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Acta Crystallogr Sect E Struct Rep Online. 2008 June 1; 64(Pt 6): o1164–o1165.
Published online 2008 May 30. doi:  10.1107/S1600536808015456
PMCID: PMC2961476

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

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 [triangle]); Camus et al. (2000 [triangle]); Gubin et al. (1992 [triangle]); Gupta et al. (2003 [triangle]); Malonne et al. (1998 [triangle]); Medda et al. (2003 [triangle]); Mitsumori et al. (2004 [triangle]); Nardelli (1983 [triangle]); Ostrander et al. (1988 [triangle]); Pearson & Guo (2001 [triangle]); Ruprecht et al. (1989 [triangle]); Sonnet et al. (2000 [triangle]); Teklu et al. (2005 [triangle]); Vlahovici et al. (2002 [triangle]); Vrábel et al. (2004 [triangle]); Šafář et al. (2008 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-o1164-scheme1.jpg

Experimental

Crystal data

  • C14H13NO2S
  • M r = 259.31
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1164-efi1.jpg
  • 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 [triangle]) 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
  • Δρmax = 0.21 e Å−3
  • Δρmin = −0.17 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1259 Friedel pairs
  • Flack parameter: 0.01 (6)

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/S1600536808015456/bq2077sup1.cif

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

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

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).

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 O—H distance 0.85Å and Uiso set at 1.2Ueq of the parent atom. The absolute configuration has been determined. The number of Friedel pairs is 1259.

Figures

Fig. 1.
Molecular structure of (I) with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
Fig. 2.
A packing diagram of the compound (I). Dashed lines indicate hydrogen bonds.

Crystal data

C14H13NO2SF000 = 544
Mr = 259.31Dx = 1.461 Mg m3
Orthorhombic, P212121Mo Kα radiation λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 22009 reflections
a = 7.6614 (1) Åθ = 3.1–26.4º
b = 11.7733 (2) ŵ = 0.27 mm1
c = 13.0736 (2) ÅT = 298 (2) K
V = 1179.24 (3) Å3Block, white
Z = 40.50 × 0.30 × 0.28 mm

Data collection

Oxford Diffraction Gemini R CCD diffractometer3149 independent reflections
Radiation source: fine-focus sealed tube2599 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.019
Detector resolution: 10.4340 pixels mm-1θmax = 26.6º
T = 298(2) Kθmin = 3.1º
Rotation method data acquisition using ω and [var phi] scansh = −10→10
Absorption correction: analytical(Clark & Reid, 1995)k = −16→15
Tmin = 0.867, Tmax = 0.941l = −17→17
32596 measured reflections

Refinement

Refinement on F2H-atom parameters constrained
Least-squares matrix: full  w = 1/[σ2(Fo2) + (0.0357P)2 + 0.2112P] where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.029(Δ/σ)max < 0.001
wR(F2) = 0.076Δρmax = 0.21 e Å3
S = 1.04Δρmin = −0.17 e Å3
3149 reflectionsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
165 parametersExtinction coefficient: 0.0198 (16)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983), 1259 Friedel pairs
Secondary atom site location: difference Fourier mapFlack parameter: 0.01 (6)
Hydrogen site location: inferred from neighbouring sites

