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Acta Crystallogr Sect E Struct Rep Online. 2008 October 1; 64(Pt 10): o2030.
Published online 2008 September 27. doi:  10.1107/S1600536808030699
PMCID: PMC2959265

1-(5-Chloro-2,4-dihydroxy­phen­yl)-2-(4-ethoxy­phen­yl)ethanone

Abstract

The structure of the title compound, C16H15ClO4, contains aryl rings which are inclined by 75.6 (1)° to each other. It displays intra­molecular O—H(...)O hydrogen bonding between the 2-hydr­oxy and carbonyl groups, forming a six-membered ring. Furthermore, the 4-hydr­oxy group, acting as a hydrogen-bond donor, is bound to the O atom of the 2-hydr­oxy group of another mol­ecule.

Related literature

For related literature, see: Anderson & Garner (1997 [triangle]); Fokialakis et al. (2004 [triangle]); Papoutsi et al. (2007 [triangle]); Anthony (2002 [triangle]); Barnes (1998 [triangle]); Barnes & Peterson (1995 [triangle]); Dixon & Ferreira (2002 [triangle]); Greenwood et al. (2000 [triangle]); Setchell (1998 [triangle]); Whalley et al. (2000 [triangle]). For a related structure, see: Arumugan et al. (2007 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-o2030-scheme1.jpg

Experimental

Crystal data

  • C16H15ClO4
  • M r = 306.73
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o2030-efi1.jpg
  • a = 19.255 (6) Å
  • b = 4.6454 (15) Å
  • c = 31.109 (11) Å
  • β = 90.519 (7)°
  • V = 2782.5 (16) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 0.29 mm−1
  • T = 125 (2) K
  • 0.11 × 0.03 × 0.03 mm

Data collection

  • Bruker SMART diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2001 [triangle]) T min = 0.983, T max = 0.997
  • 8448 measured reflections
  • 2515 independent reflections
  • 1401 reflections with I > 2σ(I)
  • R int = 0.091

Refinement

  • R[F 2 > 2σ(F 2)] = 0.049
  • wR(F 2) = 0.101
  • S = 0.89
  • 2515 reflections
  • 199 parameters
  • 2 restraints
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.28 e Å−3
  • Δρmin = −0.27 e Å−3

Data collection: SMART (Bruker, 2001 [triangle]); cell refinement: SMART; data reduction: SAINT (Bruker, 2001 [triangle]); program(s) used to solve structure: SHELXTL (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808030699/wn2279sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808030699/wn2279Isup2.hkl

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

supplementary crystallographic information

Comment

Phytoestrogens, in particular the soy isoflavones such as daidzein and genistein, have positive impact on human health (Setchell, 1998; Barnes, 1998 and Dixon & Ferreira, 2002). High consumption of soy products has been associated with a low incidence of hormone-dependent cancers (Barnes & Peterson, 1995), the symptom alleviation of menopause (Greenwood et al., 2000) and protection against osteoporosis (Anderson & Garner, 1997) as well as cardiovascular disease (Anthony, 2002). Consequently, there is growing interest in using phytoestrogens and synthetic derivatives for the chemoprevention and therapy of these diseases.

One of the synthetic routes to daidzein and its derivatives is via the Freidel-Crafts reaction of resorcinol and phenylacetic acid catalysed by boron trifluoride etherate (Whalley, et al., 2000), giving the deoxybenzoin intermediate. In the preparation of 5-chlorodaidzein, 1-(5-chloro-2,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)-ethanone (2) was obtained (yield 77%) from the coupling of 5-cholororesorcinol with 4-hydroxyphenylacetic acid in boron trifluoride etherate. Surprisingly, the title compound, 1-(5-chloro-2,4-dihydroxyphenyl)-2-(4-ethoxyphenyl)-ethanone (1), was also isolated in small amount (5% yield). Boron trifluoride proves to be such a strong Lewis acid, it not only catalyses the Freidel-Crafts reaction, but also activates the diethyl ether and makes it an electrophile. From the position of ethylation, it can be concluded that (1) is formed from the attack of (2) via 4-hydroxyphenyl to the α-position of the actived diethyl ether, because the 4-OH of the benzyl ring is more nucleophilic than the 2-OH and the 4-OH in the other phenyl ring which bears the electron-withdrawing carbonyl group. (1) has been previously synthesized as the major product from 5-chlororesorcinol and 4-ethoxyphenylacetic acid (Fokialakis et al. 2004). The deoxybenzoin shows some estrogenic activity like daidzein (Fokialakis et al., 2004; Papoutsi et al., 2007).

