DUNCANRIG SECONDARY ADVANCED HIGHER CHEMISTRY

UNIT TWO

BOOKLET 5 Stereoisomers

and

Medicines

This section will involve expanding your knowledge of different types of

ISOMERS.

Isomerism arises whenever there is more than

one way to organise a given number of atoms.

It is very common in organic chemistry.

Note that when talking about isomers

always refer to two or more

molecules. One molecule is not an

isomer by itself but can be an isomer

of one or more other molecules.

Up to this point at both National 5 and

Higher chemistry levels only structural

isomers have been discussed.

These two compounds are structural isomers,

they have the same molecular formula {C2H6O} but a different structural

formula – isomers do not need to belong to the same chemical family.

Structural isomers

differ in terms of the

order in which the

atoms in the molecule

are joined together.

Skeletal formula can make structural isomers easy to spot.

1 Excluding compounds with ringed structures, how many structural isomers do the

following compounds have?

a. C3H8 b. C4H8 c. C3H6O d. C3H6O2

2. Consider the pairs of molecules shown below.

(i) State the name of both molecules in (a)

(ii) Draw the skeletal formula for both

molecules in (c)

(iii) State which pairs, if any, are structural

isomers.

(iv) Draw the skeletal formula of a structural

isomer of the left hand molecule in (b)

3. Which of the following is an isomer of

a. hex-3-ene b. 2-methylpentane c. 3-methyl hex-2-ene

d. hexane e. 2,3-dimethylbutane f. cyclohexane

4. Draw all the structural isomers of the haloalkane C3H6Cl2.

5. Which, if any, of the following compounds are structural isomers?

F

F

F

FHF

HH F

HF

H H

F

CH3CH2CH2NH2 (CH3)3N

and

and

and

(a)

(b)

(c)

In stereoisomerism, the molecules have the same molecular formula and the

same structural formula {the atoms are connected in the same order in each

molecule}. However, in each molecule, the atoms have a different three

dimensional arrangement in space which makes them non-superimposable.

This means that no matter how you twist and turn the molecules, one isomer

cannot fit exactly on top of the other.

Geometric isomerism or cis/trans isomerism arises when there is restricted

rotation somewhere in a molecule. This usually happens if there is a carbon to

carbon double bond or the carbon atoms are in a ring type structure.

Consider the molecule 1,2-dichloroethane.

These two models represent exactly the

same molecule. You can get from one to

the other just by twisting around the

carbon-carbon single bond. These

molecules are not isomers.

If you draw a structural formula instead of

using models, you have to bear in mind the

possibility of this free rotation about

single bonds. You must accept that these

two structures represent the molecule.

Now consider 1,2-dichloroethene

These two molecules aren't the same.

The carbon-carbon double bond won't rotate

and so you would have to take the models to

pieces in order to convert one structure into the other one. That is a simple

test for isomers. If you have to take a model to pieces to convert it into

another one, then you've got isomers. If you merely have to twist it a bit, then

you haven’t!

Drawing structural formulae for the last pair of models gives two possible

isomers.

In one, the two chlorine atoms are locked

on opposite sides of the double bond.

This is known as the trans isomer.

(trans : from latin meaning "across"

as in transatlantic).

In the other, the two chlorine atoms are locked on the same side of the

double bond. This is known as the cis isomer. (cis : from latin meaning "on this

side")

Geometric isomerism can also occur when carbon atoms are joined in rings.

More examples of geometric isomers.

Three important points.

It's very easy to miss geometric isomers in exams if they are drawn in a

certain way.

For example CH3CH=CHCH3 does not reveal the cis or trans nature

possible in this molecule.

Drawing the molecule like this

clearly shows that this is the trans isomer. If there is even the slightest

hint in a question that isomers might be involved, always draw compounds

containing carbon-carbon double bonds showing the correct bond angles

(120°) around the carbon atoms at the ends of the bond.

Not all molecules with a C=C will exhibit geometric isomerism.

Consider but-1-ene.

If the same atom or group of atoms exists on one side of the C=C

geometric isomers are not possible.

Geometric isomers are different compounds and as such they have different

properties like melting point, boiling point and solubility. This is usually due to the

overall polarity of the molecule or the way the shape dictates how the molecules will

pack together.

