N-[4-(2-Propyn-1-yloxy)phenyl]acetamide

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—H⋯O and C—H⋯π interactions also occur.


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); Reppe (1955). H atoms treated by a mixture of independent and constrained refinement Á max = 0.28 e Å À3 Á min = À0.24 e Å À3 Table 1 Hydrogen-bond geometry (Å , ).

Yonas H. Belay, Henok H. Kinfe and Alfred Muller Comment
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 K 2 CO 3 (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).

Experimental
A solution of N-(hydoxy-phenyl)acetamide (450 mg, 2.980 mmol), synthesized by chemoselective acetylation of 4aminophenol 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).

Refinement
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 U iso (H) = 1.2U eq , except for methyl and amide hydrogen atoms where U iso (H) = 1.5U eq was utilized. The initial positions of methyl hydrogen atoms were located from a Fourier difference map and refined as a fixed rotor.

Computing details
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).  Crystal structure of the title compound with labeling and displacement ellipsoids drawn at the 50% probability level..  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 F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. Hydrogen-bond geometry (Å, º) Cg1 is the centroid of the C4-C11 ring. Symmetry codes: (i) −x, y−1/2, −z−1/2; (ii) x, −y−1/2, z−1/2; (iii) −x, −y, −z.