Crystal structure, Hirshfeld surface analysis and interaction energy calculation of 4-(furan-2-yl)-2-(6-methyl-2,4-dioxopyran-3-ylidene)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

The pyran ring is modestly non-planar while the tetrahydrodiazepine ring adopts a boat conformation. In the crystal, N—H⋯O hydrogen bonds and slipped π–π stacking interactions build a three-dimensional network structure.

The present study continues the investigation of 1,5benzodiazepine derivatives recently published by our team (El Ghayati et al., 2019Essaghouani et al., 2016Essaghouani et al., , 2017. In this context, we report herein the synthesis, the molecular and crystal structures along with the Hirshfeld surface analysis and the intermolecular interaction energies of the title compound, (I). ISSN 2056-9890

Figure 2
Portions of two chains viewed along the c axis direction with N-HÁ Á ÁO hydrogen bonds and slippedstacking interactions depicted, respectively, by violet and orange dashed lines.

Figure 3
Packing viewed along the a-axis direction with intermolecular interactions depicted as in Fig. 2.

Figure 1
The molecule of (I) with the atom-numbering scheme and displacement ellipsoids drawn at the 50% probability level. The intramolecular hydrogen bond is depicted by a dashed line.

Hirshfeld surface analysis
In order to visualize the intermolecular interactions in the crystal of (I), a Hirshfeld surface (HS) analysis (Hirshfeld, 1977) was carried out using Crystal Explorer 17.5 (Turner et al., 2017). In the HS plotted over d norm (Fig. 4a), the white surface indicates contacts with distances equal to the sum of van der Waals radii, and the red and blue colours indicate distances shorter or longer than the van der Waals radii, respectively (Venkatesan et al., 2016). The bright-red spots appearing near O3 and hydrogen atom H2A indicate their roles as the respective donor and/or acceptor atoms in hydrogen bonding. They also appear as blue and red regions corresponding to positive and negative potentials on the HS mapped over electrostatic potential (Spackman et al., 2008;Jayatilaka et al., 2005) as shown in Fig. 4b. The blue regions indicate the positive electrostatic potential (hydrogen-bond donors), while the red regions indicate the negative electrostatic potential (hydrogen-bond acceptors). The shape-index of the HS is a tool to visualize thestacking by the presence of adjacent red and blue triangles.  Fig. 5b-h, respectively, together with their relative contributions to the Hirshfeld surface. The most important interaction is HÁ Á ÁH (Table 2) contributing 46.8% to the overall crystal packing, which is reflected in Fig. 5b as widely scattered points of high density due to the large hydrogen content of the molecule with the tip at d e = d i = 1.07 Å . The pair of scattered points of spikes in the fingerprint plot delineated into HÁ Á ÁO/OÁ Á ÁH contacts (23.5% contribution to the HS, Fig. 5c; Table 2) have the tips at d e + d i = 2.09 Å . In the absence of C-HÁ Á Á interactions, the pair of characteristic wings in the fingerprint plot delineated into HÁ Á ÁC/CÁ Á ÁH contacts (Fig. 5d,  (a) View of the three-dimensional Hirshfeld surface of the title compound, plotted over d norm in the range of À0.3842 to 1.4934 a.u., (b) view of the three-dimensional Hirshfeld surface of the title compound plotted over 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 and (c) Hirshfeld surface of the title compound plotted over shape-index.  Table 2 Selected interatomic distances (Å ).
The Hirshfeld surface analysis confirms the importance of H-atom contacts in establishing the packing. The large number of HÁ Á ÁH, HÁ Á ÁO/OÁ Á ÁH, and HÁ Á ÁC/CÁ Á ÁH interactions suggest that van der Waals interactions play the major role in the crystal packing (Hathwar et al., 2015).

Interaction energy calculations
The intermolecular interaction energies were calculated using the CE-B3LYP/6-31G(d,p) energy model available in Crystal Explorer 17.5 (Turner et al., 2017), where a cluster of molecules is generated by applying crystallographic symmetry operations with respect to a selected central molecule within the default radius of 3.8 Å (Turner et al., 2014). The total intermolecular energy (E tot ) is the sum of electrostatic (E ele ), polarization (E pol ), dispersion (E dis ) and exchange-repulsion (E rep ) energies (Turner et al., 2015) with scale factors of 1.057, 0.740, 0.871 and 0.618, respectively (Mackenzie et al., 2017). The hydrogen bonding interaction energy for the N2-H2AÁ Á ÁO3 hydrogen bond was calculated (in kJ mol À1 ) as À32.6 (E ele ), À7.4 (E pol ), À60.8 (E dis ), 57.3 (E rep ) and À57.5 (E tot ).  (Fig. 7). All have the tetrahydrodiazepine ring adopting a boat conformation with puckering amplitudes in the range 0.702 (2) Å (for A) to 0.957 (2) Å (for C, R = thiophene). The dihedral angles between the mean planes of the benzo rings and those of the ring-containing substituents on the seven-membered ring vary considerably, likely due to packing considerations as the steric bulk of these groups differ markedly.

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 furan-2-carboxaldehyde and four drops of trifluoroacetic acid (TFA). The mixture was refluxed for 3 h. Cooling to room temperature induced the precipitation of a yellow solid, which was filtered off, and then washed with 20 ml of cold ethanol. Crystals suitable for X-ray analysis were obtained by recrystallization of the bulk from ethanol solution to afford colourless crystals (yield: 75%).

Refinement
Crystal, data collection and refinement details are presented in Table 3. Inspection of the data with CELL_NOW (Sheldrick, 2009) revealed that the crystal under investigation was twinned by a 180 rotation about the a* axis with a subse-  Diagrams of compounds structurally related to (I).
quently refined 78:22 ratio of the two twin components. The full two-component reflection file (HKLF-5 format) was used for the final refinement. Hydrogen atoms attached to carbon were included as riding contributions in idealized positions (C-H = 0.95-0.99 Å ) with U iso (H) = 1.2-1.5U eq (C). Those attached to nitrogen were restrained to a target bond length of 0.91 Å using the DFIX instruction in SHELXL. The displacement ellipsoids of the O1/C10-C14 ring suggest a possible slight disorder in this group, but it does not appear large enough to model with alternate locations of the atoms. Acta Cryst. (2021). E77, 834-838 research communications  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: publCIF (Westrip, 2010).

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 20 sec/frame. Analysis of 2110 reflections having I/σ(I) > 15 and chosen from the full data set with CELL_NOW (Sheldrick, 2008) showed the crystal to belong to the monoclinic system and to be twinned by a 180° rotation about the a axis. The raw data were processed using the multi-component version of SAINT under control of the two-component orientation file generated by CELL_NOW. 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 attached to carbon were placed in calculated positions (C-H = 0.95 -0.99 Å) and were included as riding contributions with isotropic displacement parameters 1.2 -1.5 times those of the attached atoms. Those attached to nitrogen were placed in locations derived from a difference map and refined with a DFIX 0.91 0.01 instruction. Refined as a 2-component twin.