Preparation of Nitriles

Making nitriles from halogenoalkanes

The halogenoalkane is heated under reflux with a solution of sodium or potassium cyanide in ethanol. The halogen is replaced by a -CN group and a nitrile is produced. Heating under reflux means heating with a condenser placed vertically in the flask to prevent loss of volatile substances from the mixture.

The solvent is important. If water is present you tend to get substitution by -OH instead of -CN.

For example, using 1-bromopropane as a typical halogenoalkane:

We could write the full equation rather than the ionic one, but it slightly obscures what's going on:

The bromine (or other halogen) in the halogenoalkane is simply replaced by a -CN group - hence a substitution reaction. In this example, butanenitrile is formed.

Making a nitrile by this method is a useful way of increasing the length of a carbon chain. Having made the nitrile, the -CN group can easily be modified to make other things - as you will find if you explore the nitriles menu (link a the bottom of the page).

Making nitriles from amides

Nitriles can be made by dehydrating amides. Amides are dehydrated by heating a solid mixture of the amide and phosphorus(V) oxide, P₄O₁₀. Water is removed from the amide group to leave a nitrile group, -CN. The liquid nitrile is collected by simple distillation.

For example, you will get ethanenitrile by dehydrating ethanamide.

Making nitriles from aldehydes and ketones

Aldehydes and ketones undergo an addition reaction with hydrogen cyanide. The hydrogen cyanide adds across the carbon-oxygen double bond in the aldehyde or ketone to produce a hydroxynitrile. Hydroxynitriles used to be known as cyanohydrins.

For example, with ethanal (an aldehyde) you get 2-hydroxypropanenitrile:

With propanone (a ketone) you get 2-hydroxy-2-methylpropanenitrile:

In every example of this kind, the -OH group will be on the number 2 carbon atom - the one next to the -CN group.

The reaction isn't normally done using hydrogen cyanide itself, because this is an extremely poisonous gas. Instead, the aldehyde or ketone is mixed with a solution of sodium or potassium cyanide in water to which a little sulphuric acid has been added. The pH of the solution is adjusted to about 4 - 5, because this gives the fastest reaction. The reaction happens at room temperature.

The solution will contain hydrogen cyanide (from the reaction between the sodium or potassium cyanide and the sulphuric acid), but still contains some free cyanide ions. This is important for the mechanism.

These are useful reactions because they not only increase the number of carbon atoms in a chain, but also introduce another reactive group as well as the -CN group. The -OH group behaves just like the -OH group in any alcohol with a similar structure.

For example, starting from a hydroxynitrile made from an aldehyde, you can quite easily produce relatively complicated molecules like 2-amino acids - the amino acids which are used to construct proteins.

LACTAM

In chemistry, a lactam is a cyclic amide. The name is derived from two chemical terms, lactone, referring to a cyclic ketone; and amide, a compound containing a nitrogen atom next to a carbonyl group. Lactams are named according to the size of the cyclic ring in the lactam: α-lactams, β-lactams, γ-lactams and δ-lactams contain rings made of three, four, five or six atoms, respectively. α-lactams are also called aziridinones. Many widely used antibiotic drugs, including the penicillins and cephalosporins, owe their activity to the presence of a β-lactam structure. The lactams may have substitutions added to the nitrogen atom or any of the non-carbonyl carbon atoms in the base structure. The β-lactam forms the center structure of many antibiotic drugs, such as the cephalosporins and the penicillins.

Beta β, gamma γ and delta δ are the second, third and fourth letters in the alphabetical order of the Greek alphabet, respectively.

Synthesis

General synthetic methods exist for the organic synthesis of lactams.

·      Lactams form by the acid-catalyzed rearrangement of oximes in the Beckmann rearrangement.

·      Lactams form from cyclic ketones and hydrazoic acid in the Schmidt reaction.

·      Lactams form from cyclisation of amino acids.

·      Lactams form from intramolecular attack of linear acyl derivatives from the nucleophilic abstraction reaction.

·      In iodolactamization an iminium ion reacts with an halonium ion formed in situ by reaction of an alkene with iodine.

·      Lactams form by copper catalyzed 1,3-dipolar cycloaddition of alkynes and nitrones in the Kinugasa reaction.

·      Diels-Alder reaction between cyclopentadiene and chlorosulfonyl isocyanate (CSI) can be utilized to obtain both β- as well as γ-lactam. At lower temp (−78 °C) β-lactam is the preferred product. At optimum temperatures, a highly useful γ-lactam known as Vince Lactam is obtained.

Tautomerization to Lactim

Lactim is a cyclic carboximidic acid compound characterized by an endocyclic carbon-nitrogen double bond. It is formed when lactam undergoes tautomerization.

Reactions

Lactams can polymerize to polyamides.