Experiment 43: Effect of Reaction Conditions on the Condensation of Furfural with Cyclopentanone (from Lehman text, 2nd edition) Goals: • To synthesize and purify Product B

Experiment 43: Effect of Reaction Conditions on the Condensation of Furfural with Cyclopentanone (from Lehman text, 2nd edition) Goals: • To synthesize and purify Product B. • To determine Product A and Product B in the following reaction by looking closely at the reaction conditions in procedure A and procedure B, and by analyzing the NMR spectra for each of the products. The Reaction: O O O OH A or B H * Read the entire lab experiment in the Lehman text (pages 370 – 378) to obtain a more complete understanding of Experiment 43 (Note: The full experiment is provided on Canvas). Procedure Notes: *Note: We will performing the procedure for Part B only using the Standard Scale procedure (You can ignore the microscale procedure). These are only supplementary notes below. Please see the full procedure on page 377 of the experiment. Reaction: • Combine cyclopentanone, diethyl ether, NaOH, phase-transfer catalyst and stir bar in a 125 mL Erlenmeyer flask (Note that you will need to calculate the mass of cyclopentanone needed). • Cool the mixture in an ice/water bath before adding furfural. • Seal the flask with parafilm and stir vigorously on stir plate for 15 minutes. Occasionally swirl your reaction flask in the ice/water bath to reduce pressure build-up. • Continue mild stirring of the reaction mixture at room temperature for an additional 10 minutes. Separation: • Collect the product by vacuum filtration, rinsing the flask and washing the crystals with two small portions of diethyl ether. • Let the crude product air-dry on the filter under vacuum for a few minutes. Purification and Analysis: • Transfer the crude product into a pre-weighed 125 mL Erlenmeyer flask for recrystallization. Obtain the mass of the crude product. • Recrystallize the crude product with the minimum amount of 2-butanone (approximately 12 mL per gram of crude product). • • • Collect the product by vacuum filtration, rinsing and washing with a couple small portions of ether. Let the crystals air-dry on the filter under vacuum for a few minutes. Obtain the melting point range of the product. NMR spectra of products A and B are provided on Canvas. Lab Report Instructions: 1. Title Page 2. Analysis: • Draw the structures of Product A and Product B • Calculate the theoretical yield and % yield of Product B (Show calcs). • Provide the melting point range for Product B. • Draw structures of Product A and Product B in which all of the hydrogens are labeled as either Ha, Hb, Hc, etc, corresponding to the labeled peaks on the given NMR spectrum for each product. • Provide answers to Exercises 1, 3 and 5d in the Lehman text. *Note: Your report should be uploaded to Canvas in pdf or Microsoft Word format. M44_LEHM3752_02_SE_C43.QXD 2/25/08 3:58 PM Page 370 370 Part II EXPERIMENT Effect of Reaction Conditions on the Condensation of Furfural with Cyclopentanone 43 Correlated Laboratory Experiments Reactions of Carbonyl Compounds. Preparation of a, b -Unsaturated Carbonyl Compounds. Nucleophilic Addition. Condensation Reactions. Carbanions. NMR Spectrometry. Operations OP-8 OP-10 OP-16 OP-17 OP-18 OP-19 OP-24 OP-25 OP-26 OP-28 OP-31 OP-33 OP-40 Cooling Mixing Vacuum Filtration Centrifugation (µS) Extraction Evaporation Washing Liquids Drying Liquids Washing and Drying Solids Recrystallization Vacuum Distillation Melting Point Nuclear Magnetic Resonance Spectrometry Before You Begin 1. Read the experiment, read or review the operations as necessary, and write an experimental plan. Read OP-31 carefully if you haven’t performed a vacuum distillation before. 2. For part A, calculate the mass and volume of 50.0 mmol (SS) or 10.0 mmol (µS) of cyclopentanone and of 50.0 mmol (SS) or 10.0 mmol (µS) of furfural. 