Chemistry 344 Molecular Modeling Spring 2006

Transcription

1 1 Chemistry 344 Molecular Modeling Spring Introduction to Molecular Modeling 1.2 Problem Set A: Using Molecular Mechanics Calculations to Analyze Conformations of Hydrocarbons Butane Substituted cyclohexanes 1.3 Problem Set B: Using M Calculations to Understand Electron Distribution within Molecules Valence Bond Theory and VSEPR Models Compared with M Theory Formal charges and charge distribution Ms for hydrocarbons. 1.4 Problem Set C: S N 1 and S N 2 reactivity S N 2 reactivity by calculating transition states for RCl + Cl S N 1 reactivity by calculating the relative reaction energies for carbocation formation. 1.5 Problem Set D: EAS Reactivity Predicting Regiochemistry of Reactions Predictions based on partial charges in aromatic starting materials Predictions based on energies of arenium ion intermediates 1.6 Problem Set E: Diels-Alder Reactions Rationalization of relative reaction rates based on HM-LUM gap Prediction of stereochemistry based on transition state energies

2 2 1.1 Introduction to Molecular Modeling Molecular Modeling is a general term that can refer to a wide range of activities, from constructing ball and stick models of molecules to doing sophisticated computational modeling carried out on computers. Computational modeling has been developed into a set of extremely powerful tools that can accurately predict detailed molecular structures and calculate relative energies of compounds. Computational modeling generally falls into two categories: 1) molecular mechanics (MM) models that are based on force field calculations. They specify best distance, angle, and dihedral angle prescriptions for various types of atoms and bonding situations, and employ simple formulae for how the energy increases when structural requirements alter these parameters. MM calculations are extremely fast and can be done on almost any sized molecule. 2) quantum chemical models that are based on approximating solutions to the Schrödinger equation. These are usually called molecular orbital (M) calculations, and vary widely in their degree of sophistication and computer memory/time required. M calculations are far more general than MM calculations, which fail (often miserably) when structures are calculated that lie outside the range for which the force field parameters apply. The enormous advancement in speed and memory capacity of desktop computers, combined with innovations in molecular modeling software, have made M calculations a practical everyday modeling tool for use in predicting detailed structures of compounds (including lowest energy conformations), predicting the most likely products of reactions, and rationalizing reactions and mechanisms. The calculations are not limited to stable molecules; they can also be used to calculate the structures and energies of reactive intermediates and transition states. 1.2 Problem Set A: Using Molecular Mechanics Calculations to Analyze Conformations of Hydrocarbons. As an introduction to using the Spartan ST modeling program, you will first calculate some structures that relate to conformations. Conformations of hydrocarbons are obtained more accurately using molecular mechanics than all but the highest level of M calculations. The MM programs have been specially parameterized to generate correct results for hydrocarbons. In the exercises that follow, we will first use MM calculations to analyze conformations of some simple hydrocarbons and then in the subsequent exercises we will move to semi-empirical M calculations to evaluate the electronic structure and energies of more complex molecules, using the data to make predictions of reactivity Butane (Do this as an individual exercise, and discuss it with your partner.) Upon opening Spartan ST, a window with the words and icons shown below appears. blue bar commands (black) icons in quotes Click on File New, and the model kit panel shown at right will appear at the right of the window. Click on File Save As, name it [type in butane or whatever] and save the

