chapter  21
52 Pages

The synthesis of five- and six-membered heterocyclic compounds

BySir Richard Norman, J.M. Coxon

Heterocyclic systems are of widespread occurrence in nature, particularly in such natural products as nucleic acids, plant alkaloids, anthocyanins and flavones, and the haem pigments and chlorophyll. In general, a reaction that forms a strainless or near-strainless five- or six-membered ring occurs readily than the corresponding intermolecular reaction because the entropy of activation is much more favourable. The indole system occurs in the essential α-amino acid tryptophan, in the plant alkaloids which owe their biogenetic origin to tryptophan, and in indigo and Tyrian purple, two dyestuffs obtained from natural sources. Of the many methods of synthesis which have been developed, six are of particular importance. The six methods are the Fischer synthesis, the Madelung synthesis, the Bischler synthesis, the Gassman synthesis, and the Nenitzescu synthesis. Systems with two heteroatoms are usually constructed from two compounds of which one contains both heteroatoms as nucleophiles and the other contains two electrophilic groups.