Crystal structure and Hirshfeld analysis of diethyl (2E,2′E)-3,3′-[1-(8-phenylisoquinolin-1-yl)-1H-indole-2,7-diyl]diacrylate

In the molecule of title compound, intramolecular π–π interactions between the indole unit and benzene ring help to establish the clip-shaped conformation of the molecule. In the crystal, the molecules are assembled into two-dimensional layers via C—H⋯O hydrogen bonds, π–π and C—H⋯π interactions.

The molecule of title compound, C 33 H 28 N 2 O 4 , comprises an indole unit (A), an isoquinoline moiety (B) and a benzene ring (C). The dihedral angles between these groups are A/B = 57.47 (1), A/C = 18.48 (1) and B/C = 57.97 (1) . The ethyl acrylate group at the 2-position is nearly co-planar with the indole unit [3.81 (2) ], while that at the 7-position is distinctly non-coplanar [52.64 (1) ]. Intramolecularinteractions between the indole unit and benzene ring help to establish the clip-shaped conformation of the molecule. In the crystal, the molecules are assembled into two-dimensional layers via C-HÁ Á ÁO hydrogen bonds,and C-HÁ Á Á interactions. Hirshfeld surface analysis illustrates that the greatest contributions are from HÁ Á ÁH (63.2%), CÁ Á ÁH/HÁ Á ÁC (15.4%) and OÁ Á ÁH/HÁ Á ÁO (14.8%) contacts. The terminal C 2 H 5 group of one of the ethyl acrylate side chains is disordered over two positions of equal occupancy.

Chemical context
As a type of N-containing heterocyclic compound, indoles derivatives are recognized as a privileged structural motif and are widely found in naturally occurring and synthetic molecules with significant biological activity, such as alkaloids, agrochemicals, and drugs (Sharma et al., 2010;Vargas et al., 2018). In particular, drugs containing indole subunits exhibit various activities, such as anti-bacterial (Liu, Lauro et al., 2017), anti-fungal (Xu et al., 2016), anti-viral (Zhang et al., 2015), anti-proliferative (Cheng et al., 2019), anti-inflammatory (Mazzotta et al., 2020), anti-tumor (Li et al., 2007), analgesic (Jin et al., 2021), and a large number of indole-based drugs have been marketed (Mir et al., 2021;Hussain et al., 2020), which has made great contributions to human health. Methods for the synthesis of functionalized indoles have therefore attracted a lot of attention over the past few decades. Among them, transition-metal-catalysed direct C-H activation of the indole framework itself has emerged as a fascinating avenue to afford functionalized indole derivatives on account of its atom economy and simplified procedure (Sandtorv, 2015;Liu, Zhao& Wu, 2017;Jagtap & Punji, 2020). On the other hand, because of the much higher reactivity of the 3-position than the 2-position and in turn than the sites in the six-membered ring (Joule et al., 2000;Fanton et al., 2010), studies on the synthesis of 2,7-disubstituted indole derivatives have scarcely been reported. Kumar and Sekar employed pyrimidine as a directing group to synthesize 2-acyl indoles and 2,7-diacyl indoles using a Pd catalyst (Kumar & Sekar, 2015). Herein, the synthesis, crystal structure and Hirshfeld analysis of the title compound is reported.

Hirshfeld Surface analysis
A Hirshfeld surface analysis was performed and the associated two-dimensional fingerprint plots were generated using Crystal Explorer (Turner et al., 2017), with a standard resolution of the three-dimensional d norm surfaces plotted over a fixed color scale of À0.1861 (red) to 1.7889 (blue) a.u. (Fig. 4). The packing of the title compound showing the two-dimensional layers formed by C-HÁ Á ÁO hydrogen bonds (dashed lines). Table 1 Hydrogen-bond geometry (Å , ).

Figure 3
Partial packing diagram of the title compound, showing theand C-H-interactions (red dashed lines).

Figure 1
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level showing the intramolecular and C-HÁ Á Á interactions as dashed lines.
The red spots symbolize short contacts and negative d norm values on the surface correspond to the C-HÁ Á ÁO hydrogen bonds described above. Two-dimensional fingerprint plots for the HÁ Á ÁH, HÁ Á ÁC/CÁ Á ÁH, and HÁ Á ÁO/OÁ Á ÁH contacts are presented in Fig. 5. At 63.2%, the largest contribution to the overall crystal packing is from HÁ Á ÁH interactions, which are located in the middle region of the fingerprint plot. HÁ Á ÁC/ CÁ Á ÁH contacts contribute 15.4%, and the HÁ Á ÁO/OÁ Á ÁH contacts contribute 14.8% to the Hirshfeld surface, both resulting in a pair of characteristic wings.

Figure 4
Hirshfeld surfaces of the title compound mapped over d norm .

Figure 5
The two-dimensional fingerprint plots for the title compound   the tube was purged with O 2 three times, followed by addition of ethyl acrylate (1.0 mmol) and anhydrous DCE (DCE = 1,2dichloroethane;1 mL). The formed mixture was stirred at 353 K under Ar for 24 h as monitored by TLC. The solution was then cooled to room temperature, and the solvent was removed under vacuum. The crude product was purified by column chromatography on silica gel to afford the pure product (55% yield). The recrystallization of the title compound in methanol afforded yellow block-shaped crystals. The synthesis is shown in Fig. 6.

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ. (