Organic Chemistry with Vernier Vernier Software & Technology 1

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 two primary ob)ectives in this experiment will be to synthesi*e and analy*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 acid ,which acts as a catalyst-. he reaction
equation is shown below.
C H
3
O CH
3
O O
C H
3
OH
O
+
+
O O H
O
CH
3
O
O O H
OH
H
3
P O
4
( a q )

Salicylic acid Acetic anhydride Acetylsalicylic acid Acetic acid

(ou will conduct two tests of your synthesis to verify that you did indeed make aspirin, and to
determine its relative 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.
2 Organics Chemistry with Vernier
MATERIALS
Part I Synthesis Materials
23 m4 5rlenmeyer flask solid salicylic acid
two $3 m4 graduated cylinders %26 phosphoric acid solution, #'7O8
92 m4 graduated cylinder liquid acetic anhydride
923 m4 beaker distilled water
:;chner funnel, filter, and filter paper cold distilled water
spoon, spatula, or rubber policeman balance
ice bath emperature 7robe or thermometer
hot plate watch glass
plastic :eral pipet or eyedropper
Part II Melting Temperatre
4ab<uest or computer interface aspirin crystals ,from 7art 0-
4ab<uest App or 4ogger Pro tissues ,preferably lint=free-
>ernier .elt Station mortar and pestle ,optional-
glass capillary tubes, one end closed
Part III Spe!trophotometri! A"sor"an!e
4ab<uest or computer interface salicylic acid
4ab<uest App or 4ogger Pro aspirin crystals ,from 7art 0-
Spectro>is 7lus spectrophotometer ethanol, denatured
23 m4 graduated cylinder 3.392 . iron ,000- nitrate solution, "e,NO'-'
plastic cuvette with lid distilled water
923 m4 beaker $33 m4 volumetric flask
$33 m4 beaker 923 m4 volumetric flask
PROCE#$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@%3A1 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
$3 minutes into the heating.
Organic Chemistry with Vernier 3
The Synthesis and Analysis of Aspirin
2. Next you will crystalli*e the aspirinB
a. Chen you are confident that the reaction has reached completion ,no vapors appearing-,
carefully remove the flask from the hot plate and add 93 m4 of distilled water.
b. Allow the mixture to cool to near room temperature. ransfer the flask to an ice bath for
about five minutes. As the mixture cools, crystals of aspirin should form in the flask.
D. Now you will wash the synthesi*ed aspirinB
a. Set up a vacuum filtration using a :;chner funnel. :e sure to weigh and record the mass
of the filter paper to the nearest 3.3$ 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 $2 seconds, turn the suction back on. Cash the crystals with cold, distilled
water twice more in this manner.
e. !ently transfer the filter paper with your product onto the watch glass to air dry. As
directed by your instructor, either direct a gentle stream of air ,low flow- to help dry the
solid, or let them air dry until the next lab period.
f. Ceigh the dried recrystalli*ed product on the filter paper and record the mass to 3.3$ 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<uest or to a computer interface.
$$. Start the data=collection program, then choose New from the "ile menu. (ou are now set up
to take melting temperature data for up to 93 minutes.
$9. 0n the first trial, you will want to observe the melting process and make a rough estimate of
the melting temperature of your aspirin sample. EonIt worry if the heating rate is a bit too
rapid and the sample melts too quickly. o do thisB
a. Start data collection.
b. On the .elt Station, turn the control knob to a setting of 993J1. he red light will turn on
indicating active heating.
4 Organics Chemistry with Vernier
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<uest-. Chen the entire solid has completely melted, click .ark again. he two
values marked on your graph describe the estimated melting temperature range of your
substance.
d. Chen you have determined the approximate melting temperature range for the sample,
stop data collection. Store the run by tapping the "ile 1abinet icon in 4ab<uest, or
choosing Store 4atest Lun from the 5xperiment menu in 4ogger Pro. Eiscard the
capillary tube and sample as directed by your instructor.
e. On the .elt Station, turn the control knob to the "anH1ooling setting to get ready for the
next trial. he blue light will turn on indicating that the fan is cooling the .elt Station.
$'. Now that you have a rough idea of the melting temperature, a more accurate determination of
the melting temperature can be made. Fse a previously prepared sample in a capillary tube,
as described in Step %, to determine the melting temperature of the sampleB
a. Start data collection.
b. On the .elt Station, turn the control knob to the Lapid #eat setting.
c. 1arefully observe the temperature vs. time graph. Chen the temperature is within
approximately $3J1 of the lowest possible melting temperature of your sample, turn the
control knob to a temperature setting corresponding to your expected melting temperature.
d. 1arefully observe your sample. Chen the solid begins to melt, click .ark to mark the
temperature on your graph. Chen the entire solid has completely melted, click .ark
again. he two values marked on your graph describe the estimated melting temperature
range of your substance. Chen you are finished with this step, stop data collection.
e. Store the run.
f. Eiscard the capillary tube and sample as directed by your instructor.
g. On the .elt Station, turn the control knob to the "anH1ooling setting to get ready for the
next trial.
