Preparing aliphatic amines
Aliphatic amines can be prepared by warming a halogenalkane with ammonia for a few minutes, using aqueous ethanol as a solvent. Ammonia is not only an excellent base, due to the presence of the lone pair of electrons on the molecule but it is also a good nucleophile. The mechanism for this reaction is outlined below:
However this is not the end of the story for this reaction. If you follow the mechanism you can clearly see that
the ammonia simply swaps a hydrogen atom for an ethyl group or
if a different halogenalkane was used, for example bromomethane,
then a methyl group would replace a hydrogen on the ammonia
to form methylamine. The problem is the product of the reaction, the primary amine is a stronger base and a better nucleophile than the ammonia which was the initial starting material. So as the reaction proceeds the concentration of the primary amine produced will increase and it will take over from ammonia as the nucleophile in the reaction mechanism. This will mean that one of the hydrogen atoms on the primary amine will be replaced by an alkyl group to form a secondary amine, this is outlined below using methylamine as the starting primary amine, which ends up forming the secondary amine dimethylamine:
I am sure you can see where this going! The product of the reaction above, the
dimethylamine is a better nucleophile
than the primary amine, methylamine. This means that as the
concentration of the secondary amine, dimethylamine increases
it will take over from the methylamine and form the tertiary amine trimethylamine.
Even here the reaction will not stop! The
trimethylamine will continue to react with the bromomethane and form the quaternary ammonium salt where all
the hydrogen
atoms from the original ammonia molecule
have been replaced by -methyl groups.
This reaction leads to a mixture of products which ultimately reduces the usefulness of this reaction. We can
of course try to stop the
reaction at the first step and only produce the primary amine; methylamine; to do this we
simply try to block the product of the reaction, the methylamine from acting as a nucleophile and undergoing another further reactions by using a large
excess of ammonia. This it is hoped by sheer weight of
numbers the ammonia molecules will
simply block the methylamine and limit the
reaction to produce only the primary amine, methylamine. However if the desired product of the reaction is the quaternary ammonium salt then the reaction mixture needs to be adjusted and a large excess of the halogenalkane is used, this will ensure that there are plenty alkyl groups to substitute for the four hydrogen atoms on the ammonia molecule.
Reduction of nitriles to primary amines
Recall that nitriles contain the functional group R-CN. Nitriles are particularly useful in organic synthesis are they are one of the few ways in which it is possible to extend the carbon chain by 1 carbon atom. Nitriles are also reactive and are easily converted into other useful and reactive molecules including amines. The first two members of the nitriles homologous series are shown below, however you are probably already familar with this homologous series of compounds.
Nitriles can be made by reacting a halogenalkane
with a solution
of potassium or sodium cyanide in ethanol, the reaction is carried out under
reflux. For example the halogenalkane bromoethane
reacts with the cyanide ion (:CN-) to form propanenitrile. The cyanide ion uses its
lone pair of electrons
to attack the δ+ carbon atom in the C-Br bond. The mechanism for this reaction is shown below:
It is the nitrile group (R-CN) that can be reduced to form primary amines. This reduction can be carried in two ways:
- The nitrile group can be reduced using hydrogen in the presence of a nickel or platinum catalyst e.g.
Or
Nitriles and amides can also be reduced to form primary amines using powerful reducing agents such as lithium aluminium hydride (lithium tetrahydridoaluminate, LiAlH4). This acts as a source of hydride ions (H-) which can attack the partially positively charged carbon atom (δ+) in the nitrile group and the polar carbonyl group in the amide. The reaction is carried out in dry ether since LiAlH4 reacts very violently with water. To obtain the amine the product of the reduction reaction is hydrolysed with water. The reaction can be written as shown below, where [H] represents the hydride ions (H-) produced by the lithium aluminium hydride.
Preparation of aromatic or aryl amines
Primary aromatic amines can be produced by the reduction of the nitro group (-NO2) attached to an aromatic ring. The reducing agent used here is a mixture of tin or iron in concentrated hydrochloric acid, this reduction is carried using reflux conditions; as shown below:
Key Points
- Amines can be prepared by the reaction of a halogenalkane with ammonia. however this reaction is not a particularly effective way to produce amines since it tends to produce a mixture of products.
- A more efficient method of preparing primary amines is by the catalytic reduction of a nitrile using a nickel or platinum catalyst and high pressure hydrogen gas.
- Nitriles can also be reduced using LiAlH4, which is a very powerful reducing agent. This will reduce a nitrile to a primary amine.
- Aromatic or aryl amines are usually prepared by the reduction of an aromatic nitro group using a mixture of tin and concentrated hydrochloric acid.