Chromium VI -Based Oxidants

Pioneering work in the synthesis of 8,12-eudesmanolides from santonin was carried out by Yamakawa and coworkers [47], These authors reported an allylic oxidation, with Cr(VI)-based oxidants, of methyl 3-oxoeudesm-1,4,6-trienoate (291) to give the corresponding 8-oxo-compound 294. Compound 291 was prepared from santonin (1) in a multi-step synthesis in 20% overall yield. Subsequent allylic oxidation of 291 with chromium reagents proceeded in low yield and the 8-oxo-compound (294) obtained in this way presented further difficulties when reduction of the carbonyl group at C(8) into a hydroxyl group was attempted. 

Vigorous oxidation leads to the formation of a carboxylic acid but a number of meth ods permit us to stop the oxidation at the intermediate aldehyde stage The reagents most commonly used for oxidizing alcohols are based on high oxidation state transition met als particularly chromium(VI)... 

Attempts of Sanko and Stefanovskii to make direct measurements of the oxidation potentials of couples involving these chromium species were not successful. An estimate of the potential of the Cr(VI)/Cr(V) couple was given by West-heimer, based on the equilibrium between chromium(VI) and iron(II), viz. 

Various oxidizing agents based on chromium(VI) have been used to oxidize 2° alcohols to ketones. 

An interesting alternative to the use of chromium(VI) oxidants for the conversion of 1 to 2 involves the use of a low-valent iron reagent prepared in situ by the action of hydrogen peroxide on an iron(II) complex of 1 (73). Vinblastine (as the free base) is treated with 2 equiv of perchloric acid in acetonitrile at -20°C. Ferrous perchlorate is then added, followed by the addition of excess 30% hydrogen peroxide. Work-up of the reaction mixture with a saturated solution of ammonium hydroxide gives 2 in yields of 35-50% after chromatography. 

All of the usual chromium-based oxidation reagents that have been used for the oxidation of cyclobutanols to cyclobutanones, for example, chromium(VI) oxide (Jones reagent),302 pyri-dinium chlorochromate,304 pyridinium dichromate,307 and chromium(YI) oxide/pyridine (Collins),303 are reported to do so without any serious problems. Alternatively, tetrapropylam-monium perruthenate in the presence of A-methylmorpholine A -oxide. oxalyl chloride in the presence of triethylamine in dimethyl sulfoxide (Swern),158,309,310 or phenyl dichlorophos-phate in the presence of triethylamine and dimethyl sulfoxide in dichloromethane (Pfitzner-Moffatt),308 can be used. The Pfitzner-Moffatt oxidation procedure is found to be more convenient than the Swern oxidation procedure, especially with respect to the strict temperature control that is necessary to achieve good yields in the latter, e.g. oxidation of 1 to give 2.308... 

Using chromium-based oxidants 2,4-Dimethylpentane-2,4-diol chromate(VI) diester, 122 Trimethylsilyl chlorochromate, 327 Using other oxidizing agents... 

Using chromium-based oxidants 2,4-Dimethylpentane-2,4-diol chromate(VI) diester, 122 Trimethylsilyl chlorochromate, 327 Using other oxidizing agents Bis(tributyltin) oxide, 41 Hydrogen hexachloroplatinate(IV)-Copper(II) chloride, 145 4-Methoxy-2,2,6,6-tetramethyl-1 -oxopiperidinium chloride, 183 Osmium tetroxide, 222 Potassium nitrosodisulfonate, 258 Samarium(II) iodide, 270 From alkenes by addition or cleavage reactions... 

In contrast to the amphoteric Cr(OH)3, chromium(II) hydroxide is a typical basic hydroxide. It dissolves in acid, but not in excess base. Conversely, the chromium(VI) compound, Cr02(0H)2, is a strong acid (chromic acid, H2Cr04). Recall from Section 15.15 that acid strength increases with increasing polarity of the O-H bonds, which increases, in turn, with increasing oxidation number of the chromium atom. 

Exposure of rats to sodium dichromate at 0.4 mg chromium(VI)/m3 for 90 days did not cause abnormalities, as indicated by histopathological examination of the kidneys. Serum levels of creatinine and urea and urine levels of protein were also normal (Glaser et al. 1985, 1990). Furthermore, no renal effects were observed in rats exposed to 0.1 mg chromium/m3 as sodium dichromate (chromium(VI)) or as a 3 2 mixture of chromium(VI) trioxide and chromium(III) oxide for 18 months, based on histological examination of the kidneys, urinalysis, and blood chemistry (Glaser et al. 1986, 1988). Rats exposed to 15.5 mg chromium(IV)/m3 as chromium dioxide for 2 years showed no histological evidence of kidney damage or impairment of kidney function, as measured by routine urinalysis. Serum levels of blood urea nitrogen, creatinine, and bilirubin were also normal (Lee et al. 1989). 

The amount of absorption of chromium(VI) and chromium(III) was measured in four male and two female volunteers (ages ranging from 25 to 39 years) treated orally with potassium chromate (chromium(VI)) or chromic oxide (chromium(III)) in capsules at doses of 0.005 mg/kg/day and 1.0 mg/kg/day, respectively (Finley et al. 1996b). Subjects were exposed to each compound for 3 days. Based on urinary excretion data, mean absorption of potassium chromate was 3.4% (range 0.69-11.9%). No statistically significant increase in urinary chromium was observed during chromic oxide dosing,... 

Many of the traditional oxidants are based on chromium) VI) compounds. These chromium reagents are highly toxic, and they are difficult to dispose of properly. Chemists are gradually moving to less toxic oxidants. We will cover the traditional chromium reagents and their uses, and then we will survey the more environmentally friendly alternatives. 

The most commonly used methods for oxidizing alcohols are based around metals in high oxidation states, often chromium(VI) or manganese(VII), and you will see that mechanistically they are quite similar—they both rely on the formation of a bond between the hydroxyl group and the metal. Another class of oxidations, those that use halogens, sulfur, or nitrogen in high oxidation states, we will deal with relatively briefly. 

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