Recrystallization of Acetanilide Authors: ABESAMIS, M.F., ACOSTA, M.C., AGUSTIN, F., AQUITANIA, M.C., M.C., BAGSICAN, M.J. Abstract Recrystalliz Recrystallization ation is a common method of purifying purifying organic substances thro throug ugh h the the diff differ eren ence ce in solu solubi bili lity ty at diff differ eren entt temp temper erat atur ure. e. In this this experiment, acetanilide was produced by acetylation of aniline with acetic anhydr anhydride ide.. The crude crude acetan acetanilid ilide e was was dissol dissolved ved in a solvent solvent in a heatin heating g water bath. The solution was cooled slowly in an ice bath as crystals form out. As the compou compound nd crysta crystalliz llizes es from from the sol soluti ution, on, molecu molecules les of other other compounds dissolved in solution are excluded from growing crystal lattice, yielding pure acetanilide. I. Intr Intro oduct ductio ion n Organi Organic c compou compounds nds that that are solid solid at roo room m temper temperatu ature re are usually usually purified purified by crystallizat crystallization. ion. Crystallization Crystallization is the deposition of crystals crystals from a solut sol utio ion. n. Duri During ng the the proc process ess of crys crysta tall form format ation ion,, a molec molecul ule e have have the the tendency to be attached to a growing crystal composed with the same same type of molecules because of a better fit in a crystal lattice of a molecule of the same structure than for other molecule. (Pastro, John, & Miller) Lattice is a fixed fixed and rigid rigid arrang arrangeme ement nt of ato atoms, ms, molecu molecules les or ions. ions. (Mullin (Mullin,, 1961) 1961) Recrys Recrystal talliz lizati ation on is a method method in which which two crysta crystalliz llizati ation on proces processes ses was was performed. It is referred to the second crystallization. (Pavia, Lampman, Kriz, Kriz, & Engel, 1999) It depends on the difference difference of solubility solubility of a substance in a hot and in a cold solvent. Solubility is the degree of substance which is the solute to be dissolved in solvent. It is the main factor that affects crystallization. Before performing cryst crystal alli liza zatio tion, n, ident identif ifyin ying g a recr recrys ystal talli lizi zing ng sol solve vent nt is signi signific fican ant. t. The The substa substance nce to be crysta crystalliz llized ed should should show the ideal ideal solubil solubility ity behavi behavior or in solvent. A substance can be purified when both the desired substance and the impurity have similar solubility at its boiling point temperature, and when the impuri impurity ty repres represent ents s only only a small small fract fraction ion of total total solid. solid. The desire desired d substa substance nce will will crysta crystalli llize ze on coo cooling ling,, but the impuri impurities ties will will not. not. (Pavi (Pavia, a, Lampman, Kriz, & Engel, 1999)
Figure 1 Structural formula of Aniline
Anil Anilin ine e is a prim primar ary y amin amine e in whic which h the the amin amino o grou group p is directly attached to the benzene ring and the final product of the reduction of
most nitrogen derivatives of benzene. Aniline is a colorless, oily, poisonous liquid that boils at 182°C when pure. The density of aniline is 1.0217 g/ml and its molecular weight is 93.13 g/mol. On standing in air and light, it gradually darkens in color due to oxidation due to atmospheric oxidation of an impurity commonly present in the benzene from which the aniline was prep prepar ared ed.. Ac Acet etyl ylat atio ion n is a reac reacti tion on in which which acety acetyll func functio tiona nall grou group p is introdu introduced ced into into an organi organic c compou compound. nd. Anilin Aniline e is acetyla acetylated ted by warmi warming ng mixture of aniline with acetic anhydride, acetyl chloride or even glacial acetic acid forming N-phenylacetamide, which is commonly known as acetanilide. (Wood, 1964)
Equation 1 Acetilation, a chemical reaction of Aniline with Acetic anhydride to produce Acetanilide and Acetic acid
Figure 2 Structural formula of Acetic anhydride
