Efficient ZrO(NO3)2.2H2O Catalyzed Synthesis of 1 H -Indazolo[1,2- b ] phthalazine-1,6,11(13 H)-triones and Electronic Properties Analyses, Vibrational Frequencies, NMR Chemical Shift Analysis, MEP: A DFT Study

Article abstract of DOI:10.1155/2020/9483520

The synthesis of 1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione derivatives, using one-pot three-component condensation reaction of 3-nitrophthalic anhydride, hydrazine monohydrate, dimedone, and aromatic aldehydes in the presence of ZrO(NO₃)₂.2H₂O as the novel catalyst and in reflux conditions in EtOH was reported. Quantum theoretical calculations for three structures of compounds (5a, 5b, and 5c) were performed using the Hartree-Fock (HF) and density functional theory (DFT). From the optimized structure, geometric parameters were obtained and experimental measurements were compared with the calculated data. The structures of the products were confirmed by IR, ¹H NMR, ¹³C NMR, mass spectra, and elemental analyses. The IR spectra data and ¹H NMR and ¹³C NMR chemical shift computations of the 1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione derivatives in the ground state were calculated. Frontier molecular orbitals (FMOs), total density of states (DOS), thermodynamic parameters, and molecular electrostatic potential (MEP) of the title compounds were investigated by theoretical calculations. Molecular properties such as the ionization potential (I), electron affinity (A), chemical hardness (η), electronic chemical potential (μ), and electrophilicity (ω) were investigated for the structures. Thus, there was an excellent agreement between experimental and theoretical results.

Full text of DOI:10.1155/2020/9483520

Hindawi
Heteroatom Chemistry
Volume 2020, Article ID 9483520, 13 pages
https://doi.org/10.1155/2020/9483520
Research Article
Efficient ZrO(NO3)2.2H2O Catalyzed Synthesis of 1H-Indazolo
[1,2-b] phthalazine-1,6,11(13H)-triones and Electronic Properties
Analyses, Vibrational Frequencies, NMR Chemical Shift Analysis,
MEP: A DFT Study
Forozan Piryaei, Nahid Shajari , and Hooriye Yahyaei
Department of Chemistry, Zanjan Branch, Islamic Azad University, P.O. Box 49195-467, Zanjan, Iran
Correspondence should be addressed to Nahid Shajari; shajari_nahid@yahoo.com
Received 17 August 2019; Revised 26 October 2019; Accepted 11 November 2019; Published 1 March 2020
Academic Editor: Xing-Hai Liu
Copyright © 2020 Forozan Piryaei et al. /is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
/e synthesis of 1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione derivatives, using one-pot three-component condensation
reaction of 3-nitrophthalic anhydride, hydrazine monohydrate, dimedone, and aromatic aldehydes in the presence of
ZrO(NO3)2.2H2O as the novel catalyst and in reflux conditions in EtOH was reported. Quantum theoretical calculations for three
structures of compounds (5a, 5b, and 5c) were performed using the Hartree–Fock (HF) and density functional theory (DFT).
From the optimized structure, geometric parameters were obtained and experimental measurements were compared with the
calculated data. /e structures of the products were confirmed by IR, 1H NMR, 13C NMR, mass spectra, and elemental analyses.
/e IR spectra data and 1H NMR and 13C NMR chemical shift computations of the 1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-
trione derivatives in the ground state were calculated. Frontier molecular orbitals (FMOs), total density of states (DOS),
thermodynamic parameters, and molecular electrostatic potential (MEP) of the title compounds were investigated by theoretical
calculations. Molecular properties such as the ionization potential (I), electron affinity (A), chemical hardness (η), electronic
chemical potential (µ), and electrophilicity (ω) were investigated for the structures. /us, there was an excellent agreement
between experimental and theoretical results.
heterocycles [21–24], we described herein a simple synthesis
of 1H-indazolo[1, 2-b]phthalazinetriones by three-compo-
nent condensation reaction of phthalhydrazide, dimedone,
and aromatic aldehydes in the presence of a catalytic amount
of ZrO(NO3)2.2H2O at reflux conditions in EtOH. In recent
years, computational chemistry has become an important
tool for chemists and a well-accepted partner for experi-
mental chemistry [25]. Computational chemistry is the
application of computer simulation to predict or interpret
chemical reactivity. Computational organic chemistry is an
important area within which occur the determination of the
mechanisms of chemical reactions [26, 27] especially ca-
talysis [28, 29]structural determination of organic com-
pounds [30, 31] prediction of spectroscopic data such as 1H
NMR and 13C NMR chemical shifts [32, 33] properties
calculation of organic molecules [34, 35] and the interaction
1. Introduction
/e nitrogen-containing heterocyclic compounds are ex-
tensive in nature and play a unique role in biological systems
[1–3]. Heterocycles containing the phthalazine ring are
important compounds with broad biological activities, such
as anticonvulsant [4], vasorelaxant [5], cardiotonic [6],
cytotoxic [7], antimicrobial [8], anticonvulsant [9], anti-
fungal [10], anticancer [11], and anti-inflammatory [12].
Several methods have been reported in the literature for the
synthesis of 1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-
trione derivatives which have been reported using
Mg(HSO4)2 [13], [Bmim]Br [14], p-TSA [15], silica sulfuric
acid [16], PPA–SiO2 [17], H2SO4/H2O–EtOH and H2SO4/
[bmim]BF4 [18], Ce(SO4)2.4H2O [19], and starch sulfate
[20], as catalysts. Given the interest in the synthesis of

