9,10-Dihydr­oxy-4,4-dimethyl-5,8-dihydro­anthracen-1(4H)-one

Ramírez-Rodríguez, O.; Martínez-Cifuentes, M.; Ibañez, A.; Vega, A.; Araya-Maturana, R.

doi:10.1107/S1600536808010891

organic compounds

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ISSN: 2056-9890

Volume 64| Part 7| July 2008| Page o1316

doi:10.1107/S1600536808010891

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9,10-Dihydroxy-4,4-dimethyl-5,8-dihydroanthracen-1(4H)-one

Oney Ramírez-Rodríguez,^a Maximiliano Martínez-Cifuentes,^a Andres Ibañez,^b Andrés Vega ^c and Ramiro Araya-Maturana ^a ^*

^aDepartamento de Química Orgánica, Facultad de Ciencias Químicas y Farmaceúticas, Universidad de Chile, Casilla 233, Santiago, Chile, ^bCentro de Investigación Interdisciplinaria Avanzada en Ciencia de los Materiales, CIMAT, Universidad de Chile, Santiago, Chile, and ^cLaboratorio de Recursos Naturales, Departamento de Ciencias Químicas, Facultad de Ecología y Recursos Naturales, Universidad Andrés Bello, Av. República 275, Santiago, Chile
^*Correspondence e-mail: raraya@uchile.cl

(Received 16 April 2008; accepted 18 April 2008; online 21 June 2008)

In the title molecule, C₁₆H₁₆O₃, the ring system is planar and an intramolecular hydrogen bond is present. The molecular packing is dominated by an intermolecular hydrogen bond and by π-stacking interactions [interplanar separation 3.8012 Å].

Related literature

For related literature, see: Allen (2002 ); Araya-Maturana et al. (2006 , 2007 ); Desiraju (2002 ); Joshi et al. (1997 ); Valderrama et al. (1993 ).

Experimental

Crystal data

C₁₆H₁₆O₃
M_r = 256.29
Orthorhombic, P n m a
a = 8.5944 (5) Å
b = 7.6024 (5) Å
c = 19.2949 (12) Å
V = 1260.69 (14) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 150 (2) K
0.43 × 0.38 × 0.08 mm

Data collection

Siemens SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS in SAINT-NT; Bruker, 1999 ) T_min = 0.961, T_max = 0.993
7422 measured reflections
1198 independent reflections
948 reflections with I > 2σ(I)
R_int = 0.043

Refinement

R[F² > 2σ(F²)] = 0.044
wR(F²) = 0.118
S = 1.01
1198 reflections
112 parameters
H-atom parameters constrained
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.29 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O1	0.84	1.77	2.5172 (18)	147
O3—H3⋯O1ⁱ	0.84	2.03	2.8022 (18)	152
Symmetry code: (i) x-1, y, z.

Data collection: SMART-NT (Bruker, 2001 ); cell refinement: SAINT-NT (Bruker, 1999); data reduction: SAINT-NT; program(s) used to solve structure: SHELXTL-NT (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL-NT; molecular graphics: SHELXTL-NT; software used to prepare material for publication: SHELXTL-NT.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808010891/hg2395sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808010891/hg2395Isup2.hkl

checkCIF report

Comment top

The title hydroquinone I is a potent antioxidant (Araya-Maturana et al, 2007) and respiration inhibitor of cancer cells (Araya-Maturana et al., 2006). In mouse mammary adenocarcinoma TA3 and their multidrug-resistant variant TA3-MTX-R lines exhibit IC₅₀ values below 10^-4M. Moreover, this compound inhibits the growth of the human tumor U937 cell line at low micromolar concentrations (Araya-Maturana et al., 2006).

