In the Laboratory
Organic Reactions Involving Bromine Puzzles for the Organic Laboratory Sarita I. McGowens and Ernest F. Silversmith* Department of Chemistry, Morgan State University, Baltimore, MD 21251
Experiments having outcomes unknown to the student heighten student interest and motivation and provide a semblance of real experimentation. We have designed five experiments that present puzzles in orientation, stereochemistry, and extent of reaction. The puzzles involve the generation of bromine from hydrobromic acid and potassium bromate in acetic acid as described by Schatz (1). The equation for the reaction is CH3CO2H + 5H+ + 5Br᎑ + BrO3᎑ → 3Br2 + 3H2O + CH3CO2᎑ This method produces controllable amounts of bromine and is convenient and safe. The Puzzles
Puzzle 1: Orientation in the Bromination of 2,4-Dimethylaniline The bromination of 2,4-dimethylaniline presents an orientation problem. Amino and methyl groups are both ortho–para directors (2). Does the amino group dominate, giving 6-bromo-2,4-dimethylaniline, or do the two methyls hold sway, leading to the 3-bromo and/or 5-bromo isomer? Since 6-bromo-2,4-dimethylaniline, the anticipated product, melts at only 46 °C and is difficult to crystallize (3), it is advantageous to convert it directly to the corresponding acetanilide. 3-Bromo-2,4-dimethylacetanilide is reported to melt at 151–152 °C (4 ), while the 5- and 6-bromo isomers melt at 168–169 (4) and 200 °C (5), respectively. To solve the puzzle, 2,4-dimethylaniline is brominated by Schatz’s method (1) and the product mixture is treated directly with acetic anhydride. The final product has a melting point of 199–200 °C, clearly establishing it as 6-bromo-2,4-dimethylacetanilide. Thus, the amino group wins out! 1H NMR spectroscopy in acetone-d6 confirms the product’s structure; the coupling constant for the aromatic protons is 2 Hz, indicating that they are meta with respect to each other (6 ). Puzzle 2: Orientation in the Bromination of 2,6-Dimethylaniline The problem, once again, is whether the ortho–paradirecting ability of the amino group or of the two methyl groups predominates. The two possible acetylated products, 3-bromo-2,6-dimethylacetanilide and 4-bromo-2,6-dimethylacetanilide, reportedly melt at 136 (4) and 195 °C (7), respectively. The product obtained in our experiment melted at 196–198 °C, so the amino group rules again.
Puzzle 3: Orientation in the Bromination of Vanillin (4-Hydroxy-3-methoxybenzaldehyde) Does ortho–para direction by the methoxy group (giving 2- and/or 6-bromovanillin) win out? Or is it the combination of ortho–para direction by the hydroxyl group and meta direction of the aldehyde group (giving 5-bromovanillin)? The 2-, 5-, and 6-bromovanillins melt at 154–155 (8), 164 (9), and 178 °C (8), respectively. Our procedure yields a product that melts at 166–167 °C, in agreement with Schatz (1). It is 5bromovanillin; the hydroxyl and aldehyde groups dominated.
Puzzle 4: Stereochemistry of Bromine Addition Additions can be either syn or anti. For example, syn addition of bromine to (E )-1,2-diphenylethene would yield racemic 1,2-dibromo-1,2-diphenylethane (10), mp 113–114 °C (11), whereas anti addition would result in the meso product (10), mp 236–237 °C (11). Our product melted at 241–243 °C; hence the addition was anti, in agreement with earlier work (10).
Puzzle 5: Does Dehydrohalogenation Follow Bromine Addition? Some organic halides undergo facile dehydrohalogenation. Thus, the reaction of 1,1-diphenylethene with bromine could give 1,2-dibromo-1,1-diphenylethane, mp 61–65 °C (12), or 2-bromo-1,1-diphenylethene, mp 43–45 °C (13). Our procedure gave material melting at 41–42 °C. The 1H NMR spectrum confirms the structure as 2-bromo-1,1diphenylethene, in agreement with the findings of other workers (10). Experimental Procedure C AUTION : Hydrobromic acid is toxic and corrosive. Potassium bromate is a strong oxidizing agent and a cancer suspect agent. Acetic anhydride is corrosive and lachrymatory. The experiments should be carried out in a well-ventilated area; eye and hand protection should be worn.
6-Bromo-2,4-dimethylacetanilide (Puzzle 1) Freshly distilled 2,4-dimethylaniline (0.18 g, 0.0015 mol) (Aldrich Chemical Co.) and 2 mL of acetic acid were placed into a 25-mL Erlenmeyer flask. The mixture was stirred in an ice bath while first powdered potassium bromate (0.09 g, 0.00054 mol), then hydrobromic acid (48% or 8.7 M, 0.030 mL, 0.0026 mol), was added. The initial orange color caused by the bromine faded in 1 min. The mixture was stirred for another 4 min, and 10 mL of water
*Corresponding author.
