Formal Report Re Crystallization

Recrystallization of Ac etanilide

Reyes, K.B., Rivera, G.I., Samonte, A.A., Soliven, R.Y.*, Sotto, K.C. 2CMT, Faculty of Pharmacy, UST Abstract Recrystallization is the primary method for purifying solid organic compounds through the differences in solubility at different temperatures. The dissolved solid has a decreased solubility at lower temperature and separates from the solution as it is cooled. A small seed crystal is formed initially, and it then grows layer by layer. In this experiment, acetanilide was formed by the acetylation of aniline and acetic anhydride. The crude acetanilide was dissolved in a solvent in a hot water bath. The solution was then cooled in an ice bath as crystals start to form. As the compound formed crystals, molecules of other compounds dissolved in the solution are excluded from the growing layer of crystals; hence, pure acetanilide is formed.

Introduction Organic compounds that are synthesized in laboratories or isolated from natural recourses are often tainted by impurities. Recrystallization is a process that removes these impurities from solid organic compounds that are at room temperature. This process is built on the principle that the solubility of a compound increases with temperature and decreases as it cools down, into its crystal form. Very pure compounds can be made by recrystallization. A small pure seed crystal of the compound forms in the solution as it cools down after being heated. Additional molecules are attached to the crystal in uniform layers, forming a growing crystal lattice. Crystal molecules have a higher affinity for the same kind of  molecules than impurities. This process of  crystallizing removes one kind of molecule from the solution. Recrystallization is a method in which two crystallization processes were performed. It is usually known as the second crystallization. It depends on the difference of solubility of a substance in a hot and in a cold solvent. Solubility refers to the degree of  substance which is the solute to be dissolved in solvent. It is the main factor that affects crystallization. Prior to the recrystallization process, identifying the recrystallizing solvent is necessary. The substance to be crystallized must exhibit ideal solubility behavior in the chosen

solvent. Purification of substances can take place when both the substance to be purified and the impurities have similar solubility at its boiling point temperature; and the impurities correspond to only a small portion of the total solid. In this manner, the substance to be purified would be the only one crystallized.

Figure 1 Structure of Aniline Aniline     is a primary amine in which the amino group is directly attached to the benzene ring and the final product of the reduction of most nitrogen derivatives of benzene. It has a density of  1.0217 g/ml and a molecular weight of  93.13 g/mol. Aniline is a clear to slightly yellow liquid with a characteristic odor. It does not readily evaporate at room temperature. Aniline is slightly soluble in water and mixes readily with most organic solvents. It is used to make a wide variety of products such as polyurethane foam, agricultural chemicals, synthetic dyes, antioxidants, stabilizers for the rubber industry, herbicides, varnishes and explosives. When exposed to light and air, it slowly changes color. It darkens because

of atmospheric oxidation of an impurity usually present in the benzene from which the aniline was prepared. Aniline is acetylated by warming a mixture of aniline Nand acetic anhydride, forming  phenylacetamide, which is more commonly known as acetanilide.

Figure 2 Structural formula of Acetic anhydride Acetic Anhydride or Acetyl Ether is a clear, colorless liquid with a very pungent, penetrating, vinegar-like odor that combines with water to form acetic acid. It is soluble in ether, chloroform and benzene. It has a density of 1.082 g/ml and a molecular weight of 102.09 g/mol. Its boiling point is at 140°C while its melting point is at -73°C. Acetic anhydride is used in the manufacture of cellulose acetate having the application as a base for magnetic tape and in the manufacture of textile fibres. Also, it is heated with salicylic acid to produce acetylsalicylic acid (aspirin). It is also used in the manufacture of  pigments, dyes, cellulose and pesticides etc. Most importantly, it plays an important role in the acetylation of aniline to form acetanilide.