The molecule consists of three six-membered carbon rings fused trough atoms 4a, 9a in a side and trough carbons 8a, 10a in the other, to give rise an anthracene skeleton, substituted with an oxo, a gem-dimethyl and two hydroxyl groups at positions 1, 4, 9 and 10 respectively, as shown in Scheme 1. The central ring is aromatic, and double bonds are also found between carbons 2 - 3 and 6 - 7. This double bonds distribution leads to the core to be strictly planar. In fact, all the carbon atoms in the skeleton lies on the crystallographic mirror plane m from space group Pnma. The same happens with the oxo oxygen atom O1 and the hydroxyl groups O2 and O3. Interestingly, the hydroxyl hydrogen atoms H2 and H3 display a trans correlation. The planarity of the molecule together with the proximity of the oxo oxygen atom (O1) and the hydroxyl hydrogen atom (H2) leads to the presence of an intramolecular O—H···O hydrogen bond with O···O of 2.5172 (18) Å, suggesting a rather strong bond (Desiraju, 2002), which is present still in CDCl₃ solution, as indicated by NMR (Araya-Maturana et al, 2007). Few structures with this or some closely related pattern of substitution could be found in Cambridge Structural database (v 5.29, Allen, 2002), being 1,4-Dihydro-9,10-anthrahydroquinone the best, probably the one to the best of our knowledge, example (Joshi et al., 1997).

The molecular packing is also dominated by the hydrogen bond, this time between vicinal molecules. As depicted in Figure 2, a planar chain is produced by means of the interacion of the "terminal" hydroxyl hydrogen atom H3 with the oxo oxygen O1 from the nearest molecule (x - 1, y, z), in a "head to tail" arrangement in the [100] direction. The O···O distance, 2.8022 (18) Å, suggest a weaker interaction. Layers of molecules are defined in the packing by putting this chains one together the other, with no strong interaction between them. Any of the chain is contained in the x, 1/4, z plane. The next layer, x, 3/4, z is separated from the first in b/2, 3.8012 Å, a typical value for the aromatic π-stacking interaction.

Related literature top

For related literature, see: Allen (2002); Araya-Maturana et al. (2006, 2007); Desiraju (2002); Joshi et al. (1997); Valderrama et al. (1993).

Experimental top

The molecule was synthesized by the Diels–Alder reaction between 8,8-dimethylnaphthalene-1,4,5(8H)-trione and butadiene). The cycloaddition takes place exclusively at external quinone doble bond affording the corresponding adduct I-a (See Scheme 2). Enolization of the adduct I-a with silicagel in toluene yield the hydroquinone I. (Valderrama et al., 1993). The ¹H-NMR spectrum in CDCl₃ of I exhibits a sharp singlet at 13.08 p.p.m. indicating that hydrogen bonding is also present in solution. This characteristic is important regarding antitumor and antioxidant properties.

Computing details top

Data collection: SMART-NT (Bruker, 2001); cell refinement: SAINT-NT (Bruker, 1999); data reduction: SAINT-NT (Bruker, 1999); program(s) used to solve structure: SHELXTL-NT (Sheldrick, 2008); program(s) used to refine structure: SHELXTL-NT (Sheldrick, 2008); molecular graphics: SHELXTL-NT (Sheldrick, 2008); software used to prepare material for publication: SHELXTL-NT (Sheldrick, 2008).

Figures top

	Fig. 1. Molecular structure diagramas for I showing atom numbering scheme. Displacement ellipsoids are at 33% probability level and H atoms are shown as spheres of arbitrary radii. Letter a corresponds to the names of fused carbon atoms according to the nomenclature rules. Letter B to symmcode x, -y + 1/2, z.
	Fig. 2. Molecular packing view for I along [010]. [symmetry codes: (B) x + 1, y, z; (C) x - 1, y, z].
	Fig. 3. The formation of the title compound.

