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ISSN: 2414-3146

Methyl 8-oxo-2-phenyl-1-oxa­spiro­[4.5]deca-2,6,9-triene-3-carboxyl­ate

aLaboratory of Synthesis of Natural Products and Drugs, Institute of Chemistry, University of Campinas, PO Box 6154, 13083-970, Campinas, SP, Brazil, and bLaboratory of Single Crystal X-Ray Diffraction, Institute of Chemistry, University of Campinas, PO Box 6154 - 13083-970, Campinas-SP, Brazil
*Correspondence e-mail: coelho@iqm.unicamp.br

Edited by J. Simpson, University of Otago, New Zealand (Received 4 June 2016; accepted 7 June 2016; online 14 June 2016)

The title compound, C17H14O4, is a 5/6 spiro-ring fused system, where the five- and six-membered rings are inclined to one another by 89.79 (5)° at the spiro-carbon. In the crystal, non-classical C—H ⋯ O hydrogen bonds form inversion dimers and connect the mol­ecules into chains along [001].

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

Compounds with spiro ring systems, when compared to planar aromatic compounds, have greater three-dimensionality and different physical properties. This has been shown to increase their potential effectiveness as drugs (Winkler et al., 2015[Winkler, M., Maynadier, M., Wein, S., Lespinasse, M.-A., Boumis, G., Miele, A. E., Vial, H. & Wong, Y.-S. (2015). Org. Biomol. Chem. 13, 2064-2077.]; Zheng et al., 2014[Zheng, Y., Tice, C. M. & Singh, S. B. (2014). Bioorg. Med. Chem. Lett. 24, 3673-3682.]). The title compound is a 5/6 spiro-ring fused system, in which the six-membered ring is a cyclo­hexa­dienone moiety where the carbonyl group and the two double bonds constitute a highly conjugated system, making it an efficient Michael acceptor. This chemical property is normally associated with biological activity (Pirovani et al., 2009[Pirovani, R. V., Ferreira, B. R. V. & Coelho, F. (2009). Synlett, pp. 2333-2337.]). Good evidence of the pharmacophoric properties of the cyclo­hexa­dienone moiety is the loss of anti­malarial activity of aculeatin A when this group is reduced to the corresponding ketone analogue. Furthermore, construction of an aculeatin A analogue with two spiro­cyclo­hexa­dienone units led to improved anti­malarial potency (Winkler et al., 2015[Winkler, M., Maynadier, M., Wein, S., Lespinasse, M.-A., Boumis, G., Miele, A. E., Vial, H. & Wong, Y.-S. (2015). Org. Biomol. Chem. 13, 2064-2077.]).

In the title compound, Fig. 1[link], the five-membered and the six-membered rings of the spiro system are almost planar, with r.m.s. deviations 0.021 and 0.008 Å, respectively. The hexa­dienone ring is rotated by 89.79 (5)° with respect to the five-membered ring. This is similar to the values found in related 5/6 spiro-ring fused systems containing the cyclo­hexa­dienone moiety that have been reported previously (Lou, 2012[Lou, Y. (2012). Acta Cryst. E68, o1152.]; Martins et al., 2014[Martins, L. J., Simoni, D. de A., Aparicio, R. & Coelho, F. (2014). Acta Cryst. E70, o1275-o1276.]; Rønnest et al., 2011[Rønnest, M. H., Nielsen, M. T., Leber, B., Mortensen, U. H., Krämer, A., Clausen, M. H., Larsen, T. O. & Harris, P. (2011). Acta Cryst. C67, o125-o128.]). The phenyl ring is inclined to the five-membered ring by 35.88 (6)°, while the planar methyl carboxyl­ate substituent, C3/C16/O4/C17, is inclined to this ring by only 6.61 (13)°. The torsion angles C4—C3—C16—O4, 5.93 (17)°, C15—C1—C2—O2, −141.12 (12)°, and C1—C2—C3—C16, 4.3 (2)° are close to those found in an analogous 5/6 spiro-system containing a dibrominated cyclo­hexa­dienone ring (Martins et al., 2014[Martins, L. J., Simoni, D. de A., Aparicio, R. & Coelho, F. (2014). Acta Cryst. E70, o1275-o1276.]).

