CHY 224 - Multistep Synthesis of Acetylsalicylic Acid 2012

Multistep Synthesis of Acetylsalicylic Acid Student name: Lab partner: CHY224, Section 011 November 20, 2012 TA: Rob Denning Aspirin righttop Introduction and Background Many years ago, the compositions of many analgesic drugs had been known to contain some of bark and leaves of willow tree for the purpose of treatment from pain and fever1. In the 19th centuries, a group of scientist had discovered a salicylic acid as an active ingredient natural existing substance in willow plants in which used as treatment of a pain reliever1. However, the use of aspirin was first isolated in 1897 by the chemist Felix Hoffmann after he had studied and modified Gerhardt synthesis of acetylsalicylic acid1. Felix; however, had found that salicylic acid was causing stomach irritation thus; he replaced alcohol functional group in salicylic acid with ester1. Acetylsalicylic acid or best known as aspirin is a salicylate medication that commonly used and found in every households across the world because of it beneficiary use1. Aspirin is used as analgesic to relieve pain, aches, reduce body fever. A recent study had shown that aspirin may be used at low doses to help prevent the development of cardiovascular disease such as heart attack and stroke. However, the purpose of this lab was to demonstrate a multistep synthesis of aspirin experimentally to determine the purity, theoretical and percentage yield as well as the efficiency in obtaining the yield. This lab, therefore, divided into three parts. Firstly, the reaction of the methyl salicylate acid with sodium hydroxide 5M and sulfuric acid 1M to produce a salicylic acid of yield 58%. In the second part of the experiments, salicylic acid reacted with acetic anhydride and sulfuric acid as catalyze to increase the yields in 50oC to make a acetylsalicylic acid. In the last part of the experiment, the purification of aspirin and salicylic acid was confirmed using three different techniques which were ferric chloride test, thin layer chromatography (TLC) and the determination of the Pka. In the other hand, the melting point and TLC plates have been used to determine and compare the literature value and the purity of the compounds. The melting point determination is a method that used to determine the purity of the compounds by obtaining the range of the crude and purified substance and compared it to the literature value. The melting point of pure aspirin that obtained in this lab was (136-138oC) a sharp range with difference of 2oC, which is in the recorded actual value of 136oC that is in return, had confirmed the purity of the compound. The crude aspirin on the other side had a broad range of (134-144oC) comparing to recorded literature value that indicated that the crude aspirin was impure. Thin layer chromatography (TLC) is a technique that goes back to several years ago and it used to determine the purification. One of the important parts in performing the TLC analysis is to calculate the Rf value. Compounds with different chemical properties can have different polarity which can be observed by measuring the travel distance that the compound had taken in the developed chamber and divided it by the solvent travelled distance. In this experiment, one TLC plate 5x10cm was used to confirm the purity of the aspirin. After the plate had developed in a solution of 50% ethyl acetate/50% hexane, the spots were visualized under a UV light to observe and calculated their travelling distance. Recrystallization and vacuum filtration are other techniques that had been used in this lab to determine the purity of the aspirin and salicylic acid. After the crude aspirin had determined, the crude product isolated by filtration and purified by recrystallization. The yield percentage of aspirin was 79% which was a good result and indicated that efficiency was good during the synthesis of aspirin. Finally, the ferric chloride test was used to determine the purity of aspirin after adding 10 drops of methanol ferric chloride to a pure aspirin and observe any changes in colour. The colored of the pure aspirin was gold the same as the blank ferric solution that confirmed that aspirin had no reacted salicylic acid and therefore it pure. The Pka determination was the last part in the experiments that had used to obtain the amount of the acidity of aspirin. After determining the PH value of each of the aspirin and salicylic acid (2.92 and 2.59) respectively using digital PH meter, the Pka