2
Heteroatom Chemistry
of a substrate with an enzyme [36]. /is study has revealed
some potential leads for possible pharmaceutical applica-
tions, and further research may help in the development of
new antioxidative agents for important metabolic functions.
Also, three new crystal structures of the compounds 5a, 5b,
and 5c are reported. In the present work, we investigated the
energetic and structural properties of three compounds of
1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione deriva-
tives (5a, 5b, and 5c), using the DFT calculations. /e
optimized geometries, quantum molecular descriptors, IR
orbital (ELUMO), HOMO-LUMO energy gap (∆E),
ELUMO, natural charges, and molecular properties [40].
/e optimized molecular structure, HOMO and LUMO
surfaces were visualized using GaussView 03 program [41].
3. Results and Discussion
/e three-component reaction between 3-nitro phthal-
hydrazide (6), dimedone (3), and aromatic aldehydes (4)
proceeded very smoothly and cleanly in the presence of a
catalytic amount of ZrO(NO3)2.2H2O at reflux
conditions in ethanol and afforded the corresponding
1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione deriv-
atives (5a-c) in high yields (Scheme 1 and Table 1), and
no undesirable side reactions were observed. A mecha-
nistic rationalization for this reaction is provided in
Scheme 2. /e structures of the products were deduced
1
spectra data, H NMR and 13C NMR chemical shift com-
putations, molecular electrostatic potential (MEP), ther-
modynamic and electronic properties, and NBO analysis
were calculated through density functional theory (DFT)
and Hartree–Fock (HF) methods.
2. Materials and Methods
1
from their IR, H NMR, 13C NMR, mass spectra and el-
/e starting materials and solvents were obtained from
Merck (Germany) and Fluka (Switzerland) and were used
without further purification. /e melting points were
measured with an Electrothermal 9100 apparatus and were
uncorrected. /e IR spectra were recorded on a Jasco FT-IR
6300 spectrometer. /e 1H NMR and 13C NMR spectra were
measured (CDCl3 solution) with a Bruker DRX-250 Avance
spectrometer at 250.0 and 62.9 MHz, respectively. Mass
spectra were recorded with an Agilent Technologies 5975°C
mass spectrometer. /e elemental analyses were carried out
using a Heraeus CHN-O-rapid analyzer.
emental analyses. For example, the 1H NMR spectrum of 5a
exhibited distinct signals arising from two CH3 groups of
dimedone (0.96 and 1.00 ppm, 2 s), two CH2 groups of
dimedone ring (2.07–2.33 ppm, m) and (3.65 ppm, s), one
OCH3 group of 4-methoxyphenyl ring (3.80 ppm, s), aliphatic
CH (5.25 ppm, s), and seven aromatic CH (7.02 ppm,
d,3JHH = 8.25 Hz),
(7.78 ppm,
d,3JHH = 8.25 Hz),
and
(8.50–8.82, m). /e 13C NMR spectrum of 5a shows 22
distinct resonances arising from two CH3 groups (26.91 and
28.16 ppm), C (32.24 ppm), two CH2 groups (42.49 and
50.74 ppm), OCH3 (55.81 ppm), aliphatic CH (64.46 ppm),
aromatic and olefinic carbons (113.66, 114.83, 127.03, 127.99,
128.71, 129.08, 129.41, 129.96, 130.40, 131.97, 135.29, and
136.87 ppm), and C=O carbons (160.84, 162.12, and
196.47 ppm). /e mass spectrum of 5a displays a molecular
ion peak at m/z 447.
2.1. General Procedure for the Synthesis of 1H-indazolo[1,2-b]
phthalazine-1,6,11(13H)-triones. 3-Nitrophthalic anhydride
(1, 1 mmol) and hydrazine monohydrate (2, 1 mmol)) were
refluxed in ethanol for 15 minutes to form phthalhydrazide
as an intermediate. /en, we added dimedone (3, 1 mmol)
and aromatic aldehydes (4, 1 mmol) to the mixture of this
reaction one by one in the presence of ZrO(NO3)2.2H2O
(2 mol%) and the mixture was refluxed again for 2-3 hours.
/e completion of the reaction was checked by TLC. /e
solvent was removed under reduced pressure, and the vis-
cous residue was purified by a preparative layer chroma-
tography (silica gel; petroleum ether–ethyl acetate (8 : 2)).
/e solvent was removed under a reduced pressure and the
products 5a–c were obtained.
3.1. Characterization Data for the Synthesis of 1H-indazolo
[1,2-b]phthalazine-1,6,11(13H)-trione Derivatives (5a-c)
3.1.1. 3,3-Dimethyl-13-(4-methoxyphenyl)-10-nitro-2,3,4,13-
tetrahydro-1H-indazolo[1,2-b] phthalazine-1,6,11(13H)-tri-
one (5a). Yellow solid; m.p.>250°C; Yield: 75%; Anal. Calcd
for C24H21N3O6 (447.4): C, 64.42; H, 4.73; N, 9.39 %. Found:
C, 64.38; H, 4.75; N, 9.33; IR (KBr) (υmax, cm− 1): 3439, 2959,
1728 (C=O), 1666 (C=O), 1602 (C=O), 1535 (NO2-
1
2.2.ComputationalStudies. In the present study, we carried
out quantum theoretical calculations for the compounds
Asymmetric Str.), 1464, 1358 (NO2-Symmetric Str.); H
NMR (DMSO. d6, 250.0 MHz): δH 0.96 (3H, s, CH3), 1.00
(3H, s, CH3), 2.07–2.33 (2H, m, CH2), 3.65 (2H, s, CH2), 3.80
(3H, s, OCH3), 5.25 (1H, s, CH), 7.02 (2H, d, 3JHH = 8.25 HZ,
arom CH), 7.78 (2H, d, 3JHH = 8.25 HZ, arom CH), 8.50–8.82
(3H, m, arom CH); 13C NMR (DMSO. d6, 62.9 MHz): δC 26.91
and 28.16 (2CH3), 32.24 (C), 42.49 (CH2), 50.74 (CH2), 55.81
(OCH3), 64.46 (CH), 113.66, 114.83, 127.03, 127.99, 128.71,
129.08, 129.41, 129.96, 130.40, 131.97, 135.29, and
136.87 (aromatic and olefinic carbons), 160.84, 162.12, and
196.47 (3C=O); MS (EI): m/z 447 (M+, 0.02), 286 (5), 269
(100), 253 (9), 241 (27), 161 (76), 134 (27), 91 (24), 77 (33), and
63 (13).
∗
∗∗
5a, 5b, and 5c using the HF/6-31+G , HF/6–311+G
,
∗
∗∗
B3LYP/6-31+G , and B3LYP/6–311+G levels [37] by the
Gaussian 03W program package [38] and calculated their
properties. During the beginning stage, we obtained an
optimized structure using Gaussian 03W program (see
Figure 1). /en, we calculated the 1H NMR chemical shifts
∗
∗∗
∗
using the HF/6-31+G , HF/6–311+G , B3LYP/6-31+G ,
∗∗
and B3LYP/6–311+G levels for the title compounds (5a,
5b, and 5c) and 13C NMR [39]. /e electronic properties
included energy of the highest occupied molecular orbital
(EHOMO), energy of the lowest unoccupied molecular

Heteroatom Chemistry
3
Compound A
3
E
LUMO = –0.20 eV
HOMO
2
1
LUMO
ΔE =
0.07 eV
0
E
HOMO = –0.27 eV
–1
Energy (eV)
DOS spectrum
Occupied orbitals
Virtual orbitals
Compound B
3
E
LUMO = –0.19 eV
LUMO
HOMO
2
1
ΔE =
0.08 eV
0
E
HOMO = –0.27 eV
–1
Energy (eV)
DOS spectrum
Occupied orbitals
Virtual orbitals
Compound C
3
ELUMO = –0.23 eV
2
1
HOMO
LUMO
ΔE =
0.06 eV
0
EHOMO = –0.29 eV
–1
Energy (eV)
(b)
DOS spectrum
Occupied orbitals
Virtual orbitals
(a)
Figure 1: (a) Calculated frontier molecular orbitals of compounds 5a, 5b, and 5c (ΔE: energy gap between LUMO and HOMO).
(b) Calculated DOS plots of the title compounds (using B3LYP/6-311+G(d)).
3.1.2. 3,3-Dimethyl-10-nitro-13-phenyl-2,3,4,13-tetrahydro-
66.25; H, 4.54; N, 10.00; IR (KBr) (υmax, cm− 1): 2931, 2358,
1724 (C�O), 1617 (C�O), 1588 (C�O), 1539 (NO2-Asym-
1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione
(5b).
1
Yellow solid; m.p.>250°C; Yield: 80%; Anal. Calcd for
metric Str.), 1460, 1410 (NO2 - Symmetric Str.); H NMR
C23H19N3O5 (417.4): C, 66.18; H, 4.59; N, 10.07 %. Found: C,
(DMSO. d6, 250.0 MHz): δH 0.96 (3H, s, CH3), 1.24 (3H, s,

4
Heteroatom Chemistry
NO2
O
O
NO2
Ar
O
O
O
O
N
N
ZrO(NO3)2.2H2O
Ethanol, reflux
O
+
NH2NH2.H2O
+
ArCHO
+
O
(1)
(2)
(3)
(4)
(5)
Scheme 1: /ree-component reaction of 3-nitrophthalic anhydride, hydrazine monohydrate, dimedone, and aromatic aldehydes (see
Table 1).
Table 1: Synthesis of 1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione derivatives (5a-c).
5
Ar
% Yield
a
b
c
4-Methoxyphenyl
Phenyl group
4-Chlorophenyl group
75
80
78
NO2
O
O
+
NH2NH2.H2O
(2)
(1)
O
O
NO2
NH
NH
O
O
O2N
O
(6)
O
NH
–H2O
+
N
O
N
O
Ar
O2N
Ar
N
O
O
Ar
O
O
(5)
(10)
(11)
O
d
H
n
a
r O
– Z
O
+2OZr
Ar
H
O
O
(9)
ZrO+2
Ar
O
O
O
O
ZrO+2
O
H
+
O
H
Ar
H
(8)
(3)
(4)
(7)
Scheme 2: A proposed mechanism for the formulation of 1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione derivatives (5a-c).

