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Acta Crystallogr Sect E Struct Rep Online. 2010 October 1; 66(Pt 10): o2521.
Published online 2010 September 8. doi:  10.1107/S1600536810035397
PMCID: PMC2983291

N-Benzyl-2-(3-chloro-4-hy­droxy­phen­yl)acetamide

Abstract

The title compound, C15H14ClNO2, was synthesized as part of a project to generate a combinatorial library based on the fungal natural product 2-(3-chloro-4-hy­droxy­phen­yl)acetamide. It crystallizes as non-planar discrete mol­ecules [the peripheral 3-chloro-4-hy­droxy­phenyl and benzyl groups are twisted out of the plane of the central acetamide group, with N—C—C—C and C—C—C—C torsion angles of −58.8 (3) and 65.0 (2)°, respectively] linked by inter­molecular N—H(...)O and O—H(...)O hydrogen bonds.

Related literature

For the preparation and characterization of the title compound, see: Poulsen et al. (2006 [triangle]); Davis et al. (2007 [triangle]). For the biological activity of the title compound, see: Davis et al. (2005 [triangle], 2007 [triangle]). For background to organohalogen natural products, see: Gribble (1996 [triangle]). For related structures having the 3-chloro-4-hy­droxy­phenyl­acetamide moiety, see: Krohn et al. (1992 [triangle]); Davis et al. (2005 [triangle]); Davis & Healy (2008 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2521-scheme1.jpg

Experimental

Crystal data

  • C15H14ClNO2
  • M r = 275.72
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2521-efi1.jpg
  • a = 4.8255 (2) Å
  • b = 10.8520 (5) Å
  • c = 12.7701 (6) Å
  • β = 96.055 (4)°
  • V = 664.99 (5) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.28 mm−1
  • T = 296 K
  • 0.55 × 0.40 × 0.04 mm

Data collection

  • Oxford-Diffraction Gemini S Ultra diffractometer
  • Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010 [triangle]) T min = 0.859, T max = 0.989
  • 4800 measured reflections
  • 2334 independent reflections
  • 1979 reflections with I > 2σ(I)
  • R int = 0.020

Refinement

  • R[F 2 > 2σ(F 2)] = 0.030
  • wR(F 2) = 0.070
  • S = 0.96
  • 2334 reflections
  • 172 parameters
  • 1 restraint
  • H-atom parameters constrained
  • Δρmax = 0.13 e Å−3
  • Δρmin = −0.15 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1098 Friedel pairs
  • Flack parameter: −0.11 (6)

Data collection: CrysAlis CCD (Oxford Diffraction, 2009 [triangle]); cell refinement: CrysAlis RED (Oxford Diffraction, 2009 [triangle]); data reduction: CrysAlis RED; program(s) used to solve structure: SIR97 (Altomare et al., 1999 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]); software used to prepare material for publication: PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810035397/tk2709sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810035397/tk2709Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

We acknowledge financial support of this work by Griffith University, the Queensland University of Technology, the Eskitis Institute for Cell and Mol­ecular Therapies and the Australian Research Council.

supplementary crystallographic information

Comment

The title compound (I) (Fig. 1) was synthesized during the generation of a combinatorial library based on the fungal natural product 3-chloro-4-hydroxyphenylacetamide and was shown to display moderate cytotoxicity towards the human melanoma cell line MM96L and the human prostate cell line DU145 with IC50 values of 72 and 51 µM respectively (Davis et al., 2007). Although many organohalogen natural products have been identified (Gribble, 1996), only three crystal structures on compounds incorporating the 3-chloro-4-hydroxyphenylacetamide moiety have been reported to date (Krohn et al., 1992; Davis et al., 2005; Davis & Healy, 2008).

The present compound crystallizes in the chiral space group P21 as discrete molecules with the central C1—C7—C8(-08)-N1—C9—C10 fragment approximately planar. The peripheral 3-chloro-4-hydroxyphenyl (C1—C7, O4, Cl3) and benzyl (C9—C15) groups are twisted out of the plane of the central acetamide group with N1—C9—C10—C11 and C2—C1—C7—C8 torsion angles of -58.8 (3) and 65.0 (2) °, respectively (Fig. 1). In the crystal lattice the amide (N1) and hydroxy (O4) groups form inter-molecular N—H···O and O—H···O hydrogen bonds with the carbonyl O atoms (O8) at (1 + x, y, z) and (-x - 1, y + 1/2, 1 - z), respectively (Table 1 & Fig. 2).

Experimental

Compound (I) was prepared and analytically and spectroscopically characterized as previously reported (Davis et al., 2007; Poulsen et al., 2006). Crystals suitable for X-ray diffraction studies were obtained by recrystallization from a solution of the compound in a solvent mix of 90% methanol, 10% water, and 0.1% trifluoroacetic acid.