Cis-isomers tend to have higher boiling points than their trans counterparts as the

cis-isomer is usually more polar. Cis-isomers tend to have lower melting points and

lower densities than their trans counterparts as the “U” shape of the cis-isomer does

not pack together as well as the more linear shape of the trans-isomer

1. Draw structures and name the two geometric isomers of the following molecules.

a. 1,2-dibromocyclopentane b. hex-3-ene c. 4,4-dimethylpent-2-ene

2. The following molecules are all isomers of pentene. Which of them can exist as two

different geometric isomers.

3. Draw all the isomers, both structural and geometric, of C2H2Br2.

4. Draw a representation of the other geometric isomer for the molecule shown below.

Explain which of the two isomers will have the higher boiling

point

5. Compounds of formula C4H7Cl can exhibit geometric isomerism. Draw two structures

which confirms this statement.

6. The molecule phenylethene has a carbon to

carbon double bond yet it has no geometric

isomers.

Explain why this is the case.

7. Two geometric isomers of butanedioic acid are shown below.

a. Which of these isomers is the trans isomer?

b. Isomer (a) can form an intramolecular hydrogen

bond. Draw a dotted line on this isomer to show

the hydrogen bond.

c. Explain why isomer (b) has the higher melting

point.

(a) (b)

(d) (c) (e)

phenylethene

(a) (b)

Optical isomers are another type of stereoisomer. This type of stereoisomerism

arises whenever a molecule contains an ASYMMETRIC carbon atom sometimes

called a CHIRAL carbon atom.

A chiral carbon atom will have four different groups

attached to it.

When a molecule has an asymmetric carbon there

will be two possible arrangements of the atoms.

The only difference between these will be that one

is a MIRROR IMAGE of the other and the mirror images will not be

superimposable on each other – no matter how the molecule is rotated.

The optical isomers are said to be CHIRAL

(from the Greek for hand) – your hands

are also chiral objects.

The two optical isomers are called

ENANTIOMERS (from the Greek for opposite)

C

BrH

CH3CH

2

CH3

C

BrH

CH3CH

2

CH3

2-bromobutane CH3CH2CHBrCH3

butan-2-ol CH3CH2CH(OH)CH3

With optical isomerism, there is no difference in connectivity and no double

bonds. The isomerism is to do with the arrangement of the atoms in space. It

arises through the presence of a chiral centre. Optical isomers are non -

superimposable mirror images of each other; a set of optical isomers are called

enantiomers.

Due to the fact that a chiral carbon atom must have four different groups

attached to it, enantiomers are most easy recognised if the molecules is

drawn with the asymmetric carbon at the centre of a tetrahedron.

A common question in the exam will present

you with one enantiomer and ask you to

draw the other enantiomer.

Consider the two enantiomers shown

on the right.

One enantiomer can always be changed into the other by swapping ANY TWO

of the groups attached to the asymmetric carbon atom.

Another common question will ask you to identify the chiral carbon atom in

what can seem a daunting molecule.

To identify a chiral carbon atom look for any carbon atom with FOUR

DIFFERENT groups attached.

The chiral carbon atoms in these three

molecules have been circled.

It is useful to remember that a carbon

atom connected to a multiple bond or in a

benzene ring type compound can NEVER

be chiral.

Unlike geometric and structural isomers, physical properties

like melting points, boiling points and solubility are identical

for a set of optical isomers(enantiomers).

Optical isomers do differ however in two important ways.

Light is a form of electromagnetic radiation and is most simply understood as a

wave phenomenon. A normal ray of light consists of waves vibrating in many

directions. Certain substances only(transmit) allow light vibrating in a single

plane to pass through them, blocking out(absorbing) all others. Passing light

through such a substance produces PLANE POLARISED LIGHT. Some

sunglasses make use of this to reduce glare and reflections.

The diagram shows an instrument called a POLARIMETER. This device creates

plane-polarised light by passing normal light through a polarising filter. The

plane-polarised light is passed through a solution containing an optical isomer

which will interact with the light and cause the plane to be rotated. If,for

example, one enantiomer rotates the plane clockwise through X degrees, the

other enantiomer will rotate the plane anti-clockwise through X degrees. If a

mixture contains an equal amount of both enantiomers no rotation is observed.

