Crystal structure, Hirshfeld surface analysis, crystal voids, interaction energy calculations and energy frameworks, and DFT calculations of 1-(4-methylbenzyl)indoline-2,3-dione

In the crystal of 1-(4-methylbenzyl)indoline-2,3-dione, a layer structure is generated by C—H⋯O hydrogen bonds and C—H⋯π(ring), π-stacking and C=O⋯π(ring) interactions.


Chemical context
Isatin derivatives have a biologically active heterocyclic moiety that comprises two cyclic rings, one of which is sixmembered and the other is five-membered (Rharmili et al., 2023a).Both the rings are planar.It constitutes an important class of heterocyclic compounds which, even when part of a complex molecule, possess a wide spectrum of biological activities (Rharmili et al., 2023b), such as anticancer (Esmaeelian et al., 2013), antioxidant (Andreani et al., 2010), antimalarial (Chiyanzu et al., 2005), anti-inflammatory (Sharma et al., 2016), analgesic (Prakash et al., 2012) and antianxiety (Medvedev et al., 2005).They have also been studied and been reported as efficient inhibitors against aluminium and steel corrosion (Abdellaoui et al., 2021).In a continuation of our ongoing research work devoted to the study of Oalkylation and N-alkylation reactions involving isatin derivatives (Rharmili et al., 2023b), we report herein the synthesis and the molecular and crystal structures of 1-(4-methylbenzyl) indoline-2,3-dione (Scheme 1) obtained by an alkylation reaction of 1H-indoline-2,3-dione using an excess of 4methylbenzyl bromide as an alkylating reagent and potassium carbonate in the presence of tetra-n-butylammonium bromide as catalyst in phase-transfer catalysis (PTC).Moreover, a Hirshfeld surface analysis, crystal voids, and interaction energy and energy frameworks calculations were performed.The molecular structure optimized by density functional theory (DFT) at the B3LYP/6-311G(d,p) level is compared with the experimentally determined molecular structure in the solid state.

Structural commentary
The indoline portion (Fig. 1) is planar to within 0.0097 (10) A (r.m.s.deviation of the fitted atoms = 0.0050 A ˚) and the mean plane of the C10-C15 ring is inclined to the above plane by 79.03 (3) � .The C7-C8 bond, at 1.5555 (18) A ˚, is longer than expected for that between two sp 2 C atoms but apppears typical for indoline-2,3-diones.Otherwise, the metrical parameters are unremarkable.

Hirshfeld surface analysis
In order to visualize the intermolecular interactions in the crystal of the title compound, (I), a Hirshfeld surface (HS) analysis (Hirshfeld, 1977;Spackman & Jayatilaka, 2009) was carried out using CrystalExplorer (Version 17.5; Turner et al., 2017).In the HS plotted over d norm (Fig. 4), 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 bright-red spots 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

Figure 5
View of the three-dimensional Hirshfeld surface of the title compound plotted over electrostatic potential energy 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 6
Hirshfeld surface of the title compound plotted over shape index.
The nearest-neighbour coordination environment of a molecule can be determined from the colour patches on the HS based on how close to other molecules they are.The Hirshfeld surface representations with the function d norm plotted onto the surface are shown for the H� � �H, H� � �C/ C� � �H and H� � �N/N� � �H interactions in Figs.8(a)-(c), respectively.The Hirshfeld surface analysis confirms the importance of H-atom contacts in establishing the packing.The large number of H� � �H, H� � �C/C� � �H and H� � �N/N� � �H interactions suggest that van der Waals interactions and hydrogen bonding play the major roles in the crystal packing (Hathwar et al., 2015).

