organic compounds
2-(2-Hydroxypropan-2-yl)-6-(prop-2-ynyloxy)-1-benzofuran-3(2H)-one
aResearch Center for Synthesis and Catalysis, Department of Chemistry, University of Johannesburg (APK Campus), PO Box 524, Auckland Park, Johannesburg, 2006, South Africa
*Correspondence e-mail: zhphasha@uj.ac.za
In the title compound, C14H14O4, the prop-2-ynyloxy O—C—C≡C plane [maximum deviation = 0.0116 (12) Å] forms a dihedral angle of 78.44 (9)° with the benzofuran-3(2H)-one ring system. In the crystal, molecules are linked by O—H⋯O hydrogen bonds, forming a tape along the a-axis direction. C—H⋯O interactions are observed between the tapes.
Related literature
For background to the development of hybrid drug candidates against tuberculosis, malaria and cancer, see: Morphy et al. (2004). For details of the synthesis of the title compound, see: Hoogendoorn et al. (2011).
Experimental
Crystal data
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Refinement
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Data collection: APEX2 (Bruker, 2011); cell SAINT (Bruker, 2008); 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
10.1107/S1600536812045606/is5212sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536812045606/is5212Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536812045606/is5212Isup3.cml
A solution of 6-hydroxy-benzofuran-3-one (1 g, 6.66 mmol) in dry acetone was treated with potassium carbonate (1.3 g, 9.32 mmol). The reaction mixture was heated at a temperature of 70–80 °C for about 30 minutes and then propargyl bromide (1.6 ml, 14.65 mmol) was added to it. The combined solution was stirred for about 2.5 h and concentrated under vacuum. The residue was diluted with water and extracted three times with ethyl acetate. The combined organic layer was washed with brine and water and dried over anhydrous magnesium sulfate. After that filtered and the filtrate solid product was recrystalized from ethyl acetate and hexane to afford 70% of the target compound as yellow crystal (m.p. 118–120 °C).
All hydrogen atoms were positioned in geometrically idealized positions with C—H = 1.00 Å (methine), 0.99 Å (methylene), 0.98 Å (methyl), 0.95 Å (aromatic), and 0.84 Å (hydroxyl). All hydrogen atoms were allowed to ride on their parent atoms with Uiso(H) = 1.2Ueq, except for the methyl and hydroxyl hydrogen atoms where Uiso(H) = 1.5Ueq was utilized. The initial positions of methyl hydrogen atoms were located in a difference Fourier map and refined as a fixed rotor.
In our research in the development of hybrid drug candidates against tuberculosis, malaria and cancer (Morphy et al., 2004), the title compound was synthesized as a building starting material. The title compound was synthesized by the reaction of 6-hydroxy-benzofuran-3-one with propargyl bromide in the presence of potassium carbonate at relatively high temperature (Hoogendoorn et al., 2011). Herein we report the
of the title compound.In the
of the title compound, the propyn-1-yloxy group (C1–C3/O3) forms a dihedral angle of 78.44 (9)° with the fused benzofuran-3-one ring system (Fig. 1). The crystal packing is stabilized by O—H···O interactions (Table 1 and Fig. 2). The C—H···O interactions are also observed (Table 1).For background to the development of hybrid drug candidates against tuberculosis, malaria and cancer, see: Morphy et al. (2004). For details of the synthesis of the title compound, see: Hoogendoorn et al. (2011).
