Document Type : Original Research Article

Authors

1 Department of Chemistry, L.V.H. Arts, Science, and Commerce College, Panchavati, Nashik, India

2 Department of Chemistry, Arts, Science, and Commerce College, Manmad, Nashik, India

10.22034/ajca.2021.283003.1254

Abstract

In the present work, synthesis and DFT study of 2-(4-fluorophenyl)-5-phenyl-1,3,4-oxadiazole is reported. The 6-311++G (d,p) basis set was used to optimize the molecular structure of the title compound using the DFT/B3LYP method.The structural parameters, bond length, and bond angle were studied. The fundamental vibrational wavenumbers and intensities were computed, and the observed and calculated wavenumbers were found to be in excellent agreement.  In order to decide the reactivity and possible site for electrophilic and nucleophilic, Frontier molecular orbital (HOMO-LUMO) energies, global reactivity descriptors, molecular electrostatic potential as well as Mulliken charges were calculated using the same theory. The obtained results indicates that the compound possess good kinetic stability. The molecular electrostatic potential surface analysis shows that the nitrogen atom oxadiazole ring is the binding site for electrophilic attack.

Graphical Abstract

Molecular Structure, FT-IR Spectra, MEP and HOMO-LUMO Investigation of 2-(4-Fluorophenyl)-5-phenyl-1, 3,4-oxadiazole Using DFT Theory Calculations

Keywords

Introduction

Due to various remarkable biological and pharmacological properties, 1,3,4-oxadiazoles (C2H2N2O)  their  noteworthy class of compounds  have long piqued interest. Antitubercular [1], antimicrobial [2-3], anticancer [4], anti-inflammatory [5], anticonvulsant [6], analgesic [7], and insecticidal activities [8] are some of the prominent pharmacological applications of 1,3,4-oxadiazoles. Computational chemistry has recently drawn attention among researchers and scientists as a means of solving real problems in chemical, medicinal, biotechnology, and material science [9,11]. Computational chemistry is used in the designing of new drugs and materials to solve numerical problems [9,12-14]. Nowadays, resarchers use various computational programs to predict the molecular structure and physical properties of bioactive molecules [11-13]. The density functional theory (DFT) is a popular method for defining the structural and electronic properties of atoms and molecules [10,11] . The B3LYP functional and 6-311++G(d,p) basis set have been found to be the most typically used level of theory for DFT simulations in order to analyze various optical, spectral, and charge density properties of large and small molecules [15-17]. Many organic systems' vibrational spectra have been calculated using DFT, and the findings have shown to be encouraging. [18,20]. Molecular electrostatic potential  (MESP) is commonly used as a reactivity map to explain hydrogen bonding interactions, as well as sites for  electrophilic and nucleophilic reactions on organic molecules [21]. Very few reports have addressed theoretical computation of the 1,3,4-oxadiazole deivatives. This study presented a good tool to assess the theoretical insights into these biologically active compounds and thereby researchers can explore the molecular and spectroscopic properties. It has been reported that the B3LYP functional with 6- 311++G(d,p) basis set provides good agreement between the theoretical and experimental structural and spectroscopic data [8,16]. Therefore, in the present investigation, we employed the B3LYP functional with 6- 311++G(d,p) basis set for the investigation of stuctural and spectroscopic facets of the titled compound. As far as our knowledge goes, the theoretical and experimental (FT -IR, HOMO-LUMO) study of 2-(4-fluorophenyl)-5-phenyl-1,3,4-oxadiazole has  not been  reported. Therefore, in continuation of our research in the field of therotical study of organic componds [22-25], here we wish to report DFT study of 2-(4-fluorophenyl)-5-phenyl-1,3,4-oxadiazole. The DFT study was used to enlighten the theoretical determination of the optimized molecular geometries, HOMO-LUMO energy gap, MEP, chemical reactivity, and stability of the title compound by using DFT/ B3LYP method with 6- 311++G(d,p) basis set.

Experimental details

Physical measurements

Melting point was measured by using open capillary method and uncorrected. The FT-IR spectrum was measured at room temperature on the Schimadzu spectrometer in the region of 4000-400 cm-1. All chemicals were purchased from commercial suppliers.

Synthesis 2-(4-fluorophenyl)-5-phenyl-1, 3, 4-oxadiazole (FPPO)

4-Fluorobenzohydrazide (0.002 moles) with benzoic acid (0.002 moles) was dissolved in dry phosphorous oxychloride. The reaction mixture was then refluxed for 3 hours. The reaction mixture was then concentrated using a rotatory evaporator, and the resulting residue was quenched with ice water. The solid separated was filtered off, washed with water, and purified further by recrystallization with isopropanol to yield the 2-(4-fluorophenyl)-5-phenyl-1,3,4-oxadiazole as a white crystalline solid. The synthetic method and structure of the title compound are shown in Scheme 1.

