Acylation

Quick Notes

• Acid anhydrides, acyl chlorides, and amides are key compounds in acylation.
• Acyl chlorides and acid anhydrides react with nucleophiles via nucleophilic addition–elimination.
• Common reactions:
  • Acyl Chloride + Water (H₂O) → Produces carboxylic acid
  • Acyl Chloride + Alcohol (ROH) → Produces ester
  • Acyl Chloride + Ammonia (NH₃) → Produces amide
  • Acyl Chloride + Primary amines (RNH₂) → Produces N-substituted amide
• Ethanoic anhydride is preferred over ethanoyl chloride in aspirin manufacture due to cost and safety benefits, as ethanoyl chloride (an acyl chloride) is highly reactive.

Full Notes

Acylation involves transferring an acyl group (RCO) to a compound, usually forming an ester or amide. There are several key reactions you need to know, involving acid anhydrides, acyl chlorides and amides.

Structures of Key Acyl Compounds

Acid Anhydrides (RCO)₂O:

Formed from two carboxylic acid molecules in a condensation reaction (water molecule is produced).

Acyl Chlorides (RCOCl):

Derived from carboxylic acids, highly reactive.

Amides (RCONH₂):

Contain a carbonyl group bonded to an amine.

Nucleophilic Addition-Elimination Reactions

Acyl chlorides and acid anhydrides react with nucleophiles via nucleophilic addition–eliminations (see below for mechanism outline).

Acid anhydrides react similarly to acyl chlorides but produce carboxylic acids instead of HCl.

Common reactants:

• Water (H₂O) → Produces carboxylic acid
• Alcohol (ROH) → Produces ester.
• Ammonia (NH₃) → Produces amide.
• Primary amines (RNH₂) → Produces N-substituted amide.

Acid anhydride reactions

Acyl chloride reactions

Nucleophilic Addition-Elimination Mechanism

Because of the partially positively charged carbon in the C=O group, acyl chlorides react with nucleophiles in addition–elimination reactions.

• Step 1: Nucleophile attracted to δ⁺ C in the C=O bond in the acyl chloride and uses lone pair of electrons to form bond to C
• Step 2: C=O double bond breaks, with bonding pair of electrons going to the oxygen
• Step 3: Carbon–oxygen bond reforms as carbon–chlorine bond breaks
• Step 4: Nu–H bond breaks

Industrial Advantages of Ethanoic Anhydride Over Ethanoyl Chloride

• Ethanoic anhydride is Less reactive than ethanoyl chloride, meaning it is safer to handle and store.
• Also heaper than ethanoyl chloride.
• No toxic HCl fumes produced when ethanoic anhydride is used, compared to ethanoyl chloride.
• Used in aspirin synthesis (esterification with salicylic acid).

Summary Table: Reactions of Acyl Compounds