Introduction: The purpose of this lab was to demonstrate the ability to easily alter the molecular structure of a compound to greatly increase its utility. In this case, an acetyl group was added to salicylic acid, a naturally occurring compound with significant pharmaceutical value. Without the addition of the acetyl group, salicylic acid is an irritant to the gastro-intestinal (GI) tract. Once the acetyl group is added via a simple reaction, acetylsalicylic acid (commonly referred to as aspirin) is formed.
Aspirin does not have the same negative effect on the GI tract as salicylic acid and has shown itself to be not only one of the safest and most effective analgesics, but vital in the prevention of heart attacks and strokes in those with history of these conditions or otherwise predisposed to them. This lab facilitated an in depth look at both acid-catalyzed and base-catalyzed reactions to produce aspirin from salicylic acid and the critical differences between the two.
The lab demonstrated both the simplicity of the overall reaction, but also a number of considerations regarding the final come which will be discussed in great detail below. The process of the lab included two acid-catalyzed reactions (using BF3(MeOH) and H2SO4). , and two catalyzed with bases (anhydrous sodium and pyridine). Salicylic acid was combined with acetic anhydride in four test tubes, and one of the four catalysts was added to each. The reactions were monitored and timed to track their rates, and then all four test tubes were combined, washed in water solution, and the aspirin produced was massed.
Equation Used: % Yield = Mass of Products (g)/Expected Mass (g) X 100% (equation 1) Results: Structures: The following compounds and their structures were used in this experiment (figure 1; figure2; figure 3; figure4; figure5; figure6; figure7): Reaction Mechanisms: Figure 8. Un-catalyzed production of aspirin Step 1 Step 2 Step 3 Figure 9. Acid-Catalyzed production of aspirin Figure 10. Base-Catalyzed production of aspirin Data: Table 1: Catalyst| Acid/Base role played| Time (in sec. )| 1g Anhydrous sodium acetate| Base| 120| 3 drops pyridine| Base| 35|
3 drops BF3(MeOH)| Acid (Lewis)| 6| 3 drops H2SO4| Acid| 23| Table 1 shows the four catalysts used in the experiment, the role they played in the formation of acetylsalicylic acid, the duration of time in which the temperature of the reactants rose by 4 °C (signaling the rate of the reaction). Table 2. Masses taken during the experiment (in grams) Reagent| Total mass| grams/mole| Moles| Salicylic acid| 2. 023g| 138. 121| 0. 014646578| Acetic Anhydride| 4. 32g| 102. 089| 0. 042316018| Product| Total mass| grams/mole| Moles| Acetylsalicylic acid| 0.
133g| 180. 157| 0. 000738| Calculations: Mass of Salicylic acid: (test tube 1) +(test tube 2) + (test tube 3) + (test tube 4) = Total mass 0. 507g + 0. 508g + 0. 506g + 0. 502g =2. 023g Mass of Salicylic acid= 2. 023g (see table 2 above) Mass of Acetic Anhydride: Convert 1ml of acetic anhydride to grams: 1ml of acetic anhydride X 1. 08g/ml = 1. 08g (test tube 1) +(test tube 2) + (test tube 3) + (test tube 4) = Total mass 1. 08g + 1. 08g + 1. 08g + 1. 08g = 4. 32 (see table 2 above) .
Conversion to moles: 2. 023g of Salicylic acid / (138. 121g/mol) = 0. 0146 moles 4. 33g of Acetic anhydride / (102. 089g/mol) = 0. 042 moles.
Acetylsalicylic acid expected ————————————————- % Yield = Mass of Products/Expected Mass X 100% 0. 133g (from table 2) /2. 64g X 100% = 5. 04% % Yield| 5. 04%| Table 2. % Yield Discussion: The un-catalyzed mechanism for the synthesis of aspirin (not conducted in this experiment) involved the nucleophilic attack of the alcohol group on the salicylic acid molecule on one of the carbon atoms double bonded to an oxygen in acetic anhydride (step 1), forming a bond between the oxygen in the alcohol group and the carbon atom in acetic anhydride.
This attack caused the oxygen atom of the alcohol group on the salicylic acid molecule to incur a positive charge and the electrons forming the pi bond between this carbon and oxyen on the acetic anhydride molecule to shift to the oxygen atom to become a lone pair (giving the oxygen atom a negative charge). At this point, the alcohol group on the salicylic acid molecule that conducted the electrophilic attach was deprotonated (step 2) due to the fact that oxygen, being a relatively highly electronegative atom is unstable with a positive charge.
In the 3rd step, the oxygen atom, which incurred the negative charge after receiving he lone pair of electrons, shed those electrons to reform the pi bond with the vicinal carbon atom. Because this carbon atom would then exceed the octet rule, the bond it had with the other oxygen atom from the original acetic anhydride molecule was broken, releasing a carboxylic acid molecule as a leaving group.
As seen in this experiment, the rate of the reaction was increased by acid/base catalyzation. From the results of the experiment (table 1) the two acids, BF3(MeOH) and H2SO4, increased the rate of the reaction by a greater degree than the two bases (Anhydrous sodium and pyridine).
This makes sense upon examination of the two catalyzed reactions. In the case of acid-catalyzed synthesis of aspirin, the presence of the acid caused the protonation the oxygen atoms double bonded to a carbon in acetic anhydride (step one), which in turn caused the pi bond it shares with the carbon atom to shift to the electronegative oxygen atom to free itself of the positive charge incurred by protonation. This had the effect of creating a carbocation, which increased the electophilicty of the carbon atom and the likelihood of and attack from the nucleophilic oxygen atom of the alcohol group on the salicylic acid molecule (step two).
The rest of the acid-catalyzed reaction proceeded in a similar fashion to the un-catalyzed version. In the case of base-catalyzed synthesis of aspirin, the presence of the base caused the deprotonation of the oxygen atom of the alcohol group on the salicylic acid molecule, giving it a negative charge and increasing it’s nucleophilicity and hence the likelihood that it will attack an electrophilic carbon atom double-bonded to an oxygen atom in acetic anhydride.
As with the acid-catalyzed reaction, this reaction proceeded in a similar fashion to the un-catalyzed version. Error As shown in the results, the percent yield of the reaction was 5. 04%. This small percentage could possibly be explained by the presence of unintended by-products. Much of the reaction depended on specific nucleophiles (in this case, the oxygen atom of the alcohol group on the salicylic acid molecule) attacking specific electrophiles (the carbon atoms double bonded to an oxygen in acetic anhydride).
If any other reactions occurred in the test tubes other than what was specifically intended for the synthesis of aspirin, these potential by products, which may or may not have been soluble in water, could have remained in solution once he aspirin which precipitated was separated. Another source of error could have been insufficient reaction times or cooling, which allowed the aspirin to precipitate. In either of these cases, the mass of aspirin collected would be lower than expected.