INVESTIGATORY PROJECT ON

ASPIRIN
Synthesis & Application

Abstract
[In this investigatory project, I have discussed many important points like synthesis, usage along with
side effects due to high dose, chemical structure of aspirin and its aspirin.]

Ishana Khan
210063@ntskolkata.org
 Contents
Acknowledgement ....................................................................................................................................... 3
Introduction ................................................................................................................................................ 4
Discovery ..................................................................................................................................................... 5
Physical properties ..................................................................................................................................... 6
Production ................................................................................................................................................... 6
i. Abstract .................................................................................................................................................... 6
ii. Safety Considerations: ........................................................................................................................... 8
iii. Procedure ............................................................................................................................................... 8
iv. Report ..................................................................................................................................................... 9
Mechanism of action of aspirin ............................................................................................................... 11
Application ................................................................................................................................................ 11
Warnings & Precautions .......................................................................................................................... 12
i. Before taking this medicine................................................................................................................... 12
ii. How should aspirin be taken? ............................................................................................................. 13
iii. What happens if a dose is missed? ..................................................................................................... 13
iv. What happens if it is overdosed? ........................................................................................................ 14
v. Procedure to avoid ............................................................................................................................... 14
vi. Aspirin side effects ............................................................................................................................... 14
vii. What is the effects of other drugs on aspirin? ................................................................................. 15
Research .................................................................................................................................................... 16
Psychiatry .................................................................................................................................................. 16
Bipolar disorder ........................................................................................................................................ 16
Infectious diseases ..................................................................................................................................... 16
Cancer prevention .................................................................................................................................... 16
Conclusion ................................................................................................................................................. 17
Bibliography .............................................................................................................................................. 17
 Acknowledgement
I would like to thank my teacher Subrata sir who gave me
this opportunity to work on this project. I got to learn a lot
from this project about preparation and benefits of aspirin.
I would also like to thank our school principal, Mrs Satabdi
Bhattacharjee.
I would also like to extend my heartfelt thanks to your
parents because without their help this project would not
have been successful. Finally, I would like to thank my dear
friends who have been with me all the time.
— Ishana
 Introduction
What is aspirin?

Aspirin, also known as acetylsalicylic acid, is a medication used to reduce

pain, fever, or inflammation.

IUPAC ID:
2-Acetoxybenzoic acid

Formula: C₉H₈O₄

Molar mass: 180.158 g/mol

Metabolism: Liver (CYP2C19 and possibly CYP3A), some is also

hydrolysed to salicylatein the gut wall.

Protein binding: 80–90%

Elimination half-life: Dose-dependent; 2–3 h for low doses (100 mg or

less), 15–30 h for large doses.

AHFS/Drugs.com: Monograph
 Discovery

In 1897, Felix Hoffman, a German chemist working for the Bayer

company, was able to modify salicylic acid to create acetylsalicylic acid,
which was named aspirin (Fig. 1). The following year, Heinrich Dreser
at Bayer dismissed the market potential of aspirin on the ground that it
had an “enfeebling” action on the heart (“The product has no value”).
His real reason for ignoring aspirin was his preoccupation with the sales
potential of another new drug—heroin (first synthesized in the Bayer
laboratory in 1897)—which Bayer was about to launch as a cough
remedy.6 Arthur Eichengruen (whose job it was to originate new
products at Bayer) refused to accept Dreser's rejection of acetylsalicylic
acid and continued to press for its development.6 Eventually, Dreser
reneged and tested aspirin on himself and on his rabbits, confirming its
therapeutic properties. Subsequently, aspirin was found to be more
tolerable to the stomach than salicylic acid.7 Felix Hoffmann's
innovation led to the widespread modern use of aspirin for pain relief.
His acetylation of salicylic acid also proved fortunate in another way,
because the modification is important to aspirin's ability to prevent
cardiovascular events.
Fig. 1 Acetylsalicylic acid (aspirin) retains the carboxyl group (COOH) of salicylic acid and
makes a substitution in the hydroxyl group (OH). The drug was developed at Bayer by Felix
Hoffmann. Acetylation made aspirin more tolerable to the gastrointestinal tract, which led to
widespread use.

