Synthesis, crystal structure, DFT and Hirshfeld surface analysis of 4-fluoro-N-(1,3-dioxoisoindolin-2-yl)benzamide European Journal of Chemistry 14 (1) (2023) 1-8 European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2023 The Authors – Atlanta Publishing House LLC – Printed in the USA. This work is published and licensed by Atlanta Publishing House LLC – CC BY NC – Some Rights Reserved. https://dx.doi.org/10.5155/eurjchem.14.1.1-8.2335 European Journal of Chemistry View Journal Online View Article Online Synthesis, crystal structure, DFT and Hirshfeld surface analysis of 4-fluoro-N-(1,3-dioxoisoindolin-2-yl)benzamide Ramakrishnan Elancheran *, Balakrishnan Karthikeyan , Subramanian Srinivasan , Kuppusamy Krishnasamy and Senthamaraikannan Kabilan * Department of Chemistry, Annamalai University, Chidambaram-608002, Tamil Nadu, India * Corresponding author at: Department of Chemistry, Annamalai University, Chidambaram-608002, Tamil Nadu, India. e-mail: srielancheran@gmail.com (R. Elancheran), profdrskabilanau@gmail.com (S. Kabilan). 10.5155/eurjchem.14.1.1-8.2335 Received: 15 August 2022 Received in revised form: 10 November 2022 Accepted: 15 November 2022 Published online: 31 March 2023 Printed: 31 March 2023 The 4-fluoro-N-(1,3-dioxoisoindolin-2-yl)benzamide was synthesized by the reaction of 4- fluorobenzohydrazide with phthalic anhydride in acetic acid. The compound was characterized by analytical instruments like FT-IR and NMR. The three-dimensional structure of the title compound was further confirmed by single-crystal X-ray diffraction study. In addition to the experimental study, theoretical calculations were performed to explore the molecular structure in order to analyze experimental and theoretical findings. The title compound crystallizes in the monoclinic space group P21/n as determined by the X-ray diffraction investigation, crystal data for C15H9FN2O3·H2O: a = 14.094(6) Å, b = 7.248(3) Å, c = 14.517(6) Å, β = 105.116(14)°, V = 1431.6(10) Å3, Z = 4, T = 298(2) K, μ(MoKα) = 0.112 mm-1, Dcalc = 1.402 g/cm3, 37521 reflections measured (4.684° ≤ 2Θ ≤ 60.6°), 4225 unique (Rint = 0.0517, Rsigma = 0.0311) that were used in all calculations. The final R1 was 0.0537 (I > 2σ(I)) and wR2 was 0.1501 (all data). The N-H···O and O-H···O hydrogen bonds linking molecules in the crystal form a three-dimensional framework structure. The electronic states and molecular properties of the title compound were determined using computational studies, like density functional theory and Hirshfeld surface analysis. DFT Synthesis Benzamide Single crystal XRD HOMO/LUMO energies Hirshfeld surface analysis Cite this: Eur. J. Chem. 2023, 14(1), 1-8 Journal website: www.eurjchem.com 1. Introduction The 4-fluorobenzamide group has a wide range of pharma- cological properties, including anti-inflammatory [1], analgesic [1], anticancer [2], and antidiabetic activities [3], and are also well known for having significant bioactive frameworks. Similarly, isoindoline derivatives exhibit anti-inflammatory [4], anticancer [5-7], antiviral [8,9], antibacterial [9], anti- Alzheimer’s agents [10], and anticonvulsant activities [11]. It has been used in Structure Activity Relationship (SAR) investi- gations [12] and as a potential material for Organic Light- Emitting Diode (OLED) to substitute isoindolines with carboxy- lic acid groups. The carbamide group has anticonvulsant [13], antidepressant [13], and anti-human immunodeficiency virus (HIV) activities [14]. The title compound, 4-fluoro-N-(1,3-dioxo isoindolin-2-yl)benzamide, was investigated as part of our ongoing research on derivatives of acetamide and isoindoline [15,16]. The isoindoline and 4-fluorobenzamide moieties are present in the chemical structure of 4-fluoro-N-(1,3-dioxoiso indolin-2-yl)benzamide which was synthesized and the pure crystalline compound obtained was analyzed using FT-IR, 1H NMR, and 13C NMR spectroscopic techniques. The crystal structure of 4-fluoro-N-(1,3-dioxoisoindolin-2-yl)benzamide was acquired using a single-crystal X-ray diffractometer. Theoretical calculations, including DFT and Hirshfeld surface analysis, were also used to obtain molecular surfaces and opti- mum geometry of the structure, and contacts involved in the packing of the crystals. 