Oxidation of carbonyl compounds

The oxidation of aldehydes to the corresponding carboxylic acids has been widely investigated and numerous procedures are known in aqueous and organic media [33]. Aromatic aldehydes have recently been oxidized at 0-4°C in aqueous performic acid produced by the addition of H2O2 to formic acid [34]. Generally, the carboxylic acid precipitates out of the reaction mixture and can be isolated simply by filtration. When heteroaromatic aldehydes such as formylpyridines, formylquinolines and formylazaindoles are oxidized, the formation of N-oxides is avoided. The use of cosolvents (tetrahydrofuran (THE), Af,A-dimethylformamide (DMF)) gives less satisfactory results. 

The formyl group can be chemoselectively oxidized, in the presence of other oxidizable functionalities, in aqueous media containing an equivalent amount of surfactant. For example, 4-(methylthio)benzaldehyde is quantitatively oxidized [35] to 4-(methylthio)benzoic acid with TBHP in a basic aqueous medium in the presence of (CTA)2S04 (cetyltrimethylammonium sulfate). 

Selective oxidative cleavage of a-diketones with peroxides is also a Baeyer-Villiger oxidation which produces acids via anhydrides. SPC in H20-acetone cleaves aromatic and aliphatic a-diketones to give the corresponding carboxylic acids in high yields [39]  

Oxidation of carbonyl compounds is an important area of oxidation and involves a variety of different reaction types. This area has been reviewed by Bolm in Chapter 9 of the book Modem Oxidation Methods (2004), and the present chapter is an update of this review. We have focused on two areas of carbonyl oxidation where important developments have occurred (i) oxidation of aldehydes to carboxylic adds and (ii) Baeyer-Villiger oxidation. 

The transformation of aldehydes to carboxylic acids is a fundamental reaction in organic synthesis. Many successful methods have been developed for these types of oxidations [1], but most of them have limitations as they require stoichiometric amounts of oxidants such as chlorite [2], diromium(VI) reagents [3], potassium permanganate [4], or peroxides [5]. The use of organic solvents e.g., acetonitrile, didiloromethane, cyclohexane, formic add, or benzene is also usually necessary. Despite the fact that these methods have several disadvantages, such as low selectivity and production of waste, some of them have been widely used in industry and are still in use today. The growing awareness of the environment has created a demand for efficient oxidation processes with environmentally friendly oxidants under mild conditions ( green chemistry) [6]. 

Molecular oxygen and hydrogen peroxide are desirable oxidants for these transformations, since they are inexpensive and environmentally friendly, with water as the only by-product. Therefore, various improved methodologies using molecular oxygen or hydrogen peroxide directly as the oxidants have been explored in recent years and reported in the literature. 

Aldehydes are more easily oxidized than ketones. Oxidation of an aldehyde gives a carboxylic acid with the same number of carbon atoms. 

Because the reaction occurs easily, many oxidizing agents, such as KMn04, Cr03, Ag20, and peracids (see eq. 8.18), will work. Specific examples are 

The symbol I indicates formation of a precipitate the symboi t indicates the formation of a gas. 

Silver ion as an oxidant is expensive but has the virtue that it selectively oxidizes aldehydes to carboxylic acids in the presence of alkenes (eq. 9.38). 

A laboratory test that distinguishes aldehydes from ketones takes advantage of their different ease of oxidation. In the Tollens silver mirror test, the silver-ammonia complex ion is reduced by aldehydes (but not by ketones) to metallic silver. The equation for the reaction may be written as follows  

In the Baeyer-Villiger reaction, ketones are treated with peracids to give carboxylic esters by the insertion of oxygen. A similar reaction of ketones is 

S5mthesis of carbojg lic ester from ketone employing aldehyde and diojg gen in the presence of copper catalyst. 

Examples for the oxidation of carbonyl compounds using halide ions as redox catalyst are listed in Table 4. No. 47-50. Thus, in the presence of alcohols, aldehydes are transformed to esters (No. 47) 

Quite unique is the formation of a-A,A-dialkylamino ketones from aldehydes and dialkylamines (Eq. (62) Table 4, No. 50) 

Aldehydes are oxidized easily by moist silver oxide or by potassium permanganate solution to the corresponding acids. The mechanism of the permanganate oxidation has some resemblance to the chromic acid oxidation of alcohols (Section 15-6B)  

Many aldehydes are oxidized easily by atmospheric oxygen in a radical-chain mechanism. Oxidation of benzenecarbaldehyde to benzenecarboxylic acid has been studied particularly well and involves formation of a peroxy 

The benzenecarbonyl radical, C6HsCO, then propagates a chain reaction. propagation 

The peroxy acid formed then reacts with benzenecarbaldehyde to give two molecules of carboxylic acid  

The oxidation of benzenecarbaldehyde with peroxybenzenecarboxylic acid (Equation 16-8) is an example of a reaction of wide applicability in which aldehydes are oxidized to carboxylic acids, and ketones are oxidized to esters. 

