Optical Isomerism
LOs:
I can recall the meaning of structural and E-Z isomerism (geometric/cis-trans
isomerism) (4.8.1a)
I can demonstrate an understanding of the existence of optical isomerism
resulting from chiral centre(s) in a molecule with asymmetric carbon atom(s)
and understand optical isomers as object and non-superimposable mirror
images (4.8.1b)
I can recall optical activity as the ability of a single optical isomer to rotate the
plane of polarization of plane-polarized monochromatic light in molecules
containing a single chiral centre and understand the nature of a racemic
mixture (4.8.1c)
I can use data on optical activity of reactants and products as evidence for
proposed mechanisms, as in SN1 and SN2 and addition to carbonyl compounds
(4.8.1d)
Same molecular formula but different
arrangement of their atoms.
Atoms are
bonded in a
different order.
CHAIN
ISOMERISM
POSITIONAL
ISOMERISM
Atoms are bonded in the same
order but arranged differently in
space.
FUNCTIONAL
GROUP
ISOMERISM
GEOMETRIC
ISOMERISM
Rotation prevented
by double bond.
OPTICAL
ISOMERISM
Non- superimposable
mirror images.
E-Z vs cis-trans
- Draw cis and trans 1,2-dichloroethane
E-Z vs cis-trans
- Draw cis and trans 1,2-dichloroethane
E-Z vs cis-trans
• Now try and name these using the cis-trans
system
E-Z naming system
1. You look at what is attached to each end of
the double bond in turn, and give the two
groups a "priority" according to a set of rules.
The atoms with the higher atomic number take
priority.
E-Z naming system
If the two groups with the higher priorities are
on the same side of the double bond, that is
described as the (Z)- isomer. So you would write
it as (Z)-name of compound. The symbol Z
comes from a German word which means
together.
E-Z naming system
If the two groups with the higher priorities are
on opposite sides of the double bond, then this
is the (E)- isomer. E comes from the German
word which means opposite.
E-Z Isomers
Since Br has a higher atomic number than H, it
takes priority.
E-Z vs cis-trans
• Now try and name these using the E-Z system
E-Z vs cis-trans
• Now try and name these using the cis-trans
system
Z-1-bromo-2-chloro-1-fluoroethene
E-1-bromo-2-chloro-1-fluoroethene
Homework
E-pent-2-ene (trans)
Z-pent-2-ene (cis)
E-2-bromobut-2-ene (cis)
Z-2-bromobut-2-ene (trans)
E-1-chloro-2-methylbut-1-ene
Z-1-chloro-2-methylbut-1-ene
The cis–trans system breaks down for this pair of isomers.
Optical isomers:
• All molecules have a mirror image – but
for most molecules it is the same
molecule.
H
H
H
C
C
H
F
H
F
H
fluoromethane
20
• For some molecules the mirror image is a
different molecule (the mirror image is
non-superimposable).
H
OH
OH
C
C
COOH
CH3
(-) lactic acid
in sour milk
HOOC
H3C
H
(+) lactic acid
in muscles
21
• Left and right hands are an example
of non-superimposable mirror images.
22
• This usually happens when a molecule
contains a C atom with four different
groups attached (chiral / asymmetric C).
• Such molecules are said to be chiral or
optically active.
b
a
a
C
C
d
c
d
c
b
23
24
• The optical isomers are called enantiomers.
• These are distinguished by +/-, D/L or more
correctly R/S.
• A 50/50 mixture of the two enantiomers is
called a racemic mixture or a racemate.
25
TASK
Some of the following molecules
are optically active.
For each one, click its name below and
decide whether it is optically active or
not.
Click again to see if you are correct.
a) propan-2-ol
e) butanone
b) 2-chlorobutane
f) 2-methylbutanoic acid
c) 1-chlorobutane
g) butan-2-ol
d) 3-methylhexane
h) 1-chloro-3-methylpentane
26
propan-2-ol
CH3
CH
CH3
OH
NOT OPTICALLY ACTIVE
Click here to go back to the optical isomerism task
27
2-chlorobutane
CH3
CH
CH2
CH3
Cl
H
CH2CH3
CH2CH3
C
C
CH3
Cl
H3C
Cl
H
OPTICALLY ACTIVE
Click here to go back to the optical isomerism task
28
1-chlorobutane
CH2
CH2
CH2
CH3
Cl
NOT OPTICALLY ACTIVE
Click here to go back to the optical isomerism task
29
3-methylhexane
CH3 CH2 CH CH2 CH2 CH3
CH3
H
CH2CH2CH3
CH2CH2CH3
C
C
CH3
CH2CH3
CH3
CH3CH2
H
OPTICALLY ACTIVE
Click here to go back to the optical isomerism task
30
O
butanone
CH3
C
CH2
CH3
NOT OPTICALLY ACTIVE
Click here to go back to the optical isomerism task
31
propan-2-ol
CH3
CH
CH3
OH
NOT OPTICALLY ACTIVE
Click here to go back to the optical isomerism task
32
2-methylbutanoic acid
CH3
CH3
CH2
CH3
O
CH
C
CH2CH3
CH2CH3
C
C
H
COOH
H
HOOC
OH
CH3
OPTICALLY ACTIVE
Click here to go back to the optical isomerism task
33
OH
butan-2-ol
CH3
CH3
CH2
CH
CH3
CH2CH3
CH2CH3
C
C
H
OH
H
HO
CH3
OPTICALLY ACTIVE
Click here to go back to the optical isomerism task
34
CH3
1-chloro-3-methylpentane
CH3
CH3
CH2
CH
Cl
CH2
CH2
CH2CH3
CH2CH3
C
C
H
CH2CH2Cl
H
CH2ClCH2
CH3
OPTICALLY ACTIVE
Click here to go back to the optical isomerism task
35
• Molecules that are optical isomers are
called enantiomers.
