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organic compounds
9,10-Dihydroxy-4,4-dimethyl-5,8-dihydroanthracen-1(4H)-one
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
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
|
Refinement
|
|
Data collection: SMART-NT (Bruker, 2001); cell 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
10.1107/S1600536808010891/hg2395sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536808010891/hg2395Isup2.hkl
The molecule was synthesized by the Diels–Alder reaction between 8,8-dimethylnaphthalene-1,4,5(8H)-trione and butadiene). The
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.The hydrogen atoms positions were calculated after each cycle of
with SHELXL (Bruker,1999) using a riding model for each structure, with C—H distances in the range 0.95 to 0.99 Å and O—H equal to 0.84 Å. Uiso(H) values were set equal to 1.5Ueq of the parent carbon atom for methyl groups and hydroxyl hydrogen atoms, while 1.2Ueq for the others.Data collection: SMART-NT (Bruker, 2001); cell
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).C16H16O3 | F(000) = 544 |
Mr = 256.29 | Dx = 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 |
Siemens SMART CCD area-detector diffractometer | 1198 independent reflections |
Radiation source: fine-focus sealed tube | 948 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.043 |
ϕ and ω scans | θmax = 25.0°, θmin = 2.1° |
Absorption correction: multi-scan (SADABS in SAINT-NT; Bruker, 1999) | h = −10→10 |
Tmin = 0.961, Tmax = 0.993 | k = −9→9 |
7422 measured reflections | l = −22→22 |
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(Fo2) + (0.0796P)2] where P = (Fo2 + 2Fc2)/3 |
1198 reflections | (Δ/σ)max < 0.001 |
112 parameters | Δρmax = 0.33 e Å−3 |
0 restraints | Δρmin = −0.29 e Å−3 |
C16H16O3 | V = 1260.69 (14) Å3 |
Mr = 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 |
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) |
Tmin = 0.961, Tmax = 0.993 | Rint = 0.043 |
7422 measured reflections |
R[F2 > 2σ(F2)] = 0.044 | 0 restraints |
wR(F2) = 0.118 | H-atom parameters constrained |
S = 1.01 | Δρmax = 0.33 e Å−3 |
1198 reflections | Δρmin = −0.29 e Å−3 |
112 parameters |
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. |
x | y | z | Uiso*/Ueq | 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) |
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 |
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. |
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 |
Mr | 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) |
Tmin, Tmax | 0.961, 0.993 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 7422, 1198, 948 |
Rint | 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 |
Δρmax, Δρmin (e Å−3) | 0.33, −0.29 |
Computer programs: SMART-NT (Bruker, 2001), SAINT-NT (Bruker, 1999), SHELXTL-NT (Sheldrick, 2008).
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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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
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.