SYNTHESIS OF ACETAMINOPHEN

DESCRIPTIONAcetaminophen (Paracetamol)

- Is an odorless, slightly bitter taste white crystalline powder.- It is soluble in organic solvents such as methanol and ethanol but slightly soluble in water and ether. Its pH range is 5.5 - 6.5 based on saturated aqueous solution. It is chemically known as N- Acetyl-P-Aminophenol (APAP), which was derived from the interaction of p-aminophenol and an aqueous solution of acetic anhydride.

Acetaminophen is a nonprescription analgesic and antipyretic drug similar to aspirin. Acetaminophen is classified as a mild analgesic. It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies. In combination with opioid analgesics, acetaminophen can also be used in the management of more severe pain such as post-surgical pain and providing palliative care in advanced cancer patients. Though acetaminophen is used to treat inflammatory pain, it is not generally classified as an NSAID because it exhibits only weak anti-inflammatory activity.

USES OF REAGENTS

P-aminophenol

SYNONYMS 4-Aminophenol, para-aminophenol

PREPARATION: It is produced from phenol by nitration followed by reduction with iron. Alternatively, the partial hydrogenation of nitrobenzene affords phenylhydroxylamine, which rearranges primarily to 4-aminophenol:

C6H5NO2 + 2 H2 → C6H5NHOH + H2OC6H5NHOH → HOC6H4NH2

USES: Use as the limiting reactantP-Aminophenol is a building block

compound. Prominently, it is the final intermediate in the industrial synthesis of paracetamol. Treating p-aminophenol with acetic anhydride gives paracetamol.

 Other uses: p-Aminophenol is used in production of

sulfur and azo dyes;p-Aminophenol and it derivatives (metol,

glycine and amidol) are photo developers;

rubber antioxidant

Acetic AnhydrideSYNONYMS: ethanoic anhydride, Acetic

oxide, Acetyl oxideFORMULA: (CH3CO)2O (commonly abbrev,

Ac2O)Acetic Anhydride is a clear, colorless liquid

with a very pungent, penetrating, vinegar-like odor that combines with water to form acetic acid. It is soluble in ether, chloroform and benzene. It reacts with alcohols Acetic anhydride is prepared commercially in either of two ways. : Acetaldehyde is converted into acetic anhydride by atmospheric oxidizing the liquid acetaldehyde in the presence of a metal acetate as the catalyst (Oxidation process).

USES: Use in the acetylation of p- aminophenol to yield Acetaminophen.

Other uses: Its largest application is for the

conversion of cellulose to cellulose acetate, which is a component of photographic film and other coated materials.

It is also used as a wood preservative via autoclave impregnation to make a longer lasting timber.

In starch industry, acetic anydride is a common acetylation compound, used for the production of modified starches (E1414, E1420, E1422)

Phosphoric Acid

SYNONYMS: Orthophosphoric acidFORMULA: H3PO4Pure anhydrous phosphoric acid is clear,

odourless, colourless, non-volatile, rather viscous, syrupy liquids. With the CAS registry number 7664-38-2,it is also called orthophosphoric acid. Phosphoric acid is easily soluble in water and soluble in alcohol.

PREPARATION: This very pure phosphoric acid is obtained by burning elemental phosphorus to produce phosphorus pentoxide and dissolving the product in dilute phosphoric acid.

USES: Catalyst in the synthesis of Acetaminophen

Other uses:Phosphoric acid is mainly used in the

manufacture of various phosphate, such as ammonium phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, trisodium phosphate, etc and condensation phosphate class.

In medical field, phosphoric acid is used in the manufacture of glycerin sodium phosphate, iron phosphate. At the same time, as an etching solution, phosphoric acid is to used to clean and roughen the surfaces of teeth where dental appliances or fillings will be placed. Phosphoric acid is also used in many teeth whiteners to eliminate plaque that may be on the teeth before application.

Food-grade phosphoric acid (additive E338) is used to acidify foods and beverages such as various colas because of its sour intensity.

In feed field, phosphoric acid is used to make chemical fertilizer as calcium hydrogen phosphate.

Ethanol SYNONYMS: ethyl alcohol, Pure alcohol,

Grain alcohol, or Drinking alcoholFORMULA: C2H6OEthanol is a volatile, colorless liquid that has

a slight odor. It burns with a smokeless blue flame that is not always visible in normal light.

Ethanol is a versatile solvent, miscible with water and with many organic solvents, including acetic acid, acetone, benzene, carbon tetrachloride, chloroform, diethyl ether, ethylene glycol, glycerol, nitromethane, pyridine, and toluene.[24][26] It is also miscible with light aliphatic hydrocarbons, such as pentane and hexane, and with aliphatic chlorides such as trichloroethane and tetrachloroethylene

PREPARATION:

Ethanol for use as an industrial feedstock or solvent (sometimes referred to as synthetic ethanol) is made from petrochemical feed stocks, primarily by the acid-catalyzed hydration of ethylene, represented by the chemical equation

C2H4 + H2O → CH3CH2OHUSES: Solvent

Other uses: Ethanol is used in antiseptic and

some antibacterial soaps and wipes. Ethanol is effective against viruses, fungi and most bacteria but is ineffective against bacterial spores.

