The Synthesis and Analysis of Aspirin Acetylsalicylic acid is the chemical name for aspirin, the ubiquitous pain reliever. One of the compounds used in the synthesis of aspirin is salicylic acid, which is itself a pain reliever that was known to many ancient cultures, including the Native Americans who extracted it from willow tree bark. Salicylic acid is extremely bitter tasting, and frequent use can cause severe stomach irritation. he search for a milder form of this pain reliever led to the successful synthesis of acetylsalicylic acid by the !erman chemist "elix #offmann in $%&'. (our (our two primary ob)ectives in this experiment will be to synthesi*e and analy*e an aly*e aspirin. here is more than one way to synthesi*e aspirin+ in this experiment, you will react acetic anhydride with salicylic acid in the presence of phosphoric ph osphoric acid which acts as a catalyst-. he reaction equation is shown below. HO
HO
O
O
OH
+ Sa Salicylic acid
H3C
O
O
O
O
H 3P O 4 (a q ) CH3
Acetic anhydride
CH3
∆
O
O
Acetylsalicylic acid
+
H3C
OH
cetic acid
(ou (ou will conduct two tests of your synthesis to verify that you did indeed make aspirin, and to determine its relative purity. purity. "irst, you will measure the melting temperature of a sample of your product, using a elt Station. Second, you will use a Spectrophotometer to test the absorbance of salicylic acid impurity in your aspirin sample after it has been complexed with "e'/ from iron 000- nitrate solution.
OBJECTIVES 0n this experiment, you will • • • •
Synthesi*e a sample of acetylsalicylic acid aspirin-. 1alculate the percent yield of your synthesis. easure the melting temperature of your aspirin sample. 1onduct a spectrophotometric analysis of your aspirin sample.
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MATERIALS Part I Synthesis Materials
23 m4 5rlenmeyer flask two $3 m4 graduated cylinders 92 m4 graduated cylinder 923 m4 beaker :;chner funnel, filter, and filter paper spoon, spatula, or rubber policeman ice bath hot plate plastic :eral pipet or eyedropper
solid salicylic acid %26 phosphoric acid solution, #'7O8 liquid acetic anhydride distilled water cold distilled water balance emperature 7robe or thermometer watch glass
Part II Melting Temperatre
4abernier elt Station glass capillary tubes, one end closed
aspirin crystals from 7art 0tissues preferably lint=freemortar and pestle optional-
Part III Spe!trophotometri! A"sor"an!e
4abis 7lus spectrophotometer 23 m4 graduated cylinder plastic cuvette with lid 923 m4 beaker $33 m4 beaker
salicylic acid aspirin crystals from 7art 0ethanol, denatured 3.392 iron 000- nitrate solution, "eNO'-' distilled water $33 m4 volumetric flask 923 m4 volumetric flask
PROCE#$RE Part I Synthesi%e Aspirin
$. Obtain and wear goggles. 7rotect your arms and hands by wearing a long=sleeve lab coat and gloves. 1onduct this reaction in a fume hood. 9. easure out 9.3 g of salicylic acid into a 23 m4 5rlenmeyer flask. '. Add 2.3 m4 of acetic anhydride and 2 drops of %26 phosphoric acid solution. Swirl the mixture. 0f necessary, use a sparingly small amount of distilled water to rinse down any bits of solid that may be on the inner walls of the flask. CAUTION: Handle the phosphoric acid and acetic anhydride with care. Both substances can cause painful burns if they come in contact with the skin. 8. (ou are now ready to begin the synthesis of aspirin. a. 7repare a ?3@%31 hot=water bath using a 923 m4 beaker on a hot plate. onitor the water temperature using a emperature 7robe or thermometer. b. #old and partially submerge the 23 m4 flask and contents in the water bath. c. #eat the mixture in the hot=water bath for $2 minutes, or until the mixture ceases releasing vapors. Stir the mixture occasionally during heating. Add 9 m4 of distilled water about $3 minutes into the heating.
