Lander rearrangement

What is Lander rearrangement?

The Lander rearrangement, which is a thermal conversion of alkyl imidates (also called imino ethers) into N-alkyl amides, was initially reported by Wheeler and Johnson in 1899. Subsequently, Lander extensively explored this reaction from 1900 onwards. This reaction occurs in the presence of an alkylating agent and is named after Lander.

Lander rearrangement - general reaction scheme
Lander rearrangement
  • R1, R2 = alkyl, aryl
  • R3 = alkyl

During this 1,3-shift process, when the alkylating agent’s alkyl group differs from that of the substrate, mixed alkyl amides are produced. However, when a lower alkyl group’s alkylating agent is used for the pyrolysis of alkyl imidates, the N-alkyl amides are more likely to form, with the lower alkyl group substituting the alkyl groups. As early as 1897, this trend of alkyl group substitution was postulated for the conversion of 2-methoxyquinoline or 2-ethoxyquinoline into N-methyl-2-quinolone with an excess of methyl iodide.

It should be noted that this rearrangement also occurs smoothly in the absence of an alkylating agent, as demonstrated by the transformation of N-substituted imidates to N,N-disubstituted amides during distillation in vacuo. This reaction is now referred to as the Chapman rearrangement.

A common application of Lander rearrangement is the conversion of methoxypyridines to N-methylpyridones.