chap 5

• Stereochemistry


  The study of the spatial arrangement of atoms in molecules and the effects of this arrangement on the chemical and physical properties of the molecules

  
• Isomers


  • Constitutional isomers - Same connectivity between atoms but different spatial arrangements

  Stereoisomers - Different spatial arrangements

  
• Chirality


  Handedness - The non-superimposability of an object and its mirror image
• Enantiomers


  The non-superimposable mirror images of chiral molecules

  
• Stereogenic carbon


  A tetrahedral carbon with 4 different attached groups that may render the molecule chiral

  
• Achiral compounds


  • Hexane

  1. methylpentane
• Plane of symmetry


  A molecule with an internal mirror plane cannot be chiral
• Cis and trans cyclic compounds


  • Cis-1,2-dichlorocyclohexane - Achiral

  Trans-1,2-dichlorocyclohexane - Chiral
• (R) and (S) stereochemical designations


  Gives the absolute stereochemistry at a given stereocenter
• Cahn-Ingold-Prelog rules


  Assign priority numbers to groups attached to chiral carbon

  Atom with highest atomic number gets highest priority #1

  In case of ties, look at next atom(s) along the chain

  Double and triple bonds treated like bonds to duplicate atoms
• Assigning (R) or (S)


  Lowest priority group (4) positioned away from you

  Determine direction of motion viewing remaining groups in ascending order

  Clockwise = (R), Counterclockwise = (S)
• Properties of enantiomers


  • Same boiling point, melting point, density, refractive index

  Different direction of rotation in polarimeter

  Different interaction with other chiral molecules like enzymes and receptor sites
• Optical activity


  Substances that cause rotation of plane polarized light
• Polarimetry


  Measurement of optical activity using a polarimeter

  Clockwise = dextrorotatory = d or (+)

  Counterclockwise = levorotatory = l or (-)

  Not related to (R) and (S)
• Specific rotation, [α]


  Observed rotation depends on length of cell, concentration, optical activity strength, temperature, and wavelength of light

  Standardized measurement conditions
• Calculating [α]D


  • Given: 1.00 g sample in 20.0 mL ethanol, 5.00 mL in 20.0 cm polarimeter tube at 25°C, observed rotation -1.25°

  Calculation: [α]D25 = (-1.25°)/(0.05)(2) = -12.5°
• If a compound has [α]D25 = -9.25°, it can be said with certainty that the compound is chiral
• Biological discrimination of enantiomers


  Enzymes are chiral and can distinguish between enantiomers, usually only one enantiomer fits properly into the active site
• The Thalidomides


  • (R)-enantiomer effective against morning sickness, (S)-enantiomer teratogenic and causes birth defects
• Racemic mixture


  A solution of equal amounts of two enantiomers, no optical activity
• Optical purity


  Also called enantiomeric excess, amount of pure enantiomer in excess of the racemic mixture
• Calculating optical purity


  • Given: Specific rotation of (S)-2-iodobutane is +15.90, specific rotation of mixture is -3.18

  Calculation: Optical purity = [-3.18/15.90] x 100% = 20%

  Composition: 60% (R), 40% (S)
• Chirality of conformers - If equilibrium exists between conformers, the conformers may or may not be chiral
• or () pair


  Also referred to as a Racemate
• No optical activity
• The mixture may have different b.p. and m.p. from the enantiomers
• Racemic Products


  If optically inactive reagents combine to form a chiral molecule, a racemic mixture of enantiomers is formed

  
• Optical Purity


  • Also called enantiomeric excess
  • Amount of pure enantiomer in excess of the racemic mixture
  • Calculated from the percent composition or from the observed and specific rotations
  • If o.p. = 50%, then the observed rotation will be only 50% of the rotation of the pure enantiomer
  • Mixture composition would be 75:25
• Chirality of Conformers


  • If equilibrium exists between two chiral conformers, molecule is not chiral
  • Judge chirality by looking at the most symmetrical conformer
  • Cyclohexane can be considered to be planar, on average

  
• Mobile Conformers


  • Nonsuperimposable mirror images, but equal energy and interconvertible
  • Use planar approximation
• Fischer Projections


  • Flat drawing that represents a 3D molecule
  • A chiral carbon is at the intersection of horizontal and vertical lines
  • Horizontal lines are forward, out-of-plane
  • Vertical lines are behind the plane
• Fischer Rules


  • Carbon chain is on the vertical line
  • Highest oxidized carbon at top
  • Rotation of 180 in plane doesn't change molecule
  • Do not rotate 90!
  • Do not turn over out of plane!
  • If a plane of symmetry is present, a given structure cannot be chiral!
• A rotation of 180° is allowed because it will not change the configuration
• A 90° rotation will change the orientation of the horizontal and vertical groups. Do not rotate a Fischer projection 90°!
• Fischer Mirror Images


  Easy to draw, easy to find enantiomers, easy to find internal mirror planes
• Fischer (R) and (S)


  • Lowest priority (usually H) comes forward, so assignment rules are backwards!
  • Clockwise 1-2-3 is (S) and counterclockwise 1-2-3 is (R)
• Diastereomers


  • Stereoisomers that are not mirror images
  • Can be Geometric isomers (cis-trans)
  • Alkenes
  • Cycloalkanes
  • Molecules with 2 or more stereocenters

  
• Alkenes


  • Cis-trans isomers are not mirror images, so these are diastereomers

  
• Ring Compounds

  • Cis-trans isomers possible
  • May also have enantiomers
  • Example: trans-1,3-dimethylcylohexane
• Two or More Stereocenters


  • May be Enantiomers, Diastereomers, or Meso compounds
  • Assign (R) or (S) to each chiral carbon
  • Enantiomers have opposite configurations at each corresponding chiral carbon
  • Diastereomers have some matching, some opposite configurations
  • Meso compounds have internal mirror plane
  • Maximum number of stereoisomers is 2n, where n = the number of stereocenters