EXPERIMENT 4 Recrystallization Dion S. Romero, Jonvi I. Romero, Dennis R. Rueda, Monica Lorraine L. Segismundo, and Catrina D.

Tan Group 8 2A Medical Technology Organic Chemistry Laboratory ABSTRACT

Recrystallization is a common method of purifying organic substances through the difference in solubility at different temperatures. In this experiment, Acetanilide was produced by Acetylation of Aniline with Acetic Anhydride. The crude Acetanilide was dissolved in a solvent in a heating water bath. The solution was cooled slowly in an ice bath as crystals form out. As the compound crystallizes from the solution, molecules of other compounds dissolved in solution are excluded from growing crystal lattice, yielding pure Acetanilide.

INTRODUCTION
Organic compounds that are solid at room temperature are usually purified by crystallization. Pastor, John and Miller (1998) define crystallization as the deposition of crystals from a solution. During the process of crystal formation, a molecule has the tendency to be attached to a better fit in a crystal lattice of a molecule of the same structure than for other molecules. Recrystallization is a way of effective recovery of a substance mixed with another to produce a pure compound. With their difference in solubility, one can separate them by dissolving the mixture, then filter out the impurities in the process. Pavia, Lampman, Kriz and Engel (1999) define recrystallization as a method in which two crystallization processes are performed; thus, it is referred to as the second crystallization. Recrystallization depends on the difference of solubility of a substance in a hot and in a cold solvent. Solubility is defined as the degree of substance, the solute, to be dissolved in a liquid solvent. It is the main factor that affects crystallization. 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. Aniline is a colorless, oily, poisonous liquid that boils at 182C when pure. The density of aniline is 1.0217 g/ml. It has a molecular weight of 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 prepared.

Figure 1: Structural Formula of Aniline

Acetic anhydride is a colorless liquid with a pungent vinegar-like odor when it reacts with water to form acetic acid. The boiling point of acetic anhydride is 140C, and the melting point is -73C. It is soluble in ether, chloroform and benzene. It is soluble in water when acetic anhydride decomposes. The density of acetic anhydride is 1.082 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 important role in the acetylation of aniline to form Acetanilide.

Figure 2: Structural Formula of Acetic anhydride

Acetylation is a reaction in which acetyl functional group is introduced into an organic compound. Aniline is acetylated by warming a mixture of aniline with acetic anhydride, acetyl chloride or even glacial acetic acid, forming Nphenylacetamide, which is commonly known as acetanilide. Acetanilide 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 304C, and melts in the range of 114116C. The density of acetanilide is 1.219 g/ml. Acetanilide is soluble in hot water, alcohol, ether, chloroform, acetone, glycerol and benzene. It is stable under normal condition, and can undergo

self-ignite at 545C. Acetanilide is used as a precursor in penicillin synthesis and other pharmaceuticals, including painkillers and intermediates. In medicine, it is a pro-drug with analgesic and antipyretic, or fever-reducing properties which is in the same class of drugs as Acetaminophen; in generic, Paracetamol. However, direct application of acetanilide may cause Methemoglobinemia, and damage liver and kidneys.

Figure 3: Structural formula of Acetanilide

This experiment was conducted for the accomplishment of the following objectives: (1) Synthesize acetanilide by the acetylation of aniline, and (2) Purify crude acetanilide product by recrystallization.

EXPERIMENTAL
A. Compounds tested Pure Acetanilide Samples used 2-mL Aniline, 3-mL Acetic Anhydride B. Procedure 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 40C) for 1 5minutes. Then, it was cooled through an ice bath. Solubility of pure acetanilide was recorded. For methanol and hexane, the same procedure was done. The group performed the experiment using a recrystallization set-up (Figure 4). 1. Acetylation To produce crude acetanilide, a 20-mL distilled water and 2-mL aniline was placed in an Erlenmeyer flask. 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. 2. Filtration It was filtered to a wet filter paper. The crude acetanilide was dried and weighed. 3. Recrystallizing solvent A 20-ml recrystallizing solvent was poured into the crude acetanilide. It was heated in a water bath until the solid was dissolved.
Figure 4: Recrystallization set-up

4. Addition of Activated Charcoal The solution was removed from the water bath if the solution was colored. A small amount of activated charcoal was added. Heating was continued. 5. Filtration The solution was quickly subjected to filtration while hot. It used a fluted filter paper. The filtrate was placed in a receiver in a water bath of tap water. The crystals were washed using distilled water. Then, crystals collected were dried through pressing-in between filter paper. 6. Determination of Melting Point The pure acetanilide was weighed. The melting point was determined.

RESULTS AND DISCUSSION

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 specific organic compound. In choosing the recrystallizing solvent, the compound should be insoluble at room temperature. While heating, the compound should be very soluble. Upon cooling, it is insoluble. The unwanted impurities should be soluble at room temperature or insoluble during heating. The applied amount of heat energy

associated with a given temperature in a given system is the heat capacity. 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 cooling, the liquid refuses to crystallize; rather, it becomes a super cooled liquid, or oil. In addition, volatility of the solvent is a factor in selecting the correct recrystallizing solvent. The solvent should be volatile enough to be easily removed from the solution after crystallization. Volatile solvents having low boiling point is preferable. 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. At room temperature insoluble soluble insoluble During heating soluble soluble insoluble Upon cooling insoluble soluble insoluble

done through ice bath. This method decreases the solubility of acetanilide. Weight of Crude Acetanilide Weight of Pure Acetanilide Percentage Yield 6.20g 0.60g 9.68%

Table 2: Actual yield of crude and pure acetanilide, and the percentage yield of pure acetanilide.

water methanol hexane

Table 1: Solubility of Pure Acetanilide in Different Solvents

On Table 1, there were three solvents that were tested: distilled water, methanol and hexane. Methanol is soluble, while hexane is insoluble in all systems. This shows that acetanilide that will be place in this solvent cannot undergo recrystallization. Nevertheless, recrystallization will not occur. In addition, extra precaution must be taken because methanol and hexane are both flammable and highly volatile. However, distilled water exhibits different result; rather, it shows the desired solubility behavior of an ideal recrystallizing solvent for acetanilide. At room temperature 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 70C in heating water bath. Heat is generally absorbed when acetanilide is introduced to heating water bath. The solute dissolves in the solvent. In acetylation of aniline with acetic anhydride, yielding acetanilide exhibits an exothermic 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

The weight of the crude acetanilide is 6.20g. 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. 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. 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. According to Pastor, John and Miller (1998), 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. When the acetanilide was dissolved, the solution should be immediately filtered while hot, and put in an ice bath. According to Pavia, Lampman, Kriz and Engel (1999), filtering is most effective way to remove solid impurities, especially when decolorization is applied. The solution in the flask should be kept in its boiling point temperatures to prevent premature crystallization. Premature crystallization may 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. The mother liquor is the solution that remains in the crystals. Distilled water was used for washing because it is the recrystallizing solvent for acetanilide. However, during filtration, some part of the solution was lost and was not

subjected to filtration that resulted to reduction of the yielded pure acetanilide. Drying the crystals was done after filtration. The most common method of drying the crystals involves placing the crystals on a watch glass, a clay plate or a piece of paper, and allowing it to dry in air. Acetanilide crystals were 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 paper. Rushing the drying process resulted to reduction of the yielded pure acetanilide. The weight of the pure acetanilide was reduced to 0.60g. According to Chang (2008), 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. 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. Calculations: % w/w yield Acetanilide = Ay/Ty x 100 = 0.6g/6.2g x 100 = 9.68%
where in: Ay = Actual yield Ty = Theoretical yield

http://chemicalland21.com/petrochemical/ACETI C%20ANHYDRIDE.htm

REFERENCES
Books:

Chang, R. (2008). General Chemistry: The Essential Concepts (5th Ed.). New York: McGraw-Hill. Pastor, D.J., John, C.R., & Miller, M.S. (1998). Experiment and Techniques in Organic Chemistry. New Jersey: Prentice Hall. Pavia, D.L., Lampman, G.M., Kriz, G.S., & Engel, R.G. (1999). Organic Laboratory Techniques: A Microscale Approach (3rd Ed.). Harcourt College Publiser.
Websites:

ACETANILIDE (N-PHENYLACETAMIDE). (n.d.). Retrieved August 2, 2013 from http://chemicalland21.com/lifescience/phar/ACET ANILIDE.htm ACETANILIDE ANHYDRIDE (ACETYL ETHER). (n.d). Retrieved August 2, 2013 from