To evaluate the acid hydrolysis of the ester methyl acetate (due to its fast rate of hydrolysis hence enabling you to see quick results. The principle of what happens to methyl acetate is the same as what might happen for an ester drug, however for drugs the process of hydrolysis could be much longer (i.e. months or even years).
Introduction
Drugs may be decomposed by a number of routes including hydrolysis, oxidation or polymerisation. Many drugs are esters or amides and therefore are susceptible to hydrolysis which might be catalysed by hydrogen ions (acid catalysis) or hydroxyl ions (base catalysis) (Equation 1.1).
Ester compoundCarboxylic acidAlcohol
Equation.1.1. Ester hydrolysis in an aqueous environment.
The rate of hydrolysis of many susceptible drugs is likely to follow first order kinetics (i.e. being dependent on the concentration of the material which hydrolyses):
Rate d(C0 - Ct ) dCt
kC
dt
where:
co is the initial drug concentration
ct is the drug concentration at time t k is the hydrolysis rate constant
dtt
integration, the following equation is produced:
2.303 log C0
log C
log C kt
kCt
t02.303
A plot of Log Ct against t should produce a straight line (Fig.1.1).
Fig.1.1. A first order reaction showing the remaining amount of active against time.
During the hydrolysis of methyl acetate, acetic acid is produced (Equation.1.2). CH3COOCH3+H2O+H+CH3COOH+CH3OH+H+
Methyl acetate
Water
Acetic acid
Methanol
Equation 1.2. Acid-catalysed hydrolysis of methyl acetate.
The resultant acid can be quantified by titration with an appropriate base such as sodium hydroxide (NaOH) (Equation 4.3):
NaOH+HCl→NaCl+H2O
Sodium hydroxide
Hydrochloric acid
Sodium chloride
Water
Equation 1.3. A typical equation for acid-based titration. IMPORTANT
Lab coats, safety glasses and gloves should be worn at all times.
Experimental Method
Ask for help/advice if youare unsure about any of the experimental procedures.
You have four thermostatic water baths set up at room temperature, 35°C, 45°C, 55°C.
In a clean 250 ml Erlenmeyer (conical) flask, place 50 ml HCl (0.2 M) using a pipette.
Add water (45 ml) and properly mix with the acid. Place the flask in the specified water bath and leave for 10 min to equilibrate.
Pipette methyl acetate (5 ml) (MW 74 g/mol; density 0.934 g/ml) into the flask and mix rapidly. Start counting the time using a stop watch. Immediately take 5 ml of the mixture using a clean pipette (not the one you used before) and place it in a conical flask containing 45 ml deionised water.
Titrate the contents immediately and accurately with NaOH (0.2 M) using phenolphthalein as an end-point indicator.
Repeat this procedure in the following time intervals: 10, 20, 30, 40 and 50 min using clean flasks containing 45 ml deionised water. Remember that the original flask must be immersed in the water bath all the time.
Results:
From the titration data, calculate the concentration of acids in the solutions and so the concentration of residual ester.
To do this:
Calculate the initial concentration C0 of methyl acetate.
Calculate Moles of acetic acid reacted. Remember: this is = moles of NaOH.
Calculate the Moles of acetic acid at different titration times.
0 minutes only HCl is present. Between 10 minutes and 50 minutes, both HCL and acetic acid are present. Hydrochloric acid remains constant for all titration samples, therefore moles of acetic acid at 0 minutes minus the moles of acetic acid reacted at different temperatures equals the moles of acetic acid.
Calculate the concentration of acetic acid at different titration times:
Concentration of acetic acid (M) Moles of acetic acid (moles)
Volume (L)
Calculate the concentrations of methyl acetate (Ch) hydrolysed at different times. Remember: there is a 1:1 mole ratio.
Calculate the concentration of methyl acetate (Ct) remaining at different times.