3. For part B, calculate the mass and volume of 10.0 mmol (SS) or 2.50 mmol (µS) of cyclopentanone. Scenario Grits ’n Groats, a breakfast-cereal manufacturer, produces huge quantities of oat hulls and corncobs while processing cereal grains. In the past, the company has simply disposed of such by-products, but the rising cost of waste disposal has convinced the board of directors that Grits ’n Groats should find a way to profit from them rather than paying to get rid of them. Oat hulls, corncobs, and other agricultural by-products can be processed to yield furfural, an aldehyde with an aromatic furan ring. While searching the chemical literature for references to furfural, project leader Farina Millet came across a paper in the Journal of Organic Chemistry that described a Claisen–Schmidt reaction (a type of aldol condensation) between cyclopentanone and furfural. Under one set of conditions, the reaction M44_LEHM3752_02_SE_C43.QXD Experiment 43 2/25/08 3:58 PM Page 371 Effect of Reaction Conditions on the Condensation of Furfural with Cyclopentanone yields a low-melting yellow solid; but, under a different set of conditions, it produces a high-melting golden-orange solid. Dr. Millet needs some samples of these compounds and their structures so that she can explore their potential for commercial development. Your assignment is to synthesize both compounds and to identify them using your chemical intuition, with some help from NMR spectrometry. 371 Key Concept: Different products can sometimes be produced from the same set of reactants by varying the reaction conditions. Applying Scientific Methodology After reading the experiment and comparing the reaction conditions, you should be able to formulate a tentative hypothesis about the structures of the products and predict the kind of 1H NMR spectrum each product should have. You will test your hypothesis when you obtain the actual NMR spectra of the products. From Oats to Furfural Furfural, also known as 2-furaldehyde, is the most important member of the furan series of aromatic compounds. The furan ring is aromatic because it has six pi electrons (two from the oxygen atom) distributed about a fivemembered ring (see Figure 43.1). The aromatic sextet of a furan ring is less stable than that of a benzene ring, so furans undergo such reactions as electrophilic addition, cycloaddition, and cleavage more readily than the corresponding benzene compounds. Furfural can be prepared in large quantities by treating such agricultural by-products as bran, oat hulls, corncobs, and peanut shells with dilute acids. These materials contain polysaccharides known as pentosans that are hydrolyzed to pentoses (simple five-carbon sugars) under acidic conditions. The pentoses are then converted to furfural by acid-catalyzed dehydration. Conversion of a pentose to furfural. (This equation represents the overall process, not the reaction mechanism.) HO OH H H H H OH HO a pentose H –3H2O CHO CHO O furfural O Figure 43.1 Aromatic furan ring O C O furfural H M44_LEHM3752_02_SE_C43.QXD 2/25/08 3:58 PM 372 Page 372 Part II O CH O CHC OH furylacrylic acid Correlated Laboratory Experiments The first commercial process for the manufacture of furfural was developed in 1922 by the Quaker Oats Company, which was trying to convert oat hulls into better cattle feed at the time. Instead, it came up with a valuable commercial product that can be made cheaply on a large scale. Furfural is used in the purification of lubricating oils, the extractive distillation of 1,3butadiene (used in the manufacture of rubber), the synthesis of phenolic resins, and the manufacture of a large number of chemical intermediates. Furfural behaves like a typical aromatic aldehyde in many of its reactions. It can be oxidized to the corresponding carboxylic acid and reduced to the corresponding alcohol, and, like benzaldehyde, it undergoes the Cannizzaro reaction and the benzoin condensation. It also reacts with compounds that have active a-hydrogen atoms, such as aldehydes and ketones, to yield condensation products. For example, the reaction of furfural with acetone yields furfurylideneacetone by a Claisen–Schmidt reaction, and its condensation with acetic anhydride and sodium acetate forms furylacrylic acid by a Perkin reaction. Claisen–Schmidt reaction of furfural and acetone O CHO O + CH3CCH3 O OH– CH CHCCH3 O furfurylideneacetone Understanding the Experiment Mechanism of a Claisen–Schmidt condensation O CH3CCH3 O – OH– CH2CCH3 O– PhCH PhCHO O CH2CCH3 OH H 2O O PhCHCH2CCH3 OH OH– O – PhCHCHCCH3 –OH– O PhCH CHCCH3 A Greener Way: You can recover the diethyl ether by evaporating it under vacuum using a cold trap. The Claisen–Schmidt reaction is a kind