3 3 file. With the rganic tab selected as shown at right, the program allows you to add individual atoms (by clicking on one of the 20 choices on the array below the window; the atom or group that will be added upon clicking on the drawing screen appears in the window. (For example, the C(sp 3 ) has been selected in the panel shown at right.) ne may also select pre-drawn Groups or Rings (below the array) to add, by picking one from the list that appears upon clicking on the symbol to the right of each. Whatever is displayed in the window panel at the top will be added when you click on the drawing screen. To make butane, you only need the C(sp 3 ). When you click once, the C appears on the screen with four yellow free valences coming off tetrahedrally. Clicking at the end of a free valence will add whatever is shown in the window onto the structure that you are drawing. The structure can be rotated by holding the left mouse button down and moving the cursor. The structure can be moved (translated) around the screen by holding the right mouse button down and moving the cursor. When in structure-building mode (i.e. when the model kit is open, rotation about single bonds can be done by clicking on the bond holding down the Alt key and the left mouse button and moving the cursor. Note: clicking on the E icon does a quick molecular mechanics optimization of whatever structure is on the screen. This can be very useful to shape up structures while you are building them. Make anti butane by clicking on the proper free valences. If you make a mistake you can either undo it if you click on Edit Undo (or control-z) before you do anything else, or erase desired atoms or valences clicking the on the menu bar and then clicking the atom to be erased. (careful! This eraser stays on until you push the + to turn it off!). You can only add to your structure when yellow free valences are on the screen; pressing most icons finishes your drawing: the bonds turn silver, and white hydrogens appear on all of the free valences. You can get back in drawing mode by clicking on + on the menu bar. For closely related calculations it is useful to keep them in the same file. Click on File and New Molecule to get a blank screen (the other drawing is still in the file). Draw gauche butane on it. You can toggle back and forth between the two butane conformers by using the buttons at the lower left of the screen. Display Spreadsheet has the molecules in your file listed on it. Do MM calculations on them using Setup Calculations. Select Equilibrium Geometry and Molecular Mechanics using the symbols, and finally, click on Submit. Both molecules will be calculated (all molecules in a file are calculated (or recalculated) upon clicking submit (which is a reason not to have very many in the same file unless you need to directly compare them). The energies calculated may be most easily viewed using Display Spreadsheet, clicking at the top of

4 4 the 2 nd column, and Add..., highlighting E and rel. E, selecting kj/mol. Throughout all of the modeling exercises, use kj/mole as the energy units and record all calculated energy values in your lab notebook. You can obtain geometrical information on your optimized structures as follows: Bond distances will appear at the bottom of the screen when you click on a bond or when you click? followed by clicking the atoms at either end of the bond. Similarly, bond angles and dihedral angles can be displayed by clicking? or \?\ and the appropriate atoms. For each of these functions, after clicking on 2 (or a bond), 3, or 4 atoms (in order), the current value appears in the box. Any of the values can be changed by typing a new value in the display box. ne important thing to know about Spartan ST is that it will not lower the symmetry of the structure you enter, even if the energy would be lower. To test this, build the highest energy eclipsed conformer of butane as a new molecule added to your file that contains anti and gauche butane. Make sure the eclipsed butane is perfectly symmetrical by stating with ethane setting the H-C-C-H dihedral angle to zero, and then adding two more methyls so they are eclipsed. Resubmit the calculation using molecular mechanics again. If the program was allowed to lower the symmetry of the eclipsed butane, it would optimize the structure by converting it to staggered butane. Did this happen? Can you see any advantage to the constraint that the program will not lower the symmetry of the structure that you enter? Another constraint of this program is that it will only optimize your structure by continuously lowering the energy. The program will not take your structure over even small activation barriers in arriving at the optimized structure. When the structure being calculated is not locked in a high symmetry state, the program is designed to crawl downhill from the starting point until the energy stops changing. From your calculations on butane conformers, can you see any advantage to the constraint that the program does not overcome energy barriers in optimizing your structure? 1. Taking the calculated energy of anti butane as the zero reference, compare the relative energies of anti, gauche, and eclipsed butane. How well do these agree with the reference values given on page 158 in Solomons 8 th ed? (p. 153 in 7 th ed.) 2. What are the practical advantages of the symmetry and activation barrier constraints of Spartan ST discussed above? Note: Throughout these exercises, the files for all molecules on the screen need to be closed before starting on the next exercise Substituted cyclohexanes (Do this as a shared exercise with your partner.) The cyclohexane molecule can be selected, preformed, from the model kit using the Rings menu. Add a methyl group to one of the equatorial positions and save the file with an appropriate file name for retrieval later. Click on File, New Molecule and build axial methylcyclohexane as well. Using molecular mechanics, calculate the equilibrium

