Reactions of Furans and Benzofurans

There are few general methods for the functionalization of existing furan rings due to their low stability under acidic and aerobic conditions. For this reason, most functionalized furan derivatives are prepared by the cyclization of acyclic precursors using acid, base, or transition metal catalysis. 

Friedel-Crafts reactions, Wittig rearrangements, Michael additions, and intramolecular cyclizations are highlighted below. 

Monobromination of fiiran to produce 2-bromofuran can be accomplished by addition of one equivalent of bromine in DMF in 70% yield. Two equivalents of bromine under the same reaction conditions provides the disubstituted product, 2,5-dibromofuran, in 48% yield. 

Halogenated furans are important intermediates for the synthesis of a number of functionalized furan derivatives through metal-halogen exchange and transition metal-catalyzed cross-coupling reactions, as will be demonstrated throughout this chapter. 

Nitration of furan rings is accomplished by treatment of furan with concentrated nitric acid and sulfuric acid. This protocol was employed by Fathali and co-workers in their concise synthesis of the antibacterial nitrofurazone. Treatment of 2-furaldehyde with nitric acid, followed by treatment with acetic anhydride, gave the corresponding 5-nitrofurfuraldiacetate. Reaction of 5-nitrofurfuraldiacetate with semi- 

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In addition to catalyzing reactions of furans and benzofurans, palladium also plays an important role in a wide variety of reactions that produce the furan and benzofuran ring structures from acyclic and monocyclic starting materials, respectively [1, 148,149], The six major classes of furan and benzofuran precursors are highlighted below. 

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