$8. Lepeat Step $' until you have determined the melting temperature range of your aspirin.
Lecord the melting temperature range in your data table.
$2. At the end of your testing, turn the control knob on the .elt Station to Off.
Part III Test the Spe!trophotometri! A"sor"an!e of an Aspirin Sample
(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. <uantitatively prepare the stock salicylic acid solution.
a. .easure out about 3.93 g of salicylic acid. Lecord the mass, to the nearest 3.33$ g.
b. ransfer the salicylic acid to a 923 m4 beaker and add $3 m4 of ethanol. Swirl the beaker
to dissolve the solid.
c. Add $23 m4 of distilled water to the beaker. .ix the solution.
Organic Chemistry with Vernier 5
The Synthesis and Analysis of Aspirin
d. <uantitatively transfer the solution from the beaker to a 923 m4 volumetric flask.
horoughly rinse the beaker with several portions of distilled water, and transfer the rinse
water to the volumetric flask. Add distilled water, as needed, to fill the flask to the 923 m4
mark. .ix the solution thoroughly. 1alculate the precise molar concentration of your
stock solution and record it in your data table.
$?. 7repare five standard solutions of varying concentrations of salicylic acid.
a. o prepare $33.3 m4 of your standard solution ,the solution you will use for rial $-,
quantitatively transfer $3.3 m4 of the stock salicylic acid solution you prepared in Step $D
to a $33 m4 volumetric flask.
b. Add 3.392 . "e,NO'-' solution to the flask to make precisely $33 m4.
a. 7repare the remaining four salicylic acid standard solutions according to the table below,
diluting the standard solution in the $33 m4 flask with distilled water. .ix thoroughly.
b. 1alculate the precise molar concentrations of the five standard solutions in the table above
and record them in your data table.
Trial
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<uest
or a computer. Start the data=collection program, then choose New from the "ile menu.
$&. 1alibrate the Spectrophotometer.
a. o prepare a blank cuvette, fill a cuvette 'H8 full with 3.392 . "e,NO'-' solution. 7lace
the blank cuvette in the Spectrophotometer.
b. 1hoose 1alibrate from the Sensors menu of 4ab<uest or the 5xperiment menu of
4ogger Pro.
c. Chen the warmup period is complete, select "inish 1alibration. Select OK.
93. Eetermine the optimal wavelength for creating the standard curve and set up the mode of
data collection.
a. 5mpty the "e,NO'-' solution from the blank cuvette. Fsing the solution in the $33 m4
volumetric flask of salicylic acid ,rial $-, rinse the cuvette twice with G$ m4 amounts,
and then fill it 'H8 full. Cipe the outside with a tissue and place it in the
Spectrophotometer.
b. Start data collection. A full spectrum graph of the solution will be displayed. Stop data
collection. he wavelength of maximum absorbance , max- is automatically identified.
6 Organics Chemistry with Vernier
c. 1hange the mode to 5vents with 5ntry ,absorbance vs. concentration- and select a
wavelength for analysisB
0n 4ab<uest App, the displayed wavelength of maximum absorbance , max- is
automatically identified on your graph with a point protector. ap the .eter tab, then tap .ode.
1hange the mode to 5vents with 5ntry. 5nter the Name ,1oncentration- and Fnits ,molH4-.
Select OK.
0n 4ogger Pro, click the 1onfigure Spectrometer button, . 1lick Abs vs. 1oncentration
as the 1ollection .ode. he wavelength of maximum absorbance , max- will be selected.
9$. (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 concentration 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. <uantitatively transfer the solution from the beaker to a 923 m4 volumetric flask.
horoughly rinse the beaker with several portions of distilled water, and transfer the rinse
water to the volumetric flask. Add distilled water, as needed, to fill the flask to the 923 m4
mark. .ix the solution thoroughly.
e. ransfer 2 m4 of the aspirin solution from the 923 m4 volumetric flask to a clean and dry
$33 m4 volumetric flask. Add 3.392 . "e,NO'-' solution to the flask to make precisely
$33.3 m4. .ix the solution thoroughly.
Organic Chemistry with Vernier 7
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<uest-. 0f the absorbance value falls within the range of the salicylic acid standard
solutions, record it in your data table. Note: 0f the absorbance value does not fall within
the range of the salicylic acid standard solutions in your data table, you can repeat
Step 99e using a more dilute or more concentrated solution.
