Lachrymtory agent -
To synthesize aspirin, a common analgesic drug. The experiment actuallyinvolves three parts: The synthesis of aspirin, the isolation and purification of aspirin,and the estimation of the purity of the final product.
The synthesis involves the reaction of salicylic acid and acetic anhydride inthe presence of a catalyst, phosphoric acid, H
. Which will keep the aspirin frombeing hydrolyzed.
Isolation and Purification:
Once the aspirin is prepared it must be isolated from thereaction solution and purified. The aspirin is insoluble in cold water, and can be isolatedby filtering the chilled reaction solution. Purification is necessary to remove anyunreacted salicylic acid and acetic anhydride, as well as the acetic acid product andphosphoric acid. Acetic anhydride is caused to decompose by the addition of water oncethe formation of aspirin is complete:The acetic acid and phosphoricacid are water soluble and can beremoved by washing the aspirinwith chilled water. Salicylic acid isonly slightly soluble in water and isnot completely removed in the washing step. Final purification is accomplished by theprocess of
The impure aspirin is dissolved in warm ethanol. Thesolution is then cooled slowly, and the aspirin crystallizes out of solution leaving thesalicylic acid and other impurities behind.
Estimation of Purity:
The melting point of a compound can be used to identify it andalso to estimate its purity. Generally an impure compound will exhibit a melting pointwhich is lower than that of the pure compound. Therefore, if your aspirin melts at atemperature below the accepted melting point two possibilities exist: either your productis impure or it is not aspirin. A pure substance will melt sharply over a range of 1 or 2degrees celcius. That is, the temperature at which melting first occurs is only 1 or 2degree less than the temperature at which the sample is completely melted. An impurecompound will melt over a wider temperature range.
This experiment uses salicylic acid, acetic anhydride andphosphoric acid. The salicylic acid and aspirin may cause irritation to your skin or eyes,but are basically not hazardous. An excess of these can be disposed of in the sink or if packaged, in the trash. If you spill some, wipe it up with a wet paper towel and throw thetowel in the trash. The acetic anhydride and phosphoric acid can cause bad burns. Usethem in the hood. Be sure to wear gloves and safety goggles when using thesechemicals. Excess chemicals must be disposed of in the plastic tub of water. This willconvert the acetic anhydride to vinegar and dilute the phosphoric acid. If you spill a lot of either of these, notify your instructor.
1.Weigh out 3.0 g of salicylic acid and place in a 250 ml Erlenmeyer flask.2.Measure out 6.0 ml of acetic anhydride and add this to your flask. Be sureto do this in the hood and wear your goggles.Don't let the acetic anhydride contact your skin and don't get the vapors inyour eyes.3.Still in the hood, Carefully add 5 to 10 drops of 85% phosphoric acid, acatalyst, to the flask and swirl to mix everything thoroughly.
Still in the hood, heat the mixture for about 10 min. in a beaker of warmwater (70-80
C).5.After heating, cautiously add 20 drops of distilled water.6.Next add 20 ml of distilled water and cool in an ice bath. You can do this atyour bench. If crystals do not appear, you can scratch the walls of the flaskwith a stirring rod to induce crystallization.7.Filter the solid aspirin through a piece of pre-weighed filter paper using aBuchner funnel and the aspirator. Wash the crystals with 2-3 ml of chilledwater. The liquid is mostly water and can be washed down the sink. Allowthe air to be drawn through the solid and filter paper for 15 minutes. Besure to record the filter paper weight in your notebook.8.Preweigh a watch glass, and place the filter paper with the product on itand weigh. Obtain the weight of the aspirin by subtracting the weights of the filter paper and the watch glass from the total weight.9.At this point the aspirin contains traces of water and salicylic acid, andfurther purification is required. Place a small amount of this impure aspirinin a small labeled beaker, cover with a tissue, and set aside to dry untilnext week. The amount to be placed in the beaker, enough to measure amelting point, will be indicated by the instructor.