The molecular structure of (1) is conformationally similar to that of deoxyanisoin, MeOC6H4C(O)CH2C6H4OMe. (Arumugan et al. 2007) with statistically invariant C═O and C—C bond lengths and very similar backbone torsion angles, though C4—O4 in 1 appears to be marginally shorter at 1.347 (3) Å than in deoxyanisoin at 1.378 (1) Å; this may be a consequence of the neighbouring chloro substituent in (1).

Experimental

Boron trifluoride diethyl etherate (7.7 ml, 60.7 mmol) was added to a mixture of resorcinol (4.4 g, 30.4 mmol) and 3-chloro-4-hydroxyphenylacetic acid (4.63 g, 30.4 mmol) under a nitrogen atmosphere. The mixture was heated to reflux for 5 h, cooled to room temperature, and saturated aqueous sodium acetate (50 ml) and aqueous sodium hydrogen carbonate (40 ml) added sequentially. The mixture was extracted with diethyl ether (3 × 50 ml), dried MgSO4 and the solvent removed at reduced pressure.Column chromatography on silica, with hexane/ethyl acetate (1:1) as eluant, gave the title compound (1) (0.47 g, 5%). 1H NMR and 13C NMR (CDCl3) of (1) as well as MS were in agreement with that in the literature (Fokialakis et al., 2004).

Refinement

All carbon-bound H-atoms were included in calculated positions (C—H distances are 0.98 Å for methyl H atoms, 0.99 Å for methylene H and 0.95 Å for aryl H atoms) and were refined as riding atoms with Uiso(H) = xUeq(parent atom), where x = 1.2 for methylene and aryl H atoms, 1.5 for methyl H atoms. The OH hydrogen atoms were located in a difference map and refined isotropically, subject to a distance restraint, 0.98 (1) Å.

Figures

Fig. 1.
The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level. Carbon-bound H atoms have been omitted; H atoms bonded to oxygen are represented as spheres of arbitrary radius.
Fig. 2.
A packing diagram, with hydrogen bonding interactions indicated as dashed lines. Hydrogen atoms not involved in hydrogen bonding have been omitted.

Crystal data

C16H15ClO4F(000) = 1280
Mr = 306.73Dx = 1.464 Mg m3
Monoclinic, I2/aMo Kα radiation, λ = 0.71073 Å
a = 19.255 (6) ÅCell parameters from 306 reflections
b = 4.6454 (15) Åθ = 12–28°
c = 31.109 (11) ŵ = 0.29 mm1
β = 90.519 (7)°T = 125 K
V = 2782.5 (16) Å3Prism, colourless
Z = 80.11 × 0.03 × 0.03 mm

Data collection

Bruker SMART diffractometer2515 independent reflections
Radiation source: fine-focus sealed tube1401 reflections with I > 2σ(I)
graphiteRint = 0.091
Detector resolution: 0.83 pixels mm-1θmax = 25.4°, θmin = 2.1°
[var phi] and ω scansh = −22→23
Absorption correction: multi-scan (SADABS; Bruker, 2001)k = −5→5
Tmin = 0.983, Tmax = 0.997l = −37→31
8448 measured reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.049Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.101H atoms treated by a mixture of independent and constrained refinement
S = 0.89w = 1/[σ2(Fo2) + (0.0438P)2] where P = (Fo2 + 2Fc2)/3
2515 reflections(Δ/σ)max = 0.033
199 parametersΔρmax = 0.28 e Å3
2 restraintsΔρmin = −0.27 e Å3

Special details

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)