Crystal voids
The strength of the crystal packing is important for determining the response to an applied mechanical force.If the crystal packing results in significant voids, then the molecules are not tightly packed and a small amount of applied external mechanical force may easily break the crystal.For checking the mechanical stability of the crystal, a void analysis was performed by adding up the electron densities of the spherically symmetric atoms contained in the asymmetric unit (Turner et al., 2011).The void surface is defined as an isosurface of the procrystal electron density and is calculated for the whole unit cell where the void surface meets the boundary of the unit cell and capping faces are generated to create an enclosed volume.The volume of the crystal voids [Figs.9(a) and 9(b)] and the percentage of free space in the unit cell are calculated as 120.52A ˚3 and 9.64%, respectively.Thus, the crystal packing appears compact and the mechanical stability should be substantial.

Interaction energy calculations and energy frameworks
The intermolecular interaction energies are calculated using the CE-B3LYP/6-31G(d,p) energy model available in Crys-talExplorer (Version 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 radius of 3.8 A ˚by default (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.

Figure 9
Graphical views of voids in the crystal packing of (I) (a) along the a-axis direction and (b) along the b-axis direction.(Mackenzie et al., 2017).Hydrogen-bonding interaction energies (in kJ mol À 1 ) were calculated to be [À 11.6 (E ele ), À 4.3 (E pol ), À 71.9 (E dis ), 46.4 (E rep ) and À 49.4 (E tot )] for the C4-H4� � �O2 and [À 5.4 (E ele ), À 3.9 (E pol ), À 24.7 (E dis ), 14.3 (E rep ) and À 21.3 (E tot )] for the C9-H9B� � �O2 hydrogenbonding interaction.Energy frameworks combine the calculation of intermolecular interaction energies with a graphical representation of their magnitude (Turner et al., 2015).Ener-gies between molecular pairs are represented as cylinders joining the centroids of pairs of molecules with the cylinder radius proportional to the relative strength of the corresponding interaction energy.Energy frameworks were constructed for E ele (red cylinders), E dis (green cylinders) and E tot (blue cylinders) [Figs. 10(a), 10(b) and 10(c)].The evaluation of the electrostatic, dispersion and total energy frameworks indicate that the stabilization is dominated via the dispersion energy contribution in the crystal structure of (I).

Database survey
We searched the Cambridge Structural Database (CSD) for N-substituted isatin derivatives using Version 5.42, which was last updated in May 2023 (Groom et al., 2016).Our search yielded 58 results, five of which were reports on the structure of isatin itself, and four of which focused on the structure of N-methylisatin.Out of these findings, 13 structures contained an alkyl chain with two or more C atoms.The compound that showed the closest resemblance to the title compound was indole-2,3-dione (Wang et al., 2010).

Figure 10
The energy frameworks for a cluster of molecules of the title compound, viewed down the a-axis direction, showing (a) electrostatic energy, (b) dispersion energy and (c) total energy diagrams.The cylindrical radius is proportional to the relative strength of the corresponding energies and they were adjusted to the same scale factor of 80 with a cut-off value of 5 kJ mol À 1 within 2 � 2 � 2 unit cells.
as implemented in GAUSSIAN09 (Frisch et al., 2009).The resulting optimized parameters, including bond lengths and angles, exhibited satisfactory agreement with the experimental structural data (Table 2).The most significant disparities between the calculated and experimental values were observed for the O1-C7 and N1-C9 (0.04 A ˚), and C1-C2 and O2-C8 (0.03 A ˚) bond lengths.Additionally, notable disparities were noted in the O1-C7-C8 bond angle (3.05 � ) and the C7-N1-C9-C10 torsion angle (0.85 � ).For instance, some reported bond lengths for O1-C7 and N1-C9 were fuond to vary by 0.03 and 0.01 A ˚, respectively, for 1-(12bromododecyl)indoline-2,3-dione (Rharmili et al., 2023a).These differences may be attributed to the fact that these calculations pertain to the isolated molecule, while the experimental results correspond to interacting molecules in the crystal lattice, where intra-and intermolecular interactions with neighbouring molecules are present.

