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Belay, Yonas H.

Kinfe, Henok H.

Muller, Alfred

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University of Johannesburg Institutional Repository

N-[4-(2-Propyn-1-yloxy)phenyl]-acetamideYonas H. Belay, Henok H. Kinfe and Alfred Muller*Research Centre for Synthesis and Catalysis, Department of Chemistry, University ofJohannesburg (APK Campus), PO Box 524, Auckland Park, Johannesburg, 2006,South AfricaCorrespondence e-mail: mullera@uj.ac.zaReceived 28 August 2012; accepted 1 October 2012Key indicators: single-crystal X-ray study; T = 100 K; mean (C–C) = 0.002 A˚;R factor = 0.037; wR factor = 0.100; data-to-parameter ratio = 18.2.The title compound, C11H11NO2, was synthesized by chemo-selective N-acetylation of 4-aminophenol followed by reactionwith propargyl bromide in the presence of K2CO3. theacetamide and propyn-1-yloxy substituents form dihedralangles of 18.31 (6) and 7.01 (10), respectively, with thebenzene ring. In the crystal, molecules are linked by N—H  O hydrogen bonds into chains along [010]. C—H  O andC—H   interactions also occur.Related literatureFor background to the development of hybrid drug candidatesagainst 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).ExperimentalCrystal dataC11H11NO2Mr = 189.21Monoclinic, P21=ca = 13.973 (2) A˚b = 9.1794 (13) A˚c = 7.5105 (11) A˚ = 99.441 (4)V = 950.3 (2) A˚3Z = 4Mo K radiation = 0.09 mm1T = 100 K0.3  0.26  0.23 mmData collectionBruker APEX DUO 4K CCDdiffractometerAbsorption correction: multi-scan(SADABS; Bruker, 2008)Tmin = 0.969, Tmax = 0.9816753 measured reflections2388 independent reflections2103 reflections with I > 2(I)Rint = 0.018RefinementR[F 2 > 2(F 2)] = 0.037wR(F 2) = 0.100S = 1.042388 reflections131 parametersH atoms treated by a mixture ofindependent and constrainedrefinementmax = 0.28 e A˚3min = 0.24 e A˚3Table 1Hydrogen-bond geometry (A˚, ).Cg1 is the centroid of the C4–C11 ring.D—H  A D—H H  A D  A D—H  AN1—H1  O2i 0.879 (14) 1.993 (14) 2.8695 (11) 175.2 (13)C9—H9B  O2i 0.98 2.53 3.4043 (14) 148C5—H5  Cg1ii 0.95 2.69 3.5171 (12) 146C9—H9A  Cg1iii 0.98 2.94 3.7373 (12) 139Symmetry codes: (i) x; y  12;z 12; (ii) x;y 12; z 12; (iii) x;y;z.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); soft-ware used to prepare material for publication: WinGX (Farrugia,1999).Research funds of the University of Johannesburg and theResearch Centre for Synthesis and Catalysis are gratefullyacknowledged. Mrs Z. H. Phasha is thanked for the datacollection.Supplementary data and figures for this paper are available from theIUCr electronic archives (Reference: NC2291).ReferencesAltomare, 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.Bruker (2008). SADABS, SAINT and XPREP. Bruker AXS Inc., Madison,Wisconsin, USA.Bruker (2011). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838.Hoogendoorn, S., Blom, A. E. M., Willems, L. I., van der Marel, G. A. &Overkleeft, H. S. (2011). Org. Lett. 13, 5656–5659.Morphy, R., Kay, C. & Rankovic, Z. (2004). Drug Discov. Today, 9, 641–651.Reppe, W. (1955). Justus Liebigs Ann. Chem. 596, 38–79.Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.organic compoundso3072 Belay et al. doi:10.1107/S1600536812041207 Acta Cryst. (2012). E68, o3072Acta Crystallographica Section EStructure ReportsOnlineISSN 1600-5368supplementary materialssup-1Acta Cryst. (2012). E68, o3072    supplementary materialsActa Cryst. (2012). E68, o3072    [doi:10.1107/S1600536812041207]N-[4-(2-Propyn-1-yloxy)phenyl]acetamideYonas H. Belay, Henok H. Kinfe and Alfred MullerComment 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).Experimental 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).