Aminolysis

Aminolysis (/am·i·nol·y·sis/ amino meaning "contains NH₂ group", and lysis meaning "to unbind") is any chemical compound reacts with a molecule of ammonia or an amine and causes a molecule to split into two parts, containing the addition of (or substitution by) an amino group —NH—. The subset of aminolysis reactions involving ammonia is known as ammonolysis.^α

Reaction

Alkyl Group

An example of an aminolysis reaction is the replacement of a halogen in an alkyl group (R-X) by an amine (R'-NH₂) and the elimination of hydrogen halide (HX).

R-X + R'-NH₂ → R-NH-R' + HX

Synthesis of Peptide

Another common example is the reaction of a primary amine or secondary amine with a carboxylic acid or with a carboxylic acid derivative to form an amide. This reaction is widely used, especially in the synthesis of peptides. On the simple addition of an amine to a carboxylic acid, a salt of the organic acid and base is obtained. To overcome this, the carboxylic acid first needs to be "activated". This is usually done by converting the acid into a more reactive derivative (i.e. anhydride, acid halide) or by using a coupling agent. In some cases, high temperatures (>200 °C) can overcome salt formation by driving off water, without the need for "activation" of the carboxyl group. The downside to this simple reaction is that the compounds may decompose at these elevated temperatures.

The carboxylic acid derivatives can be esters, anhydrides, acid halides or any other activated species.

The choice of activated carboxyl group or coupling agent can be very important in peptide synthesis, as using the wrong one can lead to racemization.

Making amides from a carboxylic acid

Making an amide is one of the processes which require ammonia as a reactant. There are other processes of preparing an amide such as from acid anhydrides and acyl chloride.

Carboxylic acid reacts with ammonia carbonate, to convert carboxylic acid to ammonium salt. In this case, we use ethanoic acid (excess) with solid ammonia carbonate, producing ammonium salt which is ammonium ethanoate (acetate), also water and carbon dioxide. The ammonia carbonate needs to be added slowly, and wait till the reaction is complete (all carbon dioxide is released).

2 CH₃COOH + (NH₄)₂CO₃ → 2 CH₃COONH₄ + H₂O + CO₂

After the reaction is completed ammonium acetate is heated under reflux (170 °C) to dehydrate the salt and eliminate excess acetic acid and water, so the remaining is acetamide

CH₃COONH₄ → CH₃CONH₂ + H₂O

Acetic acid needs to be in excess because it can prevent ammonium salt to split into ammonia and parent acid when it gets heating. Although cooling is the reverse reaction of heating, ammonium salt cannot recombine as ammonia can vapor out of the mixture.

Notes

^α For additional details, see Solvolysis#Ammonolysis.