Oxidation-Reduction Scheme PDF

Page < II ) of 114 AN OXIDATION-REDUCTION SCHEME REFERENCES Pavia et al (4/e): Tech. 6.3, 12.3-12.6, 12.9-12.10, 8.3 Klein (1/e): Section20.3; Section20.9; and Sections 13.4, '13.10 This experiment will be divided into two parts...

Page < II ) of 114 AN OXIDATION-REDUCTION SCHEME REFERENCES Pavia et al (4/e): Tech. 6.3, 12.3-12.6, 12.9-12.10, 8.3 Klein (1/e): Section20.3; Section20.9; and Sections 13.4, '13.10 This experiment will be divided into two parts: 6A and 6B. There will be separate pre-labs for each part, but only one lab quiz covering the information and procedures for both parts. The final post-laboratory write-up should include both parts together. EXP. 6A- OXIDATION OF BORNEOL TO CAMPHOR Secondary alcohols such as bomeol are commonly oxidized to ketones (in this case camphor) using a solution of sodium dichromate or chromium trixoide in sulfuric acid. Na2Cr20 7 ( or Cr03) H H2S04 OH ~' However, the chromate solutions involved (bo~ cr3+ and Cr61 are carcinogenic and caustic. To avoid the haz.ard and expense involved in this procedure, we will be using a less common but safer hypochlorous acid oxidation. The hypochlorous acid will be generated by treating common household bleach (sodium hypochlorite) with acetic acid. NaOCI H CH3COOH OH (HOCI) We have had problems in the past with the reaction not going to completion. We thus obtain a camphor product contaminated with a significant amount ·of unoxidized bomeol. To ensure that complete oxidation of the alcohol occurs, it is necessary to employ a large excess of sodium hypochlorite. EXP. 68 - REDUCTION OF CAMPHOR Sodium borohydride (NaBH4) will be used to reduce the camphor product from p~ A to isobomeol. Sodium borohydride is used rather than lithium aluminum hydride because it is easier to handle and can be used in protic solvents. In this reaction, the reduction is stereospecific with the hydride approaching camphor from the bottom side (endo approach) due to steric repulsion of  ~.--.. Page ( ) of114 I the two methyl groups on the bridge of the top side. Thus, the major product obtained will be isobomeol with a small amount of bomeol perhaps being seen. The exact percentage of each isomer can be determined by NMR H3C CH3 "~ borneol H3C CH3 ~ £.}--fH vkHe OH q;}{ (exo - minor) ~ 3 ~en H3\L (endo - major) £.}--fOH isoborneol H PROCEDURE - PART A To a 50-mL round bottom flas~ add 0.360 g of racemic bomeol, 1.0 mL of acetone, and 1.0 mL of glacial acetic acid. Place a magnetic stirbar in the flask as well. Prepare a warm water bath (50 °C) as shown in Technique 6.3. Clamp the round-bottom flask J'J that the warm water covers the bottom 2/3 of the flask. Stir the mixture until the bomeol dissolves. Add 0.5 mL of acetone if it does not dissolve after several minutes of stirring. Measure out 20 mL of 10--14% sodium hypochlorite solution. Add 2 mL of this solution dropwise every 4 minutes to the bomeol mixture. The entire addition will take about 40 minutes. Heat and stir the mixture the entire time. When the reaction is complete, remove it from the warm-water bath and allow it to cool to room temperature. Transfer the mixture to a separatory funnel and then add 5.0 mL of m~thyene chloride to the round-bottom flask. Swirl to dissolve any product remaining on the walls of the flask. Transfer this methylene chloride rinse solution to the separatory funnel containing the reaction mixture. Stopper the separatory funnel and shake gently in order to avoid an emulsion. Remove the organic layer and place it in a clean beaker. Repeat the extraction with a second 5.0 mL portion of methylene chloride and add this to the first methylene chloride solution. Wash the combined methylene chloride layers with 3..0 mL of saturated sodium bicarbonate solution. Shake gently until you do not see any more CO2 evolving. Transfer the lower methylene chloride layer back to the separatory funnel and wash it with 3.0 mL of 5% aqueous sodium bisulfite. Remove the lower organic layer and transfer back to the separatory funnel and wash it with 3.0 mL of water. Finally, transfer the organic layer to a clean, dry beaker and diy it with anhydrous sodium sulfate. Decant the dried solution into a clean, dry, pre-weighed 20--mL beaker and place in fume hood to evaporate the solvent until next lab period.  - Page ( Ill > of 114 ALTERNATE PROCEDURE-PART A Dissolve 1.0 g ofbomeol in 4 mL of ethyl acetate in a 50 mL round-bottomed flask. While soluti~n is stirred, add 0.6 molar equivalents of Oxone and 0.2 molar equivalents of sodium chloride followed by 1.5 mL of water. Stir the reaction vigorously for 50 minutes at room temperature. Add 0.5 mmol of additional NaCl and stir for an additional 10 minutes. Add 15 mL of water to dissolve the salts and then extract 2 times with ethyl acetate, dry over sodium sulfate and evaporate. After you have isolated the camphor and allowed it to dry, obtain the mass of the sample and calculate the percent yield. If you leave the sample in your loc~er, store it in a tightly stoppered vial. ' We will verify that the oxidation was successful by taking an IR spectrum of the sample and detennining its melting point before continuing to part B. Your 'instructor may also have you verify the product using GC/MS analysis. PROCEDURE - PART B For the second part of this experiment, you will use your entire sample from part A (assuming that your melting point and IR spectrum verified that you indeed made camphor and it is not contaminated!), scaling up other reagents as necessary. You shoj:Jd reduce a sample of camphor that has a mass of at least 0.2 g-add some stock camphor to }~ur sample if necessary. Add at least 0.2 g of camphor to a small Erlenmeyer flask. Add 4.0 mL of methanol to the flask. Stir with a glass stirring rod until the camphor dissolves. Add 0.4 g of sodium borohydride to the solution. This is a large excess, but past experience shows that it gives the best results. Warm the contents of the flask on a warm hot plate (low setting) for 2 minutes. If the mixture begins to dry out, add more methanol as necessary. Don't let it run dry; the reaction will not work weU if the reagents are not in solution! Allow the mixture to cool and slowly add 5.0 mL of ice-cold water. Collect the white solid using vacuum filtration~ Allow the solid to dry under suction for several minutes, then transfer the solid to a small Erlenmeyer flask. Dissolve the solid in approximately 5 mL of methylene chloride. If you notice that a lot of product has remained in the original reaction, flask, add 1 mL of methylene chloride to the flask, swirl to dissolve any residual product, and add this to the methylene chloride solution containing the majority of the product. Dry the methylene chloride solution using anhydrous sodium sulfate for 15 minutes. Decant the dried solution into a clean, dry, pre-weighed vial and gently evaporate the solvent in the hood. Allow your sample to dry and determine the product mass and calculate the percent yield. We will verify that the reduction was successful by melting point, IR, and NMR analyses. In order to obtain a decent NMR_ spectrum without an excessively noisy baseline, you will need to dissolve your entire sample in CDCh/fMS. Place the sample in a small container, add a small amount of the NMR solvent, and dissolve· the sample. Using a pipet, transfer the solution to ------ ---- - - - - - - - - -- - - - - - - - - - --- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 4 an NMR tube, adding more solvent as necessary to get the solution to the correct height in the NMR tube. When you are finished, you can recover the isobomeol for further tests by simply transferring the solution from the NMR tube into a small conical vial and gently evaporating the solvent from the sample.. The NMR will be used to determine which isomer you made: isobo meol or bomeol. You will focus on the region around 3.5-4 ppm (which hydrogen "!respons ible for this signal?). In order to identify which peak belongs to which isomer, consult the NMR spectra for the two isomers given at the end of this lab. If the NMR spectrum shows that you obtained a mixture of both isomers, you will need to integrate the two peaks so that you can deter mine the relative·percent isobomeol:bomeol obtained. At the instructor's discretion, you may be directed to run a tic of your product vs. samples of camphor, bomeol, and isobomeol using methylene chloride as the solvent. This will tell you if you have any starting material (camphor) remaining and which isome r predominates.