m pharma chemistry rearrangement ppt.pptx

m pharma chemistry

1. Rearrangement Reactions Pharmaceutical Organic Chemistry (M.Pharm) Submitted by Aparna kumari

2. Introduction • Rearrangement Reaction: shifting of atoms/groups within molecule. • Produces isomers with different properties. • Important in drug synthesis, intermediates, natural products.

3. Classification of Rearrangement Reactions 1. Anionic rearrangements → Benzilic acid rearrangement 2. Cationic rearrangements → Pinacol–Pinacolone 3. Radical rearrangements → Wagner–Meerwein 4. Pericyclic rearrangements → Claisen, Cope

4. Beckmann Rearrangement • Oximes → Amides (H2SO4, PCl5, SOCl2) • Mechanism: Protonation → group migration → amide • Pharma use: Paracetamol, β-lactams (antibiotics)

5. Hofmann Rearrangement • Primary amides → Primary amines (Br2 + NaOH) • Loss of –CO group • Pharma use: Intermediates for anesthetics, antihistamines

6. Curtius & Claisen Rearrangements Curtius: Acyl azides → Isocyanates → Amines • Used in amino acid, drug intermediate synthesis Claisen: Allyl vinyl ethers → γ,δ-unsaturated carbonyls • Used in flavonoid and natural product synthesis

7. Lossen rearrangement:- The Lossen rearrangement is the thermal decomposition of an O-acyl hydroxamic acid (or its derivatives) to give an isocyanate, which can then be hydrolyzed to form a primary amine.

8. Pinacol & Wagner–Meerwein Rearrangements Pinacol–Pinacolone: Diols → Ketones (via carbocation) • Used in steroid, sedative synthesis Wagner–Meerwein: Carbocation rearrangements • Used in terpenes, steroids

9. Other Named Rearrangements • Benzilic acid rearrangement → CNS drugs • Fries rearrangement → NSAID synthesis • Favorskii rearrangement → Corticosteroids • Neber rearrangement → Aminoketone drug precursors