Acylation (AQA A Level Chemistry): Revision Note

Acyl Groups

Acyl groups

• Acyl groups can be introduced into many molecules using acyl chlorides or acid anhydrides, which are known as acylating agents

• Acyl chlorides are derivatives of carboxylic acids in which the –OH group has been substituted by a chlorine atom

  • They are named by identifying the parent hydrocarbon chain and adding the suffix –oyl chloride

  • Alternatively, they can be named by removing –oic acid from the corresponding carboxylic acid name and replacing it with –oyl chloride

• Acid anhydrides are also derivatives of carboxylic acids, formed when the –OH group is replaced by an alkanoate group

  • They are named by identifying the parent hydrocarbon chain and adding the suffix –oic anhydride

  • This can also be done by removing –oic acid from the carboxylic acid name and adding –oic anhydride

Nucleophilic Addition–Elimination

• Acyl chlorides and acid anhydrides are very reactive organic compounds that undergo a range of reactions, including nucleophilic addition–elimination reactions

• In a nucleophilic addition–elimination reaction, a nucleophile adds to the C=O bond, followed by the elimination of a small molecule

• Examples of nucleophilic addition–elimination reactions of acyl chlorides include:

  • Hydrolysis

  • Reaction with alcohols to form esters

  • Reaction with ammonia or primary amines to form amides

Hydrolysis

• The hydrolysis of acyl chlorides produces a carboxylic acid and hydrogen chloride (HCl)

• This reaction is a nucleophilic addition–elimination reaction in which a water molecule adds across the C=O bond, followed by the elimination of an HCl molecule

• For example, the hydrolysis of propanoyl chloride forms propanoic acid and HCl

• The hydrolysis of acid anhydrides produces two molecules of the carboxylic acid

  (CH₃CO)₂O + H₂O 2CH₃COOH

Formation of esters

• Acyl chlorides react with alcohols to form esters

• This esterification reaction is a nucleophilic addition–elimination reaction in which the alcohol adds across the C=O bond, followed by the elimination of a hydrogen chloride (HCl) molecule

• Acid anhydrides react with alcohols to form esters and a carboxylic acid:

(CH₃CO)₂O + CH₃OH CH₃COOCH₃ + CH₃COOH

Formation of amides

• Acyl chlorides react with ammonia or primary amines to form amides in a condensation reaction

• A lone pair on the nitrogen atom attacks the carbonyl carbon in the acyl chloride

• The reaction proceeds via a nucleophilic addition–elimination mechanism:

  • The nucleophile adds to the C=O bond

  • A chloride ion (Cl⁻) is eliminated

  • Hydrogen chloride (HCl) is formed

What happens to the HCl?

• The HCl formed does not remain unreacted.

• It is immediately neutralised by a second molecule of ammonia or amine present in excess

• This forms an ammonium salt (e.g., NH₄Cl or CH₃NH₃Cl)

Why are two molecules of ammonia/amine needed?

• The 1st molecule of ammonia/amine forms the amide

• The 2nd molecule of ammonia/amine neutralises the HCl and forms an ammonium salt

Example reactions

• Reaction with ammonia

• Product: Primary amide (propanamide) and ammonium chloride

CH₃CH₂COCl + 2NH₃ → CH₃CH₂CONH₂ + NH₄Cl

• Reaction with methylamine

• Product: Secondary (substituted) amide and methylammonium chloride

CH₃COCl + 2CH₃NH₂ → CH₃CONHCH₃ + CH₃NH₃Cl

• Reaction with ethylamine

• Product: Secondary (substituted) amide and ethylammonium chloride

CH₃COCl + 2CH₃CH₂NH₂ → CH₃CONHCH₂CH₃ + CH₃CH₂NH₃Cl

Acid anhydrides react with ammonia and with amines

• Acid anhydrides react with ammonia or primary amines to form amides in a condensation reaction

• A lone pair on the nitrogen atom attacks the carbonyl carbon in the acid anhydride

• With ammonia, the product is an amide and an amide salt:

(CH₃CO)₂O + 2NH₃ CH₃CONH₂ + CH₃CONH₄⁺

• With a primary amine, the product is an N-substituted amide and the amide salt:

(CH₃CO)₂O + 2RNH₂ CH₃CONHR + CH₃CORNH₃⁺

Summary for the formation of amides

• With acyl chlorides, all reactions form HCl, which is not observed as a separate product

  • The HCl is neutralised by excess ammonia or amine

  • The final products are an amide and an ammonium salt

• With acid anhydrides, the products are amides or N-substituted amides

Nucleophilic Addition–Elimination Mechanism

• The general mechanism of these nucleophilic addition-elimination reactions involves two steps:

  • Step 1 - Addition of a nucleophile across the C=O bond

  • Step 2 - Elimination of a small molecule such as HCl or H₂O

Mechanism of hydrolysis of acyl chlorides

• In the hydrolysis of acyl chlorides, the water molecule acts as a nucleophile

  • Step 1 - Nucleophilic addition; the lone pair on the oxygen atoms carries out an initial attack on the carbonyl carbon

  • Step 2 - Elimination; this is followed by the elimination of a hydrochloric acid (HCl) molecule

Formation of esters: reaction mechanism

• In the esterification reaction of acyl chlorides, the alcohols act as nucleophiles

  • Step 1 - Nucleophilic addition; the lone pair on the oxygen atoms carries out an initial attack on the carbonyl carbon

  • Step 2 - Elimination; this is again followed by the elimination of an HCl molecule

Formation of amides: reaction mechanism

• The nitrogen atom in ammonia and primary amines acts as a nucleophile

  • Step 1 - Nucleophilic addition; the lone pair on the nitrogen atoms carries out an initial attack on the carbonyl carbon

  • Step 2 - Elimination; this is followed by the elimination of an HCl molecule

  • Step 3 - Acid-Base reaction; the HCl formed would immediately react with excess ammonia to give ammonium chloride in an acid-base reaction