2. Experimental 2.1. General Without further purification, all of the reagents and solvents were used after purchasing them from Sigma-Aldrich. Merck silica gel 60F254 precoated aluminum plates were used for the thin layer chromatography (TLC) analysis, which was used to monitor the reaction. On a Thermo Nicolet FT-IR Model iS5 spectrophotometer, KBr discs were used to record FT-IR (Fourier transform infrared) spectra in cm-1. Using a Bruker 400 MHz Nuclear Magnetic Resonance (NMR) instrument, 1H and 13C NMR spectra were captured in CDCl3. The chemical shift (δ) values are given in parts per million (ppm) with tetramethyl silane as the internal standard. Peak multiplicities are expres- sed using the following symbols: s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublet; br, broad; br s, broad singlet; m, multiplet. ABSTRACT RESEARCH ARTICLE KEYWORDS https://dx.doi.org/10.5155/eurjchem.14.1.1-8.2335 https://www.eurjchem.com/ https://dx.doi.org/10.5155/eurjchem.14.1.1-8.2335 mailto:srielancheran@gmail.com mailto:profdrskabilanau@gmail.com http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.14.1.1-8.2335&domain=pdf&date_stamp=2023-03-31 2 Elancheran et al. / European Journal of Chemistry 14 (1) (2023) 1-8 2023 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.14.1.1-8.2335 Table 1. Crystal data and details of the structure refinement for compound 4. Parameters Compound 4 Empirical formula C15H9FN2O3·H2O Formula weight (g/mol) 302.26 Temperature (K) 298(2) Crystal system Monoclinic Space group P21/n a, (Å) 14.094(6) b, (Å) 7.248(3) c, (Å) 14.517(6) β (°) 105.116(14) Volume (Å3) 1431.6(10) Z 4 ρcalc (g/cm3) 1.402 μ (mm-1) 0.112 F(000) 624.0 Crystal size (mm3) 0.31 × 0.27 × 0.19 Radiation MoKα (λ = 0.71073) 2Θ range for data collection (°) 4.684 to 60.6 Index ranges -19 ≤ h ≤ 19, -10 ≤ k ≤ 10, -20 ≤ l ≤ 20 Reflections collected 37521 Independent reflections 4225 [Rint = 0.0517, Rsigma = 0.0311] Data/restraints/parameters 4225/0/207 Goodness-of-fit on F2 1.045 Final R indexes [I≥2σ (I)] R1 = 0.0537, wR2 = 0.1239 Final R indexes [all data] R1 = 0.1072, wR2 = 0.1501 Largest diff. peak/hole (e.Å-3) 0.14/-0.14 Scheme 1. Synthesis of 4-fluoro-N-(1,3-dioxoisoindolin-2-yl)benzamide (4). 2.2. Synthesis To a solution of 4-fluorobenzoic acid (1 mmol) in ethanol (15 mL), a catalytic amount (3 mL) of concentrated H2SO4 was gradually added at room temperature, which was then refluxed for 16 hours while stirred. After the mixture was cooled, the ethanol was removed and the mixture was concentrated in a vacuum. The reaction mixture was diluted with ethyl acetate (30 mL) and then washed with saturated NaHCO3 and cold water, followed by separating the organic layer. The mixed organic layer was brine-washed, dried over anhydrous Na2SO4, concentrated, and vacuum-dried for 12 hours. Ethyl 4-fluoro- benzoate (1 mmol) was refluxed with hydrazine hydrate (2 mL) for one hour. Upon completion of the reaction, the reaction mixture was quenched with water and extracted with ethyl acetate. The combined organic layer was washed with a brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure [17]. Subsequently, phthalic anhydride was added to a 4-fluorobenzohydrazide solution in acetic acid and refluxed for 12 hours. The reaction mixture was placed over the crushed ice once the reaction had finished, as determined by TLC. To obtain the pure product, the precipitate from the ethanol was filtered, dried and recrystal- lized from the chloroform and methanol solvent mixture (1:1 ratio) (Scheme 1). 4-Fluoro-N-(1,3-dioxoisoindolin-2-yl)benzamide (4): FT-IR (KBr, ν, cm-1): 3078, 2982, 2822 (Ar. CHstr.), 1670 (-CO-NHstr.), 1600 (NHbend), 1508, 1423 (C=Carom), 1312, 1289, 1224 (C– Hbend). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 8.08-8.05 (m, 4H, Ar-H), 7.98-7.93 (m, 4H, Ar-H), 7.31 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6 & CDCl3, δ, ppm): 170.3 (C=O), 168.7 (NH-C=O), 157.9 (C-F), 140.6 (C-Ar), 135.8 (C-Ar), 134.7 (C-Ar), 131.1 (C- Ar), 129.4 (C-Ar), 121.3 (C-Ar). HRMS (ESI, m/z) calculated C15H9FN2O3: 284.05972; [M–H]-, Found: 283.26868. 2.3. X-ray structure determination On a Bruker D8 Quest diffractometer, a single-crystal X-ray diffraction (SC-XRD) experiment was carried out to determine the structure of 4-fluoro-N-(1,3-dioxoisoindolin-2-yl)benza- mide. A proper crystal was mounted onto a micro loop using Fomblin oil. MoKα radiation (λ =0.71073 Å) was used in this study. Omega and phi-scan modes were used to record the intensities at different diffraction angles. SC-XRD data were collected at room temperature. The data was collected using APEX3 software and APEX3 was also used to index reflection data and obtain unit cell parameters [18,19]. The crystal and structure refinement data are presented in Table 1. Elancheran et al. / European Journal of Chemistry 14 (1) (2023) 1-8 3 2023 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.14.1.1-8.2335 Table 2. Experimental and theoretical bond lengths of compound 4. Bond Bond lengths (Å) Bond Bond lengths (Å) XRD DFT (B3LYP/6-311G(d,p)) XRD DFT (B3LYP/6-311G(d,p)) F1-C9 1.360(2) 1.39790 C3-C11 1.378(2) 1.40350 O1-C5 1.2182(19) 1.24311 C5-C6 1.482(2) 1.48736 O2-C10 1.202(2) 1.23057 C6-C7 1.380(2) 1.40395 O3-C4 1.190(2) 1.23075 C6-C14 1.376(2) 1.40472 N1-N2 1.3759(19) 1.37511 C7-C8 1.373(3) 1.39282 N1-C4 1.400(2) 1.42357 C8-C9 1.343(3) 1.38819 N1-C10 1.377(2) 1.42434 C9-C15 1.357(3) 1.38679 N2-C5 1.351(2) 1.39032 C10-C11 1.481(2) 1.48283 C1-C2 1.381(3) 1.40296 C11-C12 1.371(2) 1.38688 C1-C13 1.358(3) 1.40105 C12-C13 1.384(3) 1.40300 C2-C3 1.377(2) 1.38689 C14-C15 1.385(3) 1.39561 C3-C4 1.476(2) 1.48309 Figure 1. The ORTEP diagram of compound 4 showing the atom-labeling scheme. Figure 2. Intermolecular H-bonding interactions of compound 4. 2.4. Computational methodology The optimized structure was derived by quantum mecha- nical calculations (Gaussian 09W [20] software package, followed by the density functional group theory (DFT) B3LYP [21,22] with 6-311G(d,p) basis set). The geometric parameters obtained from the SC-XRD study were compared with those determined theoretically. The Mulliken charges, the HOMO- LUMO energy gap, and the molecular electrostatic potential (MEP) of compound 4 were calculated and they were visualized and investigated by GaussView 5.0 [23]. The CrystalExplorer3.1 program has been used to perform the Molecular Hirshfeld surfaces, fingerprint plots and crystal voids evaluation [24-26]. The contacts that are short (red), intermediate (blue), and long (white) in comparison to the sum of van der Waals interactions were shown by color coding on the dnorm surface. Additionally, analyses using Shape-index, curvedness, electrostatic potential, and framework analysis have been performed [24]. 