Physical properties
Aspirin, an acetyl derivative of salicylic acid, is a white,
crystalline, weakly acidic substance, with a melting point of 136
°C (277 °F), and a boiling point of 140 °C (284 °F) Its acid
dissociation constant (pKa) is 3.5 at 25 °C (77 °F).
Production
i. Abstract
In this experiment you will synthesize aspirin and determine the yield or
fraction of the theoretical amount which can be made. The purity of the
product is confirmed by measuring its melting point range.
Aspirin is the common name for the compound acetylsalicylic acid,
widely used as a fever reducer and as a pain killer. Salicylic acid, whose
name comes from Salix, the willow family of plants, was derived from
willow bark extracts. In folk medicine, willow bark teas were used as
headache remedies and other tonics. Nowadays, salicylic acid is
administered in the form of aspirin which is less irritating to the stomach
than salicylic acid.
To prepare aspirin, salicylic acid is reacted with an excess of acetic
anhydride. A small amount of strong acid is used as a catalyst which
speeds up the reaction. In this experiment, phosphoric acid will be used as
the catalyst. The excess acetic acid will be quenched with the addition of
water. The aspirin product is not very soluble in water so the aspirin
product will precipitate when water is added. The synthesis reaction of
aspirin is shown below:

Since acetic acid is very soluble in water, it is easily separated from the
aspirin product. The aspirin isolated in this step is the “crude product”. A
“purified product” can be obtained through recrystallization of the crude
product in hot ethanol. In this experiment, the crude product will be the
desired product. The percent yield of the crude product will be determined
for this reaction. The purity of the product will also be analyzed. The
product will be analyzed by three different methods: melting point,
titration, and spectroscopic assay. The melting point range of pure aspirin
is 138-140 C and the melting point range of the salicylic acid starting
material is 158-161 C. If impurities are present in your crude sample,
the melting point range for your product will be lower than the range of
pure aspirin. Also, your melting point range may be greater than 2 degrees.
From the titration of your sample, the moles of acetylsalicylic acid present
can be determined assuming that there is not a large percentage of an acid
impurity present in your crude sample.
The spectroscopic analysis of aspirin will involve the complexing of
iron(III) to the deprotonated form of salicylic acid (salicylate ion) to give
a purple solution. Only the salicylate ion complexes to iron(III). Your
aspirin product as well as a commercial aspirin tablet will be compared to
a standard 0.15% ferricsalicylate solution. In the presence of moisture,
aspirin may decompose (hydrolysis) into salicylic acid and acetic acid.
This reaction is the reverse of the synthesis reaction. The maximum
allowable amount of free salicylic acid in an aspirin sample is 0.15%
salicylic acid.
ii. Safety Considerations:
This experiment uses salicylic acid, acetic anhydride and phosphoric
acid. The salicylic acid and aspirin may cause irritation to your skin or
eyes, but are basically not hazardous. An excess of these can be disposed
of in the sink or if packaged, in the trash. If you spill some, wipe it up
with a wet paper towel and throw the towel in the trash. The acetic
anhydride and phosphoric acid can cause bad burns. Use them in the
hood. Be sure to wear gloves and safety goggles when using these
chemicals. Excess chemicals must be disposed of in the plastic tub of
water. This will convert the acetic anhydride to vinegar and dilute the
phosphoric acid. If you spill a lot of either of these, notify your
instructor

