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Acta Cryst. (2009). E65, o297    [ doi:10.1107/S160053680804405X ]

(2S)-1,1-Dichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl)ethane

T. Cantillana and L. Eriksson

Abstract top

The title compound, C14H10Cl4, is easily crystallized while the other enantiomorph only forms an oil upon crystallization attempts. The title compound has a considerably higher density, [rho] [asymptotically equal to] 1.562 Mg m-3 compared to the racemic substance, [rho] [asymptotically equal to] 1.514 Mg m-3. This is supported by the fact there are two intermolecular halogen-halogen contacts in the title compound compared with only one the racemic compound. The dihedral angle between the two phenyl rings is 76.83 (5)°

Comment top

The title compound is commercially available as a racemate which has been structurally characterized earlier (Arora & Bates, 1976). When purifying and separating the two enantiomers of the racemate, one of the enantiomers, the title compound easily formed crystals while the other enantiomer only formed an oil upon crystallization attempts. A salient feature of the racemic compound o,p'-DDD (Mitotane) is its selective toxicity to the adrenal cortex. It has been used for 40 years for treatment of adrenocortical carcinoma (ACC) (Bergenstal et al., 1960) and Cushing's syndrome (Benecke et al., 1991). The efficacy and potency is however low, and o,p'-DDD treatment is frequently associated with severe side effects (Allolio & Fassnacht, 2006). The differences in toxicity of the two enantiomers of o,p'-DDD and the pharmacokinetics connected with these two compounds has recently been examined in Göttingen mini pigs and will be reported elsewhere (Cantillana et al., 2009).

The crystal structure of (I) shown in Fig. 1 show normal bond distances and angles. The dihedral angle between the two phenyl rings is 76.83 (5)°. Both phenyl rings are planar within 0.01 Å with the Cl3 deviating 0.103 (2) Å from the least square plane calculated from C3→C8 and the Cl4 deviating 0.048 (2) from the least square plane of C9→C14. All four chlorines are involved in the intermolecular Cl···Cl contacts between the different molecules building up a corrugated layer extending in the [010] and [101] directions. The title compound has a considerably higher density, ρ≈ 1.562 g/cm3 compared to the racemate, ρ≈ 1.514 g/cm3 (Arora & Bates, 1976). A tentative model for the higher density of the pure enantiomer is that it may be a result of the more numerous intermolecular short halogen-halogen contacts.

Related literature top

For related literature, regarding the structure of the racemic compound, see: Arora & Bates (1976). For related literature on the toxicological effects, see: Allolio & Fassnacht (2006), Benecke et al. (1991), Bergenstal et al. (1960).

For related literature, see: Cantillana et al. (2009).

Experimental top

The title compound was purified from a racemic mixture present in the commercially available product, 1,1-Dichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl)ethane (o,p'-DDD) using high performance liquid chromatography (HPLC), Shimadzu LC-9 A (Kyoto, Japan) equipped with an UV detector, UV100 from Spectra-Physics (Fremont, USA) and a permethylated γ-cyclodextrin column, Nucleodex gamma-PM (250 x 10 mm, 5µm, Macherey-Nagel GmbH & Co, Düren, Germany). The detection wavelength was 240 nm and the flow rate was 4 ml/min and injection volume of 200µl. The mobile phase was methanol:water (80:20) and 1% triethylamine:acetic acid (1:2 v/v). Thin plate-like crystals suitable for X-ray analysis were obtained upon recrystallization from methanol.

Refinement top

The hydrogen atoms were geometrically positioned at C—H distances of 0.95 and 1.00 Å for the aromatic and methine hydrogen's. Both types of hydrogen's were given U(iso) = 1.2Ueq(C). The completeness of the data increases to 0.994 if one cuts the reflection data at 2θ = 50°.

