5-Chloro-5′′-(4-chloro­benzyl­idene)-4′-(4-chloro­phen­yl)-1′,1′′-dimethyldi­spiro­[indoline-3,2′-pyrrolidine-3′,3′′-piperidine]-2,4′′-dione

I S Ahmed Farag; Adel S Girgis; A A Ramadan; A M Moustafa; Ahmed F Mabied

doi:10.1107/S1600536814004309

. 2014 Feb 28;70(Pt 3):o379–o380. doi: 10.1107/S1600536814004309

5-Chloro-5′′-(4-chlorobenzylidene)-4′-(4-chlorophenyl)-1′,1′′-dimethyldispiro[indoline-3,2′-pyrrolidine-3′,3′′-piperidine]-2,4′′-dione

I S Ahmed Farag ^a,^‡, Adel S Girgis ^b, A A Ramadan ^c, A M Moustafa ^a, Ahmed F Mabied ^a,^*

PMCID: PMC3998502 PMID: 24765059

Abstract

The racemic title compound, C₃₀H₂₆Cl₃N₃O₂, comprises two spiro links, the first connecting the piperidine and pyrrolidine rings and the other connecting the indole and pyrrolidine rings. The piperidine ring adopts a half-chair conformation, while the pyrrolidine ring has an envelope conformation with the unsubstituted C atom as the flap. The dihedral angles between the two p-Cl-substituted benzene rings and the indole ring are 33.13 (14) and 54.11 (14)°. In the crystal, molecules form inversion dimers through pairs of N—H⋯O hydrogen bonds [graph set R ₂ ²(8)]. Aromatic C—H⋯O hydrogen bonds extend these dimers into a ribbon structure, enclosing R ² ₂(14) ring motifs, along the a-axis direction.

Related literature

For the biological activity of related dispiro-oxindole analogues, see: Girgis et al. (2009a ▶,b ▶, 2012 ▶); George et al. (2013 ▶). For related structural studies, see: Farag et al. (2014a ▶,b ▶,c ▶); Moustafa et al. (2012 ▶). For the synthesis of the precursor molecule, see: Modzelewska et al. (2006 ▶). For graph-set analysis, see: Etter et al. (1990 ▶). For details of the weighting scheme used, see: Watkin et al. (1994 ▶). H atoms were refined with riding constraints (Cooper et al., 2010 ▶).

Experimental

Crystal data

C₃₀H₂₆Cl₃N₃O₂
M _r = 566.91
Triclinic,
a = 11.2102 (3) Å
b = 11.5909 (3) Å
c = 12.3569 (4) Å
α = 99.0734 (8)°
β = 90.1887 (9)°
γ = 116.4041 (10)°
V = 1415.22 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.36 mm⁻¹
T = 298 K
0.35 × 0.19 × 0.10 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: multi-scan [Görbitz (1999 ▶) and DENZO/SCALEPACK (Otwinowski & Minor, 1997 ▶)] T _min = 0.630, T _max = 0.876
16419 measured reflections
6508 independent reflections
3663 reflections with I > 2σ(I)
R _int = 0.076

Refinement

R[F ² > 2σ(F ²)] = 0.057
wR(F ²) = 0.111
S = 1.01
3663 reflections
344 parameters
H-atom parameters constrained
Δρ_max = 0.55 e Å⁻³
Δρ_min = −0.54 e Å⁻³

Data collection: COLLECT (Nonius, 2001 ▶).; cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SUPERFLIP (Palatinus & Chapuis, 2007 ▶); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ▶); molecular graphics: CAMERON (Watkin et al., 1996 ▶) and DIAMOND (Brandenburg, 2012 ▶); software used to prepare material for publication: CRYSTALS; software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) New_Global_Publ_Block, I. DOI: 10.1107/S1600536814004309/zs2286sup1.cif

e-70-0o379-sup1.cif^{(23.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814004309/zs2286Isup2.hkl

e-70-0o379-Isup2.hkl^{(404.8KB, hkl)}

CCDC reference: 988672

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
C6—H61⋯O19ⁱ	0.96	2.47	3.168 (5)	130
N30—H301⋯O29ⁱⁱ	0.96	1.90	2.844 (5)	167

