Crystal structure, DFT study and Hirshfeld surface analysis of 1-nonyl-2,3-dihydro-1H-indole-2,3-dione

The dihydroindole portion is planar and the nonyl substituent is in an ‘extended’ conformation. In the crystal, the nonyl chains intercalate aided by pairwise C—H⋯O hydrogen bonds and the dihydroindoledione units are associated through additional C—H⋯O hydrogen bonds to form micellar blocks. The blocks are linked through π-stacking interactions between the six-membered rings of the dihydroindole units.


Chemical context
Indoline-2,3-dione or indole-1H-2,3-dione, commonly known as isatin, is a well-known natural product found in plants of genus Isatis and in Couropita guianancis aubl (Da Silva et al., 2001). It has also been isolated as a metabolic derivative of adrenaline in humans (Almeida et al., 2010). It was first obtained as an oxidation product of indigo in the early 19th century, and its current structure was proposed by Kekulé (1869). Isatin is a core constituent of many alkaloids (Trost et al., 2009) and drugs (Aboul-Fadl et al., 2010) as well as dyes (Domé nech et al., 2009), pesticides and analytical reagents. Isatin derivatives possess diverse activities such as antibacterial (Kassab et al., 2010), antiviral (Jarrahpour et al., 2007), anti-HIV (Sriram et al., 2006), anticancer (Gü rsoy et al., 2003) and anti-inflammatory (Sridhar et al., 2001) activities. As a continuation of our research work devoted to the development of isatin derivatives (Ben-Yahia et al., 2018;Rayni et al., 2019), we report in this work the synthesis and the Hirshfeld surface analysis of a new indoline-2,3-dione derivative obtained by the action of nonyl bromide on isatin under phase-transfer catalysis conditions.

Structural commentary
The molecular structure of the title compound is shown in Fig. 1. The dihydroindole skeleton is planar to within 0.0286 (8) Å (r.m.s. deviation of the fitted atoms = 0.0157 Å ) with Cl being the furthest from the mean plane. The nonyl chain is in an 'extended' conformation and is well out of the mean plane of the dihydroindole unit, as indicated by the C1-N1-C9-C10 torsion angle of À69.94 (12) .

Figure 2
Detail of the intermolecular interactions. C-HÁ Á ÁO hydrogen bonds and -stacking interactions are shown, respectively, by black and orange dashed lines. H atoms not involved in hydrogen bonds are omitted for clarity.

Figure 3
Packing viewed along the b-axis direction with intermolecular interactions depicted as in Fig. 2. H atoms not involved in hydrogen bonds are omitted for clarity.

Figure 1
The title molecule with the labelling scheme and 50% probability ellipsoids.

Calculation of the electronic structure
The structure in the gas phase of the title compound was optimized by means of density functional theory. The DFT calculation was performed using the hybrid B3LYP method, which is based on the idea of Becke and considers a mixture of the exact (HF) and DFT exchange utilizing the B3 functional, together with the LYP correlation functional (Becke, 1993;Lee et al., 1988;Miehlich et al., 1989). The B3LYP calculation was performed in conjunction with the def2-SVP basis set (Weigend & Ahlrichs, 2005). After obtaining the converged geometry, the harmonic vibrational frequencies were calculated on the same theoretical level to confirm that the number of imaginary frequencies is zero for the stationary point. Both the geometry optimization and the harmonic vibrational frequency analysis of the title compound were performed using the Gaussian 16 program (Frisch et al., 2016). The result of the B3LYP geometry optimization for the title compound (shown in Fig. 4) was compared to that of the crystallographic study with selected geometric parameters for the gas-phase and solid-phase structures summarized in Table 2. This shows that there is a clear discrepancy between the B3LYP-optimized geometry and the X-ray geometry. To quantify this, the openBabel program was then used to convert the experimental CIF file to a Gaussian .gjf input file (

Hirshfeld surface analysis
Both the definition of a molecule in a condensed phase and the recognition of distinct entities in molecular liquids and crystals are fundamental concepts in chemistry. Based on Hirshfeld's partitioning scheme, Spackman et al. (1997) proposed a method to divide the electron distribution in a crystalline phase into molecular fragments (Spackman & Byrom, 1997;McKinnon et al., 2004;Spackman & Jayatilaka, 2009 The d norm Hirshfeld surface of the title compound (red: negative, white: zero, blue: positive; scale: À0.2101 to 1.3375 a.u.). Table 2 The B3LYP-optimized and X-ray structural parameters (Å , ) for the title compound.

Figure 4
The B3LYP-optimized geometry of the title compound (bond lengths in Å , bond angles in ; carbon in gray, nitrogen in blue, oxygen in red and hydrogen in white). please improve resolution tive (positive) when intermolecular contacts are shorter (longer) than the van der Waals radii. The d norm value is mapped onto the Hirshfeld surface using red, white or blue colours. The red regions represent closer contacts with a negative d norm value while the blue regions represent longer contacts with a positive d norm value. The white regions represent contacts equal to the van der Waals separation and have a d norm value of zero. As depicted in Fig. 5

Synthesis and crystallization
To a solution of isatin (0.5 g, 3.4 mmol) dissolved in 25 ml of N,N-dimethylformamide, 1-bromooctane (0.7 ml, 3.4 mmol), potassium carbonate (0.61 g, 4.4 mmol) and a catalytic amount of tetra-n-butylammonium bromide (0.1 g, 0.4 mmol) were added. The mixture was stirred for 48 h and the reaction monitored by thin layer chromatography. The mixture was filtered and the solvent removed under vacuum. The solid obtained was recrystallized from ethanol to afford the title compound as orange-red crystals.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3.

Computing details
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: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008). Extinction correction: SHELXL2018 (Sheldrick, 2015b), Fc * =kFc[1+0.001xFc 2 λ 3 /sin(2θ)] -1/4 Extinction coefficient: 0.0114 (9) 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. 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.