organic compounds
of 1-(2,4-dihydroxy-6-methylphenyl)ethanone
aDepartment of Chemistry, and Center for Excellence in Protein Structure and Function, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
*Correspondence e-mail: palangpon.kon@mahidol.ac.th
The title compound, C9H10O3, is a bioactive secondary metabolite, isolated from the endophytic fungus Nodulisporium sp. The compound exhibits an intramolecular O—H⋯O hydrogen bond between the phenolic H atom and the carbonyl O atom of the adjacent acetyl group. In the crystal, molecules are linked by hydrogen bonds involving the 4-phenolic H atom and a symmetry-related carbonyl O atom of a neighboring molecule, resulting in extended supramolecular chains along the a-axis direction. Aromatic π–π stacking interactions between the nearly parallel benzene rings of adjacent chains [centroid–centroid distance = 3.7478 (8) Å] further stabilize the three-dimensional supramolecular framework.
Keywords: crystal structure; 1-(2,4-dihydroxy-6-methylphenyl)ethanone; bioactive secondary metabolite; hydrogen bonding; π–π stacking.
CCDC reference: 1412605
1. Related literature
For biological activities of acetophenone derivatives, see: Das & Khosla (2009); Suzuki et al. (2006); Tabuchi et al. (2014). For related structures, see: Azeezaa et al. (2009); Chakkaravarthi et al. (2007); Hill et al. (2012).
2. Experimental
2.1. Crystal data
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2.2. Data collection
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2.3. Refinement
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Data collection: COLLECT (Nonius, 2000); cell SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO (Otwinowski & Minor, 1997) and SCALEPACK; program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015); molecular graphics: OLEX2 (Dolomanov et al., 2009) and Mercury (Macrae et al., 2008); software used to prepare material for publication: publCIF (Westrip, 2010).
Supporting information
CCDC reference: 1412605
https://doi.org/10.1107/S2056989015013468/xu5859sup1.cif
contains datablocks I, New_Global_Publ_Block. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989015013468/xu5859Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989015013468/xu5859Isup3.cml
The title compound C9H10O3 (Fig. 1), 2,4-dihydroxy-6-methylacetophenone [systematic name: 1-(2,4-dihydroxy-6-methylphenyl) ethanone], was a pentaketide secondary metabolite isolated from the culture media of the endophytic fungus Nodulisporium sp. Derivatives of this acetophenone have been demonstrated to possess interesting pharmacological activities, such as inhibition of lettuce seeds (Tabuchi et al., 2014), bacterial plasmid transfer inhibition (Das and Khosla, 2009) and anticancer activity (Suzuki et al., 2006). It is an important biosynthesis precursor for a large varieties of bioactive polyketides.
The geometric parameters of this compound (Fig. 2) are comparable with previously reported values of similar acetophenone compounds (Azeezaa et al., 2009; Chakkaravarthi et al., 2007a; Hill et al., 2012). The bond lengths of C7—C8 and C6—C12 (1.4970 (2) and 1.5050 (2) Å), longer than that of C1—C7 (1.4580 (2) Å), may be a result of a resonant effect between C7—O9 (1.2485 (18) Å) carbonyl group and the aromatic ring. The bond length of C2—O10 (1.3466 (18) Å) is shorter than C4—O11 (1.3573 (19) Å). This may be a result of O10 being involved in an intramolecular hydrogen bond. The acetyl group is coplanar with the aromatic ring C2—C1—C7—O9 (dihedral angle of 7.2 (2) °). The torsion angles C7—C1—C6—C12 and C7—C1—C6—C5 [1.9 (2)° and -179.75 (13)°, respectively] indicate a planar conformation of the respective moieties. An intramolecular hydrogen bond was observed between the 2-phenolic hydrogen to the carbonyl group, O10—H10···O9 (D—H···A= 2.4983 (16) Å and O—H···O = 145°) to hold a carbonyl functionality in the coplanar plane of the aromatic ring. Intermolecular hydrogen bonds between the 4-hydroxyl group to the carbonyl oxygen O11—H11···O9 (D—H···A= 2.7862 (18) Å and O—H···O = 171°) link the molecules in to an extended polymeric structure (Fig. 1). The π···π stacking intermolecular interactions between two aromatic rings (centriod C1—C6) with a distance of (3.7478 (8) Å) (Fig. 2), further stabilize the three-dimensional network.