Heteroatom Chemistry
5
CH3), 2.07–2.23 (2H, m, CH2), 3.87–3.92 (2H, m, CH2), 5.26
(1H, s, CH), 7.36–8.69 (9H, m, arom CH); 13C NMR (DMSO.
d6, 62.9 MHz): δC 28.15 and 28.50 (2CH3), 32.47 (C), 42.49
(CH2), 50.74 (CH2), 64.44 (CH), 126.81, 128.29, 128.44,
128.56, 128.79, 129.14, 129.32, 130.78, 131.76, 131.95, 134.25,
and 135.31 (aromatic and olefinic carbons), 161.82, 165.50,
and 198.19 (3C�O).
results belong to the solid phase while theoretical calcula-
tions belong to the isolated gaseous phase.
3.2.2. NMR Parameters. /e calculation of 1H NMR and 13
C
NMR chemical shifts of compounds 5a, 5b, and 5c is done at
B3LYP/3-21G, HF/3-21G, B3LYP/6-311+G(d), and HF/6-
1
311+G(d) levels. /e experimental and calculated H NMR
and 13C NMR chemical shifts of 1H-indazolo[1,2-b]
phthalazine-1,6,11(13H)-trione derivatives (5a, 5b and 5c)
are presented in Tables 5–10. Based on our calculations and
experimental spectra, we made a reliable one-to-one cor-
respondence between our fundamentals, and all of the
chemical shifts were calculated by the HF and B3LYP
methods. For the title compound (5a), the aromatic CH
protons appeared at δH 7.02–8.82 ppm, and the calculated
3.1.3. 13-(4-Chlorophenyl)-3,3-dimethyl-10-nitro-2,3,4,13-
tetrahydro-1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-tri-
one (5c). Yellow Solid; m.p. >250°C; Yield: 78%; Anal. Calcd
for C23H18ClN3O5 (451.9): C, 61.14; H, 4.02; N, 9.30 %.
Found: C, 61.10; H, 4.04; N, 9.24; IR (KBr) (υmax, cm− 1):
2928, 2358, 1728 (C�O), 1611 (C�O), 1591 (C�O), 1474
(NO2- Asymmetric Str.), 1393 (NO2-Symmetric Str.), 1085
∗∗
∗∗
1
amounts at HF/6-311+G and B3LYP/6-311+G basis set
levels were at 7.30–8.19 and 7.00–8.89 ppm, respectively.
Protons of two methyl groups appeared at δH 0.96 and
(C–Cl); H NMR (DMSO. d6, 250.0 MHz): δH 0.94 (3H, s,
CH3), 1.22 (3H, s, CH3), 2.05–2.20 (2H, m, CH2), 3.87 (2H, s,
CH2), 5.23 (1H, s, CH), 7.15–8.66 (8H, m, arom CH); 13C
NMR (DMSO. d6, 62.9 MHz): δC 26.82 and 28.12 (2CH3),
32.45(C), 42.43 (CH2), 50.68 (CH2), 64.45 (CH), 114.38,
123.32, 128.22, 128.67, 128.90, 129.07, 129.26, 129.46,
129.89, 130.34, 133.01, and 134.70 (aromatic and olefinic
carbons), 161.00, 163.41, and 196.43 (3C�O).
∗∗
1.00 ppm, the calculated amounts at HF/6-311+G and
∗∗
B3LYP/6-311+G basis set levels were at 0.67 and 1.28 ppm
and 0.86 and 1.19 ppm, respectively. Also, chemical shifts of
three carbonyl groups appeared at δc 160.84, 162.12, and
∗∗
196.47 ppm, the calculated amounts at HF/6-311+G and
∗∗
B3LYP/6-311+G basis set levels were at 149.88, 153.99,
and 190.97 ppm and 159.51, 161.27, and 197.32 ppm, re-
spectively. /e same was true for other compounds.
/ere was an excellent agreement between experimental
and theoretical results for all methods employed. In order to
compare this agreement, the correlation graphic based on
the theoretical and experimental data was investigated. /e
correlation value (R2) for compounds at HF/3-21G, B3LYP/
3.2. Computational Section
3.2.1. IR Spectroscopy. Harmonic vibrational frequencies of
the title compounds were calculated using the B3LYP/3-21G,
HF/3-21G, B3LYP/6-311+G(d), and HF/6-311+G(d) levels.
/e vibrational frequencies assignments were made using
the GaussView program. Some of the characteristic fre-
quencies are provided in Tables 2–4. /e harmonic fre-
quencies calculated by DFT are usually higher than the
corresponding experimental values due to the approximate
treatment of the electron correlation, anharmonicity effects,
and basis set deficiencies [39].
∗∗
∗∗
3-21G, HF/6-311+G , and B3LYP/6-311+G is presented
in Table 11. /ere was an excellent agreement between
experimental and theoretical results [39]. A small difference
between the experimental and calculated vibrational modes
was observed. /is difference might have been due to the
intermolecular hydrogen bonding formation. Furthermore,
the experimental results belong to the solid phase while and
theoretical calculations belong to the isolated gaseous phase.
For the title compound (5a), the strong band at
3376 cm− 1 in the FT-IR spectrum is assigned as vC=O mode.
/e calculated values for this mode are 3375, 3204, 3227, and
∗
∗∗
3360 cm− 1 for HF/6-31+G , HF/6–311+G , B3LYP/6-
∗
∗∗
31+G , and B3LYP/6–311+G levels, respectively. For the
title compound (5a), the strong band at 3439, 2959, and
1728 cm− 1 in the FT-IR spectrum is assigned as vC=O mode.
/e calculated values for this mode are the same as those
3.2.3. Electronic Properties. Quantum chemical methods are
important for obtaining information about molecular
structure and electrochemical behavior. A frontier molecular
orbital (FMO) analysis was performed for the compounds
using the B3LYP/6-311+G(d) level [38]. FMO results such as
EHOMO, ELUMO, and the HOMO-LUMO energy gap
(∆E) of the title compounds are summarized in Table 7. /e
energy of the LUMO, HOMO, and their energy gaps re-
flected the chemical reactivity of the molecule [43]. In ad-
dition, the HOMO could act as an electron donor and the
LUMO as an electron acceptor. A higher HOMO energy
(EHOMO) for the molecule indicated a higher electron-
donating ability to an appropriate acceptor molecule with a
low-energy empty molecular orbital [44]. As shown in
Figure 1 the HOMO energy of the compound 5c had the
highest value (− 0.29 eV). A large energy gap implied high
stability for the molecule. /e calculated values of the
∗∗
calculated for HF/3-21G, HF/6-311+G , B3LYP/3-21G, and
B3LYP/6-311+G levels, respectively. /e DFT computa-
∗∗
tion predicts this vibrational mode in ArC=C at 1464 cm− 1
for A, 1489 cm− 1 for the compound 5b, and 1493 cm− 1 for
the compound 5c. /is observed frequency coincides well
with the expected value [42]. /ere was an excellent
agreement between experimental and theoretical results for
all used methods. In order to compare this agreement, the
correlation graphic based on the theoretical and experi-
mental data was investigated. A small difference between the
experimental and calculated vibrational modes was ob-
served. /is difference might have been due to intermo-
lecular hydrogen bonding formation. Also, the experimental

