Methyl 4-(4-methoxy­phen­yl)-1,2,3,3a,4,4a,5,12c-octa­hydro­benzo[f]chromeno[3,4-b]pyrrolizine-4a-carboxyl­ate

S Nirmala; E Theboral Sugi Kamala; L Sudha; S Kathiravan; R Raghunathan

doi:10.1107/S1600536809027639

. 2009 Jul 22;65(Pt 8):o1938. doi: 10.1107/S1600536809027639

Methyl 4-(4-methoxyphenyl)-1,2,3,3a,4,4a,5,12c-octahydrobenzo[f]chromeno[3,4-b]pyrrolizine-4a-carboxylate

S Nirmala ^a, E Theboral Sugi Kamala ^a, L Sudha ^b,^*, S Kathiravan ^c, R Raghunathan ^c

PMCID: PMC2977484 PMID: 21583620

Abstract

In the title compound, C₂₇H₂₇NO₄, both the pyrrolidine rings in the pyrrolizine ring system adopt envelope conformations, whereas the dihydropyran ring adopts a half-chair conformation. The methoxyphenyl group is oriented at an angle of 53.72 (4)° with respect to the naphthalene ring system. Intramolecular C—H⋯O hydrogen bonds are observed. The crystal structure is stabilized by weak intermolecular C—H⋯π interactions.

Related literature

For the biological activity of pyrrolizine derivatives, see: Amal Raj et al. (2003 ▶); Atal (1978 ▶); Denny (2001 ▶); Suzuki et al. (1994 ▶). For a related structure, see: Ramesh et al. (2007 ▶). For ring-puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₂₇H₂₇NO₄
M _r = 429.50
Triclinic,
a = 8.7484 (4) Å
b = 11.4284 (5) Å
c = 11.4444 (6) Å
α = 104.127 (2)°
β = 91.824 (3)°
γ = 101.555 (2)°
V = 1083.19 (9) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.30 × 0.25 × 0.20 mm

Data collection

Bruker Kappa APEXII area-detector diffractometer
Absorption correction: multi-scan (Blessing, 1995 ▶) T _min = 0.974, T _max = 0.983
22194 measured reflections
4310 independent reflections
2976 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.046
wR(F ²) = 0.131
S = 1.03
4310 reflections
289 parameters
H-atom parameters constrained
Δρ_max = 0.35 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809027639/bt5001sup1.cif

e-65-o1938-sup1.cif^{(24.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809027639/bt5001Isup2.hkl

e-65-o1938-Isup2.hkl^{(206.9KB, 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
C1—H1⋯O2	0.98	2.32	2.792 (2)	108
C23—H23⋯Cg1ⁱ	0.93	2.92	3.633 (3)	135
C25—H25C⋯Cg2ⁱⁱ	0.96	2.90	3.715 (3)	143

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Symmetry codes: (i) Inline graphic ; (ii) . Cg1 is the centroid of the C3–C8 ring and Cg2 is the centroid of the C19–C24 ring.

Acknowledgments

SN thanks Dr Babu Vargheese, SAIF, IIT Madras, India, for his help with the data collection. SN thanks SRM management, India, for their support.

supplementary crystallographic information

Comment

Pyrrolizidine alkaloids occur in more than 40 genera, and are responsible for heavy losses of livestock and poisoning in man due to their hepatotoxity. These alkaloids are also reported to possess a number of other biological activities (Atal, 1978) and are used as DNA minor groove alkylating agents (Denny, 2001). Substituted pyrrolidines have gained much importance because they are the structural elements of many alkaloids. It has been found that they exhibit antifungal activity against various pathogens (Amal Raj et al., 2003). Optically active pyrrolidine derivatives have been used as intermediates in controlled asymmetric synthesis (Suzuki et al., 1994). In view of its biological importance, the crystal structure determination of the title compound was undertaken.

A displacement ellipsoid plot of the title compound is shown in Fig. 1. The pyrrolizine ring system is folded about the bridging N1—C15 bond, as observed in related structures (Ramesh et al., 2007). The sum of bond angles around atom N1 [337.9 (7)°] is in accordance with sp³ hybridization. The napthalene ring system C2-C11 and the methoxyphenyl group C19—C25/O4 are oriented at an angle of 53.72 (4)° with respect to each other. The methoxy group is almost coplanar with the C19—C24 benzene ring [C25—O4—C22—C23 = -174.4 (2)°]. The heterocyclic ring O1/C1/C2/C11—C13 of the chromenopyrrolizine unit adopt a half chair conformation with puckering parameters q₂= 0.381 (2) Å, q₃= -0.281 (2) Å and φ= -91.3 (3)° (Cremer and Pople, 1975). In the pyrrolizine ring system, both the pyrrolidine rings, N1/C1/C13—C15 and N1/C15—C18 adopt envelope conformation with puckering parameters q₂= 0.352 (2) Å, φ= 78.4 (3)° and q₂ = 0.402 (3) Å, φ= 100.9 (3)° (Cremer and Pople, 1975) respectively. In the ring N1/C1/C13—C15, atom C13 deviates by 0.547 (8) Å from the least-square plane through the remaining four atoms, whereas in the ring N1/C15—C18, atom C17 deviates by -0.616 (4) Å from the least-squares plane through the remaining four atoms.

The crystal packing is stabilized by intramolecular C—H···O and weak intermolecular C—H···π (C23—H23···Cg1; Cg1 is the centroid of the C3—C8 ring and C25—H25C···Cg2; Cg2 is the centroid of the C19—C24 ring) interactions (Table 1).

Experimental

A mixture of (Z)-methyl-2-((1-formylnaphthalen-2-yloxy)methyl)-3-(4-methoxyphenyl) acrylate (20 mmol) and proline (30 mmol) were refluxed in benzene for 20 h and the solvent was removed under reduced pressure. The crude product was subjected to column chromatography to get the pure product. A chloroform and methanol (1:1) solvent mixture was used for the crystallization using the slow evaporation method.