xyzUiso*/Ueq
C10.33978 (15)0.7593 (6)0.18759 (10)0.0179 (7)
C20.39148 (16)0.8676 (6)0.21571 (10)0.0178 (8)
O20.37615 (11)1.0672 (4)0.24646 (7)0.0217 (5)
H2O0.3277 (6)1.130 (8)0.2439 (13)0.076 (14)*
C30.45909 (15)0.7723 (6)0.21336 (10)0.0189 (7)
H3A0.49310.84740.23260.023*
C40.47810 (16)0.5683 (6)0.18323 (10)0.0193 (8)
O40.54308 (11)0.4628 (5)0.18053 (7)0.0258 (6)
H4O0.5655 (16)0.516 (8)0.2078 (6)0.064 (13)*
C50.42808 (16)0.4638 (6)0.15414 (10)0.0195 (8)
Cl50.45154 (4)0.21806 (16)0.11487 (3)0.0265 (3)
C60.36084 (16)0.5567 (6)0.15684 (10)0.0192 (8)
H6A0.32730.48170.13730.023*
C70.26827 (16)0.8586 (6)0.19047 (10)0.0193 (8)
O70.25248 (11)1.0457 (5)0.21737 (7)0.0295 (6)
C80.21213 (15)0.7476 (6)0.16079 (10)0.0234 (8)
H8A0.22670.56040.14860.028*
H8B0.16920.71560.17740.028*
C90.19729 (16)0.9550 (6)0.12476 (10)0.0187 (8)
C100.24738 (17)1.0299 (7)0.09503 (11)0.0258 (8)
H10A0.29250.94860.09740.031*
C110.23309 (16)1.2204 (7)0.06193 (10)0.0270 (8)
H11A0.26811.26870.04190.032*
C120.16775 (17)1.3401 (7)0.05814 (11)0.0239 (8)
C130.11677 (16)1.2740 (6)0.08744 (10)0.0234 (8)
H13A0.07191.35820.08510.028*
C140.13229 (16)1.0809 (6)0.12065 (10)0.0222 (8)
H14A0.09741.03490.14090.027*
O120.15829 (10)1.5204 (5)0.02307 (7)0.0293 (6)
C150.09030 (16)1.6385 (7)0.01654 (11)0.0271 (9)
H15A0.07731.76140.04120.033*
H15B0.05561.48240.01360.033*
C160.09290 (17)1.8138 (7)−0.02397 (11)0.0336 (9)
H16A0.04721.8999−0.02960.050*
H16B0.10551.6894−0.04810.050*
H16C0.12761.9667−0.02070.050*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0173 (17)0.0189 (17)0.0175 (18)−0.0018 (14)−0.0035 (14)0.0016 (14)
C20.0209 (19)0.0137 (16)0.019 (2)−0.0004 (14)−0.0014 (15)0.0023 (13)
O20.0231 (13)0.0224 (12)0.0195 (13)0.0028 (10)−0.0057 (11)−0.0029 (10)
C30.0188 (17)0.0197 (17)0.0181 (18)−0.0015 (15)−0.0058 (14)0.0000 (15)
C40.0155 (17)0.0210 (18)0.021 (2)0.0020 (15)−0.0025 (15)0.0071 (15)
O40.0217 (13)0.0300 (14)0.0257 (15)0.0023 (11)−0.0048 (11)−0.0025 (11)
C50.0269 (19)0.0146 (17)0.0170 (19)−0.0009 (15)−0.0009 (16)0.0008 (14)
Cl50.0277 (5)0.0265 (5)0.0250 (5)0.0027 (4)−0.0029 (4)−0.0061 (4)
C60.0208 (18)0.0156 (17)0.021 (2)0.0002 (14)−0.0031 (15)−0.0006 (14)
C70.0247 (19)0.0157 (17)0.017 (2)−0.0003 (14)−0.0004 (16)0.0028 (14)
O70.0270 (13)0.0342 (14)0.0273 (15)0.0057 (11)−0.0066 (11)−0.0070 (11)
C80.0191 (17)0.0207 (18)0.030 (2)−0.0013 (15)−0.0065 (15)0.0011 (16)
C90.0183 (18)0.0181 (18)0.020 (2)−0.0014 (15)−0.0037 (16)−0.0024 (14)
C100.0191 (18)0.031 (2)0.028 (2)0.0033 (16)−0.0058 (17)−0.0016 (17)
C110.0193 (18)0.038 (2)0.024 (2)−0.0013 (17)0.0011 (15)−0.0004 (17)
C120.029 (2)0.0213 (18)0.021 (2)−0.0015 (15)−0.0079 (17)−0.0006 (15)
C130.0203 (17)0.0201 (18)0.030 (2)0.0024 (15)−0.0057 (16)−0.0024 (16)
C140.0222 (19)0.0230 (18)0.021 (2)−0.0043 (15)0.0019 (16)−0.0006 (15)
O120.0236 (13)0.0358 (14)0.0285 (15)0.0003 (11)−0.0052 (11)0.0087 (11)
C150.0272 (19)0.0232 (18)0.031 (2)0.0013 (15)−0.0077 (17)0.0063 (15)
C160.035 (2)0.035 (2)0.031 (2)0.0023 (18)−0.0047 (18)0.0049 (17)

Geometric parameters (Å, °)

