organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

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

aResearch Centre for Synthesis and Catalysis, Department of Chemistry, University of Johannesburg (APK Campus), PO Box 524, Auckland Park, Johannesburg, 2006, South Africa
*Correspondence e-mail: mullera@uj.ac.za

(Received 28 August 2012; accepted 1 October 2012; online 6 October 2012)

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[Morphy, R., Kay, C. & Rankovic, Z. (2004). Drug Discov. Today, 9, 641-651.]). For details of the synthesis of the title compound, see: Hoogendoorn et al. (2011[Hoogendoorn, S., Blom, A. E. M., Willems, L. I., van der Marel, G. A. & Overkleeft, H. S. (2011). Org. Lett. 13, 5656-5659.]); Reppe (1955[Reppe, W. (1955). Justus Liebigs Ann. Chem. 596, 38-79.]).

[Scheme 1]

Experimental

Crystal data
  • C11H11NO2

  • Mr = 189.21

  • Monoclinic, P 21 /c

  • a = 13.973 (2) Å

  • b = 9.1794 (13) Å

  • c = 7.5105 (11) Å

  • β = 99.441 (4)°

  • V = 950.3 (2) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.09 mm−1

  • T = 100 K

  • 0.3 × 0.26 × 0.23 mm

Data collection
  • Bruker APEX DUO 4K CCD diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2008[Bruker (2008). SADABS, SAINT and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.969, Tmax = 0.981

  • 6753 measured reflections

  • 2388 independent reflections

  • 2103 reflections with I > 2σ(I)

  • Rint = 0.018

Refinement
  • R[F2 > 2σ(F2)] = 0.037

  • wR(F2) = 0.100

  • S = 1.04

  • 2388 reflections

  • 131 parameters

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.28 e Å−3

  • Δρmin = −0.24 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the C4–C11 ring.

D—H⋯A D—H H⋯A DA 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
C5—H5⋯Cg1ii 0.95 2.69 3.5171 (12) 146
C9—H9ACg1iii 0.98 2.94 3.7373 (12) 139
Symmetry codes: (i) [-x, y-{\script{1\over 2}}, -z-{\script{1\over 2}}]; (ii) [x, -y-{\script{1\over 2}}, z-{\script{1\over 2}}]; (iii) -x, -y, -z.

Data collection: APEX2 (Bruker, 2011[Bruker (2011). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2008[Bruker (2008). SADABS, SAINT and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT and XPREP (Bruker, 2008[Bruker (2008). SADABS, SAINT and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA.]); program(s) used to solve structure: SIR97 (Altomare et al., 1999[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.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: DIAMOND (Brandenburg & Putz, 2005[Brandenburg, K. & Putz, H. (2005). DIAMOND. Crystal Impact GbR, Bonn, Germany.]); software used to prepare material for publication: WinGX (Farrugia, 1999[Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837-838.]).

Supporting information


Comment top

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).

Related literature top

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).

Experimental top

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 top

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 top

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).

Figures top
[Figure 1] Fig. 1. Crystal structure of the title compound with labeling and displacement ellipsoids drawn at the 50% probability level..
[Figure 2] 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.
N-[4-(2-Propyn-1-yloxy)phenyl]acetamide top
Crystal data top
C11H11NO2F(000) = 400
Mr = 189.21Dx = 1.323 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 3099 reflections
a = 13.973 (2) Åθ = 2.7–28.4°
b = 9.1794 (13) ŵ = 0.09 mm1
c = 7.5105 (11) ÅT = 100 K
β = 99.441 (4)°Block, pale yellow
V = 950.3 (2) Å30.3 × 0.26 × 0.23 mm
Z = 4
Data collection top
Bruker APEX DUO 4K CCD
diffractometer
2388 independent reflections
Graphite monochromator2103 reflections with I > 2σ(I)
Detector resolution: 8.4 pixels mm-1Rint = 0.018
ϕ and ω scansθmax = 28.5°, θmin = 2.7°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 1818
Tmin = 0.969, Tmax = 0.981k = 1211
6753 measured reflectionsl = 1010
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.037Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.100H 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 parametersΔρmax = 0.28 e Å3
0 restraintsΔρmin = 0.24 e Å3
Crystal data top
C11H11NO2V = 950.3 (2) Å3
Mr = 189.21Z = 4
Monoclinic, P21/cMo Kα radiation
a = 13.973 (2) ŵ = 0.09 mm1
b = 9.1794 (13) ÅT = 100 K
c = 7.5105 (11) Å0.3 × 0.26 × 0.23 mm
β = 99.441 (4)°
Data collection top
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 = 0.981Rint = 0.018
6753 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0370 restraints
wR(F2) = 0.100H atoms treated by a mixture of independent and constrained refinement
S = 1.04Δρmax = 0.28 e Å3
2388 reflectionsΔρmin = 0.24 e Å3
131 parameters
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.44065 (5)0.09706 (8)0.16260 (10)0.01982 (18)
O20.00853 (5)0.27539 (8)0.14889 (10)0.02019 (18)
N10.05791 (6)0.05346 (9)0.18684 (12)0.01555 (19)
C10.63468 (9)0.09825 (14)0.49415 (17)0.0288 (3)
H1A0.69430.06410.56010.035*
C20.56036 (8)0.14084 (12)0.41199 (15)0.0215 (2)
C30.46720 (8)0.19131 (12)0.31532 (14)0.0202 (2)
H3A0.41740.18740.3950.024*
H3B0.47260.29310.27480.024*
C40.34482 (7)0.09626 (11)0.08432 (13)0.0160 (2)
C50.27561 (7)0.19574 (11)0.12113 (13)0.0165 (2)
H50.29340.27120.20680.02*
C60.17996 (7)0.18471 (11)0.03218 (13)0.0160 (2)
H60.13270.25240.05820.019*
C70.15352 (7)0.07514 (10)0.09429 (13)0.0143 (2)
C80.01572 (7)0.15035 (11)0.20997 (13)0.0156 (2)
C90.10956 (7)0.09587 (11)0.31599 (14)0.0192 (2)
H9A0.16050.10050.24070.029*
H9B0.10140.00510.3530.029*
H9C0.12790.15680.42330.029*
C100.22426 (7)0.02335 (11)0.13094 (14)0.0169 (2)
H100.2070.09820.21770.02*
C110.31883 (7)0.01321 (11)0.04271 (14)0.0175 (2)
H110.36610.08090.06870.021*
H10.0464 (10)0.0325 (16)0.2373 (18)0.021*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0138 (4)0.0255 (4)0.0184 (4)0.0032 (3)0.0024 (3)0.0051 (3)
O20.0192 (4)0.0149 (3)0.0248 (4)0.0026 (3)0.0015 (3)0.0008 (3)
N10.0139 (4)0.0124 (4)0.0192 (4)0.0008 (3)0.0006 (3)0.0010 (3)
C10.0196 (6)0.0338 (6)0.0302 (6)0.0025 (5)0.0039 (5)0.0011 (5)
C20.0192 (5)0.0236 (5)0.0211 (5)0.0036 (4)0.0014 (4)0.0027 (4)
C30.0190 (5)0.0213 (5)0.0189 (5)0.0002 (4)0.0010 (4)0.0032 (4)
C40.0136 (5)0.0190 (5)0.0148 (4)0.0012 (4)0.0000 (4)0.0021 (3)
C50.0168 (5)0.0165 (4)0.0154 (4)0.0005 (4)0.0003 (4)0.0022 (3)
C60.0162 (5)0.0150 (4)0.0168 (5)0.0020 (4)0.0022 (4)0.0000 (3)
C70.0140 (5)0.0138 (4)0.0146 (4)0.0001 (3)0.0007 (3)0.0027 (3)
C80.0146 (5)0.0156 (4)0.0162 (4)0.0001 (3)0.0014 (4)0.0032 (3)
C90.0147 (5)0.0184 (5)0.0234 (5)0.0007 (4)0.0006 (4)0.0018 (4)
C100.0181 (5)0.0139 (4)0.0179 (5)0.0004 (4)0.0006 (4)0.0017 (3)
C110.0171 (5)0.0159 (4)0.0191 (5)0.0040 (4)0.0016 (4)0.0002 (4)
Geometric parameters (Å, º) top
O1—C41.3713 (12)C5—C61.3965 (14)
O1—C31.4360 (12)C5—H50.95
O2—C81.2340 (12)C6—C71.3911 (13)
N1—C81.3495 (13)C6—H60.95
N1—C71.4152 (13)C7—C101.3999 (14)
N1—H10.879 (14)C8—C91.5036 (14)
C1—C21.1840 (17)C9—H9A0.98
C1—H1A0.95C9—H9B0.98
C2—C31.4582 (15)C9—H9C0.98
C3—H3A0.99C10—C111.3807 (14)
C3—H3B0.99C10—H100.95
C4—C51.3903 (14)C11—H110.95
C4—C111.3922 (14)
C4—O1—C3116.86 (8)C5—C6—H6119.8
C8—N1—C7127.50 (9)C6—C7—C10118.96 (9)
C8—N1—H1117.0 (9)C6—C7—N1124.10 (9)
C7—N1—H1115.5 (9)C10—C7—N1116.92 (9)
C2—C1—H1A180O2—C8—N1123.46 (9)
C1—C2—C3178.14 (12)O2—C8—C9121.13 (9)
O1—C3—C2107.39 (8)N1—C8—C9115.41 (9)
O1—C3—H3A110.2C8—C9—H9A109.5
C2—C3—H3A110.2C8—C9—H9B109.5
O1—C3—H3B110.2H9A—C9—H9B109.5
C2—C3—H3B110.2C8—C9—H9C109.5
H3A—C3—H3B108.5H9A—C9—H9C109.5
O1—C4—C5124.98 (9)H9B—C9—H9C109.5
O1—C4—C11115.11 (9)C11—C10—C7120.87 (9)
C5—C4—C11119.90 (9)C11—C10—H10119.6
C4—C5—C6119.98 (9)C7—C10—H10119.6
C4—C5—H5120C10—C11—C4119.94 (9)
C6—C5—H5120C10—C11—H11120
C7—C6—C5120.34 (9)C4—C11—H11120
C7—C6—H6119.8
C4—O1—C3—C2161.20 (9)C8—N1—C7—C10162.01 (10)
C3—O1—C4—C511.37 (14)C7—N1—C8—O20.68 (16)
C3—O1—C4—C11169.65 (9)C7—N1—C8—C9179.68 (9)
O1—C4—C5—C6179.65 (9)C6—C7—C10—C110.40 (15)
C11—C4—C5—C60.72 (15)N1—C7—C10—C11177.99 (9)
C4—C5—C6—C70.44 (15)C7—C10—C11—C40.13 (15)
C5—C6—C7—C100.12 (14)O1—C4—C11—C10179.47 (9)
C5—C6—C7—N1178.15 (9)C5—C4—C11—C100.44 (15)
C8—N1—C7—C619.69 (15)
Hydrogen-bond geometry (Å, º) top
Cg1 is the centroid of the C4–C11 ring.
D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.879 (14)1.993 (14)2.8695 (11)175.2 (13)
C6—H6···O20.952.312.8816 (13)118
C9—H9B···O2i0.982.533.4043 (14)148
C5—H5···Cg1ii0.952.693.5171 (12)146
C9—H9A···Cg1iii0.982.943.7373 (12)139
Symmetry codes: (i) x, y1/2, z1/2; (ii) x, y1/2, z1/2; (iii) x, y, z.

