1

CHEMISTRY

SCHOOL OF ENGINEERING & PHYSICAL SCIENCES

YEAR 3 PRACTICAL ORGANIC CHEMISTRY

Computational Experiment HyperChem Manual

Please return instructions to WP111 at the end of the lab session

2 Introduction HyperChem is a computational chemistry package. It allows you to build chemical structures, then manipulate and analyse them using theoretical chemistry. This guide outlines the basic principles of how to use HyperChem. Throughout, it is important to make sure that the results you are being given make some sort of chemical sense. If a calculation informs you that half of the atoms in an organic molecule have a +3 charge and the other half a -3 charge, something has clearly gone wrong. Computational methods are approximations, so this can happen. Simply try again, and if you have further difficulty, ask for assistance from a demonstrator. Starting HyperChem HyperChem is currently available on the computers in WP1.02. Load HyperChem from the Start menu All Programs folder as follows:

 

3 Configuring HyperChem

Open the “File” menu and choose “Preferences”. Change the “Window Color” to white. This will save toner/ink when you print your report.

Open the “Display” menu and choose “Element Color…”. Select “Hydrogen” on the left and change its color to black on the right.

4 By default, HyperChem limits the number of bonds each atom can have according to some well-intentioned but restrictive rules. This can cause difficulty in drawing certain intermediates (e.g. carbocations) and transition states. To stop this, go to the “Build” menu and tick “Allow Arbitrary Valence”.

HyperChem should remember your default settings for your next session. Working with HyperChem Structures you build can be saved and loaded using the File menu as in any other piece of software. You should save each structure before performing a calculation. To take a picture of the screen contents, press PrintScrn on your keyboard.1 The picture is copied to your clipboard. In Paint or any other picture-editing program, crop the image to size, then finally paste into your Word report. Working in HyperChem involves three basic steps: 1) Creating molecules. Drawing the structure, and making a 3D model. 2) Optimising that structure. Finding its preferred shape with a computational method. 3) Calculating the properties of that molecule, to answer a chemical question.

1 HyperChem suggests the use of the F9 key to take screenshots. However, this does not always work and, after a while, only copies blank images into the clipboard. To be on the safe side press the Print Screen key on the top right hand side of the keyboard instead.

5

1. Building molecules

Molecules are drawn using the “Draw” tool :

Single-click on this icon to activate the tool. The pointer changes to indicate the active tool.

Left click anywhere in the window to create an atom. Right click on an atom to delete that atom.

To use a different element, double-click the draw icon. This will display a periodic table where you can double-click on the element you wish to use. Quick buttons have been provided for switching to C, N, and O on the toolbar.

To change an existing atom to a different element, activate a different element and click on it. The atom will change.

To create a bond, either:

Create two atoms, and then drag between them with the left mouse button, or Create an atom, then drag from that atom with the left mouse button. A new atom will be

created and bonded to the first atom when you release the left mouse button. To increase bond order (to make double or triple bonds), left-click on the bond. To decrease bond order, right-click on the bond. To create an aromatic ring, double-click on any one of the bonds in the ring.

You do not need to draw hydrogens. These will be added automatically when you Build the structure.

If you want to change the charge on an atom, select it (see the section on Selecting in chapter 2. Conformations) and choose “Set Formal Charge” in the Build menu.

Once you have drawn a molecule, it must be changed into a 3D model. To do this, click the “Model

Builder” icon on the toolbar. Alternatively, open the “Build” menu and choose “Add H and model build”. The program will then convert your drawing drawing into a 3D model, add hydrogens, and set bond lengths and angles according to basic rules. You can still edit the molecule after building. When you are drawing charged intermediates, HyperChem may add extra hydrogens that you didn’t intend. Simply delete these.

6

Manipulations

Structures can be manipulated with the translate and rotate tools in the toolbar:

If you use the left button, you move your virtual “camera”. If you use the right button, you will move the selected object(s).

The “zoom” tool is useful when building large structures. Hold the left mouse button and move the mouse up or down to zoom in or out. Performing optimisations The “geometry optimisation” takes the approximate 3D model generated by the “Build” command, and adjusts the positions of the atoms to lower the energy of the structure, making it more stable. This is repeated until changes in the structure only have a small effect on the energy. The structure can be said to be at a “minimum” in energy. For example, for an H-F molecule, this will set the bond length to its optimum value. First, use the “Setup” menu to tell the computer what physical model to use in the optimisation. This should be Semi-empirical for most of the calculations. We will use an AM1 parameter set. This performs an inaccurate but fast calculation. Select “AM1” and click “OK”.

