Oxidation of secondary alcohols to ketones

All oxidants used for the oxidation of primary alcohols to aldehydes can be applied to secondary alcohols. Because the products, ketones, are much less sensitive to overoxidation than aldehydes, more intensive reaction conditions, such as an excess of the oxidant, higher temperatures, or longer reaction times, can be used. Examples of oxidations of secondary alcohols to ketones are shown in equations 265-268. 

Catalytic dehydrogenation of volatile alcohols is carried out by passing their vapors over copper at 300 °C [344] or over copper chromite at 275-325 °C for 1.7-4 h, with yields ranging from 20 to 80% [554]. Dehydrogenation in the liquid phase is accomplished by refluxing the alcohol with copper chromite in xylene for 4 h [556] or by heating the alcohol in paraffin oil with Raney nickel and a catalytic amount of potassium hydroxide at 150-180 °C for 6 h. Thus endo-norborneol is transformed into norcamphor in 95% yield [928]. 

Secondary alcohols are converted into ketones in 70-98% isolated yields when refluxed with Raney nickel in benzene for 1-24 h with azeotropic removal of water [927]. The addition of 1-octene as a hydrogen acceptor does not affect the yields. Primary alcohols, under such reaction conditions, usually suffer decarbonylation and yield hydrocarbons vith one less carbon [927] (equation 240). 

A similar dehydrogenation is accomplished in 90-100% yield by passing vapors of the alcohol in a current of air (less than the stoichiometric amount) over a copper or, better still, silver catalyst at 350-400 °C [7]. 

Photooxidation of alcohols to ketones in high yields is performed at room temperature with oxygen in the presence of at least 1 mol of a base (Na, NaH, NaOH, KOH, or terr-BuOK) under irradiation with rose bengal as a sensitizer [45]. 

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A white solid, m.p. 178 C. Primarily of interest as a brominaling agent which will replace activated hydrogen atoms in benzylic or allylic positions, and also those on a carbon atom a to a carbonyl group. Activating influences can produce nuclear substitution in a benzene ring and certain heterocyclic compounds also used in the oxidation of secondary alcohols to ketones. 

Selective oxidation of secondary alcohols to ketones is usually performed with CrOj/HjSO, I I in acetone (Jones reagent) or with CrOjPyj (Collin s reagent) in the presence of acid-sensitive groups (H.G. Bosche, 1975 C. Djerassi, 1956 W.S. Allen, 1954). As mentioned above, a,)S-unsaturated secondary alcohols are selectively oxidized by MnOj (D.G. Lee, 1969 D. Arndt, 1975) or by DDQ (D. Walker, 1967 H.H. Stechl, 1975). 

Alcohols are oxidized slowly with PdCh. Oxidation of secondary alcohols to ketones is carried out with a catalytic amount of PdCh under an oxygen atmo-sphere[73.74]. Also, selective oxidation of the allylic alcohol 571 without attacking saturated alcohols is possible with a stoichiometric amount of PdfOAc) in aqueous DMF (1% H OifSll],... 

Oppenauer reaction is oxidation of secondary alcohols to ketones using aluminium t-butoxide... 

Oxidation of secondary alcohols to ketones (Section 15.10) Many oxidizing agents are available for converting secondary alcohols to ketones. PDC or PCC may be used, as well as other Cr(VI)-based agents such as chromic acid or potassium dichromate and sulfuric acid. 

Secondary alcohol oxidases catalyze the oxidation of secondary alcohols to ketones using molecular oxygen as oxidant. A secondary alcohol oxidase from polyvinyl alcohol-degrading bacterium Pseudomonas vesicularis var. povalolyticus PH exhibited activity toward several... 

N-bromosuccinimide is a selective oxidising agent and oxidises OH groups without disturbing other oxidisable groups. Thus while it does not oxidise aliphatic primary alcohols in presence of water it is highly selective for the oxidation of secondary alcohols to ketones. 

Thioanisolc. A system utilizing thio-anisole as an organic mediator was developed for the oxidation of secondary alcohols to ketones (Fig. 5 2-octanol to 2-octanone 99%, menthol to menthone 92%, cyclododecanol to cyclododecanone 75%) [43]. The use of 2,2,2-trifluoroethanol as a solvent in the mediatory system improved the yields [44]. 

