Ethyl 1-benzyl-1,2,3,3a,4,10b-hexa­hydro­pyrrolo­[2′,3′:3,4]pyrrolo­[1,2-a]benzimidazole-2-carboxyl­ate

Liping Meng; James C Fettinger; Mark J Kurth

doi:10.1107/S1600536811014292

. 2011 Apr 29;67(Pt 5):o1214. doi: 10.1107/S1600536811014292

Ethyl 1-benzyl-1,2,3,3a,4,10b-hexahydropyrrolo[2′,3′:3,4]pyrrolo[1,2-a]benzimidazole-2-carboxylate

Liping Meng ^a, James C Fettinger ^a, Mark J Kurth ^a,^*

PMCID: PMC3089295 PMID: 21754512

Abstract

The title molecule, C₂₂H₂₃N₃O₂, was obtained via an intramolecular cycloaddition of an azomethine ylide and an alkene tethered by a benzimidazole unit. The benzoimidazole unit is essentially planar, with an r.m.s. deviation of 0.0087 Å from the nine constituent atoms. It has a cis fusion of the two pyrrolidine rings as well as a cis ester appendage. The two pyrrolidine rings rings have envelope conformations. The crystal packing is stabilized by aromatic π–π stacking of parallel benzimidazole ring systems, with a centroid-to-centroid distance of 3.518 (6) Å. Weak intermolecular C—H⋯O contacts may also play a role in the stability of the packing.

Related literature

Polycyclic nitrogen-containing heterocycles form the basic skeleton of numerous alkaloids and physiologically active compounds, see: Southon & Buckingham (1989 ▶). Conformational studies have been reported for related pyrrolidino[3,4-b]pyrrolidine-2-carboxylates obtained from intramolecular cycloaddition of azomethine ylides, see: Cheng et al. (2001 ▶); Meng et al. (2007 ▶). For related literature on the pharmaceutical properties of benzimidazole and pyrrolidine, see: Gudmundsson et al. (2000 ▶); Hamilton & Steiner (1997 ▶). For related literature on the azomethine ylide cycloaddition in similar systems, Pedrosa et al. (2006 ▶); Yang et al. (2006 ▶).

Experimental

Crystal data

C₂₂H₂₃N₃O₂
M _r = 361.43
Monoclinic,
a = 9.2498 (5) Å
b = 13.8999 (7) Å
c = 14.2258 (7) Å
β = 90.345 (1)°
V = 1829.00 (16) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 90 K
0.39 × 0.16 × 0.13 mm

Data collection

Bruker SMART1000 CCD area-detector diffractometer
Absorption correction: numerical (SADABS; Blessing, 1995 ▶; Sheldrick, 2007 ▶) T _min = 0.962, T _max = 0.989
16147 measured reflections
4194 independent reflections
3080 reflections with I > 2σ(I)
R _int = 0.037

Refinement

R[F ² > 2σ(F ²)] = 0.037
wR(F ²) = 0.095
S = 1.09
4194 reflections
336 parameters
All H-atom parameters refined
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Data collection: SMART (Bruker, 2002 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP in SHELXTL/PC (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811014292/wn2427sup1.cif

e-67-o1214-sup1.cif^{(21.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811014292/wn2427Isup2.hkl

e-67-o1214-Isup2.hkl^{(205.7KB, 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
C11—H11B⋯O12ⁱ	1.005 (15)	2.399 (15)	3.3344 (17)	154.5 (12)
C18—H18⋯O12ⁱⁱ	0.968 (15)	2.514 (16)	3.3505 (17)	144.6 (12)

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

Acknowledgments

The authors thank the National Science Foundation (grant No. CHE-0910870) and the National Institutes of Health (grant No. GM0891583) for financial support of this work.

supplementary crystallographic information

Comment

Polycyclic nitrogen-containing heterocycles form the basic skeleton of numerous alkaloids and physiologically active compounds (Southon & Buckingham, 1989). The title polycyclic N-heterocycle, ethyl 1-benzylpyrrolidino[2',3':3,4]pyrrolidino[1,2-a] benzimidazole-2-carboxylate, was obtained via an intramolecular azomethine ylide cycloaddition and possesses two medicinally relevant pharmacophores – benzimidazole and pyrrolidine (Gudmundsson et al., 2000; Hamilton & Steiner, 1997)– in one rigid molecule; the title compound may afford important bioactivity.

In the structure of the title compound (Fig. 1), the benzoimidazole unit is essentially planar, with a root mean square deviation of 0.0087 Å from the nine constituent atoms. The two pyrrolidine rings have envelope forms and are cis fused, which is consistent with conventional azomethine ylide cycloadditions in similar systems (Pedrosa et al., 2006; Yang et al., 2006). However, unlike the previously reported analogues obtained from an intramolecular azomethine ylide and alkene cycloaddition tethered by an oxazolidin-2-one (Cheng et al., 2001), the ester appendage in the title structure was unambiguously assigned as cis to the angular protons H2A and H10A by X-ray crystallography. The crystal packing (Fig. 2) exhibits π–π stacking of parallel benzimidazole ring systems, with a Cg1···Cg2 distance of 3.518 Å [Cg1 and Cg2 are the centroids of the C3A–C8A benzene ring in one molecule and the C2B/N2/C3A/C8A/N8 imidazole ring in the other molecule, respectively]. Intermolecular C—H···O contacts may also play a role in the stability of the packing.

Experimental

The title compound was prepared from 1-allyl-1H-benzimidazole-2-carbaldehyde, N-benzylglycine ethyl ester hydrochloride, and triethylamine according to the procedure reported by Meng et al. (2007). Colourless blocks of the title compound were obtained by recrystallization from EtOAc/n-hexane 1:1 with slow evaporation at room temperature. These crystals were suitable for X-ray crystallography.