7

Next, go to the Compute menu and instruct the computer to perform a Geometry Optimisation.

Use a Polak-Ribiere (“conjugate gradient”) algorithm for optimisations with an RMS gradient condition of 0.01 kcal/(Å mol). The status line at the bottom of the screen will display CONV=YES when the optimisation is complete. If it states CONV=NO, repeat the optimisation.

8 Displaying molecules (rendering) Familiarise yourself with the various rendering options. The simplest is the Sticks model (below left) and resembles mostly a line drawing of the molecular structure. Rendering atoms as Balls (below right) reflects the size of each atom and shows how much space is occupied.

The Balls and Cylinders (below left) and Tubes model (below right) are a compromise between the extremes. Which one you use tends to be down to personal preferences.

9

2. Conformations A potential energy surface is a plot of how the energy of the molecule varies with some parameter, which is chosen by selecting several atoms. For example, if you choose two atoms, you can plot how the energy changes as you vary the distance between them. Your potential energy surface calculations should be performed using the Semi-empirical method with the AM1 parameter set. Perform a Geometry Optimisation first. A torsional potential energy surface is obtained by first selecting the four atoms in the torsion (rotation), and then instruct HyperChem to rotate the molecule around the bond between the second and third atoms, varying the angle between the first and last atoms. Watch the molecule during the scan to see exactly what rotation you are studying.

Selecting atoms Selecting parts of your structures performs actions only on your selection. For example, if you select an atom and choose “Set Formal Charge”, then only the charge on that atom is changed. The

select tool has this icon . A left click with the select tool selects an atom or bond under the pointer. This colours the selected atom, bond, molecule etc. green. A right click with the select tool deselects atoms or bonds under the pointer. Clicking on the background selects or deselects everything. To select a large area, hold both mouse buttons and drag the mouse. Selecting or deselecting two atoms is equivalent to selecting the bond between them, and vice versa. If you wish to select multiple atoms for calculating torsional energies:

Go to the Select menu and tick “Multiple Selections”, because this allows several atoms or molecules to be selected at the same time.

2

3

1

4

10

Press the SHIFT key and left-click on all 4 atoms making up the torsion angle, then release

the SHIFT key. Now perform a potential energy surface calculation choosing “Potential” in the Compute menu.

Be sure to set the plot to cover a Bond Angle of 0° to 360°, then click “OK”. HyperChem may refuse to calculate the PES if you have cancelled a previous calculation. If this happens, save your molecule, exit and reopen HyperChem, re-load your molecule, and start again.

To copy the plot of the potential energy surface to the clipboard so that you can paste it into your results, click “Properties”, the “System” tab, set Format to BMP, set Target to Clipboard and finally click Copy. To save the plot, set Target to File, and then Browse to a folder and give the image a name, then click Save.

11

Tick Save Data, enter a filename and select Graph, then press Save. This will save the energy values (in kcal/mol) and angles into a text file.

The gsp file created by HyperChem can be opened with Excel. Your data is delimited. Start importing at row 27 (starting with "GraphData="). When asked about delimiters, tick Other and enter ~ (press ALT and, while keeping this key pressed, type 126 on the numeric keypad).

12

Your data will end up in two rows. Select the rows containing the relevant data and copy, then use Paste Special and tick Transpose to paste the data into column format suitable for creating a plot.

13

3. Frontier molecular orbitals Viewing orbitals You can view the Orbitals that the electrons reside in by choosing “Orbitals” in the “Compute” menu after performing a single point ab initio or a semi-empirical MO calculation. Drag the window to one side so you can see the molecule. To view the HOMO, click the HOMO- button and set the number in the box to “0”, then click Plot. To view the LUMO, click the LUMO+ button and set the number in the box to “0”, then click Plot. If you press OK to dismiss the window, you can manipulate the orbital using the tools described in Section 1. Use the 3D isosurface view for your results.

The Options button provides several settings for changing the appearance of the orbital. In particular, under Isosurface Rendering you should make the orbitals transparent so that the molecule is visible underneath. Under Isosurface Grid, change the “Grid Mesh size” to “medium” to make more attractive orbital plots, although these will take longer to render than the default “coarse”. The “Orbital Contour Value” setting changes the size of the molecular orbital. Decreasing this number produces larger orbitals. Set this value to 0.02.