JChemEd.chem.wisc.edu • Vol. 75 No. 10 October 1998 • Journal of Chemical Education
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In the Laboratory
was added. This resulted in a clear, faintly purple solution containing some solid (presumably 6-bromo-2,4 dimethylanilinium bromide). The mixture was transferred to a 50-mL beaker and stirred at room temperature. Two mL of 4 M NaOH was added, followed by 5.0 mL (0.053 mol) of acetic anhydride. The mixture was stirred for 30 min; during this time the original precipitate disappeared and a new one appeared. The product was isolated by vacuum filtration, washed with water, and air-dried. This gave 0.23 g (64%) of very pale tan microcrystals, mp 199–200 °C (lit. 200 °C [ 5]).
4-Bromo-2,6-dimethylacetanilide (Puzzle 2) The first paragraph of the above procedure was carried out using freshly distilled 2,6-dimethylaniline (Aldrich Chemical Co.). The resulting clear solution was stirred in a 50-mL beaker while 0.7 mL of 4 M NaOH and 2.0 mL of acetic anhydride were added. A precipitate soon formed. After 30 min, solid sodium carbonate was added, a little at a time, till effervescence stopped and the pH was 8. Vacuum filtration, washing with water, air-drying, and vacuum-drying gave 0.24 g (67%) of faintly pink microcrystals, mp 196– 198 °C (lit. 195 °C [7 ]). 5-Bromovanillin (Puzzle 3) A solution of 0.23 g (0.0015 mol) of vanillin in 3.0 mL of acetic acid was stirred at room temperature, and 0.09 g of potassium bromate, followed by 0.30 mL of 48% hydrobromic acid, was added. The mixture was stirred for 50 min and poured into 25 mL of water. The resulting mixture was stirred for 20 min and filtered by vacuum. The solid was washed with water and vacuum-dried to give 0.24 g (69%) of off-white solid, mp 166–167 °C (lit. 164 °C [ 9]). meso-1,2-Dibromo-1,2-diphenylethane (Puzzle 4) (E )-1,2-Diphenylethene (0.27 g, 0.0015 mol) and 6.0 mL of acetic acid were stirred at room temperature. Potassium bromate (0.09 g), followed by hydrobromic acid (0.30 mL), was added. The mixture was heated to 35 °C and stirred at that temperature for 10 min. The material was poured into 50 mL of water; stirring, filtering by vacuum, and air-drying gave 0.45 g (88%) of white solid, m.p. 241-3 °C (lit. 236– 237 °C [11]).
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2-Bromo-1,1-diphenylethene (Puzzle 5) 1,1-Diphenylethene (1.35 g, 0.0075 mol) (Acros Organics) was dissolved in 10.0 mL of acetic acid. Potassium bromate (0.43 g) and then hydrobromic acid (1.50 mL) were added. The mixture was boiled gently for 1 min and poured into 125 mL of water. The resulting solid was isolated by vacuum filtration, giving 1.35 g (70%) of pale yellow prisms, mp 33– 35 °C. Column chromatography of 0.30 g of this material, using alumina as adsorbent and petroleum ether as eluant, gave 0.18 g of colorless prisms, mp 41–42 °C (lit. 43–45 °C [13]). 1H NMR (in CCl4): δ = 7.3 (10H, m, aromatic), 4.0 (1H, s, vinylic). Literature Cited 1. Schatz, P. F. J. Chem. Educ. 1996, 73, 267. 2. Solomons, T. W. G. Organic Chemistry, 6th ed.; Wiley: New York, 1996; p 673. 3. Wheeler, A. S.; Thomas, R. E. J. Am. Chem. Soc. 1928, 50, 2286–2287. 4. Noelting, E.; Braun, A.; Thesmar, G. Chem. Ber. 1901, 34, 2242–2262. 5. Fischer, E.; Windaus, A. Chem. Ber. 1900, 33, 1972. 6. Pavia, D. L.; Lampman, G. M.; Kriz, G. S. Introduction to Spectroscopy, 2nd ed.; Harcourt Brace: New York, 1996; p 232. 7. Bell, F. J. Chem. Soc. 1959, 519–525. 8. Raiford, L. C.; Stoesser, W. C. J. Am. Chem. Soc. 1927, 49, 1077–1080. 9. Brink, M. Acta Univ. Lund 1965, Sect. II(6), 1–17. Chem. Abstr. 1965, 63, 8240c. 10. Jarret, R. M.; New, J.; Karaliolos, K. J. Chem. Educ. 1997, 74, 109–110. 11. Fieser, L. F. J. Chem. Educ. 1954, 31, 291–297. 12. Reichstein, T.; Mueller, H.; Meystre, C.; Sutter, M. Helv. Chem. Acta 1939, 22, 741–753. 13. Elderfield, R. C.; King, T. P. J. Am. Chem. Soc. 1954, 76, 5439–5445.
Journal of Chemical Education • Vol. 75 No. 10 October 1998 • JChemEd.chem.wisc.edu