[Figure 1]
Figure 1
The mol­ecular structure of the title compound with atom labels and 50% probability displacement ellipsoids.

In the crystal, mol­ecules form pairs of inversion dimers via non-classical hydrogen bonds (C4—H4A⋯ O1 and C14—H14⋯O3, Table 1[link]), building up head-to-tail chains along [001] (Fig. 2[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
C4—H4A⋯O1i 0.99 2.58 3.2504 (19) 125
C14—H14⋯O3ii 0.95 2.52 3.3884 (17) 153
Symmetry codes: (i) -x+1, -y, -z+1; (ii) -x+1, -y+1, -z-1.
[Figure 2]
Figure 2
Crystal packing of the title compound, showing the dimers formed by non-classical inter­molecular C—H ⋯ O hydrogen bonds (dashed lines).

Synthesis and crystallization

The title compound was obtained by a synthetic protocol whose first step is the Heck reaction of a Morita–Baylis–Hillman adduct with 4-iodo­phenol, in the presence of a Nájera N-oxime-derived palladacycle as catalyst, to give the corresponding α-aryl-β-keto ester (83% yield for the isolated and purified product). Next, the α-aryl-β-keto ester was treated with [bis­(tri­fluoro­acet­oxy)iodo]­benzene, in anhydrous aceto­nitrile, to furnish the desired spiro-hexa­dienone (75% yield for the isolated and purified product). The compound was re-dissolved in di­chloro­methane and light-yellow block-like crystals were obtained by slow evaporation of the solvent at room temperature. For a detailed description of this synthesis, see Pirovani et al. (2009[Pirovani, R. V., Ferreira, B. R. V. & Coelho, F. (2009). Synlett, pp. 2333-2337.]).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link].

Table 2
Experimental details

Crystal data
Chemical formula C17H14O4
Mr 282.28
Crystal system, space group Triclinic, P[\overline{1}]
Temperature (K) 150
a, b, c (Å) 8.0416 (8), 9.4577 (10), 9.7397 (10)
α, β, γ (°) 74.168 (2), 84.636 (2), 78.731 (2)
V3) 698.28 (12)
Z 2
Radiation type Mo Kα
μ (mm−1) 0.10
Crystal size (mm) 0.37 × 0.21 × 0.21
 
Data collection
Diffractometer Bruker APEX CCD detector
Absorption correction Multi-scan (SADABS; Bruker, 2010[Bruker (2010). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.680, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections 30763, 2846, 2638
Rint 0.020
(sin θ/λ)max−1) 0.625
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.039, 0.099, 1.05
No. of reflections 2846
No. of parameters 191
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.49, −0.37
Computer programs: APEX2 and SAINT (Bruker, 2010[Bruker (2010). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2014/7 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]), Mercury (Macrae et al., 2006[Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453-457.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Structural data


Computing details top

Data collection: APEX2 (Bruker, 2010); cell refinement: SAINT (Bruker, 2010); data reduction: SAINT (Bruker, 2010); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2006); software used to prepare material for publication: publCIF (Westrip, 2010).

