Digitally signed by Jason Raquin Roque DN: cn=Jason Raquin Roque, o, ou, email=jason_mike15@yahoo.com, c=PH Date: 2012.05.

15 14:24:03 +08'00'

Synthesis of Aspirin and Oil of Wintergreen

Roque, Jason R. Frias, Abigail Pauline F. De Ramos, Jason Jalou Bachelor of Science in Biology Major in Human Biology College of Science De La Salle University Dasmarias Dasmarias, Cavite, Philippines

ABSTRACT

The foremost objective of this experiment was to formulate an aspirin. This is the combination of the salicylic acid and acetic anhydride thus forming the Aspirin also known as the Acetylsalicyclic Acid. With about 1.104 g of salicyclic acid was mixed comprehensively with 3 drops of 85% Phosphoric Acid and 2.4 mL acetic anhydride. It was placed in a water bath with a constant temperature of 90C for 5 minutes. Then a 1.0 mL of water was added to the mixed reagent and then placed in a room temperature condition to facilitate the Aspirin crystallization. After 10 minutes, the mixed reagents have been filtered using a vacuum filtration for it to separate the impurities in the Aspirin. Then the Actual yield was determined with the use of Analytical balance a modern technology used in measuring mass with precision. Through the use of the Analytical results and the theoretical results the percent yield of the synthesize Aspirin was obtained. Melting point was also determined in order to make sure that the percentage yield is accurate. Aspirins o percentage was 9.64%. On contrary, the melting point of the aspirin is 130 C. Based on the gathered results the formation of the Aspirin have gave an accurate outcome base on the true value of the Melting point of the Aspirin which is between 132C-137C. It can be hypothesize that the Aspirin made is a successful one.

INTRODUCTION

Aspirin (also known as acetylsalicylic acid) is in a group of drugs called salicylates. It works by reducing substances in the body that cause pain, fever, and inflammation. It is also known to treat mild to moderate pain, and also to reduce fever or inflammation. It is sometimes used to treat or prevent heart attacks, strokes, and angina. On the other hand, the oil of wintergreen or methylsalicylate also came from the same active ingredient, salicylic acid. Commercially, it is used as a flavoring for candies and chewing gum and in the treatment of muscular aches and pains. When synthesized and sold as the oil of wintergreen itself, it can be sold as beverage. The two compounds indicated are both organic esters. An ester is a compound that is formed when an acid (containing the COOH group) reacts with an alcohol (a compound containing an -OH group). In this experiment the experimenters will prepare two esters of o-hydroxybenzoic acid, more commonly known as salicylic acid. One of the esters, acetylsalicylic acid, is aspirin, the common analgesic. They will synthesize aspirin by mixing salicylic acid with acetic anhydride. The second ester product is oil of wintergreen, or methylsalicylate, which we prepare by allowing salicylic acid to react with

methyl alcohol. This compound, which has a familiar odor, is used as a flavoring agent and in rubbing ointments.

HO

O OH H3C O CH3

HO

O O O CH3

H+

+
O O

H3C

OH

Figure 1. Salicylic acid and acetic anhydride reacts to form acetylsalicylic acid and acetic acid

HO

O H3C OH

O H OH O H

H+

H3C

OH

Figure 2. Salicylic acid and methanol reacts to form methylsalicylate.

This experiment illustrates several properties of organic synthesis. While both product compounds in the experiment are esters of the same compound (salicylic acid), they are quite different in structure. Aspirin involves a reaction of the -OH group of salicylic acid, while methyl salicylate involves a reaction of the -COOH group of salicylic acid.

MATERIALS / REAGENTS & EXPERIMENTAL PROCEDURE

On making aspirin, he experimenters prepared a water bath that is heated in a temperature between 70-90 degrees Celsius. While heating, they prepared a salicylic acid with weigh approximately 0.150g. In a dry clean test tube, they mixed the acid with 85% H2SO4 solution and 0.3 mL acetic anhydride. They heated the reaction mixture in a water bath until the salicylic acid is dissolved and colorless. They added ice to the mixture for recrystallization. The aspirin is collected by filtering in the Buchner funnel and through washing with cold water. The aspirin was then dried overnight and weighed again for data collecting. On making methylsalicylate or oil of wintergreen, the experimenters prepared a salicylic acid with weigh approximately 0.25g. In a dry clean test tube, 2.0 mL methanol was added and mixed until the salicylic acid is dissolved. They carefully added 10 drops of concentrated H2SO4 and placed the mixture in a water bath (heated) for 15 minutes and cooled the mixture in running water afterwards. The odor of the product is then observed. On performing the FeCl3 test, the collected products were now separated in each test tube. The aspirin was dissolved first with 5 mL of distilled water. Each test tube was added with 1 drop of 1% FeCl3 and their reactions was now observed.

DATA & RESULTS The table below shows the percentage of aspirin which is 9.64%, it shows that the experiment was then successful in producing almost the same amount of the sample needed.

Table 1. Percentage Yield of the Aspirin Yield of Aspirin Mass of Salicylic Acid 0.1516 g Mass of Acetyl Salicylic Acid 1.6400 g % Yield 9.64%

In this reaction, acetic anhydride and salicylic acid is reacted under high temperatures. However, simply increasing the reaction temperature isnt enough. A catalyst is also needed as salicylic acid is stabilized by its benzene ring, with lone pairs from the carbonyl group and the hydroxyl group delocalizing with the electrons of the aromatic ring. In this case, we utilized sulfuric acid (H2SO4) as the reaction catalyst. While the reaction proceeded, the color of the reaction mixture changed from white to colorless. This was due to the increased heat, which increased solubility and allowed the white salicylic acid crystals to dissolve, forming a colorless mixture. Also, acetylsalicylic acid is much more soluble in water than salicylic acid, though both exist as white crystals. Thus, the disappearance of the color white in the reaction also meant that more soluble acetylsalicylic acid crystals which could dissolve were being formed, and that relatively insoluble salicylic acid crystals which couldnt dissolve were being used up. Only when there action started to cool down did white crystals of acetylsalicylic acid form, as solubility gradually dropped with the reduction in temperature. After the formation of crystals, 0.2 mL of cold deionized water was added. This was to get rid of the acetic acid by-product, either by dissociation and filtration, or by decomposition. The presence of acetic acid in the product would reduce purity and erroneously increase our yield. Furthermore, acetic acid can theoretically react with our product, leading to the production of more unwanted by-products. The water added to get rid of the acetic acid and to wash the crystals must be cold as acetylsalicylic acid is soluble in water. The reduced temperature would help to lower the solubility of our product in water, and therefore lower the amount of product lost via dissociation and filtration. Also, water can decompose our product back to salicylic acid and acetic acid via autocatalytic degradation. Using cold water instead of warm or hot water would greatly reduce such a possibility. After obtaining the white crystals of product, they were then recrystallized with a mixed solvent system of ethanol and water. In this case, a mixture of 2 solvents (solvent-pair) is much more satisfactory than a single solvent. This is because ethanol does not readily dissolve our product, unlike water. If only ethanol is used in recrystallization, very large amounts of ethanol would be needed in order to completely dissolve the crystals. On the other hand, if only water is used in recrystallization, the crystals can be completely

dissolved in a very small amount of solvent, making recrystallization difficult as the product will still being solution even after much boiling and solvent evaporation. Thus, in order to get the best of both worlds, a mixed solvent system should be used. After recrystallization, filtration and drying, our product yield was a mere 9.64%. However, after referring to several similar experiments carried out by others, I come to the conclusion that this is a rather low-yield reaction, and a yield that is larger than 60% is rather reasonable. Yields of up to 90% will rarely, if ever, be reached. The derived melting point range for our product is between 124.5C to 126.8C. This is very far from the theoretical melting point of 135.0C. However, like the reaction yield, similar replicates of this experiment done by others have results that differ greatly from theoretical values. Reported melting point temperatures for acetylsalicylic acid in scientific literature vary from 125C to137C. Our melting point range is close to the reported melting point ranges of other researchers. However, it is far from the actual melting point. Thus, we can deduce that although it is the most commonly used reaction to synthesize acetylsalicylic acid, it does have its disadvantages, such as low yield and purity. The low yield and purity that we obtained in this experiment are not only attributed to the experimental procedure and mechanism, but also to other experimental flaws. The low yields could be due to several factors, such as disturbance during crystallization, incomplete reaction and overheating. After all, crystal formation is highly dependent on critical temperature and the level of disturbance the saturated solution is subjected to. Similar to previous experiments, the usage of filter paper containing paper pulp reduced experimental yields as some product was left behind in the Buchner funnel and on the filter paper after suction filtration. Some were also stuck amongst the fibers of the filter paper that we utilized. During the synthesis and recrystallization of acetylsalicylic acid, it is preferable to maintain the temperature at a fixed 90C. This is because studies carried out have determined that this is the critical temperature for acetylsalicylic acid crystal formation. At this temperature, the formation of acetylsalicylic acid crystals is at its optimum. Maintaining a certain temperature is almost impossible when dealing with an oil bath on a hot plate. Thus, more advanced heating technology could be utilized, such as heating mantles and heat controllers. Even the common water bath can be used. Unlike the hot plate, the temperature of a water bath is not prone to fluctuations, and a water bath provides us with the exact temperature of the water it contains, unlike a hotplate. Also, with current experimental procedures it is difficult to determine whether the reaction has reached full completion. A trace amount of salicylic acid and acetic anhydride might still be present in the reaction mixture. There is a method to detect for the presence of phenols such as salicylic acid, the only phenol in this reaction. Iron (III) chloride (FeCl3) reacts with phenols to form brightly colored complexes that range from violet to red. Thus, it provides us with an easy method to test for the presence of unreacted salicylic acid. After the reaction is refluxed, 3 test tubes are labeled 1 through 3. 5 mL of distilled water is placed in each tube. A few milligrams of pure salicylic acid are then added to tube 1. Next, a few milligrams of pure acetylsalicylic acid is added to tube 2. A few milligrams of commercial aspirin were added to the last test tube. All tubes are shaken to dissolve the crystals within, and 1 drop of 1% FeCl3 is added to each of the 3 tubes. If the reaction is complete, we would expect tube 1s contents to react and change color, while the other 2 tubes remain unreacted.

REFERENCE (1) Legaspi, G. A. & Sta. Ana, S.T. 2010. Essentials of Organic Chemistry Laboratory (2) Retrieved at March 14, 2011 from http://www.britannica.com/EBchecked/topic/426191/oil-ofwintergreen (3) Retrieved on March 14, 2011 from http://science.csustan.edu/nhuy/chem1002/aspirin.htm (4) Retrieved on March 15, 2011 from http://www.reachoutmichigan.org/funexperiments/quick/csustan/aspirin.htm (5) Retrieved on March 15, 2011 from http://www.aspirin-foundation.com/cardio2.htm