1-(3-p-Tolyl­isoxazol-5-yl)cyclo­hexa­nol

Ouafaa Khalil; Khalid Bougrin; Rachid Benhida; Mohamed Soufiaoui; Lahcen El Ammari

doi:10.1107/S1600536809044900

. 2009 Nov 4;65(Pt 12):o2971. doi: 10.1107/S1600536809044900

1-(3-p-Tolylisoxazol-5-yl)cyclohexanol

Ouafaa Khalil ^a, Khalid Bougrin ^a, Rachid Benhida ^b, Mohamed Soufiaoui ^a, Lahcen El Ammari ^c,^*

PMCID: PMC2972041 PMID: 21578712

Abstract

The title compound, C₁₆H₁₉NO₂, contains two molecules in the asymmetric unit. Each molecule is composed of three interconnected rings, two essentially planar rings, viz. the isoxazole and the methylbenzyl aromatic ring [maximum deviations of 0.0027 (13) and 0.0031 (19) Å from the isoxazole and methylbenzyl ring planes, respectively, in the first molecule, 0.0018 (12) and 0.019 (2) Å in the second molecule], and one cyclohexanol ring having a chair conformation. Although the two molecules have similar bond distances and angles, they differ in the orientation of the cyclohexanol ring with respect to the tolylisoxazole unit. In the first molecule, the dihedral angle between the isoxazole and methylbenzyl rings is 22.03 (8)° and between the isoxazole and cyclohexanol rings is 30.15 (8)°. The corresponding values in the second molecule are 6.13 (10) and 88.44 (8)°, respectively. In the crystal, the molecules are linked by O—H⋯O and O—H⋯N hydrogen bonds, building up a zigzag chain parallel to the a axis.

Related literature

For isoxazole derivatives as building blocks in organic synthesis and combinatorial chemistry, see: Tu et al. (2009 ▶); Tang et al. (2009 ▶). For their biological activity, see: Deng et al. (2009 ▶); Kozikowski et al. (2008 ▶); Lee et al. (2009 ▶). graphic file with name e-65-o2971-scheme1.jpg

Experimental

Crystal data

C₁₆H₁₉NO₂
M _r = 257.32
Orthorhombic,
a = 10.9404 (3) Å
b = 9.7136 (3) Å
c = 26.9207 (7) Å
V = 2860.88 (14) Å³
Z = 8
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 298 K
0.18 × 0.17 × 0.10 mm

Data collection

Bruker X8 APEXII diffractometer
Absorption correction: none
87116 measured reflections
4377 independent reflections
3820 reflections with I > 2σ(I)
R _int = 0.032

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.105
S = 1.04
4377 reflections
347 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXS97 (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 I, global. DOI: 10.1107/S1600536809044900/dn2504sup1.cif

e-65-o2971-sup1.cif^{(23.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809044900/dn2504Isup2.hkl

e-65-o2971-Isup2.hkl^{(411.2KB, 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
O1—H1⋯O2	0.82	1.98	2.7892 (12)	168
O2—H2⋯N2ⁱ	0.82	2.05	2.8629 (16)	173

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for making this work possible. They also thank H. Zouihri for his helpful technical assistance during the X-ray measurements.

supplementary crystallographic information

Comment

Isoxazole derivatives are important class of heterocyclic compounds and their chemical and biochemical properties have been extensively studied. They have served as a versatile building blocks in organic synthesis and combinatorial chemistry (Tu et al. 2009, Tang et al. 2009). Isoxazole systems have also been targeted in synthetic investigations for their known biological and pharmacological properties such as hypoglycemic, anti-inflammatory and anti-bacterial activities. Recently, the growing interest in such analogues also rises from their high potential value as antiviral (Deng et al. 2009, Lee et al. 2009) and anti-tumor agents (Kozikowski et al. 2008).

We have undertaken the X-ray diffraction study of the title compound, in order to understand the molecular features which stabilize its observed conformation. The asymmetric unit contains two molecules crystallographically independent. Each molecule is formed by three interconnected cycles, two essentially planar rings: isoxazole and methylbenzyl rings while the 3rd ring (cyclohexanol) has a chair conformation (Fig. 1). The difference between the molecules lies in the orientation of the rings in each molecule as shown in the fitting drawing (Fig. 2) obtained with PLATON (Spek, 2003). Thus in the first molecule (C1 to C15) the dihedral angles between the isoxazole ring and methylbenzyl ring planes is 22.03 (8)° and between the isoxazole and cyclohexanol ring planes is 30.15 (8)°. Whereas in the second molecule (C16 to C30), equivalent angles have as values 6.13 (10) and 88.44 (8)°, respectively.

The two molecules within the asymmetric unit are linked through O-H···O hydrogen bond building a pseudo dimer. These pseudo dimers are further linked to each other by O-H···N hydrogen bonds forming a zig-zag like chain parallel to the a axis (Table 1, Fig. 3).

Experimental

A mixture of 1-ethynylcyclohexanol (1 mmol) and p-methylbenzylaldoxime (1.2 mmol) was dissolved in CH₂Cl₂ (20 ml), the solution was then cooled thoroughly with ice at 0–5°C. 15 ml of sodium hydroxide solution (12 g. of sodium hydroxide per 100 g. of water) were gradually added under vigorously stirring for 5 h. The organic phase was separated and dried over anhydrous sodium sulfate, filtered and the solvent evaporated under reduced pressure. The residue was purified by recrystallization from ethanol. The structure of adduct was confirmed by spectroscopic methods.