2-(2,4-Di­chloro­phenyl­hydroxy­methyl)-1-tetralone

The reaction between 2,4-di­chloro­benz­aldehyde and 1-tetralone led to the isolation of two compounds. The expected product was 2-(2,4-di­chloro­phenyl­methyl­ene)-1-tetralone, (I). In addition, the title compound, C₁₇H₁₄Cl₂O₂, (II), was obtained. The mol­ecules of (II) are paired by hydrogen bonds around inversion centres.

Key indicators

• Single-crystal X-ray study
• T = 123 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.026
• wR factor = 0.075
• Data-to-parameter ratio = 18.5

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

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S1. Comment

A previous study from these laboratories revealed that the relative positions of the two aryl rings in a series of 2-arylidenebenzocycloalkanones influenced cytotoxicity towards various tumour cell lines (Dimmock et al., 1999). The different locations of the aryl rings resulted from altering the size of the cycloaliphatic ring. In these compounds, a three-carbon spacer consisting of an α,β-unsaturated keto group separated the two aryl rings. In the present study, an alternative three-carbon spacer was inserted between two aryl rings designated A and B (the aromatic ring in the tetralone moiety is A and the aromatic ring furthest from the tetralone moiety is B); such considerations led to the decision to prepare compound (I) and the accidental preparation of compound (II). The structure of (I) has been reported in the previous paper (Oloo et al., 2002). The present paper reports the structure of the title compound, (II).

The cyclohexenone (C1—C2—C3—C4—C5—C10) ring in (II) adopts the half-chair conformation, while the side chain at C2 is in the pseudo-equatorial position. The torsion angle C2—C11—C12—C17 is 100.49 (12)°, indicating that aryl ring B is twisted almost perpendicular to the plane of the tetralone moiety. This effect may be due to the Cl1···H11, O1···H11 and O2···H17 non-bonded repulsions, since these interatomic distances are 2.73, 2.48 and 2.47 Å, respectively.

Hydrogen bonds are tabulated in Table 1. The molecules are paired into dimers by one classical hydrogen bond per molecule from the O—H group of one molecule to the carbonyl O atom of a second molecule. Two intramolecular non-classical hydrogen bonds (C11—H11···Cl1 and C17—H17···O2) have reasonable distances but the bond angles at the H atoms are near 100°. The two meta-H atoms on the dichlorophenyl ring form non-classical hydrogen bonds to the O1 atoms of other molecules, giving a three-dimensional lattice of hydrogen bonds.

S2. Experimental

An ice-cold solution of sodium hydroxide (0.005 mol) in water (0.25 ml) and methanol (50 ml) was added to an ice-cold solution of 2,4-dichlorobenzaldehyde (0.01 mol) and 1-tetralone (0.01 mol) in methanol (75 ml). After stirring at room temperature for 2 d, the mixture was refrigerated (268 K) for 1 d and the precipitate collected and dried. Column chromatography using keiselgel 60 and an eluting solvent of toluene afforded (I) (m.p. 381–383 K) in 56% yield while an eluting solvent of 1% methanol in toluene led to (II) (m.p. 444–446 K) in 13% yield. Elemental analysis, calculated for C₁₇H₁₄Cl₂O₂: C 63.57, H 4.39%; found: C 63.38, H 4.45%. The cytotoxicity of (II) was determined using murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. The IC₅₀ figures of (II) in these four assays were 15.6±0.95, >500, ≥500 and ≥500 µM, respectively. Thus, apart from a marginally inferior potency towards P388 cells, compound (I) was significantly more cytotoxic than (II).

S3. Refinement

All H atoms were placed in calculated positions on the corresponding C or O atoms (C—H = 1.00 Å for methyne H atoms, 0.99 Å for methylene H atoms and 0.95 Å for aromatic H atoms, and O—H = 0.84 Å). For the OH group, the SHELXL97 command (Sheldrick, 1997) HFIX 147 was used. This utility calculates a difference electron density around the circle which represents the locus of possible H-atom positions for a fixed O—H distance and C—O—H angle. The U_iso value of each H atom was assigned as equal to 1.2 times the U_eq value of the attached atom.

Computing details

Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1992); cell refinement: CAD-4 EXPRESS; data reduction: Xtal3.7 (Hall et al., 2000); program(s) used to solve structure: Xtal3.7; program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: Xtal3.7; software used to prepare material for publication: SHELXL97.

Figures

Fig. 1. A general view of the title compound with non-H-atom displacement ellipsoids drawn at the 50% probability level.

