CHEMISTRY Organic Chemistry I Laboratory Fall 2017 Lab 4: Computer Modeling of Cyclohexane Conformations

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1 CHEMISTRY Organic Chemistry I Laboratory Fall 2017 Lab 4: Computer Modeling of Cyclohexane Conformations Purpose: You will explore how the molecular modeling software programs ChemDraw and Chem3D can be used to build cyclohexane ring conformers and evaluate their relative stability by determining Steric Energies ( G o ). These data will then be used to calculate the equilibrium constant for the ring flip interconversion of the two conformers, and the percentage of each conformer at equilibrium. Important Notes: 1) Please note that laptops are required (if possible) for this lab. You are also required to download the free ChemBioOffice software package. Bring your laptop to lab with the ChemBioOffice software already installed. 2) Your notebook will have a different structure for this lab and you will need to follow the format outlined in this handout to record all of the required information properly in your lab notebook. Follow the grading rubric at the end of the handout to ensure you earn all the points possible. 3) The software package will only fully work on a PC we will have laptops available if you have a Mac. I. Your name, the name of your lab instructor, the name of your lab partner. II. Title of the experiment and date. III. Table of Reagents. Not Required Instead, why not look up and record an inspirational quote from history. IV. Background information and notes from the pre-lab assignment. You are expected to read this lab handout, prepare this notebook section with the following content present, and review this information to prepare for a prelab quiz. Cyclohexane rings are more stable than other sizes of cycloalkanes and are more commonly found in nature. Unlike cyclopropane or cyclobutane, cyclohexane compounds are able to avoid ring strain which is comprised of angle strain and torsional strain as they are can adopt many conformations including two distinct chair conformations. The hydrogens (or groups) on the chair conformations are located in axial or equatorial positions. All of the hydrogens or groups in the axial or equatorial positons switch positions when a ring flip occurs to produce the other chair conformation. Usually the placement of a group/substituent in an equatorial position is much more stable than placing a group in an axial position. You will be testing this theory using a computational program. Preparation: Read the Solomon s text or use other resources to read about the topics below. Use this information to write a short paragraph to describe each of the following and be sure to draw structures for some of your descriptions. 1) What is cycloalkane ring strain? 2) What are cyclohexane chair conformers? 3) What is the difference between axial and equatorial positions on chair cyclohexanes? 4) How does one compare the stability of two different chair conformers for a mono-substituted cyclohexane? 5) What do the terms cis and trans represent for di-substituted cyclohexane molecules? 6) What are 1,3-diaxial interactions? Why are they de-stabilizing to a conformer? Pre-Lab Quiz: 7) You will be asked to draw simple chair conformers on the quiz in class 8) You will be asked to draw di-substituted chair conformers on the quiz in class.

