Crystal structure and Hirshfeld surface analysis of 3,4-dihydro-2-(2,4-dioxo-6-methylpyran-3-ylidene)-4-(4-pyridin-4-yl)-1,5-benzodiazepine

In the title compound, the pendant dihydropyran ring is rotationally disordered in a 90.899 (3):0.101 (3) ratio with the orientation of each component largely determined by intramolecular N—H⋯O hydrogen bonds. In the crystal, inversion-related molecules form dimers through intermolecular N—H⋯O hydrogen bonds with the dimers associated along the b-axis direction by slipped π-stacking interactions between the pyridyl and dihydropyran rings.


Chemical context
Diversely substituted 1,5-benzodiazepines and their derivatives embedded with a variety of functional groups are important biological agents and a significant amount of research activity has been directed towards this class of compounds. In fact, many 1,5-benzodiazepines are best known to possess biologically diverse activities such as anti-inflammatory, hypnotic, anti-HIV-1, anticonvulsant and antimicrobial (Roma et al., 1991;Kalkhambkar et al., 2008;Kudo, 1982;De Sarro et al., 1996;Kumar & Joshi, 2007). Various methods have been worked out for their synthesis (Dardouri et al., 2011;Chkirate et al., 2018;Sebhaoui et al., 2017). Benzodiazepine derivatives also find commercial use as dyes for acrylic fibers. The search for new heterocyclic systems including the 1,5-benzodiazepine moiety for their biological activities is therefore of much current importance (Tjiou et al., 2005;Keita et al., 2003;Jabli et al., 2009). In this context, we report herein the synthesis, the molecular and crystal structures along with the Hirshfeld surface analysis of the title compound.

Figure 2
Packing viewed along the a-axis direction. The intermolecular N-H Diazp Á Á ÁO Dhydp (Diazp = diazepine and Dhydp = dihydropyran) hydrogen bonds and slippedstacking interactions are shown, respectively, by blue and green dashed lines.
In the HS plotted over d norm (Fig. 3), the white area indicates contacts with distances equal to the sum of van der Waals radii, and the red and blue areas indicate distances shorter (in close contact) or longer (distinct contact), respectively, than the van der Waals radii (Venkatesan et al., 2016). The brightred spots appearing near O2 and hydrogen atoms H1 and H2A indicate their roles as the respective donors and/or acceptors in the dominant N-HÁ Á ÁO hydrogen bonds. The shape-index of the HS is a tool for visualizing thestacking by the presence of adjacent red and blue triangles; if there are no adjacent red and/or blue triangles, then there are nointeractions. Fig. 4 clearly suggest that there areinteractions in (I). The overall two-dimensional fingerprint plot, View of the three-dimensional Hirshfeld surface of the title compound plotted over d norm in the range À0.2111 to 1.1395 a.u.

Figure 4
Hirshfeld surface of the title compound plotted over shape-index.

Figure 5
The full two-dimensional fingerprint plots for the title compound  (Table 2). In the absence of C-HÁ Á Á interactions in the crystal, the pair of characteristic wings in the fingerprint plot delineated into HÁ Á ÁC/CÁ Á ÁH contacts (17.7% contribution to the HS) have a symmetrical distribution of points, Fig. 5(c), with the tips at d e + d i $2.82 Å . The two pairs of thin and thick spikes with the tips at d e + d i = 2.67 and 2.40 Å , respectively, in Fig. 5(d) are due to the N-HÁ Á ÁO hydrogen bonds (Table 1), as well as the short interatomic HÁ Á ÁO/OÁ Á ÁH contacts ( Table 2) The Hirshfeld surface analysis confirms the importance of H-atom contacts in establishing the packing. The large number of HÁ Á ÁH, HÁ Á ÁC/CÁ Á ÁH, HÁ Á ÁO/OÁ Á ÁH and HÁ Á ÁN/NÁ Á ÁH interactions suggest that van der Waals interactions and hydrogen bonding play the major roles in the crystal packing (Hathwar et al., 2015).

Synthesis and crystallization
To a suspension of 3-[1-(2-aminophenylimino)ethyl]-4-hydroxy-6-methylpyran-2-one (4 mmol) in ethanol (40 ml) were added 1.5 equivalents of 2-pyridinecarboxaldehyde and three drops of trifluoroacetic acid (TFA). The mixture was refluxed for 4 h. Cooling to room temperature induced the precipitation of a yellow solid, which was filtered off and washed with 20 ml of cold ethanol. Cooling to room temperature induced the precipitation of a yellow solid, which was filtered and washed with 20 ml of cold ethanol. Crystals suitable for X-ray  analysis were obrained by recrystallization of the product from ethanol solution.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. The pendant dihydropyran ring is rotationally disordered in a 90.899 (3):0.101 (3) ratio. As a result of this disorder, the hydrogen atoms on C17 and C20 and their disordered counterparts were placed in calculated positions and included as riding contributions. The alternate orientation of this ring was treated as a rigid group having the same geometry as the major component. The remaining H atoms were located in a difference-Fourier map and were freely refined.  SHELXTL (Sheldrick, 2008).

Special details
Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5 deg. in omega, colllected at phi = 0.00, 90.00 and 180.00 deg. and 2 sets of 800 frames, each of width 0.45 deg in phi, collected at omega = -30.00 and 210.00 deg. 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. Because of the slight disorder of the dihydropyranone ring, the hydrogen atoms on C17 and C20 and their disordered counterparts were placed in calculated positions and included as riding contributions. The alternate orientation of this ring was treated as a rigid group having the same geometry as the major component.