288-14-2 / Isoxazole

Isoxazoles belong to an important class of five-membered aromatic heterocycles containing two electronegative heteroatoms, nitrogen and oxygen, in a 1,2-relationship and three regular sp2 carbon atoms. These molecules are found to be key components in various synthetic products in daily use and also present as a pharmacophore essential for biological activity in many drugs and bioactive natural products. In addition, isoxazoles have demonstrated their ability to exhibit hydrogen bond donor/acceptor interactions with a variety of enzymes and receptors. Synthetically, isoxazoles serve as valuable precursors for the construction of diverse molecules, including many natural products. In a recent example, an appropriately substituted isoxazole ring system was employed as a 1,3-dicarbonyl equivalent in enantioselective synthesis of tetracycline antibiotics.

Physical Properties

Isoxazole is a colorless liquid with a bp of 94.5°C, soluble in organic solvents and with a pyridine-like odor. It is a very weak base with a pKa of 1.3 and is less aromatic than the rest of the five-membered heterocycles. Its dipole moment in benzene is 3.3 D.

Chemical Reactivity

It is a π-excessive heterocycle and possesses typical properties of furan and pyridine. With the electron-attracting property of the pyridine type of nitrogen and the electron-donating feature of oxygen, electrophilic substitution occurs more readily than pyridine. Isoxazoles can be functionalized to generate various complex structures. Isoxazole is an aromatic system and its aromaticity is highly influenced due to the presence of O and N heteroatoms in the five-membered ring. This heteroaromatic system undergoes various reactions such as electrophilic substitution, nucleophilic substitution, oxidation, reduction, etc.