With less basic nucleophiles, especially under acidic conditions, substitution through the addition-elimination mechanism may occur.

In the esterification of a carboxylic acid, an alcohol and a carboxylic acid react in the presence of acid to form an ester and water.

The acid serves to protonate both the carbonyl oxygen, activating the carbonyl towards nucleophilic addition, and the carboxy OH, converting it into a better leaving group.

Carboxylic Acid Derivatives: Alkanoyl (Acyl) Halides

19-8

Alkanoyl (acyl) halides are formed by using inorganic derivatives of carboxylic acids.

Alkanoyl (acyl) halides can be prepared from carboxylic acids by using reagents such as SOCl2 or PBr3.

The reaction with either reagent begins with the conversion of the poor leaving group, -OH, into a good leaving group.

Acids combine with alkanoyl halides to produce anhydrides.An alkanoyl halide is activated to attack by weaker nucleophiles by the electronegative power of its halogen atom.

Treatment of alkanoyl halides with carboxylic acids leads to carboxylic anhydrides.

5- or 6-membered cyclic anhydrides can be prepared by simple heating of the corresponding dicarboxylic acids.

Because the halogen in an alkanoyl halide and the RCO2 group in an anhydride are good leaving groups, alkanoyl halides and anhydrides are often useful intermediates during the preparation of other compounds.

Carboxylic Acid Derivatives: Esters19-9Carboxylic acids react with alcohols to form esters.

Esters can be formed in an equilibrium process by combining a carboxylic acid and an alcohol in the presence of catalytic amounts of a mineral acid.

Ho is usually close to 0 for an esterification reaction. Since So is also close to zero, Go will be close to zero and the equilibrium constant for the reaction will be close to 1.

The equilibrium can be shifted in the direction of the products by using an excess of one of the starting materials, or by removing either water or the ester from the reaction mixture.

Esterifications are most often carried out using the alcohol as the solvent.

Esterifications are most often carried out using the alcohol as the solvent.

Etherification proceeds through acid-catalyzed addition-elimination.Acid catalysis in an esterification reaction functions first to protonate the carbonyl oxygen, making the carbonyl carbon a better electrophile, and then to protonate the –OH group in the tetrahedral intermediate making it a better leaving group.

All of the steps are reversible.

Addition of alcohol or removal of water favors esterification.

Hydroxy acids may undergo intramolecular esterification to lactones.Hydroxy carboxylic acids may form 5- or 6-membered cyclic esters, or lactones, when treated with catalytic amounts of mineral acid through a process called intramolecular esterification.