Methyl 5′′-chloro-1′,1′′-dimethyl-2,2′′-dioxodi­spiro­[indoline-3,2′-pyrrolidine-3′,3′′-indoline]-4′-carboxyl­ate

Piskala Subburaman Kannan; PanneerSelvam Yuvaraj; Karthikeyan Manivannan; Boreddy Siva Rami Reddy; Arunachalathevar SubbiahPandi

doi:10.1107/S1600536813011501

. 2013 May 4;69(Pt 6):o825–o826. doi: 10.1107/S1600536813011501

Methyl 5′′-chloro-1′,1′′-dimethyl-2,2′′-dioxodispiro[indoline-3,2′-pyrrolidine-3′,3′′-indoline]-4′-carboxylate

Piskala Subburaman Kannan ^a, PanneerSelvam Yuvaraj ^b, Karthikeyan Manivannan ^b, Boreddy Siva Rami Reddy ^b, Arunachalathevar SubbiahPandi ^c,^*

PMCID: PMC3684914 PMID: 23795016

Abstract

In the title compound, C₂₂H₂₀ClN₃O₄, the central pyrrolidine ring adopts an envelope conformation on the N atom. The indolinone systems are individually roughly planar, with maximum deviations from their mean planes of 0.130 Å for the spiro C atom of the indolinone unit and 0.172 Å for the carbonyl C atom of the 5-chloro-1-methylindolinone unit. They make dihedral angles of 77.7 (8) and 86.1 (8)° with the mean plane through the central pyrrolidine ring. In the crystal, molecules are linked by N—H⋯O hydrogen bonds supported by C—H⋯O contacts into chains along the ab diagonal. The structure also features C—H⋯O hydrogen bonds, forming R ₂ ²(8) and R ₂ ²(16) rings and generating a three-dimensional array.

Related literature

For the biological activity of spiro-pyrrolidine derivatives, see: Obniska et al. (2003 ▶); Peddi et al. (2004 ▶); Kaminski & Obniska (2008 ▶); Stylianakis et al. (2003 ▶); Waldmann (1995 ▶). For the use of optically active pyrrolidines as intermediates, chiral ligands or auxiliaries in controlled asymmetric synthesis, see: Suzuki et al. (1994 ▶); Huryn et al. (1991 ▶). For related structures, see: Ganesh et al. (2012 ▶); Wei et al. (2011 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶) and for hydrogen-bond motifs see Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₂₂H₂₀ClN₃O₄
M _r = 425.86
Monoclinic,
a = 9.2543 (4) Å
b = 18.1387 (7) Å
c = 12.5147 (5) Å
β = 105.026 (2)°
V = 2028.90 (14) Å³
Z = 4
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 293 K
0.30 × 0.25 × 0.20 mm

Data collection

Bruker APEXII CCD area detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.936, T _max = 0.957
18586 measured reflections
5021 independent reflections
3789 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.125
S = 1.06
5021 reflections
278 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.21 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

Click here for additional data file.^{(29.7KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813011501/sj5312sup1.cif

e-69-0o825-sup1.cif^{(29.7KB, cif)}

Click here for additional data file.^{(245.9KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813011501/sj5312Isup2.hkl

e-69-0o825-Isup2.hkl^{(245.9KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯O1ⁱ	0.85 (2)	2.18 (2)	2.9112 (18)	143.3 (18)
C15—H15⋯O1ⁱ	0.93	2.46	3.156 (2)	132
C22—H22B⋯O3ⁱⁱ	0.96	2.56	3.324 (2)	137
C5—H5⋯O3ⁱⁱ	0.93	2.61	3.499 (2)	160
C9—H9⋯O3ⁱⁱⁱ	0.98	2.54	3.224 (2)	127

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

The authors thank the TBI X-ray facility, CAS in Crystallography and BioPhysics, University of Madras, Chennai, India, for the data collection.

supplementary crystallographic information

Comment

Spiro-pyrrolidine derivatives are unique tetracyclic 5-HT(2A) receptor antagonists (Obniska et al., 2003; Peddi et al., 2004). These derivatives possess anticonvulsant (Kaminski & Obniska, 2008) and anti-influenza virus (Stylianakis et al., 2003) activities. 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). Optically active pyrrolidines have also been used as intermediates, chiral ligands or auxiliaries in controlled asymmetric synthesis (Suzuki et al., 1994; Huryn et al., 1991).

X-Ray analysis confirms the molecular structure and atom connectivity as illustrated in Fig. 1. The geometries of the pyrrolidine and indole systems are comparable with those in related structures (Wei et al., 2011; Ganesh et al., 2012). The sum of the angles at N2 [336.9 (1)°] of the pyrrolidine rings is typical of sp³ hybridization. The indoline ring systems [N1/C1-C8 and N3/C12-C19] make dihedral angles of 77.7 (8) ° and 86.1(68° with respect to the mean plane of the central pyrrolidine ring system [N2/C7/C9/C10/C12]. This clearly shows that the indoline ring (N3/C12-C19) and the central pyrrolidine ring system are almost perpendicular to one another. The indole ring systems are essentially planar, with maximum deviations from the mean planes of 0.130 Å for the C12 and -0.172 Å for the C8 atoms, respectively.

The central pyrrolidine ring adopts an envelope conformation on the N2 atom, with puckering parameters q₂ = 0.419 (2) Å, φ = 1.555 (2)(Cremer & Pople, 1975 ). The pyrrolidine ring in the chloro-indole ring system adopts a twisted conformation on the C7 and C8 atoms, with puckering parameters of q₂ = 0.124 (2) Å, φ = 306.8 (7). The pyrrolidine ring in the indole ring system adopts an envelope conformation on the C12 atom, with puckering parameters q₂ = 0.113 (2) Å, φ = 251.6 (9).

In the crystal, six hydrogen bonds formed by each molecule. These include the formation of three inversion related contacts and atom O3 acting as a trifurcated acceptor. The molecules are stabilized by intermolecular C–H···O hydrogen bonds forming R²₂(8)rings from C9-H9···O3, contacts (Bernstein et al., 1995) while C5–H5···O3 contacts and C22-H22B···O3, H bonds generate R²₂(16) rings resulting in a three dimensional array Figure 2.

Experimental

A mixture of 1 equivalent of (E)-methyl 2-(5-chloro-1-methyl-2-oxoindolin-3-ylidene) acetate, 1 equivalent of isatin, 1H-indole-2,3-dione, and 1.5 equivalent of sarcosine, N-methylglycine were dissolved in acetonitrile. This reaction mixture was refluxed at 80°C for 8 hours. Progress of the reaction was monitored by thin layer chromatography. The product was dried and purified by column chromatography using ethyl acetate and hexane (1:9) as eluent to afford the title compound. (Yield = 90%). Single crystals suitable for X-ray diffraction were obtained by slow evaporation of a solution in ethyl acetate at room temperature.