transfer the remainder of the impure aspirin to a 100 mL beaker. Add 10mL of 95% ethanol to the beaker and warm (do not boil) the mixture in awater bath to dissolve the crystals. If the crystals do not all dissolve, add 5mL more of the ethanol and continue to warm the mixture. When thecrystals are all dissolved, add 20 mL of warm water, cover the beaker witha watch glass, and let the solution cool slowly. Crystals of aspirin will form.Complete the
by cooling in an ice bath.11.Collect the purified aspirin by filtration as before. Dry the crystals by pullingair through them for about 15 minutes. Put the product into a small beaker,cover with a tissue, and set aside to dry further until next week.12.Measure the melting points of both the impure aspirin, and therecrystallized aspirin.http://wwwchem.csustan.edu/consumer/aspirincons/aspirincons.htm
Synthesis of Aspirin (Acetylsalicylic Acid)Background
Aspirin is a trade name for acetylsalicylic acid, a common analgesic. Acetylsalicylic acidis an acetic acid ester derivative of salicylic acid. The earliest known uses of the drugcan be traced back to the Greek physician Hippocrates in the fifth century B.C. He usedpowder extracted from the bark of willows to treat pain and reduce fever. Salicin, theparent of the salicylate drug family, was successfully isolated in 1829 from willow bark.Sodium salicylate, a predecessor to aspirin, was developed along with salicylic acid in1875 as a pain reliever. Sodium salicylate was not often popular though, as it has ahabit of irritating the stomach. However, in 1897, a man named Felix Hoffman changedthe face of medicine forever. Hoffman was a German chemist working for Bayer. He hadbeen using the common pain reliever of the time, sodium salicylate, to treat his father'sarthritis. The sodium salicylate caused his father the same stomach trouble it causedother people, so Felix decided to try and concoct a less acidic formula. His work led tothe synthesization of acetylsalicylic acid, or ASA. This soon became the pain killer of choice for physicians around the globe. Scientists never really understood the inner workings of the drug however. It wasn't until the 1970's, when British pharmacologistJohn Vane, Ph.D. began work on aspirin that people began to understand how aspirinreally works. Vane and his colleagues found that aspirin inhibited the release of ahormone like substance called prostaglandin. This chemical regulates certain bodyfunctions, such as blood vessel elasticity and changing the functions of blood platelets.Thus can aspirin affect blood clotting and ease inflammation.
The reaction for synthesis of acetylsalicylic acid is shown in the following figure.In previous experiments, we used Fischer esterification reaction to produce some estersthat we detected by odor. The current experiment uses, instead of glacial acetic acid(concentrated acetic acid), another carboxylic acid derivative, acetic anhydride for ester formation. The advantage of using acetic anhydride is that you do not produce water which can be used for hydrolysis of the newly formed ester. Concentrated phosphoricacid will be used to keep everything in the acidified, protonated state. Acetic anhydrideis the preferred acid derivative to synthesize aspirin commercially because the aceticacid produced in this reaction can be used again, by converting it back into aceticanhydride.In a 125-mL erlenmeyer flask, add 2 g salicylic acid (put the flask on the balance, andzero it). In the hood, carefully add 5 mL of acetic anhydride (severe irritant, handlecarefully) to the flask. Slowly add about 10 drops of 85% phosphoric acid (H
). Stir the mixture with a stirring rod. Place the flask and its contents in a boiling water bathand stir untill all the solid dissolves. Remove the flask from the hot water and let it cool.Working in the hood, add 20 drops of water to the cooled mixture. (Avoid breathing anyof the vapors, which contain acetic acid, and are irritating).When the reaction is complete, add 50 mL of cold water to the reaction mixture. Coolthe mixture by placing the flask in an ice bath for 10 minutes. Stir occassionally.Crystals of aspirin should form. If no crystals form, gently scratch the sides of the flaskwith the stirring rod.Collect the aspirin crystals using a Buchner funnel. Set up a Buchner funnel asdescribed by your instructor, or in a manner performed previously. Add a pre-weighedfilter into the funnel and wet it so that it seals completely when vacuum is applied. Pour the aspirin crystals into the funnel and collect the white solid. Add a little cold water tothe flask and make certain all the crystals are transferred to the funnel. After you havewashed the crystals, keep the vacuum on for about 5 min to help dry the crystals. Turnoff the vacuum, and transfer the filter paper and crystals to a pre-weighed beaker. Letthis material sit at room temperature until the next lab period when you will determineyour aspirin recovery.
1.Based on the mass of salicylic acid (~2 g) determine the maximum yield of aspirin (theoretical yield) from this amount of starting material.
Note: based on the molar masses in the table below, 138.12g of salicylic acid would produce a maxium (theoretical) of 180.16 grams of aspirin (1 mole salicylic acid produces 1mole aspirin). You will not use 1 mole of salicylic acid.Therefore, your calculation must be based on the amountyou actually use. It is easy to do a proportion calculation.Your instructor can help you.2.Calculate the mass of crude aspirin that you collected.
Calculate the percent yield of aspirin =
[amount collected / theoreticalyield] x 100%
What is the melt point of your dried aspirin? Pure aspirin has a melt pointof 135
C. Compare the melting points of your aspirin and pure aspirin.
Synthesis of AspirinINTRODUCTION
Aspirin (acetylsalicylic acid) is a synthetic organic derived from salicylic acid. Salicylicacid is a natural product found in the bark of the willow tree and was used by the ancientGreeks and Native Americans, among others, to counter fever and pain. However,salicylic acid is bitter and irritates the stomach.A German chemist named Felix Hoffman is credited with being the first to synthesizeaspirin in 1897. Hoffman's father had severe arthritis but could not tolerate salicylic acidhe was taking for pain relief. The name given for Hoffman's new compound was
. Apparently this comes from acetylation (
), together with
, part of thename for Meadow-sweet (Spiraea ulmaria), a plant rich in salicylates.