The Oppenauer oxidation

Secondary alcohols may be oxidised to the corresponding ketones with aluminium ferf.-butoxlde (or tsopropoxlde) In the presence of a large excess of acetone. This reaction Is known as the Oppenauer oxidation and Is the reverse of the Meerweln - Ponndorf - Verley reduction (previous Section) it may bo expressed  

Acetone in conjunction with benzene as a solvent is widely employed. With cyclohexanone as the hydrogen acceptor, coupled with toluene or xylene as solvent, the use of higher reaction temperatures is possible and consequently the reaction time is considerably reduced furthermore, the excess of cyclohexanone can be easily separated from the reaction product by steam distillation. At least 0 25 mol of alkoxide per mol of alcohol is used however, since an excess of alkoxide has no detrimental effect 1 to 3 mols of aluminium alkoxide is recommended, particularly as water, either present in the reagents or formed during secondary reactions, will remove an equivalent quantity of the reagent. In the oxidation of steroids 50-200 mols of acetone or 10-20 mols of cyclohexanone are generally employed. 

The reaction is illustrated by the preparation of cholestenone from cholesterol the double bond migrates from the Py to the ap position during the oxidation  

The following mechanism appears reasonable (compare Section VI, 12), It assumes that the function of the aluminium ieri.-butoxide, or other alkoxide. is to provide a source of aluminium ions and that the aluminium salt of the secondary alcohol is the actual reactant. Aluminium with its sextet of electrons has a pronounced tendency to accept a pair of electrons, thus facilitating the initial coordination and the subsequent transfer of a hydride ion  

OXIDATION OF UNSATURATED COMPOUNDS WITH OZONISED OXYGEN (OZONOLYSIS) 

Aluminium tert.-butoxide. In a 500 ml. round-bottomed flask 

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The widely used Moifatt-Pfltzner oxidation works with in situ formed adducts of dimethyl sulfoxide with dehydrating agents, e.g. DCC, AcjO, SO], P4O10, CCXTl] (K.E, Pfitzner, 1965 A.H. Fenselau, 1966 K.T. Joseph, 1967 J.G. Moffatt, 1971 D. Martin, 1971) or oxalyl dichloride (Swem oxidation M. Nakatsuka, 1990). A classical procedure is the Oppenauer oxidation with ketones and aluminum alkoxide catalysts (C. Djerassi, 1951 H. Lehmann, 1975). All of these reagents also oxidize secondary alcohols to ketones but do not attack C = C double bonds or activated C —H bonds. 

Most terpene-based citral (5) produced is based on the catalytic oxidative dehydrogenation of nerol (47) and geraniol (48), or by the Oppenauer oxidation of nerol and geraniol (123—125). 

The oxidation of a hydroxyl group by an aluminum alkoxide-catalyzed hydrogen exchange with a receptor carbonyl compound is known as the Oppenauer oxidation. For oxidation of steroidal alcohols the reaction is generally... 

The Oppenauer oxidation has found considerable application in steroid chemistry since it is the most convenient method for converting the commonly... 

The reduction of ketones to secondary alcohols and of aldehydes to primary alcohols using aluminum alkoxides is called the Meerw>ein-Ponndorf-Verley reduction. The reverse reaction also is of synthetic value, and is called the Oppenauer oxidation. ... 

As a synthetic method however the Oppenauer oxidation is of limited importance. 

Isopropyl Alcohol and Aluminum Isopropoxide. This is called the Meer-wein-Ponndotf-Verley reduction It is reversible, and the reverse reaction is known as the Oppenauer oxidation (see 19-3) ... 

The Oppenauer Oxidation. When a ketone in the presence of base is used as the oxidizing agent (it is reduced to a secondary alcohol), the reaction is known as the Oppenauer oxidation. This is the reverse of the Meerwein-Ponndorf-Verley reaction (16-23), and the mechanism is also the reverse. The ketones most commonly used are acetone, butanone, and cyclohexanone. The most common base is aluminum r r/-butoxide. The chief advantage of the method is its high selectivity. Although the method is most often used for the... 

The Oppenauer oxidation makes use of ketones (typically acetone) or alkenes as hydrogen acceptors and this absence of a strong oxidising agent allows to overcome some potential NHC oxidative instability. Reactions consist of an equilibrium between an alcohol and its oxidised form (Scheme 10.9). 

There are also reactions in which hydride is transferred from carbon. The carbon-hydrogen bond has little intrinsic tendency to act as a hydride donor, so especially favorable circumstances are required to promote this reactivity. Frequently these reactions proceed through a cyclic TS in which a new C—H bond is formed simultaneously with the C-H cleavage. Hydride transfer is facilitated by high electron density at the carbon atom. Aluminum alkoxides catalyze transfer of hydride from an alcohol to a ketone. This is generally an equilibrium process and the reaction can be driven to completion if the ketone is removed from the system, by, e.g., distillation, in a process known as the Meerwein-Pondorff-Verley reduction,189 The reverse reaction in which the ketone is used in excess is called the Oppenauer oxidation. 

The reversible reduction of aldehydes or ketones to the corresponding alcohols using aluminum alkoxides such as aluminum isopropoxide (Al[OCH(CH3)2]3), the reducing alcohol usually being isopropyl alcohol (Le., RCOR + CH3CH(0H)CH3 RCH(OH)R + CH3C0CH3). The reaction is facilitated by the removal of acetone by distillation". This reaction has served as a model for metal-ion-dependent hydride transfer reactions catalyzed by certain enzymes. The reverse reaction is known as the Oppenauer oxidation . ... 

The oxidation of 2-ethylhexan-l-ol to 2-ethyl-hexanal by the Oppenauer oxidation with aliphatic aldehydes such as acetaldehyde, propionaldehyde, and isobutyr-aldehyde has been investigated with gas-phase reactants and MgO as the catalyst (196). Reaction with propionaldehyde was found to be an effective synthetic route for 2-ethylhexanal preparation, whereas with acetaldehyde and isobutyraldehyde a gradual catalyst deactivation in a flow reactor was observed. 

In steroidal alcohols the 3a- or 3P-hydroxy group (18, Table 10) is selectively oxidized in the presence of the 17P-hydroxy group. The yield obtained corresponds to that of the Oppenauer-oxidation which is the most selective oxidation method for the 3-OH group. 

The selective oxidation of the 3P-hydroxy group in the presence of lip- and 20p-hydroxy groups in the triol 25 is unprecedented. In the Oppenauer-oxidation of similar compounds the 3P-OH group is oxidized in only 30% yield The remarkable selectivity obtained may be due to the fact that the 20p-hydroxy group is placed on the P-side of the steroid, remote from the electrode, which probably attacks from the less hindered a-side. 

The reverse reaction is known as the Oppenauer oxidation. Here aluminium tri tertiary but oxide and an involatile ketone such as cyclohexanone are used to oxidise any secondary alcohol to the corresponding ketone. 

The Oppenauer oxidation of cholesterol to A4-cholesten-3-one of m.p. 77-79° in 70-93% yield has been reported in these volumes.10 Isomerization of As-cholesten-3-one by a mineral acid or a base has been conducted satisfactorily only on a micro scale 6 the method of isomerization with oxalic acid has been reported.3... 

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