5 5 geometries and energies of the two molecules. Record the energy values and relative energy (energy difference) in your lab notebook. In a separate file, build axial and equatorial tert-butylcyclohexane and calculate their energies. In another separate file, build the three possible stereoisomers of 1,3-dimethylcyclohexane and calculate their equilibrium geometries and energies. Finally, build and calculate all-equatorial and allaxial hexaisopropylcyclohexane (advice: for all-equatorial, put the groups on a few at a time and use E to order the structure before adding the rest). 1. Compare the energy differences you obtained between equatorial and axial isomers of methylcylohexane and t-butylcyclohexane. How well do these energy differences agree with the reference values given on page of Solomons? (p in 7 th ed.) 2. List the stereoisomers of 1,3-dimethylcyclohexane in order of increasing energy based on the energy values you calculated. 3. Are the relative energies of the hexaisopropylcyclohexane conformers consistent with your expectations? Provide a rationale for the result. 1.3 Problem Set B: Using M Calculations to Understand Electron Distribution Within Molecules Formal charges and charge distribution. (Do this as an individual exercise and discuss it with your partner.) You have been taught to write formal charges on valence bond (VB) structures, for example, the central atoms of NH 4 + and H 3 + have a +1 charge. Formal charges are useful in keeping track of bonding and non-bonding electrons and predicting/remembering how nucleophiles and electrophiles behave, but they are basically just a (very powerful) bookkeeping trick. The formal charges have little to do with the distribution of electrons in molecules. They are what the charge would have been if all the bonds were homopolar (that is, if the electrons in bonds between two atoms on the average were exactly half-way between them). But the electronegativities of atoms vary widely, causing the actual partial charges on atoms to be quite different from that implied by the formal charge. After calculating an optimized molecular structure for any molecule using Spartan ST, atomic charges can be displayed for each atom by clicking Display Properties followed by clicking on the atom. Unlike formal charges, these partial charges are supposed to represent the actual charge on each atom and they can be very useful in predicting reactivity.

6 6 Start a new file and create a water molecule by selecting the oxygen atom from the inorganic menu of the model kit and clicking the button below the periodic table that shows two bonds coming off of a central atom with a bent geometry (as shown in figure on page 5). As with carbon, you do not need to add the hydrogens onto the oxygen; the program will do it for you. Go to Setup Calculations, and calculate the Equilibrium Geometry and energy of the water molecule using Semi-Empirical. After running the calculation go to Display Spreadsheet and find the energy in kj/mole. Record the energy in your lab notebook. Click Display Properties and click each atom to view its partial charge. Record the charges in your lab notebook. Start a new file and build an anisole molecule. (Note: anisole is methoxybenzene.) Start with the preformed benzene ring from the model kit. Run a semi-empirical M calculation on anisole and record the energy value in your lab notebook. Look at the partial charges on the oxygen atom and each of the carbon atoms. Sketch the molecule in your lab notebook and label the atoms with their partial charges. From M calculations, Spartan ST can give a pictorial depiction of electronic charge distribution in the molecule. For the anisole molecule, select Setup Surfaces (or Display Surfaces; they open the same window) click add... and the Surface =density, Property=potential, then go to the Set-up menu on the menu bar and click Submit to generate a colored electrostatic potential map which can be viewed by clicking Display Surfaces and checking the box next to density. The picture uses color coding to indicate the charge at all points on the outer surface (Van der Waals surface) of the electron cloud of the molecule. Red indicates negative charge, and blue indicates positive charge wheras yellow and green are near neutral. These types of pictures have become very popular to depict molecules in textbooks. (Many of them appear in Solomons 8 th edition.) However, the amount of useful information one can glean from these pictures is minimal. Instead of using these pictures, we will focus on more useful information from the M calculation such as structural geometries, energy values, partial charges calculated for each atom and individual molecular orbitals. 1. Looking at the optimized structure for anisole, why does the methoxy group adopt the indicated conformation which places the methyl group in the plane of the benzene ring? This conformation is more sterically hindered than if the methyl group rotated out of the plane of the ring. What is the C--C bond angle? In valence bond terms, what is the hybridization of the oxygen atom? 2. Based on the partial charges you found for the ring carbons of anisole, which positions do you predict are most susceptible to electrophilic attack? Ms for hydrocarbons. (Do this as an individual exercise and discuss it with your partner.) ur valence bond (VB) pictures of molecules show pairs of valence electrons as lines that represent single bonds (one line for 2 electrons) double bonds (two

