5-(1-Cyclo­hexen-1-yl)-3-(4-methoxy­phen­yl)isoxazole

Gabriel Vallejos; Margarita Gutierrez; Luis Astudillo; Iván Brito; Alejandro Cárdenas

doi:10.1107/S1600536809010903

. 2009 Mar 28;65(Pt 4):o920. doi: 10.1107/S1600536809010903

5-(1-Cyclohexen-1-yl)-3-(4-methoxyphenyl)isoxazole

Gabriel Vallejos ^a, Margarita Gutierrez ^b, Luis Astudillo ^b, Iván Brito ^c,^*, Alejandro Cárdenas ^d

PMCID: PMC2968997 PMID: 21582622

Abstract

In the title compound, C₁₆H₁₇NO₂, the isoxazole ring makes a dihedral angle of 14.81 (13)° with the 4-methoxyphenyl ring. Two atoms of the cyclohexene ring are disordered over two almost equally occupied positions [0.526 (13)/0.474 (13)]. The molecular structure features a short intramolecular C—H⋯O contact.

Related literature

For background to isoxazoles, see: Melo (2005 ▶). For their biological activities, see: Narlawar et al. (2008 ▶); Patrick et al. (2007 ▶); Taldone et al. (2008 ▶); Rizzi et al. (2008 ▶); Velaparthi et al. (2008 ▶). For synthetic details, see: Hansen et al. (2005 ▶).

Experimental

Crystal data

C₁₆H₁₇NO₂
M _r = 255.31
Triclinic,
a = 5.8690 (11) Å
b = 10.9646 (19) Å
c = 11.481 (5) Å
α = 77.889 (2)°
β = 75.728 (5)°
γ = 80.262 (9)°
V = 694.7 (4) Å³
Z = 2
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 295 K
0.20 × 0.16 × 0.10 mm

Data collection

Nonius KappaCCD area-detector diffractometer
Absorption correction: none
4217 measured reflections
2467 independent reflections
2023 reflections with I > 2σ(I)
R _int = 0.076

Refinement

R[F ² > 2σ(F ²)] = 0.055
wR(F ²) = 0.135
S = 1.14
2467 reflections
192 parameters
H-atom parameters constrained
Δρ_max = 0.14 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: COLLECT (Nonius, 2000 ▶); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997 ▶); data reduction: DENZO-SMN; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶) and PLATON (Spek, 2009 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809010903/bt2910sup1.cif

e-65-0o920-sup1.cif^{(20.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809010903/bt2910Isup2.hkl

e-65-0o920-Isup2.hkl^{(118.7KB, 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
C6—H6⋯O1	0.93	2.48	2.811 (3)	101

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Acknowledgments

We thank the Spanish Research Council (CSIC) for providing us with a free-of-charge licence for the CSD system.

supplementary crystallographic information

Comment

Isoxazoles are molecules of great interest in chemistry because many natural products have been synthesized starting from these ones (Melo, 2005), and also because these compounds exhibit diverse biological activities [i.e.antiprotozoalactivities (Patrick et al., 2007), Hsp90 superchaperone complex inhibitors (Taldone et al., 2008), tau aggregation inhibitors for treatment of Alzheimer's disease (Narlawar et al., 2008) Mycobacteriumtuberculosis pantothenate synthetase inhibitors (Velaparthi et al., 2008), and neuronal nicotinic acetylcholine receptors agonist (Rizzi et al., 2008)]. This compound was evaluated against acetilcholinesterase (AChE) enzyme, it showed moderate inhibitory activity toward AChE, with a IC₅₀of 2.16 mM. For these reasons, the synthesis and structure of isoxazole is still of great interest. We report here the crystal structure of the title compound, Fig.1. The planar isoxazole makes a dihedral angle of 14.85 (13)° with the 4-methoxyphenyl ring and 25.1 (3)° and 14.1 (3)° with the cyclohexene groups, respectively. The molecular structure is stabilized by one intramolecular C—H··· O hydrogen bond, Table 1.

Experimental

Melting points were recorded on an Electrothermal 9100 instrument and are uncorrected; IR spectra were obtained on a Nicolet Nexus 470-FTIR spectrometer as potassium bromide pellets and are reported in wavenumbers (cm^-1). ¹H and ¹³C NMR spectra were measured on a Bruker AM-400 spectrometer (400 MHz), using CDCl₃ assolvent. TMS was used as an internal standard. Chemical shifts (d) and J values are reported in p.p.m. and Hz, respectively. Reaction progress was monitored by means of thin-layer chromatography using Merck Kieselgel 60 (230–240 mesh). All reagents were purchased from Merck, Sigma and Aldrich Chemical Co. and used without further purification. Solvents were dried and distilled prior to use.

5-(1-cyclohexen-1-yl)-3-(4-methoxyphenyl)isoxazole was obtained using the method described by Hansen et al. (2005), starting from 4-methoxybenzaldehyde (2.72 g, 20 mmol), hydroxylamine hydrochloride (1.46 g, 21 mmol), chloramine-T trihydrate (5.9 g, 21 mmol) and 1-Ethynylcyclohexene (2.23 g,21 mmol) (See Fig. 2), giving off-white solid; mp 76–78 °C, yield 93%. Yellow block-shaped crystals of (I) suitable for X-ray analysis were grown from a hexane/EtOAc solution (1:1 v/v) at 298 K over a period of a few days. RMN-¹H(CDCl₃, 400 MHz): d 7,74 (d, J= 8.9 Hz, 2H); 6,96 (d, J= 8.9 Hz, 2H); 6,64 (m, 1H); 6,32 (s,1H); 3,85 (s, 1H); 2,37 (m, 2H); 2,26 (m, 2H); 1,77 (m, 2H); 1,69 (m, 2H). RMN-¹³C(CDCl₃, 100 MHz): d 171.35, 161.99,160.83, 129.98, 128.07, 125.40, 121.98, 114.21, 95.93, 55.31, 25.39, 25.20,22.08, 21.70. F T–IR (KBr pellet, cm^-1): 3851, 2935, 1652, 1525, 1430, 1248, 1177, 1030, 919.