Synthesis of a Bromohydrin An Experiment Demonstrating Markovnikov Addition Diane J. Porter, Andrea T. Stewart, and Carl T. wigal1 Lebanon Valley College, Annville, PA 17003 Regiospecific electrophilic addition to alkenes is a major issue in organic chemistry. The fundamental principle of regiospecific electrophilic addition is Markovnikov's rule. Despite the significance of this principle, the only reported experiment for organic chemistry t h a t demonstrates Markovnikov addition is oxymercuration ( I ) ,which generates mercury metal. We have developed a microscale experiment based on t h e bromohydrin derived from l-methylcyclohexene; i t alleviates the generation of noxious material yet demonstrates unequivocally the fundamental concepts of Markovnikov addition. This experiment can be conducted in a single lahoratory period and is simple in both procedure and equipment needed. Theory Markovnikov's rule (2) originally stated that the electrophilic addition of HX to a n unsymmetrical alkene leads to attachment of the hydrogen to the less substituted carbon. In a more general application, the rule states that in the addition of a n unsymmetrical reagent to a multiple bond, the positive portion of the reagent is introduced a t the less-substituted carbon. This regioselectivity has been attributed to formation of the more stahle, positively charged intermediate. Bromohydrin formation resulting from addition of HOBr to a n alkene is regiospecific in the absence of steric restrictions (3). The mechanism of bromohydrin formation occurs in two steps a s shown in Figure 1.Electrophilic addition of the positively charged bromine atom to the alkene results in formation of the bromonium ion intermediate. Nucleophilic addition of water or hydroxide to this intermediate results in bromohydrin formation. In the case of an unsymmetrical bromonium ion, the hydroxyl group is 'Author to whom correspondence should be addressed.
introduced a t the more-substituted carbon, which is best able to support positive charge in accordance with Markovnikov's rule. Experimental Procedure In a 5.0-mL conical vial equipped with a magnetic spin vane were placed N-hromosuccinimide (NBS) (350 mg), water (1.0 mL), and tetrahydrofuran (750 FL). Added to this heterogeneous mixture was l-methylcyclohexene (240 FL). The reaction mixture was allowed to stir a t room temperature until no solid NBS was observed in the colorless solution (about 10 m i d . If solid NBS was present or a yellow color persisted, additional l-methylcyclohexene was added in 10-pL increments until the solution became colorless. The resulting mixture was diluted with water (2.0 mL) and allowed to stir for a n additional 2 min. The spin vane was removed, and the bottom layer containing the bromohydrin was transfemed to a vial. The wet, crude bromohydrin was dried with anhydrous magnesium sulfate and purified by dry-pack column chromatography. Purification by Dry-Pack Column Chromatography The column was prepared by placing 500 mg of silica gel (Merck, 230400 mesh) in a Pasteur pipet that contained a
Figure 1. The mechanism of the bromohydrin reaction.
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transferred to the column. The liquid was allowed to drain until the top of the silica gel was free of liquid. The column was developed w i t h 3.0 m L of CHzClz, which was forced through the column with the aid of a pipet bulb and collected i n a tared vial. The solvent was removed until a constant weight was obtained. The clear viscous liquid (30-80%) gave the following spectral data. IR (liquid film) 3420, 2937, 2862, 1446, 1378, 1329.1206.1134.1028.964.926.734.687.460 em-' MS m/z'(rela&e iniensity) (94 (3), 192 (3), 179 (3),177(3),151(2),1 4 9 W 138 (I),136 (11,113(59L 95 (30),71(34),43 (75). 'H NMR (CDCI,, 250 MHz) 6 1.36 ( 6 , 3 H), 1.401.53(m,2H),1.68-2.01(m,5H),2.15(~,1Hl2.232.29(m.lH).4.16(dd.J=43.11.5Hz.lH1.
