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Acta Crystallogr Sect E Struct Rep Online. 2008 June 1; 64(Pt 6): o1057.
Published online 2008 May 10. doi:  10.1107/S1600536808013299
PMCID: PMC2961350

2-(3-Chloro-4-hydroxy­phen­yl)-N-(3,4-dimethoxy­pheneth­yl)acetamide

Abstract

The title compound, C18H20ClNO4, was synthesized during the generation of a combinatorial library based on the fungal natural product 3-chloro-4-hydroxy­phenyl­acetamide. It crystallizes as discrete mol­ecules linked by inter­molecular C(9) chains of N—H(...)O and O—H(...)O hydrogen bonds which in turn combine to form chains of R 2 2(20) rings.

Related literature

For related literature, see: Bernstein et al. (1995 [triangle]); Davis et al. (2005 [triangle], 2007 [triangle]).

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Object name is e-64-o1057-scheme1.jpg

Experimental

Crystal data

  • C18H20ClNO4
  • M r = 349.80
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1057-efi1.jpg
  • a = 12.329 (3) Å
  • b = 12.839 (5) Å
  • c = 11.062 (3) Å
  • β = 92.18 (2)°
  • V = 1749.8 (9) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.24 mm−1
  • T = 295 K
  • 0.35 × 0.35 × 0.15 mm

Data collection

  • Rigaku AFC-7R diffractometer
  • Absorption correction: none
  • 3463 measured reflections
  • 3078 independent reflections
  • 1596 reflections with I > 2σ(I)
  • R int = 0.034
  • 3 standard reflections every 150 reflections intensity decay: 0.2%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.056
  • wR(F 2) = 0.165
  • S = 0.99
  • 3078 reflections
  • 217 parameters
  • H-atom parameters constrained
  • Δρmax = 0.21 e Å−3
  • Δρmin = −0.31 e Å−3

Data collection: MSC/AFC7 Diffractometer Control for Windows (Molecular Structure Corporation, 1999 [triangle]); cell refinement: MSC/AFC7 Diffractometer Control for Windows; data reduction: TEXSAN for Windows (Molecular Structure Corporation, 2001 [triangle]); program(s) used to solve structure: TEXSAN for Windows; program(s) used to refine structure: TEXSAN for Windows and SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 (Farrugia, 1997 [triangle]); software used to prepare material for publication: TEXSAN for Windows and PLATON (Spek, 2003 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808013299/tk2268sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808013299/tk2268Isup2.hkl

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

Acknowledgments

We acknowledge financial support of this work by Griffith University and the Eskitis Institute for Cell and Molecular Therapies.

supplementary crystallographic information

Comment

The title compound (I) was synthesized during the generation of a combinatorial library based on the fungal natural product 3-chloro-4-hydroxyphenylacetamide (Davis et al., 2005, 2007). Compound (I) was shown to display moderate cytotoxicity towards the human melanoma cell line MM96L with 94% inhibition at 100 µg ml-1 (Davis et al., 2007).

This compound crystallizes as discrete molecules with three planar components: the acetamide group (C7—C8(O8)—N1—C9), the 3-chloro-4-hydroxyphenyl group (C1—C7, O4, Cl3), and the 3,4-dimethoxybenzyl group (C11—C16, C10, O13—C17, O14—C18), Fig. 1. The C9—C10—C11—C16 and C2—C1—C7—C8 torsion angles are -91.8 (4)° and-78.9 (4)° respectively. In the crystal structure the amide (N1) and hydroxy (O4) groups form C(9) chains (Bernstein et al., 1995) of intermolecular N—H···O and O—H···O hydrogen bonds with the methoxy oxygen (O14) and the carbonyl oxygen (O8), respectively (Table 1) which in turn combine to form chains of R22(20) rings (Fig. 2).

Experimental

Compound (I) was prepared as previously reported (Davis et al., 2007). Crystals suitable for X-ray diffraction studies were obtained by slow evaporation of a n-hexane/ethyl acetate (1:1) solution of (I); m.p. 421–423 K.

Refinement

The carbon-bound H atoms were constrained as riding atoms with C—H = 0.95–0.96 Å. The amide and hydroxyl protons were located in difference Fourier maps and constrained with N—H, O—H = 0.90 Å. 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 of the intramolecular N—H···O and O—H···O hydrogen bonding (dashed lines) in (I).

