2-(5-Fluoro-3-isopropyl­sulfanyl-1-benzofuran-2-yl)acetic acid

Pil Ja Seo; Hong Dae Choi; Byeng Wha Son; Uk Lee

doi:10.1107/S1600536811044436

. 2011 Oct 29;67(Pt 11):o3112. doi: 10.1107/S1600536811044436

2-(5-Fluoro-3-isopropylsulfanyl-1-benzofuran-2-yl)acetic acid

Pil Ja Seo ^a, Hong Dae Choi ^a, Byeng Wha Son ^b, Uk Lee ^b,^*

PMCID: PMC3247497 PMID: 22220115

Abstract

The title compound, C₁₃H₁₃FO₃S, was prepared by alkaline hydrolysis of ethyl 2-(5-fluoro-3-isopropylsulfanyl-1-benzofuran-2-yl)acetate. In the crystal, the carboxy groups are involved in intermolecular O—H⋯O hydrogen bonds, which link the molecules into centrosymmetric dimers. These dimers are further packed into stacks along the b axis by a slipped π–π interaction between the furan and benzene rings of neighbouring molecules [centroid–centroid distance = 3.727 (2) Å, interplanar distance = 3.465 (2) Å and slippage = 1.373 (2) Å]. The crystal structure also exhibits a short S⋯O contact [S⋯O = 3.219 (2) Å].

Related literature

For the pharmacological activity of benzofuran compounds, see: Aslam et al. (2009 ▶); Galal et al. (2009 ▶); Khan et al. (2005 ▶). For natural products with benzofuran rings, see: Akgul & Anil (2003 ▶); Soekamto et al. (2003 ▶). For the crystal structures of related compounds, see: Choi et al. (2009a ▶,b ▶).

Experimental

Crystal data

C₁₃H₁₃FO₃S
M _r = 268.29
Monoclinic,
a = 10.6101 (2) Å
b = 8.5749 (1) Å
c = 13.6083 (2) Å
β = 97.149 (1)°
V = 1228.47 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.27 mm⁻¹
T = 296 K
0.34 × 0.26 × 0.16 mm

Data collection

Bruker SMART APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.913, T _max = 0.958
11299 measured reflections
2812 independent reflections
2535 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.032
wR(F ²) = 0.084
S = 1.08
2812 reflections
169 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and DIAMOND (Brandenburg, 1998 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811044436/vm2132sup1.cif

e-67-o3112-sup1.cif^{(22.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811044436/vm2132Isup2.hkl

e-67-o3112-Isup2.hkl^{(138.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811044436/vm2132Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O3ⁱ	0.84 (2)	1.79 (2)	2.6257 (14)	177 (2)

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Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

Substituted benzofuran derivatives have attracted considerable interest in view of their valuable pharmacological properties such as antibacterial and antifungal, antitumor and antiviral, and antimicrobial activities (Aslam et al., 2009, Galal et al., 2009, Khan et al., 2005). These benzofuran derivatives occur in a wide range of natural products (Akgul & Anil, 2003; Soekamto et al., 2003). As a part of our ongoing study of 2-(3-alkylsulfanyl-5-fluoro-1-benzofuran-2-yl)acetic acid analogues (Choi et al., 2009a,b), we report herein the crystal structure of the title compound.

In the title molecule (Fig. 1), the benzofuran unit is essentially planar, with a mean deviation of 0.014 (2) Å from the least-squares plane defined by the nine constituent atoms. In the crystal structure, the carboxyl groups are involved in intermolecular O—H···O hydrogen bonds (Table 1 & Fig. 2), which link the molecules into centrosymmetric dimers. These dimers are further packed into stacks along the b axis by a weak slipped π–π interaction between the furan and benzene rings of neighbouring molecules, with a Cg1···Cg2ⁱⁱⁱ distance of 3.727 (2) Å and an interplanar distance of 3.465 (2) Å resulting in a slippage of 1.373 (2) Å (Cg1 and Cg2 are the centroids of the C1/C2/C7/O1/C8 furan ring and the C2–C7 benzene ring, respectively). The crystal packing (Fig. 2) is further stabilized by an intermolecular S···O contact between the S atom and the O atom of the hydroxyl group [S1···O2ⁱⁱ = 3.219 (2) Å].

Experimental

Ethyl 2-(5-fluoro-3-isopropylsulfanyl-1-benzofuran-2-yl)acetate (355 mg, 1.2 mmol) was added to a solution of potassium hydroxide (337 mg. 6 mmol) in water (10 ml) and methanol (10 ml), and the mixture was refluxed for 5 h, then cooled. Water (10 ml) was added, and the solution was extracted with dichloromethane. The aqueous layer was acidified to pH 1 with concentrated hydrochloric acid and then extracted with chloroform, dried over magnesium sulfate, filtered and concentrated at reduced pressure. The residue was purified by column chromatography (ethyl acetate) to afford the title compound as a colorless solid [yield 89%, m.p. 399–400 K; R_f = 0.58 (ethyl acetate)]. Single crystals suitable for X-ray diffraction were prepared by slow evaporation of a solution of the title compound in diisopropyl ether at room temperature.