Refinement

The carbon-bound H atoms were constrained as riding atoms with C—H = 0.93–0.96 Å. The amide and hydroxyl protons were located in difference Fourier maps and constrained with N—H 0.86 Å and O—H = 0.90 Å in the final refinement. Uiso(H) values were set at 1.2Ueq of the parent atom.

Figures

Fig. 1.
View of (I) with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 30% probability level.
Fig. 2.
View down the crystallographic b axis of the hydrogen bonding arrangement (dashed lines) and crystal packing for (I).

Crystal data

C15H14ClNO2F(000) = 288
Mr = 275.72Dx = 1.377 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71070 Å
Hall symbol: P 2ybCell parameters from 2771 reflections
a = 4.8255 (2) Åθ = 3.2–32.2°
b = 10.8520 (5) ŵ = 0.28 mm1
c = 12.7701 (6) ÅT = 296 K
β = 96.055 (4)°Plate, colourless
V = 664.99 (5) Å30.55 × 0.40 × 0.04 mm
Z = 2

Data collection

Oxford-Diffraction Gemini S Ultra diffractometer2334 independent reflections
Radiation source: Enhance (Mo) X-ray Source1979 reflections with I > 2σ(I)
graphiteRint = 0.020
Detector resolution: 16.0774 pixels mm-1θmax = 25.0°, θmin = 3.2°
ω and [var phi] scansh = −5→5
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010)k = −12→12
Tmin = 0.859, Tmax = 0.989l = −15→12
4800 measured reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.030H-atom parameters constrained
wR(F2) = 0.070w = 1/[σ2(Fo2) + (0.0444P)2] where P = (Fo2 + 2Fc2)/3
S = 0.96(Δ/σ)max = 0.002
2334 reflectionsΔρmax = 0.13 e Å3
172 parametersΔρmin = −0.15 e Å3
1 restraintAbsolute structure: Flack (1983), 1098 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: −0.11 (6)

Special details

Experimental. CrysAlisPro (Oxford Diffraction, 2010). Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.
Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles
Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2 > σ(F2) is used only for calculating -R-factor-obs 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)

xyzUiso*/Ueq
Cl3−0.22153 (16)0.10603 (6)0.70233 (4)0.0799 (3)
O4−0.5174 (3)0.33833 (14)0.69050 (12)0.0612 (6)
O8−0.3412 (2)0.08182 (14)0.27899 (10)0.0506 (5)
N10.0633 (3)0.05425 (16)0.21183 (12)0.0452 (5)
C1−0.1150 (4)0.25973 (19)0.42574 (15)0.0386 (6)
C2−0.1047 (4)0.1808 (2)0.51082 (16)0.0449 (7)
C3−0.2387 (4)0.20842 (19)0.59745 (15)0.0452 (7)
C4−0.3886 (4)0.31713 (18)0.60254 (15)0.0431 (7)
C5−0.3982 (4)0.39584 (19)0.51848 (17)0.0480 (7)
C6−0.2645 (4)0.36758 (19)0.43020 (16)0.0469 (7)
C70.0273 (4)0.2253 (2)0.33001 (16)0.0462 (7)
C8−0.0977 (3)0.1137 (2)0.27214 (13)0.0366 (6)
C9−0.0319 (5)−0.0518 (2)0.14734 (18)0.0568 (8)
C100.1377 (4)−0.06951 (19)0.05671 (16)0.0412 (7)
C110.1558 (4)0.0217 (2)−0.01686 (18)0.0577 (8)
C120.3073 (5)0.0053 (2)−0.10153 (19)0.0663 (9)
C130.4390 (5)−0.1045 (3)−0.11432 (19)0.0643 (9)
C140.4229 (5)−0.1963 (2)−0.04274 (19)0.0660 (9)
C150.2735 (5)−0.1792 (2)0.04367 (18)0.0531 (8)
H10.231700.078400.209900.0540*
H2−0.004400.105900.509300.0540*
H4−0.564400.419100.700500.0730*
H5−0.499400.470800.520800.0570*
H6−0.273800.422900.372900.0580*
H110.061900.09810−0.008300.0710*
H120.316400.06970−0.151800.0840*
H130.54640−0.11580−0.170200.0790*
H140.50880−0.27320−0.052000.0800*
H150.26570−0.242600.093800.0660*
H710.015800.293200.283100.0550*
H720.217600.208100.352600.0550*
H91−0.22280−0.039500.121100.0690*
H92−0.01890−0.123900.190400.0690*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl30.1357 (6)0.0590 (4)0.0499 (3)0.0134 (4)0.0333 (3)0.0106 (3)
O40.0733 (10)0.0631 (10)0.0523 (9)0.0062 (8)0.0312 (8)−0.0102 (8)
O80.0325 (6)0.0649 (11)0.0572 (8)−0.0121 (6)0.0183 (6)−0.0131 (7)
N10.0279 (7)0.0588 (11)0.0510 (10)−0.0130 (7)0.0142 (7)−0.0190 (9)
C10.0343 (9)0.0426 (11)0.0406 (11)−0.0076 (8)0.0115 (8)−0.0073 (9)
C20.0506 (11)0.0393 (12)0.0464 (12)0.0077 (9)0.0128 (9)−0.0042 (10)
C30.0564 (12)0.0425 (11)0.0382 (11)−0.0023 (9)0.0124 (10)−0.0009 (9)
C40.0439 (11)0.0464 (12)0.0409 (11)0.0001 (9)0.0140 (9)−0.0086 (10)
C50.0495 (12)0.0446 (12)0.0515 (13)0.0108 (9)0.0133 (10)−0.0059 (11)
C60.0550 (12)0.0431 (12)0.0440 (12)−0.0021 (10)0.0122 (10)−0.0004 (10)
C70.0428 (10)0.0524 (13)0.0468 (11)−0.0101 (10)0.0201 (9)−0.0079 (10)
C80.0304 (9)0.0481 (11)0.0325 (9)−0.0038 (9)0.0095 (7)0.0021 (9)
C90.0489 (12)0.0657 (15)0.0591 (14)−0.0192 (10)0.0209 (11)−0.0221 (12)
C100.0353 (10)0.0465 (13)0.0426 (11)−0.0105 (9)0.0075 (8)−0.0099 (10)
C110.0580 (13)0.0485 (14)0.0683 (16)0.0089 (11)0.0151 (12)0.0015 (12)
C120.0759 (16)0.0680 (17)0.0571 (15)−0.0015 (13)0.0172 (13)0.0140 (13)
C130.0702 (15)0.0805 (19)0.0456 (13)−0.0025 (13)0.0221 (11)−0.0122 (13)
C140.0833 (18)0.0581 (16)0.0593 (15)0.0144 (12)0.0209 (13)−0.0156 (13)
C150.0693 (14)0.0426 (13)0.0482 (12)−0.0012 (10)0.0099 (10)−0.0025 (10)

