The aspirin project. Laboratory experiments for introductory chemistry

The Five Senses of Christmas Chemistry. Derek A. Jackson and Andrew P. Dicks. Journal of Chemical Education 2012 89 (10), 1267-1273. Abstract | Full T...
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David B. Brown The University of Vermont Burlington, 05401 and L a w r e n c e B. F r i e d m a n Wellesley College WeIIesIey, Massachusetts 02181

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From t h e s t u d e n t point of view, t h e lahoratory associated with a n introductorv chemistrv course c a n fall anvwhere between a total waste of t i m e a n d t h e most rewarding aspect of t h e course. Generating a n d maintaining interest i n iahoratory work, however, is not a trivial prohcem. A good way t o arouse s t u d e n t interest is t o present "relevant" rather t h a n abstract material, a n d recent experimental outlines i n this Journul (1-n, a n d newer lahoratory m a n u a l s ( 8 - l l ) ,illustrate the move toward relevance i n t h e teaching lahoratory. We have designed a laboratory project which involves t h e synthesis, characterization, a n d study of some reactions of acetylsalicylic acid, a n d t h e comparison of acetylsalicylic acid with t h e major component of various commercial brands of aspirin tablets. T h e project is hoth relevant a n d inexpensive, a n d involves a variety of techniques with minimum equipment. Since t h e work requires several lahoratory periods for completion, i t becomes a small research project, allowing .students t o progress a t their own pace, to feel free to repeat portions when necessary, t o feel a sense of continuity in t h e lahoratory, a n d t o become involved with their lab work, even outside t h e lahoratory. Moreover, t h e project is extremely flexible a n d adaptable: i t c a n r u n for different lengths of time, fit in a t various points during t h e year, have different levels of difficulty, a n d b e a d a p t e d t o different types of students. T h u s far, we have used t h e project a s t h e complete lab i n a one-semester introductory course for nonscience majors, a s a four week project ending t h e first semester of a genera l chemistry course, a n d as a seven week starting project for a general chemistry course. Experimental Details T h e project involves hoth experiments with acetylsalicylic acid, which either has been synthesized or recovered from commercial aspirin samples, a n d experiments using commercial aspirin Samples directly. T h e kxperiments are listed here along with comments o n specific results. Synthesis

of Acetylsalicylic Acid

The compound is prepared by the sulfuric or phosphoric acid catalyzed reaction between salicylic acid and acetic anhydride (10, 12, 13). There is, however, a large spread in the yield and purity of product obtained by individual students.' A brown liquid impurity may appear upon recrystallization from water, usually in trace amounts but sometimes in large quantity, and this impurity may be removed by decanting or filtering the hot aqueous solution. Although a nuisance, the impurity does demonstrate that reactions do not always proceed exactly as expected, and may develor, some sympathy for the problems af commercial manufaeturers. An alternative purification procedure, which consists of dissolving the crude product in a minimum of cold diethyl ether, .followed by addition of hexane until crystallization begins, also has been successful in students'hands. ~~

Laboratory experiments for introductory chemistry

acid also is determined, allowing for a clear distinction between the reactant and product of the synthesis. It also is instructive to determine the melting paint of commercial aspirin samples, since the effect of impurities in the samples on melting points is quite clear. Thus, instead of the 2' range (generally 134-136') observed for the recrystallized acetylsalicylic acid, the aspirin tablets consist of two phases over a rangeZaf about 130-200°C. Approximate solubilities of acetylsalicylic acid in solvents such as water, diethyl ether, benzene, and hexane are determined by mixing weighed amounts of solid with measured volumes of salvent until a saturated solution is obtained. Solubility in a dilute sodium hydrogen carbonate solution also is estimated and eontrasted with solubility in water. Results are in rough agreement with values tabulated in handbooks. The density of acetylsalicylic acid is determined by flotation in mixtures of benzene and carbon tetrachloride. Starting with equal volumes of the two liquids, one or the other is added until the density of the solution is identical to that of the solid, as judged by a lack of preferential movement upon centrifugation. The density of the mixture is then determined pycnometrieally. Most results are in the range 1.30-1.40 g/cmJ, in suitable agreement with the handbook value. As an additional means of characterization, a composite ssmple, made up of small portions of recrystallized material from each student in the class, is analyzed for percent carbon, hydrogen and oxygen. Students determine an empirical formula based upan the results of the elemental analysis. Molecular Weight of Acetylsallcylic Acid The molecular weight of the compound is determined by titration with a standard solution of sodium hydroxide. The titration may be conducted in water, but because of limited solubility in water, the titration also has been performed in mixtures of ethanol and water, using in bath cases phenolphthalein as indicator (14, 15). The results tend to he somewhat variable, hut generally are within about 10 mass units of the correct value of 180 g/male. The titration also can be conducted with a pH meter, adding a different view to students' concept of pH, end-points, and acidbase equilibria, and allowing for a determination of Ka for acetylsalicylic acid. Conversion

of Acetylsalicylic Acid fo Salicylic Acid

Acetylsalicylic acid is hydrolyzed to sodium salicylate by hailing an aqueous solution of the former compound which has been made strongly basic by the addition of sodium hydroxide. The cooled solution is neutralized with sulfuric aeid, made slightly acidic, then extracted with several portions of diethyl ether. The ether solution is evaporated to dryness and the crude salicylic acid is recrystallized from water. The physical properties (melting point, solubility, density, etc.) of the salicylic acid obtained in this way may be compared with those of the salicylic aeid used in the synthesis described above. Spectroscopic Properties of Acetylsalicylic Acid