Methyl 8-oxo-2-phenyl-1-oxaspiro[4.5]deca-2,6,9-triene-3-carboxylate top
Crystal data top
C17H14O4Z = 2
Mr = 282.28F(000) = 296
Triclinic, P1Dx = 1.343 Mg m3
a = 8.0416 (8) ÅMo Kα radiation, λ = 0.71073 Å
b = 9.4577 (10) ÅCell parameters from 93 reflections
c = 9.7397 (10) Åθ = 3.3–26.7°
α = 74.168 (2)°µ = 0.10 mm1
β = 84.636 (2)°T = 150 K
γ = 78.731 (2)°Block, light yellow
V = 698.28 (12) Å30.37 × 0.21 × 0.21 mm
Data collection top
Bruker APEX CCD detector
diffractometer
2846 independent reflections
Radiation source: fine-focus sealed tube2638 reflections with I > 2σ(I)
Detector resolution: 8.3333 pixels mm-1Rint = 0.020
phi and ω scansθmax = 26.4°, θmin = 2.2°
Absorption correction: multi-scan
(SADABS; Bruker, 2010)
h = 1010
Tmin = 0.680, Tmax = 0.746k = 1111
30763 measured reflectionsl = 1212
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.039H-atom parameters constrained
wR(F2) = 0.099 w = 1/[σ2(Fo2) + (0.0413P)2 + 0.3344P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max < 0.001
2846 reflectionsΔρmax = 0.49 e Å3
191 parametersΔρmin = 0.37 e Å3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.18597 (17)0.00818 (15)0.58977 (12)0.0594 (4)
O20.30998 (11)0.27812 (11)0.07753 (10)0.0320 (2)
O30.72621 (12)0.36813 (12)0.23114 (10)0.0381 (3)
O40.86312 (11)0.18240 (10)0.06200 (10)0.0300 (2)
C10.32385 (15)0.43009 (13)0.15731 (13)0.0220 (3)
C20.41536 (15)0.32065 (13)0.03849 (13)0.0225 (3)
C30.57777 (16)0.25242 (13)0.01880 (13)0.0233 (3)
C40.59324 (17)0.14561 (17)0.12760 (15)0.0360 (3)
H4A0.67560.16940.18360.043*
H4B0.62840.04110.12170.043*
C50.41077 (16)0.17208 (14)0.19365 (13)0.0266 (3)
C60.39846 (19)0.24628 (15)0.31205 (16)0.0339 (3)
H60.44110.33670.29500.041*
C70.3303 (2)0.19091 (17)0.44045 (15)0.0380 (3)
H70.32930.24110.51280.046*
C80.25653 (18)0.05505 (17)0.47397 (14)0.0357 (3)
C90.26682 (18)0.02037 (15)0.36014 (16)0.0349 (3)
H90.22420.11090.37850.042*
C100.33392 (18)0.03464 (15)0.23263 (14)0.0311 (3)
H100.33320.01650.16120.037*
C110.18775 (17)0.53458 (14)0.12597 (14)0.0285 (3)
H110.15960.53700.02960.034*
C120.09371 (18)0.63454 (16)0.23470 (17)0.0371 (3)
H120.00260.70690.21310.045*
C130.13212 (18)0.62930 (17)0.37493 (16)0.0382 (3)
H130.06640.69730.44930.046*
C140.26596 (18)0.52542 (16)0.40708 (14)0.0325 (3)
H140.29180.52210.50350.039*
C150.36248 (16)0.42623 (14)0.29899 (13)0.0255 (3)
H150.45500.35560.32140.031*
C160.72412 (15)0.27742 (13)0.11712 (13)0.0231 (3)
C171.01867 (17)0.19418 (18)0.14803 (17)0.0376 (3)
H17A1.02010.14520.22490.056*
H17B1.11580.14560.08810.056*
H17C1.02560.29970.18940.056*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0608 (8)0.0683 (8)0.0271 (6)0.0076 (6)0.0145 (5)0.0055 (5)
O20.0230 (5)0.0425 (6)0.0217 (5)0.0041 (4)0.0019 (3)0.0043 (4)
O30.0268 (5)0.0483 (6)0.0291 (5)0.0070 (4)0.0014 (4)0.0063 (4)
O40.0217 (4)0.0317 (5)0.0320 (5)0.0012 (4)0.0011 (4)0.0042 (4)
C10.0210 (6)0.0215 (6)0.0236 (6)0.0075 (4)0.0007 (4)0.0034 (5)
C20.0247 (6)0.0241 (6)0.0197 (6)0.0085 (5)0.0019 (5)0.0056 (5)
C30.0251 (6)0.0235 (6)0.0204 (6)0.0055 (5)0.0011 (5)0.0037 (5)
C40.0268 (7)0.0433 (8)0.0266 (7)0.0026 (6)0.0010 (5)0.0063 (6)
C50.0275 (6)0.0291 (6)0.0199 (6)0.0058 (5)0.0012 (5)0.0001 (5)
C60.0392 (8)0.0260 (6)0.0391 (8)0.0070 (6)0.0107 (6)0.0087 (6)
C70.0470 (8)0.0408 (8)0.0276 (7)0.0060 (6)0.0102 (6)0.0184 (6)
C80.0345 (7)0.0388 (8)0.0217 (7)0.0071 (6)0.0022 (5)0.0014 (6)
C90.0366 (7)0.0278 (7)0.0370 (8)0.0099 (6)0.0035 (6)0.0019 (6)
