Crystal structure of ethyl (6-hydroxy-1-benzofuran-3-yl)acetate sesquihydrate

The crystal structure of ethyl (6-hydroxy-1-benzofuran-3-yl)acetate sesquihydrate exhibits a one-dimensional hydrogen-bond motif consisting of (12) rings joined at water molecules located on a twofold rotation axis.

In the title hydrate, C 12 H 12 O 4 Á1.5H 2 O, one of the water molecules in the asymmetric unit is located on a twofold rotation axis. The molecule of the benzofuran derivative is essentially planar (r.m.s. deviation for the non-H atoms = 0.021 Å ), with the ester group adopting a fully extended conformation. In the crystal, O-HÁ Á ÁO hydrogen bonds between the water molecules and the hydroxy groups generate a centrosymmetric R 6 6 (12) ring motif. These R 6 6 (12) rings are fused, forming a one-dimensional motif extending along the c-axis direction.

Chemical context
Furan heterocycles are of interest for synthetic chemists as they possess various pharmacological and biological activities including antituberculosis (Tawari et al., 2010), anti-inflammatory (Shin et al., 2011) and antibacterial (Kirilmis et al., 2008) activity. Substituted benzofurans have found applications as fluorescent sensors (Oter et al., 2007), anti-oxidants, brightening agents and drugs. Moreover, benzofuran carboxylic acid ethyl ester also exhibits selective cytotoxicity against a tumorigenic cell line (Hayakawa et al., 2004). In view of the above facts, and as a continuation of our structural studies on benzofurans (Arunakumar, Krishnaswamy et al., 2014;Arunakumar, Desai Nivedita et al., 2014), the title compound has been synthesized, characterized by FT IR, 1 H NMR and LC-MS methods and its crystal structure determined.

Structural commentary
The title compound crystallizes as a 1.5-hydrate with one of the symmetry-independent water molecules occupying a special position of C 2 symmetry. The molecular structure of the title compound is shown in Fig. 1. The molecule is almost planar (r.m.s. deviation for the non-H atoms = 0.021 Å ) and the ethyl acetate fragment adopts a fully extended conformation.

Supramolecular features
Hydrogen bonds (Table 1) between two hydroxy groups and four water molecules generate a centrosymmetric R 6 6 (12) ring motif. The rings are fused at the position of the O5 atoms, i.e. through water molecules located at special positions. In effect, two antiparallel chains of hydrogen bonds are formed that are fused at every fourth O atom and which propagate along the crystallographic c-axis (Fig. 2). In the crystal, the components are connected into a three-dimensional network through additional hydrogen bonds between the water molecule in a general position and the ester carbonyl group. In addition to strong hydrogen bonds, weaker C-HÁ Á Á interactions are observed between the methylene group H atoms and the benzene and furan rings ( Fig. 3 and Table 1).

Synthesis and crystallization
2-(6-Hydroxy-1-benzofuran-3-yl)acetic acid (2.0 g, 0.010 mmol) was taken in a round-bottomed flask containing ethanol (10 mL). Concentrated sulfuric acid (1 mL) was added and the reaction mixture was refluxed for 4 h at 353 K. After completion of the reaction, the reaction mixture was poured into ice-cold water and extracted to an ethyl acetate layer. The organic layer was washed with water followed by brine solution and dried over anhydrous sodium sulfate. The organic layer was concentrated under vacuum, giving a reddish residue. The residue was purified by column chromatography using silica gel (60-120 mesh) and ethyl acetate/petroleum ether (2:8) as eluent, affording a colourless crystalline product. Crystals suitable for X-ray analysis were formed by slow evaporation of the solution of the compound in ethyl acetate and petroleum ether (3:2) at room temperature. As the product had been water worked-up, water might have entered in the solid interstices during work-up.

Refinement
Crystal data, data collection and structure refinement details are summarized in The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level.

Figure 3
The C-HÁ Á Á interactions (dashed lines) in the title compound.
were located from a difference Fourier map. The H atom bound to O5 was freely refined and those bound to O2 had the O-H distances restrained to 0.85 (2) Å . The remaining C/Obound H atoms were fixed geometrically (C-H = 0.93-0.97 and O-H = 0.82 Å ) and allowed to ride on their parent atoms with U iso (H) = 1.5U eq (C,O) for methyl and hydroxy H atoms, and 1.2U eq (C) for other H atoms.    (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Special details
Experimental. Thin-layer chromatography (TLC) was carried out on Merck pre-coated silica gel plates to monitor the progress of the reaction. The FT-IR spectra were recorded as KBr pellets using JASCO FT-IR-4100 spectrophotometer in the range 4000-400 cm -1 at a resolution of 2 cm -1 . 1 H NMR spectra were recorded in CDCl 3 and DMSO-d 6 on a JEOL-400 MHz NMR instrument. Chemical shifts are reported in δ values in parts per million relative to TMS. Mass spectral data were obtained on an Agilent LC-MS column C-18 instrument. The IR spectrum of (I) exhibits strong bands at 1686 cm -1 and 1193 cm -1 due to C=O and C-O stretchings, respectively. A single band appearing at 3340 cm -1 is due to OH group stretching. Appearance of bands in the range 3011-2907 cm -1 is due to aromatic stretching and bands in the range 2970-2815 cm -1 are due to C-H stretching, thus confirming the presence of the saturated hydrocarbons in (I).
The 1 H NMR spectrum of (I) shows peaks at δ 9.53 (s, 1H, Ar-OH), 6.69 (s, 1H, furan-H), 7.35-7.33 (d, 1H, Ar-H), 6.88-6.87 (d, 1H, Ar-H), 6.75-6.72 (q, 1H, Ar-H), 4.12-4.07 (q, 2H, OCH 2 ), 3.34 (s, 2H, CH 2 ), 1.12-1.17 (t, 3H, CH 3 ). The LC-MS spectrum shows the appearance of molecular ion peaks at m/z 221 and 222 values, confirming the structure of the compound. Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes. 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 > 2σ(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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq O16 0.74036 (