6.07 Ritter-Type Reactions

Abstract

The Ritter reaction is the one-flask reaction of a nitrile and a carbenium ion (or its chemical equivalent) to produce a nitrilium ion, followed by subsequent chemical events. The two principal outcomes are formation of an acyclic amide, or cyclization to yield a wide range of heterocyclic systems. The reaction provides one of the most reliable means of linking a tert alkyl group with a nitrogen atom. In its original form, the carbenium ion was produced from an alkene or alcohol using a strong protic (Brønsted) acid. Nowadays, a very large number of functional groups can be employed, and alternative means are available for obtaining carbenium ions. Important work in developing greener reagents and catalytic processes is described. The acyclic Ritter reaction mechanism involves carbenium ion, nitrilium ion, and imidate intermediates and therefore has a close familial relationship with many other organic reactions. Wagner–Meerwein rearrangements are possible since the Ritter mechanism involves a carbenium ion, and deliberate variation of the reaction conditions can allow the formation of alternative products. Many of its heterocyclic products contain a functional group that can be exploited in further synthesis. Some Ritter-type reactions are highly stereoselective and these provide efficient synthetic routes to complex molecules. This chapter describes and contrasts these various methods, in particular those advances made during the past 25 years.