of crossed aldol condensation between an aromatic aldehyde and an aliphatic aldehyde or ketone that yields an a, b -unsaturated aldehyde or ketone. As illustrated in the margin for the reaction of benzaldehyde and acetone, the aliphatic carbonyl compound loses a proton to form an enolate ion, which attacks the carbonyl carbon of the aromatic aldehyde to yield (after protonation) a b -hydroxy carbonyl compound. This intermediate is generally not isolated but undergoes basecatalyzed dehydration by an E1cb mechanism. The base removes a proton from the a-carbon to form another enolate ion, which loses an OH- ion to yield the unsaturated product. In one of the procedures referred to in the Scenario, equimolar amounts of cyclopentanone and furfural are dissolved in diethyl ether and stirred with an aqueous solution of dilute sodium hydroxide. Furfural tends to oxidize and turn dark brown in storage, so furfural from a previously opened bottle should be distilled before use. Because the organic reactants are not very soluble in water, they tend to stay in the ether phase, necessitating vigorous stirring to mix the layers. Extraction of the reaction mixture with diethyl ether followed by evaporation of the ether yields an impure yellow liquid, which is distilled under vacuum to produce a liquid product that should crystallize to a low-melting yellow solid, product A. Although the product usually doesn’t solidify until the distillate is cooled, the standard scale vacuum distillation should be monitored closely to make sure that a solid doesn’t form in the vacuum adapter and plug it up. Product A can be purified further by mixed-solvent recrystallization from methanol and water. M44_LEHM3752_02_SE_C43.QXD Experiment 43 2/25/08 3:58 PM Page 373 Effect of Reaction Conditions on the Condensation of Furfural with Cyclopentanone When cyclopentanone in diethyl ether is stirred with excess furfural in the presence of an effective phase-transfer catalyst such as tricaprylmethylammonium chloride (Aliquat 336), golden-orange crystals of product B begin to crystallize from the reaction mixture almost immediately. The exothermic reaction generates enough heat to vaporize the ether, making it necessary to cool the reactants in an ice/water bath before and during the reaction period. Product B is separated by filtration and purified by recrystallization from 2-butanone. The role played by the phase-transfer catalyst in aldol-type condensations is not entirely clear, but the catalyst may carry hydroxide ions into the organic phase where they can generate enolate ions, which then react with furfural molecules. (See Experiment 24 for information about phase-transfer catalysis.) From the structures of the reactants and your knowledge of aldoltype condensation reactions, you should be able to propose likely structures for the two products. The 1H NMR spectra will show clearly which product you have actually prepared in each case. In interpreting the spectra, you should pay particular attention to the number and multiplicity of signals produced by the methylene protons of the cyclopentanone ring. Comparing your spectra with the 1H NMR spectra of the reactants in Figure 43.2 should help you assign the signals in your spectra to specific proton sets. Although the stereochemistry of the products has not been reported in the literature, most reactions of this type yield the (E) isomers, as in the condensation of benzaldehyde with 4,4-dimethyl-1-tetralone. + PhCHO KOH C O O 4,4-dimethyl1-tetralone Ph H (E)-2-benzal-4,4-dimethyl1-tetralone The nearby carbonyl group has a deshielding effect on the vinylic proton of the (E) isomer, raising its chemical shift to 7.7 ppm, compared to a value of 6.6 ppm for the (Z) isomer. Furfural may be harmful to the environment, especially with regard to aquatic organisms. Diethyl ether is not considered toxic to aquatic life and does not persist for long in either air or water. Deuterochloroform is toxic to aquatic organisms and should not be released into the environment. 