UNIVERSIDAD DE ZAMBOANGA

School of Allied Medicine (SAM)

Pharmacy Department
PHARM CHEM – 2 LABORATORY

Name: Jasher Dave C. Acabal Course/Sec: BSPh- 3B Date Submitted: April 5, 2018
Group Name: Schedule: TThS (6:00-8:00 pm) Date Performed: April 5, 2018

Exercise No. 4 – SYNTHESIS OF ACETYLSALICYLIC ACID

I. OBJECTIVE:
To synthesize Acetylsalicylic acid from Salicylic acid and Acetic anhydride

II. MATERIALS:
Reagents: Apparatus:
Salicylic acid Glass Tubing
Acetic anhydride Bunsen Burner
Phosphoric acid, 85% Water Bath
Activated Charcoal Erlenmeyer Flask
Ferric Chloride, T.S. Beaker
Sodium hydroxide, 1N Funnel
Concentrated Sulfuric acid Tripod
Sulfuric acid, 2N Filter Paper
Ethanol Watch Glass

III. PROCEDURE:

1. Weigh 3.0 g of Salicylic acid and place it in a 250mL Erlenmeyer Flask.

2. Measure 6.0mL of Acetic anhydride and add it to the Flask. (Note: Do this inside the hood and wear
goggles).
3. Add carefully 5 to 10 drops of 85% Phosphoric acid to the flask and swirl to mix thoroughly.
4. Heat the mixture for about 10 minutes in a beaker of warm water (78-80⁰C).
5. Add cautiously 20 drops of distilled water.
6. Add another 20mL of water and cool in an Ice Bath. Scratch the Walls of the Flask with Stirring Rod to
induce Crystallization.
7. Filter the Solid Aspirin through a piece of pre-weighed Filter Paper using a Funnel.
8. Wash the Crystals with 2-3mL Chilled Water.
9. Place the Filter with the Product on a Watch Glass and Put it in the Oven @ 100⁰C for about minutes
until Dry.
10. Weigh the Aspirin.
11. Compute for the % yield.

IV. Chemical Reactions Involved

Enumerate All Observed Reactions:

1. Salicylic Acid is o-hydoxy benzoic acid. This compound has both a phenol functional group and a
carboxylic acid.

2. Acetic anhydride is an anhydride. Aspirin is a carboxylic acid and an ester. Acetic acid is a carboxylic
acid. Phosphoric acid is added as a catalyst.

3. after the reaction is complete, water is added

V. DATA:

V.

Actual Yield: No Answer The reasons are due to lack of time and
Theoretical Yield: No Answer
availability of reagents itself.
Percentage Yield: No Answer

VI. COMPUTATIONS:

(Molecular Weight of the Product) (Weight of the Reactants)

THEORETICAL YIELD = _____________________________________________________________

Molecular Weight of the Reactants

Actual Yield
PERCENTAGE YIELD = ________________________ x 100

Theoretical Yield

VII. IDENTIFICATION TESTS:

A. Physical Tests:

. 1.Color: Yellowish 4. Melting Point: . 138–140 ° C.

2. Odor: Punget vinegar 5. Boiling Point : 158-161 °C
3. Appearance: Crystals

B. Chemical Tests:
1. Reaction with Ferric chloride:
Heat a Small Amount of Aspirin with Water for Several Minutes. Cool and add 1 or 2
Drops of Ferric Chloride T.S

Result: Yellow to Brown

Reaction Involved: 3 C7H6O3 (aq) + FeCl3 (aq) ------> Fe(C7H5O3)3 (aq) + 3 HCl (aq)

2. Boil about 0.5g of Aspirin with 10mL of 1 N Sodium hydroxide. Cool and Add 10mL of 2N
Sulfuric acid.

Result: Violet color

Reaction Involved: CH3COOC6H4COOH(s) + 2NaOH(aq) CH3COONa(aq)+ HOC6H4COONa(aq)+

H2O(l).
 3. Filter the Mixture obtained in Procedure 2; add to the Filtrate 3mL of ethanol and 3mL of
Sulfuric acid; and warm.

Result: Orange-red color

Reaction Involved: No Reaction

VIII. CONCLUSION:

I therefore conclude that in Part 1, the purpose of the lab is to prepare acetylsalicylic acid, commonly called
aspirin, and determine the experiment yield of a synthesis of Aspirin. Aspirin is synthesized in a laboratory. Its
synthesis is classified as an esterification reaction. Making aspirin is an extremely important experiment, not
only for the people who have headaches and pains, but also for a chemistry student. Of course, it is important
to know about the one medication that has been used for thousands of years from things like neck pains to
influenza. Though aspirin is not able to cure any of these ailments, it helps make them more bearable and
allows people to do what they want to do: to live life without worrying about being in pain or feeling sick. If
everyone can do this experiment, it might even be useful for people who want to make their own brand of
aspirin in the future, creating businesses and companies, which result in jobs and a better economy. People
can improve on the aspirin we have today, and who knows, someone might invent aspirin that has no side-
effects. It is an almost impossible chance, but anything can happen. In my point of view, making ASA helps
any chemistry student (like myself) because it shows us the practical side of chemical reactions, and how one
substance can result from putting two substances together. Not only does it show us the ‘fun’ mixing side of
chemistry, but it also helps us to practise the calculations, which are equally important

Revised & Modified: 112016 benxvirgo, RPh

IX. QUESTIONS: Answer Substantially:

1. Give the Product of Aspirin hydrolysis, & the Balanced Chemical Reaction Involved.

To prepare aspirin, salicylic acid is reacted with an excess of acetic anhydride. A small amount of a 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 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 % yield of the crude product will be determined
for this reaction. The purity of the product will also be analysed. The product will be analysed by three different
methods: melting point, titration, and spectroscopic assay.

