organic compounds
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
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].
Keywords: crystal structure; spiro-cyclohexadienone; Morita–Baylis–Hillman adducts; hydrogen bonds.
CCDC reference: 1483988
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; Zheng et al., 2014). 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 making it an efficient Michael acceptor. This chemical property is normally associated with biological activity (Pirovani et al., 2009). 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).
In the title compound, Fig. 1, 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; Martins et al., 2014; Rønnest et al., 2011). 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).
In the crystal, molecules form pairs of inversion dimers via non-classical hydrogen bonds (C4—H4A⋯ O1 and C14—H14⋯O3, Table 1), building up head-to-tail chains along [001] (Fig. 2).
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).
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 1483988
10.1107/S2414314616009251/sj4046sup1.cif
contains datablocks I, New_Global_Publ_Block. DOI:Structure factors: contains datablock I. DOI: 10.1107/S2414314616009251/sj4046Isup2.hkl
Supporting information file. DOI: 10.1107/S2414314616009251/sj4046Isup3.ps
Supporting information file. DOI: 10.1107/S2414314616009251/sj4046Isup4.cdx
Supporting information file. DOI: 10.1107/S2414314616009251/sj4046Isup5.cml
Data collection: APEX2 (Bruker, 2010); cell
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).C17H14O4 | Z = 2 |
Mr = 282.28 | F(000) = 296 |
Triclinic, P1 | Dx = 1.343 Mg m−3 |
a = 8.0416 (8) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 9.4577 (10) Å | Cell parameters from 93 reflections |
c = 9.7397 (10) Å | θ = 3.3–26.7° |
α = 74.168 (2)° | µ = 0.10 mm−1 |
β = 84.636 (2)° | T = 150 K |
γ = 78.731 (2)° | Block, light yellow |
V = 698.28 (12) Å3 | 0.37 × 0.21 × 0.21 mm |
Bruker APEX CCD detector diffractometer | 2846 independent reflections |
Radiation source: fine-focus sealed tube | 2638 reflections with I > 2σ(I) |
Detector resolution: 8.3333 pixels mm-1 | Rint = 0.020 |
phi and ω scans | θmax = 26.4°, θmin = 2.2° |
Absorption correction: multi-scan (SADABS; Bruker, 2010) | h = −10→10 |
Tmin = 0.680, Tmax = 0.746 | k = −11→11 |
30763 measured reflections | l = −12→12 |
Refinement on F2 | 0 restraints |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.039 | H-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 reflections | Δρmax = 0.49 e Å−3 |
