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530-4-ASA hydrolysis

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```									                           KINETICS OF ASPIRIN DEGRADATION
Introduction

Aspirin (acetylsalicylic acid, ASA) is a drug that hydrolyzes according to the
chemical equation:
COOH                       COOH
O C CH3                    OH           O
O                                  HO C CH3
                     +
aspirin                   salicylic acid       acetic acid
(mw = 180)                   (mw = 138)          (mw = 60)

This hydrolysis is evident by the smell of acetic acid detected when a bottle of
aspirin is opened. The rate of hydrolysis is dependent on the temperature, pH and
amount of moisture present. In this experiment you will measure the rate of aspirin
hydrolysis in aqueous solution as well as in ethanol. The effect of certain proteins on
the rate of aspirin hydrolysis will also be examined. The data will be combined to
construct a hydrolysis profile to calculate the rate constant of hydrolysis.

Theoretical

The rate equation for the hydrolysis of aspirin is complex but at a given pH in
dilute aqueous solution the equation reduces to the first-order equation shown in (1), in
which [ASA] is the aspirin concentration at time t and k is the rate constant.

d ( ASA)
             k ( ASA)                              Equation 1
dt

The integrated forms of this equation are shown in (2) and (3), in which (ASA)0 is the
aspirin concentration at time 0, and (ASA) is the concentration remaining at time t.

ln ( ASA)  ln ( ASA) o  kt                         Equation 2

( ASA)  ( ASA) o e  kt                             Equation 3

The rate constant can be determined by measuring the concentration of aspirin as a
function of time. In this experiment k will be measured in different solvents and in the
presence or the absence of Albumin and/or lens proteins.

Analytical Procedure

1
As described below, this experiment will be conducted preparing a 100 mg%
(i.e., 100 mg/100 mL or 0.00556 M) solution of aspirin in buffer. Although we wish to
measure the concentration of aspirin in the solution it is more convenient to assay for
the hydrolysis product, salicylic acid (SA). Each mole of ASA that degrades produces 1
mole of SA:

( ASA) deg raded  0.00556  ( ASA)  ( SA)                   Equation 4

where the concentrations are expressed as molar concentration.

The SA is measured colorimetrically in a Spectronic 20 colorimeter at 540 nm as
a purple complex formed with ferric nitrate. The ferric nitrate reagent contains 4 g of
ferric nitrate (Fe(NO3)3.9H2O) and 12 ml 1N HCl in 100 ml of solution. The Beer's Law
relationship may be expressed as follows:
(SA)  0.00304 Abs                                            Equation 5
when the analytical procedure is carried out as described below.

Thus, the concentration of ASA present at any time may be determined from the
following equation:
( ASA)  0.00556  0.00304 Abs                                Equation 6
Group Instructions
thermometer
1.    Each group (3-4 students) will be
assigned a temperature and a pH at                            ASA Solution
which to study the hydrolysis of ASA.

2.    Buffer solutions are provided. Measure
out approximately 100 mL of the
appropriate buffer into a flask. Place a
thermometer in the flask and place the
hotplate to maximum heating until the                                    heating
o
solution reaches within about 10 C of the                                indicator
target temperature, and then adjust the
thermostat until the indicator light goes
out. Allow the solution to warm to the
experimental temperature before proceeding; if you overshoot the temperature,
remove the flask from the hotplate temporarily. The solution must be maintained
at the assigned temperature  2 oC throughout the reaction period.
3.    Weigh a 100 mg quantity of the ASA powder to prepare 100 mL of a 100 mg%
solution (100 mg/100 mL). Add this quantity of ASA to the warm buffer solution
and agitate gently until the solid has completely dissolved. The solid ASA must
be completely dissolved before any measurements are made.

2
4.    Pipette 5 ml of the ferric nitrate reagent directly into a Spectronic cuvette.
Withdraw 1 mL from the ASA solution and pipette it directly into the cuvette
containing the color reagent. Mix completely and measure the absorbance (Abs)
of the solution at 540 nm. Record the time and absorbance reading on your data
sheet. The first reading will represent "time 0" although it is likely that some

5.    Using Equation (6) convert the Abs values to ASA concentration at that time.

6.    Continue with steps 4 and 5 at 5-10 min intervals for a period of at least 60
minutes.

7.    Compute the apparent first-order rate constant from the plot of ln [ASA] versus t.
Report your data to the instructor before leaving the laboratory. The entire
class data will be needed to answer some of the Analysis of Data questions.

Analysis of Data:
Your group will need to submit a report, in the format used for the workshops, that

1.    a.     Is your plot of ln [ASA] versus t consistent with an apparent first-order
reaction?

b.     From your data, calculate the half-life and T90.

2.    Use the class data to:

a.     Prepare an Arrhenius plot for the hydrolysis of aspirin at your pH.

b.     Calculate the activation energy at this pH.

c.     Predict the shelf-life of your aspirin solution at 0oC, assuming 10%

3.    Use the class data to:

a.     Prepare a log k-pH profile at two temperatures.

b.     At what pH would you buffer an aqueous solution of aspirin for maximum
stability?

c.      Is the pH for maximum stability temperature dependent?

3

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