An Organic Laboratory Experiment

of the toxic and corrosive bromine. TBABr, + C6H,-CH=CHZ -r C6H5-CHBr-CHzBr + TBABr. 1. 2. 3. 4. The reaction ofhromine in methanol with an alkene pen...
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Regioselective Methoxybromination of Styrene Using TBABr3 in Methanol An Organic Laboratory Experiment Jacques ~erthelot,' Yamina Benarnrnar, and Catherine Lange Universite Pierre et Marie Curie, Laboratoire de Chimie Organique Structurale 2, CNRS, ERS 72, Boite 45, 4 Place Jussieu, 75252 Paris Cedex 05, France Bromination of organic compounds is a common process of considerable interest in synthesis and teaching. In a previous paper (I)we reported the simple and easy bromination of styrene i n chloroform, using tetrabutylammonium tribromide (TBABrd, which lacks the drawbacks of the toxic and corrosive bromine. TBABr, + C6H,-CH=CHZ -r C6H5-CHBr-CHzBr + TBABr 1




The reaction ofhromine in methanol with an alkene penerally results in a mixture of dibromo and methoxybr~;mo adducts ,21. Methoxybrom~nationis un interesting model of dissymetric addition on two adjacent carbons, and styrene has often been used to study its regioselectivity. We describe here a new procedure using TBABr3 i n methanol to carry out methoxybromination. I t easily can be used as a n organic laboratory experiment.

Experimental To 1.2 mL (1.3 x 10" moll of styrene in 100 mL of pure methanol, a t room temperature, in a 250-mL Erlenmeyer moll of TBABr3 in about 10 flask was added 3g (1.3 x min with magnetic stirring. Stirring was continued for 5 min after the addition while the red solution changed to yellow. The solvent was evaporated using a rotary evaporator with a bath temperature not exceeding 40 OC. The residue was dissolved in 50 mL of diethyl ether, poured in a 100-mL separatory funnel, washed with water (15 mL), then with an aqueous 5% sodium thiosulfate solution (2 x 15 mL) and finally with water (15 mL). The ether layer was separated, dried over sodium sulfate, and filtered. After evaporation of the solvent a colorless liquid was obtained. By adding some drops of ethanol the dibromide 3 crystallized. The white crystals were separated by filtration (0.17g, yield 5%, mp 72 OC). The purity was checked by thin-layer chromatography (TLC) on silica gel (diethyl etherheptane: 16184; Rfi 0.61, which showed a sin le well-defined spot. The structure was confirmed by its 5H NMR spectrum (80 MHz, CDCls), 6 = 7.45 (s, 5H), and a deceptively simple ABX system (4 lines in the X part centered a t 6 = 5.1 and 3 lines in the AB part centered a t 6 = 3.9) (3). Methanol was evaporated from the filtrate. A colorless oil was obtained. This crude metboxybrominated com'To whom correspondenceshould be addressed. 850

Journal of Chemical Education

pound 5 (2.6 g, yield 95%) was found to be pure a s evidenced by TLC (same eluent a s revionsly, Rt: 0.5). Its structure was confirmed by i t s PH NMR spectrum (80 MHz, CDCl3) S = 7.35 (6, 5H), a deceptively simple ABX system (4 lines in the X part centered a t 6 = 4.3 and 3 lines in the AB part centered a t 6 = 3.45) and 3.3 (s, 3H). The total yield of products 3 and 5 based on the initial amount of styrene is 97%. Discussion Compounds 3 and 5 are identical to authentic products a s evidenced by the comparison of 'H NMR spectra and mass spectra and their Rfin TLC. Samples of 3 and 5 were prepared according to refs 1 and 2. Only regioisomer 5 was found; its isomer CsH5CHBrCHz(0Me) is never obtained using TBABr3 in methanol. Some isolated examples have been reported in literature where preponderant methoxybromination is observed but yields are often low (2). The methoxybromination of styrene using methylhypobromite leads to a mixture of the two regioisomers C6H5-CH(OMe)CH2Brand C6H5-CHBrCH2(0Me) with a low amount of C6H5CHBrCH2Br,and their ratio depends on the experimental conditions (4). The mass spectrum of 3 is typical of a dibrominated molecule: Mf a t m/z 266-264-262 (triplet i n the ratio 1 2 1 ) ; (M-Br)' a t mh 185-183 (doublet 1:1), and (M-2Br)' a t m/z 104 (base peak). The structure of 5 is confirmed by its mass spectrum: M+ a t m/z 216-214 (doublet 1:l) IM-Brlt a t mlz 135.. and ICsH5CHtOMe,l'at m z 121 (base The advantages of our experiment are the following. The rencmnts, styrene, and TBABr3,are cornrnerc~allgnvailahk dnniscn Chimwa : TBABr, is nn anhydrous solld, srnble, and not taxir Its handlmr is safe and easy, cantrnrv to bromine. The reaction is conveniently run at room temperature and results in a very high yield. The reaction products are obtained pure (as confirmed by TLC) and are easily characterized by their 'H NMR spectra. ~


Additional Experiments Many preparative reactions that would be otherwise attractive are ruled out for use in the undergraduate organic chemistry laboratory due to long reaction times that lead to student boredom and inactivity. This is not the case of our methoxybromination reaction, which requires only 15 min of stirring. Furthermore this reaction can be camed out a t the same time as the simple bromination by TBABr3 in CHC13, which is somewhat longer (50 min). The reaction products can be compared, and the students have here a n interesting example of a reaction that leads to different results according to the solvent used.

The progress of both reactions can be monitored by TLC (same eluent, styrene; Rf:0.8) giving a n additional application of this important technique in the undergraduate organic laboratory If a mass spectrometer is available, the peaks due to compounds 3 and 5 can be monitored and explained. Addition Mechanism Using TBABr3, the addition of two bromine atoms to double bonds i s a n t i ( I ) . The methoxybromination by TBABr3 in methanol gives only the Markovnikov isomer. This suggests that the addition mechanism is ionic. In a previous work, we showed that the tribromide ionis linear; the two terminal bromine atoms bear a negative charge, and the central bromine bears a positive charge (5). The first step is possibly a charge-transfer complex between styrene and B r 3 (61, followed by the formation of a cyclic zwitterion evolving to a stable benzylic carbocation. This latter can be attacked by the nucleophilic moieties present in the medium (MeOH or Br-) and forms the dibromide 3 or the methoxybromide 5. I n a methanolic solu-

tion, where methanol is the preponderant nucleophilic entity, 5 is the major product. Conclusion The methoxybrominated regioisomer 5 is easily obtained with a very high yield by using TBABr3, which is stable and nontoxic, in methanol under mild conditions. Literature Cited 1. Berthelot, J.: Foumier, M. J. Chem. Educ. 1988.63. 1011. 2. Viskwekams, L. C.; Walia, J. S. J Indion Chsm Soc. 1976.53, 156162. 3. Pouchert, C.J. ThaAIdrich LibrovofAMRSpecfm. 2nd ed.;AldrichChemical Company, 1983: Vol 1, p 776. 4. Heasley, V L.:Flye, C. L.: Hearley, G. E.; Martin. K. A ; Redfield. D.A ; W~ldalday,P S. lllmhedmn I a t t 1370,18.1573-1576. 5. Berthelof, J.;Guefte. C.; Desbene, P L.: Basselier, J.J.; Chsquin, P.;Mapure. D. Can. J. Chem. 1990,68,464470. 6. Bellmi, G.;Chiappe,C., Mamni, F J A m Chom. Soc 1987, 109,515522.

Volume 72 Number 9 September 1995