Chemistry Chapter 11: Amines

Study Notes

Amines are organic derivatives of ammonia
Amines are stronger bases than alcohols, ethers, or water
Alkylamines are prepared via SN2 reaction of ammonia or an amine with an alkyl halide, or by Gabriel amine synthesis
Reductive amination is a reaction where a ketone or aldehyde is treated with an amine in the presence of a reducing agent such as NaBH₄
Amines can result from Hofmann and Curtius rearrangements of carboxylic acid derivatives
Hofmann elimination is a process where amines undergo E2 elimination to produce alkenes; the amines are quaternized first using iodomethane, then heated with silver oxide

Alkyl-substituted amines (alkylamines) are classified as primary (RNH₂), secondary (R₂NH), and tertiary (R₃N) based on the number of organic substituents attached to the nitrogen atom
Simple amines are named by adding the suffix "-amine" to the name of the alkyl substituent (e.g., tert-butylamine)
Symmetrical secondary and tertiary amines are named by adding the prefix "di-" or "tri-" to the alkyl group (e.g., diethylamine, triethylamine)
Unsymmetrical amines are named as N-substituted primary amines; the largest alkyl group is the parent name, and the other alkyl groups are considered N-substituents (e.g., N,N-dimethylpropylamine).
The suffix "-amine" can replace the final "-e" in the name of the parent compound (e.g., 4,4-dimethylcyclohexanamine)
Amines with more than one functional group are named by considering the -NH₂ as an amino substituent (e.g., 2-aminobutanoic acid)
Quaternary ammonium salts are compounds where a positively charged nitrogen atom has four attached groups (e.g., R₄N⁺X⁻ )

Amines with fewer than five carbon atoms are water-soluble
Primary and secondary amines form hydrogen bonds, which increases their boiling points

The lone pair of electrons on nitrogen makes amines basic and nucleophilic
Amines react with acids to form acid-base salts and react with electrophiles
The basicity of some common amines varies (pKa of ammonium ion) depending on the structure of the amine:
- Ammonia (NH₃): pKa ≈ 9.26
- Primary alkylamine (e.g., methylamine): pKa ≈ 10.64-10.75
- Secondary alkylamine (e.g., diethylamine, pyrrolidine): pKa ≈ 10.98-11.27
- Tertiary alkylamine (e.g., triethylamine): pKa ≈ 10.76

Amines can be prepared by the reduction of nitriles, amides, and nitro compounds using LiAlH₄
The simplest method of alkylamine synthesis is by SN2 alkylation of ammonia or an alkylamine with an alkyl halide.
Ammonia and other amines are good nucleophiles
Reductive amination of aldehydes and ketones. Ammonia, primary amines, and secondary amines yield primary, secondary, and tertiary amines, respectively via reductive amination

Carboxylic acid derivatives can be converted to primary amines by Hofmann or Curtius rearrangements with a loss of one carbon atom

Primary and secondary amines can be acylated by nucleophilic acyl substitution reactions using pyridine as a solvent.

Silver oxide is used in the elimination step to exchange hydroxide ion for iodide in the quaternary ammonium salt, providing a base for the elimination reaction
The major product in Hofmann elimination is the less highly substituted alkene, due to the steric hindrance caused by the large, substituted leaving group

The major product in Hofmann elimination is the less highly substituted alkene due to steric hindrance of the leaving group
The base must abstract a hydrogen from the least hindered position