Figure 3 Structural formula of Acetanillide Acetanilide [C6H5NH(COCH3)] or NPhenylacetamide is the product of  acetylation of aniline with acetic anhydride at low temperature. It is an odorless, white flake solid or crystalline powder (pure form). Acetanilide is soluble in hot water, alcohol, ether, chloroform, acetone, glycerol, and benzene. It melts at a range of 114-116°C and boils at 304°C. It can

undergo self-ignite at 545 C, but is otherwise stable under most conditions. Acetanilide is used as an inhibitor of peroxides and stabilizer for cellulose ester varnishes. It is used as an intermediate for the synthesis of rubber accelerators, dyes and dye intermediate and camphor. It is used as a precursor in penicillin synthesis and other pharmaceuticals including painkillers and intermediates. Phenylacetamide structure shows analgesic and antipyretic effects; however, acetanilide is not used directly for it may cause methemoglobinemia (the presence of excessive methemoglobin which does not function reversibly as an oxygen carrier in the blood). The experiment aims to synthesize acetanilide by the acetylation of aniline, purify crude acetanilide product by recrystallization, and calculate the percentage yield of the pure acetanilide.

Methodology

A corn-grain amount of acetanilide was placed into each of the three test tubes. 1-ml of water was added to the first test tube. The test tube was shaken and placed in a warm water bath (3740°C) for 1-5 minutes. Then, it was cooled through an ice water bath. Observations were recorded. For the second and third test tubes, methanol and hexane were used respectively using the same procedure. To produce crude acetanilide, 2-ml of aniline and 20-ml distilled water were mixed in an Erlenmeyer flask. A 3-ml acetic anhydride was then added slowly into the solution. All changes that took place were noted. To hasten crystallization, the solution was placed in an ice bath then filtered through a wet filter paper. The crude acetanilide was dried and weighed by the use of an analytical balance. A 20-ml recyrstallizing solvent was poured into the crude acetanilide. It was then placed in a hot water bath until the solid dissolved.

If the solution is colored, it must be removed from the water bath and a small amount of activated charcoal must be added to adsorb the colored impurities. However, if the solution is colorless, it must be quickly filtered while still hot using a fluted filter paper. The filtrate was allowed to cool by placing the receiver in a beaker containing tap water. The crystals were collected, washed with distilled water and dried by pressing-in between filter paper. It was then placed inside the locker until next meeting. The pure acetanilide collected was weighed using an analytical balance. The melting point was likewise, determined.

crystallizes out, any remaining soluble impurities will remain dissolved in the solvent. Third, the solvent should not react with the compound being purified. The desired compound may be lost during recrystallization if the solvent reacts with the compound. Lastly, The solvent should be volatile enough to be easily removed from the solvent after the compound has crystallized. This allows for easy and rapid drying of the solid compound after it has been isolated from the solution. Solvent

R oom temp.

During heating

Upon cooling

Water

Insoluble

Soluble

Insoluble

Methanol

Soluble

Soluble

Soluble

Hexane

Insoluble

Insoluble

Insoluble

Results and Discussion

The primary step involved in recrystallization is selecting a suitable solvent. Recrystallizing solvent is a solvent that shows the desired solubility behavior for the substance to be crystallized. Identifying the ideal recrystallizing solvent of a compound is necessary to purify the organic compound. There are four important properties that you should look for in a good solvent for recrystallization. A compound usually exhibits one of  three general solubility behaviors: (1), the compound has a high solubility in both hot and cold solvent, (2), the compound has a low solubility in both hot and cold solvent, and (3), the compound has a high solubility in hot solvent and a low solubility in cold solvent. Solvents which exhibit the first two behaviors are not useful for recrystallizing a compound. The first characteristic of a good recrystallizing solvent is exhibited by a solvent showing the third behavior, that is, high solubility at high temperatures and low solubility at low temperatures. Second, the unwanted impurities should be either very soluble in the solvent at room temperature or insoluble in the hot solvent. This way, after the impure solid is dissolved in the hot solvent, any undissolved impurities can be removed by filtration. After the solution cools and the desired compound

Table 1 Solubility of Pur e Acetanilide in Diff erent Solvent Three solvents (distilled water, methanol, and hexane) were tested. As shown in Table 1, methanol is soluble and hexane is insoluble at room temperature, during heating, and upon cooling. Hence, acetanilide, when placed on these two solvents, cannot undergo recrystallization. Both methanol and hexane are flammable and volatile. Thus, extra caution must be utilized. However, distilled water exhibited a different result. At room temperature it was insoluble; during heating it was soluble; and upon cooling, it was insoluble. Water shows the desired solubility behavior of an ideal recrystallizing solvent. Absorption of heat is exhibited when acetanilide is placed in a hot water bath. Thus, the solute dissolves in the solvent. In contrast, the reaction of aniline with acetic anhydride, producing acetanilide exhibits release of heat or exothermic reaction. During cooling, the temperature is lowered so that heat shall be removed. Therefore, crystals form.