Special details

Experimental. face-indexed (CrysAlis RED; Oxford Diffraction, 2006)
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
C20.1944 (2)1.03675 (13)0.20976 (13)0.0455 (3)
C30.1497 (3)1.05817 (14)0.09913 (15)0.0557 (4)
H3A0.05041.10890.09350.067*
H3B0.24801.09160.06340.067*
C40.1063 (3)0.94225 (15)0.05531 (14)0.0582 (5)
H4A0.20140.91470.01310.070*
H4B0.00120.94590.01400.070*
C50.0789 (2)0.86434 (13)0.14788 (12)0.0404 (3)
H5−0.04620.86110.16340.048*
C60.14675 (19)0.74306 (12)0.13407 (10)0.0378 (3)
H60.24560.74620.08660.045*
C70.21221 (18)0.69361 (12)0.23315 (10)0.0354 (3)
C80.27062 (19)0.57799 (12)0.24570 (11)0.0372 (3)
C90.2764 (2)0.48925 (13)0.17477 (12)0.0440 (4)
H90.23860.50100.10800.053*
C100.3382 (2)0.38453 (14)0.20415 (15)0.0509 (4)
H100.34200.32570.15670.061*
C110.3952 (2)0.36526 (14)0.30371 (15)0.0517 (4)
H110.43520.29350.32210.062*
C120.3932 (2)0.45092 (14)0.37530 (14)0.0475 (4)
H120.43220.43830.44170.057*
C130.33100 (19)0.55722 (12)0.34551 (11)0.0397 (3)
C140.23124 (19)0.75541 (12)0.31979 (10)0.0382 (3)
C150.1883 (3)0.87867 (12)0.33040 (11)0.0455 (3)
H15A0.08150.88780.36940.055*
H15B0.28160.91770.36620.055*
N10.16682 (18)0.92626 (10)0.22933 (10)0.0413 (3)
O10.24479 (19)1.10666 (10)0.27209 (11)0.0614 (3)
O20.01482 (15)0.67549 (10)0.08796 (8)0.0503 (3)
H2−0.06010.66010.13060.076*
S10.31793 (6)0.67853 (3)0.42095 (3)0.04613 (11)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C20.0448 (8)0.0367 (7)0.0551 (9)0.0070 (7)0.0090 (8)0.0030 (7)
C30.0607 (10)0.0477 (8)0.0586 (10)0.0112 (8)0.0067 (8)0.0151 (8)
C40.0766 (12)0.0550 (10)0.0431 (9)0.0100 (9)−0.0054 (8)0.0113 (7)
C50.0390 (7)0.0453 (8)0.0369 (7)0.0062 (6)0.0006 (6)0.0016 (6)
C60.0422 (7)0.0422 (7)0.0290 (6)0.0025 (6)0.0025 (5)0.0004 (5)
C70.0382 (7)0.0377 (7)0.0302 (6)−0.0005 (6)0.0023 (5)0.0020 (5)
C80.0360 (7)0.0384 (7)0.0371 (7)−0.0011 (5)0.0027 (6)0.0025 (5)
C90.0455 (9)0.0424 (8)0.0440 (8)0.0016 (6)0.0044 (7)−0.0026 (6)
C100.0487 (9)0.0423 (8)0.0618 (10)0.0047 (7)0.0083 (8)−0.0046 (7)
C110.0423 (8)0.0401 (8)0.0727 (11)0.0050 (7)0.0049 (8)0.0099 (8)
C120.0417 (8)0.0485 (9)0.0523 (9)0.0003 (7)−0.0017 (7)0.0131 (8)
C130.0393 (7)0.0411 (7)0.0389 (7)−0.0018 (6)0.0016 (6)0.0050 (6)
C140.0466 (8)0.0370 (7)0.0309 (6)−0.0023 (6)0.0010 (6)0.0016 (5)
C150.0620 (10)0.0398 (7)0.0348 (7)0.0024 (7)0.0027 (7)−0.0025 (6)
N10.0494 (7)0.0368 (6)0.0377 (6)0.0035 (5)0.0022 (6)0.0005 (5)
O10.0725 (8)0.0396 (6)0.0720 (8)0.0007 (6)0.0049 (7)−0.0072 (6)
O20.0591 (7)0.0554 (6)0.0365 (5)−0.0017 (6)−0.0071 (5)−0.0085 (6)
S10.0593 (2)0.04554 (19)0.03357 (17)−0.00295 (18)−0.00694 (17)0.00349 (16)

Geometric parameters (Å, °)