Acetic Acet ic anhy anhydr drid ide e is a colo colorl rles ess s liqu liquid id with with a pung pungen entt vinegar-like odor when it reacts with water to form acetic acid. The boiling poin pointt of acet acetic ic anhy anhydr drid ide e is 140° 140°C C and and the the melti melting ng poin pointt is -73° -73°C. C. It is soluble in ether, chloroform and benzene. It is soluble in water when acetic anhydr anhydride ide decomp decomposes oses.. The densit density y of acetic acetic anhydr anhydride ide is 1.082 1.082 g/ml g/ml in liquid state and its molecular weight is 102.09 g/mol. Acetic anhydride is most widely used for the conversion of cellulose to cellulose acetate, which is a component of photographic film and other coated materials. It plays an impo import rtan antt role role in the the acet acetyl ylat atio ion n of anil aniline ine to form form acetanilide. (ACETIC ANHYDRIDE (ACETYL ETHER))
Figure 3 Structural formula of Acetanillide
Acetanilide [C6H5NH(COCH3)] is the product of acetylation of aniline with acetic anhydride at low temperature. It is a white, odorless flake solid or crystals that boils at 304°C and melts in the range of 114-116°C. The density of acetanilide is 1.219 g/ml. Acetanilide is soluble in hot water, water, alcohol, ether, ether, chlor chlorof ofor orm, m, acet aceton one, e, glyc glycer erol ol and and benz benzen ene. e. It is stab stable le unde underr norma normall cond condit itio ion n and and can can und underg ergo self self-i -ig gnite nite at 545°C 45°C.. (AC (ACETAN ETANIL ILID IDE E (N(NPHENYLACETAMIDE)) Acetanilide is used as a precursor in penicillin synthesis and and othe otherr phar pharma maceu ceutic tical als s inclu includi ding ng paink painkil ille lers rs and and inte interm rmed edia iate tes. s. In
medicine, it is a prodrug with analgesic and properties which is in the same class of drugs par paracet acetam amol ol.. Ho Howe weve verr, dire direct ct appl applic icat atio ion n methm methmog oglo lobi bine nemi mia a and and dama damage ge liver liver and and PHENYLACETAMIDE))
antipyretic, or fever-reducing as acetaminophen, in generic, of acet acetan anil ilid ide e may may caus cause e kidn kidneys eys.. (ACE (ACET TANIL ANILID IDE E (N(N-
The object objective ives s of the experi experiment ment are as follow follow:: (1) to synthes synthesize ize acetan acetanilid ilide e by the acetyl acetylati ation on of anilin aniline; e; (2) to purify purify crude crude acetan acetanilid ilide e product by recrystallization; and (3) to calculate the percentage yield of pure acetanilide. II. II. Exp Experim erimen enta tall A corn grain amount of pure acetanilide was placed into each of the three test tubes. The first test tube contained 1-ml distilled water. The test tube was shaken and placed in a warm water bath (37 – 40°C) for 1 – 5 minu minute tes. s. Then Then,, it was cool cooled ed thro throug ugh h an ice ice bath bath.. So Solu lubi bili lity ty of pure pure acetanilide was recorded. For methanol and hexane, the same procedure was done. To produce produce crude acetanilide, acetanilide, a 20-ml distilled water and 2-ml aniline was place in an Erlenmeyer flask respectively. A 3-ml acetic anhydride was added slowly in the solution. All changes that occurred were noted. To hasten crystallization, it was placed in an ice bath then filtered to a wet filter paper. The crude acetanilide was dried and weighed using an analytical balance. A 20-ml recyrstallizing solvent was poured into the crude acetanilide. It was placed in a hot plate until the solid was dissolved. The solution was removed from the water bath when the solution was colored. A small amount of acti activa vate ted d char charco coal al was was adde added d to adso adsorb rb the the color colored ed impu impuri riti ties. es. The The solution solution was quickly subjected to filtration filtration while hot. The filtrate was placed in a receiver in a water bath to hasten recrystallization. The crystals were washed washed using using distill distilled ed water water. Then, Then, crysta crystals ls col collect lected ed were were dried dried throug through h pressing-in between filter paper. The pure acetanilide was weighed using an analytical balance. III. III. Resu Results lts and and Disc Discuss ussio ion n Recrystallizing solvent is a solvent that shows the desired solubility beha behavi vior or for for the the subs substa tanc nce e to be crys crysta tall lliz ized ed.. Iden Identi tify fyin ing g the the idea ideall recrys recrystall tallizi izing ng sol solven ventt of a compou compound nd is necessa necessary ry to purify purify the organi organic c compound. Trial-and-error method is commonly done when the compound to be puri purifi fied ed is unkn unknow own. n. In choo choosi sing ng the the recr recrys ysta tall llin inzi zing ng solv solven ent, t, the the compound compound should should be insolub insoluble le at roo room m temper temperatu ature. re. While While heatin heating, g, the compound compound should should be very very sol solubl uble e and upon coo cooling ling,, it is insolub insoluble. le. The unwant unwanted ed impuri impurities ties should should be soluble soluble at roo room m temper temperatu ature re or insolub insoluble le during heating. The applied amount of heat energy associated with a given temperature temperature in a given system is the heat capacity capacity.. (Mullin, (Mullin, 1961) It should not go beyond the melting point of the substance to be crystallized. If the boiling point of the solvent is high, the solid may melt in the solvent rather
than dissolve. In such case, the solid may oil out. Oiling occurs when the solid substance melts and forms a liquid that is insoluble in the solvent. When When cool coolin ing, g, the the liqu liquid id refu refuse ses s to crys crysta tall lliz ize; e; rath rather er,, it beco become mes s a supercooled liquid, or oil. Oils may solidify if the temperature is lowered, yet will not crystal crystalliz lize. e. (Pavi (Pavia, a, Lampma Lampman, n, Kriz, Kriz, & Engel, Engel, 1999) 1999) In additi addition, on, volati volatilit lity y of the sol solven ventt is a factor factor in select selecting ing the correc correctt recrys recrystall tallizi izing ng solvent. The solvent should be volatile enough to be easily removed from the solutio solution n after after crysta crystalli llizat zation ion.. Vola olatile tile sol solven vents ts having having low boilin boiling g point point is preferable. (Pavia, Lampman, Kriz, & Engel, 1999) The chemical reactivity of recrystallizing solvent should be low. It should neither decompose nor oxidize the desired substance. The solvent should not react with the compound to be purified. Thus, the desired substance may be contaminated with impurities. (Mullin, 1961) Table 1 Solubility of Pure Acetanilide in Different Solvent
Solvent
At ro room temp. Water Insoluble Methanol Soluble Hexane Insoluble
During Upon heating cooling Soluble Insoluble Soluble Soluble Insoluble Insoluble
On Table 1, there were three (3) solvent that was tested, distilled water, methanol and hexane. Methanol is soluble while hexane is insoluble in all system. system. This This shows shows that that acetan acetanilid ilide e that that will will be place place in this this sol solven ventt cannot undergo recrystallization. Nevertheless, recystallization will not occur. In addition, extra precaution must be taken because methanol and hexane are flammable and highly volatile. However, distilled water exhibits different resu result lt;; rathe atherr, it sho hows ws the the desir esired ed solu solubi bili litty behav ehavio iorr of an idea ideall recrystallizi recrystallizing ng solvent solvent for acetanilide. acetanilide. At room temperatur temperature e it was insoluble; during heating it was soluble; and when placed upon cooling it was insoluble. Water is quite suitable for melting points of pure organic compounds from about room temperature to about 70°C in heating water bath. Heat is generally absorbed when acetanilide is introduced to heating water bath. bath. The solute solute dissolv dissolves es in the sol solven vent. t. (Mullin (Mullin,, 1961) 1961) In acetyl acetylati ation on of aniline aniline with with acetic acetic anhyd anhydrid ride, e, yieldin yielding g acetan acetanilid ilide e exhibit exhibits s an exothe exothermi rmic c reaction. Exothermic reaction is the release of heat from the system. In case of cooling, the heat has to be removed from the system, the temperature is lowered. Thus, crystals form. Hastening crystallization is done through ice bath. This method decreases the solubility of acetanilide.
