The Beckmann rearrangement which involves the conversion of oximes into amides or lactams in the presence on an acid or acylating agent was discovered in 1886 and is thus one of the oldest reactions in organic synthesis. It remains a widely used method for the introduction of nitrogen into organic molecules.
Mechanistically the reaction is initiated by conversion of the N-hydroxy moiety of the oxime into a suitable leaving group by protonation, Lewis acid coordination or acylation. The activated oxime can isomerize under certain reaction conditions.
MechanismBack to Top
Migration of the substituents with its associated electron pair from carbon to nitrogen with the simultaneous expulsion of the activated hydroxy group results in the generation of a nitrilium species. In some instances, this sequence of events leads to the initil formation of an imidate through the attack of an oxygen nucleophile at the incipient carbocation, which may undergo a Chapman rearrangement to give an N-substituted amide. Alternatively hdrolysis of the nitrilium or imidate species upon workup affords the N-substituted amide product. When cyclic ketoximes are used in the Beckmann rearrangement ring expanded lactams are produced.
The mechanism of Beckmann rearrangement is shown below.
The Beckmann rearrangement normally proceeds with retention of configuration of the migrating group. In general the rearrangement of ketoximes is stereospecific resulting from migration of the substituent anti to the leaving group on nitrogen.
ApplicationBack to Top
An interesting application of the Beckmann rearrangement is in the formation of heterocyclic rings, for example, when cyclopentanonoxime is subjected to the Beckmann rearrangement, the nitrogen atom enters the ring to form 2-piperidone.
On the other hand Hill have shown that the oximes of some spiro-ketones abnormal Beckmann rearrangements in the presence of polyphosphoric acid. Although aliphatic ketoximes are not known in two isomeric forms some may produce two products when subjected to the Beckmann rearrangement.