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Organics Chemistry with Vernier
The Synthesis and Analysis of Aspirin
2. Next you will crystalli*e the aspirinB a. Chen you are confident that the reaction has reached completion no vapors appearing-, carefully remove the flask from the hot plate an d add 93 m4 of distilled water. b. Allow the mixture to cool to near room temperature. ransfer the flask to an ice bath for about five minutes. As the mixture cools, crystals of aspirin should form in the flask. D. Now you will wash the synthesi*ed aspirinB a. Set up a vacuum filtration using a :;chner funnel. :e sure to weigh and record the mass of the filter paper to the nearest 3.3$ g before filtering the solid. b. ransfer the contents of the flask to a :;chner funnel assembly. "ilter the mixture with vacuum suction. c. Chen most of the liquid has been drawn through the funnel, turn off the suction and wash the crystals with 2 m4 of cold, distilled water. d. After about $2 seconds, turn the suction back on. Cash the crystals with cold, distilled water twice more in this manner. e. !ently transfer the filter paper with your product onto the watch glass to air dry. As directed by your instructor, either direct a gentle stream of air low flow- to help d ry the solid, or let them air dry until the next lab period. f. Ceigh the dried recrystalli*ed product on the filter paper and record the mass to 3.3$ g. ?. Eetermine the mass of your dry aspirin sample and record in the data table. Part II Test the Melting Temperatre of an Aspirin Sample
%. 7repare a sample for meltingB a. Fse a mortar and pestle to pulveri*e a small amount about 3.9 g- of your synthesi*ed aspirin and place it in a small pile in the mortar. b. 7ack a capillary tube '@8 mm G$H% inch- deep with your aspirin sample by inserting the open end into the small pile of aspirin. A small amount of the solid will be pushed up into the tube. c. ap the closed end of the capillary tube on the table top to compress the sample into the closed end. d. 1heck the control knob on the elt Station to confirm that it is in the Off position. e. 1arefully insert the capillary tube of solid into one of the sample holders of the elt Station. &. 1onnect the elt Station power supply to a powered electrical outlet. $3. 1onnect the elt Station sensor cable to 4ab
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c. 1arefully observe your sample. Chen the solid begins to melt, click ark to mark the temperature on your graph or press the D key on the computer or the OK button on 4ab
(our synthesis converted most, but not all, of the salicylic acid into acetylsalicylic acid. (ou will mix iron 000- nitrate with salicylic acid in your aspirin sample to complex the salicylic acid, which is a bluish=purple color. (ou will analy*e several samples to determine the amount of salicylic acid impurity in your synthesi*ed aspirin. (ou can use this information to calculate the purity of your aspirin sample. "ollow Steps $D@9$ to prepare a set of salicylic acid standard solutions and conduct testing to develop your own :eerIs law plot of the standards. Steps 99 @92 will guide you through the set up and testing of your aspirin sample. $D.
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Organics Chemistry with Vernier
The Synthesis and Analysis of Aspirin
d.
Standard salicylic acid solution from Step 17 a! (m")
#ater (m")
1
1$%$
$
&
'%$
&%$
3
%$
4%$
4
4%$
%$
&%$
'%$
$%. Eisconnect the elt Station and connect the Spectrophotometer to the FS: port of 4ab
Organic Chemistry with Vernier
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c. 1hange the mode to 5vents with 5ntry absorbance vs. concentration- and select a wavelength for analysisB 0n 4ab
(ou are now ready to collect data for the five standard solutions. a. 4eave the rial $ cuvette in the Spectrophotometer and start data collection. b. Chen the absorbance value displayed on the screen has stabili*ed, select Keep and enter the molar concentration. Select OK. he absorbance and concentration values have now been saved for the first solution. c. Eiscard the cuvette contents as directed by your instructor. Fsing the solution in the second $33 m4 volumetric flask, rinse the cuvette twice with G$ m4 amounts, and then fill it 'H8 full. Cipe the outside, place it in the device, and close the lid. After closing the lid, wait for the absorbance to stabili*e and select Keep. 5nter the molar concentration, and select OK. d. Lepeat the procedure for the remaining salicylic acid solutions that you prepared. e. Stop data collection to view a graph of absorbance vs. concentration. f. Lecord the absorbance and concentration values in your data table. (ou can do this either by examining your data points along the curve, or by viewing the data table. g. 1hoose 1urve "it from the Analy*e menu. h. 1hoose 4inear as the "it 5quation. Select OK. he graph should indicate a direct relationship between absorbance and concentration, a relationship known as :eerIs law. he regression line should closely fit the five data points and pass through or near- the origin of the graph. i. After the preparation and testing of your aspirin sample in the following steps, you will be instructed to interpolate along this plot to determine the concen tration of salicylic acid impurity in your aspirin sample.
