Reactions of Carboxylic Acid Derivatives

Preparation of Acid Halides and Acid Anhydrides

Acid halides and acid anhydrides are two types of carboxylic acid derivatives that can be prepared through a variety of methods.
An acid halide is an organic compound that contains a carbonyl group (C=O{\rm {C{=}O}}) bound to one alkyl (R{-}{\rm {R}}) fragment and one halogen atom, with RC(=O)X{\rm{RC({=}O) X}} or RCOX{\rm {R{-}COX}} stoichiometry. For example, propanoyl chloride is a three-carbon acid chloride. Acid halides are prepared by a reaction of a carboxylic acid with thionyl chloride (SOCl2) or phosphorus tribromide (PBr3). In the reaction with thionyl chloride, the oxygen from the carbonyl attacks the sulfur atom, and one of the chlorine atoms leaves the thionyl chloride. The compound rearranges to have another chlorine atom and a sulfur dioxide (SO2) molecule leave, yielding an acid chloride. In the reaction with phosphorus tribromide, the reaction is similar in that the oxygen from the carbonyl attacks the phosphorus atom. The result is a substitution of the hydroxyl with a bromide group.

Acid Chloride Formation via Thionyl Chloride

Carboxylic acids react with thionyl chloride to substitute the hydroxyl group with a chloride atom.

Acid Halide Formation via Phosphorus Tribromide

Phosphorus tribromide is used to substitute a bromide group for the hydroxyl group in a carboxylic acid, yielding an acid halide.
Acid anhydrides are oxides that form an acid in water. They are prepared via the dehydration of an acid or diacid (a molecule containing two acidic functional groups). Dehydration is the loss of a water molecule. The hydrogen from the hydroxyl group of one carboxylic acid and the hydroxyl group from a second carboxylic acid are removed to become water. The oxygen from the hydroxyl group of one carboxylic acid will attack the acidic hydrogen of another carboxylic acid. The resulting carboxylate will attack the carbonyl of the protonated carboxylic acid, generating the carboxylic anhydride and a water molecule. Heat causes the reaction to proceed toward the product. In the case of a diacid, this all occurs within the same structure.

Preparation of Acid Anhydride via Dehydration of Carboxylic Acids

Under heat, two carboxylic acids are joined to form an acid anhydride and a water molecule. This does not result in the loss of any carbon atoms in the overall structure.

Preparation of Acid Anhydride via Dehydration of a Diacid

Under heat, two carboxylic acids within the same structure are joined to form a cyclic acid anhydride and a water molecule. This does not result in the loss of any carbon atoms in the overall structure.
Acid anhydrides are also prepared via the addition of a carboxylate to an acid chloride in the presence of a base. The hydroxyl group from the base attacks the proton found on the carboxylic acid, yielding a carboxylate ion. The carboxylate ion attacks the carbonyl carbon of the acid chloride. This intermediate rearranges so that the chloride is the leaving group, yielding an acid anhydride. Because halides are such good leaving groups, the nucleophilic oxygen can attack the electrophilic carbonyl carbon and cleave the carbon-chlorine bond.

Acid Anhydride Preparation with Carboxylic Acid and Acid Chloride

In the creation of an anhydride, a carboxylic acid is deprotonated to a carboxylate ion (COO{\rm{COO}}{-}), which attacks the acid chloride, resulting in a structure that contains the carbon atoms from the carboxylic acid and the carbon atoms from the acid chloride.