64349840-formal-report-re-crystallization-exp-4-final.docx

University of Santo Tomas Faculty of Pharmacy Organic Chemistry Laboratory RECRYSTALLIZATION OF ACETANILIDE Jane Catherine SP. Villanueva, Edenn Claudine C. Villaraza, Lorenz Oliver C. Villegas and Cristel Bernice T. Wee Group 10

2G-Medical Technology

Organic Chemistry Laboratory

ABSTRACT Recrystallization is one of the simplest and most widely used technique for purifying organic solids through the differences in solubility at different temperatures. It is also the process in which the solid to be crystallized is dissolved to either a hot solvent or a hot solvent mixture and is cooled in a solution. In this experiment, acetanilide, the crude product of acetylation of aniline and acetic anhydride, was used as the pure organic compound. Crude acetanilide underwent crystallization process using the preferred recrystallizing solvent, water. The crystallization process was when crude acetanilide was placed in hot water bath and was cooled after in an ice bath which would then yield to the formation of crystals of pure acetanilide. The percentage yield form the crude acetanilide was 73.72% while the percentage yield from pure acetanilide was 61.93%. The percentage recovery in the experiment was 84.00 %

INTRODUCTION Organic compounds that came from the nature, whether solid or liquid, contain impurities in them. Different purification methods can be used to remove the impurities present in a compound. For liquids, distillation is the most common used purification method. It separates volatile liquids on the basis of their boiling points. As for solids, either sublimation or Recrystallization can be used. Sublimation is only use for solids which can directly pass into vapor phase without passing through the liquid phase. On the other hand, Recrystallization involves solid which doesn’t have the same property of liquids used in sublimation. It is a method which purifies organic solids base on its solubility. It is also a process which dissolves solid to be crystallized in a hot solvent mixture and cools it afterward. The dissolve solid decreases in solubility at a low temperature and separates as it cools resulting to small seed crystals. Crystallization was done twice. During the first crystallization a crude product would be formed which would still have some impurities that needs to be remove. This was the reason for doing crystallization for a second time yield to a pure product which contained fewer or no impurities at all. The level of purity of the product can be checked through its melting point range. Formation of crystals was due to the difference in solubility of the solid with the solvent. Solutes or compounds tend to be more soluble in hot

solvents than they were in cold solvents. The crystals formed have a lattice structure that is a fixed and rigid arrangement of atoms, molecules or ions. Solubility refers to the degree of substance in which the solute is to be dissolved in solvent. It was the main factor that affects crystallization. Identifying the recrystallizing solvent was very important in crystallization process. The substance to be crystallized must exhibit ideal solubility behavior in the chosen solvent. Purification of substances could take place when both the desired substance and the impurities have similar solubility at its boiling point temperature; and the impurities correspond to only a small portion of the total solid. The desired compound will crystallize in cooling temperature while impurities will not.

Fig.1 Structure of Aniline Aniline (C6H5NH2) also known as aminobenzene or benzenamine 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. Its IUPAC name is phenlyamine, 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, 3.6g/100mL at 20°C, 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 it color and 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 and acetic anhydride, forming N-phenylacetamide, which is more commonly known as acetanilide.

Figure2. Structure of Acetic Anhydride Acetic Anhydride (C4H6O3) or Acetyl Ether or Acetyl Oxide 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 fibers. 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. Structure of Acetanilide

Acetanilide (C6H5NH(COCH3)) which has a IUPAC name of N-Phenylacetamide is the product of acetylation of aniline with acetic anhydride at low temperature. It is an odorless, white flake solid or crystalline powder. 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 also 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 objectives of the experiment were to synthesize acetanilide by the acetylation of aniline, to purify crude acetanilide product by recrystallization, and to calculate the percentage yield of the pure acetanilide.