had calculated and recorded to be (3.65 and 5.4) respectively that indicated that aspirin and salicylic acid are both weak acids. Figure 1. A balanced chemical reaction for the hydrolysis of methyl salicylate acid. Figure 2. a balanced chemical reaction for the acetylation of salicylic acid Experimental Details Cautions Sodium Hydroxide 5.0M (NaOH) corrosive base (alkalis) .Avoid contact with eye and skin it can cause severe skin burns and permanent blindness2. Eye and skin contact: wash thoroughly with water for about 15 minutes2. Sulfuric Acid 1.0 M (H2SO4 ) highly corrosive acid. Avoid contact with clothes, skin and eye it may cause server skin burns and irritations to eye2. Eye and skin contact: wash carefully with water for about 10-15 minutes2. Acetic anhydride (C4H6O3) corrosive liquid that can releases irritant vapors may be harmful if inhaled and may cause skin burns avoid contact with skin and clothes2. Skin contact: wash with soap and water for about 20 minutes2. Eye contact: wash with water for about 20 minutes2. Materials and Apparatus Hot plate Scoopula Various sizes of beaker (250mL, 100mL,400mL,600mL) Graduated cylinder (10mL,) Erlenmeyer flask (125mL) Ice- water bath Watch glass Eye dropper Glass stirring rod UV light TLC plate Rack of test tubes Simple Reflux Apparatus Reflux condenser Heating mantle Retort stands 250 mL round-bottom flask Clamps 2-Hoses Ground glass joint Fisher- Johns Melting Point Apparatus Glass cover slip Vacuum Filtration Apparatus Rubber collar Vacuum flask Filter paper Clamps Retort stand Buchner Funnel Digital PH Meter Apparatus Measuring probes (glass electrode) Producers Part A: Hydrolysis of Methyl Salicylate A mixture of Methyl salicylate of (0.040mol, 6.086g), ester and a (50mL) solution of 5M NaOH was added into a (250mL) a tared round bottom flask. A reflux condenser was then attached to the reaction flask , the ground glass joints were tightly greased to prevent any gaseous solvent from escaping and then the reaction mixture was firmly clamp to the retort stand. The solution mixture was then heated at a temperature of its boiling point till the white solid that was formed during the addition of the reactions solutions was completely dissolved. A couple of boiling chips was added to the reaction mixture to prevent bumping when the solution was heated. The rate of heat was controlled to ensure the reflux level in the center of the condenser. After, the solution was heated for approximated 20 minutes; the mixture was allowed to cool at room temperature. The solution then was transferred into beaker of (250mL) and a volume of (135mL) of sulfuric acid of (1M) was added to make the solution acidic to litmus paper. The test technique for litmus paper that used was by dipping a glass rod into the mixture and then dabbed onto the litmus paper. A beaker of (600mL) was prepared as an ice-water bath to cool the solution as it was acidifying. Then, a (15mL) of sulfuric acid was added to the solution after the litmus turned to pink in order to precipitate the salicylate acid from the mixture. The mixture was cooled to crystallize in the ice-water bath to about (0oC). The product was collected through vacuum filtration using a Buchner funnel with filter paper. The crude salicylic acid was weighted as (5.14g). A hot solution filtration was then performed on a hot plate to purify crude salicylic acid and a fluted filter paper funnel was used to insure that the crystal not formed in the stem clogged funnel during the hot gravity filtration. The crystal was washed with (10 mL) of hot water to dissolve the remaining crystals in the filtration. The purified salicylic acid was then dried at in oven set of (70oC) for about 10-15mintues. After, the crystalized dried and cooled, the mass of the purified salicylic acid was (3.2g) and the parentage yield was calculated. A few (mg) amounts of the crystal and crude of salicylic acid were set aside to determine its melting point and TLC analysis. The melting point range of the crude salicylic acid determined was (151-163oC) and while the melting point range of the purified salicylic acid measured was (158-160oC) with crude yield (84%) and purified product yield (53%).The recrystallized salicylic acid was stored till the next week of the next step of synthesis. Part B: Acetylation of Salicylic Acid A warm water bath of (100mL) of distilled water was prepared in (400mL) beaker that contained a few boiling stones by heating it on a hot plate at temperature of (45-50oC). Acetic