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

Rohan A Davis; Peter C Healy

doi:10.1107/S1600536810035397

. 2010 Sep 8;66(Pt 10):o2521. doi: 10.1107/S1600536810035397

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

Rohan A Davis ^a, Peter C Healy ^b,^*

PMCID: PMC2983291 PMID: 21587515

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

Experimental

Crystal data

C₁₅H₁₄ClNO₂
M _r = 275.72
Monoclinic,
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 ▶) 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
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.15 e Å⁻³
Absolute structure: Flack (1983 ▶), 1098 Friedel pairs
Flack parameter: −0.11 (6)

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

Supplementary Material

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

e-66-o2521-sup1.cif^{(20KB, cif)}

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

e-66-o2521-Isup2.hkl^{(114.7KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O8ⁱ	0.86	2.15	2.9262 (18)	150
O4—H4⋯O8ⁱⁱ	0.92	1.85	2.767 (2)	180

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Symmetry codes: (i) Inline graphic ; (ii) .

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.