Methyl 3′-benzyl-4′-(2,4-di­chloro­phen­yl)-1′-methyl-2-oxo­spiro­[indoline-3,2′-pyrrolidine]-3′-carboxyl­ate

S Karthikeyan; P Narayanan; K Sethusankar; Anthonisamy Devaraj; Manickam Bakthadoss

doi:10.1107/S1600536814003523

. 2014 Feb 22;70(Pt 3):o335. doi: 10.1107/S1600536814003523

Methyl 3′-benzyl-4′-(2,4-dichlorophenyl)-1′-methyl-2-oxospiro[indoline-3,2′-pyrrolidine]-3′-carboxylate

S Karthikeyan ^a, P Narayanan ^a, K Sethusankar ^a,^*, Anthonisamy Devaraj ^b, Manickam Bakthadoss ^b

PMCID: PMC3998484 PMID: 24765030

Abstract

In the title compound, C₂₇H₂₄Cl₂N₂O₃, the indole ring system is essentially planar, with a maximum deviation of 0.082 (2) Å for the carbonyl C atom. It makes a dihedral angle of 88.53 (6)° with the mean plane of the 4-methylpyrrolidine ring, which adopts an envelope conformation with the N atom at the flap position. The molecular structure is stabilized by intramolecular C—H⋯O hydrogen bonds, which generate S(6) and S(7) ring motifs, and an intramolecular π–π interaction involving the benzyl and dichloro-substituted benzene rings [centroid–centroid distance = 3.6291 (11) Å]. In the crystal, molecules are linked via N—H⋯O hydrogen bonds, forming C(7) chains running parallel to [10-1].

Related literature

For the biological activity of spiro-oxindole derivatives, see: Hilton et al. (2000 ▶). For a related crystal structure, see: Karthikeyan et al. (2014 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). For graph-set motifs, see: Bernstein et al. (1995 ▶). For bond-length distortions in small rings, see: Allen (1981 ▶).

Experimental

Crystal data

C₂₇H₂₄Cl₂N₂O₃
M _r = 495.38
Monoclinic,
a = 12.7051 (5) Å
b = 14.1724 (6) Å
c = 14.0322 (6) Å
β = 109.424 (2)°
V = 2382.85 (17) Å³
Z = 4
Mo Kα radiation
μ = 0.31 mm⁻¹
T = 293 K
0.30 × 0.28 × 0.25 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
27865 measured reflections
6466 independent reflections
4356 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.124
S = 1.00
6466 reflections
309 parameters
H-atom parameters constrained
Δρ_max = 0.41 e Å⁻³
Δρ_min = −0.49 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536814003523/su2699sup1.cif

e-70-0o335-sup1.cif^{(24.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814003523/su2699Isup2.hkl

e-70-0o335-Isup2.hkl^{(316.5KB, hkl)}

Click here for additional data file.^{(3.5KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814003523/su2699Isup3.cml

CCDC reference: 888482

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C18—H18B⋯O1	0.97	2.31	3.046 (2)	132
C24—H24⋯O3	0.93	2.52	3.155 (2)	126
N2—H2A⋯O2ⁱ	0.86	2.07	2.924 (2)	170

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank Dr Babu Varghese, SAIF, IIT, Chennai, India, for the data collection.

supplementary crystallographic information

1. Comment

The derivatives of spiro-oxindole ring systems are used as antimicrobial, antitumor agents and as inhibitors of the human NKI receptor besides being found in a number of alkaloids like horsifiline, spirotryprostatin and (+)elacomine (Hilton et al., 2000).

The molecular structure of the title compound is illustrated in Fig 1. In the molecule, there are C—H···O hydrogen bonds forming S(6) and S(7) ring motifs (Bernstein et al., 1995), and a π···π interaction [Cg(1)···Cg(2) = 3.6291 (11) Å, where Cg1 and Cg2 are the centroids of rings C1—C6 and C19—C24, respectively]. The indole ring system is essentially planar with a maximum deviation of 0.082 (2) Å for atom C10. The mean plane of this indole ring system forms a dihedral angle of 88.53 (6)° with the 4-methylpyrrolidine ring mean plane. The latter forms a dihedral angle of 83.37 (9)° with the benzyl ring which shows that they are almost orthogonal. Atom O1 significantly deviates from the mean plane of the indole ring system by -0.2251 (15) Å. The molecular dimensions in the title compound are in excellent agreement with those reported for the 3-bromophenyl derivative (Karthikeyan et al., 2014).

The spiro-pyrrolidine ring (N1/C7-C9/C17) adopts an envelope conformation with atom N1 at the flap. The distance to the flap position from the mean plane of the four C atoms is 0.2476 (16) Å; the ring puckering parameters (Cremer & Pople, 1975) are Q₂ = 0.3917 (18) Å and φ₂ = 2.8 (3)°. The central spiro-pyrrolidine ring mean plane is perpendicular to the dichlorophenyl ring with a dihedral angle of 81.66 (9)°. The carbonyl group, C10═O2, and the benzyl ring (C18-C24) ring have an (+)anti-clinal conformation with torsion angle (C18—C17—C25—O2) of 146.81 (16)°.

In the benzene ring (C11—C16) of the indole ring system, the expansion of the ipso angles at C11, C13 and C14 [121.71 (19), 121.1 (2) and 120.8 (2)°, respectively] and contraction of the apical angles at C12, C15 and C16 [117.9 (2), 119.13 (18) and 119.43 (16)°, respectively] are caused by the fusion of the smaller pyrrole ring to the six-membered benzene ring and the strain is taken up by the angular distortion rather than by bond-length distortions (Allen, 1981). The carboxyl group and oxindole ring system are (-)anti-clinal to each other with torsion angle (C9—C17—C25—O2) of -92.85 (18)°.

In the crystal, molecules are linked via N-H···O hydrogen bonds forming C(7) chains running parallel to [1 0 -1]; see Fig. 2 and Table 1.

2. Experimental

A mixture of (E)-methyl 2-benzyl-3-(2,4-dichlorophenyl)acrylate (2 mmol), isatin (2 mmol) and sarcosine (2 mmol) in acetonitrile (8 ml) was refluxed for 12 h. After the completion of the reaction as indicated by TLC, the reaction mixture was concentrated. The resulting crude mass was diluted with water (10 ml) and extracted with ethyl acetate (3 × 10 ml). The combined organic layers were washed with brine (2 × 10 ml) and dried over anhydrous Na₂SO₄. The organic layer was concentrated and the residue purified by column chromatography on silica gel (Acme 100–200 mesh), using ethyl acetate:hexanes (2:8) to afford the title compound as a colourless solid in (65%) yield. Block-like colourless crystals were obtained by slow evaporation of a solution in CHCl₃.