Chemistry 1102

Charlie Bond
MCS Rm 4.16/4.27
Charles.Bond@uwa.edu.au
What is Organic Chemistry?
Organic Reactions I II
Alkanes (Ch 21)
Conformational Analysis (Ch 21)
Stereochemistry I II III (Ch 22)
Alkyl Halides I II (Ch 24)
Alcohols and Ether I II (Ch 24)

Problems from Brown & LeMay

Ch 22
22.1 - 22.33 except 22.4-6, 22.17, 22.24,
22.25

What is stereochemistry?
Chemistry is not flat. It occurs in 3 dimensions.
There are limitations in how we present chemical
compounds and reactions on paper.

Need to learn to think in 3D. This is easier for some

people than others.

What is stereochemistry?
Stereochemistry: The branch of chemistry
that deals with spatial arrangements of
atoms in molecules and the effects of
these arrangements on the chemical and
physical properties of substances.
You will cover E and Z isomers of alkenes
later this is a kind of stereochemistry
OH

powerful, intensely green, grassy odor

OH

has a more fruity odor

Chirality

A different kind of stereoisomerism which

is more 3-dimensional is chirality.
Lord Kelvin 1884 I call any geometrical
figure chiral, and say it has chirality, if its
image in a plane mirror cannot be brought
to coincide with itself (from the Greek for
hand)
1975 Nobel prize for Chemistry:
Vladimir Prelog
(http://hrcak.srce.hr/file/8822)

Chiral

The two partner objects which are chiral

are called enantiomorphs or
enantiomers.
Hands are the simplest examples

Objects which are not chiral are achiral.

Chirality in 2 Dimensions
Tetris pieces:
Object

Mirror Reflection

Original

Identical? Chiral/achiral

achiral

Y
Y
N

achiral

N
N
N

chiral

achiral
chiral

chiral
chiral

Mirror symmetry

Chirality in practise: Tetris

Compare two scenarios in tetris:

No matter how many times you rotate the blue piece, it will not fit.
It's enantiomorph, the purple piece will fit nicely in a couple of places.
In a 3D world you could just flip the blue piece over and it would look like the purple
piece, but in Tetris (2D) world you can only rotate it.
In 2D, the blue and purple pieces are enantiomorphs.

Chirality in Practise: Letters

Achiral:

Chiral:

ABBA

ACDEHIMOTUVWXY
MOUTHY | YHTUOM
BFGJKLNPQRSZ
GNP | PNG

AOXOMOXOA

TOYS R US

Chirality in 3 Dimensions

Are all of these items chiral?

Clayden et al Organic Chemistry Ch 16 on Stereochemistry: PDF currently

available on www.oup.co.uk website.

Back to Chemistry:
Isomers

Enantiomers
Enantiomers: nonsuperposable mirror
images
as an example of a molecule that exists as a
pair of enantiomers, consider 2bromopentane

Enantiomers
one way to see that the mirror image of 2butanol is not superposable on the original is
to rotate the mirror image
180 OH

OH
H3 C

C H
CH2 CH3

Originalmolecule

H C CH
3
CH3 CH2
Mirrorimage

Themirrorimage
turnedby180

rotatethe
mirrorimage
by180about
theCOHbond

OH
H3 C

C CH CH
2
3
H
OH

Theoriginalmolecule

C H
H3 C
CH2 CH3

OH
C CH CH
2
3
H
Themirrorimage
rotatedby180
H3 C

Different molecules:
non-superimposable
mirror images
Enantiomers.

Enantiomers

Molecules with superposable mirror images are said to be achiral. Achiral

molecules possess a plane of symmetry

As an example of an achiral molecule, consider 2-propanol

notice that this molecule has no stereocentre

OH
C H
H3 C
CH3
Originalmolecule

OH
H C CH
3
H3 C
Mirrorimage

Enantiomers

The most common cause of enantiomerism in organic

molecules is the presence of a carbon with four different
groups bonded to it
a carbon with four different groups bonded to it is called a
stereocentre, a stereogenic centre or a chiral centre.
Chiral

Achiral

Enantiomers

To summarize

an object that is nonsuperposable on its mirror

image is chiral (it shows handedness)
the most common cause of chirality among
organic molecules is the presence of a carbon
with four different groups bonded to it
we call a carbon with four different groups bonded
to it a stereocentre
an object that is superposable on its mirror image
is achiral (without chirality)
nonsuperposable mirror images are called
enantiomers
enantiomers, like gloves, always come in pairs

Drawing Enantiomers
Following are four different representations for one of the
enantiomers of 2-butanol
OH
C H
H3 C
CH2 CH3
(1)

H OH
H3 C

C
CH2 CH3
(2)

