Chemistry 332 - Spring 1996
Elements of Organic Chemistry II

Professor Carl C. Wamser

Chapter 12 - Amines

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

• 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
  

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

• sp³ (tetrahedral) nitrogen including the lone pair
  
• polar bonds make small amines water-soluble, good H-bonding

• 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

• 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

• 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)

• 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:

• 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)

• primary amines react with HNO₂ (nitrous acid) in a diazotization reaction
  
  
• aryl diazonium ions are relatively stable but can be replaced by many nucleophiles
  this method provides a way to attach nucleophiles to aromatic rings
  recall that most aromatic substitutions were electrophilic substitutions
• Sandmeyer reactions - CuX as catalyst to convert diazonium ion to ArX

• a 5-membered heterocyclic ring
• aromatic, because there are six pi electrons (including the N lone pair)
  pyrrole is not basic because the N lone pair is used in the aromaticity
• pyrrole is even more reactive than benzene in electrophilic aromatic substitution

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

• a 6-membered heterocyclic ring
• aromatic, because there are six pi electrons (3 double bonds)
  pyridine is basic because the N lone pair is available for bonding
• pyridine is less reactive than benzene in electrophilic aromatic substitution

• 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

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

• assign correct names to amine structures or assign structures to names
• characterize amines as primary, secondary, or tertiary
• use pK_a and/or pK_b values to predict the state of ionization of amines under various conditions
• illustrate the use of acid-base reactions in optical resolution of racemic mixtures
• prepare amines by substitution or reduction reactions
• prepare and use diazonium ions for aromatic syntheses
• differentiate between pyrrole, pyridine, and imidazole with respect to their bonding and acid-base chemistry