Reaction of Amines with Alkyl Halides

The reaction of amines with alkyl halides was seen earlier (Section 21.7) as a complicating factor in the preparation of amines by alkylation of ammonia. 

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

A second alkylation may follow, converting the secondary amine to a tertiary amine. Alkylation need not stop there the tertiary amine may itself be alkylated, giving a quaternary ammonium salt. 

Because of its high reactivity toward nucleophilic substitution, methyl iodide is the alkyl halide most often used to prepare quaternary ammonium salts. 

Quaternary ammonium salts, as we have seen, are useful in synthetic organic chemistry as phase-transfer catalysts. In another, more direct application, quaternary ammonium hydroxides are used as substrates in an elimination reaction to form alkenes. 

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The Sn2 reaction of amines with alkyl halides is complicated by a tendency for overalkylation to form a mixture of monoalkylated and polyalkylated products (Section 19-11). Simple primary amines can be synthesized, however, by adding a halide or tosylate (must be a good SN2 substrate) to a large excess of ammonia. Because there is a large excess of ammonia present, the probability that a molecule of the halide will alkylate ammonia is much larger than the probability that it will over-alkylate the amine product. 

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