Experiment 11

Chemicals & Equipment Bunsen burner or hot plate Boiling stones Buchner funnel 5 !m" filter flas# filter paper '5 !m" flas# * bea#er melting point apparatus Time: ,art - * ,art -- .3 hours/

Synthesis and Analysis of Aspirin

salicylic acid commercial aspirin 1% FeCl3 acetic anhydride 1$% &'S() +5% ethanol capillary tubes

-ntroduction
Aspirin is most 0idely sold o1er!the!counter drug2 -t has the ability to reduce fe1er .an antipyretic/3 to reduce pain .an analgesic/3 and to reduce s0elling3 soreness3 and redness .an anti!inflammatory agent/2 (ne of the first recorded accounts for the disco1ery of aspirin appeared in England3 in 14533 crediting the bar# of 0illo0 trees 0ith a beneficial effect in alle1iating distress due to fe1ers3 aches3 and pains2 "ater3 the compound salicylic acid .named for the "atin 0ord for 0illo03 salix/ 0as isolated from 0illo0 bar#6 it pro1ed to be the acti1e ingredient2 By 1$5 3 organic chemists 0ere able to synthesi7e salicylic acid from basic starting materials3 this furthered the therapeutic use of the substance3 but there 0ere problems2 Salicylic acid pro1ed to be irritating to the membranes of the throat3 mouth3 and stomach2 8hese problems are directly associated 0ith the high acidity of the compound3 but a simple remedy 0as disco1ered3 namely3 replacement of the acidic phenolic hydrogen atom 0ith an acetyl group2 9hen interpreting the structures of the abo1e organic compounds3 note the follo0ing characteristics of these molecules2 (rganic molecules are complex compounds of carbon2 Carbon al0ays bonds to four other groups or atoms2 9hen outline structures .condensed/ are gi1en3 such as the hexagon3 each point of the hexagon represents a carbon atom2 -f a double bond3 :3 is present and the carbons are attached in a ring3 only one hydrogen is attached to gi1e the full compliment of four bonds2 -f a triple bond is present then only one other atom may be attached2 Chec# the structures belo0 to see that each carbon has four and only four bonds2 ;itrogen3 on the other hand3 0ill bond co1alently to only three atoms3 and then oxygen bonds only to t0o2 A useful synthesis of acetylsalicylic acid 0as de1eloped in 1$+33 patented in 1$++3 mar#eted under the trade name of <aspirin= by the Bayer Company in >ermany2 8he name aspirin 0as in1ented by the chemist3 Felix &ofmann3 0ho originally synthesi7ed acetylsalicylic acid for Bayer2 %ore than 5 million 5!grain tablets of aspirin are consumed daily in

the ?nited States2 -n ,art - of this experiment3 you 0ill prepare aspirin by reaction of salicylic acid 0ith acetic anhydride3 using concentrated sulfuric acid as a catalyst2 By doing so you 0ill learn some preparati1e procedures used in organic synthesis in general2 Aspirin still has its side effects3 note that the carboxylic acid functional group remains intact2 8his may result in hemorrhaging of the stomach 0alls e1en 0ith normal dosages2 8he acidic irritation can be reduced through the use of buffering agents3 li#e antacids3 in the form of magnesium hydroxide3 magnesium carbonate3 and aluminum glycinate 0hen mixed 0ith aspirin .Bufferin/2 9hile the ester can be formed from acetic acid and salicylic acid3 a better preparati1e method uses acetic anhydrides in the reaction instead of acetic acid2 An acid catalyst3 li#e sulfuric acid or phosphoric acid3 is used to speed up the process2 -n ,art -- of this experiment you 0ill measure the percent acidity of aspirin by titration 0ith a strong base2