6
Heteroatom Chemistry
Table 2: /e selected experimental and theoretical frequencies of the title compounds using the B3LYP and HF methods for compound (5a).
Experimental wavenumbers by FT-IR (cm− 1
)
Calculated vibrational wavenumbers by HF and DFT methods (cm− 1
)
B3LYP
HF
∗∗
∗∗
3-21G
6-311+G
3-21G
6-311+G
3439
2959
1728
1666
1602
1535
1464
1358
3441
2967
1721
1691
1602
1599
1466
1351
3440
2955
1729
1673
1608
1530
1466
1359
3438
2964
1720
1689
1615
1542
1463
1368
3450
2960
1733
1682
1600
1535
1469
1366
C�O
C�O
C�O
Assignment
C�C
Ar C�C
CH3
Table 3: /e selected experimental and theoretical frequencies of the title compounds using the B3LYP and HF methods for compound
(5b).
Experimental wavenumbers by FT-IR (cm− 1
)
Calculated vibrational wavenumbers by HF and DFT methods (cm− 1
)
B3LYP
HF
∗∗
∗∗
3-21G
6-311+G
3-21G
6-311+G
3413
3413
2972
1660
1619
1573
1489
1397
1080
3405
2915
1663
1628
1588
1490
1362
1090
3461
2952
1668
1630
1589
1498
1373
1099
3423
2962
1671
1629
1573
1499
1307
1088
C�O
C�O
2955
1661
1626
1583
1489
1362
1090
Assignment
C�H
Ar C�C
CH3
C–Cl, bending
Table 4: /e selected experimental and theoretical frequencies of the title compounds using the B3LYP and HF methods for compound (5c).
Experimental wavenumbers by FT-IR (cm− 1
)
Calculated vibrational wavenumbers by HF and DFT methods (cm− 1
)
B3LYP
HF
∗∗
∗∗
3-21G
6-311+G
3-21G
6-311+G
3436
2951
1661
1625
1576
1492
1361
3430
2971
1669
1638
1583
1483
1361
3430
2962
1661
1640
1579
1492
1361
3449
2973
1750
1615
1580
1489
1373
3435
2943
1665
1635
1579
1497
1360
C�O
Assignment
C�O
C�C
Ar C�C
CH3
1
Table 5: Experimentally measured and calculated H chemical shifts δ (ppm vs TMS) of the compound (5a).
Calculated
B3LYP/6-311+G
1H NMR
EXP
∗∗
∗∗
B3LYP/3-21G
HF/3-21G
HF/6-311+G
3H, s, CH3
0.96
1.00
0.33
1.41
0.86
1.19
0.66
1.15
0.67
1.28
3H, s, CH3
2H, m, CH2
2.07–2.33
3.65
2.38–2.52
3.32
2.03–2.33
3.60
1.95–2.60
3.13
1.95–2.60
3.13
2H, s, CH2
3H, s, OCH3
1H, s, CH
3.80
3.78
3.88
3.66
3.66
5.25
5.25
5.50
5.81
5.81
2H, d, arom C–H
2H, d, arom C–H
4H, m, arom C–H
7.02
7.02
7.00
7.30
7.30
7.78
7.11
7.70
7.44
7.44
8.50–8.82
8.22–8.75
8.51–8.89
8.08–8.17
8.08–8.19
HOMO-LUMO energy gap (∆E) for the structures 5a, 5b,
and 5c were 0.07, 0.08, and 0.06 eV, respectively. DOS plots
[45] also demonstrated the calculated energy gaps (∆E) for
the compounds 5a, 5b, and 5c (see Figure 2). It is obvious
that the energy gap of the compound 5b was the highest
(0.08 eV); therefore, it was less reactive than the other

Heteroatom Chemistry
Table 6: Experimentally measured and calculated 13C chemical shifts δ (ppm vs TMS) of the compound (5a).
7
Calculated
B3LYP/6-311+G
13C NMR
EXP
∗∗
∗∗
B3LYP/3-21G
HF/3-21G
HF/6-311+G
2CH3
C
26.91–28.16
32.24
26.26–27.78
31.10
42.83
49.01
63.98
50.11
93.78
94.99
95.08
95.39
96.14
96.87
97.60
97.65
119.1
122.79
127.76
129.30
—
26.90–27.99
31.99
18.82–30.50
32.62
26.80–27.01
30.37
CH2
CH2
CH
42.49
42.73
45.54
44.99
50.74
49.41
46.01
46.89
64.46
62.99
55.88
58.79
60.74
OCH3
55.81
48.72
50.11
113.66
114.83
127.99
128.71
128.71
129.08
129.41
129.96
130.40
131.97
135.29
136.87
160.84
162.12
196.47
113.52
113.99
126.31
130.07
131.05
130.66
133.98
136.75
138.41
101.98
108.88
110.44
111.47
112.90
113.02
114.13
114.48
114.56
127.99
137.19
138.90
—
107.09
111.90
123.53
123.43
122.90
125.51
124.39
124.19
124.97
126.65
137.19
144.90
149.88
153.99
190.97
C-H aromatic and olefinic carbons
C=O(1)
C=O(2)
C=O(3)
159.51
161.27
197.32
—
—
—
—
1
Table 7: Experimentally measured and calculated H chemical shifts δ (ppm vs TMS) of the compound (5b).
Calculated
B3LYP/6-311+G
1H NMR
EXP
∗∗
∗∗
B3LYP/3-21G
HF/3-21G
HF/6-311+G
3H, s, CH3
3H, s, CH3
0.94
1.22
0.43
1.42
0.98
1.27
0.48
1.30
0.97
1.30
2H, m, CH2
2H, s, CH2
2.05–2.20
3.87
2.11–2.32
3.94
2.08–2.28
3.90
2.17–2.96
4.00
2.09–2.48
3.98
1H, s, C–H
5.23
5.63
5.32
5.85
5.42
8H, m, arom C–H
7.15–8.66
7.10–7.97
7.17–8.62
7.19–8.91
7.19–8.76
Table 8: Experimentally measured and calculated 13C chemical shifts δ (ppm vs TMS) of the compound (5b).
Calculated
B3LYP/6-311+G
13C NMR
EXP
∗∗
∗∗
B3LYP/3-21G
HF/3-21G
HF/6-311+G
2CH3
C
CH2
CH2
CH
26.82–28.12
32.45
26.43–29.11
37.41
43.33
58.13
70.41
86.90
93.88
94.84
97.22
97.71
97.97
100.82
101.89
119.29
127.48
129.17
148.29
—
26.83–29.11
32.51
25.31–31.74
36.42
41.23
59.11
72.31
89.99
97.67
97.91
83.23
84.89
85.99
112.92
113.55
114.41
129.99
130.89
137.98
—
28.88–30.11
36.77
42.43
42.51
42.21
50.68
51.67
57.32
64.45
63.78
71.20
114.38
123.32
128.22
128.67
128.90
129.07
129.26
129.46
129.89
130.34
133.01
134.70
161.00
163.41
115.77
123.46
129.22
129.63
129.77
130.11
130.28
130.49
130.80
131.45
134.89
135.03
160.27
162.11
85.90
91.63
96.41
126.99
128.71
128.86
128.32
129.27
129.64
129.83
130.22
134.60
159.21
160.41
Aromatic and olefinic carbons
C=O(1)
C=O(2)
—
—

