Chem 336 - Spring 1999 - Organic Chemistry III
Portland State University - Dr. Carl C. Wamser

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Chapter 21 - Amines

Organic Compounds Containing Nitrogen

• a wide variety of functional groups, including combinations with oxygen

Classification of Amines

• primary (1°) - one C attached to N
• secondary (2°) - two C attached to N
• tertiary (3°) - three C attached to N
• quaternary (4°) - four C attached to N (and a positive charge)
  
• note the difference from other functional groups, which are classified according to the C to which the functional group is attached

Nomenclature of Amines

• IUPAC: amino- substituent
• common: alkyl amine
• Chemical Abstracts: alkanamine

Structure of Amines

• sp³ (tetrahedral) nitrogen including the lone pair
  
• tertiary amines usually cannot be isolated as separate enantiomers
  • amines undergo rapid pyramidal inversion
• quaternary amines could be chiral and isolable as separate enantiomers
• polar bonds make small amines water-soluble, good H-bonding
  

Spectroscopy of Amines

• IR: characteristic N-H stretch 3300 - 3500 cm-1
  • one N-H band for 2° amines, two bands for 1° amines
• NMR: chemical shift of N-H variable (like O-H), depends on H-bonding
  • rapid N-H exchange with solvent prevents splitting
• Mass Spec: Nitrogen Rule - odd parent peak implies odd number of nitrogen atoms

Basicity of Amines, Acidity of Ammonium Ions

• N lone pair relatively easily protonated

• note that K_b x K_a = [H⁺] [OH^-] = Kw = 10^-14
  or pK_a + pK_b = 14
• recall that when pH = pK_a , there are equal concentrations of the conjugate acid and conjugate base present (i.e., RNH₂ and RNH₃⁺ )
• for typical aliphatic amines, pK_b = 3 - 4
  so pK_a = 10 - 11 for their ammonium ions
  so at around pH 10 - 11 , RNH₂ and RNH₃⁺ are both present
• for typical aromatic amines, pK_b = 9 - 10
  so pK_a = 4 - 5 for their ammonium ions
  so at around pH 4 - 5 , ArNH₂ and ArNH₃⁺ are both present
• water solubility of amines can be easily changed with pH
  aromatic amines are water-soluble (protonated) below pH 4
  aliphatic amines are water-soluble (protonated) below pH 9
  

Basicity Trends

• aromatic amines are less basic due to resonance delocalization of the N lone pair

• amides are nonbasic due to strong delocalization of the N lone pair

• electron withdrawing effects decrease basicity
  because the N lone pair is less available for bonding to a proton
  

Optical Resolution

• a racemic mixture of a chiral amine can be separated into enantiomers if a sample of a chiral acid is available
  e.g., lactic acid or citric acid from natural sources are chiral
  
• the amine-acid salts (ammonium carboxylates) are diastereomers and may have distinctive properties that would allow them to be separated (e.g., solubility)
  

Preparations of Amines

• substitution reactions:
  S_N2 reaction of ammonia on alkyl halides
  but the amine product is still nucleophilic and further substitution often results
  primary amines can be made by using a great excess of NH₃ to avoid further substitution

• reduction reactions:

Reactions of Amines

• substitution reactions:
  S_N2 reactions on alkyl halides
  but oversubstitution is a problem, except for making quaternary ammonium ions

• acyl substitutions to make amides (usually from acid chlorides)
  

Diazonium Salts

• secondary amines react with HNO₂ (nitrous acid) to make N-nitrosoamines
• primary amines react with HNO₂ to form a diazonium ion (diazotization reaction)
  • aliphatic diazonium ions are unstable, give carbocations
  • possible products include rearrangements, eliminations, nucleophilic substitution
    
• aryl diazonium ions are relatively stable and can be replaced by many nucleophiles
• this method provides a good way to attach nucleophiles to aromatic rings
  
• Sandmeyer reactions : CuX as catalyst to convert diazonium ion to ArX

Elimination Reactions

• Hoffmann elimination - from a quaternary ammonium hydroxide
• Cope elimination - from a tertiary amine oxide

Pyrrole

• pyrrole is even more reactive than benzene in electrophilic aromatic substitution

• the porphine ring system is a tetrapyrrole - found in heme, chlorophyll, etc.

Pyridine

• pyridine is less reactive than benzene in electrophilic aromatic substitution

Imidazole

• a 5-membered heterocyclic ring with two N
• one N lone pair is availble for bonding (basic)
  pK_b for imidazole is close to 7
  it is a common acid (and base) catalyst in biological systems around pH 7

Alkaloids

• naturally occurring amines, such as morphine
  the alkaloid name comes from their basic (alkaline) properties