Experiment 5 : The Diels-Alder reaction

Transcription

1 42 Experiment 5 : The Diels-Alder reaction Experiment 5 Introduction The reaction of conjugated dienes with alkenes to give 6-membered rings is known as the Diels- Alder reaction, named after Otto Diels and Kurt Alder who received the Nobel Prize for Chemistry in 1950 for discovering this highly useful reaction. It is probably the best known cycloaddition reaction and a very powerful way of making 6-membered rings in high yield and with high stereospecificity. Diene CO 2 R Diels-Alder reaction CO 2 R Dienophile Cycloaddition product Over the years, the Diels-Alder reaction has been used extensively in the synthesis of complex natural products. The synthetic scope and the theory behind cycloadditions will be discussed in more detail in your Organic Reactions I + II lectures. The reaction mechanism of a Diels-Alder reaction involves no charged or radical intermediates but proceeds in a single (= concerted) step as indicated by the three simultaneous curly arrows in the scheme above (further reading: Clayden, Organic Chemistry, pp ). The Diels-Alder reaction proceeds most readily if the alkene (also called the dienophile ) is electron-deficient, the diene is electron-rich and/or has a fixed cisoid conformation, like cyclopentadiene. In this experiment, you need cyclopentadiene which has been prepared for you by the thermal cracking of dicyclopentadiene, a commercially available dimer of cyclopentadiene. A small bottle or vial of cyclopentadiene is kept in an ice bath during lab hours and stored in the freezer between lab sessions. Cyclopentadiene dimerises (by a Diels-Alder reaction) within a few hours at room temperature; beware that this experiment does not work if cyclopentadiene has gone off. Cyclopentadiene is quite volatile (its b.p. is C) and, due to contamination with dicyclopentadiene, has a disagreeable smell and should only be used in a fume cupboard. PRE-LAB EXERCISES Dicyclopentadiene a. Watch the following video in preparation of your experiment: Recrystallisation, COSY, HSQC b. Do the pre-lab webtest for Experiment 5+8 on VISION. c. Prepare a table of reagents in your lab book.

2 43 Procedures Safety Notes Cyclopentadiene (and dicyclopentadiene): Highly flammable liquid and vapour; harmful by inhalation and if swallowed; irritating to eyes, respiratory system and skin; toxic to aquatic life with long lasting effects. The compound has a very disagreeable odour (due to the presence of dicyclopentadiene) and must always be handled in the fume cupboard. Maleic anhydride: Harmful if swallowed; causes severe skin burns and eye damage; may cause an allergic skin reaction. May cause allergy or asthma symptoms or breathing difficulties if inhaled. Ethyl acetate: drowsiness and dizziness. Highly flammable liquid and vapour; causes serious eye irritation; vapours may cause Petroleum ether: Highly flammable liquid and vapour make sure there are no naked flames nearby; vapours may cause drowsiness and dizziness; suspected of damaging fertility or the unborn child; harmful: may cause lung damage if swallowed; toxic to aquatic organisms. Concentrated sulfuric acid: Causes severe skin burns and eye damage. O O H 2 O H 2 SO 4 5A 5B 5C C 5 H 6 (66.1) d 0.80 O Maleic anhydride C 4 H 2 O 3 (98.1) 5A Diels-Alder reaction of cyclopentadiene and maleic anhydride USE A FUME CUPBOARD FOR THIS STEP. Place powdered maleic anhydride (30.0 mmol) in a conical flask and dissolve it in dry ethyl acetate (10 ml) with gentle warming. Add dry petroleum ether 14 (10 ml) and cool thoroughly in an ice water bath. Leave it there even though some crystals may appear. With a graduated plastic pipette take out cyclopentadiene (2.9 ml, 35 mmol) 15 from the storage container INSIDE A FUME CUPBOARD. Add the cyclopentadiene to the maleic anhydride solution (or suspension) with swirling and cooling. 16 If you are thinking about 14 Use petroleum ether with a boiling range of C. 15 What is the reason for using an excess of cyclopentadiene? 16 If you are having problems getting maleic anhydride dissolved in the ethyl acetate/pet ether mixture, you can carry out the reaction in ethyl acetate alone. In this case, add the pet ether once you have allowed the maleic anhydride and cyclopentadiene to react for 30 minutes.