Crystal data

C18H20ClNO4F000 = 736
Mr = 349.80Dx = 1.328 Mg m3
Monoclinic, P21/nMo Kα radiation λ = 0.7107 Å
Hall symbol: -P 2ynCell parameters from 25 reflections
a = 12.329 (3) Åθ = 12.7–16.7º
b = 12.839 (5) ŵ = 0.24 mm1
c = 11.062 (3) ÅT = 295 K
β = 92.18 (2)ºPrismatic, colourless
V = 1749.8 (9) Å30.35 × 0.35 × 0.15 mm
Z = 4

Data collection

Rigaku AFC-7R diffractometerRint = 0.034
Radiation source: Rigaku rotating anodeθmax = 25.0º
Monochromator: graphiteθmin = 2.5º
T = 295 Kh = −14→6
ω–2θ scansk = 0→15
Absorption correction: nonel = −13→13
3463 measured reflections3 standard reflections
3078 independent reflections every 150 reflections
1596 reflections with I > 2σ(I) intensity decay: 0.2%

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.056H-atom parameters constrained
wR(F2) = 0.165  w = 1/[σ2(Fo2) + (0.0802P)2] where P = (Fo2 + 2Fc2)/3
S = 0.99(Δ/σ)max < 0.001
3078 reflectionsΔρmax = 0.21 e Å3
217 parametersΔρmin = −0.31 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none

Special details

Experimental. The scan width was (1.68 + 0.30tanθ)° with an ω scan speed of 16° per minute (up to 4 scans to achieve I/σ(I) > 10). Stationary background counts were recorded at each end of the scan, and the scan time:background time ratio was 2:1.
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 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 > 2σ(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)

