Crystal structure, DFT calculation, Hirshfeld surface analysis and energy framework study of 6-bromo-2-(4-bromophenyl)imidazo[1,2-a]pyridine

The molecular system displays a planar conformation between the phenyl and imidazo[1,2-a] pyridine rings. Weak C—H⋯π and π–π interactions as well as short contacts consolidate the three-dimensional network structure.


Chemical context
Five-membered heterocyclic compounds comprising a nitrogen atom and at least one other non-carbon atom (i.e. nitrogen, sulfur, or oxygen) as part of the ring are known as azoles. To date, numerous azoles have found a wide range of applications in various fields, including agriculture (Berger et al., 2017), and because of their biological activities (Pozharskii et al., 2011;Kumbar et al., 2018). Among the various classes of azoles, the imidazole moiety with two nitrogen atoms is extremely common in nature and forms the core of many biomolecules (Chopra & Sahu, 2019) and synthetic drugs (Pozharskii et al., 2011). Furthermore, pyridine and its derivatives are present in many important compounds, including pharmaceuticals, vitamins (Al-Ghorbani et al., 2016) and drugs, acting as antimicrobial, antiviral, antioxidants, antidiabetic, anti-malarial, anti-inflammatory or antiamoebic agents, as well as psychopharmacological antagonists (Altaf et al., 2015). Hence, the combination of pyridine and imidazole derivatives has been proven to result in highly active agents in ISSN 2056-9890 diverse biological fields that include anticancer (Kamal et al., 2014;Mantu et al., 2016), anti-HIV (Bode et al., 2011), antibacterial (Rival et al., 1992) and anti-inflammatory (Rupert et al., 2003) properties. In addition, such a combination showed significant activity against the human cytomegalo virus and the varicella-zoster virus (Gueiffier et al., 1998;Mavel et al., 2002).
In this context, we synthesized a new imidazo[1,2-a] pyridine derivative, C 13 H 8 Br 2 N 2 , and report herein its molecular and crystal structure, as well as the quantification of supramolecular interactions by Hirshfeld surface analysis. This study is supplemented by DFT calculations and a comparison of structural details with related compounds.

Figure 2
The crystal packing of the title compound in a view along [001], showing interactions in the sheets. H5Á Á ÁH5 short contacts are represented as blue dashed lines, C3-H3Á Á ÁCg3 interactions as red dashed lines (slippage 1.676 Å ) and Cg3Á Á ÁCg1 and Cg3Á Á ÁCg2 interactions as light-green dashed lines.

Figure 1
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level. The intramolecular C-HÁ Á ÁN hydrogen bond forming an S(5) ring motif is shown with dashed lines.

DFT study and FMOs
Density functional theory (DFT) calculations were carried out by using the B3LYP basis set (Becke, 1993) at the highest basis set level of 6-311 ++G(d,p) in the GAUSSIAN09 program (Frisch et al., 2009). The DFT-optimized structure of the title compound is generally found to be in good agreement with the experimental data for all bond lengths and angles. Frontier molecular orbitals (FMOs) are useful to specify the distribution of electronic densities and other quantum chemical parameters including hardness (), softness (), chemical potential (), electrophilicity ( ) and electronegativity () by foreseeing the highest occupied molecular orbitals (HOMO) and the lowest-unoccupied molecular orbitals (LUMO), as well as the energy gap (E g = E H -E L ) . The results of these calculations are compiled in Table 2, and orbital energy plots of (E H , E H-1 ) and (E L , E L+1 ) are depicted in Fig. 4. The HOMO (ground state) manifests the highest characterization for phenyl ring (C1-C6) that displays bifurcatedstacking interactions as well as C-HÁ Á Á interactions in the supramolecular network, as discussed in Section 3. Pronounced character of the electron density is located on the two Br atoms, with the higher amount located on Br1. The other FMOs orbitals, i.e. HOMO-1, LUMO and LUMO+1, exhibit a mix of and character on the rings with variations of the electron density distribution (Fig. 4). The HOMO-LUMO gap is 4.343 eV for the title compound.

Hirshfeld surface analysis
The nature of intermolecular interactions in the title compound has been computed by CrystalExplorer17.5 (Turner et al., 2017), using Hirshfeld surface analysis (Spackman & Jayatilaka, 2009) and two-dimensional fingerprint plots (McKinnon et al., 2007). The d norm plot was estimated via calculations of the external (d e ) and internal (d i ) distances to the nearest nucleus and built over the volume of 363.34 Å 3 and an area of 339.81 Å 2 , with scaled colour of À0.1544 (red) a.u. to 1.0479 (blue) a.u. (Fig. 5a). The plots of shape-index and curvedness were generated in the range of À4.0 to 4.0 a.u. and

Figure 4
Electron distribution and molecular orbital energies of HOMO-1, HOMO, LUMO and LUMO+1 of the title compound.

Figure 3
The three-dimensional supramolecular network of the title compound viewed approximately along [010].  À1.00 to 1.00 a.u., respectively, (Fig. 5b,c). The medium dark and side pale-red spots on the Hirshfeld surface (Fig. 5a) symbolize the H5Á Á ÁH5 and Br1Á Á ÁH12 short contacts, respectively. The two-dimensional fingerprint plot for all contacts is depicted in Fig. 6a. The HÁ Á ÁBr/BrÁ Á ÁH contacts make the largest contribution (26.1%) to the Hirshfeld surface (Fig. 6b). These contacts also make a significant contribution to the crystal packing as the distance between the atoms involved is slightly less than their van der Waals radii (d i + d e ' 3.01 Å ). The interatomic contacts of HÁ Á ÁH interactions generated 22.7% of the Hirshfeld surface (Fig. 6c) 3.6 Å , indicatingstacking interactions in the crystal packing. This type of stacking interaction appears as a flat region on the curvedness (Fig. 5c) and also on the shape-index as red and blue triangles on the rings (Fig. 5b), in particular on the phenyl ring (C1-C6). The contributions from other contacts have negligible effects on the packing.

Synthesis and crystallization
5-Bromopyridin-2-amine (1.211 g, 0.007 mol) and phenacyl bromide (0.007 mol) were refluxed for 14 h in 50 ml of absolute ethanol. The progress of the reaction was monitored by thin layer chromatography using Merck alumina backed silica gel 60 F254. After completion of the reaction, the resulting product was poured into crushed ice to obtain a fine grained solid product that was filtered off, separated and dried. The crude product was then recrystallized from hot ethanol with a yield of $70%. The melting point of 345 K was determined in an open capillary and is uncorrected. IR (KBr, cm À1 ): 3080 (Ar C-H stretch), 2918 (aliphatic C-H stretch, 4-bromophenyl moiety), 1587 (C N stretch), 1332 (C-N), 792 and 595 (C-Br

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4. Hydrogen atoms were placed in calculated positions (C-H = 0.93 Å ) and were included in the refinement in the riding-model approximation, with U iso (H) set to 1.2U eq (C). The reflection (002) was affected by the beam-stop and was removed from the refinement Data collection: APEX2 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: Mercury (Macrae et al., 2008) and PLATON (Spek, 2009); software used to prepare material for publication: publCIF (Westrip, 2010). Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.