Practical investigations
Read our general notes on Risk Assessment
Aspirin investigations (revised February 2007)
An investigation of aspirin might involve its laboratory preparation and a subsequent analysis, or possibly the analysis of commercial aspirin tablets, by a range of different techniques.
Investigations based on aspirin might involve its laboratory preparation and a subsequent analysis, or possibly the analysis of commercial aspirin tablets by a range of different techniques.
See also our sorted FAQs on aspirin investigations
1 PREPARATION OF ASPIRIN
Details of this are given in an excellent RSC publication available on the internet RSC Aspirin booklet pdf
Alternatively try
• I would like to know how to conduct an experiment for the synthesis of aspirin by the acylation of salicylic acid using ethanoic anhydride.
You will also find information here about the recrystallisation techniques necessary to purify your crude sample of aspirin.
Several relevant FAQs on React worth referring to are:
• I read a procedure regarding aspirin synthesis and noticed that they usually use phosphoric acid or sulphuric acid as catalyst. What will happen if hydrochloric acid is used? Will it have the same effect since HCl is also a strong acid?
• Is the reaction between ethanoic anhydride and a phenolic compound for the preparation of aspirin a nucleophilic substitution reaction? If so, which is the nucleophile?
• What is the purpose of refluxing during the production of aspirin?
• I would like to know why phosphoric acid was used in the synthesis of aspirin and how I would be able to obtain soluble aspirin.
• If 2.00 g salicylic acid reacts with an excess of acetic anhydride, calculate the theoretical yield of acetylsalicylic aid for this synthesis.
• I'm doing my Individual Investigation on Aspirin and I'm on stuck on the preparation of Aspirin because I don't know how to work out how many grams of 2-hydroxybenzoic acid to use. Please tell me how to work it out.
• I am currently doing my A2 coursework and am comparing the techniques used to assess the purity of aspirin, and I was wondering what the chemistry is behind the purification by recrystallisation of aspirin (as in what happens to the substance, as I am recrystallising it).
• I am going to do an investigation on preparation of aspirin. What method can I use to determine which synthesis is most efficient? Do I (also) have to include the method of recrystallization and thin layer chromatography?
One student has written in and asked about the conversion of aspirin to "soluble aspirin":
• What further reaction could you do to obtain “soluble” aspirin after recrystallizing the product, and why?
and another asked about the production of aspirin commercially:
• What is the industrial method of preparation for aspirin? What are the starting materials and what is the balanced equation? Thank you for your help.
2 ANALYSIS OF ASPIRIN
A range of techniques can be used, including the following:
a Melting-point determination
This is a useful technique to gain some idea as to the purity of your aspirin product. More details are available in the RSC publication mentioned above. RSC Aspirin booklet pdf.
Also refer to:
• What is the melting point of pure aspirin?
• I'm doing my practical investigation on the amount of aspirin in various brands of aspirin tablets and I was wondering if there is any point checking for the purity of the aspirin by checking the melting point. In order to do this, would I need to separate the aspirin in the tablet from the rest of the impurities? If so, how should I do that?
• May I know what are some of the impurities that may be found in preparing my aspirin when its melting point is a shocking 119.8 instead of 135?
• I am currently doing an investigation on the purity of aspirin. I have found that the melting point of aspirin is about 135 °C. However, when I crushed a SOLUBLE aspirin tablet to test the melting point the sample did not melt even at 200 °C. Can you tell me whether soluble aspirin has a different melting point and why it does not melt at 135 °C?
• What is the boiling point for aspirin?
b Thin-layer chromatography (TLC)
Once again, relevant details of how this can be carried out are given in the RSC publication already mentioned RSC Aspirin booklet pdf.
However, neither the melting point determination nor TLC will enable you to calculate quantitatively the purity of the aspirin sample. For this you need to use one of the techniques below.
c Direct titration
This involves the use of a standard solution of alkali. We have already given details of this in one of our FAQs:
• What type of titration could I use to analyse the concentration of aspirin in a sample? What chemicals would you need to carry out these titrations?
