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Synthesis of Aspirin
Learning Goals
1. To synthesize aspirin from salicylic acid and acetic anhydride. 2. To purify the crude product by Recrystallization.

Introduction
Most drugs are chemical compounds which are described as "organic compounds" because they are comprised primarily of the elements carbon, hydrogen and oxygen. The present experiment will be the synthesis of a familiar organic compound called aspirin. The common chemical name is acetylsalicylic acid. spirin, the most widely used drug in the world, has an interesting history. !early 2"## years ago, $ree%s reported that extracts of willow and poplar bar% could be used to relie&e pain and symptoms of illness. There are reports that merican 'ndians, before the time of (olumbus, used special teas made from the bar% of willow trees to reduce fe&er. 'n 1)*+, the Re&erend ,dward -tone introduced these extracts and teas to the ,uropeans and in the early 1.##/s the acti&e ingredient in willow bar% 0and in the flowers of the meadow sweet plant which had similar therapeutic characteristics1 was isolated and identified as salicylic acid 0from salix, the 2atin name for the willow tree1. lthough salicylic acid could be synthesized in the laboratory and large 3uantities became a&ailable for therapeutic use in the mid 1.##s, the compound/s acidic properties caused irritation in the moist membranes of the mouth, throat and stomach. 'n 1.)", the sodium salt was introduced and although the salt was less sour to the taste 0actually it had an ob4ectionable sweetish taste1, it did not alle&iate the gastric discomfort problems.

salicylic acid

sodium salicylate

'n 1.5+, 6elix 7offman 8r., a chemist wor%ing for the 9ayer 2aboratories in $ermany, disco&ered a practical route for synthesizing an ester deri&ati&e of salicylic acid, acetylsalicylic acid.

cetyl-alicylic cid spirin, -

:) cetylsalicylic acid, a wea%er acid than salicylic acid, was found to ha&e the medicinal properties of salicylic acid without ha&ing the ob4ectionable taste or producing the stomach problems. The acetyl group effecti&ely mas%s the acidity of the drug during its ingestion and after it passes into the small intestine, it is con&erted bac% to salicylic acid where it can enter the bloodstream and do its pain relie&ing action. 9ayer called its new product "aspirin," the name being deri&ed from "a" for acetyl, and the root "-spir", from the 2atin name Spiraea ulmaria, the meadow sweet flower, from which salicylic acid had been isolated. 't was patented by 9ayer in 1.55, and in 151" 9ayer spirin tablets became commercially a&ailable as a non; prescription drug. The trademar% is still owned by the 9ayer .$. company in $ermany. Today, aspirin is one of the most widely used, commercially a&ailable pharmaceutical drugs in the world. 'ts properties ma%e it a powerful analgesic 0pain relie&er1, antipyretic 0fe&er reducer1 and anti;inflammatory 0reduces swelling1 drug. spirin is not without its faults. 't still causes some stomach irritation in some indi&iduals, and it has been estimated that about 1 m2 of blood is lost from the stomach lining for each gram of aspirin consumed. spirin is %nown to interfere with normal blood clotting 0which actually may be a benefit in pre&enting heart problems1. Reye syndrome, a rare but serious illness has been associated with aspirin, and children and teenagers should not use aspirin for flu li%e symptoms before consulting a doctor.

Synthesis
The salicylate ion forms the therapeutic part of the aspirin. spirin passes through the acidic stomach contents ad does not ionize and form the salicylate ion until it reaches the al%aline conditions in the intestines. 7ere it is hydrolyzed to form the acetate and salicylate ion. The latter ion is absorbed through the intestinal wall. The e3uation depicting this reaction is gi&en below.
H3C O OH O Aspirin O OH O H O O Salicylate ion acetate ion O

H3C

H2O

The final step in the commercial synthesis of aspirin in&ol&es the re&erse of this reaction. The salicylic acid is treated with acetic anhydride, which is a more reacti&e compound than the acetate ion. (atalytic amounts of sulfuric acid ma%e the reaction proceed &ery rapidly. This is the synthesis step you will perform in this assignment.

