Computational Chemistry Practical Exercise 3 1 Thermodynamic vs. kinetic control Introduction The thermodynamic stability of possible products can be used to indicate the preferred product. However, even if a species is the most favoured thermodynamically, it may not dominate the yield if an alternative (less stable) product is formed more rapidly. The kinetics of a reaction are governed by the energy of the transition state. The higher (more positive) this energy is, the lower the rate of formation. The aim of this exercise is to study the sulphonation of naphthalene, as shown in Figure 1, in which a mixture of products is formed. By calculating energies of the starting material, the products and approximations of the transition states of the reactions, an assessment of the thermodynamics and kinetics of the reaction may be made, and the general approach extended to more complex species Figure 1 Sulphonation reactions of naphthalene Methods Section 1 The carbocation intermediates shown in Figure 2 can be taken as approximations of transition states. Record the enthalpies of formation of optimised geometries of the starting materials, both of the products, and both of the carbocation intermediates. When drawing your structures, double-clicking a cyclic unit is a handy short-cut to make a ring aromatic, and using the Invoke Model Builder tool will give you good starting structures to ensure the calculations do not take too long. To record the enthalpies of formation, use the following steps: – Choose the optimisation parameters using Setup -> Semi-empirical… -> PM3 -> Options -> and set charge (0 or 1) and multiplicity (1) for the molecule. – Use File -> Start Log to save a log file for the optimisation. – Start the optimisation using Compute -> Geometry Optimization… – Stop the log file using File -> Stop Log – Open the log file in a text editor, and find the line saying “Heat of Formation = “ Also remember to save your optimised structures in case you need to come back to them later on. These calculations enable a deduction of which product has the greatest thermodynamic stability and which intermediate is most rapidly formed.Computational Chemistry Practical Exercise 3 2 Figure 2 Sulphonation reactions of naphthalene showing the carbocation intermediates Section 2 Phenanthrene is a related polyaromatic hydrocarbon to naphthalene. Identify all its possible sulphonation products and predict whether there is thermodynamic or kinetic control of these reactions using computational data to support your argument. Repetitive tasks such as setting the charge, multiplicity, starting a log file, running the optimisation and opening/recording data from the log file (outlined above) can quickly get tedious. To avoid this sort of repetition in computational chemistry, it is desirable for such processes to be automated. Hyperchem uses script files for this purpose. The text below gives an example of a script file to run a semi-empirical PM3 optimisation of a neutral singlet (all electrons paired) molecule, and print the enthalpy of formation at the end of the calculation. calculation-method semi-empirical semi-empirical-method pm3 quantum-total-charge 0 multiplicity 1 do-optimization query-value heat-of-formation Frome the ELP in the folder labelled “Files for Section 2”, download the enthalpy_of_formation _neutral.scr and enthalpy_of_formation_cation.scr files. Use these scripts to optimise the geometries and determine the enthalpies of the neutral and cationic phenanthrene structures, respectively. You can run them using the Script -> Open Script command, and they should speed up the second half of this exercise significantly. SO 3H SO 3H H SO 3H H SO 3H 1-isomer 2-isomer + +Computational Chemistry Practical Exercise 3 3 Write-up The report should be a few pages long in total. Include a brief introduction outlining the background and relevance of the exercise, introducing the chemistry this exercise examines using “curly arrow” mechanisms where appropriate. A short methods section should include sufficient information for a reader to replicate the experiment. A results and discussion section should set out your main results, including tables of the energies you have determined, (qualitative) diagrams of reaction energy pathways, and interpretation of your results, being explicit about what part of your computational data supports your deductions. Make sure that all tables and figures have a number and caption. Finish with a short conclusions section outlining the significance and implications of the results, along with areas for potential future work. Questions to consider: – The sulphonation of naphthalene gives two different isomers depending on conditions. Explain this effect by comparing the stability of the products and the stability of the intermediate complexes of each isomer, remembering that heating affects only the rate of formation (the kinetics of a reaction) and not thermodynamic stability – What reasons are behind this selectivity? The answers are a combination of orbital and steric reasons. To back up any argument you propose on steric grounds, use your calculated results/structures to provide evidence for your answer. – How would the naphthalene products differ with varying reaction temperature, assuming all steps are reversible? – From your calculations on the phenanthrene molecules, which do you think will be the most favoured products at low temperature and at high temperature? Give reasons for your choices?