Presentation

1. MEDICAL BIOCHEMISTRY
DEPARTMENT
Organic Chemistry
(MBC 233.1)
OPURUM H. C
PHENOLS
1

2. Learning Objectives
ØUnderstanding
ØPhenols
ØMedical and Health Uses of
Phenol
ØSynthesis of Phenols
ØReactions of Phenols
2

3. Phenols
v Phenols are molecules that have a hydroxyl
group attached to the carbon atom of an
aromatic ring.
v By definition, phenol is hydroxybenzene.

4. Nomenclature
• Phenol is a common name for the compound.
• Its IUPAC name would be benzenol, derived in the same
manner as the IUPAC names for aliphatic alcohols.
• When a phenol molecule is substituted with additional
groups, either the ortho, meta, para system or the
numbering system can be employed.
• In IUPAC nomenclature, the parent molecule is called
benzenol, and substituents are always numbered with
the OH group being given the understood first position.
• For the compounds below, the first name listed is the
common name and the second is the IUPAC name.

5. Medical & Health Uses of Phenol
v Pure phenol is used in certain medical
procedures and as an ingredient in numerous
treatments and laboratory applications.
v Phenol has numerous health benefits and can
be helpful to treat a few different conditions.
v But it can be dangerous and even deadly in high
amounts.
v Be careful in places that may contain high
levels of phenol, such as industrial
facilities.
v Don’t eat or drink anything that may have
been exposed to phenol or have
uncontrolled amounts of phenol in it.

6. Phenol Injection
Ø Phenol can be injected into your muscles to treat a
condition known as muscle spasticity.
Ø This happens when your brain doesn’t communicate
properly with your spinal cord and nerves.
Ø It causes your muscles to become tight.
Ø Muscle spasticity can even interrupt your ability to walk
or talk.
Ø It can be caused by conditions like Parkinson’s
disease, cerebral palsy, or brain trauma.
Ø A phenol injection helps limit the signals sent from your
nerves to your muscles that cause contractions.
Ø This allows you to move more easily and feel less
discomfort.

7. Chemical matrixectomy
q Phenol in the form of trichloroacetic acid is
commonly used in surgeries for in-grown
toenails, especially the more severe ingrown
toenails that don’t respond to other treatments.
q A small 2001 study of 172 people found that 98.8
percent of those who received a chemical
matrixectomy with phenol cauterization had
successful results.
q However, sodium hydroxide is gradually replacing
phenol matrixectomy as an ingrown toenail
treatment because it has fewer complications
{Journal of American Podiatric Medical Association ,
2014}.

8. Vaccine preservative
q Phenol is used as a preservative in at least
four vaccines.
q It helps keep bacteria from growing in and
contaminating the vaccine solutions.
q Pneumovax 23 for conditions like
pneumonia and meningitis
q Typhim Vi for typhoid fever
q ACAM2000 for smallpox

9. Sore throat spray
q Phenol is used in some throat sprays that can help
numb your throat and relieve symptoms caused
by a sore throat, or irritation in the mouth caused
by canker sores.
q The most common brand of phenol spray is
Chloraseptic which contains about 1.4% phenol.
q Phenol spray is safe to use at the recommend dose
for a short time.
q But using too much or giving it to children younger than 3-
years old can be unsafe.
q Read the ingredients label carefully to make sure you’re not
allergic to any other components of the spray.

10. Oral analgesics
v Many phenol-based products that help relieve
pain or irritation in or around your mouth
numb tissues in the mouth and lips.
v These products are used as a short-term
treatment for the symptoms of pharyngitis.
v This happens when your throat gets inflamed
from a bacterial or viral infection.
v Phenol-based products for mouth and throat
pain are widely available and safe to use in
small doses.

11. Phenol derivatives
v Phenol-derived compounds have a variety of
uses, including:
v Chemical Peels-Phenol in trichloroacetic acid is
used to penetrate through layers of skin to get
rid of old or damaged skin.
v Food and cosmetic preservatives. Phenol
derivative butylated hydroxytoluene (BHT) is a
common FDA-approved preservative used
in cosmetics and to keep food from going bad.
v It’s safe to consume in small amounts.

12. Phenol liquid
v Phenol liquid is often used in molecular biology with
trichloro-methane and chloroform to separate RNA,
DNA, or proteins, and isolate them in the pure form.
v This process is known as liquid-liquid extraction.
v It’s done by adding an equal amount of phenol and
chloroform to a solution of cells or tissues.
v The phenol-chloroform mixture separates molecules
based on how soluble the tissue sample is in that
solution.
v The pH level of phenol helps separate the DNA and
RNA.

13. Soap and antiseptic
v Soap containing phenol-based compounds is often called carbolic
soap.
v It’s been used as an antiseptic during surgery since 1867 or more.
v It’s remembered by millions in the United Kingdom for its distinct
smell and red streaks it left on bathroom sinks.
v Carbolic soap is still widely used throughout the world especially in
countries who receive foreign aid from organizations like the
Red Cross or Doctors Without Borders.
v It provides effective, low-cost hygiene to poverty-stricken
communities.
v Over time, pure phenol has been replaced by some of its
derivatives as an antiseptic.
v One derivative is n-hexylresorcinol, which can be found in cough
drops.
v The compound, butylated hydroxytoluene (BHT), has replaced
phenol as a food antioxidant.

