Oxidation of Alcohols to Aldehydes, Ketones, and Carboxylic Acids

Oxidation of Alcohols to Aldehydes, Ketones, and Carboxylic Acids 

Alcohols with at least one hydrogen attached to the hydroxyl-bearing carbon can be oxidized to carbonyl compounds. Primary alcohols give aldehydes, which may be further oxidized to carboxylic acids. Secondary alcohols give ketones. Notice that as an 

Tertiary alcohols, having no hydrogen atom on the hydroxyl-bearing carbon, do not undergo this type of oxidation. 

A common laboratory oxidizing agent for alcohols is chromic anhydride, Cr03, dissolved in aqueous sulfuric acid (Jones reagent). Acetone is used as a solvent in such oxidations. Typical examples are 

Jones le nt is an oxidizing agent composed of Cr03 dissolved in aqueous H2SO4. 

The widely used Moffatt-Pfitzner oxidation works with in situ formed adducts of dimethyl sulfoxide with dehydrating agents, e.g DCC, AcjO, SO], P4C) o, COQ2 (K.E. Pfitzner, 1965 A.H. Fenselau, 1966 K.T. Joseph, 1967 J.G. Moffett, 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. 

Swem oxidation OCOCOC1/DMSO (EIjN/CHQi) H 

The Dess-Manin periodinane ( DMP ) reagent, l,l,l-tris(acetyloxy)-l,l-dihydro-l,2-benziodoxol-3(lff)-one, has also been used in several complex syntheses for the oxidation of primary or secondary alcohols to aldehydes or ketones, respectively (e.g., M. Nakatsuka, 1990). It is prepared from 2-iodobenzoic acid by oxidation with bromic acid and acetylation (D. B. Dess, 1983). 

The conversion of primary alcohols and aldehydes into carboxylic adds is generally possible with all strong oxidants. Silverfll) oxide in THF/water is particularly useful as a neutral oxidant (E.J. Corey, 1968 A). The direct conversion of primary alcohols into carboxylic esters is achieved with Mn02 in the presence of hydrogen cyanide and alcohols (E.J. Corey, 1968 A,D). The remarkably smooth oxidation of ethers to esters by ruthenium tetroxide has been employed quite often (D.G. Lee, 1973). Dibutyl ether affords butyl butanoate, and tetra-hydrofuran yields butyrolactone almost quantitatively. More complex educts also give acceptable yields (M.E. Wolff, 1963). 

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Recently, great advancement has been made in the use of air and oxygen as the oxidant for the oxidation of alcohols in aqueous media. Both transition-metal catalysts and organocatalysts have been developed. Complexes of various transition-metals such as cobalt,31 copper [Cu(I) and Cu(II)],32 Fe(III),33 Co/Mn/Br-system,34 Ru(III and IV),35 and V0P04 2H20,36 have been used to catalyze aerobic oxidations of alcohols. Cu(I) complex-based catalytic aerobic oxidations provide a model of copper(I)-containing oxidase in nature.37 Palladium complexes such as water-soluble Pd-bathophenanthroline are selective catalysts for aerobic oxidation of a wide range of alcohols to aldehydes, ketones, and carboxylic acids in a biphasic... 

Common alcohol oxidation methods employ stoichiometric amounts of toxic and reactive oxidants like Cr03, hypervalent iodine reagents (Dess-Martin) and peracids that pose severe safety and environmental hazards in large-scale industrial reactions. Therefore, a variety of catalytic methods for the oxidation of alcohols to aldehydes, ketones or carboxylic acids have been developed employing hydrogen peroxide or alkyl hydroperoxides as stoichiometric oxygen sources in the presence of catalytic amounts of a metal catalyst. The commonly used catalysts for alcohol oxidation are different MoAV(VI), Mn(II), Cr(VI), Re(Vn), Fe(II) and Ru complexes . A selection of published known alcohol oxidations with different catalysts will be presented here. 