Ethanol is considered a ‘feedstock’ into the chemical industry as it is used to make other important chemicals.

PROCEDURES

1. Fill 400 mL beaker about half full with water and place it on a hot plate and boil.

2. Weigh 1.5g p-aminophenol and transfer into 250 mL Erlenmeyer flask. (Avoid contact with skin. You may wear gloves.)

3. Add 25mL water then add 20 gtts conc. phosphoric acid, and swirl flask until all of the amines dissolves. (If not, add few more drops of phosphoric acid)

4. Turn off the hot plate. Place flask in hot water then add 2mL acetic anhydride. Leave the flask for 10mins.

5. Remove flask and place it on ice-water bath. Stir mixture to crystallize acetaminophen. (You may need to scratch the walls of the flask to start the crystallization. If no crystals appear, add small seed of acetaminophen to start the crystal formation. Allow the flask to stay in the ice-water bath for 30 minutes)

6. Collect crystals in Bunchner funnel using vacuum filtration.

7. Wash crystals with 10mL cold water allowing crytals to dry.

8. Determine the mass of crude acetaminophen.

Recrystallization of the Acetaminophen

1. Place crude acetaminophen in 100mL beaker. Add 200mL water and heat on a hot plate until dissolve. NOTE: If solution boils and crystals remain, add another 10mL water.

2. Remove beaker and allow the solution to cool. When crystals begin to appear, place beaker in an ice bath for 20mins. NOTE: if no crystals appear, scratch the inside walls of beaker

3. Collect crystals using Bunchner filtration apparatus, wash with 10mL water.

4. Transfer the filter paper and crystals to a watch glass and let it dry.

5. Determine the mass of the purified acetaminophen.

Determining the Melting point of the sample

1. Fill the capillary tube to a depth of 0.2 cm with the recrystallized Acetaminophen

2. Place the capillary tube in the melting point apparatus then determine.

3. Melting point of acetaminophen is 169-171 degree C, p-aminophenol melts at 189-190 degree C.

4. The Acetaminophen should be labeled with the name of the group, the mass of aspirin, the percent yield and its melting point.

NOTE: Don’t use the acetaminophen obtained for a headache. The purity is not assured.

 

USES OF ACETAMINOPHEN

USES OF ACETAMINOPHEN

ANALGESIC

ANTIPYRETIC

•Unlike aspirin and salicylates they do not cause ulceration and bleeding. 

•they have little or no anti-inflammatory properties.

ANSWERS TO QUESTIONS

CHEMICAL NAME OF PHENOL:

N-Acetyl-P-Aminophenol (APAP)

STRUCTURAL ACTIVITY RELATIONSHIPS OF ACETAMINOPHEN:

DOSES OF ACETAMINOPHEN:

It should be taken every 4-6hrs/ prn or as directed by a doctor.

500mg Tablet: Adult and Pedia > 12 yrs: 1tab q 4-6hrs or prn

250mg/5mL suspension: Adult and Pedia > 12yrs: 2tsp; 7-12yrs: 1 ½ tsp; 3-6yrs: ½ to 1 tsp; 1-2 yrs: ½ tsp

****CAUTION: Do not take more than 4g(equivalent to 8tablets) in a 24-hr period.

MECHANISM OF ACTION:- Paracetamol decreases fever by

inhibiting the effects of pyrogens on the hypothalamic heat regulating center and by hypothalamic action leading to sweating and vasodilation.

- Relieves pain by inhibiting prostaglandin synthesis at the CNS but does not have Anti-inflammatory action because of its minimal effect on peripheral prostaglandin synthesis.

CAUTION WITH THE USE OF ACETAMINOPHEN

AND TOXIC METABOLITE PRODUCED:- Acetaminophen is Hepatotoxic

and Renal toxic.- The toxic metabolite produced

from acetaminophen is O-Sulfates/O-Glucorinides which is slowly rearranged to form the reactive NAPQI (N-acetyl-p-benzoquinone imine) metabolites.

PACKAGING AND STORAGE

REQUIREMENTS- They may be packed in a blister

packaging, tightly-closed container and CRC’s.

- Product should be kept out of reach and sight of children, and should not be stored above 30OC.

LIMITATIONS OF THE USE OF

ACETAMINOPHEN AS ANALGESIC-ANTIPYRETIC- If the patient is allergic to

Paracetamol or any ingredient in the product.

- Long term use should be avoided in patients with anaemia or with heart, lung, kidney, or liver disease.

- Should not be used more than 4g/ day.- Should not be used by chronic

alcoholic patients.

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