14

Frontier molecular orbital energies Make sure that you minimise the molecule at PM3 level.

The Orbitals menu also shows the energy of the orbital (in electron volts). Select the HOMO- button and enter "0" in the box, then make a note of the Energy. For the LUMO, select the LUMO+ button and change the number in the box to “0”, then note the Energy value.

You can zoom in here

15

4. Diels-Alder reaction Heat of formation You can view the Heat of formation by choosing “Properties” in the “Compute” menu after performing a semi-empirical calculation.

Click on Details next to Total Energy and make a note of the Heat of Formation in the new box.

16

5. Wagner-Meerwein rearrangements Setting formal charges To set a formal charge on a C, N or O atom:

Build a molecule. Optimise the geometry, but don't carry out an ab initio calculation yet.

Use the select tool and click on the relevant atom to select it. Open the “Build” menu and choose “Set Formal Charge”, then select “+1 - Singly

Positive”.

Invoke the model builder . HyperChem has the habit of adding extra hydrogens that you didn’t intend. Simply delete these. It should be obvious to a trained chemist which hydrogens are superfluous.

Delete extra H

CH H

CHH

H

17 Glossary “Molecular mechanics” determines the energy of a chemical structure (an arrangement of atoms and bonds) using classical mechanics. The energy is defined in terms of the geometry of the molecule. A “force field” describes the variation of the energy as the atoms are moved and the bonds stretch, bend, and rotate. (Compare this to the definition of a potential energy surface.) This is quick to calculate, but inaccurate, cannot account for changes in bonding, and provides no information on the electronic structure of the system.

An electronic structure method attempts to use quantum mechanics to find the energy of the chemical system (an arrangement of nuclei) with respect to the positions of the electrons. By minimising this energy, the “real” electronic structure of the system can be found and observed. The electrons are free to move, and therefore bonds of all types can be broken and formed in an electronic structure method. Important properties can be determined such as NMR (by calculating the shielding of the nuclei by the electrons) and UV-vis spectra (by finding the energies of excited electronic states). An “ab-initio” (latin for “from the beginning”) method calculates of the energy system with respect to the positions of the electrons and nuclei, using only quantum mechanics and the known properties of the particles. This method is computationally expensive, because the equations depend on the position and the spin of every electron, plus the positions of the nuclei. However it is theoretically rigorous and can be very accurate. A semi-empirical method is similar to ab-initio, but some of the parameters used in the equations are taken from experiment instead of being calculated. Therefore this method is quicker, but depends on the experimental parameters being similar to those that would have been calculated. “Density functional theory” defines the properties of the system (such as energy) in terms of the electron density. A “functional” is simply a function which depends on another function. In this case, we create a function which describes the electron density, and all of the other functions we use are functionals of that. The method is quick, because the calculation of properties only depends on the density function, which in turn only depends on the position in space. However determining the functionals that describe each property is a theoretical challenge. All electronic structure methods use a basis set. This is a set of possible electronic orbitals that the computer can move the electrons between to try to find the best (most stable) configuration of the electrons. The more “basis functions” there are in the set, the greater the “resolution” of the calculation. Further Information For more theoretical background, Frank Jensen’s excellent Introduction to Computational Chemistry is a good starting point.

18 Single Point calculations ALWAYS perform a semi-empirical Geometry Optimisation first BEFORE you carry out a more time-consuming ab initio calculation. A single-point calculation calculates the energy of your molecule. Use the Ab initio method, with a Small 3-21G Basis Set (click “Apply Basis Set”).

Before carrying out an ab initio calculation, check the settings under Setup -> Ab initio -> Advanced options -> MO initial guess and make sure that "Projected Hückel" is ticked. (If not, the electron density map will produce nonsense charge values such as a carbon with a +14 charge or an oxygen with a –8 charge).

19 Once the method is set up, perform the Single Point calculation. Open the “Compute” menu and select “Single Point”.

When the calculation is finished, the energy is displayed at the bottom of the screen. Pay attention to the sign: an energy of -100 is lower than an energy of -50. Ab initio also calculates the charges on the atoms, which you can view with the Display menu as described above.

If you receive an error about atoms without basis functions, this means that you have attempted to perform the calculation with only part of the molecule selected. Make sure that either nothing is selected or the whole molecule is selected, choose Ab Initio again, and click Apply Basis Set. An ab initio single point calculation generates the electronic structure of the molecule. This structure can be visualised as orbitals and electrostatic potential maps.