Free-Radical Reactivity of Thiazoles

The free-radical reactivity of thiazoles has been well studied with various radicals such as methyl, phenyl, substituted phenyl, cyclohexyl, and aromatic-heterocyclic, in nonpolar solvent or strong acids (180-182). 

---

Free-radical reactivity of thiazole has been calculated by semiempirical methods, and results free valence and localization energy) have been compared with experimental data. For mono- and dimethylthiazoles the radical localization energy of the unsubstituted position may be correlated with the logarithm of experimental reactivity (180, 200). The value of the slope shows that a Wheland-type complex is involved in the transition state. 

No systematic study of the free radical reactivity of aminothiazole derivatives has yet been reported. Their behavior, however, may be extrapolated from the detailed work performed on other thiazoles (see Chapter III. Section IX. 1). 

The free radical arylation of thiazole (391) has been performed either by the Gomberg-Bachmann (392) decomposition of aryldiazonium chlorides (119,393), by the thermal decomposition of benzoyl peroxide (394-397) or N-nitrosoacetanilide (398), or by the photolysis of benzoyl peroxide or iodobenzene (398). The three monophenylthiazoles are obtained in the practically constant proportions 2-phenyl, 60% 5-phenyl, 30% 4-phenyl, 10%, giving the order, 2>5>4, of decreasing reactivity of the three positions of thiazole toward phenyl radicals (398). Competition reactions with nitrobenzene (397) gave an estimation of the globed reactivity of thiazole relative to benzene of 0.75 with the partial rate factors f2 = 2.2, /s=1.9, /4 = 0.5. When the thermolysis of benzoyl peroxide is performed in acetic acid solution, the substrate in reaction is the conjugate acid of thiazole the global reactivity is enhanced to 1.25,... 

---