Alcohol to Ketone Oxidation State

Activated manganese dioxide (Mn02) reliably oxidizes acetylenic, allylic, and benzylic alcohols to aldehydes and ketones. Saturated primary and secondary alcohols are also oxidized, albeit more slowly. The two main concerns are the activity of the manganese dioxide and the slow filtration of salts after the reaction. Activated Mn02 is available commercially or may be prepared. 

To a solution of 15.3 g (37.5 mmol) of the alcohol in 150 mL of hexanes was added 60 g of activated Mn02. The reaction mixture was stirred at 22 °C overnight and filtered, and the solid residue was washed with 30% EtOAc in hexanes solution. The combined filtrates were dried (Na2S04) and concentrated in vacuo. The residue was purified by chromatography on Si02 (EtOAc hexanes, 1 10) to give 13.7 g (90%) of the ketone as a colorless oil. 

Chromium-based oxidations are reliable and well established, but the toxicity associated with chromium salts have meant that they are generally considered the 

Methyl oleandroside (7.10 g, 40.4 mmol, 1.0 equivalents) in CH2C12 (200 mL) was treated with 3 A powdered molecular sieves (20 g) and pyridinium dichromate (PDC 16.7 g, 44.3 mmol, 1.1 equivalents) at 2 °C followed by the addition of AcOH (4.0 mL). The mixture was warmed and stirred for 2 h at 25 °C. The mixture was treated with Celite (20 g), stirred for 30 min, and filtered. The solution was evaporated to a dark oil. 

Most aliphatic alcohols react slowly if at all with 2,3-dichloro-5,6-dicyano-p-benzo-quinone (DDQ), allowing selective allylic or benzylic alcohol oxidation. 

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In addition, it was shown that CuS0,(H20)- mixed with the KMnO, accelerated the oxidation of secondary alcohols. The combination produced an oxidant which was capable of oxidizing alcohols to ketones in high yield and under mild conditions as shown in Table I. Perhaps the most useful feature of the reactions in Table I is the easy workup filtration of the solids and evaporation of the benzene give the product in a satisfactory state of purity. 

Many other metabolic degradation pathways are either initiated by reactions involving generation of transient carbocations or pass through a transition state with highly positive charge density on a carbon center. Reactions in this category are the acidic hydrolysis of acetals, aminals, or enol ethers, and the oxidation of alcohols to ketones via a hydride-transfer mechanism. 

Pyridinium Chlorochromate. The need for improved oxidation of primary alcohols and greater ease for isolation of products prompted further research into the nature of Cr(VI) reagents. Corey found that addition of pyridine to a solution of chromium trioxide in aqueous HCl allowed crystallization of a solid reagent characterized as 31, pyridinium chlorochromate (PCC). This reagent was superior for the conversion of primary alcohols to aldehydes in dichloromethane but less efficient than the Collins oxidation when applied to allylic alcohols. Oxidation of 1-heptanol with PCC in dichloromethane gave 78% of heptanal, for example. As stated by Corey, PCC is an effective oxidant in dichloromethane although aqueous chlorochromate species are not very effective oxidants. Oxidation of secondary alcohols to ketones is straightforward, as in Banwell s synthesis of y-lycorane, in which 32 was oxidized by PCC to the ketone (33). ... 

Steric Effects.—The consequences upon chemical reaction of non-bonded interactions between enantiomeric pairs of molecules have been discussed an antipodal interaction effect was observed in a reductive camphor dimerization and in a camphor reduction. The full paper on the correlation of the rates of chromic acid oxidation of secondary alcohols to ketones with the strain change in going from the alcohol to the carbonyl product has now appeared. It is concluded that the properties of the product are reflected in the transition state for the oxidation. High yields of hindered carbonyls are available from the corresponding alcohols by reaction with DMSO and trifluoroacetic anhydride (TFAA) indeed, the more hindered the alcohol, the higher the yield of carbonyl compound reported Since the DMSO-TFAA reaction occurs instantaneously at low temperatures (<—50°C), it is possible to oxidize alcohols that form stable sulphonium salts only at low temperature. Thus, ( )-isoborneol reacts at room temperature to give camphene, the product of solvolysis of the sulphonium salt the oxidation product, ( + )-camphor, was obtained by the addition of base at low temperature. 

