Experiment 2. Synthesis of Paracetamol

C8H9NO2

molecular formula of paracetamol

amide

functional group of paracetamol

N-(4-hydroxyphenyl)ethanamide

IUPAC name of Paracetamol

acetaminophen

trivial name of paracetamol

151.16 g/mol

molecular weight of paracetamol

odorless white crystalline solid that has a bitter taste with a pH (saturated aqueous solution) of about 6

Tylenol

Description of Paracetamol:

1. also commonly known as __________

2. most commonly taken ____________ worldwide

3. recommended as ______________ in pain conditions by the World Health Organization (WHO)

4. used for its ________________, helping to reduce fever

5. drug was initially approved by the U.S. FDA in _________

6. available in a variety of _______ including syrup form, regular tablets, effervescent tablets, injection, suppository, and other form

7. often found __________ with other drugs in more than 600 over the counter (OTC) drugs namely: allergy medications, cold medications, sleep medications, pain relievers, and other products.

1 = ?

analgesic

Description of Paracetamol:

1. also commonly known as __________

2. most commonly taken ____________ worldwide

3. recommended as ______________ in pain conditions by the World Health Organization (WHO)

4. used for its ________________, helping to reduce fever

5. drug was initially approved by the U.S. FDA in _________

6. available in a variety of _______ including syrup form, regular tablets, effervescent tablets, injection, suppository, and other form

7. often found __________ with other drugs in more than 600 over the counter (OTC) drugs namely: allergy medications, cold medications, sleep medications, pain relievers, and other products.

2 = ?

first-line therapy

Description of Paracetamol:

1. also commonly known as __________

2. most commonly taken ____________ worldwide

3. recommended as ______________ in pain conditions by the World Health Organization (WHO)

4. used for its ________________, helping to reduce fever

5. drug was initially approved by the U.S. FDA in _________

6. available in a variety of _______ including syrup form, regular tablets, effervescent tablets, injection, suppository, and other form

7. often found __________ with other drugs in more than 600 over the counter (OTC) drugs namely: allergy medications, cold medications, sleep medications, pain relievers, and other products.

3 = ?

antipyretic effects

Description of Paracetamol:

1. also commonly known as __________

2. most commonly taken ____________ worldwide

3. recommended as ______________ in pain conditions by the World Health Organization (WHO)

4. used for its ________________, helping to reduce fever

5. drug was initially approved by the U.S. FDA in _________

6. available in a variety of _______ including syrup form, regular tablets, effervescent tablets, injection, suppository, and other form

7. often found __________ with other drugs in more than 600 over the counter (OTC) drugs namely: allergy medications, cold medications, sleep medications, pain relievers, and other products.

4 = ?

1951

Description of Paracetamol:

1. also commonly known as __________

2. most commonly taken ____________ worldwide

3. recommended as ______________ in pain conditions by the World Health Organization (WHO)

4. used for its ________________, helping to reduce fever

5. drug was initially approved by the U.S. FDA in _________

6. available in a variety of _______ including syrup form, regular tablets, effervescent tablets, injection, suppository, and other form

7. often found __________ with other drugs in more than 600 over the counter (OTC) drugs namely: allergy medications, cold medications, sleep medications, pain relievers, and other products.

5 = ?

forms

Description of Paracetamol:

1. also commonly known as __________

2. most commonly taken ____________ worldwide

3. recommended as ______________ in pain conditions by the World Health Organization (WHO)

4. used for its ________________, helping to reduce fever

5. drug was initially approved by the U.S. FDA in _________

6. available in a variety of _______ including syrup form, regular tablets, effervescent tablets, injection, suppository, and other form

7. often found __________ with other drugs in more than 600 over the counter (OTC) drugs namely: allergy medications, cold medications, sleep medications, pain relievers, and other products.

6 = ?

combined

Description of Paracetamol:

1. also commonly known as __________

2. most commonly taken ____________ worldwide

3. recommended as ______________ in pain conditions by the World Health Organization (WHO)

4. used for its ________________, helping to reduce fever

5. drug was initially approved by the U.S. FDA in _________

6. available in a variety of _______ including syrup form, regular tablets, effervescent tablets, injection, suppository, and other form

7. often found __________ with other drugs in more than 600 over the counter (OTC) drugs namely: allergy medications, cold medications, sleep medications, pain relievers, and other products.

7 = ?

Nucleophilic substitution and acylation

Type of reaction involved in paracetamol synthesis

30 minutes to 2 hours

Absorption: Paracetamol is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations typically reached within ______________ after oral administration.

body, including the brain and other tissues

Distribution: Once absorbed, paracetamol is widely distributed throughout the _____________________, . It has a relatively low plasma protein binding rate, which means a significant portion of the drug is available in its free form to exert therapeutic effects.

liver

Metabolism:

1. Paracetamol is primarily metabolized in the a._________

2. It undergoes b.____________________________ to form non-toxic metabolites, which are then excreted in the urine.

3. A small fraction of the drug is metabolized by the ______________ enzyme system to form a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI).

4. Under normal conditions, NAPQI is detoxified by _________________________.

5. However, in cases of overdose, the capacity of this detoxification pathway can be overwhelmed, leading to ___________.

