F336- aspirin individual Investigation

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Does Temperature Affect The Yield And Purity Of Aspirin?

        

Contents

        

Objectives

  1. Research using various sources on aspirin with reference to; history ,use in medicine and methods of synthesis
  2.  produce a sample of aspirin using a method found during research  
  3. Verify the presence of aspirin and use various method to measure the purity of the manufactured aspirin
  4. Carry out investigation to see if temperature effects  the yield and purity of aspirin

        

Research

History of aspirin

400 BC, Greece - Hippocrates recommended a brew made from willow leaves to ease the pain of child birth.

1763, England - A reverend called Edward Stone was walking through a meadow in Oxfordshire while suffering from an acute fever. Stone removed a small piece of bark from a  tree and nibbled on it. He was struck by its extremely bitter taste, as an educated man he knew that he bark from Peruvian  tree (which has a similar taste) is used in the treatment of malarial fevers. He surmised that the  might also have therapeutic properties. He gathered and dried a pound of  bark and created a powder which he gave to about fifty people. It was consistently found to be a “powerful astringent and very efficacious in curing agues and intermitting disorders”. He had discovered , the active ingredient in .

 1828, Germany- Johann Büchner isolates pure salicin from willow bark. Salicin is the compound in willow bark that relieves pain. The name salicin was derived from salix, which is the Latin word for willow tree.

 1853, France- Charles Frederic Gerhardt first   (ASA), but he fails to understand its  and its potential importance to humanity. His  is not pure and therefore of limited use.

1874 Dresden, Germany - Salicylic acid is first made industrially using Kolbe's method in Dresden, Germany. It is sold as a painkiller but, it also caused digestive problems such as  irritation, bleeding, , and even death when consumed in high doses.

1897, Germany,  - Felix Hoffmann, at Bayer pharmaceuticals, chemically synthesizes a stable form of ASA powder that relieves his father's rheumatism. The compound later becomes the active ingredient in aspirin named - "a" from acetyl, "spir" from the spirea plant (which yields salicin) and "in," a common suffix for medications. So from that day forth  became known as aspirin which did not have the unpleasant side effects that  caused. 

1899 - Bayer distributes aspirin powder to physicians to give to their patients. Aspirin is soon the number one drug worldwide

1915-Aspirin becomes available without a prescription. Manufactured in tablet form and used to treat symptoms of pain related to rheumatism, lumbago & neuralgia.

1930 - Bayer’s patent on aspirin runs out.

1948 - Dr. Lawrence Craven discovers that men to whom he prescribed aspirin suffered no heart attacks. He recommends "an aspirin a day" to both patients and colleagues alike to decrease risk of heart attack.

1985 - FDA approves aspirin to prevent heart attack in patients with previous attacks or unstable angina pectoris.  

Structure of aspirin:

                               

Many medicines are derived directly from plants.  The plants are studied, experimented on. Powders or resins are formed from them, which are then purified and go through rigorous testing process (animal and then human trials) if the compound is successful then it is approved as a medicine and manufactured for use. However there are problems with obtaining medicine from plants which include:

  • Difficulty of obtaining the plant due to location
  • Supply may be seasonal
  • Not enough can be grown to meet demand

So for these reasons chemist try and find ways to make medicine artificially. Chemist then began work on making Salicylic acid or 2-hydroxybenzoic acid artificially.                                            The first thing chemist do is to find a well known, abundant molecule that has a similar structure to Salicylic acid that can be modified. The answer... Phenol.  

 A German chemist Hermann Kolbe heated sodium phenoxide under pressure with CO2 and the reaction mixture was then acidified to yield salicylic acid. This is known as Kolbe synthesis

 

So now chemist could make aspirin without the need of the willow tree and make it in much larger quantities.  

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Possible impurities

If the reaction is incomplete or if you mix the reagents in the wrong proportion, your aspirin will be contaminated with unreacted salicylic acid. It might also contain ethanoic acid or the acid catalyst. Washing the solid product well and recrystallising it may reduce the degree of contamination but it might even have the reverse effect. This is because if you start off with aspirin tablets, they may be hydrolysed in humid conditions, producing salicylic acid and ethanoic acid again:

 Thin-layerchromatography                                                                                                                                                                             A fairly simple way of detecting salicylic acid and aspirin in a mixture is to use the technique of thin-layer chromatography. Dissolve the samples in ethanol and use pentan-1-ol as the moving solvent. After you have run the chromatogram, you can detect the positions of the spots by putting the plate under a ultraviolet light. Thin-layer chromatography is a qualitative procedure. If the level of impurity in your sample is low, you may not be able to detect it.

A back titration

There is also a different acid-base titration you can do to find out about the purity of your aspirin. It is an example of what chemists call a 'back titration'. In this technique you should heat about 1.5 grams of your sample with about 50 cm3 of .5 mol dm-3 sodium hydroxide solution for 10 minutes. Under these conditions the aspirin hydrolyses and the acids ionise:

                                                                                                            By titrating this solution with 0.5 mol dm-3 hydrochloric acid you can find out how much sodium hydroxide is left. Remember that each mole of aspirin reacts with two moles of the base while any salicylic acid in the sample will react with only one mole. So you can find out the composition of the original sample

A colorimetric technique

Colorimetric technique helps find out about the purity of your aspirin. The method depends upon the key observation that salicylic acid forms an intense purple coloured complex with Fe (III) ions as a consequence of the phenol group in its structure but pure aspirin gives no colour because the phenol group has been converted into an ester. One approach is to dissolve about 0.2 grams of sample in a 50/50 water/ethanol mixture in a volumetric flask, adding 1 cm3 of a 5% aqueous iron (III) ammonium sulphate solution before adjusting the volume to 100 cm3. The light absorption is best measured around 530 nm with the whole process repeated using different amounts of salicylic acid to construct a calibration curve.

Methods for making aspirin

Method 1:

This method involves using salicylic acid, pyridine, acetic anhydride, boron trifluoroetherate

What we do is place 1 g of salicylic acid into 4 test tubes and then to each test tube I add 2 ml of acetic anhydride. To the first test tube I add 0.2 g of anhydrous sodium acetate; in the second test tube I add 5 drops of pyridine. In the third and fourth tubes I add 5 drops of boron trifluoroetherate and 5 drops of conc. Sulphuric acid

I then place all the test tube in a hot water bath for 5 minutes to dissolve all the solid material. After I pour the content to all the test tubes into a 100ml conical flask and add 50 ml of water and swirl the mixture. Then I place the conical flask in cold ice for the solution to cool and crystallise. After 5 minutes I filter and collect the crystalline solid

Method 2:

This method involves using salicylic acid and ethanoic anhydride with sulphuric acid as a catalyst and glacial ethanoic acid

First I add together 2g of salicylic acid and 4ml of ethanoic anhydride in a 100ml conical flask. I then stir the mixture well and then add 5 drops of sulphuric acid. Then add 4 ml of ice cold glacial ethanoic acid and swirl the flask gently for 10 minutes. After that I pour the mixture into a Buchner funnel (vacuum filtrate) and extract the crystalline solid.

Decision

I have chosen to synthesise aspirin using method 2. I have chosen this method because:

  1. It is less complicated that method 1 and involves measuring out less chemical so the chance of error (human and /or equipment) is less.
  2. There are fewer chemicals involved so the aspirin I make using method 2 will be purer than the aspirin I make in method 1
  3. boron trifluoroetherate is highly corrosive and not practical to use in a school laboratory  
  4. I will scale up the quantities shown in method 1  as I will need a sufficient amount to perform repeats which I am analysing the purity of aspirin.
  5. I will need to increase the amounts stated within method two if I am to obtain a reasonable yield for my analytical methods.

 

 

Analytical methods

Thin layer chromatography (TLC)

Chromatographic techniques are used extensively in the chemistry organic laboratory for routine analysis. Thin layer chromatography (TLC) can be used to determine the purity of a compound, to analyze the composition of a mixture or to follow the progress of a reaction. The components of a mixture are differentiated by exposing to two competing phases, the stationary and the mobile phases. In TLC, the stationary phase is a polar adsorbent such as silica gel or alumina, which has been coated on a plastic plate. The mobile phase is an organic solvent. The solvent moves up the plate by capillary action.

A coated and dried glass or plastic plate is called a thin-layer plate. The mixture to be analyzed is dissolved in the solvent and applied as spots near the base of the plate. This is known as spotting. Spotting is achieved by repeated applications of the mixture from a capillary pipette (figure 1). When the filled pipette touches the plate, the liquid is delivered on to the plate by capillary action. The plate is immersed in a development chamber that contains a solvent or a mixture of solvents. As the solvent rises up the plate, it carries the mixture with it. The components of the mixture are separated on the stationary phase depending on their polarity. This process is known as developing or running the TLC plate. Polar compounds are attracted to the silica gel and are held more tightly compared to nonpolar compounds. A separation results due to the difference in rates at which individual components move on the plate. In general, nonpolar compounds move faster than polar compounds on a TLC plate coated with silica gel.

When the plate has been developed, it is removed and allowed to dry. There will a series of vertical spots on the plate (figure 2).  Each spot corresponds to a separate component of the original

mixture. If the components are colourless, the spots are invisible. To see the spots, a visualization method is used. Ultraviolet lamp is a common visualization method.

                                                                                                                                Figure 1                  figure 2

So relating this back to aspirin.

I can dissolve a small amount of our manufactures aspirin in a minimum amount of ethanol and do the same for salicylic acid and pure aspirin than I can apply these solution on the base line of our chromatography plate and place the plate into the mobile solvent which will be a mixture of solvent cyclohexane, ethyl Ethanoate, ethanoic acid   (200:100:1).

Wait 15-20 minutes and locate the spots using a UV light

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Colourimetry

So in the case of finding out the purity of the aspirin I have produced I must look at the chemistry involved.

Salicylic acid is a phenol and all phenols react with a neutral iron III chloride and produce a purple colour

So relating this back to purity, the solid aspirin  is made into a solution using a 50:50 ratio of water and ethanol, then neutral iron III chloride is added the concentration of the colour indicate the amount of  unreacted   salicylic acid present within the sample, therefore ...

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