anhydride (4.93mL) was carefully added to (100mL) beaker containing salicylic acid. The mixture was stirred together using glass rod. Concentrated sulfuric acid (0.3mL, 0.0056mol) was then carefully added to the mixture. The mixture was stirred in a warm water bath for 15 minutes, till a clear solution of the mixture was observed. Gradually, the mixture was allowed to cool at a room temperature after removing the beaker from the water bath and covering it with a watch glass. The crystal of acetylsalicylic acid was formed, when the mixture reached a room temperature. After the crystallization was completely formed, a (50mL) of ice cold water was carefully added to quench any remaining acetic anhydride. The solution was cooled in an ice bath till the mixture became a semi-solid mass. The crystal acetylsalicylic acid was isolated via vacuum filtration and washed out several times with ice cold distilled water of (10mL) and dried for approximate (5 minutes) to obtain 3.3g of crude acetylsalicylic acid ,m.p= 134-144oC.Then, the crude acetylsalicylic acid product was placed into a (250mL) beaker , and (18mL) of hot water was added to cover the crude product. The solution was brought to boil; plenty of water was added to the dissolve the crude product completely without any leftover. The mixture was filtered through a hot filtration after removing it from the hotplate. After that, the mixture was left to gradually cool at a room temperature, and then allowed to cool in an ice water bath to crystalize. The crystalized acetylsalicylic acid was isolated by vacuum filtration, then rinsed with ice cold distilled water, and dried for 5 minutes to get 2.3g with yield ( 79%) and melting point of (136-138oC). The samples were placed and labelled in a beaker to be used in the next experiments synthesis. Part C: Analysis of Acetylsalicylic Acid A small spatula-tipful of each of crude salicylic acid, pure salicylic acid, crude acetylsalicylic acid and pure acetylsalicylic acid had been added to four small test tubes that clearly labelled. A (1mL) of methanol had been added to the four test tubes, then the tubes were carefully swirled to get a clear solution. One TLC plate of (5 x 10cm) prepared to run and analyze five solutions (crude salicylic acid, pure salicylic acid, crude acetylsalicylic acid, pure acetylsalicylic acid and methyl salicylate). Above the bottom of the plate about (10 to 15mm) a pencil baseline had drawn to space out five pencil hatchmarks in order to spot each of the five solution mentioned above. The five samples were spotted on their clearly labelled hatchmarks as (CS, PS, CA, PA, and M) for crude salicylic acid, pure salicylic acid, crude acetylsalicylic acid, pure acetylsalicylic acid and methyl salicylate respectively. A (600mL) beaker was prepared as developed chamber and then a circle of paper towel was placed inside the bottom of the beaker to prevent the plate from sliding while it developing. Then, the TLC plate was placed carefully into a developing chamber of 50% ethyl acetate/ 50% hexane in (600mL) beaker for about (3-5 minutes). The solvent front was marked with a pencil line while it still wet when it reached the top of the plate with (10mm) from the top edge of TLC plate. After that, the plate was allowed to dry and the spots were drawn in pensile while it visualized under the UV illumination. The Rf values of each of the five compounds were calculated to confirm the purity of the samples. The Rf for crude and pure salicylic acid were computed as (0.28 and 0.19) respectively which confirmed the purity of the crystalized salicylic acid that obtain in part a of the experiments because it had lower travelled distance comparing with the crude salicylic acid. The larger Rf of a compound the less pure the substance would be. Seven small test tubes were clearly labelled and contained a spatula-tipful of each of the samples (crude salicylic acid, pure salicylic acid, crude aspirin, pure aspirin, methyl salicylate acid, phenol and benzoic acid). The mixture stirred gently to obtain a clear solution after adding a (0.5 mL, 10 drops) of ferric chloride to each of the seven test tubes. The change in colour of the crude salicylic acid (dark brown) and methyl salicylate (dark brown close to black) was occurred rapidly as the ferric chloride added to it which in return confirmed the existing of phenol (hydroxyl group ) in each of the impure compounds. The colours of the pure aspirin remained unchanged (light gold close to the blank colour) when the