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

/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, H NMR, C NMR, mass spectra, and elemental analyses. /e IR spectra data and H NMR and C 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.


Materials and Methods
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 1 H NMR and 13 C NMR spectra were measured (CDCl 3 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. [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(NO 3 ) 2 .2H 2 O (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 viscous residue was purified by a preparative layer chromatography (silica gel; petroleum ether-ethyl acetate (8 : 2)). e solvent was removed under a reduced pressure and the products 5a-c were obtained.

Results and Discussion
e three-component reaction between 3-nitro phthalhydrazide (6), dimedone (3), and aromatic aldehydes (4) proceeded very smoothly and cleanly in the presence of a catalytic amount of ZrO(NO 3 ) 2 .2H 2 O at reflux conditions in ethanol and afforded the corresponding 1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione derivatives (5a-c) in high yields (Scheme 1 and Table 1), and no undesirable side reactions were observed. A mechanistic rationalization for this reaction is provided in Scheme 2. e structures of the products were deduced from their IR, 1 H NMR, 13 C NMR, mass spectra and elemental analyses. For example, the 1 H NMR spectrum of 5a exhibited distinct signals arising from two CH 3 Scheme 1: ree-component reaction of 3-nitrophthalic anhydride, hydrazine monohydrate, dimedone, and aromatic aldehydes (see Table 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 frequencies are provided in Tables 2-4. e harmonic frequencies 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].
For the title compound (5a), the strong band at 3376 cm − 1 in the FT-IR spectrum is assigned as v C=O mode.
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 experimental data was investigated. A small difference between the experimental and calculated vibrational modes was observed.
is difference might have been due to intermolecular hydrogen bonding formation. Also, the experimental results belong to the solid phase while theoretical calculations belong to the isolated gaseous phase.
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 (R 2 ) for compounds at HF/3-21G, B3LYP/ 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.

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 reflected the chemical reactivity of the molecule [43]. In addition, 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 electrondonating 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 Heteroatom Chemistry 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       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 potential, 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 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 potential 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, respectively). e high value for 5c was due to its asymmetric character.

3.2.4.
ermodynamic Analysis. e total energy of a molecule consists of the sum of translational, rotational, vibrational, and electronic energies. e statistical thermochemical analysis of title compounds is carried out considering the molecule to be at room temperature of 25°C and 1 atmospheric pressure. e thermodynamic parameters such as zero-point vibrational energy, rotational constant, 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, compounds 5a and 5b have maximum stability compared to compound 5c due to formation of intramolecular hydrogen bonding.

Molecular Electrostatic Potential (MEP).
e molecular electrostatic potential (MEP) was calculated by the B3LYP/6-311+G (d) level. e MEP is related to the electronic density and is a very useful descriptor in understanding 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 indicates the maximum of electrostatic potential, and it acts in the opposite manner. 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 nitrogenbonded oxygen atoms in the NO 2 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 activity. 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 attraction. As such, these sites provide information about the regions where the compounds can have strong intermolecular interactions.

Conclusion
In the present study, the three-component reaction between 3-nitrophthalic anhydride, hydrazine monohydrate, dimedone, and aromatic aldehydes in the presence of a novel catalytic amount of ZrO(NO 3 ) 2 .2H 2 O to produce 1Hindazolo[1,2-b]phthalazine-1,6,11(13H)-trione derivatives was reported. e reported method offers a mild and efficient procedure for the preparation of these compounds. ese compounds of the products were confirmed by IR, 1 H NMR, 13 C NMR, mass spectra, and elemental analyses. e IR spectra data and 1 H NMR and 13 C NMR chemical shift 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 experimental and theoretical results. Frontier molecular orbitals (FMOs), total density of states (DOS), and molecular electrostatic potential (MEP) of the title compounds were investigated through theoretical calculations.

Data Availability
No data were used to support this study.