• Enantiomers have identical chemical
and physical properties, except:
• Their effect on plane polarised light;
• Their reaction with other chiral molecules
36
Plane Polarised Light
ANALOGY:
Insert a vertical slit
plane polarised string
Add a second slit
The real thing - plane polarised light
• Light is also made up of vibrations - this time,
electromagnetic.
• Polaroid has the ability to screen out all the
vibrations apart from those in one plane and so
produce plane polarised light.
• If you wear one pair of Polaroid sunglasses and hold
another pair up in front of them so that the glasses
are held vertically rather than horizontally, you'll find
that no light gets through - you will just see darkness.
This is equivalent to the two slits at right angles in
the string analogy. The polaroids are described as
being "crossed".
Chiral Molecules
• Enantiomers:
– are optically active;
– have different effects on plane polarised light;
• A solution of one enantiomer rotates the plane of
polarisation in a clockwise direction named the (+)
form.
• The other enantiomer will rotate the plane of
polarisation in the other direction, named the (-)
form.
• A racemic mixture (racemate) has equal quantities
of both the enantiomers.
How can you tell that the plane of
polarisation has been rotated?
Optically active sample:
You can easily tell whether the plane of polarisation has been
rotated clockwise or anti-clockwise, and by how much.
• Chiral molecules often react differently
with other chiral molecules.
• This is like the idea that a right hand
does not fit a left handed glove – the
molecule must be the correct shape to
fit the molecule it is reacting with.
• Many natural molecules are chiral and
most natural reactions are affected by
optical isomerism.
44
• For example, most amino acids (and
so proteins) are chiral, along with
many other molecules.
• In nature, only one optical isomer
occurs (e.g. all natural amino acids are
rotate polarised light to the left).
45
• Many drugs are optically active, with one
enantiomer only having the beneficial
effect.
• In the case of some drugs, the other
enantiomer can even be harmful, e.g.
thalidomide.
46
• In the 1960’s thalidomide was given to
pregnant women to reduce the effects of
morning sickness.
• This led to many disabilities in babies and
early deaths in many cases.
The photographs are both from ‘Molecule of the Month’ at Bristol University:
http://www.chm.bris.ac.uk/motm/thalidomide/start.html
47
O
NH
O
O
O
H2C
NH
O
C
C
N
CH2
H
O
S thalidomide (effective drug)
O
N
H2C
CH2
H
O
R thalidomide (dangerous drug)
The body racemises each
enantiomer, so even pure S is
dangerous as it converts to R in
the body.
48
• Thalidomide was banned worldwide
when the effects were discovered.
• However, it is starting to be used again to
treat leprosy and HIV.
• Its use is restricted though and patients
have to have a pregnancy test first
(women!) and use two forms of
contraception (if sexually active).
49
CH3
CH3
O
O
H
C
CH2
H3C
S carvone (caraway seed)
Caraway Seed has a warm, pungent,
slightly bitter flavour with aniseed overtones.
H2C
C
H
CH3
R carvone (spearmint)
50
CH3
CH3
CH2
C
H
H
C
CH2
CH3
H3C
S limonene (lemons)
R limonene (oranges)
51
Stereochemistry and reaction
mechanisms
• What is the
difference between
Sn1 and Sn2?
52
Stereochemistry and reaction
mechanisms
• What is the
difference between
Sn1 and Sn2?
Sn1 involves one
species in the RDS and
produces a racemic
mixture
Sn2 involves two
species in the RDS and
produces an optically
active product
53
Sn2
Sn1
What would happen?
54
Stereochemistry and reaction
mechanisms
• SN1 reaction depends upon the degree of “shielding” of the
front side of the reacting carbon by the leaving group and its
associated solvent molecules.
•
If the leaving group does not get away from the carbocation
before the product-determining step takes place, there will
be some preference for nucleophilic attack at the back side
of the carbon, which results in a predominance of the
product of inverted configuration.
55
Optical Isomerism
LOs:
I can recall the meaning of structural and E-Z isomerism (geometric/cis-trans
isomerism) (4.8.1a)
I can demonstrate an understanding of the existence of optical isomerism
resulting from chiral centre(s) in a molecule with asymmetric carbon atom(s)
and understand optical isomers as object and non-superimposable mirror
images (4.8.1b)
I can recall optical activity as the ability of a single optical isomer to rotate the
plane of polarization of plane-polarized monochromatic light in molecules
containing a single chiral centre and understand the nature of a racemic
mixture (4.8.1c)
I can use data on optical activity of reactants and products as evidence for
proposed mechanisms, as in SN1 and SN2 and addition to carbonyl compounds
(4.8.1d)