Geometric parameters (Å, °)

Cl3—C31.736 (2)C10—C111.374 (3)
O4—C41.360 (2)C11—C121.379 (3)
O8—C81.2368 (18)C12—C131.368 (4)
O4—H40.9200C13—C141.360 (4)
N1—C81.319 (2)C14—C151.393 (3)
N1—C91.461 (3)C2—H20.9500
N1—H10.8600C5—H50.9500
C1—C71.511 (3)C6—H60.9400
C1—C61.379 (3)C7—H710.9500
C1—C21.380 (3)C7—H720.9500
C2—C31.372 (3)C9—H910.9600
C3—C41.389 (3)C9—H920.9500
C4—C51.369 (3)C11—H110.9600
C5—C61.391 (3)C12—H120.9500
C7—C81.511 (3)C13—H130.9300
C9—C101.499 (3)C14—H140.9400
C10—C151.377 (3)C15—H150.9400
Cl3···O42.8932 (17)H1···O8vii2.1500
Cl3···C12i3.554 (2)H1···C112.9500
Cl3···H12ii3.0800H1···H722.3100
Cl3···H12i3.0600H1···H4viii2.5500
Cl3···H15iii3.1000H2···C83.0200
O4···Cl32.8932 (17)H2···C5viii3.0400
O4···O8iv2.767 (2)H2···C6viii2.9600
O4···C9iv3.375 (3)H4···H52.4100
O4···C9iii3.403 (3)H4···O8iv1.8500
O8···O4v2.767 (2)H4···N1iii2.9500
O8···N1vi2.9262 (18)H4···C8iv2.7100
O8···C23.242 (2)H4···C9iv2.9100
O4···H92iii2.8900H4···H1iii2.5500
O4···H92iv2.8600H5···H42.4100
O8···H72vi2.7800H5···C2iv2.9700
O8···H912.5200H6···H712.3600
O8···H1vi2.1500H11···N12.8500
O8···H4v1.8500H11···C15xii2.9200
N1···O8vii2.9262 (18)H11···H14x2.5500
N1···H112.8500H11···H15xii2.5100
N1···H4viii2.9500H12···Cl3ix3.0600
C2···O83.242 (2)H12···Cl3xiii3.0800
C9···O4viii3.403 (3)H14···C11xiv2.8400
C9···O4v3.375 (3)H14···H11xiv2.5500
C12···Cl3ix3.554 (2)H15···H922.3300
C2···H5v2.9700H15···Cl3viii3.1000
C5···H2iii3.0400H15···H11xi2.5100
C6···H2iii2.9600H71···H62.3600
C8···H4v2.7100H72···O8vii2.7800
C8···H23.0200H72···H12.3100
C9···H4v2.9100H91···O82.5200
C11···H12.9500H91···C14vi3.0700
C11···H14x2.8400H91···C15vi2.9500
C14···H91vii3.0700H92···H152.3300
C15···H91vii2.9500H92···O4v2.8600
C15···H11xi2.9200H92···O4viii2.8900
C4—O4—H4115.00C10—C15—C14120.2 (2)
C8—N1—C9123.03 (16)C1—C2—H2119.00
C8—N1—H1119.00C3—C2—H2119.00
C9—N1—H1118.00C4—C5—H5119.00
C2—C1—C6118.01 (18)C6—C5—H5120.00
C2—C1—C7120.12 (18)C1—C6—H6119.00
C6—C1—C7121.85 (18)C5—C6—H6120.00
C1—C2—C3121.21 (19)C1—C7—H71109.00
