Preparation of Amines

1. Reduction of nitro compounds:

Reactants: Nitro compounds

Reagent: H₂ in the presence of finely divided nickel, palladium or platinum

Product: Amines

Reactants: Nitro compounds

Reagent: Metals in acidic medium. Reduction with iron scrap and hydrochloric acid is preferred because FeCl₂ formed gets hydrolysed to release hydrochloric acid during the reaction. Thus, only a small amount of hydrochloric acid is required to initiate the reaction.

Product: Amines

This method cannot be used when the molecule also contains some other easily hydrogenated group, such as a Carbon carbon double bond.

2. Ammonolysis of alkyl halides:

Reactants: alkyl or benzyl halide

Reagent: ethanolic solution of ammonia

Mechanism: nucleophilic substitution reaction

Product: Amines

CH₃CH₂CH₂Br + NH₃ → CH₃CH₂CH₂NH₂ + HBr

This process of cleavage of the C–X bond by ammonia molecule is known as ammonolysis.

The primary amine thus obtained behaves as a nucleophile and can further react with alkyl halide to form secondary and tertiary amines, and finally quaternary ammonium salt.

The free amine can be obtained from the ammonium salt by treatment with a strong base:

R - NH⁺₃X⁻ + NaOH → R - NH₂ + H₂O + NaX⁻

The order of reactivity of halides with amines is RI > RBr >RCl.

3. Reduction of nitriles: This reaction is used for ascent of amine series, i.e. for preparation of amines containing one carbon atom more than the starting nitrile.

Reactants: Nitriles

Reagent: lithium aluminium hydride (LiAlH⁴)

Reaction: Reduction

Products: Amines

Reactants: Nitriles

Reagent: H² in presence of catalyst Ni

Reaction: Reduction

Product: Amines

4. Reduction of amides:

Reactants: Amides

Reagent: Lithium aluminium hydride (LiAlH₄)

Reaction: Reduction

Product: Amines

Reactants: Amides

Reagent: mixture of base and bromine (KOH + Br₂)

Product: Hofmann Bromamide reaction.

Product: Amines

The reaction is as follows, RCONH₂ + Br₂ + 4KOH → RNH₂ + K₂CO₃ + 2KBr + 2H₂O

Here, the amine formed has one carbon less than that of the corresponding amide. Due to the loss of carbon atom, this reaction is also called as Hofmann degradation of amides.

Base abstracts an acidic N-H proton, yielding an anion.

The anion reacts with bromine in an α-substitution reaction to give an N-bromoamide.

Base abstraction of the remaining amide proton gives a bromoamide anion.

The bromoamide anion rearranges as the R group attached to the carbonyl carbon migrates to nitrogen at the same time the bromide ion leaves, giving n isocyanate.

The isocyanate adds water in a nucleophilic addition step to yield a carbamic acid (aka urethane).

The carbamic acid spontaneously loses CO₂, yielding the amine product.

Apart from this, amides can be dehydrated by P₂O₅ to their corresponding nitriles and nitriles can then be reduced.

By this method you are retaining the number of carbon atoms in both amide and the amine

5. Gabriel phthalimide synthesis:

Reactants: Pthalimide and alkyl halide

Reagent: Ethanolic potassium hydroxide  

Product: Primary amine

Phthalimide on treatment with ethanolic potassium hydroxide forms potassium salt of phthalimide

Phthalimide on heating with alkyl halide followed by alkaline hydrolysis produces the corresponding primary amine.

Aromatic primary amines cannot be prepared by this method because aryl halides do not undergo nucleophilic substitution with the anion formed by phthalimide.

6. Schmidt reaction (IIT):

Reactants: Hydrozoic acid and carboxylic acid

Reagent: Sulphuric acid

Product: Amines

7. Curtius Reaction (IIT):

Reactants: Acid chloride and sodium azides

Reagent: Heat and water

Product: Amines

The isocyanate formed by reaction of acid chloride with sodium azides is decomposed with treatment of water and amines are obtained.