0-001
4600
35b0
30b0
25b0
20b0
15b0
cm,
10b0
Discussion The crude product is a binary mixture of 2bromo-l-methylcyclohexanoland succinimide ) 5 1.0 FA a s determined by GC-MS.~ Dry-pack column chromatography effectively separates the succinimide from the b r o ~ n o h ~ d r iA n .typical ~ 50 60 70 80 90 M~sdChsr~c student yield is -60% after chromatography n c d m d c Rod"C1 being the with 2-bromo-l-methylcyclohexanol only observed addition product. Product characterization can be accomd i s h e d on various levels of soohistication. Students who have access to instrumental methods can use IR analvsis and GC-MS. As shown i n Figure 2, the byomohydrin shows IR absorptions a t 3420 a n d 1134 cm-I corresponding to the O-H and C-0 stretching freouencies (4). The Dresence of hromine is evident from the mass spectra, which show peaks of m l z = 192 and 194 of almost equal intensity characteristic of the natural abundance of 7 9 ~ arn d "Br (4). I n lieu of instrumental methods, students can use a simple qualitative test? The presence of the hydroxyl group can be determined by the ceric nitrate test (6). Alcohols with fewer than 10 carbons give a 4.0 E6 positive test a s indicated by a color change from yellow to red (6).The presence of bro2.0 E6 mine can be determined bv usine the silver ni9 1.0 E6 trate test (6). A positive &st is rndicated by a silver halide orecioitate. The bromohvdrin re4 6 8 10 Tim. mi". acts immediately i n both cases to give positive Flg~re2 (a) IR spectrum of 2-oromo-l-methycyclohexanol: (0) mass spectrbm of s ~ c -tests. rcnochcmistry of addition is deterc n mue: (c)Iota #oncnromatograph of cnde proam: (d) mass spectrm of 2-bromo-t"'led bv lhe Jones oxidation lest whch,ln metnv, cvc onexano,: le, Iota on chromaroaraon of oroddct after coldmn , t h ~ scase, d~fferentiatesa secondary alcohol chromatography. tanti-Markovnikov addition, from a trrtiaw alcohol (Markovnikov addition). Students c& out the Jones oxidation test on secondary and tertiary alcohol glass-wool plug. The column was loadedby transferring standards along with the obtained bromohydrin. The prodthe dry, crude bromohydrin from the vial to the column usuct, 2-bromo-l-methyleyelohexanol,gives a negative Jones ing a Pasteur pipet. The vial containing the drying agent oxidation test that is consistent with the regiochemistry of was rinsed with 4 drops of CHzClz, and the rinse was also Markovnikov addition. Scan 131 (4.127 min.) of Succinimidc
. .
'GC ana yss (HP-1, 25 m x 0 2 mm; solvent de ay: 2 0 m n: mtla lemperatdre. 40 C, ramp rate 200 'C m n, gave tne following reten1 on times. s x c n mde. 4 12 m n: 2-oromo-1-metnylcycohexano, 4.56 min. 30ver-developingthe chromatographic column results in an IR absorption at 1715 cm-'corresponding to the carbonyl stretch of succinimide. However this will not affect the results of the aualitative tests. %I q~al~tat~ve tosts werc carr eo 041 as aescr oea n ref 5 D oxane was Jsed as a coso vent fortne cerc n Irate test to ncrease s o l ~ biy
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Journal of Chemical Education
Literature Cited 1. Oibbs, R.; Weber, W. P J Chsm.Educ 1971.48.477, 2. Markounikov, W A n n 1870, 153,256. 3. Dalton, D. R.;Dutta V. P:Jones, D.C.J. Am. Chrm.Soe 1968,9D, 5498. 4. Silverstein. R. M.;Bassler,G. C.: Moni1l.T.C . S m c t m m e t ~ I d e n l i ( i r o l i o nofOwanic Compounds;Wiley: New York, 1991. 5 . Mayo. D. W.; Pike, R. M.: Butcher, S. S. Miemsale Orgoniehborotory, ,dad.: wi1ey: New York, 1994. 6. Shriner R. L.; Fuaon. R. C.;Momill. T. C. The Syslemafb Identifieation of Organic Compounds,66th ed.; Wiley: New Ywk. 1960.