2 Recitation Discussion: At the start of the actual lab period, your instructor will check your notebook and initial your pre-lab work before leading a pre-lab discussion. The two chair conformers of methyl cyclohexane will be drawn on the board and you will be shown how to use the procedure outlined in the handout to determine the relative stability of each conformer and the amount of time a molecule spends in each conformer. 9) You should record this data for methyl cyclohexane and all of your work at each step of the calculations. Keep in mind that you will then repeat this process on your own as part of your actual lab and this is will be your example. Then the two conformers of trans-1,4-di-methyl cyclohexane will be drawn on the board and you will again be shown how to use the procedure outlined in the handout to determine the relative stability of each conformer and the amount of time a molecule spends in each conformer. 10) You should record this data and each step of the calculations. Keep in mind that you will then repeat this process on your own as part of your actual lab. It will be important that you are able to replicate the work in your lab. Important Note - Section VI: You do not need to write detailed descriptions of the drawing and modeling tasks as you proceed through the laboratory experiment. However, you should record all of indicated information and be sure to show all of your calculations. Experimental Procedure: Your goal is to work with your lab partner to perform the full computational procedure on three sets of molecules: methyl cyclohexane, trans-1,4-dimethylcyclohexane, and an unknown that you will be assigned on the day of the lab. To open the ChemDraw application go to Start, Programs, ChemBioOffice, and open ChemBioDraw Ultra. Maximize the screen display. The only toolbar you will need is the Main Toolbar as shown on the right. If the Main Toolbar is not visible, you can find it under the View menu. The most important Tools for you today are circled: Lasso (allows you to select a structure or portion of a structure); Solid Bond (used to make single bonds to any atom); Eraser (lets you erase by point-and-click); Text (allows you to type headings and to type in atoms or functional groups); Cyclohexane chair 1 & 2 (lets you draw cyclohexane chair conformations). This Tutorial will help you to build methyl cyclohexane, and evaluate the relative stabilities of the axial and equatorial conformers. You will then apply this tutorial to calculate the relative stabilities of your compound. This lab assumes that you remember the basics involved in drawing chair conformations, the difference between axial and equatorial positions, and the effect of steric hindrance on chair conformer stability. To build a cyclohexane chair model, select either Cyclohexane chair 1 or 2 from the Toolbar menu, then left click anywhere on the white page; a cyclohexane chair will appear. If you want to make the chair larger or smaller, click on the Lasso tool, and your chair should be selected; if not, just Lasso the structure with your mouse. You can resize the structure by clicking and dragging any corner of the lasso box. If a dialog box appears regarding scaling, just click Yes. If you click and drag the handle sticking out the top of the lassoed structure,

3 you can rotate the structure. To remove the lasso box, just click anywhere on the white page. To add in a substituent (methyl group), select the Solid Bond tool. Left click and hold on any ring carbon, and drag to make a single bond. When you have the bond in the proper axial or equatorial orientation, release the mouse button. Repeat this on the same carbon so that you have both axial and equatorial bonds drawn. To add in a methyl group, click on the Text tool, then click on the end of either the axial or equatorial bond. Type CH3 in the text box, then hit the enter key. Repeat this with the other bond, but type H to add a hydrogen. You have now drawn a chair conformation of methyl cyclohexane. If for some reason you are not happy with the position of your axial and equatorial substituents, select the Solid Bond tool again, and holding down both the Shift and Alt keys, left click and hold on the atom or group you want to move, and drag your mouse; this allows you to change the position and bond length or any atom or substituent. Of course, you can also select the Eraser tool, and just erase a substituent and/or bond and start over. Now you are ready to move your structure into Chem3D. Select the Lasso tool, and if your entire structure is not selected, then lasso it. Go to the Edit pull down menu and select Get 3D Model. Patience! It may take seconds for Chem3D to open! You should now see a 3D model imbedded in the 2D canvas. Double click on the 3D model to open a Chem3D screen. The Chem3D toolbar should appear on the top or left of the window (the vertical orientation is shown at the right). Select the Trackball tool, then left click and hold on your model, and by dragging the mouse you can rotate and re-orient your model as you wish. Verify whether your substituent is axial or equatorial. If you don t like the ball and stick view of your model, go to the View menu---model display--- display mode---your choice (try sticks ). As you rotate your model, be sure to look down different C-C bonds to see the staggered orientation of the substituent groups. If you want to make your 3D structure larger or smaller on the screen, click on the Resize tool, then click and hold anywhere on the screen and move the mouse up (larger) or down (smaller). 11) The next step is to have Chem3D Minimize the total energy of your conformer, by making sure that the bond lengths and angles are correct, and that steric hindrance is minimized. This requires two steps. First we do a crude energy minimization by clicking the Select tool from the toolbar menu, and dragging the mouse across your model to box or lasso the entire structure (it should turn yellow). Now go to the Structure pull down menu and select Clean Up; you may notice slight changes in conformation occurring, and your structure is no longer yellow. Next, lasso the structure again, go to the Calculations pull down menu, select MM2, Minimize Energy, and click Run. Again, you may notice minor changes in the conformation of your model, which is now minimized for steric strain. At the bottom of this window you should see the calculation for Total Energy. RECORD THIS NUMBER which is the free energy (G o ) value for this particular conformer. 12) Repeat the energy minimization for the other cyclohexane conformer of your model. This is easy to do and DOES NOT require that you use ChemDraw again. Click the Text tool from the toolbar menu, and click on the substituent you wish to change. For example, if you have an equatorial CH3, click on the methyl carbon, type H in the text box, followed by Enter. The methyl group should be replaced by a hydrogen atom. Now click on the axial H, and type CH3 to add a methyl group. Now repeat step (7) to get the total energy for the second chair conformer. The value of G o for the axial methyl group (less stable) should be larger than that for the equatorial methyl group (more stable). RECORD THIS NUMBER which is the free energy (G o ) value for this particular conformer. 13) Using this information and the format below, record all of the content, calculations and results in your notebook:

