AMINES

Preparation Reactions for Amines

Preparation of mixture of Amines from Ammonia and Alkyl Halide
(Preparation of R4NX)

Preparation of mixture of Amines from Ammonia and Alkyl Halide
(Preparation of R4NX)

R-X + NH3 → R-NH2 (Primary Amine) + H-X (+ R-X) → R-R-NH (Secondary Anime) + H-X (+ R-X) → R-R-R-NH (Tertiary Amine) + H-X (+ R-X) → R-R-R-R-N-X (Quaternary Ammonium Salt)

Reagents for reduction of Nitro Group to form Amines

1. Sn + HCl

2. Fe + HCl (gives the most yield)

3. H2 in the presence of Ni catalyst

These reagents help in removing -NO2 and replace it with -NH2 from an organic compound.

Reagents for reduction of Cyanides to form Amines

1. H2 in the presence of Ni/Pt/Pd

2. LiAlH4

3. Na(Hg) in the presence of an alcohol (R-OH)

Triple bonds of CN break to form one single bond and hydrogen is substituted to each bond, forming CH2-NH2

Reagents for reduction of Isocyanides to form Amines

1. H2 in the presence of Ni/Pt/Pd

2. LiAlH4

Triple bonds of CN break to form double bonds and hydrogen is substituted to the bond, forming NH=CH2

Reagents for reduction of Amides to form Amines

1. LiAlH4

Amides are Ar/R-C=O-NH2

R-C(=O)-NH2 → R-CH2-NH2

Ar-C(=O)-NH2 → Ar-CH2-NH2

Gabriel Phthalimide Synthesis

Mechanism:

1. Deprotonation of Phthalimide:

Potassium hydroxide (KOH) deprotonates the phthalimide, creating a nucleophilic imide ion. The imide ion is stabilized by resonance due to the presence of two carbonyl groups.

2. Alkylation:

The nucleophilic imide ion attacks the electrophilic carbon of the alkyl halide, displacing the halogen (X) and forming an N-alkyl phthalimide.

3. Hydrolysis:

The N-alkyl phthalimide undergoes base-catalyzed hydrolysis, where the hydroxide ion attacks the carbon-nitrogen bond. This leads to the cleavage of the N-alkyl phthalimide and the formation of the primary amine and a phthalate ion.

Structure of Imide

1 N attached to 2 (or more) primary or secondary R’s which are doubly bonded with their O’s.

Structure of Imine

1 N (with a lone pair) doubly bonded to a secondary C and singly bonded to an R

Hoffmann Bromamide Degradation

The Hoffmann Bromamide Degradation is a chemical reaction used to convert primary amides into primary amines with the loss of one carbon atom (Step Down Reaction)

1. Formation of N-Bromoamide:

   The primary amide reacts with bromine in the presence of a strong base, such as sodium hydroxide (NaOH), resulting in the formation of an N-bromoamide.

2. Deprotonation and Rearrangement:

   The strong base deprotonates the N-bromoamide, generating an anion. This anion then undergoes rearrangement, where the alkyl or aryl group attached to the carbonyl carbon migrates to the nitrogen, forming an isocyanate intermediate. During this rearrangement, a bromide ion is expelled.

3. Hydrolysis of Isocyanate:

   The isocyanate intermediate is then hydrolyzed in the presence of water or aqueous base, leading to the formation of a primary amine and the release of carbon dioxide (CO₂).

The overall reaction can be summarized as follows:

RCONH₂ (primary amide) + Br₂ + 4 NaOH → RNH₂ (primary amine) + Na₂CO₃ + 2 NaBr + 2 H₂O

Acylation Reaction of Amines

R-NH2 + R-C=O-Cl → R-NH-C=O-R + HCl

Carbyl Amine Test

R-NH2 + CHCl3 + KOH → R-NC

(Foul smell of isocyanide indicates presence of 1 degree Amine)

Formation of Carbene (CCl2) as an intermediate due to alpha elimination occurs.

Reagents for reactions of Amines with Nitrous Acids (HNO2)

Reagents:

1. HNO2

2. NaNO2 + HCl → NaCl + HNO2

Reactions of 1 degree Aliphatic Amines with Nitrous Acids

R-NH2 + HNO2 → R-N2-Cl (Diazonium Salt) → R+ (Carbocation - rearrangement may occur) + H2O → R-OH (Alcohol)

Reactions of 1 degree Aromatic Amines with Nitrous Acids

Ph-NH2 + NaNO2 + HCl → Ph-N2-Cl (Benzene Diazonium Chloride) + H2O → Phenol