The Synthesis of 2'-Bromostyrene Linda Cwvari, James R, McKee, and Murray Zanger Philadelphia College of Pharmacy and Science, Philadelphia, PA 19104 Organic chemistry laboratories need not be the repositories of foul smells. Exoeriments that emolov interestine chemistry, are safe, and coincidently lead topleasant-smelt ing products are possible.' The synthesis of 2'-hromostyrene exemplifies these goals. Although not found in nature, this compound has an aromaalmost identical to that of hyacinth and is used as an odorant in soaps. T h e synthesis2 proceeds via a two-step addition and elimination sequence. The addition of bromine t o double bonds is known to proceed "anti" with the halogen atoms attaching to their respective carbon atoms from opposite sides of the planar alkene. Since commercial cinnamic acid is the trans isomer. the oroduct will be ervthro- (2R.38- or 2S.3R-) 2.3dibroio-3-phenylpropanoicacid his diastereoier has a mo of 203-204 OC. Its threo isomer melts a t 91-93 OC. The second reaction, an elimination, is both hase- and solvent-dependent and can lead to a varietv of wroducts. ~ r o v e n s t e i nand ~ Cristo14present evidence f i r mechanisms that explain these results, as outlined in the figure. The reaction of the dibromophenylpropanoic acid with base under strongly alkaline conditions will lead primarily to 2bromocinnamic acid (Path A). When no base is used or the base is carbonate, however, an "abnormal" reaction occurs in which a mole of carbon dioxide is eliminated subsequent to the loss of the benzylic bromine atom (Path C). The oroduct is a cisltrans mixture of 2'-hromostvrene. In acetone, with weak base, the elimination is stereospecific and onlv cis-2'-hromostvrene is formed (Path B). T h e use of water and carbonate in this experiment results in product via Path C. T h e product workup does not require a final distillation since I R and NMR spectra of the crude product match the standards. The carbonyl band (IR) of the original acid is absent in the final product. If students are ahle to obtain an NMR spectrum of their product, the cisltrans ratio of the product can easily be determined. Overall yields of about 50% can be expected.
' Z a W , M.:McKee, J. R. J. Chem €dm. 1988, 85, 1106.
SudbOrOugh,J. J.; Thompson, K. J. J. Chem. Soc. 1902,83,666686. Grovenstein, E., Jr.; Lee, D. E. J. Am. Chem. Soc. 1953, 75, 2639-2644. 'Cristoi, S. J.; Norris, W. P. J. Am. Chem. Soc. 1953, 75. 26452645. This synthesis can also be carried out on a lllMh scale in a test tube. After treatment with carbonate solution, ether is added to the tube, and the mixture stirred. The ether layer is removed with a pipet to another tube and dried, and the solvent is stripped. Enough product is obtained to note its characteristic aroma and to identify by IR spectrometry. Cinnamic acid is a skin irritant and is moderately toxic on ingestbn. Normal cautfon as in handling any chemical should be observed. Bromine is a toxic, corrosive poison, and special care should be taken when using it or its solutions. Rubber gloves should be worn when handling it, and it should be used in a good fume hood. 2'-Bromostyrene is moderately toxic by ingestion. (Sax. N. I. Dangerous Properlies of lndustrlal Materials. 6th ed.; Van Nostrand Reinhold: New York 1984;pp 555.579.621.) Elher that has been distilled forms peroxides readily. Save the ether only if it will be used during the same laboratory period in which it was collected.
'
[Path ~1
pn +
co2
Mechanisms forthe second-step, elimination reaction.
2,3-Dibromo-3-phenyipropanolc Acid Place 5.5 g of cinnamic acid6in a 1W-mL round-bottomed flask, and add 50 mL of solvent-grade ether. In a graduated cylinder carefully measure 10mL of a 20%(vlv) solution of hromineein ether. Add the bromine solution to the flask in several small portions. Stir, with a glass rod, after each addition. The cinnamic acid will slowly dissolve, and a dark orange solution will result. Attach the flask to a distillation head fitted with a condenser, and mount the apparatus on a steam bath. Heat gently until the ether just bails and gradually distill the ether from the flask.Continue heating until no more ether is collected. The ether may be saved for use in the second part of this expe~iment.~ Stop heating, remove the flask from the steam bath, and allow the pot residue to solidify. Add 20-30 mL of ice water to the flask, and use a spatula to break up the crystal mass Collect the crystals on a Buchner funnel, and rinse with two 10-mL portions of cold water. Dry the white crystals in a 100 "Coven. Yields of 85-90% are typical. Save a small portion, and determine the mp. Use this value to verify the stereochemistry of the product. 2-Bromostyrene6 Weigh the pmduct from the previous step, and place it in a 250mL Erlenmeyer flask. In a 100-mL beaker, weigh out an equal amount of anhydrous potassium carbonate, and dissolve it in 75 mL of water. Add the solution to the dibromocinnamie acid, and place the flask on a hot plate. Add a boiling stone to the flask, and heat the mixture to a gentle boil. Within a few minutes the solid will disapVolume 68
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pear and a light yellow oil will form. Cool the reaction mixture in an icelwater mixture, and then pour it into aseparatory funnel. Extract the aqueous mixture with 25 mL of ether, and place the ether extract in a 125-mL Erlenmyer flask. Extract with a second 25-mL portion of ether, and combine this with the first extract. Discard the aqueous phase. Dry the ether extracts over 1-2 g of anhydrous magnesium sulfate for 10-15 min. Place the dried ether solution in a small round-bottomed flask, and set up a simple distillation apparatus. Use a steam bath as the heat source, and remove all of the ether.
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Transfer the pot residue to a yield bottle using a micropipet fitted with a rubber bulh. The yield of crude product is about 505%. No further purification of the product is necessary. Note the flowery, hyacinthlike odor of the product. The identity of the bromostyrene can beverified by determining the IR spectrum of the oil. If an NMR spectrometer is available, peaks due to both the cis and trans isomers can be observed. The high-field doublet arising from the cis isomer is centered at 6.3 nnm. while the hieh-field doublet of the trans isomer is centered a t 6.8 bpm.