4 Draw the chair templates shown below in your notebook, draw the two equilibrium ring flip chair conformers (axial and equatorial) for methyl cyclohexane. It does not matter which conformer is A and which is B. Draw and Label the methyl group as axial or equatorial. G o Conformer A G o Conformer B [ G o equil = G o (products) - G o (reactants)] G o equil The equilibrium constant (Keq) for this interconversion is defined as: Keq = [products] [reactants] = [B] [A] Calculate the equilibrium constant for the conformer equilibrium using the equation shown below. Include the units and show your work. Keq %Conformer A %Conformer 14) Repeat this entire process for trans-1,4-di-methylcyclohexane and be certain that you record all of the steps, data, and calculations in your notebook. Once you have completed these two knowns as part of the tutorial, you will begin working on the last part which involves a di-substituted cyclohexane derivative given to each lab pair of students by your lab instructor. 15) First draw the structure in your notebook and record the IUPAC name for this molecule (ChemDraw can aide you) 16) Before you begin to draw too many structures on the computer, you should first draw the two chair conformers of your cyclohexane compound in your notebook and ask your lab instructor to verify your work with their initials. ** At this time you may continue working on this molecule in lab, or complete your work outside of lab. 17) Follow your earlier procedure to determine the total energy (G o ) for the two conformers, calculate G o equil, Keq, and the % of each conformer. Be certain that you have recorded all of the content, data, and calculations in your notebook. 18) Write a few sentences to explain your results from the methyl cyclohexane part of the experiment. Do they match your expectations? 19) Write a few sentences to explain your results from the trans-1,4-di-methyl cyclohexane part of the experiment. Do they match your expectations? 20) Write a few sentences to explain your results from the unknown di-substituted cyclohexane part of the experiment. Do they match your expectations?

5 Grading Rubric for Lab # 4 Section III - Background and Preparation (30 points max) - marked 1-6 What is cycloalkane ring strain? 5 What are cyclohexane chair conformers? 5 What is the difference between axial and equatorial positions on chair cyclohexanes? 5 How does one compare the stability of different chair conformers for a mono-substituted cyclohexane? 5 What do the terms cis and trans represent for di-substituted cyclohexane molecules? 5 What are 1,3-diaxial interactions? Why are they de-stabilizing to a conformer? 5 Pre-Lab Quiz (10 points max) - marked Pre-lab recitation notes, example problems, calculations, data, results (10 points max) marked 9-10 Fully detailed notes with all steps and calculations recorded 10 Moderately recorded notes with steps and calculations recorded 5-7 Poorly recorded notes 2-4 Section VI - work on methyl cyclohexane and trans-1,4-di-methylcyclohexane (20 points max) marked All data values and full calculations are recorded neatly in proper order 20 Moderately completed 15 Does not meet the requirements (little work shown) but data is still present 5 Section VI - work on last di-substituted cyclohexane (15 points max) marked All structures, data values, and full calculations are recorded neatly in proper order this includes drawn 15 structures, names, data, and calculations Moderately completed 10 Does not meet the requirements (little work shown) but data is still present 5 Discussion Questions (15 points max) marked Accurate description of expectations and results 15 Moderately addressed discussion 10 Does not meet the requirements 5