98. o determine the concentration of the salicylic acid impurity in the treated aspirin sample,
interpolate along the regression line to convert the absorbance value of the unknown to
concentration.
a. 1hoose 0nterpolate from the Analy*e menu.
b. 1lick or tap any point along the regression curve ,or use the M or N keys on 4ab<uest-
to find the absorbance value that is closest to the absorbance reading you obtained in
Step 9'. he corresponding salicylic acid concentration, in molH4, will be displayed to the
right of the 4ab<uest graph, or on your 4ogger Pro graph.
c. Lecord the concentration of salicylic acid in your data table.
92. Eiscard all solutions as directed.
#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
1nitial mass of salicylic acid (+)
*oles of salicylic acid (mol)
1nitial molarity of salicylic acid (mol.")
8 Organics Chemistry with Vernier
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
1nitial 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 (3)
#ATA A)AL*SIS
$. Chat is the theoretical yield of aspirin in your synthesisO 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 valueO
'. :ased on the results of the absorbance testing with the Spectrophotometer, what is the
percent purity of your sample of aspirinO Eoes this percent purity compare well with the
results of the melting temperature testO 5xplain.
8. Fse your percent purity calculations to determine the percent yield of your synthesis of
aspirin.
Organic Chemistry with Vernier 9
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 . "e,NO'-' solution can be prepared by using $3.$3 g of "eNO'P&#9O 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*ard9, "lammability3, 7hysical ha*ard3.
Acetic anhydrideB Strongly irritating and corrosive. .oderate fire risk ,flash point 8&A1-.
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', "lammability9, 7hysical ha*ard9.
7hosphoric acid ,o=phosphoric acid-B Skin and eye irritant. oxic by ingestion and inhalation.
:urns tissue. #.0S 1lassificationB #ealth ha*ard', "lammability3, 7hysical ha*ard3.
5thanolB "ire risk ,flash point $8.3A1-. "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*ard9, "lammability', 7hysical
ha*ard$.
0ron ,000- nitrateB .ay intensity fire+ oxidi*er. .ay be harmful if swallowed. 1auses skin
irritation. .ay cause respiratory irritation. #.0S 1lassificationB #ealth ha*ard9,
"lammability3, 7hysical ha*ard'.
he ha*ard information reference is Sigma=Aldrich 1o., $=%33='92='3$3,
www.sigmaaldrich.comHsafety=centerHmsds=search.html
10 Organics Chemistry with Vernier
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%4(
Part II Melting Temperatre #ata
*eltin+ temperature ran+e (0C) 13&%(133%4
Part III Sali!yli! A!id Standard Sto!& Soltion
1nitial mass of salicylic acid (+) $%&$1
*oles of salicylic acid (mol) $%$$14)
1nitial molarity of salicylic acid (mol.") $%$$)74
Part III Beer's La( #ata for Sali!yli! A!id Standard Soltions
Trial Concentration (mol.") 2!sor!ance
1 )%74 5 1$
4
1%$$)
& 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
1nitial 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 (3) 7)
Organic Chemistry with Vernier 11
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 ,theoretical-
theoretical mass of aspirin produced Q 3.3$8D mol S $%3.$D gHmol Q 9.D' g
9. he experimentally determined melting temperature of $'9.DA1 compares well with the
accepted melting temperature of pure acetylsalicylic acid, $'2A1.
'. he results of the spectrophotmetric test show that the percent purity of the synthesi*ed
aspirin is ?26. his compares reasonably well with the melting temperature test.
"or the sample data, the calculations are as follows.
he absorbance of the aspirin sample is 3.3%$. he absorbance of 3.3%$ equals a salicylic
acid concentration of $.23 S $3
@8
molH4. :ecause the sample volume is $33 m4, the molar
amount of salicylic acid impurity in the aspirin sample is $.23 S $3
@2
mol.
here was $.23 S $3
@2
mol of salicylic acid in a 2 m4 sample. his 2 m4 sample was taken
from 923 m4 of solution. hus, there is ,$.23 S $3
@2
mol S ,923H2- Q ?.23 S $3
@8
mol of
salicylic acid in the initial aspirin sample. he mass of salicylic acid isB
?.23 S $3
@8
mol S $'%.$' 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- S $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 S 3.?2- Q $.8? g. he percent yield isB ,$.8? g R 9.D' g- S $33 Q 22.&6.
SAMPLE #ATA
Melting temperature determination for aspirin sample
12 Organics Chemistry with Vernier
Spectrum for salicylic acid with iron (! nitrate
Absorbance vs. concentration for salicylic acid with interpolation