ferric chloride is added to it which confirmed that aspirin was pure. Then, after the determination of the ferric chloride test the, rack of the seven test tubes were cleaned thoroughly with soap and water and the solutions in the test tubes were disposed in the organic waste container. A mass of (0.1023g and 0.1035) of pure salicylic acid and pure aspirin were weighed in analytic balance and placed in 250mL beaker. A 100 mL of distilled water was added to each beaker and then the mixture stirred carefully in order to get clear solutions. The PH value of each of the pure aspirin and salicylic acid measured using PH meter were (2.92 and 2.59) respectively. The PH and concentration of the product and the reactant that involved in each of the reactions thus, were computed in order to computing the Pka values. Aspirin had a Pka value of 3.56 whereas pure salicylic acid Pka was 5.2 which confirmed that the aspirin was a stronger acid than salicylic acid. Observations and Calculations Calculations of part a: *All the literature m.p and density had been recorded from the Merck index. Table1. Reactant involved in part a) Hydrolysis of Methyl Salicylate Reactant molecular formula Structural formula Mass used (g) Volume used (mL) M.W (g/mol) Mole used m.p (oC) Density (g/mL) Methyl salicylate C8H8O3 6.086 5.18 152.16 0.04 -9 1.174 Sulfuric acid H2SO4 14.712 150 98.08 0.15 10 1.84 Sodium hydroxide NaOH 10.00 50 39.997 0.25 318 2.13 1L=1000mL V H2SO4= (150mL)*(1L/1000mL) = 0.15L n H2SO4= C (M)* V (L) = (1mol/L)*(0.15L) =0.15mol m H2SO4 = n* M.W = (0.15mol) *(98.08g/mol) =14.712 g n NaOH= C(M)* V (L) = (5mol/L)*(0.05L) =0.25mol m NaOH = n* M.W = (0.25mol) *(39.997g/mol) =10.0 g Mass C8H8O3 = n *M = (0.04mol)* (152.16 g/mole) =6.0864 g Volume used C8H8O3 = mass/density = (6.0864g)/ (1.174 g/mL) = 5.1843 mL Table2. Product part a) hydrolysis of methyl salicylate Compound Mass (g) m.p range(oC) Thero. yield Actual yield Yeild Litr. Found (g) (mol) (g) (%) Crude salicylic acid 5.14 159.0 (151-163) 6.0864 _____ 5.14 84% purified salicylic acid 3.2 159.0 (158-160) 6.0864 0.02317 3.2 53% The calculation below showing how the theoretical yield was computed; C8H8O3 + 2NaOH C7H6O3 + 2NaHSO4 0.04 mol 0.25 mol 0.0231mol Salicylic acid was the limiting reagent since it had the lowest number of moles. % Yield of crude salicylic acid = [Actual yield (g)/ Theoretical yield (g)]*100% = (5.14g /6.0864g)*100% =84% % Yield of pure salicylic acid = [Actual yield (g)/ Theoretical yield (g)]*100% = (3.2g /6.0864g)*100% =53% n salicylic acid=m/M.W = (3.2g)/ (138.12g/mol) =0.02317mol Calculation of part b): Table1. Reaction and product carried out in part b) Acetylation of salicylic acid Reactant Structural Formula Mass used (g) Volume used (mL) M.W (g/mol) Density (g/mL) Mole used m.p (oC) Salicylic acid C7H6O3 2.9 2.0 138.12 1.44 0.021 159.0 Acetic anhydride C4H6O3 5.32 4.93 102.09 1.08 0.0521 -73.1 Sulfuric acid H2SO4 0.552 0.3 98.08 1.84 0.0056 10.0 n C7H6O3 = m/M.W = (2.9g)/ (138.12g/mol) =0.021mol V C7H6O3 = m/D = (2.9g) / (1.44g/mL) =2.0mL m C4H6O3 = V* D = (4.93mL) *(1.08g/mL) =5.3244 g n C4H6O3 = m /M.W = (5.32g) / (102.09 g/mol) =0.0521mol Volume used H2SO4 1 drop = 0.05mL 6 drops= V (mL)? V= (0.05mL*6 drops)/ (1drops) = 0.3 mL m= V*D = (0.3mL)*(1.84g/mL) =0.552 g n=m/M.W = (0.552g)/ (98.08g/mol) = 0.0056mol Table2. Product of the involved in the acetylation of salicylic acid Compound Mass (g) m.p range(oC) Thero. yield Actual yield Yeild Litr. Found (g) (mol) (g) (%) Crude acetylsalicylic acid 3.3 136 (134-144) 3.3 _____ 2.9 113.8% purified acetylsalicylic acid 2.3 136 (136-138) 2.3 0.01277 2.9 79% C7H6O3 + C4H6O3 C9H8O4 + C2H4O2 catalyst (50oC, 15 min) 0.021 mol 0.0521 mol 0.01277mol Acetylsalicylic acid was the limiting reagent since it had the lowest number of moles. % Yield pure salicylic acid = [Actual yield (g)/ Theoretical yield (g)]*100% = (2.9g /6.0864g)*100% =48% % Yield pure acetylsalicylic acid = [Actual yield (g)/ Theoretical yield (g)]*100% = (3.3g /2.9g)*100% =113.8% % Yield pure acetylsalicylic acid = [Actual yield (g)/ Theoretical yield (g)]*100% = (2.3g /2.9g)*100% =79% n pure aspirin=m/M.W = (2.3g)/ (180.17g/mol) =0.01277mol Calculation of part C: Table 1 part C) the PH determination of the pure compound Compound name and Molecular formula Structural Formula of the compound m.p range (oC) PH liter. Found Pure Salicylic Acid C7H6O3 (158-160) 2.4 2.59 Pure Acetylsalicylic Acid C9H8O4 (136-138) 2.24 2.92 The mass of the salicylic acid determined experimentally