(3RS,4SR)-Methyl 4-(2-chloro-5,8-di­methoxy­quinolin-3-yl)-1-phenyl­pyrrolidine-3-carboxyl­ate

Saida Benzerka; Abdelmalek Bouraiou; Sofiane Bouacida; Salah Rhouati; Ali Belfaitah

doi:10.1107/S1600536808031838

. 2008 Oct 9;64(Pt 11):o2089–o2090. doi: 10.1107/S1600536808031838

(3RS,4SR)-Methyl 4-(2-chloro-5,8-dimethoxyquinolin-3-yl)-1-phenylpyrrolidine-3-carboxylate

Saida Benzerka ^a, Abdelmalek Bouraiou ^a, Sofiane Bouacida ^b,^*,^‡, Salah Rhouati ^a, Ali Belfaitah ^a

PMCID: PMC2959501 PMID: 21580954

Abstract

The molecule of the title compound, C₂₃H₂₃ClN₂O₄, contains a quinolyl unit linked to a functionalized pyrrolidine system with a 3,4-trans arrangement of the substituents. The unit cell contains two stereoisomers that have the absolute stereochemistry 3S,4R and 3R,4S. The pyrrolidine ring adopts a twist conformation with pseudo-rotation parameters P = 258.2 (3)° and τ(M) = 35.3 (1)°. The packing is stabilized by C—H⋯π interactions and offset π–π stacking (centroid-to-centroid distance = 3.849 Å, interplanar distance = 3.293 Å and slippage = 1.994 Å) between phenyl rings, leading to a two-dimensional network.

Related literature

For general background, see: Padwa et al. (1999 ▶); Sahu et al. (2002 ▶); Robert & Meunier (1998 ▶); Dow et al. (2006 ▶); Witherup et al. (1995 ▶); Kravchenko et al. (2005 ▶); Bouraiou et al. (2008 ▶); Rezig et al. (2000 ▶); Moussaoui et al. (2002 ▶); Menasra et al. (2005 ▶); Rao et al. (1981 ▶). For related structures, see: Belfaitah et al. (2006 ▶); Bouraiou et al. (2007a ▶,b ▶).

Experimental

Crystal data

C₂₃H₂₃ClN₂O₄
M _r = 426.88
Monoclinic,
a = 9.579 (1) Å
b = 17.518 (1) Å
c = 12.944 (2) Å
β = 109.01 (2)°
V = 2053.6 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 296 (2) K
0.15 × 0.06 × 0.05 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: none
9271 measured reflections
4717 independent reflections
3062 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.055
wR(F ²) = 0.178
S = 1.03
4717 reflections
274 parameters
H-atom parameters constrained
Δρ_max = 0.38 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Data collection: COLLECT (Nonius, 1998 ▶); cell refinement: SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: DENZO (Otwinowski & Minor, 1997 ▶) and SCALEPACK; program(s) used to solve structure: SIR2002 (Burla et al., 2003 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 ▶), ORTEP-3 for Windows (Farrugia, 1997 ▶) and CAMERON (Pearce et al., 2000 ▶); software used to prepare material for publication: PLATON (Spek, 2003 ▶) and WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808031838/dn2384sup1.cif

e-64-o2089-sup1.cif^{(20.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808031838/dn2384Isup2.hkl

e-64-o2089-Isup2.hkl^{(226.4KB, hkl)}

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

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

Cg1 is the centroid of the C17–C22 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C12—H12B⋯Cg1ⁱ	0.96	2.67	3.601 (3)	164

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Symmetry code: (i) Inline graphic .

Acknowledgments

We are grateful to Professor Lahcéne Ouahab (Organométalliques et Materiaux Moléculaire, Université de Rennes I, France) for data collection facilities and Professor Abdelmadjid Debache (PHYSYNOR, Université Mentouri, Constantine, Algeria) for his assistance. Thanks are due to MESRS (Ministére de l’Enseignement Supérieur et de la Recherche Scientifique) for financial support.

supplementary crystallographic information

Comment

Quinolines derivatives have attracted considerable interest for many years due to their presence in the skeleton of a large number of bioactive compounds and natural products (Padwa et al., 1999; Sahu et al. 2002). For example, quinoline alkaloids, such as quinine, chloroquin, mefloquine and amodiaquine, are used as efficient drugs for the treatment of malaria (Robert & Meunier, 1998; Dow et al., 2006). On the other hand, pyrrolidine containing compounds are also of significant importance because of their biological activities and widespread employment in catalysis (Witherup et al., 1995; Kravchenko et al., 2005). As a part of our program related to the preparation and biological evaluation of quinolyl derivatives (Belfaitah et al., 2006; Bouraiou et al., 2008, 2007a,b; Rezig et al., 2000; Moussaoui et al., 2002), we have previously reported the preparation of some 3-pyrrolylquinoline derivatives via an 1,3-dipolar cycloaddition/oxydation key sequence from quinolinyl α,β-unsaturated esters as starting materials (Menasra et al., 2005). In a continuation of our efforts in this area, we report here the crystal structure of new N-phenylpyrrolidine derivative bearing a quinoline ring at C-3 and ester group at C-4 via an 1,3-dipolar cycloaddition reaction.

The asymmetric unit of title compound contains a quinolyl unit linked to a functionalized pyrrolidine system with a 3,4-trans arrangement of the substituents (Fig. 1). The two rings of quinolyl moiety are fused in an axial fashion and form a dihedral angle of 0.67 (6)° and this quasi plane system forms dihedral angles of 83.76 (7)° with the phenyl ring.The pyrrolidine was obtained with conservation of the stereochemistry of starting alkene, giving only one diastereoisomer with no evidence of any other isomers in the ¹H NMR spectra or thin-layer chromatography of the crude product. X-ray crystallography of (I) showed an asymmetric unit which contains only one stereoisomer and the analysis of the unit cell demonstrate that the second stereoisomer is generated via a symmetry element. The two stereoisomers have for each one, the absolute stereochemistry 3S,4R and 3R,4S of the new stereocenters created in the cycloaddition reactions.

The pyrrolidine ring adopts twist conformation on C13—C14 with pseudorotation parameters P = 258.2 (3)° and τ(M) = 35.3 (1)° (Rao et al., 1981), the C13 atom deviates by 0.213 (2)Å from the mean plane through the remaining atoms.

The packing is stabilized by C—H···π interaction involving the C17—C22 phenyl ring (Table 1). Offset π···π stacking between this phenyl ring and the symmetry (-x, -y, -z) related ring might also be considered with a centroid-to-centroid distance of 3.849 Å, an interplanar distance of 3.293Å and a slippage of 1.994Å (Spek, 2003). These weak interactions build up a two dimensional network (Fig. 2).

Experimental

The title compound I was synthesized by refluxing 1.0 mmol of (E)-methyl 3-(2-chloro-5,8-dimethoxyquinolin-3-yl) acrylate, 2.0 mmol of N-phenylglycine, and 5.0 mmol of CH₂O in dry toluene (5.10^-3M). The contents were then cooled and filtered off and the filtrate was concentrated under reduced pressure. The residue was subjected to column chromatography (silica gel, eluent: CH₂Cl₂) to afford pure product. Crystals suitable for X-ray analysis were obtained by slow evaporation of a dichloromethane solution of (I).