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

Acknowledgments

This study was supported financially by the Science and Technology Development Fund (STDF), Egypt (grant No. 1133).

supplementary crystallographic information

1. Introduction

Spiropyrrolidinyl-oxindole represents the main alkaloid skeleton of naturally occurring substances characterized by promising biological and/or pharmacological properties. In continuation of our research program directed towards synthesis of biologically active compounds possessing this motif (Farag et al., 2014a-c; George et al., 2013; Girgis et al., 2012, 2009a,b; Moustafa et al., 2012), a novel analog, C₃₀H₂₆Cl₃N₃O₂, is described in the present study utilizing a facile regio- as well as stereoselective procedure.

2. Experimental

2.1. Synthesis and crystallization

A mixture of equimolar amounts of 3E,5E-3,5-bis(4-chlorophenylmethylidene)-1-methyl-4-piperidone (5 mmol) [prepared by a literature procedure (Modzelewska et al., 2006)], 5-chloroisatin and sarcosine in absolute ethanol (25 ml) was heated under reflux for 9 h (TLC monitoring). The separated solid was collected and recrystallized from n-butanol affording the title compound, 5-chloro-5''-(4-chlorobenzylidene)-4'-(4-chlorophenyl)-1',1''-dimethyldispiro[indoline-3,2'-pyrrolidine-3',3''-piperidine]-2,4''-dione, as pale-yellow crystals. M.p. 237-239 °C; Yield 81%; Anal. Calcd. for C₃₀H₂₆Cl₃N₃O₂ (566.92): C, 63.56; H, 4.62; N, 7.41. Found: C, 63.69; H, 4.71; N, 7.48. IR: ν_max/cm^-1 3164 (NH), 1690 (C═O), 1594, 1483 (C═C).

2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. The relatively large ratio of minimum to maximum corrections applied in the multiscan process reflect changes in the illuminated volume of the crystal. Changes in illuminated volume were kept to a minimum, and were taken into account (Görbitz, 1999) by the multi-scan inter-frame scaling [DENZO/SCALEPACK (Otwinowski & Minor, 1997)]. The H atoms were all located in a difference map, but those attached to carbon atoms were repositioned geometrically and initially refined with soft restraints on the bond lengths and angles to regularise their geometry (C—H in the range 0.93–0.98, N—H in the range 0.86–0.89, N—H to 0.86 and O—H = 0.82 Å) and U>_iso(H) (in the range 1.2–1.5 times U_eq of the parent atom), after which the positions were refined with riding constraints (Cooper et al., 2010).

3. (Results and Discussion)

In the racemic title molecule (Fig. 1), two spiro links exist, one in which the piperidine and pyrrolidine rings are connected at C12, the other with the pyrrolidine ring and indole residue connected at C11. The piperidine ring adopts a half-chair conformation where the C13 atom lies 0.75 (2) Å out of the mean plane of the remaining five atoms (C12–N14) with maximum deviation 0.086 (2) at C16. The pyrrolidine ring has an envelope conformation with the flap atom being C9 which lies 0.608 (3) Å out of the mean plane of the remaining four atoms (C8–N10), in which the maximum deviation [0.088 (3)] is at C11. The two 4-chloro-substituted benzene rings defined by (C2–C7) and (C21–C27) make dihedral angles of 33.1 (14) and 54.11 (14)°, respectively, with the indole ring. In the crystal, the molecules form centrosymmetric cyclic dimers through duplex intermolecular N30—H···O29ⁱ hydrogen bonds (Table 1) [graph set R²₂(8) (Etter et al., 1990)]. Centrosymmetric duplex aromatic C6—H···O19ⁱⁱ hydrogen-bonding associations [graph set R²₂(14)] extend these dimers into a one-dimensional ribbon structure extending along a (Fig. 2) (for symmetry codes, see Table 1). Also present in the molecule is an intramolecular C38—H···π interaction with the ring centroid (Cg) of the five-membered C28–N30 ring.