Topic 19

AMINO ACIDS, POLYMERS, ORGANIC SYNTHESIS AND

BIOCHEMISTRY

Amino Acids
Polymers and Proteins
Biochemistry
Organic Synthesis
 STRUCTURE OF AMINO ACIDS

Amino acids are molecules containing an amine group and a carboxylic acid group.
Naturally occurring amino acids have the following general formula:

There is a central carbon atom attached to a hydrogen, a carboxylic acid group, an amine
group and an alkyl group. Amino acids are thus all chiral except for glycine, in which the
R is another H atom.

Amino acids occur widely in nature and have a number of uses in the human body. Some
simple examples are:

glycine alanine
aminoethanoic acid 2-aminopropanoic acid
 ACID-BASE PROPERTIES OF AMINO ACIDS

Carboxylic acids have acidic properties and react with bases.

Amines have basic properties and react with acids.
It therefore follows that amino acids have both acidic and basic properties.

i) reaction with bases

Amino acids react with strong bases such as sodium hydroxide:

In high pH, therefore, amino acids exist in anionic form:

ii) reaction with acids

Amino acids react with strong acids such as hydrochloric acid:

H Cl
-
H H H H

N N+
O O

R R
C C
+ HCl
C C
OH
OH
H H

In low pH, therefore, amino acids exist in cationic form:

H
H H
N
+ O

R C C
OH
H
iii) reaction with itself

Since amino acids have a proton donating group and a proton accepting group on the
same molecule, it follows that each molecule can undergo an acid-base reaction with
itself:
H
H H
H H N
N
+ O
O
R C C
R C C -
O
OH H
H

The double ion that is formed as a result of this reaction is called a Zwitterion. This
reaction happens in the solid state.

In the solid state, therefore, amino acids are ionic. This explains why they are solids with
a high melting point.

iv) summary

Amino acids can exist in molecular form, in cationic form, in anionic form or in
Zwitterion form depending on the environment:

H
H H
N
+ O

R C C
-
O
H

in neutral solution in alkaline solution in acidic solution in the solid state

Since amino acids can react with acids and alkalis, they make very effective buffer
solutions.
 POLYMERS

1. Making Addition Polymers

Addition polymers are formed from alkenes.

Alkenes can be made to join together in the presence of high pressure and a suitable
catalyst. The π-bond breaks and the molecules join together. No other product is formed,
and so this is known as addition polymerisation. Since the polymers are made from
alkenes they are also known as polyalkenes.

ethene  polyethene

The product of this addition process is a very long hydrocarbon chain.

Addition polymers can be made from any alkene:

Eg propene poly(propene)

Eg but-2-ene poly(but-2-ene)
Many useful polymers are addition polymers made by this process:

 polyethene is used in plastic bags and in crates

 polypropene is used in plastic tubing

 polychloroethene (polyvinylchloride) is used in waterproof clothing and records

 polyphenylethene (polystyrene) is used in packaging

The most favourable conditions for the polymerisation of alkenes can be deduced from
Le Chatelier's principle, if two points are noted:
- the reaction involves breaking -bonds only, and many -bonds are made. The
reaction is thus exothermic.
- The reaction involves a reduction in the total number of moles:

Since the reaction is exothermic, the best yield is obtained at low temperature. Since the
number of gas moles decreases, the best yield is obtained at high pressure.

Addition polymerisation reactions are carried out at high pressure in the presence of a
suitable catalyst.
2. Making Condensation Polymers

(i) Polyesters

It has been shown that if a carboxylic acid is reacted with an alcohol, then an ester is
formed and a small molecule is lost.

Eg ethanoic acid + ethanol  ethyl ethanoate + H2O

Eg benzoic acid + methanol  methyl benzoate + H2O

These are examples of condensation reactions – combination of two or more molecules

followed by the elimination of a small molecule.

It follows that if a dicarboxylic acid is reacted with a diol, then the -COOH group at each
end of the dicarboxylic acid should join to an -OH group, and the -OH group at each end
of the diol should join to a -COOH group. It should therefore be possible for all the
molecules to link together and form a polymer.

