4-(2-Hydroxyethoxy)phenol

The asymmetric unit of the title compound, C8H10O3, contains four molecules, which differ in the orientation of the hydroxyethyl group [O—C—C—O torsion angles = −168.89 (17), 72.9 (2), −65.8 (2) and 71.8 (2)°], as well as the orientation of the hydroxy H atoms. Furthermore, the crystal structure displays two different types of strong hydrogen bond. The first is between an alcohol O—H and another alcohol O atom, and the second between an alcohol O—H group and an ether O atom. Additional weak hydrogen bonds between C—H groups and ether O atoms stabilize the structure.

The asymmetric unit of the title compound, C 8 H 10 O 3 , contains four molecules, which differ in the orientation of the hydroxyethyl group [O-C-C-O torsion angles = À168.89 (17), 72.9 (2), À65.8 (2) and 71.8 (2) ], as well as the orientation of the hydroxy H atoms. Furthermore, the crystal structure displays two different types of strong hydrogen bond. The first is between an alcohol O-H and another alcohol O atom, and the second between an alcohol O-H group and an ether O atom. Additional weak hydrogen bonds between C-H groups and ether O atoms stabilize the structure.

Related literature
For the synthesis of the title compound, see: Read & Miller (1932). For its biological activity, see: Smit et al. (1992). For its use in the synthesis of biologically active materials, see: Ding et al. (2009);Pitterna et al. (2004); Petrović & Brü ckner (2011). For its application in polymer synthesis, see: Nakano et al. (2000); Kaneda et al. (2004); Xi et al. (2010). For its use as a substrate for dye synthesis, see: Kelly (1996). For information about the cuprate, used for synthesis, see: Normant et al. (1980). For its reactivity, see: Semmelhack et al. (1985). H atoms treated by a mixture of independent and constrained refinement Á max = 0.21 e Å À3 Á min = À0.27 e Å À3 Table 1 Selected torsion angles ( ). Although the synthesis of the title compound, Scheme 1, has been known for about 80 years (Read & Miller, 1932), its crystal structure has never been reported. It has been used in syntheses of biologically active materials such as anti-cancer agents (Ding et al., 2009) as it is toxic to melanoma cells (Smit et al., 1992). It has also been used for the synthesis of an acaricide and insecticide substance (Pitterna et al., 2004) and for the synthesis of steroid precursors (Petrović & Brückner, 2011). Further uses are as a monomer in polymer synthesis including liquid crystalline polymers (Nakano et al., 2000) and coating rubbers (Kaneda et al., 2004), in the synthesis of a surface active piperazine derivative (Xi et al., 2010) and as a starting material for the synthesis of liquid-crystalline dyes (Kelly, 1996). We intended to do a 1,4 addition of a Normant cuprate (Normant et al., 1980) to 1,4-dioxaspiro[4.5]deca-6,9-dien-8-one, but under the conditions applied we observed the title compound as the only product. A similar observation has been made (Semmelhack et al., 1985) in the reaction of the same quinone with nBuLi. The intended synthesis along with the actual reaction is shown in Fig. 1.

Experimental
The title compound was synthesized unplanned by the following procedure. A solution of 678 mg CuBr*SMe 2 (3.30 mmol, 1.10 eq.) in 7 ml of dimethyl sulfide and 15 ml of ABS.THF was added at -30°C to a solution of 2.20 ml of methyl magnesium chloride (3 M in THF, 494 mg, 6.60 ml, 2.20 eq.) and the mixture was stirred at this temperature for 1 h. Then the mixture was cooled to -50°C and a solution of 460 mg 1,4-dioxaspiro[4.5]deca-6,9-dien-8-one (3.00 mmol, 1.00 eq.) in 5 ml of ABS.THF was added slowly to this mixture. Stirring was continued at this temperature for 15 h, then 11 ml of saturated ammonium chloride solution were added and the mixture was warmed to room temperature. Then air was bubbled through the solution for 1 h, the phases were separated and the aqueous phase was extracted with ethyl acetate (4 × 10 ml). The combined organic layers were dried over sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by column chromatography (cyclohexane/ethyl acetate = 5:1) to yield the product as colorless crystals (361 mg

Refinement
All H atoms were located in a difference electron density map. H atoms bound to carbon were refined using a riding model with aromatic C-H = 0.95 Å, secondary C-H = 0.99 Å, and with U iso (H) = 1.2U eq (C). The coordinates of the hydroxyl H atoms were refined freely with O-H distance retraints (0.84 (1) Å) and U iso (H) = 1.5U eq (O). Additionally 1,2 and 1,3 distance restraints (SADI) were used for the refinement of the hydroxyl group (for O-H and C-H(O) distance).   Least-squares fit of the four crystallographic independent molecules (fitted atoms O4, O8 and the C atoms of the phenyl ring).

Figure 4
Packing diagram showing the strong and weak hydrogen bonds.

4-(2-Hydroxyethoxy)phenol
Special details Experimental. NMR spectra were recorded on a Bruker AM 400 spectrometer as solutions. Chemical shifts are expressed in parts per million (p.p.m., δ) downfield from tetramethylsilane (TMS) and are referenced to residual solvent peaks. The descriptions of signals include: m = multiplet, m c = centered multiplet, bs = broad singlet. The spectra were analyzed as first order patterns. The signal structure in the 13 C NMR was analyzed by DEPT and is described as follows: + = primary or tertiary C-atom (positive DEPT signal), -= secondary C-atom (negative DEPT signal) and C q = quaternary C-atom (no DEPT signal). MS(EI) (electron impact mass spectrometry) was performed by using a FINNIGAN MAT 90 (70 eV). The mass peak [M] + and characteristic fragment peaks are given as mass to charge ratio (m/z) and the intensity of the signals were indicated in percent, relative to the intensity of the base signal (100%). IR (infrared spectroscopy) was recorded on a FT-IR Bruker alpha and intensities of the signals are characterized as follows: vs (very strong, 0-10% transmission), s (strong, 11-30% transmission), m (medium, 31-70% transmission), w (weak, 71-90% transmission) and vw (very weak, 91-100% transmission). Solvents, reagents and chemicals were purchased from Aldrich, Acros and Merck. All solvents, reagents and chemicals were used as purchased. R f (cyclohexane/ethyl acetate = 1:1) = 0.30. -1 H NMR (400 MHz, acetone-D 6 ): δ/p.p.m. = 3.80-3.84 (m, 2H, 2 × CH 2 ), 3.92-3.97 (m, 3H, OH, 2 × CH 2 ), 6.76 (m c , 4H, 4 × CH Ar ), 7.89 (bs, 1H, OH Ar ). Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.