C2—C3—C4121.02 (19)C1—C7—H72108.00
Cl3—C3—C2119.61 (16)C8—C7—H71109.00
Cl3—C3—C4119.37 (15)C8—C7—H72108.00
O4—C4—C3117.91 (17)H71—C7—H72110.00
O4—C4—C5124.18 (18)N1—C9—H91109.00
C3—C4—C5117.91 (18)N1—C9—H92109.00
C4—C5—C6121.19 (19)C10—C9—H91109.00
C1—C6—C5120.66 (19)C10—C9—H92109.00
C1—C7—C8113.70 (16)H91—C9—H92109.00
O8—C8—C7121.53 (16)C10—C11—H11119.00
O8—C8—N1121.81 (18)C12—C11—H11120.00
N1—C8—C7116.64 (15)C11—C12—H12120.00
N1—C9—C10111.81 (18)C13—C12—H12120.00
C9—C10—C11121.00 (19)C12—C13—H13121.00
C9—C10—C15120.65 (19)C14—C13—H13120.00
C11—C10—C15118.33 (19)C13—C14—H14120.00
C10—C11—C12121.4 (2)C15—C14—H14119.00
C11—C12—C13119.8 (2)C10—C15—H15120.00
C12—C13—C14119.8 (2)C14—C15—H15120.00
C13—C14—C15120.4 (2)
C8—N1—C9—C10156.64 (18)C3—C4—C5—C60.6 (3)
C9—N1—C8—O81.0 (3)O4—C4—C5—C6−179.11 (18)
C9—N1—C8—C7−177.14 (17)C4—C5—C6—C1−0.9 (3)
C6—C1—C2—C30.0 (3)C1—C7—C8—O823.7 (3)
C7—C1—C2—C3−178.18 (18)C1—C7—C8—N1−158.08 (17)
C2—C1—C6—C50.6 (3)N1—C9—C10—C11−58.8 (3)
C6—C1—C7—C8−113.1 (2)N1—C9—C10—C15122.9 (2)
C2—C1—C7—C865.0 (2)C9—C10—C15—C14177.8 (2)
C7—C1—C6—C5178.69 (18)C11—C10—C15—C14−0.5 (3)
C1—C2—C3—C4−0.2 (3)C9—C10—C11—C12−178.8 (2)
C1—C2—C3—Cl3179.67 (16)C15—C10—C11—C12−0.5 (3)
Cl3—C3—C4—O4−0.2 (3)C10—C11—C12—C131.2 (3)
C2—C3—C4—C5−0.1 (3)C11—C12—C13—C14−0.9 (4)
Cl3—C3—C4—C5−179.95 (15)C12—C13—C14—C15−0.1 (4)
C2—C3—C4—O4179.67 (18)C13—C14—C15—C100.8 (4)

Symmetry codes: (i) x, y, z+1; (ii) x−1, y, z+1; (iii) −x, y+1/2, −z+1; (iv) −x−1, y+1/2, −z+1; (v) −x−1, y−1/2, −z+1; (vi) x−1, y, z; (vii) x+1, y, z; (viii) −x, y−1/2, −z+1; (ix) x, y, z−1; (x) −x+1, y+1/2, −z; (xi) −x, y−1/2, −z; (xii) −x, y+1/2, −z; (xiii) x+1, y, z−1; (xiv) −x+1, y−1/2, −z.

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O8vii0.862.152.9262 (18)150
O4—H4···O8iv0.921.852.767 (2)180

Symmetry codes: (vii) x+1, y, z; (iv) −x−1, y+1/2, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: TK2709).

References

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