EXPERIMENTAL A. Sample       

Used Acetic Anhydride Aniline Acetanilide Activated charcoal Methanol Hexane Water

B. Procedure 1. Determination of best and appropriate recrystallizing solvent A corn-grain size amount of crude acetanilide was put into three different test tubes. Distilled water was placed in one of test tube, hexane to another, and methanol to the last. They were then shaken well and were noted base

on each of its solubility of acetanilide. Afterwards, they underwent water bath for about 1-5 minutes, again, the solubility of acetanilide in its respective solvents under heat were noted. Immediately they were place onto an ice bath. For the last time, solubility of acetanilide in each test tube was noted. This process would determine the appropriate and the best solvent that would yield pure Acetanilide which came from the acetylation of Aniline and Acetic Anhydride. 2. First crystallization In an Erlenmeyer flask, 2ml of aniline, 20ml of distilled water and 3ml of Acetic Anhydride were added. Changes were noted. Afterwards the flask was placed in an ice bath to cool which would hasten the crystallization. When the crystals were fully formed, the solution was filtered to be able to obtain the formed crystals, the crude Acetanilide. Then the residue was dried by pressing the crystals with filter paper that will sip the remaining liquid, or leaving the crystals over-night for the liquid to evaporate on its own. When the crude Acetanilide was completely dry, it was weighed using the analytical balance.

Figure 4. Ice Bath Set-up 3. Second crystallization When the crude Acetanilide was completely dry, 20-mL of recyrstallizing solvent, water, was added. It was then placed in a hot plate until the solid was dissolved. Afterwards the solution was removed from the water bath, to be able to put a small amount of activated charcoal because the solution was colored. A small amount of activated charcoal was placed to absorb the colored impurities. Afterwards the solution was quickly subjected to filtration while hot. Allow it to cool then collect crystals. It was then washed by distilled water. Dry the residue just like the procedure in first crystallization by pressing the crystals with filter paper that would sip the remaining liquid, or leaving the crystals over-night for the liquid to evaporate on its own.

When the pure acetanilide was completely dry, it was then weighed using the analytical balance.

Figure 5. Filtration Set-up For the determination of the purity of the pure Acetanilide find its melting point and compare it with the theoretical melting point of a pure Acetanilide. Triturate the crystals using a mortar and pestle to produce a fine powder. In a capillary tube, put at least a centimeter of triturated pure Acetanilide. Put it in a oil bath and determine the melting point of the pure Acetanilide.

RESULTS AND DISCUSSION The first step involved in recrystallization was selecting the recrystallizing solvent for the solute. Recrystallizing solvent is a solvent that shows the desired solubility behavior for the substance to be crystallized. Trial-and-error method was commonly done when the compound to be purified is unknown. Identifying the ideal recrystallizing solvent of a compound was essential to purify the organic compound. A compound usually exhibits one of three general solubility behaviors. It is either the compound has a high solubility in both hot and cold solvent or it has a low solubility in both hot and cold solvent or it has a high solubility in hot solvent and a low solubility in cold solvent. The important properties for in a good solvent for recrystallization were exhibit by the third behavior. The compound should be insoluble at room temperature at the same time it should be very soluble during heating or at high temperatures and it should be insoluble upon cooling or at low temperatures. The unwanted impurities should also be considered. It must be either very soluble in the solvent at room temperature or insoluble in the hot solvent. This way, after the impure solid had dissolved in the hot solvent, any undissolved impurities could be removed by filtration. After the solution had cooled and the desired compound had crystallized

out, any remaining soluble impurities would remain dissolved in the solvent. Another thing needed to be considered was that the solvent should not react with the compound being purified. The desired compound could be lost during recrystallization if the solvent reacts with the compound. Lastly, the solvent must be volatile enough to be easily removed from the solvent after the compound has been crystallized. This would allow easy and rapid drying of the solid compound after it has been isolated from the solution. Solvent

Room temp.

