Reactivity
Thiophene is considered aromatic, although theoretical calculations suggest that the degree of aromaticity is less than that of benzene. The "electron pairs" on sulfur are significantly delocalized in the pi electron system. As a consequence of its aromaticity, thiophene does not exhibit the properties seen for conventional thioethers. For example the sulfur atom resists alkylation and oxidation. However, oxidation of a thiophene ring is thought to play a crucial role in the metabolic activation of various thiophene-containing drugs, such as tienilic acid and the investigational anticancer drug OSI-930. In these cases oxidation can occur both at sulfur, giving a thiophene S-oxide, as well as at the 2,3-double bond, giving the thiophene 2,3-epoxide, followed by subsequent NIH shift rearrangement.
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