Synthesis and crystallization
To a solution of 1H-indoline-2,3-dione (2 mmol) in dimethylformamide (DMF, 20 ml) were added 4-methylbenzyl bromide (2.2 mmol), K 2 CO 3 (1.5 mmol) and tetra-n-butylammonium bromide (TBAB; 0.5 mmol).The reaction mixture was stirred at room temperature in DMF for 12 h.After removal of the formed salts, the solvent was evaporated under reduced pressure and the residue obtained was dissolved in dichloromethane.The organic phase was dried over Na 2 SO 4 and then concentrated in vacuo.A pure compound was obtained after

Special details
Experimental.The diffraction data were obtained from 7 sets of frames, each of width 0.5° in ω, collected with scan parameters determined by the "strategy" routine in APEX4.The scan time was 7.5 sec/frame.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).All were included as riding contributions with isotropic displacement parameters 1.2 -1.5 times those of the attached atoms. Fractional

Figure 2 A
Figure 2 A portion of one layer, viewed along the c-axis direction, with C-H� � �O hydrogen bonds and C-H� � ��(ring) and �-stacking interactions depicted, respectively, by black, green and orange dashed lines.The C O� � ��(ring) interactions are depicted by pink dashed lines and noninteracting H atoms have been omitted for clarity.

Figure 3
Figure 3The packing viewed along the b-axis direction giving edge views of four layers.C-H� � �O hydrogen bonds and C-H� � ��(ring) and �-stacking interactions are depicted, respectively, by black, green and orange dashed lines, while the C O� � ��(ring) interactions and non-interacting H atoms have been omitted for clarity.
Fig. 5.The blue regions indicate the positive electrostatic potential (hydrogenbond donors), while the red regions indicate the negative electrostatic potential (hydrogen-bond acceptors).The shape index of the HS is a tool to visualize the �-� stacking by the presence of adjacent red and blue triangles; if there are no adjacent red and/or blue triangles, then there are no �-� interactions.Fig. 6 clearly suggests that there are �-� interactions in (I).The overall two-dimensional fingerprint plot, Fig. 7(a), and those delineated into H� � �H, H� � �C/C� � �H, H� � �O/O� � �H, C� � �O/O� � �C, C� � �C, N� � �C/C� � �N, N� � �O/ O� � �N and H� � �N/N� � �H (McKinnon et al., 2007) are illustrated in Figs.7(b)-(i), respectively, together with their relative contributions to the Hirshfeld surface.The most abundant interaction is H� � �H, contributing 43.0% to the overall crystal packing, which is reflected in Fig. 7(b) as the widely scattered points of high density due to the large hydrogen content of the molecule with the tip at d e = d i = 1.20 A ˚.In the presence of C-H� � �� interactions, the H� � �C/ C� � �H contacts, contributing 25.0% to the overall crystal packing, are reflected in Fig. 7(c) with the tips at d e + d i = 2.71 A ˚.The symmetrical pair of spikes resulting in the fingerprint plot delineated into H� � �O/O� � �H contacts [Fig.7(d)] has a 22.8% contribution to the HS with the tips at d e + d i = 2.29 A ˚.The symmetrical pair of tiny wings resulting in the fingerprint plot delineated into C� � �O/O� � �C contacts [Fig.7(e)], with a 4.1% contribution to the HS, is viewed with the tips at d e + d i = 3.29 A ˚.The C� � �C contacts [Fig.7(f)] have an arrow-shaped distribution of points, with the tip at d e = d i = 1.68A ˚. Finally, the C� � �N/N� � �C [Fig.7(g)], N� � �O/O� � �N [Fig.7(h)] and H� � �N/N� � �H [Fig.7(i)] contacts with 1.0, 0.2 and 0.1% contributions, respectively, to the HS have very low distributions of points.

Figure 4
Figure 4View of the three-dimensional Hirshfeld surface of the title compound plotted over d norm .

Figure 8 The
Figure 8 The Hirshfeld surface representations with the function fragment patch plotted onto the surface for (a) H� � �H, (b) H� � �C/C� � �H and (c) H� � �O/O� � �H interactions.

Table 2
Comparison of the selected (X-ray and DFT) geometric data (A ˚, � ).

Table 3
Experimental details.