1-Benzyl-4′,5′-diphenyl­piperidine-3-spiro-3′-pyrrolidine-2′-spiro-3′′-indoline-4,2′′-dione

J Suresh; R Suresh Kumar; A Rajapriya; S Perumal; P L Nilantha Lakshman

doi:10.1107/S160053680804141X

. 2008 Dec 17;65(Pt 1):o147–o148. doi: 10.1107/S160053680804141X

1-Benzyl-4′,5′-diphenylpiperidine-3-spiro-3′-pyrrolidine-2′-spiro-3′′-indoline-4,2′′-dione

J Suresh ^a, R Suresh Kumar ^b, A Rajapriya ^a, S Perumal ^b, P L Nilantha Lakshman ^c,^*

PMCID: PMC2968062 PMID: 21581605

Abstract

The asymmetric unit of the title compound, C₃₄H₃₁N₃O₂, consists of two independent molecules which differ slightly in the orientations of the phenyl rings with respect to the pyrrolidine ring. In both molecules, the piperidin-4-one ring adopts a chair conformation, whereas the pyrrolidine ring adopts an envelope conformation in one of the molecules and a twisted conformation in the other. An intramolecular C—H⋯O hydrogen bond is observed. The crystal packing is stabilized by intermolecular N—H⋯O hydrogen bonds and C—H⋯π interactions.

Related literature

For the biological activities of oxindole derivatives, see: Bhattacharya et al. (1982 ▶); Glover et al. (1998 ▶); Govind et al. (2004 ▶); Hilton et al. (2000 ▶); Jeyabharathi et al. (2001 ▶); Kirsch et al. (2004 ▶); Klumpp et al. (1998 ▶); Kumar et al. (1993 ▶, 2006 ▶); Medvedev et al. (1996 ▶). For bond-length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₃₄H₃₁N₃O₂
M _r = 513.62
Triclinic,
a = 10.8575 (3) Å
b = 13.7909 (5) Å
c = 20.5053 (9) Å
α = 89.767 (6)°
β = 75.056 (4)°
γ = 71.846 (3)°
V = 2809.1 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 293 (2) K
0.17 × 0.13 × 0.11 mm

Data collection

Nonius MACH-3 diffractometer
Absorption correction: ψ scan (North et al., 1968 ▶) T _min = 0.988, T _max = 0.992
11592 measured reflections
9879 independent reflections
4342 reflections with I > 2σ(I)
R _int = 0.026
2 standard reflections frequency: 60 min intensity decay: none

Refinement

R[F ² > 2σ(F ²)] = 0.053
wR(F ²) = 0.157
S = 0.99
9879 reflections
711 parameters
2 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.28 e Å⁻³

Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1994 ▶); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1996 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2003 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680804141X/ci2737sup1.cif

e-65-0o147-sup1.cif^{(43.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053680804141X/ci2737Isup2.hkl

e-65-0o147-Isup2.hkl^{(473.4KB, 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⋯O4	0.86	2.03	2.881 (3)	169
N6—H6⋯O2	0.86	2.05	2.896 (3)	170
C40—H40A⋯O4	0.97	2.35	2.925 (4)	118
C12—H12⋯Cg1ⁱ	0.93	2.80	3.586 (6)	144

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Symmetry code: (i) Inline graphic . Cg1 is the centroid of the C29–C34 ring.

Acknowledgments

SP thanks the CSIR for funding a major research project.

supplementary crystallographic information

Comment

The development of new efficient methods to synthesize N-heterocycles with structural diversity is one of the major interests of modern synthetic organic chemists (Kirsch et al., 2004). Oxindole derivatives are known to possess a variety of biological activities (Klumpp et al., 1998) such as (i) a potent inhibitor of monoamine oxidase (MAO) in human urine and rat tissues (Glover et al., 1998) (ii) inhibition of several enzymes such as acetylcholinestrease (AChE) (Kumar et al., 1993) and atrial natriuretic peptide-stimulated guanylate cyclase and (iii) a potent antagonist of in vitro receptor binding by atrial natriuretic peptide (Medvedev et al., 1996) besides possessing a wide range of central nervous system activities (Bhattacharya et al., 1982). The derivatives of spirooxindole ring systems are used as antimicrobial, antitumour 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). Our interest in preparing pharmacologically active pyrrolidines led us to the title compound, and we have undertaken X-ray crystal structure determination of these compounds in order to establish their conformations.

The asymmetric unit of the title compound contains two independent molecules, and these pair has almost identical geometry (Fig. 1 and Fig. 2). In both the molecules, the bond lengths and bond angles show normal values and agree with each other (Allen et al., 1987). The sums of the angles at atoms N2 and N5 of the pyrrolidine rings 342.3 and 333.4°, respectively, are in accordance with sp³-hybridization, and sums of the angles at atoms N3 and N6 of the indolin-2-one moiety 360 and 359.8° confirms the sp²-hybridization (Govind et al., 2004; Kumar et al., 2006; Jeyabharathi et al., 2001). The bond lengths within the indolin-2-one moiety match with those in similar structures (Kumar et al., 2006; Jeyabharathi et al., 2001).

In one of the independent molecules the pyrrolidine ring (in ring N5/C55/C48/C39/C62, C55 is the flap atom) adopts an envelope conformation and in the other it exhibits a twisted conformation. In the indolin-2-one ring systems, the benzene and pyrrole rings are individually planar and make dihedral angles of 3.8 (2) and 1.7 (2)°, while atoms O2 and O4 deviate from the pyrrole ring of the indolin-2-one system by -0.224 (5) and 0.117 (5) Å, respectively, because of the different interactions in which these O atoms are involved (Table 1). The orientations of the phenyl groups with respect to the pyrrolidine ring differ slightly in the two independent molecules.

N—H···O hydrogen bonds between the two molecules in the asymmetric unit generate an R₂²(8) graph set motif (Table 1 and Fig. 3). In addition, a C—H···π interaction (Table 1) is also found.

Experimental

A mixture of 1-benzyl-4-piperidinone (0.2 g, 0.001 mol), isatin (0.156 g, 0.001 mol) and phenylglycine (0.320 g, 0.002 mol) in methanol-water (2:1, 30 ml) were refluxed in a water bath for 24 h. After completion of the reaction as monitored by TLC, the excess solvent was removed under vacuum and the residue subjected to flash column chromatography using petroleum ether-ethyl acetate mixture (8:2 v/v) as eluent (yield: 0.220 g, 41%; m.p. 464–465 K)