SN2 reaction of amines with alkyl chlorides to give ammonium salts

by James

Description: Amines will react with alkyl halides to give ammonium salts. Importantly, this occurs even if only one equivalent of the alkyl halide and amine are used.
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Notes: alkylation of amines with alkyl halides is not generally considered to be a useful reaction, because the reaction cannot be stopped after just one addition of alkyl halide. It will continue until the ammonium salt is obtained, and these have limited utility.

Note that X here is halide (Cl, Br, I) or sulfonate (OTs, OMs)

Examples: 

Notes: It’s not possible to “stop” the reaction after reaction with one equivalent of alkyl halide. Again, this is why it’s not generally considered useful since there aren’t many synthetic applications of ammonium salts.

Note that since this is an SN2 reaction and proceeds through backside attack, there will be inversion of configuration at the carbon.

Mechanism: The amine performs an SN2 on the alkyl halide (Step 1, arrows A and B) forming a positively charged nitrogen (“ammonium”). This is deprotonated by a second equivalent of the amine (Step 2, arrows C and D) giving a neutral secondary amine which can now perform a second SN2 on the alkyl halide (Step 3, arrows E and F). This results in a new ammonium salt, which is then deprotonated by a second equivalent of base (Step 4, arrows G and H) giving a tertiary amine, which then performs a third nucleophilic substitution (Step 5, arrows I and J).

Notes: It’s not possible to get this reaction to stop after one alkylation because the tertiary amine (formed after step 4) is a better nucleophile than the secondary amine (formed after step 2) which is a better nucleophile than the primary amine (in step 1).

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{ 2 comments… read them below or add one }

Petr Menzel

Hi, in Description is written “+ salt”. What kind of salt is created? I suppose that there is 2 HX? Thx, P.

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James

The “salt” is the ammonium salts that form during deprotonation of the amine.

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