Hydrogen transfer reactions from an alcohol to a ketone (typically acetone) to produce a carbonyl compound (the so-caUed Oppenauer-type oxidation ) can be performed under mild and low-toxicity conditions, and with high selectivity when compared to conventional methods for oxidation using chromium and manganese reagents. While the traditional Oppenauer oxidation using aluminum alkoxide is accompanied by various side reactions, several transition-metal-catalyzed Oppenauer-type oxidations have been reported recently [27-29]. However, most of these are limited to the oxidation of secondary alcohols to ketones. 

P. E. Morris, D. E. Kiely, Ruthenium Tetraoxide Phase-Transfer-Promoted Oxidation of Secondary alcohols to Ketones, J. Org. Chem. 52 (1987) 1149-1152. 

The nickel oxide electrode is generally useful for the oxidation of alkanols in a basic electrolyte (Tables 8.3 and 8.4). Reactions are generally carrried out in an undivided cell at constant current and with a stainless steel cathode. Water-soluble primary alcohols give the carboxylic acid in good yields. Water insoluble alcohols are oxidised to the carboxylic acid as an emulsion. Short chain primary alcohols are effectively oxidised at room temperature whereas around 70 is required for the oxidation of long chain or branched chain primary alcohols. The oxidation of secondary alcohols to ketones is carried out in 50 % tert-butanol as solvent [59], y-Lactones, such as 10, can be oxidised to the ketoacid in aqueous sodium hydroxide [59]. 

There are some reports of kinetic investigations of Ru-catalysed oxidations in which the nature of the active catalyst or catalyst precursor is unclear but which may be predominantly [RuO ] . Two papers used electronic or Raman spectroscopy to identify such species [212], [222]. Examples in which [RuO ]" has been shown to be the active species or catalyst precursor in the oxidation of secondary alcohols to ketones include... 

Most Ru-catalysed oxidations of secondary alcohol to ketone steps involve TPAP one that does not is a stage in the industrial preparation of the inhibitor thrombin, which used RuClj/aq. Na(Br03)/CH3CN [166],... 

A new, selective and efficient alternative method has been developed for the oxidation of secondary alcohols to ketones in moderate to good yields in hydrated media. Table 5.3 shows different substrates that can be selectively oxidized under the reaction conditions. 

If the cation introduced by ion exchange is capable of multiple valence, the clay may serve as a catalyst for oxidation or reduction reactions. For example, montmorillonite treated with iron(III) nitrate is so reactive that it has to be stored under an inert atmosphere the clay catalyzes reactions of the nitrate ion, such as oxidation of secondary alcohols to ketones (via nitrite ester intermediates) and organic hydrazides to azides, and the nitration of phenols. 

A recent report (J. Org. Chem. 2004, 69, 8510) by Paul G. Williard of Brown University and Ruggero Curci of University di Bara of the oxidation of 5 to 6 serves as a timely reminder that the widely-used epoxidation reagent dimethyl dioxirane is also useful for the oxidation of secondary alcohols to ketones. 

Table 7. Oxidation of secondary alcohols to ketones at the nickel hydroxide electrode...

Oxidation of alcohols.1 Os04 is comparable to Ru04 for oxidation of secondary alcohols to ketones. It oxidizes primary alcohols only to the corresponding aldehydes in fact primary alcohols can be oxidized with fair selectivity in the presence of secondary alcohols. 

Some successful oxidations of secondary alcohols to ketones, using Jones reagent, are listed bellow ... 

Ru04 is a very reactive reagent that is employed not only for the oxidation of secondary alcohols to ketones and primary alcohols to carboxylic acids,36 but also to perform the following transformations ... 

One of die most common methods for the preparation of ketones is by the oxidation of secondary alcohols. The use of chromic acid (Jones reagent) is easy, safe, and effective for the oxidation of secondary alcohols to ketones. Furthermore Jones reagent gives a nearly neutral solution and thus can be used with a variety of acid-sensitive functional groups. 

Sodium hypochlorite (household bleach) and acetic acid offers a very cheap and effective alternative to Jones reagent for the oxidation of secondary alcohols to ketones and has been widely used for the synthesis of ketones. 

There are many other reported methods for the oxidation of secondary alcohols to ketones in fact, over 140 different methods are listed in Comprehensive Organic Transformations by Larock. However, few are as versatile and useful as those listed above. 

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