9,10-Dihydroxy-4,4-dimethyl-5,8-dihydroanthracen-1(4H)-one top

Crystal data top

C₁₆H₁₆O₃	F(000) = 544
M_r = 256.29	D_x = 1.350 Mg m⁻³
Orthorhombic, Pnma	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2n	Cell parameters from 2361 reflections
a = 8.5944 (5) Å	θ = 2.6–25.0°
b = 7.6024 (5) Å	µ = 0.09 mm⁻¹
c = 19.2949 (12) Å	T = 150 K
V = 1260.69 (14) Å³	Plate, orange
Z = 4	0.43 × 0.38 × 0.08 mm

Data collection top

Siemens SMART CCD area-detector diffractometer	1198 independent reflections
Radiation source: fine-focus sealed tube	948 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.043
ϕ and ω scans	θ_max = 25.0°, θ_min = 2.1°
Absorption correction: multi-scan (SADABS in SAINT-NT; Bruker, 1999)	h = −10→10
T_min = 0.961, T_max = 0.993	k = −9→9
7422 measured reflections	l = −22→22

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)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.118	H-atom parameters constrained
S = 1.01	w = 1/[σ²(F_o²) + (0.0796P)²] where P = (F_o² + 2F_c²)/3
1198 reflections	(Δ/σ)_max < 0.001
112 parameters	Δρ_max = 0.33 e Å⁻³
0 restraints	Δρ_min = −0.29 e Å⁻³

Crystal data top

C₁₆H₁₆O₃	V = 1260.69 (14) Å³
M_r = 256.29	Z = 4
Orthorhombic, Pnma	Mo Kα radiation
a = 8.5944 (5) Å	µ = 0.09 mm⁻¹
b = 7.6024 (5) Å	T = 150 K
c = 19.2949 (12) Å	0.43 × 0.38 × 0.08 mm

Data collection top

Siemens SMART CCD area-detector diffractometer	1198 independent reflections
Absorption correction: multi-scan (SADABS in SAINT-NT; Bruker, 1999)	948 reflections with I > 2σ(I)
T_min = 0.961, T_max = 0.993	R_int = 0.043
7422 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.044	0 restraints
wR(F²) = 0.118	H-atom parameters constrained
S = 1.01	Δρ_max = 0.33 e Å⁻³
1198 reflections	Δρ_min = −0.29 e Å⁻³
112 parameters