8
Heteroatom Chemistry
1
Table 9: Experimentally measured and calculated H chemical shifts δ (ppm vs TMS) of the compound (5c).
Calculated
B3LYP/6-311+G
1H NMR
EXP
∗∗
∗∗
B3LYP/3-21G
HF/3-21G
HF/6-311+G
3H, s, CH3
3H, s, CH3
0.96
1.24
0.53
1.40
0.97
1.29
0.69
1.84
0.78
1.48
2H, m, CH2
2H, m, CH2
1H, s, C-H
2.07–2.23
3.87–3.92
5.26
1.83–2.32
2.86
2.11–2.29
3.80–3.94
5.23
1.95–2.10
3.10–3.51
5.88
1.96–2.11
3.18–3.68
5.40
5.59
9H, m, arom C-H
7.36–8.69
7.06–7.19
7.33–8.68
7.18–8.16
7.11–8.39
Table 10: Experimentally measured and calculated 13C chemical shifts δ (ppm vs TMS) of the compound (5c).
Calculated
B3LYP/6-311+G
13C NMR
EXP
∗∗
∗∗
B3LYP/3-21G
HF/3-21G
HF/6-311+G
CH3
CH3
C
CH2
CH2
CH
28.15
28.50
26.66
28.19
30.11
43.86
50.11
73.11
87.066
92.77
92.93
93.60
93.23
96.53
97.06
97.73
102.53
119.2
127.6
129.46
—
28.19
28.93
18.20
18.70
28.21
28.87
32.47
33.11
30.65
32.76
42.49
47.22
45.64
48.32
50.74
50.66
48.11
50.98
64.44
64.32
48.91
67.11
126.81
128.29
128.44
128.67
128.86
129.14
129.32
130.78
131.76
131.95
134.25
135.31
161.82
165.50
198.19
127.93
129.48
129.32
129.51
129.69
130.11
130.30
130.79
133.35
133.78
133.86
139.21
163.23
169.93
197.11
107.92
108.21
108.43
108.74
108.56
109.85
110.05
110.48
112.03
113.08
114.19
118.79
151.46
153.24
169.84
128.01
128.32
128.66
128.51
128.90
133.66
133.68
133.99
136.98
136.31
136.32
137.38
160.20
161.39
193.22
Aromatic and olefinic carbons
C=O(1)
C=O(2)
C=O(3)
—
—
1
Table 11: Correlation of calculated and experimental H NMR,13C NMR, and IR of the compounds.
∗∗
∗∗
Compounds
B3LYP/3-21G
B3LYP/6-311+G
HF/3-21G
HF/6-311+G
5a
5b
5c
0.9975
0.9986
0.9996
0.9999
0.9999
0.9995
0.9991
0.9985
0.9990
0.9974
0.9997
0.9998
HNMR
5a
5b
5c
5a
5b
5c
0.9977
0.9983
0.9986
0.9953
0.9986
0.9970
0.9995
0.9999
0.9998
0.9995
0.9999
0.9997
0.9992
0.9990
0.9998
0.9995
0.9988
0.9983
0.9975
0.9998
0.9999
0.9978
0.9990
0.9991
CNMR
IR
structures, whereas the energy gap of the compound 5c was
the lowest (0.06 eV), which indicates that it was the most
reactive. As presented in Figure 2, charge transfer could take
place within the three molecules.
/e electronic properties such as ionization potential,
electron affinity, global hardness, electronic chemical po-
tential, and electrophilicity are calculated in Table 12. /e first
ionization potential (I) and electron affinity (A) could be
expressed through HOMO and LUMO orbital energies by
connecting it with Hartree–Fock SCF theory and invoking
Koopmans' theorem [46] as I = − EHOMO and A = − ELUMO.
/e chemical hardness (η = I− A/2) is an important property
that measures the molecular stability and reactivity [47]. A
hard molecule has a large energy gap (∆E) and a soft molecule
has a small energy gap (∆E) [48]. /e chemical hardness (η)
values of the compounds 5a, 5b, and 5c were 0.170, 0.176, and
0.175 eV, respectively. Compound 5b had the highest
chemical hardness (η = 0.176 eV); therefore, it was a hard

Heteroatom Chemistry
9
(a)
(b)
Figure 2: Continued.

10
Heteroatom Chemistry
(c)
Figure 2: Molecular electrostatic potential (MEP) maps of the title compounds calculated using the B3LYP/6-311+G(d) level.
molecule with less reactivity and a high energy gap
(∆E = 0.08 eV). /e electronic chemical potential (µ = − (I + A)/
2) is a form of the potential energy that can be absorbed or
released during a chemical reaction and that may also change
during a phase transition [49]. /e electronic chemical po-
tential of 5c had the most negative value (− 0.26 eV). /e
electrophilicity (ω) measures the stabilization in energy when
the system acquires an additional electronic charge from the
environment. /e electrophilicity index (ω = µ2/2η) contains
information about both electron transfer (chemical potential)
and stability (hardness) and is a better descriptor of global
chemical reactivity [50]. /e higher value of electrophilicity
index shows the high capacity of the molecule to accept
electrons. /e electrophilicity index for the compounds 5a, 5b,
and 5c was 0.0040, 0.0046, and 0.0059 eV, respectively. /e
compound 5c had the highest electrophilicity index; therefore,
it had a high capacity for accepting electrons. /e dipole
moment (µD) is a good measure of the asymmetric nature of a
molecule. /e size of the dipole moment depends on the
composition and dimensionality of the 3D structures. As
shown in Table 12, all structures had a high value of dipole
moment and point group of C1, which reflected no symmetry
in the structures. /e dipole moment for the compound 5b
(B3LYP/6-311+G(d) = 6.172 Debye) was higher than that for
the compounds 5a and 5c (4.988 and 4.396 Debye, respecti-
vely)./e high value for 5c was due to its asymmetric character.
considering the molecule to be at room temperature of 25°C
and 1 atmospheric pressure. /e thermodynamic parame-
ters such as zero-point vibrational energy, rotational con-
stant, heat capacity (C), and the entropy (S) of the title
compound by B3LYP/6-311+G(d) level are listed in Table 13.
According to Table 13, the calculated values for compound
5a and 5b are larger than compound 5c; therefore, com-
pounds 5a and 5b have maximum stability compared to
compound 5c due to formation of intramolecular hydrogen
bonding.
3.2.5. Molecular Electrostatic Potential (MEP). /e molec-
ular electrostatic potential (MEP) was calculated by the
B3LYP/6-311+G (d) level. /e MEP is related to the elec-
tronic density and is a very useful descriptor in under-
standing sites for electrophilic attack and nucleophilic
reactions as well as hydrogen bonding interactions [45]. /e
negative regions (red color) of the MEP are related to
electrophilic reactivity, and the positive (blue color) region is
related to nucleophilic reactivity, as shown in Figure 2.
Molecular electrostatic potential (MEP) surface aims at
locating the positive and negative charged electrostatic
potential in the molecule. In each MEP surface, there is a
color scale which indicates the negative and positive value.
/e red color is a sign for the negative extreme, and the blue
color represents the positive extreme. /e red color with a
negative sign indicates the minimum electrostatic potential
(which means it is bound loosely or has excess electrons),
and it acts as electrophilic attack. /e blue color also in-
dicates the maximum of electrostatic potential, and it acts in
the opposite manner.
3.2.4. >ermodynamic Analysis. /e total energy of a
molecule consists of the sum of translational, rotational,
vibrational, and electronic energies. /e statistical ther-
mochemical analysis of title compounds is carried out

