Chapter 21 (Amines)

A Nitrogen-based compound possessing one/two/three alkyl or aryl groups (bonded to the Nitrogen). The reactivity of Amines differs greatly from other Nitrogen-containing compounds (i.e. Enamines, Amides, Imines, Iminiums, Ammoniums).

A compound possessing an amino group adjacent to an alkene group.

A compound possessing an amino group adjacent to a carbonyl group. The Nitrogen lone-pair electrons are in conjugation with the π electrons of the carbonyl group.

A compound possessing a Carbon-Nitrogen double bond.

A cationic compound possessing a Carbon-Nitrogen double bond and a quadruple-substituted Nitrogen.

A cationic Nitrogen compound with four alkyl/aryl substituents (bonded to the Nitrogen).

—NR2 R = Alkyl/Aryl/Hydrogen

Tetrahedral Geometry (sp3-Hybridized Nitrogen)

Tetrahedral Geometry (sp3-Hybridized Nitrogen) The aryl amine displays a tetrahedral-like geometry despite the weak conjugation between the Nitrogen lone pair and the aromatic π electrons. (This conjugation is significantly weaker than the conjugation present in amides, so the aryl amine is tetrahedral-like overall.)

Planar Geometry (sp2-Hybridized Nitrogen) The planar geometry of amides is caused by the strong conjugation between the Nitrogen lone pair and the carbonyl π electrons.

The Nitrogen lone-pair electrons of alkyl amines are better able to undergo nucleophilic attack due to the absence of conjugation to delocalize the electrons. The Nitrogen lone-pair electrons of aryl amines are in conjugation with the aromatic π electrons, so they are less nucleophilic/reactive.

β-Carbon Serves as Nucleophile

Carbonyl Carbon Serves as Electrophile The Nitrogen lone pair cannot serve as the nucleophile.

Imine Carbon Serves as Electrophile Imine Carbon = C=N

Hydrogen Serves as Acid Acid-Base Reactions

Iminium Carbon Serves as Electrophile Imine Carbon = C=N+

An amine is chiral if it possess three unique substituents (bonded to the Nitrogen atom). Chiral amines are not optically active since the two enantiomers cannot be separated/isolated. (The enantiomers undergo rapid transversion through a trigonal planar transition state.)

The two enantiomers of chiral amines undergo rapid interconversion (through a trigonal planar intermediate state), so each individual enantiomer cannot be isolated.

pKa ≈ 35 Amines are weak acids and moderate bases.

pKa ≈ 10 Ammoniums are moderately acidic (i.e. more acidic than water/alcohol and less acidic than carboxylic acids).

Weakly Acidic The conjugate bases of amines (e.g. LDA, NaNH2) are strongly basic (due to the N—H bond being relatively strong/stable).

Moderately Basic The conjugate acids of amines (i.e. Ammoniums) are moderately acidic (due to the instability of a quadruple-substituted cationic Nitrogen compound).

• Conjugation • Hybridization • Aromaticity • The Nitrogen lone pair is less basic if it is in conjugation with a π system. • The Nitrogen lone pair is less basic if it is possesses a lower hybridization. • The Nitrogen lone pair is less basic if it is within an aromatic system.

• The Nitrogen lone pair is more basic if no conjugation is present (since the lone-pair electrons are more capable of attacking/reacting). • The Nitrogen lone pair is less basic if it is in conjugation with a π system (since the lone-pair electrons are less reactive/nucleophilic).