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

Gomes, R.C.; Simoni, D. de A.; Coelho, F.

doi:10.1107/S2414314616009251

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 1| Part 6| June 2016| x160925

doi:10.1107/S2414314616009251

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

Ralph C. Gomes,^a Deborah de Alencar Simoni ^b and Fernando Coelho ^a ^*

^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].

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 conjugated system, 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).

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), building up head-to-tail chains along [001] (Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

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.

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).

Refinement

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

Table 2
Experimental details

Crystal data
Chemical formula	C₁₇H₁₄O₄
M_r	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)
V (Å³)	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 )
T_min, T_max	0.680, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	30763, 2846, 2638
R_int	0.020
(sin θ/λ)_max (Å⁻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
Δρ_max, Δρ_min (e Å⁻³)	0.49, −0.37
Computer programs: APEX2 and SAINT (Bruker, 2010), SHELXS97 (Sheldrick, 2008 ), SHELXL2014/7 (Sheldrick, 2015 ), Mercury (Macrae et al., 2006 ) and publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 1483988

Crystal structure: contains datablocks I, New_Global_Publ_Block. DOI: 10.1107/S2414314616009251/sj4046sup1.cif

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

checkCIF report

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

C₁₇H₁₄O₄	Z = 2
M_r = 282.28	F(000) = 296
Triclinic, P1	D_x = 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

Data collection top

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	R_int = 0.020
phi and ω scans	θ_max = 26.4°, θ_min = 2.2°
Absorption correction: multi-scan (SADABS; Bruker, 2010)	h = −10→10
T_min = 0.680, T_max = 0.746	k = −11→11
30763 measured reflections	l = −12→12

Refinement top

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(F_o²) + (0.0413P)² + 0.3344P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max < 0.001
2846 reflections	Δρ_max = 0.49 e Å⁻³
191 parameters	Δρ_min = −0.37 e Å⁻³

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

	x	y	z	U_iso*/U_eq
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*

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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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