Crystal structure, Hirshfeld surface analysis and DFT study of N-(2-amino-5-methylphenyl)-2-(5-methyl-1H-pyrazol-3-yl)acetamide

The title molecule adopts an angular conformation. In the crystal, N—H⋯O and N—H⋯N hydrogen bonds together with C—H⋯π(ring) interactions form chains extending along the a-axis direction. Additional N—H⋯O hydrogen bonds link the chains into layers parallel to (100).


Chemical context
Nitrogen-based structures have attracted more attention in recent years because of their interesting properties in structural and inorganic chemistry (Lahmidi et al., 2018;Chkirate et al., 2020a;Taia et al., 2020;Al Ati et al., 2021). The pyrazolylacetamide family is important in medicinal chemistry because of the wide range of pharmacological applications (Deprez-Poulain et al., 2011) such as anti-inflammatory (Sunder et al., 2013), antimicrobial and anticancer (Jitender Dev et al., 2017) and as an anti-amoebic agent (Shukla et al., 2020). They also have antioxidant activity (Chkirate et al., 2019a) and have been biologically evaluated (Yan et al., 2021). Given the wide range of therapeutic applications for such compounds, and in a continuation of the work already carried out for the synthesis of compounds resulting from 1,5-benzodiazepine (Chkirate et al., 2001(Chkirate et al., , 2019b(Chkirate et al., , 2020bIdrissi et al., 2021) a similar approach gave the title compound, N-(2-amino-5-methylphenyl)-2-(5-methyl-1H-pyrazol-3-yl)acetamide, (I). Besides the synthesis, we also report the molecular and crystal structures along with a Hirshfeld surface analysis and a density functional theory computational calculation carried out at the B3LYP/6-311 G(d,p) level.

Figure 3
Packing arrangement viewed along the c-axis direction of the main isomer with intermolecular interactions shown as in Fig. 2.

Figure 1
Molecular structure of the title compound with the labelling scheme. The ellipsoids are drawn at the 50% probability level.

Figure 2
A portion of one chain projected onto (011)

Density functional theory calculations
The structure in the gas phase of the title compound was optimized by means of density functional theory. The density functional theory calculation was performed by the hybrid B3LYP method and the 6-311 G(d,p) basis-set, which is based on Becke's model (Becke, 1993) and considers a mixture of the exact (Hartree-Fock) and density functional theory exchange utilizing the B3 functional, together with the LYP correlation functional (Lee et al., 1988). After obtaining the converged geometry, the harmonic vibrational frequencies were calculated at the same theoretical level to confirm that the number of imaginary frequencies is zero for the stationary point. Both the geometry optimization and harmonic vibrational frequency analysis of the title compound were done with the Gaussian 09 program (Frisch et al., 2009). Theoretical and experimental results related to bond lengths and angles are in good agreement and are summarized in Table 2.
Calculated numerical values for the title compound including electronegativity (), hardness (), ionization potential (I), dipole moment (), electron affinity (A), electrophilicity (!) and softness () are collated in   View of the three-dimensional Hirshfeld surface of the title compound plotted over the electrostatic potential energy in the range À0.0500 to 0.0500 a.u. using the STO-3 G basis set at the Hartree-Fock level of theory.

Figure 5
Hirshfeld surface of the title compound plotted over shape-index.

Synthesis and crystallization
1.5 times those of the attached atoms. Residual density observed after the initial refinement converged was identified as an isomer of the primary molecule having the C7 methyl group attached to C3 instead of to C4 and with a refined occupancy of 5%. The final model was generated with a combination of rigid group and restrained refinement to make the minor component have a comparable geometry to that of the major component.   program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/1 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Special details
Experimental. The diffraction data were obtained from 9 sets of frames, each of width 0.5° in ω or φ, collected with scan parameters determined by the "strategy" routine in APEX3. The scan time was 15 sec/frame. 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. H-atoms were included as riding contributions in idealized positions with isotropic displacement parameters 1.2 -1.5 times those of the attached atoms. Residual density observed after the initial refinement converged was identified as an isomer of the primary molecule having the C7 methyl group attached to C3 instead of to C4 and with a refined occupancy of 5%. The final model was generated with a combination of rigid group and restrained refinement to make the minor component have a comparable geometry to that of the major component.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ. (