Jeana Greaves Chem3301-112 June 19, 2013 Synthesis of Aspirin from Methyl Salicylate Introduction The synthesis of Aspirin (Acetyl Salicyclic Acid) began with methyl salicylate and sodium hydroxide as the reagent. The polar oxygen accepts the electrons from now positively charged hydrogen. The positively charged sodium disassociates leaving the hydroxide ion with a negative Scheme 1 shows the mechanisms that were demonstrated during the synthesis of Aspirin. charge that attracts to the positively charged hydrogen.
A more stable structure is formed when the charge on the oxygen moves from being a lone pair to forming a double bond and the ether substituents are removed. In the presence of Hydronium, the negatively charged oxygen shares electrons with a hydrogen from the reagents. This mechanism allows for the formation of Salicylic Acid. When Acetic Anhydride is used as a reagent, the double bond on the ketone is transferred as a charge to the oxygen causing the opposite charges to attract. Once again, the electrophilic oxygen takes the lone pairs between the O-H bonds to form the final product of Aspirin and acetic acid.
These mechanisms for this experiment can be seen in Scheme 1. Aspirin is classified as a Non-Steroidal Anti-Inflammatory Drug that is indicated for heart attack, pain, and fever. Greaves 2 Procedures Part A: Ten milliliters of 6M Sodium Hydroxide was added to two milliliters of methyl salicylate in a test tube. A white, crystal-like precipitate was immediately formed. Even upon shaking, the solution held its structure. The test tube was placed in a water bath containing boiling chips for while swirling the contents occasionally. The test tube was removed after 20 minutes.
The precipitate no longer remained; the solution was now a pink liquid. The contents of the test tube were poured into a beaker to cool for approximately five minutes. Once cooled, 25 milliliters of 6M Hydrochloric Acid were slowly poured into the beaker. Precipitation occurred leaving a white powder-like substance in the beaker. This beaker was placed in an ice bath until a clear separation of layers was clearly seen. Upon removal of the beaker from the ice bath, a pH strip was hovered above the solution were the strip changed color to a red-shade which indicated a pH of approximately two.
Vacuum filtration was assembled in order to isolate the white precipitant—Salicyclic Acid. Cold, deionized water was used to ensure that all of the visible precipitant was transferred from the beaker to the filter paper. The substance underwent vacuum filtration for five minutes then placed onto a paper towel in order to dry. The precipitate weighed 3. 90 grams. A capillary tube was used to collect a small sample of the powder. The sample was used to determine a crude melting point of 145 °C. The specimen was placed in a desiccant jar and allowed tofurther dry for 72 hours.
Part B: Once dried, the specimen was measured as 1. 83 grams. One gram was isolated for further testing and placed into a test tube. Two milliliters of Acetate Anhydride and five drops of concentrated Sulfuric Acid was added to the test tube and shaken vigorously. Only a small amount of the powder remained; the addition dissolved the specimen; a pink liquid was formed. The test tube was placed in a warm water bath (51°C) until no powder could be observed. After nineteen minutes, the test tube was removed.
The solution was transferred to twenty milliliters of cold, deionized water which resulted in the precipitation of a white substance—Aspirin after six minutes of cooling. The contents of the beaker underwent vacuum filtration in order isolate the precipitant. Once the vacuum crudely dried the powder, the filter paper and contents of the Buchner Funnel where placed on a paper towel to further removal of water while the aqueous layer within the filter flash was discarded in the liquid waste container. A small sample was captured in a capillary tube to determine an approximate melting point.
When the melting point was deterred as 79°C, further purification of the substance was 2 Greaves 3 required. The specimen was returned to a test tube with deionized water and placed in a boiling water bath. Once the powder was no longer visible, the test tube was transferred to an ice water bath where the crystals reformed. Once again, the specimen was filtered with vacuum system, dried on a paper towel, and tested to determine a crude melting point. The synthesized Aspirin was determined to have a crude melting point of 132°C.
Calculations and Results Formula1 shows the conversion of milliliters of methyl salcyclate into grams of methyl salcyclate. Formula 2 used the molar ratio of Salicyclic acid to Methyl Salicylate to determine the theoretical amount of Salicyclic Acid mols. Formula 3 converts the product of the experiment A into grams. Formula 4 determines the percent yield. Formula 5 was used in Table 1 to determine percent errors of the crude melting points. The percent error of Salicyclic Acid was determined to be 53%. 3 Greaves 4 The experimental melting points (MP) were compared in table 1 to the accepted values.
Both percent error values where under 10%. Table 1 charts the melting points of the compounds used within the lab. Compound Salicyclic Acid Aspirin Actual MP (°C) 158. 6 139 Experimental MP (°C) 145 132 Percent Error (%) 8. 3% 5. 0% Discussion The dissociation of Sodium Hydroxide provides a basic environment where methyl salicylate becomes deprotonated as seen in the first reaction of figure 1. The hydrochloric acid is added to the solution to react with water yielding a highly concentrated environment of positively charged hydronium ions.
The charged oxygen removed a proton (hydrogen) from the hydronium in order to produce Salicylic Acid. Similarly, the Sulfuric Acid is used to protonate the oxygen of the Acetic Anhydride. The nucleophilic addition reaction between the salicylic acid and the charged Acetic Anhydride yields an intermediate before nucleophilic elimination occurs yielding a final product of Aspirin. Such a large percent error of the Salicyclic Acid indicates that the Methyl Salicylate was not 100% pure. A proper measurement of the dilution of the solution could be accounted for within Formula 1.
Both the sample of the Salicyclic Acid and Aspirin were wet when the melting points were determined. The water contained with the samples was possibly the result of the skewed measurements. Conclusion The synthesis of Aspirin demonstrated key concepts of organic chemistry. Oxygen is a highly nucleophilic which resulted in the acceptance of protons throughout the synthesis. However, oxygen acted as electrophile in the transformation of hydronium into water in order to terminate the positive charge as seen between the third and fourth step of Figure 1.