was 0.1023g n C7H6O3 =m/M.W = (0.1023g)/ (138.12g/mol) =0.000741 mol V(mL)= m(g)/D(g/mL) =(0.1023)/(1.44) =0.071mL C (M)=n/V =(0.000741mol)/(0.071mL) =0.01043M PH found = 2.59 [H3O+]=10-PH = 0.00257 M C7H6O3 + 3H2O C7H6O3 + 2H3O+ I 0.01043M 0M 0M C -0.00257 +2(0.00257) +0.00257 E 0.00786 0.00514 0.00257 Ka= [C7H6O3 ] [H3O+ ]2 /[ C7H6O3 ] = [(0.00514) (0.00257)2] /( 0.00786 ) = 4.3*10-6 PKa = -log [Ka] = 5.4 The mass of the acetylsalicylic acid determined experimentally was 0.1035g n C7H6O3 =m/M.W = (0.1035g)/ (180.17g/mol) =0.000574 mol V(mL)= m(g)/D(g/mL) =(0.1035)/(1.08) =0.09583mL C (M)=n/V =(0.000574 mol)/( 0.09583mL) =0.0060M PH found = 2.98 [H3O+]=10-PH = 0.00105 M C9H8O4 + H2O C9H7O4 + H3O+ I 0.0060M 0M 0M C - 0.00105 +(0.00105) +0.00105 E 0.00495 0.00105 0.00105 Ka= [C9H7O4 ] [H3O+ ] /[ C9H8O4 ] =[(0.00105) (0.00105)] /( 0.00495 ) = 2.23*10-4 PKa = -log [ka] = 3.65 TLC: The thin layer chromatography used in part c) to confirm the purity of the five of the compounds written below; ______________________ ______________________ CS crude salicylic acid PS pure salicylic acid CA crude acetylsalicylic acid PA pure acetylsalicylic acid M methyl salicylate acid Retention Index Calculations; Rf= (distance travelled by spot) / (distance travelled by solvent front) Rf CS=1.5/5.3 = 0.28 Rf PS=1/5.3 =0.19 RfCA=1.8/5.3 =0.34 Rf PA=1.2/5.3 =0.23 RfM= 1.9/5.3 = 0.36 As observed that he distance traveled by the spots CS ,CA and M is larger comparing to the distance travelled by PS and PA spots which confirmed the purity of the compounds that was obtained in part a and b of the experiment. Otherwise, the larger the distance a spot travelled the less polar the compound would be. Ferric Chloride Test: In part c of the third week of the lab the ferric chloride test was used to determine the presence of phenol in the compound. According to the data shown below that the phenol was contained in each of the crude and pure of salicylic acid, methyl salicylate acid and a little in pure aspirin. # of tubes used Compound test Observation 0 Blank solution(FeCl3 ) Gold 1 Crude salicylic acid Dark brown (black) 2 Pure salicylic acid Dark brown (black) 3 Crude aspirin Light gold 4 Pure aspirin Medium brown 5 Methyl salicylate acid Dark brown (black) 6 Phenol Moderate Gold ( close to blank colour) 7 Benzoic acid Light gold Results and Discussion The purpose of this experiment was to carry out a three short steps (multistep) synthesis of acetylsalicylic acid to determine the yield efficiency and the percentage of the theoretical and actual yield of the aspirin. The first part of the experiment was the hydrolysis of methyl salicylic acid to make salicylic acid. Methyl salicylate (0.04mole, 6.0864g) was reacted with (50mL) sodium hydroxide of 5 M, ester and (135mL) of 1 M of sulfuric acid as excess to increase the yield of the reaction. The acidity of the solution then was determined by dabbing the solution on litmus paper using glass rod. However, during the acidity process the temperature of the mixture was increased due to the addition of a (15mL) of sulfuric acid to the reaction mixture in order to precipitate the salicylate acid. The reaction mixture was placed in a (600mL) beaker of ice cold distilled water to lower the temperature of the solution. After that, the mass of the crude salicylic acid that obtained was 5.14g with yield of (84%). The melting point of the crude salicylic acid was determined as (151-163oC) whereas the literature value of the compound (159oC). The broad range of the crude melting point had confirmed the impurity of the compound. The crude salicylic acid was then isolated by Buchner funnel hot filtration and then purified by recrystallization. The mass pure salicylic acid was weighted to be 3.2g with small yield of 53%. While, the second percentage yield of pure salicylic acid that calculated in the second part of the experiment was 48%. These low percentage yield of pure salicylic acid indicates that there was some loss of the compound. The compound weight was lost through transferring it from beaker to watch glass and over the filtration process. The reaction can be improved by adding more excess sulfuric acid to get a higher percentage yield of the crystals. The melting point range of the pure salicylic acid that obtained was (158-160oC), within the literature value of the compound (159oC). This sharp range of the melting point indicated the purity of the crystal salicylic acid that was obtained. The total yields for pure salicylic acid that