(5S,11aS)-5-Hydro­per­oxy-1,5,11,11a-tetra­hydro­[1]benzothieno[3,2-f]indol­izin-3(2H)-one

Viktor Vrábel; Ľubomír Švorc; Štefan Marchalín; Peter Šafář

doi:10.1107/S1600536812045394

. 2012 Nov 10;68(Pt 12):o3327–o3328. doi: 10.1107/S1600536812045394

(5S,11aS)-5-Hydroperoxy-1,5,11,11a-tetrahydro[1]benzothieno[3,2-f]indolizin-3(2H)-one

Viktor Vrábel ^a,^*, Ľubomír Švorc ^a, Štefan Marchalín ^b, Peter Šafář ^b

PMCID: PMC3588932 PMID: 23476168

Abstract

The absolute configuration of the title compound, C₁₄H₁₃NO₃S, was assigned from the synthesis and confirmed by the structure determination. The central six-membered ring of the indolizine moiety adopts an envelope conformation, with the greatest deviation from the mean plane of the ring being 0.661 (2) Å for the bridgehead C atom. The benzothiene ring attached to the indolizine ring system is planar to within 0.008 (2) Å. In the crystal, molecules form chains parallel to the b axis via O—H⋯O hydrogen bonds.

Related literature

For background to indolizines and their biological activity, see: Malonne et al. (1998 ▶); Medda et al. (2003 ▶); Sonnet et al. (2000 ▶); Campagna et al. (1990 ▶); Pearson & Guo (2001 ▶). For their synthesis, see: Šafář et al. (2009a ▶,b ▶). For compounds with similar properties, see: Švorc et al. (2008 ▶, 2009 ▶). For IR spectroscopy on similar compounds, see: Šafář et al. (2009a ▶). For conformational analysis, see: Nardelli (1983 ▶).

Experimental

Crystal data

C₁₄H₁₃NO₃S
M _r = 275.31
Monoclinic,
a = 7.8040 (5) Å
b = 7.9800 (4) Å
c = 10.2903 (5) Å
β = 99.458 (5)°
V = 632.13 (6) Å³
Z = 2
Mo Kα radiation
μ = 0.26 mm⁻¹
T = 295 K
0.25 × 0.20 × 0.15 mm

Data collection

Oxford Diffraction Xcalibur (Ruby, Gemi) diffractometer
Absorption correction: analytical [CrysAlis RED (Oxford Diffraction, 2009 ▶), based on expressions derived by Clark & Reid (1995 ▶)] T _min = 0.947, T _max = 0.974
21595 measured reflections
2555 independent reflections
2162 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.027
wR(F ²) = 0.068
S = 1.00
2555 reflections
176 parameters
2 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.14 e Å⁻³
Absolute structure: Flack (1983 ▶), 1185 Friedel pairs
Flack parameter: −0.05 (6)

Data collection: CrysAlis CCD (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2009 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND, (Brandenburg, 2001 ▶), PLATON (Spek, 2009 ▶) and WinGX (Farrugia, 1999 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Click here for additional data file.^{(20.6KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812045394/bg2481sup1.cif

e-68-o3327-sup1.cif^{(20.6KB, cif)}

Click here for additional data file.^{(125.5KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812045394/bg2481Isup2.hkl

e-68-o3327-Isup2.hkl^{(125.5KB, hkl)}

Click here for additional data file.^{(5.3KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536812045394/bg2481Isup3.cml

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
O3—H3⋯O1ⁱ	0.84 (1)	1.86 (1)	2.6962 (19)	173 (2)

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the Grant Agency of Slovak Republic, Grant Nos. 1/0429/11, 1/0679/11 and the Slovak Research and Development Agency under contract Nos. APVV-0797–11 and APVV-0204–10 for financial support for this research program.

supplementary crystallographic information

Comment

Heterocycles are involved in a wide range of biologically important chemical reactions in living organisms, and therefore they form one of the most important and well investigated classes of organic compounds. One group of heterocycles, indolizines, has received much scientific attention during the recent years. Indolizine derivatives have been found to possess a variety of biological activities such as antiinflammatory (Malonne et al., 1998), antiviral (Medda et al., 2003), aromatase inhibitory (Sonnet et al., 2000), analgestic (Campagna et al., 1990) and antitumor (Pearson & Guo, 2001) activities. As part of our recent efforts to synthesize novel polycyclic indolizine derivative, we report here the synthesis and molecular and crystal structure of the title compound, (I) (Fig. 1). The absolute configuration has been established without ambiguity from the anomalous dispersion of the S atom (Flack, 1983) and assigned consistent with the starting material. The expected stereochemistry of both atoms C5 and C15 was confirmed as S, see Fig. 1. The central N-heterocyclic ring is not planar and adopts a envelope conformation (Nardelli, 1983). A calculation of least-squares planes shows that this ring is puckered in such a manner that the five atoms C6, C7, C14, C15 and N1 are planar to within 0.075 (3) Å, while atom C5 is displaced from this plane with out-of-plane displacement of 0.661 (2) Å. The pyrrolidine ring is distorted towards a flat-envelope conformation, with atom C4 on the flap. Atom C4 is 0.402 (2) Å from the mean plane defined by atoms C5, N1, C2 and C3. The dihedral angle between the plane of the central N-heterocyclic ring and the plane of the pyrrolidine ring is 44.6 (1)°. Atom N1 is sp²-hybridized, as evidenced by the sum of the valence angles around it (358.1°). These data are consistent with conjugation of the lone-pair electrons on N1 with the adjacent carbonyl, similar to what is observed for amides. Intermolecular O—H···O hydrogen bonds link the molecules into infinite chains, which run parallel to the b axis (Fig. 2) and help to stabilize the crystal structure of the compound. The bond lengths of the carbonyl group C2=O1 is 1.233 (2) Å somewhat longer than typical carbonyl bonds. This may be due to the fact that atom O1 participates in intermolecular hydrogen bond.

Experimental

To a solution of (11aS)-1,5,11,11a-tetrahydro[1]benzothieno[3,2-f] indolizin-3(2H)-one (0.041 mmol) in THF (2 ml) was added 3 drops of H₂O₂ at 0°C and the mixture was allowed to react at room temperature for 72 h. The colorless crystals were filtered off, and washing with dry n-hexane (1 ml) gave pure indolizinhydroperoxid.