20.6 Reactions of Carboxylic Acids: An Overview

Carboxylic acids are versatile organic compounds with a range of important reactions. From nucleophilic acyl substitutions to reductions and decarboxylations, these reactions showcase the diverse chemistry of the carboxyl group.

Understanding carboxylic acid reactions is crucial for grasping organic synthesis. These reactions highlight the reactivity of the carbonyl group and provide key tools for transforming carboxylic acids into other functional groups like alcohols and esters.

Reactions of Carboxylic Acids

Categories of carboxylic acid reactions

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• Nucleophilic acyl substitution reactions involve a nucleophile attacking the electrophilic carbonyl carbon resulting in substitution of the hydroxyl group with the nucleophile (alcohols, amines, ammonia)
• Reduction reactions add hydrogen to the carbonyl carbon using reducing agents (lithium aluminum hydride (LiAlH4), borane (BH3)) forming primary alcohols
• Decarboxylation removes the carboxyl group as carbon dioxide (CO2) through heat, enzymatic reactions, or strong acids/bases yielding the corresponding alkane or alkene
• Substitution at the α-carbon replaces the α-hydrogen with an electrophile facilitated by an enolate ion intermediate (α-halogenation, Hell-Volhard-Zelinsky reaction)
• Esterification reactions form esters by reacting carboxylic acids with alcohols

Reduction to primary alcohols

• Strong reducing agents (lithium aluminum hydride (LiAlH4), borane (BH3)) reduce carboxylic acids to primary alcohols
• LiAlH4 is a powerful hydride donor that reduces the carbonyl group to a primary alcohol in anhydrous ether or tetrahydrofuran (THF) under inert atmosphere
  • Mechanism: nucleophilic addition of hydride to the carbonyl carbon followed by protonation during aqueous workup
• Borane (BH3) is a milder reducing agent used in THF
  • Resulting alkylborane intermediate is oxidized using hydrogen peroxide (H2O2) to yield the primary alcohol
• Two-step reduction process:
  1. Nucleophilic addition of hydride to the carbonyl carbon
  2. Protonation of the resulting alkoxide ion during aqueous workup

Reactivity vs alcohols and ketones

• Carboxylic acids are more reactive than alcohols and ketones
• Nucleophilic acyl substitution reactivity:
  • Carboxylic acids readily undergo substitution due to the electrophilic carbonyl carbon and hydroxyl group being a good leaving group
  • Alcohols and ketones are less susceptible due to the absence of a good leaving group
• Acid-base properties:
  • Carboxylic acids are weak acids (pKa 4-5) due to the electron-withdrawing carbonyl group stabilizing the conjugate base (carboxylate ion)
  • Alcohols and ketones are not acidic under normal conditions lacking a strongly electron-withdrawing group
• Reduction:
  • Carboxylic acids are reduced to primary alcohols using strong reducing agents (LiAlH4, BH3)
  • Ketones are reduced to secondary alcohols using milder reducing agents (sodium borohydride (NaBH4), catalytic hydrogenation)
  • Alcohols require conversion to a better leaving group (tosylate, halide) before reduction to hydrocarbons

Carboxylic Acid Derivatives and Reactions

• Acid anhydrides are formed by the condensation of two carboxylic acid molecules
• The carbonyl group in carboxylic acids is responsible for their reactivity and chemical properties
• Carboxylic acids can undergo oxidation reactions to form various products depending on the oxidizing agent used
• The acidity of carboxylic acids is influenced by substituents and structural factors