3 44 taking the pipette out of the fume cupboard, rinse it first with acetone in the fume cupboard because cyclopentadiene and its dimer have a highly disagreeable odour. Heat the cyclopentadiene/maleic anhydride mixture until everything that will dissolve has done so, filter if necessary, and leave undisturbed for crystallisation. This gives product 5A. 5B 5C Hydrolysis of 5A Place 5A (2 g) and deionised water (25 ml) in a conical flask. Swirl and boil until all the oil has dissolved. Allow the solution to cool to room temperature. Let the crystals form spontaneously on slow cooling. 17 Finally, cool in an ice water bath and collect product 5B. Dry the crystals thoroughly. When measuring the melting point note any observations (particularly if your heating rate is slow). Reaction of 5B with acid Put 5B (0.5 g) and concentrated sulfuric acid (2.5 ml) in a conical flask and heat gently until all is dissolved. Cool in an ice water bath and add small pieces of ice until the total volume is about 10 ml. Heat to boiling and allow the solution to simmer for 5 minutes. Cool well, scratch the flask to induce crystallisation, and allow the product to crystallise. Collect product 5C, and recrystallise it from water. It will be up to you to find out how much water is needed for optimum results. If you are unsure how to do a recrystallisation properly, watch the online video on recrystallisation. Dry your product thoroughly (air-drying requires at least 2 days). Results & Discussion (a) Analyse the spectroscopic data for your product. NMR spectra are available online; mass spectra of 5A and 5B are shown on the following pages. When tabulating your NMR data, draw a 3D structure (or paste a Chem3D model) of your product into your report and indicate clearly the chemical shift of each group. Note: The structures of 5A, 5B and 5C are very much three-dimensional and you will find molecular models very helpful in working out what is going on. For a computer model of your product, simply paste a ChemDraw structure of your structure into Chem3D, then do an MM2 minimisation by pressing the icon. 17 If no crystals appear, scratch with a glass rod at the air water interface.

4 45 MS data from SDBSWeb: (National Institute of Advanced Industrial Science and Technology) 5D (b) 2D NMR analysis of 5B The 1 H NMR spectra of 5A and 5B are more complicated than most that you will have seen before, not the least because most of the signals are higher-order multiplets. You will therefore find the 2D NMR spectra on the following pages quite useful for your analysis. An HSQC correlates a carbon signal (plotted vertically) with its directly attached proton(s) (on the horizontal axis). Correlation is through a single C H bond, which will allow you to assign unequivocally all non-quaternary 13 C NMR signals since you have already assigned all signals in the 1 H NMR spectrum.

5 (c) 46 A COSY shows which pairs of protons are coupled. The off-diagonal peaks are the really important ones since these occur only when a proton on the horizontal axis and one on the vertical axis couple with each other. The NOESY spectrum looks at a first glance very similar to a COSY. However, its off-diagonal peaks indicate pairs of nuclei in a molecule that are close together in space no matter whether they couple with each other or not. Note that the two protons on the CH2 group are diastereotopic and have slightly different chemical shifts. The NOESY evidence should allow you to assign them without ambiguity. Use the 2D NMR spectra to fully assign all 1 H and 13 C NMR signals of 5B. In your report draw a 3D structure (or, better still, use a Chem3D or HyperChem model) of your product and write the chemical shift of each C or H. Compound 5C is an isomer of 5B and the two compounds have the same molecular formula. With the help of the IR evidence, identify which functional group is present in 5C that is not found in 5B. It is not possible to completely assign the NMR signals for 5C (except for a few signals) without 2D NMR spectra, and you are not expected to do so. Why is the 1 H NMR spectrum of 5C (available online) so very much more complex than those of 5A or 5B? What does the formation of 5C tell you about the stereochemistry of the Diels-Alder product 5A? Can you confirm the stereochemistry of 5B using the evidence from the NOESY? (d) Write a curly-arrow mechanism for the formation of 5C. These cross-peaks are red-coloured in the DEPT-edited HSQC.

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