(E)-Benzaldehyde O-{[3-(pyridin-3-yl)isoxazol-5-yl]meth­yl}oxime

Rodolfo Moreno-Fuquen; Alix Elena Loaiza; John Diaz-Velandia; Alan R Kennedy; Catriona A Morrison

doi:10.1107/S1600536812010732

. 2012 Mar 17;68(Pt 4):o1080. doi: 10.1107/S1600536812010732

(E)-Benzaldehyde O-{[3-(pyridin-3-yl)isoxazol-5-yl]methyl}oxime

Rodolfo Moreno-Fuquen ^a,^*, Alix Elena Loaiza ^b, John Diaz-Velandia ^b, Alan R Kennedy ^c, Catriona A Morrison ^c

PMCID: PMC3344035 PMID: 22589944

Abstract

The asymmetric unit of the title compound, C₁₆H₁₃N₃O₂, contains two independent molecules in which the pyridine and benzene rings form dihedral angles of 81.7 (2) and 79.8 (2)°, indicating the twist in the molecules. In the crystal, weak C—H⋯N interactions link molecules into chains along [100].

Related literature

For organic synthesis of isoxazole systems, see: Giomi et al. (2008 ▶); Chukanov & Reznikov (2011 ▶). For the biological activity of isoxazole systems, see: Meyers et al. (2011 ▶); Basappa et al. (2003 ▶); Lee et al. (2009 ▶); Talley et al. (2000 ▶); Farrerons et al. (2003 ▶); Edgard et al. (2004 ▶); For hydrogen-bond graph-set motifs, see: Etter (1990 ▶). For hydrogen bonding, see: Nardelli (1995 ▶).

Experimental

Crystal data

C₁₆H₁₃N₃O₂
M _r = 279.29
Orthorhombic,
a = 19.364 (12) Å
b = 4.459 (3) Å
c = 31.775 (19) Å
V = 2744 (3) Å³
Z = 8
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 100 K
0.40 × 0.01 × 0.01 mm

Data collection

Rigaku Saturn724+ diffractometer
17573 measured reflections
4762 independent reflections
3544 reflections with I > 2σ(I)
R _int = 0.086

Refinement

R[F ² > 2σ(F ²)] = 0.059
wR(F ²) = 0.136
S = 0.99
4762 reflections
379 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: CrystalClear-SM Expert (Rigaku, 2011 ▶); cell refinement: CrystalClear-SM Expert; data reduction: CrystalClear-SM Expert; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶) and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812010732/vm2159sup1.cif

e-68-o1080-sup1.cif^{(25.3KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812010732/vm2159Isup2.hkl

e-68-o1080-Isup2.hkl^{(233.3KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812010732/vm2159Isup3.cml

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
C26—H26⋯N3ⁱ	0.95	2.43	3.374 (5)	174
C10—H10⋯N6ⁱⁱ	0.95	2.49	3.443 (5)	179

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

Acknowledgments

RMF is grateful to the Spanish Research Council (CSIC) for the use of a free-of-charge licence to the Cambridge Structural Database (Allen, 2002 ▶). RMF also thanks the Universidad del Valle, Colombia, and AEL thanks Universidad Javeriana, Colombia, for partial financial support. Thanks are due to the National Crystallography Service at the University of Southampton for the data collection.

supplementary crystallographic information

Comment

The isoxazoles are five-membered heterocyclic systems with one oxygen atom and one nitrogen atom at adjacent positions. These compounds are used as intermediates in organic synthesis due to their easy transformation into important groups such as enamino ketones, enoximes, 1,3-dicarbonyl compounds, γ-amino alcohols, and β-hydroxy nitriles (Giomi et al., 2008; Chukanov & Reznikov, 2011).

They also have been widely used in the synthesis of nucleosides, alkaloids and other natural compounds. Many derivatives exhibit interesting applications in various fields such as agriculture, industry, and medicine. The wide spectrum of biological activities characteristic of these systems, comprises analgesic (Meyers et al., 2011), antifungal (Basappa et al., 2003), antiviral (Lee et al., 2009), anti-inflammatory (Talley et al., 2000), and antiobesity (Giomi et al., 2008) activities.

In our research group, we are interested in the synthesis of nitrogen containing compounds with potential biological activity such as isoxazoles and oximes. The (E)-benzaldehyde O-(3-(pyridin-3-yl)isoxazol-5-yl)methyl oxime, (I), is an isoxazole analogue exhibiting important antibiotic (Farrerons et al., 2003) and immunomodulator properties (Edgard et al., 2004). On the other hand, the oxime function is an important pharmacophore group present in a wide variety of biologically active compounds, such as 3-oxiconazole and cefuroxime. Compound I was synthesized via 1,3-dipolar cycloaddition of an alkyne and a nitrile oxide obtained by treatment of (E)-nicotinaldehyde oxime with NaOCl. The reaction proceeded with high regioselectivity affording only the 5-substituted isomer in 45% yield. The molecular structure of I is shown in Fig. 1. The asymmetric unit of (I) contains two independent molecules (1) and (2). In both molecules, the isoxazole and pyridine rings are almost coplanar (r.m.s. deviation of all non-hydrogen atoms = 0.0044 Å). The dihedral angles between the mean planes defined by isoxazole and pyridine rings are 3.0 (3)° in molecule 1 and 5.8 (3)° in molecule 2. The pyridine and benzene rings form a dihedral angle of 81.7 (2)° in molecule 1 and 79.8 (2)° in molecule 2 indicating the twist in the molecules. The torsion angles of C8—O1—N1—C1 in (1) and C24—O3—N4—C17 in (2) are 176.2 (3) and -173.8 (3)° respectively and the least-squares fit of C2 C1 N1 O1 C8 C9 plane in (1) and C18 C17 N4 O3 C24 C25 plane in (2) show a r.m.s deviation of fitted atoms of 0.2117 and 0.2090 Å respectively, indicating the similar conformation of both molecules. The crystal packing is stabilized by weak C—H···N interactions (see Table 1, Nardelli, 1995). The molecules 1 and 2, are intertwined forming C(6) (Etter, 1990) chains of molecules along [100], see Fig. 2.

Experimental

A stirred solution of (E)-benzaldehyde O-prop-2-ynyl oxime (318 mg, 2 mmol) and (E)- nicotinaldehyde oxime (122 mg, 1 mmol) in dichloromethane (4 ml) was placed on an ice bath during 5 minutes and then NaOCl in aqueous solution 5.25% (3 ml, 2.5 mmol) was added. The mixture was allowed to react for 30 minutes. After this period the phases were separated and the aqueous phase was extracted with AcOEt. The combined organic phases were dried with anhydrous Na₂SO₄, filtered and concentrated under low pressure. Purification of the crude mixture by flash column chromatography with 25% (v/v) AcOEt/hexane yielded a white solid (126 mg, 45% yield, mp 322 (1) K).

(E)-benzaldehyde O-(3-(pyridin-3-yl)isoxazol-5-yl)methyl oxime ¹H NMR (300 MHz) δ, 9.04 (d, 1H), 8.70 (dd, 1H), 8.20 (ddd, 1H), 8.19 (s, 1H), 7.63–7.60 (m, 2H), 7.46–7.38 (m, 4H), 6.69 (t, 1H), 5.34 (d, 2H). ¹³C-NMR δ, 170.25, 159.10, 150.75, 150.45, 147.74, 134.31, 131.45, 130.37, 128.78, 127.30, 123.86, 101.24, 66.66. MS—EI M⁺ 279.1, 159.1 (100%).