Aliphatic amines undergo a wide range of chemical reactions, reflecting their versatile nature in organic chemistry.
These reactions are primarily due to the nucleophilic character of the nitrogen atom, which carries a lone pair of electrons.
Below are some of the important chemical reactions involving aliphatic amines:
1. Alkylation
Aliphatic amines can react with alkyl halides to form secondary and tertiary amines, or even quaternary ammonium salts, in a reaction known as alkylation.
This process illustrates the nucleophilic substitution mechanism where the lone pair of electrons on the nitrogen atom attacks an electrophilic carbon in the alkyl halide.
RNH2+R′X→RNHR′+HX
R and ′R′ represent alkyl groups,
X is a halide ion.
The reaction can continue, leading to over-alkylation if not carefully controlled.
2. Acylation
Amines can undergo acylation to form amides by reacting with acid chlorides, anhydrides, or esters.
This reaction involves the nucleophilic attack of the amine on the carbonyl carbon of the acylating agent.
RNH2+R′COCl→RNHCOR′+HCl
Acylation is a useful way to protect the amine functionality during synthetic operations.
3. Nitrosation
Primary aliphatic amines react with nitrous acid (generated in situ from sodium nitrite and hydrochloric acid) to form diazonium salts at 0 to 5°C.
The diazonium salts are key intermediates for various synthetic transformations, including azo coupling and Sandmeyer reactions.
RNH2+HNO2→[R−N2]++2H2O
4. Hoffman Elimination
When a quaternary ammonium salt (obtained from an amine through exhaustive alkylation) is treated with a strong base, it undergoes Hoffman elimination to give an alkene.
This reaction involves the elimination of a molecule of water or halogen acid and is useful for synthesizing alkenes with one less carbon atom than the original amine.
R4N+X−+OH−→R3N+H2O+RX
5. Reaction with Hinsberg’s Reagent
Amines react with benzene sulfonyl chloride (Hinsberg's reagent) in the presence of an alkali to form sulfonamides.
This reaction distinguishes primary, secondary, and tertiary amines:
Primary amines form N-alkylsulfonamides, which are soluble in alkali.
Secondary amines form N,N-dialkylsulfonamides, insoluble in alkali.
Tertiary amines do not react due to the lack of a hydrogen atom on nitrogen.
6. Gabriel Phthalimide Synthesis
While more of a synthesis method for amines, it's worth mentioning that amines can also be used in the Gabriel synthesis for generating primary amines.
This involves the reaction of phthalimide with an alkyl halide, followed by hydrolysis.
7. Nucleophilic Substitution Reactions
Primary and secondary amines can act as nucleophiles in substitution reactions with various electrophiles, including carbon, sulfur, and nitrogen centers.
This allows for the formation of a wide range of derivatives and is fundamental to building complex molecules in organic synthesis.
8. Electrophilic Aromatic Substitution
Aromatic amines (aniline and its derivatives) undergo electrophilic aromatic substitution reactions more readily than benzene, due to the electron-donating effect of the amino group.
This leads to products where substitution often occurs at the ortho and para positions relative to the amino group.