Synthesis of Aspirin

Purpose: To synthesize aspirin, a common analgesic drug, via nucleophilic acid-catalyzed substitution reaction of salicyclic acid with acetic anhydride. The whole reaction is catalyzed by phosphoric acid. (The experiment involved three parts: The synthesis of aspirin, the isolation and purification of aspirin, and the estimation of the purity of the final product. ) [pic] Procedure[1]:

A mixture of salicylic acid (0.21g, 1. 52 mmol) and acetic anhydride (0. 52g, 5. 1mmol, 0. 48 ml) with one drop of concentrated phosphoric acid in a conical vial was heated (50oC) till salicylic acid was dissolved while stirring (conical vial was added with a magnetic spinvane and attached with an air condenser). The solution was then heated for another 10 minutes and cooled to room temperature while the air condenser and spinvane was removed.

The solution was left to crystallize in a beaker of crushed ice while water was added (3. 0mL). The crystals were collected by vacuum filtration and washed with cold water (2 x 1. 0mL) then let dry to yield aspirin (0. 1732, 63%) as solid form. Mp. 133-136 oC (lit[2] 134-136 oC). Discussion: The reaction of synthesis of aspirin with salicylic acid an acetic anhydride with phosphoric acid as catalyst formed acetylsalicylic acid in 63% yield as crystalline solid.

The melting point of the crystals was determined to be 133-136 oC, which is within the reported literature range and supports the identity of the desired reaction product. The narrow range of the melting point indicated the purity of the compound. The reaction yield may be improved by adjusting the amount of reactant or product in the reaction. For instance, by increasing the amount of acetic anhydride reactant, the reaction equilibrium will favor the product, which will produce a greater amount of aspirin crystals.

Or, by removing the acetic acid product, the reaction equilibrium will favor the product to increase the yield of aspirin. Percent yield may also be increased by increasing the temperature and amount of catalyst. Both would serve the purpose of higher energy and produce more product as crystals [1] Callam, Christopher.

Organic Chemistry Lab- Chemistry 254, Iowa: McGraw Hill, 2008-2009, 115-120. 2 Gokel, George W. Dean’s Handbook of Organic Chemistry: McGraw Hill, 2004, 135.

Aspirin is prepared by the esterification of salicylic acid with acetic anhydride under acidic conditions. The phenol group in salicylic acid is replaced by a carboxyl group through electrophilic substitution. The mechanism for the reaction can be summarized as follows: …

Once the aspirin is prepared, it is isolated from the reaction solution and then it is purified. The aspirin is insoluble in cold water, and it is isolated by filtering the chilled reaction solution. Purification is essential to remove any …

The Preparation of Aspirin The purpose of this experiment is to synthesize aspirin (acetyl salicylic acid) from salicylic acid and acetic anhydride. CO2H OH salicylic acid 2g 0. 014 mole O O O CH3 H2SO4 ethyl acetate CO2H O O …

Aspirin is most widely sold over-the-counter drug. It has the ability to reduce fever (an antipyretic), to reduce pain (an analgesic), and to reduce swelling, soreness, and redness (an anti-inflammatory agent). Much of this is believed to be due to …

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