Experiment 14 Preparation of Acetylsalicylic Acid

Objectives Obtain experience in Organic Synthesis To isolate and purify your synthesized product Gain experience in organic chemistry techniques

Aspirin The pharmaceutical ingredient in Aspirin tablets is acetylsalicylic acid Synthesized from salicylic acid

Aspirin Known since around 500 BC Bitter powder extracted from willow bark that could ease pain In the 1700s chemists elucidated that the chemical responsible was salicin

Aspirin When consumed, salicin is metabolised to salicylic acid Salicylic acid is the active ingredient

Aspirin In 1829 Leroux showed that the active ingredient was salicylic acid Used for years to treat pain, swelling and fevers However not ideal as caused irritation to user’s stomach High doses caused bleeding

Aspirin Hoffmann reasoned the irritation was due to the phenol group Converted salicylic acid to acetylsalicylic acid Derivative reduced fever, pains and swelling, was less irritating Worked even better than salicylic acid

How does Aspirin work? Dr. J.Vane – won 1982 Nobel Prize for Medicine for his discovery prostaglandins Pain signals are relayed to the brain from nerve endings by chemicals called prostaglandins cyclooxygenase-2 Aspirin inhibits the synthesis of these neurotransmitters by an enzyme called cyclooxygenase-2

How does Aspirin work? Cyclooxygenase-2 is responsible for pain transmission Cyclooxygenase-1 is responsible for maintenance of the gastric lining Aspirin affects both enzymes Lead to development of other pain killing drugs

Actions of Aspirin Analgesic - kills pain Antipyretic – lowers temperature Prevents blood clots by inhibiting platelet aggregation Lowers blood pressure Anti-inflammatory – treatment of arthritis/swelling

Acetylation Reaction One of many ways by which this acetylation can be achieved

Acetylation Reaction

Experimental Mix 1.0g of salicylic acid and 2ml of acetic anhydride in a 50ml flask and add 5 drops of conc. H 2 SO 4 Heat on the steam bath for 10 mins* Allow to cool – crystallization Cool in ice to ensure complete crystallization of the acetylated product - add 15ml water*

Experimental Isolate the crystals on the Hirsch funnel Wash with cold water (5-10ml) Transfer crystals to a beaker Add 15ml of 5% aq NaHCO 3 * Filter the solution of the sodium salt of aspirin through a fluted filter paper

Experimental Pour solution on to 5ml of 3M HCl Acetylsalicylic acid precipitates Filter the crystals on the Hirsch funnel Recrystalize from ethanol/water soln. Isolate crystals, allow to dry, get melting point and % yield