Chirality (Edexcel A Level Chemistry): Revision Note

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

  • Chiral comes from the Greek word cheir, 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

The Nature of a Racemic Mixture

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 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 & Mechanisms

• 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 product will be formed