Part I Synthesis of Aspirin Caution@ 8he preparation of aspirin in1ol1es the use of t0o ha7ardous materials ! concentrated sulfuric acid and acetic anhydride2 ,roceed only if you ha1e a fume hood to 0or# in3 and after you ha1e listened carefully to the instructorAs safety directions2 Procedure
12 9eigh )2 g . 2 3 mole/ of salicylic acid in a 1'5 m" Erlenmeyer flas#2 ?sing this Buantity of salicylic acid to calculate the theoretical yield of aspirin2 Cecord the 0eigh on the report sheet2 '2 Carefully add 5 m" . 2 51 mole/ of acetic anhydride to the flas#2 .Care! Acetic anhydride is irritating to the s#in and eyes2/ 32 Using e treme caution3 add 5 drops of concentrated sulfuric acid to the flas#3 s0irl gently3 and place the flas# in a bea#er of boiling 0ater2 Clamp the flas# to a ring stand and heat for ' minutes2 Constantly stir 0ith a glass rod6 the entire solid must completely dissol1e2 )2 Cemo1e the flas# from the boiling 0ater bath and allo0 to cool to room temperature2 Crystalli7ation should occur during cooling2 -f crystals begin to gro03 let the flas# sit undisturbed until crystals stop gro0ing then add the ) m" of ice 0ater2 -f crystals do not gro03 slo0ly pour the solution into a '5 !m" bea#er containing ) m" of ice 0ater3 mix thoroughly3 and place the bea#er in ice 0ater and let sit undisturbed until crystals ha1e gro0n2 8he 0ater destroys any unreacted acetic anhydride and 0ill cause the insoluble aspirin to precipitate out of solution2 52 Collect the crystals by 1acuum filtration2 52 9ash the crystals 0ith t0o 1 !m" portions of cold 0ater follo0ed by one 1 ! m" portion of cold ethanol2 Allo0 the crude product to dry3 then 0eigh it on the rough balance2 42 9eigh a 0atch glass2 Add the crystals and re!0eigh2 Calculate the 0eight of crude aspirin2 Determine the percent yield2 8est a small amount of this crude product for its melting point as described in ,art --2 8est the freshly made product for purity2 Aspirin naturally decomposes into acetic acid o1er time so the purity test should be done the day the aspirin is prepared2 Sa1e some of your aspirin for testing2 !ecrystalli"ation The crude aspirin needs to be further purified. The crude products obtained from most preparations of organic compounds are contaminated with unreacted starting materials and substances from side-reactions. These can often be eliminated by a simple process known as RECRYSTAl !"AT!#$. The ne%t phase of this e%periment in&ol&es the recrystalli'ation( and thus( purification( of your crude aspirin sample. $2 Dissol1e about '!) g of your crude product in about ' m" ethyl alcohol in a 1'5 m" Erlenmeyer flas#3 0arming the alcohol in a 0ater bath to effect dissolution2 Caution: #o not use a flame to heat ethyl alcohol$ As it is a flamma%le compound$ -f you obtained less than 5 g of crude product3 use proportionately less alcohol2 +2 -f any solid material remains undissol1ed3 filter the solution2 1 2 Add 5 m" of 0arm 0ater .about 5 oC/ to the clear alcohol solution2 -f any crystals appear at this point3 heat the contents of the flas# until they dissol1e2 112 Set the flas# aside to cool3 obser1ing it carefully2 1'2 9hen crystals start to form3 cool the flas# by surrounding it 0ith cold 0ater2 8he crystalli7ation process 0ill then go to completion2 132 Collect the crystals by 1acuum filtration2 1)2 Allo0 the crystals to dry2 152 Sa1e your sample of the aspirin for a melting point determination and further analysis2
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Part II A&A'(SIS )* ASPI!I& A$ #etermination of the +elting Point

%ost organic compounds ha1e a sharp melting point3 0hich can be measured accurately to 0ithin 1oC or better3 using the method belo02 Furthermore3 the measurement is easily made 0ith a small Buantity of material .a fe0 small crystals/ using a simple apparatus2 %elting point determinations are routinely made on solid organic compounds3 and extensi1e compilations of melting points are a1ailable in reference boo#s2 (ne use of the melting point is to establish that a preparati1e or isolation procedure has led to an expected product2 .8he prepared substance should ha1e the documented melting point for that substance2/ A 1ery pure substance has a 1ery sharp melting point2 Further purification 0ill not change the melting point2 "ess pure substances melt o1er a range of temperatures that is belo0 the actual melting point of pure material2 8hus the sharpness of a melting point is a useful criterion of purity2 9hen a melting point is determined3 it is therefore important that the melting range be recorded2 8he bottom of the melting range is the temperature at 0hich the first signs of liBuid can be seen2 8he top of the melting range is the temperature at 0hich the last of the solid fuses3 i2e2 turns into liBuid2 8he compound is generally regarded as pure enough for most purposes if the melting range is no greater than 'oC2 A 0ide melting range signals the need for further purification2