Hastening of crystallization is done through ice water bath which decreases the solubility of acetanilide. Weight of the crude acetanilide

2.24

Weight of acetanilide

1.00 g

Percentage Yield

pure

g

64%

Table 2 The actual yield of crude and pure acetanilide, and the percentage yield of pure acetanilide The weight of the crude acetanilide is 2.24 g. The acetylation of aniline and acetic anhydride would yield to acetanilide but it may contain small amount of  impurities which may affect the weight of  pure acetanilide. During recrystallization, the solution was placed in a hot water bath. It would be noted that the recrystallizing solvent is not enough to dissolve the substance which may result to reduction of the crystallized acetanilide. During the water bath in recrystallization, the solution would look as if it was colored because of impurities. These impurities may be decolorized by the use of activated charcoal which adsorbs impurities because it has a large surface area and it can remove impurities more effectively. However, just a small amount of activated charcoal should be added. Too much activated charcoal will also adsorb the desired substance. Filtration is the most effective way to remove unwanted impurities most especially when decolorization was utilized; hence, the solution should be immediately filtered in an ice water bath while still hot. Take note that premature recrystallization may occur when the solution in the flask was not kept in its boiling point temperature. Evaporation of  solvent may initiate premature crystallization. Mother liquor refers to the solution that remains in the crystals. To reduce the amount of mother liquor, washing of  crystals with cold distilled water must be done. However, during filtration, some

part of the solution was lost that resulted to reduction of the pure acetanilide. After filtration, the crystals were dried by pressing-in between filter paper. However, some were not weighed because the crystals were attached to some part of  the filter paper. The weight of the pure acetanilide collected was reduced to 1.00 g. To calculate the percentage yield, the theoretical yield and the limiting reagent must be first identified. The theoretical yield is the maximum yield of  pure crystals that could be obtained by cooling or evaporating a given solution. This refers to the quantity of pure crystals deposited from the solution. On the other hand, limiting reagent is the reactant that is used up first in a reaction.   

             

                         

Identify the limiting reagent:     

   







        





      

Hence, the Aniline (   ).

limiting

reagent

is

Theoretical yield = mass of LR 



  



 

 

    

The percentage yield based on the experiment is 49%. This is the pure

acetanilide obtained from the 2-ml aniline and 3-ml acetic anhydride. The melting point of pure acetanilide was also determined by immersing a capillary tube with pure acetanilide attached to a thermometer into an oil bath. The melting point of the crude acetanilide ranges from 115-118°C while the pure acetanilide melts at 110-116°C. Hence, the recrystallized acetanilide obtained is pure. Ref erences

Books: Bayquen, A., Cruz, C. et.al. (2009). Laboratory  M anual  in Organic  C hemistry . Philippines: C & E Publishing, Inc. Pg. 4748 Pavia, D. L., Lampman, G. M., Kriz, G. S., & Engel, R. G. (1999). Organic Laboratory Techniques: A Microscale Approarch (3rd Ed.). Harcourt College Publiser. Pg. 558576 Web sites:  ACET   ANI LIDE ( N-PH E NY L ACET   AM IDE). (n.d.). Retrieved August 21, 2010, from http://chemicalland21.com/lifescience/pha r/ACETANILIDE.htm  ACET IC      ANHYDRIDE (   ACET Y L ET H E R ). (n.d.). Retrieved August 21, 2010, from http://chemicalland21.com/petrochemical  /ACETIC%20ANHYDRIDE.htm PURIFYING  ACET   ANI LIDE BY  REC RYST   ALLIZAT IO   N. Retrieved August 22, 2010, from http://www.cerlabs.com/experiments/108 7540703X.pdf  REC RYST   ALLIZAT IO   N  SOLVE NT   .  Retrieved August 21, 2010, from http://jchemed.chem.wisc.edu/JCESoft/C CA/CCA6/MAIN/1ChemLabMenu/Separatin g/F_1SOLVE_MENU/F_1SOLVE/F_1SOLVE  _01/F_1SOLVE_10/MOVIE.HTM REC RYST   ALLIZAT IO   N 

Retrieved August 21, 2010, from http://www.chem.umass.edu/~samal/269  /cryst1.pdf