Crystal structure, Hirshfeld surface analysis and DFT calculations of 7-bromo-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one

The crystal structure of the title compound has been characterized by single-crystal X-ray diffraction and Hirshfeld surface analyses. The molecular structure and frontier orbitals were also investigated using DFT.

The molecular structure of the title compound, C 11 H 9 BrN 2 O, is almost planar. The benzene and pyrimidine rings are essentially coplanar, with r.m.s. deviations of 0.0130 Å , and the largest displacement is for the flap atom of the dihydropyrrole moiety [0.154 (7) Å ]. Hirshfeld surface analyses revealed that the crystal packing is dominated by HÁ Á ÁH, BrÁ Á ÁH/HÁ Á ÁBr and OÁ Á ÁH/HÁ Á ÁO interactions, and BrÁ Á ÁBr interactions in the crystal structure are also observed. Theoretical calculations using density functional theory (DFT) with the B3LYP functional basis set gave numerical parameters for the frontier molecular orbitals.

Chemical context
Quinazolines are of significant interest for their various biological properties (Rajput et al., 2012;Ramesh et al., 2012;Khan et al., 2014;Ajani et al., 2016). This class of compounds is considered as an attractive target for medicinal chemists, because quinazoline and its derivatives are the scaffold of several potent antitumor drugs, for example the well-known erlotinib and gefitinib (Sordella et al., 2004;Raymond et al., 2000). Besides these two drugs, the Food and Drug Administration (FDA) has approved some other quinazolines as effective anticancer drugs, viz. lapatinib and vandetanib. In general, the reported biological activities of quinazolines include antibacterial, anti-inflammatory, CNS depressant, anticonvulsant, antifungal, antimalarial, anticancer properties, which make them interesting for the pharmaceutical industry (Ajani et al., 2015).
In this context, synthetic analogues of the tricyclic quinazoline-9-one-7-bromo-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one have been synthesized, amongst them the title compound with a bromine atom in position 7. In comparison with a reported literature procedure (Shakhidoyatov, 1983), this compound is now obtained in higher yields (80-88%). For this purpose, condensation of 2-amino-5-brombenzoic acid with appropriate pyrrolidin-2-one was used whereas in the literature (Shakhidoyatov, 1983), 2-amino-5-brombenzoic acid was added to the corresponding lactam mixture with a condensing agent (POCl 3 ) at room temperature (293-298 K) and the reaction products separated by extraction after the reaction mixture was reduced to pH = 9-10 with NH 4 OH. As distinguished from the reported procedure, we carried out these reactions by cooling in an ice bath at a much lower temperature (273-275 K) and for a relatively longer period of time. The reaction products were finally separated by cold NH 4 OH at pH = 10-11. In general, the interactions of 7-bromo-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one with aldehydes are well-studied (Abdurazakov et al., 2007).
Here, we report the molecular and crystal structures as well as Hirshfeld surface analysis and the frontier molecular orbitals calculated by density functional theory (DFT) with the B3LYP functional basis set.

Figure 3
The packing of the title compound in a view approximately along [001], showing stacking between adjacent molecules in terms of Cg2Á Á ÁCg2 (blue dashed lines) and Cg2Á Á ÁCg3 (red dashed lines) interactions. Cg2 is the centroid (blue sphere) of the pyrimidine ring and Cg3 is the centroid (red sphere) of the benzene ring. H atoms are omitted for clarity.

Figure 1
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level.

Figure 4
Packing of the title compound along [100], with intermolecular C-HÁ Á ÁN contacts shown as light-blue dashed lines.

Frontier molecular orbitals
DFT was used to calculate the frontier molecular orbitals (FMOs, Fig. 7), which give important details of how a molecule interacts with other species, for example in terms of molecular reactivity and the ability of a molecule to absorb light. From the highest occupied molecular orbital (HOMO) electrons can be donated to the lowest unoccupied molecular orbital (LUMO). Moreover, the energy of the HOMO is directly related to the ionization potential, while the LUMO energy is directly related to the electron affinity, and the resulting energy difference (or energy gap) between HOMO and LUMO gives information about the stability of a molecule. In the case where the energy gap is small, the molecule is highly polarizable and has a high chemical reactivity. By using the HOMO and LUMO energy values of a molecule, its electronegativity (c), chemical hardness (   The frontier molecular orbitals (HOMO-LUMO) and the resulting band gap of the title molecule. molecule were calculated at the DFT/B3LYP level using the 6-311++G(d,p) basis set ( Table 1). The values of h and s are significant for the evaluation of both reactivity and stability. The electron transition from the HOMO to the LUMO energy level is shown in Fig. 7. The energy band gap [ÁE = E LUMO À E HOMO ] of the molecule is 4.8208 eV, the frontier molecular orbital energies E HOMO and E LUMO being À6.4559 and À1.6351 eV, respectively. The high value of the band gap (4,8208 eV) indicates the relatively high stability of the title molecule.

Synthesis and crystallization
The reaction scheme to yield the title compound is shown in Fig. 8. To a mixture of 4.32 g (20 mmol) 2-amino-5-bromobenzoic acid and 2.72 g (32 mmol) pyrrolidin-2-one, 21.8 g (13 ml) (d = 1.675) (0.142 mol) of phosphoroxychloride were added dropwise over 1 h at 273-275 K. The reaction mixture was then heated at 368-371 K for 2 h, it was subsequently cooled and finally poured over ice. The temperature of the mixture was kept at around 273-275 K. When the reaction mixture was completely decomposed, it was brought to pH = 10-11 with 25% wt ammonium hydroxide solution. The lightyellow precipitate was filtered off, dried and recrystallized from methanol. The yield of the product was 4.35 g (82%), m.p. 431-433 K (literature, m.p. = 430-431 K;Shakhidoyatov, 1983).

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.