7 7 lines for 4 electrons) or triple bonds (three lines for six electrons). They are very simple, and their simplicity is sufficient for many purposes. Combined with the natural idea that electrons in bonds repel each other, they provide a simple rationale for the fundamental geometrical features of alkanes (nearly tetrahedral arrangement of atoms about saturated carbons), alkenes (four atoms in a plane about each C=C) and alkynes (two atoms attached linearly to C C). However, these pictures have little to do with modern theory of what leads to these geometrical features. According to M theory, the electrons are in molecular orbitals that frequently extend over the an entire molecule, and have shapes determined by the symmetry of the molecule, so valence bond depictions do not actually resemble the M picture of bonding in molecules at all. ne issue in successfully using simple bonding pictures is knowing to which situations they usefully apply. VB pictures are certainly a powerful way to consider the structures of even complex molecules in a way that can be easily understood and from which many good predictions of chemical behavior may be made. However, M pictures, while more difficult to interpret in a simple way, provide a much more accurate and realistic depiction of molecules and lead to correct answers in many cases where valence bond descriptions give incorrect answers. Spartan ST allows you to easily generate pictures of the individual Ms for molecules. They represent portions of the spatial distribution of electron density (which is the square of the wave function) with the lobes colored to indicate the sign of the wavefunction. In M theory there is generally one bonding and one antibonding M for each pair of valence electrons except for nonbonding valence electron pairs such as the lone pairs on heteroatoms that are not involved in bonding at all. nly the bonding Ms of most stable molecules are actually populated by electrons. Do a semi-empirical calculation on benzene. Select Setup Surfaces, click add... and the by Surfaces; select HM (or HM-n (after setting n), LUM, or LUM+n) and K to add a surface. Recall that these acronyms stand for for Highest ccupied M and Lowest Unoccupied M. HM-n (n = 1,2,3 ) allows you to view each of the filled orbitals below the HM in order of decreasing energy level. Add the HM and the next four filled M s (i.e. HM 1, HM 2, HM -3, HM - 4) and then go to the Set-up menu and click Submit to do the calculation. View these M s one at a time by checking the box for each one in the Surfaces window. Remember to turn one off before turning another on, or you get their sum which is only confusing. The designations of σ and π, used with valence bonds, are also used similarly to designate the symmetry of M s. For aromatic rings, the π M s are those formed by mixing various combinations of the carbon p-orbitals that are perpendicular to the ring. These M s all have a nodal plane (plane with zero electron density) in the plane of the ring. For benzene, there are three bonding and three antibonding π M s. Examine each of the filled M s you generated and classify each one as having σ or π symmetry. Also note the total number of nodes in each M.

8 8 1. What are the HM n designations of the three filled p M s in benzene? 2. Make a rough sketch of the three filled p M s of benzene showing where the nodes are. What is the relationship between the number of nodes and the energy of the M? Valence Bond Theory and VSEPR models compared with M Theory (Do this as an individual exercise and discuss it with your partner.) Most of the bonding interpretations in introductory organic chemistry use valence bond theory, and the Valence Shell Electron Pair Repulsion (VSEPR) model is often used to rationalize molecular geometries in General and rganic Chemistry textbooks. In the Solomons 8 th Ed., currently being used for Chem 343 and 345, this material is presented on p of Chapter 1. Unfortunately, these bonding descriptions are oversimplifications that are incompatible with the M picture of bonding and foster some misconceptions. Electrons certainly repel each other, but the idea that what we call lone pairs on disubstituted oxygen occur in sp 3 orbitals that are so much larger than the sp 3 orbitals represented by the CH bonds that they force the HH bond angle to contract from to 105 is certainly neither useful nor correct. Molecules assume equilibrium geometries that minimize their energy. The three atoms of H 2 must be linear or lie in a plane. If they were linear only two of the oxygen valence orbitals (one s and one p) could be involved in bonding to the hydrogens. By bending at, three of the oxygen valence orbitals can participate in bonding to the hydrogens, which lowers the energy of the molecule by mixing more p character into the H bonding orbitals. The last orbital on oxygen is the p-orbital perpendicular to the plane of the atoms. This orbital contains a pair of electrons and cannot mix at all with the s-orbitals on the hydrogens so the lone pair in this orbital is the only pair of electrons on oxygen that is strictly non-bonding. pen the H 2 file that you created earlier and generate the four filled M s. Examine each of these M s one at a time. 1. Which M contains the one lone pair on oxygen that is strictly non-bonding? 2. Do you find M s that support the view (shown on page 39 of Solomons 8 th ed.) that the oxygen in water has two identical lone pairs of electrons in sp3 orbitals? Explain. 1.4 Problem Set C: S N 1 and S N 2 reactivity In this exercise you will consider the reactivity of alkyl chlorides towards S N 1 and S N 2 reactions. Specifically, you will use M calculations to explore the relative S N 1 and S N 2 reactivity of EtCl, iprcl, tbucl, and benzyl chloride