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 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.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).supplementary materialssup-2Acta Cryst. (2012). E68, o3072    Figure 1Crystal structure of the title compound with labeling and displacement ellipsoids drawn at the 50% probability level.. Figure 2Packing 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. supplementary materialssup-3Acta Cryst. (2012). E68, o3072    N-[4-(2-Propyn-1-yloxy)phenyl]acetamide Crystal data C11H11NO2Mr = 189.21Monoclinic, P21/cHall symbol: -P 2ybca = 13.973 (2) Åb = 9.1794 (13) Åc = 7.5105 (11) Åβ = 99.441 (4)°V = 950.3 (2) Å3Z = 4F(000) = 400Dx = 1.323 Mg m−3Mo Kα radiation, λ = 0.71073 ÅCell parameters from 3099 reflectionsθ = 2.7–28.4°µ = 0.09 mm−1T = 100 KBlock, pale yellow0.3 × 0.26 × 0.23 mmData collection Bruker APEX DUO 4K CCD diffractometerGraphite monochromatorDetector resolution: 8.4 pixels mm-1φ and ω scansAbsorption correction: multi-scan (SADABS; Bruker, 2008)Tmin = 0.969, Tmax = 0.9816753 measured reflections2388 independent reflections2103 reflections with I > 2σ(I)Rint = 0.018θmax = 28.5°, θmin = 2.7°h = −18→18k = −12→11l = −10→10Refinement Refinement on F2Least-squares matrix: fullR[F2 > 2σ(F2)] = 0.037wR(F2) = 0.100S = 1.042388 reflections131 parameters0 restraintsPrimary atom site location: structure-invariant direct methodsSecondary atom site location: difference Fourier mapHydrogen site location: inferred from neighbouring sitesH atoms treated by a mixture of independent and constrained refinementw = 1/[σ2(Fo2) + (0.0509P)2 + 0.3049P] where P = (Fo2 + 2Fc2)/3(Δ/σ)max < 0.001Δρmax = 0.28 e Å−3Δρmin = −0.24 e Å−3Special details 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.supplementary materialssup-4Acta Cryst. (2012). E68, o3072    Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) x y z Uiso*/UeqO1 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*Atomic displacement parameters (Å2) U11 U22 U33 U12 U13 U23O1 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)supplementary materialssup-5Acta Cryst. (2012). E68, o3072    Geometric parameters (Å, º) O1—C4 1.3713 (12) C5—C6 1.3965 (14)O1—C3 1.4360 (12) C5—H5 0.95O2—C8 1.2340 (12) C6—C7 1.3911 (13)N1—C8 1.3495 (13) C6—H6 0.95N1—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 0.98C1—H1A 0.95 C9—H9B 0.98C2—C3 1.4582 (15) C9—H9C 0.98C3—H3A 0.99 C10—C11 1.3807 (14)C3—H3B 0.99 C10—H10 0.95C4—C5 1.3903 (14) C11—H11 0.95C4—C11 1.3922 (14)C4—O1—C3 116.86 (8) C5—C6—H6 119.8C8—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 109.5C2—C3—H3A 110.2 C8—C9—H9B 109.5O1—C3—H3B 110.2 H9A—C9—H9B 109.5C2—C3—H3B 110.2 C8—C9—H9C 109.5H3A—C3—H3B 108.5 H9A—C9—H9C 109.5O1—C4—C5 124.98 (9) H9B—C9—H9C 109.5O1—C4—C11 115.11 (9) C11—C10—C7 120.87 (9)C5—C4—C11 119.90 (9) C11—C10—H10 119.6C4—C5—C6 119.98 (9) C7—C10—H10 119.6C4—C5—H5 120 C10—C11—C4 119.94 (9)C6—C5—H5 120 C10—C11—H11 120C7—C6—C5 120.34 (9) C4—C11—H11 120C7—C6—H6 119.8C4—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)supplementary materialssup-6Acta Cryst. (2012). E68, o3072    Hydrogen-bond geometry (Å, º) Cg1 is the centroid of the C4–C11 ring.D—H···A D—H H···A D···A D—H···AN1—H1···O2i 0.879 (14) 1.993 (14) 2.8695 (11) 175.2 (13)C6—H6···O2 0.95 2.31 2.8816 (13) 118C9—H9B···O2i 0.98 2.53 3.4043 (14) 148C5—H5···Cg1ii 0.95 2.69 3.5171 (12) 146C9—H9A···Cg1iii 0.98 2.94 3.7373 (12) 139Symmetry codes: (i) −x, y−1/2, −z−1/2; (ii) x, −y−1/2, z−1/2; (iii) −x, −y, −z.

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

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

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