Last units

• Heterocyclic compounds


  Ring compounds with elements other than C in the ring
• Most common elements in heterocyclic compounds

  • Oxygen (O)
  • Nitrogen (N)
  • Sulphur (S)
• Aliphatic heterocycles


  Similar to the open chain analogues (ethers, amines & sulphides)
• Unsaturated heterocycles


  Have unique & interesting properties
• Two thirds of all organic compounds are aromatic heterocycles
• Most pharmaceuticals are heterocycles
• Heterocycles used as pharmaceuticals


  • Quinine
  • Sildenafil
• Heterocycles used as pharmaceuticals


  • Topotecan
  • Irinotecan
  • Cimetidine
• Natural product


  Compound synthesized by a plant or an animal
• Alkaloids


  Natural products that contain one or more N heteroatoms
• Saturated cyclic amine


  Named as a cycloalkane, using the prefix "aza" to denote the N atom
• Heterocyclic rings


  Numbered so that the heteroatom has lowest possible #
• Precedence of heteroatoms


  O > S > N
• Heterocyclic names to know

  • Pyridine
  • Pyrrole
  • Furan
  • Thiophene
  • Imidazole
  • Pyrazole
  • Triazoles
  • Tetrazoles
  • Indole
  • Quinoline
  • Isoquinoline
• Basicity of heterocyclic amines

  Depends on the location of the electron pair of the nitrogen atom, its hybridization, and whether or not resonance stabilization is possible
• Pyridine


  • CH of benzene is replaced by a N atom (& a pair of electrons)
  • Hybridisation = sp2 with similar resonance stabilisation as benzene
  • Lone pair of electrons not involved in aromaticity
  • Pyridine is a weak base
  • Pyridine is electron deficient
  • Electrophilic aromatic substitution is difficult
  • Nucleophilic aromatic substitution is easy
• Pyridine vs alkylamines


  • Pyridine (pKa = 5.25) is a weaker base than alkylamines
  • Reason: Lone-pair e- on pyridine N are in an sp2 orbital, while those on alkylamine N are in an sp3 orbital
  • e- in an orbital with more s character are held more closely to the + charged nucleus & are less available for bonding (less basic)
  • sp2 hybridised N atom (33% s character) in pyridine is less basic than sp3 hybridised N in an alkylamine (25% s character)
• 1. character


  • The contribution of sigma type bonds in a hybridization
  • The more s-character a bond has, the shorter and stronger the bond is
• Pyrrole


  • Aromatic: 6 π electrons
  • Lone pair tied up in aromatic ring
  • Pyrrole is electron excessive
  • Electrophilic aromatic substitution is easy
  • Nucleophilic aromatic substitution is difficult
• Pyrrole vs aliphatic amines

  • N atom in pyrrole is less e- rich, less basic & less nucleophilic than N in an aliphatic amine
  • C atoms of pyrrole are more e- rich & more nucleophilic than typical = bond C's
  • Pyrrole ring – very reactive toward electrophiles
• Electrostatic potential maps


  • Pyrrole N is e- poor (less red) compared with N in its saturated counterpart pyrrolidine
  • Pyrrole C atoms are e- rich (more red) compared with C's in 1,3-cyclopentadiene
• 1. membered heterocycles with 2 or more Nitrogens

  • Diazoles
  • Imidazole
  • Pyrazole
  • Triazoles
  • 1,2,3-Triazole
  • 1,2,4-Triazole
  • Tetrazoles
• Imidazole


  More basic than pyridine, but more acidic than pyrrole
• Triazoles


  Weakly basic like pyridine, but more acidic than imidazole
• Tetrazoles


  pKa ~ 5 ~ RCOOH
• Indole is aromatic: 10 π electrons
• Indole


  • Has a non-basic, pyrrole-like N & undergoes electrophilic substitution more easily than benzene
  • Benzene part is non-reactive
  • Electrophilic aromatic substitution occurs at C3 of the e- rich pyrrole ring
• Quinoline & isoquinoline


  • Aromatic: 10 π electrons
  • Have basic, pyridine-like N atoms
  • Undergo electrophilic substitutions, although less easily than benzene
  • Reaction occurs on the benzene ring rather than on the pyridine ring
• Stereochemistry


  The field of chemistry that deals with the structures of molecules in three-dimensions
• Isomers


  Compounds that have the same molecular formula but which are not identical (have different structures)
• Chiral


  Object/molecule that has a nonsuperimposable mirror image
• Achiral


  Object/molecule that has a superimposable mirror image
• Stereoisomers


  Isomers that have their atoms connected in the same order but have different three-dimensional arrangements
• Asymmetric/Chiral centre


  An atom (usually C) that is bonded to four different groups & is therefore chiral
• Enantiomers/Optical isomers


  Stereoisomers of a chiral substance that have a mirror-image relationship
• Diastereomers


  Stereoisomers that are not mirror-images (not enantiomers)
• Optically active


  Compound that rotates the plane of polarised light. Chiral compounds are optically active
• Optically inactive


  Compound that does not rotate the plane of polarised light. Achiral compounds are optically inactive
• Classification of isomers


  • Structural isomers
  • Stereoisomers
• Structural isomers


  • Skeletal isomers: Structural isomers that differ in the branching of the aliphatic carbon chain
  • Positional isomers: Structural isomers that differ in the position of a FG or other substituent
  • Functional isomers: Structural isomers that have different FG's