14. Health benefits
Antioxidants
v Plant-based compounds containing phenol are
known to be antioxidants.
v Antioxidants can stop the reaction of free
radicals with other molecules in your body,
preventing damage to your DNA as well as
long-term health effects.
v Free radicals are molecules that have lost an
electron and become unstable.
v This makes them prone to react with and damage
molecules like DNA.
v Free radicals sometimes cause the molecules they
react with to create even more free radicals.

15. Health benefits cont’d
v Antioxidant molecules are like a barrier between
free radicals and healthy molecules:
antioxidants replace the missing electron and
render it harmless.
v Some notable phenolic antioxidants with proven
health effects include:
v Bioflavonoids, found in wines, teas, fruits, and
vegetables
v tocopherols including vitamin E, found in many
fruits, nuts & vegetables
v Resveratrol, found in fruits, nuts, and red wine
v Oregano oil composed of many beneficial
phenols like carvacrol, cymene, terpinine, and
thymol.

16. Cancer prevention
v Phenol-based compounds have been found to have
some cancer prevention properties.
v A 2010 animal review in Advances in Experimental
Medicine and Biology suggested that getting phenols
from a diet heavy in plants containing phenolic
compounds and foods fortified with phenols helped
strengthen the immune system and make cells more
resistant to cancer throughout their life cycle.
v Most of this research comes from animal models, but
human studies are also promising.
v According to a 2014 paper in Current Pharmaceutical
Biotechnology, the complex structures of phenolic
compounds can help make cancer cells more
receptive to chemotherapy treatments.

17. Risks
vPhenol may have its share of uses
and health benefits, but it can also
be toxic or cause long-term health
effects if you’re exposed to it in high
amounts.

18. vHow to avoid exposure:
v Be careful at work.
v Being exposed to phenol in industrial
facilities may increase your risk of heart
disease.
v This may be partly due to exposure to many other
industrial chemicals in addition to phenol.
v Don’t eat anything that might contain phenol.
v Consuming phenol in its pure form can damage
your esophagus, stomach, intestines, and other
digestive organs.
v It can be fatal if you have enough of it at one time.

19. vHow to avoid exposure cont’d:
v Don’t put it on your skin.
v Pure phenol can damage your skin if it makes
direct contact. This can include burns and
blisters.
v Don’t inhale it.
v Laboratory animals experienced breathing
difficulties and twitching of muscles when
they breathed in a lot of phenol for even a short
period of time. Phenol has also been shown to
cause systemic organ damage in laboratory
animals.
v Don’t drink it.
v Consuming water containing a lot of phenol can
make muscles spasm and affect your ability to
walk. Too much can be fatal.

20. Synthesis of Phenols
v Phenols are prepared in large quantities by
the pyrolysis of the sodium salt of
benzene sulfonic acid, by the Dow
process, and by the air oxidation of
cumene.
v You can also prepare small amounts of
phenol by the peroxide oxidation of
phenylboronic acid and the hydrolysis of
diazonium salts.

21. Pyrolysis of sodium benzene sulfonate
v In this process, benzene sulfonic acid is
reacted with aqueous sodium hydroxide.
v The resulting salt is mixed with solid sodium
hydroxide and fused at a high temperature.
v The product of this reaction is sodium
phenoxide, which is acidified with aqueous
acid to yield phenol.

22. Dow process
In the Dow process, chlorobenzene is reacted
with dilute sodium hydroxide at 300°C and 3000
psi pressure.
The following figure illustrates the Dow process.

23. Air oxidation of cumene
v The air oxidation of cumene (isopropyl
benzene) leads to the production of both
phenol and acetone.
v The mechanisms for the formation and
degradation of cumene hydroperoxide
require closer looks, which are provided
following the figure.

24. Cumene hydroperoxide formation
q The formation of the hydroperoxide
proceeds by a free radical chain reaction.
q A radical initiator abstracts a hydrogen free
‐
radical from the molecule, creating a
tertiary free radical.
q The creation of the tertiary free radical is the
initial step in the reaction.

25. v In the next step, the free radical is attracted to
an oxygen molecule.
v This attraction produces the hydroperoxide free
radical.
v Finally, the hydroperoxide free radical abstracts a
hydrogen free radical from a second molecule of
cumene to form cumene hydroperoxide and a new
tertiary free radical.

26. Cumene hydroperoxide
degradation.
v The degradation of the cumene
hydroperoxide proceeds via a carbocation
mechanism.
v In the first step, a pair of electrons on the
oxygen of the hydroperoxide's “hydroxyl
group” is attracted to a proton of the
H 3O + molecule, forming an oxonium ion.

27. v Next, the oxonium ion becomes stabilized when the
positively charged oxygen leaves in a water
molecule.
v This loss of a water molecule produces a new
oxonium ion.
v A phenide ion shift to the oxygen atom (which creates a
tertiary carbocation) stabilizes the positively charged
oxygen.
v (A phenide ion is a phenyl group with an electron bonding
pair available to form a new bond to the ring.)

28. The carbocation is stabilized by an acid base
‐
reaction with a water molecule, leading to the
formation of an oxonium ion.
The loss of a proton stabilizes the oxonium ion.
Next, a proton is picked up by the ether oxygen in
an acid base reaction, yielding a new oxonium ion.
‐

29. v The positively charged ether oxygen pulls the electrons in the
oxygen carbon bond toward itself, thus delocalizing the
‐
charge over both of the atoms.
v The partial positive charge on the carbon attracts the
nonbonding electron pair from the oxygen of the OH group,
allowing the electrons in the original oxygen carbon bond to
‐
be released back to the more electronegative oxygen atom.
v Finally, a proton is lost from the protonated acetone
molecule, leading to the formation of acetone.