191 parameters | Δρmin = −0.37 e Å−3 |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.18597 (17) | 0.00818 (15) | 0.58977 (12) | 0.0594 (4) | |
O2 | 0.30998 (11) | 0.27812 (11) | 0.07753 (10) | 0.0320 (2) | |
O3 | 0.72621 (12) | 0.36813 (12) | −0.23114 (10) | 0.0381 (3) | |
O4 | 0.86312 (11) | 0.18240 (10) | −0.06200 (10) | 0.0300 (2) | |
C1 | 0.32385 (15) | 0.43009 (13) | −0.15731 (13) | 0.0220 (3) | |
C2 | 0.41536 (15) | 0.32065 (13) | −0.03849 (13) | 0.0225 (3) | |
C3 | 0.57777 (16) | 0.25242 (13) | −0.01880 (13) | 0.0233 (3) | |
C4 | 0.59324 (17) | 0.14561 (17) | 0.12760 (15) | 0.0360 (3) | |
H4A | 0.6756 | 0.1694 | 0.1836 | 0.043* | |
H4B | 0.6284 | 0.0411 | 0.1217 | 0.043* | |
C5 | 0.41077 (16) | 0.17208 (14) | 0.19365 (13) | 0.0266 (3) | |
C6 | 0.39846 (19) | 0.24628 (15) | 0.31205 (16) | 0.0339 (3) | |
H6 | 0.4411 | 0.3367 | 0.2950 | 0.041* | |
C7 | 0.3303 (2) | 0.19091 (17) | 0.44045 (15) | 0.0380 (3) | |
H7 | 0.3293 | 0.2411 | 0.5128 | 0.046* | |
C8 | 0.25653 (18) | 0.05505 (17) | 0.47397 (14) | 0.0357 (3) | |
C9 | 0.26682 (18) | −0.02037 (15) | 0.36014 (16) | 0.0349 (3) | |
H9 | 0.2242 | −0.1109 | 0.3785 | 0.042* | |
C10 | 0.33392 (18) | 0.03464 (15) | 0.23263 (14) | 0.0311 (3) | |
H10 | 0.3332 | −0.0165 | 0.1612 | 0.037* | |
C11 | 0.18775 (17) | 0.53458 (14) | −0.12597 (14) | 0.0285 (3) | |
H11 | 0.1596 | 0.5370 | −0.0296 | 0.034* | |
C12 | 0.09371 (18) | 0.63454 (16) | −0.23470 (17) | 0.0371 (3) | |
H12 | 0.0026 | 0.7069 | −0.2131 | 0.045* | |
C13 | 0.13212 (18) | 0.62930 (17) | −0.37493 (16) | 0.0382 (3) | |
H13 | 0.0664 | 0.6973 | −0.4493 | 0.046* | |
C14 | 0.26596 (18) | 0.52542 (16) | −0.40708 (14) | 0.0325 (3) | |
H14 | 0.2918 | 0.5221 | −0.5035 | 0.039* | |
C15 | 0.36248 (16) | 0.42623 (14) | −0.29899 (13) | 0.0255 (3) | |
H15 | 0.4550 | 0.3556 | −0.3214 | 0.031* | |
C16 | 0.72412 (15) | 0.27742 (13) | −0.11712 (13) | 0.0231 (3) | |
C17 | 1.01867 (17) | 0.19418 (18) | −0.14803 (17) | 0.0376 (3) | |
H17A | 1.0201 | 0.1452 | −0.2249 | 0.056* | |
H17B | 1.1158 | 0.1456 | −0.0881 | 0.056* | |
H17C | 1.0256 | 0.2997 | −0.1894 | 0.056* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0608 (8) | 0.0683 (8) | 0.0271 (6) | 0.0076 (6) | 0.0145 (5) | 0.0055 (5) |
O2 | 0.0230 (5) | 0.0425 (6) | 0.0217 (5) | −0.0041 (4) | 0.0019 (3) | 0.0043 (4) |
O3 | 0.0268 (5) | 0.0483 (6) | 0.0291 (5) | −0.0070 (4) | 0.0014 (4) | 0.0063 (4) |
O4 | 0.0217 (4) | 0.0317 (5) | 0.0320 (5) | −0.0012 (4) | 0.0011 (4) | −0.0042 (4) |
C1 | 0.0210 (6) | 0.0215 (6) | 0.0236 (6) | −0.0075 (4) | −0.0007 (4) | −0.0034 (5) |
