Organic Chemistry: Carboxylic Acid Derivatives

Carboxylic Acid Derivatives

• Defined as compounds with functional groups that can be converted to carboxylic acids by a simple acidic or basic hydrolysis

Esters

• Carboxylic acid derivatives with a hydroxy group (—OH) replaced by an alkoxy (—OR) group
• Cyclic esters are called lactones

Amides

• Composite of a carboxylic acid and ammonia or an amine
• Ammonium salts are converted to amides at high temperatures with loss of H2O
• Cyclic amides are called lactams

Nitriles

• Contain the cyano group (—CN)
• Electronic structure of nitriles: the atoms at the ends of the triple bonds are sp hybridized, and the bond angle is 180°

Acid Halides

• Also called acyl halides
• "Activated" derivatives (highly electrophilic) used in the synthesis of other acyl compounds such as esters

Acid Anhydrides

• Contain two molecules of acid, with loss of a molecule of water
• "Activated" derivatives of carboxylic acids (highly electrophilic)

Spectroscopy of Carboxylic Acid Derivatives

• IR spectroscopy: most acid derivatives have C=O stretches between 1700 cm–1 and 1800 cm–1
• 1H NMR spectroscopy: proton chemical shifts are close to those of similar protons in ketones, aldehydes, alcohols, and amines
• 13C NMR spectroscopy: useful for determining the structure of acid derivatives

Nucleophilic Acyl Substitution

• Interconversion of acid derivatives occurs by nucleophilic acyl substitution
• Proceeds via an addition–elimination mechanism
• More reactive derivatives can be converted to less reactive derivatives

Reactivity of Carboxylic Acid Derivatives

• Acid chlorides are the most reactive, followed by anhydrides, esters, and amides
• Nitriles are the least reactive

Interconversion of Carboxylic Acid Derivatives

• Acid chlorides can be converted to anhydrides, esters, and amides
• Anhydrides can be converted to esters and amides
• Esters can be converted to amides
• Amides can be converted to esters and acid chlorides

Leaving Groups in Nucleophilic Acyl Substitutions

• A strong base, such as an alkoxide (–OR), is not usually a leaving group, except in an exothermic step
• In the nucleophilic acyl substitution of esters, the elimination of the alkoxide is highly exothermic, converting the tetrahedral intermediate into a stable molecule

Transesterification

• One alkoxy group can be replaced by another with acid or base catalyst
• Use a large excess of the desired alcohol to displace the equilibrium

Hydrolysis of Acid Derivatives

• Acid chlorides and anhydrides are hydrolyzed quickly, even in moist air with no acid or base catalyst
• Esters are hydrolyzed to carboxylic acids under basic conditions (saponification)
• Amides are hydrolyzed to carboxylic acids under acidic or basic conditions
• Nitriles are hydrolyzed to carboxylic acids under acidic or basic conditions

Reduction of Acid Derivatives

• Lithium aluminum hydride (LiAlH4) reduces esters, acids, and acyl chlorides to primary alcohols
• Lithium tri-tert-butoxyaluminum hydride is a milder reducing agent that reacts faster with acyl chlorides than with aldehydes
• Di-isobutylaluminum hydride (DIBAL-H) is a mild reducing agent that reduces esters to aldehydes at -78 °C
• Amides can be reduced to amines using LiAlH4

Organometallic Reagents

• Grignard and organolithium reagents add twice to acid chlorides and esters to give alcohols after protonation
• Dialkylcuprate reagents (Gilman reagents) react with acid chlorides to give ketones

Synthesis of Acid Derivatives

• Acid chlorides can be synthesized using thionyl chloride (SOCl2), oxalyl chloride (COCl)2, and phosgene (COCl2)
• Anhydrides can be synthesized by reacting an acid chloride with a carboxylic acid or a carboxylate salt
• Esters can be synthesized by reacting an acid chloride with an alcohol
• Amides can be synthesized by reacting an acid chloride with ammonia or an amine
• Nitriles can be synthesized by reacting an acid chloride with a cyanide ion

Test your knowledge of carboxylic acid derivatives, nitriles, and anhydrides in organic chemistry. Learn about the characteristics and reactions of these compounds.