2-Butanone is not expected to be toxic to aquatic life or to significantly bioaccumulate. Reactions and Properties + CHO O OH– –H2O A or B O cyclopentanone furfural (equation not balanced) 373 A Greener Way: The part B reaction can be run without solvent by weighing the cyclopentanone into a 13 * 100-mm test tube, adding 0.01 g of finely divided potassium hydroxide, and then adding the furfural to the cooled mixture—with continuous stirring—until the mixture solidifies. After about 15 minutes, the solid is broken up by stirring with 2 mL 95% ethanol, and enough 3 M HCl is added to neutralize the KOH. The solid is then collected by vacuum filtration, washed with cold 95% ethanol, and recrystallized as directed. M44_LEHM3752_02_SE_C43.QXD 374 2/25/08 3:58 PM Page 374 Part II Correlated Laboratory Experiments Table 43.1 Physical properties furfural cyclopentanone 2-butanone tricaprylmethylammonium chloride product A product B mol wt mp bp 96.1 84.1 72.1 404.2 162.2 240.3 - 39 - 51 - 86 162 131 80 60.5 162 15415 Note: mp and bp are in °C; superscripts indicate pressure in torr; density is in g/mL. Cyclopentanone 2-Furaldehyde (furfural) Figure 43.2 NMR spectra of the starting materials d 1.159 0.949 0.805 0.884 M44_LEHM3752_02_SE_C43.QXD Experiment 43 2/25/08 3:58 PM Page 375 Effect of Reaction Conditions on the Condensation of Furfural with Cyclopentanone 375 DIRECTIONS A. Claisen–Schmidt Reaction of Cyclopentanone and Furfural Cyclopentanone is a skin irritant and a severe eye irritant; avoid contact. Diethyl ether is extremely flammable and may be harmful if inhaled. Do not breathe its vapors, and keep it away from flames and hot surfaces. Furfural irritates the skin, eyes, and respiratory tract, and it may cause allergic skin or respiratory reactions. Wear gloves while handling furfural and the reaction mixture (which will stain your hands yellow), and do not breathe their vapors. A vacuum-distillation apparatus may implode if any of its components are cracked or otherwise damaged. Inspect the parts for damage, and have your instructor check your apparatus. Protect yourself with a safety shield or hood sash while the apparatus is under vacuum. Deuterochloroform is harmful if inhaled or absorbed through the skin, and it is a suspected human carcinogen. Avoid contact with the liquid, and do not breathe its vapors. Safety Notes 2 1 3 1 2 0 cyclopentanone furfural 4 0 1 3 diethyl ether Standard Scale Reaction. In a 125-mL Erlenmeyer flask, dissolve 50.0 mmol of cyclopentanone in 25 mL of solvent-grade diethyl ether. Add 45 mL of 0.10 M aqueous sodium hydroxide and a magnetic stir bar. Cool [OP-8] the mixture to 5°C in an ice/water bath, and add 50.0 mmol of freshly distilled furfural while stirring. Seal the flask with Parafilm, and stir [OP-10] the reaction mixture vigorously in a cold water bath (10–15°C) for 45 minutes. Parafilm dissolves in ether, so don’t let it contact the reaction mixture. Replace any ether that evaporates during the reaction. Separation. Using a clean filter flask, filter the reaction mixture by vacuum filtration [OP-16] and save the filtrate, which contains product A. Turn off the vacuum immediately after filtration to keep the ether from evaporating. Wash any solid on the filter with 10 mL of diethyl ether, and combine the wash liquid with the filtrate. If your instructor assigned Exercise 2, save this solid and weigh it when it is dry. If any solid remains in the filtrate, it will be removed during subsequent operations. Place the filtrate in a separatory funnel and separate the layers, saving both layers. Extract [OP-18] the aqueous layer with 15 mL of ethyl ether, and combine the ether extract with the initial ether layer. Wash [OP-24] this solution with two separate portions of saturated aqueous sodium chloride. Dry [OP-25] it over anhydrous sodium sulfate or magnesium sulfate, and evaporate [OP-19] the ether under vacuum until the volume of the liquid residue remains essentially constant. Purification and Analysis. Assemble an apparatus for vacuum distillation [OP-31], using the compact apparatus shown in Figure E9 of OP-27, and have your instructor approve it. Make sure that a safety shield or hood sash is between you and the apparatus, and then purify the residue by vacuum distillation using no cooling bath. Monitor the distillation carefully; if any solid begins to form in the outlet tube, melt it with a heat gun or Take Care! Keep diethyl ether away from ignition sources, and do not breathe its vapors. Wear gloves, avoid contact with furfural, and do not breathe