Carboxylic acid derivatives undergo hydrolysis to convert back to carboxylic acids or carboxylate ions. They are also reduced into other functional groups.
All derivatives undergo hydrolysis under acidic or basic conditions to convert back to a carboxylic acid (or carboxylate). Carboxylate ions are formed in the hydrolysis of nitriles (compounds with a carbon triple bonded to a nitrogen), esters (compounds with a carboxyl unit in which a hydroxyl group is replaced by an alkyl or aryl group), or amides (compounds that contain a carbonyl, C=O, linked to a nitrogen through a C−N bond) in the presence of a base. Carboxylic acid derivatives are also used to convert to other derivatives.
Hydrolysis of Acid Derivatives
Acid halides and anhydrides are easily turned back into carboxylic acids in the presence of water. Nitriles, amides, and esters also are turned back into carboxylic acids in the presence of water and an acid or a base.
Organometallic reactions are conducted using carboxylic acid derivatives. An organometallic reaction is a nucleophilic addition reaction reaction with an organometallic reagent. The Grignard reagent is an example of an organometallic compound that contains a carbon bonded to a metal atom, in this case an alkyl group bonded to a magnesium atom bonded to a halide. The generic formula for a Grignard reagent is R−MgX.
Acid halides and anhydrides are converted to tertiary alcohols with Grignard or organolithium reagents and to ketones with lithium dialkyl cuprates. An acid halide is a compound characterized by a halide atom bonded to a carbonyl group. An acid anhydride is a compound formed when two carboxylic acids combine and water is lost.
Esters are converted to tertiary alcohols with the addition of Grignard or organolithium compounds. Organometallic reagents such as Grignards, organolithium reagents, and lithium dialkyl cuprates are excellent nucleophiles.
The nucleophilic alkyl group of the organometallic will attack the carbonyl carbon of an ester, acid halide, or anhydride to replace the leaving group (−X for acid halide; −OR′ for ester, and −OCOR′ for anhydride) with the alkyl group and form a ketone. With Grignards and organolithium reagents, a second nucleophilic attack will convert the resulting ketone into a tertiary alcohol. Lithium dialkyl cuprates are less reactive and will convert acid chlorides and anhydrides to ketones but cannot convert the ketone into a tertiary alcohol.
Nitriles are converted to ketones with the addition of Grignard or organolithium compounds. For nitriles, the nucleophilic organometallic reagent will convert the nitrile into an imine with the addition of the alkyl group, which is then converted to a ketone upon addition of an acid.
Grignard Reaction with Ester
Esters react with Grignard reagents to form tertiary alcohols.
Acid halides, acid anhydrides, and esters are converted to primary alcohols following the addition of a hydride called lithium aluminum hydride (LiAlH4 or LAH) and an acid workup. LAH is a powerful reducing agent that reduces any carbonyl to an alcohol by transferring one or more hydrogen atoms to the carbonyl carbon. Primary amides and nitriles are converted to primary amines with the addition of LAH. Secondary and tertiary amides are converted to secondary and tertiary amines, respectively, with the addition of LAH.
Lithium aluminum hydride (LiAlH4 or LAH) is used in a variety of reactions that reduce compounds, including carboxylic acid and its derivatives.
Acid halides and anhydrides are reduced to aldehydes with the addition of lithium tri(tert-butoxy) aluminum hydride. Esters are reduced to aldehydes with the addition of diisobutylaluminum hydride (DIBAL-H). The aluminum atom is an electrophile and is attacked by the nucleophilic oxygen atom of the carbonyl, which makes the carbonyl carbon even more electrophilic.
DIBAL-H Mechanism
DIBAL-H reduces an ester to an aldehyde and an alcohol.