9 Predicting S N 2 reactivity by calculating transition states for RCl + Cl - (Do this as a shared exercise with your partner.) For S N 2 reactivity, the simplest thing to do is calculate the energy of the S N 2 transition state for the attack of Cl - on the alkyl chloride, and subtract the energy of the starting reactants. That is to calculate the activation energy for the following process: RCl + Cl E RCl 2 We can use the fact that Spartan ST will not lower symmetry to generate these transition states by choosing the 5-bonded-carbon stucture from the Inorganic drawing template. This puts puts the five valences in the desired trigonal bipyramidal geometry, three planar and 120 apart (the equatorial bonds), and the other two at 90 to this plane (called the axial bonds). Add two chlorines to the valences that are at 180 to each other, and the appropriate methyl or phenyl groups to build each transition state. The equilibrium geometry semi-empirical calculation produces the S N 2 transition states (which are actually very far from the equilibrium geometry). Be sure to run the transition states as anions. Work with your lab partner to build and calculate each transition state. More than one of the TS structures can be combined in one file and the calculations run at the same time. Then build and calculate the alkyl chloride starting molecules and separately run the chloride ion. For each reaction, create a table in your lab notebook like the one below and work with your lab partner to run the calculations to fill in each table. The E aq calculation attempts to account for solvation effects and provides an estimate of how the energy of the molecule or ion would change if it was in an aqueous environment. E E aq EtCl Cl - EtCl + Cl - EtCl 2 - E = E aq = After calculating all of the activation energies, summarize them in a table like the one shown below. E E aq EtCl + Cl - iprcl + Cl - t-bucl + Cl - BzCl + Cl -

10 10 Discussion Points Briefly discuss your results in terms of consistency with your expectations for these reactions. How does solvation affect the activation energies for these reactions? How does the reactivity of benzyl chloride compare with the various alkyl chlorides? Predicting S N 1 reactivity by calculating the relative reaction energies for carbocation formation. (Do this as a shared exercise with your partner.) In the S N 2 examples above, the symmetry restrictions of Spartan ST make it easy to calculate energies of the transition states. However, in general, calculating energies of transition states (energy maxima) is more difficult and error-prone than calculating energies of molecules or ions that have some degree of stability (energy minima). For reactions that proceed through high energy intermediates such as carbocations (e.g. S N 1 reactions) we can apply the Hammond-Leffler postulate which tells us that the transition states resemble the stable species closest in energy. (See pages in Solomons 8 th ed.) Structural changes that raise the energy of the intermediates also raise the energy of the transition states, making the reactions slower. Taking advantage of this, you will analyze S N 1 reactivity by using the E s for formation of the carbocations to estimate the relative activation energies for their formation. To build the carbocations, use the inorganic tab of the model kit and select carbon with three valences in a trigonal planar geometry. Then add the appropriate methyl or phenyl groups. Work with your lab partner to build each carbocation and run a semi-empirical M calculation for the equilibrium geometry and energy. Be sure to run them as cations. More than one carbocation can be included in a file and the calculations run at the same time. For each reaction, create a table in your lab notebook like the one below and work with your lab partner to fill in each table. E E aq EtCl Cl - Et + Et + + Cl - E = E aq = After calculating all of the E s, summarize them in a table like the one shown below. E E aq EtCl iprcl t-bucl BzCl