Special details top

Experimental. 10 s by frame separated by 0.3 °

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) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
O1	1.23661 (15)	0.2500	0.97450 (7)	0.0430 (4)
C1	1.1134 (2)	0.2500	0.93987 (9)	0.0316 (5)
C2	1.1204 (2)	0.2500	0.86508 (10)	0.0394 (5)
H2B	1.2188	0.2500	0.8427	0.047*
C3	0.9915 (2)	0.2500	0.82719 (10)	0.0366 (5)
H3A	1.0040	0.2500	0.7783	0.044*
C4	0.8283 (2)	0.2500	0.85428 (9)	0.0276 (5)
C11	0.74913 (15)	0.41540 (18)	0.82447 (7)	0.0319 (4)
H11A	0.7543	0.4123	0.7737	0.048*
H11B	0.8027	0.5206	0.8415	0.048*
H11C	0.6400	0.4184	0.8392	0.048*
C4A	0.8227 (2)	0.2500	0.93365 (10)	0.0250 (4)
C10	0.68158 (19)	0.2500	0.96919 (10)	0.0257 (5)
O3	0.54736 (14)	0.2500	0.93053 (6)	0.0349 (4)
H3	0.4700	0.2500	0.9571	0.052*
C10A	0.67531 (19)	0.2500	1.04249 (9)	0.0246 (5)
C5	0.5186 (2)	0.2500	1.07767 (10)	0.0293 (5)
H5A	0.4600	0.3551	1.0623	0.035*	0.50
H5B	0.4600	0.1449	1.0623	0.035*	0.50
C6	0.5260 (2)	0.2500	1.15519 (10)	0.0302 (5)
H6A	0.4305	0.2500	1.1800	0.036*
C7	0.6566 (2)	0.2500	1.19124 (10)	0.0299 (5)
H7A	0.6495	0.2500	1.2404	0.036*
C8	0.8143 (2)	0.2500	1.15932 (10)	0.0311 (5)
H8A	0.8718	0.1448	1.1755	0.037*	0.50
H8B	0.8718	0.3552	1.1755	0.037*	0.50
C8A	0.8116 (2)	0.2500	1.08099 (9)	0.0252 (4)
C9	0.9537 (2)	0.2500	1.04619 (9)	0.0257 (5)
O2	1.08404 (15)	0.2500	1.08586 (6)	0.0356 (4)
H2	1.1629	0.2500	1.0602	0.053*
C9A	0.9614 (2)	0.2500	0.97343 (10)	0.0255 (5)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0199 (7)	0.0740 (12)	0.0351 (8)	0.000	−0.0021 (6)	0.000
C1	0.0210 (10)	0.0430 (12)	0.0310 (11)	0.000	−0.0009 (8)	0.000
C2	0.0246 (10)	0.0629 (14)	0.0306 (12)	0.000	0.0075 (9)	0.000
C3	0.0322 (11)	0.0527 (13)	0.0248 (10)	0.000	0.0037 (8)	0.000
C4	0.0232 (9)	0.0384 (12)	0.0213 (10)	0.000	−0.0015 (7)	0.000
C11	0.0346 (8)	0.0375 (8)	0.0237 (7)	−0.0025 (6)	−0.0025 (5)	0.0023 (6)
C4A	0.0230 (10)	0.0287 (10)	0.0232 (10)	0.000	−0.0008 (7)	0.000
C10	0.0211 (10)	0.0313 (11)	0.0246 (10)	0.000	−0.0020 (7)	0.000
O3	0.0189 (7)	0.0610 (10)	0.0247 (7)	0.000	−0.0024 (5)	0.000
C10A	0.0243 (10)	0.0264 (10)	0.0233 (10)	0.000	0.0004 (7)	0.000
C5	0.0226 (10)	0.0377 (11)	0.0276 (11)	0.000	0.0003 (7)	0.000
C6	0.0286 (10)	0.0335 (11)	0.0286 (10)	0.000	0.0069 (8)	0.000
C7	0.0354 (11)	0.0323 (11)	0.0221 (10)	0.000	0.0021 (8)	0.000
C8	0.0291 (10)	0.0395 (12)	0.0247 (10)	0.000	−0.0036 (8)	0.000
C8A	0.0262 (10)	0.0261 (10)	0.0233 (10)	0.000	−0.0012 (7)	0.000
C9	0.0222 (9)	0.0307 (11)	0.0243 (10)	0.000	−0.0039 (7)	0.000
O2	0.0215 (7)	0.0583 (9)	0.0271 (8)	0.000	−0.0058 (6)	0.000
C9A	0.0225 (10)	0.0291 (10)	0.0248 (10)	0.000	−0.0008 (7)	0.000

Geometric parameters (Å, º) top

O1—C1	1.252 (2)	O3—H3	0.8400
C1—C2	1.444 (3)	C10A—C8A	1.387 (2)
C1—C9A	1.458 (2)	C10A—C5	1.508 (2)
C2—C3	1.327 (3)	C5—C6	1.497 (3)
C2—H2B	0.9500	C5—H5A	0.9900
C3—C4	1.497 (2)	C5—H5B	0.9900
C3—H3A	0.9500	C6—C7	1.320 (3)
C4—C4A	1.532 (3)	C6—H6A	0.9500
C4—C11ⁱ	1.5410 (16)	C7—C8	1.489 (3)
C4—C11	1.5410 (16)	C7—H7A	0.9500
C11—H11A	0.9800	C8—C8A	1.512 (3)
C11—H11B	0.9800	C8—H8A	0.9900
C11—H11C	0.9800	C8—H8B	0.9900
C4A—C10	1.393 (2)	C8A—C9	1.394 (2)
C4A—C9A	1.418 (2)	C9—O2	1.357 (2)
C10—O3	1.374 (2)	C9—C9A	1.405 (3)
C10—C10A	1.415 (3)	O2—H2	0.8400

