5,8-Dimethyl-3-methyl­ene-2-oxo-3,3a,4,5,5a,6,8a,8b-octa­hydro-2H-1-oxa-s-indacene-5-carbaldehyde

Moumou, M.; Benharref, A.; Berraho, M.; Daran, J.-C.; Akssira, M.; Elhakmaoui, A.

doi:10.1107/S1600536811018344

organic compounds

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ISSN: 2056-9890

Volume 67| Part 6| June 2011| Page o1479

doi:10.1107/S1600536811018344

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5,8-Dimethyl-3-methylene-2-oxo-3,3a,4,5,5a,6,8a,8b-octahydro-2H-1-oxa-s-indacene-5-carbaldehyde

Mohamed Moumou,^a ^* Ahmed Benharref,^b Moha Berraho,^b Jean-Claude Daran,^c Mohamed Akssira ^a and Ahmed Elhakmaoui ^a

^aLaboratoire de Chimie Bioorganique et Analytique, URAC 22, BP 146, FSTM, Université Hassan II, Mohammedia-Casablanca 20810 Mohammedia, Morocco, ^bLaboratoire de Chimie des Substances Naturelles, URAC16, Faculté des Sciences Semlalia, BP 2390 Bd My Abdellah, 40000 Marrakech, Morocco, and ^cLaboratoire de Chimie de Coordination, 205 route de Narbonne, 31077 Toulouse Cedex 04, France
^*Correspondence e-mail: mmoumou17@yahoo.fr

(Received 12 May 2011; accepted 14 May 2011; online 20 May 2011)

The title compound, C₁₅H₁₈O₃, was synthesized from 9α-hydroxyparthenolide (9α-hydroxy-4,8-dimethyl-12-methylene-3,14-dioxatricyclo[9.3.0.0^2,4]tetradec-7-en-13-one), which was isolated from the chloroform extract of the aerial parts of Anvillea radiata. The five-membered lactone ring has a twisted conformation, while the six- and five-membered rings display chair and envelope conformations, respectively. The dihedral angle between the two five-membered rings is 50.57 (11)°.

Related literature

For the isolation and biological activity of 9α-hydroxyparthenolide, see: Abdel Sattar et al. (1996 ); El Hassany et al. (2004 ). For the reactivity of this sesquiterpene, see: Castaneda-Acosta et al. (1993 ); Neukirch et al. (2003 ); Der-Ren et al. (2006 ); Neelakantan et al. (2009 ). For conformational analysis, see: Cremer & Pople (1975 ).

Experimental

Crystal data

C₁₅H₁₈O₃
M_r = 246.29
Orthorhombic, P 2₁ 2₁ 2₁
a = 9.5293 (3) Å
b = 9.7885 (3) Å
c = 13.7524 (4) Å
V = 1282.79 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 173 K
0.50 × 0.33 × 0.08 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
22932 measured reflections
1517 independent reflections
1403 reflections with I > 2σ(I)
R_int = 0.026

Refinement

R[F² > 2σ(F²)] = 0.031
wR(F²) = 0.085
S = 1.09
1517 reflections
165 parameters
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ); cell refinement: APEX2 and SAINT (Bruker, 2005); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811018344/sj5146sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811018344/sj5146Isup2.hkl

checkCIF report

Comment top

The natural sesquiterpene lactone (9α - hydroxypartenolide) is the main constituent of the chloroform extract of aerial parts of Anvillea radiata (El Hassany et al., 2004) and of Anvillea garcini (Abdel Sattar et al., 1996). The reactivity of this sesquiterpene lactone and its derivatives has been the subject of several studies (Castaneda-Acosta et al. 1993; Neukirch et al., 2003; Der-Ren et al., 2006; Neelakantan et al., 2009), in order to prepare products with high added value for use in industrial pharmacology. In the same context, we have treated the 9α-hydroxyparthenolide with boron trifluoride etherate and obtained the 5,8-diméthyl-3-methylen-2-oxo-3,3a,4,5,5a,6,8a,8b- octahydro-2H-1-oxa-as-indacene-5-carbaldehyde 64% yield. The structure of this new sesquiterpene derivative of 9α - hydroxypartenolide was determined by ¹H and ¹³C NMR spectral analysis and mass spectrometry, and was confirmed by its single crystal X-ray structure. The molecule contains three fused rings which exhibit different conformations. The molecular structure of (I), Fig.1, shows the lactone ring to adopt a twisted conformation, as indicated by Cremer & Pople (1975) puckering parameters Q = 0.3329 (18) Å and ϕ = 304.4 (3)°. The five-membered ring displays an envelope conformation with Q = 0.340 (2)Å and ϕ = 356.8 (3)°, while the six-membered ring has a chair conformation with QT = 0.5707 (18) Å, θ = 16.39 (18)°, ϕ = 333.5 (7)°.