The oxidation of alcohols to aldehydes, ketones or carboxylic acids is one of the commonest reactions in organic chemistry, and is frequently achieved by transition metal complexes or salts. However, in most cases the precise mechanisms are not known, and the intermediates not fully characterised. In general, metal complexes of the alcohols are formed as transient intermediates in these reactions, but we shall not deal with these extremely important reactions in any great detail. The precise mechanisms depend upon the accessibility of the various one- and two-electron reduction products of the particular metal ion which is involved in the reaction. However, we will outline a brief indication of the mechanism. The first step involves the formation of an alcohol complex of the metal ion (Fig. 9-14). This might or might not deprotonate to the alkoxide form, depending upon the pH conditions of the reaction, the pK of the alcohol and the polarising ability of the metal ion. 

A number of systems consist of a palladium salt, typically PdCb or Pd(OAc)2, with abase. For example, PdCb-NaOAc catalyzes the aerobic oxidation of secondary alcohols in ethylene carbonate under nuld conditions. Sheldon has carried out mechanistic investigations on a number of related Pd systems and shown that water-soluble complexes of Pd(II) with phenanthrohnes are stable, recyclable catalysts for the selective aerobic oxidation of a wide range of alcohols to aldehydes, ketones, and carboxylic acids in a biphasic liquid liquid system. The active catalyst is a dihydroxy-bridged palladium dimer. 

The use of oxoammonium ions such as those derived from TEMPO in combination with inexpensive, safe, and easy-to-handle terminal oxidants in the conversion of alcohols into aldehydes, ketones, and carboxylic acids is a significant example of how it is possible to develop safer and greener chemistry, by avoiding the use of environmentally-unfriendly or toxic metals. However, separation of the products from TEMPO can be problematic, especially when the reactions are run on... 

The functions of flavoprotein enzymes are numerous and diversified.151-1533 A few of them are shown in Table 15-2 and are classified there as follows (A) oxidation of hemiacetals to lactones, (B) oxidation of alcohols to aldehydes or ketones, (C) oxidation of amines to imines, (D) oxidation of carbonyl compounds or carboxylic acids to a,(3-unsaturated compounds,... 

Aerobic oxidation of alcohols to the corresponding aldehydes, ketones, and carboxylic acids can be performed in aqueous solution by using noble metals as catalysts under mild conditions, but severe deactivation of the catalysts often occurs, seriously limiting process development [5b, c, e]. 

The oxidation of alcohols to aldehydes or ketones by periodane has several advantages over chromium and DMSO-based oxidants because of its shorter reaction times, higher yields and simplified work up. There is very little overoxidation to the carboxylic acid. It is a practical reagent for the facile and efficient oxidation of benzylic and allylic alcohols. Saturated alcohols are slow in their reactions with it. It oxidizes alcohols in the presence of non-hydroxylic functional groups such as sulfides, enols, ethers, furans and 2°-amides. An example of the DMP oxidation is the oxidation of 3,4,5-trimethoxybenzyl alcohol (7.17) with 7.16 in CH2CI2 to give 94% yield of 3,4,5-trimethoxybenzaldehyde (7.18). 

The compound that is formed by oxidation of an alcohol depends upon the number of hydrogens attached to the carbon bearing the —OH group, that is, upon whether the alcohol is primary, secondary, or tertiary. We have already encountered these products—aldehydes, ketones, and carboxylic acids—and should recognize them from their structures, even though we have not yet discussed much of their chemistry. They are important compounds, and their preparation by the oxidation of alcohols is of great value in organic synthesis (Secs. 16.9 and 16.10). 

The ease with which alcohols are oxidized to aldehydes, ketones, or carboxylic acids (depending on the alcohol that you start with and the conditions that you employ), coupled with the ready availability of alcohols, provides the pathway necessary to many successful s)mthetic transformations. For example, let s develop a method for synthesizing ethyl propanoate, using any inorganic reagent you wish but limiting yourself to organic alcohols that contain three or fewer carbon atoms ... 

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