In 1897 Felix Hoffman (Fig. 2), a German chemist, was working for the Bayer chemical company. Hoffman desperately needed to devise a less acidic pain reliever as his father could consume for his arthritis. His researches resulted in the synthesis of acetylsalicylic acid (ASA) or aspirin. Bayer patented the name and commenced to market the product in 1899. It was a great success and sales rose rapidly. In fact, the company set up by Friedrich Bayer & Company is generally considered to have been the first pharmaceutical company, and the production of aspirin has beyond a shadow of a doubt laid the foundation to the modern pharmaceutical industry (Aspirin Foundation, 23 May 2010).
Figure 2: Baeyer Hoffman (Wikipedia 2004).
Only till 1970’s, scientists begins to grasp the understanding on how aspirin act as a pain reliever. Today 80 billion aspirin tablets are consume every year over the across the globe to reduce fevers, alleviate pain, and even keep heart attacks at bay. Bayer In commercial aspirin products, a small amount of ASA (300 to 400 mg) is held together with a starch binder and sometimes caffeine and buffers to make an aspirin tablet. The basic conditions in the small intestine break down the ASA to yield salicylic acid, which is absorbed into the bloodstream. The addition of a buffer reduces the irritation caused by the carboxylic acid group of the aspirin molecule (Aspirin Foundation, 23 May 2010).
3. Theory
The reaction below as shown in figure 3 is also known as esterification. It is a condensation reaction, whereby two molecules combine to form one single molecule, while removing a small molecule (e.g. H2O) in the process (Manju Mehta & Bhupinder Mehta 2006).
Esters are organic compounds with the general formula RCOOR’, where R and R’ can be an alkyl group or an aromatic group. Alkyl group is an alkane that is with one less hydrogen atom since it needs one bond to be branched from the parent chain. Aromatic compounds are a class of molecules containing benzene, a six-membered carbon rings with delocalized pi electrons. This type of group is found in salicyclic acid and ASA (Manju Mehta & Bhupinder Mehta 2006).
Esters are readily synthesized by the reaction between a carboxylic acid, RCOOH, and an alcohol, R’OH, as shown in the following reaction (Fig. 3).
Figure 3: Esterification Process (Prentice-Hall of India Private Limited 2006).
The reaction to I have used synthesis ASA is very similar to the one above. Salicylic acid a phenol consisting of a phenyl bonded to the hydroxyl (-OH) which is very much alike to alcohol and acetic
Anhydride is a dehydrated carboxylic acid (acetic acid). We use concentrated sulphuric acid as the catalyst. After the warm bath to complete the reaction, we added cold water to quench the reaction (hydrolysis of acetic anhydride) to prevent further reaction to take place. The cold water must be added quickly as to allow fast crystal formations due to the drastic drop in temperature. Stir and rub the walls can create uneven surfaces hence inducing crystallization (Manju Mehta & Bhupinder Mehta 2006).
As such, in this experiment, 2.4 grams of salicylic acid should yield 3.13 grams of Aspirin, it is stated that acetic anhydride is in excess. This is proven by the following calculation:
Mol of salicylic acid in this experiment:
2.4(2d.p)/138 = 0.0174 (3 significant figures)
Mol of salicylic acid: Mol of Aspirin
1 : 1
Therefore, Mol of Aspirin:
0.0174/1 x 1 = 0.0174 (3 significant figures)
Expected mass of Aspirin:
0.017391 x 180 = 3.130 (3 decimal places)
The solid ASA formed contains impurities and should be recrystallised to achieve a purer state. Recrystallization is possible because most solids are more soluble in hot solvents than in cold solvents. The solubility of ASA increases as temperature increases. This means that if aspirin is dissolved in ethanol to produce a saturated solution and that solution is cooled, the aspirin will crystallize during the cooling (Addison Ault 1998).
Ethanol has been chosen as the solvent because the polar nature of the hydroxyl group causes ethanol to dissolve many ionic compounds, moreover the ethanol molecule also has a non-polar end, and it will also dissolve non-polar substances (Addison Ault 1998).
