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 or alkanamine
- common: alkyl amine
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 Kb x Ka = [H+] [OH-]
= Kw = 10-14
or pKa + pKb = 14
- recall that when pH = pKa , there are equal concentrations
of the conjugate acid and conjugate base present (i.e., RNH2 and
RNH3+ )
- for typical aliphatic amines, pKb = 3 - 4
so pKa = 10 - 11 for their ammonium ions
so at around pH 10 - 11 , RNH2 and RNH3+ are
both present
- for typical aromatic amines, pKb = 9 - 10
so pKa = 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
Preparations of Amines
- substitution reactions:
SN2 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
Reactions of Amines
- substitution reactions:
SN2 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)
pKb 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
