7.1.1 Chirality

Optical isomers

• A carbon atom that has four different atoms or groups of atoms attached to it is called a chiral carbon or chiral centre
  • Chira comes from a Greek word meaning hand, so we talk about these molecules having a handedness

• The carbon atom is described as being asymmetric, i.e. there is no plane of symmetry in the molecule
• Compounds with one chiral centre (chiral molecules) exist as two optical isomers, also known as enantiomers
• Just like the left hand cannot be superimposed on the right hand, enantiomers are non-superimposable
  • Enantiomers are mirror images of each other

A molecule has a chiral centre when the carbon atom is bonded to four different atoms or group of atoms; this gives rises to enantiomers

Properties of optical isomers

• The chemical properties of optical isomers are generally identical, with one exception
  • Optical isomers interact with biological sensors in different ways
    • For example, one enantiomer of carvone smells of spearmint, while the other smells of caraway
      
      

                         Carvone optical isomers have distinctive smells

• Optical isomers have identical physical properties, with one exception
  • Isomers differ in their ability to rotate the plane of polarised light

When unpolarised light is passed through a polariser, the light becomes polarised as the waves will vibrate in one plane only

• The major difference between the two enantiomers is:
  • One enantiomer rotates plane polarised light in a clockwise manner and the other in an anticlockwise fashion
  • A common way to differentiate the isomers is to use (+) and (-), but there are other systems using d and l, D and L, or R and S

• The rotation of plane polarised light can be used to determine the identity of an optical isomer of a single substance
  • For example, pass plane polarised light through a sample containing one of the two optical isomers of a single substance
  • Depending on which isomer the sample contains, the plane of polarised light will be rotated either clockwise or anti-clockwise by a fixed number of degrees

Each enantiomer rotates the plane of polarised light in a different direction

• A racemic mixture (or racemate) is a mixture containing equal amounts of each enantiomer
  • One enantiomer rotates light clockwise, the other rotates light anticlockwise

• A racemic mixture is optically inactive as the enantiomers will cancel out each others effect
  • This means that the plane of polarised light will not change
    
    

           Racemic mixtures are optically inactive

Racemic mixtures and drugs

• In the pharmaceutical industry, it is much easier to produce synthetic drugs that are racemic mixtures than producing one enantiomer of the drug
• Around 56% of all drugs in use are chiral and of those 88% are sold as racemic mixtures
• Separating the enantiomers gives a compound that is described as enantiopure, it contains only one enantiomer
• This separation process is very expensive and time consuming, so for many drugs it is not worthwhile, even though only half the of the drug is pharmacologically active
• For example, the pain reliever ibuprofen is sold as a racemic mixture

The structure of ibuprofen showing the chiral carbon that is responsible for the racemic mixture produced in the synthesis of the drug

• Optical activity can be used to suggest the mechanism of a chemical reaction
• This is particularly the case for nucleophilic substitution
  • Nucleophilic substitution can occur via an S_N1 or S_N2 mechanism

S_N1 mechanism

• The S_N1 mechanism is a two-step reaction
  • In the first step, the C-X bond breaks heterolytically and the halogen leaves the halogenoalkane as an X^- ion
  • This leaves a trigonal planar, tertiary carbocation 
  • In the second step, the planar, tertiary carbocation is attacked by the nucleophile
  • The nucleophile is able to attack from either side of the planar carbocation, which results in the formation of a racemic mixture
• Therefore, a reaction with an S_N1 mechanism will produce a racemic mixture
                                                               S_N1 Optical Isomers Mechanism

S_N2 mechanism

• The S_N2 mechanism is a one-step reaction
  • The nucleophile donates a pair of electrons to the δ+ carbon atom of the halogenoalkane to form a new bond
  • At the same time, the C-X bond is breaking and the halogen (X) takes both electrons in the bond 
  • The halogen leaves the halogenoalkane as an X^- ion

• For example, the nucleophilic substitution of bromoethane by hydroxide ions to form ethanol

The S_N2 mechanism of bromoethane with hydroxide causing an inversion of configuration

• The bromine atom of the bromoethane molecule causes steric hindrance
• This means that the hydroxide ion nucleophile can only attack from the opposite side of the C-Br bond
  • Attack from the same side as the bromine atom is sometimes called frontal attack
  • While attack from the opposite side is sometimes called backside or rear-side attack

• As the C-OH bond forms, the C-Br bond breaks causing the bromine atom to leave as a bromide ion
  • As a result of this, the molecule has undergone an inversion of configuration
  • The common comparison for this is an umbrella turning inside out in the wind

Inversion of configuration - umbrella analogy

• Therefore, if a reaction with an S_N2 mechanism starts with an enantiopure reactant then an enantiopure products will be formed