Synthesis of Acetanilide by the Acetylation of Aniline with Acetic Anhydride and Purification of Crude Acetanilide through Recrystallization.

Cyril Oliveros, Jamille Ong, Zeus Punzalan, Yvanne Rabe, Lynzee Reyes Group 7, 2D-Pharmacy, Faculty of Pharmacy, University of Santo Tomas

Abstract
Recrystallization is a process of dissolving the solid to be crystallized in a hot solvent or solvent mixture and then cooling the solution slowly. On the given experiment, aniline is mixed with water then is slowly added with acetic anhydride, undergoing acetylation thus producing crude acetanilide. The crude acetanilide is then dissolved in a solvent, particularly water, in a water bath. After heating, the solution is quickly filtered using a fluted filter paper and cooled. The resulting filtrate is the pure acetanilide.

Introduction Solids not having the property to sublimate can be purified through the recrystallization method. Recrystallization is the primary method for purifying solid organic compounds. Compounds obtained from natural sources or from reaction mixtures almost always contain impurities. The impurities may include some combination of insoluble, soluble, and colored impurities. To obtain a pure compound these impurities must be removed. Each is removed in a separate step in the recrystallization procedure. Crystallization plays an important role in the synthesis, scale-up, processing, formulation, and stability of active pharmaceutical ingredients (API) Before the actual recrystallization was done, selection of the proper solvent was performed. The solvents to be tested were water, methanol, and hexane. Each of which was tested at room temperature, at heating and cooling. Choosing the proper solvent is important because it helps the experiment produce a higher yield. Acetic Anhydride 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.

Figure 1 Skeletal Structure of Acetic Anhydride

Aniline, a primary amine where the amino group is directly attached to the benzene ring and the final product of the reduction of most nitrogen derivatives of benzene. It is also used as organic base used to make dyes, drugs, explosives, plastics, and photographic and rubber chemicals.

Figure 2 Skeletal Structure of Aniline

Acetanilide is an odorless, white flake solid or crystalline powder (pure form); soluble in hot water alcohol, ether, chloroform, acetone, glycerol, and benzene; melting point 114C and boiling point 304C; can undergo selfignite at 545C, but is otherwise stable under most conditions.

An ice bath was conducted after to hasten crystallization. The solution was then filtered through a wet filter paper. The filtrate was dried and weighed. The product is the crude acetanilide.
Figure 3 Skeletal Structure of Acetanilide

Materials and Methods

Materials The experiment made used of test tubes for the selection of solvents. The solvents tested were water, hexane and methanol. We also used an Erlenmeyer flask, Bunsen burner, tripod, wire gauze, filter paper and beaker for the recrystallization experiment proper. The chemicals involved were Aniline and Acetic Anhydride.

20mL of the recrystallizing solvent, which is water, was poured into the crude acetanilide. Then it was heated on a water bath until all the solid dissolved. If the resulting solution is colored, activated charcoal was added and continued heating. After heating, the solution is quickly filtered using a fluted filter paper and cooled. Then it was cooled by placing the receiver in beaker containing tap water.

Method A corn-grain amount of pure acetanilide was placed in each of three test tubes. For the first test tube, 1 mL of water was added. It was shook and placed in a warm water bath, 3740C, for 1-5 min. Then it was allowed to cool. The observations were recorded. This was done likewise on the other two solvents. The resulting experiment lead to the conclusion that water is the suitable solvent for the recrystallization of acetanilide since none of the other solvents except water dissolved acetanilide at room temperature. After selection of the suitable solvent, the recrystallization experiment was done. 2 mL of aniline was mixed with 20 mL of distilled water. Then 3 mL of acetic anhydride was slowly added.
Figure 4 Filter after heating with activated charcoal

The crystals are collected, washed with distilled water, dried and weighed. The final product is the pure acetanilide.

Figure 5 Pure Acetanilide

Results and Discussion The first step for recrystallization is identifying for the

suitable solvent. Recrystallizing solvent is a solvent that shows the desired solubility behaviour for the substance to be crystallized. The solvent for acetanimide needs to be insoluble at room temperature and upon cooling but soluble during heating.

Solvent Water Methanol Hexane

at room temperature Insoluble Soluble Insoluble

during heating Soluble Soluble Insoluble

upon cooling Insoluble Soluble insoluble

The weight of the crude acetanilide is 3.5 g. Acetylation of aniline and acetic anhydride yields acetanilide but may contain impurities that affect the weight of the substance. The solution was placed in hot water bath during the recrystallization process. The recrystallizing solvent is not enough to dissolve the substance which is a common error to reduction of the crystallized acetanilide. The impurities during water bath in recrystallization make the solution colored. This was decolorizes with the use of activated charcoal, since activated charcoal adsorbs impurities because it has a large surface area. Still, only a small amount of activated charcoal should be used, any larger amount would adsorb even the desired substance. After the acetanilide is dissolved, it should be quickly filtered while hot. This is needed because if it cooled down, it may undergo premature crystallization. The crystals are then washed with cold distilled water to reduce the amount of mother liquor retained by the mass of crystals. However, during filtration, parts of the solution were lost and did not undergo filtration which resulted to a reduction of the pure acetanilide. After filtration, the crystals were dried by placing them on an evaporating dish and place on a hot plate. The weight of the pure acetanilide collected is 1.89g. The limiting reagent and the theoretical yield is then identified to calculate the percentage yield. The limiting reagent is the substance totally consumed when the chemical reaction is complete. The theoretical yield is the
the maximum yield of pure crystals that

Table 1 Various Solvents for Pure Acetanilide

From the given table, water is the suitable solvent since it is insoluble both at room temperature and upon cooling and soluble during heating. Methanol is soluble at all systems and hexane is insoluble in all systems. When acetanilide is placed on a water bath, there is absorption of heat, resulting to acetanilide being dissolved in the solvent. On the other hand, when aniline reacts with acetic anhydride, it produces acetanilide that exhibits the release of heat or exothermic reaction. During cooling, the low temperature removes the heat, thus, producing crystals. Hastening of crystallization is done through ice bath. This makes the solubility of acetanilide decrease. Weight of crude acetanilide the 3.5g

Weight of the pure acetanilide

1.89g

Table 2 Weight of Crude and Pure Acetanilide

could be obtained by cooling or evaporating a given solution.

References
CH3CO2 C6H5NH2 + (CH3CO2)O H CH3 CO NH C6H5 + CH3COOH

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Aniline in Grams 2 mL C6H5NH2 x = 2.0434 g

Acetic Anhydride in Grams 3 mL (CH3CO2)O x = 3.2460 g

Limiting Reagent: 2 mL C6H5NH2 x x

= 0.0219 moles C6H5NH2 3 mL (CH3CO2)O x x

= 0.0318 moles (CH3CO2)O The limiting reagent is Aniline. Theoretical yield - mass of limiting reagent % Yield = = = 171% The percentage yield is 171%. The calculated percentage yields error is based on the impurities found on the crude acetanilide. The melting point of the acetanilide is not determined on the experiment. x 100 x 100