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D.2 Aspirin & penicillin
Learning outcomes
 Understand the mode of action of aspirin
 Understand why aspirin is used
 Understand that ethanol has a synergistic effect with
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aspirin.
Understand how aspirin is synthesised from salicylic
acid
Understand how aspirin can be purified
Understand the characterisation of aspirin by melting
point and infrared spectroscopy
Understand how the chemical modification of aspirin
can affect its bioavailability
Analgesics
 Analgesics are common
pain relievers.
 Many analgesics also
have antipyretic
properties as well. They
can be used to reduce
fever
 Some analgesics are also
anti-inflammatory
drugs as well
Classification of Analgesics
Analgesics
Strong
Mild
Analgesics
Aspirin
Analgesics
Ibuprofen
Acetaminophen
Opium
Heroin
Codeine
Mild Analgesics
 Mild Analgesics include over-the-
counter pain relievers and fever
depressants.
 Examples of mild analgesics
include Aspirin, acetaminophen,
and ibuprofen
Aspirin
 Aspirin is a derivative of
salicyclic acid
 Salicyclic acid was found in the
bark of the willow tree and was
used as a pain reliever and as a
way to relieve fever symptoms
of malaria
Salicyclic Acid
Aspirin
Aspirin
 In 1899, Felix Hoffman, a chemist from the Bayer Company,
developed a low-cost process to synthesize an ethanoate ester
of salicyclic acid, called aspirin
 In the synthesis of Aspirin, the ethanoic acid forms an ester
with the alcohol group on the second carbon
Aspirin
 Aspirin is believed to
inhibit the enzyme,
Prostaglandin synthase
which is formed at the site
of an injury.
 This inhibits the
production of
prostaglandins which
produce fever and swelling
as well as transmitting pain
signals to the brain.
Aspirin
 Aspirin is able to reduce pain and fevers
and dilate blood vessels
 Aspirin enlarges blood vessels which helps
prevent blood clots.
 This vasodilation of the surface blood
vessels also allows an increase of heat
released which lowers the temperature of a
fever
 Aspirin is also taken to prevent
recurring heart attacks
 It may also be effective in
preventing prostrate cancer
Side Effects of Aspirin
 Aspirin can irritate the stomach lining which may
lead to ulcers
 If aspirin is used over long periods of time, it may
lead to problems with blood clotting
 An overdose on aspirin, such as the case with some
arthritis sufferers, may lead to dizziness, ringing in
the ears, gastrointestinal problems, mental
confusion, and bleeding.
 Some people are allergic to aspirin leading to
bronchial asthma
 In children under 12 Aspirin has been linked to
Reye’s syndrome
The synergistic effect of ethanol
 Synergism- two drugs taken together can have more
effect than sum of their individual effects
 Ethanol can increase the effect of other drugs, extra
care must be taken while prescribing medicine to
alcoholic person.
 When alcohol is taken with aspirin there is an
increased risk of hemorrhage (bleeding) in the
stomach.
Synthesis of Aspirin
The type of reaction is addition–elimination (the CH3CO group is
added to aspirin and ethanoic acid is eliminated) and happens in
the presence of a small amount of concentrated phosphoric (or
sulfuric) acid catalyst.
Lab synthesis
Alternate synthetic route for preparation of Aspirin involve
reacting ethanoyl chloride with salicylic acid
Example page 11
 D.1 In an experiment to synthesise aspirin, 5.60 g of
salicylic acid (Mr 138.13) was reacted with 8.00 cm3
ethanoic anhydride (density 1.08 g cm−3) in the
presence of a concentrated phosphoric acid catalyst.
5.21 g of a white solid was obtained at the end of the
reaction. Calculate:
 a which reagent was in excess
 b the yield of aspirin.
Purification of Aspirin
 Recrystallization
 The basic principles of recrystallization are that a solid
is dissolved in a solvent in which it is soluble at raised
temperatures but much less soluble at lower
temperatures. Any impurities are present in much
smaller amounts and so remain in solution at the lower
temperature.
The procedure for recrystallization is:
The product is dissolved in the minimum amount of
hot solvent to form a close-to-saturated solution.
2. The solution is filtered while still hot to remove any
insoluble impurities. Vacuum filtration is used
because it is much faster – the product may start to
crystallise while filtering if the solution cools too
much.
3. As the solution cools, the product becomes less
soluble in the solvent and comes out of solution as
solid crystals – less of the solid dissolves at lower
temperatures. It may be necessary to cool in ice or
scratch the inside of the beaker to initiate
crystallisation.