Computing details top

Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffraction, 2008); data reduction: CrysAlis RED (Oxford Diffraction, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Bergerhoff, 1996); software used to prepare material for publication: PLATON (Spek, 2003) and SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The title compound (I) with displacement ellipsoids at 50% probability with the unique atoms labeled.
(2S)-1,1-Dichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl)ethane top
Crystal data top
C14H10Cl4F(000) = 324
Mr = 320.02Dx = 1.562 Mg m−3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 11963 reflections
a = 6.1353 (1) Åθ = 3.8–32.1°
b = 12.0715 (2) ŵ = 0.85 mm−1
c = 9.4525 (2) ÅT = 100 K
β = 103.5490 (18)°Plate, colourless
V = 680.59 (2) Å30.34 × 0.24 × 0.04 mm
Z = 2
Data collection top
Oxford Diffraction Xcalibur-3 κ-
diffractometer with Sapphire-III CCD		4258 independent reflections
Radiation source: Enhance (Mo) X-ray Source3935 reflections with I > 2σ(I)
graphiteRint = 0.032
Detector resolution: 16.54 pixels mm-1θmax = 32.2°, θmin = 3.8°
ω scans at different φh = −9→9
Absorption correction: gaussian
(CrysAlis RED; Oxford Diffraction, 2008)		k = −17→15
Tmin = 0.814, Tmax = 0.968l = −13→14
18569 measured reflections
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.026 w = 1/[σ2(Fo2) + (0.0358P)2]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.060(Δ/σ)max = 0.001
S = 1.01Δρmax = 0.40 e Å−3
4258 reflectionsΔρmin = −0.31 e Å−3
164 parametersExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.009 (2)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983), 1755 Friedel pairs
Secondary atom site location: difference Fourier mapFlack parameter: 0.00 (4)
Crystal data top
C14H10Cl4V = 680.59 (2) Å3
Mr = 320.02Z = 2
Monoclinic, P21Mo Kα radiation
a = 6.1353 (1) ŵ = 0.85 mm−1
b = 12.0715 (2) ÅT = 100 K
c = 9.4525 (2) Å0.34 × 0.24 × 0.04 mm
β = 103.5490 (18)°
Data collection top
Oxford Diffraction Xcalibur-3 κ-
diffractometer with Sapphire-III CCD		4258 independent reflections
Absorption correction: gaussian
(CrysAlis RED; Oxford Diffraction, 2008)		3935 reflections with I > 2σ(I)
Tmin = 0.814, Tmax = 0.968Rint = 0.032
18569 measured reflectionsθmax = 32.2°
Refinement top
R[F2 > 2σ(F2)] = 0.026H-atom parameters constrained
wR(F2) = 0.060Δρmax = 0.40 e Å−3
S = 1.01Δρmin = −0.31 e Å−3
4258 reflectionsAbsolute structure: Flack (1983), 1755 Friedel pairs
164 parametersFlack parameter: 0.00 (4)
1 restraint
Special details top

