Some classic aromatic heterocycle syntheses

Our study of heterocyclic compounds is directed primarily to an understanding of their reactivity and importance in biochemistry and medicine. The synthesis of aromatic heterocycles is not, therefore, a main theme, but it is useful to consider just a few examples to underline the application of reactions we have considered in earlier chapters. From the beginning, we should appreciate that the synthesis of substituted heterocycles is probably not best achieved by carrying out substitution reactions on the simple heterocycle. It is often much easier and more convenient to design the synthesis so that the heterocycle already carries the required substituents, or has easily modified functions. We can consider two main approaches for heterocycle synthesis, here using pyridine and pyrrole as targets. 

We can insert the heteroatom into the rest of the carbon skeleton, or attempt to join two units, one of which contains the heteroatom, by means of C-C and C-heteroatom linkages. To make the new bonds, two reaction types are most frequently encountered. Heteroatom-C bond formation is achieved using the heteroatom as a nucleophile to attack an electrophile such as a carbonyl group (see Section 7.7.1). Aldol-type reactions may be exploited for C-C bond formation (see Section 10.3), employing enamines and enols/enolate anions (see Section 10.5). 

We shall now look at some synthetic procedures that merit the descriptor classic because of their general application, and their longevity - some have been around for more than 100 years. Do not worry about remembering the names these commemorate the originators, and we should instead concentrate on the chemistry, which we shall see is usually a combination of processes we have already met. 

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