Organic I - rotation values of mixtures and purifying isomers

What is an enantiomeric excess?

• When one enantiomer of the compound is in a higher proportion than the other

• Can calculate the effect on plane-polarised light using the proportion of each enantiomer and their optical rotation values

• Optical rotation values of a racemic mixture would be 0 - optical effects would cancel out

How can mixtures of enantiomers cause changes to properties?

• Pairs of enantiomers have identical physical properties

• A mixture of both can have different physical properties than either pure substance

• Intermolecular bonds between two enantiomers are weaker than bonds between identical molecules so less energy is needed to melt the mixture

What are the three methods that can be used to separate diastereoisomers?

• Fractional crystallisation

• Fractional distillation

• Chromatography

How can fractional crystallisation be used to separate diastereoisomers?

• Exploits the difference in melting points or solubility of diastereoisomers

• Change conditions so that one diastereoisomer ‘wants’ to crystallise but not the other

• Allows collection of the pure crystals

How can fractional distillation be used to separate diastereoisomers?

• Exploits differences in boiling points of diastereoisomers

• Heat a liquid mixture above the boiling point of one but not the other

• Collect the vapour that boils off

How can chromatography be used to separate diastereoisomers?

• Some methods may be able to separate diastereoisomers

• Different diastereoisomers may move through a column at different speeds or reach different distances

How can enantiomers be separated from a mixture?

• Pairs of enantiomers have identical physical properties so cannot use simple separation

• Need to resolve (form enantiomers) the mixture

What are the two methods to resolve a racemic mixture?

• Resolution through chromatography

• Resolution via diastereoisomers (chiral resolution)

How can chromatography help resolve a racemic mixture?

• Molecules of one enantiomer have a slightly greater affinity for each other than the other racemate

• When crystallised, pure crystals of the two enantiomers can grow - seed crystal that is optically pure is added to a supersaturated mix to encourage growth of separate crystals

• Rarely used as for most enantiomers the crystals will be racemate

How can chiral resolution help resolve a racemic mixture?

• Converts enantiomers to diastereoisomers in a reversible way, separates them and retrieves the original enantiomers

• Racemic mixture is reacted with an optically pure substance of a single isomer

• Ensures there are only two diastereoisomers to separate

How can kinetic resolution be used to resolve a racemic mixture?

• Natural enzymes will typically only catalyse reactants of a certain type present naturally - stereoselective

• Mixture is dissolved in organic solvents

• Enzyme will digest one form and not the other - forms a water-soluble salt

• Two substances can then be separated via solvent extraction

• Kinetic resolution exploits differences that a pair of enantiomers have in terms of reaction with a reactant/catalyst

• May need to modify reactants to fit the catalyst

How can chiral chromatography work to separate enantiomers?

• Enantiomers can have different levels of affinity for a stationary phase due to chirality - works if the molecules have different levels of affinity for the mobile phase and the stationary phase

• Enantiomers have the same chemistry with non-chiral reactants so most chromatography setups would not work

• Could work with a chiral stationary phase