Experimental details

Crystal data
Chemical formulaC11H11NO2
Mr189.21
Crystal system, space groupMonoclinic, P21/c
Temperature (K)100
a, b, c (Å)13.973 (2), 9.1794 (13), 7.5105 (11)
β (°) 99.441 (4)
V3)950.3 (2)
Z4
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.3 × 0.26 × 0.23
Data collection
DiffractometerBruker APEX DUO 4K CCD
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2008)
Tmin, Tmax0.969, 0.981
No. of measured, independent and
observed [I > 2σ(I)] reflections
6753, 2388, 2103
Rint0.018
(sin θ/λ)max1)0.671
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.037, 0.100, 1.04
No. of reflections2388
No. of parameters131
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.28, 0.24

Computer programs: APEX2 (Bruker, 2011), SAINT (Bruker, 2008), SAINT and XPREP (Bruker, 2008), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), DIAMOND (Brandenburg & Putz, 2005), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top
Cg1 is the centroid of the C4–C11 ring.
D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.879 (14)1.993 (14)2.8695 (11)175.2 (13)
C9—H9B···O2i0.982.533.4043 (14)148.2
C5—H5···Cg1ii0.952.693.5171 (12)146
C9—H9A···Cg1iii0.982.943.7373 (12)139
Symmetry codes: (i) x, y1/2, z1/2; (ii) x, y1/2, z1/2; (iii) x, y, z.
 

Acknowledgements

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.

References

First citationAltomare, 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.  Web of Science CrossRef CAS IUCr Journals
First citationBrandenburg, K. & Putz, H. (2005). DIAMOND. Crystal Impact GbR, Bonn, Germany.
First citationBruker (2008). SADABS, SAINT and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationBruker (2011). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationFarrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838.  CrossRef CAS IUCr Journals
First citationHoogendoorn, S., Blom, A. E. M., Willems, L. I., van der Marel, G. A. & Overkleeft, H. S. (2011). Org. Lett. 13, 5656–5659.  Web of Science CrossRef CAS PubMed
First citationMorphy, R., Kay, C. & Rankovic, Z. (2004). Drug Discov. Today, 9, 641–651.  Web of Science CrossRef PubMed CAS
First citationReppe, W. (1955). Justus Liebigs Ann. Chem. 596, 38–79.  CrossRef CAS
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals

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.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds