Preparation of Amines

Full Notes

Amines can be prepared using a variety of methods and the choice of method used is based on the desired product and functional group compatibility.

Reduction of Nitro Compounds

Nitro compounds are reduced to amines using:

Catalytic hydrogenation

Uses H₂ gas in the presence of Ni, Pd, or Pt in ethanol.

Metals in acidic medium

Common metals include Sn + HCl and Fe + HCl.

Both aromatic and aliphatic nitro compounds can be reduced to the corresponding amines.

Iron/HCl is preferred industrially as FeCl₂ hydrolyses to regenerate HCl, reducing the need for excess acid.

Example: C₆H₅NO₂ + 6[H] → C₆H₅NH₂ + 2H₂O
Used commonly for preparing aromatic amines like aniline.

Ammonolysis of Alkyl Halides

Ammonolysis is the nucleophilic substitution of alkyl or benzyl halides by ammonia (NH₃).

• Carried out in a sealed tube at 373 K.
• The halogen is replaced by an amino group (–NH₂).
• This yields primary amines (R–NH₂) initially.
• The primary amine can further react with more alkyl halide to give:
  • Secondary amine (R₂NH)
  • Tertiary amine (R₃N)
  • Quaternary ammonium salt (R₄N⁺X⁻)

Free amine recovery: The substituted ammonium salt can be treated with NaOH to liberate the free amine:

R–NH₃⁺X⁻ + NaOH → R–NH₂ + H₂O + NaX

Reaction Mechanisms and Steps:

Amines can act as nucleophiles (electron pair donors) due to the lone pair of electrons on the nitrogen atom, which can attack electron-deficient species, such as a carbon atom with a partially positive charge. Amines react with halogenoalkanes in a series of nucleophilic substitution steps to form primary, secondary and tertiary amines.

Primary Amine Formation:

Secondary Amine Formation:
Previously formed primary amine can now go on and react as a nucleophile with original halogenoalkane reactants.

Tertiary Amine Formation:
Previously formed secondary amine can go on and react as a nucleophile with original halogenoalkane reactants.

Quaternary Ammonium Salt Formation:
Previously formed tertiary amine can go on and react as a nucleophile with original halogenoalkane reactant however this time forms a positively charged ion – there is no H⁺ ion it can lose to become neutral. This produces an alkyl ammonium salt.

Reduction of Nitriles

Nitriles (–CN) can be reduced to primary amines (–CH₂NH₂).

Using LiAlH₄ in dry ether (laboratory method):

R–CN + 4[H] → R–CH₂NH₂

Catalytic hydrogenation (industrial method):

• Reagent: H₂ gas + Nickel catalyst
• Conditions: High pressure and temperature
• Advantage: Produces only primary amines (unlike halogenoalkane method).

Note: Chain extended by one carbon, meaning this is a useful process to extend cabron chain length.

Reduction of Amides

Amides can be reduced to corresponding amines using lithium aluminium hydride as a reducing agent.

R–CONH₂ + 4[H] → R–CH₂NH₂ + H₂O

Applicable to both aliphatic and aromatic amides.

Gabriel Phthalimide Synthesis

The Gabriel Phthalimide Synthesis method is used to prepare primary amines, particularly alkyl amines.

• Phthalimide is treated with ethanolic KOH to form potassium phthalimide, a nucleophile.
• It then undergoes nucleophilic substitution with an alkyl halide (R–X) to give N-alkylphthalimide.
• Alkaline hydrolysis of N-alkylphthalimide using NaOH(aq) gives:
  • Primary amine (R–NH₂)
  • Sodium salts of phthalic acid

Hoffmann Bromamide Degradation Reaction

The Hoffmann Bromamide Degradation method is used for preparing primary amines from amides.

• Amide is treated with Br₂ and NaOH (aqueous or ethanolic).
• The reaction involves migration of an alkyl or aryl group from the carbonyl carbon to the nitrogen atom.
• The resulting amine contains one carbon less than the original amide.

R–CONH₂ + Br₂ + 4NaOH ⟶ R–NH₂ + Na₂CO₃ + 2NaBr + 2H₂O

This reaction is useful for:

• Shortening carbon chains
• Converting higher amides to smaller amines

Summary

• Nitro compounds reduce to amines by catalytic hydrogenation or metals in acid.
• Ammonolysis of alkyl halides gives a series from primary to quaternary products.
• Nitriles and amides reduce with LiAlH₄ or H₂/Ni to primary amines.
• Gabriel synthesis prepares pure primary alkyl amines and not aryl amines.
• Hoffmann degradation gives a primary amine with one fewer carbon atom.