Freytag s. Loffler

In 1878, Hofmann reported that treatment of D-l-bromo-2-propylpiperidine (3) with hot sulfuric acid gave rise to a tertiary amine 4, D-octahydroindolizine. In the ensuing decade, Loffler and Freytag extended the reaction to simple secondary amines and found it to be a general way to synthesize pyrrolidines as exemplified by transformation of N-bromo-A-methyl-2-butylaminylpyridine 5 to nicotine (6). The Hofmann-Loffler-Freytag reaction is sometimes referred to as Loffler s method, Hofmann-Loffler reaction, Loffler-Hofmann reaction, as well as Loffler-Freytag reaction. 

Loffler-Freytag pyrrolidine ring closure, with prim, amines, s. 17, 565... 

As already described in Section IV,B, the A-chloro derivatives of the 16-unsubstituted(22i2 25(8)-and (22 S 25iJ)-22,26-epimino-5a-cholestan-3 -ols smoothly afford the corresponding solanidanes by photochemically induced Hofmann-Loffler-Freytag cyclization employing similar re-... 

Hammerum, S. (1981) Rearrangement and hydrogen abstraction reactions of amine cation radicals A gas-phase analogy to the Hofmann-Loffler-Freytag reaction. Tetrahedron Letters, 21,157-160. 

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