Nucleophilic acyl substitution
A carboxylic acid derivative has a leaving group on a carbonyl carbon. A nucleophile adds to C=O, then the C=O reforms and the leaving group leaves. Acid chlorides are most reactive, then anhydrides, esters, amides.
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Analogy
A turnstile: you enter, push through, and something else exits at the other side.
Example
CH₃COOH + CH₃CH₂OH ⇌ CH₃COOCH₂CH₃ + H₂OAcid catalyst, heatProduct: ethyl ethanoate
In practice
Esters, which smell like fruit, are made by heating a carboxylic acid with an alcohol and an acid catalyst (Fischer esterification).
Practice
Interview questions
- Describe how to convert ethanol into ethyl ethanoate, and say why the reaction is reversible.
- Oxidise ethanol to ethanoic acid
- Heat with ethanol and acid catalyst
- Esterification forms water
- Reaction reaches equilibrium, remove water for better yield
Questions people ask
Why do acid chlorides react faster than amides?
Chloride is a good leaving group and is weakly basic. Amides hold a poor leaving group, and the nitrogen lone pair is shared with the carbonyl by resonance, which makes the carbon less electrophilic. So acid chlorides react quickly and amides are the most stable of the derivatives.
Why is Fischer esterification reversible?
Ester formation produces water, and the reverse reaction, hydrolysis, uses water to break the ester. At equilibrium both occur. To get a high yield, use an excess of one reactant or remove the water as it forms, following Le Chatelier's principle.