11 11 Discussion Points Briefly discuss your results in terms of consistency with your expectations for these reactions. In general, how does solvation affect the activation energies for these reactions? How does the reactivity of benzyl chloride compare with the various alkyl chlorides? 1.5 Problem Set D: EAS Reactivity Predicting Regiochemistry of Reactions In this exercise, you will use M calculations in two different ways to predict the regiochemistry of an EAS reaction. You recently carried out the nitration of methyl benzoate in lab. You should have been able to predict the major product of the reaction using resonance arguments based on valence bond theory. Two different types of resonance arguments are commonly used to predict the regiochemistry of EAS reactions: arguments based on the resonance forms of the aromatic starting materials, and arguments based on the resonance forms of the arenium ion intermediates. Here you will carry out the corresponding M calculations and check for agreement with your predictions from valence bond resonance structures Predictions based on partial charges in aromatic starting materials. (Do this as an individual exercise and discuss it with your partner.) Use the model kit to build methyl benzoate. Run a semi-empirical calculation to determine the equilibrium geometry and energy. Check and record the partial charge at each carbon of the aromatic ring. Generate a plot of the HM of methylbenzoate by selecting Setup Surfaces, Add, HM, Submit. Note which carbons of the aromatic ring have electron density in the HM. 1. Based on the partial charges you found for the ring carbons of methyl benzoate, which positions do you predict are most susceptible to electrophilic attack? Does the result agree with valence bond resonance arguments? 2. Assuming that electrophilic attack will most likely occur by attack of the electrophile on the electron pair in the HM, can you rule out certain positions on the ring as being susceptible to electrophilic attack? Predictions based on energies of arenium ion intermediates. (Do this as a shared exercise with your partner.) The arenium ions cannot be easily made from a benzene template, so you will need to assemble them from individual carbon atoms. Use the inorganic tab of the model kit and

12 12 select carbon with three valences in a trigonal planar geometry. This provides a trivalent sp 2 carbon atom. Connect five of these sp 2 carbons together placing them at 5 out of 6 postions of a benzene ring. Now return to the model kit, click the organic tab and select a tetravalent sp 3 carbon to place in the 6th position of the benzene ring. The final bond of the ring can be closed by selecting the Make bond icon from the tool menu above the field and clicking on open valences of each carbon to form the final bond and close the ring. (This can be a little tricky and you might have to try it a couple of times to get the last bond of the ring to form.) Return to the model kit, select the electrophile (N 2 ) from the under the Groups button and bond it to the one of the open valences of the sp3 carbon of the ring. Finally, add the carboxymethyl group onto the position ortho to the sp 3 carbon. This completes the starting point structure for the arenium ion resulting from ortho attack of nitronium ion on methyl benzoate. Run a semi-empirical calculation to determine the equilibrium geometry and energy. Be sure to select Total Charge, cation before submitting the calculation. Work with your lab partner to similarly build and calculate the arenium ions resulting from meta and para attack by the nitro group. Record the calculated energies in your lab manual. 1. Based on your semi-empirical calculation, which of the arenium ions has the lowest, second lowest and highest energy? Do you notice anything surprising about any of the optimized structures? In this case the semi-empirical model does poorly. It is not parameterized very well for high energy intermediates of this type. Spartan s highest level ab initio M calculation, Hartree-Fock/6-31G* does a much better job, but it takes a couple of hours for each ion. These calculations have been run for you and you can download the results from the course website. Use the HF/6-31G* results to answer the following questions. 2. Which of the arenium ions has the lowest, second lowest and highest energy? Does the order agree with the semi-empirical result? 3. Look at the partial charges on each of the carbon atoms in each molecule. Which carbon atoms bear the greatest amount of positive charge in each cation? From the partial charges do you see evidence for the energy differences? (Hint: positive charge build-up on two adjacent atoms is destabilizing. Alternation of charge is stabilizing.) 4. What do you predict as the major mono nitration product based on the relative energies calculated for the arenium ions? Is this consistent with the result you obtained in lab? 1.6 Problem Set E: Diels-Alder Reactions Fukui was awarded the Nobel Prize in 1981 (shared with Roald Hoffmann; Woodward had died and was no longer eligible) for developing Frontier Molecular rbital (FM)