C2 | 0.0247 (6) | 0.0241 (6) | 0.0197 (6) | −0.0085 (5) | 0.0019 (5) | −0.0056 (5) |
C3 | 0.0251 (6) | 0.0235 (6) | 0.0204 (6) | −0.0055 (5) | −0.0011 (5) | −0.0037 (5) |
C4 | 0.0268 (7) | 0.0433 (8) | 0.0266 (7) | −0.0026 (6) | 0.0010 (5) | 0.0063 (6) |
C5 | 0.0275 (6) | 0.0291 (6) | 0.0199 (6) | −0.0058 (5) | −0.0012 (5) | −0.0001 (5) |
C6 | 0.0392 (8) | 0.0260 (6) | 0.0391 (8) | −0.0070 (6) | −0.0107 (6) | −0.0087 (6) |
C7 | 0.0470 (8) | 0.0408 (8) | 0.0276 (7) | 0.0060 (6) | −0.0102 (6) | −0.0184 (6) |
C8 | 0.0345 (7) | 0.0388 (8) | 0.0217 (7) | 0.0071 (6) | 0.0022 (5) | 0.0014 (6) |
C9 | 0.0366 (7) | 0.0278 (7) | 0.0370 (8) | −0.0099 (6) | 0.0035 (6) | −0.0019 (6) |
C10 | 0.0373 (7) | 0.0309 (7) | 0.0289 (7) | −0.0091 (6) | 0.0003 (5) | −0.0124 (5) |
C11 | 0.0281 (6) | 0.0276 (6) | 0.0292 (7) | −0.0053 (5) | 0.0027 (5) | −0.0070 (5) |
C12 | 0.0297 (7) | 0.0294 (7) | 0.0439 (8) | 0.0022 (5) | 0.0013 (6) | −0.0018 (6) |
C13 | 0.0316 (7) | 0.0358 (7) | 0.0360 (8) | −0.0031 (6) | −0.0066 (6) | 0.0090 (6) |
C14 | 0.0323 (7) | 0.0388 (7) | 0.0235 (6) | −0.0099 (6) | −0.0019 (5) | −0.0004 (5) |
C15 | 0.0243 (6) | 0.0277 (6) | 0.0242 (6) | −0.0062 (5) | 0.0003 (5) | −0.0056 (5) |
C16 | 0.0230 (6) | 0.0244 (6) | 0.0234 (6) | −0.0058 (5) | −0.0014 (5) | −0.0076 (5) |
C17 | 0.0214 (6) | 0.0457 (8) | 0.0436 (8) | −0.0038 (6) | 0.0040 (6) | −0.0113 (7) |
O1—C8 | 1.2233 (17) | C7—C8 | 1.463 (2) |
O2—C2 | 1.3649 (14) | C7—H7 | 0.9500 |
O2—C5 | 1.4753 (15) | C8—C9 | 1.462 (2) |
O3—C16 | 1.2049 (16) | C9—C10 | 1.3176 (19) |
O4—C16 | 1.3422 (15) | C9—H9 | 0.9500 |
O4—C17 | 1.4445 (16) | C10—H10 | 0.9500 |
C1—C15 | 1.3947 (17) | C11—C12 | 1.382 (2) |
C1—C11 | 1.3954 (18) | C11—H11 | 0.9500 |
C1—C2 | 1.4697 (17) | C12—C13 | 1.384 (2) |
C2—C3 | 1.3450 (18) | C12—H12 | 0.9500 |
C3—C16 | 1.4603 (17) | C13—C14 | 1.383 (2) |
C3—C4 | 1.5058 (17) | C13—H13 | 0.9500 |
C4—C5 | 1.5484 (18) | C14—C15 | 1.3857 (18) |
C4—H4A | 0.9900 | C14—H14 | 0.9500 |
C4—H4B | 0.9900 | C15—H15 | 0.9500 |
C5—C10 | 1.4889 (18) | C17—H17A | 0.9800 |
C5—C6 | 1.4916 (19) | C17—H17B | 0.9800 |
C6—C7 | 1.329 (2) | C17—H17C | 0.9800 |
C6—H6 | 0.9500 | ||
C2—O2—C5 | 109.13 (9) | C9—C8—C7 | 116.56 (12) |
C16—O4—C17 | 116.00 (10) | C10—C9—C8 | 121.37 (13) |
C15—C1—C11 | 119.37 (11) | C10—C9—H9 | 119.3 |
C15—C1—C2 | 121.86 (11) | C8—C9—H9 | 119.3 |
C11—C1—C2 | 118.65 (11) | C9—C10—C5 | 123.96 (12) |
C3—C2—O2 | 113.21 (11) | C9—C10—H10 | 118.0 |
C3—C2—C1 | 134.71 (11) | C5—C10—H10 | 118.0 |