C1—C61.404 (4)C9—C141.386 (4)
C1—C21.412 (4)C9—C101.387 (4)
C1—C71.456 (4)C10—C111.384 (4)
C2—O21.366 (4)C10—H10A0.9500
C2—C31.378 (4)C11—C121.380 (4)
O2—H2O0.9799 (11)C11—H11A0.9500
C3—C41.385 (4)C12—C131.380 (5)
C3—H3A0.9500C12—O121.386 (4)
C4—O41.347 (3)C13—C141.398 (4)
C4—C51.402 (4)C13—H13A0.9500
O4—H4O0.9800 (11)C14—H14A0.9500
C5—C61.368 (4)O12—C151.432 (4)
C5—Cl51.735 (3)C15—C161.502 (4)
C6—H6A0.9500C15—H15A0.9900
C7—O71.246 (4)C15—H15B0.9900
C7—C81.506 (4)C16—H16A0.9800
C8—C91.504 (4)C16—H16B0.9800
C8—H8A0.9900C16—H16C0.9800
C8—H8B0.9900
C6—C1—C2117.0 (3)C14—C9—C8120.3 (3)
C6—C1—C7122.2 (3)C10—C9—C8122.0 (3)
C2—C1—C7120.7 (3)C11—C10—C9121.5 (3)
O2—C2—C3117.7 (3)C11—C10—H10A119.3
O2—C2—C1121.3 (3)C9—C10—H10A119.3
C3—C2—C1120.9 (3)C12—C11—C10119.8 (3)
C2—O2—H2O111 (2)C12—C11—H11A120.1
C2—C3—C4120.8 (3)C10—C11—H11A120.1
C2—C3—H3A119.6C11—C12—C13120.5 (3)
C4—C3—H3A119.6C11—C12—O12115.1 (3)
O4—C4—C3122.8 (3)C13—C12—O12124.4 (3)
O4—C4—C5117.8 (3)C12—C13—C14118.8 (3)
C3—C4—C5119.3 (3)C12—C13—H13A120.6
C4—O4—H4O105 (2)C14—C13—H13A120.6
C6—C5—C4119.7 (3)C9—C14—C13121.7 (3)
C6—C5—Cl5120.2 (2)C9—C14—H14A119.1
C4—C5—Cl5120.0 (2)C13—C14—H14A119.1
C5—C6—C1122.2 (3)C12—O12—C15117.2 (3)
C5—C6—H6A118.9O12—C15—C16106.8 (3)
C1—C6—H6A118.9O12—C15—H15A110.4
O7—C7—C1119.9 (3)C16—C15—H15A110.4
O7—C7—C8118.2 (3)O12—C15—H15B110.4
C1—C7—C8121.9 (3)C16—C15—H15B110.4
C9—C8—C7111.6 (2)H15A—C15—H15B108.6
C9—C8—H8A109.3C15—C16—H16A109.5
C7—C8—H8A109.3C15—C16—H16B109.5
C9—C8—H8B109.3H16A—C16—H16B109.5
C7—C8—H8B109.3C15—C16—H16C109.5
H8A—C8—H8B108.0H16A—C16—H16C109.5
C14—C9—C10117.7 (3)H16B—C16—H16C109.5
C6—C1—C2—O2179.5 (3)C2—C1—C7—C8179.8 (3)
C7—C1—C2—O20.3 (4)O7—C7—C8—C978.3 (4)
C6—C1—C2—C3−1.4 (4)C1—C7—C8—C9−100.0 (3)
C7—C1—C2—C3179.4 (3)C7—C8—C9—C14−117.3 (3)
O2—C2—C3—C4179.4 (3)C7—C8—C9—C1061.9 (4)
C1—C2—C3—C40.2 (5)C14—C9—C10—C11−0.9 (5)
C2—C3—C4—O4−178.1 (3)C8—C9—C10—C11179.8 (3)
C2—C3—C4—C51.6 (5)C9—C10—C11—C120.1 (5)
O4—C4—C5—C6177.4 (3)C10—C11—C12—C130.8 (5)
C3—C4—C5—C6−2.3 (5)C10—C11—C12—O12−177.9 (3)
O4—C4—C5—Cl5−2.6 (4)C11—C12—C13—C14−0.8 (5)
C3—C4—C5—Cl5177.6 (2)O12—C12—C13—C14177.8 (3)
C4—C5—C6—C11.1 (5)C10—C9—C14—C130.9 (5)
Cl5—C5—C6—C1−178.8 (2)C8—C9—C14—C13−179.8 (3)
C2—C1—C6—C50.7 (5)C12—C13—C14—C9−0.1 (5)
C7—C1—C6—C5179.9 (3)C11—C12—O12—C15176.9 (3)
C6—C1—C7—O7−177.6 (3)C13—C12—O12—C15−1.7 (4)
C2—C1—C7—O71.5 (4)C12—O12—C15—C16−177.7 (3)
C6—C1—C7—C80.6 (4)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O2—H2O···O70.98 (1)1.71 (3)2.542 (3)141 (3)
O4—H4O···O2i0.98 (1)1.82 (1)2.784 (3)167 (3)

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: WN2279).

References

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Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography