{2-[(Benzo­yloxy)meth­yl]-1-oxo-3H-pyrrolizin-2-yl}methyl benzoate

Yousaf Ali; Sammer Yousuf; Nighat Afza; Yu Peng; Mahboob Ali Kalhoro

doi:10.1107/S1600536810051974

. 2010 Dec 18;67(Pt 1):o172–o173. doi: 10.1107/S1600536810051974

{2-[(Benzoyloxy)methyl]-1-oxo-3H-pyrrolizin-2-yl}methyl benzoate

Yousaf Ali ^a,^*, Sammer Yousuf ^b, Nighat Afza ^a, Yu Peng ^c, Mahboob Ali Kalhoro ^a

PMCID: PMC3050358 PMID: 21522679

Abstract

The title compound, C₂₃H₁₉NO₅, was prepared by esterification of 2,2-bis(hydroxymethyl)-2,3-dihydro-1H-pyrrolizin-1-one with benzoyl chloride in pyridine·The pyrrolizine ring system is approximately planar with a maximum deviation of 0.008 (2) Å from the least-squares plane; the two phenyl rings are oriented at dihedral angles of 64.26 (11) and 70.75 (10)° with respect to the pyrrolizine ring system. Weak intermolecular C—H⋯O hydrogen bonding occurs in the crystal structure.

Related literature

For general background to 2,3-dihydropyrrolizine derivatives and for the biological activity of related compounds, see: Skvortsov & Astakhova (1992 ▶); Albrecht et al. (2008 ▶); Morúaa et al. (2009 ▶). For side effects of non-steroidal anti-inflammatory drugs, see: Mishra et al. (2008 ▶). For the synthesis, see: Clemo & Ramage (1931 ▶). For the natural source of the compound, see: Meinwald & Meinwald (1965 ▶). For related structures, see: Ali et al. (2010a ▶,b ▶,c ▶).

Experimental

Crystal data

C₂₃H₁₉NO₅
M _r = 389.39
Triclinic,
a = 8.0438 (8) Å
b = 11.9359 (13) Å
c = 12.0614 (13) Å
α = 64.417 (2)°
β = 72.670 (2)°
γ = 77.390 (2)°
V = 991.65 (18) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 298 K
0.42 × 0.20 × 0.14 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer
13906 measured reflections
4932 independent reflections
3206 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.057
wR(F ²) = 0.161
S = 1.01
4932 reflections
262 parameters
H-atom parameters constrained
Δρ_max = 0.46 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: SMART (Bruker, 2000 ▶); cell refinement: SAINT (Bruker, 2000 ▶); 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: publCIF (Westrip, 2010 ▶) and PLATON (Spek, 2009) ▶.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810051974/xu5119sup1.cif

e-67-0o172-sup1.cif^{(21.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810051974/xu5119Isup2.hkl

e-67-0o172-Isup2.hkl^{(241.5KB, 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
C4—H4A⋯O3ⁱ	0.93	2.59	3.299 (3)	133
C20—H20A⋯O3ⁱⁱ	0.93	2.44	3.269 (3)	149

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

Acknowledgments

YA is grateful to the Industrial Linkage Program of the Pakistan Council of Scientific and Industrial Research, Tianjin University of Science & Technology, China, and the Higher Education Commission of Pakistan for financial support.

supplementary crystallographic information

Comment

Derivatives of 2,3-dihydropyrrolizine became known through studies of their synthesis (Clemo & Ramage, 1931) and isolation from natural source (Meinwald & Meinwald, 1965). Depending on their structure, derivatives of 2,3-dihydropyrrolizine have shown merit as analgesics, anti-inflammatory agents, myorelaxants, inhibitors of thrombocyte aggregation, fibrinolytics, temperature-lowering substances and drugs for the treatment of glaucoma and conjunctivitis (Skvortsov, 1992). The most important of these, Ketorolac, is reported in literature as one of the most effective nonsteroidal anti-inflammatory drugs to alleviate renoureteral colic (Morúaa et al., 2009). But it suffers from the general side effects of NSAIDs, owing to presence of free carboxylic acid group (Mishra et al., 2008). Licofelone(2-[6-(4-Chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro- 1Hpyrrolizin-5-yl] acetic acid) is a dual inhibitor of both cyclooxygenase isoforms and 5-lipoxygenase (Albrecht et al., 2008). Title compound was prepared in order to synthesize new derivatives of this series. Crystal structures of related molecules are reported (Ali et al., 2010a,b,c).

Numbering scheme for single molecule of the title compound is shown in an ORTEP (Farrugia, 1997) plot of the molecule at 50% ellipsoid probability limit (Fig. 1). The two phenyl rings (C1—C6 and C18—C23) and central pyrollizine ring (C9—C15) are each planner with maximum deviation of 0.006 (3)Å for C5, 0.007 (2)Å for C23 and 0.008 (2)Å for C9 atom from the least square planes, respectively. In the crystal structure, the molecules are stabilized, to form a two-dimensional network or infinite chains along z axis (Fig.2), by intermolecular hydrogen bonds C—H···O (Fig.3, symmetry codes as in Table 1).

Experimental

Title compound was prepared by esterification of 2,2-bis(hydroxymethyl)-2,3-dihydro-1H-pyrrolizin- 1-one (1) with benzylchloride (2) (Fig. 4). Thus a mixture of one mole percent of 1 and 1.1 mole percent of 2 was stirred in pyridine at room temperature for three hours. The product was precipitated out by addition of cold water and filtered out to give title compound in good yeild. Final product was purified by Flash Colum Chromatography (Ethyl Acetate: Petroleum Ether = 1:1). Single crystals for X-ray analysis were grown by evaporation from a dilute solution in Ethyl Acetate: Petroleum Ether = 1:1.