Heteroatom Chemistry
11
Table 12: Absolute energy (a.u), dipole moment (μ, Debye), frontier orbital energies (HOMO and LUMO, eV), hardness (η, eV), chemical
potential (μ, eV), and electrophilicity (ω, eV) of 5a, 5b, and 5c molecules.
EHOMO
ELUMO
I
A
µ
η
ω
µD
Point group
5a
5b
5c
− 0.27
− 0.27
− 0.29
− 0.20
− 0.19
− 0.23
0.27
0.27
0.29
0.20
0.19
0.23
− 0.235
− 0.230
− 0.260
0.170
0.176
0.175
0.0040
0.0046
0.0059
4.988
6.172
4.396
C1
C1
C1
Table 13: /ermodynamic parameters of the 5a, 5b, and 5c molecules using the B3LYP/6-311+G(d) level.
5a
0.439579
0.468575
0.469519
0.377501
− 1522.507825
− 1522.478830
− 1522.477886
− 1522.569904
294.035
5b
0.394413
0.422073
0.423017
0.333551
− 1864.121732
− 1864.094072
− 1864.093128
− 1864.182594
264.855
5c
0.405306
0.431620
0.432564
0.346912
− 1409.523823
− 1409.497509
− 1409.496565
− 1409.582218
270.846
Zero-point correctiona
/ermal correction to energyb
/ermal correction to enthalpyc
/ermal correction to Gibbs free energyd
Sum of electronic and zero-point energiese
Sum of electronic and thermal energiesf
Sum of electronic and thermal enthalpiesg
Sum of electronic and thermal free energiesh
E (/ermal)i
CVj
109.323
193.668
104.085
188.297
100.028
180.271
Sk
i
a-hHartree/particle; KCal/Mol; j,kCal/Mol-Kelvin.
Starting from the above note, if we plot all MEP surfaces
with all isosurface values, we see only the top surface. It is
observed from the MEP map in Figure 2 that the nitrogen-
bonded oxygen atoms in the NO2 group and the oxygen
atoms in the carbonyl groups (C�O) of the rings are negative
regions in all compounds because in the resonance form of
the nitro group, the oxygen atoms have a negative charge
and the nitrogen atom has a positive charge, and in the
resonance form of the carbonyl groups, the oxygen atoms
have a negative charge and the carbon atom has a positive
charge. /us, oxygen atoms are sites for electrophilic ac-
tivity. /e nitrogen atoms in the ring, which are attached to
carbonyl lethal electron groups, are also positively charged;
therefore, nitrogen atoms are sites for nucleophilic attrac-
tion. As such, these sites provide information about the
regions where the compounds can have strong intermo-
lecular interactions.
electrostatic potential (MEP) of the title compounds were
investigated through theoretical calculations.
Data Availability
No data were used to support this study.
Conflicts of Interest
/e authors declare that they have no conflicts of interest.
Acknowledgments
/e authors are thankful to the Zanjan Branch, Islamic Azad
University, for partial support of this work.
Supplementary Materials
Figure S1: 1H NMR (62.9 MHz, DMSO) spectrum of 3,3-di-
4. Conclusion
methyl-13-(4-methoxyphenyl)-10-nitro-2,3,4,13-tetrahy-
In the present study, the three-component reaction between
3-nitrophthalic anhydride, hydrazine monohydrate, dime-
done, and aromatic aldehydes in the presence of a novel
catalytic amount of ZrO(NO3)2.2H2O to produce 1H-
indazolo[1,2-b]phthalazine-1,6,11(13H)-trione derivatives
was reported. /e reported method offers a mild and effi-
cient procedure for the preparation of these compounds.
/ese compounds of the products were confirmed by IR, 1H
NMR, 13C NMR, mass spectra, and elemental analyses. /e
dro-1H-indazolo[1,2-b]
phthalazine-1,6,11(13H)-trione
(5a). Figure S2: 13C NMR (62.9 MHz, DMSO) spectrum of
3,3-dimethyl-13-(4-methoxyphenyl)-10-nitro-2,3,4,13-tet-
rahydro-1H-indazolo[1,2-b] phthalazine-1,6,11(13H)-trione
(5a). Figure S3: mass spectrum of 3,3-dimethyl-13-
(4-methoxyphenyl)-10-nitro-2,3,4,13-tetrahydro-1H-inda-
zolo[1,2-b] phthalazine-1,6,11(13H)-trione (5a). Figure S4:
1H NMR (62.9 MHz, DMSO) spectrum of 3,3-dimethyl-
10-nitro-13-phenyl-2,3,4,13-tetrahydro-1H-indazolo[1,2-b]
phthalazine 1,6,11(13H)-trione (5b). Figure S5: 13C NMR
(62.9 MHz, DMSO) spectrum of 3,3-dimethyl-10-nitro-13-
phenyl-2,3,4,13-tetrahydro-1H-indazolo[1,2-b] phthalazine-
1,6,11(13H)-trione (5b). Figure S6: 1H NMR (62.9 MHz,
DMSO) spectrum of 13-(4-chlorophenyl)-3,3-dimethyl-10-
nitro-2,3,4,13-tetrahydro-1H-indazolo[1,2-b]-phthalazine-
IR spectra data and H NMR and 13C NMR chemical shift
1
computations of the 1H-indazolo[1,2-b] phthalazine-
1,6,11(13H)-trione derivatives in the ground state were
calculated. /ere was an excellent agreement between ex-
perimental and theoretical results. Frontier molecular or-
bitals (FMOs), total density of states (DOS), and molecular

