Chemoselectivity in Transfer-Hydrogenation Reactions: Experiment 36, Schemes and Mind Maps of Chemistry

Download Chemoselectivity in Transfer-Hydrogenation Reactions: Experiment 36 and more Schemes and Mind Maps Chemistry in PDF only on Docsity! 389 E X P E R I M E N T Chemoselectivity in Transfer-Hydrogenation Reactions 36 When chemists seek to develop new methods for synthesizing organic compounds, it is often important to fi nd reagents that react with only one functional group in a polyfunctional molecule. This type of reagent is said to be chemoselective. In the introduction for Experiment 13, the chemoselectivity of sodium borohydride was compared with that of lithium aluminum hydride. For ex- ample, sodium borohydride reduces aldehydes, ketones, and acid chlorides at 258C. Unlike lithium aluminum hydride, it has no effect on carboxylic acids, epoxides, nitro groups, nitriles, amides, or alkyl halides (Equations E36.1 and E36.2). O O OH NaBH4 OH Oworkup OH (E36.1) O O OH LiAlH4 OH workup OH (E36.2) Both of these reagents reduce polarized double bonds, but have no effect on carbon-carbon double bonds (Equations E36.3 and E36.4). OHO NaBH4 workup (E36.3) O LiAlH4 OH workup (E36.4) Hydrogen can be added across a carbon-carbon double bond in the presence of a suitable catalyst to give the corresponding alkane (Equa- tion E36.5). 29935_Exp_Ch30-36_p363-394 pp3.indd 389 11/25/09 2:21:06 PM 390 Part 2 ■ Experiments Figure E36.1 Substrates for the Transfer-Hydrogenation Reactions OCH2Ph O OH O F OH O Cl OMe ONO2 OH O NHAc O 1,3-diphenyl-2-propen-1-one methyl 2-nitrocinnamate4-fluorocinnamic acid benzyl cinnamate!-acetamidocinnamic acid 4-chlorocinnamic acid R1 R2 H H R1 R2 H H H H " H2 metal catalyst (E36.5) As discussed in the introduction to Experiment 17, the use of hydrogen gas and a metal catalyst presents safety hazards because of the fl ammabil- ity of hydrogen gas. In addition, specialized equipment is sometimes re- quired because of the high temperatures and pressures needed. Ammonium formate can be used as a hydrogen donor to hydrogenate a carbon-carbon double bond in the presence of a Pd/C catalyst (introduction to Experi- ment 17). Under these conditions, the carbon-carbon double bond of 3-phenylpropenoic acid is hydrogenated to leave the carboxylate group intact (Equation E36.6). OH O O NH4 O " CO2 Pd/C, HCO2 NH4 methanol, reflux (E36.6) In this experiment, the chemoselectivity of transfer-hydrogenation reac- tions using ammonium formate and palladium on carbon as a catalyst are examined using derivatives of 3-phenylpropenoic acid (cinnamic acid) and the structurally related ketone, trans-1,3-diphenyl-2-propen-1-one (chalcone) as substrates (Figure E36.1). Did you know? Finely divided palladium is able to adsorb up to 900 times its own volume of hydrogen. In the palladium on carbon catalyst, the palladium is distributed over finely divided carbon to increase the surface area and increase the activity of the catalyst. Because hydrogen diffuses through the catalyst when it is heated, palladium on carbon can be used to purify hydrogen. 29935_Exp_Ch30-36_p363-394 pp3.indd 390 11/25/09 2:21:08 PM Experiment 36 ■ Chemoselectivity in Transfer-Hydrogenation Reactions 393 If crystals are apparent after ten minutes• , allow the system to stand undis- turbed until no more crystals appear to be forming (approximately 10 min- utes). Isolate the crystals by fi ltering on a Hirsch funnel and wash them with cold 2-propanol. Dry the crystals and obtain a weight and a melting point. Dissolve some of the crystals in an appropriate solvent and spot the solution on a TLC plate. Compare the result obtained with the fi rst TLC plate that contained the starting material and the reaction mixture. If no crystals are apparent after ten minutes, • transfer the fi ltrate to a fi lter fl ask and remove the methanol by evaporation using a vacuum source that is equipped with a cold trap and heating gently. Do not overheat the solution. The product may be an oil that should not be mistaken for residual methanol. Add 4.5 mL of 1M HCl to the fl ask and 3 mL of ether. Swirl the con- tents of the fl ask until everything has dissolved. Transfer this mixture to a centrifuge tube, cover it, and