obtained in each of part a) and b) of the experiments was 51% which indicated that there was some error while preforming the synthesis of aspirin that cause losing of the mass of the purified compound such as weight of the starting materials was not accurate and mass spilled through the purification of salicylic acid. In the second part of the experiment, acetylsalicylic acid was formed by acetylate 2.9g of pure salicylic acid. The crude aspirin formed after a reaction occurred between (2.9g) crystal salicylic acid, a 4.93 mL acetic anhydride and sulfuric acid of (0.3 mL, 50oC, 15mintues) a reaction catalyze. The reaction mixture was placed in warm water bath of 400mL beaker for approximated 15mintues until the solution became homogenous. After that, the beaker was removed from the warm bath and covered with watchcases to cool at a room temperature of 25oC. A (50mL) of cold water was added to the crystals acetylsalicylic acid to dilute any leftover of acetic anhydride. The crystal acetylsalicylic acid was then isolated by vacuum filtration for about 5 minutes. The mass of the crude aspirin achieved was 3.3g with a high percentage yield of 113.8%. This high percentage yield indicated that the crude aspirin was impure and contained more water and insoluble substance in which in return contributed to that percentage. Likewise, another reason that explained this high yield percentage is that the product was wet when the mass was weighted .Another method which confirmed the impurity of the crude aspirin is the melting point determination. Melting point determination is a technique that used in laboratory using Fisher- John’s apparatus to prove the pure and impure substance. However, the melting point range of crude aspirin that obtained experimentally was (134-144oC) a difference of 10oC comparing to the compound literature value 136oC. The crude product then placed into 250mL beaker and covered with 10mL of water to apply a hot filtration. The hot plate removed the crude product placed in ice water bath to cool and form solid crystals lattice. After the crystallization of the product was completed formed, the crude product isolated and purified by vacuum filtration, rinsed with 50mL of cold distilled water to reduce the dissolved crystals. The pure aspirin was weighted to have a mass of 2.3 g and yield of 79%. This low yield percentage indicated that some of the mass of the pure aspirins was lost during the recrystallization and purification process when the crystals were transferred from a beaker to watch glass (to compute the mass). Also, some of the product splattered and then lost during the vacuum filtration. However, the melting point range of the pure aspirin that obtained was (136-138oC) that is in return within the determined literature value of 136oC. This low range of the pure acetylsalicylic acid confirmed the purity of the compound. Finally, after the purification of the pure acetylsalicylic acid (aspirin) the role that had been done in the third part of the experiment was to confirmed experimentally the purity of the aspirin and salicylic acid using three different techniques beside the melting point analysis that had done in each of part a) and c) of the experiment such ferric chloride test (FeCL3), thin layer chromatography TLC analysis and the PH meter. The first test that had done was TLC plate in which four test tubes were labelled and filled with a small scapula tipful of each of the five compounds crude salicylic acid, pure salicylic, crude acid, acetylsalicylic acid, pure acetylsalicylic acid and methyl salicylate acid respectively. A (1mL) of methanol had been added to each of the four test tubes and then swirled each tube one at a time gently to obtain a homogenous solution. A TLC plate of 5 x 10 cm had been prepared by drawing a baseline about 10-15mm above the bottom of the plate and divided it into five line to spot each of five compound (CS, PS, CA, PA and M) on their hatchmarks. A developed chamber of (600mL) beaker of mixture of 50% ethyl acetate/50% hexane was prepared to run the TLC plate in it. A circle paper towel was placed at the bottom of the chamber to prevent the TLC plate from sliding while it developing. After the TLC developed and the solvent front reached the top of the plate, the TLC plate took out from the chamber and the solvent front distance travelled had been drawn using a pencil in order to obtain the retention index. Then, the spots of each of the five compounds were drawn and visualized under UV light. The