During heating

Upon cooling

Water

Insoluble

Soluble

Insoluble

Methanol

Soluble

Soluble

Soluble

Hexane

Insoluble

Insoluble

Insoluble

Table1. Solubility of Pure Acetanilide in Different Solvent Three solvents namely distilled water, methanol, and hexane were used and tested to identify which solution would suit best for the experiment. As shown in Table 1, methanol was soluble in all temperature and hexane was insoluble in all temperature. Therefore these two solvents could not be used for acetanilide that would undergo recrystallization. Both methanol and hexane were also flammable and volatile. However, distilled water showed a different result and matched the behavior of an ideal recrystallizing solvent for acetanilide. At room temperature it was insoluble; during heating it was soluble; and upon cooling, it was insoluble. In conclusion, water was the desired solvent to be used in this experiment. The reaction of aniline with acetic anhydride had produced acetanilide which was crystals with some impurities. This exhibited exothermic reaction which means the release of heat from the system. To hasten crystallization, ice water bath was done which could easily decrease the solubility of acetanilide. During the process of cooling, the temperature had lowered which was a result of release of heat or an exothermic reaction. Therefore, crystals were formed again which means crystallization happened. These crystals were the crude acetanilide that was collected after the solution was filtered in a wet filter paper and the residue

was dried overnight. The residue contained the crude acetanilide which weighed 2.1897g. Weight of the crude acetanilide

2.1897 g

Weight of pure acetanilide

1.8394 g

Table 2. The weight of crude and pure acetanilide The collected crude sample still had some small amount of impurities which could affect the weight of pure acetanilide so recrystallization should be done. The solution which contained the crude acetanilide and water was placed again in a hot water bath. It would be noted that the recrystallizing solvent was enough to dissolve the substance which may result to reduction of the crystallized acetanilide. While water bathing took place, the solution would look as if it was colored. This was an effect of impurities. These impurities may be decolorized by the putting small activated charcoal which is a highly absorbent carbon. It was used as an effective adsorbent and purification or removal of impurities medium. This was because of its property of having large surface area and highly porous form. However, just specified small amount of activated charcoal should only be added because too much of it would absorb the desired substance too. Filtration was 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 it still hot. One should be cautious because premature recrystallization may occur when the solution in the flask was not kept in its boiling point temperature. 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 and were kept in the locker overnight. The dried crystals where then weighed in the analytical balance. The weight of the pure acetanilide collected was reduced to 1.8394 g. One reason that affected the reduction of pure acetanilide was the attachment of some acetanilide in which where not weighed.

To calculate the percentage yield, the theoretical yield which the limiting reagent was the basis 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. The solution below would indicate the limiting reagent and the theoretical yield of both the crude acetanilide and the pure acetanilide. 𝐶𝐻3 𝐶𝑂2 𝐻

𝐶6 𝐻5 𝑁𝐻2 + (𝐶𝐻3 𝐶𝑂2 )𝑂 →

𝐶𝐻3 • 𝐶𝑂 • 𝑁𝐻 • 𝐶6 𝐻5 + 𝐶𝐻3 𝐶𝑂𝑂𝐻

𝐴𝑛𝑖𝑙𝑖𝑛𝑒 𝑖𝑛 𝑔𝑟𝑎𝑚𝑠: 1.0217𝑔 2𝑚𝑙 𝐶6 𝐻5 𝑁𝐻2 × = 𝟐. 𝟎𝟒𝟑𝟒𝒈 1𝑚𝑙 𝐴𝑐𝑒𝑡𝑖𝑐 𝑎𝑛ℎ𝑦𝑟𝑑𝑟𝑖𝑑𝑒 𝑖𝑛 𝑔𝑟𝑎𝑚𝑠: 1.082𝑔 3𝑚𝑙(𝐶𝐻3 𝐶𝑂2 )𝑂 × = 𝟑. 𝟐𝟒𝟔𝟎𝒈 1𝑚𝑙 Identify the limiting reagent: 2𝑚𝑙 𝐶6 𝐻5 𝑁𝐻2 ×

1.0217𝑔 1𝑚𝑜𝑙𝑒 102.09𝑔 × × 1𝑚𝑙 93.13𝑔 1𝑚𝑜𝑙𝑒 = 𝟐. 𝟐𝟒𝒈 (𝑪𝑯𝟑 𝑪𝑶𝟐 )𝑶

1.082𝑔 1𝑚𝑜𝑙𝑒 1𝑚𝑜𝑙𝑒 × × 1𝑚𝑙 102.09𝑔 93.13𝑔 = 𝟐. 𝟗𝟔𝒈 𝑪𝟔 𝑯𝟓 𝑵𝑯𝟐

3𝑚𝑙(𝐶𝐻3 𝐶𝑂2 )𝑂 ×

Hence, the limiting reagent is Aniline (C6 H5 NH2 ). Theoretical yield = mass of LR Actual Yield = crude acetanilide 𝐴𝑐𝑡𝑢𝑎𝑙 𝑌𝑖𝑒𝑙𝑑 % 𝑌𝑖𝑒𝑙𝑑 = × 100 𝑇ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 𝑌𝑖𝑒𝑙𝑑 % 𝑌𝑖𝑒𝑙𝑑 𝑜𝑓 𝑐𝑟𝑢𝑑𝑒 𝑎𝑐𝑒𝑡𝑎𝑛𝑖𝑙𝑖𝑑𝑒 =

=

𝐴𝑐𝑡𝑢𝑎𝑙 𝑌𝑖𝑒𝑙𝑑 × 100 𝑇ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 𝑌𝑖𝑒𝑙𝑑

2.1897 𝑔 × 100 = 𝟕𝟑. 𝟕𝟐% 2.0434 𝑔

% 𝑌𝑖𝑒𝑙𝑑 𝑜𝑓 𝑝𝑢𝑟𝑒 𝑎𝑐𝑒𝑡𝑎𝑛𝑖𝑙𝑖𝑑𝑒 =

𝐴𝑐𝑡𝑢𝑎𝑙 𝑌𝑖𝑒𝑙𝑑 × 100 𝑇ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 𝑌𝑖𝑒𝑙𝑑

1.8394 𝑔 = × 100 = 𝟔𝟏. 𝟗𝟑% 2.0434 𝑔

Based on the experiment the percentage yield in crude acetanilide was 73.72% and in pure acetanilide was 61.93%. There was a reduction in weight on the pure acetanilide due to removal of weight of impurities. It was also because of some crystals which were dissolved and some which could not be separated in the filtration paper.

The percentage recovery of pure acetanilide from the crude acetanilide was also computed which is shown below. % Recovery =

mass of pure acetanalide × 100 mass of crude acetanalide

% Recovery =

1.8394 g × 100 2.1897 g

% Recovery = 84.00% The percentage recovery of pure acetanilide was 84.00% which means there was only a minimum amount of acetanilide lost and the experiment was a success. The pure acetanilide that was collected was colored white.

In conclusion, the more the solute had undergone recrystallization, the purer it get but the amount decreases.

REFERENCES: From books Martin & Gilbert (2011). Organic Laboratory Experiment (5th Ed.). Boston: Cengage Learning. University of Santo Tomas. Faculty of Pharmacy. Organic Chemistry Group. (2009). Laboratory Manual in Organic Chemistry. Quezon City: C&E Publishing Inc. Ault (1983). Techniques & Experiments fo Organic Chemistry (4th Ed.). Massachusets: Ally & Bacon Incorporated. From websites ACETANILIDE (N-PHENYLACETAMIDE). (n.d.). Retrieved August 12, 2011 from http://chemicalland21.com/lifescience/phar/ACET ANILIDE.htm

ACETIC ANHYDRIDE (ACETYL ETHER). (n.d.). Retrieved August 12, 2011, from http://chemicalland21.com/petrochemical/ACETI C%20ANHYDRIDE.htm PURIFYING ACETANILIDE BY RECRYSTALLIZATION. Retrieved August 12, 2011,from http://www.cerlabs.com/experiments/108754070 3X.pdf RECRYSTALLIZATION.Retrieved August 12, 2010, from http://chemistry.barnard.edu/orgolab/lab2 and http://web.centre.edu/muzyka/organic/lab/24_re crystallization.htm