Carbon-carbon Bond Formation

This lesson covers: 

1. How nitriles are formed from haloalkanes and carbonyl compounds
2. The mechanisms for nitrile formation
3. The reduction and hydrolysis reactions of nitriles
4. Alkylation and acylation reactions with benzene rings

Nitriles contain a C≡N functional group

Organic nitriles contain the nitrile functional group, C≡N.

Nitriles are useful intermediates in organic synthesis because:

• They can be easily converted into other functional groups like amines and carboxylic acids through reduction and hydrolysis.
• Reactions that form nitriles create new carbon–carbon bonds. Forming C-C bonds is vitally important in organic chemistry as it allows the synthesis of new compounds with longer carbon chains.

Some key organic synthesis reactions involving nitriles are discussed below.

Forming nitriles from halogenoalkanes

Nitriles can be synthesised through a nucleophilic substitution reaction between a halogenoalkane and a cyanide salt, like potassium cyanide (KCN), in ethanol. This reaction extends the carbon chain by 1 atom.

For example, bromoethane which contains 2 carbon atoms can be converted into propanenitrile which contains 3 carbon atoms:

CH₃CH₂Br + KCN ➔ CH₃CH₂CN + KBr

Mechanism of nitrile formation

The formation of nitriles from halogenoalkanes, such as bromoethane, involves a nucleophilic substitution mechanism:

1. The cyanide ion (CN^-) acts as a nucleophile, attacking the carbon atom that is partially positive due to its attachment to electronegative bromine atom.
2. This action breaks the carbon-bromine bond, substituting the halogen with a nitrile group and displacing a bromide ion.

Forming hydroxynitriles from carbonyl compounds

Aldehydes and ketones can react when heated with hydrogen cyanide (HCN) in a nucleophilic addition reaction to form a product known as a hydroxynitrile. This reaction also increases the carbon chain length.

For example, ethanal which contains 2 carbon atoms can be converted into 2-hydroxypropanenitrile which contains 3 carbon atoms:

CH₃CHO + HCN ➔ CH₃CH(OH)CN

Hydrogen cyanide is very hazardous to use directly, so it is often generated in situ by mixing sodium cyanide with sulfuric acid.

Mechanism of hydroxynitrile formation

The formation of hydroxynitriles from carbonyl compounds, such as ethanal, follows a nucleophilic addition mechanism:

1. The cyanide ion (CN^-), acting as a nucleophile, attacks the partially positive carbon atom.
2. A bond between carbon and cyanide forms, and an OH group is added.
3. An H⁺ ion is lost, resulting in the hydroxynitrile product.

Nitriles are useful synthetic intermediates

Nitriles can be easily transformed into two other key functional groups: amines and carboxylic acids.

Reducing nitriles to primary amines

Catalytic hydrogenation of nitriles yields primary amines. This involves reacting the nitrile with hydrogen gas (H₂) using a nickel catalyst.

For example, propanenitrile is reduced to propylamine:

CH₃CH₂C≡N + 2H₂ ➔ CH₃CH₂CH₂NH₂

Here, the nitrile triple bond is reduced to a single N-H bond.

Hydrolysing nitriles to carboxylic acids

Hydrolysis of nitriles by heating with dilute aqueous acid converts the nitrile into a carboxylic acid through a nucleophilic addition-elimination mechanism.

For example, propanenitrile is hydrolysed to propanoic acid:

CH₃CH₂C≡N + 2H₂O + HCl ➔ CH₃CH₂COOH + NH₄Cl

Water molecules act as the nucleophile, adding across the triple bond. Ammonium chloride is a by-product, and a carboxyl group is introduced.

Forming carbon-carbon bonds with benzene

Alkylation and acylation reactions can introduce alkyl and acyl side chains onto a benzene ring, respectively.

Alkylation of benzene

Alkylation involves adding an alkyl group to a benzene ring using a halogenoalkane and a Friedel-Crafts catalyst, such as aluminium chloride (AlCl₃).

For example, the ethylation of benzene using chloroethane is:

The products of alkylbenzene are valuable chemical feedstocks and provide substituents for further reactions on the benzene ring.

Acylation of benzene

Acylation introduces an acyl group (RCO^-) onto a benzene ring using an acyl chloride and a Friedel-Crafts catalyst like aluminium chloride (AlCl₃).

This process converts benzene into a ketone, adding an additional reactive functional group for further reactions.

For example, the acylation of benzene using ethanoyl chloride is: