Reactions of Aliphatic Amines

Simple amines and ammonia are strong nucleophiles and will undergo an S_N2 reaction with alkyl halides (or alkyl groups with "good leaving groups") to give further substitution on the nitrogen, as described previously. They will also react with activated carbonyl compounds to undergo acyl transfer reactions; thus amides are readily formed by the reaction of amines with acid halides, acid anhydrides or carboxylate esters.

The reaction of an amine with a sulfonyl halide forms the sulfonamide. A common reagent utilized in this reaction is p-toluenesulfonyl chloride, producing the corresponding p-toluenesulfonamide.

The base solubility of sulfonamides forms the basis of the Hinsberg test, for distinguishing primary, secondary and tertiary amines; primary p-toluenesulfonamides undergo ionization in strong base to give the base-soluble anion; secondary p-toluenesulfonamides lack the acidic hydrogen and do not form a soluble anion; tertiary amines would yield highly unstable cationic quarternary sulfonamides, and generally do not react at all. Thus, the formation of a base-soluble sulfonamide indicates the presence of a primary amine.

Reaction of primary amines with an excess of iodomethane converts the primary amine into the quarternary ammonium salt. The cationic nitrogen which is now formed is a good leaving group, and will undergo E2 elimination on reaction with Ag₂O to give the alkene, in a reaction known as the Hofmann Elimination.

The Hofmann Elimination is unusual for an E2 elimination because the least substituted alkene is typically formed.

Amides and acid azides can also be converted to amines using the Hofmann and Curtius rearrangements, respectively. Both the amide and acyl azide can be prepared from an intermediate acid halide, and the reaction results in the shortening of the alkyl chain by one carbon (the carbonyl is lost as CO₂).