Pyridinium chiorochromate (PCC) is a popular reagent for the selective oxidation of primary alcohols to aldehydes and secondary alcohols to ketones. PCC is prepared commercially by the reaction of pyridine with hydrochloric acid in the presence of chromium trioxide (CrOg). The chromium atom in both CrOg and also in PCC is in the 6-I- oxidation state (orange color). 

Many of the preferred reagents for the oxidation of primary alcohols to aldehydes (secondary alcohols to ketones) contain the transition metal chromium in its highest oxidation state, VI. Upon reaction with an alcohol, the yellow-orange chromium(VI) species is reduced to the blue-green chromium(III) state. Normally the reaction is carried out in aqueous acid solution using the sodium dichromate salt, Na2Cr207, or the oxide, CrOs. A typical reaction is shown here ... 

One example is reported in which the oxidant N2O was in a supercriheal state (Tcrit = 36.4°C, Peril = 71.5 bar, perit = 0.452 g/cm ). Its critical data are similar to those for CO2 and N2O might be an attrachve oxidant as N2 is the only by-product. It was possible to oxidise phosphines to phosphine oxide without a catalyst below 100 C. Compounds with other funchonal groups remain unoxidised while in SCN2O soluhon. With a Pt/C catalyst, it became feasible to oxidise secondary alcohols to ketones, e.g. isobomeol to campher with 100% yield. ... 

Aldehydes are formed by the reduction of the ester of the corresponding acid to the alcohol, and then oxidising the alcohol with heated copper as catalyst. It is well known that when primary alcohols in the gaseous state are passed over finely-divided copper dust, obtained by reduction of copper oxide, at 250° to 400°, they yield hydrogen, and aldehydes or ketones respectively. 

The question about the competition between the homolytic and heterolytic catalytic decompositions of ROOH is strongly associated with the products of this decomposition. This can be exemplified by cyclohexyl hydroperoxide, whose decomposition affords cyclo-hexanol and cyclohexanone [5,6]. When decomposition is catalyzed by cobalt salts, cyclohex-anol prevails among the products ([alcohol] [ketone] > 1) because only homolysis of ROOH occurs under the action of the cobalt ions to form RO and R02 the first of them are mainly transformed into alcohol (in the reactions with RH and Co2+), and the second radicals are transformed into alcohol and ketone (ratio 1 1) due to the disproportionation (see Chapter 2). Heterolytic decomposition predominates in catalysis by chromium stearate (see above), and ketone prevails among the decomposition products (ratio [ketone] [alcohol] = 6 in the catalytic oxidation of cyclohexane at 393 K [81]). These ions, which can exist in more than two different oxidation states (chromium, vanadium, molybdenum), are prone to the heterolytic decomposition of ROOH, and this seems to be mutually related. 

Halogens are frequently used as oxidation agents and, under two-phase conditions, they can either be employed as ammonium complex halide salts [3], or in the molecular state with or without an added quaternary ammonium catalyst [4]. Stoichiometric amounts of tetra-n-butylammonium tribromide under pH controlled conditions oxidize primary alcohols and low-molecular-weight alkyl ethers to esters, a,cyclic ethers produce lactones [3], and secondary alcohols yield ketones. Benzoins are oxidized to the corresponding benzils (80-90%) by the tribromide salts in acetonitrile in the presence of benzoyl peroxide [5]. 

The cyde is central to the oxidation of any fuel that yields acetyl CoA, induding glucose, fritty acids, ketone bodies, ketogenic amino acids, and alcohol There is no hormonal control of the cyde, as activity is necessary irrespective of the fed or fasting state. Control is exerted by the energy status of the cell. 

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