Homework answers / question archive / DETERMINATION DIASTEREOSELECTIVITY THERMODYNAMIC VERSUS CONTROLLED REDUCTIONS OF USING KINETIC A REDUCTION of 4-tert-BUTYLCYCLOHEXANONE REACTION: Oxidation of an Alcohol, Reductions of a Ketone 1 TECHNIQUES: TLC, Extraction, Extraction, H NMR spectroscopy In this multi-week experiment, we will explore the oxidation of a secondary alcohol to a ketone using an oxidizing reagent, sodium hypochlorite, which is a readily available reagent and a commonly used household cleaning product

DETERMINATION DIASTEREOSELECTIVITY THERMODYNAMIC VERSUS CONTROLLED REDUCTIONS OF USING KINETIC A REDUCTION of 4-tert-BUTYLCYCLOHEXANONE REACTION: Oxidation of an Alcohol, Reductions of a Ketone 1 TECHNIQUES: TLC, Extraction, Extraction, H NMR spectroscopy In this multi-week experiment, we will explore the oxidation of a secondary alcohol to a ketone using an oxidizing reagent, sodium hypochlorite, which is a readily available reagent and a commonly used household cleaning product

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DETERMINATION DIASTEREOSELECTIVITY THERMODYNAMIC VERSUS CONTROLLED REDUCTIONS OF USING KINETIC A REDUCTION of 4-tert-BUTYLCYCLOHEXANONE REACTION: Oxidation of an Alcohol, Reductions of a Ketone 1 TECHNIQUES: TLC, Extraction, Extraction, H NMR spectroscopy In this multi-week experiment, we will explore the oxidation of a secondary alcohol to a ketone using an oxidizing reagent, sodium hypochlorite, which is a readily available reagent and a commonly used household cleaning product. We will use TLC to monitor the progress of the oxidation reaction. Reduction of the ketone will be performed under different reaction conditions and the diastereoselectivity will be 1 determined by H NMR spectroscopy. READING ASSIGNMENT: Background handout This handout for procedure. Review online lecture videos! nd Review EXTRACTION in Making the connections (2 ed pg rd 128-140, 3 ed pg 130-142) See What is Extraction? See Extraction Overview See Uses for Extraction See Extraction Theory See Which layer is which? See Step By Step Procedures for Extraction See Acid-Base Extraction Review THIN LAYER CHROMATOGRAPHY in Making the nd rd connections (2 ed pg 162-172, 3 ed pg 164-174) See Overview of TLC See General Separation Theory See Step by Step Procedures for TLC See Visualizing Your TLC Plate See How to calculate Rf? nd Review IR SPECTROSCOPY in Making the connections (2 ed pg rd 65-76, 3 ed pg 65-76) See What is IR spectroscopy? See Theory of IR Spectroscopy See Identifying Particular Groups Via IR See IR: Interpretation See Interpreting IR Spectra nd Review NMR SPECTROSCOPY in Making the connections (2 ed rd pg 77-100, 3 ed pg 77-100) See Introduction to Proton NMR See Splitting–(n+1) Rule See Integration In Proton NMR and Integration in NMR nd Supplementary information in Janice Gorzynski Smith (2 ed), Chapter 12 IMPORTANT SAFETY INFORMATION 4-tert-butylcyclohexanol and 4-tert-butylcyclohexanone are irritants. Wear gloves and avoid all contact with skin, eyes, and clothing. 5.25% Sodium hypochlorite (NaOCl) is commercial bleach. The solution is colorless or slightly yellow with faint chlorine-like odor. Ingestion may cause corrosion of mucous membranes. Inhalation may produce severe bronchial irritation. Glacial Acetic Acid is an irritant and can cause severe burns. Use in the hood only! Wear gloves and avoid all contact with skin eyes, and clothing. Hydrochloric Acid is an irritant and can cause severe burns. Use in the hood only! Wear gloves and avoid all contact with skin eyes, and clothing. Sodium borohydride and aluminum isopropoxide are harmful and all contact with skin or eyes should be avoided! Sodium borohydride is also water reactive and may cause fires if exposed to it. Keep away from water unless specifically instructed! Diethyl ether is extremely volatile and flammable! Use it in the hood! Do not heat on hot plate. Hexanes are volatile, flammable, and a neurotoxin when inhaled. Use in fume hood only! Cover flask opening when transporting. Ethanol is volatile and flammable. It causes severe eye and respiratory tract irritation, and