Five-Membered Rings

      Preparation
Commercial preparation of furan proceeds by way of the aldehyde, furfural, which in turn is generated from pentose containing raw materials like corncobs, as shown in the equation below. Similar preparations of pyrrole and thiophene are depicted in the second row equations. Equation 1 in the third row illustrates a general preparation of substituted furans, pyrroles and thiophenes from 1,4-dicarbonyl compounds, known as the Paal-Knorr synthesis. Many other procedures leading to substituted heterocycles of this kind have been devised. Two of these are shown in reactions 2 and 3. Furan is reduced to tetrahydrofuran by palladium-catalyzed hydrogenation. This cyclic ether is not only a valuable solvent, but it is readily converted to 1,4-dihalobutanes or 4-haloalkylsulfonates, which may be used to prepare pyrrolidine and thiolane.
Dipolar cycloaddition reactions often lead to more complex five-membered heterocycles.

Indole is probably the most important fused ring heterocycle in this class. By clicking on the above diagram three examples of indole synthesis will be displayed. The first proceeds by an electrophilic substitution of a nitrogen-activated benzene ring. The second presumably takes place by formation of a dianionic species in which the ArCH₂(–) unit bonds to the deactivated carbonyl group. Finally, the Fischer indole synthesis is a remarkable sequence of tautomerism, sigmatropic rearrangement, nucleophilic addition, and elimination reactions occurring subsequent to phenylhydrazone formation. This interesting transformation involves the oxidation of two carbon atoms and the reduction of one carbon and both nitrogen atoms.