Preparation of Anhydrides

Anhydrides are prepared by dehydration of carboxylic acids either at extremely high temperatures (800 ^oC) or by using P₂O₅ as a dehydrating agent:

For most carboxylic acids are not compatible with excessive heating, and even using P₂O₅ is not a practically applicable solution. Therefore, the most common method for preparing carboxylic anhydrides in the laboratory is the conversion of the acid to an acid chloride and a carboxylate salt, which react readily at room temperature:

Reactions of Anhydrides

Although slightly less reactive than acid chlorides, anhydrides react with all the nucleophiles in an identical mechanism.

The only difference in these nucleophilic acyl substitutions is the change of the leaving group from chloride to a carboxylate.

Hydrolysis of Anhydrides

Anhydrides can be hydrolyzed to carboxylic acids. Adding a base would increase the rate of the conversion:

Esters from Anhydrides

Anhydrides can be converted into esters by using an alcohol with a base or, even better, an alkoxide which is a stronger nucleophile:

In a similar reaction, thioesters can be prepared from anhydrides:

Amides from Anhydrides

Amines, being good nucleophiles, react readily with anhydrides to form primary, secondary or tertiary amides:

Anhydrides in Grignard Reaction

Just like the acid chlorides and esters, anhydrides react with excess Grignard reagent, forming a tertiary alcohol:

Reduction of Anhydrides

Anhydrides can be reduced to a primary alcohol using LiAlH₄:

To stop the reduction at the aldehyde, a less powerful reducing agent such as lithium tri(t-butoxy) aluminum hydride LiAl(O^tBu)₃H can be used:

Check Also

Preparation and Reaction Mechanisms of Carboxylic Anhydrides