Data collection: APEX2 (Bruker, 2011); cell
SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); 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).C14H14O4 | Z = 2 |
Mr = 246.25 | F(000) = 260 |
Triclinic, P1 | Dx = 1.38 Mg m−3 |
Hall symbol: -P 1 | Cu Kα radiation, λ = 1.54178 Å |
a = 5.4199 (2) Å | Cell parameters from 4605 reflections |
b = 9.0785 (3) Å | θ = 4.9–66.1° |
c = 12.3555 (4) Å | µ = 0.84 mm−1 |
α = 85.758 (2)° | T = 100 K |
β = 80.455 (2)° | Needle, colourless |
γ = 81.829 (2)° | 0.39 × 0.11 × 0.11 mm |
V = 592.65 (4) Å3 |
Bruker APEX DUO 4K CCD diffractometer | 1983 independent reflections |
Incoatec Quazar Multilayer Mirror monochromator | 1888 reflections with I > 2σ(I) |
Detector resolution: 8.4 pixels mm-1 | Rint = 0.025 |
φ and ω scans | θmax = 66.3°, θmin = 4.9° |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −4→6 |
Tmin = 0.736, Tmax = 0.913 | k = −10→10 |
10266 measured reflections | l = −14→14 |
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)] = 0.032 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.082 | H-atom parameters constrained |
S = 1.03 | w = 1/[σ2(Fo2) + (0.0364P)2 + 0.2704P] where P = (Fo2 + 2Fc2)/3 |
1983 reflections | (Δ/σ)max < 0.001 |
166 parameters | Δρmax = 0.21 e Å−3 |
0 restraints | Δρmin = −0.17 e Å−3 |
C14H14O4 | γ = 81.829 (2)° |
Mr = 246.25 | V = 592.65 (4) Å3 |
Triclinic, P1 | Z = 2 |
a = 5.4199 (2) Å | Cu Kα radiation |
b = 9.0785 (3) Å | µ = 0.84 mm−1 |
c = 12.3555 (4) Å | T = 100 K |
α = 85.758 (2)° | 0.39 × 0.11 × 0.11 mm |
β = 80.455 (2)° |
Bruker APEX DUO 4K CCD diffractometer | 1983 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | 1888 reflections with I > 2σ(I) |
Tmin = 0.736, Tmax = 0.913 | Rint = 0.025 |
10266 measured reflections |
R[F2 > 2σ(F2)] = 0.032 | 0 restraints |
wR(F2) = 0.082 | H-atom parameters constrained |
S = 1.03 | Δρmax = 0.21 e Å−3 |
1983 reflections | Δρmin = −0.17 e Å−3 |
166 parameters |
Experimental. Analytical data: 1H NMR (CDCl3, 400 MHZ): δ 7.55 (d, 1H), 6.69 (s, 1H), 6.66 (s, 1H), 4.74 (s, 2H), 4.36 (s, 1H), 3.26 (s, 1H), 2.58 (s, 1H), 1.33 (s, 3H), 1.18 (s, 3H); 13C NMR (CDCl3, 400 MHZ): δ 199.0, 175.0, 166.2, 125.4, 115.5, 112.1, 97.4, 89.8, 72.3, 56.3, 25.9, 23.9. The intensity data was collected on a Bruker Apex DUO 4 K CCD diffractometer using an exposure time of 5 s/frame. A total of 4558 frames were collected with a frame width of 1° covering up to θ = 66.28° with 95.2% completeness accomplished. |
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. |
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 > 2σ(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 | 0.2006 (3) | 0.84616 (15) | 0.02726 (11) | 0.0261 (3) | |
H1 | 0.1077 | 0.8209 | −0.0259 | 0.031* | |
C2 | 0.3167 (2) | 0.87773 (14) | 0.09371 (10) | 0.0223 (3) | |
