In the Laboratory
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Organic-Solvent-Free Phase-Transfer Oxidation of Alcohols Using Hydrogen Peroxide Martin Hulce* and David W. Marks Department of Chemistry, Creighton University, Omaha, NE 68178-0104; *
[email protected] Oxidation of primary and secondary alcohols is an essential functional group transformation, unlocking the powerful chemistry of the carbonyl group for the organic chemist. The use of a secondary alcohol oxidation to its corresponding ketone is nearly ubiquitous in the second-year organic chemistry laboratory curriculum. Often, the experiment is used to introduce students to both functional group analysis by infrared spectroscopy and assay of product composition by gas chromatography. Oxochromium(VI) reagents are the most important readily available oxidizing reagents (1). Aminebased oxochromium(VI) reagents (2), especially pyridinium chlorochromate (PCC) and pyridinium dichromate (PDC), have found wide use in research laboratories. Recent introduction of methods to improve yields and facilitate work-up by adsorbing such reagents on silica gel, Celite, molecular sieves, or alumina (3) reinforce their popularity. Teaching laboratory instructors, recognizing the health and environmental concerns associated with oxochromium(VI)based reagents and sensitive to the cost of proper disposal of stoichiometric heavy-metal oxidants, have turned to alternative, more environmentally benign (4) and cost-effective oxidants over the last 20 years. Most popular have been hypochlorite oxidations (5, 6 ). Other potentially attractive methods exploiting inexpensive oxidizing agents such as hydrogen peroxide (7), molecular oxygen, or air (8) have not found instructional use, owing to the use of catalysts that can be expensive when commercially available or otherwise difficult to prepare. We describe here an experiment for the organic chemistry laboratory that exploits an efficient, easy-to-use, environmentally benign, organic-solvent-free oxidation system using inexpensive phase-transfer (9) WO42᎑ catalysis and 30% aqueous hydrogen peroxide (10). Procedure The reaction is easily performed according to the scheme below using primary or secondary alcohols that are liquids or that melt below 90 °C. OH
+ H2O2 R
R'(H)
1 mol % Na2WO4•2 H2O 1 mol % [CH3(C8H17)3N]HSO4 H2O, 90 °C
O
+ R
2 H 2O
R'(H)
Oxidations are complete in one hour for benzylic secondary alcohols; other secondary alcohols require three hours. Generally, for a 4–10-mmol scale reaction, a clean 5–25-mL roundbottom flask equipped with a magnetic stirring bar is charged with 1 mol percent each of sodium tungstate dihydrate and methyltrioctylammonium hydrogensulfate (11). Hydrogen peroxide (1.1 mol equiv of a 30% solution) is added, and the contents of the flask are stirred at room temperature for 5 min. The alcohol (1.0 mol equiv) then is added, and the flask is equipped with a reflux condenser. The flask is heated at 90 °C with rapid stirring for 1–3 h and then is cooled in 66
an ice–water bath. Product ketones that are solids can be isolated by vacuum filtration and washing with ice water. If desired, solid ketones may also be isolated in the manner that is used for liquids: extraction into ethyl ether, washing with aqueous saturated sodium thiosulfate to remove any remaining hydrogen peroxide, drying through a small column of anhydrous magnesium sulfate and neutral alumina, and evaporation of the ethyl ether. If necessary, products are purified by recrystallization or by chromatography on neutral alumina. Product composition and purity are determined quantitatively by gas chromatography or 1H NMR spectroscopy. Infrared spectroscopy provides confirmation of successful functional group transformation as well as qualitative determination of product composition. Hazards Thirty weight percent aqueous hydrogen peroxide is a strong, corrosive oxidant. It should be transferred and measured using only clean glassware and should never be exposed to metal. Methyltrioctylammonium hydrogensulfate is prepared from trioctylamine and dimethylsulfate (see Instructor NotesW). Dimethylsulfate is a toxic, corrosive cancer suspect agent and mutagen that is readily absorbed through skin. It should be used only in an efficient fume hood while wearing chemically resistant gloves. Alternatively, methyltrioctylammonium hydrogensulfate can be prepared Table 1. Phase-Transfer-Catalyzed Oxidation of Alcohols Substrate
Product
Work-Up
1-Phenylethanol
Acetophenone
Extractive
Yield (%)
Purity a (%)
88 91 94
>98 96 b 94 .
1-Phenylpropanol
Propiophenone
Extractive
85 94
>98 >98
Benzhydrol
Benzophenone
Extractive
93 98
>98 >98
4-Methylbenzhydrol
4-Methylbenzophenone
Vacuum filtration
99 65 c
>98 >98
cis,trans-4-tertButylcyclohexanol
4-tert-Butylcyclohexanone
Vacuum filtration
95 89 d 60 e
94 >98 86
Benzyl alcohol
Benzaldehyde
Extractive
91 81 88 f
98 94 97
.
. .
.
a Determined
by GC analysis. The remainder was the starting alcohol. b Determined by 1H NMR spectroscopy by integration of product and substrate methyl resonances. c Yield after recrystallization from methanol. d Yield after chromatography. e 2-h reaction time. f [CH (C H ) N]HSO prepared in situ from [CH (C H ) N]Cl and 3 8 17 3 4 3 8 17 3 NaHSO4⭈H2O.