O1—C1—C2	119.87 (16)	C10—C10A—C5	118.94 (16)
O1—C1—C9A	121.38 (17)	C6—C5—C10A	114.34 (15)
C2—C1—C9A	118.75 (16)	C6—C5—H5A	108.7
C3—C2—C1	121.05 (17)	C10A—C5—H5A	108.7
C3—C2—H2B	119.5	C6—C5—H5B	108.7
C1—C2—H2B	119.5	C10A—C5—H5B	108.7
C2—C3—C4	126.13 (18)	H5A—C5—H5B	107.6
C2—C3—H3A	116.9	C7—C6—C5	124.20 (17)
C4—C3—H3A	116.9	C7—C6—H6A	117.9
C3—C4—C4A	112.24 (15)	C5—C6—H6A	117.9
C3—C4—C11ⁱ	106.46 (10)	C6—C7—C8	123.79 (17)
C4A—C4—C11ⁱ	111.05 (10)	C6—C7—H7A	118.1
C3—C4—C11	106.46 (10)	C8—C7—H7A	118.1
C4A—C4—C11	111.05 (10)	C7—C8—C8A	113.53 (15)
C11ⁱ—C4—C11	109.37 (14)	C7—C8—H8A	108.9
C4—C11—H11A	109.5	C8A—C8—H8A	108.9
C4—C11—H11B	109.5	C7—C8—H8B	108.9
H11A—C11—H11B	109.5	C8A—C8—H8B	108.9
C4—C11—H11C	109.5	H8A—C8—H8B	107.7
H11A—C11—H11C	109.5	C10A—C8A—C9	118.81 (17)
H11B—C11—H11C	109.5	C10A—C8A—C8	123.28 (16)
C10—C4A—C9A	117.74 (17)	C9—C8A—C8	117.91 (15)
C10—C4A—C4	121.29 (15)	O2—C9—C8A	116.85 (16)
C9A—C4A—C4	120.97 (15)	O2—C9—C9A	121.64 (16)
O3—C10—C4A	117.62 (16)	C8A—C9—C9A	121.50 (16)
O3—C10—C10A	120.71 (15)	C9—O2—H2	109.5
C4A—C10—C10A	121.67 (16)	C9—C9A—C4A	120.08 (16)
C10—O3—H3	109.5	C9—C9A—C1	119.07 (16)
C8A—C10A—C10	120.20 (16)	C4A—C9A—C1	120.86 (16)
C8A—C10A—C5	120.86 (17)

C2—C3—C4—C11	121.70 (9)	C11—C4—C4A—C9A	−119.04 (10)
C11—C4—C4A—C10	60.96 (10)

Symmetry code: (i) x, −y+1/2, z.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O1	0.84	1.77	2.5172 (18)	147
O3—H3···O1ⁱⁱ	0.84	2.03	2.8022 (18)	152

Symmetry code: (ii) x−1, y, z.

Experimental details

Crystal data
Chemical formula	C₁₆H₁₆O₃
M_r	256.29
Crystal system, space group	Orthorhombic, Pnma
Temperature (K)	150
a, b, c (Å)	8.5944 (5), 7.6024 (5), 19.2949 (12)
V (Å³)	1260.69 (14)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.43 × 0.38 × 0.08

Data collection
Diffractometer	Siemens SMART CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS in SAINT-NT; Bruker, 1999)
T_min, T_max	0.961, 0.993
No. of measured, independent and observed [I > 2σ(I)] reflections	7422, 1198, 948
R_int	0.043
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.118, 1.01
No. of reflections	1198
No. of parameters	112
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.33, −0.29

Computer programs: SMART-NT (Bruker, 2001), SAINT-NT (Bruker, 1999), SHELXTL-NT (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O1	0.84	1.77	2.5172 (18)	147.2
O3—H3···O1ⁱ	0.84	2.03	2.8022 (18)	151.9

Symmetry code: (i) x−1, y, z.

Acknowledgements

This work was supported by FONDECYT grant 1071077.

References

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