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
xyzUiso*/Ueq
C10.5723 (2)0.58327 (13)0.35281 (15)0.0153 (3)
H10.41790.55130.33600.018*
C20.5682 (2)0.70231 (12)0.40708 (16)0.0136 (3)
H20.72330.73300.42190.016*
Cl10.75951 (6)0.50047 (3)0.48348 (4)0.02031 (8)
Cl20.66068 (6)0.58092 (3)0.18581 (4)0.02172 (9)
C30.4118 (2)0.77539 (12)0.29597 (15)0.0143 (3)
C40.4896 (3)0.87540 (13)0.25332 (16)0.0178 (3)
H40.64340.89430.28710.021*
C50.3459 (3)0.94815 (14)0.16209 (16)0.0196 (3)
H50.40061.01620.13350.024*
C60.1222 (3)0.92006 (14)0.11361 (15)0.0174 (3)
C70.0412 (3)0.81928 (14)0.15077 (17)0.0197 (3)
H7−0.11160.79960.11410.024*
C80.1859 (2)0.74824 (14)0.24185 (17)0.0185 (3)
H80.13100.67960.26830.022*
Cl3−0.06289 (6)1.01373 (3)0.00690 (4)0.02230 (9)
C90.5012 (2)0.70772 (12)0.55256 (16)0.0149 (3)
C100.3199 (3)0.64714 (13)0.57858 (16)0.0177 (3)
H100.24240.59740.50620.021*
C110.2503 (3)0.65801 (14)0.70765 (17)0.0192 (3)
H110.12630.61620.72230.023*
C120.3609 (3)0.72933 (15)0.81459 (17)0.0212 (3)
H120.31290.73660.90260.025*
C130.5417 (3)0.79019 (14)0.79373 (17)0.0207 (3)
H130.61920.83890.86740.025*
C140.6088 (2)0.77922 (13)0.66334 (16)0.0157 (3)
Cl40.83309 (6)0.86142 (3)0.64058 (4)0.02012 (8)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0144 (6)0.0158 (7)0.0172 (6)0.0000 (5)0.0071 (5)−0.0006 (6)
C20.0121 (6)0.0131 (7)0.0159 (6)−0.0025 (5)0.0041 (5)−0.0019 (5)
Cl10.01984 (16)0.01761 (17)0.02400 (17)0.00417 (14)0.00622 (12)0.00057 (14)
Cl20.02671 (18)0.02192 (19)0.02051 (16)−0.00424 (15)0.01356 (14)−0.00507 (14)
C30.0158 (6)0.0140 (7)0.0139 (6)−0.0016 (5)0.0054 (5)−0.0012 (5)
C40.0171 (6)0.0189 (8)0.0175 (6)−0.0054 (6)0.0042 (5)−0.0007 (6)
C50.0261 (8)0.0167 (7)0.0162 (7)−0.0061 (6)0.0054 (6)0.0018 (5)
C60.0210 (7)0.0189 (7)0.0129 (6)0.0025 (6)0.0052 (5)0.0020 (5)
C70.0173 (7)0.0212 (8)0.0202 (7)−0.0024 (6)0.0039 (6)0.0019 (6)
C80.0171 (7)0.0174 (7)0.0206 (7)−0.0043 (6)0.0037 (5)0.0021 (6)
Cl30.02784 (18)0.02156 (19)0.01717 (15)0.00582 (15)0.00459 (13)0.00309 (14)
C90.0156 (6)0.0138 (7)0.0154 (6)0.0041 (5)0.0034 (5)0.0005 (5)
C100.0205 (7)0.0166 (7)0.0172 (6)0.0015 (6)0.0070 (5)0.0021 (6)
C110.0186 (7)0.0203 (8)0.0205 (7)0.0034 (6)0.0081 (6)0.0048 (6)
C120.0263 (8)0.0224 (8)0.0163 (7)0.0089 (7)0.0077 (6)0.0029 (6)
C130.0258 (8)0.0189 (8)0.0158 (7)0.0070 (6)0.0020 (6)−0.0012 (6)
C140.0146 (6)0.0126 (7)0.0185 (6)0.0029 (5)0.0013 (5)−0.0002 (5)
Cl40.01702 (16)0.01679 (17)0.02510 (18)−0.00235 (13)0.00201 (13)−0.00440 (14)
Geometric parameters (Å, °) top
