Acta Cryst. (2012). E68, o3072 [ doi:10.1107/S1600536812041207 ]
The title compound, C11H11NO2, was synthesized by chemoselective N-acetylation of 4-aminophenol followed by reaction with propargyl bromide in the presence of K2CO3. the acetamide and propyn-1-yloxy substituents form dihedral angles of 18.31 (6) and 7.01 (10)°, respectively, with the benzene ring. In the crystal, molecules are linked by N-H
O hydrogen bonds into chains along [010]. C-HO and C-H![[pi]](/logos/entities/pi_rmgif.gif)
interactions also occur.
A solution of N-(hydoxy-phenyl)acetamide (450 mg, 2.980 mmol), synthesized by chemoselective acetylation of 4-aminophenol using 1 equivalence of acetic anhydride, in dry acetone was treated with potassium carbonate (576 mg, 4.17 mmol). The reaction mixture was stirred under reflux for about 30 minutes followed by addition of propargyl bromide (0.8 ml, 6.56 mmol). The combined solution was stirred for additional 3 h and concentrated under vacuo. 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 sodium sulfate, filtered and solvent evaporated. The solid crude product was recrystallized from dichloromethane and hexane to afford 71% of the target compound as pale yellow crystals. The melting point of the crystalline material was found to similar as reported in literature (Reppe, 1955).
All hydrogen atoms were positioned in geometrically idealized positions with C—H = 0.99 Å (methylene), 0.98 Å (methyl) and 0.95 Å (aromatic and acetylenic). The amide hydrogen atom were obtained from a Fourier difference map and refined with varying coordinates. All these hydrogen atoms were allowed to ride on their parent atoms with Uiso(H) = 1.2Ueq, except for methyl and amide hydrogen atoms where Uiso(H) = 1.5Ueq was utilized. The initial positions of methyl hydrogen atoms were located from a Fourier difference map and refined as a fixed rotor.
Data collection: APEX2 (Bruker, 2011); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT and XPREP (Bruker, 2008); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg & Putz, 2005); software used to prepare material for publication: WinGX (Farrugia, 1999).
![[Figure 1]](./nc2291fig1thm.gif)
| Fig. 1. Crystal structure of the title compound with labeling and displacement ellipsoids drawn at the 50% probability level.. |
![[Figure 2]](./nc2291fig2thm.gif)
| Fig. 2. Packing diagram showing the molecules linked by infinite one-dimensional N—H···O chains in the [010] direction. Hydrogen bonds and C—H···O/π interactions are shown as red and black dashed lines respectively. |
| C11H11NO2 | F(000) = 400 |
| Mr = 189.21 | Dx = 1.323 Mg m−3 |
| Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
| Hall symbol: -P 2ybc | Cell parameters from 3099 reflections |
| a = 13.973 (2) Å | θ = 2.7–28.4° |
| b = 9.1794 (13) Å | µ = 0.09 mm−1 |
| c = 7.5105 (11) Å | T = 100 K |
| β = 99.441 (4)° | Block, pale yellow |
| V = 950.3 (2) Å3 | 0.3 × 0.26 × 0.23 mm |
| Z = 4 |
| Bruker APEX DUO 4K CCD diffractometer | 2388 independent reflections |
