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Acta Crystallogr Sect E Struct Rep Online. 2009 April 1; 65(Pt 4): o695–o696.
Published online 2009 March 6. doi:  10.1107/S1600536809007405
PMCID: PMC2968850

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

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

An external file that holds a picture, illustration, etc.
Object name is e-65-0o695-scheme1.jpg

Experimental

Crystal data

  • C10H11NOS
  • M r = 193.26
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-0o695-efi1.jpg
  • 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 [triangle]) 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
  • Δρmax = 0.41 e Å−3
  • Δρmin = −0.21 e Å−3

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

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I. DOI: 10.1107/S1600536809007405/bg2239sup1.cif

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

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

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).

Refinement

All H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C—H distances in the range 0.93 - 0.98Å and Uiso set at 1.2Ueq of the parent atom. The absolute configuration could not be reliably determined for this compound using Mo radiation, and has been assigned according to the synthesis.

Figures

Fig. 1.
Molecular structure of (I) with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level (Brandenburg, 2001).

Crystal data

C10H11NOSZ = 2
Mr = 193.26F(000) = 204
Triclinic, P1Dx = 1.395 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 6.37912 (16) ÅCell parameters from 12211 reflections
b = 8.3654 (3) Åθ = 3.3–29.4°
c = 9.0715 (3) ŵ = 0.31 mm1
α = 84.180 (3)°T = 298 K
β = 78.611 (2)°Block, colourless
γ = 76.174 (3)°0.42 × 0.32 × 0.14 mm
V = 460.06 (3) Å3

Data collection

Oxford Diffraction Gemini R CCD diffractometer2348 independent reflections
Radiation source: fine-focus sealed tube1918 reflections with I > 2σ(I)
graphiteRint = 0.018
Detector resolution: 10.4340 pixels mm-1θmax = 29.5°, θmin = 3.3°
Rotation method data acquisition using ω and [var phi] scansh = −8→8
Absorption correction: analytical (Clark & Reid, 1995)k = −11→11
Tmin = 0.824, Tmax = 0.928l = −12→12
20197 measured reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.118H-atom parameters constrained
S = 1.06w = 1/[σ2(Fo2) + (0.0629P)2 + 0.1103P] where P = (Fo2 + 2Fc2)/3
2348 reflections(Δ/σ)max < 0.001
118 parametersΔρmax = 0.41 e Å3
0 restraintsΔρmin = −0.21 e Å3

Special details

Experimental. face-indexed (CrysAlis RED; Oxford Diffraction, 2006)The absolute configuration could not be reliably determined for this compound using Mo-radiation, and has been assigned according to the synthesis.
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
C20.1565 (3)0.7697 (2)1.25520 (17)0.0449 (4)
C30.2584 (3)0.6972 (2)1.39075 (18)0.0519 (4)
H3B0.18630.61331.44490.062*
H3A0.24850.78211.45880.062*
C40.4980 (3)0.6222 (2)1.32515 (17)0.0482 (4)
H4B0.59520.63731.38990.058*
H4A0.51960.50541.31200.058*
C50.5387 (2)0.7177 (2)1.17316 (16)0.0411 (3)
H5A0.58410.81801.18800.049*
C60.7046 (2)0.6242 (2)1.05152 (16)0.0437 (3)
H6B0.85190.62051.06710.052*
H6A0.68660.51181.05510.052*
C70.6721 (2)0.70843 (18)0.90130 (16)0.0397 (3)
C80.6992 (3)0.8129 (2)0.63501 (19)0.0548 (4)
H8A0.73850.83950.53280.066*
C90.4964 (3)0.8674 (2)0.71745 (17)0.0481 (4)
H9A0.38070.93620.67790.058*
C100.4802 (2)0.80769 (17)0.87139 (16)0.0370 (3)
C110.2797 (2)0.84994 (19)0.99057 (16)0.0413 (3)
H11B0.24130.96801.00200.050*
H11A0.15770.81930.96030.050*
N10.31810 (18)0.76400 (15)1.13355 (13)0.0369 (3)
O1−0.03879 (19)0.82620 (19)1.25376 (15)0.0653 (4)
S10.87330 (7)0.68901 (6)0.74263 (5)0.05585 (18)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C20.0358 (8)0.0559 (9)0.0399 (8)−0.0084 (6)−0.0014 (6)−0.0036 (6)
C30.0459 (9)0.0707 (11)0.0334 (7)−0.0092 (8)0.0004 (6)−0.0006 (7)
C40.0413 (8)0.0636 (10)0.0350 (7)−0.0049 (7)−0.0079 (6)0.0042 (7)
C50.0320 (7)0.0511 (8)0.0376 (7)−0.0046 (6)−0.0068 (6)−0.0004 (6)
C60.0346 (7)0.0518 (8)0.0373 (7)0.0008 (6)−0.0045 (6)0.0026 (6)
C70.0367 (7)0.0445 (8)0.0326 (7)−0.0041 (6)−0.0008 (5)−0.0010 (5)
C80.0668 (11)0.0585 (10)0.0321 (7)−0.0093 (8)−0.0013 (7)0.0036 (7)
C90.0583 (10)0.0458 (8)0.0356 (7)−0.0038 (7)−0.0100 (7)0.0035 (6)
C100.0392 (7)0.0362 (7)0.0335 (7)−0.0055 (5)−0.0056 (5)−0.0007 (5)
C110.0356 (7)0.0445 (8)0.0385 (7)−0.0007 (6)−0.0070 (6)0.0028 (6)
N10.0290 (6)0.0456 (6)0.0328 (6)−0.0039 (5)−0.0047 (4)0.0009 (5)
O10.0320 (6)0.0977 (10)0.0558 (7)−0.0034 (6)0.0003 (5)0.0010 (7)
S10.0463 (3)0.0700 (3)0.0387 (2)−0.00116 (19)0.00624 (17)−0.00050 (18)