1 = ?

conjugation with glucuronic acid and sulfuric acid

Metabolism:

1. Paracetamol is primarily metabolized in the a._________

2. It undergoes b.____________________________ to form non-toxic metabolites, which are then excreted in the urine.

3. A small fraction of the drug is metabolized by the ______________ enzyme system to form a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI).

4. Under normal conditions, NAPQI is detoxified by _________________________.

5. However, in cases of overdose, the capacity of this detoxification pathway can be overwhelmed, leading to ___________.

2 = ?

cytochrome P450

Metabolism:

1. Paracetamol is primarily metabolized in the a._________

2. It undergoes b.____________________________ to form non-toxic metabolites, which are then excreted in the urine.

3. A small fraction of the drug is metabolized by the ______________ enzyme system to form a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI).

4. Under normal conditions, NAPQI is detoxified by _________________________.

5. However, in cases of overdose, the capacity of this detoxification pathway can be overwhelmed, leading to ___________.

3 = ?

conjugation with glutathione

Metabolism:

1. Paracetamol is primarily metabolized in the a._________

2. It undergoes b.____________________________ to form non-toxic metabolites, which are then excreted in the urine.

3. A small fraction of the drug is metabolized by the ______________ enzyme system to form a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI).

4. Under normal conditions, NAPQI is detoxified by _________________________.

5. However, in cases of overdose, the capacity of this detoxification pathway can be overwhelmed, leading to ___________.

4 = ?

hepatotoxicity

Metabolism:

1. Paracetamol is primarily metabolized in the a._________

2. It undergoes b.____________________________ to form non-toxic metabolites, which are then excreted in the urine.

3. A small fraction of the drug is metabolized by the ______________ enzyme system to form a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI).

4. Under normal conditions, NAPQI is detoxified by _________________________.

5. However, in cases of overdose, the capacity of this detoxification pathway can be overwhelmed, leading to ___________.

5 = ?

kidneys

Excretion:

a. The metabolites of paracetamol are excreted primarily via the ________.

b. The elimination half-life of paracetamol is generally _________________ in healthy individuals.

a = ?

1.5 to 3 hours

Excretion:

a. The metabolites of paracetamol are excreted primarily via the ________.

b. The elimination half-life of paracetamol is generally _________________ in healthy individuals.

b = ?

hepatotoxicity

Toxicity:

a. Overdose can lead to __________________

b. Extreme overdose can lead to _________________

a = ?

acute liver failure

Toxicity:

a. Overdose can lead to __________________

b. Extreme overdose can lead to _________________

b = ?

p-aminophenol

Procedure of Paracetamol Synthesis:

1. Suspend 2.7 grams of ___________ in 7.5 mL distilled water in a 50-mL beaker.

2. Add 3 mL of ________________.

3. Stir ________.

4. Warm on a water bath for _____________, cool.

5. Filter the solid derivative using a __________________.

6. Wash the precipitate with ____________________.

1 = ?

acetic anhydride

Procedure of Paracetamol Synthesis:

1. Suspend 2.7 grams of ___________ in 7.5 mL distilled water in a 50-mL beaker.

2. Add 3 mL of ________________.

3. Stir ________.

4. Warm on a water bath for _____________, cool.

5. Filter the solid derivative using a __________________.

6. Wash the precipitate with ____________________.

2 = ?

vigorously

Procedure of Paracetamol Synthesis:

1. Suspend 2.7 grams of ___________ in 7.5 mL distilled water in a 50-mL beaker.

2. Add 3 mL of ________________.

3. Stir ________.

4. Warm on a water bath for _____________, cool.

5. Filter the solid derivative using a __________________.

6. Wash the precipitate with ____________________.

3 = ?

10 minutes

Procedure of Paracetamol Synthesis:

1. Suspend 2.7 grams of ___________ in 7.5 mL distilled water in a 50-mL beaker.

2. Add 3 mL of ________________.

3. Stir ________.

4. Warm on a water bath for _____________, cool.

5. Filter the solid derivative using a __________________.

6. Wash the precipitate with ____________________.

4 = ?

Buchner funnel

Procedure of Paracetamol Synthesis:

1. Suspend 2.7 grams of ___________ in 7.5 mL distilled water in a 50-mL beaker.

2. Add 3 mL of ________________.

3. Stir ________.

4. Warm on a water bath for _____________, cool.

5. Filter the solid derivative using a __________________.

6. Wash the precipitate with ____________________.

5 = ?

cold water

Procedure of Paracetamol Synthesis:

1. Suspend 2.7 grams of ___________ in 7.5 mL distilled water in a 50-mL beaker.

2. Add 3 mL of ________________.

3. Stir ________.

4. Warm on a water bath for _____________, cool.

5. Filter the solid derivative using a __________________.

6. Wash the precipitate with ____________________.

6 = ?

gastrointestinal irritation

Paracetamol has minimal __________________________ compared to aspirin so it is preferred for patients who are at risk of gastrointestinal bleeding.

acetic acid

by product of paracetamol synthesis

65:30:5 mixture of hexane, ethyl acetate and acetic acid

mobile phase of TLC characterization of paracetamol

TLC

stationary phase of paracetamol synthesis

Short and Long Wave UV Light

visualization of Paracetamol in TLC

169-170 C

melting point of paracetamol

p-aminophenol (limiting material) + acetic anhydride

Reagents for Synthesis of Paracetamol