2-(2,4-dichlorophenylhydroxymethyl)-1-tetralone

Crystal data

C17H14Cl2O2	F(000) = 1328
Mr = 321.18	Dx = 1.459 Mg m^−3
Monoclinic, C2/c	Melting point: 171° C-173° C K
Hall symbol: -C 2yc	Mo Kα radiation, λ = 0.71073 Å
a = 23.257 (1) Å	Cell parameters from 25 reflections
b = 8.715 (1) Å	θ = 8–18°
c = 14.668 (1) Å	µ = 0.44 mm^−1
β = 100.27 (1)°	T = 123 K
V = 2925.4 (4) Å^3	Prism, colourless
Z = 8	0.30 × 0.28 × 0.23 mm

Data collection

Enraf-Nonius CAD-4 diffractometer	3144 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.010
Graphite monochromator	θmax = 28.0°, θmin = 2.5°
ω scans	h = −30→30
Absorption correction: ψ scan (North et al., 1968)	k = 0→11
Tmin = 0.825, Tmax = 0.903	l = 0→19
4488 measured reflections	3 standard reflections every 200 reflections
3536 independent reflections	intensity decay: none

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.027	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.075	H-atom parameters constrained
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0403P)^2 + 2.3455P] where P = (Fo^2 + 2Fc^2)/3
3536 reflections	(Δ/σ)max = 0.001
191 parameters	Δρmax = 0.39 e Å^−3
0 restraints	Δρmin = −0.24 e Å^−3

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. The ω-scan width was (0.65 + 0.72 tanθ)° with a ω-scan rate of 0.69–3.35° min^-1. The scan angle was extended 25% on each side of each peak for background measurement. Refinement was by full-matrix least-squares methods. 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 (Ų)

	x	y	z	Uiso*/Ueq
Cl1	0.424247 (12)	0.96722 (3)	0.257182 (18)	0.01696 (8)
Cl2	0.427031 (13)	0.35991 (3)	0.30975 (2)	0.02068 (8)
O1	0.42030 (4)	1.20358 (10)	−0.01012 (6)	0.01646 (17)
O2	0.45633 (3)	0.86097 (10)	−0.02648 (5)	0.01527 (17)
H2	0.4924	0.8454	−0.0115	0.023*
C1	0.37522 (5)	1.12808 (13)	−0.02107 (7)	0.0133 (2)
C2	0.37216 (5)	0.96852 (13)	0.01914 (7)	0.0128 (2)
H2A	0.3526	0.9786	0.0743	0.015*
C3	0.33305 (5)	0.86561 (14)	−0.05103 (8)	0.0170 (2)
H3A	0.3495	0.8585	−0.1087	0.020*
H3B	0.3318	0.7610	−0.0252	0.020*
C4	0.27125 (5)	0.93128 (16)	−0.07304 (9)	0.0205 (2)
H4A	0.2481	0.8717	−0.1243	0.025*
H4B	0.2524	0.9197	−0.0180	0.025*
C5	0.27059 (5)	1.09797 (16)	−0.10004 (8)	0.0184 (2)
C6	0.22020 (5)	1.16329 (18)	−0.15196 (9)	0.0253 (3)
H6	0.1866	1.1013	−0.1706	0.030*
C7	0.21863 (6)	1.31690 (19)	−0.17651 (9)	0.0282 (3)