causes adverse reproductive and fetal effects in humans. Isopropanol is volatile and flammable. It causes severe eye and respiratory tract irritation, and causes adverse reproductive and fetal effects in humans. It can cause central nervous system depression, and inhalation can cause dizziness and drowsiness. Deuterated chloroform may be fatal if inhaled or swallowed. Possible carcinogen. Readily absorbed through the skin. Acts as a defatting agent in contact with skin. Harmful if splashed into the eye. Chronic exposure may cause liver and kidney damage. PRE-LAB ASSIGNMENT FOR PART 1: Complete all portions of pre-lab notebook work according to guidelines Draw a flow chart for the extraction procedure making note of which layer is which and where the desired compound is located Complete Video Quiz(zes) on Canvas Sapling assignment Complete your pre-lab certification on Canvas PART 1: OXIDATION OF 4-TERT-BUTYLCYCLOHEXANOL Experimental Procedure Dissolve 300 mg of 4-tert-butylcyclohexanol in 4 mL of acetone using a 25 mL round bottom-flask equipped with a magnetic stir bar on a magnetic stir-plate. Place a 100 mL beaker containing water (~50 mL) on a hot plate and heat to maintain the water o temperature at approximately 50 C (using a thermometer to measure this). Put the reaction flask into the warm water bath before adding 0.50 mL of glacial acetic acid, and start the oxidation by adding 4.0 mL of a 5.25% (0.75 M) sodium hypochlorite solution (commercial bleach). Stir the mixture vigorously with the help of a magnetic stir bar. Use TLC co-spotting technique to monitor the progress of the reaction every 10 minutes. Remove a small sample for TLC analysis (less than 1 drop using Pasteur pipette) from the organic layer if the reaction mixture separates into two layers. Which one is the organic layer? Once the conversion is complete and the reaction mixture shows no more starting material by TLC analysis, proceed with the workup of the 4-tert-butylcyclohexanol. A total of 5 mL of 5.25% NaOCl should be more than enough to convert all of the 4-tert-butylcyclohexanol to 4-tert-butylcyclohexanone. However, since NaOCl decomposes rapidly (eq 1), add an additional 0.5 mL of NaOCl solution if there is still starting material after 30 min. NaOCl + NaCl + H2O → Cl2 + 2 NaOH (eq 1) Checking Reaction Progress by TLC: The aliquot you removed for analysis might be very concentrated. If it appears that your sample is too concentrated for good TLC analysis, you can dilute the aliquot in a small flask or test tube using acetone as the solvent. Use 35% acetone/65% hexane, which you will need to make, as the TLC solvent. Since neither the starting material nor the product is UV active, visualization in this experiment will be accomplished using a KMnO4 stain. What makes a compound UV active? To stain your plate, submerge your TLC plate in the jar with the stain briefly (~1 sec). Allow the excess liquid to drain in the jar and then dab the bottom and back of the plate on a paper towel to remove any excess liquid. The plate will come out dark purple and after a few minutes bright yellow spots will appear. If you are not seeing spots you may place the plate into the oven for one minute. What data should you record? Work up: First, test the reaction mixture for excess hypochlorite by placing a drop of the reaction solution on a piece of wet starch-iodide indicator paper. The appearance of blue-black color from the formation of the triiodide-starch complex on the indicator paper signifies the presence of excess hypochlorite. If hypochlorite is present, add 0.5 mL of 2-propanol (isopropyl alcohol), stir the mixture, and again re-test the reaction mixture for the presence of any hypochlorite. If necessary, continue adding 2-propanol in 0.1 mL increments and testing with starch-iodide paper until excess oxidant is completely quenched. Why are we using isopropanol here? How does the addition of isopropanol lead to a lack of hypochlorite? Why are we not concerned about any additional products from this process? These should be mentioned briefly in your report! Transfer the reaction mixture into a 