Geometric parameters (Å, °)

C2—O11.2244 (19)C6—H6B0.9700
C2—N11.3494 (19)C6—H6A0.9700
C2—C31.509 (2)C7—C101.364 (2)
C3—C41.531 (2)C7—S11.7216 (15)
C3—H3B0.9700C8—C91.359 (3)
C3—H3A0.9700C8—S11.7127 (19)
C4—C51.530 (2)C8—H8A0.9300
C4—H4B0.9700C9—C101.4271 (19)
C4—H4A0.9700C9—H9A0.9300
C5—N11.4730 (18)C10—C111.4983 (19)
C5—C61.506 (2)C11—N11.4530 (18)
C5—H5A0.9800C11—H11B0.9700
C6—C71.498 (2)C11—H11A0.9700
O1—C2—N1124.92 (15)C5—C6—H6A109.9
O1—C2—C3126.64 (15)H6B—C6—H6A108.3
N1—C2—C3108.44 (13)C10—C7—C6124.86 (13)
C2—C3—C4104.44 (13)C10—C7—S1111.24 (11)
C2—C3—H3B110.9C6—C7—S1123.89 (11)
C4—C3—H3B110.9C9—C8—S1111.60 (12)
C2—C3—H3A110.9C9—C8—H8A124.2
C4—C3—H3A110.9S1—C8—H8A124.2
H3B—C3—H3A108.9C8—C9—C10112.69 (15)
C5—C4—C3103.88 (13)C8—C9—H9A123.7
C5—C4—H4B111.0C10—C9—H9A123.7
C3—C4—H4B111.0C7—C10—C9112.41 (14)
C5—C4—H4A111.0C7—C10—C11122.46 (13)
C3—C4—H4A111.0C9—C10—C11125.11 (13)
H4B—C4—H4A109.0N1—C11—C10110.65 (12)
N1—C5—C6111.65 (12)N1—C11—H11B109.5
N1—C5—C4102.22 (12)C10—C11—H11B109.5
C6—C5—C4115.73 (14)N1—C11—H11A109.5
N1—C5—H5A109.0C10—C11—H11A109.5
C6—C5—H5A109.0H11B—C11—H11A108.1
C4—C5—H5A109.0C2—N1—C11122.02 (12)
C7—C6—C5109.13 (12)C2—N1—C5112.77 (12)
C7—C6—H6B109.9C11—N1—C5121.72 (12)
C5—C6—H6B109.9C8—S1—C792.04 (8)
C7—C6—H6A109.9
O1—C2—C3—C4171.40 (18)C7—C10—C11—N1−3.3 (2)
N1—C2—C3—C4−9.31 (19)C9—C10—C11—N1178.30 (14)
C2—C3—C4—C523.40 (19)O1—C2—N1—C1110.3 (3)
C3—C4—C5—N1−28.18 (17)C3—C2—N1—C11−168.98 (14)
C3—C4—C5—C6−149.74 (14)O1—C2—N1—C5169.56 (17)
N1—C5—C6—C744.61 (18)C3—C2—N1—C5−9.74 (18)
C4—C5—C6—C7160.97 (13)C10—C11—N1—C2−173.84 (13)
C5—C6—C7—C10−24.2 (2)C10—C11—N1—C528.76 (19)
C5—C6—C7—S1156.95 (12)C6—C5—N1—C2148.74 (14)
S1—C8—C9—C10−0.2 (2)C4—C5—N1—C224.42 (17)
C6—C7—C10—C9−178.47 (14)C6—C5—N1—C11−51.94 (19)
S1—C7—C10—C90.54 (17)C4—C5—N1—C11−176.27 (13)
C6—C7—C10—C112.9 (2)C9—C8—S1—C70.39 (15)
S1—C7—C10—C11−178.07 (11)C10—C7—S1—C8−0.53 (13)
C8—C9—C10—C7−0.3 (2)C6—C7—S1—C8178.49 (15)
C8—C9—C10—C11178.31 (15)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C9—H9A···O1i0.932.603.379 (2)142

Symmetry codes: (i) −x, −y+2, −z+2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BG2239).