its vapors. Observe and Note: What happens during the reaction period? Stop and Think: What could this solid be? Waste Disposal: Place any recovered ether in a solvent recovery container. Unless your instructor directs otherwise, wash all aqueous layers down the drain. Take Care! A vacuum-distillation apparatus may implode if any of its components are cracked or otherwise damaged. Follow the precautions described in OP-31 and the Safety Notes. M44_LEHM3752_02_SE_C43.QXD 2/25/08 3:58 PM 376 Stop and Think: At about what temperature should the product distill? Waste Disposal: Place any lowboiling forerun in an appropriate waste container. Take Care! Avoid contact with CDCl3, and do not breathe its vapors. Page 376 Part II Correlated Laboratory Experiments another appropriate heating device. Any unreacted starting materials and residual ether should distill below 100°C and should be removed before the main fraction begins to distill. While the distillate is still liquid (warm it gently, if necessary), transfer it to a container suitable for recrystallization and cool it in ice water, if necessary, until it completely solidifies. Purify the solid by mixed-solvent recrystallization [OP-28b] from methanol and water, taking measures to prevent oiling. Dry [OP-26b] it at room temperature. Measure the mass and melting point [OP-33] of product A. Record its 1H NMR spectrum [OP-40] in deuterochloroform, or obtain a spectrum from your instructor. Interpret the NMR spectrum as completely as you can, deduce the structure of product A, and name it. Microscale Take Care! Keep diethyl ether away from ignition sources, and do not breathe its vapors. Wear gloves, avoid contact with furfural, and do not breathe its vapors. Observe and Note: What happens during the reaction period? Stop and Think: What could this solid be? Waste Disposal: Place any recovered ether in a solvent recovery container. Unless your instructor directs otherwise, wash all aqueous layers down the drain. Take Care! A vacuum-distillation apparatus may implode if any of its components are cracked or otherwise damaged. Follow the precautions described in OP-31 and the Safety Notes. Stop and Think: At about what temperature should the product distill? Reaction. In a 25-mL Erlenmeyer flask, dissolve 10.0 mmol of cyclopentanone in 6.0 mL of solvent-grade diethyl ether. Add 9.0 mL of 0.10 M aqueous sodium hydroxide and a stir bar. Cool [OP-8] the mixture to 5°C in an ice/water bath, and add 10.0 mmol of freshly distilled furfural while stirring. Seal the flask with Parafilm, and stir [OP-10] the reaction mixture vigorously in a cold water bath (10–15°C) for 45 minutes. Parafilm dissolves in ether, so don’t let it contact the reaction mixture. Replace any ether that evaporates during the reaction. Separation. Obtain and label three 15-mL centrifuge tubes. Cool a clean filter flask in an ice/water bath, and then filter the reaction mixture by vacuum filtration [OP-16]. Save the filtrate, which contains product A. Turn off the vacuum immediately after filtration to keep the ether from evaporating. Wash any solid on the filter with 2 mL of diethyl ether, and combine the wash liquid with the filtrate. If your instructor assigned Exercise 2, save this solid and weigh it when it is dry. If any solid remains in the filtrate, it will be removed during subsequent operations. Transfer all of the filtrate to the first two centrifuge tubes, alternating from one to the other, so that both contain about the same volume of each layer. Use a small amount of diethyl ether for the transfer. Centrifuge [OP-17] the contents of both tubes until the layers are cleanly separated. If necessary, add enough additional ether to provide a 2-cm layer of ether in each centrifuge tube, and shake gently to mix the layers thoroughly. Transfer both aqueous (lower) layers to the third centrifuge tube. Extract [OP-18] this aqueous solution with 3 mL of diethyl ether, remove the aqueous layer, and combine all of the ether layers in one centrifuge tube. Wash [OP-24] the ether solution with two separate 2-mL portions of saturated aqueous sodium chloride. Dry [OP-25] it with anhydrous sodium sulfate, and evaporate [OP-19] the ether (in portions, if necessary) until the volume of the liquid residue remains essentially