The culture media of the endophytic fungus Nodolisporium sp. (10 L) were extracted with EtOAc (6 x 500 mL). After removal of the solvent under reduced pressure, the EtOAc extract (2.25 g) was subjected to
over silica gel eluting with EtOAc:hexane (30-100%), followed by MeOH:EtOAc (0-100%) to yield fractions 1-19. After combination and removal of the solvents, fraction 4 (162.9 mg) was further purified by Sephadex LH-20 (20% H2O-MeOH) to yield 2,4-dihydroxy-6-methylacetophenone (133 mg). Single crystals were obtained by slow evaporation from EtOAc solution.The methyl H atoms were constrained to an ideal geometry with C—H distances of 0.98 Å and each group was allowed to rotate freely about its C—C bond. All other hydrogen atoms were placed in idealized locations (C—H = 0.96–0.98 Å, O—H = 0.82 Å) and refined as riding with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(O, methyl C).
The title compound C9H10O3 (Fig. 1), 2,4-dihydroxy-6-methylacetophenone [systematic name: 1-(2,4-dihydroxy-6-methylphenyl) ethanone], was a pentaketide secondary metabolite isolated from the culture media of the endophytic fungus Nodulisporium sp. Derivatives of this acetophenone have been demonstrated to possess interesting pharmacological activities, such as inhibition of lettuce seeds (Tabuchi et al., 2014), bacterial plasmid transfer inhibition (Das and Khosla, 2009) and anticancer activity (Suzuki et al., 2006). It is an important biosynthesis precursor for a large varieties of bioactive polyketides.
The geometric parameters of this compound (Fig. 2) are comparable with previously reported values of similar acetophenone compounds (Azeezaa et al., 2009; Chakkaravarthi et al., 2007a; Hill et al., 2012). The bond lengths of C7—C8 and C6—C12 (1.4970 (2) and 1.5050 (2) Å), longer than that of C1—C7 (1.4580 (2) Å), may be a result of a resonant effect between C7—O9 (1.2485 (18) Å) carbonyl group and the aromatic ring. The bond length of C2—O10 (1.3466 (18) Å) is shorter than C4—O11 (1.3573 (19) Å). This may be a result of O10 being involved in an intramolecular hydrogen bond. The acetyl group is coplanar with the aromatic ring C2—C1—C7—O9 (dihedral angle of 7.2 (2) °). The torsion angles C7—C1—C6—C12 and C7—C1—C6—C5 [1.9 (2)° and -179.75 (13)°, respectively] indicate a planar conformation of the respective moieties. An intramolecular hydrogen bond was observed between the 2-phenolic hydrogen to the carbonyl group, O10—H10···O9 (D—H···A= 2.4983 (16) Å and O—H···O = 145°) to hold a carbonyl functionality in the coplanar plane of the aromatic ring. Intermolecular hydrogen bonds between the 4-hydroxyl group to the carbonyl oxygen O11—H11···O9 (D—H···A= 2.7862 (18) Å and O—H···O = 171°) link the molecules in to an extended polymeric structure (Fig. 1). The π···π stacking intermolecular interactions between two aromatic rings (centriod C1—C6) with a distance of (3.7478 (8) Å) (Fig. 2), further stabilize the three-dimensional network.