Such a mixture is termed a RACEMIC MIXTURE.

The optical isomers of limonene. One

would cause rotation of x degrees to

the left while the other would cause

rotation of x degrees to the right.

One isomer causes orange flavour,

the other lemon.

The vast majority of molecules in living systems are chiral.

Although these molecules can exist as a number of stereoisomers, generally

only one is produced and used in a given biological system.

Consider chymotrypsin, a protein-digesting enzyme in the digestive system of

animals. Chymotrypsin contains 251 chiral centers - the maximum number of

stereoisomers possible is 2251 - there are only 238 stars in our galaxy!

Enzymes are like hands in a handshake (lock and key) the substrate fits into a

binding site on the enzyme surface. A left-handed molecule will only fit into a

left-handed binding site and a right-handed molecule will only fit into a right-

handed binding site. Enantiomers have different physiological properties

because of the handedness of their interactions with other chiral molecules in

living systems.

Around 50 years ago pregnant women were offered a new wonder drug called

thalidomide to relieve the morning sickness associated with pregnancy

Unfortunately the drug was sold as a

50:50 racemic mixture. One enantiomer

alleviated morning sickness, the other

caused terrible birth defects.

1 2-aminopropanoic acid (alanine) has two enantiomers (optical isomers) because it has a

chiral molecule containing an asymmetric carbon atom. One enantiomer is a

non-superimposable mirror image of the other.

a. Draw the structures of the two enantiomers.

Use your diagram to explain what is meant by the term

non-superimposable mirror image.

b. Explain what is meant by a chiral molecule and say how you

would recognise an asymmetric carbon atom.

c. Why doesn't a racemic mixture of alanine have any effect on the plane of polarisation

of plane polarised light?

2. Which of the following molecules display optical activity?

a. CH2OHCH2OH b. CH3CHClCOOH c. CH2=CHCl

3. Name the alkane with fewest number of carbon atoms which exhibits optical activity.

4. Which of the following best describes the relationship between the following two

structures?

a. They are the same

b. They are enantiomers

c. They are geometric isomers

d. They are structural isomers

5. Draw the full structural formula for 2-chloro-2-methylpentane

Does this molecule exhibit optical isomerism?

6. The skeletal structure of the hormone testosterone is shown below

a. Write the molecular formula for testosterone.

b. Will testosterone react with bromine water?

c. Circle any asymmetric carbon atom in testosterone.

C CH2 C H

H

CH3

H

H

CH2CH3

C CH2 C H

H

CH3

H

H

CH3CH2

6. Consider the compounds, 1-chloropentane, 2-chloropentane and 3-chloropentane.

a. Which of these compounds can exhibit optical isomerism?

b. Draw the two enantiomers of this compound.

c. How could these two enantiomers be distinguished experimentally?

7. Three cyclic compounds are shown below

Circle any asymmetric carbon atom in these compounds.

8. Which of these amino acids does

not have an asymmetric carbon atom?

CH3

CH3

CH3

9. Consider the molecules in the grid below.

a. Which two boxes contain a pair of

geometric isomers?

b. Which type of isomerism is

exhibited by molecules B and C?

c. Explain why molecules C and D are

not isomers?

10. Consider the molecules in the grid below.

a. State the names of all four compounds.

b. Which molecules exhibit geometric

isomerism.

c. Which molecules would rotate plane

polarised light?.

11. Consider the molecules in the grid below.

a. Name and draw the structures of the

geometric isomers of molecule C?

b. Which molecule is LEAST polar?

c. Explain why molecules B and D do not have

geometric isomers.

Naturally occurring human proteins are polymers made from amino acids. As

mentioned earlier in this section protein molecules are chiral. Receptor sites

are also chiral and so only the correct optical isomer(enantiomer) will be

biologically active.

The left hand enantiomer (an amino acid)

will fit into the receptor as it has the

correct groups in the proper positions.

If this were an agonist the medicine

would enable the receptor to function

correctly.