While cooling, crystallization takes place. In crystallization, there is a slow, selective formation of the crystal framework resulting in a pure compound. Instead in precipitation, due to the rapid formation it will trap impurities in the solid’s crystal framework. For this reason, we should include crystallization to get a purer solid substance (Addison Ault 1998).
The alternate way of synthesizing the aspirin (Fig. 4) can be produced by replacing the acetylating agent from acetic anhydride to an even more acidic acid known as acetyl chloride CH3COCl. This can increase the percentage yield of ASA, since acetyl chloride is more acidic. The reaction of acetyl chloride with salicylic acid is showed below. However, the by-product is hydrochloric acid (HCl) instead of acetic acid (Addison Ault 1998).
Figure 4: Alternative for aspirin production (Earlham 2003).
However, Acetic anhydride is preferred because it is less hazardous to use and less expensive than acetyl chloride. In industry, the acetic acid produced in this reaction can be recovered and converted back into an essential initial product(acetic anhydride) by the process known as dehydration as seen in Fig. 5. With the aid of dehydration reaction, industries may save a significant amount of money from purchasing acetic anhydride from other companies (Manju Mehta & Bhupinder Mehta 2006).
Figure 5: Dehydration (Chemguide 2004).
We may also create Salicylic acid from Kolbe’s reaction (Fig. 6) whereby we initiate the reaction with the starting product of phenol. Salicylic acid is less available in market as compared to phenol hence it is important for us to know how to derive salicylic acid from phenol.
Figure 6: Kolbe-Schmitt Reaction (Wikimedia 2006).
4. Procedure
Precipitation:
Foremost, approximately 2.4 grams of salicylic acid was weighed and placed in a dry, 100ml conical flask. Next, 6ml of acetic anhydride was added into the same conical flask, along with 3-4 drops of concentrated H2SO4 as catalyst. The conical flask was then heated at 80-100 degree C in a water bath for 10 to 15 minutes to hasten the reaction. Immediately, 1ml of distilled H2O was added into the conical flask after it was removed from water bath. Additionally, 40ml of cold distilled H2O was added to the conical flask. Furthermore, a stirring rod was used to gently ‘rub’ against the side of the conical flask to induce crystallisation. Without further delay; Suction filtration was then carried out to remove the crystals from the solution. Subsequently, the crystals were removed from the filter paper. To ensure accuracy, cold distilled H2O was used to wash away remaining crystals from the filter paper.
Recrystallisation:
First of all, to recrystallise the solids, the solids has been dissolved in 5ml of ethanol. Followed by that, 30ml of hot; distilled H2O was added into the solution, and slowly cooled. Gradually, crystallisation of Aspirin took place as the solution was cooled to room temperature. Afterwards, suction filtration was performed to remove the Aspirin from the solution. Subsequently, the residue was then placed on a watch glass along with the filter paper. Later on, aspirin was dried by placing it in the oven for 20 minutes, along with the watch glass and filter paper. Immediately, it was transferred to the desiccators for 15 minutes as it was dried further. Finally, the crystals remained on the filter paper are pure, dry, Aspirin.
Melting Point Determination:
After obtaining Aspirin, the melting point of Aspirin has been determined using the capillary method.
5. Results and Calculation
Mass
Mass of salicylic acid (a) = 2.39 g
Mass of filter paper & watch glass (b) = 33.11 g
Mass of dried, recrystallised aspirin, filter paper & watch glass (c) = 34.64 g
Mass of dried, recrystallised aspirin (d) = (c) - (b)
= 34.64-33.11
= 1.53 g
Percent yield
Number of moles of salicylic acid used (e) = 0.0173 mol
(Molecular weight of salicylic acid = 138)
Expected number of moles of aspirin (f) = 0.0173 mol
Expected mass of aspirin (g) = 3.12 g
(Molecular weight = 180)
Melting point
Temperature range 137.9-140.5 oC
Appearance
Needle shaped, white, and shiny.
6. Discussion
My percentage yield ASA is relatively low since it is only 49%. This may occur due to several factors:
While salicylic acid has been transferred, some of the solids may have retained by the side of the conical flask and even on the spatula, and resulted in lesser salicylic acid participating in the process of esterification compared to what have been weighed earlier. Thus, this had resulted in lower yield of the crystal ASA. It is advisable to wash the walls with distilled water to ensure more salicylic acid will participate in the reaction (Manju Mehta & Bhupinder Mehta 2006).
The initial amount of salicylic acid was dissolved in the solution of acetic anhydride and concentrated sulphuric acid, it has not completely dissolved into the solution, even when it was heated. This could have a slight impact on the results of the overall yield of aspirin because it was possible that not all of the salicylic acid was synthesized. To determine if this affected the synthesis of aspirin at all, the experiment should have been ran a second time to see if the same thing occurred. The iron (III) chloride test also could have been ran to determine if any of the aspirin degraded to salicylic acid or never converted from salicylic acid (Manju Mehta & Bhupinder Mehta 2006).
During the suction filtration we should rinse the solid ASA formed in the conical flask and the glass rod during the synthesis before pouring into the Buchner funnel repeatedly. After the final suction filtration, another error causes the percentage yield to drop. This is due to the crystals not being fully collected on the filter paper, but rather, remains on the side of the Buchner funnel. This loss can be minimized by the crystals from the side of the Buchner funnel to the filter paper moving using a metal spatula before collecting the filter paper and placing it on the watch glass (Manju Mehta & Bhupinder Mehta 2006).
During recrystallization, one common error of adding too much solvent (ethanol) will result in less percentage yield while cooling. We should refrain from moving or shifting the solution while it is cooling as it will interrupt the crystal formation since the particles are generally held by weak dispersion forces, dipole-dipole forces, and hydrogen bond. We should also allow slow crystal formation as fast crystal formation will cause the trap of impurities and giving higher percentage yield (Manju Mehta & Bhupinder Mehta 2006).
With the presence of impurities the melting point will decrease and vary in a larger range.
7. Conclusion
In conclusion, the experiment is a success since I have managed to synthesis and recrystallise the ASA although we have relatively low percentage yield of 49% that may arise due to several factors as stated in the discussion. I was able to analysis the melting point of the recrystallised aspirin and it is generally low in temperature which implies the presence of impurities.
8. Reccomendation
The experiment may be improved by changing the acetylating agent from acetic anhydride to acetic chloride. It will increase the percentage yield of aspirin and increase the chance of fulfilling the aim of synthesising aspirin.
The experiment may also be improved by increasing number of recrystallisation process to give a purer product. A purer product will give a narrow range of melting point and closer to the desired melting point of approximately 135 degree Celsius.
Furthermore, we ought to be quick when transferring the aspirin from oven to desiccators because during phase of time, water may condense on the aspirin and we may attain greater weight. This may give rise to a higher calculation of percentage yield as compared to the actual percentage yield.
When using glass rod to rub against the walls of the conical flask to induce recrystallisation, extra caution should be observed as the glassware is rather fragile. Students conducting the experiment should put on our gloves and safety goggle at all times because we will be dealing with corrosive acids such as sulphuric acid and acetic anhydride. Moreover, acetic anhydride will quickly blister skin if not washed off, when acid anhydride is in contact with our skin, we have to wash off with water and finally with dilute ammonia solution. Lastly, we should never pour concentrated acid to water as the water will boil and cause acid to spatter. Instead, we should only pour water to acid.
8. References
Internet:
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Aspirin Foundation, 2008. The Synthesis of Aspirin [online]. Available from: [Accessed 23 May 2010].
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Chemistry Zone, 2010. How to prepare Oil of Wintergreen [online]. Available from: [Accessed 24 May 2010].
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DSC, 2010. Synthesis of Aspirin & Oil of Wintergreen [online]. Available from: [Accessed 24 May 2010].
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Earlham College, 2003. Synthesis of Aspirin [online]. Available from: [Accessed 24 May 2010].
Books:
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Addison Ault, 1998. Techniques and Experiments for Organic Chemistry. 6 ed. USA: University Science Books.
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Manju Mehta and Bhupinder Mehta, 2006. Organic Chemistry. New Delhi: Prentice-Hall of India Private Limited.
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