The culture media of the endophytic fungus Nodolisporium sp. (10 L) were extracted with EtOAc (6 x 500 mL). After removal of the solvent under reduced pressure, the EtOAc extract (2.25 g) was subjected to
over silica gel eluting with EtOAc:hexane (30-100%), followed by MeOH:EtOAc (0-100%) to yield fractions 1-19. After combination and removal of the solvents, fraction 4 (162.9 mg) was further purified by Sephadex LH-20 (20% H2O-MeOH) to yield 2,4-dihydroxy-6-methylacetophenone (133 mg). Single crystals were obtained by slow evaporation from EtOAc solution.For biological activities of acetophenone derivatives, see: Das & Khosla (2009); Suzuki et al. (2006); Tabuchi et al. (2014). For related structures, see: Azeezaa et al. (2009); Chakkaravarthi et al. (2007); Hill et al. (2012).
detailsThe methyl H atoms were constrained to an ideal geometry with C—H distances of 0.98 Å and each group was allowed to rotate freely about its C—C bond. All other hydrogen atoms were placed in idealized locations (C—H = 0.96–0.98 Å, O—H = 0.82 Å) and refined as riding with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(O, methyl C).
Data collection: COLLECT (Nonius, 2000); cell
SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015); molecular graphics: OLEX2 (Dolomanov et al., 2009) and Mercury (Macrae et al., 2008); software used to prepare material for publication: publCIF (Westrip, 2010).C9H10O3 | F(000) = 352 |
Mr = 166.17 | Dx = 1.367 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 7.3570 (3) Å | Cell parameters from 1754 reflections |
b = 15.001 (1) Å | θ = 1.0–27.5° |
c = 7.3180 (5) Å | µ = 0.10 mm−1 |
β = 91.017 (4)° | T = 298 K |
V = 807.50 (8) Å3 | Block, yellow |
Z = 4 | 0.25 × 0.25 × 0.25 mm |
Nonius KappaCCD diffractometer | 1319 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.028 |
Detector resolution: 9 pixels mm-1 | θmax = 27.5°, θmin = 3.1° |
CCD scans | h = −9→9 |
3260 measured reflections | k = −17→19 |
1828 independent reflections | l = −9→9 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.053 | H-atom parameters constrained |
wR(F2) = 0.150 | w = 1/[σ2(Fo2) + (0.0739P)2 + 0.1187P] where P = (Fo2 + 2Fc2)/3 |
S = 1.03 | (Δ/σ)max < 0.001 |
1828 reflections | Δρmax = 0.22 e Å−3 |
114 parameters | Δρmin = −0.17 e Å−3 |
0 restraints | Extinction correction: SHELXL2013 (Sheldrick, 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.06 (2) |
C9H10O3 | V = 807.50 (8) Å3 |
Mr = 166.17 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 7.3570 (3) Å | µ = 0.10 mm−1 |
b = 15.001 (1) Å | T = 298 K |
c = 7.3180 (5) Å | 0.25 × 0.25 × 0.25 mm |
