anhydride
Summary
An anhydride (acid anhydride) is a carboxylic acid derivative with two acyl groups joined through one oxygen, RC(=O)–O–C(=O)R, formally two acids minus water. It is a reactive acylating agent: more reactive than esters and amides, less than acyl chlorides.
Detail
Meaning: An anhydride has two acyl groups bonded to the same oxygen, RC(=O)–O–C(=O)R. It is formally two carboxylic acids joined with loss of one water. Dicarboxylic acids that can close a five- or six-membered ring (succinic, phthalic) form cyclic anhydrides on heating. Anhydrides react by nucleophilic acyl substitution: the nucleophile adds to a carbonyl carbon, forming a tetrahedral intermediate, and a carboxylate leaves. Carboxylate is a good leaving group because it is a weak, resonance-stabilized base, so anhydrides are good acylating agents.
Equation: 2 RCOOH → (RCO)₂O + H₂O, where R is an alkyl or aryl group (no unit) and each RCOOH is a carboxylic acid. The reverse reaction with water is hydrolysis.
On the MCAT: Expect a reactivity ranking of acyl chloride > anhydride > ester ≈ carboxylic acid > amide, with the rule that a more reactive derivative can be converted into a less reactive one. Predict products: anhydride + water gives two acids; + alcohol gives an ester plus an acid; + amine gives an amide plus an acid. Acetic anhydride acetylating salicylic acid to make aspirin is a common example.
Common confusion: An anhydride is not an ester, because its bridging oxygen links two carbonyl carbons. In acyl substitution only one acyl group is transferred, and the other leaves as a carboxylic acid or carboxylate.
Sources
- Organic Chemistry (Wade)
- Organic Chemistry (Klein)
- Organic Chemistry (McMurry)
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.