3. Results and discussion 3.1. Chemistry The 4-fluorobenzohydrazide was synthesised using the commercially available 4-fluoro benzoic acid by esterification, followed by hydrazine hydrate reaction. Further, to a solution of 4-fluorobenzohydrazide in acetic acid, phthalic anhydride was added and refluxed for 12 h. The completion of the reaction was monitored by TLC. The contents obtained were poured on crushed ice. The precipitate was filtered, dried and purified from ethanol to obtain the pure product as depicted in Scheme 1. The title compound (4) has nine protons, according to 1H NMR analysis. Around δ 7.93 to 8.08 ppm, phenyl protons were detected as multiplets. Compound 4 includes a variety of carbon atom signals, including aromatic carbon (C=O and C-F units) according to the 13C NMR results. At δ 121.3, 129.4, 131.1, 134.7, 135.8, and 140.6 ppm, aromatic carbons were observed. The presence of C=O is shown by the carbon signals at δ 168.7 and 170.3 ppm. Furthermore, FT-IR showed the appropriate absorption bands for compound 4 as well. 3.2. Crystal structure analysis Compound 4 was crystallized under the monoclinic system with space group P21/n. The ORTEP diagram for compound 4 is shown in Figure 1. The crystallographic parameters for compound 4 are shown in Table 1. The geometrical parameters (bond length, bond angle and dihedral angle) of compound 4 are also given in Tables 2-4. Table 5 contains the details of hydrogen bonding. Furthermore, the main hydrogen bonding interactions observed in compound 4 are depicted in Figure 2. The obtained bond lengths and angles were compared with the DFT calculations and the obtained data remain within the usual limits [27,28]. 4 Elancheran et al. / European Journal of Chemistry 14 (1) (2023) 1-8 2023 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.14.1.1-8.2335 Table 3. Experimental and theoretical bond angles of compound 4. Bond Bond angles (°) Bond Bond angles (°) XRD DFT (B3LYP/6-311G(d,p)) XRD DFT (B3LYP/6-311G(d,p)) N2-N1-C4 122.60(15) 123.00 C14-C6-C7 118.25(16) 119.56 N2-N1-C10 123.93(14) 123.44 C8-C7-C 121.26(17) 120.53 C10-N1-C4 112.99(14) 112.62 C9-C8-C7 118.39(18) 118.23 C5-N2-N1 118.62(14) 119.74 C8-C9-F1 118.58(19) 118.53 C13-C1-C2 120.84(18) 120.99 C8-C9-C15 123.22(18) 123.03 C3-C2-C1 117.5(2) 117.69 C15-C9-F1 118.2(2) 118.43 C2-C3-C4 130.01(18) 129.65 O2-C10-N1 124.20(16) 125.10 C2-C3-C11 121.46(17) 121.33 O2-C10-C11 130.62(17) 130.22 C11-C3-C4 108.52(15) 109.02 N1-C10-C11 105.18(14) 104.66 O3-C4-N1 124.68(17) 125.21 C3-C11-C10 108.45(15) 109.02 O3-C4-C3 130.57(18) 130.13 C12-C11-C3 120.89(16) 121.33 N1-C4-C3 104.75(15) 104.65 C12-C11-C10 130.65(17) 129.68 O1-C5-N2 120.37(15) 121.24 C11-C12-C13 117.3(2) 117.69 O1-C5-C6 123.32(15) 123.29 C1-C13-C12 122.07(19) 120.98 N2-C5-C6 116.29(14) 115.48 C6-C14-C15 120.88(18) 120.40 C7-C6-C5 118.43(15) 117.68 C9-C15-C14 117.99(19) 118.24 C14-C6-C5 123.27(15) 122.74 Table 4. Experimental and theoretical torsion angles of compound 4. Bond Torsion angles (°) Bond Torsion angles (°) XRD DFT (B3LYP/6-311G(d,p)) XRD DFT (B3LYP/6-311G(d,p)) F1-C9-C15-C14 179.94(18) -179.79 C4-N1-N2-C5 -87.5(2) 81.64 O1-C5-C6-C7 -10.9(3) -26.51 C4-N1-C10-O2 176.38(17) -178.54 O1-C5-C6-C14 166.49(17) 151.32 C4-N1-C10-C11 -3.42(18) 2.23 O2-C10-C11-C3 -177.48(19) 179.45 C4-C3-C11-C10 -0.46(18) 0.11 O2-C10-C11-C12 1.8(3) -0.68 C4-C3-C11-C12 -179.78(15) -179.77 N1-N2-C5-O1 -2.2(2) -3.55 C5-C6-C7-C8 178.07(16) 179.41 N1-N2-C5-C6 176.44(14) 177.15 C5-C6-C14-C15 -177.44(17) -178.98 N1-C10-C11-C3 2.30(18) -1.38 C6-C7-C8-C9 -0.8(3) -0.68 N1-C10-C11-C12 -178.46(17) 178.49 C6-C14-C15-C9 -0.2(3) 0.06 N2-N1-C4-O3 -4.8(3) 10.01 C7-C6-C14-C15 0.0(3) -1.20 N2-N1-C4-C3 175.53(14) -171.36 C7-C8-C9-F1 -179.46(17) -179.90 N2-N1-C10-O2 4.1(3) -9.29 C7-C8-C9-C15 0.6(3) -0.50 N2-N1-C10-C11 -175.68(14) 171.48 C8-C9-C15-C14 -0.1(3) 0.81 