12
Heteroatom Chemistry
1,6,11(13H)-trione (5c). Figure S7: 13C NMR (62.9 MHz,
DMSO) spectrum of 13-(4-chlorophenyl)-3,3-dimethyl-10-
nitro-2,3,4,13-tetrahydro-1H-indazolo[1,2-b]-phthalazine-
1,6,11(13H)-trione (5c) (Supplementary Materials)
indazolo[2,1-b]phthalazine-triones in neutral ionic liquid 1-
butyl-3-methylimidazolium bromide,” Ultrasonics Sono-
chemistry, vol. 19, no. 2, pp. 307–313, 2012.
[15] M. Sayyafi, M. Seyyedhamzeh, H. R. Khavasi, and A. Bazgir,
“One-pot, three-component route to 2H-indazolo[2,1-b]
phthalazine-triones,” Tetrahedron, vol. 64, no. 10,
pp. 2375–2378, 2008.
References
[16] H. R. Shaterian, M. Ghashang, and M. Feyzi, “Silica sulfuric
acid as an efficient catalyst for the preparation of 2H-indazolo
[2,1-b]phthalazine-triones,” Applied Catalysis A: General,
vol. 345, no. 2, pp. 128–133, 2008.
[1] M. Azab, M. Youssef, and E. El-Bordany, “Synthesis and
antibacterial evaluation of novel heterocyclic compounds
containing a sulfonamido moiety,” Molecules, vol. 18, no. 1,
pp. 832–844, 2013.
[17] H. R. Shaterian, A. Hosseinian, and M. Ghashang, “Reusable
silica supported poly phosphoric acid catalyzed three-com-
ponent synthesis of 2H-indazolo[2,1-b]phthalazine- trione
derivatives,” Arkivoc, vol. 2009, no. 2, pp. 59–67, 2009.
[18] J. M. Khurana and D. Magoo, “Efficient one-pot syntheses of
2H-indazolo[2,1-b]phthalazine-triones by catalytic H2SO4 in
water–ethanol or ionic liquid,” Tetrahedron Letters, vol. 50,
no. 52, pp. 7300–7303, 2009.
[19] E. Mosaddegh and A. Hassankhani, “A rapid, one-pot, four-
component route to 2H-indazolo[2,1-b]phthalazine-triones,”
Tetrahedron Letters, vol. 52, no. 4, pp. 488–490, 2011.
[20] H. R. Shaterian and F. Rigi, “Starch sulfate as an efficient and
biodegradable polymer catalyst for one-pot, four-component
reaction of 2H-indazolo[2,1-b]phthalazine-triones,” Starch-
Sta¨rke, vol. 63, no. 6, pp. 340–346, 2011.
[2] P. Martins, J. Jesus, S. Santos et al., “Heterocyclic anticancer
compounds: recent advances and the paradigm shift towards
the use of nanomedicine’s tool box,” Molecules, vol. 20, no. 9,
pp. 16852–16891, 2015.
[3] F. W. Lichtenthaler, “Unsaturated O- and N-heterocycles
from carbohydrate feedstocks,” Accounts of Chemical Re-
search, vol. 35, no. 9, pp. 728–737, 2002.
[4] S. Grasso, G. De Sarro, A. De Sarro et al., “Synthesis and
anticonvulsant activity of novel and potent 6,7-methyl-
enedioxyphthalazin-1(2H)-ones,” Journal of Medicinal
Chemistry, vol. 43, no. 15, pp. 2851–2859, 2000.
[5] N. Watanabe, Y. Kabasawa, Y. Takase et al., “4-Benzylamino-
1-chloro-6-substituted phthalazines: synthesis and inhibitory
activity toward phosphodiesterase 5,” Journal of Medicinal
Chemistry, vol. 41, no. 18, pp. 3367–3372, 1998.
[6] Y. Nomoto, H. Obase, H. Takai, M. Teranishi, J. Nakamura,
and K. Kubo, “Studies on cardiotonic agents. II. Synthesis of
novel phthalazine and 1,2,3-benzotriazine derivatives,”
[21] A. Ramazani, Y. Ahmadi, M. Rouhani, N. Shajari, and
A. Souldozi, “/e reaction of (N-isocyanimino) triphenyl-
phosphorane with an electron-poor α-haloketone in the
presence of aromatic carboxylic acids: a novel three-com-
ponent reaction for the synthesis of disubstituted 1,3,4-oxa-
diazole derivatives,” Heteroatom Chemistry, vol. 21, no. 6,
pp. 368–372, 2010.
[22] A. Ramazani, N. Shajari, A. Mahyari, and Y. Ahmadi, “A novel
four-component reaction for the synthesis of disubstituted
1,3,4-oxadiazole derivatives,” Molecular Diversity, vol. 15,
no. 2, pp. 521–527, 2011.
[23] N. Shajari, R. Kazemizadeh, and A. Ramazani, “Efficient one-
pot, four-component synthesis of N,N-dibenzyl-N-{1-[5-(3-
aryl)-1,3,4-oxadiazol-2-yl]cyclobutyl}amine derivatives from
the reaction of (isocyanoimino)triphenylphosphorane,
dibenzylamine, an aromatic carboxylic acid and cyclo-
butanone,” Journal of the Serbian Chemical Society, vol. 77,
no. 9, pp. 1175–1180, 2012.
[24] N. Shajari, R. Ghiasi, and A. Ramazani, “One-pot synthesis of
2-acylaminobenzimidazoles from the reaction between tri-
chloroacetyl isocyanate and 1,2-phenylenediamine derivatives
and theoretical study of structure and properties of synthe-
sized 2-acylaminobenzimidazoles,” Journal of the Chilean
Chemical Society, vol. 63, no. 2, pp. 3968–3973, 2018.
[25] R. B. Nazarski, “Physical imageversusstructure relation. Part
14-an attempt to rationalize some acidic region 13C NMR-pH
titration shifts for tetraaza macrocycles throughout the
conformational GIAO DFTcomputational results: a pendant-
armcyclamcase,” Journal of Physical Organic Chemistry,
vol. 22, no. 9, pp. 834–844, 2009.
Chemical
& Pharmaceutical Bulletin, vol. 38, no. 8,
pp. 2179–2183, 1990.
[7] J. S. Kim, H.-K. Rhee, H. J. Park, S. K. Lee, C.-O. Lee, and
H.-Y. Park Choo, “Synthesis of 1-2-substituted-[1,2,3]triazolo
[4,5-g]phthalazine-4,9-diones and evaluation of their cyto-
toxicity and topoisomerase II inhibition,” Bioorganic & Me-
dicinal Chemistry, vol. 16, no. 8, pp. 4545–4550, 2008.
[8] S. El-Shakka, A. Soliman, and A. Imam, “Synthesis, antimi-
crobial activity and electron impact of mass spectra of
phthalazine-1,4-dione derivatives,” Afinidad, vol. 66, no. 544,
pp. 167–172, 2009.
[9] L. Zhang, L.-P. Guan, X.-Y. Sun, C.-X. Wei, K.-Y. Chai, and
Z.-S. Quan, “Synthesis and anticonvulsant activity of 6-
Alkoxy-[1,2,4]Triazolo[3,4-a]Phthalazines,” Chemical Biology
& Drug Design, vol. 73, no. 3, pp. 313–319, 2009.
[10] C.-K. Ryu, R.-E. Park, M.-Y. Ma, and J.-H. Nho, “Synthesis
and antifungal activity of 6-arylamino-phthalazine-5,8-diones
and 6,7-bis(arylthio)-phthalazine-5,8-diones,” Bioorganic &
Medicinal Chemistry Letters, vol. 17, no. 9, pp. 2577–2580,
2007.
[11] J. Li, Y.-F. Zhao, X.-Y. Yuan, J.-X. Xu, and P. Gong, “Synthesis
and anticancer activities of novel 1,4-disubstituted phthala-
zines,” Molecules, vol. 11, no. 7, pp. 574–582, 2006.
[12] J. Sinkkonen, V. Ovcharenko, K. N. Zelenin et al., “1H and 13
C
NMR study of 1-Hydrazino-2,3-dihydro-1H-pyrazolo[1,2-a]
pyridazine-5,8-diones and -1H-pyrazolo[1,2-b]phthalazine-
5,10-diones and their ring-chain tautomerism,” European
Journal of Organic Chemistry, vol. 13, pp. 2046–2053, 2002.
[13] H. R. Shaterian, F. Khorami, A. Amirzadeh,
R. Doostmohammadi, and M. Ghashang, “Preparation of
heterocyclic containing phthalazine skeleton: 2H Indazolo [2,
1-b] phthalazine-1, 6, 11 (13H)-triones,” Journal of the Iranian
Chemical Research, vol. 2, no. 1, pp. 57–62, 2009.
[26] S. Dixit, M. Patil, and N. Agarwal, “Ferrocene catalysed
heteroarylation of BODIPy and reaction mechanism studies
by EPR and DFT methods,” RSC Advances, vol. 6, no. 53,
pp. 47491–47497, 2016.
[27] L. Zheng, Y. Qiao, M. Lu, and J. Chang, “/eoretical inves-
tigations of the reaction between 1,4-dithiane-2,5-diol and
azomethine imines: mechanisms and diastereoselectivity,”
[14] M. Shekouhy and A. Hasaninejad, “Ultrasound-promoted
catalyst-free one-pot four component synthesis of 2H-