purity of the aspirin and salicylic acid had confirmed as the Rf values of each of the compounds was calculated. The distance traveled of crude aspirin that determined was 0.34, while the distance that a pure aspirin travelled was 0.23. That illustrated, that crude aspirin was impure because it had larger distance travelled comparing the pure aspirin. As in aspirin, pure salicylic acid had the lowest distance travelled (0.19) comparing with the crude salicylic acid 0.28. However, the distance travelled of methyl salicylate acid was calculated to be 0.36 that explained the precipitation of the compound that observed in part a) of the experiment as it was acidify which means that methyl salicylate acid is insoluble and thus impure. Ferric chlorides test a second test technique that had used to determine the purity for each of acetylsalicylic acid, salicylic acid and methyl acetylate acid. Seven test tubes were clearly labelled from #1 to 7and then small amount a spatula-tipful of each of the sample (crude salicylic acid, pure salicylic acid, crude aspirin, pure aspirin, methyl salicylate acid, phenol and benzoic acid) were added to the seven tubes respectively. About 0.5mL (10 drops) of methanolic ferric chloride solution was added to each of the tubes and then swirled carefully to observe any colours changes. As soon as the ferric chloric was added the colour of each of the methyl salicylate acid and crude and pure of salicylic acid was changed to dark brown because of the hydroxide group. Otherwise, the change in the colour of these compounds indicated that phenol was existed. On the other hand, the color of the aspirin (light to moderate gold) was close to the blank color (gold) after the ferric chloride had been added to it which indicated and confirmed that the aspirin was completely pure from any un reacted salicylic acid and other compounds. The third and last methods that had been demonstrated in this experiment were the Pka. The acidity of each of the pure aspirin and salicylic acid were determined using PH scale. A mass of (0.1023g and 0.1035g) of each of salicylic acid and pure aspirin respectively had been weighted using analytic balance and placed separately in 250mL beaker. A 100 mL of distilled water added to each of the 250mL beaker and then the solutions of each of the beaker were stirred to obtain a clear homogenous mixture. The PH of the pure aspirin was determined (2.92) using digital PH meter which higher than the recovered literature value 2.4. While, the PH value of the pure salicylic acid that obtained experimentally was (2.59) that was also higher than the actual value of salicylic acid 2.4. However the pka value of aspirin 3.65 that was obtained from calculating the PH and the concentration (Ka) values. However, the Pka value of the pure salicylic acid that determined experimentally was 5.4 which concluded that pure aspirin is more acidic than pure salicylic acid. Otherwise, aspirin was a stronger acid than salicylic acid. Conclusions The meltsteps synthesis of acetylsalicylic acid had been used since the 18th centuries1. Aspirin had been used many years ago as a treatment for pain reliever1. However, in this experiment the hydrolysis of methyl salicylate acid used to make salicylic acid. Methyl salicylate acid was reached with sodium hydroxide of 5M and sulfuric acid 1M to yield a solid salicylic acid. A solid salicylic acid had been isolated and purified by vacuum filtration and recrystallization. After that, a reaction of purred salicylic acid of mass 2.9g had reacted with acetic anhydride and sulfuric acid at 50oc for 15 minutes to obtain aspirin. The purification of aspirin had determined using different techniques such Pka, melting point, TLC ferric chloride and recrystallization. The yield of purified aspirin was 79% which is a good result. The reaction yield can be improved by maximizing the catalyst or increasing the amount of reactant to obtain a more product and thus having a good yield. References: Stephen Van Dulken (author) Inventing the 19th century, New York University Press, Washington Square, 2001, page 20 Peter Urben (editor) Bertherick’s Hardbook of Reactive Chemical Hazards, 7th ed., Academic Press, 2006 Soloway, S., Wilen, S. H. Improved Ferric Chloride Test for Phenols, Analytical Chemistry, 1952, 24(6), page 979-983. The 92st edition of the CRC Handbook of Chemistry and Physics, 2011-2012 Neil, M.J. ( editor) The Merck Index, Merck & CO.,INK , 14th ed., Whitehouse stations, NJ, USA,2006, 11,15,20.