Loffler ring closure

Coleman and Goheen409 found it better to use iV-chloro amines rather than the A-bromo compounds for synthesis of pyrrolidines and in this way achieved yields of around 75% of substituted pyrrolidines. The method has also proved valuable for synthesis of bicyclic tertiary amines.410"412 Schmitz413 applied it to N,N-dibromo derivatives of primary amines from iV,JV-dibromo-l-propylbutylamine he obtained pyrrolizidine in 35% yield,414 the best yields being obtained here, as in other cases,412 415 416 when the reaction is carried out with irradiation in ultraviolet light. Recently ring closure was also achieved with JV-monochloro derivatives of primary amines 417 pyrrolidine (70%) was obtained from butylamine, 2-methylpyrrolidine (80%) from pentylamine, and 2-propylpyrrolidine (50% and 70%, respectively) from heptylamine or 1-pro-pylbutylamine.417 The mechanism of the Hofmann-Loffler reaction has been discussed by Wawzonek and Culbertson.416... 

Sulfuric acid/irradiation Loffler-Freytag ring closure... 

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

Dialkylamino groups may, in principle, be introduced into aromatic rings using the dialkylchloroamine and concentrated sulphuric acid , except in those cases where the chloroamine undergoes preferential ring closure (Hofmann-Loffler reaction ) (reaction 3). However,... 

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