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Acta Crystallogr Sect E Struct Rep Online. 2010 September 1; 66(Pt 9): o2431.
Published online 2010 August 28. doi:  10.1107/S160053681003285X
PMCID: PMC3008056

7′-Methyl-5′-oxo-2′,3′-dihydro­spiro­[1,3-dioxolane-2,1′(5′H)-indolizine]-6′-carbonitrile

Abstract

In the title compound, C12H12N2O3, the five-membered ring attached to the aromatic ring adopts an envelope conformation with a C atom in the flap position. The spiro-linked five-membered ring adopts a twisted conformation. In the crystal, C—H(...)O hydrogen bonds link the mol­ecules into C(5) chains propagating in [001].

Related literature

For medicinal background, see: Takimoto & Calvo (2008 [triangle]). For further synthetic details, see: Wani et al. (1980 [triangle]). For bond-length data, see: Allen et al. (1987 [triangle]).

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Object name is e-66-o2431-scheme1.jpg

Experimental

Crystal data

  • C12H12N2O3
  • M r = 232.24
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2431-efi1.jpg
  • a = 7.9460 (16) Å
  • b = 25.945 (5) Å
  • c = 5.3430 (11) Å
  • V = 1101.5 (4) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 293 K
  • 0.30 × 0.10 × 0.10 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: ψ scan (North et al., 1968 [triangle]) T min = 0.970, T max = 0.990
  • 2217 measured reflections
  • 1123 independent reflections
  • 821 reflections with I > 2σ(I)
  • R int = 0.035
  • 3 standard reflections every 200 reflections intensity decay: 1%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.046
  • wR(F 2) = 0.112
  • S = 1.00
  • 1123 reflections
  • 155 parameters
  • 1 restraint
  • H-atom parameters constrained
  • Δρmax = 0.20 e Å−3
  • Δρmin = −0.20 e Å−3

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 [triangle]); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681003285X/hb5573sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053681003285X/hb5573Isup2.hkl

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

Acknowledgments

This research work was supported financially by the Department of Science and Technology of Jiangsu Province (BE200830457) and the ‘863’ project (2007 A A02Z211) of the Ministry of Science and Technology of China.

supplementary crystallographic information

Comment

Camptothecin(CPT), with the chemical name (S)-4-ethyl-4-hydroxy-1H-pyr- ano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-(4H,12H)-dione, is a pentacyclic alkaloid. Two CPT analogues, topotecan and irinotecan, have been approved and are used in cancer chemotherapy (Takimoto & Calvo, 2008). As part of our studies into the synthesis of Camptothecin, the title compound, (I), was synthesized (Wani et al., 1980). We report herein the crystal structure of the title compound.

In the molecule of the title compound, (Fig. 1), the bond lengths (Allen et al., 1987) and angles are within normal ranges. In the crystal structure, C—H···O hydrogen bonds link the molecules (Fig. 2), based on the geometrically positioned H5B atom, in which they may be effective in the stabilization of the structure.

Experimental

A mixture of 1,2,3,5-tetrahydro-7-methyl-1,5-dioxo-6- Indolizinecarbonitrile, (13.0 g,0.069 mol), ethylene glycol (210 ml), and p-toluenesulfonic acid (1.1 g) in toluene (1.0 L) was refluxed using a Dean-Stark trap for 5 h. The toluene layer was decanted and another liter of toluene was added. The reaction mixture was refluxed for an additional 5 h and the toluene layer decanted as before. After repeating this procedure two more times, the toluene layers were combined, washed with brine, dried, and evaporated to yield the crude product, which was crystallized from MeOH to give the title compound (93%) (Wani et al., 1980). Colourless blocks of (I) were obtained by slow evaporation of an MeOH solution.

Refinement

Anomalous dispersion was negligible and Friedel pairs were merged before refinement. H atoms were positioned geometrically with C—H = 0.93, 0.98 and 0.97 Å for aromatic, methine and methylene H atoms, respectively, and constrained to ride on their parent atoms, with Uiso(H) = 1.2 (or 1.5 for methyl groups) times Ueq(C).

Figures

Fig. 1.
The molecular structure of (I) with displacement ellipsoids are drawn at 30% probability levels.
Fig. 2.
A practical packing diagram of the title compound. Hydron bonds are shown as dashed lines.