If it were an antagonist it would still fit

but would not activate a response in the

cell. In addition if it binds strongly it will

prevent a natural molecule triggering the

cell.

Heroin, and all opiates, have a chemical structure similar to endorphins, a class

of chemicals present in the brain. Endorphins are naturally manufactured in

the brain to provide relief when the body experiences pain or stress. They may

even produce euphoria. When someone takes morphine or heroin, the molecule

binds to the endorphin-receptor sites on neurons in the brain, and mimics the

function of natural endorphins.

All these drugs behave in a similar manner as they have the same pharmacophore. Chemists

can manipulate the basic structure to make the drug more efficient but have less side

effects. These drugs are agonists. The morphine pharmacophore is highlighted.

Remember an agonist will bind to a receptor and stimulate the natural response of the cell

and an antagonist will also bind to a receptor but it blocks the natural cell response.

The main symptoms of asthma are breathlessness and wheezing which are caused

by a narrowing of the air passages in the lungs. Attacks are relieved naturally when the

body releases adrenaline to widen the airways.

Attacks are relieved naturally when the body releases

adrenaline to widen the airways.

Adrenaline cannot be given to treat asthma as it has

undesirable side effects such as increased heart rate.

The drug salbutamol (sold as ventolin) is commonly used

to treat asthma. It is an agonist with the same

pharmacophore as adrenalin but without the side effects.

High Blood Pressure, Stroke, Heart Attack

Propranolol is one of many drugs used to treat high blood pressure which is caused by an

increased output of blood from the heart or by an increased resistance to blood flow in the

arteries. Adrenaline is involved

again as it is the

natural molecule which

increases blood pressure.

One way to lower this is

to block the

beta-receptors which trigger the increase. Propranolol is a beta-blocker antagonist.

1. Aspirin and paracetamol act on pain by occupying the enzyme site needed to make the

prostaglandins which are produced in response to injury.

Explain whether aspirin and paracetamol are agonist or antagonists.

2. Isoprenaline and salbutamol are both used in the treatment of asthma as they help relax

airways in a similar manner to the body’s natural compound adrenalin

Use your knowledge of chemistry to comment on the structural features of these

molecules and how they act as asthma drugs.

3. The table shows the structural formulae of some sulphonamides and their antibacterial

activity.

Which of the following would be an active antibacterial agent?

5. Chemists are developing medicianl compounds which block the ability of certain

bacteria to bind to the surface of cells. This will help stop the spread of infection.

a. What term is used to describe medicinal compounds which act in this way?

b. What name is given to the structural fragment of this type of medicinal compound

which binds to a receptor?

c. The diagram shows the structure of four of these compounds.

Draw the structural fragment which is common to these compounds which allows them

to bind to the relevant receptor.

6. Lactic acid in the form of lactate ions is dehydrogenated in the liver by the enzyme,

lactate dehydrogenase.

The diagram shows how one of the optical isomers of the lactate ion binds to an active

site of lactate dehydrogenase.

a. Which type of intermolecular force is involved when the methyl group of the lactate

ion binds to the hydrophobic region of the active site?

b. Draw a structure for the other optical isomer of the lactate ion.

c. Explain why this other optical isomer of the lactate ion cannot bind as efficiently to

the active site of lactate dehydrogenase.

7. The active structural fragment of several

pain-killing molecules is shown

What term best describes this structural fragment?

A agonist B pharmacophore C antagonist D receptor

8. Antihistamines act by inhibiting the action of the inflammatory agent histamine in the

body.

Antihistamines can be described as

A agonists B pharmacophores C antagonists D receptors

9. Propoxyphene is a pain-killing drug. Its structure is shown below.

a. Draw the skeletal formula for propoxyphene.

b. There are two asymmetric carbon atoms in propoxyphene.

Referring to the structure above, identify both asymmetric carbon atoms.

c. Propoxyphene has a pharmacophore which binds to specific receptors.

What is meant by the term pharmacophore?

d. Propoxyphene stimulates the body’s own natural response to pain.

What term is used to describe medicines which act in this way?

e. Propoxyphene is normally prescribed as the salt propoxyphene hydrochloride.

Which atom in propoxyphene is likely to react with hydrochloric acid to produce

this salt.