Scheme 1. Synthesis of 2-(4-fluorophenyl)-5-phenyl-1,3,4-oxadiazole

Computational details

The Gaussian 03 software [26] was used to perform all calculations. The optimized geometrical parameters and vibrational frequencies of the compound were calculated using the DFT/ B3LYP [27,28] method and the basis set 6-311G++(d,p). To maintain equilibrium between empirical and theoretical harmonic frequencies, the scale factor 0.9613 [29] was used. The findings were analyzed with the aid of the gauss view 4.1 molecular visualisation software [30]. DFT method with the same basis set has been put forth for calculating Molecular electrostatic potential, Mulliken charges, electronic properties such as HOMO-LUMO energies and reactivity parameters.

Results and Discussion

Molecular geometry

All DFT calculations were performed in gas phase. Table 1 shows the relevant structural parameters of title molecule (FPPO) which have been obtained by DFT. The optimize structure of the FPPO molecule with the labeling of atoms are shown in Figure 1. No symmetry constraint has been noticed during geometry optimization. The molecular structure of the title FPPO molecule contains two phenyl rings attached to central oxadiazole core ring. The Para-fluoro substituted phenyl ring considered as PhI and unsubstituted ring attach to C9 carbon of central oxadiazole ring that is considered as PhII. The C-O bond length oxadiazole structures were found between 1.368 Å-1.366 Å. The C19-F26, C11-C12 and C9-C5 bond lengths are 1.352 Å, 1.456Å and 1.457 Å, respectively, and found within the normal range.  The optimized structure is found to be with C1 point group symmetry having its ground state energy of -823.67845783 a.u. If the dihedral angles between three rings are analyzed, we can see that they are on the same plane. The bond lengths of C11-N23 and C9-N22 bond is 1.298, showing a double bond character. The optimized bond length of in six member ring PhI is calculated in the range 1.402–1.386 Å, whereas it is slightly greater for another six membered ring PhII and found in the range 1.403–1.389 Å. In optimized structure, phenyl C-H bond lengths are observed within the range 1.083–1.084 Å.

Table 1. Some selected structural parameters of FPPO molecule calculated by DFT/B3LYP/6-311++G (d,p) methods

Figure 1. The molecular structures of FPPO molecule obtained by DFT/B3LYP/6-311G++ (d,p) method

Vibrational frequency assignment

Experimental IR spectrum is recorded in the region of 4000-500 cm-1 (Solid phase) and calculated vibrational spectrum in the gas phase. The title FPPO molecule contains total 27 atoms with 75 fundamental modes of vibration. Theoretical and experimental IR spectrum is shown in Figure 2. Table 2 shows some of the theoretical and experimental vibrations with intensity and their assignments. The stretching vibrations of the aromatic C-H ring are usually located between 3100 and 3000 cm-1. The C-H stretching vibrations of the title molecule are assigned to the measured frequencies in the range 3085-3045 cm-1. The experimental vibrational frequency appears in the range 3059 cm-1 of the IR spectrum showing good correlation with calculated frequency 3055 cm-1. The In-plane C-H bending vibrations for aromatic ring is experimentally observed at 1481,1409, 1278,1149,1076,1014 cm-1, showing good correlation with computed vibrations at 1465,1420,1281,1156,1076,1006 cm-1. Similarly, the out of plane vibrations for aryl rings observed at  964,835,775,692 cm-1 agreed with computed 967,826,756,682 cm-1 infrared vibrations. The identification of C=N stretching frequencies was a rather difficult task because of the mixing of vibrations. The C=C and C=N mixed stretching modes experimentally were observed at 1602, 1546 and 1481 cm-1 and by DFT method it was observed at 1584, 1560 and 1465 cm-1. In the fingerprint region of the FT-IR spectrum the C-O stretching vibration mode were observed at frequencies 1226 and 1149 cm-1, calculated at 1233 and 1156 cm-1, respectively. These vibrations are coupled with C-C in-plane bending modes and vibrations in the in-plane bending mode. The bands attributable to C-F stretching vibrations can be found in the vibrational spectra of the FPPO molecule over a broad frequency range of 1360-1000 cm-1. In this study, the C-F stretching mode of vibration for FPPO was determined to be 1197 cm-1, but this band was not observed experimentally. 

