Crystal structure of ethyl 1′,5-dimethyl-2′′,3-dioxo-3H-dispiro[benzo[b]thiophene-2,3′-pyrrolidine-2′,3′′-indoline]-4′-carboxylate

The title compound, C23H22N2O4S, crystallized with two independent molecules (A and B) in the asymmetric unit. They have very similar conformations with the pyrrolidine ring having a twisted conformation, on the Cspiro—Cspiro bond, in both molecules. In molecule A, the mean planes of the benzothiophene and indoline ring systems are inclined to the mean plane of the pyrrolidine ring by 87.59 (10) and 84.51 (11)°, respectively, and to one another by 72.69 (7)°. The corresponding angles in molecule B are 87.15 (10), 84.58 (10) and 72.07 (7)°, respectively. In the crystal, the A and B molecules are linked to one another by two N—H⋯O hydrogen bonds, forming a dimer. These dimers are linked via C—H⋯O hydrogen bonds, forming a three-dimensional structure.


S1. Comment
Indole derivatives exhibit antihepatitis B virus (Chai et al., 2006) and antibacterial (Nieto et al., 2005) activities. Indole derivatives have been found to exhibit antibacterial, antifungal (Singh et al., 2000) and antitumour activities (Andreani et al., 2001). Some of the indole alkaloids extracted from plants possess interesting cytotoxic, antitumour or antiparasitic properties (Quetin-Leclercq, 1994;Mukhopadhyay et al., 1981). Highly functionalized pyrrolidines have gained much interest in the past few years as they constitute the main structural element of many natural and synthetic pharmacologically active compounds (Waldmann, 1995). In the crystal, the A and B molecules are linked to one another by two N-H···O hydrogen bonds forming a dimer (Table   1 and Fig. 2). These dimers are linked via C-H···O hydrogen bonds forming a three-dimensional structure (Table 1 and
After completion of the reaction the solvent was evaporated under reduced pressure. The crude reaction mixture was dissolved in dichloromethane (2 × 50 ml) and washed with water followed by brine solution. The organic layer was separated and dried over sodium sulfate. After filtration the organic solvent was evaporated under reduced pressure. The product was separated by column chromatography using hexane and ethyl acetate (9:1) as an eluent to give a colorless solid. The product was dissolved in chloroform (3 ml) and heated for 2 min. The resulting solution was subjected to crystallization by slow evaporation of the solvent giving single crystals suitable for X-ray crystallographic studies.

S3. Refinement
N and C-bound H atoms were positioned geometrically and allowed to ride on their parent atoms: N-H = 0.86 Å, C-H = 0.93-0.98 Å with U iso (H) = 1.5U eq (C) for methyl H atoms and = 1.2U eq (N,C) for other H atoms.

Figure 1
The molecular structure of the two independent molecules (A and B) of the title compound, with atom labelling.
Displacement ellipsoids are drawn at the 30% probability level.
Special details Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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.