| Graphite monochromator | 2103 reflections with I > 2σ(I) |
| Detector resolution: 8.4 pixels mm-1 | Rint = 0.018 |
| φ and ω scans | θmax = 28.5°, θmin = 2.7° |
| Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −18→18 |
| Tmin = 0.969, Tmax = 0.981 | k = −12→11 |
| 6753 measured reflections | l = −10→10 |
| 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)] = 0.037 | Hydrogen site location: inferred from neighbouring sites |
| wR(F2) = 0.100 | H atoms treated by a mixture of independent and constrained refinement |
| S = 1.04 | w = 1/[σ2(Fo2) + (0.0509P)2 + 0.3049P] where P = (Fo2 + 2Fc2)/3 |
| 2388 reflections | (Δ/σ)max < 0.001 |
| 131 parameters | Δρmax = 0.28 e Å−3 |
| 0 restraints | Δρmin = −0.24 e Å−3 |
| C11H11NO2 | V = 950.3 (2) Å3 |
| Mr = 189.21 | Z = 4 |
| Monoclinic, P21/c | Mo Kα radiation |
| a = 13.973 (2) Å | µ = 0.09 mm−1 |
| b = 9.1794 (13) Å | T = 100 K |
| c = 7.5105 (11) Å | 0.3 × 0.26 × 0.23 mm |
| β = 99.441 (4)° |
| Bruker APEX DUO 4K CCD diffractometer | 2388 independent reflections |
| Absorption correction: multi-scan (SADABS; Bruker, 2008) | 2103 reflections with I > 2σ(I) |
| Tmin = 0.969, Tmax = 0.981 | Rint = 0.018 |
| 6753 measured reflections | θmax = 28.5° |
| R[F2 > 2σ(F2)] = 0.037 | H atoms treated by a mixture of independent and constrained refinement |
| wR(F2) = 0.100 | Δρmax = 0.28 e Å−3 |
| S = 1.04 | Δρmin = −0.24 e Å−3 |
| 2388 reflections | Absolute structure: ? |
| 131 parameters | Flack parameter: ? |
| 0 restraints | Rogers parameter: ? |
Experimental. The intensity data was collected on a Bruker Apex DUO 4 K CCD diffractometer using an exposure time of 20 s/frame. A total of 735 frames were collected with a frame width of 0.5° covering up to θ = 28.47° with 99.3% completeness accomplished. Analytical data: mp: 110 - 111 °C (Lit. 109 - 111 °C; Reppe, 1955); 1H NMR (CDCl3, 400 MHz): d 7.57 (s, 1H), 7.38 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 4.63 (s, 2H), 2.49 (s, 1H), 2.12 (s, 3H); 13C NMR (CDCl3,400 MHz): d 168.4, 154.3, 131.9, 121.8, 115.3, 78.5, 75.5, 56.1, 24.4. |
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 | ||
| O1 | 0.44065 (5) | 0.09706 (8) | 0.16260 (10) | 0.01982 (18) | |
| O2 | −0.00853 (5) | 0.27539 (8) | −0.14889 (10) | 0.02019 (18) | |
| N1 | 0.05791 (6) | 0.05346 (9) | −0.18684 (12) | 0.01555 (19) | |
| C1 | 0.63468 (9) | 0.09825 (14) | 0.49415 (17) | 0.0288 (3) | |
| H1A | 0.6943 | 0.0641 | 0.5601 | 0.035* | |
| C2 | 0.56036 (8) | 0.14084 (12) | 0.41199 (15) | 0.0215 (2) | |
| C3 | 0.46720 (8) | 0.19131 (12) | 0.31532 (14) | 0.0202 (2) | |
| H3A | 0.4174 | 0.1874 | 0.395 | 0.024* | |
| H3B | 0.4726 | 0.2931 | 0.2748 | 0.024* | |
| C4 | 0.34482 (7) | 0.09626 (11) | 0.08432 (13) | 0.0160 (2) | |
| C5 | 0.27561 (7) | 0.19574 (11) | 0.12113 (13) | 0.0165 (2) | |
| H5 | 0.2934 | 0.2712 | 0.2068 | 0.02* | |
| C6 | 0.17996 (7) | 0.18471 (11) | 0.03218 (13) | 0.0160 (2) | |
| H6 | 0.1327 | 0.2524 | 0.0582 | 0.019* | |
| C7 | 0.15352 (7) | 0.07514 (10) | −0.09429 (13) | 0.0143 (2) | |
| C8 | −0.01572 (7) | 0.15035 (11) | −0.20997 (13) | 0.0156 (2) | |
| C9 | −0.10956 (7) | 0.09587 (11) | −0.31599 (14) | 0.0192 (2) | |
| H9A | −0.1605 | 0.1005 | −0.2407 | 0.029* | |
| H9B | −0.1014 | −0.0051 | −0.353 | 0.029* | |
| H9C | −0.1279 | 0.1568 | −0.4233 | 0.029* | |
| C10 | 0.22426 (7) | −0.02335 (11) | −0.13094 (14) | 0.0169 (2) | |
| H10 | 0.207 | −0.0982 | −0.2177 | 0.02* | |
| C11 | 0.31883 (7) | −0.01321 (11) | −0.04271 (14) | 0.0175 (2) | |
| H11 | 0.3661 | −0.0809 | −0.0687 | 0.021* | |
| H1 | 0.0464 (10) | −0.0325 (16) | −0.2373 (18) | 0.021* |
| U11 | U22 | U33 | U12 | U13 | U23 | |
| O1 | 0.0138 (4) | 0.0255 (4) | 0.0184 (4) | 0.0032 (3) | −0.0024 (3) | −0.0051 (3) |
| O2 | 0.0192 (4) | 0.0149 (3) | 0.0248 (4) | 0.0026 (3) | −0.0015 (3) | −0.0008 (3) |
| N1 | 0.0139 (4) | 0.0124 (4) | 0.0192 (4) | −0.0008 (3) | −0.0006 (3) | −0.0010 (3) |
| C1 | 0.0196 (6) | 0.0338 (6) | 0.0302 (6) | −0.0025 (5) | −0.0039 (5) | 0.0011 (5) |
| C2 | 0.0192 (5) | 0.0236 (5) | 0.0211 (5) | −0.0036 (4) | 0.0014 (4) | −0.0027 (4) |
| C3 | 0.0190 (5) | 0.0213 (5) | 0.0189 (5) | 0.0002 (4) | −0.0010 (4) | −0.0032 (4) |
| C4 | 0.0136 (5) | 0.0190 (5) | 0.0148 (4) | 0.0012 (4) | 0.0000 (4) | 0.0021 (3) |
| C5 | 0.0168 (5) | 0.0165 (4) | 0.0154 (4) | 0.0005 (4) | 0.0003 (4) | −0.0022 (3) |
| C6 | 0.0162 (5) | 0.0150 (4) | 0.0168 (5) | 0.0020 (4) | 0.0022 (4) | 0.0000 (3) |
| C7 | 0.0140 (5) | 0.0138 (4) | 0.0146 (4) | −0.0001 (3) | 0.0007 (3) | 0.0027 (3) |
| C8 | 0.0146 (5) | 0.0156 (4) | 0.0162 (4) | −0.0001 (3) | 0.0014 (4) | 0.0032 (3) |
| C9 | 0.0147 (5) | 0.0184 (5) | 0.0234 (5) | −0.0007 (4) | −0.0006 (4) | 0.0018 (4) |
| C10 | 0.0181 (5) | 0.0139 (4) | 0.0179 (5) | 0.0004 (4) | 0.0006 (4) | −0.0017 (3) |
| C11 | 0.0171 (5) | 0.0159 (4) | 0.0191 (5) | 0.0040 (4) | 0.0016 (4) | −0.0002 (4) |
| O1—C4 | 1.3713 (12) | C5—C6 | 1.3965 (14) |
| O1—C3 | 1.4360 (12) | C5—H5 | 0.95 |
| O2—C8 | 1.2340 (12) | C6—C7 | 1.3911 (13) |
| N1—C8 | 1.3495 (13) | C6—H6 | 0.95 |
| N1—C7 | 1.4152 (13) | C7—C10 | 1.3999 (14) |
| N1—H1 | 0.879 (14) | C8—C9 | 1.5036 (14) |
| C1—C2 | 1.1840 (17) | C9—H9A | 0.98 |
| C1—H1A | 0.95 | C9—H9B | 0.98 |
| C2—C3 | 1.4582 (15) | C9—H9C | 0.98 |
| C3—H3A | 0.99 | C10—C11 | 1.3807 (14) |
| C3—H3B | 0.99 | C10—H10 | 0.95 |
| C4—C5 | 1.3903 (14) | C11—H11 | 0.95 |
| C4—C11 | 1.3922 (14) | ||
| C4—O1—C3 | 116.86 (8) | C5—C6—H6 | 119.8 |
| C8—N1—C7 | 127.50 (9) | C6—C7—C10 | 118.96 (9) |
| C8—N1—H1 | 117.0 (9) | C6—C7—N1 | 124.10 (9) |
| C7—N1—H1 | 115.5 (9) | C10—C7—N1 | 116.92 (9) |
| C2—C1—H1A | 180 | O2—C8—N1 | 123.46 (9) |
| C1—C2—C3 | 178.14 (12) | O2—C8—C9 | 121.13 (9) |
| O1—C3—C2 | 107.39 (8) | N1—C8—C9 | 115.41 (9) |
| O1—C3—H3A | 110.2 | C8—C9—H9A | 109.5 |
| C2—C3—H3A | 110.2 | C8—C9—H9B | 109.5 |
| O1—C3—H3B | 110.2 | H9A—C9—H9B | 109.5 |
| C2—C3—H3B | 110.2 | C8—C9—H9C | 109.5 |
| H3A—C3—H3B | 108.5 | H9A—C9—H9C | 109.5 |
| O1—C4—C5 | 124.98 (9) | H9B—C9—H9C | 109.5 |