Crystal data

C12H12N2O3Dx = 1.400 Mg m3
Mr = 232.24Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pna21Cell parameters from 25 reflections
a = 7.9460 (16) Åθ = 9–12°
b = 25.945 (5) ŵ = 0.10 mm1
c = 5.3430 (11) ÅT = 293 K
V = 1101.5 (4) Å3Block, colorless
Z = 40.30 × 0.10 × 0.10 mm
F(000) = 488

Data collection

Enraf–Nonius CAD-4 diffractometer821 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.035
graphiteθmax = 25.3°, θmin = 1.6°
ω/2θ scansh = 0→9
Absorption correction: ψ scan (North et al., 1968)k = −31→31
Tmin = 0.970, Tmax = 0.990l = 0→6
2217 measured reflections3 standard reflections every 200 reflections
1123 independent reflections intensity decay: 1%

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.046H-atom parameters constrained
wR(F2) = 0.112w = 1/[σ2(Fo2) + (0.063P)2] where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
1123 reflectionsΔρmax = 0.20 e Å3
155 parametersΔρmin = −0.20 e Å3
1 restraintExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.047 (6)

Special details

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
N10.6878 (4)0.41701 (10)0.1075 (7)0.0350 (8)
O11.0548 (3)0.42931 (10)−0.0779 (6)0.0432 (7)
C11.1570 (5)0.39063 (18)−0.1891 (10)0.0523 (12)
H1A1.14990.3586−0.09630.063*
H1B1.27370.4015−0.19650.063*
O20.9270 (3)0.41052 (10)−0.4426 (6)0.0464 (8)
C21.0842 (5)0.38466 (17)−0.4486 (10)0.0532 (12)
H2A1.15790.4001−0.57240.064*
H2B1.06900.3485−0.48920.064*
N20.3916 (5)0.29581 (15)0.6093 (9)0.0675 (12)
O30.5035 (3)0.42382 (11)0.4332 (7)0.0551 (8)
C30.8959 (5)0.42629 (15)−0.1938 (8)0.0382 (9)
C40.7840 (4)0.38909 (13)−0.0515 (8)0.0330 (8)
C50.7124 (5)0.47294 (14)0.0789 (9)0.0435 (10)
H5A0.78000.48680.21420.052*
H5B0.60550.49100.07350.052*
C60.8043 (5)0.47679 (15)−0.1705 (9)0.0465 (11)
H6A0.72540.4813−0.30720.056*
H6B0.88280.5054−0.17010.056*
C70.7736 (4)0.33684 (13)−0.0581 (8)0.0378 (9)
H7A0.83640.3182−0.17360.045*
C80.6665 (4)0.31108 (13)0.1120 (8)0.0361 (9)
C90.5774 (4)0.34061 (15)0.2809 (8)0.0384 (9)
C100.5825 (5)0.39580 (15)0.2880 (8)0.0411 (10)
C110.6517 (5)0.25394 (13)0.1031 (9)0.0484 (11)
H11A0.57470.24260.23010.073*
H11B0.76020.23870.13180.073*
H11C0.61070.2436−0.05830.073*
C120.4728 (5)0.31630 (16)0.4644 (10)0.0451 (10)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0381 (16)0.0350 (16)0.0320 (18)0.0017 (13)0.0036 (16)−0.0016 (17)
O10.0423 (14)0.0509 (14)0.0365 (15)−0.0026 (13)0.0029 (16)−0.0031 (14)
C10.049 (2)0.059 (3)0.049 (3)0.006 (2)0.006 (3)0.006 (3)
O20.0522 (16)0.0618 (18)0.0252 (14)0.0076 (14)0.0057 (15)0.0018 (14)
C20.061 (3)0.057 (2)0.042 (2)0.009 (2)0.018 (2)0.000 (2)
N20.065 (2)0.081 (3)0.056 (3)−0.017 (2)0.022 (3)0.002 (2)
O30.0598 (18)0.0526 (16)0.0528 (18)0.0025 (14)0.0263 (18)−0.0127 (17)
C30.043 (2)0.044 (2)0.027 (2)0.0000 (17)0.003 (2)−0.0032 (19)
C40.0313 (18)0.0400 (19)0.0276 (18)0.0043 (16)0.0004 (19)−0.003 (2)
C50.054 (2)0.038 (2)0.038 (2)0.0027 (18)0.009 (2)0.000 (2)
C60.055 (2)0.042 (2)0.042 (2)0.003 (2)0.006 (2)0.010 (2)
C70.040 (2)0.039 (2)0.034 (2)0.0055 (16)0.009 (2)−0.004 (2)
C80.0340 (18)0.041 (2)0.033 (2)0.0011 (16)0.001 (2)−0.002 (2)
C90.037 (2)0.043 (2)0.034 (2)−0.0003 (18)0.003 (2)0.001 (2)
C100.039 (2)0.046 (2)0.038 (2)0.0061 (18)0.001 (2)−0.004 (2)
C110.053 (2)0.042 (2)0.050 (3)−0.0047 (17)0.008 (3)0.004 (3)
C120.041 (2)0.052 (2)0.043 (3)−0.0045 (19)0.005 (2)0.000 (2)

Geometric parameters (Å, °)