Heteroatom Chemistry
13
[43] H. Yahyaei, A. R. Kazemizadeh, and A. Ramazani, “Synthesis
and chemical shifts calculation of α-Acyloxycarboxamides
derived from indane-1,2,3-trione by DFT and HF methods,”
Chinese Journal of Structural Chemistry, vol. 31, pp. 1346–1356,
2012.
Organic
& Biomolecular Chemistry, vol. 13, no. 27,
pp. 7558–7569, 2015.
[28] A. Bekhradnia and P.-O. Norrby, “New insights into the
mechanism of iron-catalyzed cross-coupling reactions,”
Dalton Transactions, vol. 44, no. 9, pp. 3959–3962, 2015.
[29] D. Duca, G. La Manna, and M. Rosa Russo, “Computational
studies on surface reaction mechanisms: ethylene hydroge-
nation on platinum catalysts,” Physical Chemistry Chemical
Physics, vol. 1, no. 6, pp. 1375–1382, 1999.
[30] S. G. Smith and J. M. Goodman, “Assigning stereochemistry
to single diastereoisomers by GIAO NMR calculation: the
DP4 probability,” Journal of the American Chemical Society,
vol. 132, no. 37, pp. 12946–12959, 2010.
[31] Z. Yang, P. Yu, and K. N. Houk, “Molecular dynamics of
dimethyldioxirane C-H oxidation,” Journal of the American
Chemical Society, vol. 138, no. 12, pp. 4237–4242, 2016.
[32] P. E. Hansen and J. Spanget-Larsen, “Structural studies on
Mannich bases of 2-Hydroxy-3,4,5,6-tetrachlorobenzene. An
UV, IR, NMR and DFT study. A mini-review,” Journal of
Molecular Structure, vol. 1119, pp. 235–239, 2016.
[33] S. Demir, A. O. Sarioglu, S. Gu¨ler, N. Dege, and M. Sonmez,
“Synthesis, crystal structure analysis, spectral IR, NMR UV-
Vis investigations, NBO and NLO of 2-benzoyl-N-(4-chlor-
ophenyl)-3-oxo-3-phenylpropanamide with use of X-ray
diffractions studies along with DFT calculations,” Journal of
Molecular Structure, vol. 1118, pp. 316–324, 2016.
[34] S. K. Saha, A. Hens, N. C. Murmu, and P. Banerjee, “A
comparative density functional theory and molecular dy-
namics simulation studies of the corrosion inhibitory action
of two novel N-heterocyclic organic compounds along with a
few others over steel surface,” Journal of Molecular Liquids,
vol. 215, pp. 486–495, 2016.
[35] G. M. Anderson, I. Cameron, and J. A. Murphy, “Predicting
the reducing power of organic super electron donors,” RSC
Advances, vol. 6, no. 14, pp. 11335–11343, 2016.
[36] J. L. Tuttle and S. D. Wetmore, “Selecting DFT methods for
use in optimizations of enzyme active sites: applications to
ONIOM treatments of DNA glycosylases,” Canadian Journal
of Chemistry, vol. 91, no. 7, pp. 559–572, 2013.
[44] K. G. Vipin Das, C. Yohannan Panicker, B. Narayana,
P. S. Nayak, and B. K. Sarojini, “FT-IR, molecular structure,
first order hyperpolarizability, NBO analysis, HOMO and
LUMO and MEP analysis of 1-(10H-phenothiazin-2-yl)
ethanone by HF and density functional methods,” Spec-
trochimica Acta Part A: Molecular and Biomolecular Spec-
troscopy, vol. 135, pp. 162–171, 2015.
[45] S. Al-Saadi and N. Sundaraganesan, “/e spectroscopic (FT-
IR, FT-IR gas phase, FT-Raman and UV) and NBO analysis of
4-Hydroxypiperidine by density functional method,” Spec-
trochimica Acta Part A: Molecular and Biomolecular Spec-
troscopy, vol. 75, no. 3, pp. 941–952, 2010.
¨
[46] T. Koopmans, “Uber die Zuordnung von Wellenfunktionen
und Eigenwerten zu den Einzelnen Elektronen Eines Atoms,”
Physica, vol. 1, no. 1-6, pp. 104–113, 1934.
[47] A. Soltani, F. Ghari, A. D. Khalaji et al., “Crystal structure,
spectroscopic and theoretical studies on two Schiff base
compounds of 2,6-dichlorobenzylidene-2,4-dichloroaniline
and 2,4-dichlorobenzylidene-2,4-dichloroaniline,” Spec-
trochimica Acta Part A: Molecular and Biomolecular Spec-
troscopy, vol. 139, pp. 271–278, 2015.
˘
¨
[48] R. G. Pearson, “Chemical hardness and density functional
theory,” Journal of Chemical Sciences, vol. 117, no. 5,
pp. 369–377, 2005.
´
[49] F. J. Luque, J. M. Lopez, and M. Orozco, “Perspective on
“Electrostatic interactions of a solute with a continuum. A
direct utilization of ab initio molecular potentials for the
prevision of solvent effects,” >eoretical Chemistry Accounts,
vol. 103, pp. 343–345, 2000.
[50] K. Chandrasekaran and R. /ilak Kumar, “Structural, spec-
tral, thermodynamical, NLO, HOMO, LUMO and NBO
analysis of fluconazole,” Spectrochimica Acta Part A: Molec-
ular and Biomolecular Spectroscopy, vol. 150, pp. 974–991,
2015.
[37] A. D. Becke, “Density-functional thermochemistry. III. /e
role of exact exchange,” >e Journal of Chemical Physics,
vol. 98, no. 7, pp. 5648–5652, 1993.
[38] M. J. Frisch, G. W. Trucks, and H. B. Schlegel, Gaussian 03,
Revision B03, Gaussian Inc., Pittsburgh, PA, USA, 2003.
[39] L. Shiri, D. Sheikh, A. Faraji, M. Sheikhi, and S. Katouli,
“Selective oxidation of oximes to their corresponding car-
bonyl compounds by sym-collidinium chlorochromate (S-
COCC) as a efficient and novel oxidizing agent and theoretical
study of NMR shielding tensors and thermochemical pa-
rameters,” Letters in Organic Chemistry, vol. 11, no. 1,
pp. 18–28, 2014.
[40] A. Soltani, M. T. Baei, M. Mirarab, M. Sheikhi, and E. Tazikeh
Lemeski, “/e electronic and structural properties of BN and
BP nano-cages interacting with OCN− : a DFTstudy,” Journal
of Physics and Chemistry of Solids, vol. 75, no. 10, pp. 1099–
1105, 2014.
[41] A. Frisch, A. B. Nielson, and A. J. Holder, GAUSSVIEW User
Manual, Gaussian Inc., Pittsburgh, PA, USA, 2000.
[42] S. Guidara, H. Feki, and Y. Abid, “Molecular structure, NLO,
MEP, NBO analysis and spectroscopic characterization of 2,5-
dimethylanilinium dihydrogen phosphate with experimental
(FT-IR and FT-Raman) techniques and DFT calculations,”
Spectrochimica Acta Part A: Molecular and Biomolecular
Spectroscopy, vol. 133, pp. 856–866, 2014.