Chemistry Chapter 11: Amines

Chapter 11: Amines

• 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

Naming Amines

• 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⁻ )

Structure and Properties of Amines

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

Basicity of Amines

• 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

Synthesis of Amines

• 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

Hofmann and Curtius Rearrangements

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

Reactions of Amines

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

Hofmann Elimination

• 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

Orientation in Hofmann Elimination

• 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