99. 7repare the synthesi*ed aspirin sample for testing. 1omplete this step quickly and be ready to proceed directly to Step 9'. a. easure out about 3.8 g of aspirin and transfer it to the 923 m4 beaker. Lecord the mass of aspirin that you use to the nearest 3.3$ g. b. Add $3 m4 of ethanol to the beaker of aspirin sample. Swirl the mixture to dissolve the solid. c. Add $23 m4 of distilled water to the beaker. ix the solution. d.
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Organics Chemistry with Vernier
The Synthesis and Analysis of Aspirin
9'. easure and record the absorbance value of the treated aspirin sample. his must be done within $3 minutes of completing Step 99. o do thisB a. Linse and fill the cuvette 'H8 full with the sample. 1ap the cuvette and place it in the Spectrophotometer. b. onitor the absorbance value on the displayed eter in 4ogger Pro or tap the eter tab in 4ab
#ATA TABLE Part I Synthesis of Aspirin *ass of salicylic acid used (+) ,olume of acetic an-ydride used (m") *ass of acetic an-ydride (1%$' +.m") used (+) *ass of aspirin and filter paper (+) *ass of filter paper (+) *ass of aspirin synt-esi/ed (+) Part II Melting Temperatre #ata *eltin+ temperature ran+e (0C) Part III Sali!yli! A!id Standard Sto!& Soltion nitial mass of salicylic acid (+) *oles of salicylic acid (mol) nitial molarity of salicylic acid (mol.")
Organic Chemistry with Vernier
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Part III Beer's La( #ata for Sali!yli! A!id Standard Soltions Trial
Concentration (mol.")
2!sor!ance
1 & 3 4 Test of the Prity of the Synthesi%ed Aspirin nitial mass of aspirin sample (+) 2!sor!ance of aspirin sample Concentration of salicylic acid (mol.") *oles of salicylic acid in aspirin sample (mol) *ass of salicylic acid in aspirin sample (+) *ass of aspirin in sample (+) Percent aspirin in sample ()
#ATA A)AL*SIS $. Chat is the theoretical yield of aspirin in your synthesis he mole ratio is $B$ between salicylic acid and acetic anhydride in this reaction. 9. Fsing a literature source or the internet, find the accepted melting temperature value of pure acetylsalicylic acid. #ow does the melting temperature test of your aspirin compare to the accepted value '. :ased on the results of the absorbance testing with the Spectrophotometer, what is the percent purity of your sample of aspirin Eoes this percent purity compare well with the results of the melting temperature test 5xplain. 8. Fse your percent purity calculations to determine the percent yield of your synthesis of aspirin.
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Organics Chemistry with Vernier
The Synthesis and Analysis of Aspirin
I)STR$CTOR I)+ORMATIO) $. 5ach lab team will use about 9 g of salicylic acid. 9. he 3.392 "eNO'-' solution can be prepared by using $3.$3 g of "eNO'P O per $ 4. '. he yield for this reaction will be lower than your studentsI expectations. A low yield may not always be the result of sloppy work, but poor lab technique will certainly result in a disappointing yield. 8. (ou may choose to shorten 7art 000 by providing your students with :eerIs law standards. 2. 0t is critical for your students to complete the spectrophotometric analysis of their samples 7art 000- in one lab period, because of the instability of the prepped samples. D. After students complete the 7art $ synthesis, they will need to dry the sample. (ou may choose to have them wait until the next lab period, to ensure that the sample is dry. Or, if you wish to have them complete 7arts 00 and 000 in the same lab period, you will need to provide an air=flow supply low flow- to fairly quickly air dry their aspirin sample.