iii. Procedure
1. Weigh out 3.0 g of salicylic acid and place in a 250 ml Erlenmeyer
flask.
2. Measure out 6.0 ml of acetic anhydride and add this to your flask. Be
sure to do this in the hood and wear your goggles.
Don't let the acetic anhydride contact your skin and don't get the vapors in
your eyes.
3. Carefully add 5 to 10 drops of 85% phosphoric acid, a catalyst, to the
flask and swirl to mix everything thoroughly.
4. Still in the hood, heat the mixture for about 10 min. in a beaker of warm
water (70-80 oC).
5. After heating, cautiously add 20 drops of distilled water.
6. Next add 20 ml of distilled water and cool in an ice bath. You can do
this at your bench. If crystals do not appear, you can scratch the walls
of the flask with a stirring rod to induce crystallization.
7. Filter the solid aspirin through a piece of pre-weighed filter paper using
a Buchner funnel and the aspirator. Wash the crystals with 2-3 ml of
chilled water. The liquid is mostly water and can be washed down the
 sink. Allow the air to be drawn through the solid and filter paper for 15
minutes. Be sure to record the filter paper weight in your notebook.

8. Place the filter paper with the product in a watch glass and put it in the
oven at 100 oC for about 30 min. until dry.
9. Put the dry aspirin and the filter paper into a pre-weighed plastic bag
and weigh again.
10. Measure the melting point range with the Meltemp Apparatus (your
instructor will demonstrate) and compare to the value for pure aspirin
of 138-140 oC.
11. Calculate the weight of your product by subtracting the weight of the
paper and bag from the total. The theoretical (maximum) yield is 3.9
grams. What percent of this did you get? This is your percent yield.
Record it in your notebook and turn in your product to the Stockroom.

iv. Report
Report the theoretical yield and the percent yield of the aspirin product.
Compare the melting point of you aspirin product to the theoretical
melting point (138-140 C). Is the crude product above of below this
mark?Explain why this is the case.
Determine the moles of aspirin from the titration and calculate the percent
purity of the crude aspirin product from the titration analysis.
Plot a Beer’s Law graph of the standard 0.15% salicylic acid solution (C)
on excel with Absorbance (yaxis) vs % salicylic acid (x-axis). To make a
Beer’s Law plot, enter % Salicylic Acid into one column on the excel
spread sheet (0 and 0.15) and absorbance into the next column (0 and the
absorbance 5 reading).

Highlight the data and select insert, and scatter (w/ only markers). Right
click a data point and select add trend line. Now set the y-intercept to 0
and check the display equation box. To add titles to the plot, select layout,
axis titles, and then chart titles.
The % concentration for samples A and B can be determined by plugging
in the absorbance readings for those samples into the linear equation and
solving for x. Clearly state if the samples are below the maximum
allowable limit for percent salicylic acid (0.15 %).

Mechanism of action of aspirin

Trimolecular structure of Aspirin

Aspirin causes several different effects in the body, mainly the reduction
of inflammation, analgesia (relief of pain), the prevention of clotting,
and the reduction of fever. Much of this is believed to be due to
decreased production of prostaglandins and TXA2. Aspirin's ability to
suppress the production of prostaglandins and thromboxanes is due to its
irreversible inactivation of the cyclooxygenase (COX) enzyme.
Cyclooxygenase is required for prostaglandin and thromboxane
synthesis. Aspirin acts as an acetylatingagent where an acetyl group is
covalently attached to a serine residue in the active site of the COX
enzyme.[1] This makes aspirin different from other NSAIDs (such as
diclofenac and ibuprofen), which are reversible inhibitors. However,
other effects of aspirin, such as uncoupling oxidative phosphorylation in
mitochondria, and the modulation of signaling through NF-κB, are also
being investigated. Some of its effects are like those of salicylic acid,
which is not an acetylating agent.

Application
Aspirin is a salicylate (sa-LIS-il-ate). It works by reducing substances in
the body that cause pain, fever, and inflammation.

Aspirin is used to treat pain, and reduce fever or inflammation. It is

sometimes used to treat or prevent heart attacks, strokes, and chest pain
(angina).
Aspirin should be used for cardiovascular conditions only under the
supervision of a doctor.

Warnings & Precautions

You should not use aspirin if you have a bleeding disorder such as
hemophilia, a recent history of stomach or intestinal bleeding, or if you
are allergic to an NSAID (non-steroidal anti-inflammatory drug) such as
Advil, Motrin, Aleve, Orudis, Indocin, Lodine, Voltaren, Toradol,
Mobic, Relafen, Feldene, and others.

