OChem topic 3 - configuration of molecules

configuration vs conformation

• the conformation of a molecule is the particular geometry that results from the spatial arrangement of its bonds - the same molecule can have different conformers - achieved through bond rotation

• the configuration of a molecule is the permanent geometry that results from the spatial arrangement of its bonds - to change the configuration of a molecule bonds must be broken - a different configuration is a different molecule

chirality

• molecules that cannot be superimposed on their mirror image are chiral - they are not the same molecule - they have different permanent geometries

• chiral molecules have no plane of symmetry

achiral molecule

• molecules with a plane of symmetry

isomers

• compounds with the same molecular formula

what are the two classification of isomers

• structural/constitutional isomers

• stereoisomers

constitutional isomers

• the same molecular formula but different connectivities of the atoms

stereoisomers

• same molecular formula and the same connectivity but different spatial arrangement of atoms

enantiomers

• stereoisomers that are non-superimposable mirror images

• chiral

• usually when all stereogenic centres have been inversed

racemic mixture

• a 50:50 mixture of a pair of enantiomers

enantiopure

• a sample containing only a single enantiomer

• enantiopurity refers to a measure of how enantiopure the compound is

stereogenic centre

• a carbon with 4 different groups

diastereoisomers

• molecules with the same molecular formula, same connectivity patterns but still different molecules who’s structures cannot be superimposed on each other (usually because one of the groups is on the opposite face than in the original molecule)

• not mirror images and cant interconvert through rotation about bonds

• have different spectral and physical properties to each other - can be either chiral or achiral

optical activity of enantiomers

• enantiomers have identical physical and spectral properties except that they rotate plane polarised light in different directions - referred to optical activity that can be measured using a polarimeter

• enantiomers will polarise light in the opposite sense (clockwise or anti) but to the same magnitude

• a racemic mixture will give a reading of zero in a polarimeter

specific rotation

= optical rotation / (concentration (g/dm3) x path length (dm))

racemised

• an enantioenriched mixture of the two enantiomers is undergoing a chemical bond-break and bond-forming process which is resulting in a racemic mixture of products

enantioenriched

• a mixture of two enantiomers where there is more of one of the enantiomers than the other

how is enantioenrichment/enantiopurity measured?

• enantiomeric excess (ee) or enantiomeric ratio (er)

enantiomeric excess

• ee = [(R-S)/(R+S)]x100

• r and s are the separate amounts or ratios of those enantiomers

• 0% ee = racemate

• 100% ee = enantiopure

enantiomeric ratio

• the ratio of the two enantiomers (called dr for diastereomeric mixtures)

• converting from ee = (100-%)/2 : 100-y

what are the labels used to differentiate between enantiomers?

• R and S - signify absolute stereochemistry

• assigned purely based on structure without any physical measurement being taken

how to assign R/S labels

1. identify stereogenic centre

2. assign priority number to each substituent (based on atomic number) - double and triple bonds are considered as bonding to two etc of the atoms in that multiple bond - referred to as ghost atoms

3. arrange molecule so the lowest priority substituent is pointing away

4. look at the direction of priority of the other three groups

5. clockwise = R

6. anticlockwise = S

how to determine how many stereoisomers there can be in a molecule with multiple stereogenic centres

• max of 2n

• but there are often fewer due to symmetry operation that result in certain stereoisomer being achiral ie. don’t have enantiomers - meso compounds - achiral members of a series of diastereoisomers

meso compounds

• 2 or more identical substituted stereocentres

• internal plane of symmetry so aren’t chiral

• can be superimposed on its mirror image

• stereocentres cancel out eg. one R and on S

separation of enantiomers

several ways to prepare enantiopure forms of chiral molecules

1. start from enantiopure material and do not racemise stereogenic centres during reaction - not always possible

2. asymmetric synthesis/catalysis where a chiral enantiopure reagent/catalyst is used in reaction step - a stereogenic centre forms to control which enantiomer forms

3. prepare a racemate of the compounds and then separate by resolution

how to separate enantiomer when they have the same physical and spectral properties

• take advantage of the facts diastereoisomers have different chemical and physical properties so can be separated

1. chemically transform mixture of enantiomers into new compounds which are diastereoisomers

2. separate diastereoisomers eg. by column chromatography

3. convert separated diastereoisomers back into the original enantiomers

1. A racemic (R/S) + B enantiopure (R)

2. AR-BR + AS-BR

3. bond breaking (AS+BR) or (AR+BR) pick which form of A you want