Chapter 21: Carboxylic acids derivatives

Reactivity of carboxylic acid derivatives

• Acid chloride > Acid anhydride > Thioesters > ester > amide

• Acid chloride is more reactive

• The less hindered—→ the more reactive

Reactions of carboxylic acids: To form acid halides

• Reagents: SOCl2/ pry or PBr3/pry

• Product: Cl or Br replaces OH

Reactions of carboxylic acids: to form acid anhydrides

Reactions of carboxylic acids: To form esters, SN2 reaction

Reaction of a carboxylic acid with 1.NaOH 2. Alkyl halide or alkyl modulate to give an ester mechanism

Reactions of carboxylic acids: Fisher esterification reaction

Reactions of carboxylic acids: To form amides

• Reagent DCC/ primary amine

Reactions of carboxylic acids: to alcohols (reduction)

• Reagents: 1. LiAlH4, ether 2. H3O+ , reduces all ketones

• Reagents: 1. BH3/THF 2. H3O+ , reduces only COOH

Reaction of Acid chlorides: Hydrolysis

Acid Chloride Hydrolysis Mechanism

Reaction of Acid chlorides: To form anhydrides

Reaction of Acid chlorides: Alcoholysis

Reaction of Acid chlorides: Aminolysis

Reaction of Acid chlorides: To form alcohols (reduction)

Reaction of Acid chlorides: with organometallic reagents

Acid Chloride with excess Grignard mechanism

Reaction of Acid anhydrides: Alcoholysis

Summary of Reaction of Acid Anhydrides

Preparations of Esters

Summary Reactions of Esters

Reaction of an ester with an amine mechanism

Reaction of amides:

Cyclic Esters = lactones

Cyclic Amides: lactams