constant. Purification and Analysis. Assemble an apparatus for vacuum distillation [OP-31] using a Hickman still and a 10-mL round-bottom flask, and have your instructor approve it. Make sure that a safety shield or hood sash is between you and the apparatus, and then purify the residue by vacuum distillation. Any residual ether and unreacted starting materials should distill below 100°C and should be removed before the main fraction begins to distill. Before allowing the Hickman still to cool, transfer the liquid M44_LEHM3752_02_SE_C43.QXD Experiment 43 2/25/08 3:58 PM Page 377 Effect of Reaction Conditions on the Condensation of Furfural with Cyclopentanone distillate (the main fraction) to a tared vial or another suitable container; cool it in ice water, if necessary, until it completely solidifies. (At your instructor’s request, you can purify the product further by mixed-solvent recrystallization [OP-28b] from methanol and water.) Dry [OP-26b] it at room temperature. Measure the mass and melting point [OP-33] of product A. Record its 1H NMR spectrum [OP-40] in deuterochloroform, or obtain a spectrum from your instructor. Interpret the NMR spectrum as completely as you can, deduce the structure of product A, and name it. 377 Waste Disposal: Place any lowboiling forerun in an appropriate waste container. Take Care! Avoid contact with CDCl3, and do not breathe its vapors. B. Claisen–Schmidt Reaction Using a Phase-Transfer Catalyst 2-Butanone is flammable, and ingestion, inhalation, or skin absorption may be harmful. Avoid contact, do not breathe its vapors, and keep it away from flames and hot surfaces. See part A for safety notes about cyclopentanone, diethyl ether, furfural, and deuterochloroform. Safety Notes 3 1 0 3 2-butanone Standard Scale Reaction. Weigh 10.0 mmol of cyclopentanone into a 125-mL Erlenmeyer flask, and dissolve it in 10 mL of diethyl ether. Add 12 mL of aqueous 0.10 M sodium hydroxide, 6 drops of tricaprylmethylammonium chloride (or 0.2 g of a suitable solid phase-transfer catalyst), and a stir bar. Cool [OP-8] the mixture to 5°C in an ice/water bath, and add 2.0 mL of freshly distilled furfural with stirring [OP-10]. Seal the flask with Parafilm, and stir it vigorously at room temperature for 15 minutes, occasionally swirling it in the ice/water bath to reduce pressure buildup from vaporizing ether. (Parafilm dissolves in ether, so don’t let it contact the reaction mixture.) Then let the reaction mixture stand at room temperature, with stirring or occasional shaking, for 10 minutes. Separation. Collect the product by vacuum filtration [OP-16], wash it with two portions of diethyl ether, and air-dry it on the filter. Purification and Analysis. Recrystallize [OP-28] product B from 2-butanone, using about 12 mL of the solvent per gram of crude product. Wash the product on the filter [OP-26a] with diethyl ether, dry it [OP-26b], and weigh it. (Waste Disposal: Place the filtrate in a designated solvent recovery container.) Measure the melting point [OP-33] of product B. Record its 1H NMR spectrum [OP-40] in deuterochloroform, or obtain a spectrum from your instructor. Interpret the NMR spectrum as completely as you can, deduce the structure of product B, and name it. Take Care! Keep diethyl ether away from ignition sources, and do not breathe its vapors. Wear gloves, avoid contact with furfural, and do not breathe its vapors. Observe and Note: Compare your observations during this reaction with your observations during the first reaction. Waste Disposal: Place the filtrate in a designated solvent recovery container. Take Care! Do not breathe the vapors of 2-butanone, and keep it away from ignition sources. Take Care! Avoid contact with CDCl3, and do not breathe its vapors. Microscale Reaction. Weigh 2.50 mmol of cyclopentanone into a 25-mL Erlenmeyer flask, and dissolve it in 3.0 mL of diethyl ether. Add 3.0 mL of aqueous 0.10 M sodium hydroxide, 2 drops of tricaprylmethylammonium chloride (or 50 mg of a suitable solid phase-transfer catalyst), and a stir bar. Cool [OP-8] the mixture in an ice/water bath for at least 5 minutes, and add Take Care! Keep diethyl ether away from ignition sources, and do not breathe its vapors. Wear gloves, avoid contact with furfural, and do not breathe its vapors. M44_LEHM3752_02_SE_C43.QXD 2/25/08 3:58 PM Page 378 378 Part II Observe and Note: Compare your observations during this reaction with your observations during the first reaction. 