oxidation of alcohols

aspirin hydrolysis

2. COMPARISON OF ASPIRIN HYDROLYSIS
AT AMBIENT AND ELEVATED TEMPERATURE

2.1 Objective

Prepare a calibration curve and follow the hydrolysis of Aspirin® solution at ambient temperature and at elevated temperature. Compare and discuss the results.
 

2.2 Background

Aspirin® is the trademark for ester - acetylsalicylic acid - which is a prescription-free drug, used in therapy of painful, inflammatory and feverish states. The active ingredient in Aspirin also prevents infections and damage to blood vessels. The efficiency of any drug depends on its chemical stability. Hydrolysis of the drug can be a major reason for the instability of drug solutions. Thus, when Aspirin undergoes hydrolysis, the degradation products are salicylic acid and acetic acid.

Salicylic acid forms with Fe3+ ions violet-blue complexes. The intensity of the colour depends on the salicylic acid concentration in a sample.
 

2.3 Equipment and reagents

  • Aspirin® 100,
  • Salicylic acid (2-hydroxybenzoic acid),
  • Fe(NO3)3·10 H2O,
  • HNO3 conc.,
  • Ethanol (95%),
  • Beakers, plastic reagent bottles, 250, 100, 25 mL volumetric flasks, pipettes.
     

Hazards

Salicylic acid

Inhalation causes irritation of the mucous membrane and upper respiratory tract. Contact with skin causes irritation and possible burns, especially if the skin is wet or moist. If absorbed, may cause symptoms similar to those for ingestion. May cause skin rash and eruptions.

R 22-41, S 22-24-26-39
 

Iron(III) nitrate(V) (decahydrate)

Inhalation causes respiratory tract irritation. May cause methemoglobinemia, cyanosis, convulsions, tachycardia, dyspnoea, and death. May cause acute pulmonary edema, asphyxia, chemical pneumonitis, and upper airway obstruction caused by edema. Skin contact may cause severe irritation and possible burns.

R 8-36/38, S 26
 



Nitric(V) acid

Inhalation causes respiratory tract irritation, delayed effects, pulmonary function changes, chemical pneumonitis, pulmonary edema, and dyspnoea may occur. Contact with skin causes severe burns, ulceration, scarring, dermatitis, and yellow staining of the skin may be observed.

R 8-35, S 23.2-26-36-45
 

Ethanol

Inhalation may cause dizziness or suffocation. Contact with skin causes moderate skin irritation.

R 11, S 7-16


2.4 Procedure

Preparation of a calibration curve:

  1. In a 100 mL volumetric flask dissolve 0.100 g of salicylic acid in a mixture of 10 ml ethanol and 10 mL of deionised water. Add deionised water so that the final volume of the solution is 100 mL.
  2. Take 2.5 mL of the salicylic acid solution and dilute it to 25 mL with a mixture of ethanol/water 1:1 in a 25 mL volumetric flask This is solution A.
  3. Transfer solution A into a small plastic reagent bottle.
  4. In a 25 mL volumetric flask dissolve 1.00 g of Fe(NO3)3·10 H2O in 20 mL deionised water, add 1 mL of conc. HNO3 and deionised water to 25 mL. This is solution B.
  5. Transfer solution B into a small plastic reagent bottle.
  6. Prepare solutions on a blister as follows: 
     

    7. Holes on blister

    1.
    blank

    2.

    3.

    4.

    5.

    6.

    7.

    8.

    9.

    Solution A

    0S

    1S

    2S

    3S

    4S

    5S

    6S

    7S

    8S

    Solution B

    1S

    1S

    1S

    1S

    1S

    1S

    1S

    1S

    1S

    Deionised water

    8S

    7S

    6S

    5S

    4S

    3S

    2S

    1S

    0S

    T (%)

     

     

     

     

     

     

     

     

     

    A

     

     

     

     

     

     

     

     

     

    Concentration of salicylic acid (mg/L)

    -

    12.5

    25.0

    37.5

    50.0

    62.5

    75.0

    87.5

    100
  1. For measuring the transmittance use green LED.

? Write the measurements in the table above and calculate the absorbance.

? Prepare a calibration curve:

Calibration curve

Hydrolysis of Aspirin tablet

  1. Weigh 1 tablet of Aspirin 500 and dissolve it in 10 mL of mixture ethanol/water 1:1.
  2. Filter the solution into a 250 mL volumetric flask, rinse the filter paper with 10 mL solution ethanol/water 1:1 and dilute the solution to 250 mL with deionised water. Transfer this solution into a small plastic reagent bottle.
  3. Prepare a blank (1S of solution B and 8S of deionised water) and set the transmittance at the green LED to 100%.
  4. Put into the next hole of the blister 8S droplets of Aspirin solution and add 1S droplet of solution B.
  5. Record the transmittance of the Aspirin sample. This is the transmittance of Aspirin solution obtained immediately after the solution preparation.
  6. Repeat the measurement of the transmittance of Aspirin solution, e.g. after 3 hours, 24 hours and 48 hours. Before the measurement, set the transmittance to 100 % using the blank as described in item 3.

? Calculate the absorbance from the transmittance and write the results in the table below.

Sample of aspirin solution

Transmittance
(%)

Absorbance

Taken immediately after the preparation

98.8

0.005

Taken after 3 hours

98.0

0.009

Taken after 24 hours

94.0

0.025

  1. Using the calibration curve, discuss, what is the reason for the increase in absorbance.
  2. Repeat the experiment of Aspirin hydrolysis, but this time keep the small reagent bottle with the Aspirin solution in the water bath at elevated temperature (e.g. 70 °C) and record the temperature of the water bath and the time.
  3. Compare the results obtained at ambient temperature and at elevated temperature, and discuss the differences.

Worked example

Ambient temperature

Absorbances of the Aspirin solution at ambient temperature were: 0.005 after dissolving, 0.009 after 3 hours, and 0.025 after 24 h. These results show that at ambient temperature acetylsalicylic acid, the active ingredient of Aspirin, undergoes hydrolysis, very slowly, and the concentration of salicylic acid, which forms the coloured complex with the reagent is increasing with time.

Elevated temperature

Absorbance after heating the Aspirin sample solution for 15 minutes in a water bath at 70 °C was: 0.016, after heating for 30 minutes it was 0.032, after 45 minutes 0.071, and after 60 minutes 0.090. These results show that the rate of hydrolysis is temperature dependant; at elevated temperature the hydrolysis of acetylsalicylic acid is much quicker than at ambient temperature.


Developed and prepared by: Margareta Vrtačnik*, Vida Mesec* and Nataša Gros**
*University of Ljubljana, Faculty of Natural Sciences and Engineering
**University of Ljubljana, Faculty of Chemistry and Chemical Technology