N2-C5-C6-C7 170.51(16) 152.78 C10-N1-N2-C5 84.1(2) -86.46 N2-C5-C6-C14 -12.1(2) -29.41 C10-N1-C4-O3 -177.14(18) 179.21 C1-C2-C3-C4 179.18(18) 179.93 C10-N1-C4-C3 3.15(18) -2.17 C1-C2-C3-C11 -0.3(3) 0.19 C10-C11-C12-C13 -178.58(17) 179.95 C2-C1-C13-C12 0.0(3) 0.04 C11-C3-C4-O3 178.79(19) 179.73 C2-C3-C4-O3 -0.7(3) -0.04 C11-C3-C4-N1 -1.53(18) 1.20 C2-C3-C4-N1 178.98(17) -178.56 C11-C12-C13-C1 -0.4(3) 0.17 C2-C3-C11-C10 179.09(16) 179.90 C13-C1-C2-C3 0.4(3) -0.22 C2-C3-C11-C12 -0.2(3) 0.02 C14-C6-C7-C8 0.5(3) 1.51 C3-C11-C12-C13 0.6(3) -0.20 Table 5. Hydrogen bond details of compound 4 *. Donor–Hydrogen···Acceptor D···H (Å) H···A (Å) D···A (Å) ∠ D–H···A (°) N2–H2A···O4 ii 0.86 1.96 2.75 153.6 C7–H7···O4 i 0.93 2.63 3.52 159.5 C14–H14···O4 i 0.93 2.59 3.38 143.2 O4–H4···O2 iii 0.93 1.90 2.81 167.0 O4–H3···O1 i 0.93 1.85 2.76 166.0 * Symmetry code: (i) x, -1+y, z (ii) x, y, z (iii) 1/2-x, 1/2+y, 1/2-z. The N-H···O and O-H···O hydrogen bonds linking molecules in the crystal form a three-dimensional framework structure. The linked benzene ring is twisted relative to the almost planar phthalimide ring system, forming a dihedral angle of 76.70(7)°. The phthalimide ring is largely planar, with a maximum deviation of 0.0479 Å for N1. In the carboxy group of the phthalimide, the carbon-oxygen distances are different in bond lengths (C10-O2 = 1.206(2) and C4-O3 = 1.190(3) Å). Intermolecular hydrogen bonding between molecules of N2- H2A···O4, O4-H4···O2 and O4-H3···O1 substantially strengthens these bonds. 3.3. Theoretical calculations DFT calculations were carried out for compound 4 at the B3LYP/6-311G(d,p) level of theory, and Figure 3 shows the optimized structure. Since the theoretical calculations are done for an isolated molecule in a gaseous phase and the experi- mental results are for a molecule in a solid state, a comparison of the theoretical values with the experimental ones shows that most of the optimized bond lengths are slightly larger than the experimental values (Table 2). The geometrical parameters obtained for compound 4 are given in Tables 2-4. Hirshfeld surface analysis was obtained utilizing the CIF file from single-crystal XRD analysis to quantify and depict multiple intermolecular contacts, and they were used to explore inter- molecular interactions and their quantitative contributions [29]. The region on the surface where atoms make intermole- cular interactions that are closer together than the sum of their Van der Waals radii is depicted by the color red. It is notable that the Hirshfeld surface depicts the H···H bond between H2A and H4 as a red spot, indicating that this is a major short- range H···H contact. Positive electrostatic potentials are corresponding to blue zones. Neutral potentials are indicated by the white regions. The contact distances dnorm contain both di (distance from the surface to the nearest atom inside the surface) and de (distance from the surface to the nearest atom outside the surface) shown in Figure 4. Elancheran et al. / European Journal of Chemistry 14 (1) (2023) 1-8 5 2023 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.14.1.1-8.2335 Table 6. Quantum chemical parameters and their values, as estimated by B3LYP/6-311G(d,p), include HOMO-LUMO energies of compound 4. Property * Values EHOMO -7.4173 eV ELUMO -2.8425 eV ∆ELUMO-HOMO 4.5748 eV Global hardness (η) 2.2874 eV Softness (ξ) 0.2186 eV Chemical potential (µ) 5.1299 eV Electrophilicity (ᴪ) 5.5752 eV Electronegativity (χ) -2.2874 eV Dipole moment (D) 4.1070 Debye * η =1/2[ELUMO-EHOMO], ξ =1/2η, µ = - [1/2(ELUMO + EHOMO)], ᴪ = µ2/2η, χ = - µ. Figure 3. Optimized molecular structure for compound 4. (a) (b) (c) Figure 4. (a) dnorm, (b) Shape-index, and (c) Curvedness