C3 | 0.4670 (2) | 0.91785 (15) | 0.17253 (10) | 0.0223 (3) | |
H3A | 0.6387 | 0.9299 | 0.1339 | 0.027* | |
H3B | 0.3894 | 1.0148 | 0.2026 | 0.027* | |
C4 | 0.2852 (2) | 0.80294 (13) | 0.34321 (10) | 0.0172 (3) | |
C5 | 0.0548 (2) | 0.89754 (13) | 0.34541 (10) | 0.0189 (3) | |
H5 | 0.0309 | 0.9688 | 0.2866 | 0.023* | |
C6 | −0.1355 (2) | 0.88612 (13) | 0.43326 (10) | 0.0180 (3) | |
H6 | −0.2907 | 0.9504 | 0.4362 | 0.022* | |
C7 | −0.0975 (2) | 0.77883 (13) | 0.51799 (10) | 0.0167 (3) | |
C8 | 0.1301 (2) | 0.68501 (13) | 0.51207 (10) | 0.0164 (3) | |
C9 | 0.3268 (2) | 0.69443 (13) | 0.42660 (10) | 0.0177 (3) | |
H9 | 0.4822 | 0.6306 | 0.4246 | 0.021* | |
C10 | −0.2529 (2) | 0.73992 (13) | 0.61999 (10) | 0.0173 (3) | |
C11 | −0.0979 (2) | 0.60810 (13) | 0.67327 (10) | 0.0177 (3) | |
H11 | −0.1864 | 0.5181 | 0.6763 | 0.021* | |
C12 | −0.0406 (2) | 0.62882 (13) | 0.78842 (10) | 0.0183 (3) | |
C13 | 0.1469 (2) | 0.49897 (14) | 0.82127 (11) | 0.0237 (3) | |
H13A | 0.3049 | 0.4962 | 0.7693 | 0.036* | |
H13B | 0.0765 | 0.4055 | 0.8203 | 0.036* | |
H13C | 0.1802 | 0.5115 | 0.8954 | 0.036* | |
C14 | −0.2814 (2) | 0.64049 (15) | 0.87195 (10) | 0.0233 (3) | |
H14A | −0.2438 | 0.6637 | 0.9432 | 0.035* | |
H14B | −0.3504 | 0.5455 | 0.8793 | 0.035* | |
H14C | −0.4052 | 0.7198 | 0.8472 | 0.035* | |
O1 | 0.05931 (15) | 0.76695 (9) | 0.78783 (7) | 0.0193 (2) | |
H | 0.2022 | 0.7612 | 0.7486 | 0.029* | |
O2 | 0.14038 (15) | 0.58334 (9) | 0.59873 (7) | 0.0187 (2) | |
O3 | 0.48574 (16) | 0.80822 (10) | 0.26152 (7) | 0.0215 (2) | |
O4 | −0.46595 (15) | 0.79629 (10) | 0.65811 (7) | 0.0215 (2) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0272 (7) | 0.0300 (7) | 0.0206 (7) | −0.0034 (6) | −0.0019 (5) | −0.0033 (5) |
C2 | 0.0241 (7) | 0.0221 (6) | 0.0176 (6) | −0.0009 (5) | 0.0036 (5) | 0.0003 (5) |
C3 | 0.0251 (7) | 0.0247 (7) | 0.0167 (6) | −0.0065 (5) | −0.0002 (5) | 0.0016 (5) |
C4 | 0.0184 (6) | 0.0194 (6) | 0.0144 (6) | −0.0047 (5) | −0.0010 (5) | −0.0043 (5) |
C5 | 0.0222 (6) | 0.0188 (6) | 0.0161 (6) | −0.0023 (5) | −0.0050 (5) | −0.0006 (5) |
C6 | 0.0173 (6) | 0.0185 (6) | 0.0187 (6) | −0.0003 (5) | −0.0047 (5) | −0.0033 (5) |
C7 | 0.0163 (6) | 0.0180 (6) | 0.0166 (6) | −0.0030 (4) | −0.0035 (5) | −0.0038 (5) |
C8 | 0.0204 (6) | 0.0151 (6) | 0.0150 (6) | −0.0034 (5) | −0.0049 (5) | −0.0024 (4) |
C9 | 0.0171 (6) | 0.0186 (6) | 0.0175 (6) | −0.0002 (5) | −0.0034 (5) | −0.0038 (5) |
C10 | 0.0166 (6) | 0.0197 (6) | 0.0174 (6) | −0.0050 (5) | −0.0041 (5) | −0.0041 (5) |
C11 | 0.0161 (6) | 0.0187 (6) | 0.0176 (6) | −0.0037 (5) | 0.0003 (5) | −0.0010 (5) |
C12 | 0.0184 (6) | 0.0195 (6) | 0.0171 (6) | −0.0046 (5) | −0.0021 (5) | 0.0010 (5) |
C13 | 0.0242 (7) | 0.0239 (7) | 0.0220 (7) | −0.0013 (5) | −0.0043 (5) | 0.0033 (5) |
C14 | 0.0214 (7) | 0.0302 (7) | 0.0175 (6) | −0.0045 (5) | −0.0013 (5) | 0.0024 (5) |
