dependence of the rate of hydrolysis of acetylsalicylic acid (ASA) Hydrolysis of the drug entity can be a major factor in the instability of solutions.
Aspirin (acetylsalicylic acid) for example, undergoes hydrolysis with the resultant degradation products being salicylic acid and acetic acid.
COOH
O C CH3
O COOH
OH + CH3COOH
Aspirin - acetylsalicylic acid salicylic acid acetic acid
The rate of this reaction is said to be second order, since it is dependent not only upon the aspirin concentration, but upon the hydronium ion concentration in solutions with pH values less than approximately 2.5, or upon the hydroxyl ion concentration in solution with pH values greater than approximately 7.0. If the solution is buffered so that the hydroxyl ion concentration remains essentially constant, the rate of hydrolysis follows first order kinetics.
1. Investigation of temperature-dependence of rate of hydrolysis
Accurately weighed 120 mg of acetylsalicylic acid is dissolved in distilled water in a 100 cm3 volumetric flask. About a 25 cm3 aliquot of the solution - in a dark, closed bottle - are kept in a water bath thermostatically controlled at a temperature of 60 ±1 °C, for 60 minutes. A similar experiment is performed in a water bath controlled at a temperature of 80 ±1 °C.
During incubation 5.00 cm3 samples are taken at the 20, 40 and 60 minute time points and the samples are immediately diluted with 5.00 cm3 of distilled water. To 1.00 cm3 of the diluted solution 4.00 cm3 of 1% iron(III) chloride solution is added, and the sample is kept in the dark for 15 minutes. Then, the absorbance of the solution is measured at 530 nm using a spectrophotometer against the mixture of 1.00 cm3 water and 4.00 cm3 of iron(III) solution (blank).
Identification number:
TÁMOP-4.1.2.A/1-11/1-2011-0016 97
2. Investigation of pH- dependence of rate of hydrolysis
Accurately weighed 120 mg of acetylsalicylic acid is dissolved in sodium carbonate (Na2CO3) solution of known concentration in a 100 cm3 volumetric flask. The concentration of the sodium carbonate solutions are
I. 0.00625 M Na2CO3
II. 0.0125 M Na2CO3
III.0.025 M Na2CO3
After dissolution, the pH of the acetylsalicylic acid solutions is determined by potentiometric measurements.
About a 25 cm3 aliquot of each solution - in a dark, closed bottle - is kept in a water bath thermostatically controlled at a temperature of 60 ±1 °C, for 60 minutes.
At the end of incubation 5.00 cm3 sample is taken and immediately diluted with 5.00 cm3 of distilled water. To 1.00 cm3 of the diluted solution 4.00 cm3 of 1% iron(III) chloride solution is added and the sample is kept in the dark for 15 minutes. Then, the absorbance of the solution is measured at 530 nm using a spectrophotometer against the mixture of 1.00 cm3 water and 4.00 cm3 of iron(III) solution (blank).
Salicylic acid concentration of the measured solution can be calculated by means of the calibration graph provided by the practice leader.
Based on the results of the first set of experiments, calculate the pseudo first order rate constant (k’) for both temperatures, the value of the activation energy, as well as the rate constant and the half-life of the reaction at room temperature (20 °C).
Based on the results of the second set of experiments calculate the pseudo first order rate constants of the hydrolysis occurring in the solutions of different pH.
(MW(acetylsalicylic acid) = 180, MW(salicylic acid) = 138.12) VI.3 Calculations
Decomposition of N2O5 occurs according to the following rate equation:
1.
[
2 5]
= ⋅[
2 5]
=3⋅10−2 min−1− k N O
dt O N d
What is the half-life of the reaction?
According to the integrated rate equation of the first order reactions:
t 0.693k
12 =
minutes 1
. 10 23
00 . 3
693 . 0
2 2
1 =
= ⋅ −
t
Thus, the half-life of the reaction is 23.1 minutes.
98 The project is supported by the European Union and co-financed by the European Social Fund Ethyl acetate undergoes base-catalysed hydrolysis according to the following 2.
stoichiometry:
CH3COOC2H5 + OH- = CH3COO- + C2H5OH
The second order rate constant of the reaction is 5.45 dm3mol-1min-1 at 20 oC.
Calculate the concentration of ethyl acetate at the 20 minute reaction time if 1 dm3 of 0.0400 M ethyl acetate solution was mixed with 1 dm3 of 0.0400 M potassium hydroxide solution. Temperature of both solutions was 20 oC.
On mixing concentration of both reactants is halved. Thus, [CH3COOC2H5]0 = 0.020 M
[KOH]0 = 0.020 M
The ethyl acetate concentration at the 20 minute reaction time:
[
EtOAc]
20 =[EtOAc]0 + k⋅t1 1
[
1]
20 0.0201 5.45 20⋅ + EtOAc =
[
1]
20 50 109 159= + EtOAc =
[EtOAc]20 = 6.29 ∙ 10-3 M
Thus, the concentration of ethyl acetate at the 20. minute time point is 6.3 ∙ 10-3 M.
A 0.150 M ammonium cyanate undergoes isomerization into urea:
3.
NH4OCN = NH2(CO)NH2
The reaction follows second order kinetics. The first half-life of the reaction is 9 hours and 27 minutes. What a mass of urea is formed in 1 dm3 reaction mixture at the 10 hours’ time point? M(NH2(CO)NH2) = 60.06 g/mole
For second ordered reactions:
[ ]
0 121 A t k
= ⋅
9 hours and 27 minutes = 567 minutes
150 . 0 567 1
= ⋅ k
150 . 0 567
1
= ⋅ k
Identification number:
10 hours= 600 minutes Based on solution of the previous calculation problem:
[ ]
0.150 0.012 600Thus, the amount of isomerized ammonium cyanate (equal to the amount of urea) in the 1 dm3 of reaction mixture is:
0.150 – 0.072 = 0.078 mol.
1 mol urea 60.06 g
0.078 mol urea x g x = 0.078 ∙ 60.06 = 4.7 g
Thus, it is 4.7 g urea formed in the reaction mixture over the 10 hours reaction time.
The counts of a sample from Sneferu pharaoh’s tomb containing 1.0 g amount of 4.
carbon is 8.1 per minute. Calculate the age of the sample if the count of a living organism containing 1.0 g amount of carbon is 15.3 per minute. (t1/2 (14C) = 5760 years).
For a given element, the decay or disintegration rate is proportional to the number of atoms and the activity (counts) measured in terms of atoms per unit time. The counts (A) measured in the 1.0 g amount of organic (14C-containg) sample is directly proportional to the number of the 14C isotopes (N): A = k ∙ N.
Since the decay rate is dependent upon the number of radioactive atoms, in terms of chemical kinetics, one can say that radioactive decay is a first order reaction process.
The decay can be characterized by half-life of the process. Half-life is the time period that is characterized by the time it takes for half of the substance to decay:
k t lnk2 0.693
12 = =
where
k = decay constant
100 The project is supported by the European Union and co-financed by the European Social Fund
1
According to the relationship describing first order kinetics:
[A]t = [A]0 - k ∙ t
Radioactivity of a substance is reduced to ¼ of its initial activity in 25.0 s. What is 5.
the first order reaction rate constant of the radioactive decay?
For first order reactions:
[ ] [ ]
AtIdentification number:
TÁMOP-4.1.2.A/1-11/1-2011-0016 101