60-mL separatory funnel. Extract the reaction mixture two times, each with 10 mL hexane. Which layer contains your product – water or hexane? Wash the hexane extracts with 5 mL of 5% sodium bicarbonate solution, then wash with 5 mL of deionized water. What does the term “wash” mean? Dry the hexane extract with anhydrous sodium sulfate in a beaker for a few minutes. Tare a vial and transfer half of the hexane extract to it and begin evaporating the hexane using a gentle stream of air or by gently heating on a hot plate. As hexane evaporates, add the remaining extract to the vial and continue evaporating. Rinse the anhydrous sodium sulfate with 2 mL of hexane and add the rinsed hexane to the vial. What is the purpose of rinsing the drying agent? Finish evaporating the hexane to yield an off white or yellow colored residue of crude product. Cool the residue until it becomes a solid. Give your vial of product to your TA (making sure the vial is properly labeled). What is considered properly labeled? What data should you record? PRE-LAB ASSIGNMENT FOR PART 2: Complete all portions of pre-lab notebook work according to guidelines. You only need to include the information for the reduction reaction assigned to you. A hypothesis that addresses from which face each reducing agent will attack the carbonyl and why. Remember that anything is acceptable here as long as the rationale is reasonable. Draw a flow chart for the extraction procedure making note of which layer is which and where the desired compound is located Complete Video Quiz(zes) on Canvas Sapling assignment Complete your pre-lab certification on Canvas PART 2: REDUCTION OF 4-TERT-BUTYLCYCLOHEXANONE FOR DETERMINATION OF DIASTEREOSELECTIVITY AND THERMODYNAMIC VERSUS KINETIC CONTROL Your TA will assign one of the two reduction reactions to you for the second lab period. Procedure for Sodium Borohydride Reduction Remember to use an appropriate scale for the reduction reaction based on your yield from the previous week! You need 100 mg of 4-tert-butylcyclohexanone for this experiment, but if you don’t have enough left over the stockroom will provide you with extra. Dissolve 100 mg of 4-tert-butylcyclohexanone in 3 mL of ethanol in a 25 mL Erlenmeyer flask equipped with a magnetic stir bar on a magnetic stir plate. Slowly add the appropriate amount of sodium borohydride (3 molar equivalents) to the flask. Each 15 minutes, check the reaction progress using TLC (see instructions for monitoring the reaction progress as described previously under the “Checking Reaction Progress by TLC” section). Once you have determined the reaction is complete, slowly quench the reaction by adding 2 mL of deionized H2O dropwise, followed by dropwise addition of 3M HCl until no more H2 gas is evolved. Where does the gas come from? Cool the reaction mixture to room temperature and add 5 mL of Et2O. Transfer the solution into a separatory funnel. If there is solid in the bottom of the Erlenmeyer, carefully decant the solution into the separatory funnel leaving any solid behind. Rinse the remaining solids with 2 mL of diethyl ether and add it to the separatory funnel, again leaving the solid behind in the Erlenmeyer. Extract the reaction mixture and separate the layers and set the Et2O layer aside. Take the aqueous layer and extract with 5 mL of Et2O again. Add the ether layer from the second extraction with the one from the first extraction and pour it back into the separatory funnel. Wash the combined organic layers with 5 mL of deionized water. Dry the organic layer with anhydrous sodium sulfate for a few minutes. Transfer half of the organic layer to a tared vial and begin evaporating the ether using a gentle stream of air. As ether evaporates, add the remaining organic layer to the vial and continue evaporating. Rinse the anhydrous sodium sulfate with 2 mL of ether and add the rinsed ether to the vial. Evaporate the remaining ether in the vial in the fume hood by air stream. Cool the residue until it becomes a solid. What data should you record? Give your LABELED 4-tert-butylcyclohexanol product vial to your TA for NMR analysis. They will