H OH

OH

(3)

(4)

both (1) and (2) show all four groups bonded to the
stereocenter and show the tetrahedral geometry
(3) is a more abbreviated line-angle formula; although
we show the H here, we do not normally show them
in line-angle formulas
(4) is the most abbreviated representation; you must
remember that there is an H present on the
stereocentre

Drawing Mirror Images

on the left is one enantiomer of 2-butanol
on the right are two representations for its
mirror image (in this case, its enantiomer)
OH
Oneenantiomer
of2butanol

OH

OH

Alternativerepresentations
foritsmirrorimage

Often, an asterisk (*) is used to indicate a

stereocentre
OH
*

Indeterminate Chirality
If we dont know the stereochemistry of a
compound,
or we are talking about both enantiomers,
We can use wiggly lines to represent the
ambiguity:

Identifying Chirality
Q. Which of the following molecules are chiral? Identify the
stereogenic centre(s).

Cl
H
I

Br
H
H

NH2

H
HO2C

CO2H

CH2CH3

CH3
F

H2 N

H3C

CH3
OH

Which is the odd one out?

Which is the odd one out?

Which is the odd one out?

Assigning Chirality
Enantiomers are different compounds.
So it is necessary to be able to describe the handedness
(configuration) of stereogenic centres.
Vladimir Prelog, along with Cahn and Ingold, developed a
convention for assigning chiral centres as R or S. (They also
invented the E,Z notation used for alkenes)
Consider the amino acid alanine:
1. Identify the stereogenic centre

H3N

CO2
CH3

2. Draw the molecule to illustrate its tetrahedral nature.

H3N

CO2

H CH3

Assigning Chirality
3. Assign priority to the 4 substituents.
3a. Priority increases with atomic number (1 is highest).
H3N
CO2
1
2/3
H CH3
4

3b. If two (or more) of the atoms attached to the stereogenic

carbon are the same, consider the next atoms in the chain.
2
CO2

H3N
1
H CH3
4 3

Panic what is Priority?

Priority rules
1. Priority is based on atomic number; the higher the atomic
number, the higher the priority
(1)

(6)

(7)

(8)

(16)

(17)

(35)

(53)

-H

-CH3

-NH2

-OH

-SH

-Cl

-Br

-I

Increasingpriority
2. If priority cannot be assigned on the basis of the atoms
bonded directly to the double bond, look to the next set of atoms;
priority is assigned at the first point of difference
(1)

-CH2 -H

(6)

-CH2 -CH3

(7)

-CH2 -NH2

(8)

-CH2 -OH

Increasingpriority

- 3. Atoms participating in a double or triple bond are considered to

be bonded to an equivalent number of similar atoms by single
C C
bonds
istreatedas
-CH=CH2
-CH-CH2

Assigning Chirality

4. Arrange the molecule so that the lowest priority substituent is

pointing away from you (into page).
2
H3N
CO2
1
H CH3
4 3

NH3
1
H CH3
4 3

flip horizontal

2
O2C

5. Mentally, move from 1-2-3.

If rotation is clockwise

2
O2C

NH3
1
H CH3
4 3

If rotation is anticlockwise

anticlockwise
S-alanine

Remember: R is for Right

From the latin: Sinister, Rectus

Assigning R/S

Cl
H
I

Br
H
H

NH2

H
HO2C

CO2H

CH2CH3

CH3
F

H2 N

H3C

CH3
OH

Brainbuster
NOTE: YOU WILL NOT BE EXAMINED ON THIS .

Is this compound chiral? If so, is it R or S?

Enantiomers can be described as (+)/(-)

In addition to R/S, you will encounter molecules labelled as
(+)/(-).
Whereas R/S is based on geometry, (+)/(-) is based on a
physical property of chiral compounds:
Optical Activity: the ability to rotate plane-polarised light.
Two enantiomers will interact differently with polarised light,
scattering it in opposite directions.
(A bit like bowling to left-handed or right-handed batsmen)

Optical Rotation

The instrument that measures the angle of

rotation of plane-polarised light is called a
polarimeter.

In order to quantify the observed rotation,

, both the path length through the
sample and the concentration of the
sample need to be accounted for. The
specific rotation [ ] can be calculated by:

Figure
22.12a

20

Unlike R/S. this property changes with solvent, temperature, concentration and wavelength of light
used. Typical conditions are at 20C, in ethanol or chloroform with light of =589nm (e.g. sodium
lamp D-line).
is the observed rotation in degrees, c is the concentration in g/mL and l is the length of the
sample in dm (1dm=10cm=0.1m). These are bizarre units: the unit for [ ] is not normally stated.

Optical Rotation

The optical isomer that rotates plane-polarised light in

a clockwise direction is called dextrorotatory.