Do not give this medication to a child or teenager with a fever, flu

symptoms, or chickenpox. Salicylates can cause Reye's syndrome, a
serious and sometimes fatal condition in children.

i. Before taking this medicine

Do not give this medicine to a child or teenager with a fever, flu
symptoms, or chickenpox. Aspirin can cause Reye's syndrome, a
serious and sometimes fatal condition in children.

You should not use aspirin if you are allergic to it, or if you have:

• a recent history of stomach or intestinal bleeding;

• a bleeding disorder such as hemophilia; or
• if you have ever had an asthma attack or severe allergic reaction
after taking aspirin or an NSAID (non-steroidal anti-inflammatory
drug) such as Advil, Motrin, Aleve, Orudis, Indocin, Lodine,
Voltaren, Toradol, Mobic, Relafen, Feldene, and others.
To make sure this medicine is safe for you, tell your doctor if you have:

• asthma or seasonal allergies;

• stomach ulcers;
• liver disease;
• kidney disease;
• a bleeding or blood clotting disorder;
• gout; or
 • heart disease, high blood pressure, or congestive heart failure.
Taking aspirin during late pregnancy may cause bleeding in the
mother or the baby during delivery. Tell your doctor if you are
pregnant or plan to become pregnant.

Aspirin can pass into breast milk and may harm a nursing baby. You
should not breastfeed while using this medicine.

ii. How should aspirin be taken?

Take aspirin exactly as directed on the label, or as prescribed by your
doctor. Do not use in larger or smaller amounts or for longer than
recommended.

Always follow directions on the medicine label about giving aspirin to a

child.

Take with food if aspirin upsets your stomach.

You must chew the chewable tablet before you swallow it.

Do not crush, chew, break, or open an entericcoated or

delayed/extended-release pill. Swallow the pill whole.

If you need surgery, tell the surgeon ahead of time that you are using this
medicine. You may need to stop using it for a short time.

Do not use aspirin if you smell a strong vinegar odor in the bottle. The
medicine may no longer be effective.

Store at room temperature away from moisture and heat.

iii. What happens if a dose is missed?

Since aspirin is used when needed, you may not be on a dosing schedule.
If you are on a schedule, use the missed dose as soon as you remember.
Skip the missed dose if it is almost time for your next scheduled dose.
Do not use extra medicine to make up the missed dose.

iv. What happens if it is overdosed?

Seek emergency medical attention or call the Poison Help line at 1-
800222-1222.

Overdose symptoms may include stomach pain, vomiting, diarrhea,

vision or hearing problems, fast or slow breathing, or confusion.

v. Procedure to avoid
Avoid drinking alcohol while you are taking aspirin. Heavy drinking can
increase your risk of stomach bleeding.

If you are taking this medicine to prevent heart attack or stroke, avoid
also taking ibuprofen (Advil, Motrin). Ibuprofen may make this
medicine less effective in protecting your heart and blood vessels. If you
must use both medications, ask your doctor how far apart your doses
should be.

Ask a doctor or pharmacist before using any cold, allergy, or pain

medication. Many medicines available over the counter contain aspirin
or an NSAID. Taking certain products together can cause you to get too
much of this type of medication. Check the label to see if a medicine
contains aspirin, ibuprofen, ketoprofen, naproxen, or an NSAID.
vi. Aspirin side effects
Get emergency medical help if you have signs of an allergic reaction to
aspirin: hives; difficult breathing; swelling of your face, lips, tongue, or
throat.

Stop using this medicine and call your doctor at once if you have:
 • ringing in your ears, confusion, hallucinations, rapid breathing,
seizure (convulsions);
• severe nausea, vomiting, or stomach pain;
• bloody or tarry stools, coughing up blood or vomit that looks like
coffee grounds;
• fever lasting longer than 3 days; or
• swelling, or pain lasting longer than 10 days.
Common aspirin side effects may include:

• upset stomach, heartburn;

• drowsiness; or
• mild headache.

vii. What is the effects of other drugs on aspirin?

