Synthesis and Theoretical Calculations of 2-(p-Tolyl)-2,3- Dihydro-1H-Perimidine using Density Functional Theory

In the present study, 2-(p-tolyl)-2,3-dihydro-1H-perimidine (TDHP) is synthesized from 1,8-naphthalenediamine and 4-methylbenzaldehyde by embedding a one-carbon unit between the nitrogen followed by ring closure using green chemistry approach. 1H NMR and 13C NMR spectral techniques were used to validate the structure of the TDHP. The synthesized perimidine TDHP is studied using density functional theory (DFT) to provide valuable insights into structural, chemical, and thermochemical study.The structural and chemical properties of TDHP were computed using the DFT method on the B3LYP/6-311G(d,p) basis package. Bond lengths were predicted from the optimized molecular structure, and the physical and chemical properties of the molecules were inferred as a consequence. The HOMO and LUMO are computed, and quantum chemical parameters are determined using electronic energies. The calculated HOMO-LUMO energy gap is 4.25 eV indicating charge transfer phenomenon within the molecule. The electron density and chemical behaviour of the TDHP was predicted using Mulliken atomic charges and the molecular electrostatic surface potential plot. Amongst all carbon atoms, the C8 carbon as more positive and C27 as more negative carbon atoms. The high global electrophilicity index suggests electrophilic character of the TDHP. The harmonic vibrational frequencies were used to measure total energy, total molar entropy, and molar heat capacity. CONTACT Vishnu A. Adole vishnuadole86@gmail.com Department of Chemistry, Mahatma Gandhi Vidyamandir’s Arts, Science and Commerce College, Manmad, Nashik-423 104, India. (Affiliated to SP Pune University, Pune). © 2021 The Author(s). Published by Enviro Research Publishers. This is an Open Access article licensed under a Creative Commons license: Attribution 4.0 International (CC-BY). Doi: http://dx.doi.org/10.13005/msri/180109 Article History Received: 03 March 2020 Accepted: 12 April 2021


Introduction
Perimidine is a tri-cyclic heterocycle comprising two nitrogen atoms at the first and third positions, which enhances pi-electrons' delocalization to the naphthalene ring from the fused heterocyclic ring. Perimidines' biological behaviour has been the topic of numerous journal entries in recent years. Perimidines are robust motifs and an interesting family of N-heterocycles that have advanced significantly in recent years as a result of their wide range of uses in life sciences, medicine, and industrial research. Their way to interact molecularly with protein molecules, form complexes with metal, and behave differently in different light wavelengths renders themselves increasingly enticing for potential use.Perimidines are of great interest to researchers because of their broad variety of biological activities. 1,2 The biological profile of several perimidine hybrids is found to be explored in numerous applications such as Pd(II) complexes derived from perimidine ligand for in-vitro antimicrobial applications, 3 antioxidant properties of transition metal complexes of perimidine ligand, 4 anti-inflammatory studies of transition metal complexes of 1H-perimidine derivatives, 5 2-phenylazonaphtho [1,8-ef] [1,4] diazepines and 9-(3-arylhydrazono) pyrrolo [1,2-a] perimidines as antitumor agents, 6 oxo-7H-benzo [e] perimidine-4-carboxylic acid derivatives as potent, nonpeptidecorticotropin releasing factor (CRF) receptor antagonists, 7 and 3-Chloro-1-(4-perimidine methylcarbonylamino)-4-phenylazetidin-2-one for antibacterial and antifungal activities. 8 Besides, 1-alkylperimidineruthenium (II) complexes were used for catalytic applications, 9 N-xylyl-N′-methylperimidinecarbene iridium complexes as catalysts for C-H activation and dehydrogenativesilylation, 10 perimidin-2-ylidene rhodium(I) complexes for transfer hydrogenation reaction, 11 Perimidine based synthetic receptors for identification of cupric ionin water solution, 12 2,3-dihydroperimidine derivatives for lubricants, 13 etc.

