Acid Derivatives: Esters, Acid Chlorides, Amides, Anhydrides
Carboxylic acid derivatives are compounds in which the –OH of a carboxylic acid is replaced by another group: acid chlorides (–COCl), acid anhydrides (–CO–O–CO–), esters (–COOR) and amides (–CONH2). All four share the same acyl group (R–C=O) and interconvert through one common mechanism.
They matter because almost every acyl-transfer reaction in the lab and in industry goes through one of these: aspirin is made from an anhydride, polyesters and nylon are built from esters and amides, and acid chlorides are the most reactive acylating agents available. The key skill is knowing their reactivity order, which decides which derivative can be made from which.
Key Concepts
- Nucleophilic acyl substitution: the common mechanism — a nucleophile attacks the carbonyl carbon, a tetrahedral intermediate forms, and the leaving group is expelled to regenerate C=O.
- Reactivity order: acid chloride > acid anhydride > ester > amide. A more reactive derivative can always be converted into a less reactive one, never the reverse directly.
- Leaving-group ability: Cl− is the best leaving group (weakest base), which is why acid chlorides are the most reactive; NH2− is a terrible leaving group, making amides the least reactive.
- Acyl group: the R–CO– fragment transferred in all these reactions.
How It Works
Step 1 — attack. The nucleophile (water, alcohol, ammonia or amine) attacks the electrophilic carbonyl carbon of the derivative, forming a tetrahedral intermediate with the nucleophile, the R group, the original leaving group and O− all on one carbon.
Step 2 — collapse. The C=O double bond reforms, pushing out the leaving group: chloride from an acid chloride, carboxylate from an anhydride, alkoxide from an ester, or amide ion from an amide. Because the leaving groups get progressively worse bases in the order Cl− → RCOO− → RO− → NH2−, reactivity falls in exactly the same order.
Making the derivatives. Acids give acid chlorides with SOCl2 or PCl5; anhydrides from acid chloride + carboxylate salt; esters by Fischer esterification; amides from acid chloride or anhydride + ammonia.
Worked Example
Aspirin (acetylsalicylic acid, C9H8O4, molar mass 180 g/mol) is made from salicylic acid (C7H6O3, 138 g/mol) and acetic anhydride. If 138 g of salicylic acid gives 150 g of aspirin, what is the percentage yield?
- 138 g of salicylic acid = 138 ÷ 138 = 1.00 mol.
- The acetylation is 1:1, so the theoretical yield = 1.00 mol × 180 g/mol = 180 g of aspirin.
- Actual yield = 150 g.
- Percentage yield = (150 ÷ 180) × 100 = 83.3%.
Common Misconceptions
- "Amides hydrolyze as easily as esters." Wrong. Amides are the least reactive derivatives; hydrolysis needs prolonged heating with strong acid or base, whereas esters hydrolyze much more readily.
- "You can convert an amide directly into an acid chloride." Wrong. Reactions only go downhill in reactivity — amides can be hydrolyzed back to the acid (with effort), and the acid is then converted to the chloride.
- "Esters are unreactive because they smell nice." Wrong. Esters sit in the middle of the reactivity order and undergo transesterification, saponification and aminolysis quite readily.
Real-World Applications
- Aspirin: made industrially by acetylating salicylic acid with acetic anhydride — one of the highest-volume drugs in history.
- Polyesters (PET): ester linkages join the monomers of plastic bottles and polyester fabric.
- Nylon: amide linkages join the monomers of nylon-6,6, used in textiles, ropes and engineering plastics.
In short, the four acid derivatives all react by nucleophilic acyl substitution, and their reactivity falls in the order acid chloride > anhydride > ester > amide because the leaving group gets progressively worse. Learn that one order and you can predict every interconversion.