H7	0.1842	1.3588	−0.2124	0.034*
C8	0.26717 (6)	1.41022 (18)	−0.14896 (9)	0.0259 (3)
H8	0.2657	1.5159	−0.1652	0.031*
C9	0.31761 (6)	1.34814 (15)	−0.09776 (8)	0.0202 (2)
H9	0.3509	1.4114	−0.0788	0.024*
C10	0.31974 (5)	1.19192 (14)	−0.07382 (8)	0.0158 (2)
C11	0.43316 (5)	0.90157 (13)	0.05355 (7)	0.0126 (2)
H11	0.4584	0.9826	0.0885	0.015*
C12	0.43036 (5)	0.76496 (13)	0.11695 (7)	0.0127 (2)
C13	0.42647 (5)	0.78412 (13)	0.21029 (8)	0.0130 (2)
C14	0.42570 (5)	0.66120 (13)	0.27017 (8)	0.0144 (2)
H14	0.4240	0.6773	0.3337	0.017*
C15	0.42755 (5)	0.51429 (13)	0.23477 (8)	0.0152 (2)
C16	0.43076 (5)	0.48864 (14)	0.14231 (8)	0.0167 (2)
H16	0.4317	0.3872	0.1189	0.020*
C17	0.43255 (5)	0.61462 (13)	0.08477 (8)	0.0152 (2)
H17	0.4353	0.5980	0.0217	0.018*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.02097 (14)	0.01375 (14)	0.01607 (13)	0.00188 (10)	0.00302 (10)	−0.00337 (9)
Cl2	0.02614 (15)	0.01553 (14)	0.01995 (14)	−0.00333 (11)	0.00299 (11)	0.00555 (10)
O1	0.0163 (4)	0.0145 (4)	0.0181 (4)	−0.0006 (3)	0.0017 (3)	−0.0001 (3)
O2	0.0128 (4)	0.0202 (4)	0.0133 (4)	0.0015 (3)	0.0039 (3)	0.0012 (3)
C1	0.0144 (5)	0.0148 (5)	0.0109 (5)	0.0026 (4)	0.0026 (4)	−0.0009 (4)
C2	0.0118 (5)	0.0138 (5)	0.0125 (5)	0.0002 (4)	0.0013 (4)	0.0007 (4)
C3	0.0143 (5)	0.0174 (5)	0.0181 (5)	−0.0015 (4)	0.0000 (4)	−0.0016 (4)
C4	0.0135 (5)	0.0258 (6)	0.0212 (6)	−0.0027 (5)	0.0005 (4)	−0.0018 (5)
C5	0.0142 (5)	0.0272 (6)	0.0136 (5)	0.0044 (5)	0.0022 (4)	−0.0009 (4)
C6	0.0153 (5)	0.0402 (8)	0.0192 (6)	0.0070 (5)	−0.0005 (4)	−0.0024 (5)
C7	0.0239 (6)	0.0413 (8)	0.0183 (6)	0.0182 (6)	0.0009 (5)	0.0024 (5)
C8	0.0301 (7)	0.0292 (7)	0.0196 (6)	0.0155 (6)	0.0073 (5)	0.0063 (5)
C9	0.0224 (6)	0.0217 (6)	0.0178 (5)	0.0073 (5)	0.0066 (4)	0.0036 (5)
C10	0.0155 (5)	0.0200 (6)	0.0121 (5)	0.0055 (4)	0.0030 (4)	0.0010 (4)
C11	0.0126 (5)	0.0136 (5)	0.0116 (5)	0.0003 (4)	0.0015 (4)	0.0010 (4)
C12	0.0110 (5)	0.0137 (5)	0.0129 (5)	0.0002 (4)	0.0011 (4)	0.0006 (4)
C13	0.0116 (5)	0.0123 (5)	0.0145 (5)	0.0004 (4)	0.0009 (4)	−0.0020 (4)
C14	0.0131 (5)	0.0176 (6)	0.0123 (5)	−0.0010 (4)	0.0020 (4)	0.0005 (4)
C15	0.0155 (5)	0.0136 (5)	0.0158 (5)	−0.0013 (4)	0.0013 (4)	0.0039 (4)
C16	0.0192 (5)	0.0128 (5)	0.0175 (5)	−0.0012 (4)	0.0015 (4)	−0.0021 (4)
C17	0.0167 (5)	0.0162 (5)	0.0125 (5)	−0.0003 (4)	0.0017 (4)	−0.0016 (4)