0.50 mL of freshly distilled furfural while stirring [OP-10]. Seal the flask with Parafilm, and stir it vigorously at room temperature for 15 minutes, occasionally swirling it in the ice/water bath to reduce pressure buildup from vaporizing ether. (Parafilm dissolves in ether, so don’t let it contact the reaction mixture.) Then let the reaction mixture stand at room temperature, with continued stirring, for 10 minutes. Waste Disposal: Place the filtrate in a designated solvent recovery container. Separation. Collect the product by vacuum filtration [OP-16], wash it [OP-26a] with two portions of diethyl ether, and air-dry it on the filter. Take Care! Do not breathe the vapors of 2-butanone, and keep it away from ignition sources. Take Care! Avoid contact with CDCl3, and do not breathe its vapors. Correlated Laboratory Experiments Purification and Analysis. Recrystallize [OP-28] product B from 2-butanone, using about 6 mL or less of the solvent. Wash the product on the filter [OP-26a] with diethyl ether, dry it [OP-26b], and weigh it. (Waste Disposal: Place the filtrate in a designated solvent recovery container.) Measure the melting point [OP-33] of product B. Record its 1H NMR spectrum [OP-40] in deuterochloroform, or obtain a spectrum from your instructor. Interpret the NMR spectrum as completely as you can, deduce the structure of product B, and name it. Exercises 1. Discuss the effect of reaction conditions on the outcome of the Claisen–Schmidt reaction, telling what reaction conditions promote the formation of each product, and why. 2. (a) What is the probable identity of the solid that was filtered from the reaction mixture in part A? How could you have confirmed its identity? (b) What percentage of the cyclopentanone that you started with in part A was converted to condensation products? (This is not the same as the percentage yield of A.) 3. Write balanced equations and detailed mechanisms for the formation of both products, A and B. 4. (a) Using balanced equations (see Exercise 3) for the reactions you carried out, calculate the atom economy and reaction efficiency of each synthesis. (b) Describe some green features of your synthesis, and any that aren’t so green. 5. Describe and explain the possible effect on your results of the following experimental errors or variations. (a) You used 10 M NaOH rather than 0.10 M NaOH in part A. (b) In part A, you rinsed the reaction flask with acetone and didn’t dry it completely. (c) You left out the tricaprylmethylammonium chloride in part B. (d) You used 50 mmol (SS) or 10 mmol (µS) of cyclopentanone in part B as well as in part A. 6. Diagram a possible phase-transfer process for the formation of product B, using the format illustrated in Experiment 24. 7. (a) Following the format in Appendix V, construct a flow diagram for the synthesis in part A. (b) Construct a flow diagram for the synthesis in part B. 8. From your 1H NMR spectra, is it more likely that your products are (Z) or (E) stereoisomers? Explain your answer. 9. An error-prone student, Mel A. Droyt, forgot to add the furfural in part A, but he recovered a small amount of liquid that distilled at 139–142°C at 20 torr and didn’t solidify on cooling.The 1H NMR spectrum of the liquid showed no signals from vinylic or hydroxylic protons. Propose a structure for this product, and write a mechanism for its formation. M44_LEHM3752_02_SE_C43.QXD Experiment 43 2/25/08 3:58 PM Page 379 Effect of Reaction Conditions on the Condensation of Furfural with Cyclopentanone Other Things You Can Do (Starred items require your instructor’s permission.) *1. As a group project, carry out part B using different phase-transfer catalysts and compare the crude yields to find out which catalysts are most effective. Suggested catalysts are tetrabutylammonium bromide, tetrabutylphosphonium bromide, cetyltrimethylammonium bromide, and 1-hexadecylpyridinium chloride. *2. Prepare some other aldol condensation products as described in Minilab 34. 3. Starting with sources listed in the Bibliography, write a research paper about the production and uses of furan, furfural, and some derivatives of these compounds. 379