mapped on the Hirshfeld surface of compound 4. The shape index surface in the structure of a molecule describes the surface and density of electrons surrounding a chemical interaction. The presence of C–H···Cg and cycle stacking (Cg–Cg) interactions are indicated by red and blue triangles, respectively. The Hirshfeld surface of compound 4 was depicted in three dimensions in Figure 4. On the curved- ness surface, the large flat region with a blue edge represents the interactions between the cycle stacking of the molecules shown in Figure 4. The fingerprint plot of compound 4 confir- med the presence of different intermolecular interactions with O···H/H···O (28.1%), H···H (26.8%), C···H/H···C (25.4%), H···F/F···H (12.3%), C···C (8.9%), C···O/O···C (4.7%), O···F/F···O (1.6%), N···H/H···N (1.0%). The yellowish bin on the fingerprint plots also pointed to the presence of a weak π-π stacking in the crystal structure shown in Figure 5. The most reactive site in π-electron systems is predicted using the frontier electron density, which is also used to explain a variety of reactions in the conjugated system [30]. Higher kinetic stability and lower chemical reactivity are always correlated with higher HOMO-LUMO gaps. To remove electrons from the low-lying HOMO, it is energetically unfavorable to add an electron to the high-lying LUMO. The HOMO-LUMO energy gap (4.5748 eV) is showing good stability of the molecule shown in Figure 6. The stability, chemical activity, softness, hardness, chemical potential, electronegativity, and electro- philicity index of a molecule are all reflected in its energy gap (Egap), according to Koopman’s Theorem. Table 6 shows all global reactivity values for the title compound. These parameters demonstrate that the molecule is stable when the chemical potential is negative and less reactive and more stable when the chemical hardness is high. The substance’s high electrophilicity index value makes it suitable for biological action. Dipole moment arises due to the difference in electronegative of the bonded atoms. The large magnitude of the dipole moment suggests that compound 4 may be attractive for further interactions with other systems. This typically happens when one atom has a larger electronegative value than the other atom, which allows the higher electronegative atom to pull the electron cloud more strongly. In order to perform as the best electron donor, compound 4 (EHOMO = -7.4173 eV) has a higher HOMO energy. In contrast, compound 4 (ELUMO = -2.8425 eV) has a lower LUMO energy. Attributed to the importance of these two qualities, the electronegativity (χ), the electronic chemical potential (μ), and the chemical hardness (η) are so significant. In addition, it is observed that compound 4 has a dipole moment of 4.1070 Debye. 6 Elancheran et al. / European Journal of Chemistry 14 (1) (2023) 1-8 2023 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.14.1.1-8.2335 Figure 5. Fingerprint plots of compound 4. Figure 6. HOMO-LUMO diagram of compound 4. 4. Conclusions A novel compound 4 was synthesized and thoroughly characterized using FT-IR, NMR, and HR-MS, and all of the obta- ined characterization data are consistent with the postulated structure. Compound 4 formed in a monoclinic system with the space group P21/n, and single crystal X-ray diffraction experi- ments verified its three-dimensional structure. By using DFT calculations, the obtained experimental bond angles, bond lengths, and torsion angles are in good agreement with the theoretical values. Furthermore, DFT/B3LYP/6-311G(d,p) cal- culation was used to obtain some molecular properties of compound 4. Investigating the stability, intramolecular charge transfers, donor-acceptor