Transcript optical isomerism

OPTICAL
ISOMERISM
A guide for A level students
KNOCKHARDY PUBLISHING
TYPES OF ISOMERISM
CHAIN ISOMERISM
STRUCTURAL ISOMERISM
Same molecular formula but
different structural formulae
POSITION ISOMERISM
FUNCTIONAL GROUP
ISOMERISM
E/Z ISOMERISM
STEREOISOMERISM
Same molecular
formula but atoms
occupy different
positions in space.
Occurs due to the restricted
rotation of C=C double bonds...
two forms - CIS and TRANS
OPTICAL ISOMERISM
Occurs when molecules have a
chiral centre. Get two nonsuperimposable mirror images.
OPTICAL ISOMERISM
Occurrence
another form of stereoisomerism
occurs when compounds have non-superimposable mirror images
Isomers
the two different forms are known as optical isomers or enantiomers
they occur when molecules have a chiral centre
a chiral centre contains an asymmetric carbon atom
an asymmetric carbon has four different atoms (or groups)
arranged tetrahedrally around it.
OPTICAL ISOMERISM
Occurrence
another form of stereoisomerism
occurs when compounds have non-superimposable mirror images
Isomers
the two different forms are known as optical isomers or enantiomers
they occur when molecules have a chiral centre
a chiral centre contains an asymmetric carbon atom
an asymmetric carbon has four different atoms (or groups)
arranged tetrahedrally around it.
CHIRAL CENTRES
There are four different colours
arranged tetrahedrally about
the carbon atom
2-chlorobutane exhibits optical isomerism
because the second carbon atom has four
different atoms/groups attached
OPTICAL ISOMERISM
SPOTTING CHIRAL CENTRES
Look at each carbon atom in the chain and see what is attached to it. For a chiral centre
you need an asymmetric carbon with four different atoms/groups) arranged tetrahedrally around it.
IF A CARBON HAS MORE THAN ONE OF ANY ATOM/GROUP ATTACHED, IT CAN’T BE CHIRAL
CH3CH2CH2CH2Cl
1-chlorobutane
C
C
C
C
3 H’s around it
2 H’s around it
2 H’s around it
2 H’s around it
NOT chiral
NOT chiral
NOT chiral
NOT chiral

OPTICAL ISOMERISM
SPOTTING CHIRAL CENTRES
Look at each carbon atom in the chain and see what is attached to it. For a chiral centre
you need an asymmetric carbon with four different atoms/groups) arranged tetrahedrally around it.
IF A CARBON HAS MORE THAN ONE OF ANY ATOM/GROUP ATTACHED, IT CAN’T BE CHIRAL
CH3CH2CH2CH2Cl
1-chlorobutane
CH3CH2CHClCH3
2-chlorobutane
C
C
C
C
3 H’s around it
2 H’s around it
2 H’s around it
2 H’s around it
NOT chiral
NOT chiral
NOT chiral
NOT chiral

C
C
C
C
3 H’s around it
2 H’s around it
H, CH3, Cl,C2H5 around it
3 H’s around it
NOT chiral
NOT chiral
CHIRAL
NOT chiral

OPTICAL ISOMERISM
SPOTTING CHIRAL CENTRES
Look at each carbon atom in the chain and see what is attached to it. For a chiral centre
you need an asymmetric carbon with four different atoms/groups) arranged tetrahedrally around it.
IF A CARBON HAS MORE THAN ONE OF ANY ATOM/GROUP ATTACHED, IT CAN’T BE CHIRAL
CH3CH2CH2CH2Cl
1-chlorobutane
CH3CH2CHClCH3
2-chlorobutane
(CH3)2CHCH2Cl
1-chloro-2-methylpropanane
(CH3)3CCl
2-chloro-2-methylpropanane
C
C
C
C
3 H’s around it
2 H’s around it
2 H’s around it
2 H’s around it
NOT chiral
NOT chiral
NOT chiral
NOT chiral

C
C
C
C
3 H’s around it
2 H’s around it
H, CH3, Cl,C2H5 around it
3 H’s around it
NOT chiral
NOT chiral
CHIRAL
NOT chiral

C 3 H’s around it
C 2 CH3’s around it
C 2 H’s around it
NOT chiral
NOT chiral
NOT chiral