O1 | 0.0183 (5) | 0.0207 (5) | 0.0188 (4) | −0.0044 (3) | −0.0002 (3) | −0.0024 (3) |
O2 | 0.0204 (5) | 0.0182 (4) | 0.0156 (4) | 0.0009 (3) | −0.0002 (3) | 0.0006 (3) |
O3 | 0.0197 (5) | 0.0272 (5) | 0.0155 (4) | −0.0010 (3) | 0.0005 (3) | 0.0015 (3) |
O4 | 0.0154 (5) | 0.0279 (5) | 0.0203 (5) | −0.0017 (3) | −0.0014 (3) | −0.0012 (4) |
C1—C2 | 1.187 (2) | C9—H9 | 0.95 |
C1—H1 | 0.95 | C10—O4 | 1.2264 (15) |
C2—C3 | 1.4647 (18) | C10—C11 | 1.5338 (17) |
C3—O3 | 1.4339 (15) | C11—O2 | 1.4561 (14) |
C3—H3A | 0.99 | C11—C12 | 1.5359 (17) |
C3—H3B | 0.99 | C11—H11 | 1 |
C4—O3 | 1.3586 (14) | C12—O1 | 1.4339 (14) |
C4—C9 | 1.3952 (17) | C12—C14 | 1.5198 (17) |
C4—C5 | 1.4092 (18) | C12—C13 | 1.5206 (17) |
C5—C6 | 1.3767 (17) | C13—H13A | 0.98 |
C5—H5 | 0.95 | C13—H13B | 0.98 |
C6—C7 | 1.3968 (17) | C13—H13C | 0.98 |
C6—H6 | 0.95 | C14—H14A | 0.98 |
C7—C8 | 1.3906 (17) | C14—H14B | 0.98 |
C7—C10 | 1.4454 (17) | C14—H14C | 0.98 |
C8—O2 | 1.3640 (15) | O1—H | 0.84 |
C8—C9 | 1.3777 (17) | ||
C2—C1—H1 | 180 | C7—C10—C11 | 105.72 (10) |
C1—C2—C3 | 177.97 (13) | O2—C11—C10 | 105.17 (9) |
O3—C3—C2 | 112.50 (10) | O2—C11—C12 | 108.40 (9) |
O3—C3—H3A | 109.1 | C10—C11—C12 | 116.67 (10) |
C2—C3—H3A | 109.1 | O2—C11—H11 | 108.8 |
O3—C3—H3B | 109.1 | C10—C11—H11 | 108.8 |
C2—C3—H3B | 109.1 | C12—C11—H11 | 108.8 |
H3A—C3—H3B | 107.8 | O1—C12—C14 | 106.41 (10) |
O3—C4—C9 | 113.90 (10) | O1—C12—C13 | 110.61 (10) |
O3—C4—C5 | 123.96 (11) | C14—C12—C13 | 110.22 (10) |
C9—C4—C5 | 122.14 (11) | O1—C12—C11 | 109.16 (9) |
C6—C5—C4 | 119.68 (11) | C14—C12—C11 | 110.66 (10) |
C6—C5—H5 | 120.2 | C13—C12—C11 | 109.74 (10) |
C4—C5—H5 | 120.2 | C12—C13—H13A | 109.5 |
C5—C6—C7 | 119.14 (11) | C12—C13—H13B | 109.5 |
C5—C6—H6 | 120.4 | H13A—C13—H13B | 109.5 |
C7—C6—H6 | 120.4 | C12—C13—H13C | 109.5 |
C8—C7—C6 | 119.71 (11) | H13A—C13—H13C | 109.5 |
C8—C7—C10 | 107.37 (10) | H13B—C13—H13C | 109.5 |
C6—C7—C10 | 132.92 (11) | C12—C14—H14A | 109.5 |
O2—C8—C9 | 123.28 (11) | C12—C14—H14B | 109.5 |
O2—C8—C7 | 113.74 (10) | H14A—C14—H14B | 109.5 |
C9—C8—C7 | 122.98 (11) | C12—C14—H14C | 109.5 |
C8—C9—C4 | 116.33 (11) | H14A—C14—H14C | 109.5 |
C8—C9—H9 | 121.8 | H14B—C14—H14C | 109.5 |
C4—C9—H9 | 121.8 | C12—O1—H | 109.5 |
O4—C10—C7 | 128.78 (11) | C8—O2—C11 | 107.95 (9) |
O4—C10—C11 | 125.50 (11) | C4—O3—C3 | 118.88 (9) |
O3—C4—C5—C6 | −178.39 (10) | O4—C10—C11—O2 | −179.31 (10) |
C9—C4—C5—C6 | 1.43 (18) | C7—C10—C11—O2 | 1.55 (12) |
C4—C5—C6—C7 | −1.02 (17) | O4—C10—C11—C12 | −59.16 (16) |
C5—C6—C7—C8 | −0.40 (17) | C7—C10—C11—C12 | 121.70 (11) |
C5—C6—C7—C10 | 178.94 (12) | O2—C11—C12—O1 | 68.57 (11) |
C6—C7—C8—O2 | −178.57 (10) | C10—C11—C12—O1 | −49.84 (13) |
C10—C7—C8—O2 | 1.93 (14) | O2—C11—C12—C14 | −174.64 (9) |
C6—C7—C8—C9 | 1.55 (18) | C10—C11—C12—C14 | 66.94 (13) |