xyzUiso*/Ueq
Cl30.45169 (9)0.55050 (8)0.30062 (9)0.0775 (4)
O40.28934 (19)0.46680 (18)0.13154 (19)0.0576 (8)
O80.5970 (2)0.0875 (2)0.5455 (2)0.0730 (10)
O131.02796 (18)0.23926 (19)0.5658 (2)0.0617 (9)
O140.94460 (19)0.41834 (18)0.6082 (2)0.0596 (9)
N10.5696 (2)0.1267 (2)0.3474 (3)0.0582 (11)
C10.3920 (3)0.2566 (3)0.3989 (3)0.0520 (12)
C20.4348 (3)0.3564 (3)0.3927 (3)0.0531 (14)
C30.3990 (3)0.4245 (3)0.3042 (3)0.0488 (12)
C40.3205 (3)0.3961 (3)0.2174 (3)0.0449 (11)
C50.2765 (3)0.2977 (3)0.2247 (3)0.0506 (12)
C60.3118 (3)0.2284 (3)0.3136 (3)0.0544 (12)
C70.4368 (3)0.1806 (3)0.4917 (3)0.0640 (16)
C80.5425 (3)0.1284 (3)0.4612 (4)0.0555 (12)
C90.6665 (3)0.0772 (3)0.3040 (4)0.0674 (16)
C100.7448 (3)0.1555 (3)0.2523 (3)0.0669 (14)
C110.7947 (3)0.2290 (3)0.3448 (3)0.0541 (14)
C120.8890 (3)0.1991 (3)0.4103 (3)0.0527 (12)
C130.9362 (3)0.2626 (3)0.4968 (3)0.0488 (11)
C140.8904 (3)0.3599 (3)0.5209 (3)0.0506 (11)
C150.7965 (3)0.3898 (3)0.4579 (3)0.0576 (12)
C160.7501 (3)0.3244 (3)0.3708 (3)0.0613 (14)
C171.0790 (3)0.1422 (3)0.5422 (4)0.0773 (17)
C180.8999 (3)0.5175 (3)0.6355 (4)0.0728 (17)
H10.529200.153400.284700.0690*
H20.489400.377900.450400.0640*
H40.229200.443900.091300.0690*
H50.221000.277100.167800.0600*
H60.280900.160700.316400.0650*
H7A0.448300.217200.565800.0770*
H7B0.384000.127700.501700.0770*
H9A0.702200.041600.369400.0810*
H9B0.645800.028600.242600.0810*
H10A0.801600.118200.216000.0800*
H10B0.706600.195600.192400.0800*
H120.921000.133500.394500.0630*
H150.764000.455000.474300.0690*
H160.685800.345800.327900.0730*
H17A1.145500.137700.588200.0930*
H17B1.032600.086800.564300.0930*
H17C1.092900.137300.458600.0930*
H18A0.829400.508400.666000.0870*
H18B0.945200.551400.694600.0870*
H18C0.895000.558500.564100.0870*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl30.0899 (8)0.0688 (7)0.0723 (7)−0.0335 (6)−0.0161 (5)0.0010 (5)
O40.0595 (15)0.0560 (15)0.0560 (14)−0.0045 (12)−0.0141 (12)0.0018 (12)
O80.0645 (17)0.0801 (19)0.0720 (17)0.0059 (15)−0.0273 (14)0.0085 (15)
O130.0508 (15)0.0643 (17)0.0686 (16)0.0122 (13)−0.0165 (12)−0.0127 (13)
O140.0601 (16)0.0540 (16)0.0643 (15)0.0047 (13)−0.0015 (12)−0.0106 (12)
N10.0493 (19)0.067 (2)0.057 (2)0.0096 (16)−0.0136 (15)−0.0031 (16)
C10.050 (2)0.052 (2)0.054 (2)0.0073 (18)0.0011 (17)0.0026 (17)
C20.045 (2)0.064 (3)0.050 (2)−0.0033 (18)−0.0018 (16)−0.0048 (18)
C30.047 (2)0.049 (2)0.050 (2)−0.0101 (17)−0.0029 (16)−0.0042 (17)
C40.0438 (19)0.045 (2)0.0461 (19)0.0037 (17)0.0030 (15)−0.0058 (16)
C50.040 (2)0.050 (2)0.061 (2)−0.0008 (16)−0.0082 (17)−0.0053 (17)
C60.053 (2)0.045 (2)0.065 (2)0.0008 (17)0.0003 (18)−0.0048 (18)
C70.069 (3)0.063 (3)0.060 (2)0.012 (2)0.0017 (19)0.0085 (19)
C80.056 (2)0.047 (2)0.062 (2)−0.0032 (18)−0.017 (2)−0.0027 (19)
C90.056 (2)0.066 (3)0.079 (3)0.014 (2)−0.013 (2)−0.018 (2)
C100.051 (2)0.091 (3)0.058 (2)0.013 (2)−0.0077 (18)−0.010 (2)
C110.045 (2)0.068 (3)0.049 (2)0.0019 (19)−0.0020 (16)−0.0011 (18)
C120.045 (2)0.060 (2)0.053 (2)0.0025 (17)0.0000 (17)−0.0080 (18)
C130.0361 (19)0.056 (2)0.054 (2)0.0038 (17)−0.0033 (16)0.0037 (17)
C140.047 (2)0.058 (2)0.0474 (19)−0.0014 (18)0.0082 (16)0.0020 (18)
C150.055 (2)0.057 (2)0.061 (2)0.0103 (19)0.0056 (19)0.0072 (19)
C160.048 (2)0.072 (3)0.063 (2)0.010 (2)−0.0076 (18)0.008 (2)
C170.065 (3)0.078 (3)0.087 (3)0.025 (2)−0.022 (2)−0.017 (2)
C180.071 (3)0.065 (3)0.083 (3)0.004 (2)0.010 (2)−0.013 (2)

Geometric parameters (Å, °)

