Aspirin Synthesis

Practical 2 : Organic Synthesis – Aspirin

Aims

The purpose of this experiment is:

The purpose of this experiment is to synthesize the drug aspirin from salicylic acid and acetic anhydride mixture, to examine the purity of aspirin by carrying out chemical testing and also to determine the yield percentage of the Aspirin drug synthesized in the sample at the end of the experiment.  

Introduction

Salicylic acid and acetic anhydride together makes up a compound known as aspirin (acetylsalicylic acid). Aspirin is one of the most widely used drug in the world.  It acts as an antipyretic drug which is used to reduce fever and as an anti-inflammatory to react with inflammation related swellings. Aspirin is also used as an analgesic which is able to reduce the mild pain such as headache and toothaches.  In addition, Aspirin also plays an important role in the cardiovascular related diseases as it can prevent the primary and secondary heart attacks besides preventing the blood clotting in the arteries.

The active ingredient in the aspirin (acetylsalicylic acid) is known as salicylic acid. This acid is the main ingredient in aspirin which plays the role to cure and prevent disease in human being. Salicylic acid is found in nature in the form of organic compound. It is found in the leaves of the willow (Salix). It is also found in the European dropwart, Spiraea.

Although salicylic acid able to cure the diseases in human being, it also exhibits some side effects. For example, consumption of this acid can cause the inhibition of formation of the prostaglandins. It corrodes the protective barrier in the stomach produced by the prostaglandins which can cause internal bleeding or worse cause’s peptic ulcers. The carboxylic acid groups and phenol groups in salicylic acid is too harsh towards the lining of the mouth, esophagus and stomach which to some extend can cause hemorrhaging.

Any unreacted salicylic acid in the aspirin can be detected by carrying out chemical test using 1% iron (III) chloride solution. The presence of unreacted salicylic acid can be confirmed by the changes of colour from colourless to purple. The purple colour is exhibited by the presence of phenol in the salicylic acid. If there are no changes in colour when the sample is mixed with 1% iron (III) chloride, it shows that there is no presence of salicylic acid in the sample and the sample can be considered as pure aspirin.

[pic 1]The synthesis of aspirin is as shown in the equation below:  [pic 2]

Procedure

• Preparation of aspirin

1. A water bath was prepared using a 400 ml beaker which was half filled with water. It was heated until the water boiled.
2. 2.0005 grams of salicylic acid was weighed using a weighing boat and was transferred into a dry 125 ml Erlenmeyer flask.
3.  3ml of acetic anhydride was then added to the Erlenmeyer flask containing salicylic acid carefully. 5 drops of concentrated sulphuric acid was added drop by drop while the Erlenmeyer flask was swirled. This step was carried out in a fume cupboard as the acetic anhydride and the concentrated sulphuric acid are dangerous to the eyes and skin respectively.
4. The flask was then gently swirled to ensure the even mixture of the solutions. The Erlenmeyer flask was then placed in the water bath prepared for about 30 minutes. This step was carried out to ensure the salicylic acid solids were completely dissolved in the solutions. The solution was swirled occasionally.
5. The Erlenmeyer flask was then removed from the water bath after the solids was completely dissolved. It was then left to cool at the room temperature.
6. The solution was then transferred to a 150 ml beaker which contained 20 ml of ice water. This beaker was then placed in an ice bath.
7. The bottom part of the beaker was scratched along using a glass rod and as well as to mix the solution. This step was done to aid in the precipitation of aspirin from the solution.
8. Buchner funnel was used to collect the crystals via filtration under suction.
9. The crystals were than washed with two portions of 5ml cold water and one 10ml portion of cold ethyl acetate.
10. The suction was continued for about 5 minutes to ensure the crystals was completely dried. The rubber tubing was disconnected from the filter flask before the water aspirator was switched off.
11. A re-crystallization process was carried out to purify the product obtained from the filtration. The crystals were then transferred to a 250 ml beaker using a spatula. 10 ml of ethanol was added to the beaker containing the crystals. The beaker was warmed while the mixture was stirred for the crystals to dissolve.
12. 25 ml of warm water was then added to the alcohol solution after the crystals have completely dissolved. The beaker was covered and once the crystals started forming, the beaker was then transferred to an ice bath to complete the re-crystallisation process.
13. The filtration step using the Buchner funnel was repeated.
14. The crystals was removed and pressed under the filter paper to remove excess water.
15. A 50 ml beaker was recorded and the weight was recorded and the beaker was reweighed with the crystals in it. The new weight of the beaker was also recorded.
16. The weight of the purified aspirin was counted.
17. The sample aspirin was than confirmed by determining the melting point of 135ºC using the melting point apparatus.

• Analysis of aspirin

1. A drop of 1% iron (III) chloride solution was added into the two separate test tubes containing aspirin sample and commercial aspirin respectively.
2. The change in colour was observed and recorded.
3. The purity of the sample was determined by obtaining the melting point of the synthesized aspirin sample.
4. The synthesized aspirin was reduced into fine powders by using a mortar and pestle. The fine powder was then loaded into a capillary tube for about 1-2 cm depth. The temperature where the fine crystals started melting and the final temperature where the crystals were completely melted were recorded.

[pic 3]

Diagram 1: filter under suction using Buchner funnel.

Safety precautions

1. The whole experiment was carried under the supervision of lab assistant.
2. Lab coats, gloves and mask were worn during the entire experiment duration. The long hairs were tied up during the experiment to avoid any unwanted accidents. No experimental steps were carried out without wearing the lab coats, gloves and mask.
3. The chemicals such as acetic anhydride and sulphuric acid were handled in the fume cupboard as these are highly dangerous. This is because the acetic anhydride can cause irritation to the eyes and the sulphuric acid can cause burns to the skin if it came into contact with the skin.
4. Extra care was needed during the scratching step so that no harm was done to the apparatus used.
5. The hot apparatus was handled with care.
6. All the apparatus was handled with care and checked before conducting the experiment.
7.  All the waste was disposed into the particular waste bins and was not washed down into the sink.
8. The apparatus was washed and the table was cleaned at the end of the experiment.

Results and data

Table 1 shows the mass and volume of chemicals used in the experiment

Percentage yield of aspirin is calculated using the formula below:

 X 100 %[pic 4]

 Table 2 shows the molar mass and density of chemicals used in the experiment