The TTN-KIO catalyst oxidises acetophenones to give methyl aryl acetates in high yields (e.g. equation 4.32) [134]. Conventional methods usually give low selectivity and poor yields [135]. 

Many oxidation reactions have been carried out using hydrogen peroxide and the titanosilicate, TS-1. However, this catalyst has relatively small pores and is therefore not an efficient catalyst for the oxidation of large molecules. This problem has been solved by the successful generation of a medium-pore titanium zeolite Beta-Ti [136]. Cyclododecane and cyclohexane are both oxidised selectively by H2O2 in the presence of the new titanium zeolite, favouring the ketone product. 

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The ff-oxidation of carbonyl compounds may be performed by addition of molecular oxygen to enolate anions and subsequent reduction of the hydroperoxy group, e.g. with triethyl phosphite (E.J. Bailey, 1962 J.N. Gardner, 1968 A,B). If the initially formed a-hydroperoxide possesses another enolizable a-proton, dehydration to the 1,2-dione occurs spontaneously, and further oxidation to complex product mitctures is usually observed. 

The electrochemical oxidation of carbonyl compounds is achieved by direct and indirect methods. 

Indirect oxidation of carbonyl compounds using mediators leads to better results than the direct oxidation. 

Sunden, H., Dahlin, N., Ibrahem, I., Adolfsson, H. and Cordova, A. Novel Organic Catalysts for the Direct Enantioselective a-Oxidation of Carbonyl Compounds. Tetrahedron Lett., 2005, 46, 3385-3389. 

Synthetically especially valuable is the oxidation of carbonyl compounds and nitroalkanes by manganese(III) salts to form carboxymethyl and nitromethyl radicals, respectively. These radicals can be trapped by olefins like 1,3-butadiene or aromatic compounds to yield synthetically interesting products. In this case it is very advantageous to generate and regenerate the oxidizing species in situ by indirect electrolysis. This was the basis for the development of a process for the synthesis of sorbic acid viay-vinyl-y-butyrolactone Equations (31)—(35) summarize the im-... 

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,... 

The oxidation of carbonyl compounds can be achieved with hypervalent iodine reagents quite easily. A general feature of these reactions is the electrophilic attack of the hypervalent iodine reagent at the a-carbon atom of a carbonyl group and a review on this chemistry has been published recently [6]. This leads to hypervalent iodine intermediates of type 55. These phenyliodinated intermediates are quite unstable and a variety of subsequent reactions are possible. Intermediates 55, Scheme 24, can be considered as umpoled substrates regarding the reactivity of the a-position of the initial carbonyl compounds. Major processes are the substitution by a nucleophile (see Sect. 3.5.1 Functionalization in the a-Position) or the introduction of a carbon-carbon double bond (see Sect. 3.5.2 Introduction of an a,/ -Unsaturation). 

Anodic Oxidation of Carbonyl Compounds 3.1.6.1 Kolbe Reaction... 

Oxidation of carbonyl compounds was interpreted by Malaprade as conforming to the a-glycol type by the assumption that the reaction proceeds through the hydrated form of the carbonyl group, >C(OH)2. This hypothesis is useful in interpreting the results of the oxidation of some complex compounds, intermediates of the type RCHOHCHO being oxidized like the a-glycols. 

An interesting method for the a-oxidation of carbonyl compounds leading to optically active a-hydroxy carboxylic acid derivatives has recently been developed... 

Oxidation reactions - notably alkene epoxidations - were some of the first asymmetric organocatalytic processes to develop into generally useful synthetic methods applicable to a range of substrates [1], This chapter surveys these reactions, with emphasis placed on the most practical and general. Some recent, very useful oxidation reactions involving a-oxidation of carbonyl compounds are covered elsewhere (see Chapter 2). 

R. M. Moriarty, O. Prakash, Oxidation of Carbonyl Compounds with Organohypervalent Iodine Reagents, Org. React. 1999, 54, 273 418. 

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