2-Methyl-2-(4-nitro­phenyl­sulfanyl)­propanoic acid

Gabriel Navarrete-Vázquez; Rafael Villalobos-Molina; Samuel Estrada-Soto; Rolffy Ortiz-Andrade; Hugo Tlahuext

doi:10.1107/S1600536807062678

. 2007 Dec 6;64(Pt 1):o91. doi: 10.1107/S1600536807062678

2-Methyl-2-(4-nitrophenylsulfanyl)propanoic acid

Gabriel Navarrete-Vázquez ^a, Rafael Villalobos-Molina ^b, Samuel Estrada-Soto ^a, Rolffy Ortiz-Andrade ^a, Hugo Tlahuext ^c,^*

PMCID: PMC2915046 PMID: 21200968

Abstract

The title compound, C₁₀H₁₁NO₄S, is of interest with respect to its biological activity. The molecules are linked into centrosymmetric dimers by intermolecular O—H⋯O hydrogen bonds and the dimers are further connected into chains by weak C—H⋯O interactions.

Related literature

For related literature on fibrate structures and biological activity, see: Henry et al. (2003 ▶); Rath et al. (2005 ▶); Djinović et al. (1989 ▶); Thorp (1962 ▶); Thorp & Waring (1962 ▶); Miller & Spence (1998 ▶); Forcheron et al. (2002 ▶). For related literature, see: Bernstein et al. (1995 ▶); Desiraju (2002 ▶).

Experimental

Crystal data

C₁₀H₁₁NO₄S
M _r = 241.26
Triclinic,
a = 6.9382 (8) Å
b = 9.4500 (11) Å
c = 9.6395 (11) Å
α = 66.371 (2)°
β = 87.995 (2)°
γ = 88.298 (2)°
V = 578.60 (12) Å³
Z = 2
Mo Kα radiation
μ = 0.28 mm⁻¹
T = 273 (2) K
0.32 × 0.23 × 0.18 mm

Data collection

Bruker SMART CCD area detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2003 ▶) T _min = 0.92, T _max = 0.95
5660 measured reflections
2036 independent reflections
1718 reflections with I > 2σ(I)
R _int = 0.020

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.123
S = 1.08
2036 reflections
148 parameters
H-atom parameters constrained
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Data collection: SMART (Bruker, 2000 ▶); cell refinement: SAINT-Plus NT (Bruker, 2000 ▶); data reduction: SAINT-Plus NT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 ▶); molecular graphics: SHELXTL-NT (Bruker, 2000 ▶); software used to prepare material for publication: PLATON (Spek, 2003 ▶) and publCIF (Westrip, 2007 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536807062678/ln2010sup1.cif

e-64-00o91-sup1.cif^{(16KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807062678/ln2010Isup2.hkl

e-64-00o91-Isup2.hkl^{(100.1KB, hkl)}

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
O4—H4⋯O3ⁱ	0.82	1.84	2.656 (3)	175
C2—H2⋯O2ⁱⁱ	0.93	2.46	3.211 (3)	138

Open in a new tab

Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

This work was supported by the Consejo Nacional de Ciencia y Tecnología (CONACyT) under grant No. 3562P-E and PROMEP-SEP UAEMOR-PTC-131 (GNV).

supplementary crystallographic information

Comment

Fibrates, such as bezafibrate, clofibric acid and fenofibrate (Henry et al., 2003; Rath et al., 2005; Djinović et al., 1989), which are ligands for the nuclear receptor PPAR (peroxisome proliferator-activated receptor), are used as therapeutic agents in the treatment of hyperlipidemia, heart disease and diabetic complications in humans. The fibrates are a widely used class of lipid-modifying agents that decrease plasma triglycerides (Thorp, 1962; Miller & Spence, 1998; Forcheron et al., 2002). The fibric acid pharmacophore has been of interest to medicinal chemists ever since the initial discovery that ethyl chlorophenoxyisobutyrate possessed hypolipidemic properties (Thorp & Waring, 1962).

In order to assist our knowledge about the electronic and steric requirements for such compounds to to show antihyperlipidemic activity, we have determined the crystal structure of the title compound, (I), which is an analogue of clofibric acid with a thioisobutirate side chain. A view of the molecular structure of (I) and hydrogen bonded dimers is given in Fig. 1. The crystal structure is permeated by strong O—H···O hydrogen-bonding interactions, as well as weak C—H···O interactions (Tablel 1) (Desiraju, 2002). The O—H···O hydrogen bonding interactions form centrosymmetric dimers and generate rings that can be described as having a graph set motif of R₂²(8) (Bernstein et al., 1995).

Experimental

A mixture of 4-nitrothiophenol (1.0 g, 6.40 mmol), potassium carbonate (1.94 g, 14.1 mmol) in acetonitrile, was added dropwise to 1.04 ml of ethyl 2-bromo-2-methylpropionate (1.37 g, 7.04 mmol). The mixture was stirred and heated under reflux for 6 h. After that, the mixture was poured onto cold water. The resulting oil was treated with a mixture of tetrahydrofuran/methanol/H₂O (3:2:1, v/v/v, 6 ml/mmol), and LiOH was added (5 equiv). The mixture was stirred at room temperature for 3 h. Then, HCl solution (10% v/v) was added, and most of the organic solvents removed in vacuo. The partly solid residue was extracted with CH₂Cl₂ (3 x 10 ml), dried with Na₂SO₄, filtered, and concentrated in vacuo to give a yellow solid (m.p. 394.9 K). Single crystals of (I) were obtained from acetonitrile.