Amine preparation

NH₂

Methods of Preparation of Amines — Easy & Exam-Focused

Clear Class 12 notes, JEE/NEET friendly — nitro reduction, Gabriel, Hoffmann, reductive amination and more.

Nitro reduction Ammonolysis Gabriel Hoffmann Grignard & others

Amines are organic derivatives of ammonia (NH₃) in which one or more hydrogen atoms are replaced by alkyl or aryl groups. They are classified as primary (1°), secondary (2°), and tertiary (3°). Below are the most important laboratory and industrial methods for preparing amines — written simply for students and teachers.

1. Reduction of Nitro Compounds (→ Primary Amines)

This is the most common method to prepare primary amines from nitro compounds (aromatic or aliphatic). Nitro groups are reduced to amino groups using chemical or catalytic hydrogenation.

R–NO₂ → R–NH₂
Common reagents: Sn/HCl, Fe/HCl, H₂/Ni, LiAlH₄.

2. Ammonolysis of Alkyl Halides (R–X + NH₃)

Alkyl halides react with ammonia to produce amines. This method can give a mixture of 1°, 2°, 3° amines and quaternary ammonium salts.

Note: To obtain pure primary amines from alkyl halides use Gabriel phthalimide synthesis.

3. Gabriel Phthalimide Synthesis (Pure 1° Amines)

A reliable method for preparing pure primary amines (except aromatic amines) without producing 2° or 3° products.

Phthalimide → (alkylation) → N-alkyl phthalimide → (hydrolysis) → R–NH₂

4. Reduction of Amides

Amides reduce to amines using strong hydride reagents like LiAlH₄. This gives excellent yields of primary amines.

5. Reduction of Nitriles

Nitriles (R–CN) reduce to primary amines (R–CH₂NH₂). This method is useful for chain-extension by one carbon.

6. Hoffmann Bromamide Degradation (One-Carbon Shortening)

Hoffmann reaction converts amides to primary amines with one less carbon atom — an important degradation reaction in organic synthesis.

R–CONH₂ + Br₂ + NaOH → R–NH₂ + CO₂

7. Curtius Rearrangement

Acyl azides upon heating rearrange to isocyanates and then hydrolyze to primary amines with loss of CO₂. Widely used in medicinal chemistry.

8. Reductive Amination (Most Versatile Industrial Route)

Reductive amination converts aldehydes/ketones to amines via an imine intermediate. It is highly useful industrially and allows selective formation of 1°, 2°, or 3° amines.

Carbonyl + NH₃ → Imine → (H₂/catalyst or NaBH₃CN) → Amine

9. Other Methods (Imines, Oximes, Isocyanides)

Imines and oximes can be reduced to amines; isocyanide hydrolysis also yields primary amines. These are useful in multi-step syntheses and drug design.

Quick Comparison

• Most selective for 1° amines: Gabriel synthesis, Hoffmann, reduction of amides
• Industrial workhorse: Reductive amination, catalytic hydrogenation of nitro compounds
• Chain extension: Reduction of nitriles

FAQs

Q. Which method gives only primary amines? Gabriel phthalimide synthesis and Hoffmann degradation give predominantly primary amines.

Q. How does reductive amination help in industry? It is versatile and selective — used to prepare a wide range of amines from carbonyl compounds with controlled substitution.

Q. Can we prepare aromatic amines using nitrile reduction? Yes — aryl nitriles can be reduced to aryl methylamines, and aromatic nitro compounds are commonly reduced to anilines.