Procedure
12 '2 (btain a capillary tube from your instructor3 and gently press the open end into the pile of aspirin crystals on the paper so that a fe, crystals of aspirin enter the capillary tube2 8ap the closed end of the capillary onto the bench top3 so that the aspirin crystals 0or# their 0ay to the bottom2 8he aspirin crystals should be firmly pac#ed3 and fill the capillary tube to a depth of no more than 1!' mm2 -nsert the capillary tube containing the sample into the melting point apparatus2 Cecord the temperature 0here the melting point is first obser1ed and 0hen it becomes a liBuid completely2 8his is your melting point range2 %elting point of purified aspirin is 135!135 oC2

-$ #etermination of Purity
,henols form a colored complex 0ith the ferric ion2 -f phenol is present in a sample3 the resulting color means the product is impure2 8he purple color indicates the presence of a phenol group2 8he intensity of the color Bualitati1ely tells ho0 much impurity is present2

Procedure
12 '2 32 "abel three test tubes6 place a fe0 crystals of salicylic acid into test tube E13 a small sample of your aspirin into test tube E'3 and a small sample of crushed commercial aspirin into E32 Add 5 m" of deioni7ed 0ater to each test tube and s0irl to dissol1e the crystals2 Add 1 drops of 1% ferric chloride to each test tube2 Compare and record your obser1ations2

Chemistry 51 Report Sheet - Aspirin ..Experiment

Part I

NAME: 1. Theoretical yield: __________g (1 mol / 138 g salicylic acid) (180 g/ 1 mol) = _________________g of aspirin
Mass of salicylic acid Theoretical yield of aspirin

. Experimental yield: Weight of aspirin & atchglass Weight of atch glass Mass of cr!de prod!ct o"tained after s!ction filtration #ercent $ield of cr!de prod!ct (e%pt / theo & 100) Mass of re(crystalli)ed prod!ct (optional) #ercent $ield of re(crystalli)ed prod!ct (e%pt / theo & 100)

________________g ________________g ________________g ________________' ________________g ________________' (*nd trial)_______ (*nd trial)_______

Part II
Melting #oint of cr!de prod!ct Melting #oint of re(crystalli)ed prod!ct +erric ,hloride Test (#!rity test) -.M#/0 ,1/12 34T04-3T$ (1st trial)______ (1st trial)______

-alicylic acid $o!r aspirin ,ommercial aspirin

!"EST#$NS: 15 What is the p!rpose of the 18M s!lf!ric acid in the preparation of aspirin6 *5 0%plain hy the percent of yo!r aspirin as different from the res!lts o"tained from the commercial aspirin5 35 1ld aspirin e%posed to moist!re often smells li7e acetic acid (8inegar)5 When aspirin is heated in "oiling ater9 it decomposes and gi8es off a 8inegar smell5 The res!lting sol!tion gi8es a positi8e +e,l3 test5 Why is this test positi8e6 Write the chemical e:!ation for the reaction of aspirin and ater at high temperat!res5 ;5 $o! ha8e spent a"o!t 1< ee7s learning a"o!t chemistry and its respecti8e la"oratory techni:!es5 The typical street(dr!g prod!cer !s!ally doesn=t ha8e any chemistry "ac7gro!nd "!t instead simply mimics the synthesis learned from another person or9 in some cases9 a "oo75 3f yo! ta7e this into consideration along ith yo!r s!ccess at prod!cing aspirin9 ho ell do yo! tr!st the prod!cers of street dr!gs to ma7e dr!gs safe for cons!mer !se6
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