| O1—C4—C11 | 115.11 (9) | C11—C10—C7 | 120.87 (9) |
| C5—C4—C11 | 119.90 (9) | C11—C10—H10 | 119.6 |
| C4—C5—C6 | 119.98 (9) | C7—C10—H10 | 119.6 |
| C4—C5—H5 | 120 | C10—C11—C4 | 119.94 (9) |
| C6—C5—H5 | 120 | C10—C11—H11 | 120 |
| C7—C6—C5 | 120.34 (9) | C4—C11—H11 | 120 |
| C7—C6—H6 | 119.8 | ||
| C4—O1—C3—C2 | 161.20 (9) | C8—N1—C7—C10 | −162.01 (10) |
| C3—O1—C4—C5 | 11.37 (14) | C7—N1—C8—O2 | −0.68 (16) |
| C3—O1—C4—C11 | −169.65 (9) | C7—N1—C8—C9 | 179.68 (9) |
| O1—C4—C5—C6 | 179.65 (9) | C6—C7—C10—C11 | 0.40 (15) |
| C11—C4—C5—C6 | 0.72 (15) | N1—C7—C10—C11 | −177.99 (9) |
| C4—C5—C6—C7 | −0.44 (15) | C7—C10—C11—C4 | −0.13 (15) |
| C5—C6—C7—C10 | −0.12 (14) | O1—C4—C11—C10 | −179.47 (9) |
| C5—C6—C7—N1 | 178.15 (9) | C5—C4—C11—C10 | −0.44 (15) |
| C8—N1—C7—C6 | 19.69 (15) |
| Cg1 is the centroid of the C4–C11 ring. |
| D—H···A | D—H | H···A | D···A | D—H···A |
| N1—H1···O2i | 0.879 (14) | 1.993 (14) | 2.8695 (11) | 175.2 (13) |
| C6—H6···O2 | 0.95 | 2.31 | 2.8816 (13) | 118 |
| C9—H9B···O2i | 0.98 | 2.53 | 3.4043 (14) | 148 |
| C5—H5···Cg1ii | 0.95 | 2.69 | 3.5171 (12) | 146 |
| C9—H9A···Cg1iii | 0.98 | 2.94 | 3.7373 (12) | 139 |
| Symmetry codes: (i) −x, y−1/2, −z−1/2; (ii) x, −y−1/2, z−1/2; (iii) −x, −y, −z. |
| Cg1 is the centroid of the C4–C11 ring. |
| D—H···A | D—H | H···A | D···A | D—H···A |
| N1—H1···O2i | 0.879 (14) | 1.993 (14) | 2.8695 (11) | 175.2 (13) |
| C9—H9B···O2i | 0.98 | 2.53 | 3.4043 (14) | 148.2 |
| C5—H5···Cg1ii | 0.95 | 2.69 | 3.5171 (12) | 146 |
| C9—H9A···Cg1iii | 0.98 | 2.94 | 3.7373 (12) | 139 |
| Symmetry codes: (i) −x, y−1/2, −z−1/2; (ii) x, −y−1/2, z−1/2; (iii) −x, −y, −z. |
Research funds of the University of Johannesburg and the Research Centre for Synthesis and Catalysis are gratefully acknowledged. Mrs Z. H. Phasha is thanked for the data collection.
Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115–119.
Brandenburg, K. & Putz, H. (2005). DIAMOND. Crystal Impact GbR, Bonn, Germany.
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Hoogendoorn, S., Blom, A. E. M., Willems, L. I., van der Marel, G. A. & Overkleeft, H. S. (2011). Org. Lett. 13, 5656–5659.
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In our pursuit in the development of hybrid drug candidates against tuberculosis, malaria and cancer (Morphy et al., 2004), the title compound was identified as a building starting material. The compound was synthesized by chemoselective N-acetylation of 4-aminophenol followed by reaction with propargyl bromide in the presence of K2CO3 (Hoogendoorn et al., 2011). To confirm the chemoselectivity, herein we report the single-crystal structure of the title compound.
In the crystal structure of the title compound the acetamide and propyn-1-yloxy substituents form dihedral angles to the six-membered ring of 18.31 (6)° and 7.01 (10)° respectively (Figure 1). Molecules are linked by infinite one-dimensional N—H···O hydrogen bonding into chains that elongate in the [010] direction (see Figure 2 for a visual summary).