35
C33–C36
C35–C39
C36–C39
N43–C32
N43–H38
H13–C12–H14 1.095
H13–C12–H15 1.091
H14–C12–H15 1.401
C16–S1–O2
C16–S1–O3
1.397
1.389
C16–C17–H20 1.084
C16–C18–H22 1.392
C17–C19–C23 1.084
C18–C21–C23 1.409
C23–N26–C27 1.085
N26–C27–H28 1.409
N26–C27–C29 1.085
C29–C30–C32 1.398
C29–C31–N43 1.289
C30–C29–C31 1.100
C30–C32–C35 1.440
C30–C32–N43 1.450
C31–N43–C32 1.418
C31–N43–H38 1.405
C32–C35–C39 1.081
C33–C36–C39 1.367
H34–C31–N43 1.397
C35–C32–N43 1.392
C35–C39–C36 1.392
C35–C39–H42 1.410
C36–C39–H42 1.390
C39–C36–H41 1.008
24

Table 8. HOMO-LUMO energy values of ISMT
Energy (a.u.)
-0.2929
HOMO
-0.0778
LUMO
-0.3707
HOMO-LUMO energy gap
25

Table 9. Mulliken atomic charge of ISMT
Charge
0.1475
0.0490
-0.3341
0.1603
0.3064
-0.2513
0.1205
0.1263
0.1251
-0.3049
Atom
34 H
35 C
36 C
37 H
38 H
39 C
40 H
41 H
42 H
43 N
Charge
-0.5799
0.1385
0.1254
-0.0584
0.2638
0.1073
0.5177
0.9662
-0.2698
-0.9877
-0.5304
Atom
23 C
24 H
25 H
26 N
27 C
28 H
29 C
30 C
31 C
32 C
33 C
Charge
-0.6963
0.1798
0.1781
0.1662
-1.0815
0.2130
0.4499
0.6644
0.1604
-0.6270
0.1468
Atom
12 C
13 H
14 H
15 H
16 C
17 C
18 C
19 C
20 H
21 C
22 H
Charge
1.4039
-0.5074
-0.4954
-0.4786
0.3384
-0.3309
0.6140
-0.0035
0.0279
0.1652
-0.3253
Atom
1 S
2 O
3 O
4 N
5 H
6 C
7 C
8 O
9 C
10 H
11 N
26

Table 10. Statistical parameters of experimental vs. theoretical 13C chemical shifts
Correlation
0.9981
0.9985
Intercept
-3.540
-2.215
-2.333
Slope
1.056
1.051
1.042
Method
ISN
ISM
0.9993
ISMT
27

Figure Caption
Scheme 1. Preparation procedure of Schiff bases with general structure
Scheme 2. Suggested mass fragmentation of ISN
Fig. 1. 1H NMR spectra of ISM
Fig. 2. Structure of ISN, ISM and ISMT with the numbering of the carbon atoms
(which is only for 13C NMR data assignments in Table 6)
Fig. 3. The optimized structure of ISMT within numbering of atoms obtained at
B3LYP/6-311+G(d,p) level of theory.
Fig. 4. The atomic orbital compositions of the frontier molecular orbital of ISMT
Fig. 5. The Mulliken atomic charge distribution of ISMT
Fig. 6. Experimental values vs. theoretical 13C NMR chemical shifts of ISMT
28

Scheme 1. Preparation procedure of Schiff bases with general structure
29