5-Chloro-1-(4-methoxybenzyl)indoline-2,3-dione

In the title compound, C16H12ClNO3, an arm-like 4-methoxybenzene links to 5-chloroindoline-2,3-dione through a methylene group, with a dihedral angle between the mean planes of the benzene ring and the indole moiety of 88.44 (8)°. In the crystal, weak intermolecular C—H⋯O and π–π stacking interactions [centroid–centroid distance = 3.383 (3) Å] link the molecules together to form a three-dimensional framework.


Comment
It has been reported that the introduction of a benzyl or naphthylmethyl group into the N1 position of isatin can significantly increase its cytotoxicity against a wide range of human tumor cell lines (Vine et al., 2007;Matesic et al., 2008;Penthala et al., 2010). The studies on the structure-activity relationship of these derivatives also revealed that the 4-methoxybenzyl is one of the most favorable groups for the enhancement of their relative cytotoxicity (Vine et al., 2007). To explore these isatin-based antitumor agents, we synthesized the title compound 5-chloro-1-(4-methoxybenzyl)-indoline-2,3-dione. Herein, we report the structure of the title compound.
In the title compound, C 16 H 12 ClNO 3 , the indoline and methoxybenzene moieties are linked by a methylene group with a C5-C7(methylene)-N1 angle of 113.86 (2)° ( Fig. 1). The mean planes of the benzene ring and of the indole-2,3-dione exhibit a dihedral angle of 88.44 (8)°. The molecules stake along the a axis and interconnect through π-π interaction between the adjacent indole-2,3-dione moieties, forming a chain structure, as shown in Fig. 2. The distance between the two planes is 3.383 (3) Å. The parallel chains with the stacking molecules are further interconnected through two types of C-H···O(=C) ineractions: C-H(methyl)···O and C-H(benzene)···O (Table 1). The D···A distances vary from 3.391 (3) to 3.537 (4) Å, while the D-H···A angles lie within the 146-159° range. By these cooperative weak intermolecular interactions, a three-dimensional framework is constructed (Fig. 2).

Experimental
To an ice-bath cooled solution of 5-chloro-indoline-2,3-dione (0.36 g, 2 mmol) in N,N-dimethylformamide (20 ml) was added potassium carbonate (0.33 g, 2.4 mmol) and potassium iodide (0.07 g, 0.4 mmol) followed by 4-methoxybenzyl chloride (0.32 ml, 2.2 mmol). The reaction mixture was stirred at 110 °C for 3 h. After cooling to room temperature, the reaction mixture was poured into ice water (80 ml). The resulting precipitate was separated by filtration and purified by column chromatography on silica gel with dichloromethane as an eluent to give the title compound (R f = 0.81, dichloromethane; m.p. 152-153 °C; yield 72%). The red crystals of the title compound were obtained by slow evaporation from the solution of dichloromethane/ethanol 8:2 (v/v) at room temperature.

Refinement
All H atoms were discernible in the difference electron density maps. Nevertheless, the hydrogen atoms were placed into idealized positions and allowed to ride on the carrier atoms, with C-H = 0.93 and 0.97 Å [U iso (H) = 1.2U eq (C)] for aromatic and methylene H atoms, respectively, and with C-H = 0.96 Å [U iso (H) = 1.5U eq (C)] for methyl H atoms. The Flack parameter is -0.01 (7) in the non-centrosymmetric refinement (1514 Friedel pairs).
supplementary materials sup-2 Figures   Fig. 1. The title molecule with the atomic numbering scheme. The displacement ellipsoids are shown at the 30% probability level, while the hydrogen atoms are shown as rods of arbitrary radius. Fig. 2. View down the a axis of the packing structure of the title compound. The red dashed lines indicate the intermolecular C-H···O interactions, while the π-π stacking interactions are omitted for clarity. Symmetry codes: (i) x + 1/2, -y + 1/2, z; (ii) -x + 1, -y + 1, z -1/2.