C10—C7—C8—C9 | −177.94 (11) | O2—C11—C12—C13 | −52.79 (12) |
O2—C8—C9—C4 | 178.99 (10) | C10—C11—C12—C13 | −171.21 (10) |
C7—C8—C9—C4 | −1.15 (18) | C9—C8—O2—C11 | 178.98 (10) |
O3—C4—C9—C8 | 179.49 (10) | C7—C8—O2—C11 | −0.89 (13) |
C5—C4—C9—C8 | −0.34 (17) | C10—C11—O2—C8 | −0.46 (12) |
C8—C7—C10—O4 | 178.84 (12) | C12—C11—O2—C8 | −125.94 (10) |
C6—C7—C10—O4 | −0.6 (2) | C9—C4—O3—C3 | −178.56 (10) |
C8—C7—C10—C11 | −2.06 (12) | C5—C4—O3—C3 | 1.28 (17) |
C6—C7—C10—C11 | 178.53 (12) | C2—C3—O3—C4 | −76.90 (13) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H···O4i | 0.84 | 2.01 | 2.8328 (12) | 167 |
C1—H1···O1ii | 0.95 | 2.45 | 3.3283 (16) | 154 |
C5—H5···O1iii | 0.95 | 2.52 | 3.3809 (15) | 152 |
Symmetry codes: (i) x+1, y, z; (ii) x, y, z−1; (iii) −x, −y+2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C14H14O4 |
Mr | 246.25 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 100 |
a, b, c (Å) | 5.4199 (2), 9.0785 (3), 12.3555 (4) |
α, β, γ (°) | 85.758 (2), 80.455 (2), 81.829 (2) |
V (Å3) | 592.65 (4) |
Z | 2 |
Radiation type | Cu Kα |
µ (mm−1) | 0.84 |
Crystal size (mm) | 0.39 × 0.11 × 0.11 |
Data collection | |
Diffractometer | Bruker APEX DUO 4K CCD |
Absorption correction | Multi-scan (SADABS; Bruker, 2008) |
Tmin, Tmax | 0.736, 0.913 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 10266, 1983, 1888 |
Rint | 0.025 |
(sin θ/λ)max (Å−1) | 0.594 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.032, 0.082, 1.03 |
No. of reflections | 1983 |
No. of parameters | 166 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.21, −0.17 |
Computer programs: APEX2 (Bruker, 2011), SAINT (Bruker, 2008), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H···O4i | 0.84 | 2.01 | 2.8328 (12) | 167.3 |
C1—H1···O1ii | 0.95 | 2.45 | 3.3283 (16) | 153.5 |
C5—H5···O1iii | 0.95 | 2.52 | 3.3809 (15) | 151.6 |
Symmetry codes: (i) x+1, y, z; (ii) x, y, z−1; (iii) −x, −y+2, −z+1. |
Acknowledgements
Research funds of the University of Johannesburg is gratefully acknowledged.
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.
In our research in the development of hybrid drug candidates against tuberculosis, malaria and cancer (Morphy et al., 2004), the title compound was synthesized as a building starting material. The title compound was synthesized by the reaction of 6-hydroxy-benzofuran-3-one with propargyl bromide in the presence of potassium carbonate at relatively high temperature (Hoogendoorn et al., 2011). Herein we report the crystal structure of the title compound.
In the crystal structure of the title compound, the propyn-1-yloxy group (C1–C3/O3) forms a dihedral angle of 78.44 (9)° with the fused benzofuran-3-one ring system (Fig. 1). The crystal packing is stabilized by O—H···O interactions (Table 1 and Fig. 2). The C—H···O interactions are also observed (Table 1).