β = 91.017 (4)° |
Nonius KappaCCD diffractometer | 1319 reflections with I > 2σ(I) |
3260 measured reflections | Rint = 0.028 |
1828 independent reflections |
R[F2 > 2σ(F2)] = 0.053 | 0 restraints |
wR(F2) = 0.150 | H-atom parameters constrained |
S = 1.03 | Δρmax = 0.22 e Å−3 |
1828 reflections | Δρmin = −0.17 e Å−3 |
114 parameters |
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 | ||
C1 | 0.70787 (19) | 0.22482 (9) | 0.77437 (17) | 0.0385 (4) | |
C2 | 0.70538 (18) | 0.32006 (10) | 0.77086 (18) | 0.0407 (4) | |
C3 | 0.8510 (2) | 0.37042 (10) | 0.83381 (19) | 0.0436 (4) | |
H3 | 0.8441 | 0.4381 | 0.8326 | 0.052* | |
C4 | 1.00510 (19) | 0.32826 (10) | 0.89794 (19) | 0.0447 (4) | |
C5 | 1.0142 (2) | 0.23520 (10) | 0.9001 (2) | 0.0446 (4) | |
H5 | 1.1320 | 0.2021 | 0.9410 | 0.053* | |
C6 | 0.87053 (19) | 0.18331 (10) | 0.84171 (17) | 0.0416 (4) | |
C7 | 0.5457 (2) | 0.17763 (10) | 0.70990 (19) | 0.0456 (4) | |
C8 | 0.5184 (3) | 0.07921 (13) | 0.7285 (3) | 0.0776 (6) | |
H8A | 0.6044 | 0.0483 | 0.6544 | 0.116* | |
H8B | 0.3972 | 0.0640 | 0.6891 | 0.116* | |
H8C | 0.5360 | 0.0622 | 0.8541 | 0.116* | |
O9 | 0.41657 (15) | 0.21912 (7) | 0.63688 (18) | 0.0588 (4) | |
O10 | 0.55972 (15) | 0.36627 (7) | 0.70969 (17) | 0.0552 (4) | |
H10 | 0.4830 | 0.3316 | 0.6688 | 0.083* | |
O11 | 1.14661 (16) | 0.37918 (8) | 0.95736 (18) | 0.0631 (4) | |
H11 | 1.2256 | 0.3471 | 1.0026 | 0.095* | |
C12 | 0.9014 (3) | 0.08414 (11) | 0.8510 (2) | 0.0607 (5) | |
H12A | 0.8165 | 0.0580 | 0.9335 | 0.073* | |
H12B | 1.0231 | 0.0725 | 0.8940 | 0.073* | |
H12C | 0.8842 | 0.0588 | 0.7315 | 0.073* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0408 (8) | 0.0373 (8) | 0.0373 (7) | 0.0021 (6) | −0.0033 (6) | 0.0009 (5) |
C2 | 0.0384 (7) | 0.0409 (8) | 0.0426 (7) | 0.0061 (6) | −0.0036 (5) | 0.0034 (6) |
C3 | 0.0438 (8) | 0.0373 (8) | 0.0496 (8) | 0.0011 (6) | −0.0048 (6) | 0.0029 (6) |
C4 | 0.0404 (8) | 0.0485 (9) | 0.0449 (8) | −0.0015 (6) | −0.0053 (6) | 0.0013 (6) |
C5 | 0.0402 (8) | 0.0481 (9) | 0.0452 (8) | 0.0092 (6) | −0.0059 (6) | 0.0017 (6) |
C6 | 0.0464 (8) | 0.0393 (8) | 0.0390 (7) | 0.0068 (6) | −0.0027 (6) | 0.0024 (5) |
C7 | 0.0462 (8) | 0.0469 (9) | 0.0436 (8) | −0.0020 (7) | −0.0047 (6) | 0.0001 (6) |
C8 | 0.0771 (13) | 0.0495 (11) | 0.1050 (15) | −0.0156 (9) | −0.0344 (11) | 0.0089 (10) |
O9 | 0.0443 (7) | 0.0558 (7) | 0.0756 (8) | −0.0015 (5) | −0.0172 (5) | 0.0004 (5) |
O10 | 0.0447 (7) | 0.0420 (6) | 0.0782 (8) | 0.0077 (5) | −0.0177 (5) | 0.0043 (5) |
O11 | 0.0475 (7) | 0.0556 (7) | 0.0853 (9) | −0.0071 (5) | −0.0213 (6) | 0.0027 (6) |