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Characterization of Acetylsalicylic Acid The melring pmnr of scerylialiqlic acid is derermmcd usmg rhc usual lal~lraturvprocedure and the rnrlting pomt of jalwyla 214

The Aspirin Project

/ Journalof Chemical Education

The ultraviolet spectrum of a chloroform solution of acetylsali-

'A reviewer has suggested that excess sulfuric acid greatly decreases the yield of acetylsalicylic acid. 2 A reviewer has painted out that hydration of acetylsalicylic acid often is extensive, thus the melting point is not a good criterion of purity for the compound.

cyclic acid shows a single strong absorption maximum at 277 mfl, in agreement with the literature value (16). The ' H nuclear magnetic resonance spectrum (in CDCld consists of a sharp singlet at 2.3 ppm downfield from the TMS signal, and a complex group of peaks between 7 and 8.2 ppm, as reported earlier (17). The positions of these two regions of absorption, together with the area ratios of 3:4, allow assignment of the upfield signal to the methyl hydrogen atoms, and the downfield signal to the aromatic hydrogen atoms. The hydroxy hydrogen resonates at 10.8 ppm downfield from TMS (17). The infrared spectrum, easily obtained in a KBr matrix, is particularly rich in absorptions ( l a ) , and serves as an excellent spectroscopic fmgerprint. Characterization of Commercial Aspirin as the Acid Althuugh m'st sources claim that aspirin is acr~yl~nlir?lic ac~d. other? suggest ir is thr salt sodrum acetylsalirylate (19 231. The presence of \'a' in aspirill rnhlrtr can easil) he rherwd hy a flame test and/or precipitating sodium zinc uranyl acetate. In agreement with the Merck Index and the U. S. Pharmacapeia, all eommercial aspirin tablets tested were found to be free of sodium. Recovery of Acetylsalicylic Acid hom Aspirin Tablets Acetylsalicylic acid may be recovered from aspirin tablets in several ways. Plain aspirin tablets, which contain from 10% to 20% starch binder, are crushed and mixed with warm ethanol, and the binder is removed by filtration. Evaporation of the ethanol solution yields a residue which is recrystallized from water. providing a high yield of well-formed crystals. Attempts to condense this procedure into one step were generally unsuccessful, because of mechanical difficulties in the filtration process. Alternatively, the crushed tablets are mixed with diethyl ether, the mixture is filtered to remove binder, and hexane is added to the ether solution until crystallization begins. Tablets which contain phenacetin and/or caffeine in addition to acetylsalicylic acid and starch provide a mare challenging separation problem (2). An extraction with excess cold ether separates the very soluble acetylsalicylic acid and moderately soluble phenacetin from the insoluble caffeine and starch. Treatment of the insoluble fraction with benzene or ethanol allows for a separation of the caffeine. ~,soluble in both of these solvents. from the srarch. The aubrranrinl rlXerenut in ether .;oltlhility should alluw for a suitablr separation uf acetyl~alirylicneid and phenacetin. hut in practwe thissepararton has proved d:fficdr. ~

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Percent Acetylsa~icylicAcid in Aspirin Tablets All of the aspirin tablets studied come in bottles which indicate that each tablet contains "5 grains U.S.P. aspirin." Several tablets of each brand are weighed and an average weight per tablet is determined. The difference between the average weight per tablet and 5 grains is assumed to be due to "inert ingredients" (presumably the binder), and the percent acetylsalicylic acid per tablet is calculated. A mare accurate percentage for acetylsalicylic acid is obtained by titrating a sample of aspirin tablets with aqueous sodium hydroxide using one of the procedures described above. The results of these studies suggest that aspirin tablets contain from 75% to 90% acetylsalicylic acid, in agreement with earlier studies reported in this Journal (14, 15). Additional Experiments In addition to the experiments described above, other experiments have been incorporated into the aspirin project. Both the starch binder, common in all commercial aspirin tablets, and caffeine, which is found in certain acetylsalicylic acid-containing analgesic preparations, have been isolated by students in sufficient purity to allow for characterization by study of physical and spectroscopic properties. A few students have successfully separated' and identified components using a recently reported thin-layer chromatographic procedure (2). Finally, a small number of students have extended th2ir studies to "buffered" and "extrastrength" commercial samples. Application of the Project The aspirin project has been used for two years as the complete laboratory accompanying a one-semester introductory course in contemporary problems in chemistry designed for nonscience majors a t Wellesley College. The average course enrollment has been 46, and the class has