C 3 H’s around it
C 3 CH3’s around it
NOT chiral
NOT chiral

OPTICAL ISOMERISM
Spatial differences between isomers
• two forms exist which are NON-SUPERIMPOSABLE MIRROR IMAGES of each other
• non-superimposable means you you can’t stack one form exactly on top of the other
OPTICAL ISOMERISM
Spatial differences between isomers
• two forms exist which are NON-SUPERIMPOSABLE MIRROR IMAGES of each other
• non-superimposable means you you can’t stack one form exactly on top of the other
Some common objects are mirror images and superimposable
superimposable but not mirror images
non-superimposable mirror images
spoons
books
hands
OPTICAL ISOMERISM
Spatial differences between isomers
• two forms exist which are NON-SUPERIMPOSABLE MIRROR IMAGES of each other
• non-superimposable means you you can’t stack one form exactly on top of the other
Some common objects are mirror images and superimposable
superimposable but not mirror images
non-superimposable mirror images
NB
For optical isomerism in molecules, both conditions must apply...
they must be mirror images AND be non-superimposable
spoons
books
hands
OPTICAL ISOMERISM
What is a non-superimposable mirror image?
Animation doesn’t
work in old
versions of
Powerpoint
OPTICAL ISOMERS - DIFFERENCE
•
•
•
•
•
isomers differ in their reaction to plane-polarised light
plane polarised light vibrates in one direction only
one isomer rotates light to the right, the other to the left
rotation of light is measured using a polarimeter
rotation is measured by observing the polarised light coming out towards the observer
OPTICAL ISOMERS - DIFFERENCE
•
•
•
•
•
isomers differ in their reaction to plane-polarised light
plane polarised light vibrates in one direction only
one isomer rotates light to the right, the other to the left
rotation of light is measured using a polarimeter
rotation is measured by observing the polarised light coming out towards the observer
• If the light appears to have
turned to the right
DEXTROROTATORY
d or + form
turned to the left
LAEVOROTATORY
l or - form
OPTICAL ISOMERS - DIFFERENCE
•
•
•
•
•
isomers differ in their reaction to plane-polarised light
plane polarised light vibrates in one direction only
one isomer rotates light to the right, the other to the left
rotation of light is measured using a polarimeter
rotation is measured by observing the polarised light coming out towards the observer
• If the light appears to have
turned to the right
DEXTROROTATORY
d or + form
turned to the left
LAEVOROTATORY
l or - form
Racemate
a 50-50 mixture of the two enantiomers (dl) or (±) is a racemic mixture.
The opposite optical effects of each isomer cancel each other out
Examples
Optical activity is common in biochemistry and pharmaceuticals
• Most amino acids exhibit optical activity
• many drugs must be made of one optical isomer to be effective
- need smaller doses (safer and cost effective)
- get reduced side effects
- improved pharmacological activity
OPTICAL ISOMERISM
The polarimeter
A
B
C
D
E
F
A
B
C
D
E
F
Light source produces light vibrating in all directions
Polarising filter only allows through light vibrating in one direction
Plane polarised light passes through sample
If substance is optically active it rotates the plane polarised light
Analysing filter is turned so that light reaches a maximum
Direction of rotation is measured coming towards the observer
If the light appears to have
turned to the right
DEXTROROTATORY
turned to the left
LAEVOROTATORY
OPTICAL ISOMERISM
How optical isomers can be formed
Carbonyl compounds undergo nucleophilic addition. If there are two different
groups attached to the C=O bond, the possibility of forming optical isomers arises.
THE NUCLEOPHILIC ADDITION OF HCN TO ETHANAL
If the nucleophilic cyanide ion
attacks from above one
optical isomer is formed
OPTICAL ISOMERISM
How optical isomers can be formed
Carbonyl compounds undergo nucleophilic addition. If there are two different
groups attached to the C=O bond, the possibility of forming optical isomers arises.
THE NUCLEOPHILIC ADDITION OF HCN TO ETHANAL
If the nucleophilic cyanide ion
attacks from above one
optical isomer is formed
However, attack from below,
gives the non-superimposable
mirror image of the first
OPTICAL ISOMERISM
How optical isomers can be formed
Carbonyl compounds undergo nucleophilic addition. If there are two different
groups attached to the C=O bond, the possibility of forming optical isomers arises.
THE NUCLEOPHILIC ADDITION OF HCN TO ETHANAL
If the nucleophilic cyanide ion
attacks from above one
optical isomer is formed
However, attack from below,
gives the non-superimposable
mirror image of the first
The reaction produces a mixture of the two optical
isomers because both modes of attack are possible
OPTICAL ISOMERISM
Synthesis of 2-hydroxypropanoic acid (lactic acid)
LACTIC ACID can be formed from ethanal in a two stage process.
1. Nucleophilic addition of hydrogen cyanide to ethanal
2 Hydrolysis of the nitrile group
HCN
H+ / H2O
OPTICAL ISOMERISM
Synthesis of 2-hydroxypropanoic acid (lactic acid)
LACTIC ACID can be formed from ethanal in a two stage process.
1. Nucleophilic addition of hydrogen cyanide to ethanal
2 Hydrolysis of the nitrile group
HCN
During the first stage, the nucleophilic CN- ion
can attack from below, or above, the aldehyde.
A mixture of the two enantiomers is formed.
H+ / H2O
OPTICAL ISOMERISM
Synthesis of 2-hydroxypropanoic acid (lactic acid)
LACTIC ACID can be formed from ethanal in a two stage process.
1. Nucleophilic addition of hydrogen cyanide to ethanal
2 Hydrolysis of the nitrile group
HCN
During the first stage, the nucleophilic CN- ion
can attack from below, or above, the aldehyde.
A mixture of the two enantiomers is formed.
Acid hydrolysis of the mixture provides a
mixture of the two lactic acid forms.
H+ / H2O
OPTICAL ISOMERISM - THALIDOMIDE
The one obvious difference between optical isomers is their response to plane
polarised light. However, some naturally occurring molecules or specifically
synthesised pharmaceuticals show different chemical reactivity.
The drug, THALIDOMIDE is a chiral molecule and can exist as two enantiomers. In the
1960’s it was used to treat anxiety and morning sickness in pregnant women.
Tragically, many gave birth to children with deformities and missing limbs.
It turned out that only one of the enantiomers (the structure on the right) was effective
and safe; its optically active counterpart was not. The major problem was that during
manufacture a mixture of the isomers was produced. The drug was banned worldwide, but not after tens of thousands of babies had been affected.
OPTICAL ISOMERISM – Other points
The following points are useful when discussing reactions producing optical isomers.
The formation of racemic mixtures is more likely in a laboratory reaction
than in a chemical process occurring naturally in the body.
If a compound can exist in more than one form, only one of the optical
isomers is usually effective.
The separation of isomers will make manufacture more expensive.
A drug made up of both isomers will require a larger dose and may cause
problems if the other isomer is ‘poisonous’ like thalidomide.