Related literature top

For the isolation and biological activity of 9α-hydroxyparthenolide, see: Abdel Sattar et al. (1996); El Hassany et al. (2004). For the reactivity of this sesquiterpene, see: Castaneda-Acosta et al. (1993); Neukirch et al. (2003); Der-Ren et al. (2006); Neelakantan et al. (2009). For conformational analysis, see: Cremer & Pople (1975).

Experimental top

Boron trifluoride etherate (1 ml, freshly distilled under reduced pressure) was added via syringe over a 10 minute period to a stirred solution of 500 mg (1.89 mmol) of the 9α-hydroxyparthenolide in anhydrous benzene (20 ml), cooled in an ice-bath and maintained under a N₂ atmosphere. The ice-bath was then removed and stirring was continued for 2 h during which time the solution became cloudy and reddish in colour. The reaction mixture was poured into cooled water and dichloromethane. After shaking, the layers were separated; the organic layer was treated three time with saturated sodium bicarbonate (3x30ml), dried over sodium sulfate and concentrated under reduced pressure. Chromatography of the residue obtained on silica gel with hexane/ ethyl acetate (85/15) as eluent allowed us to isolate in pure 300 mg (1.21 mmol) of 5,8-dimethyl-3-methylene - 2-oxo-3,3a,4,5,5a,6,8a,8 b –octahydro-2H-1-oxa-as-indacene-5-carbaldehyde. The title compound was recrystallized from ethyl acetate.

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: APEX2 and SAINT (Bruker, 2005); data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

Fig. 1. : Molecular structure of the title compound with the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are represented as small spheres of arbitrary radii.

5,8-Dimethyl-3-methylene-2-oxo-3,3a,4,5,5a,6,8a,8b-octahydro- 2H-1-oxa-s-indacene-5-carbaldehyde top

Crystal data top

C₁₅H₁₈O₃	F(000) = 528
M_r = 246.29	D_x = 1.275 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 22932 reflections
a = 9.5293 (3) Å	θ = 2.6–26.4°
b = 9.7885 (3) Å	µ = 0.09 mm⁻¹
c = 13.7524 (4) Å	T = 173 K
V = 1282.79 (7) Å³	Platelet, colourless
Z = 4	0.50 × 0.33 × 0.08 mm

Data collection top

Bruker APEXII CCD area-detector diffractometer	1403 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.026
Graphite monochromator	θ_max = 26.4°, θ_min = 2.6°
ϕ and ω scans	h = −9→11
22932 measured reflections	k = −12→12
1517 independent reflections	l = −17→17

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.031	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.085	H-atom parameters constrained
S = 1.09	w = 1/[σ²(F_o²) + (0.0511P)² + 0.1837P] where P = (F_o² + 2F_c²)/3
1517 reflections	(Δ/σ)_max < 0.001
165 parameters	Δρ_max = 0.18 e Å⁻³
0 restraints	Δρ_min = −0.16 e Å⁻³

Crystal data top

C₁₅H₁₈O₃	V = 1282.79 (7) Å³
M_r = 246.29	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 9.5293 (3) Å	µ = 0.09 mm⁻¹
b = 9.7885 (3) Å	T = 173 K
c = 13.7524 (4) Å	0.50 × 0.33 × 0.08 mm

Data collection top

Bruker APEXII CCD area-detector diffractometer	1403 reflections with I > 2σ(I)
22932 measured reflections	R_int = 0.026
1517 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.031	0 restraints
wR(F²) = 0.085	H-atom parameters constrained
S = 1.09	Δρ_max = 0.18 e Å⁻³
1517 reflections	Δρ_min = −0.16 e Å⁻³
165 parameters

Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C2	−0.05168 (19)	0.3323 (2)	0.83535 (13)	0.0323 (4)
C3	−0.01615 (19)	0.47821 (19)	0.85677 (12)	0.0307 (4)
C3A	0.12071 (17)	0.47296 (17)	0.91013 (12)	0.0267 (4)
H3	0.0996	0.4573	0.9790	0.032*
C4	0.22933 (18)	0.58577 (18)	0.90494 (13)	0.0301 (4)
H4A	0.1903	0.6701	0.9303	0.036*
H4B	0.2568	0.6010	0.8379	0.036*
C5	0.3576 (2)	0.54344 (18)	0.96536 (13)	0.0311 (4)
C5A	0.40893 (18)	0.39541 (18)	0.94628 (13)	0.0288 (4)
H5A	0.4649	0.3698	1.0032	0.035*
C6	0.5034 (2)	0.3693 (2)	0.85704 (15)	0.0382 (5)
H6A	0.4700	0.4183	0.8003	0.046*
H6B	0.6000	0.3950	0.8699	0.046*
C7	0.4886 (2)	0.2173 (2)	0.84457 (14)	0.0377 (4)
H7	0.5514	0.1638	0.8095	0.045*
C8	0.3756 (2)	0.16819 (18)	0.88923 (12)	0.0321 (4)
C8A	0.29432 (17)	0.28351 (16)	0.93605 (11)	0.0254 (3)
H8A	0.2558	0.2568	0.9993	0.030*
C8B	0.18260 (17)	0.34167 (17)	0.86986 (12)	0.0252 (3)
H8B	0.2253	0.3615	0.8066	0.030*
C9	−0.0975 (2)	0.5818 (2)	0.83263 (14)	0.0386 (4)
H9A	−0.1819	0.5660	0.8006	0.046*
H9B	−0.0705	0.6706	0.8477	0.046*
C10	0.3226 (2)	0.55169 (19)	1.07397 (14)	0.0379 (4)
H10	0.3857	0.5104	1.1164	0.046*
C11	0.4789 (2)	0.6450 (2)	0.95088 (17)	0.0439 (5)
H11A	0.4487	0.7350	0.9691	0.066*
H11B	0.5069	0.6451	0.8838	0.066*
H11C	0.5570	0.6184	0.9907	0.066*
C12	0.3260 (2)	0.02303 (19)	0.89327 (14)	0.0401 (5)
H12A	0.3250	−0.0075	0.9596	0.060*
H12B	0.3882	−0.0337	0.8560	0.060*
H12C	0.2330	0.0173	0.8668	0.060*
O1	0.06185 (12)	0.25263 (13)	0.85447 (9)	0.0302 (3)
O2	−0.16069 (14)	0.28443 (16)	0.80758 (11)	0.0455 (4)
O3	0.22305 (18)	0.60552 (17)	1.10965 (11)	0.0531 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C2	0.0276 (9)	0.0415 (10)	0.0279 (8)	0.0015 (8)	0.0021 (7)	−0.0003 (8)
C3	0.0266 (8)	0.0389 (9)	0.0266 (8)	0.0034 (8)	0.0031 (7)	0.0002 (7)
C3A	0.0255 (8)	0.0299 (8)	0.0249 (7)	0.0042 (7)	0.0017 (7)	0.0012 (7)
C4	0.0310 (9)	0.0268 (8)	0.0324 (8)	0.0032 (8)	−0.0011 (7)	0.0029 (7)
C5	0.0293 (9)	0.0276 (8)	0.0363 (9)	−0.0007 (8)	−0.0049 (7)	0.0014 (7)
C5A	0.0253 (8)	0.0300 (8)	0.0311 (8)	0.0026 (7)	−0.0042 (7)	0.0048 (7)
C6	0.0260 (9)	0.0436 (11)	0.0450 (10)	0.0037 (8)	0.0069 (8)	0.0072 (9)
C7	0.0337 (10)	0.0403 (10)	0.0391 (10)	0.0121 (9)	0.0021 (8)	−0.0002 (8)
C8	0.0370 (9)	0.0315 (8)	0.0277 (8)	0.0087 (8)	−0.0050 (7)	0.0024 (7)
C8A	0.0284 (8)	0.0252 (7)	0.0224 (7)	0.0017 (7)	−0.0006 (6)	0.0031 (6)
C8B	0.0234 (8)	0.0284 (8)	0.0238 (7)	0.0000 (7)	0.0024 (6)	0.0013 (6)
C9	0.0369 (10)	0.0447 (10)	0.0341 (9)	0.0101 (9)	−0.0045 (8)	0.0023 (8)
C10	0.0452 (11)	0.0324 (9)	0.0361 (9)	−0.0010 (9)	−0.0088 (8)	−0.0034 (7)
C11	0.0363 (10)	0.0347 (10)	0.0607 (13)	−0.0060 (9)	−0.0088 (10)	0.0054 (9)
C12	0.0527 (12)	0.0303 (9)	0.0373 (9)	0.0080 (9)	−0.0072 (9)	−0.0012 (8)
O1	0.0274 (6)	0.0322 (6)	0.0310 (6)	−0.0012 (5)	−0.0001 (5)	−0.0018 (5)
O2	0.0287 (7)	0.0547 (9)	0.0530 (8)	−0.0036 (7)	−0.0043 (6)	−0.0080 (7)
O3	0.0599 (10)	0.0579 (9)	0.0414 (8)	0.0095 (9)	0.0002 (7)	−0.0130 (7)