Journal of Chemical Education • Vol. 78 No. 1 January 2001 • JChemEd.chem.wisc.edu
In the Laboratory
in situ using methyltrioctylammonium chloride (Aliquat 336) and sodium hydrogen sulfate monohydrate. Results Table 1 summarizes reaction results for six representative alcohols: 1-phenylethanol, 1-phenylpropanol, benzhydrol, 4methylbenzhydrol, cis,trans-4-tert-butylcyclohexanol, and benzyl alcohol. Isolated yields and purities are remarkably good, with only small to trace amounts of starting alcohol normally present. Although benzhydrol oxidation produces solid benzophenone, this low-melting ketone did not crystallize from the reaction upon cooling, requiring the use of an extractive work-up rather than simple vacuum filtration. The reaction of slower-oxidizing cis,trans-4-tert-butylcyclohexanol usually does not proceed to completion in three hours: the small amount of alcohol remaining is apparent in the gas chromatogram of the product, with obvious broadening and lowering of its melting point. Simple chromatography on a short column of neutral alumina using petroleum ether as eluent completely removes unreacted alcohol. Finally, primary alcohols such as benzyl alcohol are smoothly oxidized to the corresponding aldehydes, with no overoxidation to carboxylic acids observed. It is interesting to note that the oxidation of cis,trans-4tert-butylcyclohexanol proceeds with measurable diastereodiscrimination. When the isolated product of the reaction is assayed for remaining alcohol after 2 or 3 hours of reaction time, an 18–20% reduction in the ratio of cis-4-tert-butylcyclohexanol to trans-4-tert-butylcyclohexanol is observed (12). The slower reaction rate of the trans isomer can be attributed to steric interactions present in an intermediate anionic tungsten peroxo complex, which undergoes dehydrogenation to form the product (13). Conclusions Organic-solvent-free oxidations of alcohols using aqueous hydrogen peroxide in the presence of tungsten and a phasetransfer catalyst provide a general, safe, simple, and costeffective means to effect this functional group transformation in the teaching laboratory. Work-up is exceptionally simple, and yields are high. Experiments can be readily designed for one or two 3-hour laboratory periods, integrating the various techniques of extraction, drying, filtration, column chromatography, gas chromatography, NMR and IR spectroscopy, and reaction kinetics, as desired.
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Supplemental Material
Written materials to be used by students, instructor notes, tables of reagents and products including sources, and gas chromatograms, IR, 1H and 13C NMR spectra of the alcohols used and aldehydes and ketones produced are available in this issue of JCE Online. Literature Cited 1. Hudlick´y, M. Oxidations in Organic Chemistry; American Chemical Society: Washington, DC, 1990. 2. Luzzio, F. A. Org. React. 1998, 53, 1. 3. Buglass, A. J.; Waterhouse, J. S. J. Chem. Educ. 1987, 64, 371. Luzzio, F. A.; Fitch, R. W.; Moore, W. J.; Mudd, K. J. J. Chem. Educ. 1999, 76, 974. 4. Green Chemistry: Frontiers in Benign Chemical Syntheses and Processes; Anastas, P.; Williamson, T. C., Eds.; Oxford University Press: Oxford, 1998. 5. Zuczek, N. M.; Furth, P. S. J. Chem. Educ. 1981, 58, 824. Kauffman, J. M.; McKee, J. R. J. Chem. Educ. 1982, 59, 862. Hill, J. W.; Jenson, J. A.; Henke, C. F.; Yaritz, J. G.; Pedersen, R. L. J. Chem. Educ. 1984, 61, 1118. Mohrig, J. R.; Nienhuis, D. M.; Linck, C. F.; Van Zoeren, C.; Fox, B. G.; Mahaffy, P. G. J. Chem. Educ. 1985, 62, 519. Straub, T. S. J. Chem. Educ. 1991, 68, 1048. Jones, C. S.; Albizati, K. J. Chem. Educ. 1994, 71, A271. Amsterdamsky, C. J. Chem. Educ. 1996, 73, 92. 6. For a review: Skarzewski, J.; Siedlecka, R. Org. Prep. Proced. Int. 1992, 24, 623. 7. Catalytic Oxidations with H2O2 as Oxidant; Strukel, C., Ed.; Kluwer: Dordrecht, 1992. 8. Markó, I. E.; Giles, P. R.; Tsukazaki, M.; Chellé-Regnaut, I.; Urch, C. J.; Brown, S. M. J. Am. Chem. Soc. 1997, 119, 12661. 9. For the use of phase-transfer catalysts in oxidations, see Lampman, G. M.; Sharpe, S. D. J. Chem. Educ. 1983, 60, 503. 10. Sato, K.; Aoki, M.; Takagi, J.; Noyori, R. J. Am. Chem. Soc. 1997, 119, 12386. 11. Sato, K.; Aoki, M.; Ogawa, M.; Hashimoto, T.; Noyori, R. J. Org. Chem. 1996, 61, 8310. 12. Assignment of the cis and trans isomers was based upon measured chemical shifts and coupling constants of their corresponding 1H NMR methine resonances; cf. Silverstein, R. M.; Webster, F. X. Spectrometric Identification of Organic Compounds, 6th ed.; Wiley: New York, 1998; pp 186, 203. 13. Venturello, C.; Ricci, M. J. Org. Chem. 1986, 51, 1599. Jacobson, S. E.; Muccigrossi, D. A.; Mares, F. J. Org. Chem. 1979, 44, 921.
JChemEd.chem.wisc.edu • Vol. 78 No. 1 January 2001 • Journal of Chemical Education
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