13 13 theory. The molecular orbitals of two reactants that are closest in energy to each other are usually the most important for considering reactivity, because the size of electronic interactions depend upon two factors, overlap and energy difference (electronic interactions scale with 1/ E, dropping to small values no matter what the overlap is when the energy gap gets large). Simple Diels-Alder reactions are concerted cycloadditions that have a transition state with the diene and dienophile in roughly parallel planes. In the absence of steric effects, and for similar types of diene and dienophile structures, the principal thing that affects reactivity is the smallest energy gap between diene homo and dienophile lumo, or between diene lumo and dienophile homo. The simplest prototype Diels-Alder reaction, that between ethylene and butadiene is sterically very favorable, but essentially does not occur. (The yield is under 0.01%.) The HM-LUM energy gap is too large. The reaction becomes favorable when electron-withdrawing groups are placed on the dienophile lowering the energy of the LUM. In Chem 344, we typically carry out one of the following two Diels-Alder reactions: + 2,3-dimethyl- maleic anhydride 1,2-diphenylcyclohexene- 1,3-butadiene 4,5-dicarboxylic anhydride H H H H + trans, trans-1,4- diphenylbutadiene maleic anhydride 3,6-diphenylcyclohexene- 4,5-dicarboxylic anhydride Both of these reactions occur readily and give a single product in high yield Rationalization of relative reaction rates based on HM-LUM gap (Do this as a shared exercise with your partner.) Work with your lab partner to build each of the starting molecules for each of the two reactions shown above and for ethylene and butadiene. Run a semi-empirical M calculation on each of the molecules. After running each calculation, you can view the HM and LUM energies by clicking Display Properties. These energy values are

14 14 those calculated for the specific orbitals (not the molecule). They are typically given in units of electron volts (ev). Record the HM energies of each diene and the LUM energies of each dienophile and calculate the HM-LUM differences for each reaction pair. Make a table in your lab notebook summarizing the data. Discussion Point Briefly discuss the relative HM-LUM differences for the three reactions. Are they consistent with the fact that the reaction of ethylene with butadiene is very unfavorable whereas the other two occur readily? Prediction of stereochemistry based on transition state energies (Do this as a shared exercise with your partner.) Work with your lab partner to build the two possible Diels-Alder transition states (exo and endo) for the reaction of trans,trans-1,4-diphenylbutadiene with maleic anhydride. To place the two reactant molecules on the screen together first build one, then click the Insert button at the lower right of the screen to start building the second molecule. You can click on each molecule while holding down the Ctrl key to select it and separately move or rotate it. Place the reactant molecules in about the correct position for the endo or exo reaction. Then click the Transition button, at the right end of the menu bar above the screen, and place the standard electron pushing arrows as shown below. Endo Exo To place an arrow from one bond to another, click on the first bond followed by the second bond. To place an arrow from one bond to where a new bond will be formed, click on the bond and hold down the shift key while clicking each of the two atoms that the new bond will join. (This is a little tricky. Get help from your TA if necessary.) After placing the electron pushing arrows, click the Transition button at the lower right of the screen to search the programs data base for this type of transition state. This should replace your structures with a new transition state structure with dotted lines connecting the two molecules where the new bonds will form. nce the transition state is defined, go to Setup Calculations, select Transition State Geometry, and run a semi-empirical calculation to optimize the structure and calculate the energy. Record the transition state energies for the exo and endo transition states in your lab notebook.

15 15 Separately, work with your lab partner to build the molecules for the two possible stereoisomers of the product, the one that results from the endo transition state and the one that results from the exo transition state. Use semi-empirical calculations to optimize these structures and calculate their energies. Record the energies in your lab notebook. 1. Based on the transition state energies you calculated, which stereoisomer is formed faster, the one that results from the endo transition state or the one that results from the exo transition state? 2. Based on the energies you calculated for the products, which stereoisomer is more stable? 3. Which will be the major product if the reaction is run under kinetic control? Under thermodynamic control? Based on what you learned (in Chem 343) about Diels-Alder reactions, do you expect to get the kinetic or thermodynamic product when you run the reaction in lab?