shake to mix the contents well. After the layers separate, transfer the organic layer to a large test tube. Extract the aqueous layer with an additional 1.5 mL of ether and add the ether layer to the organic layer in the large test tube. Dry the combined organic layers with sodium sulfate (Section 7.7). Spot some of this solution on a TLC plate. Transfer the dried ether solution to a tared 10–mL beaker and evap- orate the ether in the fume hood using a stream of air. If you obtain a solid product after evaporation of the ether, take a melting point and dissolve some of the crystals in an appropriate solvent. Spot the solution on a TLC plate. Compare the result obtained with the fi rst TLC plate that contained the starting material and the reaction mixture. If you obtain an oil, compare the TLC result obtained from the dry ether solution with the fi rst TLC plate that contained the starting material and the reaction mixture. Cleanup Put the product in an appropriate container. Pour all organic solvents, including TLC solvents, and aqueous waste into the appropriate liquid waste containers. Put the pipettes used for fi ltering the palladium on carbon and the weigh paper used for the Pd/C in the specially labeled contain- ers of water found in the fume hood. Dispose of all contaminated Pasteur pipettes, used TLC plates, and melting point and TLC capillaries in the con- tainer for contaminated laboratory debris. Discussion for Laboratory Period 1: Analyze the • 1H and 13C[1H] NMR spectra of the substrate and the prod- uct. Assign the molecular ions in the EI mass spectra of the starting ma- terial and the product (Chapter 8). Your instructor will let you know how or where to obtain the spectra. SAFETY NOTE Palladium on carbon can be pyrophoric when exposed to air, especially when it is dry. Immediately after use, the Pasteur pipette containing the Pd/C should be submerged in the specially labeled container of water in the fume hood. 29935_Exp_Ch30-36_p363-394 pp3.indd 393 11/25/09 2:21:09 PM 394 Part 2 ■ Experiments Discuss how you used the spectral data to determine the structure of • your product. Write a balanced equation for the reaction.• Calculate the percent yield of the product.• Laboratory Period 2: Analysis of the Data from the Chemoselectivi ty in Transfer-Hydrogenation Reactions Experiment Your instructor will assign Alternative A or Alternative B. Alternative A You will collaborate with the other students who hydrogenated the same substrate. Each group of students who hydrogenated the same substrate should provide an oral presentation to the laboratory section that summa- rizes the results from the transfer-hydrogenation reaction of the assigned substrate. The presentation should include a balanced equation for the re- action and a discussion of the spectral data that supports your conclusion. For supporting evidence, it is sometimes important to consider the spectra of the starting material compared with the product. Each member of the group should present some aspect of the information. Presentations should include responses to questions from the audience. You should take notes on the results from the remaining fi ve substrates during the presentations in order to include them in your laboratory report. Alternative B During the laboratory period, your instructor will lead a discussion on the results obtained from the six substrates. Be prepared to answer questions about your experimental data and defend your conclusions. During the discussion, take notes about the data obtained for the other fi ve substrates in order to include all of the results in your laboratory report. Discussion for Laboratory Period 2: The purpose of this experiment is to evaluate the chemoselectivity of • transfer-hydrogenations using ammonium formate as the hydrogen donor. In the discussion, compare the functional groups present in all six substrates and their relative reactivities. Include balanced equations for the reactions for all substrates. In addition, discuss the results of the reactions shown in Equations E36.7 and E36.8. O O methanol, reflux Pd/C, HCO2 NH4 (E36.7) OMe O methanol, reflux Pd/C, HCO2 NH4 OMe O (E36.8) 29935_Exp_Ch30-36_p363-394 pp3.indd 394 11/25/09 2:21:10 PM