Hydrolysis of Methylsalicylate for the synthesis of acetylsalicylic acid
Abstract
The aim of the experiment “ Hydrolysis of Methyl salicylate for the synthesis of acetylsalicylic acid” is to produce aspirin with an optimized level of purity. The experiment is composed of two parts, the hydrolysis of methylsalicylate which is also known as oil of wintergreen is used to produce salicylic acid (part 1) and the made salicylic acid is then used to prepare acetylsalic acid which is the aspirin (part 2). A second purification procedure is followed through recrystalization of the aspirin in order to obtain the best results. As a result 1.72g of pure aspirin is obtained with an unsatisfying yield of 19 per cent.
Introduction
Brief review of previous researches on aspirin
The begin of the creation of aspirin goes back to 400 BCT (Bayer Healthcare LLC, 2009). The Greek physician Hippocrates found out that salicin, which was derived from willow bark and leaves, can relieve pain and fever. In 1832 a German scientist discovered the creation of salicylic acid. The salicylic acid has as asperin anti-inflammatory,
Aspirin can relief various kinds of pains such as fever rheumatism, lumbago and neuralgia (Bayer Healthcare LLC, 2009). It was even found that aspirin can prevent strokes and heart attacks for men. Aspirin is nowadays the most popular drug all over the world. This was one of the reasons why the synthesis of aspirin was undertaken since it is useful for students, intending to work in the medical health field, to gain some insight into the synthesis of this drug. In this research paper the following hypothesis will be tested:
HO: The amount of salicylic acid initially used is not equal to the amount of aspirin synthesized.
H1: The amount of salicylic acid initially used is equal to the amount of aspirin synthesis.
Theory
Overview over the two main reactions taking place
Two main reactions took place. First of all salycylic acid was synthesised from methylsalicylate which is also known as wintergreen. Afterwards salicylic acid reacted with acetic acid and acetylsalicylic acid was produced in an esterification process.
Saponification of oil of wintergreen
The first step of the reaction is the saponification of oil of wintergreen. Saponification is a special type of hydrolysis which is referring to the conversion of an ester into their corresponding alcohol and carboxylic acid. By a saponification methylsalicylate is converted to salicylic acid, by firstly heating the oil of wintergreen in a solution of sodium hydroxide up. By boiling the solution the necessary activation energy is provided which is needed for the reaction to take place. The following chemical reaction took place:
Na +
Sulfuric acid is added in order to obtain salicylic acid. In this acidification step the carboxylic acid group is protonated. The following reaction occurs:
Sufficient sulfuric acid is added to ensure that the salicylate ion is protonized. To asses whether sufficient amount of sulfuric acid was added it was checked whether pH<3.
Aspirin synthesis
Aspirin can be synthesized by an esterification process with of salicylic acid reacting with acetic acid or acetic anhydride. Esterification refers to a type of reaction between a (carboxylic) and an acid group. A catalyst such as sulfuric acid or phosphoric acid was used.
The following reaction occurs if an esterification occurs between salicylic acid and acetic acid:
o CO2H CO2H
CH3 C O C CH3 + 2 2 O + H2O
OH OCCH3
Acetic anhydride salicylic acid
Reaction of acetic acid with salicylic acid:
For the purpose of this experiment were acetic anhydride used. The advantage of using acetic anhydride is that half of the concentration of acetic anhydride is needed in comparison to the concentration of acetic acid.
Recrystalisation
In order to obtain purer aspirin and to have a homogenous size distribution the aspirin was recrystalisisted. Aspirin was recrystallized by the use of heated ethanol as a solvent for the impure solid. It is important for the process of recrystalisation to choose a solvent where the impure solution is fully dissolved when it is heated up. However, the product needs to be not soluble at low temperatures. After cooling the solution, the product is not soluble in the solvent at low temperatures and will crystallize. However, the impurities stay dissolved in the solvent.
The crystals can be extracted from the solution by using a vacuum filtration. The residue need to be rinsed with distilled water. The water needs to have a low temperature to avoid that the crystals dissolve again. Moreover, the rate of crystallization influenced the purity of the product and the concentration of the product obtained. Smaller and more crystals are obtained by a higher rate of crystallization. A higher purity can be obtained by a lower rate of crystallization.
Method
Hydrolyse of methyl salicylate
Products and instruments used
· Gloves and glasses
· Reflux apparatus
· 5M NaOH
· 7.5 g methylsalicylate (liquid)
· 3M H2SO4
· Boiling stones
· Round bottom flask
· Cork holder for round bottom flask
· Heating mantle
· Reflux condenser and tubing
· Glass beaker 125 mL or more
· pH-paper
· Ice
· Büchner funnel
· Water vacuum pump
· Filter paper
· Sample container
Safety considerations
- Sodium hydroxide: It may cause serious eye damage in case of eye contact (Socrates Comenius & Education and Culture, 2006). Therefore any contact with it needs consult of medical help. Solid NaOH or dissolved is very corrosive and any skin contact with it or swallowing should be prevented. Finally, one should be careful when sodium hydroxide dissolves in water it releases significant heat.
- Methyl salicylate: Ingestion of this substance is hazardous, and can lead to coma therefore medical aid is needed incase of intake (Sciencelab.com, 2005). In contact with skin or eye can methylsalicylate cause irritation therefore should this contact be prevented. Inhalation is dangerous in case of inhalation medical help is required urgently. Explosion of it can be provoked by mechanical impact on the product or static discharge.
Procedures
7.5g of methyl salicylate was added to a solution of 5 M NaOH contained in a round bottom flask. To create an agitation within the solution during heating, few boiling stones were added. To heat the solution, it is put in an heating mantel. The mantel’s shape fits completely to the shape of the flask in order to increase the surface contact with the heat. The flask is then connected to a condenser to avoid evaporation of the solution in the flask. After 20 min of heating, the flask was removed from the heat and added to a 125 ml beaker with 3 M H2SO4 until the pH reached 3. To neutralize the solution NaOH was used. To stop the reaction the solution was then put in a container filled with ice. When crystallization was over, the solution is filtered using a Büchner funnel. The residue in the filter is collected and put in the stove to dry completely for around two hours.
Esterification of salicylic acid
Products and instruments used
· Gloves and glasses
· Acetic Anhydride, about 15 mL
· Ethanol, keep away from flames
· Salicylic Acid, about 10 g and/or your own produced salicylic acid, do not inhale!
· A few drops (10) concentrated sulfuric or phosphoric acid
· Distilled water (flask)
· Sample container (red) for crystals
· 1 hotplate and 1 warming mantle
· 250 mL round glass flask + cork standard
· Büchner funnel with rubber stopper and filter paper
· Suction flask and Rubber hose to filter the crystal suspension
· Thermometer
· Ice
· Clamps and aluminum bars to build experimental set-up
· Glass test tubes to test aspirin purity
Safety considerations
- Acetic anhydride: This substance is very corrosive and may cause serious burns in case of contact with the skin of the eyes (Socrates Comenius & Education and Culture, 2005). In case of contact with the body, abundant rinsing is required as well as medical assistance in some cases. Also in case of inhalation or swallowing it is hazardous and corrosive so medical assistance is compulsory. Furthermore, when mixing this substance with water or alcohol, it can react violently so one should be careful using it.
- Ethanol: This molecule can also irritate the skin and cause serious irritation in case of contact (Socrates Comenius & Education and Culture, 2004). Ingestion of it, if large amount, can damage the liver and other organs. It is said that it increases the risk of cancer and can be fatal. The last but not the least, it is a very flammable substance therefore avoid closeness to a source of fire.
Procedure
Fig1: Production of aspirin from salicylic acid.
Around 7.1g of dried initially prepared salicylic acid is taken from the stove and added to a solution of 15ml acetic anhydride which shifts the equilibrium. This is done under the hood to avoid inhalation of the dangerous products. Then a few drops of H3PO4 are added to the solution for esterification. This oxidant is used instead of stronger one to produce aspirin of white colour. The solution is then heated in a water bath of 80-Celsius degree for 15 min until Salicylic acid is completely dissolved. It is then cooled while stirring and added cool water to stop the reaction. Water is added progressively to make the temperature decrease slowly and formation of crystallization proceeded in an optimal way. The solution is then filtered in Büchner funnel to separate the crystals from the solution. The precipitate is washed with distilled water, while filtering, a couple of times to remove acetic acid and phosphoric acids. A pinch of the solid is taken and tested with 1% FeCl3 for purity. If the test colours violet, it indicates presence of salicylic acid left in the precipitate, otherwise the test is colourless. Then the solid is checked under the microscope for crystal properties.
Afterwards, the recrystaization of the aspirin is performed; Ethanol is boiled in a closed glass flask to avoid evaporation. Small amount of boiled ethanol is added to the previous made precipitate to dissolve, and is recorded. Then, two times more water than ethanol( heated up to 70 degrees) is added to the solution. And immediately Ice blocks are added to stop the reaction while stirring, and precipitate is seen. The precipitate is then filtered with Büchner funnel. Again a pinch of the precipitate is tested 1% FeCl3 for purity. The aspirin is finally formed. It is put in stove to dry completely. After it is dried out, it is weighed.
Results
Purity
It was tested for the purity of the crystallized and filtered aspirin by using FeCl3. After adding some drops of FeCl3 the solution was colourless. This indicates that the amount of salicylic acid which was left among the aspirin crystals is very small. Moreover, large crystals could be depicted in the final aspirin obtained.
The mass of aspirin calculated by the mass of salicylic acid obtained
The mass of salicylic acid obtained was 7.1g. The molar mass of salicylic acid is 138.123g/mol. Therefore , 0.0514 moles of salicylic acid were synthesized. By the esterification of one mole of salicylic acid one mole of aspirin is theoretically produced. Therefore should theoretically 0.0514 moles of aspirin been produced. This equals to 0.0514*180.2g or 9.01g of aspirin. These results are impossible considering the amount of methyl salicylate we started with. Therefore, the mass of salicylic acid produced is too high. This might be explained by the fact that still some water or other products might have been present in the salicylic acid when it was weighted.
The theoretical mass of aspirin
Theoretically we should have obtained 8.8 g of aspirin. 7.5g of methyl salicylate were used in the beginning of the experiment. The molar mass of methyl salicylate is 152.1494 g/mol therefore 0.0493 moles of methyl salicylate were initially used. Consistently should the theoretical mass of aspirin obtained be 0.0493*180.2g or 8.88g.
Actual mass of aspirine we obtained
The mass of aspirin actually obtained was 1.72 g, which means that the yield of the reaction was 19% ((1.72/8.88)*100). As a conclusion one may say that the HO hypothesis ”the amount of salicylic acid initially used is not equal to the amount of aspirin synthesized” can not be rejected.
Discussion
The purity of the aspirin was satisfying. However, the actual amount of aspirin obtained was highly unsatisfying. The mistake in the experiment must have occurred in the second part of the experiment (the esterification process) since the amount of salicylic acid obtained was satisfying. Firstly, the mistake could have occurred during the recystalisation. Probably the solution with the heated ethanol was not colled down fast enough. Therefore, aspirin could have been lost due to the evaporation of the solution. Secondly, the amount of water when the crystals were washed could also have been too much. This could have caused the crystals to go through the filter.
References
Bayer HealthCare LLC. (2009). The History of Aspirin. Retrieved April 4, 2009, from http://www.bayeraspirin.com/pain/asp_history.htm
General Chemical. (2003). Material Safety Data Sheet Sulfuric Acid. Retrieved April 5, 2009, from http://www.genchemcorp.com/pdf/msds/Sulfuric%20Acid%20-%203-01.pdf
Sciencelab.com. (2005). Material Safety Data Sheet Methyl salicylate MSDS. Retrieved April 5, 2009, from http://www.sciencelab.com/xMSDSMethyl_salicylate-9927362
Socrates Comenius & Education and Culture. (2004). Chemical Safety Data: Ethyl alcohol. Retrieved April 6, 2009, from
Socrates Comenius & Education and Culture. (2005). Chemical Safety Data: Acetic Anhydryde. Retrieved April 6, 2009, from http://ptcl.chem.ox.ac.uk/~hmc/hsci/chemicals/acetic_anhydride.html
Socrates Comenius & Education and Culture. (2006). Sodium Hydroxyde. Retrieved April 5, 2009, from http://ptcl.chem.ox.ac.uk/~hmc/hsci/chemicals/sodium_hydroxide.html
Synthesis of Aspirin (acetylsalicylic acid) from Oil of Wintergreen (methyl
salicylate). (2006). Retrieved April 6, 2009, from http://aurora.wells.edu/~agodert/Classes/Chem214LabDocs/Lab3-Aspirin_Synthesis.pdf
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