add ~0.50 mL deuterated chloroform to dissolve the solid. Consult with your TA if you have significantly less than 100 mg of product. Procedure for Meerwein-Pondorff-Verley Reduction In a 10-mL round bottom flask equipped with a stir bar and a condenser, combine 4.0 mL of isopropyl alcohol, 0.40 mL of acetone, 100 mg of 4-tert-butylcyclohexanone and 1.0 g of aluminum isopropoxide. Heat the solution to reflux for one hour. At this point, check the reaction progress using TLC (see instructions for monitoring the reaction progress as described previously under the “Checking Reaction Progress by TLC” section). Note that this reaction may not go to completion and that is ok (remember it is a reversible reaction!). After complete cooling, filter the reaction mixture to remove solids. Transfer the filtered reaction mixture to a separatory funnel. Add 20 mL water, then extract the mixture with two 10 mL portions of ether. Wash the combined ether layers with two 10 mL portions of H2O to remove most of the isopropyl alcohol that remains dissolved in the ether layer. Dry the combined ether layers over anhydrous MgSO4 and filter. Tare a vial and transfer half of the ether layer to it and begin evaporating it using a gentle stream of air. As ether evaporates, add the remaining ether layer to the vial and continue evaporating until you obtain a dry solid. What data should you record? Give your LABELED 4-tert-butylcyclohexanol product vial to your TA for NMR analysis. They will add ~0.50 mL deuterated chloroform to dissolve the solid. Consult with your TA if you have significantly less than 100 mg of product. Chem 51LC Experiment 4 Report Determination of Diastereoselectivity Using Thermodynamic Versus Kinetic Controlled Reductions: A Reduction of 4-tert-butylcyclohexanone Instructions Report scaffolds are provided to help you learn how to write about the experiments you conduct. In 51LB you finished the last lab by generating your own experiment-specific questions and answering them. Now you will begin to be responsible for writing a formal lab report in paragraph format. For this post-lab, you will need to write in paragraph format for the results, discussion, and conclusion sections. To assist you, the general questions to consider when writing a lab report that were provided to you in 51LB have been included below for those sections. For the introduction and theory sections, you will answer specific questions. Do not write the specific questions in your separate document. Do not include the general questions. Be sure to also write this lab report following the Lab Report Guidelines handout and use the rubric (located in the post-lab submission page) to ensure you are touching on all of the relevant points. Post-Lab Report Format: MUST BE TYPED IN WORD OR A SIMILAR PROGRAM, NOT AN ELN PAGE! Times New Roman; 12 pt. font; double spaced; 1” margins; no rd more than 5 pages; use 3 person passive voice only (For example, “We dissolved the white solid in 10 mL of hot water,” should be written as, “The white solid was dissolved in 10 mL of hot water.”). Include your name, student ID number, and lab course code. This format is NOT OPTIONAL. TAs will remove points for failure to follow instructions. Purpose/Introduction 1. What is the goal of this experiment and how is it being accomplished? You answer should address the reactions, the relevant reactants, the techniques being used, and the purpose of each technique. Why is the oxidation-reduction sequence being performed? Theory 2. How does the oxidation reaction work mechanistically? Explain the mechanism of the reaction in words. What is being reduced? What is being oxidized? What role does acetic acid play? 3. Why does nucleophilic attack occur at the chlorine atom? 4. Discuss the last step of the reaction. What similarity can you see between it and a previously-learned reaction. 5. Are the two faces of the ketone in the reduction reaction equivalent? Explain. 