If this technique is used with laboratory-synthesised aspirin, it will need to be adapted, given that the main impurity is unreacted 2-hydroxybenzoic acid, and this too will obviously undergo neutralisation, as well as the aspirin. An idea worth pursuing is to carry out three titrations, the first with a fixed mass of pure 2-hydroxybenzoic acid, the second with the same mass of 2-ethanoyloxybenzoic acid (pure aspirin), and the third with the same mass of the prepared sample. The percentage composition of the mixture will be linked to the titration value for the sample as compared with that of the pure components.
Have a look at:
• I plan to calculate the percentage composition of lab-synthesised aspirin using interpolation (the suggested method on this site), and I have performed the required titrations (eg. for salicylic acid, ASA, and my sample). Can you suggest a step-by-step method to interpolation, or any relevant sites that describe this process? Thanks a lot, this site is very much appreciated by all of my fellow students on the Salters' course.
For aspirin tablets, in which the impurities are mainly insoluble inert binders, the acid content can be assumed to be almost entirely derived from the aspirin present.
d pH titration
This can be carried out using a pH probe possibly linked to a data logging device, and the data produced can be manipulated in a similar manner to those resulting from a direct titration using an indicator. If carefully carried out, the results from this type of procedure could perhaps yield more reliable information than that from a direct titration. Perhaps both techniques could be used and then compared.
e Back titration
This method involves destruction of the aspirin using a known excess of aqueous alkali, followed by a titration with a standard solution of an acid to determine the quantity of alkali remaining.
Once again there are several internal FAQ web references on this site which describe this technique.
• What would the ideal concentration of NaOH be if I were to hydrolyse aspirin before using back titration to find its purity?
• I have been reading the answers that are given which might help me with my investigation on the concentration of aspirin in various medical products. However, I am a little confused. What exactly does hydrolysis do to the aspirin? Do I have to hydrolyse the aspirin sample before "back-titration" ?
• I am currently writing up my A2 chemistry investigation (different methods of analysing aspirin), but am really stuck with the back titration calculations. Is there anywhere I can find similar calculations to follow?
• I'm doing a back titration for aspirin and have just completed it by hydrolysing the aspirin with excess sodium hydroxide and then titrating it with hydrochloric acid using phenolphthalein as the indicator. I am confused as to whether the aspirin reacts with 3 moles of sodium hydroxide or 2 moles and how to work out the mass of aspirin in the sample.
• I have done an experiment to analyse the aspirin content of aspirin tablets. I have used the method of hydrolysis with excess NaOH, and have then carried out a back titration with sulphuric acid. The equation for hydrolysis is:
CH3COOC6H4COOH + 2NaOH -> CH3COONa + HOC6H4COONa + H2O
I would like to know whether CH3COONa and HOC6H4COONa would act as buffers. If yes, would it affect the pH of the equivalence point during titration between sulphuric acid and sodium hydroxide in the latter part of the experiment? (as the sodium hydroxide is mixed with CH3COONa and HOC6H4COONa in the solution used for titration) What would the pH of the equivalence point of the above titration be?
• For my A2 individual investigation, I am investigating the techniques available for assessing the quantity of ASA in aspirin tablets. In one method, the back titration, I hydrolyse a sample of ASA-ethanol solution with NaOH by heating. I realise that the stoichiometry of this reaction is in fact 2:1 and not 3:1. However, in another method, the straightforward acid-alkali titration, I am titrating NaOH directly against a sample of ASA-ethanol solution. In this instance, the stoichiometry between NaOH and ASA appears to be 1:1. I wondered why the ratio should be different in this instance compared with the back titration. I suspect heating had something to do with the discrepancy. Please could you help me?
• I am currently working on my formal report on the quantitative determination of ASA in aspirin tablets using a back titration. Can you tell me what is the rationale behind the dilution and aliquoting of the aspirin sample? Also, what are the principles behind the use of back titration in the analysis of aspirin tablets? Lastly, why are we using a more dilute solution of NaOH for standardization?