C100.0373 (7)0.0309 (7)0.0289 (7)0.0091 (6)0.0003 (5)0.0124 (5)
C110.0281 (6)0.0276 (6)0.0292 (7)0.0053 (5)0.0027 (5)0.0070 (5)
C120.0297 (7)0.0294 (7)0.0439 (8)0.0022 (5)0.0013 (6)0.0018 (6)
C130.0316 (7)0.0358 (7)0.0360 (8)0.0031 (6)0.0066 (6)0.0090 (6)
C140.0323 (7)0.0388 (7)0.0235 (6)0.0099 (6)0.0019 (5)0.0004 (5)
C150.0243 (6)0.0277 (6)0.0242 (6)0.0062 (5)0.0003 (5)0.0056 (5)
C160.0230 (6)0.0244 (6)0.0234 (6)0.0058 (5)0.0014 (5)0.0076 (5)
C170.0214 (6)0.0457 (8)0.0436 (8)0.0038 (6)0.0040 (6)0.0113 (7)
Geometric parameters (Å, º) top
O1—C81.2233 (17)C7—C81.463 (2)
O2—C21.3649 (14)C7—H70.9500
O2—C51.4753 (15)C8—C91.462 (2)
O3—C161.2049 (16)C9—C101.3176 (19)
O4—C161.3422 (15)C9—H90.9500
O4—C171.4445 (16)C10—H100.9500
C1—C151.3947 (17)C11—C121.382 (2)
C1—C111.3954 (18)C11—H110.9500
C1—C21.4697 (17)C12—C131.384 (2)
C2—C31.3450 (18)C12—H120.9500
C3—C161.4603 (17)C13—C141.383 (2)
C3—C41.5058 (17)C13—H130.9500
C4—C51.5484 (18)C14—C151.3857 (18)
C4—H4A0.9900C14—H140.9500
C4—H4B0.9900C15—H150.9500
C5—C101.4889 (18)C17—H17A0.9800
C5—C61.4916 (19)C17—H17B0.9800
C6—C71.329 (2)C17—H17C0.9800
C6—H60.9500
C2—O2—C5109.13 (9)C9—C8—C7116.56 (12)
C16—O4—C17116.00 (10)C10—C9—C8121.37 (13)
C15—C1—C11119.37 (11)C10—C9—H9119.3
C15—C1—C2121.86 (11)C8—C9—H9119.3
C11—C1—C2118.65 (11)C9—C10—C5123.96 (12)
C3—C2—O2113.21 (11)C9—C10—H10118.0
C3—C2—C1134.71 (11)C5—C10—H10118.0
O2—C2—C1112.08 (10)C12—C11—C1120.20 (12)
C2—C3—C16127.59 (11)C12—C11—H11119.9
C2—C3—C4109.82 (11)C1—C11—H11119.9
C16—C3—C4122.55 (11)C11—C12—C13120.06 (13)
C3—C4—C5102.63 (11)C11—C12—H12120.0
C3—C4—H4A111.2C13—C12—H12120.0
C5—C4—H4A111.2C14—C13—C12120.20 (13)
C3—C4—H4B111.2C14—C13—H13119.9
C5—C4—H4B111.2C12—C13—H13119.9
H4A—C4—H4B109.2C13—C14—C15120.14 (13)
O2—C5—C10106.01 (10)C13—C14—H14119.9
O2—C5—C6106.60 (10)C15—C14—H14119.9
C10—C5—C6113.32 (11)C14—C15—C1120.01 (12)
O2—C5—C4104.99 (9)C14—C15—H15120.0
C10—C5—C4112.35 (12)C1—C15—H15120.0
C6—C5—C4112.79 (12)O3—C16—O4123.01 (11)
C7—C6—C5122.59 (13)O3—C16—C3127.24 (12)
C7—C6—H6118.7O4—C16—C3109.75 (10)
C5—C6—H6118.7O4—C17—H17A109.5
C6—C7—C8122.11 (13)O4—C17—H17B109.5
C6—C7—H7118.9H17A—C17—H17B109.5
C8—C7—H7118.9O4—C17—H17C109.5
O1—C8—C9121.24 (15)H17A—C17—H17C109.5
O1—C8—C7122.17 (15)H17B—C17—H17C109.5
C5—O2—C2—C32.26 (14)C6—C7—C8—O1176.17 (15)
C5—O2—C2—C1178.33 (10)C6—C7—C8—C92.1 (2)
C15—C1—C2—C338.1 (2)O1—C8—C9—C10175.99 (15)
C11—C1—C2—C3145.95 (14)C7—C8—C9—C102.3 (2)
C15—C1—C2—O2141.12 (12)C8—C9—C10—C52.6 (2)
C11—C1—C2—O234.81 (15)O2—C5—C10—C9118.93 (15)
O2—C2—C3—C16176.46 (11)C6—C5—C10—C92.3 (2)
C1—C2—C3—C164.3 (2)C4—C5—C10—C9126.94 (15)
O2—C2—C3—C41.02 (15)C15—C1—C11—C120.87 (19)
C1—C2—C3—C4178.22 (13)C2—C1—C11—C12176.89 (12)
C2—C3—C4—C53.59 (15)C1—C11—C12—C131.3 (2)
C16—C3—C4—C5174.03 (11)C11—C12—C13—C140.8 (2)
C2—O2—C5—C10123.48 (11)C12—C13—C14—C150.1 (2)
C2—O2—C5—C6115.50 (11)C13—C14—C15—C10.6 (2)
C2—O2—C5—C44.38 (14)C11—C1—C15—C140.08 (18)
C3—C4—C5—O24.65 (14)C2—C1—C15—C14175.81 (11)
C3—C4—C5—C10119.40 (12)C17—O4—C16—O30.14 (18)
C3—C4—C5—C6111.02 (13)C17—O4—C16—C3179.99 (11)
O2—C5—C6—C7118.32 (14)C2—C3—C16—O33.3 (2)
C10—C5—C6—C72.09 (19)C4—C3—C16—O3173.93 (14)
C4—C5—C6—C7126.98 (15)C2—C3—C16—O4176.89 (12)
C5—C6—C7—C82.1 (2)C4—C3—C16—O45.93 (17)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H4A···O1i0.992.583.2504 (19)125
C14—H14···O3ii0.952.523.3884 (17)153
Symmetry codes: (i) x+1, y, z+1; (ii) x+1, y+1, z1.
 

