3. Carboxylic Acids & Derivatives
Carboxylic acids and their derivatives — acid chlorides, anhydrides, esters, amides — all react by nucleophilic acyl substitution: attack at the carbonyl, then the leaving group departs. Their reactivity order is the key to the whole family.
Reactivity Order
$$\text{Acid chloride} > \text{anhydride} > \text{ester} > \text{amide} > \text{carboxylate}$$ A more reactive derivative converts to any less reactive one; the reverse needs stronger conditions.
Fischer Esterification and Hydrolysis
Example: $$\text{CH}_3\text{COOH} + \text{CH}_3\text{CH}_2\text{OH} \xrightarrow{\text{H}^+} \text{CH}_3\text{COOCH}_2\text{CH}_3 + \text{H}_2\text{O}$$
Ethyl acetate from acetic acid and ethanol. The reverse — ester hydrolysis with aqueous NaOH, then acid — is saponification when the ester is a fat.
Reduction and Amide Formation
LiAlH4 reduces esters and acids to primary alcohols (ethyl acetate → two molecules of ethanol). Acid chlorides plus ammonia or amines give amides — the peptide bond is an amide.
Practice Problems
- What is the product of acetyl chloride + NH3?
- What do you get from hydrolyzing methyl benzoate with NaOH, then acid?
- Which carboxylic acid derivative is the most reactive?
- What does LiAlH4 reduction of butanoic acid give?
Answers: 1. Acetamide 2. Benzoic acid + methanol 3. Acid chloride 4. 1-butanol