6. How does the choice of reducing agent affect which face is attacked? Which face will each reducing agent prefer? You should address all three reducing agents in your answer. This is your hypothesis from your pre-lab and does not need to be the “correct answer.” As long as your rationale is reasonable, even if your results do not support it, that is still worth full credit. 7. Draw the mechanism of the oxidation reaction and the mechanisms for all three reduction reactions. These may be attached in the appendix of the report. Results General Questions: What important data were obtained in this experiment? The data provided in this section should relate to the purpose(s) of the experiment, but you do not need to point out the connections here. Do not explain your results yet. Just provide them in an organized format. Don’t forget to include any assigned unknown number! You should include a table to organize your data. Include class data obtained from NMR spectra, as well as from the spectrum from the commercially-sourced starting material. For your individual reaction, include spectral data, yields, and TLC data. Include relevant calculations in the appendix. Discussion and Error Analysis General Questions: How do the data obtained relate to the purpose(s) of the experiment? How do you know the identity of the product and/or unknown? How efficient was the oxidation? How effective was the oxidation? Use data to support your argument. Do the results make sense? Are they consistent with your hypothesis? What conclusions can you draw from the data? What conclusions can you NOT draw from the data? How was the raw data processed? (Note that although you are provided with distinct, individual questions here, sometimes the answers to these questions might overlap with each other. That’s ok! In a lab report you would need to decide how to tie these answers together.) What is at least one problem you encountered or could have encountered in this experiment? If you determine that no errors occurred, analyze a potential error. What is your hypothesis to improve the problematic aspect of the experiment and how would you test your hypothesis with an analytical technique? What results from your test would support your hypothesis? Why is it important to resolve this error? You are not suggesting a fix to the error, only a way to prove that the error occurred and affected your results. Conclusions and Future Experiments General Questions: How would you summarize your results and analysis in 1-2 sentences? Was your objective met? In other words, what is it that you want the reader to remember after having read your paper? What questions remain unanswered? What questions were raised by your results and analysis? What experiment would you perform if you wanted to further probe this reaction? Oxidation-­Reduction  Spectra     IR  Spectra     Starting  Material:  4-­?tert-­?  butylcyclohexanol   Oxidized starting material: 4-­?tert-­?  butylcyclohexanone NMR  Spectra Starting  Material:  4-­?tert-­?  butylcyclohexanol   Courtesy of: http://www.chem.wisc.edu/courses/342/Fall2006/Experiment_8.pdf Reduction  of  4-­?tert-­?  butylcyclohexanone  to 4-­?tert-­?  butylcyclohexanol using three different procedures. The NMR spectra are labeled with the appropriate reductions. Courtesy of: Novak, M.; Gung, B. W.; Hershberger, J. W.; Taylor, R. T.; Emenike, B.; Chakraborty, M.; Scioneaux, A. N.; Ponsot, A. E.; Daka, P. Chem. Educator 2009, 14, 232–235. http://chemeducator.org/sbibs/s0014006/spapers/14090232mn.pdf   Group Oxidation Yield (g) Reduction Name (Borohydride or MPV) Reduction Yield (g) Number of Spots on TLC of Reduction Product Rf(s) of TLC Spots from Reduction Product 1 0.218 Borohydride 0.087 1 0.56 2 0.093 Borohydride 0.264 1 0.40 3 0.216 Borohydride 0.100 1 0.47 4 0.338 MPV 0.082 1 0.76 5 0.311 MPV 0.063 1 0.71 6 0.137 MPV 0.005 1 0.78 7 0.224 MPV 0.004 1 0.64 MPV NaBH4 Reduction Name Reduction Yield MPV 0.090 g Percent Yield Number of Spots on TLC of Reduction Product Rf(s) of TLC Spots from Reduction Product 89% 2 0.568, 0.682 4:04 ull LTE Done 51LC - Oxidatio... Oxidation TLC Data Mass (g) 4-tert-butylcyclohexanol 0.305 Vial 16.236 Vial + Product 16.604 Distance (cm) Solvent Front 4.5 Starting Material (Left Lane) 1.7 Reaction Mixture (Right Lane) 2.0