The optical isomer that rotates plane-polarised light in

an anticlockwise direction is called levorotatory.

Given the symbols (+)-isomer

Given the symbols (-)-isomer

An equal mix of (+) and (-) is known as a racemic

mixture or racemate.

Racemates have an observed rotation of 0o

Usually given the symbols dl or ()

Enantiomers can be L or D
To add to the alphabet soup, some compounds
are labelled L or D.
This is archaeic notation, from many years ago.
Before X-ray crystallography became
commonplace, chemists would work out the
detailed structure of compounds by breaking
them down into smaller pieces.
If a fragment resembled D-glyceraldehyde it
would be labelled D etc etc.
It is only commonly now used with amino acids
and sugars: all natural chiral amino acids are
called L-.

R/S/+/-/L/D what the ?

Knowing which enantiomer you have is IMPORTANT as they are

different molecules, so make sure you use the correct convention.
This is why Prelog was awarded a Nobel prize for systemising
this mess.

Ghana is to change over to driving on the right. The change will be

made gradually.

Life is chiral
substrate
(+)-lactic acid
m.p. = 53 C
[]D = +3.82

()-lactic acid
m.p. = 53 C
[]D = 3.82

CO2H
H3C

H
OH

CO2H
H
HO

Enzymes can
enantiomers.

CH3

(and

enzyme
(Nature's catalyst)
lactate
dehydrogenase

lactate
dehydrogenase

usually

do)

discriminate

product
CO2H
H3C

no reaction

between

They can do this because they are also chiral (and single
enantiomers) . We will discuss this more in a later lecture.

Racemates
CO2H
H3C

lactate
dehydrogenase

CO2H
H3C

H
OH

(1)

(S)-(+)-lactic acid

CO2H
H3C

CO2H

NaBH4
H3C

OH

(2)

no optical activity
() lactic acid

The chemical product (2) contains an equal mixture of either

enantiomer.
A mixture of 50:50 of two enantiomers is called a racemic
mixture, or racemate
Racemates have no optical activity: the rotation caused by one
enantiomer exactly cancels out that of the other.

Physical Properties of Enantiomers

(+)-lactic acid
m.p. = 53 C
[ ]D = +3.82

( )-lactic acid
m.p. = 53 C
[ ]D = 3.82

CO2H
H3C

H
OH

CO2H
H
HO

CO2H
H3C
OH
( ) lactic acid
m.p. = 17? C
no optical activity

CH3

It is important to know, if you are using a racemic mixture, an arbitrary mixture or an

enantiomerically pure compound for a particular purpose as their physical properties may
differ.

Chirality is important!
O

()-carvone
(spearmint)

(+)-carvone
(caraway)

(+)-limonene
(orange smell)

()-limonene
(lemon smell)

On this and following slides, make sure you can identify chiral centres and designate
them R/S.

Importance of Chirality
Chirality is of importance to organic chemistry for a number of
reasons:
Many reactions will produce mixtures of enantiomeric products
which may need to be separated.
CO2H
H3C

H
OH

CO2H
H
HO

CH3

Many compounds made by synthetic organic chemistry are

designed to interact with living beings (antiseptics,
antibiotics, drugs, cancer chemotherapeutics), and living
beings are chiral.

Chirality is important!
HO
HO

NH2

HO

CO2H

NH2
CO2H

HO

L-DOPA (S)

D-DOPA (R)

toxic
DOPA-decarboxylase

HO
HO

NH2

dopamine
- deficient in
Parkinson's disease

DOPA must be marketed as a single enantiomer, not a

racemate.

Enantiopurity is important!
Two enantiomers may exhibit different biological properties:
O
N

O
N

NH

(R)-Thalidomide

O
NH

(S)-Thalidomide

Racemate marketed as a palliative for morning sickness in the

1950s.
R enantiomer useful and harmless.
S enantiomer potent teratogen

Diastereomers
(diastereoisomers)

Enantiomers & Diastereomers

For a molecule with 1
stereocenter, 21 = 2
stereoisomers are
possible
It gets more
interesting with
combinations of chiral
centres:

For a molecule with 2 stereocenters, a

maximum of 22 = 4 stereoisomers are
possible:
O
* *
HOCH2-CH-CH-CH
OH OH

2,3,4-Trihydroxybutanal

CHO

CHO

OH HO

OH HO

CH2OH

CH2 OH

Apairofenantiomers
(Erythrose)

CHO

CHO

OH HO

HO

OH

CH2 OH

CH2 OH

Apairofenantiomers
(Threose)

2 = 4 stereoisomers
2

O
* *
HOCH2 -CH-CH-CH
OH OH
R

CHO

CHO

OH HO

OH HO

CH2OH

CH2 OH

Apairofenantiomers
(Erythrose)

