Hofmann-Löffler-Freytag reaction

What is Hofmann-Löffler-Freytag reaction?

The Hofmann-Löffler-Freytag reaction refers to the creation of pyrrolidines or piperidines through the thermal or photochemical breakdown of protonated N-haloamines (in the presence of strong acid such as sulfuric acid H2SO4 or trifluoroacetic acid CF3COOH).

Hofmann-Löffler-Freytag reaction - general reaction scheme - Löffler method - Hofmann-Löffler reaction - Löffler-Hofmann reaction - Löffler-Freytag reaction
Hofmann-Löffler-Freytag reaction

= 3, or 4

Hofmann first reported in 1878 that treating D-1-bromo-2-propylpiperidine with hot sulfuric acid H2SO4 produced a tertiary amine, D-octahydroindolizine. Latter, Löffler and Freytag expanded the reaction to simple secondary amines and found it to be a general method for synthesizing pyrrolidines, exemplified by the conversion of N-bromo-N-methyl-2-butylaminylpyridine to nicotine. The reaction is also referred to as Löffler method, Hofmann-Löffler reaction, Löffler-Hofmann reaction, and Löffler-Freytag reaction.