In the Laboratory
the microscale laboratory
Mini-scale Oxidation/Reduction in Organic Laboratory Course: 4-Nitrobenzaldehyde/ 4-Nitrobenzyl Alcohol Douglass F. Taber, Yanong Wang, and Sebastian Liehr Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716
Oxidation of an alcohol to the aldehyde or ketone, and corresponding reduction back to the alcohol, are two of the most common transformations of preparative organic chemistry. As such, they have a place in the undergraduate laboratory course. We have found the exercises currently available in laboratory texts (1–3) to be deficient in several ways: the oxidized products [camphor (1a), cyclohexanone (1b)] are volatile and difficult to isolate, and do not visualize on TLC. While camphor is a solid, it is difficult to isolate and crystallize. We have found a much more satisfactory combination in 4nitrobenzyl alcohol (I) and 4-nitrobenzaldehyde (II) (see equation below). Both are crystalline, neither is volatile, and both are strongly UV-absorbing, so they visualize well on TLC. H
CH2OH
O
PCC
Figure 1. Chromatography column.
NaBH4
NO2
I
NO2
II
HAZARD: All chromium residues should be considered to be mutagenic. In the workup of the oxidation, the chromium residue is precipitated and removed by filtration. The filtered solids should be collected and disposed of properly. Experimental Procedure
Oxidant Preparation The oxidant was prepared by combining equal weights of pyridinium chlorochromate (4), sodium acetate (5a), and activated 4 Å molecular sieve (5b) and grinding the mixture into a fine powder with a mortar and pestle. Oxidation Suspend the oxidant (1.70 g, 2.64 mmol) in methylene chloride (10 mL) with magnetic stirring in a 50-mL Erlenmeyer flask and add 4-nitrobenzyl alcohol (200 mg, 1.31 mmol). Stir the mixture for 30 min at room temperature. TLC monitoring (30% ethyl acetate in petroleum ether, visualize with UV) should indicate that the reaction is almost complete. Add forisil (2 g) to the reaction mixture and stir vigorously for 5 min. Filter the reaction mixture using an additional 10 mL of ether. Set aside 0.5 mL of the filtrate for reduction (see below). Dispose of the solid oxidant waste in the designated bottle. Transfer the rest of the filtrate to a round-bottom flask, add one gram of coarse silica gel (60–200 mesh) and evaporate the suspension to dryness on a rotary
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evaporator. Pack a small amount of glass wool into the bottom of a 2-cm i.d. by 20-cm chromatography column (Fig. 1), then secure the column with a clamp. To the column, add one gram of sand to cover the glass wool followed by 5 g of silica gel (230–400 mesh). Tap the column to settle the packing and add the one gram of silica gel with the product on it to the top of the column. Cover with an additional 1 g of sand. Elute the column with 15% methylene chloride in petroleum ether, collect 10mL fractions in test tubes, and check each one by TLC. Combine the fractions containing pure aldehyde in a tared round-bottom flask and concentrate on the rotary evaporator. Typically, one receives about 170 mg of product (85%) as a white solid. The melting point for the pure aldehyde is 185–187 °C.
Reduction (microscale) Dilute the 0.5 mL of filtrate from above (impure aldehyde) with 0.5 mL of ethanol. Run the TLC. Add 30 mg of sodium borohydride to the reaction mixture and stir at room temperature, monitoring by TLC. The reaction goes to completion very quickly. Compare the Rf values of the compounds in the reaction mixture by TLC with the aldehyde and the alcohol. Literature Cited 1. (a) Camphor: Wilcox, C. F., Jr. Experimental Organic Chemistry; Macmillan: New York, 1988; pp 371–372. (b) Cyclohexanone: Williamson, K. L. Macroscale and Microascale Organic Experiments; D. C. Heath: Lexington, MA, 1994; pp 343–344. The latter procedure also uses pyridinium chlorochromate, but following a more cumbersome procedure than that outlined here. 2. Recent reports on oxidation in the organic teaching laboratory have focused on NaOCl and enzymatic oxidation: (a) Mohrig, J. R.; Nienhuis, D. M.; Linck, C. R.;
Journal of Chemical Education • Vol. 73 No. 11 November 1996
In the Laboratory
3. 4. 5. 6.
Van Zoeren, C.; Fox, B. G.; Manhaffy, P. G. J. Chem. Educ. 1985, 62, 519. (b) Straub, T. S. J. Chem. Educ. 1991, 68, 1048. (c) Kafarski, P.; Otterbreit, B.; Wieczorek, P.; Pawjowicz, P. J. Chem. Educ. 1988, 65, 549. For a recent report of the use of NaBH4 reduction in the organic teaching laboratory, see Jones, A. G. J. Chem. Educ. 1988, 65, 611. Corey, E. J.; Suggs, J. W. Tetrahedron Lett. 1975, 2647. (a) Maloney, J. R.; Lyle, R. E.; Saavedra, J. E.; Lyle, G. G. Synthesis 1978, 212. (b) Herscovici, J.; Antonakis, K. J. Chem. Commun. 1980, 561. For an earlier use of silica gel column chromatography in the undergraduate teaching laboratory, see Taber, D. F.; Hoerner, R. S. J. Chem. Educ. 1991, 68, 73.
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