Reactivity of Five-membered Rings with Two or More Heteroatoms

Reactivity of Five-membered Rings with Two or More Heteroatoms 

In this initial section the reactivities of the major types of azole aromatic rings are briefly considered in comparison with those which would be expected on the basis of electronic theory, and the reactions of these heteroaromatic systems are compared among themselves and with similar reactions of aliphatic and benzenoid compounds. Later in this chapter all these reactions are reconsidered in more detail. It is postulated that the reactions of azoles can only be rationalized and understood with reference to the complex tautomeric and acid-base equilibria shown by these systems. Tautomeric equilibria are discussed in Chapter 2.4. Acid-base equilibria are considered in Section 3.4.1.3 of the present chapter. 

Replacing a CH group of benzene with a nitrogen atom gives pyridine (1) replacing a CH = CH group of benzene with NH, O or S gives pyrrole, furan or thiophene (3), respectively. 

The carbon atoms of azole rings can be attacked by nucleophilic (Section 3.4.1.6), electrophilic (Section 3.4.1.4) and free radical reagents (Section 3.4.1.9.2). Some system, for example the thiazole, imidazole and pyrazole nuclei, show a high degree of aromatic character and usually revert to type if the aromatic sextet is involved in a reaction. Others such as the isoxazole and oxazole nuclei are less aromatic, and hence more prone to addition reactions. 

Electron donation from pyrrole-like nitrogen, or to a lesser extent from analogous sulfur or oxygen atoms, helps electrophilic attack at azole carbon atoms, but as the number of heteroatoms in the ring increases, the tendency toward electrophilic attack at both C and N decreases rapidly. 

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Reactivity of Five-membered Rings with Two or More Heteroatoms 4.02.1.2.2 Photochemical fragmentation... 

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