Ask your doctor before using aspirin if you take an antidepressant such
as citalopram, escitalopram, fluoxetine (Prozac), fluvoxamine,
paroxetine, sertraline (Zoloft), trazodone, or vilazodone. Taking any of
these medicines with an NSAID may cause you to bruise or bleed easily.

Ask a doctor or pharmacist if it is safe for you to use this medicine if you
are also using any of the following drugs:

• a blood thinner (warfarin, Coumadin, Jantoven), or other

medication used to prevent blood clots; or
• other salicylates such as Nuprin Backache Caplet, Kaopectate,
KneeRelief, Pamprin Cramp Formula, Pepto-Bismol, Tricosal,
Trilisate, and others.
This list is not complete. Other drugs may interact with aspirin,
including prescription and over-the-counter medicines, vitamins, and
herbal products. Not all possible interactions are listed in this medication
guide.
 Research
Psychiatry
In psychiatric research, aspirin has been investigated as an add-on
treatment for different disorders in the context of drug
repurposing strategies, considering the role of inflammation in the
pathogenesis of severe mental illnesses.
Bipolar disorder
Aspirin has been repurposed as an add-on treatment for depressive
episodes in subjects with bipolar disorder. However, meta-analytic
evidence is based on very few studies and does not suggest any
efficacy of aspirin in the treatment of bipolar depression. Thus,
notwithstanding the biological rationale, the clinical perspectives of
aspirin and antiinflammatory agents in the treatment of bipolar
depression remain uncertain.
Infectious diseases
Several studies investigated the anti-infective properties of aspirin for
bacterial, viral and parasitic infections. Aspirin was demonstrated to
limit platelet activation induced by Staphylococcus aureus and
Enterococcus faecalis and to reduce streptococcal adhesion to heart
valves. In patients with tuberculous meningitis, the addition of aspirin
reduced the risk of new cerebral infarction [RR = 0.52 (0.290.92)]. A
role of aspirin on bacterial and fungal biofilm is also being supported
by growing evidence.

Cancer prevention
Aspirin might weakly reduce the risk of breast cancer per a 2020
metaanalysis.
 Conclusion
Aspirin, the original wonder drug, has long been a go-to medicine for
millions, a Jack-of-all trades remedy that is readily available and cheap.
Championed for its ability to relieve pain, fever and inflammation, aspirin
has been a staple in home medicine cabinets and first-aid kits for more
than a century.

Yet in recent years its reputation has been sullied by recognition of

potentially serious side effects, especially dangerous bleeding in the
gastrointestinal tract or the brain. Given aspirin’s longevity and over-
thecounter status, those risks are sometimes overlooked by consumers
who take it with less care than is medically warranted.

Widespread reports that aspirin can help prevent heart attacks, strokes and
colorectal cancer have prompted many people to swallow either a regular
or low-dose (baby) aspirin every day without first consulting their doctors
or taking their susceptibility to complications into account. People who
rely solely on aspirin’s preventive abilities or advice from friends and
family may use it inappropriately, tipping the balance more toward risks
than benefits.

Whether aspirin might be a miracle or a menace for you depends largely

on knowing where you fit on the spectrum of its known benefits and risks.
There is one important exception: If you think you are having a heart
attack, immediately after calling 9-1-1, chew a regular 325-milligram
aspirin or four low-dose ones in hopes of limiting the heart-damaging
effects of a clot.

Bibliography
1. www.teachersfirst.com/lessons/forensics/ink-lab.html
2. www.reachoutmichigan.org/funexperiments/quick/csustan/mrsketch.htm
3. https://en.wikipedia.org/wiki/Mechanism_of_action_of_aspirin
4. https://en.wikipedia.org/wiki/Aspirin
5. https://www.drugs.com/aspirin.html
6. https://www.nytimes.com/2020/03/09/well/live/aspirin-the-original-
wonderdrug.html
7. https://g.co/kgs/a2Mtj7
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894700/