Figure 2. Experimental and Theoretical IR spectrum of FPPO molecule

Table 2. The observed FT-IR and calculated (B3LYP/6-311++G level) frequencies along with their selected assignments of the FPPO molecule

Frontier molecular orbitals and Global Chemical Reactivity Descriptors

Descriptors of global reactivity are used to forecast global reactivity patterns. Frontier molecular orbitals are the highest occupied and lowest unoccupied molecular orbitals, respectively. Figure 3 shows a HOMO-LUMO plot of the title compound (FPPO). The calculated HOMO and LUMO energies in the gas phase are - 6.5743 eV and - 2.0928 eV, respectively. The energy gap of the title compound, on the other hand, is 4.4815 eV. Various chemical reactivity parameters were calculated using the HOMO-LUMO energies. The HOMO represents the outermost orbital filled by electrons and is directly related to the ionization potential while the LUMO can be thought as the first empty innermost orbital unfilled by electron and is directly related to the electron affinity. Using Koopmans' theorem and equations 1-4, The parameters ionisation potential (I), electron affinity (A), chemical hardness (ɳ), and chemical softness (S), electronic chemical potential (μ) as well as global electrophilicity index (ω) were calculated [31-35].

ɳ = ½ (I – A)         (1)

S = 1/η                  (2)

μ = -½ (I+A)         (3)

ω = μ2 / 2η            (4)

The frontier molecular energy gap aids in determining the molecule's chemical reactivity and stability. Table 3 shows HOMO, LUMO energies and global reactivity parameters, the global hardness (η) of 2.2407 eV, Chemical Softness (S) 0.4462 eV, electrophilicity Index (ω) 4.1904 eV, chemical potential (μ) - 4.3335 eV. Compaired with previously published literature [36-40], these calculated results indicated that the compound possess good kinetic stability.

Figure 3. Frontier molecular orbitals surface and energy gap for FPPO Molecule

Table 3. The HOMO-LUMO energys and reactivity descriptor values of the FPPO Molecule are computed in the gas phase

Mulliken atomic charges and molecular electrostatic potential

Mulliken atomic charges are useful in determining the chemical reactivity of compounds. Table 4 presents the Mulliken atomic charges of various atoms in the title molecule. The C12 and C5 atoms, as shown in Table 4, have the highest positive charge of all carbon atoms and are thus predicted to be the target of nucleophilic attack on the title compound. Of all carbon atoms, the C4 and C14 atoms have a higher negative charge. The atoms of oxygen, nitrogen, and fluorine have a negative charge. Hydrogen atoms all have a positive charge.

Table 4. Mulliken atomic charges at the B3LYP/6-311++G (d, p) level for the title compound

The molecular electrostatic potential surface (MESP) plot is a representation of electrostatic potential plotted on a constant electron density surface. The chemical reactivity of sites is determined by the molecular electrostatic potential. The polar nature of the title compound (FPPO) is indicated by its dipole moment of 3.3514 Debye. The MESP method was used to predict the presence of reactive sites in the FPPO molecule for electrophilic and nucleophilic attack. MESP for the title compound are shown in Figure 4. Different colours on the MESP plot reflect different electrostatic potential values: Red, blue, and green regions represent maximum electrophilic reactivity, nucleophilic reactivity, and zero electrostatic potential, respectively. Decrease in potential occurs as blue > green > yellow > orange > red. The MESP of the title molecule clearly demonstrates the presence of a large negative potential area around nitrogen atoms, which is coloured red, and where electrophilic attack can occur. The hydrogen atoms have the most positive electrostatic potential, while the rest of the molecule appears to be almost neutral.

Figure 4. The MESP map of the title compound (FPPO)

Conclusion

In this paper, we conducted an experimental and theoretical vibrational study of 2-(4-fluorophenyl)-5-phenyl-1,3,4-oxadiazole. The DFT (B3LYP) system 6-311++G(d,p) basis set was used to determine the molecular geometry parameters and wavenumbers (Vibration spectra) for the title compound in the ground state. The experimental vibrational frequencies were found to be in strong agreement with the measured vibrational frequencies. This comparison of experimental and theoretical spectra revealed valuable details about the computational method's ability to characterise vibrational modes. The title compound has a dipole moment of 3.3514 Debye, which implies that it is polar. The nitrogen atom on oxadiazole ring was discovered to be the binding site for electrophilic attack using molecular electrostatic potential surface analysis. The energy difference between the HOMO, LUMO and global chemical reactivity parameters revealed that the compound is kinetically stable.

Acknowledgements

The Authors acknowledge the KTHM College, Nashik for FT-IR spectral analysis. The authors also would like to thank Principal of MGV’s L.V.H. Arts, Science and Commerce College, Panchvati, Nashik for permission and providing necessary research facilities. Authors are also grateful to Ex Professor Dr. A. B. Sawant for Gaussian study. Dr. Aapoorva Prashant Hiray, Coordinator, MG Vidyamandir Institute, is gratefully acknowledged for Gaussian package.

Disclosure statement

No potential conflict of interest was reported by the authors.

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