Synthesis of Aspirin

• 2g of salicylic acid was weighted and put into a boiling tube with a thermometer
• 4cm3 of ethanoic anhydride (acetic anhydride) was added to the boiling tube carefully. This procedure was performed in a fume cupboard. The mixture was stirred by thermometer gently and observation of the mixture and the read of the thermometer were recorded over the next 5 minutes.
• After 5 minutes, 5 drops of concentrated sulphuric acid was added to the mixture carefully by a glass pipette. This procedure was performed in the fume cupboard as well. The mixture was stirred by thermometer gently and observation of the mixture and the temperature were recorded over next 5 minutes.
• After 5 minutes, a test-tube holder needed to grip the boiling tube and placed into a steam bath for another 5 minutes.
• When the time is up, the boiling tube was removed from the steam bath and the mixture was poured into a 100cm3-conical flask.
• 2 cm3 of distilled water was added into the conical flask carefully. This procedure was performed in the fume cupboard as well. There may be a fairly vigorous reaction occurred but it didn’t have any in this experiment.
• 40 cm3 of water was used to rinse out the boiling tube.
• The flask was put into a container of ice in order to speed the cooling process.
• After few minutes, the flask appeared some crystals of the product. May used glass rod to stir the mixture to induce crystallization.
• After few moments, the crystals were filtered off by Vacuum filtration apparatus. The mixture was poured into a Buchner funnel with a filter paper first and sucked.
• 10cm3 of distilled water was used to wash the sucked production and dried in a filter funnel.
• The dried product was scraped from the filter paper in to a weighing dish. The product was weighted and the mass was recorded.

2nd part of the lab: Thin Layer Chromatography Experiment to test for Aspirin:

1. preparing of the TLC plate and container

• The TLC plate was provided. A fine pencil was used to draw a straight line across the plate from the short ends on the white side. About 5mm from the bottom and another line from about 10mm next to the 5mm line were drawn.
• 3 other parallel lines were drawn, about 5mm after each other.
• Marks “A” (aspirin), “S” (salicylic acid) and “P” (the product from 1st part of the lab) were written on the TLC plate above the bottom but below the first 5mm line.

2. Preparation of the “spotting” solution:

• Substance A was taken by a small spatula into a small, thin, screw topped sample bottle and a minimum amount of ethanol was added in to make a solution A. The small bottle shaken and waited for few minutes.

• Substances S and P were separately performed the same procedure as substance A.
• 3 bottles were marked correspondingly.

 2.3. Spot of the solutions on the TLC plate

• A clean extremely fine disposable pipette was used to spot the solution A onto the corresponding mark on the TCL plate, which only touched the plate twice.
• The spot was less 2mm in diameter and after spotting.
• Solutions S and P were separately performed the same procedure as the solution A by using other clean pipettes.

2.4. Performing the Thin Layer Chromatography:

• Sufficient eluent was added into a developing jar.
• The plate was place into the jar with a lid on.
• Waited about 3-4 minutes and taken out, which till the solvent front is approximately 5mm from the top of the plate.
• A line was drawn to indicate the final position of the eluent front.

2.5. Assessment of the chromatogram

• The plate was placed under a ultra-violet light.
• The positions of the compounds were marked by pencil.
• The distances from the bottom line to the marked point were recorded

2.6. at the end of the lab

• Used glasses dropping pipettes were washed and placed into the broken glass container.
• Product from the 1st part of the lab was put into a bag with the name on and so as the TLC chromatogram.
• Solutions A, S and P were disposed of in the organic solvents waste bottle
• Sample tubes and the lids were rinsed and placed into the tray provided.

Results

Chemical equation

In this experiment the chemical equation for the preparation of aspirin was:

(CH3CO)2O (l) + C6H4(OH)COOH (l)  H+  CH3COOH (l) + C6H4(OCOCH3)COOH (l) [ii]

     (1)            (2)                acetic acid             (3)

in which the structural formulae of the reaction was:

                     H+

[iii]

Observations

The temperature records and observations in the 1st part of the lab were following:

First 5 minutes (when 4cm3 of ethanoic anhydride was added in):

Second 5 minutes (when 5 drops of concentrated sulphuric acid was added in):

The temperature of the substance after took out from the steam bath was 95 ℃ and it was transparent fluid.

When further 40 cm3 of distilled water was added to the 100cm3-conical flask, there was some white precipitation appeared.

Calculations:

Mass

• The total mass of the final aspirin product was 0.1271g.

The molecular formula of aspirin was C6H4(OCOCH3)COOH

According to the molar formula  [iv]

Number of moles of aspirin

=

=

=0.71x10-3 mol (2 d.p.)

• According to the chemical reaction:

(CH3CO)2O (l) + C6H4(OH)COOH (l)  H+  CH3COOH (l) + C6H4(OCOCH3)COOH (l)

1mol of aspirin needed 1mol of salicylic acid

0.71x10-3 mol of aspirin needed 0.71x10-3 mol of salicylic acid.

In this experiment, used 2g of salicylic acid, so the number of moles of 2g salicylic acid= =0.0145mol

Hence, the percentage of the maximum quantity that the initial quantity of salicylic acid (yield percentage) = x 100 = 4.90% (2 d.p.)

• Excess quantity of ethanoic anhydride

There were 4cm3 of ethanoic anhydride used in the experiment

Density of ethanoic anhydride=1.08g/cm3

According to formula:   [iv]

Mass of total ethanoic anhydride used

=

=0.27g

According to formula   [iv]

Number of mole of ethanoic anhydride in chemical reaction

=

=

=2.65 x 10-3mol ( 2 d.p.)

0.71x10-3 mol of aspirin needed 0.71x10-3 mol of ethanoic anhydride

The excess quantity of ethanoic anhydride = 2.65 x 10-3mol - 0.71x10-3 mol

                                      = 1.94x10-3 mol

The reason for using more than the exact quantity required by the balanced chemical equation was to make sure there was sufficient ethanoic anhydride react salicylic acid completely.

The chromatogram

Final position of the

solvent front

                     

 Point of        Point of P solution

A solution

        Point of S solution

                                            

        About 5mm above the bottom

        

The above picture was the TLC plate from the experiment

The following were symbols for the corresponding substances and distances:

   --about 5mm interval

 A- Pure aspirin

 S- Salicylic acid

 P- Product synthesized from the 1st pat of the lab

-- Distance traveled by the compound

The retention factor ( Rf value) of a compound is

  [v]

and from the measurement of the experiment:

the distance traveled by compound A ( RA, pure aspirin) = 2.9 cm

the distance traveled by compound S (RS, salicylic acid) = 2.0 cm

the distance traveled by compound P (RP, crude product) = 2.6 cm

the distance traveled by the solvent = 4.5 cm

0.64 (2 d.p.)

0.44 (2 d.p.)

0.58 (2 d.p.)

Comparison

The value of the impure aspirin RfP compared with pure aspirin RfA, the difference between these two substances was only 0.64 – 0.58 =0.06, which was less than 0.01. Because the Rf value of a compound was constant on the same plate in condition of the temperature and solvent were kept the same and the closer the value of RfP and RfA the possible these two substances were the same. [v] So the crude product had a very high purity, which was very close to the pure aspirin.

Discussion

The sample was sent to John Innes Center to analyze the purity the week after. The John Innes Center used the ion trap mass spec to operate with a liquid chromatography system.

In order to analyze the sample, it was dissolved firstly and put into a tube in order to pump into the mass spec and because the aspirin was a single chemical the solution only needed to be trickled into it. Secondly, the solvent was dried directly due to the ions were already presented in an aqueous solution. After that, the ions were drawn into the mass spec by the electric field. The next step was to separate the ions by mass, this was where the ion trap occurred. [vi]

The graph of the mass spectrum of aspirin was attached in Appendix A. The big peak in the spectrum in the Appendix A was a fragment. The lower peak was expected 180 due to the molecular mass of pure aspirin was 180g/mol but it appeared 178.9, which was a negative ion chromatography. So there had a loss of H+.

In this experiment the purity of the product may due to some errors, such as product was not transferred completely from the boiling tube to the conical flask when salicylic acid reacted with ethanoic anhydride.

Reference

[i]  (Feb.2008)

[ii] Synthesis of Aspirin handout from Michele Raychaudhuri. (Feb.2008)

[iii] .  (Feb.2008)

[iv]Hand out of Lesson3-Atoms, Molecules and Stoichiometry from Michele Raychaudhuri

[v] Rob Lewis and Wynne Evans. Chemistry. Page 362. 3rd edition. 2006

[vi]  (Feb.2008)