CHO

CHO

OH HO

HO

OH

CH2 OH

CH2 OH

Apairofenantiomers
(Threose)

Meso Compounds
Meso compound: an achiral compound
possessing two or more stereocenters
E.g. tartaric acid
R

COOH

OH HO

OH HO

OH HO

HO

OH

COOH

COOH

COOH

Amesocompound
(planeofsymmetry)

COOH

COOH

S COOH

H
S

COOH

Apairofenantiomers

m.p.=147C

m.p.=173 C

m.p.=173 C

[ ] = 0

[ ] = +12.7

[ ] = -12.7

Meso Compounds
Tartaric acid has two stereocenters
2n = 4, but only three stereoisomers exist

Meso Compounds
The RS and SR compounds are identical meso compounds

Summary

Cyclic Molecules
2-Methylcyclopentanol
2 stereocenters; a maximum of 4
stereoisomers
how many exist?
CH3

H3 C

OH
HO
cis2Methylcyclopentanol

CH3

H3 C

OH
HO
trans2Methylcyclopentanol

Cyclic Molecules
1,2-Cyclopentanediol
2 stereocenters = a maximum of 4
stereoisomers
how many exist?
OH

HO

OH HO
cis1,2Cyclopentanediol

OH

HO

OH
HO
trans1,2Cyclopentanediol

Cyclic Molecules
4-Methylcyclohexanol
how many stereoisomers are possible?
H3C

OH

cis4Methylcyclohexanol

H3 C

OH

trans4Methylcyclohexanol

Three Or More Stereocenters

how many stereocenters are present in the
molecule on the left?
how many stereoisomers are possible?
one of the possible stereoisomers is menthol
assign an R or S configuration to each
stereocenter in menthol

OH
2Isopropyl5methyl
cyclohexanol

OH
Menthol

Three Or More Stereocentres

Cholesterol
on the left is the carbon skeleton of
cholesterol
how many stereocentres are present?
how many stereoisomers are possible?
H

H
H
HO
Thecarbonskeletonof
cholesterol

HO
Thisisthestereoisomerfoundin
humanmetabolism

Thiostrepton 2

16

Thiostrepton is an antibiotic compound produced by some

streptomycete bacteria.
Only one stereoisomer is produced:

DNA

DNA is chiral: there are deoxyribose sugars

in its structure:

A filament of duplex DNA has around 20

billion stereogenic centres per metre. (You
have ~2m DNA per cell and ~1013 cells in
your body)

Lactate Dehydrogenase
LDH is a protein found in
humans, composed of
around 330 chiral
aminoacids. Of 2330
possible stereoisomers,
only 1 is produced.

Lactate Dehydrogenase
O

H OH

NADH
CO2H

enzyme
(both enantiopure)

CO2H
S-(+)-lactic acid (only)

DEMO

Chemical Synthesis
attack of H from behind

NaBH4
CO2H

pyruvic acid

attack of H from in front

HO H
CO2H
lactic acid

H OH
+

CO2H
lactic acid

Chirality in the Biological World

because enzymes are chiral substances, most either produce or react with
only substances that match their stereochemical requirements

Schematic diagram of the surface of an enzyme capable of distinguishing

between enantiomers

Virus Particle
This virus particle is made
up from around 400 copies
of a protein, which is itself
made up of 100s of chiral
aminoacids.
Of ~210,000 stereoisomers,
only one exists.

http://www.stanford.edu/group/virus/polyoma/2005/SV40%20Large.jpg

You need to
Appreciate all forms of isomerism: Constitutional isomerism, Stereoisomerism
Chirality and enantiomerism:
be able to recognise chiral and achiral molecules and stereogenic centres
Represent enantiomers.
Be able to assign absolute configuration (R/S).
Appreciate optical activity and the lack of it with achiral compounds and racemic
mixtures. Do calculations of optical activity measurements.
Be able to recognise diastereomers and meso compounds.
Understand the importance of configuration to biological activity.
Look in Brown & LeMay and MasteringChemistry for plenty of example
questions.
Look in any Organic chemistry text for a compound and see if you can
determine its stereochemistry.

Problems
Draw a constitutional
isomer and a
stereoisomer of this
compound

Problems
How many
stereogenic centres
do each of these
compounds have?
Assign R or S to
them.

(a)

H Cl

H
OH

(b)

O
(c)

ONH3 +

Problems
Are these compounds
(B) isomers?
(C) Stereoisomers?
(D) A pair of enantiomers?
(E) Chiral?
(F) Diastereomers?
(G)Optically active?

Problems
Assign R/S to these compounds: