In the world of organic synthesis, certain reactions are considered “workhorses.” These transformations help chemists reduce, oxidize, rearrange, or condense molecules to create complex drugs from simple starting materials. From painkillers to antibiotics, many pharmaceuticals rely on a small set of powerful reactions that shape molecular structure with precision.
UNIT 5 highlights these synthetically important reactions, giving students practical tools for designing and modifying drug molecules in laboratories and industry.
Reduction Reactions: Turning Carbonyls into Alcohols and Hydrocarbons
Reduction reactions play a crucial role in modifying functional groups and adjusting molecular activity.
Metal Hydride Reduction (NaBH₄ and LiAlH₄)
Sodium Borohydride (NaBH₄)
A mild reducing agent, sodium borohydride selectively reduces:
- Aldehydes → alcohols
- Ketones → alcohols
Lithium Aluminium Hydride (LiAlH₄)
A stronger reagent that reduces:
- Aldehydes and ketones
- Esters
- Carboxylic acids
- Amides
Applications
- Synthesis of alcohol intermediates
- Drug modification
- Preparation of fine chemicals
These reagents are widely used because they provide clean and predictable results.
Clemmensen Reduction
Principle
Carbonyl groups are reduced to hydrocarbons using zinc amalgam and concentrated hydrochloric acid.
Key Features
- Acidic medium
- Converts ketones/aldehydes to alkanes
Uses
Useful when acid-stable substrates are present. Often applied in aromatic ketone reductions.
Wolff–Kishner Reduction
Principle
This method reduces carbonyl groups to methylene groups using hydrazine in basic medium.
Advantages
- Operates under basic conditions
- Suitable for acid-sensitive compounds
Importance
Complements Clemmensen reduction, giving chemists flexibility based on reaction conditions.
Birch Reduction
Principle
Partial reduction of aromatic rings using alkali metals in liquid ammonia.
Outcome
Converts benzene rings into non-aromatic dienes.
Applications
- Modifying aromatic systems
- Steroid synthesis
- Medicinal chemistry intermediates
Birch reduction is especially valuable for selective ring modification.
Oxidation Reactions: Controlled Functional Group Transformation
Oxidation reactions introduce or enhance oxygen-containing groups in molecules.
Oppenauer Oxidation
Principle
Secondary alcohols are oxidized to ketones using aluminium alkoxide in the presence of a ketone.
Characteristics
- Mild conditions
- Selective oxidation
Uses
Common in steroid and pharmaceutical synthesis where delicate structures must remain intact.
Dakin Reaction
Principle
Ortho- or para-hydroxy aromatic aldehydes/ketones react with hydrogen peroxide in alkaline medium to form phenols.
Applications
- Preparation of substituted phenols
- Medicinal intermediates
- Fine chemical synthesis
This reaction is particularly useful in aromatic chemistry.
Rearrangement Reactions: Structural Reorganization
Rearrangements change the skeleton of molecules, often producing valuable amine derivatives.
Beckmann Rearrangement
Principle
Oximes convert into amides under acidic conditions.
Example
Cyclohexanone oxime → caprolactam (nylon precursor)
Pharmaceutical Importance
Forms lactams and amide-containing drugs, common in antibiotics and analgesics.
Schmidt Rearrangement
Principle
Carboxylic acids or ketones react with hydrazoic acid to form amines or amides with nitrogen insertion.
Applications
- Synthesis of amines
- Preparation of lactams
- Structural modification
Useful for expanding or modifying carbon chains.
Condensation Reactions: Building Larger Molecules
Claisen–Schmidt Condensation
Principle
An aldol condensation between aromatic aldehydes and ketones in the presence of base.
Products
α,β-unsaturated ketones (chalcones)
Importance
- Synthesis of flavonoids
- Anti-inflammatory agents
- Antimicrobial compounds
This reaction forms carbon–carbon bonds, making it central to organic synthesis.
Why These Reactions Matter in Pharmaceutical Chemistry
These transformations allow chemists to:
- Modify functional groups
- Control drug activity
- Improve solubility
- Enhance stability
- Build complex molecules efficiently
Without these classic reactions, modern drug design would be slow and impractical.
Quick Comparison Table
| Reaction | Purpose | Medium |
|---|---|---|
| NaBH₄ | Mild reduction | Neutral |
| LiAlH₄ | Strong reduction | Anhydrous |
| Clemmensen | Carbonyl → alkane | Acidic |
| Wolff–Kishner | Carbonyl → alkane | Basic |
| Birch | Aromatic reduction | Ammonia |
| Oppenauer | Alcohol oxidation | Mild |
| Beckmann | Oxime → amide | Acidic |
| Claisen–Schmidt | C–C bond formation | Basic |