N1—C41.353 (5)C4—C71.359 (5)
N1—C101.390 (5)C5—C61.523 (6)
N1—C51.472 (4)C5—H5A0.9700
O1—C31.408 (5)C5—H5B0.9700
O1—C11.421 (5)C6—H6A0.9700
C1—C21.510 (7)C6—H6B0.9700
C1—H1A0.9700C7—C81.413 (5)
C1—H1B0.9700C7—H7A0.9300
O2—C31.413 (5)C8—C91.379 (6)
O2—C21.419 (5)C8—C111.488 (5)
C2—H2A0.9700C9—C121.432 (6)
C2—H2B0.9700C9—C101.433 (5)
N2—C121.140 (5)C11—H11A0.9600
O3—C101.235 (5)C11—H11B0.9600
C3—C61.504 (6)C11—H11C0.9600
C3—C41.517 (6)
C4—N1—C10124.3 (3)N1—C5—H5B111.2
C4—N1—C5112.8 (3)C6—C5—H5B111.2
C10—N1—C5122.8 (3)H5A—C5—H5B109.1
C3—O1—C1106.8 (3)C3—C6—C5104.3 (3)
O1—C1—C2103.7 (4)C3—C6—H6A110.9
O1—C1—H1A111.0C5—C6—H6A110.9
C2—C1—H1A111.0C3—C6—H6B110.9
O1—C1—H1B111.0C5—C6—H6B110.9
C2—C1—H1B111.0H6A—C6—H6B108.9
H1A—C1—H1B109.0C4—C7—C8119.5 (4)
C3—O2—C2108.2 (3)C4—C7—H7A120.3
O2—C2—C1105.6 (4)C8—C7—H7A120.3
O2—C2—H2A110.6C9—C8—C7117.9 (3)
C1—C2—H2A110.6C9—C8—C11122.3 (4)
O2—C2—H2B110.6C7—C8—C11119.9 (4)
C1—C2—H2B110.6C8—C9—C12120.1 (3)
H2A—C2—H2B108.8C8—C9—C10123.9 (4)
O1—C3—O2105.9 (3)C12—C9—C10116.0 (4)
O1—C3—C6110.4 (3)O3—C10—N1120.6 (3)
O2—C3—C6114.5 (4)O3—C10—C9126.2 (4)
O1—C3—C4109.9 (3)N1—C10—C9113.2 (3)
O2—C3—C4112.9 (3)C8—C11—H11A109.5
C6—C3—C4103.2 (3)C8—C11—H11B109.5
N1—C4—C7121.1 (4)H11A—C11—H11B109.5
N1—C4—C3107.8 (3)C8—C11—H11C109.5
C7—C4—C3131.1 (4)H11A—C11—H11C109.5
N1—C5—C6102.7 (3)H11B—C11—H11C109.5
N1—C5—H5A111.2N2—C12—C9178.3 (5)
C6—C5—H5A111.2
C3—O1—C1—C228.0 (4)O1—C3—C6—C5−87.6 (4)
C3—O2—C2—C1−5.9 (5)O2—C3—C6—C5153.0 (3)
O1—C1—C2—O2−13.4 (5)C4—C3—C6—C529.8 (4)
C1—O1—C3—O2−32.5 (4)N1—C5—C6—C3−27.3 (4)
C1—O1—C3—C6−157.0 (4)N1—C4—C7—C8−3.0 (6)
C1—O1—C3—C489.8 (4)C3—C4—C7—C8174.6 (4)
C2—O2—C3—O123.4 (4)C4—C7—C8—C9−0.6 (6)
C2—O2—C3—C6145.3 (3)C4—C7—C8—C11178.8 (4)
C2—O2—C3—C4−96.9 (4)C7—C8—C9—C12−177.3 (4)
C10—N1—C4—C75.3 (6)C11—C8—C9—C123.3 (6)
C5—N1—C4—C7−177.6 (4)C7—C8—C9—C102.3 (6)
C10—N1—C4—C3−172.8 (3)C11—C8—C9—C10−177.1 (4)
C5—N1—C4—C34.3 (5)C4—N1—C10—O3177.2 (4)
O1—C3—C4—N196.2 (4)C5—N1—C10—O30.4 (6)
O2—C3—C4—N1−145.8 (3)C4—N1—C10—C9−3.5 (6)
C6—C3—C4—N1−21.6 (4)C5—N1—C10—C9179.8 (3)
O1—C3—C4—C7−81.7 (5)C8—C9—C10—O3179.0 (4)
O2—C3—C4—C736.3 (6)C12—C9—C10—O3−1.5 (6)
C6—C3—C4—C7160.5 (4)C8—C9—C10—N1−0.4 (6)
C4—N1—C5—C614.6 (4)C12—C9—C10—N1179.2 (3)
C10—N1—C5—C6−168.3 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C5—H5B···O3i0.972.493.275 (5)138

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HB5573).

References

  • Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.
  • Enraf–Nonius (1994). CAD-4 EXPRESS Enraf–Nonius, Delft, The Netherlands.
  • Harms, K. & Wocadlo, S. (1995). XCAD4 University of Marburg, Germany.
  • North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Takimoto, C. H. & Calvo, E. (2008). Principles of Oncologic Pharmacotherapy. In Cancer Management: A Multidisciplinary Approach, 11 ed., edited by R. Pazdur, L. D. Wagman, K. A.Camphausen & W. J. Hoskins. New York: Cmp United Business Media.
  • Wani, M. C., Ronman, P. E., Lindley, J. T. & Wall, M. E. (1980). J. Med. Chem.23, 554–560. [PubMed]

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