been sectiofied into laboratory groups of 16-20 students, each group meeting for one 3% hour period per week over a 13-week term. Students work individually a t their own pace, are expected to complete certain designated experiments with acetylsalicylic acid, a n d are encouraged to complete a s many additional experiments with acetylsalicylic acid and aspirin tablets as their time and interest allow. However, emphasis is placed upon t h e quality rather than the quantity of the work done. Although a few students have opted t o do the minimum number of experiments, most have pursued their laboratory work with enthusiasm, and many have done a n exceptional job, completing most of the experiments outlined above a t a very high level. T h e overall student response t o the laboratory work has been excellent. The project has been used a s the laboratory work for the last four weeks of the first semester in a large (200 students) general chemistry course a t the University of Vermont. By this point in the semester students have enough laboratory experience t o enable them t o work efficiently, and consequently to do many of the experiments described above in a short period of time. Their results were generally good, and, more important, their attitude was very good. Upon completion of the semester more t h a n half of them evaluated the aspirin project a s "excellent," and many commented t h a t for the first time they had become interested in chemistry and felt t h a t it might be able to say something which related t o them directly. T h e project also has been used as a n introductory laboratory experience for a group of 40 students from a general chemibtry course (University of Vermont). An attempt was made t o remove all "cook-book" aspects of the lab, and create a n open-ended research approach. In essence, each student was provided with a bottle of aspirin tablets, given suggestions about possible studies to conduct, and directed to the library. The results of this approach were somewhat mixed. with the instructor. the teachine assistants, and the students being initially totally fru&ated, b u t ultimatelv achieving a sense of considerable satisfaction. In the first three weeks of this experience less was accomplished than would have been in two hours of work following detailed instructions. However, in the following four weeks students probahly accomplished a s much, totally on their own, a s they would have if given detailed instructions. Literature Cited (11 Frank. F.. Roberts. T., S n d , J., Yster. C.. and Collier J.. J. CHEM. EDUC.. 46. 255i19111. Lieu, V.T..J. CHEM.EDUC.. 46.47Si19711. Kriz, G.S., Jr., a n d f i i z , K.D.. J. CHEM.EDUC.. 48.551 (19711. Hahrahsn,E. S.. J . CHEM.EDUC.. 46.511 (19691. Mohrig. J . R . . J . CHEM. EDUC., 49. lSi1972). McFsrland, J. H.andBenton, C.S.. J. CHEM. EDUC.. 49.21 (19721. Suplinkas. R. J.. J. CHEM. EDUC., 49.24 (19721. Franfr. H. W.. and Maim, L. E.. Editors. "Laboratory separates in Chemistry. LWl-1082." Val. 1, W. H. Fleeman and Company. San Francisco, 1970, numbers 1W6, 1049. (9) Birdwhistell, R. K.. and monnor, R.. Editor& ''Laboratory separate8 in Chomlsf ~ 108-1122." . Vol. 2. W. H. Freeman and Company. San Francisco, 1971. n & k r 1116. 1101 Smith, W. T..and Wmd. J. H.. " L a b o r a m Manual for College Chemistry,"4fh od., Harper and Rau. New York. 1971. p a w 195-202. (111 Sacks, L. J.. "Experimental Chemistry," Tho MaeMillan Company, New Ymk, 1971,pagps lS6191. 1121 Robertson, G. R., "Laboratow PIactice of Organic Chemistry." The MseMillan Company, New York. 1943. p. 323. 1131 Fieoer. L. F.. "Organic Experimenta." D. C. Heath and Company. New York. ,*C" -,?. " 9*c 114) Shm, S.Y.,andGilman,A. J., J. CHEM. EDUC., 42.S40i19651. (15) Vinson,J.A.,andHaker, E. K.. J.CHEM. EDUC.. 46.245 119691. (161 Jonas. M., andThatchcr.R.L.. A m l . C h m . 23.957i19511. (17) Hollk. D.P.. Anal. Cham.. 35.1682i19631. (181 Parke, T. V.. Ribloy. A . M . , Kennedy, E. E., and Hilty, W. W., Anal. C h m . . 23. 953 (19511. (191 Hendriekon. J. B.. Cram. D . J.. and Hammond, G. S.. "Organic Chemistry," McGraw-Hill.NowYork. 1970,p. 134. (20) Roberts. J. D.. and C e r i o . M. C.. "Basic Principles of O~gsnicChemistry." W. A. Benjamin, No- York. 1965.p. 953. 1211 . . Fipser. L. F.. and Fiser. M.. "Advanced Oceanic Chemiatw." Reinhold. New ~ m k 1961.r). . 799. 1221 Morrison. R. T., and Boyd. R. N.. "Organic Chemistry." Allyn and Bseon, Boston. 1966, p. 809; 1959.p. 603. in) collier, H. O. J.. "~spirin."sci ~ m . ZW. . NO.5.96 119681. (21 131 (4) (51 (61 (7) (81

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