(1′S)-4-(3,4-Dichlorophenyl)-1′-(3,5-dimethoxyphenyl)-1,2,3,4-tetrahydronaphthalene-2-spiro-2′-pyrrolizidine-3′-spiro-3′′-indoline-1,2′′-dione

E Theboral Sugi Kamala; R Murugan; S Nirmala; L Sudha; S Sriman Narayanan

doi:10.1107/S1600536808028614

. 2008 Sep 17;64(Pt 10):o1958–o1959. doi: 10.1107/S1600536808028614

(1′S)-4-(3,4-Dichlorophenyl)-1′-(3,5-dimethoxyphenyl)-1,2,3,4-tetrahydronaphthalene-2-spiro-2′-pyrrolizidine-3′-spiro-3′′-indoline-1,2′′-dione

E Theboral Sugi Kamala ^a, R Murugan ^b, S Nirmala ^a, L Sudha ^c,^*, S Sriman Narayanan ^b

PMCID: PMC2959408 PMID: 21201161

Abstract

In the title compound C₃₇H₃₂Cl₂N₂O₄, the unsubstituted pyrrolidine ring shows a twist conformation whereas the substituted pyrrolidine ring shows an envelope conformation. The dimethoxy benzene ring is perpendicular to the tetralone ring, making a dihedral angle of 89.94 (5)°. Molecules are linked into centrosymmetric dimers by N—H⋯O hydrogen bonds and the crystal structure is stabilized by C—H⋯π interactions and C—H⋯O hydrogen bonds. One methoxy group is disordered over two positions with the site occupancy factors of 0.84 (2) and 0.16 (2).

Related literature

For general background, see: Ma & Hecht (2004 ▶); Mitsuaki et al. (1997 ▶); Raghunathan & Suresh Babu (2006 ▶); Reddy & Rao (2006 ▶); Usui et al. (1998 ▶). For bond-length data, see: Allen et al. (1987 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). For asymmetry parameters, see: Nardelli (1983 ▶).

Experimental

Crystal data

C₃₇H₃₂Cl₂N₂O₄
M _r = 639.55
Triclinic,
a = 10.4475 (3) Å
b = 11.3047 (3) Å
c = 15.0170 (4) Å
α = 87.925 (2)°
β = 70.3220 (10)°
γ = 70.115 (2)°
V = 1564.29 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.25 mm⁻¹
T = 293 (2) K
0.40 × 0.20 × 0.20 mm

Data collection

Bruker Kappa APEXII diffractometer
Absorption correction: multi-scan (Blessing, 1995 ▶) T _min = 0.852, T _max = 0.943
41544 measured reflections
10800 independent reflections
7229 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.056
wR(F ²) = 0.191
S = 1.04
10800 reflections
414 parameters
3 restraints
H-atom parameters constrained
Δρ_max = 0.79 e Å⁻³
Δρ_min = −0.44 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: APEX2 and SAINT (Bruker, 2004 ▶); data reduction: SAINT and XPREP (Bruker, 2004 ▶); program(s) used to solve structure: SHELXS86 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808028614/bt2783sup1.cif

e-64-o1958-sup1.cif^{(31.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808028614/bt2783Isup2.hkl

e-64-o1958-Isup2.hkl^{(517.4KB, 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
N2—H2⋯O1ⁱ	0.86	2.01	2.8566 (16)	166
C37—H37C⋯Cg1ⁱⁱ	0.93	2.75	3.493 (2)	134
C4—H4⋯O1	0.98	2.56	3.0989 (16)	114
C5—H5⋯O2	0.98	2.27	2.790 (2)	112
C13—H13⋯O2	0.93	2.57	3.129 (2)	119
C23—H23A⋯O1	0.97	2.35	3.015 (2)	125
C22—H22⋯N2	0.98	2.55	3.447 (2)	152

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Symmetry codes: (i) Inline graphic ; (ii) . Cg1 is the centroid of the C30–C35 ring.

Acknowledgments

ETSK thanks Professor M. N. Ponnuswamy and Professor D. Velmurugan, Department of Crystallography and Biophysics, University of Madras, India, for their guidance and valuable suggestions. ETSK also thanks SRM Management for their support.

supplementary crystallographic information

Comment

Spiro compounds represent an important class of naturally occurring substances exhibiting significant biological properties. The spirooxindole system is the core structure of many pharmacological agents and natural alkaloids (Ma & Hecht, 2004). Spirotryprostatin A, a natural alkaloid isolated from the fermentation broth of Aspergillus fumigatus, has been identified as a novel inhibitor of microtubule assembly (Usui et al., 1998). Because of their synthetic and biological potential, considerable interest has been focused on the synthesis of spirooxindole derivatives via 1,3-dipolar cycloaddition reactions (Raghunathan & Suresh Babu, 2006). Chiral polyhydroxy alkaloids show remarkable biological properties. Among these, pyrrolidine alkaloids carrying an aromatic substituent on the ring are of a rare class found in nature (Reddy & Rao, 2006).They are useful in preventing and treating rheumatoid arthritis, asthma, allergies, rhinitis and related diseases (Mitsuaki et al., 1997).

Fig 1 shows the ORTEP (Farrugia, 1997) plot of the title compound. Bond lengths and angles are comparable with other reported values (Allen et al.,1987).

In the molecule the pyrrolidine ring N1/C4—C7 and the tetralone ring C6/C15/C16/C21/C22/C23 exhibit envelope conformations with the asymmetry parameters (Nardelli, 1983) ΔC_s(C4)/C(16) = 5.20 (14)/2.64 (15) and with the puckering parameters (Cremer & Pople, 1975) q2 = 0.3779 (16) Å and 0.4787 (17)Å and φ2 =212.1 (2)° / 124.3 (3)°. The pyrrolidine ring N1/C1—C4 exhibits a twist conformation with assymetry parameter ΔC_s (N1) =16.01 (18), ΔC₂ (C1) =62.94 (18) and with the puckering parameters q2 = 0.3901 (18) Å, φ2 = 18.9 (3)°.

The sum of bond angles around N1 [329.84°] and that around atom N2 [360.00°] indicate sp³ and sp² hybridizations. The dimethoxy benzene ring C30—C35 is perpendicular to the tetralone ring C6/C15/C16/C21/C22/C23 and the phenyl ring C16—C21 making a dihedral angle of 89.94 (5)° and 89.98 (6)° respectively. The phenyl and the tetralone rings are almost coplanar with each other making a dihedral angle of 6.53 (5)°.

In the crystal packing, atoms O1 and N2 are involved in intermolecular N—H···O interactions and atoms O1 and O2 are involved in intramolecular C-H···O interactions. The molecules pack into distinct layers facilitated by C-H···π interactions.

Experimental

1.0 mol of (2E)-4-(3,4-dichlorophenyl)-2-(3,5-dimethoxybenzylidene)-3, 4-dihydronaphthalen-1(2H)-one (1.0 g), 1.0 mol of isatin (0.33 g) and 1.0 mol of L-proline were refluxed in methanol at 65°C for about 5.0 hrs with constant stirring to afford the cycloadduct. The reaction mixture was monitored by TLC. After the completion of reaction, the reaction mixture was allowed to cool. The solvent was removed by vacuum, the crude solid was purified by column chromatography using n-hexane: ethylacetate (8:2). The cycloadduct was recrystallized by chloroform: methanol (9:1).