Content area
Hathaway describes a modification of an experiment in which 2,6-dimethylcyclohexanone was reduced with sodium borohydride in methanol to form 2,6-dimethylcylohexanol.
Full text
In a previously published article in this Journal (1), 2,6-dimethylcyclohexanone was reduced with sodium borohydride in methanol to form 2,6-dimethylcyclohexanol (see Fig. 1). This experiment was done on the microscale, and product assignment was done by GC, according to previous literature results (2).
When this experiment was modified for the semimicroscale, the GC conditions needed to separate the three alcohol products were investigated. With a Carbowax column, the largest peak came out first, whereas with an SE-30 column, the largest peak came out second. Since order of elution varied with column polarity, a more definitive method was needed to determine the structure of the major product. An NMR analysis of these three alcohols had previously been published (3). The chemical shift of the hydrogen alpha to the OH for each of the three isomers is different enough so that proton NMR can resolve them. NMR analysis of the product mixture clearly showed the major component to be the cis-cis isomer, 1 (broad singlet at 3.50 ppm), rather than the trans-trans isomer, 2 (triplet, J = 9 Hz, at 2.66 ppm), as claimed in the previous work (1, 2). The reduction of the cis-ketone produces alcohols 1 and 2, while reduction of the trans-ketone produces alcohol 3 (doublet of doublets, J = 6 Hz and 3 Hz, 3.30 ppm).
The solvent used for the reduction in the previous articles was methanol. Because this solvent is poisonous, 95% ethanol was used as a solvent in the initial experiments, and a different ratio of 1:2 was isolated than was reported in ref 1. Therefore, a short series of solvents was investigated to determine if there was a solvent effect. For comparison, 2-methylcyclohexanone was also reduced under identical conditions.
Experimental Procedure
The assigned ketone (0.5 g) is dissolved in 10 mL of the alcohol solvent. Sodium borohydride (0.1 g) is added, and the reaction is stirred for 10 minutes. The reaction is diluted with water and extracted with two 10-mL portions of hexane. A few drops of the hexane solution are reserved for GC analysis and the rest of the hexane is transferred to a pre-weighed round-bottomed flask. The hexane is removed on a rotary evaporator, and the flask is reweighed to determine the mass of product. GC conditions: Carbowax column (30 m, 0.53 mm i.d.), column temperature = 110 oC, flow rate = 5 mL/min, injector and detector at 200 oC, 0.4 pL of hexane solution injected. Retention times: cis-2,6-dimethylcyclohexanone, 4.13 min; trans-2,6-dimethylcyclohexanone, 4.43 min; ciscis alcohol (1), 5.44 min; trans-trans alcohol (2), = 6.00 min; cis-trans alcohol (3), 8.11 min; 2-methylcyclohexanone, 4.24 min; cis-2-methylcyclohexanol, 6.34 min; trans-2methylcyclohexanol, 6.56 min. A better separation of the 2-methylcyclohexanol isomers may be obtained by lowering the column temperature.
Results
Table 1 summarizes the results. These results indicate that as the size and bulk of the solvent increase, the proportion of the trans-alcohol product increases. The reason for the solvent effect is unclear, and this effect does not appear to have been documented previously in the literature. This trend is opposite to that which occurs when 2-methylcyclohexanone is reduced by sterically hindered aluminum hydride and borohydride reagents. The more bulky reducing agents approach predominantly from the equatorial side, and cis alcohol, 1, is formed as the major product (4). Furthermore, sodium borohydride reacts slowly with methanol, and when the reaction mixture is examined by 11B NMR, the major boron-containing species are due to BH4- and B(OCH^)4- ions (5). No significant amount of alkoxyborohydride appears to exist in these reactions, so the reducing agent appears to be BH4- ion, and not an alkoxyborohydride formed from reaction of sodium borohydride with the solvent alcohol prior to reduction of the ketone.
OmegaSupplementary materials for this article are available on JCE Online at http://jchemed.chem.wisc.edu/Journal/issues/1998/ Dec/abs 1623.html.
Literature Cited
1. Garner, C. M. J. Chem. Educ. 1993, 70, A310-A311.
2. Wigfield, D. C.; Phelps, D. J. J. Am. Chem. Soc. 1974, 96, 543549.
3. Raban, M.; Lauderback, S. K.; Kost, D.J. Am. Chem. Soc. 1975, 97, 5178-5183.
4. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, 3rd ed.; Plenum: New York, 1990; Part B, pp 241-244.
5. Golden, J. H.; Schreier, C.; Singaram, B.; Williamson, S. M. Inorg. Chem. 1992,31, 1533-1535.
Department of Chemistry, Southeast Missouri State University, Cape Girardeau, MO 647014799
Copyright American Chemical Society Dec 1998