Cl3—C31.744 (4)C12—C131.370 (5)
O4—C41.359 (4)C13—C141.401 (5)
O8—C81.245 (5)C14—C151.383 (5)
O13—C131.374 (4)C15—C161.385 (5)
O13—C171.425 (5)C2—H20.9500
O14—C141.376 (4)C5—H50.9500
O14—C181.424 (5)C6—H60.9500
O4—H40.9000C7—H7A0.9500
N1—C91.451 (5)C7—H7B0.9500
N1—C81.315 (5)C9—H9A0.9500
N1—H10.9100C9—H9B0.9500
C1—C21.388 (5)C10—H10A0.9500
C1—C71.506 (5)C10—H10B0.9500
C1—C61.389 (5)C12—H120.9500
C2—C31.373 (5)C15—H150.9500
C3—C41.386 (5)C16—H160.9500
C4—C51.379 (5)C17—H17A0.9500
C5—C61.384 (5)C17—H17B0.9500
C7—C81.515 (5)C17—H17C0.9500
C9—C101.520 (5)C18—H18A0.9500
C10—C111.506 (5)C18—H18B0.9500
C11—C161.377 (5)C18—H18C0.9500
C11—C121.400 (5)
Cl3···O42.894 (3)C14···H18Cvii3.0300
Cl3···C12i3.646 (4)C15···H18A2.7800
Cl3···H12i2.9200C15···H9Bi2.9500
Cl3···H17Ci3.1100C15···H18C2.7300
Cl3···H2ii2.9700C17···H122.5000
O4···Cl32.894 (3)C17···H10Biv3.0600
O4···C17i3.411 (5)C18···H152.5300
O4···O8iii2.616 (4)H1···C12.5200
O8···C4iv3.295 (4)H1···C62.8800
O8···C5iv3.266 (5)H1···H10B2.5100
O8···O4iv2.616 (4)H1···O13iii2.7900
O8···C8v3.262 (5)H1···O14iii2.3700
O13···O142.569 (3)H2···H7A2.4900
O14···C6iv3.417 (4)H2···Cl3ii2.9700
O14···O132.569 (3)H4···H52.3100
O14···N1iv3.066 (4)H4···O8iii1.7400
O4···H17Ci2.8300H4···C8iii2.8200
O4···H18Aii2.7400H4···H9Aiii2.4700
O4···H6vi2.7100H5···H42.3100
O8···H9A2.4500H5···O8iii2.6500
O8···H4iv1.7400H6···H7B2.4100
O8···H7Bv2.8200H6···O4ix2.7100
O8···H5iv2.6500H7A···H22.4900
O13···H1iv2.7900H7B···H62.4100
O13···H10Biv2.7000H7B···O8v2.8200
O14···H18Cvii2.8100H9A···O82.4500
O14···H1iv2.3700H9A···C123.0900
N1···C23.431 (5)H9A···H4iv2.4700
N1···C63.443 (5)H9B···C15viii2.9500
N1···C163.379 (5)H10A···H122.4300
N1···O14iii3.066 (4)H10B···H12.5100
C2···N13.431 (5)H10B···H162.4600
C4···C18ii3.406 (5)H10B···O13iii2.7000
C4···O8iii3.295 (4)H10B···C17iii3.0600
C4···C13iii3.522 (5)H10B···H17Aiii2.5300
C5···C14iii3.375 (5)H12···C172.5000
C5···C13iii3.348 (5)H12···H10A2.4300
C5···O8iii3.266 (5)H12···H17B2.3600
C6···C14iii3.598 (5)H12···H17C2.2100
C6···N13.443 (5)H12···Cl3viii2.9200
C6···O14iii3.417 (4)H15···C182.5300
C8···C8v3.574 (6)H15···H18A2.3400
C8···O8v3.262 (5)H15···H18C2.2900
C12···Cl3viii3.646 (4)H16···H10B2.4600
C13···C4iv3.522 (5)H17A···H10Biv2.5300
C13···C5iv3.348 (5)H17B···C122.8100
C14···C18vii3.535 (6)H17B···H122.3600
C14···C6iv3.598 (5)H17C···C122.6700
C14···C5iv3.375 (5)H17C···H122.2100
C16···N13.379 (5)H17C···Cl3viii3.1100
C17···O4viii3.411 (5)H17C···O4viii2.8300
C18···C4ii3.406 (5)H18A···C152.7800
C18···C14vii3.535 (6)H18A···H152.3400
C1···H12.5200H18A···O4ii2.7400
C3···H18Aii2.9800H18A···C3ii2.9800
C4···H18Aii2.6000H18A···C4ii2.6000
C5···H18Aii3.0800H18A···C5ii3.0800
C6···H12.8800H18C···C152.7300
C8···H4iv2.8200H18C···H152.2900
C12···H17B2.8100H18C···O14vii2.8100
C12···H17C2.6700H18C···C14vii3.0300
