Oxidation of Hydroxy Ketones to Diketones

Oxidations of hydroxy ketones to diketones occur frequently in steroidal alcohols. If the alcoholic group, usually secondary, is remote enough from the keto group, its oxidation takes place independently and is achieved by the same reagents that are used for the oxidation of alcohols. A solution of chromium trioxide in aqueous sulfuric acid oxidizes 5-pregnen-3p-ol-20-one in acetone solution at room temperature within 2-5 min to 5-pregnen-3,20-dione in 90% yield [579]. Similarly, lip-hydroxytestosterone 17-acetate is transformed by chromium trioxide in 80% acetic acid at room temperature in 30 min into 11-ketotestosterone 17-acetate in 92% yield [807]. 

A reagent suitable for oxidations of steroidal hydroxy ketones to diketones is dimethyl sulfoxide in the presence of various activators. It converts testosterone into 4-androstene-3,17-dione in 95-100% yields (equation 445) [1016, 1018], 

Oxidations of steroidal keto alcohols to diketones are frequently accomplished biochemically. In addition, isomerization of double bonds, dehydrogenations, and hydroxylations often take place. 

Dehydroandrosterone [1088] and dehydroepiandrosterone [1056] are converted by bacterium-infected yeast and Corynebacterium simplex ATCC 6946 into 4-androstene-3,17-dione in 87 and 55% yields, respectively (equation 446) [1056]. 

When the hydroxyJic group is in an a position with respect to the keto group, as in acyloins, oxidation to a-diketones is easily accomplished by many oxidants. 

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Triazines can be prepared by the condensation of amidrazones with diketones or of hydrazides with 2-halo-ketones. It is convenient to oxidize 2-hydroxy-ketones to the dicarbonyl component with manganese(IV) oxide, in the presence of the amidrazone, to produce the heterocycles. Hydrazides can also be utilized with 1,2-diketones, by including an ammonia source in the reagent mix. ... 

DMSO, molybdenum peroxide, benzene, reflux, 7-20 h, 60% yield. This method was used to m onoprotect 1,2-diols. The method is not general because oxidation to a-hydroxy ketones and diketones occurs with some substrates. On the basis of the mechanism and the results it would app>ear that overoxidation has a strong conformational dependence. 

Symmetrical and unsymmetrical benzoins have been rapidly oxidized to benzils in high yields using solid reagent systems, copper(II) sulfate-alumina [105] or Oxone-wet alumina [105, 106] under the influence of microwaves (Scheme 6.32). Conventionally, the oxidative transformation of a-hydroxy ketones to 1,2-diketones is accomplished by reagents such as nitric acid, Fehling s solution, thallium(III) nitrate (TTN), ytterbium(III) nitrate, ammonium chlorochromate-alumina and dayfen. In addition to the extended reaction time, most of these processes suffer from drawbacks such as the use of corrosive acids and toxic metals that generate undesirable waste products. 

Chain degradation proceeds at the oxidised sites, where two different routes can be discerned. One way uses the p-hydroxy ketone functionalities introduced by the initial enzymatic attack as direct substrates in an aldolase-like scission reaction. The other way proceeds via further oxidation of this structure to a 1,3-diketone, which serves as a target structure for a hydrolase-type splitting enzyme. 

The reagent is effective for oxidative cleavage of a-glycols to aldehydes, of a-hydroxy ketones to an aldehyde and a carboxylic acid, and of a-diketones and a-keto iicids to acids.3... 

Products detected or isolated from these oxidations include the corresponding a-hydroxy ketone and a-diketone and also adipic acid (from cyclohexanone) in up to 95 % yield. However, IrCI gives a-chloroketone in quantitative yield . Evidently when the rate of oxidation exceeds enolisation attack is on the keto form, probably via a complex, although this is definite only for Ce(IV) perchlorate, to give a radical, e.g. 

Oxidation of p-hydroxy ketones. Reaction of the Corey-Kim reagent with these substrates can result in dimethylsulfonium dicarbonylmethylides in 80-98% yield. These S-ylides are desulfurized to p-diketones by zinc in acetic acid, p-... 

Preparation and phytochemical reduction of 2,2 -thenoin and 2,2 -thenil have been studied in the authors laboratory (20a). It has been shown that 2,2 -thenoin gives a color reaction similar to that shown by benzoin and other acyloin condensation products in- the presence of alcoholic alkali. The hydroxy ketone may be oxidized by iodine in the presence of sodium methoxide to give the diketone, 2,2 -thenil, in excellent yields. Phytochemical reduction was shown also to be applicable to both compounds. It is significant that thenoin differs from benzoin, since reduction products were not obtained enzymatically from the latter. 

Permanganate oxidations may be used for the direct conversion of olefins to a-hydroxy ketones and 1,2-diketones in moderate yields usually under acidic conditions.562"566... 

Oxidation of alkenes.1 A well-ground mixture of KMn04/CuS04-5H20 (2 1) suspended in CH2C12 containing a trace of f-BuOH/H20 effects oxidation of alkenes at 25° to a-diketones or a-hydroxy ketones in modest to high yield. The r-BuOH/ H20 solvent is usually crucial for successful oxidation. In some cases, epoxides are the major products. 

Bridgehead bicyclic cyclopropanols or cyclopropyl silyl ethers 103 (R=H) cleaved to ring-expanded mixtures of cyclic (1-hydroxy ketones 105 and (1-diketones 106 in good overall yields catalyzed by 10 mol% of VO(acac)2 in the presence of oxygen (Fig. 32) [191, 192]. With 3-substituted substrates 103 (R=Me), mixtures of bicyclic endoperoxide hemiketals 104B and (1-hydroxy ketones 105 arose. In separate experiments it was shown that 105 is not oxidized to 106 under the reaction conditions, and thus the products most likely form from... 

Primary benzylic alcohols (equation 10) can be oxidized in the presence of saturated primary alcohtris using a catalyst derived from ammonium cerium(IV) nitrate supported on charcoal with air as the cooxidant (under these conditions a-hydroxy ketones are oxidized to a-diketones). ... 

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