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72-<: 102.01 g/mol 138.1 g/mol 180.2 g/mol The abo&e reaction is an example of an organic synthesis called esterification. ,sterification is the acid catalyzed reaction of a carboxyl 0;(<<71 group and an ;<7 group of an alcohol or phenol to form a carboxylate ester. 'n the synthesis of aspirin the ;<7 group is the phenolic -OH group attached to ring of the salicylic acid. The acetyl group, -COCH3 comes form acetic anhydride, and the reaction is catalyzed by sulfuric acid. This reaction is 3uite simple and gi&es a good yield of the product. spirin, although it is soluble in hot alcohol, is not soluble in water. (onse3uently, the final product will be filtered from an a3ueous solution, and washed with cold water, then air dried.

A Special Summary (Song)

"7ow to Ma%e spirin Today"

chey day, headache please, go away. nd '/m getting a fe&er, <y &ey= (an you tell me how to ma%e, how to ma%e aspirin today> These you ta%e, when aspirin you ma%e. -alicylic acid/s on the list nd acetic anhydride and an acid catalyst. -ulfuric to be exact. Mix them all and they react, nd an ester is formed. ?ou esterify. ?ou esterify. <n phenol, acetyl finds its goal. nd from water, white crystals arise. nd to ma%e them pure, from alcohol recrystallize.
by ho!as Ott Oa"land #ni$ersity, %ochester &I

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Experimental 'reparation of Aspirin(

1; @lace +.# g 0#.#2 mol1 of salicylic acid in a 1## m2 ,rlenmeyer flas%. 2; dd, with continuous stirring, * m2 of acetic anhydride 0fume hood1 followed by 1 m2 of concentrated sulfuric acid. +; -tir the mixture gently obser&ing the rise in temperature to )#;.# A( while the salicylic acid dissol&es. 7eat in a water bath if needed. :; fter 1" minutes the solution cools by itself to +";:" A( and a solid mass of aspirin forms. "; @our +" m2 of ice;cold water o&er the contents of the flas% to hydrolyze excess acetic anhydride and to complete the precipitation of aspirin. *; (hill the ,rlenmeyer flas% in an ice bath with occasional swirling to cause precipitation of the product. 'f no precipitate forms, scratching the side of the flas% with a glass stirring rod may help initiate crystallization. Bhile the flas% is chilling, prepare a &acuum filtration apparatus as shown at the right. ); (ollect the crude aspirin using a 9uchner funnel and wash with ice;cold water. .; ir;dry the product, weigh, and calculate the yield.

%ecrystalli)ation of Crude Aspirin(

To purify your synthesized aspirin, transfer it to a small erlenmeyer flas% and add a small amount of ethanol using a plastic pipet. Barm the solution to *# C(. (o&er the solution and allow it to cool undisturbed to room temperature. Then set the bea%er in an ice bath and once again scratch the inside of the flas% with a glass rod to induce recrystallization. (ollect the purified aspirin by &acuum filtration and wash them with ice;cold water. 2et the crystals dry for a few minutes before weighing them. Determine the mass of your dry purified aspirin.

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Synthesis and Analysis of Aspirin Report -heet

!ameF ;;;;;;;;;;;;;;;;;;;;;;;;;;

$i&e a balanced e3uation for the synthesis of aspirin from salicylic acid and acetic anhydride.

Determine the limiting reagent in the synthesis reaction 0show calculations1.

'reparation of Aspirin( Theoretical yield of aspirin 0-how calculations1.

ctual yieldE @ercentage yield 0show calculations1.

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%ecrystalli)ation of Aspirin( Mass of crude aspirinE Mass of recrystallized aspirinE @ercentage yieldE

$i&e the mechanism of the reaction in your experiment.