Five-Membered Heterocyclic Compounds with Two Different Hetero-Atoms in the Ring

This chapter discusses the synthesis, physical and chemical properties of isoxazole and its homologs and derivatives, such as aminoisoxazoles, hydroxyisoxazoles (isoxazolinones, or isoxazolones) and their sulfur analogues, isoxazole carboxylic acids, reduced systems, such as isoxazolines (dihydroisoxazoles), 2-isoxazolines, 4-isoxazolines, isoxazofidines (tetrahydroisoxazoles), and isoxazolidinones. Interest in the derivatives of oxazole was renewed because of their significance in penicillin chemistry. The most familiar example is annnioline, which is obtained from the rye grass Lolium multiflorum. Phenanthroxazoles are synthesized from phenanthrene quinones or better when phenanthrene quinone-imines are heated with primary amines. There are over six hundred patents referring to the application of benzoxazole derivatives as optical brightners and scintillators for cottons and polyesters. Isothiazoles are aromatic in nature, more stable than isoxazoles, and most susceptible to electrophilic attack at C-4. For benzisothiazoles, two structural types are possible depending on which face (c or d) of the heterocycle is fused to the benzene nucleus, benzo[d]isothiazole and benzo[c]isothiazole are more generally known as 1,2-benzisothiazole (or thioindoxazene) and 2,1-benzisothiazole (or thioanthranil), respectively. Selenazoles are the selenium analogues of thiazoles and are prepared in similar ways, although with greater difficulty, a fact accentuated by the toxicity of the necessary intermediates.