Lecture 5

• Amines


  A class of organic compound of general formula: RNH2, where R is an alkyl or aryl group
• Amine structure


  • Similar to ammonia (NH3), with nitrogen sp3 hybridised
  • Bond angle larger than ammonia due to greater Van der Waals repulsion
• Ammonia and trimethylamine structures

  • Ammonia: trigonal bipyramidal, nitrogen sp3 hybridised
  • Trimethylamine: nitrogen sp3 hybridised
• IUPAC nomenclature for amines

  • Select longest continuous carbon chain as root name
  • Change alkane ending to 'amine'
  • Number position of amino group
  • Name substituents in alphabetical order
• Amine nomenclature examples


  • 2-butanamine
  • 3-methyl-1-butanamine
  • Aniline and derivatives
• Amine classification


  Primary, secondary, tertiary, quaternary
• Primary amine


  • NH2 group bonded to carbon with two hydrogens
• Secondary amine


  • One hydrogen in NH2 replaced by R group
• Tertiary amine


  • Both hydrogens in NH2 replaced by two R groups
• Quaternary amine


  • Nitrogen bonded to four R groups, positively charged
• Polarity of amines


  Polar molecules due to charge separation and dipole moment
• Hydrogen bonding of amines

  • Primary amines are hydrogen bond donors and acceptors
  • Secondary amines are hydrogen bond donors and acceptors
  • Tertiary amines are only hydrogen bond acceptors
• Boiling points of amines

  Tertiary amines have lower boiling points than primary and secondary amines of similar molecular weight
• Solubility of amines


  • Soluble in polar organic solvents
  • Lower molecular weight amines up to 6 carbons are relatively soluble in water
• Amine odour


  Characteristic odour of rotten fish (putresine)
• Amine basicity


  Amines can act as nucleophiles and bases due to lone pair of electrons on nitrogen
• Amine nucleophilicity


  Amine donates lone pair to electrophilic carbon, forming new N-C bond
• Amine basicity constant (Kb)

  Measure of amine basicity, pKb = -log10[Kb]
• Amine preparation from alkyl halides


  Alkyl halide reacts with NH3 to form quaternary ammonium salt, then deprotonated to amine
• Disadvantage of direct alkylation is mixture of products, which are difficult to purify.
• Amine preparation from nitriles

  Nitrile reduced with LiAlH4 to form amine
• Amine preparation from Schiff bases and oximes

  Schiff base and oximes reduced with LiAlH4 to form amine
• Reaction of aliphatic amines with acid chlorides


  Forms amide (primary amide)
• Amide linkages


  Component of proteins
• Reaction of primary amines with nitrous acid


  Forms diazonium salt
• Reactions of diazonium salts

  1. Hydrolysis to hydroxyl compound

  2. Sandmeyer reaction with cuprous halides

  3. Reaction with cyanide to form nitrile

  4. Reduction with hypophosphorous acid to form alkane
• Amines as leaving groups


  NH2 group not usually a good leaving group, but can be made one by reaction with methyl iodide
• Hoffmann elimination


  Quaternary ammonium hydroxide formed, then decomposes to alkene and trimethylamine
• Reaction of amines with aldehydes and ketones

  1. Forms condensation product called carbinolamine

  2. Carbinolamine dehydrates to form Schiff base
• Amines


  Have many uses in Biology such as bioregulation, neurotransmission and defense against predators
• Because of their high degree of biological activity, many amines are used as drugs and medicines
• Alkaloids


  An important group of biologically active amines, synthesized mostly by plants as protection from being eaten by insects and other animals
• Acetylcholine


  A neurotransmitter that carries impulses to receptor cells, contains a quaternary ammonium group, is highly soluble in water and highly diffusible, released by the presynaptic membrane in the neuron in packets of about 104 molecules
• 1. Nitrosoamines are very powerful carcinogens which scientists fear may be present in many foods, especially in cooked meats that have been cured with sodium nitrite
• Biologically active amines:

  • Dopamine: a neurotransmitter
  • Epinephrine: An adrenal hormone
  • Amphetamine: an addictive stimulant
  • Pyridoxine, a component of Vitamin B6
  • Estradiol, a Female sex hormone or drug.
  • Mescaline: Psychedelic protoalkoloid
  • Serotonin: a neurotransmitter (regulates mood etc.)
  • Piperazine: antihelminth)
  • Nicotinic acid: niacin, a vitamin
  • Histamine: dilates blood vessels