Table 2 The actual yield of crude and pure acetanilide, and the percent yield of pure acetanilide
Weight of the crude acetanilide Weight of pure acetanilide Percentage Yield
2.7370g 1.8997g 64%
The weight of the crude acetanilide is 2.7370g. Acetylation of aniline and acetic anhydride contains small amount of impurities that may affect the weight of the substance from crystallization. During recrystallization process, the solution was subjected to heating water bath. The recrystallizing solvent should not be enough to dissolve the substance. This is a common error that may reduce the solid yield returned into crystals. (Pavia, Lampman, Kriz, & Engel, 1999) During heating water bath in recrystallization, highly colored impurities may make the solution appeared colored. These colored impurities can often be removed by decolorization by using activated charcoal, often called Norit. A decolorizing step is performed only if the color is due to impurities, not to color the desired product, and if color is significant. Small amount of colored impurities will remain in solution during crystallization, making decolorizing step unnecessary. Activated charcoal adsorbs the impurities because it has a large surface area and it can remove impurities more effectively. Only small amount of activated charcoal should be added. Too much activated charcoal used will not only adsorb the impurities but also the desired product. When adding activated charcoal, be cautious so that the solution will not erupt. Using activated charcoal in a minimum amount may reduce the risk of lung irritation. (Pastro, John, & Miller, 1998) When When the the acet acetan anil ilid ide e was diss dissol olv ved, ed, the the solu soluti tion on sho houl uld d be immediately filtered while hot in an ice bath. Filtering is most effective way to remo remove ve solid solid impu impuri riti ties es,, espe especi cial ally ly when when decol decolor oriz izat atio ion n is appl applied ied.. The The solut sol utio ion n in the the flas flask k shoul should d be kept kept in its boili boiling ng point point tempe tempera ratu ture res s to preven preventt prema prematur ture e crysta crystalli llizat zation. ion. Premat Premature ure crysta crystalliz llizati ation on may contain contain some of the impurities from the solvent. Evaporation of solvent may initiate premature crystallization. Washing of crystals with cold recystallizing solvent was done to help reduce the amount of mother liquor retained by the mass of crystals. (Mullin, 1961) The mother liquor is the solution that remains in the crystals. (Pavia, Lampman, Kriz, & Engel, 1999) Distilled water was used for washing washing because because it is the recrystalliz recrystallizing ing solvent solvent for acetanilide. acetanilide. However, However, during filtration, some part of the solution was lost and was not subjected to fitration that resulted to reduction of the yielded pure acetanilide. Dryi Drying ng the the cryst crystal als s was was done done afte afterr filt filtra rati tion on.. The The most most comm common on method involves placing the crystals on a watch glass, a clay plate or a piece of paper paper and allowing allowing it to dry dry in air. Acetan Acetanilid ilide e crysta crystals ls were were dried dried by pressing-in of crystals with filter paper. During the process, some of the residue was not weighed because the particles were attached to some part of
the filter filter paper paper.. Rushin Rushing g the dryin drying g proces process s resulte resulted d to reducti reduction on of the yielded pure pure acetanilide. acetanilide. The weight weight of the pure acetanilide acetanilide was reduced reduced to 1.8997g. To calculate the percentage yield, the limiting reagent and theoretical yield should be identified. Limiting reagent is the reactant that is used up first in a reaction. (Chang, 2008) Theoretical yield is the maximum yield of pure pure crys crysta tals ls that that coul could d be obta obtaine ined d by coo cooli ling ng or evap evapor orat atin ing g a give given n solutio solution. n. This This refers refers to the quantit quantity y of pure pure crysta crystals ls deposi deposited ted from from the solution. (Mullin, 1961)
Calculate for the limiting reagent:
Thus, the limiting reagent reagent is aniline because because it needs 2.96g 2.96g with 3ml
to react
The percentage yield calculated is 93%. This is the pure acetanilide obtained from the 2ml aniline and 3ml acetic anhydride.
IV. IV. Refer eferen ence ces s
Books: Chang, R. (2008). General Chemistry: The Essential Concepts (5th Ed.). New York: McGraw-Hill. McGraw-Hill. Pg. 81-85 Mullin, J. W. (1961). Crystallization. London, England: Butterworth & Co. Pg. 1, 21, 29-35, 39-55, 57-58, 62, 120-121, 140-141 Pastro, D. J., John, C. R., & Miller, M. S. (1998). Experiment and Techniques in Organic Chemistry. New Jersey: Prentice Hall. Pg. 43-46 Pavia, D. L., Lampman, G. M., Kriz, G. S., & Engel, R. G. (1999). Organic Laboratory Techniques: Techniques: A Microscale Approarch (3rd Ed.). Harcourt College Publiser. Pg. 558-576 Wood, C. (1964). Organic Chemistry (2nd Ed.). London: Butterowowrths & Co. Pg. 139-140, 264-273 Web sites: ACETANILIDE (N-PHENYLACETAMIDE). (n.d.). Retrieved August 16, 2009 , from http://chemicalland21.com/lifescience/phar/ACET http://chemicalland21.com/lifescience/phar/ACETANILIDE.htm ANILIDE.htm ACETIC ANHYDRIDE (ACETYL ETHER). (n.d.). Retrieved August 16, 2009, from http://chemicalland21.com/petrochemical/ACETIC%20ANH http://chemicall and21.com/petrochemical/ACETIC%20ANHYDRIDE.htm YDRIDE.htm