C2—O11.221 (2)C8—C91.398 (2)
C2—N11.3426 (19)C8—C131.406 (2)
C2—C31.508 (2)C9—C101.375 (2)
C3—C41.517 (3)C9—H90.9300
C3—H3A0.9700C10—C111.392 (3)
C3—H3B0.9700C10—H100.9300
C4—C51.533 (2)C11—C121.376 (3)
C4—H4A0.9700C11—H110.9300
C4—H4B0.9700C12—C131.395 (2)
C5—N11.456 (2)C12—H120.9300
C5—C61.530 (2)C13—S11.7385 (15)
C5—H50.9800C14—C151.494 (2)
C6—O21.4206 (18)C14—S11.7348 (14)
C6—C71.5061 (18)C15—N11.4445 (18)
C6—H60.9800C15—H15A0.9700
C7—C141.3541 (19)C15—H15B0.9700
C7—C81.442 (2)O2—H20.8200
O1—C2—N1125.15 (16)C9—C8—C7129.79 (13)
O1—C2—C3126.83 (15)C13—C8—C7111.83 (12)
N1—C2—C3108.01 (14)C10—C9—C8119.72 (15)
C4—C3—C2105.17 (13)C10—C9—H9120.1
C4—C3—H3A110.7C8—C9—H9120.1
C2—C3—H3A110.7C9—C10—C11121.02 (16)
C4—C3—H3B110.7C9—C10—H10119.5
C2—C3—H3B110.7C11—C10—H10119.5
H3A—C3—H3B108.8C12—C11—C10120.88 (15)
C3—C4—C5105.67 (14)C12—C11—H11119.6
C3—C4—H4A110.6C10—C11—H11119.6
C5—C4—H4A110.6C11—C12—C13118.14 (16)
C3—C4—H4B110.6C11—C12—H12120.9
C5—C4—H4B110.6C13—C12—H12120.9
H4A—C4—H4B108.7C12—C13—C8121.85 (14)
N1—C5—C6113.35 (12)C12—C13—S1126.76 (12)
N1—C5—C4102.39 (13)C8—C13—S1111.39 (11)
C6—C5—C4114.74 (13)C7—C14—C15125.15 (13)
N1—C5—H5108.7C7—C14—S1113.49 (11)
C6—C5—H5108.7C15—C14—S1121.35 (11)
C4—C5—H5108.7N1—C15—C14108.47 (12)
O2—C6—C7112.67 (12)N1—C15—H15A110.0
O2—C6—C5109.32 (12)C14—C15—H15A110.0
C7—C6—C5111.86 (12)N1—C15—H15B110.0
O2—C6—H6107.6C14—C15—H15B110.0
C7—C6—H6107.6H15A—C15—H15B108.4
C5—C6—H6107.6C2—N1—C15122.16 (13)
C14—C7—C8112.24 (12)C2—N1—C5114.75 (13)
C14—C7—C6123.20 (12)C15—N1—C5121.84 (12)
C8—C7—C6124.47 (12)C6—O2—H2109.5
C9—C8—C13118.38 (13)C14—S1—C1391.04 (7)
O1—C2—C3—C4176.43 (17)C9—C8—C13—C12−1.0 (2)
N1—C2—C3—C4−4.46 (19)C7—C8—C13—C12179.72 (14)
C2—C3—C4—C515.15 (19)C9—C8—C13—S1178.57 (12)
C3—C4—C5—N1−19.57 (18)C7—C8—C13—S1−0.73 (16)
C3—C4—C5—C6−142.81 (14)C8—C7—C14—C15177.89 (15)
N1—C5—C6—O2155.60 (12)C6—C7—C14—C151.1 (2)
C4—C5—C6—O2−87.26 (15)C8—C7—C14—S1−0.54 (16)
N1—C5—C6—C730.10 (17)C6—C7—C14—S1−177.34 (11)
C4—C5—C6—C7147.24 (14)C7—C14—C15—N1−14.4 (2)
O2—C6—C7—C14−132.48 (14)S1—C14—C15—N1163.94 (11)
C5—C6—C7—C14−8.85 (19)O1—C2—N1—C152.6 (3)
O2—C6—C7—C851.11 (18)C3—C2—N1—C15−176.58 (15)
C5—C6—C7—C8174.74 (13)O1—C2—N1—C5169.96 (16)
C14—C7—C8—C9−178.38 (16)C3—C2—N1—C5−9.17 (18)
C6—C7—C8—C9−1.6 (2)C14—C15—N1—C2−153.70 (14)
C14—C7—C8—C130.81 (18)C14—C15—N1—C539.8 (2)
C6—C7—C8—C13177.57 (13)C6—C5—N1—C2142.58 (13)
C13—C8—C9—C100.8 (2)C4—C5—N1—C218.41 (17)
C7—C8—C9—C10179.94 (16)C6—C5—N1—C15−49.97 (19)
C8—C9—C10—C110.1 (3)C4—C5—N1—C15−174.13 (15)
C9—C10—C11—C12−0.8 (3)C7—C14—S1—C130.10 (12)
C10—C11—C12—C130.6 (2)C15—C14—S1—C13−178.39 (13)
C11—C12—C13—C80.3 (2)C12—C13—S1—C14179.90 (14)
C11—C12—C13—S1−179.18 (12)C8—C13—S1—C140.37 (12)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O2—H2···O1i0.822.002.822 (2)174

Symmetry codes: (i) −x, y−1/2, −z+1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BQ2077).

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