Overview
This lecture covers carboxylic acid derivatives, their reactivity, and major reactions such as nucleophilic acyl substitution and hydrolysis, with biological and industrial examples.
Vitamin C and Esters in Biology
- Esters are found in perfumes, fruit scents, and key biomolecules like vitamin C (ascorbic acid).
- Vitamin C acts as an antioxidant and is essential for collagen synthesis.
- Vitamin C deficiency causes scurvy, prevented by citrus fruits due to their vitamin C content.
Carboxylic Acid Derivatives and Reactivity
- Four main carboxylic acid derivatives: acid chlorides, anhydrides, esters, and amides.
- Reactivity is influenced by inductive effects (electron withdrawal) and resonance effects (electron donation).
- Acid chlorides are the most reactive due to strong inductive effects and poor resonance stabilization.
- Anhydrides are less reactive than acid chlorides, followed by esters, with amides being the least reactive due to strong resonance.
Nucleophilic Acyl Substitution Reactions
- Carboxylic acid derivatives undergo nucleophilic acyl substitution via an addition-elimination mechanism.
- Unlike aldehydes and ketones, these derivatives have good leaving groups that facilitate substitution.
- Reactions are significant in making plastics (like nylon) and biological molecules (like proteins and fats).
Hydrolysis of Carboxylic Acid Derivatives
- Hydrolysis breaks carboxylic acid derivatives into carboxylic acids or their salts.
- Acid chlorides and anhydrides hydrolyze with just water; esters and amides need acid or base catalysis.
- Base-catalyzed ester hydrolysis (saponification) produces soap by forming carboxylate ions.
- Acid-catalyzed hydrolysis avoids forming unstable negative charges and leads to alcohol and carboxylic acid products.
Biological and Industrial Examples
- Triglycerides (fats) are made from glycerol and carboxylic acids, linked by ester bonds.
- Ester hydrolysis is essential in digestion (catalyzed by lipase) and soap-making.
- Acid and base hydrolysis mechanisms differ in intermediates and leaving groups.
Hydrolysis in Synthesis
- Acid-catalyzed hydrolysis is used in penicillin synthesis to convert esters or amides to carboxylic acids or amines.
- Protecting groups (like tert-butyl esters) can be added and later removed by hydrolysis during synthesis.
Key Terms & Definitions
- Ester — a compound formed from an acid and an alcohol, containing the –COOR group.
- Carboxylic Acid Derivative — compounds derived from carboxylic acids (acid chlorides, anhydrides, esters, amides).
- Inductive Effect — electron withdrawal through sigma bonds by electronegative atoms.
- Resonance Effect — delocalization of electrons that stabilizes molecules.
- Nucleophilic Acyl Substitution — reaction where a nucleophile replaces a leaving group on an acyl compound.
- Hydrolysis — reaction with water that breaks bonds, converting derivatives to carboxylic acids/salts.
- Saponification — base-catalyzed hydrolysis of esters to make soap.
Action Items / Next Steps
- Review mechanisms of acid- and base-catalyzed hydrolysis for esters and amides.
- Prepare for the next lecture on interconversion of carboxylic acid derivatives.