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

Ľubomír Švorc; Viktor Vrábel; Jozef Kožíšek; Štefan Marchalín; Peter Šafář

doi:10.1107/S1600536808015456

. 2008 May 30;64(Pt 6):o1164–o1165. doi: 10.1107/S1600536808015456

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

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

PMCID: PMC2961476 PMID: 21202672

Abstract

The absolute configuration of the title compound, C₁₄H₁₃NO₂S, was assigned from the synthesis and confirmed by the structure determination. The central six-membered ring of the indolizine system adopts an envelope conformation, the greatest deviation from the mean plane of the ring being 0.459 (2) Å for the N atom. The benzothieno system is planar [mean deviation = 0.009 (2) Å]. In the crystal structure, molecules form chains parallel to the b axis via intermolecular O—H⋯O hydrogen bonds.

Related literature

For related literature, see: Campagna et al. (1990 ▶); Camus et al. (2000 ▶); Gubin et al. (1992 ▶); Gupta et al. (2003 ▶); Malonne et al. (1998 ▶); Medda et al. (2003 ▶); Mitsumori et al. (2004 ▶); Nardelli (1983 ▶); Ostrander et al. (1988 ▶); Pearson & Guo (2001 ▶); Ruprecht et al. (1989 ▶); Sonnet et al. (2000 ▶); Teklu et al. (2005 ▶); Vlahovici et al. (2002 ▶); Vrábel et al. (2004 ▶); Šafář et al. (2008 ▶).

Experimental

Crystal data

C₁₄H₁₃NO₂S
M _r = 259.31
Orthorhombic,
a = 7.6614 (1) Å
b = 11.7733 (2) Å
c = 13.0736 (2) Å
V = 1179.24 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.27 mm⁻¹
T = 298 (2) K
0.50 × 0.30 × 0.28 mm

Data collection

Oxford Diffraction Gemini R CCD diffractometer
Absorption correction: analytical (Clark & Reid, 1995 ▶) T _min = 0.867, T _max = 0.941
32596 measured reflections
3149 independent reflections
2599 reflections with I > 2σ(I)
R _int = 0.018

Refinement

R[F ² > 2σ(F ²)] = 0.029
wR(F ²) = 0.076
S = 1.04
3149 reflections
165 parameters
H-atom parameters constrained
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.17 e Å⁻³
Absolute structure: Flack (1983 ▶), 1259 Friedel pairs
Flack parameter: 0.01 (6)

Data collection: CrysAlis CCD (Oxford Diffraction, 2006 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2006 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 2001 ▶); software used to prepare material for publication: enCIFer (Allen et al., 2004 ▶).

Supplementary Material

Crystal structure: contains datablocks I. DOI: 10.1107/S1600536808015456/bq2077sup1.cif

e-64-o1164-sup1.cif^{(19.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808015456/bq2077Isup2.hkl

e-64-o1164-Isup2.hkl^{(154.5KB, 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
O2—H2⋯O1ⁱ	0.82	2.00	2.822 (2)	174

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the Grant Agency of the Slovak Republic (grant Nos. 1/0817/08 and 1/0161/08) as well as the Structural Funds, Interreg IIIA, for financial support in the purchase of the diffractometer.

supplementary crystallographic information

Comment

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. They have also shown to be calcium entry blockers (Gupta et al., 2003) and potent antioxidants inhibiting lipid peroxidation in vitro (Teklu et al., 2005). As such, indolizines are important synthetic targets in view of developing new pharmaceuticals for the treatment of cancer (Ostrander et al., 1988), cardiovascular diseases (Gubin et al., 1992) and HIV infections (Ruprecht et al., 1989). Polycyclic indolizine derivatives have been found to have high-efficiency long-wavelength fluorescence quantum yield (Vlahovici et al., 2002). The synthesis of polycyclic indolizine derivatives has recently attracted much research interest in the search for new opto-electric materials (Mitsumori et al., 2004). 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 [absolute structure parameter 0.01 (6) (Flack, 1983)] and assigned consistent with the starting material. The expected stereochemistry of atoms C5 and C6 was confirmed as S and R, respectively (Fig. 1). The central N-heterocyclic ring is not planar and adopts an envelope conformation (Nardelli, 1983). A calculation of least-squares planes shows that this ring is puckered in such a manner that the five atoms C5, C6, C7, C14 and C15 are planar to within 0.061 (3) Å, while atom N1 is displaced from this plane with out-of-plane displacement of 0.459 (2) Å. The pyrrolidin-2-one ring is distorted towards a flat-envelope conformation, with atom C5 on the flap. Atom C5 is 0.291 (2)Å from the mean plane defined by atoms N1, C2, C3 and C4. The molecule as a whole is nonplanar but consist of two approximately planar segments, C5, C6, C7, C8, C9, C10, C11, C12, C13, S1, C14, C15 [r.m.s. deviation 0.086 (2) Å] and N1, C2, O1, C3, C4 [r.m.s. deviation 0.046 (3) Å] with dihedral angle 27.0 (1)°. Atom N1 is sp²-hybridized, as evidenced by the sum of the valence angles around it (358.8°). 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 of (I) into infinite chains, which run parallel to the b axis (Fig. 2 and Table 2) and help to stabilize the crystal structure of the compound. The bond lengths of the carbonyl group C2=O1 is 1.221 (2)Å somewhat longer than typical carbonyl bonds. This may be due to the fact that atom O1 participates in intermolecular hydrogen bond. The bond lengths and angles in the indolizine ring system are comparable with those in related structures (Camus, et al., 2000; Vrábel, et al., 2004).

Experimental

The title compound (11R,11aS)-11-hydroxy-1,5,11,11a-tetrahydro[1] benzothieno[2,3-f]indolizin-3(2H)-one was prepared according literature procedures of Šafář, et al. (2008).