C1—C21.528 (2)C7—C81.381 (2)
C1—Cl11.7831 (15)C7—H70.9500
C1—Cl21.7855 (14)C8—H80.9500
C1—H11.0000C9—C141.398 (2)
C2—C91.526 (2)C9—C101.400 (2)
C2—C31.526 (2)C10—C111.390 (2)
C2—H21.0000C10—H100.9500
C3—C41.392 (2)C11—C121.379 (2)
C3—C81.399 (2)C11—H110.9500
C4—C51.391 (2)C12—C131.382 (2)
C4—H40.9500C12—H120.9500
C5—C61.383 (2)C13—C141.394 (2)
C5—H50.9500C13—H130.9500
C6—C71.390 (2)C14—Cl41.7503 (16)
C6—Cl31.7462 (16)
Cl1···Cl4i3.4370 (5)Cl2···Cl3ii3.4888 (5)
C2—C1—Cl1110.68 (10)C8—C7—C6119.01 (14)
C2—C1—Cl2110.12 (10)C8—C7—H7120.5
Cl1—C1—Cl2108.88 (8)C6—C7—H7120.5
C2—C1—H1109.0C7—C8—C3121.31 (14)
Cl1—C1—H1109.0C7—C8—H8119.3
Cl2—C1—H1109.0C3—C8—H8119.3
C9—C2—C3109.67 (11)C14—C9—C10116.49 (13)
C9—C2—C1111.82 (12)C14—C9—C2121.46 (13)
C3—C2—C1111.69 (12)C10—C9—C2121.92 (13)
C9—C2—H2107.8C11—C10—C9121.65 (15)
C3—C2—H2107.8C11—C10—H10119.2
C1—C2—H2107.8C9—C10—H10119.2
C4—C3—C8118.35 (14)C12—C11—C10120.19 (15)
C4—C3—C2119.83 (13)C12—C11—H11119.9
C8—C3—C2121.69 (13)C10—C11—H11119.9
C5—C4—C3121.07 (14)C11—C12—C13120.04 (14)
C5—C4—H4119.5C11—C12—H12120.0
C3—C4—H4119.5C13—C12—H12120.0
C6—C5—C4119.09 (15)C12—C13—C14119.25 (15)
C6—C5—H5120.5C12—C13—H13120.4
C4—C5—H5120.5C14—C13—H13120.4
C5—C6—C7121.11 (15)C13—C14—C9122.37 (15)
C5—C6—Cl3119.54 (13)C13—C14—Cl4117.29 (12)
C7—C6—Cl3119.33 (12)C9—C14—Cl4120.33 (12)
Cl1—C1—C2—C9−57.58 (13)C2—C3—C8—C7174.53 (14)
Cl2—C1—C2—C9−178.02 (9)C3—C2—C9—C14−96.67 (15)
Cl1—C1—C2—C3179.08 (9)C1—C2—C9—C14138.85 (14)
Cl2—C1—C2—C358.64 (13)C3—C2—C9—C1078.99 (17)
C9—C2—C3—C4107.05 (15)C1—C2—C9—C10−45.48 (18)
C1—C2—C3—C4−128.40 (14)C14—C9—C10—C110.2 (2)
C9—C2—C3—C8−68.77 (17)C2—C9—C10—C11−175.63 (14)
C1—C2—C3—C855.78 (18)C9—C10—C11—C12−0.3 (2)
C8—C3—C4—C51.6 (2)C10—C11—C12—C13−0.1 (2)
C2—C3—C4—C5−174.36 (14)C11—C12—C13—C140.6 (2)
C3—C4—C5—C60.1 (2)C12—C13—C14—C9−0.7 (2)
C4—C5—C6—C7−2.1 (2)C12—C13—C14—Cl4178.08 (12)
C4—C5—C6—Cl3176.66 (12)C10—C9—C14—C130.3 (2)
C5—C6—C7—C82.3 (2)C2—C9—C14—C13176.15 (14)
Cl3—C6—C7—C8−176.42 (12)C10—C9—C14—Cl4−178.44 (11)
C6—C7—C8—C3−0.6 (2)C2—C9—C14—Cl4−2.55 (19)
C4—C3—C8—C7−1.3 (2)
Symmetry codes: (i) −x+2, y−1/2, −z+1; (ii) −x+1, y−1/2, −z.
Table 1
Selected geometric parameters (Å) top
Cl1···Cl4i3.4370 (5)Cl2···Cl3ii3.4888 (5)
Symmetry codes: (i) −x+2, y−1/2, −z+1; (ii) −x+1, y−1/2, −z.
Acknowledgements top

This work was supported by a grant from the Swedish Research Council and by the Faculty of Natural Sciences at Stockholm University

references
References top

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