Experiment 7: The Synthesis of Artificial Hyacinth Odor (1-bromo-2-phenylethene), Part I

Transcription

1 Experiment 7: The Synthesis of Artificial Hyacinth Odor (1-bromo-2-phenylethene), Part I This two-step synthesis involves the following conversion: trans-cinnamic acid 2,3- dibromocinnamic acid 1-bromo-2-phenylethene (equation 1). The addition to double bonds and the elimination of alkyl halides to form double bonds are the two major reactions involving alkenes. The first is a reaction of alkenes and the second a method of synthesizing them. In this experiment we will perform the first of the two steps that lead to the synthesis of 1-bromo-2-phenylethene. This material is used in the manufacture of hand soaps since it has a pleasant hyacinth like odor. Each step is discussed in more detail in each individual part of the lab along with experimental procedures. Overall Reaction Sequence to produce 1-bromo-3-phenylethene: O trans-cinnamic acid (3-phenylpropenoic acid) Br O pyridinium bromide perbromide CH 3 CO 2 H Br 2,3-dibromocinnamic acid (2,3-dibromo-3-phenylpropionic acid) K 2 CO 3, heat (1) H H Br + Br - + CO 2 1-bromo-3-phenylethene (artificial hyacinth odor)

2 Experiment 7, Part I: Preparation of 2,3- dibromocinnamic acid from trans-cinnamic acid. INTRODUCTION The sequence is started by the addition of bromine to a double bond. This reaction, classically carried out with liquid bromine, occurs in this experiment by the use of pyridinium bromide perbromide (pyridinium tribromide). Liquid bromine is a very dangerous chemical. It is volatile, extremely corrosive and very toxic. N Br - Br 2 H pyridinium bromide perbromide On the other hand, pyridinium bromide perbromide is a solid that can be weighed out; it is less volatile and so is easier to handle. It is, however, just as toxic and corrosive as bromine so it must still be treated with great respect. The bromine is added across the double bond of 3-phenylpropenoic acid (trans-cinnamic acid). The reaction is carried out in glacial (100%) acetic acid (equation 2). O trans-cinnamic acid (3-phenylpropenoic acid) Br O pyridinium bromide perbromide CH 3 CO 2 H Br 2,3-dibromocinnamic acid (2,3-dibromo-3-phenylpropionic acid) (2) The product, 2,4-dibromo-3-phenylpropionic acid, contains 2 new chiral centers, therefore the possibility of forming four stereoisomers exists. This would be the (2R, 3S) compound and its enantiomer, which are sometimes known as erythro isomers and the (2R, 3R) compound and its enantiomer, which are known as threo isomers. As diastereomers have different physical properties including melting points, we can deduce from the melting point whether we have one of the enantiomer pairs or the other, or a mixture of all four stereoisomers. The reaction likely involves the intermediacy of a bromonium ion, a cyclic cation consisting of a (partially) positive charged bromine atom bonded to two carbons from the alkene double bond. This would explain why this reaction is used to obtain high stereoselectivity.

3 The product, 2,3-dibromo-3-phenylpropanoic acid, contains 2 new chiral centers therefore the possibility of forming four stereoisomers exist. These would be the (2R, 3S) compound and its enantiomer, which are sometimes known as erythro isomers and the (2R, 3R) compound and its enantiomer, which are known as threo isomers. As diastereomers have different physical properties, including melting points, we can deduce from the melting whether we have one of the enantiomer pairs or the other, or a mixture of all four stereoisomers. Experimental Overview: The reaction is run using glacial (100%) acetic acid as the solvent. Not only is the acetic acid used as the catalyst for this reaction, it also allows the product to be obtained via crystallization. Since acetic acid is soluble in water and the product is not, simply adding water allows us to isolate the produce from the reaction mixture. Although is might be possible to use a different solvent and a separate acid (e.g. sulfuric) as catalyst, the isolation of the product would be much more difficult. This experiment involves mixing the pyridinium bromide perbromide and transcinnamic acid in a round-bottom flask equipped with a water-cooled condenser. The flask is then heated with a heating mantle until the reactants boil. This technique is called heating under reflux. The temperature at which the reactants boil is never specified (nor determined) because the boiling temperature depends on the chemicals being heated. To get to reflux temperature, the flask is simply heated until vapors are observed in the condenser, at which time they re-condense into the reaction flask. Using this technique, none of the reactants or product(s) can escape. They are kept heated and in contact with each other at all times until the reaction is complete. The length of heating must be determined experimentally for each reaction. An insufficient heating time gives a poor yield of the desired product (incomplete reaction), but there is no point in continuing to heat the reaction once the starting material has been consumed! In this experiment, the reaction is heated at reflux for about 30 minutes, which has been found to give a reasonable yield of product. Typically, the addition of bromine to an alkene is a very fast reaction, and the boiling point of acetic acid is fairly high ( ºC) so a 30 minute reflux is sufficient. The solution is then transferred to an Erlenmeyer flask because we are about to induce precipitation of the product, and it is easier to do this in a flat-bottomed Erlenmeyer flask than a round-bottom flask. Two milliliters of acetic acid are used to rinse the reaction flask and ensure all material (or as much as possible) is transferred to the Erlenmeyer flask. Subsequent addition of the water reduces the solubility of the product to the point that the product precipitates. Adding more water will produce more precipitate, but then we run the risk of precipitating impurities, and we are left with a larger volume of solution to manipulate. This means that a compromise between purity, convenience and yield must be made. Ideally, crystallizations are carried out slowly in order to give crystals with the highest possible purity. Thus, water is added drop-wise (with stirring) to induce slow crystallization.

4 The product is then isolated by vacuum-filtration, but by-products and impurities may still be present on the surface of the crystals. In particular, there was an excess of pyridinium bromide perbromide, and this can be destroyed by washing the crystals with 10% aqueous sodium bisulfite solution. At this stage, any remaining inorganic salts and acetic acid can easily be removed by washing the crystals with cold water, which minimizes product loss. Recall that the number of washes is a compromise between product yield and product purity. For example, if the product smells of acetic acid, then additional washes will remove the acetic acid but will also dissolve some of your product. Typically, two or three washes with cold water are sufficient to provide a reasonable amount of high-purity product. Finally, we will recrystallize the product using a 1:1 ethanol:water solvent mixture. This, once again, illustrates and gives you practice in this very important purification technique and ensures that the stereoisomer identification from melting point analysis is meaningful, as we will have a pure sample. REAGENT/PRODUCT TABLE: Reagents MW (g/mol) MP (ºC) BP (ºC) Density (g/ml) pyridinium bromide perbromide N/A N/A N/A cinnamic acid N/A N/A glacial acetic acid Product(s) MW (g/mol) MP (ºC) BP (ºC) Density (g/ml) 2,3-dibromocinnamic acid (threo) or (erythro) N/A N/A EXPERIMENTAL PROCEDURE FOR YOUR SAFETY 1. Pyridinium bromide perbromide is a lachrymator (fumes may cause the eyes to fill with tears) and is corrosive contact with it may lead to severe burns. 2. Wear gloves at all times when handling pyridinium bromide perbromide. 3. Avoid inhaling pyridinium bromide perbromide. 4. Acetic acid is also a lachrymator (fumes may cause the eyes to fill with tears) and is also corrosive contact with the skin may lead to severe burns. Wear gloves, dispense in the hood and handle on the bench top underneath the minihoods. 5. Please take special care to avoid spilling reagents on the balances as they can cause significant damage to them. 1. Add 2.2 grams of trans-cinnamic acid (3-phenylpropenoic acid) to a 50 ml round bottom flask equipped with a magnetic stir bar; be sure to record the actual amounts

5 you used. 2. To the same flask add 5.3 grams of pyridinium bromide perbromide (cautioncorrosive), followed by 17.5 ml glacial acetic acid (caution - corrosive). Again, be sure to record the actual amounts you used. 3. Place your hotplate on the bench top, set the heating mantle in the center of the hotplate (make sure the hot plate is off!). Position your round-bottom flask in the heating mantle and firmly clamp in place at the neck of the round-bottom flask. Attach a reflux condenser to the 50 ml flask (second clamp at the top of the condenser) and turn on water, making sure that the water is flowing in the bottom and out the top. A mini-hood should be positioned above the opening of your condenser to prevent you from smelling or inhaling any fumes. 4. Start the stirrer at a setting of 5 or 6 (stirring prevents bumping!) and set the temperature control to 119 on the Variac. 5. Allow the mixture to reflux for 30 minutes after it has started to boil. Be sure to write observations during the procedure, noting in detail how the appearance of the reaction mixture changes over the course of the reaction. 6. After 30 minutes of refluxing, cool the mixture to room temperature in a cool water bath (use a beaker for cool water bath). Do not remove the condenser until the reaction mixture is cool. 7. Carefully transfer the reaction mixture to a 50 ml Erlenmeyer flask. Complete the transfer by rinsing out the reaction flask with an additional 2 ml of glacial acetic acid and adding it to the Erlenmeyer flask. You will need to transfer the magnetic stir bar as well. 8. Place the Erlenmeyer flask on your stirring hot plate and secure it with a clamp to prevent it from falling over. 9. Obtain 5mL of 10% aqueous sodium bisulfite. To the rapidly stirred (set at 6-7) reaction mixture, add the bisulfite solution dropwise over the period of 2-3 minute until the yellow color disappears. If, after 5 ml has been added and the yellow color persists add more dropwise until the color is gone. If the yellow color is gone before all of the 10% sodium bisulfite is added, you do not need to add the remaining. (Record observations and how much solution needs to be added to cause the color change.) 10. To the rapidly stirred (stirrer set at 6-7) reaction mixture, slowly add 10 ml of cool

6 water over a period of 5 minutes. Then, place it in an ice bath for at least 5 minutes. 11. Collect your crude product by vacuum filtration using a Büchner funnel. Rinse your flask with several portions of ice-cold water to ensure complete transfer of your solid onto the filter. 12. Dispose of the filtrate into the designated waste container, then reassemble the filtration apparatus and continue to pull air through your product for 5 minutes to dry it further (the product will dry faster over an empty filtration flask). While it is drying, obtain 50 ml of 1:1 ethanol:water solution in an Erlenmeyer flask for recrystallization and begin warming it on your hotplate set to Obtain the crude mass of your product, using a weighing boat, and transfer it to a 125 ml Erlenmeyer flask for recrystallization. 14. Recrystallize your crude solid from hot 1:1 ethanol:water you will need approximately 10 ml of solvent per 1g of material, but remember to add it in small portions until it has all just dissolved. After you add the first portion, place the flask on the hotplate to keep the solution warm. 15. Once all the solid has dissolved, allow it to cool to room temperature and then in an icebath to fully crystallize. While this is happening, clean and set up your Büchner funnel for vacuum filtration. 16. After recrystallization, is complete, collect your product by vacuum filtration and air-dry it. 17. Leave the product in the top of the Büchner funnel, and carefully place it in the bottom of your locker to dry until next lab period. After the crystals have thoroughly dried, obtain the final mass. Weigh a clean dry sample vial with a cap. Transfer your product using a wide-mouth powder funnel and reweigh the vial and cap, with the product inside. Then obtain a melting point range of your product (do one fast run, one slow run). Submit your properly labeled product to your instructor upon completion of the lab. Digimelt Settings: Fast Run: START temp: 60ºC, RAMP rate: 20ºC/min, STOP temp: 210ºC. If nothing melts by 100ºC, reset the START temp to 160ºC and continue melting the same sample. Slow Run: START temp: (reset as appropriate), RAMP rate: 2ºC/min, STOP temp: 210ºC. CALCULATIONS

7 1. Calculate the moles of pyridinium bromide perbromide used. 2. Calculate the moles of trans-cinnamic acid used. 3. Determine which component is the limiting reagent. 4. Calculate the theoretical yield of 2,3-dibromocinnamic acid (in grams) 5. Calculate the percent yield of 2,3-dibromocinnamic acid. 6. Calculate the percent recovery of 2,3-dibromocinnamic acid. WASTE DISPOSAL Place the filtrate contained in the filter flask in the bromination filtrate waste bottle. All filter paper waste can be placed in the trashcan.