• I am performing the back titration of aspirin with NaOH and HCl to test the quantity of aspirin in a tablet. After adding the NaOH to the aspirin, how long do you leave it before you quench the reaction with ice, before removing portions to titrate?
• I'm carrying out an experiment on aspirin using a back titration. I've hydrolysed the aspirin and when I add the indicator to the hydrolysed solution it turns pink which shows that NaOH is present in it. But when I start to add my sulphuric acid solution from the burette, it went colourless. I don't know why it is going in a reverse order. Can you help me? Or have I got nothing to worry about?
• I’ve done a back titration to find the aspirin content in two different manufacturers’ aspirin tablets. One of these tablets contains lactose, which has given a higher burette reading to the other tablet that just contains starch, why is this? The aspirin was hydrolysed using sodium hydroxide, and then back-titrated with sulphuric acid, using a phenyl red indicator. Please help!
• I am trying to test the purity of my aspirin but when I refluxed my aspirin sample with a known quantity of sodium hydroxide and then, after it had cooled down, I titrated a known amount of sulphuric acid but nothing happened. I don’t understand why the sulphuric acid didn’t react with the excess sodium hydroxide. I did add an indicator. Is it possible that the ethanoic acid interferes with the titration?
Perhaps it would be helpful to include some theory at this stage, since the chemistry underlying this particular back titration is rather complicated and difficult to find in text books.
The full alkaline hydrolysis involves a reaction between one mole of aspirin and three moles of sodium hydroxide. This can be divided into two steps, for the purposes of discussion:
1. Hydrolysis of the ester link:
CH3COO.C6H4.COOH + 2NaOH -> CH3COONa + HO.C6H4.COONa + H2O
2. Reaction of the phenolic -OH:
HO.C6H4.COONa + NaOH -> NaO.C6H4.COONa + H2O
When the back titration is carried out, using, for example, dilute hydrochloric acid, the excess alkali is destroyed (reaction 3), and the phenoxide ion gains a proton and changes into a phenol group (reaction 4):
3. NaOH + HCl -> NaCl + H2O
4. NaO.C6H4.COONa + HCl -> HO.C6H4.COONa + NaCl
To a phenolphthalein end-point this is as far as the neutralisation proceeds. However, with greater quantities of acid, and at lower pH levels, the two salts,HO.C6H4.COONa and CH3COONa would be converted into their parent acids, HO.C6H4.COOH and CH3COOH.
The convention is to use phenolphthalein as the indicator, to stop at the first stage of the process (reactions 3 & 4), and when this neutralisation point has been reached, two moles of sodium hydroxide are still “tied up” in the two salt products, HO.C6H4.COONa and CH3COONa.
So, the stages of the calculation are:
1 Use the titration reading to calculate the moles of HCl required to reach this stage of neutralisation. This value also represents the number of moles of NaOH used (reactions 3 & 4), above and beyond the conversion of aspirin to these two salts.
2 Calculate the number of moles of NaOH originally added to hydrolyse the aspirin, and, by subtraction of the amount of NaOH obtained above, deduce the net quantity used up in the hydrolysis step itself (reaction 1).
3 Given that in reaction 1 one mole of aspirin needs two moles of NaOH to form the two salts, deduce the original number of moles of pure aspirin used.
As with earlier techniques, this procedure is most simply used for aspirin tablets, but could theoretically be adapted as described earlier for laboratory samples of aspirin, in which the main impurity, 2-hydroxybenzoic acid, will obviously interfere with the procedure.
f Colorimetric method
We now have several FAQs about this technique. These can be found at:
• I am planning my A2 chemistry coursework, and I have decided to investigate the different methods used to determine the purity of aspirin. The sheet suggests the use of colorimetry and iron(III) chloride. I am familiar with colorimetry, but don't know why I need to use iron(III) chloride in colorimetry nor do I know its relation to aspirin. If you could tell me how I relate it to colorimetry and/or aspirin, it would be a great starting point for me.
• For my advanced higher chemistry investigation I am trying to determine how much aspirin is in aspirin tablets by two different methods. One is colorimetry. I am using a colorimeter that reads absorbance but I need to know how to change this into percentage transmission as my calibration graph is of percentage transmission against mass of aspirin rather than absorbance.
• Hi, I'm really stuck. I'm doing my individual investigation on methods for testing the purity of aspirin. I did colorimetry with copper(II) nitrate. I got the method from school. I have been trying to find out about the Cu-aspirin complex and how the method works, but I can only find information on colorimetry with iron(III) chloride. Is my method correct? And what does the Cu-aspirin complex look like?
• Hiya, I’m doing my Salters A2 chemistry investigation at the moment. I've been investigating aspirin. I'm doing fine with it but I’ve become a bit stuck when it comes to calculating the percentage error for the evaluation. It’s not a regular problem - I understand how to do it generally. I’m just not sure how to work it out for a colorimeter. I mean I assume there's quite a high intrinsic error but I can't find out what it is.
Also working out the other errors is a little odd as well because our colorimeters go from zero to two rather than zero to one hundred, but I think that's just the log of the percentage absorbance. Thanks in advance. Alison
• I am planning an investigation to determine the concentration of aspirin in urine. I need to create a calibration curve using iron(III) chloride and a colorimeter. The aspirin solution has been dyed yellow, but it is still not the same colour as the urine. How can I eliminate the factor of the colour of the urine from the experiment? Is it possible to place the urine sample in the colorimeter and subtract the percentage of light not transmitted from the reading obtained after the iron(III) chloride has been added? Also what is the equation for the reaction between aspirin and iron(III) chloride?
• I'm doing an experiment on how to identify a drug as aspirin, paracetamol or ibuprofen by reacting them with neutral iron (III) chloride, noting colours and then heating it and noting any other colour changes. Ibuprofen doesn't have an OH group in it, so it doesn't change colour. However, paracetamol does, and so does aspirin after heating.
I'm having trouble explaining how the Fe3+ ion reacts with the enol group - what exactly does it do to make it change colour? (I've read the chemguide tutorial and didn't understand a word of it ... ) Help much appreciated!
• I’m investigating the purity of aspirin using colorimetry. I know how to set up a calibration curve with iron(III) chloride. However once I have hydrolysed my aspirin do I have to add a certain amount of iron(III) chloride to this in order to compare it with my calibration curve?
A wide range of colorimeters is available in many schools and colleges, and excellent results can be achieved using very straightforward instruments. However, a careful choice of filters is recommended for best results. Achieving this is often a matter of trial and error.
We recommend the use of a web-based search program such as Google to research some or all of these methods in greater detail. You may well find information about other techniques too.
3 MISCELLANEOUS FAQs ON ASPIRIN
• Why is it that pure aspirin is not sold commercially?
• Hi. I have discovered that aspirin can undergo autocatalytic degradation to produce salicylic acid and ethanoic acid. Can you explain to me how this works as I do not completely understand this concept?
Rate this page or react
Share your views on this page, 360 ratings so far
3
, rated at 
Reactions
Heather
I would just like to thank everybody involved including students for making this site so helpful. Keep up the good work!
11 February 2008
Ad
Hey, i jst wanna say thanks, bcuz this site is actually amazing, its like EVERYTHING you need to know, in one place :)
05 February 2008
Sheraz
Hey guys, just wanted to let you know that the website is ACE! i was really worried about my fast-approaching coursework but now after just 1hour of browsing your website, i feel much more relaxed and ready to face the coursework ahead.Bring it on!
Thank you so much!
27 August 2007
emmanuel
I don't know how to thank the person who runs this site. It has helped me a lot with my individual investigation. Thank you very much.
18 February 2007
Chris
Thanks alot, this site is very much appreciated by all of my fellow students on the Salters' course.
06 February 2007
updated: 12 March 2008
