Halides, alkyl, reaction with amines

Nucleophilic substitution results when primary alkyl halides are treated with amines. The reaction of amines with... 

This is clearly a much longer sequence to make a primary amine than simple reaction with ammonia. It does not suffer from problems of polyalkylation, however, and the yield of the amine for the two-step sequence is often higher than the direct reaction with an amine. The fact that this procedime is used more often to make aliphatic primary amines than the reaction of ammonia with an alkyl halide suggests the severity of the problems associated with polyalkylation. The preparation of secondary or tertiary amines often requires the use of the S- 2 reaction with amines, however. Other amine surrogates are known, including the azide ion (Section 11.3.4) and the cyanide ion (Section 11.3.5), but both give primary amines as the end product. 

Amines are powerful nucleophiles which react under neutral or slightly basic conditions with several electron-accepting carbon reagents. The reaction of alkyl halides with amines is useful for the preparation of tertiary amines or quaternary ammonium salts. The conversion of primary amines into secondary amines is usually not feasible since the secondary amine tends towards further alkylation. 

The reaction of amines with alkyl halides was seen earlier (Section 22 7) as a complicat ing factor in the preparation of amines by alkylation of ammonia... 

Various sources of fluoride ion have been investigated, of which highly nucleophilic tetraalkylammonium fluorides ate the most effective Thuf, fluoro alkyl halides and N (fluoroalkyl)amines are efficiently synthesized by treatment of the corresponding trifluoromethanesulfonic esters with tetrabutylammonium fluoride trihydrate in aprotic solvents [5fl] (equation 34) The displacement reactions proceed quantitatively at room temperature within seconds, but tail with hydrogen fluoride-pyridine and give reasonable yields only with hydrogen fluo ride-alkylamine reagents... 

The reaction of potassium phthalimide 1 with an alkyl halide 2 leads to formation of a N-alkyl phthalimide 3/ which can be cleaved hydrolytically or by reaction with hydrazine (Ing-Manske variant) to yield a primary amine 5. This route owes its importance as a synthetic method to the fact that primary amines are prepared selectively, not contaminated with secondary or tertiary amines. 

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