Crystal structure of 2′-[(2′,4′-difluorobiphenyl-4-yl)carbonyl]-1′-phenyl-1′,2′,5′,6′,7′,7a’-hexahydrospiro[indole-3,3′-pyrrolizin]-2(1H)-one

In the title spiro-pyrrolizidine derivative, the difluorophenyl group is oriented at an angle of 54.3 (1)° with respect to the oxindole moiety. In the crystal, molecules are linked via N—H⋯O hydrogen bonds, forming dimers with an (8) motif.

In the title pyrrolizidine derivative, C 33 H 26 F 2 N 2 O 2 , both pyrrolidine rings of the pyrrolizidine moiety adopt an envelope conformation. The difluorophenyl group is oriented at an angle of 54.3 (1) with respect to the oxindole moiety. The crystal packing features an N-HÁ Á ÁO hydrogen bond, which forms an R 2

Chemical context
Isatin (1H-indole-2,3-dione) has been exploited extensively as a key intermediate in organic multicomponent reactions due to its antibacterial , antifungal (Amal Raj et al., 2003;Dandia et al., 2006), antiviral (Quenelle et al., 2006), anti-HIV (Sriram et al., 2006;Pandeya et al., 2000), antimycobacterial (Feng et al., 2010), anticancer (Gursoy & Karali, 2003), anti-inflammatory ) and anticonvulsant (Verma et al., 2004) activities. The versatile reactivity of isatin has led to the synthesis of a number of isatin-based spiro compounds. Chalcones are precursors and valuable intermediates for the synthesis of many biologically important heterocyclic compounds. Therefore, the combination of chalcone with isatin and secondary amino acids provides spirooxindolopyrrolizidine derivatives with enhanced biological activities. In view of the many interesting applications of pyrrolizidine derivatives, we synthesized the title compound and report herein its crystal structure.

Figure 3
The inversion dimer formed via N-HÁ Á ÁO hydrogen bonds (dashed lines). For clarity H atoms not involved in these hydrogen bonds have been omitted.

Supramolecular features
The geometry of interactions observed in this structure are given in Table 1. In the crystal, molecules associate via N-HÁ Á ÁO hydrogen bonds into inversion dimers, generating an R 2 2 (8) motif; see

Synthesis and crystallization
To a solution of isatin (1 mmol) and L-proline (1 mmol) in methanol (25 ml), 1-[4-(2,4-difluorophenyl)phenyl]3-phenylprop-2-en-1-one (1 mmol) was added and the solution was refluxed for 6-8 h. The completion of reaction was monitored by thin layer chromatography. After completion, the reaction mixture was poured onto crushed ice. The precipitate obtained was filtered and dried at room temperature. Suitable crystals were obtained by slow evaporation of a solution of the title compound in acetonitrile at room temperature. The packing of the title compound, showing the C-HÁ Á Á andinteractions as dashed lines. For clarity H atoms not involved in these interactions have been omitted.

Figure 4
The packing of the title compound, viewed approximately down the a axis. C-HÁ Á ÁO interactions are shown as dashed lines (see Table 1). For clarity, H atoms not involved in these interactions have been omitted.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms were placed in idealized positions and allowed to ride on their parent atoms: C-H = 0.93-0.97 Å , with U iso (H) = 1.5U eq (C) for methyl H atoms and 1.2U eq (C) for other H atoms. Atom C18 is disordered over two positions, with the major component having 0.571 (4) occupancy. Pairs of C-C distances were restrained to 1.54 (1) Å . The temperature factor of C18 0 was set to that of C18 with the EADP instruction of SHELXL2014/7 (Sheldrick, 2015).

Computing details
Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and PLATON (Spek, 2009); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015) and PLATON (Spek, 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.