(8aS)-7,8,8a,9-Tetra­hydro­thieno[3,2-f]indolizin-6(4H)-one

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

doi:10.1107/S1600536809007405

. 2009 Mar 6;65(Pt 4):o695–o696. doi: 10.1107/S1600536809007405

(8aS)-7,8,8a,9-Tetrahydrothieno[3,2-f]indolizin-6(4H)-one

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

PMCID: PMC2968850 PMID: 21582436

Abstract

In the molecular structure of the title compound, C₁₀H₁₁NOS, the central six-membered ring of the indolizine unit adopts an envelope conformation, the maximum deviations from the mean plane of the ring being 0.533 (2) Å. The fused thieno ring is nearly coplanar [mean deviation = 0.007 (2) Å]. The conformation of the fused oxopyrrolidine ring is close to that of a flat-envelope, with a maximum deviation of 0.339 (3) Å. The crystal structure is stabilized by C—H⋯O hydrogen bonds.

Related literature

For general applications of indolizine derivatives, see: Brandi et al. (1995 ▶); Campagna et al. (1990 ▶); Couture et al. (2000 ▶); Gubin et al. (1992 ▶); Gundersen et al. (2003 ▶); Gupta et al. (2003 ▶); Hema et al. (2003 ▶); Hempel et al. (1993 ▶); Jorgensen et al. (2000 ▶); Malonne et al. (1998 ▶); Marchalín et al. (2008 ▶); Medda et al. (2003 ▶); Nardelli (1983 ▶); Pearson & Guo (2001 ▶); Poty et al. (1994 ▶); Rosseels et al. (1982 ▶); Sonnet et al. (2000 ▶); Vlahovici et al. (2002 ▶); Vrábel et al. (2004 ▶); Švorc et al. (2007 ▶). For bond-length data, see: Brown & Corbridge (1954 ▶); Pedersen (1967 ▶).

Experimental

Crystal data

C₁₀H₁₁NOS
M _r = 193.26
Triclinic,
a = 6.37912 (16) Å
b = 8.3654 (3) Å
c = 9.0715 (3) Å
α = 84.180 (3)°
β = 78.611 (2)°
γ = 76.174 (3)°
V = 460.06 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.31 mm⁻¹
T = 298 K
0.42 × 0.32 × 0.14 mm

Data collection

Oxford Diffraction Gemini R CCD diffractometer
Absorption correction: analytical (Clark & Reid, 1995 ▶) T _min = 0.824, T _max = 0.928
20197 measured reflections
2348 independent reflections
1918 reflections with I > 2σ(I)
R _int = 0.018

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.118
S = 1.06
2348 reflections
118 parameters
H-atom parameters constrained
Δρ_max = 0.41 e Å⁻³
Δρ_min = −0.21 e Å⁻³

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/S1600536809007405/bg2239sup1.cif

e-65-0o695-sup1.cif^{(16.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809007405/bg2239Isup2.hkl

e-65-0o695-Isup2.hkl^{(115.4KB, 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
C9—H9A⋯O1ⁱ	0.93	2.60	3.379 (2)	142

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the Grant Agency of the Slovak Republic (grant Nos. 1/0161/08 and 1/0817/08) and the Structural Funds, Interreg IIIA for financial support to purchase the diffractometer and the Development Agency under contract No. APVV-0210–07.

supplementary crystallographic information

Comment

Indolizines, the nitrogen containing heterocyclic systems, are widely distributed in nature; in particular, indolizine derivatives are an important class of heterocyclic bioactive compounds with a wide range of applications, such as pharmaceutical drugs, potential central nervous system depressants, calcium entry blockers, cardiovascular agents, spectral sensitizers and novel dyes (Gubin et al., 1992; Gupta et al., 2003; Poty et al., 1994; Hema et al., 2003). Polycyclic indolizine derivatives have been found to have high-efficiency long-wavelength fluorescence quantum yield (Vlahovici et al., 2002). Several polyhydroxylated indolizines are interesting as inhibitors of glycosides (Hempel et al., 1993; Brandi et al., 1995). They have also been tested as antimycobacterial agents against mycobacterial tuberculosis (Gundersen et al., 2003), for the treatment of angina pectoris (Rosseels et al., 1982), aromatase inhibitory (Sonnet et al., 2000), antiinflammatory (Malonne et al., 1998), antiviral (Medda et al., 2003), analgestic (Campagna et al., 1990) and antitumor (Pearson & Guo, 2001) activities. The other well known pharmacological applications associated with this ring compounds are well documented in the literature (Couture et al., 2000; Jorgensen et al., 2000). These findings had led to a spate of synthetic and structural studies of various indolizine analogues.

Based on these facts and in continutation of our interest in developing simple and efficient routes for the synthesis of novel indolizine derivatives, we report here the synthesis, molecular and crystal structure of the title compound, (I). The absolute configuration is known from the synthesis and is depicted in the scheme and Figure 1. The expected stereochemistry of atom C5 was confirmed as S. 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 N1, C11, C10, C7 and C6 are coplanar to within 0.032 (3) Å, while atom C5 is displaced from this plane with out-of-plane displacement of 0.533 (2) Å. The fused thieno ring is nearly coplanar [mean deviation = 0.007 (2) Å]. The oxopyrrolidine ring attached to the indolizine ring system has flat-envelope conformation with atom C5 on the flap. The deviation of atom C5 from the mean plane of the remaining four atoms N1/C2/C3/C4 is 0.339 (3) Å. The N1—C5 and N1—C11 bonds are approximately equivalent and both are much longer than the N1—C2 bond. Moreover, the N1 atom is sp² hybridized, as evidenced by the sum of the valence angles around it [356.1 (1)°]. These data are consistent with conjugation of the lone-pair electrons on N1 with the adjacent carbonyl and agree with literature values for simple amides (Brown & Corbridge, 1954; Pedersen, 1967). The bond length of the carbonyl group C2=O1 is 1.224 (2) Å, respectively, is somewhat longer than typical carbonyl bonds. This may be due to the fact that atom O1 participates in intermolecular C–H···O hydrogen bonds with atom C9 (Table 2). The bond lengths and angles in the molecule are comparable with those in a related structure (Vrábel et al., 2004,Švorc et al., 2007).

Experimental

Triethylsilane (2.4 ml, 15 mmol) was added to a stirred solution of alcohol (2.1 g, 10 mmol) in trifluoroacetic acid (20 ml) at 0 °C, and the resulting yellow solution was stirred at rt for 2 h. The reaction mixture was concentrated in vacuo, diluted with water (50 ml), made alkaline with 10% Na₂CO₃, and then extracted with dichloromethane (3 x 50 ml). The extract was washed with water, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography on a silica gel column eluting with dichloromethane. Recrystallization of a solid from cyclohexane gaves amide as colorless crystals (Marchalín et al. 2008).