References

  • Allen, F. H., Johnson, O., Shields, G. P., Smith, B. R. & Towler, M. (2004). J. Appl. Cryst.37, 335–338.
  • Brandenburg, K. (2001). DIAMOND Crystal Impact GbR, Bonn, Germany.
  • Brandi, A., Cicchi, S., Cordero, F. M., Frignoli, R., Goti, A., Picasso, S. & Vogel, P. (1995). J. Org. Chem.60, 6806–6812.
  • Brown, C. J. & Corbridge, D. E. C. (1954). Acta Cryst.7, 711–715.
  • Campagna, F., Carotti, A., Casini, G. & Macripo, M. (1990). Heterocycles, 31, 97–107.
  • Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887–897.
  • Couture, A., Deniau, E., Grandclaudon, P., Leburn, S., Leonce, S., Renard, P. & Pfeiffer, B. (2000). Bioorg. Med. Chem.8, 2113–2125. [PubMed]
  • Gubin, J., Lucchetti, J., Mahaux, J., Nisato, D., Rosseels, G., Clinet, M., Polster, P. & Chatelain, P. (1992). J. Med. Chem.35, 981–988. [PubMed]
  • Gundersen, L. L., Negussie, A. H., Rise, F. & Ostby, O. B. (2003). Arch. Pharm. (Weinheim), 336, 191–195. [PubMed]
  • Gupta, S. P., Mathur, A. N., Nagappa, A. N., Kumar, D. & Kumaran, S. (2003). Eur. J. Med. Chem.38, 867–873. [PubMed]
  • Hema, R., Parthasarathi, V., Sarkunam, K., Nallu, M. & Linden, A. (2003). Acta Cryst. C59, o703–o705. [PubMed]
  • Hempel, A., Camerman, N., Mastropaolo, D. & Camerman, A. (1993). J. Med. Chem.36, 4082–4086. [PubMed]
  • Jorgensen, A. S., Jacobsen, P., Chirstiansen, L. B., Bury, P. S., Kanstrup, A., Thorp, S. M., Bain, S., Naerum, L. & Wasserman, K. (2000). Bioorg. Med. Chem. Lett.10, 399–402. [PubMed]
  • Malonne, H., Hanuise, J. & Fontaine, J. (1998). Pharm. Pharmacol. Commun.4, 241–243.
  • Marchalín, Š., Szemes, F., Bar, N. & Decroix, B. (2008). Heterocycles, 50, 445–452.
  • Medda, S., Jaisankar, P., Manna, R. K., Pal, B., Giri, V. S. & Basu, M. K. (2003). J. Drug Target.11, 123–128. [PubMed]
  • Nardelli, M. (1983). Acta Cryst. C39, 1141–1142.
  • Oxford Diffraction (2006). CrysAlis CCD and CrysAlis RED Oxford Diffraction Ltd, Abingdon, England.
  • Pearson, W. H. & Guo, L. (2001). Tetrahedron Lett.42, 8267–8271.
  • Pedersen, B. F. (1967). Acta Chem. Scand.21, 1415–1424.
  • Poty, C., Gibon, V., Evrard, G., Norberg, B., Vercauteren, D. P., Gubin, J., Chatelain, P. & Durant, F. (1994). Eur. J. Med. Chem.29, 911–923.
  • Rosseels, G., Peiren, M., Inion, H., Deray, E., Prost, M., Descamps, M., Bauthier, J., Richard, J., Tornay, C., Colot, M. & Claviere, M. (1982). Eur. J. Med. Chem.17, 581–584.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Sonnet, P., Dallemagne, P., Guillom, J., Engueard, C., Stiebing, S., Tangue, J., Bureau, B., Rault, S., Auvray, P., Moslemi, S., Sourdaine, P. & Seralini, G. E. (2000). Bioorg. Med. Chem.8, 945–955. [PubMed]
  • Švorc, Ľ., Vrábel, V., Kožíšek, J., Marchalín, Š. & Žúžiová, J. (2007). Acta Cryst. E63, o1452–o1454.
  • Vlahovici, A., Andrei, M. & Druta, I. (2002). J. Lumin.96, 279–285.
  • Vrábel, V., Kožíšek, J., Langer, V. & Marchalín, Š. (2004). Acta Cryst. E60, o932–o933.

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