Organic Chemistry: Carboxylic Acids, Amines, and Heterocycles

Posted on Jun 23, 2025 in Biotechnology

Unit 1: Carboxylic Acids and Their Derivatives

Preparation of Carboxylic Acids

Oxidation Reactions

  • Primary alcohols → Carboxylic acids (using KMnO4, CrO3, etc.)
  • Aldehydes → Carboxylic acids
  • Ketones (via haloform reaction in methyl ketones)

Ester Hydrolysis

  • Acidic hydrolysis: RCOOR’ + H2O → RCOOH + R’OH
  • Alkaline hydrolysis (saponification): RCOOR’ + OH− → RCOO− + R’OH

Important Reactions of Carboxylic Acids

Hell-Volhard-Zelinsky Reaction

  • α-halogenation of carboxylic acids using Br2 + PBr3
  • Mechanism: enol formation → electrophilic halogenation

Carboxylic Acid Derivatives

Preparation from Carboxylic Acids

  • Acid Chlorides: RCOOH + SOCl2
  • Anhydrides: RCOOH + RCOCl
  • Esters: Fischer esterification (RCOOH + ROH + H+)
  • Amides: RCOCl + NH3

Interconversion of Derivatives

  • Acid chlorides → esters/amides/anhydrides via nucleophilic acyl substitution

Key Reactions & Mechanisms

Claisen Condensation

  • Two esters (or ester + ketone) form β-keto ester via enolate ion attack

Reformatsky Reaction

  • α-haloester + Zn + carbonyl → β-hydroxy ester

Perkin Condensation

  • Aromatic aldehyde + acid anhydride (base catalyst) → α,β-unsaturated acid

Active Methylene Compounds

Keto-Enol Tautomerism

  • Dynamic equilibrium between keto and enol forms

Ethyl Acetoacetate

  • Preparation: Claisen condensation of ethyl acetate
  • Uses: Synthesis of ketones, acids, amino acids via alkylation and hydrolysis

Unit 2: Amines

Preparation of Amines

  • From alkyl halides (via ammonia)
  • Gabriel Phthalimide Synthesis (for primary amines)
  • Hoffmann Bromamide Degradation: RCONH2 + Br2 + NaOH → RNH2

Reactions of Amines

Hoffmann vs. Saytzeff Elimination

  • Hoffmann: Less substituted alkene (due to bulky leaving group)
  • Saytzeff: More substituted alkene

Carbylamine Test

  • Primary amine + chloroform + base → isocyanide (foul smell)

Hinsberg Test

  • Distinguishes primary, secondary, and tertiary amines via sulfonamide derivatives

Reaction with Nitrous Acid (HNO2)

  • Primary amines: forms alcohols
  • Secondary amines: nitrosoamines (yellow oily)
  • Tertiary amines: no reaction

Schotten-Baumann Reaction

  • Amines + acid chloride → amides (under basic conditions)

Electrophilic Substitution in Aniline

  • Nitration, Bromination, Sulphonation
  • Activating –NH2 directs to ortho/para positions
  • Often requires protection of –NH2 as acetamide

Basicity of Amines

  • Influenced by:
    • Inductive effect
    • Solvation
    • Resonance (aromatic amines less basic due to delocalization)

Diazonium Salts

Preparation of Diazonium Salts

  • ArNH2 + HNO2 (from NaNO2 + HCl) at 0–5°C → ArN2+Cl−

Reactions of Diazonium Salts

  • ArN2+ → ArOH (phenol)
  • ArN2+ → ArH (reduction)
  • ArN2+ → Azo dyes (coupling with activated aromatic compounds)

Unit 3: Heterocyclic Compounds

Introduction to Heterocyclic Compounds

  • Cyclic compounds with heteroatoms (N, O, S)
  • Classified as 5-membered (furan, pyrrole, thiophene) and 6-membered (pyridine)

Structures & Properties

  • Furan: 5-membered, O atom, aromatic
  • Pyrrole: NH group, aromatic (lone pair contributes to ring)
  • Thiophene: Sulfur in ring, aromatic
  • Pyridine: 6-membered, basic (N atom not part of aromatic sextet)

Electrophilic and Nucleophilic Substitution

Pyrrole, Furan, Thiophene

  • Undergo Electrophilic Aromatic Substitution (EAS) at α-position (more reactive than benzene)

Pyridine

  • EAS at meta position (electron-deficient ring)
  • Nucleophilic Aromatic Substitution (NAS) at ortho/para positions (more reactive towards nucleophiles)