A Hirshfeld Surface Analysis and Crystal Structure of 2 ’-[ 1-( 2-Fluoro-Phenyl )-1 H-tetrazol-5-Yl ]-4-Methoxy-Biphenyl-2-Carbaldehyde

The title compound, C21H15FN4O2 is synthesized and characterized by H NMR, LC-MS and finally confirmed by single crystal X-ray diffraction method. This molecule crystallizes in the monoclinic crystal system and space group P21/c, with crystal parameters a = 9.4386(5) Å, b = 20.8082(1) Å, c = 9.4338(6) Å, β = 99.566(2), Z = 4 and V = 1826.98(19) Å. The mean planes of fluro-phenyl moiety makes a dihedral angle of 21.51 (7) with biphenyl moiety. The molecules are connected by hydrogen bonds of the type C---H...O and C---H...F. In addition, crystal structure is stabilized with π ... π (exhibits intramolecular interaction) and C---O... π interactions. The intercontacts in the crystal structure are analyzed using Hirshfeld surfaces computational method.


Experimental
All reagents were purchased as reagent grade and used without further purification.The reaction was monitored and determination of product was accomplished by TLC technique.The melting point was determined on SE-LACO-650 hot stage apparatus.Elemental analysis (C, H, N) were determined with Vario-EL instrument. 1 H NMR spectra were recorded on a bruker DRX 300 MHz spectrometer using DMSO-d6 as solvent and TMS as internal standard.Chemical shifts are given in δ (ppm).coupling (Figure 1) of the compound 1-(2-Flurophenyl)-1H-tetrazole (1mmol), 1), with 2-formyl-4-methoxy phenyl boronic acid (1 mmol) in presence of sodium carbonate (15 mmol) and palladium catalyst in a mixture of dimethyl ether (DME) and water in the ratio 3:1.Then the mixture was degasified by bubbling with nitrogen for 15 minutes.After degasify PdCl 2 (PPh 3 ) 2 [dikis] (0.05 mmol) was added.The resultant mixture was heated at 80˚C under nitrogen atmosphere for 5 hours.After completion of reaction (monitored by TLC), the reaction mixture was concentrated under reduced pressure to remove DME.Then residue was dissolved with ethyl acetate (25 mL), washed with 0.1 N hydrochloric acid (2 * 25 mL), followed by brine solution (2 * 25 mL).Then, the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford crude 2'-[1-(2-Fluorophenyl)-1H-tetrazol-5-yl]-4-methoxy-biphenyl-2-carbaldehyde.2), which was purified by column chromatography over silica gel (60 -120 mesh) using Hexane: Ethyl acetate mixture in 8:2 ratios as eluent.The pure compound 2 was crystallized in ethyl acetate and hexane to obtain colorless single crystals.

Crystal Structure Determination
A good single crystal of the title compound with dimension 0.30 × 0.35 × 0.35 mm was chosen for X-ray diffraction study.Data collection and cell refinement were carried out using Bruker Kappa ApexII CCD diffractometer [21] with MoKα radiation.The absorption correction was applied using multi-scan technique for data collection.The lattice parameters were determined by the least-squares methods on the basis of all reflections with F 2 > 2σ (F 2 ).The structure was solved by the direct methods using SHELXS-97 [22,23].All the non-hydrogen atoms were revealed in the Fourier map itself.Full-matrix least squares refinement using SHELXL-97 [22,23] with isotropic temperature factors for all the atoms was done.Refinement of non-hydrogen atoms with anisotropic parameters was started at this stage.The hydrogen atoms were placed at chemically acceptable positions and were allowed to ride on their parent atoms.About 165 parameters were refined with 3213 unique reflections which saturated the residuals to R1 = 0.0375 and wR2 = 0.1071.The details of the crystal data and refinement are given in Table 1.Table 2 lists the hydrogen bonds.All the figures (ORTEP, packing and hydrogen bonding) were plotted using MERCURY [24].Hirshfeld surface analyses were carried out and finger print plots were plotted using CRYSTALEXPLORER [25].Electrostatic potentials were calculated using TONTO [26,27].

Hirshfeld Surface Analysis
The intermolecular interactions of the title compound are quantified using Hirshfeld surface analysis.This approach is a graphical tool for visualization and understanding of intermolecular interactions [25].Here, we estimate the intermolecular contacts, which are shown in    The electrostatic potential is mapped on Hirshfeld surface using STO-3G basis set at the Hartree-Fock theory over the range of ± 0.025 au (Figure 10).The positive electrostatic potential (blue region) over the surface indicates hydrogen donor potential, whereas the hydrogen bond acceptors are represented by negative electrostatic potential (red region) [27].The crystal geometries were         used as input to the TONTO [26] integrated with Crystal explorer [25].

Conclusion
The dihedral angle between fluro-phenyl moiety and biphenyl moiety is 21.51

Figure 1 .
Figure 1.Schematic diagram and synthesis pathway of the title compound.

Figure 2 . 1 H
Figure 2. 1 H NMR spectra of the title compound.

Figure 3 .
Figure 3. LC-MS spectra of the title compound.are highlighted by conventional mapping of d norm on molecular Hirshfeld surfaces are shown in Figure 8.The red spots over the surface indicate the intercontacts involved in the hydrogen bonds.Further, intercontacts were plotted with fingerprint plots (Figure.9).H...H intercontacts, (Figure 9(a)) shows large surfaces, whereas the O...H plot (Figure 9(d)) shows the presence of O...H contact with the two characteristic wings.The N...H contact plot is shown in Figure 9(b).The intercontacts F...H (Figure 9(e)) showing two narrow pointed wings provide evi-

Figure 4 .
Figure 4. Molecular structure of the title compound showing the atomic numbering system.Displacement ellipsoids are drawn at the 50% probability.

Figure 5 .
Figure 5. Packing diagram of the title molecule along b-axis.Dotted lines represents hydrogen bonds.

Figure 7 .
Figure 7. Hirshfeld surface: Percentage of various intermolecular contacts contributed to the Hirshfeld surface.

Figure 8 .
Figure 8. d norm mapped on Hirshfeld surface for visualizing the intercontacts of the title compound.Color scale in between −0.18 au (blue) to 1.4 au (red).Dotted lines (magenta) represent hydrogen bonds.

Figure 9 .
Figure 9. Fingerprint of the title compound, (a) H...H, (b) C...H, (c) C...H, (d) O...H and (e) F...H.The outline of the full fingerprint is shown in gray.d i is the closest internal distance from a given point on the Hirshfeld surface and de is the closest external contacts.

Figure 10 .
Figure 10.Electrostatic potential mapped on Hirshfeld surface (different orientation) with ± 0.25 au.Blue region corresponds to positive electrostatic potential and red region to negative electrostatic potential.
(7) 0 .The molecules are connected by C-H...O and C-H...F hydrogen bonds.In addition, the short contacts of the type ... and C---O... help in crystal stabilization.The Hirshfeld surface analysis with finger plots and electrostatic potential map reveals the percentage of intermolecular contacts and distribution of electrostatic potential of the title compound.