O2—C2—C1 | 112.08 (10) | C12—C11—C1 | 120.20 (12) |
C2—C3—C16 | 127.59 (11) | C12—C11—H11 | 119.9 |
C2—C3—C4 | 109.82 (11) | C1—C11—H11 | 119.9 |
C16—C3—C4 | 122.55 (11) | C11—C12—C13 | 120.06 (13) |
C3—C4—C5 | 102.63 (11) | C11—C12—H12 | 120.0 |
C3—C4—H4A | 111.2 | C13—C12—H12 | 120.0 |
C5—C4—H4A | 111.2 | C14—C13—C12 | 120.20 (13) |
C3—C4—H4B | 111.2 | C14—C13—H13 | 119.9 |
C5—C4—H4B | 111.2 | C12—C13—H13 | 119.9 |
H4A—C4—H4B | 109.2 | C13—C14—C15 | 120.14 (13) |
O2—C5—C10 | 106.01 (10) | C13—C14—H14 | 119.9 |
O2—C5—C6 | 106.60 (10) | C15—C14—H14 | 119.9 |
C10—C5—C6 | 113.32 (11) | C14—C15—C1 | 120.01 (12) |
O2—C5—C4 | 104.99 (9) | C14—C15—H15 | 120.0 |
C10—C5—C4 | 112.35 (12) | C1—C15—H15 | 120.0 |
C6—C5—C4 | 112.79 (12) | O3—C16—O4 | 123.01 (11) |
C7—C6—C5 | 122.59 (13) | O3—C16—C3 | 127.24 (12) |
C7—C6—H6 | 118.7 | O4—C16—C3 | 109.75 (10) |
C5—C6—H6 | 118.7 | O4—C17—H17A | 109.5 |
C6—C7—C8 | 122.11 (13) | O4—C17—H17B | 109.5 |
C6—C7—H7 | 118.9 | H17A—C17—H17B | 109.5 |
C8—C7—H7 | 118.9 | O4—C17—H17C | 109.5 |
O1—C8—C9 | 121.24 (15) | H17A—C17—H17C | 109.5 |
O1—C8—C7 | 122.17 (15) | H17B—C17—H17C | 109.5 |
C5—O2—C2—C3 | 2.26 (14) | C6—C7—C8—O1 | −176.17 (15) |
C5—O2—C2—C1 | −178.33 (10) | C6—C7—C8—C9 | 2.1 (2) |
C15—C1—C2—C3 | 38.1 (2) | O1—C8—C9—C10 | 175.99 (15) |
C11—C1—C2—C3 | −145.95 (14) | C7—C8—C9—C10 | −2.3 (2) |
C15—C1—C2—O2 | −141.12 (12) | C8—C9—C10—C5 | 2.6 (2) |
C11—C1—C2—O2 | 34.81 (15) | O2—C5—C10—C9 | −118.93 (15) |
O2—C2—C3—C16 | −176.46 (11) | C6—C5—C10—C9 | −2.3 (2) |
C1—C2—C3—C16 | 4.3 (2) | C4—C5—C10—C9 | 126.94 (15) |
O2—C2—C3—C4 | 1.02 (15) | C15—C1—C11—C12 | −0.87 (19) |
C1—C2—C3—C4 | −178.22 (13) | C2—C1—C11—C12 | −176.89 (12) |
C2—C3—C4—C5 | −3.59 (15) | C1—C11—C12—C13 | 1.3 (2) |
C16—C3—C4—C5 | 174.03 (11) | C11—C12—C13—C14 | −0.8 (2) |
C2—O2—C5—C10 | −123.48 (11) | C12—C13—C14—C15 | −0.1 (2) |
C2—O2—C5—C6 | 115.50 (11) | C13—C14—C15—C1 | 0.6 (2) |
C2—O2—C5—C4 | −4.38 (14) | C11—C1—C15—C14 | −0.08 (18) |
C3—C4—C5—O2 | 4.65 (14) | C2—C1—C15—C14 | 175.81 (11) |
C3—C4—C5—C10 | 119.40 (12) | C17—O4—C16—O3 | −0.14 (18) |
C3—C4—C5—C6 | −111.02 (13) | C17—O4—C16—C3 | 179.99 (11) |
O2—C5—C6—C7 | 118.32 (14) | C2—C3—C16—O3 | 3.3 (2) |
C10—C5—C6—C7 | 2.09 (19) | C4—C3—C16—O3 | −173.93 (14) |
C4—C5—C6—C7 | −126.98 (15) | C2—C3—C16—O4 | −176.89 (12) |
C5—C6—C7—C8 | −2.1 (2) | C4—C3—C16—O4 | 5.93 (17) |
D—H···A | D—H | H···A | D···A | 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. |
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.
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