C12···H9A3.0900
C13—O13—C17116.7 (3)C4—C5—H5119.00
C14—O14—C18117.1 (3)C6—C5—H5119.00
C4—O4—H4109.00C1—C6—H6120.00
C8—N1—C9124.5 (3)C5—C6—H6120.00
C9—N1—H1110.00C1—C7—H7A108.00
C8—N1—H1125.00C1—C7—H7B108.00
C2—C1—C7120.1 (3)C8—C7—H7A108.00
C6—C1—C7121.8 (3)C8—C7—H7B108.00
C2—C1—C6118.0 (3)H7A—C7—H7B109.00
C1—C2—C3120.7 (3)N1—C9—H9A109.00
Cl3—C3—C2119.8 (3)N1—C9—H9B109.00
Cl3—C3—C4118.6 (3)C10—C9—H9A109.00
C2—C3—C4121.6 (4)C10—C9—H9B109.00
O4—C4—C3118.7 (3)H9A—C9—H9B109.00
O4—C4—C5123.5 (3)C9—C10—H10A108.00
C3—C4—C5117.8 (3)C9—C10—H10B108.00
C4—C5—C6121.1 (3)C11—C10—H10A108.00
C1—C6—C5120.8 (4)C11—C10—H10B108.00
C1—C7—C8115.5 (3)H10A—C10—H10B109.00
O8—C8—N1124.1 (3)C11—C12—H12119.00
O8—C8—C7117.7 (4)C13—C12—H12119.00
N1—C8—C7118.2 (3)C14—C15—H15120.00
N1—C9—C10112.2 (3)C16—C15—H15120.00
C9—C10—C11114.1 (3)C11—C16—H16119.00
C10—C11—C16122.9 (3)C15—C16—H16119.00
C10—C11—C12119.3 (3)O13—C17—H17A109.00
C12—C11—C16117.8 (3)O13—C17—H17B109.00
C11—C12—C13121.4 (4)O13—C17—H17C110.00
O13—C13—C12125.3 (3)H17A—C17—H17B109.00
O13—C13—C14114.7 (3)H17A—C17—H17C109.00
C12—C13—C14120.0 (3)H17B—C17—H17C109.00
O14—C14—C15125.3 (3)O14—C18—H18A109.00
O14—C14—C13115.6 (3)O14—C18—H18B109.00
C13—C14—C15119.2 (3)O14—C18—H18C109.00
C14—C15—C16119.9 (4)H18A—C18—H18B109.00
C11—C16—C15121.8 (3)H18A—C18—H18C109.00
C1—C2—H2120.00H18B—C18—H18C110.00
C3—C2—H2120.00
C17—O13—C13—C121.8 (5)C3—C4—C5—C6−1.9 (5)
C17—O13—C13—C14−178.4 (3)C4—C5—C6—C10.7 (6)
C18—O14—C14—C13−179.7 (3)C1—C7—C8—O8161.4 (3)
C18—O14—C14—C150.1 (5)C1—C7—C8—N1−20.3 (5)
C9—N1—C8—O80.0 (6)N1—C9—C10—C1166.8 (4)
C9—N1—C8—C7−178.2 (3)C9—C10—C11—C1286.5 (4)
C8—N1—C9—C10−115.1 (4)C9—C10—C11—C16−91.8 (4)
C6—C1—C2—C3−0.4 (5)C10—C11—C12—C13−178.9 (3)
C7—C1—C2—C3176.3 (3)C16—C11—C12—C13−0.5 (5)
C2—C1—C6—C50.5 (5)C10—C11—C16—C15178.8 (3)
C7—C1—C6—C5−176.1 (3)C12—C11—C16—C150.5 (5)
C2—C1—C7—C8−78.9 (4)C11—C12—C13—O13179.5 (3)
C6—C1—C7—C897.7 (4)C11—C12—C13—C14−0.3 (5)
C1—C2—C3—Cl3178.4 (3)O13—C13—C14—O141.0 (4)
C1—C2—C3—C4−0.9 (6)O13—C13—C14—C15−178.7 (3)
Cl3—C3—C4—O41.3 (5)C12—C13—C14—O14−179.2 (3)
Cl3—C3—C4—C5−177.3 (3)C12—C13—C14—C151.1 (5)
C2—C3—C4—O4−179.4 (3)O14—C14—C15—C16179.2 (3)
C2—C3—C4—C52.0 (5)C13—C14—C15—C16−1.1 (5)
O4—C4—C5—C6179.5 (3)C14—C15—C16—C110.3 (5)

Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2; (ii) −x+1, −y+1, −z+1; (iii) x−1/2, −y+1/2, z−1/2; (iv) x+1/2, −y+1/2, z+1/2; (v) −x+1, −y, −z+1; (vi) −x+1/2, y+1/2, −z+1/2; (vii) −x+2, −y+1, −z+1; (viii) −x+3/2, y−1/2, −z+1/2; (ix) −x+1/2, y−1/2, −z+1/2.

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O14iii0.912.373.066 (4)134
O4—H4···O8iii0.901.742.616 (4)165

Symmetry codes: (iii) x−1/2, −y+1/2, z−1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: TK2268).

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