Geometric parameters (Å, º)

Cl1—C13	1.7421 (11)	C6—H6	0.9500
Cl2—C15	1.7393 (12)	C7—C8	1.391 (2)
O1—C1	1.2239 (14)	C7—H7	0.9500
O2—C11	1.4210 (13)	C8—C9	1.3852 (17)
O2—H2	0.8400	C8—H8	0.9500
C1—C10	1.4889 (15)	C9—C10	1.4047 (17)
C1—C2	1.5172 (15)	C9—H9	0.9500
C2—C11	1.5336 (15)	C11—C12	1.5193 (15)
C2—C3	1.5353 (15)	C11—H11	1.0000
C2—H2A	1.0000	C12—C17	1.3968 (15)
C3—C4	1.5271 (16)	C12—C13	1.3980 (15)
C3—H3A	0.9900	C13—C14	1.3874 (15)
C3—H3B	0.9900	C14—C15	1.3851 (16)
C4—C5	1.5051 (19)	C14—H14	0.9500
C4—H4A	0.9900	C15—C16	1.3895 (16)
C4—H4B	0.9900	C16—C17	1.3900 (16)
C5—C6	1.3998 (16)	C16—H16	0.9500
C5—C10	1.4029 (17)	C17—H17	0.9500
C6—C7	1.385 (2)
C11—O2—H2	109.5	C9—C8—H8	120.2
O1—C1—C10	120.66 (10)	C7—C8—H8	120.2
O1—C1—C2	122.69 (10)	C8—C9—C10	120.19 (13)
C10—C1—C2	116.63 (10)	C8—C9—H9	119.9
C1—C2—C11	111.84 (9)	C10—C9—H9	119.9
C1—C2—C3	109.75 (9)	C5—C10—C9	120.43 (11)
C11—C2—C3	113.64 (9)	C5—C10—C1	120.83 (11)
C1—C2—H2A	107.1	C9—C10—C1	118.73 (11)
C11—C2—H2A	107.1	O2—C11—C12	111.99 (9)
C3—C2—H2A	107.1	O2—C11—C2	106.72 (8)
C4—C3—C2	110.22 (10)	C12—C11—C2	111.19 (9)
C4—C3—H3A	109.6	O2—C11—H11	109.0
C2—C3—H3A	109.6	C12—C11—H11	109.0
C4—C3—H3B	109.6	C2—C11—H11	109.0
C2—C3—H3B	109.6	C17—C12—C13	117.11 (10)
H3A—C3—H3B	108.1	C17—C12—C11	121.34 (10)
C5—C4—C3	112.48 (10)	C13—C12—C11	121.55 (10)
C5—C4—H4A	109.1	C14—C13—C12	122.55 (10)
C3—C4—H4A	109.1	C14—C13—Cl1	116.92 (8)
C5—C4—H4B	109.1	C12—C13—Cl1	120.51 (9)
C3—C4—H4B	109.1	C15—C14—C13	118.14 (10)
H4A—C4—H4B	107.8	C15—C14—H14	120.9
C6—C5—C10	118.29 (13)	C13—C14—H14	120.9
C6—C5—C4	120.26 (12)	C14—C15—C16	121.68 (10)
C10—C5—C4	121.44 (10)	C14—C15—Cl2	118.28 (9)
C7—C6—C5	121.01 (13)	C16—C15—Cl2	120.03 (9)
C7—C6—H6	119.5	C15—C16—C17	118.57 (11)
C5—C6—H6	119.5	C15—C16—H16	120.7
C6—C7—C8	120.47 (12)	C17—C16—H16	120.7
C6—C7—H7	119.8	C16—C17—C12	121.93 (10)
C8—C7—H7	119.8	C16—C17—H17	119.0
C9—C8—C7	119.60 (13)	C12—C17—H17	119.0
O1—C1—C2—C11	−13.37 (14)	C2—C1—C10—C9	168.49 (10)
C10—C1—C2—C11	167.92 (9)	C1—C2—C11—O2	−73.61 (11)
O1—C1—C2—C3	−140.45 (11)	C3—C2—C11—O2	51.34 (12)
C10—C1—C2—C3	40.84 (12)	C1—C2—C11—C12	163.99 (9)
C1—C2—C3—C4	−60.50 (12)	C3—C2—C11—C12	−71.06 (12)
C11—C2—C3—C4	173.44 (9)	O2—C11—C12—C17	−18.81 (14)
C2—C3—C4—C5	51.27 (13)	C2—C11—C12—C17	100.49 (12)
C3—C4—C5—C6	157.98 (11)	O2—C11—C12—C13	160.11 (10)
C3—C4—C5—C10	−22.40 (15)	C2—C11—C12—C13	−80.59 (12)
C10—C5—C6—C7	−0.36 (18)	C17—C12—C13—C14	1.02 (16)
C4—C5—C6—C7	179.28 (11)	C11—C12—C13—C14	−177.94 (10)
C5—C6—C7—C8	−0.8 (2)	C17—C12—C13—Cl1	179.35 (8)
C6—C7—C8—C9	0.94 (19)	C11—C12—C13—Cl1	0.39 (14)
C7—C8—C9—C10	0.01 (18)	C12—C13—C14—C15	−1.49 (16)
C6—C5—C10—C9	1.30 (17)	Cl1—C13—C14—C15	−179.87 (9)
C4—C5—C10—C9	−178.33 (11)	C13—C14—C15—C16	0.72 (17)
C6—C5—C10—C1	−178.10 (11)	C13—C14—C15—Cl2	179.62 (8)
C4—C5—C10—C1	2.27 (16)	C14—C15—C16—C17	0.46 (17)
C8—C9—C10—C5	−1.14 (17)	Cl2—C15—C16—C17	−178.43 (9)
C8—C9—C10—C1	178.27 (11)	C15—C16—C17—C12	−0.94 (17)
O1—C1—C10—C5	169.16 (11)	C13—C12—C17—C16	0.23 (16)
C2—C1—C10—C5	−12.10 (15)	C11—C12—C17—C16	179.19 (10)
O1—C1—C10—C9	−10.25 (16)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O1^i	0.84	2.04	2.8789 (11)	173
C11—H11···Cl1	1.00	2.73	3.0842 (11)	101
C17—H17···O2	0.95	2.47	2.8107 (14)	101
C14—H14···O1^ii	0.95	2.53	3.4547 (14)	164
C16—H16···O1^iii	0.95	2.46	3.3221 (14)	151

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