Isomerism

Chain isomers are a type of structural isomer that have the same molecular formula but different arrangement of the carbon skeleton, hence a different structural formula. They are often described according the the amount of branching present and generally only differ in physical properties.

Methylpropane and butane are examples of chain structural isomers.

Functional group isomers have the same molecular formula but different functional groups, hence a different structural formula.

In this type of structural isomerism the reactivity differs greatly between isomers.

Positional isomers have the same molecular formula but different positions of functional groups on the carbon chain, hence a different structural formula.

This is a type of structural isomerism.

Propan-1-ol and propan-2-ol are structural isomers which exhibit differences in physical properties and reactivity.

In an alkene, restricted rotation around the carbon-carbon double bond gives two discrete sides to the bond. Where the bond is drawn horizontally, the sides are above and below the double bond.

When both carbons involved in the double bond are bonded to two different groups then E/Z stereoisomers are possible.

This alkene will have E/Z isomers since both the left and the right carbon are bonded to two different groups.

cis/trans isomerism is special case of E/Z isomerism. This is only used when at least one group on carbon 1 matches a group on carbon 2.

Where the matching groups are on opposite sides then ‘trans’ is used in the naming of the compound.

Similarly ‘cis’ is used where the matching groups are on the same side.

In pent-2-ene, each carbon in the is bonded to a single hydrogen.

The hydrogen groups can both sit on the same side of the double bond or on opposite sides; cis/trans isomerism exists in pent-2-ene.

E and Z descriptors are used to differentiate between stereoisomers and are based on the position of the two highest priority groups.

Group priority is assigned using the Cahn–Ingold–Prelog (CIP) rules:

• Groups are assessed based on the first point of difference, starting with the atom directly bonded to the carbon.
• The atom with the highest atomic number is given the highest priority.
• For isotopes, the atom with the highest atomic mass is given the highest priority.
• Where no difference is present in the atoms directly bonded to the carbons, consider the next connected atoms using the same rules.

If the highest priority groups are on opposite sides of the double bond, it is the E stereoisomer, from the German for opposite ‘entgegen’.

If the highest priority groups are on the same side of the double bond, it is the Z stereoisomer, from the German for together ‘zusammen’.

The configuration of E and Z stereoisomers is the opposite to the visual shape of the letter.

To recall which configuration is linked to which descriptor, remember ‘ it’s not what it looks like! ’.

The presence of a within the structural formula is often but not always indicated by the connecter.

To draw E/Z isomers:

• Identify the groups bound to each carbon in .
• Redraw the structure with the adjoining groups in the A, B, C, and D positions.

• Study the relative position of matching groups to assign cis and trans and/or use Cahn–Ingold–Prelog rules to assign E and Z to the stereoisomers drawn.

If there are two matching groups on the same carbon then symmetry means there will be no stereoisomers.

To check for unidentified alkene groups, count the number of bonds formed by each carbon in the formula, assuming all bonds to other carbons are single.

Assigning E and Z to a structure

The two bonded atoms on the left hand carbon are and . By the CIP priority rules, has a higher atomic number and is higher priority than .

The two bonded atoms on the right hand carbon are and , with having the higher atomic number and therefore higher priority.

Since the two higher priority groups are both on the same side of the double bond, they are zusammen (together). This is the Z isomer.

A chiral carbon atom that bonds to four different atoms or groups has no plane of symmetry. This is known as a chiral centre.

A chiral carbon atom can exist as optical isomers.

Enantiomers, otherwise known as optical isomers, are non-superimposable mirror images of each other.

Optical isomers have similar chemical and physical properties, but they rotate plane polarised light in different directions.

One enantiomer will rotate the plane of plane-polarised light clockwise and the other enantiomer rotates it by the same amount but anticlockwise.

Optical isomers are based on the tetrahedral geometry.

In most cases, they are drawn with two bonds on the plane of the paper (lines), one bond emerging (bold wedge) and one bond receding (dashed wedge).

A racemic mixture contains equal amounts of two optical isomers (enantiomers). These will both rotate the plane of plane-polarised light by the same amount, but in opposite directions.

This means that overall, there will be no optical rotation as the effects of both enantiomers effectively cancel each other out.

A racemic mixture may form when a reactant, or intermediate in a reaction mechanism, has a trigonal planar group.

Planar groups can be approached from both sides by an attacking species.

During the nucleophilic addition of HCN to aldehydes or ketones, when the planar carbonyl group is approached by the nucleophile, there is an equal probability that the cyanide attacks from the front or back face of the carbonyl.

This results in the formation of a racemate.

In an SN2 reaction, inversion of stereochemistry occurs because the nucleophile attacks the electrophilic carbon from the opposite side of the leaving group.

This ‘ backside attack ’ pushes the groups around the carbon into the opposite configuration, flipping the stereochemistry like an umbrella turning inside out.

This means that the product will have opposite optical activity compared to the reactants.

In SN1, any optical activity will be lost completely as the reaction proceeds via a planar intermediate. The product will be a racemic mixture of two stereoisomers.

Octahedral and square planar complexes can exhibit cis–trans isomerism.

As long as the complex ion has exactly two matching ligands that are different to the rest, they can exhibit cis–trans isomerism.

Optical isomers are stereoisomers that are a pair of non-superimposable mirror images of each other.

Optical isomers most commonly occur in octahedral or tetrahedral shaped complexes and must have bidentate or multidentate ligands.

Below is an example of optical isomerism shown by the complex ion.

Cis-platin is an effective anticancer drug.

It is only the cis isomer of the platinum complex that is effective.

Trans-platin is not a suitable alternative or accompaniment for cis-platin; it is clinically ineffective but still produces toxic side effects.

Cis-platin mechanism of action:

This complex binds to the DNA of rapidly replicating cancer cells.

Binding can only occur when the chloride ligands are in the cis arrangement.

This interaction results in the DNA structure of the cancer cells being altered, preventing further cell division.

The activation of the cell’s own repair mechanism eventually results in cell death.