,A-AR# ALERTS Salicylic acidB #armful if swallowed. 1auses mild skin irritation. 1auses serious eye damage. #0S 1lassificationB #ealth ha*ard−9, "lammability−3, 7hysical ha*ard−3. Acetic anhydrideB Strongly irritating and corrosive. oderate fire risk flash point 8&1-. 1auses severe eye damage. Cear eye protection. #ave access to eyewash. >apors are strongly irritating. Open and dispense in fume hood. Leacts sometimes delayed- violently with water. oderately toxic by ingestion and inhalation. #0S 1lassificationB #ealth ha*ard−', "lammability−9, 7hysical ha*ard−9. 7hosphoric acid o=phosphoric acid-B Skin and eye irritant. oxic by ingestion and inhalation. :urns tissue. #0S 1lassificationB #ealth ha*ard −', "lammability−3, 7hysical ha*ard−3. 5thanolB "ire risk flash point $8.31-. "lammable. Addition of denaturant makes the product poisonous. Store in dedicated flammables cabinet. Skin and eye irritant. oderately toxic by ingestion and inhalation. #0S 1lassificationB #ealth ha*ard−9, "lammability−', 7hysical ha*ard−$. 0ron 000- nitrateB ay intensity fire+ oxidi*er. ay be h armful if swallowed. 1auses skin irritation. ay cause respiratory irritation. #0S 1lassificationB #ealth ha*ard −9, "lammability−3, 7hysical ha*ard−'. he ha*ard information reference is Sigma=Aldrich 1o., $=%33='92='3$3, www.sigmaaldrich.comHsafety=centerHmsds=search.html
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SAMPLE #ATA Part I Synthesis of Aspirin *ass of salicylic acid used (+)
&%$1
,olume of acetic an-ydride used (m")
%$
*ass of acetic an-ydride (1%$' +.m") used (+)
%4$
*ass of aspirin and filter paper (+)
&%&
*ass of filter paper (+)
$%
*ass of aspirin synt-esi/ed (+)
1%
Part II Melting Temperatre #ata *eltin+ temperature ran+e (0C)
13&%133%
Part III Sali!yli! A!id Standard Sto!& Soltion nitial mass of salicylic acid (+)
$%&$1
*oles of salicylic acid (mol)
$%$$14
nitial molarity of salicylic acid (mol.")
$%$$7
Part III Beer's La( #ata for Sali!yli! A!id Standard Soltions Trial
Concentration (mol.")
2!sor!ance
1
%7 5 1$ 4
1%$$
&
4%3 5 1$ 4
$%'3&
3
3%47 5 1$ 4
$%1
4
&%3& 5 1$ 4
$%4&3
1%1 5 1$ 4
$%&11
Test of the Prity of the Synthesi%ed Aspirin
10
nitial mass of aspirin sample (+)
$%4$
2!sor!ance of aspirin sample
$%&77
Concentration of salicylic acid (mol.")
1%$ 5 1$ 4
*oles of salicylic acid in aspirin sample (mol)
1% 5 1$
*ass of salicylic acid in aspirin sample (+)
$%1$
*ass of aspirin in sample (+)
$%3$
Percent aspirin in sample ()
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Organics Chemistry with Vernier
The Synthesis and Analysis of Aspirin
SAMPLE CALC$LATIO)S $. "or the sample data, the theoretical yield of aspirin is 9.D' g. he calculation is based on salicylic acid the limiting reactant-, mol of salicylic acid used Q 9.3$ g R $'%.$' gHmol Q 3.3$8D mol mol of salicylic acid Q mol of aspirin produced theoreticaltheoretical mass of aspirin produced Q 3.3$8D mol $%3.$D gHmol Q 9.D' g 9. he experimentally determined melting temperature of $'9.D1 compares well with the accepted melting temperature of pure acetylsalicylic acid, $'2 1. '. he results of the spectrophotmetric test show that the percent purity of the synthesi*ed aspirin is ?26. his compares reasonably well with the melting temperature test. "or the sample data, the calculations are as follows. he absorbance of the aspirin sample is 3.3%$ . he absorbance of 3.3%$ equals a salicylic acid concentration of $.23 $3 @8 molH4. :ecause the sample volume is $33 m4, the molar amount of salicylic acid impurity in the aspirin sample is $.23 $3 @2 mol. here was $.23 $3 @2 mol of salicylic acid in a 2 m4 sample. his 2 m4 sample was taken from 923 m4 of solution. hus, there is $.23 $3 @2 mol 923H2- Q ?.23 $3 @8 mol of salicylic acid in the initial aspirin sample. he mass of salicylic acid isB ?.23 $3 @8 mol $'%.$' gHmol Q 3.$3 g he initial mass of the aspirin sample is 3.83 g. 0f 3.$3 g of this sample is unreacted salicylic acid, then the percent of aspirin in the sample isB '3 gH83 g- $33 Q ?26. 8. Answers will vary. "or the sample data, the mass of synthesi*ed aspirin is $.&D g. 1orrected for purity, isB $.&D 3.?2- Q $.8? g. he percent yield isB $.8? g R 9.D' g- $33 Q 22.&6.
SAMPLE #ATA
Melting temperature determination for aspirin sample
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Spectrum for salicylic acid with iron (! nitrate
Absorbance vs. concentration for salicylic acid with interpolation
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Organics Chemistry with Vernier
