Sulfuric acid reaction with haloamines

A common feature of the reactions in this section is that they serve to introduce functionality at a position remote from functional groups already present. As such, they have proved very useful in synthesizing many compounds, especially in the steroid field (see also 19-2 and 19-14). When N-haloamines in which one alkyl group has a hydrogen in the 4 or 5 position are heated with sulfuric acid, pyrrolidines or piperidines are formed, in a reaction known as the Hofmann-Loffier reaction... 

Heating or photolytic treatment of A,A-dialkyl-A-haloamine in sulfuric acid or trifluoroacetic acid, followed by neutralization with a base, generates a pyrrolidine or piperidine skeleton. This is the Hofmann-Loffler-Frey tag reaction, and the reaction comprises of the formation of an electrophilic aminium radical, 1,5-H shift (6-membered transition state) or 1,6-H shift (7-membered transition state), formation of 4-haloalkyl ammonium or 5-haloalkyl ammonium, and its polar cyclization by neutralization with a base. Eq. 6.16 shows the formation of A-alkyl pyrrolidine (31) from A-chloro-A-alkyl-A-butylamine (30) in sulfuric acid [46, 47]. 

Rearrangements in the Displacement Reactions of 0-Hydroxy and 0-Haloamines or Sulfides. When displacement reactions are carried out with 0-hydroxy and 0-haloamines or sulfides, the product formed often is found to have the nitrogen or sulfur atom attached to the carbon atom where substitution would have been expected. The new substituent becomes affixed to the carbon atom which originally held the nitrogen or sulfur atom. Thus when the glycol XXVIII was treated with hydrochloric acid, the dichloride XXIX was obtained.29 It is... 

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