PHARMACEUTICAL MEDICINAL ORGANIC CHEMISTRY
PMOC 311 | LABORATORY | OUR LADY OF FATIMA UNIVERSITY | E. VIRTUCIO, RPH
EXERCISE 4: PREPARATION OF ACETYLSALICYLIC ACID
ACETYLSALICYLIC ACID By 1899, BAYER recognized Felix work and Bayer
ASPIRIN Aspirin was actually trademarked by the company in
Germany
The popularity of aspirin declined after the market
Acetyl releases of paracetamol (acetaminophen) in 1956
Salicylic and ibuprofen in 1969.
acid Aspirin is the oldest in a class of pharmaceuticals called
non-steroidal anti-inflammatory drugs (NSAIDs).
SYNONYMS
2-acetoxybenzoic acid
Acidum salicylicum
Aspirin
Acetylsalicylic acid is AKA Aspirin O-acetylsalicylic acid
HISTORY Polypiryna
Salicylic acid acetate
SYNTHESIS OF ASPIRIN
The structure of aspirin was derived from the
combination of an acetyl group with a known salicylic
Leaves from Willow tree were used by Egyptians as acid group. Salicylic acid is a type of Carboxylic acid with
topical poultice and is generally used for fever and may phenol. Salicylic acid, reacted with acetic
swelling. anhydride, with the introduction ACETYL GROUP. In
During the 4th century BC, the Greek doctor which the introduction of this group is called
Hippocrates, called as the father of medicine, prescribes ACETYLATION.
the leaves to be used as anti-pyretic, analgesic, and RESULTS
used to relieve pain during childbirth.
It was Edward stone, a vicar in Norton, Oxfordshire who
submitted report that details the antipyretic effect of
dried, powdered willow bark.
Salicylic acid was isolated for use as a medicine in the
19th century (1800s). However, salicylic acid is bitter
and irritates the stomach.
In 1853, French chemistry Charles Frederic Gerhardt
defined the chemical structure of salicylic acid and
synthesized acetylsalicylic acid using sodium salicylate PHYSICAL TEST
with acetyl chloride. A. Appearance: Colorless or white crystalline
B. Odor: odorless
C. Melting Point Range: 135 °C (275 °F)
CHEMICAL TEST
A. Acid Hydrolysis: Violet solution
B. Basic Hydrolysis: Clear solution
Special Notes:
ASA is colorless or characterized as white crystalline,
Unfortunately, further research regarding this was odorless and have a melting point range of 135 degrees
dropped and was picked up by German chemist Felix Celsius or 275 Fahrenheit
Hoffman, who was researching for a nonirritating pain When you subject aspirin for chemical test, following
reliever to ease his father’s rheumatism. This was in acid hydrolysis using hydrochloric acid it should turn
1897. purple. After the hydrolysis, it produces salicylic acid and
In 1897 the German chemist Felix Hoffman (working acetic acid. Upon addition of ferric chloride, the solution
under Bayer Company) synthesized the acetyl derivative turns to violet because salicylic acid contains an enol,
of salicylic acid in response to the urging of his father, specifically, a PHENOL. If you searched for the positive
who took salicylic acid for rheumatism. result for test for enols, PHENOL produces PURPLE or
Felix was able to produce a pure and stable form of ASA, VIOLET color in the presence of phenolic compounds.
and;
In basic hydrolysis, in the presence of sodium hydroxide Moderate intoxication: tachypnea, diaphoresis, ataxia,
and upon addition to acetylsalicylic acid, it produces and anxiety
SODIUM ACETYLSALICYLATE and WATER that will Severe intoxication: abnormal mental status, seizures,
show a clear solution. acute lung injury, and renal failure
USES
Analgesic for the treatment of mild to moderate pain
o 325 – 650 mg (adult dosage)
Anti-inflammatory agent for the treatment of soft tissue
and joint inflammation
o 45 mg/kg (adult dosage)
Antipyretic drug
o 325 – 650 mg (adult dosage)
Antiplatelet/antithrombosis
o 40 – 80 mg
CONTRAINDICATIONS
Active peptic ulcer
Hemostatic disorders (including anticoagulant and
thrombolytic treatment)
Hypersensitivity
Asthma Aspirin have dose-dependent effect based on the
Kidney disease (may exacerbate the condition) plasma salicylate concentration.
Hyperuricemia or gout (because ASA inhibits the
kidney’s ability to excrete uric acid) TOXICOLOGY – ACUTE TOXICITY
Hemolytic anemia (G6PD deficient)
Dengue fever (increased bleeding tendency)
Children or adolescents with viral infections
Reye’s syndrome
Special Notes:
Aspirin is known to inhibit COX-1 activity, and COX-1
can be found on the normal lining of the stomach and
intestine allowing it to protect the organ from different
digestive juices. If a patient has a peptic ulcer, knowing
that aspirin is a COX inhibitor, it would exacerbate
ulcerations of the stomach.
It may also cause increased bleeding
Reye’s syndrome is due to the damage caused by
salicylates to cellular mitochondria. This causes
complications or clinical manifestations related to
mitochondrial oxidation and metabolic disorders of Fatty
Acid transport.
TOXICOLOGY
Acute ingestion of <150 mg/kg will produce mild
intoxication;
Acute ingestion of 150-300mg/kg will produce moderate
intoxication; and
Acute ingestion of >300 mg/kg is likely to produce
severe intoxication
Chronic intoxication may occur with ingestion of more
than 100 mg/kg/d for 2 or more days
Special Notes:
Mild intoxication is manifested for acute ingestion of less According to Tintinalli’s Emergency Medicine there
than 150 milligrams per kg dose are several manifestation of aspirin toxicity depending
Moderate intoxication, that is 150-300mg per kilogram; on the dose ingested
and Mixed respiratory alkalemia, metabolic acidosis, coma,
Severe intoxication, that is greater than 300mg/kg. hypoglycemia, hyperthermia, and pulmonary edema
Mild intoxication: end-organ toxicity is usually (severe intoxication), death caused by CNS failure and
manifested by tinnitus, dizziness, nausea and vomiting cardiovascular collapse
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TOXICOLOGY – TREATMENT
Toxicity is managed with a number of potential
treatments:
o activated charcoal,
o sodium bicarbonate, and
o dialysis.
Intoxication may cause increased metabolic activity
particularly it may cause metabolic acidosis. Therefore,
sodium bicarbonate may help correct metabolic
acidosis. Furthermore, dextrose can be given if
hypoglycemia occurs. Other clinical manifestations
should also be treated with appropriate medications. For
example, in case of seizure, we could give BZD. But,
generally, the main goal is to treat the most urgent
complication.
REVIEW QUESTIONS
Question: Why is aspirin, a synthetic compound, a more
satisfactory pain-reliever than salicylic acid, a natural
compound?
Answer: ASA, a synthetic compound, is a more satisfactory
pain-reliever than salicylic acid because it is less
irritating to the stomach and not bitter.
Question: Why do people who do not have headaches and
pain regularly take small doses of aspirin?
Answer: People who do not have H/A and pain regularly
take small doses of ASA because it is used as a
secondary prevention of strokes and heart attacks by
completely blocking the TXA2 production and its ability
to induce aggregation.
Question: Discuss the metabolic changes that take place in
aspirin. How can it cause methemoglobinemia?
Answer: ASA could cause methemoglobinemia because
ferrous form in the blood is turned into the ferric form.
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