Geometric parameters (Å, º) top

C2—O2	1.202 (2)	C6—H6B	0.9700
C2—O1	1.360 (2)	C7—C8	1.330 (3)
C2—C3	1.497 (3)	C7—H7	0.9300
C3—C9	1.319 (3)	C8—C12	1.499 (3)
C3—C3A	1.497 (2)	C8—C8A	1.513 (2)
C3A—C4	1.515 (2)	C8A—C8B	1.512 (2)
C3A—C8B	1.519 (2)	C8A—H8A	0.9800
C3A—H3	0.9800	C8B—O1	1.459 (2)
C4—C5	1.535 (2)	C8B—H8B	0.9800
C4—H4A	0.9700	C9—H9A	0.9300
C4—H4B	0.9700	C9—H9B	0.9300
C5—C10	1.533 (3)	C10—O3	1.191 (2)
C5—C11	1.538 (3)	C10—H10	0.9300
C5—C5A	1.552 (2)	C11—H11A	0.9600
C5A—C6	1.544 (3)	C11—H11B	0.9600
C5A—C8A	1.553 (2)	C11—H11C	0.9600
C5A—H5A	0.9800	C12—H12A	0.9600
C6—C7	1.504 (3)	C12—H12B	0.9600
C6—H6A	0.9700	C12—H12C	0.9600

O2—C2—O1	121.68 (18)	C8—C7—H7	123.8
O2—C2—C3	129.07 (18)	C6—C7—H7	123.8
O1—C2—C3	109.23 (15)	C7—C8—C12	128.02 (18)
C9—C3—C2	123.43 (17)	C7—C8—C8A	109.96 (16)
C9—C3—C3A	131.43 (18)	C12—C8—C8A	122.00 (16)
C2—C3—C3A	105.12 (14)	C8B—C8A—C8	112.67 (13)
C3—C3A—C4	123.15 (14)	C8B—C8A—C5A	106.51 (13)
C3—C3A—C8B	100.87 (14)	C8—C8A—C5A	101.81 (14)
C4—C3A—C8B	109.53 (13)	C8B—C8A—H8A	111.8
C3—C3A—H3	107.4	C8—C8A—H8A	111.8
C4—C3A—H3	107.4	C5A—C8A—H8A	111.8
C8B—C3A—H3	107.4	O1—C8B—C8A	114.69 (13)
C3A—C4—C5	108.77 (14)	O1—C8B—C3A	104.61 (13)
C3A—C4—H4A	109.9	C8A—C8B—C3A	111.88 (13)
C5—C4—H4A	109.9	O1—C8B—H8B	108.5
C3A—C4—H4B	109.9	C8A—C8B—H8B	108.5
C5—C4—H4B	109.9	C3A—C8B—H8B	108.5
H4A—C4—H4B	108.3	C3—C9—H9A	120.0
C10—C5—C4	109.89 (16)	C3—C9—H9B	120.0
C10—C5—C11	104.81 (16)	H9A—C9—H9B	120.0
C4—C5—C11	110.74 (15)	O3—C10—C5	126.73 (19)
C10—C5—C5A	106.41 (14)	O3—C10—H10	116.6
C4—C5—C5A	114.30 (15)	C5—C10—H10	116.6
C11—C5—C5A	110.18 (15)	C5—C11—H11A	109.5
C6—C5A—C5	118.22 (15)	C5—C11—H11B	109.5
C6—C5A—C8A	102.79 (14)	H11A—C11—H11B	109.5
C5—C5A—C8A	116.89 (14)	C5—C11—H11C	109.5
C6—C5A—H5A	106.0	H11A—C11—H11C	109.5
C5—C5A—H5A	106.0	H11B—C11—H11C	109.5
C8A—C5A—H5A	106.0	C8—C12—H12A	109.5
C7—C6—C5A	101.51 (16)	C8—C12—H12B	109.5
C7—C6—H6A	111.5	H12A—C12—H12B	109.5
C5A—C6—H6A	111.5	C8—C12—H12C	109.5
C7—C6—H6B	111.5	H12A—C12—H12C	109.5
C5A—C6—H6B	111.5	H12B—C12—H12C	109.5
H6A—C6—H6B	109.3	C2—O1—C8B	108.23 (13)
C8—C7—C6	112.41 (18)

Experimental details

Crystal data
Chemical formula	C₁₅H₁₈O₃
M_r	246.29
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	173
a, b, c (Å)	9.5293 (3), 9.7885 (3), 13.7524 (4)
V (Å³)	1282.79 (7)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.50 × 0.33 × 0.08

Data collection
Diffractometer	Bruker APEXII CCD area-detector diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	22932, 1517, 1403
R_int	0.026
(sin θ/λ)_max (Å⁻¹)	0.625

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.031, 0.085, 1.09
No. of reflections	1517
No. of parameters	165
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.16

Computer programs: APEX2 (Bruker, 2005), APEX2 and SAINT (Bruker, 2005), SAINT (Bruker, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).

Acknowledgements

The authors thank the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for the X-ray measurements.

References

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