Synthesis, X-ray crystal structure, Hirshfeld surface analysis and DFT studies of (E)-N′-(2-bromobenzylidene)-4-methylbenzohydrazide

The title molecule displays a trans configuration with respect to the C=N double bond. The dihedral angle between the bromo- and the methyl-substituted benzene rings is 16.1 (3)°. In the crystal, molecules are connected by N—H⋯O and weak C—H⋯O hydrogen bonds, forming (6) ring motifs and generating chains along the a–axis direction.

The title molecule, C 15 H 13 BrN 2 O, displays a trans configuration with respect to the C N double bond. The dihedral angle between the bromo-and methylsubstituted benzene rings is 16.1 (3) . In the crystal, molecules are connected by N-HÁ Á ÁO and weak C-HÁ Á ÁO hydrogen bonds, forming R 2 1 (6) ring motifs and generating chains along the a-axis direction. The optimized structure generated theoretically via density functional theory (DFT) using standard B3LYP functional and 6-311 G(d,p) basis-set calculations renders good support to the experimental data. The HOMO-LUMO behaviour was elucidated to determine the energy gap. The intermolecular interactions were quantified and analysed using Hirshfeld surface analysis.

Chemical_context
Hydrazones are a class of organic compounds that possess an R1R2C NNH 2 structural motif. They are related to ketones and aldehydes in which oxygen has been replaced with an NNH 2 group (Rollas & Kü çü kgü zel, 2007). Azomethines, -NHN CH-, constitute an important class of compounds for new drug development. The reaction of a hydrazine or hydrazide with aldehydes and ketones yields hydrazones. Hydrazones are important in drug design as they act as ligands for metal complexes, organocatalysis and the synthesis of organic compounds. The C N bond of the hydrazone and the terminal nitrogen atom containing a lone pair of electron is responsible for the physical and chemical properties. The C atom in the hydrazone unit has both electrophilic and nucleophilic character and both the N atoms are nucleophilic, although the amino-type nitrogen is more reactive. As a result of these properties, hydrazones are widely used in organic synthesis. Owing to their ease of preparation and diverse pharmacological potential, much work on hydrazones has been carried out by medicinal chemists to develop agents with better activity and low toxicity profiles. Hydrazones are known to possess diverse biological activities such as antimicrobial, anti-inflammatory, anticancer and antimalarial (Yousef et al., 2003;Trepanier et al., 1966) and have been evaluated for inhibition of PDE10A, a phosphodiesterase responsible for neurological and psychological disorders such as Parkinson's, schizophrenia and Huntington's disease (Gage et al., 2011). The anticonvulsant potential of some hydrazone derivatives having long duration and rapid onset of action have been reported (Kaushik et al., 2010), as has their anti-depressant activity (de Oliveira et al., 2011).
Schiff bases are used widely in the field of coordination chemistry and have interesting properties (Morshedi et al., 2009;Zhou et al., 2006;Khanmohammadi et al., 2009). These compounds are synthesized by condensation of carbonyl compounds with amines (van den Ancker et al., 2006;Hamaker et al., 2010). In addition, free Schiff base compounds are reported to possess antimicrobial (Aslantas et al., 2009) and non-linear optical (Karakaş et al., 2008) properties. Our previous work on (E)-4-bromo-N 0 -(2,4-dihydroxybenzylidene)benzohydrazide and (E)-4-toluic -N 0 -(2,4-dihydroxybenzylidene)benzohydrazide have been recently reported (Arunagiri et al., 2018a,b). This work has been a guide for the development of the new Schiff base title compound, which possesses electronic and non-linear properties. As part of our interest in the identification of bioactive compounds, we report herein on its crystal structure.

Structural commentary
The molecular structure of the title compound is shown in Fig. 1(a). The molecule adopts an (E) configuration across the C N bond, joining the hydrazide group and the benzene ring. In the crystal, the dihedral angle between the bromo-and methyl-substituted benzene rings is 16.1 (3) . The structure was optimized with the Gaussian09W software (Frisch et al., 2009) using the DFT-B3LYP/6-311G(d,p) method, providing information about the geometry of the molecule. The optimized structure is shown in Fig. 1(b). The geometrical parameters (Table 1) are mostly within normal ranges, the slight deviations of the theoretical values from those determined experimentally are due to the fact that the optimization is performed in isolated conditions, whereas the crystal environment and hydrogen-bonding interactions affect the results of the X-ray structure (Zainuri et al., 2017). The hydrazide unit (N1/N2/C1/C8-C10) is essentially planar, with a maximum deviation from the least-squares plane of 0.099 (4) Å for atom C10. The O1 C8 bond length [1.225 (6) and 1.219 Å for XRD and B3LYP, respectively] indicates single-bond character. The N1-N2 bond length [1.379 (5) Å for XRD and 1.364 Å for B3LYP] is in good agreement with other experimental values (Sivajeyanthi et al., 2017). The C-N bond lengths range from a typical single bond [C8-N1 = 1.351 (6) Å ] to a double bond [C9 N2 = 1.270 (6) Å (Sivajeyanthi et al., 2017;Arunagiri et al., 2018a,b).

Hirshfeld surface analysis
Hirshfeld surface analysis (McKinnon et al., 2007;Spackman & Jayatilaka, 2009) along with decomposed 2D fingerprint plots (Spackman & McKinnon, 2002;McKinnon et al., 2004McKinnon et al., , 2007 mapped over d norm , shape-index and curvedness were used to visualize and quantify the intermolecular interactions. The Hirshfeld surface (HS) and fingerprint plots were generated based on the d i and d e distances using Crystal Explorer3.1 (Wolff et al., 2012) where d i is the distance from the nearest atom inside the surface, while d e is the distance from the HS to the nearest atom outside the surface. In the d norm surfaces, large circular depressions (deep red) are the indicators of hydrogen-bonding contacts whereas other visible spots are due to HÁ Á ÁH contacts. The dominant HÁ Á ÁO interaction in the title compound is evident as a bright-red area in Fig. 3

Frontier molecular orbitals and Molecular electrostatic potential analysis
The highest-occupied molecular orbital (HOMO), which acts as an electron donor, and the lowest-unoccupied molecular orbital (LUMO), which acts as an electron acceptor, are very important parameters for quantum chemistry. If the energy gap is small, then the molecule is highly polarizable and has The three-dimensional d norm surface of the title compound. add contouring levels

Figure 4
Hirshfeld surfaces mapped over (a) shape-index and (b) curvedness for the title compound.

Figure 2
Part of the crystal structure with hydrogen bonds shown as dashed lines.

Figure 5
Two-dimensional fingerprint plots with the relative contributions of the various interactions.
high chemical reactivity. The energy levels were computed by the DFTB3LYP/6-311G(d,p) method (Becke et al., 1993) as implemented in GAUSSIAN09W (Frisch et al., 2009). The electron transition from the HOMO to the LUMO energy level is shown in Fig. 6. The molecular orbital of HOMO contain both and electron-density character, whereas the LUMO is mainly composed of -orbital density. The energy band gap (ÁE) of the molecule is about 4.42 eV. The Gauss-Sum2.2 program (O'Boyle et al., 2008) was used to calculate group contributions to the molecular orbitals (HOMO and LUMO) and prepare the density of states (DOS) spectrum shown in Fig. 7. The DOS spectrum was formed by convoluting the molecular orbital information with GAUS-SIAN curves of unit height. The green and red lines in the DOS spectrum indicate the HOMO and LUMO levels. The DOS spectrum supports the energy gap calculated by HOMO-LUMO analysis. A molecule with a large energy gap is described as hard while one having a small energy gap is known as a soft molecule. Hard molecules are not more polarizable than the soft ones because they require immense excitation energy (Karabacak & Yilan, 2012).
The molecular electrostatic potential is related to the electron density and molecular electrostatic potential (MESP) maps are very useful descriptors for understanding reactive sites for electrophilic and nucleophilic reactions as well as hydrogen-bonding interactions (Sebastian & Sundaraganesan, 2010;Luque et al., 2000). Different values of the electrostatic potential are represented by different colours: red represents regions of the most electronegative electrostatic potential, blue represents regions of the most positive electrostatic potential and green represents regions of zero potential. The potential increases in the following order: red < orange < yellow < green < blue. Herein, MEP was calculated at the DFT-B3LYP/6-311(d,p) level of theory that was used for optimization. The MESP map for the title molecule is shown in Fig. 8 with a colour range from À0.053 (red) to 0.053 a.u. (blue). The most electrostatically positive region (blue colour) is located in the molecular plane (N-bonded hydrogen atoms of toluic hydrazide), thus explaining N1-H1Á Á ÁO1 i hydrogen bond observed in the crystal structure. The map clearly shows that the electron-rich (red) region is spread around the carbonyl oxygen atom whereas the hydrogen atom attached to nitrogen is positively charged (blue). The molecular electrostatic potential map for the title compound.

Figure 6
The energy band gap of the compound.

Figure 7
The density of states (DOS) spectrum of the compound.

Synthesis and crystallization
The title compound was synthesized by the condensation of 4toluic hydrazide and 2-bromobenzaldehyde (Fig. 9). An ethanol solution (10ml) of 4-toluic hydrazide (0.25 mol) was mixed with ethanol solution of 2-bromobenzaldehyde (10 ml, 0.25 mol) and the reaction mixture was heated at 323 K for half an hour with constant stirring before being was filtered and kept for crystallization. After a period of one week, brown block-shaped crystals of the title compound were obtained.

X-ray crystallography and refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. The hydrogen atom on N1 (H1) was located in a difference-Fourier map and freely refined. Cbound hydrogen atoms were placed in calculated positions (C-H = 0.93-0.96 Å ) and refined as riding with U iso (H) =1.2U eq (C) or 1.5U eq (C-methyl).  Reaction scheme. Computer programs: APEX2, SAINT and XPREP (Bruker, 2004), SIR97 (Altomare et al., 1999), SHELXL014 (Sheldrick, 2015) and ORTEP-3 for Windows (Farrugia, 2012). Data collection: APEX2 (Bruker, 2004); cell refinement: APEX2 and SAINT (Bruker, 2004); data reduction: SAINT and XPREP (Bruker, 2004); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL014 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015). 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. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.  (2)