5-Methoxy­methyl-4-phen­oxy-1H-pyrazol-3-ol

Tara Shahani; Hoong-Kun Fun; R Venkat Ragavan; V Vijayakumar; S Sarveswari

doi:10.1107/S1600536809050302

. 2009 Nov 28;65(Pt 12):o3249–o3250. doi: 10.1107/S1600536809050302

5-Methoxymethyl-4-phenoxy-1H-pyrazol-3-ol

Tara Shahani ^a, Hoong-Kun Fun ^a,^*,^‡, R Venkat Ragavan ^b, V Vijayakumar ^b, S Sarveswari ^b

PMCID: PMC2971925 PMID: 21578948

Abstract

In the title compound, C₁₁H₁₂N₂O₃, the pyrazole ring system is essentially planar [maximum deviation = 0.002 (2) Å] and forms a dihedral angle of 66.93 (9)° with the benzene ring. In the crystal packing, pairs of intermolecular N—H⋯O and O—H⋯N hydrogen bonds connect neighbouring molecules into dimers, generating R ₂ ²(10) and R ₂ ²(8) ring motifs, respectively. The crystal structure is further stabilized by C—H⋯π interactions.

Related literature

For the biological activity of pyrazoles, see: Genin et al. (2000 ▶); Hsu et al. (1956 ▶); Jung et al. (2002 ▶); Kudo et al. (1999 ▶); Singh et al. (1978 ▶); Skipper et al. (1955 ▶); Storer et al. (1999 ▶); Tewari & Mishra (2001 ▶). For pyrazole derivatives, see: Baraldi et al. (2003 ▶); Brown et al. (2004 ▶); Duma et al. (2000 ▶); Heerding (2003 ▶); Qiao et al. (2003 ▶); Stamford & Wu (2004 ▶). For a related structure, see: Goh et al. (2009 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For bond-length data, see: Allen et al. (1987 ▶). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986 ▶). graphic file with name e-65-o3249-scheme1.jpg

Experimental

Crystal data

C₁₁H₁₂N₂O₃
M _r = 220.23
Monoclinic,
a = 8.8876 (5) Å
b = 10.3031 (5) Å
c = 12.0083 (6) Å
β = 100.917 (3)°
V = 1079.7 (1) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.69 × 0.57 × 0.18 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T _min = 0.934, T _max = 0.983
14470 measured reflections
3433 independent reflections
2373 reflections with I > 2σ(I)
R _int = 0.032

Refinement

R[F ² > 2σ(F ²)] = 0.058
wR(F ²) = 0.138
S = 1.10
3433 reflections
193 parameters
All H-atom parameters refined
Δρ_max = 0.45 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809050302/lh2960sup1.cif

e-65-o3249-sup1.cif^{(17.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809050302/lh2960Isup2.hkl

e-65-o3249-Isup2.hkl^{(168.4KB, 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
N2—H1N2⋯O2ⁱ	0.91 (2)	1.89 (2)	2.7778 (18)	165.7 (19)
O3—H1O3⋯N1ⁱⁱ	0.92 (2)	1.74 (2)	2.6663 (18)	176 (2)
C3—H3A⋯Cg1ⁱⁱⁱ	0.94 (2)	2.77 (3)	2.73	147.6 (18)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) . Cg1 is the centroid of the C1–C6 benzene ring.

Acknowledgments

HKF and TSH thank Universiti Sains Malaysia (USM) for the Research University Golden Goose Grant (1001/PFIZIK/811012). VV is grateful to the DST-India for funding through the Young Scientist Scheme (Fast Track Proposal).

supplementary crystallographic information

Comment

Pyrazoles are an important class of heterocyclic compounds and many pyrazole derivatives have a broad spectrum of biological activities such as anti-inflammatory (Singh et al., 1978; Tewari & Mishra, 2001), anti-viral (Genin et al., 2000; Storer et al., 1999), anti-tumor (Hsu et al., 1956; Skipper et al., 1955), and herbicidal (Jung et al., 2002; Kudo et al., 1999) activities. Recently urea derivatives of pyrazole been reported as potent inhibitors of P³⁸ kinase (Duma, 2000), On the other hand, pyrazole derivatives are anti-angiogenic agent (Qiao et al., 2003), A3 adenosine receptor antagonist (Baraldi et al., 2003), neuropeptide YY5 receptor antagonists (Stamford & Wu, 2004) and kinase inhibitor for the treatment of type 2 diabetes, hyperlipidemia and obesity (Brown et al., 2004) as well as thrombopiotinmimetics (Heerding, 2003). Since the high electronegativity of halogens (particularly chlorine and fluorine) in the aromatic part of the drug molecules play an important role in enhancing their biological activity, we are interested to have 4-fluoro and 4-chloro substituted phenyl rings in the aromatic part of a 1,5-diaryl pyrazole. As part of our on going research programme aiming at the synthesis of new anti-microbial compounds, herein we report the crystal structure of a novel pyrazole derivative.

In the crystal structure (Fig. 1), the pyrazole ring system (C7/C8/N2/N1/C11) is approximately planar, with a maximum deviation of 0.002 (2) Å for atom C11. The dihedral angle formed between the mean plane of pyrazole ring and the benzene ring (C1–C6) is 66.93 (9)°. The bond lengths (Allen et al., 1987) and angles are within normal ranges and comparable to a closely related structure (Goh et al., 2009).

In the crystal packing (Fig. 2), pairs of intermolecular N2—H1N2···O2ⁱ and O3—H1O3···N1ⁱⁱ hydrogen bonds (Table 1) connect neighbouring molecules, into dimers, generating R₂²(10) and R₂²(8) ring motifs (Bernstein et al., 1995), respectively. The crystal structure is further stabilized by C—H···π interactions (Table 1), involving the C1–C6 (centroid Cg1) benzene ring.

Experimental

LiHMDS (19.4 ml, 1.0 min THF, 19.4 mmol) was added quickly to the solution of oxyacetic acid ethyl ester (1.0 g, 5.5 mmol) in toluene (15.0 ml) using syringe at 195 K with agitation and the anion formed was allowed to stand for approximately 1 min, and then 2-methoxyacetyl chloride (1.0 ml, 13.8 mmol) was added into the lot with stirring. Reaction mixture was removed from acetone-dry ice bath and stirred for 10 min then acetic acid (2.0 ml) was added with stirring. Ethanol (15.0 ml) and hydrazine hydrate (1.5 ml, 44.0 mmol) was added and refluxed for 10 min. Reaction mixture was concentrated to dryness under reduced pressure and redissolved in ethyl acetate. The organic layer was washed with saturated brine solution, dried over Na₂SO₄ and evaporated under reduced pressure. Crude product was purified by column chromatography using a mixture of 1:99 methanol and ethylacetate. Pale yellow solid was obtained. Mp. 418.8–419.8 K. Yield: 57%.