Crystal structure, Hirshfeld surface analysis and DFT studies of 5-bromo-1-{2-[2-(2-chloroethoxy)ethoxy]ethyl}indoline-2,3-dione

The title compound consists of the 5-bromoindoline-2,3-dione unit linked by a 1-{2-[2-(2 chloroethoxy)ethoxy]ethyl} moiety. In the crystal, intermolecular C—HBrmind⋯ODio, C—HBrmind⋯OEthy, C—HChlethy⋯ODio and C—HChlethy⋯OChlethy (Brmind = bromoindoline, Dio = dione, Ethy = ethoxy and Chlethy = chloroethoxy) hydrogen bonds link the molecules into a three-dimensional structure, enclosing (8), (12), (18) and (22) ring motifs. The π–π contacts between the five-membered dione rings may further stabilize the structure.


Chemical context
Heterocycles are a class of chemical compounds in which one atom or more than one carboxyl group is replaced by a heteroatom such as oxygen, nitrogen, phosphorus or sulfur. They are very interesting chemical compounds because of their potential applications in different fields. The most common heterocycles contain nitrogen and oxygen (Pathak & Bahel, 1980;Naik & Malik, 2010;Srivalli et al., 2011). The chemistry of nitrogen compounds is the preferred source for a large number of study subjects in the laboratory. The N atom is present in several natural molecules of pharmacological interest, so many methods have been developed to access nitrogen compounds, especially heterocyclic compounds. Given the biological interest of heterocyclic compounds, we have been interested in synthesizing new polyfunctional heterocyclic systems capable of presenting potential applications. The chemistry of isatin is already well documented due to its wide range of applications, especially in organic synthetic chemistry and medicinal chemistry. The first reports on the syntheses of isatin and isatin-based derivatives can be traced back to the first half of the 19th century, and almost one hundred years after those publications, the review 'The Chemistry of Isatin' showed the versatility of this molecular fragment. This reaction is also used for the synthesis of natural products, such as sugar derivatives (DeShong et al., 1986),lactams (Kametani et al., 1988), amino acids (Annuziata et al., 1986 and alkaloids (Asrof Ali et al., 1988), and products with pharmacological interest, such as pyrazolines, which have several biological activities (Araino et al., 1996;Harrison et al., 1996). As a continuation of our research devoted to the development of substituted 5-bromoindoline-2,3-dione derivatives, we report herein the synthesis and molecular and crystal structures, along with the Hirshfeld surface analysis and the density functional theory (DFT) computational calculations carried out at the B3LYP/6-311G(d,p) level, of a 5-bromoindoline-2,3-dione derivative by the alkylation reaction of 5-bromo-1H-indole-2,3-dione under phase-transfer catalysis conditions using tetra-n-butylammonium bromide (TBAB) as catalyst and potassium carbonate as base, leading to the title compound, (I).

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 CrystalExplorer17.5 (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 the 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 brightred spots appearing near atoms O1, O2 and O4, and H atoms H2, H14A and H14B, indicate their roles as the respective donors and/or 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), as shown in Fig View of the three-dimensional Hirshfeld surface of the title compound plotted over d norm in the range À0.3481 to 1.0316 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-3G 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. Table 2 Summary of short interatomic contacts (Å ).

Figure 5
Hirshfeld surface of the title compound plotted over shape-index.
( Fig. 6a) Fig. 6(b) as widely scattered points of high density due to the large hydrogen content of the molecule with the tip at d e = d i $1.08 Å , due to the short interatomic HÁ Á ÁH contacts ( Table 2). The pair of characteristic wings resulting in the fingerprint plot delineated into HÁ Á ÁO/OÁ Á ÁH contacts (Fig. 6c), with a 23.5% contribution to the HS, arises from the HÁ Á ÁO/OÁ Á ÁH contacts (Table 2) and is viewed as a pair of spikes with the tips at d e + d i = 2.10 Å . The pairs of scattered points of wings resulting in the fingerprint plots delineated into HÁ Á ÁBr/BrÁ Á ÁH (Fig. 6d) and HÁ Á ÁCl/ClÁ Á ÁH (Fig. 6e) (Table 2). In the absence of C-HÁ Á Á interactions, with a pair of characteristic wings resulting in the fingerprint plot delineated into HÁ Á ÁC/CÁ Á ÁH contacts (Fig. 6f), a 10.2% contribution to the HS, arises from the HÁ Á ÁC/CÁ Á ÁH contacts (Table 2) and is seen as a thick pair of spikes with the tips at d e + d i = 2.82 Å . The pair of characteristic wings resulting in the fingerprint plot delineated into OÁ Á ÁC/CÁ Á ÁO contacts (Fig. 6g), with a 4.0% contribution to the HS, arises from the OÁ Á ÁC/CÁ Á ÁO contacts (Table 2) and is seen as a pair of spikes with the tips at d e + d i = 3.05 Å . The CÁ Á ÁC contacts (Fig. 6h), with a 2.6% contribution to the HS, have a nearly arrowshaped distribution of points arising from the CÁ Á ÁC contacts (Table 2) and is seen with the tip at d e = d i $1.62 Å . Finally, the pair of scattered points of wings resulting in the fingerprint plot delineated into OÁ Á ÁCl/ClÁ Á ÁO (Fig. 6i)   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, (I), in the gas phase was generated theoretically via density functional theory (DFT) using standard B3LYP functional and 6-311G(d,p) basis-set calculations (Becke, 1993), as implemented in GAUSSIAN09 (Frisch et al., 2009). The theoretical and experimental results were in good agreement (Table 4) parameters for quantum chemistry. When the energy gap is small, the molecule is highly polarizable and has high chemical reactivity. The electron transition from the HOMO to the LUMO energy level is shown in Fig. 8. The HOMO and LUMO are localized in the plane extending from the whole 1-{2-[2-(2-chloroethoxy)ethoxy]ethyl}-5-bromoindoline-2,3dione ring. The energy band gap (ÁE = E LUMO À E HOMO ) of the molecule was about 6.5402 eV, and the frontier molecular orbital energies, i.e. E HOMO and E LUMO , were À7.4517 and À0.9115 eV, respectively.

Refinement
The experimental details, including the crystal data, data collection and refinement, are summarized in Table 3. H atoms were positioned geometrically, with C-H = 0.93 and 0.97 Å for aromatic and methylene H atoms, respectively, and constrained to ride on their parent atoms, with U iso (H) = 1.2U eq (C). During the refinement process, the disordered chloroethoxyethoxyethyl side-chain atoms were refined with a major-minor occupancy ratio of 0.665 (8):0.335 (6).

Figure 8
The energy band gap of the title compound. Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009). 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. Refinement. At the end of the refinement, it remained some residual electronic density pics around O4 and C12. suggesting a disorder. We modeled this disorder considering two positions with following occupancies : 0.665 (7) and 0.335 (7). The R1(Fo > 4sig(Fo)) factor decreased from 5.96% to 3.76%.