Eg benzene-1,4-dicarboxylic acid and ethan-1,2-diol

benzene-1,4-dicarboxylic acid ethan-1,2-diol

These two compounds can link together to form a polymer, and water is given off:
This polymer can be represented by the following repeating unit:

The overall equation can be represented as:

The monomer units are linked together by the ester group:

Polymers containing this type of linkage are therefore known as polyesters.

The above polymer is known as terylene. It is used in fire-resistant clothing (eg racing
drivers)

Another example of polyester formation is:

Ethanedioic acid and propan-1,2-diol

 (ii) Polyamides

It has been shown that if a carboxylic acid is reacted with a primary amine, an N-
substituted amide is formed:

Eg propanoic acid + ethylamine == N-ethylpropanamide + H2O

It follows that if a dicarboxylic acid is reacted with a diamine, the -COOH group at each
end of the dicarboxylic acid with join to an -NH2 group, and the -NH2 group at each end
of the diamine will join to a -COOH group. It should therefore be possible for each of the
molecules to join together and form a polymer.

Eg hexanedioic acid + 1,6-diaminohexane

These two compounds can link together to form a polymer, and water is given off.

The polymer can be represented by the following repeating unit:

The overall equation can be represented as:

The monomers are linked together by the amide, or peptide link:

Polymers containing this type of linkage are therefore known as polyamides.

The above polymer is known as nylon 66. It is a man-made fibre used in clothing

Another example of polyamide formation is:

Butanedioic diacid and 1,2 diaminopropane

(iii) Proteins

Amines undergo condensation reactions with carboxylic acids.

Since amino acids have both acid and amine groups, two molecules can therefore react
with each other to form a molecule containing a peptide or amide link:

This reaction is a condensation reaction and the resulting molecule is called a dipeptide.

Dipeptides can also be formed by the condensation of two different amino acids. In this
case two different molecules can be formed:
 or

Since the resulting dipeptides also have both amine groups and carboxylic acid groups,
they can undergo further condensation reactions, eventually forming polymers:

This reaction is carried out alongside DNA molecules in the bodies of living organisms.
The DNA lines up the amino acid molecules in the correct order so that the condensation
reactions can take place. The resulting polymer is called a protein, and is an essential
component of living organisms.

Polyesters, polyamides and proteins are collectively known as condensation polymers

because they are the product of condensation reactions.
3. Properties of Polymers

i) Addition Polymers

Addition polymers (polyalkenes) are long chain hydrocarbons which are saturated and
non-polar. Their structure results in their having a number of characteristic properties:

a) Since the hydrocarbon chains are often very long, the Van der Waal's forces between
the chains are often very strong and the polymers have relatively high melting and
boiling points. Since the chain length is variable, most polymers contain chains of a
variety of different lengths. Thus the Van der Waal's forces are of variable strength
and these polymers tend to melt gradually over a range of temperatures rather than
sharply at a fixed temperature. As the chains are not rigidly held in place by each
other, polymers tend to be reasonably soft.

b) Since the chains are non-polar, addition polymers are insoluble in water. In fact the
long saturated hydrocarbon chains result in polyalkenes being very unreactive
generally, as they cannot react with electrophiles, nucleophiles or undergo addition
reactions.

This results in their widespread use as inert materials - they are very useful as
insulators, as packaging and in making containers.

However their low reactivity means that they are not easily decomposed in nature and
as a result have a very long lifetime. Such substances are said to be non-
biodegradable, and constitute an environmental hazard as they are very persistent in
nature and thus difficult to dispose of.

ii) Condensation polymers

Condensation polymers (polyesters, polyamides and proteins) consist of long chains

which include polar bonds (C-O and C-N). This gives condensation polymers certain
characteristic properties

a) The strength of the intermolecular forces between the different chains in

polyamides and proteins is enhanced by the presence of hydrogen bonding.
Polyamides are therefore generally very strong. In some natural polyamides, such as
proteins, intramolecular hydrogen bonding is possible and the molecule curls up to form a
helical structure:

Polyamides and polyesters are both used largely in high-strength synthetic fibres.

Polyesters are used as wool and cotton substitutes in clothing (esp jumpers, T-shirts,
shirts etc) and also in carpets and rugs. Bullet-proof vests and some flame-retardant
clothing are made from polyesters.

Polyamides are more elastic and used in underwear, fishing nets and other synthetic
fibres.

b) Because condensation polymers are made up of chains containing polar bonds, the
polar carbon atoms can be readily attacked by nucleophiles and as a result the
polymers can be broken up and the constituent monomers reformed.
Condensation polymers are hence biodegradable, and so clearly constitute a
smaller environmental hazard than addition polymers, whose chains are made up
entirely of non-polar C-C bonds and which are hence non-biodegradable.

The break-up of these polymers is carried out in aqueous solution and can be classed as
hydrolysis reactions:

Polyesters are best hydrolysed in strongly alkaline conditions, in which they undergo
saponification to produce the salt of the carboxylic acid:

Polyamides and proteins are best hydrolysed in strongly acidic conditions to give the
ammonium salt of the amine:
The hydrolysis of proteins breaks them down into their constituent amino acids; 6 moldm-
3
HCl is generally used.

This hydrolysis reaction enables chemists to deduce which amino acids are present in a
sample of protein.

The biodegradability of condensation polymers may compromise their effectiveness,

since physical and chemical durability is one of the reasons for their widespread use. A
balance must be struck between practical durability and long-term biodegradability.
4. Disposal and Recyling of Polymers

The disposal of non-biodegradable polymers is a significant problem. There are three

options:
- burying in landfill sites
This is widespread in all developed countries but is a completely unsustainable
practice, as each landfill site will eventually fill up. Landfill sites are also unsightly
and unhygienic.
- burning
This is also common, but burning polymers releases greenhouses gases such as
carbon dioxide and can also release toxic gases, depending on exactly what polymer
is being burned
- recycling
This is environmentally preferable to burying or burning, but it is not easy. Different
plastics need to be collected, separated and cleaned. They then need to be melted
down before being recast into the new item. Often this process can cost more than it
costs to manufacture the plastic from crude oil.
Some plastics cannot be melted – they burn or harden instead of melting. It is even
more difficult to recycle these plastics as they can only be used in the same shape in
which they were originally cast.

The above problems mean that the continued manufacture of non-biodegradable

polymers is a cause for environmental concern.

Biodegradable polymers decompose naturally, so burying them is slightly less

environmentally unsustainable as they will eventually break down.
They can be recycled, broken down into their original components and reused, but they
still need to be collected, separated and cleaned.
 BIOCHEMISTRY

1. Primary structure of proteins

The sequence of amino acids in a protein is known as the primary structure of the
protein. It varies from protein to protein, depending on the function that the protein needs
to perform.

Eg: gly – ala – leu – iso – gln

(each of these three–letter symbols is the code for an amino acid)
A protein can have several thousand amino acids, all arranged in a specific order.
The primary structure of a protein is generally stable as the amino acids are held together
by strong covalent bonds.

2. Secondary structure of proteins

Protein molecules are not straight as hydrogen bonds can form between amino acids on
the same chain or adjacent chains. The hydrogen atom on one peptide link can form a
hydrogen bond with the nitrogen or oxygen atoms on another peptide link, either on the
same molecule or on an adjacent molecule.

This can have one of two effects:

(i) α-helix

The structure coils up into a helical shape (this is known as an α-helix). Typically,
eighteen amino acids make five coils.
 (ii) β-pleated sheet

Alternatively, the hydrogen bonds can form predominantly between adjacent protein
molecules, resulting in a pleated sheet structure extending over 3 – 10 amino acids.

This short-range three-dimensional shape of a protein (covering a small number of

adjacent amino acids) is known as the secondary structure of the protein, and it is
generally either an α-helix or a β-pleated sheet.

3. tertiary structure of proteins

The tertiary structure of proteins describes the interaction between different amino acids
which are much further apart on the chain. These interactions control the overall shape of
the protein. There are three types of interaction that can take place between amino acid
groups and hence determine the tertiary structure of the protein.

(i) Hydrogen bonding – this is the same type of bonding as that which
determines the secondary structure of the protein; an attraction between the
hydrogen atom on one peptide link can form a hydrogen bond with the
nitrogen or oxygen atoms on another peptide link.

(ii) Ionic bonding – some amino acids contain the -NH3+ group and other
amino acids contain the -COO- group; these two groups can form an ionic
bond with each other.

(iii) Covalent bonding – cysteine contains a -CH2SH group; in the presence of

oxygen, these two groups can join together to form a S-S bond:
-CH2SH + -CH2SH + [O]  -CH2S-SCH2- + H2O

When these bonds form between amino acids which are not close to each other on the
chain, the influence the overall shape of the protein and are said to be part of its tertiary
structure.
 4. DNA (deoxyribonucleic acid)

DNA is the material from which chromosomes (and hence genes) are made. It is found in
the nucleus of all cells. DNA is a polymer made from monomers called nucleotides.

(i) Nucleotides

A nucleotide is a molecule consisting of a phosphate group (-H2PO4) bonded to a

deoxyribose sugar group (-C5H8O2-) which is turn bonded to a base group. There are four
different bases which the sugar group can be bonded to: Cytosine (C), Thymine (T),
Adenine (A) and Guanine (G). There are thus four different types of nucleotide, and all of
the structures are given in the AQA A-level Chemistry data sheet.

This is a nucleotide made from thymine:

 (ii) Polymerisation of nucleotides

A single strand of DNA forms when the nucleotides undergo condensation

polymerization; one of the -OH groups on the phosphate reacts with the -OH group on
the sugar of a different nucleotide and water is eliminated.

This process can continue indefinitely until a long chain is formed called a sugar-
phosphate backbone, with each sugar group also bonded to one of the base groups. This
is a single strand of DNA:
 (iii) Formation of double helix

DNA exists as two complementary strands. The bases pairs form hydrogen bonds with
base pairs on the complementary strand to form a double helix structure:

Adenine (A) always bonds with Guanine (G) and Cytosine (C) always bonds with
Guanine (G). This happens because each pair of bases has the correct complementary
shape to allow hydrogen bonding to take place:
 5. Anti-cancer drugs

Cisplatin is a drug which is well known for treating cancer. Cancer results from the
uncontrolled replication of certain cells in the body, and they replicate much faster than
healthy cells. They also have no Hayflick limit.

Cisplatin has the following structure:

Cisplatin works by binding to two different Guanine (G) base groups on a strand of DNA.
The cisplatin undergoes a ligand substitution reaction with each guanine – the N atom on
the guanine replaces the Cl atom on the cisplatin and a dative covalent bond is formed
between the Pt atom on cisplatin the N atoms on two different guanine groups:

This reaction prevents this section of DNA from replicating itself, as it is now unable to
create an RNA copy of itself, which makes transcription, and hence mitosis, impossible.
If the DNA is part of a cancerous cell, will prevent the multiplication of that cancerous
cell and prevent the spread of the cancer.

The disadvantage of cisplatin, as with many other anti-cancer drugs, is that it also binds
to DNA in healthy cells and prevents them from multiplying aswell. These drugs work
because cancer cells replicate faster than healthy cells, so the drugs have a greater effect
on cancerous cells. The worst side effects are seen in fast-replicating healthy cells such as
hair follicles, which is why people often lose their hair during cancer treatment.

When deciding whether or not to use a drug, it is necessary to evaluate the benefits of the
drug against its harmful side effects, and use the drug only if society considers that the
benefits of the drug significantly outweigh its harmful side-effects.

The best types of anti-cancer drug are those which can discriminate effectively between
cancerous cells and healthy cells.
 6. Enzymes

(i) How enzymes work

Enzymes are proteins designed to act as catalysts for specific reactions in Biochemistry.

Enzymes usually have globular shapes, with each globule having a crevice in it which is
known as the active site. The active site has the precise shape required to accommodate
the specific molecule or molecules it is designed to react with, known as the substrate
molecules. Because these crevices are three-dimensional spaces, they can usually only
catalyse an individual enantiomer of a chiral molecule. These enzymes are said to be
stereospecific.

(i) How enzyme-inhibiting drugs work

Drugs can be designed to prevent a harmful enzyme from catalyzing a harmful reaction.

Molecules can be created which have a similar shape to the substrate which the enzyme is
meant to be reacting with. These drugs mimick the substrates and bind to the active sites
instead, which prevents the substrate from bonding to the enzyme and prevents the
enzyme from catalyzing the reaction. This form of drug action is known as enzyme-
inhibition.

It is now possible to use computer modelling techniques to predict the shape of enzymes
and other proteins. Once the shape of an enzyme is understood, the shape of the substrate
required to react with the enzyme can also be predicted and inhibitors can be designed
accordingly.
 SUMMARY OF AMINO ACID AND POLYMER REACTIONS

Type of reaction Mechanism

1. acid-base reactions of amino acids

a) with acids
reagents: HCl
conditions: room temperature
equation: R-CH(NH2)-COOH + HCl  R-CH(NH3+Cl-)-COOH

b) with alkalis
reagents: NaOH
conditions: room temperature
equation: R-CH(NH2)-COOH + NaOH R-CH(NH2)-COO-Na+ + H2O
2. Polymerisation Reactions Free radical
a) Addition polymerisation (alkenes  polyalkenes) addition
(not
conditions: high temperature, Ziegle-Natte catalyst required)
equation:

b) Condensation polymerization - polyesters

Nucleophilic
dicarboxylic acid + diol  polyester addition-
conditions: H2SO4, heat under reflux elimination
equation:
(not
required)

c) Condensation polymerization – polyamides

Nucleophilic
dicarboxylic acid + diamine  polyamide addition-
conditions: warm, reflux elimination
equation:
(not
required)

Nucleophilic
d) Condensation polymerization - proteins
addition-
conditions: DNA elimination
equation: n R-CH(NH2)-COOH  H-(NHCRHCO)n-OH + (n-1) H2O (not
required)
3. Hydrolysis of condensation polymers

a) polyesters
reagents: NaOH(aq)
conditions: heat, reflux
equation:

b) polyamides
reagents: HCl(aq)
conditions: heat, reflux
equation:

c) proteins

reagents: 6 moldm-3 HCl

conditions: heat, reflux
equation: H-(NHCRHCO)n-OH + (n-1) H2O + n HCl  n R-CH(NH3+Cl-)-
COOH
 ORGANIC SYNTHESIS

It is possible to make a large number of organic products from a few starting compounds
and the necessary reagents. There are often many ways to make a particular molecule,
and when choosing the best pathway, chemists need to try to find:

(i) processes which do not require a solvent – solvents can be expensive,

difficult to dispose of and often cannot be re-used after a reaction
has taken place

(ii) processes which use non-hazardous starting materials – so that the

reactions are safer to operate and avoid having to dispose of any
unreacted starting materials

(iii) Processes which consist of as few steps as possible – this means they are
usually faster and more efficient

(iv) Processes which have a high atom economy – in order to avoid waste
products

The following organic pathways are required for A-level:

1. alkane  chloroalkane

reagents: chlorine
conditions: UV light
equation: CH4 + Cl2  CH3Cl + HCl (example)

NB This reaction introduces a new functional group onto the molecule

2. chloroalkane  alcohol

reagents: aqueous NaOH

conditions: warm, reflux
equation: R-Cl + NaOH  R-OH + NaCl

3. chloroalkane  alkene

reagents: alcoholic KOH

conditions: heat, distillation
equation: CH3CH2Cl + KOH  CH2=CH2 + KCl + H2O (example)
4. chloroalkane  nitrile

reagents: aqueous KCN

conditions: heat, reflux
equation: R-Cl + KCN  R-CN + KCl

NB This reaction introduces an extra carbon atom onto the molecule

5. chloroalkane  primary amine

reagents: excess ammonia

conditions: heat
equation: R-Cl + 2NH3  R-NH2 + NH4Cl

6. primary amine  secondary amine

reagents: chloroalkane
conditions: warm
equation: R1-NH2 + R2-Cl  R1R2NH + HCl

7. secondary amine  tertiary amine

reagents: chloroalkane
conditions: warm
equation: R1R2NH + R3-Cl  R1R2R3N + HCl

8. tertiary amine  quaternary ammonium salt

reagents: chloroalkane
conditions: warm
equation: R1R2R3N + R4-Cl  R1R2R3R4N+Cl-

9. alkene  dibromoalkane

reagents: bromine
conditions: room temperature
equation: CH2=CH2 + Br2  CH2BrCH2Br (example)

NB This reaction introduces a new functional group onto the molecule

10. alkene  bromoalkane

reagents: hydrogen bromide

conditions: room temperature
equation: CH2=CH2 + HBr  CH3CH2Br (example)
11. alkene  alkylhydrogensulphate

reagents: concentrated sulphuric acid

conditions: cold
equation: CH2=CH2 + H2SO4  CH3CH2OSO3H (example)

12. alkylhydrogensulphate  alcohol

reagents: water
conditions: warm
equation: CH3CH2OSO3H + H2O  CH3CH2OH + H2SO4 (example)

13. alkene  alcohol

reagents: steam
conditions: 300 oC, 600 kPa, phosphoric acid catalyst
equation: CH2=CH2 +H2O  CH3CH2OH

14. nitrile  primary amine

reagents: LiAlH4
conditions: dry ether
equation: R-CN + 4[H]  R-CH2NH2 (example)

15. alcohol  alkene

reagents: concentrated sulphuric acid

conditions: heat, reflux
equation: CH3CH2OH  CH2=CH2 + H2O (example)

16. primary or secondary alcohol  carbonyl

reagents: potassium dichromate and dilute sulphuric acid

conditions: warm, distillation
equation: R1R2CHOH + [O]  R1-COR2 + H2O

17. primary alcohol  carboxylic acid

reagents: potassium dichromate and dilute sulphuric acid

conditions: heat, reflux
equation: R-CH2OH + 2[O]  R-COOH + H2O
18. aldehyde  carboxylic acid

reagents: potassium dichromate and dilute sulphuric acid

conditions: heat, reflux
equation: R-CHO + [O]  R-COOH

19. carbonyl  alcohol

reagents: NaBH4(aq)
conditions: room temperature
equation: R1-COR2 + 2[H]  R1R2CHOH

20. carboxylic acid  carboxylate salt

reagents: NaOH
conditions: room temperature
equation: R-COOH + NaOH  R-COONa + HO

21. amine  alkylammonium salt

reagents: HCl(aq)
conditions: room temperature
equation: R1R2R3N + HCl  R1R2R3NHCl

22. carbonyl  hydroxynitrile

reagents: HCN
conditions: room temperature
equation: R1COR2 + HCN  R1R2COHCN

NB This reaction adds an extra carbon atom and introduces an extra functional
group onto the molecule

23. acyl chloride  carboxylic acid

reagents: water
conditions: room temperature
equation: R-COCl + H2O  R-COOH

24. acyl chloride  amide

reagents: ammonia
conditions: room temperature
equation: R-COCl + NH3  R-CONH2
25. acid anhydride  carboxylic acid

reagents: water
conditions: warm
equation: (RCO)2O + H2O  2R-COOH

26. acid anhydride  amide

reagents: ammonia
conditions: warm
equation: (RCO)2O + NH3  R-CONH2 + RCOOH

27. carboxylic acid + alcohol  ester

reagents: concentrated sulphuric acid

conditions: heat, reflux
equation: R1COOH + R2OH  R1COOR2 + H2O

28. acyl chloride + alcohol  ester

conditions: room temperature

equation: R1COCl + R2OH  R1COOR2 + HCl

29. acid anhydride + alcohol  ester

conditions: warm
equation: (R1CO)2O + R2OH  R1COOR2 + R1COOH

30. ester  carboxylic acid + alcohol

reagents: concentrated sulphuric acid

conditions: heat under reflux
equation: R1COOR2 + H2O  R1COOH + R2OH

31. ester  carboxylate salt + alcohol

reagents: NaOH(aq)
conditions: heat under reflux
equation: R1COOR2 + NaOH  R1COONa + R2OH

32. acyl chloride + primary amine  N-substituted amide

conditions: room temperature

equation: R1-COCl + 2R2-NH2  R1-CONHR2 + R2-NH3Cl
33. acid anhydride + primary amine  N-substituted amide

conditions: warm
equation: (R1CO)2O+ R2-NH2  R1-CONHR2 + R1-COOH

34. benzene  nitrobenzene

reagents: concentrated sulphuric and nitric acids

conditions: warm, reflux
equation: C6H6 + HNO3  C6H5NO2 + H2O

35. benzene  phenylalkanone

reagents: acyl chloride, AlCl3

conditions: room temperature
equation: C6H6 + RCOCl  C6H5COR + HCl

36. nitrobenzene  phenylamine

reagents: tin, concentrated HCl

conditions: room temperature
equation: C6H6 + 6[H]  C6H5NH2 + 2H2O
The interconversion of these compounds can be summarised in the following synthesis
maps:

a) aliphatic synthesis map – simple conversions

b) condensation reactions

c) aromatic conversions