Graphical abstract
The DFT approach with the B3LYP functional has been shown to predict theoretical properties that are in good agreement with experimental spectroscopic results. [42][43][44][45] Using the B3LYP functional with a 6-311G(d,p) basis set, the assignment of absorption bands and, as a result, the prediction of electronic and chemical properties of molecules is found to be accurate. 46,47 Energized by all above mentioned aspects, in the present study, we have synthesized, characterized and studied 2-(p-tolyl)-2,3-dihydro-1H-perimidine using DFT method with B3LYP/6-311G(d,p) basis set.This is first report on DFT study of the TDHPcompound. For the TDHP molecule, no work on DFT analysis for the exploration of structural, electronic, and chemical parameters has been done to date.Structural parameters using optimized molecular structure have been obtained.
The optimized structure provides the information of geometrical parameters, stability of the molecule and also polarity. With the help of geometry optimization, HOMO-LUMO energies are computed and these are further used for the determination of electronic and global reactivity parameters. I have predicted the electronic properties such asionization potential energy (I)electron affinity (A) and global reactivity attributes such as hardness (η), softness (S), electronegativity (χ), chemical potential (μ) and electrophilic index (ω) with the help of HOMO-LUMO energies.The band gap energy and frontier molecular orbitals (FMOs) are established and examined. The molecular electrostatic surface potential is established by using optimized structure and being used to locate sites for electrophilic and nucleophilic attacks.

Materials and Methods General Remarks
The 1,8-diamino naphthalene (Purity: 99%, Make: sigma Aldrich) and p-Tolualdehyde (Purity: 98%, Make: Alfa aesar) chemicals were purchased from Virion Enterprises, Mumbai. The chemicals were used exactly as they were obtained, with no further purification needed.Melting point was determined in open capillary and uncorrected. 1 H NMR and 13 C NMR spectra were recorded with a Bruker using DMSO-d6 solvent on 400 MHz NMR Spectrometer. Thin-layer chromatography using aluminium sheets with silica gel 60 F254 (Merck) was used to track the completion of the reaction.

Synthesis of TDHP
In the past, the p-TSA was employed for the synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives. 48 Based on this we tried the synthesis of TDHP using p-TSA using 2 mol% catalyst dose and to our credit, we got good results in terms of synthetic efficiency. We did not switch our attention for optimizing the reaction conditions as our main goal of the present research is study of structural, electronic and chemical nature of the TDHP molecule.In a standard reaction procedure, a mixture containing naphthalene-1,8diamine (1, 0.01mol), p-toluene benzaldehyde (2, 0.01 mol) and p-TSA (2 mol%) in ethanol (5 mL) were taken in a conical flask and stirred at room temperature for 30 minute on magnetic stirrer. After completion of the reaction (monitored by TLC), the crude product was obtained simply filtration and the it was purified by recrystallization to provide the perimidine derivative (3): 2-(p-tolyl)-2,3-dihydro-1Hperimidine (Scheme 1). The physicochemical and spectral data of title compound is given in Table 1.

Computational Details
DFT measurements of a TDHP molecule were conducted using the Gaussian 03 software package. 49 The molecular structure of the TDHPmolecule in the ground state was optimized using the density functional theory (DFT/B3LYP) 50, 51 with the 6-311G(d,p) basis set. 52,53 All the quantum chemical calculations for the TDHP compound were performed at B3LYP/6-311G(d,p) level and corresponding molecular drawing was done with the aid of the Gauss View 4.1.2 visualization programme. 54 Thermochemical data were obtained using harmonic vibrational frequencies.

Results and Discussion Geometrical Parameters
The optimized molecular structure of the title molecule is given in Figure 1. Table 1 shows the optimized geometric parameter bond lengths by B3LYP with the 6-311G(d,p) basis set. The B3LYP method is well known for predicting geometrical parameters that are closer to experimental results, as discussed in the literature. 55 B3LYP/6-311G(d,p) is taken into consideration for these purposesin the present discussion.The information about bond lengths is very crucial to get insights into inter and intra molecular interactions, hydrogen bonding effects and also chemical reactivity patterns. 56 59 The global reactivity parameters like chemical hardness (η), chemical softness (S), chemical potential (μ) and electrophilicity index (ω) are calculated using HOMO-LUMO energies. The calculated chemical hardness and chemical softness values are 2.12 eV and 0.47eV -1 respectively.These two values are critical in determining the polarizability of the TDHP compound. The existence of intermolecular interactions and chemical reactivity may be predicted by comparison with other molecules. The electrophilicity index value in the title molecule is 1.75 eV.The electrophilicity index is greater than 1.5 eV that indicates the TDHPcompound could accept the electrons. 58 The chemical potential value is 2.72 eV.

