Carboxylic Acids and Derivatives

Introduction

• Comprehensive survey of carboxylic acids and derivatives.

Carboxylic Acids (COOH) and Derivatives

• Carboxylic Acid: Carbonyl group (CO) next to OH group.
• Acid Chloride: Replace OH in carboxylic acid with chlorine (Cl).
• Acid Anhydride: Two carbonyl groups (CO) connected by an oxygen (O) with alkyl groups on both sides.
• Ester: Carbonyl group (CO) connected to oxygen (O) and an alkyl group (R) instead of a proton.
• Amide: Carbonyl group (CO) connected to nitrogen (N); can be primary (NH2), secondary (NHR), or tertiary (NR2).

Naturally Occurring Carboxylic Acids

• Acetic Acid: Gives vinegar its sour taste.
• Butyric Acid: Found in dairy products, contributes to buttery taste.
• Caproic Acid: Found in goat cheese.
• Palmitic Acid: Long-chain fatty acid, component of phospholipids, critical for biological membranes.

Properties of Carboxylic Acids

• Acidity: Weakly acidic, e.g., acetic acid has a pKa of 4.8.
• Enhancing Acidity: Adding electron-withdrawing groups increases acidity, e.g., trifluoroacetic acid with pKa of 0.25.
• Conjugate Base Stability: Stabilizing the negative charge increases acidity.

Reactions and Applications

Acid Chloride Formation

• React carboxylic acid with thionyl chloride: Evolves HCl and SO2 to form acid chloride.

Ester Formation

• From Acid Chloride: Acid chloride reacts with alcohol, intermediate forms and leads to ester by kicking off Cl.
• Hydrolysis: Susceptible to hydrolysis, can revert to carboxylic acid.

Anhydride Chemistry

• Symmetrical and Asymmetrical Anhydrides: React with nucleophiles, can attack either carbonyl to form different products.
• Leaving Groups: Carboxylate anions are stable leaving groups due to resonance stabilization.

Amide Formation

• Schotten-Baumann Amidation: Acid chloride reacts with amine in organic solvent and NaOH to form amides.

Ketone Synthesis

• Weinreb Amide: Reacts with Grignard reagent; forms stable chelate intermediate and then ketone after protonation.
• Amide to Nitrile: Amide reacts with thionyl chloride to form nitrile, then reacts with Grignard reagent to form ketone.

Summary

• Reviewed carboxylic acids and derivatives: acid chlorides, anhydrides, esters, amides.
• Applications in synthetic chemistry: formation of esters, nitriles, and ketones from carboxylic acid derivatives.