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

Belay, Y.H.; Kinfe, H.H.; Muller, A.

doi:10.1107/S1600536812041207

organic compounds

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Volume 68| Part 11| November 2012| Page o3072

doi:10.1107/S1600536812041207

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

Yonas H. Belay,^a Henok H. Kinfe ^a and Alfred Muller ^a ^*

^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 ). For details of the synthesis of the title compound, see: Hoogendoorn et al. (2011 ); Reppe (1955 ).

Experimental

Crystal data

C₁₁H₁₁NO₂
M_r = 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 ) T_min = 0.969, T_max = 0.981
6753 measured reflections
2388 independent reflections
2103 reflections with I > 2σ(I)
R_int = 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
Δρ_max = 0.28 e Å⁻³
Δρ_min = −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	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
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) $[-x, y-{\script{1\over 2}}, -z-{\script{1\over 2}}]$ ; (ii) $[x, -y-{\script{1\over 2}}, z-{\script{1\over 2}}]$ ; (iii) -x, -y, -z.

Data collection: APEX2 (Bruker, 2011 ); 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 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536812041207/nc2291sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812041207/nc2291Isup2.hkl

checkCIF report

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).

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

	Fig. 1. Crystal structure of the title compound with labeling and displacement ellipsoids drawn at the 50% probability level..
	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

C₁₁H₁₁NO₂	F(000) = 400
M_r = 189.21	D_x = 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

Data collection top

Bruker APEX DUO 4K CCD diffractometer	2388 independent reflections
Graphite monochromator	2103 reflections with I > 2σ(I)
Detector resolution: 8.4 pixels mm^-1	R_int = 0.018
ϕ and ω scans	θ_max = 28.5°, θ_min = 2.7°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −18→18
T_min = 0.969, T_max = 0.981	k = −12→11
6753 measured reflections	l = −10→10

Refinement top

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(F_o²) + (0.0509P)² + 0.3049P] where P = (F_o² + 2F_c²)/3
2388 reflections	(Δ/σ)_max < 0.001
131 parameters	Δρ_max = 0.28 e Å⁻³
0 restraints	Δρ_min = −0.24 e Å⁻³

Crystal data top

C₁₁H₁₁NO₂	V = 950.3 (2) Å³
M_r = 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)°

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)
T_min = 0.969, T_max = 0.981	R_int = 0.018
6753 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	0 restraints
wR(F²) = 0.100	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	Δρ_max = 0.28 e Å⁻³
2388 reflections	Δρ_min = −0.24 e Å⁻³
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

	x	y	z	U_iso*/U_eq
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*

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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.

Experimental details

Crystal data
Chemical formula	C₁₁H₁₁NO₂
M_r	189.21
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	100
a, b, c (Å)	13.973 (2), 9.1794 (13), 7.5105 (11)
β (°)	99.441 (4)
V (Å³)	950.3 (2)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.3 × 0.26 × 0.23

Data collection
Diffractometer	Bruker APEX DUO 4K CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2008)
T_min, T_max	0.969, 0.981
No. of measured, independent and observed [I > 2σ(I)] reflections	6753, 2388, 2103
R_int	0.018
(sin θ/λ)_max (Å⁻¹)	0.671

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.100, 1.04
No. of reflections	2388
No. of parameters	131
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	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···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.

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

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. Web of Science CrossRef CAS IUCr Journals Google Scholar
Brandenburg, K. & Putz, H. (2005). DIAMOND. Crystal Impact GbR, Bonn, Germany. Google Scholar
Bruker (2008). SADABS, SAINT and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2011). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Hoogendoorn, 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 Google Scholar
Morphy, R., Kay, C. & Rankovic, Z. (2004). Drug Discov. Today, 9, 641–651. Web of Science CrossRef PubMed CAS Google Scholar
Reppe, W. (1955). Justus Liebigs Ann. Chem. 596, 38–79. CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

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