1.
4. Any solid product is separated from the solvent by
vacuum filtration.
5. Any impurities also dissolve in the hot solvent, but
because they are present in much smaller amounts
they do not exceed their solubility, even at lower
temperatures, and remain in solution. Aspirin can be
recrystallised from ethyl ethanoate or ethanol
6. (usually a 95% ethanol/water mixture). Water is
generally not used for recrystallisation because
aspirin tends to decompose in hot water.
Purity of Aspirin
Purity of Aspirin can be determined by
 Chromatography
 Melting point – The melting point of pure Aspirin is
reported between 138- 140 0C. If it does not melt in this
range it is considered to be impure.
IR Spectra of Aspirin
The Discovery of Penicillin
 Penicillin was discovered in 1929 by
scientist Alexander Fleming.
 He left for vacation with an agar
plate covered with the bacteria
Staphylococcus aureus.
 When he returned he noticed that
the fungus, Penicillium, had grown
on the plate

The bacteria colony
surrounding the fungus had
become transparent because
the bacterial cells had
undergone lysis.
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Development of Penicillin
 Several years later Howard Florey and
E.B. Chain stumbled across Fleming’s
research papers and were intrigued by
his findings.
 They were convinced that Flemming’s
discovery could save a lot of lives,
prevent pain, and make it much easier
to fight infectious diseases and prevent
other infections.
 They developed a way to mass produce
penicillin making it available to soldiers
wounded in world war II.
 Florey and Chain were awarded the
Nobel Prize in 1945 for their work on
penicillin.
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Penicillin Structure
Penicillins have a special structure that allows
them to interfere with the formation of the cell
wall when bacteria reproduce
The general structure of penicillin
Video
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How Does it Function?
 Penicillin prevents the cross linking of
small peptide chains in peptidoglycan,
which is the main polymer in bacterial
cell walls.
 They do not affect bacteria which already
exist, rather Penicillin’s affect the
synthesis of new bacteria.
 The new bacteria grow without the ability
to maintain cell rigidity, making them
susceptible to osmotic lysis.
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The Action of Penicillins
The amide group in the
beta lactam is more
reactive due to the
strained ring.
The structure of the
beta lactam is similar to
the structures of
cysteine and valine.
The beta lactam binds
to the enzyme that
synthesizes the cell wall
in bacteria, blocking its
action.
As a result the bacteria
rupture and break and
cannot reproduce.
Note the similarities in structure
to the beta lactam.
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Bacterial Immunity to
Penicillin
 Antibiotic Resistance –
Mutated bacteria which are
immune to antibiotics are
more likely to survive when
excessive antibacterials are
used.
 Bacteria develop enzymes
known as penicillinases that
destroy or render penicillin
ineffective.
 New antibiotics are
developed by changing the R
group side chain.
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Structure of Penicillin
Penicillin is a group of compounds which all contain the same
basic ring structure, known as beta-lactam. It is comprised of
two amino-acids (valine and cyteine) through a tripeptide
intermediate. The third amino acid (the R group) is replaced by
another group, which gives different characteristics to differing
penicillins.
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Narrow Range and Broad
Range Antibiotics
 Narrow range antibiotics target specific
kinds of bacteria. They are usually more potent.
 Broad range antibiotics are effective against a wide
range of bacteria.
 When doctors diagnose patients suspected of having
bacterial infections, they must first take samples of
body fluids, and try to determine the precise type of
infection.
 A broad range antibiotic might be prescribed initially.
Once a bacterial infection is properly diagnosed it may
be appropriate to switch to a narrow range antibiotic.
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Overuse of Penicillin
 Leads to greater immunity of bacteria to penicillin,
since the strongest and most resistant strains survive.
 Greater doses of penicillin are required to be effective
 Danger of developing super bacteria
 Kill beneficial bacteria as well as harmful bacteria
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Penicillin Synthesis
A sterilized growth
medium and an
inoculum of strongly
growing hyphae is
added to stainless steel
fermenters. The
fermenters stirred
continuously and
glucose, nitrate and
sterile air are
periodically added.
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 The first penicillin to be
isolated and purified was
penicillin G
(benzylpenicillin) However,
this penicillin has a number
of disadvantages, one of
which is that it is easily
broken down by stomach acid
and must be given by
injection. Scientists have
overcome this problem by
making derivatives of
penicillin G that have
modified side-chains (R in
the general penicillin
structure) that can resist
stomach acid and be given by
the oral route.