isoxazole

Isoxazole is a five-membered heteroaromatic ring containing adjacent nitrogen and oxygen atoms, corresponding to the 1,2-oxazole framework. The ring comprises three carbon atoms and two heteroatoms arranged in a planar, aromatic system with six π electrons. The unsubstituted molecule has the formula C3H3NO, and most practical isoxazole compounds bear various substituents at the carbon positions.

Isoxazoles are polar and typically exhibit relatively weak basicity at the ring nitrogen due to aromatic stabilization. They are chemically stable under many conditions, but electrophilic substitution and other ring transformations can occur at the carbon atoms, depending on substituents. The ring can participate in hydrogen bonding and often shows moderate lipophilicity, modulated by substituents.

Synthesis: Isoxazoles can be prepared by several routes. Common methods include cyclocondensation of hydroxylamine derivatives with β-dicarbonyl compounds, and 1,3-dipolar cycloaddition of nitrile oxides to alkynes followed by oxidation to the aromatic ring.

Applications and occurrence: Isoxazole rings occur in numerous natural products and pharmaceuticals, where they serve as bioisosteres or pharmacophores that influence potency and metabolic stability. Substituted isoxazoles are found in antifungal, anti-inflammatory, antibacterial, and anticancer agents, among other applications. The isoxazole scaffold is valued in medicinal chemistry for its polarity, planarity, and ability to engage in hydrogen bonding.