2. Why the Salt form is used, in place of the Original Acetylsalicylic acid in dosage form formulation?

The sodium salt (Sodium salicylate), a shiny white powder, is used for antiseptics preparations and as a
preservative. In addition to its analgesic and antipyretic properties, salicylic acid possesses keratinolytic
properties and fungicidal properties. It ans its derivatives are used in the treatment of hyperkeratotic, dandruff,
ichthyosis and psoriasis as well as in the treatment of fungal skin infections such as tinea. Para-Aminosalicylic
acid (abbreviated PAS and PASA) is an analogue of para-aminobenzoic acid (abbreviated PABA) that inhibits
folic acid synthesis in Mycobacterium tuberculosis and is bacteriostatic, inhibits growth and multiplication of
the tubercle bacillus. Para-Aminosalicylic acid and its sodium salt (sodium p-Aminosalicylate) are
bacteriostatic against mycobacteria and used in the treatment of tuberculosis; administered orally. Brand
names are Tubasal, Nemasol Sodium and etc. Aminosalicylic acids are pharmaceutically active ingredients
including anti-infectives against colds, flu, or other virus infections. Mesalamine (5-aminosalicylic acid,
abbreviated 5-ASA) an active metabolite of sulfasalazine, used to treat inflammation of the rectum and lower
colon, mild to moderate ulcerative colitis proctosigmoiditis, and proctitis. Para-Aminosalicylic acid (4-
hydroxybenzoic acid) is used as an intermediate of bacteriostatic agent specially for parabens (alkyl esters of
p-hydroxy benzoic acid) which used in food and personal care products as a preservative. It is applied in the
production of liquid crystal polymers. It is also used as an intermediate of dyes, insecticides, pharmaceutical,
pesticides and other chemical compounds. Salicylic Acid and its derivatives are important for the preparation
of other pharmaceutical products, dyes, flavours, and preservatives.

3. Give the Different Therapeutic Uses of Acetylsalicylic acid, & explain the Mechanism of Action of
each.

The therapy of rheumatism began thousands of years ago with the use of decoctions or extracts of herbs or
plants such as willow bark or leaves, most of which turned out to contain salicylates. Following the advent of
synthetic salicylate, Felix Hoffman, working at the Bayer company in Germany, made the acetylated form of
salicylic acid in 1897. This drug was named "Aspirin" and became the most widely used medicine of all time.
In 1971, Vane discovered the mechanism by which aspirin exerts its anti-inflammatory, analgesic and
antipyretic actions. He proved that aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) inhibit the
activity of the enzyme now called cyclooxygenase (COX) which leads to the formation of prostaglandins (PGs)
that cause inflammation, swelling, pain and fever. However, by inhibiting this key enzyme in PG synthesis, the
aspirin-like drugs also prevented the production of physiologically important PGs which protect the stomach
mucosa from damage by hydrochloric acid, maintain kidney function and aggregate platelets when required.
This conclusion provided a unifying explanation for the therapeutic actions and shared side effects of the
aspirin-like drugs. Twenty years later, with the discovery of a second COX gene, it became clear that there are
two isoforms of the COX enzyme. The constitutive isoform, COX-1, supports the beneficial homeostatic
functions, whereas the inducible isoform, COX-2, becomes upregulated by inflammatory mediators and its
products cause many of the symptoms of inflammatory diseases such as rheumatoid and osteoarthritis.
4. What are the Side Effects of Acetylsalicylic acid? Enumerate as Many & Explain.

 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.

5. What are the conditions that Lead to Gastric Mucosal Irritation of Acetylsalicylic acid?

The gastric irritant effects of aspirin were studied in rats treated with a variety of physical and “disease”
(inflammatory) stress conditions (which may mimic responses to some stress states encountered clinically
with the object of establishing whether these stress states increase the susceptibility of the gastric mucosa to
the potentially ulcerogenic actions of aspirin. While exposure to physical (eg, cold) stress conditions markedly
increased the sensitivity of the gastric mucosa to aspirin, exposure to various disease stressors (eg, adjuvant
arthritis, acute pain, or paw inflammation) did not appreciably affect the mucosal sensitivity to this drug.
Attempts were made to determine the mechanisms of the physical stress plus aspirin interaction by use of
pharmacological agents. The results suggest a major involvement of the parasympathetic-vagal, sympathetic,
and histamineproducing systems, but not the adrenocortical axis, in this model of gastric ulcerogenesis. No
differences were observed in the mucosal uptake of aspirin, showing that accelerated uptake of the drug is not
a factor in the development of gastric ulceration.

6. What is the Storage Requirement for Acetylsalicylic acid?

Stable. Keep dry. Incompatible with strong oxidizing agents, strong bases, strong acids, various other
compounds such as iodides, iron salts, quinine salts, etc.

Revised & Modified: 112016 benxvirgo, RPh

References

Reading Materials

Acetylsalicylic Acid 2nd Edition-p-97 by Karsten Schrör

Mordant Chemical Book 5th Edition Chemistry Book
Remington: The Science and Practice of Pharmacy edited by David B. Troy, Paul Beringer

Web sources

http://msds.chem.ox.ac.uk/AC/acetylsalicylic_acid.html
https://www.google.com.ph/=What+is+the+Storage+Requirement+for+Acetylsalicylic+acid%3F&oq=
What+is+the+Storage+Requirement+for+Acetylsalicylic+acid%3F&gs_l=
https://onlinelibrary.wiley.com/doi/full/10.1002/047084289X.rn01873
https://www.google.com.ph/ =synthesis+of+aspirin+references