C12 | 0.0671 (11) | 0.0429 (9) | 0.0717 (11) | 0.0126 (8) | −0.0123 (8) | 0.0029 (8) |
C1—C6 | 1.4288 (18) | C6—C12 | 1.506 (2) |
C1—C2 | 1.429 (2) | C7—O9 | 1.2481 (18) |
C1—C7 | 1.4585 (19) | C7—C8 | 1.497 (2) |
C2—O10 | 1.3462 (16) | C8—H8A | 0.9600 |
C2—C3 | 1.3831 (19) | C8—H8B | 0.9600 |
C3—C4 | 1.374 (2) | C8—H8C | 0.9600 |
C3—H3 | 1.0170 | O10—H10 | 0.8200 |
C4—O11 | 1.3566 (18) | O11—H11 | 0.8200 |
C4—C5 | 1.398 (2) | C12—H12A | 0.9600 |
C5—C6 | 1.375 (2) | C12—H12B | 0.9600 |
C5—H5 | 1.0380 | C12—H12C | 0.9600 |
C6—C1—C2 | 116.89 (13) | O9—C7—C1 | 120.57 (14) |
C6—C1—C7 | 125.12 (13) | O9—C7—C8 | 115.38 (14) |
C2—C1—C7 | 117.99 (12) | C1—C7—C8 | 124.04 (14) |
O10—C2—C3 | 115.89 (13) | C7—C8—H8A | 109.5 |
O10—C2—C1 | 122.05 (13) | C7—C8—H8B | 109.5 |
C3—C2—C1 | 122.04 (12) | H8A—C8—H8B | 109.5 |
C4—C3—C2 | 119.47 (14) | C7—C8—H8C | 109.5 |
C4—C3—H3 | 120.3 | H8A—C8—H8C | 109.5 |
C2—C3—H3 | 120.3 | H8B—C8—H8C | 109.5 |
O11—C4—C3 | 118.31 (14) | C2—O10—H10 | 109.5 |
O11—C4—C5 | 121.49 (13) | C4—O11—H11 | 109.5 |
C3—C4—C5 | 120.19 (13) | C6—C12—H12A | 109.5 |
C6—C5—C4 | 121.71 (13) | C6—C12—H12B | 109.5 |
C6—C5—H5 | 116.9 | H12A—C12—H12B | 109.5 |
C4—C5—H5 | 121.4 | C6—C12—H12C | 109.5 |
C5—C6—C1 | 119.68 (13) | H12A—C12—H12C | 109.5 |
C5—C6—C12 | 115.52 (13) | H12B—C12—H12C | 109.5 |
C1—C6—C12 | 124.79 (14) | ||
C6—C1—C2—O10 | 179.79 (12) | C4—C5—C6—C1 | 0.9 (2) |
C7—C1—C2—O10 | −0.3 (2) | C4—C5—C6—C12 | 179.57 (14) |
C6—C1—C2—C3 | −1.66 (19) | C2—C1—C6—C5 | 0.41 (19) |
C7—C1—C2—C3 | 178.24 (13) | C7—C1—C6—C5 | −179.48 (13) |
O10—C2—C3—C4 | −179.77 (13) | C2—C1—C6—C12 | −178.14 (14) |
C1—C2—C3—C4 | 1.6 (2) | C7—C1—C6—C12 | 2.0 (2) |
C2—C3—C4—O11 | 179.41 (13) | C6—C1—C7—O9 | −172.96 (13) |
C2—C3—C4—C5 | −0.2 (2) | C2—C1—C7—O9 | 7.2 (2) |
O11—C4—C5—C6 | 179.36 (14) | C6—C1—C7—C8 | 8.5 (2) |
C3—C4—C5—C6 | −1.0 (2) | C2—C1—C7—C8 | −171.41 (16) |
D—H···A | D—H | H···A | D···A | D—H···A |
O10—H10···O9 | 0.82 | 1.77 | 2.4991 (16) | 147 |
O11—H11···O9i | 0.82 | 1.97 | 2.7843 (16) | 173 |
Symmetry code: (i) x+1, −y+1/2, z+1/2. |
D—H···A | D—H | H···A | D···A | D—H···A |
O10—H10···O9 | 0.82 | 1.77 | 2.4991 (16) | 147.0 |
O11—H11···O9i | 0.82 | 1.97 | 2.7843 (16) | 172.8 |
Symmetry code: (i) x+1, −y+1/2, z+1/2. |
Acknowledgements
We acknowledge financial support from the Thailand Research Fund, the Office of the Higher Education Commission and Mahidol University under the National Research Universities Initiative. This study was conducted in a facility supported by the Center of Excellence for Innovation in Chemistry (PERCH–CIC).
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