Crystal structure, Hirshfeld surface analysis and interaction energy and DFT studies of (S)-10-propargylpyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione

The title compound consists of pyrrole and benzodiazepine units linked to a propargyl moiety, where the pyrrole and diazepine rings adopt half-chair and boat conformations, respectively. In the crystal, weak C—HBnz⋯ODiazp and C—HProprg⋯ODiazp (Bnz = benzene, Diazp = diazepine and Proprg = propargyl) hydrogen bonds link the molecules into two-dimensional networks parallel to the bc plane, enclosing (28) ring motifs.

The title compound, C 15 H 14 N 2 O 2 , consists of pyrrole and benzodiazepine units linked to a propargyl moiety, where the pyrrole and diazepine rings adopt halfchair and boat conformations, respectively. The absolute configuration was assigned on the the basis of l-proline, which was used in the synthesis of benzodiazepine. In the crystal, weak C-H Bnz Á Á ÁO Diazp and C-H Proprg Á Á ÁO Diazp (Bnz = benzene, Diazp = diazepine and Proprg = propargyl) hydrogen bonds link the molecules into two-dimensional networks parallel to the bc plane, enclosing R 4 4 (28) ring motifs, with the networks forming oblique stacks along the a-axis direction. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from HÁ Á ÁH (49.8%), HÁ Á ÁC/CÁ Á ÁH (25.7%) and HÁ Á ÁO/OÁ Á ÁH (20.1%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. Computational chemistry indicates that in the crystal, C-HÁ Á ÁO hydrogen-bond energies are 38.8 (for C-H Bnz Á Á ÁO Diazp ) and 27.1 (for C-H Proprg Á Á ÁO Diazp ) kJ mol À1 . Density functional theory (DFT) optimized structures at the B3LYP/6-311 G(d,p) level are compared with the experimentally determined molecular structure in the solid state. The HOMO-LUMO behaviour was elucidated to determine the energy gap.

Chemical context
Over the past few decades, compounds bearing heterocyclic nuclei have received much attention of chemists and biologists because of their importance in the development of chemotherapeutic agents and a wide variety of drugs (Cargill et al., 1974;Micale et al., 2004;Hadac et al., 2006;Ourahou et al., 2011). 1,4-Benzodiazepines and their derivatives have attracted the attention of chemists since the early 1960s, mainly because of the broad spectrum of biological properties exhibited by this class of compounds, in particular their psychopharmacological properties (Thurston & Langley, 1986;Kamal et al., 2007;Antonow et al., 2007;Archer & Sternbach, 1968;Mohiuddin et al., 1986, Bose et al., 1992Gregson et al., 2004). The vast commercial success of these medicinal agents has resulted in their chemistry being a major focus of research in the field of medicinal chemistry and many such ring systems having been described (Benzeid et al., 2009a,b;Randles & Storr, 1984;Sugasawa et al., 1985;Cipolla et al., 2009). Pyrrolo[2,1-c] [1,4]benzodiazepines are a group of potent chemicals produced by Streptomyces species. For their anticancer activity, see: Bose et al. (1992); Cargill et al. (1974); Gregson et al. (2004).
In a continuation of our research work on the advancement of benzodiazepine derivatives, we have developed a new synthethis for 10-propargylpyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione ( Fig. 1) in good yield from pyrrolo[2,1-c][1,4]benzodiazepine with propargylbromide in the presence of tetra-n-butylammonium bromide (TBAB) as catalyst and potassium carbonate as base (Makosza & Jonczyk, 1976). The synthesized compound was characterized by single-crystal X-ray diffraction as well as Hirshfeld surface analysis. The results of the calculations by density functional theory (DFT), carried out at the B3LYP/6-311G (d,p) level, are compared with the experimentally determined molecular structure in the solid state.

Hirshfeld surface analysis
In order to visualize the intermolecular interactions in the crystal of the title compound, a Hirshfeld surface (HS) analysis (Hirshfeld, 1977;Spackman & Jayatilaka, 2009) was carried out using Crystal Explorer 17.5 (Turner et al., 2017). In the HS plotted over d norm (Fig. 3), 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 (in close contact) or longer (distinct contact) than the van der Waals radii, respectively (Venkatesan et al., 2016). The molecular structure of the title compound with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Table 1 Hydrogen-bond geometry (Å , ). Symmetry codes: (vii) x; y; z þ 1; (viii) Àx þ 1; y À 1 2 ; Àz þ 1.

Figure 2
A partial packing diagram viewed along the a-axis direction with weak intermolecular C-H Bnz Á Á ÁO Diazp and C-H Proprg Á Á ÁO Diazp (Bnz = benzene, Diazp = diazepine and Proprg = propargyl) hydrogen bonds (dashed lines). H atoms not included in hydrogen bonding have been omitted for clarity. red spots appearing near O1, O2 and hydrogen atom H13A indicate their roles as the respective donors and acceptors; 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) shown in Fig View of the three-dimensional Hirshfeld surface of the title compound plotted over d norm in the range À0.1285 to 1.4451 a.u.

Figure 4
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. Hydrogen-bond donors and acceptors are shown as blue and red regions around the atoms, corresponding to positive and negative potentials, respectively.

Figure 5
Hirshfeld surface of the title compound plotted over shape-index. Table 2 Selected interatomic distances (Å ).
(1.8%) are reflected in Fig. 6f as thick wings with the tips at d e + d i = 3.04 Å . Selected contacts are listed in Table 2. The Hirshfeld surface representations with the function d norm plotted onto the surface are shown for the HÁ Á ÁH, HÁ Á ÁC/CÁ Á ÁH and HÁ Á ÁO/OÁ Á ÁH interactions in Fig. 7a-c, respectively.
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 and HÁ Á ÁO/OÁ Á ÁH interactions suggest that van der Waals interactions and hydrogen bonding play the major roles in the crystal packing (Hathwar et al., 2015).

DFT calculations
The optimized structure of the title compound in the gas phase was generated theoretically via density functional theory (DFT) using standard B3LYP functional and 6-311 G(d,p) basis-set calculations (Becke, 1993) as implemented in GAUSSIAN 09 (Frisch et al., 2009). The theoretical and experimental results were in good agreement (Table 3)    highest-occupied molecular orbital (HOMO), acting as an electron donor, and the lowest-unoccupied molecular orbital (LUMO), acting as an electron acceptor, are very important parameters for quantum chemistry. When the energy gap is small, the molecule is highly polarizable and has high chemical reactivity. The DFT calculations provide some important information on the reactivity and site selectivity of the molecular framework. E HOMO and E LUMO clarify the inevitable charge-exchange collaboration inside the studied material, and are given in Table 4 along with the electronegativity (), hardness (), potential (), electrophilicity (!) and softness (). The significance of and is to evaluate both the reactivity and stability. The electron transition from the HOMO to the LUMO energy level is shown in Fig. 8

Synthesis and crystallization
The synthesis of pyrrolobenzodiazepine is a simple condensation of isatoic anhydride on l-proline.

Figure 8
The energy band gap of the title compound. Computer programs: APEX3 and SAINT (Bruker, 2013), SHELXT (Sheldrick, 2015a), SHELXL (Sheldrick, 2015b) and OLEX2 (Dolomanov et al., 2009). catalytic amount of tetra-n-butyl ammonium bromide were stirred in N,N-dimethylformamide (20 ml) for 72 h. The solid material was removed by filtration and the solvent evaporated under vacuum. The residue was separated by chromatography on silica gel with an n-hexane-ethyl acetate (1:9) solvent system. The title compound was obtained as colourless crystals in 70% yield upon evaporation of the solvent.

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.