Acknowledgements

The authors are grateful to the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP 2009/51602–5 and 2013/07600–5) for financial support and to the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq 140751/2014–9) for a fellowship for RCG.

References

First citationBruker (2010). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationLou, Y. (2012). Acta Cryst. E68, o1152.  CSD CrossRef IUCr Journals Google Scholar
First citationMacrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
First citationMartins, L. J., Simoni, D. de A., Aparicio, R. & Coelho, F. (2014). Acta Cryst. E70, o1275–o1276.  CSD CrossRef IUCr Journals Google Scholar
First citationPirovani, R. V., Ferreira, B. R. V. & Coelho, F. (2009). Synlett, pp. 2333–2337.  Google Scholar
First citationRønnest, M. H., Nielsen, M. T., Leber, B., Mortensen, U. H., Krämer, A., Clausen, M. H., Larsen, T. O. & Harris, P. (2011). Acta Cryst. C67, o125–o128.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationWestrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationWinkler, M., Maynadier, M., Wein, S., Lespinasse, M.-A., Boumis, G., Miele, A. E., Vial, H. & Wong, Y.-S. (2015). Org. Biomol. Chem. 13, 2064–2077.  Web of Science CrossRef CAS PubMed Google Scholar
First citationZheng, Y., Tice, C. M. & Singh, S. B. (2014). Bioorg. Med. Chem. Lett. 24, 3673–3682.  Web of Science CrossRef CAS PubMed Google Scholar

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