interactions, and strength of hydro- gen bonds in the synthesized molecule is supported by DFT, Hirshfeld surface analysis, and fingerprint plots. In this study, it is demonstrated that fingerprint plots are a useful tool for aiding the identification and measurement of intermolecular interactions. These findings encourage further studies on in silico molecular docking and anticancer activities. Elancheran et al. / European Journal of Chemistry 14 (1) (2023) 1-8 7 2023 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.14.1.1-8.2335 Acknowledgements Dr. Ramakrishnan Elancheran thanks DST-PURSE Phase II for the financial support. Prof. Senthamaraikannan Kabilan thanks The University Grants Commission, New Delhi, for the UGC BSR Faculty Fellowship. Supporting information CCDC-2201423 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via https://www.ccdc.cam. ac.uk/structures/, or by e-mailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223-336033. Disclosure statement Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: All ethical guidelines have been adhered. Sample availability: Sample of the title compound is available from the author. CRediT authorship contribution statement Conceptualization: Ramakrishnan Elancheran; Methodology: Ramakrishnan Elancheran; Software: Ramakrishnan Elancheran; Validation: Balakrishnan Karthikeyan; Formal Analysis: Ramakrishnan Elancheran; Investigation: Ramakrishnan Elancheran, Balakrishnan Karthikeyan; Resources: Senthamaraikannan Kabilan; Data Curation: Ramakrishnan Elancheran; Writing - Original Draft: Ramakrishnan Elancheran; Writing - Review and Editing: Balakrishnan Karthikeyan, S. Srinivasan; Visualization: S. Srinivasan; Funding acquisition: Senthamaraikannan Kabilan; Supervision: Balakrishnan Karthikeyan, Kuppusamy Krishnasamy, Senthamaraikannan Kabilan; Project Administration: Kuppusamy Krishnasamy, Senthamaraikannan Kabilan. ORCID and Email Ramakrishnan Elancheran srielancheran@gmail.com https://orcid.org/0000-0002-2819-5319 Balakrishnan Karthikeyan bkarthi_au@yahoo.com https://orcid.org/0000-0002-7545-1370 Subramanian Srinivasan drssvasan74@rediffmail.com https://orcid.org/0000-0003-0848-5236 Kuppusamy Krishnasamy krishnasamybala56@gmail.com https://orcid.org/0000-0001-5062-6982 Senthamaraikannan Kabilan profdrskabilanau@gmail.com https://orcid.org/0000-0002-8060-7886 References [1]. Halim, P. A.; Georgey, H. H.; George, M. Y.; El Kerdawy, A. M.; Said, M. F. Design and synthesis of novel 4-fluorobenzamide-based derivatives as promising anti-inflammatory and analgesic agents with an enhanced gastric tolerability and COX-inhibitory activity. Bioorg. Chem. 2021, 115, 105253. [2]. Aliabadi, A.; Mohammadi-Frarni, A.; Azizi, M.; Ahmadi, F. Design, synthesis and cytotoxicity evaluation of N-(5-benzylthio)-4H-1,2,4- triazol-3-YL)-4-fluorobenzamide derivatives as potential anticancer agents. Pharm. Chem. 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Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry). http://www.eurjchem.com/index.php/eurjchem/pages/view/terms http://creativecommons.org/licenses/by-nc/4.0 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms 1. Introduction 2. Experimental 2.1. General 2.2. Synthesis 2.3. X-ray structure determination 2.4. Computational methodology 3. Results and discussion 3.1. Chemistry 3.2. Crystal structure analysis 3.3. Theoretical calculations 4. Conclusions Acknowledgements Supporting information Disclosure statement CRediT authorship contribution statement ORCID and Email References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField15: PrintField16: PrintField17: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: PrintField25: PrintField26: PrintField27: