Synthesis & purification of paracetamol.

Synthesis analysis and purification of paracetamol.


Table no. 1 Reagents list:
4-aminophenol (g)2.20
Acetic anhydride (ml)2.20
Propanone (acetone) (ml)20.00
Commercial paracetamol, 2 tablets (g)3.43
Ethyl acetate C4H8O210
Petroleum ether (ml)1


The aim of the experiment is to synthesize paracetamol in the control laboratory environment. Purification, Recrystallization, and comparison of synthesized sample to commercial brand paracetamol. Confirming of obtained substance by assessing melting point. Verification of purity based on Thin Layer Chromatography TLC. Reaffirmation that samples contain paracetamol will be conducted by Infra-Red spectroscopy IR. To validate results three different assay techniques were adopted. IR spectra. TLC paper chromatography. The range of melting point was observed. The purity of the product is confirmed by melting point and by comparison to industry literature.

The reaction of 4-aminophenol with acetyl anhydride is conducted the final product will include paracetamol and acetic acid. The reaction is divide into two main steps the first one is addition second elimination. The amide bond is formed in paracetamol and the by-product ethanoic acid.


The exact mass of 4-aminophenol used as reagent equal 2.20g

Mass of recrystallized purified paracetamol equal 0.82g


Graphic no. 1


4-Aminophenol acetic anhydride paracetamol acetic acid

Ratio 4-aminophenol to acetic anhydride is 1:1

Weight of 4-Aminophenol used to reaction equal 2,20g.

Molar mass of 4-Aminophenol equal 109.128 g/mol.

n(C6H7NO)= 0.0202 mol

Volume of acetic anhydride equal 2.2ml

Volume of acetic anhydride = 0,0022dm3

Density of acetic anhydride = 1,08g/ml

Molar mass of acetic anhydride equal 102.089 g/mol.


mass(C4H6O3)= 2.2ml *1,08g/ml

mass(C4H6O3)= 2,376g

n(C4H6O3)= 0.0233 mol

C6H7NO : C4H6O3

Ratio 1:1

0.0202mol : 0.0233mol

4-Aminophenol is a limiting reagent Thus, has lower moles compare to acetic anhydride.

Acetic anhydride is an excess reagent.

Theoretical and actual yield calculations evaluation is based on limiting reagent. In this case, the limiting reagent is 4-Aminophenol observing the reaction it is concluded that the ratio 4-Aminophenol to paracetamol is 1:1 Therefore, n(4-Aminophenol) =n(paracetamol).

Theoretical Yield for paracetamol

Acetaminophen molar mass = 151.165 g/mol

Theoretical Yield = moles of acetaminophen * molar mass of acetaminophen

                         = 0.0202mol x 151.165/mol

                         = 3,0535 g

Actual yield of paracetamol = 0,82g

Actual Yield obtained in experiment.

Actual Percent Yield =          Actual Yield        x 100%

                             Theoretical Yield

                     =            0,82 g      x 100 %


                     =  26,85 %

Atom economy (Atom utilization)

atom economy =     (Relative formula mass of paracetamol) * 100%

                             (Sum of relative formula masses of reactants)

atom economy =    (paracetamol) * 100%

                             Mr(4-Aminophenol)+ Mr(acetic anhydride)

atom economy =    151.165 * 100%

                             109.128 + 102.089

atom economy =    151.165 * 100%

  109.128 + 102.089

atom economy =    71,56 %

Melting point

Sample of synthesized paracetamol was observed through the melting process, first visible liquid drop starts at 170°C and finishes at 179°C. Commercial paracetamol start melts at 176°C and finalized at 179°C.

The matching range of substance melting points may be used as a purity indicator. Comparison melting points to scientific articles is a way to ensure the purity of the synthesized substances. Contaminations or impurities in the sample will lower the melting point. Impurities in the sample will lead to extending the range when solid will change the state of aggregation to liquid. Based on this indicator experiment reveal that synthesized paracetamol contains undesired contamination. However, Bashpa et al. (2014) pointed out that the pure paracetamol melting point is 169°C. Conducted examination of 11 brands of paracetamol tablets fit in and coincide with the experimentally obtained melting results.

(IR) Infra-Red Spectrograph

IR Spectogram of paracetamol.

Paracetamol’s bonds interfere with the infrared light spectrum. IR sensors detect the energies of compound bonds. Analysis of obtained data aid to determine the type of bonds in the molecule Therefore, functional groups are marked as present in the molecule. IR spectrogram no. 1 represent reference spectrogram for pure paracetamol. The second chart reveals spectra for commercial brand tablets. The third one shows sample obtain in the laboratory. Visual investigation of charts leads to the conclusion that all examined samples contain paracetamol. Furthermore, Table no. 3 provides pieces of evidence for characteristic peaks and stretches.

Table no. 3 IR Spectrogram
IR spectrum Wavenumbers(cm-1)Functional group deduced.
1504C-C (aromatic)
Bonding pairs paracetamol molecule.

The presence of all these peaks leads to the conclusion that the obtained product is paracetamol. In addition, excellent similarities are clearly notable.

TLC Chromatography

Data gathered from Chromatogram no. 1 was used to calculate the Rf value. Synthesized paracetamol and its commercial brand equivalent are equal and have Rf = 0,44. No additional spots on their bar chart indicate about potentially high purity of both substances. Interesting results three different spots were observed for acetic anhydride. However, those contaminations may be the result of hydrolysis of acetic anhydride. Although, recrystallization of paracetamol and the purification process was conducted appropriately for both paracetamol samples.

Type of substanceDistance traveled in cmDistance to solventfrontDistance to solvent front in cmRValue
4-aminophenol C6H7NO3,56,40,54
acetic anhydride2,4 / 3,5 / 5,66,40,37 / 0,54 / 0,87
synthesized paracetamol2,86,40,44
commercial brand paracetamol.2,86,40,44
Paracetamol chromatogram. 4-aminophenol chromatogram.


Hand draw no. 1 present reaction and explanation of processes of addition & elimination in the aqueous solution of acetic anhydride and 4-aminophenol. The explanation why reaction required heat to occurs. Srabovic et. al. (2017) pointed out about solubility of 4-aminophenol in cold water. To obtain high yield solution is heated to approximately 90 degrees of C. 4-aminophenol dissolve successfully in water. Skip the step of heating solution will decrease the yield of paracetamol. Potential reagents contaminations and impurities dissolved in water. In process of the cooling solution when paracetamol crystals start to form significant numbers of contaminations stay in liquid. Therefore, the crystal form of the final product is purified & highly desirable. After the heating solution was cooled. The suspension was filtered by vacuum. Finally, the residue was flushed by cold water and left until water vaporized. Mass of paracetamol crystals was noted. To eliminate all residue contaminations the process of recrystallization was adopted. According to Srabovic et. al. (2017), paracetamol is insoluble in cold water. The mixture was heated and paracetamol dissolve. The solution was cooled down until reach room temperature. Cold paracetamol starts to crystallize. Vacuum flow and paper filter aid help to finish the process. The mass of paracetamol was noticed.


Each experiment is prone to external environmental conditions. Moreover, those conditions may negatively impact experiment accuracy and to final results obtained. On the first plan, hygroscopic properties of acetic anhydride should be considered. According to Chromatogram no.1 is visible that there are three different spots marked. Water presented in air interreact with acetic anhydride and therefore acetic anhydride hydrolyze. (CH3CO)2O + H2O → 2 CH3CO2H Concentration of acetic anhydride may be a matter of discussion. Acetic anhydride dissolves in water to approximately 2.6% of the mass. Each operation with liquid is prone to misreading burette and for incorrect addition of volume. It must be noticed that process of vacuuming starts rapidly. Uncounted mass of substance was lost in a process. Manifold with digital pressure valve to control airflow should be beneficial and will avoid further disappointment. It is recommended to wet paper filters to get a better grip between vacuumed substance and patch potential air leaks around. In general filtration, suction, as well as lack of researcher experience are major causes of errors.

Recommendations and suggestions

-accuracy and precision with weighting measuring and moving product.

-the slower process of crystallization

-decrease the volume of solvent required to wash residue to a minimum

-decrease the suction in vacuum pump


To conclude all of the mentioned pieces of evidence lead to formulating a statement that the synthesized product is definitely paracetamol. Determined melting ranges were matched to literature. IR spectrogram’s and TLC chromatogram’s results confirmed that the gathered product is paracetamol. Relatively low yield gathered 26.85%. High purity was gained despite the potential contamination of excess reagent. Purity and structure of molecule proven by three assay techniques simultaneously. TLC chromatograph does not show impurities in samples. The melting point for both samples of paracetamol is comparable with professional chemistry literature. IR spectra for both samples of paracetamol matched perfectly according to the paramount pure paracetamol source chart model obtained from IR device. Comparison to literature Bashpa et al. (2014), 11 commercial brands of paracetamol obtained similar melting points. To consideration should be taken the relatively too fast process of paracetamol crystallization. Extend the period of crystallization may be beneficial for yield. The calculated atom economy of 71.56% for the reaction is satisfactory. The method of synthesis paracetamol pointed out in this report should be taken into consideration. To summarise, take into consideration all listed issues as well as adopting mentioned recommendations will significantly improve further yields.


Bashpa et al. (2014) ‘Polymorphism of paracetamol: A comparative study on commercial paracetamol samples.’, International Journal of Chemical Studies, 1 (No. 6), pp. [Online]. Available at: (Accessed: 27.05.2021).

Srabovic et al. (January 2017) ‘Design synthesis and crystallization of acetaminophen’, Journal of Chemical, Biological and Physical Sciences, 7(1), pp. 218-230 [Online]. Available at: (Accessed: 27.05.2021).

(N/A) Graphic no 1 , Available at: (Accessed: 28.05.2021).

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