Nitrile reactions and synthetic routes

​​In a nutshell

Nitriles can undergo a number of reactions to form a different functional group. They can be reduced to produce primary amines and hydrolysed to make carboxylic acids. When synthesising molecules where the product has an extra carbon in relation to the reactant, it is an indication that a new carbon-carbon bond was formed during the synthesis.

Equations

These are general chemical equations. You will need to be able to use these when you write equations for specific substances.

​$$nitrile \ or \ hydroxynitrile \xrightarrow[2. \ dil. \ acid]{1. \ LiAlH_4, \ dry \ ether} primary \ amine \\ \ \\nitrile + hydrogen \xrightarrow[high \ temperature \ and \ pressure]{metal \ catalyst} primary \ amine \\ \ \\nitrile \ + \ hydroxynitrile \xrightarrow[ethanol]{Na} primary \ amine \\ \ \\nitrile \ or \ hydroxynitrile \ + \ water\xrightarrow[reflux]{dil. HCl} carboxylic \ acid$$​​

Aliphatic primary amines

Aliphatic primary amines can be produced by reducing a nitrile or a hydroxynitrile.

$$nitrile \ or \ hydroxynitrile \xrightarrow[2. \ dil. \ acid]{1. \ LiAlH_4, \ dry \ ether} primary \ amine$$​​

Example 

​$$acetonitrile \xrightarrow[2. \ dil. \ acid]{1. \ LiAlH_4, \ dry \ ether} ethylamine \\ \ \\CH_3CN \xrightarrow[2. \ dil. \ acid]{1. \ LiAlH_4, \ dry \ ether}CH_3CH_2NH_2$$​​

However, lithium aluminium hydride is very expensive to use on an industrial scale. Instead, catalytic hydrogenation is used. Nitriles are reduced to primary amines using hydrogen gas, in the presence of a metal catalyst such as nickel or platinum.

​$$nitrile \ +\ hydrogen \xrightarrow[high \ temperature \ and \ pressure]{metal \ catalyst} primary \ amine$$​​

Example 

​$$acetonitrile \ +\ hydrogen \xrightarrow[high \ temperature \ and \ pressure]{cat. \ Ni} ethylamine \\ \ \\CH_3CN \ +\ 2H_2\xrightarrow[high \ temperature \ and \ pressure]{cat. \ Ni}CH_3CH_2NH_2$$

​

Sodium metal in ethanol can also reduce nitriles and hydroxynitriles to primary amines.

$$nitrile \ or \ hydroxynitrile \xrightarrow[ethanol]{Na} primary \ amine$$​​

Example 

$$phenylacetonitrile \xrightarrow[ethanol]{Na} 2-Phenylethylamine \\ \ \\C_6H_5CH_2CN\xrightarrow[ethanol]{Na}C_6H_5CH_2CH_2NH_2$$​​

Note: Phenylacetonitrile is also known as benzyl cyanide.

Carboxylic acids

Nitriles and hydroxynitriles are hydrolysed to a carboxylic acid when they are refluxed with dilute hydrochloric acid.

​$$nitrile \ or \ hydroxynitrile \ + \ water \xrightarrow[reflux]{dil. HCl} carboxylic \ acid$$​​

Nitrile

Hydroxynitrile

Synthetic routes

A reaction where the product has one more carbon atom than the reactant can be due to the reaction synthesis involving a cyanide.

Example 

Suggest how propylamine can be synthesised from bromoethane.

First, draw the molecules to help you visualise what is happening.

You can see that the product is a carbon longer than the reactant. This shows a new carbon-carbon bond was made during the reaction process.

Since a haloalkane is the starting material, it is possible for a cyanide to react with bromoalkane to extend the carbon chain from two to three carbons long. The reaction will proceed via nucleophilic substitution. 

$$bromoethane \ + \ potassium \ cyanide \xrightarrow[reflux]{ethanol}propanenitrile \ + potassium \ bromide$$​​

The nitrile formed can then be reduced to a primary amine using different methods. Here, catalytic hydrogenation will be employed.

$$propanenitrile \ +\ hydrogen \xrightarrow[high \ temperature \ and \ pressure]{cat. \ Ni} propylamine$$​​

Therefore, the overall synthetic route is:

It is very common to use the skeletal formula to represent synthetic routes. You can find below the synthetic route of the example given using the skeletal formula. 

Tip: Use the skeletal formula wherever possible with respect to organic synthesis. It is conventional to do so and it makes it much simpler and easier to identify the parts of the molecule you need to focus on.