Third Trimester
Carboxylic Acid Derivatives Reactions
Carboxylic acid derivatives include esters, amides, anhydrides, and acyl chlorides. These compounds can undergo a variety of reactions, often converting into each other or back to the carboxylic acid under different conditions.
1. Intramolecular Reactions
Intramolecular reactions involve the reactants forming a ring structure, typically when a molecule has functional groups that can react with each other. Common intramolecular reactions include:
Lactonization: Formation of a lactone (cyclic ester) from a hydroxy acid.
Lactamization: Formation of a lactam (cyclic amide) from an amino acid.
For example, the intramolecular cyclization of γ- or δ-hydroxy acids leads to the formation of γ- or δ-lactones.
2. Grignard Reagents
Grignard reagents (RMgX) are used to form carbon-carbon bonds by reacting with electrophiles. In the context of carboxylic acids and their derivatives:
Reaction with Carbonyl Compounds: Grignard reagents add to carbonyl compounds (aldehydes, ketones, esters) to form alcohols.
Esters to Tertiary Alcohols: Esters react with Grignard reagents to form tertiary alcohols after a subsequent hydrolysis step.
3. Reduction with LiAlH4 and LiAlH(OR)3
Lithium aluminum hydride (LiAlH4) and its derivatives are strong reducing agents used to reduce carboxylic acid derivatives to alcohols.
LiAlH4: Reduces esters, amides, and carboxylic acids to primary alcohols.
LiAlH(OR)3: A milder reducing agent used for selective reductions, typically reducing esters to alcohols but being less reactive towards other functional groups.
Summary of Key Reactions
Intramolecular Cyclization:
Hydroxy acid to lactone (acid catalysis).
Amino acid to lactam (acid or base catalysis).
Grignard Reaction:
Ester + RMgX → Tertiary alcohol (after hydrolysis).
Example: Ethyl acetate + 2 equivalents of methylmagnesium bromide → 2-methyl-2-pentanol.
Reduction with LiAlH4 and LiAlH(OR)3:
Ester + LiAlH4 → Primary alcohol.
Amide + LiAlH4 → Amine.
Carboxylic acid + LiAlH4 → Primary alcohol.
Ester + LiAlH(OR)3 → Primary alcohol (milder conditions).