Ethyl 2-[5-(4-chloro­phen­yl)-1-(4-fluoro­phen­yl)-1H-pyrazol-3-yl]-4-methyl­thia­zole-5-carboxyl­ate

Wan-Sin Loh; Hoong-Kun Fun; R Venkat Ragavan; V Vijayakumar; S Sarveswari

doi:10.1107/S1600536810042066

. 2010 Oct 23;66(Pt 11):o2925. doi: 10.1107/S1600536810042066

Ethyl 2-[5-(4-chlorophenyl)-1-(4-fluorophenyl)-1H-pyrazol-3-yl]-4-methylthiazole-5-carboxylate

Wan-Sin Loh ^a,^‡, Hoong-Kun Fun ^a,^*,^§, R Venkat Ragavan ^b, V Vijayakumar ^b, S Sarveswari ^b

PMCID: PMC3009042 PMID: 21589099

Abstract

In the title compound, C₂₂H₁₇ClFN₃O₂S, the pyrazole ring is approximately planar with a maximum deviation of 0.001 (4) Å and makes dihedral angles of 4.95 (19), 35.78 (18) and 54.73 (18)° with the thiazole, fluorobenzene and chlorobenzene rings, respectively. In the crystal, intermolecular C—H⋯O hydrogen bonds link the molecules into chains along the a axis.

Related literature

For background to pyrazole derivatives and their antimicrobial activity, see: Ragavan et al. (2009 ▶, 2010 ▶). For bond-length data, see: Allen et al. (1987 ▶). For a related structure, see: Loh et al. (2010 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₂₂H₁₇ClFN₃O₂S
M _r = 441.90
Monoclinic,
a = 12.0296 (5) Å
b = 19.4428 (6) Å
c = 9.5847 (3) Å
β = 112.922 (1)°
V = 2064.74 (12) Å³
Z = 4
Mo Kα radiation
μ = 0.32 mm⁻¹
T = 100 K
0.42 × 0.17 × 0.08 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS, Bruker, 2009 ▶) T _min = 0.878, T _max = 0.976
30630 measured reflections
4697 independent reflections
3944 reflections with I > 2σ(I)
R _int = 0.043

Refinement

R[F ² > 2σ(F ²)] = 0.056
wR(F ²) = 0.163
S = 1.24
4697 reflections
273 parameters
H-atom parameters constrained
Δρ_max = 0.63 e Å⁻³
Δρ_min = −0.53 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); 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/S1600536810042066/fj2354sup1.cif

e-66-o2925-sup1.cif^{(22.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810042066/fj2354Isup2.hkl

e-66-o2925-Isup2.hkl^{(230.1KB, 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
C15—H15A⋯O2ⁱ	0.93	2.48	3.251 (5)	141

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Symmetry code: (i) Inline graphic .

Acknowledgments

HKF and WSL thank Universiti Sains Malaysia (USM) for the Research University Grant (1001/PFIZIK/811160). WSL thanks Malaysian Government and USM for the award of Research Fellowship. VV is grateful to the DST-India for funding through the Young Scientist Scheme (Fast Track Proposal).

supplementary crystallographic information

Comment

Antibacterial and antifungal activities of azoles are most widely studied and some of them are in clinical practice as anti-microbial agents. However, the azole-resistant strains had led to the development of new antimicrobial compounds. In particular pyrazole derivatives are extensively studied and used as antimicrobial agents. Pyrazole is an important class of heterocyclic compounds and many pyrazole derivatives are reported to have a broad spectrum of biological properties, such as anti-inflammatory, antifungal, herbicidal, anti-tumour, cytotoxic, molecular modelling and antiviral activities. Pyrazole derivatives also act as anti-angiogenic agents, A3 adenosine receptor antagonists, neuropeptide YY5 receptor antagonists, kinase inhibitor for treatment of type 2 diabetes, hyperlipidemia, obesity and thrombopiotinmimetics. Recently urea derivatives of pyrazoles have been reported as potent inhibitors of p38 kinase. 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 or 4-chloro substitution in the aryls of 1,5-diaryl pyrazoles. As part of our on-going research aiming the synthesis of new antimicrobial compounds, we have reported the synthesis of novel pyrazole derivatives and their microbial activities (Ragavan et al., 2009;2010).

The title compound consists of four rings, namely pyrazole (C1–C3/N1/N2), thiazole (C4/N3/C5/C6/S1), fluorophenyl (C11–C16/F1) and chlorophenyl (C17–C22/Cl1) rings (Fig. 1). The pyrazole ring is approximately planar with a maximum deviation of 0.001 (4) Å at atom C1 and makes dihedral angles of 4.95 (19), 35.78 (18) and 54.73 (18)° with the thiazole, fluorophenyl and chlorophenyl rings, respectively. Bond lengths (Allen et al., 1987) and angles are within the normal ranges and are comparable to the related structure (Loh et al., 2010).

In the crystal packing (Fig. 2), intermolecular C15—H15A···O2 hydrogen bonds link the molecules into one-dimensional chains along the a axis.

Experimental

The compound has been synthesized using the method available in the literature (Ragavan et al., 2010) and recrystallized using the ethanol-chloroform 1:1 mixture. Yield: 81%. M.p.: 411.3–413 K.