Mulliken Atomic Charges
Mulliken charges for the TDHP molecule are determined using the B3LYP/6-311G(d,p) method and are described in Figure 3 and Table 3 to estimate the net atomic populations in the TDHP molecule. Mulliken atomic charges calculation remains essential in the implementation of quantum chemical calculations to molecules because atomic charges impact several attributes of molecules. The two nitrogen atoms of the title molecule are found to be most negative in terms of Mulliken atomic charge with -0.610591 and -0.596207Mulliken atomic charge values for N33 and N35 atoms. The C8 atom is the most positive atom with Mulliken atomic charge value of 0.289643. All hydrogen atoms in the title molecule are positive in terms of Mulliken atom charge.

Fig. 2: Frontier molecular orbitals and HOMO-LUMO energy gap
Frontier Molecular Orbital Analysis HOMO and LUMO are called as frontier molecular orbitals (FMOs) and very crucial for assessing a molecule's reactivity and stability. HOMO and LUMO are linked with electron-donating and electronaccepting capabilities respectively. The narrower the energy difference between HOMO and LUMO, the more stable a molecule becomes. A decrease in stability, polarizability, and electron transport in a molecule occurs as the HOMO-LUMO energy gap is increased. Since they relate to ionization potential energy and electron affinity, respectively, the HOMO

Molecular Electrostatic Surface Potential and Thermochemistry Analysis
The molecular electrostatic surface potential (MESP) plotof the TDHP molecule given in Figure4 is used to investigate the chemical reactivity of the title molecule, and it is plotted over the optimized electronic structure of the title compound using density functional B3LYP level with 6-311G(d,p) basis collection. Since it was established in space around a molecule by the charge distribution, the MESP plot is quite valuable in studying the reactive sites for nucleophilic and electrophilic attacks, hydrogen bonding interactions and also in the biorecognition processes. Different colours represent different electrostatic potential values: red symbolizes negative electrostatic potential, blue denotes positive electrostatic potential, and green depicts less positive electrostatic potential.
In the title molecule the negative potential is around nitrogen atom and also around naphthalene ring system indicating high electron density which indicatesits reactivity as nucleophile. The highest positive potential is found around hydrogen atoms attached to the nitrogen atoms. The hydrogen atoms are expected to react with bases to form anions.
The p-tolyl ring system possesses less positive electrostatic potential values. The statistical analysis thermodynamic functions: total thermal energy, heat capacity, and entropy for the TDHP compound were obtained from the theoretical harmonic frequencies and described in Table 4 based on vibrational analysis at the B3LYP/6-311G(d,p) stage.

Conclusion
The TDHP compound was synthesized using green chemistry approach and 1 H and 13 C NMR spectroscopy was used to affirm the molecular structure of the synthesised compound TDHP. DFT calculations were used to determine the molecular structural parameters, HOMO-LUMO analysis, MESP plot, Mulliken atomic charges, and thermodynamic properties of the title compound for optimized geometry. The geometry was optimised using the DFT/B3LYP/ method with the 6-311G(d,p) basis set without any symmetry constraints. According to the optimized molecular structure and bond length details, C1-C2 and C7-C10 bonds are more vulnerable to electrophilic attack. N35 was revealed to be more reactive to acidic reagent. The two nitrogen atoms in the title molecule are the most negative and on the other hand hydrogen atoms in the title molecule are positivein terms of Mulliken atomic charge. According to MESP, negative potential around the nitrogen atom and even around the naphthalene ring structure in the title molecule shows a high electron density, suggesting its reactivity as a nucleophile. Besides, some thermochemical insights are provided. We conclude that the results of this analysis will allow for further research into the physical and chemical properties of the TDHP and related perimidine derivatives.