Carboxylic acids and derivatives - AL only (3.3.9)

Carboxylic acids are weak acids and are able to donate protons to bases, such as metal oxides and hydroxides to form carboxylate salts and water in neutralisation reactions. These are analogous to the reactions of strong mineral acids.

The reaction of carboxylic acids with carbonates or hydrogen carbonates, with the observed effervescence of , is a test for the carboxylic acid functional group.

They can also react with metals such as and forming carboxylate salts and hydrogen gas. These are not neutralisations as water is not formed, but are redox reactions.

When a carboxylic acid is deprotonated, a carboxylate anion is formed.

The pi bond electrons delocalise to include both oxygen atoms. This more delocalised system stabilises the charge making the loss of a proton in solution more thermodynamically feasible than in an alcohol’s .

The carboxylic acid group is trigonal planar about the carbonyl carbon, with bond angles approximately 120°.

Esters are generally volatile liquids with low boiling points; they do not form hydrogen bonds.

They often have pleasant, sweet or fruity odours. Many are used commercially in perfumes and flavourings.

Esters are also used as solvents and as plasticisers, which are added to rigid polymers, such as PVC, to make more flexible and softer materials.

Esters, RCOOR’, can be formed by a carboxylic acid and an alcohol.

The structures of both reactant molecules are recognisable in the ester structure.

Carboxylic acids react slowly and reversibly with alcohols in the presence of a strong acid catalyst to form esters.

A water molecule is eliminated. It forms from the group of the carboxylic acid and the of the alcohol’s group.

This is a condensation reaction.

When naming the ester product, the prefix comes from the alcohol, and the suffix comes from the carboxylic acid.

Glycerol (propane-1,2,3-triol) can be esterified with three long-chain carboxylic acids, 15–20 carbon atoms long, which may be saturated or unsaturated.

These ester products are known as triglycerides, and are found naturally in fats and oils.

Triglycerides have three ester bonds linking the glycerol carbon skeleton to the three fatty acids.

Fats are solids at room temperature, whereas oils are liquids. Both are formed as triesters of propan-1,2,3-triol (glycerol).

Animal fats tend to contain more saturated fatty acid groups and vegetable oils contain more unsaturated fatty acids.

Biodiesel is a renewable fuel composed of a mixture of the methyl esters of fatty acids.

Unmodified triglycerides (fats and oils) are more viscous and less volatile than the methyl esters of fatty acids; unmodified fats and oils are not suitable as fuels.

Biodiesel can be made by the alkaline-catalysed hydrolysis of vegetable oils.

Vegetable oils can be produced from renewable sources such as rapeseed oil. There is also potential to use waste vegetable oil from cooking.

The process of making biodiesel is a reversible reaction known as transesterification. This involves heating vegetable oil with methanol and a sodium hydroxide catalyst.

The methyl esters of the fatty acids (biodiesel) are formed as a layer above the less dense glycerol side product.

The reversible reaction is shifted towards the products through use of excess methanol.

The acid anhydride molecule consists of two acyl groups both bonded to the same oxygen.

An acid anhydride is produced by the dehydration of a carboxylic acid. They are named after the original carboxylic acid followed by the suffix ‘anhydride’.

Acyl chlorides have a similar structure to a carboxylic acid but with a chlorine atom instead of the group.

This highly electronegative forms a stable anion and is an excellent leaving group. This makes the acyl chloride very reactive, especially towards nucleophilic attack.

Amides have the general formula of .

A single hydrogen atom from the ammonia molecule is substituted by an acyl group, , forming a primary amide, .

If subsequent hydrogen atoms from a primary amine molecule are replaced by an alkyl group then a secondary amide or N-alkyl alkanamide is produced.

Secondary amides are also formed when a primary amine is acylated,

In the reaction between an acyl chloride and water:

• The oxygen in is the nucleophile.
• The leaving group is a chloride anion.

The reaction is nucleophilic addition–elimination. The attacking nucleophile is water, with the oxygen using its lone pair to bond to the carbonyl carbon.

The first stage is addition, with a formal negative charge on the carbonyl oxygen. The intermediate is saturated.

The second stage involves elimination of the small molecule , and the formation of the unsaturated product, ethanoic acid.

In the reaction between an acyl chloride and an alcohol:

• The oxygen in is the nucleophile.
• The leaving group is a chloride anion.

The reaction mechanism is nucleophilic addition–elimination. The attacking nucleophile is an alcohol, with the group’s oxygen, using its lone pair to bond to the carbonyl carbon.

The first stage is addition, with a formal negative charge on the carbonyl oxygen. The intermediate is saturated.

The second stage involves elimination of the small molecule and the formation of the unsaturated ester product.

In the reaction between an acyl chloride and ammonia:

• The nitrogen in is the nucleophile.
• The leaving group is a chloride anion.

The reaction mechanism is nucleophilic addition–elimination.

The attacking nucleophile is ammonia, with the nitrogen using its lone pair to bond to the carbonyl carbon. The first stage is addition, with a formal negative charge on the carbonyl oxygen. The intermediate is saturated.

The second stage involves elimination of the small molecule and the formation of the unsaturated primary amide product.

In the reaction between an acyl chloride and a primary amine:

• The nitrogen in is the nucleophile.
• The leaving group is a chloride anion.

The reaction mechanism is nucleophilic addition–elimination.

The attacking nucleophile is a primary amine, with the nitrogen using its lone pair to bond to the carbonyl carbon. The first stage is addition, with a formal negative charge on the carbonyl oxygen. The intermediate is saturated.

The second stage involves elimination of the small molecule and the formation of the unsaturated secondary amide product.

Acid anhydrides react with water to form carboxylic acids.

Ethanoic anhydride is hydrolysed in a nucleophilic addition–elimination reaction to form two molecules of ethanoic acid.

An acid anhydride reacts with an alcohol to form an ester and a molecule of free carboxylic acid in a nucleophilic addition–elimination reaction.

Acid anhydrides are more reactive than carboxylic acids so esterification takes place at room temperature in a non-reversible reaction. Heat is usually applied to increase the rate.

The carboxylic acid side product can be reused, or made into the anhydride again. This increases the reaction’s sustainability.

Acid anhydrides react readily with ammonia forming a primary amide.

The bond to nitrogen from ammonia replaces the bond on a carbonyl carbon. A molecule of carboxylic acid is also produced.

In the reaction of ethanoic anhydride with ammonia, the products are ethanamide, a primary amide, and ethanoic acid.

Acid anhydrides react with primary amines to form secondary amides and carboxylic acids.

In this nucleophilic addition–elimination reaction, the primary amine is the nucleophile.

Methylamine reacts with the acid anhydride, ethanoic anhydride, forming N-methyl ethanamide and ethanoic acid.

Both ethanoic anhydride and ethanoyl chloride are used industrially to prepare aspirin.

The starting material is salicylic acid, 2-hydroxybenzenecarboxylic acid. Compared to ethanoic acid, both ethanoic anhydride and ethanoyl chloride are more reactive and do not reach an equilibrium position with the ester produced.

There are several advantages of using the acid anhydride rather than the acyl chloride in drug synthesis.