Kinetics of Hydrolysis of Aspirin - Assignment Example

Kinetics of Hydrolysis of Аsрirin Students name: University Abstract The hydrolysis of aspirin is an ester hydrolysis. The reaction may be both catalysed by an acid and a base. As a result, this will give rise to a composite rate law. Composite rate law is a summation of rate constant for base catalysed reactions, acid catalysed reactions and rate constants for un-catalysed reactions. The hydrolysis products of aspirin are salicylic acid and acetic acid. The maximum absorbance of salicylic acid is 295nm but aspirin does not absorb at this specific wavelength. The various properties of these reactions are monitored with increase in wavelength. Several drugs with simultaneous consumption of alcohol or ethanol are not advised. The main purpose of ethanol in this experiment is to ensure that salicylic acid is solubilised. Introduction The hydrolysis of aspirin to its active form, salicyclic acid, occurs much more rapidly in base than in acid. This illustrates a very important principle – that drug stability and drug action are often strongly dependent on the different pH conditions of the body. In this experiment, the hydrolysis of aspirin will be studied quantitatively under basic conditions Theory Many drugs have some degree of acid or base character. Therefore, the pH of the environment they are in may affect such things as solubility, uptake, activity and stability. This is especially true for drugs which are administered orally since there is a marked change in pH from the stomach (pH 1.5) to the small intestine (pH 8). Aspirin, or acetylsalicylic acid, is the acid ester of salicyclic acid. In general, the hydrolysis of esters may be catalysed by either acid or base. The precise details of the mechanism of hydrolysis reactions have been the subject of an enormous research effort, since they are of such fundamental importance. The generally accepted mechanisms of acid- and base- catalysed hydrolysis are known; however, many researchers particularly in the biotechnology industry are applying this fundamental knowledge in new and more complicated systems. In this experiment, the hydrolysis of aspirin will be studied under pseudo-order conditions. This will allow the order with respect to aspirin concentration to be determined. The order with respect to the concentration of hydroxide ions will be given and from this data you will be asked to draw conclusions about the mechanism. The effect of alcohol on the hydrolysis kinetics will also be studied. Equipment used 1 cm UV absorption cell, UV spectrophotometer, Start timer, 50 mL volumetric flask, Pipette, small beaker, weighing balance and a spectrometer. Chemicals used 5 * 10-3 M solution of salicylic acid, 5 *10-3 M NaOH, 20% ethanol, 5 * 10-4 M solution of acetylsalicylic acid. Description of the experiment procedure 50 mL of a 5 * 10-3 M solution of salicylic acid (2-HOC6H4CO2H) in 20% ethanol and approx. 5 * 10-3 M NaOH was prepared as follows: The required amount of salicylic acid (molar mass 138.1 g mol-1) was weighed in a Small beaker on an accurate (4 figure) balance and dissolved in 10 mL of ethanol and transferred to a 50 mL volumetric flask using the stock NaOH solution. 50 mL of a 5 * 10-4 M solution of salicylic acid was prepared as follows: 10 mL of ethanol was placed in a 50 mL volumetric flask. Using pipette, required volume of 5 * 10-3 M solution was transferred to make a 1 in 10 dilution. It was later made up to mark with stock NaOH solution. 50 mL of a 5 * 10-4 M solution of acetylsalicylic acid (2-CH3CO2C6H4CO2H) was prepared as described above. Absorbance of salicylic acid was measured at 295 nm. This value (Ao) was used be in subsequent calculations. Acetylsalicylic acid was placed in water bath at 37 °C. Timer and UV spectrophotometer were started after the solution was placed in the bath. After 5 min some of the acetylsalicylic acid solution was transferred to 1 cm UV absorption cell, placed in the heated cell holder and absorbance measured at 295 nm. Absorbance was read every 5 minutes until 60 minutes elapsed. Results time (s) Absorbance (AU) 1.4 0.162305 62 0.174727 122 0.181601 182 0.194678 242 0.206861 302 0.218022 362 0.229435 422 0.237493 482 0.247564 542 0.255919 602 0.266902 662 0.274701 722 0.283675 782 0.292154 842 0.299869 902 0.305558 962 0.312027 1022 0.317026 1082 0.323942 1142 0.332082 1201.9 0.337603 1261.9 0.342622 1321.9 0.34824 1381.9 0.353421 1441.9 0.362477 1501.9 0.364834 1561.9 0.368964 1621.9 0.372244 1681.9 0.378593 1741.9 0.383067 1801.9 0.384329 1861.9 0.391102 1921.9 0.395436 1981.9 0.396713 2041.9 0.398689 2101.9 0.402884 2161.9 0.404442 2221.9 0.407774 2281.9 0.408778 2341.9 0.416675 2401.9 0.415487 CALCULATIONS Beer-Lambert’s Law was used; A=εlc, where A is absorbance, C is the concentration and L is the length of cuvette across the wall. C = 0 .415487/3470 = 1.3109 * 10 -4 M From the plot of graphs, we found the order of reaction as two because the graphs did not produce a straight line. Straight line graphs are only for first order reactions. Hydrolysis of aspirin is pseudo-first order. Pseudo-order rate constant is equal to negative slope of a plot of In (ester) verses time. It was 2333.3333. Half-life of the reaction is time needed for half of the reactant to be depleted. Half-life of reaction was found to be 300 seconds and the reaction was allowed to run for 8 half-lifes. This reaction follows first-order kinetics. To calculate the rate constant for the base-catalyzed hydrolysis, the absorbance of the reactant is needed, there was a 1:1 stoichiometric ratio between aspirin and salicylic acid. The amount of aspirin plus the amount of salicylate is constant. This gives the relationship: [aspirin] t=0= [salicylate] t=∞= [aspirin] t+ [salicylate] t. Another relationship between the two concentrations is [aspirin] t= [salicylate] t=∞ - [salicylate] t. Because this reaction only depends on the concentration of one reactant (aspirin), it obeys first-order kinetics, A = exp (-b t) + c Where, A= [salicylate] t=∞; b=k, the first-order rate constant. A semi-log plot of the aspirin concentration remaining versus time should yield a straight line with a negative slope equal to –K. Having found the value of –k, you fix it in the equations since the concentration of substances are known. The rate determining step is the step number two. It is a highly ordered transition state whose structure resembles the products of the reaction being considered. 3.0 kobs = k [OH–]n ln (Ao - A ) =-kt -k = ln (Ao - A) / t = -1.12719/ 1082 = 0.00104 s-1 The calculated value of K is less than that obtained graphically. The concentration percentage of alcohol in hydrolysis solution is 20%. Alcohol increases the rate of hydrolysis because aspirin freely soluble in and partially soluble in water. The hydrolysis of aspirin (acetylsalicylic acid) takes place in the stomach and the blood. Discussion The objectives of the experiment were achieved. A base-catalyst is seen to quicken the hydrolysis of aspirin. Using the spectrophotometer and since this is a first-order reaction, the rate constant for the base-catalyzed hydrolysis of aspirin was determined. Kobs was determined graphically and also the half- life of the reactions were determined too. References: Jones PW, J Phys Chem, (1977), 45, 345. Garrett, E. R. J. Am. Chem. Soc. 1957, 79, 3401. Read More