Carboxylic Acid Derivatives Overview

Carboxylic Acid Derivatives

• Carboxylic acids have a general structure with a carbonyl group (C=O) and a hydroxyl group (OH).
• Acyl group: The carbon chain attached to the carbonyl group
• Electronegative atom (Z): The atom bonded to the carbonyl carbon in derivatives, impacting acid/base properties
• Common derivatives include: acid chlorides, anhydrides, esters, amides, and nitriles.

Types of Carboxylic Acid Derivatives

• Acid Chlorides:
  • General structure: R-C(=O)-Cl
  • React readily with nucleophiles, forming substitution products.
  • Often form HCl as a byproduct which must be neutralized.
• Anhydrides:
  • General structure: R-C(=O)-O-C(=O)-R
  • Formed from the dehydration of two carboxylic acid molecules.
  • React with nucleophiles, resulting in the carbonyl group of the anhydride breaking the bond
  • The nucleophile attacks one carbonyl group and the carbonyl from the other part is the leaving group
• Esters:
  • General structure: R-C(=O)-OR'
  • Formed by the condensation reaction of a carboxylic acid with an alcohol.
  • Hydrolysis can be performed by acid or base, to form a carboxyl and alcohol.
• Amides:
  • General structure: R-C(=O)-NR'R"
  • Formed by the reaction of a carboxylic acid with ammonia or amines
  • Exist in two tautomeric forms that interconvert, with the amide form usually being more stable.
• Nitriles:
  • General structure: R-C≡N
  • Prepared by SN2 reactions of unhindered methyl and 1° alkyl halides with CN.
  • Involve hydrolysis reactions to form carboxylic acids.

Reactions of Carboxylic Acid Derivatives

• Nucleophilic Acyl Substitution:
  • Characterizes the reactions of carboxylic acid derivatives
  • Involves the nucleophilic attack at the carbonyl carbon, following by loss of the leaving group.
  • Oxygen nucleophiles: Can react to form anhydrides, carboxylic acids or esters
  • Nitrogen nucleophiles: Can react to form amides.

Anhydrides

• Types of anhydrides:
  • Symmetrical Anhydride: "Two R Groups are the same."
  • Mixed Anhydride: "Two R Groups are different."
  • Cyclic Anhydride: "Cyclic" structures.

Amides

• Types of amides:
  • Primary Amide: One C-N bond.
  • Secondary Amide: Two C-N bonds.
  • Tertiary Amide: Three C-N bonds.

Cyclic Esters and Amides

• Lactones: Cyclic esters.
• Lactams: Cyclic amides.

Structure and Bonding

• The carbonyl group (C=O) is sp2 hybridized, making it trigonal planar
• The electronegative oxygen atom polarizes the carbonyl group, making the carbonyl carbon electrophilic
• Three resonance structures stabilize carboxylic acid derivatives by delocalizing electron density.

Stability of Carboxylic Acid Derivatives

• Stability increases with increasing basicity of Z

Acid Chlorides Reactions

• Acid chlorides readily react with nucleophiles to form nucleophilic substitution products.
• A weak base (like pyridine) is usually required to neutralize the byproduct strong acid HCl.

Nomenclature

• Specific names and abbreviations exist for different types of carboxylic acid derivatives and nitriles.

IR Spectroscopy

• Provides characteristic absorption frequencies for carbonyl groups. Frequency data varies by derivative type

Acid-Catalyzed Hydrolysis

• Mechanisms for converting esters and amides into carboxylic acid involve protonation and loss of an OH or NH2 group.

Base-Promoted Hydrolysis (Saponification)

• Base-promoted hydrolysis results in the formation of a carboxylate anion.

Reactions of Nitriles

• Hydrolysis reactions form carboxylic acids or carboxylate anions
• Reduction with LiAlH4 forms a primary amine.
• Reduction with DIBAL-H forms an aldehyde.
• Organometallic reagents add to the nitrile group resulting in ketones.

Carboxylic Acid Reactions

• Carboxylic acids behave as acids in water, neutralizing bases to form carboxylate salts.
• Other reactions form functional derivatives from the carboxylic acid.

Resonance Stabilization of Carboxylates

• Resonance stabilization plays a crucial role in the equilibrium of the reaction.

Summary

• Carboxylic acid derivatives, such as acid chlorides, anhydrides, esters, amides, and nitriles, exhibit distinct properties and reactivity patterns.